PMID- 8490533 TI - Biomechanical analysis of the Cotrel-Dubousset spine internal fixator in different load conditions. AB - The aim of the present research is to analyse the mechanical behaviour of the Cotrel-Dubousset spine internal fixator using numerical and experimental techniques. Simple experimental and numerical models of a spine section (four vertebrae of the thoraco-lumbar region) were developed in order to evaluate the response of the system, particularly the stress-strain state in the rods, by means of strain-gauge measurements. The system was subjected to combined compressive and bending static loading and the deformations of the system were measured on models simulating physiological and pathological conditions, with and without the fixator. PMID- 8490534 TI - Micron-size particles emission from bioceramics induced by pulsed laser deposition. AB - Pulsed laser deposition of hydroxyapatite is applied to cover titanium medical prosthesis. Laser irradiation of ceramics by power-pulsed ruby laser produces high velocity micron-size particles emission with a narrow ejection plume directed normally to the target surface. Photoemitted particles are deposited on a metal surface at 400 degrees C to obtain a granular film, stoichiometric, polycrystalline, and very adherent to the substrate. Deposited films are highly biocompatible and may be used to induce osteointegration processes of the implanted prosthesis with the bone tissues. The comparison between laser and plasma spray depositions of bioceramics is discussed. PMID- 8490536 TI - Molecular oncology: from basic research towards clinical application. PMID- 8490535 TI - Hemocompatibility of diamond-like carbon coating. AB - The new prosthetic heart valve that has been designed by FII Company and Pr. Baudet involves a new "composite" material: titanium alloy T16A14V coated with Diamond-like Carbon. The purpose of this study was to evaluate the in vitro hemocompatibility of this new material in terms of protein adsorption and platelet retention. The static protein adsorption test gave interesting results, particularly for the albumin assay (237%) compared to the results obtained with a silicone elastomer chosen as a reference; the fibrinogen quantity, adsorbed on the surface of the material was slightly higher than that adsorbed on the silicone surface. Platelets adhere quite twice as much as they do on the reference surface. Such investigations showed good hemocompatibility results and should initiate further studies. PMID- 8490537 TI - Platelet-derived growth factor and risk factors for colorectal cancer. AB - Platelet-derived growth factor (PDGF) is a potent mitogen for a variety of cells. Abnormal PDGF activity has been reported in many chronic diseases including cancer. Existing data suggest that fluctuations or reset homeostasis in normal growth factor production due to specific agents or changes in cellular environment are potential mechanisms of colonic carcinogenesis. Currently identified risk factors for colorectal cancer include diet, non-steroidal anti inflammatory drug use, alcohol consumption and physical activity. Certain constituents of diet, including retinoids, fish oils and soybeans, inhibit the activity of PDGF and could reduce paracrine stimulation of the colonic epithelium. Aspirin and physical activity, through reduction in platelet aggregation, may inhibit platelet release of PDGF and lead to reset homeostasis. Alcohol affects platelet aggregation and, depending on consumption patterns, could alter platelet release of PDGF. It is important to determine which of these environmental factors may result in transient effects on growth factor activity and which result in long-term adaptive responses. Further studies could examine the impact of these risk factors on (1) growth factor communication between colonic epithelial cells and fibroblasts in vitro and (2) PDGF concentrations and mitogenic activity in blood and tissue obtained in population-based studies of colorectal cancer. PMID- 8490538 TI - Screening for alimentary cancer: outstanding problems and a new strategy for research. PMID- 8490539 TI - Diet and cancer risk: an overview of Spanish studies. AB - Diet has been identified as a risk factor for various cancers. The geographic distribution of cancer frequency within the European Economic Community shows how the Mediterranean area has the lowest incidence rates for most tumours associated with diet. The first studies on diet and cancer realized in this area are fairly recent and their results have been especially informative. This article endeavours to review Spanish epidemiological studies on diet and cancer, highlighting the most important findings on colorectal, stomach, bladder and breast cancer and the repeated observations of the protective effect of high vegetable consumption of different tumours. PMID- 8490540 TI - Effectiveness of colorectal cancer screening: results from a population-based case-control evaluation in Saarland, Germany. AB - In order to evaluate the effectiveness of colorectal cancer screening by the faecal occult blood test (FOBT) in Germany a population-based case-control study was conducted in Saarland, a southwestern state of Germany. As cases, we identified 522 persons (244 males, 278 females) who died of colorectal cancer between 1983 and 1986 between the ages of 55 and 75 years. For 163 male cases complete screening histories were retrieved together with up to five age-matched controls who had not died of colorectal cancer identified from the files of the case's referring general practitioner (GP). For 209 female cases screening histories were retrieved from their GPs and gynaecologists as well as for age matched controls. Individual screening histories were established with emphasis on identifying whether FOBTs were carried out asymptomatically or symptomatically. In the time period 6-36 months prior to diagnosis 13% of the male cases and 14% of the male controls had at least one asymptomatic FOBT with a corresponding matched odds ratio of 0.92 (95% CI: 0.61, 1.75). For the same prediagnostic period 16% of the female cases and 29% of the female controls had at least one asymptomatic FOBT leading to an odds ratio of 0.43 (95% CI: 0.27, 0.68). Thus, for males where participation rates are generally low, no protective effect could be seen but for females where participation rates are higher a clear protective effect is seen. Possibilities for bias need to be taken into consideration when interpreting these results. Organizational measures ensuring a high penetrance of a mass screening programme are seen as a way to elevate efficacy. PMID- 8490541 TI - Involvement of general practitioners in mass screening. Experience of a colorectal cancer mass screening programme in the Calvados region (France). AB - Good compliance with screening programmes is essential and experience from ongoing studies points to the importance of involving general practitioners (GPs). The aim of this study was to evaluate factors influencing the participation of GPs in a screening programme, as well as acceptance of the test by the population. Fifty GPs were randomly chosen among the 117 practices of three districts in Calvados (France) where haemoccult test-based mass screening for colorectal cancer was underway. Each GP was asked to fill in a personal questionnaire as well as a detailed record for each patient between 45 and 74 years seen in the practice during a 1-week period. The GPs offered the test to 95% of the patients. The overall refusal rate was 7.8%, and was higher in women than in men (9.9% vs 5.9%; P < 0.05). Manual workers had a lower refusal rate than other occupational groups (2.5% vs 8.5%; P < 0.05). The GP's motivation was an important factor in patient compliance: the refusal rate was 5.4% in the case of highly motivated GPs, against 20.0% when the GP was poorly motivated (P < 0.01). GP motivation was higher in urban than in rural areas (P < 0.05) but did not depend on sex, age or the duration or type of practice. According to the GPs, motivating factors were the perceived need for screening, involvement in planning the campaign, and regular feedback. Conversely, a lack of time and the possibility of false-negative results were the most important impediments. This study demonstrates that patient compliance is closely linked to practitioner motivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490542 TI - A feasibility study on weight reduction in obese postmenopausal breast cancer patients. AB - An attempt was made to undertake a randomized clinical trial of weight reduction in obese postmenopausal breast cancer patients as an adjuvant to primary surgical and radiotherapeutic treatment. The rationale was to improve prognosis which has been shown to be worse in the obese (probably because of its effect on extra ovarian oestrogen production). Difficulties in recruiting a sufficient number of patients and the introduction of tamoxifen as anti-oestrogenic adjuvant therapy led to the decision to modify the aim of the study by limiting it to a feasibility study in 102 patients. In three hospitals in The Netherlands and in two hospitals in Poznan, Poland these patients were randomized in intervention and control groups according to a 3:2 ratio. Weight reduction in the intervention group was achieved by dietary means, ie caloric restriction was adapted to personal needs and behaviour of the patients. After 1 year a median weight loss of 6 kg was reached in both countries. In the Netherlands further follow-up indicated that this result could be maintained for another 2 years. PMID- 8490543 TI - Characteristics of the gastric mucosa of direct relatives of patients with sporadic gastric carcinoma. AB - We compared the gastric mucosa lesions of 63 direct relatives of 24 patients with gastric carcinoma with those observed in 151 dyspeptic patients and in seven members of a family with familial gastric carcinoma of diffuse type. We found a higher prevalence of Helicobacter pylori infection (96.8%) and gastritis (98.4%) in the relatives of patients with sporadic carcinoma than in the dyspeptic patients. One-third of the individuals of the former group displayed chronic atrophic gastritis and intestinal metaplasia. Dysplasia was only observed in the group of cancer patient relatives. The relatives of patients with intestinal carcinoma showed a higher prevalence of chronic atrophic gastritis (40.0%), incomplete intestinal metaplasia (22.9%) and dysplasia (5.7%) than the relatives of patients with diffuse carcinoma (10.0%, 0.0% and 0.0%, respectively). The only striking feature that emerged from the comparison of relatives of patients with sporadic gastric carcinoma with the members of the family with familial gastric carcinoma was the significantly higher prevalence of hyperplastic lesions (100%) in the latter group. These results reinforce the existence of two main pathways of carcinogenesis of gastric mucosa, one leading to intestinal carcinoma via chronic atrophic gastritis and intestinal metaplasia and the other leading to diffuse carcinoma via hyperplastic changes. PMID- 8490544 TI - Asbestos-related familial mesothelioma. AB - Familial mesotheliomas are reported in four pairs of patients. The group includes six men and two women, aged between 44 and 84 years. A blood relation (father son) existed in two pairs only. All the present patients had histories of exposure to asbestos; in five cases exposure had occurred in the shipyards. Familial mesothelioma could represent a useful model for investigating genetic environmental interactions. PMID- 8490545 TI - WHO initiative: cancer prevention in Europe. AB - In recent years, the countries of central and eastern Europe, the Baltic States, and the newly-independent countries (established in place of the former Soviet Union), have experienced a much heavier burden of cancer as compared to other subregions of Europe. This appears to be the result of a decline in the standard of health care services, environmental neglect and the high prevalence of health damaging behaviour, smoking in particular. Their anti-cancer potential falls short of their needs. The existing and still widening gap between what are considered best and worst patterns, practices and prospects in cancer control in Europe has posed a challenge to both the World Health Organization (WHO) and the international cancer community. On WHOs initiative, a group of major European cancer organizations is determined to use their considerable potential, both moral and scientific, in supporting national efforts in all possible ways in those countries that need progress. Recently, WHO has initiated an all-European alliance with the intention of narrowing the gap between what are regarded as best and worst patterns, practices and prospects in cancer control in Europe. PMID- 8490546 TI - Public information: a major tool in cancer prevention. AB - The methodology for an information campaign is discussed, detailing follow up in five stages: (1) assessment of needs: a good knowledge of behaviour patterns and the kind of information needed is the basic element to create the concept of a campaign. A pre-survey is an indispensable tool to secure this information; (2) basic scientific information: communication to the public has to be based on precise and recent scientific data; (3) comprehension of the information: communicating with the general public should be through texts that are clear and accessible to the greater part of the population; (4) production of supporting documents: each element of the campaign has to produce an impact on the person receiving the message; and (5) evaluating the impact of an information campaign. An evaluation can check whether objectives have been reached, and also correct errors and help prepare the next campaign even more professionally. These five stages are essential to set up a successful information campaign. We also give examples from our magazines Cancer-info and Smoke Buster-info. Through information public opinion can be mobilized to influence political decisions in the public health sector. One evidence for the importance of collective influence on political decision makers is our campaign to promote the total ban on tobacco advertising. As large-scale information campaigns need important financial resources it is essential to balance the cost to generate sufficient funds to finance further projects in the health sector; we discuss this matter as well as the impact on the image of the association.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490547 TI - Colon cancer prevention: role of the endoscopy. Review of the new histopathological techniques. PMID- 8490548 TI - Gastric screening prospects. AB - The incidence of gastric cancer is rapidly declining in the Western world, but it remains high in the Third World and in Japan. Systematic screening for gastric cancer has been undertaken in Japan, where barium X-ray is used in people over the age of 40. Evaluation data suggest a benefit in reduced mortality, but biases cannot be ruled out. A similar screening programme has been started in Venezuela. Currently, stomach cancer screening programmes cannot be recommended as public health policy, except in high-risk areas where they have already started. The Correa model of gastric carcinogenesis states that environmental influences cause a normal gastric mucosa to undergo successive stepwise changes, through superficial gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, carcinoma and, finally, invasion. Incriminated environmental influences include irritant, antibodies, gastrectomy, nutritional deficits, intake of nitrogen compounds and Helicobacter pylori. These bacteria cause a chronic superficial gastritis, which may develop into atrophic gastritis. H. pylori is less frequently found in advancing preneoplastic lesions, and seldomly in gastric carcinoma tissue (it may, however, be identified more readily in the surrounding non-cancerous tissue). Several lines of evidence suggest that H. pylori may play an important role in human gastric carcinogenesis. We found that in some patients with H. pylori infection and without preneoplastic lesions, the gastric cell turnover was increased; this was correlated with the intensity of the inflammatory changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490549 TI - Breast cancer screening programmes--results of studies in foreign countries- situation in Belgium. AB - Results of randomized trials and case-control studies on breast cancer screening are reviewed. A combined analysis of data from the randomized studies indicates that a mortality reduction (29%) can be achieved by mammographic screening in women. Regular breast cancer screening by mammography for women aged 50-69 years reduces breast cancer mortality by 40% (confidence interval [CI] 95% about 27-55) in women who are screened at least once. In younger women, the results are inconclusive. The programme Europe against Cancer has recommended the setting-up of a network of pilot studies on breast cancer screening by mammography in the European Community in order to obtain the necessary experience, with a view to implementation of a national screening programme before the year 2000. In the Brussels project, the main objective is to develop a programme of quality assurance. In Belgium, there are other projects with different designs, for which the results are not yet available. PMID- 8490550 TI - Computer modelling in predicting carcinogenicity. AB - The cytochrome P450-dependent mixed-function oxidases are the most important enzyme system in the oxidation of chemicals to their reactive intermediates which then interact with cellular components to provoke toxicity and carcinogenicity. These enzymes comprise a multifamily of proteins, two families of which, namely CYP1A and CYP2E, activate planar and small molecular weight compounds, respectively. A computer graphic procedure (COMPACT) has been developed which, based on the molecular shape and electronic structure of the chemical, determines whether the chemical will interact with these two particular cytochrome P450 families and thus be metabolized to toxic and carcinogenic intermediates. As the basal levels of these enzyme families are low, the ability of the chemical to induce them selectively, on repeated administration, is an important determinant of its carcinogenic potential. Inductive capability may be determined in short term experiments (ENACT) utilizing a small number of animals. Thus the combination of COMPACT and ENACT provides a rapid and inexpensive means for the preliminary screening of chemicals, before the long term and expensive rodent lifetime bioassays are undertaken. PMID- 8490552 TI - Sounding a certain trumpet: case management as a catalyst for the empowerment of people with developmental disabilities. AB - The Developmental Disabilities Assistance Act of 1987 (P.L. 100-146) conceptualized case management as a process by which to "increase and support the independence, productivity and integration into the community of people with disabilities." There is a call from people experiencing disabilities to meet this mandate by a process of empowerment, enabling them to assume control of and responsibility for issues impacting their daily life. This article examines current outcomes and expectancies pertaining to integration, independence and productivity and suggests an orientation within which individual empowerment and self-determination, and consequently independence, and integration, are central outcomes. PMID- 8490551 TI - Preventive measures against breast cancer: but when? PMID- 8490553 TI - Approaches to case management in Puerto Rican communities. AB - This article reviews some critical elements of case management as they apply to Puerto Ricans seeking quality and consistency in health care and social services in a system which is culturally foreign, difficult to negotiate, and frequently unresponsive, especially to those with limited economic resources and government rather than private insurance. Following a brief outline of some principles of case management, we discuss aspects of Puerto Rican history, family organization, and health-seeking behavior that relate to case management. Descriptions of three programs illustrate several case management approaches that combine methods to access care with those needed to organize coordinated inter-institutional care. Finally, we suggest ways for case managers to successfully work with Puerto Rican families. PMID- 8490554 TI - Alzheimer's disease: case management in a rural setting. AB - This article describes a case management model developed under the guidelines of the Medicare Alzheimer's Disease Demonstration. This delivery model currently provides services to over 400 Alzheimer's disease victims and their family caregivers who reside in predominantly rural communities in east central Illinois and western Indiana. Client and caregiver characteristics are provided as well as service utilization patterns. The model incorporates intervention strategies that facilitate communication and coordination of services, integrates formal and informal support systems, and allows for client advocacy and system development. PMID- 8490555 TI - Case management for persons who are homeless. AB - Comprehensive, client-centered continuous care with a multidisciplinary team using the case management model has proven to be essential in providing health care services to the homeless. Despite their heterogeneity, homeless persons share the common experiences of being poor, isolated, and in crisis. The process of case management is inherently therapeutic for its recipients and providers. It has the potential to be a source of human support for those who have none. Case management models can be effective systems for providing health care to these persons while addressing their special needs and characteristics. PMID- 8490556 TI - Aging and ethnic identity: a refutation of the double-jeopardy theory. AB - Ethnic identity has been commonly stereotyped in the gerontological literature as a disability for the elderly, placing them in so-called double jeopardy. However, new knowledge and changing attitudes in American society have resulted in a far more positive attitude toward the role of cultural pluralism. Ethnographic field research strongly suggests that ethnic affiliation can proffer the elderly a spectrum of psychological, social, and cultural resources not generally available to them in the larger society. For case managers with largely ethnic client populations, understanding the dynamics of ethnicity can enhance their ability to meet client needs successfully with resources from both within and outside the client's culture. PMID- 8490557 TI - Tumor necrosis factor-alpha is a direct hepatocyte mitogen in the rat. AB - We previously reported that tumor necrosis factor-alpha (TNF-alpha) increases in vivo hepatocyte mitoses and liver regeneration in rats. In the present studies, we used in vitro hepatocyte cultures to determine whether TNF-alpha itself was mitogenic or whether other cytokines (IL-1 beta and IL-6) that share similar actions with TNF-alpha might be involved. Hepatocytes were cultured with TNF alpha (4, 40 or 400 U/ml), IL-1 beta (0.1, 1 and 10 ng/ml) or IL-6 (0.2, 2, or 20 ng/ml) for 24 h and 3 d. Incorporation of [3H]thymidine was increased significantly by TNF-alpha (40 and 400 U/ml) at 3 d. Both IL-1 beta and IL-6 at all concentrations significantly decreased [3H]thymidine incorporation at 3 d. These results indicate that TNF-alpha has a direct mitogenic action on hepatocytes. In contrast, IL-1 beta and IL-6 appear to suppress DNA synthesis in hepatocytes. PMID- 8490558 TI - Peculiarities of the binding of restriction endonuclease EcoRII to synthetic DNA duplexes. AB - The binding of restriction endonuclease EcoRII to synthetic oligodeoxyribonucleotide substrates 11 to 30 bp long was investigated by gradient polyacrylamide gel electrophoresis under nondenaturing conditions in the absence of Mg2+ ions. Irrespective of the substrate's length, two types of specific DNA protein complexes were shown to be formed. Their mobility in gel was close to that of the monomer and the dimer of the marker ovalbumin. The number of such complexes in solution depended on the ratio of the molar concentrations of restriction endonuclease EcoRII and the DNA duplex. The possible structure of the complexes is discussed. PMID- 8490559 TI - Effect of polyamines on mitochondrial F-ATPase from Crithidia fasciculata and Trypanosoma cruzi. AB - ATP hydrolysis by Crithidia fasciculata mitochondrial ATPase was studied through the use of submitochondrial particles and the soluble enzyme. (a) ATP hydrolysis by these preparations was inhibited by spermine but not by spermidine or putrescine. (b) The ATPase activity inhibited by spermine was partially recovered when excess Mg2+ was added to the reaction mixture. (c) When polyamines were present throughout the preparation of the mitochondrial membranes, the membrane bound ATPase was irreversibly inactivated. The polyamine effect decreased in the order spermine > putrescine > spermidine. (d) The spermidine or putrescine pre treated membranes oxidized succinate at a faster rate than the control ones. (e) Trypanosoma cruzi F-ATPase was inhibited by polyamines in the same manner as the C. fasciculata enzyme. PMID- 8490560 TI - Immunization of rabbits with proteins reacted with malonic dialdehyde (MDA): kinetics and specificity of the immune response. AB - MDA-modified casein, lysozyme or polylysine (MC, ML and MP respectively), was intradermically injected to rabbits in the presence of complete Freund's adjuvant (cFA). Two other animal sets received either cFA alone, or MDA alone. MDA, cFA and MP did not induce any antibody response. Both ML and MC produced an increase of antibody reactivity towards ML, but reactivity towards native lysozyme (L) was increased only by ML and not by MC. According to these results, it was concluded that the epitopes recognized by antibodies reacting with ML and not with L are AIP bridges and possibly the two surrounding aminoacyl (especially lysyl) residues. PMID- 8490561 TI - Comparative study of the properties of plasmid mediated staphylococcal beta lactamase as expressed in Escherichia coli. AB - An unmodified natural plasmid of Staphylococcal origin having beta-lactamase determinant was introduced by transformation into Gram-negative Escherichia coli HB101 recA-SmR (plasmidless). Beta-lactamase of Staphylococcus aureus is extracellular. In recipient transformed E. coli HB101, the enzyme shows periplasmic location. The enzyme is expressed well in E. coli, and the basal level of enzyme production in E. coli, is approximately 3-4 fold higher than that of S. aureus. Beta-lactamase is inducible both in S. aureus and E. coli. Enzymatic properties as indicated by substrate profile and Km values are found to be similar. PMID- 8490562 TI - Differential regulation of glucokinase and GLUT-2 glucose transporter gene expression in pancreas and liver from neonatal and 16 day old rats. AB - Glucokinase and GLUT-2 high Km glucose transporter gene expression were studied in pancreas and liver from 2 day old neonatal and 16 day old rats. In pancreas tissue the glucokinase gene was transcribed into a 2.8 kb and a 4.4 kb mRNA species. However, while the 2.8 kb transcript was expressed already in pancreas from 2 day old neonatal rats, distinct expression of the 4.4 kb transcript occurred only in the pancreas from 16 day old rats. GLUT-2 glucose transporter was expressed already in the pancreas from 2 day old neonatal rats, albeit to a lesser extent than in the pancreas from 16 day old rats. Liver glucokinase gene was not expressed in 2 day old neonatal rats but in 16 day old neonatal rats, whereas the GLUT-2 glucose transporter gene was expressed both in the liver from 2 day old neonatal and 16 day old rats. The differences between glucokinase gene expression in neonatal pancreas and neonatal liver provide an indication for a different function of this enzyme in the two tissues. The immature insulin secretory response to glucose in neonatal pancreas may be related to a deficient glucokinase and probably also to a reduced GLUT-2 glucose transporter gene expression. PMID- 8490563 TI - Influence of antioxidant vitamins on fatty acid inhibition of lymphocyte proliferation. AB - Fatty acids, especially polyunsaturated fatty acids (PUFAs), inhibit a number of lymphocyte functions, including proliferation, cytokine production and cytotoxicity, but their mechanism of action is not known. This study investigated whether fatty acids inhibit lymphocyte proliferation by leading to the production of lipid peroxides, which are known to inhibit the growth of cells. The so-called "thiobarbituric acid-reactive substances" (TBARS) and lipid hydroperoxide contents of lymphocytes (0.75 +/- 0.04 and 1.30 +/- 0.39 nmol/mg protein in fresh cells, respectively) were increased by 48 h culture to 0.96 +/- 0.14 and 3.23 +/- 0.47 nmol/mg protein, respectively. The TBARS content was increased by culture in the presence of 100 microM PUFAs to between 1.46 +/- 0.11 (linoleic acid) and 2.39 +/- 0.31 (docosahexaenoic acid) nmol/mg protein. The lipid hydroperoxide content was increased by culture in the presence of 100 microM PUFAs to between 11.65 +/- 1.12 (linoleic acid) and 22.24 +/- 1.26 (docosahexaenoic acid) nmol/mg protein. These increases were partially prevented by inclusion of 10 microM vitamin E in the culture medium. Vitamin E (1 or 10 microM) enhanced concanavalin A-stimulated rat lymphocyte proliferation by approximately 45%. Vitamin E (10 microM) increased human lymphocyte proliferation by 35%. However, vitamin E did not prevent the inhibitory effects of fatty acids upon lymphocyte proliferation. It is concluded that inhibition of lymphocyte proliferation by fatty acids is not caused by their conversion to peroxidised products. PMID- 8490564 TI - Purification and some properties of peroxidase isozymes from pineapple stem. AB - The enzyme peroxidase is widely distributed among the higher plants. Isozymes of peroxidase are known to occur in a variety of tissues in a large number of plant species. In this study, peroxidase isozymes were purified from the extract of pineapple stem through successive steps of ammonium sulfate fractionation, CM Sepharose CL-6B chromatographies and DEAE-Sepharose CL-6B chromatographies. By these steps, twelve isozymes of peroxidase were obtained. Some properties of the isozymes were studied and compared. PMID- 8490565 TI - A small novel chloroplast ribosomal protein (S31) that has no apparent counterpart in the E. coli ribosome. AB - Higher plant chloroplast ribosomes contain several novel protein components whose homologues are not present in the eubacterial E. coli ribosome, indicating a complex evolution of the chloroplast translational apparatus following the endosymbiotic event. Here we describe the isolation and characterization of a new small protein from spinach chloroplast ribosome which has, based on the amino acid sequence and immunological data, no counterpart in the E. coli ribosome. We suggest a nomenclature suitable for this protein and other novel proteins in the chloroplast ribosome. PMID- 8490566 TI - Effects of various dietary fatty acids on enzyme activities of carbohydrate and glutamine metabolism and the metabolic response of lymphocytes and macrophages during Walker-256 ascites cell tumour growth in rats. AB - It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity. PMID- 8490567 TI - Nonradioactive assay for adenosine 5'-phosphosulfate sulfotransferase using reversed-phase ion-pair high-performance liquid chromatography. AB - A nonradioactive and simple method for the assay of adenosine 5'-phosphosulfate sulfotransferase (APSSTase) is described. The method is based upon the quantitative measurement of the substrate adenosine 5'-phosphosulfate and/or product AMP by ion-pair reversed-phase high-performance liquid chromatography on a C18 column. Isocratic elution renders the method simple and fast. This method is standardized for partially purified APSSTase from the marine red macroalga Porphyra yezoensis. PMID- 8490568 TI - Retinoblastoma gene inhibits transactivation of HIV-LTR linked gene expression upon co-transfection in He La cells. AB - Co-transfection of HeLa cells with plasmids carrying human immunodeficiency virus (HIV) control elements along with plasmids harboring human retinoblastoma (RB) gene, results in the repression of transactivation of genes linked to HIV elements. Cells transfected with HIV LTR-linked chloramphenicol acetyl transferase (CAT) and TAT genes showed a dose-dependent decrease in CAT activity when increasing amounts of RB genes were transfected along with HIV genes. CAT mRNAs were not detected in HeLa cells transfected with HIV LTR CAT gene alone. Upon cotransfection of these cells with pTAT gene, large quantities of CAT messengers were observed. The TAT gene mediated expression of CAT gene was inhibited when cells were co-transfected with RB gene. These studies suggest that the RB gene represses HIV LTR directed CAT gene expression by interfering with the expression of HIV TAT gene. PMID- 8490569 TI - Effects of guanidine hydrochloride on catalytic efficiency of glycine amidinotransferase of rat. AB - Guanidine-induced alterations in substrate-dependent kinetics of glycine amidinotransferase (GAT) have been investigated in homogenates of rat kidney. Guanidine hydrochloride (GuHCl) induced a mixed type of inhibition by decreasing the maximal velocity (Vmax) and increasing the Michaelis-Menten constant (Km). The finding of a value of Ki smaller than that of Ki' denoted that the inhibition of GAT may be due to decreased E to S affinity rather than to reduction in the active site density of the enzyme. PMID- 8490570 TI - Comparative analyses of IgA1 binding lectins from seeds of six distinct clones of Artocarpus integer. AB - Purified lectins from seeds of six distinct clones of Artocarpus integer (lectin C) were shown to be structurally and functionally similar. All lectins comprised of two types of non-covalently-linked subunits with apparent M(r) of 13,300 and 16,000. The lectins appeared to interact with several human serum proteins, with the predominance of the IgA1 and C1 inhibitor molecules. Interaction was not detected with IgA2, IgD, IgG and IgM. The lectin Cs were also shown to precipitate monkey, sheep, rabbit, cat, hamster, rat and guinea-pig serum. Due to their uniform properties, lectin C may provide better alternative to the Artocarpus heterophyllus lectin, jacalin, for use in future investigations. PMID- 8490571 TI - In vitro effect of testosterone propionate on lactate dehydrogenase and malate dehydrogenase in brain and gonads of Channa punctatus. AB - The activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and protein levels were measured in vitro incubation of tissue homogenate of brain and gonads with testosterone propionate (TP) in Channa punctatus (teleost). The activities of LDH and MDH were found to be highest in the ovarian tissues in comparison to the testis and the brain in control fish. TP (2 micrograms-4 micrograms/ml) stimulated testicular tissue with increases in LDH by 10-fold and MDH by 15-fold approximately, the ovary with significant increase in LDH and a decrease in MDH and the brain showed only an increase in MDH. PMID- 8490572 TI - Properties of Azotobacter vinelandii rhodanese. AB - Rhodanese (thiosulfate: cyanide sulfurtransferase, E.C. 2.8.1.1) was purified from the nitrogen fixing organism Azotobacter vinelandii, and its amino acid composition was determined. The enzyme is a single polypeptide chain of M(r) 29,000 which showed an apparent pI of 4.7 and no presence of isoenzymes. Steady state initial velocity measurements indicate that the enzyme catalyzes the transfer of sulfane sulfur of thiosulfate either to cyanide or to dihydrolipoate by way of a double displacement mechanism. PMID- 8490573 TI - Intrinsic crotonase activity in a bacterial butyryl-CoA dehydrogenase. AB - Butyryl-CoA, crotonyl-CoA or 3-hydroxybutyryl-CoA all ultimately form an enzyme acetoacetyl-CoA complex upon aerobic addition to butyryl-CoA dehydrogenase purified from Megasphaera elsdenii, implying the presence of crotonase activity. This behaviour remains even after treatment with 6M urea, which destroys the activity of the main crotonase fraction from M. elsdenii. Flavin-sensitised photoinactivation destroys residual crotonase and dehydrogenase activities in parallel. Butyryl-CoA dehydrogenase thus has intrinsic crotonase activity with a turnover rate (0.05 min-1) about 0.02% of the figure for dehydrogenase activity. Mechanistic implications are discussed. PMID- 8490574 TI - Distribution of [241Am] in hepato-pancreatic nuclear proteins of the lobster (Homarus gammarus). AB - Recent studies on the bio-accumulation of transuranic elements in marine invertebrates have demonstrated an intracellular concentration of radionuclides in the digestive gland. The present investigation aims to establish the distribution of [241Am] within the different structures of the cell nucleus. Lobsters were experimentally contaminated through feeding and then killed. The nuclei of hepato-pancreatic cells were isolated, purified and dissociated. The different protein categories were separated in media of increasing ionic strength. The distribution of americium in this material yielded results showing a preferential fixation onto the structural proteins of the nuclear matrix. The radiological consequences of such an affinity are discussed in terms of the life times of the ligands concerned. PMID- 8490575 TI - Ca(2+)- and Mg(2+)-dependent binding of annexin II and its complex to phospholipid vesicles; a comparative spectroscopic study. AB - The binding of annexin II (p36) and of its complex ((p36)2 (p11)2) to model phospholipid vesicles led to conformational changes of the proteins which were studied by fluorescence spectroscopy. Titrations with liposomes of different kinds showed that the presence of the p11 dimer in the complex enhances the conformational change of the annexin II. Comparative liposome titrations were carried out in the presence of Mg2+: the binding of the protein to liposome induced a much smaller protein conformational change in this case. Moreover, Ca2+ and phospholipid binding order experiments showed that the protein conformational change only occurred when both are bound. PMID- 8490576 TI - Electrophoretic analysis of endotoxin-activated gelation reaction of Carcinoscorpius rotundicauda amoebocyte lysate. AB - Electrophoretic analysis of a 60 min reaction between E. coli endotoxin and the amoebocyte lysate showed that the coagulation reaction was complete by 15 min, with the conversion of coagulogen (21 kDa) to coagulin (17 kDa). Coincident with this observation was the maximal activities at 15 min, of Factor C and proclotting enzyme. On agitation of the coagulin gel clots, bioactive endotoxin was recovered. Densitometric scan of the electrophoretically-resolved proteins showed that the sum of coagulogen and coagulin remained almost constant at various time intervals of the coagulation reaction. Electrophoresis serves as a convincing and visually discernible method of studying the kinetics of coagulation, and defining the onset and completion of gelation. Furthermore, it is a useful means of examining the integrity of fresh lysate preparations based on the presence or absence of the 17 kDa coagulin band. PMID- 8490577 TI - Presence of growth hormone receptors in carp liver and intestine. AB - Membranes were prepared from tissues of the carp Ctenopharynogodon idellus including liver, kidney, intestine, adipose tissue, ovary, gill, heart, muscle and spleen. The carp liver and intestine membranes bound 125I-labeled bovine growth hormone and the binding could be displaced by cold bovine growth hormone. No changes in the ability to bind 125I-labeled bovine growth hormone occurred after treatment of the carp liver membrane with DNase, RNase, alpha-amylase and beta-glucosidase, suggesting that neither nucleic acids nor carbohydrates played an important part in the hepatic binding of growth hormone. Treatment of carp liver membranes with either chymotrypsin or trypsin produced a decrease in the growth hormone binding activity, indicating that the growth hormone receptor on carp liver membrane is a protein. Treatment of carp liver membranes with p chloromercuribenzoate brought about a reduction in 125I-bGH binding. The inhibition could be reversed by dithioerythritol, suggesting the involvement of essential sulfhydryl group in bGH binding. PMID- 8490578 TI - Nontarget effects of carbaryl and its hydrolysis product, 1-naphthol, towards Anabaena torulosa. AB - The toxic effects of carbaryl and its hydrolysis product, 1-naphthol, singly and in combination, towards a filamentous diazotrophic cyanobacterium, Anabaena torulosa, were determined. The toxicity criteria employed, viz., packed cell volume, chlorophyll a, phycocyanin, carotenoids, heterocyst differentiation and nitrogen fixation, were greatly affected by the toxicants above 25 micrograms/ml concentrations. However, 1-naphthol was more toxic to the diazotroph than was carbaryl. The toxicity was more pronounced when carbaryl and 1-naphthol were in combinations even at lower concentrations. PMID- 8490579 TI - The effect of cations on the thermophilic character of alkaline phosphatase from Thermoactinomyces vulgaris. AB - The effect of cations on the thermophilic character of alkaline phosphatase from Thermoactinomyces vulgaris, is described. The optimal pH and temperature were 9.5 and 55 degrees C to 65 degrees C, respectively. The partial removal of cations with ethylene diamine tetraacetic acid converted the enzyme to mesophilic and susceptible to chemical denaturation. Their complete removal caused complete inhibition. The addition of 0.3mM cobalt and 10mM magnesium added before heating were found to be optimal for restoring its thermophilic character and its stability to a chemical denaturant. PMID- 8490580 TI - Identification of a novel aspartyl endothelin converting enzyme in porcine aortic endothelial cells. AB - An enzyme which catalyzes the conversion of proendothelin-1 to the potent vasoconstrictor peptide endothelin-1 has been identified in the detergent extract of primary porcine aortic endothelial cell membranes. Partial purification was accomplished by anion exchange and Con A affinity chromatography. The enzyme was active at pH 4 and was inhibited by 100 nM peptstatin A. Hydrolysis products of proendothelin-1 were characterized by bioassay, RIA, HPLC and molecular mass analysis. Comparisons to cathepsin D and renin demonstrated that the endothelin converting enzyme activity from the porcine aortic endothelial cells was unrelated to the known enzymes. These results suggest that the processing of proendothelin-1 by endothelial cells involves a novel pepstatin-sensitive aspartyl protease. PMID- 8490581 TI - Effect of magnetic fields on membrane associated enzymes in chicken embryos, permanent or transient? AB - Exposure to a 60Hz, 4 microT electromagnetic field resulted in a significant reduction in the activity level of 5' nucleotidase in normal live embryos. Levels of acetylcholinesterase and alkaline phosphatase were not affected. The effect of the field on 5'NT levels appears to be permanent, as incubation in a field free environment for a further 15 days did not result in enzyme levels returning to control values. PMID- 8490582 TI - Serial quantitation of hyaluronan and sulfated glycosaminoglycans in fetal sheep skin. AB - Fetal wounds are abundant in hyaluronic acid (HA), but little is known as to the total HA content of fetal tissues as a function of gestational age. Previous studies demonstrated scarless healing prior to approximately 130 days gestation, after which disorganized collagen deposition became prevalent. Glycosaminoglycans (GAGs) have been shown to play an important role in wound healing, cytodifferentiation, and morphogenesis. In this study, we examined the HA and GAG content of fetal sheep skin of increasing gestational age. We found that the total amount of HA and GAGs declined from a high at 80 days gestation (528 +/- 9 micrograms/gm) to a low at 130 days (174 +/- 11). Analysis of the various GAG species revealed that HA comprised the largest fraction (75-96%). The sulfated GAGs, Heparan Sulfate (HS) and Dermatan Sulfate (DS), were not present in the extracellular matrix until 120 days gestation. Both the trough of HA content and the appearance of sulfated GAGs in the extracellular fraction correspond to the appearance of scarring in fetal sheep wound repair. PMID- 8490583 TI - Oxidation of aniline to nitrobenzene by nonheme bromoperoxidase. AB - Nonheme bromoperoxidase found in Pseudomonas putida catalyzed the bromination of aniline with hydrogen peroxide and bromide ions to give o- and p-bromoanilines. However, in the absence of bromide ions, it oxidized aniline via azobenzene and azoxybenzene finally into nitrobenzene. This is the first report of the biological oxidation of an arylamine to the corresponding nitrocompound at the enzyme level. In addition, nitrobenzene was not formed by a nonheme bromoperoxidase from Corallina pilulifera (marine alga), implying that the alga enzyme has a different reaction mechanism. PMID- 8490584 TI - Quality of life. 1. Perspectives. AB - Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring quality of life has become more frequent. Methodologies have also developed rapidly. At the same time, methodological problems continue to be troubling. In part, this explains the relative lack of use of validated measures of quality of life in clinical trials. In the future, measuring quality of life will certainly become more frequent. It may even be demanded by policy making bodies. Increasingly, too, economic costs will be part of such studies. This requires considering both clinical and economic data. PMID- 8490585 TI - Quality of life. 2. Economic analysis of drug therapies. AB - In 1990, health care expenditures in the United States reached $666.2 billion, 12.2% of the gross domestic product (GDP). It is projected for the year 2000, the USA will spend $1.6 trillion for health care which will be comparable to 16.4% of that year's GDP. As a result of the rapid increase in costs of health care and limited resources available, patients, third-party payers and the government have initiated and implemented more rigid cost control measures. Economic analyses can help ensure the efficient use of health care dollars in areas such as drug therapy. The four methodologies available are cost-benefit analysis, cost effectiveness analysis, cost-minimization analysis and cost-utility analysis. This article reviews methods and provides examples from the medical literature. These tools can assist care providers in determining which treatments are most cost-effective. PMID- 8490586 TI - Utilization patterns of total parenteral nutrition in a university hospital. A methodological approach. AB - To study the utilization of total parenteral nutrition, using methodology recommended by the World Health Organization, classification of components in accordance with the anatomical therapeutic chemical classification and defined daily dose system is necessary. Anatomical therapeutic chemical indices are available but defined daily dose values have not been established yet. In this article, a methodology to study both the total utilization of total parenteral nutrition, the utilization of individual substances and the composition of total parenteral nutrition is presented. To validate the proposed methodology, the utilization of total parenteral nutrition in a teaching hospital is studied, based on pharmacy computer data. The total utilization of total parenteral nutrition in the hospital in 1990 is 1.4 defined daily doses/100 bed-days. The composition of total parenteral nutrition varied greatly between the clusters. In this study we showed that utilization of total parenteral nutrition can be measured with the proposed methodology, using a defined daily dose for total parenteral nutrition in concurrence with a defined daily dose for the individual components. PMID- 8490587 TI - Drug-utilization study on Curacao. AB - The drug use on Curacao was evaluated with the help of the prescription forms of twelve community pharmacies at Curacao over a period of three months. The emphasis of the study was on three therapeutic groups: the systemic antibiotics, the psycholeptics and the anti-inflammatory and antirheumatic drugs. Within the group of systemic antibiotics broad-spectrum antibiotics were very frequently prescribed compared with the small-spectrum penicillins. The consumption of psycholeptics, particularly benzodiazepines, on Curacao is remarkably low in comparison with drug utilization data of Denmark and the Netherlands. In contrast, the number of defined daily doses per 1,000 persons per day of antirheumatic drugs is higher compared with data from these two countries. Within the analysed groups, large differences occur between the two most important kinds of insurance, i.c., the poor people (PP) and social insurance bank (SVB) insurance. The PP-insured patients consume in the case of antibiotics and antirheumatic drugs almost twice as many and in the case of psycholeptics even five times as many as the SVB-insured patients do. A few calculations of prices prove that the extra amount of drugs consumed by PP-insured has important financial consequences. PMID- 8490588 TI - Pharmacokinetics and clinical study of cefotetan in bile: prophylactic use in biliary tract surgery. AB - The excretion of cefotetan, a 7 alpha-methoxy-cephalosporin, was studied in 27 patients undergoing biliary surgery. Pharmacokinetic parameters were determined after a single intravenous bolus dose of 1 g (10 patients) or 2 g (17 patients). Rapidly excreted in bile, cefotetan concentrations were considerably higher in bile [range: 92-2,594 mg.l-1 (1 g); 35-4,610 mg.l-1 (2 g)] than in plasma despite the presence of gall stones. Bile bactericidal activities against Staphylococcus aureus (MIC 8 mg.l-1) and Bacteroides fragilis (MIC 2 mg.l-1) correlated well with gall bladder cefotetan levels [r = 0.888 (1 g); r = 0.971 (2 g)]. No cefotetan was detected in the bile of 3 patients with nonfunctioning gall bladders. One other patient with very low activity and these three aside, the inhibitory quotients (cefotetan concentration/MIC) were > 4 for both doses against both bacteria. PMID- 8490589 TI - Diminished sedation during diazepam treatment for chloroquine intoxication. AB - We report a case of a woman hospitalized after chloroquine overdose whose whole blood concentration on admission was 7.87 micrograms/ml. High blood concentrations of chloroquine induce cardiotoxicity and have been associated with death when they exceed 3.0 micrograms/ml. Early administration of massive doses of diazepam has been described to reduce the mortality due to chloroquine toxicity, but the protective mechanism has remained unknown. This patient was treated with diazepam (2.0 mg/kg over 30 min followed by a dosage of 1.0 to 2.0 mg/kg over 24 h), yet she remained awake despite the high plasma concentrations of diazepam and nordiazepam which would normally be associated with sedation. This suggests an antagonistic effect of chloroquine on the benzodiazepine-induced sedation due to an interaction between these drugs at their site of action. PMID- 8490590 TI - Computational chemistry in biotransformational and toxicological research. Mechanisms of oxidation by and active site structure of cytochromes P-450. PMID- 8490591 TI - Aspects of medical therapy of neuroendocrine disorders. PMID- 8490592 TI - Intracellular cation concentrations in essential hypertension and chronic renal failure. AB - The aim of this study was to test basal and after treatment erythrocyte sodium and calcium concentrations, and calcium-ATPase activity and platelet cytosolic free calcium and pH in 20 normotensive controls, 20 hemodialysis-dependent chronic renal failure patients and in 18 essential hypertensives. Prior to treatment, essential hypertensive and uremic patients presented similar higher platelet calcium concentrations and lower pH than the normotensive control group. The erythrocyte sodium, calcium, and magnesium concentrations were only significantly elevated in chronic renal failure, with a significant decrease in the calcium-ATPase activity in the latter population. Hemodialysis partially reversed these intracellular ionic abnormalities with normalization of platelet pH. Significant correlations have been noted between weight loss and decreases in platelet calcium concentration (r = 0.60, p < 0.01) or in erythrocyte sodium (r = 0.50, p < 0.05). The systolic blood pressure decrease was only correlated to the increase in calcium-ATPase activity (r = 0.57, p < 0.05). Antihypertensive treatment (captopril and nifedipine) only tended to normalize the intracellular calcium concentration with correlation between the decrease of the latter and blood pressure decrease (r = 0.64 for the systolic blood pressure and 0.68 for the diastolic blood pressure, p < 0.01). Thus, in essential hypertension and in uremia, some cellular ionic abnormalities exist in platelets in baseline condition. Moreover, in uremia, erythrocyte presents abnormal ionic pattern. Some, but not all of these abnormalities could be corrected by treatment affecting blood pressure (cellular calcium) in essential hypertension or by hemodialysis (cellular sodium, calcium, and pH). In the latter treatment, the changes are linked to extracellular fluid modification. In essential hypertension, the intracellular calcium reduction was linked to blood pressure decrease. PMID- 8490593 TI - Hypertension decreases small arteriole responses to acetylcholine in skeletal muscle. AB - Television microscopy was used to quantitate in vivo the responses of skeletal muscle small arterioles to acetylcholine. Five groups of rats were used: normotensive and one (1K1C)- and two (2K1C)- kidney one clip renovascular hypertensive Sprague-Dawley rats (SDR), as well as WKY normotensive and spontaneously hypertensive (SHR) rats. Third-order arterioles dilated to acetylcholine with an EC50 of 3 x 10(-7) M in SDR and 10(-6) M in WKY animals. In contrast, the concentration-response curve to acetylcholine was shifted to the right (less reactive) by 100 fold in the 1K1C- and by 1000 fold in the 2K1C hypertensives. The dose-responsive curve to acetylcholine was shifted 10-fold to the right in the SHR's compared to the WKY's. Because acetylcholine acts through endothelium-dependent mechanisms and because maximal vasodilation could be induced by an endothelium-independent vasodilator, Na-nitroprusside, in all but the 2K1C-group, we conclude that different forms of hypertension interfere to a variable degree with endothelium-dependent vasodilator mechanisms in the skeletal muscle microcirculation. PMID- 8490594 TI - Decreased arteriolar endothelium-derived relaxing factor production during the development of genetic hypertension. AB - In the present study, basal and stimulated production of endothelium-derived relaxing factor (EDRF) were examined in young (4-5 week-old) and mature (10-12 week-old) spontaneously hypertensive rats (SHR) and were compared with those of age-matched Wistar Kyoto (WKY) normotensive rats. Nw-nitro-L-arginine methyl ester (L-NAME) was used as a probe for basal EDRF production in vivo. We also determined the dose-response effects of acetylcholine (Ach, 10(-9)-10(-5) M), sodium nitroprusside (NP, 10(-9)-10(-5) M), and norepinephrine (NE, 3 x 10(-10) 10(-6) M), on third-order arterioles (3A) in the two age groups. Relaxation of 3A vessels in response to Ach was significantly lower (p < 0.01) in mature SHR than in WKY rats. No significant differences were observed in responses to Ach in young animals or in responses to NP in either age groups. Preincubation with L NAME (2 x 10(-4) M) shifted the dose-response curves of NE to the left in mature WKY rats (n = 6), but not in mature SHR (n = 6). These data indicate that both basal and stimulated production of EDRF are decreased in small arterioles in the striated muscle microcirculation at an established stage of genetic hypertension. These data suggest that a diminished EDRF response by arterioles may be in part responsible for the elevated microvascular reactivity observed in genetic hypertension. PMID- 8490595 TI - Pressor hormone profile during stress in hypertension: does vasopressin interfere with left ventricular hypertrophy? AB - Neurohormonal factors may account for the fact that patients with similar severity and duration of hypertension develop different degrees of left ventricular hypertrophy (LVH). The purpose of this work was to compare the pressor hormone profiles of hypertensive subjects off medication during exercise testing. Nineteen patients, stratified according to echocardiographically diagnosed absence (Group I n = 6) or presence (Group II n = 13) of LVH, underwent testing on the treadmill according to the Bruce protocol. Both groups were comparable in age, severity and duration of hypertension and reached similar double product at peak exercise. Measurements of plasma renin activity (PRA), plasma catecholamines and vasopressin (AVP) at baseline, peak exercise and post exercise revealed significant differences between groups: Group I had suppressed PRA levels throughout and had significantly higher baseline AVP levels, which increased further at peak effort. Group II had significantly higher baseline PRA levels, which tended to increase further at peak effort, and had suppressed AVP levels throughout. There was a significant negative correlation between percent increments in AVP and increments in double product. Norepinephrine increased significantly with effort in both groups, but the levels attained were higher in Group I. In view of the known negative inotropic action of AVP and the trophic effect of angiotensin, we speculate that lower baseline AVP and higher PRA, together with inability of AVP to increase with effort, may be causally related to development of LVH. PMID- 8490596 TI - Effect of nicardipine treatment on carbohydrate and lipoprotein metabolism in patients with hypertension. AB - This study evaluated the effect of nicardipine, calcium channel blocker, monotherapy on blood pressure and metabolic changes. Various aspect of carbohydrate and lipoprotein metabolism were studied before and after 12 weeks of nicardipine treatment in 23 patients with mild to moderate essential hypertension. Nicardipine was well tolerated and induced a significant decrease (p < 0.001) in both systolic and diastolic blood pressure without any changes in heart rate. Plasma levels of fasting glucose, insulin, C-peptide and hemoglobin A1c, hepatic extraction of insulin were similar following nicardipine treatment. Plasma glucose and insulin responses to an oral glucose challenge did not change in association with nicardipine therapy. Although high density lipoprotein (HDL) cholesterol concentration increased slightly, it did not reach statistical significance. Total cholesterol and low density lipoprotein (LDL) cholesterol levels also increased insignificantly. LDL triglyceride and very low density lipoprotein (VLDL) triglyceride concentrations were higher marginally, which resulted in slightly but insignificantly increase in total triglyceride concentration in association with nicardipine monotherapy for 12 weeks. In conclusion, treatment of patients with mild to moderate hypertension with nicardipine led to lower blood pressure effectively while had no significant influence on carbohydrate and lipoprotein metabolism. PMID- 8490597 TI - Role of insulin in the pathogenesis of hypertension associated with glucose intolerance. AB - The role of insulin in the pathogenesis of hypertension was explored in normal men and male patients with impaired glucose-tolerance. They were classified as normal (n = 94), borderline (n = 164), impaired tolerance (IGT, n = 104), or diabetes mellitus (n = 100) according to their response to an oral 75g glucose challenge. Besides routine laboratory examinations, fasting immunoreactive insulin and post-glucose insulin levels at 30 minutes were measured. Patients with impaired glucose tolerance were older and more obese than the normal subjects. Serum cholesterol and triglyceride concentrations increased with severity of the glucose tolerance impairment. However, renal function, as estimated by blood urea nitrogen levels did not differ among these four groups. Multiple regression analysis revealed that blood pressure correlates significantly with the obesity index, blood glucose, serum cholesterol and serum insulin in all four groups. Among these groups, the partial F ratios for the obesity index were the greatest in both normal and diabetic groups, but in both borderline and IGT groups those for insulin were the greatest. These results indicate that in patients with impaired glucose tolerance is hypertension associated more closely with hyperinsulinemia than it is in normal subjects or diabetic patients. PMID- 8490599 TI - Stretched to the limit. PMID- 8490600 TI - The need for terms and conditions. PMID- 8490598 TI - Renin gene nucleotide sequence of coding and regulatory regions in Dahl rats. AB - Renin alleles in the Dahl salt-hypertension sensitive (S) and Dahl salt hypertension resistant (R) rats are known to strongly cosegregate with blood pressure. The purpose of this work was to look for structural differences in the S and R renin alleles that could account for the cosegregation result. The nucleotide sequences determined for the coding region and the 5'-flanking regulatory region for the renin gene of S and R rats were identical. There were some minor nucleotide changes in selected regions of the 1st and 8th introns that were sequenced, but these were unlikely to be of functional importance. The remaining possible reasons for the cosegregation of blood pressure with renin alleles in Dahl rats are differences in renin regulatory elements out of the immediate 5'-flanking area, or differences in alleles at an unknown closely linked locus. PMID- 8490601 TI - Extracting consent. PMID- 8490602 TI - Getting the message across. PMID- 8490604 TI - Credit for the future. PMID- 8490603 TI - Handling food safely. PMID- 8490605 TI - The changing role of day hospitals. PMID- 8490606 TI - Preventing constipation. PMID- 8490607 TI - The Institute of Human Ageing. PMID- 8490609 TI - People, not parcels. PMID- 8490608 TI - A question of age. PMID- 8490610 TI - Old and cold in Moscow. PMID- 8490611 TI - Politics in focus. PMID- 8490612 TI - Power to pensioners. PMID- 8490613 TI - As I was saying.... PMID- 8490614 TI - Quality of life among children in the Nordic countries. AB - Quality of life (QOL) is a concept with no generally accepted definition. Most clinical studies have had an individual approach where demographic and socio economic population aspects have not been considered. QOL has hardly ever been used in studies of children. In this study QOL is defined as the essential resources of a child population, expressed in external, inter-personal and personal conditions. Both objective conditions and the corresponding subjective perceptions are included. A model for an empirical application is demonstrated on a random sample of 15,000 children in the five Nordic countries. The data were collected in a questionnaire mailed to the families of the children. The QOL was analysed in a normative way, where a base value was defined for each variable and the conditions of the children were compared to a Nordic standard for children's QOL. The results showed that children in the Nordic countries have a high QOL. The differences between the countries were rather small. Children in Sweden had the highest QOL, closely followed by children in Denmark and Norway, while children in Finland were in an intermediate position and the Icelandic children had the lowest QOL, mainly due to a lower level of satisfaction. This study can be considered as a base line study which later can be used in studies of time trends or in comparisons of groups of children such as children with special needs. PMID- 8490615 TI - Using patient reports to assess health-related quality of life after total hip replacement. AB - Data on disease severity, co-morbidity, and process of care were obtained from the medical records of 356 patients without rheumatoid arthritis undergoing a first unilateral total hip replacement at four teaching hospitals in California and Massachusetts. Socio-demographic characteristics, functional status prior and subsequent to hospitalization, and improvement in health status were measured with a patient questionnaire 12 months after discharge. Completed questionnaires were received from 284 patients, a response rate of 79.8%. The questionnaire was acceptable to patients, reliable, and had good construct validity. The data indicate substantial benefits from hip arthroplasty. As expected, pre-surgical functioning was a strong predictor of outcomes 1 year after surgery. Controlling for pre-surgical functioning, age was not related to outcomes. PMID- 8490616 TI - The Swedish Health-Related Quality of Life Survey (SWED-QUAL). AB - We present a Swedish Health-Related Quality of Life Survey (SWED-QUAL) that was adapted from measures used in the Medical Outcome Study (MOS). The development of these measures spans more than 20 years and their reliability and validity have been extensively tested. The SWED-QUAL consists of 61 items that form 11 multi item scales tapping aspects of physical, mental, social and general health. The instrument was mailed in 1991 to a random stratified sample of 2,366 individuals from the Swedish general population aged 18-84 years and to a stratified random sample of 2,349 individuals who had been seriously injured in a traffic accident. The response rates were 61% and 59%, respectively. Telephone follow-up of non responders indicate that most of those tended to have a better health-related quality of life than responders. The SWED-QUAL satisfied all of the psychometric criteria that were evaluated. Multitrait scaling provided strong support for item discrimination. Cronbach's alpha exceeded 0.78 for all scales. Scores tended to be lower among older than younger people, and among females compared to males. The good response rate indicates that the content of the SWED-QUAL is considered relevant by people at large, that the results from the general population sample could be used for comparisons with other samples and the instrument used for further studies of the effectiveness of a broad spectrum of medical interventions. PMID- 8490617 TI - cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young. AB - Complementary DNA clones encoding human cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) (PEPCK)] were isolated from a human kidney cDNA library. The nucleotide sequence of the 2.7 kb insert of one of these clones indicates that human PEPCK is a protein of 622 amino acids whose sequence shows 90% identity with that of the cognate rat enzyme. The human PEPCK gene (PCK1) was isolated by hybridization using a fragment of the hPEPCK cDNA as a probe. PCK1 was mapped to human chromosome 20 using DNA from a panel of reduced human-hamster somatic cell hybrids. This assignment was confirmed using fluorescence in situ chromosomal hybridization which localized PCK1 to chromosome 20, band q13.31. A simple tandem repeat DNA polymorphism in the 3'-untranslated region of the mRNA was characterized and used to localize PCK1 relative to the gene responsible for a form of non-insulin-dependent (Type 2) diabetes mellitus called maturity-onset diabetes of the young (MODY). Linkage studies showed that PCK1 is not tightly linked to MODY in one large pedigree and exclude this diabetes candidate gene as the cause of MODY in this family. PMID- 8490618 TI - Analysis of factor VIII mRNA reveals defects in everyone of 28 haemophilia A patients. AB - Haemophilia A is a mutationally heterogeneous disease caused by defects in the large and complex factor VIII gene. Recent studies examining the putative promoter, all exons and most intron/exon boundaries have failed to detect mutations in half the patients with severe disease leading to hypotheses such as mutations in remote controlling regions or even in genes other than factor VIII. We have amplified the factor VIII gene (putative promotor, coding region and polyadenylation/cleavage signal region) in 8 fragments from reverse transcribed mRNA and genomic DNA. Any mutation is then located by chemical mismatch detection and characterised by direct sequencing. This rapid and efficient method has been fully successful and has revealed an unusual cluster of mutations causing severe disease. Of the 28 patients we have reported, 5 had mild or moderate disease and all had a missense mutation. Twenty-three patients were severely affected and 13 of these had different detrimental mutations that were fully characterised at the genomic DNA level. The remaining 10 patients all had mRNA with exon 22 not contiguous to exon 23. Since all exons were normal and so were the splice sites of intron 22, the mutation in these patients should be in the regions of intron 22 that were not screened. These results prove that all haemophilia A cases are due to mutations of the factor VIII gene where, unexpectedly, intron 22 seems to be the target of approximately 40% of the mutations causing severe haemophilia A. PMID- 8490619 TI - Families of mtDNA re-arrangements can be detected in patients with mtDNA deletions: duplications may be a transient intermediate form. AB - In three patients with mitochondrial DNA duplications, there are two additional re-arranged molecules derived from mitochondrial DNA. Two forms of closed circular deletions of mitochondrial DNA have been characterised in all three patients, one being a monomer, and the other a dimer. The junction fragments appear to be the same in the deletion and the duplication, suggesting that both re-arrangements arose from the same initial recombination event, followed by homologous recombination. Sequential muscle biopsy and cell culture studies suggest that the duplication is present only transiently in muscle and cloned fibroblast lines. The duplicated molecule could thus be an intermediate in the formation of the deletion. Evidence is presented for the presence of duplicated mtDNA in 6/11 patients known to have deletions of mitochondrial DNA in muscle, suggesting that this could be a general mechanism for major re-arrangements of mitochondrial DNA. There may be parallels between the families of re-arrangements found in plant mitochondrial DNA, and the three distinct re-arranged molecules described here. PMID- 8490620 TI - Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR. AB - A cDNA for Fanconi anaemia complementation group C (FACC) has recently been cloned. We have now isolated a yeast artificial chromosome clone containing the FACC gene, and used vectorette PCR to determine its exon structure. The 1674 nucleotide coding sequence of the gene is highly interrupted, and contains 14 exons ranging in size from 53-204 bp. All exon donor and acceptor splice sites fit well with consensus sequences. Knowledge of the FACC exon boundaries and adjacent intron sequences was used to design polymerase chain reactions for amplification of all 14 exons from genomic DNA. Characterisation of splice site mutations in Fanconi anaemia patients with abnormal FACC transcripts and screening of large numbers of patients for mutations by amplification of the coding sequence from genomic DNA will now be possible. PMID- 8490621 TI - Is the maintainance of the C-terminus domain of dystrophin enough to ensure a milder Becker muscular dystrophy phenotype? AB - The severe Duchenne muscular dystrophy (DMD) and the more benign Becker type (BMD) are allelic conditions, controlled by a defective gene at Xp21, caused by the absence (DMD) or a defect in quantity or quality (BMD) of the protein dystrophin. It has been suggested that the C-terminus domain of dystrophin is fundamental to ensure the proper protein sub-cellular localization and function. We wish to report our dystrophin findings in 4 among 142 DMD patients studied for DNA deletions and dystrophin analysis. Although they have a severe clinical course, a positive dystrophin immunofluorescence pattern was seen using C terminal antibody, and a dystrophin band of reduced molecular weight (corresponding to their DNA deletions), but which maintained the C-terminus was seen through Western blot (WB). Based on these findings, we suggest that in order to partially maintain its function, resulting in a milder phenotype, dystrophin may carry large internal deletions but in addition to the C-terminus, the region encompassing both the N-terminus and the proximal region of the rod domain cannot be absent. Therefore, the prognosis of a Becker phenotype in a young patient should be done with caution if based only on the presence or not of dystrophin. PMID- 8490622 TI - Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms. AB - Pregnant women over 35 years of age are routinely offered screening tests and karyotyping to detect Down syndrome and certain other aneuploidies because the risk of these disorders increases exponentially with maternal age. It is, however, only cost-effective to karyotype high-risk pregnancies and a substantial number of remaining aneuploidy cases go undetected. We describe a rapid, inexpensive method to detect trisomy using polymorphic small tandem repeat (STR) markers and the polymerase chain reaction (PCR) to amplify amniocyte DNA. STR patterns obtained on patients with trisomy 21, trisomy 18 and triplo-X syndromes are distinct from controls. Polymorphic trisomy genotypes either show three fragment peaks of equal intensity or two fragments at a 2:1 dosage ratio. In addition, Turner syndrome (45, X0) DNA can be distinguished from normal male DNA because it fails to amplify a Y-chromosome specific PCR marker yet contains only a single dose of X-specific STR markers. Quantitative analysis of peak heights and areas from STR markers show that the two peak patterns separate into completely non-overlapping groups. The high level of heterozygosity of most STR markers result in a predominance of heterozygous controls and trisomy patterns with multiple alleles, the easiest patterns to differentiate. Homozygosity, and hence an uninformative STR pattern, is more common in controls than in trisomy samples. We anticipate as few as three STR markers per chromosome should be over 99% informative. PMID- 8490623 TI - Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene. AB - The structure of the gene coding for iduronate sulphate sulphatase (IDS) has been determined. We have used exon to exon and vectorette PCR to identify 9 exons within the IDS gene and to characterise the surrounding intron sequences. The results of this study will be useful for the complete analysis of many mutations giving rise to Hunter syndrome. IDS is the first member of the group of lysosomal nonarylsulphatase genes for which the gene structure has been determined. It bears no relationship to the exon organisation of steroid sulphatase, despite the homology between these two proteins. This suggests that the division of the sulphatases into the two subgroups on the basis of substrate specificity is also reflected at the level of gene structure. PMID- 8490624 TI - Localization of seven new genes around the HLA-A locus. AB - A yeast artificial chromosome (YAC B30) with a 320 kb insert of genomic DNA which includes the HLA-A gene was used to screen a cDNA library of human duodenal mucosa. Seven cDNA clones were isolated which correspond to seven new non-HLA class I structural genes. These new genes are located within a region that may well contain the gene responsible for hemochromatosis and have therefore been named HCG I-VII (Hemochromatosis Candidate Gene). HCG I, III, V and VI are probably single copy genes, situated at 180, 155, 140 and 230 kb centromeric to HLA-A, respectively. HCG II, IV and VII present several copies: one copy of HCG II, one of HCG IV and one of HCG VII are centromeric to HLA-A (at 30, 70 and 100 kb respectively). Another copy of HCG IV is 20 kb telomeric to HLA-A. Each of the genes localized on the YAC B30 is associated with an CpG/HTF island. PMID- 8490625 TI - Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients. AB - The heterogeneity of mutations causing Tay-Sachs disease in non-Jewish populations requires efficient techniques allowing the simultaneous screening for both known and novel mutations. beta-hexosaminidase mRNA isolated from cultured fibroblasts of 19 Tay-Sachs patients (7 with adult or late onset form of the disease and 12 with infantile Tay-Sachs disease) was amplified by cDNA-PCR in two overlapping segments spanning the entire coding sequence. We used chemical mismatch cleavage (CMC), denaturing gradient gel electrophoresis (DGGE) and direct sequencing of amplified fragments displaying a cleaved product or an altered melting behavior to screen the HEX A gene for mutations and to determine their distribution and frequency in the non-Jewish Tay-Sachs patients. These methods allowed us to identify 31 out of 38 alleles studied (82%). In addition to 9 previously described mutations (the 4 bp insertion in exon 11, G to A transitions at codons 170, 269, 482, 499 and 504, C to T transition at codon 499 and 504 and a GT to AT transition at the donor site of intron 9), we have identified 10 novel mutations. These include 1 donor splice site defect in intron 6, 8 missense mutations at non-randomly distributed conserved residues and a 2 bp deletion in exon 4. These results confirm the extreme molecular heterogeneity of mutations causing Tay-Sachs disease in non-Jewish population. The strategy used should be profitable for identifying mutations in large genes and for diagnostic purposes. PMID- 8490626 TI - Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia. AB - A new rare mutant form of apolipoprotein C-II (apoC-II), designated apoC-IISF, was identified in three unrelated hyperlipidemic patients. The first was a Caucasian male with a total cholesterol (TC) of 313 mg/dl and total triglyceride (TG) of 282 mg/dl, the second an African-American female (TC 345 mg/dl, TG 203 mg/dl) and the third, an African-American male (TC 345 mg/dl, TG 1000 mg/dl). Each subject was found to be heterozygous for a G to A substitution in the codon for residue 38, resulting in a Lys for Glu exchange. This accounts for the increased pl value of 5.3. The third patient, in addition to apoC-IISF, had apoC II2, another charge variant. This was determined by DNA sequencing, confirming the Gln for Lys change at residue 55 previously predicted by analysis of peptide fragments in this laboratory. Similar Michaelis constants of activation and activation energies were observed when the ability of apoC-IISF to activate lipoprotein lipase was compared to normal apoC-II. This indicates that major changes in charge around residue 38 lack effect on the activation properties. The variant may be altered in some other property, such as lipid binding, but since the distribution of apoC-IISF revealed no simple co-inheritance with lipid levels, it is unclear to what extent it plays a role in the observed hyperlipidemia. The presence of other factors acting together with the variant may predispose to elevated lipid levels. PMID- 8490627 TI - G6PD Aures: a new mutation (48 Ile-->Thr) causing mild G6PD deficiency is associated with favism. PMID- 8490628 TI - Dinucleotide repeat polymorphism at the CRH gene. PMID- 8490629 TI - Dinucleotide repeat polymorphisms at the D13S192 and D13S193 loci. PMID- 8490630 TI - Three dinucleotide microsatellite polymorphisms on human chromosome 13. PMID- 8490631 TI - Tetranucleotide repeat polymorphism at the D11S488 locus. PMID- 8490632 TI - A short tandem repeat polymorphism at the endothelin 1 (EDN1) locus. PMID- 8490633 TI - Dinucleotide repeat polymorphism at the D5S178 locus. PMID- 8490634 TI - Dinucleotide repeat polymorphism at the D18S99 locus. PMID- 8490635 TI - Dinucleotide repeat polymorphism at the DXS573 locus. PMID- 8490636 TI - Disturbances in identity and self-regulation in bulimia nervosa: implications for a metaphorical perspective of "body as self". AB - This study investigates a metaphorical account of bulimia that proposes that bulimics lack a clearly defined sense of self, and subsequently utilize their physical bodies as a means of self-definition and regulation. Three major aspects of this perspective were assessed: identity disturbance; use of the binge and purge as means of emotional regulation; and sensitivity to interpersonal contact. Differences among bulimics, binge eaters, and normal controls were explored. Bulimics reported greater amounts of identity confusion, enmeshment, and overall instability in self-concept than normal controls and binge eaters. The binge led to an escape from self-awareness for bulimics, and the purge served to manage negative affect. Bulimics also showed greater sensitivity to interpersonal contact with positive people, and with their mother than both binge eaters and controls. Implications of the findings are discussed as well as future directions for research. PMID- 8490637 TI - Cluster B personality disorder characteristics predict outcome in the treatment of bulimia nervosa. AB - The Personality Disorders Examination (PDE) was administered to 71 bulimia nervosa patients at baseline assessment in a study comparing the effectiveness of cognitive-behavioral treatment with desipramine or the combination of both treatments. Personality disorder subscales were combined into single DSM-III-R cluster scores. A high cluster B score (consisting of antisocial, borderline, histrionic, and narcissistic features) significantly predicted poor outcome at 16 weeks and was a better predictor of outcome than borderline personality characteristics alone or any other DSM-III-R cluster score or combination of cluster scores. In contrast pretreatment depression level, self-esteem, degree of dietary restraint, frequency of purging, and history of anorexia nervosa were not significantly related to outcome. At 1-year follow-up there was still a trend toward high cluster B scores predicting poor treatment outcome. Cluster B score was not significantly correlated with percentage of sessions attended nor did subjects with higher cluster B scores have a better outcome with either specific treatment. These results suggest that further investigation of alternative treatments is warranted with high cluster B individuals to determine if treatment effectiveness can be improved. PMID- 8490638 TI - Survival analysis of response to group psychotherapy in bulimia nervosa. AB - A reanalysis of treatment response and relapse was performed using survival analysis in a 12-week clinical trial of cognitive behavioral group psychotherapy for the treatment of bulimia nervosa. One hundred forty-three (143) bulimic women with high incidence of binge eating, self-induced vomiting, and/or laxative abuse were randomly assigned to one of four possible treatment conditions that consisted of a combination of two factors: (1) emphasis on abstinence (high and low), and (2) treatment intensity (high and low). "Initial" and "maintained" response to treatment based on "total" and "near" abstinence criteria were determined using self-reported binge eating, vomiting, and laxative use data. Results suggest that an emphasis on abstinence appears important in achieving initial abstinence, whereas intensity of treatment may be important in maintaining abstinence. PMID- 8490639 TI - An attempt to modify unhealthful eating attitudes and weight regulation practices of young adolescent girls. AB - This is the first long-term, controlled study evaluating the effectiveness of a prevention curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls. Nine hundred sixty-seven sixth and seventh-grade girls were randomized to experimental healthy weight regulation curriculum or no-treatment control classes. A prevention intervention was developed around three principal components: (1) Instruction on the harmful effects of unhealthful weight regulation; (2) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity; (3) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting. The intervention failed to achieve the hoped-for impact. We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only, there was a small albeit statistically significant effect on body mass index. These findings question the wisdom of providing a curriculum directed at all young adolescents, most of whom are not at risk to develop an eating disorder. Rather than targeting the entire population, a healthy weight curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls might better focus on "at risk" students. PMID- 8490640 TI - Confusion over the core psychopathology of bulimia nervosa. AB - There has been particular confusion concerning two aspects of the psychopathology of bulimia nervosa: dissatisfaction with body shape and overvalued ideas about shape and weight. Whilst these features are closely related, they are nevertheless distinct. Body shape dissatisfaction is commonly found in these patients but is not necessarily present; whilst the over-valued ideas about shape and weight are a necessary diagnostic feature. Analysis of the relationship between these two features and depressed mood and self-esteem showed that, in the course of treatment, change in body shape dissatisfaction was closely associated with change in mood; and change in the overvalued ideas was closely associated with change in self-esteem. This finding supports the distinction between these two facets of the core psychopathology of bulimia nervosa. PMID- 8490641 TI - Developmental onset of eating related color-naming interference. AB - The current study was an investigation into the possible developmental aspects of the "Eating Stroop" effect, as produced by non-eating disordered subjects. The subject pool comprised male and female subjects, ranging in age from 9 to 14 years. Their task was to color-name a series of Stroop arrays, comprising food related words, body shape-related words, and two sets of neutral matched control words. It was found that there were significant performance decrements for both food and shape-related words with the 14-year-old girls. The results indicated a possible color-naming decrement with food-related words for the 11-year-old girls, but not shape words. No color-naming decrements were found with the 9-year old group, or the male subjects. The results are interpreted in terms of cultural pressures on women to diet to attain an "ideal" body shape and the different developmental stages at which such pressures exert themselves. PMID- 8490642 TI - Self-denigratory beliefs following sexual abuse: association with the symptomatology of bulimic disorders. AB - Reported sexual abuse is associated with bulimic symptomatology. It has been suggested that this association might be due to impaired self-esteem. However, from the evidence to date, it appears that general self-esteem may be too "blunt" a construct, and that more specific psychological mediators need to be considered. This study compares the values of a measure of general self-esteem and a measure of specific self-denigratory beliefs consequent upon sexual abuse in predicting levels of eating psychopathology in eating-disordered women. Self esteem was associated with the level of general eating attitudes, whereas specific self-denigratory beliefs were associated with the frequency of vomiting. Neither variable adequately predicted the frequency of binging. PMID- 8490644 TI - Recent research bibliography. PMID- 8490643 TI - Kallmann's syndrome and anorexia nervosa: a diagnostic dilemma. AB - Kallmann's syndrome is a rare cause of primary amenorrhea, with impairment of release of gonadotropin-releasing hormone and anosmia. We present a case in which Kallmann's syndrome had been diagnosed, but who also fulfilled the diagnostic criteria for anorexia nervosa. We discuss the diagnostic dilemma. PMID- 8490645 TI - Adventures with adenovirus. PMID- 8490646 TI - Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. AB - Menkes disease is a lethal-X linked recessive disorder associated with copper metabolism disturbance. We have recently mapped two chromosome breakpoints related to this disease in a 1 megabase yeast artificial chromosome contig at Xq13.3. We now report the construction of a phage contig and the isolation of candidate partial cDNAs for the Menkes disease gene. The candidate gene expresses an 8 kb message in all investigated tissues, and deletions were detected in 16% of 100 unrelated Menkes patients. The deduced partial protein sequence shared the GMTCXXC motif with bacterial metal resistance operons, suggesting a potential heavy metal binding protein. These findings should lead to more accurate prenatal diagnosis of this severe disease and a better understanding of the cellular homeostasis of essential heavy metals. PMID- 8490647 TI - Isolation of a partial candidate gene for Menkes disease by positional cloning. AB - Menkes disease is an X-linked recessive disorder of copper metabolism resulting in death in early infancy. The gene has been mapped to band Xq13 based, in part, on a translocation breakpoint in a female with the disease, which was found to lie within 300 kilobases (kb) of the PGK-1 locus, allowing the isolation of a YAC clone spanning the breakpoint. Phage subclones from the breakpoint region were isolated and used to screen cDNA libraries. cDNA clones were found which detect an 8 kb transcript from normal individuals but show diminished or absent hybridization in Menkes disease patients. Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene. PMID- 8490648 TI - Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. AB - Waardenburg syndrome (WS) is a combination of deafness and pigmentary disturbances, normally inherited as an autosomal dominant trait. The pathology involves neural crest derivatives, but WS is heterogeneous clinically and genetically. Some type I WS families show linkage with markers on distal 2q and in three cases the disease has been attributed to mutations in the PAX3 gene. PAX3 encodes a paired domain, a highly conserved octapeptide and probably also a paired-type homeodomain. Here we describe a further three PAX3 mutations which cause WS; one alters the octapeptide motif plus the presumed homeodomain; a second alters all three elements and the third alters the paired box alone. The latter occurs in a family with probable type 2 WS, a clinical variant usually considered not to be allelic with type 1 WS. PMID- 8490649 TI - 'Kinky hair' disease sheds light on copper metabolism. PMID- 8490650 TI - A point mutation in the FMR-1 gene associated with fragile X mental retardation. AB - The vast majority of patients with fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at the cytogenetic level, and both amplification of the (CGG)n repeat and hypermethylation of the CpG island in the 5' fragile X gene (FMR-1) at the molecular level. We have studied the FMR-1 gene of a patient with the fragile X phenotype but without cytogenetic expression of FRAXA, a (CGG)n repeat of normal length and an unmethylated CpG island. We find a single point mutation in FMR-1 resulting in an lle367Asn substitution. This de novo mutation is absent in the patient's family and in 130 control X chromosomes, suggesting that the mutation causes the clinical abnormalities. Our results suggest that mutations in FMR-1 are directly responsible for fragile X syndrome, irrespective of possible secondary effects caused by FRAXA. PMID- 8490651 TI - Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. AB - We have performed mRNA in situ hybridization studies and northern blot analysis in the mouse and human, respectively, to determine the normal gene expression patterns of FMR-1. Expression in the adult mouse was localized to several regions of the brain and the tubules of the testes, which are two of the major organs affected in fragile X syndrome. Universal and very strong expression was observed in early mouse embryos, with differentially decreasing expression during subsequent stages of embryonic development. The early embryonic onset and tissue specificity of FMR-1 gene expression is consistent with involvement in the fragile X phenotype, and also suggests additional organ systems in which clinical manifestations of reduced FMR-1 gene expression may occur. PMID- 8490652 TI - Behavioural disorders: lessons in linkage. PMID- 8490653 TI - A recombination-based assay demonstrates that the fragile X sequence is transcribed widely during development. AB - To identify transcribed sequences rapidly and efficiently, we have developed a recombination-based assay to screen bacteriophage lambda libraries for sequences that share homology with a given probe. This strategy determines analytically whether a given probe is transcribed in a given tissue at a given time of development, and may also be used to isolate preparatively the transcribed sequence free of the screening probe. We illustrate this technology for the fragile X sequence, demonstrating that it is transcribed ubiquitously in an 11 week fetus, in a variety of 20 week human fetal tissues, including brain, spinal cord, eye, liver, kidney and skeletal muscle, and in adult jejunum. PMID- 8490654 TI - Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. AB - The hypothesis that chromosomal region Xq27-28 harbours a gene for manic depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8 G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders. PMID- 8490655 TI - Large deletions and other gross forms of chromosome imbalance compatible with viability and fertility in the mouse. AB - Large deletions and other gross forms of chromosome imbalance are known in man but have rarely been found in the mouse. By screening progeny of spermatogonially irradiated male mice for a combination of runting and other phenotypic effects, we have identified animals that have large deletions comprising from 2.5-30 percent of the length of individual chromosomes, or other major chromosome changes, which are compatible with viability and fertility. Certain chromosome regions appear particularly susceptible to the generation of viable deletions and this has implications for radiation mutagenesis studies. Correlations with human deletions are also indicated. PMID- 8490656 TI - Are X-linked cutis laxa and Menkes disease allelic? PMID- 8490657 TI - Neurofibromatosis type 1 gene mutations in neuroblastoma. AB - The introduction of human chromosome 17 suppresses the tumourigenicity of a neuroblastoma cell line in the absence of any effects on in vitro growth and the neurofibromatosis type 1 (NF1) gene may be responsible. Here we report that 4 out of 10 human neuroblastoma lines express little or no neurofibromin and that two of these lines show evidence of NF1 mutations, providing further proof that NF1 mutations occur in tumours that are not commonly found in NF1 patients. We also show that NF1 deficient neuroblastomas show only moderately elevated ras-GTP levels, in contrast to NF1 tumour cells, indicating that neurofibromin contributes differently to the negative regulation of ras in different cell types. PMID- 8490658 TI - Evidence for a new tumour suppressor locus (DBM) in human B-cell neoplasia telomeric to the retinoblastoma gene. AB - Roughly 25% of human B-cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozygous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B-cell malignancy. This locus is located at least 530 kilobases telomeric to RB1. PMID- 8490659 TI - Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. AB - Menkes disease is an X-linked disorder of copper transport characterized by progressive neurological degeneration and death in early childhood. We have isolated a candidate gene (Mc1) for Menkes disease and find qualitative or quantitative abnormalities in the mRNA in sixteen of twenty-one Menkes patients. Four patients lacking Mc1RNA showed rearrangements of the Menkes gene. The gene codes for a 1,500 amino acid protein, predicted to be a P-type cation transporting ATPase. The gene product is most similar to a bacterial copper transporting ATPase and additionally contains six putative metal-binding motifs at the N-terminus. The gene is transcribed in all cell types tested except liver, consistent with the expression of the Menkes defect. PMID- 8490660 TI - Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency. AB - The T-cell receptor (TCR) is composed of two glycoproteins (alpha and beta or gamma and delta) associated with four invariant polypeptides (CD3-gamma, delta, epsilon and zeta). The majority of TCR/CD3 complexes contain six polypeptide chains, and although there is some flexibility in the complex subunit stoichiometry the CD3-epsilon chain is central to CD3 core assembly and full complex formation. We have described previously defective expression of the TCR/CD3 complex in an immunodeficient child. We now report that two independent CD3-epsilon gene mutations present in the parents have segregated in the patient, leading to defective CD3-epsilon chain synthesis and preventing normal association and membrane expression of the TCR/CD3 complex. PMID- 8490661 TI - A human pseudoautosomal gene, ADP/ATP translocase, escapes X-inactivation whereas a homologue on Xq is subject to X-inactivation. AB - We report the cloning of a highly conserved pseudoautosomal gene on the human sex chromosomes. A cDNA clone was selected by crosshybridization with a microdissected clone from the chromosomal subregion Xp22.3. It encodes a previously characterized member of the ADP/ATP translocase family and plays a fundamental role in cellular energy metabolism. This gene, ANT3, is located approximately 1,300 kilobases from the telomere, proximal to the pseudoautosomal gene CSF2RA, and escapes X-inactivation. Interestingly, a homologue of ANT3, ANT2, maps to Xq and is subject to X-inactivation. These genes provide the first evidence of two closely related X-chromosomal genes, which show striking differences in their X-inactivation behaviour. PMID- 8490662 TI - Structure and physical map of 64 variable segments in the 3'0.8-megabase region of the human immunoglobulin heavy-chain locus. AB - We have constructed the physical map of the 0.8 megabase DNA fragment which contains the 3' 64 variable region (V) gene segments of the human immunoglobulin heavy chain (H) locus. The organization of the VH locus showed several features that indicate dynamic reshuffling of this locus. The sequenced 64 VH segments include 31 pseudogenes, of which 24 are highly conserved except for a few point mutations. Comparison of the 64 germline VH sequences shows that each VH family has conserved sequences, suggesting that there might be some genetic or selection mechanisms involved in maintenance of each family. The total number of the human VH segments was estimated to be about 120, including at least 7 orphons. PMID- 8490663 TI - Mechanical testing of urinary calculi. AB - The ability to predict how easily a stone will break in response to extracorporeal and intracorporeal lithotripsy would be advantageous for the urologist. In a study of fragments from 52 urinary calculi, in vitro microhardness results were found to increase for the series struvite to brushite. Ultrasound velocity measurements performed on 35 intact urinary stones showed a similar trend. This suggests that ultrasound velocity may be a useful indicator of stone strength and one which could be used in vitro to assist the planning of stone treatment. PMID- 8490664 TI - The recurrence rate of stones following ESWL. AB - With extracorporeal shockwave lithotripsy (ESWL) stone fragmentation and the potential creation of residual stones has become an integral part of the treatment strategy. Therefore true recurrence, regrowth and pseudo-recurrence determine the rate of new stone formation. In unselected series the overall recurrence rate after ESWL varies between 6% after 1 year and 20% after 4 years. The comparison between the recurrence rate after ESWL and the natural recurrence rate reveals that the results of ESWL are better than expected. Lithotripsy has no special effect on true stone recurrence, and even pseudo-recurrence is of minor clinical significance. PMID- 8490665 TI - Management of complex renal calculi. AB - The treatment of small renal pelvic and ureteric calculi can be performed with relative safety and efficacy using lithotripsy or an endourological method. There remains however, a proportion of stones that are resistant to these methods because of their anatomical position, physical composition or sheer size. To these stones must be applied a treatment strategy using the variety of techniques to their maximum advantage. This article aims to review the accumulated experience on the management of these more complex urinary calculi. PMID- 8490666 TI - Consensus of lithotriptor terminology. AB - The case for consensus of lithotriptor terminology is presented. An number of definitions are proposed, and it is suggested that general adoption of these terms in reporting of treatment would make it easier to compare results obtained in different centres and with different machines. PMID- 8490667 TI - Experimental basis of shockwave-induced renal trauma in the model of the canine kidney. AB - Using the new electromagnetic shockwave source of the Modulith SL 20 shockwave induced renal trauma was evaluated by acute and chronic studies in the the canine kidney model. In a further study the electromagnetic shockwave source of the Lithostar Plus Overhead module was tested. Overall, 92 kidneys were exposed to shock waves coupled either by water bath (Modulith lab type) or by water cushion (Modulith prototype, Lithostar Overhead) under ultrasound localization. The generator voltage ranged between 11 and 21 kV, the number of impulses between 25 and 2500. After application of 1500/2500 shocks the extent of the renal lesion depended strictly on the applied generator voltage and was classified into 4 grades: Grade 0, no macroscopic trauma detectable (at 11-12 kV); grade 1, petechial medullary bleeding (at 13 kV); grade 2, cortical hematoma (at 14-16 kV); and grade 3, perirenal hematoma (17-20 kV). Whereas at low and medium energy levels the number of shocks played only a minor role, at maximal generator voltage (20 kV) even 25 impulses induced a grade 2 and 600 shocks a grade 3 lesion, emphasizing the importance of shockwave limitation in the upper energy range. In shockwave-induced renal trauma a vascular lesion was predominant and cellular necrosis was secondary. Coupling with a water cushion resulted in a 15% 20% decrease in the disintegrative and traumatic effect, which was compensated for by increasing the generator voltage by 2 kV. Long-term studies showed complete restitution following grade 1 and 2 trauma, whereas after a grade 3 lesion a small segmental and capsular fibrosis without hyperplasia of the juxtaglomerular apparatus was observed. Based on the characteristic ultrasound pattern found in the first study, the threshold for induction of grade 1 lesion was investigated. With both lithotripters a wide range for induction of a grade 1 lesion (Modulith 234-411, Lithostar Plus 220-740) and also a significant overlapping with grade 0 and 2 lesions was seen at low energy settings (levels 2 4). In contrast, the range of shocks (Modulith 96-150, Lithostar Plus 90-142) and overlapping was minimal when high energy was used (levels 7-9). Finally, the disintegration-trauma coefficient combining the results obtained in a standard stone model with those of the canine kidney model was introduced. PMID- 8490668 TI - ESWL in situ or ureteroscopy for ureteric stones? AB - As documented by follow-up data on ureteric stones in 1259 ureteric units treated, ESWL in situ on advanced lithotriptors with stone location by ultrasonography and fluoroscopy was successful without any retrograde ureteric manipulation in 98% of stones in the upper, 71% in the iliac, and 84% in the distal ureter; 85% of the units were stone-free within 3 months: ancillary measures were needed in 11% and the stone-free state was reached after a median of 39 days. The results obtained with treatment after manipulation of the stone from the upper and mid-ureter by retrograde instrumentation were similar, but ancillary measures were needed in 20% of cases. Endoscopic management with rod lens ureteroscopes was highly efficient in the distal and mid-ureter, but involved a complication rate of about 11% and required general anaesthesia. In the upper ureter it was abandoned in favour of the two former methods. Endoscopic stone removal has been greatly facilitated by the development of ultrathin, semirigid ureteroscopes 6.2-9 F in diameter, as well as by laser and pneumatic lithotriptors that operate through their minute working ports. Of the stones impacted in 127 ureteric units, 97% were successfully managed at the first attempt, involving an overall complication rate of 6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490669 TI - The scientific basis of calcium oxalate urolithiasis. Predilection and precipitation, promotion and proscription. AB - The documentation of no other human disease threads as far into antiquity as that of urinary stones. However, despite this arcane history and the development of novel means of treating the condition, the basic mechanisms of stone formation and the identity of indicators of recurrence remain largely shrouded in uncertainty. This review is concerned with what scientific information is known about the cause and formation of calcium oxalate stones--the most common component of human uroliths. Stone pathogenesis can be broadly divided into two main processes: (1) nucleation of insoluble crystals in urine and (2) retention of those crystals within the urinary tract. The first section of the article presents the various factors that are known or surmised to influence the likelihood that crystals will nucleate within the renal collecting system, and these are considered from the perspective of both their relation to metabolic disorders and their usefulness as diagnostic and therapeutic indicators. A discussion of factors that may influence the probability that newly formed crystals will be retained within the nephron forms the second part of the review. In developing this more mechanistic aspect of the disease the epitaxy, matrix and inhibitor theories of stone formation are presented, with particular emphasis being placed on their relation to crystal nucleation, growth or aggregation, and experimental evidence both for and against the hypotheses are discussed. PMID- 8490670 TI - The detection of prostatic carcinoma. 4- or 7-MHz transrectal ultrasonography? AB - In this prospective study a comparison of 4-versus 7-MHz transrectal ultrasonography for the detection of prostatic carcinoma is reported. A total of 150 prostates were biopsied due to suspicion of malignancy arising at either digital rectal examination, 4- and/or 7-MHz transrectal ultrasonography, or elevated serum prostate-specific antigen levels. Malignancies of the prostate were detected in 68 of the 147 eligible biopsy core specimens. The results show only marginal differences in the sensitivity, specificity, and predictive values for the two transducers. PMID- 8490671 TI - The effect of stones on renal and ureteric physiology. AB - The effect of calculi on renal and ureteric function is the result of a complex sequence of pathophysiological events triggered by obstruction. The degree of impairment of renal function resulting depends on whether the obstruction is partial or complete, is unilateral or bilateral, is complicated by infection or not and how and when it is relieved. This review will look at these interacting factors and particularly on the effects of various treatment modalities ranging from open techniques to minimally and non-invasive interventions. PMID- 8490672 TI - Decline and unevenness of infant mortality in Salvador, Brazil, 1980-1988. AB - Data relating to infant mortality in Salvador, Brazil, were analyzed in order to determine how infant mortality evolved in various parts of the city during the period 1980-1988. This analysis showed sharp drops in the numbers of infant deaths, proportional infant mortality (infant deaths as a percentage of total deaths), and the infant mortality coefficient (infant deaths per thousand live births) during the study period despite deteriorating economic conditions. It also suggested that while these declines occurred throughout the city, the overall distribution of infant mortality in different reporting zones remained uneven. Among other things, these findings call attention to a need for further investigation of the roles played by various health measures (including immunization, control of respiratory and diarrheal diseases, encouragement of breast-feeding, and monitoring of growth and development) and of reduced fertility (resulting from birth spacing, use of contraceptives, and female sterilization) in bringing about declines in infant mortality during hard economic times. PMID- 8490674 TI - Genetic evidence of a species complex in Anopheles pseudopunctipennis sensu lato. AB - This preliminary report provides information concerning genetic variation in the vector mosquito Anopheles pseudopunctipennis sensu lato that could have malaria control implications. Because of inconsistencies in malaria transmission patterns within geographic zones inhabited by this vector, the possibility that it represents a species complex was investigated. Hybrid crossing studies, electrophoretic analysis of enzyme variation, and DNA restriction studies were carried out in mosquitoes captured in nine areas of Mexico, Bolivia, and Peru. The findings demonstrated the existence of a species complex believed to have resulted from allopatric speciation. This research points to a need for establishing the geographic distribution of the newly recognized species because of their potential influence on malaria control. PMID- 8490673 TI - Determinants of the geographic variation of invasive cervical cancer in Costa Rica. AB - The incidence of cervical cancer in Costa Rica is about twice as high in the coastal regions as in the interior. To study these regional variations, we used data from a 1986-1987 case-control study of 192 Costa Rican women with invasive cervical cancer and 372 controls. Risk factors identified included the following: The study participant's (1) number of sexual partners, (2) age at first sexual intercourse, (3) number of live births, (4) presence of type 16/18 human papillomavirus (HPV) DNA, (5) venereal disease (VD) history, (6) Pap smear history, and (7) socioeconomic status. The adjusted relative risks (RR) and 95% confidence intervals (CI) for each of these risk factors were as follows: (1) > or = 4 vs. 1 sexual partner: RR = 2.0, 95% CI = 1.1-3.5; (2) age of initiation < or = 15 vs. > or = 18 years: RR = 1.5, 95% CI = 0.9-2.5; (3) > or = 6 vs. < or = 1 live birth: RR = 1.7, 95% CI = 0.7-3.9; (4) HPV 16/18 DNA in cervix: RR = 2.8, 95% CI = 1.9-4.2; (5) VD history: RR = 2.2, 95% CI = 1.2-4.0; (6) no Pap smear: RR = 2.4, 95% CI = 1.5-3.8; and (7) low socioeconomic status: RR = 2.0, 95% CI = 1.2-3.2. The population-attributable risks related to HPV detection, four or more sexual partners, six or more live births, no prior Pap smear, and low socioeconomic status were 39%, 38%, 29%, 23%, and 22%, respectively. Several of the sexual and reproductive risk factors were relatively more prevalent in the high-risk region, but Pap screening and detection of HPV were equally prevalent in the high-risk and low-risk regions. Though differences in screening quality (laboratory and follow-up) may have been involved, we conclude that the observed regional differences reflect behavioral more than screening differences. This suggests that screening programs should be more aggressive in the high-risk area, given the more frequent occurrence of the disease there. Failure to detect a higher prevalence of HPV in the high-risk region could reflect weaknesses in the in situ hybridization test employed. Alternatively, cofactors may have to be present in order for HPV to exert its role in cervical carcinogenesis. PMID- 8490675 TI - Breast-feeding patterns in nine Latin American and Caribbean countries. AB - This article uses data from demographic and health surveys carried out in nine Latin American and Caribbean countries between 1984 and 1988 to compare breast feeding patterns in those countries, where findings indicate that 6% to 23% of the infants are not breast-fed beyond two months of age. Although wide variations in breast-feeding patterns occurred, a number of general trends were noted. To begin with, the mean rate of breast-feeding declined relatively fast in one group of countries (Brazil, Colombia, the Dominican Republic, Mexico, and Trinidad and Tobago), where half the infants surveyed had been weaned from the breast well before their first birthday. This differs from the situation found in the other four countries (Bolivia, Guatemala, Ecuador, and Peru), where half the infants were still being breast-fed during their second year of life. Within each of the nine countries, the mean breast-feeding duration was longer in rural than in urban areas and among women with relatively low levels of education. The direction of these relationships was similar when analyses were performed across countries. In addition, a strong inverse relationship was found between the percentage of births attended by health workers in the countries surveyed and the mean duration of breast-feeding in those countries. PMID- 8490676 TI - Attitudes and practices of pesticide users in Saint Lucia, West Indies. AB - This article reports the results of a Saint Lucia survey, part of a larger program, that was the first to document the prevalence of suboptimal safety practices among vector control and farm workers using pesticides in the English speaking Caribbean. Among other things, the survey found that many of 130 pesticide users surveyed were unaware that the skin and eyes were important potential routes of absorption. Over a quarter said they had felt ill at some point as a result of pesticide use. About half the respondents said they had received more than "introductory" training in safe pesticide use, and most said they always found labels or directions affixed to pesticide containers. However, about half said they never or only sometimes understood the labels, and many of those who said they understood did not always follow the instructions. About a quarter of the smokers said they smoked while using pesticides; about a sixth of the survey subjects said they ate food while using pesticides; and over 60% said they never wore protective clothing. PMID- 8490677 TI - Use of geographic information systems in control programs for onchocerciasis in Guatemala. PMID- 8490678 TI - Women's living conditions and maternal mortality in Latin America. PMID- 8490679 TI - Oswaldo Cruz and the flowering of public health in Brazil. PMID- 8490680 TI - Regional plan for investment in the environment and health. PMID- 8490681 TI - Health services system in Dominica. PMID- 8490682 TI - Declaration of Olympia on nutrition and fitness. PMID- 8490683 TI - Cardiac surgery in older people. PMID- 8490684 TI - An MD for Europe? PMID- 8490685 TI - Management of respiratory failure. AB - Hypoxaemia and hypercapnia are common clinical problems. A clear understanding of the diseases and pathophysiological processes that cause respiratory failure is important in making decisions about the concentration of oxygen to give, the type of face-mask to use, and the place of artificial ventilation. PMID- 8490686 TI - The ECG made difficult. PMID- 8490687 TI - Near infrared spectroscopy in fetal monitoring. AB - Fetal monitoring using near infrared spectroscopy offers the first realistic prospect of documenting real-time changes in fetal cerebral oxygenation during labour. This article explores the technical background, presents some of the results obtained and speculates on potential future developments. PMID- 8490688 TI - Acute tumour lysis syndrome. AB - Acute tumour lysis syndrome results from a rapid massive release of cellular breakdown products consequent upon tumour cell death following effective therapy. This may overwhelm normal excretory mechanisms, resulting in metabolic disturbance which can lead to sudden death or prolonged morbidity from renal impairment. PMID- 8490689 TI - Charcoal haemoperfusion in drug intoxication. AB - Charcoal haemoperfusion will remove many toxins, and appears to be an attractively simple technique for doctors experienced in haemofiltration. The pharmacokinetics of most compounds and the overriding importance of supportive care do, however, relegate the technique to one of minor importance. PMID- 8490690 TI - Moclobemide: a reversible inhibitor of monoamine oxidase type A. AB - The search for the ideal antidepressant continues. Moclobemide, the first reversible inhibitor of monoamine oxidase type A to enter widespread clinical use, has a number of advantages over traditional monoamine oxidase inhibitors and represents a valuable addition to the antidepressant armamentarium. PMID- 8490691 TI - Congenital Langerhans cell histiocytosis (histiocytosis X). PMID- 8490692 TI - Management of an abnormal smear: 2. AB - While large loop excision of the transformation zone is not a difficult technique, important principles must be considered to avoid complications. This article presents practical advice to deal with most circumstances that may arise. Postoperative protocols and efficacy are also covered. PMID- 8490693 TI - Centoxin: the full story of its withdrawal. PMID- 8490694 TI - Centoxin: the full story of its withdrawal. PMID- 8490695 TI - Microsurgical reconstruction of distal digits following mutilating hand injuries: results in 121 patients. AB - From 1982-1989, 152 mutilated distal digits were reconstructed with microsurgical foot tissue transfers in 121 patients. These various foot tissues included wrap around flaps or pulp from the great toe, second toe, or third toe, as well as partial toe, nail, web space skin, and other portions of the foot. The reconstructions were carried out primarily and secondarily in 78 and 74 patients respectively. The immediate success rate was 98%. Most of the patients were satisfied with both the cosmetic appearance and the functional result. This relatively minor microsurgical foot tissue transfer proved to be an ideal reconstructive option for distal digital defects. PMID- 8490696 TI - Fingertip replantation with an efferent A-V anastomosis for venous drainage: clinical reports. PMID- 8490697 TI - Aesthetic treatment of Romberg's disease: experience with 35 cases. AB - Our experience with dermis-fat free flaps and conventional reconstructive procedures for 35 patients with Romberg's disease over a 7-year period is presented. The groin flap was used for increasing volume in 33 cases, the scapular flap in 3 cases, and 2 were treated with the latissimus dorsi free flap. To achieve better contour, secondary procedures such as defatting of the flap, pedicled temporal fascial flaps, cartilage and bone grafts, orthognathic surgery, and other conventional aesthetic procedures were performed in 32 patients. Excellent results were achieved in 9 mildly deformed patients, in 12 out of 16 moderately, and in 3 out of 10 severely affected patients. Four moderate and 5 severe cases were classified as good results. Poor results were achieved in 2 severe cases. PMID- 8490698 TI - Midface advancement by gradual distraction. AB - Midface osteotomy was performed on 5 young adult sheep aged 10-12 months. In 4 animals midface advancement by gradual distraction was performed using an external device; one animal served as a control. The midface was advanced by 2 mm per day for 21 days. The amount of advancement was 36 mm in the nasofrontal area and 43 mm on the lateral aspect of the maxilla. After the period of active distraction the midface was maintained with external fixation for an additional 6 weeks to allow for ossification. Radiographs were obtained immediately postoperatively, after 21 days of distraction, and at the end of the 6 week fixation period. New bone formation in the distracted area was obvious radiographically, clinically and histologically. In conclusion, midface advancement by osteotomy and gradual distraction is possible in the sheep model and may offer controlled correction of deformity, obviating the need for the bone grafting. PMID- 8490699 TI - Fractures of the frontal sinus: a rationale of treatment. AB - There is still controversy on the management of frontal sinus fractures, as the optimal method of treatment has not been developed yet. Based on experience with 71 patients we formed a protocol, the basic principles of which are outlined here. In cases of posterior wall fractures the sinus was either cranialised or it was obliterated down to the nasofrontal duct. Anterior table fractures were reduced, defects were reconstructed and the sinus was drained via the nose for 4 6 weeks. Autologous graft material was always used for all reconstructive purposes. Meningitis occurred directly after the operation in 2 patients and a mucopyocele of the sinus with osteomyelitis of the frontal bone 1.5 years postoperatively in another. No further early or long term sequelae originating from the sinus were seen. PMID- 8490700 TI - A preliminary report on one stage open tip rhinoplasty at the time of lip repair in bilateral cleft lip and palate: the Alor Setar experience. AB - This paper is a preliminary report on a strategy to perform open tip rhinoplasty at the time of lip repair in bilateral cleft lip and palate deformity. This method was devised to suit unique socio-economic circumstances in the Malaysian centre of Alor Setar. Of 8 cases having surgery in 1991, 7 returned for follow-up with results being documented photographically. It is concluded that this aggressive approach is justified in severe bilateral cleft lip and palate deformity because of the cost effectiveness of limiting the number of interventions. Furthermore, it provides optimally orientated nasal tip anatomy and reduces the social stigma of cleft lip nose appearance from the earliest possible time in the child's development. PMID- 8490702 TI - The effect of backing materials on keratinocyte autograft take. AB - A porcine model has been established to study keratinocyte autografts as a model of human keratinocyte grafting. Keratinocyte autografts were placed on 104 full thickness wounds in 13 pigs and backed with 3 dressings which varied in their ability to maintain an occlusive environment. Sixteen control wounds were ungrafted. No take was found using a backing of woven viscose and cotton gauze. Take was 20% at day 16 using a backing of woven viscose and paraffin gauze. Serial biopsies showed that keratinocytes frequently attached to the interstices of the viscose dressing and difficulty in detaching the viscose caused loss of epidermis. Hydrogel sheet backing made assessment at day 10 difficult because of wound hydration but dressing removal, enabling exudate evaporation, produced 22% take at day 13. The development of improved dressing techniques is certainly necessary for improved graft take. PMID- 8490701 TI - Prefabricated flaps for the head and neck: a preliminary report. AB - The authors present some clinical applications of the concept of flap prefabrication. Three cases are described where reconstructions around the head and neck were accomplished. The radial vascular territory of the forearm was selected for prefabrication of structures which were then transferred by microsurgical techniques. In two cases, a sensate flap was used, with nerve repair in the neck. PMID- 8490703 TI - Variable rejection patterns of cultured keratinocyte allografts in the rabbit. AB - There are many conflicting reports on the survival of cultured keratinocyte allografts (CKAs). Studies were performed in the rabbit model to elucidate further the fate of CKAs. Of 24 CKAs, 7 were identified as technical failures, 13 displayed classical macroscopic evidence of rejection with a prolonged mean survival time of 2.8 days, compared to non-cultured allograft controls (p < 0.01), and 4 failed to display typical macroscopic evidence of rejection. Furthermore, the time to eventual wound healing of the classically rejected CKAs were delayed by 6.0 days (p < 0.0001), compared to identical non-grafted control wounds. PMID- 8490704 TI - The Misti Gold bio-oncotic gel filled breast prosthesis: an acceptable alternative to silicone? AB - Concern about the use of silicone gel as a filler for breast prostheses has stimulated interest in other materials. We have evaluated the Misti Gold prosthesis which contains a "bio-oncotic" gel of low molecular weight Polyvinylpyrrolidone (PLASDONE 24AUK). Our experience of its use in breast augmentation is that the aesthetic results obtained with retromammary placement are inferior to those obtained from a silicone gel filled prosthesis. Nonetheless there are theoretical advantages for its use which will need to be considered in the light of recent regulatory decisions. PMID- 8490705 TI - The management of skin infarction after meningococcal septicaemia in children. AB - The clinical course and management of 21 children (12 females, 9 males; mean age 2.4 years) with skin necrosis secondary to meningococcal septicaemia is described. Skin necrosis was most commonly sited in the lower limbs (20 patients). Sixteen patients had multiple areas of involvement and amputation of the digits was required in 5 patients. One required an above knee amputation. Small areas of skin necrosis were managed conservatively (4 patients) but larger areas required debridement and grafting. Skin grafting was delayed in 15 patients and graft loss occurred in 8. Multiple grafting procedures were required in 6 patients. Scar revision was required in 6 patients. Nutritional support is also an important component of management. PMID- 8490706 TI - Clinical experience with the PLDL-1 (Pigmented Lesion Dye Laser) in the treatment of pigmented birthmarks: a preliminary report. AB - Twenty patients aged between 2 years and 17 years (mean 9 years) with pigmented birthmarks, mainly of the head and neck, were treated with the PLDL-1 laser (Pigmented Lesion Dye Laser--Candela Corporation, Wayland, Massachusetts, USA) which emits light with a wavelength of 510 nanometers and a pulse duration of 300 +/- 50 nano-seconds. Nine patients (45%) showed excellent results after a test patch was performed. Two patients (10%) showed some lightening of colour after initial test-patch. Six patients (30%) showed no improvement and 3 patients (15%) showed some hyperpigmentation at the test-patch sites which had not disappeared at 6 months follow-up. There was no change in the clinical behaviour at 6 months follow-up and no evidence of scarring was encountered. PMID- 8490707 TI - A new cutaneous flap: snuff-box flap. PMID- 8490708 TI - Excision of benign pigmented skin tumours by deep shaving. AB - Benign pigmented skin tumours are frequently removed by shave excision. There is little information as to how often the method achieves a complete excision of the lesion and how often the full thickness of the dermis is removed. 43 benign pigmented skin tumours, on the trunk and proximal parts of the limbs, were removed by deep shaving and the shaved areas were then removed by elliptical excision. The shave excision achieved complete tumour removal in 72% of the lesions and did not divide the dermis to fat junction in 63%. Both objectives were achieved in 46%. Shave excision of these lesions may be preferable to elliptical excision in sites where the incidence of hypertrophic scarring is high, as preservation of some thickness of the dermis may result in a more acceptable scar. PMID- 8490709 TI - The role of the clinical trial in the evaluation of cleft surgery. PMID- 8490710 TI - Wire sutures: an aid to locating nerves. PMID- 8490711 TI - Sebaceous naevus of Jadassohn and primary mediastinal lipomatosis. AB - A rare association of sebaceous naevus of Jadassohn and primary mediastinal lipomatosis is presented. These are two benign conditions that can have serious complications. PMID- 8490712 TI - Recurrence of intraoral squamous cell carcinoma at the base of nasolabial flaps used for intraoral reconstruction: a report of two cases. AB - The nasolabial flap has proved useful in facial and intraoral reconstruction. Two cases are presented where nasolabial flaps used for intraoral reconstruction were associated with tumour recurrence in the base of the nasolabial flap. PMID- 8490713 TI - Heparinised saline solutions. PMID- 8490714 TI - Central administration of corticotropin releasing factor induces long-term sensitization to D-amphetamine. AB - Corticotropin releasing factor (CRF) has been shown to initiate neuroendocrine and behavioral responses to stress. As stress and amphetamine (AMPH) show cross sensitization, we investigated the role of endogenous CRF in behavioral sensitization to D-AMPH. In order to evaluate the participation of the central action and the pituitary-adrenocortical (PA) stimulatory effect of CRF, we compared the effects of repeated intracerebroventricular (i.c.v.) administration of CRF (0, 0.5, 2.5 micrograms/2 microliters), which have central and neuroendocrine consequences, with those of repeated subcutaneous administration of CRF (0, 0.1, 0.5, 2.5 micrograms/250 microliters), doses which only stimulate the PA axis, on the development of sensitization to AMPH-induced motor activation administered 1 week later. Repeated i.c.v. administration of CRF induced a long lasting enhancement of the hyperactivity induced by 0.75 mg/kg peripheral administration of D-AMPH, whereas no sensitization to D-AMPH was observed following repeated subcutaneous administration of CRF. These results favor the hypothesis that a centrally mediated action of CRF is involved in the cross sensitization of psychostimulants and stress. PMID- 8490715 TI - Brain protein kinase C assay using MARCKS substrate reveals no translocation due to profound insulin-induced hypoglycemia. AB - Hypoglycemia sufficient to produce EEG isoelectricity or coma leads to neuronal death by an excitotoxic mechanism due to elevated extracellular levels of glutamate, aspartate and increased intracellular calcium. Since an elevated intracellular calcium concentration is known to translocate protein kinase C (PKC) from the cytosol to the membrane (a process thought to represent the in vivo activation of the enzyme), the objective of this investigation was to determine if calcium-dependent isoforms of PKC were translocated in specific brain regions of rats subjected to 40 min of insulin-induced hypoglycemic coma. The caudate nucleus and hippocampus (regions damaged by hypoglycemia showing extensive neuronal necrosis), and cerebellum (an undamaged, control region) of hypoglycemic rats were microdissected. Soluble and detergent (Triton X-100) solubilized particulate fractions were partially purified by DEAE-Sephacel chromatography. PKC activity in both fractions was then measured using a novel assay based on the calcium- and lipid (phosphatidylserine and diolein)-dependent phosphorylation of the specific substrate myristoylated alanine rich C kinase substrate (MARCKS). The percentage distribution of PKC in the soluble and particulate (membrane-bound) fractions of all the brain regions from hypoglycemic rats was not significantly different from that in the control brains, indicating that 40 min of hypoglycemia does not result in PKC translocation as measured in subcellular fractions from brain tissue. PMID- 8490716 TI - Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. AB - The effects of local application of serotonin (5-HT) on extracellular levels of dopamine (DA) in the nucleus accumbens (N. ACC) were assessed using in vivo microdialysis. At a perfusate flow rate of 0.3 microliter/min the baseline dialysate concentration of DA was 2.1 +/- 0.7 nM (mean +/- S.E.M.; n = 5) and significantly increased to 142 +/- 18%, 220 +/- 47% and 332 +/- 35% of baseline when 0.1 microM, 0.2 microM and 0.4 microM concentrations of 5-HT were included in the perfusate. Perfusate 5-HT concentrations below 0.1 microM had no effect on dialysate DA. The in vivo dialysis efficiency for 5-HT was found to be 39 +/- 12%, and thus the concentrations of 5-HT reaching the extracellular space at the surface of the dialysis membrane were estimated to be 40, 80 and 160 nM for the 0.1, 0.2 and 0.4 microM 5-HT perfusates, respectively. The serotonin-induced increase in dialysate DA was attenuated by co-perfusion of 0.4 microM 5-HT with 4 microM concentrations of pindolol (a relatively non-specific 5-HT1 antagonist; 151 +/- 7% vs. 332 +/- 35% baseline dialysate DA for 5-HT/antagonist and 5-HT only perfusates, respectively), LY 53,857 (a specific 5-HT2 antagonist; 130 +/- 17% vs. 332 +/- 35%) and MDL 7222 (a specific 5-HT3 antagonist; 143 +/- 19% vs. 332 +/- 35%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490717 TI - Metabolism of inositol 1,4,5-trisphosphate in mouse brain due to decapitation ischemic insult: effects of acute lithium administration and temporal relationship to diacylglycerols, free fatty acids and energy metabolites. AB - Previous studies have shown that global cerebral ischemia induced by decapitation leads to the stimulated hydrolysis of poly-phosphoinositides. In this study, the decapitation model was used to further examine the temporal events related to metabolism of Ins(1,4,5)P3 and the release of diacylglycerols (DGs) and free fatty acids (FFAs) in the mouse brain. Since lithium administration is known to inhibit inositol monophosphatase activity in brain, the effects of acute lithium injection on Ins(1,4,5)P3 metabolism were also examined. Cerebral ischemia induced by decapitation of C57 Bl/6J mice resulted in transient increases of Ins(1,4,5)P3, Ins(1,4)P2 and Ins(4)P which peaked at 35, 65 and 125 s, respectively. The level of Ins(1)P, however, was not altered. Mice administered lithium by intraperitoneal injection (8 meq/kg for 4 h) gave rise to a 40- and 4 fold increase in levels of Ins(1)P, Ins(4)P, respectively, a 20% increase in levels of Ins(1,4)P2 but no apparent changes in the levels of Ins(1,4,5)P3. Decapitation also induced an increase in the levels of DGs and FFAs. Unlike the transient appearance of Ins(1,4,5)P3, however, DG levels increased steadily for 2 min and then reached a plateau whereas the FFAs showed a lag time of 35 s prior to a biphasic increase. During the initial 2 min after decapitation, there was a preferential increase in the DG species containing 18:0 and 20:4. Lithium administration did not alter the decapitation-induced release of DG and FFA. As expected, decapitation gave rise to a rapid decrease in the levels of phosphocreatine and ATP and the decline in ATP was marked by a transient appearance of ADP and a concomitant increase in AMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490718 TI - Tetrodotoxin does not affect circadian rhythms in neuronal activity and metabolism in rodent suprachiasmatic nucleus in vitro. AB - Single unit activity of suprachiasmatic nucleus (SCN) neurons recorded from hamster and rat hypothalamic slices in vitro exhibits a circadian rhythm in firing rate. Tetrodotoxin (TTX) produces electrical silence during the period of administration but has no effect on the oscillatory activity of the circadian pacemaker in both hamster and rat SCN. TTX does not affect either the phase of the rhythm in firing rate at any time of the circadian day, or that of the rhythm in glucose metabolism as demonstrated by the 2-deoxyglucose method. These data are in accord with the view that SCN neuron firing rate and glucose utilization is an expression of pacemaker activity but that pacemaker function is maintained in the SCN independent of neuronal function manifested by sodium dependent action potentials. PMID- 8490719 TI - Serotonin content is elevated in the dopamine deficient striatum of the weaver mutant mouse. AB - In the present study, we measured the striatal serotonin content of weaver and control mice at different ages. Overall, weaver mutant mice exhibited 50% more striatal serotonin than controls. Neither a rostrocaudal gradient nor an age effect was found for either genotype. An analysis of serotonin content across the dorsoventral extent of the striatum revealed that in the dorsal striatum of the weaver, serotonin content was increased 200%, and in the ventral striatum, the increase amounted to 50% relative to control mice. Serotonin immunocytochemistry also revealed an increase in the dorsal striata of weaver mice. The major increase in striatal serotonin content seen in the weaver striatum occurs in the same region that exhibits the severest dopamine depletion. This observation is consistent with the notion that the increase in serotonin levels may be secondary to the decrease in dopamine content and may play an adaptive or compensatory role. PMID- 8490720 TI - Serotonin 5-HT1 and 5-HT2 receptors in adult rat brain after neonatal destruction of nigrostriatal dopamine neurons: a quantitative autoradiographic study. AB - Neonatal destruction of nigrostriatal dopamine neurons by cerebroventricular injection of 6-hydroxydopamine (6-OHDA) results in a serotonin (5-HT) hyperinnervation of the rostral neostriatum in adult rat. Quantitative ligand binding autoradiography was used to compare the density of various 5-HT receptor subtypes in the adult brain of control and neonatally 6-OHDA-lesioned rats. 5 HT1A, 5-HT1B, 5HT1nonAB and 5-HT2 sites were labeled with [3H]8-OH-DPAT, [125I]cyanopindolol, [3H]5-HT and [125I]DOI, respectively, and measured in the rostral and caudal halves of neostriatum and selected forebrain or midbrain regions. 5-HT1A binding, measured after 6 months, was unchanged in all regions examined including the dorsal raphe nucleus. Three months after the lesion, 5 HT1B binding was increased throughout the neostriatum (30%), but also in the substantia nigra (50%) and globus pallidus (30%), suggesting an up-regulation and an increased axonal transport of these receptors in neostriatal projection neurons. 5-HT1nonAB binding was also increased throughout the neostriatum (40%) and in the substantia nigra (50%), but unchanged in the globus pallidus, as if this up-regulation preferentially involved striatonigral as opposed to striatopallidal neurons. 5-HT2 binding showed an even greater increase (60%), which was restricted to the rostral half of neostriatum and also seemed imputable to an up-regulation as heteroreceptors. Even though the exact cause(s) of these receptor increases could not be determined, their anatomical distribution suggested that they were somehow related to the initial dopamine denervation in the case of the 5-HT1B and 5-HT1nonAB receptors, and more tightly linked to the 5 HT hyperinnervation in the case of the 5-HT2 receptors. Such receptor changes could participate in adaptive mechanisms implicating other transmitters and behavioral disturbances observed in this particular experimental model. Interestingly, they could also account for an enhancement of neostriatal 5-HT function even in a condition where extracellular levels of 5-HT apparently remain normal because of increased uptake. PMID- 8490721 TI - Localization of immunoreactive glutamyl aminopeptidase in rat brain. I. Association with cerebral microvessels. AB - Glutamyl aminopeptidase (aminopeptidase-A, EC 3.4.11.7) is an ectoenzyme that selectively hydrolyses N-terminal glutamyl and aspartyl residues from oligopeptides, including (Asp1) angiotensin II. Here we sought to determine the distribution of glutamyl aminopeptidase (EAP) in rat brain. EAP was purified to homogeneity from rat kidney and polyclonal antiserum raised in rabbits. Immune serum inhibited EAP enzyme activity in kidney homogenates and labeled two major protein bands of M(r) = 136,000 and M(r) = 101,000 in immunoblots of kidney protein. EAP-like immunoreactivity was concentrated on kidney proximal tubule brush borders. Immunocytochemical staining of rat brain indicated that EAP-like immunoreactivity was primarily associated with cerebral microvessels. Positive staining was detected in microvessels ranging in size from capillaries up to vessels approximately 50 microns in diameter. Isolated cerebral microvessels had a 23-fold enrichment in EAP enzyme activity (193.1 +/- 40.4 nmol/mg protein/h) compared to brain homogenates. Finally, immunoblots of isolated cerebral microvessels resulted in a pattern of labeling similar to that seen with kidney homogenates. These results indicate that EAP activity in brain is primarily associated with cerebral microvessels, and suggest that EAP may be involved in the metabolism of circulating or locally formed peptides. PMID- 8490722 TI - Localization of immunoreactive glutamyl aminopeptidase in rat brain. II. Distribution and correlation with angiotensin II. AB - Glutamyl aminopeptidase (EAP, EC 3.4.11.7) selectively hydrolyzes N-terminal glutamyl and aspartyl residues from oligopeptides and is present in the brain. (Asp1)Angiotensin II (Ang II) is a substrate for EAP, and increasing evidence suggests that des(Asp1)angiotensin II (Ang III) is an active angiotensin peptide in the brain. To determine whether a relationship exists between EAP and Ang II/III in rat brain, we compared their immunocytochemical distributions. EAP-like immunoreactivity was localized primarily to the adventitial surface of cerebral microvessels throughout the forebrain. Endothelial cells, neurons and glial cells were not labeled. The immunocytochemical staining of microvessel adventitium with EAP antiserum was suggestive of labeling of perivascular pericytes since intravenous horseradish peroxidase resulted in a similar adventitial pattern of staining, in addition to pericyte cell bodies. EAP immunoreactivity was highest within circumventricular organs, areas known to contain high levels of Ang II receptors. Positively stained EAP microvessels were also concentrated in areas containing Ang II/III immunoreactive neurons or nerve terminals, including the hypothalamic paraventricular nucleus and the median eminence. The immunocytochemical localization of EAP suggests that it may be involved in a wide variety of functions within the brain, including: (i) metabolism of circulating peptides in brain areas devoid of a blood-brain barrier, (ii) metabolism of circulating peptides as a component of the blood-brain barrier, (iii) metabolism of intravascularly synthesized peptides, (iv) metabolism of hypothalamic peptides released into the portal circulation, (v) metabolism/conversion of neuronally released Ang II to Ang III in the interstitial space, and (vi) metabolism of neuronally released neuropeptides with vasoactive properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490723 TI - Calbindin-D28k immunoreactivity and selective vulnerability to ischemia in the dentate gyrus of the developing rat. AB - Hippocampal dentate granule cells normally express the calcium-binding protein calbindin-D28k and, in the adult, are the hippocampal neurons least vulnerable to an ischemic insult. We evaluated hippocampal structure 2-3 days after hypoxic/ischemic insult at postnatal day 7-10, and discovered that, unlike adult granule cells, developing granule cells were irreversibly injured. Localization of calbindin-D28k-like immunoreactivity (LI) revealed that the vulnerable cells were the immature granule cells at the base of the cell layer that were not yet calbindin-immunoreactive. Adjacent granule cells that did not die in response to the hypoxic/ischemic insult were calbindin-immunoreactive. Whether the lack of calbindin-LI in immature granule cells is causally related to their vulnerability, or is a coincidental reflection of cellular immaturity, remains to be determined. PMID- 8490724 TI - Co-expression of Fos immunoreactivity in protein kinase (PKC gamma)-positive neurones: quantitative analysis of a brain region involved in learning. AB - The expression of the gamma protein kinase C isoenzyme (PKC gamma) and of the c fos immediate early gene protein product Fos in the intermediate and medial hyperstriatum ventrale (IMHV) of day-old chicks was determined immunocytochemically. Previous research has shown that (a) there is a learning related increase in the expression of Fos in the IMHV of the chick after imprinting; (b) PKC gamma is expressed in neurones in most regions of the chick forebrain, including the IMHV. In the present study it was found that in imprinted chicks, 96.5% of neurones in the IMHV that expressed Fos also stained positively for PKC gamma. These results raise the possibility of a functional connection between PKC gamma activation and c-fos expression in neurones in general, and in particular in neurones in the IMHV that are involved in learning. PMID- 8490725 TI - A novel non-ataxic guinea pig strain with cerebrocortical and cerebellar abnormalities. AB - This is the first description of GS guinea pigs, a partially inbred, non-ataxic, albino Peruvian (long-hair) strain with abnormal motor behavior and seizures. GS guinea pigs show gross and microscopic cerebellar and microscopic cerebrocortical abnormalities compared to Hartley strain animals. There is little difference between GS and short-hair guinea pig strains in Purkinje cell function, electrically evoked Ca2+ transients or immune responsiveness. The GS strain may prove useful in studying altered functions of the cerebellum in human disease. PMID- 8490726 TI - Modulation of nicotinic acetylcholine receptor function in bovine adrenal chromaffin cells by thymopentin. AB - Thymopentin is a five amino acid peptide which corresponds to amino acids 32-36 of the thymic polypeptide thymopoietin. Previous work had shown that TP-5 could modulate responsiveness at the muscle-type nicotinic receptor. The present studies show that neuronal nicotinic receptor function, measured as radiolabelled noradrenaline release from bovine adrenal medullary cells, was attenuated by thymopentin. The pentapeptide exhibited specificity for nicotinic receptor evoked release, since thymopentin did not affect potassium-stimulated secretion of [3H]noradrenaline. It appears, therefore, that thymopentin antagonizes catecholamine release by specifically modulating nicotinic receptor responsiveness. PMID- 8490727 TI - Effects of electrical stimulation or local anesthesia of the rabbit's hypothalamus on the acute phase response. AB - The effects of electrical stimulation of the rostral hypothalamic region on the acute phase response (APR) were examined in rabbits. As indicators of APR, we measured changes in the plasma concentrations of iron, zinc, copper, and fibrinogen and changes in the red and white blood cell counts. Electrical stimulation of the rostral hypothalamic region near the preoptic and anterior hypothalamic region did not induce any aspect of the APR. However, stimulation near the anteroventral portion of the third ventricle (AV3V) induced responses that were, in part, opposite to those observed in the APR: an increase in the plasma concentration of zinc and a decrease in the circulating leukocyte count. Microinjections of procaine into the brain regions near the AV3V did not induce any changes in the plasma levels of trace metals and fibrinogen but increased the circulating leukocyte count. These results suggest that nonspecific stimulation or inhibition of the rostral hypothalamic region does not induce APR. PMID- 8490729 TI - Septal TRH in alcohol-naive P and NP rats and following alcohol challenge. AB - Regional brain content of TRH was evaluated in selectively bred alcohol preferring (P) and -nonpreferring (NP) rats before, during, and upon awakening from ethanol sedation. TRH content was significantly lower in both the medial and lateral septum of alcohol-naive P rats compared with alcohol-naive NP rats. Following a sedating dose of ethanol, P rats righted themselves sooner than NP rats. TRH content in the medial septum of P and NP rats was significantly higher when the rats regained their righting reflex. While sedated, TRH in the medial septum of P rats was insignificantly increased. These data are the first to show that endogenous TRH in the medial septum may be involved in arousal from drug induced sedation and that the events preceding arousal may occur sooner in P than in NP rats. In addition, innate differences in septal TRH may be associated with preference for ethanol. PMID- 8490728 TI - Acute and chronic effects of VMH lesions on circadian rhythms in food intake and metabolites. AB - In the dynamic phase, 3 weeks after surgery, food intake increased especially during the latter part of the light cycle in VMH-lesioned rats, and the difference between light and dark cycles disappeared. The rhythms of serum insulin, glucose, and triglyceride disappeared. Concentrations of glucose during the light cycle were lower than those of sham-operated rats, although concentrations of triglyceride and insulin were higher than those of sham operated rats at all times. In the static phase, 12 weeks after surgery, the difference of food intake between light and dark cycle appeared in VMH-lesioned rats, but the loss of rhythmicity for serum glucose, insulin, and triglyceride remained. Concentrations of glucose except early light phase and concentrations of triglyceride and insulin at all times were higher than those of sham-operated rats. VMH lesions thus abolished circadian rhythmicity in serum insulin, glucose, and triglyceride for a long period; however, the disturbed rhythmicity of food intake was reversible. PMID- 8490730 TI - Dopamine receptor antagonist blocks the release of glycine, GABA, and taurine produced by amphetamine. AB - The effects of systemic injections of amphetamine sulfate on the extracellular levels of glycine, GABA, and taurine in the neostriatum of awake rats were studied using a push-pull perfusion system. Amphetamine produced a dose-related increase in glycine levels. Amphetamine also produced an enhancement on GABA and taurine levels, although these increases did not follow a dose-related curve. The percentage increase of amino acids produced by the highest dose of amphetamine (5 mg/kg) at the peak effect was: GLY 235.9%; GABA 218%, and TAU 177%. All these effects were blocked by the D1-D2 dopamine receptor antagonist, haloperidol. It is suggested that dopamine, released by amphetamine, induces the release of inhibitory amino acid neurotransmitters in the neostriatum. These results are consistent with the hypothesis of dopamine playing a role of an amplifier of the activity of different neurochemical circuits. The results are also in accord with the idea that dopamine could mediate the neurotoxic effects produced by amphetamines through an interplay between excitatory and inhibitory amino acids. PMID- 8490731 TI - Impact of fetal nicotine exposure on development of rat brain regions: critical sensitive periods or effects of withdrawal? AB - Fetal nicotine exposure evokes alterations in central nervous system structural, neurochemical, and behavioral development. In the current study, the relative importance of critical developmental exposure periods and withdrawal were examined by infusing nicotine to pregnant rats using osmotic minipumps beginning on the fourth day of gestation. Infusions were confined to either the first 8 days (withdrawal on gestational day 13), to nearly all of gestation (withdrawal on gestational day 21), or throughout gestation and continued into the first 2 postnatal weeks. Maternal weight gain was retarded by nicotine, with a hierarchy corresponding to the duration of nicotine exposure. Similarly, fetal and neonatal body weights were unaffected in the group receiving the shortest duration of nicotine exposure, and were less affected by the intermediate infusion regimen than by the longest regimen; brain region weights were reduced significantly only with the longest regimen. Using ODC activity, a sensitive marker for altered brain cell development, we found little change in animals exposed to nicotine in early gestation and undergoing withdrawal on day 13. However, in the groups receiving nicotine through the end of gestation or through gestation and into the postnatal period, ODC activity was significantly elevated. These results indicate that withdrawal from nicotine contributes little, if any, effect either to the growth deficits or to abnormalities of brain cell development. Instead, the most important factor appears to be exposure within the developmental period corresponding to the proliferation of nicotinic receptors and the timing of receptor control of cell replication and differentiation. PMID- 8490732 TI - Stress-induced c-fos expression in the rat brain: activation mechanism of sympathetic pathway. AB - To clarify which brain regions are activated by stress, we used expression of the proto-oncogene, c-fos, as a marker. An increased number of neurons expressing Fos like immunoreactivity in their nuclei was observed in discrete brain regions, such as the lateral septum, midline nuclei of the thalamus, paraventricular hypothalamic nucleus, brain stem catecholaminergic, and serotonergic neurons, in response to pain or immobilization stress. Distribution patterns of Fos-like immunoreactive neurons were quite similar in animals subjected to pain or immobilization. Whether or not neurons projecting to the spinal cord to activate the sympathetic pathway express Fos-like immunoreactivity was examined by means of fluorescent double-labeling using fluoro-gold (FG) as a tracer. In the PVH, Fos-immunoreactive neurons were localized in the dorsal medial parvocellular part, although those projecting to the spinal cord were localized dorsally and ventrally. Less than 1% of Fos-positive neurons in this nucleus was colocalized with FG. Among fos-like immunoreactive catecholaminergic and serotonergic neurons in the brain stem, those in the A5 region and raphe pallidus projected to the spinal cord. PMID- 8490733 TI - Selective effects on CRF neurons and catecholamine terminals in two stress responsive regions of adult rat brain after prenatal exposure to diazepam. AB - Earlier work demonstrated that prenatal exposure to diazepam (DZ) selectively affected the noradrenergic (NE) terminals in the hypothalamus, leading to decreased basal NE levels, turnover rate, and release in adult offspring as well as altered responses to stressors in these NE projections. The exposure also affected plasma hormonal responses to stressors. In the present work, we used immunocytochemistry to study the effects of prenatal DZ exposure on NE terminals and on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. DZ exposure (2.5 or 10 mg/kg over gestational days 14-20) led to a decrease in dopamine-beta-hydroxylase (DBH) immunoreactivity (-ir) and a decrease in CRF-ir containing cells within the PVN of adult rats. The exposure also decreased DBH-ir in the ventral portion of the bed nucleus of the stria terminalis (BNST) but did not affect CRF-ir in the oval nucleus of BNST. Therefore, this study provides anatomic evidence that targeting benzodiazepine binding sites prenatally affects two neurotransmitter systems involved in responses to stressors. PMID- 8490734 TI - Spectral analysis and modelling of ACh and NE effects on shark nervus terminalis activity. AB - We investigated the effects of acetylcholine (ACh) and norepinephrine (NE) on activity in the nervus terminalis (NT) ganglion of the bonnethead shark (Sphyrna tiburo) using an in vitro preparation and whole nerve recordings. Spectral analysis indicated that ACh (10 and 100 microM) had a variable effect on the total spectral power of whole nerve activity but produced a consistent decrease in half power frequency (HPF; the median frequency of the power spectrum). Norepinephrine (10 microM) reduced baseline activity and total spectral power but produced an increase in HPF in all NT preparations. Computer simulations of extracellular recordings suggested a general explanation for these findings. Acetylcholine may have opposite effects on activity in two NT cell populations with axons in the central nerve trunk, increasing activity in cells whose axons have broad spikes (low spectral frequency) and decreasing activity in cells whose axons have narrow spikes (high spectral frequency). The NE effects are consistent with a decrease in activity of cells whose axons have broad spikes (low spectral frequency) and little or no change in cells whose axons have narrow spikes (high spectral frequency). The physiological data, together with the theoretical analysis, suggest that cholinergic and catecholaminergic neurotransmitter systems are active in the bonnethead NT ganglion, and that ACh and NE have different effects on two populations of ganglion cells. PMID- 8490735 TI - Effects of calcium and paired-pulse stimulation on hypoxia-induced hippocampal electrical changes. AB - The influence of calcium concentration changes (2 and 4 mM) and of the paired pulse stimulation (PPS) paradigm on the effects of hypoxia has been investigated in rat hippocampal slices. Because a high calcium concentration (4 mM) facilitates paired-pulse inhibition (PPI) at a 15-ms interpulse interval, the influence of hypoxia-induced effects were tested against calcium-induced PPI. In the PPS, unconditioned response at calcium concentrations of 2 and 4 mM, and 15- or 30-ms interpulse intervals of stimulation, no significant differences were found in the latency to induce a 50% amplitude decrease of the CA1 population spikes during hypoxia. On the contrary, in the conditioned response the latency to induce a 50% amplitude decrease of CA1 population spikes was significantly increased (p < 0.01) at 4 mM calcium, 15-ms interpulse interval with respect to experiments with 2 mM calcium, at 15- or 30-ms interpulse intervals. The data indicate that PPI is strongly affected during the early phases of hypoxia and also suggest that drugs increasing PPI could be successfully used for the treatment of brief anoxic or ischemic functional alterations. PMID- 8490736 TI - Origin of laryngeal sensory-evoked potentials (LSEPs) in the cat. AB - Sensory-evoked potentials elicited by electrical stimulation of the superior laryngeal nerve were recorded at the dural surface on the cortex and the caudal medulla in anesthetized cats as a reflection of activities in the central afferent systems. These evoked potentials were named laryngeal sensory evoked potentials (LSEPs). LSEP was mainly composed of five components, N1, N2, N4, N12, and large biphasic potential (LBP). The peak latencies of these components were as follows: N1, 1.09 +/- 0.18 ms; N2, 1.93 +/- 0.19 ms; N4, 3.97 +/- 0.19 ms; and N12, 12.48 +/- 1.01 ms. LBP was a large component lasting from approximately 6 ms to 18 ms. The generator sources of these components were identified as follows: N1, nodose ganglion; N2, presynaptic potentials of the nucleus tractus of solitarius (NTS); N4, NTS complex including the postsynaptic potentials; and N12, activities of the frontal part of the orbital gyrus. The LBP was speculated to be generated from certain subcortical structures, such as the amygdala, the thalamus, the hypothalamus, and the basal ganglia. PMID- 8490737 TI - Regional distribution of soluble and membrane-bound aminopeptidase activities in rat brain. AB - Soluble and membrane-bound aminopeptidase activities in 11 regions of the rat brain were assayed using L-Leucine-2-naphthylamide as a substrate. In addition, two metabolic enzymatic activities were compared: lactate dehydrogenase and aspartate aminotransferase. All enzymatic activities showed significant regional differences when the data were analyzed statistically. Soluble aminopeptidase and aspartate aminotransferase activities were significantly lower in cortical than in subcortical areas. Membrane-bound aminopeptidase activity levels were higher in cortical areas. Lactate dehydrogenase activities did not differ between cortical areas and the rest of the zones studied. However, although no wide regional differences were found for the other enzymatic activities, membrane bound aminopeptidase varied markedly across brain regions: a fivefold difference was observed between zones such as parietotemporal cortex and medulla. The differential distribution of this enzymatic activity is consistent with the hypothesis that it could be responsible for the enzymatic inactivation of some neuroactive peptides. PMID- 8490738 TI - Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression. AB - The effects on locomotor activity (LA) of selective agonists for adenosine receptor subtypes were examined in mice following bilateral injections into the nucleus accumbens (ACB). The ACB is not only richly innervated by dopaminergic (DA) terminals but also exhibits the highest densities of adenosine A2a receptors in the brain. CGS 21680 (2-[p-(2-carboxyethyl)phenethylamino]-5'-N ethylcarboxamidoadenosi ne), a potent and highly selective adenosine A2a receptor agonist, elicited pronounced, dose-related reductions in LA (ID50 dosage = 0.0031 nmol/mouse). NECA (5'-N-ethylcarboxamidoadenosine), a mixed adenosine receptor agonist which exhibits high selectivity and potency at striatal A2a receptors, similarly elicited dose-related reductions in LA (ID50 dosage = 0.0023 nmol/mouse). In contrast, intra-ACB injections of CPA (N6-cyclopentyladenosine), a highly selective agonist for adenosine A1 receptors, did not exert any significant effects on LA, even at 2.0 nmol/mouse, a dosage at which both CGS 21680 and NECA depressed LA by almost 90% compared to vehicle controls. Further, the pronounced locomotor depression elicited by intra-ACB injections of both CGS 21680 and NECA, at approximately the ID65 dosage, was significantly antagonized by IP pretreatment with DMPX, (3,7-dimethyl-1-propargylxanthine), an adenosine receptor antagonist with selectivity for A2 receptors in the striatum, at a dosage (0.15 micromol/mouse) [corrected] which alone had no significant effect on LA. These observations provide support for the notion that adenosine may selectively modulate DA-mediated mesolimbic behavioral circuits via agonist actions at a population of A2a receptors densely concentrated in the ventral striatum. PMID- 8490739 TI - Vasopressin- and oxytocin-immunoreactive hypothalamic neurones of inbred polydipsic mice. AB - In the late 1950s the inbred polydipsic mice, STR/N, was discovered. The early studies indicated that the extreme polydipsia was not due to a lack of vasopressin but probably due to innate thirst of unknown origin. Because the recent investigation has revealed the presence of some functional abnormality in the brain of the STR/N mouse, we now investigated, using immunohistochemical techniques, distribution of vasopressin (AVP)- and oxytocin (OXT)-containing neurones in the hypothalamus of polydipsic strain of mouse and compared with that of the control. The pattern of distribution of AVP- and OXT-immunoreactive neurones in the paraventricular (PV), supraoptic (SO), and suprachiasmatic nuclei (SCN) of the STR/N polydipsic mouse was similar to that of the control, but the number of AVP-immunoreactive neurones was more numerous in the PVN and SON and less in the SCN in the polydipsic mouse than in the control. In addition, a discrete group of AVP- and OXT-containing neurones that was not clearly seen in the control was discovered in the STR/N. These results implicate that abnormal distribution in the brain AVP and OXT contribute to the mechanism responsible for the polydipsia shown by the strain STR/N. PMID- 8490740 TI - Immunohistochemical and chromatographic identification of peptides derived from proneuropeptide Y in the human frontal cortex. AB - Proneuropeptide Y (proNPY) is posttranslationally processed to NPY(1-36)amide and the C-terminal flanking peptide of NPY (CPON). Antisera directed against the N terminal part of NPY, CPON, or CysNPY(32-36)amide were used to identify peptide fragments processed from proNPY in biopsies of human frontal cortical specimens obtained from patients who underwent surgical treatment of profound cerebral tumors. Gel filtration and radioimmunoassays of human cortical extracts revealed that the NPY immunoreactivity was found only as NPY(1-36)amide, indicating that all NPY is present in an amidated form. In contrast, no intact proNPY was identified. NPY/CPON-immunoreactive neurons were observed to be nonspiny with long axonal processes mostly orientated longitudinally in the direction of the superficial layers. Bundles of immunoreactive fibers in the underlying white matter were orientated toward superficial layers of the neocortex, indicating a subcortical origin of some NPY/CPON nerve fibers. Axonal terminals were distributed throughout the neocortex, with highest numbers observed in layer I. Some fibers penetrated from the superficial layer I into the overlying pial surface. Many fibers were also observed in proximity to intracortical blood vessels, and some of these fibers originated from the cortical neurons, indicating that NPY could play a role as an intracortical autoregulator of the tonus of cerebral arterioles. Together these results indicate that NPY(1-36)amide and CPON are present in intracortical neurons as two independent molecules and that NPY may be involved in synaptic processes and regulation of blood flow in the human brain. PMID- 8490741 TI - The opioid agonist ethylketocyclazocine accentuates epinephrine-induced cardiac arrhythmias in the rat through an action in the brain. AB - The purpose of this study was to determine whether the opioid receptor agonist ethylketocyclazocine (EKC) modulates the development of cardiac arrhythmias by an action within the central nervous system. Catecholamine-induced ventricular arrhythmias were produced in the rat by continuous infusion of epinephrine, at incremental doses, until the development of fatal arrhythmias that were usually ventricular fibrillation. EKC, 1 mg/kg, intravenously (IV) significantly (p < 0.05) accentuated the manifestations of or reduced the threshold for epinephrine induced arrhythmias. The effect of EKC was prevented by the kappa opioid antagonist MR 2266 in a dose-dependent manner. To determine whether the central nervous system is a site of this action of EKC, rats received injection of either EKC or the diluent (control) into the lateral cerebral ventricle (ICV). EKC, 100 and 200 micrograms/kg ICV, significantly (p < 0.05) altered the dose-effect relationship between epinephrine and arrhythmias so that EKC accentuated the development of cardiac arrhythmias. These data indicate that EKC, through an action in the brain, modulates cardiac arrhythmias and suggests a role for opioid receptor agonists, such as EKC, in cardiac arrhythmias and perhaps sudden cardiac death in man. PMID- 8490742 TI - Treadmill running test for evaluating locomotor activity after 6-OHDA lesions and dopaminergic cell grafts in the rat. AB - A treadmill apparatus was used for estimating the recovery of locomotor activity after dopaminergic grafts to rats with unilateral 6-OHDA lesions in the nigrostriatal DAergic pathway. Naive control rats, 6-OHDA lesioned rats, and grafted rats were trained to run on the uphill treadmill for 20 min per day for 7 successive days. Weak electrostimulation (ES), less than 1 mA, was used to force running, i.e., if rats did not run they received ES from the grids fixed behind the treadmill belt. The numbers of ES that the rats received were counted because they reflected the frequency with which the rats failed to meet the treadmill speed. Control rats received 5-10 ES/10 min on the first day but only 0-1 ES after the second day. Lesioned rats and grafted rats received over 100 and 50-100 ES/10 min, respectively, during the first 3 days. Thereafter, lesioned rats still received frequent ES (80-100/10 min), whereas grafted rats received less (20 30/10 min). Results indicate that motor ability in grafted rats may not be ameliorated completely despite the recovery from drug-induced rotations. This treadmill running test was found to be a useful method for quantitative evaluation of motor ability. PMID- 8490743 TI - [Errors in the measurement and interpretation of pulmonary artery pressure values evaluated by the Swan-Ganz method]. AB - The data collected by way of the catheter has for goal to give a better therapeutic treatment and is therefore directly related to the quality of the analysis of the signal. The fidelity of the measurements depend on the performance of the material used and also to other distortions linked to their utilization. In intensive care and in perioperative resuscitation, the interpretation must also take into account the possible interference from physiopathologic mechanisms which are sometimes very complex and can modify results in a number of situations both clinical and therapeutic and in particular when they are accompanied by vascular and respiratory perturbations. PMID- 8490744 TI - [Postoperative respiratory depression following ambulatory anesthesia for abortion. Evolution of the ventilatory response to CO2 following the use of propofol alone or in association with different opioids: comparison with midazolam in the same situation]. AB - Sixty patients, undergoing minor gynaecologic procedures, were prospectively enrolled in this randomized study. They were anaesthetized with either propofol or midazolam supplemented or not with fentanyl or alfentanil. Respiratory depression was evaluated using repeated measurements of ventilatory response to CO2 (Read's method) during the preoperative period until the second postoperative hour. No respiratory depression was observed when propofol was used alone. By contrast, midazolam alone induced a significant respiratory depression during the first postoperative hour. PMID- 8490745 TI - [Practical experience in monitoring the oxygen saturation of central venous blood in pediatric anesthesia-resuscitation]. AB - Venous central oximetry (ScO2) in high-risk pediatric surgical patients (myopathies, congenital diaphragmatic hernia) is an useful guide to treatment. ScO2 was monitored in 15 patients (4 neonates) during and after thoracic interventions or interventions involving manipulation of the liver. Oximetrix ScO2 is not more invasive than a catheter of common stiffness, but the size 4F remains large for neonates. The physiological or pathological signification of its variation has to be deduced from clinical evaluation. Interpretation may be easier during anesthesia and in the absence of sepsis. ScO2 can be used either as a sensitive monitoring with usually an early response, to evaluate judicious treatment, or as an indirect way to evaluate cardiac output if the other factors of the Fick relation can be estimated or measured. PMID- 8490746 TI - [A multifunctional anesthesia device: the K circuit]. AB - A practical versatile anaesthesia device is described. An electrical pump provides room air to carry anaesthetic vapours. O2 can also be added if desired. Energy is supplied either by built-in batteries (12 volts = autonomy 6 hours) or external electric mains (12-30 volts or 220 alternative volts). The optimal recommended anaesthetic circuit is the Modified D Mapleson Circuit for economy in oxygen and anaesthetic vapours (for an adult only 6 l are needed). A non rebreathing circuit can also be used: so draw-over ventilation or the use of an auto-inflating bag are possible when no electric power is available. If mechanically controlled ventilation is necessary, a specific ventilator can be adapted. This apparatus has already been manufactured and is very practical on the battle field or in developing countries. PMID- 8490747 TI - [Autotransfusion and controlled hypotension in the surgical correction of vertebral malformations in the child]. PMID- 8490748 TI - [Difficult intubation]. PMID- 8490749 TI - [Vascular filling and vasopressors: effects on the fetus and the newborn infant]. AB - Epidural analgesia and anaesthesia are more and more commonly used in modern obstetrical anaesthesia practice leading to the frequent use of fluid infusion and vasopressors. Fetal and neonatal effects of these treatments are reviewed here and may be summarized as follows: 1) Prolonged and/or severe maternal arterial hypotension may induce fetal hypoxia and acidosis, especially when fetal status is already compromised (uteroplacental insufficiency). 2) Preventive fluid hydratation with crystalloids associated with left uterine displacement are always useful to avoid maternal hypotension. 3) Dextrose-containing solutions are undesirable for the prevention of treatment of maternal hypotension as they may induce delayed neonatal hypoglycemia. 4) When the parturient is correctly hydrated, the rapid use of intravenous ephedrine is efficient in restoring normal maternal arterial pressure and has no deleterious effect on the fetus and the newborn. Finally, rapid, repetitive and non-invasive monitoring of maternal arterial pressure is the prerequisite to a rapid management of maternal hypotension which is essential to avoid any deleterious effect to the fetus and the neonate. PMID- 8490750 TI - [Anesthesia of a child with a cutaneous mastocytosis]. PMID- 8490751 TI - [A severe complication of parenteral nutrition: acute hyperosmolar coma. Apropos of a pediatric case]. PMID- 8490752 TI - [The institution of deferred autologous transfusion in Saint-Louis (Senegal)]. PMID- 8490753 TI - [Inefficacy of coronary circulation due to propofol. Overdose or individual sensitivity?]. PMID- 8490754 TI - [A historical review of the qualifications of anesthetists in Great Britain]. PMID- 8490755 TI - Benefit and cost of prostate cancer early detection. PMID- 8490756 TI - Detection and treatment of testicular cancer. AB - The survival rate for testicular cancer has undergone a dramatic increase from 10 percent in the 1970s to 90 percent in the 1990s. This increase is due to improvements in clinical practice that have now made testicular cancer one of the most curable solid tumors. This article overviews the detection and treatment of testicular cancer, as well as its histology, epidemiology, and natural history. PMID- 8490757 TI - Immunotherapy of renal cell carcinoma. AB - Immunologic approaches to the therapy of metastatic renal cell carcinoma have provided moderate improvement in response rates for a disease that is extremely resistant to all forms of treatment. This article reviews recent clinical efforts using immunotherapy for renal cell carcinoma, including the adoptive transfer of cytotoxic killer cells and/or the use of biologic response modifiers, such as interferon and interleukin-2. PMID- 8490758 TI - Correction in ovarian cancer article. PMID- 8490759 TI - Pathophysiology and treatment of circulatory shock. AB - Circulatory shock is a syndrome characterized by imbalance between oxygen supply and demand. Myriad different mediators are responsible for the systemic manifestations of shock. The therapeutic approach requires initial interventions directed at increasing oxygen delivery followed by definitive therapy for the causative process. Areas of ongoing research involve mediated-directed therapy, reperfusion injury, and immunologic interventions directed at reducing infectious complications in the survivors of circulatory shock. PMID- 8490760 TI - Mechanisms and management of cardiogenic shock. AB - Cardiogenic shock remains the most dreaded complication of acute myocardial infarction. Mortality rates remain high despite modern interventional therapy. Patients with a variety of other cardiovascular entities may also develop cardiogenic shock. Management consists of rapid stabilization of systemic arterial blood pressure, expeditious diagnostic evaluation, and definitive therapy when possible. New therapeutic modalities will be needed if patients with cardiogenic shock are to survive. PMID- 8490762 TI - Hypovolemic shock. AB - This article defines a rational approach to the treatment of hemorrhagic shock. All patients that are hypovolemic following hemorrhage require fluid resuscitation. Some patients require red cell restoration and very few require correction of any clotting deficiencies. A physiologic approach to these problems will lead to optimal patient care in these circumstances. PMID- 8490761 TI - Mechanisms and management of septic shock. AB - Septic shock continues to be associated with high mortality. The systemic effects of severe infections are related to the release and activation of a myriad of mediator systems, central to which are bacterial toxins and cytokines. Therapy includes three facets--resuscitation, treatment of the underlying infection, and interventions directed at ameliorating mediator activity. PMID- 8490763 TI - Secondary organ dysfunction. From clinical perspectives to molecular mediators. AB - The systemic inflammatory response and progression to secondary organ dysfunction are manifestations of the host's responses to injury. This article outlines the clinical manifestations of this injury-response cascade. The potential roles of cytokines, eicosanoids, platelet-activating factor, nitric oxide, oxygen-free radicals, and the leukocyte-endothelial interaction are explored in some detail. A goal-directed therapy of source control, resuscitation, and metabolic support is reviewed, and new therapies with monoclonal antibodies and immunomodulated nutrition are described. These new therapies hold great potential for finally improving the outcome of this fatal syndrome. PMID- 8490764 TI - Assessing perfusion failure during circulatory shock. AB - In patients with circulatory shock, monitoring of tissue perfusion requires assessment of systemic oxygen metabolism. The presence of lactic acidosis helps identify critical hypoperfusion as marked by anaerobic metabolism. Mixed venous oxygen tension and saturation help determine the use of compensatory mechanisms to maintain oxidative metabolism. Measurements of systemic oxygen consumption and oxygen delivery help define underlying pathophysiology and the direction for therapeutic intervention. Tonometrically measured gastric intramucosal pH appears to be a useful method for monitoring splanchnic hypoperfusion and may have implications for assessing global perfusion failure. PMID- 8490765 TI - Fluid resuscitation in circulatory shock. AB - Over the past century, the treatment of various forms of circulatory shock has included fluid resuscitation with either crystalloidal or colloidal solutions. Despite decades of investigation, there still is considerable controversy over the beneficial and adverse effects of each fluid type. Most authors agree that the initial resuscitation of any form of shock should be performed with crystalloid solutions. Trauma resuscitation uses crystalloid therapy almost exclusively. Much controversy exists when the shock state involves increased microvascular permeability, such as seen in sepsis, anaphylaxis, and burns. Concerns involve increased permeability pulmonary edema and whether colloid or crystalloid therapy may contribute to its formation. Regardless of fluid type used for resuscitative efforts, it is essential to ensure adequate invasive and noninvasive monitoring to guide therapy. Endpoints to resuscitation should include stabilization of vital signs, adequate urine output, adequate cardiac output, and evidence of supply-independent oxygen consumption. Side effects of aggressive fluid loading are frequent and include intravascular volume overload, pulmonary edema, increased myocardial water content, brain swelling, gastrointestinal ischemia, and massive systemic edema. These complications can best be minimized by careful fluid titration, using physiologic and hemodynamic endpoints. PMID- 8490766 TI - Pharmacologic cardiovascular support. AB - The availability of newer and better inotropic agents has led to their widespread application in critically ill medical and surgical patients. Although the elective use of inotropic drugs has been associated with adverse outcomes in patients with cardiomyopathy and chronic heart failure, inotropic drugs used as part of treatment protocols designed to optimize oxygen delivery to tissues have been shown to improve outcome in critical illness. Future research must be aimed toward better definition of clinical settings in which outcome can be improved with inotropes and toward identifying safer agents with fewer adverse side effects. PMID- 8490767 TI - Metabolic and nutritional support of the intensive care patient. Ascending the learning curve. AB - The learning curve of nutritional support in the critically ill began with the amelioration of the effects of starvation in patients with a disabled intestine. Next, there was an appreciation that feeding formulas could be tailored to support patients with specific organ insufficiencies. Then it was realized that feeding enterally has distinct advantages over feeding parenterally. In addition to a decrease in catheter-related sepsis, there was noted a distinct decrease in "remote site" sepsis. In fact, good scientific reasons have been identified to explain why this occurs, such as maintaining the competency of the intestine against a translocation of endotoxin and bacteria and "turn-on" of the stress response. Further, we now know that specific nutrients can produce desirable pharmacologic effects. In the future, feeding formulae will be devised that continue to modify the patient's response to illness favorably. Another important consideration is to begin nutritional support as soon as possible--i.e., on the day of admission, if appropriate. The critical care specialist should be expert in these techniques, with the goal of eliminating malnutrition as a confounding variable in the clinical course of the intensive care unit patient. PMID- 8490768 TI - Mechanical ventilatory support in circulatory shock. AB - Mechanical support of ventilation is associated with a number of hemodynamic consequences that result from direct and indirect hydrostatic phenomena, humoral effects, and changes in distribution of peripheral blood flow, particularly in patients with circulatory shock. Each of these is discussed in detail, and recommendations are made for harnessing these effects in order to improve circulation. PMID- 8490769 TI - [New technological equipments and their economical impact in ambulatory care]. AB - The 1st Part of the study, based on 3 opinion surveys among ambulatory care providers (French physicians in private practice) shows a steady increase of prescribed technological "acts". However, the number of physicians having high tech devices in their office is much lower. Ownership is understandably less frequent than equipment leasing or renting. In the French context, turnover of physicians for using high-tech equipment is outpaced by turnover of patients: as a rule, general practitioners send their patients to the specialist's offices or to hospitals (in France, the specialists practice both in ambulatory and institutional settings). The 2nd Part of the study, based on 4,471 physicians' tax files, attempts to identify the investment behavior of doctors in private practice regarding new technological devices. The specialty and the obsolescence speed of the equipment play both an important role. However, the choice between renting/leasing and purchasing depends also whether the doctor has a long run or a short term perspective. Such a choice is clearly evidenced through the French mechanisms of income taxation. It explains why the doctor's annual income (gross or net) is not significantly related to his investment behavior. PMID- 8490770 TI - Acute viral hepatitis in the elderly. AB - Seventy-six cases of acute viral hepatitis in the elderly (65 years old or older) were reviewed. Their clinical symptoms, biochemical pictures and clinical courses were compared with patients less than 40 years old (young) and those 40-64 years old (middle-aged). There were 51 men and 25 women with the mean age of 69 years (range 65 to 78 years). The most common etiology of acute viral hepatitis in the elderly is acute non-A, non-B hepatitis (48.7%), followed by acute hepatitis in HBsAg carrier (44.7%) and acute type B hepatitis (7.9%). Acute hepatitis in HBsAg carrier is the most common etiology in the young and middle-aged patients. Gastric flu, deep or tea colored urine and fatigue-weakness are the common clinical presentations. In conventional liver function tests, serum levels of GPT and albumin tended to be lower in the elderly patients. Overall, 25% of acute viral hepatitis in the elderly were complicated with fulminant hepatic failure or subacute hepatic failure and 18.4% died. The prevalence of fulminant or subacute hepatic failure and the mortality in the elderly were significantly higher than those in the younger patients. PMID- 8490771 TI - Extrapulmonary tuberculosis in children. AB - Extrapulmonary tuberculosis is not a rare infection of children in Taiwan. From 1985 to 1989, we studied 39 children with the diagnosis of extrapulmonary tuberculosis from a total of 43 sites. They were diagnosed by routine diagnostic tests including bacteriologic cultures in 11, pathological features in 25, and clinical presentations in 2 patients. Positive mycobacterial DNA probe method was obtained from a patient with tuberculous meningitis. The most common sites of involvement were lymph nodes in 9 (20.9%), meninges in 7 (16.3%), bone in 7 (16.3%), joint in 6 (14.0%) and miliary infection in 6 (14.0%). The median age of the 2 patients with renal tuberculosis was 14.5 years, which was older compared to the patients with other organ systems involvement. Tuberculin skin tests were significantly positive (> 10 mm) in 54% of the tested children. Among the treated patients, 76% were cured after 9 to 12 months of antituberculous chemotherapy without sequelae, while 24% had sequelae associated with tuberculous infection despite treatment. There was no death reported during the study period. We conclude that extrapulmonary tuberculosis remains an important health problem to the pediatric population of this island despite the overall decline in the incidence of tuberculosis. Early detection and thorough treatment for a suitable period are mandatory to improve the prognosis of this potentially curable infectious disease. PMID- 8490772 TI - Repository dexamethasone in the treatment of acute bronchial asthma. AB - Fifty-two patients with acute asthma requiring immediate therapy but not hospitalization were studied in an emergency department following conventional therapy with bronchodilators. After discharge, the patients were treated with a controlled regimen of long-acting theophylline and beta-agonist inhalation as necessary. They were randomly assigned to one of three groups using a double blind model. Group A received intramuscular and oral placebos. Group B received intramuscular dexamethasone injection along with oral placebo treatment. Group C received oral dexamethasone by a tapering schedule associated with placebo intramuscular injection. Follow-up was carried out 7 days after the treatment in the emergency room. There were no significant statistical differences in the relapse rate among the three groups. Those patients who received oral or intramuscular dexamethasone had a decrease in the need for beta-agonist inhalation and fewer respiratory symptoms. However, there was no significant statistical difference between groups B and C. It was concluded that repository steroids could reduce the respiratory symptoms and frequency of beta-agonist usage as effectively as oral steroid treatment. However, the steroids do not improve the relapse rate in patients with only mild symptoms. PMID- 8490773 TI - Problems of suicide risk management in the emergency department without fixed, full-time emergency physician. AB - Attempted suicide is an often neglected emergency care problem in Taiwan. Using rotating subspecialty residents on emergency room duty and providing them with "Suicide Risk Assessment" sheets and clear disposition criteria, we wished to see if we could improve patient management while at the same time compiling demographic data. From December 1990 to May 1991 we prospectively collected 96 cases. The majority were female, ages 19-40. Twelve patients died, with agricultural poisonings the major cause. The SAD PERSONS scale consistently underestimated the suicide risk, and disposition plans were rarely followed. Only 20% of low risk patients were seen by social service. In the intermediate risk group 64% were discharged despite meeting admission criteria. In the high risk group 33% were also discharged and only one transferred to a psychiatric facility. Without fixed, full time physicians willing to establish and comply with standards of care, the management is unlikely to improve. Well trained Emergency attendings would be an appropriate solution. PMID- 8490774 TI - Squamous cell carcinoma arising in chronic osteomyelitis--clinical analysis of 7 cases. AB - Retrospectively, we analyzed 7 cases of chronic osteomyelitis complicated with squamous cell carcinoma (SCC), who had been treated consecutively in Chang Gung Memorial Hospital from April 1983 to Jan. 1991. There were 6 males and one female, with the age between 43 and 80 years (average 57 years). The distribution of these lesions was 5 in the lower legs and 2 in the thighs; one had another hip lesion. The duration of discharging sinus presented before malignant change was from 4.5 years to 50 years (average 30 years). The pathological findings were all well-differentiated squamous cell carcinoma. Amputation was performed in 5 of them. Limb salvage procedure was selectively done in one case. Chemotherapy and regional irradiation without surgery was given in the remaining case. Follow up examination showed that the short term results were satisfactory in all cases. Six cases had at least one year of follow-up; the longest follow-up was 8 years. PMID- 8490775 TI - [Reconstructive microsurgery in the elderly]. AB - Between 1989 and 1990, 20 patients older than 60 years underwent reconstructive microsurgery in our hospital. The procedures consisted of 6 digital replantations in 5 patients and 17 free tissue transfers in 15 patients. The success were 5 out of 6 digital replantations and 16 out of 17 free tissue transfers. This success rate had no significant difference compared with other age groups of our reconstructive microsurgery series. There was no additional complications which might always be considered to encounter with elder patients after prolonged anesthesia. We conclude that with good preoperative work up, careful intraoperative or postoperative care as well as meticulous operative technique, the operative risk remains low and the success rate is comparable to other age groups. PMID- 8490776 TI - [Post cardiopulmonary-bypass neuropsychiatric complications]. AB - A prospective study of 26 patients undergoing cardiac operation requiring cardiopulmonary bypass was undertaken to determine the incidence and etiologic factors leading to post-operative neuro-psychiatric complications. Detailed evaluation of the patients showed the neuro-psychiatric complications after surgery occurred in 8 of the 26 patients (30.77%). If primitive reflexes were included, the cases increased to 10 (38.46%). Delirium was the most common complication, which was noted in 6 cases (23.08%). Other manifestations were Babinshski sign (2 cases), coma and seizure (1 case), and major depressive symptoms (1 case). Factors evaluated were: age, sex, heart disease, disease severity, type of surgery, combined physical illness, duration of anesthesia, duration of surgery, duration of bypass, mean systolic BP during operation, and mean BP during bypass. The following factors tended to be related to the occurrence of neuro-psychiatric complications: 1) duration of bypass, 2) mean BP during bypass, and 3) mean systolic BP during operation. PMID- 8490777 TI - Syncope in nasopharyngeal carcinoma: report of three cases and review of the literature. AB - Syncope is an uncommon symptom in patients with nasopharyngeal carcinoma (NPC). Here we report three cases of NPC with syncope. One had bilateral neck masses, invasion of the skull base, and lower cranial nerve palsies. The other two presented with neck mass only. Repeated episodes of syncope were initially controlled by intravenous atropine followed by radiotherapy and/or chemotherapy. The large primary tumor with parapharyngeal space extension and neck lymph node involvement, the invasion of the skull base and the presence of lower cranial nerve palsies are the three important risk factors for developing syncope. This is probably mainly due to the mass compression of the carotid sinus or the glossopharyngeal nerve invasion. We therefore classified these 3 cases into carotid sinus syncope type, glossopharyngeal neuralgia type and parapharyngeal space lesions type. The prognosis is poor for cases of NPC with syncope because most patients have advanced or recurrent disease, however, atropine and radiotherapy with or without chemotherapy are effective for the symptomatic treatment of syncope from locally advanced NPC. PMID- 8490778 TI - [Successful embolectomy for acute mesenteric artery occlusion]. AB - Although acute mesenteric ischemia causing bowel necrosis, a surgical emergency, has been diagnosed with increasing frequency today, it remains as lethal as it ever was, with a mortality rate of 70% to 80%. The high mortality rate can be attributed to delayed diagnosis and the presence of underlying disease. Earlier and more liberal use of angiography in patients with high suspicion of acute mesenteric ischemia is mandatory. We report here to a patient, presenting with acute abdomen and bloody stools, who was highly suspected to have superior mesenteric arterial occlusion. He received emergent angiography and successful embolectomy without bowel resection and second-look operation. The post-operative course was rather smooth. An aggressive surgical approach must be considered, and the second-look procedure should be used when the bowel viability is questionable at the first operation. Postoperative anticoagulation therapy should be given when indicated. PMID- 8490779 TI - [Oral complications following a herpes zoster infection of trigeminal nerve]. AB - A case of herpes zoster involving the ophthalmic and maxillary divisions of the trigeminal nerve is reported. It presented as a oral herpes zoster infection with prodromal odontalgia and progressed to spontaneous exfoliation and devitalization of teeth and osteonecrosis of the maxilla. The literature is reviewed and the pathophysiology of tooth exfoliation, tooth devitalization and osteonecrosis by V Z viruses are discussed in addition to the management of herpes zoster and post zoster complications. PMID- 8490780 TI - Reverse systolic flow in dilated pulmonary arteries demonstrated by colour Doppler imaging. AB - OBJECTIVE: To compare patterns of reverse systolic flow in pulmonary arteries in children with dilated and normal pulmonary arteries. DESIGN: Retrospective survey. SETTING: Tertiary pediatric cardiology referral centre. PATIENTS AND METHODS: Colour Doppler images were reviewed on 45 children, aged three months to 17 years, with normal or dilated main pulmonary arteries. The patients included were unoperated, and had isolated lesions and good parasternal short axis colour Doppler images of the main pulmonary artery with no significant pulmonary insufficiency. There were 19 patients with idiopathic dilation of the pulmonary artery, seven with moderate sized atrial septal defect, seven with moderate pulmonary valve stenosis, two with pulmonary hypertension and 10 children who were normal. Reverse flow was identified by adjacent red and blue areas without aliasing. RESULTS: Reverse systolic flow extending into early diastole was seen in 27 of the 35 patients and in two of 10 normals (P = 0.003). The main pulmonary artery was substantially dilated in the patient group compared with normals. CONCLUSIONS: Significant reverse systolic flow was found in main pulmonary arteries dilated idiopathically, or from pressure or volume overload. Reverse flow may be related to excessive capacitance of the main pulmonary artery in these patients. PMID- 8490781 TI - Early patency in acute myocardial infarction. PMID- 8490782 TI - Expanding indications for thrombolytic therapy in acute myocardial infarction. PMID- 8490783 TI - Thrombolytic therapy in patients where hypotension or cardiogenic shock complicate acute myocardial infarction. PMID- 8490784 TI - Thrombolytic therapy in acute pulmonary embolism. PMID- 8490785 TI - Atherosclerosis: who gets it and how it gets there. PMID- 8490787 TI - Hypertension--a modern approach to treatment. PMID- 8490786 TI - Modification of coronary atherosclerosis. PMID- 8490788 TI - Induction of immunosuppression with rabbit antithymocyte globulin: five-year experience in cardiac transplantation. AB - Perioperative induction of immunosuppressive treatment with rabbit antithymocyte globulin (RATG) and late introduction of cyclosporine was used in a group of 77 patients to prevent early renal dysfunction related to cyclosporine. Peak value in plasma creatinine during hospitalization for transplantation averaged 148 +/- 49 mmol/L in patients treated with RATG compared with 215 +/- 21 mmol/L in 39 patients initially treated without RATG induction (P = 0.01). Of patients treated with RATG, 65 +/- 6% remained free from acute rejection at six months versus 40 +/- 8% of untreated patients (P = 0.03). Rates of freedom from infection, from allograft coronary artery disease and from cancer are similar in both groups. Actuarial survival rates were identical in the two groups. The total number of lymphocytes, the percentage of T lymphocytes and of helper T cells were significantly lower when RATG was used. In conclusion, RATG prophylaxis given immediately after transplantation was well tolerated without complication and resulted in adequate immunosuppression to allow delayed introduction of maintenance treatment with cyclosporine. PMID- 8490789 TI - Early experience with directional coronary atherectomy: documentation of the learning curve. AB - OBJECTIVE: To evaluate evolving selection criteria and angiographic outcome ('learning curve') for directional coronary atherectomy. SETTING: Tertiary referral, university-based hospital. PATIENTS: Initial 50 subjects undergoing directional coronary atherectomy of de novo left anterior descending stenoses at The Toronto Hospital from July 1990 to April 1991. INTERVENTIONS: Directional coronary atherectomy according to standard interventional techniques, with pre- and post procedure qualitative evaluation and quantitative coronary arteriography (Cardiac Measurement System; Leiden, The Netherlands) to define angiographic outcome. RESULTS: Comparing 'early' (group 1) versus 'late' (group 2) subjects, baseline demographics and clinical parameters were similar. Later subjects demonstrated increased coronary tortuosity (group 1, 1.40 versus group 2, 1.64, P < 0.01) and major side branch involvement within the stenosis (group 1, seven of 25 [28%] versus group 2, 18 of 25 [72%], P < 0.01). Regardless of experience, post procedure residual minimum stenotic diameters were equal (group 1, 2.75 +/- 0.55 versus group 2, 2.49 +/- 0.42 mm) in progressively longer lesions (group 1, 11.4 +/- 4.9 versus group 2, 13.3 +/- 5.5 mm, P < 0.1), with increased symmetry (group 1, 0.60 +/- 0.28 versus group 2, 0.73 +/- 0.19, P < 0.05). Analysis of consecutive pentiles (10 subjects per group) indicated gradual increases in post procedure residual lumen during early experience (the first 30 subjects), with an abrupt deterioration in outcome (fourth pentile), secondary to qualitative changes in coronary anatomy, before a return to satisfactory residual minimum stenotic diameters (fifth pentile). CONCLUSIONS: This study defines a distinct 'learning curve' during the initial 30 patients undergoing directional coronary atherectomy, with subtle changes in case selection, predominantly reflected by qualitative indices (eg, tortuosity, dystrophic calcification), resulting in a transient deterioration in final outcomes (patient 31 to 40). Subsequently, optimal results were re-established after defining appropriate case selection criteria, in conjunction with progressive expertise. PMID- 8490790 TI - A new in vivo assay of the reactions of microencapsulated human tumor cells to chemotherapeutic drugs. AB - A new cell culture modality had already been established in our laboratory. Using this model, living KB and GBM 8401 tumor cells grew and proliferated exponentially in semipermeable microcapsules, implanted in vivo. The culture method was designed as a modality for a predictive anticancer drug sensitivity test. Its advantages included providing a three-dimensional growth and in vivo supply of nutrients. Tumor cell sensitivity to drugs can be assessed in vivo. The assay is applicable to virtually all histological types of human tumor cells. Using this technique, anticancer drug sensitivity tests of KB and GBM 8401 cells were evaluated. The results showed that such encapsulated cells grew and proliferated rapidly. In addition, the proliferation of KB cells was more rapid than that of GBM 8401 cells under conventional monolayer and in vivo microcapsule culture states. They were very sensitive to adriamycin and fluorouracil, and relatively resistant to cyclophosphamide while cultured in vitro. The viability percentage of microencapsulated KB cells cultured in vivo for two weeks was around 80-90%, roughly similar to that of the same cells conventionally cultured in vitro. However, the proliferation rates of encapsulated KB and GBM 8401 cells in vivo were significantly inhibited by all the drugs tested, with KB cells inhibited more significantly than GBM 8401. These results also suggest that some anticancer drugs needing to be bioactivated in vivo had better test results by this technique, and thus false negative results could be excluded. Also, the good repair capacity of microcapsules implanted in vivo, for damaged tumor cells previously incubated with chemotherapeutic drugs, appears to provide a much better environment for cell growth because much essential nourishment can be supplied. The inhibition percentage of fluorouracil to encapsulated cancer cells from patients with adenocarcinoma of the colon was also tested; they were 69.8% in vivo and 76.5% in vitro. This fast, relatively inexpensive in vivo model can be used to screen various anticancer drugs and help clinical oncologists to select the most effective agents for individual patients. PMID- 8490791 TI - Mitral regurgitation after double balloon or Inoue balloon mitral valvuloplasty. AB - We performed serial color Doppler echocardiographic studies prospectively before and after double balloon or Inoue balloon mitral valvuloplasty in 44 patients (mean age 45 +/- 13, range 20-74) with pure rheumatic mitral stenosis (by angiography) selected in a case-control manner to compare the incidence and severity of mitral regurgitation. After balloon dilation, mitral valve area increased from 0.9 +/- 0.2 to 1.5 +/- 0.4 cm2 (p < 0.001) in the double balloon group and from 0.9 +/- 0.3 to 1.5 +/- 0.3 cm2 (p < 0.001) in the Inoue balloon group. Twenty-four hours after balloon dilation, 3 patients in the double balloon group and 12 patients in the Inoue balloon group developed moderate to severe mitral regurgitation (p < 0.05). The severity of mitral regurgitation tended to persist or progress during follow-up in both groups, although improvement could also be observed. Two patients with severe mitral regurgitation in the Inoue balloon group underwent mitral valve replacement during follow-up. In conclusion, double balloon and Inoue balloon techniques are both effective in relieving significant mitral stenosis. However, Inoue balloon technique may be associated with slightly higher frequency of mitral regurgitation. PMID- 8490792 TI - The effect of selective drainage positions on oxygen saturation in obese patients after upper abdominal surgery. AB - The obese patients undergoing upper abdominal surgery are at particularly high risk to develop postoperative pulmonary complications, and hypoxemia is one of the most common ones reported. During the initial postoperative period, they are often advised to maintain a semi-sitting position to optimize oxygenation. Although chest physical therapy usually avoids a Trendelenburg position, no published data indicate this position as being able to induce desaturation in obese patients following upper abdominal surgery. We studied fifteen adult obese patients without cardiopulmonary disease undergoing upper abdominal surgery. All patients were tested for 5 minutes during the first 3 postoperative days in each of 3 positions: semi-sitting, bed-flat lateral decubitus, and 15 degrees of Trendelenburg lateral decubitus positions. A statistically significant difference in oxygen saturation related to position was found only on the first postoperative day between semi-sitting and bed-flat lateral decubitus positions. The difference in mean SaO2 value between these 2 positions, however, was only 0.88%; and no significant correlation between the magnitude of obesity and the mean SaO2 difference was found. Although arterial oxygen saturation demonstrated statistically significant daily improvement during the first 3 postoperative days, the mean SaO2 values for any 2 consecutive days differed by less than 0.78%. Thus, in obese patients following upper abdominal surgery, 15 degrees of Trendelenburg lateral decubitus and bed-flat lateral decubitus positions do not induce clinically significant desaturation and can be used if necessary and appropriate. In obese patients with borderline oxygenation, supplemental oxygen used postoperatively can maintain adequate oxygenation and allow aggressive positioning. PMID- 8490793 TI - Primary carcinoma of the gallbladder: a review of 10 years of experience at Tri Service General Hospital. AB - Thirty-two cases of primary carcinoma of the gallbladder proven by surgery and pathological biopsy between January 1982 and June 1991 at the Tri-Service General Hospital, Taipei, were analyzed retrospectively. There were 16 male and 16 female patients with a mean age of 66.1 years. The most common clinical manifestations were right upper quadrant abdominal pain and poor appetite. The most common laboratory finding was an elevation of alkaline phosphatase. The preoperative diagnostic rate of this series was 46.9% (15/32 cases), through use of abdominal sonography, computed tomography, endoscopic retrograde cholangiopancreatography and celiac angiography. The coexisting gallstone incidence was 65.6% and the resectability rate, 59.4%. The histological classifications were adenocarcinoma with variable differentiation in 31 cases, and undifferentiated adenocarcinoma in one. The liver was the most common site for metastasis (53.1%), followed by lymph nodes at porta hepatis (21.9%), omentum (12.5%), peritoneum (9.4%), lung (6.3%), colon (3.1%) and duodenum (3.1%). According to the Nevin's staging system, three patients were in stage I and all survived more than five years. Of the two patients in stage II, one survived longer than five years and the other survived longer than seven months. There were three cases in stage III: one patient died of metastasis eight months postoperatively, while the other two cases lived for seven and nine and a half months respectively. There were 24 cases in stage IV and stage V, all of them died less than six months after diagnosis. Poor prognosis for patients with primary carcinoma of the gallbladder makes early diagnosis and treatment important. PMID- 8490794 TI - [Evaluation of radiation doses in mammography]. AB - A dedicated X-ray mammography was introduced to our hospital from 1987 and an imaging receptor of xeroradiography was applied. We reported previously that the average air exposure was 0.79R and that the absorption dose of skin was 1.00 rad. These data are similar to literature reports. Screen-film mammography was introduced recently. To select the best breast imaging and the least radiation exposure, diverse methods were investigated. A dosimetry (Capintec model 192) and a PS-033 parallel ionization chamber were applied to compare the absorption dose on polystyrene phantom between various exposure factors, the application of breast clamp and the size of exposure field. Retrospective estimation of the radiation dose was obtained from the exposure factors of previous mammography since July, 1990 to May, 1992. There were 1035 xeromammographic examinations and 358 examinations with medium-speed screen-film mammography. Another 61 craniocaudal and 96 mediolateral projections with high-speed screen-film mammography were recruited during the recent two months. An ionization chamber (Exradin, Shonka-Wyckoff A5) with an electrometer (Keithley 617) wer selected to obtain the dose equivalent from air exposure between selected exposure factors. The radiation dose of mammography is linearly correlated with voltage/kV and current/mAs. The application of a breast clump reduces 10% of the skin dose. The average exposure factors of xeromammography are 45.6 kV, 163.5 mAs. These results remain the same as in our previous report. Xeromammography has a greater exposure to air, estimated average glandular dose and absorbed dose than screen-film mammography. The mean exposure factor of rapid screen-film mammography gains half the value of medium screen-film mammography, ie. 26.6 kV, 87.0 mAs vs. 26.0 kV, 164.5 mAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490795 TI - [The evaluation of blood perfusion of lower extremities in patients with NIDDM by 133Xe muscle clearance test: a preliminary report]. AB - In this study, we collected twenty NIDDM patients with impaired sensation and clinically suspected angiopathy over both lower extremities. All the patients underwent testing by means of the ultrasonic Doppler technique and were separated into two groups, group 1 with impaired blood flow, and group 2 with no significant impairment of blood flow. Ten normal persons were also included in this study (group 3). The results of the 133Xe muscle clearance test showed that the Q value of group 1 was 0.85 +/- 0.24 [mean +/- SE, ml (100g tissue min-1)], 1.05 +/- 0.31 in group 2 and 1.78 +/- 0.23 in group 3 of normal controls. After statistical analysis, there were significant differences in groups 1 and 2 relative to group 3 (p < 0.05), respectively. This preliminary result indicates that the 133Xe muscle clearance test may be an effective and convenient method to evaluate angiopathy of lower extremities in patients with NIDDM. PMID- 8490796 TI - [Vertical partial laryngectomy and its reconstruction methods]. AB - In the past ten years, we performed vertical partial laryngectomy in 25 patients with glottic carcinomas. These included two T1 cases, seven T2 cases, six T3 cases, and ten post-irradiation recurrent cases. Three types of reconstructive surgery were performed in 24 patients which included 14 patients reconstructed by superior based sternohyoid muscle flap covered with A-E fold or free oral mucosa flap, 7 patients by epiglottic flap, and 3 patients by free fat graft. Most patients healed well post-operatively. Only two post-irradiated patients suffered from fistula due to poor healing, one of whom was found necrosis of sternohyoid muscle flap. In three of those reconstructed by sternohyoid flap, more granulation tissues were noted in the glottis. Transient aspiration was noted in all those reconstructed by epiglottic flaps and some of those by sternohyoid muscle flaps. Later, however, all patients get satisfied with phonation post operatively. Seventeen patients were followed over year and one T3 patients suffered from recurrence six months after surgery. We concluded that superior based sternohyoid muscle flap covered with free oral mucosa for reconstruction of glottis after ventrical partial laryngectomy was a safe and effective method except for post-irradiated patient. Reconstruction with epiglottic flap might be better for such post-irradiated patients. More satisfactory reconstructive method still deserves further investigation. PMID- 8490797 TI - [Follow-up study on screening positives of hypertension and diabetes--results of follow-up by the Yang-Ming Crusade in 1990]. AB - This study was to follow-up the screening positives of hypertension and diabetes screened in 1989 by the Yang-Ming Crusade. The purposes were to understand the control situation of hypertensive and diabetic positives, to understand the continuing situation of diagnosis and treatment by local health center, and to understand the medical attitude and behavior of the screening positives. A total of 768 positives were screened in 1989 and 462 (60.2%) were interviewed. Among them, 44.4% were male and 55.6% were female; 27.7% were aged 50-59 and 28.4% were aged 60-69; 337 positives were hypertensive, 97 were diabetic and 28 had both conditions. The results of follow-up in 1990 showed that, 34.2% of 462 interviewees had gone to the local health center for testing, 37.7% had regular treatment and 19.7% (91 persons) had become normal. The leading methods of treatment were western doctor (35%), local health center (27.2%) and pharmacies (18.7%). Most patients pursued a regular treatment. The reasons not to have a regular treatment were that it was unnecessary because of lack of symptoms (37.2%), lack of time (18.1%), and that it was unnecessary because of cure (3.5%). The results showed that patients lacked knowledge of chronic diseases. Health education is important to let patients have proper information about regular treatment. Logistic regression analysis showed that two factors, "age" and "geographic area", were significantly related to submitting to testing in the local health center. The results of logistic regression also indicated that three factors, "whether having submitting to testing in the local health center or not", "age", and "geographic area", were significantly related to regular treatment. PMID- 8490798 TI - [Stevens-Johnson syndrome: a review of 42 cases]. AB - We retrospectively studied 42 patients hospitalized for Stevens-Johnson syndrome at the Veterans General Hospital-Taipei between 1979 and 1991. Twenty-seven patients were males and 15 females; the ages ranged from 7 months to 82 years old with a mean age 50. The most common precipitating factor was drugs among which diphenylhydantion was the leading offender followed by nonsteroidal anti inflammatory agents and allopurinol. Sixteen cases might be etiologically associated with infection, including 13 with upper respiratory infection, one with acute hepatitis B, one with pulmonary tuberculosis, and one with fever of unknown origin that was suspected to be viral infection. Although mycoplasma infection was thought in the literature to be a common etiologic factor of Stevens-Johnson syndrome, it was scarcely found in our study. Four patients were not treated with systemic steroids but still recovered uneventfully. Systemic steroid as a whole was not proved to be necessary, but early large-dose steroid therapy might abbreviate the course of the disease. The mortality rate was 11.9% which differs unremarkably from the reported rate (5-15%). Two patients died of pneumonia with sepsis, one of hemorrhagic shock (bleeding of adenocarcinoma of stomach), one of aspiration pneumonia, and one of sepsis with disseminated intravascular coagulation, upper gastrointestinal bleeding, and hyperglycemic hyperosmolar nonketotic coma. PMID- 8490799 TI - Primary malignant lymphoma of the breast: report of two cases with literature review. AB - We report two cases of malignant lymphoma of the breast. Extensive investigation on both, demonstrated only a neoplastic lesion confined within the breast. One was managed by local excision, systemic chemotherapy and adjuvant radiotherapy; the other was managed by a modified radical mastectomy, adjuvant radiotherapy and therapeutic chemotherapy. Both of them achieved complete remission 3 years and 1.5 years respectively after management. PMID- 8490800 TI - Pulmonary carcinosarcoma: diagnostic approach by fine needle aspiration biopsy. AB - Carcinosarcoma of the lung is an exceedingly uncommon malignancy, possessing both malignant epithelial and mesenchymal elements. There are less than 100 cases reported in the English literature to date. Most of them were diagnosed by autopsy and surgery. Now we present a detailed report of a case with peripheral variant carcinosarcoma diagnosed by percutaneous needle biopsy under sonographic guidance. The clinical, pathologic and immunohistochemical hallmarks of this unique tumor are also reviewed. PMID- 8490801 TI - Spontaneous rupture of splenic hemangioma: a case report. AB - Splenic hemangioma is rare. The major problem concerning splenic hemangioma is the difficulty of preoperative diagnosis. No characteristic signs allow the specific diagnosis of this tumor. Spontaneous rupture is the main complication, occurring in up to 25% of cases reported. In cases of rupture of the tumor, splenectomy is a life-saving and mandatory procedure. A case of spontaneous rupture of splenic cavernous hemangioma is presented and the literature is reviewed. PMID- 8490802 TI - [Sezary syndrome]. AB - Sezary syndrome is a form of leukemia-lymphoma characterized clinically by erythroderma, pruritus, adenopathy, and circulating atypical cells with cerebriform nuclei. Histologically, atypical lymphocytes in the dermis and Pautrier's microabscesses are often present in skin biopsy specimens. We herein report a typical case of Sezary syndrome showing T-suppressor-cell characteristics, and related literatures are reviewed. PMID- 8490803 TI - Evaluation of the interaction of mu and kappa opioid agonists on locomotor behavior in the horse. AB - This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist. PMID- 8490804 TI - Blood volume increase in salt-induced pulmonary hypertension, heart failure and ascites in broiler and White Leghorn chickens. AB - In this study we tested the hypothesis that excess dietary salt produces an expansion of extracellular fluid volume which may be associated with pulmonary hypertension-induced right ventricular failure in chickens with rapid growth rates. One-week-old broiler and White Leghorn chickens were given 0.5% salt in their drinking water for three weeks. Saline water had a minimal effect on White Leghorns. The hypothesis appears to be correct since salt-treatment in broilers resulted in up to 30% expansion in blood volume and there was 50% mortality from pulmonary hypertension-induced right ventricular failure and ascites. There was marked (up to 88% in some broilers) right ventricular hypertrophy, an indicator of pulmonary hypertension. There was less left ventricular hypertrophy as shown by an increase in the ratio of the right to total ventricle weight. There was up to 32% decrease in growth rate. There was renal hypertrophy in the salt-treated birds as shown by a higher kidney to body weight ratio. PMID- 8490805 TI - Fluorometric measurement of IgG antibody responses in cattle vaccinated with Tritrichomonas foetus. AB - A photometrically-measured indirect fluorescent antibody (IFA) test was developed to measure antibody levels in three heifers vaccinated intramuscularly with two injections (two-week interval) of a vaccine containing formalin-killed Tritrichomonas foetus in oil adjuvant; a separate animal served as a nonvaccinated control. Sera were collected weekly and tested for specific IgG against T. foetus. Antibodies were detectable within two weeks of the initial injection and reached reciprocal titers as high as 7700 as estimated from previously tested reference sera. Titers peaked at six to eight weeks and remained at relatively high levels for the eleven-week study period. The fluorometric assay was easily developed and economical to perform; in addition, it more accurately estimated IgG levels than standard slide IFA tests. PMID- 8490806 TI - Staphylococcus hyicus virulence in relation to exudative epidermitis in pigs. AB - Staphylococcus hyicus strains with different phage types, plasmid profiles, and antibiotic resistance patterns were isolated from piglets with exudative epidermitis. The strains could be divided into virulent strains, producing exudative epidermitis, and avirulent strains, producing no dermal changes when injected in experimental piglets. The results showed that both virulent and avirulent strains were present simultaneously on diseased piglets. This constitutes a diagnostic problem. Concentrated culture supernatants from nine virulent strains injected in the skin of healthy piglets produced a crusting reaction in all piglets. Acanthosis was observed in the histopathological examination of the crustaceous skin. Concentrated culture supernatants from nine avirulent strains produced no macroscopic or microscopic skin changes. Protein profiles from all virulent strains and seven out of nine avirulent strains showed a high degree of protein band homology. An approximately 30 kDa protein present in all concentrated culture supernatants capable of producing skin changes, could not be detected in samples that did not produce skin changes. No other protein showed a similar association. It is concluded that crusting reaction of piglet skin is a suitable indicator of virulence in S. hyicus in relation to exudative epidermitis, and that virulent strains produce a 30 kDa protein, absent in concentrated culture supernatants from avirulent strains. This 30 kDa protein might be an exfoliative toxin. PMID- 8490807 TI - Dynamics and regulation of bulk milk somatic cell counts. AB - Somatic cell count (SCC) in milk is inversely related to dairy cow productivity and milk quality. In an effort to improve product quality, and indirectly farm productivity, regulatory limits on somatic cell counts have been established by many of the major dairy producing countries. The purpose of this paper was to assess the impact of regulations on bulk milk somatic cell counts in Ontario and to assist producers in meeting regulatory limits through development of prediction models. Through the use of a transfer function model, provincial SCC was found to have dropped by approximately 60,000 as a result of the reduction program. Limits of the regulatory program, seasonality and herd characteristics were found through time series cross-sectional models to have an impact on prediction of SCC at the farm level, but the major influence was historical SCC levels. PMID- 8490808 TI - Epidemiology of Pasteurella multocida in a farrow-to-finish swine herd. AB - Thirty-eight clinical isolates of Pasteurella multocida, recovered from a continuous flow, farrow-to-finish swine herd, were characterized by capsular serotyping and restriction endonuclease analysis (REA) in order to study the epidemiology of P. multocida pneumonia. Twenty-three of the 38 isolates obtained in the study belonged to serotype A. They displayed three REA patterns after digestion with HpaII, of which one designated A-3 represented 70% of the samples. The remaining 15 isolates were serotype D. Four different REA patterns were observed in the type D isolates. The REA type D-1 was most prevalent and accounted for 47% of the serotype D isolates. All serotype A isolates were nontoxigenic, whereas five (33%) of the serotype D isolates were toxigenic. Vertical transmission of P. multocida could not be demonstrated, and was probably not a major route of infection. The results of this study suggest that strains of P. multocida virulent for pigs exist and cause swine pneumonic pasteurellosis in continuous flow herds by horizontal transmission. PMID- 8490809 TI - Prevalence and types of birth defects in Ontario swine determined by mail survey. AB - Preweaning mortality in piglets constitutes a major loss to the swine industry. Congenital defects account for a small but significant proportion of these losses. To implement appropriate strategies to reduce such losses, it is necessary to identify the specific causes and their relative importance. Consequently, a mail survey of swine production in Ontario was carried out to determine the prevalence and types of birth defects. Statistical comparisons of the prevalence of overall defects were made between accurate and estimate records, breeds (cross vs. purebred), size of operation (number of sows) and geographic location. The mean litter size of 11 pigs born per sow was not significantly different for those with accurate versus estimate records, but the difference in the prevalence of defective pigs (live and dead) was significant (accurate 3.1% vs. estimate 4.1%). Splayleg (spraddleleg) was the most common defect. The next four defects for both groups were belly rupture, other rupture, ridglings and other, but not in the same ranking. Purebred and small farm operations (< 25 sows) had a significantly higher prevalence of birth defects for estimated data only. Geographic location had no effect. Further work is required to determine whether recording prevalence of birth defects in Ontario swine will provide a useful monitor of environmental stress. The study provides a baseline for the prevalence and type of defects in Ontario swine. PMID- 8490810 TI - The influence of age and health status on the serum alpha 1-acid glycoprotein level of conventional and specific pathogen-free pigs. AB - Serum alpha-1-acid glycoprotein (alpha 1AG) was measured in 212 Landrace White pigs between birth and finishing age. The alpha 1AG level of healthy pigs five to ten months of age was 338 +/- 79 micrograms/mL, and the upper normal limit in mature swine has been established as 500 micrograms/mL. In both specific pathogen free (SPF) and conventional pigs, the alpha 1AG level within one day of birth was 14,263 +/- 2,393 micrograms/mL, 40 times the normal adult value, but rapidly decreased to 699 +/- 186 micrograms/mL by four weeks of age. In conventional pigs, alpha 1AG began to increase after four weeks, averaged 1,428 micrograms/mL by eight weeks, but gradually decreased to adult levels by 20 weeks of age. In comparison, alpha 1AG of SPF pigs was only 800 micrograms/mL at eight weeks and decreased more rapidly to normal by 16 weeks of age. The conventional pigs had a high incidence of clinical pneumonia and specific antibodies to Actinobacillus pleuropneumoniae and Mycoplasma hyopneumoniae at the age of eight weeks. As the clinical pneumonia disappeared, serum alpha 1AG level also gradually declined. In contrast, SPF pigs had little clinical illness, low alpha 1AG, and little serological evidence of microbial infection. Conventional pigs with nonrespiratory infections, encephalitis, or with hernias had increased alpha 1AG. While the very high alpha 1AG level of the neonatal pig may be due to genetic influences, increases later in life are likely in response to stimuli from its external environment. Monitoring of serum alpha 1AG in several herds aided in the recognition of disease processes and may have potential use in swine herd health management. PMID- 8490811 TI - Clinical and pathological findings in dogs following supralethal total body irradiation with and without infusion of autologous long-term marrow culture cells. AB - We developed a canine model for autologous bone marrow transplantation (AuBMT) with long-term marrow culture (LTMC) cells. Marrow was harvested from nine normal dogs. Harvests from dogs 2-7 were placed into 21 day LTMC. Cells in LTMC from dogs 4-7 were labelled with the neomycin phosphotransferase gene neo. Dogs were given 60Co total body irradiation (TBI) and then infused with LTMC cells: dog 1 received 500 cGy TBI and 2.08 x 10(8)/kg uncultured marrow cells. Dogs 2-7 received 600-800 cGy TBI and 0.07-0.45 x 10(8)/kg LTMC cells. Dogs 8 and 9 received 600 and 800 cGy TBI, respectively, but no infusion of marrow or LTMC cells. For all dogs, profound myelosuppression developed during week 1 and pyrexia developed during week 2. Enrofloxacin was given from one day before TBI until a peripheral neutrophil count > 1.0 x 10(9)/L was achieved, which eliminated Escherichia coli from feces. Dogs 1, 2 and 5-9 also received gentamicin and/or combination beta-lactam antibiotics. Numerous platelet transfusions were needed to control hemorrhages in all dogs except dog 1. Dog 1 achieved neutrophils > 1.0 x 10(9)/L on day 15, while dogs 2 and 5-9 achieved this count on days 33-48. Dogs 3 and 4 died on days 17 and 18, respectively, of beta-hemolytic streptococcal sepsis and hemorrhage, with no evidence of hematopoiesis at necropsy. The marker gene, neo, was documented in lymphoid and myeloid cells of dogs 5-7 up to 21 months post-AuBMT. Our studies indicate that dogs can recover following supralethal TBI and can survive the delayed engraftment associated with AuBMT using LTMC cells, if they receive intensive platelet and antimicrobial therapy. Used prophylactically for such therapy, enrofloxacin achieved selective intestinal decontamination, but did not prevent sepsis when used as the sole antimicrobial agent during myelosuppression. Furthermore, our studies indicate that infused LTMC cells, at the above doses, can contribute to hematopoietic recovery, but are not essential for recovery following TBI, and do not shorten the period of prolonged profound myelosuppression induced by TBI. PMID- 8490812 TI - Use of breath hydrogen measurement to evaluate orocecal transit time in cats before and after treatment for hyperthyroidism. AB - Orocecal transit time was evaluated in 13 cats diagnosed with hyperthyroidism. Transit was determined by measuring the change in breath hydrogen and methane concentrations following oral administration of a nonabsorbable carbohydrate (lactulose). Transit times before and three to four weeks after treatment of the hyperthyroidism with radioactive iodine were compared. There was a significant prolongation of transit time, as determined by a change in hydrogen concentration, following correction of the hyperthyroidism (p = 0.034). Average transit times and standard errors were 27.7 +/- 3.7 minutes before treatment and 56.5 +/- 12.1 minutes after treatment. Methane was not detected in any of the samples. Hyperthyroidism appears to be associated with an accelerated small intestinal transit time in cats. PMID- 8490813 TI - The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe. AB - Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe. PMID- 8490815 TI - Contributions to health: a profile of the National Health Research and Development Program. PMID- 8490814 TI - Comparison of medetomidine and fentanyl-droperidol in dogs: sedation, analgesia, arterial blood gases and lactate levels. AB - Medetomidine and fentanyl-droperidol (Innovar-vet) were assessed over a three hour period in 80 healthy dogs. Following physical examination, electrocardiogram (ECG), arterial blood sample analysis, and dynamometer pressure threshold (analgesia score), the dogs were randomly assigned to one of four treatments: Miv -medetomidine (750 micrograms/M2) administered intravenously (IV), Mim- medetomidine (1000 micrograms/M2) administered intramuscularly (IM), Iiv--Innovar vet IV (0.05 mL/kg) or Iim--Innovar-vet IM (0.1 mL/kg). All assessments were carried out by a single individual unaware of the treatment used. Objective assessments included temperature, heart and respiratory rates, analgesia score, arterial blood gases, acid-base and lactate levels. Subjective evaluation included degree of sedation, response to various clinical procedures, noise responsiveness, posture, and the incidence of side effects. Onset and duration of effect were also recorded. The ECG strips were assessed for arrhythmias. Data was analyzed using a 3-way analysis of variance for continuous variables and a Chi square analysis of frequencies. A p value < or = 0.05 was considered significant. Medetomidine-treated animals had a decreased respiratory rate, longer duration of analgesic effect, increased incidence of bradycardia, vomiting and twitching, were less noise responsive and shivered less throughout the study. An increased incidence of second degree heart block with Miv (15 min), a delayed onset and recovery with Mim and increased lactate levels following Iiv (15 min) were observed. No differences were found in other measurements and good to excellent chemical restraint was produced with all treatments in 65% or more cases. PMID- 8490816 TI - Endogenous DNA damage and breast cancer. PMID- 8490817 TI - Prognostic significance of transforming growth factor-alpha in human esophageal carcinoma. Implication for the autocrine proliferation. AB - BACKGROUND: The authors recently used immunostaining to demonstrate that patients with epidermal growth factor receptor (EGFR) overexpression have poor survival after surgery. However, the clinical significance of transforming growth factor (TGF)-alpha, one of the ligands of EGFR, has not been demonstrated in esophageal carcinoma. METHODS: Immunohistochemical study for TGF-alpha and EGFR was performed on 57 esophageal squamous cell carcinomas using monoclonal antibodies. RESULTS: TGF-alpha expression was positive in 35% of the tumors, and EGFR overexpression, defined as stronger staining in cancer cells than in normal epithelium, was positive in 43% of the tumors, according to the authors' arbitrary criteria. The incidence of TGF-alpha positivity was relatively higher in patients with the EGFR overexpression (EGFR+) than in the patients with non overexpression (EGFR-). The survival rate was significantly lower in patients with TGF-alpha(+) than in those with TGF-alpha(-) (P < 0.01) and in patients with EGFR(+) than in patients with EGFR(-) (P < 0.01), respectively. Considering TGF alpha and EGFR expression simultaneously, the survival rate of the patients with TGF-alpha(+)/EGFR(+) tumors was the lowest of the four subgroups, with statistically significant differences noted. These relationships between the immunoreactivities and survival curves were observed in the analysis within patients with node-positive disease. In addition, a multivariate statistical analysis demonstrated that TGF-alpha was the only significant variable, whereas EGFR and nodal status provided no additional information regarding postoperative survival. CONCLUSION: The results presented suggest that TGF-alpha may act as an autocrine growth factor through hyperproducing EGFR and that its expression and EGFR overexpression may prove useful as a valuable prognostic indicator for patients with esophageal carcinoma. PMID- 8490818 TI - High-grade malignant stricture is predictive of esophageal tumor stage. Risks of endosonographic evaluation. AB - BACKGROUND: Endosonography is very accurate for the preoperative staging of esophageal carcinoma. Approximately 20-38% of patients with esophageal carcinoma present with high-grade malignant strictures that preclude passage of the dedicated echoendoscope. In patients with such strictures, endosonographic staging of esophageal tumors may be performed after aggressive esophageal dilatation. However, aggressive dilatation and passage of the echoendoscope in patients with high-grade malignant strictures is not without risk. A detailed assessment of the tumor stage in patients presenting with high-grade malignant stenoses has not been previously reported to the authors' knowledge. METHODS: Seventy-nine patients with esophageal carcinoma were staged preoperatively using endosonography. The results of preoperative staging were compared with the pathologic stage of the esophagectomy specimen when available or the surgical stage (detection of adjacent organ involvement [Stage T4] or metastatic disease [Stage M1] at the time of surgery). RESULTS: Twenty-one patients (26.6%) presented with high-grade malignant strictures precluding endosonographic examination without prior esophageal dilatation. Nineteen of the 21 patients (91%) with high-grade malignant stricture had Stage III or IV disease by histopathologic examination of the surgical specimen. Five of these 21 patients (24%) sustained an esophageal perforation as a result of either wire-guided dilatation, or as a direct consequence of the endosonographic staging procedure. The discovery of metastatic lymph nodes proximal to the stricture resulted in successful staging (assessment of depth of tumor penetration and lymph node involvement) in only 2 of these 21 patients before esophageal dilatation (incomplete staging). Staging of the proximal aspect of the tumor was obtained in the remaining 19 patients before dilatation; however, the accuracy for such incomplete staging was only 33%. CONCLUSIONS: The majority of patients with esophageal carcinoma presenting with high-grade malignant strictures precluding endoscope passage without prior dilatation have a relatively advanced stage of disease (Stage III or IV) compared with those patients presenting with less severe stenoses. There is a significant risk for esophageal perforation (24%) when patients with high-grade malignant esophageal strictures undergo preoperative staging using endosonography. Patients with high-grade malignant strictures, therefore, present a relative contraindication to endosonography using the dedicated echoendoscope. PMID- 8490819 TI - Is the prognosis for Japanese and German patients with gastric cancer really different? AB - BACKGROUND: Differing survival rates have been reported between patients having undergone surgical intervention for the treatment of gastric carcinoma in Japan and Western industrialized countries. Through the actual availability of the data compiled at a major Japanese medical center (National Cancer Center, Tokyo), it was possible, for the first time, to compare the patients and therapeutic results of a Japanese center (n = 1475) with that of a German center (Department of Surgery, Technical University of Munich, Munich; n = 453). METHODS: The prognostic factors involving both groups were compared. Survival rates were analyzed in univariate and multivariate fashions. RESULTS: Some of the examined prognostic factors, such as sex, histologic type, tumor size, and Borrmann classification, were similarly distributed. Differences in frequency were discovered concerning pathologic tumor (pT), node (pN), and metastasis (pM) categories, localization, and age groups. Univariate analysis showed a 2-year survival rate of 88% for all Japanese patients with gastric cancer compared with 58% for German patients. The 5-year survival rates were 77% and 44%, respectively. The difference in the 2-year and 5-year survival rates for both departments may be related to differences in frequencies of several characteristics. In performing the same analysis in a multivariate fashion for the patient populations at both centers, it became clear that an important prognostic factor was the center itself. The survival curves of patients from Tokyo and Munich with the same prognostic factors demonstrate this difference. These differences, however, were small in comparison with those of univariate analysis. CONCLUSIONS: Using a similar classification of the tumor stage and similar prognostic characteristics, the prognosis for gastric cancer in Japan and Germany may be the same. PMID- 8490820 TI - Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas. AB - The incidence of gastric cancer has declined markedly in Finland during the last 4 decades. To document the changes caused by that in the ratio of the intestinal type (IT) to the diffuse type (DT) of gastric carcinoma we compared the 367 cases diagnosed from southwestern Finland at the Department of Pathology, Turku University, from 1950-1959 and 1076 cases from 1980-1989. IT virtually disappeared in the male and female populations younger than 50 years, and in patients younger than 60 years, DT became more common than IT (P < 0.001). The transitional age, the time at which IT exceeds DT in frequency, shifted by 20 years to older age groups. In patients older than 60 years, IT remained the dominant type, but the ratio of IT to DT (IT:DT) decreased in men from 3.8 to 2.1 (P < 0.05) and in women from 4.4 to 2.1 (P < 0.001). No decrease in the frequency of DT could be demonstrated in the material studied. The disappearance of the male-dominant IT in the younger male population changed the male-to-female ratio of patients reported to the Finnish Cancer Registry. When the ratio IT:DT in Finland was compared with the ratios reported by the authors in data from other continents and by other investigators, regional variations in basal level of IT:DT emerged. This phenomenon seems to be based on the differing genetic susceptibility to DT of various races. The decrease of IT, seen in reports from regions with declining incidence of gastric carcinoma, seems to be connected to a diminished rate of severe chronic gastritis. PMID- 8490821 TI - Vascular invasion by hepatic inflammatory pseudotumor. A clinicopathologic study. AB - BACKGROUND: Unusual lesions composed of fibrous tissue, lymphocytes, histiocytes, and plasma cells, called inflammatory pseudotumors (IPT), are being increasingly recognized in many organs and tissues. A hepatic IPT extending into the inferior vena cava has never been reported before to the authors' knowledge. The patient in this study underwent liver resection with cardiopulmonary bypass and circulatory arrest to excise the IPT. METHODS: The tissue was studied extensively using histologic, immunohistologic, flow cytometric, and gene rearrangement analysis and electron microscopic methods. RESULTS: On gross examination, the large hepatic tumor resembled a malignancy invading the vena cava. Microscopically, a mixture of T-lymphocytes, B-lymphocytes, and plasma cells were scattered throughout the tumor. DNA flow cytometry did not reveal aneuploidy suggestive of neoplasia. Genetic analysis of the immunoglobulin and T-cell receptor genes did not detect evidence of clonal expansion of B-cells or T lymphocytes. CONCLUSIONS: This experience with the vascular invasive and biliary obstructive nature of IPT and the difficulty in diagnosing it before or during surgery underscores the potentially adverse impact of this lesion on patients. The authors believe that an aggressive approach should be taken when evaluating and treating hepatic masses, even though they may later be confirmed as being IPT. PMID- 8490822 TI - Treatment of primary neoplasms of the trachea. The role of radiation therapy. AB - BACKGROUND: Primary tracheal tumors are a rare malignancy. Before 1960, most patients had a biopsy, followed by external orthovoltage irradiation or radon seed implantation. Advances in surgery and in radiation therapy during the past three decades have allowed more patients to undergo definitive treatment. METHODS: Between 1957 and 1988, 22 patients with primary tracheal malignancy were treated with curative intent at The University of Texas M.D. Anderson Cancer Center. Five patients underwent primary surgical resection (Group 1), 5 patients had surgical resection and adjuvant irradiation (Group 2), and 12 patients had primary irradiation (Group 3). RESULTS: Median survival times were 26 months for all patients; 16 months for Group 1; 61 months for Group 2; and 26 months for Group 3. Local control was attained in 1 of 5 patients in Group 1, 4 of 5 patients in Group 2, and 4 of 12 patients in Group 3. Among those treated with primary radiation therapy, local control was attained by three of four patients who received 60 Gy or higher and one of eight patients who received less than 60 Gy. Results of chi-square test (P = 0.03) were statistically significant. Severe complications, including treatment-related deaths, occurred in 2 of 5 patients in Group 1, 2 of 5 patients in Group 2, and 3 of 12 patients in Group 3. CONCLUSION: Radiation therapy has a role in the treatment of patients with tracheal malignancy, either as postoperative adjuvant therapy or as sole therapy for those who refuse surgery or have medically inoperable disease. Alternative methods for increasing the local administration of radiation therapy, such as endotracheal brachytherapy, should be investigated for improvement in local control. PMID- 8490823 TI - Esophagectomy for metastatic carcinoma of the esophagus from lung cancer. AB - A patient with metastatic carcinoma of the esophagus from lung cancer is reported. The patient was a 54-year-old woman who underwent a left lower lobectomy for lung cancer 5 years previously. The authors performed a thoracic esophagectomy, dissection of mediastinal lymph nodes, and reconstruction of the esophagus; the surgery was followed by chemotherapy. Because the histologic pattern of the esophageal tumor was similar to that of lung cancer and mucosal involvement was not seen, the esophageal tumor was interpreted to be a metastasis from lung cancer. The patient is well without recurrence of disease 23 months after operation. This is the first report of a successful esophagectomy for metastatic carcinoma of the esophagus from lung cancer. PMID- 8490824 TI - In situ lung perfusion with cisplatin. An experimental study. AB - BACKGROUND: This research work was planned to evaluate the soundness of in situ lung perfusion as a regional administration modality of chemotherapeutic agents. METHODS: Sixteen pigs were randomly divided into four groups and received cisplatin (2.5 mg/kg) through the pulmonary artery using one of the following techniques: stop-flow (Group 1); stop-flow/out-flow occlusion (Group 2); lung perfusion (Group 3); or lung perfusion with 5 mg/kg of infused drug (Group 4). Serial blood (carotid, pulmonary artery and vein) and tissue samples (lung and mediastinal node), were taken before, at completion of, and 5, 10, 15, 30, 60, 120, 180 and 240 minutes after cisplatin infusion for blood gas and platinum content measurement. Blood circulation was restored to the treated organ (for 60 minutes). The animals were killed, and specimens from lung, thyroid, esophagus, heart, liver, spleen, adrenal glands, kidney, bone marrow, stomach, ileum, colon, psoas muscle, and skin were obtained. Platinum concentrations in plasma, plasma ultrafiltrate (free platinum) urine, and tissues were determined by flameless atomic absorption spectroscopy. Lung damage was evaluated by light and electron microscopic examination. RESULTS: Greater systemic plasma, lower pulmonary plasma, and tissue platinum levels were detected when cisplatin was given using the stop-flow technique with respect to the other administration modalities. No significant difference in regional and systemic platinum exposure was found between Groups 2 and 3. However, lung perfusion resulted in higher mediastinal node and lower bone marrow platinum values. Morphologic alterations and impairment of gas exchanges in the treated lung were not dependent on the applied infusion technique. CONCLUSION: This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases. PMID- 8490825 TI - Modified vincristine, doxorubicin, and dexamethasone regimen in the treatment of resistant or relapsed chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group study. AB - BACKGROUND: Thirty-six patients with relapsing or refractory chronic lymphocytic leukemia were entered into a Phase II study of the Eastern Cooperative Oncology Group. METHODS: A modified VAD regimen was given: a 96-hour infusion of 1.6 mg vincristine and 36 mg/m2 doxorubicin with dexamethasone 40 mg by mouth daily for 4 days every 3 weeks. The treatment was continued until two cycles beyond maximal response, which was evaluated after two and six cycles. RESULTS: Of the 33 evaluable patients, 7 (21%) achieved a partial response (PR), with no complete remissions. One-third of the patients (11 of 33) had progressive disease and 15 of 33 (45%) had stable disease, as defined by the National Cancer Institute Working Group criteria. The median duration of PR was 6.5 months, with a median survival time of 14.8 months. A PR was achieved by 3 of 19 patients (16%) who had received prior vincristine +/- doxorubicin and 4 of 14 patients (28%) who had not received vincristine or doxorubicin. Of the nine patients whose disease was refractory to prior therapy, five (55%) achieved a PR. The neurotoxicity of VAD was reduced by decreasing the frequency of the dexamethasone, but 22 of 36 (61%) patients still became infected. Only on infection (2.8%) was life threatening, and there were no infectious deaths. CONCLUSIONS: Because fludarabine has shown superior responses, VAD should be reserved for patients who do not respond to alkylating agents and fludarabine and in whom alternative treatments are not appropriate. PMID- 8490827 TI - Prognostic factors in metastatic melanoma. AB - BACKGROUND: Each year, 6000 people die in the United States from metastatic melanoma. Further study of factors affecting the prognosis of patients with this disease is needed. METHODS: The authors analyzed response and survival data from 635 patients who had entered three Eastern Cooperative Oncology Group trials for metastatic melanoma. RESULTS: Factors associated with poorer survival after study entry included poor performance status and the presence of symptoms, such as reduced appetite, fever, or nausea/vomiting. Male patients had poor survival, as did patients entering the study less than 1 year after a documented recurrence to study entry. As expected, characteristics of the initial primary disease (treatment and symptoms) had little association with survival after entering the advanced disease protocol. Two summary measures of the extent of metastatic involvement had a strong influence on survival. These were the number of nonbone metastases and the clinician's assessment as to the most significant metastatic site. Patients with the liver as their clinically most significant metastatic site had a poorer prognosis than those otherwise classified, including those with central nervous system metastases. The prognosis also worsened with an increasing number of sites of nonbone metastases, including skin and soft tissue. Tumor response occurred in only 11% of the patients. Patients with poor performance status and those with lung involvement had a significantly lower response rate than did others. Although the frequency of response was low, patients with objective responses survived significantly longer than did the nonresponders (based on an analysis appropriately adjusted for the time of response using a time-dependent proportional-hazards model). CONCLUSIONS: These results provide useful guidelines for the design and analysis of clinical trials in metastatic melanoma. PMID- 8490826 TI - A retrospective comparative study evaluating the results of a single-perfusion versus double-perfusion schedule with melphalan in patients with recurrent melanoma of the lower limb. AB - BACKGROUND: Forty-two patients with measurable recurrent melanoma of the lower limb were treated according to a double-perfusion schedule. METHODS: To assess the advantage of this schedule compared with that of a single-perfusion treatment, a retrospective study was done comparing the 42 patients with 45 patients who had undergone a single-perfusion procedure. Both groups were well balanced with respect to patient and tumor characteristics. For patients treated with a double schedule, the dose of melphalan given in the first perfusion was low (6 mg/l; 1 hour; normothermic conditions) to make it possible to perform a second perfusion (9 mg/l; 1 hour; normothermic conditions) with a planned short interval of 3-4 weeks. In the single-perfusion group, a normothermic perfusion with 10 mg melphalan/l was performed. RESULTS: The toxicity did not differ between the two treatment modalities. The response rate was significantly higher in the double-perfusion group (90% versus 68%; P = 0.007) because of a higher complete remission rate (76% versus 48%; P = 0.006). In both groups, approximately half of the patients with complete remission experienced disease recurrence in the perfused area (50% versus 52%). No significant differences were seen in the two groups in the regional node recurrence rate (33% in the double perfusion group versus 20% in the single-perfusion group), distant recurrence rate (50% in the double-perfusion group versus 58% in the single-perfusion group), and their corresponding recurrence-free intervals. The overall 3-year survival rate was 46% in both groups. CONCLUSION: In the patient groups studied, the double-perfusion schedule shows a better complete remission benefit than does the single-perfusion procedure. No differences are seen in limb, regional node, and distant recurrence rates in the two groups. Thus, additional improvement of the perfusion methodology is warranted. PMID- 8490828 TI - Role of mediastinoscopy in superior vena cava obstruction. AB - BACKGROUND: The role of mediastinoscopy in superior vena cava obstruction (SVCO) is not clearly defined. The authors set out to examine the efficacy and safety of mediastinoscopy in SVCO. METHODS: They reviewed 14 patients referred to one surgical team over an 8-year period (1982-1990) who required mediastinoscopy to establish a histologic diagnosis after other less invasive procedures had not established the diagnosis. RESULTS: Of the 14 patients, 11 had lung cancer, 2 had lymphoma, and 1 had malignant thymoma. Definitive tissue diagnosis was obtained in 13 cases. Mediastinoscopy was unsuccessful in one of the cases because no pathologic tissue could be identified at the time of the procedure. Tissue diagnosis could only be obtained in this patient after mediastinotomy, and a lymphoma was found. There was one complication of mediastinoscopy; one patient had arterial bleeding from the innominate artery that required limited sternotomy to control the bleeding. CONCLUSIONS: The authors believe that mediastinoscopy is a safe and effective technique for establishing a histologic diagnosis in SVCO when less invasive techniques have been unsuccessful. The use of blind radiation therapy cannot be justified on an emergency basis; failure to obtain a histologic diagnosis will result in up to 20% of patients receiving inappropriate radiation therapy, making subsequent tissue diagnosis very difficult. PMID- 8490829 TI - Aberrations of chromosome segment 12q13-15 characterize a subgroup of hemangiopericytomas. AB - BACKGROUND: In later years, several characteristic acquired chromosomal aberrations have been identified in mesenchymal tumors. Many of these aberrations, either alone or with histopathologic and clinical data, are useful in diagnosis. The cytogenetic profile of hemangiopericytomas has been poorly investigated. METHODS: Short-term cultures from four spindle cell tumors were cytogenetically analyzed. RESULTS: Clonal acquired chromosome aberrations were found in three of the four tumors: inv(12) (q14q24) in a malignant hemangiopericytoma, a supernumerary der(3)t(3;12) (p21-23;q13-15) in a benign hemangiopericytoma, and t(6;12;19) (p21;q13;p13) in a spindle cell sarcoma that was histologically a malignant hemangiopericytoma or a synovial sarcoma. The fourth tumor, a malignant hemangiopericytoma, had a normal karyotype. The tumors with inv(12) and t(6;12;19) had subclones with trisomy 5 in addition to the structural changes. CONCLUSIONS: The current findings and the literature data indicate that a subgroup of hemangiopericytomas is characterized by rearrangement of chromosome segment 12q13-15. PMID- 8490830 TI - Extraskeletal telangiectatic osteosarcoma. AB - The first three well-documented cases of pure, extraskeletal telangiectatic osteosarcoma of the soft tissues are presented in this article. The distinctive gross features were a predominance of large, blood-filled spaces, which, on histologic examination, were large blood-filled cavities in association with cyst like walls containing anaplastic spindle cells and definite osteoid production in two of three cases. One of the cases is of additional clinical interest because the teen-aged daughter of the woman patient had died 1 year previously of a high grade intramedullary osteosarcoma of bone. PMID- 8490831 TI - Do alcohol intake and mammographic densities interact in regard to the risk of breast cancer? AB - BACKGROUND: The effect of alcohol intake on mammographic densities and the possible interaction between these two factors in regard to the risk of breast cancer were assessed using information from the Breast Cancer Detection and Demonstration Project. METHODS: Mammograms taken during the first year of screening for patients whose breast cancer was detected in the 5th year of follow up (n = 266) and their matched controls (n = 301) were blindly assessed for the percent of mammographic densities, which were measured by planimetry. RESULTS: Among controls, alcohol intake was weakly, positively associated with the percent of mammographic densities (Spearman rank correlation coefficient, 0.09), although the association may have been the result of chance (P = 0.12). After adjustment for confounding factors, the lifetime alcohol intake did not appear to modify the effect of the percent mammographic densities on the risk of breast cancer (P for the interaction, 0.09). CONCLUSIONS: Longitudinal studies and larger case-control studies should be conducted to assess the relationship between diet and changes in mammographic densities further. PMID- 8490832 TI - Association of expression of blood group-related carbohydrate antigens with prognosis in breast cancer. AB - BACKGROUND: It has been thought that carbohydrate antigens, especially Lewis (Le) blood group antigens, are cancer-related antigens. METHODS: The authors conducted immunohistochemical studies to investigate the expression of seven different types of Le carbohydrate antigens in breast cancer tissue and their usefulness as an indicator of the degree of malignancy and as a prognostic factor. RESULTS: When this expression was compared in the cancerous portion of 300 breast cancers and noncancerous mammary ductal epithelium in each of the patients, reduced expression of type 1 carbohydrate antigens and increased expression of type 2 carbohydrate antigens were found in the cancerous portions. No correlation was detected between the antigen expression and clinicopathologic factors. The prognosis of patients in whom type 2 carbohydrate antigens were increased in the cancerous portion, especially Lex (19.7% of patients) and sialyl Lex-i (20.3% of patients), was poorer than in patients in whom they were not increased (P < 0.01). CONCLUSIONS: The relative expression of type 2 carbohydrate antigens in breast cancer tissue seems capable of serving as a prognostic factor. PMID- 8490833 TI - Lung cancer after radiation therapy for breast cancer. AB - BACKGROUND: Radiation, including radiation therapy (RT) for a variety of conditions, is known to be a lung carcinogen. METHODS: Data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for 1973-1986 were utilized to investigate whether RT for breast cancer affects the risk of subsequent lung cancer. The relative risk was calculated by comparing the incidence rate in patients with irradiated breast cancer with that in those with nonirradiated breast cancer. RESULTS: It was found that the risk of lung cancer overall was increased in women who underwent irradiation compared with those who were not irradiated 10 years after the initial breast cancer diagnosis with a relative risk of 2.0 (95% confidence interval, 1.0-4.3). In addition, the risk of lung cancer was in the ipsilateral lung compared with the contralateral lung for irradiated women. This increase was observed after 10 years for lung cancer overall and for the three major histologic subgroups (small cell, squamous cell, and adenocarcinoma). Specific information on RT doses and treatment plans and cigarette smoking were not available. CONCLUSIONS: It was concluded that RT for breast cancer may increase the risk of lung cancer after a latency period of 10 years. PMID- 8490834 TI - Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells. AB - BACKGROUND: Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. METHODS: M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin peroxidase method. RESULTS: Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. CONCLUSIONS: M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer. PMID- 8490835 TI - Long-term survival with adjuvant whole abdominopelvic irradiation for uterine papillary serous carcinoma. AB - BACKGROUND: The optimum management of uterine papillary serous carcinoma (UPSC), a clinically aggressive histologic variant of endometrial adenocarcinoma, is a controversial issue. METHODS: Ten patients with UPSC were reviewed who received whole abdominopelvic irradiation (WAP) as adjuvant therapy after a staging laparotomy and debulking surgery. RESULTS: Nine patients had clinical Stage I disease; the tumors in eight of them were upstaged based on laparotomy findings. There was greater than a 50% invasion of the myometrium in four of the hysterectomy specimens, and vascular space invasion was noted in seven patients. Peritoneal washings were positive in three of the nine specimens obtained; two others showed atypical cells. Five patients are alive with no evidence of disease at 102-133 months. Four patients are dead, and one patient is alive with disease. All recurrences were observed within 30 months of the initial diagnosis and were more common in the presence of deep myometrial invasion and vascular space involvement. Three of the four patients who died had pleural effusions that did not respond to hormonal and/or chemotherapy. Local irradiation produced long-term control of recurrences in two patients, including one with supraclavicular lymph node metastases who had no evidence of disease 117 months after radiation treatment to the involved nodes. CONCLUSIONS: These findings suggest that WAP be considered as an adjuvant therapy in the management of UPSC. The patients with the greatest benefit were those with early disease by surgical staging with or without positive peritoneal cytologic findings. For patients at high risk for pleural effusions and pulmonary metastasis, additional adjuvant therapy, such as innovative chemotherapy or low-dose lung irradiation, needs to be considered. PMID- 8490836 TI - In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma. AB - BACKGROUND: Cisplatin and its analogue carboplatin have been shown to cause dose dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR-3, 2780, HTB-77, and CRL-1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less than-synergistic effect, as was revealed by an isobologram in the OVCAR-3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum sensitive tumors. METHODS: In a Phase II study, the efficacy, the toxicity profile, and the feasibility of combining both substances were assessed in 20 previously untreated patients with ovarian cancer. The regimen consisted of carboplatin (300 mg/m2) on day 1, followed by cisplatin (100 mg/m2) on day 2 every 4 weeks. RESULTS: A total of 81 cycles were administered (median, 4 cycles; range, 1-6 cycles); four patients experienced complete remission and three experienced clinical partial remissions. Limiting toxicities were thrombocytopenia, leukopenia, and ototoxicity. The mean (+/- standard deviation [SD]) carboplatin and cisplatin dose intensities (DI) reached during the first four cycles of therapy were 58 mg/m2/week (+/- 18 mg/m2/week) and 21 mg/m2/week (+/- 7 mg/m2/week), respectively, which corresponded closely to the projected DI of 75 and 25 mg/m2/week, respectively. Based on the equivalence ratio of 4:1, the DI of carboplatin has been converted into the respective cisplatin DI, resulting in a total DI estimate. The overall DI of 37 mg/m2/week (+/- 14 mg/m2/week) was close to the projected one of 44 mg/m2/week. CONCLUSIONS: Combining cisplatin with carboplatin was found to represent a feasible and efficacious therapeutic strategy for increasing platinum dose intensity. PMID- 8490837 TI - Renal angiomyolipomas and HMB-45 reactivity. AB - BACKGROUND: Renal angiomyolipomas (RAML) are mesenchymal hamartomas composed of varying amounts of blood vessels, smooth muscle, adipose tissue, and supporting connective tissue. Although most of these tumors are easy to recognize, some show unusual histologic features and may pose a diagnostic dilemma. Recent reports indicate that RAML are immunoreactive for HMB-45 antibody, which is directed against a premelanomasome-associated glycoprotein and is thought to be specific for melanocytic differentiation. METHODS: To determine whether HMB-45 reactivity would differentiate RAML from other renal tumors, the authors immunostained 72 primary renal tumors, including 19 angiomyolipomas and 2 retroperitoneal liposarcomas extending into the kidney, with HMB-45 monoclonal antibody. Also, the immunohistochemical profile of 19 renal angiomyolipomas was investigated using a broad panel of immunostains, including cytokeratin (AE1/AE3), epithelial membrane antigen, vimentin, smooth muscle actin (SMA), desmin, muscle-specific actin (MSA), S-100 protein, and neuron-specific enolase (NSE). RESULTS: All tumors except RAML were negative for HMB-45 antibody. HMB-45 immunoreactivity was present in 17 of 19 RAML. Seventeen of 19 were positive for SMA and MSA (HHF 35), 8 for desmin, 17 for vimentin, and 9 for NSE. CONCLUSIONS: Based on this study, it was concluded that, along with SMA and MSA, HMB-45 reactivity is a useful tool to distinguish RAML, especially those with unusual morphological features, from other primary renal neoplasms, including liposarcomas that extend into the kidney. PMID- 8490838 TI - Is it justified to avoid radical cystoprostatectomy in elderly patients with invasive transitional cell carcinoma of the bladder? AB - BACKGROUND: Although radical cystectomy is accepted by most urologists as the treatment of choice for invasive carcinoma of the bladder and age alone is not considered a contraindication for radical surgery, many consider radical major operations to be unsuitable for elderly patients. METHODS: The authors compared the results of radical cystectomy in 42 elderly patients to those in patients 69 years old or younger and to a group of 21 elderly patients, matched by stage of disease and severity of medical problems, who received alternative treatment. RESULTS: The overall operative mortality rate was 6.3% (seven patients). Three (4.3%) postoperative deaths in the younger group and four (9.5%) deaths among elderly patients were recorded. The operative morbidity and mortality did not differ significantly between those two groups (P = 0.1). Among the patients who received alternative therapy, 13 (61.9%) died within the first 6 months, and only 3 survived more than 12 months. Morbidity was encountered in 97% of these patients. CONCLUSIONS: The authors showed that radical cystectomy is a relatively safe procedure for elderly patients. The elderly patient who is thought to be unsuitable for surgery not only is deprived of his right to definite curative therapy but also is exposed to higher morbidity and mortality and worse quality of life than are those who undergo operations. The authors conclude that it is unjustified to avoid radical cystectomy in the elderly population on the basis of age alone. PMID- 8490839 TI - Primary carcinoma of the female urethra. Results of radiation therapy. AB - BACKGROUND: This retrospective study analyzed treatment outcomes, patterns of failure, and complications of treating nonmetastatic primary carcinomas of the female urethra with radiation therapy. METHODS: Ninety-seven women with this uncommon malignancy were treated with radiation therapy at the University of Texas M.D. Anderson Cancer Center between 1955-1989. Eighty-six patients received radiation only after excision or biopsy of their primary lesions: 35 were treated with a combination of external beam irradiation and brachytherapy, 21 with external beam irradiation only, and 30 with brachytherapy only. The cumulative doses ranged from 40-106 Gy (median, 65 Gy). The other 11 women received radiation therapy preoperatively. The median follow-up for surviving patients was 105 months (range, 20-337 months). RESULTS: Five-year, 10-year, and 15-year actuarial survival rates were 41%, 31%, and 22%, respectively. Extension of the primary tumor into adjacent structures, involvement of the entire urethral length, and fixation of the primary lesion were all associated with poorer survival (P < 0.05). The 1-year, 2-year, and 5-year local control rates in 84 evaluable patients who received radiation only were 72%, 65%, and 64%, respectively. Only involvement of the entire urethra predicted poorer local control. Twenty-seven of 55 patients (49%) who achieved local control had complications, including urethral stenosis (n = 11), fistula or necrosis (n = 10), and cystitis and/or hemorrhage (n = 6). The complications were considered mild in 5 patients, moderate in 14, and severe in 8. Higher doses correlated with a greater incidence of complications but not with improved local control. There was a trend of fewer complications in more recent years. CONCLUSIONS: Primary carcinoma of the female urethra is curable with radiation therapy, although the complication rates are significant. Current knowledge of normal tissue tolerance and improved brachytherapy techniques may help minimize the complications. PMID- 8490840 TI - A new method for analyzing the cell kinetics of human brain tumors by double labeling with bromodeoxyuridine in situ and with iododeoxyuridine in vitro. AB - BACKGROUND: Cell kinetics studies performed with immunohistochemical techniques to estimate the S-phase fraction have elucidated the proliferative potential of individual brain tumors. METHODS: The authors developed a new double-labeling method that enables other cell kinetics variables, including the duration of the S-phase (Ts) and the potential doubling time (Tp), to be measured from a single biopsy specimen. Using this method, 100 brain tumors were labeled with bromodeoxyuridine (BUdR) in situ and with iododeoxyuridine in vitro; labeled cells were identified by double staining with immunogold-silver and alkaline phosphatase techniques. RESULTS: Ts was fairly uniform (mean, 9.2 +/- 2.1 hour [+/- standard deviation]); range, 6.0-13.7 hours), but Tp varied from 1 day to more than 2 months. The Tp values correlated closely with the BUdR labeling index (LI), or S-phase fraction, and can be calculated from the equation: Tp = 26.9/LI1.02 (r = 0.98, P < 0.005). CONCLUSIONS: This new method facilitates the quantitation of the proliferative potential of individual brain tumors. The S phase fraction, Ts, and Tp can be calculated from analysis of a single biopsy specimen. This method can be used to estimate the prognosis of individual patients with brain tumors and to select treatment modalities more directly than is possible with single-labeling studies with BUdR. PMID- 8490841 TI - Myxopapillary ependymoma. Results of nucleolar organizing region staining. AB - BACKGROUND: Although myxopapillary ependymomas are generally benign with a tendency for slow growth and local recurrence, they are capable of spread within the nervous system and of extraneural metastasis. Histologic features have not been helpful in determining which patients are at risk for recurrence or dissemination, making management decisions difficult. METHODS: A retrospective review was conducted of 14 cases of myxopapillary ependymoma. The nucleolar organizing region (NOR) staining method was used to determine if this technique was useful in the management of these tumors. RESULTS: Five patients had total resections of encapsulated lesions, four had total resections of adherent tumors, and four had subtotal resections. Twelve received postoperative radiation therapy. With a mean follow-up of 80 months, 12 patients are well and disease free. Two patients have had recurrences after surgery and irradiation, leading to death in one and disability in the other. The mean number of NOR per cell in eight specimens ranged from 0.4-1.64. The patient who died with intracranial spread had the highest number of NOR per cell. CONCLUSIONS: Based on these data and a review of the literature, it is recommended that radiation be delayed until recurrence in tumors that have been totally resected. Local radiation therapy may be indicated in subtotally resected tumors. NOR staining shows promise in predicting the likelihood of spread of tumor. Patients with myxopapillary ependymomas should be followed indefinitely because of the potential for late recurrence, even after aggressive therapy. PMID- 8490842 TI - Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. AB - BACKGROUND: Adrenocortical carcinoma is a rare and aggressive disease with a poor prognosis. Adjuvant mitotane administration has been suggested as a strategy that might improve the outcome of patients with localized disease. METHODS: The authors analyzed the clinical outcome of patients with localized or regional adrenocortical cancer. The study included 19 patients who were registered at M.D. Anderson Cancer Center during a 3-year period and who had localized or regional disease at the time of surgery. Of these, eight patients received mitotane postoperatively and continued the drug until their last contact or recurrence (Group A, adjuvant); five patients began taking mitotane after surgery but discontinued it after 2-12 months for reasons unrelated to the disease (Group P, postoperative); and six patients did not receive mitotane (Group N, no mitotane). All patients have been followed for at least 12 months. RESULTS: The treatment groups differed significantly in their time to recurrence; the disease-free interval was shortest in Group A (P = 0.0055, by log-rank test). There was no statistical difference in survival among the groups, but the profile remained unfavorable for Group A. The 2-year survival rate was 100% for Groups N and P but only 43% for Group A. Of the potentially confounding factors, gender, age, steroid hypersecretion, and tumor size, none had any influence on recurrence or survival rates. CONCLUSIONS: These findings do not support the conclusion that adjuvant mitotane is beneficial in patients with localized or regional adrenocortical cancer. Neither the disease-free interval nor survival was improved by the drug. The authors suggest that alternative therapeutic strategies be explored for the management of these patients. PMID- 8490843 TI - Prognostic significance of clinical and pathologic features in diffuse large B cell lymphoma. AB - BACKGROUND AND METHODS: The diffuse large cell non-Hodgkin lymphomas are a heterogeneous group of neoplasms that are potentially curable. To identify important predictors of clinical outcome, the authors evaluated the clinical and pathologic features of 114 patients with newly diagnosed diffuse large B-cell lymphoma who were uniformly staged and treated with curative intent. The authors were particularly interested in determining whether any pathologic features added to the ability of the clinical features to predict patient survival. RESULTS: Several clinical and pathologic features were found to be associated with survival by univariate analysis. However, multivariate analysis disclosed that only the stage of disease and the symptom status were significantly associated with survival. Low stage and lack of B symptoms were favorable indicators of overall survival and failure-free survival. CONCLUSIONS: The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes. PMID- 8490844 TI - Energy expenditure in dogs with lymphoma fed two specialized diets. AB - BACKGROUND: Cancer-caused cachexia has been reported to be caused in part by an increase in energy expenditure, and diets with nutrient profiles containing 30 50% nonprotein calories as fat instead of carbohydrate may exacerbate this state of inefficient energy utilization. METHODS: Indirect calorimetry was performed on 22 dogs with high-grade lymphoblastic lymphoma that were randomized into a blind study and fed isocaloric amounts of a high-fat diet (Diet A) or a high carbohydrate diet (Diet B) before and after remission was attained with up to five doses of doxorubicin chemotherapy (30 mg/m2 intravenously). Indirect calorimetry was also performed on 30 normal dogs for comparison. RESULTS: During the initial evaluation period, the resting energy expenditure (REE/kg0.75, P < 0.05) and respiratory quotient (RQ, P < 0.05) were significantly lower than in the controls. Six weeks after the start of the study, the REE/kg0.75 and oxygen consumption (VO2/kg0.75) were significantly (P < 0.05) lower in both groups of dogs with lymphoma compared with the controls. The RQ determined 6 weeks after the start of the study for the dogs fed Diet A was significantly (P < 0.05) lower compared with that in the controls evaluated at the same time. When the two groups of dogs with lymphoma were compared with each other, there was no significant difference in any of the outcomes. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group fed Diet A after the third evaluation period compared with the second evaluation. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group given Diet B at the fourth evaluation period compared with the fifth. CONCLUSIONS: These data suggest that energy expenditure of dogs with lymphoma decreases transiently in response to chemotherapy and remission, but these values are less than those determined in normal dogs and not altered significantly by diet. PMID- 8490845 TI - Dose-related cutaneous toxicities with etoposide. AB - BACKGROUND: Cutaneous toxicities are seen frequently in association with administration of high doses, but not standard doses, of agents. With the increasing use of etoposide in dose-intensive regimens, cutaneous toxicities are appearing with increasing frequency. METHODS: A retrospective analysis of 145 patients treated with various doses of etoposide was conducted. RESULTS: This analysis revealed a statistically significant increase in the frequency of these toxicities at doses of 2400 mg/m2 and 4200 mg/m2, compared with doses of 1800 mg/m2. Intense, painful palmar erythema accompanied by bullae formation and desquamation occurred at the 4200 mg/m2 dose. Symptoms were controlled by a short course of corticosteroids. CONCLUSION: Although they are not dose limiting, substantial dose-related skin toxicities can be an important side effect of high dose etoposide therapy. PMID- 8490846 TI - Intravascular lymphomatosis. A systemic disease with neurologic manifestations. AB - BACKGROUND: Intravascular lymphomatosis (IL) is a systemic neoplasm that often involves the nervous system, inducing progressive neurologic deficits in the setting of undiagnosed or quiescent extranodal non-Hodgkin lymphoma. METHODS: The clinical and pathologic files of the Massachusetts General Hospital and New York University Medical Center and the English language literature were reviewed to identify all reports of intravascular lymphomatosis (angioendotheliomatosis) or other examples of a diffuse proliferation of neoplastic cells filling capillaries, arterioles, and venules. RESULTS: The authors report seven patients with IL and note 114 patients reported in the literature. Almost two-thirds (63%) of patients had neurologic manifestations, without abnormalities on bone marrow biopsy, chest and abdominal tomographic examinations for adenopathy, and cerebrospinal fluid (CSF) analysis. All patients had one or more of four syndromes, each reflecting a vascular occlusive process: progressive, multifocal cerebrovascular events; paraparesis, pain, and incontinence; a subacute encephalopathy; and peripheral or cranial neuropathies. CONCLUSIONS: The unexplained presence of any one or more of these neurologic syndromes should alert the physician to the possible presence of this disease. PMID- 8490847 TI - Chemotherapy for pilocytic astrocytomas. AB - BACKGROUND: Although pilocytic astrocytomas (PA) generally are considered benign, a subset of patients with PA have disease progression despite standard treatment with surgery and radiation therapy. The authors report their experience with chemotherapy in this patient group. METHODS: The authors treated 11 patients (4 males and 7 females; median age at diagnosis, 8 years) with pathologically confirmed PA with chemotherapy. In eight patients, tumor progression or recurrence despite prior surgery and radiation therapy led to chemotherapy treatment. In three children younger than 5 years, chemotherapy was given in lieu of radiation therapy immediately after diagnosis (in one patient) or at the time of disease progression after surgery (in two patients). The authors used ten different chemotherapy regimens to treat the 11 patients. RESULTS: Chemotherapy produced clinical and radiographic improvement (R/R) in four (36%) patients, clinical stabilization and radiographic improvement (SD/R) in 1 (9%), clinical and radiographic stabilization (SD/SD) in 3 (27%), and was associated with clinical and radiographic progression (PD/PD) in 3 (27%). Three of the five patients with radiographic improvement had a greater than 75% reduction of maximal cross-sectional tumor area. Hematologic toxicity resulted in dose reductions in 43 of 110 (39%) total courses of chemotherapy. There were three hospitals admissions for fever and neutropenia and one chemotherapy-related death. CONCLUSIONS: The authors conclude that chemotherapy may benefit those with progressive inoperable PA. Chemotherapy may delay the need for radiation therapy in young patients with unresectable PA requiring treatment. PA may be a chemosensitive primary brain tumor. PMID- 8490848 TI - Correlation between morphologic and other prognostic markers of neuroblastoma. A study of histologic grade, DNA index, N-myc gene copy number, and lactic dehydrogenase in patients in the Pediatric Oncology Group. AB - BACKGROUND: Histologic grades (HG), N-myc (NM) gene copy number, DNA index (DI), and serum lactic dehydrogenase (LDH) have been shown to be related to prognosis in neuroblastoma. The relationship between HG and nonmorphologic prognostic markers has not been investigated previously. METHODS: Each prognostic marker was determined independently and without the knowledge of clinical features and outcome by different investigators in 275 (HG), 96 of 275 (DI), 94 of 275 (NM), and 224 of 275 patients (LDH) with neuroblastoma by methods described previously. Patients younger than 2 years of age were included in the analysis for DI. Patients of all ages were included in the analysis of HG, NM, and LDH. RESULTS: A statistically significant association of low HG (1 and 2) was found with DI of more than 1 (hyperdiploid), single copy of NM gene per haploid genome, and an LDH of less than 1500 IU/l (P value for each, < 0.001), factors that are associated with better prognosis. High HG was associated with DI of 1 (diploidy), amplified NM gene, and an LDH of 1500 or more, factors that are associated with aggressive behavior. CONCLUSION: The value of HG is strengthened by its statistically significant association with features that reflect tumor cell biology of neuroblastoma. In view of the tissue sample size required for determination of HG, consideration should be given to obtaining such a sample in as many patients as is feasible if there is no contraindication to surgery. Nonmorphologic prognostic markers, when used in concert with HG, would provide a basis for individualized risk-specific therapy of this disease. PMID- 8490849 TI - General Motors Cancer Research Prizewinners Laureates Lectures. Charles F. Kettering Prize. Clinical trials in testicular cancer. AB - Testicular cancer has become a model for a curable neoplasm. Our studies with cisplatin combination chemotherapy allow us to conclude that (1) short-duration intensive induction therapy with the most active agents in optimal dosage is more important than maintenance therapy; (2) modest dose escalation increases toxicity without improving therapeutic efficacy; (3) it is possible to develop curative salvage therapy for refractory germ cell tumors; and (4) preclinical models predicting synergism, such as vinblastine+bleomycin or cisplatin+VP-16, have clinical relevance. Finally, testicular cancer also has become a model for new drug development. Cisplatin was approved by the FDA for testis and ovarian cancer and VP-16 and ifosfamide for refractory germ cell tumors. The success of these studies confirms the importance of the continued search for new investigational drugs in all solid tumors. PMID- 8490850 TI - General Motors Cancer Research Prizewinners Laureates Lectures. Charles S. Mott Prize. Reproduction and cancer of the breast. PMID- 8490851 TI - Patterns of care. PMID- 8490852 TI - Cancer in adolescents and young adults. PMID- 8490853 TI - Principles of psychosocial programming for children and cancer. PMID- 8490854 TI - Long-term survival. Clinical care, research, and education. PMID- 8490855 TI - Resources for care. PMID- 8490856 TI - Prevention and detection. PMID- 8490857 TI - Laboratory-clinical interface. PMID- 8490858 TI - Trends in patterns of treatment of childhood cancer in Los Angeles County. AB - To assess the proportion of children with cancer who have been managed by mainstream pediatric cancer programs, population-based cancer incidence data for Los Angeles County (LAC) children (under 20 years of age) for the years 1972 through 1987 were linked with patient records of children registered with the two national cooperative pediatric oncology groups, Children's Cancer Study Group and Pediatric Oncology Group. The proportion of children with cancer who were registered by cooperative groups increased markedly over time: 9% of LAC children younger than 15 years of age who were diagnosed with cancer in 1972 were registered with cooperative groups, compared to 52% of those diagnosed in 1980 and 62% of those diagnosed in 1987. Registration rates decreased with increasing age at cancer diagnosis. In the most recent time period, 1984-1987, 66% of LAC children diagnosed with cancer under age 5 years were registered with cooperative groups compared to 62% of those who were 5 to 9 years old and 49% of those who were 10 to 14 years old; although they were frequently diagnosed with tumors considered to be childhood cancers, only 19% of older adolescents (aged 15-19 years) were registered. In LAC, there was no apparent bias in registration rates with regard to gender or racial-ethnic background. Among patients diagnosed in the period 1984-1987, children in the highest of five socioeconomic status categories were underrepresented among registrants. Registration rates were highest (70% or greater) for patients with acute lymphocytic and acute nonlymphocytic leukemia, medulloblastoma, hepatoblastoma, Wilms tumor, and rhabdomyosarcoma. Fewer than 50% of patients with other brain and central nervous system tumors, retinoblastoma, other soft tissue sarcomas, and bone tumors were registered with the cooperative groups. PMID- 8490859 TI - What can be learned about childhood cancer from "Cancer statistics review 1973 1988". AB - BACKGROUND: National data on childhood cancer is becoming more available, but there continues to be a paucity of information. METHODS: The 1991 edition of Cancer Statistics Review was scrutinized for information on the status of pediatric cancers in the United States. RESULTS: The evidence indicates that in the United States, cancer among children younger than 15 years of age is increasing in incidence. In this age group, cancer is increasing equally among whites and blacks and among girls and boys. In white children, the increase appears to be largely due to increases in acute lymphoblastic leukemia and tumors of the brain and nervous system, and not to changes in Wilms tumor, soft tissue and bone sarcomas, lymphomas and Hodgkin disease, or other common malignancies of childhood. The data in the report demonstrate that the cancer mortality rate before age 15 continues to decline steadily in both sexes and both races. Despite an increase in the incidence rate of 4% between 1973-1988, the overall cancer mortality in children younger than 15 years has decreased 38%. CONCLUSIONS: The data may be interpreted to indicate that in the United States, the current cure rate of all childhood cancers combined is between 70-90%. PMID- 8490860 TI - The practice patterns of adult oncologists' care of pediatric oncology patients. AB - The role of the adult oncologists in the area of pediatric cancer treatment previously has been unmeasured. A questionnaire bearing regarding the practice of 447 adult oncologists was administered in June 1991. The membership list of the Association of Community Cancer Centers was used to identify contact oncologists. One hundred thirty-one questionnaires (29.3%) were returned for analysis. The data reveal that 204 patients younger than 21 years of age were treated during the last year in 63 adult oncology practices. Most of these patients were more than 15 years of age. Only a minority (53) were treated in rural practices. In addition, only a minority (27%) of these patients are reported to be enrolled in clinical trials. In addition, adult oncologists appear to regard physiologically mature adolescents (age 16-21 years) as adults. They do not seem to make a distinction between patients 16-21 years old and those older than 21 years. PMID- 8490861 TI - Infrastructure for pediatric intervention trials. PMID- 8490862 TI - National Coalition for Cancer Survivorship perspective. Group V: resources for care. PMID- 8490863 TI - Introduction to psychosocial issues. PMID- 8490864 TI - Psychosocial issues in the world of children with cancer. PMID- 8490865 TI - School issues and the child with cancer. AB - American Cancer Society (ACS)-funded research projects in the 1980s were significant in the development of current school intervention programs for children and adolescents with cancer. These programs need to be part of the psychosocial service of every pediatric hematology/oncology center, not only for those student/patients with highly visible problems but for all children; first, to ensure a smooth re-entry into school after diagnosis; and second, to identify any cognitive and academic dysfunctions that may result from treatment. The restructuring of special education services in the public schools in the United States and decreasing budgets are a challenge to the ACS to join with other health organizations to lobby at the local, state, and national level for services for all children regardless of diagnosis. Classroom teachers need to be empowered by parents and hospital personnel to develop creative, situation specific interventions on behalf of each child and to work with the school psychologist to assess and make appropriate recommendations for students with cognitive late effects. This population needs ongoing support as they progress through the educational system and make transitions from one level of education to the next. PMID- 8490866 TI - Financing care for children with cancer. PMID- 8490867 TI - Issues affecting nursing's support for children with cancer. AB - During the past 17 years, pediatric oncology nursing has evolved from an unknown specialty into an organization exemplary of advanced nursing practice. Pediatric oncology nursing is now recognized as a distinct subspecialty within pediatric nursing. The Association of Pediatric Oncology Nurses (APON), organized in 1976, has grown from an initial 10 members to 1200 members in 1990. The growth of pediatric oncology nursing as a specialty is due largely to a group of nurses responsible for the organization of APON. These individual's vision in the early 1970s shaped the future of pediatric oncology nursing by promoting the development of nursing standards that increased nursing's accountability for the care of children with cancer. Today, nurses play a major role in the complex management of childhood cancer. Issues facing the nursing profession during the next decade will have a direct impact on the specialty of pediatric oncology nursing. The nursing shortage, nursing's changing image, and emerging nursing roles will influence pediatric oncology nursing's ability to care for children with cancer and their families in the future. As pediatric oncology continues to advance, innovative nursing roles must evolve to meet the health care needs of children with cancer. PMID- 8490868 TI - Cancer in adolescents and young adults. Psychosocial concerns, coping strategies, and interventions. AB - Adolescent cancer patients present a unique challenge to health care professionals because of the impact of the disease and its treatment on the successful acquisition of age-appropriate developmental milestones, as well as the psychosocial concerns raised by the illness itself. Understanding normal adolescent development provides a framework for identifying psychosocial concerns, predicting problems, and developing appropriate interventional strategies for adolescents with cancer. A comprehensive support program with specific goals of promoting adjustment to the illness and providing a basis for community reentry by strengthening recognized coping strategies based on identified psychosocial concerns is described as a model. PMID- 8490869 TI - Enhancing child-family-health team communication. PMID- 8490870 TI - Access, insurance, and personpower. AB - This presentation will focus on the issues of access to care, insurance, and personpower in pediatric oncology. The invitation to participate in this workshop was addressed to me as former Chairman of the Section of Hematology/Oncology of the American Academy of Pediatrics and current Chairman of the sub-board of Pediatric Hematology/Oncology of the American Board of Pediatrics. I am particularly indebted to my colleagues in these two organizations for supplying me with much of the information included in this report. PMID- 8490871 TI - Section on resources for care of children with cancer. Human, financial, and institutional requirements. PMID- 8490872 TI - Adult survivors of childhood cancer. Employment and insurance issues in different age groups. AB - Survivors of adult forms of cancer have noted discrimination in obtaining employment appropriate to their abilities/training and in securing comprehensive, affordable health and life insurance. Among survivors of childhood cancer, these problems are complicated, because most survivors of childhood cancer have no employment record and only family-related insurance before the onset of cancer. Relative to these issues, adults who are survivors of childhood cancer can be divided into two groups, i.e., those who are younger and those older than 30 years of age. In the older age group (30-50 years), the general indicators of economic achievement and insurability are similar to those of control subjects. Exceptions in this age group include denial of entry into the uniformed services and rejection of applications for life insurance. Survivors who are 20-29 years of age have a wider range of areas in which there is variance from control subjects, including educational achievement, employment, workplace relationships, and the ability to obtain health and life insurance. PMID- 8490873 TI - Disordered differentiation as a target for novel approaches to the treatment of neuroblastoma. AB - Some childhood malignant neoplasms are thought to arise in embryonic tissues. These tumors present unique opportunities for studying the maturation of specific cellular lineages and examining the possible role of alterations in the regulation of differentiation in tumor development. Several features of neuroblastoma, a tumor thought to arise in cells originating in the embryonic neural crest, suggest that it may be particularly useful in this regard. The identification of a series of markers that characterize the various cell types of the peripheral nervous system that are detectable in neuroblastoma tumor tissues has made it possible to recognize that the cells of neuroblastoma tumor cell lines and tissues correspond to specific stages of adrenal gland development. Experiments directed at understanding the cellular signals by which neural crest cell maturation is mediated may provide insights of therapeutic import because neuroblastoma tumors corresponding to some stages of differentiation respond very differently to nonspecific cytotoxic therapies than tumors corresponding to other stages. PMID- 8490874 TI - Social support and social cognitive problem-solving in children with newly diagnosed cancer. AB - Children newly diagnosed with cancer have been documented to be at increased risk for difficulties in their return to school and ongoing positive social experiences. This article reviews the critical role of social support in helping children adjust to their illness and treatment. Social skills training for newly diagnosed children is presented as an important intervention strategy for increasing positive social interactions and overall psychosocial adjustment. A randomized, clinical research trial currently in progress that will evaluate the impact of social skills training on newly diagnosed children 5-13 years of age is delineated. The potentially positive impact of social skills training on the prevention of emotional problems and increased biologic survival are discussed. PMID- 8490875 TI - Pediatric molecular oncology. Past as prologue to the future. AB - The great successes in the treatment of childhood cancers have been followed in recent years with a new understanding of the molecular genetic abnormalities that underlie their origin. For some cancers these genetic changes are in oncogenes; in others, they are in antioncogenes, or tumor suppressor genes. Initiating aberrations in the former are associated characteristically with chromosomal translocations, the analysis of which should soon lead to the identification of oncogenes other than those in the myc family. Several tumor suppressor genes of importance in the childhood cancers have been cloned and others should soon follow. It is reasonable to expect that during the current decade molecular understanding of the genetic defects in the major pediatric cancers will be achieved. The knowledge gained through these studies, past and future, may provide new approaches to prevention and treatment and lead to additional progress. PMID- 8490876 TI - Patterns of enrollment on cooperative group studies. An analysis of trends from the Los Angeles County Cancer Surveillance Program. AB - To assess the proportion of children diagnosed with cancer who are enrolled on studies conducted by the two national pediatric cooperative groups, population based cancer incidence data for Los Angeles county children younger than age 20 for the years 1980 through 1987 were linked with patient records of children registered with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG). For patients not enrolled on a protocol, demographic and disease characteristics were compared with summary eligibility requirements for CCG protocols that were open for enrollment during 1980-1987. The proportion of patients enrolled on studies conducted by the cooperative groups varied with tumor type and age at diagnosis. When patients younger than the age of 10 were diagnosed at an institution affiliated with one of the groups, the majority of those evaluated by our review as eligible for a study were enrolled on a protocol. The proportion of young patients entered on study among those whose diagnosis was not made at a cooperative group institution was generally smaller. Seventy-three percent of all potentially eligible patients with acute leukemia diagnosed between 1980-1987 were entered on a pediatric group protocol. Approximately 50% of all potentially eligible patients with brain tumors were entered on protocol. In contrast to this, less than 50% of patients older than the age of 14 and likely to be eligible for a study were entered on a pediatric group protocol, regardless of the tumor type. Indeed, bone tumors constituted the category of patients most likely to be enrolled, with 39% of all potentially eligible patients entered on a study in the period examined. If the patient's diagnosis was made at a cooperative group institution, the individual was more likely to be entered on a protocol than if the diagnosis was made at a center outside the cooperative group network. It was not possible to determine the precise reason for this trend from the data available. Some explanations include policies at cooperative group institutions regarding admission of patients older than age 14 and the availability of protocols from cooperative groups primarily focused on the treatment of cancers of adults. PMID- 8490877 TI - Using a population-based registry to identify patterns of care in childhood cancer in Florida. AB - BACKGROUND: Unlike cancers occurring in adults, childhood cancers are distinguished by being primarily nonepithelial in origin and by their relative rarity. Even with the availability of registries such as the Surveillance, Epidemiology and End Results program of the National Cancer Institute or the Florida Cancer Data System for the State of Florida, there are potential biases that may affect the estimates of pediatric cancer incidence, studies related to elucidating patterns of care, and other epidemiologic studies. METHODS: To evaluate the magnitude of these potential biases and elucidate the settings (pediatric cancer center versus non-cancer center) in which childhood cancers are treated, the authors performed a retrospective study of childhood cancer in Florida. RESULTS: Approximately 19% of childhood cancer cases (in patients 0-19 years of age) in Florida diagnosed from 1981 to 1986 were treated outside of identified pediatric cancer centers in the state. Children with Hodgkin disease and brain tumors represented 43% of these cases. Among those cases treated in pediatric cancer centers, 23% were treated by physicians other than pediatric oncologists. Children with brain tumors represented 28% of these cases. Of those treated by pediatric oncologists, 65% were eligible for a cooperative group protocol and 55% of these were enrolled. CONCLUSIONS: Population-based registries are necessary for describing the full extent of childhood cancer, but they have limitations in demonstrating patterns of care. Consequently, generalization from the experience of pediatric cancer centers is questionable, and the opportunity to test and achieve advances in diagnosis and treatment may be subject to selection bias. PMID- 8490878 TI - Family coping. Supportive and obstructive factors. AB - Successful coping with pediatric cancer enables the family to participate in the effective care of the child. This article focuses on those family variables associated with coping and adjustment to pediatric cancer. Among the variables most commonly noted as risk factors are the following: low socioeconomic status, concurrent stresses, low level of support, pre-existing serious psychologic problems in a family member, and inadequate coping resources. Implications of these risk factors for poor coping are discussed as well as recommendations for further investigation. PMID- 8490879 TI - The role of adolescents in decisions concerning their cancer therapy. AB - Because adolescents are codified as incompetents, their health care decision making authority often is encroached upon. When a teenager develops a serious disease such as cancer, others are even more likely to appropriate decision making authority than under normal circumstances. Adolescents can contribute to decisions concerning their treatment provided certain guidelines are used. These guidelines stem from bioethical concerns and our understanding of the development in cognitive ability related to decision-making. This article summarizes considerations relating to each of these two areas. Because the clinical stage of the malignancy also affects bioethical concerns, the adolescent's role in decision-making at the time of initial diagnosis and recurrence are discussed. PMID- 8490880 TI - Reimbursement issues. PMID- 8490881 TI - Financing care for children with cancer. AB - Although childhood cancers are rare, cancer is the second leading cause of death among children. Over the course of the last 2 decades, improved therapies have dramatically reduced the number of children who die of cancer. However, the incidence of cancer among children has not fallen. Consequently, the number of children who survive cancer has increased rapidly. As a result, greater attention needs to be paid to the resources available to meet the long-term medical, rehabilitative, psychologic, and social needs of children with cancer. PMID- 8490882 TI - Views of childhood cancer survivors. Selected perspectives. AB - Candlelighters Childhood Cancer Foundation surveyed approximately 300 off treatment childhood cancer survivors as well as a comparison group of young adults who had not experienced cancer. Focused group interviews, conducted by a childhood cancer survivor, augmented the questionnaire findings. Selected results include: (1) survivors reported feeling more positive than their peers; (2) self reported health status was more negative for survivors than their peers; (3) survivors reported more worries surrounding cancer-related illnesses. Conversely, they reported fewer general health worries than their peers. In addition, survivors need services such as information, counseling (interpersonal and career), and meetings with other survivors. These findings suggest the need for improved programming by health care providers during and after treatment, as well as the importance of a national survivor network, to address the unique needs of the off-treatment childhood cancer survivor. PMID- 8490883 TI - Surgical management of pelvic and extremity osteosarcoma. AB - Between 60-80% of all patients with osteosarcomas of the pelvis and the extremities can now be safely treated with limb-sparing surgery. Results (as defined by rates of local recurrence, overall survival, and function) are equal to or better than those associated with amputation. Successful use of limb sparing procedures, however, depends on a well-developed surgical plan. An understanding of the biologic behavior and growth patterns of these lesions is fundamental. Staging of the primary tumor must involve a full complement of imaging modalities, including plain radiography, bone scintigraphy, computerized axial tomography (CAT), magnetic resonance imaging (MRI), and angiography. The biopsy must be well placed to reduce the possibility of tissue contamination, which is a common reason for amputation. Restaging is necessary before surgery for patients who have undergone neoadjuvant therapy; there is recent evidence that preoperative therapy may make limb-sparing surgery possible in more than 50% of patients who otherwise would have required amputation. Relative contraindications to limb-sparing surgery include major involvement of the neurovascular bundle, pathologic fracture, inappropriate biopsy site, infection, immature skeletal age, and extensive muscle involvement. Each of these factors is relative, and patient selection decisions must be made on an individual basis. Limb-sparing surgery consists of the following three phases: tumor resection, skeletal reconstruction, and soft tissue and muscle transfers. The range of reconstruction techniques has been broadened by developments in bioengineering. Among the more commonly used techniques are custom endoprostheses and allograft replacements. Future progress in induction regimens and reconstructive techniques will undoubtedly enable limb-sparing surgery to be a satisfactory alternative to amputation in even more patients. PMID- 8490884 TI - Dietary cancer prevention in children. AB - Children may be targets of dietary intervention for the prevention of childhood cancer or to establish dietary habits that may prevent cancer later in life. With respect to the former, there are few etiology studies to suggest that diet plays a major role in the cause and prevention of childhood cancer. The nature of the association of diet and adult onset cancer suggests that long-term exposure is needed, and the limited dietary exposure of children may not provide sufficient opportunity for dietary carcinogenesis. Potentially more significant is the opportunity to prevent adult onset cancer by interventions begun at young ages. Studies document the need to improve the dietary knowledge and practices of young people. Evidence also is available that indicates the feasibility of achieving dietary improvement by school-based and other intervention models. PMID- 8490885 TI - Family issues. PMID- 8490886 TI - Young adults 16-21 years of age at diagnosis entered on Childrens Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols. Results of treatment. AB - BACKGROUND: Scant data are available on event-free survival (EFS) for young adults with leukemia who were 16-21 years of age at diagnosis. In acute lymphoblastic leukemia (ALL), it is well recognized that children have a better EFS compared with adults, whereas for acute myelocytic leukemia (AML), EFS results seem to be similar. To determine the appropriate treatment for young adults with leukemia, outcome data are essential. METHODS: Young adults entered on the Childrens Cancer Group (CCG) 100 series ALL protocols and the CCG 213 AML protocol were analyzed for EFS and survival. Prognostic factors for EFS also were determined. RESULTS: The actuarial EFS for 143 young adults with ALL treated on the CCG 100 series ALL protocols was 64 +/- 4% at 4 years and 59 +/- 4% at 6 years. The major adverse prognostic feature was leukocyte counts greater than 50,000/microliters. The actuarial EFS for 79 young adults with AML entered on CCG 213 was 32.2 +/- 5.3% at 2 years and 28.6 +/- 5.3% at 3 years. CONCLUSIONS: Young adults with ALL treated on CCG protocols have a 6-year EFS of approximately 60%. This is similar to the EFS for patients 10-15+ years of age at diagnosis treated on the same protocols and better than EFS results reported from most adult trials. Young adults with AML had a slightly inferior outcome compared with younger children. PMID- 8490888 TI - Fertility and pregnancy after treatment for cancer during childhood or adolescence. AB - Because most children and adolescents with cancer now survive, issues regarding the late effects of therapy, including fertility and the health of offspring, are increasingly important. This article summarizes the literature regarding issues related to fertility in survivors of cancer, including actual fertility, gonadal function, menarche, menopause, and birth defects and cancer in the offspring. Radiation therapy to the gonads and alkylating agent chemotherapy, either alone or in combination, impair actual fertility in survivors of childhood and adolescent cancer. Males are particularly affected by alkylating agents, and females who have had radiation therapy to the abdomen have decreased fertility and an increased risk of adverse pregnancy outcomes. Consequently, these women should be followed up as high-risk obstetrical patients. Offspring of survivors of cancer appear to have little risk of childhood cancer or birth defects. Thus, in most instances, survivors of cancer should not be discouraged from having children and can expect a good outcome of pregnancy. This article concludes with advice to survivors and clinicians who counsel survivors. PMID- 8490887 TI - Care and treatment of long-term survivors of childhood cancer. AB - With the advances in the therapy of childhood cancers over the past 30 years, many children who are now cured of their cancer are moving into adulthood. These patients have, in many cases, been exposed to multiple therapeutic modalities (chemotherapy, radiation, and/or surgery), and in recent years have experienced more and more intensive therapies. Potential late sequelae can involve almost any organ system, but can be predicted, in part, by the chemotherapy or radiation that individuals may have received. These complications may be categorized by their timing relative to the discontinuation of therapy: early (under 5 years), intermediate (5-20 years), or very late (over 20 years). Four potential late sequelae are reviewed (thyroid, cataracts, renal, and osteoporosis), and recommendations are made for screening of at risk individuals for these long-term complications. The need for long-term follow-up of this unique group of individuals is critical as we attempt to completely define the risks and benefits of our therapeutic efforts. PMID- 8490889 TI - Progress in the treatment of adolescents with acute lymphoblastic leukemia. AB - BACKGROUND AND METHODS. The authors studied the clinical and biologic features and treatment response of 358 children with acute lymphoblastic leukemia (ALL), including 90 adolescents, treated on a single multiagent protocol (St. Jude Total Study XI, 1984-1988). This was done to clarify whether the disease differed in adolescents and to determine the degree of improvement in treatment outcome produced by this modern intense chemotherapy. RESULTS: Compared with the younger children (1-9 years of age; infants 1 year old or younger excluded; n = 257), adolescents (10-18 years of age; n = 90) were significantly more likely to have adverse prognostic features, including T-cell phenotype, L2 blast cell morphologic characteristics, blasts with negative findings for common ALL antigen, and ploidy other than hyperdiploidy greater than 50. Eighty-six of the 90 (96%) adolescents achieved a complete remission, a rate similar to that of the children (97%). Although the event-free survival (EFS) of adolescents was shorter than that of younger children (5-year EFS of 66 +/- 8% versus 75 +/- 5%, respectively; P = 0.04), in this analysis of consecutively treated patients with ALL it showed a significant statistical and clinical improvement as compared with that in our previous study (St. Jude Total Study X, 1979-1983; 5-year EFS rate of 66 +/- 8% versus 37 +/- 5%, respectively; P < 0.001). Within the adolescent group treated on Total Study XI, the EFS was worse for those older than 15 years of age than for those 10-14 years old (46 +/- 15% versus 75 +/- 8%, respectively; P = 0.007). Toxic effects primarily included myelosuppression without severe sequelae. Approximately 96% of the therapy was administered in the outpatient setting. CONCLUSIONS: The increased frequency of unfavorable clinical and biologic features undoubtedly accounts for the poorer prognosis of adolescents with ALL, a conclusion supported by the lack of independent prognostic importance of age in this study. The authors conclude that approximately two-thirds of adolescents can be cured when treated with this intensive but tolerable therapy, showing that this form of treatment significantly has changed the prognosis of adolescents with ALL. PMID- 8490890 TI - Issues in the consideration of intervention strategies in long-term survivors of childhood cancer. AB - With the improved survival of children with cancer, increased attention is being focused on the health status of survivors. The ultimate objective of this research is to use the results to design and test rational intervention strategies directed toward reduction of morbidity and mortality associated with the diagnosis and successful treatment of cancer. After treatment and patient characteristics that confer a high risk for adverse sequelae are identified, intervention programs targeting primary or secondary interventions must be actively pursued. Primary interventions would include modifications to cancer treatment protocols to maintain a high degree of effectiveness but reduce the occurrence of late effects. Opportunities exist for secondary intervention research in a number of areas, including second cancers (smoking cessation/prevention, early detection, chemoprevention), cardiopulmonary dysfunction (diagnosis and treatment of comorbid disease and promotion of healthy life style practices), and reproduction/genetic risks (management, counseling, networking). It is likely that testing of intervention strategies will require collaborative studies involving a multidisciplinary team of investigators and a multi-institutional structure for access to a suitable survivor population. PMID- 8490891 TI - Transition to adult health care for adolescents and young adults with cancer. AB - As the prognosis for children and adolescents with cancer improves, we must reconsider how we will provide care to the adolescents and young adults who have survived these conditions. On the premise that the global needs of adults are best served by health care obtained in the adult health-care system, the case is made for transition from pediatric to adult-oriented health care for adolescents and young adults with cancer. The benefits of transition, barriers to implementation, and models of care are discussed. PMID- 8490892 TI - Pediatric cancer in the United States. A preliminary report of a collaborative study of the Childrens Cancer Group and the Pediatric Oncology Group. AB - BACKGROUND: Cancer is the second leading cause of death in children younger than 15 years. Although 5-year survival rates have increased dramatically for many childhood tumors, more than 100,000 person-years of life are lost to childhood cancer each year. The exact proportion of pediatric patients with cancer who receive care at centers that use up-to-date therapeutic protocols (such as those affiliated with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG) is unknown. METHODS: Based on residence at the time of diagnosis, observed numbers of pediatric cancer cases seen by member institutions of the CCG and the POG in 1989 and 1990 were compared with the expected number of cases. Expected values were calculated from incidence rates obtained from the Surveillance, Epidemiology and End Results Program and population counts obtained from the US Census Bureau. RESULTS: Results indicate that more than 90% of children younger than 15 years who have a diagnosis of malignant neoplasm are seen at an institution that is a member of either CCG or POG. The highest proportion seen occurs in the youngest (0-4 years) age group, and the proportion declines steadily with increasing age. CONCLUSIONS: There are specific regions within the United States where the observed number of cases was substantially less than the expected number, including areas of Texas, Idaho, and Virginia. Although the exact reasons for these potential deficits are unknown, additional study of these areas is recommended. PMID- 8490893 TI - Children and cancer. A perspective from the Cancer Therapy Evaluation Program, National Cancer Institute. AB - The Cancer Therapy Evaluation Program, National Cancer Institute (CTEP, NCI) strongly supports the role of controlled clinical trials in improving the care of children with cancer, and particularly the central role that the pediatric Cooperative Groups play in this process. Trends that threaten the ability to perform these trials include the increasingly limited financial resources available for clinical investigations and the sentiment within some circles that controlled clinical trials may be inappropriate for ethical reasons. The inherent risks of accepting a new therapy without rigorous comparison to existing therapy strongly support the need for randomized trials with adequate accrual to answer important therapeutic questions in a timely and reliable fashion. Retrospective analysis of multiple clinical trials is one method for identifying compelling hypotheses to be tested prospectively. Using this method, we have demonstrated the association between doxorubicin dose intensity and positive response and outcome for patients with Ewing sarcoma and osteosarcoma, thereby providing direction for the selection of important therapeutic questions to be addressed in future clinical trials for these malignancies. PMID- 8490894 TI - Biologic and immunologic approaches to comprehensive therapy for pediatric malignant conditions. Laboratory-clinical interaction. AB - Cooperative integration of laboratory and clinical trial data has provided striking improvement in the treatment of pediatric malignant conditions over the last 2 decades. If attempts are made to individualize therapy to the specific disease and prognostic treatment subgroups for each pediatric malignant condition, the combination of surgery, radiation therapy, and chemotherapy can put the vast majority of patients into a complete clinical remission, with apparent cure for more than half of these patient. Depending on the disease type, treatment failure, when it occurs, is usually the result of recurrent, distant, metastatic disease that is refractory to prior treatment and simultaneously refractory to treatment approaches not yet used for the patient who has had a relapse. The clinical research challenge with these pediatric malignant neoplasms is to identify those children who are harboring microscopic amounts of residual tumor before their relapse and develop effective combined well-tolerated treatment approaches that can be initiated in those patients. These additional treatment approaches should complement rather than duplicate the biologic mechanisms that had been used to initiate remission to eradicate residual tumor without cross resistance. Ongoing laboratory and clinical research approaches are developing and testing the potential of biologic/immunologic therapeutics. The broad application of these principles to clinical oncology will be facilitated by the integrated laboratory-clinical testing that is being accomplished through cooperative pediatric clinical research trials. PMID- 8490895 TI - Treatment compliance in childhood and adolescence. AB - Experience reveals that there is significant noncompliance with self-administered medication, especially in chronic conditions such as cancer. Noncompliance transcends the boundary of disease categories and age group. However, this is most prevalent during the adolescent years when the process of transition from parental dependency to autonomy produces confusion as to who is responsible for administration of medication. Noncompliance can result in the misjudgment of efficacy of a drug or regimen that may necessitate additional tests, alteration of dose, treatment course, and hospitalization. Currently in the United States, a large percentage of pediatric cancer patients are treated according to research protocols. In a research setting, noncompliance can result in erroneous or inconsistent findings, potentially affecting investigational results. With the availability of venous access ports and sophisticated, yet easy-to-operate pumps, increasingly, it is possible to administer parenteral medications at home. This adds a new dimension to the self-administration of medication that previously concerned mainly oral therapy. Various factors concerning the patient, disease, health providers, and treatment characteristics determine how well a given regimen is adhered to. Because a significant number of determinants are involved, it is often not possible, with any degree of certainty, to identify noncompliers or to predict the level of patient adherence to the treatment. Major factors in any successful therapy include the availability of effective medications and compliance with therapy regimen. With the advent of more successful treatments for childhood and adolescent cancer, the compliance factor is gaining greater importance because therapy currently is given with curative, rather than palliative intent. The availability of questionnaires, tests, and devices can help, to some extent, examine the degree of patient compliance. Family and social support, individualized programs, reminders to reduce forgetfulness, personalized needs assessment, and education can reduce noncompliance. Compliance is a complex and multifaceted issue that is still poorly understood and requires further investigation. PMID- 8490896 TI - Cancer in adolescents and young adults psychosocial aspects. Long-term survivors. AB - Survivors of cancer diagnosed during adolescence and young adulthood have had to muster the resources to cope with cancer treatment while accomplishing the tasks unique to this developmental period, tasks such as the accomplishment of economic and emotional independence, capacity for intimacy, solidification of career goals, and formation of a comfortable identity. Studies of survivors of childhood cancer have not found major psychiatric disorders but have pointed out some adjustment difficulties, such as increased health concerns, worries about the development of second neoplasms, increased somatic complaints, and academic problems. Marriage may be delayed, and women, unlike men, worry about their fertility and the health of their future offspring. Survivors of both genders do not appear to be troubled by obvious-to-the-observer physical sequelae. Future studies should examine the quality of life issues pertinent to the successful accomplishment of adult tasks and should include assessment of the facilitators and impediments to carrying out these tasks, particularly during the transition from adolescence into young adulthood. The ultimate goal of the above assessments is to permit not only survival but quality survival. PMID- 8490897 TI - Preoperative multimodality treatment of large soft tissue sarcomas. How can we get more (function) from less (surgery)? PMID- 8490898 TI - The efficacy of preoperative 5-fluorouracil, high-dose leucovorin, and sequential radiation therapy for unresectable rectal cancer. AB - BACKGROUND: The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5 FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer. METHODS: Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV 5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins. RESULTS: The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%). CONCLUSIONS: These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer. PMID- 8490899 TI - Nonepiphyseal giant cell tumor of the long bones. Clinical, radiologic, and pathologic study. AB - BACKGROUND: Giant cell tumors (GCT) usually involve the epiphyses of long bones and only rarely involve the metaphysis or diaphysis without epiphyseal extension. METHODS: This report presents the clinical and pathologic features of 14 patients with metaphyseal and diaphyseal GCT. Of these tumors, 10 were metaphyseal; 2, metadiaphyseal; and 2, diaphyseal. RESULTS: The sites of involvement included the proximal tibia in six patients, distal radius in three, proximal fibula in one, distal fibula in one, distal ulna in one, proximal humerus in one, and distal femur in one. Radiographically, the tumors were lucent, and the majority were sharply marginated without sclerosis. By contrast with conventional epiphyseal GCT, which generally appear in the mature skeleton, a large proportion (50%) of the GCT in this series were in patients who had open epiphyseal growth plates. Despite the unusual clinical presentation, the behavior of metaphyseal and diaphyseal GCT was similar to that of the typical epiphyseal GCT. There was a 43% recurrence rate after curettage in this series. CONCLUSIONS: It is important to distinguish this subset of GCT from other giant cell-rich lesions more common in these sites, including aneurysmal bone cyst, osteosarcoma, and nonossifying fibroma. PMID- 8490900 TI - A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma. AB - BACKGROUND: Based on prior experience with dacarbazine (DTIC) and an outpatient interleukin-2 (IL-2) regimen, the current study was conducted to improve the antitumor efficacy and assess the immunologic interactions between chemotherapy and IL-2. METHODS: Thirty-two patients were registered onto a treatment program, which included DTIC 750 mg/m2 with cisplatin 100 mg/m2, each by intravenous bolus on day 1. Recombinant IL-2 was administered on an outpatient basis intravenously by 15-30-minute infusion (24.0 x 10(6) IU/m2) daily on days 12-16 and 19-23 of a 28-day cycle for three cycles and then every 42 days for responding patients. RESULTS: There were responses in 13 of the 32 registered patients (41% response rate), including five complete and eight partial remissions. Responses in the liver, lung, spleen, lymph nodes, and soft tissue sites were noted. The median duration of response was 8.0 months (range, 3.0-20.0+ months), and the overall median survival duration was 10.2 months. Three patients (9%) are alive, free of disease, without any treatment at 32.0+, 36.0+, and 42.0+ months after initiation of treatment. Only minor nephrotoxicity was observed, and treatment delays were rare. CONCLUSIONS: Additional chemotherapeutic, hormonal, or biologic agents may be added to enhance efficacy further if they have toxicities that do not overlap. PMID- 8490901 TI - Bromodeoxyuridine labeling for S-phase measurement in breast carcinoma. AB - BACKGROUND: The S-phase fraction relates to proliferation, an important determinant of tumor behavior, and has been measured most accurately with the DNA precursor tritiated thymidine (TT). The TT labeling index (LI) is a strong stage independent prognostic indicator for breast carcinoma. The thymidine analogue 5 bromodeoxyuridine (BrdU) is also incorporated into DNA and has the advantage over TT of immunohistochemical detectability rather than requiring autoradiography, but it is less well studied in breast carcinoma. This report demonstrates the equivalence of TT and BrdU LI and explores the relationships between LI and other biologic measurements. METHODS: The LI of 234 consecutive breast carcinomas were measured with TT as was a subsequent series of 450 cases with BrdU, both by incubation in vitro. RESULTS: The mean BrdU LI was 6.4 +/- 0.3% in comparison with 6.9 +/- 0.4% in the prior TT series. LI was unaffected by storage for 24 hours at 4 degrees C before labeling with BrdU. The BrdU and TT LI both correlated: (1) positively with tumor size, histologic type, nuclear size, the number of axillary metastases, the level of DNA ploidy, and the percent S-phase by flow cytometry and (2) negatively with the age of the patient and the levels of estrogen receptor and progesterone receptor measured either by ligand binding or by immunohistochemistry. CONCLUSIONS: BrdU labeling in vitro was an advantageous method for measuring S-phase fraction in breast carcinoma that produced results comparable to those from TT labeling. It should be equally effective for breast cancer kinetic classification and prognosis and is a suitable standard to evaluate newer methods for measuring cellular proliferation. PMID- 8490902 TI - Immunocytochemical assay for estrogen receptor with monoclonal antibody D753P gamma in routinely processed formaldehyde-fixed breast tissue. Comparison with frozen section assay and with monoclonal antibody H222. AB - BACKGROUND: Estrogen receptor (ER) immunocytochemical assay (ICA) can be a useful procedure in patients with breast cancer. The authors sought to study the utility of monoclonal antibody D75P3 gamma (D75) in paraffin-embedded sections of breast cancers. METHODS: Sixty-seven cases of breast cancer were studied by ICA for ER using monoclonal antibody D75 in routinely processed formaldehyde-fixed paraffin embedded tissue, employing ficin predigestion of sections before application of D75. The results were tabulated using a modified histochemical score (HS). In 59 cases, frozen sections of tumors were also studied with D75. In 40 cases, paraffin-embedded sections were stained with both D75 and monoclonal antibody H222 (which is commercially available). Quantitative biochemical ER assays were performed by the standard dextran-coated charcoal method. RESULTS: Statistical analysis of the data showed a highly significant correlation (P < 0.0001) between biochemical ER and paraffin-embedded section HS using D75. The results of frozen section assay and paraffin-embedded section assay using D75 were also highly correlated (P < 0.0001). In addition, paraffin-embedded section HS using D75 correlated well with paraffin-embedded section HS using H222 (P < 0.0001). However, D75 HS generally were higher than H222 HS because of the more intense staining with D75, and this difference was statistically significant (P < 0.0001). Assuming that the biochemical ER data were "true," paraffin-embedded section ICA with D75 had a diagnostic sensitivity of 100%, a diagnostic specificity of 70%, a positive predictive value of 89%, and a negative predictive value of 100%. The results of biochemical ER status and paraffin-embedded section D75 ICA ER status agreed in 61 of 67 cases (91%). In all six cases where the ER status differed, the biochemical ER status was negative, and the ER status by ICA with D75 was positive, leading the authors to suspect that some of these cases may have been biochemical false-negative findings. CONCLUSIONS: It was concluded that ICA for ER with D75 using a 2-minute ficin predigestion of formaldehyde fixed paraffin-embedded tissue is an acceptable alternative to frozen section ICA. In addition, paraffin-embedded section ICA with D75 is easier to interpret than frozen section ICA, and the results are superior to ICA with H222 on paraffin-embedded sections. PMID- 8490903 TI - Age-dependent growth rate of primary breast cancer. AB - BACKGROUND: Currently, there have been no reports of clear-cut beneficial effects of regular screening with mammography at a mean screening interval of 2 years in women younger than 50 years of age. It may be that, because of a higher growth rate of breast cancer, more frequent screening is necessary if any effect is to be observed in this age group. However, good quantitative estimates for the growth rate in different age groups are lacking. METHODS: The study group consisted of cancers diagnosed in women who participated in a screening program with serial mammography available. The growth rate, expressed as the tumor volume doubling time, was calculated on the assumption of exponential growth. The analysis was based, not only on the increase in tumor volume for cancers with at least two mammograms showing a measurable tumor nucleus shadow (n = 85), but also on censored values, calculated for cancers showing no growth (n = 6) and for cancers showing only a measurable tumor nucleus shadow on the mammogram at diagnosis (n = 109). In calculating these latter growth rates, the density of the breast parenchyma was taken into account. RESULTS: The median volume doubling time of the primary breast cancers diagnosed in women aged 50-70 years was 157 days (95% confidence limits, 121-204 days). This was significantly longer than in women younger than 50 years of age at diagnosis (80 days; 95% confidence limits, 44-147 days). Primary breast cancer in women older than 70 years of age at diagnosis grew even more slowly (median, 188 days; 95% confidence limits, 120 295). CONCLUSIONS: To observe a beneficial effect of screening, if any, for women younger than age 50 years, more frequent screening than in the older age group is necessary. PMID- 8490904 TI - Estimating cervical cancer incidence in the Hispanic population of Connecticut by use of surnames. AB - BACKGROUND: The problem of estimating cancer incidence in the growing population of Hispanic women in the Northeastern United States has received little attention. METHODS: Age-specific incidence rates (1980-1988) for invasive and in situ cervical cancer for Hispanic women were estimated by matching individual surnames in the population-based Connecticut Tumor Registry with the 1980 census list of Spanish surnames. Maiden names, obtained from death records of women previously receiving diagnoses of invasive cervical cancer, also were matched with the Spanish-surname list. RESULTS: Estimated age-specific invasive cervical cancer rates for Hispanic women, based on matching individual surnames in the registry with the Spanish-surname list, were higher than rates for all white women in all age groups and at least as high as those for all black women in most age groups. Comparison of maiden names with individual surnames for deceased women, however, suggested that use of individual surnames resulted in some misclassification of Hispanic ethnicity. CONCLUSIONS: The findings indicated that the estimation of cancer rates for Hispanic women in Connecticut could be improved by obtaining maiden names of all women receiving cancer diagnoses. PMID- 8490905 TI - The influence of progesterone and androgens on the growth of endometrial carcinoma. AB - BACKGROUND: The prognosis for endometrial cancer is correlated to the proliferative activity, expressed as the fraction of cells in the synthesis phase (S-phase fraction [SPF]). Progesterone has an antiproliferative effect on the normal endometrium. Its effect in endometrial adenocarcinoma has not been investigated in such detail. METHODS: The SPF in tumor tissue and serum levels of progesterone, androstenedione, and testosterone were measured in 78 postmenopausal women with the diagnosis of endometrial adenocarcinoma. RESULTS: No correlations were found between the SPF and androstenedione or testosterone level. No linear correlation between the progesterone concentration and the SPF was revealed when all the patients were analyzed. The material was then divided into subgroups according to the tumor grade and ploidy level. A stepwise analysis based on the progesterone concentration showed that, in well-differentiated and moderately differentiated tumors, the growth rate, expressed as the SPF, fell when progesterone reached a serum level above 0.8 nM. CONCLUSIONS: Endogenous progesterone plays a role in the control of the tumor's proliferation activity and, consequently, might be significant in the prognosis. PMID- 8490906 TI - Prognostic value of steroid hormone receptors for 5-year survival in stage II endometrial cancer. AB - BACKGROUND AND METHODS: In a prospective study, the 5-year survival of 57 patients with Stage II endometrial cancer was correlated to the estrogen (ER) and progesterone (PR) receptor concentrations using the dextran-coated charcoal (DCC) technique. The cutoff level was 3 fmol/mg of protein for ER and 6 fmol/mg of protein for PR. RESULTS: An histopathologic examination of the tumor tissue samples before treatment demonstrated that 16% of the cases (9 patients) were well-differentiated (Grade 1), 45% (26 patients) moderately differentiated (Grade 2), and 39% (22 patients) poorly differentiated (Grade 3). Only 3 were ER negative, whereas 19 were PR negative. The mean concentrations for ER and PR were 106 and 162 fmol/mg of protein, respectively. All patients received standard treatment, including preoperative irradiation. The total 5-year survival rate was 82% (47 of 57 patients). Deep myometrial invasion was important in Grade 3, but not in Grades 1 and 2; in these two grades, all five patients with deep infiltration survived. There was a correlation between receptor concentration and grade, with a significant difference between Grades 1 and 2 versus Grade 3. All patients who were ER negative survived, as did all patients who were PR negative in Grades 1 and 2. Of the patients with Grade 3 disease who died, four of six (67%) were PR negative. Of the patients with Grade 3 disease who survived, 10 of 16 (63%) were PR negative. CONCLUSIONS: Patients who survived for 5 years did not have significantly different ER and PR concentrations than those who died. The mean ER and PR concentrations in patients who survived were 99 and 159 fmol/mg of protein, respectively, compared with 108 and 178 fmol/mg of protein, respectively, for those who died. PMID- 8490907 TI - Dietary factors and the risk of endometrial cancer. AB - BACKGROUND: Endometrial cancer is associated with overweight, but little is known on its possible relationship with specific aspects of diet. METHODS: The relationship between dietary factors and the risk of endometrial cancer was investigated in a case-control study conducted in Switzerland and Northern Italy on 274 patients with histologically confirmed endometrial cancers and 572 control subjects admitted to the hospital for acute nongynecologic disorders that were not hormone related, metabolic, or neoplastic. RESULTS: Significant direct associations were observed with (1) the total energy intake (odds ratio [OR] for the highest versus the lowest consumption tertile = 2.7) and, after allowance for energy intake, (2) the frequency of consumption of most types of meats, eggs, beans or peas, added fats (OR for total added fat = 2.5), and sugar (OR = 2.5). Significant protection, of the order of 40-60% reduction in the highest versus the lowest consumption tertile, was conferred by elevated intake of most vegetables and fresh fruit and whole grain bread and pasta. This was reflected in the low OR for the highest tertiles of intake of beta-carotene and ascorbic acid (OR for the highest versus the lowest consumption tertile after allowance for energy intake = 0.5). CONCLUSIONS: The current study suggests that, aside from the predictable adverse effects of overeating and consequent overweight, some qualitative aspects of the habitual diet may also be associated with the risk of endometrial cancer, chiefly, the intake of animal proteins and fat (directly) and of fresh fruit, vegetables, and fibers (inversely). PMID- 8490908 TI - Leukoerythroblastic anemia in metastatic prostate cancer. Clinical and prognostic significance in patients with hormone-refractory disease. AB - BACKGROUND: The clinical and prognostic significance of leukoerythroblastic anemia (LKEA) in patients with metastatic prostate cancer and, in general, patients with disseminated solid tumors is poorly understood. Therefore, the authors studied a population of patients with metastatic prostate cancer refractory to hormonal therapy to assess the incidence, clinical features, and prognostic implications of LKEA. METHODS: The medical records of 106 patients with hormone-refractory prostate cancer metastatic to bone seen at the Tucson Veterans Affairs Medical Center between 1985 and 1991 were reviewed retrospectively. The clinical and laboratory data, number of packed erythrocyte transfusions required, and length of survival from the time of diagnosis of hormone-refractory disease until last follow-up visit or death were investigated in 91 identified patients. RESULTS: Twenty-six of 91 patients (28.6%) were found to have LKEA. LKEA developed before or at the time of diagnosis of hormone refractory disease in 8 patients and after diagnosis of hormone-refractory disease in 18 patients. The presence of LKEA was associated with significantly lower hemoglobin levels and platelet (Plt) counts and significantly higher total bilirubin, lactic dehydrogenase (LDH), and alkaline phosphatase values (P < 0.05). Leukopenia (< 4.0 x 10(9)/l leukocytes), thrombocytopenia (< 150 x 10(9)/l Plt), elevated LDH levels (> 220 U/l), and laboratory evidence of disseminated intravascular coagulation (DIC) were more common in patients with LKEA than in those without LKEA (P < 0.01). Microangiopathic hemolysis was seen in only 2 of 91 patients (2.1%). Patients with LKEA had significantly greater transfusion requirements compared with patients without LKEA (P < 0.0001), but the median survival length was not significantly different (9 months versus 11 months, respectively). The presence of DIC and LDH levels of 500 U/l or greater in patients with LKEA was associated with a poor prognosis. CONCLUSIONS: LKEA is a relatively common finding in patients with hormone-refractory metastatic prostate cancer and is associated with greater transfusion requirements. Its presence, however, does not affect survival significantly. PMID- 8490909 TI - A phase II study of constant-infusion floxuridine for the treatment of metastatic renal cell carcinoma. AB - BACKGROUND: Twenty-nine patients with metastatic renal cell carcinoma (RCC) were treated with constant-infusion floxuridine (FUdR, Roche Laboratories, Nutley, NJ). METHODS: The initial dosage was 0.075 mg/kg/day for 14 days every 28 days and was increased or decreased by 0.025-mg/kg/day increments at each subsequent cycle until the maximum tolerated dose (MTD) was achieved. RESULTS: All patients were fully assessable. One (4%) patient had a complete response, 5 (17%) had a partial response, 13 (50%) had stabilized disease, and 10 (34%) had progressive disease. The treatment-limiting toxic effect was diarrhea, and the median tolerated dosage was 0.1 mg/kg/day for 14 days every 28 days (range, 0.05-0.275 mg/kg/day). Five of the six responses occurred at a dosage of 0.1 mg/kg/day or less, which was achievable in most patients. Patients who reached their MTD without achieving a complete or partial response were switched to circadian infusion floxuridine to determine whether an increased dose intensity could be administered and whether this would translate into additional responses. A higher median tolerated dosage of 0.15 mg/kg/day was achieved with circadian administration; however, no additional responses were observed. The median survival time was 891 days after the diagnosis of metastatic RCC and 445 days after the institution of floxuridine therapy. CONCLUSIONS: Constant-infusion floxuridine is active against metastatic RCC and produces a response rate that appears to be comparable to that of circadian administration of floxuridine. PMID- 8490910 TI - Occupational physical activity and the incidence of cancer of the breast, corpus uteri, and ovary in Shanghai. AB - BACKGROUND: A sedentary life style has been consistently associated with an increased risk of colon cancer, but the evidence for its association with breast and other gynecologic cancers is limited. METHODS: Occupational information for 3783 incident patients with cancer (breast, 2736; corpus uteri, 452; and ovary, 595) whose disease was diagnosed during the period 1980-1984 was compared with 1982 census data on employment in Shanghai urban areas. The standardized incidence ratios (SIR) of these cancers were estimated for each occupational group classified by job titles and physical activity levels. RESULTS: A significantly increased incidence of breast cancer was found among professionals (SIR = 158), government officials (SIR = 131), and clerical workers (SIR = 143); the incidence was reduced among service workers (SIR = 87) and craftsmen (SIR = 91). Occupational physical activity, as measured by sitting time and energy expenditure, was inversely related to breast cancer incidence, with SIR of 127 131 for inactive jobs (sedentary or low-energy expenditure) and 79-93 for active jobs (long periods of standing or high energy expenditure). Similar associations, although to a lesser extent, were also seen for cancer of the corpus uteri and ovary. CONCLUSIONS: Women with low physical activity occupations had an increased incidence of cancer of the breast, corpus uteri, and ovary; the incidence was reduced among women with high-activity jobs. These findings were consistent with observations from earlier studies and provided further evidence that physical activity may lower the risk of these female hormone-dependent cancers. PMID- 8490911 TI - Comparative evaluation of serum CA 195 and carcinoembryonic antigen in metastatic carcinoma. AB - BACKGROUND: Carcinoembryonic antigen (CEA) is a well-described human tumor associated antigen most useful clinically in colon cancer. However, the clinical usefulness of CEA is limited by the marker's overall poor specificity and low sensitivity in patients with minimal disease. CA 195 is a recently discovered human tumor-associated glycoprotein that can be measured in serum using an immunoradiometric assay. CA 195 is expressed on the membrane of human colon cancer cells and shares an epitope with the Lewis A blood group antigens. The authors initiated a study to compare the clinical utility of serum CA 195 with CEA in patients with advanced cancer. A control population was studied to assess the effects of age, gender, alcohol, and tobacco on the measured levels of serum CA 195. METHODS: Using a solid-phase two-site immunoradiometric assay, serum CA 195 and CEA levels were measured in 71 control subjects and 167 patients with a prior diagnosis of cancer. The tumor histologic types included breast cancer, 49 patients; colon cancer, 38; prostate cancer, 24; lung cancer, 22; gastrointestinal noncolon cancer, 7; and miscellaneous, 27. Among patients with a history of cancer, 124 (74%) had active metastatic disease, and 43 (26%) were without evidence of active disease. The control population was composed of subjects without a history of malignancy. Clinical data collected from them included age, gender, smoking history, and alcohol consumption. RESULTS: In this laboratory, the normal ranges established for CA 195 and CEA in the control group were: 0.0-8.3 U/ml and 0.2-4.2 ng/ml, respectively. In the control subjects, the serum CA 195 level, unlike that of CEA, was not affected by age, gender, alcohol consumption, or tobacco use. In the study population, CA 195 had either equivalent or inferior specificity and sensitivity to CEA in all tumor types. A determination of the additive specificity and sensitivity of CA 195 and CEA did not significantly improve its clinical utility compared with CEA alone. However, CA 195 was significantly elevated in three patients with a prior history of colon cancer thought to be without evidence of active disease. Because all three of these patients had a relapse within the next 1-15 months, CA 195 might identify early relapses of colon cancer in some patients. CONCLUSIONS: Based on these results, it was concluded that CA 195 is not superior to CEA as an indicator of disease activity in advanced colon cancer or other solid tumors. However, studies utilizing CA 195 in the detection of early relapses of colon cancer may be warranted. A review of the English literature revealed that CA 195 might be a useful marker in pancreatic cancer. PMID- 8490912 TI - Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. AB - BACKGROUND: Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. METHODS: A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. RESULTS: The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). CONCLUSIONS: This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed. PMID- 8490913 TI - Brain metastases in osteosarcoma. Report of a long-term survivor and review of the St. Jude Children's Research Hospital experience. AB - BACKGROUND: Brain metastasis has been considered a rare event in osteosarcoma, although with prolonged survival an increasing incidence has been suggested. There have been no prior reports of long-term survivors among patients with this complication. METHODS: The authors describe a child treated for osteosarcoma who is alive and free of disease 8 years after the detection of brain metastases. Of 254 patients with primary osteosarcoma referred to St. Jude Children's Hospital between 1962 and 1989, 13 developed brain metastases, all after relapse or recurrence in another site. Concomitant active lung metastases were present in all of the patients except the one long-term survivor, whose pulmonary disease had responded to treatment with cisplatin and doxorubicin. Log-rank analyses were used to compare survival duration and the frequency of brain metastases among patients treated before and after 1982, when effective multiagent therapy was initiated. RESULTS: Log-rank analyses comparing patients treated before and after 1982 showed that the introduction of effective modern therapy improved survival among patients at risk for brain metastases (i.e., those with recurrent and progressive disease, P = 0.007) but was not associated with a statistically significant increase in the frequency of brain metastases (15.5% versus 4.5%, P = 0.125). CONCLUSIONS: Although the outlook for patients with this complication remains bleak, the resolution of brain metastases after eight courses of ifosfamide in the patient described in this article suggests that enrollment of selected patients in Phase II trials is merited. PMID- 8490914 TI - A phase I study of ifosfamide with Mesna given daily for 3 consecutive days to children with malignant solid tumors. AB - BACKGROUND: The authors conducted a Phase I dose escalation trial of ifosfamide given daily for 3 consecutive days to 29 children with malignant solid tumors. Twenty-eight of these children had received prior chemotherapy. METHODS: Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9). At least three patients in each category were treated at a starting dosage of 2133 mg/m2/d for 3 days. This dosage represented 80% of the total dose delivered in the prior study of ifosfamide given daily over 5 days with dosage escalation of 20% in subsequent cohorts. RESULTS: Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum. Dose-limiting neurotoxicity was seen at 2560 mg/m2/d for the former group, but was not encountered in the latter group. CONCLUSIONS: Delivery of ifosfamide daily for 3 days is feasible and safe at recommended dosages of 2133 mg/m2/d for children with prior exposure to platinum and 3000 mg/m2/d for those without prior exposure. PMID- 8490915 TI - A phase I study of ifosfamide given on alternate days to treat children with brain tumors. AB - BACKGROUND: Ifosfamide with Mesna, given every other day over a 5-day period, was evaluated in 20 children with recurrent or progressive primary brain tumors. METHODS: The patients were assigned to dosage cohorts separated on the basis of prior exposure to cisplatin (n = 10) or the absence of such exposure (n = 10). The initial dose in each treatment arm was 2133 mg/m2 every other day for three doses, which represented 80% of the total dose delivered in our prior study of ifosfamide given daily over 5 days. The dose was escalated by 20% in each of the two subsequent cohorts (2560 mg/m2 and 3072 mg/m2 every other day for three doses). RESULTS: The hematologic toxicity was dose limiting. Prior exposure to cisplatin did not seem to increase the hematologic toxicity. The most frequent and significant metabolic disturbance was hyponatremia, resulting in self-limited seizure activity in three patients. This complication was prevented in subsequent patients by changing the post-ifosfamide hydration fluids from 5% dextrose in quarter normal saline to 5% dextrose in normal saline. CONCLUSIONS: Although no child achieved a complete response, the activity of ifosfamide was demonstrated for a variety of tumors. The recommended dose of ifosfamide in a Phase II study for brain tumors is 3000 mg/m2 given with Mesna every other day for three doses. PMID- 8490916 TI - Primary peripheral nodal lymphoma in children. AB - BACKGROUND: In this series of 208 pediatric patients with non-Hodgkin (NHL) studied from 1971 to 1986, 84 patients (40.4%) had nodal lymphomas; 40 (19.2%) of these patients had peripheral nodal lymphoma and 44 (21.2%) had mediastinal lymphoma. METHODS: Forty pediatric patients with primary peripheral nodal lymphoma were treated at Memorial Sloan-Kettering Cancer Center with the LSA2-L2 protocol from July 1971 to January 1986. Informed consent was obtained from all patients and/or guardians. RESULTS: There were 26 male patients and 14 female patients, with a median age of 10 years. Two patients had Stage I disease, 5 Stage II, 9 Stage III, 8 Stage IVA (< 25% blasts in the bone marrow), and 16 Stage IVB (> 25% blasts in the bone marrow). The last patient with Stage IVB disease was entered in 1977, a time when the philosophy of treatment for leukemia lymphomas had not yet evolved completely. Most of these lymphomas were high-grade lymphoblastic lymphomas, followed by immunoblastic lymphomas and reticulosarcomas. The event-free survival rate of this group of patients was 75%, with all patients having completed therapy, and a median observation time of more than 10 years without therapy. The lymphoma-free survival rate was 80%. Sex, age, and stage were not of prognostic significance. There was no significant difference in survival between patients with lymphoblastic and histiocytic lymphomas (75% versus 64%, respectively). There was no significant difference in survival between the patients with high-grade and medium-grade lymphomas (75% versus 78%, respectively). Lactic dehydrogenase (LDH) in this primary site was not indicative of extent or bulk of disease and did not affect survival negatively. Radiation therapy and dose intensity of chemotherapy influenced survival by promoting rapid and more complete cell kill, helping prevent the emergence of resistant cells. CONCLUSIONS: Although primary peripheral nodal lymphoma usually is disseminated at diagnosis, it is still a highly curable disease when treated aggressively. The lymphoma-free survival rate for patients with primary nodal NHL with marrow involvement is 75%, and this subsequently has led to a different philosophy in the treatment of high-risk leukemias and lymphoma-leukemias with the NY-I and NY-II protocols, with excellent results. PMID- 8490917 TI - The order of administration of chemotherapy and radiation and its effect on the local control of operable breast cancer. AB - BACKGROUND: A delay in administration of radiation therapy has been suggested to increase the risk of local recurrence after breast-conserving surgery. METHODS: The data were retrospectively reviewed from 552 patients in whom treatment consisted of total mastectomy (n = 467) or segmental mastectomy (n = 85), irradiation, and combination chemotherapy. Of these, 463 patients received radiation therapy first, and 89 received chemotherapy first. The pattern of failures was compared between the subgroups according to the order of administration chemotherapy and irradiation and its effect on the local control of disease. RESULTS: The median follow-up time of the local mastectomy subgroup was 133 months; of the segmental mastectomy subgroup, it was 39 months. The incidence of locoregional failure within each subgroup was not affected by the order in which the chemotherapy and irradiation were administered. CONCLUSIONS: These data suggest that delaying irradiation in an effort to reduce the risk of systemic relapse does not increase the risk of local failure. PMID- 8490918 TI - Preoperative multimodality treatment for soft tissue sarcomas. AB - BACKGROUND: Frequently, soft tissue sarcomas (STS) do not present until they are large, thus making local control difficult. Consequently, different methods of preoperative cytoreduction should be evaluated. METHODS: This study evaluated a 10-day preoperative regimen of intraarterial doxorubicin (10 mg/m2/d), with concomitant radiation therapy (25 Gy), administered to 55 adult patients with either Stage T2 (n = 41) or distal Stage T1 (n = 14) STS. Seven of the tumors were low grade. All patients were treated by the Division of Surgical Oncology at the University of Illinois between 1978-1991. RESULTS: This regimen was successful and obviated the need for amputation in 47 patients who underwent wide soft tissue excision, an initial limb-salvage rate of 87%. Complications related to the therapy occurred in 26% of patients, which resulted in additional operative procedures in 7%. The mean follow-up time was 94 months. The 5-year overall survival rate was 69%, with a disease-free survival rate of 51%. Local control was unsuccessful in 15% of the patients. Three additional patients required amputation for recurrent disease (n = 2) or complications of therapy (n = 1), resulting in an ultimate limb-salvage rate of 81%. CONCLUSIONS: The long term results of this preoperative protocol for adults with limb-threatening STS appears to justify the utilization of a multimodality approach. This preoperative regimen was useful in minimizing limb loss in patients with limb-threatening STS. However, intraarterial doxorubicin administration is associated with significant morbidity, and its role in multimodality treatment of STS requires further clarification. PMID- 8490919 TI - Preoperative chemotherapy and radiation therapy for locally advanced primary and recurrent rectal carcinoma. A report of surgical morbidity. AB - BACKGROUND: Complete surgical resection of locally advanced primary and recurrent rectal cancer is often incomplete. Improved tumor downstaging may improve resection rates and local control if postoperative morbidity is not increased. METHODS: The clinical and pathologic records of 119 patients with locally advanced primary and recurrent rectal carcinoma were reviewed to determine the effect of preoperative chemoradiation on postoperative morbidity compared with a control group treated with external beam radiation therapy alone. Group I (56 patients) was treated with 45 Gy of external beam radiation therapy. Group II (63 patients) received 45 Gy of external beam radiation therapy with continuous infusion cisplatin, 5-fluorouracil, or both. RESULTS: Forty-one patients (73.2%) in Group I and 48 in Group II (76.1%) underwent surgical resection. Anal-sparing procedures were performed more frequently in Group II (25%) than in Group I (5.3%, P < 0.05). The overall complication rate for Group I was 51% versus 44% for Group II (P < 0.05) or 1.17 complications per patient in Group I and 0.58 complications per patient in Group II. One patient in each group died of treatment-related septic complications. CONCLUSIONS: It was concluded that the addition of chemotherapy to radiation to treat rectal carcinoma does not result in an increased operative morbidity and may contribute to a higher proportion of patients being treated with anal-rectal-conserving surgical procedures. PMID- 8490920 TI - Pathologic stage III endometrial carcinoma. Prognostic factors and patterns of recurrence. AB - BACKGROUND: This review was done to assess the outcomes and patterns of recurrence in a group of patients with Stage III endometrial carcinoma that might help guide adjuvant therapy. METHODS: A retrospective review was performed of 105 patients treated from 1970-1990 at three institutions. All patients underwent abdominal hysterectomy, with 60 having pathologic node assessment and 45 having cytologic examination of peritoneal washings. A single extrauterine site was involved in 75% of patients; 20% and 5% had two and three sites involved, respectively. All patients received postoperative external beam irradiation to the pelvis or pelvis and paraaortic regions for pathologically positive paraaortic nodes. Actuarial techniques were used to estimate the survival and recurrence rates. RESULTS: The 5-year disease-free survival rate for all patients was 64%. Univariate analysis revealed that the depth of myometrial penetration, the clear cell or papillary serous pathologic type, the histologic grade, and the number of extrauterine sites predicted disease-free survival. Cox regression revealed the grade and pathologic findings to be independent predictors of disease-free survival. The overall 5-year pelvic recurrence rate was 21%, with multivariate analysis revealing the grade to be the strongest prognostic factor. Pathologic findings and the number of involved extrauterine sites were the most important prognostic factors for abdominal recurrence and other sites of distant relapse. CONCLUSIONS: The subgroup of patients with low-grade endometrial tumors or superficial myometrial penetration has a low distant relapse rate. Local control remains the goal of therapy in these patients. Patients with high-grade tumors, deep myometrial penetration, clear cell or papillary serous histologic types, or two or more involved extrauterine sites are at high risk for distant recurrence that may include the abdomen. Investigative strategies delivering aggressive adjuvant therapy are appropriate. PMID- 8490921 TI - Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. AB - BACKGROUND: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease. METHODS: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone. RESULTS: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed. PMID- 8490922 TI - In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines. AB - BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations. PMID- 8490923 TI - Role of brachytherapy in the management of the skull base meningioma. Treatment of skull base meningiomas. AB - BACKGROUND: The treatment of primary and recurrent skull base meningiomas presents a formidable surgical problem. METHODS: Fifteen patients with primary and recurrent skull base meningiomas were treated by means of interstitial irradiation with iodine 125 (125I) seed implantation. The physical characteristics of 125I enabled the authors to administer a minimum tumor dose ranging from 100 to 500 Gy at a low dose rate of 0.05-0.25 Gy per hour. RESULTS: All 15 patients are alive at a median follow-up of 29 months. Of the 15 patients, 2 with calcification and 2 without calcification achieved only partial responses. The remaining 11 patients achieved a complete response. No early or late complications were observed. CONCLUSIONS: From these data, the authors conclude that interstitial irradiation with 125I seeds is an effective, safe, and simple method in the treatment of both recurrent and primary skull base meningiomas. PMID- 8490924 TI - Multivariate analysis of the relationship between survival and the microstage of primary melanoma by Clark level and Breslow thickness. AB - BACKGROUND: The American Joint Committee on Cancer (AJCC) uses both Breslow thickness and Clark level in its staging system for malignant melanoma. Stage I corresponds to Breslow thicknesses less than 1.5 mm and Clark levels II and III. Stage II corresponds to Breslow thicknesses of at least 1.5 mm and Clark levels IV and V. However, most investigators have found Clark level to be of no prognostic significance once Breslow thickness has been taken into consideration by multivariate analysis. METHODS: The authors examined the prognostic significance of Clark level by studying patients in the large database of the John Wayne Cancer Institute. Among 5575 patients with melanoma seen during the past 20 years, complete data on microstaging by both Clark and Breslow methods were available for 3323 patients. The 5-year survival rates were as follows: Clark II, 95%; III, 81%; IV, 68%; V, 47%. The Breslow thicknesses were as follows: < 0.75 mm, 95%; 0.75-1.49 mm, 85%; 1.5-3.99 mm, 66%; > or = 4.0 mm, 46%. RESULTS: By univariate analysis, both Clark level and Breslow thickness were highly significant prognostic indicators (P < 0.0001). By multivariate analysis, Breslow thickness remained significant (P < 0.0001). However, even when Breslow thickness was included in the model, Clark level also remained highly significant (P < 0.0015). CONCLUSIONS: Decisions regarding therapy for patients with clinical Stage I melanoma should consider both Clark level and Breslow thickness of the primary lesion. When there is a discordance between the two methods of microstaging, the AJCC stage should be amended to reflect the least favorable of the two prognostic indicators. PMID- 8490925 TI - Acute and late reactions to radiation therapy in patients with collagen vascular diseases. AB - BACKGROUND: A commonly held belief is that patients with collagen vascular diseases (CVD) have a greater risk of radiation therapy complications than patients without CVD. This impression is based on anecdotal reports, however. METHODS: A group of 61 patients with CVD were compared with a matched control group of 61 patients without CVD. The CVD group included 39 patients with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), 4 with systemic sclerosis (scleroderma) (SSc), 4 with dermatomyositis, and 1 with polymyositis. The control group was matched with respect to age, sex, tumor site and histologic characteristics, treatment aim, general treatment method, radiation therapy technique, site irradiated, radiation dose, date of treatment, and follow-up. RESULTS: Overall, there was no significant difference between the CVD and control groups in terms of acute (11% versus 7%, respectively) or late complications (10% versus 7%, respectively). This was also true when only patients who were treated definitively were considered. Furthermore, none of the patients treated palliatively had complications. Three patients in the CVD group had fatal complications, compared with none in the control group. RA was associated with a slight increase in late complications in the definitively treated patients, whereas SLE was associated with a slight increase in acute reactions. No significant acute or late reactions were observed in the patients with SSc, dermatomyositis, or polymyositis. CONCLUSIONS: In general, these differences are less than expected and not statistically significant. Consequently, from these data, the authors could not show a significant increase in radiation therapy complications for patients with CVD. PMID- 8490926 TI - The Janeway Lecture 1992. Nine decades of radiobiology: is radiation therapy any the better for it? AB - Nine decades have elapsed since Pierre Curie performed the first radiobiologic experiment when he used a radium tube to produce an ulcer on his arm and charted its progress and ultimate healing. A wide range of topics have been investigated in experimental radiation biology from chromosomal aberrations to fractionation effects in normal tissues to the use of neutrons and bioreductive drugs. Many of the strategies used in clinical radiation therapy, including hyperfractionation and accelerated treatment, are firmly based on laboratory experiments conducted in the past. Much current research is focused on understanding the molecular genetics of cancer to identify the genes that are activated or deleted in cells exposed to radiation. Radiobiology has played a key role in shaping radiation therapy into the vigorous, scientifically based, and highly quantitative branch of medicine that it is currently. In addition, research is preparing the field for the future when treatment protocols must be based on molecular rather than cellular biology. PMID- 8490927 TI - The role of iodine-131 and thallium-201 imaging and serum thyroglobulin in the management of differentiated thyroid carcinoma. AB - BACKGROUND: A prospective study was conducted to evaluate the use of iodine-131 sodium scintigraphy, thallium-201 chloride scintigraphy, and quantitative serum thyroglobulin estimation in the detection of differentiated thyroid carcinoma after thyroidectomy and iodine-131 sodium ablative therapy. METHODS: Thirty-one patients with a median age of 45.6 years (range, 20-73 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (> 50 mU/ml), 53 pairs of iodine-131 and thallium-201 scans were performed. Concomitant serum thyroglobulin levels were available for 32 pairs of scans. The presence or absence of thyroid cancer was established by clinical, radiologic, and/or biopsy findings. RESULTS: The concordance between iodine-131 and thallium-201 scan findings in the presence of disease (25 scan sets) was 36%. The concordance in the absence of disease (28 scan sets) was 82%. Iodine-131 scanning was found to be significantly better (P < 0.05) than thallium-201 scanning, in terms of sensitivity (0.8 versus 0.6), specificity (0.96 versus 0.82), accuracy (0.89 versus 0.72), and the predictive value of a positive test (0.95 versus 0.75). The measurement of serum thyroglobulin had a low sensitivity (0.3) in the study but had a specificity of 1.0. CONCLUSION: It was concluded that iodine-131 sodium scintigraphy is superior to thallium-201 scintigraphy and serum thyroglobulin estimation for the detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities provides a higher diagnostic yield. Thallium-201 scintigraphy was especially useful in cases in which iodine 131 scintigraphy was negative and quantitative thyroglobulin levels were elevated. PMID- 8490928 TI - Wound repair after fractionated external beam radiation therapy and concomitant hyperthermia in an experimental rat model. AB - BACKGROUND: Fractionated radiation therapy (RT) with adjuvant hyperthermia (HT) is being used in the treatment of cancer with noted clinical success. However, little information regarding wound repair in tissues receiving this combination therapy is available for comparison of surgical risk. Consequently, this study was undertaken to assess the effects of this combined therapy on wound healing by quantitatively evaluating wound repair using tensile strength measurements. METHODS: Four treatment cohorts were designated: sham control, RT alone (600 cGy/d for 4 days), HT alone (water bath at 41.8 degrees C, subcutaneous temperature of 41.0 +/- 0.5 degrees C for 60 minutes on days 1 and 4), and combined RT and HT. At 1 week after treatment, surgical incisions of the dorsal flank were made. Tensile strength measurements of wounds were obtained at 14 and 21 days after incision. RESULTS: No significant differences were observed in the combined treatment arm (RT and HT) compared with the reduced wound breaking strength of RT alone. Statistically significant differences in tensile strength were seen when the control group or HT alone was compared with RT and HT or RT alone. CONCLUSIONS: Concomitant exposure to fractionated RT and specific HT conditions demonstrated no disproportionate alteration in wound tensile strength compared with radiation exposure alone in this animal model. PMID- 8490929 TI - Dedifferentiation of locally recurrent prostate cancer after radiation therapy. Evidence for tumor progression. AB - BACKGROUND: Untreated or unsuccessfully treated prostatic adenocarcinoma may develop more malignant characteristics as time passes--the phenomenon of tumor progression. Whether this occurs after unsuccessful radiation therapy has not been answered. This study was designed to address that issue. METHODS: The histologic grades at initial diagnosis and at local recurrence were compared in 49 patients who experienced local recurrence after external beam radiation therapy. RESULTS: Tumor grades were assigned using the M. D. Anderson grading system. At the initial diagnosis, the grades were distributed as follows: Grade 1, 18 (37%), Grade 2, 22 (45%); Grade 3, 8 (16%); and Grade 4, 1 (2%). At recurrence, the grades were: Grade 1, 3 (6%); Grade 2, 14 (29%); Grade 3, 14 (29%); and Grade 4, 18 (37%). The shift to higher grades at recurrence was highly significant (P < 0.001). This dedifferentiation could not be accounted for by possible tissue sampling variability, and stepwise multiple variable logistic regression revealed that the only factor predicting for dedifferentiation was the time since treatment. The tumors that recurred later had a significantly higher likelihood to be dedifferentiated than those that recurred early. Patients whose tumors dedifferentiated had a poorer survival than those whose tumors retained their original grade. CONCLUSIONS: The possibilities were considered that the dedifferentiation could arise by tissue sampling error, by persistence and regrowth of high-grade components, by the development of new tumors, or by radiation-induced transformation. None of these mechanisms appeared to explain the data adequately, and it was concluded that the observed dedifferentiation was indeed a manifestation of time-dependent tumor progression. Eradication of the primary tumor is therefore important, not only to allay local symptoms, but also to prevent the emergence of more virulent and potentially lethal tumors. PMID- 8490930 TI - A proposed staging system for chronic myeloid leukemia. AB - A staging system was proposed for chronic myeloid leukemia (CML) that groups patients into three stages (I, II, and III), each with two subclasses (A and B). The system uses pathologic parameters, of which the percentage of blasts in the blood and bone marrow is the most important. CML is defined as a myeloproliferative disorder with molecular or cytogenetic evidence of the translocation of the abl oncogene on chromosome 9 to the break-point cluster region gene on chromosome 22. The proposed staging system is similar to format to the standard TNM system used for many solid tumors. PMID- 8490931 TI - Thymic hyperplasia with hemorrhage simulating recurrent Hodgkin disease after chemotherapy-induced complete remission. PMID- 8490932 TI - The effects of surgical treatment on survival and local recurrence of cutaneous malignant melanoma. PMID- 8490933 TI - Soluble interleukin-2 receptors and cutaneous T-cell lymphoma. PMID- 8490934 TI - Myocardial fibrosis: functional significance and regulatory factors. PMID- 8490935 TI - Rat myocardial tissue lipids and their effect on ventricular electrical activity: influence on dietary lipids. AB - OBJECTIVE: The aim was to investigate the effect of diets with different lipid content on rat myocardial tissue lipid composition and their possible influence on myocardial electrical activity. METHODS: 60 male Sprague-Dawley rats were randomised in three dietary feeding groups. Half the animals were used for the myocardial lipid study and the other half for the ventricular refractory period and ventricular conduction velocity measurements. Synthetic diets of low fat, high fat (predominantly lard fat), and high fat plus marine oil, the last two with cholesterol, were supplied ad libitum for five weeks. After 2-propanol myocardial lipid extraction, lipid fractions were separated by thin layer chromatography and their esterified fatty acids by gas-liquid chromatography. Ventricular refractory period was obtained according to the extrastimulus technique and maximum conduction velocity by ventricular pacing. RESULTS: The experimental diets induced marked changes in fatty acid composition of myocardial phospholipids and in esterified cholesterol content. The high fat group showed a significant decrement in oleic and linoleic acids, with an increment in arachidonic and docosahexaenoic acids in their phospholipid composition. This dietary group had the highest esterified cholesterol content. These changes were related to lowering of maximum ventricular paced heart rate and lengthening of ventricular refractory period, and were partly corrected by marine oil supplement. CONCLUSIONS: Saturated fat diets cause profound changes in myocardial fatty acyl composition which are linked to sustained differences in myocardial electrical activity. These changes can be partly corrected by a moderate fish oil supplement. PMID- 8490936 TI - Ultrastructural demonstration of peroxidative activity and peroxidation in ischaemic and ischaemic-reperfused rabbit hearts. AB - OBJECTIVE: The aim was to characterise subcellular histochemical evidence of the involvement of peroxidation and peroxidases in myocardial reperfusion injury. The histochemical technique involved the use of 3,3'-diaminobenzidine (DAB), which reacts with peroxides and proteins with peroxidase activity to form an electron dense polymer. METHODS: Isolated rabbit hearts were perfused (Langendorff method) for 30 min with oxygenated physiological saline solution. Some were subjected to 30 min of normothermic global ischaemia, with or without 30 min reperfusion. Non ischaemic control hearts were perfused continuously for 90 min. Hearts were fixed with glutaraldehyde and cut into 100-150 microns sections that were incubated for 1 h in buffered DAB (1 mg.ml-1) with or without added KCN or H2O2. They were processed further for transmission electron microscopy. Planimetry was done on micrographs taken from random fields (approximately 500 photos). RESULTS: The total amount of DAB polymer in non-ischaemic control heart sections incubated with DAB alone occupied 1.19(SEM 0.44) micron 2 x 1000 micron-2 total cell area. For ischaemic-nonreperfused hearts, the value was 2.32(0.90) micron 2 x 1000 micron-2 (p = 0.223 v control); DAB occupied 7.49(1.42) micron 2 x 1000 micron-2 in ischaemic-reperfused hearts (p = 0.001 v control). DAB positive staining of mitochondria and lipid droplets, but not of peroxisomes, was significantly increased in reperfused hearts compared with non-ischaemic controls. CONCLUSIONS: Reperfusion, but not ischaemia, was associated with increased DAB staining. This suggests a reperfusion induced increase in myocyte peroxidation. Increased staining may be due to the actions of haem proteins with peroxidase activity on peroxidized lipid. PMID- 8490937 TI - Transcardiac alteration of neutrophil function relates to myocardial ischaemia/reperfusion injury. AB - OBJECTIVE: The aim was to define the relation between transcardiac changes in neutrophil function in myocardial ischaemia and the progression of myocardial necrosis. METHODS: Samples of blood from carotid artery, jugular vein, and cardiac vein streaming from the ischaemic area were taken simultaneously in a canine coronary occlusion-reperfusion model of myocardial infarction. Neutrophil function was evaluated by neutrophil count, whole blood chemiluminescence and leucocyte infiltration into the ischaemic myocardium. Myocardial necrosis was assessed by plasma creatine kinase and dual staining technique using Evans blue dye and triphenyltetrazolium chloride. Effects of a free radical scavenger, N-2 mercaptopropionyl glycine (MPG), initiated 15 min before reperfusion and continued during the reperfusion phase, were also examined. RESULTS: Whole blood chemiluminescence of the cardiac vein was reduced at 90 min after coronary artery occlusion as compared to carotid artery [5.8(SEM 0.5) v 7.5(0.7) count x 10(3) cell neutrophil-1 x 10 min-1, p < 0.05], and then increased abruptly after reperfusion to peak after 10 min of reperfusion [7.1(0.7) count x 10(3) cell neutrophil-1 x 10 min-1]. The neutrophil count in cardiac venous blood was significantly reduced within 5 min of reperfusion. MPG significantly attenuated the reperfusion associated increase in cardiac vein whole blood chemiluminescence and the decrease in the cardiac venous blood neutrophil count. The increase in myocardial free radical generation 1-3 h after reperfusion, as assessed by the electron paramagnetic resonance spin trapping technique, was reduced markedly, as was the extent of leucocyte infiltration into the ischaemic myocardium. Under these conditions, administration of MPG significantly reduced myocardial infarct size [40.3(4.5)% v 21.4(4.2)%, p < 0.05]. A marked increase in transcardiac creatine kinase release after reperfusion observed in control dogs was also reduced significantly. CONCLUSIONS: A transient alteration of neutrophil function occurs in the coronary circulation immediately after reperfusion, which may augment neutrophil infiltration and free radical generation in the ischaemic myocardium, leading to the propagation of myocardial ischaemia/reperfusion injury. PMID- 8490939 TI - Direct evidence that coronary perfusion affects diastolic myocardial mechanical properties in canine heart. AB - OBJECTIVE: The effect of coronary perfusion on left ventricular chamber distensibility is only indirect evidence that perfusion alters the mechanical properties of the myocardium. The aim of this study was to demonstrate explicitly the effects of coronary perfusion on these mechanical properties. METHODS: The effects of different levels of coronary perfusion were studied both on in-plane stress-strain relations and on transverse stiffness in an isolated, perfused canine interventricular septal preparation. Additionally, to determine the vascular compartment responsible for the mechanical effects of perfusion on tissue properties, we examined the in-plane stress-strain responses and transverse stiffness after embolisation of the vasculature with 15 microns microspheres. RESULTS: The data show a clear dependence of tissue stress-strain properties on perfusion. The in-plane stress-strain relations were shifted to the left and transverse stiffness increased linearly as septal artery perfusion pressure increased. The dependence of both the in-plane stress-strain relations and transverse stiffness on perfusion was significantly decreased following embolisation. CONCLUSIONS: Myocardial tissue stiffness is directly related to perfusion. The linear relationship between transverse stiffness and perfusion makes it easier to assess the effects of perfusion on tissue stiffness than with in-plane stress-strain relations. Perfusion of capillaries and/or venules is largely responsible for these alterations in myocardial stiffness. PMID- 8490938 TI - Effect of prostaglandins I2 (prostacyclin) and F2 alpha on function, energy metabolism, and calcium uptake in ischaemic/reperfused hearts. AB - OBJECTIVE: The aim was to examine the effect on cardiac function, energy metabolism, and calcium uptake of either prostaglandin I2 (PGI2, prostacyclin) or prostaglandin F2 alpha (both 28.6 nM) on the response of isolated rat hearts to 25 min of total global ischaemia with or without 30 min reperfusion. METHODS: Rat hearts were perfused by the Langendorff method and function assessed by left ventricular pressure. Energy metabolites were measured using enzymatic techniques and 45Ca2+ uptake determined by radioisotopic analysis. RESULTS: Although there was no effect of either prostaglandin on contractile depression during ischaemia, both compounds accelerated the onset of and increased the magnitude of ischaemic contracture. High energy phosphate content at the end of the ischaemic period was not affected by prostaglandin treatment; however, tissue lactate levels were increased by PGI2 as was tissue calcium content. Under control conditions mean recovery of left ventricular developed pressure ranged from 66% to 83%. In the presence of PGI2 and PGF2 alpha, recovery of developed pressure was reduced to 20% and 38% of preischaemic values, respectively. The reduced recovery in developed pressure was accompanied by an approximately threefold increase in diastolic pressure (p < 0.05). The depression of functional recovery in reperfused hearts treated with prostaglandins was associated with various disturbances of cellular metabolism including depressed ATP and creatine phosphate content and increased tissue lactate and calcium following 30 min of reperfusion. A significant correlation was found between the changes in developed pressure and diastolic pressure during reperfusion and the reduction in ATP and creatine phosphate repletion. The deficit in recovery of ventricular function also correlated significantly with increased lactate and calcium accumulation in the reperfused heart. CONCLUSIONS: Low concentrations of PGI2 and PGF2 alpha can depress contractile recovery of the globally ischaemic heart through a mechanism associated with altered cellular energy metabolism and increased calcium accumulation. PMID- 8490940 TI - Changes in pulmonary vein flow pattern during volume loading. AB - OBJECTIVE: The aim was to investigate the effect of increased left ventricular filling pressure on the pulmonary vein flow (PVQ) pattern. METHODS: Pulmonary vein flow was recorded using an ultrasonic transit time flow meter in six anaesthetised dogs. Mean left atrial pressure was increased by stepwise volume loading from 7.8(SEM 1.3) to 18.9(1.9) mm Hg (p < 0.01). RESULTS: With loading the PVQ signal developed several characteristic positive and negative waves which corresponded to directionally opposite pressure waves in the left atrium. There was a marked increase in the amplitude of the PVQ signal: peak flow increased from 165(50) to 310(38) ml.min-1 (p < 0.01), while minimum flow decreased from 49(37) to -61(23) ml.min-1 (p < 0.01). The minimum value of PVQ occurred during early ventricular systole, corresponding to the left atrial C wave. With progressive loading there was an increasing deceleration of flow during atrial contraction. To quantify the effect of atrial contraction and the C wave on the flow pattern a ratio was calculated between the integrated flow from the start of atrial contraction to the nadir of the x descent and the integrated flow during the rest of the cardiac cycle. This ratio decreased from 0.40(0.06) to 0.11(0.07) with loading (p < 0.01). In each experiment this flow ratio varied inversely with mean left atrial pressure (regression coefficients between 0.66 and 0.97). CONCLUSIONS: Volume loading caused marked changes in the pulmonary vein flow pattern. The PVQ waves reflected the pressure waves in the left atrium. The relative flow during atrial contraction varied inversely with mean left atrial pressure. Further studies should be done to determine whether this index reflects left ventricular filling pressure under different conditions. PMID- 8490941 TI - Correlated expression of atrial myosin heavy chain and regulatory light chain isoforms with pressure overload hypertrophy in the non-human primate. AB - OBJECTIVE: The aim was to determine the extent to which myosin heavy chain and light chain isoform transitions in atrial myocardium are coordinately regulated under pathological conditions in tissue from normal baboons, hypertensive baboons with myocardial hypertrophy, and baboons in which hypertrophy had regressed. METHODS: Quantitative distributions of myosin heavy chain (MHC) and regulatory myosin light chain (MLC2) isoforms in atrial myocardium from 35 adult baboons were determined by electrophoresis under denaturing conditions and laser densitometry. RESULTS: A significant association was observed between the ratios of MHC and MLC2 isoforms in atrial myocardium (r = 0.73, p < 0.001, n = 69). Expressions of alpha MHC and atrial MLC2 (ALC2) isoforms were correlated in atrial myocardium, as were those of beta MHC and ventricular MLC2 (VLC2) isoforms. In a subset of baboons with experimentally induced renal hypertension (n = 12) both beta MHC and VLC2 isoforms were found at higher levels in left atria than were present in normotensive baboons (p = 0.006, n = 15). Left atria from hypertensive baboons with regressed LVH contained intermediate levels of both beta MHC and VLC2 isoforms. CONCLUSIONS: There is tight coupling between the expression of myosin subunit isoforms under pathological conditions from a primate species closely related to humans. The data suggest that the synthesis of these subunits of myosin may be coordinated at the molecular level. PMID- 8490942 TI - Cardiac angiotensin receptors in experimental hyperthyroidism in dogs. AB - OBJECTIVE: The aim was to define the changes in angiotensin II receptors and the plasma renin-angiotensin system in experimental hyperthyroidism in dogs. METHODS: Hyperthyroidism was induced in dogs by subcutaneous injection of triiodothyronine (T3; 1 mg.kg-1 x d-1 for 14 d; group T); control dogs received saline (group C). Plasma angiotensin II (AII), angiotensinogen, renin activity and concentration, and angiotensin II receptors in left ventricle, right atrium, thoracic aorta, adrenal gland, and liver were measured. RESULTS: T3 treatment caused tachycardia, increased heart weight, hypertrophy of the circumflex and septal coronary arteries, increased plasma renin activity [C = 1.6(SEM 0.2), T = 9.8(2.8) ng angiotensin I.ml-1 x h-1], plasma renin concentration [C = 13.0(3.7), T = 34.5(5.6) ng angiotensin I.ml-1 x h-1], and plasma AII [C = 23(3), T = 104(5) pg.ml-1], while plasma angiotensinogen did not change. There were no significant changes in adrenal gland and right atrial angiotensin II receptor densities; increases were measured in the left ventricle [C = 0.33(0.06), T = 0.75(0.12) pmol.g-1 tissue], thoracic aorta [C = 0.19(0.02), T = 0.28(0.03) pmol.g-1 tissue], and liver [C = 8.4(1.2), T = 12.9(1.7) pmol.g-1 tissue]. The relative affinities of the left ventricular angiotensin II receptor for angiotensin peptides (obtained from displacement assays) were: Sar1, Ile8-AII > AII > angiotensin III > angiotensin I > hexapeptide > pentapeptide. CONCLUSIONS: Experimental hyperthyroidism in dogs results in activation of the plasma renin angiotensin system and up regulation of left ventricular, aortic, and liver angiotensin II receptors. PMID- 8490943 TI - Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat. AB - OBJECTIVE: The aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP). METHODS: Six week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg.kg-1 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis. RESULTS: In the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p < or = 0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups. CONCLUSIONS: Our results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency. PMID- 8490944 TI - Hypoperfusion of the myocardium relative to myocardial metabolism during delayed coronary constriction. AB - OBJECTIVE: The aim was to test the hypothesis that the myocardium becomes hypoperfused, relative to its metabolic demands, during the delayed coronary constriction which is observed following termination of a period of sympathetic stimulation. METHODS: This was tested by beat by beat analysis of the ratio of coronary blood flow to the product of heart rate and systolic blood pressure (HR x SBP), an index of myocardial metabolism, in acutely instrumented open chest canine preparations, before, during, and after direct electrical stimulation of the left stellate ganglion. RESULTS: Myocardial metabolism increased in response to stellate stimulation, as evidenced by increases in heart rate, aortic blood pressure, and HR x SBP. These were accompanied by increased blood flow and decreased vascular resistance in the left anterior descending coronary artery. Delayed coronary constriction, defined as the period with the lowest coronary blood flow observed after the end of the stimulation, occurred 1 to 3 min after stimulation was terminated and was characterised by recovery of heart rate, blood pressure, HR x SBP, and coronary blood flow toward control levels, while coronary vascular resistance overshot to above control levels. The ratio of coronary blood flow to HR x SBP fell progressively in the poststimulation period to significantly less (mean 0.715, range of +/- 1 SEM 0.638 to 0.800, p < 0.05) than control (1.0, by definition) in experiments performed with partial prestenosis of the left anterior descending coronary artery. In a selected subgroup of observations with a mean reduction in coronary blood flow during delayed coronary constriction comparable to that reported previously, the flow/metabolism ratio was even lower (mean 0.239, range of +/- 1 SEM 0.202 to 0.284). CONCLUSIONS: The phenomenon of delayed coronary constriction clearly involves a mismatch between myocardial supply and demand: coronary blood flow becomes inappropriately low for the prevailing level of myocardial metabolism. PMID- 8490945 TI - Skinned cardiac fibres of diabetic rats: contractile activation and effects of 2,3-butanedione monoxime (BDM) and caffeine. AB - OBJECTIVE: The aim was to examine contractile properties of skinned cardiac fibres from rats with streptozotocin induced diabetes and to compare the effects of two agents, caffeine and 2,3-butanedione monoxime (BDM), on myocardial contractile characteristics of normal and diabetic cardiac fibres. METHODS: Small fibre bundles dissected from papillary muscles of the left ventricle were chemically skinned by exposure to Triton X-100. The tension-pCa (pCa = -log10 [Ca2+]) relationships were determined under isometric conditions. RESULTS: In skinned fibres from diabetic rats maximum Ca2+ activated force was unchanged in comparison with normal rats, but a significant, though small, increase in the Ca2+ sensitivity [pCa for one half maximal activation (pCa50)] of contraction was shown. Caffeine (5-20 mM) increased Ca2+ sensitivity in a dose dependent manner and to the same extent in the two groups of preparations. Up to 10 mM caffeine, maximum force was not affected. On the other hand, BDM (2 and 5 mM) decreased Ca2+ sensitivity in both normal and diabetic fibres, but the rightward shift of the tension-pCa relationship induced by BDM was more pronounced in diabetic than in normal fibres: pCa50 was 5.55(SEM 0.02), 5.51(0.01), and 5.46(0.01) in normal fibres, and 5.62(0.01), 5.51(0.02), and 5.45(0.02) in diabetic fibres for 0, 2, and 5 mM BDM, respectively. Maximum tension was similarly decreased by BDM in the two groups of fibres. CONCLUSIONS: (1) No change is induced by diabetes in the site of action of caffeine; (2) some drugs that affect myofilament Ca2+ sensitivity, such as BDM, may act differently in diabetic and control myocardium. PMID- 8490946 TI - Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat. AB - OBJECTIVE: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. METHODS: Isolated rat hearts (n = 10-12 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). RESULTS: The incidence of ischaemia induced ventricular fibrillation was reduced from 70% to 42%, 17% (p < 0.05), and 0% (p < 0.05) in hearts perfused with 0, 0.1, 1.0, and 10.0 microM tacrine. Likewise, the incidence of reperfusion induced ventricular fibrillation was reduced from 100% to 90%, 75%, and 50% (p < 0.05), respectively. Indirect evidence of repolarisation delay by tacrine was provided by QT widening; for example, 15 min after the onset of ischaemia, QT (at 100% repolarisation) was increased from 194(SEM 6) to 231(17), 235(13) (p < 0.05), and 341(24) ms (p < 0.05) by increasing concentrations of drug. QT interval measured in individual hearts during ischaemia correlated inversely with arrhythmia score (r2 = 0.392; p < 0.001). Tacrine had no effect on RR interval, coronary flow, recovery of flow during reperfusion, or occluded zone size. Tacrine caused bradycardia (significant at the 1.0 and 10.0 microM concentrations). In additional hearts (n = 12 per group), reversal of 10.0 microM tacrine-induced sinus bradycardia by left atrial pacing (5 Hz) significantly reduced tacrine induced QT widening (p < 0.05), and increased the incidence of ventricular fibrillation from 0% to 42% (although significant antiarrhythmic and QT widening effects were still present); 10.0 microM tacrine failed to reduce the incidence of reperfusion induced ventricular fibrillation in paced hearts (92% incidence v 100% in controls). CONCLUSIONS: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia). PMID- 8490947 TI - Sympathetic innervation modulates ventricular impulse propagation and repolarisation in the immature rat heart. AB - OBJECTIVE: When cardiac sympathetic innervation in neonatal rats is retarded by antiserum to nerve growth factor, there is a corresponding increase in the QT interval on ECG. Since the propagation of the cardiac impulse and the repolarisation of cardiac cells both contribute to the QT interval, the aim of this study was to determine the role of sympathetic innervation in modulating ventricular impulse propagation and repolarisation. METHODS: Neonatal rats were treated for the first 10 days of life with nerve growth factor (NGF), its antiserum (As), or placebo. Standard microelectrode techniques were used to study the transmembrane action potential characteristics of subendocardial (ventricular septal) and subepicardial ventricular myocardium. Bipolar surface electrograms were used to record the velocity of impulse propagation and electron microscopy to examine the intercalated discs. RESULTS: In the subendocardium, the phase 0 upstroke velocity of the action potential (dV/dtmax) was lowest in the As treated rats. The latter group also showed the slowest conduction velocity. There were no differences in control action potential durations in the endocardium among the three groups, but in the epicardial tissues, action potential duration was longest in the As treated group. Thus the dispersion in action potential duration was smallest in the As treated animals. Electron microscopic studies of the intercalated discs of ventricular myocytes showed significant enhancement of nexal junction formation in NGF treated rats, whereas As treated animals showed a retarded pattern of both nexal and desmosomal junction formation. CONCLUSIONS: The differences in ultrastructure, conduction, and repolarisation seen in As and NGF treated animals may explain the prolonged QT interval seen in the As treated group. PMID- 8490948 TI - Characterisation of plasma and tissue atrial natriuretic factor during development of moderate high output heart failure in the rat. AB - OBJECTIVE: The aims were (1) to characterise plasma and tissue atrial natriuretic factor (ANF) levels, haemodynamic variables, and renal function at different stages of moderate chronic high output heart failure in the rat; and (2) to assess the contribution of the atria and ventricles to plasma ANF levels. METHODS: Plasma and tissue ANF levels, haemodynamics, and renal function were evaluated at 1, 2, 4, 8, and 16 weeks after the development of aorto-caval shunts. Sham operated animals served as controls at identical time points. Male Sprague-Dawley rats weighing 225-275 g were used in all experiments. RESULTS: Mean arterial blood pressure was lower and right atrial pressure was higher in the aorto-caval shunt groups than in sham operated controls at all time periods. Left ventricular end diastolic pressure was increased significantly in aorto caval shunt rats at 1, 2, and 4 weeks when compared with their control counterparts. Plasma COOH terminal and NH2 terminal ANF concentrations were increased significantly in aorto-caval shunt animals. Plasma ANF was positively correlated with right atrial pressure and left ventricular end diastolic pressure in aorto-caval shunt rats but not in sham operated controls. Aorto-caval shunt animals also developed marked cardiac hypertrophy with decreased atrial ANF concentration, but not content, and increased ventricular ANF concentration and content. Despite high plasma ANF concentrations, aorto-caval shunt rats had a lower packed cell volume at all observed periods and reduced urinary sodium excretion and urinary volume at 1 and 2 weeks, with trends to a reduction at 4, 8, and 16 weeks. Body weight was higher in aorto-caval shunt animals at 16 weeks than in sham operated controls. CONCLUSIONS: (1) Chronically increased cardiac filling pressure stimulated not only ANF release but also ANF synthesis in each cardiac chamber, which in turn contributed to raised plasma ANF concentrations in aorto-caval shunt rats; (2) an attenuated renal response to endogenous ANF and sodium and water retention were apparent in A-C shunt rats. Activation of neurohormonal vasoconstrictor systems and gradually decreased plasma ANF concentrations may contribute to sodium and water retention at different stages of this experimental model of heart failure. PMID- 8490949 TI - Early and late effects of exercise and athletic training on neural mechanisms controlling heart rate. AB - OBJECTIVE: This study addresses the long term and short term effects of heavy dynamic exercise on neural control of heart rate. METHODS: A group of healthy controls was compared with (1) a group of trained athletes during a period of yearly rest (detrained) and (2) a group of trained athletes at the peak of their training routine. Additionally, a group of 10 controls was studied 1, 24, and 48 h after a single bout of maximal dynamic exercise. Spectral analysis of RR interval variability provided markers of sympathetic (low frequency, LF, 0.10 Hz) and vagal (high frequency, HF, 0.25 Hz) modulation of the sinoatrial node. RESULTS: (1) In detrained athletes resting bradycardia was accompanied by a predominant HF rhythmic component suggestive of a prevailing vagal tone. (2) Trained athletes showed a resting bradycardia together with high LF values, thus suggesting a more complex neural interaction modulating heart rate. An additional longitudinal part of the study, performed on a group of detrained athletes who were examined for the second time after resuming training, confirmed the finding of a prevailing LF component in resting conditions. (3) In the 10 control subjects maximal dynamic exercise induced an increase in LF which outlasted the cessation of exercise up to 24 h, suggesting a persistent sympathetic activation. (4) Passive tilt, a manoeuvre which enhances sympathetic drive, produced a greater enhancement of the LF component in trained athletes than in control subjects. CONCLUSIONS: The cardiac sympathetic excitation outlasting heavy dynamic exercise may explain the coexistence of training bradycardia with signs of enhanced sympathetic activity in trained champion athletes. PMID- 8490950 TI - Diminished neuropeptide Y and dopamine beta-hydroxylase immunoreactivity in a guinea pig model of left ventricular hypertrophy. AB - OBJECTIVE: The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta hydroxylase immunoreactivity. METHODS: Pressure overload was produced in female adult guinea pigs by constriction of the abdominal aorta, using a modified Weck haemoclip. The same operation was performed on a separate group of animals except that no clip was placed around the aorta. Five weeks after surgery, animals were anaesthetised, and the hearts were fixed by perfusion for immunohistochemistry. Cryostat sections were stained, using an indirect peroxidase/antiperoxidase method, for NPY or dopamine beta-hydroxylase. RESULTS: Aortic stenosis caused a 45% increase in left ventricular weight and a 58% increase in left atrial weight at 5 weeks postsurgery. Pulmonary oedema, a sign of cardiac failure, was evident in most of the animals with aortic stenosis. Immunohistochemical studies showed that in atria and right ventricles from animals with abdominal aortic stenosis the distribution and density of NPY-LI nerve fibres were similar to those in the sham operated guinea pigs. However, the left ventricles obtained from the animals with aortic stenosis were nearly devoid of NPY-LI nerve fibres. The density of dopamine beta-hydroxylase-LI nerve fibres was also substantially reduced in the hypertrophied left ventricles. CONCLUSIONS: Aortic stenosis resulting in left ventricular hypertrophy caused a nearly complete loss of NPY-LI and dopamine beta hydroxylase-LI nerve fibres from the left ventricle. The parallel reduction in both neuropeptide Y and dopamine beta-hydroxylase is in accordance with the association of neuropeptide Y with sympathetic (adrenergic) nerve fibres in the left ventricle and suggests that chronic left ventricular hypertrophy causes a severe degeneration of sympathetic axons supplying this chamber and/or reduces the ability of these sympathetic neurones to maintain normal levels of neurotransmitter related enzymes and neuropeptides. PMID- 8490952 TI - Comparative assessment of regional left atrial perfusion by laser Doppler and radionuclide microsphere techniques. AB - OBJECTIVE: The aim was to study the relation between left atrial microcirculatory flux, using laser Doppler flowmetry (LDF), and blood flow, using radiolabelled microspheres (MS). METHODS: Studies were done in five anaesthetised dogs. LDF probes were sewn to the appendage and body of the left atrium. Radionuclide spheres (15 microns) were used to quantitate blood flow at baseline, and during atrial pacing at 3.5 Hz, atrial fibrillation, and intravenous adenosine infusion (1 mg.kg-1 x min-1). RESULTS: In the left atrial body, both MS and LDF perfusion increased significantly during pacing and adenosine infusion; only LDF registered significant increases during atrial fibrillation. In the left atrial appendage, MS flow failed to increase significantly with any intervention and LDF perfusion increased significantly only during atrial fibrillation. There was a significant but weak correlation (r = 0.36, p < 0.05) between LDF and MS when data from all sample sites (n = 40) were compared, but good correlation when only baseline and pacing data were compared (r = 0.72, p = 0.0004, n = 20). In four additional dogs with heart failure [mean left atrial pressure 25.3(SD 7.4) mm Hg] produced by three weeks of rapid right ventricular pacing, flux values at baseline were increased significantly compared to control dogs and the responses registered by LDF to pacing, atrial fibrillation, and adenosine infusion were attenuated markedly. CONCLUSIONS: (1) Microcirculatory flux detected by LDF can identify the direction, and to a lesser extent, the magnitude of changes in regional atrial perfusion; and (2) LDF may be useful in identifying abnormalities of vasodilator reserve that accompany chronic left atrial myocardial dysfunction. PMID- 8490951 TI - Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery. AB - OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor. PMID- 8490953 TI - Effect of hypertrophy induced by pressure overload or volume overload on reperfusion induced arrhythmias in anaesthetised rats. AB - OBJECTIVE: The aim was to determine the effect of myocardial hypertrophy on the incidence and severity of arrhythmias following reperfusion after experimental coronary artery occlusion, and to establish if the effect differed between pressure overload hypertrophy and volume overload hypertrophy. METHODS: The experiments were performed in rats. Pressure overload hypertrophy was induced by aortic banding, and volume overload hypertrophy by perforation of the aortic valve. Four weeks after surgery, coronary artery occlusion and reperfusion experiments were performed. RESULTS: Both pressure and volume overloaded hearts exhibited a similar degree of left ventricular hypertrophy of about 45% weight gain compared to control animals. The total number of ventricular premature beats during reperfusion was not significantly increased in either model of hypertrophy. In contrast to volume overload, the incidence of reperfusion induced ventricular fibrillation was significantly increased in pressure overloaded hearts. Furthermore, there was a significant correlation between number of ventricular premature beats and degree of left ventricular hypertrophy, as well as between duration of ventricular tachycardia and degree of hypertrophy in the pressure overloaded group. Such correlations were not observed in hypertrophy due to volume overload. Neither volume nor pressure overload hypertrophy significantly increased mortality from ventricular fibrillation. CONCLUSIONS: An increase in cardiac mass per se does not necessarily aggravate reperfusion arrhythmias. The susceptibility to arrhythmias in this model seems to be critically dependent on the nature of the stimulus triggering left ventricular hypertrophy. PMID- 8490954 TI - Effects of human recombinant interleukin-1 on electrical properties of guinea pig ventricular cells. AB - OBJECTIVE: To determine whether cytokines alter the electrical properties of heart cells, the effects of human recombinant interleukin-1 beta (IL-1) were examined in excised tissues and dissociated myocytes from guinea pig ventricles. METHODS: In a first series of experiments, transmembrane potentials were recorded from isolated papillary muscles superfused with 1 ng.ml-1 IL-1 in the absence and presence of blockers of arachidonic acid metabolism. Secondly, to examine the ionic mechanisms underlying the response to IL-1, ventricular myocytes were dissociated from collagenase perfused hearts and studied using the whole cell configuration of the patch clamp technique under conditions designed to isolate the L-type Ca2+ current (ICa). RESULTS: In excised papillary muscles, IL-1 significantly prolonged action potential duration (measured at 90% repolarisation) by 24.2(SEM 2.2) ms and effective refractory period by 22.9(2.3) ms (both p < 0.001; n = 44). Other measured variables were not affected. Treatment of muscles with cyclo-oxygenase inhibitors, indomethacin (1 x 10(-5) M) or acetyl salicylic acid (2 x 10(-4) M), abolished the prolongation of action potential duration elicited by IL-1. However, the effects of IL-1 were also blocked by the lipoxygenase inhibitor nordihydroguaiaretic acid (2 x 10(-5) M) or by treating tissues with the leukotriene receptor blocker, ICI198615 (1 x 10(-8) M). In isolated myocytes, 1 ng.ml-1 IL-1 increased ICa density in 44 of 78 cells by 33.6(7.5)% [11.7(0.6) v 14.6(0.7) pA.pF-1; p < 0.001] during voltage steps from -40 to 0 mV. CONCLUSIONS: IL-1 modifies electrical properties of cardiac cells via lipid second messengers generated by cyclo-oxygenase and lipoxygenase pathways. Voltage clamp analyses suggest that these effects are mediated, at least in part, by changes in the conductance of calcium channels. PMID- 8490956 TI - Cholesterol induced lipid accumulation in cardiomyocytes. PMID- 8490955 TI - Regional diastolic dysfunction in postischaemic myocardium in calf: effect of nisoldipine. AB - OBJECTIVE: The aim was to assess the effect of nisoldipine on left ventricular systolic and diastolic function during prolonged myocardial ischaemia. METHODS: The left circumflex coronary artery was ligated for 2 h and reperfused for 4 h in 12 calves. The animals were randomised to a control group (n = 6) or to treatment with 1.25 mg.h-1 intravenous nisoldipine (n = 6) during 2 h of ischaemia. Circulatory support by a ventricular assist device was performed throughout the experiment except for the time of haemodynamic measurements. Regional wall thickening of a normal and an ischaemic left ventricular region was determined using pairs of ultrasonic crystals. Left ventricular pressure was measured by micromanometry. Left ventricular wall thickness and regional wall stiffness at a common preload of 10 mm Hg were calculated using an elastic model with shifting asymptote. RESULTS: Ten animals survived after 6 h. No difference was observed in systolic function between controls and nisoldipine treated animals. Systolic thickening of the ischaemic wall remained depressed 4 h after reperfusion and showed some recovery after dopamine infusion. Ischaemic wall stiffness at a common preload was lower after nisoldipine during ischaemia and reperfusion than in controls. Control wall stiffness remained unchanged during the whole experiment with and without nisoldipine. Diastolic thinning of the ischaemic wall was prevented by nisoldipine during ischaemia and after reperfusion. CONCLUSIONS: Prolonged myocardial ischaemia is associated with increased myocardial stiffness of the ischaemic wall. Mechanical unloading can help to bridge the acute phase but cannot prevent postischaemic diastolic dysfunction of the ischaemic wall. Nisoldipine has a beneficial effect on regional diastolic function during ischaemia and reperfusion by decreasing regional wall stiffness and preventing diastolic thinning of the ischaemic wall. PMID- 8490957 TI - Does HIV-1 Tat induce a change in viral initiation rights? PMID- 8490958 TI - A structural superfamily of growth factors containing a cystine knot motif. PMID- 8490959 TI - Is epimorphin involved in vesicular transport? PMID- 8490960 TI - Reexamination of the properties of epimorphin and its possible roles. PMID- 8490961 TI - Correction: LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. PMID- 8490962 TI - Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. AB - Natural resistance to infection with intracellular parasites is controlled by a dominant gene on mouse chromosome 1, called Bcg, Lsh, or Ity. Bcg affects the capacity of macrophages to destroy ingested intracellular parasites early during infection. We have assembled a 400 kb bacteriophage and cosmid contig within the genomic interval containing Bcg. A search for transcription units by exon amplification identified six novel genes in this contig. RNA expression studies showed that one of them, designated Nramp, was expressed exclusively in macrophage populations from reticuloendothelial organs and in the macrophage line J774A. Nramp encodes an integral membrane protein that has structural homology with known prokaryotic and eukaryotic transport systems, suggesting a macrophage specific membrane transport function. Susceptibility to infection (Bcgs) in 13 Bcgr and Bcgs strains tested is associated with a nonconservative Gly-105 to Asp 105 substitution within predicted transmembrane domain 2 of Nramp. PMID- 8490963 TI - Physical interaction of the retinoblastoma protein with human D cyclins. AB - The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin D1 prevents formation of cyclin D1-pRb complexes while enhancing the biological activity of cyclin D1 assayed in vivo. We conclude that cyclins D1 and D3 interact with pRb in a fashion distinct from cyclins A and E, which can induce pRb hyperphosphorylation, and that cyclin D1 activity may be regulated by its association with pRb. PMID- 8490964 TI - DNA topology and a minimal set of basal factors for transcription by RNA polymerase II. AB - Immunoglobulin heavy chain (IgH) gene transcription in vitro can be reconstituted with a minimal reaction containing only TATA-binding protein (TBP), TFIIB, and RNA polymerase II (pol II) when the template is negatively supercoiled. Transcription from linear DNA templates containing either the IgH or the adenovirus major late promoters (MLPs) requires in addition TFIIF, TFIIE, TFIIH, and a fraction containing TFIIA and TFIIJ. Promoters vary in their activities in the minimal reaction. Initiation at the adenovirus MLP site was not observed in this reaction, even with templates containing negative superhelical density. When only TBP, TFIIB, and pol II were present in the reaction, the more negatively supercoiled the IgH template DNA was, the more active the transcription. It is suggested that the free energy of supercoiling promotes the formation of an open complex for initiation of transcription by the minimal set of transcription factors. PMID- 8490965 TI - Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. AB - CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation-specific manner, suggesting an important function for this domain. We report that a chimeric protein in which the extracellular and transmembrane domains of CD45 are replaced with those of the EGF receptor (EGFR) is able to restore TCR signaling in a CD45-deficient cell. Thus, the cytoplasmic domain of CD45 is necessary and sufficient for TCR signal transduction. Moreover, EGFR ligands functionally inactivate the EGFR-CD45 chimera in a manner that is dependent on dimerization of the chimeric protein. Inactivation of EGFR-CD45 chimera function results in the loss of TCR signaling, indicating that CD45 function is continuously required for TCR-mediated proximal signaling events. These results suggest that ligand-mediated regulation of receptor-PTPases may have mechanistic similarities with receptor tyrosine kinases. PMID- 8490966 TI - Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. AB - Antisera against murine Son of sevenless (Sos) recognize a protein of M(r) 155,000 in rat-1 fibroblasts with specific guanine nucleotide exchange activity toward p21c-Ha-ras. Epidermal growth factor (EGF) receptor coimmunoprecipitates with Sos from EGF-stimulated, but not quiescent, cells. The SH2 and SH3 domain containing "adapter" protein Grb2 is also found in Sos immunoprecipitates in an EGF-inducible manner. In vitro reconstitution shows that Grb2 is required for the binding of activated EGF receptor to Sos. A phosphopeptide corresponding to tyrosine 1068 of the EGF receptor blocks both the assembly of the complex and EGF stimulation of nucleotide exchange on p21ras in a permeabilized cell system. These results suggest that EGF-induced activation of nucleotide exchange on p21ras proceeds through the recruitment of cytosolic Sos to a complex with EGF receptor and Grb2 at the plasma membrane. PMID- 8490967 TI - [Ocular involvement in Lyme disease]. AB - Lyme disease is a tick-born multisystemic disease, caused by the Spirochete Borrelia burgdorferi. We examined and treated a 60-year-old woman, who 6 months after a tick bite had developed bilateral uveitis, with the involvement of the anterior segment, vitreous opacities and retinal vasculitis. The ocular involvement was, besides the skin lesion in the first stage of the disease, the only systemic manifestation of the infection. PMID- 8490968 TI - [Implantation of bifocal intraocular lenses. Initial experience]. AB - Twelve patients with bifocal intraocular lenses (3M, Suncoast and IOLAB) were evaluated. In 4 patients authors were not able to evaluate bifocality because of macular disorders and optic atrophy. In all remaining 8 patients the bifocality was strongly expressed. The main problem is a postoperative ammetropia. Implantation of bifocal lenses is connected with side effects which are not usually seen in implantations of monofocal intraocular lenses. PMID- 8490969 TI - [Bifocal and multifocal intraocular lenses. Review]. PMID- 8490970 TI - [Liquid perfluorocarbons in surgery for lens subluxation]. AB - Liquid perfluocarbons (PFC) with a high specific weight and low viscosity were used to remove dislocated lenses from the vitreous body cavity in four patients. In three patients dislocation of the lens with the firm nucleus into the vitreous body cavity occurred following severe contusion, in one female patient luxation of a posterior chamber lens occurred after implantation. After pars plana vitrectomy the liquid PFC lifted the dislocated lens from the bottom of the eye beyond the pupil and from there the lens was removed by means of a cryoprobe and the posterior chamber artificial lens was removed by means of forceps. Liquid PFC are a simple and sparing tool for removal of lenses with a firm nucleus and of implanted lenses from the vitreous body cavity. They reduce manipulation with instruments inside the vitreous body cavity to a minimum. Their use is the operation of choice. The high price of PFC is outweighed by the minimal risk of surgical and postoperative retinal complications. PMID- 8490971 TI - [Malignant intraocular lymphoma]. AB - A thirty-year-old patient irradiated five years previously on account of a cerebral tumour was admitted for pars plana vitrectomy with the diagnosis of bilateral chronic uveitis and secondary glaucoma. The intraocular inflammation was characterized by corneal precipitates, pseudohypopyon, circulating large cell conglomerates in the anterior chamber and a dense whitish infiltration of the vitreous cavity. Because an intraocular malignant lymphoma was suspected, repeatedly a diagnostic pars plana vitrectomy was performed on the right eye and once on the left eye and bilateral actinotherapy was administered. Only the last cytological examination revealed the presence of lymphoma cells. The course of the disease on the two eyes differed. In the right eye despite repeated actinotherapy and repeated pars plana vitrectomy the disease proceeded by infiltration of the retina and the optic disc. In the left eye after par plana vitrectomy the finding on the ocular fundus was permanently without focal changes. An intraocular malignant lymphoma is usually masked by the picture of chronic uveitis. Careful analysis of the case-history, clinical picture and above all the awareness of this life threatening disease, are decisive for establishment of the correct diagnosis. PMID- 8490972 TI - [Effectiveness of peribulbar anesthesia in anterior eye segment surgery]. AB - The single-injection peribulbar technique was performed in 218 patients prior to cataract surgery with les implantation. Peribulbar regional anesthetic block is an effective method of obtaining anesthesia and akinesia. No one case required a reblock or akinesia to perform the surgery safely. There were no major complication associated with the peribulbar technique (one case had to be postponed due to retrobulbar hemorrhage). PMID- 8490973 TI - [Implantation of intraocular lenses in patients with glaucoma]. AB - The authors evaluate the results of operations of cataract with implantation of an intraocular lens in glaucoma patients operated in 1989-1991 at the ophthalmological clinic of the Masaryk Hospital in Usti n. Labem. The group comprised 57 patients, 64 eyes were operated. In 56 eyes ECCE with implantation of IOL was performed, in seven eyes a combined operation with trabeculectomy and in one instance a secondary implantation. The most frequent complication of operations was rupture of the posterior capsule 5 times (7.8%), possibly with loss of the vitreous body 5 times (7.8%). The most frequent early postoperative complication was a fibrinous reaction in the anterior chamber (31.2%). Vision in all patients before operation was 6/60 or poorer. On discharge it was in 48.4% 0.33 or better, 6 months after operation it was in 68.8% eyes 6/18 or better. The intraocular pressure was compensated before operation in 47 eyes (73.4%), decompensated in 7 eyes (10.9%) which corresponds to the number of combined operations. Antiglaucomatous medication after surgery -3 eyes (4.7%) had more medication, 11 eyes (17.2%) had less medication, 39 eyes (60.9%) had the same amount of medication and 11 eyes (17.2%) were without therapy. PMID- 8490974 TI - [Climate therapy of uveitis in a mountain environment]. AB - Climatotherapy as part of treatment of intraocular inflammatory diseases has a worldwide renaissance due to recent research. The stimulating climate in high mountains leads to induction of defence mechanisms in the organism. In these mechanisms participates in particular the neurovegetative, cardiovascular, thermoregulating and immune system. An important effect of climatotherapy is marked vascularization of tissues and increased ACTH and glucocorticoid secretion, and this along with the immunosuppressive action of light during heliotherapy leads to physiological immunosuppression. This fact is significant in particular in the treatment of uveitis and raises hope of reduced doses of corticoids and immunosuppressive drugs which reduces the risk of undesirable side effects of this treatment. The results of climatotherapy is in many instances a reduced number of relapses of inflammatory diseases, shortening of the period of the acute attack and a milder course of the attack. PMID- 8490975 TI - [Natural development of myopia in indications for scleroplasty surgery]. AB - The authors submit a report on investigation of progressing myopia in children and adults meeting the criteria for indication of scleroplastic surgery. However, the operation was not performed. In children with myopia gravis (5 eyes) the progression of myopia in the course of six years was 1.1 +/- 1.02 D, in children with myopia progressiva (14 eyes) 2.9 +/- 1.4 D/6 years. In adults with myopia gravis (96 eyes) the progression in 6 years was 1.5 +/- 1.9 D, in adults with myopia progressiva (7 eyes) the progression in 6 years was 1.1 +/- 1.2 D. The difference in the two groups was statistically significant at the 1% level. It is necessary to seek procedures to prevent progression of myopia to higher values. PMID- 8490976 TI - Lymphatic filariasis: diagnosis and pathogenesis. WHO expert committee on filariasis. AB - In the past few years, knowledge of many aspects of lymphatic filariasis, s debilitating disease with serious economic and social consequences, has increased. This article presents sections on diagnosis, pathogenesis, immunopathology and protective immunity from the recently published Expert Committee's report. PMID- 8490977 TI - Use of a simple anthropometric measurement to predict birth weight. WHO Collaborative Study of Birth Weight Surrogates. AB - Low-birth-weight babies are most at risk of infant mortality. Unfortunately, in many developing countries it is not possible to weigh babies accurately because of the lack of robust scales. This article describes the results of a WHO Collaborative Study to investigate whether birth weight can be predicted accurately using chest circumference and/or arm circumference. The implications of the results for paediatric practice in developing countries are discussed. PMID- 8490978 TI - Computer literature searches on dengue. AB - Many research workers, to save time, rely entirely on either on-line or off-line databases offered by an increasing number of information services. The characteristics of eight databases, including five on-line services, were analysed in the present study concerning the retrieval of information on dengue, the most important mosquito-borne viral disease of humans. Differences in the rate of retrieval among data-bases were apparent, depending on the main subject of publication as well as on the geographical location of the publisher. While rates of retrieval of references in molecular biology were generally satisfactory (mostly > 70%), those in clinical medicine and epidemiology were not (< 50%). The latter, as published in many dengue-endemic tropical countries, were found to be inadequately covered. For the global surveillance of dengue, which has increased in intensity and spread to many countries because of increased international travel, the development of a new database emphasizing tropical geographic medicine is highly desirable. PMID- 8490979 TI - [Yellow fever epidemic in the extreme North of Cameroon in 1990: first yellow fever virus isolation in Cameroon]. AB - Some two years ago, suspicious cases of yellow fever (YF) were reported in northern Cameroon. A deadly epidemic broke out during the second half of the rainy season (from 15 September to 22 December 1990) with 180 known cases, of which 125 died. The real figures could have been between 5000 and 20,000 cases with between 500 and 1000 deaths. The affected area was within the yellow fever belt, which is situated around latitude 11 degrees North and 14 degrees East. In this mountainous area (altitude, about 800 m) the rural inhabitants are scattered, with a high density of 200,000 people per 1000 km2. Investigations began at the start of the dry season and a strain of yellow fever virus was isolated for the first time in Cameroon. A study of 107 serum samples (23 families in 11 villages) was carried out by immunofluorescence and ELISA, which showed 20% IgM carriers for yellow fever virus and nothing for the three other flaviviruses, although these were largely present; there were up to 98% crossed reactions in IgG with dengue 2 and West Nile strains. The under-10 age group represented 63% of the IgM carriers. An entomological study was carried out at the same time. It permitted the capture of Aedes aegypti, A. furcifer, A. luteocephalus and the identification of numerous potential larval sites, at times still in the productive phase of A. aegypti which is considered to be the principal vector.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490980 TI - Influenza surveillance in Pune, India, 1978-90. AB - Continuous surveillance of influenza was carried out in Pune between 1978 and 1990. Most of the cases were identified during investigation of 16 outbreaks of influenza in Pune over this period. The majority of cases were children. Ten of the outbreaks occurred during rainy seasons. A total of 290 isolates consisting of several antigenic variants of influenza type A (H3N2), type A (H1N1), and type B viruses were isolated from throat/nasal swabs that were processed in chick embryos and MDCK cell culture and identified using the haemagglutination inhibition test. These variants circulated every year or in alternate years. Nearly two-thirds of the influenza virus isolates (181 out of 290) were from children aged < 10 years. Seasonal analysis indicated that the highest number of isolates (174) were collected during the rainy months of July, August and September, with the maximum number (93) in July. PMID- 8490982 TI - The seventh pandemic of cholera in the USSR, 1961-89. AB - Over the period 1961-89 a total of 1,713,057 cases of cholera were reported to WHO from 117 countries in all continents. The course of the epidemic fell into three periods: in period I (1961 to 1969), 24 countries (predominantly in Asia) reported about 419,968 cholera cases; in period II (1970 to 1977), 73 countries from Asia, Africa, Europe, and the Americas reported 706,261 cases; and in period III (1978 to 1989), 83 countries reported 586,828 cases. The global epidemic was at its most severe in 1967-74. Subsequently morbidity declined and up to 1989 had remained high and stable, with 44,000-52,000 cases per annum. In the USSR 10,723 cholera cases and carriers were reported between 1965 and 1989 from 11 republics (but not Latvia, Lithuania, Estonia, or Armenia). In 1965 and 1970-74 large-scale outbreaks of imported cholera were characteristic of the epidemic in the USSR. Thereafter morbidity declined, and sporadic cases were reported along with environmental, predominantly nontoxigenic strains of cholera vibrio. Most of the outbreaks in the 1970s were waterborne, and virulent strains containing the vct gene were isolated from samples of water. Large-scale outbreaks continued that were associated with seafood and dairy produce that were contaminated with cholera vibrio. Clinical cases of cholera as well as a considerable number of carriers of avirulent nontoxigenic strains were reported. The epidemiological situation in the USSR is unstable, with cases of cholera and virulent strains from surface water being reported every year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490981 TI - Antibiotic therapy for bacterial meningitis in children in developing countries. AB - We carried out a study to investigate the effectiveness of chloramphenicol alone as a treatment for bacterial meningitis. A total of 70 consecutive children aged > 3 months with bacterial meningitis, who had been admitted to the paediatric hospital of the All India Institute of Medical Sciences, were randomized to receive chloramphenicol alone or chloramphenicol + penicillin. The two groups were matched with each other. Treatment failure occurred with three (9%) patients in the chloramphenicol-alone group and with four (12.1%) patients in the combination therapy group (P > 0.05). The mean duration of intravenous therapy, the number of intravenous cannulae used per patient, and the incidence of thrombophlebitis were significantly higher for the group that received the combination therapy. Also, the cost of using chloramphenicol + penicillin was four times higher than that of chloramphenicol alone. Hence, chloramphenicol alone was as effective as chloramphenicol + penicillin and much cheaper and more convenient to use. PMID- 8490983 TI - A 13-year follow-up of treatment and snail control in an area endemic for Schistosoma mansoni in Brazil: incidence of infection and reinfection. AB - The incidences of Schistosoma mansoni infection and reinfection were investigated in an endemic area of Brazil (Peri-Peri, State of Minas Gerais) where chemotherapy and snail control had been used for 13 years (1974-87). Two cohorts were followed: the first consisted of 584 individuals with no evidence of infection at entry (infection cohort), and the second comprised 296 individuals who were treated and did not eliminate eggs 8-12 months afterwards (reinfection cohort). The incidence of infection (per 100 person-years) decreased from 7.5 in 1974-77 to 3.6 in 1986-87, and that of reinfection from 21.3 in 1974-77 to 3.7 in 1986-87. Calendar period, age at risk, and sex were independently associated with both infection and reinfection, while a heavy S. mansoni egg count prior to treatment (> or = 500 epg (eggs per gram of stools)) was independently associated with reinfection. The geometric mean number of eggs after treatment among those reinfected (47 epg) was approximately half that among those infected for the first time (81.5 epg). Age at risk had the greatest effect on both infection and reinfection. The rate ratios of infection and reinfection were 3 to 6 times higher among individuals younger than 20 years than among those aged > or = 25 years, even after adjusting for confounders. This suggests the existence of a strong protective effect with increased age (because of biological and/or environmental factors) for both infection and reinfection. PMID- 8490984 TI - Schistosomiasis mansoni in Burundi: progress in its control since 1985. AB - Described is the evolution of the schistosomiasis control programme in Burundi since 1985. A single round of selective population chemotherapy was carried out in the Rusizi Plain and the Bugesera focus from 1985 to 1990. The prevalences and intensities of infection as well as the number of symptomatic cases detected in general health services decreased considerably. Annual sample surveys in the treated areas showed, however, that these improvements were rapidly reversed by reinfection of the demographically changing population. Since repeated selective population chemotherapy was not sustainable in the long term, a primary health care approach was adopted. In areas with good access to basic health services, approximately 10% of all schistosomiasis cases now receive treatment annually through this approach. Yearly selective chemotherapy in primary schools in suburban Bujumbura reduced the prevalence of schistosomal infection among pupils from 23% to 9% over the period 1984-90, and this programme has now been extended to highly endemic areas in Imbo-Sud. Focal snail control produced disappointing results, and emphasis has therefore shifted towards health education and environmental control of transmission. PMID- 8490985 TI - [African human trypanosomiasis: study of a scoring system of presumptive diagnosis in the Congo]. AB - A case-control study was carried out in the Congo to define a scoring system based on a number of clinical and epidemiological criteria of African trypanosomiasis due to Trypanosoma brucei gambiense which could be used by peripheral health services to establish a diagnosis. The survey comprised 163 cases and 326 controls. Clinical signs and symptoms were fever, headache, pruritus and skin lesions due to scratching, diarrhoea, oedema, cervical adenopathies, sleep rhythm disturbances, changes in appetite, amenorrhoea or impotence, mental confusion, neurological signs, and other minor clinical disturbances. Other criteria were a history of previous trypanosomiasis and the presence of domestic animals in the home environment. Analysis of the results showed that neither a single criterion nor a group of criteria is pathognomonic for the disease. The selected criteria do not allow discrimination of sleeping sickness patients among suspected individuals who present themselves. A scoring system is therefore of little use at the peripheral level of health services, particularly when considering the additional workload involved. The low diagnostic value of these clinical signs and symptoms and other indicators in African trypanosomiasis stresses the difficulty in developing an early warning tool for an integrated control strategy in primary health care. PMID- 8490986 TI - The marketing of cysticercotic pigs in the Sierra of Peru. The Cysticercosis Working Group in Peru. AB - In Peru pork supplied through regulated slaughterhouses is primarily restricted to the large cities on the coast. Approximately 65% of the pork consumed in the country is obtained through informal channels that are not inspected or supervised. The pathways via which pigs are commercialized were studied in Huancayo, a city in the Peruvian Sierra where cysticercosis is endemic. Official purchase, slaughter, and market records were reviewed. Also, direct surveys and participant observation were carried out at two local live pig markets and at two informal meat markets. Pigs were not processed in local slaughterhouses; instead, they were butchered informally. The proportion of cysticercotic pigs detected by tongue examination ranged from 14% to 25% of the total sold. Since cysticercotic pigs and pork are sold through informal markets, surveys of abattoirs and meat markets are not a reliable way to monitor the prevalence of porcine cysticercosis in Peru. We estimate that 48% of the pork traded informally and 23% of the total pork consumed in Huancayo is derived from pigs that are infected with cysticercosis. PMID- 8490987 TI - Essential drugs and registration of pharmaceuticals: the Sri Lankan experience. AB - Many factors influence the regulation of pharmaceuticals in a country. The essential drugs concept, formulated by the World Health Organization to assist developing countries in selecting appropriate drugs, also provides a basis for regulation. Sri Lanka has long regulated pharmaceuticals as part of its health policy. Over 70% of 3436 pharmaceutical product registrations were found to be drugs (or alternatives) named in the country's essential drugs list. This is despite the fact that product registrations are mainly for the private health care sector, and the list is for the state sector. The essential drugs concept therefore appears to have influenced the pharmaceuticals registered in Sri Lanka. PMID- 8490988 TI - Health, safe water and sanitation: a cross-sectional health production function for central Java, Indonesia. AB - The study describes the development of health production functions and their application in the evaluation of the health impacts of investments in safe water and sanitation. For this purpose, data on the morbidity of waterborne diseases and diarrhoea were collected from medical records in the province of Central Java, Indonesia. A reciprocal production function was found to fit the data best. The health production functions exhibit constant return to scale, i.e., a simultaneous m-fold increase in both safe water and sanitation coverage produces a 1-1/m decrease in morbidity. Safe water was found to be more important for health than the sanitary disposal of excreta. PMID- 8490990 TI - Human listeriosis in 1990. PMID- 8490989 TI - Epidemiology of epilepsy in developing countries. AB - Epilepsy is an important health problem in developing countries, where its prevalence can be up to 57 per 1000 population. This article reviews the epidemiology of epilepsy in developing countries in terms of its incidence, prevalence, seizure type, mortality data, and etiological factors. The prevalence of epilepsy is particularly high in Latin America and in several African countries, notably Liberia, Nigeria, and the United Republic of Tanzania. Parasitic infections, particularly neurocysticercosis, are important etiological factors for epilepsy in many of these countries. Other reasons for the high prevalence include intracranial infections of bacterial or viral origin, perinatal brain damage, head injuries, toxic agents, and hereditary factors. Many of these factors are, however, preventable or modifiable, and the introduction of appropriate measures to achieve this could lead to a substantial decrease in the incidence of epilepsy in developing countries. PMID- 8490991 TI - Regional cerebral blood flow and carbon dioxide reactivity after noncerebral injury in the rat. AB - A loss of cerebral autoregulation and vascular reactivity to CO2 has been reported after a direct head injury; however, little has been published concerning the effect of CO2 after peripheral injury. In the present study, the effects of extracranial injury (bilateral hindlimb ischaemia followed by reperfusion) were studied on regional cerebral blood flow in the hypothalamus and cortex and on the changes in these blood flows induced by altering PaCO2 in the conscious rat. After release of the tourniquets, when fluid was being lost from the circulation into the postischaemic hindlimbs, there was a decrease in regional cerebral blood flow (rCBF). Administration of CO2 at this time markedly increased rCBF. There was no evidence that cerebrovascular responsiveness to hypercapnia was impaired after peripheral injury in the rat. PMID- 8490992 TI - Renal vasodilation with acetylcholine but not secretin increases nonnutrient blood flow. AB - To investigate the fact that, despite its renal vasodilator properties, acetylcholine (ACh) provides no protection against acute renal failure, we measured nutrient (NBF) and nonnutrient renal blood flow (NNBF) during ACh infusion. The effect of ACh and secretin on NBF in the outer and inner cortex and outer medulla using 133Xenon (133Xe) washout with freeze dissection analysis was determined. We then calculated NNBF as the difference between NBF in the entire cortex and outer medulla (133Xe washout) and total renal blood flow (TRBF) measured by electromagnetic flow probe. NNBF was also assessed from the 86Rubidium (86Rb) recovery after administration into the renal artery. ACh increased TRBF without increasing NBF, resulting in an increased calculated NNBF. ACh, but not secretin, increased NNBF in the kidney as measured with 86Rb. Thus we conclude that ACh selectively induces a large increase in NNBF in the kidney. PMID- 8490993 TI - Differential control of sympathetic outflow to kidney, heart, adrenal gland, and liver during systemic hypotension induced by cardiac tamponade in anesthetized dogs. AB - This study was designed to determine if cardiac tamponade-induced hypotension produces differential control in efferent sympathetic nerve activity to the kidney (RNA), heart (CNA), adrenal gland (AdNA), and liver (HNA) in pentobarbital anesthetized dogs and to define whether systemic baroreceptors modify this response. We recorded RNA, CNA, AdNA, and HNA simultaneously during a 10 min period of sustained hypotension of 50 mm Hg, which was produced by intrapericardial saline infusion at 20 ml/min. When blood pressure reached 50 mm Hg, sympathetic nerve activity to all four organs increased significantly. Following this, RNA decreased significantly below the control (72 +/- 12%) at the end of experiment, while CNA, AdNA, and HNA remained elevated above control values throughout the experiment. Renal sympathoinhibition was reversed by cervical vagotomy, whereas this had no effect on CNA, AdNA, and HNA responses to hypotension. Additionally, the combined denervation of vagal, carotid sinus, and aortic nerves did not show any significant change in any variables. Thus these results indicate that hypotension due to cardiac tamponade in dogs produces an initial equivocal sympathoexcitation to the kidney, heart, adrenal gland, and liver followed by vagal afferent-mediated sympathoinhibition to the kidney but sustained excitation to the other three organs. PMID- 8490994 TI - Peripheral opioidergic mechanisms do not mediate naloxone's pressor effect in the conscious rabbit. AB - We tested the hypothesis that the pressor effect of naloxone during acute hemorrhagic hypotension is mediated in part at peripheral sites. Experiments were performed in conscious, chronically prepared rabbits. First, we compared the hemodynamic response to peripheral injections of naloxone and naloxone methobromide during acute hemorrhagic hypotension. Naloxone methobromide, which does not enter the central nervous system, produced a lesser pressor effect than naloxone. Second, we looked for peripheral effects of naloxone after close arterial injection into the hindquarter vasculature. Unlike i.v. injections, close-arterial injection of naloxone did not produce any significant hemodynamic changes during hemorrhagic hypotension. Finally, we compared the capacities of naloxone and naloxone methobromide to block the peripherally mediated cardiovascular response to i.v. methionine-enkephalin in nonhemorrhaged animals. The potency of the two compounds, in terms of their blockade of this peripherally mediated response, was similar. The results of the present study do not support a predominant peripheral role for naloxone during acute hemorrhagic hypotension in conscious rabbits. PMID- 8490995 TI - Induction of group II phospholipase A2 expression and pathogenesis of the sepsis syndrome. AB - Phospholipase A2 catalysed hydrolysis of phospholipid substrates is rate-limiting in the release of arachidonic acid for subsequent downstream metabolism to biologically active eicosanoids. Concomitant release of lysoplatelet activating factor (lyso PAF) serves as the precursor of PAF. Thus, phospholipase A2 (PLA2) is pivotal in the generation of a spectrum of biologically active lipids. Over the course of the past decade, studies have increasingly pointed to a pathogenetic association between endotoxin-induced PLA2 expression and ensuing circulatory shock and multisystem organ failure in animals with experimental endotoxemia as well as in patients with septic shock. The structural, functional, regulatory and biologic characteristics of PLA2 are reviewed in relation to septic shock and its complications and areas of controversy are highlighted. PMID- 8490996 TI - Complement and leukocyte activation in septic baboons. AB - The effect of Escherichia coli infusion on complement and leukocytes was evaluated in a baboon model. During 8 hr, different amounts of live E. coli (5 x 10(8), 2.5 x 10(9) and 10(10) live bacteria kg body weight) were infused. Twenty one baboons were investigated. Activation of complement (terminal C5b-9 complement complex; TCC) and activation of leukocytes (PMN elastase) and plasma concentrations of endotoxin (lipopolysaccharide; LPS) were determined before the start of bacteria infusion and 2, 4, 6, and 8 hr after the start of infusion. In baboons receiving 2.5 x 10(9) and 10(10) live E. coli per kilogram body weight, increasing plasma levels of TCC were found (P < 0.05). No significant alterations of TCC were observed when animals were infused with 5 x 10(8) live E. coli per kilogram body weight during an 8 hr period. Plasma levels of PMN elastase increased significantly in baboons receiving 5 x 10(8), 2.5 x 10(9), and 10(10) live bacteria per kilogram body weight. High levels of LPS were detected in animals receiving 10(10) live E. coli bacteria per kilogram body weight and in animals receiving 5 x 10(8) or 2.5 x 10(9) live E. coli bacteria per kilogram body weight. There was a positive correlation between the formation of TCC and the plasma levels of PMN elastase and LPS and between plasma levels of PMN elastase and of LPS. Activation of complement and leukocytes may contribute to the development of organ dysfunction seen in baboons infused with high amounts of live E. coli. PMID- 8490997 TI - The thyroid and the heart. AB - Cardiovascular manifestations are a frequent finding in hyperthyroid and hypothyroid states. In this review, potential mechanisms by which thyroid hormones may exert their cardiovascular effects and pathophysiological consequences of such effects are briefly discussed. Two major concepts have emerged about how thyroid hormones exert their cardiovascular effects. First, there is increasing evidence that thyroid hormones exert direct effects on the myocardium, which are mediated by stimulation of specific nuclear receptors, which in turn leads to specific mRNAs production. Furthermore, there is some evidence that thyroid hormones may also activate extranuclear sites and may directly alter plasma membrane function. Second, thyroid hormones interact with the sympathetic nervous system by altering responsiveness to sympathetic stimulation presumably by modulating adrenergic receptor function and/or density. Pathophysiological consequences of such direct and indirect thyroid hormone effects include increased myocardial contractility and relaxation that may be related to stimulation by T3 of specific myocardial enzymes. However, when left ventricular hypertrophy occurs in association with hyperthyroidism, it may be related to either direct thyroid hormone-induced stimulation of myocardial protein synthesis or to thyrotoxicosis-induced increases in cardiac work load. Although hyperthyroidism generally has little or no effect on mean arterial blood pressure, hypothyroidism is often associated with increases in diastolic blood pressure that are reversible after hormone substitution and may be mediated in part by sympathetic activation. Moreover, there is increasing evidence that thyroid hormones have direct chronotropic effect on the heart that are independent of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490998 TI - Sudden cardiac death. Support for a role of triggering in causation. AB - Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490999 TI - Regulation of myosin heavy chain genes in the heart. AB - Advances in our knowledge of the regulation of cardiac myosin isoforms made possible by molecular cloning of the alpha- and beta-MHCs genes are reviewed. Expression of these genes in heart does not seem to require MyoD or related proteins of the skeletal muscle myogenic program. Cardiac MHC genes are under the control of T3, which stimulates transcription of the alpha-MHC gene and inhibits beta-MHC mRNA production both in vivo and in cultured heart cells. The responsiveness of the genes to T3 varies in different mammals, however. The genes are most responsive in rat and rabbit, intermediate in sensitivity in calf and subhuman primate (baboon), and very resistant in the dog. The human alpha-MHC gene is T3-inducible in ventricle, but the degree of response has not been quantified. Introduction of chimeric plasmids containing 5' flanking sequences of cardiac MHC genes fused to the CAT gene into cultured heart cells and transgenic animals has permitted identification of regulatory elements. Although the genes are closely linked in genomic DNA, they are controlled independently. The element within the alpha-MHC promoter responsible for induction by T3 is located approximately 160 base pairs from the transcription initiation site. Additional transcriptional activators located 5' upstream amplify the response to T3, probably by looping out intervening DNA sequences. The proximal region of the beta-MHC gene contains important regulatory elements, including those required for repression by T3, muscle-specific expression, a MyoD-independent positive element, and a hormone-independent repressor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491000 TI - The nitrovasodilators. New ideas about old drugs. AB - The nitrovasodilators are a diverse group of pharmacological agents that produce vascular relaxation by releasing nitric oxide. The mechanisms by which these compounds release nitric oxide vary, depending on their chemical structure. Compounds with lower oxidation states of nitrogen such as nitroprusside, nitrosamines, and nitrosothiols release nitric oxide nonenzymatically. In the case of nitroprusside, this involves a one-electron reduction that may occur upon exposure to a variety of reducing agents and tissues such as vascular smooth muscle membranes. In the case of the organic nitrates, which have higher oxidation states of nitrogen, the release of nitric oxide in vascular tissue occurs predominantly by a poorly understood enzymatic process. This interesting property of nitroglycerin is important because it "targets" its effect to vascular tissues that are capable of this enzymatic process. In the case of the coronary circulation, nitroglycerin predominantly dilates the larger coronary arteries while having a minimal effect on coronary resistance vessels < 100 microns in diameter. This prevents the development of coronary steal, which is often encountered with agents that produce intense vasodilation of the coronary resistance vessels. In this review, the mechanisms by which the nitrovasodilators (particularly nitroglycerin) release nitric oxide will be considered, and recent studies of nitroglycerin bioconversion in various-sized coronary vessels will be discussed in detail. PMID- 8491001 TI - Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. AB - BACKGROUND: Patients with essential hypertension have abnormal endothelium dependent vasodilation. Because the endothelium exerts its action on the vascular smooth muscle through the release of several substances, it is important to identify which of these factors is involved in the abnormal response of hypertensive arteries. METHODS AND RESULTS: To investigate the role of endothelium-derived nitric oxide in this abnormality, we studied the vascular effect of the arginine analogue NG-monomethyl-L-arginine, an inhibitor of the endothelial synthesis of nitric oxide, under baseline conditions and during infusion of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, a direct smooth muscle dilator. The study included 11 hypertensive patients (seven men; age, 46.5 +/- 9 years) and 10 normal control subjects (seven men; age, 45.7 +/- 7 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood flow was similar in normal control subjects and hypertensive patients (2.97 +/- 0.7 versus 2.86 +/- 1.1 mL.min-1.100 mL-1, respectively). NG-monomethyl L-arginine produced a significantly greater decrease in blood flow in control subjects than in patients (1.08 +/- 0.6 versus 0.32 +/- 0.4 mL.min-1.100 mL-1; p < 0.004). The vasodilator response to acetylcholine was reduced in patients compared with control subjects (maximum flow, 8.2 +/- 4 versus 16.4 +/- 8 mL.min 1.100 mL-1; p < 0.001). NG-monomethyl-L-arginine blunted the vasodilator response to acetylcholine in control subjects (maximum flow decreased from 16.4 +/- 8 to 7.01 +/- 3 mL.min-1.100 mL-1; p < 0.004); however, the arginine analogue did not significantly alter the response to acetylcholine in hypertensive patients (maximum flow, 8.2 +/- 4 versus 8.01 +/- 5 mL.min-1.100 mL-1). NG-monomethyl-L arginine did not modify the vasodilator response to sodium nitroprusside in either control subjects or patients. CONCLUSIONS: These findings indicate that patients with essential hypertension have a defect in the endothelium-derived nitric oxide system that may at least partly account for both the increased vascular resistance under basal conditions and the impaired response to endothelium-dependent vasodilators. PMID- 8491002 TI - Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension. AB - BACKGROUND: Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endothelium dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of substrate for nitric oxide synthesis. METHODS AND RESULTS: The vascular responses to acetylcholine (an endothelium-dependent vasodilator infused at 7.5, 15, and 30 micrograms/min) and sodium nitroprusside (a direct smooth muscle dilator infused at 0.8, 1.6, and 3.2 micrograms/min) were studied during combined administration of dextrose 5% or L arginine (substrate for nitric oxide synthesis infused at 40 mumol/min) in 12 normal control subjects (seven men and five women; age, 49.3 +/- 7 years) and 14 hypertensive patients (nine men and five women; age, 48.4 +/- 7 years). In addition, the effect of D-arginine (stereoisomer of arginine that is not a precursor of nitric oxide) on the vascular responses to acetylcholine was studied in eight normal control subjects and seven hypertensive patients. Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain gauge plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with normal control subjects (maximum flow, 8.9 +/- 5 versus 15.7 +/- 6 mL.min-1.100 mL-1, respectively; p < 0.007); however, no difference was observed in the response to sodium nitroprusside (11.4 +/- 6 and 11.7 +/- mL.min-1.100 mL-1, respectively). L-Arginine did not significantly change basal blood flow or vascular resistance in either group. In normal control subjects, the infusion of L-arginine significantly augmented the vasodilator response to acetylcholine (maximum flow, 15.7 +/- 6 versus 21.4 +/- 8 mL.min-1.100 mL-1 before and after L arginine, respectively; p < 0.001). In contrast, in hypertensive patients, the infusion of L-arginine did not alter the response to acetylcholine (maximum flow, 8.9 +/- 5 and 8.4 +/- 4 mL.min-1.100 mL-1 before and after L-arginine, respectively). The administration of L-arginine did not modify the response to sodium nitroprusside in either group. Similarly, the infusion of D-arginine did not alter the response to acetylcholine in either group. CONCLUSIONS: In normal humans, availability of substrate for production of nitric oxide is a rate limiting step for endothelium-dependent vascular relaxation. In contrast, increased availability of nitric oxide precursor does not modify endothelium mediated vasodilation in hypertensive patients. These findings provide further evidence of a defect in the endothelium-derived nitric oxide system in hypertension and indicate that this abnormality is not related to decreased availability of substrate for nitric oxide production. PMID- 8491003 TI - Does obesity influence early target organ damage in hypertensive patients? AB - BACKGROUND: Various prospective studies have found that lean hypertensive patients have greater cardiovascular morbidity and mortality than obese hypertensive subjects. It was therefore hypothesized that hypertension is more benign when associated with obesity. In the present study, we evaluated effects of obesity on early target organ damage in patients with essential hypertension. METHODS AND RESULTS: In a total of 207 subjects, systemic and renal hemodynamics as well as left ventricular structure and function were assessed by measuring cardiac output (indocyanine green dye dilution), renal blood flow (clearance of 131I paraimmunohippuric acid), and mean arterial pressure (invasively) and by two dimensionally guided M-mode echocardiographic findings. Systemic and renal vascular resistance, compliance of the large arteries evaluated by the stroke volume/pulse pressure index, and left ventricular mass served as parameters for early target organ damage. All individuals were categorized into four groups: lean and obese normotensive as well as lean and obese hypertensive subjects. In obese hypertensive patients, total peripheral resistance was significantly lower and stroke volume/pulse pressure index was higher than in the lean hypertensive group, almost reaching values of normotensive control subjects. No effect of obesity on the renal circulation was noted, whereas in hypertension, renal vascular resistance was elevated. The degree of left ventricular hypertrophy was more pronounced in the hypertensive groups than in their normotensive counterparts and progressively increased with obesity. Nevertheless, in obese hypertensive patients, left ventricular function, as measured by fractional fiber shortening and velocity of circumferential fiber shortening, was maintained despite the fact that the heart had been exposed to the double burden of an increased preload (obesity) and afterload (hypertension). CONCLUSIONS: Obesity had a disparate effect on target organs in hypertension. At rest, obesity seemed to mitigate cardiovascular changes in the systemic vascular bed caused by hypertension. However, no such mitigation was observed in the renal vasculature, and left ventricular hypertrophy was even exacerbated by the presence of obesity. Our findings in part negate the concept that obesity is able to exert a protective effect on early target organ damage in hypertensive patients and, in particular, on the heart. PMID- 8491004 TI - Time course of restenosis during the first year after emergency coronary stenting. AB - BACKGROUND: Prevention of abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) represents one of the current indications for intracoronary stent implantation. After the procedure, the stented segment undergoes luminal changes that may lead to late restenosis. This study was undertaken to assess the time course of luminal changes during the first year after emergency placement of coronary stents. METHODS AND RESULTS: Coronary stenting was indicated in patients with present or threatened vessel closure secondary to large dissections after PTCA. From June 1989 to May 1991, 82 patients who received Palmaz-Schatz stents and did not have early vessel occlusion after stenting were enrolled into a serial angiographic follow-up study. Coronary normal reference diameter and minimal luminal diameter were measured with an automated edge detection technique. Patients who underwent repeat PTCA for restenosis were excluded from further serial angiography. The restudy rate at 3, 6, and 12 months was 96%, 81%, and 90% of the eligible patients, respectively. The incidence of restenosis (defined as a diameter stenosis > or = 50%) was 22.0% at 3 months, 31.9% at 6 months, and 33.2% at 12 months. Minimal luminal diameter was increased from 0.66 +/- 0.32 mm before to 2.85 +/- 0.43 mm immediately after stenting. It was 0.46 +/- 0.31 mm smaller than the diameter of the maximally inflated balloon during the procedure. The reduction in minimal luminal diameter was 0.80 +/- 0.69 mm (p = 0.0001) for the first 3 months, 0.29 +/- 0.52 mm (p = 0.0001) between 3 and 6 months, and 0.13 +/ 0.32 mm (p = 0.01) for the last 6 months. The percentage of patients who presented a significant change in minimal luminal diameter (defined as > 0.60 mm) declined from 50.6% during the first 3 months and 18.9% between 3 and 6 months to 6.5% for the period between 6 and 12 months. CONCLUSIONS: The incidence and the time course of restenosis after emergency coronary stenting are similar to that reported for conventional PTCA. Coronary lumen dimensions demonstrated a peak change at 3 months and remained mostly stable after the first 6 months. PMID- 8491005 TI - Dobutamine stress echocardiography for assessment of perioperative cardiac risk in patients undergoing major vascular surgery. AB - BACKGROUND: The purpose of this study was to determine the predictive value of dobutamine stress echocardiography for perioperative cardiac events in patients scheduled for elective major noncardiac vascular surgery. METHODS AND RESULTS: Patients (n = 136; mean age, 68 years) unable to exercise underwent a dobutamine stress test before surgery (incremental dobutamine infusion [10-40 micrograms.kg 1.min-1] continued with atropine [0.25-1 mg i.v.] if necessary to achieve 85% of the age-predicted maximal heart rate without symptoms or signs of ischemia). The clinical risk profile was evaluated by Detsky's modification of Goldman's risk factor analysis. Echocardiographic images were evaluated by two observers blinded to the clinical data of the patients, and results of the test were not used for clinical decision making. Technically adequate images were obtained in 134 of 136 patients, one major complication occurred (ventricular fibrillation), and three tests were discontinued prematurely because of side effects. Finally, data from 131 patients were analyzed with univariate and multivariate methods. The dobutamine stress test was positive (new or worsened wall motion abnormality) in 35 of 131 patients. In the postoperative period, five patients died of myocardial infarction, nine patients had unstable angina, and one patient developed pulmonary edema. All patients with cardiac complications (15 patients) had a positive dobutamine stress test. No cardiac events occurred in patients with negative tests. Five patients with a technically inadequate or prematurely stopped test were operated on without complications. By multivariate analysis (logistic regression), only age > 70 years and new wall motion abnormalities during the dobutamine test were significant predictors of perioperative cardiac events. CONCLUSIONS: Dobutamine stress echocardiography is a feasible, safe, and useful method for identifying patients at high or low risk of perioperative cardiac events. The test yields additional information, beyond that provided by clinical variables, in patients who are scheduled for major noncardiac vascular surgery. PMID- 8491006 TI - Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium. AB - BACKGROUND: Even in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial "stunning") or from adaptation to chronic hypoperfusion (myocardial "hibernation"). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral dependent myocardium. METHODS AND RESULTS: Twenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n = 15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n = 26) and after revascularization (n = 12). Transmural myocardial biopsies from the collateral-dependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n = 9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateral-dependent and remote segments. By contrast, in patients with regional dysfunction (n = 17), collateral-dependent segments had lower myocardial blood flow (77 +/- 25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015 versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2, p < 0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral dependent myocardial blood flow increased from 78 +/- 5 to 238 +/- 54 mL.min 1.100 g-1 in three patients with normal wall motion and from 88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with regional dysfunction. There was a significant (r = -0.85, p < 0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005). CONCLUSIONS: In a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation." PMID- 8491007 TI - Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study. AB - BACKGROUND: Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS: Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS: At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients. PMID- 8491008 TI - Systolic left ventricular function after reperfusion therapy for acute myocardial infarction. Analysis of determinants of improvement. The TAMI Study Group. AB - BACKGROUND: Contrast ventriculograms of 542 patients treated with intravenous thrombolytic agents for acute myocardial infarction were examined to define changes in left ventricular ejection fraction and regional wall motion that occur during the first week after reperfusion therapy for acute myocardial infarction and define clinical, acute angiographic and treatment variables related to improvement in global and regional left ventricular function. METHODS AND RESULTS: Intravenous tissue-type plasminogen activator and/or urokinase was administered to 805 patients during acute myocardial infarction. Mean time from symptom onset to thrombolytic therapy was 3 hours (22 patients received therapy within the first hour). Acute and 7-day catheterization were performed. Paired left ventricular ejection fraction and centerline regional wall motion were available in 542 patients (67%). Stepwise, multivariable analysis of clinical, acute angiographic and treatment variables was used to develop two models: One related to improvement in left ventricular ejection fraction, and the second related to improvement in infarct zone regional function. Left ventricular ejection fraction did not change (51.2 +/- 11.1% for acute versus 51.9 +/- 11.0% for 1 week, p = 0.19). Improvement in infarct zone regional function was modest (14%) at 1 week (-2.54 +/- 1.07 standard deviation per chord for acute versus 2.17 +/- 1.24 at 1 week, p < 0.001). Subgroup analysis demonstrated modest improvement in ejection fraction (1.4 +/- 9.5%) and greater improvement in infarct zone function (19%) in patients with successful sustained reperfusion at 1 week. Depressed left ventricular ejection fraction and infarct zone regional wall motion at the acute study were strongly associated with improvement of these parameters at 1 week. Resolution of chest pain before acute catheterization, infarct-related artery flow at acute catheterization, and depressed regional wall motion in the noninfarct zone were associated with improvement in both ejection fraction and regional infarct zone function at 1 week. Notably, the time from the onset of symptoms to initiation of thrombolytic treatment was not related to subsequent improvement in ventricular function. CONCLUSIONS: Dramatic improvement in left ventricular systolic function is not common after thrombolytic therapy for acute myocardial infarction. Improvement in global and regional systolic function is most closely related to acutely depressed ventricular function and successful acute coronary recanalization. Thus, patients with the most myocardium in jeopardy and successful coronary reperfusion demonstrate the greatest improvement in global and infarct zone ventricular function. Overall, the magnitude of this improvement is modest, suggesting that the benefits of coronary reperfusion are not solely related to improvement in systolic left ventricular function. PMID- 8491009 TI - Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis. AB - BACKGROUND: Thrombolysis has become the standard therapeutic approach in patients with acute myocardial infarction. To identify patients who may benefit from early invasive procedures, reliable noninvasive assessment of success or failure of thrombolytic therapy is mandatory. METHODS AND RESULTS: In a prospective study in 63 consecutive patients undergoing thrombolysis for their first myocardial infarction, serial measurements of creatine kinase (CK), its isoenzyme CK-MB, myoglobin, and troponin T were done to determine their value for noninvasive prediction of coronary artery patency. Blood samples were drawn every 15 minutes during the first 90 minutes, every 30 minutes during the first 4 hours, every 4 hours during the first 24 hours, and every 8 hours during the first 72 hours. The perfusion status of the infarct-related artery was assessed angiographically 90 minutes after initiation of thrombolysis. For each marker, time to its peak concentration and its early initial slope (start of thrombolysis to 90 minutes thereafter) were determined. Areas under receiver operator characteristic (ROC) curves were 0.83, 0.76, 0.82, and 0.80 for maxima of CK, CK-MB, myoglobin, and troponin T, respectively (p = NS by univariate Z test). The corresponding values for early slopes of CK, CK-MB, myoglobin, and troponin T were 0.79, 0.82, 0.89, and 0.80 (p = 0.23 for comparison between myoglobin and CK-MB; p = 0.07 between myoglobin and CK). Sensitivity, specificity, and positive and negative predictive values regarding noninvasive prediction of coronary artery patency after 90 minutes were 80%, 82%, 95%, and 61% for time to CK maximum; 91%, 77%, 91%, and 77% for time to myoglobin maximum; 87%, 71%, 89%, and 67% for early CK slope; and 94%, 88%, 94%, and 82% for myoglobin slope, respectively. When myoglobin slope was assessed together with other clinical reperfusion markers (resolution of chest pain or ST segment elevation, occurrence of reperfusion arrhythmias) by logistic regression analysis, only the myoglobin slope was an independent predictor of coronary artery patency (p < 0.0001). CONCLUSIONS: With regard to noninvasive prediction of coronary artery patency after thrombolytic therapy, measurement of the early initial slopes of the serum markers within only 90 minutes after the initiation of therapy is as accurate as the determination of the time to their peak concentration. Compared with the other markers examined, myoglobin appears to have advantages because of its earlier rise, yielding a better negative predictive value and a higher area under the ROC curve for determination of its early initial slopes. PMID- 8491010 TI - A randomized, prospective comparison of anterior and posterior approaches to radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia. AB - BACKGROUND: Two different techniques have been developed for radiofrequency catheter ablation of typical atrioventricular nodal reentry (AVNRT). Lesions made anteriorly near the apex of the triangle of Koch usually eliminate fast pathway function, whereas lesions made posteriorly near the ostium of the coronary sinus selectively affect slow pathway function. The current study compares the safety, efficacy, and electrophysiological effects of these two techniques in a prospective, randomized fashion. METHODS AND RESULTS: Fifty consecutive patients with typical AVNRT were randomly assigned to receive radiofrequency lesions either anteriorly (n = 22) or posteriorly (n = 28). If the initial approach failed to eliminate inducibility of AVNRT after 1 hour or 10 applications of radiofrequency energy, the alternative ablation technique was used. Patients underwent repeat electrophysiological testing 48 hours and 3 months after ablation. The primary success rates of the anterior and posterior techniques were similar (55% versus 68%, p = NS). All of the patients who failed the initial approach were successfully treated by the alternative technique without developing high-grade atrioventricular block. One patient developed right bundle branch block during an anterior lesion, and another patient developed complete atrioventricular block as the result of a posterior lesion. CONCLUSIONS: The posterior approach to radiofrequency catheter modification of the atrioventricular node is as effective as the anterior approach, and both techniques are associated with a low risk of complications. As long as AVNRT persists, it appears safe to cross over from one technique to the other. PMID- 8491011 TI - Ultrasound-assisted cannulation of the internal jugular vein. A prospective comparison to the external landmark-guided technique. AB - BACKGROUND: Central venous access is an essential part of patient management in many clinical settings and is usually achieved with a blinded, external landmark guided technique. The purpose of this study is to evaluate whether an ultrasound technique can improve on the traditional method. METHODS AND RESULTS: We prospectively evaluated an ultrasound-guided method in 302 patients undergoing internal jugular venous cannulation and compared the results with 302 patients in whom an external landmark-guided technique was used. Ultrasound was used exclusively in an additional 626 patients. Cannulation of the internal jugular vein was achieved in all patients (100%) using ultrasound and in 266 patients (88.1%) using the landmark-guided technique (p < 0.001). The vein was entered on the first attempt in 78% of patients using ultrasound and in 38% using the landmark technique (p < 0.001). Average access time (skin to vein) was 9.8 seconds (2-68 seconds) by the ultrasound approach and 44.5 seconds (2-1,000 seconds) by the landmark approach (p < 0.001). Using ultrasound, puncture of the carotid artery occurred in 1.7% of patients, brachial plexus irritation in 0.4%, and hematoma in 0.2%. In the external landmark group, puncture of the carotid artery occurred in 8.3% of patients (p < 0.001), brachial plexus irritation in 1.7% (p < 0.001), and hematoma in 3.3% (p < 0.001). CONCLUSIONS: Ultrasound guided cannulation of the internal jugular vein significantly improves success rate, decreases access time, and reduces complication rate. These results suggest that this technique may be preferred in complicated cases or when access problems are anticipated. PMID- 8491012 TI - Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group. AB - BACKGROUND: Patients with peripheral vascular disease (PVD) undergo a clinical course that can be complicated by cardiovascular events occurring in several areas of the circulation. METHODS AND RESULTS: In the present study we investigated the ability of picotamide, a substance that inhibits platelet thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptors, to reduce cardiovascular complications in PVD patients. The study was double blind and placebo controlled. After a 1-month run-in period, 2,304 patients were randomly allocated to either placebo or picotamide (300 mg t.i.d.) and followed for 18 months. Major and minor events were analyzed. Results of an "intention-to-treat analysis" were that patients on picotamide suffered 45 major events (3.9%) and 77 minor events (6.7%), whereas those taking placebo suffered 52 major (4.5%) and 99 minor events (8.6%). There was borderline statistical difference between the two groups with respect to the sum of the major and minor events (risk reduction, 18.9%; p = 0.056, log-rank test). Results of an "on-treatment" analysis were that patients on picotamide suffered 40 major (3.8%) and 66 minor events (6.3%), whereas those taking placebo suffered 45 major (4.2%) and 95 minor events (8.9%). The sum of both major and minor events was 106 (10.1%) in the picotamide group and 140 (13.1%) in the placebo group. This difference was significant (risk reduction, 23%; p = 0.029, log-rank test). CONCLUSIONS: The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients. The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy. PMID- 8491013 TI - Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy. AB - BACKGROUND: The morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularly the contribution of mitral leaflet length and size. METHODS AND RESULTS: To clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area < 12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area > or = 12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3 +/- 1.0 versus 1.9 +/- 0.7 cm2 for normal-sized valves; p < 0.001) and also had greater systolic excursion of the anterior leaflet (16.2 +/- 4.5 versus 13.3 +/- 3.3 mm, p < 0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum ("typical" SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae ("atypical" SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening. CONCLUSIONS: Patients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening. PMID- 8491014 TI - Regional myocardial blood flow and glucose utilization in symptomatic patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Previous studies suggested the presence of myocardial ischemia in symptomatic patients with hypertrophic cardiomyopathy. Positron emission tomography, a technique that can identify metabolic consequences of ischemia in coronary artery disease, permits the noninvasive measurements of regional myocardial blood flow and glucose metabolism. This new quantitative imaging approach should therefore be suitable for detecting a possible enhancement of glucose utilization in myocardium of patients with hypertrophic cardiomyopathy and thus may help to elucidate the pathomechanism of ischemia in this disease. METHODS AND RESULTS: In 13 symptomatic patients with hypertrophic cardiomyopathy, myocardial blood flow and glucose utilization were measured with intravenous N-13 ammonia and F-18 deoxyglucose at rest and, in four patients, again during supine bicycle exercise. At rest, blood flow was significantly lower in hypertrophied than in normal myocardium (0.78 +/- 0.19 versus 0.99 +/- 0.13 mL.min-1.g-1, p < 0.025), whereas rates of glucose utilization were similar (0.88 +/- 0.31 versus 0.87 +/- 0.35 mumol.min-1.g-1). With exercise, blood flow and glucose utilization failed to increase in hypertrophic and normal segments but became more heterogeneously distributed throughout the left ventricular myocardium. Blood flow-metabolism mismatches indicative of myocardial ischemia were noted in three patients at rest and in three of the four patients during exercise and were due to reduced flow in the presence of maintained glucose uptake. The discordance between flow and glucose metabolism in hypertrophied myocardium was significantly more prominent in younger than in older patients. CONCLUSIONS: Normal or even elevated rates of glucose utilization and the presence of diminished blood flow in hypertrophied relative to normal myocardium suggest the presence of myocardial ischemia in symptomatic hypertrophic cardiomyopathy. The age dependence of blood flow metabolism disparity suggests differences in the underlying pathophysiology or severity of disease. PMID- 8491015 TI - Quantification of left-to-right atrial shunting and defect size after balloon mitral commissurotomy using biplane transesophageal echocardiography, color flow Doppler mapping, and the principle of proximal flow convergence. AB - BACKGROUND: The flow convergence region (FCR), a zone of progressive laminar velocity acceleration, can be imaged by color Doppler proximal to stenotic and regurgitant orifices. Theoretically, FCR proximal to a discrete circular and planar orifice consists of concentric hemispheric shells of equal and accelerating velocities centered at the orifice. According to the continuity principle, flow rate across any of these isovelocity surfaces equals flow rate through the orifice. The aim of this study was to investigate whether these principles could be applied to quantify left-to-right shunting and the size of atrial septal defects after balloon mitral commissurotomy. METHODS AND RESULTS: Biplane transesophageal echocardiography (TEE) with color flow imaging was performed on 36 consecutive patients (mean age, 57 +/- 16 years; range, 14-78 years) immediately before and within 24 hours of balloon (Inoue, n = 33; Mansfield, n = 3) mitral commissurotomy. Left-to-right atrial shunting was detected by TEE in 33 patients (92%) and by oximetry in 11 patients (31%). The radius r of FCR was measured from the first aliasing limit, at a Nyquist velocity reduced to 11 cm/sec by zero-shifting, to the orifice in the atrial septum. FCR was assumed to be hemispherical. Hence, flow rate (Q) was calculated as 2 pi r2 Vr, where Vr is the velocity at a radial distance r. The velocity profile of transatrial flow was assessed by means of high pulse repetition frequency, from which the maximum flow velocity (Vp) and the velocity-time integral (VTI) were obtained. The flow area of the atrial septal defect was calculated as Qm, the maximal flow rate, divided by Vp. Hence, shunt flow was calculated as flow area x VTI x heart rate. FCR was analyzed in two orthogonal planes. Mean Qm (38.1 +/- 26.5 versus 5.3 +/- 2.7 mL/sec), flow area (22.1 +/- 11.2 versus 4.4 +/- 2.0 mm2), and shunt flow (1,590 +/- 1,070 versus 200 +/- 130 mL/min) on transverse plane imaging were all significantly higher in patients with shunts detected by oximetry than in those without. Similar results were obtained from longitudinal plane imaging. Qm correlated well with oximetric shunt flow (r = 0.89-0.94, p < 0.001) and shunt ratio (r = 0.91-0.94, p < 0.001). Flow area correlated closely (r = 0.93-0.94, p < 0.001) with area determined by direct measurement from two dimensional echocardiography. Shunt flow determined by FCR also correlated closely (r = 0.94-0.98, p < 0.001) with that determined by oximetry and that derived from two-dimensional echocardiography and pulsed Doppler (r = 0.96, p < 0.001). CONCLUSIONS: The flow convergence region imaged by TEE color flow mapping provides new and accurate quantitative information on atrial shunt flow and defect size after balloon mitral valvotomy. It is a quick, reliable, and fairly simple method that can be readily incorporated into routine clinical practice. PMID- 8491016 TI - Effect of medical and surgical therapy on aortic dissection evaluated by transesophageal echocardiography. Implications for prognosis and therapy. The European Cooperative Study Group on Echocardiography. AB - BACKGROUND: Aortic dissection still has a poor prognosis despite progress in therapy. Therefore, this prospective follow-up study was designed to determine whether the degree of communication between true and false lumen in relation to the type of dissection, analyzed by transesophageal echocardiography, influences the risk after initiation of medical or surgical therapy. METHODS AND RESULTS: In eight centers, 168 patients (124 men and 44 women) of age range of 23-84 years with proven aortic dissection were examined by transesophageal echocardiography in the acute phase, after start of medical and/or surgical therapy, and during follow-up (0-65 months; mean, 10 months). Analyses were performed prospectively according to a detailed study protocol. Patients were subdivided by transesophageal echocardiography according to a modified DeBakey classification. Type I aortic dissection was found in 35%, type II aortic dissection in 17%, and type III aortic dissection in 48%. Preoperative mortality was 3%, 7%, and 2%, and survival rates were 52%, 69%, and 70%, respectively. Type III aortic dissection could be subdivided into those with communication and antegrade dissection (ca) (50%), with communication and retrograde dissection limited to the descending aorta (cr desc) (10%), with dissection extended to the aortic arch and ascending aorta (cr asc) (27%), and with noncommunicating (nc) aortic dissection (13%). An open false lumen with no thrombus formation was present in types I, II, III ca and III cr asc aortic dissection in 17%, 21%, 39%, and 27% respectively, although it was most pronounced in types III nc and III cr desc (75% and 78%). During follow-up in patients who survived, thrombus was demonstrated in the false lumen in 80% of type I aortic dissection and 81% of types III ca and III cr asc. Open false lumen was seen in type II aortic dissection in 18%. Spontaneous healing was found in 4% with type II and 4% with type III aortic dissection (mainly in patients with type III nc aortic dissection). Patients with fluid extravasation, pleural effusion, pericardial tamponade, and periaortic effusion as well as mediastinal hematoma had a mortality of 52%. Reoperations were necessary in 12 29%, with the highest rate in patients with type III ca aortic dissection. Survival for patients with types III nc and III cr desc aortic dissection was higher than those with types I, II, III ca, and III cr asc. CONCLUSIONS: Preoperative mortality appears to be reduced by transesophageal echocardiography, allowing rapid initiation of treatment. Intraoperative and postoperative mortality in aortic dissection remains high. Risk factors are fluid extravasation and an open false lumen with high communication. Thrombus formation in the false lumen can be regarded as a good prognostic sign. Surgery appears to be only a first step in the treatment of aortic dissection. Second surgery or closure of entry sites based on intraoperative echocardiography may be considered to induce thrombus formation and reduce aortic wall stress. PMID- 8491017 TI - Scintigraphic pattern of regional cardiac sympathetic innervation in patients with familial long QT syndrome using positron emission tomography. AB - BACKGROUND: The purpose of this study was to determine whether scintigraphic evidence of cardiac sympathetic neuronal dysinnervation is present in patients with the familial long QT syndrome. The "sympathetic imbalance" hypothesis for the familial long QT syndrome proposes that the long QT syndrome results from a congenital imbalance of sympathetic innervation of the heart caused by lower-than normal right cardiac sympathetic activity. Although the majority of clinical features of the long QT syndrome can be understood according to this hypothesis, its validity has never been shown. Noninvasive scintigraphic evaluation of the pattern of sympathetic innervation of the heart has recently become possible with catecholamine analogues that can be taken up by sympathetic nerve terminals: radioiodinated metaiodobenzyl guanidine or C-11 hydroxyephedrine (HED). METHODS AND RESULTS: Nine affected patients, each from a separate family with familial long QT syndrome, were enrolled in this study (three men, six women; mean age, 39 +/- 16 years). Scintigraphic evaluation of the pattern of cardiac sympathetic innervation in each patient was performed with HED in conjunction with positron emission tomography. The results of scintigraphic imaging in these patients were compared with those obtained in 14 asymptomatic volunteers. Scintigraphic evaluation demonstrated that HED retention index and HED uptake normalized to blood flow were no different in patients with the familial long QT syndrome than in normal control patients. CONCLUSIONS: Patients with the long QT syndrome have normal cardiac sympathetic innervation as assessed by HED. This finding, although not incompatible with the sympathetic imbalance hypothesis of the long QT syndrome, suggests that if a decrease in right sympathetic activity is present in patients with familial long QT syndrome, it is unlikely to be attributed to an abnormal distribution of cardiac sympathetic nerves. PMID- 8491018 TI - Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty. AB - BACKGROUND: Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty. METHODS AND RESULTS: At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 1: bolus, 0.15 mg/kg; infusion, 0.6 mg.kg-1.hr-1 (54 patients); group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg.kg-1.hr-1 (53 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg.kg-1.hr-1 (44 patients); group 4: bolus, 0.45 mg/kg; infusion, 1.8 mg.kg-1.hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg.kg-1.hr-1 (54 patients). The hirulog infusion was maintained for 4 hours; the primary end point was abrupt vessel closure within 24 hours of the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 11.3% compared with 3.9% in groups 4 and 5 (p = 0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT > 300 seconds. CONCLUSIONS: The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure. PMID- 8491019 TI - Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function. AB - BACKGROUND: Although many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. METHODS AND RESULTS: Twenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201Tl uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201Tl viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p = 0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p < 0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29 +/- 0.07 to 0.41 +/- 0.11, p = 0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27 +/- 0.05 to 0.30 +/- 0.08, p = NS). CONCLUSIONS: In patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution. 201Tl imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery. PMID- 8491020 TI - The cardioprotective effects of ischemic 'preconditioning' are not mediated by adenosine receptors in rat hearts. AB - BACKGROUND: Adenosine receptor activation has been proposed to explain the cardioprotective effect of ischemic preconditioning in rabbit hearts. We tested this hypothesis in a rat model by assessing whether administration of an adenosine antagonist could block the protective effect of preconditioning and whether adenosine is able to reduce infarct size in rat hearts when given before sustained coronary occlusion. METHODS AND RESULTS: We assessed the effects of the adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT) and adenosine on myocardial infarct size and the incidence of ventricular arrhythmias in five groups of rats: control (nonpreconditioned)+vehicle, control+SPT, preconditioned+vehicle, preconditioned+SPT, and control (nonpreconditioned)+adenosine. All rats underwent 90 minutes of coronary artery occlusion followed by 4 hours of reperfusion while preconditioned rats underwent three 3-minute episodes of ischemia, each separated by 5 minutes of reperfusion before sustained occlusion. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, and infarct size was determined by incubation of heart slices in triphenyltetrazolium chloride. In the nonpreconditioned control rats receiving vehicle, myocardial infarct size expressed as a percentage of the area at risk averaged 55.2 +/- 4.8%. Pretreatment with SPT and adenosine had no effect on infarct size (52.2 +/- 3.1% and 52.6 +/- 3.8%, respectively) in the nonpreconditioned control animals compared with the control animals that received vehicle. Both the preconditioned+vehicle (16.4 +/- 4.3%) and the preconditioned+SPT (18.3 +/- 5.2%) groups had a significant reduction in infarct size (p < 0.01 versus control+vehicle, control+SPT, and control+adenosine), with no difference in infarct size between the two preconditioned groups. The incidence of ventricular tachycardia was significantly decreased in both the preconditioned+vehicle (10%, p < 0.05) and the preconditioned+SPT (25.0%, p < 0.05) groups when compared with the control+vehicle (100%), control+SPT (100%), and control+adenosine groups (100%). There was, however, no significant difference in the incidence of ventricular tachycardia between the preconditioned+vehicle and the preconditioned+SPT groups. CONCLUSIONS: Because the adenosine antagonist SPT failed to abolish the cardioprotective effects of preconditioning and intravenous adenosine was unable to protect the hearts, it is unlikely that the mechanism of preconditioning is mediated by adenosine receptors in the rat model. PMID- 8491021 TI - Circus movement atrial flutter in the canine sterile pericarditis model. Cryothermal termination from the epicardial site of the slow zone of the reentrant circuit. AB - BACKGROUND: We have shown that atrial flutter (AF) in dogs with sterile pericarditis is commonly due to a single-loop reentrant circuit in the lower right atrium comprised of a functional or functional/anatomic obstacle and a slow zone of conduction (SZ) between the central obstacle and the atrioventricular (AV) ring. The goals of the present study were 1) to establish that the epicardial SZ is the critical component of circus movement AF and 2) to identify the optimal site within the epicardial SZ at which interruption of circus movement can be accomplished by ablative techniques. METHODS AND RESULTS: We analyzed the atrial activation patterns during epicardial cooling of the SZ with as N2O-cooled probe in eight dogs (five with clockwise [CW] reentrant circuit, one with counterclockwise [CCW] reentrant circuit, and two with both CW and CCW reentrant circuits around the same pathway). In all eight dogs, cooling (-5 to +5 degrees C for 5-20 seconds) the narrow isthmus at the inferoposterior part of the SZ between the central obstacle and the AV ring reversibly terminated the reentrant circuit, whereas cooling outside this area failed to terminate the reentrant circuit. The circus movement was not observed to continue along alternate pathways when conduction in this critical zone was interrupted. Both CW and CCW reentrant circuits could be terminated from the same site within the SZ. Cooling resulted in slowing of conduction in the SZ (55 +/- 15 msec) in both CW and CCW reentrant circuits. Cooling-induced termination of CW reentrant circuits was characteristically associated with oscillations of conduction in the cooled zone of the last three cycles before termination and conduction block occurred within the cooled zone. The last "manifest" reentrant cycle was associated with the longest conduction delay in the cooled zone. However, this delay was not necessarily reflected in the length of the last reentrant cycle because of compensatory acceleration of conduction in the rest of the pathway. On the other hand, in CCW reentrant circuits, conduction block occurred abruptly at the distal border of the SZ and without significant oscillations of conduction. CONCLUSIONS: The present study provides convincing evidence that single-loop circus movement in this model is critically dependent on an obligatory conduction in a SZ in the inferoposterior portion of the free right atrial wall between a functional obstacle and the AV ring. Because the atrial myocardium behaves electrophysiologically as a two-dimensional surface, the results of this study may help to guide the endocardial electrode catheter ablative technique for treatment of clinical AF. PMID- 8491022 TI - Action potential alternans and irregular dynamics in quinidine-intoxicated ventricular muscle cells. Implications for ventricular proarrhythmia. AB - BACKGROUND: Cardiac cells display rate-dependent beat-to-beat variations in action-potential duration (APD), action potential amplitude (APA), and excitability during periodic stimulation. We hypothesized that quinidine causes a marked increase in the variability of APD, APA, and excitability of ventricular cells isolated from quinidine-toxic, arrhythmic ventricles. METHODS AND RESULTS: Action potentials were recorded from right ventricular endocardial tissues (2 x 1 cm, < 2 mm thick) isolated from dogs in which ventricular tachycardia and ventricular fibrillation (VT/VF) were induced with intravenous quinidine (80-100 mg/kg) over a 5-hour period in vivo (n = 7). As the basic cycle length (BCL) of stimulation was progressively shortened, rate-dependent variations in APD and APA occurred. The initial dynamic change was alternans of APD and APA that could be either in or out of phase between two cells. The magnitude of alternans was a function of the BCL and the strength of the stimulation current. At critically short BCLs, irregular APD and APA behavior emerged in the quinidine-intoxicated cells. In control cells (n = 16) isolated from three nontreated dogs, APD and APA remained constant at all BCLs tested (2,000-300 msec). Quinidine increased the slope of the APD restitution curve compared with control. The observed quinidine APD restitution curve was fitted with a biexponential equation, and computer simulation using the fitted restitution curve reproduced the aperiodic APD seen in the quinidine toxic cells during periodic stimulation. Thus, the observed irregular APD behavior was predictable from the restitution curve. CONCLUSIONS: Quinidine toxicity increases the temporal and spatial variability of APD and APA in the ventricle that may promote the initiation of reentrant VT/VF in vivo. The slope of the APD restitution curve provides a method to quantitate inhomogeneities in repolarization time and could be a useful marker for proarrhythmia. PMID- 8491023 TI - Internal cardioversion of atrial fibrillation in sheep. AB - BACKGROUND: The cardioversion efficacy of multiple defibrillation waveforms and electrode systems was compared in a sheep model of atrial fibrillation. METHODS AND RESULTS: Sustained atrial fibrillation could be induced with rapid atrial pacing in 23 (55%) of the animals. This study was performed in four parts. Six sheep with sustained atrial fibrillation were used for data analysis for each part, except in part 4 where five sheep without sustained atrial fibrillation were used. In part 1, four lead systems and four single capacitor truncated exponential defibrillation waveforms (two monophasic and two biphasic) were tested. In part 2, two transvenous lead systems were compared; one was a right-to left system with one electrode located in the right side of the heart and the other electrode located in the left side of the heart, and the other was a totally right-sided system with both electrodes located in the right side of the heart. Eight (four monophasic and four biphasic) waveforms were tested with each lead system. In part 3, eight transvenous lead systems were compared, and two waveforms (one monophasic and one biphasic) were tested with each lead system. For parts 1-3, probability of success curves were determined for each waveform/lead system configuration using an up-down technique with 15 shocks per configuration. In part 4, shocks were synchronized to the QRS and given through two lead configurations during sinus rhythm in 20-V steps starting with 40 and ending with 500 V, and two waveforms were tested with each lead system (one monophasic and one biphasic). Ventricular fibrillation thresholds were determined by giving shocks during the T wave of sinus rhythm. For part 1, the three lead systems that used only intravenous catheter electrodes had significantly lower defibrillation requirements than the catheter-to-chest wall patch system. A 3/3 msec biphasic waveform had significantly lower defibrillation requirements than any of the other three waveforms in part 1. In part 2, the 3/3-msec biphasic waveform with a right-to-left lead system configuration had significantly lower defibrillation requirements than any other waveform lead system combination tested, and for each waveform tested, the right-to-left configuration had significantly lower requirements than the totally right-sided configuration. In part 3, for each waveform the right-to-left configuration had significantly lower voltage and energy requirements than the corresponding totally right-sided configuration. Furthermore, in part 3, waveform/lead configurations that probably generated high potential gradients near the sinoatrial node and near the atrioventricular node resulted in more postshock conduction disturbances. In part 4, there were no episodes of ventricular arrhythmias with shocks synchronized to the QRS. However, with synchronization to the T wave, ventricular fibrillation was induced in all five animals with the minimum tested voltage, which was 40 V. CONCLUSIONS: This acute model yielded sustained atrial fibrillation in approximately 55% of the animals. Cardioversion of atrial fibrillation in sheep is possible with very low energy requirements using transvenous electrode systems (50% successful energy of 1.3 +/- 0.4 J for the 3/3-msec biphasic waveform with a right-to-left lead system). The biphasic waveform had the lowest defibrillation requirements of any waveforms tested, and right-to-left lead systems resulted in lower defibrillation requirements than totally right-sided lead systems. Also, lead systems that probably generated high potential gradients near the sinoatrial and atrioventricular node areas resulted in more frequent episodes of postshock conduction disturbances. Furthermore, synchronization of the shock to the QRS was vital to avoid potentially lethal postshock ventricular arrhythmias... PMID- 8491024 TI - Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs. AB - BACKGROUND: Prior studies in experimental canine models have demonstrated that intravenous cocaine administration causes myocardial depression. The purpose of the present study was to establish the mechanisms of cocaine's actions on myocardial and left ventricular performance after single intravenous bolus doses in conscious, chronically instrumented dogs, in which the full autonomic influences of cocaine would be manifest. METHODS AND RESULTS: In the intact state, cocaine (1 mg/kg) caused a transient decrease in left ventricular dP/dt (baseline; 3,086 +/- 107 mm Hg/sec; 2.5 minutes, 2,649 +/- 114 mm Hg; p < 0.05) followed by a 25 +/- 4% increase in left ventricular dP/dt that peaked at 15 minutes (left ventricular dP/dt, 3,751 +/- 127 mm Hg/sec, p < 0.01) and remained elevated during the 30-minute period of observation. Both the initial depression and the sustained increase in left ventricular contractile response were dose related. The increase in left ventricular dP/dt persisted under circumstances in which the responses were normalized for changes in heart rate and preload that accompanied cocaine administration. The positive inotropic effects were abolished by full autonomic or selective beta-adrenergic blockades. Finally, both cardiac output (baseline, 2,461 +/- 142 min/mL; peak [5 minutes], 3,434 +/- 218 mL/min; p < 0.05) and left ventricular stroke work (baseline, 39 +/- 5 g.m; peak, 49 +/- 6 g.m; p < 0.05) were increased at all times after cocaine administration, suggesting that pump performance was enhanced, despite early reductions in myocardial contractility. Similarly, indexes of early diastolic filling were enhanced despite transient early prolongation in isovolumic relaxation. CONCLUSIONS: Acute intravenous cocaine administration (0.1-2 mg/kg) has a biphasic effect on myocardial and left ventricular function with a transient depression followed by significant sustained increases in left ventricular contractility. The results are in keeping with an early local effect followed by significant adrenergic stimulation, which may be obscured by anesthesia or masked by changes in loading conditions. PMID- 8491025 TI - Reflex sympathoexcitation by cardiac sympathetic afferents during myocardial ischemia. Role of adenosine. AB - BACKGROUND: Stimulation of cardiac sympathetic afferents during myocardial ischemia has been attributed to bradykinin released from the ischemic myocardium. Recent data from human studies suggest that adenosine may serve as this mediator. Our experiments were done to determine whether reflex sympathoexcitatory responses to activation of cardiac sympathetic afferents during myocardial ischemia could be inhibited by blockade of adenosine receptors and augmented by increasing the local concentrations of adenosine in the ischemic myocardium. METHODS AND RESULTS: Experiments were done in 29 anesthetized dogs with bilateral vagotomy and carotid sinus denervation. Activation of cardiac sympathetic afferent fibers was induced by occlusion of the left anterior descending coronary artery (LAD) combined with rapid atrial pacing (pacing rate, 200 beats per minute). LAD occlusion plus rapid atrial pacing increased renal sympathetic nerve activity by 20 +/- 4% before but by only 7 +/- 1% after administration of aminophylline (100 mg i.v.), an adenosine receptor antagonist. In contrast, LAD occlusion during rapid atrial pacing increased renal sympathetic nerve activity by 18 +/- 8% before and 61 +/- 15% after treatment with dipyridamole (0.57 mg/kg i.v.), an inhibitor of adenosine reuptake. In a separate group of dogs, LAD occlusion during rapid atrial pacing increased renal sympathetic nerve activity similarly before and after sham treatment. CONCLUSIONS: These data suggest that adenosine released during myocardial ischemia activates cardiac sympathetic afferents to cause reflex sympathoexcitation. These findings are consistent with observations made in humans that suggest that adenosine is the mediator of the sensation of angina pectoris, which also results from stimulation of cardiac sympathetic afferents. PMID- 8491026 TI - Cardiac tamponade. A clinical or an echocardiographic diagnosis? AB - In most patients, cardiac tamponade should be diagnosed by a clinical examination that shows elevated systemic venous pressure, tachycardia, dyspnea, and paradoxical arterial pulse. Systemic blood pressure may be normal, decreased, or even elevated. The diagnosis is confirmed by echocardiographic demonstration of moderately large or large circumferential pericardial effusion and in most instances, of right atrial compression, abnormal respiratory variation in right and left ventricular dimensions, and in tricuspid and mitral valve flow velocities. Pulsus paradoxus may be absent with left ventricular dysfunction, atrial septal defect, regional tamponade, and positive-pressure breathing. Systemic venous pressure may be normal with localized tamponade of the left atrium or ventricle. Patients with moderately large or large pericardial effusions may have echocardiographic evidence of right atrial compression without clinical signs of elevated venous pressure or pulsus paradoxus. The majority of these patients have mild or moderate tamponade and if not subjected to pericardial drainage, should be observed closely. In some of these patients, when the etiology is known and the disease can be treated effectively with medication, e.g., nonsteroidal anti-inflammatory agents or adrenal corticosteroids in Dressler's syndrome or relapsing pericarditis, pericardial drainage may not be necessary. PMID- 8491027 TI - Arrhythmogenesis and ventricular dysfunction after myocardial infarction. Is anomalous cellular coupling the elusive link? PMID- 8491028 TI - L-arginine in the clinical arena: tool or remedy? PMID- 8491029 TI - Explosive growth of coronary angioplasty. Success story of a less than perfect procedure. PMID- 8491030 TI - Risk stratification for noncardiac surgery. How (and why)? PMID- 8491031 TI - Dysfunction in collateral-dependent myocardium. Hibernation or repetitive stunning? PMID- 8491032 TI - Coronary rethrombosis after successful thrombolysis. PMID- 8491033 TI - Quantitative color Doppler flow mapping. Is flow convergence at the end of the rainbow? PMID- 8491034 TI - Aortic dissection. The last frontier. PMID- 8491036 TI - Coronary heart disease in the elderly. PMID- 8491035 TI - An implantable atrial defibrillator. An impossible dream? PMID- 8491037 TI - Diagnosis and therapy of Kawasaki disease in children. PMID- 8491038 TI - Development of neural connections between visual cortex and transplanted lateral geniculate nucleus in rats. AB - The development of neural connections between transplanted lateral geniculate nucleus (LGN) and host visual cortex (VC) was studied in slice preparations obtained from rat brain in which a fetal (embryonic day 15-17) rat LGN was transplanted to the white matter underlying the VC of a neonate rat (postnatal day 0-1). Placing a fluorescent dye (DiI) in the transplant of the fixed slices revealed that retrogradely labeled cortical cells projecting to the transplant were broadly distributed through layers II to VI at 1 week after transplantation. Three weeks after transplantation, these cells were virtually confined to layer VI. Likewise, anterograde labeling showed that cells in the transplant sent axons up to layer I with a few branches at 1 week after transplantation, while the axons were found to terminate at layer IV with many arborizations at 3 weeks after transplantation. These observations were supported by electrophysiological studies. Analysis of the antidromic responses of the cortical cells to stimulation of the transplant showed that the efferent cells projecting to the transplant were broadly distributed in layers II-VI at 1 week after transplantation, while they were virtually restricted to layer VI at 3 weeks after transplantation. Current source-density analysis of the field potentials and intracellular analysis of the synaptic potentials in the cortical cells demonstrated that geniculocortical connections were broadly established in layers II-VI at 1 week after transplantation, and were localized to layer IV and VI at 3 weeks after transplantation. These results suggest that the development of neural connections between transplanted LGN and host VC is characterized by an initial broad distribution of afferent and efferent connections without laminar specificity, and by later selection of appropriate connections to yield lamina specific connections comparable to those in normal adult VC. PMID- 8491039 TI - Size-related increase in motoneuron number: evidence for late differentiation. AB - The number of motoneurons in the lumbar lateral motor column (LMC) was compared in bullfrogs (Rana catesbeiana) ranging in body length from 2.5 to 19 cm. Large frogs had 36% more motoneurons than small frogs; however, within the caudal third of the LMC, large frogs had over 70% more motoneurons than small frogs. Injection of small frogs with [3H]thymidine every third day for 20-22 weeks gave no evidence of motoneuron birth. Instead, a pool of small, incompletely differentiated (type L) motoneurons appears to be converted into mature (type M) motoneurons as the animal grows. This hypothesis is supported by several lines of evidence: (1) the number of type-M motoneurons varies directly with body size while the number of type-L cells varies inversely; (2) the increase in type-M motoneurons and the decrease in type-L cells are restricted to the same regions of the LMC; and (3) type-L cells exhibited both immunoreactivity to neurofilament antibodies and histochemical evidence of acetylcholinesterase activity, a marker for spinal motoneurons. PMID- 8491040 TI - Sites of plasmalemmal expansion in growth cones. AB - Studies on plasmalemmal expansion in isolated nerve growth cones identified large, clear vesicles characteristically found in growth cones as the plasmalemmal precursor. The present article examines these plasmalemmal precursor vesicles (PPVs) in greater detail in the intact cell. (a) Pulse-chase experiments with the phospholipid precursor, [3H]glycerol, followed by radioautographic analysis show that PPVs in distal neurites and growth cones are labeled prior to equilibration of the label with the plasmalemma. (b) Pulse-chase experiments with lectin-ferritin conjugates demonstrate that PPVs are not endocytotic, that they contain lectin receptors, and that, during growth, patches of lectin receptors appear on the plasmalemma covering PPV clusters. (c) Freeze-fracture studies show that this plasmalemma shares with PPVs a paucity of intramembrane particles. (d) Lectin labeling experiments and freeze-fracture analysis demonstrate, furthermore, that the plasmalemma forms a network of invaginations at the base of PPV clusters. (e) Correlative studies indicate that the refractive 'vacuoles' seen in growth cones by phase-contrast light microscopy correspond to the PPV clusters seen at the ultrastructural level. These results confirm the identity of the plasmalemmal precursor in the intact cell and demonstrate that PPV clusters form distinct, dynamic organelles specialized for plasmalemmal expansion in the growth cone. PMID- 8491041 TI - Functional roles of brain AT1 and AT2 receptors in the central angiotensin II pressor response in conscious young spontaneously hypertensive rats. AB - Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominantly express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 microliters) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 10.0 micrograms), the AT2 receptor ligand PD 123319 (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG-II-induced pressor effects may involve activation of multiple receptor subtypes. PMID- 8491042 TI - Developmental regulation of carbonic anhydrase expression in mouse dorsal root ganglia. AB - The development of proprioceptive neurons in mammalian dorsal root ganglia (DRG) remains poorly documented since few specific markers for these neurons are known. Recent studies suggest that carbonic anhydrase (CA) is a specific marker of this functionally defined neuronal population. The present study was designed to investigate the development of CA staining in sensory neurons. We investigated CA reactivity in mouse lumbar DRGs from embryonic day 13 (E13) to postnatal day 100 (P100) using a modified cytoenzymatic Hansson method. Neuronal CA reactivity was first detected during the perinatal stage (1-3% of DRG neurons) and increased progressively from P0 to P60 when it reached a plateau (about 30-33% of DRG neurons). Statistical morphometric analysis was used to define whether CA staining identifies the same population(s) during development. The results demonstrated that, whatever the stage of development, reactive neuronal cells are included in the well-defined large type A population. The possibility that neuronal CA expression is a reliable marker of the 'functional activity' of the proprioceptive neurons in mammals is discussed. The late development expression of the enzyme (after target innervation) raises the possibility of a regulation of the CA phenotype by neuron-target interactions. PMID- 8491043 TI - Characterization of neuronal cell varieties migrating from the olfactory epithelium during prenatal development in the rat. Immunocytochemical study using antibodies against olfactory marker protein (OMP) and luteinizing hormone releasing hormone (LH-RH). AB - The development of neurons located outside the olfactory epithelium was studied by using antisera against olfactory marker protein (OMP) and luteinizing hormone releasing hormone (LH-RH) in the rat. The study was restricted to the localization of these cells in the nasal cavity and in the region of the olfactory bulb during development. We describe groups of cells that stain positively for OMP located principally on the ventro-lateral aspect of the olfactory bulbs. A comparison is made with the LH-RH-immunoreactive system of cells which predominate on the medial aspect following the known trajectory of the nervus terminalis. OMP-immunoreactive cells appeared along the course of the olfactory fibers when they were first detected at embryonic day 16. These cells became restricted to a small group above the cribriform plate, ventral to the olfactory bulbs that seemed to disappear shortly after birth. It is concluded that these cells, which like the LH-RH cells have most probably migrated from the olfactory placode, represent a group of intervening neurons between the olfactory receptor cells and the olfactory bulb, serving as hints for olfactory axons to reach their targets during prenatal development. PMID- 8491044 TI - Ischemia-induced death of astrocytes and neurons in primary culture: pitfalls in quantifying neuronal cell death. AB - We have demonstrated that both astrocytes and cerebellar granule cell neurons die during an ischemic insult only when there is complete loss of mitochondrial membrane potential. This was determined by comparing the ability of mitochondria to sequester rhodamine 123 with the ability of cells to exclude propidium iodide. We have also demonstrated that in astrocyte cultures cellular LDH loss correlates directly with propidium iodide uptake, i.e. cell death, and inversely with rhodamine 123 uptake. Thus, both LDH loss and rhodamine 123 uptake can be used to quantitatively measure astrocyte cell death in culture; however, this is not the case with neuronal cultures. It was demonstrated that even in highly enriched cerebellar granule cell neuron cultures where astrocytes comprise less than 10% of the total culture protein, approximately 40% of total culture LDH was in the astrocytes. This was also the case with rhodamine 123 sequestration. Caution must therefore be used when using the LDH technique to determine the proportion of neurons that have died in such enriched neuronal cultures. PMID- 8491045 TI - Ornithine decarboxylase is differentially induced by kainic acid during brain development in the rat. AB - The induction of brain ornithine decarboxylase (ODC) as a consequence of systemic kainic acid administration was studied in the hippocampus and the olfactory cortex-amygdala area of 10-day-old rat pups and 30-day-old young rats. In pups, ODC levels were moderately increased (plus 50-80%) 4 h after kainic acid administration, coming back quickly to control levels afterwards. In young rats, instead, ODC levels were dramatically increased by 17-25-fold, 16 h after kainic acid administration and decreased towards basal levels 48-72 h after injection. The present results suggest that the process of excitotoxic ODC induction can be split in two phases: a first phase characterized by moderate induction and essentially linked to the overstimulation of brain circuits and a second phase, during which a dramatic enzyme stimulation is accompanied by the appearance of neurodegenerative pathology. PMID- 8491046 TI - Lupus membranous nephropathy: long-term outcome. AB - The follow-up of 42 patients affected by lupus membranous nephropathy (LMN) is reported and compared with that of 43 patients affected by diffuse proliferative lupus glomerulonephritis (DPGN), who were the object of a previous study. According to the WHO classification, the patients were subdivided into two groups: pure LMN (Va + Vb class) and LMN with superimposed proliferative lesions (Vc + Vd class). Antiphospholipid antibodies (APA) and lupus anticoagulant were tested in 23 subjects. All the patients were treated with corticosteroids, which were associated to cytotoxic drugs in 28 cases. Although a higher number of complete remissions was obtained in patients with pure LMN, the difference between the 2 groups was not significant (7/26 vs 1/16). At 10 years kidney survival was 93% in all LMN patients with no significant differences between the 2 groups. This 10-year kidney survival rate is very similar to that previously observed by us for DPGN (91%). The WHO histological classification and the chronicity index did not identify the patients who reach end-stage renal failure. Eight patients suffered from thrombotic manifestations which were the cause of death in two cases. Fourteen of the 20 patients studied presented echocardiographic abnormalities. A statistically significant association was found between the occurrence of cardiovascular complications and APA levels. The effectiveness of treatment in LMN remains controversial. We suggest, however, that adequate therapy may significantly improve the prognosis of lupus nephritis thus reducing the differences in the outcome of SLE patients having different histological WHO classes. Cardiovascular illness represents a frequent and severe late complication. PMID- 8491047 TI - Increased mRNA expression encoding for medullasin in peripheral blood mononuclear cells from patients with IgA nephropathy. AB - We investigated mRNA expression for medullasin (an inflammatory serine protease in bone marrow cells) in peripheral blood mononuclear cells (PBMC) obtained from 36 patients with primary IgA nephropathy (IgAN), 30 patients with other types of primary glomerular disease, 18 patients with secondary IgA nephritis including lupus nephritis and hepatic glomerulosclerosis and 24 healthy age-matched controls. The majority of patients with IgAN (86%) showed elevated medullasin expression in PBMC, while no medullasin mRNA expression was detected in PBMC obtained from patients with other types of primary glomerular disease, secondary IgA nephritis or normal healthy controls. A positive correlation was noted between mRNA levels and urinary protein excretion. The medullasin mRNA expression in PBMC also correlated with the severity of the histopathologic changes in renal tissue obtained from patients with IgAN. All the patients with severe proteinuria (more than 3.0 g/day) showed strong [more than (++)] medullasin mRNA expression in their PBMC. In addition, all the patients with more than (++) medullasin mRNA expression are grade III or IV histopathological findings. These studies suggest that abnormally regulated medullasin gene expression in PBMC may be associated with the progression of primary IgAN. PMID- 8491048 TI - Long-term outcome following total parathyroidectomy in patients with end-stage renal disease. AB - Long-term follow up (mean 3.8 years), following elective total parathyroidectomy in thirteen patients with end-stage renal disease is described. Nine patients are alive and all except two have measurable levels of intact parathyroid hormone (PTH). One patient is mildly hyperparathyroid with PTH levels of 143 pg/ml (normal 10-65 pg/ml). All patients did well as far as their bone and mineral metabolism were concerned and there were no fractures, bone pain or metastatic soft tissue calcification. Lumbar spine bone mineral density (BMD) increased above the baseline value and femoral neck bone density was significantly greater than a matched control group of non-parathyroidectomized dialysis patients (1.097 +/- 0.140 versus 0.811 +/- 0.148 g/cm2, Z-score 1.98 +/- 1.64 versus -0.79 +/- 1.07, p < 0.001). Two of the nine patients have been transplanted, both have good allograft function and show increases in BMD. We believe that these findings justify the complete removal of all parathyroid tissue for selected patients with chronic renal failure where medical therapy has failed and aluminium bone disease has been excluded. They also raise the possibility that PTH is necessary for bone loss to occur. PMID- 8491049 TI - Response of vasoactive substances to reduction of blood volume during hemodialysis in hypotensive patients. AB - Hypotension is a frequent complication in patients subjected to regular hemodialysis. Insufficient regulation of blood pressure following dialysis with ultrafiltration has been attributed to a lack in hormone activation. To determine whether altered production of vasoactive hormones is involved in the breakdown of blood pressure regulation during hemodialysis (HD), blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), intact immunoreactive parathyroid hormone (iPTH) and arginine vasopressin (AVP) were examined. The relative BV was measured by continuous hemoglobinometry during the HD period of about 240 min. The total decrease in BV at the end of treatment was 23.5 +/- 4.8% of the pretreatment value. Systolic blood pressure (SBP) was 99.6 +/- 23.0 mmHg before dialysis compared with 74.6 +/- 18.8 mmHg at the end of dialysis and heart rate (HR) increased from 76.3 +/- 5.5/min before to 92.0 +/- 10.0/min at the end of dialysis. Despite the wide range of interindividual variance, the hormonal changes indicate that hypotensive patients under HD develop reduced sensitivity of the angiotensin-renin, adrenergic and AVP systems to volumetric stimuli. A paradoxical activation in iPTH and PRA independent Aldo secretions is apparent. PMID- 8491050 TI - Calcium set point progressively worsens in hemodialysis patients despite conventional oral 1-alpha hydroxycholecalciferol supplementation. AB - Calcium set point was measured in 12 patients on chronic hemodialysis. Dialysate calcium concentration was 1.65 mmol/l. Calcium carbonate (CaCO3) was used as the phosphate binder and oral 1-alpha hydroxycholecalciferol (alfacalcidol) was administered in a dose of 0.25-1.0 micrograms/day for 12 months. Comparing base line and post study values, there were no significant changes in ionized calcium (ICa++), intact immunoreactive parathyroid hormone (iPTH), plasma total calcium (TCa++), plasma phosphate (P), alkaline phosphatase (ALP), or aluminum (Al). However, the relative calcium set point significantly worsened (shifted to the right). Three patients developed hypercalcemia (25%) with a total calcium > 2.65 mmol/l. Total bone mineral content (BMC) fell suggesting demineralization. We conclude that this dose of oral alfacalcidol, CaCO3, and a dialysate calcium concentration of 1.65 mmol/l are not sufficient to halt the progression of secondary hyperparathyroidism in chronic hemodialysis patients. Measurement of calcium set point may be the best early measure of failure to prevent worsening of hyperparathyroidism. PMID- 8491051 TI - Kinetics of serum 1,84 iPTH after high dose of calcitriol in uremic patients. AB - The temporal relation between oral administration of calcitriol and the nadir of PTH concentration is important for selecting optimal schedules of administration of calcitriol in the treatment of secondary hyperparathyroidism. To further assess this issue we examined 9 patients with preterminal renal failure (3 females, 6 males; median age 58.0 years, range 47-64, median S-Crea 4.8 mg/dl, range 3.7-6.8) with elevated baseline concentrations of 1,84 iPTH (median 46.0 pmol/l, range 18-100). After ingestion of a single oral dose of 2.0 micrograms calcitriol a transient rise in 1,25(OH)2D3 levels was seen with a peak at 6 h (from 20 pg/ml; 14-52 to 43 pg/ml; 35-102). 1,84 iPTH levels did not significantly change in the first 24 h, but were decreased significantly (p 0.01) 48 h after a single oral dose of calcitriol, the time to reach nadir varying from 24 to 96 hours. The percent decrease wa highest in patients with the highest baseline concentrations of 1,84 iPTH. Median 1,84 iPTH levels continued to remain below baseline at 48 h (25.0 pmol/l), 72 h (24.0 pmol/l) and 96 h (24.0 pmol/l) after oral calcitriol. A modest increase of S-Ca was noted which was not statistically significant. We conclude that 1. a single dose of oral calcitriol causes a delayed but long-lasting decrease of 1,84 iPTH, 2. decreased 1,84 iPTH levels persist despite return of calcitriol concentrations to baseline levels and 3. 1,84 iPTH may remain below baseline for more than 96 h. PMID- 8491052 TI - The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy. AB - We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked. PMID- 8491053 TI - Pulsatile-secretion of parathyroid hormone in patients with chronic renal failure. AB - Peripheral blood concentration of intact PTH is a simple assay very useful in the diagnosis and evolutive control of secondary hyperparathyroidism in patients with chronic renal failure. Episodic secretion of PTH in CRF patients would affect interpretation of single random determinations. To evaluate the secretory pattern of intact PTH we sampled peripheral blood at 6-min intervals for 60 to 90 min from seven normal subjects (group I) and seven patients with chronic renal failure (group II: 4 with normal parathyroid function and 3 with hyperparathyroidism). The resultant time series of serum intact PTH and ionized calcium were assessed by computerized cluster data analysis program. Evaluation of episodic intact PTH pulsatile nature revealed that in group I, 3 out of 7 normal subjects presented 1 maximum and 6 subjects presented at least one minimum. In group II, 3 out of 4 CRF patients with normal parathyroid function presented at least 1 maximum and all four patients at least one minimum. One out of 3 CRF patients with hyperparathyroidism presented 2 maximum and all three at least one minimum. Despite pulsatile character intact PTH levels were maintained all the time within the normal range in control group and in CRF patients with normal parathyroid function. In CRF patients with hyperparathyroidism intact PTH changes were restricted within a level of hyperparathyroidism. Ionized calcium levels in control group remained virtually constant along the period and in CRF group fluctuated widely. Parathyroid hormone is secreted in a pulsatile fashion in normal subjects and in patients with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491054 TI - Comment on: A new morphological classification of urinary erythrocytes by Tomita et al. PMID- 8491055 TI - Use of OKT 3 and cyclosporin A to treat idiopathic focal segmental glomerulosclerosis. PMID- 8491056 TI - Clinical pharmacokinetics of idarubicin. AB - Idarubicin (4-demethoxy-daunorubicin) is a new commercially available anthracycline antibiotic which is more active than daunorubicin, the accepted reference drug, in the treatment of acute myelogenous leukaemia, which generally involves the combination of an anthracycline and cytarabine [corrected]. It is characterised by metabolic transformation into a 13-dihydro derivative, idarubicinol, which is as active as the parent drug in in vitro models. The pharmacokinetics of idarubicin follow a 2- or 3-compartment plasma disappearance with half-life (t1/2) values of 13 min, 2.4h and 16h, clearance approximately 60 L/h/m2 and volume of distribution at steady-state of 1,500 L/m2. Idarubicinol is characterised by a very long elimination t1/2 of 55h. The ratio of metabolite: parent drug area under the plasma concentration-time curve is often > 2 and is even higher after 2 or 3 daily injections of the drug, the normal drug protocol used in induction or consolidation treatments of acute leukaemias. Idarubicin can also be administered orally and the pharmacokinetics are similar to those after intravenous administration, except that the idarubicinol: idarubicin ratio is increased, probably due to a liver first-pass effect. The bioavailability of idarubicin is 20 to 25%, but if the activity of idarubicinol is taken into account, it is effectively about 40%. After idarubicin administration by either route, there is a progressive accumulation of idarubicinol after multiple once daily but not after once-weekly doses. About 10% of the injected dose is recovered in urine as idarubicin and idarubicinol, and only slightly higher proportions are recovered in bile. This suggests that other unidentified metabolites must be excreted by either or by both pathways. PMID- 8491057 TI - Cephalosporin-probenecid drug interactions. AB - The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support. PMID- 8491059 TI - Identification of patients with impaired hepatic drug metabolism using a limited sampling procedure for estimation of phenazone (antipyrine) pharmacokinetic parameters. AB - Phenazone (antipyrine) 1g was given by short intravenous infusion to 62 study participants (10 healthy drug-free volunteers and 52 patients with chronic liver disease). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of phenazone. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 30 patients. When combined with 1 plasma drug concentration from members of the second group, these led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 32 individuals. Total clearance computed by Bayesian estimation was compared with maximal likelihood estimation of this parameter, the classical procedure. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean error was 0.0477 L/h. The precision of the prediction of this parameter (0.155 L/h) remained lower than the interindividual standard deviation (0.765 L/h). This procedure enables the estimation of individual pharmacokinetic parameters for phenazone. In this study, numerous laboratory tests were performed. A highly significant correlation (p < 0.001) was found between phenazone clearance and the prothrombin time, albumin, gamma-globulin, factor V, antithrombin III, fibrinogen and total bilirubin. Discriminant analysis determined that protein, alkaline phosphatase, creatininaemia and gamma-globulin had more significant discriminating power and gave better prognostic results than those seen with the Child-Pugh test. PMID- 8491058 TI - Pharmacokinetic optimisation of tricyclic antidepressant therapy. AB - Pharmacokinetics has greatly contributed to the elucidation of the variability in clinical response to antidepressants in terms of differences in plasma concentrations due to genetic constitution, age, associated diseases and drug interactions. Despite no general agreement, therapeutic and toxic concentrations have been suggested for some tricyclic antidepressants (TCAs) [amitriptyline, nortriptyline, imipramine, desipramine]. Predictive techniques may be implemented on the basis of which starting TCA dosages may be selected to reach more rapidly those concentrations at which efficacy is more probable. Therapeutic drug monitoring may thereafter assist the clinician in refining the individualisation of the dosage regimen. PMID- 8491061 TI - The use of caffeine for enzyme assays: a critical appraisal. PMID- 8491060 TI - Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. AB - Morphine, morphine-6-glucuronide (M6G), morphine-3-glucuronide (M3G) and normorphine were analysed with high performance liquid chromatography in plasma and urine, collected over 72 h after administration of single intravenous 5 mg and oral 20 mg doses of morphine to 7 healthy volunteers. Systemic plasma clearance of morphine was on average 21.1 +/- 3.4 ml/min/kg (1.27 +/- 0.20 L/h/kg), volume of distribution was 2.9 +/- 0.8 L/kg and oral bioavailability was 29.2 +/- 7.2%. Clearance of morphine to form M3G and M6G comprised 57.3% and 10.4%, respectively, and renal clearance comprised 10.9% of total systemic plasma clearance; hence, more than one-fifth of a dose (20.8%) remained as unidentified residual clearance. On the basis of the area under the plasma concentration-time curves determined after oral and intravenous administration, the ratios of M6G:morphine were 3.6 +/- 1.2 and 0.7 +/- 0.3, respectively. The corresponding figures for M3G:morphine were 29.9 +/- 6.8 and 7.7 +/- 1.4. Differences in metabolic ratios between the parenteral and oral routes could be attributed solely to differences in morphine concentrations as evidenced both by plasma concentrations and amounts excreted in urine. An oral:parenteral potency ratio of 1:3 may, thus, be due to differences in circulating amounts of morphine since the proportions of an administered dose found as M6G and M3G after administration by both routes were equal. A major finding was a slowly declining terminal phase of morphine and metabolites that was evident both in plasma and in urinary excretion versus time curves, where the half-lives of morphine, M3G and M6G were 15.1 +/- 6.5 h, 11.2 +/- 2.7 h and 12.9 +/- 4.5 h, respectively. The terminal half-life of normorphine was 23.9 +/- 10.1 h after oral administration. Comparison of oral with intravenous excretion curves showed that a greater part of morphine and metabolites were excreted during the slowly declining phase after the oral dose than the intravenous dose, which is highly suggestive of enterohepatic cycling. The renal clearance of M6G and morphine was seen to exceed creatinine clearance, possibly due to an active secretion process. PMID- 8491062 TI - Crossover studies: a modified analysis with more power. PMID- 8491063 TI - Evaluation of population pharmacokinetics in therapeutic trials. IV. Application to postmarketing surveillance. AB - The feasibility of incorporating blood sampling for population pharmacokinetic analysis into postmarketing surveillance was evaluated. Demographic and drug disposition data, consisting of two blood samples collected at a random time during two different dose intervals, was prospectively collected for 94 psychiatric inpatients (mean age, 48 +/- 13 years) receiving alprazolam. Mixed effect modeling was used to estimate population pharmacokinetic parameters. The mean alprazolam clearance, volume of distribution, and absorption rate constant were 0.05 L/hr/kg, 0.7 L/kg, and 1.1 hr-1, respectively. Clearance was increased by 59% in women, decreased by 26% in patients with multiple organ disease, and decreased by 23% in patients older than 60 years of age. These estimates are similar to those determined from rigorous premarketing clinical trials. Interindividual variability in alprazolam clearance was relatively small (40%) after adjustment for significant patient covariates. Population pharmacokinetic analysis represents a reasonable approach to assessment of pharmacokinetic variability in a large, heterogenous patient population. PMID- 8491064 TI - Altered patterns of drug metabolism in patients with acquired immunodeficiency syndrome. AB - Caffeine was used to assess acetylation status and indexes of oxidative drug metabolism (demethylation, xanthine oxidation, and 8-hydroxylation) in a control group and in three groups of patients infected with human immunodeficiency virus (HIV): patients with acquired immunodeficiency syndrome (AIDS) who had acute illnesses, stable patients with AIDS, and asymptomatic patients infected with HIV. The prevalence of apparent slow acetylation was greater in AIDS patients with acute illnesses compared with control subjects (27 of 29 [93%] versus 18 of 29 [62%]). Indexes of demethylation were decreased and 8-hydroxylation increased in these patients. Xanthine oxidation was the same as that in the control subjects. In the stable AIDS patients, oxidative pathways were altered in a manner similar to that observed in the AIDS patients with acute illnesses, but acetylation was the same as that in the control subjects. In HIV-infected asymptomatic patients, drug metabolism was the same as that in the control subjects. The increased prevalence of apparent slow acetylation and the altered activity of the oxidative pathways in AIDS patients with acute illnesses may partly explain the increased incidence of adverse drug reactions in these patients. PMID- 8491065 TI - Effect of felbamate on carbamazepine and its major metabolites. AB - Felbamate is a novel antiepileptic drug that is now available in the United States. During a previous double-blind, crossover, placebo-controlled safety and efficacy study, concomitant phenytoin concentrations increased, whereas carbamazepine concentrations decreased. We evaluated the effect of felbamate on the concentrations of carbamazepine and of its major metabolites, carbamazepine 10,11-epoxide (epoxide) and carbamazepine-trans-10,11-diol (diol) in 26 patients. After the addition of felbamate, mean epoxide concentrations increased from 1.8 micrograms/ml during placebo or baseline periods to 2.4 micrograms/ml during felbamate treatment (p < 0.05); there was no significant change in diol concentrations. Mean carbamazepine concentrations decreased from 7.5 micrograms/ml during placebo treatment to 6.1 micrograms/ml during felbamate treatment (p < 0.05). Mechanisms that could account for the increase in steady state epoxide concentrations are induction of carbamazepine metabolism to epoxide, inhibition of the conversion of epoxide to diol, or both. PMID- 8491066 TI - Pharmacokinetics of cyclosporine in heart and lung transplant candidates and recipients with cystic fibrosis and Eisenmenger's syndrome. AB - OBJECTIVE: To compare the pharmacokinetics of cyclosporine in patients with either cystic fibrosis or Eisenmenger's syndrome. METHODS: Patients in the study were heart and lung transplant candidates with either cystic fibrosis (n = 6) or Eisenmenger's syndrome (n = 5), as well as patients who received heart and lung transplantation for either cystic fibrosis (n = 13) or Eisenmenger's syndrome (n = 7). This was no experimental pharmacokinetic study in transplant candidates and an exploratory population pharmacokinetic study in transplant recipients. RESULTS: Patients with cystic fibrosis showed higher blood cyclosporine clearance, higher apparent oral clearance, shorter mean residence time, and more erratic absorption. The coefficient of variation of pharmacokinetic parameters was higher in patients with cystic fibrosis. There were no significant differences in metabolite indexes between the two groups of patients after either oral or intravenous administration. A significant negative correlation was found between cyclosporine clearance and hematocrit (r = 0.81 [95% confidence interval, -0.95 to -0.4.1]). Dose-normalized predose blood concentration measurements were lower in patients with cystic fibrosis after transplantation. There was a significant correlation between hematocrit and log dose-normalized cyclosporine concentration (r = 0.40 [95% confidence interval, 0.30 to 0.49]). The total daily dose per 100 ng/ml trough blood concentration required was estimated to be 2.36 times (95% confidence interval, 1.96 to 2.84) higher in patients with cystic fibrosis. CONCLUSIONS: Cyclosporine pharmacokinetics is more variable in patients with cystic fibrosis. The difference in cyclosporine clearance between the two groups is accounted for by differences in binding in blood rather than metabolism. The findings suggest that patients with cystic fibrosis could be conservatively given initial oral doses that are 1.5 times higher than those for patients who receive transplants because of Eisenmenger's syndrome. PMID- 8491067 TI - Subjective and physiologic effects of intravenous buprenorphine in humans. AB - The pharmacologic profile of sublingual and subcutaneous buprenorphine, a partial opioid agonist, indicates it may be useful as a maintenance drug in the treatment of opioid dependence. However, illicit intravenous self-administration suggests that it may have a greater abuse potential by this route of administration. Physiologic and subjective effects of intravenous buprenorphine (0.0, 0.3, 0.6, and 1.2 mg) were determined in a dose-escalation study in six nondependent volunteers with histories of opioid use. Buprenorphine caused miosis and decreased respiratory rate, increased diastolic blood pressure, and transiently increased heart rate. Buprenorphine increased positive responses on a "feel drug" question and scores on scales of "liking," "good effects," euphoria, and apathetic sedation. Physiologic and subjective responses were not consistently dose related, a finding compatible with the pharmacologic profile of a partial agonist. The findings indicate that buprenorphine has substantial potential for abuse when administered intravenously. PMID- 8491068 TI - Hemodynamics, biochemical effects, and pharmacokinetics of the renin inhibitor remikiren in healthy human subjects. AB - INTRODUCTION: Remikiren (Ro 42-5892) is a potent and specific inhibitor of human renin in vitro. Its in vivo action on plasma renin activity (PRA), immunoreactive renin, and blood pressure has been shown in pilot studies in humans. OBJECTIVE: To investigate tolerability, hemodynamic effects, and biochemical effects of remikiren in relation to its pharmacokinetics after single ascending intravenous and oral doses in healthy humans. METHODS: In this double-blind, placebo controlled, two-way crossover (intravenous and oral) study, single ascending doses of 10, 20, 40, 80, 160, and 320 mg (intravenous) and 100, 200, 400, 800, and 1600 mg (oral) were given; six subjects received active drug and three received placebo at each dose level. At regular intervals, blood pressure, heart rate, cardiac output, PRA, immunoreactive renin, and drug plasma levels were determined. RESULTS: The compound was well tolerated except at the 1600 mg oral dose level at which diarrhea occurred in two subjects. At neither dose were there effects on blood pressure, heart rate, or cardiac output relative to placebo. PRA and angiotensin I production rate decreased and immunoreactive renin increased dose dependently after both intravenous and oral administration. The duration of these effects was also dose dependent and was longer than 12 hours with higher doses. Systemic plasma clearance, volume of distribution, and absolute bioavailability of remikiren were in the magnitude of 900 ml/min, 70 L, and below 1%, respectively. The angiotensin I production rate correlated in a sigmoidal way with plasma drug concentrations independent of the route of administration. CONCLUSION: Remikiren is a potent inhibitor of renin in humans with long-lasting effects after both intravenous and oral administration. PMID- 8491069 TI - A placebo-controlled model for assaying systemic analgesics in children. AB - To assess the sore throat pain model in children as an assay for systemic analgesic agents in children under double-blind, placebo-controlled conditions, we conducted a single-dose parallel study that compared 10 mg/kg ibuprofen (n = 39), a new analgesic agent for children, and 15 mg/kg acetaminophen (n = 38), an approved analgesic for children, to placebo (n = 39) in children from 2 to 12 years of age with acute sore throat. At 1/2, 1, 2, 3, 4, 5, and 6 hours (2 hours in the pediatrician's office followed by 4 hours at home), children assessed pain intensity with a pain thermometer and pain relief with a smiley-face scale. The parent and pediatrician assessed pain intensity and change in pain; the parent also provided an overall evaluation at 6 hours. The children rated ibuprofen and acetaminophen as significantly effective compared with placebo (p < 0.05) on both scales at most posttreatment time points and overall. The parent and pediatrician also rated both active medications as significantly different from placebo on both of their scales (p < 0.05) at several time points and overall. On the parent's overall evaluation, ibuprofen was rated as effective compared with placebo (p < 0.05). Both active agents significantly (p < 0.05) reduced oral temperature in children with baseline temperatures > 99 degrees F. No treatment related adverse effects were observed. We conclude that the sore throat pain model is a sensitive assay for identification of the activity of oral analgesic drugs in children and that ibuprofen is an effective analgesic in children. PMID- 8491070 TI - Conference, reports address public-health implications of tuberculosis. PMID- 8491071 TI - American Heart Association updates life support guidelines. PMID- 8491072 TI - Acyclovir should not be used routinely for chickenpox, says pediatrics academy. PMID- 8491073 TI - Atovaquone to be marketed as oral therapy for Pneumocystis carinii pneumonia. PMID- 8491074 TI - Sotalol marketed for life-threatening arrhythmias. PMID- 8491075 TI - Clonidine and breast-feeding. PMID- 8491076 TI - Pharmacologic strategies for managing premenstrual syndrome. AB - The diagnosis and pharmacologic management of premenstrual syndrome (PMS) are reviewed. PMS refers to physical or affective symptoms that appear during the latter half of the menstrual cycle, remit during menses, and affect the woman's relationships or ability to function. Pharmacologic treatments proposed for PMS include (1) hormonal treatments that alter the menstrual cycle, (2) hormonal treatments based on specific proposed etiologies, (3) drugs that affect fluid balance, (4) inhibitors or precursors of prostaglandins, (5) nutritional supplements, (6) psychotropic medications, and (7) nonprescription preparations. The menstrual cycle can be manipulated with transdermal estrogen and cyclic oral progesterone, oral contraceptives, danazol, or gonadotropin-releasing hormone agonists with steroid hormone replacement. Psychological symptoms may be treated with fluoxetine, clomipramine, or alprazolam. Patients may be given a diuretic for fluid retention; bromocriptine, tamoxifen, or danazol for mastodynia; and nonprescription analgesics for headaches. PMS can be managed through (1) a symptom-oriented management approach or (2) modification of the menstrual cycle. Pharmacotherapy should be initiated only after simpler measures have failed, and the medication must be chosen carefully, with the severity of the impairment weighed against adverse effects of the treatment. PMID- 8491077 TI - Heparin and warfarin therapy after acute myocardial infarction. AB - The roles of heparin and warfarin in reducing morbidity and mortality after acute myocardial infarction (AMI) are reviewed. Full-dose i.v. heparin, with or without thrombolytic therapy, is indicated for the prevention of reinfarction and thromboembolism after AMI. Heparin therapy consists of a bolus dose of 5,000 10,000 units, followed by a continuous infusion to maintain the activated partial thromboplastin time at 1.5-2.5 times the control value, and should be continued for 5-10 days in most patients. A longer course of heparin may be appropriate after non-Q-wave AMI. Patients being switched to warfarin should continue to receive heparin until a therapeutic International Normalized Ratio (INR) has been achieved. Warfarin is indicated for the prevention of thromboembolism in patients with anterior-wall AMI and should be given for three months in most cases. Longer term warfarin therapy should be considered for patients with additional risk factors for thromboembolism. Patients with non-Q-wave infarction who are at high risk of reinfarction may also benefit from long-term warfarin therapy. Warfarin should be administered to maintain an INR of 2.0-3.0. Aspirin reduces mortality and reinfarction rates after AMI and should be given indefinitely to all patients who do not have contraindications. Some patients may benefit from the combination of aspirin and warfarin. Ongoing trials should more adequately define the safety and efficacy of heparin and warfarin, as well as aspirin, alone and in combination in post-AMI patients. New anti-thrombotic agents may also prove beneficial. PMID- 8491078 TI - Infusion technology for predicting and detecting infiltration of peripheral intravenous catheter sites in infants. PMID- 8491079 TI - Possible interaction between sertraline and tranylcypromine. PMID- 8491080 TI - Criteria for use of intravenous ciprofloxacin for infections in adult patients. PMID- 8491081 TI - Criteria for use of indomethacin injection in neonates. PMID- 8491082 TI - Adoptive parents' perceptions of, and comfort with, open adoption. AB - Open adoption is becoming a common element of preparation for and ongoing services in infant and special-needs adoptions. This article discusses the results of a recent survey of 1,268 adoptive parents (1,396 adoptions) in California, in which questions were asked concerning openness and ongoing contact with biological parents. Postplacement contact with biological parents was common in this sample, and adoptive parents seemed cautiously comfortable with contact, with some exceptions. PMID- 8491083 TI - Adoption statistics by state. PMID- 8491084 TI - The regulation of hypothalamic corticotropin-releasing factor release: in vitro studies. AB - Although there are various ways in which the regulation of hypothalamic corticotropin-releasing factor (CRF) may be investigated, the most direct is by the study of CRF secretion from rat hypothalami incubated in vitro. Using this technique, we have found stimulation of secretion by noradrenaline, acetylcholine, serotonin, neuropeptide Y, and interleukins 1 and 6; inhibitory modulation was shown by GABA, substance P, atrial natriuretic peptide, opioid peptides and precursors of nitric oxide. Studies of these interactions demonstrated certain non-linear characteristics which may allow appropriate mathematical models to be devised; this may aid in our understanding of clinical disorders associated with CRF excess. PMID- 8491085 TI - Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor. AB - Most studies of the neuroendocrine effects of corticotropin-releasing factor (CRF) have focused on its role in the regulation of the pituitary-adrenal axis; activation of this axis follows release of the peptide from CRF-containing terminals in the median eminence. However, a sizeable proportion of CRF fibres terminate within the hypothalamus itself, where synaptic contacts with other hypothalamic neuropeptidergic neurons (e.g. gonadotropin-releasing hormone containing and opioidergic neurons) have been identified. Here, we summarize physiological and pharmacological data which provide insights into the nature and significance of these intrahypothalamic connections. It is now clear that CRF is a potent secretagogue of the three major endogenous opioid peptides (beta endorphin, Met-enkephalin and dynorphin) and that it stimulates opioidergic neurons tonically. In the case of beta-endorphin, another hypothalamic peptide, arginine vasopressin, appears to be an essential mediator of CRF's effect, suggesting the occurrence of CRF synapses on, or in the vicinity of, vasopressin neurons; morphological support for this assumption is still wanting. Evidence for direct and indirect inhibitory effects of CRF on sexual behaviour and secretion of reproductive hormones is also presented; the indirect pathways include opioidergic neurons. An important conclusion from all these studies is that, in addition to its better known functions in producing adaptive responses during stressful situations, CRF might also contribute to the coordinated functioning of various components of the neuroendocrine system under basal conditions. Although feedback regulation of hypothalamic neuronal activity by peripheral steroids is a well-established tenet of endocrinology, data on modulation of the intrahypothalamic actions of CRF by adrenal and sex steroids are just emerging. Some of these newer findings may be useful in framing questions related to the mechanisms underlying disease states (such as depressive illness) in which CRF has been strongly implicated. PMID- 8491086 TI - Expression of corticotropin-releasing factor mRNA in response to stress. AB - The corticotropin-releasing factor (CRF)-containing neurons of the parvocellular division of the hypothalamic paraventricular nucleus play a pivotal role in the regulation of the hypothalamo-pituitary-adrenal axis. We have studied the regulation of these neurons in the conscious rat using the technique of quantitative in situ hybridization histochemistry. Corticosteroid feedback reduces CRF mRNA levels in a dose-dependent manner, although even prolonged administration of very high doses cannot abolish CRF transcripts completely. Both physical and psychological stressors produce a robust and readily reproducible increase in CRF mRNA. These responses cannot be prevented by changes in circulating corticosteroids--a similar magnitude of response occurs with high basal levels in the adrenalectomized animal and with low basal levels during treatment with supraphysiological doses of glucocorticoid. Alterations in CRF mRNA levels in response to stress are, however, lost during the physiological condition of lactation, a state known to result in stress hyporesponsiveness, and also after 6-hydroxydopamine lesions to the catecholaminergic innervation of the paraventricular nucleus. We have also studied two conditions of chronic immunological activation of the hypothalamo-pituitary-adrenal axis--adjuvant induced arthritis and experimental allergic encephalomyelitis. Both of these results in activation of the hypothalamo-pituitary-adrenal axis with increased plasma corticosterone and ACTH, and pituitary pro-opiomelanocortin (POMC) mRNA. Unexpectedly, however, the activation of pituitary corticotrophs does not seem to be a primary result of increased activation of the CRF neurons, which actually show a consistent fall in CRF mRNA. PMID- 8491087 TI - Mechanisms mediating the effects of cytokines on neuroendocrine functions in the rat. AB - Exposure to an antigen causes significant endocrine changes, some of which in turn affect immune functioning. Proteins produced by activated immune cells, cytokines, act as messengers between the immune and the endocrine systems, and convey to the brain the occurrence of immune activation. We have investigated the ability of interleukin 1 (IL-1) alpha and beta to alter endocrine functioning in the adult rat. Acute peripheral injection of IL-1 alpha or beta causes dose dependent increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone secretion. These changes are primarily dependent upon increased release of corticotropin-releasing factor (CRF) into the portal circulation, and recent studies have indicated that the paraventricular nucleus (PVN) of the hypothalamus is the main source of this CRF. This conclusion is based on our finding that intravenous injection of IL-1 increases CRF biosynthesis in the PVN, and that lesion of this hypothalamic area interferes with IL-1's stimulatory action on ACTH secretion. Indomethacin partially reverses the effect of IL-1, suggesting that increased prostaglandin synthesis plays some part in this activation. Administration of IL-1 beta into the brain, but not into the general circulation, interferes with secretion of luteinizing hormone (LH) and ovulation through mechanisms involving endogenous opiates. Because neither CRF antagonists, nor lesions of the PVN, alter the inhibitory effect of IL-1 on LH release, CRF perikarya in the PVN do not appear to be involved in this phenomenon. Central administration of IL-1 beta strongly increases c-Fos immunoreactivity in the PVN, mainly within CRF neurons. Infusion of IL-1 beta into the PVN does not induce measurable changes in release of gonadotropin-releasing hormone (GnRH), but infusion of IL-1 directly into the median preoptic area (MPOA), a region rich in GnRH perikarya, markedly decreases GnRH secretion in rats bearing a push-pull cannula in the median eminence. Furthermore, central administration of IL-1 beta during the critical phase of pro-oestrus (1600-1930) also inhibits the expression of c-fos in GnRH cell bodies in the MPOA. Thus, we suggest that IL-1 interferes with reproductive functioning through a direct action at the level of the MPOA. These results indicate that circulating cytokines can alter the activity of the hypothalamo-pituitary-adrenal axis by increasing CRF release, probably through both immediate stimulation of CRF terminals within the median eminence and stimulation of CRF synthesis in the PVN. In contrast, cytokine-induced changes in LH and GnRH secretion are mediated through pathways lying primarily beyond the blood-brain barrier. PMID- 8491088 TI - Infection as a stressor: a cytokine-mediated activation of the hypothalamo pituitary-adrenal axis? AB - Infections are associated with increased plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone. Hypothalamo-pituitary adrenal (HPA) responses have also been observed with immunological stimuli that are not infective. Although such responses have been suggested to be mediated by ACTH secreted by lymphocytes, adrenocortical activation by immunological stimuli requires a functional pituitary. The most likely mechanism by which immunological stimuli activate the HPA axis involves production of cytokines by lymphocytes. The prime candidate is interleukin 1 (IL-1), because IL-1 production follows activation of the immune system and IL-1 administration is a potent activator of the HPA axis. However, other cytokines, such as tumour necrosis factor, may also be involved. Most immunological stimuli and IL-1 also activate both peripheral and central noradrenergic neurons. IL-1-induced activation of the HPA axis in vivo depends upon secretion of corticotropin-releasing factor (CRF), an intact pituitary, and the ventral noradrenergic bundle which innervates the CRF containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Besides elevating body temperature, administration of IL-1 elicits a number of behavioural responses in rats and mice, including anorexia, increased sleep time, decreased investigation of novel objects and other animals, increased defensive withdrawal and other behaviours characteristic of sickness. Some of these responses can be reversed by CRF-antagonists and mimicked by CRF administration. Thus, endogenous production of IL-1 can account for a range of physiological and behavioural responses characteristic of sickness. Nevertheless, definitive evidence that IL-1 mediates these responses in sick animals is lacking. PMID- 8491089 TI - Central actions of corticotropin-releasing factor on autonomic nervous activity and cardiovascular functioning. AB - The physiological role of corticotropin-releasing factor (CRF) in mediating stress-induced activation of the pituitary-adrenal axis, together with the neuroanatomical distribution of immunoreactive CRF and CRF receptors, provides a compelling rationale for investigating actions of CRF within the central nervous system (CNS) on autonomic nervous outflow and cardiovascular function. Evidence is reviewed showing that CRF acts within the CNS to elicit stress-like patterns of autonomic nervous outflow and cardiovascular changes in conscious animals. In addition, blockade of CRF-mediated neurotransmission is demonstrated to alter the expression of stress-induced autonomic nervous and cardiovascular responses. Together, the anatomical, pharmacological and physiological data support the hypothesis that the autonomic nervous and cardiovascular responses to selected stressful stimuli may be mediated in part by CRF-containing neuronal pathways. PMID- 8491090 TI - The role of corticotropin-releasing factor in behavioural responses to stress. AB - Corticotropin-releasing factor (CRF), when administered directly into the CNS, can have activating properties on behaviour and can enhance behavioural responses to stress. CRF injected intraventricularly produces a dose-dependent increase in locomotor activity and increased responsiveness to an acoustic startle stimulus. However, this profile of activation changes to enhanced suppression of behaviour in stressful situations and includes increased freezing, increased conditioned suppression, increased conflict, decreased feeding and decreased behaviour in a novel open field. These effects of CRF are independent of the pituitary-adrenal axis and can be reversed by the CRF antagonist alpha-helical CRF(9-41). More importantly, the CRF antagonist can also reverse many behavioural responses to stressors. alpha-Helical CRF(9-41) reverses stress-induced fighting behaviour, stress-induced freezing, stress-induced suppression of feeding, stress-induced decreases in exploration of an elevated plus maze, fear-potentiated startle and the development of conditioned suppression. Intracerebral microinjections suggest that the amygdala may be an important site for the anti-stress effects of alpha helical CRF(9-41). These results suggest that endogenous CRF systems in the CNS may have a role in mediating behavioural responses to stress and further suggest that CRF in the brain may function as a fundamental behavioural activating system. This CRF system may be particularly important in situations where an organism must mobilize not only the pituitary-adrenal system but also the CNS in response to environmental challenge. PMID- 8491091 TI - The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. AB - The unique distribution of corticotropin-releasing factor (CRF) and its receptors within the central nervous system, its pre-eminent role in mediating the endocrine, behavioural, autonomic and immunological effects of stress and its potent effects after direct administration into the CNS all support the hypothesis that alterations in CRF neuronal systems contribute to the pathophysiology of depression and certain anxiety disorders. This report summarizes a series of preclinical and clinical investigations which have sought to test the hypothesis that CRF-containing neurons show alterations in depression and anxiety, and that drugs used to treat these disorders alter CRF neuronal circuits. Direct injection of CRF into the locus ceruleus or nearby parabrachial nucleus evokes an anxiogenic response. Stress increases CRF concentrations in the locus ceruleus, whereas alprazolam, a benzodiazepine anxiolytic, decreases the concentration of the peptide in the same area. Clinical studies reveal that drug free depressed patients show: (1) hyperactivity of the hypothalamo-pituitary adrenal axis; (2) increased CRF concentrations in the cerebrospinal fluid; (3) a blunted release of ACTH in response to CRF; (4) a reduced density of CRF receptors in the frontal cortex; (5) pituitary and adrenal gland hypertrophy. These findings are all concordant with hypersecretion of CRF from hypothalamic and extrahypothalamic CRF neurons in depression. PMID- 8491092 TI - Second messenger regulation of mRNA for corticotropin-releasing factor. AB - An understanding of how second messengers and their ligands are coupled to CRF gene activation is necessary if we are to understand the regulation of the CRF gene in physiological and pathological states. The protein kinase A, protein kinase C and glucocorticoid second messenger systems mediate most of the regulation of the CRF gene. In in vitro systems, CRF gene expression is stimulated 20-30-fold by activation of either the protein kinase A or the protein kinase C system. Glucocorticoid is able to inhibit stimulation via both pathways, but appears to be more effective in repressing activation mediated by protein kinase C. Glucocorticoid negative regulation requires the presence of glucocorticoid receptor possessing an intact DNA-binding domain, suggesting that this effect involves binding of the receptor to the CRF promoter. These in vitro studies should serve to guide investigators towards the possible mechanisms underlying CRF gene regulation in vivo. PMID- 8491093 TI - The role of corticotropin-releasing factor in the investigation of endocrine diseases. AB - Since the discovery and structural elucidation of corticotropin-releasing factor (CRF) synthetic ovine and human CRF have become useful tools for the diagnosis of pituitary and adrenocortical disorders. The stimulation of release of adrenocorticotropic hormone (ACTH) after a dose of 100 micrograms CRF allows differentiation of the various causes of secondary adrenal insufficiency. In patients with specific autoimmune corticotroph disorders or general inflammatory or tumorous destruction of the anterior pituitary there is no rise of ACTH after intravenous administration of CRF. In contrast, patients with secondary adrenal failure due to suprasellar lesions show a rise of ACTH from a low or unmeasurable basal level without an accompanying cortisol response, demonstrating the integrity of the corticotroph and the atrophy of the cRF neuron and the adrenocortical cell. Similar observations are made in patients with secondary adrenal failure resulting from long-term glucocorticoid treatment. This demonstrates that the main reason for adrenal insufficiency after glucocorticoid treatment is the persisting suppression of the activity of CRF neurons. In patients with adrenocortical hyperfunction (Cushing's syndrome) the CRF stimulation test differentiates unequivocally between autonomous adrenal hypercortisolism and ACTH-dependent bilateral adrenal hyperplasia. However, the differential diagnosis between eutopic pituitary (Cushing's disease) and paraneoplastic ACTH secretion (ectopic ACTH syndrome) is difficult. Recent results show that catheterization of the sinus petrous inferior and measurement of ACTH in central and peripheral blood before and after CRF injection allows this differential diagnosis to be made with confidence. The usefulness of measuring CRF plasma levels is not established. The only exception to this is in cases of ectopic CRF syndrome, which is a rare cause of Cushing's syndrome. PMID- 8491094 TI - The functional neuroanatomy of corticotropin-releasing factor. AB - Descriptions of the central distribution of corticotropin-releasing factor (CRF) have been taken as generally supporting the proposition that this neuropeptide is involved in the mediation of complementary neuroendocrine, autonomic and behavioural responses to stress. The hypothalamic paraventricular nucleus (PVN) is recognized as the principal source of CRF in hypophysial portal plasma; CRF mRNA and peptide expression in parvocellular neurosecretory neurons are regulated negatively by adrenal steroids and positively by many stressors. Consistent with the latter, the hypophysiotropic zone of the PVN receives a rich, and biochemically differentiated, afferent supply that provides visceral, somatic and special sensory systems with access to the 'CRF neuron'. Within the PVN, CRF is also expressed, and differentially regulated, in oxytocinergic magnocellular neurosecretory neurons and in autonomic-related projection neurons. CRF expression in at least some extrahypothalamic cell groups (olfactory bulb, Barrington's nucleus) is responsive to certain stressful stimuli, but not to perturbations of the steroid environment. Refinement of our understanding of the central distribution of CRF has been provided by the recognition that most CRF antisera cross-react with an amidated dipeptide encoded by the melanin concentrating hormone precursor, and by the likelihood that some central sites of CRF peptide expression may be muted or masked by the presence of a CRF-binding protein (CRF-BP). The CRF-BP is expressed prominently in the telencephalon, where it is co-localized with CRF in some neurons, and in anterior pituitary corticotrophs. PMID- 8491095 TI - Central and feedback regulation of hypothalamic corticotropin-releasing factor secretion. AB - Physical, emotional and metabolic stressors activate the hypothalamo-pituitary adrenal (HPA) axis via multiple neural pathways. Final hypothalamic coding of stressor-induced adrenocorticotropic hormone (ACTH) secretion is mediated by differential release of ACTH secretagogues. These include, but may not be limited to, corticotropin-releasing factor (CRF), arginine vasopressin, oxytocin and, possibly, adrenaline. Among these substances, CRF serves as the predominant regulatory factor of this axis because its presence is obligatory for the action of intrinsically weaker secretagogues. Because neural input-encoding qualities of individual stressors utilize, in part, stimulus-specific pathways, the effectiveness of glucocorticoid negative feedback in modulating ongoing and subsequent activity of the HPA axis is dependent upon the type of stressor and the nature of the neural pathways mediating the initial activity. Studies suggest that responses to physical stressors (for example, haemorrhage) are resistant to classical intermediate feedback, whereas those to emotional/cognitive stressors (such as a novel environment) are strongly susceptible to feedback. Overall functional characteristics of the HPA axis in adult organisms are at least partially a result of neonatal experience. In the adult differences in hypothalamic CRF mRNA levels, median eminence peptide content and pituitary responsiveness to stressors can be correlated with aspects of neonatal experience. PMID- 8491096 TI - Muscle histopathology and physiology in chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) is characterized by fatigue at rest which is made worse by exercise. Previous biopsy studies on small numbers of CFS patients have shown a range of morphological changes to which have been attributed fatigue and myalgia. We have now studied 108 patients with CFS or muscle pain and 22 normal volunteers by light and electron microscopy. There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities. Physiological contractile properties of quadriceps (maximal isometric force generation, frequency: force characteristics and relaxation rate) were also examined before and for up to 48 hours after a symptom-limited incremental cycle ergometer exercise test in 12 CFS patients and 12 normal volunteers. Voluntary and stimulated force characteristics were normal at rest and during recovery. Exercise duration was similar in the two groups although CFS patients had higher perceived exertion scores in relation to heart rate during exercise, indicating a reduced effort sensation threshold. On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition. PMID- 8491097 TI - Immunity and the pathophysiology of chronic fatigue syndrome. AB - The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found. Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used. The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis. PMID- 8491098 TI - The relationship of chronic fatigue to psychiatric illness in community, primary care and tertiary care samples. AB - This paper reviews the psychiatric disorders associated with the symptom of fatigue in community, primary care and tertiary care samples. In each of these subsamples, studies using structured psychiatric interviews and operational diagnostic criteria are compared and contrasted. In summary, in community, primary care and tertiary care populations, there was a high association between the symptom of fatigue and affective and anxiety disorders. The prevalence rates of affective illness went up linearly in patients with fatigue as one moved from community to primary care and tertiary populations. The fact that fatigue is a common symptom in the community and is associated with significantly higher medical utilization when associated with affective and anxiety disorders may explain the increased association between this symptom and affective illness in primary and tertiary care. PMID- 8491099 TI - The neuropsychiatry of chronic fatigue syndrome. AB - This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be 'brainless' and neurology to be 'mindless' have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS. PMID- 8491100 TI - Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification. AB - To determine the medical and psychiatric diagnoses that have an aetiological role in chronic fatigue we conducted a prospective study of 405 (65% women) patients who presented for evaluation with this chief complaint to an academic medical centre. The average age was 38.1 years and the average duration of fatigue at entry in the study was 6.9 years. All patients were given comprehensive physical and laboratory evaluations and were administered a highly structured psychiatric interview. Psychiatric diagnoses explaining the chronic fatigue were identified in 74% of patients and physical disorders were diagnosed in 7% of patients. The most common psychiatric conditions in this series were major depression, diagnosed in 58% of patients, panic disorder, diagnosed in 14% of patients, and somatization disorder, diagnosed in 10% of patients. Primary sleep disorders, diagnosed in 2% patients, and chronic infections, confirmed in 1.6% patients, explained the majority of cases whose chronic fatigue was attributed to a physical disorder. Thirty per cent of patients met the criteria used to define the chronic fatigue syndrome (CFS). Compared with age- and gender-matched control subjects with chronic fatigue, CFS patients had a similarly high prevalence of current psychiatric disorders (78% versus 82%), but were significantly more likely to have somatization disorder (28% versus 5%) and to attribute their illness to a viral infection (70% versus 33%). We conclude that most patients with a chief complaint of chronic fatigue, including those exhibiting the features of CFS, suffer from standard mood, anxiety and/or somatoform disorders. Careful research is still needed to determine whether CFS is a distinct entity or a variant of these psychiatric illness. PMID- 8491101 TI - Somatization, illness attribution and the sociocultural psychiatry of chronic fatigue syndrome. AB - In addition to epidemiological and neurobiological perspectives on the relationship between chronic fatigue syndrome (CFS) and psychiatric disorders there has been increasing interest in the role of cognitive-behavioural, psychological, psychodynamic and social factors in the psychiatric aspects of this syndrome. These factors may be important in the initiation and/or maintenance of CFS and play important roles in the misdiagnosis of primary psychopathology as CFS. They may be important targets for intervention and treatment. This paper examines the relevance of the following issues for better understanding the relationship between CFS and the results of psychiatric studies: (1) the concepts of somatization and abnormal illness behaviour; (2) the role of patients' illness attributions; (3) psychological and psychodynamic constructs such as depressive vulnerability occurring in individuals dependent upon achievement for the maintenance of self-esteem and euthymic mood, perfectionism, and helplessness; (4) the role of personality characteristics and styles; (5) the potential iatrogenic role of the health care system in producing disability in individuals with a diagnosis of CFS; (6) the role of the media and other sociocultural forces in the patient's choice of the CFS label; and (7) the impact of the CFS label on the patient. The importance of differentiating between initiating and maintaining or perpetuating factors is emphasized. PMID- 8491102 TI - Fibromyalgia, sleep disorder and chronic fatigue syndrome. AB - Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder. In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness. The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system. The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome. PMID- 8491103 TI - Pharmacological approaches to the therapy of chronic fatigue syndrome. AB - Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms. Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression. Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials. PMID- 8491104 TI - Non-pharmacological approaches to treatment. AB - Chronic fatigue syndrome (CFS) as currently defined overlaps with other syndromes including chronic pain, fibromyalgia, anxiety and depression. It also resembles historical descriptions of neurasthenia. The role of psychological (cognitive) and behavioural therapies in CFS is examined. There are both pragmatic and theoretical arguments for their application to CFS. It is pragmatic to target obvious and treatable factors including inactivity and depression. A theoretical model in which psychological, physiological and social factors interact offers a plausible rationale for such treatment but is not yet empirically proven. While there is evidence for the efficacy of this type of therapy in related syndromes, the evidence in CFS is inconclusive. A randomized controlled trial of combined cognitive and behavioural therapy currently in progress is described. Initial results suggest that most patients receiving cognitive behaviour therapy improve, especially in terms of functional impairment. It remains to be seen whether this therapy will prove to be more effective than standard general practitioner care. In the meantime cognitive behaviour therapy offers a pragmatic and rational therapy for patients with CFS. PMID- 8491105 TI - Chronic fatigue syndrome and the treatment process. AB - Fatigue is a common complaint in general practice and is often associated with psychiatric and psychosocial problems and demoralization. Although the Centers for Disease Control definition of chronic fatigue syndrome (CFS) excludes pre existing psychiatric illness, common psychosocial problems short of a clinical disorder (such as irritability, difficulty in thinking, inability to concentrate, depression and sleep disturbance) overlap with the criteria for CFS. Psychological states can affect the course of CFS or become confused in the patient's and doctor's mind with the course of infection. The core dilemma in practice is how aggressively to pursue a possible basis for CFS when it persists in the absence of an identifiable external cause. Possibilities for exploration are numerous and potentially expensive. In practice, the persistence of doctors depends on the patient's illness behaviour, on financial and organizational factors, and on the culture of medical care and practice styles. It is essential to differentiate the appropriate management of CFS from scientific study where intensive investigation may be warranted. In practice doctors should proceed in a manner that conveys concern, supports function, and avoids dysfunctional illness behaviour and inadvertent legitimization and reinforcement of disability. PMID- 8491106 TI - Clinical presentation of chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) is a chronic illness of uncertain aetiology characterized by at least six months of debilitating fatigue and associated symptoms. The symptoms of the syndrome are all non-specific and some (but not all) are also seen in psychiatric illness. The symptomatology suggesting an organic component to the illness includes its abrupt onset with an 'infectious like' illness, intermittent unexplained fevers, arthralgias and 'gelling' (stiffness), sore throats, cough, photophobia, night sweats, and post-exertional malaise with systemic symptoms. The illness can last for years and is associated with marked impairment of functional health status. PMID- 8491107 TI - Chronic fatigue in historical perspective. AB - Chronic fatigue as a presenting complaint, in the absence of other evident organic illness, was seldom reported historically before the second half of the 19th century. Its first eruption was the so-called 'bed cases' or 'sofa cases' among middle-class females in the period from 1860 to about 1910. 'Neurasthenia' does not necessarily represent an early forerunner of chronic fatigue. Many patients receiving that diagnosis did not complain of fatigue. Others with functional fatigue did not receive the diagnosis 'neurasthenia'. Both medical anecdotal and quantitative sources make it clear that by the time of the First World War, chronic fatigue was a common complaint in Europe and North America. Medical concepts of chronic fatigue since the 1930s have run along four separate lines: (1) 'postinfectious neuromyasthenia', going back to an atypical 'poliomyelitis' epidemic in 1934; (2) 'chronic Epstein-Barr virus' infection, an illness attribution that increased in frequency after the discovery in 1968 that this virus caused mononucleosis; (3) 'myalgic encephalomyelitis', dating from an epidemic at the Royal Free Hospital in London in 1955; and (4) 'fibrositis', or 'fibromyalgia', used as a rheumatological description since the turn of the century. Recently, these four separate paths have tended to converge into the diagnosis of 'chronic fatigue syndrome'. PMID- 8491108 TI - Society, mind and body in chronic fatigue syndrome: an anthropological view. AB - An anthropological view of chronic fatigue syndrome places the study of illness in social context. Data from an interview study of 50 chronically fatigued patients demonstrate the relation of local social worlds--families, workplaces, communities--to the meaning and experience of illness. Negative life events and difficulties, multiple commitments, and a hectic pace are among prominent themes in the subjects' local worlds. These themes are reflected in: (1) attributions of illness onset to social sources, (2) the symbolism of the core complaint of fatigue, and (3) an illness-induced, positively valued lifestyle transformation suggesting the rejection of culturally prescribed 'busyness'. Dichotomous definitions of the relation of mind and body are shown to be part of culture, not Nature, in the paper's second section. The 'mind-body dichotomy' and the differing values attached to physical and psychological disorders by a naturalistic scientific paradigm explain the delegitimizing experiences of sufferers, who find their illness dismissed as psychosomatic and therefore 'not real'. A conceptualization of chronic fatigue syndrome which links local social worlds to psychological distress, felt bodily sensation and biological changes is proposed. Collaborative teams of social scientists and medical researchers might fruitfully pursue aspects of social context in relation to psychiatric, immunological and viral dimensions of the illness. PMID- 8491109 TI - Visual diagnosis of hematologic and oncologic diseases. AB - Cancer-related problems are seen frequently by the emergency physician. More difficult presentations are seen with premonitory symptoms, paraneoplastic syndromes, and nonspecific lesions. Dermatologic paraneoplastic syndromes are numerous, nonspecific, and consist of hamartomatous growths, texture changes, new hair growth, or changes in skin color. Alteration of skin color may be of practically any color, localized or diffuse, and of sudden or indolent onset. Hormone production by tumors may lead to acne, hirsutism, gynecomastia, or a cushingoid appearance. Pruritus may herald the onset of leukemia or lymphoma and be intolerable, as with erythroderma. All suspicious presentations require thorough investigation for underlying disease. Metastasis to skin is not common and implies a poor prognosis if seen. Most metastases are seen on the head and neck, anterior chest wall, and abdomen. Basal cell and squamous cell carcinomas commonly occur in sun-exposed areas. Basal cell is locally destructive, whereas squamous cell occasionally metastasizes to local lymph nodes. Malignant melanoma is the leading fatal illness originating in skin, with a dramatic rise in incidence. It is classically described as asymmetric with irregular borders, is elevated, and shows color variegation; however, melanoma may present atypically, particularly in non-whites. Kaposi's sarcoma lesions are well-demarcated, symmetric, smooth nodules that appear purplish-brown, particularly if below the knee (owing to venous stasis). The closely interrelated structures of the eye and orbit are easily disturbed, leading to the presenting symptoms of visual disturbances, exophthalmos, pain, and ocular motility disorders. Primary tumors are not unusual and may include retinoblastoma, rhabdomyosarcoma, and melanoma. Equally common are metastatic lesions, most commonly lung and breast carcinoma. An estimation of the malignancy of bony lesions can be made by assessing the zone of transition, periosteal reaction, and bone destruction. A malignant lesion will more likely have a broad zone of transition, irregular periosteal reaction, and moth-eaten or permeative destruction of trabeculae. Metastatic bone lesions primarily occur in sites of persistent red marrow: skull, ribs, vertebrae, pelvis, and proximal humerus and femur. Bony lesions can be blastic or lytic in nature. Solitary pulmonary nodules that have not grown for 2 years can be assumed to be benign. Calcification seen on plain films are a strong (but not absolute) indication of benignancy. Lesions that are greater than 3 to 4 cm in diameter, have irregular contours, are cavitated with thick walls, have multiple peripheral nodules, and have lack of calcification are more likely malignant. PMID- 8491110 TI - Hemophilia. AB - Hemophilia and von Willebrand's disease are the most common hereditary bleeding disorders. A variety of treatment modalities of these disorders are discussed. Common organ system bleeding and its treatment and disposition are outlined. Finally, potential complications of both the disease and treatment are reviewed. PMID- 8491111 TI - Emergencies in sickle cell disease. AB - Sickle cell disease in its heterozygous and homozygous forms exhibits diverse, debilitating pathologic manifestations. No organ system is spared from the effects of chronic hypoxia and poor rheology. The emergency physician should be familiar with the typical complications of SCA, because in large part these problems can either be managed in the ED or require emergent, focused evaluation and referral. PMID- 8491112 TI - Transfusion therapy in the emergency department. AB - This article reviews the basics of blood and blood component therapy, focusing on pretransfusion compatibility testing and the complications of blood transfusion (both infectious and noninfectious). Issues surrounding the massive transfusion of blood and alternatives to traditional chemotherapy also are discussed. PMID- 8491113 TI - Medical complications of oncologic disease. AB - Oncologic patients in urgent medical crises frequently are seen in the Emergency Department. Hypercalcemia, tumor lysis syndrome, hyperviscosity syndrome, and the syndrome of inappropriate antidiuretic hormone are four metabolic complications that have life-threatening implications. This article reviews these conditions from the perspective of the emergency physician. Clinical presentation, pathophysiology, and management specific to each entity are discussed. PMID- 8491114 TI - Mechanical complications of cancer. AB - Emergency physicians can expect to see more patients with malignancies. Some of these malignancies can lead to life-threatening emergencies, and the emergency physician must suspect and be able to recognize these problems. PMID- 8491115 TI - Pharmacology and toxicology of chemotherapeutic agents. AB - Emergency physicians often must evaluate symptomatic cancer patients receiving chemotherapeutic agents. When assessing patients being administered such highly toxic agents that have a narrow therapeutic index, fundamental understanding of the pharmacology and recognition of the toxic manifestations is mandatory. This article reviews some of the more commonly used chemotherapeutic agents, with particular emphasis on their indications, mechanisms of action, and toxicity. PMID- 8491116 TI - Thrombocytopenia. AB - Emergency physicians often must evaluate patients with thrombocytopenia. Once recognized, the initial concern is for evaluating the patient's hemostasis. Prompt diagnosis and early intervention may be life saving. This article reviews platelet function and kinetics and presents the pathophysiology and clinical and laboratory findings of a number of diagnoses that are included in the differential diagnosis of thrombocytopenia. The general as well as specific approach to the patient is outlined. PMID- 8491117 TI - Disseminated intravascular coagulation. AB - DIC is a consumptive thrombohemorrhagic life-threatening disorder resulting in multiple coagulation, platelet, and fibrinolytic abnormalities. The causes are legion. Diagnosis is both clinical and laboratory based. Therapy remains controversial and should be based on clinical presentation, although some clinical syndromes may allow for specific treatment. Despite aggressive therapy and research, mortality remains high. Recognition of the patient at risk as well as treatment of the underlying disorder is the critical role for the emergency physician. PMID- 8491118 TI - Selected red cell disorders. AB - Effective red blood cell function is vital to maintaining homeostasis. A host of quantitative and qualitative RBC defects compromise this function to varying degrees and can therefore threaten survival. Knowledge of these disease states and expertise in the diagnosis and management of them is essential to avoid physiologic decompensation and restore well-being. PMID- 8491119 TI - Selected white cell disorders. AB - The emergency physician frequently is confronted with an abnormal white blood cell count when evaluating patients. Leukocytosis may be caused by malignancy, infection, or a variety of other reasons. Leukopenia is an increasingly common finding as the population of immunocompromised patients continues to expand. This article reviews the differential diagnosis of leukocytosis and leukopenia. The management of the neutropenic patient with and without fever is also reviewed and includes currently recommended empiric antibiotic regimens. PMID- 8491120 TI - Emergency department presentation of childhood malignancies. AB - The diagnosis of malignancy in childhood is challenging. Signs and symptoms are generally nonspecific, and children with an underlying malignancy rarely are seriously ill at the time of initial presentation. A thorough history and physical examination are the most important components of the emergency physician's assessment of children in whom cancer is suspected. There are a number of risk factors, physical findings, and clinical syndromes that indicate the need for careful evaluation of which the emergency physician should be aware. PMID- 8491121 TI - Ethical dilemmas in hematologic/oncologic emergencies. AB - Clinicians use ethical decision making in their practice by applying professional and societal values in an organized way to solve moral dilemmas. Moral dilemmas are those situations in which a decision must be made between conflicting goods or evils or rights or wrongs. Clinicians must understand the medical profession's and society's values and be able to apply them within ethical systems. This article describes those values, basic ethical systems, a rapid ethical decision making model, and specific ethical dilemmas faced by emergency physicians who treat patients with hematologic and oncologic emergencies. PMID- 8491122 TI - Biocompatibility of dentin bonding agents. AB - Dentin bonding agents were introduced to enhance the bonding of composite resins to dentin. Many commercial brands of bonding agents are now available for clinical use, and they are getting more and more popular. The third generation of dentin bonding agents seems to be more effective than earlier generations, although more complex to use. Dentin bonding agents have different chemical compositions, different mechanism of action, and different clinical application procedures and, conceivably, different biological effects on the pulpal tissues are expected. The reported biological effects of dentin bonding agents ranged from none to severe, depending on several factors. Opinions varied whether the inflammatory reactions associated with some bonding agents were due to the material per se, to bacterial ingrowth at the tooth restoration interface, or due to a combination of both factors. PMID- 8491123 TI - Endodontic status of mandibular premolars and molars in an adult Swedish population. A longitudinal study 1974-1985. AB - The purpose of the investigation was to study the incidence of endodontic treatment and the progression of periapical disease in an adult Swedish population. A random sample was selected in 1974 and offered a clinical and radiographic examination. In 1985, 345 of the original 1302 persons received a follow-up examination. The present study was based on information obtained from radiographs of the mandibular premolar and molar regions at the two examinations. The highest increase in people with endodontically treated teeth from 1974 to 1985 and the highest increase in people with periapical lesions were found in the youngest age-group, born between 1945 and 1954. New endodontic treatment, received between 1974 and 1985, was mostly found among those who already had endodontically treated teeth in 1974. New periapical lesions also appeared more often in persons with endodontic disorders in 1974. PMID- 8491124 TI - Introduction to four custom-made mouth protectors constructed of single and double layers for activists in contact sports. AB - Four mouth protectors are introduced, all manufactured by dentists familiar with small-scale technical work. Mouth protectors made of Erkoflex or Erkoloc sheets are moulded in an Erkopress device under a vacuum, while the TranSheet/Perform and TranSheet/LiteLine mouth protectors are constructed of a hard outer shell (Triad TranSheet, light-cured polyurethane dimethacrylate) and a soft inner part against the labial surface of the front teeth (Perform or LiteLine, both light cured polyurethane dimethacrylate), thus minimizing the impact on individual teeth and better preventing dental traumas. The technical construction of the mouth protectors is illustrated, as is the need for instrumentation and its costs and the materials required to manufacture these mouth protectors. PMID- 8491125 TI - Effect of intracanal dressings on repair and apical bridging of teeth with incomplete root formation. AB - Periapical repair and apical bridging were studied in dog's teeth with incomplete root formation and induced chronic periapical lesions treated with different dressings. A total of 75 root canals from the upper and lower premolars of 4 dogs approximately 6 months of age were chemo-mechanically prepared and filled with the following dressings: antibacterial dressing consisting of a calcium hydroxide+camphorated p-monochlorophenol paste applied for 7 days and followed by monthly renewed calcium hydroxide paste as temporary dressing at 30, 60 and 90 days (Group A); antibacterial dressing consisting of camphorated p monochlorophenol alone for 7 days, followed by temporary dressing with calcium hydroxide paste renewed at 30, 60 and 90 days (Group B). A control group (Group C) received no dressings. Ninety days after the last calcium hydroxide paste (Groups A, B) and after the last irrigation/aspiration (Group C), the animals were killed, the maxillae and mandibles were removed, and the material submitted to routine histological processing and examination. Both root canal dressings, were of fundamental importance for apical repair and bridging. The apical bridging was predominantly complete in Group A, incomplete in Group B, and absent in Group C. The calcium hydroxide+camphorated p-monochlorophenol combination gave better results than camphorated p-monochlorophenol alone. PMID- 8491126 TI - Action of adrenaline on the effect of dental local anaesthetic solutions. AB - This study investigated the effects of dental local anaesthetic solutions containing either 2% plain lignocaine or 2% lignocaine with 1:80,000 adrenaline. The duration of anaesthesia and the occurrence of a reduction in blood flow together with its duration were examined in the dental pulps of maxillary central incisor teeth in 10 human subjects. The local anaesthetic solution was injected into the soft tissues adjacent to the apex of the sound maxillary incisor tooth. The blood flow in the dental pulp was assessed by a laser Doppler flowmeter, and the effectiveness of pulpal anaesthesia was determined by an electric pulp tester, both at timed intervals. The injection of 1-2 ml of 2% plain lignocaine had no significant effect on blood flow in the pulp of the incisor tooth in eight of 10 subjects. In the other two, there was a small but significant increase. The duration of pulpal anaesthesia was 25.1 min (SD 6.23). Following injection of 1 ml of 2% lignocaine with 1:80,000 adrenaline, there was a significant reduction (31%) of pulpal blood flow in every subject (p < 0.05). The duration of reduced blood flow was 68.5 min (SD 9.73). The duration of pulpal anaesthesia was 100 min (SD 15.09), four times the duration of anaesthesia induced by plain lignocaine. The anaesthetic solution with vasoconstrictor produced far longer anaesthesia more consistently at a lower dose than the plain solution. PMID- 8491127 TI - Autotransplantations and loss of anterior teeth by trauma. AB - The loss of anterior teeth by trauma has usually been corrected by orthodontic or prosthetic means. In some specific cases, however, the skeletal and dental relationship may contraindicate the use of space-closure mechanics. Autotransplantation of teeth, successfully depicted in many clinical studies, can help to reduce the severity of orthodontic cases complicated by traumatized anterior teeth. A case report is presented to stress both the indications and limitations of such treatment. PMID- 8491128 TI - Repair of untreated root fracture: a case report. AB - A case is presented in which an untreated root fracture in a maxillary central incisor of an adult male was found radiographically 10 years after injury. The tooth was removed and the area of the root corresponding to the fracture line was examined by SEM while the remaining tooth was processed for decalcified sections. Calcification of the coronal pulp associated with extensive tissue atrophy and normal pulp tissue apically was observed. Two barriers composed of dentinal and cemental hard tissue were present apically in the coronal fragment and in the fracture line. PMID- 8491129 TI - Healing process of dogs' pulpless teeth after apicoectomy and root canal filling at different levels. AB - Dogs' teeth with infected root canals, were submitted to apicoectomy and the root canals were filled flush or 2 mm short. In a third group the canals were left unfilled and only the access openings were closed. One hundred and eighty days after the treatment, the animals were killed and the specimens prepared for histological analysis. Repair was not observed in the teeth with unfilled root canals. The healing observed in the teeth with root canals filled flush was less complete than the healing observed when the root canals were filled 2 mm short. PMID- 8491130 TI - Endoscopic ultrasonography in the diagnosis and staging of pancreatic adenocarcinoma. Results of a prospective study with comparison to ultrasonography and CT scan. AB - Endoscopic ultrasonography (EUS) was compared to ultrasonography (US) and CT scan (CT) in order to evaluate its role in the diagnosis and the locoregional spread assessment of pancreatic cancer. Sixty-four patients suspected of pancreatic cancer were studied prospectively, and the results of imaging techniques were compared to histology and surgical exploration. There were 49 cases of pancreatic adenocarcinoma, 11 of pancreatitis, 2 of common bile duct carcinoma, 1 lymphoma and 1 hepatocellular carcinoma with peripancreatic metastatic lymph nodes. EUS was significantly more accurate (91%) than CT (66%) and US (64%) for diagnosis of pancreatic cancer. EUS was able to image all 7 cancers less than 25 mm in diameter, US and CT only one. There were 4 false positives with EUS which were all cases of pseudotumorous pancreatitis. For detecting lymph node involvement, EUS was significantly more sensitive (62%) and accurate (74%) than US (8% and 37%) and CT (19% and 42%), respectively. Invaded lymph nodes adjacent to large tumors and micrometastatic involvement were responsible for this lack of sensitivity. EUS was significantly more sensitive (100%) than CT (71%) and US (17%) for detecting venous involvement. The specificity of EUS was lower (67%) because of duodenal bulb stenosis and large tumors. In conclusion, this prospective and comparative study confirms that EUS is an accurate tool for diagnosis and locoregional spread assessment of pancreatic cancer when performed in a reference center. EUS is of particular interest for small tumours. However, EUS does not enable differentiation of pseudotumorous pancreatitis from adenocarcinoma. PMID- 8491131 TI - Staging of pancreatic carcinoma by endoscopic ultrasonography. AB - The ability of EUS to diagnose small pancreatic cancer is well known. In this study, we present our experience with EUS in the local staging of 29 patients with pancreatic carcinoma who underwent surgery. EUS was 79, 83 and 79% accurate in determining anterior (including gastric), duodenal and retroperitoneal (vascular) invasion by the tumor. Ultrasonography (48, 39 and 55%, respectively) and CT (38, 33 and 41%, respectively) were less reliable. EUS was equal to angiography in diagnosing vascular involvement. EUS was more effective in detecting splenoportal infiltration (sensitivity 88%, specificity 78%) than arterial involvement (accuracy 50%). EUS was also less reliable in determining the N stage (66%) and in stage grouping (72%). Although EUS is superior to ultrasonography and CT in the local staging of pancreatic carcinoma, further studies must show whether improved staging criteria will lead to better results. PMID- 8491132 TI - Role of endoscopic ultrasonography in esophageal carcinoma. AB - One hundred and sixty seven consecutive patients with esophageal carcinoma (squamous cell carcinoma: n = 108, adenocarcinoma: n = 59) who underwent surgery were preoperatively examined by endoscopic ultrasonography (EUS), and the results were compared with intraoperative exploration and histopathological evaluation of resection specimens. The T and N stage were correctly determined by EUS in 86% and 73%, respectively. The assessment of the T stage for cases with traversable (n = 124) versus non-traversable (n = 43) tumor stenoses was 85% and 70%, respectively. Prediction of resectability by EUS (89%) was correct for adenocarcinoma (82% actual R0 resection rate), but not for squamous cell cancer (64%). This was due to the high incidence of submucosal microscopic tumor spread of squamous cell cancer not detectable on EUS. We consider EUS an indispensable diagnostic tool in the local staging of esophageal cancer since it provides important information in the assessment of resectability, aids in therapeutic decisions and in determining the prognosis. Our comparably low rate of primary surgery (66%) and the high resection rate of 95% are due to the exact preoperative staging by EUS. PMID- 8491133 TI - Role of endoscopic ultrasonography in gastric carcinoma. AB - Two hundred and fifty four consecutive patients with gastric adenocarcinoma who underwent surgery were preoperatively evaluated with endoscopic ultrasonography (EUS). The results were compared with the post-operative histo-pathological staging. EUS was correct in determining the T and N stage in 83% and 66%, respectively. Although EUS was accurate in determining the absence of lymph node metastases (accuracy in stage N0: 93%), it was not reliable in determining stages N1 and N2 (64% and 52%, respectively). Since 88% of all T3 and T4 tumors had lymph node metastases, the concomitant T stage may be an important criterion for assessing the nature of endosonographically visualized lymph nodes. The actual R0 resection rate (78%) was almost identical to the rate predicted preoperatively by EUS (81%). We therefore consider EUS a valuable pretherapeutic procedure in patients with gastric carcinoma. PMID- 8491134 TI - Endoscopic hemoclip treatment for gastrointestinal bleeding. AB - We conducted an uncontrolled study to evaluate an improved metallic clip (Olympus hemoclip) for the endoscopic treatment of nonvariceal gastrointestinal bleeding. A total of 88 patients (mean age 63 +/- 14, 60 males) with bleeding from a wide range of sources were treated. Seventy-eight patients had active bleeding (spurting in 50, oozing in 28) and 10 patients had a nonbleeding visible vessel. Initial hemostasis was achieved in all patients with active bleeding. A total of 255 clips were placed (average of 2.9 clips per patient, range of 1-10 clips). Spurting arterial bleeders required more clips on average than oozing bleeders (3.2 versus 2.7); active bleeders required more clips than cases with nonbleeding visible vessels (3.0 versus 2.2). Mean follow-up was 397 +/- 148 days. Recurrent bleeding was observed in 5 patients, all of whom had active bleeding on initial presentation. Re-bleeding was successfully treated with hemoclips in 4 patients and one patient underwent surgery. Clips appeared to be retained well; early clip dislodgement resulted in rebleeding in only 1 patient. No complications resulted from this treatment. Clips did not impair healing of peptic ulcers. We conclude that endoscopic hemoclip placement is a highly effective and safe method for treating nonvariceal gastrointestinal bleeding and deserves comparative studies with other methods of endoscopic hemostasis. PMID- 8491135 TI - Influence of tumor stenosis on the accuracy of endosonography in preoperative T staging of esophageal cancer. AB - The T stage is an important criterion for determining prognosis in esophageal carcinoma. Endosonography, although established as a highly accurate method in preoperative determination of the T stage, may be less reliable in non traversable tumor stenoses. In a comparative prospective study, 41 patients with carcinoma of the esophagus were investigated to determine the role of tumor stenosis on the accuracy of endosonography in preoperative T staging. The results were correlated with the histology of the resected specimen. The overall accuracy in T staging with endosonography was 76%, compared with 49% in computed tomography. T staging results of endosonography were good in easily and non traversable stenoses (92%, 87% respectively), but lower accuracy was obtained in stenoses which could be traversed only with difficulty (46%). Computed tomography was inferior to endosonography in all three groups of patients. The high accuracy of endosonography in non-traversable stenoses might be due to the fact that all tumors were in an advanced stage (T3 or T4). When passage of the echoendoscope proves difficult, the low focal distance between the ultrasonic transducer and tumor may hamper clear visualisation of the wall layers and tumor penetration depth. These limitations of endosonography should stimulate further efforts in improving ultrasonic resolution in these cases. PMID- 8491136 TI - "Endoscopy friendly" resection technique of choledochal cysts. AB - The resection of a choledochal cyst was performed in two patients (22 and 31 years old, both type Todani IVa). Reconstruction of the biliary-intestinal drainage was performed by interposition of a 15 cm jejunal segment between the liver hilum and duodenum. In both patients, hepatico-jejunostomy could be endoscopically evaluated 5-6 months after the operation, showing patent anastomoses without any signs of reflux or cholangitis. PMID- 8491137 TI - EUS: an added test or a replacement for several? PMID- 8491138 TI - Clinical utility of endoscopic ultrasonography for pancreatic tumors. PMID- 8491139 TI - Stomach wall slough and ulcer perforation following endoscopic injection hemostasis with polidocanol. AB - A case is reported of progressive inner layer slough of the stomach antrum resulting in free perforation following endoscopic injection hemostasis of ulcer bleeding using a total of 5 ml polidocanol. This rare complication necessitated gastric resection. Relevant etiologic factors favoring this type of tissue response to endoscopic treatment are discussed. PMID- 8491140 TI - Familial varices of the small and large bowel. AB - Two familial cases of varices confined to the small and the large bowel are reported. Both patients were diagnosed in advanced age because of recurrent intestinal bleeding. The study of the entire gastrointestinal tract revealed an unexpected wide involvement and the primary nature of the varices. Moreover, both patients had coexistent adenomatous polyps. PMID- 8491141 TI - Comment on the letter to the editor of Weissmann D et al. in Endoscopy 1991; 23: 354-355. PMID- 8491142 TI - A new reserve cutting sphincterotome for endoscopic sphincterotomy after Billroth II gastrectomy. PMID- 8491143 TI - Endoscopic hemostasis of a bleeding diverticulum of the sigma with fibrin sealant. PMID- 8491144 TI - Successful endoscopic hemostasis of duodenal variceal bleeding with histoacryl. PMID- 8491145 TI - Endoscopic injection sclerotherapy for esophageal varices in the mid-south district of China. PMID- 8491146 TI - Endoscopic Doppler in diagnosis and therapy of angiodysplasia. PMID- 8491147 TI - An unusual source of gastrointestinal bleeding from the esophagus: two new cases of esophageal visible vessel. PMID- 8491148 TI - Gastrointestinal bleeding complicating transesophageal echocardiography. PMID- 8491149 TI - Ethical guidelines for publications of research. The Council of the Endocrine Society. PMID- 8491150 TI - Infection, thyroid disease, and autoimmunity. AB - The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basis for this review. Classical AITD (i.e. Graves' disease and Hashimoto's thyroiditis) has been shown to be associated with a variety of infectious agents (e.g. Yersinia enterocolitica, retroviruses) while infections of the thyroid gland (e.g. subacute thyroiditis, congenital rubella) have been shown to be associated with thyroid autoimmune phenomena. However, the causative role of infectious agents in AITD has not been definitively demonstrated in humans although AITD can be induced in experimental animals by certain viral infections. Infectious agents may induce thyroid autoimmunity by a variety of diverse mechanisms, such as inducing modifications of self-antigens, mimicking self molecules, inducing polyclonal T cell activation (for example by superantigens), altering the idiotypic network, forming immune complexes, and inducing expression of MHC molecules on thyroid epithelial cells. While indirect data suggesting involvement of the infecting organisms in the pathogenesis of human AITD is abundant, only a limited number of studies have employed direct approaches. Such a direct approach would involve isolation or molecular identification of the potentially infecting organisms from the thyroid gland and the subsequent induction of AITD in an experimental model. PMID- 8491151 TI - Androgen conjugates: physiology and clinical significance. PMID- 8491152 TI - Human growth hormone and human aging. AB - In humans, both aging and GH deficiency are associated with reduced protein synthesis, decreased lean body and bone mass, and increased percent body fat. In healthy individuals, spontaneous and stimulated GH secretion, as well as circulating IGF-I and IGFBP-3 levels, are significantly decreased with advancing age. The extent to which these age-related changes in GH and IGF-I contribute to alterations in body composition and function remains to be elucidated. GH treatment of GH-deficient adults or old men with reduced IGF-I levels with exogenous GH increases plasma IGF-I, nitrogen retention, and lean body mass, decreases percent body fat, and exerts little effect on bone mineral density. Short-term adverse effects of GH therapy have been minimized by using low-dose regimens, but it is still uncertain whether long-term GH supplementation in adult life increases the risk of metabolic abnormalities or malignancy. Administration of GHRH, which has been shown to maintain the pattern of pulsatile GH secretion in old men, may represent another possible physiological approach to therapy. It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc. A great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life. PMID- 8491153 TI - Vitamin D, calcium, and epidermal differentiation. PMID- 8491154 TI - Regulation of the cell cycle by calcium and calmodulin. PMID- 8491155 TI - Estrogen receptors, estradiol, and diethylstilbestrol in early development: the mouse as a model for the study of estrogen receptors and estrogen sensitivity in embryonic development of male and female reproductive tracts. AB - To date, there is no conclusive evidence that ERs are present in preimplantation embryos. There are reports that estrogen is made by the rabbit blastocyst (61), and estrogens have been used to induce implantation in mice (62), but whether estrogens act through ERs in the embryo or in the maternal uterus is not known. ERs may be present in early embryos, but if so, levels are below the methods of detection used thus far. Perhaps with more sensitive immunodetection methods, it may be possible to detect ERs in embryos if they are present. Using PCR, messenger RNA for ER has been detected as early as the oocyte stage in mouse embryos (Q. Hou and J. Gorski, unpublished results). This was confirmed recently by Wu et al. (83a). Figure 7 shows a model for the pattern of ER expression in the developing mouse fetus based on the various reports discussed in this review. ERs are present in the 10-day mouse fetus, possibly in the developing ambisexual reproductive tract. Analysis of seven individual 10-day-old fetuses taken from the same litter showed similar levels of an immunostained protein the size of the ER in each fetus (57). The pattern of expression of ER between implantation and the development of the reproductive tract may be the same in male and female mice. Estrogen, acting through ERs, may be one factor (of many) that determines which cells are destined to be part of the indifferent reproductive tract. We were not able to isolate fetal mouse reproductive tracts at an indifferent stage (day 10) due to their very small size. One way to study ER in the indifferent reproductive tract would be to examine these tissues in a larger animal, such as the bovine, using similar immunodetection methods. The distribution of ER in the fetal mouse reproductive tract on fetal days 13 (before sexual differentiation) and 15 (initiation of sexual differentiation) is similar in males and females (71, 72). Thus, estrogen does not appear to be responsible for the initiation of sexual differentiation. Early experiments by Jost (41) showed that removal of the gonad from male or female rabbit fetuses resulted in the female phenotype, which lent weight to the hypothesis that ovarian hormones are not critical in the development of the female phenotype, whereas testicular hormones are essential for the development of the male phenotype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8491156 TI - Genetic and nongenetic determinants of regional fat distribution. AB - The role of inherited and nongenetic factors in individual differences observed in the level of sc fat on the trunk and abdominal areas and in the abdominal visceral deposit is reviewed. First, the metabolic and clinical implications of variation in body fat topography are summarized. Second, the results of genetic epidemiology studies on the heritability and other evidence for a role of the genotype in the amount of truncal-abdominal sc fat and abdominal visceral fat are reviewed. Third, the impact of total body fat, age, and gender on regional fat distribution is highlighted. Fourth, adipose tissue lipoprotein lipase activity is considered as a determinant of fat topography, with a discussion of site and gender differences, the effects of steroid hormones, and evidence from genetic epidemiology. Fifth, the contribution of adipose tissue lipolysis is reviewed with an emphasis on the various regulatory factors of the lipolytic pathways including catecholamines, insulin, adenosine, steroids, and other modulators. The role of lipolytic characteristics on fat topography is further assessed by considering changes with age, differences between men and women, effects of excess body fat, and data from heritability studies. Although the study of regional variation of in vitro adipose tissue metabolism has provided valuable information, a better understanding of variation in fat topography and of the role played by adipose tissue in the regulation of whole body carbohydrate and lipid metabolism will likely require extensive in situ and in vivo investigations. Sixth, as enlargement of a specific fat deposit is associated with increases in fat cell size and number, these topics are considered with an emphasis on the role of adipose cell differentiation. Seventh, the importance of blood levels of sex steroids and glucocorticoids for regional fat distribution is discussed. Then, a unifying hypothesis, defined as the hypothalamic arousal and neuroendocrine dysregulation model, is briefly described. Finally, the issue of whether body fat distribution can be altered by caloric restriction or regular exercise is addressed. PMID- 8491157 TI - The role of thyroid hormones in prenatal and neonatal neurological development- current perspectives. PMID- 8491158 TI - Small trials rather than large observational studies in nutritional epidemiology. PMID- 8491159 TI - Lactoferrin, lactoferrin receptors and iron metabolism. PMID- 8491160 TI - Validation of a food frequency questionnaire for assessing dietary intake in a study of coronary heart disease risk factors in children. AB - A food frequency questionnaire (FFQ) was designed and validated for use in an epidemiological survey measuring coronary heart disease risk factors in British children. The questionnaire asked about the frequency of children's consumption of 35 food items over the previous month and was completed by parents/guardians. Food items represented a range of food groups from which children may eat, with emphasis on foods with a high fat and fibre content. The questionnaire was validated against 14 daily recalls of consumption, using the same food list as the FFQ. The sample consisted of 272 children, aged 5-11 years, The response rate for the FFQ was 92% and for the recall, 82% in the first week and 66% in the second week. The level of agreement between the FFQ and the recall was measured by calculating (McGinnis JM & Nestle M, 1989, Am. J. Clin. Nutr. 49, 23-28) the median difference between results from the two methods and (Willett WC (ed.), 1990, Nutritional epidemiology, ch. 15; Oxford University Press) the percentage of children classified by FFQ to within +/- 1 day per week of the recall. Median differences between individual items on the questionnaire and the recall were < or = 0.5 days for 91% of items and equal to 1 day for the remainder. The percentage agreement to within +/- 1 day per week between frequencies reported in the two methods ranged from 99.8% for lamb to 46.8% for low-fibre cereal. Better agreement was found for food items representative of fat intake than those of fibre intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491161 TI - Effect of regular consumption of oily fish compared with white fish on chronic plaque psoriasis. AB - The influence of dietary advice on the severity of chronic plaque psoriasis was studied in 18 patients. Medication was standardized in all patients who were advised to eat 170 g white fish daily for a 4 week run-in period. Then the patients were randomized either to continue with the white fish diet or to substitute 170 g oily fish daily for 6 weeks. At the end of this second period the diets were reversed for a further 6 weeks. The oily fish but not the white fish diet led to a modest clinical improvement (11% and 15%, P < 0.01) which was accompanied by a rise in plasma eicosapentaenoic acid (20:5n-3) concentrations. It is concluded that dietary advice to increase the daily intake of oily fish is a useful adjunct in the treatment of psoriasis. The fish that should be recommended include mackerel, sardine, salmon, pilchard, kipper and herring. PMID- 8491162 TI - The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. AB - Eight healthy male volunteers supplemented their normal diet with 10-15 g/d of a fish oil supplement (MaxEPA) to provide 1.4-4.2 g/d of eicosapentaenoic acid (EPA; C20:5 n-3) for a period of 12 weeks. Blood samples were taken at weeks 0, 2 and 12 and the fatty acid compositions of the phospholipids of plasma, platelets, neutrophils, monocytes and T- and B-lymphocytes were determined. In all instances the level of EPA increased significantly (P < 0.05) by 2 weeks and remained so without a further increase for the ensuing 10 weeks. Beyond that, few consistent patterns in fatty acid composition were observed. Arachidonic acid (C20:4 n-6) fell significantly (P < 0.05) in plasma, platelets, neutrophils and T- and B lymphocytes, but generally tended to do so only by week 12. Given the wide variability in the half-life of these cells (minutes for neutrophils, months for lymphocytes) it is evident that uptake of plasma EPA occurs by phospholipid exchange into preformed mature cells and does not require incorporation during cell genesis. PMID- 8491163 TI - Fatty acid compositions of inositol and choline phospholipids of breast tumours and normal breast tissue. AB - The fatty acid compositions of the -choline and -inositol phospholipids of breast tumours of women undergoing surgery for treatment of breast disease (malignant n = 12; benign n = 10) and normal breast tissue of women undergoing breast reduction surgery (n = 6) were determined. The fatty acid compositions of erythrocyte phospholipids were also determined in the same subjects and in an additional number of normal healthy volunteers (n = 16). Levels of oleic acid were lower in both phospholipid fractions of erythrocytes of women with breast disease and in the phosphatidylcholine fraction of breast tumours compared with normal breast tissue. Significantly higher levels of linoleic acid were found in erythrocytes of tumour-bearing subjects and a similar trend was evident in the phosphatidylcholine fraction of tumour compared with normal breast tissues. Conversely, lower levels of two of the products of linoleic acid chain elongation and desaturation, dihomogamma-linolenic and arachidonic acids, were found in the erythrocyte phospholipids of tumour-bearing subjects and in the choline phospholipids of breast tumour tissues. These data suggest that in women with breast disease, there may be inhibition of 6-desaturase, and enhanced activity of 9-desaturase, enzymes which play an important role in determining membrane phospholipid fatty acid composition. This pattern of altered fatty acid composition characteristic of erythrocyte phospholipids of tumour-bearing subjects and phosphatidylcholine of breast tumour tissue was less evident in the case of the breast tumour phosphatidylinositol in which differences other than those described were seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491164 TI - Complex carbohydrates in the prevention of nocturnal hypoglycaemia in diabetic children. AB - In order to prevent nocturnal hypoglycaemia in patients with insulin-dependent diabetes mellitus with complex carbohydrates a pilot-study was designed with nine children with ages of 9-18 years. The children were admitted twice to the hospital (control and test) and remained the evening, night and morning the following day. The standard evening snack, given on the control day, was replaced on the test day by a test snack which contained a solution of uncooked cornstarch as a source of complex carbohydrates. The carbohydrate content of the test snack was maintained but did not contain mono- and disaccharides. Blood samples were collected and when the child had blood glucose concentrations of < or = 3.0 mmol/l or showed clinical symptoms of impending hypoglycaemia, intervention occurred with extra carbohydrates. Six out of nine children needed intervention after the standard snack (blood glucose concentrations were 1.8, 2.7, 3.0, 3.6 and 3.7 mmol/l). After the test snack this was four out of nine (blood glucose concentrations were 2.3, 2.6, 3.2 and 3.2). Three children needed a second intervention after the standard snack versus two after the test snack. One child needed a third intervention after the standard snack. The time of intervention ranged from 11 p.m. to 4 a.m. and from 10 p.m. to 12 a.m., respectively, on the day of the standard and test snack. Raw cornstarch, as a source of complex carbohydrates, did not prevent nocturnal hypoglycaemia in the dose used but blood glucose levels dropped more slowly than those after the standard snack.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491165 TI - Effect of circadian variation in energy expenditure, within-subject variation and weight reduction on thermic effect of food. AB - Thermic effect of food (TEF) studies give conflicting answers to research questions and in many cases data from one laboratory to another is not comparable because of the utilization of different experimental methods. Likewise, how weight reduction affects measurement of TEF is controversial. Two studies were conducted on how TEF affects energy expenditure. The first study examined how resting energy expenditure (REE) measurements can affect TEF studies and how much within-subject variation is found in TEF studies. The TEF of a standard meal was measured in six subjects for 6.5 h on three different occasions by indirect calorimetry. REE was measured on each subject for 1 h before the meal was given on each measurement occasion. On a separate day, the energy expenditure was measured on each subject during the same time period as the TEF measurement, but without any food given to determine if a circadian increase in REE over the time period of the measurement was observed. We found no circadian increase in energy expenditure during the 6.5 h of the REE study. While the within-subject variation in REE (four measurements) had an average coefficient of variation of 5.2% (range 2.4-8.5%), the coefficient of variation of the TEF measured (three measurements) was 26.4% (range 13.6-50.9). In the second study, REF and the TEF were measured before and after weight reduction in moderately overweight adult women. Nine women weighing between 62.1 and 84.7 kg lost an average of 7.3 kg while on a reduced calorie, low fat diet for between 12 and 14 weeks. After weight reduction, the average REE of these subjects decreased by 8.8% or 515 kJ (123 kcal)/24 h. The TEF of these nine women was measured for 6.5 h before and after weight reduction using 16 oz of Sustacal, 2008 kJ (480 kcal). Before weight reduction the thermic effect of Sustacal was 264 kJ (63 kcal) or 13% of calories consumed, and after weight reduction it was 251 kJ (60 kcal) or 12.5% of calories consumed. We did not find the TEF to be lower than expected in these subjects before weight reduction, since TEF is often reported to be around 10% of energy consumed, and it was not changed after weight reduction. PMID- 8491166 TI - Structural features of resistant starch at the end of the human small intestine. AB - Structural features of in vivo resistant starch were assessed using the ileal contents of four humans. Two of the latter were collected by ileostomy after ingestion of bean flakes or potato flakes and the other two were collected by an intubation technique after ingestion of retrograded high-amylose maize starch or complexed high-amylose maize starch. The degree of polymerizations (DP), solubility and crystallinity were assessed. For all samples, starch fractions which escaped digestion in the small intestine were composed of three populations of alpha-glucans with proportions differing according to the substrate. Small quantities of oligosaccharides made up the first population, illustrating a limitation of absorption in the small intestine. The second population, the main resistant fraction, was comprised of retrograded amylose of mean DPn of about 35 glucose units with a melting temperature at 150 degrees C and exhibiting a B-type pattern. Finally high molecular weight semi-crystalline alpha-glucans were attributed to fragments of starch. This study showed that some potentially digestible starch could reach the colon and crystalline fractions constituted only part of the starch that escaped digestion in the human small intestine. PMID- 8491167 TI - Translocation of cytoplasm and nucleus to fungal penetration sites is associated with depolymerization of microtubules and defence gene activation in infected, cultured parsley cells. AB - We describe a novel system of reduced complexity for analysing molecular plant fungus interactions. The system consists of suspension-cultured parsley (Petroselinum crispum) cells infected with a phytopathogenic fungus (Phytophthora infestans) which adheres to a coated glass plate and thus immobilizes the plant cells for live microscopy. Conventional light and electron microscopy as well as time-lapse video microscopy confirmed the virtual identity of fungal infection structures and of several characteristic early plant defence reactions in the cultured cells and whole-plant tissue. Using this new system to approach previously unresolved questions, we made four major discoveries: (i) rapid translocation of plant cell cytoplasm and nucleus to the fungal penetration site was associated with local depolymerization of the microtubular network; (ii) the directed translocation was dependent on intact actin filaments; (iii) a typical plant defence-related gene was activated in the fungus-invaded cell; and (iv) simultaneous activation of this gene in adjacent, non-invaded cells did not require hypersensitive death of the directly affected cell. PMID- 8491168 TI - Phosphorylation and dephosphorylation affect functional characteristics of chloroplast and etioplast transcription systems from mustard (Sinapis alba L.). AB - Chloroplast and etioplast RNA polymerase preparations each consist of a multi subunit core and a set of three sigma-like transcription factors, SLF67, SLF52 and SLF29. Despite this structural similarity, the enzymes from either plastid type are functionally distinct, as is reflected by their different promoter usage and the tight core-SLF association in the etioplast but not the chloroplast holoenzyme. We tested whether these differences are related to phosphorylation. Treatment of the chloroplast enzyme with protein kinase converted it to an etioplast-type form and vice versa, treatment of the etioplast enzyme with phosphatase generated chloroplast-type properties. Although both the core enzyme and the SLF polypeptides were phosphorylation targets, only the SLFs seem to confer plastid-type-specific DNA binding characteristics. Methylation interference and DNase I footprint patterns in the psbA promoter region were found to correlate with the phosphorylation state of the chloroplast and etioplast enzymes. PMID- 8491169 TI - Crystal structure of a flavoprotein related to the subunits of bacterial luciferase. AB - The molecular structure of the luxF protein from the bioluminescent bacterium Photobacterium leiognathi has been determined by X-ray diffraction techniques and refined to a conventional R-factor of 17.8% at 2.3 A resolution. The 228 amino acid polypeptide exists as a symmetrical homodimer and 33% of the monomer's solvent-accessible surface area is buried upon dimerization. The monomer displays a novel fold that contains a central seven-stranded beta-barrel. The solvent exposed surface of the monomer is covered by seven alpha-helices, whereas the dimer interface is primarily a flat surface composed of beta-strands. The protein monomer binds two molecules of flavin mononucleotide, each of which has C6 of the flavin isoalloxazine moiety covalently attached to the C3' carbon atom of myristic acid. Both myristyl groups of these adducts are buried within the hydrophobic core of the protein. One of the cofactors contributes to interactions at the dimer interface. The luxF protein displays considerable amino acid sequence homology with both alpha- and beta-subunits of bacterial luciferase, especially the beta-subunit. Conserved amino acid residues shared between luxF and the luciferase subunits cluster predominantly in two distinct regions of the luxF protein molecule. These homologous regions in the luciferase subunits probably share a three-dimensional fold similar to that of the luxF protein. PMID- 8491170 TI - Inherent asymmetry of the structure of F1-ATPase from bovine heart mitochondria at 6.5 A resolution. AB - ATP synthase, the assembly which makes ATP in mitochondria, chloroplasts and bacteria, uses transmembrane proton gradients generated by respiration or photosynthesis to drive the phosphorylation of ADP. Its membrane domain is joined by a slender stalk to a peripheral catalytic domain, F1-ATPase. This domain is made of five subunits with stoichiometries of 3 alpha: 3 beta: 1 gamma: 1 delta: 1 epsilon, and in bovine mitochondria has a molecular mass of 371,000. We have determined the 3-dimensional structure of bovine mitochondrial F1-ATPase to 6.5 A resolution by X-ray crystallography. It is an approximately spherical globule 110 A in diameter, on a 40 A stem which contains two alpha-helices in a coiled-coil. This stem is presumed to be part of the stalk that connects F1 with the membrane domain in the intact ATP synthase. A pit next to the stem penetrates approximately 35 A into the F1 particle. The stem and the pit are two examples of the many asymmetric features of the structure. The central element in the asymmetry is the longer of the two alpha-helices in the stem, which extends for 90 A through the centre of the assembly and emerges on top into a dimple 15 A deep. Features with threefold and sixfold symmetry, presumed to be parts of homologous alpha and beta subunits, are arranged around the central rod and pit, but the overall structure is asymmetric. The central helix provides a possible mechanism for transmission of conformational changes induced by the proton gradient from the stalk to the catalytic sites of the enzyme. PMID- 8491171 TI - The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments. AB - The crystal structure of EcoRV endonuclease has been determined at 2.5 A resolution and that of its complexes with the cognate DNA decamer GGGATATCCC (recognition sequence underlined) and the non-cognate DNA octamer CGAGCTCG at 3.0 A resolution. Two octamer duplexes of the non-cognate DNA, stacked end-to-end, are bound to the dimeric enzyme in B-DNA-like conformations. The protein--DNA interactions of this complex are prototypic for non-specific DNA binding. In contrast, only one cognate decamer duplex is bound and deviates considerably from canonical B-form DNA. Most notably, a kink of approximately 50 degrees is observed at the central TA step with a concomitant compression of the major groove. Base-specific hydrogen bonds between the enzyme and the recognition base pairs occur exclusively in the major groove. These interactions appear highly co operative as they are all made through one short surface loop comprising residues 182-186. Numerous contacts with the sugar phosphate backbone extending beyond the recognition sequence are observed in both types of complex. However, the total surface area buried on complex formation is > 1800 A2 larger in the case of cognate DNA binding. Two acidic side chains, Asp74 and Asp90, are close to the reactive phosphodiester group in the cognate complex and most probably provide oxygen ligands for binding the essential cofactor Mg2+. An important role is also indicated for Lys92, which together with the two acidic functions appears to be conserved in the otherwise unrelated structure of EcoRI endonuclease. The structural results give new insight into the physical basis of the remarkable sequence specificity of this enzyme. PMID- 8491172 TI - The three-dimensional NMR-solution structure of the polypeptide fragment 195-286 of the LFB1/HNF1 transcription factor from rat liver comprises a nonclassical homeodomain. AB - The three-dimensional backbone fold of a polypeptide fragment from the rat LFB1/HNF1 transcription factor was determined by nuclear magnetic resonance (NMR) spectroscopy in solution. This fragment contains an amino acid sequence that is approximately 22% homologous to the well known homeodomains, but which contains 81 amino acid residues as compared with 60 residues in 'typical' homeodomains. For the present studies we used a recombinant 99 amino acid polypeptide containing this sequence in positions 10-90, which was uniformly labelled with 15N and also doubly labelled with 15N and 13C. The NMR structure of this polypeptide contains three alpha-helices comprising the residues 18-29, 36-50 and 71-84, a loop formed by residues 30-35, and a long stretch of non-regular secondary structure linking the second and third helices. The relative location and orientation of the helices is very similar to that in the Antennapedia (Antp) homeodomain structure, despite the fact that helix II is elongated by about one turn. This confirms a recently advanced hypothesis based on sequence comparisons that this polypeptide segment of LFB1/HNF1 might represent a homeodomain-like structural element. The helix-turn-helix motif, which has been shown to comprise the DNA recognition helix in the Antp homeodomain, can readily be recognized in the LFB1/HNF1 homeodomain, in spite of an extensive modification of the primary structure. The two residues of the tight turn in the Antp homeodomain are replaced by a 23 residue linker region between the two helices in LFB1/HNF1, which bulges out from the rest of the molecule and thus enables the formation of a non-classical helix--turn--helix motif. PMID- 8491173 TI - The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding. AB - The transcription factor LFB1/HNF1 from rat liver nuclei is a 628 amino acid protein that functions as a dimer binding to the inverted palindrome GTTAATN ATTAAC consensus site. We have crystallized a 99 residue protein containing the homeodomain portion of LFB1, and solved its structure using X-ray diffraction data to 2.8 A resolution. The topology and orientation of the helices is essentially the same as that found in the engrailed, MAT alpha 2 and Antennapedia homeodomains, even though the LFB1 homeodomain contains 21 more residues. The 21 residue insertion is found in an extension of helix 2 and consequent lengthening of the connecting loop between helix 2 and helix 3. Comparison with the engrailed homeodomain-DNA complex indicates that the mode of interaction with DNA is similar in both proteins, with a number of conserved contacts in the major groove. The extra 21 residues of the LFB1 homeodomain are not involved in DNA binding. Binding of the LFB1 dimer to a B-DNA palindromic consensus sequence requires either a conformational change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA. PMID- 8491174 TI - Focal exocytosis by eosinophils--compound exocytosis and cumulative fusion. AB - We have investigated the granule fusion events during exocytosis in horse eosinophils by time-resolved patch-clamp capacitance measurements. Stimulation with intracellular GTP gamma S leads to a stepwise capacitance increase by 4.0 +/ 0.9 pF. At GTP gamma S concentrations < 20 microM the step size distribution is in agreement with the granule size distribution in resting cells. Above 80 microM the number of steps is reduced and very large steps occur. The total capacitance increase, however, is unaffected. These results show that at high GTP gamma S concentrations granule--granule fusion occurs inside the cell forming large compound granules, which then fuse with the plasma membrane (compound exocytosis). The electrical equivalent circuit of the cell during degranulation indicates the formation of a degranulation sac by cumulative fusion events. Fusion of the first granule with the plasma membrane induces fusion of further granules with this granule directing the release of all the granular material to the first fusion pore. The physiological function of eosinophils is the killing of parasites. Compound exocytosis and cumulative fusion enable the cells to focus the release of cytotoxic proteins to well defined target regions and prevent uncontrolled diffusion of this material, which would damage intact host cells. PMID- 8491175 TI - V-region directed selection in differentiating B lymphocytes. AB - We here analyse the repertoire of VH7183 rearrangements isolated from different stages of B cell differentiation in adult mice. The nucleotide sequence analyses of VH7183-D-JH rearrangements derived from large pre-B cells (B220+, mu-), small pre-B cells (B220+, mu-) and mature B cells (B220+, mu+) isolated from adult bone marrow revealed a sequential accumulation, among functional rearrangements, of D segments of the FL16 family and a depletion of D segments using the second and the third reading frame (RF). One member (VH7183.1) of the VH7183 gene family was utilized in 60-80% of the rearrangements of all populations analysed. In neonates the majority of the rearrangements utilizing this gene was found to be functional. In contrast, > 96% of the VH7183 rearrangements isolated from adult spleen were non-functional. These data provide evidence for cellular selection of VH regions acting at different points of the B cell differentiation pathway and at the transition of B cells from the bone marrow to the periphery. PMID- 8491176 TI - A novel gene product associated with mu chains in immature B cells. AB - A previously unreported B cell specific gene, which we have named 8HS-20, was isolated from the cDNA library of a pre-B cell clone by subtraction and differential hybridization. This gene is selectively expressed as a 0.75 kb transcript in pre-B and bone marrow-derived B cell lines; a transcript of the same size is also found in bone marrow and, albeit at low levels, in spleen. The deduced amino acid sequence of the 8HS-20 cDNA displayed homology to a B cell specific gene, VpreB-1, and to members of the immunoglobulin supergene family including V lambda, V kappa, VH, TCRV alpha, V beta and CD8. Biochemical analysis using purified antiserum against 8HS-20 oligopeptides indicates that the gene encodes proteins with mol. wts of 13.5, 14, 15.5 and 16 kDa, which associate with mu chains in pre-B cell lines, and that these molecules are expressed concomitantly with VpreB-1 and lambda 5 gene products in the same cell lines. PMID- 8491177 TI - Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. AB - Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta 1 cDNA placed under the control of regulatory elements of the pregnancy responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the development and function of the mammary gland. PMID- 8491178 TI - Generation of structural and functional diversity in furin-like proteins in Drosophila melanogaster by alternative splicing of the Dfur1 gene. AB - To investigate whether or not alternative splicing might be a mechanism by which in Drosophila melanogaster diversity is generated in endoproteases of the novel eukaryotic family of subtilisin-like proprotein processing enzymes, we determined structural and functional characteristics of the Dfur1 gene. Northern blot analysis revealed Dfur1 transcripts of 7.6, 6.5, 4.5 and 4.0 kb. By comparative nucleotide sequence analysis of Dfur1 genomic and cDNA clones, 10 coding exons were identified and, together with Northern blot analysis using exon-specific probes, evidence was obtained that the four transcripts are generated by alternative splicing and polyadenylation. The apparently complete open reading frames of three Dfur1 cDNAs revealed that these coded for three furin-like proteins, Dfurin1 (892 residues), Dfurin1-CRR (1101 residues) and Dfurin1-X (1269 residues), which possessed common but also unique structural domains. These various isoforms of furin in Drosophila were characterized in gene transfer studies using immunoprecipitation analysis. Differential expression of Dfur1 transcripts was found in Northern blot analysis of RNA from various developmental stages of Drosophila. RNA in situ hybridization experiments revealed that the Dfurin1-X and Dfurin1-CRR isoforms are expressed in non-overlapping sets of tissues during Drosophila embryogenesis. In gene transfer experiments in which the Dfurin1, Dfurin1-CRR and Dfurin1-X proteins were expressed at high levels together with the precursor of the beta A-chain of activin-A, a member of the transforming growth factor beta (TGF beta) superfamily, or the precursor of von Willebrand factor, all three proteins appeared capable of processing these substrates. Our studies indicate that the Dfur1 gene encodes structurally different subtilisin-like proprotein processing enzymes with distinct physiological functions in Drosophila. PMID- 8491179 TI - Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle. AB - A search for inhibitors of urokinase-type plasminogen activator (uPA) in the male and female murine genital tracts revealed high levels of a uPA ligand in the seminal vesicle. This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes. A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs. PN-I is synthesized in the epithelium of the seminal vesicle, as determined by in situ hybridization, and is secreted in the lumen of the gland. PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control. PMID- 8491180 TI - A single EGF-like motif of laminin is responsible for high affinity nidogen binding. AB - A major nidogen binding site of mouse laminin was previously localized to about three EGF-like repeats (Nos 3-5) of its B2 chain domain III [M. Gerl et al. (1991) Eur. J. Biochem., 202, 167]. The corresponding cDNA was amplified by polymerase chain reaction and inserted into a eukaryotic expression vector tagged with a signal peptide. Stably transfected human kidney cell clones were shown to process and secrete the resulting fragment B2III3-5 in substantial quantities. It possessed high binding activity for recombinant nidogen in ligand assays, with an affinity comparable with that of authentic laminin fragments. In addition, complexes of B2III3-5 and nidogen could be efficiently converted into a covalent complex by cross-linking reagents. Proteolytic degradation of the covalent complex demonstrated the association of B2III3-5 with a approximately 80 residue segment of nidogen domain G3 to which laminin binding has previously been attributed. The correct formation of most of the 12 disulfide bridges in B2III3-5 was indicated from its protease resistance and the complete loss of cross reacting epitopes as well as of nidogen-binding activity after reduction and alkylation. Smaller fragments were prepared by the same recombinant procedure and showed that combinations of EGF-like repeats 3-4 and 4-5 and the single repeat 4 but not repeats 3 or 5 possess full nidogen-binding activity. This identifies repeat 4 as the only binding structure. The sequence of repeat 4 is well conserved in the human and in part in the Drosophila laminin B2 chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491181 TI - Bacterial internalization mediated by beta 1 chain integrins is determined by ligand affinity and receptor density. AB - Binding of bacteria to beta 1 chain integrin receptors results in either bacterial adherence or uptake by cultured cells (Isberg, 1991). In this report we show that Staphylococcus aureus coated with high affinity ligands for the beta 1 chain integrin family can be internalized efficiently, whereas bacteria coated with low affinity ligands are poorly internalized. Overproduction of the alpha 5 beta 1 integrin increased the efficiency of bacterial internalization, indicating that the uptake efficiency is directly related to the level of expression of the receptor. By using latex beads or S. aureus coated with mAbs directed against the alpha 5 beta 1 integrin, a roughly semi-logarithmic correlation was observed between the affinity of the receptor-ligand interaction and the rate of bacterial internalization. Evidence is presented that high affinity binding of the bacterium allows the microorganism to compete efficiently with receptor-ligand interactions at the basolateral surface of the cell. PMID- 8491182 TI - Strategies for differential sensory responses mediated through the same transmembrane receptor. AB - Trg mediates chemotaxis of Escherichia coli to galactose and ribose by recognition of respective, sugar-occupied binding proteins. Although both attractants act through one transmembrane receptor, maximal response is approximately 50% greater to ribose. This phenomenon was investigated by mutational analysis of a 20-residue segment of Trg implicated in ligand interaction and signalling. Among 17 defective receptors, responses to the two chemoattractants were reduced equivalently for seven and differentially for 10, in some cases reversing the preference order. Mutational substitutions with equivalent effects occurred throughout the segment, but those with a greater effect on galactose or ribose response were segregated to the amino-terminal two thirds or the carboxy-terminal one-third, respectively, a segregation corresponding in large part to a functional division based on signalling phenotypes. A model for binding protein-mediated recognition revealed two strategies for differential responses. The wild-type preference for ribose probably reflects a balance of receptor affinities and a limiting supply of binding proteins. Mutants with reversed preference probably have differentially reduced receptor affinities and those with an accentuated ribose preference probably have altered signalling abilities. Two-step recognition of ligand allows functional separation of detection and response. PMID- 8491183 TI - Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. AB - A variety of eukaryotic cell surface proteins, including the variant surface glycoproteins of African trypanosomes, rely on a covalently attached lipid, glycosylphosphatidylinositol (GPI), for membrane attachment. GPI anchors are synthesized in the endoplasmic reticulum by stepwise glycosylation of phosphatidylinositol (via UDP-GlcNAc and dolichol-P-mannose) followed by the addition of phosphoethanolamine. The experiments described in this paper are aimed at identifying the biosynthetic origin of the terminal phosphoethanolamine group. We show that trypanosome GPIs can be labelled via CDP-[3H]ethanolamine or [beta-32P]CDP-ethanolamine in a cell-free system, indicating that phosphoethanolamine is acquired en bloc. In pulse-chase experiments with CDP [3H]ethanolamine we show that the GPI phosphoethanolamine is not derived directly from CDP-ethanolamine, but instead from a relatively stable metabolite, such as phosphatidylethanolamine (PE), generated from CDP-ethanolamine in the cell-free system. To test the possibility that PE is the immediate donor of the GPI phosphoethanolamine moiety, we describe metabolic labelling experiments with [3H]serine and show that GPIs can be labelled in the absence of detectable radiolabelled CDP-ethanolamine, presumably via [3H]PE generated from [3H]phosphatidylserine (PS). The data support the proposal that the terminal phosphoethanolamine group in trypanosome GPIs is derived from PE. PMID- 8491184 TI - A novel role for RhoGDI as an inhibitor of GAP proteins. AB - RhoGDI inhibits guanine nucleotide dissociation from post-translationally processed Rho and Rac proteins but its biochemical role in vivo is unknown. We show here that N-terminal effector site mutations in the Rac protein do not compromise its interaction with RhoGDI and that, whilst geranylgeranylation and AAX proteolysis of the C-terminal CAAX motif of Rac1 and RhoA are required for efficient interaction with RhoGDI, methylesterification of the C-terminal cysteine residue is not required. In vitro, RhoGDI can form stable complexes with Rho and Rac proteins in both the GTP and GDP bound states. Furthermore the Rac GTP--RhoGDI complex is resistent to the action of recombinant RhoGAP and recombinant BCR. Thus GDI, by complexing with Rac-GTP and preventing GAP stimulated GTP hydrolysis, may allow transit of the activated form of the Rac protein between physically separated activator and effector proteins in the cell. PMID- 8491185 TI - Characterization of full-length neurofibromin: tubulin inhibits Ras GAP activity. AB - Full-length neurofibromin is a GTPase activating protein (GAP) for the Ras proto oncogene product. Regulation of neurofibromin activity therefore has important implications for cell growth. Neurofibromin co-purifies with tubulin when expressed in insect cells. The interaction between neurofibromin and tubulin is sensitive to the microtubule depolymerizing agent colchicine. Neurofibromin GAP activity is inhibited even at low concentrations of tubulin. However, maximal inhibition of GAP activity is only approximately 70%, suggesting that the neurofibromin-tubulin complex retains residual GAP activity. This decreased activity is reflected by a 4-fold decrease in its affinity for Ras. A truncated mutant of neurofibromin with reduced sensitivity to tubulin localizes some tubulin-binding determinants to an 80 residue segment immediately N-terminal to the GAP-related domain. Since tubulin is an abundant protein in eukaryotic cells, the tubulin-neurofibromin interaction may regulate the Ras signalling pathway. PMID- 8491186 TI - The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. AB - GRB2, a small protein comprising one SH2 domain and two SH3 domains, represents the human homologue of the Caenorhabditis elegans protein, sem-5. Both GRB2 and sem-5 have been implicated in a highly conserved mechanism that regulates p21ras signalling by receptor tyrosine kinases. In this report we show that in response to insulin, GRB2 forms a stable complex with two tyrosine-phosphorylated proteins. One protein is the major insulin receptor substrate IRS-1 and the second is the SH2 domain-containing oncogenic protein, Shc. The interactions between GRB2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH2 domain of GRB2 to phosphotyrosines on both IRS-1 and Shc. Although GRB2 associates with IRS-1 and Shc, it is not tyrosine-phosphorylated after insulin stimulation, implying that GRB2 is not a substrate for the insulin receptor. Furthermore, we have identified a short sequence motif (YV/IN) present in IRS-1, EGFR and Shc, which specifically binds the SH2 domain of GRB2 with high affinity. Interestingly, both GRB2 and phosphatidylinositol-3 (PI-3) kinase can simultaneously bind distinct tyrosine phosphorylated regions on the same IRS-1 molecule, suggesting a mechanism whereby IRS-1 could provide the core for a large signalling complex. We propose a model whereby insulin stimulation leads to formation of multiple protein--protein interactions between GRB2 and the two targets IRS-1 and Shc. These interactions may play a crucial role in activation of p21ras and the control of downstream effector molecules. PMID- 8491187 TI - Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation. AB - The non-transmembrane protein tyrosine phosphatase, PTP1B, comprises 435 amino acids, of which the C-terminal 114 residues have been implicated in controlling both localization and function of this enzyme. Inspection of the sequence of the C-terminal segment reveals a number of potential sites of phosphorylation. We show that PTP1B is phosphorylated on seryl residues in vivo. Increased phosphorylation of PTP1B is seen to accompany the transition from G2 to M phase of the cell cycle. Two major tryptic phosphopeptides appear in two-dimensional maps of PTP1B from mitotic cells. One of these comigrates with the peptide generated following phosphorylation of PTP1B in vitro at Ser386 by the mitotic protein Ser/Thr kinase p34cdc2:cyclin B. The site of phosphorylation that is responsible for the pronounced retardation in the electrophoretic mobility of PTP1B from mitotic cells has been identified by site directed mutagenesis as Ser352. The identify of the kinase responsible for this modification is presently unknown. We also show that stimulation of HeLa cells with the phorbol ester TPA enhances phosphorylation of PTP1B. Two dimensional phosphopeptide mapping reveals that the bulk of the phosphate is in a single tryptic peptide. The site, identified as Ser378, is also the site of phosphorylation by protein kinase C (PKC) in vitro. Thus the TPA-stimulated phosphorylation of PTP1B in vivo appears to result directly from phosphorylation by PKC. The effect of phosphorylation on the activity of PTP1B has been examined in immunoprecipitates from TPA-treated and nocodazole-arrested cells. TPA treatment does not appear to affect activity directly, whereas the activity of PTP1B from nocodazole-arrested cells is only 70% of that from asynchronous populations. PMID- 8491188 TI - A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. AB - Both cyclins A and B associate with and thereby activate cyclin-dependent protein kinases (cdks). We have investigated which component in the cyclin-cdk complex determines its substrate specificity. The A- and B-type cyclin-cdk complexes phosphorylated histone H1 and their cyclin subunits in an indistinguishable manner, irrespective of the catalytic subunit, p33cdk2 or p34cdc2. In contrast, only the cyclin A-cdk complexes phosphorylated the Rb-related p107 protein in vitro. Likewise, binding studies revealed that cyclin A-cdk complexes bound stably to p107 in vitro, whereas cyclin B-cdk complexes did not detectably associate with p107, under identical assay conditions. Binding to p107 required both cyclin A and a cdk as neither subunit alone bound to p107. These results demonstrate that although the kinase subunit provides a necessary component for binding, it is the cyclin subunit that plays the critical role in targeting the complex to p107. Finally, we show that the cyclin A-p33cdk2 complex phosphorylated p107 in vitro at most of its sites that are also phosphorylated in human cells, suggesting that the cyclin A-p33cdk2 complex is a major kinase for p107 in vivo. PMID- 8491189 TI - Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. AB - It is widely assumed that degradation of mitotic cyclins causes a decrease in mitotic cdc2/CDC28 kinase activity and thereby triggers the metaphase to anaphase transition. Two observations made on the budding yeast Saccharomyces cerevisiae are inconsistent with this scenario: (i) anaphase occurs in the presence of high levels of kinase in cdc15 mutants and (ii) overproduction of a B-type mitotic cyclin causes arrest not in metaphase as previously reported but in telophase. Kinase destruction is therefore implicated in the exit from mitosis rather than the entry into anaphase. The behaviour of esp1 mutants shows in addition that kinase destruction can occur in the absence of anaphase completion. The execution of anaphase and the destruction of CDC28 kinase activity therefore appear to take place independently of one another. PMID- 8491190 TI - Two novel protein kinase C-related genes of fission yeast are essential for cell viability and implicated in cell shape control. AB - Two novel protein kinase C (PKC)-like genes, pck1+ and pck2+ were isolated from fission yeast by PCR. Both contain common domains of PKC-related molecules, but lack a putative Ca(2+)-binding domain so that they may belong to the nPKC group. Gene disruption of pck1+ and pck2+ establishes that they share an overlapping essential function for cell viability. Cells of a single pck2 deletion display severe defects in cell shape; they are irregular and sometimes pear-like instead of cylindrical. In contrast, the induced overexpression of pck2+ is lethal, producing multiseptated and branched cells. These results suggest that fission yeast PKC-like genes are involved in the polarity of cell growth control. We show that pck2 is allelic to sts6, a locus we have previously identified by its supersensitivity to staurosporine, a potent protein kinase inhibitor [Toda et al. (1991) Genes Dev., 5, 60-73]. In addition, the lethal overexpression of pck2+ can be suppressed by staurosporine, indicating that fission yeast pck1 and pck2 are molecular targets of this inhibitor. PMID- 8491191 TI - H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. AB - We show that AP-1 is an antioxidant-responsive transcription factor. DNA binding and transactivation by AP-1 were induced in HeLa cells upon treatment with the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC), and upon transient expression of the antioxidative enzyme thioredoxin. While PDTC and NAC enhanced DNA binding and transactivation of AP-1 in response to phorbol ester, the oxidant H2O2 suppressed phorbol ester activation of the factor. H2O2 on its own was only a weak inducer of AP-1. Activation of AP-1 by PDTC was dependent on protein synthesis and involved transcriptional induction of c-jun and c-fos genes. Transcriptional activation of c-fos by PDTC was conferred by the serum response element, suggesting that serum response factor and associated proteins function as primary antioxidant-responsive transcription factors. In the same cell line, the oxidative stress-responsive transcription factor NF-kappa B behaved in a manner strikingly opposite to AP-1. DNA binding and transactivation by NF-kappa B were strongly activated by H2O2, while the antioxidants alone were ineffective. H2O2 potentiated the activation of NF-kappa B by phorbol ester, while PDTC and NAC suppressed PMA activation of the factor. PDTC did not influence protein kinase C (PKC) activity and PKC activation by PMA, indicating that the antioxidant acted downstream of and independently from PKC. PMID- 8491192 TI - The truncation that generated the v-cbl oncogene reveals an ability for nuclear transport, DNA binding and acute transformation. AB - The v-cbl oncogene is the transforming gene of the murine Cas NS-1 retrovirus which induces pre-B cell lymphomas and myeloid leukaemias. Sequencing of c-cbl has revealed that v-cbl was generated by a large truncation that removed 60% of the C-terminus of the corresponding protein. In this study we prepared antibodies to cbl and found that c-cbl encodes a 120 kDa protein which is localized in the cytoplasm with a cytosolic and cytoskeletal distribution. Immunofluorescence studies show a striking pattern of brightly staining vesicles in mitotic cells similar to that observed with cytokeratin antibodies. In contrast to p120c-cbl, which is exclusively cytoplasmic, the p100gag-v-cbl encoded by Cas NS-1 is localized in both the cytoplasm and the nucleus. This redistribution to the nucleus correlates with the ability of cbl to induce acute transformation. Furthermore the truncated protein encoded by v-cbl can bind DNA, unlike the full length protein. These results suggest that the C-terminus of cbl is involved in the retention of p120c-cbl in the cytoplasm and the inhibition of DNA binding. The findings also suggest that a truncated protein encoded by c-cbl exists in the nucleus of normal cells. PMID- 8491193 TI - Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. AB - The retroviral oncogene v-myb encodes a transcriptional activator which is responsible for the activation of the mim-1 gene in myelomonocytic cells transformed by v-myb. The mim-1 promoter contains several myb consensus binding sites and has previously been shown to be regulated directly by v-myb. Here we report that the mim-1 gene is activated synergistically by v-myb and different C/EBP transcription factors. We have cloned a chicken C/EBP-related gene that is highly expressed in myeloid cells and identified it as the chicken homolog of C/EBP beta. A dominant-negative variant of chicken C/EBP beta interferes with the v-myb induced activation of the mim-1 gene in these cells, suggesting that C/EBP beta or another C/EBP transcription factor is required for the activation of mim 1 by v-myb. We found that C/EBP beta and other C/EBP transcription factors confer to fibroblasts the ability to induce the mim-1 gene in the presence of v-myb. Finally we show that, in contrast to v-myb, c-myb synergizes with C/EBP transcription factors only at low concentrations of c-myb protein. Our results suggest a role for C/EBP beta, and possibly for other C/EBP transcription factors, in v-myb function and in myeloid-specific gene activation. PMID- 8491194 TI - The Aspergillus nidulans yA gene is regulated by abaA. AB - The developmentally regulated Aspergillus nidulans yA gene encodes a p-diphenol oxidase that is needed for synthesis of green conidial pigment. We subjected the yA 5' flanking region to mutational analysis in A. nidulans and Saccharomyces cerevisiae to identify DNA sequence elements involved in its transcriptional control, and identified two functionally distinct elements. Element I contained potential BrlA binding sites and was required for full level yA transcription, but not for developmental regulation in the presence of element II. Element II contained putative TEF-1 binding sites flanking a CCAAT element and was sufficient for developmental regulation of transcription. Mutation of the TEF-1 binding sites eliminated developmental regulation, whereas mutation of the CCAAT element led to elevated levels of transcription. Element II was also sufficient to induce transcription in S. cerevisiae when the A.nidulans developmental regulatory gene abaA was expressed from the GAL1 promoter. As AbaA and TEF-1 possess similar DNA binding domains, the abaA-yA interaction in yeast is probably direct. Thus, abaA appears to be a direct activator of yA, but yA regulation may also involve interactions with BrlA and a member of the CCAAT class of DNA binding proteins. PMID- 8491195 TI - asense, a member of the Drosophila achaete-scute complex, is a proneural and neural differentiation gene. AB - The asense (ase) gene of the achaete-scute complex (AS-C) is expressed in the precursors of all adult sensory organs (SOs), the sensory mother cells (SMCs) and in their immediate progeny. Its deletion causes the loss of some SOs and the abnormal differentiation of part of the remaining ones. These defects, which include malformations of the external part of the SOs, duplication of the innervating neuron etc, are enhanced by the haploid condition for the other AS-C genes and are corrected by an ase transgene. We conclude that ase participates, in combination with other members of the AS-C, in implementing the neural program of differentiation of the SMCs. ase also has a proneural function that participates in the singling out of the SMCs that give rise to the recurved bristles of the anterior wing margin. The proneural potential of ase is shown, in addition, by the generation of SOs induced by the generalized expression of an ase gene driven by a hsp70 promoter. PMID- 8491196 TI - Stepwise assembly of hyperaggregated forms of Drosophila zeste mutant protein suppresses white gene expression in vivo. AB - The zeste gene is involved in two chromosome pairing-dependent phenomena: transvection and the suppression of white gene expression. Both require the ability of zeste protein to multimerize, dependent on three interlaced hydrophobic heptad repeats in the C-terminal domain. The first step is dimerization through a leucine zipper. Two other heptad repeats are then required to form higher multimers. The zeta(1) mutation, which causes the pairing dependent suppression of white, creates a new hydrophobic nucleus that allows the formation of a new and larger aggregate. The zeta(op6) mutation, which suppresses even unpaired copies of white, makes even larger aggregates. The phenotypic suppression of white by a series of mutants is strictly correlated with hyperaggregation and the larger the hyperaggregates, the weaker the requirement for the pairing of white. Hyperaggregation of the Z1 protein in vitro is suppressed by co-translation with the C-terminal peptide of wild-type protein, lacking the DNA-binding domain. This C-Z+ peptide also complements the zeta(1) allele in vivo and restores normal color, demonstrating that zeste product also exists in a multimeric complex in the cell. Complementation in vivo is strictly correlated with the prevention of hyperaggregation of the zeste mutant products in vitro, supporting the interpretation that excessive association of zeta(1) and zeta(op6) proteins is responsible for their repression of white gene expression. PMID- 8491197 TI - Multimerization of the Drosophila zeste protein is required for efficient DNA binding. AB - The Drosophila zeste protein forms multimeric species in vitro through its C terminal domain. Multimerization is required for efficient binding to DNA containing multiple recognition sequences and increasing the number of binding sites stimulates binding in a cooperative manner. Mutants that can only form dimers still bind to a dimeric site, but with lower affinity. Mutations or progressive deletions from the C-terminal show that when even dimer formation is prevented, DNA-binding activity is lost. Surprisingly, binding activity is regained with larger deletions that leave only the DNA-binding domain. Additional protein sequences apparently inhibit DNA binding unless they permit multimerization. The DNA-binding domain peptides bind strongly even to isolated recognition sequences and they bind as monomers. The ability of various zeste peptides to stimulate white gene expression in vivo shows that multimeric forms are the functional species of the zeste product in vivo. The DNA-binding domain peptide binds well to DNA in vitro, but it cannot stimulate white gene expression in vivo. This failure may reflect the need for an activation domain or it may be caused by indiscriminate binding of this peptide to non-functional isolated sites. Multimerization increases binding specificity, selecting only sites with multiple recognition sequences. PMID- 8491198 TI - Integration of murine leukemia virus DNA depends on mitosis. AB - In synchronized rat or mouse cells infected with Moloney murine leukemia virus (MLV), integration of viral DNA and production of viral proteins occur only after the cells traverse mitosis. Integration is blocked when cells are prevented from progressing through mitosis. Viral nucleoprotein complexes isolated from arrested cells contain full-length viral DNA and can integrate this viral DNA in vitro, showing that the block to integration in arrested cells is not due to a lack of mature integration machinery. When infected cells traverse mitosis, there is a sharp increase in nuclear accumulation of viral DNA. The dependence of integration on mitosis may therefore be due to a requirement for mitosis and nuclear envelope breakdown for entry of the viral integration complex into the nucleus. PMID- 8491199 TI - Overproduction of the poly(ADP-ribose) polymerase DNA-binding domain blocks alkylation-induced DNA repair synthesis in mammalian cells. AB - The zinc-finger DNA-binding domain (DBD) of poly (ADP-ribose) polymerase (PARP, EC 2.4.2.30) specifically recognizes DNA strand breaks induced by various DNA damaging agents in eukaryotes. This, in turn, triggers the synthesis of polymers of ADP-ribose linked to nuclear proteins during DNA repair. The 46 kDa DBD of human PARP, and several derivatives thereof mutated in its first or second zinc finger, were overproduced in Escherichia coli, in CV-1 monkey cells or in human fibroblasts to study their DNA-binding properties, the trans-dominant inhibition of resident PARP activity, and the consequences on DNA repair, respectively. A positive correlation was found between the in vitro DNA-binding capacity of the recombinant DBD polypeptides and their inhibitory effect on PARP activity stimulated by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Furthermore, overproduced wild-type DBD blocked unscheduled DNA synthesis induced in living cells by MNNG treatment, but not that induced by UV irradiation. These results define a critical role for the second zinc-finger of PARP for DNA single stranded break binding and furthermore underscore the importance for PARP to act as a critical regulatory component in the repair of DNA damage induced by alkylating agents. PMID- 8491200 TI - Tat-dependent occlusion of the HIV poly(A) site. AB - Retroviruses must ensure that poly(A) signals in the 3' LTR are highly active, while identical signals in the 5' LTR are inactive (occluded). In the case of HIV 1, both promoter proximity in the 5' LTR and U3 sequences in the 3' LTR may contribute to this regulation. We have discovered a novel regulatory mechanism for poly(A) site occlusion in HIV-1. When transcription initiation from the HIV promoter is activated by Tat, the HIV poly(A) site is specifically occluded, while other poly(A) sites are unaffected by Tat. Nucleotide signals associated with this Tat effect are immediately adjacent to the AAUAAA sequence of the HIV-1 poly(A) signal. These data suggest that elongating RNA polymerase II, activated by Tat specifically occludes the HIV poly(A) site. PMID- 8491201 TI - Multiple pathways of reversion in viroids for conservation of structural elements. AB - From site-directed mutagenesis of potato spindle tuber viroid (PSTVd) it had been concluded earlier that the formation of a thermodynamically metastable structure containing hairpin II (HP II) is critical for infectivity. In order to differentiate between structural and sequence effects, in the present work base pairs in HP II were exchanged by site-directed double mutations without significant alterations in the native rod-like structure of PSTVd. The mutants were viable and genetically stable in the first generation, but one of the two mutations reverted to the wild-type nucleotide in the second generation. Single site mutations in the stem of HP II, which had been described as revertants to the wild-type sequence earlier, were analysed with respect to the time course of reversion and the sequence variation during reversion. All replicating sequence variants were separated by gel electrophoretic techniques and the sequences and their relative frequencies were determined. From both types of studies it can be concluded (i) that HP II is a functional element in the (-)strand replication intermediate, generated due to sequential folding during synthesis, and that it is essential for template activity of (+)strand synthesis; (ii) that G:U pairs are tolerated transiently in (-)strand HP II; the lower stability of such a HP II is compensated by additional mutations outside HP II which suppress the competition of a rod-like structure; and (iii) that the reversions are generated spontaneously during (-)strand synthesis. Furthermore, the double-stranded structure of HP II is the essential element for short term replication of PSTVd but the exact sequence of the wild-type proves to be superior with regard to fitness and replicability of PSTVd. PMID- 8491202 TI - The td intron endonuclease I-TevI makes extensive sequence-tolerant contacts across the minor groove of its DNA target. AB - I-TevI, a double-strand DNA endonuclease encoded by the mobile td intron of phage T4, has specificity for the intronless td allele. Genetic and physical studies indicate that the enzyme makes extensive contacts with its DNA substrate over at least three helical turns and around the circumference of the helix. Remarkably, no single nucleotide within a 48 bp region encompassing this interaction domain is essential for cleavage. Although two subdomains (DI and DII) contain preferred sequences, a third domain (DIII), a primary region of contact with the enzyme, displays much lower sequence preference. While DII and DIII suffice for recognition and binding of I-TevI, all three domains are important for formation of a cleavage-competent complex. Mutational, footprinting and interference studies indicate predominant interactions of I-TevI across the minor groove and phosphate backbone of the DNA. Contacts appear not to be at the single nucleotide level; rather, redundant interactions and/or structural recognition are implied. These unusual properties provide a basis for understanding how I-TevI recognizes T-even phage DNA, which is heavily modified in the major groove. These recognition characteristics may increase the range of natural substrates available to the endonuclease, thereby extending the invasive potential of the mobile intron. PMID- 8491203 TI - Membrane glycoprotein folding, oligomerization and intracellular transport: effects of dithiothreitol in living cells. AB - Using influenza hemagglutinin (HA0) and vesicular stomatitis virus G protein as model proteins, we have analyzed the effects of dithiothreitol (DTT) on conformational maturation and transport of glycoproteins in the secretory pathway of living cells. While DTT caused reduction of folding intermediates and misfolded proteins in the endoplasmic reticulum (ER), it did not affect molecules that had already acquired a mature trimeric conformation, whether present in the ER or elsewhere. The conversion to DTT resistance was therefore a pre-Golgi event. Reduction of folding intermediates was dependent on the intactness of the ER and on metabolic energy, suggesting cooperativity between DTT and ER folding factors. DTT did not inhibit most cellular functions, including ATP synthesis and protein transport within the secretory pathway. The results established DTT as an effective tool for analyzing the folding and compartmental distribution of proteins with disulfide bonds. PMID- 8491204 TI - Reduction of the disulfide bond of chromogranin B (secretogranin I) in the trans Golgi network causes its missorting to the constitutive secretory pathways. AB - The role of the single, highly conserved disulfide bond in chromogranin B (secretogranin I) on the sorting of this regulated secretory protein to secretory granules was investigated in the neuroendocrine cell line PC12. Treatment of PC12 cells with dithiothreitol (DTT), a membrane permeable thiol reducing agent known to prevent disulfide bond formation in intact cells, resulted in the secretion of newly synthesized chromogranin B, but only slightly decreased the intracellular storage of newly synthesized secretogranin II, a regulated secretory protein devoid of cysteines. The secretion of newly synthesized chromogranin B in the presence of DTT occurred with similar kinetics to those of a heparan sulfate proteoglycan, a known marker of the constitutive secretory pathway in PC12 cells. Analysis of the various secretory vesicles derived from the trans-Golgi network (TGN) indicated that DTT treatment diverted newly synthesized chromogranin B to constitutive secretory vesicles, whereas the packaging of secretogranin II into immature secretory granules was unaffected by the reducing agent. The chromogranin B molecules diverted to constitutive secretory vesicles, in contrast to those stored in secretory granules, were found to contain free sulfhydryl residues. The effect of DTT on chromogranin B occurred in the TGN rather than in the endoplasmic reticulum. We conclude that the sorting of CgB in the TGN to secretory granules is dependent upon the integrity of its single disulfide bond. PMID- 8491206 TI - The cytoplasmic tail of lysosomal acid phosphatase contains overlapping but distinct signals for basolateral sorting and rapid internalization in polarized MDCK cells. AB - Lysosomal acid phosphatase (LAP) is synthesized as a type I membrane glycoprotein and targeted to lysosomes via the plasma membrane. Its cytoplasmic tail harbours a tyrosine-containing signal for rapid internalization. Expression in Madine Darby canine kidney cells results in direct sorting to the basolateral cell surface, rapid endocytosis and delivery to lysosomes. In contrast, a deletion mutant lacking the cytoplasmic tail is delivered to the apical plasma membrane where it accumulates before it is slowly internalized. A chimeric protein, in which the cytoplasmic tail of LAP is fused to the extracytoplasmic and transmembrane domain of the apically sorted haemagglutinin, is sorted to the basolateral plasma membrane. A series of truncation and substitution mutants in the cytoplasmic tail was constructed and comparison of their polarized sorting and internalization revealed that the determinants for basolateral sorting and rapid internalization reside in the same segment of the cytoplasmic tail. The cytoplasmic factors decoding these signals, however, tolerate distinct mutations indicating that different receptors are involved in sorting at the trans-Golgi network and at the plasma membrane. PMID- 8491205 TI - Adaptor self-aggregation, adaptor-receptor recognition and binding of alpha adaptin subunits to the plasma membrane contribute to recruitment of adaptor (AP2) components of clathrin-coated pits. AB - Initiation of receptor-mediated endocytosis by nucleation of clathrin-coated pits involves binding of AP2 adaptor molecules to the plasma membrane. This process was reconstituted in vitro, using plasma membrane fragments, prepared by freeze thaw lysis of cells, and stripped of their endogenous coat proteins, as targets for binding of purified adaptor molecules and their dissociated subunits. The dissociated alpha-adaptin subunit of AP2 bound to plasma membrane fragments, while the dissociated beta-adaptin subunit did not, suggesting that plasma membrane localization of AP2 adaptors is mediated by alpha-adaptin. Membrane binding of intact AP2 adaptor molecules was enhanced by adaptor self-aggregation, which can be modulated by physiological concentrations of inositol phosphates, and may therefore be sensitive to receptor signaling. Adaptor binding was partially inhibited by soluble peptides representing the cytoplasmic domains of the asialoglycoprotein receptor and the polymeric immunoglobulin receptor. These results indicate that direct binding of adaptors to the cytoplasmic domains of receptors contributes to coated pit nucleation but this appears to be a weak interaction, suggesting that an additional recognition signal could be required for high affinity adaptor binding. PMID- 8491207 TI - Synthesis and subcellular location of peroxisomal membrane proteins in a peroxisome-deficient mutant of the yeast Hansenula polymorpha. AB - We have studied the synthesis and subcellular location of peroxisomal membrane proteins (PMPs) in cells of a peroxisome-deficient (per) mutant of the methylotrophic yeast Hansenula polymorpha. Western blot analysis of methanol induced cells of the per mutant, which had been growing in a continuous culture on a glucose/methanol mixture, indicated that various PMPs were normally synthesized. As in wild type (WT) cells, the levels of PMP synthesis appeared to be dependent on specific cultivation conditions, e.g. the carbon source used for growth. In contrast to WT controls, PMPs in methanol-induced per mutants were not subject to proteolytic degradation. Biochemical and immuno(cyto)chemical studies suggested that the PMPs in methanol-induced per cells were located in small proteinaceous aggregates, separated from peroxisomal matrix proteins that were also present in the cytosol. Vesicular membranous structures, resembling the morphology of intact peroxisomes, were never detected irrespective of the growth conditions employed. PMID- 8491208 TI - Functional independence of the protein translocation machineries in mitochondrial outer and inner membranes: passage of preproteins through the intermembrane space. AB - The protein translocation machineries of the outer and inner mitochondrial membranes usually act in concert during translocation of matrix and inner membrane proteins. We considered whether the two machineries can function independently of each other in a sequential reaction. Fusion proteins (pF-CCHL) were constructed which contained dual targeting information, one for the intermembrane space present in cytochrome c heme lyase (CCHL) and the other for the matrix space contained in the signal sequence of the precursor of F1-ATPase beta-subunit (pF1 beta). In the absence of a membrane potential, delta psi, the fusion proteins moved into the intermembrane space using the CCHL pathway. In contrast, in the presence of delta psi they followed the pF1 beta pathway and eventually were translocated into the matrix. The fusion protein pF51-CCHL containing 51 amino acids of pF1 beta, once transported into the intermembrane space in the absence of a membrane potential, could be further chased into the matrix upon re-establishing delta psi. The sequential and independent movement of the fusion protein across the two membranes demonstrates that the translocation machineries act as distinct entities. Our results support a model in which the two translocation machineries can function independently of each other, but generally interact in a dynamic fashion to achieve simultaneous translocation across both membranes. In addition, the results provide information about the targeting sequences within CCHL. The protein does not contain a signal for retention in the intermembrane space; rather, it lacks matrix targeting information, and therefore is unable to undergo delta psi-dependent interaction with the protein translocation apparatus in the inner membrane. PMID- 8491209 TI - TGN38 is maintained in the trans-Golgi network by a tyrosine-containing motif in the cytoplasmic domain. AB - Sorting of proteins destined for different plasma membrane domains, lysosomes and secretory pathways takes place in the trans-Golgi network (TGN). TGN38 is an integral membrane protein found in this intracellular compartment. We show that TGN38 contains an autonomous targeting signal within its cytoplasmic domain which determines its intracellular location. Deletion analysis and site-directed mutagenesis of this domain demonstrate that a tyrosine motif homologous to the internalization signal of surface receptors is necessary and sufficient for correct localization. These findings suggest that TGN38 is maintained in the TGN by retrieval from the plasma membrane and employs a different mechanism for retention from that of the transferase enzymes of the trans-Golgi. PMID- 8491210 TI - Genetic toxicity of fluoride. AB - F- is not mutagenic in standard bacterial systems, but produces chromosome aberrations and gene mutations in cultured mammalian cells. Although there is disagreement in the literature concerning the ability of F- to induce chromosome aberrations in cultured human and rodent cells, the weight of the evidence leads to the conclusion that F- exposure results in increased chromosome aberrations in these test systems. NaF induced primarily chromatid gaps and chromatid breaks, indicating that the rodent cells are responsive in the G2 stage of the cell cycle. In contrast, studies with synchronized human cells indicated that the S phase was the most sensitive. If F- does have a cell cycle-specific effect, it could be expected that differences in the cell treatment and harvest protocols could lead to conflicting results for the induction of chromosome aberrations. Gene mutations were produced in cultured rodent and human cells in the majority of the studies. Unfortunately, a number of the in vitro and in vivo cytogenetic studies are of questionable utility because of the protocols used, the quality of the responses reported, or the interpretations of the data. The conflicting results in the in vivo cytogenetic studies are difficult to reconcile. There are reports of increased chromosome aberrations in rat bone marrow and testes, but other studies, using similar protocols and dose ranges, have reported no induced chromosome damage. Although some of the studies were performed at toxic levels of F-, other studies, including those that showed positive results, were at F- concentrations (1-5 ppm) equivalent to human exposure levels. In the majority of studies that were reported to be positive, there were high background frequencies, or the investigators reported categories of nuclear or chromosome damage that are difficult to interpret. Interestingly, many of the positive results were obtained when anaphase cells were scored, whereas similar treatment protocols in other laboratories yielded negative results when metaphase cells were the only cell type examined. It is difficult, without additional data, to determine the reasons for finding chromosome breaks in anaphase, but not metaphase, cells. Other reports have presented insufficient information to allow adequate evaluations. Therefore, at this time, the question of whether F- produces chromosome damage in vivo should be considered unresolved. PMID- 8491211 TI - Genetic method for pre-classification of genotoxins into monofunctional or cross linking agents. AB - To characterize environmental carcinogens, there is a need to distinguish monofunctional genotoxic agents from those having cross-linking potential, because chemicals which can cross-link DNA are among the most potent carcinogens in rodents [Barbin and Bartsch, 1989] and humans [Allen et al., 1988; Kaldor et al., 1988]. Here we provide a genetic method for a pre-classification of genotoxins with respect to their functionality--monofunctional versus cross linking. The procedure is based on the determination of relative clastogenic efficiency by a two-endpoint comparison in Drosophila: (i) induction of chromosome loss (CL), (ii) incidence of recessive lethal mutations (RL). Analysis of CL/RL ratios of 53 genotoxins, all mutagens in Drosophila, permitted distinction of 45 into two major categories: (i) 21 monofunctional agents with CL/RL indices generally < or = 1; (ii) 24 agents with ratios > 2 exhibiting DNA cross-linking properties. Within the group of monofunctional agents, CL/RL ratios tend to be low for SN1 agents, i.e., for N-ethyl-N-nitrosourea, N-ethyl-N'-nitro N-nitrosoguanidine, and for N-nitrosodiethylamine. With cross-linking agents, the number of reactive groups appeared of minor importance as bi-, tri-, and tetrafunctional agents showed no significant differences in their CL/RL indices. Among 8 chemicals which could not be grouped into one of the two categories are two (adriamycin, daunomycin) regarded as intercalating agents. It is concluded that this two-endpoint analysis in Drosophila has prognostic value and can assist in the characterization of genotoxic agents with unknown mode of action. PMID- 8491212 TI - In vitro system for detecting non-genotoxic carcinogens. AB - Chemical risk assessment has been limited by the inability of in vitro short-term assays to identify the true carcinogenic potential of many substances. Numerous methods exist for identifying mutagenic and clastogenic agents, but a practical means of identifying non-genotoxic carcinogens has remained elusive. Experiments described here suggest that some chemicals may participate in carcinogenesis by modulating the enzymatic processes of drug metabolism. The tumor promoters butylated hydroxyanisole, butylated hydroxytoluene, deoxycholic acid, reserpine, trypan blue, and 12,-O-tetradecanoyl phorbol-13-acetate were chosen as model non genotoxic carcinogens. The enzyme-modulating action of these chemicals was measured using a modified Ames plate incorporation assay whereby the known tumor promoters were plated with a promutagen in the presence of a mammalian metabolic activation system (S9). Each of the non-genotoxic carcinogens significantly increased the mutagenic response of metabolically activated promutagen(s). These experiments suggest that the carcinogenic role of some chemicals may be attributed to their ability to modify the biochemical pathways of drug metabolism. By enhancing or inhibiting the activity of various enzymes, some tumor promoters may create an environment that increases a cell's mutational burden, thereby contributing to neoplastic transformation. PMID- 8491213 TI - Benzene metabolite, 1,2,4-benzenetriol, induces micronuclei and oxidative DNA damage in human lymphocytes and HL60 cells. AB - The triphenolic metabolite of benzene, 1,2,4-benzenetriol (BT), is readily oxidized to its corresponding quinone via a semiquinone radical. During this process, active oxygen species are formed that may damage DNA and other cellular macromolecules. The ability of BT to induce micronuclei (MN) and oxidative DNA damage has been investigated in both human lymphocytes and HL60 cells. An antikinetochore antibody based micronucleus assay was used to distinguish MN containing kinetochores and potentially entire chromosomes (kinetochore-positive, K+) from those containing acentric chromosome fragments (kinetochore-negative, K ). BT increased the frequency of MN formation twofold in lymphocytes and eightfold in HL60 cells with the MN being 62% and 82% K+, respectively. A linear dose-related increase in total MN, mainly in K(+)-MN, was observed in both HL60 cells and lymphocytes. Addition of copper ions (Cu2+) potentiated the effect of BT on MN induction threefold in HL60 cells and altered the pattern of MN formation from predominantly K+ to K-. BT also increased the level of 8-hydroxy 2'-deoxyguanosine (8-OH-dG), a marker of active oxygen-induced DNA damage. Cu2+ again enhanced this effect. Thus, BT has the potential to cause both numerical and structural chromosomal changes in human cells. Further, it may cause point mutations indirectly by generating oxygen radicals. BT may therefore play an important role in benzene-induced leukemia. PMID- 8491214 TI - Genotoxicity analysis of N,N-dimethylaniline and N,N-dimethyl-p-toluidine. AB - N,N-Dimethylaniline (DMA, CAS No. 121-69-7) and N,N-dimethyl-p-toluidine (DMPT, CAS No. 99-97-8) belong to the N-dialkylaminoaromatics, a chemical class structurally alerting to DNA reactivity. Their applications may be industrial (dye and pesticide intermediates, polymerizing agents) and surgical (polymerization accelerators for the manufacture of bone cements and prosthetic devices), thus implying heterogeneous types of human exposure. Findings of carcinogenicity in rodents and some nonexhaustive genotoxicity data are available for DMA, but to our knowledge no information is available on DMPT concerning either carcinogenicity or any kind of genetic toxicity. To investigate their mechanism of action and mutagenic/carcinogenic potential, DMA and DMPT were analyzed for complementary genotoxicity endpoints, namely, gene mutation in Salmonella (Ames test), structural and numerical chromosome aberrations in hamster V79 cells (micronucleus test, matched with an immunofluorescent staining for kinetochore proteins), and in vivo DNA damage in mouse and rat liver (alkaline DNA elution test). The results essentially indicate that both chemicals are chromosome damaging agents. Indeed, at the maximum nontoxic doses, they proved nonmutagenic in Salmonella (although their toxicity did not allow concentrations > 70 micrograms/plate to be tested) and weakly positive in inducing DNA damage (increases in DNA elution rates at most approximately 2.4 times control value). Conversely, they proved clearly positive in inducing numerical chromosome alterations, with dose-dependent increases up to more than five times the control value for DMPT. At the highest dose tested, both chemicals also showed a significant clastogenic effect. PMID- 8491215 TI - Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O-acetyltransferase and nitroreductase activities. AB - A highly sensitive umu test system for the detection of genotoxic activities of a variety of mutagenic nitroarenes has been developed using a new tester strain, Salmonella typhimurium NM3009 having high O-acetyltransferase (O-AT) and nitroreductase (NR) activities. The NM3009 was constructed by subcloning both the O-AT and NR genes into plasmid vector pACYC184, and the resulting plasmid was introduced into the parent tester strain S. typhimurium TA1535/pSK1002 harboring an umuC'-'lacZ fusion gene. The induction of umuC gene expression could be monitored by measuring the cellular beta-galactosidase activity produced by fusion gene. The purpose of the study was to evaluate whether the newly developed strain NM3009 is highly sensitive toward nitroarene compounds. The sensitivity of the strain NM3009 was compared with those of the parent TA1535/pSK1002 strain, the NR-overexpressing strain NM1011, the NR-deficient strain NM1000, the O-AT overexpression strain NM2009, and the O-AT-defective strain NM2000. The newly developed NM3009 strain had about 13-fold and 3-fold higher activities for N-AT and NR, respectively, than the original S. typhimurium TA1535/pSK1002 strain. Among six strains tested, NM3009 showed the highest sensitivity toward such chemicals as 1-nitronaphthalene, 2-nitrofluorene, 3,7-dinitrofluoranthene, 3 nitrofluoranthene, 5-nitroacenaphthene, 2-nitronaphthalene, 1-nitropyrene, 1,6 dinitropyrene, 3,9-dinitrofluoranthene, 4,4'-dinitrobiphenyl, 1,8-dinitropyrene, m-dinitrobenzene, 2,4-dinitrotoluene, and 1,3-dinitropyrene. We have also found that the order of sensitivities to induce umuC gene expression toward a variety of nitroarenes was NM3009 > NM2009 > NM1011 > TA1535/pSK1002 > NM2000 > NM1000. These results suggest that the newly developed tester strain NM3009 is of great use for the detection of genotoxic activities of numerous carcinogenic and mutagenic chemicals including nitroarenes, which require NR and/or O-AT for the activation. PMID- 8491216 TI - Mutagenicity of soluble and insoluble nickel compounds at the gpt locus in G12 Chinese hamster cells. AB - Nickel is an established human and animal carcinogen, but efforts to demonstrate its mutagenicity in a number of cell types have not been successful. In this report we describe the mutational response to nickel compounds in the G12 cell line, an hprt deficient V79 cell line containing a single copy of the E. coli gpt gene. This cell line has a low spontaneous background, making it suitable for assessment of mutagenic responses to environmental contaminants. When G12 cells were treated with insoluble particles of crystalline nickel sulfide < 5 microns in diameter, a strong, dose-dependent mutagenic response was observed up to 80 times the spontaneous background. Of 48 mutant gpt(-) clones isolated that were induced by insoluble nickel, all were capable of DNA amplification of the gpt sequences by polymerase chain reaction (PCR). The ability to produce full-length PCR products is an indication that large deletions of gene sequences have not occurred. When G12 cells were treated with soluble nickel sulfate, the mutational response was not significantly increased over the spontaneous background. This difference in mutagenic response reflects a large difference in the mutagenic potential of soluble and insoluble nickel compounds, which reflects the carcinogenic potential of these forms of nickel. PMID- 8491217 TI - In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs. AB - The aim of this study was to develop an in vitro human peripheral lymphocyte micronucleus bioassay involving phytohemagglutinin stimulant for urines containing adriamycin (ADR) and cyclophosphamide (CP). In vitro studies with defined concentrations of ADR, CP, and fresh urine showed that mitotic indices and micronuclei counts/1,000 cells had to be log (X + 1) transformed to be able to use parametric statistics and that a specific micronucleus assay for ADR in the presence of CP and urine for 5-15 ng ADR/mL had been developed. Whereas CP alone could be detected between 196-522 micrograms/mL, this effect was abolished in the presence of 15 ng ADR/mL. Interdonor variabilities relative to ADR sensitivity and CP linear dynamic range were marked, but intradonor variability was small. The MN bioassay tolerated < 10% urine. Results for urines from nine patients receiving antineoplastic drugs (CP, all; ADR, 3; 5-fluorouracil, 3; methotrexate, 3; vincristine, 4; procarbazine, 1; and megestrol acetate, 1) showed that only 1/3 patients given ADR were detected, and two others not given ADR were positive. All frozen urines from the 12 control subjects and the nine patients exhibited depressed mitotic index, with, however, no control patient urines inducing increased micronuclei. Two patients had urines of undefined genotoxic potential since undepressed mitotic indices were not attainable by dilution. The effects of combination chemotherapy in addition to freezing and storage influences were complex. More research is required to be able to interpret the results. PMID- 8491218 TI - Modification of clastogenicity of three known clastogens by garlic extract in mice in vivo. AB - The anticlastogenic activity of crude extract of garlic (Allium sativum L.) was studied in bone marrow cells of mice. Male laboratory-bred Swiss albino mice were given one of three concentrations of the freshly prepared extract (100 mg, 50 mg, and 25 mg/kg body weight) as a dietary supplement by gavage for 6 consecutive days. On the seventh day the mice were administered a single acute dose of two known clastogens, mitomycin C(1.5 mg/kg) and cyclophosphamide (25 mg/kg) or sodium arsenite (2.5 mg/kg), simultaneously with garlic extract. After 24 hr, chromosome preparations were made from the bone marrow cells. The endpoint studied were chromosomal aberrations and damaged cells. Garlic extract alone induced a low level of chromosomal damage. The clastogenicity of all three mutagens were reduced significantly in the animals which had been given garlic extract as dietary supplement. The extent of reduction was different for the three clastogens and may be attributed to the interaction with the different components of the extract. PMID- 8491219 TI - Dual-photon and dual-energy X-ray absorptiometry for the measurement of total body bone mineral and soft tissue composition. PMID- 8491220 TI - Somatostatin analogue scintigraphy in carcinoid tumours. AB - Scintigraphy with iodine-123 or indium-111 labelled somatostatin analogue (octreotide) was performed in 52 patients diagnosed as, suspected of, or at risk of having carcinoid tumours. In 32 of 37 (86%) patients in whom histologically proven carcinoids were still present, known tumour sites were visualized. Using 123I-coupled octreotide, 24 of 40 (60%) known extrahepatic sites were visualized, whereas all of 12 (100%) extrahepatic lesions were visualized after injection of 111In-coupled octreotide. Known liver metastases were not distinctly visualized with octreotide scintigraphy in 12 of 24 patients. In all but two of these cases, an even distribution of radioactivity in the liver was observed. This is most probably due to the fact that these liver metastases accumulated about as much radioactivity as does normal liver tissue. Previously unsuspected localizations or sites not recognized with other imaging techniques were found in 20 of the 37 patients. In 3 of 11 patients who were thought to have been surgically cured, and in 4 of 4 patients who were suspected of having carcinoids, octreotide scintigraphy showed abnormal accumulation of radioactivity. Histological or radiological evidence that additional sites noticed on octreotide scintigrams indeed represented tumour tissue was obtained in ten patients. Visualization of the carcinoids did not depend on the site of the tumour or on the presence or absence of hormonal hypersecretion, as measured by urinary 5-hydroxyindoleacetic acid and serum alpha-subunit concentrations. Apart from its use for tumour localization, octreotide scintigraphy, in consequence of its ability to demonstrate somatostatin receptor positive tumours, could be used to select those patients with the carcinoid syndrome who are likely to respond favourably to octreotide treatment. PMID- 8491221 TI - Iodine-123 labelling of atrial natriuretic peptide and its analogues: initial results. AB - Receptors for atrial natriuretic peptide (ANP) are known to be present in many organs, e.g. brain, liver and kidney. The aim of this study was to optimize the labelling method for ANP analogues with iodine-123 and to describe their pharmakokinetics. ANP 99-126, atriopeptin III, Tyr-atriopeptin II and urodilatin were labelled by the Iodogen method. Of the various labelling conditions tested, the Iodogen procedure with 10 micrograms Iodogen, 10 micrograms peptides in 100 microliters phosphate buffer (pH 7.2) and a reaction time of 60 min proved to be optimal. Separation was performed using a Sep-pak reversed-phase extraction cartridge. In all cases quality control by thin-layer chromatography resulted in a radiochemical purity higher than 98%. After intravenous administration of 15 MBq/kg kinetic profiles of various organs in rabbits were investigated by whole body scintigraphy with a gamma camera. Organ kinetics showed accumulation and excretion via the kidney. No bowel accumulation was observed. Interestingly, increasing tracer uptake in the head region was registered with three of the four tested tracers. Liver accumulation decreased rapidly during the first 40 min. No tracer degradation was registered over the whole time period, as shown by the low thyroid accumulation with a maximum of only 1%. Thus, labelling of ANF and its analogues is possible. These compounds seem to be of interest for further experiments and perhaps clinical studies because of their potential for brain receptor imaging. PMID- 8491222 TI - Indium-111-labelled cationic complexes of aminothiols: structure-activity correlation. AB - In the present work a series of NxS2 ligands were synthesized, investigated for the formation of cationic, indium chelates and evaluated comparatively in experimental animals. The compounds under study formed indium complexes which were stable in vitro and presented myocardial uptake. Animal studies showed that the chemical structure of the ligand plays an important role in biodistribution. A system of one six-membered and two five-membered rings, formed by the metal and the donor atoms of the ligand, may constitute a basic structure for the development of new indium tracers with myocardial affinity. PMID- 8491223 TI - Factors affecting myocardial 2-[F-18]fluoro-2-deoxy-D-glucose uptake in positron emission tomography studies of normal humans. AB - The goal of this study was to identify the anatomic and physiologic factors affecting left ventricular myocardial 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) uptake and myocardial glucose utilization rates (MRGlc) in normal humans. Eighteen healthy male volunteers were studied in the fasting state (4-19 h) and 16 after oral glucose loading (100 g dextrose) with positron emission tomography (PET) and FDG. Substrate and hormone concentrations were measured in each study. The kinetics of myocardial FDG uptake were evaluated using both a three compartment model and Patlak graphical analysis. Systolic blood pressures and rate pressure products were similar in the fasting and postglucose states. MRGlc averaged 0.24 +/- 0.17 mumol/min/g in fasting subjects and rose to 0.69 +/- 0.11 mumol/min/g after glucose loading. Phosphorylation rate constant, k3, and MRGlc were linearly related (P < 0.001). Increases in MRGlc following glucose loading were correlated with plasma glucose, insulin and free fatty acid concentrations, ratios of insulin to glucagon levels, and influx rate constants of FDG. Glucose loading improved the diagnostic image quality due to more rapid clearance of tracer from blood and higher myocardial FDG uptake. When MRGlc, glucose and insulin concentrations, and insulin to glucagon ratios exceeded 0.2 mumol/min/g, 100 mg/dl, 19 microU/ml, and 0.2 microU/pg, respectively, myocardial uptake of FDG was always adequate for diagnostic use. FDG image quality and MRGlc were similar after relatively short (6 +/- 2 h) and overnight (16 +/- 2 h) fasting. Significant (P < 0.05) regional heterogeneity of myocardial FDG uptake and MRGlc was observed in both the fasting and the postglucose studies. MRGlc and FDG uptake values in the posterolateral wall were higher than those in the anterior wall and septum. Thus, both 6-h and overnight fasts resulted in similarly low myocardial glucose utilization rates. While MRGlc and myocardial FDG uptake depended on plasma glucose, free fatty acid, and insulin concentrations, the results also suggest an additional dependency on plasma glucagon levels. Regional heterogeneities in myocardial FDG uptake and MRGlc are evident and independent of the subjects' dietary state. These regional heterogeneities need to be considered in studies of patients with cardiac disease. PMID- 8491224 TI - A comparison of dobutamine and maximal exercise as stress for thallium scintigraphy. AB - In the assessment and evaluation of patients with suspected coronary artery disease there is a need for pharmacological stress combined with thallium scintigraphy. Thallium images were obtained following stress both with dobutamine infusion (5-20 micrograms kg-1 min-1) and with symptom-limited bicycle ergometry in 20 patients (age 39-70 years) with chest pain who had been admitted for coronary angiography. Percentage thallium uptake was calculated using a region of interest technique. Detailed comparison was performed of the presence, size and distribution of left ventricular thallium perfusion defects; the percentage thallium uptake in ventricles, lung and liver; and the haemodynamic response to stress. Each stress produced a similar number of abnormal segments in each of three views (total EX 166/300; DOB 167/295), but exercise produced larger defects in the anterior view (P < 0.025). Thallium uptake in left and right ventricles and relative uptake to lungs were similar, but dobutamine produced higher relative liver uptake [EX 1.55 (0.67); DOB 2.97 (1.23) P < 0.0001]. Fourteen patients were able to tolerate dobutamine 20 micrograms kg-1 min-1. The ratio of peak stress to rest double product was smaller with dobutamine in both patients with (DOB 1.3; EX 2.0; P < 0.0047) and patients without beta-blockade (DOB 1.5; EX 2.4; P < 0.008). Dobutamine produced fewer conventional stress endpoints of chest pain and ST depression. In conclusion, dobutamine produces a well-tolerated incremental pharmacological stress with thallium images similar to maximal exercise, and provides a useful alternative stress in patients unable to perform adequate dynamic exercise. PMID- 8491225 TI - Apparent change in cardiac geometry during single-photon emission tomography thallium-201 acquisition: a complex phenomenon. AB - We investigated the frequency and extent of changes in heart position and geometry independent of body motion during stress single-photon emission tomography (SPET) thallium-201 myocardial perfusion imaging. Following an exercise treadmill test, patients had a 22.1-min SPET acquisition which was followed immediately by a static image acquisition for 1 min with the camera position identical to the first view of the SPET study. Point sources were placed on the body to monitor patient motion. Cardiac motion was assessed by an approach which mimicked a cross-correlation technique applied to cardiac count profiles along the horizontal and vertical directions from the first view of the SPET study and the static image. A large percentage (87.5%) of cases had some degree of horizontal or vertical motion. Pixel shifts in cardiac position of > or = 2 pixels (12 mm) occurred in 60% of patients. In 37% of patients who moved the cardiac motion was consistent with simple translation of the heart and thus amenable to correction using proposed SPET motion-correction programs. The peak heart rate achieved during stress and the ratio of the heart rate immediately before SPET acquisition to the resting heart rate were determined to be independent predictors of patient motion during SPET acquisition. Cardiac motion changes were minimal at (13.3 +/- 2.2) min after cessation of exercise. The implications of these findings for the accuracy of SPET 201Tl require further investigation. PMID- 8491226 TI - A simple two-strip method to determine the radiochemical purity of technetium-99m mercaptoacetyltriglycine. AB - Technetium-99m mercaptoacetyltriglycine (MAG3) has been used extensively as a renal function agent for several years. Radioimpurities in the MAG3 kit preparation are not only concentrated and excreted in the kidneys. Therefore proper quality control for renal studies is even more important to make possible a rapid and adequate interpretation of diagnostic studies. The standard method to determine the radiochemical purity is high-performance liquid chromatography (HPLC), which is time consuming and expensive. We set up a new simple thin-layer chromatography (TLC) method based on instant thin-layer silica gel strips as stationary phase for checking the main impurities, free pertechnetate and reduced hydrolysed 99mTc-colloid. Comparison of TLC and HPLC results showed no significant differences (t-test, P < 0.05); the correlation between the results obtained with the two methods in respect of the free pertechnetate content was excellent (r = 0.99913). The TLC method was also efficient in determining the percentage of 99mTc-colloid. The main impurity found in 37 routine preparations was free pertechnetate; the mean radiochemical purity was 97.95%. The time required to perform the analysis was less than 20 min. The new TLC system is a cheap, simple, fast, reliable and accurate method for the quality control of the MAG3 kit preparation, and is especially suitable for routine use. PMID- 8491227 TI - Technetium-99m hexamethylpropylene amine oxime single photon emission tomography of the brain in early Parkinson's disease: correlation with dementia and lateralization. AB - Regional cerebral blood flow was assessed in 19 patients with early idiopathic Parkinson's disease (PD) and 12 control subjects of similar age by single-photon emission tomography using technetium-99m hexamethylpropylene amine oxime (HMPAO). Of the patients with PD, seven were mildly demented and 15 presented with hemiparkinsonism. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. Mean cortical and regional uptake ratios in non-demented PD patients were not significantly different from values in the controls. In contrast, besides generalized cortical hypoperfusion, demented PD patients had significantly lower HMPAO uptake in the frontal and basal ganglia regions than non-demented patients. These observations support the hypothesis of impaired neuronal activity in both cortical and subcortical regions of the brain in demented PD patients. In hemiparkinsonian patients, the only asymmetrical finding was a relative hypoperfusion in the contralateral parietal region. This may be due to deafferentation of the thalamoparietal pathways. The lack of asymmetrical uptake in basal ganglia in our PD patients may be explained by their staging at the time of the investigation (stage I and II, Hoehn and Yahr scale). PMID- 8491228 TI - Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass. AB - An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (rho = -0.510), developed using surgical samples was of the form u = amb and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was an iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. PMID- 8491229 TI - Wire chambers revisited. AB - Detectors used for radioisotope imaging have, historically, been based on scintillating crystal/photomultiplier combinations in various forms. From the rectilinear scanner through to modern gamma cameras and positron cameras, the basic technology has remained much the same. Efforts to overcome the limitations of this form of technology have foundered on the inability to reproduce the required sensitivity, spatial resolution and sensitive area at acceptable cost. Multiwire proportional chambers (MWPCs) have long been used as position-sensitive charged particle detectors in nuclear and high-energy physics. MWPCs are large area gas-filled ionisation chambers in which large arrays of fine wires are used to measure the position of ionisation produced in the gas by the passage of charged particles. The important properties of MWPCs are high-spatial-resolution, large-area, high-count-rate performance at low cost. For research applications, detectors several metres square have been built and small-area detectors have a charged particle resolution of 0.4 mm at a count rate of several million per second. Modification is required to MWPCs for nuclear medicine imaging. As gamma rays or X-rays cannot be detected directly, they must be converted into photo- or Compton scatter electrons. Photon-electron conversion requires the use of high atomic number materials in the body of the chamber. Pressurised xenon is the most useful form of "gas only" photon-electron convertor and has been used successfully in a gamma camera for the detection of gamma rays at energies below 100 keV. This camera has been developed specifically for high-count-rate first pass cardiac imaging. This high-pressure xenon gas MWPC is the key to a highly competitive system which can outperform scintillator-based systems. The count rate performance is close to a million counts per second and the intrinsic spatial resolution is better than the best scintillator-based camera. The MWPC camera produces quantitative ejection fraction information of the highest quality. The detection of higher energy gamma rays has proved more problematical, needing a solid photon-electron convertor to be incorporated into the chamber. Several groups have been working on this problem with modest success so far. The only clinical detectors have been developed for positron emission tomography, where thin lead or lead-glass can provide an acceptable convertor for 511 keV photons. Two MWPC positron cameras have been evaluated clinically and one is now in routine use in clinical oncology. The problems of detection efficiency have not been solved by these detectors although reliability and large-area PET imaging have been proven.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8491230 TI - Toward a useful measure of flood-field uniformity: can the beauty in the eye of the beholder be quantified? PMID- 8491231 TI - Comparison of technetium-99m MAG3 kit formulations in Europe and the USA. PMID- 8491232 TI - The small intestine and colon. PMID- 8491233 TI - Study of the efficacy of nicorandil in patients with ischaemic heart disease using Exercise-T1-201 myocardial tomography. AB - The effect of nicorandil on myocardial perfusion in ischaemic heart disease has been studied using exercise-load T1-201 myocardial SPECT (Ex-SPECT). Ex-SPECT was carried out in 12 patients with previous myocardial infarction (OMI) and 9 with angina pectoris (AP) before and after administration of nicorandil 15 mg/day, for three or more weeks; % T1 uptake and the washout rate in infarcted or ischaemic areas were calculated from short axial images using the Bull's eye method. In the OMI group, % T1 uptake and washout rates in the infarction areas improved significantly from 52.4% and 0.25 before nicorandil to 60.4% and 0.38 after it. In the AP group, too, % T1 uptake and washout rates showed a significant improvement from 56.9% and 0.10 before to 69.1% and 0.33 after administration. Six subjects who had not received the drug, and who showed negative washout rates, had high improvement rates when nicorandil was administered, suggesting that the drug could increase myocardial perfusion during exercise loading as well as suppressing coronary spasm. Ex-SPECT was done in 4 subjects before and after nicorandil and after subsequent surgical treatment (PTCA or CABG) and the effects of the two therapies were compared. The washout rate was improved from 0.01 to 0.34 by administration of nicorandil, and a notable increase in coronary artery blood flow was achieved compared to the level after surgical treatment, i.e. 0.50. It was concluded that, normal dosages of nicorandil have a powerful direct effect of dilating the coronary arteries without any influence on preload or afterload. PMID- 8491234 TI - Effect of trospium chloride on gastrointestinal motility in humans. AB - The aim of this double-blind, placebo-controlled, cross-over study was to investigate the effect of trospium chloride on gall bladder contraction, gastric emptying of a liquid meal, gastrooesophageal reflux, and orocaecal transit time in healthy subjects. Gall bladder contraction was examined by ultrasonography before and after stimulation with two raw eggs. Gastric emptying was evaluated by an intubation technique and by sonography. To determine gastrooesophageal reflux and orocaecal transit time, 24-hour pH metry and a hydrogen breath test were used. The gall bladder ejection fractions were significantly lower after oral treatment with both 4 x 10 mg and 4 x 20 mg trospium compared to placebo, but no difference was seen between the two doses of drug. Gastric emptying of a liquid meal was significantly delayed after intake of 4 x 15 mg trospium, whilst the time course of the intragastric volume determined by ultrasound did not differ from that after placebo, suggesting an antisecretory effect of trospium on gastric secretion. The fractional time of oesophageal pH < 4 as a percentage of the entire 24-hour investigation period was significantly increased by treatment with trospium 3 x 15 mg per day. The orocaecal transit time of 10 g lactulose was significantly prolonged. Provided that the observed effects on gall bladder contraction, gastric emptying, and orocaecal transit time are reproduced in disease states, trospium should be regarded as a potentially useful antispasmodic agent. PMID- 8491235 TI - A clinical pharmacological study of subcutaneous nicotine. AB - The stable isotope-labeled compound 3',-3'-dideuteronicotine (nicotine-d2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg). Peak plasma nicotine concentration correlated well with the dose, averaging 2.8 to 14.8 ng/ml, 19 to 25 min after injection of the 0.4 mg and 2.4 mg doses, respectively. The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml.min-1.kg-1, similar to the clearance reported previously for intravenously administered nicotine. Thus, bioavailability appears to be approximately 100%. The heart rate response was more sensitive to the nicotine dose than the blood pressure response. Subjective effects showed large interindividual variability. The results reported herein may be useful in planning future studies. Administration of nicotine by the subcutaneous route appears to be a practical and safe method for studying the human pharmacology of nicotine. PMID- 8491236 TI - Bioavailability of controlled release carbamazepine estimated by mixed effect modelling. AB - The absorption properties of a conventional tablet of carbamazepine (T) and a controlled release form of carbamazepine (TCR) have been compared using a nonlinear mixed effect model (NONMEM). Plasma carbamazepine concentration data were obtained from an open, steady-state, crossover bioavailability study in which 494 measurements were obtained from 13 patients, with an equal number of samples per patient for each dosage form. The pharmacokinetic model used as a one compartment open model with first-order absorption and elimination. The objective function was used as a measure of the goodness of fit of the model to the data. Body weight was an important determinant of carbamazepine clearance (CL) but not volume of distribution (V). Accounting for the interindividual variability in volume of distribution did not significantly influence the objective function. Including different rates of absorption (ka) for the two dosage forms resulted in a significant improvement in the objective function, as well as reducing the interindividual variability in the rate of absorption. Adding a parameter for relative bioavailability (f) of TCR improved the objective function statistically, but an unrealistic value for V was obtained, and the absorption and elimination rates appeared to be transposed in the classical "flip-flop" manner. Fixing V to the value obtained before introducing f did not change the objective function and permitted estimation of f without the confounding influence of excessive parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491237 TI - Dose-dependent uricosuric effect of ambroxol. AB - Ambroxol is known to promote bronchial secretion and is used as an expectorant. Previous studies had suggested that high doses of ambroxol could reduce the plasma uric acid concentration. The present study was undertaken to confirm this finding, to determine its dose-response relationship and to identify the underlying mechanism of action. Using a placebo-controlled, double-blind parallel group design, 48 healthy male volunteers were randomly allocated to receive placebo b.d. and ambroxol 125 mg b.d., 250 mg b.d. or 500 mg b.d. (12 subjects per group). The subjects were hospitalised during a dietary run-in period of 3 days (Days -3 to -1) and a treatment period of 5 days (Days 1 to 5). On Day -1 (baseline) and Days 1 to 5, all urine was collected and blood samples were taken for the analysis of uric acid, creatinine, xanthine and ambroxol. The measurements were repeated four days after treatment had closed. Steady state plasma concentrations of ambroxol (trough levels) were reached after 2 or 3 days and were linearly related to dose. Ambroxol induced a significant, dose dependent, reduction in plasma uric acid (250 mg b.d. about 20%; and at 500 mg b.d. about 30%). The diurnally fluctuating uric acid clearance was dose dependently increased and there was no notable effect on creatinine clearance. Plasma hypoxanthine levels were not affected by ambroxol. No severe adverse events were reported and no drug induced changes in the clinical laboratory values were observed. It is concluded that ambroxol has an uricosuric action following oral administration of higher doses (250 mg-500 mg b.d.) and it is well tolerated. PMID- 8491238 TI - Plasma concentration-effect relationship of metoprolol during and after pregnancy. AB - The plasma drug concentration-effect relationship after an oral dose of 100 mg metoprolol has been studied in 8 women in the third trimester of a pregnancy complicated by hypertension. The study was repeated 3-5 months after parturition when all but 2 women were normotensive. Systolic and diastolic blood pressures (SBP and DBP) were measured in the sitting position followed by the change in heart rate on exercise. The average peak plasma concentration of metoprolol was almost 4-times higher in the non-pregnant state. Despite this difference, the reduction in exercise tachycardia and resting SBP was only slightly more pronounced after delivery than during pregnancy. In relation to the plasma drug concentration, metoprolol had four-times and twice the effect on heart rate and SBP during pregnancy as compared to the post partum period. The altered chronotropic response to metoprolol during pregnancy may be due to increased sensitivity or altered function of the beta-adrenergic system. PMID- 8491239 TI - Single dose pharmacokinetics of proguanil and its metabolites in pregnancy. AB - Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng.ml-1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng.h.ml-1.kg-1, respectively. Corresponding whole blood AUC values were 361 and 396 ng.h.ml-1.kg-1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng.ml-1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml-1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491240 TI - Assessment of bioelectrical impedance for individualizing gentamicin therapy in neonates. AB - The use of bioelectrical impedance (BI) analysis as a non-invasive approach for individualizing gentamicin therapy in newborn infants has been investigated in a two phase study. In Phase I, 1/impedance and length were identified as statistically significant predictors of the distribution volume of gentamicin (Adj R2 = 0.78, CV = 12.42%), and length/impedance and post-conceptual age were predictors of total systemic clearance (Adj R2 = 0.83, CV = 14.5%), following the administration of 2.5 mg.kg-1 gentamicin to 17 neonates (gestational age (GA) 27 to 36 weeks). In a prospective validation of these relationships in an independent (Phase II) group of 27 infants (GA 26 to 41 weeks), predicted serum gentamicin concentrations were close to those achieved. Several instances of high prediction errors (predicted minus achieved levels) were observed in infants with known or suspected renal impairment and they caused significant (P < 0.05) perturbation in the bias and accuracy of the models. Daily BI measures over a four to five day period were able to detect individual changes in the fat-free body compartments, which were translated into alterations in gentamicin regimens. This simple, non-invasive and relatively inexpensive bedside technique provides a potentially valuable means to individualize gentamicin therapy without relying on the measurement of serum gentamicin concentration. PMID- 8491241 TI - Sulphation and glucuronidation of ritodrine in human foetal and adult tissues. AB - Ritodrine is a beta 2-adrenoceptor agonist used for the management of preterm labour. It is inactivated by conjugation with sulphate and glucuronic acid. There is more ritodrine sulphate than ritodrine glucuronide in urine from the newborn whereas equal amounts of ritodrine glucuronide and sulphate are excreted in maternal urine [Clin. Pharmacol. Ther 44, 634-641, 1988]. We show that, in the mid-gestational human fetal liver, ritodrine sulphotransferase is well expressed, whereas the glucuronidation of ritodrine is little developed compared to the adult liver. The average sulphotransferase activity was 308 pmol.min-1 per mg protein in fetal (N = 48) and 145 pmol.min-1 per mg protein in adult (N = 32) liver. The rates of ritodrine sulphation in fetal gut, lung and kidney were higher than in the corresponding adult tissues. The development and tissue distribution patterns of ritodrine sulphotransferase are consistent with those of dopamine sulphotransferase. Ritodrine and dopamine are sulphated by thermolabile enzymes. The activity of glucuronyl transferase was measurable in only 5 of the 48 foetal livers assayed, and in those in which could be assayed, the average activity was 44.6 pmol.min-1 per mg protein, one-tenth of that in adult livers (524 pmol.min-1 per mg protein). PMID- 8491242 TI - On the intraindividual variability and chronobiology of cyclosporine pharmacokinetics in renal transplantation. AB - The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0-12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0 12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0-12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng.ml-1 versus 223 ng.ml-1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation. PMID- 8491243 TI - Chloroquine in malaria. Isn't it time for revision of prophylaxis schedules? AB - Two antimalarial prophylactic regimens were compared in healthy subjects belonging to the flying personnel of Scandinavian Airlines System. Regimen I: 310 mg chloroquine (CQ) base was given once weekly, starting the week prior to departure to the endemic area, then weekly during presence there and for four weeks after return. Regimen II: a loading dose of 620 mg chloroquine base was given at the latest 48 h prior to departure to the endemic area, followed by 310 mg base weekly throughout the visit. Blood samples were analysed by HPLC for CQ and its major metabolite desethylchloroquine (CQM). Regimen I gave suboptimal whole blood concentrations of CQ and CQM at the end of the first week of treatment. Regimen II gave prophylactic concentrations from the beginning of visit up to 6 weeks after departure from the endemic area. Both regimens were well tolerated, but Regimen II appeared better accepted by the volunteers due to its shorter duration. PMID- 8491244 TI - Prevention of postoperative swelling and pain by dexamethasone after operative removal of impacted third molar teeth. AB - In a placebo-controlled double-blind study, we examined the effect of perioperative oral administration of 6 mg dexamethasone, given once 12 h before and once 12 h after osteotomy of two impacted molar teeth, on postoperative edema, limitation of jaw opening, and intensity of postoperative pain. On the first day after surgery the difference in the increase in cheek swelling was 54.3% (P < 0.001) as measured with a tape, 46% (P < 0.001) measured with a gauge in the first molar area and 29% (P < or = 0.056) by sonographic measurement of the cheek diameter in the molar area. The limitation in the jaw opening was reduced by 17.7% (P < 0.002) after dexamethasone. Pain assessed by visual analog scale was reduced by dexamethasone by 50% (P < 0.01). The amount of analgesics required postoperatively (codeine phosphate) was reduced by 37% (P = 0.02) following dexamethasone administration. Seventy-six percent of our patients preferred perioperative medication of dexamethasone. PMID- 8491245 TI - The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin. AB - In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n = 6) or doxazosin 2 mg (Group 2, n = 6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated. BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy. The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml.min-1 during monotherapy with doxazosin. There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng.ml-1.h for the 4 study days (Group 2). PMID- 8491246 TI - The effects of the COMT inhibitor nitecapone for one week on exercise haemodynamics and catecholamine disposition. AB - We have studied resting and exercise haemodynamics and catecholamine disposition after catechol-O-methyl-transferase (COMT) inhibition with nitecapone 100 mg t.d.s. for 7 days in 15 healthy men (aged 21 to 28 y) in a placebo-controlled, cross-over study. Nitecapone did not alter resting or exercise heart rates, blood pressure, or plasma catecholamine concentrations, but it altered the metabolic profile of endogenous catecholamines, as shown by: (1) a fall in the concentrations of the COMT-dependent metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) by 22% (P < 0.01), (2) increases in plasma concentrations of the monoamine oxidase-dependent metabolites 3,4-dihydroxyphenylglycol (DHPG) by up to 90% (P < 0.001) and 3,4-dihydroxyphenylacetic acid (DOPAC) by 67% (P < 0.05), (3) a three fold increase in the concentration of circulating conjugated adrenaline (P < 0.001). PMID- 8491247 TI - In vivo binding characteristics of carbamazepine and carbamazepine-10,11-epoxide to serum proteins in paediatric patients with epilepsy. AB - The in vivo serum protein binding characteristics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) were assessed in sera from 23 paediatric patients on CBZ monotherapy. We assumed that CBZ and CBZ-E binding to serum proteins comprised specific binding sites on alpha 1-acid glycoprotein (AAG) and non-specific binding sites on serum albumin. Therefore, the binding characteristics of each compound were analysed according to specific and nonspecific binding equations. Association constants for drug-AAG binding were 0.096 l.mumol-1 for CBZ and 0.023 l.mumol-1 for CBZ-E. Within the concentration ranges investigated the specific binding of each compound contributes to the drug serum protein interactions. Age did not show a significant correlation with the serum unbound fraction of each compound. PMID- 8491248 TI - Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. AB - The influence of usual multiple ingestions of dietary caffeine on oral single dose pharmacokinetics of theophylline has been investigated in 6 healthy male subjects. The subjects consumed 2 to 7 cups of regular instant coffee during the 24 h study period. Their mean serum concentrations of caffeine varied from 1.2 to 3.1 mg/l. After their usual intake of dietary caffeine, the serum concentrations of theophylline from 3 to 24 h after administration were significantly higher than after deprivation of dietary caffeine. The apparent elimination of theophylline half-life was prolonged from 6.3 (0.61) h (mean with (SEM)) to 8.3 (0.47) h (32% increase, P < 0.01) and the total body clearance was reduced from 55.0 (1.31) ml.h-1.kg-1 to 42.5 (2.63) ml.h-1.kg-1 (23% decrease, P < 0.001). Saturation of theophylline metabolism and/or competition between theophylline and caffeine metabolism in addition to theophylline derived from caffeine may be the cause of the delayed elimination of theophylline. The present study has indicated that a significant reduction in theophylline metabolism may be caused by a conventional intake of dietary caffeine. In bronchodilator therapy with theophylline, therefore, the daily consumption of caffeine should be taken into consideration. PMID- 8491249 TI - A high incidence of cough in Chinese subjects treated with angiotensin converting enzyme inhibitors. PMID- 8491250 TI - Delayed disposition of adriamycin and its active metabolite in haemodialysis patients. PMID- 8491251 TI - Lack of association between glucose-6-phosphate dehydrogenase deficiency and dextromethorphan O-demethylation polymorphism. PMID- 8491252 TI - Dose proportional absorption of 25-150 mg atenolol. AB - We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested. PMID- 8491254 TI - Molecular cloning and characterization of the angiotensin receptor subtype in porcine aortic smooth muscle. AB - A cDNA encoding porcine aortic smooth muscle angiotensin II (AII) receptor has been isolated using the homology screening approach and sequenced. Specific binding of [125I]AII was found in COS-7 cells transfected with the cDNA (Kd = 0.37 nM, Bmax = 1 approximately 3 x 10(4)/cell) and was displaced with unlabeled AII-related peptides and DUP753 in the order of [Sar1,Ile8]AII = AII > des-Asp1 [Ile8]AII = DUP753 > angiotensin I = angiotensin III. EXP655 had no effect on [125I]AII binding. COS-7 cells transfected with the cDNA responded to AII by only a small increase in the concentration of intracellular free Ca2+. However, electrophysiological study of the receptor expressed in Xenopus laevis oocytes provided strong evidence that it could functionally couple to a second messenger system leading to the mobilization of intracellular stores of Ca2+. Northern blot analysis in cultured porcine aortic smooth muscle cells demonstrated that the expression of this gene varies with the culture media. These results indicate that the cDNA encodes the functional and regulated AT1 subtype of AII receptors. PMID- 8491253 TI - Rabies virus selectively alters 5-HT1 receptor subtypes in rat brain. AB - Rabies virus infection in man induces a series of clinical symptoms, some suggesting involvement of the central serotonergic system. The results of the present study show that, 5 days after rabies virus infection in rat, the total reversible high-affinity binding of [3H]5-HT in the hippocampus is not affected, suggesting that 5-HT1A binding is not altered. 5-HT1B sites identified by [125I]cyanopindolol binding are not affected in the cortex 3 and 5 days after the infection. Accordingly, the cellular inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on the [3H]acetylcholine-evoked release, presumably related to 5-HT1B receptor activity, is not modified 3 days after infection. In contrast, [3H]5-HT binding determined in the presence of drugs masking 5-HT1A, 5-HT1B and 5-HT1C receptors, is markedly (50%) reduced 3 days after the viral infection. These results suggest that 5-HT1D-like receptor subtypes may be affected specifically and at an early stage after rabies viral infection. PMID- 8491255 TI - Dopamine D2 receptors are unevenly distributed in the rat hippocampus and are modulated differently than in striatum. AB - The characteristics of dopamine (DA) D2 receptors were studied in rat hippocampus and for comparison in striatum using the [3H]spiperone radioreceptor assay in vitro. D2 receptors exhibit a bimodal distribution along the length of the hippocampus. Heterogeneity also exists in the transverse axis with high densities in the molecular layers of the subiculum and CA1 plus CA2. As in the striatum, D2 receptors in both dorsal and ventral hippocampus display high and low affinity states for agonists, but all three regions differ with regard to the percentage of receptors in these states. The modulation of these affinity states by GTP, Mg2+ and the iron-chelator, 1,1-O-phenanthroline, differs markedly between dorsal and ventral hippocampus, and between these regions and the striatum. A new model for the modulation of the affinity of D2 receptors for agonists is presented. These data suggest the presence of regional differences in the composition of the D2 receptor-regulatory protein complex. PMID- 8491256 TI - The individual enantiomers of cis-cromakalim possess K+ channel opening activity. AB - Cromakalim (BRL 34915), a racemic trans-3,4-disubstituted benzopyran, is the prototype of a novel group of vasorelaxants which act by opening K+ channels in the cell membrane, the K+ channel openers. The enantiomers of cis-cromakalim were synthesized and their biological activity compared to that of the enantiomers of (trans-)cromakalim. Both the (+)-(3R,4R) enantiomer and its (-)-(3S,4S) antipode inhibited binding of the K+ channel opener [3H]P1075 in strips of rat aorta with pKi values of 5.4 and 5.2, respectively. They relaxed noradrenaline-induced contractions of rat isolated aorta under control conditions with pD2 values of 5.7 and 5.2; their vasorelaxant potency was greatly diminished under depolarized conditions (KCl = 55 mmol/l). Both compounds increased the permeability of the cell membrane for K+ as suggested by their ability to stimulate 86Rb+ efflux from rat aortic strips. The vasorelaxant and the 86Rb+ efflux-stimulating effects of the compounds were inhibited by the sulfonylurea, glibenclamide. These results show that the enantiomers of cis-cromakalim are genuine K+ channel openers. The (R,R) enantiomer is 50 times weaker than the (-)-(3S,4R) enantiomer of cromakalim (= levcromakalim, BRL 38227) but 3 times more potent than the (+)-(3R,4S) enantiomer. These data highlight the importance of the stereochemistry at both the 3 and 4 position of the benzopyran ring. PMID- 8491257 TI - Benzodiazepines increase preprocholecystokinin messenger RNA levels in rat brain. AB - Using in situ hybridisation, the effects of acute and chronic diazepam administration and diazepam withdrawal on preprocholecystokinin (CCK) mRNA levels in discrete regions of rat brain were determined. In cerebral cortex and a subpopulation of hippocampal neurones, CCK mRNA levels were increased after a single injection of diazepam and 24 h after withdrawal from chronic diazepam treatment, but not after chronic diazepam treatment. These results show that, in some neuronal groups, CCK mRNA expression is regulated by benzodiazepines, although there is no clear link between CCK mRNA levels and anxiety state. PMID- 8491258 TI - Molecular changes in erythrocyte membranes induced by long-term administration of clofibrate. AB - It has been reported that an enantiomer ((S)-(-)-4) of clofibric acid, and the racemate, can block the chloride conductance of skeletal muscle membrane. It has also been reported that several analogs of clofibric acid inhibit the HCO3(-)-Cl- exchange of erythrocytes. Since the two effects are probably similar biophysical membrane phenomena, the possibility of a common molecular mechanism arises. We exposed Sprague-Dawley male rats to long-term administration of clofibrate and 20,25-diazacholesterol (20,25-D) for comparison, at equipotent doses. Clofibrate (but not 20,25-diazacholesterol) produced a significant increase in density of the 220,000 Da band (beta-spectrin) and a decrease, also significant, in density of bands 2.1, 2.2, 2.3, 2.6 (syndeins or ankyrins) and of bands 4.1 and 6. Thus, clofibrate exhibits a manifold effect on the protein profile of the erythrocyte membrane cytoskeleton which, due to the lack of effect of 20-25-D, does not seem to be produced by the hypolipidemic effect per se, and thus deserves further study. PMID- 8491259 TI - Gadolinium and neomycin block voltage-sensitive Ca2+ channels without interfering with the Na(+)-Ca2+ antiporter in brain nerve endings. AB - The rare earth lanthanide gadolinium (Gd3+), in concentrations ranging from 1 to 100 microM, reduced the elevation of intracellular Ca2+ concentration [Ca2+]i, monitored by means of the fluorescent probe fura-2. It also decreased the influx of 45Ca2+ through voltage sensitive calcium channels (VSCC), induced by 55 mM K+ in Percoll-purified brain synaptosomes. By contrast, Gd3+ (0.1-30 microM) did not interfere with Na(+)-dependent 45Ca2+ uptake, a process which expresses Na(+) Ca2+ exchange activity. The aminoglycoside neomycin displayed a similar pattern of activity although at higher concentrations (300-1000 microM). At the same range of concentrations (100 and 300 microM), the phenylalkylamine, verapamil, blocked both Ca2+ entry through VSCC and Ca2+ influx through the Na(+)-Ca2+ exchanger. Finally, nimodipine failed to prevent 45Ca2+ influx in either case, and fura-2 monitored [Ca2+]i elevation induced by high K(+)- or Na(+)-dependent 45Ca2+ uptake. Collectively, the data obtained in the present study indicate that Gd3+ and neomycin can be considered to be valid pharmacological tools for selective blocking of VSCC in cerebral nerve terminals, without any concomitant interference with the Na(+)-Ca2+ antiporter, whereas the inhibitory action of verapamil does not discriminate between Ca2+ entry through VSCC or the antiporter. PMID- 8491260 TI - Role of Purkinje cells in the ventral paraflocculus in short-latency ocular following responses. AB - We describe the simple-spike activity of Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of behaving monkeys in association with movements of the visual scene that evoke short-latency ocular following responses. One group of P cells discharged maximally for downward motion, and the other for motion toward the side of the recording. The onset of the simple-spike response was measured in relation to the onset of ocular following in 24 P cells. The majority of P cells (79%) led by 1-9 ms. At the site of each recording, electrical stimuli (single negative pulses, 1.5-45 microA; 0.2 ms in width) were applied and 60% (18/30) of the sites elicited eye movements in the preferred direction of the P cells. The latency of the single-pulse-evoked response in the ipsilateral eye ranged from 8.6 to 10.9 ms. These data suggest that the P cells in the VPFL play a role in ocular following; some discharge early enough to generate the very earliest eye movements. PMID- 8491261 TI - Avian photogenic epilepsy and embryonic brain chimeras: neuronal activity of the adult prosencephalon and mesencephalon. AB - Photogenic genetic epilepsy was studied in an avian model, using either the Fayoumi epileptic chicken (Fepi) or neural chimeras obtained by replacement of embryonic brain vesicles in normal chickens with those of Fepi embryos. In these two kinds of animals motor seizures accompanied by electroencephalographic (EEG) desynchronization and flattening (DF) were evoked by intermittent light stimulation (ILS). In chimeras with only the prosencephalon grafted, motor seizures were less severe but DF remained. ILS-induced DF persisted under paralysis by gallamine triethiodide (Flaxedil). Extracellular recordings were made in the prosencephalon (wulst) and in the mesencephalon (optic tectum) of paralysed animals. Units recorded in the prosencephalon of Fepi and chimeras showed abnormal interictal bursting activity, distinctly different from the non epileptic Fayoumi heterozygotes (Fhtz) and normal chickens. The mesencephalic units of Fepi and chimeras having both prosencephalon and mesencephalon grafted showed two types of abnormal activities during ILS-induced DF, which were distinct from the non-epileptic chickens: type I neurons displaying early, high sensitivity to ILS followed by a prolonged suppression of activity; type II neurons displaying an early and prolonged suppression of activity. The results are discussed with respect to the brain structures generating ictal and interictal EEG activities and motor seizures. PMID- 8491262 TI - Evoked changes of membrane potential in guinea pig sensory neocortical slices: an analysis with voltage-sensitive dyes and a fast optical recording method. AB - Coronal slices from guinea pig visual neocortex were stained with voltage sensitive fluorescent dyes RH414 or RH795. Activity was evoked by electrical stimulation of either white matter or layer I. Emitted-light intensity changes representing summated changes of membrane potential were recorded by a 10 x 10 photodiode array with a temporal resolution of 0.4 ms and a spatial resolution of 60 microns or 94 microns. Following either stimulation of layer I or of white matter, maximal activity was located close to the respective stimulation electrode, in upper layer III/II, and between layer IV and V. With stimulation of the white matter, additional peak activity was recorded from upper layer VI. Non synaptic activity was separated from mixed (synaptic and non-synaptic) activity by comparing responses obtained in standard perfusion medium with those obtained in perfusion medium from which the calcium was omitted, such that synaptic transmission was blocked. With stimulation of the white matter, most of the evoked activity in lower cortical layers was of non-synaptic origin. This non synaptic activity consisted of early and fast potentials, which were predominant in layer VI and probably represented presynaptic fibre activity, and of slower components that were presumably of antidromic origin. Significant postsynaptic activity was only found in upper layer III/II. In contrast, with stimulation of layer I, most of the evoked activity was of postsynaptic origin. Early and fast non-synaptic potentials consisting of presynaptic fibre activity were confined to layer I. Slower non-synaptic activity, that might reflect direct dendritic activation, was minimal and was confined to upper cortical layers. Thus, following either stimulation of layer I or of white matter, the major postsynaptic components were found in upper layer III/II. It is suggested that the postsynaptic response following stimulation of white matter resulted from di- or polysynaptic activation by afferent fibres. The postsynaptic response to stimulation of layer I was presumably a monosynaptic activation of apical dendrites from pyramidal cells by layer I horizontal fibres. Activity following stimulation of white matter spread faster than activity following stimulation of layer I. This might reflect the difference in active conduction along afferent and efferent fibres on the one hand and in passive conductance along the dendritic tree on the other hand. PMID- 8491263 TI - Nerve growth factor-induced excitation of selected neurons in the brain which is blocked by a low-affinity receptor antibody. AB - We have investigated the electrophysiological effects of nerve growth factor (NGF) on single-neuron activity in central nervous system (CNS) grafts of septum, spinal cord, and hippocampus in oculo. NGF was found to have slow-onset, long lasting excitatory effects on the spontaneous firing of neurons in septal grafts, while no such effects were found in neurons of either hippocampal or spinal cord grafts. Pretreatment with an antibody against the p75 low-affinity NGF receptor blocked the NGF-induced excitations. A second NGF application caused much stronger excitatory responses in sensitive neurons. Our data suggest that forebrain cholinergic neurons may be selectively sensitive to NGF also at the neurophysiological level, responding by excitations, and that NGF upregulates these responses within less than an hour. PMID- 8491264 TI - Enhancement of the acoustic startle response by stimulation of an excitatory pathway from the central amygdala/basal nucleus of Meynert to the pontine reticular formation. AB - The acoustic startle response (ASR) is a simple motor reaction to intense and sudden acoustic stimuli. The neural pathway underlying the ASR in rats is already fairly well understood. As the ASR is subject to a variety of modulations, this reaction can serve as a model for vertebrate neuroethologists to investigate the neural mechanisms mediating sensorimotor transfer and their extrinsic modulation. We report here on experiments in rats which were undertaken in order to investigate the neural mechanisms underlying the enhancement of the ASR. An increased amplitude of the ASR can be observed during states of conditioned and unconditioned fear. By employing neuroanatomical tract-tracing methods, we describe a pathway from neurons of the medial division of the central amygdaloid nucleus (cA) and the basal nucleus of Meynert (B) to the caudal pontine reticular nucleus (PnC), an important relay station in the acoustic startle pathway. Extracellular recordings from acoustically responsive neurons in the PnC showed that electrical stimulation of the cA/B facilitates the tone-evoked response of these neurons. Behavioural tests following chemical stimulation of the cA/B with NMDA (N-methyl-d-aspartate) in awake rats indicated that activation of this pathway increases the ASR. The lack of sufficient spatial resolution of our stimulation techniques did not allow us to differentiate the relative contributions of the cA and the B to this effect. As the amygdaloid complex has been implicated in emotional behaviour, particularly in the mediation of fear, these findings substantiate the concept that the amygdaloid complex plays a key role for the enhancement of the ASR by conditioned and unconditioned fear. PMID- 8491265 TI - Medial vestibular nucleus in the guinea-pig: histaminergic receptors. II. An in vivo study. AB - In a companion paper (Serafin et al. 1992) we have demonstrated in vitro that histamine depolarizes three previously described medial vestibular nucleus neuron (MVNn) types (Serafin et al. 1991a, b). It has also been shown that this effect was exclusively mediated through postsynaptic H2 receptors. All the same, the eventual contribution of presynaptic H3 receptors to the physiological response of the MVNn to histamine remained an open question since, during the slicing procedure, any histaminergic axons projecting to the vestibular nuclei would have been interrupted. This rendered our study of H3-mediated effects of histamine difficult. Hence, in the present in vivo study our aim was three-fold: (1) to investigate the presence of H3 receptors at the vestibular nuclei level; (2) to evaluate the functional importance of MVNn H2 receptors; and (3) to explore whether H3 ligands, when injected intraperitoneally (i.p.), could modulate dynamic vestibular functions. In order to address the first two questions, we investigated postural changes induced by perfusion of the guinea-pig's vestibular nuclear complex with specific ligands of the H2 and H3 receptors. Our data extend the conclusions of our in vitro study and suggest that lateral vestibular nuclei neurons and the MVNn are endowed with both H2 and H3 receptors. Our results indicate furthermore that histamine can modulate, quite effectively, static vestibular reflexes. Finally, the present study demonstrates that i.p. injection of thioperamide, an H3 antagonist, induces a significant decrease in the horizontal vestibular-ocular reflex gain and, by contrast to most of the clinically used antihistaminics, has no detrimental effect on the alertness level. Our results may thus lead to clinical testing and use of H3 antagonists as antivertigo or anti motion-sickness drugs. PMID- 8491266 TI - Injections of calmidazolium chloride into the ipsilateral medial vestibular nucleus or fourth ventricle reduce spontaneous ocular nystagmus following unilateral labyrinthectomy in guinea pigs. AB - The effects of three injections (0.5-4.5 h post-operation) of 1-[bis-(p chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4- dichlorobenzyloxy)phenethyl] imidazolium chloride (calmidazolium chloride, R24571), into the ipsilateral medial vestibular nucleus or fourth ventricle, on vestibular compensation for unilateral labyrinthectomy was studied in guinea pigs. R24571, a calmodulin antagonist and inhibitor of several Ca(2+)-dependent enzymes, caused a significant reduction in the average frequency of spontaneous ocular nystagmus (spontaneous nystagmus) during the first 53 h following unilateral labyrinthectomy (n = 5), compared with vehicle-injected animals (n = 5). Although a statistical analysis was not performed on the yaw head tilt and roll head tilt data because of the large variability between animals over the 53-h period of compensation, most R24571-treated animals had less yaw head tilt (4/4 animals) and roll head tilt (4/5 animals) at 9-11 h post-labyrinthectomy than the average values for the vehicle groups at that time. The decrease in the frequency of spontaneous nystagmus following R24571 treatment was not associated with general ataxia or sedation. These results are consistent with recent biochemical studies in suggesting that intracellular pathways associated with Ca2+ may be involved in the neuronal mechanisms of vestibular compensation following unilateral labyrinthectomy. PMID- 8491267 TI - Excitation and inhibition of rat medial vestibular nucleus neurones by 5 hydroxytryptamine. AB - The effects of 5-hydroxytryptamine (5-HT) and related compounds on the discharge rate of tonically active medial vestibular nucleus (MVN) neurones were studied in an in vitro slice preparation of the dorsal brainstem of the rat. The majority (87 of 107, 82%) of MVN neurones were excited by 5-HT. Nine cells (8%) showed a biphasic response to 5-HT, which consisted of a brief inhibition followed by excitation. Eleven cells (10%) were inhibited by 5-HT. The excitatory effects of 5-HT were mimicked by alpha-methyl-5-HT and antagonised by ketanserin and ritanserin, indicating the involvement of the 5-HT2 subtype of 5-HT receptor. In biphasic cells, blockade of 5-HT2 receptors by ketanserin reduced the excitatory component of the response and revealed an enhanced initial inhibition. The inhibitory effects in biphasic cells, and in cells that showed a pure inhibition in response to 5-HT, were blocked by pindobind-5-HT and mimicked by 8-hydroxy-2 (di-n-propylamino)-tetralin indicating the involvement of 5-HT1A receptors. The significance of these findings in relation to the effects of 5-HT on vestibular reflex function is discussed. PMID- 8491268 TI - Responses of single neurons in the hippocampus of the macaque related to recognition memory. AB - In order to analyse how hippocampal activity is related to memory, the activity of single hippocampal neurons was recorded while macaques performed a recognition memory task. In the task, the first time a stimulus was shown, no reward could be obtained, and the second time a visual stimulus was shown, the monkeys could lick to obtain fruit juice. Many other stimuli could intervene between the novel and familiar presentations of each stimulus. Of 660 neurons analysed, 15 (2.3%) responded differently to novel and to familiar stimuli, with the majority of these responding more to novel than to familiar stimuli. The latencies of the differential responses of the neurons were typically in the range 140-260 ms. The responses of these neurons reflected whether a visual stimulus had been seen recently, in that the neurons responded differently to novel and familiar presentations of a stimulus when a median of 21 other stimuli intervened between the novel and familiar presentations. The responses of these neurons were shown to be related to whether the stimuli had been seen before, not to the reinforcement or the lick responses made, in that the neurons did not have comparable responses in a visual discrimination task in which licks were made to a rewarding stimulus but not to another stimulus. It is concluded that the activity of a small but significant proportion of hippocampal neurons is related to whether a stimulus has been seen before recently, and that this processing is likely to be involved in memory. PMID- 8491269 TI - Respiratory-modulated and phrenic afferent-driven neurons in the cervical spinal cord (C4-C6) of the fluorocarbon-perfused guinea pig. AB - The potential contributions of cervical spinal interneurons to the neural control of respiration have been investigated by extracellularly recording the patterns of activity of neurons in the C4-C6 spinal cord during fictive respiration in the fluorocarbon-perfused, adult guinea pig. Two types of neurons were recorded: respiratory-modulated neurons, whose activity was modulated with respiration, and phrenic-driven neurons, which were excited by electrical stimulation of the phrenic nerve. Respiratory-modulated neurons (n = 20) could be divided into inspiratory, expiratory, and phase-spanning neurons, based on their patterns of activity during fictive respiration. Respiratory-modulated neurons showed varying dependencies on the type of breathing; during spontaneous augmented breaths, one half exhibited patterns of activity that were significantly different to those seen during normal, fictive respiration, whereas the other half of the respiratory-modulated neurons showed similar patterns of activity during both normal and augmented breaths. Phrenic-driven neurons (n = 22) could be divided into short-latency (7-12 ms), moderate-latency (12-25 ms), and inhibited neurons, but were only occasionally and weakly modulated with respiration. The results suggest that respiratory-modulated C4-C6 spinal neurons may contribute to the neural control of respiration, with different subpopulations specialized for different types of respiratory tasks, and that phrenic-driven neurons may be interposed in sensory or reflex pathways, such as the spinothalamic tract or phrenic-to-phrenic inhibitory reflex. PMID- 8491270 TI - Do component motions recombine into a moving plaid percept? AB - Two superimposed gratings, which differ in orientation and move independently, combine into a coherently moving plaid if the component gratings are similar. The effect on the plaid motion percept of the addition of texture to each grating was investigated. The texture disambiguates the motion of each component grating. Under the assumption of recombination of first-stage motion detectors into a second stage, which becomes available to perception, one would expect the perceived motion direction of the plaid to change as a result of texture addition. Subjects perceived the oblique motion direction of textured bars of a single orientation correctly. This occurred for texture details with dimensions down to the resolution limit in the fovea (1 min of arc). Two bar patterns with fine texture (1 min of arc details) which differ in orientation were perceived to cohere into a plaid. The plaid's motion direction, however, was independent of the parallel motion components of the bars. For coarser textures (2 and 4 min of arc details) the bar patterns were perceived to slide past one another. In addition, we found that the plaid motion percept occurred less frequently for longer motion sequences, wider bars and for a combination of the component textures at the intersections which is compatible with partial transparency of the bars. These results do not support the two-stage model of Adelson and Movshon (1982), where only the motion component perpendicular to each grating orientation is encoded and where the perception of the plaid motion results from "recombination" of these perpendicular motion components. The data are more in line with a model where first-stage motion detectors are orientation selective but without the restriction that their preferred direction of motion is perpendicular to their preferred orientation. In the second stage it is proposed that combination occurs across the orientation dimension only. This preserves the direction of motion "labels" at the output of the second stage and allows for representation of transparent as well as coherent plaid motion at this stage of processing. PMID- 8491271 TI - Reference systems for coding spatial information in normal subjects and a deafferented patient. AB - To produce accurate goal-directed arm movements, subjects must determine the precise location of target object. Position of extracorporeal objects can be determined using: (a) an egocentric frame of reference, in which the target is localized in relation to the position of the body; and/or (b) an allocentric system, in which target position is determined in relation to stable visual landmarks surrounding the target (Bridgeman 1989; Paillard 1991). The present experiment was based on the premise that (a) the presence of a structured visual environment enables the use of an allocentric frame of reference, and (b) the sole presence of a visual target within a homogeneous background forces the registration of the target location by an egocentric system. Normal subjects and a deafferented patient (i.e., with an impaired egocentric system) pointed to visual targets presented in both visual environments to evaluate the efficiency of the two reference systems. For normals, the visual environment conditions did not affect pointing accuracy. However, kinematic parameters were affected by the presence or absence of a structured visual surrounding. For the deafferented patient, the presence of a structured visual environment permitted a decrease in spatial errors when compared with the unstructured surrounding condition (for movements with or without visual feedback of the trajectory). Overall, results support the existence of an egocentric and an allocentric reference system capable of organizing extracorporeal space during arm movements directed toward visual targets. PMID- 8491272 TI - The role of single touch domes in tactile perception. AB - Detection thresholds to step indentations applied to touch domes were measured and compared with threshold values obtained on adjacent areas of hairy skin. The mean of the detection thresholds determined on touch domes for five subjects was 504 +/- 27 microns (SEM). The detection thresholds found off the touch domes (2-3 mm away) were somewhat higher in all ten cases (two studies per subject), with a mean value of 587 +/- 28 microns, which was significant at the 0.01 level. These thresholds are an order of magnitude greater than those that elicit responses in touch-dome-associated slowly adapting type I (SAI) fibres in cats, and, together with the small difference between the detection thresholds determined on and off touch domes, indicate that the activity of single touch dome SAI fibres does not mediate the detection of steady indentation in the hairy skin. PMID- 8491273 TI - Context dependent amplitude modulations of express and regular saccades in man and monkey. AB - Saccadic reaction times and amplitudes were determined in four human subjects and two rhesus monkeys when they made saccades to visual targets appearing in different spatial or temporal contexts. Two stimuli were presented at different positions, either simultaneously (global condition) or in random order (range condition). Both the gap and the overlap paradigm were used. The characteristics of different groups of saccades defined by the separate peaks in the distribution of the saccadic reaction times as express and regular saccades, were analysed and compared. It is shown that, in man and monkey, the amplitudes of express saccades undergo the same or even stronger context-dependent changes as do those of regular saccades. Furthermore, the presence or absence of the fixation point also influences the saccadic amplitudes, at least for the express saccades. We conclude that the neural mechanisms that determine the amplitudes of the express saccades are more strictly under the control of the physical and physiological conditions of the stimulus situation, whereas regular saccades have greater- although not complete--dependence on the psychological context and, in particular, the subject's effort. PMID- 8491274 TI - Identification of the visual motion area (area V5) in the human brain by dipole source analysis. AB - The retinal periphery of nine healthy subjects was stimulated with computer generated random-dot kinematograms. These stimuli provided almost isolated visual motion information and minimal position cues. Pattern-reversal stimuli at the same location in the visual field were used for control. Stimulus-related electrical brain activity was recorded from 29 scalp electrodes. Total mean and individual data were analyzed with a spatiotemporal multiple dipole model. The scalp potentials showed a different spatial distribution for motion and pattern stimulation in the time range of 160-200 ms. In this epoch, the predominant motion-related source activity was localized in the region of the contralateral occipital-temporal-parietal border. A significant ipsilateral source activity was not found. The predominant source activity related to the pattern stimulus occurred in the same epoch. The corresponding equivalent dipole was localized more medially and deeper in the brain. The orientation of these major dipole activities was markedly different. These dipoles appeared to represent activity of distinct extrastriate areas, in contrast to earlier activity which was modelled by more posterior dipoles in the occipital lobe. The latter dipoles were at comparable contralateral locations and had similar peak activities around 100 ms, suggesting an origin in the striate cortex. PMID- 8491275 TI - Human stance on a sinusoidally translating platform: balance control by feedforward and feedback mechanisms. AB - With subjects standing on a treadmill moving sinusoidally backward and forward, recordings of electromyographic (EMG) leg and trunk muscle activity, head and joint movements and platform torque were made with the subjects' eyes open or closed. The sinusoidal frequency was changed, stepwise and randomly, between 0.5, 0.3 and 0.25 Hz. The amplitude of the deflection was constant at +/- 12 cm. During an adapted sinus cycle, the maximum leg muscle EMG activity was recorded in the tibialis anterior around the posterior turning point and in the gastrocnemius around the anterior turning point in the treadmill cycle. This activity was associated with a forward inclination of the body around the posterior point and a straightening of the body at the anterior point. Both the degree of body inclination and the corresponding EMG activity were dependent upon the sinusoidal frequency. The programmed adjustment of the body inclination was such that the result of inertial and gravitational forces acting on the body coincided with the axis of the body at the posterior turning point. At the anterior point, the adjustment was achieved mainly by strong activation of the leg extensors. The latencies of the compensatory muscle responses to a change in treadmill frequency were significantly shorter at the posterior point for the gastrocnemius than for the tibialis anterior, and at the anterior point for the tibialis anterior than for the gastrocnemius. No correlated changes were seen in the corresponding head and joint movements. The difference in latency can best be attributed to the different body postures during the sinusoid. Early activation of the gastrocnemius is required due to the forward-directed impulse to the inclined body at the posterior point, and of the tibialis anterior muscle due to the backward-directed impulse to the erect body at the anterior point. It is suggested that afferent input from extensor load receptors provides information about the position of the body's centre of gravity relative to the support surface and determines the generation of the EMG responses. Adaptation of both the EMG and biomechanical patterns to a new sinusoidal frequency of the treadmill occurred within four cycles after the change. Biomechanically, this was reflected as a change in the body posture. Vision did not significantly affect these changes. In conclusion, standing on a sinusoidally moving platform, the nervous system acts to control the position of the body's centre of gravity relative to the feet. Body posture is adjusted in such a way that the forces acting on the body during the treadmill movements become minimised.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8491276 TI - Influence of layer V of area 18 of the cat visual cortex on responses of cells in layer V of area 17 to stimuli of high velocity. AB - Focal blockade of restricted regions in layer V of area 18 was used to assess the contribution of this region to the responses to high-velocity stimuli of cells in retinotopically matched, layer V in area 17. In 40% of cases, blockade within area 18 revealed responses of area 17 cells to high-velocity stimuli to which they previously showed only poor responses. Stimulus specificity of the cells in area 17 was otherwise unaltered. All effects were reversible and repeatable. We suggest that a component of the output of layer V from area 18 normally suppresses the responses of retinotopically matched cells within area 17 to stimuli of high velocity, thereby enhancing the specificity of those cells to stimuli of low velocity. PMID- 8491277 TI - Glial populations in the juvenile and adult Mongolian gerbil: relationship to spongiform degeneration of the ventral cochlear nucleus. AB - The gerbil cochlear nucleus is subject to a spongiform degeneration, the progression of which is dependent on auditory functional activity. The most affected region is the ventrolateral aspect of the caudal posterior ventral cochlear nucleus (PVCN). Lesion density and glial changes were quantified in this region for two age groups. Spongiform lesions increased significantly in area density from 4% in 60-day-old gerbils to 14% in 6-month-old gerbils. In spite of this significant increase in tissue damage, no gliosis was found. A significant age-related decrease in oligodendrocyte density was found in the PVCN. PMID- 8491278 TI - Developmental changes of S-100 protein and glial fibrillary acidic protein in the brain in Down syndrome. AB - The location of the gene for the beta subunit of S-100 protein on chromosome 21 suggests that expression may be increased in trisomy 21. Astrocytes from Down syndrome and control patients were examined by immunohistochemistry for the expression of S-100 protein. Adjacent sections were reacted with antisera to glial fibrillary acidic protein to ascertain the presence or absence of astrogliosis. The developmental change in expression of S-100 protein was determined in patients ranging in age from 34 gestational weeks to 57 years. In control patients the number of S-100 protein-immunoreactive cells increased during early infancy to reach a plateau; the number stayed at this level until adulthood and then gradually declined. In Down syndrome, the pattern was similar, except that the number of S-100 protein-positive cells in the hippocampus was greater than in controls, especially during early infancy and at older ages. In the patients examined in early infancy there was no evidence of astrogliosis. However, in older patients with Down syndrome the increased number of immunoreactive cells with antisera to both S-100 protein and glial fibrillary acidic protein indicates the presence of gliosis related to occurrence of senile plaques and neurofibrillary tangles. The increased immunoreactivity of S-100 protein in early life suggests that in trisomy 21 the expression of the gene for the beta subunit may be enhanced. The significance of increased S-100 protein in relation to neural maturation in Down syndrome is unknown. PMID- 8491279 TI - Prenatal expression of 5-HT1C and 5-HT2 receptors in the rat central nervous system. AB - The expression of mRNAs for two 5-HT receptors (5-HT1C, 5-HT2) has been investigated by evaluating in situ hybridization in the prenatal rat CNS. At Embryonic Day 14 (E14), the highest signal for 5-HT1C was found in the choroid plexus, while the marginal/intermediate (m/i) zones of the midbrain, brain stem (including monoaminergic groups), and spinal cord also displayed label. By E18-21 a number of more rostral regions contained transcript, including the hippocampus (CA1), in addition to more intense signal in midbrain, brain stem, and spinal cord. Expression in the choroid plexus appeared to peak between E16-E18, although considerable hybridization signal remained at E21. 5-HT2 transcripts were also detected at E14. Label was present in m/i zones of the midbrain and in a number of other areas. In comparison to 5-HT1C, 5-HT2 mRNA was distributed over a wider rostral-caudal extent at this age. As with 5-HT1C mRNA, signal increased over rostral and brain stem areas at late gestational ages with significant labeling appearing in the olfactory bulb, cerebellum, cortical plate and subplate, hippocampus (dentate gyrus), and monoaminergic nuclei. 5-HT1C and 5-HT2 receptor transcripts were also present over the meninges at E16 and may represent transient expression of these receptors. These expression patterns in the embryonic rat brain, in conjunction with previous evidence indicating that 5-HT can act as a differentiation signal for target neurons, suggests that prenatal 5 HT receptors are positioned to play a role in the prenatal development of the CNS. PMID- 8491280 TI - Levodopa induction of Fos immunoreactivity in rat brain following partial and complete lesions of the substantia nigra. AB - It is controversial whether levodopa (L-DOPA) therapy in the early stages of Parkinson's disease (PD) predisposes to later complications. Partial lesions of the substantia nigra (SN) in rat provide a model of the early stages of PD. We have investigated the potential effects of L-DOPA in early PD by analyzing its influence on the activity of the immediate early gene Fos in the partially lesioned rat. Fos has been used to examine neuronal response to a variety of stimuli in vivo, and L-DOPA is known to increase Fos-like immunoreactivity (FosLI) in striatal neurons after complete lesions of the SN. To determine its effects following partial lesions, we analyzed FosLI in rats given L-DOPA after partial (50-90%) and complete (> 90%) unilateral 6-hydroxydopamine lesions of the SN. Behavioral responses to intraperitoneal injections of apomorphine and amphetamine during life and cell counts of neurons in the SN with tyrosine hydroxylase-like immunoreactivity established the extent of nigral cell loss. FosLI was present in the striatum on the lesioned side predominantly laterally in rats with partial lesions and throughout in rats with complete lesions. Sections counterstained with toluidine blue revealed that only medium-sized striatal neurons displayed FosLI. Prominent FosLI was also found in the ipsilateral piriform cortex and amygdala in both groups and additionally in the ipsilateral zona incerta in the complete group. Therefore L-DOPA induces Fos in the striatum after partial as well as complete SN lesions. This result suggests that L-DOPA induced Fos expression may occur in the early stages of PD and may not require dopamine receptor upregulation, which is believed to develop only in completely lesioned rats and in later stages of PD. The unexpected induction of Fos activity in brain regions besides the striatum suggests that L-DOPA therapy in patients with PD may have more widespread effects than previously anticipated. Since Fos is known to regulate gene transcription, potential alterations in its activity may contribute to the complications associated with L-DOPA therapy in PD. PMID- 8491281 TI - Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. AB - Extracellular pathways circumventing the mammalian blood-brain fluid barriers (e.g., blood-brain and blood-CSF barriers) have been investigated in the rat by immunohistochemical localization of the endogenous serum proteins albumin, IgG, complement C-9, and IgM and by the exogenous tracer protein horseradish peroxidase (HRP). A demonstrable extracellular pathway into the central nervous system (CNS) is evident at the level of the subarachnoid space/pial surface. Immunoreaction products for the serum proteins and reaction product of intravenously administered HRP are identified over the entire pial surface, in the Virchow-Robin spaces and subpial cortical grey matter, and within phagocytes occupying the subarachnoid space/pial surface and perivascular clefts throughout the CNS. From specific circumventricular organs (e.g., median eminence, area postrema, subfornical organ), well known to lie outside the blood-brain barrier (BBB), each of the blood-borne proteins readily enters adjacent white and grey matter and the ventricular system for subsequent rostrocaudal labeling of the ependymal cell lining. Similar immunohistochemical and blood-borne HRP results are obtained in the CNS of the neonatal rat. Peroxidase delivered into the aorta of postmortem adult rats confirms the presence of a BBB in brain sites containing blood vessels impermeable to blood-borne HRP and the absence of a BBB in sites revealed as leaky to blood-borne HRP in the live rat. The results suggest blood borne macromolecules, including those of the immune and complement systems, have potential widespread, extracellular distribution within the CNS and cerebrospinal fluid from sites deficient in a BBB (e.g., subarachnoid space/pial surface, circumventricular organs). These observations may have important clinical implications regarding experimental and pathologic autoimmune dysfunction within the CNS and impact on the interpretation of potential transcytosis of blood-borne peptides and proteins through the cerebral endothelium in vivo. A summary diagram of suspected extracellular and intracellular pathways circumventing the blood brain fluid barriers is provided. PMID- 8491282 TI - Forelimb motor performance following dorsal column, dorsolateral funiculi, or ventrolateral funiculi lesions of the cervical spinal cord in the rat. AB - The neuroanatomical basis of forelimb motor control was examined following various surgical spinal cord lesions in the rat. Focal myelotomies were made at spinal level C4 to determine the effects that damage to long-tract pathways in the dorsal columns, dorsolateral funiculi, and ventrolateral funiculi have on a forelimb reaching and pellet retrieval task. Dorsal column lesions did not significantly reduce retrieval performance but did yield: (i) qualitative alterations in digit use during grasp execution, (ii) targeting errors during reaching attempts, and (iii) an apparent lack of ability to sense the presence of a pellet in the paw. Damage to the dorsolateral funiculi produced significantly diminished pellet retrieval performance at all postlesion intervals due to a prominent grasp deficit involving impaired digit flexion. Lesions of the ventrolateral funiculi did not produce a sustained, significant reduction in retrieval performance, although a qualitative deficit characterized by a mild forelimb reaching hypometria and premature grasp execution was exhibited. Based on comparisons with previous supraspinal and peripheral lesion studies in rats and supraspinal and spinal lesion studies in other mammalian species, the current results indicate that organization of descending and ascending spinal long-tract motor control of the forelimb in the rat is very similar to that described in other mammals, including primates. Additionally, these results demonstrate that the rat can serve as a biomedically relevant model of behavioral impairment and recovery following cervical spinal cord injury. PMID- 8491283 TI - Effects of neonatal thymectomy on the densities of nicotinic cholinergic receptors in skeletal muscle and brain. AB - It has been suggested that the thymic polypeptide thymopoietin interacts with skeletal muscle nicotinic acetylcholine receptors (nAChRs) and brain nicotinic receptors labeled by alpha-bungarotoxin (alpha-BuTX). In this study, the effects of neonatal thymectomy on the density of skeletal muscle nAChRs and the density of brain alpha-BuTX binding sites at 7 and 45 days postnatal were investigated. In addition, the densities of receptors in the skeletal muscle and brain of the athymic nu/nu mouse at 42 days postnatal were measured. We found little evidence that the absence of the thymus alters the density of nicotinic receptors in either skeletal muscle or brain. PMID- 8491284 TI - A new model of photochemically induced acute and reversible demyelination in the peripheral nervous system. AB - Acute photochemical demyelination accompanied by minor axonal degeneration was produced in rat sciatic nerve after topical application of the photosensitive dye Rose Bengal and focal illumination with cold light. Animals were sacrificed at different time periods after challenge and the exposed nerves prepared for light microscopic and ultrastructural evaluation. Important structural changes were already observed at 4-6 h. These included endoneurial swelling, diapedesis of neutrophils and monocytes, vacuolization and vesicularization of Schwann cell cytoplasm, lamellar separation of myelin sheaths, disintegration of axonal microtubules, and accumulation of vesicular material and mitochondria in the axoplasm. Disrupted myelin fragments were phagocytosed by macrophages which penetrated Schwann tubes at Day 3. Schwann cells proliferated and started to enwrap denuded segments of the axon. They were surrounded by redundant basal lamina, thrown into deep folds. Axons remained partly hypertrophic and contained many neurofilaments. A minority showed signs of degeneration. At Days 5-7 denudation was almost complete in the light-exposed nerve area but also in small distal nerve fascicles. After 1 month, axons in the illuminated area and distal to it were completely remyelinated although they had thinner sheaths. Exposure to increased light intensity resulted in deeper lesions and more extended anterograde damage, which also recovered within 1 month. All animals showed rapid functional deterioration which correlated with the severity and extent of structural damage. Recovery was slow and also depended on the degree of histologic damage. Neither control nerves nor sham-exposed nerves revealed signs of structural or functional changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491285 TI - TGF-beta 1 mRNA increases in macrophage/microglial cells of the hippocampus in response to deafferentation and kainic acid-induced neurodegeneration. AB - This study examined TGF-beta 1 mRNA levels and cellular localization in the F344 rat hippocampus following deafferentation or kainic acid (KA)-induced neurodegeneration. By RNA solution hybridization, TGF-beta 1 transcripts were at low prevalence in intact adult rat hippocampus (0.02 pg/microgram total RNA). Four days after unilateral entorhinal cortex lesioning (ECL), TGF-beta 1 mRNA increased threefold in the ipsilateral hippocampus. This increase was localized to the outer molecular layer of the dentate gyrus, where gliosis, synapse loss, and synaptic reorganization occur. TGF-beta 1 mRNA also increased in the hippocampus after KA-induced limbic seizures, particularly in the areas of the hippocampus undergoing neurodegeneration. Microglia [OX-42 immunoreactive (IR) cells] responded to these two lesions with distinct morphological changes. Combined immunocytochemistry-in situ hybridization showed that TGF-beta 1 mRNA was localized to reactive microglia (OX-42-IR, with blunt processes), but not to resting ramified microglia (OX-42-IR, with numerous fine processes) or to astrocytes (GFAP-IR). After ECL, round macrophage-like cells (OX-42-IR with TGF beta 1 mRNA) were seen at the wound site. Thus, brain macrophage/microglial cells produce TGF-beta 1 mRNA in the hippocampus in response to deafferentation and neurodegeneration. PMID- 8491286 TI - Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat. AB - The genetically dystonic (dt) rat is a neurological mutant that displays a movement disorder characterized by repetitive twisting movements of the trunk and limbs. Previous work has identified the cerebellum of the dt rat as a site of biochemical, metabolic, and functional abnormality. In order to test the hypothesis that a cerebellar defect is critical to the expression of the motor syndrome, groups of dt rats and phenotypically normal littermates underwent cerebellectomy (CBX) at either 15 or 20 days of age. The performance of these animals on a battery of motor tasks was compared with their preoperative performance. Age-matched unoperated rats of the same phenotype and a group of dt rats with lesions in the entopeduncular nuclei (ENTO) served as controls. In dt rats, CBX permanently eliminated all motor signs of the disease except pivoting movements without reducing overall levels of activity. In the dt rats, CBX also caused significant improvement in several tests of motor function. The ENTO group, however, showed an increase in motor signs and no improvement in motor function. The results of this study provide the first evidence that the abnormalities detected in the cerebellum of the dt rat are causally related to the motor syndrome and suggest that abnormal cerebellar output may contribute to the expression of motor signs in some human dystonias. PMID- 8491287 TI - The sexual behavior of men in the United States. AB - A nationally representative study of the sexual behavior of men aged 20-39 in the United States shows that the prevalence and frequency of sexual acts (vaginal, anal and oral) and sexual orientation vary by social and demographic characteristics. Analysis of data from 3,321 respondents to the 1991 National Survey of Men reveals that 95% of men have had vaginal intercourse; among them, 23% have had 20 or more vaginal sex partners in their lifetime. About one-fifth of never-married and formerly married men had four or more partners over a recent 18-month period. However, 41% of never-married men and 32% of formerly married men did not have coitus during the four weeks preceding the interview. Only 20% of men have ever engaged in anal intercourse. Among these, 51% had not done so during the previous 18 months, and 90% had not done so during the previous four weeks. Seventy-five percent of men have performed oral sex and 79% have received oral sex, although 53% of men who ever performed oral sex had not done so during the four weeks prior to interview, and only 11% had done so six or more times. The frequency of receiving oral sex is similar. Only 2% of sexually active men aged 20-39 have had any same-gender sexual activity during the last 10 years, and only 1% reported being exclusively homosexual during this interval. PMID- 8491288 TI - Condom use among U.S. men, 1991. AB - A 1991 study of a nationally representative sample of men aged 20-39 finds that 27% of sexually active men had used a condom in the four weeks before interview. Black men are more likely than white men to report condom use (38% vs. 25%), and men younger than 30 are more likely to do so than are those older than 30 (36% vs. 19%). Among white men, condom use increases with years of education; among black men, however, those with 12 years of education are much less likely to report condom use than are those with more or less than 12 years (28% vs. 43 50%). Condom use is positively related to number of partners. Men who have engaged in anal intercourse, those who have had a one-night stand and those who are bisexual or homosexual are also more likely to report condom use. Among those who reported using a condom in the previous four weeks, 55% of whites and 18% of blacks had done so only for birth control and 7% of whites and 9% of blacks had done so only for protection against infection with the human immunodeficiency virus and other sexually transmitted organisms; the remainder had used a condom for both reasons. PMID- 8491289 TI - Perceptions of AIDS risk and severity and their association with risk-related behavior among U.S. men. AB - According to a nationally representative sample of 3,321 men aged 20-39 surveyed in 1991, men appear well aware of the severity of AIDS: Nearly all know that AIDS destroys the immune system and that there is no cure for the disease, but a substantial minority do not think that AIDS will necessarily result in pain and death. Men's perceptions of the disease's severity seem to have little impact on their sexual behavior, with no clear relationship between men's knowledge of AIDS and their recent number of sex acts, their condom use or their participation in anal or casual sex. Men's perceptions of the general risk of human immunodeficiency virus (HIV) transmission also appear to have little impact either on their concerns about AIDS or on their behavior, but their perceptions about the AIDS rate in their local community do affect their concerns and behavior. Men know that certain kinds of behavior place them at risk, and their prior behavior significantly influences their perceptions of their own HIV risk. However, speculation about their own HIV status is only moderately related to their recent sexual behavior. PMID- 8491290 TI - National Survey of Men: design and execution. PMID- 8491292 TI - Towards clearer writing. PMID- 8491291 TI - State legislation on reproductive health in 1992: what was proposed and enacted. PMID- 8491293 TI - Assessment of airways inflammation in chronic bronchitis. PMID- 8491294 TI - Does corticosteroid treatment affect the respiratory muscles? PMID- 8491295 TI - Inhalation challenge in pigeon breeder's disease: BAL fluid changes after 6 hours. AB - The purpose of this study was to determine the cellular events occurring 6 h after bronchial inhalation challenge, in a group of pigeon breeders. Twelve subjects agreed to undergo challenge, either with nebulized pigeon serum (Ps) (n = 10), or with saline (n = 2). The development of characteristic symptoms was used to detect a positive response in combination with monitoring tests (white blood cell count (WBC), body temperature, and spirometry). An initial bronchoalveolar lavage (BAL) was performed before inhalation challenge, and a further BAL on the previously spared right middle lobe subsegment or lingula 6 h after challenge. Paired bronchoalveolar lavage fluid (BALF) samples were analysed for urea, albumin, total and differential WBC, interleukin-1 and interleukin-2. There was a significant increase in total cells, lymphocytes, T-lymphocytes, and neutrophils; numbers.ml-1 of BALF in responders. A monitoring score reflecting severity of patient response correlated with an increase in all cell types (p < 0.05). In conclusion, responders developed both a BALF lymphocytic and neutrophilic "alveolitis" following inhalation challenge, the degree of BALF "alveolitis" correlating with the severity of patient response. PMID- 8491296 TI - Density of phenotypic markers on BAL T-lymphocytes in hypersensitivity pneumonitis, pulmonary sarcoidosis and bronchiolitis obliterans with organizing pneumonia. AB - In vitro studies have shown that the density of surface antigens reflects the degree of activation of T-cells. We therefore studied the density of surface antigens on T-cells from bronchoalveolar lavage fluid (BALF) and blood in patients with sarcoidosis, hypersensitivity pneumonitis (HP) and bronchiolitis obliterans with organizing pneumonia (BOOP). BALF cells were stained with anti CD3, anti-CD4, anti-CD8 and anti-human leucocyte antigen-DR(HLA-DR) monoclonal antibodies, and were analysed by cytoflowmetry. The density was evaluated by measuring the Mean Channel fluorescence intensity of the stained cells. The results demonstrated a significant increase in the CD3 density in patients with hypersensitivity pneumonitis (108.2 +/- 20.2 MC), compared with those with pulmonary sarcoidosis (51.2 +/- 12.6), BOOP (74.5 +/- 29.3), and healthy controls (57.1 +/- 11.5). Similar results were obtained for the CD4 and CD8 density in patients with HP. Although the number of HLA-DR positive cells was increased, the density was lower in patients with sarcoidosis (57.4 +/- 11.6) and hypersensitivity pneumonitis (57.4 +/- 14.8), than in healthy controls (72.2 +/- 15.1). Comparable changes were not observed in the peripheral blood. These results suggest that T-cell activation in hypersensitivity pneumonitis may be associated with an increase in the CD3, CD4, and CD8 density on BALF T-cells. PMID- 8491297 TI - Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils. AB - Synthesis of heat shock proteins (HSPs) is induced in all cells and tissues after exposure to elevated temperatures, or a variety of other types of injury, including oxidative injury. We have previously reported that stress proteins are induced in monocytes-macrophages during phagocytosis of red blood cells. Receptor mediated phagocytosis is associated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Similar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of proteins synthesized by human AMs recovered by bronchoalveolar lavage (BAL) in interstitial lung disease, both under basal conditions and after in vitro exposure to heat or hydrogen peroxide (H2O2). In two out of the 17 cases studied, we observed a high alveolar eosinophilia (10 and 24%, respectively) and phagocytosis, by the AMs, of eosinophilic material. Whereas exposure to heat or H2O2 induced in all AMs the synthesis of the classical HSPs, in these two cases, we found spontaneous synthesis of HSPs and of a 32 kD oxidation-specific stress protein, haeme oxygenase (HO). Exposure of AM to purified eosinophil-derived proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), alone or in combination, did not induce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may represent a new cellular marker of pulmonary injury and eosinophilic inflammation, and an autoprotective mechanism against oxidative stress. PMID- 8491299 TI - Identification of serous-like cells in the surface epithelium of human bronchioles. AB - The conductive airways of the mammalian lung are lined by several morphologically distinct cell types, both ciliated and non-ciliated. Of the non-ciliated secretory cells, mucous (goblet), Clara and neuroendocrine cells have been identified in adult human bronchiolar epithelium but, thus far, the serous cell has not. We have examined human membranous and respiratory bronchioles from macroscopically normal peripheral lung (n = 5 cases). For ultrastructural studies, a minimum of five nucleated, non-ciliated cell profiles, containing electron-dense secretory granules, were selected at random from both bronchiolar levels in each case, such that a total of 60 cells was examined. Data from the computer-aided image analysis of the cells indicated that two populations existed, differing in both granule area and granule number per cell p < 0.0005 by discriminant analysis. By visual inspection, the cells fell neatly into two groups: those which, were predominantly serous-like in type, and those which were "Clara". In the membranous bronchioles, serous-like cells had a mean(SEM) granule area per cell of 3.67(0.62) microns 2 and Clara cells 0.47(0.07) microns 2 (p < 0.001). Also, in the membranous bronchiole, the mean(SEM) number of granules in serous-like cells was 40(4.7) and in Clara cells 10(1.1) (p < 0.001). At the respiratory bronchiolar level, the corresponding means were similar to those of the membranous bronchioles and, likewise, serous and Clara cells were significantly different. Thus, our data, indicate that serous cells are present in the adult human bronchiole. PMID- 8491298 TI - Changes in bronchoalveolar lavage inflammatory cells in asthmatic patients treated with high dose inhaled beclomethasone dipropionate. AB - Using serial bronchoalveolar lavage (BAL), we have studied changes in the airway inflammatory cell populations in 20 asthmatic patients, before and after treatment with inhaled beclomethasone dipropionate (BDP), 2,000 micrograms daily in an uncontrolled study. There was a significant improvement in asthma severity, as measured by symptom score and airways responsiveness, and there were significant reductions in the total BAL eosinophil, epithelial cell and mast cell counts, with a significant increase in the percentage BAL lymphocyte count. No significant correlations were found between the changes in airway inflammatory cell numbers and the reduction in asthma severity. In contrast, the fall in ROS generation by the pulmonary macrophage and granulocyte populations was nonsignificant, but the improvement in airways responsiveness was positively correlated to the reduction in the unstimulated pulmonary macrophage activity. Although these data are uncontrolled, the results are compatible with previous studies in suggesting an effect of steroids on the eosinophil, mast cell and epithelial cell in asthmatic airways. They also highlight the probable importance of the luminal lymphocyte population and pulmonary macrophage activation within the asthmatic airway, the beneficial modulatory effect of inhaled BDP treatment upon them, and the relative steroid-resistance of pulmonary inflammatory cell activity. PMID- 8491300 TI - Skin reactivity and eosinophil count in relation to the outcome of childhood asthma. AB - The aim of this study was to determine whether an association can be found between childhood skin reactivity and the outcome of asthma in young adulthood in a group of 406 asthmatic children, of whom 348 (86%) could be followed up in adulthood. A complete data set on skin tests and eosinophil count was available in 259 allergic subjects. They were stratified into three classes, according to initial skin test score in childhood. An increase in skin reactivity was noted from childhood to adulthood, while the differences in skin reactivity between the three classes remained significant. In childhood, a marked difference in total eosinophil count was found between the classes. Towards adulthood, a decrease in eosinophil count was noted, and the differences between the classes were no longer significant. The children with lowest skin reactivity also had the lowest symptom score in childhood. In adulthood, the prevalence of respiratory symptoms in this class was lower than in the other two classes. The prevalence of bronchial responsiveness to histamine was lowest in subjects with the lowest skin test score in childhood. Ventilatory parameters revealed no differences between the three classes. We conclude that although a low skin reactivity in childhood might be associated with a relatively favourable prognosis for asthma symptoms in adulthood, there is only limited evidence to support this hypothesis in our study. PMID- 8491301 TI - Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children. AB - To investigate whether dietary salt intake and urinary sodium and potassium levels are related to respiratory symptoms and bronchial responsiveness, a cross sectional study among 2593 subjects aged 9 to 16 was conducted in four communities of the Latium region (Italy). Questionnaires were administered to the parents, urine samples were collected, lung function, methacholine challenge tests and prick tests were performed. Information about familial and personal dietary salt use and respiratory health was collected from the parents of 2439 (94%) subjects. A total of 2020 methacholine challenge tests and 916 urinary sodium and potassium levels were available for analysis. Personal table salt use was strongly related to cough and phlegm apart from colds (adjusted odds ratios, OR, 1.87, 95% confidence intervals, CI, 1.20-2.90), wheezing apart from colds (OR, 2.19, 95% CI, 1.27-3.77), wheezing with dyspnoea (OR, 1.45, 95% CI, 0.98 2.12) and wheezing after exercise (OR, 2.16, 95% CI, 1.35-3.44). These associations were mainly found in boys. Use of familial table salt and canned food showed no relation to respiratory symptoms. Increased bronchial responsiveness was associated with a higher urinary potassium excretion in boys, but not with urinary sodium. In conclusion, personal table salt use is related to an increased prevalence of bronchial symptoms; an increase in bronchial responsiveness among those with higher potassium excretion also seems to be implied. Although it is difficult to interpret the results of this study in causal terms, the findings might be relevant to the distribution of bronchial symptoms and diseases in the population. PMID- 8491302 TI - No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study. AB - We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate, in 17 asthmatic children aged 6-12 yrs (mean 9 yrs). Placebo, 2, 4 and 6 mg terbutaline were given b.i.d. for 14 days, in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline.day-1, respectively. There was no correlation between plasma terbutaline and dose of terbutaline. A small but statistically significant dose-related increase in morning and evening peak expiratory flow (PEF) recordings occurred, but the incidence of side-effects also increased with the dose given. There was a trend towards more side-effects when the high doses were used, and two patients withdrew from the study because of side-effects at this dose. It is concluded that continuous treatment, even with high doses of oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID- 8491303 TI - Snoring, asthma and sleep disturbance in Britain: a community-based survey. AB - A questionnaire was sent to a random sample of adults in eight locations throughout Britain, to investigate the prevalence of snoring, asthma and sleep complaints in community-based British adult. Of the 1,478 respondents (831 females, 647 males; mean +/- SD age 45 +/- 18 yrs), 37% reported snoring at least occasionally, and 11% reported snoring on at least four nights per week (frequent snorers). Frequent snorers reported spending less time asleep at night, falling asleep accidentally during the day more often, taking planned daytime naps, and falling asleep whilst driving or operating machinery more often than the other respondent. Using ordinal logistic regression analysis to allow for the age and sex of the respondents, both accidental daytime sleep and planned daytime naps were commoner in frequent snorers than other respondents. Six percent of all respondents and 6% of those aged under 40 yrs reported that they had asthma (asthmatics). Seven percent of respondents aged less than 40 yrs reported wheezing on three or more occasions per year, and had been prescribed oral or inhaled bronchodilators (young wheezers). More than 80% of the asthmatic respondents of all ages, and young wheezers, reported waking at night with wheeze at least occasionally, and more than 30% of each group reported this symptom frequently. A larger proportion of asthmatics and young wheezers reported that their night-time sleep was unrefreshing, and that they had too little sleep at night than the other respondents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491304 TI - Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma. AB - The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness (AMS) and on overnight oxygenation, in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma, 6 males and 10 females, mean age 32 yrs, were first investigated at low altitude (760 m). They presented with mild airways obstruction, normal arterial blood gases, and normal oxygenation at night studied by pulse oximetry. After initial investigations, patients were divided by random number into the treated (T) and control (C) groups of eight patients each. T group patients received acetazolamide, 750 mg daily for 2 days, before the ascent and on the first day at altitude (3,200 m). Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry, performed on the first night at altitude, revealed that group T patients had statistically higher (p < 0.05) initial, 91 vs 87%, mean, 90 vs 86%, and minimum, 84 vs 75%, arterial oxygen saturation than group C patients. Overnight pulse oximetry was repeated on the 5th, 10th and 17th day at altitude, and showed that in group C patients, from the 5th day onwards, oxygenation improved to the level observed in group T patients on the first night. We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS, and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia. PMID- 8491305 TI - Differences between sniff mouth pressures and static maximal inspiratory mouth pressures. AB - Measurements of static maximal inspiratory mouth pressure (PImax) and dynamic sniff mouth pressure (Psniff) are frequently used to assess inspiratory muscle strength. The aim of the present study was to examine, in 42 healthy subjects, the equivalence of PImax and Psniff, the influence of body posture on PImax and Psniff, and the effects of nasal patency and repeated manoeuvres on Psniff. PImax was significantly higher than Psniff, 11.05 +/- 0.42 versus 8.53 +/- 0.31 kPa. Because of the low agreement between PImax and Psniff, the two measurement methods were not interchangeable. The limits of agreement were 2.56 +/- 3.92 kPa. Sitting PImax was 11.05 +/- 0.42 kPa, and supine PImax was 9.36 +/- 0.41 kPa. Sitting and supine Psniff were 8.53 +/- 0.31 kPa and 7.52 +/- 0.33 kPa, respectively. Psniff performed with one nostril open instead of two, was higher: 9.67 +/- 0.32 kPa left and 9.62 +/- 0.32 kPa right versus 8.53 +/- 0.31 kPa when both nostrils were open. After 20-28 sniff manoeuvres, Psniff fell from 8.43 +/- 0.31 kPa to 7.83 +/- 0.30 kPa, suggesting some mechanism of inspiratory muscle fatigue. We conclude that measurement of sitting PImax yields the highest values for inspiratory muscle strength. The two measurement methods, Psniff and PImax, are not interchangeable. Measurement of Psniff is affected by nasal patency. PMID- 8491306 TI - Respiration after phrenicotomy and hydrocortisone treatment in anaesthetized rats. AB - The study was designed to determine the extent to which respiratory muscle wasting, resulting from corticosteroid-induced atrophy, may affect respiration in normal rats and in rats with denervated diaphragm. Twenty four male Wistar rats were divided into four groups: 1) controls with sham operation (SX) and vehicle injections: 2) SX with eight hydrocortisone (HC) injections (60 mg.kg-1.day-1 i.m.); 3) phrenicotomized (PX), injected with vehicle; 4) PX and HC-treated. HC treatment was started on the thirteenth day after surgery. Under urethane anaesthesia, tidal volume, respiratory rate, arterial carbon dioxide tension (PaCO2) and occlusion pressure were measured at rest and after 5 min of stimulated-breathing induced by added dead space 22nd day after surgery. All HC treated animals decreased body weight by 32% compared to untreated rats. The diaphragm weight was reduced in PX rats by 29%, and after HC by 44%, while in PX rats with HC treatment diaphragm weight decreased by only 21%. PX rats (HC untreated) had the lowest minute ventilation and occlusion pressure. There was no difference in ventilation between control and both HC-treated groups at rest. However, ventilation in PX and HC-treated rats did not increase upon stimulation, and the occlusion pressure increased significantly only in the HC-untreated animals. We conclude that in the rat, HC treatment did not affect resting ventilation, but it impaired ventilation performance, during increased demand, in animals handicapped by diaphragm denervation. PMID- 8491307 TI - Assessment of the respiratory compliance in awake subjects using pressure support. AB - Pressure support (PS), a new mode of ventilatory assistance, is known to induce respiratory muscle relaxation. It was used to obtain reliable measurements of the compliance of the respiratory system (Crs) in awake subjects. PS was applied, through a mouthpiece, at four successive levels (0, 0.75, 1 and 1.25 kPa) to 30 healthy subjects. At the highest PS level, the subject's relaxation was obtained as assessed by a decrease in the occlusion pressure from 0.10 +/- 0.06 to 0.05 +/ 0.04 kPa, whereas the minute ventilation increased (from 7.5 +/- 1.5 to 13.8 +/- 3.3 l.min-1), and the end-tidal carbon dioxide tension (PCO2) decreased (from 5.0 +/- 0.4 to 3.2 +/- 0.5 kPa) below its apnoea threshold. In three subjects, respiratory muscle relaxation was confirmed by a fall in diaphragmatic electromyographic activity. Crs was calculated as the ratio of the tidal volume to the corresponding end-inspiratory airway pressure (i.e. PS level) since, at end inspiration, a zero-flow period was obtained. Crs was highly correlated (r = 0.77) to the height (Ht) of the subjects: Crs (l.kPa-1) = 3.56 x Ht (m) -4.86 (+/ 0.23), allowing normal values to be determined. In order to evaluate the applicability of the method to patients, Crs was measured in four patients with scoliosis, and was found to range from 45-82% of the predicted values. It is suggested that this simple method of Crs determination may be used to characterize various chest wall or pulmonary diseases. PMID- 8491308 TI - Value of pulse oximetry in screening for long-term oxygen therapy requirement. AB - Pulse oximetry, combined with spirometry, was evaluated as a method of selecting chronic obstructive pulmonary disease (COPD) out-patients requiring definitive arterial blood gas analysis for long-term oxygen therapy (LTOT) assessment. A relatively high screening arterial oxygen saturation by pulse oximetry (SaO2) level was set, in order to maximize sensitivity. All 113 COPD out-patients attending the hospital clinic over a 6 month period were screened. Sixty had a forced expiratory volume in one second < 1.5 l and 26 had an SaO2 < or = 92%. These 26 underwent arterial blood gas analysis. Nine had an arterial oxygen tension < 7.3 kPa all with an arterial carbon dioxide tension (PaCO2) > 6 kPa. A further eight had a PaO2 < 8 kPa. This produced a sensitivity of 100% and specificity of 69% for oximetry in the detection of PaO2 < 7.3 kPa determined by direct arterial puncture and 100% and 86% respectively for detecting a PaO2 < 8 kPa. Although the poor specificity of oximetry in the crucial PaO2 range makes it unsuitable, when used alone, for prescription of LTOT, it may prove valuable in selecting patients who require further definitive arterial blood gas analysis. PMID- 8491309 TI - Hiccup in adults: an overview. AB - Hiccup is a forceful, involuntary inspiration commonly experienced by fetuses, children and adults. Its purpose is unknown and its pathophysiology still poorly understood. Short hiccup bouts are mostly associated with gastric distention or alcohol intake, resolve spontaneously or with simple folk remedies and do not require medical attention. In contrast, prolonged hiccup is a rare but disabling condition which can induce depression, weight loss and sleep deprivation. A wide variety of pathological conditions can cause chronic hiccup: myocardial infarction, brain tumour, renal failure, prostate cancer, abdominal surgery etc. Detailed medical history and physical examinations will often guide diagnostic investigations (abdominal ultrasound, chest or brain CT scan...). Gastric and duodenal ulcers, gastritis, oesophageal reflux and oesophagitis are commonly observed in chronic hiccup patients and upper gastrointestinal investigations (endoscopy, pH monitoring and manometry) should be included in the diagnostic evaluation systematically. Etiological treatment is not always available and chronic hiccup treatment has classically relied on metoclopramide and chlorpromazine. Recently, baclofen (LIORESAL) has emerged as a safe and often effective treatment. PMID- 8491310 TI - Central sleep apnoea syndrome with upper airway collapse. AB - We report on an 83 yr old man with hypersomnia and central sleep apnoea (CSA). He had several possible causes for CSA, including a central nervous system lesion, hypocapnia and anatomical narrowing of the airway at the hypopharyngeal level. We postulate that reduced central respiratory drive occurring in conjunction with upper airway narrowing may have led to central apnoeas. These in turn could have facilitated a complete passive hypopharyngeal collapse at the end of each apnoea, as visualized by somnofluoroscopy. The CSA could also have been favoured by respiratory instability due to chronic hypocapnia. PMID- 8491311 TI - Pulmonary veno-occlusive disease and Hodgkin's lymphoma. AB - Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension, and is of unknown aetiology. It has seldom been described in association with malignant disease and cytotoxic chemotherapy, and there have been only two previous reports of an association with Hodgkin's disease [1, 2]. We report a third case which developed 14 yrs after Hodgkin's disease had been diagnosed and treated, initially with radiotherapy and subsequently with chemotherapy. PMID- 8491312 TI - Long-term nasal ventilation in neuromuscular disorders: report of a consensus conference. AB - Following the colloquium entitled "Nasal Ventilation and Neuromuscular Disease", which took place in Lyon, France, October 24, 1991, a group of authorities on neuromuscular disorders met to establish a consensus concerning the application of this technique, in the clinical setting, for patients with Duchenne's muscular dystrophy, non-Duchenne myopathies and the spinal muscular atrophies. This report summarizes recommendations issuing from this conference. The conclusions drawn from this work should not be applied to patients with other diagnoses. PMID- 8491313 TI - The importance of magnetic resonance spectroscopy in surgical oncology. PMID- 8491315 TI - Breast cancer surgery in 30 Italian general hospitals. AB - The utilization of limited surgery in patients with breast cancer operated between September 1986 and July 1988 was assessed using information collected within a cohort subsequently enrolled in a randomized clinical trial testing the efficacy of post-surgical follow up. Overall 30% had limited surgery, 61% had other more radical procedures and 9% are still undergoing an unnecessary Halsted mastectomy. Several factors were related to the lower likelihood of getting a conservative procedure: geographic distribution, age, level of education, quadrant and nodal state. The paper discusses the implications of these findings in view of the otherwise growing consensus that more radical surgery should be abandoned. PMID- 8491314 TI - Early changes in the 1H-NMR plasma spectrum in patients following breast surgery. AB - The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H-nuclear magnetic resonance (NMR) spectrum were analysed in plasma samples drawn pre- and post-surgery from patients treated for benign or malignant breast tumor. Using a 500 MHz NMR instrument operating at 25 degrees C, the resonances were analysed for line width at half-height and then averaged. The amounts of triglyceride (TG), cholesterol, apolipoproteins A1 (ApoA1) and B (ApoB) were measured in each sample. One week post-surgery, the high-field shoulder of the aliphatic peaks decreased and the composite peaks were weighted down-field compared with spectra obtained pre-surgery. The average line width in patients with malignant tumor observed 1 week post-surgery was narrower than pre surgery (30.5 +/- 3.9 vs 38.1 +/- 4.2 Hz) (P = 0.01). Line widths observed 1 day post-surgery were not significantly different from pre-surgery values in either patient group. Comparing the methylene and methyl composite peaks, the narrowing in line width observed 1 week post-surgery was more pronounced for the methylene than the methyl line width. The ratio between the height of the composite methylene and methyl peaks was higher 1 week post-surgery (ratio, 2.12 +/- 0.23) than pre-surgery (1.79 +/- 0.37) (P = 0.03), indicative of a relative increase in triglyceride-rich lipoproteins. Compared with pre-surgery levels, TG was higher (1.8 +/- 0.3 vs 1.5 +/- 0.4 mmol/l) (P = 0.05) and ApoA1 lower (1.32 +/- 0.14 vs 1.43 +/- 0.12 g/l) (P = 0.02) 1 week post-surgery. One day post-surgery, decreased levels of lipids and apoliproteins were found. In conclusion, the line narrowing is explained as an effect of the surgical trauma itself. A less contribution to the composite line from high-density (HDL) relative to very-low density (VLDL) lipoprotein is suggested as one mechanism for line width narrowing observed after surgery. PMID- 8491316 TI - Axillary nodal status in women with screen-detected breast cancer. AB - A prospective study of the axillary nodal status of women found to have an invasive breast cancer within the prevalence screening round is reported. Thirty one per cent of patients were lymph node positive. Twenty-two per cent of patients with an impalpable tumour and 41% of those with a palpable tumour had involved axillary lymph nodes. Only 6% of patients with a tumour of less than 10 mm had diseased axillary nodes. Of the factors examined only the size of the invasive component of the primary tumour was related to the axillary lymph node status. This proportion of patients with positive lymph nodes is higher than might be expected and is likely to represent those patients with potentially symptomatic breast tumours detected by breast screening in the first round. PMID- 8491317 TI - Parathyroid hormone related protein in breast cancers of widely varying prognosis. AB - Parathyroid hormone related protein (PTHrP) is a novel calcium regulating hormone that may have a significant role in the pathophysiology of breast cancer. We have previously demonstrated a relationship between immunohistochemically detectable PTHrP in primary breast tumours and the subsequent development of bone metastases and hypercalcaemia. The aim of this study was to compare the PTHrP status in the primary tumours from three groups of patients with widely varying prognosis. (1) The favourable outcome group; all patients had a favourable prognosis and minimum 3 years disease free follow up (n = 30). (2) The unfavourable outcome group; all patients presented with localized breast cancer but developed distant disease within 3 years (n = 26). (3) The unfavourable presentation group; all had distant disease at first presentation (n = 26). No differences in PTHrP status of the primary tumour amongst the three patient groups were found (66%, 65% and 61% positive respectively). The development of bone with liver metastases and hypercalcaemia was associated with increased positive PTHrP status of the primary tumor. PMID- 8491318 TI - Effect of closing dead space on seroma formation after mastectomy--a prospective randomized clinical trial. AB - To evaluate the effect of closing dead space on seroma formation after mastectomy, 39 patients undergoing 40 mastectomies with axillary node clearance were randomized to undergo suturing of skin flaps to underlying muscle or conventional skin closure. Duration of closed suction drainage, 72 h, and shoulder exercises, commencing on the first post-operative day, were standardized for both groups. Closed suction drainage was significantly less (P < 0.05) in the group that had flaps sutured, 272 +/- 46 ml vs 393 +/- 39 ml. Also fewer patients in the flap sutured group developed seromas, 5 (25%) vs 17 (85%) chi 2 = 12.2 P < 0.001. Three patients in the group that had conventional skin closure had breakdown of wound edges, two developing a prolonged serous discharge, while none occurred in the sutured group. A functional range of shoulder motion was attained at 6 months in 14 (70%) patients in the flap sutured group compared with nine (45%) in the conventional skin closure group (P = NS). These results confirm the value of suturing skin flaps to underlying muscle in reducing local morbidity after mastectomy and suggest that this technique should be included in the closure of all mastectomy wounds. PMID- 8491319 TI - Comparing surgical resection of limited hepatic metastases from colorectal cancer to non-operative treatment. AB - The survival of two groups of patients, affected by liver metastases (Stage I and II by Gennari et al.) from a previously operated colorectal cancer and treated by surgical resection (Group 1, 39 patients) or chemotherapy with various cytotoxic drugs (Group 2, 31 patients) at the Istituto Nazionale Tumori, Milan, is reported. In comparison with Group 2, Group 1 included more patients with metachronous lesions, with high level of serum bilirubin and with primary tumour originating from the colon. A univariate analysis (log rank test) identified a statistically significant prognostic role of type of treatment (surgery vs chemotherapy) and of the level of serum bilirubin. However the multivariate analysis by the Cox's regression model showed that the only independent statistically significant prognostic factor was type of treatment, since the hazard ratio of surgery vs chemotherapy was 0.490 with a 95% confidence interval of 0.256-0.936. The survival probabilities at 24 and 36 months were respectively 60% and 47% in surgical patients, vs 30% and 23% in those receiving chemotherapy, the difference between the curves being statistically different (P = 0.001). The median survival of Group 1 patients was 30 months whereas the median survival of Group 2 patients was 19 months, a value quite similar to that published in literature for untreated patients with limited metastatic disease-thus indicating that this patients' population was not selected according to unfavourable criteria. These findings suggest a beneficial role of surgical resection in patients with colorectal metastases confined to the liver in Stages I and II. PMID- 8491320 TI - Somatostatin inhibits both in-vitro and in-vivo carcinoembryonic antigen secretion by human colon cancer. AB - This study investigated the effect of SMS 201.995 on CEA secretion of human colon cancer cell lines in vitro and as xenografts in nude mice. Using the two cell lines which secreted significant amounts of CEA in the media, there was a 40% and 54% decrease in CEA level at 2e-10M and 2e-9M concentrations of SMS 201.995, respectively, after five days of incubation for LIM 2412 cell line (P < 0.05, both). There was a 13% decrease in CEA at 2e-9M concentration of SMS with the LoVo cell line (P > 0.05). In vivo, there was a direct correlation between the mean volume of the LIM 2412 xenografts and serum CEA level (r = 0.92). When the growth of xenografts was inhibited by SMS, there was a corresponding drop in serum CEA. On the other hand, when tumor sizes remained unchanged, whether after a short duration of SMS treatment or with the oral route, serum CEA was unaffected. Thus, CEA concentration reflected cell number in vitro and tumor size in vivo as a response to treatment with SMS 201.995. The CEA level may therefore be a useful marker during somatostatin treatment to monitor tumor response. PMID- 8491321 TI - Treatment of cutaneous metastases from malignant melanoma using the carbon dioxide laser. AB - Between October 1988 and September 1991, 60 patients with cutaneous metastases from malignant melanoma have been treated palliatively using carbon-dioxide laser ablation. The number of lesions per patient varied between 3 and 450; accordingly treatment was performed under local or general anaesthesia. The post-operative complication rate was low and the majority of wounds healed within 6 weeks. Control of in-transit metastatic disease and palliation of disseminated cutaneous melanoma can be achieved by carbon-dioxide laser ablation which provides a simple and effective alternative to isolated limb perfusion. Eighteen of the 32 patients in this series with stage IIIa disease were controlled by three or fewer laser treatments in the first year. We advocate laser vaporization as the initial treatment for non-nodal regional recurrence in the knowledge that isolated limb perfusion can be offered at a later stage for patients who cannot be controlled by the laser. PMID- 8491322 TI - Prevertebral fascia flap in hypopharyngeal reconstruction: a preliminary report. AB - Ablative surgery for pyriform sinus cancer often leaves a defect which cannot be closed primarily. Many techniques for hypopharyngeal reconstruction have been described but no single technique can be recommended for use in all situations. The prevertebral fascia flap described in this article provides an alternative to hypopharyngeal repair when a more complex technique is contra-indicated. It is a one stage procedure, fashioned with locally available tissue, and technically simple. Its use in two anecdotal cases is described herewith. PMID- 8491323 TI - Female sexual functioning after radical surgical treatment of rectal and bladder cancer. AB - A computer-based search for literature on female sexual functioning after radical cystectomy and rectal cancer surgery revealed 11 articles. Although some prognostic variables are presented in the literature (age, the magnitude of surgery, hand-made vs stapled anastomoses, nerve content in the surgical specimen) there are very few definitive answers to the questions regarding which internal and external causal factors elicit and control sexual functioning after radical pelvic surgery. The review is concluded by some guidelines to help patients and their partners cope with sexual problems. PMID- 8491324 TI - Bilateral localized Castleman disease of the retroperitoneum. AB - A case report of a 23-year-old patient with abdominal pain was found to have a bilateral, retroperitoneal localized form of Castleman disease. To the best of our knowledge, it is the first report of a bilateral form described in the literature. Surgical excision resulted in the disappearance of symptoms and both masses were found to be of the hyaline type. Follow-up computerized tomography revealed no pathological sequelae. PMID- 8491325 TI - Needle biopsy of breast cancer. Appearance of tumour cells along the needle track. AB - Appearance of tumour cells along the needle track in patients with breast cancer diagnosed by SURECUT needle biopsy is found in two out of 47 consecutive cases. It is not known whether these cells are early implantation metastases or are harmless. To avoid any unnecessary risk to the patients, we recommend that needle biopsy is so performed, that it is possible to remove the track during the definite surgical procedure, and that penetration into the muscles of the thoracic wall during the biopsy procedure is avoided. PMID- 8491326 TI - Endodermal sinus tumour of the vulva: an interesting clinico-pathological problem. AB - Endodermal sinus tumours (EST) of the lower female genital tract are uncommon malignancies. The majority of these involve the vagina and cervix, though there are a few case reports of tumours involving the vulva. These are usually either locally advanced or have metastatic disease present at initial diagnosis, and generally do badly on treatment. This case report discusses primary vulval involvement by EST. It shows that the absence of tumour markers can be misleading, and discusses the role of radiation and chemotherapy in the treatment of this rare disease. PMID- 8491327 TI - Clear cell sarcoma (malignant melanoma of soft parts). Presentation of two additional cases. AB - Clear cell sarcoma or malignant melanoma of soft parts is a rare tumor with a predilection for the extremities. Although characterized by a slow clinical course, prognosis is poor because of a high incidence of local recurrences and distant metastases. In this report, two additional cases which originated in the toes are presented. PMID- 8491328 TI - A randomized trial of three methods of obtaining Papanicolaou smears. AB - In a randomized study three methods of obtaining cells for Papanicolaou smears were tested: the classical Ayre spatula, the Ayre spatula plus the endocervical cytobrush and the cervexbrush. Endocervical cells were identified in 67.8% of smears obtained with the Ayre spatula alone, in 89.1% of smears obtained with the Ayre spatula plus the endocervical cytobrush and in 85.6% of smears obtained with the cervexbrush. The use of the Ayre spatula alone for obtaining cervical cells for Papanicolaou smears is discouraged. PMID- 8491329 TI - Chlamydia trachomatis in infertile Greek women. A serologic and laparoscopic study. AB - This study investigates the prevalence of antichlamydial antibodies in infertile women, who underwent diagnostic laparoscopy. The patients were divided into two groups based on the presence or absence of damage of the fallopian tubes. Antichlamydial IgG antibodies were found in 22 of 27 (81.5%) infertile women with damaged fallopian tubes and 10 of 23 (43.5%) women with normal tubes. Mean geometric IgG titres for C. trachomatis were significantly higher in the patients with damaged tubes (187.4 vs. 39.39). C. trachomatis was not isolated from the peritoneal fluids. Only two chlamydial cultures of cervical specimens were positive, one in each group. These findings confirm that C. trachomatis may be a major cause of tubal damage with resultant infertility. PMID- 8491330 TI - Persistence of antichlamydial antibodies after treatment of acute salpingitis with doxycycline. AB - The effect of treatment with doxycycline on serum IgG and IgA antichlamydial antibodies was evaluated in 33 women who had had acute salpingitis associated with high titers of serum IgG (> or = 1:128) and/or IgA (> or = 1:16) antichlamydial antibodies. Overall, 29 women (87.9%) remained with high titers of IgG and/or IgA antibodies. No change or insignificant change in IgG antibody titer was demonstrated in 21 women (63.6%) and in IgA antibody titer in 21 women (63.6%). Positive seroconversion or a significant increase (> or = 4-fold) in IgG antibody titer was demonstrated in eight women (24.2%) and in IgA antibody titer in six women (18.1%). Negative seroconversion or a significant decrease in IgG antibody titer was demonstrated in four women (12.1%) and in IgA antibody titer in six women (18.1%). It is concluded that in most patients who had acute salpingitis associated with pretreatment high titers of serum antichlamydial antibodies, posttreatment titers may remain high even if treatment with doxycycline results in complete resolution of clinical signs and symptoms of the disease. PMID- 8491331 TI - Preliminary report of unexpected local reactions to a progestogen-releasing contraceptive vaginal ring. AB - This is the first report of vaginal erythematous areas associated with the use of a levonorgestrel-releasing contraceptive ring. Of 139 female subjects, 48 developed lesions of varying size and degrees of redness. Sixteen of these have undergone serial colposcopy and thirteen have also had biopsy examinations, which revealed acetowhite areas and, histologically, chronic inflammation with widely dilated vessels and frequently with thinning of the epithelium. The cause remains uncertain but hormonal, chemical and physical effects might all have a role. PMID- 8491332 TI - Appraisal of in vitro fertilization. AB - In-vitro fertilization and embryo transfer techniques are now used all over the world (53 countries). The results of 492 of all world units were collected from national surveys and registries of different countries. Since 1985, more than 53,635 women were treated and 34,316 babies were born by 224,473 treatment cycles, followed by more than 160,518 transfer cycles. Only about 65%-75% of all resulting pregnancies attained live births. The remainder ended with spontaneous abortions (26%), or ectopic pregnancies (5.54%). The multiple pregnancy rate (22%) was higher than the normal population and contributed to higher rates of preterm deliveries and perinatal mortality. No increased incidence of chromosomal aberrations and malformations were noted during the years (2.25%). Success rates did not improve significantly within the 5-year period surveyed, in most parts of the world. The indications for treatment were broadened during the years and the procedure became a final step for diagnosis and treatment of unexplained infertility. We conclude that IVF/ET is not an empirical treatment anymore and is a relatively safe procedure, although it should be used only when properly indicated. Male infertility and infertility of unexplained origin may be accepted indications for IVF/ET. More research and centralization of treatment in fewer but large units should be established in order to improve success rates and lower the cost per live birth child. Quality control by professional or public associations should be regulated. PMID- 8491333 TI - The prevalence of endometriosis in women with infertile partners. AB - Laparoscopy was performed on a consecutive series of 174 women complaining of infertility. Forty of these women were the partners of oligospermic or azoospermic men. There was no difference in the prevalence of endometriosis between those women whose partners were fertile and those whose partners were infertile. Women with azoospermic partners had a prevalence of endometriosis of 20.7%, and this is likely to reflect the true prevalence of endometriosis in a group of randomly selected normal women. PMID- 8491334 TI - Langerhans cell histiocytosis of the vulva. AB - A case of an 82-year-old woman with an ulcerated vulvar nodule suspected to be malignant is presented. The lesion turned out to be the primary localization of a generalized Langerhans cell histiocytosis. Six cases with a similar presentation have been reported previously and are reviewed. PMID- 8491335 TI - Colon carcinoma during pregnancy: a lethal coincidence. AB - Carcinoma of the colon during pregnancy is rare. A 38-year-old woman with an obstructive adenocarcinoma of the left colon diagnosed at 27 weeks of gestation is described. Three months and 21 months after hemicolectomy a right, subsequently left ovariectomy was performed because of metastatic disease. Three years after initial surgery, which was followed by chemotherapy, the patient died of metastatic disease. Until now 26 cases of colon cancer during pregnancy have been described; none of these patients have survived 5 years. Metastatic spread of colon cancer to the ovaries in pregnant patients is frequently observed (25%). The fetal risk is very small, because placental and fetal involvement in maternal malignancy is rarely observed, even in widespread metastatic disease. PMID- 8491336 TI - Expectant management of preterm prelabour rupture of membranes--the significance of oligohydramnios at presentation. AB - In a retrospective study, the relationship between oligohydramnios (largest amniotic fluid pocket less than 2 x 2 cm) at the time of presentation and the outcome of expectant management of patients with preterm (< 35 weeks) prelabour rupture of membranes (PROM) was examined in 62 patients admitted with a confirmed diagnosis and in the absence of complications or established labour. There were no differences in the maternal age, incidence of multiparity, or additional complications between patients without (Group 1, n = 24) and with (Group 2, n = 38) oligohydramnios. However in Group 2, 44.7% of the patients developed PROM before 28 weeks and 63.2% were delivered within 48 h of assessment, in contrast to 20.8% (P < 0.05) and 12.5% (P < 0.001), respectively, in Group 1. Group 2 patients had a higher incidence of histological chorioamnionitis (55.3% vs. 29.3%, P < 0.05) and funisitis (44.7% vs. 16.7%, P < 0.02), an earlier mean gestation at delivery (29.1 +/- 2.8 weeks vs. 31.5 +/- 2.0 weeks, P < 0.001) and lower birth weight (1373 +/- 467 g vs. 1856 +/- 496 g, P < 0.001). Our results indicate that oligohydramnios at presentation of preterm PROM is an unfavourable prognostic sign in the expectant management of these pregnancies. PMID- 8491337 TI - The value of Doppler ultrasonography in prolonged pregnancies. AB - One hundred forty-two gravid women at term were followed prospectively by a non stress test, estimation of amniotic fluid volume and Doppler velocimetry of the umbilical and uterine arteries. Adverse perinatal outcome was detected in 12 women (8.5%). Abnormal antepartum tests were detected in 26 women (17%). Seven women had an abnormally elevated resistance index (RI) in the umbilical artery; but only two had an abnormal outcome. Seven women had an abnormally elevated RI in the uterine artery, but only two had abnormal outcome. Three out of 11 women with oligohydramnion had abnormal perinatal outcome. Only one out of seven women with an abnormal non-stress test had abnormal perinatal outcome. In six women, more than one antepartum test was abnormal. The various surveillance methods demonstrated a low sensitivity (the highest was obtained by estimating amniotic fluid volume: 25%) and a low positive predictive value (the highest obtained by measuring the resistance index in either the umbilical or the uterine arteries: 28.6%). By considering any abnormal test as a positive test result for a given patient, a substantial improvement in sensitivity (66.7%) and positive predictive value (33.3%) are obtained. Doppler velocimetry adds very little in itself to the follow-up of patients with post-term gestations. However, when combined with additional antepartum tests, it may increase our ability to predict the compromised fetus in this condition. PMID- 8491338 TI - Per-urethral transvesical first-trimester amniocentesis. AB - Early amniocentesis (before 13 weeks' gestation) using a per-urethral transvesical route is studied. Eight samples were obtained in eight patients scheduled for elective termination of pregnancy. The volume of amniotic fluid averaged 12.5 +/- 7.8 ml. Culture was successful in all samples. In one case, culture was achieved with only 2 ml of amniotic fluid. The amniotic fluid can be easily obtained via the per-urethral transvesical route. We conclude that early per-urethral amniocentesis before 13 weeks amenorrhea may be an alternative to the transabdominal route. A clinical trial should be carried out in order to evaluate both techniques. PMID- 8491339 TI - [Diagnostic value and safety of dobutamine echocardiography in the diagnosis of coronary disease]. AB - To assess the safety and diagnostic value of dobutamine stress-echocardiography (DSE), we studied 109 patients with ischemic heart disease: 78 patients with recent myocardial infarction, 31 patients with chest pain (14 patients without and 17 patients with previous myocardial infarction). Echocardiograms were recorded during dobutamine infusion in 5-minute stages to a maximum dose of 40 mcg/kg/min. The test was considered positive when dobutamine infusion induced a new wall motion abnormality. In 95 pts with recent or previous myocardial infarction new asynergies were classified as being within the infarct zone or outside the infarct zone based on the relation with vascular zones at coronary angiography. All patients underwent exercise stress test (EST) according to the Bruce protocol, and coronary angiography within one week from the test: significant coronary artery disease was defined as > or = 50% diameter stenosis for left main artery and > or = 70% for the other vessels. Five patients (4.6%) had ventricular arrhythmias and 3 patients (2.7%) had systolic blood pressure increase > or = 200 mm Hg in the first stage of DSE, without new wall motion abnormalities, and were excluded from diagnostic value analysis. DSE had a sensitivity of 86% vs 56% of EST (p < 0.001); both had specificity of 94% and positive prognostic value of 98%; diagnostic accuracy of DSE was 87% vs 62% of EST (p < 0.001); negative predictive value was not statistically different. Sensitivity of DSE in single vessel disease (78%) was significantly lower (p < 0.05) than sensitivity in multivessel disease (95%). Sensitivity of DSE in detecting multivessel disease in patients with myocardial infarction was 80% vs 55% of EST (p < 0.05); specificity 96% vs 63% (p < 0.001); diagnostic accuracy 90% vs 60% (p < 0.001); positive predictive value 93% vs 48% (p < 0.001); negative predictive value 89% vs 70% (p < 0.05). At the ischemic threshold, EST caused the achievement of higher heart rate and rate-pressure product; in patients with single vessel disease heart rate was higher than in multivessel disease (141 +/- 19 vs 117 +/- 21, p < 0.001). No differences were detected during DSE in heart rate, blood pressure, rate-pressure product; the dose of dobutamine infused at the ischemic threshold in patients with multivessel disease was significantly lower than in those with single vessel disease (15.2 +/- 5.4 vs 19.4 +/- 6 mcg/kg/min, p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8491341 TI - [Clinical electrophysiology: from pathophysiologic research to non-pharmacologic treatment of supraventricular arrhythmias. The role of surgery and catheter ablation in 1992]. PMID- 8491340 TI - [Effects of vagal tone on Kent bundle conduction in patients with Wolff-Parkinson White syndrome]. AB - BACKGROUND: The influences of the sympathetic tone on the conduction in the Kent bundle have been widely investigated; on the contrary, very little is known about the effects of the vagal tone on such a bypass. Vagal influences on Kent bundle can be adequately investigated only after sympathetic blockade. METHODS: An electrophysiological study was performed in 12 subjects with Wolff-Parkinson White syndrome (7 F and 5 M, age: 30 +/- 17 years) during basal state, after beta blockade (propranolol 0.2 mg/Kg iv) and after atropine (0.04 mg/Kg iv). RESULTS: In no subject were signs of organic heart disease present. The anterograde effective refractory period of the bypass significantly lengthened after propranolol (291 +/- 65 ms vs 313 +/- 52 ms, p < .01), and shortened after atropine (313 +/- 52 ms vs 290 +/- 46 ms, p < .01). This parameter showed no significant differences in the basal state nor after complete autonomic blockade. The longest pacing atrial cycle length for a second degree atrio-ventricular block in the bypass significantly lengthened after propranolol (322 +/- 55 ms vs 383 +/- 44 ms, p < .01) and shortened after atropine, even if the variation was not statistically significant (383 +/- 44 ms vs 368 +/- 39 ms, p: NS); such a parameter was significantly more prolonged after complete autonomic blockade than in the basal state (p < .05). The retrograde conduction in the bypass showed a similar behaviour: the retrograde effective refractory period and the longest ventricular pacing cycle length for a second degree ventriculo-atrial block significantly lengthened after propranolol (434 +/- 133 ms vs 532 +/- 188 ms, p < .01 and 398 +/- 150 ms vs 492 +/- 179 ms, p < .01, respectively) and shortened after atropine (532 +/- 188 ms vs 464 +/- 157 ms, p < .01, and 492 +/- 179 ms vs 431 +/- 158 ms, p < .05, respectively). These parameters were more prolonged after complete autonomic blockade than in the basal state (p < .05). CONCLUSIONS: These data evidence a vagal influence on the conduction in the resting Kent bundle; the vagal effect appears, however, less marked than the sympathetic one. PMID- 8491342 TI - [Congenital isolated complete atrioventricular block: long-term experience with 38 patients]. AB - BACKGROUND: The management of patients with isolated congenital complete heart block is controversial, and indications for cardiac pacing are not clearly defined. In the present study we report our long-term experience in the management of patients with this disease. METHODS: Thirty-eight consecutive patients aged 2 days to 28 years (mean age 10 years) were studied and followed up for 130 +/- 57 months (range 18 to 274). They underwent an extensive evaluation including history, physical examination, electrocardiography and echocardiography; thirty-seven patients had Holter monitoring and exercise test. Electrophysiologic study was performed in 24 patients. RESULTS: Twenty-two patients were asymptomatic, sixteen had symptoms as syncope or presyncope (7 patients), marked exercise intolerance (1 patient), presyncope and marked exercise intolerance (1 patient), heart failure (1 patient), mild dyspnea on exertion (6 patients). Electrocardiograms showed a narrow QRS in all patients. Holter monitoring showed a marked bradycardia (awake heart rate < or = 55 beats/min in infants, < or = 40 beats/min in children and adults) in 15 patients and junctional pauses of > 3 seconds in 9 of them. The exercise test showed a markedly reduced exercise tolerance in 2 patients and exercise-induced complex ventricular arrhythmias in 3 patients. Echocardiography showed a structurally normal heart and a normal left ventricular function in all patients. The electrophysiologic study always showed a suprahisian site of block. Twenty patients (53%) underwent cardiac pacing at a median age of 14 +/- 10 years and were followed up for 110 +/- 59 months (range 18 to 253) after pacing; prophylactic pacing was performed in 10 patients. Indications for cardiac pacing were: syncope or presyncope (7 patients), presyncope and marked exercise intolerance (1 patient), neonatal heart failure (1 patient), marked exercise intolerance (1 patient), neonatal marked bradycardia (2 patients), marked bradycardia with junctional pauses of > 3 seconds and/or complex ventricular arrhythmias (7 patients), complex ventricular arrhythmias (1 patient). No death occurred during the follow-up. In 9 of 20 patients who had cardiac pacing, indication for this procedure appeared during the follow-up (development of symptoms, marked bradycardia and/or complex ventricular arrhythmias). Complications of pacing were infrequent (9 complications in 7 patients) and mainly occurred in the first years of our experience. At present 12 patients have an atrioventricular sequential pacing and 8 have a rate-responsive ventricular one. All patients who had pacing showed an improvement of exercise tolerance; 11 of them underwent exercise test after pacing which showed a significant increase in exercise duration (from 11.1 +/- 1.9 to 15.3 +/- 1.1 min, p < 0.01). In the 3 patients with complex ventricular arrhythmias we observed their suppression after atrioventricular sequential pacing. At present 35 patients are asymptomatic and 3 have mild dyspnea on exertion. CONCLUSIONS: Our results confirm that patients with isolated congenital complete heart block often have symptoms and/or signs of electric instability without symptoms. Cardiac pacing relieves symptoms and improves working capacity. Although in this study we are not able to draw conclusions on the therapeutic value of prophylactic pacing, our favourable follow-up results suggest that this therapeutic approach may prevent complications. PMID- 8491343 TI - [Juvenile sudden death from spontaneous aortic rupture]. AB - In the time interval 1979-1991, 150 cases of juvenile sudden death (< or = 35 years) were studied. Among these, 9 were due to aortic rupture within the pericardial cavity. Two were mycotic and 7 dissecting aneurysms. The latter, all male, age ranging from 17 to 31 years (mean 24), presented the following risk factors: Marfan syndrome in 2, isthmal coarctation associated with bicuspid aortic valve (BAV) in 3, isolated and normally functioning BAV in 2. Histology of the dissected aortic wall showed an equal severity of degenerative changes consisting of elastic fragmentation, cystic medial necrosis and medionecrosis. By reviewing our anatomical collection of dissecting aneurysm we found a 12% frequency of BAV. Taking into consideration that the frequency in normal population of BAV is near 1%, the association between bicuspid aortic valve and dissecting aneurysm should not be casual (p < 0.001). IN CONCLUSION: a) natural history of BAV entails the risk of spontaneous aortic laceration and sudden death in the youth, either in the isolated form or in association with isthmal coarctation; b) the aortic tunica media in these conditions shows an intrinsic structural weakness very similar to that observed in Marfan syndrome, as to suggest a congenital, most probably genetic defect with phenotype expression not only at valve level, but also within the aortic wall; c) aortic dissection occurs nearly ten times more frequently in patients with BAV than in normal population. PMID- 8491344 TI - [Non-invasive conversion of atrial flutter using an implanted double-chamber pacemaker]. AB - The increasing sophistication of implantable pacemakers for treating both tachycardia and bradycardia has resulted in the ability to use the implanted device for more interventions other than simple pacing. The interruption of tachyarrhythmias has been attempted using special programmers which allow stimulation at different cycle lengths, even very short ones. We describe two cases in which neither antitachycardia device nor special equipment were used to terminate an atrial flutter. Two patients with Sick Sinus syndrome who had received DDD pacemaker, presented with a sustained atrial flutter. Pacers were set in AOO mode at the highest rate programmable (119 and 130 ppm, respectively) obtaining an underdrive atrial pacing (F-F rate was 280 ppm in both cases) which was able to convert the atrial flutter to sinus rhythm. The procedure was performed in the outpatient clinic. Our cases illustrate one of many potential applications of permanent pacemakers in noninvasive settings. We can conclude that when atrial flutter occurs in AAI or DDD pacemaker recipients, underdrive atrial pacing using the implanted pacemaker should always be attempted. PMID- 8491345 TI - [Verapamil poisoning for suicidal purposes. A case report]. AB - We report the case of an 82-year-old woman who developed bradyarrhythmia with A-V dissociation and shock, followed by an acute pancreatitis, after ingestion of 2400 mg of verapamil per os for suicidal purposes. Despite her advanced age, the patient promptly improved by a conventional therapy even though started several hours after ingestion of the drug. PMID- 8491346 TI - [Clinical and instrumental findings in cardiac amyloidosis]. AB - The clinical findings of 2 male patients, aged 58 and 60 years with cardiac amyloidosis are described. Congestive heart failure was present in both. Electrocardiograms were abnormal in both cases. Echocardiographic examination showed increased myocardial echogenicity and ventricular hypertrophy, pericardial effusion and decreased ventricular function. Cardiac catheterization was performed in 1 patient. Rectal biopsies were obtained from both patients; endomyocardial biopsy was executed in only 1 patient; all specimens were positive. Our data demonstrate, in agreement with the literature, that clinical features of cardiac amyloidosis are polymorphous and therefore often unidentified. PMID- 8491347 TI - [Unusual electrocardiographic changes on exercise testing in patients with angina pectoris]. AB - We describe three patients with angina pectoris and uncommon electrocardiographic aspects during exercise test. These cases demonstrate the wide variability of the electrocardiographic changes and symptoms during exercise test and may by considered an example of myocardial response to spasm-related ischemia. PMID- 8491348 TI - [Anomalous origin of the left coronary artery from the pulmonary artery. A rare case diagnosed in adulthood]. AB - Anomalous origin of the left coronary artery from the pulmonary artery (Bland White-Garland syndrome) is a rare but often lethal congenital lesion. Clinical manifestations of this syndrome present, in the large majority of cases, in infancy. The authors describe a case of Bland-White-Garland syndrome diagnosed in adult age. PMID- 8491349 TI - [Results of surgical treatment in supraventricular tachycardias]. AB - From May 1989 to May 1992, 44 patients (mean age 41 years, range 15-66) underwent surgery for supraventricular tachycardias: in 35 patients with atrioventricular reentrant tachycardia or atrial fibrillation associated with accessory pathway and refractory to medical treatment, the epicardial approach was used; in 8 with atrioventricular nodal reentrant tachycardia, a perinodal cryosurgery of the atrioventricular node was used, and in 1 patient with atrial flutter a cryosurgical ablation around the orifice of the coronary sinus and surrounding tissues was performed. All 38 accessory pathways were successfully ablated in 35 patients and no recurrences of delta wave or tachycardia were observed during a mean follow-up of 17 +/- 10 months. Atrial perforation during surgery and pericarditis were the only complications observed. All 8 patients with atrioventricular nodal reentrant tachycardia were successfully treated: in 2 patients dual pathways persisted after surgery but tachycardia was no longer inducible. No recurrences were observed during a mean follow-up of 15 +/- 4 months. Since surgery (15 months), the patient with atrial flutter has been free of recurrent episodes of atrial flutter. In conclusion, surgical treatment of supraventricular tachycardias is highly successful, with no mortality and very low morbidity. Should transcatheter ablation fail, surgery should be the treatment of choice in patients with frequent and symptomatic supraventricular tachycardias. PMID- 8491351 TI - [Cardiovascular pathology: an exigency of sociocultural evolving awaiting recognition and structuring]. PMID- 8491350 TI - [The need for invasive diagnostic investigations (coronaro-ventriculography), interventions using extracorporeal circulation and coronary angioplasty in a defined population of Emilia-Romagna]. AB - Working on a limited and controlled population of 100,000 living in the territory of Imola, in northern Italy, we tried to determine the need for coronary arteriography examinations, CABG interventions and PTCA procedures (similarly to the 1980 Minnesota survey). Indications for diagnosis or treatment were made according to agreement criteria of published data in 1990. In the 3 year time (1989-91) of this survey, indication to coronary arteriography was done in 433 pts. (367 atherosclerotic, 58 valvular and 8 with other etiologies). 57.7% (250/433) of the pts. were treated with CABG or PTCA, and 42.3% (202/433) were treated medically. Of the 367 pts. documented as having coronary ischemia, 54.5% had further invasive therapy: 35.4% CABG and 19% PTCA. For a population of 100,000 annual need has been estimated as follows: 145 catheterization procedures (99% coronary arteriography), 60 extracorporeal circulation procedures, and 24 PTCA interventions. Comparing programming estimates done by the national Health System for the needs of a population group in Northern Italy, it is clear that they are underestimating the real needs by 50%, and such an important underestimation implies important and pressing considerations for the future planning of the health care of this important pathology. PMID- 8491352 TI - Echocardiographic vs hemodynamic monitoring during isometric exercise in patients with coronary artery disease. AB - BACKGROUND: Isometric exercise is able to induce myocardial asynergies in patients with coronary artery disease as demonstrated by noninvasive monitoring performed during stimulation. AIMS OF THE STUDY: In the present study, a combined echocardiographic and hemodynamic monitoring of left ventricular contractility has been conducted in order to verify, with invasive and noninvasive techniques, the ability of isometric exercise in inducing transient myocardial ischemic phenomena. METHODS: The study population was composed of 20 patients with angiographic evidence of significant coronary stenosis (> or = 50%), and 10 subjects with normal coronary angiograms. All 30 subjects admitted to the study underwent an isometric exercise stress during echocardiographic and hemodynamic monitoring of left ventricular contractility. RESULTS: Nine out of 20 patients with coronary disease showed regional asynergy during the test (Group I). The remaining 11 patients showed normal myocardial contractility (Group II). None of the 10 control subjects showed mechanical signs of ischemia during the test. Left ventricular end diastolic pressure significantly increased in both Group I (10 +/ 2 to 24 +/- 4 mmHg) and Group II (12 +/- 3 to 26 +/- 3 mmHg) (p < 0.01) while it remained unchanged in the control group (9 +/- 2 to 13 +/- 2 mmHg; p = NS); dp/dt increase (% basal) was significantly higher in the control group (45 +/- 6%) than in either Group I (25 +/- 3%) or Group II (26 +/- 3%) (p < 0.01). CONCLUSIONS: Isometric exercise was able to induce left ventricular asynergies due to regional myocardial ischemia. Hemodynamic contractility monitoring easily distinguished the control subjects from the patients with coronary disease but was not able to discriminate patients with handgrip-induced regional asynergy. Thus, the echocardiographic technique offers more detailed information about regional myocardial function than do the common hemodynamic contractility indexes. PMID- 8491353 TI - [Myocardial scintigraphy with Tc-99m-MIBI for assessing the extent and severity of coronary disease: a comparison with thallium-201 and equilibrium angiocardioscintigraphy]. AB - BACKGROUND: The aim of this study was to compare in the same population of patients affected by coronary artery disease (CAD), the accuracy in the assessment of CAD extent and severity achieved by myocardial scintigraphy, performed using Tc-99m-MIBI with two different imaging techniques (planar and single photon emission tomography--SPECT) and using TI-201 SPECT and by equilibrium radionuclide angiography (RNV). METHODS: We studied 20 patients (18 men and 2 women, age range 42-74) without prior myocardial infarction, but with effort angina. Seven had one-vessel and 13 multi-vessel disease; coronary artery stenosis was > or = 70% and < 80% in 18 arteries and > or = 80% in 19. After therapy withdrawal, all patients underwent (in different days, within 2 weeks): SPECT exercise TI-201 myocardial scintigraphy (early and redistribution images), planar and SPECT Tc-99m-MIBI myocardial scintigraphy (exercise and rest imaging 24 hours apart) and RNV (baseline and exercise studies). RESULTS: All methods were highly sensitive for the diagnosis of CAD: TI-201 SPECT 95%, Tc-99m-MIBI planar 95%, Tc-99m-MIBI SPECT 100%, RNV 100%. For the recognition of the involvement of more than one territory (multi-vessel disease) myocardial scintigraphy with Tc-99m-MIBI SPECT was the most sensitive (92%, p < 0.05 vs Tc 99m-MIBI planar and p < 0.01 vs RNV) and accurate (75%) method, while regional wall motion analysis with RNV showed the highest specificity (100%, p < 0.02 vs TI-201 SPECT, p < 0.05 vs Tc-99m-MIBI SPECT). For the recognition of the involved vessels Tc-99m-MIBI SPECT had the highest sensitivity (89%, p < 0.02 vs Tc-99m MIBI planar, p < 0.002 vs RNV) and global accuracy (80%), while regional wall motion analysis with RNV had the highest specificity (96%, p < 0.02 vs Tc-99m MIBI planar and SPECT, p < 0.001 vs TI-201 SPECT). The degree of obstruction (< 80% vs > or = 80%) significantly influenced the rate of positive RNV results (7/18 vs 14/19, p < 0.05), but not those of the different myocardial perfusion studies. CONCLUSIONS: Our data show that clear differences among the tested methods are present with respect to the assessment of disease extent and severity. SPECT myocardial scintigraphy with Tc-99m-MIBI appears more accurate than the other methods for assessing the extent of CAD. RNV wall motion analysis shows a very good specificity for the recognition of multi-vessel CAD and for the detection of high grade obstructions. This encourages the efforts for studying, whenever possible, not only myocardial perfusion, but also ventricular function and regional wall motion. To this aim the collection of first-pass radionuclide angiocardiography at the moment of Tc-99m-MIBI injection could be particularly advantageous. PMID- 8491354 TI - [The high-resolution analysis of the P wave recorded via the esophagus: a new diagnostic approach in patients with paroxysmal atrial fibrillation]. AB - BACKGROUND: P-wave signal averaged ECG has recently been proposed in the evaluation of patients with Paroxysmal Atrial Fibrillation (PAF). The aim of this study was to verify the utility of this method in the characterisation of these patients utilizing a transoesophageal signal. METHODS: The study population consisted of two groups of subjects: Group A, 34 consecutive patients (16 males; 57 +/- 9 yrs) with a documented PAF and without any underlying heart disease, and Group B, normal controls (9 males; 44 +/- 6 yrs). A signal-averaged ECG, triggered with the oesophageal P-wave, obtained from an X, Y, Z lead system was recorded in each patient, utilizing the AEROTEL HIPEC 200 system. The three orthogonal averaged ECGs were band-pass filtered (non-recursive filter, 40-250 Hz) and combined into a spatial vector magnitudo. We evaluated the filtered P wave duration (Ad, msec) and the Root Mean Square (RMS) voltages of the last 10, 20, and 30 msec of the P vector magnitudo (RMS 10, 20, 30; mcV). RESULTS: The patients with PAF presented with a significantly longer Ad duration (A 126.6 +/- 12.4 vs B 96.8 +/- 12.5 msec, < 0.001), and lower amplitudes of RMS 10, 20, 30 (RMS 10 A 4.8 +/- vs B 9 +/- 2.7 p < 0.005; RMS 20 A 6.9 +/- 2.3 vs B 15.7 +/- 7.3 p < 0.005; RMS30 A 12.1 +/- 5.1 vs B 25.3 +/- 11.5 p < 0.005). An Ad > or = 100 msec, a value of RMS 10 < or = 6.5, RMS 20 < or = 9 and RMS 30 < or = 12.5 mcV showed high values of sensitivity, specificity and positive predictive value (Ad 85%, 100%, 100%, RMS10 93%, 80%, 90%, RMS20 84%, 90%, 96%, RMS30 72%, 90%, 72%). The combined duration/voltage criteria (Ad +/- 110 msec and RMS10 < or = 6.5 mcV or RMS20 < or = 9 mcV) showed a sensitivity of 80% and 76% with a specificity and positive predictive value of 100%. CONCLUSIONS: The P-wave triggered transoesophageal atrial signal averaged ECG appears able to identify patients with PAF; however, prospective studies must investigate the possible clinical use of these findings. PMID- 8491355 TI - [The epidemiology of cardiovascular malformations. III. The prevalence and follow up of 46,895 live births at the Careggi Maternity Hospital, Florence, in 1975 1984]. AB - BACKGROUND: To evaluate the prevalence of congenital heart disease in a homogeneous population we examined 46,895 liveborns in the period from January 1975 to December 1984 in the Careggi Maternity Hospital in Florence. METHODS: The diagnosis of congenital heart disease was made in 579 newborns within five days from birth. All newborns were examined clinically by two neonatologists and referred to the pediatric cardiologist in case of cardiac abnormalities. An ECG was recorded in each of them, chest x-ray in 87% and echo in those who were born after 1980. The children were followed up until December 1989. Mean follow-up period was 6 years. RESULTS: The annual incidence ranged from 9.5% to 15.7% (average 12.3%). Chromosomic anomalies and extra-cardiac malformations occurred in 102 children (17.6%), respectively in 50 (8.6%) and 52 (9.0%) cases. Ventricular septal defect (VSD) and the patent ductus arteriosus (PDA), isolated or associated, were the most frequently recognized congenital heart diseases. 52 children (9.0%) were lost at follow-up. The initial diagnosis was changed in 11/579 cases. In 187 children (32.3%) there was a spontaneous disappearance of clinical and/or instrumental findings that had suggested the presence of congenital heart disease at birth: in 144 the diagnosis was VSD, and in 43 PDA. The prevalence of VSD was 4.7 per thousand in the period 1975-80 and 8.6 in the period 1981-84. 131 children (22.6%) died, 127 (96.9%) of them in the first year of life. 52 children were operated on and pulmonary valvuloplasty was performed in 5. CONCLUSIONS: The prevalence of congenital heart disease does not change during a long observation period, while the number of VSDs increases. VSD and PDA spontaneously close in a high percentage of cases. The study suggests the usefulness of an intensive care unit for newborns with severe congenital heart disease, especially for those in the first year of life. PMID- 8491356 TI - [Elevated cardiovascular mortality in subjects over 75 with low values of arterial pressure]. AB - PURPOSE: The purpose of this study was to extend the observations from recent studies that have shown an increased mortality in elderly people with low blood pressure. METHODS: In 1982 we enrolled 88 subjects, 30 males, 58 females, aged 75 90 years, divided into 3 groups, according to their blood pressure and matched for sex, serum cholesterol, smoking and body mass index: Group I: 20 people with blood pressure equal or less than 120/75 mmHg; Group II: 46 subjects with blood pressure level ranging from 130/80 to 145/90 mmHg; Group III: 22 patients with hypertension (blood pressure equal or more than 160/95 mmHg). These three groups were followed for 6 years (1983-1988) to evaluate the mortality from cardiovascular diseases. During this period, no antihypertensive drugs were given, nor did any other treatment significantly modify the value of blood pressure. No patient changed starting group. RESULTS: Mortality from cardiovascular diseases was as follows: Group I: 14 deaths (mean age 82 +/- 5, 8 for heart failure, 2 for myocardial infarction, 4 for stroke); Group II: 8 (p < 0.001 versus Group I, mean age 81 +/- 3, 6 for heart failure, 1 for myocardial infarction, 1 for stroke); Group III: 4 (p < 0.001 versus Group I, mean age 80 +/ 2, 1 for heart failure, 1 for myocardial infarction, 1 for stroke and 1 for sudden death). CONCLUSIONS: This study adds further observations indicating an increase of mortality for cardiovascular diseases in subjects over 75 years with low levels of blood pressure, which could be more dangerous than moderately high levels in older people. PMID- 8491357 TI - [Myocardial infarct complicated by cardiogenic shock due to acute mitral insufficiency: the diagnosis of papillary muscle rupture by transesophageal echo]. AB - We describe a case of a man with acute myocardial infarction of the inferior wall complicated by cardiogenic shock due to acute mitral regurgitation. Transesophageal echocardiography showed the rupture of the posteromedial papillary muscle. The examination (otherwise difficult) was facilitated by the mechanical ventilation by means of an endotracheal intubation. PMID- 8491358 TI - [Pulmonary thromboembolism and thrombolytics in pregnancy: a clinical case report and review of the literature]. PMID- 8491359 TI - [The remodelling of the heart in heart failure: from thoracic radiography to magnetic resonance]. AB - Congestive heart failure represents the most common medical hospital discharge diagnosis, and can occur in patients with preserved indexes of left ventricular systolic function, even in absence of patent coronary or valvular heart disease. The present review examines the role of imaging techniques in the diagnosis and follow-up of these patients. Imaging of the heart has undergone dramatic advances with the development and refinement of new imaging modalities such as echocardiography, computed tomography, magnetic resonance and radionuclide emission tomography. The role of "low-tech" modalities such as chest roentgenogram is discussed. The possibilities offered by ultrasounds or magnetic resonance in tissue characterization are then compared with the actual capability of cardiac imaging in detecting myocardial tissue alterations (oedema, ischemia, myocarditis, etc.) and/or degeneration (fatty degeneration, fibrosis, amyloidosis, etc.). Finally, the potential use in modern clinical medicine of magnetic resonance spectroscopy and positron emission tomography to study myocardial metabolism and cellular function are discussed. PMID- 8491360 TI - [Contractility and left ventricular filling in heart failure: an echocardiographic evaluation]. AB - In this paper we analyze the possibility of investigating the various modalities of pump function alteration by the echocardiographic technique through examination of the different parts of the cardiac cycle. While M-Mode and 2D echocardiography make a precise assessment of the systolic function parameters possible, with the Echo-Doppler technique we can study diastolic function and obtain information about many hemodynamic parameters. "Strain dependent" and "strain independent" diastolic function are studied almost exclusively with the Echo-Doppler technique: the diagnosis of restrictive cardiomyopathy can be established without invasive procedures such as cardiac catheterization. We suggest that, in most heart diseases with cardiac failure, diastolic and systolic dysfunction coexist: in mitral and aortic regurgitation, echocardiography can give precise information on the presence of ventricular dysfunction, even in the presence of very few or no symptoms, which helps the cardiologist make an early surgical or non surgical decision when dealing with such valve pathologies. PMID- 8491361 TI - [The severity of heart failure: from the anamnesis to the measurement of functional capacity]. AB - The evaluation of heart failure severity is discussed in this paper, and the methods are subdivided into subjective or objective domains. In the former, symptoms evaluation, functional classifications (such as NYHA, Canadian Cardiovascular Society and Specific Activity Scale) are found, while exercise tolerance level is the main method of evaluation in the objective domain. Cardiopulmonary exercise test parameters and their relationships with the effort limiting symptoms are discussed, suggesting their usefulness in individualizing non pharmacological treatment in chronic heart failure patients. PMID- 8491362 TI - [Therapeutic washout in the exercise test?]. PMID- 8491363 TI - [Monitoring pregnant patients from risk countries with sickle cell disease and thalassemia. Clinical aspects, screening and prenatal diagnosis]. AB - At the present time, about 3.5 million people from Turkey, Greece, Italy, the Middle East, Africa and Asia are living in Germany. They are potential carriers of beta-thalassaemia and haemoglobinopathies such as sickle cell disease. These diseases are new for most of us and represent a challenge to physicians, taking care of these patients. Not only do we have to learn about the clinical problems of homozygous patients and how to handle them, we also have to become acquainted with the problems related to the heterozygous carrier stage. The large number of asymptomatic pregnant carriers of beta-globin anomalies is a particular challenge for obstetricians. They need to identify carriers through haemoglobin electrophoresis screening, inform the carrier about the meaning of being a carrier, screen the woman's partner, refer for genetic counselling and suggest and explain prenatal diagnosis in case the partner is also a carrier. There is as yet no cure for thalassaemia and sickle cell disease, except for bone marrow transplantation in a few selected cases. Therefore, prenatal diagnosis presents a valuable method of preventing severe chronic diseases. Screening does not only allow genetic counselling, the information gained has also clinical implications for carriers of beta-thalassaemia. In this paper a summary is given of the pathophysiological and clinical features of thalassaemia and sickle cell disease and molecular biology methods to diagnose thalassaemias and sickle cell disease are discussed. In addition, a screening programme for pregnant women from countries at risk is suggested to enable physicians to give optimal care and initiate prenatal diagnosis. PMID- 8491364 TI - [New oncologic therapeutic approaches with hematopoietic growth factors]. AB - The haematopoietic growth factors interleukin-3 (IL-3), erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF, Neupogen) and granulocyte macrophage colony-stimulating factor (GM-CSF) are highly effective endogenous regulators of blood cell proliferation and differentiation. The results of initial clinical studies with these substances show a stimulation of haematopoiesis for numerous dysfunctions of the bone marrow, whereby the therapy of cytostatic-induced myelosuppression is of particular significance for the gynaecologist, specializing in oncology. After further experience with the individual substances, future development in this field will probably focus on the combined use of these growth factors, to stimulate all early developmental stages of haematopoiesis in the bone marrow and--in view of the line-specific effect--to achieve an effect on several lines of differentiation. Of the cytokines quoted, G-CSF (Neupogen) is so far the only growth factor, which is available for oncological indications. The approval of GM-CSF, IL-3 and EPO for oncological indications is pending. If the currently available results are confirmed by further clinical studies, it will be possible--over and above the improvement of cytostatic tolerance--to raise the current cytostatic doses limited by myelodepression, and to analyse, whether better oncological results can be achieved by more intensive chemotherapy, shorter application intervals, or by using previously impossible cytostatic combinations. The employment of haematopoietic growth factors could, in this way, lead to new oncological therapy concepts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491365 TI - [15 years vaginal delivery in post-cesarean status]. AB - In a retrospective study covering a period of 15 years (1976-1991), we investigated 673 births after previous caesarean section compared to a matched pair group. During the observation period, an increase of vaginal delivery after previous caesarean section occurred. This decrease in resection rate (first five years period: 59%, 60% in the period of 1981-1985 and 42% within the last five years) could be achieved mainly in births after only one previous caesarean section. In patients with more than one previous caesarean section, the resection rate remained almost stable at 95%. The rate of complication was low in our study group, especially, if compared to studies in the USA. Three uterine ruptures with one maternal death occurred during the entire observation period. No correlation of the complication rate with an increase of vaginal delivery was observed. The more conservative obstetrical management had no negative impact on foetal outcome. PMID- 8491366 TI - [Hemoglobin--an obstetric risk factor]. AB - The relationship between haemoglobin values (14th to 30th week of gestation), pregnancy outcome and perinatal morbidity was investigated in a prospective study. Subsequently, haemoglobin values, blood pressure, proteinuria and perinatal risk factors, together with the foetal cardiotocogram were abstracted from the obstetrician's records. Preterm birth (25%), intrauterine growth retardation (7.6%) gestational hypertension (31.5%) and low birth weight babies (10.3%) were seen significantly more often in women with haemoglobin > or = 13 g/dl in the 2nd trimester (14-30 wk). We observed a high perinatal morbidity from RDS (9.3%) and newborn hyperviscosity (23.9%) in women with a high haemoglobin level. These results were in agreement with the hypothesis, that a higher blood viscosity or a lack of haemodilution are risk factors for poor placental perfusion. PMID- 8491367 TI - [Analysis of perinatal mortality as an obstetric quality factor exemplified by the Hessian Perinatal Study 1981-1989]. AB - In a retrospective study, the perinatal mortality between 1981 and 1989 in Hesse is analysed with the help of the Hessische Perinatalerhebung (Hessian Perinatal Study, HEPE). The frequencies of antepartum, subpartum, and neonatal death (< or = 7th day) are studied in relation to the birthweight of the newborn. For the first time in 1982, the neonatal mortality was below the rate of the stillborn foetuses. The subpartum mortality is remarkably low since 1985 (< 0.3%). The number of stillbirths with antepartum death is unchanged since 1985 and their relative amount increases as the neonatal mortality decreases further. The improvement in neonatal mortality concerns particularly the very low birthweight infants below 1500 g, and especially those below 1000 g. The survival of the born alive fetuses below 1000 g birthweight show an additional improvement, when they are born in a perinatal centre. The death of the stillborn babies occurs antepartum in 90% and concerns approx. 80% of fetuses with more than 1499 g and in nearly 50% fetuses weighing more than 2499 g. Lethal malformations are of no importance in antepartum mortality. An improvement in antepartum foetal losses seems to be possible in Hesse and could lead to a decrease in perinatal mortality to below 5% in the years to come. PMID- 8491368 TI - [Value of endoscopic ovarian surgery--critical analysis of 626 pelviscopically operated ovarian cysts at the Kiel University Gynecologic Clinic 1990-1991]. AB - During 1990-1991, 626 cystic ovarian tumours measuring > 3 cm diameter were treated endoscopically at the Department of Obstetrics and Gynaecology at the University of Kiel. In 97 patients, either ovariectomy or adnexectomy, and in 529 cases, an ovarian cyst enucleation was performed. In every case, we considered clinical laboratory, pre-examinations as well as a vaginal ultrasound examination to be of extreme importance for our decision. In 1990, we changed 18 times from pelviscopy to laparotomy and in 1991 7 times under the visual impression of an ovarian malignant tumour. The diagnosis was verified 8 times in 1990 and 3 times in 1991. 10 times in 1990 and 4 times in 1991, the patients were laparotomised with benign ovarian tumours, whose form and motility did not indicate laparotomy at the beginning. No case of ovarian cancer was endoscopically biopsied in 1990 1991. Details on the treatment of patients, their brief hospitalisation period and quick reintegration into family and professional life speak for the applied operation technique. PMID- 8491369 TI - [Pelviscopic surgery without pneumoperitoneum? A new method and its effects on anesthesia]. AB - New developments in the field of pelviscopic surgery enable us to perform more extensive, time-consuming and difficult operations. Prolonging the increased intraabdominal pressure carries the risk of dangerous complications, especially in high-risk patients. We introduce a new technique to perform prolonged pelviscopic operations without or with only slightly increased intraabdominal pressure. The abdominal wall is suspended from a fixation frame. Negative effects on anaesthesia caused by prolonged increased intraabdominal pressure can be compensated. Many different pelviscopic operations can be performed using this simple and inexpensive technique, particularly in surgical procedures of the adnexae. This new technique is advantageous especially in high-risk patients, who can no longer be excluded from extensive pelviscopic surgery. PMID- 8491370 TI - [Endoscopically assisted construction of a neovagina--surgical technique and experience]. AB - The specific disadvantage of the Vecchietti technique for construction of a vagina in cases of vaginal agenesis is the need for laparotomy. We describe an endoscopically assisted construction of a vagina by a variation of this method and report on the first five cases operated on without any complications and with good functional results. PMID- 8491371 TI - [Surgical therapy of recurrent stress incontinence]. AB - We reviewed 245 patients, who underwent surgical treatment of stress urinary incontinence between 1982 and 1989. All patients underwent clinical and urodynamic assessment before and an average of 23 months after surgery (range 12 28). 159 patients had not undergone a previous incontinence operation and 86 one or more previous procedures. 42 patients with recurrent stress incontinence underwent a Burch colposuspension, 20 an anterior colporrhaphy and colpoperineoplasty, and 24 a Stamey endoscopic bladder neck suspension. All operations were successful, more frequently in patients undergoing the first surgical attempt at correction of incontinence than in those undergoing surgery for recurrent incontinence (Burch colposuspension 88% vs 69%; anterior and posterior repair 62% vs 20%; Stamey bladder neck suspension 80% vs 52%). In patients with severe stress incontinence both the Burch and Stamey procedures yielded significantly better results than anterior and posterior repair (73% and 66% vs 37%). The urethral closure pressure at rest was unchanged in patients continent after surgery, but significantly reduced in the surgical failures. Stress profile values differed significantly between patients continent after surgery and surgical failures. Also, the vesicourethral junction was elevated further in the continent than in the incontinent women. PMID- 8491372 TI - [Prolongation of a primary twin pregnancy to the 31st week of pregnancy by surgical extraction of the 1st twin in the 17th week of pregnancy for umbilical cord prolapse]. AB - A 24-year-old woman with a twin pregnancy had a premature rupture of membranes (PROM) of the first foetus in the 16th gestational week (gw). After 9 days the umbilical cord prolapsed. In the 17th gw the foetus was extracted by vaginal hysterotomy, because of an inferior anterior wall placenta. The patient remained hospitalised receiving tocolysis, lung maturation induction and prophylactic antibiosis. The pregnancy could be prolonged for 109 days after PROM and 99 days after the extraction of the first twin. The second child was born in the 31st gw by Caesarean section, following uncontrollable labour. PMID- 8491373 TI - [Differential diagnostic and therapeutic considerations of nipple adenoma]. AB - Adenoma of the nipple is a rare benign tumour of the nipple ducts. Clinically, it simulates the Paget's disease. Histologically, papillary adenocarcinoma and intraductal papillary carcinoma must be differentiated in order to avoid excessive or inadequate therapy. Two cases are discussed. PMID- 8491374 TI - [66th Meeting of the Bavarian Society of Obstetrics and Gynecology, 28 to 30 May 1992 in Bayreuth]. PMID- 8491375 TI - Cell interactions and gene interactions in peripheral neurogenesis. PMID- 8491376 TI - LYAR, a novel nucleolar protein with zinc finger DNA-binding motifs, is involved in cell growth regulation. AB - A cDNA encoding a novel zinc finger protein has been isolated from a mouse T-cell leukemia line on the basis of its expression of a Ly-1 epitope in a lambda gt11 library. The putative gene was mapped on mouse chromosome 1, closely linked to Idh-1, but not linked to the Ly-1 (CD5) gene. The cDNA is therefore named Ly-1 antibody reactive clone (LYAR). The putative polypeptide encoded by the cDNA consists of 388 amino acids with a zinc finger motif and three copies of nuclear localization signals. Antibodies raised against a LYAR fusion protein reacted with a protein of 45 kD on Western blots and by immunoprecipitation. Immunolocalization indicated that LYAR was present predominantly in the nucleoli. The LYAR mRNA was not detected in brain, thymus, bone marrow, liver, heart, and muscle. Low levels of LYAR mRNA were detected in kidney and spleen. However, the LYAR gene was expressed at very high levels in immature spermatocytes in testis. The LYAR mRNA is present at high levels in early embryos and preferentially in fetal liver and fetal thymus. A number of B- and T-cell leukemic lines expressed LYAR at high levels, although it was not detectable in bone marrow and thymus. During radiation-induced T-cell leukemogenesis, high levels of LYAR were expressed in preleukemic thymocytes and in acute T leukemia cells. Fibroblast cells overexpressing the LYAR cDNA from a retrovirus vector, though not phenotypically transformed in vitro, had increased ability to form tumors in nu/nu mice. Therefore, LYAR may function as a novel nucleolar oncoprotein to regulate cell growth. PMID- 8491377 TI - Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. AB - Early B-cell factor (EBF) was identified previously as a tissue-specific and differentiation stage-specific DNA-binding protein that participates in the regulation of the pre-B and B lymphocyte-specific mb-1 gene. Partial amino acid sequences obtained from purified EBF were used to isolate cDNA clones, which by multiple criteria encode EBF. The recombinant polypeptide formed sequence specific complexes with the EBF-binding site in the mb-1 promoter. The cDNA hybridized to multiple transcripts in pre-B and B-cell lines, but transcripts were not detected at significant levels in plasmacytoma, T-cell, and nonlymphoid cell lines. Expression of recombinant EBF in transfected nonlymphoid cells strongly activated transcription from reporter plasmids containing functional EBF binding sites. Analysis of DNA binding by deletion mutants of EBF identified an amino-terminal cysteine-rich DNA-binding domain lacking obvious sequence similarity to known transcription factors. DNA-binding assays with cotranslated wild-type and truncated forms of EBF indicated that the protein interacts with its site as a homodimer. Deletions delineated a carboxy-terminal dimerization region containing two repeats of 15 amino acids that show similarity with the dimerization domains of basic-helix-loop-helix proteins. Together, these data suggest that EBF represents a novel regulator of B lymphocyte-specific gene expression. PMID- 8491378 TI - Cyclin D1 is a nuclear protein required for cell cycle progression in G1. AB - A cascade of events is triggered upon the addition of growth factor to quiescent mammalian cells, which ultimately restarts proliferation by inducing the transition from G0/G1 to S-phase. We have studied cyclin D1, a putative G1 cyclin, in normal diploid human fibroblasts. Cyclin D1 accumulated and reached a maximum level before S-phase upon the addition of serum to quiescent cells. The protein was localized to the nucleus, and it disappeared from the nucleus as cells proceeded into S-phase. Microinjection of anti-cyclin D1 antibodies or antisense plasmid prevented cells from entering S-phase, and the kinetics of inhibition showed that cyclin D1 is required at a point in the cell cycle earlier than cyclin A. These results demonstrate that cyclin D1 is a critical target of proliferative signals in G1. PMID- 8491379 TI - The Cdk-associated protein Cks1 functions both in G1 and G2 in Saccharomyces cerevisiae. AB - The CKS1 gene of Saccharomyces cerevisiae encodes a small essential protein shown to interact genetically and physically with the Cdc28 protein kinase. To investigate the specific functions of the CKS1 gene product, conditional temperature-sensitive mutant alleles were generated. The mutations were found to impair the ability of cells to undergo both the G1/S-phase and G2/M-phase transitions of the cell cycle, as well as the ability to bud. Mutants were not defective, however, in their ability to activate Cdc28 kinase as assayed in vitro on the substrate histone H1. It is likely, therefore, that Cks1 mediates a more specialized function of the Cdc28 kinase such as its ability to form specific multimeric complexes or to localize properly in cellular compartments. PMID- 8491380 TI - Negative regulation of FAR1 at the Start of the yeast cell cycle. AB - In budding yeast, a switch between the mutually exclusive pathways of cell cycle progression and conjugation is controlled at Start in late G1 phase. Mating pheromones promote conjugation by arresting cells in G1 phase before Start. Pheromone-induced cell cycle arrest requires a functional FAR1 gene. We have found that FAR1 transcription and protein accumulation are regulated independently during the cell cycle. FAR1 RNA and protein are highly expressed in early G1, but decline sharply at Start. Far1 is phosphorylated just before it disappears at Start, suggesting that modification may target Far1 for degradation. Although FAR1 mRNA levels rise again during late S or G2 phase, reaccumulation of Far1 protein to functional levels is restricted until after nuclear division. PMID- 8491381 TI - An ATP-dependent inhibitor of TBP binding to DNA. AB - An activity in yeast nuclear extracts (termed ADI) is described that inhibits the binding of the TATA-binding protein (TBP) to DNA in an ATP-dependent manner. The effect is reversible, ATP specific, rapid, and is not promoter specific. ADI is specific for TBP because three other protein-DNA complexes are not affected by ADI. The action of ADI is blocked by association of TFIIA with the TBP-DNA complex. ADI activity at the adenovirus major late promoter requires a segment of DNA upstream from the TATA sequence, suggesting that ADI recognizes aspects of both TBP and DNA. The evolutionarily conserved carboxy-terminal domain of TBP is sufficient for ADI recognition, and amino acids in the basic region of TBP are required for ADI action. ADI can repress transcription in vitro in an ATP dependent manner. In the presence of ADI, both TFIIA and TBP are required to commit a template to transcription. A model of ADI action is proposed, and possible roles of ADI in the regulation of the transcription complex assembly are discussed. PMID- 8491382 TI - GAL4 disrupts a repressing nucleosome during activation of GAL1 transcription in vivo. AB - Photofootprinting in vivo of GAL1 reveals an activation-dependent pattern between the UASG and the TATA box, in a sequence not required for transcriptional activation by GAL4. The pattern results from a nucleosome whose position depends on sequences within the UASG. In the wild-type gene, activation by GAL4 and derivatives disrupts this nucleosome. This activity is independent of interactions with DNA-bound core transcription factors and is proportional to the strength of the activator. Presence of the nucleosome correlates with low basal transcription levels under various conditions, suggesting a role in limiting basal expression. We propose a role for the GAL4 activation domain in displacing a nucleosome and suggest that this is part of the mechanism by which GAL4 activates transcription in vivo. PMID- 8491383 TI - Oxytricha telomere-binding protein: separable DNA-binding and dimerization domains of the alpha-subunit. AB - A telomere-binding protein heterodimer of 56-kD (alpha) and 41-kD (beta) subunits binds to the single-stranded (T4G4)2 terminus of each Oxytricha nova macronuclear DNA molecule. The alpha-subunit by itself binds to telomeric DNA. The beta subunit alone does not bind to DNA specifically but interacts with the alpha subunit to form a very stable ternary complex. We show that the formation of alpha-beta-DNA ternary complex is extremely cooperative. Furthermore, the binary complex (alpha-DNA) has a dissociation half-life of much less than 1 min; addition of the beta-subunit increases the half-life to approximately 100 hrs. Libraries of plasmids with random deletions of the open reading frame for the alpha-subunit were introduced into Escherichia coli, and extracts were subsequently checked for both protein expression and DNA-binding activity with or without added beta-subunit. The alpha-subunit was found to contain two structurally separable domains with distinct functions. The amino-terminal two thirds is necessary and sufficient for sequence-specific DNA binding. The carboxy terminal one-third is responsible for alpha/beta-subunit interactions. When expressed separately in E. coli, purified, and mixed together, these two domains reconstitute the activity of the wild-type alpha-subunit (trans-complementation in vitro). The amino-terminal two-thirds of the beta-subunit is necessary and sufficient both for alpha/beta-subunit interactions and for ternary complex formation. We conclude that the alpha-subunit of the telomere-binding protein, like many transcription factors, has separable DNA-binding and protein-protein interaction domains. PMID- 8491384 TI - Multiple extracellular signals govern the production of a morphogenetic protein involved in aerial mycelium formation by Streptomyces coelicolor. AB - The formation of an aerial mycelium by the filamentous bacterium Streptomyces coelicolor is determined in part by a small morphogenetic protein called SapB. A collection of representative bald (bld) mutants, which are blocked in aerial mycelium formation, are all defective in the production of this protein and regain the capacity to undergo morphological differentiation when SapB is supplied exogenously. We now report that most of the bld mutants are rescued for SapB production and aerial mycelium formation when grown near certain other bld mutants. Extracellular complementation experiments of this kind indicate that morphological differentiation is governed by a hierarchical cascade of at least four kinds of intercellular signals. At least one such signal is present in conditioned medium. It is resistant to boiling and protease treatment, and it remains effective even when diluted up to eightfold in fresh medium. PMID- 8491385 TI - Single gene disorders affecting the gastrointestinal tract. PMID- 8491386 TI - Sulphate reducing bacteria and hydrogen metabolism in the human large intestine. PMID- 8491387 TI - Gall stones and gall bladder motility. PMID- 8491388 TI - Pressure events surrounding oesophageal acid reflux episodes and acid clearance in ambulant healthy volunteers. AB - Previous studies of the mechanisms that precipitate acid reflux episodes and acid clearance have used unphysiological, short term hospital based data. A new 24 hour pH and motility recording system combined with computerised data analysis have been used to study naturally occurring acid reflux episodes in healthy ambulant volunteers. A variety of events that produced recognisable transdiaphragmatic pressure patterns were associated with acid reflux episodes (particularly belching). Peristaltic waves were the predominant contractions leading to oesophageal acid clearance and were the commonest contraction type during reflux episodes. Peristaltic wave parameters (amplitude, velocity, frequency, and percentage proportion) varied during different periods of the 24 hour recording. This study has produced new information about 24 hour oesophageal function and naturally occurring acid reflux which will provide a basis for comparison with patients with gastro-oesophageal reflux disease. PMID- 8491389 TI - Phospholipid composition of human gastric mucosa: a study of endoscopic biopsy specimens. AB - Gastric mucosal phospholipids, and in particular those of the surface layer, play an important part in mucosal barrier function. This study examined whether the phospholipid composition of the full thickness gastric mucosa is changed in peptic ulcer disease and gastritis. The phospholipid composition of gastric mucosa from endoscopic biopsy specimens in 28 subjects (eight healthy controls, 12 patients with duodenal ulcer, and eight with chronic atrophic gastritis) was studied. In addition, the phospholipid composition of gastric mucosa was compared with that of duodenal mucosa in 10 patients with duodenal ulcer. As expected phosphatidylcholine and phosphatidylethanolamine prevailed in all three groups. Lysolecithin was the smallest component in the duodenal ulcer and chronic atrophic gastritis groups. The phosphatidylethanolamine value was higher in duodenal ulcer and lower in chronic atrophic gastritis compared with the control group. In chronic atrophic gastritis there was an appreciable amount of phosphatidylglycerol that was not present in patients with duodenal ulcer or in the control group. There was no significant difference in phospholipid composition between antral and duodenal sites in duodenal ulcer patients. In conclusion, the phospholipid composition of gastric mucosa changes in human gastrointestinal diseases but its relation to cellular functions needs further study. PMID- 8491390 TI - Serological diagnosis of Helicobacter pylori--evaluation of four tests in the presence or absence of non-steroidal anti-inflammatory drugs. AB - The host's humoral immune response to Helicobacter pylori has been used in the diagnosis of active infection with these organisms. Several commercial tests are available but there are few and unconfirmed reports of their efficacy. This study aimed to assess and compare the efficacy of the following H pylori serological tests in patients treated or not treated with non-steroidal anti-inflammatory drugs (NSAID): Pyloriset Latex, Helico-G, Biolab Malakit, and Bio-Rad GAP Test IgG. Venous blood was tested at random in 124 patients, 64 of whom had received NSAID and 60 who had not. H pylori IgG antibodies were detected by latex agglutination (Pyloriset), or by ELISA (the remaining tests). Endoscopic gastric antral biopsy specimens were also obtained for urease activity, culture, and histology. Detection of H pylori by at least two of these was considered as a true positive, and its absence in all biopsy specimens as a true negative. The sensitivity values in the presence (or absence) of NSAID were: Pyloriset Latex, 59 (60)%; Helico-G, 79 (74)%; Biolab Malakit, 85 (81)%; and Bio-Rad GAP Test IgG, 100 (95)%. The respective specificity values were: 50 (71)%, 47 (59)%, 50 (65)%, and 30 (29)%. The Bio-Rad GAP Test IgG has the highest sensitivity and the lowest specificity values regardless of NSAID intake. The sensitivity of the other tests, however, is less than that of the standard biopsy related tests and their specificity is even lower in chronic NSAID users. PMID- 8491391 TI - Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralfate alone. AB - Thirty two patients with Helicobacter pylori positive duodenal ulcers resistant to treatment were randomly assigned to 4 weeks' treatment with sucralphate 4 g/day or colloidal bismuth subcitrate 480 mg/day plus amoxycillin from days 1 to 7 and tinidazole from days 8 to 14. After 4 weeks, patients with unhealed ulcers were crossed over to the other form of treatment for a further 4 week period. Patients with healed ulcers were followed up for 1 year without maintenance therapy with clinical and endoscopic investigations 3, 6, and 12 months after healing. Complete healing rates at 4 weeks were 88% (15 of 17) in the colloidal bismuth subcitrate plus antibiotics group and 40% (six of 15) in the sucralphate group (p < 0.05). After cross over, overall healing rates were 88% (22 of 25) and 47% (eight of 17), respectively (p < 0.05). H pylori eradication occurred in 83% of patients treated with the triple therapy. Cumulative relapse rates at 12 months were 12% (two of 17) in patients in whom H pylori had been eradicated and 100% (10 of 10) in those with persistent infection after short term therapy (p < 0.05). These results show that a colloidal bismuth subcitrate plus antibiotics regimen is highly effective in the short term treatment of resistant duodenal ulcers and that H pylori eradication can change the natural tendency to early recurrence of these ulcers. PMID- 8491392 TI - Laser ablation of upper gastrointestinal vascular ectasias: long term results. AB - Forty one patients with bleeding vascular ectasias of the upper gastrointestinal tract who required blood transfusion were treated with endoscopic Nd:YAG laser photocoagulation and followed for 34 months (median). Four distinct groups of patients were identified. There was a sustained reduction in transfusion requirements after laser treatment in all those with single (nine patients) and multiple (seven patients) angiodysplasia, in 12 of 16 (75%) patients with watermelon stomachs, and in six of nine (66%) patients with hereditary haemorrhagic telangiectasia. Overall, 25 patients (61%) required minimal or no transfusion after treatment and nine (22%) whose bleeding was controlled initially, later developed recurrent bleeding which was controlled with further laser (total 34 of 41, 83%). Surgery succeeded in a further three patients (7%) in whom laser had failed (in one case possibly because of laser induced haemorrhage). Five more cases of possible laser induced haemorrhage resolved with conservative treatment. One patient sustained a treatment related perforation and died: one patient with cirrhosis died of encephalopathy within one month of starting laser treatment. In two patients transfusion requirements were unchanged despite laser. Nd:YAG laser is a safe and effective treatment for most patients with upper gastrointestinal angiodysplasia. PMID- 8491394 TI - Bile salt inhibition of motility in the isolated perfused rabbit terminal ileum. AB - The effects of bile on small bowel motility were studied in isolated, perfused rabbit terminal ileum. It was proposed that bile delivery into the distal ileum would inhibit ileal motor activity, by peptide YY (PYY) release and therefore the effect of luminal bile on motor activity was examined and PYY release measured. Luminal bile and taurocheodeoxycholic acid (10 mmol) inhibited ileal motor activity. Arterial infusion of venous effluents from a bile inhibited ileum suppressed motor activity in a second isolated ileum. This shows the presence of a humoral inhibitor of ileal motor activity. Luminal bile increased venous PYY concentrations (42.5 (8.5) to 502 (46.2) pmol/l; p < 0.01) and increased bile salt values (1.7 (0.36) to 88.6 (5.6) 10 mumol/l/l; p < 0.005). Arterial infusion of taurocheodeoxycholic acid at concentrations found in the venous effluent (100 mumol/l/l) suppressed motility (p < 0.001) but infusion of PYY at concentrations in the venous effluent (500.0 pmol/l) failed to inhibit motility. Furthermore, PYY antagonist, PYX 1, failed to reverse the bile induced inhibition of motility. Luminal bile salts inhibit terminal ileal motility and this is independent of PYY release. By slowing motility, bile salts may participate in their own absorption by the 'ileal pump' and in the 'ileal brake' mechanism. PMID- 8491393 TI - Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N oxide. AB - The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis. PMID- 8491395 TI - Presence of N-acyl and acetoxy derivatives of putrescine and cadaverine in the human gut. AB - N-acyl and acetoxy derivatives of putrescine and cadaverine have been found in the faeces of children and in cultures of isolates of gut bacteria. The evidence was accumulated from two dimensional, thin layer chromatography, field desorption mass spectrometry, and accurate mass measurement of the DANS derivatives of the amines. The acetoxy compounds of putrescine and cadaverine have not previously been reported. PMID- 8491396 TI - Screening for gastric carcinoma in coal miners. AB - This study aimed to determine the prevalence of dyspeptic symptoms and premalignant gastric lesions in coal miners and sex matched population control subjects. Retired coal miners and men from the general population in north Nottinghamshire were sent a dyspepsia questionnaire to fill in, and those with upper gastrointestinal symptoms were invited for gastroscopy and biopsy. A total of 1272 men from the general population and 2099 retired coal miners aged 50-75 years took part in the study. Some 977 of 1272 (76.8%) control subjects and 1715 of 2099 (81.7%) miners replied to the questionnaire. A total of 308 of 977 (31.5%) controls and 620 of 1715 (36.2%) miners were positive for at least one symptom. There was a highly significant difference between the numbers of surface mine and underground workers who reported dyspeptic symptoms (66 of 300 (22%) v 425 of 1083 (32.2%) of p < 0.0001). Histology showed that significantly more miners than controls had acute on chronic gastritis (22 v 11%; p = 0.01) and intestinal metaplasia (23 v 8%; p = < 0.0001). Coal miners may be a suitable group for gastric premalignancy screening using an upper gastrointestinal symptom questionnaire and upper gastrointestinal endoscopy. PMID- 8491397 TI - Increased risk of left sided colon cancer in patients with diverticular disease. AB - Certain similar epidemiological characteristics suggest a common aetiology for colon cancer and diverticulosis of the colon. The hypothesis that patients with diverticulosis are at increased risk of developing colon cancer was tested in a retrospective, population based, cohort study in Sweden. A total of 7159 patients (2478 men and 4681 women) who had been given a hospital discharge diagnosis of diverticulosis or diverticulitis of the colon between 1965 and 1983 were followed up during 1985 by means of record linkage procedures. After excluding the first 2 years of follow up, there was not a significant increase in risk (SIR) overall for colon cancer (SIR = 1.2; 95% confidence intervals (CI) 0.9, 1.6) or for rectal cancer (SIR = 1.1; 95% CI 0.7, 1.7). The observed number of right sided colon cancers was as expected (SIR = 0.9; 95% CI 0.5, 1.5). In contrast, an increased risk of left sided colon cancer was found both overall (SIR = 1.8; 95% CI 1.1, 2.7) and consistently in men and women as well as in different age groups. This risk increased the longer the follow up (p value for trend < 0.001). These results do not support the hypothesis of a common aetiology in diverticular disease and colonic cancer but suggest a causal relationship between diverticular disease and cancer of the left colon. PMID- 8491398 TI - Inter-relationships between inflammatory mediators released from colonic mucosa in ulcerative colitis and their effects on colonic secretion. AB - Metabolites of arachidonic acid have been implicated in the pathophysiology of ulcerative colitis-they can stimulate intestinal secretion, increase mucosal blood flow, and influence smooth muscle activity. The influence on the mucosal transport function of culture medium in which colonic mucosal biopsy specimens had been incubated was investigated using rat stripped distal colonic mucosa in vitro as the assay system. Colonic tissue from patients with colitis and from control subjects was cultured. Medium from inflamed tissue contained more prostaglandin E2 (PGE2) and leukotriene D4 (LTD4) and evoked a greater electrical (secretory) response in rat colonic mucosa than control tissue medium. In inflamed tissue, cyclo-oxygenase inhibition (indomethacin) attenuated PGE2 but increased LTD4 production; conversely lipoxygenase inhibition (ICI 207968) inhibited LTD4 production but enhanced PGE2 output. Each inhibitor alone enhanced the electrical response in the rat colon. Inhibition of both enzymes (indomethacin plus ICI 207968) caused a fall in both PGE2 (82%) and LTD4 (89%) production and in the electrical response (57%). Inflamed tissue treated with a phospholipase A2 inhibitor (mepacrine) produced less PGE2, LTD4, and electrical responses when compared with inflamed tissue, either untreated (91%, 92%, and 79% respectively) or treated with cyclo-oxygenase and lipoxygenase inhibition. Incubation with bradykinin stimulated eicosanoid release and electrical response, while a bradykinin antagonist caused a modest inhibition. Analysis of these observations suggests that a combination of arachidonic acid derivatives accounts for about half the secretory response. Other products of phospholipase A2 activity are probably responsible for much of the remainder, leaving up to 20% the result of types of mediator not determined in this study. PMID- 8491399 TI - Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis. AB - A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis. PMID- 8491400 TI - Pathology of the defunctioned rectum in ulcerative colitis. AB - Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir. PMID- 8491401 TI - Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. AB - The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models. PMID- 8491402 TI - Rectal epithelial cell proliferation patterns as predictors of adenomatous colorectal polyp recurrence. AB - To determine whether proliferative patterns in flat rectal mucosal samples can predict the recurrence of adenomatous colorectal polyps, after polypectomy, biopsy specimens from normal looking rectal mucosa were obtained at endoscopy from 55 patients diagnosed for the first time as having adenomatous colorectal polyps. Epithelial cell proliferation was assessed in biopsy specimens through 3H thymidine autoradiography. After polypectomy, patients were followed for 24 months and underwent complete colonoscopy every 6 months to detect and remove any metachronous lesions. In 40 patients second biopsy specimens were taken during one of the follow up colonoscopies to evaluate the stability of proliferative indices over time. The ratio of labelled (S phase) to total cells (labelling index) for the entire crypt, as well as ratios for each of the five equal compartments into which the crypt had been divided longitudinally, was calculated for each patient. Mean labelling indices for upper crypt compartments 3 and 4 + 5 in the 22 patients in whom polyps recurred were significantly higher (respectively p < 0.05 and p < 0.01) than those of the 33 without recurrence suggesting that an upward shift of the crypt's replicative compartment is associated with polyp recurrence. Labelling indices remained essentially unchanged in those patients who underwent biopsy twice. Reproducible kinetic parameters such as these might be useful in planning follow up of patients with adenomatous polyps after polypectomy. PMID- 8491403 TI - Cephalic phase of colonic pressure response to food. AB - A cephalic phase of colonic pressure response to food was sought in five normal subjects (mean age (22.6) years, 22-24), studied on six separate occasions by recording intraluminal pressures in the unprepared sigmoid colon. Gastric acid secretion was measured simultaneously by continuous aspiration through a nasogastric tube. After a 60 minute basal period, one of five 30 minute food related cephalic stimuli, or a control stimulus was given in random order; records were continued for a further 120 minutes. The cephalic stimuli were: food discussion, sight and smell of food without taste, smell of food without sight or taste, sight of food without smell or taste, and modified sham feeding; the control stimulus was a discussion of neutral topics. Colonic pressures were expressed as study segment activity index (area under curve, mm Hg.min) derived by fully automated computer analysis. Gastric acid output was expressed as mmol/30 min. Food discussion significantly (p < 0.02, Wilcoxon's rank sum test) increased colonic pressure activity compared with control or basal activity. Smell of food without sight or taste also significantly (p < 0.03) increased the colonic pressure activity compared with control and basal periods. Sham feeding and sight and smell of food without taste significantly (p < 0.02 and p < 0.03) increased colonic pressures compared with control but not basal activity. The increase in colonic activity after sight of food without smell or taste was not significantly different from control or basal activity (p = 0.44 and p = 0.34). Food discussion was the strongest colonic stimulus tested. Food discussion and sham feeding significantly (p<0.02) stimulated gastric acid output above control and basal values. Sight and smell of food without taste significantly (p<0.02) increased acid output above basal. Smell of food without sight or taste and sight of food without smell or taste did not significantly (p=0.06, p=0.34) increase acid output. In contrast with the effect on colonic pressures, sham feeding was the best stimulus of acid output. Increased colonic pressure activity after food discussion correlated significantly (r=0.45, p<0.02) with gastric acid output. There was no correlation (r=-0.1, p>0.5) between colonic pressure activity and gastric acid output in the control study. These data show that there is a cephalic phase of the colonic response to food. PMID- 8491404 TI - Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis. AB - Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis. PMID- 8491405 TI - GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis. AB - Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype. PMID- 8491406 TI - Hepatic perfusion changes in patients with liver metastases: comparison with those patients with cirrhosis. AB - Previous studies using dynamic scintigraphy have shown that the measurement of changes in hepatic perfusion may be exploited to detect liver metastases. Similar hepatic haemodynamic changes also occur in cirrhosis, however, thereby reducing the diagnostic power of the technique. The ability of duplex colour Doppler sonography (DCDS) to differentiate between the changes in liver perfusion in patients with cirrhosis and those with hepatic metastases was assessed. Hepatic arterial and portal venous blood flows were measured in 30 control subjects, 20 patients with cirrhosis, and 55 patients with overt liver metastases. The Doppler perfusion index (DPI) (the rate of hepatic arterial to total liver blood flow) and the congestive index (ratio of the cross sectional area of the vessel to time averaged velocity of blood flow in the vessel) of the hepatic artery (HCI) and portal vein (PCI) were calculated. The hepatic arterial blood flow of the cirrhotic and metastatic groups was significantly raised compared with that of controls, and the portal venous blood flow of the former groups were reduced (p < 0.0001). The DPIs of the cirrhotic and metastatic groups were therefore significantly raised compared with those of controls (p < 0.0001). No significant difference was noted in HCI values between the three groups. The PCI values of the cirrhotic group, however, were significantly raised compared with those of controls and patients with metastases (p < 0.0001). The data suggest that DCDS measurement of PCI may be of value in differentiating between the hepatic perfusion changes caused by cirrhosis and those resulting from hepatic metastases, thereby increasing the diagnostic power of this technique. PMID- 8491407 TI - Diffuse vascular ectasia of the antrum, duodenum, and jejunum in a patient with nodular regenerative hyperplasia. Lack of response to portosystemic shunt or gastrectomy. AB - The case is reported of a 70 year old man who presented with severe anaemia because of chronic gastrointestinal blood loss. This loss was ascribed to vascular ectasia resembling the gastric antral vascular ectasia syndrome but extended to include the antrum, the duodenum, the jejunum, and, possibly, the cardiac area. This condition was associated with portal hypertension as a result of nodular regenerative hyperplasia. Consecutive treatments including sucralfate, prostaglandin E2, propranolol, organic nitrates, pentoxyphilline, corticosteroids, endoscopic sclerotherapy, portosystemic shunt, total gastrectomy, proved ineffective. PMID- 8491408 TI - Cap polyposis--an unusual cause of diarrhoea. AB - 'Cap polyposis' is a poorly recognised condition with distinct clinical, sigmoidoscopic, and pathological features that may be confused with other inflammatory conditions of the large intestine including pseudomembranous colitis and idiopathic chronic inflammatory bowel disease. The pathogenesis is unknown but on the basis of the characteristic histological appearances, which are similar to those seen in situations where mucosal prolapse is the underlying mechanism, it has been suggested that the latter may be an important aetiological factor. Two cases are described. Histological features in the first (presence of intramucosal elastin) and clinical features in the second (rectal prolapse) support the above hypothesis. PMID- 8491409 TI - Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle? AB - A 72 year old white man developed acute hepatic impairment and renal failure within 24 hours of starting intravenous amiodarone for paroxysmal ventricular tachycardia. After normal initial investigations, there was a noticeable rise in serum transaminases as well as an increase in clotting times, a decrease in renal function and a thrombocytopenia. These changes returned to normal within seven days of withdrawal of the drug without specific treatment, and the patient was later treated with oral amiodarone without any further evidence of hepatotoxicity. Intravenous amiodarone has been implicated in acute hepatic disease on four previous occasions, but it is suggested that polysorbate 80, an organic surfactant added to the intravenous infusion, is a more likely cause of this complication. Similar reactions have been described with polysorbate 80 in association with the 'E-ferol' syndrome in infants. The occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth. PMID- 8491410 TI - Polymyositis associated with ulcerative colitis. AB - An elderly woman with chronic ulcerative colitis who developed proximal muscle weakness, increased serum creatine phosphokinase activity, and histological and electromyographic abnormalities characteristic of polymyositis is described. Treatment with corticosteroids and 5-acetylsalicylic acid was followed by a remission in bowel symptoms, improvement in muscle power, and reversal of electromyographic changes. An autoimmune link between the two disorders seems likely. PMID- 8491411 TI - Multisystem Langerhans' cell histiocytosis with pancreatic involvement. AB - Langerhans' cell histiocytosis, a rare disorder of unknown cause affecting both children and adults, can affect many different organs and present to a wide range of medical specialties. An infant with fatal multisystem Langerhans' cell histiocytosis in whom the pancreas and the intestine were extensively affected is reported. The direct pancreatic involvement by this disease has not previously been described. PMID- 8491412 TI - Methanogenesis in the human large intestine. PMID- 8491413 TI - Biliary endoprosthesis and common bile duct stones. PMID- 8491414 TI - Assessment of proliferation of squamous, Barrett's, and gastric mucosa in patients with columnar lined Barrett's oesophagus. PMID- 8491415 TI - Strategies for hepatitis B infection. PMID- 8491416 TI - Bleeding varices in the elderly. PMID- 8491417 TI - Antiphospholipid antibodies: involvement of protein cofactors. PMID- 8491418 TI - Immunophenotypic and genotypic characterization of B-cell chronic lymphocytic leukemia patients from northern Italy. AB - BACKGROUND AND METHODS: Immunoglobulin (Ig) gene expression and rearrangements provide information about cell lineage, clonality and differentiation of neoplastic lymphoid cells. We performed flow cytometry and Southern blot analysis in 25 patients with chronic lymphocytic leukemia (CLL) from the Po River delta region (Northern Italy), in order to correlate surface immunological phenotype and heavy and light chain gene rearrangements with clinical stages. RESULTS: In these 25 CLL cases, as in the larger group of 165, k-positive (k+) patients were more frequent than lambda-positive (lambda +) ones by a ratio of 59:41, with a predominance of lambda + in stage II (46:54) and of K+ in stage IV (77:23). However, the survival behavior of lambda + and k+ patients was not statistically different. Ig gene rearrangements were found in all patients in accordance with the immunophenotype. When Ig gene analysis was performed on two different occasions in 7 of the 8 who received chemotherapy, there was an increase in the percentage of the germline band. This variation was inversely related to changes in WBC count. In the treated subject who showed a reduction of both WBC count and the germline, there was rapid disease progression and short survival. CONCLUSIONS: Analysis of Ig gene rearrangements in our CLL patients demonstrated: i) the monoclonality of neoplastic cells; ii) no correlation between rearrangements and clinical stages, and iii) that this analysis may be a useful tool in evaluating biological behavior in selected CLL cases showing a discrepancy between hematological data and clinical response to therapy. PMID- 8491419 TI - Growth and sexual maturation in children with thalassemia major. AB - BACKGROUND AND METHODS. Growth and endocrine disturbances are still important problems for patients with thalassemia major, which is a major health problem in southern part of Turkey. In the present study 71 thalassemia major patients over 3 years of age were evaluated for physical and sexual maturation status. RESULTS AND CONCLUSION. Twenty-three patients (32.4%) were below the third centile for height. Growth retardation was more pronounced in patients 10 years of age and up according to height and weight standard deviation scores (SDS). Delay in bone age SDS was found in almost all patients, and 74.5% of our patients over 12 years of age had not yet entered puberty. These results show that growth and endocrine disturbances have significant negative effects in the quality of life of thalassemic patients. More detailed studies will help to solve these problems. PMID- 8491420 TI - Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients. AB - Blackfan-Diamond anemia (BDA) is a rare hypoproliferative anemia occurring in infancy or in early childhood. Patients who fail on usual doses of steroids did not achieve remission with other pharmacological agents. Claims that other molecules such as cyclosporin A (CSA) or antithymocyte globulin (ATG) are effective require substantiation. We treated four transfusion-dependent, steroid unresponsive BDA patients with ATG and methylprednisolone (MP). Only a transient response was obtained in one case. None of these patients responded to high-dose intravenous immunoglobulins (HDIg) or CSA. PMID- 8491421 TI - Granulocytic sarcoma of the ovary in a nonleukemic patient. AB - We report a case of granulocytic sarcoma of the ovary preceding acute myeloid leukemia by twelve months, with no evidence of any hematological involvement at the time of first diagnosis. The patient was initially treated with surgery and chemotherapy for undifferentiated lymphoma and, although this aggressive protocol resulted in a complete response, granulocytic sarcoma recurred as extramedullary disease, followed by the appearance of acute myeloid leukemia. We discuss the clinical, histopathological and immunohistochemical features of the disease, the differential diagnosis and, in particular, the role of early aggressive treatment on the outcome of the patient. PMID- 8491422 TI - Parenchymal renal involvement in three cases of non-Hodgkin lymphomas: clinical and pathological features. AB - Parenchymal neoplastic invasion of the kidneys is a common postmortem finding in patients who have died from advanced non Hodgkin's lymphomas (NHL). However, it rarely causes major clinical consequences, such as impairment of glomerular and tubular function, acute or rapidly progressive renal failure. Renal involvement is even less frequent as a first manifestation of NHL, the so-called "primary" renal lymphoma. A review of the main clinical, diagnostic and pathological aspects of three cases observed in our division is presented here. PMID- 8491423 TI - Use of tissue expansion in clubfoot surgery. AB - Tissue expansion was used successfully to prepare adequate soft tissue for closure following a difficult clubfoot correction. The gradual expansion was done weekly at the outpatient clinics (average 3-4 months). The procedure proved to be useful in severe cases of clubfoot. PMID- 8491424 TI - Excision of the posterior tibial tendon during clubfoot release. AB - In 50 patients (72 clubfeet), the posterior tibial tendon was excised during complete soft tissue clubfoot release. The end results after an average of 3 years were graded as follows: 55.5% excellent, 29.3% good, 8.3% fair, and 6.9% poor. Heel varus and forefoot adduction were the main causes for recurrence. Heel valgus occurred in one foot. Excision of the posterior tibial tendon is safe, does not lead to overcorrection, and may prevent further scarring created when the tendon is lengthened. PMID- 8491425 TI - Comparison of talonavicular dowel arthrodesis utilizing autogenous bone versus defatted bank bone. AB - A simple dowel arthrodesis of the talonavicular joint in an early stage of destruction can reduce pain and prevent the development of valgus deformity in the rheumatoid hindfoot. Previously, we used autogenous dowels made from the iliac crest. In order to facilitate the operation and to get a better fitting dowel, we tried defatted cancellous allograft dowels from which marrow tissue had been removed. The dowels were prepared from femoral heads in our surgical bone bank. At operation, the dowels were embedded in fresh marrow aspirate from the iliac crest and the arthrodeses were stabilized with a staple. Results were evaluated by clinical examination and radiography. The results of four patients were compared with an earlier study of eight patients using autogenous dowels taken from the iliac crest. With both techniques, the patients were relieved of pain in the talonavicular joint, but some had pain from other hindfoot joints. With autogenous dowels, all eight patients healed with radiographic bony union, but with allogenous dowels, the four patients developed fibrotic nonunion. The results indicate that talonavicular arthrodesis should be made using only autologous dowels. PMID- 8491426 TI - Heel pain syndrome: electrodiagnostic support for nerve entrapment. AB - A local entrapment neuropathy has been proposed as one of the etiologies of heel pain, but it has never been documented by electrodiagnostic studies. Primary symptoms in patients suspected of having a neurologic basis for their heel pain include neuritic medial heel pain and radiation either proximally or distally. On physical examination, all patients in our series had reproduction of their symptomatology with palpation over the proximal aspect of the abductor hallucis and/or the origin of the plantar fascia from the medial tubercle of the calcaneus. Twenty-seven patients (20 women and seven men; average age 49) with these clinical characteristics were examined by electromyography and motor/sensory/mixed nerve conduction studies. Bilateral heel signs and symptoms were present in 11 patients. Ten of the patients had a significant history of back pain with referral to the legs. In 23 of the 38 symptomatic heels, abnormalities were identified in the lateral and/or the medial plantar nerves. The number of abnormal values per heel ranged from one to four, with a mean of 2.1. The most common finding was involvement of the medial nerve (57%). Thirty percent of the heels had isolated findings in the lateral plantar nerve and 13% had abnormalities in both plantar nerves. Two patients had electrophysiologic evidence of active S1 radiculopathy, with ipsilateral evidence of plantar nerve entrapment suggesting a "double crush" syndrome. The results of this study support the presence of abnormalities of plantar nerve function in a selected group of patients with neuritic heel pain. PMID- 8491427 TI - Effect of calcaneal lengthening on relationships among the hindfoot, midfoot, and forefoot. AB - To better understand the bony component of pes planus and the means by which the Evans calcaneal lengthening corrects them, we studied the standing radiographs of seven adult patients who had undergone calcaneal lengthening to treat symptomatic pes planus. Weightbearing AP and lateral views done preoperatively and postoperatively were used for the study. For each set of films, the following parameters were measured: on the lateral view; overall length of the calcaneus, lateral talometatarsal angle, lateral talocalcaneal angle, and the calcaneal pitch angle; and on the dorsoplantar view, the talometatarsal and talocalcaneal angle. In addition, the relative coverage of the talus by the navicular was described by an angular measurement based on the relationship of the center of the talus to the center of the navicular. The average improvements in lateral talocalcaneal angle (a reflection of hindfoot valgus) was 6.4 degrees when the long axis of the calcaneus was used and 6.8 degrees when the inferior surface of the calcaneous was used for the measurement. The lateral talometatarsal angle improved an average 11.3 degrees (from an average of 19.7 degrees to 8.4 degrees). The dorsoplantar talometatarsal angle (a measure of forefoot adduction/abduction) improved 15.8 degrees (preoperative average 26.8 degrees, postoperative average 11 degrees). The calcaneal pitch angle improved an average 10.8 degrees (preoperative average 3.2 degrees, postoperative average 14 degrees). The relationship between the talus and navicular was defined by an angular measurement based on the center of each articular surface before and after correction using this measurement. An average improvement of 26 degrees occurred in the alignment of these two articular surfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491428 TI - Anatomic study of arthroscopic portal sites of the ankle. AB - Numerous anatomic structures are at risk when performing ankle arthroscopy through the more commonly utilized portals. The purpose of this paper was to demonstrate the relative safety of each of the arthroscopic portal and Acufex external ankle distractor pin sites by measuring their proximity to the neurovascular structures surrounding the ankle joint. Six fresh cadaver specimens and 12 fresh-frozen, below-knee amputations were utilized for this study. An Acufex ankle distractor was applied using the standard technique. Anteromedial, anterolateral, anterocentral, posterolateral, and posteromedial portals were placed using an 11-blade scalpel to make 5-mm longitudinal incisions. The joint capsule was penetrated and a 3-mm arthroscope was placed into the ankle joint. The skin surrounding each of the portals was carefully removed and the proximity of any nerves or vessels was measured with respect to the arthroscope. At least one incidence of contact or penetration of a nerve or vessel was noted for each site. The anterocentral portal was at greatest risk for nerve or vessel damage. The anterolateral, anteromedial, and posterolateral portals were the safest areas for portal placement, with no penetration of neurovascular structures in any case. PMID- 8491429 TI - Effect of heel height on forefoot loading. AB - Sixty feet of 30 normal subjects were investigated to determine the effect of changing the heel height on forefoot loading. Subjects walked across footplates barefoot and with rigid polyurethane heels attached to the foot with a tubular bandage. The total load on the forefoot remained unchanged at all of the heel heights, but the distribution of the load changed as the heel was raised. The area of forefoot contact with the footplates decreased and there was a deviation of load toward the medial side of the forefoot with a resultant increase in pressure. These effects could contribute to overload of the distal forefoot and especially of the first ray. PMID- 8491430 TI - Tibiotalar joint dynamics: indications for the syndesmotic screw--a cadaver study. AB - Pronation-external rotation ankle injuries involve varying degrees of disruption of the syndesmotic ligaments. The loss of ligament support and alteration in the stability of the mortise have been postulated to lead to an increase in joint reactive forces and traumatic arthritis. The purpose of this study was to determine the changes in tibiotalar joint dynamics associated with syndesmotic diastasis as a result of the sequential sectioning of the syndesmotic ligaments to simulate a pronation-external rotation injury. Dissections were conducted on 10 fresh-frozen, knee-disarticulated cadaveric specimens which were then axially loaded in an unconstrained manner. Tibiotalar joint forces were measured at each level of sequential sectioning of the syndesmotic ligaments, the interosseous membrane, and finally the deltoid ligament. Complete disruption of the syndesmosis with the medical structures of the ankle intact resulted in an average syndesmotic widening of 0.24 mm and no significant change in the tibiotalar contact area or the peak pressure. However, deltoid ligament strain increases with sectioning of the syndesmosis. With the addition of deltoid ligament sectioning, there was an average syndesmotic diastasis of 0.73 mm, a 39% reduction in the tibiotalar contact area, and a 42% increase in the peak pressure. In a simulated unconstrained cadaveric model of a pronation-external rotation ankle injury that results in complete disruption of the syndesmosis, if rigid anatomic medial and lateral joint fixation is obtained and the deltoid ligament complex is intact, syndesmotic screw fixation is not required to maintain the integrity of the tibiotalar joint. PMID- 8491431 TI - Magnetic resonance imaging and the evaluation of tarsal tunnel syndrome. AB - The bones, soft tissue contents, and boundaries of the tarsal tunnel can be imaged with sufficient detail to show all the major structures within it. Pathological conditions affecting these structures can also be identified. The purpose of this paper was to determine the ability of magnetic resonance imaging to help in the evaluation of tarsal tunnel syndrome. Thirty-three patients with 40 feet were used for this study. All patients presented with complaints of pain along the course of the posterior tibial nerve or its branches and a positive Tinel's sign. Nerve conduction studies were obtained on 29 feet. All feet were evaluated with a magnetic resonance imaging study of the tarsal tunnel. Twenty one feet eventually required surgery. Magnetic resonance imaging revealed an inflammatory or mass lesion in the tarsal tunnel in the majority of cases. The magnetic resonance imaging findings were confirmed at surgery in 19 patients. The information provided by magnetic resonance imaging can enhance surgical planning by indicating the extent of decompression required. PMID- 8491432 TI - Fusion of the metatarsophalangeal joint of the great toe with Herbert screws. PMID- 8491433 TI - Controversies in ankle fractures. PMID- 8491435 TI - What's a foot surgeon to believe? PMID- 8491434 TI - Transverse proximal diaphyseal fracture of the fifth metatarsal: a review of 12 cases. PMID- 8491436 TI - [Hypogonadism and delayed puberty. Indications for androgen treatment in adolescents]. AB - Testosterone and synthetic androgens were once used somewhat uncritically; on account of the undesired side effects that are now known to occur, however, they should be employed very selectively, in particular in the young patient. Although the main indication is primary hypogonadism, they are also employed in the treatment of gonadotropin deficiency and constitutionally delayed growth and development. While, for the treatment of congenital anorchism a therapeutic scheme could be developed which closely approximated the physiological conditions, no generally applicable treatment schemes could be established for other forms of primary hypogonadism. In the case of constitutional retardation of growth and development, treatment is not indicated, for somatic reasons, although severe psychosomatic disturbances may make treatment necessary in many cases. PMID- 8491437 TI - [Andrologic indications for assisted reproduction techniques. When can increased fertilization rates by assisted reproduction be expected?]. AB - Basics: When the cause of a sterile marriage must be assumed to lie with the husband, attempts are often made to resolve the problem by applying the techniques of assisted reproduction, viz insemination and in vitro fertilization (IVF). In such a case, this is the treatment of the wife, who may herself be completely healthy. Major points: In the case of oligoasthenoteratozoospermia (OAT) syndrome, the various techniques available are unable to decisively increase the conception rate. In particular, all IVF working groups are agreed that successes are greatly reduced in the case of inferior sperm quality, as compared with other indications. The "poorer" the original findings, the lower are the fertilization rates. The costs of IVF of about DM 6,000 per cycle mean that, with a success rate of some 8%, the overall cost for each pregnancy is about DM 72,000. This fact tends not to receive sufficient mention in discussions with the married couple. So far, it has not been possible to predict the success rate of an IVF on the basis of an examination of the ejaculate with any degree of accuracy with the aid of the parameters sperm cell density, motility and morphology. Nor do biological tests or an investigation of acrosome function help improve the situation. Even the direct observation of the fertilization of a human ovum, is of questionable value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491438 TI - [Hemorheologic effects of ginkgo biloba extract EGb 761. Dose-dependent effect of EGb 761 on microcirculation and viscoelasticity of blood]. AB - METHOD: In a randomized open clinical trial involving 42 patients with pathological visco-elasticity values, the effect of a single intravenous injection of 50, 100, 150 or 200 mg of the Ginkgo biloba extract EGb 761, commercially available as Tebonin p.i. on the microcirculation of the skin (Doppler flowmetry) and the visco-elasticity of whole blood was investigated. RESULTS: A dose-dependent significant increase in the microcirculation was found. In the case of visco-elasticity, this dose-dependence was less marked. The present study thus confirms the positive effect of EGb 761 on the microcirculation and whole-blood visco-elasticity in patients with pathological visco-elasticity values, already found in earlier studies, and shows it to be dependent on the dose employed. PMID- 8491439 TI - [The feet are always fungus susceptible. Treatment of dermatomycoses in general practice: 1. Indications. Interview by Dr. T. U. Keil]. PMID- 8491440 TI - Digitalis in patients after myocardial infarction. AB - For more than two centuries digitalis has been used in the treatment of cardiac disease. Despite this long clinical experience with the drug, controversy still exists as to its clinical effect and impact on survival, especially in patients after myocardial infarction. In the last decade a number of studies have addressed the problem of assessing the clinical effect of digitalis in patients with sinus rhythm and left ventricular dysfunction. An overall conclusion from these studies seems to indicate that a modest clinical beneficial effect can be expected from the drug. Regarding the effect of digitalis on the mortality in patients after a myocardial infarction controversy still prevails. All studies show an increased mortality in patients using digitalis, but opinions differ as to whether this is due solely to baseline imbalances between the populations or that a harmful effect of digitalis itself exists as well. This question cannot be answered with certainty until the results from a large, randomized study are available. In the meantime digitalis can probably be used as a first line therapy in patients with atrial fibrillation and left ventricular dysfunction. In patients with sinus rhythm and heart failure, however, it is probably wise to reserve digitalis to those that are still symptomatic after diuretics, nitrates and ACE inhibitors have been tried. PMID- 8491441 TI - [Drug interactions with digitalis glycosides]. PMID- 8491442 TI - Transcatheter closure of atrial and ventricular septal defects. AB - The clamshell double umbrella (Bard Clamshell Septal Umbrella, USCI Division, C. R. Bard, Billerica, MA) was developed to allow closure of septal defects, both atrial and ventricular. The device and delivery system and the techniques for implanting the device in atrial and ventricular defects are described in detail. Although fractures of the arms supporting the umbrellas in some patients have lead to modification of the device, the early experience in clinical trails are encouraging. PMID- 8491443 TI - Acute hemodynamic effects of digitalis. AB - The available data suggest that acute administration of digoxin improves rest and exercise hemodynamics in patients in sinus rhythm or in atrial fibrillation who manifest a low cardiac output and increased left ventricular end-diastolic pressure that is due to systolic dysfunction. It appears that these acute beneficial effects are maintained during chronic digoxin therapy. The hemodynamic effects of digoxin in patients with isolated diastolic dysfunction and abnormal hemodynamics remain to be investigated. PMID- 8491444 TI - [Effectiveness of digitalis in patients with chronic heart failure and sinus rhythm. Review of randomized, double-blind and placebo controlled studies]. PMID- 8491445 TI - Anionic polypeptide fraction in bile of patients with and without gallstones. AB - With the demonstration of pronucleating and antinucleating proteins, the role of biliary proteins became of considerable research interest. Anionic polypeptide fraction is the third most abundant biliary protein; it is found in association with biliary lipids, has antinucleating properties for calcium and is found in gallstones. Its levels in various human biles have not been studied as of this writing. In this investigation the concentration of anionic polypeptide fraction in gallbladder bile was measured in 16 subjects without gallstones, 19 subjects with cholesterol stones and 15 subjects with pigment stones in Tel Aviv. Anionic polypeptide fraction concentrations in bile (mean +/- S.D.) were 0.76 +/- 0.09 gm/L in controls and 0.81 +/- 0.25 gm/L (which was not significant) in patients with cholesterol gallstones. They were significantly higher 1.03 +/- 0.23 (p < 0.05) in patients with pigment gallstones. The anionic polypeptide fraction/phospholipid ratio and the anionic polypeptide fraction/total lipid ratio were significantly higher in patients with pigment gallstones (p < 0.005 and 0.05, respectively). The anionic polypeptide fraction lipid ratios were insignificantly elevated in biles of patients with cholesterol stones compared with the ratios in biles of controls. Only the anionic polypeptide fraction/phospholipid ratio was significantly higher in biles of patients with pigment stones compared with those with cholesterol gallstones. The values were similar although higher in a small group of gallstone patients from Marseilles. The role of anionic polypeptide fraction in the pathogenesis of gallstones, particularly pigment gallstones, requires further study. PMID- 8491446 TI - Brachial and femoral artery blood flow in cirrhosis: relationship to kidney dysfunction. AB - Brachial artery and common femoral artery blood flows and cardiac output were measured with duplex-Doppler ultrasonography in 12 normal subjects, 12 patients with compensated cirrhosis and 35 patients with cirrhosis and ascites (8 with functional kidney failure). The aim of this study was to investigate whether arteriolar vasodilation in these vascular territories contributes to hyperdynamic circulation in cirrhosis. Cardiac output was significantly increased and systemic vascular resistance significantly reduced in the three groups of cirrhotic patients. We found no significant differences between normal subjects and compensated cirrhotic patients in brachial artery (55 +/- 7 vs. 57 +/- 7 ml/min) and femoral artery (353 +/- 20 vs. 310 +/- 25 ml/min) blood flow. Nonazotemic cirrhotic patients with ascites showed significantly lower (p < 0.05) brachial artery blood flow (40 +/- 3 ml/min) than healthy subjects and compensated patients. Femoral artery blood flow (327 +/- 25 ml/min), however, was not significantly different. Brachial artery (25 +/- 3 ml/min) and femoral artery (213 +/- 22 ml/min) blood flows were markedly reduced in the patients with kidney failure (p < 0.05 with respect to the other three groups). Glomerular filtration rate correlated directly with brachial (r = 0.74, p = 0.0001) and femoral (r = 0.52, p = 0.03) artery blood flow in the cirrhotic patients. These results indicate that the arteriolar vasodilation causing hyperdynamic circulation in cirrhosis does not take place in the brachial and femoral vascular territories. PMID- 8491447 TI - Renal effects of acute isosorbide-5-mononitrate administration in cirrhosis. AB - The aim of this study was to assess the effects of an oral dose (20 mg) of isosorbide-5-mononitrate on systemic hemodynamics, kidney function, plasma renin activity and plasma aldosterone and atrial natriuretic peptide concentrations in 16 nonazotemic cirrhotic patients. Isosorbide-5-mononitrate significantly reduced cardiopulmonary pressures, cardiac output, peripheral vascular resistance, mean arterial pressure, renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and atrial natriuretic peptide concentration and significantly increased renin and aldosterone values. Cardiopulmonary pressures, atrial natriuretic peptide, cardiac output and mean arterial pressure decreased to a similar extent in patients with (n = 9) and without ascites (n = 7). In patients with ascites we noted marked increases in plasma renin activity (3.7 +/- 1.1 ng/ml/hr to 6.4 +/- 1.8 ng/ml/hr; p = 0.01) and aldosterone level (61.1 +/- 17.5 ng/dl to 108.4 +/- 36.1 ng/dl; p = 0.01). In contrast, in patients without ascites the elevation of plasma renin activity (0.5 +/- 0.16 ng/ml/hr to 0.95 +/- 0.27 ng/ml/hr; p = 0.02) and aldosterone level (5.9 +/- 1.3 ng/dl to 12.3 +/- 3.8 ng/dl; p = 0.02) was mild, and in no case did these parameters increase over the upper normal limit. Isosorbide-5-mononitrate produced a significantly greater reduction of glomerular filtration rate (-21.4% +/- 3.3% vs. -8.9% +/- 4.2%; p = 0.03) and free water clearance (-82.4% +/- 16.1% vs. -34.5% +/- 12.3%; p = 0.03) in patients with ascites than in those without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491448 TI - Biliary abnormalities associated with extrahepatic portal venous obstruction. AB - We prospectively studied 21 consecutive patients with extrahepatic portal venous obstruction for evidence of biliary tract disease. Two patients were first seen with extrahepatic cholestasis; another had recurrent cholangitis. All three patients with clinically manifest biliary disease were adults. Another five patients had icterus on clinical examination. Liver function tests revealed elevated bilirubin levels in 14 patients (66.6%), elevated alkaline phosphatase levels in 17 (80.9%) and elevated serum ALT levels in 8 (38.0%). Endoscopic retrograde cholangiography revealed abnormal findings in 17 patients (80.9%). The changes involved the common bile duct (66.6%) more often than they did the hepatic bile ducts (38.1%). Cholangiographic abnormalities included strictures (52.4%), caliber irregularity (23.8%), segmental upstream dilatation (42.8%), ectasia (9.5%), collateral veins causing extraluminal bile duct impressions (14.3%), displacement of ducts (9.5%), angulation of ducts (4.7%) and pruning of intrahepatic ducts (9.5%). The pathogenesis of such cholangiographic abnormalities is unknown. However, possible factors in such changes include collateral veins bridging the blocked portal vein, causing bile duct impressions; fibrous scarring of porta hepatis, causing angulation of bile duct; and ischemic injury to bile duct, leading to stricture formation and caliber irregularity. Biliary disease is important in the clinical outcome of patients with extrahepatic portal venous obstruction because variceal sclerotherapy has prolonged the life expectancies of such patients. PMID- 8491450 TI - Changes in type IV collagen content in livers of patients with alcoholic liver disease. AB - An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491449 TI - Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin. AB - Technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin is a newly developed analog ligand to asialoglycoprotein receptor, which is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Hepatic functional imaging, which yields estimates of asialoglycoprotein receptor concentration, was performed after intravenous injection of 3 mg technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin. A total of 75 human subjects were studied: 6 controls without liver diseases, 51 patients with chronic liver diseases and 18 patients with acute liver diseases. In chronic liver disease the asialoglycoprotein receptor concentration significantly correlated with the clinical severity based on the criteria of the Liver Cancer Study Group of Japan (rs = -0.890, p = 0.0001). Good correlations between the asialoglycoprotein receptor concentration and conventional liver function tests were also observed. In acute liver disease the asialoglycoprotein receptor concentration correlated well with the normotest (r = 0.796, p = 0.0001), prothrombin time (r = 0.701, p = 0.0002) and total serum bilirubin (r = -0.642, p = 0.0007). We conclude that the parameter, asialoglycoprotein receptor concentration, obtained from the kinetic analysis of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin time-activity data, is a sensitive measure of functioning hepatocyte mass in acute and chronic liver disease. PMID- 8491451 TI - Abnormalities in proximal small bowel motility in patients with cirrhosis. AB - Because altered intestinal motility could be involved in the pathogenesis of small intestine bacterial overgrowth observed in some patients with cirrhosis, we investigated fasting proximal small bowel motility in 16 cirrhotic patients and 8 healthy controls. In addition, the effects of oral tetracycline administration on duodenal motility were investigated in seven cirrhotic patients with evidence of bacterial overgrowth. The mean duration and characteristics of the migrating motor complex were analyzed. Cyclic activity was observed in all healthy controls. It was absent in two cirrhotic patients showing a prolonged phase 2 like pattern. The duration of cycles was significantly longer in the remaining 14 patients with cirrhosis (166 +/- 19 min) compared with controls (81 +/- 14 min; p < 0.02). This difference was caused by a prolonged phase 2 (138 +/- 19 min in patients with cirrhosis vs. 52 +/- 11 min in controls; p < 0.02). Marked changes in the contraction pattern during phase 2 were noted in cirrhotic patients. They were characterized by multiple clusters (frequency, 12 +/- 1/hr; duration, 38 +/- 3 sec) of contractions (frequency, 11 +/- 1 cpm) separated by quiescent periods (duration, 2.4 +/- 0.2 min). This motility profile filled up 58% +/- 8% of the total duration of phase 2, and it was observed in patients with and without bacterial overgrowth. Treatment with tetracycline was followed by only mild modifications, such as a reduction of the fraction of phase 2 occupied by multiple-clustered contractions. In conclusion, an altered proximal small bowel motility has been observed in patients with cirrhosis. These disturbances appear not to be dependent on the presence of bacterial overgrowth. PMID- 8491452 TI - Concordance of iron storage in siblings with genetic hemochromatosis: evidence for a predominantly genetic effect on iron storage. AB - Phenotypic concordance between siblings has been demonstrated in some inherited conditions, and such data provide strong evidence that the severity of disease is affected by genetic factors. We assessed the concordance of liver iron stores between siblings in 22 sibling pairs (15 same-sex pairs and 7 opposite-sex pairs) with genetic hemochromatosis. In this study population a wide range was found in the hepatic iron concentration and the hepatic iron index (32 to 833 mumol/gm dry wt and 1.65 to 14.4, respectively), which could not be accounted for by differing exposure to the environmental factors that influence iron stores. Despite the large variation of hepatic iron concentration within the group, siblings of identical sex had accumulated similar amounts of liver iron. A highly significant correlation for hepatic iron concentration (r = 0.81) and hepatic iron index (r = 0.70) was found between siblings of the same sex. The hepatic iron concentration and the hepatic iron index of one sibling was less than 50% of the other in only three same-sex sibling pairs. In each instance, reasons existed (blood donation, age at diagnosis and human leukocyte antigen nonidentity) for this discordance. In six of the seven opposite-sex pairs, the woman had lower hepatic iron stores than her male sibling, consistent with previous studies on the extent of iron overload in women and its modification by physiological blood loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491453 TI - Futile cycling between 4-methylumbelliferone and its conjugates in perfused rat liver. AB - Futile cycling between 4-methylumbelliferone and its sulfate and glucuronide conjugates was examined in the single-pass perfused rat liver preparation. The steady-state hepatic extraction ratio of 4-methylumbelliferone was found to be high (0.97) at a low input concentration of 0.005 mumol/L (tracer), with a net 4 methylumbelliferyl sulfate/4-methylumbelliferyl glucuronide ratio of about 5:1; at 63 mumol/L the steady-state extraction ratio had remained constant despite a shift from net sulfation to net glucuronidation. At higher input 4 methylumbelliferone concentrations, saturation was evidenced by a decreased steady-state extraction ratio and reduced net sulfation and net glucuronidation. Because 4-methylumbelliferyl sulfate and 4-methylumbelliferyl glucuronide deconjugation would result in an intracellular accumulation of 4 methylumbelliferone, the phenomenon was monitored with a shift in tracer [3H]4 methylumbelliferone metabolism from sulfation to glucuronidation with increased intracellular 4-methylumbelliferone concentration. When 4-methylumbelliferyl sulfate (0 to 890 mumol/L) or 4-methylumbelliferyl glucuronide (0 to 460 mumol/L) was delivered simultaneously with tracer [3H]4-methylumbelliferone to the rat liver, notable desulfation of 4-methylumbelliferyl sulfate (18% to 38% rate in) but little deglucuronidation of 4-methylumbelliferyl glucuronide (1.2% to 2.1% rate in) was observed. With 4-methylumbelliferyl sulfate, 4-methylumbelliferone and 4-methylumbelliferyl glucuronide were readily found as metabolites, whereas with 4-methylumbelliferyl glucuronide, levels of the metabolites, 4 methylumbelliferone and 4-methylumbelliferyl sulfate, were much reduced. 4 Methylumbelliferyl sulfate and not 4-methylumbelliferyl glucuronide shifted tracer [3H]4-methylumbelliferone metabolism from [3H]4-methylumbelliferyl sulfate to [3H]4-methylumbelliferyl glucuronide formation in a concentration-dependent fashion. The steady-state extraction ratio for 4-methylumbelliferyl sulfate (0.1 to 0.3) was comparatively higher than that for 4-methylumbelliferyl glucuronide (0.05), and it was found to increase with concentration, an observation explained by the nonlinear protein binding of 4-methylumbelliferyl sulfate. Biliary excretion rates for 4-methylumbelliferone and 4-methylumbelliferyl sulfate were proportional to their input or net formation rates, regardless of whether 4 methylumbelliferone, 4-methylumbelliferyl glucuronide or 4-methylumbelliferyl sulfate was administered. By contrast, the excretion rate of 4-methylumbelliferyl glucuronide when administered was only 1/25 the excretion of 4-methylumbelliferyl glucuronide formed from 4-methylumbelliferone and 4-methylumbelliferyl sulfate. The extent of choleresis paralleled the excretion patterns of preformed and formed 4-methylumbelliferyl glucuronide; bile flow was normal with 4 methylumbelliferyl glucuronide administration and was markedly enhanced with increased 4-methylumbelliferone or 4-methylumbelliferyl sulfate administration. The data suggest the presence of a transmembrane barrier for entry of 4 methylumbelliferyl glucuronide and not 4-methylumbelliferyl sulfate or 4 methylumbelliferone into hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8491454 TI - Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis. AB - We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change. PMID- 8491455 TI - Hepatitis E. PMID- 8491456 TI - Changes in hepatocyte water volume affect protein synthesis. PMID- 8491457 TI - Mixed chimerism after transplantation: mechanism or marker of specific tolerance? PMID- 8491458 TI - Drug targeting to the liver with bile acids: the "Trojan horse" resurrected? PMID- 8491459 TI - Clarifying a complex case. PMID- 8491460 TI - Patient-centered care: is it too CEO-centered? PMID- 8491461 TI - What's in a name? PMID- 8491462 TI - New waves. Hospitals struggle to meet the challenge of multiculturalism now--and in the next generation. AB - Multiculturalism means different things to different people. For hospital executives, there are a number of major implications inherent in the rapidly expanding diversity of the United States. Beginning on page 23, we look at the ethnic diversity issues hospitals face as employers. A consensus has developed that more minority young people must be encouraged to enter health care administration and clinical care; but there are a variety of obstacles to be overcome. Then, beginning on page 29, we examine the many challenges hospitals struggle with as their patient populations become more and more diverse, and in many cases, change very quickly. Problems in dealing with an array of languages, cultures and backgrounds can put up major barriers to effective patient care. Providers must understand the cultural assumptions that patients bring with them. PMID- 8491463 TI - Contracting gains ground. Annual survey shows 10% rise in use of contract services. AB - Access to specialized expertise and the ability to staff hard-to-fill jobs continue to surpass all other reasons for use of contract management services, according to the annual CEO survey conducted by Hospitals. And most CEOs who use contract services say they're satisfied with them. PMID- 8491464 TI - Patchwork access. Primary care in EDs on the rise. AB - It's been long known that EDs in the nation's largest cities routinely provide non-emergent primary care. But a new study by the AHA and several allied hospital associations has found that a very high proportion of ED visits in each of the four communities studied could have been handled outside the ED. PMID- 8491465 TI - Maturing market. Gaps narrow among emergency physicians' salaries. PMID- 8491466 TI - Computers make 'house calls' to patients. AB - As part of a pilot test, Cambridge, MA-based Harvard Community Health Plan has patients in about 150 households using home computers to receive medical advice and general health information. The system should better educate patients, improve quality of care and lower costs, according to its developers. PMID- 8491467 TI - Data watch. Survey outlines hospital collaboration efforts. PMID- 8491468 TI - What are employee benefits worth--to employees? PMID- 8491469 TI - HCFA works to improve Medicare cost report audits. PMID- 8491470 TI - Managed care safe harbors worrisome, attorneys say. PMID- 8491471 TI - Multiculturalism is the future. PMID- 8491472 TI - Survey highlights the occupational hazards of nursing. PMID- 8491473 TI - "Hospitals" and hospitals: evolving together. PMID- 8491474 TI - The search for the optimal immunohistochemical panel for the diagnosis of malignant mesothelioma. PMID- 8491475 TI - Immunoreactivity of normal and neoplastic human tissue mast cells with macrophage associated antibodies, with special reference to the recently developed monoclonal antibody PG-M1. AB - There is increasing evidence in favor of the hypothesis that human tissue mast cells (MCs) are progeny of hemopoietic stem cells and are closely related to cells of the mononuclear phagocyte system. To test this hypothesis we investigated the immunoreactivity of normal/reactive MCs in 12 lymph node and tumor specimens and neoplastic MCs in 27 tissue samples from patients with various types of mastocytosis (urticaria pigmentosa, n = 13; cutaneous mastocytoma, n = 4; systemic mastocytosis, n = 6; and malignant mastocytosis, n = 4) with a panel of eight antibodies that stain macrophages or immune accessory cells and are reactive on routinely processed (paraffin-embedded, formalin-fixed) tissue. The MCs were stained by three of the macrophage-associated antibodies (namely, KP1 [CD68], Ki-M1P, and PG-M1 [CD68]), but were not stained by three other antibodies (namely, HAM56, MAC387, and LN5) or antibodies detecting immune accessory cells (DAKO-CD35 and anti-S-100 protein). While KP1 stained normal/reactive and neoplastic MCs in all the specimens investigated, Ki-M1P stained neoplastic MCs in nearly all the cases of mastocytosis but did not stain normal/reactive MCs. PG-M1 also failed to stain normal/reactive MCs and stained MCs in only approximately half of the specimens from cases of mastocytosis. Among these were most of the cases of systemic and malignant mastocytosis, but only a minority of the cases of cutaneous mastocytosis and a very few cases of urticaria pigmentosa. To summarize, (1) MCs display immunohistochemical staining properties resembling those of cells of the mononuclear phagocyte system but not those of macrophage derivatives belonging to the immune accessory cell compartment, and (2) PG-M1 and Ki-M1P are unique among the macrophage-associated antibodies investigated in that they do not stain normal/reactive MCs but exhibit preferential reactivity with the more atypical MCs in cases of systemic and malignant mastocytosis. PMID- 8491476 TI - Immature endodermal teratoma of the ovary: embryologic correlations and immunohistochemistry. AB - Two grade 2 ovarian immature, predominantly endodermal teratomas are reported. The teratomas were in stage I and occurred in two girls, 9 and 10 years of age, who were treated with triple chemotherapy. These neoplasms differed from the usual immature ovarian teratoma as they contained no neuroectodermal components and had high alpha-fetoprotein and low human chorionic gonadotropin levels as their serum markers despite the absence of other concomitant germ cell tumors. The epithelia of the teratomas demonstrated exclusively the embryologic development of endoderm, ranging from early endoderm to tissues similar to esophagus, liver, and intestinal structures. All epithelial derivatives were positive for alpha-fetoprotein and alpha 1-antitrypsin. Liver and esophagus expressed fibrinogen, while intestine and esophagus were positive not only for carcinoembryonic antigen and chromogranins but also for thyroglobulin, thus reflecting yet another type of endodermal differentiation into thyroid. Focal human chorionic gonadotropin positivity associated with primitive intestinal and esophageal epithelia may reflect the early embryologic relationships between endoderm and trophoblast. These cases demonstrate that simultaneous alpha fetoprotein and human chorionic gonadotropin secretion may occur in immature teratoma. The mesenchymal component also showed a wide range of differentiation, from primitive mesoblastic cells to differentiated cells, such as hemopoietic foci, smooth muscle, bone, and cartilage. Both the primitive endoderm and the mesenchyme co-expressed vimentin and keratin, reflecting their intimate developmental relationships and possibly supporting the hypothesis of mesenchyme originating from endoderm, as suggested by previous embryologic studies. Since endodermal and mesenchymal areas similar to those described here are found in association with yolk sac tumors and embryonal carcinoma, it is possible that the present cases may represent an endodermal differentiation accomplished by either of these developmentally related germ cell tumors. PMID- 8491477 TI - Necroinflammatory changes in hepatic lobules in primary biliary cirrhosis with less well-defined cholestatic changes. AB - Primary biliary cirrhosis (PBC) is characterized by nonsuppurative inflammation and destruction of interlobular bile ducts. In this study we examined the necroinflammatory changes in hepatic lobules in PBC in the absence of cholestatic changes secondary to bile duct destruction, viral hepatitis types B and C, and progression of histologic stages. Kupffer cell hyperplasia, mononuclear sinusoidal infiltrates, and focal hepatocellular necroses were found frequently in the hepatic lobules. Some cases also showed perivenular zonal necrosis and central to central bridging necrosis. Focal necroses and swollen Kupffer cells were associated with lymphocytes with plump eosinophilic cytoplasm, resembling epithelioid cells. Well-developed and less-defined epithelioid cell granuloma also was occasionally found. The size, number, and distribution of these intralobular necroinflammatory changes varied from case to case and also from lobule to lobule in the same case. beta-2-Microglobulin was expressed on hepatocytes in areas of intralobular necrosis, in association with activated T cells. Laboratory data reflecting necroinflammatory changes in the hepatocytes tended to be elevated in the patients with zonal necroses. It is suggested in this study that necroinflammatory changes in the hepatic lobules are constant and inherent features in PBC and easily recognizable at an earlier histologic stage, and that hepatocytes, in addition to bile duct epithelium, may be targets of the immunologically mediated destruction that characterizes PBC. PMID- 8491478 TI - Ultrastructure of endothelial cell necrosis in classical erythema nodosum. AB - As evidence of vascular involvement in classical erythema nodosum unassociated with Behcet's disease, the occurrence of endothelial cell necrosis based on the development of dark cell degeneration was observed by electron microscopy in the vasculature of the dermis and subcutaneous fat. The incidence of endothelial cell necrosis in all segments of the microcirculatory system was roughly 20% in three of 12 patients. The remaining nine patients showed a very low rate of necrosis, including two patients in whom endothelial cell necrosis was totally absent. The presence of necrotic endothelial cells that are forced out and eliminated by neighboring intact endothelial cells into the vascular lumen is closely associated with thrombus formation in the cutaneous vasculature. The incidence at which endothelial cell necrosis occurs in classical erythema nodosum is not always high; however, it is concluded that endothelial cell necrosis may play a significant role in the pathogenesis of erythema nodosum. PMID- 8491479 TI - Human ehrlichiosis: hematopathology and immunohistologic detection of Ehrlichia chaffeensis. AB - Human ehrlichiosis is a recently described zoonosis caused by a rickettsia that infects leukocytes. Most patients have fever, headache, chills, and myalgias and develop leukopenia, thrombocytopenia, anemia, and elevations in serum hepatic aminotransferases. The cause of the peripheral leukopenia and thrombocytopenia is not known. We studied peripheral blood smears, bone marrow aspirates, and bone marrow biopsy specimens from patients with serologically proven ehrlichiosis to characterize the pathologic changes associated with leukopenia or thrombocytopenia, to detect the presence of immunohistologically demonstrable ehrlichiae, and to establish the infected host target cell(s). Specimens were obtained from 12 patients, and immunohistology for Ehrlichia chaffeensis was performed on tissue sections, aspirated bone marrow, and peripheral blood smears. Mean leukocyte and platelet counts available for nine patients were white blood cell count 3,300/microL (range, 1,100 to 10,300/microL) and platelets 61,000/microL (range, 40,000 to 82,000/microL). Findings included myeloid hyperplasia (eight cases), megakaryocytosis (seven cases), granulomas (eight cases), marrow histiocytosis (one case), myeloid hypoplasia (one case), pancellular hypoplasia (one case), and normocellular marrow (two cases). Morulae of E chaffeensis were detected in four of 10 cases examined by immunohistology. Most ehrlichiae were detected within histiocytes, although morulae were rarely present within lymphocytes. Leukopenia, thrombocytopenia, or pancytopenia apparently most often results from peripheral sequestration or destruction; however, hypoplasia of marrow elements is present occasionally. Immunohistologic demonstration of E chaffeensis offers a direct means for establishing the etiologic diagnosis. These observations show the relatively frequent occurrence of bone marrow granulomas and suggest that infection of cells of the reticuloendothelial system may participate in the pathogenesis of human ehrlichiosis. PMID- 8491480 TI - Steroidogenesis in human adrenocortical carcinoma: biochemical activities, immunohistochemistry, and in situ hybridization of steroidogenic enzymes and histopathologic study in nine cases. AB - To obtain a better understanding of steroid metabolism associated with adrenocortical malignancy we studied steroidogenesis in nine cases of adrenocortical carcinoma (six with Cushing's syndrome, two without clinically significant adrenocortical hormonal abnormalities, and one with primary aldosteronism) by analyzing biochemical enzyme activities (21-hydroxylase and 11 beta-hydroxylase) and by immunohistochemistry and in situ hybridization of steroidogenic enzymes in carcinoma tissues. 21-Hydroxylase activity was markedly low but 11 beta-hydroxylase activity was only moderately decreased compared with normal adrenal activity. Immunohistochemical study of steroidogenic enzymes revealed that six of the nine cases expressed all the enzymes required for cortisol or aldosterone biosynthesis. Immunoreactivity of these enzymes was predominantly observed in small carcinoma cells with compact and/or clear cytoplasm and minimum morphologic nuclear atypia. In those cases with positive steroidogenic enzymes immunohistochemical examination of serial tissue sections revealed that a number of carcinoma cells did not express all the enzymes required for the synthesis of biologically active steroids. This may account for an increased level of precursor steroid secretion associated with adrenocortical malignancy. In situ hybridization of cytochrome 17 alpha-hydroxylase demonstrated that carcinoma cells with positive hybridization signals generally were positive for immunoreactivity, but a discrepancy between mRNA and protein expression was occasionally observed. Although the conclusions derived from our current study are limited by the small number of cases, ineffective corticosteroidogenesis, characteristic of steroid metabolism in human adrenocortical carcinoma, was considered to be due to disorganized expression of steroidogenic enzymes in individual carcinoma cells. PMID- 8491481 TI - Pulmonary changes following extracorporeal membrane oxygenation: autopsy study of 23 cases. AB - Extracorporeal membrane oxygenation (ECMO) has become an established mode of therapy in many centers for potentially fatal neonatal respiratory failure refractory to conventional therapy. We reviewed the findings of 23 autopsies of patients placed on ECMO therapy during the period from 1988 to 1992 at our institution in order to document the pulmonary histopathologic changes and to correlate such changes with the duration of treatment. Interstitial and intra alveolar hemorrhages, as well as hyaline membrane formation, were the most common findings during the first few days of therapy. Reactive epithelial hyperplasia (bronchial and type II pneumocytes), squamous metaplasia, and smooth muscle hyperplasia were observed as early as 2 to 3 days after initiation of ECMO therapy. Interstitial fibrosis was noted only after 7 days of ECMO therapy. In three patients treated for 15, 19, and 21 days there was replacement of the terminal airways and alveoli by tall columnar and mucin-producing epithelium. Alveolar and bronchiolar calcifications were noted in seven of the 23 cases in this series. Pulmonary vascular changes were seen in association with persistent fetal circulation, meconium aspiration, and respiratory distress syndrome. These changes are most likely due to the compounded effect of ECMO and the underlying pulmonary insult. PMID- 8491482 TI - Pigmented pheochromocytomas of the adrenal medulla. AB - Three primary pigmented pheochromocytomas of the adrenal gland are presented. The pigment in all cases proved to be melanin. Two of the pheochromocytomas were sporadic and histologically typical, except for a focal spindle cell configuration in one. It is believed that the morphologic appearance of these tumors represents divergent differentiation from neural crest, expressing typical pheochromocytoma (polygonal cells) and melanocytic features (melanin pigment). PMID- 8491483 TI - An immunohistochemical study of neuronal microtubule-associated proteins in Hirschsprung's disease. AB - Neuronal microtubule-associated proteins (MAPs) are important components of neurons and are believed to regulate neuronal function and development by controlling the assembly of microtubules and the interaction of microtubules with other cytoplasmic organelles. We studied the immunohistochemical localization of MAPs 1, 2, 5, and tau in the intestinal tissues of five patients with Hirschsprung's disease and in five normal controls using monoclonal antibodies. Microtubule-associated proteins 5 and tau proved to be excellent enteric neuronal markers; they were specifically located in the nerve cell bodies and processes of normal intestine as well as in the abnormal hypertrophied nerve fibers of aganglionic colon. Fine fibrillar structures in the neuroplasm were revealed in greater detail than were those obtained from studies with conventional markers, including neuron-specific enolase, S-100 protein, and neurofilament protein. A slight reduction of MAPs 5 and tau immunoreactivity was observed in the aganglionic colon compared with normal colon. Microtubule-associated proteins 1 and 2 were absent from the nerve fibers in both normal and aganglionic colon. This study suggests that immunostaining for MAPs 5 and tau may be superior to other immunohistochemical methods for diagnosing Hirschsprung's disease; however, in view of its limited retrospective nature these findings need to be corroborated by a large prospective evaluation. PMID- 8491484 TI - Giant cystic arachnoid granulations: a rare cause of lytic skull lesions. AB - Arachnoid granulations provide the pathway for drainage of cerebrospinal fluid from the subarachnoid space into the dural venous sinus system. They frequently produce small, well-defined indentations on the inner table of the calvarium that are easily recognized on radiographic studies and gross examination of the skull. We report a series of four giant cystic arachnoid granulations presenting as large "destructive" osteolytic lesions that required surgical exploration. The cysts were filled with cerebrospinal fluid and were delineated by a thin fibrous wall that contained peripheral clusters of arachnoid cells. We discuss the pathologic and radiographic differential diagnosis of osteolytic skull lesions and present a hypothesis regarding the formation of giant cystic arachnoid granulations. PMID- 8491485 TI - Adult intracardiac rhabdomyoma resembling the extracardiac variant. AB - Rhabdomyomas are benign striated muscle neoplasms that may assume a number of characteristic histologic patterns. These lesions may be classified as cardiac or extracardiac on the basis of their location and histology. We present a case of large intracardiac mass with the morphologic features of an extracardiac rhabdomyoma occurring in an adult female. PMID- 8491486 TI - Nucleolar organizer regions in small round cell tumors of childhood. PMID- 8491487 TI - p53: the promising story continues to unfold. PMID- 8491488 TI - Extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) of the head and neck. AB - We report 14 cases of extranodal sinus histiocytosis with massive lymphadenopathy involving a variety of head and neck sites. The patients ranged in age from 3 to 70 years (median, 43 years). Nine cases occurred in women and five occurred in men. The clinical presentation varied depending on the site of occurrence and included nasal obstruction, stridor, proptosis, ptosis, decreased visual acuity, facial pain or tenderness, cranial nerve deficits, mandibular tenderness, and mass lesions. Head and neck sites involved by disease included the nasal cavity, paranasal sinuses, nasopharynx, parotid gland, submandibular gland, larynx, temporal bone, infratemporal fossa, pterygoid fossa, meninges, and orbital region. The majority of patients presented with involvement of more than one site. Nodal involvement was identified in four patients. Special stains for microorganisms were negative. The sinus histiocytosis with massive lymphadenopathy cells demonstrated an immunophenotypic profile supporting derivation from macrophage/histiocytic lineage. Treatment varied and included surgical excision with or without adjuvant therapy (chemotherapy, radiotherapy) or steroids. Several patients required more extensive surgery as a result of extension of their disease to adjacent structures or due to recurrent disease. Twelve patients are alive and either free of disease or have persistent disease. Two patients died, one as a result of complications of disease. PMID- 8491489 TI - Systematization of primary histopathologic and fine-needle aspiration cytologic features and description of unusual histopathologic features of neuroblastic tumors: a report from the Pediatric Oncology Group. AB - On the basis of a detailed review of the primary histopathologic features of 239 cases and the fine-needle aspiration cytologic features of seven cases, a systematized schema of differentiation, progressive maturation and organization, and biologic behavior in neuroblastic tumors (NTs) is presented. The differentiation is of the gangliocytic and schwannian lineages. Maturation occurs in differentiating neuroblasts, leading to the formation of various stages of ganglion cells and Schwann cells. Organization is characterized by nesting pattern, rosette formation, parallel arrangement of neuropil, and alignment of Schwann cells along the neurites. According to this schema the NTs can be arranged in the following order: undifferentiated, poorly differentiated, and differentiating neuroblastoma; nodular, intermixed, and borderline ganglioneuroblastoma; and ganglioneuroma. Formulation of such a schema is helpful in gaining a better understanding of the complex pathologic features and in defining the criteria for various types of NTs. Therefore, the schema also would be helpful in achieving uniformity and reproducibility of the diagnosis of various types of NTs. Previously unreported features related to shape, size, nucleus, and cytoplasm of neuroblasts; secondary changes and patterns; changes in the fibrovascular septa; and other morphologic aspects of NTs and features (such as large tumor cells, karyorrhectic cells in fine-needle aspiration biopsy, tumor giant cells, anaplasia, and nesting pattern of tumor cells that have not been sufficiently emphasized) also are described. The importance of these previously unreported and insufficiently emphasized features relates to the histologic and cytologic diagnosis of NTs. For example, some of the features, such as starry sky appearance and spindle-shaped neuroblasts, may be misleading if seen in a small biopsy specimen. Others, such as tumor giant cells resembling ganglion cells and nesting pattern, will provide clues to the correct diagnosis. Some of the features, such as sclerosing pattern, hyalinization, and dense lymphoplasmacytic infiltration, may be related to the phenomenon of regression exhibited by neuroblastomas. PMID- 8491490 TI - Polymorphic fibro-osseous lesions of bone: an almost site-specific diagnostic problem of the proximal femur. AB - Atypical fibro-osseous lesions, usually in the proximal femur, are a common consultative diagnostic problem. This is due to the fact that they contain a variety of patterns individually reminiscent of fibrous dysplasia, fibroxanthoma (non-ossifying fibroma), myxofibroma, lipoma, cyst, bone infarct, Paget's disease, and, occasionally, chondroma. The variety of patterns in a single lesion precludes a simple designation. A diagnosis based on the predominant pattern would ignore this histologic complexity, which can be predicted by location in the proximal femur and a distinctive radiographic configuration. Personal experience with 95 heterogeneous lesions indicates they are usually incidental findings. They have a broad adult age range, but quite likely have their inception in childhood and slowly alter their appearance over a lifetime. In the majority of instances asymptomatic discovery, lack of distortion of bone outline, and sclerotic borders are indications of stability over many years. Other lesions gradually enlarge, predisposing to pathologic fracture. In parallel with some enchondromas and bone infarcts, a minority of lesions undergo malignant transformation. PMID- 8491491 TI - Stereologic estimation of nucleolar volume in ocular melanoma: a comparative study of size estimators with prognostic impact. AB - The aim of this study was to investigate the relationships between one-, two-, and three-dimensional histomorphometric estimators of nucleolar size in ordinary histologic sections of uveal melanomas from 144 patients. In addition, the prognostic value of the various size parameters was studied. The following estimates were obtained: the mean diameter of the 10 largest nucleoli, the mean nucleolar profile area and associated standard deviation of the nucleolar profile area, the volume-weighted mean nucleolar volume (nucleolar vv), and the macroscopic, largest tumor dimension. All histomorphometric parameters were highly intercorrelated (r > .75). The correlation between the largest tumor dimension and the nucleolar vv was rather poor (r = .35). The efficiency of the sampling scheme for estimation of the nucleolar vv was very high; more than 95% of the totally observed variation was contributed by biologic differences between tumors. Single-term Cox analyses demonstrated a highly significant prognostic value of all five investigated, quantitative variables. Evaluation in a multivariate Cox model showed, however, that only the nucleolar vv and the largest tumor dimension were independent prognostic covariates at the chosen level of significance (5%). Unbiased, shape-independent estimates of the nucleolar vv offered superior prediction of clinical outcome, as compared with lower-dimensional, shape-dependent histomorphometric estimators of nucleolar size. PMID- 8491492 TI - Significance of pericryptal fibroblasts in colorectal epithelial tumors: a special reference to the histologic features and growth patterns. AB - We analyzed the appearance of pericryptal fibroblasts (PCFs) identical to myofibroblasts in human colorectal epithelial tumors (adenomas, carcinomas) by an immunohistochemical method, with special reference to the histologic features and tumor growth patterns. The majority (61.5%) of adenomas contained well-developed PCFs. In contrast, carcinomas contained more poorly developed PCFs than adenomas. Approximately one third (35.4%) of the intramucosal and most (89.6%) of the submucosal carcinoma components had poorly developed PCFs. Pericryptal fibroblast development in pure carcinomas also was evaluated in association with two types of tumor growth patterns: polypoid growth carcinoma (PG-Ca) and nonpolypoid growth carcinoma (NPG-Ca). Polypoid growth carcinoma tended to contain well developed PCFs, whereas NPG-Ca tended to lack PCFs. From the above findings, it is suggested that PCFs gradually decrease in the sequence of adenoma, intramucosal carcinoma, and submucosal invasive carcinoma. In addition, the two growth types (PG-Ca and NPG-Ca) are histologically different in PCF development, and the lack of a PCF network in NPG-Ca seems to be the reason why NPG-Ca can invade the submucosa more easily than PG-Ca, which has a consistent PCF network. PMID- 8491493 TI - Acquired immunodeficiency syndrome-like illness associated with systemic Mycoplasma fermentans infection in a human immunodeficiency virus-negative homosexual man. AB - A 35-year-old homosexual man developed a composite nodal Kaposi's sarcoma and peripheral T-cell lymphoma that were associated with a peripheral blood CD4 positive lymphocyte count of only 43/mm3. The patient subsequently developed Pneumocystis carinii pneumonitis and eventually died due to disseminated Cryptococcus neoformans. Numerous premortem tests for the presence of human immunodeficiency virus (HIV) types 1 and 2 were negative by the enzyme-linked immunosorbent assay, Western blot, viral isolation, and polymerase chain reaction techniques. Postmortem evaluations for HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-I, and HTLV-II also were negative by polymerase chain reaction, immunofluorescence assays, and viral isolation. A systemic infection by Mycoplasma fermentans, however, was documented by immunohistochemistry and polymerase chain reaction in premortem and postmortem tissues. This recently recognized human pathogen has produced systemic infections in patients with the acquired immunodeficiency syndrome (AIDS) and in previously healthy non-AIDS patients who characteristically have a fulminant flu-like illness. Additionally, M fermentans has enhanced the cytopathic effect of HIV in in vitro studies and has produced fatal wasting illnesses with terminal lymphopenia in inoculated adult silvered leaf monkeys. This report is the first description of an association between M fermentans infection and an AIDS-like illness in an HIV negative individual. The etiology of the severe immunosuppression in this patient and the associated role of M fermentans remain to be determined by further investigations. PMID- 8491494 TI - Monocytoid B-cell lymphoma with a distinctive clinical presentation. AB - Monocytoid B-cell lymphoma (MBCL) is a recently described non-Hodgkin's lymphoma. Patients with MBCL usually present with localized or generalized lymphadenopathy; peripheral blood and bone marrow involvement is rare. Patients with leukemic manifestations typically have advanced disease with extensive lymph node and bone marrow involvement. We report a distinctively unusual case of MBCL with peripheral blood and splenic involvement at presentation and with no evidence of peripheral lymph node disease. This case emphasizes the fact that malignancies of monocytoid B cells should be viewed as a spectrum of disease that ranges from leukemia to lymphoma. This feature is similar to other low-grade B-cell neoplasms, such as chronic lymphocytic leukemia/small cell lymphoma, lymphocytic type. PMID- 8491495 TI - Benign to malignant transformation in epithelial ovarian tumors. PMID- 8491496 TI - Reflex sympathetic activation induces acute insulin resistance in the human forearm. AB - Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg.dL-1.min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg.dL-1.min-1 per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%, p < 0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%, p < 0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491497 TI - Characteristics of arterial myosin in experimental renal hypertension in the dog. AB - We compared myosin samples isolated from iliac-femoral arteries of control and renal (stenosis) hypertensive dogs to determine the effects of increased blood pressure on the characteristics of the myosin. The ratio of 204-kd (SM-1) to 200 kd (SM-2) myosin heavy chains was approximately 1:0.75 for myosin from the iliac femoral artery of normotensive dogs. This was not altered significantly in response to hypertension. Both SM-1 and SM-2 myosin heavy chains cross-reacted with antibody against smooth muscle myosin on Western blot analysis. In addition to these heavy chains, purified myosin from both groups showed a very faint protein band slightly below the 200-kd myosin heavy chain on electrophoresis on a highly porous sodium dodecyl sulfate-polyacrylamide gel. This protein band cross reacted with antibody against nonmuscle myosin but not with smooth muscle myosin antibody. The 20- and 17-kd light chains of myosin isolated from normotensive and hypertensive dogs gave similar results on isoelectric focusing. Peptide maps of tryptic digests of heavy chains revealed both quantitative and qualitative differences. The Ca(2+)-activated myosin ATPase activity measured in high salt (0.5 mol/L KCl) was similar for myosin from both groups, whereas the potassium (ethylenedinitrilo)tetraacetic acid-stimulated ATPase of myosin from hypertensive animals was higher than that from normotensive animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491498 TI - Properties of the random zero sphygmomanometer. AB - The random zero sphygmomanometer is widely used in studies involving blood pressure measurement because it is believed to eliminate digit preference and reduce measurement error. We performed blood pressure measurements sequentially using random zero and standard sphygmomanometers in random order in 1,356 participants in the Cardiovascular Health Study. Despite adherence to the manufacturer's instructions, we observed a substantially nonuniform distribution of zero levels generated by the random zero sphygmomanometer and a disturbing correlation between the zero level and blood pressures taken with the standard sphygmomanometer. With the random zero device, the pooled estimated slopes for the regression of standard systolic and diastolic pressures on the zero level were -0.71 and -0.17, respectively (both p < 0.0001). The only plausible explanation for this relation between the random zero device and the standard device is that by some unknown mechanism the subject's blood pressure is influencing the zero level. Systolic and diastolic blood pressures measured with the random zero device were, respectively, 1.65 and 1.84 mm Hg lower (both p < 0.0001) than standard blood pressures. Digit preference was detectable in the uncorrected blood pressure and zero level measured with the random zero device but was eliminated after calculation of the corrected blood pressure. For most epidemiological studies, the random zero sphygmomanometer offers no significant advantage over the standard sphygmomanometer. It may still be useful in those epidemiological studies and clinical trials where blinding is important. PMID- 8491499 TI - Elevated hepatic insulin extraction in essential hypertension. AB - Insulin resistance, hyperinsulinemia, and dyslipidemia are common characteristics of patients with untreated hypertension. However, the link between the vascular and metabolic disturbances is still unclear. To provide further insights into the metabolic picture of subjects with hypertension, we evaluated insulin resistance, pancreatic secretion, and hepatic extraction of the hormone in 16 untreated patients with essential hypertension before and after 12-16 weeks of drug treatment in comparison with 16 age-, sex-, and body weight-matched normotensive control subjects. All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. Metabolic parameters were calculated by the minimal model technique. The hypertensive patients exhibited a highly reduced tissue insulin sensitivity (2.6 +/- 0.4 versus 9.6 +/- 1.9 10(4) min 1/[microunits/mL]; p < 0.001). The basal secretion rate (70 +/- 11 versus 35 +/- 5 pmol/L per minute) and the total amount of prehepatically secreted insulin (32 +/- 4 versus 16 +/- 2 nmol/L in 4 hours) were significantly increased in the hypertensive patients compared with the control subjects (p < 0.01), whereas the posthepatic insulin delivery rate was not significantly different between the two groups (4.9 +/- 0.6 versus 3.5 +/- 0.3 nmol/L in 4 hours). Hepatic insulin extraction was found to be significantly elevated in the hypertensive patients compared with control subjects (81 +/- 4% versus 69 +/- 3%, p < 0.04). Increased hepatic insulin extraction partially ameliorated B cell hypersecretion in hypertensive patients. After 12-16 weeks of drug treatment, the blood pressure was normalized, but the metabolic profile of the patients remained unchanged. We conclude that elevated insulin extraction in the liver is a specific characteristic of individuals with essential hypertension and partially compensates pancreatic B cell hypersecretion. PMID- 8491500 TI - Epidermal growth factor is a potent inhibitor of renin secretion. AB - Epidermal growth factor (EGF) is not only a cell mitogen but a potent vasoconstrictor that shares many properties with angiotensin II. Because EGF is localized in the kidney, we have studied the direct effects of EGF on renin secretion using both static incubations and perifusions of rat renal cortical slices. EGF at 5 x 10(-9) M significantly inhibited renin secretion in static incubations (control, 100 +/- 3%; EGF, 72 +/- 3%; p < 0.001). When added to perifusions, EGF acted rapidly, reducing renin secretion at the earliest time period (10 minutes). Similarly, transforming growth factor-alpha, which can bind to the EGF receptor, also inhibited renin secretion (control, 92 +/- 8%; transforming growth factor-alpha [2 x 10(-9) M], 63 +/- 4%; p < 0.02). Because both prostaglandins and lipoxygenase products of arachidonic acid have been shown to play a role in some EGF-mediated actions, we examined these possible mechanisms of EGF action. Meclofenamate, a cyclooxygenase blocker, and BW755c and baicalein, both lipoxygenase blockers, were studied. None of these agents altered EGF-mediated renin inhibition. EGF action has also been coupled to the stimulation of tyrosine kinase activity; therefore, we examined the effects of the tyrosine kinase inhibitors genistein and quercetin. Both genistein (10(-5) M) and quercetin (10(-5) M) abolished the inhibition of renin by EGF (control, 100 +/- 3%; EGF, 82 +/- 4%; EGF plus genistein, 110 +/- 7%; p < 0.01; EGF, 75 +/- 4%; EGF plus quercetin, 92 +/- 4%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491501 TI - Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension. AB - Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension. PMID- 8491502 TI - Autonomic modulation of contractions to endothelin-1 in canine coronary arteries. AB - Endothelin-1 contracts vascular smooth muscle and inhibits release of neurotransmitter from adrenergic and cholinergic neurons. Experiments were designed to investigate the interaction of these mechanisms in a blood vessel that receives both adrenergic and cholinergic innervation. Rings cut from canine left anterior descending coronary arteries were suspended in organ chambers for the measurement of isometric force. In some rings, the endothelium was removed. Endothelin-1 caused concentration-dependent increases in tension in all rings. During electrical stimulation (1 Hz, 9 V, 2 msec), the contractions to endothelin 1 were reduced significantly. In rings without endothelium, this decrease was greater in the presence of atropine (10(-6) M) and was eliminated by a combination of phentolamine (10(-5) M) and propranolol (5 x 10(-6) M). Contractions to endothelin-1 during electrical stimulation in rings with endothelium were significantly less than those without endothelium. This difference was eliminated by atropine and NG-monomethyl L-arginine (10(-4) M). The presynaptic effects of endothelin-1 were studied by measurement of tritium labeled norepinephrine. Phasic electrical stimulation induced release of norepinephrine; this was inhibited by endothelin-1 at high concentrations (4 x 10(-7) M) in the presence of atropine. These results suggest that the major effect of endothelin-1 is postsynaptic in canine coronary arteries. However, contractions to endothelin-1 may be modulated by the level of sympathetic and parasympathetic tone. In situations in which innervation to the coronary arteries is altered, for example, in hearts used for transplantation, the contractile effects of endothelin-1 would prevail. PMID- 8491503 TI - Acute alcohol administration stimulates baroreceptor discharge in the dog. AB - It has been shown that alcohol administration causes baroreceptor reflex inhibition. The site of action of alcohol could reside anywhere within the baroreceptor reflex arc. Therefore, the goal of this study was to determine the effects of acute administration of alcohol on carotid sinus baroreceptor discharge characteristics. In pentobarbital-anesthetized dogs, the carotid sinus was isolated and perfused. Single unit baroreceptor discharge was recorded from the carotid sinus nerve along with carotid sinus diameter using sonomicrometry. Carotid sinus pressure-baroreceptor discharge and carotid sinus pressure-diameter curves were constructed. Perfusion of the carotid sinus with alcohol (100 mmol/L) significantly decreased the pressure threshold from 91.1 +/- 2.8 to 86.4 +/- 2.9 mm Hg (p < 0.05) and increased the peak discharge rate from 45.8 +/- 3.4 to 52.8 +/- 3.6 spikes per second (p < 0.01). The same phenomenon was seen during perfusion of the carotid sinus with acetaldehyde (2.5 mmol/L) but was not seen during perfusion with acetate (2.5 mmol/L). During perfusion of the carotid sinus with alcohol, the carotid sinus pressure-carotid sinus diameter relation did not change. The baroreceptor sensitization induced by alcohol is not an endothelium dependent mechanism, because endothelial denudation did not block this alcohol induced effect. Measurement of the duration of postexcitatory depression of carotid sinus baroreceptors, which is related to Na+,K(+)-ATPase activity, showed that perfusion of the carotid sinus with alcohol or acetaldehyde significantly reduced the duration of postexcitatory depression, indicating that the alcohol- and acetaldehyde-induced effect on baroreceptor discharge is most likely mediated by an inhibition of Na+,K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491504 TI - Influence of endogenous angiotensin on the renovascular response to norepinephrine. AB - The purpose of this study was to elucidate the role of endogenous angiotensin II in mediating the renovascular effects of renal adrenergic stimulation. Six conscious dogs instrumented for monitoring of renal blood flow were subjected to step increases every 10 minutes in the rate of norepinephrine infusion into the renal artery. Under control conditions, infusion of norepinephrine (10-40 ng/min per milliliter per minute of control renal blood flow) increased plasma renin activity and decreased renal blood flow progressively by approximately 10-75%. When increments in angiotensin II during norepinephrine infusion were abolished by fixing plasma levels of angiotensin II at either normal or high concentrations by chronic infusion of captopril plus angiotensin II, renal blood flow responses to adrenergic stimulation were greatly attenuated at rates of norepinephrine infusion that decreased renal blood flow up to approximately 40% under control conditions. Thus, acutely generated angiotensin II appeared to contribute to the renovascular effects of norepinephrine. However, when endogenous levels of angiotensin II were suppressed to low levels by chronic infusion of captopril alone, norepinephrine induced severe renal ischemia at much lower rates of infusion than occurred when the renin-angiotensin system was intact. Since this enhanced sensitivity to norepinephrine did not occur during chronic captopril infusion when angiotensin II was given simultaneously at rates that restored mean arterial pressure to normotensive levels or higher, low arterial pressure during chronic captopril administration may predispose the kidneys to excessive renal vasoconstriction during renal adrenergic stimulation. PMID- 8491505 TI - Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers. AB - Losartan is an orally active, nonpeptide angiotensin II (Ang II) (site-1) receptor antagonist. We conducted a multiple-dose study in healthy male volunteers to investigate the tolerability, blood pressure effects, and changes in plasma renin activity (PRA) and plasma Ang II concentration associated with once-daily administration of 100 mg losartan for a week. Subjects were studied on a standardized sodium diet (24-hour urinary sodium excretion, 98 +/- 37 [SD] mEq per 24 hours on the placebo run-in day). Measurements of blood pressure, heart rate, PRA, Ang II, and aldosterone were taken during a placebo run-in day and after single and multiple (7 days) daily doses of losartan (100 mg, n = 10) or placebo (n = 4). Ang II was measured specifically by high performance liquid chromatography coupled with radioimmunoassay. In subjects given losartan, respective decreases (systolic/diastolic) from run-in in supine blood pressure 6 hours after dosing were (mean +/- SD), compared with the placebo run-in day, first dose: -8.8 +/- 9.6/-6.8 +/- 5.0, last dose: -11.6 +/- 8.9/-7.0 +/- 4.8 mm Hg (p < 0.05 for all changes). At this 6-hour time point, corresponding increases from run-in in PRA were from 1.2 +/- 0.6 to 12.0 +/- 6.3 (first dose) and 9.6 +/- 4.9 (last dose) ng angiotensin I per milliliter per hour and in Ang II were from 4.3 +/- 1.7 to 72.4 +/- 33.3 and 45.7 +/- 14.1 pg/mL. All changes in PRA and Ang II were statistically significant within the losartan-treated group, and the biochemical changes were significantly greater than those in the placebo-treated group. The increment in Ang II was less after the last dose than after the first (p < 0.05). The drug was well tolerated by all subjects. These data indicate that, under the conditions of this study, losartan administration (100 mg/day for eight doses over 9 days) results in treatment-related decreases in blood pressure and increases in PRA and Ang II octapeptide. PMID- 8491506 TI - Psychosocial stress can induce chronic hypertension in normotensive strains of rats. AB - We report on five 6-month experiments during which five colonies of four male and four female rats were exposed to psychosocial stress. Monthly blood pressure measurements by a tail-cuff method showed a modest (10 mm Hg) increase in two studies using Sprague-Dawley rats. In two further studies using the more aggressive Long-Evans strain, terminal direct carotid arterial pressures were taken as well, and in one study the differences exceeded 20 mm Hg. A fifth study used the Wistar-Kyoto, hyperactive (WKHA) strain developed by Hendley, and no differences were observed. Heart and adrenal weights; adrenal catecholamine synthetic enzymes; and heart, aortic, and kidney histology were measured and showed significant changes, which for the most part paralleled blood pressure changes. Social instability and the associated blood pressure changes were made more severe by periodic mixing of males from different colonies. This had no effect on the peaceable WKHA rats, some effect on the Sprague-Dawley rats, and a severe effect on the Long-Evans rats. The WKHA rats failed to show blood pressure changes despite stress-induced increases in heart and adrenal weights. Thus, different types of psychosocial stress and different genetics combine to induce a variety of neuroendocrine changes, not all of which necessarily lead to increased blood pressure. PMID- 8491507 TI - Sodium retention and hypertension after kidney transplantation in rats. AB - The present study was designed to investigate the development of blood pressure and renal sodium handling in recipients of renal grafts from adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and borderline hypertensive F1 hybrids bred from SHRSP and WKY rats. Unilaterally nephrectomized F1 hybrids served as renal graft recipients. The second native kidney was removed 7 days after transplantation. Starting on the day of transplantation, renal graft recipients were put on a standard diet for 7 days followed by a low salt diet (0.18% salt) for 10 days and a high salt diet (1.8% salt) for another 14 days. In recipients of a renal graft from SHRSP donors, systolic blood pressure rose progressively from 140 +/- 4 mm Hg before to 190 +/- 7 mm Hg 4 weeks after transplantation. In contrast, in recipients of a renal graft from WKY rat donors, blood pressure fell during the same time from 139 +/- 7 mm Hg to 120 +/- 4 mm Hg. Blood pressure did not change significantly in recipients of a renal graft from F1 hybrid donors (132 +/- 4 versus 138 +/- 7 mm Hg). With transition from a low salt to high salt diet, all rats exhibited renal sodium retention. The accumulating amount of sodium retained by the renal graft was significantly higher in recipients of an SHRSP kidney than in recipients of a WKY rat kidney at all days on the high salt diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491508 TI - Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat. AB - Prior studies describe deficiencies of T-cell-mediated immunity in the spontaneously hypertensive rat (SHR) strain of Okamoto and Aoki. This report describes an alteration of humoral immunity: elevation of the plasma concentration of immunoglobulin (Ig) A and of circulating IgA autoantibodies to single-stranded DNA, double-stranded DNA, and thyroglobulin. The increased plasma IgA levels are evident in prehypertensive SHR, hence not secondary to the hypertension, and they result mainly from increments in polymeric IgA. Plasma IgA content also varied concordantly with the level of systolic blood pressure as influenced by age (older > younger) and gender (male > female) in both the SHR and control Wistar-Kyoto rat strains. Strain differences in plasma IgG or IgM were not observed. Studies of peripheral blood lymphocytes indicate that increased production of IgA is one mechanism for the increment in plasma content. The number of blood lymphocytes capable of producing IgA in vitro in response to the mitogen lipopolysaccharide is increased in SHR. When cultured in the absence or presence of lipopolysaccharide, peripheral blood lymphocytes of SHR secrete more IgA in vitro than do cells of the control strain. No significant strain differences in biliary or renal excretion of IgA were observed. The observed alterations of IgA in the SHR either are causative factors in the development of the hypertension or are the products of an epiphenomenon in which IgA and blood pressure are affected separately, but in parallel, by causative factors related to rat strain, age, and gender. PMID- 8491509 TI - Metabotropic glutamate receptors in the ventrolateral medulla of rats. AB - We investigated the hypothesis that stimulation of metabotropic excitatory amino acid receptors in the ventrolateral medulla evokes cardiovascular responses. Thus, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic excitatory amino acid receptors, was microinjected into the rostral or caudal ventrolateral medulla of halothane anesthetized Sprague-Dawley rats. Microinjections of (1S,3R)-ACPD (100 pmol-1 nmol) into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure (+20 +/- 4 mm Hg by 100 pmol and +35 +/- 2 mm Hg by 1 nmol, p < 0.01 versus artificial cerebrospinal fluid) and integrated splanchnic sympathetic nerve activity (+17 +/- 3% and +46 +/- 4%, respectively, p < 0.01), whereas (1S,3+)-ACPD microinjected into the caudal ventrolateral medulla decreased mean arterial pressure (-28 +/- 2 mm Hg by 100 pmol and -48 +/- 6 mm Hg by 1 nmol, p < 0.01 versus artificial cerebrospinal fluid) and splanchnic sympathetic nerve activity (-24 +/- 4% and -49 +/- 5%, p < 0.01). The blockade of ionotropic excitatory amino acid receptors by the combined injection of 2-amino-7 phosphonoheptanoic acid (200 pmol) and 6,7-dinitroquinoxaline-2,3-dione (200 pmol), which effectively blocked the responses elicited by either N-methyl-D aspartate (20 pmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol), failed to affect the responses evoked by either (1S,3R)-ACPD (100 pmol) or L-glutamate (2 nmol) microinjected in the rostral and caudal ventrolateral medulla. These results suggest that metabotropic receptors are present and mediate cardiovascular responses evoked by L-glutamate injections into the rostral and caudal ventrolateral medulla. PMID- 8491510 TI - Antiinflammatory action of thielocin A1 beta, a group II phospholipase A2 specific inhibitor, in rat carrageenan-induced pleurisy. AB - Extracellular phospholipase A2 (PLA2) activity was detected in exudate from rat carrageenan-induced pleurisy using [3H]oleic acid-labeled Escherichia coli as substrate. Both exudate volume and PLA2 activity increased up to 24 h after carrageenin injection. Specific absorption of this activity by anti-group II PLA2 (PLA2-II) antibody indicated that the PLA2 activity in the pleural exudate was PLA2-II. Thielocin A1 beta, a novel type of PLA2 inhibitor from fungi, inhibited this PLA2-II activity in a dose-dependent manner (IC50 = 0.32 microM). Thielocin A1 beta correspondingly reduced both exudate volume and PLA2-II activity in the exudate in a dose-dependent manner when coinjected with carrageenan. The exudate volume was also significantly decreased when indomethacin, a cyclooxygenase inhibitor, or dexamethasone, a steroidal antiinflammatory drug, was coinjected with carrageenan. However, neither indomethacin nor dexamethasone could significantly attenuate the PLA2-II activity in exudate. In addition, indomethacin and dexamethasone significantly reduced the levels of PGE2 in the exudate. However, thielocin A1 beta had no effect on the PGE2 content in the exudate. These results suggest that thielocin A1 beta shows antiinflammatory activity due to inhibition of PLA2-II and offer evidence for the significance of PLA2-II in the propagation of inflammatory processes. PMID- 8491511 TI - Effect of treatment with interleukin-1 receptor antagonist on the development of carrageenan-induced pleurisy in the rat. AB - Pretreatment of rats with the human interleukin-1 receptor antagonist (IL-1ra) by the subcutaneous route at -0.5 h, relative to the intrapleural injection of carrageenan (CG), suppressed the infiltration of cells into the pleural cavity of intact and adrenalectomized rats at 5 h (28 and 74% reduction in intact animals at 0.3 and 10 mg/kg, respectively). Exudate volume at 5 h was also suppressed at dosages of IL-1ra > or = 3 mg/kg. IL-1ra was still effective as an antiinflammatory agent in the 5-h pleurisy model when administered 1 or 2 h, but not 3 h, after CG. The addition of IL-1ra to a maximally effective antiinflammatory dosage of indomethacin (5 mg/kg) resulted in further reductions of cell number and exudate volume, suggesting that the antiinflammatory effects of IL-1ra in the 5-h model were not due solely to inhibition of IL-1-induced prostaglandin biosynthesis. The antiinflammatory effects of suboptimal dosages of IL-1ra and dexamethasone, administered in combination, were essentially additive. In 24-h pleurisy, IL-1ra reduced exudate volume and PMN number after a single dosage of 10 mg/kg, subcutaneously at -0.5 h and after dosages of 3 mg/kg at -0.5 and 5 h. Additional dosages of IL-1ra (3 mg/kg) at 10 and 15 h did not further inhibit PMN accumulation. Treatment with IL-1ra did not affect macrophage accumulation in 24-h CG-induced pleurisy. IL-1ra was not active as an antiinflammatory agent in the 24-h pleurisy model after three dosages of IL-1ra (3 mg/kg) at 5, 10 and 15 h. PMID- 8491512 TI - Alteration in rat apolipoprotein C-III gene expression and lipoprotein composition during inflammation. AB - A cloned rat apolipoprotein (apo) C-III cDNA was used as a hybridization probe to measure apo C-III mRNA levels in rats after induction of inflammation. Hepatic apo C-III mRNA levels decrease to a minimum value of 46% of normal 72 h after the induction of inflammation. The changes observed are very similar to the changes in mRNA levels of rat apo A-IV, while the hepatic mRNA levels for apo A-I and apo C-I during inflammation remain relatively constant. Alterations in apo C-III gene expression during inflammation were associated with changes in lipoprotein particle size and composition. A decrease of approximately twofold in the amount of apo C-III-containing HDL particles was found in rats 24 h after the induction of inflammation. The average size of apo C-III-containing HDL particles in rats during inflammation is significantly larger than that of the control group. A decrease in the concentration of apo A-I-containing HDL particles was also observed in these rats. The results indicate altered apolipoprotein gene expression associated with alterations in the size and composition of HDL particles. PMID- 8491513 TI - Tissue distribution of angiotensinogen mRNA during experimental inflammation. AB - It has been proposed that angiotensinogen is an acute phase protein, because its plasma concentrations increase during some forms of acute inflammation. However, this is not a consistent finding. Furthermore, no specific function of circulating angiotensinogen in the inflammatory reaction is known. This may be different for extrahepatic synthesis of angiotensinogen, as the local generation of angiotensin II has been implicated in inflammation-related processes in some organs. We have therefore examined the expression of the angiotensinogen gene in liver and extrahepatic tissues under the influence of experimental inflammatory stimuli in comparison to the effects of dexamethasone. Dexamethasone (7 mg/kg intraperitoneally) induced a several-fold increase in angiotensinogen mRNA in liver, aorta, heart, adrenal, and a moderate increase in kidney, testis, and brain. Plasma concentrations of angiotensinogen, alpha 1-acid glycoprotein, and alpha 2-macroglobulin increased, whereas albumin concentrations decreased. Lipopolysaccharide (500 micrograms/kg subcutaneously) stimulated angiotensinogen mRNA in hepatic, cardiac, renal, adrenal, and testicular tissues, but not in the brain. Plasma concentrations of angiotensinogen, alpha 1-acid glycoprotein, and alpha 2-macroglobulin increased, those of albumin decreased. In turpentine treated rats (5 ml/kg subcutaneously), angiotensinogen mRNA was reduced in liver and kidney; stimulated in adrenals, testis, and heart; and not influenced in the brain. Plasma concentrations of the acute phase proteins increased, whereas angiotensinogen and albumin decreased. It is concluded that hepatic and extrahepatic angiotensinogen gene expression seem to be regulated similarly by dexamethasone and lipopolysaccharide. The different response to turpentine may reflect differences in the pattern of cytokines induced by turpentine or be associated with additional pharmacological effects of turpentine or its metabolites. PMID- 8491514 TI - Increased serum catalase activity in rats subjected to thermal skin injury. AB - We found that rats subjected to thermal skin injury (burn) had increased serum hydrogen peroxide (H2O2) scavenging activity, serum catalase activity, erythrocyte (RBC) fragility, and edematous lung injury (lung leak) when compared to sham-treated rats. Serum H2O2 scavenging activity was inhibited by addition of sodium azide, a catalase inhibitor. Treatment of rats with the oxygen radical scavenger, dimethylthiourea (DMTU), decreased RBC fragility and lung leak but did not alter increased H2O2 scavenging or catalase activity of serum from rats subjected to skin burn. We conclude that increased serum catalase activity is a consequence of thermal skin injury and that increased serum catalase activity may be a mechanism that modulates H2O2-dependent processes following skin burn. PMID- 8491515 TI - Swine as a model of skin inflammation. Phospholipase A2-induced inflammation. AB - A predictive animal model of skin inflammation is needed for the development of potential therapeutic agents. The existing models of inflammation rely on animals whose skin physiology or biochemistry differs significantly from human. The objective of this investigation was to evaluate the swine as a potential model of inflammation, because its skin has been recognized to exhibit morphologic and functional similarities to human skin. In the swine, an inflammatory response was produced following intradermal injection of snake venom phospholipase A2 (PLA2). This response was characterized by transient erythema (2-3 h) and microscopic changes of cell infiltration, epidermal hyperplasia, and dermal damage, which were apparent two days after PLA2 and peaked by day 7. In general, these microscopic changes persisted up to 21 days. Treatment with the antiinflammatory steroid, betamethasone dipropionate (Diprolene), gave a significant reduction of the inflammatory responses. Heat-inactivated PLA2, ovalbumin, or saline did not provoke this reaction, although PLA2 inactivated by bromophenacyl bromide alkylation did produce an inflammatory response. The alkylated PLA2 was also able to provoke an inflammatory response in the mouse paw edema assay. These results demonstrate that PLA2 can stimulate an inflammatory response in the swine skin, but that phospholipid hydrolytic activity is not required. PMID- 8491516 TI - Expression of tumor necrosis factor and c-fos genes in peritoneal macrophages of hypothyroid mice. AB - It is well documented that hypothyroid patients are more susceptible to microbial infections. In order to study whether this impaired response is due to a decrease in production of antitumor molecules or an impaired ability to transmit information in the macrophage, a hypothyroid animal model was used to study the expression of both tumor necrosis factor gene and c-fos protooncogene in peritoneal macrophages. Inbred mice were rendered hypothyroid by an antithyroid drug, methimazole, and the expression of tumor necrosis factor gene and c-fos protooncogene in peritoneal macrophages were studied. Impairment of c-fos and TNF genes were at both transcriptional and translational levels using northern blot analysis, bioassays, and immunocytochemical staining methods. These results indicate that the reduction in signal transduction and in the production of antitumor molecules may cause the poor defense ability of hypothyroid animals. PMID- 8491517 TI - Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model. AB - As part of the characterization of the host reactivity to the venom of Bothrops asper, we investigated the inflammatory responses in the mouse footpad model. The subcutaneously injected venom induced a rapid increase of serum IL-6 concentration, which peaked between 3 and 6 h and returned to normal values at 12 h. In contrast, serum TNF-alpha and IL-1 alpha were not detectable at any time point studied. A myotoxic phospholipase A2 isoform purified from this venom, myotoxin II, was also able to induce a systemic IL-6 release when injected into the footpad. Both venom and myotoxin induced local edema and a leukocyte infiltrate accumulating in the muscle and subdermal tissue within 6 h. The infiltrate consisted predominantly of neutrophils at 6 and 24 h, but at later times, mononuclear cells also appeared. The edema, leukocyte infiltration, and IL 6 responses did not depend on the hemorrhagic activity of venom, since all three effects were seen after injection of (1) preneutralized venom, devoid of hemorrhagic activity, and (2) purified myotoxin II. Circulating platelet numbers were significantly decreased 30 min after venom injection and returned to normal after 12 h. The venom also induced a rapid inversion in the ratio of neutrophils to lymphocytes in peripheral blood, which did not normalize until 12 h later. The present observations suggest that venom, besides its cytotoxic properties, induces early hematologic and immunologic alterations. These findings may be of relevance in future treatment modalities. PMID- 8491518 TI - Three-year prevalence of enteropathogenic bacteria in an urban patient population in Germany. AB - The prevalence of enteropathogenic bacteria over a three-year period was 3.1% in an urban population in Germany. Nontyphoidal Salmonella spp. (1.8% prevalence) represented 59.3% of all positive isolates, followed by Campylobacter spp., which constituted 22.1% of such isolates. Clostridium difficile toxin was detected in 5.6% of samples submitted specifically for detection of cytotoxigenic C. difficile. The seasonal distribution showed an increase of Salmonella, Shigella and Aeromonas/Plesiomonas isolates in the post-holiday season, partly due to returning travelers. An epidemic five-fold increase of Salmonella enteritidis isolates was found over the three-year-period. Enteropathogenic bacteria such as Salmonella, Campylobacter and cytotoxigenic C. difficile were common etiologic agents of gastrointestinal tract infections in patients with AIDS. We conclude that travelers and HIV-infected subjects are especially prone to infection with enteropathogenic bacteria; preventive measures to control the Salmonella enteritidis epidemic are essential. PMID- 8491519 TI - Measles associated hepatobiliary disease: an overview. AB - In this report the literature on all cases of documented measles with hepatobiliary disease was reviewed to describe the characteristics of measles associated hepatitis. We found 27 patients described. Their age ranged from 9 to 59 years. Male to female ratio excluding military facilities was 1:1. The clinical and laboratory presentation appeared to follow one of two patterns. The first was suggestive of hepatocellular dysfunction characterized by aminotransferase elevation. It was encountered in 24/27 cases, seven of them with atypical measles. This form of liver disease tended to be asymptomatic. It appeared early and resolved in a few days. The second pattern was characterized by cholestasis and jaundice. It was described in three cases. This type of hepatitis became apparent when measles began to recede and persisted for two weeks or longer. The variation in time of appearance of the two types of liver disease may imply distinct pathogenetic mechanisms. PMID- 8491520 TI - Congenital rubella syndrome after maternal reinfection. AB - This report concerns a case of congenital rubella syndrome (CRS) with atypical immune response affecting an infant whose mother had repeated evidence of immunity before pregnancy. Laboratory diagnosis of CRS could only clearly be achieved by virus isolation after the second month of life despite typical clinical features of CRS and multiple organ involvement. After the first month of age, low concentrations of specific IgM antibodies were revealed by ELISA and confirmed by a reference test system (IgM-specific haemagglutination inhibition assay). Persistent and increasing high levels of IgM antibodies were detected only after the 6th month of life. Later on IgG antibody levels decreased. Immunological investigations showed an IgG1-hypoglobulinaemia. The unusual feature of the present case report is not only the failure of the maternal rubella immunity to prevent CRS, but the defect of the child's immune system, probably attributable to congenital infection. As a consequence, laboratory diagnosis of CRS could not be achieved initially by the proved serological methods. PMID- 8491521 TI - Shigellemia in AIDS patients: case report and review of the literature. AB - Shigella bacteremia in adult patients is rare and is usually associated with immunosuppressive diseases. To date, 12 HIV-positive patients with Shigella bacteremia have been reported in the medical literature. We report a case of Shigella dysenteriae bacteremia in a 39-year-old HIV-positive patient. Although the patient presented with bloody and watery diarrhea, stool cultures failed to grow enteric pathogens. The patient responded well to appropriate antibiotic therapy. PMID- 8491522 TI - Listeria monocytogenes infection of a prosthetic vascular graft. AB - A 75-year-old man was admitted for acute ischaemia of his right leg for which he had undergone vascular prosthetic surgery at another hospital, ten and three years before. Cultures of the thrombosed graft and the clots removed on re operation were positive for Listeria monocytogenes. After parenteral treatment with amoxicillin-clavulanic acid and gentamicin, the patient died from cardiorespiratory failure. PMID- 8491523 TI - The in vitro inactivation of thirteen beta-lactam antibiotics by other mechanisms than adsorption to faecal substance. AB - We have investigated the antibiotic inactivating capacity of intestinal contents in vitro in faeces. In the presently reported study the influence of beta lactamase catalyzed hydrolysis on the antimicrobial activity of 13 commonly used beta-lactam antibiotics was investigated, while the influence of non-specific adsorption of antibiotics to faecal compounds was also taken into account. The following antibiotics were tested: benzylpenicillin, amoxicillin, amoxicillin/clavulanate, cloxacillin, piperacillin, temocillin, cefuroxime, cefamandole, cephradine, cefotaxime, ceftazidime, aztreonam and imipenem. Faecal samples were obtained from 30 healthy volunteers. Six different concentrations of each antibiotic were added to 1 g of faeces. After 24 h of incubation at 37 degrees C the remaining amount of active antibiotic was determined by means of a "growth inhibition assay". The contribution to the test results of non-specific adsorption to macromolecules was calculated by means of a model and the inactivation data were subsequently corrected. The amount of antibiotic non specifically bound to faecal macromolecules varied from 0% to 80% of the amount of antibiotic initially added to the faeces. A considerable difference was found in the degree of inactivation of several antibiotics. However, in contrast to earlier investigations, the results of this study show that in a normal population the influence of beta-lactamase catalyzed hydrolysis on the activity of beta-lactam antibiotics is apparently very small when compared to the influence of non-specific adsorption of beta-lactam antibiotics to faecal compounds. PMID- 8491524 TI - Pneumocystis carinii pneumonia in heart transplant recipients. AB - Seven cases of Pneumocystis carinii pneumonia (PCP) (two in 1988, three in 1989, one in 1990 and one in 1991) have been observed in a group of 241 heart transplant recipients transplanted in Pavia, Italy, from November 1985 through December 1991. Median time to onset of symptoms was 100 days after transplantation (range 59-333 days). Diagnosis was achieved in all patients by cytological examination of bronchoalveolar lavage (BAL) fluid and/or transbronchial biopsy. Clinical and roentgenographic features were remarkably similar in all PCP-affected heart transplant recipients. A dry, persistent hacking cough associated with dyspnoea was consistently observed. Fever ranged from 37.6 to 39.4 degrees C, median leukocyte count and median arterial oxygen saturation (SaO2) values were 7,300/mm3 (range 3,000-16,000/mm3) and 61% (range 49.3-93%), respectively. Median CD4+ count at the onset of symptoms was 211/mm3 (range 28-739/mm3). The only patient experiencing a recurrence of PCP had a CD4+ cell count of 28/mm3 at the end of treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In all patients human cytomegalovirus was isolated from BAL fluids; however, treatment with TMP-SMX alone (20 mg/kg/day of TMP) was consistently followed by a complete recovery. PMID- 8491525 TI - Prevalence of hyperimmunization against tetanus in Italians born after the introduction of mandatory vaccination of children with tetanus toxoid in 1968. AB - Systematic mandatory immunization of children against tetanus was started in Italy in 1968. Prevalence of tetanus hyperimmunization (> 5 IU/ml) was assessed among 214 immune subjects born after 1968 and found to be 17.3%. This figure is significantly higher (p < 0.01) than the 10.8% found in a previous study of subjects born before 1968. This increase is statistically significant in the Center (p < 0.01) and in the South (p < 0.05) of Italy, but not in the North. Hyperimmunization is not associated with family size (odds ratio 2.16; C. I. 95% = 0.5-7.6) or the father's years of education (odds ratio 1.83; C. I. 95% = 0.6 5.3). No difference was found between urban and rural areas of residence. Indiscriminate administration of booster doses of tetanus vaccine in hyperimmune subjects in some areas could result in unnecessary vaccinations, which can cause hypersensitivity reactions. PMID- 8491526 TI - CSF shunt infections in children. AB - The incidence of shunt infections and possible risk factors was investigated by chart analysis. From 1986 to 1989 350 shunt procedures were performed including 273 ventriculoperitoneal shunts and 75 ventriculoatrial shunts. Twenty-eight infectious episodes (8%) occurred in 25 patients during a median follow-up time of 20 months. For 204 patients the follow-up time could be prolonged until September 1992. In these patients no infectious episodes occurred in the extended observation period. In 24 cases (85.7%) a causative organism could be isolated. The infecting organisms were gram-positive cocci in 22 cases (78.6%) and gram negative bacilli in two cases. The main signs and symptoms were fever, shunt malfunction and meningeal irritation, and with VP-shunts only, abdominal pain. Twenty-four infectious episodes were treated with antibiotics and immediate removal of the shunt. The remaining were managed with antibiotics only. The risk for shunt infection did not correlate with age or sex of patients, nor with the etiology of hydrocephalus, type of shunt implanted or perioperative antibiotic prophylaxis. However, a trend showing a higher risk for shunt infections with prolonged operation time was noticed. The infection rate was 13.6% for an operation lasting more than 90 minutes versus 5.2% for procedures of less than 30 minutes duration. PMID- 8491527 TI - Penetration of ofloxacin into prostatic fluid, ejaculate and seminal fluid. AB - The penetration of ofloxacin into prostatic fluid, ejaculate and seminal fluid was measured by a high-pressure liquid chromatography (HPLC) method after intravenous infusion (60 min) of 400 mg in six healthy male volunteers. The median concentration of ofloxacin in prostatic fluid was about one-third and that in ejaculate and seminal fluid about twice that in corresponding plasma. The results of the study indicate good penetration of ofloxacin into prostatic fluid, ejaculate and seminal fluid. Ofloxacin should thus be of value for the treatment of chronic bacterial prostatitis and vesiculitis. PMID- 8491528 TI - Concepts of reality and psychic reality in psychoanalysis as illustrated by the disagreement between Freud and Ferenczi. AB - In this paper, the concepts of reality and psychic reality are discussed in relationship to a number of controversies about the therapeutic and scientific aims of psychoanalysis, as illustrated by the disagreement between Freud and Ferenczi. Because the nature of psychic reality is necessarily incomplete and indeterminate, there are inherent limitations and dangers to any psychoanalytic attempt to discover historical and experiential truth. Modell's interpretation of Nachtraglichkeit ('deferred action') as 'retranscription' expresses the ambiguity of psychic reality in analysis, which is not fixed or foundational but part of an evolving inner and outer dialogue in relation to new experience. It is argued that Freud accepted this ambiguity, while Ferenczi sought to overcome it through modifications of technique. PMID- 8491529 TI - Psychic conflict and the external world in Freud's theory of the instinctual drives in light of his adherence to Darwin. AB - Freud's theory of the instinctual drives is examined in the light of his adherence to Darwinian thought. In this scheme, the drives arise from the interaction between biological and environmental stimuli and are dialectically constructed from both pressures: internal and external phenomena reciprocally organise each other and attempts to conceptualise them as separate entities restrict the degree to which we can understand the nature of mental life. Inhibition that became built-in to biological stimuli redirected and 'elevated' these bodily urges to representational functioning, a phylogenetic process which developed from environmental demands in the species' struggle to survive. These ideas bear upon Freud's notion that ubiquitous mental conflict, environmental sensitivities, and primitive id and ego (including defence) organisations are inherent components of instinctual activity. This construction is compared to Freud's other models of the instinctual drives. The attitude conveyed by the metapsychological suppositions put forward is related to the clinical situation. PMID- 8491530 TI - Primitive object love in Melanie Klein's thinking; early theoretical influences. AB - Melanie Klein's thinking on early object love is pivotal to her vision of development. Yet within her texts it is often enmeshed in complex formulations that obscure its full significance. A greater clarity in viewing Klein's concept of early object love is achieved through tracing some of its historical origins. The author notes that it was inspired by aspects of Ferenczi's theory, hence its similarities with the concept of 'primary love' formulated by another of Ferenczi's analysands, Michael Balint. Ferenczi's thinking on the subject formed part of a broader network of theoretical developments in the history of psychoanalytic ideas. These are shown to have origins in Freud's fluctuations between a 'passive' and a 'genital' characterisation of infantile sexuality. A dialectical tension between these two possibilities, as maintained in the Freudian texts, was partly embodied in the differing outlooks of Klein's two psychoanalysts, Abraham and Ferenczi. The author suggests that it is a mixture of their approaches that partly shaped Klein's thinking on the earliest experiences of love. After outlining these developments the author analyses the nature of early object love as it emerges from Klein's powerful, if intermittent descriptions in the texts. The analysis also tackles a textual ambiguity in Klein's formulations, showing that she explored two kinds of primitive ideal experience without explicitly differentiating them. Such differentiation is important inasmuch as it highlights negative and positive aspects of Kleinian theory at root. PMID- 8491531 TI - Jean Piaget's experiences on the couch: some clues to a mystery. AB - This paper is an attempt to reconstruct the historical, institutional, and personal circumstances leading to and surrounding Jean Piaget's psychoanalysis with Sabina Spielrein. It appears that the young Piaget's interest in psychoanalysis largely emanated from his long-standing problems with his mother. It is suggested that Piaget's lifelong tendency to intellectualise his own emotional experiences may relate to the near omission of affective factors in his psychological theories. PMID- 8491532 TI - The dynamics of reassurance. AB - This paper describes the process of splitting that leads to the establishment of a set of 'versions' of the self and the object, and the relationship between them. The author suggests that the mechanism of reassurance is called into play when a particular anxiety-laden version becomes central, disturbing the patient's psychic equilibrium. The patient then strives to restore the state that he has lost, either in phantasy, or by attempting to draw the analyst into a familiar enactment. A brief description is given of a patient who felt most threatened by the prospect of the analyst being able to think for himself. This challenged more familiar and comforting versions of the two of them involved in the repetitive enactment of earlier object relationships. It is suggested that, paradoxically, the analyst's capacity to make his own observations and judgments invokes for the patient the presence of a third figure, with all the accompanying oedipal anxieties and threats. However, the patient's experience of true reassurance is ultimately derived from his belief that he has not succeeded in replacing the oedipal triangular relationship with one in which he and the analyst are exclusively involved with one another. PMID- 8491533 TI - Knowing and not knowing massive psychic trauma: forms of traumatic memory. AB - It is in the nature of trauma to elude knowledge, both because of deficit and defence. Massive trauma cannot be grasped because there are neither words nor categories of thought adequate to its representation; knowledge of trauma is also fiercely defended against, as it poses a momentous threat to psychic integrity. Yet knowing nevertheless occurs on some level, often in restricted or defensive forms. This paper sets forth various forms of knowing and not knowing massive historical trauma as manifested in clinical symptomatology, transference phenomena, life themes and witnessing narratives. Metaphor is also mentioned as yet another form of knowing and addressing trauma, available primarily to those who have not been directly affected as victims nor as family members of victims. The different forms imply a continuum of progressively more integrated and subjectively owned levels of knowing, directly related to the actual and psychological distance from the traumatic event. Illustrations drawn from clinical and testimonial settings are given for each level of knowing described, and implications for therapeutic strategy are discussed. PMID- 8491534 TI - The bi-logic perception of time. AB - The problem of perception and conceptualisation of time in the unconscious and the conscious is seen in terms of Matte-Blanco's theories. In a short outline of his ideas, symmetrical and asymmetrical logic and his newer concept of 'bi-logic structures' are discussed. Clinical examples from the psychoanalysis of a patient with a time problem are presented to illustrate the hypothesis that a misperception and misconception of time lead in this case to obsessive-compulsive pathology. The clinical application of Matte-Blanco's postulations not only explains the psychopathology of the patient but also allows the formulation of a treatment strategy leading to a positive solution of the problem. PMID- 8491535 TI - The female genital dress-rehearsal: a prospective process at the oedipal threshold. AB - Rather than focus on the girl's phallic identification as a compensatory reaction to her femininity, I offer a conceptual framework through which to examine how the girl symbolically masters and elaborates her biologically unfolding sexuality. Presumably, because her genital inner space can be defined and filled only through the playful retention and expulsion of an external object, the girl's phallic identification paradoxically affords her the first experience of her genital femininity. Borne out of her genital stimulation at the oedipal threshold, the genital dress-rehearsal turns on outside gestures becoming registered as sensations inside her body. As a result of her dual experience, the girl is both phallic and vaginal, giver and receiver, father and mother. Through the magic of play, the girl renegotiates her oath of fidelity to her internal, pre-oedipal mother, while laying claim to the kind of sexual vibrancy that her external, oedipal mother shares with her oedipal father. PMID- 8491536 TI - Personality death, object loss, and the uncanny. AB - The concept of uncanny anxiety can be distinguished from other clinical entities such as anxiety states, depression, or mourning. It has a special relevance to the impact of 'personality death' in which sudden dramatic alterations in psychological function occur. Clinical examples are presented from cases involving neurological trauma and its impact on the beholder. The uncanny experience is composed of, first, a perception that the object is familiar and unfamiliar in an intertwined way; and second, that the object is wooden and dead in a way that strains object constancy. Lastly, a sense of a double, of one person within another, develops in the observer. The uncanny sensation is viewed as a reaction to this doubling. It is a symptom that occurs in reply to the threatened emergence of the unconscious belief that there really are two people there. This belief would be a threat to the ego's soundness. Uncanniness rushes in to protect the ego from feeling attacked by something completely unreal. PMID- 8491537 TI - Latency--a reappraisal. AB - This paper discusses the specific metapsychology and developmental tasks of the latency period. It offers a Kleinian view of the phase and compares it with other current psychoanalytic theories. The emphasis is on the importance of ego and superego growth and integration during latency resulting in better contact with both external and internal reality. Character formation, social integration and learning are discussed as the specific developmental tasks of the period. Freud's original formulation that the latency period is a consequence of the resolution of the Oedipus complex is evaluated in the light of contemporary developments. I draw on the ideas of Klein and others such as Loewald, Burgner, Holder, Tyson to describe it as a process of progressive and more complex elaboration throughout latency, interconnected with superego development. This process of gradual working through is considered to be a fundamental feature of the period. This model of progressive maturation is illustrated with clinical material. The clinical concept of pseudo-latency is used to distinguish between the developmental achievement represented by the establishment of the latency organisation in contrast to a defensive structure (pseudo-latency) which hides pathology. PMID- 8491538 TI - Children and their dreams. AB - The original aim of this report was to present a series of theoretical and technical doubts relating to 'children and their dreams' and the answers I have found. 'From a theoretical viewpoint' shows that although Freud did not investigate repetition compulsion in children's dreams, we can deduce that even children's dreams could not be an exception to repetition. In other words, not all dreams in children are accomplishments of wishes. 'From a technical viewpoint' discusses: (a) the importance psychoanalysts give to children's dreams; (b) ways of bringing and not bringing their dreams to analysis; (c) notes on theory and technique in view of these dreams. PMID- 8491539 TI - Psychosomatic solution or somatic outcome: the man from Burma. Psychotherapy of a case of haemorrhagic rectocolitis. PMID- 8491540 TI - Musical pleasure. AB - Music reactivates foetal experiences of pleasure connected with auditory contact with the mother. Subject to an appropriate setting, the porosity of the skin-ego is increased, permitting bidirectional traffic between inside and outside. Kristeva uses the word significance to denote the meaning occurring along the spectrum from the infralinguistic level (the semiotics of affects) to language. The infralinguistic level (sonic, rhythmic, visual etc. traces) is that on which music develops, music here being presented as the carrier of nebulous 'fantasies' of fusion with the idealised mother of the foetal era. Primitive musical interchanges are illustrated by a clinical vignette. The paper develops the hypothesis that the pleasure of music revives the primitive auditory fusion with the mother; it points out the relations between aesthetics and musical pleasure and between musical forms and the production of pleasure in the unconscious. PMID- 8491541 TI - Measurement of the axial length of cataract eyes by laser Doppler interferometry. AB - PURPOSE: To examine the applicability of the recently developed laser Doppler interferometry technique for measuring the axial length of cataract eyes in a realistic clinical situation. To determine the performance of the instrument as a function of cataract grade. To compare the results to those of ultrasound methods. METHODS: A total of 196 cataract eyes of 100 patients were examined. The axial eye length was determined by laser Doppler interferometry and by two different ultrasound techniques, the applanation technique and the immersion technique. The cataract grade was determined by a commercial instrument that measures backscattered light. RESULTS: Laser Doppler interferometry worked very well except in the cases of the highest cataract grades (4% of the eyes of this study were not measurable because of a too-high lens density). Only 3.5% of the other eyes were not measurable because of fixation problems of the patients. The precision of laser Doppler interferometry is not influenced by the cataract grade (except the highest grade). The standard deviation of the geometric eye length is approximately 20 microns. Linear regression analysis revealed a very good correlation of laser Doppler interferometry and ultrasonic measurements, but a systematic difference was found. The eye lengths measured by laser Doppler interferometry were about 0.18 mm longer than those measured by the immersion technique and about 0.47 mm longer than those measured by the applanation technique. CONCLUSION: These differences are attributed to the laser Doppler interferometry results including the retinal thickness and indentation of the cornea by the applanation technique. The main advantages of the laser Doppler interferometry technique are high precision, high accuracy, and more comfort for the patient because it is a noncontact method, anesthesia is unnecessary, and the risk of corneal infection is avoided. PMID- 8491542 TI - Dynamic visual acuity of normal subjects during vertical optotype and head motion. AB - PURPOSE: To characterize the effect of passive vertical head motion on dynamic visual acuity of young, normally sighted subjects wearing telescopic spectacles, and to relate this to the velocity of images on the retina. METHODS: Static visual acuity was measured without motion. Dynamic visual acuity was measured during vertical, sinusoidal motion of either optotypes or of a servo-driven rotating chair in which subjects were seated. Dynamic visual acuity for head motion was measured unaided, as well as with 1.9X, 4X, and 6X telescopic spectacles. Vertical eye movements were recorded using magnetic search coils. RESULTS: During optotype motion, acuity declined with increasing velocity to a minimum of approximately 20/200 at 100 degrees/sec. Pursuit gain (eye velocity/optotype velocity) for moving optotypes was low except for optotype velocities of 20 degrees/sec of less. Dynamic visual acuity without telescopic spectacles was not sensitive to head motion. Static visual acuity improved with increasing telescopic spectacle power, but dynamic visual acuity became progressively impaired by head motion as telescopic spectacle power was increased. Compared with static visual acuity, head motion with peak velocity of 40 degrees/sec reduced acuity two-fold for 1.9X telescopic spectacles, fourfold for 4X telescopic spectacles, and eightfold for 6X telescopic spectacles. Visual vestibulo-ocular reflex gain with telescopic spectacles increased to values markedly above 1.0, but was always less than telescopic spectacle magnification. There was visual tolerance of slip velocities of 2 degrees/sec or less, above which acuity declined in proportion to the 0.6 power of retinal slip velocity. Above 2 degrees/sec, retinal slip velocity accounted for 95% of the variance in dynamic visual acuity. CONCLUSIONS: These results confirm that acuity is sensitive to retinal image motion in the vertical direction, and extend this finding to indicate that sensitivity of acuity to vertical head motion during wearing of telescopic spectacles is attributable to retinal image slip velocity. PMID- 8491543 TI - Pointwise topographical and longitudinal modeling of the visual field in glaucoma. AB - PURPOSE: To develop a suitable mathematical model for the description of the pointwise distribution of sensitivity across the visual field in glaucoma. METHODS: The pointwise distribution of sensitivity at any given stimulus location for any given examination was described by a joint topographical and longitudinal model. The topographical element modeled the pointwise distribution of sensitivity using a second-order polynomial function in terms of the respective stimulus coordinates whereas the longitudinal element modeled the pointwise distribution of sensitivity using multiple linear regression in terms of the sensitivity at the given location determined at one or more previous examinations. The sample comprised Humphrey Field Analyser (Humphrey Instruments, San Leandro, CA) Program 30-2 and 24-2 fields from 49 patients attending a glaucoma clinic for an average of 3 years. RESULTS: The constant term of the polynomial correlated highly with the mean deviation and moderately with the pattern standard deviation. The goodness-of-fit between the modeled and the measured field increased as an exponential function of the number of previous examinations. The median R2 was 19.6% for the first examination and 83.6% for the sixth examination. The group median optimum percentage of error between the measured and modeled sensitivity at each test location was below 10% (i.e., less than 3 dB), increased with increase in eccentricity, was greater at the extremities of the superior field and varied as a function of the severity of the field loss. CONCLUSION: The model seems to be a promising way to evaluate visual field progression. PMID- 8491544 TI - A feasibility study of 23Na magnetic resonance imaging of human and rabbit vitreal disorders. AB - PURPOSE: To assess the clinical feasibility of sodium magnetic resonance imaging for the visualization and characterization of intraocular tissues. METHODS: 23Na magnetic resonance images were obtained of enucleated human eyes and of rabbit eyes in vivo. The magnetic resonance imaging technique used in this study provided slices of < 2 mm thickness and in-plane resolution of < 2 x 2 mm. From each of these slices local values of spin-spin relaxation time (T2*) were calculated from pixel intensities in each of the eight echoes. RESULTS: The images clearly display normal anatomic details of the lens and vitreous humor, and important pathologic details such as intravitreal and subretinal hemorrhages, ocular melanoma, and retinal detachments. Intraocular tissue identifications based on relative spin-spin relaxation time values and pixel intensities correlate with those made by standard diagnostic techniques. CONCLUSIONS: 23Na magnetic resonance imaging may be used for the visualization and characterization of intraocular tissues. Differentiation among vitreous humor, lens, aqueous humor, subretinal fluid, or hemorrhage and tumor may be based on image intensity and/or spin-spin relaxation times. PMID- 8491545 TI - Analysis of the components of electrically evoked response using a monopolar recording technique. AB - PURPOSE: To assess the significance of the components of the electrically evoked response. METHODS: Twenty-three normal subjects, six patients with macular holes, and three patients with retinal artery occlusion were tested. The electrically evoked responses were recorded from an occipital electrode by applying an electric current of 0.3 mA-2.0 mA with a duration of 5 msec and a frequency of 1.85 Hz. RESULTS: In the normal subjects, three rhythmic waves (N1P1, N2P2, N3P3) were frequently found with fewer individual differences in their latencies than in flash visual evoked potentials. It was found that the amplitude of N1P1 became larger in proportion to the stimulus strength, and that the amplitudes of N2P2 and N3P3 reached their ceiling peaks. The amplitudes of N2P2 were significantly reduced in the affected eyes of patients with a unilateral complete break of the macula and branch retinal artery occlusion including the macular area. Conversely, in one patient with central retinal artery occlusion, whose visual acuity was good because the cilioretinal artery was patent, the amplitude of N1P1 was significantly reduced in the affected eye. CONCLUSIONS: N2P2 in electrically evoked response might originate mainly in the macular area. The analysis of N2P2 may be useful for further clinical applications of electrically evoked response. PMID- 8491546 TI - Lipopolysaccharide in adherence of Pseudomonas aeruginosa to the cornea and contact lenses. AB - PURPOSE: To determine the role of smooth or rough lipopolysaccharide on adherence of Pseudomonas aeruginosa bacteria to the rat cornea in vitro and on contact lenses of differing types. METHODS: Adherence of a smooth (AK957) and isogenic rough strain (AK1012) of P. aeruginosa bacteria to rat corneas that were either normal, traumatized using a 20-gauge needle or treated for 15 min with 0.1N sodium hydrochloric acid was assessed by homogenization and viable counting. Adherence of these organisms to 43 unworn contact lenses representing the four Food and Drug Administration lens groups was also assessed using viable counts. RESULTS: Attachment to contact lenses was greater for the smooth strain for all four lens types (P < 0.001). No variation in adherence to the different lens types was observed. Smooth bacteria also adhered to the cornea to a greater extent than the rough strain, regardless of trauma type (P < 0.001). Adherence to traumatized corneas was greater than to nontraumatized corneas for both strains of P. aeruginosa bacteria (P < 0.01). Measurement of surface hydrophobicity of the two bacterial strains revealed that the smooth strain was more hydrophobic than the rough strain (P < 0.001), perhaps accounting for the adherence pattern. CONCLUSIONS: These results indicate that bacterial surface characteristics may be important determinants of adherence and could explain the propensity of certain bacterial strains to infect the cornea. PMID- 8491547 TI - The role of contact lenses, trauma, and Langerhans cells in a Chinese hamster model of Acanthamoeba keratitis. AB - PURPOSE: To determine the role of contact lenses, corneal trauma, and Langerhans cells in the development of keratitis caused by Acanthamoeba organisms in Chinese hamsters. METHODS: Various methods were used to induce corneal infections in Chinese hamsters, including application of parasite-laden contact lenses. The role of corneal epithelial defects in promoting parasite binding was examined in vitro in a microscopic binding assay. The role of corneal abrasion in the development of Acanthamoeba keratitis was also examined in Chinese hamsters exposed to parasite-laden contact lenses. Other experiments evaluated the effect of infiltrating Langerhans cells on the incidence and severity of Acanthamoeba keratitis. RESULTS: Corneal epithelial defects promoted extensive parasite binding to abraded corneas compared to intact, nonabraded counterparts. Corneal abrasion was absolutely necessary for the induction of Acanthamoeba keratitis in hamsters infected with contaminated contact lenses. Infection was never detected unless the corneas were abraded before exposure to parasite-laden contact lenses. The presence of Langerhans cells in corneas prevented the development of Acanthamoeba keratitis. CONCLUSIONS: The highest incidence of Acanthamoeba keratitis occurs in corneas expressing epithelial defects and exposed to parasite laden contact lenses. The presence of Langerhans cells in corneas exposed to parasite-laden contact lenses prevents the development of Acanthamoeba keratitis. PMID- 8491548 TI - Cleavage and activation of corneal matrix metalloproteases by Pseudomonas aeruginosa proteases. AB - PURPOSE: To examine the effect of Pseudomonas aeruginosa on the expression of corneal matrix metalloproteases and the effect of its proteases on activation of corneal matrix metalloproteases in vitro. METHODS: Rat corneas and human corneal fibroblasts were co-cultivated with two different strains (RPS & 599A) of P. aeruginosa and one strain of Staphylococcus aureus, and the conditioned media were analyzed for proteolytic activity by gelatin and casein zymography. Human corneal fibroblast-conditioned medium was incubated with that from either strain of P. aeruginosa and was analyzed in a similar manner. RESULTS: Normal rat corneas in organ culture produce a 65 kDa gelatinase (inactive matrix metalloprotease-2), whereas thermally injured rat corneas additionally produce gelatinases with molecular masses of 92 kDa (inactive matrix metalloproteases-9) and > 200 kDa. Matrix metalloprotease-2 is also detected in human corneal fibroblast-conditioned medium. Although these matrix metalloproteases are no longer detectable when rat corneas or human corneal fibroblasts are co-cultured with two strains of P. aeruginosa for 48 hr, a 58 kDa gelatinase fragment appears in earlier stages of co-culture. In contrast, S. aureus does not affect matrix metalloprotease-2. The 58 kDa fragment is also evident by incubating human corneal fibroblast-conditioned medium with that from either strain of P. aeruginosa. Conditioned medium from the RPS strain, which produces both elastase and alkaline protease, is more effective in cleaving matrix metalloprotease-2 than that from the 599A strain, which expresses mainly alkaline protease. CONCLUSION: The secreted inactive corneal matrix metalloprotease-2 is activated through limited proteolysis by pseudomonal proteases. PMID- 8491549 TI - Growth factors modulate clonal growth and differentiation of cultured rabbit limbal and corneal epithelium. AB - PURPOSE: To compare the extent of modulation by various growth factors on clonal growth and differentiation between corneal and stem cell-containing limbal epithelium. METHODS: A reported serum-free clonal growth assay was used. The mitogenic response was measured by colony forming efficiency, colony size, and bromodeoxyuridine labelling index; the differentiation was assessed by AE-5 monoclonal antibody staining. RESULTS: As compared to controls in an insulin containing basic medium, the addition of epidermal growth factor, acidic fibroblast growth factor, basic fibroblast growth factor, and a high dose of nerve growth factor was mitogenic for both epithelia. Cholera toxin was also mitogenic, but platelet-derived growth factor might not have, and insulin-like growth factor type I lacked an additive mitogenic effect with insulin. The mitogenic effect of epidermal growth factor differed from the others in its dose dependent down-regulation and in having more migratory cells in epidermal growth factor-stimulated colonies. In contrast to these mitogens, transforming growth factor-beta 1 exhibited a clear inhibitory effect in the controls as well as in epidermal growth factor- or fibroblast growth factor-stimulated cultures. Transforming growth factor-beta 1's inhibitory effect was correlated with strong AE-5 staining, whereas the mitogenic effect of epidermal growth factors, fibroblast growth factors or nerve growth factors was correlated with the presence of negative AE-5 colonies. CONCLUSION: There exist potential dynamic interactions among various growth-modifying cytokines in controlling epithelial growth and differentiation. The lack of specific activation of limbal stem cells in this culture assay also suggests that other unidentified factor(s) might be regulating stem cell functions. PMID- 8491550 TI - Bright environmental light accelerates rhodopsin depletion in retinoid-deprived rats. AB - PURPOSE: Dietary deficiency in the retinoid precursors of the visual pigment chromophore 11-cis retinal eventually results in selective degeneration of the photoreceptor cells of the vertebrate retina. An early effect of retinoid deficiency is depletion of chromophore from the photoreceptor outer segments. Experiments were conducted to determine whether the rate of chromophore depletion was affected by the intensity of environmental light. METHODS: Rats were maintained on diets either containing or lacking retinoid precursors of 11-cis retinal for up to 30 weeks. Animals in both dietary groups were exposed to either bright (90 lux) or dim (5 lux) cyclic light for the duration of the experiment. At various time intervals retinal rhodopsin content and photoreceptor densities were determined in animals from each treatment group. RESULTS: Bright light greatly accelerated the depletion of rhodopsin from the retina. Rhodopsin was almost completely depleted from the retinas of the retinoid-deficient animals raised under bright light for 25 weeks, whereas the dim-light-reared animals fed the retinoid-deficient diet still had significant amounts of retinal rhodopsin even after 30 weeks. Bright light alone moderately depressed retinal rhodopsin levels in animals fed the diet containing a vitamin A precursor of 11-cis retinal. Among rats fed the latter diet, retinal rhodopsin content in the animals kept in bright cyclic light was maintained throughout the experiment at about 70% of the amount of rhodopsin in rats housed in dim cyclic light. The light-related rhodopsin depletion in the retinoid-deprived rats was accompanied by photoreceptor cell death. After 30 weeks of treatment, photoreceptor cell densities remained similar in all treatment groups except the retinoid-deprived group housed under bright cyclic light. In the latter group, photoreceptor cell densities in the central retinas were reduced by an average of more than 50% after 30 weeks. Retinoid deficiency and bright light exposure alone each resulted in a reduction in rod outer segment size. An even greater reduction in outer segment size was observed in vitamin A-deprived animals housed under bright cyclic light. CONCLUSION: These findings indicate that light accelerates the depletion of retinoids from the retina and the accompanying photoreceptor cell degeneration. PMID- 8491551 TI - Effects of intravenous iodoacetate and iodate on pH outside rod photoreceptors in the cat retina. AB - PURPOSE: Effects of intravenous iodoacetate (a glycolysis inhibitor) and iodate (a metabolism inhibitor selective to retinal pigment epithelium) on light-evoked alkalinizations and hypoxia-induced acidifications were studied in the dark adapted cat retina, in vivo, to learn about pH regulation. METHODS: pH was recorded in the extracellular space surrounding rod photoreceptors with double barrelled H(+)-selective microelectrodes. RESULTS: Intravenous infusion of 5 mg/kg iodoacetate-induced alkalinizations in the outer nuclear layer and suppressed both light-evoked and hypoxia-induced pH responses immediately. Iodate injection (30 mg/kg) produced acidifications in the subretinal space and affected light-evoked alkalinizations gradually but not hypoxia-induced acidifications. CONCLUSIONS: These results suggest that rods glycolysis plays an important role in both light-evoked and hypoxia-induced pH responses. And the retinal pigment epithelium may have little concern with light-evoked alkalinizations except that it plays an important role in regenerating the rhodopsin to be needed for the light responses of photoreceptors. Furthermore, the finding of the intravenous iodoacetate-induced alkalinization in the outer nuclear layer supports that acid production by rods in the dark is originated from glycolysis to support the dark current. The iodate-induced acidification in the subretinal space indicators that the retinal pigment epithelium might actively transport acids from the subretinal space to the choroid. PMID- 8491552 TI - Protection of rabbit retina from ischemic injury by superoxide dismutase and catalase. AB - PURPOSE: To provide evidence that free radical damage is a component of postischemic retinal injury; to determine whether antioxidant enzymes, superoxide dismutase (SOD) and catalase, can protect the retina from ischemic injury. METHODS: Total retinal ischemia for 60 or 75 min was produced in Dutch rabbits by raising intraocular pressure. Retinal recovery was monitored with the electroretinogram. Enzymes were administered as an intravenous bolus dose 2-3 min before restoration of circulation. RESULTS: In eyes subjected to 60 min ischemia, the amplitude of the a-wave 4 hours after reperfusion averaged 114.9% of baseline value in control rabbits and 126.5% in SOD-treated animals. The b-wave amplitude at this time was 79.3% and 106.8% in control rabbits and SOD-treated rabbits, respectively. After an ischemic insult of 75 min, at 4 hours the a-wave amplitude was 89.2% of baseline in control eyes, 108.8% in SOD-treated eyes, 159.6% in eyes that received a combination of SOD and catalase, and 149.8% in catalase-treated eyes. The amplitude of the b-wave was reduced to 47.8% in control eyes and 44.8% in SOD-treated eyes, but recovered to 92.3% in rabbits that received the combination therapy and 98.8% in animals that received catalase alone. CONCLUSIONS: These findings suggest that free radical generation is involved in ischemic tissue damage. The fact that antioxidant enzymes can be protective has implications for the treatment of acute ischemic diseases of the retina. PMID- 8491553 TI - Stereochemistry of the human macular carotenoids. AB - PURPOSE: To complete identification of the major components of the human macular pigment. METHODS: Chemical ionization mass spectra of the macular pigment components were obtained and compared with those of zeaxanthin and lutein standards. A comparison was also made using chiral column high-performance liquid chromatography, which is capable of resolving individual stereoisomers of these carotenoids. Zeaxanthin and lutein from human blood plasma were similarly analyzed. RESULTS: The mass spectrometry data supported earlier work in which high-performance liquid chromatography, UV-visible spectrometry and chemical modification showed that the macular pigment comprises two carotenoids with identical properties to those of zeaxanthin and lutein. Chiral column chromatography showed that the "zeaxanthin" fraction is a mixture of two stereoisomers, zeaxanthin itself [(3R,3'R)-beta,beta-Carotene-3,3'-diol] and meso zeaxanthin [(3R,3'S)-beta,beta-Carotene-3,3'-diol]. The other fraction is the single stereoisomer, lutein [(3R,3'R,6'R)-beta,epsilon-Carotene-3,3'-diol]. In human blood plasma, only zeaxanthin and lutein were found. CONCLUSIONS: The results strongly suggest that meso-zeaxanthin results from chemical processes within the retina. Noting that lutein exceeds zeaxanthin in plasma but that the combined zeaxanthin stereoisomers exceed lutein in the retina, the possibility was considered that meso-zeaxanthin is a conversion product derived from retinal lutein. Under nonphysiologic conditions, the authors demonstrate that a base catalyzed conversion of lutein to zeaxanthin yields only the meso-(3R,3'S) stereoisomer. PMID- 8491554 TI - Modulation of plasminogen activator inhibitor-1 and urokinase in retinal pigmented epithelial cells. AB - PURPOSE: To examine the effect of several agents that either stimulate or inhibit neovascularization on plasminogen activator inhibitor-1 and urokinase in retinal pigmented epithelial cells and vascular endothelial cells. METHODS: Steady-state levels of messenger RNA were assessed by Northern blots and dot blots and protein levels were assessed by immunoprecipitation. RESULTS: Data indicate that messenger RNA levels for plasminogen activator inhibitor-1 are modulated in similar fashion in both cells types, being increased by incubation with transforming growth factor-beta, dexamethasone, tumor necrosis factor, phorbol myristate acetate, and thrombin. Levels of urokinase messenger RNA in retinal pigmented epithelial cells are significantly increased only by phorbol myristate acetate and are decreased by dexamethasone and transforming growth factor-beta, whereas in endothelial cells plasminogen activator urokinase messenger RNA is increased by each of the stimuli except dexamethasone, which causes a decrease. Immunoprecipitation experiments demonstrate similar modulation of inhibitor-1 proteins secreted by retinal pigmented epithelial cells, whereas urokinase is difficult to detect. CONCLUSIONS: These data suggest that retinal pigmented epithelial cells may help to alter proteolytic activity in the subretinal space and thereby participate, along with endothelial cells, in the regulation of choroidal neovascularization. PMID- 8491555 TI - Retinoids increase urokinase-type plasminogen activator production by human retinal pigment epithelial cells in culture. AB - PURPOSE: To examine the effect of two retinoids, all-trans-retinoic acid (tretinoin) and all-trans-9-(4-methoxy-2,3,6- trimethylphenyl)-3,7-dimethyl- 2,4,6,8-nonatetraenoic acid (acitretin) on the production of plasminogen activators and plasminogen activator inhibitors by human retinal pigment epithelial cells in culture. METHODS: Cultures of human retinal pigment epithelial cells were incubated with either of the retinoids at a concentration of 1 microM for 24-72 hours. The media were assayed using solid-phase immunocapture assays and zymography. RESULTS: Both retinoids caused a twofold to sevenfold increase in urokinase-type plasminogen activator in the medium. The effect was seen after 24 hours in culture and was further augmented up to 72 hours. No significant amounts of tissue-type plasminogen activator were detected. The plasminogen activator inhibitor activity was unaffected by the retinoids. Proliferation and morphology of retinal pigment epithelial cells were also unaffected by the retinoids in incubations for up to 72 hours. CONCLUSIONS: Retinoids profoundly affect the extracellular proteolysis of retinal pigment epithelial cells in culture. This effect may be related to the differentiation inducing activity of retinoids seen in other cell types, often connected with changes in extracellular proteolysis. It is possible that retinoids may modulate dedifferentiation, proliferation, and migration of retinal pigment epithelial cells seen in vitro, as well as in the pathogenesis of retinal disease. PMID- 8491556 TI - Synergistic suppression of retinal pigment epithelial cell proliferation in culture by radiation and hyperthermia. AB - PURPOSE: To study combination effects of radiation and hyperthermia on the in vitro cell proliferation of cultured human retinal pigment epithelial cells; to explore possible application of the combination treatment for proliferative vitreoretinopathy. METHOD: Cultured human retinal pigment epithelial cells were treated by radiation, hyperthermia, or a combination of the two. Cell proliferation was evaluated by counting the cell number and by the uptake of bromodeoxyuridine. RESULTS: X-ray irradiation of 100 cGy or 300 cGy was not effective in suppressing proliferation of the retinal pigment epithelial cells. Similarly, heat treatment at 42 degrees C or 43 degrees C for 30 min did not suppress proliferation of the retinal pigment epithelial cells. However, combination of hyperthermia at 42 degrees C for 30 min with 300 cGy irradiation suppressed cellular growth of the retinal pigment epithelial cells to 35.7% of the control as estimated by the cell counting and to 48.3% by bromodeoxyuridine uptake study. Combination treatment of 43 degrees C, 30 min hyperthermia and 300 cGy irradiation was more effective. CONCLUSIONS: A combination of low-dose radiation and mild hyperthermia is effective in the suppression of growth of cultured human retinal pigment epithelial cells, and the effects were found to be synergistic. It is expected that the synergistic effects will lower the radiation dose and also reduce the possible side effects of radiation in the treatment of proliferative vitreoretinopathy. PMID- 8491557 TI - Oxygen dependency of retinal adhesion. AB - PURPOSE: Normal retina is firmly attached to the retinal pigment epithelium, but the force of this adhesion drops precipitously within the first 2-3 min after enucleation. The purpose was to study metabolic factors that might be relevant to this postmortem failure of adhesion. METHODS: Dutch rabbit retina was manually peeled from the retinal pigment epithelium on strips of enucleated eyecup within a 37 degrees C bath. Retinal adhesiveness was measured by observing the amount of retinal pigment epithelium that remained adherent to the retina. RESULTS: Autologous whole blood in place of salt solution retarded the decrease in adhesiveness. A solution of hemoglobin alone was similarly effective, whereas methemoglobin solution failed to help the persistence of retinal adhesion. Bubbling oxygen into the salt solution and circulating it to avoid oxygen depletion at the tissue boundary also proved effective at sustaining retinal adhesiveness. Eyes made ischemic in vivo for 5 min or longer, by elevating intraocular pressure, showed virtually no retinal adhesion when enucleated immediately thereafter. However, eyes made ischemic for 10 min, but allowed to regain circulation for 5 min before enucleation, showed a return of retinal adhesiveness to 80% of normal. CONCLUSIONS: Oxidative metabolism is critical to the maintenance of retinal adhesiveness, and the effects of oxygen deprivation on adhesion are reversible within a certain time period. PMID- 8491558 TI - Evidence from human electroretinogram A and off responses that color processing occurs in the cones. AB - PURPOSE: To investigate two apparent anomalies of the human electroretinogram: the "on" and "off" components of the cone based PIII are unequally sized, and transitions from red to green, which are electroretinographically silent, yield reverse transitions (green to red) in which a-waves develop. METHODS: Ganzfeld electroretinograms were obtained with intense 100 msec flickering flashes from red and green light-emitting diode. Such stimuli light-adapt the retina, and the responses are caused by the excitation of long and medium wavelength cones. RESULTS: In the 10-20 msec after the beginning of a flash (black to green or black to red) the beginning of rapid receptor-generated a-wave is seen. Ten to twenty milliseconds after the end of the flash, the beginning of a rapid positive going off response, also derived from receptors can be seen. If the retina is stimulated by the abrupt change from one wavelength of light to another (eg, from "green" to "red"), at times > 20 msec after the change there are always slow changes in potential (presumably caused by postsynaptic activity) regardless of the relative intensities of red and green. However, if the two light intensities are adjusted appropriately, 10-20 msec after the transition from green to red no electroretinographic a-wave (or off response) develops--the transition is "silent." When the transition reverses (changes back from red to green), an a wave occurs. In the same way if a red-to-green transition is made silent by altering the relative light intensities, the green-to-red reversal evokes an a wave. This occurs for numerous pairs of red and green intensities. Rod intrusion or minor electroretinogram components do not explain this result. The relative red:green intensity in two color-anomalous subjects is different to that in three normal subjects. The rule for a silent transition is that the decrease in excitation in one cone type should be twice the increase in excitation in the second cone type. CONCLUSIONS: The most likely cause is a reduction in the amplitude of cone receptor potentials 20-50 msec after the onset of the stimulus, caused by a sign-reversing feedback mechanism such as that described in amphibians. This implies that the chromatic signals for color vision required by theorists are partly generated in the cones. PMID- 8491559 TI - Islet transplantation inhibits diabetic retinopathy in the sucrose-fed diabetic Cohen rat. AB - PURPOSE: To study the effect of islet transplantation on the development of diabetic retinopathy in the sucrose-fed diabetic Cohen rat, a useful experimental model of accelerated microvascular disease. METHODS: Syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection was performed either after 6 weeks or after 12 weeks of diabetes, i.e., before or after the first morphologic retinal changes, respectively. Retinal digest preparations were examined using quantitative morphologic parameters. RESULTS: After 26 weeks of diabetes, characteristic features of background retinopathy such as a 5% increase in capillary endothelial cells, a 27% pericyte dropout, acellular occluded vessels and, occasionally, microaneurysms developed in untreated animals. Islet transplantation performed after 6 weeks of diabetes completely prevented endothelial cell proliferation and diminished pericyte loss (2950 +/- 140 vs 2390 +/- 40 in diabetic controls, P < 0.01). A significant increase in acellular occluded capillaries persisted (31 +/- 14 vs 8 +/- 2 in NC; P < 0.01). Islet transplantation after 12 weeks of diabetes, i.e., after established pericyte loss, only partially restored capillary cell composition and did not prevent retinal vessel occlusion. These findings indicate that the beneficial effect of islet transplantation on diabetic retinopathy is limited to a time very early in the evolution of this process. CONCLUSIONS: These data suggest that irreversible changes induced by antecedent hyperglycemia play a central role in the progressive development of diabetic retinopathy. PMID- 8491560 TI - Novel procedures for isolating intact retinal vascular beds from diabetic humans and animal models. AB - PURPOSE: To improve the 30-year-old "trypsin digestion" procedure for isolation of the complete retinal vasculature, which, in its time, was a revolutionary advance that allowed important discoveries about diabetic retinopathy; to provide a method that will yield more consistent results when applied to retinas representing a wide range of ages, species, and severity of vascular disease, such as that occurring in diabetes. METHODS: Because the Difco trypsin preparation (Difco Laboratories, Detroit, MI) is a crude pancreatic extract, containing variable amounts of chymotrypsin, elastase, amylase, lipase, ribonuclease, collagenase, and other contaminants, an attempt was made to determine which of the major enzymes alone (using purified preparations), or what combination of enzymes, might be most effective in providing consistently clean yet intact retinal vasculatures from eyes of different origins. RESULTS: Purified elastase alone (40 U/ml) in 100 mmol/l sodium phosphate buffer with 150 mmol/l sodium chloride and 5 mmol/l EDTA at pH 6.5 and 37 degrees C gave better results than various concentrations of purified trypsin or chymotrypsin alone, or mixtures of trypsin/chymotrypsin, trypsin/elastase, chymotrypsin/elastase, or the crude trypsin preparation. CONCLUSIONS: Elastase, which exhibits broad protease activity, and not trypsin, is the most important enzyme of the standard, crude trypsin digestion procedure for removal of the nonvascular tissues of the retina. PMID- 8491561 TI - Stimulation of DNA synthesis and c-fos expression in corneal endothelium by insulin or insulin-like growth factor-I. AB - PURPOSE: To study the growth regulation of bovine corneal endothelium, the effects of insulin and insulin-like growth factor-I on the expression of the c fos proto-oncogene as well as on DNA synthesis were analyzed. Bovine corneal endothelial cells were also analyzed for the presence of insulin and insulin-like growth factor-I receptors. METHODS: Indirect immunofluorescence was used to assess the effect of stimulation by insulin and insulin-like growth factor-I on c fos protein expression and DNA synthesis quiescent bovine corneal endothelium. Receptor number was determined by 125I-insulin or 125I-IGF-I binding studies. RESULTS: Fetal bovine serum strongly stimulated c-fos protein expression and DNA synthesis. Insulin-like growth factor-I was less effective while insulin was effective only at high concentrations. Scatchard analysis of 125I-insulin-like growth factor-I and 125I-insulin binding to bovine corneal endothelium revealed 180,000 IGF-I receptors and 7,000 insulin receptors. CONCLUSION: The number of insulin-like growth factor-I receptors far exceeds the number of insulin receptors in bovine corneal endothelium, suggesting that the effects of insulin on c-fos gene expression and mitogenesis were likely to be mediated through the insulin-like growth factor-I receptor. PMID- 8491562 TI - Lens regeneration in New Zealand albino rabbits after endocapsular cataract extraction. AB - PURPOSE: To evaluate the regenerative capacity of the adult rabbit lens after removal of a Concanavalin A-induced posterior subcapsular cataract. METHODS: Cataractogenesis was induced by intravitreal injection of Concanavalin A in adult New Zealand albino rabbits. At 7 mo postinjection, the cataracts were removed. Endocapsular lens extraction was performed by phacoemulsification and irrigation/aspiration with Balanced Salt Solution. RESULTS: Postoperatively, lens regeneration was first noted in the Balanced Salt Solution normal lens group at 3 weeks and the Concanavalin A cataract group at 6 weeks. By the 3-mo postoperative examination, lens regrowth, measured by digital image analysis, filled 74.5% of the capsule bag in the Balanced Salt Solution normal lens group and 46.6% in the Concanavalin A cataract group. In the latter group, less lens material was regenerated and at a slower rate than in eyes with extraction of a normal lens. CONCLUSION: This experimental model is the first to show that lens regeneration can occur after removal of cataracts secondary to inflammation. PMID- 8491563 TI - Site-dependent distribution of macrophages in normal human extraocular muscles. AB - PURPOSE: Clinical data indicate that extraocular muscles have different susceptibilities for some orbital immune disorders depending on their anatomic location. The resident immunocompetent cells may be important mediators in the local pathogenesis of such disorders so the distribution of these cells was studied in extraocular muscles obtained from normal human donors. For comparison skeletal muscles were studied. METHODS: The cell distributions were analyzed quantitatively in cryostat cross-sections subjected to a two-step immunoperoxidase method using monoclonal antibodies against T cells, B cells, macrophages and several other markers for cell differentiation or activation. The macrophage distribution was analyzed in more detail using on-line semiautomatic image analysis equipment (VIDAS, Kontron, Elektronik GmbH, Eching, Germany). RESULTS: Extraocular muscles contain numerous macrophages, fewer human leukocyte antigenD-related (HLA-DR) positive cells and T cells, whereas B cells are absent. The numeric density of all cell types, and macrophages in particular, is much higher in extraocular muscles than in skeletal muscles. In extraocular muscles the majority of T cells are positive for the CD8 antigen (suppressor/cytotoxic), in skeletal muscle CD4 positive T cells (helper) predominate. CONCLUSIONS: Extraocular muscles contain many more CD8-positive cells and macrophages per square millimeter than skeletal muscles. Of all the cell types studied, only the macrophage distribution differs significantly among the normal extraocular muscles: the medial and inferior recti muscles contain about twice as many macrophages as the lateral rectus and superior oblique muscles. Their mean sizes (area) or shape distributions however, appear to be similar. PMID- 8491564 TI - Senile cataract progression studies using the Lens Opacities Classification System II. AB - PURPOSE: To determine cataract progression rates at 6-mo intervals as evaluated using the Lens Opacities Classification System II (LOCS II). METHODS: Idiopathic age-related cataracts in both eyes of 50 cataract patients and 17 normal control subjects were graded. The lenses were reexamined at 6 and 12 mo (+/- 2 mo) from baseline to determine rates of change. Progression or regression in patients or control subjects was considered to have occurred at the 6-mo examination if a one or more step change in the LOCS II grading was noted in at least one eye at 6 mo and maintained at the 12-mo visit. RESULTS: Six months from baseline, 38% of patients' conditions worsened in the nuclear area, 34% of patients' conditions worsened in the cortical region, and 8% of patients' conditions worsened in the posterior subcapsular region. Regression rates were 4% in each region. The percentages of patients progressing in the nuclear and cortical regions were significantly greater than the corresponding regression rates (P < .001). Greater progression was noted in the nuclear (P = .06) and posterior subcapsular (P < .01) regions in patients with early opacities (LOCS + 1/+2) as compared to patients with no opacities initially in the same lenticular areas. CONCLUSION: This study suggests that the LOCS II is capable of detecting changes in lens opacities in a relatively short period of time among persons with early to moderate opacities. PMID- 8491565 TI - Retinal pigment epithelial cell transplants in retinal degeneration slow mice do not rescue photoreceptor cells. AB - PURPOSE: To determine if retinal pigment epithelial cells are in any way involved in the degeneration of photoreceptor cells in the retinal dystrophy mouse model, retinal degeneration slow (rds); to determine if normal retinal pigment epithelial cell transplants can affect outer segment development in the retina. METHODS: Retinal pigment epithelial cells of neonatal normal pigmented C3H mice were isolated and transplanted into retinas of postnatal day 33 albino rds mice. Then eyes of 4-month-old rds mice, retinal pigment epithelial cell-transplanted and sham and non-treated control mice, were processed for light and electron microscopy and the thickness of the outer nuclear layer were measured and compared. RESULTS: Measurements of outer nuclear layer thickness in the transplant and control groups revealed that normal retinal pigment epithelial cell transplants did not cause photoreceptor cell rescue in rds mice. In addition, outer segments were not seen in retinal pigment epithelial cell transplanted rds retinas. CONCLUSIONS: This study supports the conclusions of other investigators that the photoreceptor cell is the primary site of the genetic defect that results in retinal dystrophy in the rds mouse model. PMID- 8491566 TI - Acetylated alpha-tubulin in the connecting cilium of developing rat photoreceptors. AB - PURPOSE: To examine the distribution of acetylated alpha-tubulin in the connecting cilium of rat rod photoreceptors during different stages of photoreceptor development. METHODS: An antibody found to be specific for the acetylated form of alpha-tubulin was used in immunoelectron microscopy of retinas from animals of different ages. RESULTS: All the microtubules of the connecting cilium, including those of the basal bodies, were found to contain acetylated alpha-tubulin at the earliest stage of outer segment development, before the cilium has begun to grow out from the cell, and at all subsequent stages. CONCLUSIONS: These results indicate that the alpha-tubulin of the connecting cilium is acetylated either before, or at least very soon after, its assembly into microtubules. Given that acetylation of alpha-tubulin is correlated with stable microtubules, the results suggest that stable microtubules might be important in creating the foundation for the formation of the outer segment, as well as in helping maintain the polarity of the mature photoreceptor. PMID- 8491567 TI - Cytokine production by mononuclear cells from patients with chronic renal failure. AB - The interleukins play a central role in the regulation of the immune system function. In the present study we compared the ability of peripheral blood mononuclear cells (PBMC) from three groups of uremic patients and 15 healthy controls to release interleukin-2 (IL-2) and interleukin-3-like activity (IL-3 LA). In the first group, 11 patients with chronic renal failure (CRF) not yet on dialysis treatment, IL-2 and IL-3-LA were similar to those of the controls. The finding of an increased IL-2 activity in the CRF group suggests that factors other than membrane blood interactions are involved in its production. In the second group, 15 patients on hemodialysis (HD), Il-2 activity measured pre-HD was higher than in the control group (P < 0.005) but decreased slightly post-HD; and IL-3-LA pre-HD was higher than in the controls but decreased post-HD. The pre-HD high levels of IL-2 and IL-3-LA support the role of membrane blood interactions in inducing cytokine activity. In the third group, 13 patients on continuous ambulatory peritoneal dialysis (CAPD), IL-2 and IL-3-LA were similar to the controls. The normal values found in the CAPD group suggest that this modality of dialysis leads to a more normal cytokine production and thus may prevent complications observed in acute and chronic hemodialysis. PMID- 8491568 TI - Abnormal thallium stress test and normal coronary angiograms: catheterization and clinical characteristics. AB - Left ventricular end-diastolic pressure at rest, left ventricular ejection fraction, thallium segmental abnormalities, as well as sex, age and presence of diabetes mellitus, hypertension, hypercholesterolemia and smoking excess were analyzed in 40 patients with abnormal thallium stress test and normal coronary angiograms. Of these patients, 25 had elevated left ventricular end-diastolic pressure and "low normal" ejection fraction (group 1), while the other 15 had normal left ventricular end-diastolic pressure and "high normal" ejection fraction (group 2). The left ventricular end-diastolic pressure was 18.1 +/- 4.5 mm Hg in group 1 vs. 8.5 +/- 2.4 mm Hg in group 2 (P < 0.000). The ejection fraction was 57.6 +/- 8.3% in group 1 vs. 63.9 +/- 9.1% in group 2 (P < 0.05). There was no difference between the groups in relation to the abnormal segment on thallium stress tests, aged and sex. Although the number of patients was too small for meaningful statistical analysis, most of the patients with diabetes mellitus, hypertension, hypercholesterolemia or smoking history were in group 1. Thus, the patient population with abnormal results on radionuclide exercise tests and angiographically normal coronary arteries probably comprises two groups: a) patients with decreased diastolic and relatively decreased systolic performances which might reflect coronary flow disturbances, and b) patients with normal diastolic and systolic performances, probably reflecting "true false positive thallium stress test". PMID- 8491569 TI - Essential thrombocythemia: a relative benign long-term course. AB - The disease manifestations, response to therapy, and follow-up course of 35 patients with essential thrombocythemia seen in a single center were evaluated. The median age was 53 years (range 17-81). Twelve patients were asymptomatic on presentation and the diagnosis was incidental. Twenty-three patients presented with thrombocytosis-related symptoms, most commonly neurological, microcirculatory, or thromboembolic. In no patient did hemorrhage occur as a presenting symptom. The mean platelet count (+/- SD) at diagnosis was 858 +/- 223 x 10(9)/l and the mean maximal count during the follow-up period was 989 +/- 269 x 10(9)/l. The median follow-up of the entire group was 54 months (range 12-172). Ten of the 12 patients who were asymptomatic on presentation remained so during the observation period, while 10 patients who presented with thrombocytosis related symptoms became asymptomatic following a single course of treatment with no recurrence of symptoms. Thirty of the 35 patients were treated with busulfan or hydroxyurea or both. Response to cytoreductive therapy was prompt and continuous in most patients. Essential thrombocythemia might be a disease of grave consequence but it seems that in general its course under treatment is more benign than previously thought. PMID- 8491570 TI - Antimicrobial resistance of urinary isolates in the community and its relation to antibiotic use. PMID- 8491571 TI - Changing prevalence of iron deficiency anemia in infants of the Haifa subdistrict. PMID- 8491572 TI - Ischemic colitis complicating AA amyloidosis and familial Mediterranean fever. PMID- 8491573 TI - Hemolysis following transfusion of erythrocytes from a donor with G6PD deficiency and beta-thalassemia minor. PMID- 8491574 TI - Serum concentration of orally administered gentamicin in infants with diarrhea. PMID- 8491575 TI - Filariasis caused by Loa loa in an Israeli temporary resident of west Africa. PMID- 8491576 TI - Life events readjustment scale in a kibbutz. PMID- 8491577 TI - Syndrome X: understanding and evaluating the patient with chest pain and normal coronary arteriogram. PMID- 8491578 TI - Role of lipids in the progression of renal disease in chronic renal failure: evidence from animal studies and pathogenesis. AB - The purpose of this review has been to summarize the effects of lipids on the progression of renal disease in chronic renal failure. Animal studies show that hypercholesterolemia as induced by a high cholesterol diet can aggravate the progression of renal disease in experimental models of chronic renal failure. Hypolipidemic treatment, when given to animals with chronic nephropathy associated with endogenous hyperlipidemia such as in reduced renal mass, obese Zucker rat, PAN nephrosis and the Dahl salt-sensitive rat, results in a reduction in serum lipids levels concomitant with a decrease in the renal damage. Enrichment of the diet with omega-6 PUFA given to rats with reduced kidney mass leads to a reduction in renal damage, probably due to beneficial changes in renal fatty acid composition, while supplementation of a fish oil diet to rats with immune complex nephritis resulted in a similar beneficial effect, probably due to a suppression in the local immunologic processes. The pathogenesis of this effect is still only partially understood. Lipid deposition and oxidation in the renal mesangium, migration of circulatory monocytes into the renal mesangium and their transformation to foam cell, and alterations in renal PUFA metabolism and composition are the main known alterations that accompany lipid-induced renal damage. These alterations, which are similar to those observed in atherosclerosis, lead to alterations in the normal biologic processes in the renal mesangium and terminate in glomerulosclerosis. Extrapolating the data from experimental studies to human renal diseases, it may be assumed that lipid metabolism has a significant impact on the gravity and progression of renal disease in a selected patient population, namely in patients with chronic renal disease. If so, hypolipidemic treatment or administration of certain types of PUFA can be important in the prevention of progression of the renal disease in these patients. Clinical studies are needed to elucidate this issue. PMID- 8491579 TI - Envenomation by Echis coloratus (Mid-East saw-scaled viper): a review of the literature and indications for treatment. AB - Envenomation by the snake Echis coloratus causes a local swelling and hemostatic failure. Most cases recover uneventfully, however about one-third of the victims bleed or develop anemia, and one known death due to renal failure has been reported. Uncontrolled observations suggest that treatment by a specific antivenom reduces the duration of the hemostatic failure. Still the management of victims of E coloratus remains uncertain. Some authors advocate antivenom treatment for all patients, while others recommend its use only in the event of complications. We review reported data on the effect of the venom in vitro, in laboratory animals and in humans, and reexamine alternative treatment strategies by applying a revised version of a published decision model. The probability of bleeding and the efficacy of antivenom treatment were the main determinants in the choice between antivenom treatment and expectant management of victims of E. coloratus. Assuming a therapeutic efficacy of 32%, the decision model favored antivenom treatment when the risk of bleeding exceeded 7.5%. The estimated risk of bleeding exceeds this threshold in patients who present with either proteinuria, a blood urea of > 7 mmol/l, a platelet count of < 100,000/microliters, or a hemoglobin level of < 13 g/dl. In patients who had been exposed to antiserum in the past, or in whom the annual probability of future envenomation exceeds 0.9%, antivenom treatment was preferred only when bleeding was certain. Errors in our estimates of the efficacy of antivenom treatment, of the mortality after a bleeding event and of the risk of anaphylaxis after a repeated exposure to antiserum may have affected our conclusions. Nonetheless, they are consistent with presently available information and, pending more reliable estimates, may be considered as guidelines for treatment. PMID- 8491580 TI - Ludwik Eleazar Zamenhof--the father of Esperanto. PMID- 8491581 TI - Primary and salvage surgery for cancer of the tonsillar region: a retrospective study of 120 patients. AB - The present series compares results in our head and neck department from primary and salvage surgery for tumors of the tonsillar region from 1978 to 1985. Of 120 consecutively admitted patients, 70 underwent primary surgery followed by irradiation, and 50 underwent salvage surgery after the failure of primary radiotherapy. Follow-up has been continued for the past 6 years. Musculocutaneous flaps were employed in all patients requiring them after the introduction of this reconstructive technique in 1981. The actuarial survival rate after primary surgery was 58% at 3 years and 46% at 5 years. For salvage surgery the figures were 38% and 24%, respectively. This disappointing survival rate in salvage surgery resulted from a higher postoperative mortality (8% versus 1.4% in primary surgery) and from a higher local failure rate (36% versus 14%). The outcome was invariably unfavorable when tonsillar tumors extended into the base of the tongue. PMID- 8491582 TI - Olfactory neuroblastoma: the results of modern treatment approaches at the University of Michigan. AB - A retrospective study was undertaken to review patterns of treatment and survival for patients with olfactory neuroblastomas at the University of Michigan since the introduction of craniofacial resection in the late 1970s. Recent results were compared to previous reports. Disease-free and overall survival for patients with Kadish stage B tumors were unchanged from prior years. Improvement in both disease-free intervals and overall survival was evident for patients with stage C tumors. Interestingly, in two patients with "unresectable" local disease, complete responses to induction chemotherapy followed by radiotherapy were noted. PMID- 8491584 TI - Intravenous fluid administration and urine output during radical neck surgery. AB - This study examines perioperative urine output (UO) and hemodynamics in 24 patients who underwent radical head and neck surgery. The hypothesis tested was that "UO was not important in patients with normal renal function as long as hemodynamics were maintained." Intraoperatively, a "wet" group (13 patients) had generous amounts of intravenous (IV) fluid administered during surgery receiving 1,018 +/- 58 mL.h-1. The other "dry" group (11 patients) had fluids restricted to 426 +/- 23 mL.h-1. The intraoperative UOs for the wet and dry groups were 1.33 +/ 0.27 and 0.39 +/- 0.10 mL.kg-1 x h-1, respectively (p < 0.05). Postoperatively, the UOs for the wet and dry groups were 1.9 +/- 0.3 and 1.1 +/- 0.1 mL.kg-1 x h 1, respectively (p < 0.05). Perioperatively, there were no statistically significant differences between groups in systemic or pulmonary hemodynamics. Postoperatively, ordinary indices of renal function remained normal in both groups. We conclude that intraoperative oliguria due to moderate fluid restriction is not detrimental to renal outcome as long as systemic hemodynamics are maintained. Furthermore, not only does this relatively "dry" status not compromise hemodynamics, it affords the patient other benefits. PMID- 8491583 TI - Cancer of the larynx in Mexico: review of 357 cases. AB - Descriptions of the patient population suffering from carcinoma of the larynx are not common in Mexico. This article deals with the clinical features, treatment, and results of 357 cases of cancer of the larynx treated at the Hospital de Oncologia, Centro Medico Nacional, IMSS, during a 10-year period. In this series, 68% of the patients were in advanced stage (T3-T4) at the time of diagnosis; nevertheless, a combination of surgery and radiotherapy achieved an actuarial 5 year survival for the entire group of 77.5%. Metastatic cervical nodes and tracheotomy previous to the treatment were factors that influenced a poor prognosis (p = 0.01). The survival of cases in the early stages (T1-T2) of 95.2% is comparable to that reported by most authors. In 87.5% of the cases that develop recurrence, it appears during the first 24 months of control. PMID- 8491585 TI - Innervation of the trapezius muscle by the intra-operative measurement of motor action potentials. AB - Although the surgical anatomy of the spinal accessory nerve and the cervical plexus has been extensively described, the exact motor innervation of the trapezius has been controversial. Attempts to resolve this question have involved anatomic or electrophysiologic studies in human embryos and animals. Extrapolation of the results to adult humans may not be correct. Accurate identification of muscle innervation is obtainable by intra-operative measurement of motor action potentials produced by direct stimulation of the accessory nerve and the cervical plexus. The study involved 14 patients undergoing supraomohyoid or modified neck dissections. Under direct vision, stimulating electrodes were placed on the identified nerves and motor action potentials, and latencies were recorded by surface electrodes placed over the three portions of the trapezius. In 13 patients, when the accessory nerve was stimulated, motor action potentials were obtained in 13 of 13 in the first portion, 11 of 13 in the second portion, and 10 of 13 in the third portion of the trapezius. In the last patient, the accessory nerve ended in the sternocleidomastoid muscle, and innervation of the trapezius was via C3 as demonstrated by motor action potentials. Responses when the roots of the cervical plexus were stimulated varied. Three patterns were seen: In the first group (seven patients), motor action potentials were distinct from those recorded when the accessory nerve was stimulated. Additionally, latencies were different from those of the accessory nerve. The second group (four patients) had motor action potentials that were similar to those obtained from stimulation of the accessory nerve, although their corresponding latencies were different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491586 TI - Correlation between nodal density in contrasted scans and response to cisplatin based chemotherapy in head and neck squamous cell cancer: a prospective validation. AB - This prospective study was done to validate an earlier retrospective study demonstrating a relationship between complete response to chemotherapy and nodal density as estimated in contrasted computed tomography (CT scans) in head and neck squamous cell carcinoma (HNSCC). CT scans of 36 patients were evaluated by two radiologists blinded to therapeutic outcome. The density of the largest node (> 2 cm) was compared to that of nuchal muscles. A node was classified as hypodense if more than 33% of the nodal surface area consisted of hypodense zones. Density and nodal staging were related: 67% (10 of 15) of patients with N3 disease but only 29% (six of 21) with N1-N2 exhibited isodensity, p < 0.05. Complete response to chemotherapy was noted in 63% (10 of 16) of the isodense group but only in 15% (three of 20) of the hypodense group, p < 0.01. We believe that nodal density can be used for therapeutic decision-making in high nodal volume HNSCC. PMID- 8491587 TI - Hyperbaric oxygen therapy and squamous cell carcinoma cell line growth. AB - Hyperbaric oxygen (HBO) promotes tissue healing by increasing oxygenation. Therefore, HBO therapy is clinically useful for some patients who have undergone major cancer resection and/or radiotherapy to the head and neck. For individual patients, however, there might be undetected viable tumor present at the time of therapy. This study was performed to determine if increased tissue oxygen had a measurable effect on the growth of squamous carcinoma xenotransplants which had been derived from head and neck cancers. After the successful growth of two well established human squamous cell carcinoma cell lines (183 and 1483), each tumor was transplanted into 20 mice. Every mouse received four transplants of 10(6) cells. Ten mice with 40 xenotransplants in each group were treated with HBO daily for 90 minutes at a pressure of 2 atm, whereas the other 10 formed the control group. The mice transplanted with cell line 1483 were treated for 21 days; mice transplanted with cell line 183 were treated for 28 days. The tumor weight, volume, and histology were evaluated. No significant difference was found between experimental groups. This study suggests that increased tissue oxygen neither significantly increases nor decreases the growth of squamous cell carcinoma. PMID- 8491588 TI - Neoplastic seeding of squamous cell carcinoma of the oropharynx. AB - Neoplastic seeding is a concept of mechanical disruption and spread of tumor into normal tissues. It is well-documented and accepted as an explanation for unusual patterns of tumor recurrence at multiple sites in the body. Neoplastic seeding is often invoked as an explanation for stromal recurrences following treatment of laryngeal carcinoma. However, it is impossible to discern whether these recurrences represent peritracheal lymph nodes, persistent or recurrent local disease, or neoplastic seeding of tumor. The purpose of this article is to report two cases of tracheostomy site recurrences after treatment of oropharyngeal squamous carcinoma, in which neoplastic seeding is the most plausible explanation of recurrence. The rarity of this phenomenon appears strikingly small despite significant experimental evidence supporting the possibility of its occurrence. Although specific recommendations for prevention cannot be made, it appears prudent to avoid re-use of instruments that come into direct contact with squamous cell carcinoma tumor surface. PMID- 8491589 TI - Radiotherapy for basaloid squamous cell carcinoma of the head and neck. AB - Basaloid squamous cell carcinoma (BSCC) of the head and neck is a recently described high-grade variant of squamous cell carcinoma. It is a biologically virulent neoplasm with a propensity for nodal, as well as systemic, metastases. Because of the limited number of published reports, we reviewed data from patients of the University of Virginia Health Sciences Center and identified 16 cases of BSCC. The intent of this study was to determine the role of radiotherapy in the treatment of BSCC and better define the clinical features of this entity. Radiotherapy alone, or in combination with surgery, resulted in excellent local control rates. Distant metastases, chiefly pulmonary, occurred in more than half of the patients. PMID- 8491590 TI - Inversion of Zenker's diverticulum: the preferred option. AB - A review of patients who had surgery for Zenker's diverticulum in our institution in recent years was conducted. A comparison of inversion versus excision of the sac shows that inversion carries lower morbidity and more rapid rehabilitation of swallowing than does excision. Inversion (plus cricopharyngeal myotomy) is to be preferred for diverticula that are neither too large to invert nor too longstanding to risk leaving subclinical carcinoma behind in the wall of the diverticulum. PMID- 8491591 TI - Manifestations of metastatic breast carcinoma to the head and neck. AB - Although metastatic neoplasms in the head and neck are rare compared to primary head and neck neoplasms, metastatic breast carcinoma has been described at numerous sites in the head and neck region. Two cases of breast carcinoma metastatic to sites in the head and neck are reported. In one case a laryngeal metastasis represented the first manifestation of recurrent breast cancer. The second case, a nasal metastasis, was unsuspected and was treated as cellulitis. The presentation of metastatic breast carcinoma to the head and neck may in fact be atypical, posing a diagnostic dilemma. These cases illustrate the importance of past medical history and the high index of suspicion in patients with a history of prior malignancy. PMID- 8491592 TI - Treatment of a nonfunctioning parathyroid cyst with tetracycline injection. AB - Parathyroid cysts are uncommon: about 200 cases have been reported. They can be functional (i.e., accompanied by signs of primary hyperparathyroidism), or nonfunctional. Preoperative diagnosis is difficult, although it has become increasingly frequent with the use of ultrasound and fine-needle aspiration biopsy. Fluid of parathyroid cysts is almost invariably watery, colorless, and crystal clear, which should cause clinical suspicion. However, definitive diagnosis relies on the demonstration of high parathyroid hormone (PTH) levels in the fluid. Puncture may cure nonfunctioning cysts, but surgery is indicated when the lesion recurs after several fine-needle aspirations. We report a case of a nonfunctioning parathyroid cyst in a 17-year-old boy, which reappeared after two punctures made 6 months apart. On the third occasion, 1 mL of a sterile tetracycline solution injected into the cyst cured the lesion. Tetracycline and other sclerosants have been recommended as a treatment of recurring thyroid cysts. We suggest that injection of a sclerosant should be considered as an alternative to surgery in recurring, nonfunctional cysts of the parathyroid glands. PMID- 8491593 TI - Immunomodulation therapy for squamous cell carcinoma of the head and neck. AB - The role of the immune system in the pathogenesis and treatment of cancer is currently a popular area of research. An underlying fundamental concept of cancer immunology is the supposition that tumor cells express antigens differently than normal cells, both qualitatively and quantitatively. Understanding tumor-host interactions may suggest opportunities to modify these relationships to obtain antitumor effects. There is growing evidence that the immune system plays an important role in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). Based on this evidence, trials studying the therapeutic efficacy of biologic response modifiers (BRMs) have been undertaken. These trials have had variable success, but continued efforts incorporating newer cytokines are underway. PMID- 8491594 TI - Harmonization of radon jargon and units. PMID- 8491595 TI - Determining person-years of life lost using the BEIR V method. AB - A method is given that permits the calculation of the estimated person-years of life lost when groups of males or females are exposed to low linear energy transfer (LET) ionizing radiation. It is felt that this determination is informative in rating risks to populations from radiation exposures. For example, when 1,000,000 females have received an acute 10 mSv, the total number of radiation-induced fatal cancers is 835. The total number of person-years of life lost is 1.4 x 10(4) or an average of about 5 d. However, the 22 who die of leukemia suffer an average of about 34 y. Those who die of other forms of cancer lose an average of 16 y. Some examples have been reported by the U.S. National Academy of Sciences (1990) report. In those cases where the Committee presented results, the method given here is in good agreement. PMID- 8491596 TI - A-bomb survivors: further evidence of late effects of early deaths. AB - Reanalysis of A-bomb survivor data has shown the following: a) in the high-dose (> 1 Gy) subgroups of the life span study cohort of 5-y survivors, there is a significant deficit of individuals who were < 10 y or > 50 y at the time of the bomb; and b) in the cohort on in utero children, there is a significant deficit of individuals who were < 8 wk of fetal age when exposed. This paper discusses how this selection bias has affected the perception of three effects of A-bomb radiation: marrow damage, carcinogenesis, and second-generation effects. PMID- 8491597 TI - Dose assessment for recent inhabitants living adjacent to zones heavily contaminated from the Chernobyl fallout. AB - Within the framework of the "International Chernobyl Project," selected areas in the Republics of Ukraine, Belarus, and Russia of the former USSR, contaminated by radioactive fallout from the Chernobyl accident in 1986, were investigated by international teams. In addition, environmental studies were carried out in areas officially declared as "uncontaminated regions" in order to corroborate this classification and to provide reference baseline data for the simultaneously performed medical investigations on health effects in the contaminated areas. Altogether, 141 measurements of the gamma dose rate, both outdoors and indoors, were carried out. Also, the radionuclide concentration in 58 soil and food sample was determined. In addition, results from 1,620 individual film dosimeter readings were analyzed. The results show that, in areas adjacent to those officially designated as contaminated regions (137Cs surface ground contamination > or = 37 kBq m-2), levels of environmental fallout contamination are insignificant. The additional resulting committed effective dose over the next 70 years due to the fallout is only a fraction of the corresponding value from the natural radiation environment. PMID- 8491598 TI - Profiles and downward migration of 134Cs and 106Ru deposited on Italian soils after the Chernobyl accident. AB - After the Chernobyl accident, several radionuclides were deposited on the soil of the Piemonte Region in Italy. Contamination values were monitored and the initial vertical soil profiles of 134Cs and 106Ru were determined. For both radionuclides, more than 60% of the total activity remained in the upper 1-cm layer of soil during the first 7 mo after the accident. The time history of the soil profiles was studied over a period of 3 y in two Piedmontese localities. A compartmental model was also developed to describe downward migration of 134Cs and 106Ru. The results indicated a low mobility for both radionuclides. The change in their vertical profiles may be described using a box model with a transfer constant of 0.2 y-1 for 134Cs and 0.3 y-1 for 106Ru between 1-cm-thick layers. A strong association between the soil fine fraction and the mobility of both radionuclides was also found. PMID- 8491599 TI - Long-term radon concentrations estimated from 210Po embedded in glass. AB - Measured surface-alpha activity on glass exposed in radon chambers and houses has a linear correlation to the integrated radon exposure. Experimental results in chambers and houses have been obtained on glass exposed to radon concentrations between 100 Bq m-3 and 9 MBq m-3 for periods of a few days to several years. Theoretical calculations support the experimental results through a model that predicts the fractions of airborne activity that deposit and become embedded or adsorbed. The combination of measured activity and calculated embedded fraction for a given deposition environment can be applied to most indoor areas and produces a better estimate for lifetime radon exposure than estimates based on short-term indoor radon measurements. PMID- 8491600 TI - Dose quantities and instrumentation for measuring environmental gamma radiation during emergencies. AB - The dosimetry for exposure to gamma radiation in the environment is reviewed, including the factors used to convert measurements of traceable quantities to effective dose equivalent. A value of 0.70 Sv Gy-1 is widely used to convert air kerma or absorbed dose-to-air to effective dose equivalent, but recent work shows that a value of 0.86 Sv Gy-1 is more appropriate for deposited radionuclides. The arguments are reviewed and the implications of using operational dose equivalent quantities defined by the International Commission on Radiation Units and Measurements are considered. For planar deposited sources in the environment, it is shown that the use of ambient dose equivalent quantities without applying conversion factors, could significantly overestimate effective dose equivalent. In contrast, the adoption of the new effective dose quantity defined by the International Commission on Radiological Protection in Publication 60 will have a small impact on conversion factors for gamma radiation in the environment. Practical aspects of measurement are also considered, and five instruments suitable for measuring environmental gamma radiation have been evaluated in the laboratory and in field tests. The instruments include models with scintillation detectors, a Geiger-Muller detector, and a high-pressure ionization chamber, the choice being influenced by those commonly used in European Community countries for routine and emergency monitoring. The main disadvantage of all the instruments is the lack of spectral information, so a straightforward emergency instrument capable of discriminating between natural and artificial radionuclides has also been evaluated. PMID- 8491601 TI - The relationship of effective dose to personnel and monitor reading for simulated fluoroscopic irradiation conditions. AB - The exposure of staff during fluoroscopic procedures was simulated for overcouch x-ray tube/undercouch image intensifier and undercouch x-ray tube/overcouch image intensifier geometries. A Rando phantom with film badge dosimeters attached to the skin surface at seven commonly used monitoring sites and loaded with lithium fluoride thermoluminescent dosimeters was irradiated for an extended period in the vicinity of a patient couch. Scattered radiation generated from the irradiation of an anthropomorphic phantom using primary radiation in the range of 70 kVp-110 kVp was used. The radiation dose to organs which were shielded by a lead apron was estimated from the unattenuated organ dose readings by applying an experimentally determined scattered radiation transmission factor. The ratio of effective dose to film badge reading was obtained for a range of irradiation conditions and lead apron thicknesses. For most irradiation conditions studied, a dosimeter worn above the lead apron will significantly overestimate effective dose by a factor of between 2 and 60, depending on the irradiation conditions. A dosimeter worn under the apron at either waist or chest level, will generally yield a closer (although usually an underestimate of) effective dose, typically within a factor of 7 for the most common lead apron thicknesses and irradiation conditions. No single dosimeter can accurately monitor effective dose for all irradiation conditions in fluoroscopy. PMID- 8491602 TI - Lifespan studies in rats exposed to 239PuO2 aerosol. AB - Spatial-temporal dose-distribution patterns in the lung continually change following inhalation of radionuclides. Lung clearance, microdosimetry, and radiation dose were examined in female Wistar rats exposed to high-fired 169Yb2O3 239PuO2 aerosols. Whole-body counting for 169Yb at 14 d postexposure provided an accurate (r = 0.99) estimate of 239Pu lung content. Alpha irradiation of tracheal epithelium was at least 50 times less than for bronchiolar epithelium due principally to preferential retention of 239PuO2 in peribronchiolar alveoli as compared to other alveolar regions. The formation of large aggregates (> 25 particles) increased linearly with initial lung burden starting at 0.4 kBq; mean dose rate to these focal alveolar regions was 120 Gy d-1. Concentration of 239PuO2 in pulmonary macrophages and in aggregates, along with the limited penetration of alpha particles in tissue, resulted in a highly nonhomogeneous dose distribution pattern. Alveolar clearance was best represented by a biphasic clearance curve comprised of a rapid early phase (80% initial lung burden) and a slow late phase (20% initial lung burden). Studies with intratracheally instilled 237PuO2-239PuO2 and with inhaled 239PuO2 showed that alveolar clearance was inversely proportional to initial lung burden. A single clearance function was derived from experimentally determined clearance curves for inhaled 239PuO2 that was used to accurately estimate lung dose at all initial lung burden levels. Lung doses were calculated for 2,105 exposed lifespan rats based on individually determined initial lung burden, survival time, and individually computed clearance function. PMID- 8491603 TI - On communication and comparison of radiation risks. AB - Comparison with other risks helps to put a radiation risk into perspective and facilitates communication of radiation risk to the public. Twelve recommendations for risk comparisons are given, and some guidelines for risk communication are discussed. PMID- 8491604 TI - Chromosome aberrations in human lymphocytes apparently induced by Chernobyl fallout. AB - Sixteen people (15 from Byelorussia, one from Kiev) possibly exposed to radioactivity released by the Chernobyl accident were investigated for chromosome aberrations induced in lymphocytes. Statistically significant increases of the yield of dicentric chromosomes were observed in five people. PMID- 8491605 TI - Differences in the sensitivity of barley varieties to direct cesium contamination from the Chernobyl accident. AB - A number of winter and spring barley (Hordeum vulgare L) varieties were tested for sensitivity to direct cesium contamination in Denmark arising from the Chernobyl accident. Significant differences among varieties were revealed which were independent of crop growing conditions. Results indicate that different sensitivities among varieties result from genetic or morphological differences. PMID- 8491606 TI - An assessment of overbadging at a large clinic. AB - We have analyzed the need to have personnel monitors worn by over 400 individuals in our clinic. We grouped individual's personnel monitoring results according to job classification and averaged each classification's readings for 18 mo. From these averages, we were able to clearly define an "essential to monitor" group and a "not essential to monitor" group (83 muSv per monitor per mo vs. 7 muSv per monitor per mo). We then performed a cost-benefit analysis on the results and compared the cost per sievert detected with the cost per theoretical cancer induced. The result was compared with the monetary value assigned per unit collective dose used in NCRP Report No. 107. PMID- 8491607 TI - Wipe testing for surface contamination by tritiated compounds. AB - This study investigated the performance of the wipe test in determining contamination from tritiated triolein or thymidine on various surfaces. Filter papers were saturated with water, methanol, petroleum ether, ethyl acetate or maintained dry, and wipes were taken from lead, stainless steel, polyurethane, wood, painted lead, treated floor tile, Formica, or bench paper that were spotted with either 3H-thymidine or 3H-triolein. The recovery of contamination using the dry wipe test averaged 3% for all surfaces. Recoveries using wet wipes were directly related to the solubility of the tritiated compounds in the wipe solution and the physical nature of the wipe surface. PMID- 8491608 TI - Reflections on NCRP Statement No. 7. PMID- 8491609 TI - Re: Probability of causation. PMID- 8491610 TI - Clinical viewpoint on NCRP probability of causation statement. PMID- 8491611 TI - Quality of radon measurements. PMID- 8491612 TI - Mortality of workers at the Hanford site: 1945-1986. AB - Updated analyses of mortality of workers at the Hanford site provide little evidence of a positive correlation of cumulative occupational radiation dose and mortality from leukemia and from all cancer except leukemia. Estimates of the excess relative risk per 10 mSv were negative for both disease categories, but these estimates are consistent both with no risk and with estimates obtained through extrapolation from high-dose data. For all cancer except leukemia, the upper limit for a two-sided 90% confidence interval was about 1.5 times the prediction of the BEIR V model, but several times the estimate recommended by the ICRP 60 committee. For leukemia, the comparable upper limit was very close to that predicted by either BEIR V or ICRP 60. The all-cancer risk estimate, from a recent report on updated analyses of data for Oak Ridge National Laboratory workers, was strongly rejected based on the Hanford data. Of 24 specific cancer categories evaluated, only cancer of the pancreas and Hodgkin's disease showed positive correlations with radiation dose that approached statistical significance with one-tailed p values of 0.07 and 0.04, respectively; these correlations are interpreted as probably spurious. For multiple myeloma, for which a correlation was reported previously, the p value was 0.10. However, a significant correlation (p < .05) was obtained when analyses were expanded to include deaths with multiple myeloma listed on the death certificate but not considered to be the underlying cause, when analyses were expanded to include deaths occurring in Washington State during the time period 1987-1989, or when a 2-y latency period (instead of 10-y) was assumed. PMID- 8491613 TI - Diagnostic x-ray examinations in Poland in 1986--frequency and type. AB - This paper presents the results of a survey concerning x-ray diagnostic examinations in Poland as the main source of radiation risk to the general population. The methods of data acquisition and processing are described. In Poland, 21,400,000 patients (572 examinations per 1,000 inhabitants) are annually subjected to diagnostic x-ray examinations. The age and gender structure of examined patients is discussed extensively. Special attention is paid to the share of children and youth in the total number of examined patients. The obtained results are compared with the numerical data for other European countries. PMID- 8491614 TI - Ukrainian thyroid doses after the Chernobyl accident. AB - To estimate thyroid radioactivity in the Ukrainian population from May-June 1986, more than 150,000 individual examinations were carried out by special dosimetric teams. The results of these total measurements were approved to be a basis for assessing individual absorbed doses of infant and adult thyroid irradiation associated with the 131I exposure. The dosimetric radioiodine data bank of thyroid irradiation of the Ukrainian population was created to analyze these measurements. The analysis was performed using the data for eight Ukrainian districts and the town of Pripjat, which were all heavily contaminated due to radioiodine exposure. Results of the dose assessments are given using two models: the more conservative model of "single radioiodine intake" and a more realistic model that considers the individual duration of radioiodine intake. In accordance with the more realistic model, the predictions of late effects have shown that a collective thyro-oncogenic dose is equal to 64,000 person-Gy, stimulating the possibility of the emergence of 300 cases (30 incurable) of thyrocancers. Considering this information for the next 35 y (1991-2026), it is possible to predict a 1.4-fold increase over spontaneous thyroid cancer morbidity for children who lived in the heavily contaminated regions of the Ukraine in 1986 (spontaneous and radiogenic to spontaneous). PMID- 8491615 TI - Human uptake of 137Cs in mutton. AB - The uptake of radiocesium from mutton contaminated by fallout from the Chernobyl reactor accident has been studied in eight healthy male volunteers. Each subject consumed, on adjacent days, two meals prepared from the mutton containing a total of 0.8 kBq 137Cs. The elevation and subsequent decline in whole-body content were determined from body radioactivity measurements prior to the meals and at intervals up to 15 wk afterwards. Clearance of 137Cs between 1 and 15 wk showed a biological half-time of 102 +/- 24 (SD) d, (range 84-154 d). The fraction cleared with this half-time was 80 +/- 4% (range 72-85%). No attempt was made to determine the early retention and excretion but, if the ICRP's assumption of 10% clearance with a 2-d half-life were valid, the data would indicate an average uptake (f1) of 89%, i.e., marginally lower than the value of 100% assumed in setting limits on intake. PMID- 8491616 TI - 222Rn in Greek spa waters: correlation with rainfall and seismic activities. AB - In our previous research, the natural radioisotopes (including 222Rn) present in the waters of the Greek spas Ikaria, Kamena Vourla, and Loutraki, were determined by gamma-spectroscopy, laboratory method. Large variations of 222Rn were found in different samples from the same spa. In order to explain these variations, the effect of rainfall before the sampling date was examined. It was concluded that rainfall decreased (or drought increased) the 222Rn concentrations in most cases. The explanation for the exceptions may be the effect of earthquakes. Characteristics considered include time, depth, magnitude, and distance of the epicenters from the spa. From the results, it can be concluded that the earthquakes increased 222Rn concentrations. PMID- 8491617 TI - Radon exhalation rate from various building materials. AB - Solid-state alpha-track detectors using cellulose nitrate films were used to measure the radon exhalation rates from building materials. The radon flux emitted from the surface of the building material was measured by placing an inverted cup on the top of the building material. Cellulose nitrate film was placed within the cup. Tracks due to alpha particles from radon that migrate from the building material into the air space in the cup were registered on the cellulose nitrate film. The films were etched in a solution consisting of 10(-3) m3 2.5 N NaOH solution. A spark counter or microscope was used to record the tracks appearing on the cellulose nitrate film. The average exhalation rate of radon was obtained by means of a simple mathematical approach that can be used to estimate the maximum possible radon concentration in a closed room due to building materials alone. Infiltration and ventilation effects were excluded in this work. This new technique and simple approach can be used to establish the data base for average radon exhalation rates from all available building materials and walls or floors. The maximum indoor radon concentration can be estimated from the measured average radon exhalation rate by using this simplified model. PMID- 8491618 TI - Measurement of radioactivity levels in soil in the Nile Delta and middle Egypt. AB - Concentrations of radionuclides in surface soil across the Nile Delta, the north coast of Egypt, and Middle Egypt have been measured using a hyperpure germanium spectrometer. The concentrations obtained for 40K, the 232Th series, and the 226Ra series are expressed in Bq kg-1 of dry weight, and the exposure rates are expressed in nGy h-1 of wet weight. The activity concentrations of 137Cs in soil are expressed in Bq m-2. PMID- 8491619 TI - Specific absorption rate and radiofrequency current-to-ground in human models exposed to near-field irradiation. AB - To expand our knowledge of near-field radiofrequency energy absorption in occupationally exposed workers, we used coffin-sized calorimeters to measure specific absorption rate in full-size human models. The models were subjected to near-field irradiation at two frequencies at an outdoor groundplane facility. We also measured radiofrequency current-to-ground in the models to supplement a previous study at 29.9000 MHz. The results have enabled us to construct a frequency-independent mathematical relationship between specific absorption rate and radiofrequency current for the given exposure system. Moreover, the results show a favorable comparison to radiofrequency radiation dosimetry handbook predictions of average specific absorption rate when only the vertical electric field (E-field) component is used to normalize specific absorption rate. Once determined on a case-by-case basis, the use of specific absorption rate vs. radiofrequency current curves for any exposure system or condition could be a simple and quick method to determine onsite compliance with specific absorption rate-based exposure standards. PMID- 8491620 TI - A Monte Carlo approach to assessing 147Pm in the liver of the adult phantom. AB - A low-background phoswich detector is used to detect small amounts of 147Pm--a pure beta-emitting nuclide--present in the liver of an occupational worker. The assessment was based on the measurement of bremsstrahlung radiation produced by the beta particles in the tissue. Computer programs based on Monte Carlo techniques for photon transport have been developed to calculate the response of an external phoswich detector to 1) a 147Pm point source embedded in tissue equivalent slabs of various thicknesses; and 2) various source distributions of 147Pm in the liver of an adult phantom. The goal is to theoretically calibrate the phoswich detector for each source distribution and to study the variation of maxima of the spectra with the depth of the source in the adult phantom liver and tissue-equivalent slabs. The initial bremsstrahlung photon distribution of 147Pm in water has been computed using Wyard's and Pratt's methods. These calculations have been compared with experimental measurements using Perspex acrylic sheet slabs. Good agreements have been noted when the initial bremsstrahlung spectrum is obtained by using Wyard's method. These results find applications in monitoring the liver burdens in occupational workers handling 147Pm-based radioluminous paints. PMID- 8491621 TI - Evaluation of an alpha probe detector for in vitro cellular dosimetry. AB - This paper describes the design and testing of an alpha probe detector for the continuous measurement of the activity concentrations of alpha emitters in the culture media of in vitro cell suspension irradiation systems. The probe detector consists of a pen-size body housing a small silicon surface-barrier detector with a Mylar window. Theoretical calculations were performed to study the dependence of the alpha-energy spectrum on 1) the thickness of the Mylar barrier; 2) the Mylar-detector distance; and 3) the size of the detector window. These design parameters were selected by taking a compromise between the counting efficiency, the integrity of the detector, and its required range of application. The probe detector was tested using both chelated and unchelated 212Bi and 212Pb standard solutions; plate-out of these radionuclides on the Mylar barrier was observed for unchelated solutions. Alpha energy spectra were analyzed using a total integration technique. The measured activity concentrations and the calibrated values agree to within 4% for the chelated 212Bi and to within 6% for the unchelated 212Bi. The alpha probe detector can be used throughout an entire exposure time period to determine the total dose received by suspended cells, or at different time intervals to determine the dose rate in real time. PMID- 8491622 TI - 241Am-induced thyroid lesions in the beagle. AB - One of the features of 241Am metabolism in the beagle dog is a relatively high selective deposition in the thyroid glands, equal to approximately 0.06% of the injected dosage per gram. Retention is prolonged and principally in the interstitial connective tissue. The resulting average dose to the thyroid glands is about 1.42 and 0.76 times that delivered to the skeleton and the liver, respectively. This thyroid dose is much higher than has been reported in people. Although significant morphological changes and reductions in serum thyroxine occurred in this experiment, a significant increase in thyroid neoplasia was not observed. PMID- 8491623 TI - What is a reasonable cost for protection against radiation and other risks? AB - In Sweden, the National Audit Bureau is encouraging attempts at discussing the costs of protection. For many years, a government authority considering new regulations must provide the government with background material illustrating the costs, the expected benefits, and other aspects of the decision. Direct costs should be stated together with nonquantifiable factors indicated by a valuation of whether their consequences are positive or negative. Applied to radiation protection, this includes discussion of the resources worth spending in order to prevent a case of serious radiation injury. If the marginal cost for a protective measure is < 5 million Swedish crowns (5 MSEK: approximately 1 million U.S. dollars) per prevented case, the radiation protection authority considers the measure to be strongly justified. If the cost exceeds 25 MSEK per case, then very strong reasons are required for implementation of the measure. In the intermediate interval, measures are particularly justified if the marginal costs are in the lower end and the total societal cost of the protection is of little concern at the national economical level. The interval 5-25 MSEK per case corresponds to 0.4-2 MSEK person-sievert-1. Resource allocation for health protection in general, ethical aspects, and practical difficulties in assessing costs and risks are briefly discussed in the paper. Priorities in Swedish radiation protection are presented and a case study for the use of carbon fiber cassettes in x-ray diagnostics is given as an example. PMID- 8491624 TI - Class I and II HLA typing after a 10 Gy-4 hour therapeutic total body irradiation. AB - Class I and II HLA typing was investigated before and at various intervals after a 10 Gy total body irradiation delivered over 4 h, prior to allogeneic bone marrow graft for various hematological malignancies, in 14 patients. A reliable class I HLA typing appeared to be possible in almost all cases 6-8 hours after the start of irradiation but was only possible in 5 patients after 24 h. Preliminary results with class II antigens might suggest a more marked "fragility" of this antigen class after irradiation. These results encourage the drawing of blood samples for HLA grouping as soon as possible after accidental whole-body irradiation. PMID- 8491625 TI - 137Cs levels in deer following the Three Mile Island accident. AB - White-tailed deer (Odocoileus virgianus) tongues were assayed to assess whether or not significant widespread 137Cs contamination occurred in the vicinity of Three Mile Island Nuclear Station as a result of the 1979 accident. White-tailed deer tongues harvested from 10 Pennsylvania counties more than 88 km away from Three Mile Island had significantly higher 137Cs levels than deer tongues harvested from counties surrounding the nuclear plant. The mean deer tongue 137Cs levels found in Pennsylvania white-tailed deer were lower than 137Cs levels found in deer from other parts of the U.S. sampled shortly after culmination of major atmospheric nuclear testing. These findings support the conclusions of previous studies suggesting that only minimal quantities of 137Cs escaped from the damaged Three Mile Island plant after the accident. PMID- 8491626 TI - Shielding for beta-gamma radiation. AB - The build-up factor, B, for lead was expressed as a polynominal cubic function of the relaxation length, mu x, and incorporated in a "general beta-gamma shielding equation." A computer program was written to determine shielding thickness for polyenergetic beta-gamma sources without resorting to the conventional "add-one HVL" method. PMID- 8491627 TI - Beta zoomies. PMID- 8491628 TI - Leukemia risk from diagnostic X-ray examinations--a clinical perspective. PMID- 8491629 TI - Designated driver campaign. PMID- 8491630 TI - Development of level of institutionalization scales for health promotion programs. AB - This study was conducted to test an instrument for measuring the level of institutionalization (LoIn) of health promotion programs. Institutionalization occurs when a program becomes an integral part of an organization, and the LoIn instrument is a beginning effort to measure the extent of program integration into organizations. The instrument is based on theory that holds that organizations are composed of production, maintenance, supportive, and managerial subsystems. Institutionalization occurs when a program becomes imbedded into these subsystems. A questionnaire designed to test this construct was mailed to 453 administrators in 141 organizations that operate health promotion programs. Based on 322 usable responses (71%), a confirmatory factor analysis was conducted. The results support the hypothesis of an eight-factor model: four factors concern how routinized the program was in each subsystem and four factors concern the degree of program saturation within each subsystem. Correlations of the eight factors with the number of years the programs had been in operation, and managers' perceptions of program permanency, indicated that the four routinization factors were more highly correlated with program longevity than the four niche saturation factors, and the niche saturation factors were more highly correlated with managers' perceptions of program permanence than the routinization factors. The instrument, which is available from the authors, may be used as both a research instrument and a diagnostic tool in assessing the institutionalization of health promotion programs. PMID- 8491631 TI - Are the level of institutionalization scales ready for "prime time"? A commentary on "Development of level of institutionalization (LoIn) scales for health promotion programs". PMID- 8491632 TI - Health insurance coverage for smoking cessation services. AB - The health benefits from quitting smoking have been well documented; however, most health insurance plans in the United States, both public and private, have excluded coverage of smoking cessation services. Since 1988, numerous public health policy documents have called for health insurance coverage of smoking cessation services, although there is little agreement over what kinds of services or interventions are most appropriate for health insurance coverage. The purposes of this paper are to (1) describe current public policy for health insurance coverage of smoking cessation services; (2) review the current status of policy adoption by private health insurance carriers, health maintenance organizations, self-funded employers, as well as public insurance programs including Medicare and Medicaid; (3) analyze the major barriers faced by health insurers, health care providers and policy makers in offering coverage for smoking cessation services; and (4) outline the specific policy options that the federal government, state governments, employers and anti-smoking coalitions can take to increase insurance coverage for smoking cessation services. The paper concludes with recommendations for practitioners, researchers and policy makers. PMID- 8491633 TI - Commentary: Financing and reimbursement for health promotion and education- innovative strategies for implementation and dissemination are needed. PMID- 8491634 TI - Development and validation of the Parent Health Locus of Control scales. AB - We describe the development and validation of the Parent Health Locus of Control (PHLOC) scales. Using factor analytic and item analytic methods, 30 items comprising six scales were extracted from a pool of 84 items. The individual scales correspond to beliefs in Child, Divine, Fate, Media, Parental, and Professional Influence over child health. Results were compared for six samples totalling 822 parents. Internal consistency reliabilities were above .70 for all scales with all samples. Test-retest correlations based on a separate sample were all above .60. Validity was assessed by means of a known groups strategy that made use of presumed differences among the six samples studied. The results generally agreed with predicted differences, offering good initial evidence of the validity for the PHLOC scales. PMID- 8491635 TI - Changing adolescent propensities to use drugs: results from Project ALERT. AB - Do successful drug prevention programs suppress the risk factors they were intended to modify? This paper addresses that issue for Project ALERT, a school based program for seventh and eighth graders that has been shown to curb both cigarette and marijuana use. Evaluated with over 4,000 students in an experimental test that included 30 diverse California and Oregon schools, the curriculum seeks to help young people develop both the motivation to avoid drugs and the skills they need to resist pro-drug pressures. Using regression analyses, we examine the program's impact on the intervening (cognitive) variables hypothesized to affect actual use: adolescent beliefs in their ability to resist, perceived consequences of use, normative perceptions about peer use and tolerance of drugs, and expectations of future use. The analysis depicts program effects for perceptions linked to each target substance (alcohol, cigarettes, and marijuana), across all students and for those at different levels of risk for future use. Results show that the curriculum successfully dampened cognitive risk factors from each of the above categories for both cigarettes and marijuana, indicating that social influence programs can mitigate a broad range of beliefs associated with the propensity to use drugs. However, it had a limited impact on beliefs about alcohol, the most widely used and socially accepted of the three drugs. Implications for drug prevention programs and practitioners are discussed. PMID- 8491636 TI - Relationship of mothers' food choice criteria to food intake of preschool children: identification of family subgroups. AB - This study investigated the relationship between potential criteria mothers use to select foods for their children, their food knowledge, and food consumption of their children. Participants were 218 predominantly Latino mothers and their 4 to 5-year-old children. Mothers rated 17 foods in terms of 10 food attributes (how tasty specific foods were to their child, whether they were convenient to prepare, etc.). Within-person correlation coefficients were then calculated between these ratings and reported frequency of consumption of these same 17 foods. These correlations were then used in a k-means cluster analysis to identify six distinct subgroups of families, who had different orientations ranging from "high health" to "high taste." Children in the "high health" groups had diets significantly lower in calories, fat, saturated fat, and sucrose and higher in fiber and vitamin A from 24-hour dietary recalls reported by mothers. Mothers' health knowledge was also correlated with nutrient takes of children. These data indicate that families can be segmented according to the importance of beliefs about healthfulness of foods and that this segmentation predicts quality of diet of children. This study suggests that interventions should be designed to increase mothers beliefs in the importance of health in choosing foods. For those mothers whose food choices are dominated by children's tastes, interventions should be directed at how to prepare healthful foods to taste good to children. PMID- 8491637 TI - Barriers to human immunodeficiency virus related risk reduction among male street prostitutes. AB - Two hundred eleven male street prostitutes between the ages of 18 and 51 years were interviewed and tested for antibodies to the human immunodeficiency virus (HIV). Economic, social, and emotional barriers to the reduction of HIV-related risk behavior were examined within the context of several concepts present in the Health Belief Model (HBM). Three lifestyle factors were found to function as barriers to engaging in risk reduction behavior. Subjects who were more economically dependent on prostitution, perceived less control over the hustling encounter, and reported increased pleasure from sexual activity with their customers were more likely to engage in risk-taking behavior. Prostitutes' perception of the severity of HIV infection was not significantly associated with their risk behavior. Unexpected findings indicated that increases in perceived susceptibility to HIV and perceived benefit of condom use for HIV prevention were significantly related to increased risk-taking behavior. Practical applications of findings in the design and implementation of future HIV-related preventive health education programs are discussed. PMID- 8491639 TI - Making connections. PMID- 8491638 TI - Evaluation of interventions to improve solar protection in primary schools. AB - Childhood and adolescence are critical periods in the etiology of subsequent melanoma and nonmelanocytic skin cancers. The aims of the study were (a) to develop a valid measure of solar protection in 9 to 11-year-old school students, (b) to evaluate the differential effectiveness of two interventions aimed at changing solar protection in this age group, and (c) to identify the predictors of use of a high level of solar protection. A Solar Protection Behavior Diary was developed and validated during a pilot, after which 11 schools were randomly allocated to one of three groups: intensive intervention (247 students), standard intervention (180 students), or control (185 students), with students in years 5 and 6 participating in the study. Students completed the validated diary (for 5 days) and a knowledge and attitudes questionnaire at pretest and at two posttest periods (4 weeks and 8 months after pretest). Results indicated that students in the intensive intervention group were significantly more likely to have used a high level of protection at both posttest periods compared to the control and standard intervention groups. There was no difference in the protection level of the control and standard intervention groups at either posttest, indicating that this minimal intervention was not effective in changing the solar protection behavior of the students. Students with a high level of solar protection at pretest were also significantly more likely to have a high level of protection at both posttest periods, and those with a greater number of opportunities to protect were less likely to protect at the second posttest. PMID- 8491640 TI - No right to silence. AB - Enforcement of maintenance payments by absent parents will not necessarily mean the child is better off. Women who refuse to disclose the identity of the absent parent may face deductions from their state benefits. In the first of two articles Beth Lakhani of the Child Poverty Action Group describes how the new Child Support Agency will operate. PMID- 8491642 TI - No smoke without fire. PMID- 8491641 TI - Violence. Protect and survive. AB - Health visitors and other nurses working; often alone, in the community are particularly vulnerable to attack. Health service employers have a legal responsibility to protect the health and safety of employees at work. HVA health and safety representatives and/or local accredited representatives should ensure that employers have agreed procedures for protecting staff as far as possible from risk of violent attack and for reporting and following up violent incidents. PMID- 8491643 TI - Community healthcare week 1993. Marketing the message. PMID- 8491644 TI - Equal rights. PMID- 8491645 TI - Women's smoking: government targets and social trends. AB - Hilary Graham reviews the government's targets for a reduction in smoking prevalence among women in the light of the changing patterns of women's smoking. She argues that the targets can not be met unless both policy-makers and health professionals give greater attention to the links between women's smoking and the circumstances of women's lives. PMID- 8491647 TI - Curbing the death merchants. PMID- 8491646 TI - Gender, class and smoking cessation work. AB - Clare Blackburn argues that a understanding how smoking helps working class women to cope is vital to any intervention encouraging them to stop. Health visitors who are developing strategies to lessen the impact of material stresses on women are therefore key workers in smoking cessation programmes. PMID- 8491648 TI - Smoking and pregnancy: the role of health professionals. PMID- 8491649 TI - Youth and style magazines: hooked on smoking? PMID- 8491650 TI - Launching a national helpline. AB - Launched in October 1990, the National Asthma Campaign telephone helpline answered over 10,000 enquiries in its first 18 months of operation. Most callers were either parents of children with asthma or those with the condition themselves. STEVE CRONE et al describe the operation of the 'Asthma helpline' and the lessons learned about clients' concerns and information needs. PMID- 8491651 TI - Kissing the weed goodbye. AB - School nurses in Bath city organised a week-long stop-smoking campaign in senior schools to mark last year's national no smoking day in March. Their strategy was to appeal to pupils' pride and purses, as MARLENE GALLOP reports. PMID- 8491652 TI - Like lambs to the slaughter. PMID- 8491653 TI - Setting up a no smoking support group. AB - Smoking is the single greatest cause of ill-health and disability in the UK; some one million people die from smoking relating disease each year. It is a clear target for the health visitor's health promoting activities, argues Jayne McDermott. Here she describes setting up a successful 'No smoking' support group. PMID- 8491654 TI - Quality of life after coronary angioplasty. AB - OBJECTIVE: To explore the impact of percutaneous transluminal coronary angioplasty (PTCA) on perceived quality of life and health-related quality of life. DESIGN: One-group, pretest-posttest design. Pretest data were collected the evening before PTCA and posttest data were collected 4 to 6 weeks after PTCA. Data were collected from medical records, structured interview, and mailed questionnaire. SETTING: University-affiliated, Midwestern medical center. PATIENTS: Forty patients undergoing PTCA. OUTCOME MEASURES: Perceived quality of life was assessed by use of the Ferrans and Powers Quality of Life Index. Health related quality of life was assessed in terms of cardiac symptoms, tolerance of physical activity, exercise capacity, perceived general health, return to work, and lifestyle changes. INTERVENTION: PTCA. RESULTS: Perceived quality of life increased significantly due to increased satisfaction with health and functioning rather than changes in other areas of life. Significant improvements were found in cardiac symptoms (decreased incidence of chest pain and frequency of cardiac symptoms), tolerance of physical activity (decrease in symptoms with activity, increase in number of blocks able to walk, and decrease in interference with recreational activities because of symptoms), treadmill tests, and perceived general health. Regarding lifestyle changes, significant numbers of subjects quit smoking and increased their frequency of exercise, but the majority reported cheating on their prescribed diets. CONCLUSIONS: PTCA was found to result in significant improvements in perceived quality of life and health-related quality of life. PMID- 8491655 TI - Family satisfaction and affect of men and their wives after myocardial infarction. AB - OBJECTIVE: To describe (1) the affect of patients who have had a myocardial infarction and their spouses during hospitalization, (2) the correlation between patient and spouse on affect and satisfaction with family function, and (3) the relationship between satisfaction with family function and affect for both patient and spouse. DESIGN: Descriptive, correlational, cross-sectional. SETTING: Five hospitals in the Delaware Valley: four were community based and one was a university medical center. PATIENTS: Thirty-five couples who were married and living together. Patients were men with a diagnosis of myocardial infarction without renal, vascular, cerebral, or pulmonary complications who had been transferred from the cardiac care unit before being discharged. MEASURES: The patient completed the medical and demographic data form. Both patient and spouse completed the Family APGAR, a five-item questionnaire designed to give a rapid overview of satisfaction with the functional status of either a nuclear or alternative lifestyle family, and the Affects Balance Scale, a 40-item adjective mood scale that measures positive affect states, negative affect states, and the balance between them. RESULTS: Both patients and spouses experienced considerable negative affect and reduced positive affect during hospitalization when compared with the norms for nonclinical subjects. Patients and spouses were highly correlated on both measures, particularly for satisfaction with family function and positive affect (p < 0.01). Positive affect and satisfaction with family function were significantly positively correlated for spouses (p < 0.05). Additionally, it was found that both patients (p = 0.001) and spouses (p = 0.032) who were married longer were more satisfied with family function and that older patients reported more positive affect (p = 0.023). CONCLUSIONS: Both male patients who have had a myocardial infarction and their spouses experienced considerable emotional distress during hospitalization, with the implications that assessment should focus on the family unit as well as the individual and that interventions be directed toward emotional as well as physical symptomatology. The results of this study also suggest that female spouses with lower satisfaction with family function and younger male patients may be at greater risk for higher levels of negative affect. PMID- 8491656 TI - Cardiac retransplantation: determining limits. AB - OBJECTIVE: Cardiac transplantation has become an acceptable treatment option for end-stage congestive heart failure. Because of the increasing demand, there are not enough hearts to supply all patients in need of cardiac transplantation. This significant supply and demand imbalance necessitates that rationing decisions be made. This article will explore decisions made surrounding cardiac retransplantation. CONCLUSIONS: Early statistics suggest that survival for patients undergoing retransplantation is lower than first-time transplant recipients. In addition, the question of justice or fairness arises. Patients who are offered second and third heart transplants may deprive a significant number of patients who have not had their first chance at transplantation. The authors propose, based on medical suitability, respect for autonomy, and the principle of justice, that cardiac transplantation be a one-time treatment option. Retransplantation should not be allowed. PMID- 8491657 TI - Minimizing respiratory complications of nasoenteric tube feedings: state of the science. AB - This article summarizes research findings regarding ways to minimize the two most dreaded complications of tube feedings: (1) introduction of feedings through tubes positioned in the respiratory tract, and (2) pulmonary aspiration. Bedside methods that lack reliability in ruling out inadvertent respiratory placement of feeding tubes include the auscultatory method, the bubbling under water method, and observing for respiratory symptoms. Testing the pH of aspirates from feeding tubes can be of use in ruling out respiratory placement of newly inserted tubes when acidic values are properly obtained; further, this method can also be helpful in determining when a tube has migrated from the stomach to the intestine. Based on experience, the most frequently cited values for excessive gastric residuals are 100 to 150 ml. In a recent small study, researchers concluded that the residual volume that should raise concern in patients with nasogastric tubes is 200 ml and in patients with gastrostomy tubes the amount is 100 ml. Several recent studies indicate that although elevating the head of the bed 30 to 45 degrees does not prevent aspiration, it does reduce its frequency and severity. Because many studies described in this review have not been replicated, readiness of their findings for clinical application is variable. Many questions regarding methods to prevent respiratory complications in tube-fed patients remain unanswered, largely because it is difficult to design clinical studies with sufficient control of significant variables. PMID- 8491658 TI - Transbronchial intubation of the right pleural space: a rare complication of nasogastric intubation with a polyvinylchloride tube--a case study. AB - Inappropriate intubation of the tracheobronchial tree by a fine-bore nasogastric tube with a metal stylet is a well-known hazard. We report a pulmonary perforation and hydropneumothorax caused by a polyvinylchloride nasogastric tube without a stylet in a child of 13 months. The position of the tube was checked by auscultation before feeding. It would appear that the auscultatory method is inadequate in checking the correct placement of a nasogastric tube in young children. An ordinary nasogastric tube can cause pulmonary perforation. PMID- 8491659 TI - Disappearance of eosinophils from bronchoalveolar lavage fluid after patient education and high-dose inhaled corticosteroids: a case report. AB - Inhaled steroid therapy is being emphasized in the treatment of asthma but requires patient adherence to regular dosing regimens and skilled inhalation techniques for treatment to be effective. If used correctly, high-dose inhaled corticosteroids may eradicate specific types of inflammatory cells from the airway, whereas use of systemic corticosteroids in chronic asthma may not significantly reduce airway inflammation or clinical symptoms. We report a case in which reduction in inflammatory cells in the airway was confirmed by bronchoalveolar lavage after individual patient education, training in self monitoring, and treatment with inhaled corticosteroids. Clinical symptoms were reduced after conversion of this patient from systemic to inhaled corticosteroids. PMID- 8491660 TI - Critical care unit noise and rapid eye movement (REM) sleep. AB - OBJECTIVE: To determine if Critical Care Unit (CCU) sound levels suppress rapid eye movement (REM) sleep. DESIGN: Posttest-only control group experimental design. SETTING: Sleep laboratory located in a university neurologic institute. SUBJECTS: Seventy paid ($40) women who had no hearing or sleep problems. PROCEDURES: Subjects were randomly assigned to a noise or quiet (control) group while attempting to sleep overnight in the laboratory. Noise-condition subjects heard an audiotape recording of CCU nighttime sounds. The audiotape recording was withheld from the control group. RESULTS: Subjects in the noise condition showed poorer REM sleep on seven of 10 measures. These included REM activity and shorter REM durations throughout the night and during the first and second halves of the night as well as a longer interval between the first and second REM cycles. The majority of the t test results were significant at the 0.001 level or better. CONCLUSIONS: Although generalization of the results to CCU patients is limited (because of the use of laboratory subjects), the results provided convincing support for a causal relationship between CCU sound levels and suppression of REM sleep. PMID- 8491661 TI - Effect of intensive care simulation on anxiety of nursing students in the clinical ICU. AB - OBJECTIVE: To determine the effect of a campus critical care simulation on anxiety of nursing students in the clinical intensive care unit. DESIGN: Quasi experimental pretest-posttest design using a sample of convenience. SETTING: Large Midwestern university. SUBJECTS: Second semester, junior level nursing students enrolled in a generic baccalaureate nursing program. Students currently enrolled in an adult medical-nursing course with one allotted day for a campus critical care laboratory and a clinical day in affiliated community hospitals. OUTCOME MEASURES: Reduction in anxiety, as measured by the Spielberger State Trait Anxiety Inventory, related to psychomotor skill performance in a highly technological clinical setting. INTERVENTION: Campus critical care simulation laboratory, which provided time for information, demonstration, discussion, practice, and validation of performance skills associated with technology in a usual critical care setting. RESULTS: There was no significant difference in anxiety scores of subjects who received a campus critical care simulation before attending an actual clinical critical care experience versus those students who did not (t = 1.70, p = 0.094). There was no significant difference in anxiety scores of the experimental group after attending a campus simulation (t = 1.18, p = 0.250). Attending a campus critical care experience did not result in a decrease in critical care clinical setting anxiety. CONCLUSIONS: There are numerous reasons why students experience anxiety in the clinical setting, one of which is anxiety related to task performance. Although familiarity with psychomotor skills is beneficial, study findings indicate that familiarity with psychomotor skills is not sufficient to decrease anxiety in the critical care clinical setting. PMID- 8491662 TI - Thermodilution cardiac output determinations: a comparison of iced and refrigerated injectate temperatures in patients after cardiac surgery. AB - OBJECTIVE: To compare cardiac output determinations with two temperatures of injectate: iced (0 degrees to 6 degrees C) and refrigerated (10 degrees to 16 degrees C) in adult patients after cardiac surgery. DESIGN: A quasi-experimental study design was used. The dependent variable was cardiac output. The independent variable was injectate temperature. Each patient served as his or her own control. SETTING: Intensive care unit at a 500-bed urban teaching hospital in Western Canada. SAMPLE: A convenience sample of 40 male and female patients admitted to the intensive care unit after myocardial revascularization and/or valvular surgery between March and August 1991. All patients experienced surgery with the normothermic technique. METHOD: Each subject had cardiac output determinations performed within 12 hours of surgery with both 10 ml refrigerated and 10 ml iced injectate. The capped syringe technique was used. DATA ANALYSIS: A paired t test was performed to determine statistically significant differences between the two sets of measurements. Regression analysis was used to determine strength of agreement between the two techniques. Clinical significance was examined by a difference in mean cardiac output greater than 15% resulting in an alteration in medical therapy. RESULTS: There were no statistically or clinically significant differences between the two methods of cardiac output determinations. Regression analysis showed very good agreement (r = 0.965, p < 0.0001). Clinically, when the two cardiac outputs were reported to the surgeon, medical therapy was not altered based on differences. CONCLUSIONS: The use of 10 ml of refrigerated injectate provides reproducible cardiac output results as compared with iced injectate in normothermic patients after cardiac surgery. Further investigation is required to generalize these results to other patient populations and to determine the reproducibility with a lower volume of injectate. PMID- 8491663 TI - Hand-washing behavior versus hand-washing guidelines in the ICU. PMID- 8491664 TI - Spotlight article: pulse oximetry in the postoperative care of cardiac surgical patients: a randomized clinical trial. (Bierman MI, Stein KL, Snyder JV. Chest 1992; 102: 1367-70.). AB - Despite the limitations noted in this critique, the study provides information regarding the usefulness of pulse oximetry in care of postoperative cardiac surgery patients. Similar studies could be done with other groups of critically ill patients. Evaluation of technology in the critical care setting is essential so that care can be rendered in the safest and most efficient, cost-effective, manner. PMID- 8491666 TI - Amount of radiation that patients are receiving during their hospital stay. PMID- 8491665 TI - Xanthomonas maltophilia peritonitis in a patient undergoing peritoneal dialysis. PMID- 8491667 TI - Immunolocalization of manganese superoxide dismutase in normal and transgenic mice expressing the human enzyme. AB - The localization of manganese superoxide dismutase (MnSOD) was determined using immunohistochemistry of various tissues of normal and transgenic mice which express the human enzyme, with emphasis on studies of mouse kidney and lung. Mouse kidney and lung were studied using both frozen section analysis and paraffin sections following fixation in a variety of fixatives. Formalin fixation resulted in a loss of antigenicity, while fixation in zinc formalin or B5 fixative gave results similar to those from frozen sections. Immunoperoxidase studies using antibodies to MnSOD showed greater staining in transgenic kidney or lung than in identical tissues in normal mice when appropriate fixation was used. In contrast, equal immunostaining was obtained in kidney or lung from normal and transgenic mice when antibodies to catalase or copper zinc superoxide dismutase were utilized. Immunogold ultrastructural analysis of MnSOD localization for lung and kidney was also performed. As compared to normal mice, transgenic mice exhibited greater staining of the mitochondria of kidney interstitial fibroblasts and glomerular, endothelial, and smooth muscle cells. In the lungs of transgenic animals, all cells showed increased staining; smooth muscle cells demonstrated the most marked increase in immunolabelling. The results indicate that these transgenic mice overexpress MnSOD in their mitochondria, and that this occurs selectively in at least some mesenchymal tissues. PMID- 8491668 TI - Differences in erythropoiesis in normal chicken and quail embryos. AB - Using antibodies against the fetal and adult forms of alpha- and beta-globin, it has been shown that erythropoiesis in the para-aortic foci (PAF) constitutes a major species-specific difference between chicken and quail embryos. In quail embryos, para-aortic foci are rare, small and rather heterogeneous with regard to their erythropoietic and haemopoietic cell composition. In contrast, the PAFs in chicken embryos are abundant and consist of large numbers of erythropoietic cells. In both species a time difference (approximately 1 day) is observed between the first expression of the fetal alpha- and beta-globin and the adult alpha- and beta-globin in erythropoietic cells. Adult erythropoiesis in both species can be detected first in the stalk of the yolk sac; this is similar to the situation in mammalian and amphibian species. From this time onward the number of circulating adult erythrocytes increases steadily. Whereas in chicken, large intraembryonic foci that can serve as sources for these adult cells arise concomitantly, no such foci can be detected in quail embryos, suggesting that the quail yolk sac is a major source for these adult red blood cells. PMID- 8491669 TI - Detection of glycosaminoglycans on the surface of human umbilical vein endothelial cells using gold-conjugated poly-L-lysine with silver enhancement. AB - Endothelial glycosaminoglycans are important in a diverse range of vascular functions. In the course of a biochemical and histological study exploring the role of glycosaminoglycans in inflammation, we have investigated the use of gold conjugated poly-L-lysine with silver enhancement to establish the nature and physical location of glycosaminoglycans on the surface of cultured human umbilical vein endothelial cells. Cationic gold was effective in locating anionic sites in both cultured endothelial cells and in paraffin-embedded renal tissue. By manipulating pH, and by using enzymes specific for degrading glycosaminoglycans, it was found that, at pH 1.2, staining was directed primarily at glycosaminoglycans. The surface of human umbilical vein endothelial cells was found to be extensively covered in heparan sulphate, the histological appearance of which was dependent upon the fixation procedure employed. Heparan sulphate was also seen to co-distribute with the extracellular matrix protein, fibronectin, when endothelial cultures were simultaneously stained with cationic gold and an antibody to cellular fibronectin. PMID- 8491670 TI - In situ glucose-6-phosphate dehydrogenase activity during development of pre implantation mouse embryos. AB - Glucose-6-phosphate dehydrogenase activity was analysed cytophotometrically in oocytes and pre-implantation embryos of mice. A bimodal distribution pattern was not found. Therefore, female and male embryos could not be discriminated on the basis of linkage of the enzyme with the X-chromosome during the pre-implantation period. The dehydrogenase activity in ovulated eggs and pre-implantation embryos up to the 8-cell stage was 65% of that present in follicular oocytes. In morulae and blastulae, the activity was further decreased to a level that was only 10-20% of the activity present in oocytes. The dramatic decrease in dehydrogenase activity could not be explained by modulation of the enzyme molecules, because KM values did not vary strongly. It is unlikely that the abundant activity of glucose-6-phosphate dehydrogenase in oocytes is due to high activity of the pentose phosphate pathway because of the low activity of 6-phosphogluconate dehydrogenase, the next step in this pathway. It is concluded that high activity of glucose-6-phosphate dehydrogenase in oocytes is needed for keeping oocytes viable, and for generation of NADPH which is important for the fertilization process. PMID- 8491671 TI - Comparative immunohistolocalization of carbonic anhydrase isozymes I, II and III in the equine and bovine digestive tract. AB - Immunohistochemical localizations of carbonic anhydrase isozymes (CA-I, CA-II and CA-III) in equine and bovine digestive tracts were studied. In the horse, epithelial cells in both the oesophagus and non-glandular part of the stomach lacked all three isozymes. In contrast, surface epithelial and parietal cells in the glandular region of the stomach showed reactivity for CA-II. In the small intestine, absorptive columnar cells covering the villi in the duodenum were positive for CA-II. The epithelium of the jejunum and ileum lacked all three isozymes. In the large intestine, CA-II was detected in the columnar cells in the upper part of the crypt. In cattle, epithelial cells of the oesophagus showed reactions for CA-I and CA-III but not for CA-II. Although the absorptive epithelial cells of the small intestine lacked CA-I, CA-II and CA-III, those of the upper part of large intestine crypts were heavily stained for all three isozymes. PMID- 8491672 TI - Distribution of calcium in a subset of chronic hibernating myocardium in man. AB - The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis. PMID- 8491673 TI - Adenosine triphosphate-lead histochemical reactions in ependymal epithelia of murine brains do not represent calcium transport adenosine triphosphatase. AB - The strong enzyme histochemical reactions for adenosine triphosphatase (ATPase) seen in ependymal tanycytes after incubation in calcium-containing media have previously been reported as calcium transport ATPase. Investigation of these reactions showed that: (1) any nucleoside triphosphate can serve as a substrate; (2) diphosphates and monophosphates cannot replace triphosphates; this includes p nitrophenyl phosphate which is readily hydrolysed by plasma membrane transport ATPases; (3) strong localization occurs in the presence of millimolar concentrations of either calcium or magnesium ions; there is no absolute requirement for calcium ions; (4) they are not inhibited by sulphydryl inhibitors or calmodulin antagonists; (5) lead phosphate precipitates are localized almost entirely on the external face of tanycyte plasma membranes. In addition, the technique gives strong localization to vessels in the choroid plexus but not to the choroidal epithelium. Immunohistochemistry with a primary antibody raised against Ca2+, Mg2(+)-ATPase stains the choroidal epithelium but not the vessels or the ependymal tanycytes. These results are inconsistent with identification of the reaction as calcium transport ATPase but support characterization as an ecto ATPase. PMID- 8491674 TI - Cathepsin E in follicle associated epithelium of intestine and tonsils: localization to M cells and possible role in antigen processing. AB - A specific rabbit anti-human serum was used selectively to localize the aspartic proteinase cathepsin E to follicle associated epithelium (FAE) of human and rat intestine, including jejunum, ileum, appendix, colon and rectum, as well as of human palatine, pharyngeal and lingual tonsils. Coexpression of class II histocompatibility antigen HLA-DR antigen has been observed in some of the cathepsin E-positive epithelial cells. In addition, cathepsin E has been detected in a few mononuclear cells of intestinal lymphoid structures and tonsils resembling interdigitating reticulum cells of lymph nodes. Another aspartic proteinase, cathepsin D, has been found to be poorly represented in FAE and intensely expressed by macrophages. Electron immunocytochemistry localized cathepsin E to endosomal vesicles and endoplasmic reticulum of M cells in rat and human ileum as well as of M-like cells in human palatine tonsil. The results suggest a possible role of endosomal cathepsin E in the processing of macromolecules and microorganisms transported by M cells and related epithelial cells to mucosal associated lymphoid tissue (MALT). PMID- 8491675 TI - The innervation of the bovine ductus deferens: comparison of a modified acetylcholinesterase-reaction with immunoreactivities of cholinacetyltransferase and panneuronal markers. AB - The innervation pattern of the bovine deferent duct was studied by acetylcholinesterase (AChE)-histochemistry and by immunohistochemical methods. Using antibodies against protein gene product-9.5 (PGP-9.5) and neuron specific enolase (NSE) the complete innervation pattern can be visualized. Thick nerve bundles in the periductal connective tissue supply the two-layered muscular coat. The inner, mainly circularly arranged muscle bundles are innervated by a particularly dense plexus, whereas the nervous network of the more longitudinally running outer musculature is somewhat looser. Additionally, nerve fibres were observed in the subepithelial space in connection with blood vessels and in close proximity to the basal lamina. An innervation pattern analogous to that of the two panneuronal markers was displayed in the immunoreaction against dopamine-beta hydroxylase (DBH), indicating that the innervation of the bovine deferent duct is predominantly adrenergic. However, the positive reaction with a monoclonal antibody against cholinacetyltransferase (ChAT) specifically demonstrated for the first time the presence of a cholinergic nerve plexus, restricted to the inner muscular layer and the subepithelial space. A modified, direct-colouring AChE method is presented, which uses copper chloride as source of cupric ions, acetylthiocholine chloride as substrate and 2-morpholinoethanesulphonic acid (MES) as buffer. After short incubation (1-2 h) our modified method allows the specific visualization of cholinergic nerves, comparable to the results of ChAT immunoreactivity; following a long incubation time (24 h), it reliably illustrates the autonomous innervation pattern as completely as immunohistochemical panneuronal markers. PMID- 8491676 TI - Glomerular extracellular matrices and anionic sites in aging ddY mice: a morphometric study. AB - A morphometric study was undertaken to examine age-related changes in glomerular ultrastructure and anionic sites in ddY male mice at various ages. A progressive increase in glomerular extracellular matrices, including thickening of the glomerular basement membrane (GBM), formation of GBM nodules, and mesangial matrix increase, was found to be the primary age-related ultrastructural change in aging mice; there were also electron-dense deposits in mesangial and subepithelial regions. The extent of GBM thickening in mice was less than was reported in rats. Rather, the GBM nodules, which had the same electron density as the lamina densa (LD) and protruded on the subepithelial side of the GBM, were more striking. Quantitative evaluation showed that GBM thickness, number and size of GBM nodules, and the area of the mesangial matrix were significantly correlated with the age of the mice. The distribution of anionic sites in the glomeruli of aging animals was described for the first time. No statistically significant differences were noted between the number of glomerular anionic sites in the different age groups. These results indicate that the increase in glomerular extracellular matrices reported in aged rats was also present in aged mice, although the extent of various changes was different. The results also indicate that this increase in glomerular extracellular matrices with age was not accompanied by significant alteration in glomerular anionic sites. PMID- 8491677 TI - Twenty years follow-up of patients with inoperable cancer of the prostate (stage C) treated by radiotherapy: report of a national cooperative study. AB - PURPOSE: To evaluate the longevity and curability of patients with inoperable, Stage C, carcinomas of the prostate by means of external pelvic irradiation. METHODS AND MATERIALS: 372 patients, averaging 61 years of age, with histologically proven adenocarcinoma of the prostate, Stage C, received radiotherapy as part of a National Research Study, from 1967 to 1973. Treatments were administered in accordance with a strict protocol. Portals of entry were optional but it was required that the total dose received at the center of the prostate should be no less than 7000 cGy in no less than 47 days or 7500 cGy in 54 days. RESULTS: 245 of the 372 patients survived 5 years without evidence of recurrence of metastases; 142 were living after 10 years, 64 after 15 years, and 24 after 20 years. A total of 167 patients (44%) survived for years and died from intercurrent diseases without evidence of prostatic cancer. A total of 177 patients (47%) died of prostatic cancer in decreasing proportions in the years after treatment. Mild episodes of hematuria and of rectal bleeding were recorded in a number of patients; urethral and rectal strictured occurred following cystitis and proctitis but no life-threatening complications occurred. CONCLUSIONS: Adequately fractionated external pelvic irradiation can eradicate inoperable intrapelvic prostatic cancer. A simple statement of survival would disregard the fact that these elderly patients may be cured of cancer and yet may die of intercurrent diseases proper of their age. Also, it may be expected that a number of patients with Stage C may have unsuspected subclinical bone metastases when first seen and that death from metastases is not necessarily a reflection on the effectiveness of the regional treatment. PMID- 8491678 TI - Carcinoma of the prostate: results of radical radiotherapy (1970-1985). AB - PURPOSE: To determine the outcome and prognostic factors in patients with localized carcinoma of the prostate treated with external beam radiation therapy. METHODS AND MATERIALS: A retrospective review of 999 patients with histologically confirmed adenocarcinoma of the prostate treated radically with megavoltage irradiation at the Princess Margaret Hospital between 1970 and 1985. Prognostic factors were analyzed using recursive partitioning method. RESULTS: Overall survival at 5 and 10 years were 69.8% and 40.1% for the whole group. The cause specific survival rates were 78.9% and 53.5%, respectively. The cause-specific survival rates were significantly different at 10 years by T stage, T1 being 79.0%, T2 66.0%, T3 55% and T4 22%. The overall clinical local control rates was 77% in the first 5 years following treatment. There was no statistically significant difference in the local control rates of T1 and T2 stage disease at 5 years, the combined rate being 88%. Significant differences were observed between other stages, being 76% for T3 and 55% for T4. At 10 years the control rate for T1 tumours was maintained for T1 stage disease (92%) but was significantly reduced for other stages, T2 75%, T3 67% and for T4 37%. In the whole group 33.5% of patients had distant metastases in the first 5 years. The distant relapse rates at 10 years were significantly different by T stage, being 20% for T1, 33% for T2, 55% for T3 and 87% for T4. Multivariate analysis demonstrated that only T stage and histological grade were independent prognostic covariates for cause specific survival. Age was the only other independent variate in terms of overall survival. The late radiation related morbidity was 2.3% overall; 1.3% affecting rectum and recto-sigmoid and 1.0% arising in the bladder. CONCLUSION: In terms of survival the results of radiotherapy of intracapsular disease were excellent, but they were less satisfactory in patients with direct extracapsular extension. The assessment of local control was difficult and may have reflected more the lack of local disease progression rather than true local tumor control. The treatment was well tolerated and there were few serious late complications. PMID- 8491679 TI - Effect of split-course radiotherapy on survival and local control in advanced localized prostatic carcinoma. AB - PURPOSE: to analyze the effect of overall treatment time of radiotherapy on survival and local control in locally advanced prostatic cancer in a split-course treatment setting. METHODS AND MATERIALS: 168 patients with Stage C prostatic cancer treated during 1979-1989 by the split-course method where the overall treatment time is protracted. Treatment consisted of whole pelvis irradiation of 40 Gy in 4 weeks, followed by a planned 3-week interruption and an additional 26 Gy by the reduced field technique to a total dose of 66 Gy in 9 weeks and 30-33 fractions. The overall treatment time varied from 55 to 100 days. Thirty-eight percent (63) of the patients were treated primarily with radiotherapy, while the rest (105) had received androgen ablative therapy during 2 to 4.5 years before radiotherapy. To examine the effect of treatment time on local control, the patients were divided into three groups ( < or = 63 days, 64-70 days, and > 70 days) by treatment time. RESULTS: the 5-year actuarial survival rates, calculated from the date of diagnosis, were 91% for the hormonally manipulated patients and 69% for the patients treated with radiotherapy alone. The 5-year actuarial local control rates, counted from the start of radiotherapy, were 84% for radiotherapy and 80% for the hormonally manipulated group. Overall, no significant effect of treatment time could be seen, either for radiotherapy alone or for the hormonally manipulated group. The results were similar when the material was further divided by T category and histologic grade. CONCLUSIONS: no significant effect of overall treatment time (55 to 100 days) on survival or local control was found in either group. The survival time from diagnosis was longer in the hormonally pretreated group. Apparently, with adequate doses ( > or = 65 Gy) the overall treatment time becomes less important for local control of advanced prostatic cancer, even in a split-course treatment setting. PMID- 8491680 TI - Exclusive radiation therapy in endometrial carcinoma. AB - PURPOSE: From 1967 to 1986, 250 patients with endometrial carcinoma were treated with exclusive radiation therapy: 178 with a minimal follow-up of 5 years and 146 with a minimal follow-up of 10 years. The mean age was 68 years, ranging from 53 to 82 years, and the median follow-up duration was 8.5 years (minimum of 5 years and maximum of 23 years). METHODS AND MATERIALS: All the patients received an external beam radiation treatment (45 Gy in 4.5 to 5 weeks to the whole pelvis) followed by a utero-vaginal brachytherapy. RESULTS: At 5 years, the overall survival rate was 58.4% and the disease-free survival rate 55%. At 10 years the overall survival rate was 46.5% and the disease-free survival rate was 45.2%. Without considering deaths from intercurrent disease, the overall survival rate was 76.5% and the disease-free survival rate was 65.8% after 5 years, and 68% and 66%, respectively, after 10 years. The causes of failure were: isolated metastasis: 7.3%, local failure: 24.1% (4.5% with and 19.6% without concomittent distant metastasis). The rates of local control and of survival are related to the tumor stage and the tumor grade. CONCLUSION: The results are discussed according to the literature data and show the ability of exclusive radiation treatment to achieve acceptable results and to be a curative alternative for treating endometrial cancer providing that a correct external beam radiation therapy and a suitable brachytherapy are fulfilled. PMID- 8491681 TI - A retrospective study of the effects of pelvic irradiation for carcinoma of the cervix on gastrointestinal function. AB - PURPOSE: To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation. METHODS AND MATERIALS: Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers. RESULTS: Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p < 0.001) vitamin B12 (p < 0.01) and lactose (p < 0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p < 0.05) in those patients with lactose malabsorption. Gastric emptying (p < 0.01) and small intestinal transit (p < 0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p < 0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients. CONCLUSION: Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation. PMID- 8491682 TI - The treatment of 783 keloid scars by iridium 192 interstitial irradiation after surgical excision. AB - PURPOSE: the aim of this study is to confirm the effectiveness of irradiation associated with surgery in the treatment of keloids, to precise the factors favoring the recurrence of these keloids, and to evaluate the risk of recurrence, according to their initial distinctive features. METHODS AND MATERIALS: between 1977 and 1988, 544 patients, with a total of 855 keloids, were treated by interstitial radiotherapy immediately following total excision. RESULTS: recurrence rate is 21%, as against 50 to 80% for surgery alone, according to most authors. This recurrence rate is about the same as for external radiotherapy, but we prefer our method for practical reasons (cost, equipment, radiobiology, technique). Ninety percent of recurrences occurred in the year following therapy, which proves that a follow-up time of at least 12 months is needed for a study of keloids. In our experience, the keloids that are the most likely to recur are the largest and those giving rise to most symptoms. Bruising and loosened stitches, but in particular infection during therapy, largely favor a recurrence. In our series, the symptoms disappeared or were much improved in 80% of cases, and the cosmetic result was judged good by 75% of the patients. CONCLUSION: the results of this study proves the effectiveness of the method linking surgical excision and Iridium 192 interstitial irradiation and shows the importance of the sterile conditions of the treatment. PMID- 8491683 TI - Feasibility and toxicity of transrectal ultrasound hyperthermia in the treatment of locally advanced adenocarcinoma of the prostate. AB - PURPOSE: This Phase I trial tests the ability of a new hyperthermia device, the transrectal ultrasound probe, to heat the prostate gland, and evaluates the toxicity of transrectal ultrasound hyperthermia (TRUSH) given with concurrent standard external beam irradiation in the treatment of locally-advanced adenocarcinoma of the prostate. METHODS AND MATERIALS: Between June, 1990 and August, 1991, 14 patients with American Urological Society Stage C2 or D1 adenocarcinoma of the prostate were treated with TRUSH concurrently with standard external beam radiotherapy to the prostate. Twenty-two heat treatments were delivered in 14 patients; 8 patients received two TRUSH procedures, each separated by 1 week. Patient age ranged between 53-86 (mean: 72) years. Three patients had well-, 6 patients had moderately-, and 5 patients had poorly differentiated adenocarcinoma of the prostate. Karnofsky status ranged from 70 90. Standard radiotherapy to the prostate and periprostatic tissues was delivered using a four-field approach with 1.8-2 Gy daily fractions delivered 5 x/week to a total dose of 67-70 Gy calculated to the minimum tumor volume. TRUSH was delivered after transperineal placement of multipoint thermometry probes by a urologist, under transrectal ultrasound guidance. Two to three thermocouple probes containing seven sensors each were placed in the prostate in an attempt to sample temperatures throughout the gland. The sensor depth from the rectal wall ranged from 5-25 mm. RESULTS: Thirty-six percent of all sensors were heated above 42.5 degrees C averaged over 30 min; and all patients had at least some sensors within the prostate heated to temperatures > or = 42.5 degrees C. The average temperature of all sensors of all sensors (T(ave) +/- s.d.) over all treatments, however, was only 41.9 degrees C +/- 0.9 degrees C over 30 min. The maximum temperature for normal tissues outside the gland was 41.1 degrees C +/- 1.3 degrees C. Treatments have been well-tolerated with few complications. Tolerance has been "good" in 17/22, "fair" in 3/22, and "treatment limiting" in 2/22 treatments secondary to position intolerance and/or pain. There has been one episode of hypotension related to narcotic administration and three episodes of rapidly resolving pain during hyperthermia treatment. Mild hematuria has occurred in 5/22, and moderate hematuria has occurred in 2/22 transperineal thermometer catheter placements. CONCLUSION: In conclusion, TRUSH is well-tolerated and has great potential for consistently heating the prostate gland. We anticipate that further equipment modifications will improve our ability to heat the entire prostate to temperatures > 42.5 degrees C. PMID- 8491684 TI - Commissioning and quality assurance of treatment planning computers. AB - The process of radiation therapy is complex and involves many steps. At each step, comprehensive quality assurance procedures are required to ensure the safe and accurate delivery of a prescribed radiation dose. This report deals with a comprehensive commissioning and ongoing quality assurance program specifically for treatment planning computers. Detailed guidelines are provided under the following topics: (a) computer program and system documentation and user training, (b) sources of uncertainties and suggested tolerances, (c) initial system checks, (d) repeated system checks, (e) quality assurance through manual procedures, and in vivo dosimetry, and (f) some additional considerations including administration and manpower requirements. In the context of commercial computerized treatment planning systems, uncertainty estimates and achievable criteria of acceptability are presented for: (a) external photon beams, (b) electron beams, (c) brachytherapy, and (d) treatment machine setting calculations. Although these criteria of acceptability appear large, they approach the limit achievable with most of today's treatment planning systems. However, developers of new or improved dose calculation algorithms should strive for the goal recommended by the International Commission of Radiation Units and Measurements of 2% in relative dose accuracy in low dose gradients or 2 mm spatial accuracy in regions with high dose gradients. For brachytherapy, the aim should be 3% accuracy in dose at distances of 0.5 cm or more at any point for any radiation source. Details are provided for initial commissioning tests and follow up reproducibility tests. The final quality assurance for each patient is to perform an independent manual check of at least one point in the dose distributions, as well as the machine setting calculation. As a check of the overall treatment planning process, in vivo dosimetry should be performed on a select number of patients. PMID- 8491685 TI - Rapid vascular escape of arterially injected 16 alpha-radioiodo,17 beta estradiol. AB - PURPOSE: We undertook this study because confirmation of a rapid vascular escape and slow release back into the circulatory system suggests that arterial injection of radiohalogenated steroid receptor ligands might provide an efficacious route of administration for imaging or treatment of receptor-rich malignant tumors in peripheral tissues. METHODS AND MATERIALS: We injected radiolabeled 16 alpha-iodo,17 beta-estradiol ([I]-E), an estrogen receptor ligand, into the femoral artery of swine in a solution that contained [125I]-E in a known ratio to [99mTc]-labeled red blood cells. Fractions of femoral venous blood were collected at short intervals during 10 min. We looked for changes in the ratio of the radiolabels. [99mTc]-labeled red blood cells are known to remain in the vascular system for an hour or more. RESULTS: After passage of the injectate through the capillary bed of the swine leg, a dramatic decrease of the initial 125I:99mTc ratio to only 10% was observed in the femoral venous blood. This ratio increased gradually during the next 10 min to approximately 30% of that in the injectate, indicating that a significant portion (approximately 90%) of the [125I]-E was initially trapped in the limb and then slowly re-entered the vascular system. To obtain visual confirmation of the rapid vascular escape of iodo-estrogen, we injected either an imageable form of [I]-E (123I]-E) or [99mTc] labeled red blood cells into the dorsal aorta of superovulated rabbits, whose smaller size allowed whole-body imaging. The biodistributions of these radiopharmaceuticals were surveyed continuously by real-time planar gamma imaging. Within 2 min after the injection of [123I]-E, the outlines of the circulatory system were entirely lost; however, some estrogen receptor-rich tissues (the ovaries) as well as some non-target tissues, for example, the lower leg extremities, yielded well-defined images. In contrast, after intra-arterial injection of [99mTc]-labeled red blood cells, the circulatory system remained sharply defined for the duration of the study (40 min). CONCLUSION: A large fraction of [I]-E escapes from the vascular system during the first pass through an organ or limb, without regard to the estrogen receptor content of the tissue. PMID- 8491686 TI - Charged particle irradiation of sacral chordomas. AB - PURPOSE: The purpose of this report is determine the impact of charged particle irradiation at Lawrence Berkeley Laboratory (LBL) in treating patients with sacral chordomas. Overall survival, local control, complications, and predictive parameters are analyzed. METHODS AND MATERIALS: Fourteen patients with sacral chordomas were treated with the charged particles helium and neon between 1977 and 1989. The median dose was 7565 cGyE and the median follow up is 5 years. All patients were treated post-operatively; ten had gross residual disease. RESULTS: Kaplan-Meier survival at 5 years is 85%. Overall 5-year local control is 55%. A trend to improved local control at 5 years was seen in patients treated with neon when compared to patients treated with helium (62% vs 34%), in patients following complete resection versus patients with gross residual tumor (75% vs 40%), and in patients who had treatment courses under 73 days (61% vs 21%). Distant metastases were seen in two patients (14%). No patient developed neurologic sequelae or pain syndromes. One previously irradiated patient required colostomy, one patient had delayed wound healing following a negative post-radiation biopsy, and one patient developed a second malignancy. There were no genitourinary complications. CONCLUSION: Our experience indicates that post-operative charged particle irradiation of sacral chordomas appears to result in reasonable local control and survival with acceptable risk, and that additional evaluation on the use of heavy charged particles is warranted. PMID- 8491687 TI - Radiation therapy for giant cell tumor of bone. AB - PURPOSE: Giant cell tumor of bone is usually treated with surgical curettage. For recurrent tumors, tumors that are inoperable because of location, and tumors that would require amputation or another radical procedure limiting function, does radiotherapy provide an alternative for local control? METHODS AND MATERIALS: Sixteen patients with histologically confirmed, giant cell tumor of bone were treated at the University of Florida with irradiation between March 1973 and September 1988. Minimum follow-up was 32 months; 63% of the patients had follow up for at least 5 years, 44% for greater than 10 years. All sites received doses of 35 Gy or more, and all were treated with megavoltage irradiation. RESULTS: In 12 (75%) of 16 patients, the tumor was controlled locally with irradiation. The four failures occurred at 8, 13, 13, and 25 months following initiation of treatment. Surgical salvage was successful in all four failures for an overall local control rate of 100%. One patient developed pulmonary metastasis 1 month after surgical salvage and is alive without evidence of disease after multiple courses of chemotherapy, surgical resection, and whole-lung irradiation. All patients tolerated the treatment well with no severe or chronic complications. No secondary soft-tissue sarcomas have occurred within the irradiated areas. CONCLUSION: Giant cell tumor of bone is not a radioresistant tumor as once believed, and complications seen with modern treatment regimens are minor. PMID- 8491688 TI - Static and dynamic vascular impact of large artery irradiation. AB - PURPOSE: To evaluate functional post-radiotherapy arterial change in a select patient population. METHODS AND MATERIALS: Thirty-five seminoma patients were identified in the Radiation Oncology departmental records at Indiana University Medical Center. In this group the ipsilateral pelvis is treated with the contralateral pelvis available for evaluation as a matched control. Additionally, this group is generally young and unlikely to have pre-existing vascular disease, and shows excellent radiocurability with historically standard radiotherapy. Nineteen patients volunteered for a noninvasive vascular evaluation which included: Doppler ultrasound, segmental leg pressures, pulse volume recordings, and post-exercise testing. Average age at treatment was 36 (range 14-68) with an average follow-up of 8.8 years (range 1-20) with five patients now over 15 years post-treatment. The majority of the patients received 2500-2600 cGy. RESULTS: Three of 19 patients had abnormal vascular evaluations. Of these, two had bilateral abnormalities not felt to be solely associated with irradiation. The remaining patient showed both resting and post-exercise ipsilateral vascular abnormalities. Irradiation was the only identifiable etiologic agent for this patient's vascular abnormality. CONCLUSION: Subclinical vascular change attributable to low dose radiotherapy was identified in one of 19 patients (5%). Considering the radiocurability of seminoma patients this incidence is acceptable. In light of this slight, yet documented, arterial abnormality occurring with low dose radiotherapy, we recommend additional study of high dose radiotherapy patients to determine the incidence and morbidity of radiation induced arteriopathy in this group. PMID- 8491689 TI - Development of a second-generation fiber-optic on-line image verification system. AB - PURPOSE: We have previously reported the development of a fiber-optic fluoroscopic system for on-line imaging on radiation therapy machines with beam stops because of space limitation. While the images were adequate for clinical purposes in most cases, an undesirable grid artifact existed and distracted visualization. The resolving power of the system, limited by the 1.6 mm x 1.6 mm dimension of the input fibers, appeared insufficient in some cases. This work identifies solutions to reduce grid artifact and to improve the resolution of the system. METHODS AND MATERIALS: In the clinical system, it was found that the scanning mechanism of the newvicon camera was deflected differently at various gantry positions because of the different orientation of the earth's magnetic field. The small image misregistration produced grid artifact during image normalization, particularly near boundaries of the fiber bundles. One approach taken to reduce magnetic field effects was to shield the camera with mu-metal. Alternatively, a charged-coupled-device camera was used instead of the newvicon camera. As for improving spatial resolution, fibers with smaller input dimension were used. A 20 cm x 20 cm high resolution fiber-optic prototype consisting of 250 x 250 fibers, each with an input dimension of 0.8 mm x 0.8 mm was constructed. Its performance was tested using several phantoms studies. RESULTS: Both shielding the newvicon camera with mu-metal or replacing it with a charge coupled-device camera reduced grid artifact. However, optimal shielding could not be made for our clinical system because of the space limitation of its housing. High contrast resolution was improved, the 30% value of the modulation transfer function occurred at 0.3 linepairs per mm for the clinical system and at 0.7 linepairs per mm for the high-resolution prototype. However, because of the larger degree of transmission non-uniformity of the prototype, it was less effective using the current setup in detecting low contrast objects. CONCLUSIONS: The results are encouraging and demonstrate successful reduction of grid artifact and improvement of high contrast spatial resolution using the proposed methods. The less effective low contrast detection was related to reduced light collection efficiency due to use of prototype fibers whose productions were not closely monitored. The findings are being considered in our construction of a second generation clinical fiber-optic on-line image verification system. PMID- 8491690 TI - Objective evaluation of 3-D radiation treatment plans: a decision-analytic tool incorporating treatment preferences of radiation oncologists. AB - PURPOSE: Selecting the optimal radiation treatment plan from a set of competing plans involves making trade-offs among the doses delivered to the target volumes and normal tissues by the competing plans. Evaluation of 3-dimensional radiation treatment plans is difficult because it requires the review of vast amount of graphical and numerical data. We have developed an objective plan-ranking model based on the concepts of decision analysis. METHODS AND MATERIALS: Our model ranks a set of tentative radiation treatment plans from best to worst. A figure of merit is computed for each plan based on probabilities of possible clinical complications such as non-eradication of the tumor and radiation induced damage to the nearby healthy normal tissues, and weights which indicate their clinical relevance. This figure of merit is used to rank the plans. Key issues addressed by the model include the incorporation of individual treatment preferences of the radiation oncologist and clinical features of the patient. RESULTS: A methodology has been established for eliciting the treatment preferences of radiation oncologists. Results of this elicitation, and examples of several plan evaluations are presented. An interactive computer-based tool has been developed as one of a set of tools to assist in the evaluation of 3-dimensional radiation treatment plans. CONCLUSION: The paper presents a decision-analytic model incorporating radiation oncologists' treatment preferences and an interactive computer-based tool for objectively ranking competing radiation treatment plans. The tool can be used by radiation oncologists for the evaluation of competing plans, or as part of a system which tries to automatically generate optimal treatment plans using mathematical or symbolic techniques. PMID- 8491691 TI - Rectal thermoluminescent dosimeter measurements using the MicroSelectron High Dose Rate afterloader in postoperative intravaginal radiation cases. AB - PURPOSE: The purpose of this study is twofold: First, to measure the dose distribution along the anterior and posterior rectal wall, compare them to the prescribed dose and establish the rectal length receiving the maximum dose. Second, to carry out in-phantom dose measurements in order to confirm that the dose planned is in fact the dose delivered. METHODS AND MATERIALS: The dose distribution along the anterior and posterior rectal wall was measured for a group of 25 Gynecologic cases treated with a vaginal cylinder, using the MicroSelectron High Dose Rate system. The method of measurement employed flexible vinyl rectal probes (1 or 2 cm diameter). Two fine plastic tubes, each containing 15 Thermo Luminescent Dosimeters rods, were attached along the probe on opposite sides to measure the anterior and posterior rectal wall dose distributions. RESULTS: The dose distribution exhibited a sharp peak covering a rectal length from one to two centimeters. The peak doses for the anterior rectal wall ranged from 60% to 110% of prescribed dose. In-phantom measurements used layers of phantom material that contained a special source tube for the Iridium-192 source as well as Thermoluminescent Dosimeter tube(s) positioned at 1 cm distance from the source tube. The afterloader was programmed to deliver 300 cGy at 1 cm along its treatment length. CONCLUSION: The Thermo Luminescent Dosimeters measurements showed good agreement with the doses expected on the basis of the treatment plan. PMID- 8491692 TI - A template for rigid stereotaxic afterloading brachytherapy of the brain. AB - PURPOSE: This paper describes a system for the implantation of rigid stainless steel afterloading tubes into the brain using a stereotaxic head frame for both localization and treatment. METHODS AND MATERIALS: The stereotaxic frame is attached to the skull throughout the treatment, and the afterloading tubes are both rigid and fixed to the frame. The source positions are therefore fixed relative to the skull throughout the irradiation. Design and construction of templates, afterloading tubes and clamps are discussed in detail. RESULTS: The rigidity of the resulting implant provides accurate and immobile positioning of the planned isodose distribution relative to the defined treatment volume and makes it possible to carefully and rapidly plan a source loading which will best cover the volume of interest. The source template is not in contact with the patient at any time. The afterloading tubes are held strictly parallel during treatment, allowing for rapid and versatile preplanning prior to surgical placement. Placement options are enhanced by using a set of rotating templates. CONCLUSION: This system has been used for over 60 procedures without any mechanical or safety problems and has provided a significant improvement in both the speed and confidence of localization and treatment planning. There are significant advantages of such a system for High Dose Rate Afterloading Brachytherapy. PMID- 8491693 TI - Why shorter half-times of repair lead to greater damage in pulsed brachytherapy. AB - PURPOSE: Pulsed Brachytherapy consists of replacing continuous irradiation at low dose-rate with a series of medium dose-rate fractions in the same overall time and to the same total dose. For example, pulses of 1 Gy given every 2 hr or 2 Gy given every 4 hr would deliver the same 70 Gy in 140 hr as continuous irradiation at 0.5 Gy/hr. If higher dose-rates are used, even with gaps between the pulses, the biological effects are always greater. Provided that dose rates in the pulse do not exceed 3 Gy/hr, and provided that pulses are given as often as every 2 hr, the inevitable increases of biological effect are no larger than a few percent (of biologically effective dose or extrapolated response dose). However, these increases are more likely to exceed 10% (and thus become clinically significant) if the half-time of repair of sublethal damage is short (less than 1 hr) rather than long. This somewhat unexpected finding is explained in detail here. METHODS AND MATERIALS: The rise and fall of Biologically Effective Dose (and hence of Relative Effectiveness, for a constant dose in each pulse) is calculated during and after single pulses, assuming a range of values of T1/2, the half-time of sublethal damage repair. The area under each curve is proportional to Biologically Effective Dose and therefore to log cell kill. RESULTS: Pulses at 3 Gy/hr do yield greater biological effect (dose x integrated Relative Effectiveness) than lower dose-rate pulses or continuous irradiation at 0.5 Gy/hr. The contrast is greater for the short T1/2 of 0.5 hr than for the longer T1/2 of 1.5 hr. CONCLUSION: More biological damage will be done (compared with traditional low dose rate brachytherapy) in tissues with short T1/2 (0.1-1 hr) than in tissues with longer T1/2 values. PMID- 8491694 TI - Concerning the inferior portion of the spinal radiotherapy field for malignancies that disseminate via the cerebrospinal fluid. AB - PURPOSE: Many radiotherapists widen the inferior aspect of the craniospinal irradiation field to encompass the sacroiliac joints and "cover the sacral nerve roots." This is commonly referred to as a "spade" field. Other therapists, however, reject the notion of widening the bottom of the field--feeling that straight field borders are adequate. We have evaluated this controversy by an anatomical study. METHODS AND MATERIALS: Twenty-five skeletons were measured to ascertain the distance between the outermost portions of the posterior pedicles of L3, L4, and L5; the distance between the outermost portions of the intervertebral foramina between L3-L4, L4-5, and L5-S1 through which the spinal nerves pass; and the width of the most lateral portions of the posterior and anterior foramina of S1 and S2 through which the sacral spinal nerves would pass. Twenty-two cranial spinal irradiation simulator films of patients with medulloblastoma were used to measure the distance between the outermost portions of the posterior pedicles of L3, L4, and L5 and the foramina of S1 and S2. These measurements were then corrected for film magnification. RESULTS: Skeleton measurements showed that the mean width between the outer portions of the posterior pedicles of L3 and 4.1 cm, for L4 it was 4.4 cm, and for L5 it was 5.1 cm. Measurements of the mean maximum width of the intervertebral foramen for nerve root exit at the bottom of L3 was 4.1 cm, for L4 4.4 cm, and for L5 4.7 cm. The mean distance between the outermost portions of the intervertebral foramen for nerve root exit at the front of S1 was 5.9 cm while it was 5.0 cm for the back of S1. The mean distance between the outermost portions of the anterior foramen of S2 was 5.7 cm and 4.8 cm for the back. Measurements from the 22 simulation films show that the mean maximum width between the outer portion of the posterior pedicles of L3 was 3.3 cm, for L4 3.5 cm, and for L5 3.8 cm. The mean maximum width of the intervertebral foramen for nerve root exit at the bottom of S1 was 4.4 cm and 4.5 cm for S2. CONCLUSIONS: While the caudal end of the craniospinal field needs to be widened by 1.2 to 1.8 cm to encompass the increase in distance between nerve root exits as one moves inferiorly down the spine, coverage of the sacroiliac joints is not necessary. PMID- 8491695 TI - Incomparable report of clinical trial for locally advanced carcinoma of the prostate. PMID- 8491696 TI - Conventional external beam radiation therapy for prostatic cancer: where do we go from here? PMID- 8491697 TI - Prostate cancer: hot, but hot enough? PMID- 8491698 TI - Comments on: Commissioning and quality assurance of treatment planning computers. PMID- 8491699 TI - Is acetyl phosphate a global signal in Escherichia coli? PMID- 8491700 TI - Identification of a segment of the Escherichia coli Tsx protein that functions as a bacteriophage receptor area. AB - The Escherichia coli outer membrane protein Tsx functions as a nucleoside specific channel and serves as the receptor for colicin K and a number of T-even type bacteriophages, including phage T6. To identify those segments of the Tsx protein that are important for its phage receptor function, we devised a selection and screening procedure which allowed us to isolate phage-resistant strains synthesizing normal amounts of Tsx. Three different Tsx-specific phages (T6, Ox1, and H3) were employed for the selection of phage-resistant derivatives of a strain expressing a tsx(+)-lacZ+ operon fusion, and 28 tsx mutants with impaired phage receptor function were characterized. Regardless of the Tsx specific phage used for the initial mutant selection, cross-resistance against a set of six different Tsx phages invariably occurred. With one exception, these mutant Tsx proteins could still serve as a colicin K receptor. DNA sequence analysis of 10 mutant tsx genes revealed the presence of four distinct tsx alleles: two point mutations, an 18-bp deletion, and a 27-bp tandem duplication. In three isolates, Asn-249 was replaced by a Lys residue (tsx-504), and in four others, residue Asn-254 was replaced by Lys (tsx-505). The deletion (tsx-506; one isolate) removed six amino acids (residue 239 to residue 244) from the 272 residue Tsx polypeptide chain, and the DNA duplication (tsx-507; two isolates) resulted in the addition of nine extra amino acids (residue 229 to residue 237) to the Tsx protein. In contrast to the wild-type Tsx protein and the other mutant Tsx proteins the Tsx-507 protein was cleaved by trypsin when intact cells were treated with this protease. The Tsx proteins encoded by the four tsx alleles still functioned in deoxyadenosine uptake in vivo, demonstrating that their nucleoside-specific channel activity was not affected by the alterations that caused the loss of their phage receptor function. HTe changes in the Tsx polypeptide that confer resistance against the Tsx-specific phages are clustered in a small region near the carboxy terminus of Tsx. Our results are discussed in terms of a model for the topological organization of the carboxy-terminal end of the Tsx protein within the outer membrane. PMID- 8491701 TI - Sequence-based differentiation of strains in the Mycobacterium avium complex. AB - The complete 16S-23S rDNA internal transcribed spacer (ITS) was sequenced in 35 reference strains of the Mycobacterium avium complex. Twelve distinct ITS sequences were obtained, each of which defined a "sequevar"; a sequevar consists of the strain or strains which have a particular sequence. ITS sequences were identified which corresponded to M. avium (16 strains, four ITS sequevars) and Mycobacterium intracellulare (12 strains, one ITS sequevars). The other seven M. avium complex strains had ITS sequences which varied greatly from those of M. avium and M. intracellulare and from each other. The 16S-23S rDNA ITS was much more variable than 16S rDNA, which is widely used for genus and species identification. Phylogenetic trees based on the ITS were compatible with those based on 16S rDNA but were more detailed and had longer branches. The results of ITS sequencing were consistent with the results of hybridization with M. avium and M. intracellulare probes (Gen-Probe) for 30 of 31 strains tested. Serologic testing correlated poorly with ITS sequencing. Strains with the same sequence were different serovars, and those of the same serovar had different sequences. Sequencing of the 16S-23S rDNA ITS should be useful for species and strain differentiation for a wide variety of bacteria and should be applicable to studies of epidemiology, diagnosis, virulence, and taxonomy. PMID- 8491702 TI - Characterization and symbiotic importance of acidic extracellular polysaccharides of Rhizobium sp. strain GRH2 isolated from acacia nodules. AB - Rhizobium sp. wild-type strain GRH2 was originally isolated from root nodules of the leguminous tree Acacia cyanophylla and has a broad host range which includes herbaceous legumes, e.g., Trifolium spp. We examined the extracellular exopolysaccharides (EPSs) produced by strain GRH2 and found three independent glycosidic structures: a high-molecular-weight acidic heteropolysaccharide which is very similar to the acidic EPS produced by Rhizobium leguminosarum biovar trifolii ANU843, a low-molecular-weight native heterooligosaccharide resembling a dimer of the repeat unit of the high-molecular-weight EPS, and low-molecular weight neutral beta (1,2)-glucans. A Tn5 insertion mutant derivative of GRH2 (exo 57) that fails to form acidic heteropolysaccharides was obtained. This Exo- mutant formed nitrogen-fixing nodules on Acacia plants but infected a smaller proportion of cells in the central zone of the nodules than did wild-type GRH2. In addition, the exo-57 mutant failed to nodulate several herbaceous legume hosts that are nodulated by wild-type strain GRH2. PMID- 8491703 TI - Cloning, expression, and characterization of the icd gene in the immI operon of bacteriophage P1. AB - The immI operon of P1 contains the genes c4, icd (formerly called orfx), and ant which are constitutively transcribed in that order from a single promoter, P51b. C4 is an antisense RNA which is processed from the precursor transcript. C4 RNA acts as a translational repressor of icd, thereby also inhibiting antirepressor (ant) synthesis. We have cloned the icd and the overlapping icd and ant genes. We show, by means of plasmid deletion analysis, that icd is translationally coupled to ant. An internal in-frame deletion of icd making up 65% of the codons still allows antirepressor synthesis at a reduced rate, indicating that a functionally active icd gene product is dispensable for ant expression. We identify the product of the icd gene as a 7.3-kDa protein which interferes with cell division. The results suggest that constitutive expression of icd, in the absence of a functionally active antirepressor, prevents P1 lysogen formation because of its detrimental effect on the host cell. PMID- 8491704 TI - Enhanced thermotolerance and temperature-induced changes in protein composition in the hyperthermophilic archaeon ES4. AB - The hyperthermophilic archaeon ES4, a heterotrophic sulfur reducer isolated from a deep-sea hydrothermal vent, is capable of protecting itself from thermal stress at temperatures above its optimum for growth. The thermotolerance of ES4 was determined by exposing log-phase cells to various lethal high temperatures. When ES4 was shifted from 95 to 102 degrees C, it displayed recovery from an exponential rate of death, followed by transient thermotolerance. When ES4 was shifted directly from 95 to either 105 or 108 degrees C, only exponential death occurred. However, a shift from 95 to 105 degrees C with an intermediate incubation at 102 degrees C also gave ES4 transient thermotolerance to 105 degrees C. The protein composition of ES4 was examined at temperatures ranging from 75 to 102 degrees C by one-dimensional electrophoresis. Two proteins with molecular masses of approximately 90 and 150 kDa significantly decreased in abundance with increasing growth temperature, while a 98-kDa protein, present at very low levels at normal growth temperatures (76 to 99 degrees C), was more abundant at higher temperatures. The enhanced tolerance to hyperthermal conditions after a mild hyperthermal exposure and the increased abundance of the 98-kDa protein at above-optimal temperatures imply that ES4 is capable of a heat shock-like response previously unseen in hyperthermophilic archaea. PMID- 8491705 TI - Cloning and sequencing of the low-affinity penicillin-binding protein 3r-encoding gene of Enterococcus hirae S185: modular design and structural organization of the protein. AB - The clinical isolate Enterococcus hirae S185 has a peculiar mode of resistance to penicillin in that it possesses two low-affinity penicillin-binding proteins (PBPs): the 71-kDa PBP5, also found in other enterococci, and the 77-kDa PBP3r. The two PBPs have the same low affinity for the drug and are immunochemically related to each other. The PBP3r-encoding gene has been cloned and sequenced, and the derived amino acid sequence has been compared by computer-assisted hydrophobic cluster analysis with that of the low-affinity PBP5 of E. hirae R40, the low-affinity PBP2' of Staphylococcus aureus, and the PBP2 of Escherichia coli used as the standard of reference of the high-M(r) PBPs of class B. On the basis of the shapes, sizes, and distributions of the hydrophobic and nonhydrophobic clusters along the sequences and the linear amino acid alignments derived from this analysis, the dyad PBP3r-PBP5 has an identity index of 78.5%, the triad PBP3r-PBP5-PBP2' has an identity index of 29%, and the tetrad PBP3r-PBP5-PBP2' PBP2 (of E. coli) has an identity index of 13%. In spite of this divergence, the low-affinity PBPs are of identical modular design and possess the nine amino acid groupings (boxes) typical of the N-terminal and C-terminal domains of the high M(r) PBPs of class B. At variance with the latter PBPs, however, the low-affinity PBPs have an additional approximately 110-amino-acid polypeptide stretch that is inserted between the amino end of the N-terminal domain and the carboxy end of the membrane anchor. While the enterococcal PBP5 gene is chromosome borne, the PBP3r gene appears to be physically linked to the erm gene, which confers resistance to erythromycin and is known to be plasmid borne in almost all the Streptococcus spp. examined. PMID- 8491706 TI - Sterol composition of yeast organelle membranes and subcellular distribution of enzymes involved in sterol metabolism. AB - Organelles of the yeast Saccharomyces cerevisiae were isolated and analyzed for sterol composition and the activity of three enzymes involved in sterol metabolism. The plasma membrane and secretory vesicles, the fractions with the highest sterol contents, contain ergosterol as the major sterol. In other subcellular membranes, which exhibit lower sterol contents, intermediates of the sterol biosynthetic pathway were found at higher percentages. Lipid particles contain, in addition to ergosterol, large amounts of zymosterol, fecosterol, and episterol. These sterols are present esterified with long-chain fatty acids in this subcellular compartment, which also harbors practically all of the triacylglycerols present in the cell but very little phospholipids and proteins. Sterol delta 24-methyltransferase, an enzyme that catalyzes one of the late steps in sterol biosynthesis, was localized almost exclusively in lipid particles. Steryl ester formation is a microsomal process, whereas steryl ester hydrolysis occurs in the plasma membrane and in secretory vesicles. The fact that synthesis, storage, and hydrolysis of steryl esters occur in different subcellular compartments gives rise to the view that ergosteryl esters of lipid particles might serve as intermediates for the supply of ergosterol from internal membranes to the plasma membrane. PMID- 8491707 TI - Purification and characterization of an oxygen-labile, NAD-dependent alcohol dehydrogenase from Desulfovibrio gigas. AB - A NAD-dependent, oxygen-labile alcohol dehydrogenase was purified from Desulfovibrio gigas. It was decameric, with subunits of M(r) 43,000. The best substrates were ethanol (Km, 0.15 mM) and 1-propanol (Km, 0.28 mM). N-terminal amino acid sequence analysis showed that the enzyme belongs to the same family of alcohol dehydrogenases as Zymomonas mobilis ADH2 and Bacillus methanolicus MDH. PMID- 8491708 TI - Analysis of a genomic DNA region from the cyanobacterium Synechococcus sp. strain PCC7942 involved in carboxysome assembly and function. AB - We report on the sequencing and analysis of a 3,557-bp genomic DNA clone that is located between 4.8 and 1.2 kilobase pairs (kb) upstream of the rbcL gene and is capable of complementing a class of cyanobacterium Synechococcus sp. strain PCC7942 mutants requiring a high level of CO2. The upstream 2,704 bp of this sequence is novel, the remaining 852 bp having been reported by other workers. Four new open reading frames (ORFs) have been identified along with putative promoter elements. These ORFs, which could code for proteins of 7, 10.9, 11, and 58 kDa in size, have been named ORF 64, ccmK, ccmL, and ccmM, respectively. The last three have been named ccm genes on the basis that insertional mutagenesis of each produces a phenotype requiring a high level of CO2 (i.e., each produces a lesion in the CO2 concentrating mechanism). The putative gene product for the large ccmM ORF has three internally repeated regions and also has two possible DNA binding motifs. Two defined mutants in the 3,557-bp region, mutants PVU and P N, have been more fully characterized. The PVU mutant has a drug marker inserted into the ccmL gene, and it possesses abnormal rod-shaped carboxysomes. The P-N mutant is a 2.64-kb deletion of DNA from the same position in ccmL to a region closer to rbcL. This mutant, which has previously been shown to lack carboxysomes and have soluble ribulosebiphosphate carboxylase/oxygenase activity, has now been shown to have a predominantly soluble carboxysomal carbonic anhydrase activity. Both mutants were found to possess carboxysomal carbonic anhydrase activities which are below wild-type levels, and in the P-N mutant this activity appears to be unstable. The results are discussed in terms of the possible interactions of putative ccm gene products in the process of carboxysome assembly and function. PMID- 8491709 TI - Similar organization of the nusA-infB operon in Bacillus subtilis and Escherichia coli. AB - We reported previously the cloning and sequence of the Bacillus subtilis infB gene which encodes the essential IF2 factor required for initiation of translation (K. Shazand, J. Tucker, R. Chiang, K. Stansmore, H. U. Sperling Petersen, M. Grunberg-Manago, J. C. Rabinowitz, and T. Leighton, J. Bacteriol. 172:2675-2687, 1990). The location of the 5' border of the infB operon was investigated by using integrative plasmids carrying various DNA fragments from the region upstream of the infB gene. The lethal effect of disruption of the infB transcriptional unit could be suppressed when the integrated plasmid introduced the spac promoter upstream of the infB operon and transformants were selected in conditions of induction of spac expression. Such an integrated plasmid was used as a starting point to clone the promoter of the infB operon. Primer extension mapping suggests that a single sigma A-type promoter controls transcription of the infB operon. The sequence of a 5,760-bp region encompassing the infB gene was determined. The infB operon is located immediately downstream of the polC gene and comprises seven open reading frames, four of which appear to be the homologs of genes present in the same order in the Escherichia coli infB operon, including nusA. The striking similarity between the E. coli and B. subtilis infB operons suggests that the function of each gene pair is conserved and that the B. subtilis NusA homolog, which is 124 residues shorter than its E. coli counterpart, could play a role similar to its role in E. coli. PMID- 8491710 TI - Overexpression of the MarA positive regulator is sufficient to confer multiple antibiotic resistance in Escherichia coli. AB - A genetic approach was undertaken to identify normal bacterial genes whose products function to limit the effective concentration of antibiotics. In this approach, a multicopy plasmid library containing cloned Escherichia coli chromosomal sequences was screened for transformants that showed increased resistance to a number of unrelated antibiotics. Three such plasmids were identified, and all contained sequences originating from the mar locus. DNA sequence analysis of the minimal complementation unit revealed that the resistance phenotype was associated with the presence of the marA gene on the plasmids. The putative marA gene product is predicted to contain a helix-turn helix DNA binding domain that is very similar to analogous domains found in three other E. coli proteins. One such similarity was to the SoxS gene product, the elevated expression of which has previously been associated with the multiple antibiotic resistance (Mar) phenotype. Constitutive expression of marA conferred antibiotic resistance even in cells carrying a deletion of the chromosomal mar locus. We have also found that transformants bearing marA plasmids show a significant reduction in ompF translation but not transcription, similar to previously described mar mutants. However, this reduction in ompF expression plays only a minor role in the resistance mechanism, suggesting that functions encoded by genes unlinked to mar must be affected by marA. These results suggest that activation of marA is the ultimate event that occurs at the mar locus during the process that results in multiple antibiotic resistance. PMID- 8491711 TI - Molecular structures and functions of pyocins S1 and S2 in Pseudomonas aeruginosa. AB - Pyocins S1 and S2 are S-type bacteriocins of Pseudomonas aeruginosa with different receptor recognition specificities. The genetic determinants of these pyocins have been cloned from the chromosomes of P. aeruginosa NIH-H and PAO, respectively. Each determinant constitutes an operon encoding two proteins of molecular weights 65,600 and 10,000 (pyocin S1) or 74,000 and 10,000 (pyocin S2) with a characteristic sequence (P box), a possible regulatory element involved in the induction of pyocin production, in the 5' upstream region. These pyocins have almost identical primary sequences; only the amino-terminal portions of the large proteins are substantially different. The sequence homology suggests that pyocins S1 and S2, like pyocin AP41, originated from a common ancestor of the E2 group colicins. Purified pyocins S1 and S2 make up a complex of the two proteins. Both pyocins cause breakdown of chromosomal DNA as well as complete inhibition of lipid synthesis in sensitive cells. The large protein, but not the pyocin complex, shows in vitro DNase activity. This activity is inhibited by the small protein of either pyocin. Putative domain structures of these pyocins and their killing mechanism are discussed. PMID- 8491712 TI - Cloning, nucleotide sequence, and regulation of the Bacillus subtilis pbpE operon, which codes for penicillin-binding protein 4* and an apparent amino acid racemase. AB - Penicillin-binding protein 4* (PBP 4*) was purified from Bacillus subtilis, its N terminal sequence was determined, and the coding gene, termed pbpE, was cloned and sequenced. The predicted amino acid sequence of PBP 4* exhibited similarity to those of other penicillin-recognizing enzymes. Downstream of pbpE there was a second gene, termed orf2, which exhibited sequence similarity with aspartate racemase. The two genes were found to constitute an operon adjacent to and divergently transcribed from the sacB gene at 296 degrees on the chromosomal map. A weak beta-lactamase activity was associated with PBP 4*, but no enzymatic activity was found for the product of orf2. Mutation of pbpE, orf2, or both genes resulted in no observable effect on growth, sporulation, spore heat resistance, or spore germination. A translational pbpE-lacZ fusion was weakly expressed during vegetative growth and was significantly induced at the onset of sporulation. This induction depended on the activity of the spo0A product in relieving repression by the abrB repressor. A single transcription start site which was apparently dependent on E sigma A was detected upstream of pbpE. PMID- 8491713 TI - Expression of the nifBfdxNnifOQ region of Azotobacter vinelandii and its role in nitrogenase activity. AB - The nifBQ transcriptional unit of Azotobacter vinelandii has been previously shown to be required for activity of the three nitrogenase systems, Mo nitrogenase, V nitrogenase, and Fe nitrogenase, present in this organism. We studied regulation of expression and the role of the nifBQ region by means of translational beta-galactosidase fusions to each of the five open reading frames: nifB, orf2 (fdxN), orf3 (nifO), nifQ, and orf5. Expression of the first three open reading frames was observed under all three diazotrophic conditions; expression of orf5 was never observed. Genes nifB and fdxN were expressed at similar levels. With Mo, expression of nifO and nifQ was approximately 20- and approximately 400-fold lower than that of fdxN, respectively. Without Mo, expression of nifB dropped three- to fourfold and that of nifQ dropped to the detection limit. However, expression of nifO increased threefold. The products of nifB, fdxN, nifO, and nifQ have been visualized in A. vinelandii as beta galactosidase fusion proteins with the expected molecular masses. The NifB- fusion lacked activity for any of the three nitrogenase systems and showed an iron-molybdenum cofactor-deficient phenotype in the presence of Mo. The FdxN- mutation resulted in reduced nitrogenase activities, especially when V was present. Dinitrogenase activity in extracts was similarly affected, suggesting a role of FdxN in iron-molybdenum cofactor synthesis. The NifO(-)-producing mutation did not affect any of the nitrogenases under standard diazotrophic conditions. The NifQ(-)-producing mutation resulted in an increased (approximately 1,000-fold) Mo requirement for Mo nitrogenase activity, a phenotype already observed with Klebsiella pneumoniae. No effect of the NifQ(-) producing mutation on V or Fe nitrogenase was found; this is consistent with its very low expression under those conditions. Mutations in orf5 had no effect on nitrogenase activity. PMID- 8491714 TI - Identification of an early-stage gene of Chlamydia psittaci 6BC. AB - Chlamydiae are parasitic bacteria characterized by a temporally regulated developmental cycle. In the early stage of the cycle, metabolically inert elementary bodies reorganize to dividing reticulate bodies, a process about which little is known. The purpose of this investigation was to identify and clone chlamydial genes that are expressed preferentially during the early stage of the developmental cycle of Chlamydia psittaci 6BC. Several potential early genes were cloned with highly radioactive, host-free-generated RNA probes to screen a genomic library. One clone appeared to encode a gene that was particularly well expressed at 1 h postinfection. In further characterization, we found that it encodes two complete open reading frames and one partial open reading frame of 370 codons. The partial open reading frame, designated gltX, is very similar to bacterial glutamyl-tRNA synthetases and was demonstrated to be transcribed in vivo at 24 h postinfection by primer extension analysis. A lysine-rich open reading frame (LRO) of 117 codons was found upstream and divergent from gltX. The LRO lacks homology to known proteins, and we were unable to demonstrate that it is transcribed in vivo. The third open reading frame, of 182 codons, was found to be convergent with and partially overlap the LRO. It was confirmed to be preferentially expressed within the first 1.5 h of infection by Northern (RNA) blot analysis and was designated the early upstream open reading frame (EUO). Like the LRO, the EUO is not homologous to known proteins. A major potential transcription start site of the EUO was identified by primer extension analysis. However, the sequence upstream of the site does not closely resemble the consensus recognition sequences of bacterial sigma factors even though it is AT rich. The EUO is the first chlamydial gene specific to the early stage to be cloned and sequenced. PMID- 8491715 TI - A bifunctional enzyme, with separate xylanase and beta(1,3-1,4)-glucanase domains, encoded by the xynD gene of Ruminococcus flavefaciens. AB - Adjacent regions of a Ruminococcus flavefaciens 17 DNA fragment were found to encode xylanase and beta(1,3-1,4)-glucanase activities. Sequencing of this fragment showed that both activities are encoded by a single 2,406-bp open reading frame corresponding to the xynD gene. The predicted product has a characteristic signal sequence that is followed by an amino-terminal domain related to family G xylanases, while the carboxyterminal domain is related to beta(1,3-1,4)-glucanases from several other bacterial species. These two domains are connected by a region of unknown function that consists of 309 amino acids and includes a 30-amino-acid threonine-rich sequence. A polypeptide having a molecular weight of approximately 90,000 and exhibiting xylanase and beta(1,3 1,4)-glucanase activities was detected in Escherichia coli cells carrying the cloned xynD gene. This is one of the first cases in which a microbial polysaccharidase has been shown to carry separate catalytic domains active against different plant cell wall polysaccharides within the same polypeptide. xynD is one of a family of related genes in R. flavefaciens that encode enzymes having multiple catalytic domains, and the amino terminus of XYLD exhibits a high degree of similarity with the corresponding regions of another xylanase, XYLA, which carries two different xylanase catalytic domains. PMID- 8491716 TI - Full expression of the cryIIIA toxin gene of Bacillus thuringiensis requires a distant upstream DNA sequence affecting transcription. AB - The cryIIIA gene encoding a coleopteran-specific toxin is poorly expressed in Bacillus thuringiensis when cloned in a low-copy-number plasmid. This weak expression is observed when the gene is cloned only with its promoter and its putative terminator. cryIIIA gene expression was analyzed by using deletion derivatives of a larger DNA fragment carrying the toxin gene and additional adjacent sequences. The results indicate that a 1-kb DNA fragment located 400 bp upstream of the promoter strongly enhances CryIIIA production in B. thuringiensis sporulating cells. Similar results were obtained when the low-copy-number plasmid pHT304 carrying transcriptional fusions between upstream regions of cryIIIA and the lacZ gene was used. Analysis of the start sites, the sizes, and the amounts of cryIIIA-specific mRNAs shows that the enhancement occurs at the transcriptional level by increasing the number of cryIIIA-specific transcripts from the onset of sporulation to about 6 h after the onset of sporulation. The nucleotide sequence of the 1-kb activating fragment and of the 700 bp containing the promoter region and the 5' end of cryIIIA were determined. No potential protein-coding sequences were found upstream of the promoter. The major characteristic of the 1-kb activating fragment is the presence of a 220-bp A + T rich region. PMID- 8491717 TI - Purification and characterization of NADH oxidase from Serpulina (Treponema) hyodysenteriae. AB - NADH oxidase (EC 1.6.99.3) was purified from cell lysates of Serpulina (Treponema) hyodysenteriae B204 by differential ultracentrifugation, ammonium sulfate precipitation, and chromatography on anion-exchange, dye-ligand-affinity, and size-exclusion columns. Purified NADH oxidase had a specific activity 119 fold higher than that of cell lysates and migrated as a single band during denaturing gel electrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]). The enzyme was a monomeric protein with an estimated molecular mass of 47 to 48 kDa, as determined by SDS-PAGE and size-exclusion chromatography. Optimum enzyme activity occurred in buffers with a pH between 5.5 and 7.0. In the presence of oxygen, beta-NADH but not alpha-NADH, alpha-NADPH, or beta-NADPH was rapidly oxidized by the enzyme (Km = 10 microM beta-NADH; Vmax = 110 mumol beta-NADH min-1 mg of protein-1). Oxygen was the only identified electron acceptor for the enzyme. On isoelectric focusing gels, the enzyme separated into three subforms, with isoelectric pH values of 5.25, 5.35, and 5.45. Purified NADH oxidase had a typical flavoprotein absorption spectrum, with peak absorbances at wavelengths of 274, 376, and 448 nm. Flavin adenine dinucleotide was identified as a cofactor and was noncovalently associated with the enzyme at a molar ratio of 1:1. Assays of the enzyme after various chemical treatments indicated that a flavin cofactor and a sulfhydryl group(s), but not a metal cofactor, were essential for activity. Hydrogen peroxide and superoxide were not yielded in significant amounts by the S. hyodysenteriae NADH oxidase, indirect evidence that the enzyme produces water from reduction of oxygen with NADH. The N-terminal amino acid sequence of the NADH oxidase was determined to be MKVIVIGCHGAGTWAAK. In its biochemical properties, the NADH oxidase of S. hyodysenteriae resembles the NADH oxidase of another intestinal bacterium, Enterococcus faecalis. PMID- 8491718 TI - Comparison of lipids A of several Salmonella and Escherichia strains by 252Cf plasma desorption mass spectrometry. AB - Plasma desorption mass spectrometry has recently been used with success to characterize underivatized lipid A preparations: the major molecular species present give signals indicating their masses, from which probable compositions could be inferred by using the overall composition determined by chemical analyses. In the present study, plasma desorption mass spectrometry was used to compare structures in lipid A preparations isolated from several smooth and rough strains of Escherichia and Salmonella species. Preparations isolated from strains of both genera revealed considerable variation in degree of heterogeneity (number of fatty acids and presence or absence of hexadecanoic acid, phosphorylethanolamine, and aminoarabinose). Molecular species usually associated with Salmonella lipid A were found in preparations from Escherichia sp. In addition, preparations from three different batches of lipid A from one strain of Salmonella minnesota showed significant differences in composition. These results demonstrate that preparations used for biological and structural analyses should be defined in terms of their particular molecular constituents and that no generalizations based on analysis of a single preparation should be made. PMID- 8491719 TI - Characterization of the baiH gene encoding a bile acid-inducible NADH:flavin oxidoreductase from Eubacterium sp. strain VPI 12708. AB - A cholate-inducible, NADH-dependent flavin oxidoreductase from the intestinal bacterium Eubacterium sp. strain VPI 12708 was purified 372-fold to apparent electrophoretic homogeneity. The subunit and native molecular weights were estimated to be 72,000 and 210,000, respectively, suggesting a homotrimeric organization. Three peaks of NADH:flavin oxidoreductase activity (forms I, II, and III) eluted from a DEAE-high-performance liquid chromatography column. Absorption spectra revealed that purified form III, but not form I, contained bound flavin, which dissociated during purification to generate form I. Enzyme activity was inhibited by sulfhydryl-reactive compounds, acriflavine, o phenanthroline, and EDTA. Activity assays and Western blot (immunoblot) analysis confirmed that expression of the enzyme was cholate inducible. The first 25 N terminal amino acid residues of purified NADH:flavin oxidoreductase were determined, and a corresponding oligonucleotide probe was synthesized for use in cloning of the associated gene, baiH. Restriction mapping, sequence data, and RNA blot analysis suggested that the baiH gene was located on a previously described, cholate-inducible operon > or = 10 kb long. The baiH gene encoded a 72,006-Da polypeptide containing 661 amino acids. The deduced amino acid sequence of the baiH gene was homologous to that of NADH oxidase from Thermoanaerobium brockii, trimethylamine dehydrogenase from methylotrophic bacterium W3A1, Old Yellow Enzyme from Saccharomyces carlsbergensis, and the product of the baiC gene of Eubacterium sp. strain VPI 12708, located upstream from the baiH gene in the cholate-inducible operon. Alignment of these five sequences revealed potential ligands for an iron-sulfur cluster, a putative flavin adenine dinucleotide binding domain, and two other well-conserved domains of unknown function. PMID- 8491720 TI - Energetic efficiency of Escherichia coli: effects of mutations in components of the aerobic respiratory chain. AB - The aerobic respiratory chain of Escherichia coli can function with either of two different membrane-bound NADH dehydrogenases (NDH-1 and NDH-2) and with either of two ubiquinol oxidases (bd-type and bo-type). The amounts of each of these enzymes present in the E. coli membrane depend on growth conditions in general and particularly on the dissolved oxygen concentration. Previous in vitro studies have established that NDH-1 and NDH-2 differ in the extent to which they are coupled to the generation of an energy-conserving proton motive force. The same is true for the two ubiquinol oxidases. Hence, the bioenergetic efficiency of the aerobic respiratory chain must depend on the electron flux through each of the specific enzyme components which are being utilized. In this work, the specific rates of oxygen consumption for cells growing under glucose-limited conditions are reported for a series of isogenic strains in which one or more respiratory components are genetically eliminated. The results are compatible with the proton translocation values of the various components reported from in vitro measurements. The data show that (i) the bd-type oxidase is less efficient than is the bo-type oxidase, but the former is still a coupling site in the respiratory chain; and (ii) under the conditions employed, the wild-type strain uses both the NDH-1 and NDH-2 NADH dehydrogenases to a significant degree, but most of the electron flux is directed through the bo-type oxidase. PMID- 8491721 TI - Cloning, sequencing, and transcriptional analysis of the gene coding for the vegetative sigma factor of Agrobacterium tumefaciens. AB - The sigA gene of Agrobacterium tumefaciens was cloned and sequenced. Comparison with previously analyzed sigA genes revealed a high degree of similarity in nucleotide and amino acid sequences of regions two, three, and four of vegetative sigma factors. However, the upstream regulatory region shows no sequence homology with the Escherichia coli heat shock (sigma 32) promoters. It also does not contain the hairpin-loop structure (inverted repeat sequence) that was found in the upstream region of the groE operon in A. tumefaciens. The transcription initiation site of the gene was determined and found to be at the same position during normal growth and under heat shock conditions. Furthermore, no heat shock activation was observed at the transcriptional level. PMID- 8491722 TI - Characterization of Rhodobacter capsulatus genes encoding a molybdenum transport system and putative molybdenum-pterin-binding proteins. AB - The alternative, heterometal-free nitrogenase of Rhodobacter capsulatus is repressed by traces of molybdenum in the medium. Strains carrying mutations located downstream of nifB copy II were able to express the alternative nitrogenase even in the presence of high molybdate concentrations. DNA sequence analysis of a 5.5-kb fragment of this region revealed six open reading frames, designated modABCD, mopA, and mopB. The gene products of modB and modC are homologous to ChlJ and ChlD of Escherichia coli and represent an integral membrane protein and an ATP-binding protein typical of high-affinity transport systems, respectively. ModA and ModD exhibited no homology to known proteins, but a leader peptide characteristic of proteins cleaved during export to the periplasm is present in ModA, indicating that ModA might be a periplasmic molybdate-binding protein. The MopA and MopB proteins showed a high degree of amino acid sequence homology to each other. Both proteins contained a tandem repeat of a domain encompassing 70 amino acid residues, which had significant sequence similarity to low-molecular-weight molybdenum-pterin-binding proteins from Clostridium pasteurianum. Compared with that for the parental nifHDK deletion strain, the molybdenum concentrations necessary to repress the alternative nitrogenase were increased 4-fold in a modD mutant and 500-fold in modA, modB, and modC mutants. No significant inhibition of the heterometal-free nitrogenase by molybdate was observed for mopA mopB double mutants. The uptake of molybdenum by mod and mop mutants was estimated by measuring the activity of the conventional molybdenum-containing nitrogenase. Molybdenum transport was not affected in a mopA mopB double mutant, whereas strains carrying lesions in the binding-protein-dependent transport system were impaired in molybdenum uptake. PMID- 8491723 TI - Isolation of a cytochrome-deficient mutant strain of Sporomusa sphaeroides not capable of oxidizing methyl groups. AB - The homoacetogenic anaerobic bacterium Sporomusa sphaeroides was mutagenized with UV light. Taking advantage of the ampicillin enrichment technique and a newly developed test for the detection of heme in bacterial colonies, the cytochrome deficient mutant strain S. sphaeroides BK824 was isolated. In contrast to the wild type, this mutant strain failed to grow on betaine, betaine plus methanol, H2 plus CO2, and methanol plus CO2. Growth on betaine plus formate, betaine plus H2, betaine plus pyruvate, methanol plus H2 and CO2, and acetoin was not impaired. All enzymes of the Wood pathway as well as hydrogenase and carbon monoxide dehydrogenase were detectable at comparable activities in both the wild type and the cytochrome-deficient mutant. Labeling experiments with [14C]methanol demonstrated the inability of S. sphaeroides BK824 to oxidize methyl groups. The role of cytochromes in electron transport steps associated with the Wood pathway enzymes and their possible role in energy conservation during autotrophic growth in acetogens are discussed. PMID- 8491724 TI - Molecular characterization of a fructanase produced by Bacteroides fragilis BF-1. AB - The Bacteroides fragilis BF-1 fructanase-encoding gene (fruA) was cloned and expressed in Escherichia coli from the recombinant plasmid pBS100. The fruA gene consisted of 1,866 bp encoding a protein of 622 amino acids with a calculated M(r) of 70,286. The apparent M(r) of the fructanase, determined by in vitro cell free transcription-translation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, was approximately 71,500. An alignment of the amino acid sequences of the B. fragilis BF-1 fructanase and the Bacillus subtilis levanase revealed that 45.5% of the amino acids were identical. The fruA gene was expressed in E. coli from its own promoter; however, no E. coli promoter-like sequence was evident upstream from the gene. A major E. coli transcription start point and a single B. fragilis BF-1 transcription start point were located. Expression of the fruA gene was constitutive in E. coli(pBS100) and B. fragilis BF-1. The ratio of sucrase activity to inulinase activity (S/I ratio) was constant for enzyme preparations from E. coli (pBS100), indicating that both activities were associated with the fructanase. For B. fragilis BF-1, the S/I ratio varied considerably depending on the carbon source used for growth, suggesting that a separate sucrase is produced in addition to the fructanase in B. fragilis BF-1. Localization experiments and TnphoA mutagenesis indicated that the fructanase was exported to the periplasm. Sequence analysis of the N-terminal region of the fructanase revealed a putative 30-amino-acid signal peptide. The enzymatic properties of the purified fructanase were investigated. The enzyme was able to hydrolyze sucrose, raffinose, inulin, and levan but not melezitose, indicating that it was a beta-D-fructofuranosidase which was able to hydrolyze beta(2-->6)-linked fructans. PMID- 8491725 TI - The eubacterium Ectothiorhodospira halophila is negatively phototactic, with a wavelength dependence that fits the absorption spectrum of the photoactive yellow protein. AB - The motile, alkalophilic, and extremely halophilic purple sulfur bacterium Ectothiorhodospira halophila is positively photophobotactic. This response results in the accumulation of bacteria in light spots (E. Hustede, M. Liebergesell, and H. G. Schlegel, Photochem. Photobiol. 50:809-815, 1989; D. E. McRee, J. A. Tainer, T. E. Meyer, J. Van Beeumen, M. A. Cusanovich, and E. D. Getzoff, Proc. Natl. Acad. Sci. USA 86:6533-6537, 1989; also, this work). In this study, we demonstrated that E. halophila is also negatively phototactic. Video analysis of free-swimming bacteria and the formation of cell distribution patterns as a result of light-color boundaries in an anaerobic suspension of cells revealed the existence of a repellent response toward intense (but nondamaging) blue light. In the presence of saturating background photosynthetic light, an increase in the intensity of blue light induced directional switches, whereas a decrease in intense blue light gave rise to suppression of these reversals. To our knowledge, this is the first report of a true repellent response to light in a free-swimming eubacterium, since the blue light response in Escherichia coli and Salmonella typhimurium (B. L. Taylor and D. E. Koshland, Jr., J. Bacteriol. 123:557-569, 1975), which requires an extremely high light intensity, is unlikely to be a sensory process. The wavelength dependence of this negative photoresponse was determined with narrow band pass interference filters. It showed similarity to the absorption spectrum of the photoactive yellow protein from E. halophila. PMID- 8491727 TI - Immunochemistry and localization of the enzyme disaggregatase in Methanosarcina mazei. AB - The enzyme disaggregatase (Dag) from Methanosarcina mazei was studied immunochemically. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified Dag under reducing and nonreducing conditions revealed a single band with a 94-kDa molecular mass. Dag was found to be immunogenic in rabbits; a polyclonal antibody probe was prepared and used to detect the enzyme by slide immunoenzymatic assay, immunofluorescence, and immunoblotting in various species of Methanosarcina known to convert from packets to single cells, including M. mazei. The enzyme could not be detected in other members of the family Methanosarcinaceae that do not convert. By immunogold electron microscopy, Dag was mapped to the cell wall of packets and to the cell membrane of single cells of two M. mazei strains. PMID- 8491726 TI - An Aeromonas salmonicida gene which influences a-protein expression in Escherichia coli encodes a protein containing an ATP-binding cassette and maps beside the surface array protein gene. AB - A conserved Aeromonas salmonicida gene (abcA) affecting expression of the surface array protein gene (vapA) in Escherichia coli was identified. The 924-bp gene starts 205 bp after vapA and codes for a protein with a deduced molecular weight (M(r)) of 34,015 containing an N-terminal P-loop and significant homology to the ATP-binding cassette transport protein superfamily. AbcA was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) by using T7 polymerase expression and DNA-directed translation and was copurified with the sarkosyl-soluble cytoplasmic membrane fraction. The protein displayed aberrant migration during SDS-PAGE. A lacZ fusion containing 128 bp of upstream sequence and 387 bases in the 5' end of abcA was constructed, and the beta-galactosidase activity of the abcA-lacZ fusion gene was shown to be similar in E. coli and A. salmonicida. The 130,000-M(r) AbcA-LacZ fusion protein was purified, and by using an ATP affinity column, the 129 AbcA N-terminal P-loop-containing residues were shown to bind ATP. PMID- 8491728 TI - Synthesis of peptidoglycan and membrane during the division cycle of rod-shaped, gram-negative bacteria. AB - A modified procedure for determining the pattern of peptidoglycan synthesis during the division cycle has allowed the measurement of the rate of side wall synthesis during the division cycle without the contribution due to pole formation. As predicted by a model proposing that the surface growth of the cell is regulated by mass increase, we find a decrease in side wall synthesis in the latter half of the division cycle. This supports the proposal that, upon invagination, pole growth accommodates a significant proportion of the increasing cell mass and that residual side wall growth occurs in response to the residual mass increase not accommodated by pole volume. The observed side wall synthesis patterns support the proposal that mass increase is a major, and possibly sole, regulator of bacterial surface increase. Membrane synthesis during the division cycle of the gram-negative, rod-shaped bacteria Escherichia coli and Salmonella typhimurium has also been measured with similar methods. The rate of membrane synthesis--measured by incorporation of radioactive glycerol or palmitate relative to simultaneous labeling with radioactive leucine--exhibits the same pattern as peptidoglycan synthesis. The results are compatible with a model of cell surface growth containing the following elements. (i) During the period of the division cycle prior to invagination, growth of the cell occurs predominantly in the side wall and the cell grows only in length. (ii) When invagination begins, pole growth accommodates some cytoplasmic increase, leading to a concomitant decrease in side wall synthesis. (iii) Surface synthesis increases relative to mass synthesis during the last part of the division cycle because of pole formation. It is proposed here that membrane synthesis passively follows the pattern of peptidoglycan synthesis during the division cycle. PMID- 8491729 TI - Genetic and biochemical analysis of Salmonella typhimurium FliI, a flagellar protein related to the catalytic subunit of the F0F1 ATPase and to virulence proteins of mammalian and plant pathogens. AB - FliI is a Salmonella typhimurium protein that is needed for flagellar assembly and may be involved in a specialized protein export pathway that proceeds without signal peptide cleavage. FliI shows extensive sequence similarity to the catalytic beta subunit of the F0F1 ATPase (A. P. Volger, M. Homma, V. M. Irikura, and R. M. Macnab, J. Bacteriol. 173:3564-3572, 1991). It is even more similar to the Spa47 protein of Shigella flexneri (M. M. Venkatesan, J. M. Buysse, and E. V. Oaks, J. Bacteriol. 174:1990-2001, 1992) and the HrpB6 protein of Xanthomonas campestris (S. Fenselau, I. Balbo, and U. Bonas, Mol. Plant-Microbe Interact. 5:390-396, 1992), which are believed to play a role in the export of virulence proteins. Site-directed mutagenesis of residues in FliI that correspond to catalytically important residues in the F1 beta subunit resulted in loss of flagellation, supporting the hypothesis that FliI is an ATPase. FliI was overproduced and purified almost to homogeneity. It demonstrated ATP binding but not hydrolysis. An antibody raised against FliI permitted detection of the protein in wild-type cells and an estimate of about 1,500 subunits per cell. An antibody directed against the F1 beta subunit of Escherichia coli cross-reacted with FliI, confirming that the proteins are structurally related. The relationship between three proteins involved in flagellar assembly (FliI, FlhA, and FliP) and homologs in a variety of virulence systems is discussed. PMID- 8491730 TI - Suppression of replication-deficient mutants of IncFII plasmid NR1 can occur by two different mechanisms that increase expression of the repA1 gene. AB - Replication-proficient (Rep+) revertants were isolated from mutants of IncFII plasmid NR1 that were replication defective (Rep-). The parental Rep- plasmids contained a mutation that inactivated promoter PE for transcription of RNA-E, a trans-acting repressor of translation of the essential RepA1 replication initiation protein of NR1. The PE mutation also introduced a nonsense codon into a leader peptide gene that precedes and slightly overlaps the repA1 translation initiation site in the mRNA. This reduced the rate of synthesis of RepA1 by uncoupling its translation from that of the leader peptide. The reduced rate of RepA1 synthesis was responsible for the Rep- phenotype. All Rep+ revertants retained the PE mutation and contained second-site mutations responsible for suppression of the Rep- phenotype. One Rep+ revertant contained a second mutation adjacent to the Shine-Dalgarno sequence of repA1. Another Rep+ revertant contained a mutation in the repA2 gene, which encodes the trans-acting repressor of transcription of repA1. By using translational lacZ gene fusions, it was found that both kinds of suppressor mutation increased the expression of repA1 to a level sufficient to support replication. In both cases, the synthesis of RepA1 remained uncoupled from that of the leader peptide. The Shine-Dalgarno mutation increased the rate of leader peptide-independent translation of repA1 mRNA and also reduced the sensitivity of repA1 mRNA to inhibition by RNA-E. The repA2 mutation inactivated the RepA2 repressor and increased the rate of transcription of repA1 mRNA. The translational lacZ gene fusions were used to assess the range of regulation of expression of repA1 provided by each of the RNA-E and RepA2 regulatory circuits. By constructing miniplasmids that contained various combinations of the mutations, the contributions of the RNA-E and RepA2 regulatory circuits were assessed with respect to control of plasmid copy number and stable inheritance. Plasmids that lacked either circuit were less stable than wild-type plasmids. PMID- 8491731 TI - Volume growth of daughter and parent cells during the cell cycle of Saccharomyces cerevisiae a/alpha as determined by image cytometry. AB - The pattern of volume growth of Saccharomyces cerevisiae a/alpha was determined by image cytometry for daughter cells and consecutive cycles of parent cells. An image analysis program was specially developed to measure separately the volume of bud and mother cell parts and to quantify the number of bud scars on each parent cell. All volumetric data and cell attributes (budding state, number of scars) were stored in such a way that separate volume distributions of cells or cell parts with any combination of properties--for instance, buds present on mothers with two scars or cells without scars (i.e., daughter cells) and without buds--could be obtained. By a new method called intersection analysis, the average volumes of daughter and parent cells at birth and at division could be determined for a steady-state population. These volumes compared well with those directly measured from cells synchronized by centrifugal elutriation. During synchronous growth of daughter cells, the pattern of volume increase appeared to be largely exponential. However, after bud emergence, larger volumes than those predicted by a continuous exponential increase were obtained, which confirms the reported decrease in buoyant density. The cycle times calculated from the steady state population by applying the age distribution equation deviated from those directly obtained from the synchronized culture, probably because of inadequate scoring of bud scars. Therefore, for the construction of a volume-time diagram, we used volume measurements obtained from the steady-state population and cycle times obtained from the synchronized population. The diagram shows that after bud emergence, mother cell parts continue to grow at a smaller rate, increasing about 10% in volume during the budding period. Second-generation daughter cells, ie., cells born from parents left with two scars, were significantly smaller than first-generation daughter cells. Second- and third-generation parent cells showed a decreased volume growth rate and a shorter budding period than that of daughter cells. PMID- 8491732 TI - Mutational analysis of the regulatory region of the srfA operon in Bacillus subtilis. AB - Transcription of the Bacillus subtilis srfA operon is dependent on the transcriptional activator ComA. Mutational analysis of the srfA regulatory region suggests that two regions of dyad symmetry upstream of the srfA promoter may function in transcriptional activation by facilitating a cooperative interaction between ComA dimers. PMID- 8491733 TI - Yeast MAK3 N-acetyltransferase recognizes the N-terminal four amino acids of the major coat protein (gag) of the L-A double-stranded RNA virus. AB - The MAK3 gene of Saccharomyces cerevisiae encodes an N-acetyltransferase whose acetylation of the N terminus of the L-A double-stranded RNA virus major coat protein (gag) is necessary for viral assembly. We show that the first 4 amino acids of the L-A gag protein sequence, MLRF, are a portable signal for N-terminal acetylation by MAK3. Amino acids 2, 3, and 4 are each important for acetylation by the MAK3 enzyme. In yeast cells, only three mitochondrial proteins are known to have the MAK3 acetylation signal, suggesting an explanation for the slow growth of mak3 mutants on nonfermentable carbon sources. PMID- 8491734 TI - Component A2 of methylcoenzyme M reductase system from Methanobacterium thermoautotrophicum delta H: nucleotide sequence and functional expression by Escherichia coli. AB - The gene for component A2 of the methylcoenzyme M reductase system from Methanobacterium thermoautotrophicum delta H was cloned, and its nucleotide sequence was determined. The gene for A2, designated atwA, encodes an acidic protein of 59,335 Da. Amino acid sequence analysis revealed partial homology of A2 to a number of eucaryotic and bacterial proteins in the ATP-binding cassette (ABC) family of transport systems. Component A2 possesses two ATP-binding domains. A 2.2-kb XmaI-BamHI fragment containing atwA and the surrounding open reading frames was cloned into pGEM-7Zf(+). A cell extract from this strain replaced purified A2 from M. thermoautotrophicum delta H in an in vitro methylreductase assay. PMID- 8491735 TI - Frameshifting in the expression of the Escherichia coli trpR gene is modulated by translation initiation. AB - The Escherichia coli trpR gene encodes the 108-amino-acid-long Trp repressor. We have shown previously that a +1 frameshifting event occurs during the expression of trpR, resulting in the synthesis of an additional (+1 frame) polypeptide. Using trpR-lac'Z fusions, we have recently found that the transition from the 0 to the +1 frame occurs via the bypassing of a 55-nucleotide-long segment of the trpR+1-lac'Z mRNA (I. Benhar, and H. Engelberg-Kulka, Cell 72:121-130, 1993). Here we show that the frequency of trpR frameshifting (or bypassing) can be regulated both in vivo and in vitro. This frequency is inversely proportional to the rate of initiation of translation of the trpR gene. Hence, modulating the level of translation initiation affects the frequency of frameshifting. PMID- 8491736 TI - Isolation and characterization of a new chromosomal virulence gene of Agrobacterium tumefaciens. AB - A mutant (strain B119) of Agrobacterium tumefaciens with a chromosomal mutation was isolated by transposon (Tn5) mutagenesis. The mutant exhibited growth rates on L agar and minimal medium (AB) plates similar to those of the parent strain (strain A208 harboring a nopaline-type Ti plasmid). The mutant was avirulent on all host plants tested: Daucus carota, Cucumis sativus, and Kalanchoe diagremontiana. The mutant was not impaired in attachment ability to carrot cells. The mutant had one insertion of Tn5 in its chromosome. The avirulent phenotype of B119 was shown to be due to the Tn5 insertion in the chromosome by the marker exchange technique. A wild-type target chromosomal segment (3.0 kb) which included the site of mutation was cloned and sequenced. Two open reading frames, ORF-1 (468 bp) and ORF-2 (995 bp), were identified in the 3.0-kb DNA segment. Tn5 was inserted in the middle of ORF-2 (acvB gene). Introduction of the acvB gene into the mutant B119 strain complemented the avirulent phenotype of the strain. Homology search found no genes homologous to acvB, although it had some similarity to the open reading frame downstream of the virA gene on the Ti plasmid. Thus, the acvB gene identified in this study seems to be a new chromosomal virulence gene of A. tumefaciens. PMID- 8491737 TI - Characterization of intergenic spacers in two rrn operons of Enterococcus hirae ATCC 9790. AB - Two DNA restriction enzyme fragments coding for the 3' termini of 16S rRNA, the 5' termini of 23S rRNA, and the intergenic spaces between them in Enterococcus hirae ATCC 9790 were cloned and sequenced. The intergenic space of one of these genes contains a tRNA(Ala) sequence, whereas the other does not. Nevertheless, the intergenic spaces contain several regions that exhibit high levels of sequence homology and are capable of forming structures with similar base pairs. An analysis of Southern blots of chromosomal DNA cut with one and two restriction enzymes indicated that E. hirae has a total of six rrn operons. PMID- 8491738 TI - Specific in vitro guanylylation of a 43-kilodalton membrane-associated protein of Streptomyces coelicolor. AB - Incubation of [alpha-32P]GTP with cellular extracts or membranes of Streptomyces coelicolor labels a protein of 43 kDa, which was also labeled with [8,5'-3H]GTP but not with [alpha-32P]ATP or [gamma-32P]GTP. Radioactivity remained associated with this protein after boiling in 0.1 N NaOH, but it was dissociated after incubation in 0.1 N HCl or hydroxylamine. Chromatographic analysis of the HCl dissociated compound showed that GMP was the covalently bound nucleotide. Furthermore, guanylylation appeared to be reversible and to take place by a pyrophosphorylytic mechanism. Guanylylation was more efficient at low temperatures. Several Streptomyces species showed a guanylylated protein with a similar molecular mass. PMID- 8491739 TI - Characteristics of Mycoplasma hominis adhesion. AB - Mycoplasma hominis, a human pathogen, has previously been observed to bind to sulfatide separated on thin-layer chromatograms. It has not been demonstrated, however, that the binding is not simply a nonspecific ionic interaction. The ability of a low-passage patient isolate of M. hominis to adhere to glycoconjugates other than sulfatide and the characteristics of its binding to sulfatide were studied. Mycoplasmas were found to bind strongly and specifically in a temperature- and dose-dependent manner to only sulfatide of all of the glycolipids and glycoproteins tested. The avidity and specificity of binding, as well as the ability to inhibit the interaction specifically, suggest that the receptors to which M. hominis binds, particularly in the human urogenital tract, from which it is frequently isolated, are primarily, if not solely, sulfated glycolipids. PMID- 8491740 TI - Cloning and expression in Escherichia coli of the dnaK gene of Zymomonas mobilis. AB - The DnaK protein of Zymomonas mobilis (DnaKz) was identified and found to be 80% identical to the DnaK protein of Escherichia coli on the basis of the sequence of the N-terminal 21 amino acids. The dnaKz gene was cloned and found to be expressed in a thermosensitive dnaK mutant of Escherichia coli. Expression of the foreign gene restored a thermoresistant phenotype but failed to modulate the heat shock response in E. coli. PMID- 8491741 TI - Membrane permeabilization of Listeria monocytogenes and mitochondria by the bacteriocin mesentericin Y105. AB - Mesentericin Y105, a bacteriocin produced by a Leuconostoc mesenteroides strain, dissipates the plasma membrane potential of Listeria monocytogenes and inhibits the transport of leucine and glutamic acid. It also induces an efflux of preaccumulated amino acids from cells. In addition, the bacteriocin uncouples mitochondria by increasing state 4 respiration and decreasing state 3 respiration. The bacteriocin inhibits ATP synthase and adenine nucleotide translocase of the organelle while the affinity of ADP for its carrier is not modified. The results suggest that mesentericin Y105 acts by inducing, directly or indirectly, pore formation in the energy-transducing membranes, especially those of its natural target. PMID- 8491742 TI - Azospirillum brasilense locus coding for phosphoenolpyruvate:fructose phosphotransferase system and global regulation of carbohydrate metabolism. AB - Mutants of Azospirillum brasilense unable to grow on fructose include ones affected only on fructose (Fru-) and others impaired on many or all carbohydrates through interference with induction of their specific pathways (Car-). Both types of mutants could be complemented by a cosmid in broad-host-range vector pLAFR1 containing a 27.5-kb genomic insert, Car(-)-complementing activity depending on a 2.2-kb fragment, and Fru(-)-complementing activity depending on an overlapping 9.6-kb fragment. PMID- 8491743 TI - Before the American Burn Association. PMID- 8491744 TI - The first quinquennium: 1969 to 1973. PMID- 8491745 TI - The second quinquennium: 1974 to 1978. PMID- 8491746 TI - The third quinquennium: 1979 to 1983. PMID- 8491747 TI - The fourth quinquennium: 1984 to 1988. PMID- 8491748 TI - The fifth quinquennium: 1989 to 1993. PMID- 8491749 TI - Burn nursing history: the history of burn care. PMID- 8491750 TI - A silver anniversary tribute to therapists of the American Burn Association. AB - The year 1993 marks the Twenty-fifth Anniversary of the American Burn Association (ABA). Since Dr. Curtis P. Artz extended an invitation for membership in 1968, therapist membership has increased to 387 current members. During the quarter century the ABA has met, therapists have presented 211 abstracts, and 17 therapists have presented instructional courses and educational symposia. Thirty three therapists have moderated correlative sessions, and 95 therapists have fulfilled this capacity for Breakfast Symposia. The OT/PT Special Interest Group has been lead by 12 therapists, whereas 30 therapists have participated in two rehabilitation workshops. On the organizational level, three therapists have served as At-Large Members to the Board of Trustees, whereas 11 others have served on the At-Large Advisory Board. Sixty-three therapists have worked on 11 ABA committees. As senior authors, therapists have had 118 articles published in the Journal of Burn Care & Rehabilitation. In addition, four therapists have served the Journal in an editorial capacity. Therapists have been recognized for their efforts as recipients of Distinguished Service Awards, Educational Exchange Grants, and President's Continuing Education Awards. PMID- 8491751 TI - History of psychosocial care. PMID- 8491752 TI - The evolution of nutrition support in burns. PMID- 8491753 TI - Burn prevention: recollections. PMID- 8491754 TI - The development of burn centers in North America. AB - Burn center development in North America began in the mid 1940s, surged in the 1970s, and had reached virtually every distinct medical market by 1985. The authors present chronologies of the establishment of 137 currently active burn centers in the United States and 27 burn facilities in Canada, discuss public policy and other influences on burn center development, and review burn admissions trends. Another 46 U.S. hospitals are identified as having shown interest in caring for serious burn injuries in recent decades. Since national admissions data first became available in 1970, the proportion of U.S. patients with burns treated in burn centers has increased from 10% to 40%. Data were obtained from a survey of 197 hospitals in the United States and Canada listed in recent Burn Care Resources directories of the American Burn Association and annual surveys of the American Burn Association and the National Center for Health Statistics. Further study of burn centers in both institutional and societal contexts and submittal of archival material are encouraged. PMID- 8491755 TI - Journal of Burn Care & Rehabilitation. PMID- 8491756 TI - High malignant surface osteosarcoma arising at the site of a previously treated aneurysmal bone cyst. AB - A patient who developed a high malignant surface osteosarcoma at the site of a previously treated aneurysmal bone cyst is reported. The patient developed the osteosarcoma 4 years after complete curettage and bone-grafting of the cyst. The clinical, radiological and light microscopic features of this case are described. A causal relationship between the preexisting aneurysmal bone cyst and osteosarcoma is discussed, but seems to be unlikely. PMID- 8491757 TI - Phase 1 trials of intensive antineoplastic therapy: a need for a critical reassessment of who should be treated. PMID- 8491758 TI - Perspectives of surgery and multimodality treatment in gastric carcinoma. AB - Surgery still represents the therapy of choice for patients with primary gastric adenocarcinoma. The best survival results can be achieved if a potentially curative (R0) resection can be performed whatever the extent of resection of the primary tumor (total versus subtotal distal gastrectomy). Either procedure should be accompanied by systematic lymph node dissection since lymphadenectomy has relevant diagnostic (i.e. staging) and therapeutic implications (i.e. improved survival in stage II/IIIA disease). Since most gastric carcinomas are diagnosed in advanced tumor stages, the number of patients to be treated curatively by surgery alone remains limited. Multimodality treatment, consisting of chemotherapy and surgery, may be an encouraging alternative strategy. With actual chemotherapy protocols (i.e. 5-FU/doxorubicin/methotrexate, etoposide/doxorubicin/cisplatin) high remission rates in locally advanced irresectable lesions without distant metastases can be induced. Survival in these patients has been significantly improved after chemotherapy and second-look surgery. The effectiveness of these protocols in an adjuvant setting seems a worthwhile study for the future. In addition, immunological and somatic gene therapy may be of therapeutic impact in the next decade. PMID- 8491759 TI - Porokeratosis large skin lesions are susceptible to skin cancer development: histological and cytological explanation for the susceptibility. AB - Porokeratosis (PK), an autosomal dominant inherited skin disorder, is known to develop malignant skin tumors on its skin lesions. Our recent literature survey has revealed that large PK skin lesions are frequently a precursor of malignant changes. In the study, large and small PK skin lesions were investigated in terms of histological features of the epidermis and of the cellular DNA content of epidermal cells. Large PK lesions frequently showed hypertrophic epidermis with many mitotic cells, while small lesions usually presented atrophic epidermis without such mitotic cells. Abnormal cells, like those containing hyperchromatic, large, and/or irregularly shaped nuclei, were present in the epidermis of both large and small lesions with a preponderance in the former over the latter. DNA polyploidy was seen more frequently in large PK lesions than in small ones. DNA index values were significantly higher in large lesions than in small ones. The histological features and DNA ploidy abnormalities probably reflect the higher proliferation and the greater potential for malignant changes of large PK skin lesions. Our study helps to explain the clinical evidence that large PK skin lesions are frequently a precursor of malignant skin tumors. PMID- 8491760 TI - Expression of growth factors and their receptors in human esophageal carcinomas: regulation of expression by epidermal growth factor and transforming growth factor alpha. AB - The expression of mRNAs for epidermal growth factor (EGF), transforming growth factor alpha(TGF alpha), EGFR, platelet-derived growth factor (PDGF) A and B chain, PDGF receptor (PDGFR), transforming growth factor beta (TGF beta), erbB-2 and estrogen receptor (ER) genes was first examined in 6 human esophageal carcinoma cell lines, 6 xenoplanted and 15 surgically resected esophageal carcinomas. Secondly, the effect of EGF and TGF alpha on the expression of these genes by the TE-1 esophageal carcinoma cell line was investigated. The expression of EGF mRNA was detected in 8 (29.6%) of 27 tumors including the cell lines, whereas the TGF alpha and EGFR genes were expressed in 21 (77.8%) and 24 (88.9%) tumors respectively. PDGF B chain and PDGFR were detected in 18 (66.7%) and 20 (74.1%), respectively, and ER mRNA was observed in 16 (59.3%) tumors. Genes for PDGF A chain and TGF beta and the erbB-2 gene were commonly expressed. On the other hand, exogenous EGF and TGF alpha stimulated the expressions of fos and myc genes by TE-1 cells. The expression of mRNAs for TGF alpha, PDGF A and B chain and the erbB-2 genes was also increased after treatment with EGF. TGF alpha increased the accumulation of mRNAs for EGF, TGF alpha, EGFR, PDGF A and B chain and the erbB-2 gene. Moreover, the expression of mRNAs for interstitial collagenase, stromelysin and type IV collagenase was increased after EGF or TGF alpha treatment. These results indicate that EGF and TGF alpha may regulate the multi-growth-factor receptor expression and may play a central role for tumor invasion and metastasis as autocrine modulators for human esophageal carcinoma. PMID- 8491761 TI - Influence of syngeneic monoclonal anti-idiotypic antibodies to murine monoclonal antibodies against tumour-associated antigens on the biodistribution of their target antibodies and their fragments. AB - The effect of syngeneic anti-idiotypic (anti-id) antibodies on the biodistribution of three murine monoclonal antibodies (mAb) against human tumour associated antigens, and also on that of their fragments, has been examined in mice using, as a model system, purified anti-id mAb against three different target mAb. With the IgG2b mAb NCRC-2, pretreatment of mice 24 h previously with its IgG1 anti-id mAb NCRC-60 caused clearance of subsequently administered NCRC 2. With the univalent Fab/c fragment of NCRC-2 there was little effect, even with anti-id to Fab/c pretreatment ratios of 20:1, although immune complexes were present in the circulation. With Fab of NCRC-2, anti-id mAb prolonged blood survival by reducing renal clearance, immune complexes surviving in the circulation. With the IgG1 mAb NCRC-23, immune complexes formed in vivo with the IgG2b anti-id mAb NCRC-59, but with only little hepatic clearance. With the Fab and F(ab')2 fragments of NCRC-23, blood survival was increased in mice pretreated with anti-id mAb, and with Fab this was clearly due to reduced renal clearance. The third mAb, the IgG3 NCRC-48, formed complexes with its IgG2a anti-id mAb NCRC 62, but these survived in the circulation with no accelerated clearance of the target mAb. These results are different from those previously seen with endogenous anti-id responses. They indicate the diversity of effects that anti-id mAb can have on the biodistribution of their target mAb, and emphasise the difficulty of using such anti-id mAb to modulate the pharmacokinetics of target mAb. PMID- 8491762 TI - Immuno-biochemical assay for determination of nuclear steroid receptors during tamoxifen therapy. AB - The exact knowledge of hormone receptor status is critical for therapeutic strategies in hormone-dependent tumors. The influence of tamoxifen on estrogen receptor concentration has to be taken into account when evaluating results in tamoxifen-treated patients. We studied the receptor modulation of tumors xenotransplanted into nude mice (one breast and one endometrial carcinoma) after injection of 50 micrograms tamoxifen/mouse. To differentiate between unoccupied and occupied receptors, determinations were done by an enzyme immunoassay for the estrogen receptor under low- and high-salt extraction. With low-salt extraction we found a temporary decrease of the estrogen receptor concentration within the first hours after tamoxifen treatment. This decrease lasted for several days before recovery to pretreatment levels occurred. The hormone-receptor complexes, tightly bound to acceptor sites of the DNA, increased more than 15 times within 24 h. These values remained at increased levels for 2-7 days, after which a decrease to initial level was observed. PMID- 8491763 TI - Production of parathyroid hormone and parathyroid-hormone-related protein by breast cancer cells in culture. AB - Parathyroid-hormone-related protein (PTHrP) has been implicated in the origin of malignant hypercalcaemia. However, PTHrP production is not restricted to neoplastic cells, it is widespread among a variety of normal cell types and tissues. A physiological role for PTHrP has not been well defined. We describe a case of breast cancer with bone metastases and humoral hypercalcaemia of malignancy, with high levels of plasma C-terminal parathyroid hormone (PTH), mid molecule PTH and PTHrP. Cells from breast cancer biopsies were cultured and medium samples assayed for the C-terminal and mid-molecule fragments, intact PTH and PTHrP. The data indicate a progressive increase in both PTH fragments and PTHrP levels, over a period of 30 days. No temporal parallelism exists between PTH fragments and PTHrP concentrations, the former being maximum at the 14th day, and the latter at the 30th day from the beginning of the culture. Our results indicate a coproduction of PTH and PTHrP by the breast cancer cells both in vivo and in vitro. PMID- 8491764 TI - DNA ploidy, cell proliferation and steroid hormone receptors in endometrial hyperplasia and early adenocarcinoma. AB - We determined DNA content, S-phase fraction, and estrogen (ER) und progesterone receptor (PR) levels in 36 stage I endometrial adenocarcinomas and in 22 hyperplastic lesions to obtain information on the genesis and progression of endometrial malignancy. DNA aneuploidy was detected in 12/36 (33%) carcinomas and in none of the hyperplastic lesions. DNA aneuploidy was significantly more common in poorly and moderately differentiated carcinomas than in the well differentiated ones. Similarly, the highest number of cells in S-phase were found in poorly and moderately differentiated carcinomas, whereas well-differentiated carcinomas and all hyperplasias had an equally small S-phase fraction. Mean ER and PR levels were highest in hyperplastic lesions, especially those with atypical features, whereas carcinomas of all grades had significantly lower values. Thus, it is likely that the loss or decreased expression of steroid receptors is an early event during carcinogenesis in human endometrium, whereas an increase in the cell proliferation rate and the formation of DNA aneuploidy occur later during tumor progression. PMID- 8491765 TI - Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas. AB - The production of the cytokines interferon gamma (IFN gamma), interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significant lower levels of IFN gamma (P < or = 0.001), IL-2 (P < or = 0.01) and TNF alpha (P < or = 0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN gamma (P < or = 0.01), IL-2 (P < or = 0.001) and IL-1 alpha (P < or = 0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN-gamma levels, which was related to tumor burden. PMID- 8491766 TI - Genes, chromosomes and cancer. First meeting of the "Arbeitsgemeinschaft Molekular- und Zytogenetik (AEK)" of the Deutsche Krebsgesellschaft. PMID- 8491767 TI - Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. AB - The organization of eight small nuclear ribonucleoproteins (the U1, U2, U4, U5, and U6 RNAs previously studied by others and three additional snRNAs, U11, U12, and 7SK) has been investigated in cultured human cells by fluorescence in situ hybridization with antisense DNA and 2'-O-Me RNA oligonucleotides. Using highly sensitive digital imaging microscopy we demonstrate that all of these snRNAs are widespread throughout the nucleoplasm, but they are excluded from the nucleoli. In addition, the U2, U4, U5, U6, and U12 snRNAs are concentrated in discrete nuclear foci, known as coiled bodies, but U1 and 7SK are not. In addition to coiled bodies, a classic speckled pattern was observed in the nucleoplasm of monolayer-grown HeLa cells, whereas suspension-grown HeLa cells revealed a more diffuse nucleoplasmic labeling. Immunofluorescence staining using various snRNP specific antisera shows complete agreement with that of their antisense snRNA oligonucleotide counterparts. Although U2 RNA is concentrated in coiled bodies, quantitation of the fluorescence signals from the U2 antisense probe reveals that the bulk of the U2 snRNP is located in the nucleoplasm. Furthermore, simultaneous visualization of the U2 snRNAs and the tandemly repeated U2 genes demonstrates that coiled bodies are not the sites of U2 transcription. PMID- 8491768 TI - Evidence for channeled diffusion of pre-mRNAs during nuclear RNA transport in metazoans. AB - We report studies using an enhanced experimental system to investigate organization of nuclear pre-mRNA metabolism. It is based on the powerful genetic system and polytene nuclei of Drosophila. We observe (at steady state) movement of a specific pre-mRNA between its gene and the nuclear surface. This movement is isotropic, at rates consistent with diffusion and is restricted to a small nuclear subcompartment defined by exclusion from chromosome axes and the nucleolus. Bulk polyadenylated nuclear pre-mRNA precisely localizes in this same subcompartment indicating that most or all pre-mRNAs use the same route of intranuclear movement. In addition to association with nascent transcripts, snRNPs are coconcentrated with pre-mRNA in this subcompartment. In contrast to constitutive splices, at least one regulated splice occurs slowly and may undergo execution remotely from the site of pre-mRNA synthesis. Details of our results suggest that retention of incompletely spliced pre-mRNA is a function of the nuclear surface. We propose a simple model--based on channeled diffusion--for organization of intranuclear transport and metabolism of pre-mRNAs in polytene nuclei. We argue that this model can be generalized to all metazoan nuclei. PMID- 8491769 TI - Sec61p is adjacent to nascent type I and type II signal-anchor proteins during their membrane insertion. AB - We have identified membrane components which are adjacent to type I and type II signal-anchor proteins during their insertion into the membrane of the ER. Using two different cross-linking approaches a 37-38-kD nonglycosylated protein, previously identified as P37 (High, S., D. Gorlich, M. Wiedmann, T. A. Rapoport, and B. Dobberstein. 1991. J. Cell Biol. 113:35-44), was found adjacent to all the membrane inserted nascent chains used in this study. On the basis of immunoprecipitation, this ER protein was shown to be identical to the recently identified mammalian Sec61 protein. Thus, Sec61p is the principal cross-linking partner of both type I and type II signal-anchor proteins during their membrane insertion (this work), and of secretory proteins during their translocation (Gorlich, D., S. Prehn, E. Hartmann, K.-U. Kalies, and T. A. Rapoport. 1992. Cell. 71:489-503). We propose that membrane proteins of both orientations, and secretory proteins employ the same ER translocation sites, and that Sec61p is a core component of these sites. PMID- 8491770 TI - Two distinct populations of ARF bound to Golgi membranes. AB - ADP-ribosylation factor (ARF) is a small molecular weight GTP-binding protein (20 kD) and has been implicated in vesicular protein transport. The guanine nucleotide, bound to ARF protein is believed to modulate the activity of ARF but the mechanism of action remains elusive. We have previously reported that ARF binds to Golgi membranes after Brefeldin A-sensitive nucleotide exchange of ARF bound GDP for GTP gamma S. Here we report that treatment with phosphatidylcholine liposomes effectively removed 40-60% of ARF bound to Golgi membranes with nonhydrolyzable GTP, presumably by competing for binding of activated ARF to lipid bilayers. This revealed the presence of two different pools of ARF on Golgi membranes. Whereas total ARF binding did not appear to be saturable, the liposome resistant pool is saturable suggesting that this pool of ARF is stabilized by interaction with a Golgi membrane-component. We propose that activation of ARF by a guanine nucleotide-exchange protein results in association of myristoylated ARF GTP with the lipid bilayer of the Golgi apparatus. Once associated with the membrane, activated ARF can diffuse freely to associate stably with a target protein or possibly can be inactivated by a GTPase activating protein (GAP) activity. PMID- 8491771 TI - Oocyte maturation in starfish is mediated by the beta gamma-subunit complex of a G-protein. AB - The stimulation of meiotic maturation of starfish oocytes by the hormone 1 methyladenine is mimicked by injection of beta gamma subunits of G-proteins from either retina or brain. Conversely, the hormone response is inhibited by injection of the GDP-bound forms of alpha i1 or alpha t subunits, or by injection of phosducin; all of these proteins should bind free beta gamma. alpha-subunit forms with reduced affinity for beta gamma (alpha i1 or alpha t bound to hydrolysis-resistant GTP analogs, or alpha i1-GMPPCP treated with trypsin to remove the amino terminus of the protein) are less effective inhibitors of 1 methyladenine action. These results indicate that the beta gamma subunit of a G protein mediates 1-methyladenine stimulation of oocyte maturation. PMID- 8491772 TI - Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression. AB - Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of approximately 4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to < 1- < 0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to < 10, < 1, and increased approximately 250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype. PMID- 8491773 TI - Evidence for myoblast-extrinsic regulation of slow myosin heavy chain expression during muscle fiber formation in embryonic development. AB - Vertebrate muscles are composed of an array of diverse fast and slow fiber types with different contractile properties. Differences among fibers in fast and slow MyHC expression could be due to extrinsic factors that act on the differentiated myofibers. Alternatively, the mononucleate myoblasts that fuse to form multinucleated muscle fibers could differ intrinsically due to lineage. To distinguish between these possibilities, we determined whether the changes in proportion of slow fibers were attributable to inherent differences in myoblasts. The proportion of fibers expressing slow myosin heavy chain (MyHC) was found to change markedly with time during embryonic and fetal human limb development. During the first trimester, a maximum of 75% of fibers expressed slow MyHC. Thereafter, new fibers formed which did not express this MyHC, so that the proportion of fibers expressing slow MyHC dropped to approximately 3% of the total by midgestation. Several weeks later, a subset of the new fibers began to express slow MyHC and from week 30 of gestation through adulthood, approximately 50% of fibers were slow. However, each myoblast clone (n = 2,119) derived from muscle tissues at six stages of human development (weeks 7, 9, 16, and 22 of gestation, 2 mo after birth and adult) expressed slow MyHC upon differentiation. We conclude from these results that the control of slow MyHC expression in vivo during muscle fiber formation in embryonic development is largely extrinsic to the myoblast. By contrast, human myoblast clones from the same samples differed in their expression of embryonic and neonatal MyHCs, in agreement with studies in other species, and this difference was shown to be stably heritable. Even after 25 population doublings in tissue culture, embryonic stage myoblasts did not give rise to myoblasts capable of expressing MyHCs typical of neonatal stages, indicating that stage-specific differences are not under the control of a division dependent mechanism, or intrinsic "clock." Taken together, these results suggest that, unlike embryonic and neonatal MyHCs, the expression of slow MyHC in vivo at different developmental stages during gestation is not the result of commitment to a distinct myoblast lineage, but is largely determined by the environment. PMID- 8491774 TI - Differential regulation of tropomyosin isoform organization and gene expression in response to altered actin gene expression. AB - Phenotypically altered C2 myoblast cells, generated by the stable transfection of human nonmuscle actin genes (Schevzov, G., C. Lloyd, and P. Gunning. 1992. J. Cell Biol. 117:775-786), exhibit a differential pattern of tropomyosin cellular organization and isoform gene expression. The beta-actin transfectants displaying a threefold increase in the cell surface area, showed no significant changes in the pattern of organization of the high M(r) tropomyosin isoform, Tm 2, or the low M(r) tropomyosin isoform, Tm 5. In contrast, the gamma- and beta sm-actin gene transfectants, exhibiting a twofold decrease in the cell surface area, had an altered organization of Tm 2 but not Tm 5. In these actin transfectants, Tm 2 did not preferentially segregate into stress fiber-like structures and the intensity of staining was greatly diminished. Conversely, a well-defined stress fiber-like organization of Tm 5 was observed. The pattern of organization of these tropomyosin isoforms correlated with their expression such that a profound decrease in Tm 2 expression was observed both at the transcript and protein levels, whereas Tm 5 remained relatively unchanged. These results suggest that relative changes in nonmuscle actin gene expression can affect the organization and expression of tropomyosin in an isoform specific manner. Furthermore, this apparent direct link observed between actin and tropomyosin expression suggests that nonpharmacological signals originating in the cytoskeleton can regulate cytoarchitectural gene expression. PMID- 8491775 TI - Drosophila gamma-tubulin is part of a complex containing two previously identified centrosomal MAPs. AB - gamma-tubulin is a minor tubulin that is localized to the microtubule organizing center of many fungi and higher eucaryotic cells (Oakley, B. R., C. E. Oakley, Y. Yoon, and M. C. Jung. 1990. Cell. 61: 1289-1301; Stearns, T., L. Evans, and M. Kirschner. 1991. Cell. 65:825-836; Zheng, Y., M. K. Jung, and B. R. Oakley. 1991. Cell. 65:817-823). Here we show that gamma-tubulin is a component of a previously isolated complex of Drosophila proteins that contains at least two centrosomal microtubule-associated proteins called DMAP190 and DMAP60. Like DMAP190 and DMAP60, the gamma-tubulin in extracts of early Drosophila embryos binds to microtubules, although this binding may be indirect. Unlike DMAP190 and DMAP60, however, only 10-50% of the gamma-tubulin in the extract is able to bind to microtubules. We show that gamma-tubulin binds to a microtubule column as part of a complex, and a substantial fraction of this gamma-tubulin is tightly associated with DMAP60. As neither alpha- nor beta-tubulin bind to microtubule columns, the gamma-tubulin cannot be binding to such columns in the form of an alpha:gamma or beta:gamma heterodimer. These observations suggest that gamma-tubulin, DMAP60, and DMAP190 are components of a centrosomal complex that can interact with microtubules. PMID- 8491776 TI - SF-assemblin, the structural protein of the 2-nm filaments from striated microtubule associated fibers of algal flagellar roots, forms a segmented coiled coil. AB - The microtubule associated system I fibers of the basal apparatus of the flagellate green alga Spermatozopsis similis are noncontractile and display a 28 nm periodicity. Paracrystals with similar periodicities are formed in vitro by SF assemblin, which is the major protein component of system I fibers. We have determined the amino acid sequence of SF-assemblin and show that it contains two structural domains. The NH2-terminal 31 residues form a nonhelical domain rich in proline. The rod domain of 253 residues is alpha-helical and seems to form a segmented coiled coil with a 29-residue repeat pattern based on four heptads followed by a skip residue. The distinct cluster of acidic residues at the COOH terminal end of the motifs (periodicity about 4 nm) may be related to tubulin binding of SF-assemblin and/or its self assembly. A similar structure has been predicted from cDNA cloning of beta-giardin, a protein of the complex microtubular apparatus of the sucking disc in the protozoan flagellate Giardia lamblia. Although the rod domains of SF-assemblin and beta-giardin share only 20% sequence identity, they have exactly the same length and display 42% sequence similarity. These results predict that system I fibers and related microtubule associated structures arise from molecules able to form a special segmented coiled coil which can pack into 2-nm filaments. Such molecules seem subject to a strong evolutionary drift in sequence but not in sequence principles and length. This conservation of molecular architecture may have important implications for microtubule binding. PMID- 8491777 TI - Bovine filensin possesses primary and secondary structure similarity to intermediate filament proteins. AB - The cDNA coding for calf filensin, a membrane-associated protein of the lens fiber cells, has been cloned and sequenced. The predicted 755-amino acid-long open reading frame shows primary and secondary structure similarity to intermediate filament (IF) proteins. Filensin can be divided into an NH2-terminal domain (head) of 38 amino acids, a middle domain (rod) of 279 amino acids, and a COOH-terminal domain (tail) of 438 amino acids. The head domain contains a di arginine/aromatic amino acid motif which is also found in the head domains of various intermediate filament proteins and includes a potential protein kinase A phosphorylation site. By multiple alignment to all known IF protein sequences, the filensin rod, which is the shortest among IF proteins, can be subdivided into three subdomains (coils 1a, 1b, and 2). A 29 amino acid truncation in the coil 2 region accounts for the smaller size of this domain. The filensin tail contains 6 1/2 tandem repeats which match analogous motifs of mammalian neurofilament M and H proteins. We suggest that filensin is a novel IF protein which does not conform to any of the previously described classes. Purified filensin fails to form regular filaments in vitro (Merdes, A., M. Brunkener, H. Horstmann, and S. D. Georgatos. 1991. J. Cell Biol. 115:397-410), probably due to the missing segment in the coil 2 region. Participation of filensin in a filamentous network in vivo may be facilitated by an assembly partner. PMID- 8491778 TI - The organization of F-actin and microtubules in growth cones exposed to a brain derived collapsing factor. AB - In previous work we characterized a brain derived collapsing factor that induces the collapse of dorsal root ganglion growth cones in culture (Raper and Kapfhammer, 1990). To determine how the growth cone cytoskeleton is rearranged during collapse, we have compared the distributions of F-actin and microtubules in normal and partially collapsed growth cones. The relative concentration of F actin as compared to all proteins can be measured in growth cones by rationing the intensity of rhodamine-phalloidin staining of F-actin to the intensity of a general protein stain. The relative concentration of F-actin is decreased by about one half in growth cones exposed to collapsing factor for five minutes, a time at which they are just beginning to collapse. During this period the relative concentration of F-actin in the leading edges of growth cones decreases dramatically while the concentration of F-actin in the centers decreases little. These results suggest that collapse is associated with a net loss of F-actin at the leading edge. The distributions of microtubules in normal and collapsing factor treated growth cones were examined with antibodies to tyrosinated and detyrosinated isoforms of alpha-tubulin. The tyrosinated form is found in newly polymerized microtubules while the detyrosinated form is not. The relative proximal-distal distributions of these isoforms are not altered during collapse, suggesting that rates of microtubule polymerization and depolymerization are not greatly affected by the presence of collapsing factor. An analysis of the distributions of microtubules before and after collapse suggests that microtubules are rearranged, but their polymerization state is unaffected during collapse. These results are consistent with the hypothesis that the brain derived collapsing factor has little effect on microtubule polymerization or depolymerization. Instead it appears to induce a net loss of F-actin at the leading edge of the growth cone. PMID- 8491779 TI - Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth. AB - The growth of A-1 fibroblasts depends on exogenous amyloid beta/A4 protein precursor (APP), providing a simple bioassay to study the function of APP. Our preliminary study, testing the activity of a series of fragments derived from the secreted form of APP-695 (sAPP-695) on this bioassay, has shown that at least one of the active sites of sAPP-695 was localized within a 40-mer sequence (APP296 335, Kang sequence; Roch, J.-M., I. P. Shapiro, M. P. Sundsmo, D. A. C. Otero, L. M. Refolo, N. K. Robakis, and T. Saitoh. 1992. J. Biol. Chem. 267:2214-2221). In the present study, to further characterize the growth-promoting activity of sAPP 695 on fibroblasts, we applied a battery of synthetic peptides on this bioassay and found that: (a) the sequence of five amino acids, RERMS (APP328-332), was uniquely required for the growth-promoting activity of sAPP-695; (b) the activity was sequence-specific because the reverse-sequence peptide of the active domain had no activity; and (c) the four-amino-acid peptide RMSQ (APP330-333), which partially overlaps the COOH-terminal side of the active sequence RERMS, could antagonize the activity of sAPP-695. Furthermore, a recombinant protein which lacks this active domain (APP20-591 without 306-335) did not promote fibroblast cell growth, suggesting that this domain is the only site of sAPP-695 involved in the growth stimulation. The availability of these biologically active, short peptides and their antagonists should prove to be an essential step for the elucidation of APP involvement in regulation of cellular homeostasis. PMID- 8491780 TI - HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids. AB - Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher. PMID- 8491781 TI - Control of lens epithelial cell survival. AB - We have studied the survival requirements of developing lens epithelial cells to test the hypothesis that most cells are programmed to kill themselves unless they are continuously signaled by other cells not to do so. The lens cells survived for weeks in both explant cultures and high-density dissociated cell cultures in the absence of other cells or added serum or protein, suggesting that they do not require signals from other cell types to survive. When cultured at low density, however, they died by apoptosis, suggesting that they depend on other lens epithelial cells for their survival. Lens epithelial cells cultured at high density in agarose gels also survived for weeks, even though they were not in direct contact with one another, suggesting that they can promote one another's survival in the absence of cell-cell contact. Conditioned medium from high density cultures promoted the survival of cells cultured at low density, suggesting that lens epithelial cells support one another's survival by secreting survival factors. We show for the first time that normal cell death occurs within the anterior epithelium in the mature lens, but this death is strictly confined to the region of the anterior suture. PMID- 8491782 TI - Expression of chicken vinculin complements the adhesion-defective phenotype of a mutant mouse F9 embryonal carcinoma cell. AB - A mutant cell line, derived from the mouse embryonal carcinoma cell line F9, is defective in cell-cell adhesion (compaction) and in cell-substrate adhesion. We have previously shown that neither uvomorulin (E-cadherin) nor integrins are responsible for the mutant phenotype (Calogero, A., M. Samuels, T. Darland, S. A. Edwards, R. Kemler, and E. D. Adamson. 1991. Dev. Biol. 146:499-508). Several cytoskeleton proteins were assayed and only vinculin was found to be absent in mutant (5.51) cells. A chicken vinculin expression vector was transfected into the 5.51 cells together with a neomycin-resistance vector. Clones that were adherent to the substrate were selected in medium containing G418. Two clones, 5.51Vin3 and Vin4, were analyzed by Nomarski differential interference contrast and laser confocal microscopy as well as by biochemical and molecular biological techniques. Both clones adhered well to substrates and both exhibited F-actin stress fibers with vinculin localized at stress fiber tips in focal contacts. This was in marked contrast to 5.51 parental cells, which had no stress fibers and no vinculin. The mutant and complemented F9 cell lines will be useful models for examining the complex interactions between cytoskeletal and cell adhesion proteins. PMID- 8491783 TI - Recombinant entactin promotes mouse primary trophoblast cell adhesion and migration through the Arg-Gly-Asp (RGD) recognition sequence. AB - In vitro culture of mouse blastocysts during the period coinciding with implantation has revealed that primary trophoblast cells can adhere and migrate in serum-free medium when provided with certain extracellular matrix components, including fibronectin and laminin. Tightly associated with laminin is the glycoprotein, entactin, that may play an important role in basement membrane assembly and cell attachment. Mouse blastocysts were studied using this in vitro model to determine whether entactin was capable of mediating trophoblast invasive activity. Although entactin has never been shown to promote cell migration, we report here that recombinant entactin supported blastocyst outgrowth in a dose dependent manner, with a maximal effect at 20-50 micrograms/ml. The ability of trophoblast cells to adhere and migrate on entactin was specifically inhibited by anti-entactin antibody, but not by antibodies raised against laminin. The synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, that contains the Arg-Gly-Asp (RGD) integrin recognition site, reversibly inhibited entactin-mediated blastocyst outgrowth in a dose-dependent manner, but had no effect on laminin-mediated outgrowth. The synthetic peptide, Gly-Phe-Arg-Gly-Asp-Gly-Gln, that comprises the actual RGD-containing sequence within entactin, promoted trophoblast outgrowth when immobilized on the substratum. Furthermore, a mutated recombinant entactin, altered to contain a Glu in place of Asp at the RGD site, provided no trophoblast cell adhesive activity. We conclude that entactin promotes trophoblast outgrowth through a mechanism mediated by the RGD recognition site, and that it may play an important role during invasion of the endometrial basement membrane at implantation. PMID- 8491784 TI - Regulation of in vitro capillary tube formation by anti-integrin antibodies. AB - Human endothelial cells are induced to form an anastomosing network of capillary tubes on a gel of collagen I in the presence of PMA. We show here that the addition of mAbs, AK7, or RMAC11 directed to the alpha chain of the major collagen receptor on endothelial cells, the integrin alpha 2 beta 1, enhance the number, length, and width of capillary tubes formed by endothelial cells derived from umbilical vein or neonatal foreskins. The anti-alpha 2 beta 1 antibodies maintained the endothelial cells in a rounded morphology and inhibited both their attachment to and proliferation on collagen but not on fibronectin, laminin, or gelatin matrices. Furthermore, RMAC11 promoted tube formation in collagen gels of increased density which in the absence of RMAC11 did not allow tube formation. Neither RMAC11 or AK7 enhanced capillary formation in the absence of PMA. Lumen structure and size were also altered by antibody RMAC11. In the absence of antibody the majority of lumina were formed intracellularly from single cells, but in the presence of RMAC11, multiple cells were involved and the lumen size was correspondingly increased. Endothelial cells were also induced to undergo capillary formation in fibrin gels after PMA stimulation. The addition of anti alpha v beta 3 antibodies promoted tube formation in fibrin gels and inhibited EC adhesion to and proliferation on a fibrinogen matrix. The enhancement of capillary formation by the anti-integrin antibodies was matrix specific; that is, anti-alpha v beta 3 antibodies only enhanced tube formation on fibrin gels and not on collagen gels while anti-alpha v beta 1 antibodies only enhanced tubes on collagen and not on fibrin gels. Thus we postulate that changes in the adhesive nature of endothelial cells for their extracellular matrix can profoundly effect their function. Anti-integrin antibodies which inhibit cell-matrix interactions convert endothelial cells from a proliferative phenotype towards differentiation which results in enhanced capillary tube formation. PMID- 8491785 TI - Activated platelets form protected zones of adhesion on fibrinogen and fibronectin-coated surfaces. AB - Leukocytes form zones of close apposition when they adhere to ligand-coated surfaces. Because plasma proteins are excluded from these contact zones, we have termed them protected zones of adhesion. To determine whether platelets form similar protected zones of adhesion, gel-filtered platelets stimulated with thrombin or ADP were allowed to adhere to fibrinogen- or fibronectin-coated surfaces. The protein-coated surfaces with platelets attached were stained with either fluorochrome-conjugated goat anti-human fibrinogen or anti-human fibronectin antibodies, or with rhodamine-conjugated polyethylene glycol polymers. Fluorescence microscopy revealed that F(ab')2 anti-fibrinogen (100 kD) did not penetrate into the contact zones between stimulated platelets and the underlying fibrinogen-coated surface, while Fab antifibrinogen (50 kD) and 10 kD polyethylene glycol readily penetrated and stained the substrate beneath the platelets. Thrombin- or ADP-stimulated platelets also formed protected zones of adhesion on fibronectin-coated surfaces. F(ab')2 anti-fibronectin and 10 kD polyethylene glycol were excluded from these adhesion zones, indicating that they are much less permeable than those formed by platelets on fibrinogen-coated surfaces. The permeability properties of protected zones of adhesion formed by stimulated platelets on surfaces coated with both fibrinogen and fibronectin were similar to the zones of adhesion formed on fibronectin alone. mAb 7E3, directed against the alpha IIb beta 3 integrin blocked the formation of protected adhesion zones between thrombin-stimulated platelets and fibrinogen or fibronectin coated surfaces. mAb C13 is directed against the alpha 5 beta 1 integrin on platelets. Stimulated platelets treated with this mAb formed protected zones of adhesion on surfaces coated with fibronectin. These protected zones were impermeable to F(ab')2 antifibronectin but were permeable to 10 kD polyethylene glycol. These results show that activated platelets form protected zones of adhesion and that the size of molecules excluded from these zones depends upon the composition of the matrix proteins to which the platelets adhere. They also show that formation of protected zones of adhesion by platelets requires alpha IIb beta 3 integrins while the permeability properties of these zones of adhesion are regulated by both alpha IIb beta 3 and alpha 5 beta 1 integrins. PMID- 8491786 TI - Synergistic action of calcium-ionophores and hyperthermia is best interpreted as thermal enhancement of calcium toxicity. AB - It has been shown that no relation exists between [Ca2+]i and hyperthermic cell killing, although heat-induced increase of [Ca2+]i can be observed in some cell lines. When ionophores are used, dose-dependent rises in [Ca2+]i may be found. Beyond a certain threshold of ionophore-induced increases in [Ca2+]i, cells may be killed. Different threshold levels of [Ca2+]i exist in different cell lines. Hyperthermia can act synergistically with calcium ionophores to potentiate cell killing. Since there is no causal relation between [Ca2+]i and heat toxicity, this synergism can be explained as heat enhanced Ca2+ toxicity. In the current report, it is shown that both ionophore-induced Ca2+ toxicity (37 degrees C) and its potentiation by heat are dependent on extracellular calcium and related to sustained increases in [Ca2+]i. With ionomycin concentrations up to 15 microM, no increase in [Ca2+]i was seen in cells maintained in medium without Ca2+. Ionomycin effects on intracellular compartments were absent, and the drug seemed to act solely on the level of the plasmamembrane. Also, the synergism of heat and ionomycin appeared to act at the plasmamembrane, because depletion of extracellular calcium completely abolished this synergistic effect. The data presented are also discussed in the light of controversies existing in the literature for the role of calcium in hyperthermic cell killing. PMID- 8491787 TI - Deficiencies in collagen phagocytosis by human fibroblasts in vitro: a mechanism for fibrosis? AB - Degradation of collagen by fibroblast phagocytosis is an important pathway for physiological remodelling of soft connective tissues. Perturbations of this pathway may provide a mechanism for the development of fibrotic lesions. As collagen phagocytosis may be regulated by either a change of the proportions or the activity of phagocytic cells, we quantified phagocytosis with an in vitro model system. Collagen-coated fluorescent latex beads were incubated with human gingival fibroblasts and the fluorescence associated with internalized beads was measured by flow cytometry. Cells from normal tissues that had been incubated with beads for 3 hours contained a mean of 64% phagocytic cells; however, a small subpopulation (10% of phagocytic cells) contained more than threefold higher numbers of beads per cell than the mean. In contrast, cells from fibrotic lesions exhibited a large reduction of the proportions of phagocytic cells (mean = 13.8%) and there were no cells with high numbers of beads. On the basis of 3H-Tdr labeling, cells from fibrotic lesions that had internalized beads failed to proliferate, in contrast to phagocytic cells from normal tissues, which underwent repeated cell divisions. This result was not due to variations of cell cycle phase as there was no preferential internalization of beads during different phases of the cell cycle. The low phagocytic rate of cells from fibrotic lesions was also not due to asymmetric partitioning of phagosomes at mitosis as videocinemicrography of bead-labeled phagosomes in single, pre-mitotic cells demonstrated that > 90% of phagocytic cells equally partitioned beads to daughter cells. To investigate if inhibition of phagocytosis could be replicated in vitro, cells were incubated with the fibrosis-inducing drugs nifedipine or dilantin. These cultures exhibited marked (15-75%), dose-dependent reductions in the proportions of phagocytic cells, but there was no reduction in bead number per cell. Fibrotic lesions appear to contain fibroblasts with marked deficiencies in phagocytosis and the reduced phagocytic activity of these cells may contribute to unbalanced degradation and fibrosis. PMID- 8491788 TI - Growth regulation of primary rat tracheal epithelial cell cultures by endogenous transforming growth factor-beta s. AB - Primary rat tracheal epithelial (RTE) cell cultures have previously been shown to secrete transforming growth factor-beta (TGF beta) and to be growth inhibited by exogenous TGF beta. The purpose of the present studies was to determine whether the endogenous TGF beta(s) were regulating the growth of RTE cell cultures and, if so, which isoforms were involved. Neutralizing antibodies specific to TGF beta 1 and TGF beta 2 were added to cultures, and their effects on several growth parameters were measured. Addition of antibodies to early cultures (day 1), resulted in 1.8- and 3-fold increases in colony formation and cell number, respectively, above control IgG-treated cultures. Antibody dose-response experiments revealed that TGF beta 2 was the predominant isoform inhibiting early RTE cell growth. The antibody treatments resulted in similar stimulation of early growth at low and high seeding densities, suggesting that the endogenous TGF beta s were acting locally. Anti-TGF beta 1 treatment of cultures at various stages of growth resulted in 1.2-1.7-fold increases in DNA synthesis above controls, whereas anti-TGF beta 2 treatment resulted in increased DNA synthesis only in early and late cultures (1.7- and 2.5-fold, respectively), but not during midlogarithmic growth. Continuous treatment with a combination of both antibodies resulted in increased growth and decreased exfoliation in early cultures, but had no effect on the slow down of growth in late cultures. Thus endogenous TGF beta s inhibited primarily early growth and contributed to, but did not appear to be responsible for, plateau of growth in late stage cultures. Antibody treatment of secondary cultures resulted in 4-70-fold increases in colony formation, depending on the age of the primary cultures when replated, indicating that endogenous production of both TGF beta 1 and TGF beta 2 greatly inhibits the subculturability of primary RTE cells. Other experiments suggested that cholera toxin enhances RTE cell growth in part by counteracting the inhibitory effects of endogenous TGF beta s. PMID- 8491789 TI - Hydrogen peroxide-induced oxidative stress to the mammalian heart-muscle cell (cardiomyocyte): nonperoxidative purine and pyrimidine nucleotide depletion. AB - Hydrogen peroxide (H2O2) overload may contribute to cardiac ischemia-reperfusion injury. We report utilization of a previously described cardiomyocyte model (J. Cell. Physiol., 149:347, 1991) to assess the effect of H2O2-induced oxidative stress on heart-muscle purine and pyrimidine nucleotides and high-energy phosphates (ATP, phosphocreatine). Oxidative stress induced by bolus H2O2 elicited the loss of cardiomyocyte purine and pyrimidine nucleotides, leading to eventual de-energization upon total ATP and phosphocreatine depletion. The rate and extent of ATP and phosphocreatine loss were dependent on the degree of oxidative stress within the range of 50 microM to 1.0 mM H2O2. At the highest H2O2 concentration, 5 min was sufficient to elicit appreciable cardiomyocyte high energy phosphate loss, the extent of which could be limited by prompt elimination of H2O2 from the culture medium. Only H2O2 dismutation completely prevented ATP loss during H2O2-induced oxidative stress, whereas various free-radical scavengers and metal chelators afforded no significant ATP preservation. Exogenously-supplied catabolic substrates and glycolytic or tricarboxylic acid cycle intermediates did not ameliorate the observed ATP and phosphocreatine depletion, suggesting that cardiomyocyte de-energization during H2O2-induced oxidative stress reflected defects in substrate utilization/energy conservation. Compromise of cardiomyocyte nucleotide and phosphocreatine pools during H2O2 induced oxidative stress was completely dissociated from membrane peroxidative damage and maintenance of cell integrity. Cardiomyocyte de-energization in response to H2O2 overload may constitute a distinct nonperoxidative mode of injury by which cardiomyocyte energy balance could be chronically compromised in the post-ischemic heart. PMID- 8491790 TI - CSF-1 stimulates nucleoside transport in S1 macrophages. AB - We have examined nucleoside transport (NT) in a cell line derived from primary day 7 murine bone marrow macrophages (S1 macrophages) in response to the macrophage growth factor, colony-stimulating factor 1 (CSF-1). Adenosine and uridine transport in quiescent S1 macrophages occurred primarily by two facilitated diffusional routes, one that was sensitive and one that was relatively resistant to the inhibitor nitrobenzylthioinosine (NBMPR). Addition of CSF-1 to quiescent cultures resulted in increased adenosine and uridine transport with biphasic kinetics with respect to the cell cycle. Basal NT activity was elevated (about twofold) within 15 min of CSF-1 addition, returned to near basal levels by 1 h, and then increased again (three- to fourfold) 8-12 h later, returning again to basal levels by 48 h post CSF-1 stimulation. We propose that the large increase in NT activity at 8-12 h corresponded with the time when cultures synchronously began to enter the S phase of the cell cycle. In addition to these changes in the absolute rates, the proportions of NBMPR-sensitive and NBMPR-insensitive transport also change after CSF-1 addition. Quiescent cultures exhibited primarily NBMPR-insensitive transport while logrithmically growing cultures exhibited primarily NBMPR-sensitive nucleoside transport activity. The increase in the NBMPR-sensitive component of the transport process paralleled a similar increase in the number of high-affinity NBMPR binding sites, suggesting that the mechanism for upregulating NBMPR-sensitive NT activity involves increases in the number of NBMPR-sensitive transporter sites. Interestingly, we were unable to detect Na(+)-dependent concentrative uptake of adenosine, uridine, or formycin-B either in the S1 macrophage cell line or in primary (day 7) murine macrophages. Thus these bone marrow derived macrophages did not display the characteristically large Na(+)-dependent transport systems observed by others in peritoneal macrophages, implying that these two populations of macrophages are, indeed, functionally distinct. PMID- 8491791 TI - Isoprenoid regulation of cell growth: identification of mevalonate-labelled compounds inducing DNA synthesis in human breast cancer cells depleted of serum and mevalonate. AB - Growth arrest induced by serum depletion and/or treatment with mevinolin (an inhibitor of mevalonate synthesis) in the human breast cancer cell line Hs578T was overcome by exogenous mevalonate, indicating that some product or metabolite of mevalonate may be involved in the mediation of serum-regulated growth of these cells. In the search for such compounds we first tested a variety of known end products of mevalonate with respect to their ability to counteract the inhibition of DNA synthesis caused by serum-free medium and mevinolin. Thereby high doses (10 micrograms/ml) of dolichol-20 were found to cause a partial counteraction. After straight-phase HPLC purification of endogenous lipids, isolated from 3H- or 14C-mevalonate-labelled Hs578T cultures, we found that non-sterol lipids co eluting with dolichols efficiently induced DNA synthesis. After further purification with reverse-phase HPLC it was confirmed that virtually all of this effect was achieved by compounds(s) (seen as a single UV and radioactive peak) co eluting with dolichol-20. Nanogram doses, at most, of this (these) compound(s) elicited a substantial stimulation of DNA synthesis. The lipid(s) also counteracted the inhibition by mevinolin of N-linked glycosylation, indicating that it (they) also interfere(s) with this processing. Since treatment with tunicamycin (an inhibitor of N-linked glycosylation) abolished this growth stimulative effect, N-linked glycosylation seems to be a necessary event in the processes leading to lipid-induced initiation of DNA synthesis. PMID- 8491792 TI - Different signal transduction by epidermal growth factor may be responsible for the difference in modulation of amino acid transport between fetal and adult hepatocytes. AB - [1-14C]-2-aminoisobutyric acid (AIB) uptake and signal transduction pattern after epidermal growth factor (EGF) stimulation were examined in freshly isolated hepatocytes from 20-day-old fetuses and 3-month-old rats. EGF induced a transient increase of AIB transport after 10 min only in adult animals; the observed unresponsiveness of fetal liver is not dependent on a lack of EGF receptors which are present though to a lesser extent on the plasma membrane in this period. As far as the production of the second messengers, inositol trisphosphate (IP3) and calcium, is concerned, substantial differences were found: EGF increased IP3 production in adult hepatocytes, whereas it had no effect in fetal ones. Moreover, the addition of EGF induced a calcium transient in hepatocytes from adult animals, while there was no increase in fetal cells. The lack of EGF effect on amino acid transport in fetal cells could be due to its inability to produce both IP3 and calcium transients, suggesting that this transduction pathway is not activated during fetal life. PMID- 8491793 TI - Isolation of a temperature-sensitive variant Chinese hamster ovary cell line with a morphologically altered endocytic recycling compartment. AB - We have enriched a mutagenized population of Chinese hamster ovary (CHO) cells for those defective in endocytosis by selection for survival to treatment with transferrin (Tf)-ricin and Tf-diphtheria toxin conjugates. Surviving cells were screened with a fluorescently labeled Tf uptake assay to identify cells with morphologically aberrant endocytic phenotypes. One of the cell lines identified, B104-5, has a striking temperature-induced alteration in the morphology of its endocytic receptor recycling compartment. In parental cells the tightly clustered endocytic recycling compartment is located near the Golgi complex. In the mutant cells, following incubation at 40 degrees C, this compartment appears fragmented and widely dispersed. Surprisingly, this alteration in the morphology of the recycling compartment has no effect on the kinetics of Tf internationalization and recycling. The wild-type endocytic compartment is closely aligned with the microtubule-organizing center and the Golgi apparatus, and like the Golgi, its clustered appearance is dependent upon intact microtubules. Although the disruption of the B104-5 receptor recycling compartment morphology can be phenocopied in wild-type cells by microtubule depolymerizing drugs, the microtubule cytoskeleton in B104-5 cells appears normal in immunofluorescent staining. B104-5 cells, unlike the parental cells, do not proliferate at 40 degrees C. The mutation in B104-5 cells is recessive, as fusion with wild-type cells results in a reversion of the B104-5 phenotype. The finding that the morphology of the recycling compartment in CHO cells can be altered without affecting recycling of endocytosed Tf is consistent with the variety of recycling compartment morphologies observed among different cell lines. An interpretation of this result is that the lesion in B104-5 cells is in a gene that is involved in determining the endocytic compartment morphologies observed in different cell lines. PMID- 8491794 TI - Myocyte DNA synthesis with aging: correlation with ventricular loading in rats. AB - To determine whether the detrimental mechanical and anatomical changes that occur biventricularly with aging are associated with activation of DNA synthesis, flow cytometric analysis was performed on myocyte nuclei prepared from the left and right ventricles of rats at 4, 12, 20, and 29 months of age. Heart weight increased significantly with age, and this growth adaptation was associated with the development of left ventricular failure and right ventricular dysfunction. These phenomena were coupled with marked elevations in diastolic wall stress and increases in the percentage of myocyte nuclei in S+G2M in both ventricles. Linear regression analyses revealed a direct correlation between the fraction of myocytes that entered the cell cycle and diastolic pressure and wall stress. An inverse relation was found between the percentage of myocyte nuclei in S+G2M and +dP/dt and systolic wall stress. Thus the depression of hemodynamic performance coupled with alterations in the loading conditions contributes, at least in part, to increased DNA synthesis in cardiac myocytes with age. PMID- 8491795 TI - Rudolph Matas: innovator of the operating room. PMID- 8491796 TI - No politics at NIH. PMID- 8491797 TI - Asymptomatic nonsustained ventricular arrhythmias. PMID- 8491798 TI - Mr. Arbuthnot returns to discuss health care. PMID- 8491799 TI - Chronic myelocytic leukemia. PMID- 8491800 TI - Whose standards? PMID- 8491801 TI - Management of the solitary pulmonary nodule. AB - Large lesions are often malignant and call for prompt resection. Small lesions are likely to be benign but nonetheless raise difficult questions. For example, how to estimate the potential for malignancy? Or, how to weigh the possible effectiveness of an aggressive surgical approach against possible complications? Probability techniques can provide support for clinical judgment. PMID- 8491802 TI - Hypothermia in the elderly. PMID- 8491803 TI - Issues in management of diabetic retinopathy. AB - Panretinal photocoagulation could prevent most blindness from proliferative disease--if risk is identified early. This makes it essential that primary physicians include annual ophthalmologic evaluation in the management of patients at risk. Meanwhile, studies are under way on promising medical approaches, including intensive insulin regimens, aldose reductase blockers, and angiogenesis inhibitors. PMID- 8491804 TI - Cancer invasion and metastasis. AB - Mechanisms by which primary tumors invade local tissues and spread to distant sites are beginning to be understood. Included are factors involved in cell-to cell and cell-to-extracellular matrix interactions, motility factors, and genetic controls. Knowledge of such mechanisms is spurring development of novel therapeutic agents for clinical study. PMID- 8491805 TI - Simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma by gas chromatography-mass spectrometry as indices of cholesterol and bile acid biosynthesis. AB - A very sensitive and specific method for the simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma is described. The assay is based on isotope dilution mass spectrometry: the extracts from plasma were treated with benzylamine followed by dimethylethylsilylimidazole, then the resulting dimethylethylsilyl ether derivatives of mevalonylbenzylamide and 7 alpha-hydroxycholesterol were determined by gas chromatography-mass spectrometry using high-resolution selected-ion monitoring. Simple regression analysis revealed significant correlations between the plasma level of mevalonate and the hepatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) (r = 0.83, P < 0.01) and between the plasma level of free 7 alpha hydroxycholesterol and the hepatic activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.7) (r = 0.76, P < 0.05). PMID- 8491806 TI - Assay of human plasma cortisone by liquid chromatography: normal plasma concentrations (between 8 and 10 a.m.) of cortisone and corticosterone. AB - A high-performance liquid chromatographic method using ultraviolet detection to quantitate human plasma concentrations of cortisone simultaneously with cortisol and corticosterone is described. The method is based on the use of an octadecyl silica column (100 mm x 2 mm I.D., 3 microns), an ultraviolet absorbance detector (242 nm) with a 10 mm path length flow-cell, and a mobile phase composed of water tetrahydrofuran-acetonitrile (82:10:8, v/v) containing 5 ml/l triethylamine and citric acid to adjust the pH of the buffer to 6.5. Flumethasone is used as the internal standard. The detection limit of the method for the three steroids is 300 ng/l using a 1-ml sample. The average inter-assay coefficient of variation for cortisone is 3.3% and the average recovery is 100.8%. Possible interferences from common drugs and endogenous and exogenous steroids in the method have been studied. Plasma concentrations (drawn from 8 to 10 a.m.) of cortisone and corticosterone for 43 normal volunteers have been determined. PMID- 8491807 TI - Quantification of carnitine and specific acylcarnitines by high-performance liquid chromatography: application to normal human urine and urine from patients with methylmalonic aciduria, isovaleric acidemia or medium-chain acyl-CoA dehydrogenase deficiency. AB - This paper describes the development of a high-performance liquid chromatographic method for the quantitation of free carnitine, total carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, hexanoylcarnitine and octanoylcarnitine in human urine. Carnitine and acylcarnitines were isolated from 10 or 25 microliters of urine using 0.5-ml columns of silica gel, derivatized with 4' bromophenacyl trifluoromethanesulfonate and separated by high-performance liquid chromatography. Using 4-(N,N-dimethyl-N-ethylammonio)-3-hydroxybutanoate ("e carnitine") as the internal standard, standard curves (10-300 nmol/ml) were generated. Carnitine and acylcarnitines were quantified (when they were present) in normal human urine and the urine of patients diagnosed with one of three different disorders of organic acid metabolism: methylmalonic aciduria, isovaleric aciduria, isovaleric acidemia, and medium-chain acyl-CoA dehydrogenase deficiency. PMID- 8491808 TI - Quantification of physiological amino acids by gradient ion-exchange high performance liquid chromatography. AB - A single-column gradient lithium ion-exchange chromatographic method with post column derivatization and fluorimetric detection for the quantification of physiological amino acids is described. The method runs automatically, requires a minimum of sample preparation, separates all amino acids in plasma and cerebrospinal fluid, and most compounds in brain extract, in addition to some amino acids used therapeutically and in pharmacological studies. About 40 compounds can be quantitated within a run time of 3 h. The within-assay and between-assay coefficients of variations for principal amino acids in plasma samples are satisfactory. The system has performed conveniently and with high stability in the daily routine work and is cost-saving based on laboratory prepared buffers. PMID- 8491809 TI - Separation of high-density lipoproteins into apolipoprotein E-poor and apolipoprotein E-rich subfractions by fast protein liquid chromatography using a heparin affinity column. AB - The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions. PMID- 8491810 TI - Purification of hyperexpressed Bacillus subtilis tRNA(Trp) cloned in Escherichia coli. AB - To study the effects of evolutionary sequence changes on the molecular interactions of tRNA inside the cell, the Bacillus subtilis tRNA(Trp) gene has been cloned into Escherichia coli JM109 under the control of the lac promotor. Hyperexpression of the gene in minimal medium upon induction yielded 28% of total tRNA in the form of B. subtilis tRNA(Trp). The tRNA(Trp) gene product was purified by the use of a single Vydac C4 high-performance liquid chromatography (HPLC) matrix. This experimental system provided a valuable system for the hyperexpression and purification of a heterologous tRNA for studies in vitro. Moreover, because HPLC fractionation of the heterologous tRNA(Trp) gene product yielded multiple peaks, the system made possible an analysis of the molecular mechanisms for the transcriptional modifications of the tRNA(Trp) gene product in vivo. PMID- 8491811 TI - Simple chromatographic systems permitting both DNA purification and separation of 2'-deoxyribonucleoside 3'-monophosphates as substrates for 32P-postlabelling studies. AB - The 32P-postlabelling method has recently been applied to the measurement of oxidative DNA damage. The assay requires the isolation of 2'-deoxyribonucleoside 3'-monophosphates subsequent to the extraction of DNA followed by its enzymatic digestion. As an alternative to the use of toxic and oxidizing solvents such as phenol, a simple purification method is proposed, based mainly on size-exclusion chromatography carried out either with ready-made columns (NAP-10, SEC-2000) or, more conveniently, with stainless-steel laboratory-packed columns (Fractogel HW 65 F). This method was applied to the purification of the DNA extracted from seeds of Lactuca sativa. After enzymatic digestion of DNA, the 2' deoxyribonucleoside 3'-monophosphates may be further separated in less than 30 min by high-performance liquid chromatography on a Hypersil octadecylsilylsilica gel column in the ion-suppression mode by using either ammonium formate (0.05 M, pH 6.5) or sodium succinate (0.02 M, pH 6.0). The use of these eluent systems is compatible with straightforward 32P-labelling of the 2'-deoxyribonucleoside 3' monophosphates without any concentration and desalting steps. PMID- 8491812 TI - Determination of tetrahydropapaveroline in the urine of parkinsonian patients receiving L-dopa-carbidopa (Sinemet) therapy by high-performance liquid chromatography. AB - Tetrahydropapaveroline (THP) concentrations were measured in the urine of Parkinsonian patients receiving L-dopa-carbidopa (Sinemet) therapy, using a method that employs a separation scheme that selectively isolates THP from urine and utilizes the Pictet-Spengler condensation of THP with formaldehyde combined with high-performance liquid chromatography for identification and determination. The mean (+/- S.D.) recoveries of THP from normal urine with 0.2 pmol/ml added and from Parkinsonian patients' urines with 0.5 pmol/ml added were 48.6 +/- 5.7 and 44.6 +/- 3.1%, respectively. Three Parkinsonian patients who were receiving either 250, 750 or 1000 mg of L-dopa (as Sinemet) daily had 24-h urinary THP excretion levels of 989, 1017 and 1600 pmol, respectively. PMID- 8491813 TI - High-performance liquid chromatographic determination of plasma ascorbic acid in relationship to health care. AB - We have developed a simple reversed-phase high-performance liquid chromatographic method for determining plasma ascorbic acid level and studied the relationship between its plasma concentration and fruit and vegetable intake and plasma dopamine-beta-hydroxylase activity. The samples were pretreated by precipitating the proteins and injected onto the column. Elution with a methanol gradient in sodium phosphate buffer was carried out by monitoring the absorbance at 265 nm, and the peak corresponding to ascorbic acid was well separated from other peaks of reagents used for pretreatment and from plasma endogenous components. The proposed method correlated well with the conventional dichlorophenol-indophenol method. Mean levels of ascorbic acid in normal human plasma were 0.86 +/- 0.36 mg/dl for males (twenty subjects, 19-28 years old) and 1.01 +/- 0.30 mg/dl for females (twenty subjects, 19-21 years old). There was good correlation between plasma ascorbic acid levels and dopamine-beta-hydroxylase levels, reflecting activities of daily living, but no correlation was found between these levels and dietary consumption of vegetables or fruits. PMID- 8491815 TI - Semi-automated solid-phase extraction procedure for drug screening in biological fluids using the ASPEC system in combination with Clean Screen DAU columns. AB - The use of a semi-automated solid-phase extraction system (ASPEC) for the screening of drugs in plasma and urine on a single mixed-mode column (Clean Screen DAU) is described. The processes of column preconditioning, sample application, column wash, pH adjustment and elution of the drugs were accomplished by the ASPEC. After off-line evaporation, the residues were injected into a wide-bore capillary gas chromatograph. The recoveries of the tested drugs were in the range of 73-96%, with relative standard deviations less than 5% at a concentration level of 2 micrograms/ml. PMID- 8491814 TI - Enhanced sensitivity of immunoblotting with peroxidase-conjugated antibodies using an adsorbed substrate method. AB - Immunoblots probed with immunoglobulin E (IgE)-containing sera from allergic patients are frequently used in allergy research. Current techniques for detection of specific IgE include radiolabeled and enzyme-linked methods. Although radiolabeled methods are very sensitive, many research groups prefer non radioactive procedures with equal or greater sensitivity. Alkaline phosphatase (AP) and horse radish peroxidase (HRP) are the most frequently used conjugating enzymes for immunoblotting with the former generally recognized as more sensitive. We describe a method of immunoblot detection using HRP-conjugated immunochemicals with sensitivity equal to and for some systems greater than that of AP conjugates. An adsorbed substrate method for developing immunoblots probed with HRP immunochemical conjugates is compared with traditional AP and HRP methods. The adsorbed substrate system, when used to detect IgE binding to allergic proteins, gives high resolution and delineates bands not otherwise seen. The system has advantages of high sensitivity, rapid development and conservation of immunochemicals. Problems of fading, sensitivity to heat and light, and high background can be solved with increased washing, prompt photography and computer scanning. PMID- 8491816 TI - Determination of ochratoxin A in urine and faeces of swine by high-performance liquid chromatography. AB - Sensitive methods for the determination of ochratoxin A in urine and faeces of swine are described. The samples were extracted with chloroform at pH < 2, and the extracts were cleaned up by a combination of solid-phase extraction and liquid-liquid partition. High-performance liquid chromatography with fluorescence detection was used for detection and determination. The detection limits were 0.3 ng/ml for urine and 1.5 ng/g for faeces. Recoveries of ochratoxin A from spiked samples of urine and faeces were 93% and 60%, respectively. Because of the low detection limit and the fast and relatively easy performance, the method for the determination of ochratoxin A in urine proved suitable for the estimation of possible contamination of live animals. PMID- 8491817 TI - Simultaneous determination of chloroquine and quinine in human biological fluids by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method with fluorescence detection is described for the simultaneous measurement of quinine, chloroquine and mono- and bidesethylchloroquine in human plasma, erythrocytes and urine. After a liquid solid extraction on a Bond Elut C8 cartridge, the compounds are separated on an Inertsil silica column by gradient elution; the mobile phase is a mixture of acetonitrile and methanol-25% ammonia solution (92.7:7.5, v/v). The eluent was monitored with a fluorescence detector (excitation wavelength 325 nm and emission wavelength 375 nm). The limit of detection was ca. 5 ng/ml for chloroquine and ca. 23 ng/ml for quinine. No chromatographic interferences could be detected from endogenous compounds or other antimalarial drugs. The method is accurate with inter- and intra-assay coefficients of variation lower than 7%. Hydroxychloroquine is used as an internal standard because of its structural similarity to chloroquine. The procedure requires 30 min and can be used for therapeutic drug monitoring. PMID- 8491818 TI - Determination of methotrexate in human urine at nanomolar levels by high performance liquid chromatography with column switching. AB - An high-performance liquid chromatographic method with column switching for the detection of less than 4 ng of methotrexate in the urine of oncologic nurses is described. Urine samples were purified by solid-phase extraction on silica-bonded phenyl columns, eluting impurities with ethyl acetate. After elution from the column, the analyte was concentrated ten-fold, evaporating the solvent. On a strong anion-exchange column (Nucleosil 100 SB), methotrexate was separated from the remaining interfering substances, was then switched to a reversed-phase column (LiChrospher 100 RP-18e), and finally eluted by a linear gradient in a solvent system consisting of ammonium formate buffer (pH 2.7) and acetonitrile. Absorbance was monitored at 310 nm. This method has proved to be suitable for detecting traces of methotrexate in urine in order to individualize risks and to reduce further the occupational safety hazard for hospital personnel. PMID- 8491819 TI - Quantitation of human plasma levels of the anticancer agent carboxyamidotriazole by high-performance liquid chromatography. AB - The predominant cause of death of cancer patients is growth and metastasis of their tumors. By targeting signal transduction pathways as sites of therapeutic intervention, we have identified a novel anticancer drug carboxyamidotriazole (CAI). A straight-forward and reliable method of detection and quantitation of human CAI plasma levels using solid-phase organic extraction followed by isocratic reversed-phase chromatography is now reported. This assay detected CAI over the concentration range 0.04-10.0 micrograms/ml, which brackets the range shown to be physiologically and biochemically effective. Linearity was demonstrated by linear regression analysis of calibration curves (r2 = 0.999). Equivalence of recovery of extracted versus non-extracted CAI over a broad concentration range was demonstrated (r2 = 0.998, coefficients of variability < 10%). The method was applied to quantitate CAI plasma levels from patients now entered on the Phase I clinical trial underway at the National Cancer Institute. PMID- 8491820 TI - Purification of growth hormones by reversed-phase high-performance liquid chromatography. AB - Reversed-phase high-performance liquid chromatography (HPLC) on a column of Radial-Pak C18 cartridge was utilized for the purification of a variety of growth hormone (GH) proteins from mammalian, avian, amphibian and fish pituitary glands. Recovery of GH from pituitary glands of up to 0.43% of total protein was obtained with a high degree of homogeneity as revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The HPLC-purified GHs show reactions of identity or near identity by immuno-diffusion studies on agar gel. This method offers a convenient and rapid purification of vertebrate GH on an analytical or preparative scale. PMID- 8491821 TI - Quantitation of benzoylnorecgonine and other cocaine metabolites in meconium by high-performance liquid chromatography. AB - A method for simultaneous extraction of cocaine and metabolites benzoylnorecgonine, benzoylecgonine and norcocaine from meconium was developed. The procedure uses solid-phase extraction columns with both cation-exchange and hydrophobic properties after vortex-mixing meconium with methanol. Chromatography utilizes reversed-phase high-performance liquid chromatography with a C18 column and phosphate buffer-acetonitrile as mobile phase. The method is specific and sensitive to 50 ng/g meconium for all compounds. Standard curves are linear from 0.05 to 5.0 micrograms/g (r2 > or = 0.989). Intra-assay coefficients of variation were < or = 6.9%. Meconium from infants exposed to cocaine in utero contained varying combinations of the four drugs. PMID- 8491822 TI - Determination of 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)-dodecanamide, a lipid regulator, in rat plasma and mesenteric lymph by reversed-phase high-performance liquid chromatography. AB - 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (I, CI-976) has been determined in rat mesenteric lymph and plasma using a rapid and sensitive high performance liquid chromatographic method. The samples prepared from plasma and lymph by liquid-liquid extraction were analysed on a reversed-phase C18 column isocratic conditions and ultraviolet detection. The method was applied to the determination of levels of I in Wistar rats after intraduodenal administration of 110 mg/kg of I as a lipid emulsion. PMID- 8491823 TI - Simultaneous determination of dapsone, monoacetyldapsone and pyrimethamine in whole blood and plasma by high-performance liquid chromatography. AB - A sensitive, selective and rapid reversed-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of dapsone, monoacetyldapsone and pyrimethamine in human whole blood and plasma. The procedure involved extraction of the compounds and the internal standard, monopropionyldapsone, with tert.-butylmethyl ether under alkaline conditions. A newly marketed column, Supelcosil LC-ABZ (Supelco, 15 cm x 4.6 mm I.D.), was employed. The mobile phase, consisting of acetonitrile-methanol-phosphate buffer (2:1:7, v/v/v), was delivered at a flow-rate of 1.2 ml/min, and ultraviolet absorbance was monitored at 286 nm. The limit of determination using a 150 microliters sample was 10 ng/ml (40 nM) for dapsone and pyrimethamine and 8 ng/ml (28 nM) for monoacetyldapsone. Given that only a small amount of blood is required in this method, it could now be applied in studies involving blood level monitoring and pharmacokinetics in children on Maloprim (dapsone-pyrimethamine) prophylaxis in malaria endemic areas. PMID- 8491824 TI - High-performance liquid chromatographic method for the determination of the anthelmintic nitroxynil in cattle muscle tissue with on-line anion-exchange clean up. AB - A high-performance liquid chromatographic method for the determination of the anthelmintic nitroxynil has been developed. The drug was extracted from cattle muscle tissue with 1% triethylamine in acetonitrile. The extract was evaporated to dryness and taken up in 0.1 M ammonium acetate-acetonitrile (50:50, v/v). The extract was then injected onto a polymeric anion-exchange precolumn. After clean up with 0.1 M ammonium acetate-acetonitrile (50:50, v/v) for 5 min, the precolumn was eluted with 1% aqueous trifluoroacetic acid-acetonitrile (50:50, v/v) onto a PLRP-S polymer column and chromatographed with a mobile phase of 0.01 M phosphate pH 7-acetonitrile (80:20, v/v). Detection was by ultraviolet at 273 nm. Average recoveries at four levels from 0.005 to 1.000 mg kg-1 were > 88%. The limit of determination was 0.005 mg kg-1. PMID- 8491825 TI - High-performance liquid chromatographic method for the determination of the dinitrocarbanilide component of nicarbazin in eggs with on-line clean-up. AB - A high-performance liquid chromatographic method for the determination of the dinitrocarbanilide component of the anti-coccidial drug nicarbazin has been developed. The drug was extracted from egg with acetonitrile. The extract was evaporated to dryness and taken up in water-acetonitrile (80:20, v/v). The extract was then injected onto a reversed-phase precolumn. After clean-up with 20% aqueous acetonitrile for 5 min, the precolumn was eluted onto a Chromspher C18 cartridge column with 0.01 M potassium dihydrogen-phosphate pH 4.0 acetonitrile (50:50, v/v). Detection was by ultraviolet at 343 nm. Average recoveries at five levels from 0.005 to 0.500 mg kg-1 were > 80%. The limit of determination was 0.005 mg kg-1. PMID- 8491826 TI - Determination of nalmefene in plasma by high-performance liquid chromatography with electrochemical detection and its application in pharmacokinetic studies. AB - A method for measuring human plasma levels of nalmefene after oral and intravenous administration is presented. The method consists of a solid-phase extraction procedure followed by HPLC analyses. A cyanopropyl column is used for the solid-phase extraction and 60% (v/v) acetonitrile in dilute sodium pentanesulfonic acid solution for elution. The concentrated and filtered eluate is injected into the HPLC system, which is equipped with an electrochemical dual electrode detector. A phenyl column is used in this HPLC system with a mobile phase containing 30% (v/v) acetonitrile in dilute sodium pentanesulfonic acid solution. A signal-to-noise ratio of 4.5 is obtained when a 1 ng/ml spiked plasma sample is analyzed. To determine the applicability of this method for human pharmacokinetic studies, nalmefene levels in plasma were measured at time points up to 24 h following oral and intravenous administration of 30 mg of nalmefene hydrochloride to two subjects. These studies demonstrated that the proposed method is sufficiently sensitive to study the pharmacokinetic profile of nalmefene in man. PMID- 8491827 TI - Sensitive liquid chromatographic method for the determination of a specific M1 agonist, LY246708, an investigational agent with potential for the treatment of Alzheimer's disease, in human plasma. AB - A reversed-phase HPLC method is reported for the determination of a new M1 agonist, LY246708, in human plasma. The compound and an internal standard were extracted from plasma with hexane at basic pH. The organic extract was evaporated to dryness and the residue was reconstituted with mobile phase [0.5% diethylamine (pH 3, adjusted with phosphoric acid)-acetonitrile (70:30, v/v)]. The analytes were separated from endogenous substances on a Zorbax CN column; the effluent was monitored by measuring its absorbance at 296 nm. The limit of quantification was determined at 1.5 ng/ml and the response was linear from 1.5 to 20 ng/ml. Validation studies showed the method to be both repeatable and reproducible. Its robustness was demonstrated by transfer between analytical laboratories and continued use in support of pharmacokinetic studies and therapeutic monitoring of the compound. PMID- 8491828 TI - Multichannel coulometric detection coupled with liquid chromatography for determination of phenolic esters in honey. AB - A method for the determination of phenolic esters in different varieties of honey was developed. The substances were separated by RP-HPLC. A coulometric electrode array system with sixteen electrodes arranged in series and set at increasing potentials (300-900 mV) was used for electrochemical detection of the compounds. Chromatographic peaks for methyl 4-hydroxybenzoate, methyl vanillate, methyl syringate, trans-p-methyl coumarate and trans-methyl ferulate were identified. The content of the esters varied between 1.3 and 5044 micrograms per kg of honey with detection limits of 0.1-1.0 microgram per kg of honey (S/N = 3). The method described is a sensitive assay to differentiate between rape honey and other varieties. PMID- 8491829 TI - Analysis of phenolic and flavonoid compounds in juice beverages using high performance liquid chromatography with coulometric array detection. AB - Analysis of phenolics and flavonoids in juice beverages using reversed-phase HPLC with coulometric array detection is described. Sixteen serial coulometric detectors were used for on-line resolution of co-eluting compounds and generation of voltammetric data. Within each class of compounds, oxidation potential corresponded to specific substitution patterns where: catechol < methoxycatechol < monohydroxyl < methoxyl. Twenty-seven standard compounds were resolved in a 45 min run. The limits of detection were in the low ng/ml range with a linear response range of at least three orders of magnitude. Intra-run retention time variation was < 1% (R.S.D.) and adjacent sensor response ratios varied by < 5% (R.S.D.). The utility of this technique in generating multivariate data for differentiation of juices and juice mixtures is shown. PMID- 8491830 TI - Chemical reduction of FD&C yellow No. 5 to determine combined benzidine. AB - Data are presented suggesting the presence of the aromatic amine benzidine as a combined impurity in the regulated color additive FD&C Yellow No. 5. The benzidine exists as an azo-dye constituent that forms from free benzidine impurities introduced during the manufacture of the color additive. The presence of combined benzidine is ascertained by sodium dithionite reduction of the azo bonds in the commercial color additive. The resulting reduction products are extracted with chloroform, and the liberated benzidine is determined by high performance liquid chromatography (HPLC). The levels of benzidine determined by HPLC exceed those levels of benzidine accounted for by direct determination of free aromatic amines in the unreduced color. PMID- 8491831 TI - High-performance liquid chromatographic determination of PZ-peptidase activity. AB - A rapid and sensitive assay method for the determination of PZ-peptidase activity is reported. This method is based on the monitoring of the absorption at 320 nm of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu (PZ-Pro-Leu), enzymatically formed from the substrate 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ peptide), after separation by high-performance liquid chromatography using a C18 reversed-phase column by isocratic elution. This method is sensitive enough to measure PZ-Pro-Leu at levels as low as 10 pmol, yields highly reproducible results and requires less than 5.5 min per sample for separation and determination. The optimum pH for PZ-peptidase activity was 7.5-8.0. The Km and Vmax values were 166.7 microM and 5.35 pmol/min.microgram protein, respectively, with the use of enzyme extract obtained from mouse whole brain. The approximate molecular mass of this enzyme was estimated to be 64,000 by gel filtration. PZ peptidase activity was strongly inhibited by Zn2+, Cu2+ and p chloromercuriphenylsulphonic acid. By using this method, PZ-peptidase activity could be readily detected in a single mouse pituitary gland. Among the tissues examined in various mouse brain regions, the highest specific activity of the enzyme was found in cerebral cortex. The sensitivity and selectivity of this method will aid in efforts to examine the physiological role of this peptidase. PMID- 8491832 TI - Optimized separation of purine bases and nucleosides in human cord plasma by capillary zone electrophoresis. AB - An optimized separation of the main purine compounds of human serum by capillary zone electrophoresis is presented. Separations were performed in an uncoated silica capillary (44 cm x 75 microns I.D., 37 cm to window) on a SpectraPhoresis 1000 system with UV detection. The separation of adenine (Ade), adenosine (Ado), guanine (Gua), guanosine (Guo), hypoxanthine (Hyp), inosine (Ino), xanthine (Xan) and uric acid (UA) was optimized with respect to pH, temperature, applied potential and hydrodynamic injection time. Optimum conditions were 20 mM borate buffer (pH 9.4), 37 degrees C, 20 kV and 9 s load and detection at 260 nm. Linearity extended from 1 to 125 microM. The sensitivity of the method was 0.5 microM, which is adequate for measuring Ade, Gua, Hyp and UA in plasma samples. Plasma samples from newborns were precipitated with an equal volume of perchloric acid (7%, v/v), the supernatant was adjusted to neutral pH with potassium carbonate and, before injection, the sample was alkalized with sodium hydroxide. The method presented here allows the determination of Ade, Guo, Hyp and UA. The levels of the determined purines were compared in samples from control newborns, preterm babies and newborns with asphyxia or acidic serum pH values. PMID- 8491833 TI - Strategies for the monitoring of drugs in body fluids by micellar electrokinetic capillary chromatography. AB - Electrokinetic capillary techniques can exploit numerous separation principles, making them flexible and easily applicable to a variety of separation problems. In recent publications, this emerging technology has been shown to be well suited for monitoring drugs and metabolites in body fluids, including serum, saliva and urine. Most attention has been focused on micellar electrokinetic capillary chromatography (MECC) because it permits the separation and determination of drugs with discrimination being largely based on differences in hydrophobicity. An overview of literature data on the MECC of drugs in body fluids and recent data obtained with antiepileptics in serum and saliva, with model mixtures of illicit drugs, and with extracts from urine specimens that tested positively for opiates and cocaine metabolites are presented. Emphasis is focused on buffer selection and simple sample preparation procedures, including direct injection of body fluids, ultrafiltration and solid-phase extraction. PMID- 8491834 TI - Differential binding of tioconazole enantiomers to hydroxypropyl-beta cyclodextrin studied by capillary electrophoresis. AB - Capillary electrophoresis has been used to determine binding constants of tioconazole enantiomers with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), after correcting for changes in mobility with increasing viscosity. The predicted and observed values of enantiomeric mobility difference were found to be maximum at a concentration of HP-beta-CD equal to the reciprocal of the average binding constant. PMID- 8491835 TI - Comparison of capillary zone electrophoresis with high-performance liquid chromatography for the determination of additives in foodstuffs. AB - A capillary zone electrophoretic (CZE) method was developed to determine caffeine, aspartame and benzoic acid in diet cola soft drinks and in artificial sweetening powders. The effects of pH, ionic strength, organic solvents and different buffers were investigated to select the optimum conditions. These consisted of a sodium phosphate buffer at pH 11 and ionic strength 0.025. The running voltage was set at 15 kV and the injection was performed hydrostatically for 30 s. The CZE method was then compared with a previously developed high performance liquid chromatographic (HPLC) method in terms of repeatability, reproducibility, accuracy, linearity, sensitivity and separation efficiency. Both methods gave good repeatability. The relative standard deviations for reproducibility were significantly higher in CZE than in HPLC. The main reason for this is probably the condition of the wall of the capillary, which was difficult to keep constant between the days of analysis. The separation efficiency of CZE was 65-110 times higher than that of HPLC; on the other hand, 10-20 times lower detection limits were obtained in HPLC. Both methods were linear, but the linear ranges were different owing to the lower detection limit of HPLC. In CZE, the effect of the matrix was higher. PMID- 8491836 TI - Manipulation of electroosmotic flow in capillary electrophoresis. AB - This paper reports the use of surfactant and polymer-C18 coated capillaries that allow manipulation of electroosmotic flow (EOF). Although this approach to the control of EOF involves the preparation and use of multiple capillaries, all the coatings were prepared by a single procedure. It is shown that the ability to control EOF allows optimization of both separation time and resolution. In the case of proteins, low EOF maximizes resolution whereas high flow gives the shortest analysis time. It should be noted that proteins are a special case and this conclusion may not be true with other molecular species. Through selection of a specific coating, it is possible to complete a separation in the shortest time while maintaining sufficient resolution to give baseline resolution of proteins. The various coated capillaries were examined in capillary zone electrophoresis (CZE) and capillary isoelectric focusing (cIEF) separations of native protein standards and hemoglobin variants. Separation of glycosylated hemoglobin A1 variants was achieved by cIEF within 10 min, including the focusing time. Good run-to-run reproducibility was obtained by flushing the capillary with the coating solution between analyses. PMID- 8491837 TI - Monitoring tripeptidase activity using capillary electrophoresis. Comparison with the ninhydrin assay. AB - Capillary electrophoresis (CE) was used to assay the activity of a tripeptidase from a crude extract of Lactococcus lactis subsp. lactis NCDO 712 against the substrate, Gly-Gly-Phe and a comparison with a standard ninhydrin assay was made. Standard curves of the substrates and products showed a significantly variable colorimetric reaction to ninhydrin making accurate quantification of the tripeptidase problematic. The CE assay further demonstrated that the presence of contaminating enzymes in crude cell-free extracts can cause secondary reactions that are not apparent from the ninhydrin assay data. The CE assay was also able to generate enzyme kinetics data and monitor, during purification, the presence of co-eluting contaminating activities. The speed and sensitivity with CE allows routine analysis of the tripeptidase activity without any derivatization normally required for this enzyme. PMID- 8491838 TI - Separation and tryptic digest mapping of normal and variant haemoglobins by capillary electrophoresis. AB - Characterization of haemoglobin (Hb) through whole protein separations and tryptic digest mapping allows the identification of structural Hb variants which result in haemoglobinopathies. Tryptic digest mapping by conventional two dimensional paper chromatograph-electrophoresis provides high resolution but requires 48 h, while gradient elution reversed-phase high-performance liquid chromatography (HPLC) is faster (1.5 h), there is decreased resolution. CE analysis provides a fast separation with high resolution. We have used CE to optimise the tryptic digestion of globin purified from normal human haemoglobin A and to analyze tryptic digests from normal Hb. The separations were optimised and peak identification performed using UV scanning detection. In the optimised tryptic digest separation up to 28 peaks could be resolved in < 20 min. These peaks were identified as far as possible and a high-resolution map of the digest was constructed. The optimised analytical conditions were used to observe the separation pattern obtained from normal adult haemoglobin (HbA), common variant haemoglobins and some rarer haemoglobin variants. PMID- 8491840 TI - Comparison of selectivities of reversed-phase high-performance liquid chromatography, capillary zone electrophoresis and micellar capillary electrophoresis in the separation of neurohypophyseal peptides and analogues. AB - A number of RP-HPLC systems, including those prescribed in several official monographs, have been evaluated for separating oxytocin, the vasopressins, some clinically important analogues and two additional neurohypophyseal nonapeptides. The separation has been compared with capillary zone electrophoresis and micellar electrophoresis in four micellar systems: cationic, anionic, zwitterionic and neutral. Complete separation was achieved by both RP-HPLC and micellar CE but the importance of charge as a major parameter of separation in CE confers a distinct and useful selectivity to micellar CE based separations. PMID- 8491839 TI - Identification of gonadorelin (LHRH) derivatives: comparison of reversed-phase high-performance liquid chromatography and micellar electrokinetic chromatography. AB - A number of reversed-phase (RP) HPLC systems for the separation of gonadorelin (gonadoliberin, LHRH) and five therapeutically important analogues have been systematically examined. The selectivity of RP-HPLC has been compared with several micellar electrokinetic chromatographic (MEKC) systems and free solution capillary electrophoresis. RP-HPLC exhibits greater selectivity towards structural differences, but complete separation of the peptides in one isocratic analytical run is tedious due to the large differences in retention. Gradient elution gives satisfactory separation in an acceptable time span. Of the micellar systems examined (sodium dodecyl sulphate, cetrimide, 3 [(cholamidopropyl)dimethylamino]-1-propanesulphonate and Triton X-100) only MEKC with cetrimide micelles gave a complete separation showing selectivity similar, but not identical, to RP-HPLC, and providing a complete separation of all six compounds as rapidly as gradient RP-HPLC. PMID- 8491841 TI - Re-examining handedness in schizophrenia: now you see it--now you don't. AB - The present study was designed to examine patterns of handedness across tasks (i.e., those requiring less vs. greater skill) and over time (initially and 1 month later) in 72 schizophrenic patients and 105 normal controls. Two important methodologic advances were introduced: (1) two handedness tasks, varying in skill level (simple vs. complex); and (2) the addition of a retest on both tasks, 1 month later. Results show a higher incidence (43%) of mixed handedness in the schizophrenic sample than in normal controls (14.3%) on tasks requiring less precision in performance. Similar results were obtained when schizophrenic patients were retested 1 month later, RI = .88. When the more demanding set of tasks was presented, the frequency of mixed handed schizophrenics dropped by 50% at initial testing. Despite these findings, there was no evidence for stability of change over time. For example, each of the most extreme shifters at Time 1 was fully lateralized 1 month later. PMID- 8491842 TI - Complex figure recall in the elderly: a deficit in memory or constructional strategy? AB - Spatial memory declines with age. This study investigated the hypothesis that the decline in spatial memory in the elderly is due to a dysfunction in frontal lobe mediated planning and organization. The copy and recall ability of 49 elderly subjects and 20 younger subjects was assessed using the Rey-Osterrieth Figure. In addition, the manner of construction, (e.g., the order that each line was produced) was compared between groups. Despite comparable performance with the younger subjects when copying the figure, older subjects performed significantly worse than younger subjects when asked to reproduce the figure from memory. However, this was not due to the organizational strategies they used while copying the figure. They constructed the figure in the same manner as the younger subjects. Therefore, the spatial memory deficits in the elderly are not due to an abnormal organizational strategy. These results are discussed in relation to those of patients with frontal lobe damage and preliminary data from subjects with mild dementia. PMID- 8491843 TI - Assessment of malingering after mild head trauma with the Portland Digit Recognition Test. AB - The Portland Digit Recognition Test (PDRT), a forced-choice measure of recognition memory designed for the purpose of assessing the possibility of malingering, was administered to two groups of clinically referred patients seeking financial compensation for injuries including a mild head trauma group and a brain dysfunction group and also to a third group with brain dysfunction not seeking compensation. The three groups were equated on verbal acquisition ability. The two groups seeking remuneration were impaired on the PDRT compared with the group not seeking compensation, and the brain dysfunction group seeking compensation was superior to the mild head trauma group. Cut-off scores were established for the group with brain dysfunction not seeking compensation, and 33% of the mild head trauma group and 18% of the brain dysfunction group seeking compensation fell below the cut-offs. Significantly below chance scores were found in 17% and 3% of the two groups seeking compensation, respectively. Difficult PDRT items were more sensitive than easy items to compensation-related deficit. The PDRT is recommended as a measure of exaggeration of memory deficits. PMID- 8491844 TI - Reliability of the Lateral Dominance Examination. AB - The reliability of the Lateral Dominance Examination over a 5-year period was evaluated in 162 normal and neurologically impaired adults. Stability of individual test items was appraised as well as that of summary measures of handedness, eyedness, and footedness. Items evaluating handedness rendered highly consistent results with the most reliable item relating to hand used for writing (100%). Eyedness and footedness items were somewhat less reliable. While the data raised the possibility that non-right-handers may be slightly less consistent over time, membership in a neurological group, extent of impairment on neuropsychological tests, and gender were unrelated to consistency in lateral preference measurement. It is concluded that the Lateral Dominance Examination is a reliable measure of lateral preference. PMID- 8491845 TI - CT scan cerebral hemispheric asymmetries: predictors of recovery from aphasia. AB - Individual variations in anatomic cerebral asymmetries have been linked with specific neurodevelopmental processes, with patterns of cognitive ability, and with recovery from focal brain damage. The present study investigated relationships between cerebral asymmetries and recovery from aphasia. Aphasic patients (N = 25) were assessed for language recovery for 1 year poststroke, and linear measurements of cerebral asymmetries were performed on CT scans. Increasing left occipital width asymmetry was associated with faster rate of language recovery and with higher final language scores during the first year poststroke. There was, moreover, a tendency for increasing left occipital width asymmetry to be associated with less initial impairment. It is hypothesized that those aspects of neural organization conferring better premorbid language skills are the same factors conferring greater recovery of language skills and that occipital width asymmetry serves as a marker for such individual differences in neural organization. PMID- 8491846 TI - Longitudinal outcome for low birth weight infants: effects of intraventricular hemorrhage and bronchopulmonary dysplasia. AB - This study addresses the mental and motor development of 78 low birth weight infants (LBW) classified into five groups according to early medical complications: (1) respiratory distress syndrome (RDS); (2) intraventricular hemorrhage (IVH Grades I-II); (3) IVH (Grade III); (4) IVH (Grade IV) with hydrocephalus; and (5) bronchopulmonary dysplasia (BPD) with or without IVH. Each child received an assessment of mental and motor development at 6, 12, 24 and 36 months of age. Results of mental scores revealed clear effects of group and age, but no interaction of group and age. The RDS and IVH (Grades I-III) groups generally had higher scores on indices of mental development than did IVH (Grade IV) and BPD infants with or without IVH. Although most groups had higher mental scores at the older ages, rates of growth were essentially parallel across the five groups. There was some support for differential rates of motor development, with the IVH (Grade IV) group showing acceleration between 24 and 36 months of age while the BPD group continued to show motor delay at 36 months. These results call into question the common practice of correcting psychology test scores of LBW infants for gestational age. PMID- 8491847 TI - Transfer of new learning in memory-impaired patients. AB - Previous research has produced conflicting evidence concerning transfer of new learning by amnesic patients. The present experiment investigated the hypothesis that different numbers of learning trials account for differences in transfer, such that the greater the number of repetitions of material in identical stimulus contexts the poorer the transfer. Six memory-impaired patients and six control subjects attempted to learn the names of business-related documents in response to descriptive definitions. Learning continued until one of the following criteria was reached: 50% correct, 100% correct, 100% correct plus 10 trials. In a transfer task, subjects were then asked to produce the target responses to altered definitional cues. The results of the experiment demonstrated that, contrary to prediction, transfer improved with numbers of learning trials. Results are consistent with the view that continued study of information allows better integration of new learning with prior knowledge and correspondingly higher levels of transfer. The theoretical implications of the findings are discussed in terms of the declarative/procedural and the episodic/semantic memory distinction. It is suggested that memory-impaired patients are capable of acquiring new semantic information although not at a normal rate. Implications for memory rehabilitation are also outlined. PMID- 8491848 TI - Anosognosia in Alzheimer's disease: relationships to depression, cognitive function, and cerebral perfusion. AB - Awareness of memory loss was rated in 57 patients with clinically diagnosed Alzheimer's disease, and analyzed in relation to neuropsychological tests and presence of depression. Single photon emission computed tomography measures of regional cerebral blood flow were obtained on an unselected subsample of 20. Anosognosia was associated with diminished relative right dorsolateral frontal lobe perfusion and with high rates of false positive errors on recognition memory testing. Less aware patients did not differ from others on learning or recall scores, or on dementia severity as measured by mental status scores. Neither anosognosia nor depression was associated with disease duration or dementia severity and patients who were aware of their memory loss were no more likely than others to be depressed. This is further evidence that dementia severity alone does not account for anosognosia in Alzheimer's disease; frontal lobe involvement and the presence of specific memory impairments may be important determining factors. PMID- 8491849 TI - Forgetting rates for verbal, pictorial, and figural stimuli. AB - Literature on forgetting rates is reviewed and related methodological issues are discussed. Descriptive data from 50 subjects are provided for tests which were developed to assess forgetting rates for words, pictures and designs. The three tests are well-matched on initial learning at criterion and have comparable variance and skewness of score distributions. Forgetting rates were similar across the initial 10-min retention interval, but there was a more rapid loss of words than pictures and designs from 10 min to 2 hr, especially in male subjects. Memory for words and pictures steadily declined between 10 min and 48 hr, but there was no further loss for designs after 2 hr. These findings suggest that nonverbal memory storage is more stable than verbal memory storage over intervals of hours to days. Modest sex differences are discussed in terms of potential differences in organization of brain function. The potential utility of these tests in further elucidating the nature of memory impairment in clinical populations is addressed. PMID- 8491850 TI - Executive function in Parkinson's disease: set-shifting or set-maintenance? AB - In order to distinguish impairment in set-shifting in Parkinson's disease (PD) from inability to inhibit distraction by stimuli that compete for attention, 18 nondemented patients with idiopathic PD and 13 normal controls equated for age and education, were administered the Odd-Man Out (OMO) test and the Stroop Color Word Test. PD patients were significantly impaired on the OMO test but showed no evidence of interference during the Stroop test. Analysis of error patterns during the OMO test indicated that the requirement to repeatedly switch rules, rather than the requirement to maintain steady responding between rule switches, was responsible for impaired OMO performance. It is concluded that the OMO test is fundamentally a test of set shifting, rather than a test of set maintenance in PD. In addition, analysis of a larger sample of PD patients revealed a significant positive relationship between number and severity of extrapyramidal signs and error production on the OMO, and between the latter and global mental function. These relationships were independent of each other, suggesting that impairment in set-shifting function in PD may arise from pathology of the fronto striatal system independently of changes in cognitive ability. PMID- 8491851 TI - Category-specific form-knowledge deficit in a patient with herpes simplex virus encephalitis. AB - In-depth case study of a herpes simplex virus encephalitis patient who presents with a relatively clear knowledge disorder and anterograde amnesia in the absence of any other major cognitive deficit. The main neuropsychological feature is a category-specific impairment restricted to living things. The patient misnamed pictures of animals and vegetables, could not accurately draw animals from memory or verbally describe their visual appearance, and was not accurate in sorting pictures of real animals from pictures of unreal animals; conversely, in the same tasks her performance with artifactual objects was either errorless or superior to that with animals. We interpret the patient's category-specific deficit as due to a selective disturbance within the structural description system, rather than a deficit in low-level visual processing or semantic memory. From this case study and a review of other reported cases we claim that such deficit of form-knowledge is a consequence of the extensive lesions that affect bilaterally the inferior parts of the temporal lobes. The patient here described thus offers further empirical evidence for the crucial role of the inferotemporal cortex in processing visual knowledge about concepts. PMID- 8491852 TI - Diurnal oscillations in hemispheric performance. AB - Folkard (1979, 1990) suggested that diurnal changes in performance may reflect a morning-evening decrease in the degree of left-hemisphere dominance. Forty-eight right-handed women performed verbal and spatial hemifield tachistoscopic tasks at four separate times of day. Supporting the above hypotheses, changes in accuracy over the day showed a left-hemisphere advantage at 12:00 and a right-hemisphere advantage at 19:45, whereas changes in speed were symmetrical both in verbal and spatial tasks. These changes occurred only when hemispheres received stimuli in the processing of which they were not specialized, that is, when verbal stimuli appeared at the left visual field and spatial stimuli at the right visual field. Evidence suggesting a separate oscillatory control of the circadian rhythms of left and right-hemisphere activity is discussed. PMID- 8491853 TI - Speed of memory scanning is not affected in early HIV-1 infection. AB - Thirty-seven nondemented HIV-seropositive and 17 seronegative control subjects were administered the Sternberg speed of memory scanning task, a procedure frequently employed to study mental slowing in patients with subcortical dementing disorders. Experimental and control subjects did not differ in speed of memory scanning, as indexed by the slopes of set size-reaction time functions, nor on mean 0-intercepts for the RT functions, which index stimulus detection and motor response time. Intercept values were significantly greater for subjects with a positive alcohol abuse history and for subjects with greater self-reported depression, but slopes were not significantly correlated with substance abuse history or psychological distress. Cognitive slowing in early HIV-1 infection is not a nonspecific effect observed across all measures of information processing speed. Underlying component functions measured must be carefully considered when selecting reaction time tasks for study with HIV-seropositive subjects. The term "subcortical" dementia may be too general a descriptor, and RT task performance may provide an alternative basis for classification of dementia types. PMID- 8491854 TI - Three-word recall as a measure of memory. AB - Clinical examination of memory functions often includes the administration of simple free recall tasks, such as the recall of several words following a few minutes. Little is known, however, about the normative parameters or psychometric properties of such procedures, and such techniques have rarely been compared with more comprehensive, well-standardized memory indices. To address these issues, two three-word recall tasks were administered to a large group of carefully selected healthy subjects over the age of 50 years. The Mini-Mental State Examination (MMSE) was obtained as an index of global cognitive status, and the California Verbal Learning Test (CVLT) was used to exclude subjects with abnormal memory abilities. Significant but modest relationships were found between two three-word recall tasks and CVLT results. Substantial variability was seen on three-word recall, with a significant proportion of normal subjects recalling zero or one word. Results suggest using caution in interpreting simple recall performance as an index of memory, as great variability in results is seen among healthy (particularly older) individuals. PMID- 8491855 TI - Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP). AB - The obstructive sleep apnea syndrome is characterized by nocturnal sleep disturbance, excessive daytime sleepiness and neuropsychological deficits in the areas of memory, attention, and executive tasks. In the present study, these clinical manifestations were assessed in apneic patients before and 6 months after treatment with nasally applied continuous positive airway pressure (CPAP). CPAP treatment was found to restore normal respiration during sleep and to normalize sleep organization. Daytime vigilance greatly improved with treatment but some degree of somnolence as compared to normal controls persisted. Similarly, most neuropsychological deficits normalized with treatment. The exception was for planning abilities and manual dexterity, two neuropsychological deficits that have been found to be highly correlated with the severity of nocturnal hypoxemia. These results raise the possibility that anoxic brain damage is a pathogenic factor in severe obstructive sleep apnea syndrome. PMID- 8491856 TI - Basic mechanisms of constructional apraxia in unilateral brain-damaged patients: role of visuo-perceptual and executive disorders. AB - The basic mechanisms of constructional apraxia (CA) are still a matter of debate. In this study we assessed the possible relationships between CA and performance on tasks assessing visual perception, low-level motor skill, manipulo-spatial ability, and general intellective efficiency in samples of healthy subjects, right-brain-damaged (RBD) and left-brain-damaged (LBD) patients. Multiple regression analyses, performed separately for the three groups, demonstrated that efficiency in perceiving the model as a whole is the factor mainly related to drawing performance of normal subjects. In the RBD group, instead, a disorder of the manipulo-spatial ability seems to play the most important role in producing CA. As for the LBD group, the most relevant finding is that patients drawing with the left hand are significantly more impaired than patients using the right hand and than control subjects. These results are discussed in relation to various hypotheses so far advanced to account for basic mechanisms of CA in unilateral brain-damaged patients. PMID- 8491857 TI - A technique for diagnosing the individual patterns of innervation of the trapezius muscle prior to neck dissection. AB - Based on the techniques of regional anaesthesia, a method for simulating the effects of radical neck dissection on the innervation of the trapezius muscle by selectively and reversibly blocking the accessory nerve and its superficial cervical anastomoses, was developed and tested on 40 patients who were due to undergo radical neck dissection. Action potentials of the three portions of the muscle were recorded after this blockade as well as after radical neck dissection, and compared. It was found that the electromyograms were congruent in 92.5% of the cases. Four patterns of innervation were demonstrated, ranging from complete substitution of the resected or blocked nerves to a remaining muscle activity of less than 20% after blockade or radical neck dissection. PMID- 8491858 TI - Assessment of tumorous mandibular involvement by transcutaneous ultrasound and flexible endosonography. AB - Tumorous involvement of the mandible affects the prognosis and choice of treatment. To evaluate the usefulness of transcutaneous ultrasound and recently developed flexible endosonography and their ability to display bone invasion in the lower jaw, we studied 33 non-selected patients with extensive, histologically verified oral and oropharyngeal carcinomas. Both sonographic examinations were performed prospectively in all patients prior to surgery, without knowledge to the sonographer of the results of other imaging methods. Histological findings served as gold standards and offered 14 mandibular involvements. Flexible endosonography is characterized by high accuracy data in assessment of mandibular involvement occurring in tumors of the floor of the mouth and of the tonsil. On the other hand acceptable results by transcutaneous ultrasound could only be obtained in assessing bone invasion of oral tumors. However, osseous destruction in patients with oropharyngeal tumors were not detectable as the involved medial surface of the mandibular ramus was inaccessible to the extraorally placed transducer. Both sonographic methods, especially endosonography, enabled the examiner to differentiate cortical bone as opposed to spongiosa involvement in many cases, but failed in assessment of tumorous periosteal involvement. Pitfalls in detection and differentiation of bone invasion with false positive and false negative findings are discussed with regard to mandibular anatomy, for both intra and extraoral examination. PMID- 8491859 TI - Fixation of vascularized bone grafts. AB - In 24 patients, fixation of isolated or combined bone grafts has been performed exclusively with miniplates. Other than the lateral displacement of one osteomyocutaneous iliac crest graft, no complication occurred with regard to the fixation method chosen. In contrast to the clinical findings, our results of an animal experiment demonstrate less complications by fixation of vascularized bone grafts to mandibular angle defects (guinea pig) when THORP plates are used instead of miniplates. Whereas we consider miniplate fixation of vascularized bone grafts to be the method of choice, selected patients may require more stable fixation systems, especially when a high postoperative mobility may be expected or large amounts of the mandible including the condyle have to be reconstructed. PMID- 8491860 TI - Comparative evaluation of different radiographic projections of zygomatic complex fractures. AB - Diagnosis of zygomaticomaxillary fractures is a major problem in radiographic interpretation. The purpose of the present study was to evaluate several radiographic examinations performed in an emergency room to diagnose zygomatic complex (ZC) fractures, in order to determine which is the single best radiographic projection for this purpose. Radiographs of 160 patients with ZC fractures were evaluated retrospectively. The modified P-A projection (10 degrees 20 degrees) provided a clear image of the frontozygomatic, infra-orbital rim and temporozygomatic fracture lines in all cases. In half the cases, the modified P-A projection also clearly demonstrated the fracture line in the zygomatic maxillary buttress. On the other hand, the Water's view demonstrated the fracture line in the zygomatic maxillary buttress and the temporozygomatic bone in all cases, but in only 65% of the cases was the fracture line in the infra-orbital rim and the frontozygomatic bones shown. The modified P-A projection was found to be the single best radiographic examination that should be performed in the emergency room to diagnose ZC fractures. PMID- 8491861 TI - Well-differentiated liposarcoma mimicking a pleomorphic lipoma--a case report. AB - A case of well-differentiated liposarcoma with floret-like multinucleated giant cells in a 59-year-old woman who presented with supraclavicular mass is described. On the biopsy section, the mass had an appearance consistent with a pleomorphic lipoma. Multiple microscopic sections revealed the pathognomic features of a well-differentiated liposarcoma. PMID- 8491862 TI - Histology of laser- and high-frequency-electrosurgical incisions in the palate of pigs. AB - The histological effects of CO2-laser-, Nd-YAG-laser- and electrosurgical incisions were investigated in the oral mucosa of pigs. Laser- as well as electrosurgery caused necrosis by thermal effects. Undermining vacuolisation in the stratum basale and denaturation of collagenous fibers in the lamina propria were typical findings. The CO2-laser incisions were trough-like with a sharply bordered coagulation. The Nd-YAG-laser produced exclusively coagulation but no incision. Electrosurgery yielded radiating coagulation and the best ratio of depth of incision to width of coagulation. PMID- 8491863 TI - Hibernoma: unusual location in submental space. PMID- 8491864 TI - Strip ostectomy and radical ostectomy in the treatment of craniosynostosis. An experimental animal study. AB - In an experimental animal study using rabbits, growth phenomena were simulated which are comparable to craniosynostosis in humans. The radiological and histological findings after surgical management of these artificial craniosynostosis by means of strip ostectomy or radical ostectomy were compared with the findings obtained in control animals. Following strip ostectomy, bone defects were rapidly filled by the formation of suture-like structures. After radical ostectomy, structures consisting of connective tissue dispersed among islands of ossification were preserved over a considerable period of time, making it possible for the calvarium to adapt to the fast-growing brain. In contrast to strip ostectomy, after radical ostectomy growth of both the neurocranium and the viscerocranium, as well as the total sagittal growth of the skull, were almost identical to the corresponding growth in the control animals. PMID- 8491865 TI - Surgical caution with Carpenter's syndrome. AB - Carpenter's syndrome is a relatively rare craniofacial deformity which will occasionally present to craniofacial surgeons for treatment. Some abnormal anatomical features encountered in two cases which led to unexpected severe intraoperative blood loss are described. PMID- 8491866 TI - Proposal for a modified T-classification for oral cancer. The DOSAK. AB - The UICC plans to publish a modification of the TNM system. A proposal for a T category is calculated out of the data from the DOSAK tumour registry containing more than 3000 cases of primary squamous cell carcinomas of the oral cavity & oropharynx. By adding tumour thickness as a factor of the T component, the prognostic relevance of the classification is enhanced. PMID- 8491867 TI - OKN-related neurons in the rat nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system receive a direct cortical input. AB - It has been previously assumed that the asymmetry of the monocular optokinetic nystagmus (OKN) of lateral-eyed mammals is caused by an absence of visual cortex projections to directional selective neurons in the pretectal nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN). In contrast to this generally accepted hypothesis, we present multiple evidence that OKN-related neurons in the rat NOT-DTN in fact do receive input from the visual cortex. We studied the corticofugal projection to NOT-DTN physiologically, with extracellular single unit recording and electrical stimulation of the optic chiasma and the visual cortex, and anatomically, using retrograde and anterograde tracing techniques. In particular we focussed our attention on the NOT-DTN neurons, which control eye movements during OKN. All OKN-related NOT-DTN cells were activated after optic chiasma stimulation. Forty-five percent of these neurons were also activated after stimulation of the visual cortex (VC). The majority of neurons activated from VC (80%) also responded to monocular stimulation of either eye. On the contrary, most of the neurons that responded to stimulation of the contralateral eye only were not activated from VC. After injection of fluorescent latex microspheres into the NOT-DTN, retrogradely labeled neurons were found in areas 17, 18, and 18A of the visual cortex. Phaseolus vulgaris leucoagglutinin injected into the visual cortex anterogradely labeled fibres and terminals throughout the NOT-DTN complex. Labeled boutons were found in close proximity to OKN-related NOT-DTN cells, selectively stained after horseradish peroxidase (HRP) injections into the inferior olive. Our results demonstrate that NOT-DTN cells in the rat, which are involved in the generation of horizontal OKN, receive a direct input from the ipsilateral visual cortex. PMID- 8491868 TI - Neuronal projections to the medial preoptic area of the sheep, with special reference to monoaminergic afferents: immunohistochemical and retrograde tract tracing studies. AB - The preoptic area contains most of the luteinizing hormone releasing hormone immunoreactive neurons and numerous monoaminergic afferents whose cell origins are unknown in sheep. Using tract tracing methods with a specific retrograde fluorescent tracer, fluorogold, we examined the cells of origin of afferents to the medial preoptic area in sheep. Among the retrogradely labeled neurons, immunohistochemistry for tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase, and serotonin was used to characterize catecholamine and serotonin fluorogold labeled neurons. Most of the afferents came from the ipsilateral side to the injection site. It was observed that the medial preoptic area received major inputs from the diagonal band of Broca, the lateral septum, the thalamic paraventricular nucleus, the lateral hypothalamus, the area dorsolateral to the third ventricle, the perimamillary area, the amygdala, and the ventral part of the hippocampus. Other numerous, scattered, retrogradely labeled neurons were observed in the ventral part of the preoptic area, the vascular organ of the lamina terminalis, the ventromedial part of the hypothalamus, the periventricular area, the area lateral to the interpeduncular nucleus, and the dorsal vagal complex. Noradrenergic afferents came from the complex of the locus coeruleus (A6/A7 groups) and from the ventro-lateral medulla (group A1). However, dopaminergic and adrenergic neuronal groups retrogradely labeled with fluorogold were not observed. Serotoninergic fluorogold labeled neurons belonged to the medial raphe nucleus (B8, B5) and to the serotoninergic group situated lateral to the interpeduncular nucleus (S4). In the light of these anatomical data we hypothesize that these afferents have a role in the regulation of several functions of the preoptic area, particularly those related to reproduction. Accordingly these afferents could be involved in the control of luteinizing hormone releasing hormone (LHRH) pulsatility or of preovulatory LHRH surge. PMID- 8491869 TI - Distribution of glial fibrillary acidic protein-immunopositive structures in the brain of the domestic chicken (Gallus domesticus). AB - The present study is the first comprehensive mapping of glial fibrillary acidic protein (GFAP)-immunopositive structures in the avian brain. Two main types of GFAP-immunopositive elements were observed: (1) nonbranching fibers, occasionally twisted or varicose, and (2) star-shaped cells. Long immunostained fibers originate from the lateral ventricle to form three bundles. Fibers of the dorsal group, emanating from the dorsal/lateral corner of the ventricle, course in lateral, anterior, and ventral directions forming a semidome, which separates the outer pallial (lateral cortical) regions from the underlying striatal mass. The middle group of fibers is directed anteriorly and laterally corresponding to the laminae frontales superior and suprema. The ventral fiber bundle is conical and traverses the lobus parolfactorius, crossing also the lamina medullaris dorsalis (the latter consisting mainly of star-shaped cells). The hippocampus, septum, and hypothalamus also contain straight radial fibers. In some areas, given their variable orientation, the fibers cannot be regarded as merely persisting radial glia. In the telencephalon, the nuclei basalis, accumbens, ectostriatum, paleostriatum primitivum, and the ventral paleostriatum are particularly rich in GFAP-positive cells, whereas the neostriatum, hyperstriatum, and paleostriatum augmentatum are almost devoid of GFAP labelling. Certain nuclei of the thalamus and the lower brainstem are conspicuous by their low levels of GFAP immunoreactivity. The Bergmann glia were GFAP-immunonegative. PMID- 8491870 TI - Topography of projections to the frontal lobe from the macaque frontal eye fields. AB - Efferents from the frontal eye fields (FEF) to the ipsilateral frontal lobe were studied by autoradiography of tritiated tracers (leucine, proline, and fucose) in seven macaque monkeys that were used previously to describe subcortical connections. In four of the cases, tracer injection sites were confirmed by low thresholds for the electrical elicitation of saccadic eye movements. Cases were grouped as lFEF of sFEF cases according to large or small saccades that were characteristic of the injection site. Projections from the FEF terminated in five frontal regions: 1) area FD on the dorsomedial convexity; 2) area FC (containing SEF) medial to the upper limb of the arcuate sulcus; 3) areas FD and FD delta along the walls of the principal sulcus; 4) area FCBm on the deep, posterior wall of the arcuate sulcus inferior to the sulcal spur; and 5) the inferolateral cortex (area FDi) on the convexity and lateral two thirds of the anterior wall of the arcuate sulcus. Projections in sFEF cases tended to be confined to medial parts of dorsomedial FD and FC and the lateral wall of the principal sulcus and inferolateral convexity. Neither lFEF nor sFEF appeared to project to the SMA or pericingulate cortex. Label in these areas was found only in the cases in which tracer spread into non-FEF areas. FEF projections terminated in column-like patches of about 500-600 microns in diameter. Labeled axons and terminals were seen in all cortical layers regardless of location in the frontal lobe. PMID- 8491871 TI - Skin manifestations of cardio-facio-cutaneous syndrome. AB - The recently described cardio-facio-cutaneous syndrome is within the spectrum of multiple congenital anomalies-mental retardation syndromes. We describe two additional cases and review 22 previously reported cases. Our two patients had many of the cardinal features of the disorder: a peculiar craniofacial appearance with sparse curly hair, low-set posteriorly rotated ears, moderate to severe mental retardation, heart defects, and cutaneous abnormalities such as ichthyosis, widespread keratosis pilaris, keratosis pilaris atrophicans faciei, and palmoplantar keratoderma. PMID- 8491872 TI - Trichothiodystrophy associated with photosensitivity, gonadal failure, and striking osteosclerosis. AB - Three new unrelated cases of PIBIDS (Photosensitivity, Ichthyosis, Brittle, sulfur-deficient hair [trichothiodystrophy], Impaired intelligence, Decreased fertility, and Short stature) are reported. Decreased survival of skin fibroblast lines after UVB exposure was found. All three male patients had hypogonadism and primary end-organ gonadal failure. Striking osteosclerosis was present in all three patients. To the best of our knowledge the third patient is the first reported case of a black man with PIBIDS. PMID- 8491873 TI - Allergic contact dermatitis from color film developers: clinical and histologic features. AB - We evaluated two patients with allergic contact dermatitis that resulted from exposure to color film developers. A lichenoid eruption developed in one patient, whereas an eruption more characteristic of an acute spongiotic dermatitis developed in the second patient. Histologic findings in the first case were those of a "lichenoid dermatitis" but with features distinct from classic lichen planus. The biopsy specimens from the second patient showed a subacute spongiotic process with a bandlike infiltrate suggestive of an evolving lichenoid process. Contact allergy to color developers may result in eruptions similar to lichen planus. This process appears to evolve from an acute spongiotic dermatitis in its early phase to a lichenoid dermatitis in fully developed and more chronic forms. Although the histologic features are those of a "lichenoid" dermatitis, some features, such as the presence of spongiosis, eosinophils, and a less intense inflammatory infiltrate, may enable distinction between lichenoid allergic contact dermatitis and true lichen planus. In addition, clinicopathologic correlation with patch test results should permit accurate diagnosis in most cases. PMID- 8491874 TI - Ischemic venous thrombosis caused by a distinct disturbance of the extrinsic clotting system. AB - Ischemic venous thrombosis that led to necrosis of four toes developed in an 81 year-old man. Despite the extensive thrombosis, results of blood clotting tests showed an extremely low prothrombin time (20%). Plasma mixing studies demonstrated an inhibitor that may have features in common with the lupus anticoagulant. Lupus anticoagulant also simulates hemorrhagic diathesis in vitro, whereas in vivo it is associated with thrombosis and thromboembolism. In contrast to the lupus anticoagulant, the inhibitor found in this patient was active within the extrinsic clotting system. Systemic steroids led to rapid clinical resolution paralleled by normalization of the prothrombin time and disappearance of the inhibitor. PMID- 8491875 TI - Bilateral vulvar basal cell carcinomata. AB - Vulvar basal cell carcinoma is rare, accounting for less than 5% of vulvar neoplasms. There is great variation in the clinical appearance of this neoplasm, which occurs most commonly in older women. Metastasis seldom occurs, but the tumor may extend deeply into local tissues. We report the first case of bilateral vulvar basal cell carcinomata in a 66-year-old woman who had received radiotherapy for urethral carcinoma 35 years earlier. Both tumors were treated with Mohs micrographic surgery and have not recurred after 13 years. PMID- 8491876 TI - Focal dermal hypoplasia: four cases with widely varying presentations. AB - We describe four patients with focal dermal hypoplasia (FDH): a girl with classic FDH, a boy with cutaneous findings, an infant with severe multisystem disease, and the infant's mother, who had previously undiagnosed FDH. These patients illustrate the classic cutaneous manifestations of FDH and the variations that can exist within a family. PMID- 8491877 TI - Acquired cutaneous smooth muscle hamartoma. AB - A 35-year-old white man had an indurated, indistinct plaque on the anterior aspect of the neck for 10 years. Results of biopsy specimens showed an excess of smooth muscle bundles scattered throughout the dermis. Unlike previously reported cases of acquired smooth muscle hamartomas, it did not occur in association with a Becker nevus. PMID- 8491878 TI - Erythema elevatum diutinum associated with Wegener's granulomatosis and IgA paraproteinemia. AB - A 69-year-old man had erythema elevatum diutinum for several years before he developed IgA paraproteinemia and a limited form of Wegener's granulomatosis. This is the first report of an association between erythema elevatum diutinum and Wegener's granulomatosis. IgA paraproteinemia has been reported in association with erythema elevatum diutinum but not with Wegener's granulomatosis. PMID- 8491879 TI - Cryoglobulinemia and cutaneous leukocytoclastic vasculitis associated with hepatitis C virus infection. AB - Hepatitis C virus infection is a frequent cause of non-A, non-B hepatitis worldwide. Resultant morbidity is significant; chronic liver disease develops in 50% of infected persons. Since serologic testing has become available there have been several reports of cutaneous findings in association with hepatitis C virus infection, including vasculitis, cryoglobulinemia, urticaria, and lichen planus. We describe a patient with cryoglobulinemia, chronic cutaneous leukocytoclastic vasculitis, and hepatitis C virus infection. Hepatitis C virus infection should be included in the differential diagnosis of the causes of cryoglobulinemia and leukocytoclastic vasculitis. PMID- 8491880 TI - Retinoid hepatitis. AB - A 65-year-old woman treated with etretinate for pityriasis rubra pilaris developed chronic active hepatitis. The elevated transaminases were noted 2 months after initiation of therapy and peaked 2 months after discontinuation of etretinate. The spectrum of liver toxicity induced by etretinate is reviewed. We suggest that reported cases of retinoid-induced liver disease can be divided into four distinct categories: nonspecific reactive hepatitis, acute hepatitis, chronic active hepatitis, and severe fibrosis or cirrhosis. PMID- 8491881 TI - Three neonatal cases of epidermolysis bullosa herpetiformis (Dowling-Meara type) with severe erosive skin lesions. AB - We describe three neonates who had large eroded areas of skin on their extremities. The clinical course and ultrastructural findings were consistent with a diagnosis of epidermolysis bullosa herpetiformis (Dowling-Meara type). In each case blisters developed around eroded areas after birth and enlarged centrifugally in a herpetiform fashion. One patient died of sepsis at 8 days of age. In the two survivors blister formation subsided gradually within 1 year. Ultrastructural studies confirmed intraepidermal blister formation associated with spheric aggregates of tonofilaments in the lower epidermis. Spheric aggregates were also found in clinically uninvolved skin. PMID- 8491882 TI - Posttransfusion graft-versus-host disease in two immunocompetent patients. AB - Graft-versus-host disease may occur in certain immunocompromised patients after a blood transfusion. The disease is characterized by fever, a skin eruption, gastrointestinal disturbances, liver dysfunction, and bone marrow aplasia. Two cases of fatal graft-versus-host disease are reported. Both patients were immunocompetent and had received transfusions of nonirradiated blood from their children during surgery. The importance of preventing this complication by irradiating blood products given to patients by their first-degree relatives is underscored. PMID- 8491883 TI - Peculiar facial erythematosquamous lesions in two siblings with cyclical summer improvement and winter relapse: a variant of keratosis lichenoides chronica? AB - A 7-year-old girl had erythematous hyperkeratotic papules and plaques that improved in summer and recurred in winter since the age of 4 months. She had had irregular, ridge-like erythematosquamous lesions on the arms with the same seasonal variation. The lesions on the arms improved with age. Light and electron microscopic examination showed marked degeneration of keratinocytes and prominent apoptosis. Her older brother had a similar but milder dermatosis. We believe these cases may represent a variant of keratosis lichenoides chronica. PMID- 8491884 TI - Zirconium granuloma resulting from an aluminum zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. AB - Zirconium compounds have been associated with the development of hypersensitivity granulomas. However, aluminum zirconium complexes have not previously been shown to induce sensitization. We present the clinical and histologic findings of a case in which a patient developed an acute hypersensitivity reaction to an aluminum zirconium complex. PMID- 8491885 TI - Pemphigus vulgaris and pregnancy: risk factors and recommendations. AB - Pemphigus vulgaris during pregnancy is exceedingly rare; only 15 cases with immunopathologic confirmation have been reported. In the four cases associated with fetal mortality the mother's disease was active and required high doses of corticosteroids and adjuvant therapy with azathioprine or dapsone for control. A pregnant woman with limited disease is described. At the time of delivery her pemphigus vulgaris antibody titer was 1:640. A full-term, healthy male infant was completely free of skin lesions after a spontaneous vaginal delivery. PMID- 8491886 TI - Sporotrichosis presenting as arthritis and subcutaneous nodules. AB - Arthritis is a rare manifestation of systemic sporotrichosis. A patient who had sporotrichal arthritis of both wrists and elbows is described. Predisposing factors included alcoholism, rose gardening, and antecedent trauma. The onset of the arthritis was insidious, and the diagnosis was made 2 1/2 years after his first symptoms were noted. Treatment with surgical debridement and a 23-week course of ketoconazole was unsuccessful. A review of the literature suggests that some combination of intravenous or intraarticular amphotericin B and potassium iodide, ketoconazole, or surgery is necessary for effective treatment. PMID- 8491887 TI - Acute monoblastic leukemia with skin nodules in an adult. AB - An 18-year-old man had a 3-week history of malaise, a 1-week history of a papular eruption, and increasingly severe multisystem neurologic symptoms. A diagnosis of acute monoblastic leukemia was made. Immunophenotypic characterization of peripheral blood, bone marrow, and cutaneous infiltrates revealed a predominant myelomonocytic phenotype with the coexpression of intercellular adhesion molecule type 1, IgE receptor, terminal deoxynucleotidyl transferase, and some T-cell markers. These findings may have important clinical and pathogenetic implications regarding the biologic and pathologic behavior of the myelomonocytic leukemic cells. They also explain in part the impressive presentation of the disease in the skin. PMID- 8491888 TI - Unilateral linear lichenoid eruption after bone marrow transplantation: an unmasking of tolerance to an abnormal keratinocyte clone? AB - Chronic cutaneous graft-versus-host disease may appear clinically as a lichenoid eruption. We describe a 26-year-old man who developed a unilateral linear lichenoid eruption 7 months after allogeneic bone marrow transplantation. We believe this represents an unusual form of localized, chronic graft-versus-host disease. The possible relationship to viral infection or cellular mosaicism and the clinical, histologic, and immunologic similarities to idiopathic lichen planus are discussed. PMID- 8491889 TI - Pigmentary lines of the newborn. AB - We report three cases of infants born with extensive linear and retiform pigmentation on the trunk and extremities. In none of these cases was there an associated underlying medical disorder, and in all cases the pigmentation resolved by 6 months of age. It appears that the treatment of choice for this transient disorder is reassurance. PMID- 8491890 TI - Amelanotic metastatic melanoma in a patient with oculocutaneous albinism. AB - Melanomas are rare in patients who have albinism, compared with the frequent occurrence of squamous cell carcinomas and basal cell carcinomas. This report describes amelanotic metastatic melanoma in a 58-year-old Japanese man who had tyrosinase-positive oculocutaneous albinism. A prolonged bleeding time, facioscapulohumeral muscular dystrophy, and Gilbert syndrome were also present. Superficial spreading melanoma with evidence of spontaneous regression on his right forearm was suspected as a possible primary site. Twenty-two cases of melanomas in persons who have albinism have been reported. PMID- 8491891 TI - Role of CT in chronic pulmonary embolism: comparison with pulmonary angiography. AB - To assess the value of CT in chronic pulmonary embolism (CPE), CT scans and pulmonary angiograms of 21 consecutive patients were reviewed. Computed tomography was better than angiography in assessing proximal clots (three thrombi not seen by angiography, three angiographic false-positives confirmed by surgery). Furthermore, CT was able to analyze pulmonary arteries distal to angiographic amputations. Computed tomography was less sensitive than angiography for vascular distortions (38 vs. 50%) and stenosis (35 vs. 71.8%). Pulmonary infarctions were better detected and characterized by CT than by angiography. Isolated parenchymal ground-glass opacities were seen by CT in 18 patients, especially in those with right cardiomegaly. High resolution CT delineated them better than did standard CT. Computed tomography may be a useful adjunct to angiography in the assessment of CPE. PMID- 8491892 TI - CT findings in bronchiolitis obliterans organizing pneumonia (BOOP) with radiographic, clinical, and histologic correlation. AB - The CT features of 12 patients with bronchiolitis obliterans organizing pneumonia (BOOP) were reviewed and correlated with clinical history, histologic specimens, and chest radiography. From our series, a spectrum of CT findings of parenchymal lung involvement in BOOP emerged. Focal nodular or mass-like opacities were found in 42% (5 of 12). Areas of consolidation resembling pneumonia were seen in 33% (4 of 12). Peripheral subpleural reticular opacities were identified in 25% (3 of 12). Patchy ground glass infiltrates were seen in 8% (1 of 12). One patient demonstrated a mixed pattern consisting of nodular opacities and areas of pneumonic consolidation. In 4 of the 5 cases demonstrating the nodular form of BOOP either a feeding vessel or bronchus sign could be identified. This feature consisted of a pulmonary vessel leading to a nodular opacity or an air bronchogram entering into a nodular opacity. Correlation of the CT findings of BOOP with histologic specimens showed nodular opacities and areas of consolidation to be associated with classic pathologic features of BOOP including bronchiolar plugs of granulation tissue and surrounding organizing pneumonia. Cases demonstrating peripheral subpleural reticular opacities showed, in addition to pathologic evidence of BOOP, other features such as interstitial disease and fibrosis. PMID- 8491893 TI - Rib counting on CT using the sternal approach. AB - To devise a new method for counting ribs on CT scan, we evaluated the CT anatomy of the costal cartilages and the proximal xiphoid in 20 control patients without rib pathology. The sternal end of costal cartilages seen on the same image as the proximal xiphoid was always the seventh (n = 20). These costal cartilages were located anterolateral (n = 13) or lateral (n = 7) to the proximal xiphoid. In fifteen patients with rib pathology, 23 abnormal ribs were localized by our method. All of these ribs correlated with those seen on chest radiographs and rib cage views or with resected ribs on postoperative films. PMID- 8491894 TI - Tuberculosis of the ribs: CT appearance. AB - Tuberculosis is the most common inflammatory lesion of the ribs, second only to metastatic neoplasm as a destructive cause of a rib lesion. We retrospectively analyzed CT findings of 13 lesions in eight patients with pathologically proven rib tuberculosis. The presenting symptoms were painful mass in five, chest pain in two, and nontender mass in one. Five patients had concomitant pulmonary tuberculosis. On CT, all showed a juxtacostal soft tissue mass with central low attenuation and peripheral rim enhancement (a so called "cold abscess"). Only 4 of 13 lesions demonstrated bone destruction: two were osteolytic expansile lesions with cortical disruption and two were mild cortical irregularities. Five lesions were located at the costochondral junction, five were in the rib shaft, two were in the sternochondral junction, and one was in the costovertebral joint. There was no evidence of direct extension into the lung parenchyma. PMID- 8491895 TI - CT assessment of resectability prior to transhiatal esophagectomy for esophageal/gastroesophageal junction carcinoma. AB - The ability of preoperative CT to assess resectability and to stage carcinoma of the esophagus and gastroesophageal junction was studied in 71 patients who underwent transhiatal esophagectomy. Patients with preoperatively proven distant metastases who did not have surgery were not included in the present study. At surgery the tumor invaded adjacent mediastinal or abdominal structures in 18 patients (prevalence 25%), but was nonresectable in only 7 of these 18 patients (39%). Invasions of the tracheobronchial tree, the aorta, and the diaphragm were correctly detected on CT in 5 of 6, 1 of 2, and 2 of 10 patients. There were four false-positive results on CT; tracheobronchial invasion and pericardial invasion were incorrectly predicted in one and three patients, respectively. Invasion of adjacent structures was correctly assessed on CT in 58 (82%) patients and the depth of tumor invasion was correctly determined in 49 (69%) patients. Computed tomography correctly staged 57% of patients according to the classification of the American Joint Committee on Cancer. Understaging (31%) occurred more often than overstaging (11%). In the present study, computed tomography was not effective in assessing non-resectability by diagnosing invasion because of the relatively low prevalence of invasion of adjacent structures and the fact that invasion was often not associated with nonresectability. In assessing invasion itself, CT was accurate in diagnosing tracheobronchial involvement, but was limited in diagnosing invasion of other adjacent structures. In assessing stage grouping, CT was limited in detecting either diaphragmatic invasion or lymph node involvement. PMID- 8491896 TI - CT of calcified chronic aortic dissection simulating atherosclerotic aneurysm. AB - Calcification along the outermost aspect of the aorta usually means atherosclerotic aneurysm. On occasion, however, this peripheral type calcification is seen in chronic aortic dissection and leads to a misdiagnosis. Conventional chest roentgenography and CT of 50 cases of chronic dissection proven by angiography were reviewed. Four of these cases (8%) showed calcification in the outermost wall of the affected portion of the aorta. Two cases were Stanford type A and the other two cases were type B. In type A cases chest roentgenography showed calcification in the wall of the dilated ascending aorta closely mimicking aneurysm. In type B cases, calcification was in the outer wall of a localized hump in the descending aorta. Computed tomography clearly demonstrated that this peripheral calcification was located in the outermost wall of the false lumen. Review of the pathologic literature shows sporadic reports of such phenomenon and a theory of endothelialization of the false lumen. It is presumed that the endothelialized false lumen may develop atheromatous changes much more rapidly than the true lumen since two of four cases showed calcification only in the wall of the false lumen with the intimal flap and the wall of the true lumen remaining noncalcified. PMID- 8491897 TI - Left-sided omental infarction with associated omental abscess: CT diagnosis. AB - The CT findings of two patients with left-sided omental infarction associated with acute inflammation and abscess formation are described and illustrated. The patients presented with lower abdominal pain, fever, and leukocytosis, and they exhibited a poorly defined heterogeneous low-attenuated mass containing fat in the anterior left lower abdomen. Although segmental omental infarction is usually a self-limiting condition that may resolve spontaneously, necrosis associated with secondary infection and abscess formation may develop occasionally. PMID- 8491898 TI - Intestinal infarction secondary to mesenteric venous thrombosis: CT-pathologic correlation. AB - We reviewed CT of four patients with surgically proved bowel infarction secondary to superior mesenteric vein (SMV) thrombosis. Pathologic correlation was available in all patients. Three patients had thrombus in both portal vein and proximal SMV and the remaining patient had thrombus that was seen only in the peripheral branches of the SMV. Contrast-enhanced CT showed a segmental distribution of marked concentric bowel wall thickening in all four patients. Two patients also showed zones of different attenuation in the bowel wall, which were caused by varying degrees of edema and hemorrhage in the submucosa. Dense peripheral enhancement of the bowel wall was present in one patient. Other CT findings included ascites and mesenteric changes such as edema and vascular engorgement. The combination of thrombus in the SMV with bowel wall thickening strongly suggests bowel infarction and, therefore, warrants initiation of appropriate therapy. PMID- 8491899 TI - CT analysis of intestinal obstruction due to adhesions: early detection of strangulation. AB - We evaluated the CT of intestinal obstruction due to adhesions in 20 postoperative patients, with emphasis on early detection of strangulation. Ten patients with surgically proven strangulated obstruction (strangulation group) were compared with another ten patients (nonstrangulation group) in whom seven improved with conservative management and three had confirmed simple obstruction on surgical exploration. Beak-like luminal narrowing ("beak") was the most common CT finding at the obstructed site in both groups. The CT findings that suggested strangulated obstruction were serrated beaks, mesenteric edema or vascular engorgement, and moderate to severe bowel wall thickening. In contrast, simple obstruction could be assumed when the beak was smooth, there were no mesenteric changes, and the bowel wall was normal or mildly thickened. Computed tomography is a useful tool for detecting strangulation in patients with postoperative adhesive intestinal obstruction. PMID- 8491900 TI - Pancreatic beta-cell tumors: MRI. AB - Ten consecutive patients with surgically proven beta-islet cell tumors, strongly suspected clinically because of positive laboratory findings, were studied by MRI at 0.5 T. Results were correlated with CT and angiography. MRI detected all 10 insulinomas, with the location confirmed at surgery. Lesion size was < 1 cm in three cases, between 1 and 2 cm in five cases, and between 2 and 3 cm in two cases. A false-negative diagnosis was obtained with CT in 6 of 10 and with angiography in 3 of 10 cases. Our results suggest that if motion artifact can be controlled or reduced, MRI can be employed to localize insulinomas in patients with positive clinical and laboratory findings. PMID- 8491901 TI - CT of primary bilateral adrenal lymphoma. AB - Two cases of bilateral primary adrenal lymphoma are presented. One case had a cystic appearance and the other a homogeneous density. PMID- 8491902 TI - Comparison of MRI with postcontrast CT for the evaluation of acute abdominal trauma. AB - We compared the ability of MRI and CT to detect and characterize abdominal visceral injury. Seven patients with contrast-enhanced abdominal CT interpreted as showing definite (five patients) or possible (two) solid organ injury following blunt abdominal trauma were referred for abdominal MRI with a mean interval of 3 days between modalities. T1-weighted and T2-weighted spin echo sequences were obtained in all patients. Gradient-recalled echo (GRE) sequences (22-25/12-13/60 degrees flip angle) were obtained in five cases. Both CT and MR allowed detection of complex splenic lacerations in two patients and complex hepatic injuries in three other patients. A sixth patient had subtle periportal hypodensity noted on CT which was not detected prospectively on MRI. One patient had a right adrenal hematoma detected on MRI but not on CT. Relative lesion conspicuity and extent were judged equal on CT and T2-weighted imaging. The T1 weighted and GRE imaging were judged inferior to CT. We conclude that MRI offers no significant advantage over CT for the routine evaluation of acute abdominal trauma. PMID- 8491903 TI - MRI of extraskeletal osteosarcoma. AB - We report four cases of extraskeletal osteosarcoma of the thigh to illustrate MRI findings of this rare neoplasm. Calcifications or osteoid material were not discernible in these tumors on MRI or conventional radiography. Three tumors were well demarcated on MRI and corresponded to pseudoencapsulation on radiologic pathologic correlation. These three tumors were heterogeneous in appearance and were hyperintense to muscle on T1-weighted imaging and demonstrated high signal intensity on T2-weighted imaging. In the fourth tumor, which occupied almost the entire thigh, MRI before and after intravenous gadopentetate dimeglumine administration revealed cystic, hemorrhagic, and solid components. Pathological examination revealed a cystic hemorrhagic cavity containing necrotic and viable tumor and a large solid tumor component. The MRI findings in extraskeletal osteosarcoma are non-specific. However, in the appropriate age group the differential diagnosis of a soft-tissue mass in the thigh should include extraskeletal osteosarcoma, even in the absence of radiographically discernible calcifications or osteoid material within the soft-tissue mass. PMID- 8491904 TI - MRI of soft-tissue lesions: opposed-phase T2*-weighted gradient-echo images. AB - We evaluated the ability of opposed-phase T2*-weighted gradient-echo (T2*GE) MRI to demarcate soft tissue lesions. The series contained 37 cases, including 18 benign tumors, 8 malignant tumors, and 11 miscellaneous nonneoplastic soft-tissue lesions. Images were obtained on a 0.5 T magnet with T2*GE imaging (TR/TE 300/22 ms, 20 degrees). Results were compared with those of T1-weighted SE images (500/20-40) and T2-weighted SE (T2SE) images (2,000/80). The T2*GE images were similar to T2SE images with respect to the signal behavior and internal architecture of the masses in many cases. In some instances, they were better than T2SE images in delineating the lesions and adjacent fat tissue, in delineating the lesions and adjacent small vessels, and in depicting special features such as hemosiderin deposits. They were inferior to T2SE images in delineating the lesions and adjacent muscles. Because of reduced lesion-muscle delineation, T2*GE images can not be substituted for T2SE images in the evaluation of soft-tissue lesions, but are useful as an adjunct in some cases. PMID- 8491905 TI - Fast spin-echo imaging of intracranial neoplasms. AB - Our goal was to compare dual echo fast SE (FSE) T2-weighted MRI of intracranial neoplasms with conventional SE (CSE) images. In phase 1 of the study, CSE and FSE dual echo MR studies of 33 patients with intracranial neoplasms and 26 normal controls were separately interpreted by three neuroradiologists blinded to clinical history to ascertain differences in lesion conspicuity. The CSE and FSE images were read independently, in random order, with at least a 3 week interval between readings. In phase 2 of the study, CSE and FSE sequences were compared side by side by three neuroradiologists independently to evaluate lesion conspicuity and artifacts and to determine whether FSE would be an acceptable replacement for CSE imaging. Lesion detection was equivalent in 111 of 117 interpretations (94.9%). The CSE and FSE sequences were equivalent in detecting lesion-associated abnormalities (hemorrhage, calcium, mass effect, edema, and hydrocephalus) and in characterizing lesion size, margins, and signal intensity. Nonspecific T2 white matter hyperintensities were detected more often with CSE, while susceptibility artifacts were less conspicuous on FSE. Ventricular catheters, postoperative soft tissue and bony changes, and postradiation therapy changes were detected equally well on both sequences. In phase 2 of the study, lesion conspicuity and presence of artifacts were felt to be equivalent with the two sequences. The FSE sequences can serve as a rapid, feasible alternative to conventional CSE sequences for intracranial tumor detection. PMID- 8491906 TI - Pituitary metastases: MR findings. AB - Tumors metastatic to the pituitary gland are uncommon, and they are difficult to differentiate radiologically from pituitary adenomas. We retrospectively reviewed the MR examinations and clinical records of nine patients with radiographic and/or clinical evidence of pituitary metastases. The most common clinical symptoms included cranial nerve deficits (67%) and/or pituitary dysfunction (30%). Both occurred acutely and progressed rapidly over 1-4 weeks in all patients. Cranial nerve involvement was predominantly multiple (83%), a reflection of involvement of the adjacent cavernous sinus. In contrast to previous reports indicating a predilection for symptoms related to posterior lobe involvement (71%), our study shows that symptoms related to the anterior lobe are as common as posterior lobe symptoms. Useful MR findings included a relatively small, enhancing pituitary lesion (< or = 1.5 cm in 56%) that was relatively isointense to brain on both T1- and T2-weighted images (78%) and involvement of the hypothalamus/pituitary infundibulum (44%) or cavernous sinus (56%). PMID- 8491907 TI - CNS cryptococcosis in AIDS: spectrum of MR findings. AB - Cryptococcus is a ubiquitous saprophytic fungus that may become pathogenic, particularly in immunosuppressed patients. In the CNS of AIDS patients, the incidence of this fungal infection is 5% of all the opportunistic infections. In this study, we review the MR findings in nine AIDS patients affected by CNS cryptococcosis. All MR studies were performed before and after intravenous administration of a single dose of gadopentetate dimeglumine and again after an additional dose. Autopsy was performed in one case. Magnetic resonance imaging revealed evidence of meningitis or meningoencephalitis, dilated Virchow-Robin spaces, cyst-like structures (gelatinous pseudocysts), and granulomas (cryptococcomas) of the choroid plexuses. The last two findings (pseudocysts and choroidal ependymal granulomas) are relatively specific for cryptococcosis. PMID- 8491908 TI - 3D MPRAGE evaluation of the internal auditory canals. AB - A heavily T1-weighted three-dimensional (3D) gradient echo sequence utilizing a 180 degrees inversion pulse has become available for clinical use, called magnetization prepared rapid acquisition gradient echo (MPRAGE). With the appropriate choice of repetition time, echo time, flip angle, and inversion time (TI), T1-weighted imaging can be performed with excellent anatomic detail and a good signal-to-noise ratio. We performed an initial evaluation of this sequence for detection of abnormalities of the internal auditory canals compared with conventional spin echo (SE) imaging. Fifteen men and 15 women were evaluated. Diagnoses included normal (n = 15 patients), acoustic neuromas (n = 7 tumors in 4 patients), cerebellopontine angle meningiomas (n = 3), postoperative for acoustic neuroma without residual tumor (n = 2), postoperative with evidence of residual tumor (n = 3), glomus jugulare (n = 1), Bell palsy (n = 1), and vestibular enhancement of probable viral etiology (n = 1). The 3D MPRAGE study consisted of 128 coronal partitions, (10/4/1), 10 degrees flip angle, 130 x 256 matrix, 2 mm slice thickness. TI time of 350 ms, 1 s recovery time, and 5.43 min examination time. All enhancing lesions identified on the conventional SE T1-weighted imaging were also identified on the MPRAGE imaging. No diagnostic difference existed between the MPRAGE and conventional SE sequences when pathology was present, but the MPRAGE sequence did have poorer resolution in the axial reformats related to the 130 x 256 in-plane matrix. While not currently able to replace conventional two-dimensional SE imaging, 3D MPRAGE may provide a valuable adjunct to the routine imaging protocol. This technique could replace the coronal T1-weighted SE sequence and provide excellent gray-white differentiation and many contiguous thin sections without a great increase in overall examination time. PMID- 8491909 TI - Spinal neurilemmomas and neurofibromas: central dot sign in postgadolinium MRI. AB - The MR studies of three histologically proven spinal neurilemmomas and neurofibromas were reviewed retrospectively. There were two benign neurilemmomas (schwannomas) and one neurofibroma. The common characteristic of these cases was a central low intensity focus ("dot") seen on postcontrast T1-weighted imaging. The low intensity foci corresponded histologically to a congeries of changes including edema, microcysts, foam cells, hyalinization of blood vessels, old hemorrhage, and dystrophic calcification. PMID- 8491910 TI - MR evaluation of the temporomandibular joint in juvenile rheumatoid arthritis. AB - Temporomandibular joint (TMJ) disease is uncommon in children but frequently occurs in juvenile rheumatoid arthritis (JRA). Involvement is often asymptomatic; however, it can lead to growth disturbances and facial deformity. Thirty TMJs in 15 children (11 girls and 4 boys aged 3.5-18 years) with JRA were evaluated clinically and by MRI. Plain films were reviewed when available. Magnetic resonance imaging parameters included T1-weighted and in some cases T2-weighted or gradient recall echo sequences. We assessed condylar configuration, glenoid fossa changes, presence of erosions, disk abnormality, range of motion, and presence of joint effusions or pannus. Abnormalities included cortical erosions (n = 19), disk thinning (n = 18), and perforation (n = 2). Reduction of joint movement (n = 20), joint locking (n = 3), and pannus/effusions (n = 5) were also found. Magnetic resonance imaging is a useful technique for the detection of TMJ involvement in JRA. Early detection and therapeutic intervention may lessen or prevent subsequent deformities. PMID- 8491911 TI - Neural network mapping for nonlinear stereotactic normalization of brain MR images. AB - We present techniques of automatic nonlinear transformation of MR images (2D or 3D). A neural network automatically finds the corresponding parts between the subject's brain images and the standard images. By iterative operations, the network generates a set of image-shifting vectors to realize a plastic transformation. For precise matching, a set of markers can be placed manually before starting the transformation on landmarks of the images, e.g., on the anterior-posterior commissural line and on the central sulcus. PMID- 8491912 TI - Graphical analysis of MR feature space for measurement of CSF, gray-matter, and white-matter volumes. AB - The problem of volume averaging in quantitating CSF, gray-matter, and white matter fractions in the brain is solved using a three-compartment model and a simple graphical analysis of a multispectral MR feature space. Compartmentalization is achieved without the ambiguities of thresholding techniques or the need to assume that the underlying pixel probability distributions have a particular form. A 2D feature space is formed by double SE (proton density- and T2-weighted) MR data with image nonuniformity removed by a novel technique in which the brain itself serves as a uniformity reference. Compartments other than the basic three were rejected by the tailoring of limits in feature space. Phantom scans substantiate this approach, and the importance of the careful selection and standardization of pure tissue reference signals is demonstrated. Compartmental profiles from standardized subvolumes of three normal brains, based on a 3D (Talairach) coordinate system, demonstrate slice-by-slice detail; longitudinal studies confirm reproducibility. Compartmentalization may be described graphically and algebraically, complementing data displays in feature space and images of compartmentalized brain scans. These studies anticipate the application of our compartmentalization technique to patients with neurological disorders. PMID- 8491913 TI - Metastatic pulmonary calcification: early detection by high-resolution CT. AB - A 41-year-old man with a renal transplant was admitted with cough, fever, and dyspnea. Although chest radiography was normal, high-resolution CT demonstrated small hazy round opacities in the centrilobular regions throughout both lungs. The biopsy specimen revealed metastatic calcification in the alveolar septa and the walls of the bronchioles and arterioles. High-resolution CT may be useful for the early detection of metastatic pulmonary calcification when plain radiography is negative and therapy has the potential to reverse the process. PMID- 8491914 TI - Shwachman syndrome: CT and MR diagnosis. AB - The MR and CT features of the pancreas are described in an 18-year-old woman. Lipomatosis of the pancreas found on MR and CT and the clinical findings pancytopenia, short stature, and recurrent infections are typical for Shwachman syndrome. PMID- 8491915 TI - Massive ovarian edema: ultrasound and MR characteristics. AB - Massive ovarian edema (MOE) is a benign enlargement of the ovary caused by edema, which is believed to result from intermittent or partial torsion of the ovarian pedicle. We report a case of MOE in a pregnant patient. PMID- 8491916 TI - Leydig cell tumor of the testis in Klinefelter syndrome: MR detection. AB - Klinefelter syndrome is associated with the development of breast and extragonadal germ cell tumors in some patients. Leydig cell tumor in association with Klinefelter syndrome is a rare entity. We report such a case to illustrate the usefulness of MR imaging in detecting a testicular neoplasm when clinical examination and ultrasonography are equivocal. PMID- 8491917 TI - MR demonstration of a persistent median artery in carpal tunnel syndrome. AB - The median artery of the forearm appears early in embryological development and normally involutes before birth. In rare cases, it persists into adult life. Although usually asymptomatic, it can be a cause for carpal tunnel syndrome (CTS). This report describes the MR appearance of a persistent median artery in a patient with CTS. The symptoms were relieved after resection of the aberrant vessel. PMID- 8491918 TI - Muslin-induced optic arachnoiditis ("gauzoma"): findings on CT and MR. AB - We report a case with a paraophthalmic aneurysm that was wrapped with muslin because it was unclippable. Six months after wrapping, the patient developed gradual vision loss involving the ipsilateral eye. Both CT and MR studies demonstrated a loculated fluid collection with marked surrounding enhancement in the region of the previous surgery. Craniotomy revealed an abscess centered in the region of the aneurysmal wrapping. Pathological diagnosis was consistent with a foreign-body reaction with acute and chronic inflammation. Postoperatively the patient showed improvement in vision. We describe the MR findings in this case of muslin-induced optic arachnoiditis ("gauzoma"). PMID- 8491919 TI - MRI of gangliocytoma of cerebellum and spinal cord. AB - Gangliocytomas are rare CNS tumors that occur in children and young adults. We present a case of a cerebellar gangliocytoma with invasion of the cervical spinal cord demonstrated on MR. Radiographic differentiation of gangliocytomas from other ganglion cell tumors--ganglioglioma, dysplastic gangliocytoma of Lhermitte Duclos, and desmoplastic infantile ganglioglioma--is discussed. PMID- 8491920 TI - Ossifying fibroma of sphenoid bone with coexistent mucocele: CT and MRI. AB - A case of a 26-year-old woman with decreasing vision in her right eye, diplopia, headache, and galactorrhea is presented. Both CT and MR studies showed a large sphenoid fibroosseous lesion that had a ground glass appearance on CT and low-to intermediate proton density and low T2-weighted and low T1-weighted signal intensities on MR. After contrast medium administration, this process diffusely enhanced on CT and MR. There was also an expansile mass in the sphenoid sinus that had intermediate proton density, high T2-weighted and low T1-weighted signal intensities compared with brain. This mass did not enhance but had an intensely enhancing, uniformly thin rim. The pathologic diagnosis was ossifying fibroma with a sphenoid sinus mucocele. There are only isolated reports in the literature of benign fibrosseous lesions causing mucoceles. This association is reviewed as are the findings in this case. PMID- 8491921 TI - Ramsay-Hunt syndrome and high-resolution 3DFT MRI. AB - A case of Ramsay-Hunt syndrome has been studied with pre- and postcontrast MR imaging, using a three-dimensional Fourier transform fast imaging with steady precession sequence with axially oriented sections and coronal reformatted images. A clear demonstration of the abnormal enhancement of the labyrinth and of the intratemporal cranial nerves was obtained. This demonstration assisted us in establishing the diagnosis of Ramsay-Hunt syndrome. PMID- 8491922 TI - Rupture of brain stem abscess into fourth ventricle: MR demonstration. PMID- 8491923 TI - Gastric carcinoma metastases to extraocular muscles. PMID- 8491924 TI - Mesenteric panniculitis: MR findings. PMID- 8491925 TI - Mucinous cystadenoma of the pancreatic tail with ductal communication. PMID- 8491926 TI - Adrenal hemangioma: MR findings with pathologic correlation. PMID- 8491927 TI - Cavernous hemangioma of the adrenal gland: CT appearance. PMID- 8491928 TI - Social goals: relationship to adolescent adjustment and to social problem solving. AB - Examined the relations between adolescent boys' social goals of dominance, revenge, avoidance, and affiliation and (1) self-reported negative adolescent outcomes; (2) subjective sense of self-esteem; and (3) externalizing, internalizing, and prosocial behaviors, as rated by peers and teachers. Results indicated that social goal values were related to diverse aspects of self-, teacher-, and peer-reported social and behavioral functioning, with a consistent association found between a range of delinquent, substance-using, and behavioral difficulties, and endorsement of high goal values for dominance and revenge and low goal values for affiliation. Results also indicated that teacher-identified aggressive boys differed from nonaggressive boys in the value they placed on social goals, with aggressive boys placing a higher value on goals of dominance and revenge, and lower value on goals for affiliation. Finally social goal choice had a clear relation to the social problem-solving differences of aggressive and nonaggressive boys. PMID- 8491929 TI - Anxiety disorders in African-American and white children. AB - There are little available data on African-American children with anxiety disorders. Treatment-seeking African-American (n = 30) and white children (n = 139), with a current DSM-III-R anxiety disorder, were compared on sociodemographic background variables, clinical characteristics, and lifetime rates of specific DSM-III-R anxiety disorders. Overall, results suggested that the anxiety-disordered African-American and white children who sought treatment from an outpatient mental health facility were more similar than different. The two groups did, however, differ somewhat on several variables (trend only), including rates of school refusal, severity of primary anxiety disorder, lifetime prevalence of posttraumatic stress disorder, and total scores on the Fear Survey Schedule for Children-Revised. More specifically, white children were more likely to present with school refusal and higher severity ratings, while African American children were more likely to have a history of posttraumatic stress disorder and score higher on the FSSC-R. The impact of these findings and the need for additional research are discussed. PMID- 8491930 TI - Instrumental and hostile aggression in childhood disruptive behavior disorders. AB - An analogue task of instrumental and hostile aggression during a competitive game was evaluated in a sample of clinically-referred 8- to 12-year-old aggressive boys. Similar to a prior task in a normative sample (Hoving, Wallace, & La Forme, 1979), both types of aggression increased during provocation as compared to baseline, indicating the success of the provocation manipulation, with moderate correlations between the two aggressive responses. The aggressive group with attention-deficit hyperactivity disorder (ADHD) and the aggressive group without ADHD each had higher rates of instrumental aggression than controls. Only the aggressive/ADHD group had higher rates of hostile aggression than controls. Parent Child Behavior Checklist ratings indicated a modest but significant unique relationship between instrumental aggression and delinquency. The high rate of both types of aggression in the aggressive/ADHD group suggests that comorbid ADHD and aggression may result in qualitative differences in aggressive behavior. The high rate of hostile aggression in the aggressive-ADHD group supports theoretical assumptions regarding the relationship of hostile aggression to poor impulse control. PMID- 8491931 TI - The impact of young children with externalizing behaviors on their families. AB - Compared the impact on families of young children with externalizing behaviors (e.g., hyperactive, aggressive; n = 22), autism (n = 20), or no significant problem behaviors (n = 22) on several measures of family functioning. Previous studies have found heightened stress and parental maladjustment in families with externalizing children. The present study expanded upon that literature by (1) including a clinical control group to determine the specific impact of externalizing problems, (2) focusing on preschool aged children, and (3) using a new measure to directly ascertain parents' perception of impact. Compared to parents with normally developing children, parents with externalizing children reported more negative impact on social life, more negative and less positive feelings about parenting, and higher child-related stress. Moreover, parents of externalizing children reported levels of impact and stress as high as those reported by parents of children with autism. On broader measures of parental and marital well-being, however, the three groups of families of preschoolers did not differ. The implications of these findings for intervention are discussed. PMID- 8491932 TI - Attribution processes in mother-adolescent conflict. AB - Attributions reported by 115 mothers and 122 adolescents were examined as they related to family conflict. Subjects completed measures of parent-adolescent conflict (Issues Checklist, Conflict Behavior Questionnaire) and the Mother Adolescent Attribution Questionnaire. The results revealed that parent-adolescent conflict correlated with mothers' and teenagers' negative attributions. Specifically, self-reported conflict was positively correlated with mothers' and teenagers' beliefs that one another's negative behavior was intentional, selfishly motivated, and blameworthy. PMID- 8491933 TI - Homemaker role experiences affect toddler behaviors via maternal well-being and parenting behavior. AB - A model delineating the relationship between homemakers' role experiences and toddler behavior was developed, and tested using path analysis. We proposed that the relationship between homemakers' role experiences (skill use, perceived financial equity, homemaking satisfaction, and role overload) and toddler's internalizing and externalizing behaviors is mediated by maternal psychological well-being (positive mood, negative mood, and cognitive difficulties) and parenting behavior (positive, punishing, and rejecting). Using confirmatory path analysis, the proposed model fit the data [Q = .73, W(34) = 47.4; p > .05] obtained from a sample of 187 homemakers. The results suggest that, as for employed mothers, it is important to understand how homemakers experience their role, because those experiences indirectly predict children's behavior. PMID- 8491934 TI - Subacute sinusitis: are antimicrobials necessary? AB - BACKGROUND: The need for antimicrobials in the treatment of subacute sinusitis was evaluated in 96 afebrile children who were prescribed antimicrobial (amoxicillin, amoxicillin clavulanate potassium, or trimethoprim sulfamethoxazole) or no antimicrobial medication in addition to a decongestant and saline nasal spray for 3 weeks. METHODS: Response was determined by complete clearing of the initial radiologic abnormalities or in the case of mucosal thickening, by a significant decrease in thickness to < 6 mm within the maxillary sinuses associated with improvement of the clinical signs and symptoms of sinusitis. If there was evidence of partial clearing by radiograph, the same therapy was continued for another 3 weeks. Nonresponders demonstrated no change or worsening of clinical and radiologic findings. RESULTS: Sixty-seven of the 96 subjects (70%) responded: 58 (87%) in 3 weeks and 9 (13%) in 6 weeks. Fifty-five of the responders were in the antimicrobial treatment group, and 12 were prescribed no antimicrobial medication. Twenty-nine of the 96 subjects (30%) did not respond to treatment; 22 received an antimicrobial and seven received no antimicrobial medication. CONCLUSIONS: The number of responders and nonresponders was similar in the antimicrobial- and nonantimicrobial-treated groups (p = NS), and no single antimicrobial medication demonstrated greater treatment effectiveness. PMID- 8491935 TI - Isolation and characterization of a recombinant heat shock protein of Aspergillus fumigatus. AB - BACKGROUND: Aspergillus fumigatus, a common environmental fungus, is responsible for a number of lung disorders, including allergy and infection, in human beings. For immunodiagnosis of these diseases, standardized, pure, and relevant antigens are not currently available. METHODS: A complementary DNA library of A. fumigatus was constructed with messenger RNA isolated from 96-hour-old culture of the organism. Fusion proteins expressed with the cDNA were characterized and evaluated. RESULTS: One of the clones, which reacted with both rabbit anti-A. fumigatus serum and a pool of sera from patients with allergic bronchopulmonary aspergillosis, expressed a 65 kd protein of A. fumigatus. The recombinant protein reacted with immunoglobulin E and immunoglobulin G antibodies in the sera from patients with allergic bronchopulmonary aspergillosis. The deduced amino acid sequence of the partially sequenced complementary DNA of the clone is homologous with the hsp 90 family of heat shock proteins in human beings and other organisms. CONCLUSION: The immunodominant nature and the homology to human heat shock proteins suggest a possible role for this protein in protective immunity and autoimmunity. PMID- 8491936 TI - Allergenicity of the mite, Blomia tropicalis. AB - BACKGROUND: Blomia tropicalis (BT) occurs in a significant percentage of homes in tropical and subtropical geographic regions of the United States and Europe and in countries in South America and Asia along with the pyroglyphid mites, Euroglyphus maynei (EM), Dermatophagoides pteronyssinus, and D. farinae. Blomia species may be major sources of allergens in house dust in addition to Dermatophagoides species and E. maynei. METHODS: Crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis were used to identify the antigens and allergens of BT and to determine the cross-reactivity between BT and the house dust mites, D. farinae, D. pteronyssinus, and the stored product mite, Tyrophagus putrescentiae. RESULTS: Homologous crossed immunoelectrophoresis of BT resulted in 27 antigen-antibody complexes. Crossed radioimmunoelectrophoresis of these gels showed 21 different immunoglobulin E binding antigens when they were incubated in the sera from 14 patients with asthma whose radioallergosorbent test and skin test results were positive. Heterologous crossed immunoelectrophoresis reactions with BT and rabbit D. farinae body and feces, D. pteronyssinus body and feces, and T. putrescentiae body and feces antisera resulted in one to four precipitin lines. BT extract, reacted with rabbit antisera produced against the bodies of D. farinae, D. pteronyssinus, and T. putrescentiae, produced 3, 2, and 4 antigenic peaks, respectively; whereas crossed radioimmunoelectrophoresis of these gels with the sera of the 14 patients with asthma resulted in immunoglobulin E binding to 2, 2, and 4 peaks, respectively. CONCLUSIONS: The results of this study indicated that BT contained multiple allergens of which most were species-specific. There was a limited amount of cross-reactivity between BT and the two common house dust mite species and the stored product mite. The amount of cross-reactivity appears to parallel the phylogenetic relatedness. PMID- 8491937 TI - Allergenicity of Euroglyphus maynei and its cross-reactivity with Dermatophagoides species. AB - BACKGROUND: The house dust mite, Euroglyphus maynei (EM), is common in homes in England, Europe, the southern United States, and other parts of the world. It is often present in densities greater than 100 mites per gram of dust. EM usually occurs with Dermatophagoides farinae (DF) and D. pteronyssinus (DP) and it is frequently more abundant than Dermatophagoides species. Therefore the allergenicity of EM and the cross-reactivity between EM and Dermatophagoides species are important considerations for diagnosis of mite-induced allergy and the use of appropriate immunotherapy. METHODS: Crossed immunoelectrophoresis revealed that EM was the source of at least 33 antigens. Crossed radioimmunoelectrophoresis with 32 different sera from patients with RAST results that were positive to EM and skin test results that were positive to both DF and DP identified 15 allergens. Individual sera recognized two to eight EM antigens as allergens. RESULTS: Ninety-one percent of the patients showed serum IgE directed at three or more allergens. Eighty-four percent of the patients had moderate or strong levels of IgE directed at antigen no. 33. All 15 allergens showed moderate or strong IgE binding by one or more sera. EM shared four and six cross-reacting allergens with DF and DP, respectively. Therefore 11 and 9 allergens of EM were species-specific and not shared by DF and DP, respectively. CONCLUSIONS: The results of this study clearly indicate that sensitivity to EM should be considered in geographic areas where this mite is abundant in homes. PMID- 8491938 TI - Comparison of Psilocybe cubensis spore and mycelium allergens. AB - BACKGROUND: Basidiospores are an important cause of respiratory allergy in mold sensitive atopic subjects. Collection of the large amounts of spores required for extract preparation is tedious and difficult. A desirable alternative could be mycelium grown in vitro if it is allergenically similar to spores. METHODS: Therefore this study compared the allergen contents of Psilocybe cubensis spore and mycelium extracts by different techniques with the use of pooled sera from subjects who had skin test and RAST results that were positive to P. cubensis spores. RESULTS: Isoelectric focusing immunoprints revealed six common IgE binding bands at isoelectric points 4.7, 5.0, 5.5, 5.6, 8.7, and 9.3. Two additional bands at isoelectric points 3.9 and 5.7 were detected only in the spore extract. Sodium dodecylsulfate-polyacrylamide gel electrophoresis immunoblots exhibited six common IgE-binding bands at 16, 35, 487, 52, 62, and 76 kd; 20 and 40 kd bands were present only in the spore extract. Although RAST and isoelectric focusing inhibition demonstrated that P. cubensis spore and mycelium extracts share many allergens, spores were allergenically more potent than mycelium. CONCLUSION: The results indicate that mycelium is a useful source of P. cubensis allergen, even though several spore allergens were not detected in mycelium. PMID- 8491939 TI - Allergens in school dust. I. The amount of the major cat (Fel d I) and dog (Can f I) allergens in dust from Swedish schools is high enough to probably cause perennial symptoms in most children with asthma who are sensitized to cat and dog. AB - BACKGROUND: We investigated the levels of Fel d I and Can f I in dust from tables, chairs, and floors in 29 classrooms in four Swedish schools. METHODS: School authorities were questioned about building characteristics, students were interviewed about their health and exposure to animals, and cleaning personnel were asked about methods and frequency of cleaning. Dust samples were taken from floors and horizontal surfaces of chairs and tables in all classrooms during a 6 week period. RESULTS: Higher amounts of Fel d I were found on chairs (geometric mean, 953 ng per gram of dust) than on tables (525 ng/gm) and floors (134 ng/gm). The concentration of Can f I (5.3 ng/gm) on chairs was 2 to 20 times higher than Fel d I. The concentration of Can f I (200 ng/gm) in dust from floors was twice as high as that of Fel d I. The concentration of Can f I on chairs was within the range previously found by other investigators in houses with dogs. CONCLUSIONS: Since the levels of both Fel d I and Can f I were much higher on chairs than on floors, we hypothesize that allergen is brought to schools on the clothes of students and teachers. We conclude that the levels of the two major allergens from furred pets (i.e., Fel d I and Can f I) in Swedish schools are probably high enough to sensitize children and to induce asthma in most children who are allergic to cats or dogs. PMID- 8491940 TI - Frequency of allergen-specific T lymphocytes in blood and bronchial response to allergen in asthma. AB - BACKGROUND: This study was designed to investigate whether the bronchial response to the sensitizing allergen in asthma is correlated with the frequency of allergen-specific T lymphocytes. METHODS: Twenty-three asthmatic patients sensitized to Dermatophagoides pteryonyssinus who had never received hyposensitizing therapy and 11 healthy control subjects were studied. Allergen specific T lymphocytes were enumerated in peripheral blood with limiting dilution cultures. Bronchial challenge with methacholine was performed in all subjects; patients with asthma also underwent an allergen bronchial challenge. Correlations between allergen-specific T cell frequencies and nonspecific bronchial hyperresponsiveness to methacholine as independent variables and early and late bronchial responsiveness to allergen challenge as dependent variables were investigated by means of stepwise-multiple regression analysis. RESULTS: We found that the frequency of allergen-specific T lymphocytes was higher than in control subjects in both patients with asthma with (p < 0.001) and those without (p < 0.05) late-phase asthmatic response to allergen. Moreover, the provocative does of allergen necessary to produce an early 15% fall of forced expiratory volume in 1 second could be predicted in part (59%) by an equation that incorporates methacholine sensitivity and allergen-specific T cell frequency. CONCLUSIONS: We conclude that allergen-specific T lymphocytes, which have an established influence on immunoglobulin E production, play an additional role in the induction of the bronchospastic response to inhaled allergen. PMID- 8491941 TI - Quantification of resident inflammatory cells in the human nasal mucosa. AB - BACKGROUND: To define the normal resident inflammatory cell population in the nasal mucosa, surgical specimens of human nasal turbinates were immunohistologically stained for various cell markers. METHODS: Freeze-dried paraffin-embedded sections were stained for lymphocyte cell-surface markers, and Carnoy's fixed sections were stained for mast cells and immunoglobulins. The numbers of stained cells were microscopically counted. RESULTS: T cells (CD3+ cells) were abundant in the lamina propria, and the number of CD4+ cells and CD8+ cells accounted for two thirds and one third of CD3+ cell number, respectively. Cells that stained for the alpha-chain of the interleukin-2 receptor (activated cells, CD25+) were limited and accounted for only 0.6% of CD3+ cell number. B cells (CD22+ cells) and monocytes and macrophages (CD14+ cells) were observed less frequently than T cells. Many immunoglobulin-producing cells were found in close proximity to the submucosal glands, and those cells were predominantly IgA+. Mast cells were widely distributed in the nasal mucosa, and about one third of these cells were stained for IgE molecules. Nonmast cells bearing IgE were rarely observed. CONCLUSION: Thus the dominant cell in the nasal mucosa is a CD3+, CD4+, CD25-lymphocyte. PMID- 8491942 TI - Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis with an operated aspergilloma. PMID- 8491943 TI - Pityrosporum ovale allergens in conventional house dust mite extracts? PMID- 8491944 TI - Intentional diagnostic insect sting challenges: a medical and ethical issue. PMID- 8491945 TI - The case for confirming occupational asthma: why, how much, how far? PMID- 8491946 TI - Do some patients with atopic dermatitis require long-term oral steroid therapy? PMID- 8491947 TI - Occupational asthma in a technologist exposed to glutaraldehyde. AB - BACKGROUND: Occupational asthma can be caused by several sterilizing agents, including glutaraldehyde, which has been shown to cause irritation of the eyes and upper respiratory tract and skin rash. We report a case of occupational asthma that was caused by exposure to glutaraldehyde. METHODS: To document the diagnosis of occupational asthma in a respiratory technologist, the following tests were performed: preshift and postshift spirometry, serial measurements of peak expiratory flow rate and nonspecific bronchial hyperresponsiveness, and workplace challenge test. RESULTS: Monitoring of peak expiratory flow rate showed improvement when the subject was away from the workplace. Improvements in forced expiratory volume in 1 second (FEV1) and provocative concentration causing a 20% fall in FEV1 were also observed. A workplace challenge test showed a progressive fall in FEV1 when the subject was exposed to glutaraldehyde in a sterilizing agent used to clean bronchoscopes at her workplace. After the diagnosis of occupational asthma was confirmed, the subject continued to assist with bronchoscopy but no longer cleaned the bronchoscopes. CONCLUSIONS: This case study illustrates the usefulness of a workplace challenge test in confirming the diagnosis of occupational asthma. It also indicates the importance of preventing or reducing exposure to sterilizing agents such as glutaraldehyde by means of effective ventilation and proper storage and enclosure during use. PMID- 8491948 TI - Exposure to domestic animals and risk of immunologic sensitization in subjects with asthma. AB - BACKGROUND: The objective of the study was to determine whether exposure to domestic animals plays a significant role, beyond atopy, in the development of immediate sensitization to animal-derived antigens. METHODS: To test this hypothesis, 200 subjects with asthma (85 male subjects and 115 female subjects; mean age, 37 +/- 16 years) seen consecutively in an asthma clinic were enrolled in a cross-sectional survey. Each subject answered a questionnaire about allergy symptoms and past and current exposure to domestic animals. Skin prick testing with extracts of common inhalant allergens including antigens from eight species of animal (cat, dog, horse, rabbit, rat, mouse, guinea pig, and hamster) were also carried out. RESULTS: Seventy-nine percent of subjects were atopic, and 91% had kept animals at home at some point (figures were 80% for dogs, 68% for cats, 23% for rabbits, and 20% for rodents). Using two-by-two tables, we showed that skin reactivity to at least one animal antigen was strongly linked to atopy (86% of atopic subjects had skin reactions as compared with 34% of nonatopic subjects: p < 0.001) but not to previous and current exposure to domestic animals (78% of both exposed and never exposed subjects). However, with the use of logistic regression, the determinants of skin reactivity to animals were atopy (p < 0.001), followed by cumulative duration of exposure to domestic animals (p < 0.01). The number of animals times the number of species times the duration of exposure was also a significant determinant of skin reactivity (p = 0.05). CONCLUSIONS: We conclude that beyond the predominant role of atopy, cumulative duration of exposure to domestic animals is a significant determinant for immediate sensitization to animal-derived antigens in subjects with asthma. PMID- 8491949 TI - Local nasal immunotherapy for Dermatophagoides-induced rhinitis: efficacy of a powder extract. AB - BACKGROUND: Local nasal immunotherapy by means of an extract in "macronized" powder from was studied in allergic rhinitis to Dermatophagoides species. METHODS: Twenty-four Dermatophagoides-sensitive patients were studied for 12 months in a double-blind controlled trial. Subjects were selected on the basis of a positive history, skin test, radioallergosorbent test, and intranasal challenge to Dermatophagoides antigen. Two 12-patient groups were selected at random; the first group was given active treatment, and the second received placebo. RESULTS: After 6 months, the mean weekly symptom and medication scores were significantly lower in the treated group than in the control group. The treated group had a significant increase of specific nasal threshold to Dermatophagoides antigen after treatment. Adverse reactions to local nasal immunotherapy, which were limited to the upper respiratory tract, occurred very rarely and did not interfere with dose schedule. CONCLUSION: Local nasal immunotherapy in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety. PMID- 8491950 TI - Bernadine Healy, MD, and the medical gender gap. PMID- 8491951 TI - Las comadronas. PMID- 8491952 TI - How women are changing medicine. PMID- 8491953 TI - Maternal employment and child care: a closer look. PMID- 8491954 TI - "Mommy track"--track or trick? PMID- 8491955 TI - Case study: pelvic inflammatory disease. PMID- 8491956 TI - Pilot study results. Falls among institutionalized elderly. AB - Increased cognitive impairment relates to poorer balance, to greater dependence in activities in daily living (ADL), and to perceptions of greater balance. Also, greater depression relates to better balance, to less dependence in ADL, and to perceptions of poorer balance. Those who fell were significantly younger and more dependent in ADL than residents who did not fall. However, there were no significant differences between these two groups for sex, length of institutionalization, depression, cognitive impairment, balance, or perceptions of balance. The findings that actual balance and perceptions of balance may not be congruent among cognitively impaired and depressed elderly has important implications for assessment and intervention. Perceptions are central to the decision of a person to ambulate or transfer and engage in other activities, and discrepancies between actual and perceived abilities may lead them to perform activities that they are unable to do safely. PMID- 8491957 TI - Gerontological research: use and application of focus groups. AB - In gerontology, focus groups are designed to obtain information from a small group of older adults about their feelings, opinions, and perceptions about a given problem, experience, service, program, or phenomenon. Although focus groups have many uses, they are best suited for exploratory qualitative research when the researcher is interested in learning more about a specific phenomenon. Advantages to using focus groups as a qualitative data collection technique include effective use of time, money, and effort; the benefit of group synergy; the ability to gain immediate validation of information by others in the group; and the ability to ask for direct clarification and to probe for deeper levels of information from the participants. Drawbacks of the focus group technique might include the researcher's group process techniques; the inability to generalize the findings to the population of interest; the breadth of information possible in one group sitting; and the time-consuming process of data transcription. PMID- 8491958 TI - Increasing cervical cancer screening among minority elderly. Education and on site services increase screening. AB - Older women participate in cervical cancer screening less regularly than do younger women. As a consequence, more lesions are found in more advanced and less curable stages in older women. Elderly black and Hispanic women have had lower rates of participation in cervical cancer screening than white women. There is a marked, inverse relationship between the stage of cervical cancer at diagnosis and the 5-year survival rate. The rate of cervical cancer screening among older women can be increased by offering education about Pap tests and onsite cervical cancer screening in housing for the elderly. PMID- 8491959 TI - Night shift: the restorative sleep specialists. PMID- 8491961 TI - The changing face of long-term care. PMID- 8491960 TI - Nursing the elderly. PMID- 8491962 TI - Older women: victims of rape. AB - Older female rape victims usually live alone, are raped by strangers, experience physical force and injury, and also are robbed. Rape trauma syndrome, a nursing diagnosis, consists of an acute phase of disorganization, and a long-term phase of reorganization of the victim's lifestyle. Rape victims experience emotional, physical, and cognitive reactions to the trauma of rape. Nursing actions can include providing specific interventions to victims during the acute phase, identifying victims during routine exams, referring victims for ongoing counseling, conducting community education programs on primary prevention and available services, and participating in longitudinal rape studies. PMID- 8491963 TI - An overview of the pathophysiology and management of portal hypertension and ascites. PMID- 8491964 TI - The natural history of varices. AB - Variceal bleeding and its ensuing complications correlate positively with the severity of liver disease. The average risk of bleeding in patients with cirrhosis who have not previously bled is 30%, with a 50% mortality rate within 6 weeks. This mortality rate is the rationale for prophylaxis. However, although fatal bleeding causes 35% of all deaths, patients who die after the first episode of bleeding represent only 15% of patients with cirrhosis and varices. Portal and intravariceal pressure, the appearance of oesophageal varices on endoscopic examination, severity of liver disease and alcohol abuse are independent risk factors for the occurrence of the first bleeding episode. In sinusoidal portal hypertension, the presence of varices indicates a hepatic venous pressure gradient > or = 12 mmHg. Although hepatic venous pressure gradient tends to be higher in patients who bleed or have large varices, bleeding risk is not related linearly to pressure above this threshold. Tension on the variceal wall relative to varix radius may be critical and increasing variceal size, in conjunction with wall thinness, may favour rupture at lower intraluminal pressures. The North Italian Endoscopic Club's simplified index for the risk of a first bleeding episode is based on Child class, variceal size and presence of red wale markings, although there may be other independent risk factors. Abstention from alcohol can decrease variceal size and the number of cherry-red spots. Because large varices are unlikely to develop de novo within 2 years, biennial endoscopic screening is sufficient for patients without varices; annual endoscopy is recommended for those with small varices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491965 TI - Paracentesis in the management of cirrhotic ascites. AB - During the last few years, several studies including six randomised, controlled trials reevaluating therapeutic paracentesis in the management of cirrhotic patients with tense ascites have been reported. The main findings of these investigations are: (i) Repeated large-volume paracentesis (evacuation of 4-6 l/day until complete mobilization of ascites) or total paracentesis (complete mobilization of ascites in only one tap) associated with i.v. albumin infusion (6 8 g/l of ascitic fluid removed) are more effective in eliminating the intra abdominal fluid than conventional diuretic therapy, are associated with a lower incidence of complications and considerably reduce the duration of hospital stay and the cost of treatment; (ii) The mobilization of ascites by paracentesis without albumin infusion is associated with an impairment in effective circulating blood volume, as indicated by a decrease in cardiac output, central venous pressure, pulmonary capillary wedge pressure and plasma concentration of atrial natriuretic peptide and a marked elevation of plasma renin activity and aldosterone concentration. In 20% of patients this circulatory disturbance is accompanied by the development of renal impairment and/or dilutional hyponatraemia. These changes can be detected within the first 24 h following complete mobilization of ascites and do not occur when plasma volume is expanded with albumin; (iii) Hemaccel and dextran 70 appear to be as effective as albumin in preventing renal and electrolyte complications after paracentesis; (iv) Therapeutic paracentesis is an alternative treatment to peritoneovenous shunting in cirrhotic patients with refractory ascites. PMID- 8491966 TI - Plasma volume contraction in portal hypertension. AB - The effect of blood volume contraction induced by a 4-week regimen of spironolactone (100 mg/day) or furosemide (40 mg/day) on the hepatic venous pressure gradient (HVPG), an indicator of portal hypertension, was evaluated in patients with cirrhosis and no ascites. In the spironolactone group (n = 15), HVPG decreased significantly from 16.5 +/- 0.9 mmHg (mean +/- S.E.M.) to 12.9 +/- 1.0 mmHg (P < 0.005) and total blood volume contracted significantly from 4338 +/ 231 ml to 4006 +/- 203 ml (n = 14, P < 0.01). Although the HVPG changes did not correlate significantly with changes in measured total blood volume or in simultaneously determined systemic haemodynamics, a significant inverse correlation (r = -0.74, P < 0.01, n = 12) was found between the HVPG change and posttreatment plasma aldosterone levels, attesting to the effectiveness of spironolactone therapy in lowering HVPG. In the furosemide group (n = 10), neither HVPG (13.7 +/- 0.3 mmHg vs. 13.6 +/- 0.9 mmHg) nor total blood volume (4961 +/- 153 ml vs. 4964 +/- 162 ml) declined significantly. These results show that long-term administration of spironolactone to patients with cirrhosis and no ascites produced a significant reduction in HVPG that may have been due to gradual, sustained volume contraction. Thus, spironolactone may prove to be an effective treatment for portal hypertension in cirrhosis without ascites. PMID- 8491967 TI - Mechanism of sodium retention and ascites formation in cirrhosis. AB - Renal sodium and water retention and ascites associated with cirrhosis develop in the setting of severe sinusoidal portal hypertension, hyperdynamic circulation (characterized by arterial hypotension, hypervolaemia, high cardiac output and low peripheral vascular resistance), homeostatic activation of the renin angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone production (i.e. mechanisms designed to maintain arterial pressure within normal limits) and marked increase in hepatic and splanchnic lymph production that overcomes the transport capacity of the lymphatic vessels to the general circulation, leading to leakage of fluid within the peritoneal cavity. Splanchnic arteriolar vasodilation and the increased splanchnic blood flow that characterize portal hypertensive states could be a major factor in the pathogenesis of cirrhotic ascites because it may account for the hyperdynamic circulation, the activation of endogenous neurohormonal systems that cause sodium and water retention and, also, by altering of splanchnic capillary haemodynamics and permeability, the excessive production of lymph in this vascular territory. PMID- 8491968 TI - The management of active variceal bleeding. AB - A systematic review of available treatments for controlling active variceal bleeding provides important guidelines for choosing an overall strategy. The initial prerequisite of a diagnostic endoscopy provides the opportunity for early intervention with local endoscopic techniques, such as injection sclerotherapy, direct intravariceal injection of tissue adhesives and banding ligation of varices. This approach currently represents the optimal strategy. If the endoscopic expertise is not available, the use of vasoactive drugs may provide temporary control of bleeding while allowing time for more definitive treatment. Vasopressin and its analogues are the most widely used vasoactive drugs, but somatostatin holds promise. In view of the systemic haemodynamic complications associated with vasopressin (and probably glypressin), these drugs should be given in combination with nitrates. Balloon tamponade remains an important alternative for patients in whom massive, life-threatening haemorrhage has occurred. Surgical techniques, such as shunting and devascularisation, are increasingly reserved for the management of variceal bleeding that endoscopic therapy has failed to control. PMID- 8491969 TI - Hyperdynamic state in chronic liver diseases. AB - Reduced splanchnic arteriolar resistance and increased portal venous outflow have been associated with chronic portal hypertension. This hyperdynamic splanchnic circulatory state is accompanied by a hyperdynamic systemic circulation characterized by a high cardiac index and low systemic vascular resistance. The systemic phenomenon occurs earlier than the regional one, possibly because the increased outflow resistance induced by portal hypertension delays the effect of circulating humoral vasodilators on the splanchnic bed. Several vasoactive substances have been advanced as the vasodilator responsible for the hyperdynamic circulation. Glucagon and bile acids have been found to be potent splanchnic vasodilators in animal studies. However, neither consistently dilates other vascular beds. For example, bile acids are splanchnic--but not systemic- vasodilators. Several studies suggest a role in chronic liver disease for nitric oxide, a potent endogenous vasodilator secreted by endothelial cells. Prostaglandins have also been proposed as the responsible vasodilator. However, mixed results have been seen with experimental suppression of prostaglandin synthesis. For a hyperdynamic state to develop and persist requires not only reduced cardiac afterload, but also an increased venous return. Recently, we found an expanded plasma volume after initial vasodilation in rats with portal hypertension. This 'refill' of the circulation may be intrinsic to development of the hyperdynamic state. Furthermore, this blood volume expansion may be the link between vasodilation and the hyperdynamic circulation. PMID- 8491970 TI - Medical treatment of ascites in cirrhosis. AB - Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of 'simple' ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/dl, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor. PMID- 8491971 TI - Chloramphenicol resistant enteric fever. AB - In recent times there have been several reports of chloramphenicol resistant enteric fever necessitating the use of other antimicrobial agents. Clinical profile of 15 chloramphenicol resistant patients of enteric fever was studied. Three such patients (20%) responded to chloramphenicol despite in vitro resistance to the drug. Hence chloramphenicol still remains the drug of first choice in enteric fever as a majority (68.4%--26 out of 38) of our bacteriologically proven enteric fever patients were cured by the drug. The remaining 12 cases responded satisfactorily to ciprofloxacin (46.7%), gentamicin (20%), and ofloxacin (13.3%). There was an increased incidence of complications among the 15 drug resistant cases as compared to 23 cases of chloramphenicol sensitive enteric fever observed during the same period. PMID- 8491972 TI - Squatting position for delivery. AB - The study was conducted on 200 normal pregnant women who were randomly classified into 2 groups of 100 cases each. The control group comprised mothers in supine position throughout labour and delivery (46 primigravidae and 54 multigravidae). The squatting group consisted of cases who were kept ambulatory during the 1st stage and were asked to squat on ordinary delivery cots during the 2nd stage of labour. Third stage of labour was conducted in supine position. The squatting group comprised 42 primigravidae and 58 multigravidae. There was a mean difference (shortening) of 3 hours in primigravidae and 2 hours in multigravidae in the duration of 1st stage of labour between the squatting and control groups. In the duration of 2nd stage of labour the mean differences in primigravidae and multigravidae of the squatting and control groups were 20 and 13.5 minutes respectively. In the squatting group there were 79 normal vaginal delivery, 16 forceps delivery and 5 caesarean sections whereas in the control group there were 80, 18 and 2 cases respectively. Although foetal complications were comparable in both the groups, the incidence of maternal injuries was observed in 14 cases in control group and 38 cases in squatting group. It was concluded that without proper birthing chairs which can give good perineal support, the usual supine position is preferable. PMID- 8491973 TI - Mortality profile in trauma victims. AB - To assess the mortality incidence among trauma victims a one year prospective study was conducted on all patients admitted with physical trauma. The causes of death amongst trauma victims comprised road traffic accident (44.71%), thermal injuries (19.71%), domestic causes (11.54%), agriculture related injury and criminal violence (9.61% each), fall of construction workers (2.4%), collapse of buildings and train accidents (0.96% each) and industrial injury (0.48%). Mortality was highest among victims with multiple injuries (41.35%). The mortality rate increased in direct proportion to increase in transportation time and injury severity score. PMID- 8491974 TI - Pseudosarcomatous myofibroblastic proliferation in urinary bladder. PMID- 8491975 TI - Conventional operation versus keyhole surgery. PMID- 8491976 TI - Modern prophylactic treatment of animal bite cases. PMID- 8491977 TI - Labial agglutination. PMID- 8491978 TI - Review of unwanted pregnancy in teenagers. PMID- 8491979 TI - Urine culture in paediatric practice. PMID- 8491980 TI - Thumb sucking: practitioners' guidelines. PMID- 8491981 TI - New era of antirabic vaccine. PMID- 8491982 TI - Clinicomycological study of candidiasis. AB - Opportunistic pathogens like candida are responsible for a major cause of morbidity and mortality in the chronically debilitated and the immunocompromised patient. The clinical data of 100 patients from whom candida species were repeatedly isolated were analysed. Most of the patients (40%) were above 51 years. Postoperative patients (34%) and patients with diabetes mellitus (30%) had a high incidence of candidiasis. All these patients had either long standing indwelling catheters or were on prolonged antibiotics, steroids or cytotoxic drugs as a part of the management for the underlying cause. Candida albicans (38.9%) and Candida stellatoidea (37.1%) were the most common species isolated. Maximum isolation was from urine (140) mostly obtained from patients with indwelling urinary catheters for more than a week or so. None received antifungal therapy except four, two of them died in spite of appropriate antifungal therapy. PMID- 8491983 TI - Use of calcium antagonist (nifedipine) in premature labour. AB - Effectiveness of nifedipine in suppressing premature uterine activity was studied on 20 normal pregnant women who received, depending on the frequency of uterine contractions and degree of cervical dilatation, 5-10 mg nifedipine orally 8 hourly till the uterine contractions were abolished followed by 5 mg 12 hourly up to 38 weeks of gestation. Another 20 age, gravida and gestational period matched normal pregnant women received 10 mg isoxsuprine hydrochloride orally 8 hourly till the uterine contractions were abolished, followed by 10 mg 12 hourly up to 38 weeks of gestation. Successful tocolysis was observed in 85% of cases receiving nifedipine in contrast to 40% of women receiving isoxsuprine hydrochloride. The mean time from presentation to delivery and mean birth weight were 21.8 days and 2510 g respectively in isoxsuprine hydrochloride treated cases and 34.2 days and 2750 g respectively in cases treated with nifedipine. In either group there were no serious untoward effects on mother, labour and baby. PMID- 8491984 TI - Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. AB - Acitretin has recently been introduced to replace etretinate in the treatment of severe psoriasis due to a considerable shorter terminal half-life. The previously recommended 2-month anticonceptive period after acitretin treatment has been extended to 2 years after the detection of etretinate in certain acitretin recipients. In the present study, 10 patients with severe psoriasis were treated with 30 mg acitretin daily for 3 months. Seven patients had detectable mean steady-state plasma etretinate concentrations in the range of 2.5 to 56.7 ng/ml. Four of the patients showed teratogenic levels of plasma etretinate. Consumption of alcohol appeared to be an important contributing factor for the formation of etretinate. As judged from the dose- and body-weight-normalized AUC values (AUCcor) there was a great inter-individual variation (sixfold) in the systemic availability of acitretin. After discontinuation of therapy, the rate of elimination of both acitretin (t1/2 range 1.0 to 25.4 d) and 13-cis-acitretin (t1/2 range 1.5 to 25.7 d) was found to be related to the observed mean steady state level of etretinate as evidenced by a longer terminal t1/2 of patients with high levels of etretinate in plasma. A mean terminal elimination half-life of etretinate was found to be 45.7 d +/- 10.6 (mean +/- SD; range 27.0 to 59.3 d). The risk of metabolic formation of etretinate in acitretin recipients makes it impossible to draw any definite conclusion with regard to recommendation of length of anticonceptive period following acitretin therapy in psoriatics. Monitoring of plasma etretinate levels in acitretin-treated fertile women is advisable. PMID- 8491985 TI - TGF alpha enhances locomotion of cultured human keratinocytes. AB - A cDNA sequence coding for the full-length human transforming growth factor alpha (TGF alpha) precursor protein was introduced into and transcribed in cultured human keratinocytes, using a high-titer, high-expression, murine amphotropic retrovirus. Keratinocytes were shown capable of post-translationally modifying the TGF alpha primary translation product, with the subsequent formation of several cell-associated and secreted forms of TGF alpha, at least five of which, including the 50 amino acid mature species, can potentially bind and activate the epidermal growth factor receptor. Cells overexpressing the TGF alpha gene assumed a spindled morphology with long, bipolar filamentous processes and displayed increased locomotion. The soluble, mature form of TGF alpha alone also could induce the observed changes in cell shape and motility when added to keratinocyte cultures exogenously. The effects were dose dependent, and up to fourfold increases in locomotion were caused by TGF alpha in the absence of bovine pituitary extract (BPE). The addition of BPE to high concentrations of TGF alpha further enhanced keratinocyte motility to eightfold over baseline, suggesting a synergistic interaction between the two factors. These experiments demonstrate that keratinocytes can synthesize several forms of TGF alpha and that TGF alpha, besides being mitogenic, may have other important regulatory functions in keratinocytes. PMID- 8491986 TI - Epidermal growth factor and insulin-like growth factor I enhance keratinocyte migration. AB - Although their mechanisms of action are unclear, a number of growth factors has been shown to promote cutaneous wound repair. Keratinocyte migration and proliferation are required for re-epithelialization, and there is evidence to suggest that these processes may be regulated by one or more growth factors that promote wound repair. Using the phagokinetic assay, which allows direct observation of migration path as a gold-particle-free area, we examined the effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on human keratinocyte migration. Addition of EGF to defined medium in the absence of any other growth factor induced an increase in migration of 2.5-4.5 fold after overnight incubation; the effect of EGF on migration was concentration dependent, with a maximum at 10 to 50 ng/ml EGF. Concentration-dependent enhancement of keratinocyte migration was similarly observed with IGF-I as well as insulin. With all factors, migration was observed on colloidal gold plates coated with collagen IV or with fibronectin but not in the absence of matrix coating. To examine further the involvement of the EGF receptor in keratinocyte migration, we tested the effect of a monoclonal antibody to the EGF receptor that acts as an antagonist. EGF-induced migration was completely prevented by this antibody; however, the enhancement by insulin or IGF-I was not blocked. These results suggest that IGF-I and insulin enhance keratinocyte migration by a mechanism distinct from that of EGF. PMID- 8491987 TI - Role of integrin alpha 2 beta 1 (VLA-2) in the migration of human melanoma cells on laminin and type IV collagen. AB - The random cell migration of four human melanoma cell lines on laminin and type IV collagen-coated substrates was studied by video time-lapse image analysis and compared to the expression of a number of beta 1 integrins including alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 using flow cytometry. These integrins were heterogeneously expressed in the four cell lines tested with three of four lines expressing alpha 2 beta 1. The melanoma cell line that did not express alpha 2 beta 1 exhibited weak attachment and low cell migration rate on both laminin and type IV collagen, whereas the other melanoma cell lines showed an increase in attachment and mean cell migration rate in a dose-dependent manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by function blocking anti-beta 1 and anti-alpha 2 monoclonal antibodies (p < 0.001) but not by function blocking anti alpha 3 and anti-alpha 6 monoclonal antibodies. Image analysis of the cells before and after treatment with anti-beta 1 and anti-alpha 2 MoAb indicated that the inhibition of migration did not result in detectable cell detachment, retraction of cell processes, or other significant cell-shape change. Taken together, the findings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely mediated by integrin alpha 2 beta 1. PMID- 8491988 TI - 12-O-tetradecanoylphorbol-13-acetate not only modulates proliferation rates, but also alters antigen expression and LAK-cell susceptibility of normal human melanocytes in vitro. AB - For serial cultivation of normal human melanocytes media supplemented with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) are largely employed. By using a culture medium that permits cultivation of melanocytes without TPA, the effects of TPA on melanocyte proliferation, phenotype, and susceptibility to lymphokine-activated killer cells were studied. Addition of 50 ng/ml TPA to the medium induced rapid dendrite formation and increased the cell proliferation rate by 16-63% in mitogen-rich media (four of seven cultures, p < 0.01), and by 237% in mitogen-reduced media (p < 0.001). Furthermore, several phenotypic changes indicating early stages of melanocyte transformation were induced by 50 ng/ml TPA. These included increased expression of melanoma progression-associated antigens such as A.1.43 and A.10.33, upregulation of nerve-growth factor receptor as well as of the melanocyte-activation marker HMB-45 and of histocompatibility class I antigens. In contrast, the expression of the differentiation marker K.1.2 and of intercellular adhesion molecule-1 was decreased in TPA-treated cultures. Most of these changes persisted even after removal of TPA from the culture medium (> or = 2 weeks). Staurosporine, a protein kinase C inhibitor, modulated melanocyte-antigen expression similar to TPA, suggesting that protein kinase C downmodulation rather than activation by TPA is involved. In addition to the antigenic alterations, the susceptibility of TPA-treated melanocytes to lymphokine-activated killer cell cytotoxicity decreased by 40% (p < 0.01), possibly due to their altered surface antigen expression. The presented data reveal that the tumor promoter TPA hitherto used as a supplement of melanocyte culture media induces profound phenotypic and functional changes of the cultured cells, indicating incipient transformation of normal human melanocytes in vitro. PMID- 8491989 TI - Spironolactone directly inhibits proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5 alpha-dihydrotestosterone in vitro. AB - Spironolactone produces antiacne effects and has recently been shown to inhibit 5 alpha-dihydrotestosterone (5 alpha-DHT) receptors in human sebaceous glands. We applied spironolactone alone and combined with testosterone and 5 alpha-DHT to investigate its effects on the proliferation of human sebocyte cultures derived from facial skin. Secondary human facial sebocytes in 96-well culture plates were treated for 10 d by a single or combined application of testosterone (10(-8)-10( 5) M), 5 alpha-DHT (10(-8)-10(-5) M), and spironolactone (10(-12)-10(-7) M) in serum-free basal medium. Cell proliferation was assessed in six wells using a fluorometric assay. Testosterone and 5 alpha-DHT significantly stimulated sebocyte proliferation in a dose-dependent manner, the effect being strongest with 5 alpha-DHT. Spironolactone, on the other hand, caused a dose-dependent inhibition (25% and 50% at 10(-9) and 10(-7) M, respectively). Combined treatment of human facial sebocytes with spironolactone and testosterone or 5 alpha-DHT resulted in a lower proliferation than with androgens alone. The fact that spironolactone directly and dose dependently inhibits the proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5 alpha-DHT at the cellular level is indicative of a receptor-mediated effect. PMID- 8491990 TI - In vivo cytokine expression in normal and perturbed murine skin--analysis by competitive quantitative polymerase chain reaction. AB - Although cells from both epidermis and dermis have been shown to produce a variety of soluble mediators in vitro, it is not clear whether this reflects the in vivo situation. To study in vivo cytokine expression, whole skin as well as dispase-separated epidermis and dermis from normal adult mice were prepared and snap-frozen immediately. RNA was then extracted and analyzed both by conventional and by competitive quantitative polymerase chain reaction. Molecular analysis showed that murine skin in vivo constitutively expresses several cytokine genes at moderate (e.g., interleukin-1 alpha) or low (e.g., interleukin-6 and granulocyte-macrophage colony-stimulating factor) abundance. A striking, rapid upregulation was observed for some of these cytokines in the process of tissue separation. Of interest, the epidermal and dermal compartments exhibited different induction patterns: interleukin-1 alpha, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-alpha expression were detected preferentially in the epidermis, whereas upregulation of interleukin-6 was found to be most prominent in the dermis. This pattern of cytokine expression was also reflected in supernatants generated from the respective single-cell suspensions. Thus, this study determines the baseline in vivo cytokine expression in the skin and the occurrence of immediate, compartment-specific alterations on perturbation. These data should contribute to our understanding of both skin homeostasis and the host-defense mechanisms initiated following injury to this organ. PMID- 8491991 TI - Subclass reactivity of pemphigus foliaceus autoantibodies with recombinant human desmoglein. AB - Pemphigus foliaceus (PF) and its endemic form, Fogo Selvagem (FS), are autoimmune disorders characterized by subcorneal vesicles and IgG4 subclass autoantibodies that recognize a surface antigen of normal epidermal cells. FS and PF autoantibodies have been shown to bind desmoglein (DGI), a desmosomal glycoprotein classified as a member of the cadherin family of calcium-dependent cell adhesion molecules. In the present study we report the isolation of three overlapping cDNA clones representing greater than 90% of the extracellular domain of human DGI. Recombinant proteins encoded by these clones, designated DGI-1, DGI 2, and DGI-3, were produced in bacteria and analyzed for immunoblot (IB) reactivity with a panel of FS, PF, and control sera. FS and PF autoantibodies possessing reactivity with each of the three recombinant fusion proteins (FPs) were identified. FP DGI-3 (containing 123 amino acids of the membrane proximal region of the DGI ectodomain) showed reactivity with the largest number of patient sera--seven FS and one PF. IB reactivity with the DGI-1 FP (encoding 205 amino acids of the N-terminal region of DGI) could be eliminated by truncation of the C-terminal portion of this protein, indicating that autoantibodies were not binding the R-A-L motif. Autoantibodies reactive with two of the three FPs were predominantly restricted to IgG4, the subclass shown to be pathogenic in the passive transfer mouse model. The findings of this study demonstrate that the extracellular domain of DGI contains at least three antigenic sites recognized by FS and PF autoantibodies. The region near the membrane-spanning domain of DGI appears to contain an immunodominant site. This study is the first to document immunoblot reactivity of FS and PF autoantibodies with recombinant forms of DGI. The use of such molecular tools should facilitate the identification and characterization of relevant antigen/antibody systems in FS and PF. PMID- 8491992 TI - Ultraviolet A-induced lipid peroxidation and antioxidant defense systems in cultured human skin fibroblasts. AB - Cultured human skin fibroblasts from healthy donors were irradiated with 180 kJ.m 2 ultraviolet (UV) A (320-400 nm) and assayed for thiobarbituric acid-reactive substances (TBARS), taken as an indicator of lipid peroxidation. Antioxidant defenses, including total glutathione (GSH) levels, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (Cat) activities were simultaneously assayed before and after irradiation. For the various donors, with different activities of these antioxidant systems before irradiation, TBARS correlated positively with SOD activity and negatively with Cat activity, whereas no correlation with GSH level or GSHPx activity was found. These data support the view that O2- is generated by UVA irradiation. They also suggest that H2O2, arising from O2- dismutation by SOD is not completely removed by Cat. Thus, the sensitivity of human fibroblasts to UVA-induced lipid peroxidation depends on a balance between SOD and Cat activities. After UVA irradiation, Cat activity was strongly inhibited, whereas GSH level was slightly decreased. By contrast, GSHPx and SOD activity remained unchanged after UVA irradiation. PMID- 8491993 TI - Apoptotic index: discriminant feature for the differentiation of cutaneous diffuse malignant follicular center cell lymphomas from lymphoid hyperplasia. AB - Diffuse subtypes of cutaneous lymphoid hyperplasia (CLH; n = 18) and primary malignant follicular center cell lymphoma of the skin (FCCL, n = 11) were diagnosed by conventional histology, immunophenotyping on paraffin sections, and gene rearrangement analysis. We then counted on semithin, Azur A-stained sections of resin-re-embedded biopsy specimens the relative numbers of apoptotic bodies among all lymphoid cells (apoptotic index [AI]). The diagnostic value of AI was compared to that of mitotic indices (MI) and percentages of various cell types in the cutaneous infiltrate. Features of cellular infiltrates distinguishing to two groups of lesions, in the order of decreasing significance, were percent large lymphoid cells, percent medium-sized lymphoid cells (both higher in FCCL); percent small lymphoid cells, percent epithelioid/giant cells, and percent histiocytes/macrophages (all three higher in CLH). However, of all parameters tested, AI had the greatest discriminant value (median in FCCL 1.11%, in CLH 0.14%; p = 8 x 10(-6)). Two cases, diagnosed as CLH with all morphologic and immunologic methods used, showed B-cell monoclonality at the DNA level. Linear discriminant analysis determined the following order of distinctive power of variables: 1) AI; 2) MI; 3) percent small lymphoid cells; 4) percent medium-sized lymphoid cells; 5) percent large lymphoid cells; 6) percent epithelioid/giant cells; and 7) percent histiocytes/macrophages. The present study thus establishes AI as an important parameter in the differentiation of diffuse CLH from diffuse cutaneous FCCL. PMID- 8491994 TI - Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification. AB - We present further evidence in support of the notion that Borrelia burgdorferi is possibly involved in the pathogenesis of morphea and lichen sclerosus et atrophicus (LSA). Running a nested polymerase chain reaction (PCR) with a primer set specific for the flagellin gene of B. burgdorferi enabled us to demonstrate the presence of Borrelia DNA in skin biopsies of patients with morphea (nine of nine) of LSA (six of six). Biopsy specimens obtained from patients with erythema chronicum migrans (two patients, four of four samples) and acrodermatitis chronica atrophicans (one patient, one of one sample) also showed positive PCR results. By contrast, there was no amplification of Borrelia DNA in control biopsies either from patients with chronic eczema (three of three) or psoriasis (two of two) or from normal skin (three of three). Antibodies directed against B. burgdorferi were only detected in the serum of patients with erythema chronicum migrans (two of two) and acrodermatitis chronica atrophicans (one of one) but were not present in cases of morphea (five of five), LSA (three of three), or in control subjects (three of three). These data suggest that B. burgdorferi may play a role in the pathogenesis of both morphea and LSA. Furthermore, we conclude that PCR analysis provides an important diagnostic tool, even in seronegative Borrelia infections. PMID- 8491995 TI - Chronic wounds: pathophysiologic and experimental considerations. PMID- 8491996 TI - Transcranial Doppler with contrast injection for the detection of patent foramen ovale in stroke patients. AB - Right-to-left shunt through a patent foramen ovale was searched for in 80 patients with acute ischemic stroke by simultaneously performing transthoracic two-dimensional echocardiography and transcranial Doppler during agitated saline injection. A patent foramen ovale was detected by echocardiography in 14 patients (17.5%). Transcranial Doppler correctly identified all 14 patients, and 7 more patients in whom echocardiographic findings were indeterminate. Prevalence of patent foramen ovale by transcranial Doppler was therefore 26.3% (21 of 80 patients). Concordance between the two tests was 91.3% (73 of 80 patients). The delivery of contrast material to cerebral vessels is therefore demonstrable by transcranial Doppler in all patients diagnosed by contrast echocardiography, suggesting that paradoxical embolization through a patent foramen ovale may be more frequent than previously thought. Transcranial Doppler with contrast injection is a valid alternative in case of poor echocardiographic image quality. PMID- 8491997 TI - Flow quantitation by contrast echocardiography. Effects of intervening tissue and of the angle of incidence between flow and ultrasonic beam. AB - The combination of a standardized echographic contrast agent with the analysis of the ultrasonic radio frequency (RF) signal allowed in vitro flow quantitation in a circulation model. The purpose of this study was to investigate both the effects of biological tissues, intervening between probe and insonated structure, and the effects of the angle of incidence between flow and ultrasonic beam on RF flow quantitation. Thus, the contrast agent SHU 454 was intravenously injected (0.4 ml) as a bolus into a circulation model, at variable flow rates, while keeping the pressure and volume of the vessel constant. Injections were performed with saline interposed between probe and vessel and after the addition of the subcutaneous tissue of a pig; injections were also performed using the probe normal to the flow and with an angle of incidence of 45 degrees. Echographic data were recorded by a mechanical sector scanner, capable of sampling the RF signal from a region of interest positioned in the center of the vein. Contrast echo time-intensity curves were generated. As expected, both peak intensity and the area under the curves decreased with intervening tissue (-58 and -70% of baseline values, respectively, p < 0.001). Surprisingly, mean transit time also decreased with intervening tissue (from 1.12 +/- 0.25 seconds with saline, to 0.92 +/- 0.13 seconds with tissue, p < 0.001), thus producing a systematic overestimation of flow (21% on the average). To compensate for signal attenuation, contrast injections were repeated in the presence of tissue after increasing the electronic signal amplification (10 dB), and transit time did not significantly differ from control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8491998 TI - Quantitative angiographic follow-up studies on the development of coronary artery disease: which coronary segments should be analyzed? Experience from INTACT. AB - Angiographic follow-up studies on the evolution of coronary artery disease are of increasing relevance. It has still to be evaluated which coronary segments are predominantly involved in the process of atherosclerosis and, thus, should be preferably included in the analysis. Therefore, the correlation of progression and regression of coronary disease with the diameter and location (proximal, mid or distal) of coronary segments was investigated from the data of the INTACT study, in which 25 different coronary segments were defined including anatomic variants of rather distal segments. In 348 patients with coronary artery disease, standardized coronary angiograms were repeated within 3 years and were quantitatively analyzed (CAAS). In 1063 coronary stenoses (% diameter stenosis > 20%) compared from both angiograms, progression and regression were not influenced by diameter nor location of arterial segments. In the follow-up angiograms, the number of new lesions (stenoses and occlusions) per coronary segment differed with regard to segment diameter (> 3 mm: 64/1125 (6%); 2-3 mm: 139/1967 (7%); < 2 mm: 44/1756 (2%); p < 0.001) and location of segments (proximal: 86/1285 (7%); mid: 84/1193 (7%); distal: 77/2370 (3%); p < 0.001). Out of 77 distal new lesions, only 25 (32%) were found in segments < 2 mm in diameter. Since the absolute number of new lesions was high in distal coronary segments, but low in segments with diameters < 2 mm, angiographic follow-up studies should analyze coronary segments at any location, but may neglect segments with diameters smaller than 2 mm. PMID- 8491999 TI - Global and regional parameters of left ventricular performance in healthy subjects during rest and exercise assessed by radionuclide ventriculography. AB - The aim of our study was to analyze numerous global and regional parameters of left ventricular (LV) performance during rest and exercise, in the group of 14 healthy subjects, by quantitative gated equilibrium ventriculography in left anterior oblique view (45 degrees). The global LV parameters at rest vs. exercise in our study were: heart rate 68.9 +/- 18.4 vs. 137.5 +/- 38.6; systolic blood pressure (mmHg) 121.8 +/- 18.2 vs. 178.6 +/- 31.2; diastolic blood pressure (mmHg) 82.1 +/- 10.8 vs. 90.7 +/- 12.4; double product 8,368.6 +/- 2,308.8 vs. 24,589.3 +/- 8,357.8; global ejection fraction (%) 61.9 +/- 15.4 vs. 72.8 +/- 12.8, end-diastolic volume index (ml/m2) 82.5 +/- 23.2 vs. 96.9 +/- 27.8; end systolic volume index (ml/m2) 31.8 +/- 19.8 vs. 26.9 +/- 15.4; stroke volume index (ml/m2) 50.6 +/- 17.6 vs. 70.0 +/- 22.6; peak emptying rate (EDV/s) 3.4 +/- 2.6 vs. 8.3 +/- 3.8 and peak filling rate (EDV/s) 3.6 +/- 2.6 vs. 9.6 +/- 3.8. A significant difference (p < 0.05) between rest and exercise was found for all parameters. The highest values of LV regional ejection fraction were found in anterolateral and posterolateral region, while the lowest values were observed in inferoseptal and inferior regions. During exercise a significant increase of regional ejection fraction was found in all regions. The highest percent of radius shortening during rest was in anterolateral and posterolateral regions, and lowest in inferoseptal and inferior regions. The same sequence was found during exercise, and the difference in percent of radius shortening, between rest and exercise was significant in all regions. The observed normal values of global and regional parameters of LV function during rest may serve as a contribution for referent values. Our results on regional ejection fraction and the percent of radius shortening in rest, and their change during exercise, offer the possibility of additional information in the investigation of cardiac patients by means of radionuclide ventriculography. PMID- 8492000 TI - Evaluation of regional myocardial systolic and diastolic function using ECG-gated Sestamibi scintigraphy. Preliminary results in patients with and without coronary artery disease. AB - Sestamibi allows ECG-gated acquisition and similarly to radionuclide angiography a time-activity curve from a defined myocardial region can be derived and analysed. Diastolic (peak relaxation velocity) and systolic (per cent thickening) functional parameters from Sestamibi ECG-gated acquisition were obtained; this data were compared in 10 patients with radionuclide angiographic data (peak filling rate and ejection fraction, respectively). A high correlation was found between peak relaxation velocity and peak filling rate (r = 0.792), while no significant correlation was found between thickening and ejection fraction (r = 0.577). Sestamibi parameters were calculated in 15 patients with known or suspected coronary artery disease and compared with those obtained in 10 normal subjects. In regions supplied by stenotic vessels the average values of peak relaxation velocity and thickening were significantly lower than those obtained in control subjects in the corresponding vascular territory. The average regional values of the diastolic parameter were significantly lower than the corresponding normal range also in regions with preserved systolic function, i.e. with thickening values within 1SD from the mean value of normals. In conclusion, from the ECG-gated acquisition of Sestamibi regional diastolic and systolic functional parameter may be derived; this completes the spectrum of information that can be obtained by a single injection of tracer. PMID- 8492001 TI - Preliminary evaluation in humans of Tc-99m-Q3, a new tracer for myocardial perfusion imaging. AB - Trans[99m-Tc-acac2en(TMPP)2]+, where acac2en is N,N'-ethylenebis(acetylacetone iminate) and TMPP is tris-(3 methoxy propyl) phosphine, (shortened Q3) is a new lipophilic Technetium-99m-labelled compound developed for myocardial perfusion imaging. Encouraging data were obtained in the experimental animal. Aim of this study was to perform a preliminary evaluation of Q3 imaging in humans and to compare it with a reference coronary flow tracer such as Tc-99m microspheres. Eight coronary artery disease patients (males, age 58.5 +/- 10 years) were studied. They were injected with 740 MBq of Q3 and single photon emission computed tomography (SPECT) was performed 90 minutes later. After 3 days 740 MBq of Tc-99m microspheres were injected through a pig-tail catheter in the left ventricle (LV), during heart catheterization, and SPECT was acquired 60 minutes later. Q3 images showed a good target/background activity ratio:LV wall/LV cavity = 4.16 +/- 1.2; myocardium/lung = 3.95 +/- 0.52; the related values with microspheres were 6.36 +/- 2.48 (N.S.) and 4.57 +/- 1.07 (N.S.), respectively. Q3 was cleared by the liver and at the moment of SPECT collection the myocardium/liver activity ratio was 1.54 +/- 0.32. The Q3 LV lateral wall/septum activity ratio showed a good correlation with the corresponding microspheres ratio: Q3 ratio = 0.027 + 0.95 microspheres ratio, r = 0.89, SEE = 1.12, p < 0.005. PMID- 8492002 TI - Left atrial thrombi in non-rheumatic atrial fibrillation: assessment of prevalence by transesophageal echocardiography. AB - To determine the prevalence of left atrial thrombus in hospitalized patients with non-rheumatic atrial fibrillation, 48 patients were consecutively studied with single-plane transesophageal echocardiography. There were 23 males (48%) and 25 females (52%). The mean age was 66 +/- 11 years (range 43-87). Thrombus was detected in 13 patients (27%): 11 were confined to the left atrial appendage, 1 to the atrial body and appendage, and 1 to the left upper pulmonary vein. Prevalence of atrial thrombus was not different among those patients with or without previous stroke [4/16 (25%) vs 9/32 (28%), p = NS] or between patients > 65 years and patients < or = 65 years old (p = NS). Atrial thrombus was detected more frequently in patients with reduced left ventricular global systolic function than in those with normal function [7/14 (50%) vs 6/34 (17%), p < 0.05]. In patients with spontaneous contrast echoes in the left atrium, thrombi were visualized more often than in those without spontaneous echoes [10/24 (41%) vs 3/24 (12%), p < 0.05]. The finding of the atrial spontaneous contrast echoes was more frequent among patients with reduced left ventricular global systolic function [11/14 (78%) vs 13/34 (37%), p < 0.02]. We conclude that in hospitalized patients with non-rheumatic atrial fibrillation the prevalence of left atrial thrombus is high. Reduced left ventricular global systolic function identifies a subset of patients at high risk for formation of thrombus in the left atrium. PMID- 8492003 TI - Flow quantitation by radio frequency analysis of contrast echocardiography. AB - Contrast echocardiography has the potential for measuring cardiac output and regional blood flow. However, accurate quantitation is limited both by the use of non-standard contrast agents and by the electronic signal distortion inherent to the echocardiographic instruments. Thus, the aim of this study is to quantify flow by combining a stable contrast agent and a modified echo equipment, able to sample the radio frequency (RF) signal from a region of interest (ROI) in the echo image. The contrast agent SHU-454 (0.8 ml) was bolus injected into an in vitro calf vein, at 23 flow rates (ranging from 376 to 3620 ml/min) but constant volume and pressure. The ROI was placed in the centre of the vein, the RF signal was processed in real time and transferred to a personal computer to generate time-intensity curves. In the absence of recirculation, contrast washout slope and mean transit time (MTT) of curves (1.11-8.52 seconds) yielded excellent correlations with flow: r = 0.93 and 0.95, respectively. To compare the accuracy of RF analysis with that of conventional image processing as to flow quantitation, conventional images were collected in the same flow model by two different scanners: a) the mechanical sector scanner used for RF analysis, and b) a conventional electronic sector scanner. These images were digitized off-line, mean videodensity inside an identical ROI was measured and time-intensity curves were built. MTT by RF was shorter than by videodensitometric analysis of the images generated by the same scanner (p < 0.001). In contrast, MTT by RF was longer than by the conventional scanner (p < 0.001). Significant differences in MTT were also found with changes in the gain setting controls of the conventional scanner. To study the stability of the contrast effect, 6 contrast injections (20 ml) were performed at a constant flow rate during recirculation: the spontaneous decay in RF signal intensity (t1/2 = 64 +/- 8 seconds) was too long to affect MTT significantly. In conclusion, the combination of a stable contrast agent and a modified echocardiographic instrument provides accurate quantitation of flow in an in vitro model; RF analysis is more accurate than conventional processing as to flow quantitation by contrast echocardiography. PMID- 8492004 TI - A review of oxycodone's clinical pharmacokinetics and pharmacodynamics. AB - Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a strong opioid agonist that is available alone or in combination with mild analgesics. It is suitable for oral administration due to high bioavailability (60%), and may also be given intramuscularly, intravenously, subcutaneously, and rectally; it is not recommended for spinal administration. In analgesic potency, oxycodone is comparable to morphine. With the exception of hallucinations, which may occur more rarely after oxycodone than after morphine, the side effects of these drugs are closely related. The abuse potential of oxycodone is equivalent to that of morphine. The usual indications for oxycodone are severe acute postoperative or posttraumatic pain and cancer pain. When oxycodone is administered, the same precautions should be taken as with morphine or other agonist opioids. PMID- 8492005 TI - Management of headaches in children and adolescents. AB - Deciding whether a child's headache is functional or organic is difficult for even the experienced physician. This review examines the diagnosis and management of headache syndromes in children and adolescents. A systematic history and examination together with selected laboratory data will enable the practitioner to establish the correct diagnosis. PMID- 8492006 TI - Headaches in the elderly. AB - Headache prevalence and etiology vary dramatically with age. The prevalence of primary headache disorders, such as migraine and cluster, declines with age, while the prevalence of secondary headache disorders, such as temporal arteritis and mass lesions, increases. In evaluating elderly patients with new onset of headache, a high index of suspicion for organic disease is required. Headache symptomatology also varies with age. For example, migraine may evolve into a pattern of chronic daily headache, or auras may occur in the absence of headache (late-life migraine accompaniments). A careful longitudinal headache history is therefore important. Headache management is also influenced by age. Elderly people are more susceptible to medication side effects and are often treated with several drugs. Medications may cause headaches and drug interactions may complicate therapy. For these reasons, age of onset and duration of illness are critical headache features that guide the subsequent approach to diagnosis and treatment. PMID- 8492007 TI - Sex hormones and headache. AB - A variety of evidence suggests a link between migraine and the female sex hormones. Women with migraine outnumber men by at least a 2:1 ratio and definite patterns of development and attacks are noted at menarche and throughout the period of menses, related to trimester of pregnancy, and again at menopause, although it may also regress. Hormonal replacement with estrogen can exacerbate migraine; oral contraceptives can change the character and frequency of migraine headache. This article will cover approaches to the therapy of hormone-related headaches associated with the menstrual cycle, menopause, and oral contraceptives. PMID- 8492008 TI - [Experimental study on antitumor effect of cisplatin-microcapsule]. AB - CDDP-microcapsule (CDDP-mc) was prepared in the search for method for administering anti-cancer agents and has been examined for its properties, vital reaction and antitumor effect. In the present study, the results of the examination and possibility of application of CDDP-mc are reported. 1) It took 48 hours for CDDP to be released from the microcapsule into saline. 2) CDDP-mc size is 80-200 microns, and it contains 0.645mg of CDDP per mg of microcapsule. It was available as a drug enabling us to introduce a high concentration of CDDP into tumor tissue. 3) The side effects of CDDP-mc on animals (rabbit and rat) were more limited than those of ordinary CDDP solution and slight, especially for intraperitoneal or local injection. Intraarterial infusion of CDDP-mc, however, causes transitory palsy of the treated lower extremity probably due to embolism. 4) Its intraperitoneal administration was much more effective than the ordinary CDDP solution against Yoshida's sarcoma implanted in rats. 5) The subcutaneous administration of CDDP-mc was more effective compared to ordinary solution of CDDP. 6) The above results suggested that CDDP-mc is clinically applicable to the treatment of ovarian cancer and uterine cancer when administered intraperitoneally and locally (intra-tumor). PMID- 8492009 TI - [A quality control for the culture system using endotoxin assays in human in vitro fertilization and embryo transfer]. AB - The purpose of this study is to investigate the effects of endotoxin on human in vitro fertilization and embryo transfers (IVF-ET) and to evaluate a quality control system for a culture medium using endotoxin assays. Before the final water purification (in an ultra-pure water system with a depyrogen filter) of the medium, the sources of water were pre-purified as follows; (I) distillation- >deionization x 2, (II) distillation-->ultra-pure water system or (III) reverse osmosis system. The limulus amebocyte lysate gelation tests (sensitivities of 0.03 and 0.25EU/ml) were used to detect endotoxin in the medium and in pre purified water (pre-water). No pregnancies occurred in the endotoxin-positive medium (endotoxin > or = 0.03EU/ml). The endotoxin-negative medium resulted in a 33.3% pregnancy rate and 13.4% implantation rate. No statistical differences in the implantation rate were found among these methods of pre-purification (I: 12.5%, II: 13.4% and III: 20.0%). Endotoxin was detected in all the pre-water between 0.25 and 4.0EU/ml. The clinical pregnancy rate (36.6%) and the implantation rate (16.9%) in pre-water of endotoxin < 0.25EU/ml were significantly higher than those (10.5% and 5.5%) in pre-water of endotoxin > or = 0.25EU/ml (p < 0.05). We confirmed that a very low concentration of endotoxin disturbed a human embryo implantation. Endotoxin assays, not only in the media, but also in pre-water before final purification are useful as a quality control for the IVF-ET program. PMID- 8492010 TI - [The role of matrix metalloproteinases for premature rupture of the membranes]. AB - In order to investigate the correlation between premature rupture of the membrane (PROM) and chorioamnionitis, the effects of human tumor necrosis factor alpha (TNF alpha) and human interleukin-1 alpha (IL-1) on the production of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and prostaglandin E2 (PGE2) in cultured human chorionic cells, were examined. The results were as follows: 1) TNF alpha enhanced the production of MMPs and PGE2 and suppressed TIMP production. 2) IL-1 stimulated the production of MMPs, TIMP and PGE2. 3) The combination of IL-1 and TNF alpha further augmented IL-1-induced production of MMPs, but IL-1-induced TIMP was suppressed by TNF alpha treatment. 4) At term, remarkable Type I collagenolytic activity was found in amniotic fluid from a patient with PROM complicated chorioamnionitis, whereas no collagenolytic activity was found in normal amniotic fluid. These results suggest that the degradation of extracellular matrix in fetal membranes with intraamniotic infection is caused by MMPs derived from chorionic cells through the inflammatory cytokines released in response to bacterial infection; PGE2 is released, causing uterine contraction. These effects combine to induce PROM. PMID- 8492011 TI - [Development and clinical research of computer aided multivariate pattern analysis system (CAMPAS) OV-1 for diagnosis of ovarian carcinoma]. AB - A computer aided multivariate pattern analysis system (CAMPAS) OV-1, which consisted of 10 discriminant functions based on eight tumor markers including CA125, IAP, TPA, LDH, CRP, CEA, amylase and alkaline phosphatase was developed to effectively diagnose patients with epithelial ovarian carcinoma. One hundred twenty-two patents with epithelial ovarian carcinoma and 215 patients with benign ovarian tumors were examined by using CAMPAS OV-1 retrospectively or prospectively. The clinical significance of CAMPAS OV-1 was compared with CA125 alone, and with a combined assay employing the eight tumor markers used in CAMPAS OV-1. The following results were obtained. 1. When CAMPAS OV-1 was applied to patients in which the value for each tumor marker was used to make the discriminant functions, the sensitivity, specificity and accuracy were 84.5%, 97.5% and 91.3%, respectively. The accuracy of CAMPAS OV-1 (91.3%) was significantly better than those of CA125 (80.0%) and combined assay (74.0%) [p < 0.001]. CAMPAS OV-1 showed relatively better sensitivity (63.3%) than CA125 (50.0%) in patients with stage I disease. Also CAMPAS OV-1 showed relatively better sensitivity (85.7%) than both CA125 (64.3%) and combined assay (78.6%) in patients with mucinous type tumors. Furthermore, the specificity of CAMPAS OV-1 (94.4%) was significantly better than those of CA125 (66.7%) and combined assay (55.6%) in patients with endometrial cysts [p < 0.05]. 2. When CAMPAS OV-1 was applied to the patients prospectively, whose values for each tumor marker were not used to make the discriminant functions, the sensitivity, specificity and accuracy were 88.2%, 83.8% and 85.0% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492012 TI - [Relation between the outcome of IVF-ET and subtle rise in serum progesterone during the follicular phase stimulated with a combination of gonadotropin releasing hormone analog and gonadotropin]. AB - This study was designed to investigate whether the rise in the serum progesterone concentration (1.0 to 2.0ng/ml) (P rise) during the follicular phase occurs in cycles stimulated with gonadotropin-releasing hormone analog (GnRHa) and gonadotropins (hMG and pure FSH), and whether the P rise affects the outcome of IVF-ET. Three hyperstimulation regimens were used for IVF-ET; short regimen (SR): 64 cycles of 44 patients, long regimen (LR): 78 cycles of 46 patients, and pure FSH regimen (PR): 16 cycles of 16 patients. Although serum LH levels did not significantly change during the follicular phase in any of the regimens, a P rise was observed frequently in all the three regimens (26.6% per cycle in SR, 15.4% per cycle in LR, and 18.8% per cycle in PR, respectively). Significantly higher serum E2 levels (p < 0.05) and a greater number of collected oocytes (p < 0.05) but significantly lower rates of mature oocytes (p < 0.05) and fertilization (p < 0.05) were observed in P rise cycles compared to no P rise cycles. Ten of 12 ongoing pregnancies in this study occurred in no P rise cycles. These results suggest that the increasing number of developing follicles related to a high concentration of serum E2 is responsible for the occurrence of P rise irrespective of whether LH is endogenous or exogenous, and that the P rise affects the outcome of IVF-ET. PMID- 8492013 TI - [Clinical evaluation of tumor-associated trypsin inhibitor (TATI) in benign and malignant gynecological tumor]. PMID- 8492014 TI - [Improved technique of Shirodkar's cervical cerclage operation based on the theological surgery]. PMID- 8492015 TI - [Possibility of vertical transmission of hepatitis C virus]. PMID- 8492016 TI - [Three cases of congenital complete A-V block]. PMID- 8492017 TI - [Clinical study for three cases of luteal phase dysphoric disorder--their personality and endocrinological feature]. PMID- 8492018 TI - [Pathophysiology of cardiomyopathies]. PMID- 8492019 TI - [Etiology and classification of cardiomyopathies]. PMID- 8492020 TI - [Genetic and molecular biological aspects on cardiomyopathies]. PMID- 8492021 TI - [Coronary hemodynamics of cardiomyopathies]. PMID- 8492022 TI - [Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy]. PMID- 8492023 TI - [Diagnosis of cardiomyopathies by palpation and physiological findings]. PMID- 8492024 TI - [Differential diagnosis of cardiomyopathies]. PMID- 8492025 TI - [ECG findings of cardiomyopathies]. PMID- 8492026 TI - [Echocardiographic findings of cardiomyopathies]. PMID- 8492027 TI - [Diagnosis of hypertrophic myocardiopathies by ultrafast CT scanner]. PMID- 8492028 TI - [Radioisotope imaging of cardiomyopathies]. PMID- 8492029 TI - [Cardiomyopathies and cardiac sudden death (discussion)]. PMID- 8492030 TI - [A case of Epstein-Barr virus infection with splenic hemorrhage and pleural effusion]. PMID- 8492031 TI - [A case of copper deficiency with various clinical symptoms]. PMID- 8492032 TI - [A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia]. PMID- 8492033 TI - [A case of hemodialysis-induced brain disease with intracranial calcinosis]. PMID- 8492034 TI - [A case of Waldenstrom macroglobulinemia with pulmonary lymphocyte infiltration treated with alpha interferon]. PMID- 8492035 TI - [Helicobacter pylori and gastric mucosa]. PMID- 8492036 TI - [Arrhythmia and catheter ablation]. PMID- 8492037 TI - Comparison of bursting pressure of sutured, stapled and BAR anastomoses. AB - The study was undertaken to compare anastomotic bursting pressure (ABP) of colorectal canine anastomoses using three different anastomotic techniques. Biofragmentable anastomotic ring (BAR), stapled, and sutured colon anastomoses were sequentially placed in each of 48 dogs following division of the colon at three equally spaced sites. Four groups of 12 dogs were sacrificed either on day 0, 3, 7, or 28 and ABP and bursting wall tension were determined. The data revealed that BAR anastomoses have the greatest strength on the day of surgery, sutured anastomoses are the strongest on the third day and all are comparable by the 7th day. Bursting pressures for all groups by day 28 approach normal colonic bursting pressure, with any differences likely to be a reflection of variation in anastomotic fibrosis and other factors. PMID- 8492038 TI - Evaluation of isotope proctography in constipated subjects. AB - Twelve patients with longstanding constipation were examined by isotope proctography. Radio-labelled potato mash was inserted rectally to provoke the urge to defaecate and expulsive manoeuvres were recorded using a Gamma-camera. The method illustrated dynamic alterations in the anorectal angles (ARA) which became more acute on 'squeezing', less so on coughing and more obtuse on straining, and maximally so on evacuation. The pelvic floor (PF) movements were consistently upwards on squeezing, less so on coughing, downwards on straining, and maximally so on evacuation. A useful addition was the measurement of the completeness of evacuation and the time involved. The results were comparable to radiological videoproctography (P < 0.01), but the isotope method gave greater discrimination for both ARA and PF movement changes. It also allowed correlations to be made between the pelvic floor descent (P < 0.05) and anorectal angle changes (P < 0.01) with rectal evacuation. PMID- 8492039 TI - Rectal sensory evoked potentials: an assessment of their clinical value. AB - To assess abnormalities of sensory conduction in anorectal disease we have evaluated peripheral sensory perception and somatosensory evoked potentials produced by rectal stimulation in control subjects and patients with either constipation or idiopathic faecal incontinence. Evoked potentials were also recorded after posterior tibial and dorsal genital nerve stimulation. Rectal sensation was also assessed using electrical stimulation. Reproducible evoked potential recordings after anorectal stimulation were possible in only a minority of subjects and when recorded showed intersubject and intrasubject variation. In the constipated group there was a significant difference in rectal electrical sensation (P < 0.05) from controls. We conclude that peripheral sensory testing demonstrates an abnormality in severe constipation. However, cerebral evoked potentials cannot be reliably recorded after rectal stimulation, and when recorded the latencies are of too broad a range to discriminate between health and disease. This probably relates to the difference between somatic and visceral pathways. PMID- 8492040 TI - Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand sewn? A prospective, multicenter, randomized trial. AB - 440 patients were prospectively enrolled in a randomized, multicenter trial to compare 4 types of manual (84 interrupted end-to-end, 77 continuous end-to-end, 82 interrupted end-to-side, and 91 continuous end-to-side) (polyglycolic derived suture) and 1 type of stapled (106 side-to-side with GIA+TA devices) ileocolonic anastomosis after right hemicolectomy for carcinoma. The trial was designed according to Schwartz' pragmatic formulation. All 5 groups were well-matched, except for a lower rate of intraoperative sepsis in the stapled group (P < 0.02). The main end point was anastomotic leakage detected clinically or by routine sodium diatrizoate enema on the 8-10th postoperative day. Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages (2.8%) than all the other techniques combined (8.3%). In spite of the fact that staples are approximately ten times more expensive, our results suggest performing side-to-side (GIA+TA) mechanical anastomosis after right resection for carcinoma. PMID- 8492041 TI - Outcome of perianal fistulae in Crohn's disease--value of Hughes' pathogenic classification. AB - Applying the Hughes' pathogenic classification of ano-perineal lesions of Crohn's disease, this study was conducted to find out its possible prognostic value in perianal fistulas. Thirty-eight patients with ano-perianal fistulas were included; primary specific lesions (condyloma, cavitating ulcer, fissure) were found in 22 patients (group 1) and were absent in the other 16 patients (group 2). Patients of group 1 underwent more abdominal surgical interventions (G 1: 68%; G 2: 31% - P = 0.05), as well as proctological interventions (G 1: 2.95 operations/patient vs 1.35 in G 2 - P = 0.01). Perfect continence was recorded ultimately in 31.8% patients of G 1 compared to 62.5% of G 2. This study shows the very poor prognosis of ano-perianal fistulas in Crohn's disease. PMID- 8492042 TI - Familial varices of the colon and small bowel. AB - We describe two patients, brother and sister, with identical pathology, whose only clinical presentation was recurrent massive lower digestive tract bleeding. Haemorrhage was due to a complex form of familial venous vascular malformation in the digestive tract, represented by the existence of varices of colon, small intestine and, to a lesser extent, oesophagus and gastric funcus. We have been able to study, examine and treat both patients for 9 and 3 years respectively. PMID- 8492044 TI - The unopened colostomy: a procedure to protect colonic anastomosis. AB - The results of an alternative to the classic diverting lateral colostomy when used to protect a high risk anastomosis are reported. Fourteen out of 122 patients undergoing colonic or colorectal resection had a restoration of intestinal continuity with a proximal closed loop colostomy--of these 11 did not require opening in the immediate post-operative period. These had an uneventful early post-operative course, and the return of the colostomy to the abdominal cavity was performed within 10 days post-operatively, without having been opened. In three cases where local or general complications occurred, the opening of the colonic loop led to the creation of a conventional temporary protective colostomy. This procedure allowed a reduction of the originally planned number of colostomies by 50%. PMID- 8492043 TI - Colorectal cancer in Denmark 1943-1988. AB - Nation-wide incidence rates are presented of colorectal cancer in Denmark from 1943 to 1988. In Denmark notification of malignant and related diseases is mandatory. The percentage of histologically confirmed tumours is now 95. The annual incidence rate of colon cancer in Denmark has been increasing among men and women combined from 684 cases in 1943-47 to 2020 cases in 1988. In the same period the incidence of rectal cancer has been increasing from 762 cases in 1943 47 to 1108 cases in 1988. We analyzed the effects of age, calendar time, and birth cohort with multiplicative Poisson models. We did not find consistent period effects in the models. We suggest the trends in colorectal cancer incidence rates may be due to changes in environmental factors such as dietary habits and in physical activity. Furthermore, we suggest an etiologic distinction between carcinoma of the rectum, the left colon and the right colon. PMID- 8492045 TI - Treatment of anovaginal fistulas with an anocutaneous flap in patients with Crohn's disease. AB - We report on a new and simple operative technique for closure of anovaginal fistulas with an anocutaneous flap in patients with Crohn's disease. From January 1989 till December 1990 this operation was performed in 10 women with Crohn's disease. Seven of the ten patients suffered from Crohn's proctitis. In these patients a protective enterostomy was applied before the operative closure of the fistula. All fistulas healed primarily. Within a median follow up of 18 months (7 24 months) a relapse occurred in 3 patients; two of these were treated successfully with fibrin injection in one case and a further operative closure of the fistula using the same procedure in the second case. In the third patient a seton was placed into the recurrent fistula track, which is still present after 4 weeks. PMID- 8492046 TI - Gastric heterotopic mucosa in the rectum with Helicobacter pylori-like organisms: a rare cause of rectal bleeding. AB - We report the case of a 9-year-old boy who presented with chronic rectal bleeding. On proctosigmoidoscopy, a polypoid elevation in the rectal ampulla measuring 5 x 3 cm was found. Biopsies were reported to show gastric mucosa. The Giemsa stain showed Helicobacter pylori-like organisms. Including our patient, there are now 30 similar cases reported in the medical literature. The usual manifestations of this rare entity are chronic bleeding and rectal pain. In one half of cases there is chronic rectal ulceration. The recommended treatment is transanal surgical resection unless there is rectal peptic ulceration. H2 receptor blockers are then advised. Surgical excision is carried out after healing has taken place. PMID- 8492047 TI - Learning disabilities in the United States: advocacy, science, and the future of the field. AB - This overview offers a perspective on the distinguishing characteristics, past and present, of the LD field in the United States. The discussion focuses on the complex relationships that exist among the social and political forces that have molded the field, advocacy, and research and teaching practices. It emphasizes the compelling need to establish clinical and scientific validation of LD, to preserve the hard-won achievements of advocacy. PMID- 8492048 TI - A brief look at the learning disabilities movement in the United States. PMID- 8492049 TI - Objectivity and emancipation in learning disabilities: holism from the perspective of critical realism. AB - The present article provides a critique of holism (as developed in the writings of Heshusius, Iano, and Poplin) from the point of view of critical realism, primarily as the latter standpoint is explicated in the writing of the British philosopher of science Roy Bhaskar. Whereas the holists have been largely correct in their criticisms of the positivism and scientism that have characterized theory and practice in the learning disabilities field, it is argued that they run the risk of promoting a subjectivist standpoint with its own set of limitations. PMID- 8492050 TI - Open systems as seen on the street and from the fourteenth floor. PMID- 8492051 TI - Providing appropriate education for students with learning disabilities in regular education classrooms. National Joint Committee on Learning Disabilities. AB - This statement was developed by the National Joint Committee on Learning Disabilities (NJCLD). Representatives of the American Speech-Language-Hearing Association (ASHA) were Rhonda S. Work, Chair; Mabel L. Rice; Stan Dublinske, ex officio. Ann L. Carey, vice president for professional and governmental affairs, was the monitoring vice president. Other member organizations of the NJCLD include the Association on Handicapped Student Services Programs in Postsecondary Education; Council for Learning Disabilities; Division for Children with Communication Disorders; Division for Learning Disabilities; International Reading Association; Learning Disabilities Association of America; National Association of School Psychologists; Orton Dyslexia Society. This statement was approved by the ASHA Legislative Council in November 1990 (LC 26-90) [see Note 1]. PMID- 8492052 TI - The psychoeducational characteristics of children with Turner syndrome. AB - Turner syndrome (TS) is a condition that affects 1 in 2,500 females due to a loss of some X chromosome material. It is characterized by a number of common physical features, including short stature, sexual infantilism, and infertility, as well as by specific learning and behavior problems. This article compares abilities, achievement, behavior, and self-esteem in 67 children with TS and 27 nonaffected controls. Results indicate selective impairments in visuospatial and memory areas and significant underachievement in arithmetic, particularly numerical ability, mental calculation, geometry, and reasoning. Learning problems, a major concern for parents, were not being satisfactorily addressed at school. Poor social competence and increased behavior problems, particularly in the area of hyperactivity, were also noted. Although self-esteem was only marginally lower, issues related to poor peer relations were most problematic. PMID- 8492053 TI - Reexamination of sensory integration treatment: a combination of two efficacy studies. AB - Little empirical support exists for the application of sensory integration treatment (SIT) to assist children with learning problems. Treatment efficacy studies are expensive and difficult to carry out, and they have necessarily employed small samples that are inevitably heterogeneous. We have reanalyzed the efficacy of SIT by combining the data from one study involving 29 children in Alberta and a second study involving 67 children in Ontario. The results from each individual study, and now the results from the combined study, lead one to the conclusion that the therapeutic effect of SIT on children with learning deficits is not greater than other, more traditional methods of intervention. PMID- 8492054 TI - Use of IQ criteria for evaluating the uniqueness of the learning disability profile. AB - Beyond predetermined Performance Scale differences, a group of 24 children with learning disabilities having a lower Verbal, higher Performance IQ profile on the WISC-R and 33 slow learners were not found to be otherwise distinguished by their individual WISC-R subtest scores or subtest scatter. The majority of children were males, white, of lower to middle socioeconomic status and ranged in age from 6 to 13 years. PMID- 8492055 TI - A treatment for carpal tunnel syndrome: results of a follow-up study. AB - OBJECTIVE: This study was a follow-up evaluation of carpal tunnel syndrome (CTS) subjects based on objective and subjective measures utilizing a conservative treatment method. It was hypothesized that the CTS individuals would maintain their improvements over the course of a 6-mo period after treatments. DESIGN: The design used was a case control study in which the improvements of the CTS subjects were compared within themselves and with a matched comparison group. The treatments were performed at a private chiropractic clinic, and the objective and subjective measures were independently taken in an industrial engineering laboratory. All CTS subjects were volunteers from a random sample. Forty-three individuals were evaluated at the pretreatment period and in the 6-mo follow-up. Only 22 subjects returned for reevaluation. The treatment duration was not controlled. RESULTS: The results indicate that CTS subjects had maintained improvements in most of the objective measures and pain and distress ratings over the pretreatment level (p < .05) at 6 mo post-treatment. When compared to a matched comparison group, CTS-treated subjects demonstrated no significant differences (p < .05) in grip strength (for females), pinch strength, forearm pronation and supination forces, assembly task performance and pain and distress scores. CONCLUSION: The results of statistical analyses indicate that CTS subjects can be treated and achieve a significant recovery to within normal comparative levels of non-CTS subjects in most subjective and objective measures. PMID- 8492056 TI - Correlates of myoelectric asymmetry detected in low back pain patients using hand held post-style surface electromyography. AB - OBJECTIVE: Paraspinal surface electromyographic (SEMG) scanning, utilizing post style hand-held electrodes, was conducted to determine the usefulness of the technique as an assessment for myoelectric indicators of low back pain (LBP). A secondary objective was to correlate myoelectric abnormalities with other known outcome measures of the manipulable lesion. DESIGN: Blinded SEMG assessments with the patients standing upright, fully flexed and extended at the trunk, and measures of pressure pain thresholds (PPT) were made after four tests administered by another examiner. SETTING: The research was conducted on patients in a private chiropractic practice. PATIENTS: A convenience sample of 10 of the practitioner's most acute LBP patients without neurological deficit were asked to participate and none refused. Six patients without recent LBP volunteered as controls. MAIN OUTCOME MEASURES: Preset myoelectric indicators included: thoracolumbar asymmetry (T-L/A: first seen in an earlier pilot study), loss of flexion/relaxation (F/R) at L3, contralateral responsivity (increased myoelectric activity opposite the side of leg pain) and right/left asymmetry (R-L/A) at L3. RESULTS: Significant differences between groups were seen in T-L/A (p = .04) and R-L/A [data averaged from three postures (p = .04)], and robust group differences were seen in F/R (p = .011 right; p = .026 left). Contralateral responsivity was not significant. Loss of F/R was the only indicator that correlated with diminished PPT (r = .52 right; r = .46 left) and with Oswestry disability (r = .42), and that negatively correlated, as expected, with straight leg raising (r = -.50 right; r = -.74 left). CONCLUSIONS: Results support use of the technique to detect muscle dysfunction related to LBP. Further research of SEMG correlations with measures of the manipulable lesion is warranted. PMID- 8492057 TI - Correlation study on infrared thermography and nerve root signs in lumbar intervertebral disk herniation patient: a short report. AB - OBJECTIVE: To determine whether infrared skin thermography is an objective measurement reflecting the seriousness of nerve root irritation in lumbar disk herniation patients. DESIGN: Quantified nerve root signs by physical examination were collected from the patients along with the infrared skin temperature measurement on the lumbosacral region and posterior part of thighs. A correlation study was applied to observe the relation between the nerve root signs and the skin temperature before a successful conservative treatment (mainly spine manipulation), and between the alteration of nerve root signs and that of skin temperature after the treatment. SETTING: Hospitalized care. PATIENTS: Twenty seven hospitalized samples with computed tomography or magnetic resonance approval were consecutively selected during the latter half of 1990. MAIN OUTCOME MEASURE: Changes in nerve root signs. RESULTS: The temperature difference between a troubled thigh and healthy one is significantly correlated to the score of the nerve root signs before the treatment; and the reduction of temperature difference between two thighs is also significantly correlated with decreasing score of nerve root signs after the treatment. The correlation between the temperature difference on the left and right sides of the lumbosacral region and the nerve root signs before the treatment is insignificant; and the variation of the temperature difference of the same region after the treatment is not correlated with the decreasing score of the nerve root signs. CONCLUSION: Infrared skin thermography of lower extremities might be an objective sign in signaling the soothing process of the nerve root irritation in lumbar disk herniation patients, which may help a doctor in checking the responses of the patient to treatment. PMID- 8492058 TI - A comparison of two modes of cervical exercise in adolescent male athletes. AB - OBJECTIVE: The Saturn-Ring is a new device that claims to increase cervical strength and flexibility. Therefore, the objective was to assess if use of the Saturn-Ring with conventional exercise would increase cervical strength, flexibility and circumference over conventional exercise alone. DESIGN: Subjects were randomly divided into two matched groups and a before/after design utilized. For pretest data, collection was done in a double-blind fashion. During the post test, only the athlete knew the group in which he had participated. SETTING: The entire study was conducted in a high school field house. PARTICIPANTS: Fifty football players randomly chosen from a high school team served as subjects for the study. One subject was randomly selected from the pool of potential players and a matched subject was selected for the second group according to age, height and weight. This continued until both groups had 25 subjects. INTERVENTION: In addition to normal football exercises and practice, the experimental group used the Saturn-Ring five times a week over the 8-wk exercise program. MAIN OUTCOME MEASURES: Cervical strength and flexibility (flexion, extension, right lateral flexion and left lateral flexion) and girth size of the neck were measured before and after an 8-wk exercise program. RESULTS: Both groups showed significant gains in strength, flexibility and neck size. Further testing determined that the post test results for the experimental group were significantly greater than the post test results for the control group for neck sizes and all possible strength and flexibility measurements. CONCLUSIONS: The result of this study indicate that Saturn-Ring exercises in conjunction with conventional exercises will significantly increase cervical strength, flexibility and size over conventional exercises alone. There were several implications for further study: a) replicate the study to single out the effect of the Saturn-Ring alone, b) replicate the study with a broader spectrum of the population and include injured patients and c) research is needed to assess if the use of the Saturn-Ring can decrease the potential for cervical injury. PMID- 8492059 TI - Does the goose really lay golden eggs? A methodological review of Workmen's Compensation studies. AB - OBJECTIVE: To assess the value of workmen's compensation (WC) studies to determine the effectiveness of chiropractic. Therefore, the results of the available WC studies are summarized and the methodological quality of WC studies is discussed. DATA SOURCES: All studies were eligible without time restriction. Studies were identified by a Medline search from 1966 to 1990 (key words: chiropractic, and manipulation-orthopedic in combination with comparative studies, follow-up studies, evaluation studies) by manual examination of the most important chiropractic reference systems (CRAC and Index to Chiropractic Literature), by tracking the reference lists of identified (reviews of) WC studies and by correspondence with researchers. STUDY SELECTION: Studies were regarded as WC studies if by means of databases of WC boards, a comparison was made between claimants treated by chiropractors and those treated by other health care professionals. At least one of the following outcomes should be reported: compensated days, compensation paid or treatment costs. DATA EXTRACTION: Relevant data (authors, year, state, study population, number of patients, days compensated, compensation paid, number of treatments, consultation costs, additional treatment costs and total cost per case) were extracted by one nonblinded observer. The methodological value was reviewed narratively. DATA SYNTHESIS: The retrospective character of WC studies and the use of large WC databases harbor severe methodological problems like incomparability of study groups, absence of information on prognostic indicators, insufficient outcome measures and missing data. The results of older WC studies (before 1980) and the more recent WC studies, which were of better methodological quality, are presented separately. The older studies are in favor of chiropractic. Two of the six more recent WC studies challenge chiropractic effectiveness. CONCLUSIONS: WC studies in general report positive results for chiropractic. Recent results are more ambiguous. Because of the methodological drawbacks identified, WC studies are insufficient to enable a valid study made of chiropractic effectiveness. Therefore, chiropractic (cost-) effectiveness is not yet convincingly proven. More effort should be directed at establishing randomized clinical trials including the question of (cost-) effectiveness. PMID- 8492060 TI - Nutrition as an environmental factor in the etiology of idiopathic scoliosis. AB - OBJECTIVE: The purpose of this review is to examine the evidence implicating poor nutrition as a causative factor in the etiology of idiopathic scoliosis. Interactions between nutrition and genetics and biochemistry are considered. DATA SOURCES: Articles published in American or European journals or conference proceedings from 1955-1990. STUDY SELECTION: Relevant studies or observations published between 1955 and 1990 are included. DATA EXTRACTION: Data presented were selected by independent extraction by two reviewers. DATA SYNTHESIS: There is strong evidence from an animal model for an interaction between poor nutrition and genetics. There are anecdotal data and limited study data for humans. The biochemical mechanisms, explaining the actions of nutritional factors on spinal and paraspinal tissue, are partially known. CONCLUSIONS: There is evidence that poor nutrition may play a role in the etiology of idiopathic scoliosis. This possibility should be examined further in humans. PMID- 8492061 TI - Management of cervical disk syndrome utilizing manipulation under anesthesia. AB - Although there is an abundance of material in the literature regarding manipulation under anesthesia for the lumbar spine, there is little concerning the cervical spine. This article discusses a case of traumatically induced cervical disk syndrome accompanied by degenerative disk and joint disease that resolved after a series of manipulations to the cervical spine under anesthesia. Indications for the procedure are presented as well as a description of the procedure. PMID- 8492062 TI - Aneurysmal bone cyst of the hand. AB - This article discusses a case of an aneurysmal bone cyst in the finger of a male patient. Such tumors are rarely located in the hand. Although rare, an aneurysmal bone cyst is the only benign bone tumor which can extend across a growth plate into the epiphysis. Diagnostic and therapeutic features of the cyst are discussed in this article. PMID- 8492063 TI - Treatment of multiple lumbar disk herniations in an adolescent athlete utilizing flexion distraction and rotational manipulation. AB - An acute case of low back pain in a high school athlete is described. Onset of nonradicular back pain was related to "squat-type" weightlifting in preparation for high school football. Magnetic resonance images demonstrated central posterior disk herniations with thecal sac effacement of the lower three disk levels. Clinical and electrophysiological evaluation revealed no neurological deficits. Flexion distraction and rotational manipulation with adjunctive paraspinal muscle stimulation resulted in early improvement and apparent long term resolution of this patient's symptoms. The effectiveness of flexion distraction and rotational manipulation in reducing subjective symptoms are compared utilizing visual analog pain scales. Literature review of the conservative treatment of lumbar disk herniations is discussed. PMID- 8492064 TI - The effect of manipulation on pain and range of motion in the cervical spine: a pilot study. PMID- 8492065 TI - Compression fractures in patients undergoing spinal manipulative therapy. PMID- 8492066 TI - Quackery vs. accountability in the marketing of chiropractic. PMID- 8492067 TI - Hepatocyte growth factor: another ubiquitous cytokine. PMID- 8492069 TI - Steroidal interactions in the ageing endocrine system: absence of suppression and pathology in reproductive systems of old males from a mixed-sex socially stressful rat colony. AB - A paradigm using chronic social stress and multiple measures of the reproductive system were used to assess changes with ageing in the dynamics of endogenous steroid interactions. The 22- to 24-month-old male rats lived for 8 weeks in one of four types of colony, in groups of the same sex or groups of mixed sex including familiar or unfamiliar old males. Measures of endocrinology (circulating steroid levels), behaviour (exploration and sociosexual responses), physiology (body and organ weights and epididymal sperm count) and histology (adrenal and ventral prostate glands) served as markers of activation of the hypothalamic-pituitary-adrenal (HPA) or hypothalamic-pituitary-testicular (HPT) axes. Old males living under stable conditions as familiar same-sex colonies served as the comparison group. Results indicated clear chronic activation of the HPA axis in the unfamiliar all-male colonies and of the HPT axis in the familiar males from mixed-sex colonies, whereas both steroidal axes were stimulated in colonies of unfamiliar males and females. Findings from aged males under chronic stress suggested that reproductive dysfunction may be limited to situations in which activation of the HPA axis occurs without concurrent stimulation of the HPT axis. Data on steroidal interactions from mixed-sex groups suggested that (1) chronic excitation of the HPA failed to suppress function in the reproductive system of the old males, (2) their stress responses were little affected by chronic HPT activation and (3) there was no evidence for stress-induced pathology, even in the vulnerable prostate gland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492068 TI - Interaction between insulin and thyroid hormone in rat pituitary tumour cells: insulin attenuates tri-iodothyronine-induced growth hormone mRNA levels. AB - Insulin has previously been shown to inhibit basal and stimulated rat GH (rGH) secretion as well as basal GH transcription in rat pituitary cells. The effect of physiological doses of insulin on tri-iodothyronine (T3)-stimulated GH mRNA levels in rat pituitary tumour cells was therefore examined. Insulin (7 nmol/l) suppressed T3-stimulated GH mRNA levels in GC and GH3 rat pituitary tumour cells by 58%. This inhibitory effect of insulin on T3-stimulated GH mRNA levels was already present after 24 h of treatment, and persisted for at least 48 h after insulin treatment was withdrawn. The effect of insulin on GH mRNA was selective, as rat prolactin mRNA was stimulated by insulin and T3 in the same cells. Treatment of cells with cycloheximide (10 mumol/l) did not alter the attenuation of GH mRNA levels by insulin, indicating that the insulin effect is independent of new protein synthesis. When de-novo mRNA synthesis was blocked with actinomycin D (4 micrograms/ml) for up to 7 h, an additional decrease in the relative amount of GH mRNA levels was observed after 24, 48 and 72 h of insulin treatment, indicating that an effect of insulin on GH mRNA stability is likely. The results show that physiological doses of insulin selectively attenuate the stimulatory effect of T3 on GH mRNA levels. This suppressive effect of insulin occurs independently of protein synthesis and is presumably mediated both at a transcriptional and post-transcriptional level. PMID- 8492070 TI - Pro-oestrous-specific role for polyamines in mediating the secretion of prolactin induced by thyrotrophin-releasing hormone in the rat. AB - The activity of ornithine decarboxylase (ODC) in the rat anterior pituitary gland varies during the oestrous cycle, with a rise in activity seen at pro-oestrus. This enzyme, which is rate-limiting for the synthesis of the polyamines, can be specifically and irreversibly blocked by alpha-difluoromethylornithine (DFMO). A previous study showed that when this drug was administered to rats in vivo on the afternoon of pro-oestrus, it suppressed the normal surge in plasma prolactin levels that occurred later that day. The effect of DFMO was associated with reduced levels of putrescine in the anterior pituitary gland, suggesting that ODC activity in the lactotroph might be involved in the prolactin surge. We have examined the effects of DFMO on the secretion of prolactin from anterior pituitary cells, isolated either from male rats or from females at different stages of the oestrous cycle. The drug was found to reduce prolactin secretion stimulated by thyrotrophin-releasing hormone (TRH), but only in cells isolated from pro-oestrous animals and only for 2 days after cell isolation. Basal secretion was unaffected by DFMO. The results imply that ODC is important for TRH stimulated prolactin secretion at pro-oestrus, and it is specific for pro oestrus. The prolactin surge could therefore be influenced by this ODC-dependent effect of TRH: The pro-oestrous-specific response to TRH may be a consequence of the increased ODC activity seen at this time. Alternatively, the increased ODC activity could be a consequence of coupling to TRH receptors, which are known to increase in number at pro-oestrus. PMID- 8492071 TI - Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay. AB - An immunoradiometric assay (IRMA) for the measurement of insulin-like growth factor-II (IGF-II) in human plasma has been developed, optimized and evaluated clinically in normal subjects and patients with disorders of the GH/IGF-I axis. Six monoclonal antibodies (MAbs) to recombinant human IGF-II (rhIGF-II) were produced, all of which had low cross-reactivity with rhIGF-I (< 0.01%) and insulin (< 0.01%). Compatibility of pairs of MAbs was tested in two-site IRMAs using three radioiodinated MAbs and three MAbs linked to Sephacryl S-300 (with separation of bound and free radiolabelled MAb by sucrose layering). Seven pairs of MAbs bound rhIGF-II and the combination of 125I-labelled W3D9 and W2H1 linked to solid phase was selected. The optimized assay had a completion time of 4 h, a minimum detection limit of 30 ng/ml (2.5 standard deviations from the zero standard) and detected a single peak of endogenous IGF-II in normal plasma which co-eluted with rhIGF-II after acid gel chromatography. IGF-II was measured in formic acid/acetone extracts of plasma from 16 normal subjects (mean 685, range 516-1008 micrograms/l), four acromegalic patients (mean 637, range 553-700 micrograms/l), fourteen patients with type-1 diabetes (mean 635, range 247-753 micrograms/l), nine patients with uraemia (mean 423, range 78-850 micrograms/l), and three patients with Laron-type GH insensitivity (75, 35 and 36 micrograms/l). No significant fluctuations were detected between samples obtained hourly from 08.00 to 19.00 h in normal subjects. Low levels of IGF-binding proteins (IGFBPs) remaining in plasma extracts may interfere with the measurement of IGF-II and give rise to falsely elevated IGF-II levels in radioimmunoassays or falsely suppressed levels in IRMAs. Such interference did not occur with the IRMA when used to measure IGF-II in extracts from normal subjects, acromegalic patients and patients with type-1 diabetes, and the addition of excess rhIGF-I in order to displace IGF-II from residual IGFBPs had no effect on IGF-II measurements in these samples. However, levels of IGF-II measured in extracts from patients with Laron-type GH insensitivity and patients with uraemia increased markedly after preincubation with excess rhIGF-I. The accurate measurement of IGF-II by IRMA in extracts from these subjects therefore requires the displacement of IGF-II from IGFBPs prior to assay. We conclude that, in contrast to radioimmunoassays, the two-site IRMA developed here provides a practical, rapid and specific method for the measurement of IGF-II in human plasma. PMID- 8492072 TI - Involvement of inhibin in the regulation of FSH secretion in prepubertal bulls. AB - To investigate the physiological importance of inhibin in the regulation of FSH secretion in prepubertal bulls, animals (6-month-old) were passively immunized against inhibin. Five animals were given an i.v. bolus injection of 50 ml inhibin antiserum raised against bovine 32 kDa inhibin in a castrated male goat, and four bulls were given the same amount of castrated male goat serum (control serum) as controls. Treatment with the inhibin antiserum resulted in a marked increase (P < 0.01) in plasma concentrations of FSH within 12 h compared with control animals, and FSH levels in immunized animals remained high until 168 h after the injection. Concentrations of plasma LH and testosterone in the immunized animals were not different from those in the control animals. The present findings provide strong evidence that inhibin plays an important role in the inhibitory regulation of FSH secretion in prepubertal bulls. PMID- 8492073 TI - The early postnatal development of the murine mandibular condyle is regulated by endogenous insulin-like growth factor-I. AB - Skeletal growth during the early postnatal period is thought to be GH independent, and is probably regulated by intrinsic growth factors. We studied the involvement of locally produced insulin like growth factor-I (IGF-I) in the growth of the neonatal mandibular condyle. Immunofluorescence studies revealed intense staining with antibodies to IGF-I in the mandibular condyle of 2-day-old ICR mice. We have also shown that these mandibular condyles contain specific high affinity binding sites (Kd = 0.157 nmol/l) for IGF-I (427 fmol/mg). Autoradiographical studies of iodinated IGF-I revealed that the distribution of the receptors for IGF-I was parallel to that of IGF-I production, mainly in the younger zones of the condyle, namely the chondroprogenitor and the chondroblast cell layers. Immunoinhibition of IGF-I resulted in an almost complete inhibition (-91%) of thymidine incorporation into DNA, as well as in marked degenerative changes in the morphological appearance of the condyle. Our studies support the hypothesis that early postnatal growth is dependent on the paracrine activity of endogenous GH-independent IGF-I. PMID- 8492074 TI - Norethindrone acetate only partially protects the skeleton of rats treated with the LHRH agonist buserelin from oestrogen-deficiency osteopaenia. AB - In women with endometriosis there is concern that therapeutic use of LH-releasing hormone (LHRH) analogues, to lower ovarian oestrogen production and control endometrial hyperplasia, leads to unwanted oestrogen-deficiency bone loss. We have developed an animal model of this LHRH-mediated oestrogen-deficiency bone loss in the rat, using buserelin. The aim was to use this model to determine whether the progestogen, norethindrone acetate, could counter oestrogen deficiency bone loss associated with prolonged treatment with the LHRH agonist buserelin. Four groups of animals which had their bones labelled with 45Ca were studied for 4 weeks: group A, control; group B, buserelin treated; group C, norethindrone acetate treated; group D, norethindrone acetate+buserelin treated. Buserelin was given daily (19.2 pmol/kg body wt); norethindrone was given orally three times/week (1.47 mumol/kg body wt). Bone resorption was monitored by measuring the urinary excretion of hydroxyproline and 45Ca and bone 45Ca content. Buserelin-treated rats developed similarly depressed plasma oestradiol-17 beta values in the presence and absence of progestogen, and both groups given buserelin had significantly smaller uteri than controls or rats given norethindrone without buserelin. However, norethindrone did not prevent buserelin mediated increases in bone resorption. At the end of the study total body calcium values (mean +/- S.D.) in the four groups were (mg) respectively; 2594 +/- 123; 2260 +/- 92 (P < 0.001 compared with controls); 2616 +/- 221; 2415 +/- 130 (P < 0.02 compared with controls). Rats given norethindrone and buserelin in combination had higher values (P < 0.02) than animals given buserelin alone, but significantly less total body calcium than controls (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492075 TI - Pulsatile prolactin secretory patterns throughout the oestrous cycle in the rat. AB - Prolactin secretion throughout the oestrous cycle in the rat remains at a low level and fairly constant, with the exception of the surge at pro-oestrus. The present study was designed to characterize possible changes in pulsatile patterns of prolactin during the oestrous cycle of the adult female rat. Mean values of prolactin increased from dioestrus-2 to pro-oestrus and then decreased to the values found at dioestrus-1. The number of peaks remained fairly constant in any phase of the oestrous cycle. The absolute amplitude of the peaks increased numerically but was not statistically significant from dioestrus-2 to pro-oestrus then decreasing until dioestrus-1. No changes in the relative amplitude or duration of the peaks throughout the oestrous cycle were detected. The results indicated that there is a similar pulsatile pattern of prolactin at any stage of the oestrous cycle, when samples were obtained during the morning. PMID- 8492077 TI - Isolation of FSH from bovine pituitary glands. AB - An improved method is described for the isolation of FSH from bovine pituitary glands. The purification procedure consisted of an initial ammonium sulphate precipitation step followed by triazine-dye chromatography, immobilized metal affinity chromatography, high-performance anion-exchange chromatography and gel filtration. Three highly purified bovine FSH preparations (designated bFSH-A, -B and -C) were obtained, giving yields of approximately 5.7 mg FSH/kg bovine pituitary glands (wet weight), with specific radioreceptor activities for bFSH-A, -B and -C of 61, 25 and 29 units (NIH-FSH-S1)/mg protein respectively. The corresponding biological activities were 217 (bFSH-A), 62 (bFSH-B) and 86 (bFSH C) units/mg, as measured by an FSH in-vitro bioassay. LH levels were found to be < 1% (w/w) as determined by an LH in-vitro bioassay. SDS-PAGE of these bFSH preparations under reducing conditions in 16% polyacrylamide gels showed two major silver-staining bands of apparent molecular masses 19.5 kDa and 15.8 kDa. Their amino acid compositions were in close agreement with the expected composition, based on the bFSH cDNA sequence and results reported by other investigators. N-terminal sequencing of the bFSH-A preparation yielded two major sequences consistent with alpha- and beta-subunits, and a third minor (< 20%) sequence consistent with the alpha-subunit clipped at amino acid residue 6. It was concluded that the bFSH purification procedure reported here is a rapid method which produces bFSH in high yield and high purity, with radioreceptor and in-vitro specific activities comparable with those previously reported by other investigators. PMID- 8492076 TI - Opioids and testicular activity in the frog, Rana esculenta. AB - The presence and activity of brain, pituitary and testicular beta-endorphin (beta EP)-like material have been studied in the frog, Rana esculenta, using reverse phase high-pressure liquid chromatography, coupled with radioimmunoassay and immunocytochemistry. In-vivo and in-vitro treatments with naltrexone were carried out to assess the putative physiological activity of opioid peptides. beta-EP(1 31) and (1-27), together with their acetylated forms, have been identified in brain, pituitary and testis. In particular, beta-EP(1-31) concentrations peaked during July in the brain and pituitary, whilst in testes maximum concentrations were found in April and November. beta-EP immunoreactivity was present in the brain within the nucleus preopticus and nucleus infundibularis ventralis while positive fibres in the retrochiasmatic regions projected to the median eminence. In the testis, interstitial cells, canaliculi of the efferent system, spermatogonia and spermatocytes showed positive immunostaining for beta-EP. In intact animals, naltrexone treatment increased plasma and testicular androgen levels and this effect was confirmed in in-vitro incubations of minced testes. Naltrexone also induced a significant increase in germ cell degeneration. Our results indicated that an opioid system modulates the hypothalamus-pituitary gonadal axis in the frog, Rana esculenta and, for the first time, we have shown that the testicular activity of a non-mammalian species may be regulated by opiates locally. PMID- 8492078 TI - Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats. AB - Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80 81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492079 TI - Arachidonic acid as a second messenger in glucose-induced insulin secretion from pancreatic beta-cells. PMID- 8492080 TI - Growth hormone receptor gene expression in sex-linked dwarf Leghorn chickens: evidence against a gene deletion. AB - GH receptor (GHR) mRNA has been identified in peripheral (liver and muscle) and central (brain and hypothalamus) tissues of sex-linked dwarf (SLD) Leghorn chickens. Total RNA was extracted from the tissues of immature (1 week, 4 week), pubertal (16 week) and adult (> 24 weeks) SLD and K (the normally growing strain) Leghorn chickens. In both groups and all tissues, an mRNA moiety of 4.4 kb hybridized with cRNA probes derived from the rabbit hepatic GHR sequence. An additional low-abundance transcript of 2.8 kb was also identified in some tissues. An age-related increase in expression was observed in K and SLD hepatic GHR mRNA, suggesting normal regulation of SLD GHR gene transcription. Amplification of cDNA from K and SLD tissues in the presence of oligonucleotide primers coding for the intracellular or extracellular domains of the chicken GHR generated electrophoretically separable fragments of expected size. Restriction enzyme digestion of the products with EcoRI, BstNI, HaeIII, NcoI or BamHI produced smaller moieties of expected sizes in both strains. These results demonstrate that, in contrast to broiler SLDs, a GHR gene deletion is not responsible for the GHR dysfunction in Leghorn SLDs. Although the actual defect in GHR gene expression in SLD Leghorns remains to be identified, this study demonstrates that sex-linked dwarfism, like Laron dwarfism, is due to a heterogeneity of lesions. PMID- 8492081 TI - Activin A inhibits cell-cycle progression induced by insulin-like growth factor-I in Balb/c 3T3 cells. AB - The present study was carried out to examine the effect of activin A on cell cycle progression induced by insulin-like growth factor-I (IGF-I) in Balb/c 3T3 cells. When activin A was added together with IGF-I to competent cells primed with epidermal growth factor (primed competent cells), both [3H]thymidine incorporation and nuclear labelling induced by IGF-I were inhibited. The inhibition was concentration-dependent and the maximum inhibition was obtained with 1 nmol activin A/1. To ascertain the time in which activin A exerted its inhibitory action, we divided 12 h, the time required for primed competent cells to progress towards the S phase, into four periods and activin A was added during each of the four periods. It was effective when added during either the second (3 to 6 h) or the third period (6 to 9 h) but it did not affect cell-cycle progression when added during the first (0 to 3 h) or the last period (9 to 12 h). We then examined whether activin A affected intracellular events elicited by IGF-I. It did not affect either autophosphorylation of the IGF-I receptor or calcium entry induced by IGF-I. Likewise, it did not cause any change in the radioactivity of 1,2-diacylglycerol (DAG) in cells prelabelled with [3H]myristate while the increase in the mass of DAG induced by IGF-I was markedly reduced by activin A. The dose-response relationship for the activin A-mediated reduction of DAG mass correlated well with th at for the activin A-mediated reduction of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492082 TI - Effects of cytochalasin B on calcium transport by 1,25(OH)2D3- or PTH-treated chick embryonic yolk sac in vitro and in vivo. AB - The present study was done to elucidate the mechanism(s) by which calcium is taken up or transported across the yolk sac membrane of the embryonic chick. We examined the effect of various inhibitors or experimental conditions on the uptake of calcium in vitro. Treatment with ouabain, verapamil, antimycin A and calcium ionophore A23187; substitution of choline for sodium or potassium in the buffer; or incubation of the tissue at 0 degree C had no significant effect on calcium uptake by the yolk sac membrane. Dinitrophenol (DNP) and lanthanum chloride (LaCl2) reduced 45Ca uptake from day 6 and 9 embryos by 15% and 30%, respectively. Cytochalasin B decreased the uptake of 45Ca in yolk sac membrane disks of day 6 embryos, but not in older embryos. The effects of cytochalasin B were explored further in embryos pretreated with either 1,25(OH)2D3 or PTH, both of which enhance calcium uptake. Cytochalasin B decreased calcium uptake in 9-day and 12-day vitamin D-treated embryos to about 60% of their hormone-enhanced level and also decreased PTH-stimulated 45Ca uptake into yolk sac disks by about 50% in embryos of all age groups tested. We also examined the effect of cytochalasin B on 45Ca transport across the yolk sac membrane in vivo. Cytochalasin B did not affect this transport in control (vehicle-treated) embryos. However, it significantly decreased the enhanced in vivo 45Ca transport in day-9 and -12 vitamin D-treated embryos approximately 30% and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492083 TI - Ectoderm promotes differentiation of the presumptive ventral mesoderm in early gastrulae of Bufo arenarum. AB - Cultures of both isolated and conjugated explants from early gastrulae of Bufo arenarum were prepared for a study of the development of ventral mesoderm. Only combinations including components of the deep ventral marginal zone and the animal pole successfully differentiated into blood cells (erythrocytes). Histological studies indicated that, while prospective mesodermal cells constituted the only source of such cells, prospective ectodermal cells provided the necessary stimulus for this kind of differentiation. Differentiated cultures, in which the tracer of cell-lineage fluorescein dextran amine was used to label these components, confirmed the above conclusions. These findings are discussed in the context of current concepts about the formation of mesoderm. PMID- 8492084 TI - Recovery of viability in triploid hybrids between Japanese and European water frogs, and their reproductive capacity. AB - Diploid and triploid hybrids, consisting of the various combinations of chromosome set and cytoplasm between Rana nigromaculata and Rana lessonae, were generated in order to study their viability and reproductive capacity. Reciprocal diploid hybrids and allotriploids, which had two lessonae genomes and one nigromaculata genome in nigromaculata cytoplasm, all died without closing their neural folds. Allotriploids, which had two nigromaculata genomes and one lessonae genome in nigromaculata cytoplasm, all grew into healthy mature males in 12.4% (21 frogs) of zygotes. Following the elimination of lessonae chromosomes, ten of these males produced many spermatozoa containing a haploid set of nigromaculata chromosomes. Other allotriploids, which had either one nigromaculata genome and two lessonae genomes or two nigromaculata genomes and one lessonae genome in lessonae cytoplasm, exhibited slightly improved viability. PMID- 8492085 TI - Specificity of binding of zona pellucida glycoproteins to sperm proacrosin and related proteins. AB - A major regulatory site for species specificity of fertilization in mammals lies at the level of sperm binding to the zona pellucida. This implies a high degree of complementarity between gamete receptor molecules. One putative receptor molecule on spermatozoa is proacrosin/acrosin which binds to zona pellucida glycoproteins (ZPGPs) non-enzymically and with high affinity. The mechanism of recognition involves polysulphate groups in a particular stereochemical orientation and it has been suggested that this may contribute to species specificity of sperm-egg binding. In the present work this hypothesis has been tested by challenging 125I-labelled ZPGPs from pig, cow, and hamster eggs to recognize heterologous sperm proacrosins as well as a variety of sequence-related and unrelated proteins. Results show that pig and cow 125I-ZPGPs bind readily to boar, ram, and bull proacrosin but do not recognize guinea-pig proacrosin or any of the polysulphate binding proteins from rat, hamster, or mouse spermatozoa. Hamster 125I-ZPGPs also recognise boar, ram, and bull proacrosin as well as a range of unidentified proteins in pH3 extracts of hamster, rat, and mouse spermatozoa. The binding of ZPGPs to a variety of proteins not related to proacrosin is strongest to those with a high content of basic residues (i.e., pI > 8.5), although the secondary folding of the target protein is of major importance as boar proacrosin (pI 6.75) has the highest binding capacity of all proteins tested. Cross-reaction of ZPGP probes was not observed to guinea-pig proacrosin, suggesting that in this species the conformation of the protein is different to other sperm proacrosins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492086 TI - Effects of epidermal growth factor, insulin-like growth factor-I, and dialyzed porcine follicular fluid on porcine oocyte maturation in vitro. AB - Undefined follicular factors that may influence nuclear maturation and/or cytoplasmic maturation are required during in vitro maturation of pig oocytes. Epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and dialysed porcine follicular fluid (dpFF) were evaluated for their effects on porcine oocyte nuclear maturation in vitro. In Experiment I, eight different maturation media were made in a split-plot factorial design with dpFF (0% vs. 10% v/v dialyzed pFF) as the whole plot component, and EGF (0.0 vs. 50 ng/ml) and/or IGF I (0.0 vs. 100 ng/ml) as the factorial subplot component. Experiment II was a complete factorial design with dpFF and EGF. Pig follicular granulosa-cumulus oocyte complexes (GCOC) were obtained from slaughterhouse ovaries, washed, and cultured at 38.5 degrees C in a humidified incubator with 5% CO2 in air for 42 h. Following culture, GCOC were mechanically stripped of granulosa-cumulus cells and evaluated for nuclear maturation by light microscopy. In Experiment I, the percentage of Metaphase II oocytes for control, IGF-I, EGF, and IGF-I+EGF treatments without pFF were 50.7%, 52.6%, 80.9%, and 84.3% (control and IGF-I groups significantly less, P < .001). The same treatments in the presence of pFF were similar and high (84.2, 84.9, 82.1, and 86.8%, respectively). Experiment II gave similar results. These results demonstrate that EGF, in the absence of pFF, promotes a similar level of oocyte nuclear maturation as does pFF alone or pFF with EGF and/or IGF-I. IGF-I does not appear to influence nuclear maturation of GCOC. PMID- 8492087 TI - Biological activities of p53 mutants in Burkitt's lymphoma cells. AB - Wild-type human p53 and a series of p53 point mutants isolated from Burkitt's lymphoma (BL) cell lines were tested for their ability to inhibit DNA synthesis in a p53-negative BL cell line and to bind and be degraded by the human papillomavirus type 16 E6 protein. All the mutants lost the wild-type ability to inhibit DNA synthesis, demonstrating that they are all functionally altered. Binding to E6 and consequent degradation of the p53 mutants frequently correlated with changed suppressor properties in BL cells. PMID- 8492088 TI - Identification of regional variants of the rabies virus within the Canadian province of Ontario. AB - Although rabies outbreaks in most parts of the world tend to be host species specific the rabies currently enzootic in the Canadian province of Ontario is hosted by two wildlife species, the red fox and the striped skunk. Previous studies employing monoclonal antibody panels failed to identify any host-specific differences in Ontario rabies virus street isolates, but certain observations suggested the existence of more than one viral strain in terrestrial mammals of this region. The extent of variation of the rabies virus circulating within this region has been re-examined using molecular biology techniques. The N gene of several independent isolates was amplified using PCR and the resulting products were compared by restriction enzyme analysis and, in some cases, by DNA sequencing. This analysis confirmed that there was indeed no host-specific variation in the portion of the viral genome under study but there were, however, very clear and consistent differences in the virus from distinct geographical regions. PMID- 8492089 TI - Neuraminidase augments Fc gamma receptor II-mediated antibody-dependent enhancement of dengue virus infection. AB - Antibody-dependent enhancement (ADE) of dengue virus infection occurs when neutralizing antibodies at sub-neutralizing concentrations or non-neutralizing antibodies form complexes with the virus. These virus-antibody complexes can then attach to a Fc gamma receptor-bearing cell, via the Fc portion of the immunoglobulin, resulting in an increased number of infected cells. ADE may be responsible in part for the most severe clinical manifestations of dengue virus infection which include haemorrhage and shock. Three classes of human Fc gamma receptors exist, Fc gamma RI, Fc gamma RII and Fc gamma RIII. In this study, we examined the effects of neuraminidase on ADE of dengue virus infection mediated by the low-affinity Fc gamma RII. K562 cells, which express only Fc gamma RII, treated with neuraminidase resulted in augmentation of ADE of dengue virus infection by human anti-dengue antibodies. This augmented ADE of infection could be blocked by anti-Fc gamma RII monoclonal antibody IV.3. Incubation of neuraminidase-treated K562 cells with IgG-coated human red blood cells resulted in an increase in the percentage of rosette formations compared with the untreated K562 cells. A bispecific antibody directed against Fc gamma RII and dengue virus (IV.3 x 2H2) enhanced virus infection. Neuraminidase also augmented ADE mediated by this antibody, but to a much lesser degree (by 50%) compared with that seen using conventional human anti-dengue antibody (by 200 to 300%). Fluorescence-activated cell sorting analysis of neuraminidase-treated K562 cells showed that the number of Fc gamma RII-specific antibodies that bind to Fc gamma RII increases by 15 to 20% after treatment with neuraminidase. These results indicate that neuraminidase augments ADE of dengue virus infection and that the augmented ADE is mediated through Fc gamma RII. PMID- 8492090 TI - Sequence variation in the env gene of simian immunodeficiency virus recovered from immunized macaques is predominantly in the V1 region. AB - Three cynomolgus macaques were immunized with recombinant envelope protein preparations derived from simian immunodeficiency virus (SIV). Although humoral and cellular responses were elicited by the immunization regime, all macaques became infected upon challenge with 10 MID50 of the 11/88 virus challenge stock of SIVmac251-32H. The polymerase chain reaction was used to amplify proviral SIV gp120 sequences present in the blood of both immunized and control macaques at 2 months post-infection. A comparison of the predominant sequences found in the region from V2 to V5 of gp120 failed to differentiate provirus recovered from either immunized or control animals. A detailed investigation of sequences obtained from the hypervariable V1 region identified a mixture of sequences in both immunized and control macaques. Some sequences were identical to those previously detected in the virus challenge stock, whereas others had not been detected previously. Phenogram analysis of the new V1 sequences found in immunized animals revealed that they were quite distinct from those from the virus challenge stock and that they included alterations to potential N-linked glycosylation sites. In contrast, new sequence variants recovered from the control animals were closely related to sequences from the virus challenge stock. The difference in diversity of new V1 sequences recovered from immunized and control macaques was highly significant (P < 0.001). Thus, the presence of pre existing immune responses to SIV envelope protein is associated with greater genetic change in the V1 region of gp120. These data are discussed in relation to the epitopes of SIV gp120 that may confer protection from in vivo challenge. PMID- 8492091 TI - Identification of the gene encoding the major capsid protein of insect iridescent virus type 6 by polymerase chain reaction. AB - The gene encoding the major capsid protein of Chilo iridescent virus (CIV) has been identified by PCR using oligonucleotide primers corresponding to different regions of the major capsid proteins of Tipula iridescent virus (TIV) and iridescent virus 22 (IV22). A DNA fragment of 0.5 kbp was amplified using two oligonucleotide primers corresponding to the amino acid positions 146 to 153 and 304 to 313 of the major capsid protein of TIV, respectively. The radioactively labelled DNA fragment derived from PCR was hybridized to a CIV gene library. This analysis revealed that only the EcoRI CIV DNA fragment X [2.85 kbp; 0.589 to 0.603 viral map units (m.u.)] hybridized to the amplified DNA fragment. An RNA transcript of about 1.5 kb was identified when the PCR product was used as a hybridization probe. The same RNA transcript was detected when the EcoRI fragments X and Q (5.9 kbp; 0.603 to 0.631 viral m.u.) were used as probes. This indicates that the expected gene is located within map coordinates 0.589 to 0.631 and harbours part of the DNA sequences of fragments Q and X. The analysis of the DNA sequences of this particular region of the CIV genome revealed the presence of one open reding frame of 1401 bp. The DNA sequences of this region encode a protein of 467 amino acid residues with an M(r) of 51.4K. A high degree (64.7%) of amino acid sequence identity was detected between the major capsid protein of TIV and/or IV22 and the amino acid composition of the identified CIV protein. PMID- 8492092 TI - Characterization of potyviruses from tulip and lily which cause flower-breaking. AB - Five viruses causing colour-breaking of tulip flowers were isolated from tulips and lilies. Tulip-breaking virus (TBV), tulip top-breaking virus (TTBV), tulip band-breaking virus, Rembrandt tulip-breaking virus and lily mottle virus were all characterized as potyviruses by serology and potyvirus-specific PCR. Sequence analysis of amplified DNA fragments spanning a conserved area of the coat protein cistron of potyviruses was performed in order to classify the isolates as distinct viruses or strains. It appears that all tulip-breaking viruses are distinct viruses and TTBV was found to be strain-related to turnip mosaic virus. PMID- 8492093 TI - Cauliflower mosaic virus 35S promoter-controlled DNA copies of cowpea mosaic virus RNAs are infectious on plants. AB - Clones have been constructed that contain full-length cDNA copies of cowpea mosaic virus RNA1 and RNA2, downstream of the cauliflower mosaic virus 35S promoter. The clones, when linearized downstream of the viral sequences, give rise to cowpea mosaic virus-like symptoms when inoculated onto cowpea plants. Viral RNA and virions can be detected in the inoculated plants, demonstrating that the clones are directly infectious. PMID- 8492094 TI - Site-directed mutagenesis of a potyvirus coat protein and its assembly in Escherichia coli. AB - Multiple copies of the Johnsongrass mosaic virus coat protein synthesized in Escherichia coli can readily assemble to form potyvirus-like particles. This E. coli expression system has been used to identify some of the key amino acid residues, within the core region of the coat protein, required for assembly. The two charged residues R194 and D238 previously proposed theoretically to be involved as a pair in the construction of a salt bridge crucial for the assembly process were targeted for site-directed mutagenesis. The results from our experiments suggest that the two residues are required for the assembly process but are not necessarily involved as a pair in a common salt bridge. PMID- 8492095 TI - Inhibition of in vitro cotranslational disassembly of tobacco mosaic virus by monoclonal antibodies to the viral coat protein. AB - It has been shown by others that translation of tobacco mosaic virus (TMV) RNA may begin before uncoating of particles is complete. We provide evidence that this cotranslational disassembly can be inhibited by incubating TMV treated at pH 8 with certain monoclonal antibodies (MAbs) specific for TMV coat protein. The most efficient inhibition was achieved by incubation with some anti-metatope MAbs known to bind to the TMV extremity that becomes disassembled first and contains the 5' end of the RNA, as well as with some anti-cryptotope MAbs that bind only to dissociated coat protein subunits. PMID- 8492096 TI - Wild-type coat protein gene of tobacco mosaic virus mutant Ni 2519. AB - Tobacco mosaic virus mutant Ni 2519 has a selected temperature-sensitive defect in the spreading of local lesions, and additional reported defects in virus assembly and in host range. Here we show that the temperature-sensitive local lesion-spreading defect (which maps in the assembly origin within the gene encoding protein p30) is probably independent of mutations in the pseudoassembly origin or of host range defects resulting from other mutations in the coat protein. One new host range mutant has been isolated. PMID- 8492097 TI - The 5' end generated in the in vitro self-cleavage reaction of avocado sunblotch viroid RNAs is present in naturally occurring linear viroid molecules. AB - The 5' termini of linear forms of avocado sunblotch viroid (ASBVd) isolated from infected tissue have been determined by primer extension analyses. According to the different termini identified, four main populations of linear viroid molecules were found. One of them had the same 5' end as the one produced in the in vitro self-cleavage reaction of ASBVd dimeric transcripts mediated by a hammerhead structure, suggesting a possible involvement of this in vitro reaction in the in vivo replication mechanism of ASBVd. PMID- 8492098 TI - Sequence determination of the P gene of simian virus 41: presence of irregular deletions near the RNA-editing sites of paramyxoviruses. AB - The complete nucleotide sequence of the P gene of simian virus 41 (SV41) was determined. The gene was found to be 1406 nucleotides long and to contain a relatively small open reading frame encoding a cysteine-rich V protein with a calculated M(r) of 24076. We have demonstrated that RNA-editing events occur in SV41 P gene transcripts and that the ratio of edited mRNAs to faithfully copied mRNA (P-mRNA:V-mRNA) is about 1:5 at either 24 or 40 h post-infection. The mRNA with two G insertions was capable of encoding a P protein of 395 amino acids with a predicted M(r) of 41,992. A kinetic study of P and V proteins by Western blot analysis showed that in virus-infected cells the amounts of both proteins were almost equal although the V-mRNA was considerably more abundant than the P-mRNA. Alignment of the SV41 P and V proteins with those of nine other paramyxoviruses demonstrated that irregular gaps were present around the RNA-editing sites. PMID- 8492099 TI - The Jeryl Lynn vaccine strain of mumps virus is a mixture of two distinct isolates. AB - Sequence analysis of the region of the mumps virus genome encoding the putative small hydrophobic protein gene confirms that it is a highly variable region. Jeryl Lynn, the mumps vaccine strain used in the U.K., is shown to be a mixture of two closely related viruses, both probably of American origin. PMID- 8492100 TI - Nucleotide sequence of the envelope protein of a Turkish isolate of tick-borne encephalitis (TBE) virus is distinct from other viruses of the TBE virus complex. AB - Turkish tick-borne encephalitis (TTE) virus causes an acute form of meningoencephalomyelitis in sheep in the north-western region of Turkey. The clinical syndrome resembles louping ill (LI) and the viruses responsible for both LI and TTE are members of the tick-borne encephalitis (TBE) complex of the Flaviviridae. The envelope protein gene of TTE virus was reverse-transcribed, amplified, cloned and sequenced. Alignment of the resultant sequence with those from other viruses of the TBE complex reveals that TTE virus is more closely related, at both nucleotide and amino acid levels (84.6% and 96% respectively), to the Central European (CEE) subtype of the TBE virus, usually associated with human disease. The relationship with LI virus is more distant (83% and 93.5% respectively). These studies support the assertion that the ovine encephalomyelitis found in Turkey is caused by a virus that is genetically distinct from known strains of both LI and CEE viruses and from a number of other known viruses of the TBE complex. PMID- 8492101 TI - Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection. AB - Eleven patients with chronic hepatitis D virus (HDV) infection who had chronic active hepatitis and HDV antigen on liver biopsy were randomised in a crossover therapeutic trial of interferon-alpha 2b vs. no therapy. Nine patients had a history of intravenous drug use (drug free > 6 months before therapy), 8 had histological evidence of cirrhosis, and 7 out of 10 tested were found to be seropositive for antibody to hepatitis C virus (HCV). Six patients were randomised to receive interferon-alpha 2b therapy for 1 year, and 5 patients received no therapy for 1 year followed by the same regime of interferon-alpha 2b treatment. All patients with a history of intravenous drug use found self injection stressful, 3 patients restarted using illicit drugs, and 2 patients with active cirrhosis developed severe thrombocytopenia during therapy and treatment was stopped in these patients. Of the 6 patients who completed at least 11 months of treatment, 4 lost serum hepatitis B surface antigen (HBsAg) with 3 developing antibody to HBsAg and one patient completing treatment. Among the 6 patients who had posttreatment liver biopsy, 5 showed an improvement in liver histology (3 of them lost serum HBsAg). These results provide further evidence that interferon-alpha is beneficial in chronic HDV infection although the psychological stress associated with the treatment, especially in patients with a previous history of intravenous drug use, is not inconceivable. PMID- 8492102 TI - Correlation of HBeAg/anti-HBe, ALT levels, and HBV DNA PCR results in HBsAg positive patients. AB - A highly sensitive polymerase chain reaction (PCR) was used to analyse serum samples from HBsAg-positive patients in Sweden. Forty-two chronic carriers were tested, five of whom were of Swedish origin. Of the total, there were 13 HBeAg positive and 27 anti-HBe-positive patients, while 1 patient was negative for both HBeAg and anti-HBe and one was positive for both markers. Nine of the 13 HBeAg positive carriers and only 7 of the 27 anti-HBe-positive carriers had elevated alanine transaminase (ALT) levels (P = 0.01). Two PCR tests of marginally different sensitivity were used on all patient samples. All 13 HBeAg-positive patients and the patients with and lacking both HBeAg and anti-HBe markers, respectively, were positive in both PCR tests. One HBeAg-positive patient was shown to shed hepatitis B virus (HBV) DNA in both saliva and urine. Twelve of the 27 anti-HBe-positive carriers, 6 of whom had elevated ALT levels, were PCR positive. The remaining 15 had no evidence of HBV DNA and all but 1 had normal ALT levels. A positive PCR result was more common in those anti-HBe-positive patients with elevated ALT levels (P < 0.02). The precore gene from 18 samples was sequenced and, with a few exceptions, showed a high degree of conservation. We suggest that in the absence of optimal tests for infectivity of serum from HBsAg-positive patients, and until PCR becomes more widely available, all anti HBe-positive patients with elevated ALT levels be considered highly infectious. PMID- 8492103 TI - Prevalence, infectivity, and risk factor analysis of hepatitis C virus infection in prostitutes. AB - A population of 622 prostitutes in Taiwan was tested for antibodies to the hepatitis C virus (anti-HCV) using a synthetic peptide assay composed of representative determinants from capsid and nonstructural (NS) viral proteins. Seventy-four (12%) were positive and the remaining 548 (88%) were negative. Seventy-nine samples were retested by a second-generation anti-HCV assay composed of recombinant capsid and NS proteins of HCV. Both assays had a nearly perfect agreement (Kappa value = 0.91). Of the positive cases, 31% were positive for reactivity to capsid only. Most (60/74, 81%) of the cases positive for synthetic peptide assay were HCV RNA positive, indicating potential infectivity. On the basis of the results of synthetic peptide assay, univariate analysis showed that history of paid sex for longer than 6 months, blood transfusion, acupuncture, intravenous drug abuse, and age over 20 years were significant risk factors of HCV infection (P < 0.01). Elevated alanine aminotransferase levels (> 40 U/L) were positively associated with anti-HCV, while the presence of serum hepatitis B surface antigen was a negatively associated factor. Multivariate analysis revealed that history of paid sex for longer than 6 months and blood transfusion were positively associated with anti-HCV (P < 0.001). The latter only accounted for less than one fifth of the HCV-infected prostitutes. This study indicates strongly that sexual transmission is an important route for HCV infection in prostitutes. This risk group may spread HCV to other populations as a sexually transmitted disease. PMID- 8492104 TI - Partial nucleotide sequencing and characterization of human parvovirus B19 genome DNAs from damaged human fetuses and from patients with leukemia. AB - While human parvovirus B19 is associated with fetal damage and chronic suppression of bone marrow in patients with leukemia, much less is known of the genomic characteristics of B19 isolated from damaged human fetuses and leukemia patients. B19 genome DNAs from human fetal organs and fluids and sera from leukemia patients were amplified by the polymerase chain reaction. The nucleotide sequences of amplified products in the region between nucleotide (nt) 3141 and nt3411 were determined following molecular cloning in M13 phage. The genome types of B19 from the fetuses and leukemia patients were similar to the types from patients with aplastic crisis and an asymptomatic individual. Wide diversity of the nucleotide sequence, i.e., six or more (6-11) substitutions, were evident in ten M13 phage clones of each DNA source from fetal materials, while substitutions in sera from patients with leukemia and aplastic crisis and of an asymptomatic individual numbered four or fewer (0-4). This wide diversity of B19 viruses in the fetus, revealed after many rounds of DNA replication, probably depends on a persistent state of infection. PMID- 8492105 TI - Evidence of persistent measles virus infection in Crohn's disease. AB - Transmission electron microscopy was used to examine the microvasculature of perfusion-fixed tissues from Crohn's disease and control patients. Paramyxovirus like particles, and inclusions consisting of condensations of nucleocapsid, in giant cells and endothelium at foci of vascular injury were identified in all 9 Crohn's disease patients. Tissues from patients with Crohn's disease were also examined by either in situ hybridisation (n = 10) or immunohistochemistry (n = 15), and compared to inflammatory and noninflammatory controls (n = 22). Hybridisation for measles virus N-protein genomic RNA was positive in all cases of Crohn's disease localising to foci of granulomatous vasculitis and lymphoid follicles. Positive immunohistochemical staining for measles virus nucleocapsid protein was positive in 13 of 15 patients with Crohn's disease, localising to foci of granulomatous inflammation. Hybridisation for measles virus RNA was positive in a minority of control intestinal tissues; viral inclusions were not seen ultrastructurally. Immunostaining was negative in control cases of intestinal tuberculosis. These observations suggest that measles virus is capable of causing persistent infection of the intestine and that Crohn's disease may be caused by a granulomatous vasculitis in response to this virus. PMID- 8492106 TI - A model of selective synapse formation in sympathetic ganglia. AB - In the sympathetic system, neurons from several spinal segments are mapped onto targets in the periphery in a topographically ordered way by means of selective synaptic connections in the superior cervical ganglion. Experimental evidence points to a crucial role for chemoaffinity in establishing this topographic map. Furthermore, rearrangements of synapses after surgical manipulations indicate that this chemoaffinity is not based on rigid "key-and-lock" markers. Our model is used to study how such nonrigid markers may interact with other regulatory factors, including growth-regulating signals and the growth potential of individual neurons. In the model, these latter factors are limiting, so that an increasing number of synaptic contacts decreases the likelihood of further synapse formation. These factors are combined with chemoaffinity using a linear threshold model. The model is robust to parameter changes and reproduces experimental observations with reasonable detail. Simulation results are used to discuss characteristic experimental results, such as the substantial plasticity of the connections seen after partial denervation. A surprisingly small effect of transient hyperinnervation in the model may help explain why final connectivities are similar in two real situations with high and low degrees of transient hyperinnervation (development and adult reinnervation). It is shown that spatial restrictions on post-synaptic neurons (dendrites) may contribute significantly to the segmentally broad innervation of each ganglion cell. Finally, we discuss potential effects of presynaptic neuronal death in systems with a high degree of plasticity. PMID- 8492107 TI - Brachially innervated ectopic hindlimbs in the chick embryo. I. Limb motility and motor system anatomy during the development of embryonic behavior. AB - The functional status of brachially innervated hindlimbs, produced by transplanting hindlimb buds of chick embryos in place of forelimb buds, was quantified by analyzing the number and temporal distribution of spontaneous limb movements. Brachially innervated hindlimbs exhibited normal motility until E10 but thereafter became significantly less active than normal limbs and the limb movements were more randomly distributed. Contrary to the findings with axolotls and frogs, functional interaction between brachial motoneurons and hindlimb muscles cannot be sustained in the chick embryo. Dysfunction is first detectable at E10 and progresses to near total immobility by E20 and is associated with joint ankylosis and muscular atrophy. Although brachially innervated hindlimbs were virtually immobile by the time of hatching (E21), they produced strong movements in response to electrical stimulation of their spinal nerves, suggesting a central rather than peripheral defect in the motor system. The extent of motoneuron death in the brachial spinal cord was not significantly altered by the substitution of the forelimb bud with the hindlimb bud, but the timing of motoneuron loss was appropriate for the lumbar rather than brachial spinal cord, indicating that the rate of motoneuron death was dictated by the limb. Measurements of nuclear area indicated that motoneuron size was normal during the motoneuron death period (E6-E10) but the nuclei of motoneurons innervating grafted hindlimbs subsequently became significantly larger than those of normal brachial motoneurons. Although the muscle mass of the grafted hindlimb at E18 was significantly less than that of the normal hindlimb (and similar to that of a normal forelimb), electronmicroscopic examination of the grafted hindlimbs and brachial spinal cords of E20 embryos revealed normal myofiber and neuromuscular junction ultrastructure and a small increase in the number of axosomatic synapses on cross-sections of motoneurons innervating grafted hindlimbs compared to motoneurons innervating normal forelimbs. The anatomical data indicate that, rather than being associated with degenerative changes, the motor system of the brachial hindlimb of late-stage embryos is intact, but inactive. PMID- 8492108 TI - Resealing of the proximal and distal cut ends of transected axons: electrophysiological and ultrastructural analysis. AB - The fates of the proximal and distal segments of transected axons differ. Whereas the proximal segment usually recovers from injury and regenerates, the distal segment degenerates. In the present report we studied the kinetics of the recovery processes of both proximal and distal axonal segments following axotomy and its temporal relations to the alterations in the cytoarchitecture of the injured neuron. The experiments were performed on primary cultured metacerebral neurons (MCn) isolated from Aplysia. We transected axons while monitoring the changes in transmembrane potential and input resistance (Rn) by inserting intracellular microelectrodes into the soma and axon. Correlation between the electrophysiological status of the injured axon and its ultrastructure was provided by rapid fixation of the neuron at selected times postaxotomy. Axotomy leads to membrane depolarization from a mean of -55.7 S.D. 12.8 mV to -12.7 S.D. 3.3 mV and decreased Rn from tens of M omega to 1-3 M omega. The transected axons remained depolarized for a period of 10-260 s for as long as the axoplasm was in direct contact with the bathing solution. Rapid repolarization and partial recovery of Rn was associated with the formation of a membrane seal over the cut ends by the constriction and subsequent fusion of the axolema. Prior to the formation of a membraneous barrier, electron-dense deposits aggregate at the tip of the cut axon and appear to form an axoplasmic "plug." Electrophysiological analysis revealed that this "plug" does not provide resistance for current flow and that the axoplasmic resistance is homogenously distributed. The kinetics of injury and recovery processes as well as the ultrastructural changes of the proximal and distal segments are identical suggesting that the different fates of the segments cannot be attributed to differences in the immediate response of the segments to axotomy. PMID- 8492109 TI - Dendritic development in the dorsal lateral geniculate nucleus of ferrets in the postnatal absence of retinal input: a Golgi study. AB - In order to determine the ongoing role of retinal fibers in the development of dorsal lateral geniculate nucleus (dLGN) neurons during postnatal development, the development of dLGN neurons in the postnatal absence of retinal input was studied in pigmented ferrets using the Golgi-Hortega technique. The development of four dLGN cell classes, defined on the basis of somatic and dendritic morphology, was described previously in normal ferrets (Sutton and Brunso Bechtold, 1991, J. Comp. Neurol. 309:71-85). The present results indicate that the morphological development of dLGN neurons is strikingly similar in normal and experimental ferrets. The exuberant dendritic appendages that appear after eye opening in normal ferrets are overproduced and eliminated in the postnatal absence of retinal input; however, the final reduction of these transient appendages is delayed. Because exuberant appendages develop in the absence of retinal input, their production cannot depend upon visual experience. Differences in cell body size between normal and experimental ferrets are apparent only after neurons can be classified at the end of the first postnatal month. Cell body size is markedly reduced for class 1 neurons; class 2 cells also are reduced in size but to a far lesser extent. As there is a general trend for class 1 neurons to have the functional properties of Y-cells, it is likely that the dLGN neurons most affected by the absence of retinal input also are Y-cells. PMID- 8492110 TI - Brachially innervated ectopic hindlimbs in the chick embryo. II. The role of supraspinal input in the loss of limb motility. AB - Brachially innervated grafted hindlimbs display a progressive loss of motility as development proceeds. However, the virtually immobile grafted hindlimbs of E20 embryos exhibited strong, synchronous contractions of gastrocnemius and tibialis muscles upon intraperitoneal injection of strychnine nitrate (20 micrograms). This result indicated that the marked behavioral deficit was not due to an inability of the motoneurons that innervate the immobile grafted hindlimbs to initiate and propagate action potentials, but was probably the result of an effective loss of motoneuron excitation. To examine the hypothesis that interaction with the supraspinal nervous system is involved in the reduction of grafted hindlimb activity, the normal forelimb and grafted hindlimb movements of chronic spinal embryos were examined. The normal forelimbs of chronic spinal embryos exhibited the same number of movements as normal embryos at all stages examined. Thus the deficit in grafted hindlimb motility is not comparable to the behavior of the normal forelimb in chronic spinal embryos and is, therefore, unlikely to be due to a lack of excitation from the supraspinal nervous system. The possibility of an inhibitory influence via supraspinal projections was examined in chronic spinal embryos that had brachially innervated grafted hindlimbs. After E12, the grafted hindlimbs of chronic spinal embryos displayed significantly fewer movements than the normal forelimbs of chronic spinal embryos but significantly more movements than the brachial hindlimb of embryos with intact spinal cords. By E18, however, both spinal and nonspinal brachial hindlimbs, were equally dysfunctional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492111 TI - Sensitivity of neurite outgrowth to microfilament disruption varies with adhesion molecule substrate. AB - Interactions between the cytoskeleton and cell adhesion molecules are presumed responsible for neurite extension. We have examined the role of microfilaments in neurite outgrowth on the cell adhesion molecules L1, P84, N-CAM, and on laminin. Cerebellar neurons growing on each substrate exhibited differing growth cone morphologies and rates of neurite extension. Growth of neurites in the presence of cytochalasin B (CB) was not inhibited on substrates of L1 or P84 but was markedly inhibited on N-CAM. Neurons on laminin were initially unable to extend neurites in the presence of CB but recovered this ability within 9 h. These studies suggest that neurite outgrowth mediated by different cell adhesion molecules proceeds via involvement of distinct cytoskeletal interactions. PMID- 8492112 TI - Acceleration of axonal outgrowth in rat sciatic nerve at one week after axotomy. AB - Following injury of sciatic motor axons in the rat, the rate of axonal outgrowth is faster if there has been a prior "conditioning" axotomy. The acceleration of outgrowth is due to an acceleration of SCb, the rate [slow (SC)] component of axonal transport that carries cytomatrix proteins; this occurs throughout the axon by 7 days after the conditioning axotomy (Jacob and McQuarrie, 1991a, J. Neurobiol. 22:570-583). To further characterize the conditioning lesion effect (CLE), it is important to know (1) the minimum effective conditioning interval (time between conditioning and testing lesions), (2) whether the cell body reaction is required, and (3) whether outgrowth accelerates after a single axotomy. Outgrowth distances were measured by radiolabeling all newly synthesized neuronal proteins and detecting those carried to growth cones by fast axonal transport. When the conditioning and testing lesions were made simultaneously (0 day conditioning interval), there was no CLE. With a conditioning interval of 3 days, there was a shortening of the initial delay (before the onset of outgrowth) without a change in outgrowth rate. With conditioning intervals of 7, 14, and 21 days, the rates of outgrowth were increased by 8%, 22%, and 11%, respectively. To determine whether the cell body reaction to axotomy is necessary for the CLE, a nonaxotomizing stimulus to axonal growth (partial denervation) was used in place of a conditioning axotomy. This had no effect on the rate of outgrowth from a testing lesion made 14 days later. Finally, we examined the possibility that outgrowth accelerates after a single lesion. Outgrowth was faster at 6-9 days after axotomy than at 3-6 days (p < 0.001), and accelerated further at 9-12 days (p < 0.001). We conclude that (1) the shortest effective conditioning interval is 3 days; (2) the cell body reaction is necessary for the CLE; (3) axonal outgrowth from a single axotomy accelerates in concert with the anabolic phase of the cell body reaction. The SCb motor is, in turn, upregulated by this reaction. This suggests that the SCb motor responds to a fast-transported signal that is a product of the cell body reaction. PMID- 8492113 TI - Selective fasciculation as a mechanism for the formation of specific chemical connections between Aplysia neurons in vitro. AB - Selective fasciculation of growth cones along preestablished axon pathways expressing matching or complementary adhesion molecules is thought to be an important strategy in axon guidance. Growth cone inhibiting factors also appear to influence pathfinding decisions. We have used identified Aplysia neurons in vitro to explore the hypothesis that similar mechanisms could be involved in target selection. Co-cultures of L10 neurons with RB neuron targets or R2 neurons with RUQ neuron targets reliably formed chemical connections. In contrast, co cultures of L10 with RUQ targets usually failed to form detectable chemical connections unless cell-cell contact was forced during plating by intertwining the major axons. These data suggested that differences in the ability to form cell-cell contacts might underlie the observed synaptic specificity. This notion was supported when fluorescent dye fills of L10 and R2 revealed a positive correlation between the amount of target contact and the frequency of synapse formation: L10-RUQ cultures showed much less target contact than L10-RB or R2-RUQ cultures. To examine the cellular mechanisms of these differences in target contact, presynaptic growth cones were observed as they interacted with target processes. L10-RUQ cultures showed much less fasciculation and more avoidance behavior compared to L10-RB and R2-RUQ cultures. This initial specificity suggested that the differences in amount of target contact arose through selective fasciculation and avoidance rather than through selective elimination after indiscriminate fasciculation. Selective fasciculation and avoidance might, therefore, aid in target selection by regulating the amount of contact between presynaptic processes and potential target cells. PMID- 8492114 TI - Hormone-induced changes in identified cell populations of the higher vocal center in male canaries. AB - Male canaries revise their vocal repertoire every year. Early work indicated that the volume and neuron number of the song-control nucleus HVC (Higher Vocal Center) declined in late-summer/fall as birds added and deleted syllables from their repertoire, and increased in spring as the set of song syllables stabilized to a fixed number. Seasonal variation in serum testosterone levels suggested that these changes in brain and behavior were regulated by testosterone (T). However, although initial studies describing growth and regression of HVC used Nissl staining to define its borders, recent experiments that have measured the distribution of identified populations of HVC cells (projection neurons, hormone target cells) suggest that there are no seasonal changes in HVC volume or neuron number. In order to clarify the role of T in the regulation of HVC morphology, we castrated male canaries, maintained them on short (fall-like) days, and treated them with either T, antisteroid drugs, or nothing. After 1 month of treatment, we used a double-labeling technique to characterize HVC projection neurons and androgen target cells. The results showed that hormonal manipulation influenced HVC volume, the density and size of HVC cells, and the absolute number and percentage of androgen target cells in HVC. Hormonal manipulation did not influence the absolute number of cells in HVC. Moreover, the distribution of projection neurons, androgen target cells, and the Nissl-defined borders of HVC were closely aligned in all experimental groups, indicating that exposure to T and/or its metabolites (estradiol and dihydrotestosterone) regulates the overall size of HVC by affecting the distributions of both projection neurons and androgen target cells. Analysis of double-labeling results suggests that T specifically influences both cell size and the ability to accumulate androgen among HVC neurons that project to the robust nucleus of the archistriatum (RA). The results of this study show that steroid hormones exert potent effects on HVC morphology in male canaries, but differences between our results and studies of seasonal males suggest there may be additional factors that can regulate HVC morphology. PMID- 8492115 TI - Brain phospholipids as dietary source of (n-3) polyunsaturated fatty acids for nervous tissue in the rat. AB - In a previous work, we calculated the dietary alpha-linolenic requirements (from vegetable oil triglycerides) for obtaining and maintaining a physiological level of (n-3) fatty acids in developing animal membranes as determined by the cervonic acid content [22:6(n-3), docosahexaenoic acid]. The aim of the present study was to measure the phospholipid requirement, as these compounds directly provide the very long polyunsaturated fatty acids found in membranes. Two weeks before mating, eight groups of female rats (previously fed peanut oil deficient in alpha linolenic acid) were fed different semisynthetic diets containing 6% African peanut oil supplemented with different quantities of phospholipids obtained from bovine brain lipid extract, so as to add (n-3) polyunsaturated fatty acids to the diet. An additional group was fed peanut oil with rapeseed oil, and served as control. Pups were fed the same diet as their respective mothers, and were killed at weaning. Forebrain, sciatic nerve, retina, nerve endings, myelin, and liver were analyzed. We conclude that during the combined maternal and perinatal period, the (n-3) fatty acid requirement for adequate deposition of (n-3) polyunsaturated fatty acids in the nervous tissue (and in liver) of pups is lower if animals are fed (n-3) very long chain polyunsaturated fatty acids found in brain phospholipids [this study, approximately 60 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 130 mg/1,000 kcal] rather than alpha-linolenic acid from vegetable oil triglycerides [200 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 440 mg/1,000 kcal]. PMID- 8492116 TI - Brain purines in a genetic mouse model of Lesch-Nyhan disease. AB - Mice carrying a mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) have recently been produced to provide an animal model for Lesch-Nyhan disease. The current studies were conducted to characterize the consequences of the mutation on the expression of HPRT and to characterize potential changes in brain purine content in these mutants. Our results indicate that the mutant animals have no detectable HPRT immunoreactive material on western blots and no detectable HPRT enzyme activity in brain tissue homogenates, confirming that they are completely HPRT deficient (HPRT-). Despite the absence of HPRT-mediated purine salvage, the animals have apparently normal brain purine content. However, de novo purine synthesis, as measured by [14C]formate incorporation into brain purines, is accelerated four- to fivefold in the mutant animals. This increase in the synthesis of purines may protect the HPRT- mice from potential depletion of brain purines despite complete impairment of HPRT-mediated purine salvage. PMID- 8492117 TI - Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. AB - The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4 triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione. PMID- 8492118 TI - Developmentally regulated secreted factors control expression of muscarinic receptor subtypes in embryonic chick retina. AB - Two molecular mass subtypes of muscarinic receptor are expressed by the chick retina (72 and 86 kDa). During development, the ratio of subtypes changes, with the 72-kDa form becoming predominant. We have found that subtypes switch can occur in retina cell culture, and have investigated factors that influence this in vitro increase in the 72-kDa receptor. Increases similar to those in vivo occurred when cells were cultured at 10(5) cells/cm2, but not at 10-fold lower density. High-density cultures, maintained on coverslips, showed no receptor development when transferred to large volumes of fresh medium, indicating that cell-cell contact alone was not responsible for induction. However, replacement of fresh medium with conditioned medium (from high-density cultures) resulted in normal induction. There were no morphological differences between cultures with high and low levels of the 72-kDa receptor. Conditioned medium also induced 72 kDa receptors in low-density cultures, consistent with a minimal role for cell cell contact. Efficacy of conditioned medium was markedly dependent on age. Media from cells cultured 1-4 days had no effect, but media from cells cultured 5-8 and 1-8 days elicited 1.6-fold and fourfold increases in the 72-kDa subtype, respectively. The data indicate that maturing retina cells secrete developmentally regulated factors that are necessary for abundant expression of the 72-kDa muscarinic receptor subtype. PMID- 8492119 TI - Presence of cyclic AMP response element-binding protein in oligodendrocytes. AB - Several lines of evidence indicate that cyclic AMP (cAMP) induces oligodendrocytes differentiation. However, the mechanism(s) of this stimulation remains unknown. Because in several cell types the transcriptional activity of various cAMP-responsive genes is regulated through a cis-acting DNA sequence known as cAMP response element (CRE), we investigated the possible presence of a CRE binding (CREB) protein in myelinating oligodendrocytes. A double-stranded oligonucleotide containing a tandem repeat of the CRE sequence was labeled with T4 kinase in the presence of [32P]ATP and then incubated with a nuclear protein extract from 14-day-old rat brain oligodendrocytes. The reaction mixture was then electrophoresed on nondenaturing polyacrylamide gels. The results indicated the presence of a protein that specifically binds to the CRE sequence. The results were supported by southwestern blotting assays in which the CRE probe bound to a approximately 45-kDa protein species. In separate experiments, it was shown that the 45-kDa protein can be phosphorylated in vitro by the catalytic subunit of protein kinase A. Developmental analysis of CREB protein expression indicated a peak at 14 days of age, preceding the peak of myelinogenesis. PMID- 8492120 TI - Rapid phosphorylation of phospholipase C gamma 1 by brain-derived neurotrophic factor and neurotrophin-3 in cultures of embryonic rat cortical neurons. AB - Phospholipase C gamma 1 (PLC-gamma 1) is involved at an early step in signal transduction of many hormones and growth factors and catalyzes the hydrolysis of phosphatidylinositol (PI) 4,5-bisphosphate to diacylglycerol and inositol trisphosphate, two potent intracellular second messenger molecules. The transformation of PC12 cells into neuron-like cells induced by nerve growth factor is preceded by a rapid stimulation of PLC-gamma 1 phosphorylation and PI hydrolysis. The present study analyzed the effects of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on phosphorylation of PLC-gamma 1 in primary cultures of embryonic rat brain cells. BDNF and NT-3 stimulated the phosphorylation of PLC-gamma 1, followed by hydrolysis of PI. The stimulation of PLC-gamma 1 phosphorylation occurred within 20 s after addition of BDNF or NT-3 and lasted up to 30 min, with a peak after 4 min. ED50 values were similar for BDNF and NT-3, with approximately 25 ng/ml. Phosphorylation of PLC-gamma 1 by BDNF and NT-3 was found in cultures from all major brain areas. K-252b, a compound known to inhibit selectively neutrophin actions by interfering with the phosphorylation of trk-type neutrophin receptors, prevented the BDNF- and NT-3 stimulated phosphorylation of PLC-gamma 1. Receptors of the trk type were coprecipitated with anti-PLC-gamma 1 antibodies. The presence of trkB mRNA in the cultures was substantiated by northern blot analysis. The action of BDNF and NT-3 seems to be neuron specific because no phosphorylation of PLC-gamma 1 was observed in cultures of nonneuronal brain cells. The results provide evidence that developing neurons of the cerebral cortex and other brain areas are responsive to BDNF and NT-3, and they indicate that the transduction mechanism of BDNF and NT-3 in the brain involves rapid phosphorylation of PLC-gamma 1 followed by PI hydrolysis. PMID- 8492121 TI - Increased acetylcholine content induced by adenosine in a sympathetic ganglion and its subsequent mobilization by electrical stimulation. AB - The present study was initiated to examine the effects of ATP on acetylcholine (ACh) synthesis. The exposure of superior cervical ganglia to ATP increased ACh stores by 25%, but this effect was also evident with ADP, AMP, and adenosine, but not with beta gamma-methylene ATP, a nonhdydrolyzable analogue of ATP, or with inosine, the deaminated product of adenosine. Thus, we attribute the enhanced ACh content caused by ATP to the presence of adenosine derived from its hydrolysis by 5'-nucleotidase. The adenosine-induced increase of tissue ACh was not the consequence of an adenosine-induced decrease of ACh release. The extra ACh remained in the tissue for more than 15 min after the removal of adenosine, but it was not apparent when ganglia were exposed to adenosine in a Ca(2+)-free medium. Incorporation of radiolabelled choline into [3H]ACh was also enhanced in the presence of adenosine, suggesting an extracellular source of precursor. Moreover, the synthesis of radiolabelled forms of phosphorylcholine and phospholipid was not reduced in adenosine's presence, suggesting that the extra ACh was not likely derived from choline destined for phospholipid synthesis. Aminophylline did not prevent the adenosine effect to increase ACh content; this effect was blocked by dipyridamole, but not by nitrobenzylthioinosine (NBTI). In addition, two benzodiazepine stereoisomers known to inhibit stereoselectively the NBTI-resistant nucleoside transporter displayed a similar stereoselective ability to block the effect of adenosine. Together, these results argue that adenosine is transported through an NBTI-resistant nucleoside transporter to exert an effect on ACh synthesis. The extra ACh accumulated as a result of adenosine's action was releasable during subsequent preganglionic nerve stimulation, but not in the presence of vesamicol, a vesicular ACh transporter inhibitor. We conclude that the mobilization of ACh is enhanced as a result of adenosine pretreatment. PMID- 8492122 TI - Acrylamide and glycidamide impair neurite outgrowth in differentiating N1E.115 neuroblastoma without disturbing rapid bidirectional transport of organelles observed by video microscopy. AB - The nature of the pathogenic insult in acrylamide neuropathy is unknown, but axonal transport disturbances are suspected. Using N1E.115 neuroblastoma in vitro, we examined acrylamide and related compounds in terms of general cytotoxicity, ability to block neurite outgrowth, and effects on neurite integrity and fast axonal transport. Acrylamide, glycidamide, and methylene-bis acrylamide were weakly cytotoxic in a 51Cr-release assay, but only at > or = 10 mM (order of efficacy: methylene-bis-acrylamide > glycidamide > acrylamide). Neurite outgrowth by differentiating cells was inhibited at 100-fold lower concentrations, with similar EC50 values for all three toxicants, i.e., acrylamide, 70 +/- 15 microM; methylene-bis-acrylamide, 92 +/- 31 microM; glycidamide, 120 +/- 30 microM. Only glycidamide (1 mM) caused degeneration of established neurites within a period of 48 h. Video-enhanced contrast differential interference contrast microscopy was used to test the effect of acrylamide and glycidamide on organelle transport in the neurites. In exposures of < or = 48 h at 1 mM, neither toxicant altered bidirectional organelle flux, measured as organelles transported per minute per micrometer of neurite diameter. Anterograde and retrograde organelle speeds were also undisturbed. These results suggest that mechanisms other than direct inhibition of organellar motility are responsible for acrylamide's neurotoxicity in vivo. PMID- 8492123 TI - Taurine-induced regeneration of goldfish retina in culture may involve a calcium mediated mechanism. AB - A possible mechanism of action of taurine as a trophic substance was studied in goldfish retina by investigating the effect of extracellular and intracellular calcium chelators on in vitro outgrowth, and the effect of taurine on calcium influx into postcrush retinal cells in culture. The amino acid stimulated the outgrowth from goldfish retinal explants, an effect that was blocked by EGTA and 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid methyl ester (BAPTA). The influx of calcium into cultured cells from postcrush retina was increased by taurine by day 5 in culture, but not by day 10, supporting previous results indicating a critical period in which taurine stimulates outgrowth. The present results suggest that taurine partially exerts its regenerative effect on postcrush retinal explants by increasing calcium influx. PMID- 8492124 TI - S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices. AB - The present study demonstrates that S(-)-nornicotine evoked a concentration dependent increase in dopamine (DA) release from superfused rat striatal slices. The increase in DA release was indicated by an S(-)-nornicotine-induced overflow of endogenous 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatal superfusate and by an S(-)-nornicotine-induced increase in tritium overflow from striatal slices preloaded with [3H]DA. Low concentrations (0.01-1.0 microM) of S(-) nornicotine, which did not evoke endogenous DOPAC overflow, also were unable to modulate electrically evoked DOPAC overflow. The increase in DOPAC overflow induced by S(-)-nornicotine was compared with that produced by S(-)-nicotine. Comparing equimolar concentrations (0.1-100 microM) of S(-)-nornicotine and S(-) nicotine, superfusion with S(-)-nornicotine resulted in a significantly greater DOPAC overflow. In contrast to the effect of S(-)-nicotine, S(-)-nornicotine evoked a sustained increase in DOPAC overflow for the entire period of S(-) nornicotine exposure. Furthermore, DOPAC overflow evoked by S(-)-nornicotine in control Krebs buffer was inhibited by superfusion with a low-calcium buffer. Moreover, in the low-calcium buffer, DOPAC overflow induced by 30 and 100 microM S(-)-nornicotine was not different from that with no S(-)-nicotine, tobacco products and a known metabolite of S(-)-nicotine, increases DA release in a calcium-dependent manner in superfused rat striatal slices. It is interesting that unlike S(-)-nicotine, there does not appear to be desensitization to this effect of S(-)-nornicotine. PMID- 8492125 TI - Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors. AB - Aromatic L-amino acid decarboxylase (AAAD) activity is enhanced in the striatum of control and MPTP-treated mice after administration of a single dose of the dopamine receptor antagonists haloperidol, sulpiride, and SCH 23390. MPTP-treated mice appear more sensitive to the antagonists, i.e., respond earlier and to lower doses of antagonists than control mice. The rise of AAAD activity induced by the antagonists is prevented by pretreatment with cycloheximide. The apparent Km values for L-3,4-dihydroxyphenylalanine (L-DOPA) and pyridoxal 5-phosphate appear unchanged after treatment with the antagonists. Increased AAAD activity was observed also after subchronic administration of dopamine receptor antagonists or treatment with reserpine. A single dose of a selective dopamine receptor agonists had no effect on AAAD activity. In contrast, administration of L-DOPA, quinpirole, or SKF 23390 for 7 days lowers AAAD activity in the striatum. We conclude that AAAD is modulated in striatum via dopaminergic receptors. PMID- 8492126 TI - Inorganic phosphate compartmentation in the normal isolated canine brain. AB - In vivo 31P magnetic resonance spectra of 16 isolated dog brains were studied by using a 9.4-T wide-bore superconducting magnet. The observed Pi peak had an irregular shape, which implied that it represented more than one single homogeneous pool of Pi. To evaluate our ability to discriminate between single and multiple peaks and determine peak areas, we designed studies of simulated 31Pi spectra with the signal-to-noise (S/N) ratios ranging from infinity to 4.4 with reference to the simulated Pi peak. For the analysis we used computer programs with a linear prediction algorithm (NMR-Fit) and a Marquardt-Levenberg nonlinear curve-fit algorithm (Peak-Fit). When the simulated data had very high S/N levels, both methods located the peak centers precisely; however, the Marquardt-Levenberg algorithm (M-L algorithm) was the more reliable at low S/N levels. The linear prediction method was poor at determining peak areas; at comparable S/N levels, the M-L algorithm determined all peak areas relatively accurately. Application of the M-L algorithm to the individual experimental in vivo dog brain data resolved the Pi peak into seven or more separate components. A composite spectrum obtained by averaging all spectral data from six of the brains with normal O2 utilization was fitted using the M-L algorithm. The results suggested that there were eight significant peaks with the following chemical shifts: 4.07, 4.29, 4.45, 4.62, 4.75, 4.84, 4.99, and 5.17 parts per million (ppm). Although linear prediction demonstrated the presence of only three peaks, all corresponded to values obtained using the M-L algorithm. The peak indicating a compartment at 5.17 ppm (pH 7.34) was assigned to venous pH on the basis of direct simultaneous electrode-based measurements. On the basis of earlier electrode studies of brain compartmental pH, the peaks at 4.99 ppm (pH 7.16) and 4.84 ppm (pH 7.04) were thought to represent interstitial fluid and the astrocyte cytoplasm, respectively. PMID- 8492127 TI - Synthesis of deoxyglucose-1-phosphate, deoxyglucose-1,6-bisphosphate, and other metabolites of 2-deoxy-D-[14C]glucose in rat brain in vivo: influence of time and tissue glucose level. AB - When the kinetics of interconversion of deoxy[14C]glucose ([14C]DG) and [14C]DG-6 phosphate ([14C]DG-6-P) in brain in vivo are estimated by direct chemical measurement of precursor and products in acid extracts of brain, the predicted rate of product formation exceeds the experimentally measured rate. This discrepancy is due, in part, to the fact that acid extraction regenerates [14C]DG from unidentified labeled metabolites in vitro. In the present study, we have attempted to identify the 14C-labeled compounds in ethanol extracts of brains of rats given [14C]DG. Six 14C-labeled metabolites, in addition to [14C]DG-6-P, were detected and separated. The major acid-labile derivatives, DG-1-phosphate (DG-1 P) and DG-1,6-bisphosphate (DG-1,6-P2), comprised approximately 5 and approximately 10-15%, respectively, of the total 14C in the brain 45 min after a pulse or square-wave infusion of [14C]DG, and their levels were influenced by tissue glucose concentration. Both of these acid-labile compounds could be synthesized from DG-6-P by phosphoglucomutase in vitro. DG-6-P, DG-1-P, DG-1,6 P2, and ethanol-insoluble compounds were rapidly labeled after a pulse of [14C]DG, whereas there was a 10-30-min lag before there was significant labeling of minor labeled derivatives. During the time when there was net loss of [14C]DG 6-P from the brain (i.e., between 60 and 180 min after the pulse), there was also further metabolism of [14C]DG-6-P into other ethanol-soluble and ethanol insoluble 14C-labeled compounds. These results demonstrate that DG is more extensively metabolized in rat brain than commonly recognized and that hydrolysis of [14C]DG-1-P can explain the overestimation of the [14C]DG content and underestimation of the metabolite pools of acid extracts of brain. Further metabolism of DG does not interfere with the autoradiographic DG method. PMID- 8492128 TI - [3H]adenosine transport in synaptoneurosomes of postmortem human brain. AB - [3H]Adenosine transport was characterized in cerebral cortical synaptoneurosomes prepared from postmortem human brain using an inhibitor-stop/centrifugation method. The adenosine transport inhibitors dipyridamole and dilazep completely and rapidly blocked transmembrane fluxes of [3H]adenosine. For 5-s incubations, two kinetically distinguishable processes were identified, i.e., a high-affinity adenosine transport system with Kt and Vmax values of 89 microM and 0.98 nmol/min/mg of protein, respectively, and a low-affinity adenosine transport system that did not appear to be saturable. For incubations with 1 microM [3H]adenosine as substrate, intrasynaptoneurosomal concentrations of [3H]adenosine were 0.26 microM at 5 s and 1 microM at 600 s. Metabolism of accumulated [3H]adenosine to adenine nucleotides was 15% for 5-s, 23% for 15-s, 34% for 30-s, 43% for 60-s, and 80% for 600-s incubations. The concentrations (microM) of total accumulated 3H-purines ([3H]adenosine plus metabolites) at these times were 0.3, 0.5, 1.0, 1.3 and 5.6, respectively. These results indicate that in the presence of extensive metabolism, the intrasynaptoneurosomal accumulation of 3H-purines was higher than the initial concentration of 1 microM [3H]adenosine in the reaction medium. For 5-, 15-, 30-, 60-, and 600-s incubations in the presence of the adenosine deaminase inhibitor EHNA and the adenosine kinase inhibitor 5'-iodotubercidin, metabolism of the transported [3H]adenosine was 14, 14, 16, 14, and 38%, respectively. During these times, total 3H-purine accumulation was 0.3, 0.5, 0.5, 0.7, and 1.8 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492129 TI - Regional variation in gamma-aminobutyric acid turnover: effect of castration on gamma-aminobutyric acid turnover in microdissected brain regions of the male rat. AB - This study compared the turnover of GABA neurons in different brain areas of the male rat and examined the effect of castration on GABA turnover in regions of the brain associated with the control of gonadotropin secretion. To estimate GABA turnover, GABA was quantified by HPLC in microdissected brain regions 0, 30, 60, 90, and 120 min after inhibition of GABA degradation by aminooxyacetic acid (100 mg/kg, i.p.). GABA accumulation was linear in all areas for 90 min (p < 0.01), and GABA turnover was estimated as the slope of the line formed by increased GABA concentration versus time, determined by linear regression. There was considerable regional variation both in the initial steady-state concentrations of GABA and in the rates of GABA turnover. Of 10 discrete brain structures, GABA turnover was highest in the medial preoptic nucleus and lowest in the caudate nucleus. Turnover times in the terminal fields of known GABAergic projection neurons ranged sevenfold, from 2.6 h in the substantia nigra to 0.4 h in the lateral vestibular nucleus. The effect of castration on GABA turnover in 13 microdissected brain regions was investigated by measuring regional GABA concentrations before and 30 min after injection of aminooxyacetic acid in intact rats or 2 or 6 days postcastration. Following castration, steady-state GABA concentrations were increased, and GABA turnover decreased in the diagonal band of Broca, the medial preoptic area, and the median eminence. GABA turnover increased in the medial septal nucleus and was unaffected in the cortex, striatum, and hindbrain. These results are consistent with the hypothesis that testosterone negative-feedback control of luteinizing hormone-releasing hormone involves steroid-sensitive GABAergic neurons in the rostral and medial basal hypothalamus. PMID- 8492130 TI - Phosphorylation of neuronal kinesin heavy and light chains in vivo. AB - The microtubule-based motor protein kinesin is thought to drive anterograde organelle transport in axons, but nothing is known about how its force-generating activity or organelle-binding properties are regulated. Studies in other motility systems suggest that protein phosphorylation is a reasonable candidate for this function. I report here that the kinesin heavy chain (HC) and light chain (LC), as well as the 160-kDa kinesin-associated protein kinectin, are phosphorylated in vivo in cultures of chick sympathetic neurons and PC12 cells labeled metabolically with 32P. In neurons, both kinesin chains are phosphorylated exclusively on serine residues, and limiting tryptic digestion demonstrated that the phosphorylation sites are clustered in a region of < or = 5 kDa for the HC and < or = 14 kDa for the LC. Partial tryptic digestion of 32P-labeled HC followed by immunoblotting with SUK4 monoclonal anti-HC and fluorography showed that the sites of HC phosphorylation are outside the globular N-terminal head region where kinesin's microtubule-binding and mechanochemical activities reside. Treatment of metabolically labeled neurons with forskolin, phorbol esters, or calcium ionophore did not alter the extent of phosphorylation, the phosphoamino acid composition, or the V8 protease phosphopeptide maps of the HC, LC, and 160 kDa protein, with one exception: treatment with calcium ionophore reduced the specific activity of the LC. In addition, when kinesin from PC12 cells was compared with that from PC12-derived cell lines lacking protein kinase A activity, neither the extent of phosphorylation nor the phosphopeptide maps were altered for either chain. Phosphopeptide mapping experiments also showed that postlysis kinase activity can phosphorylate both the neuronal HC and LC at sites not phosphorylated in vivo. PMID- 8492131 TI - Regional heterogeneity of polyamine effects on the N-methyl-D-aspartate receptor in rat brain. AB - Polyamines have pronounced effects on N-methyl-D-aspartate (NMDA) receptors in vitro and may be important modulators of NMDA receptor activity in vivo. There is considerable regional heterogeneity in the effects of polyamines on [3H]MK-801 binding in rat brain sections. For example, spermidine enhances the binding of [3H]MK-801 to a much greater extent in the striatum than in the cortex. To further explore the basis for this regional heterogeneity, the effects of polyamines on [3H]MK-801 binding were measured in well-washed membranes prepared from frontal cortex and striatum. There was no difference in the concentration response relationship for spermidine or the KD for [3H]MK-801 in the presence of 75 microM spermidine, suggesting that the regional difference seen in tissue sections is due to an endogenous factor that is either removed or inactivated during the preparation of membranes. Comparison of spermidine concentration response curves in washed and unwashed tissue sections revealed that washing selectively enhanced the Emax value in the ventromedial caudate putamen without changing the EC50. This is consistent with the possibility that a noncompetitive polyamine antagonist is being removed from this region during washing. There was no regional variability in the effects of the putative inverse agonist 1,10 diaminodecane, consistent with recent suggestions that this polyamine inhibits the NMDA receptor at a site distinct from the one at which polyamines act to enhance NMDA receptor function. Agents that modulate the redox state of the NMDA receptor did not eliminate the regional heterogeneity of polyamine effects. Furthermore, the stimulatory effect of glycine in these regions did not correlate with that of spermidine. These results suggest the existence of one or more endogenous factors that noncompetitively influence the effects of polyamines in a region-specific manner. PMID- 8492132 TI - Effects of chronic morphine treatment on beta-endorphin-related peptides in the caudal medulla and spinal cord. AB - The effects of chronic morphine treatment on beta-endorphin (beta E) immunoreactive (beta E-ir) peptide levels were determined in the rat caudal medulla and different areas of the spinal cord. Seven days of morphine pelleting had no effect on total beta E-ir peptides in the caudal medulla. In contrast, it significantly increased beta E-ir peptide concentrations in the cervical and thoracic regions of the spinal cord compared with placebo-pelleted controls, whereas in the lumbosacral region this trend did not reach statistical significance. Injections of the opiate receptor antagonist naloxone 1 h before the rats were killed had no effect on the morphine-induced increases in the cord. Chromatographic analyses revealed that enzymatic processing of beta E-related peptides in the spinal cord seemed unaffected by the morphine and/or naloxone treatments. In light of previous data showing that morphine down-regulates beta E biosynthesis in the hypothalamus, the present results suggest that the regulation of beta E-ir peptides in the spinal cord is distinct from that found in other CNS areas. These data provide support for previous results suggesting that beta E expressing neurons may be intrinsic to the spinal cord. PMID- 8492133 TI - (+)-Anatoxin-a is a potent agonist at neuronal nicotinic acetylcholine receptors. AB - The effects of the nicotinic agonist (+)-anatoxin-a have been examined in four different preparations, representing at least two classes of neuronal nicotinic receptors. (+)-Anatoxin-a was most potent (EC50 = 48 nM) in stimulating 86Rb+ influx into M10 cells, which express the nicotinic receptor subtype comprising alpha 4 and beta 2 subunits. A presynaptic nicotinic receptor mediating acetylcholine release from hippocampal synaptosomes was similarly sensitive to (+)-anatoxin-a (EC50 = 140 nM). alpha-Bungarotoxin-sensitive neuronal nicotinic receptors, studied using patch-clamp recording techniques, required slightly higher concentrations of this alkaloid for activation: Nicotinic currents in hippocampal neurons were activated by (+)-anatoxin-a with an EC50 of 3.9 microM, whereas alpha 7 homooligomers reconstituted in Xenopus oocytes yielded an EC50 value of 0.58 microM for (+)-anatoxin-a. In these diverse preparations, (+) anatoxin-a was between three and 50 times more potent than (-)-nicotine and approximately 20 times more potent than acetylcholine, making it the most efficacious nicotinic agonist thus far described. PMID- 8492134 TI - Secretogranin II is synthesized and secreted in astrocyte cultures. AB - Astrocyte cultures from rat brain were analyzed for their ability to synthesize and secrete secretogranin II (chromogranin C). Northern blot analysis of polyA selected RNA established the presence of secretogranin II mRNA in these cells. By radioimmunoassay, 11.6 fmol/10(6) astrocytes of secretogranin II was found in these cells. About twice the amount was released into the medium within 3 days. Secretogranin II within the astrocytes was practically unprocessed, as shown by HPLC. These results establish for the first time that astrocytes in vitro synthesize and secrete a protein of the acidic chromogranin family. PMID- 8492135 TI - In vivo imaging of vesicular monoamine transporters in human brain using [11C]tetrabenazine and positron emission tomography. AB - The pharmacokinetics of [11C]tetrabenazine, a high-affinity radioligand for the monoamine vesicular transporter, were determined in living human brain using in vivo imaging by positron emission tomography (PET). The radiotracer showed high brain uptake and rapid washout from all brain regions with relatively slower clearance from regions of highest concentrations of monoamine vesicular transporters (striatum), resulting in clear differential visualization of these structures at short intervals after injection (10-20 min). As the first human PET imaging study of a vesicular neurotransmitter transporter, these experiments demonstrate that external imaging of vesicular transporters forms a new and valuable approach to the in vivo quantification of monoaminergic neurons, with potential application to the in vivo study of neurodegenerative disorders such as Parkinson's disease. PMID- 8492136 TI - Adenosine A2a receptor modulation of electrically evoked endogenous GABA release from slices of rat globus pallidus. AB - Adenosine A2a receptors have been localized to GABAergic striatopallidal neurons, but their functional role is unknown. To address this question, the modulation of endogenous GABA release by adenosine A2a receptors was examined in slices of rat globus pallidus. The selective adenosine A2a receptor agonist CGS-21680 (3.0-10 nM) significantly increased electrically stimulated release (overflow) of GABA, with 10 nM CGS-21680 resulting in a 44% increase compared with the control. Both the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 microM) and the selective A2a receptor antagonist KF-17837 (100 nM) abolished the CGS 21680-induced increase in GABA overflow. Higher concentrations of CGS-21680 (0.10 1.0 microM) decreased GABA overflow by approximately 25%. 8-Phenyltheophylline (10 microM) antagonized these effects, whereas KF-17837 (100 nM) did not, suggesting actions of CGS-21680 on other adenosine receptors at these concentrations. These results demonstrate that activation of adenosine A2a receptors augments electrically stimulated release of GABA from globus pallidus slices and suggest a mechanism by which adenosine may modulate GABAergic output from the striatopallidal efferent system. PMID- 8492137 TI - Distribution of 125I-ferrotransferrin binding sites in the mesencephalon of control subjects and patients with Parkinson's disease. AB - Iron is abnormally accumulated in the substantia nigra pars compacta of patients with Parkinson's disease (PD). Because neuronal and glial iron uptake seems to be mediated by the binding of ferrotransferrin to a specific high-affinity receptor on the cell surface, the number of transferrin receptors could be altered in this disease. The regional distribution of specific binding sites for human 125I diferric transferrin has been studied in the mesencephalon, on cryostat-cut sections from autopsy brains of control subjects and parkinsonian patients by in vitro autoradiography. Densities of binding sites were highest in the central gray substance (approximately 10 fmol/mg of tissue equivalent), intermediate in the catecholaminergic cell group A8, superior colliculus, and ventral tegmental area, and almost nonexistent in the substantia nigra. The density of 125I transferrin binding sites was not significantly different between parkinsonian and control brains in any region analyzed. These results show that in the mesencephalon the regional density of transferrin binding sites is lowest in the dopaminergic cell groups, which are the most vulnerable to PD, and suggest that iron does not accumulate through an increased density of transferrin receptors at the level of the substantia nigra. PMID- 8492138 TI - Neuronal and glial gene expression in neocortex of Down's syndrome and Alzheimer's disease. AB - The association cortex of Down's syndrome (DS) predictably and prematurely undergoes neurofibrillary degeneration of Alzheimer type. Hence studies of DS are potentially useful in defining the earliest pathogenetic events in Alzheimer's disease (AD). Previous reports have described altered expression of several mRNAs in AD cortex; but the pathogenetic stage at which expression of these mRNAs begins to deviate from the norm has not been defined. We have examined this issue in neocortex of DS. Expression of mRNAs, known to be altered in AD cortex, was studied by Northern analysis, comparing frontal cortex of DS (15-45 years) with age-matched controls and with AD. Chromosome 21- and non-21-encoded mRNAs were studied, including transcripts expressed preferentially in neurons (neurofilament light subunit and amyloid precursor transcripts) and in glia (glial fibrillary acidic protein [GFAP] and S100 beta). Chromosome 21-encoded mRNAs were increased in DS cortex as expected. Except in the DS case with extensive neurofibrillary degeneration, GFAP was expressed at levels significantly below the control, suggesting that trisomy 21 exerts a suppressive effect on GFAP gene expression. We found no instance in which AD-type changes of transcript expression preceded the appearance of neurofibrillary degeneration. The findings indicate that in trisomy 21, certain changes of mRNA prevalence previously described for AD neocortex are not a necessary antecedent to neurofibrillary degeneration. PMID- 8492139 TI - Relative importance of basement membrane and soluble growth factors in delayed and immediate regeneration of rat sciatic nerve. AB - Sciatic nerve regeneration was studied in two groups of rats. In group I, nerves were transected and transplanted immediately to the contralateral side. In group II, nerves were transected and transplanted 30 days later to the contralateral side. At 4 weeks, group II had an average nerve action potential amplitude of 784 +/- 292 microV and 43.2% +/- 6.7% of myelinated fibers were > 4 microns in diameter. In comparison, the respective measurements were 94 +/- 35.6 microV (p = 0.05) and 29.5% +/- 1.9% (p = 0.04) in group I. At 8 weeks, there were no significant differences in these measurements between groups. These data suggest that the environment in the distal stump improves early regeneration of nerve fibers when that stump was transected 30 days earlier. These and previous findings suggest that soluble trophic factors may be important in initiation of axonal regeneration. PMID- 8492140 TI - Pathology of experimental compression neuropathy producing hyperesthesia. AB - An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light and electron microscopy at different time points from 1 day to 12 weeks after surgery. Edema was the initial pathologic change seen in the neuropathy and was associated with early Wallerian degeneration on day 1. Injury to the connective tissue sheaths with interruption of the perineurial layer, infiltration of macrophages into the endoneurium, and proliferation of endothelial cells were observed during the first week. Endothelial cells hypertrophied and changed to a rhomboid shape with gaps between adjacent cells. Most large myelinated and many small myelinated fibers underwent Wallerian degeneration. Unmyelinated fiber numbers were reduced to one-third of the normal value from day 5 to day 14. Axonal sprouts were numerous after 1 week and grew into the segment distal to the ligatures by 4 weeks. Aberrant sprouts in minifascicles outside the perineurium were present from 4 weeks on. The original ligatures were rapidly surrounded by large amounts of fibrous tissue and mostly absorbed by 12 weeks; the initial fascicular compression caused by the ligatures was maintained by the fibrous tissue. We conclude that, whereas neuroma formation may contribute to the pain-related behavior in the later stages of this neuropathy, acute changes in the endoneurial microenvironment are important for its initial development. PMID- 8492141 TI - Relative neural toxicity of local anesthetics. AB - In rat sciatic nerve, relative neural toxicity and relative motor nerve conduction blockade were assessed for two amide-linked local anesthetics (etidocaine and lidocaine) and two ester-linked local anesthetics (chloroprocaine and procaine). As measures of neural toxicity, nerve fiber injury and edema were assayed by light microscopic examination of nerve tissue sampled 2 days after perineural (next to the sciatic nerve) injection of various concentrations of the local anesthetics. Both nerve injury and edema increased with concentration of local anesthetics, but injury was frequently present in nerve fascicles with little or no edema. In parallel studies, the amplitude of the electrical activity elicited from the interosseous muscles of the foot following ipsilateral electrical stimulation at the sciatic notch was monitored for up to 15 minutes to assess the extent of motor nerve blockade. The resulting log concentration response curves were analyzed for differences in potency. Both for injury and for conduction block, the order of decreasing potency was: etidocaine, lidocaine, chloroprocaine, procaine. These results are not consistent with the proposal that ester-linked agents are more likely than other local anesthetic agents to cause nerve injury. PMID- 8492142 TI - In vitro expression of neural tube pathology in the vl mutant mouse. AB - The pathogenesis of lumbosacral spinal dysraphism was analyzed in vitro in early homozygous embryos of the vl (vacuolated lens) mutant mouse, and comparisons were made between the lag in closure of the posterior neuropore at the beginning of culture and the degree of severity in the spinal defect at the end of culture for each embryo. In the majority of abnormal (vl/vl) embryos, the neural tube closed completely in culture, although mild defects were observed in the spinal roofplate comparable to those that occur in vivo. Although some abnormal embryos did exhibit small openings in the caudal neural tube at the end of the culture period, in none of the cultured embryos was the extent and severity of the defect as great as that observed in some abnormal embryos of comparable age obtained in vivo. Moreover, the degree of delay in closure of the posterior neuropore at the outset of culture did not necessarily correlate with the severity of the defect obtained at the end of culture. Thus, the expression of the neural tube defect in this mutant appears to be modulated and attenuated by biochemical and/or mechanical factors which may be peculiar to the culture milieu. PMID- 8492143 TI - Computer simulations of motoneuron firing rate modulation. AB - 1. As a human subject slowly increases the amount of force exerted by a muscle, the discharge rates of low-threshold motor units saturate at a rather low level, whereas higher-threshold units continue to be recruited and undergo increases in their discharge rates. The presently known intrinsic properties of motor units do not produce this "rate limiting." 2. Using computer simulations of a model motoneuron pool, we tested the hypothesis that rate limiting can be accounted for on the basis of the known distributions of synaptic input from different sources. The properties of the simulated motor units and their synaptic inputs were based as closely as possible on the available experimental data. A variety of simulated synaptic input organizations were applied to the pool, and the resulting outputs were compared with the data on rate limiting in human subjects. 3. We found that the data on rate limiting in human subjects greatly constrained the possible organizations of characterized synaptic input systems. Only when the synaptic organization included a gradual "crossover" between two specific types of input systems could the human data be accurately reproduced. Low input/output levels relied on a system organized like the monosynaptic Ia input, which produces greater effective synaptic currents in low- than in high-threshold motor units. Above a sharply defined crossover level, all further increases in output were produced by a system organized like the oligosynaptic rubrospinal input, which generates the opposite pattern. PMID- 8492144 TI - PET study of voluntary saccadic eye movements in humans: basal ganglia thalamocortical system and cingulate cortex involvement. AB - 1. The purpose of this work was to explore the cortical and subcortical mechanisms underlying the execution of voluntary saccadic eye movements in humans. 2. Normalized regional cerebral blood flow (NrCBF) was measured using positron emission tomography (PET) and H2(15O) bolus intravenous injections in four right-handed healthy volunteers at rest and while performing self-paced voluntary horizontal saccadic eye movements in total darkness. 3. Magnetic resonance imaging of each subject's brain was matched to PET images, allowing the detection of activation in individually defined anatomic regions of interest. Cortical regions were drawn according to gyri limits; subcortical structures were also defined. 4. Self-paced saccadic eye movements elicited bilateral NrCBF increases in the lenticular nuclei, including putamen and globus pallidus, and in the thalamus. At the cortical level, we found bilateral NrCBF increases in the precentral gyrus, the superior part of the median frontal gyrus that corresponds to the supplementary motor area. There was also a significant NrCBF increase in the cerebellar vermis. 5. Right fusiform and lingual gyri, right insula, and left cingulate gyrus were also activated during the execution of saccades. 6. These results indicate that the classical basal ganglia-thalamocortical motor loop previously described for skeletal movements may also be involved in simple saccadic eye movements in humans. PMID- 8492145 TI - Sound direction influences the frequency-tuning characteristics of neurons in the frog inferior colliculus. AB - 1. We investigated the influence of sound direction on the frequency-tuning characteristics of neurons in the frog inferior colliculus, the torus semicircularis. For each neuron, we used tone bursts to determine the frequency threshold curves (FTCs) for three to seven loudspeaker azimuths. The loudspeaker was mounted on a rotatable arc and could be swung through the frontal field between positions opposite the ear that was contralateral to the recording site (C90 degrees) and the ear that was ipsilateral to the recording site (I90 degrees). 2. Frequency-tuning data from 83 units showed that the characteristic frequency (CF) shift through a 180 degrees change in loudspeaker azimuth was typically small, i.e., 85% of neurons showed maximum absolute changes in CF that were < 0.4 octaves. Paired comparisons of CFs for each neuron when the loudspeaker was located at C90 degrees, and the frontal midline position (0 degree) revealed no significant differences (P > 0.2) between azimuths. The magnitude of CF shift between different sound directions showed no systematic pattern. 3. In contrast to the CF, midbrain neurons showed distinct changes in the minimum threshold (MT) at CF across 180 degrees of azimuth. The maximum absolute change in MT ranged from 0 to 38 dB, with a mean of 10.9 dB. A pair-wise comparison of MTs, for each neuron, derived with the speakers at C90 degrees, 0 degree, and I90 degrees, revealed that the MT typically increased when the loudspeaker was rotated toward I90 degrees (P < 0.0001). 4. The most prominent effect of rotating the loudspeaker from C90 degrees to I90 degrees was a narrowing of the FTC. Sharpness of tuning in simple V-shaped FTCs was most directly shown by changes in the Q factors at 10, 20, and 30 dB above MT as a function of sound direction. A pair-wise comparison for individual neurons showed that all Q factors were significantly larger (sharper tuning) for I90 degrees compared with C90 degrees (P < 0.02). The Q20dB values were also significantly larger for I90 degrees compared with 0 degree (P < 0.05). For the majority of units, the maximum Q10dB and Q20 dB values were displayed when the loudspeaker was positioned at I90 degrees; however, the maximum Q30dB was distributed nearly equally for the three azimuths. These results suggest that a change in sound direction has the most robust effect on tuning properties of the FTCs nearest the MT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492146 TI - Visually induced cross-axis postsaccadic eye drift. AB - 1. It has been previously shown that, if a visual pattern is transiently moved just after every saccade, it is possible to induce horizontal, postsaccadic, ocular drift after horizontal saccades that persists in the dark. In this study we show that horizontal ocular drift can also be created after vertical saccades. Five human subjects viewed binocularly the interior of a full-field hemisphere filled with a random-dot pattern. They were encouraged to make frequent vertical saccades. During training, eye movements were recorded by the electrooculogram. A computer detected the end of every saccade and immediately moved the pattern to the left after up saccades and right after down saccades. The motion was exponential, its amplitude was 25% of the vertical component of the antecedent saccade, its time constant was 50 ms. Before and after 2-3 h of training, movements of both eyes were measured by the eye-coil/magnetic-field method while subjects were instructed to make vertical saccades in the dark, in the presence of the movable adapting pattern, and between stationary targets for calibration. 2. After training (approximately 20,000 saccades) all subjects developed a zero latency, exponential ocular drift to the left after up saccades and to the right after down saccades. The amplitude of the horizontal drift, expressed as a percentage of the vertical component of the preceding saccade, was 2.7% in the dark. This rose to 10.2% in the presence of the movable adapting stimulus. The latter rise is not due to visual following systems but to a zero-latency increase in initial drift velocity. 3. The horizontal drifts were usually unequal between the two eyes, indicating the presence of disconjugate movements. We measured intrasaccadic disconjugate horizontal movements of all subjects. In agreement with studies by others of saccades in the light, we measured a divergence during up saccades (1.3 degrees) and a convergence for down (0.4 degrees), but in this case for spontaneous saccades in the dark. After training, these values increased for saccades in the dark but decreased in the light in the presence of the adapting stimulus. These changes were largely idiosyncratic and statistically significant in only a few subjects. 4. The cross-axis postsaccadic drifts were separated into their conjugate and disconjugate components. The disconjugate components were small and idiosyncratic, and the means were small for saccades in the dark. The only consistent trend was in the presence of the adapting stimulus where up saccades were often followed by convergence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492147 TI - Serotonin-operated potassium current in CA1 neurons dissociated from rat hippocampus. AB - 1. The intracellular mechanisms of serotonin (5-HT) response were investigated in dissociated rat hippocampal pyramidal neurons using the nystatin-perforated patch technique. 2. Under voltage-clamp conditions, 5-HT evoked outward currents (I5 HT) with an increase in membrane conductance at a holding potential of -40 mV. The outward current reversed at the K+ equilibrium potential, which shifted 59.4 mV with a 10-fold change in extracellular K+ concentration. 3. The first application of 5-HT on neurons perfused with Ca(2+)-free external solution induced outward currents of I5-HT but the amplitude was diminished dramatically with successive applications. Pretreatment with the membrane-permeant Ca2+ chelator 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA-AM) also diminished the I5-HT amplitude. 4. Pretreatment with pertussis toxin (PTX) had no effect on I5-HT. 5. The I5-HT was not cross-desensitized with the caffeine-induced outward current but with outward current mediated by the muscarinic acetylcholine receptor. Pretreatment with Li+ significantly enhanced the I5-HT, indicating that I5-HT is involved in the elevation of intracellular free Ca2+ released from inositol triphosphate (IP3) sensitive Ca2+ store sites but not from the caffeine-sensitive ones. 6. The calmodulin (CaM) antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide (W-7), inhibited I5-HT in a concentration-dependent manner. 7. The Ca2+/CaM-dependent protein kinase II inhibitor 1-[N,O-Bis (5 isoquinolinesulfonyl)-N-methyl-L-tyrosil]-4-phenylpiperazine depressed the I5 HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492148 TI - Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats. AB - 1. In barbiturate-anesthetized cats we examined the interaction of lactic acid and static contraction on the discharge of group III muscle afferents. Only afferents whose receptive fields were located in the triceps surae muscles were studied. 2. Twelve of 20 afferents were stimulated by a 60-s static contraction. The majority of firing occurred within the first few seconds of contraction. Thirteen of 20 afferents were stimulated by femoral arterial injections of 24 mM lactic acid (1-4 ml) with the muscle at rest. Repeated injections of lactic acid with the muscle at rest led to tachyphylaxis. Lactic acid was then injected (24 mM; 4 ml) during the last 15 s of static contraction. In eight of nine afferents that were tachyphylactic to lactic acid with the muscle at rest, we noted a restored sensitivity to lactic acid during contraction. 3. In separate experiments we examined the effects of dichloroacetate (DCA) on the responses of group III muscle afferents to static contraction. DCA reduces the production of lactic acid by increasing levels of the active form of the enzyme pyruvate dehydrogenase. 4. DCA lowered arterial and venous lactate concentrations at rest and during contraction. DCA significantly decreased (31%; P < 0.05) the responses of the afferents to contraction. This effect was most prominent within the first 10 s of contraction and was not due to a reduced level of mechanical stimulation after DCA, because peak tension levels were the same during the two bouts of contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492149 TI - Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey. AB - 1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli. PMID- 8492150 TI - Barbiturate depresses simple spike activity of cerebellar Purkinje cells after climbing fiber input. AB - 1. Some scientists reported that the simple spike (SS) activity was transiently depressed after climbing fiber input, but others reported that predominant population of Purkinje cells increased their SS activity after the complex spike (CS). In the present study, SS activity after spontaneous CS was compared before and after the administration of pentobarbital sodium and of ketamine in high decerebrate cats. 2. Frequencies of spontaneous CS and SS firing were reduced (P < 0.001, t test) after pentobarbital administration of a total dose of 20-30 mg/kg. 3. In the peri-CS time histogram, the SS activity during a post-CS period of 10-110 ms with respect to that during a pre-CS period of -100-0 ms was reduced (P < 0.001) after the pentobarbital administration from, on average, 132.4 to 81.9%. In contrast, the SS activity during a post-CS period of 110-210 ms remained unchanged (P > 0.2). 4. In the pre-CS time histogram constructed after the pentobarbital administration, there were no significant differences (P > 0.01) between the SS activity during a pre-CS period of -600 to -500 ms and that during each of other pre-CS periods, suggesting that the barbiturate had little effect on the SS activity preceding the CS. 5. Analysis of raster diagrams revealed the variability of individual SS activity after the CS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492151 TI - Spatiotemporal organization of simple-cell receptive fields in the cat's striate cortex. I. General characteristics and postnatal development. AB - 1. Most studies of cortical neurons have focused on the spatial structure of receptive fields. For a more complete functional description of these neurons, it is necessary to consider receptive-field structure in the joint domain of space and time. We have studied the spatiotemporal receptive-field structure of 233 simple cells recorded from the striate cortex of adult cats and kittens at 4 and 8 wk postnatal. The dual goal of this study is to provide a detailed quantitative description of spatiotemporal receptive-field structure and to compare the developmental time courses of spatial and temporal response properties. 2. Spatiotemporal receptive-field profiles have been measured with the use of a reverse correlation method, in which we compute the cross-correlation between a neuron's response and a random sequence of small, briefly presented bright and dark stimuli. The receptive-field profiles of some simple cells are space-time separable, meaning that spatial and temporal response characteristics can be dissociated. Other cells have receptive-field profiles that are space-time inseparable. In these cases, a particular spatial location cannot be designated, unambiguously, as belonging to either an on or off subregion. However, separate on and off subregions may be clearly distinguished in the joint space-time domain. These subregions are generally tilted along an oblique axis. 3. Our observations show that spatial and temporal aspects of receptive-field structure mature with clearly different time courses. By 4 wk postnatal, the spatial symmetry and periodicity of simple-cell receptive fields have reached maturity. The spatial extent (or size) of these receptive fields is adult-like by 8 wk postnatal. In contrast, the response latency and time duration of spatiotemporal receptive fields do not mature until well beyond 8 wk postnatal. 4. By applying Fourier analysis to spatiotemporal receptive-field profiles, we have examined the postnatal development of spatial and temporal selectivity in the frequency domain. By 8 wk postnatal, spatial frequency tuning has clearly reached maturity. On the contrary, temporal frequency selectivity remains markedly immature at 8 wk. We have also examined the joint distribution of optimal spatial and temporal frequencies. From 4 wk postnatal until 8 wk postnatal, the range of optimal spatial frequencies increases substantially, whereas the range of optimal temporal frequencies remains largely unchanged. From 8 wk postnatal until adulthood, there is a large increase in optimal temporal frequencies for cells tuned to low spatial frequencies. For cells tuned to high spatial frequencies, the distribution of optimal temporal frequencies does not change much beyond 8 wk postnatal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492152 TI - Spatiotemporal organization of simple-cell receptive fields in the cat's striate cortex. II. Linearity of temporal and spatial summation. AB - 1. We have tested the hypothesis that simple cells in the cat's visual cortex perform a linear spatiotemporal filtering of the visual image. To conduct this study we note that a visual neuron behaves linearly if the responses to small, brief flashes of light are mathematically related, via the Fourier transform, to the responses elicited by sinusoidal grating stimuli. 2. We have evaluated the linearity of temporal and spatial summation for 118 simple cells recorded from the striate cortex (area 17) of adult cats and kittens at ages 4 and 8 wk postnatal. These neurons represent a subset of the population of cells for which we have described the postnatal development of spatiotemporal receptive-field structure in the preceding paper. Spatiotemporal receptive-field profiles are constructed, with the use of a reverse correlation technique, from the responses to random sequences of small bar stimuli that are brighter or darker than the background. Fourier analysis of spatiotemporal receptive-field profiles yields linear predictions of the cells' spatial and temporal frequency tuning. These predicted responses are compared with spatial and temporal frequency tuning curves measured by the use of drifting, sinusoidal-luminance grating stimuli. 3. For most simple cells, there is good agreement between spatial and temporal frequency tuning curves predicted from the receptive-field profile and those measured by the use of sinusoidal gratings. These results suggest that both spatial and temporal summation within simple cells are approximately linear. There is a tendency for predicted tuning curves to be slightly broader than measured tuning curves, a finding that is consistent with the effects of a threshold nonlinearity at the output of these neurons. In some cases, however, predicted tuning curves deviate from measured responses only at low spatial and temporal frequencies. This cannot be explained by a simple threshold nonlinearity. 4. If linearity is assumed, it should be possible to predict the direction selectivity of simple cells from the structure of their spatiotemporal receptive-field profiles. For virtually all cells, linear predictions correctly determine the preferred direction of motion of a visual stimulus. However, the strength of the directional bias is typically underestimated by a factor of about two on the basis of linear predictions. Consideration of the expansive exponential nonlinearity revealed in the contrast-response function permits a reconciliation of the discrepancy between measured and predicted direction selectivity indexes. 5. Overall, these findings show that spatiotemporal receptive-field profiles obtained with the use of reverse correlation may be used to predict a variety of response properties for simple cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492153 TI - Comparison of cerebellar and motor cortex activity during reaching: directional tuning and response variability. AB - 1. The responses of 262 motor cortex cells and 223 cerebellar neurons were recorded during whole-arm reaching movements toward targets lights in eight evenly distributed directions radiating from a common central starting position. The reaching movements were followed by a 2-s target hold period where a fixed arm posture was actively maintained to stabilize the hand over the target light. 2. Cerebellar neurons had a higher mean tonic discharge rate while holding over the starting position (22.9 imp/s) than did motor cortex cells (12.5 imp/s). The mean population response curve describing the changes in activities with movement direction was likewise shifted toward higher frequencies in the cerebellum compared with the motor cortex, but the amplitude of the two curves was about equal. Therefore, the baseline discharges of cerebellar neurons were higher, but their changes in activity during movement were similar to those of motor cortical cells. 3. Motor cortex neurons were more strongly related to active maintenance of different arm postures than were cerebellar units. This was shown by a larger posture-related population response curve in the motor cortex (half-wave amplitude of cosine function was 11.2 imp/s, compared with 7.0 imp/s for cerebellar neurons), which represented the average response curve calculated from all the cells of the population. Furthermore, the motor cortex population had a higher percentage of single cells with tonic responses while the hand was held over different targets (tonic and phasic-tonic cells composed 57% of motor cortex population, compared with 38% of cerebellar population). Proportionately more cerebellar cells were phasically related to the movements. 4. The majority of motor cortex cells (58%) showed reciprocal changes relative to the center-hold time activity where the activity increased for movements in the preferred direction and decreased for movements in the opposite direction. Most of the remaining cells (40%) showed graded changes where the activity increased gradually as reaching was directed closer to the preferred direction. In contrast, the most common cerebellar response pattern was graded (38%). Only 26% were reciprocal and 18% were non-directional. The remaining 2% of motor cortical cells and 18% of cerebellar neurons could not be readily assigned to any of these three response classes. 5. Sector widths were calculated to measure the dispersion of individual cerebellar and motor cortical cell activities about the eight movement directions. Sector widths calculated from the absolute activities were always broader for cerebellar neurons (i.e., the cells were more broadly tuned).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492154 TI - Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro. AB - 1. The mechanisms underlying the induction of long-term potentiation (LTP) in the medial and lateral perforant paths were studied by recording excitatory postsynaptic potentials (EPSPs) from rat dentate granule cells in vitro using extracellular and whole-cell recording techniques. 2. Paired stimuli (interstimulus interval, 50-1,000 ms) resulted in facilitation of the lateral and depression of the medial perforant path-evoked EPSPs, respectively. This physiological difference was used to isolate responses evoked by stimulation of a single path. 3. Tetanic stimulation induced LTP in both pathways, although the magnitude of LTP in the lateral perforant path was significantly less than that in the medial perforant path. Both forms of LTP were blocked by the N-methyl-D aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 4. Buffering intracellular calcium by loading granule cells with the calcium chelator bis (O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented LTP in both pathways. 5. Pairing of low-frequency (0.25 Hz) afferent stimulation with postsynaptic depolarization induced LTP in the medial but not the lateral perforant path. However, pairing of higher-frequency stimulation (1-4 Hz) with postsynaptic depolarization did potentiate the lateral perforant path-evoked EPSP in some cells. 6. Both the medial and lateral perforant path-evoked EPSPs had two components; a fast component blocked by the non-NMDA receptor antagonist 6-cyano 7-nitroquinoxaline-2,3-dione and a slower, voltage-dependent component blocked by D-APV. 7. The results indicate that the induction of LTP in both the medial and lateral perforant paths requires activation of postsynaptic NMDA receptors and a rise in intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492155 TI - Physiological properties of motoneurons innervating different muscle unit types in rat gastrocnemius. AB - 1. The contractile properties of gastrocnemius muscle units and the electrophysiological properties of their innervating motoneurons were examined in anesthetized adult male Sprague-Dawley rats in situ, using conventional microelectrode techniques. 2. Muscle units (n = 70) were classified as fast (F) or slow (S) on the basis of the degree of force summation during stimulation at 25 Hz, as well as fatigue resistance, in response to current injection into innervating motoneurons. S units categorized using these criteria were also found to invariably demonstrate twitch half-relaxation times (RT1/2) > 28 ms, with F units demonstrating RT1/2 < 27 ms. Some overlap was present between F and S units in twitch time-to-peck tension (TPT). 3. S muscle units were innervated by motoneurons with significantly higher afterhyperpolarization (AHP) times-to-peak and half-decay times, AHP amplitudes, and input resistances than F units. Motoneurons innervating S units also demonstrated slower mean axon conduction velocity than F units. 4. F units were further classified as fast fatiguing (FF), fast fatigue-resistant (FR), or fast intermediate (FI) on the basis of their fatigue resistance. Muscle unit forces were different among the unit types such that FF > FI > FR > S. Twitch TPT and RT1/2 differed such that FF < FI, FR < S. 5. No differences among FF, FI, and FR units were found for measures of AHP time course, AHP amplitude, rheobase, or input resistance. The only motoneuron property that differed among F unit types was axon conduction velocity, which was lower for FF than for FI and FR units. 6. The best relationships between muscle unit and motoneuron physiological properties were between expression of twitch time course, which included RT1/2 and AHP half-decay time (r = 0.73 to 0.74). S units always had AHP half-decay times > 20 ms, whereas for F units, values never exceeded 19 ms. Correlations between these variables increased when only S units were considered (r = 0.86-0.97), and were weak and not significant among F units only. 7. The only other significant correlations between muscle unit and motoneuron properties > 0.5 were between input resistance and expressions of twitch time course (r = 0.56-0.66). These relationships were nonexistent when type S units were not included in the analysis. 8. A sample of tibial motoneurons (n = 98) that innervated hindlimb muscles other than gastrocnemius was combined with the gastrocnemius motoneurons to examine interrelationships among motoneuron properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492156 TI - Prenatal development of the receptive fields of individual trigeminal ganglion cells in the rat. AB - 1. Extracellular single-unit recording and receptive-field mapping techniques were used to evaluate the response characteristics of trigeminal (V) ganglion cells in unanesthetized, decerebrate, fetal rats between the ages of embryonic (E ) day 15 and E-20 (E-0 is the day of conception). 2. The receptive-field properties of the cells (n = 282) recorded at all of these ages except E-15 were remarkably similar; V primary afferents were generally silent in the absence of peripheral stimulation (94.3%) and gave rapidly adapting responses to innocuous tactile stimuli (97.5%). Rapid response decrements to repeated stimuli were observed in 9 of the 14 cells (64%) tested. 3. None of the cells recorded were activated by either heat or cold. No attempt was made to evaluate responses to noxious mechanical stimuli. 4. Particular attention was paid to neurons whose receptive fields involved mystacial vibrissae follicles. At all ages, neurons were recorded that responded to indentation of the skin at the base of the vibrissae, but vibrissa deflection was not an adequate stimulus for any of the cells tested. At all ages, nearly all (89.0%) of the 127 cells with vibrissa related receptive fields responded to indentation of one and only one follicle. 5. These results indicate that the response properties (e.g., adaptation characteristics, ability to respond to repeated stimuli) of V primary afferents in fetal rats differ substantially from those of V ganglion cells in adult animals, but that the receptive-field size for these neurons in prenatal rats is, with very rare exceptions, adult-like from the earliest age at which they can be recorded. 6. These results, when considered together with the results of previous retrograde tracing experiments in fetal animals, suggest that the initial projections of V primary afferents to their peripheral targets may be quite accurate. PMID- 8492157 TI - Functional properties of spinal interneurons activated by muscular free nerve endings and their potential contributions to the clasp-knife reflex. AB - 1. The goal of this study was to characterize the functional properties of spinal interneurons that are excited by muscular free nerve endings and to assess their contributions to the clasp-knife reflex. 2. The patterns of activity of 82 spinal interneurons that were excited by squeezing the Achilles tendon or manipulation of the muscle surfaces, preferential stimuli for muscular free nerve endings, were extracellularly recorded in lamina V-VII of the L5-S1 spinal cord in decerebrated and spinalized cats. 3. Interneurons were uniformly excited by increases in muscular length and force. Responses to muscle stretch exhibited gradual decay during maintained stretch, afterdischarge after stretch release, and adaptation to repeated stretch. Responses to isometric contraction induced by electrical stimulation of motor axons was also prolonged after contraction, but did not decay during maintained contraction. For similar increases in force, stretch evoked greater excitation than contraction, indicating that both stretch and contraction contributed to interneuronal activity. Overall, the time course and magnitude of the interneuronal responses to stretch and contraction paralleled the time course and magnitude of the clasp-knife reflex. 4. Interneurons were powerfully excited by muscular free nerve endings, which mediate the clasp-knife reflex, and by cutaneous receptors. Only occasionally were they excited by primary spindle or Golgi tendon organ afferents, which suggests that activation of muscular free nerve endings mediated the interneuronal responses to stretch and contraction. 5. Simultaneous recordings of interneuronal activity and the clasp-knife reflex revealed a broad correlation between interneuronal activity and clasp-knife inhibition. 6. Because the patterns of activity of free nerve ending-responsive interneurons during stretch and contraction were similar to the clasp-knife reflex, were closely correlated with clasp-knife inhibition during simultaneous interneuronal and reflex recordings, and were powerfully excited by muscular free nerve endings, it is likely that the interneurons described above contributed to the clasp-knife reflex. 7. In contrast, a small number (n = 16) of interneurons were recorded that were only weakly excited by muscular free nerve endings but strongly excited by group I afferents, exhibited less spontaneous and evoked activity, and had significantly different responses to stretch and contraction. These interneurons are less likely to have contributed to the clasp-knife reflex. PMID- 8492158 TI - Bilateral inhibition by glycinergic afferents in the medial superior olive. AB - 1. Coincidence-detection of excitatory synaptic potentials has long been considered to be the mechanism by which medial superior olivary (MSO) neurons compute interaural time differences. Here we demonstrate the contribution of synaptic inhibition in this circuit using a gerbil brain slice preparation. 2. Nearly all cells exhibited excitatory postsynaptic potentials (EPSPs) and action potentials (APs) after stimulation of either the ipsilateral or contralateral afferent pathway. In 44% of cells, the latency of APs depended on stimulus amplitude, exhibiting shifts of 0.25-2 ms. 3. Nearly all neurons (89%) exhibited stimulus-evoked synaptic inhibition. The inhibitory effects were enhanced at greater stimulus amplitudes and were usually able to block synaptically evoked APs. In addition, APs and EPSPs were reversibly blocked by delivering the inhibitory transmitter glycine in almost all tested cells (91%). 4. In the presence of the glycine antagonist strychnine, the effects of synaptic inhibition were suppressed. 5. The stimulus level-dependent inhibitory potentials influenced the probability that an MSO neuron would fire an AP, as well as the precise timing. Therefore, the present results have implications for the processing of interaural time differences by the MSO and at higher auditory centers. PMID- 8492159 TI - Coincidence detection by binaural neurons in the chick brain stem. AB - 1. Neurons in nucleus laminaris (NL) of birds are the first to receive binaural information and are presumed to play a role in encoding interaural time differences (ITDs). We studied extracellular single-unit responses of NL neurons in slices of the auditory brain stem of the chick. The afferents to NL were activated by electrical stimulation of nucleus magnocellularis (NM) or the auditory nerve. Changes in responses were measured as the delay between trains of bilateral stimuli (the simulated interaural time difference or S-ITD, n = 26) was varied and as the interstimulus interval and stimulus amplitude were varied (n = 61). 2. The probability of an action potential and the action-potential latency varied as a function of interstimulus interval. Most NL neurons showed a greater response probability and a shorter response latency to an interstimulus interval between 2.5 and 3.5 ms. The interstimulus interval that produced the minimum response latency was slightly longer than the interval that produced the maximum response probability. In contrast, NM neurons (n = 4) showed no preferred rate, instead, the probability of firing increased as the interstimulus interval increased. 3. Responses to bilateral stimulation showed that NL neurons can act as coincidence detectors. NL neurons responded most reliably when activated simultaneously by their two inputs and, at favorable S-ITDs, two subthreshold inputs combined to produce an action potential. 4. NL neurons also exhibited inhibition during bilateral stimulation. At unfavorable S-ITDs a subthreshold input combined with a suprathreshold input produced fewer action potentials than evoked by the suprathreshold input alone. 5. The latency of the bilateral response varied as a function of S-ITD. At S-ITDs near coincidence the latency of the bilateral response was shorter than the latency of either of the unilateral responses. Away from coincidence, the latency of the bilateral response was largely determined by the latency of the stronger unilateral response. When the unilateral responses were of similar strength, the earlier stimulus determined the latency of the bilateral response. 6. The range of S-ITDs producing a maximal response varied as a function of stimulus strength but was never less than approximately 300 microseconds. This is greater than the maximum possible ITD of sound calculated for the chick's head size. From these data we hypothesize that, in the chick, single units cannot uniquely encode ITDs, but rather ITDs may be coded by the proportion of maximally firing cells along an isofrequency band in NL. PMID- 8492160 TI - Human flexor reflex modulation during cycling. AB - 1. Human flexor reflex (HFR) responses were elicited during ergometer cycling in neurologically intact humans with the objective of understanding the influence of lower limb muscle activity on phase-dependent reflex modulation during movement. The experimental setup permitted control over background muscle activity and stimulus intensity without significantly interfering with the cycling motion. 2. All experiments involved cycling on an ergometer at a set rate and workload. A 333-Hz, 15-ms pulse train of electrical stimulation was randomly delivered to the skin over the tibial nerve at the ankle at selected lower limb positions. In the first group of experiments, subjects were stimulated at six cycling phases while pedaling with normal, phasic ankle activity (free-form cycling). The second and third group of experiments involved stimulation under static limb positioning conditions and during active pedaling while subjects were asked to maintain a consistent background level of isolated tibialis anterior (TA) or soleus (SOL) electromyographic (EMG) activity. 3. Control criteria were established to assure similar isolated muscle EMG levels and sensory stimulation intensities throughout the experiments. With the aid of the application of a lower extremity brace and visual EMG feedback, SOL and TA activity were confined by the subject to a narrow range during the task of cycling. Stimulus consistency was achieved through maintenance of flexor hallucis brevis M-waves to within an envelope encompassing the mean value +/- 5% of the maximum M-wave amplitude in all experimental conditions. 4. When the subject's limb was statically positioned, the HFR responses in the SOL muscle showed no significant changes in pattern when compared at various limb positions. During cycling with consistent SOL activity, a response waveform pattern of early-latency-long-duration depression was followed by a later-latency facilitation response in all positions except the initial power phase. The initial power phase was characterized by an additional early-latency facilitation in all but one subject. 5. In the TA muscle response, no change in onset latency (57.5 +/- 0.8 ms, mean +/- SD), waveform pattern, or response amplitude (7.9 +/- 1.1% maximal voluntary contraction, mean +/- SD) was observed during static limb positioning. Significant increases in response amplitude (P < 0.05) coupled with significant increases (9.2 ms, P < 0.05) in onset latency were seen during the transition from the recovery phase to the power phase during cycling. In addition, there was no correlation between the prestimulation baseline level and the onset latency during controlled TA cycling activity conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492161 TI - Responses of inferior colliculus neurons to time-varying interaural phase disparity: effects of shifting the locus of virtual motion. AB - 1. Motion of sound sources results in temporal variation of the binaural cues for sound localization. We evaluated the influence of virtual motion on neural tuning to one of these cues, interaural phase disparity (IPD). Responses to dichotic stimuli were recorded from single units in the inferior colliculus of the anesthetized cat and gerbil (Meriones unguiculatus). Static IPDs were generated by presenting dichotic tone pairs with a constant phase offset maintained for the duration of the stimulus. Time-varying IPDs were generated by simultaneously presenting a pure tone to one ear and a phase-modulated tone to the other ear. Sets of time-varying stimuli consisted of modulations through partially overlapping ranges of IPD, corresponding to movement of a sound source through partially overlapping arcs in the horizontal plane. 2. In agreement with previous results, neuronal discharge was typically a peaked function of static IPD resulting from both binaural facilitation at favorable IPDs and binaural suppression at unfavorable IPDs. Responses to time-varying IPD stimuli appeared to be shaped by the same facilitative and inhibitory mechanisms that underlie static IPD tuning. Modulation toward the peak of binaural facilitation increased the probability of discharge, and modulation toward the peak of binaural suppression decreased the probability of discharge. However, it was also clear that IPD tuning could be significantly altered by the temporal context of the stimulus. For the vast majority of units in response to modulation through partially overlapping ranges of IPD the discharge rate profiles were generally nonoverlapping. This shift in IPD tuning induced by the virtual motion reflects the fact that the binaural interaction associated with a given IPD depends on the recent history of stimulation. In addition, modulation in opposite directions through the same range of IPDs often elicited asymmetric responses. These nonlinearities imply that most inferior colliculus neurons do not unambiguously encode a specific IPD, but instead may encode small changes of IPD occurring virtually anywhere within their receptive fields. In a few cases modulation through overlapping ranges of IPD elicited contiguous response profiles, indicating that for these units responses were determined entirely by instantaneous IPD. 3. The nonlinearity of responses to time-varying IPD stimuli could not be attributed to monaural entrainment to the phase-modulated signals, did not depend on the phase modulation waveform, and occurred irrespective of which ear received the phase-modulated signal. Responses were similar in cats and gerbils, suggesting that the underlying mechanisms are common to binaural processing in diverse mammalian species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492162 TI - Voltage-dependent sodium and calcium currents of rat myenteric neurons in cell culture. AB - 1. Inward currents of myenteric neurons that had been grown in cell cultures prepared from the small intestines of neonatal or young adult rats were studied with tight seal whole-cell recordings. The kinetic and pharmacological properties of these neurons were analyzed. 2. All neurons had rapidly inactivating, tetrodotoxin (TTX)-sensitive Na+ currents that could be evoked by steps to potentials more positive than -50 mV. Holding potentials more negative than -65 mV were necessary to remove steady-state inactivation. No TTX-insensitive Na+ currents were observed, thus the ability of subsets of myenteric neurons to fire action potentials in TTX must depend upon their density of Ca2+ channels. 3. Ca2+ and Ba2+ currents were studied in neurons perfused internally with CsCl to block K+ currents and bathed with solutions containing TTX and antagonists of K+ channels. Currents were significantly larger when Ba2+ replaced Ca2+ as the charge carrier. Cd2+ and Gd3+ blocked Ca2+ and Ba2+ currents rapidly and reversibly. High-voltage-activated (HVA) Ca2+ and Ba2+ currents were observed in all neurons. Too few neurons possessed detectable low-voltage-activated Ca2+ currents to permit detailed study. 4. HVA Ca2+ and Ba2+ currents evoked from holding potentials more negative than -50 mV could be divided into two kinetically distinguishable components with very different rates of inactivation. A "decaying" component inactivated relatively rapidly with a t1/2 of 25-75 ms. A "sustained" component inactivated quite slowly with a t1/2 of 1-5 s. At more positive holding potentials, only the sustained component was observed. Although the two kinetically distinguishable components had different current-voltage relationships, they had indistinguishable rates of deactivation: a single time constant was sufficient to fit the decay of tail currents. The relative amplitudes of the two components varied considerably among different neurons. 5. Ca2+ and Ba2+ currents could be divided into two pharmacologically distinct components on the basis of sensitivity to omega-conotoxin GVIA (I omega CgTX) and to dihydropyridine antagonists (IDHP). At holding potentials more positive than 70 mV, a combination of omega CgTX and DHPs completely blocked Ca2+ and Ba2+ currents in most neurons. At holding potentials more negative than -50 mV, I omega CgTX and IDHP each contained decaying and sustained components. I omega CgTX activated more slowly than did IDHP. The DHP agonist Bay K8644 increased the amplitude of IDHP and slowed its rate of deactivation. 6. The results suggest that myenteric neurons may have as few as two subtypes of HVA Ca2+ channels; omega CgTX-sensitive ones and DHP-sensitive ones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492163 TI - Epileptogenesis in chronically injured cortex: in vitro studies. AB - 1. Field potentials and intracellular activities were examined in neocortical slices obtained through areas of chronic cortical injury produced by cortical undercutting and transcortical lesions made in vivo 7-122 days before the terminal in vitro slice experiment. 2. Abnormal field potentials characterized by long- and variable-latency multiphasic events could be evoked by layer VI-white matter or subpial stimulation in 9 of 15 animals that had adequate partial cortical isolations. These "epileptiform" field potentials were recorded in layers II-V and propagated across the cortex. They appeared at threshold in an all-or-none fashion and, in most slices, could be blocked by increasing stimulus intensity. In one slice, spontaneous epileptiform events occurred that were similar to those evoked by extracellular stimulation. 3. Intracellular activities during the epileptiform field potentials consisted of polyphasic synaptic events that were predominantly depolarizing and that could last < or = 400-500 ms, synchronous with the field potential activities. A variety of observations suggested that the neuronal activities underlying epileptiform field potentials were relatively asynchronous and much less intense than those previously found in chemically induced epileptogenesis within the neocortex. 4. Inhibitory postsynaptic potentials (IPSPs) were not prominent in neurons when threshold stimuli evoked epileptiform events; however, suprathreshold stimuli could elicit biphasic IPSPs and block the long-latency polysynaptic activity and abnormal field potential in most slices. Depolarizing components of the polysynaptic activity had the appearance of excitatory postsynaptic potentials in terms of their responses to alterations in membrane potential. 5. Comparison of spike parameters in layer V neurons of epileptogenic slices with those in control layer V neurons showed no significant differences in spike height, threshold, duration, or rise time. Resting membrane potentials were also not significantly different. 6. There was a highly significant difference in input resistance (RN) between layer V neurons in control and injured slices; the mean value for neurons in lesioned cortex was 68.1 M omega, whereas that in control cells was 30.5 M omega. There was also a significant prolongation of the slow membrane time constant in neurons of injured cortex (19.4 ms) as opposed to that in control cells (12.2 ms), suggesting that a change in specific resistivity or capacitance contributed to the higher RNS. 7. The relationship between adapted spike frequency and applied current (f-I slope) was steeper in layer V neurons from injured cortical slices (44.3 Hz/nA) than in normal layer V cells (28.2 Hz/nA).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492164 TI - Spontaneous burst firing in cat primary auditory cortex: age and depth dependence and its effect on neural interaction measures. AB - 1. Neural activity was recorded with two independent electrodes separated by 0.5 2 mm, aligned in parallel, and advanced perpendicular to the surface of the cat auditory cortex. Because the experiments were part of a study into laminar interaction the difference in recording depths for the two independently movable electrodes was never > 100 microns. Multi-unit activity on each electrode was separated on-line into single-unit spike-trains with a maximum variance spike sorting algorithm. Off-line controls on the quality of the spike-train separation were routinely performed. The first aim of this study was to describe the age dependence of spontaneous burst firing and to explore if and how it could be explained by age dependent changes in firing rate. The second aim was to investigate a potential layer dependence on burst firing. The third aim was to describe the effect of burst-removal procedures on the shape, strength, and width of the cross-correlogram and to investigate whether an age dependence in burst firing might account for the previously reported age dependence in correlation strengths. 2. Recordings were made from 237 single units from primary auditory cortex in nine adult cats and from 67 units in seven kittens age 10-52 days. The incidence of burst firing as a function of firing rate, age and depth of recording and unit characteristic frequency was investigated. In addition the effect of burst firing on the strength and width of the central peak in 471 neural pair correlograms was analyzed. 3. Burst firing could be distinguished at many different time scales; bursts lasting of the order of 10 s contained bursts with durations of the order of 1 s, which in turn contained bursts of 30-50-ms duration. The analysis in this paper was restricted to the short-duration bursts. 4. Burst firing on the short-time scale of 50 ms was characterized by relatively well defined intervals between the first two spikes (3-15 ms) followed by higher order intervals with large spread (range 4-50 ms) but with increasing modal interval value. The typical adult five-spike burst template featured spikes at 0, 3.3, 14.6, 27.2, and 34.8 ms. Burst with fewer spikes showed larger intervals between the first three spikes. 5. The probability of occurrence of isolated spikes, pairs, triplets, etc. showed a power-law dependence on firing rate with a coefficient that was significantly lower than expected under Poisson firing conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492165 TI - Visual-response properties of units in the turtle cerebellar granular layer in vitro. AB - 1. Single units were recorded extracellularly in the turtle's cerebellar cortex from an isolated brain preparation during visual stimulation. Only a small fraction of the isolated units responded to visual stimuli. For these visually responsive units, the most effective visual stimulus was a moving check pattern that covered the entire surface of the retinal eyecup. The visually responsive units had little or no spontaneous spike activity, nor were they driven by flashes of diffuse light or stationary patterns. 2. All the visually responsive units were direction sensitive and were driven exclusively by the contralateral eye. This direction tuning was well fit by a limacon model (mean correlation coefficient, 0.89). The distribution of the entire sample indicates a slight preponderance of upward preferred directions. 3. The direction tuning of these cerebellar units was independent of stimulus contrast or the pattern's configuration (such as checkerboards or random check or dot patterns). In the preferred direction, a unit's spike frequency increased monotonically as a function of stimulus velocity until approximately 10 degrees/s, but remained direction sensitive (relative to the opposite direction) at speeds as fast as 100 degrees/s. 4. In some experiments the ventrocaudal brain stem was transected in the frontal plane just caudal to the cerebellar peduncles. Although this lesion presumably removes climbing fiber input from the inferior olivary nuclei, the visual-response properties in the cerebellar cortex were unaffected. 5. The response properties of these units indicate that they encode retinal slip information in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492166 TI - Electrophysiological evidence for a bisynaptic retinocerebellar pathway. AB - 1. Electrical microstimulation was applied to an in vitro turtle brain preparation while recording extracellular activity from the cerebellar cortex. A visual input to the cerebellum was investigated by measuring spike responses evoked by stimulation of drifting visual patterns imaged onto the contralateral retinal eyecup. A vestibular input was assessed by extracellular field potentials following brief current pulses through monopolar suction electrodes holding the eighth cranial nerve (nVIII). 2. The cortical topography of visual and vestibular inputs was first examined. Visual units and vestibular fields show considerable topographic overlap in the rostrolateral quadrant of the cerebellum. In addition, granule layer units were isolated that responded to current stimulation of nVIII (60-150 microA monopolar). In some cases, spikes occurred at short and fixed latency after each current pulse for stimulus frequencies of 100 Hz. The responses of these units suggest a direct path between the stimulating and recording electrodes without intervening synapses. Alternatively, extracellular units were also encountered that responded with longer, more variable latencies but only for low stimulation frequencies (< or = 20 Hz). Of the units that responded to nVIII stimulation, three units also responded to visual stimuli, yet those units all failed to follow high-frequency stimulation of nVIII. This cortical area may then be a site for convergence of visual and vestibular signals on postsynaptic cells. 3. The cellular identity of the visual units in the granule layer and the visual pathways leading there were next investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492167 TI - Timing of odor stimulation does not alter patterning of olfactory bulb unit activity in freely breathing rats. AB - 1. The effect of the timing between nasal airflow and ongoing tracheal respiration on single-unit activity in the olfactory bulb (OB) of the rat was examined. Nasal and tracheal breathing were dissociated with the use of a double tracheal cannulation technique that allowed independent control of nasal airflow and control of the synchronization of nasal airflow and tracheal breathing. 2. When amyl acetate-saturated air was presented to the nose, OB units showed a distinct reorganization of activity known as respiratory patterning. Of 43 cells examined, 29 fired maximally after inspiration, and 14 fired maximally after expiration. In all 43 cells the patterning of OB activity was synchronized with the time course of the nasal stimulation. This synchronization was independent of the point in the ongoing respiratory cycle (tracheal breathing) at which the odor stimulation was applied. 3. Patterning of OB single-unit activity was also observed when odor was applied as a series of "inspirations" without intervening expirations. Patterning was observed to follow the time course of the odor stimulation even when this was considerably longer and slower than normal breathing. No patterning of activity was observed during continuous odor stimulation or in the absence of odor stimulation. 4. It is concluded that respiratory patterning of OB single-unit activity in the rat is not directly dependent on centrifugal inputs synchronized to respiration. Rather, the observed pattern of neural activity reflects the phasic stimulation of the olfactory receptors with each inspiration and the dynamics of the circuitry intrinsic to the bulb itself. PMID- 8492168 TI - Intracellular recordings from morphologically identified neurons of the basolateral amygdala. AB - 1. Intracellular current-clamp recordings were made from neurons of the basolateral nucleus of the amygdala (BLA) of the rat in the in vitro slice preparation. Neurons were identified morphologically after intracellular injection of biocytin, and the electrophysiological properties and morphological characteristics were correlated. 2. Three distinct morphological subtypes were identified: Class I pyramidal neurons, Class I stellate neurons, and Class II neurons. Each morphological subtype could also be distinguished according to its characteristic electrophysiological properties. 3. Class I pyramidal neurons typically had pyramidal perikarya (cross-sectional area = 245 microns2) with spine-laden apical and basal dendrites. The axon originated from the largest basal dendrite and produced several collaterals that ramified throughout the dendritic arborization of the parent cell. These neurons were characterized electrophysiologically by their higher input resistance (65.6 M omega), long time constant of membrane charging tau 0 (27.8 ms), long duration action potential (half-width = 0.85 ms), and regular firing pattern [1st interspike interval ISI) = 91 ms]. 4. Class I stellate neurons differed morphologically from Class I pyramidal neurons only in the size (cross sectional area = 330 microns 2) and stellate appearance of their perikarya. These neurons had characteristic lower input resistance (40.1 M omega), shorter time constant of membrane charging tau 0 (14.5 ms), shorter duration action potential (half-width = 0.7 ms), and a burst firing pattern (1st ISI = 6.0 ms), all of which were statistically different from Class I pyramidal neurons. 5. Class II neurons were multipolar (cross sectional area = 235 microns 2) and were distinguishable from Class I neurons by the almost complete absence of dendritic spines. Class II neurons were characterized electrophysiologically by a midrange input resistance (58 M omega), intermediate time constant of membrane charging tau 0 (19 ms), intermediate action-potential duration (half-width = 0.77 ms), and a burst firing pattern (1st ISI = 6.0 ms). In contrast to Class I neurons, action-potential firing of Class II neurons did not accommodate in response to prolonged depolarizing current injection. 6. In conclusion, BLA neurons may be characterized by their specific electrophysiological properties as well as by their morphological traits. Therefore, permitting assessment of signal transduction in identified populations of neurons within this nucleus. PMID- 8492169 TI - Transient extracellular volume reduction in neural lobe of rat hypophysis in response to neural stalk stimulation in vitro and its relationship to extracellular potassium. AB - 1. Using ion-sensitive microelectrodes, a transient reduction in the local volume of neural lobe extracellular space was found to accompany the elevation in extracellular potassium induced by stimulation of the neural stalk. The volume decrease and potassium increase had similar stimulus-response curves when stimulus frequency was varied from 1 to 40 Hz, with maximal response at 20 Hz. The curves for stimulus duration diverged, as a near maximal potassium response was reached in 4-16 s with a 20-Hz stimulus, while the extracellular volume decrease was maximal at 64 s. 2. The volume decrease, but not the potassium increase, was strongly inhibited by lowering bath temperature and moderately inhibited by furosemide and by lowering extracellular chloride concentration. Both the volume and the potassium response were enhanced by ouabain. 3. In conclusion, shrinkage of the local extracellular space in neural lobe during nerve activity is mediated by a metabolically active process which is only partially dependent upon extracellular chloride concentration and anion-cation co transport, but is relatively independent of Na(+)-K+ pump activity. A transient shrinkage in extracellular space during increased neurohypophysial nerve activity would be expected to play a role in hormone diffusion, ion buffering, and extracellular current flow. PMID- 8492170 TI - A cortical EEG frequency with a REM-specific increase in amplitude. AB - 1. We used period/amplitude (PA) analysis to survey electroencephalography (EEG) across vigilance states in the Sprague-Dawley rat. We found a fast cortical EEG frequency band, which we designate rho, whose wave amplitude in rapid eye movement (REM) was elevated above the levels in both waking and nonrapid eye movement (NREM). Rho wave amplitudes in NREM and waking were similar. 2. Rho occurred between 20 and 30 Hz, which appears to be a transitional range. In the 5 Hz band below rho, EEG wave amplitudes are higher in both NREM and REM than in waking; above 30 Hz, amplitudes are higher in waking and REM than in NREM. The augmented amplitude of rho in REM may result from a unique point of interaction of EEG mechanisms of sleep and waking. 3. In addition to its theoretical interest, rho is of practical value for scoring REM sleep. It could obviate the need to record hippocampal theta EEG, eliminating electrode penetration of the brain and reducing the number of leads required to classify rat vigilance states. PMID- 8492171 TI - Evaluating quality in interventional neuroradiology. PMID- 8492172 TI - Spontaneous calcific cerebral emboli from calcified aortic valve stenosis. AB - Calcific cerebral emboli (CE) are a rare complication of calcified aortic valve stenosis (CAS). These emboli usually result from diagnostic manoeuvres (e.g. left heart catheterization) or from therapeutic procedures (e.g. heart valve surgery). Spontaneous calcific emboli are exceptional. We present the cases of two subjects known to have CAS who presented with acute neurological disorders suggesting strokes. In both subjects CT scans of the skull and brain provided a diagnosis of spontaneous CE by showing calcium-dense dots located on vessels or within the cerebral parenchyma. Additional examinations enabled us to determine the origin (heart or carotid artery) of these emboli. The finding of spontaneous cerebral CE is a very strong argument in favour of surgical valve replacement in these patients. PMID- 8492173 TI - Lambdoid craniosynostosis. A 3D-computerized tomographic approach. AB - From a series of eleven children aged from 4 months to eight years presenting with a parieto-occipital flattening that was unilateral in nine and bilateral in two, we attempted to determine a 3D-CT semeiology able to demonstrate the presence of a lambdoid suture synostosis, as well as the participation of coronal and lambdoid sutures in the genesis of complex cranial malformations. Pure isolated forms of lambdoid synostosis are rare and justify a surgical treatment for cosmetic purposes if the deformation is severe and progressive. PMID- 8492174 TI - Cerebral cavernous angioma. Diagnostic considerations. AB - Eighteen cases of cerebral cavernous angiomas are reported, and their histopathological, clinical and radiological features are reviewed. MR complements TC in characterizing cavernomas and in distinguishing them from similar-appearing lesions. However, when such lesions are seen with atypical features, discrimination from hemorrhagic tumors remains problematic. More malignant lesions present, on MRI, a much larger area of abnormality and make themselves obvious in a shorter period. Gadolinium administration may allow a more specific interpretation of small lesions. PMID- 8492175 TI - Cervical nucleolysis: indications, technique, results. 190 patients. AB - For many years now percutaneous techniques have proved effective in the curative treatment of lumbar disc herniation, mostly in young subjects. This technique, however, is seldom indicated, let alone performed, in the cervical spine for a variety of reasons: a) the neck contains several closely arranged structures such as the vasculo-nervous bundles, the airway-digestive tract and the cervical spine around the spinal cord; b) the disc is approached by the anterior route, in contrast with the lumbo-sacral spine where the approach is posterolateral; c) the manufacturers insist on restrictions in the use of chymopapain in view of the potential risk of spinal cord damage, either by possible breaks in the meninges of by accidental diffusion of the enzyme into perimedullary epidural structures which support a particularly developed venous plexus; d) legal protection may be denied to operators who perform cervical chemonucleolysis, since the product has not yet been officially authorized, in France and perhaps elsewhere*, for treatment of cervical disc herniation. Several years of experience in the practice of cervical nucleolysis have convinced the authors that this method is remarkably effective and can be used in the treatment of cervicobrachial neuralgia (CBN) occurring in young subjects. Radiculalgia is essentially due to a disc fragment being positioned within the vertebral canal or a foramen, thereby compressing the nerve roots. During several years microsurgery of the disc has been effective in the treatment of refractory radiculalgia, and to compete with this procedure familiar to neurosurgeons cervical nucleolysis must convincingly demonstrate that its therapeutic value is at least as good as that of surgery. Finally, the vast majority of cervical disc herniations is made up of free disc fragments located within the meshes of the posterior longitudinal ligament of the spine (transligamentous fragment). Cervical nucleolysis was introduced in France by Bonafe and Lazorthes made enthusiastic by their first studies, and the idea of this procedure, developed by a radio-neurosurgical team, has gradually been gaining ground. The decision to intervene is made when the radiculalgia is recurrent or resistant to a well-conducted medical treatment of several weeks duration. Therefore all disc herniations that would have been treated surgically can be treated by injection of an enzyme. This point is very important, and in fact the well-codified and effective surgical procedure has progressively been abandoned by the operators, in view of the simplicity of nucleolysis and the rapid pain relief it procures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492176 TI - Herniated disk in adolescents. AB - Twenty-one patients (9 female and 12 male) aged from 13 to 22 years were observed for lumbago and lumbo-sciatica caused by a discopathy which was subsequently confirmed by radiology and surgery. None of these patients had a history of trauma. It must be underlined that the painful symptoms exhibited and the young age of the patients suggest such pathologies as infections, tumours or malformations, but the possibility of discopathy must always be considered. It is also interesting to note the differences observed in symptomatology between adults and adolescents and to consider the various pathogenetic factors which might cause discopathy in adolescents while it was until now believed to be reserved to adults. PMID- 8492177 TI - Hallervorden-Spatz syndrome and MRI: the "tiger's eye". One case. AB - The MRI exploration of a woman suspected, on clinical grounds, of having Hallervorden-Spatz disease (or rather syndrome) revealed, on T2-weighted sequences, the "tiger's eye" or "target" image of the pallidum described by previous authors: i.e. a high-intensity signal in the centre of a distinct low intensity signal; it also showed an abnormal low-intensity signal of the substantia nigra. These changes are related to the iron deposits and neuro-axonal lesions which characterize the disease. The MRI semeiology of Hallervorden-Spatz disease has been analyzed in the literature. The images we obtained in this patient with the echo-gradient technique using T1-weighted sequences were unusual, showing a low-intensity signal of the globi pallidi surrounded by central and peripheral low-intensity signal areas, whereas the images obtained with spin-echo T1-weighted sequences were normal. PMID- 8492178 TI - Intracranial dural arteriovenous fistulas and sinus thrombosis. Report of five cases. AB - Dural arteriovenous fistula and sinus thrombosis are sometimes associated. The relationship between these two conditions remains unclear. Thrombophlebitis of the dural sinus may induce a dural fistula. Conversely, thrombophlebitis is sometimes observed in the course of dural fistulas. We report five cases of dural arteriovenous fistulas associated with sinus thrombosis. In three cases, the angiographic and pathological data indicated the responsibility of thrombosis in the occurrence of the fistula. In the others two cases, thrombophlebitis and fistula were simultaneously diagnosed by angiography. However, in one of these cases, the clinical data showed that the fistula probably was a causative factor in the occurrence of thrombophlebitis. PMID- 8492179 TI - Where are the nurses? PMID- 8492180 TI - Collaborative critical care education: the educator link. AB - This article describes the Houston Area Collaborative Critical Care Program that has had 10,406 attendees in 5 years. Eleven collaborating institutions participate in the modular program. Strategies are identified for development, implementation, and evaluation of the program. The educators' dedication to collaboration is essential to the success of this program. PMID- 8492181 TI - Workplace education: adult education in a hospital nursing staff development department. AB - There is limited research-based information about the use of adult education principles in workplace education programs. A case study was conducted in a hospital nursing staff development department to provide recommendations for the current practice of adult education. The instructors used many of the principles of adult education, but problems stemmed from a lack of common understanding of adult education concepts. PMID- 8492182 TI - An orientation for inexperienced educators. AB - For the past several years, an orientation program for novice educators at Long Island College Hospital has had a measure of success. A process was developed to encourage qualified applicants to participate in a program designed to develop their competency in the teaching-learning process. This article describes the strategies used as well as challenges in hiring novice educators. PMID- 8492183 TI - The effect of a competency-based targeted staff development program on nursing productivity. AB - This study is based on the empirical fact that among nurses large variations occur not only in clinical competency but also in individual productivity. The article proposes that competency-based targeted staff development programs can improve productivity as well as nursing performance. Research presented here shows that the nurses on units using targeted staff development increased the time spent on professional and direct care and reduced nonprofessional and indirect care tasks in comparison to nurses on the control nursing unit. PMID- 8492184 TI - Orientation through self-study. AB - Traditional orientation programs and schedules did not meet the needs of new nurses seeking employment at one small hospital. The orientation class content was redesigned into self-study modules. This approach allowed greater flexibility in the start date for orientees, the orientation schedule, and the rate at which the content was covered. PMID- 8492185 TI - Continuing education policy and budgets: a survey of tenets and practice. AB - Continuing education offerings for nurses are essential to ensure competency of staff practicing in a changing health care environment. Fiscal constraint, coupled with staff shortages, has led institutions to examine carefully administrative support for continuing education. This study describes current trends in midwestern institutions' continuing education policy and budget support. Knowledge gained is useful to administrators in education departments who oversee a facility's budget development, to those who administer procedures based on established policy, and to academic settings as they plan outreach continuing education offerings. PMID- 8492186 TI - An effective skin integrity program. AB - Nursing staff development personnel are responsible for increasing the awareness of nursing staff of the problems caused by pressure ulcers and for supplying them with information needed for prevention and treatment. In answer to one hospital's needs, a hospital-wide, nurse-initiated, nurse-managed skin integrity program was developed and instituted. Protocols for treatment were standardized according to the latest concepts in wound healing. Basic components of the program were included in a comprehensive but succinct reference manual available on each nursing unit. Strategies for implementation were carefully planned to include feedback, approval, and support of selected physicians and nurses. Key for an effective, ongoing skin integrity program are the skin integrity clinicians and educated, confident, and enthusiastic staff nurses. Throughout the process of introducing this program, education of various groups of health-care professionals--physicians, staff nurses, skin integrity clinicians--by the Nursing Staff Development Department was pivotal in achieving a relatively smooth implementation of the program. Outcomes have demonstrated the success of this skin integrity program to both patients and staff. Creative planning, diligent research, skillful organization, and credibility of the specialists in the Nursing Staff Development Department were important elements in the development, implementation, and success of this skin integrity program. PMID- 8492187 TI - Outcome studies. PMID- 8492188 TI - HIV-infected women and infants. Social and health factors impeding utilization of health care. AB - The utilization of health care by HIV-seropositive pregnant women and their infants was studied in an indigent urban population. Ninety HIV-seropositive women delivered 99 HIV-exposed infants at the Johns Hopkins Hospital from August 1, 1988, to April 1, 1991. Repeat pregnancies occurred in 17 (18.9%) women during the study period. Completion of the primary immunization series by age nine months was the criteria for infant adherence to medical care. Of all infants, 72.9% achieved adequate immunization status by nine months. However, only 41 (45.6%) women reported ever seeking HIV-related health care. Factors associated with maternal adherence with HIV-related health care included HIV status of her infant, maternal drug use, and incarceration. Number of living children, maternal age, educational level, marital status, and repeat pregnancy were not associated with mothers seeking HIV-related health care. Despite low adherence to HIV related health care in this sample of HIV-seropositive women, the majority of their infants did receive adequate immunizations, one proxy measure of adequate infant health care. PMID- 8492189 TI - Fetal sex preference of second-trimester gravidas. AB - Fetal sex preferences of pregnant women are based on psychological, physiologic, economic, and sociologic factors. Parental responses to the knowledge of fetal/infant sex range from feticide to preferential treatment of the preferred sexed child. This study describes the sex preferences, sex beliefs, attempted sex preselection techniques, and desire to know the fetal sex of 243 second-trimester gravidas. Data demonstrated a willingness to disclose sex preferences, with 81% declaring a preference. The majority of women (81%) also wished to know the sex of their child prior to delivery regardless of their acknowledgment of a sex preference. The results of this survey offer implications for research on the phenomena relating to sex preference. PMID- 8492190 TI - Models of midwifery care. Denmark, Sweden, and The Netherlands. AB - The organization of maternity services in Denmark, Sweden, and the Netherlands was studied under the sponsorship of the World Health Organization European Headquarters Office of Maternal and Child Health. Midwifery care is highly respected and is a central feature of obstetric care in each of these countries. In Denmark and Sweden, almost all births are in the hospital, and autonomous midwives are employed by national health services. About three-quarters of Dutch midwives are in independent practice, and 34% of Dutch women give birth at home. In each country midwives provide "the first line" of care for normal pregnant women and are viewed as essential to the excellent perinatal outcomes these three countries enjoy. PMID- 8492191 TI - Evaluation of research studies. Part IV: Validity and reliability--concepts and application. AB - The concepts of validity and reliability are defined within the context of applied clinical research. Validity concerns what an instrument measures and how well it does so. Reliability concerns the faith that one can have in the data obtained from use of an instrument, that is, the degree to which any measuring tool controls for random error. The researcher selects a measure that demonstrates content, criterion, or construct validity, according to the intended use of the measurement tool. Similarly, the researcher selects a measure that demonstrates a degree of reliability that is needed for its application. It is possible to have reliability without validity, but it is logically impossible to demonstrate that an unreliable test is valid. PMID- 8492192 TI - AIDS. Taking universal precautions seriously. PMID- 8492193 TI - Nurse-midwifery management of women with human immunodeficiency virus disease. AB - Primary care for women with human immunodeficiency virus (HIV) disease is appropriately provided by nurse-midwives within a well-coordinated system of medical consultation and referral. The issues of access to care, partner notification, reproductive choice, and breast-feeding are discussed. The nature of the collaborative management of HIV in pregnancy is explained. Management issues include the effects of HIV infection and pregnancy upon each other, perinatal transmission risks and postpartum needs, family planning, and gynecologic needs. Clinical care guidelines are included. PMID- 8492194 TI - Midwifery care for women with human immunodeficiency virus disease in pregnancy. A demonstration project at the Johns Hopkins Hospital. AB - Nurse-midwives at the Johns Hopkins Hospital, in conjunction with their colleagues in obstetrics, pediatrics, and infectious disease, are participating in a demonstration project designed to provide continuity of care for women with HIV disease in pregnancy. In the past 19 months, 73 women have been enrolled in the project. This article describes how the midwifery model of care has been integrated into the existing system of routine obstetric care and specialized HIV related care at the institution. This project could serve as a model for others who are redesigning health care delivery systems to include more nurse-midwives, especially those who are trying to adapt to an ever-increasing number of women experiencing some phase of HIV disease during their pregnancy. A companion article explains the midwifery and medical protocols used in the project and discusses other clinically relevant issues. PMID- 8492195 TI - Hospital privileges: a matter of proficiency or profitability? PMID- 8492196 TI - Changing methods of preventing infective endocarditis following dental procedures: 1943 to 1993. AB - The report by Northrop and Crowley in the inaugural issue of the Journal of Oral Surgery heralded the appearance of studies designed to confirm both the relationship between dental procedure-induced bacteremia and infective endocarditis and the best methods to interrupt this chain of causation. Their discovery that antibiotics can modulate bacteremias produced by dental procedures eventually led to the universal adoption of the prophylactic regimens to prevent cases of infective endocarditis following dental procedures. Advances since their work have involved a greater understanding of the role of adherence in the mechanism of action of prophylactic antibiotics, an appreciation of the ability to limit antibiotic administration to only the immediate preoperative period, the need to keep prophylactic regimens as uncomplicated as is safe, and greater knowledge about the interaction between dental procedures and bacteremias. Whether the widespread use of prophylactic antibiotics during dental procedures significantly decreases the incidence of endocarditis remains open to future investigation. PMID- 8492197 TI - In vivo deterioration of proplast-teflon temporomandibular joint interpositional implants: a scanning electron microscopic and energy-dispersive X-ray analysis. AB - The surgical treatment of internal derangements of the temporomandibular joint (TMJ) often involves disc removal. Alloplastic interpositional implants for disc replacement have been widely used to avoid the development of osteoarthritic changes in the TMJ. This study reports the in vivo wear characteristics of Proplast-Teflon (Vitek Inc, Houston, TX) interpositional implants (PTIPI) in 12 patients who had their implants for 13 to 71 (mean 54.6 +/- 5.8 SEM) months. In all cases, changes in the condyle and fossa were found resulting from resorption and replacement of the articulating bone by granulomatous tissue. All implants showed significant signs of wear, such as thinning, cracks, and tears, and overt perforations were seen in five cases. Scanning electron microscopy (SEM) combined with energy-dispersive x-ray microanalysis (EDAX) showed numerous microfragments of the PTIPI in the peri-implant soft tissues. Microfragments were demonstrated by their aluminum content. In addition to the inflammatory foreign-body reaction, it is suggested that there also were toxic and hypersensitivity reactions to aluminum involved in the pathogenesis of the bone destruction. PMID- 8492198 TI - Suction drainage in the postsurgical treatment of jaw cysts. AB - Intraoral or extraoral closed suction drainage was used following the surgical enucleation of 42 jaw cysts. Primary healing was observed in 38 (90%) of the patients and complete osseous regeneration was achieved in 17 of 30 patients. In the remaining patients, a slight loss in width and height of the involved area occurred. No functional disturbances were caused by these bony reductions. PMID- 8492199 TI - A comparison of diclofenac with and without single-dose intravenous steroid to prevent postoperative pain after third molar removal. AB - The efficacy of 40 mg of methylprednisolone given intravenously before operation in combination with orally administered rapid-release and sustained-release diclofenac preparations in preventing postoperative pain after third molar removal was studied. The administration of methylprednisolone and diclofenac resulted in greater pain relief than did administration of diclofenac alone. PMID- 8492200 TI - The effect of an ibuprofen-codeine combination for the treatment of patients with pain after removal of lower third molars. AB - A double-blind randomized crossover analgesic trial was carried out on 70 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a two-dose regimen of the combination ibuprofen-codeine, 400 to 60 mg, was compared with ibuprofen, 400 mg. Each of the two doses was taken when the patient needed pain relief and the pain intensity was measured on a visual analog scale during the 10-hour period after the first medication. Because of carryover effects between periods 1 and 2, the analysis was carried out only for period 1 according to a parallel group design. Of the 60 patients who were evaluated for analgesic effect, the mean pain reduction of dose 1 was 63% for the 29 patients given ibuprofen-codeine and 50% for the 31 patients given ibuprofen; the mean duration of effect was 7.5 and 6.3 hours, respectively. The difference in pain reduction index (pain reduction X duration of effect) between the two treatments was significant in favor of the combination, whereas the separate variables of pain reduction and duration of effect were not significantly different. The mean pain reduction was 67% after doses 1 and 2 for patients on ibuprofen-codeine and 52% for those on ibuprofen; the mean duration of effect was 9.4 and 9.2 hours, respectively. For doses 1 and 2, the difference in pain reduction index per dose between the two treatments was significant but not the difference for the separate variables, pain reduction, and duration of effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492201 TI - Salivary duct carcinoma: a report of nine cases. AB - Nine cases of salivary duct carcinoma are presented. Eight lesions were located in the parotid gland and one in the submandibular gland. Tumor size was greater than 3 cm in four cases (44%), and facial paralysis was observed in five tumors (62.5%). Lymph node metastases were observed macroscopically or microscopically in seven patients. Perineural and lymphatic invasion were detected in eight and seven cases, respectively. Free surgical margins were obtained in eight of the nine patients (88%). Adjuvant postoperative irradiation was delivered in eight patients. Five patients died of disease in spite of the different clinicopathologic characteristics and aggressiveness of the surgery and irradiation. None of the parameters studied correlated with the final outcome. PMID- 8492202 TI - The effect of bone morphogenetic protein on osseointegration of titanium implants. AB - This study evaluated the osteointegration of threaded cylindrical uncoated endosseous implants in combination with either bovine bone morphogenetic protein (bBMP) (group 1) or bovine serum albumin (BSA) (group 2) in edentulous dogs. Histologic observations showed that new bone formation was markedly increased by bBMP. The screw-surfaced implants in combination with bBMP exhibited apparent direct bone apposition 4 weeks postimplantation with no evidence of a connective tissue capsule. Thick fibrous connective tissue still encapsulated the control implants, although some new bone was observed slowly growing from the margins of the host bed. Eight weeks after implantation, there was an exact fit between the implant and the bone in group 1, and the surrounding bone was arranged in a regular manner. In group 2, there were still a few areas of thin fibrous tissue surrounding the implants. The results indicate that the rate of osteointegration was increased by bBMP. PMID- 8492203 TI - Changes in the inferior alveolar nerve following mandibular lengthening in the dog using distraction osteogenesis. AB - Distraction osteogenesis as per Ilizarov was used to lengthen the canine mandible. In this study, physiological and ultrastructural examination of the inferior nerve was performed. Mandibular body corticotomies were performed, and the mandible was distracted 7 mm. The animals were killed 4 weeks after the distraction was completed. Bone formed within the distraction gap in all dogs. There was no statistically significant difference in the jaw-jerk voltage between control and experimental sides. There was a significant difference between the distracted and control nerves in only one area of one nerve. PMID- 8492204 TI - Management of Bell's palsy. PMID- 8492205 TI - Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. AB - In a previous article in the Journal of Oral and Maxillofacial Surgery, the initial results of treating 10 patients with solitary, unstable, displaced zygomatic fractures using resorbable poly(L-lactide) (PLLA) plates and screws was reported (Bos et al, 1987). This article describes the long-term results in these patients. Three years postoperatively, four patients returned because they were concerned about an intermittent swelling at the site of implantation. The remaining patients were recalled after the same postoperative period. All patients were examined clinically, and six patients were operated on again for evaluation of the swelling and to investigate the nature of the tissue reaction. The explanted material showed remnants of degraded PLLA surrounded by a dense fibrous capsule. The swelling was classified as a nonspecific foreign body reaction to the degraded PLLA material. Ultrastructural investigation of the degraded material showed an internalization of crystal-like PLLA material in the cytoplasm of various cells. PMID- 8492206 TI - Recurrent enlargement of the left maxillary alveolus. AB - Presented is a case report of osteosarcoma of the maxilla in a patient with Paget's disease. This case is unusual because of recurrent benign soft tissue enlargements at the site of eventual malignant disease. PMID- 8492207 TI - Oral adenoid squamous cell carcinoma: a report of three cases and review of the literature. PMID- 8492208 TI - Oral and facial lesions in Cowden's disease: report of two cases and a review of the literature. PMID- 8492209 TI - Solitary intraosseous neurofibroma of the maxilla: report of a case. PMID- 8492210 TI - Aneurysmal bone cyst mimicking a malignancy. PMID- 8492211 TI - Fracture of the bone-grafted mandible secondary to stress shielding: report of a case and review of the literature. PMID- 8492212 TI - Osteoma of the tongue. PMID- 8492213 TI - Late retrobulbar hemorrhage and blindness following malar fracture complicated by factor XI deficiency. PMID- 8492214 TI - Cherubism: report of an aggressive case and review of the literature. PMID- 8492215 TI - Surgical ciliated cyst: a delayed complication in a case of maxillary orthognathic surgery. PMID- 8492216 TI - Transpalatal rigid fixation of the maxillary sagittal osteotomy in Le Fort I orthognathic surgery. PMID- 8492218 TI - Proper insurance coverage for dentoalveolar surgery. PMID- 8492217 TI - Standards of care are not new. PMID- 8492219 TI - Familial hypertrophic cardiomyopathy. PMID- 8492220 TI - Detection of monoclonality in low-grade B-cell lymphomas using the polymerase chain reaction is dependent on primer selection and lymphoma type. AB - Detection of B-cell monoclonality using the polymerase chain reaction (PCR) promises the quick and cost-effective separation of monoclonal from polyclonal B cell disease. However, the efficiency of the method has yet to be fully assessed, particularly with regard to disease type and selection of PCR primers. We have evaluated two approaches based on amplification of the immunoglobulin heavy chain gene using framework 2 (Fr2) and framework 3 (Fr3) region primers. Frozen tissue samples from 94 cases of low-grade B-cell lymphoma were investigated, all of which had previously been shown to be monoclonal by Southern blot analysis. Using a Fr2 primer, we were able to show monoclonality in 85 per cent of cases; with Fr3, 80 per cent of cases; and using both techniques in separate reactions, 90 per cent of cases. Thus, a significant false-negative rate exists with either primer which can be reduced by using both. We also found a difference in the efficiency of detection in different types of lymphoma; only 87 per cent of mucosa-associated lymphomas and centroblastic/centrocytic lymphomas were shown to be monoclonal, whereas all of the other lymphoma types tested were positive using one or both methods. We conclude that PCR detection of B-cell monoclonality allows rapid analysis of tissue samples, including paraffin-processed material. False-negative results which occur in some types of lymphoma can be reduced by the use of two or more primer combinations. PMID- 8492221 TI - Immunoglobulin heavy chain rearrangements in primary brain lymphomas. A study using PCR to amplify CDR-III. AB - Primary brain lymphomas (PBLs) have only rarely been analysed for immunoglobulin heavy chain (IgH) rearrangements. In this study, DNA was extracted from paraffin blocks in 23 cases of PBL and examined for IgH rearrangements using the polymerase chain reaction (PCR) to amplify the complementarity-determining region III (CDR-III) of rearranged IgH genes. Fifteen of the cases were phenotyped on paraffin-embedded tissue using a pan-B and pan-T antibody (L26 and UCHL-1, respectively). The remaining eight cases were not phenotyped for lack of tissue. For comparison, we used DNA extracted from paraffin blocks of normal brain, lymph nodes with lymphoid hyperplasia, and non-lymphoid malignancies. PCR products were examined by polyacrylamide gel electrophoresis. Among the ten B-cell PBL; four had a pattern indicative of IgH rearrangement, one had a germline pattern, and five had no detectable PCR products. Among the five T-cell PBLs, one had a germline pattern and four had no detectable products. Among the eight untyped PBLs, two had IgH rearrangement, four had a germline pattern, and two gave no detectable products. DNA from non-lymphoid tissues gave a consistent germline pattern, while DNA from polyclonal lymphoid populations (lymph node) had a pattern of polyclonal IgH rearrangement. In a dilution study, a clonal rearrangement could be detected as long as the clone's DNA constituted at least 10 per cent of the total DNA. PCR to amplify CDR-III can be successfully applied to DNA extracted from paraffin blocks, and it detected a clonal rearrangement in 50 per cent of cases that gave a detectable pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492222 TI - Gene rearrangement of bcl-1 and bcl-2 is confined to distinct subgroups of high grade malignant B-cell lymphomas. AB - The occurrence of bcl-1 and bcl-2 gene rearrangements was investigated in 37 cases of high-grade B-cell lymphomas. Bcl-2 rearrangement was detectable only in single cases of primary centroblastic lymphoma with a follicular growth pattern, whereas secondary centroblastic lymphomas evolving from a centroblastic centrocytic lymphoma were positive in up to 60 per cent of the cases analysed. Bcl-1 rearrangement was found only in one case of immunoblastic B-cell lymphoma with a history of pre-existing lymphoplasmacytoid immunocytoma. It is concluded that there may be a subgroup of centroblastic lymphomas with a biology similar to that of centroblastic-centrocytic lymphomas. The detection of bcl-1 rearrangement in high-grade lymphomas may indicate a secondary high-grade lymphoma. PMID- 8492223 TI - A novel monoclonal antibody (FUN-1) identifies an activation antigen in cells of the B-cell lineage and Reed-Sternberg cells. AB - The characterization of a new monoclonal antibody (MoAb) recognizing a human B cell activation antigen, designated FUN-1, is described in this paper. Immunoprecipitation revealed that FUN-1 recognizes an antigen with a molecular weight (MW) of 75kD. FUN-1 reacts with pokeweed mitogen-activated B lymphocytes and monocytes of peripheral blood, but not with unstimulated lymphocytes or granulocytes. It also reacts with large lymphoid cells in germinal centres, Epstein-Barr virus-transformed B cell lines, large B-cell lymphomas, Ki-1 positive anaplastic large-cell lymphomas, and Reed-Sternberg cells of Hodgkin's disease, but not with Concanavalin A-activated T cells, acute lymphoblastic leukaemias, T-cell lymphomas, or low-grade B-cell leukaemias. These findings indicate that FUN-1 recognizes a previously unreported B-cell activation antigen. This MoAb appears to be useful for the study of maturation and differentiation in the B-cell lineage as well as for the immunohistochemical diagnosis of B-cell lymphomas and Hodgkin's disease. PMID- 8492224 TI - Establishment and characterization of a new human clear-cell sarcoma cell-line, HS-MM. AB - We have established and morphologically characterized a new human clear-cell sarcoma cell-line, HS-MM, from the pleural effusion of a 39-year-old man with pulmonary metastasis derived from the primary popliteal tumour. The HS-MM cells were round or spindle-shaped, with round nuclei containing extremely prominent nucleoli. Light microscopically, the heterotransplanted nude mouse tumours showed essentially the same features as those of the original sarcoma, revealing an alveolar pattern of tumour cells with abundant clear cytoplasm. Both in vitro and in vivo, the cells reacted with anti-S-100 protein and melanoma-specific HMB 45 antibodies by immunohistochemistry. Ultrastructurally, the cells contained round euchromatin-rich nuclei with large nucleoli revealing conspicuous nucleolonema, and a large amount of glycogen and a few lysosomal dense bodies, but no premelanosomes in their cytoplasm. The HS-MM cell line was thus fully proven to exhibit the unique characteristics of a clear sarcoma both in vitro and in vivo, being also compatible with an amelanotic melanoma. This cell line will therefore be extremely useful for clinicopathological and histogenetic studies on clear cell sarcomas. PMID- 8492225 TI - Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas. AB - Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-alpha and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-alpha. In sections including normal differentiated oral mucosa, the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus paralleling the situation observed in the normal differentiated oral mucosa. In four cases, material was available from both a primary tumour and a metastasis. Three of these were positive for TGF alpha and EGF with the same staining pattern as that of the primary tumours. This investigation together with our previous results confirms the existence of TGF alpha, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases. PMID- 8492226 TI - Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para adenomatous gland in Cushing's disease and Nelson's syndrome. AB - Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear. PMID- 8492227 TI - Manganese superoxide dismutase content and localization in human thyroid tumours. AB - Manganese-containing superoxide dismutase (Mn-SOD) content and its immunohistochemical localization in human thyroid tumours and some other thyroid diseases were examined and compared with adjacent normal thyroid tissue. Enzyme linked immunosorbent assay (ELISA) was used in this study for the measurement of Mn-SOD. The content of Mn-SOD tended to increase in diffuse hyperplasia, adenomatous goitre, and follicular adenoma. In papillary carcinoma, it was significantly higher than in adjacent normal thyroid tissue. Follicular carcinoma also revealed a markedly high Mn-SOD content. In the immunohistochemical study, adjacent normal thyroid tissue showed granular positive staining of Mn-SOD in the cytoplasm. An increase of Mn-SOD was observed in the papillary proliferative lesion of diffuse hyperplasia and in the follicles adjacent to lymphoid tissue in chronic thyroiditis with hypothyroidism. Strong positive staining of Mn-SOD was observed in papillary and follicular carcinomas, whereas in anaplastic carcinoma staining was markedly less intense. These results indicate that the Mn-SOD content varies according to the degree of differentiation of thyroid carcinomas. PMID- 8492228 TI - Expression of xenobiotic metabolizing enzymes in breast cancer. AB - We have studied the expression of different xenobiotic metabolizing enzymes in primary operable breast cancer of no special type. The expression of two forms of cytochrome P450, microsomal epoxide hydrolase, and three classes of glutathione S transferase was investigated using immunohistochemistry. The tumours were characterized by consistent expression of microsomal epoxide hydrolase and by variable expression of the two forms of cytochrome P450 and the three types of glutathione S-transferase. Cytochrome P450 1A and cytochrome P450 3A were identified in 39 and 22 per cent of tumours, respectively. In each case, immunostaining was present only in areas of invasive carcinoma. Epoxide hydrolase was identified in 89 per cent of tumours and glutathione S-transferases pi, mu, and alpha were identified in 56, 65, and 44 per cent of tumours, respectively. Immunoreactivity for epoxide hydrolase and glutathione S-transferases was identified in both tumours and non-neoplastic breast tissue. The presence of different xenobiotic metabolizing enzymes may have a role in determining the intrinsic drug resistance of breast cancer to a variety of anti-cancer drugs, and the expression of these enzymes can readily be assessed using immunohistochemistry. PMID- 8492229 TI - The expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in 'gastric metaplasia' of the proximal duodenum: implications for the nature of 'gastric metaplasia'. AB - Expression of pS2 protein (an oestrogen-induced gene discovered in the MCF-7 breast carcinoma cell line) and its homologue human spasmolytic polypeptide (hSP) was analysed, using immunohistochemistry and in situ hybridization to their mRNAs, in the proximal duodenum of 17 partial gastrectomy specimens removed from individuals with chronic peptic ulceration. Eight were found to have gastric-type metaplasia. In gastric metaplasia, mRNAs for pS2 and hSP, and pS2 peptide antibody were co-localized in the cells covering the duodenal villi. pS2 immunostaining was diffusely cytoplasmic in nature. A similar pattern was seen in Brunner's gland ducts. The trefoil peptide localization in gastric metaplasia closely resembles that seen in superficial gastric epithelium and the distal Brunner's gland duct, which in turn shares morphological similarities with gastric epithelium. We therefore conclude that gastric metaplasia may be the result of an expansion of the surface component of the Brunner's gland duct. The function of these trefoil peptides is at present unknown, but their distribution elsewhere suggests an involvement in reparative mechanisms. The similarities between gastric foveolar and Brunner's gland duct epithelium may derive from common restitution-enhancing features pertinent to a locally harsh environment. PMID- 8492230 TI - Cartilage and bone formation in repairing Achilles tendons within diffusion chambers: evidence for tendon-cartilage and cartilage-bone conversion in vivo. AB - Rodent Achilles tendons were subjected to midpoint tenotomy and allowed to recover for various times in situ before the operated tissue was removed, placed into a Millipore diffusion chamber, and inserted intraperitoneally into syngeneic hosts. Diffusion chambers were then removed at weekly intervals, such that the total time after the operation (i.e., time allowed to recover in situ plus time within the diffusion chamber) was up to 8 weeks, and examined histologically. Ectopic cartilage was produced within the diffusion chamber after a total of 4 weeks but only if the first 2 weeks of recovery were in situ. With increasing time, calcified cartilage, osteoid, and bone were also observed. Overall, the evidence suggests that the cartilage forms via a direct conversion from tendon tissue and that the bone may form as a result of differentiative changes of hypertrophic chondrocytes. PMID- 8492231 TI - A simple technique for the measurement of fractal dimensions in histopathological specimens. AB - A computer program has been devised which enables a simple method for the fractal dimension analysis of histological or cytological material to be performed rapidly with relatively inexpensive hardware. The fractal dimension of a structure refers to its self-similarity over a range of scales and appears to be well suited to histopathological preparations. Thus, the fine 'roughness' of object profiles can be assessed more appropriately by this technique than by means of conventional Euclidean geometry. Images of the object(s) to be investigated are firstly digitized after presentation to a high-performance computer via a video camera or a graphics tablet system and then analysed using the computer program, which has its basis in a standard perimeter estimate method. It is proposed that such techniques may find extensive use in investigative and diagnostic histopathology. PMID- 8492232 TI - A psychosocial summary flow sheet: facilitating the coordination of care, enhancing the quality of care. AB - To improve the continuity of care and to better coordinate psychosocial care, the Psychosocial Oncology Program at the Ontario Cancer Institute/Princess Margaret Hospital developed a psychosocial summary flow sheet. The objectives of the pilot project evaluation were: (a) to examine preparation to use the flow sheet prior to its implementation, (b) to gather information on how staff used the flow sheet, and (c) to determine how its design and implementation could be improved. The charts of all the patients on the units participating in the pilot project were examined and a questionnaire was sent to all staff involved with patient care on these units. The results of the evaluation indicated that the psychosocial summary flow sheet was perceived to be an asset to psychosocial care and could be implemented hospital-wide. Based on the evaluation, a number of changes were made in its design and a strategy for hospital-wide implementation was planned. PMID- 8492233 TI - Assessment of upper gastrointestinal motility in the cancer-associated dyspepsia syndrome. AB - Cancer patients experience many gastrointestinal symptoms which may lead to weight loss. Assessment of gastrointestinal motility may contribute to our understanding of these symptoms and suggest rational therapeutic approaches to the anorexia-cachexia syndrome. We have evaluated a simple, inexpensive, well tolerated test of upper gastrointestinal motility in patients with advanced cancer. One-centimetre portions of radiopaque nasogastric tubing were ingested with food. Six hours later, a flat-plate abdominal x-ray was obtained to determine the marker placement. Patients were evaluated for gastrointestinal symptoms. Those with more symptoms, particularly early satiety, had a greater incidence of reduced upper gastrointestinal motility. PMID- 8492234 TI - A handful of sugar onto the fire? PMID- 8492235 TI - Vancouver General Hospital Palliative Care Unit utilization review. AB - This paper describes the utilization pattern in the Palliative Care Unit at Vancouver General Hospital for a six-month period (1 April-30 September 1991) and relates the information provided to the mandate of the palliative care program. It is a retrospective study of 139 patients discharged during this period. Data were collected from the Hospital Medical Records Institute (HMRI), the Medical Records Department of Vancouver General Hospital, patients' charts, the palliative care unit admission/discharge book, and palliative care consultation statistics. PMID- 8492236 TI - High-tech, aggressive palliative care: in the service of quality of life. AB - The hospice movement grew in part as a reaction to the perception that modern medical care had become too technological at the expense of being impersonal and insensitive to human psychological and spiritual concerns. In the United States, the institutionalization of hospice care under Medicare and other reimbursement systems has further established hospice as an alternative to high-technology, high-cost care. The present paper examines the question: What if hospice care becomes itself high-technology, aggressive, costly health care in order to remain true to its goal of maximizing quality of life? Implications for the goals and philosophical underpinnings of palliative care are discussed. PMID- 8492237 TI - Which antiemetic? AB - The choice of antiemetic should not be arbitrary, but should be based on knowledge of the different pathways of the various stimuli that lead to nausea and vomiting and the neuroreceptors involved. The steps to be taken in choosing an appropriate antiemetic are described. They are (a) to establish the probable cause of the nausea and vomiting, (b) to consider the afferent pathways involved, (c) to define the neuroreceptors activated at each of these sites, (d) to select the group of antiemetics that antagonizes these neuroreceptors, and (e) to choose the most potent antiemetic with the fewest side effects in that group. Causes for failure to respond to a chosen antiemetic are considered and the action to be taken is described. PMID- 8492238 TI - The family in hospital-based home care with special reference to terminally ill cancer patients. AB - Eighty-seven next of kin, 80 spouses and seven adult children, were the primary caregivers of terminally ill patients (87% cancer patients) cared for at the hospital-based home care (HBHC) unit of Motala Hospital during 1989-1990. All of the patients died in their homes. Next of kin were asked to complete self questionnaires and to give written comments on their experiences and their perception of how the patient had felt about 13 aspects of home care provided by the HBHC staff. The response rate was 94%. In nine out of 13 areas, such as adequate information at the time of referral about the HBHC, security, support, immediate extra help when needed, high quality of nursing, and care and pain control, 86%-97% of next of kin were very satisfied (7-9 on a 9-point scale); whereas information provided about the disease, economic support, and support given after death were very satisfactory according to 72%, 58%, and 80% of relatives, respectively. Gender and time from diagnosis to death did not seem to affect responses. Next of kin of cancer patients were generally more satisfied than next of kin of other terminally ill patients. A total time of care of more than 60 days (median time) was associated with significantly more positive responses. Older spouses were significantly more satisfied with the HBHC than younger ones; despite this, 99% of all next of kin would choose HBHC again in a similar situation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492239 TI - The photo repair of pyrimidine dimers by DNA photolyase and model systems. AB - Pyrimidine dimers are eliminated from DNA by a number of different mechanisms known as DNA repair. Photoreactivation, the reversal of the harmful effects of short wavelength radiation by subsequent exposure to longer wavelengths, is one such mechanism. In photoreactivation, the enzyme DNA photolyase utilises light in order to catalyse the cleavage of the cyclobutane ring of the pyrimidine dimer. The results of recent studies of E. coli DNA photolyase and model systems using techniques such as steady state and flash photolysis, time resolved fluorescence and photo CIDNP are surveyed. A mechanism is proposed for the in vitro reaction of E. coli DNA photolyase which involves photoreduction of the FAD radical cofactor followed by electron donation to the dimer from the excited singlet state of reduced FAD. PMID- 8492240 TI - HIV-1 promoter activation following an oxidative stress mediated by singlet oxygen. AB - Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (1O2) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since 1O2 fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular DNA of epithelial cells, can be transactivated following an oxidative stress mediated by 1O2. In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of 1O2 generated intracellularly. An extracellular generation of 1O2 can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome. PMID- 8492241 TI - Molecular mechanism of drug photosensitization. 4. Photohemolysis sensitized by carprofen. AB - Red blood cell lysis photosensitized by carprofen (CPF) was investigated. The photohemolysis process was observed in both aerobic and anaerobic conditions. Irradiation (310-390 nm) of buffered CPF solutions at pH 7.4 in deaerated conditions leads to a dehalogenation process via intermediate radicals with formation of the compound 2-(2-carbazolyl)propanoic acid (I) in the presence of hydrogen donors. Irradiation of I produces decarboxylation via free radicals and the formation of a stable decarboxylated compound, 2-ethylcarbazole (II). The photodegradation products I and II do not show lytic activity. The dechlorinated product I shows photosensitizing ability which was studied in the presence of the red blood cells in both aerated and deaerated solution. When carried out in the presence of additives, the observed photohemolysis suggests the involvement of free radicals and singlet oxygen in the membrane damage induced by both CPF and photoproduct I irradiation, whereas there is no evidence of any role for hydroxyl radicals. Superoxide anion is involved only in the photosensitization process induced by photoproduct I. PMID- 8492242 TI - Repair of the two diastereoisomer photoadducts formed between 7-methylpyrido(3,4 c)psoralen (MePyPs) and thymidine in yeast cells: a chemical approach. AB - When analysing the repair of psoralen plus UVA-induced photoadducts in DNA, it must be realized that, in most cases, different isomers are formed. The monofunctional psoralen derivative 7-methylpyrido(3,4-c)psoralen (MePyPs) is known for its high antiproliferative activity at the cellular level and interesting photochemotherapeutic properties. To understand its photobiological efficiency in more detail, the induction of specific photoadducts in DNA and their repair were analysed in a eukaryotic cell system, the yeast Saccharomyces cerevisiae. After photoaddition of MePyPs, two main diastereoisomers were characterized after enzymatic hydrolysis of the DNA and analysis by high performance liquid chromatography. One diastereoisomer was more effectively repaired in yeast than the other during post-treatment incubation, suggesting that the two diastereoisomers may be recognized differently by cellular enzymatic repair systems. PMID- 8492243 TI - Furan-side pyridopsoralens monoadducts to the thymine moiety of DNA. AB - Isolation of the main cycloadducts formed in DNA by the UV-A (ultraviolet light of class A) photoreaction of 7-methyl-pyrido[3,4-c]psoralen (MePyPs) and 7-methyl pyrido[4,3- c]psoralen (2N-MePyPs) was achieved by HPLC separation subsequent to enzymatic hydrolysis of DNA. The photoadducts have been quantified and their chemical structure assigned on the basis of spectroscopic measurements, including absorption and fluorescence spectroscopy, and circular dichroism as well as mass spectrometry analysis. They all present characteristics which are consistent with furan-side monoadducts resulting from a C4-cycloaddition of the psoralens to thymidine. The two major MePyPs-thymidine monoadducts formed in DNA exhibit a diastereoisomeric relationship and are likely to have a cis-syn stereochemistry. PMID- 8492245 TI - Thiols as potential UV radiation protectors: an in vitro study. AB - The following thiols were investigated with regard to their possible UV-radiation protective properties: captopril, cysteamine, ergothioneine, mesna, mercaptopropionylglycine, N-acetylcysteine, and penicillamine. As a measure for protection, the inhibition of in vitro irreversible photobinding of the labeled phototoxic drugs chlorpromazine (CPZ) and 8-methoxypsoralen (8-MOP) to protein and DNA was used. Besides photobinding to biomacromolecules, the photodegradation of CPZ and the formation of promazine (PZH) and hydroxypromazine (PZOH) were measured as well. Because of the H-atom and electron donating capacity of the thiols, the ratio [PZOH]/[PZH] was expected to be decreased and the photodegradation of CPZ was expected to be higher in the presence of thiols. Maximum inhibition of CPZ photobinding ranged for the different thiols between 21 100% (DNA) and 17-87% (human serum albumin). All thiols enhanced the photodegradation of CPZ (19-84%) and inhibited the ratio [PZOH]/[PZH] (90-97%). 8 MOP photobinding to human serum albumin was also clearly inhibited (75-96%), but remarkably less to DNA (2-41%). This study indicates that thiols are able to cope with a variety of reactive species. Scavenging of radicals, quenching of singlet molecular oxygen species and reaction with excited states seem to be essential mechanisms involved with this process. PMID- 8492244 TI - Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine. AB - The effects of exogenous delta-aminolevulinic acid (ALA) on cultured PAM 212 cells were investigated. PAM cells exposed to ALA produce an excess of products of the heme biosynthesis pathway within hours. The endogenous porphyrins render the cells photosensitive in a time-, ALA dose- and irradiation-dependent manner. Independently of the ALA-induced photosensitized processes, ALA itself reduces the proliferation rate of PAM cells during the exponential growth phase. Iron deprivation by addition of the chelating agent desferrioxamine (df) accelerates the photosensitizing process, and thus makes it more efficient at lower ALA concentrations. The effects of df were compared with the effects of manganese-df and iron-df. The results indicate that iron trapping is the most important factor for the potentiation of ALA-stimulated photodynamic sensitization as well as for the dark toxicity. Iron complexing agents may thus be used to optimize ALA effects in the photodynamic treatment of cutaneous neoplasms with endogenous porphyrins. PMID- 8492246 TI - Muscle fiber formation in vitro is delayed by low power laser irradiation. AB - The myogenic cell culture provides a good in vitro model for studying the differentiation process of the muscle tissue. Although the growth of the mononucleated myoblasts is predetermined, in that they will fuse to form multinucleated muscle fibers, some control on the process of fusion can be achieved in vitro. The low power laser irradiation (LPLI) has been shown to enhance in cultured mammalian cells DNA synthesis and motility of cells. In our rat myogenic cell line (L8) system the LPLI induced a delay of 5 to 6 hours in the onset of fusion of the myoblasts compared to the nonirradiated cells. The creatine kinase activity and the incorporation of labelled thymidine of the irradiated cultures were similar to the pattern of behaviour of these parameters in the control cultures. Thus, we have extended the longevity of the myoblasts population. We assume that the delay in fusion was induced by the increase of the motility of the myoblasts in culture, so that rearrangements of physical contacts or of membrane components were needed to resume fusion. PMID- 8492247 TI - Assessment of vitamin K status of the newborn infant. AB - This article reviews our current knowledge of the assessment of vitamin K status in the human infant, where a deficiency state has been described. Laboratory measures for the functional assessment of vitamin K-dependent coagulation factors as well as the quantitative assay for vitamin K1 (phylloquinone) are reviewed. In addition, four different methods of measuring abnormal prothrombin, a protein induced by vitamin K absence (PIVKA-II), and its use in clinical pediatrics are discussed. Finally, additional methods are briefly described for assessing vitamin K status, including serum osteocalcin, urinary excretion of gamma carboxyglutamic acid, and deficiencies of the enzymes necessary for the regeneration of phylloquinone in the so-called vitamin K cycle. PMID- 8492248 TI - Examining the role of inflammatory cytokines in chronic inflammatory bowel disease. PMID- 8492249 TI - Tumor necrosis factor and IL-1 beta expression in pediatric patients with inflammatory bowel disease. AB - The local release of inflammatory mediators are intricately linked with initiation and propagation of the inflammatory reaction in ulcerative colitis (UC) and Crohn's disease. We have used immunohistochemical staining of colonic biopsies to determine the cell of origin and the location of the cells which synthesize of TNF-alpha and IL-1 beta in patients with UC and Crohn's colitis. Patients were chosen from children aged 7-16 years, who had UC or Crohn's diagnosed following review of colonic biopsies taken during colonoscopy. The patients reviewed had not received treatment for inflammatory bowel disease. Paraffin embedded colonic biopsies were sectioned, deparaffinized, and stained with mouse monoclonal IgG antibodies directed against human recombinant TNF-alpha and IL-1 beta. The colonic lamina propria of all biopsies from patients with UC or Crohn's colitis was expanded with a mixed mononuclear, polymorphonuclear, lymphocytic, and plasmacytic infiltrate. Mononuclear cells distributed throughout the interstitium, stained prominently for both TNF-alpha and IL-1 beta. Plasmacytes, polymorphonuclear leukocytes, small lymphocytes, and foamy macrophages did not stain for either TNF-alpha or IL-1 beta. Transmigrating mononuclear cells in crypt epithelium also stained brightly for both TNF-alpha and IL-1 beta. Colonic epithelial cells did not stain for either TNF-alpha or IL 1 beta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492250 TI - Serodiagnosis of Helicobacter pylori infection in children by an indirect immunofluorescence test. AB - The objective of this study was to evaluate the accuracy of an indirect immunofluorescence (IIF) test for serodiagnosis of Helicobacter pylori infection in children and to determine how the test is affected by the presence of antibodies against Campylobacter jejuni. We studied 65 consecutive children (two with endoscopically confirmed duodenal ulcer) and a series of 18 children with duodenal ulcer. Thirty children were H. pylori negative, as determined by culture, by the preformed urease test, and by carbolfuchsin-stained smears. The microorganism was identified by microbiological methods in 35 of the 65 (53.85%) consecutive patients studied and in all children with duodenal ulcer. The titer of the IIF test was > or = 1:20 in the sera of all children with duodenal ulcer and in the sera of 30 of 33 H. pylori-positive children without duodenal ulcer. No H. pylori-negative children had titers > 1:10. A serum dilution of 1:20 discriminated between H. pylori-infected and noninfected children. Absorption with C. jejuni did not change the levels of IgG against H. pylori. When five patients who had been successfully treated with metronidazole, amoxycillin, and furazolidone for 7 days were retested, a slight decrease in anti-H. pylori IgG levels was noted from the third month on. The decrease was more significant 9 months after the eradication of the microorganism. PMID- 8492251 TI - The prevalence of Helicobacter pylori-positive serology in asymptomatic children. AB - Epidemiologic data are presented about the prevalence of Helicobacter pylori positivity as determined by serology in a large series of asymptomatic children (n = 466). Serology is now generally accepted as a valid noninvasive screening method for the detection of Helicobacter pylori infection. Blood samples were taken from 466 apparently healthy children (ages 2-14 years) who were admitted to our pediatric 1-day clinic for elective surgery. The children originated from different ethnic backgrounds. All were born in Belgium and have been living there ever since. Thirty-four (7.3%) had positive titers for Helicobacter pylori. There was a significant increase in the number of positive patients with advancing age (5.4% in the age group 2-8 years and 13.4% in the age group 8-14 years; p < 0.001). We also found a significant difference in the prevalence of Helicobacter pylori positivity between Caucasian Belgian children and non-Caucasian children of different ethnic backgrounds. This relatively high prevalence of positive serology in asymptomatic older children (13.4%) should be considered in studies on the incidence or causative role of Helicobacter pylori in children with chronic abdominal complaints. PMID- 8492252 TI - Anderson's disease: no linkage to the apo B locus. AB - We describe three patients with Anderson's disease who are members of one family; the father and mother are close relatives and three of seven children show symptoms of the disease. All patients suffered from diarrhea, failure to thrive, and recurrent infections during infancy. Although these symptoms disappeared later in life, biochemical disorders (such as low plasma levels of apolipoproteins A1 and B and cholesterol, resulting in avitaminosis E, plus failure to secrete chylomicrons after a fat meal) persisted. Electron microscopy of enterocytes of one of the patients showed accumulation of lipid vacuoles with no significant aberration of the Golgi apparatus itself. It is possible, therefore, that the disease reflects a defect in chylomicron assembly. We found that low levels of apolipoprotein (apo) B48 were present in the patients' plasma. This suggests that the processing of the B100 message resulting in apo B48 functions normally. The possibility that a mutation in the apo B gene results in an abnormal apo B48 protein is very unlikely since a variable number tandem repeat (VNTR) polymorphism probe mapped to chromosome 2 failed to show correspondence of the parent alleles with the disease. These observations confirm the suggestion that Anderson's disease is not linked to the apo B locus. PMID- 8492253 TI - Down's syndrome and celiac disease: the prevalence of high IgA-antigliadin antibodies and HLA-DR and DQ antigens in trisomy 21. AB - Patients with Down's syndrome (DS) or celiac disease (CD) have altered immune systems. Autoimmune diseases have been described in both conditions; the coexistence of DS and CD has been occasionally reported, but a clear relationship has not been definitely established. In this study we determined IgA antigliadin antibodies (IgA-AGA) in 155 children with DS, and the results were compared with those of the control groups formed by 320 children affected by upper-respiratory tract infections and 115 children with gastrointestinal symptoms but with normal jejunal mucosa. High IgA-AGA levels were found in 26% of DS patients, in 1% of the first control group and in 10% of the second control group. Such differences are statistically significant. Twenty-one DS patients with high IgA-AGA levels and gastrointestinal symptoms underwent jejunal biopsy, and total villous atrophy was found in seven of them (33.33%). HLA-DR and -DQ antigens were also determined in 75 DS patients (20 with high and 55 with normal IgA-AGA levels), and the percentages of the different phenotypes were compared in the two groups and with those of a control group. No statistically significant difference was found, but DR3, DR7, and DQ2 alleles were always present in DS patients with jejunal atrophy. Our study confirms the data reported in the literature about higher levels of IgA-AGA in DS patients and the relatively high incidence of CD in this group of patients. PMID- 8492254 TI - Transmission electron microscopy of microvilli of intestinal epithelial cells in celiac disease in remission and transient gluten enteropathy in children after a gluten-free diet. AB - The structure of microvilli of intestinal epithelial cells was investigated in 70 children: 34 with celiac disease in remission, 28 with transient gluten enteropathy after a gluten-free diet, and eight controls. Transmission electron microscopy was used to determine the mean thickness of the glycocalyx layer covering the microvilli, the mean length and width of microvilli, and the number of microvilli per 1 micron length of enterocyte surface. The structure of the glycocalyx was found to be intact, but in some children with treated celiac disease the layer of glycocalyx was either thin or absent on the surface of individual cell microvilli. In children with treated celiac disease, microvilli were statistically significantly shorter than those in children with transient gluten enteropathy and controls. Microvillous width in treated celiac disease was greater as compared with that in controls. There was no difference in the number of microvilli on the enterocyte surface in the three groups. PMID- 8492255 TI - Upper gastrointestinal endoscopy in recurrent abdominal pain of childhood. AB - Over a 2.5-year period, 82 consecutive children complaining of recurrent abdominal pain underwent upper gastrointestinal endoscopy. Gastroscopy confirmed pathology in 48 of the children (58.5%). Four of the children, who also had undergone gastroscopy, had other diagnoses (lactose malabsorption, hydronephrosis, yersiniosis), and 30 of the children (36.6%) retained the initial diagnosis of recurrent abdominal pain syndrome. Gastritis was found in 48 of the children, 18 of whom (37.5%) had positive test results for Helicobacter pylori, based on histology and/or culture. Of 16 H. pylori-positive children tested, 12 (75%) also had an elevated concentration of IgG-class antibodies to H. pylori in their sera. Three of the children had duodenal ulcer disease, all of whom were H. pylori positive. Esophagitis was found in eight of the children with gastritis, all of whom were found to have gastroesophageal reflux. Our data suggest that among the children with recurrent abdominal pain syndrome, organic pathology is more common than was previously thought. Altogether 22% of the children with recurrent abdominal pain syndrome were infected with H. pylori. PMID- 8492256 TI - Bicarbonate and citrate in oral rehydration therapy: studies in a model of secretory diarrhea. AB - In situ perfusion of the rat jejunum and ileum was used to study the effect of inclusion of bicarbonate or citrate on the ability of four oral rehydration solutions to promote small-intestinal absorption of water and sodium. Solutions varied in their sodium (60-90 mM) and glucose (111-140 mM) content and osmolality (281-331 mosmol/kg). They were studied before and after exclusion of base both in normal intestine and in secreting intestine after exposure to cholera toxin. All solutions promoted net water absorption in the normal intestine and reversed net water secretion to absorption in the cholera toxin-treated intestine to varying degrees. Net sodium movement was directly related to the sodium content of oral rehydration solutions. Inclusion of bicarbonate or citrate did not promote significantly greater absorption of water or sodium than did solutions without base, in normal or secreting intestine. In the secreting intestine, inclusion of bicarbonate in two solutions actually resulted in greater sodium secretion than did identical solutions from which bicarbonate was omitted. These studies suggest that the inclusion of base or base precursors in oral rehydration solutions to enhance water and sodium absorption is unjustified in both normal and secreting small intestine. PMID- 8492257 TI - Pancreatic function and congenital duodenal anomalies. AB - Six children operated on for congenital anomalies of the duodenum were investigated to find out if pancreatic dysfunction was associated with the duodenal malformation, even in the absence of clinical evidence of pancreatic insufficiency. None of the children had diarrhea and none requested nutritional support. Pancreatic function was assessed by enzyme activities (lipase, trypsin, and chymotrypsin) bicarbonate and calcium measurements in pancreatic juice obtained through a nasoduodenal tube under stimulation by secretin and cerulein. Results showed no significant modification in hydro-electrolytic secretion, but impairment of enzymatic secretion was seen. The physiopathological relationship between duodenal anomalies and pancreatic dysfunction is discussed. PMID- 8492258 TI - Induction of exocrine pancreas maturation at weaning in young developing pigs. AB - The influence of weaning, at either 4 or 6 weeks of age, on the maturation of the exocrine pancreas was studied in naturally reared Swedish Landrace pigs that had no access to solid food. The pigs were surgically fitted with chronic catheters at 3 weeks of age, permitting periodic sampling of pancreatic juice and blood in conscious animals < or = 4 weeks after weaning. During the suckling period, pancreatic fluid and enzyme secretion remained low, both before (preprandial) and after (postprandial) milk ingestion. After weaning at 4 or 6 weeks of age, juice secretion, output of total protein, and levels of different hydrolases (amylase, trypsin, lipase, and carboxylester lipase) and the cofactor colipase all increased markedly postprandially. Moreover, after weaning, the plasma insulin level increased postprandially. This did not happen before weaning, although blood glucose levels always rose after feeding. The data showed a relationship between the time of weaning and the induction of exocrine pancreatic maturation in pigs. This finding implies that postnatal development of pancreatic function is triggered by the dietary change from sow milk to dry solid food. In contrast, the age of the pig appears to be of minor importance, since weaning at either 4 or 6 weeks of age gave a similar result. PMID- 8492259 TI - Increased in vitro intestinal permeability in suckling rats exposed to cow milk during lactation. AB - Specific mucosal barrier functions of the gut develop in the newborn to combat the constant challenge of foreign antigens. To determine whether exposure to cow milk antigens interferes with this maturational process, jejunal permeability to macromolecules and the activation of immune mechanisms were studied in preweaning rats. At the age of 14 days, rat pups were divided into three feeding groups. Controls (n = 18) remained on normal maternal milk; group CM (n = 27) additionally received a daily gavage feed of cow milk; and in group D (n = 23), cow milk was given to dams. At 21 days, when "gut closure" normally occurs, intestinal in vitro absorption of horseradish peroxidase in its intact form was significantly higher in group CM and in group D than in controls (F = 5.6; p = 0.006): group CM: mean, 37.8 ng/h/cm2; 95% confidence interval (CI), 19.4-73.6; group D: mean, 26.9 ng/h/cm2; 95% CI, 8.2-88.2; controls: mean, 4.0 ng/h/cm2; 95% CI, 1.2-13.9. In association with increased jejunal permeability, there was enhanced jejunal eosinophilic infiltration in group CM. In group D, the number of specific antibody-secreting cells in peripheral blood against beta-lactoglobulin was significantly higher than in group CM and controls. These data indicate that there is a critical period in development when feeding cow milk antigens delays gut closure. They further suggest that mucosal barrier function is impaired due to a local hypersensitivity reaction to cow milk antigens, irrespective of the protection of maternal milk or maternal antigen processing. PMID- 8492260 TI - Evaluation of a daily dose of 25 micrograms vitamin K1 to prevent vitamin K deficiency in breast-fed infants. AB - Vitamin K prophylaxis is recommended to prevent the hazard of hemorrhage caused by vitamin K deficiency in young infants. A single administration after birth seems inadequate to completely prevent late haemorrhagic disease in breast-fed infants. The preventive effect of a daily oral dose of 25 micrograms vitamin K1, which is comparable to about half the dose ingested by formula-fed infants, was evaluated in 58 breast-fed infants. No clinical or biochemical signs of vitamin K deficiency occurred; PIVKA-II was not detectable, and vitamin K1 concentrations were moderately elevated. Vitamin K1 levels were negatively correlated with the number of hours elapsed since the most recent gift. Twenty to 28 h after the administration, median (P10-P90) levels were 1,262 (267-4,328), 1,072 (293 3,427), and 882 (329-2,070) pg/ml at 4, 8, and 12 weeks of age, respectively. Vitamin K1 levels in formula-fed infants (n = 10) were around 7,000 pg/ml. In conclusion, daily supplementation of 25 micrograms vitamin K1 can be recommended for breast-fed infants to prevent vitamin K deficiency beyond the neonatal period. PMID- 8492261 TI - Postmenstrual age correlates to indices of protein metabolism in very low birth weight infants. AB - In 14 infants who were normal in weight for gestational age and 14 infants who were small for gestational age, the plasma essential amino acid profiles and serum urea concentrations were studied between the 30th and 46th weeks of postmenstrual age. All infants were of very low birth weight (< 1,500 g) and were fed with fresh human milk fortified with 6 g freeze-dried human milk per 100 ml (mean protein intake 3.1 g/kg/day, mean energy intake 130 kcal/kg/day). With the exception of threonine, all measured plasma essential amino acid concentrations increased significantly with increasing postmenstrual age (appropriate for gestational age infants: r = 0.861, p < 0.01; small for gestational age infants: r = 0.772, p < 0.001). No differences in this increase could be found between the infants who were small or appropriate for gestational age. The serum urea concentrations also increased with increasing postmenstrual age without differences between the study groups (appropriate for gestational age infants: r = 0.658, p < 0.01; small for gestational age infants: r = 0.604, p < 0.05). The results indicate that very low birth weight infants of similar weights may have very different protein requirements, depending on their postmenstrual ages. Thus, postmenstrual age is of greater importance than birth weight when protein nutrition is planned for very low birth weight infants. PMID- 8492262 TI - Continuation of breast-feeding in an Israeli population. AB - Demographic and perinatal factors were analyzed in an Israeli urban community to determine the rates of continuation of breast-feeding and the factors influencing these rates. For the purpose of this study, breast-feeding was defined as occurring if infants received at least one breast-feed during a 24-h period. Among 633 mothers initiating breast-feeding, 40.3% completed 3 months of breast feeding. The factors significantly associated with the continuation of breast feeding were maternal religious belief, high education level, high parity, and previous breast-feeding success. Multivariate analysis by stepwise logistic regression showed that orthodox religious belief was the most significant associated factor. A third interview undertaken after 12 months among the 165 mothers who successfully completed 3 months of breast feeding showed declines of breast-feeding at the second (31.5%), third (53.1%), and fourth (60.4%) trimesters. Only 12.7% of this population completed 12 months of breast-feeding. Again, the mothers' religious beliefs and education levels were significantly related to the continuation of breast-feeding. Each specific community must be analyzed to find those groups of mothers at risk for early weaning from breast feeding. PMID- 8492263 TI - An open triple crossover study comparing water absorption from potable water, Lucozade, and Dioralyte using the stable isotope 18O. AB - Nine volunteer children aged 6-9 years were randomised in a Latin square design to receive one of three oral solutions [Lucozade (Beechams), Dioralyte (Rorer Pharmaceuticals), and potable water] labeled with the stable isotope 18O. After administration, breath CO2 was collected using a face mask for a period of 120 min. Mass spectrometric analysis gave the enrichments of 18O in CO2 at parts per million levels. Analysis showed the accumulation of the tracer (and, by inference, absorption from the gut) to be quickest from Dioralyte and slowest from Lucozade. We hope to use this technique to investigate the absorption of water from oral rehydration solutions in infants with dehydration due to gastroenteritis. PMID- 8492264 TI - HBV infection in pediatric liver transplantation. AB - When hepatitis B virus (HBV) infection precedes orthotopic liver transplantation (OLT), an important issue is to avoid post-OLT HBV infection of the transplanted liver. When HBV infection is found after OLT, the main objective is to prevent the complication of cirrhosis. A study of HBV infection in 162 liver-transplanted children followed at Hopital de Bicetre is presented here. One hundred forty-one of these children were completely vaccinated against HBV; 89% of them still disposed of protective titers of serum antibodies to hepatitis B surface antigen (anti-HBs) (> 10 IU/L) 6-60 months after OLT. Four children had a HBV-associated liver disease that required OLT. In these children a passive immunoprophylaxis maintaining serum anti-HBs levels > 100 IU/L allowed three of them to remain free of serum hepatitis B surface antigen (HBsAg) and HBV-DNA during follow-up at 10, 20, and 36 months. Four other children have been found to be HBsAg+ after OLT, but it was not clear whether the source of HBV was a reactivation or a de novo infection. Low doses of cyclosporin and prednisone were administered, in order to avoid the complications of HBV infection. Liver needle biopsies in three of these patients 37, 42, and 46 months after OLT showed a moderate chronic active hepatitis and mild fibrosis. Immunostaining for HBs and hepatitis B core (HBc) antigens indicated active viral replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492265 TI - Idiopathic late hemorrhagic disease of newborn and conjugated hyperbilirubinemia. PMID- 8492266 TI - Intramural duodenal hematoma: an unusual complication of duodenal biopsy sampling. PMID- 8492267 TI - Carcinoma of the stomach in a child. PMID- 8492268 TI - Acute pancreatitis in Crohn's disease due to 5-ASA therapy. PMID- 8492269 TI - Is intestinal permeability really a genetic marker for Crohn's disease? PMID- 8492270 TI - Influences on collaborative activities among psychologists and pediatricians: implications for practice, training, and research. AB - Addresses the need for a comprehensive framework that describes the broad range of professional interactions between psychologists and pediatricians, presents a generic model of influences or collaboration and proposes specific implications for training, practice, and research. Three primary influences on the development of collaborative activities are proposed: (a) participants' beliefs about the need for and expectations of the potential outcomes of collaboration; (b) participants' knowledge, skills, and prior experiences, especially in collaborative work; and (c) setting-based barriers and supports. Interventions that promote positive beliefs and expectations among colleagues concerning interdisciplinary work, facilitate specific skills related to cooperative research and management of clinical problems, and develop new practice settings should enhance collaboration. PMID- 8492271 TI - Children's understanding of AIDS: implications for preventive interventions. PMID- 8492272 TI - Developmental progression in children's knowledge of AIDS: implications for education and attitudinal change. AB - The effectiveness of curricula designed to enhance a child's understanding of AIDS may hinge partially upon incorporating information adjusted to the child's developmental status. Accordingly, we examined the developmental progression of children's understanding of illness transmission in general and AIDS in particular, as well as explored the relation between a child's knowledge of AIDS and his/her attitudes toward persons with AIDS. Knowledge of AIDS was manipulated through use of a brief educational intervention. Results support a developmental progression in knowledge about AIDS that is consistent with progressions related to illnesses in general. Knowledge enhancement was associated with positive changes in attitude. PMID- 8492273 TI - Children's perceptions of ill peers as a function of illness conceptualization and attributions of responsibility: AIDS as a paradigm. AB - Assessed the impact of developmental level of illness conceptualization and degree of assigned responsibility on children's reactions to ill peers. Accounts of hypothetical peers were manipulated in a multivariate design with three levels of Disease Label (AIDS vs. cystic fibrosis vs. no label) and two levels of Responsibility Information (low responsibility vs. no responsibility information), with the children's conceptualizations as a continuous variable. Subjects receiving information that the peer was not responsible for the illness tended to endorse higher ratings of acceptance than those receiving no information about illness responsibility. Accounts of peers with AIDS resulted in lower ratings of acceptance than those presented with accounts of peers with cystic fibrosis or an unlabeled illness. Subjects obtaining higher illness conceptualization scores tended to perceive less vulnerability to casual contagion. PMID- 8492274 TI - Developmental and family correlates of children's knowledge and attitudes regarding AIDS. AB - Assessed developmental and family variables associated with children's knowledge of and emotional attitudes toward AIDS. Participants included 65 first to sixth graders from two private elementary schools and their mothers. Between-groups comparisons showed that children knowledgeable about AIDS were older and had more mature illness concepts than children who were not knowledgeable. Among children who were knowledgeable about AIDS, a relatively negative attitude toward AIDS was associated with a negative attitude toward illness in general. Moreover, the children's attitude toward AIDS was more negative than their attitudes toward other serious illnesses. Family relations and maternal AIDS-related knowledge and attitudes were linked with neither children's knowledge nor their attitudes. PMID- 8492276 TI - Pediatric psychologists' perceptions of their work settings. AB - Describes the results of a survey of pediatric psychologists' perceptions of their work settings. Respondents (n = 261) described heterogeneous work settings, professional activities, expectations for workload and administrative arrangements. Clinical activities were prominent, accounting for nearly half the respondents' time. Respondents generally reported high levels of overall satisfaction with their work environments. Highest ranked sources of satisfaction included professional autonomy, patient care, and relationships with colleagues. Highest ranked sources of dissatisfaction included lack of time for research, salary, and patient care workload. Pediatric psychologists in private practice reported higher work satisfaction than those in other settings. Findings have implications for the work-related functioning of pediatric psychologists that should be addressed in research and professional activity. PMID- 8492275 TI - Parents' contributions to knowledge and attitudes regarding AIDS. AB - Examined, in a sample of 170 students in Grades 1-12, relationships between parental background and socialization variables and children's knowledge of AIDS risk factors and willingness to interact with people who have AIDS. Most parents had talked to their children about AIDS and supported early AIDS education, but were susceptible to common transmission myths. Age was the strongest predictor of a child's knowledge and attitudes, but parent ethnicity, education, and occupational status also contributed. Moreover, consistent with a "potentiation" model of socialization, parent knowledge of common transmission myths predicted child knowledge of those same myths only when parent-child communication about AIDS was relatively frequent. PMID- 8492277 TI - Improvements in cognitive performance for schoolchildren in Zaire, Africa, following an iron supplement and treatment for intestinal parasites. AB - Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children (K-ABC) adopted to the language of Kituba. Within a day of this test, each child was evaluated for blood hemoglobin (Hgb) level and the presence of intestinal parasites. Half of the children received an iron supplement (20 mg Fe) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were randomly selected to receive either a vermifuge treatment or placebo. All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment. Using discriminant analysis, performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb resulted in the successful classification of 74% in terms whether a child had received both iron supplement and vermifuge treatment (p = .007). With respect to our home evaluation for each child, factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability. However, the present findings also suggest that over the short-term, changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability, perhaps by means of heightened attentional capacity. PMID- 8492279 TI - School-based health centers. PMID- 8492278 TI - Adolescent substance use during pregnancy. AB - Substance use during pregnancy may be a key mediator of the association between adolescent childbearing and poor newborn outcome. Substance use during pregnancy was evaluated for 50 teens who were consecutive patients at an inner-city university clinic. Although teens reported typical lifetime rates of substance use, self-reports and two urine assays indicated minimal substance use throughout pregnancy. Findings suggest that the adolescents exercised judicious decision making in light of the known health risks of substance use during pregnancy. PMID- 8492280 TI - Teenage smoking: a major health care problem. PMID- 8492281 TI - Monitoring the fat and cholesterol intake of children and adolescents. AB - Nurse practitioners and other health care providers play vital roles in the health education of their clients. A health professional should be able to understand the interplay of diet, education, and exercise in a healthy existence. This article reviews the recommendations offered by the National Cholesterol Education Program (1991) on testing and managing cholesterol levels in children and adolescents. The program recommends a strategy combining two complementary approaches: a population approach and an individual approach. By evaluating these approaches, the timing and rationale for lowering fat and cholesterol are discussed and recommendations are made to health care providers about identifying children at risk. Health care providers should work to promote a physically conscious generation that is well-versed in health maintenance, to identify "high risk" individuals, and to update their own knowledge of national recommendations for managing fat and cholesterol levels in their clients' diets. PMID- 8492282 TI - Gastroesophageal reflux in infancy: review and update. AB - Gastroesophageal reflux is a common occurrence in infancy. The purpose of this article is to describe gastroesophageal reflux and differentiate among its three categories. Initial evaluation includes an accurate history and growth assessment. Continued monitoring of growth is important to determine when and if intervention is necessary. The nurse practitioner will be able to make referrals or prescribe treatment based on the guidelines presented. Having knowledge of the various aspects of this problem will enable the nurse practitioner to assess and monitor the infant and reassure parents. PMID- 8492283 TI - Bibliotherapy as an adjunct to stimulant medication in the treatment of attention deficit hyperactivity disorder. AB - The effectiveness of bibliotherapy as an adjunct to stimulant medication in the treatment of children with attention-deficit hyperactivity disorder was investigated. Subjects were randomly assigned to the experimental group, or the control group. Parents in the experimental group received a written protocol (bibliotherapy) outlining behavioral techniques for managing oppositional child behavior. Results indicated significant differences favoring the experimental group on standardized measures of the intensity of behavior problems in the home, parental knowledge of behavioral principles, and teacher ratings of behavior. This bibliotherapy approach appears to offer an inexpensive adjunct to stimulant medication in the treatment of attention-deficit hyperactivity disorder when individual or group behavior management training is not feasible. PMID- 8492284 TI - Inhalant addiction. PMID- 8492285 TI - Daytime incontinence. PMID- 8492286 TI - Tuberculosis: a reemerging and alarming public health problem. PMID- 8492287 TI - Teen pregnancy and teen parenting. PMID- 8492288 TI - NAPNAP position statement. Corporal punishment. PMID- 8492289 TI - [Reactions and interactions of drugs]. PMID- 8492290 TI - Polarographic and potentiometric investigation of Co(II) complexes with 5 hydroxytryptophan. AB - The formation of the complexes between Co(II) and 5-hydroxytryptophan has been studied by means of polarographic and potentiometric methods. The real stability constants of mono and bis-chelato complexes of Co(II) with 5-hydroxytryptophan, obtained by polarographic method, in Britton-Robinson buffer were found to be, log beta 1 = 4.98 and log beta 2 = 8.45. By applying the potentiometric method, in aqueous medium of ionic strength mu = 0.2, the stability constants, log beta 1 = 4.42 and log beta 2 = 8.57 were obtained. The complexes defined by polarographic method have been used in a purpose of analytical determination of 5 hydroxytryptophan. PMID- 8492291 TI - [Hyperlipemias and hypolipemic agents]. AB - Hyperlipidaemia, as a primary atherogenic risk factor, represents a major problem of public health. This review first reminds the main steps of lipoprotein metabolism, the classification of the most frequent hyperlipidaemias, the objectives of the treatment and the required initial evaluation allowing to decide how to manage the patient. Thereafter, it describes all the available treatments, more particularly the characteristics of the various lipid lowering drugs. Finally, it proposes a step by step strategy for the treatment of the main hyperlipidaemias and summarizes the managements of some particular cases. PMID- 8492292 TI - [Control of membrane permeabilities in mammalian cells and its application to pharmaco-biology]. AB - The plasma membrane in mammalian cells possesses unique permeability properties serving as a selective permeability barrier as well as transporters for nutrients and ions in maintaining cellular homeostasis. External ATP modulates the permeability barrier in transformed cells. The characteristics and possible mechanism for this permeability change are summarized. Application of this membrane change for cancer chemotherapy was also examined in both in vitro and in vivo. The uptake of D-glucose by mammalian cells was carried out by a facilitated diffusion through a specific transporter protein in the membrane. The control mechanism for glucose transport by growth factors based on the changes in the glucose transporter levels is summarized. Modulation of glycosylation in the transporter protein and its possible role are discussed. PMID- 8492293 TI - [Synthetic studies on highly modified nucleosides directed towards creation of anti-HIV agents]. AB - Recent studies on the synthesis of highly modified nucleosides, especially carbocyclic nucleosides, aiming at creating anti-HIV agents have been reviewed. The review includes new methods for the synthesis of carbocyclic C-nucleosides and carbocyclic N-nucleosides including carbocyclic oxetanocin and its analogues developed in our laboratory. Among the carbocyclic nucleosides synthesized, 9-(c 4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine (BCA) showed significant anti-HIV activity. PMID- 8492294 TI - [Qualitative and quantitative analysis of bioactive principles in Zingiberis Rhizoma by means of high performance liquid chromatography and gas liquid chromatography. On the evaluation of Zingiberis Rhizoma and chemical change of constituents during Zingiberis Rhizoma processing]. AB - As a continuing study on the evaluation of various Zingiberis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for 6, 8, 10-gingerol (1, 2, 3), 6,8 shogaol (4, 5), 6-dehydrogingerdione (6), and galanolactone (7) has been developed. By the use of this HPLC method, the contents of these compound in twenty kinds of Zingiberis Rhizoma [originating in China, Taiwan, Vietnam, and Japan (Shizuoka Prefecture)] and fresh ginger root cultivated in Shizuoka Prefecture were examined. It was found that Japanese Zingiberis Rhizoma and fresh ginger root contained 6-gingerol (1), 6-dehydrogingerdione (6), and galanolactone (7) as major constituents, whereas 7 was not detected in imported Zingiberis Rhizoma and 6 was detected in Vietnamese Zingiberis Rhizoma. Furthermore, the contents of 1 and 7 in fresh ginger root decreased remarkably during the processing procedure for Zingiberis Rhizoma. In addition, anti-ulcer sesquiterpene constituents in seven kinds of Zingiberis Rhizoma were analyzed by means of gas liquid chromatography (GLC). PMID- 8492295 TI - [Quantitative analysis of deacylgymnemic acid by high-performance liquid chromatography]. AB - A method of the quantitative analysis was established for the determination of deacylgymnemic acid (DAGA) in the alkaline hydrolysate of the sample containing gymnemic acids which are ingredients of Gymnema sylvestre R. BR. leaves, by means of high-performance liquid chromatography. This method was used for comparing the contents of gymnemic acids in various samples. The amount of gymnemic acids analyzed as DAGA in 70% ethanol extract of dry leaves was about twice that in hot water extract. The commercial health-supplemental foods of five companies were investigated for the contents of gymnemic acids as DAGA and there were large differences from 38 to 251 mg in the dosage per day recommended by each company. PMID- 8492296 TI - [Comparison of bioavailability of salbutamol between oral and rectal administration in rabbits]. AB - In order to obtain a basic knowledge for developing the rectal dosage form of salbutamol (SB), a comparison of the bioavailability was made between oral and rectal administrations. After the intravenous, oral and rectal dosing of SB solution in rabbits, SB and its glucuronide (SBG) in plasma and urine were determined. The bioavailability estimated by the area under the blood concentration-time curve (AUC) of SB from 0 to 9 h after oral and rectal administrations were 1.1 +/- 0.5% and 7.8 +/- 2.2% (mean +/- S. E., n = 5), respectively. Percent of dose excreted in urine as total SB (SB+SBG) 10 h after oral and rectal administrations were 77.3 +/- 3.82% and 9.80 +/- 0.15% (mean +/- S. E., n = 3), respectively, which indicating relatively good oral and poor rectal SB absorption. A partial avoidance of first-pass-effects might contribute to higher bioavailability after the rectal administration. PMID- 8492297 TI - [Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin]. AB - Anti-inflammatory activities of quercitrin (Qu) were studied using various experimental models in mice, rats and guinea pigs. Qu (50, 100 and 200 mg/kg, p.o.) inhibited the rat hind paw edema induced by various phlogistics (carrageenin, dextran, histamine, serotonin and bradykinin) in a dose-dependent manner, and 200 mg/kg of this compound also inhibited the scald edema induced by hot water (54 degrees C). Qu did not show any significant inhibition of the ultraviolet light-induced erythema in guinea-pigs and of the increase of vascular permeability induced by acetic acid in mice. Qu did not affect the granuloma formation in a cotton pellet and the development of adjuvant arthritis in rats. These results indicate that Qu might have an inhibitory effect on acute inflammation. PMID- 8492299 TI - Studies on the interaction of furan with hepatic cytochrome P-450. AB - In vitro incubation of rat liver microsomes with [14C]-furan in the presence of NADPH resulted in the covalent incorporation of furan-derived radioactivity in microsomal protein. Compared to microsomes from untreated rats a two- to threefold increase in binding was observed with microsomes from phenobarbital treated rats and a four- to five-fold increase was observed with microsomes from rats pretreated with imidazole or pyrazole. Covalent binding was reduced with microsomes from rats pretreated with beta-naphthoflavone. Chemicals containing an amine group (semi-carbazide), those in which the amine group is blocked but have a free thiol group (N-acetylcysteine), and those which have both an amine and a thiol group (glutathione) effectively blocked binding of [14C]-furan to microsomal protein. A decrease in cytochrome P-450 (P-450) content and decreases in the activities of P-450-dependent aniline hydroxylase, 7-ethoxycoumarin-O deethylase (ECD), and 7-ethoxyresorufin-O-deethylase (ERD) was observed 24 hours after a single oral administration of 8 or 25 mg/kg of furan, suggesting that the reactive intermediate formed during P-450 catalyzed metabolism could be binding with nucleophilic groups within the P-450. In vitro studies indicated a significant decrease in the activity of aniline hydroxylase in pyrazole microsomes and ECD in phenobarbital microsomes without any significant change in the CO-binding spectrum of P-450 or in the total microsomal heme content, suggesting that furan inhibits the P-450s induced by PB and pyrazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492298 TI - [Pharmacological studies on small peptide fraction derived from soybean. The effects of small peptide fraction derived from soybean on fatigue, obesity and glycemia in mice]. AB - The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia. PMID- 8492300 TI - Interactions in vitro of some organophosphoramidates with neuropathy target esterase and acetylcholinesterase of hen brain. AB - For organophosphates or phosphonates to initiate delayed neuropathy two steps are necessary: (1) progressive covalent reaction with neuropathy target esterase (NTE) to produce a form of inhibited NTE which can be reactivated by incubation with aqueous potassium fluoride (KF) and (2) progressive "aging" of inhibited NTE to a form which can no longer be reactivated by KF. However, it has been shown recently that certain N-unsubstituted organophosphoro-monoamidates (analogues of methamidophos) cause delayed neuropathy even though the inhibited NTE appeared not to have aged (Johnson et al. (1991). Arch. Toxicol., 65, 618-624). In order to study the generality of this phenomenon, we have examined some N-substituted compounds. We report in vitro studies of inhibition and reactivation and aging of both NTE and acetylcholinesterase (AChE) prior to toxicological tests. All the compounds studied were less inhibitory to both NTE and AChE in concentrated rather than in dilute suspensions of EDTA-washed brain particles without added cofactors. There was an apparent disposal of up to 100 mumoles of test compound by particles from 95 mg hen brain, which is far greater than can be explained by covalent binding. The activity is distinct from calcium-dependent "A" esterase. Several N-alkyl phosphoromonoamidates were found to be potent and selective inhibitors of NTE: second-order rate constant for O-n-pentyl N benzylphosphoramido-fluoridate (Cmpd 6) = 5.6 x 10(7) M-1 min-1 at 37 degrees, which is about 100x higher than for acetylcholinesterase (AChE). Inhibited NTE and AChE from several chiral phosphoromono-amidates did not reactivate spontaneously (21 hours at 37 degrees). Virtually 100% reactivation by KF of AChE inhibited by phosphoromonoamidates was achieved at all times tested. Acetylcholinesterase inhibited by 2,5-dichlorophenyl N,N'-di-n butylphosphorodiamidate was 42-56% reactivated by incubation with KF (192 mM in pH 5.2 buffer for 30 minutes at 37 degrees). We believe this is the first report of reactivation of any enzyme after inhibition by a phosphorodiamidate. For NTE inhibited by tabun (O-ethyl N-dimethylphosphoroamidocyanidate), virtually complete and rapid aging (t1/2 = 5.5-8.4 minutes) was observed. Consistent but only partial reactivation by KF was achieved 2 or more hours after inhibition of NTE by Cmpd 6 or by its 2,6-difluoro-analogue (Cmpd 7). However, a small but significant aging (approximately 15-20% loss of reactivatability) was measured soon after a 1 minute inhibition by Cmpd 7, but no further change occurred in 21 hours.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492301 TI - The role of metals in the enzymatic and nonenzymatic oxidation of epinephrine. AB - The effects of transition metals on nonenzymatic and ceruloplasmin catalyzed epinephrine oxidation were investigated by studying rates of epinephrine oxidation in purified buffers and in the presence of metal chelating agents. We found that epinephrine does not "autoxidize" in sodium chloride solutions prepared with deionized water that was further purified by chromatography over Chelex 100 resin prior to use. Epinephrine was oxidized rapidly in sodium chloride prepared with tap water (1.20 +/- 0.12 nmoles/min) or in deionized water (0.40 +/- 0.80 nmoles/min), but this oxidation was prevented by the addition of Desferal, a potent metal chelating agent. Epinephrine oxidation was enhanced upon the addition of ceruloplasmin, and this oxidation rate could be slowed, but not eliminated, by the addition of Desferal. If epinephrine solutions were preincubated for 72 hours with Desferal prior to ceruloplasmin addition, however, no oxidation was observed. Epinephrine was shown to form colored complexes with both iron and copper at pH 7.0. The Fe(III)-epinephrine complex was much more stable than was the Cu(II)-epinephrine complex. Oxygen consumption studies of ceruloplasmin catalyzed epinephrine oxidation showed that copper was a better promoter of epinephrine oxidation than was iron, suggesting that ceruloplasmin catalyzed epinephrine oxidation results from adventitious copper bound to the purified enzyme. In light of these results, the physiological relevance of ceruloplasmin catalyzed oxidation of biogenic amines may be minor. PMID- 8492302 TI - A chaperone-mimetic effect of serum albumin on rhodanese. AB - Reactivation of denatured rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) was found to be aided by the presence of serum albumin. Both the rate and the extent of reactivation of the urea-denatured enzyme were optimal at low rhodanese and moderate serum albumin concentrations. Similarly, stabilization of the sulfurtransferase activity of rhodanese that had been partially unfolded at 40 degrees C was aided by the presence of serum albumin. All the observations are in accord with a model in which enzyme that has been partially refolded from the urea-denatured state or partially unfolded thermally interacts directly with serum albumin in a way that prevents rhodanese self-association. Serum albumin thus acts as a molecular chaperone in these systems. PMID- 8492303 TI - Differential cellular effects in the toxicity of haloalkene and haloalkane cysteine conjugates to rabbit renal proximal tubules. AB - The relationship between the covalent binding, uptake, and toxicity produced by S (1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) was investigated in suspensions of rabbit renal proximal tubules (RPT). The DCVC and TFEC at concentrations of 25 microM produced a time-dependent (1-6 hours) loss of RPT viability. The TFEC was biotransformed rapidly by beta-lyase to a reactive metabolite which bound covalently to tubular protein. Approximately 63% of the TFEC-equivalents inside the cell were bound to protein. Covalent binding of TFEC-equivalents was associated with a 30% decrease in tubular basal and state 3 respiration, a sevenfold increase in lipid peroxidation, and, ultimately, cell death. The DCVC was biotransformed rapidly to a reactive metabolite which bound covalently to tubular protein. Approximately 90% of the DCVC-equivalents inside the cell were bound covalently to tubular protein. Following exposure to 25 microM DCVC, the binding of DCVC-equivalents was associated with a 17-fold increase in lipid peroxidation but, in contrast to TFEC, had no effect on tubular respiration. However, exposure of RPT to 100 microM DCVC resulted in a ninefold increase in the binding of DCVC-equivalents and a 30% decrease in tubular state 3 respiration. The beta-lyase inhibitor aminooxyacetic acid (AOAA) blocked the covalent binding, mitochondrial dysfunction, lipid peroxidation, and cell death produced by TFEC. The AOAA decreased the covalent binding and the lipid peroxidation produced by DCVC by approximately 60-70% but had no effect on cell death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492304 TI - Na+, K+, Cl- cotransport and its regulation in Ehrlich ascites tumor cells. Ca2+/calmodulin and protein kinase C dependent pathways. AB - Net Cl- uptake as well as unidirectional 36Cl influx during regulatory volume increase (RVI) require external K+. Half-maximal rate of bumetanide-sensitive 36Cl uptake is attained at about 3.3 mM external K+. The bumetanide-sensitive K+ influx found during RVI is strongly dependent on both Na+ and Cl-. The bumetanide sensitive unidirectional Na+ influx during RVI is dependent on K+ as well as on Cl-. The cotransporter activated during RVI in Ehrlich cells, therefore, seems to transport Na+, K+ and Cl-. In the presence of ouabain and Ba+ the stoichiometry of the bumetanide-sensitive net fluxes can be measured at 1.0 Na+, 0.8 K+, 2.0 Cl or approximately 1:Na, 1:K, 2:Cl. Under these circumstances the K+ and Cl- flux ratios (influx/efflux) for the bumetanide-sensitive component were estimated at 1.34 +/- 0.08 and 1.82 +/- 0.15 which should be compared to the gradient for the Na+, K+, 2Cl- cotransport system at 1.75 +/- 0.24. Addition of sucrose to hypertonicity causes the Ehrlich cells to shrink with no signs of RVI, whereas shrinkage with hypertonic standard medium (all extracellular ion concentrations increased) results in a RVI response towards the original cell volume. Under both conditions a bumetanide-sensitive unidirectional K+ influx is activated. During hypotonic conditions a small bumetanide-sensitive K+ influx is observed, indicating that the cotransport system is already activated. The cotransport is activated 10-15 fold by bradykinin, an agonist which stimulates phospholipase C resulting in release of internal Ca2+ and activation of protein kinase C. The anti-calmodulin drug pimozide inhibits most of the bumetanide-sensitive K+ influx during RVI. The cotransporter can be activated by the phorbol ester TPA. These results indicate that the stimulation of the Na+, K+, Cl- cotransport involves both Ca2+/calmodulin and protein kinase C. PMID- 8492305 TI - An inwardly rectifying potassium channel in the basolateral membrane of sheep parotid secretory cells. AB - Using whole-cell patch-clamp techniques, we demonstrate that sheep parotid secretory cells have both inwardly and outwardly rectifying currents. The outwardly rectifying current, which is blocked by 10 mmol/liter tetraethylammonium (TEA) applied extracellularly, is probably carried by the 250 pS Ca(2+)- and voltage-activated K+ (BK) channel which has been described in previous studies. In contrast, the inwardly rectifying current, which is also carried by K+ ions, is not sensitive to TEA. It is similar to the inwardly rectifying currents observed in many excitable tissues in that (i) its conductance is dependent on the square root of the extracellular K+, (ii) the voltage range over which it is activated is influenced by the extracellular K+ concentration and (iii) it is blocked by the addition of Cs+ ions (670 mumol/liter) to the bathing solution. Our previously published cell-attached patch studies have shown that the channel type most commonly observed in the basolateral membrane of unstimulated sheep parotid secretory cells is a K+ channel with a conductance of 30 pS and, in this study, we find that its conductance also depends on the square root of the extracellular K+ concentration. It thus seems likely that it carries the inwardly rectifying K+ current seen in the whole-cell studies. PMID- 8492306 TI - Gating and conductance in an outward-rectifying K+ channel from the plasma membrane of Saccharomyces cerevisiae. AB - The plasma membrane of the yeast Saccharomyces cerevisiae has been investigated by patch-clamp techniques, focusing upon the most conspicuous ion channel in that membrane, a K(+)-selective channel. In simple observations on inside-out patches, the channel is predominantly closed at negative membrane voltages, but opens upon polarization towards positive voltages, typically displaying long flickery openings of several hundred milliseconds, separated by long gaps (G). Elevating cytoplasmic calcium shortens the gaps but also introduces brief blocks (B, closures of 2-3 msec duration). On the assumption that the flickery open intervals constitute bursts of very brief openings and closings, below the time resolution of the recording system, analysis via the beta distribution revealed typical closed durations (interrupts, I) near 0.3 msec, and similar open durations. Overall behavior of the channel is most simply described by a kinetic model with a single open state (O), and three parallel closed states with significantly different lifetimes: long (G), short (B) and very short (I). Detailed kinetic analysis of the three open/closed transitions, particularly with varied membrane voltage and cytoplasmic calcium concentration, yielded the following stability constants for channel closure: K1 = 3.3 x e-zu in which u = eVm/kT is the reduced membrane voltage, and z is the charge number; KG = 1.9 x 10(-4) ([Ca2+].ezu)-1; and KB = 2.7 x 10(3)([Ca2+].ezu)2. Because of the antagonistic effects of both membrane voltage (Vm) and cytoplasmic calcium concentration ([Ca2+]cyt) on channel opening from the B state, compared with openings from the G state, plots of net open probability (Po) vs. either Vm or [Ca2+] are bell-shaped, approaching unity at low calcium (microM) and high voltage (+150 mV), and approaching 0.25 at high calcium (10 mM) and zero voltage. Current-voltage curves of the open channel are sigmoid vs. membrane voltage, saturating at large positive or large negative voltages; but time-averaged currents, along the rising limb of Po (in the range 0 to +150 mV, for 10 microM [Ca2+]) make this channel a strong outward rectifier. The overall properties of the channel suggest that it functions in balancing charge movements during secondary active transport in Saccharomyces. PMID- 8492307 TI - A comparison of K+ channel characteristics in human T cells: perforated-patch versus whole-cell recording techniques. AB - Standard whole-cell records using the patch-clamp technique are obtained after rupturing the cell membrane just below the patch pipette. Inherent problems, such as the disruption of cellular architecture and the displacement of cytosol, are unavoidable. In the present report, a whole-cell recording technique which makes use of a monovalent cation ionophore, nystatin, was applied to lymphocytes. Nystatin-perforated patches allow electrical access to the cell interior while virtually blocking the diffusion of cellular constituents into the electrode. By comparing standard whole-cell and perforated-patch techniques we observed marked differences in: activation, inactivation, and deactivation kinetics; steady-state inactivation; and the conductance-voltage relationship of K+ currents in activated human T cells. PMID- 8492308 TI - Regulation by cell volume of Na(+)-K(+)-2Cl- cotransport in vascular endothelial cells: role of protein phosphorylation. AB - Na(+)-K(+)-2Cl- cotransport in aortic endothelial cells is activated by cell shrinkage, inhibited by cell swelling, and is responsible for recovery of cell volume. The role of protein phosphorylation in the regulation of cotransport was examined with two inhibitors of protein phosphatases, okadaic acid and calyculin, and a protein kinase inhibitor, K252a. Both phosphatase inhibitors stimulated cotransport in isotonic medium, with calyculin, a more potent inhibitor of protein phosphatase I, being 50-fold more potent. Neither agent stimulated cotransport in hypertonic medium. Stimulation by calyculin was immediate and was complete by 5 min, with no change in cell Na + K content, indicating that the stimulation of cotransport was not secondary to cell shrinkage. The time required for calyculin to activate cotransport was longer in swollen cells than in normal cells, indicating that the phosphorylation step is affected by cell volume. Activation of cotransport when cells in isotonic medium were placed in hypertonic medium was more rapid than the inactivation of cotransport when cells in hypertonic medium were placed in isotonic medium, which is consistent with a shrinkage-activated kinase rather than a shrinkage-inhibited phosphatase. K252a, a nonspecific protein kinase inhibitor, reduced cotransport in both isotonic and hypertonic media. The rate of inactivation was the same in either medium, indicating that dephosphorylation is not regulated by cell volume. These results demonstrate that Na(+)-K(+)-2Cl- cotransport is activated by protein phosphorylation and is inactivated by a Type I protein phosphatase. The regulation of cotransport by volume is due to changes in the rate of phosphorylation rather than dephosphorylation, suggesting the existence of a volume-sensitive protein kinase. Both the kinase and the phosphatase are constitutively active, perhaps to allow for rapid changes in cotransport activity. PMID- 8492310 TI - Breast cancer risk estimation: a translational statistic for communication to the public. PMID- 8492309 TI - Alterations in a voltage-gated K+ current during the differentiation of ML-1 human myeloblastic leukemia cells. AB - A voltage-gated K+ current has been identified in ML-1 human myeloid leukemia cells, with the use of the whole-cell patch-clamp technique. ML-1 cells proliferate in tissue culture as immature myeloblasts and can be induced to differentiate to nonproliferative monocyte/macrophages. In the myeloblastic cells, activation of the K+ current occurs upon depolarization of the membrane potential to above -40 mV; inactivation of this current is also voltage dependent and follows a simple exponential time course with a time constant (Ti) of 900 msec at 0 mV. The current is inhibited by 4-aminopyridine (IC50 of 80 microM at 0 mV), but is much less sensitive to tetraethylammonium of Ba2+. In cells exposed to the differentiation-inducer 12-O-tetradecanoylphorbol-13-acetate (TPA), dramatic alterations in the K+ current occur: upon exposure to 10 nM TPA during whole-cell recording, the amplitude of the voltage-activated current initially increases (within 4 min) and later decreases (at approximately 30-50 min). Upon addition of 0.5 nM TPA to cells in tissue culture, the current shows suppressed activation and accelerated inactivation in the early stages of differentiation (10-fold decrease in Ti at approximately 7 hr) and is completely suppressed in the later stages (3 days). Thus, this voltage-gated K+ current is suppressed early in the induction of differentiation and associated loss of proliferation in myeloid ML-1 cells exposed to TPA; this parallels the fact that channels of a similar type are activated upon the stimulation of proliferation in lymphoid cells exposed to mitogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492311 TI - Vaccines may help debunk secrets of cancer. PMID- 8492312 TI - GM-CSF vital to some new vaccines. PMID- 8492313 TI - Are endogenous retroviruses inborn agents of cancer? PMID- 8492314 TI - When the side effect helps the treatment: graft-versus-tumor. PMID- 8492315 TI - Cancer in developing countries: opportunity and challenge. AB - Epidemiologic observations indicate that environment and lifestyle are the major determinants of the geographical patterns of cancer. The developing countries, which account for 75% of the world's population, have lower incidence rates of cancer compared with the industrialized nations but bear more than half the global cancer burden. Demographic trends resulting from economic progress (decreasing incidence of infectious diseases, population growth, aging, and urbanization), coupled with increased tobacco consumption and dietary changes, indicate that developing countries will bear a continually increasing proportion of the world's cancer burden and its accompanying demand for the provision of costly treatment programs. Yet the developing countries command only 5% of the world's economic resources, and health care programs are already fully extended and frequently inadequate. Thus, cancer control in the developing countries, including preemptive prevention of the anticipated increases in cancers presently more common in the industrialized nations (e.g., lung, breast, and colon), should include much greater emphasis on cancer prevention than is presently the case. But there is another perspective. The developing countries, with their dramatic contrasts in lifestyles and environments and equally diverse patterns of cancer, provide an unparalleled, and often neglected, opportunity for studies directed toward understanding the mechanisms of environmental carcinogenesis. Such an understanding should eventually lead to the development of novel intervention approaches. Unfortunately, cancer research is much more difficult to conduct in the developing countries because of the lack of population-based registries, poor communication and transportation systems, and deficiencies in infrastructure, financial support, and the training of health professionals. These difficulties could be overcome, to the benefit of all, if the extent of collaboration in cancer research between the developing and industrialized nations were to be greatly expanded. PMID- 8492317 TI - The lifetime risk of developing breast cancer. AB - BACKGROUND: The lifetime risk of developing breast cancer in U.S. women, often quoted as one in nine, is a commonly cited cancer statistic. However, many estimates have used cancer rates derived from total rather than the cancer-free population and have not properly accounted for multiple cancers in the same individual. PURPOSE: Our purpose was to provide a revised method for calculating estimates of the lifetime risk of developing breast cancer and to aid in interpretation of the estimates. METHODS: A multiple decrement life table was derived by applying age-specific incidence and mortality rates from cross sectional data to a hypothetical cohort of women. Incidence, mortality, and population data from 1975-1988 were used, representing the geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The incidence rates reflected only the first breast primary cancer; mortality rates reflected causes other than breast cancer. The population denominator used in calculating incidence rates was adjusted to reflect only those women without previously diagnosed breast cancers in the hypothetical cohort. RESULTS: Our calculations showed an overall lifetime risk for developing invasive breast cancer of approximately one in eight with use of 1987-1988 SEER data, although up to age 85, it was still the commonly quoted one in nine. CONCLUSION: Our estimate was calculated assuming constant age-specific rates derived from 1987-1988 SEER data. Because incidence and mortality rates change over time, conditional risk estimates over the short term (10 or 20 years) may be more reliable. A large portion of the rise in the lifetime risk of breast cancer estimated using 1975-1977 data (one in 10.6) to an estimate using 1987-1988 data (one in eight) may be attributed to 1) early detection of prevalent cases due to increased use of mammographic screening and 2) lower mortality due to causes other than breast cancer. A common misperception is that the lifetime risk estimate assumes that all women live to a particular age (e.g., 85 or 95). In fact, the calculation assumes that women can die from causes other than breast cancer at any possible age. Cutting off the lifetime risk calculation at age 85 assumes that no women develop breast cancer after that age. While the lifetime risk of developing breast cancer rose over the period 1976-1977 to 1987-1988, the lifetime risk of dying of breast cancer increased from one in 30 to one in 28, reflecting generally flat mortality trends. PMID- 8492316 TI - Folate, methionine, and alcohol intake and risk of colorectal adenoma. AB - BACKGROUND: Reduced methylation of DNA may contribute to loss of the normal controls on proto-oncogene expression. In humans, hypomethylation of DNA has been observed in colorectal cancers and in their adenomatous polyp precursors. Accumulation of DNA methylation abnormalities, observed during progression of human colorectal neoplasia, may be influenced by certain dietary factors. The apparent protective effect of fresh fruits and vegetables, the major folate sources, on colorectal cancer incidence suggests that a methyl-deficient diet contributes to occurrence of this malignancy. Low dietary folate and methionine and high intake of alcohol may reduce levels of S-adenosylmethionine, which is required for DNA methylation. PURPOSE: To determine if dietary factors that may influence methyl availability are related to colorectal adenomas, we prospectively examined the association of folate, methionine, and alcohol intakes and risk of colorectal adenoma. METHODS: We assessed dietary intake for a 1-year period for women of the Nurses' Health Study, started in 1976, and for men of the Health Professionals Follow-up Study, started in 1986--using a semiquantitative food frequency questionnaire. Adenomatous polyps of the left colon or rectum were diagnosed in 564 of 15,984 women who had had an endoscopy between 1980 and 1990 and in 331 of 9490 men who had undergone an endoscopy between 1986 and 1990. RESULTS: High dietary folate was inversely associated with risk of colorectal adenoma in women (multivariate relative risk [RR] = 0.66; 95% confidence interval [CI] = 0.46-0.95 between high and low quintiles of intake) and in men (RR = 0.63; 95% CI = 0.41-0.98) after adjusting for age, family history, indications for endoscopy, history of previous endoscopy, total energy intake, saturated fat intake, dietary fiber, and body mass index. Relative to nondrinkers, drinkers of more than 30 g of alcohol daily (about two drinks) had an elevated risk of adenoma (in women, RR = 1.84, 95% CI = 1.19-2.86; in men, RR = 1.64, 95% CI = 0.92-2.93). Methionine intake was inversely associated with risk of adenomas 1 cm or larger (RR = 0.62; 95% CI = 0.46-0.85, combining men and women). CONCLUSIONS: Folate, alcohol, and methionine could influence methyl group availability, and a methyl-deficient diet may be linked to early stages of colorectal neoplasia. A dietary pattern that increases methyl availability could reduce incidence of colorectal cancer. IMPLICATIONS: These data support efforts to increase dietary folate in segments of the population having diets with low intakes of this nutrient. PMID- 8492318 TI - Relationship of c-myc amplification to progression of breast cancer from in situ to invasive tumor and lymph node metastasis. AB - BACKGROUND: Amplification of the c-myc gene (also known as MYC) occurs in up to 20%-30% of breast cancers and has been associated with poor prognosis. PURPOSE: The purpose of this study was to define the relationship between c-myc amplification and breast cancer progression in order to better understand the biological significance of c-myc amplification. METHODS: We identified invasive tumors with grossly detectable c-myc amplification by using Southern blot analysis to examine frozen tissue from 135 breast carcinomas and polymerase chain reaction (PCR) analysis to examine archival paraffin-embedded tissue from an additional 19 invasive tumors. These 19 tumors were selected on the basis of histologically identifiable in situ and invasive components within the primary tumor and associated lymph node metastases. Amplification of c-myc in these areas was then assessed by quantitative PCR assay. RESULTS: We detected gross c-myc amplification in 10 of the tumors examined--eight of the 135 frozen tissue specimens and two of the 19 archival specimens. We selected five of these 10 invasive tumors for further regional analysis. In all four cases where an in situ component was present, amplification of c-myc was present in both the in situ and the invasive components. However, c-myc amplification was present in the corresponding nodal metastases in only two of the four cases where this could be examined. CONCLUSION: These results suggest that c-myc amplification can occur at an early stage in tumor progression and that amplification does not always persist in the nodal metastasis. PMID- 8492319 TI - Restoration of interferon alpha potentiation of a recombinant ricin A chain immunotoxin following cytoreduction of xenografts of advanced ovarian tumors. AB - BACKGROUND: We have demonstrated that, in the human ovarian carcinoma cell line (OVCAR-3), recombinant human interferon alpha (rHuIFN-alpha) potentiated in vitro inhibition of protein synthesis by immunotoxins. The antitumor activity of intracavitary immunotoxin administered to nude mice 5 days after tumor cell injection was enhanced by a nontherapeutic dose of rHuIFN-alpha, as evidenced by increased survival time. PURPOSE: Our purpose was to determine the outcome of treatment with immunotoxin and rHuIFN-alpha in xenografts of more advanced tumors. METHODS: At 10 or 15 days after tumor cell injection, nude mice with peritoneal OVCAR-3 xenografts were treated intraperitoneally with immunotoxin or with 454A12 monoclonal antibody (MAb) recombinant ricin A chain (rRA), alone or combined with a nontherapeutic dose of rHuIFN-alpha. The immunotoxin was composed of rRA covalently bound to an anti-CD71 (transferrin receptor) MAb. In other experiments, mice were treated intraperitoneally with cyclophosphamide and cisplatin to reduce tumor size on days 20 and 27 after tumor cell inoculation and then, beginning on day 40, with immunotoxin alone or combined with rHuIFN-alpha. RESULTS: Initiation of treatment 10 days after OVCAR-3 transplantation significantly increased median survival from 41 to 89 days (10% survivors on day 120) with 454A12 MAb rRA alone and to more than 120 days (70% survivors) with 454A12 MAb rRA combined with rHuIFN-alpha (P < .0001). The increase in survival time between tumor-bearing mice treated with immunotoxin combined with rHuIFN alpha and those treated with immunotoxin alone was statistically significant (P = .017). In contrast, the 15-day transplant tumors were not curable with immunotoxin therapy (survival, 72 days; 0% survivors) and were refractory to rHuIFN-alpha potentiation (survival, 75 days; 0% survivors). After the second course of chemotherapy to reduce the size of the advanced tumors (day 40), during the ascites cell count nadir, initiation of treatment with 454A12 MAb rRA alone or combined with rHuIFN-alpha resulted in significantly different survival times of 129 and 162 days, respectively (P = .0037). Pathologic examination of surviving mice treated with chemotherapy and 454A12 MAb rRA alone or in combination with rHuIFN-alpha revealed that one (17%) of six mice and 11 (65%) of 17 were tumor free, respectively. CONCLUSIONS: The synergy between immunotoxins and IFN-alpha is dependent on tumor burden. These agents are less effective against large tumor burdens (i.e., advanced stage disease), but their beneficial effects re-emerge after cytoreduction by combination chemotherapy. IMPLICATIONS: The ideal setting for testing the efficacy of intracavitary immunotoxin combined with rHuIFN-alpha after front-line chemotherapy is in patients with residual tumor refractory to additional chemotherapy or in those with toxic effects that prevent delivery of effective doses. PMID- 8492320 TI - Reduced risk of large-bowel adenomas among aspirin users. The Polyp Prevention Study Group. AB - BACKGROUND: Epidemiological studies have indicated that aspirin consumption can lower the risk of large-bowel cancer. These studies are not entirely consistent, however, and their interpretation has been complicated by the possibility that cancer symptoms may have led patients to avoid aspirin or that aspirin may have influenced cancer diagnosis and treatment. PURPOSE: Our purpose was to determine the effect of aspirin on risk of large-bowel neoplasms in a study in which aspirin use would not be expected to affect tumor detection and tumor-related symptoms would not likely influence aspirin use. A less complicated assessment of the relationship between aspirin and large-bowel tumors should thus be possible. METHODS: We studied 793 patients enrolled in a clinical trial of nutrient supplements to prevent large-bowel adenomas. Unlike invasive cancers, adenomas usually do not cause symptoms or detectable gastrointestinal bleeding; thus, adenomas are unlikely to influence aspirin use. Each patient had at least one large-bowel adenoma diagnosed and removed shortly before study entry and had been judged to be free of further tumors by colonoscopy. Use of aspirin was assessed by responses on questionnaires administered 6 and 12 months after enrollment. We performed complete colonoscopies on all patients 1 year after they entered the study and removed all polyps. RESULTS: Patients who reported taking aspirin on both questionnaires (consistent users) had a lower risk of new adenomas at their 1-year follow-up colonoscopy (odds ratio = 0.52; 95% confidence interval = 0.31 0.89) compared with patients who did not report using aspirin on either of the questionnaires. The apparent protective effect of consistent aspirin use was present among both men and women and did not appear to be influenced by the number of prior adenomas. CONCLUSIONS: These data further support the hypothesis that aspirin has an antineoplastic effect in the large bowel. Nevertheless, the question of whether aspirin should be used to prevent large-bowel tumors would be best answered by a randomized controlled clinical trial specifically designed to address this issue. PMID- 8492321 TI - Acute myelogenous leukemia. PMID- 8492322 TI - Anti-inflammatory drugs and rheumatoid arthritis. PMID- 8492323 TI - Regulation of pesticides in Cameroon. AB - To fight against pests and vectors of certain diseases, Cameroon imports and makes use of pesticides. Importation and utilization are subject to regulation from importers to users. The goal of this study is to evaluate the actual regulatory system of pesticides in Cameroon. From this study has emerged the fact that Cameroon has insufficient legislation for pesticides. Registration does not exist, and the ministry of agriculture restricts itself to issuing attestation of importation, if the product is effective, to those who write an application. Importation and distribution are done in conditions that are far from ideal. To remedy this inadequacy, it is necessary to train and inform all those intervening in this domain and put in place research infrastructures. Appropriate legislation elaborated in a broad consultation with competent authorities in pesticides is also needed. PMID- 8492324 TI - Modulation of liver intracellular C3 in mice by 2,3,7,8-tetrachlorodibenzo-p dioxin. AB - Earlier studies from this laboratory have shown that the complement system, especially the component C3, in female B6C3F1 mice is suppressed following TCDD exposure in vivo. However, the direct exposure of TCDD in vitro does not affect the C3-producing capacity of two types of hepatoma cells, as well as mouse primary hepatocytes. To investigate the effect of TCDD on C3 production by the liver following in vivo exposure, liver intracellular C3 levels and pro-C3, the precursor of the secreted C3, were examined in the present study. The results demonstrated that there was a dose-dependent increase of liver intracellular C3 levels (from 138% to 175% of control) immediately following TCDD (from 10 to 40 micrograms/kg) exposure. This increase was rapid (4 h after exposure), but transient (less than 2 h), and was not accompanied by an alteration of serum C3 levels. Studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the increase in liver intracellular C3 levels resulted from, at least partially, an increase in intracellular pro-C3. Serum C3 levels did not decrease until d 3 after exposure, when both liver intracellular C3 levels and pro-C3 in TCDD-treated mice were not different from those of the control mice. These results indicated that the modulation of liver intracellular C3 by TCDD did not correlate with the suppression of serum C3 levels following exposure. PMID- 8492325 TI - A multiyear study of blood cholinesterase activity in urban pesticide applicators. AB - This article is a review of blood cholinesterase activity in a cohort of urban pesticide applicators ranging from 1680 to over 3800 workers. During the period 1981-1991, 208, 788 blood samples were taken for measurement of cholinesterase activity with an average of 6 samples per year from each worker. A total of 150 workers or 0.44% of the cohort was removed from exposure to cholinesterase inhibiting insecticides because of decreased cholinesterase activity. No worker required treatment for signs of cholinesterase inhibition. PMID- 8492326 TI - Aquatic biomonitoring of reclaimed water for potable use: the San Diego Health Effects Study. AB - Highly treated reclaimed wastewater was evaluated as a possible supplement to raw water sources required to meet San Diego's growing need for potable water. Biomonitoring experiments employing fathead minnows (Pimephales promelas) were used to compare reclaimed water with the city's current raw water supply. Juvenile fish were exposed in flow-through aquaria in field laboratories located at the reclamation plant (AQUA II) and at a municipal potable water treatment facility (Miramar). Biomonitoring measurements were survival and growth, swimming performance, and trace amounts of 68 base/neutral/acid extractable organics, 27 pesticides, and 27 inorganic chemicals found in fish tissues after exposure. Biomonitoring revealed differences in survival, growth, and swimming performance only after 90- and 180-d exposure. Reclaimed water and raw water were not readily distinguishable in 28-d chemical bioaccumulation tests in terms of organic chemical contaminants in fish tissue except for pesticide levels, which tended to be higher in raw water. Similar inorganic species were found in samples from both waters, although there was greater evidence of bioaccumulation of certain contaminants from raw water. Based on biomonitoring parameters included in these experiments, the use of reclaimed water to supplement raw water supplies would appear to pose no major public health threats. The results of these studies will be combined with additional health effects information before final conclusions are reached about the suitability of reclaimed water for human consumption. PMID- 8492327 TI - Prediction of carcinogenicity from two versus four sex-species groups in the carcinogenic potency database. AB - Prediction of a positive result in rodent carcinogenesis bioassays using two instead of four sex-species groups is examined for the subset of chemicals in the Carcinogenic Potency Database that have been tested in four sex-species groups and are positive in at least one (n = 212). Under the conditions of these bioassays, a very high proportion of rodent carcinogens that are identified as positive by tests in four groups is also identified by results from one sex of each species (86-92%). Additionally, chemicals that are classified as "two species carcinogens" or "multiple-site carcinogens" on the basis of results from four sex-species groups are also identified as two-species or multiple-site carcinogens on the basis of two sex-species groups. Carcinogenic potency (TD50) values for the most potent target site are similar when based on results from two compared to four sex-species groups. Eighty-five percent of the potency values are within a factor of 2 of those obtained from tests in 4 sex-species groups, 94% are within a factor of 4, and 98% are within a factor of 10. This result is expected because carcinogenic potency values are constrained to a narrow range about the maximum dose tested in a bioassay, and the maximum doses administered to rats and mice are highly correlated and similar in dose level. Information that can be known in advance of a 2-yr bioassay (mutagenicity, class, route, and maximum dose to test) does not identify groups of rodent carcinogens for which four sex-species groups are required to identify carcinogenicity. The range of accurate prediction of carcinogenicity using only male rats and female mice is 93% among mutagens and 88% among nonmutagens; for various routes of administration, 88-100%; for various chemical classes, 75-100%; and for various levels of the maximum dose tested, 81-100%. Results are similar for the pair male rats and male mice. Using a strength of evidence approach, weaker carcinogens are somewhat less likely than stronger carcinogens to be identified by two sex species groups. Strength of evidence is measured using the proportion of experiments on a chemical that are positive, the extent to which tumors occur in animals that die before terminal sacrifice, and whether the chemical induces tumors at more than one site and in more than one species. PMID- 8492328 TI - Mouse Hepa 1c1c7 hepatoma cells produce complement component C3; 2,3,7,8 tetrachlorodibenzo-p-dioxin fails to modulate this capacity. AB - Previous studies from this laboratory have shown that 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD) decreased complement component C3 levels in female B6C3F1 mouse serum following in vivo acute or subchronic exposure (White et al., 1986). Since TCDD is a hepatotoxic compound and more than 90% of serum C3 is produced by the liver, studies were undertaken using mouse Hepa 1c1c7 (Hepa 1) hepatoma cell line to determine if TCDD acts directly on hepatocytes to inhibit C3 production. The C3-producing capacity of Hepa 1 cells was first examined. When confluent Hepa 1 cell monolayers were cultured in 24-well plates with serum-free medium, a detectable amount of C3 (14.1 +/- 0.8 ng/ml) was secreted as early as 1 h after culture and reached a plateau at 12 h (68.3 +/- 4.9 ng/ml). Furthermore, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that the molecular weight of C3 in culture supernatant corresponded to that present in mouse serum. Human recombinant IL-1 beta (hrIL-1 beta), a known inducer of complement C3, at doses as low as 1 unit/ml increased the C3 production to 158% of control after 24 h of incubation. The effect of hrIL-1 beta was dose dependent, and the maximum tested dose of 10 units/ml increased C3 production to 256% of control. When cells were directly exposed to TCDD at concentrations from 10(-10) to 10(-6) M, there was no inhibitory effect on production of C3. TCDD also failed to block the stimulatory effect of 10 units/ml hrIL-1 beta added to the culture 1 h later. To verify that cultured Hepa 1 cells were able to respond to TCDD, 7-ethoxyresorufin O-deethylase (EROD) activity was measured under the same conditions. TCDD dose-dependently increased EROD activity of Hepa 1 cells at 24 h following exposure. The activity reached 56.7 +/- 3.0 pmol/min/mg protein with 10(-9) M TCDD, compared with 10.7 +/- 1.7 pmol/min/mg protein of vehicle-exposed cells. Our results indicate that the direct interaction of TCDD with Hepa 1 cells does not affect their C3-producing capacity, although EROD activity, a characteristic response mediated by the cellular TCDD/Ah receptor, was induced. The lack of effect of TCDD in vitro suggests that the decrease of serum C3 levels observed in vivo may result from an indirect effect of TCDD on hepatocytes. PMID- 8492329 TI - No enhancing effects of calcium/magnesium salts of L-glutamate and L-ascorbate on tumor development in a rat medium-term multiorgan carcinogenesis bioassay. AB - Calcium/magnesium salts of L-glutamate and L-ascorbate were tested for modification potential using a rat multiorgan carcinogenesis bioassay. Following sequential treatment with three different carcinogens (diethylnitrosamine, N methylnitrosourea, and dihydroxydi-N-propylnitrosamine) over a 4-wk period, rats were given diet containing 5% monocalcium di-L-glutamate tetrahydrate (Ca glutamate), 2.5% monomagnesium di-L-glutamate tetrahydrate (Mg-glutamate), 5% L glutamic acid, 5% monocalcium di-L-ascorbate dihydrate (Ca-ascorbate), 2.5% monomagnesium di-L-ascorbate dihydrate (Mg-ascorbate), or 5% L-ascorbic acid for 16 wk. Body weight increase was slightly suppressed in the groups receiving Ca ascorbate, Mg-ascorbate, and ascorbic acid supplementation after the carcinogen treatments. While administration of Ca-glutamate or Ca-ascorbate raised urinary pH, ascorbic acid values were decreased. Concentrations of calcium and magnesium ions in the urine increased after ingestion of Ca-glutamate or Ca-ascorbate, and Mg-glutamate or Mg-ascorbate, respectively, but phosphorus levels decreased in all groups given calcium and magnesium salts. No consistent treatment-related changes in the concentrations of sodium or potassium ions in the urine were detected. Histopathological investigation at wk 20 did not demonstrate any modification of tumorigenesis with regard to the incidence of frequency of lesions developing in the various target organs/tissues. The present results thus revealed no apparent enhancement of carcinogenesis at any site, including the urinary system, by calcium or magnesium salts using the present rat multiorgan carcinogenesis bioassay. PMID- 8492330 TI - Relationship between bisacodyl-induced urolithiasis and rat urinary bladder tumorigenesis. AB - Dietary supplementation with bisacodyl at concentrations ranging from 1 to 0.3% was found to induce both calculi and epithelial proliferative lesions, including a transitional-cell carcinoma, in the urinary bladder of F344/DuCrj rats. In order to clarify the relationship between the bisacodyl-associated urinary bladder calculi and the development of proliferative lesions in the urinary bladder, male and female rats were administered bisacodyl-diets at concentrations of 0.3, 0.1, and 0.03% for 32 wk. Both sexes of animals treated with bisacodyl suffered from diarrhea throughout the experimental period. Epithelial proliferative lesions and calculus formation were observed only in the urinary bladder of male rats given the 0.3% bisacodyl diet. Proliferative lesions and increases of bromouracil deoxyriboside (BUdR) labeling indices were found only in the urinary bladder epithelium of rats with calculi, the severity of the former correlating with the calculus weight and being most marked in the dome areas, which are susceptible to physical stimulation. These findings indicate a close relationship between the development of proliferative lesions and the existence of calculi in the urinary bladder, and suggest that bisacodyl-induced proliferative lesions are not caused directly by bisacodyl per se but are secondary to calculus formation. PMID- 8492331 TI - Comparison of lead bioavailability in F344 rats fed lead acetate, lead oxide, lead sulfide, or lead ore concentrate from Skagway, Alaska. AB - An animal model using rats was developed to initiate investigations on the bioavailability of different sources of environmental lead. Lead must be absorbed and transported to target organs like brain, liver, kidney, and bone, before susceptible cells can be harmed. The bioavailability and therefore the toxicity of lead are dependent upon the route of exposure, dose, chemical structure, solubility, particle size, matrix incorporation, and other physiological and physicochemical factors. In the present study male F344 rats were fed < or = 38 microns size particles of lead sulfide, lead oxide, lead acetate, and a lead ore concentrate from Skagway, Alaska, mixed into the diet at doses of 0, 10, 30, and 100 ppm as lead for 30 d. No mortality or overt symptoms of lead toxicity were observed during the course of the study. Maximum blood lead concentrations attained in the 100 ppm groups were approximately 80 micrograms/dl in rats fed lead acetate and lead oxide, and were approximately 10 micrograms/dl in those fed lead sulfide and lead ore concentrate. Maximum bone lead levels in rats fed soluble lead oxide and lead acetate were much higher (approximately 200 micrograms/g) than those seen in rats fed the less soluble lead sulfide and lead ore (approximately 10 micrograms); kidney lead concentrations were also about 10 fold greater in rats fed the more soluble compared to the less soluble lead compounds. However, strong correlations between dose and tissue lead concentrations were observed in rats fed each of the four different lead compounds. Kidney lesions graded as minimal occurred in 7/10 rats fed 30 ppm and in 10/10 rats fed 100 ppm lead acetate, but not at lower doses or from other lead compounds. Similarly, urinary aminolevulinic acid excretion, a biomarker for lead toxicity, was increased in rats fed 100 ppm lead acetate or lead oxide, but was unaffected at lower doses or by the less soluble lead compounds. Although the histological and biochemical responses to lead toxicity were restricted to the more soluble lead compounds in this study, lead from Skagway lead ore concentrate and lead sulfide was also bioavailable, and accumulated in proportion to dose in vulnerable target organs such as bone and kidney. Longer-term studies with different mining materials are being conducted to determine if tissue lead continues to increase, and whether the levels attained are toxic. Data from such studies can be used to compare the toxicity and bioavailability of lead from different sources in the environment. PMID- 8492332 TI - Fishing in contaminated waters: knowledge and risk perception of hazards by fishermen in New York City. AB - Risk perception studies show that people may underestimate significant risks while overestimating others. Further, government agencies may assume the public becomes aware of risks when the agency has issued advisories, when in reality a segment of the population remains unaware of these warnings. This article reports on a survey of people fishing on the catchment basins of Jamaica Bay Wildlife Refuge in New York City. Of the 154 groups interviewed, only 19% believed the waters or fish were contaminated or unsafe, despite state warnings to the contrary. Fishermen made nearly five visits per month, and ate an average of three fish a week, (remaining fish were eaten by their families) and fish were usually fried. Most people believed the fish were safe to eat, or that they could recognize if one was spoiled. Thus, most people were ignoring the health advisories on consuming fish from these waters. We suggest that these fishermen are unaware of health advisories, or ignore them because the fishing situation is familiar, voluntary, pleasurable, and has not resulted in their illness. Since they believe they can determine if the fish are bad from smell and appearance, they have changed their own analysis from the unknown (chronic, delayed risks from toxics) to the known (immediate illness), lowering their perceived risk, but not the actual risk. PMID- 8492333 TI - Facility assessment guidelines for regional toxicology treatment centers. American Academy of Clinical Toxicology. PMID- 8492334 TI - What's in a name?--Regional Toxicology Treatment Centers. PMID- 8492335 TI - Regional poison systems--roles and titles. PMID- 8492336 TI - Clinical toxicology in the 1990s: the development of clinical toxicology centers- a personal view. PMID- 8492337 TI - Kinetics of toxic doses of paraquat and the effects of hemoperfusion in the dog. AB - Knowledge of the kinetics of an intoxicant is required for designing potential therapies in poisoned patients. In the case of paraquat, elucidating the kinetics has been made difficult by the paraquat-induced renal failure and the consequent dose- and time-dependent elimination of the herbicide. In the current study, we have modelled the plasma and urinary concentrations of paraquat in dogs given a toxic dose, the elimination of which was nonlinear. This enabled us, in turn, to simulate the apparent concentrations of paraquat in the deep tissue compartment, part of which is constituted by the major target organ for paraquat toxicity, the lung. Finally, we defined conditions, if any, under which charcoal hemoperfusion could reduce exposure of the deep compartment to paraquat by > or = 25%. We found that the plasma concentrations of paraquat could be described by a two compartment model with non-linear elimination from the central compartment. Use of a three compartment model did not improve the fit over that for a two compartment. The volume of distribution of paraquat at steady state approximated that of total body water. Simulated hemoperfusion performed for eight or eighty hours did not reduce exposure of the deep compartment to paraquat by > or = 25%, unless begun at times < or = two hours of the infusion commencing. This is consistent with our experimental data in the dog. The lack of efficacy of hemoperfusion is due to the rapid renal elimination of most of the absorbed dose of paraquat over the first 12 hours after its administration, and the later limitation of the rate of removal of paraquat from the body by the slow efflux rate from the deep to central compartment. PMID- 8492338 TI - Clinical features and management of digitalis poisoning--rationale for immunotherapy. AB - The intensity of gastrointestinal and visual symptoms together with hyperkalemia and the characteristic ECG features make diagnosis of acute digitalis intoxication relatively easy. Death results mainly from ventricular fibrillation or from ventricular asystole or pump failure. Mesenteric infarct may also occur in elderly patients. Previous assessment of outcome has shown that mortality increases in patients exhibiting five prognostic factors: 1) advanced age; 2) heart disease; 3) male sex; 4) high-degree atrioventricular block; 5) hyperkalemia. Conventional treatment includes gastric lavage, activated charcoal and supportive care. First-line antiarrhythmic therapy is usually atropine, because of bradycardia-induced arrhythmia. Ventricular pacing is a toxicodynamic treatment that may be helpful in both bradycardia-induced arrhythmia and high degree atrioventricular block. Pacing is difficult to handle and can result in serious adverse effects. Immunotherapy has two advantages. First, a strong toxicodynamic effect due to quick reversal of digitalis-induced dysrhythmias, hyperkalemia, and myocardial depression, by reactivation of membrane ATPases. Second, a toxicokinetic effect due to accelerated renal excretion of Fab digitalis complexes. Since this therapy is well tolerated and efficient, we recommend early administration of Fab fragments as soon as poor prognostic factors are identified. PMID- 8492339 TI - Acute digitalis intoxication--is pacing still appropriate? AB - Over a six year period, 92 patients intoxicated with either digitoxin or digoxin were admitted to our ICU. Fifty-one patients were treated with cardiac pacing and/or Fab fragments, and the mortality rate was 13% (14 were intoxications with digoxin, 36 with digitoxin, 1 was mixed). Forty-five cases were suicide attempts; six were accidental overdosages. Since cardiac pacing may trigger fatal arrhythmia or delay the administration of Fab fragments, we conducted a retrospective study to determine whether fatal outcomes could be related either to cardiac pacing or to unsatisfactory use of immunotherapy. In our study, prevention of life-threatening arrhythmia failed in 8% of cases with Fab and in 23% with pacing. Though Fab tended to be more effective, this difference was not significant. In our study, the main obstacles to the success of Fab were pacing induced arrhythmias and delayed or insufficient administration of Fab. Iatrogenic accidents of cardiac pacing were frequent (14/39, 36%) and often fatal (5/39, 13%). In contrast, immunotherapy was not associated with any serious adverse effects (0/28, 0%) and was safer than cardiac pacing (p < 0.05). In conclusion, during digitalis intoxication, the pacemaker has limited preventive and curative effects, is difficult to handle, and exposes patients to severe iatrogenic accidents. Fab fragments act as a powerful antidote and are safer and much easier to use than pacing. These results encourage us to prescribe Fab fragments as first-line therapy during acute digitalis intoxication. PMID- 8492340 TI - Revising the management of digitalis poisoning. PMID- 8492341 TI - Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. AB - The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers. PMID- 8492342 TI - The price of gold: mercury exposure in the Amazonian rain forest. AB - Concern has surfaced over the recent discovery of human mercury exposure throughout the tropical rain forest of South America's Amazon River Basin. The probable source of mercury has been traced to gold mines located within the interior. The mining process involves the extraction of gold from ore by burning off a mercury additive, resulting in vaporization of elemental mercury into the surrounding environment. The purpose of this case series is to document mercury levels in miners and local villagers presenting with a history of exposure, or signs and symptoms consistent with mercury toxicity. Over a five year period (1986-91), the whole blood and urine mercury levels of 55 Brazilian patients demonstrating signs and symptoms consistent with mercury exposure were collected. Thirty-three (60%) of the subjects had direct occupational exposure to mercury via gold mining and refining. Whole blood mercury levels ranged from 0.4-13.0 micrograms/dL (mean 3.05 micrograms/dL). Spot urine levels ranged 0-151 micrograms/L (mean = 32.7 micrograms/L). Occupational mercury exposure is occurring in the Amazon River Basin. Interventions aimed at altering the gold mining process while protecting the workers and surrounding villagers from the source of exposure are essential. The impact of the gold mining industry on general environmental contamination has not been investigated. PMID- 8492343 TI - A five year evaluation of acute exposures to phenol disinfectant (26%). AB - A five year retrospective review of all exposures to a high concentration phenol disinfectant (Creolin Disinfectant 26% phenol) reported to a regional poison center located 96 cases, with 16 cases lost to follow up. There were 60 oral-only exposures, 7 dermal-only exposures and 12 oral/dermal exposure. One patient was an inhalation exposure. Fifty-two cases (65%) were evaluated in a hospital. Eleven patients with oral exposures (14%) experienced rapid CNS depression, but no seizures occurred. Vomiting, coughing, and stridor was noted in 14, 7 and 4 patients respectively. Burns were noted in 17 of 72 (24%) patients with oral exposure and 5 of 19 (26%) with dermal exposure. Seventeen patients underwent endoscopy. Tissue sloughing was noted in one case. All other burns were first degree. No cardiovascular complications occurred. Twenty-eight patients (35%) were followed at home via telephone with one episode of vomiting and one episode of dermal irritation occurring. CNS toxicity from exposure to a high concentration phenol containing cleaning product appears to be rapid in onset. The absence of serious toxicity and major chemical burns in this series does not eliminate concern with the corrosive and systemic risks of phenol poisoning. PMID- 8492344 TI - Pharmacokinetics of obidoxime in organophosphate poisoning associated with renal failure. AB - Obidoxime is an oxime used in several countries as an antidote in organophosphate intoxication. Its pharmacokinetics were studied in a 20 year-old female with severe and complicated methamidophos intoxication. Obidoxime elimination half life was 6.9 h, volume of distribution 0.845 L/kg, total body clearance 85.4 mL/min, and renal clearance 69 mL/min (creatinine clearance 54 mL/min). Eighty percent of the dose was excreted in the urine over 5 h. Possible reasons for the different pharmacokinetic values as compared with values previously reported in healthy volunteers are discussed. Obidoxime dose should be adjusted according to renal function. More studies are needed to establish the therapeutic window of obidoxime in patients with organophosphate intoxication. PMID- 8492345 TI - Atrazine in plasma and tissue following atrazine-aminotriazole-ethylene glycol formaldehyde poisoning. AB - A high performance liquid chromatography method has been used to study the plasma kinetics of atrazine in a human fatality after ingestion of a herbicide mix containing atrazine, aminotriazole, ethylene glycol and formaldehyde. A hemodialysis was performed in an effort to eliminate these toxic substances. The mean atrazine clearance over 4 h was 250 mL/min and the dialysance of atrazine was calculated as 76%. On autopsy, the kidney showed the highest concentration of atrazine (97.62 micrograms/g-1 wet tissue) with lesser concentrations in the lung, small intestine and liver, and the lowest concentration in the heart. PMID- 8492346 TI - Loxoprofen--another NSAID associated with acute asthmatic death. AB - Loxoprofen sodium (sodium 2[4-(2-oxocyclopentylmethyl) phenyl] dehydrate; CAS #68767-14-6) is a nonsteroidal, inflammatory drug marketed only in Japan. A case report describes its association with an acute asthmatic death with features resembling those evoked by similar drugs. The analytic methodology is reported. The blood levels of loxoprofen were in the therapeutic range. The tissue concentrations are reported. PMID- 8492347 TI - Tetany and rhabdomyolysis due to surreptitious furosemide--importance of magnesium supplementation. AB - Diuretics may induce hypokalemia, hypocalcemia and hypomagnesemia. While severe hypokalemia may cause muscle weakness, severe hypomagnesemia is associated with muscle spasms and tetany which cannot be corrected by potassium and calcium supplementation alone (1,2). Surreptitious diuretic ingestion has been described, mainly in women who are concerned that they are obese or edematous. Symptomatic hypokalemia has been reported in such patients (3-7) and in one case hypocalcemia was observed (8), but the effects of magnesium depletion were not noted in these patients. PMID- 8492348 TI - A fatal case of acute boric acid poisoning. AB - A 77 year-old male mistakenly ingested an estimated 30 g of boric acid as a single oral dose to stop hiccups. On admission, he had vomiting, diarrhea, and hiccups. Laboratory data was diagnostic of acute renal failure. Hemodialysis and charcoal hemoperfusion were performed in series. The serum concentration of boric acid was reduced by the therapy, but the patient died due to cardiac insufficiency. Acute boric acid poisoning resulting from a single oral dose in adults has rarely been reported. Our case is the fourth fatal case in adults since the 1920s following a single, acute ingestion of boric acid. PMID- 8492349 TI - Kinetics of trichloroethylene elimination from venous blood after acute inhalation poisoning. AB - The kinetics of trichloroethylene were examined in three men, 28-36 years old, hospitalized after an acute occupational exposure. The trichloroethylene concentration of venous blood was determined by gas chromatography with headspace analysis; urinary trichloroacetic acid was assayed by the colorimetric method of Fujiwara. The kinetics of blood trichlorethylene (t1/2 21.7 h) and the urinary elimination of trichloracetic acid over six days were used to calculate the total inhalation exposures. Blood trichlorethylene was diagnostically more relevant than urinary trichloracetic acid. PMID- 8492350 TI - Bismuth poisoning and chelation. PMID- 8492351 TI - [Diagnostic delay and related factors in women with breast cancer]. AB - This was a retrospective descriptive study examining responses to the discovery of breast symptoms and the determinants of delay in diagnosis of women with breast cancer. There were 71 women recruited from a medical center Out-Patient Department (OPD) and asked to complete structured questionnaires. On completion of the questionnaires face-to-face interviews were conducted in private. The validity and reliability of the instruments were measured and the correlation coefficients were found to be acceptable (0.64-0.84). Ninety-six percent of the women had self-discovered breast symptoms that included breast lumps, sensation of pain, nipple retraction and nipple secretion. Responses to the discovery were categorized as "worry or fear", "have no unusual sensation", "suspicion", "wait and see", "feel sorry" and "prayer". The time delay between discovery of breast cancer symptoms and pathological diagnosis ranged from less than one week to over six months. Stepwise multiple regressions were computed. The socioeconomic status, education, and Powerful Others Health Locus of Control (PHLC) were the most powerful predictors; together they explained 46% of the variance for diagnostic delay. Also, we found diagnostic delay was significantly correlated with the clinical stage when Sperman's correlation was tested (r = 0.73, P < 0.01). It was indicated that subjects with delayed diagnosis showed a possibility of poorer prognosis at the clinical stage. Nursing implications and strategies are discussed. PMID- 8492352 TI - Open heart surgery in a patient with an implanted pacemaker: case report. AB - When a patient has a pacemaker and requires operation, surgeons have to consider some possible intraoperative pacemaker complications induced by electrocautery. Electrocautery is commonly used during surgery to achieve hemostasis. However, this very effective tool may introduce innumerable problems in the paced patient, including irreversible damage to the pulse generator, pacemaker reprogramming, induction of a rise in the capture threshold, and ventricular fibrillation. Although electrocautery may be avoided in some surgical procedures, open heart surgery cannot be performed without it. One case is presented to illustrate how to achieve hemostasis while decreasing electric interference and how to protect the permanent pacemaker while avoiding those possible complications during the defibrillation. The purpose of this article is to call attention to potential problems induced by electrocautery and in an effect to facilitate the perioperative management of the paced patient undergoing open heart surgery. PMID- 8492353 TI - Tracheal deviation: an unusual complication of platysma myocutaneous flap. AB - Reconstruction of the intraoral defect caused by tongue cancer was done for a patient by using a platysma myocutaneous flap. The relatively short neck, scar contracture, and inactive movement of the involved side of the neck resulted in tracheal deviation, an unusual complication not appearing in previous reports. In order to avoid airway problems during intubation, the surgeon and anesthestist should seriously consider the possibility of this rare complication in patients who have had the platysma myocutaneous flap technique. Careful preoperative evaluation and skillful intubation of the fiberoptic bronchoscope are demanded in cases where next general anesthesia is needed. PMID- 8492354 TI - Evaluation of prognostic indices based on pulmonary and hemodynamic variables in patients with adult respiratory distress syndrome (ARDS). AB - Patients with established ARDS have a high mortality rate. We continuously monitored hemodynamic and respiratory parameters of 30 patients in our ICU, all had acute respiratory failure during admission then progressively developed ARDS. We compared demographic characteristics, APACHE II (acute physiology and chronic health evaluation) score, ALI (acute lung injury) score, associated MSOF (multiple systems organ failure) in the disease process, pulmonary variables, and hemodynamic variables between survivors and nonsurvivors. Six of the 12 female patients and two of the 18 male patients survived. Our female patients had a better outcome than the males (P < 0.02); and, those who were younger than 35 years old and those who had less than two organ failures during the evolution of ARDS also had a better outcome (P < 0.001 vs. P < 0.03). After ARDS had developed, there were significant differences between survivors and nonsurvivors in the APACHE II score (P < 0.03), serum albumin level (P < 0.02), mean airway pressure (P < 0.05), PCWP (P < 0.02) and SaO2 (P < 0.02). Having a higher APACHE (> or = 15, P < 0.003), lower serum ablumin level (Alb < 2.5 gm/dl, P < 0.04), higher mean airway pressure (> or = 25 cm H2O, P < 0.04), higher PCWP (> or = 14 mmHg, P < 0.006), and lower SaO2 (< 93%, P < 0.002) predicted a poorer outcome. All patients received PEEP therapy and there were no significant differences between survivors and nonsurvivors in the PEEP level applied, either at the beginning of respiratory failure, or after development of ARDS. But those who had PEEP of 6 cm H2O or higher applied at the beginning of respiratory failure and those had PEEP of less than 10 cm H2O after development of ARDS had a better outcome (P < 0.04 vs. P < 0.05). Nevertheless, more controlled trials are needed before we make any conclusion about PEEP therapy. PMID- 8492355 TI - Asbestos related pleural plaques in retired boiler room workers. AB - Occupational disease is often underestimated and only a few formal reports have been published in Taiwan. This study reports of a group of workers with asbestos induced-disease, pleural plaque in Taiwan. Pleural plaque is a marker of exposure to asbestos. The disease was found in chest radiographs of five boiler room workers in a sugar refining factory. The chest radiographs of 248 current workers in that plant were reviewed, and none of them was found to have pleural plaques. The storage of asbestos and the long-time use of mixed asbestos cement for insulation of the inner wall of the stove and pipes were found in the factory. The authors believe that the pleural plaques might be resulted from occupational exposure to asbestos. It is suggested that the use of asbestos should be prohibited, step by step, and regular follow-up of the workers with an asbestos exposure history is required. PMID- 8492356 TI - [Kinetic studies of protein kinase A in rat liver during early sepsis]. AB - Sepsis-induced glucose dyshomeostasis has been characterized by an initial hyperglycemia followed by a progressive hypoglycemia. It is well known that the liver plays a predominant role on regulating the homeostatic level of blood glucose. Furthermore, recent studies indicate that protein kinase A, activated by c-AMP, contributes to the role of glycagon in glucogenolysis and glyconeogenesis. Kinetic studies of protein kinase were completed. During late sepsis, in order to further understand the pathophysiology of hepatic glucose disturbances during sepsis. This study investigates the role of protein kinase A in the liver regulating carbohydrate metabolism during early sepsis. The work was performed by using an animal septic model, induced by cecal ligation and puncture (CLP) operation. Through the measurement of blood sugar, a two phase change in sugar level was found. That is, blood sugar significantly increased at 4.5 hrs after CLP operation (p < 0.05) and then significantly decreased at 18 hrs (p < 0.01). In the kinetic studies of protein kinase A, the results showed that, during early sepsis, the activities of both type I (eluted at low ionic strength) and type II (eluted at high ionic strength) protein kinase A were unchanged. Moreover, the kinetic parameters, Vmax and S0.5, of protein kinase A showed no significant difference between two groups. As such, it is suggested that hyperglycemia during early sepsis is not connected to the regulation of protein kinase A. PMID- 8492357 TI - [Muscle blood flow in lower limbs of healthy Chinese and variance according to sex and age]. AB - The Xe-133 clearance method is used to measure muscle blood flow in the lower limbs to establish normal values and evaluate the variance between different sex and age groups in healthy Chinese. 99 healthy volunteers were included in this study and divided into three groups according to age and two groups according to sex. Group I: < 40 y/o, 34 persons; Group II: 41-60 y/o, 30 persons; Group III: > 60 y/o, 35 persons; male group: 51 persons; and female group: 48 persons. Intramuscular injection of Xe-133 saline solution in the anterior tibial muscle of the right leg was performed in all the volunteers to calculate muscle blood flow. The muscle blood flow is 3.21 +/- 1.29 ml/100 gm/min in Group I, 3.19 +/- 1.28 in Group II, 2.71 +/- 1.17 in Group III, 3.09 +/- 1.38 in male, and 2.96 +/- 1.24 in female. There was no significant difference in Groups I and II, or in the male and female groups using the Student's t test for unpaired data. However, a mild difference was observed between Groups I and III, and between Groups II and III (P values of 0.09 and 0.11 respectively). We conclude that there is no variance of muscle blood flow in the lower limbs between different sexes and the effect of aging on peripheral muscle blood flow is not significant before 60 in healthy Chinese. PMID- 8492358 TI - [Strategics of medical centers and regional hospitals in response to new labour insurance fee schedule]. AB - The purpose of this paper is to evaluate the medical centers and regional hospitals, strategic response to the implementation of new labour insurance fee schedule. This survey selects fifty-one medical centers and regional hospitals, with the response rate of 92.73%. This questionnaire was developed and evaluated by the authors and mailed to the questionnaire response by hospital's director or relative department director. We have selected Shortell et al. (1985) theory as the framework for evaluating and explaining hospital response to regulation environment (ex: change in the reimbursement system) at institutional-level response (ex: hospital association activity aimed at influencing regulation), managerial-level response (ex: increased physician participation in hospital-wide decision making; starting or expanding a planning department) and technical-level response (ex: shared clinical services such as lab., X-ray, pharmacy). The result found that hospitals with the characteristics as non-public ownership, medical centers, bigger size, and more administrative staff are more inclined to adopt institutional-level response. And a technical-level response occurs to hospital when market competibility becomes more intense which leads to higher reimbursement resource dependency. PMID- 8492359 TI - Thyroid function in children with beta-thalassemia major in north Jordan. AB - Basal thyroid function was assessed by serum thyroxine, tri-iodothyronine and thyroid-stimulating hormone levels in 90 patients 2-10 years old with beta thalassaemia major. Based on measured serum ferritin levels, patients were classified into two groups: group (I) which included 63 patients with ferritin concentrations ranging from 300 to 7000 ng/ml (mild iron overload) and group (II) which included 27 patients with ferritin concentrations higher than 7000 ng/ml (severe iron overload). The results of thyroid function in both groups were compared with those of 50 control subjects. In group (I), the mean concentrations of all measured hormones were not significantly different from those of the controls. In group (II), the mean concentrations of thyroxine and tri iodothyronine decreased by 29 and 35 per cent (P < 0.05), respectively, and the mean concentration of thyroid-stimulating hormone showed a 2.6-fold increase (P < 0.01) in comparison with those of the controls. The data clearly demonstrate the occurrence of impaired thyroid function and its possible association with iron overload in a considerable proportion of transfusion-dependent beta-thalassaemic patients. PMID- 8492360 TI - Identification of factors associated with the growth of schoolchildren in southern Iran. AB - The effects of socio-economic/cultural factors on the growth of school children in the city of Shiraz (Southern Iran) are examined by using univariate and multivariate analysis (ANOVA and MANOVA). Districts of residence and fathers' level of education are identified as the factors affecting the growth of children after adjusting for the effects of family size (number of children in a family) and the parent sizes. Z-scores of the children's sizes (Growth Indices) derived from polynomial growth modelling were taken as response variable(s) which analysed the data effectively. ANOVA shed the light on the effects of the factors on growth indices and MANOVA is shown to be an efficient tool to study the joint effect on the height, weight, and arm circumference indices. In order to explore the complex interrelated pattern of other factors influencing the growth of children and infants in Iran a further longitudinal study is suggested. PMID- 8492361 TI - Growth pattern of rural south Indian adolescent girls. PMID- 8492362 TI - Status of EPI in Nigeria: need for sustaining immunization coverage. PMID- 8492363 TI - Fasting during the last 3 months of pregnancy and effect on birth weight. PMID- 8492364 TI - Trends in health, nutrition, and socio-economic status in Nigeria, India, and Brazil (1960-1990). AB - The present study compared and analysed the nutritional and economic situations in Nigeria, India, and Brazil over the three-decades between 1960 and 1990. Intra country comparisons were undertaken for each country. The various indicators studied included among others the gross national product, total external debt, population, literacy, immunization, daily calorie intake, mortality, and life expectancy. It was noted that the economic situation influences the social and general health indicators of a country. Positive economic growth can lead to improved social development as well as diet and general health conditions. The opposite is also true, when economic growth is poor. The relationship between economic growth, and social and general health indicators is, however, not always applicable. This happens when the government fails to distribute incomes fairly; improvements in the country's social development, with nutritional and health indicators, does not occur. These findings call for a larger comparative study of the economic, social and health indicators for all the countries in the world. PMID- 8492365 TI - The Bamako initiative. PMID- 8492366 TI - Correlates of malnutrition among children under 2 years of age admitted to hospital in Yaounde, Cameroon. AB - A survey of health status, biodemographics, and use of health care services of all children under 2 years of age, consecutively admitted to the Baudeloque ward of the Central Hospital of Yaounde, Cameroon, was conducted over a 12-month period (1984). During the admission procedure, each child's mother or surrogate mother was interviewed and the child was weighted according to study protocol; additional data were collected by review of hospital records. A total of 669 children were recruited into the study sample; there were no refusals. Nutritional status was estimated by categories based on weight for age. Overall, 43 per cent of the sample were of normal weight-for-age, and 6 per cent, 19 per cent, and 32 per cent were categorized as having severe, moderate, and mild malnutrition, respectively. Multinomial logit modelling was used to identify independent correlates of mild, moderate, and severe PEM simultaneously. The study findings underscore the broad health benefits of immunizations. Furthermore, any prior contact of mother or child with the health care system appears to be associated with better nutritional status on hospital admission. Children with mothers employed outside the home may benefit particularly from health services outreach programmes. PMID- 8492367 TI - Nutritional status and risk of infection among Ethiopian children. AB - This is a prospective study on the possible association between protein energy malnutrition and risk of infection in a pastoralist and in an agricultural community in southern Ethiopia. A total of 425 children under 5 years of age were observed for 8 months. In general, malnourished children had a significantly higher incidence of diarrhoeal disease, even after controlling for possible confounding social, economic, and environmental effects, as well as for past history of illness. However, the extent of this association between nutritional state and morbidity differed between the two study populations. Thus, only wasting was associated with increased incidence of diarrhoeal disease among the pastoralist, whereas wasting, stunting, low weight for age, and low arm circumference all showed such an association in the agricultural community. Demographic and socio-economic characteristics as well as differences in the prevalence of stunting may explain this discrepancy. PMID- 8492368 TI - Epidemiology of perinatal loss in rural Maharashtra. AB - This study was carried out in a tribal block in Maharashtra in 1987. Socio economic and obstetric factors commonly known to be associated with unfavourable perinatal outcome were assessed by studying odds ratio, attributable risk, and stepwise multiple regression. Preference for traditional health care, long distance from health post, teenage pregnancy, inadequate schooling, hard physical work, first or fifth and subsequent pregnancy, certain antenatal, intranatal, and postnatal factors emerged as important causes associated with perinatal loss. PMID- 8492369 TI - Maternal nutritional status as a determinant of child health. AB - To determine the relationship between the nutritional status of the mother and that of the child, 339 children aged 3-36 months and their mothers in two urban hospitals and a community out-patient clinic, were studied. The weight and height of both children and their mothers were measured, and body mass indices (BMI) of the mothers were calculated. Socio-economic status, maternal educational level, and dietary information were recorded in a predesigned questionnaire. The child's nutritional status, as indicated by weight for age (as a percentage of NCHS median), was associated with the body mass index of the mother (P < 0.001), socio economic status of the family (P < 0.001), and breastfeeding status of the child (P < 0.005) in a multivariate analysis after adjusting for several prognostic factors. The results indicate that maternal nutritional status is a proximate determinant of a child's nutritional status and should be considered in programmes aiming at improving child health. PMID- 8492370 TI - Xerophthalmia, vitamin A supplementation and morbidity in children. AB - The relationship between ocular manifestation of vitamin A deficiency and children's anaemic/morbidity status as well as the efficacy of vitamin A prophylaxis in preventing these conditions was determined. The prevalence of xerophthalmia in morbid children with anaemia and history of worm infestation, measles, and diarrhoea was higher as compared to their non-morbid counterparts. The relative risk (RR) of anaemic children with eye signs was significantly higher (1.5), but the chances of having anaemia were similar in both vitamin A receivers and non-receivers. The RR of history of worm infestation, measles, and severe diarrhoea was 1.4, 1.0, and 1.2, respectively, in children with eye signs and 1.2, 0.8, and 1.3, respectively in children who did not receive vitamin A prophylaxis. The RR for occurrence of diarrhoea along with vitamin A deficiency was as high as 1.9. It appears xerophthalmia and anaemia co-exist and vitamin A supplementation helps in curbing these conditions among 1-6-year-old children. PMID- 8492371 TI - HIV-1 infection among malnourished children in Butare, Rwanda. AB - In order to investigate the relationship between human immunodeficiency virus (HIV-1) infection and protein-energy malnutrition (PEM), all 101 malnourished children who were admitted to the Department of Pediatrics of the National University Hospital between February and July of 1989 (median age = 2.5 years), and who were accompanied by their mother were screened for HIV-1 antibody. Mothers were also screened and interviewed. Mother-child pairs were followed-up 2 years later to determine mortality and clinical status. Fourteen per cent of malnourished children were HIV-1 seropositive. Only one seropositive child had a seronegative mother. This child had a history of multiple blood transfusions and injections. Among children above 15 months of age, HIV-1 seropositivity was more common among marasmic children than among malnourished children presenting with oedema at admission to the hospital. Also, HIV-1 infection was found more frequently among chronically malnourished children (low height for age and weight for age) than among acutely malnourished children (low weight for height). Mortality during the 2-year follow-up was 75 per cent among HIV-1 seropositive children and 23 per cent among HIV-1 seronegatives (mortality density ratio = 6.2; 95 per cent confidence interval = 2.2-17.4). Severe, chronic PEM should always alert health workers to the possible diagnosis of pediatric AIDS, and its implications for treatment and prognosis. PMID- 8492372 TI - Bacterial aetiology of acute lower respiratory infections in pre-school Nigerian children and comparative predictive features of bacteraemic and non-bacteraemic illnesses. AB - In a 9-month surveillance of the microbial agents causing acute lower respiratory infections (ALRI) in hospitalized preschool Nigerian children, 24 bacterial isolates were made from 22 (33 per cent) out of 66 blood cultures, including seven (70 per cent) of the 10 cultures from subjects with pleural effusion. Of the 24 positive isolates, Staphylococcus aureus accounted for 14 (58 per cent), Klebsiella pneumoniae for four (17 per cent), Streptococcus pneumoniae and Staphylococcus albus for two (8 per cent) each, and Haemophilus influenzae for only one case. Seven subjects had a mixed aetiology, comprising one bacteraemic case with measles and six with concomitant viral identifications. Sixteen cases, 10 (63 per cent) of whom were malnourished, had two or more pathogens, including 10 with multiple viruses. Bacterial isolates from the throat, were not significantly predictive of the ALRI aetiology. Overt malnutrition, empyema, and anaemia, were significantly commoner in bacteraemic cases (P < 0.03, 0.01, and 0.05), while rhinorrhoea and crepitations were each associated with the non bacteraemic ones. (P = 0.05 and < 0.05). A similar association was shown between rhinorrhoea, wheezing/rhonchi and the mixed aetiological group (P < 0.05 and 0.05, respectively). The case-fatality in bacteraemic subjects, was 9 per cent and was 2.1 times higher than that for non-bacteraemic cases, in whom a shorter mean duration of admission was recorded. In developing countries, the need for periodic local surveillance of ALRI pathogens, as a prerequisite for evolving rational antimicrobial policies, is emphasized. Our findings underscore the predictive importance of malnutrition as a risk-factor of severe bacteraemic ALRI, frequently associated with multiple pathogens. The relative usefulness of blood culture in identifying bacterial agents of ALRI is discussed. PMID- 8492373 TI - Volumetric blood flow measurement with color Doppler ultrasonography: the importance of visual clues. AB - Volumetric flow rates were obtained in an in vivo canine pulsatile flow model using color Doppler ultrasonography (CDUS) and timed collection (TC) over a range which included laminar and turbulent flow. CDUS demonstrated increasing flow disturbance as flow rates increased, with effects on velocity profile, diameter measurements, and flow symmetry. Data comparing CDUS and TC showed marked differences in laminar flow (regression: slope = 1.02; r2 = 0.93; mean error, 11%) and nonlaminar flow (slope = 0.53; r2 = 0.78; mean error, 26%). Assigning the angle of insonation precisely was crucial to measurement accuracy. CDUS quantitates volumetric blood flow with a reasonable degree of accuracy under laminar flow conditions. Visual clues provided by CDUS can help avoid errors associated with deviations from laminar flow. PMID- 8492374 TI - The lemon sign: not a specific indicator of meningomyelocele. AB - The association of the "lemon sign" with myelomeningocele has been well documented. This study was performed to determine if this sign is exclusive to myelomeningocele. The study population included all abnormal fetuses in our data base with this sonographically observed finding, from 1988 to 1991 (total of 23 cases). Twelve fetuses were found to have a myelomeningocele and six an encephalocele. Five fetuses with the lemon sign demonstrated a variety of structural anomalies not involving the neural tube. This sonographic finding appears not to be limited to cases of myelomeningocele. PMID- 8492375 TI - Umbilical artery and ductal blood flow velocities in patients treated with aspirin and prednisone for presence of anticardiolipin antibody. AB - Fifteen patients with previous pregnancy losses and positive plasma anticardiolipin antibody (ACA) were treated with prednisone (15 mg/day) and aspirin (80 mg/day). We measured Doppler velocimetries of umbilical artery and ductus arteriosus at intervals of 2 to 3 weeks starting from 20 weeks of gestation until delivery. Umbilical artery systolic/diastolic ratios (S/D) and maximum systolic velocities of ductus arteriosus did not differ from normal values. There were no poor outcomes in the treated group. ACA positive patients with previous poor pregnancy outcome when treated with prednisone and aspirin have umbilical artery and ductal flow velocities similar to those of the normal population. PMID- 8492376 TI - Pitfalls in the transvaginal sonographic diagnosis of ectopic pregnancy. AB - Transvaginal sonograms (TVS) of 40 adequately documented ectopic pregnancies were reviewed retrospectively. Difficulties that interfered with the accurate demonstration of the adnexal mass of the ectopic pregnancy were identified in 21 of these studies (52.5%). In three cases (7.5%) the ectopic pregnancy was visualized in an erroneous location. In 11 cases (27.5%), the ectopic pregnancy was overshadowed by coexisting pathologic findings, misinterpreted as a bowel segment or poorly demarcated from the adjoining ovary. In seven cases (17.5%), the adnexal mass of an ectopic gestation was completely over-looked on initial TVS. TVS in the women suspected of having an ectopic pregnancy must be performed meticulously and with due consideration to the pitfalls described. PMID- 8492377 TI - Sonographic diagnosis of ectopic pregnancy with endovaginal probes: what really has changed? AB - To evaluate the impact of endovaginal (EV) sonography in the diagnosis of ectopic pregnancy, a 2 year retrospective study was performed identifying 123 at-risk patients. Of these 123 women, 19 (15.4%) had a surgically proved ectopic pregnancy, only three (15.8%) of which were visualized directly at sonography. A confident diagnosis of an intrauterine pregnancy (IUP) was made at the initial scan in 74%, which contrasts with 58% diagnosed at the first transabdominal (TA) scan in an earlier study from this laboratory, thus confirming an improvement in diagnostic ability with EV transducers. This study has failed to confirm some findings of other workers, particularly that adnexal ring-like structures are visualized frequently in the presence of an ectopic pregnancy. No adnexal rings were observed in our 19 cases. The combination of an adnexal mass and free pelvic fluid was found to correlate best with the presence of an ectopic pregnancy. This study further emphasizes that a significant proportion (26.3%) of ectopic pregnancies have a normal EV sonogram at presentation. The group failing to demonstrate an IUP and showing no evidence of an adnexal mass or pelvic fluid (i.e., a normal pelvic sonogram) carried a 1:3 risk for the presence of an ectopic pregnancy, a result that is very similar to our data published before the introduction of EV technology. We conclude that, although it provides a significant improvement and refinement in the recognition of intrauterine pregnancies, EV scanning does not permit a confident diagnosis of ectopic pregnancy in many cases. PMID- 8492378 TI - Predicting aneuploidy in fetuses with cardiac anomalies: significance of visceral situs and noncardiac anomalies. AB - To determine whether the risk of aneuploidy in fetuses with cardiac anomalies is affected by abnormal visceral situs or coexisting noncardiac anomalies (NCA), were reviewed 125 cases in which a structural cardiac anomaly was detected by prenatal sonography. Forty-three of the 125 fetuses (34%) had an abnormal karyotype (31 autosomal trisomies, 12 other). None of the 13 fetuses with abnormal visceral situs had an abnormal karyotype, whereas an abnormal karyotype was present in 43 of 112 with normal visceral situs (P < 0.01, Fisher's exact test). The karyotype was abnormal in 33 of 52 (63%) with coexisting NCA and in only 10 of 73 (14%) without coexisting NCA (P < 0.001, chi-square). Therefore, among fetuses with structural cardiac anomalies, abnormal visceral situs is strongly predictive (100% in our series) of normal karyotype, whereas the presence of coexisting NCA significantly increases the risk of aneuploidy. These findings can help guide recommendations concerning prenatal karyotyping. PMID- 8492379 TI - Positive outcome of fetal intracranial teratoma. PMID- 8492380 TI - Lesions in the placenta. PMID- 8492381 TI - Resistance versus pulsatility index. PMID- 8492382 TI - Abnormally thickened rectal wall on transrectal sonography: rectal Kaposi sarcoma. PMID- 8492383 TI - Focus in glaucoma may change from keeping fluid out to letting fluid out. PMID- 8492385 TI - Middle-of-night airliner drama brings record number of patients to physician at remote site. PMID- 8492384 TI - Glaucoma gene mapped to chromosome 1. PMID- 8492386 TI - New tools ready for Chlamydia diagnosis, treatment, but teens need education most. PMID- 8492387 TI - The gender gap in selection of cardiac transplantation candidates: bogus or bias? PMID- 8492388 TI - From the Institute of Medicine. PMID- 8492389 TI - From the Centers for Disease Control and Prevention. Green tobacco sickness in tobacco harvesters--Kentucky, 1992. PMID- 8492390 TI - From the Centers for Disease Control and Prevention. Lyme disease--United States, 1991-1992. PMID- 8492391 TI - From the Centers for Disease Control and Prevention. Physician reporting of Lyme disease--Connecticut, 1991-1992. PMID- 8492392 TI - Rates of injury at day-care centers. PMID- 8492393 TI - Pressure ulcers: the benefits and costs of new therapies. PMID- 8492394 TI - Pressure ulcers: the benefits and costs of new therapies. PMID- 8492395 TI - Optimal use of blood tests for assessment of thyroid function. PMID- 8492396 TI - Foodborne illness in the 1990s. PMID- 8492397 TI - Foodborne illness in the 1990s. PMID- 8492398 TI - Critically ill cancer patients: benefit and expense. PMID- 8492399 TI - Smoking and lung function in elderly men and women. The Cardiovascular Health Study. AB - OBJECTIVE: To investigate relationships between cigarette smoking and pulmonary function in elderly men and women. DESIGN: Cross-sectional analysis of baseline data from a prospective, population-based study of risk factors, preclinical, and overt cardiovascular and pulmonary disease. SETTING: Defined communities in Forsyth County, North Carolina; Pittsburgh, Pa; Sacramento County, California; and Washington County, Maryland. POPULATION: A total of 5201 noninstitutionalized men and women 65 years of age and older. MAIN OUTCOME MEASURES: Pulmonary function; means of forced expiratory volume in 1 second (FEV1) and forced vital capacity and prevalence of low FEV1 levels. RESULTS: Prevalence of cigarette smoking was 10% to 20% and higher in women than men and in blacks than whites. Forced vital capacity and FEV1 levels were related positively to height and white race and negatively to age and waist girth. Age- and height-adjusted FEV1 means were 23% and 18% lower in male and female current smokers, respectively, than in never smokers but not reduced in never smokers currently living with a smoker. Smokers who quit before age 40 years had FEV1 levels similar to never smokers, but FEV1 levels were lower by 7% and 14% in smokers who quit at ages 40 to 60 years and older than 60 years, respectively. Lung function was related inversely to pack-years of cigarette use. Prevalence rates of impaired lung function were highest in current smokers and lowest in never smokers. Regression coefficients for the smoking variables were smaller in persons without cardiovascular or respiratory conditions than in the total cohort. CONCLUSIONS: Cigarette smoking is associated with reduced pulmonary function in elderly men and women. However, smokers who quit, even after age 60 years, have better pulmonary function than continuing smokers. PMID- 8492400 TI - Should unpublished data be included in meta-analyses? Current convictions and controversies. AB - OBJECTIVE: To identify the extent to which meta-analyses currently include unpublished data and whether editors, meta-analysts, and methodologists believe unpublished material should be included. DESIGN: This article describes two related studies: a literature review and a cross-sectional survey. SAMPLE SELECTION: For the literature review, we identified all articles indexed by the key word meta-analysis from January 1989 to February 1991 and determined whether unpublished material had been searched for, obtained, and included in the meta analyses. For the cross-sectional survey, we surveyed authors of these meta analyses, authors of articles addressing methodological issues in meta-analysis published during the same period, and editors of journals in which both types of articles were published. INTERVENTION: We asked the respondents about their attitudes concerning inclusion of unpublished data and publication of articles from which data had previously been included in a scientific overview. MAIN OUTCOME MEASURES: Inclusion of unpublished data and opinions about whether unpublished material should be included in overviews and whether prior inclusion of data in an overview should bear on publication. RESULTS: Of 150 meta-analyses, 46 (30.7%) included unpublished data in their primary analysis. Of authors surveyed, 85% responded. Of the meta-analysts and methodologists, 77.7% felt that unpublished material should definitely or probably be included in scientific overviews; this was true of 46.9% of the editors. A total of 86.4% of the meta analysts and methodologists and 53.2% of the editors felt that inclusion of data in a prior overview should have no bearing on full publication of original research. CONCLUSION: While inclusion of unpublished data in scientific overviews remains controversial, most investigators directly involved in meta-analysis believe that unpublished data should not be systematically excluded. The most valid synthesis of available information will result when meta-analysts subject published and unpublished material to the same rigorous methodological evaluation and present results with and without unpublished sources of data. PMID- 8492401 TI - Occupational injuries among working adolescents in New York State. AB - OBJECTIVE: To determine the number, distribution, determinants, and health consequences of occupational injuries among working adolescents in New York State. DESIGN: A retrospective, population-based analysis of New York State workers' compensation award data and the Annual Demographic File, a supplement to the US Bureau of the Census Current Population Survey. PARTICIPANTS: Adolescents, aged 14 through 17 years, who received workers' compensation awards for occupational injury from 1980 through 1987. MAIN OUTCOME MEASURES: (1) Numbers, types, and rates of occupational injuries in working adolescents by age, sex, industry, and occupation; (2) health consequences of injury, especially disability and death; and (3) secular trends in injury award rates. RESULTS: A total of 9656 adolescents were compensated for occupational injuries; 4201 compensated adolescents (43.5%) suffered permanent disability; 31 working adolescents died. The annual mean rate of compensated occupational injury was 28.2 per 10,000 adolescent workers. Rates were higher in males than in females and ranged from 8.2 per 10,000 in 14-year-old male workers to 46.8 per 10,000 in 17-year-old male workers. Highest rates by industry were seen in manufacturing (49.0/10,000 adolescent workers) and agriculture (46.2/10,000). Unskilled labor was the most dangerous occupation (52.3/10,000). CONCLUSION: Occupational injuries are a substantial and underrecognized contributor to the continuing epidemic of injury among adolescents. PMID- 8492402 TI - Neuropsychiatric effects of anabolic steroids in male normal volunteers. AB - OBJECTIVE: To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers. DESIGN: A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone. SETTING: An inpatient research unit at the National Institutes of Health. SUBJECTS: A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use. INTERVENTION: A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal. MAIN OUTCOME MEASURES: Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures. RESULTS: Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes. CONCLUSION: This is the first placebo controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids. PMID- 8492403 TI - Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems. PMID- 8492404 TI - Ethical, psychosocial, and public policy implications of procuring organs from non-heart-beating cadaver donors. PMID- 8492405 TI - Total quality management and physicians' clinical decisions. PMID- 8492406 TI - The rational clinical examination. Is this patient taking the treatment as prescribed? PMID- 8492407 TI - It's never too late to stop smoking. But how old are your lungs? PMID- 8492408 TI - Health care in Austria. Universal access, national health insurance, and private health care. PMID- 8492409 TI - [Results of the CCLSG high risk ALL 874 protocol in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group]. AB - One hundred and eighty eight children with acute lymphoblastic leukemia (ALL) were treated in a Children's Cancer and Leukemia Study Group high-risk ALL 874 study from April, 1987 to September, 1991. These patients received a four-drug induction regimen followed by the early consolidation regimen, cranial irradiation at 6 months of remission and three years of continuation therapy with rotational administration of four drugs. The patients were randomized into two regimens. In regimen A, the consolidation chemotherapy consisted of the intermediate dose cytosine arabinoside (Ara-C), cyclophosphamide (CPM) plus 6MP, and in regimen B, it consisted of high-dose Ara-C plus CPM. Regimen A was given to 106 patients and 82 patients received regimen B. The complete remission induction rate for regimen A and B was 89.4% (93/104) and 98.7% (78/79), respectively. The 3-year event-free-survival (EFS) rate was 70.6% for regimen A, which was higher than the 56.7% for regimen B. The 3-year EFS rate was 44.4% for the 53 patients with an initial leukocyte count > or = 10 x 10(4)/microliters and 72.2% for 132 patients with a leukocyte count < 10 x 10(4)/microliter. We considered that Ara-C plus L-asp, added to the conventional high-risk ALL 811 protocol, improved the prognosis of the high risk ALL patients. However, further intensive chemotherapy was required for improvement of the outcome of the patients with hyperleukocytosis (> or = 10 x 10(4)/microliters). PMID- 8492410 TI - [Follicular lymphoma associated with t(14;18)(q32;q21) chromosome translocation and bcl-2 gene rearrangement: report of a case]. AB - A 31-year-old Japanese male who complained of low-grade fever, fatigue and generalized lymphadenopathy had shown an increase in peripheral white cell count, and 84% of peripheral blood cell and 76% of nuclear bone marrow cells consisted of small cleaved lymphoblastic abnormal cells with or without barely visible nucleoli. Cytogenic study of cervical lymph node biopsy specimens showed a t(14;18)(q32;q21) chromosome translocation. Histologically the lymph node cells were classified according to the International Working Formulation as follicular small cleaved-cell lymphoma. Molecular analysis of DNA fragments of peripheral lymphocytes revealed both J-H gene and bcl-2 oncogene rearrangements. Immunophenotypes of peripheral lymphocytes, bone marrow cells and lymph node cells expressed a clonally distinct B-cell population bearing surface immunoglobulin-G, kappa-chain, CD-10, CD-19, CD-20, CD-21 and OKIa-1 antigens. We diagnosed this case as follicular lymphoma in the leukemic phase, PMID- 8492411 TI - [Effective danazol therapy for a patient with Evans syndrome]. AB - Danazol administered to a 66-year-old man with Evans syndrome, which was refractory to prednisolone therapy and pulse therapy with methylprednisolone. Danazol therapy produced an excellent and sustained improvement, increasing platelet counts and Hb concentrations. Recently, danazol therapy has been reported to be of benefit to severe idiopathic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). And this case marked a favorable effect also on Evans syndrome, which has both characters as ITP and as AIHA. The aim of this paper is to suggest that the administration of danazol has a positive effect on Evans syndrome and probably on other various thrombocytopenic diseases and syndromes, especially on refractory cases. PMID- 8492412 TI - [Cyclosporine therapy of adult onset Still's disease with disseminated intravascular coagulation]. AB - In April, 1991, a 61-year-old man was admitted to our hospital because of pancytopenia and disseminated intravascular coagulation (DIC). Five years prior to admission he had developed high fever, skin eruption and arthralgia which had been improved by antibiotics, but recurred. Steroid therapy was ineffective for pancytopenia and DIC. Laboratory findings were as follows: RBC count, 274 x 10(4)/microliters; WBC count, 470/microliters; Platelets, 6.4 x 10(4)/microliters; fibrinogen, 153mg/dl; FDP, 67.0 micrograms/ml; FDP-D.Dimer, 13040ng/ml; thrombin-antithrombin complex, > 60.0ng/ml; and plasmin alpha 2 plasmin inhibitor complex, 10.3 micrograms/ml. As we suspected adult onset Still's disease on the basis of clinical course, we treated him with methylprednisolone pulse therapy, which was, however, ineffective. leukocytopenia, thrombocytopenia and DIC improved after cyclosporine treatment. Since cyclosporine is known to be very effective to autoimmune diseases, we speculate that in this patient immunological mechanism may be involve in the pathogenesis of DIC. PMID- 8492413 TI - [Pulmonary disease as the chief manifestation of chronic graft-versus-host disease after allogeneic bone marrow transplantation]. AB - A 17-year-old man diagnosed as acute myelogenous leukemia (M5a) underwent allogeneic bone marrow transplantation from his HLA-identical, MLC non-reactive sister on the occasion of the second complete remission. On day 14 engraftment was confirmed by karyotypic expression. The patient had no evidence of acute graft-versus-host disease (GVHD), therefore cyclosporine A was discontinued on day 62. Having complained of cough and dyspnea by day 100, the patient was diagnosed as interstitial pneumonitis (IP) based on chest X-ray findings. However, no other typical signs of chronic GVHD were present except for modest abnormality of liver function. Since there was no evidence of infection on bronchofiberoscopic examination and prednisolone was very effective, it was considered that the IP might be pulmonary disease of chronic GVHD. It has been reported that HLA-DR which is not normally found, is expressed on epithelial tissues of the patient with GVHD. In this case alveolar epithelial cells were positive for LN-3 (anti-HLA-DR). In conclusion, pulmonary disease in this case may represent a possible manifestation of chronic GVHD, thus suggesting that the current case could provide information to ascertain the mechanism of chronic GVHD. PMID- 8492414 TI - [Cyclosporin for pure red cell aplasia caused rapid improvement of anemia and increase of CD4/8 ratio]. AB - Ciclosporine (CS) caused rapid improvement of anemia and increase of CD 4/8 ratio in two patients with pure red cell aplasia (PRCA). One case was a 45 year old female who were unresponsive to steroids, plasmapheresis and high dose cyclophosphamide, and another was a 61 years old man with diabetes mellitus (DM) without any treatment for PRCA. In both cases hemoglobin increased soon after the initiation of CS and CD 4/8 ratio also rose from 0.80 to 1.47 and 1.78 to 1.98, respectively. There was no side effects to interrupt the course of the therapy. CS seems to inhibit the production of cytokines such as IL-2 and IFN-gamma, and it damages the activated suppressor/cytotoxic T cells. CS is an effective drug for not only refractory cases but the first step therapy for the untreated patients. PMID- 8492415 TI - [Anemia and neutropenia due to copper deficiency during long-term total parenteral nutrition]. AB - A 33 year-old man with undiagnosed neuropathy showing mental retardation and involuntary movements has been nourished for a long period by total parenteral nutrition (TPN) because of frequent vomiting and repeated aspiration pneumonitis. After ten months' TPN, macrocytic anemia and neutropenia developed and iron preparation was administered without hematological improvement. Bone marrow examination revealed normocellular marrow without features of megaloblastosis and dysplasia. In some erythroblasts and immature myeloid cells, vacuoles were observed and mature granulocytes were reduced in the bone marrow. Both serum copper and ceruloplasmin were very low (12 micrograms/dl and 7mg/dl, respectively). Thus, oral administration of copper sulfate resulted in marked increase of reticulocytes and subsequent improvement of anemia and neutropenia within two months. Copper deficiency is a rare condition, but during an unusual nutrition such as TNP, hematological abnormality due to copper deficiency must be noticed to occur. PMID- 8492416 TI - [Idiopathic interstitial pneumonitis possibly associated with chronic graft versus-host disease]. AB - We described two cases of idiopathic interstitial pneumonitis (IP) after allogeneic bone marrow transplantation (BMT), who were successfully treated with prednisolone (PSL). A 40-year-old male with AML (M3) in the first remission (case 1) and a 36-year-old male with CML in chronic phase (case 2) were treated with BMT from HLA genotypically identical female siblings. Both patients were conditioned with busulfan (16mg/kg) and cyclophosphamide (120mg/kg), and given a combination of cyclosporin A and methotrexate to prevent acute GVHD (aGVHD). Engraftment of donor marrow was documented in both cases. Grade I of aGVHE developed in case 1 and no aGVHD in case 2. Both patients had clinical manifestations of chronic GVHD (cGVHD), which were followed by dyspnea and cough without fever 120 days (case 1) or 100 days (case 2) after BMT. Abnormal lung function tests and radiographic infiltrates indicated that patients developed IP, but causative microorganisms could not be detected in the bronchoalveolar lavage (BAL) specimens. Subjective symptoms disappeared in a few days after administering PSL (1mg/kg/day). Laboratory data also improved thereafter. These observations, including the development of radiographic infiltrates along with clinical manifestations of cGVHD, absence of febrile episodes, absence of causative microorganisms in the BAL specimens, and effectiveness of immunosuppressive drugs, suggested that idiopathic IP observed in our cases might be a manifestation of cGVHD. PMID- 8492417 TI - [Spontaneous splenic rupture in a case of non-Hodgkin's lymphoma]. AB - A 58-year-old man admitted to hospital as an emergency with pain in the left hypochondrium. The initial physical examination revealed hypotension, giant splenomegaly and ascites but no lymphadenopathy was found. Laboratory findings at admission included hemoglobin level of 9.2g/dl, leucocyte count of 22, 100/microliters with 2% of lymphoma cell and platelets count of 66,000/microliters. A presumptive diagnosis of ruptured spleen was made. Splenectomy was performed after 7 hours from admission. The spleen was infiltrated by malignant lymphoma. Three weeks after surgery, left neck and abdominal lymphoadenopathy were recognized, therefore systemic chemotherapy was started. The leukemic change was one of important factors for the mechanisms of spontaneous splenic rupture in malignant lymphoma. PMID- 8492418 TI - [Severe bleeding in a case of factor VIII inhibitor associated with intravascular lymphomatosis]. AB - A 70-year-old man was admitted to Jichi Medical School Hospital on October 1, 1990, complaining of spontaneous severe hemorrhage in his extremities. He had prolonged APTT value and normal PT value. Factor VIII level was markedly diminished, and a high titer of factor VIII inhibitor was observed. He was diagnosed as having idiopathic factor VIII inhibitor because of no sign of underlying disorders. He received prednisolone and immunosuppressants, subsequently with plasma exchange and bolous factor VIII, resulting in disappearance of the inhibitor. He was admitted again in February 1991, because of the reappearance of factor VIII inhibitor. In June, furthermore, bone marrow smears showed infiltration of atypical B cells, although no evidence of organomegaly and adenopathy was observed. Therefore, he was suspected to have primary bone marrow lymphoma. He received CHOP therapy, but he died of multiorgan failure. Postmortem autopsy demonstrated multifocal intravascular lymphomatosis with marked intravascular involvement of the lung, liver, kidney, adrenal glands, spleen and bone marrow. Lymph nodes were not swollen, showing little evidence of intravascular lymphomatosis. PMID- 8492419 TI - [Long-term maintenance of platelets by IFN alpha-2b in a case of chronic idiopathic thrombocytopenic purpura refractory to prednisolone therapy]. AB - A 63-year-old female with chronic idiopathic thrombocytopenic purpura refractory to prednisolone therapy was treated with interferon alpha-2b (IFN alpha-2b). Initially, the patient received 2 courses of short-course therapy in which 1.5 million IU and IFN alpha-2b was subcutaneously injected 3 times a week every other day for 4 weeks. During the first course, the platelet count rose from 1.0 x 10(4)/microliters to 12.4 x 10(4)/microliters 3 weeks after the beginning of the therapy, but the effect was transient. In the second course the platelet increasing effect was lower than that in the first course. Then, intermittent injections of 3 million IU of IFN alpha-2b once a week were subsequently begun. Consequently, the patient's platelet count has been maintained at 5 to 9 x 10(4)/microliters for more than 19 months since the beginning of intermittent IFN alpha-2b therapy. PMID- 8492420 TI - [Chromosomal abnormalities in Castleman's disease with high levels of serum interleukin-6]. AB - Chromosomal abnormalities in Castleman's disease with high levels of serum IL-6 were reported. A 69-year-old male was found to have superficial lymph node swelling and polyclonal hypergammaglobulinemia, when he was admitted to the department of otolaryngology for carcinoma of the tongue in July 1991. In December, he was referred to our department after completing radiation therapy. Laboratory examination revealed 7.7 g/dl hemoglobin, 10.8 g/dl total protein, and 56.0% gamma-globulin. Serum electrophoresis revealed polyclonal hypergammaglobulinemia and no Bence-Jones protein. Bone marrow aspirates showed an increase of plasma cells to 21.8%. Serum IL-6 was 252 pg/ml. Chromosomal analysis of cells in the lymph node showed a karyotype of 46,XY,t(7;14)(p22;q22). The lymph node histology showed marked hyperplasia of plasma cells at interfollicular areas. These plasma cells were stained with both anti-kappa and anti-lambda antibody. He was diagnosed as multicentric form Castleman's disease. Treatment with prednisolone and melphalan resulted in improvement of clinical findings such as anemia, lymph node swelling and hypergammaglobulinemia in concurrence with decrease in serum levels of IL-6. Since the IL-6 gene is located on 7p21-22, the translocation 7; 14 may be related to the high level of serum IL 6. PMID- 8492421 TI - [A case of Jordans' anomaly]. AB - A 71 year-old female with jordans' anomaly was described. Fat-containing vacuoles were observed in neutrophils, eosinophils, basophils, monocytes and lymphocytes of the peripheral blood, but not in erythrocytes and platelets. In the bone marrow they were also observed in myeloid cells including myeloblasts, erythroblasts and megakaryocytes. In the granulocyte series, numbers of vacuole containing cells and numbers of vacuoles increased as leukocytes matured. Histochemically, vacuoles were thought to contain neutral fat based on staining with Sudan III. However serum lipids showed no abnormalities. Both the reduction rate of NBT and the phagocytic activities for Candida albicans were normal. PMID- 8492422 TI - [Coexistence of essential thrombocythemia and gastric cancer]. AB - A 74-year-old man was admitted because of swelling, pain and ecchymosis in the night lower extremity. A blood analysis revealed that Hb was 11.8g/dl, WBC 37,600/microliters, and platelet count 137.1 x 10(4)/microliters. The NAP value was high. Bone marrow examination disclosed marked megakaryocytic hyperplasia. Chromosomal analysis revealed 47, XY, +9. Hemostatic data were within normal ranges, but the 2nd aggregation of platelet by ADP was diminished. The serum beta TG was 159, PF-4 56ng/ml, B12 1,100, UB12 BC 1,800pg/ml. Gastric fiberoscopy revealed gastric cancer and CT scan disclosed marked splenomegaly. Essential thrombocythemia (ET) coexisting with gastric cancer was diagnosed based on these examinations. He was treated with anti-platelet agents, busulfan and tegafur uracil, however thromboembolic symptoms suggesting central nervous system and peripheral vascular ischemia and gastrointestinal bleeding occurred. Among diagnostic criteria for ET established by the polycythemia vera study group, there is a category "No known cause for reactive thrombocytosis." The case reported here had gastric cancer which may have contributed to the elevated platelet count, however this case could be diagnosed as ET coexisting with gastric cancer because of the above various clinical signs and laboratory results. Although then are few reports of the coexistence of other malignancies in ET, there may be many more similar cases because of the age preponderance in ET. In order to diagnose ET more precisely, more strict diagnostic criteria are needed. PMID- 8492423 TI - [An autopsy case report of hemolytic uremic syndrome after allogeneic bone marrow transplantation]. AB - A 27-year-old male with acute lymphoblastic leukemia (L2) received allogeneic bone marrow transplantation on June, 7 1990. He was conditioned with cyclophosphamide, Ara-C and total body irradiation. GVHD prophylaxis consisted of cyclosporin and short term methotrexate. He was diagnosed as having hemolytic uremic syndrome (HUS) on the basis of microangiopathic hemolytic anemia, thrombocytopenia and renal dysfunction on day 224. Cyclosporin was discontinued and FFP was transfused and plasma exchange was performed. He died of heart failure and sepsis on day 582. Autopsy confirmed the findings of HUS. PMID- 8492424 TI - [Hematologic response to low dose natural interferon-alpha in a case of CML with myelo-megakaryoblastic crisis]. AB - A 59-year-old female with splenomegaly was admitted in November, 1989. Her WBC was 7,900/microliters with 51% myeloblasts and 10% megakaryoblasts. Analysis of the surface markers showed that 56.5% were CD13 positive and 66.8% carried platelet GpIIb/IIIa. The Ph1 chromosome was 100% positive. VPM therapy was started but proved ineffective, as was subsequent MCNU therapy. The patient was given intramuscular human lymphoblastoid interferon-alpha (1.2 million IU daily) for more than 20 months. She had improved to the accelerated phase after INF alpha therapy for 13 months. Thus there appears to be a relationship between INF alpha and myelo-megakaryoblastic crisis. PMID- 8492425 TI - [Mediastinal diffuse large-cell lymphoma with sclerosis diagnosed by needle biopsy]. AB - A 28-year-old woman was admitted to our hospital with cough. CT scan indicated a huge mass in the anterior mediastinum. A transcutaneous needle biopsy showed tumor cell infiltration and compartmentalizing fibrosis. The tumor cells were positive for CD20 and CD45, and JH rearrangement was evident. The patient was diagnosed as mediastinal diffuse large-cell lymphoma with sclerosis. The tumor responded to combination chemotherapy. It should be emphasized that mediastinal diffuse large-cell lymphoma can be diagnosed using a small specimen obtained by transcutaneous needle biopsy. PMID- 8492426 TI - [History of eosinophils research in the world and Japan]. PMID- 8492427 TI - [Growth and differentiation of eosinophils--special reference to IL-5 and its receptor]. AB - IL-5 is a 46 KDa glycoprotein secreted from activated T cells, and plays an important role both in the growth and production of eosinophils. Murine eosinophils have been reported to express high and low affinity receptors. The IL 5 receptor is composed of two membrane protein subunits, alpha and beta subunits. Both alpha and beta chain of mouse and human IL-5 receptor have been identified and sequenced. The alpha subunit is a 60 KDa protein which binds to IL-5 with low affinity. The beta subunit is a 130 KDa protein which does not bind to IL-5 by itself, but forms the high affinity IL-5 receptor in the presence of the alpha subunit. On the other hand, only a high affinity receptor population has been identified on human eosinophils. Affinity cross-linking experiments resulted in the identification of human IL-5 receptor on eosinophils with a molecular mass of 55-60 KDa. PMID- 8492428 TI - [Humoral regulation of eosinophilopoiesis by interleukin-3, granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-5]. AB - In this communication, the humoral regulation of eosinophil production by interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) or eosinophil differentiation factor (EDF) is described. IL-3 and GM-CSF supported early and intermediate stages of differentiation of eosinophilic progenitor cells. In contrast, IL-5 (EDF) primarily supported terminal proliferation and maturation of eosinophilic progenitor cells. Therefore, a combination of IL-3 plus IL-5, GM-CSF plus IL-5 or IL-3 plus GM-CSF plus IL-5 augmented proliferation and maturation of early and intermediate stages of eosinophilic progenitor cells. The signal transduction pathway, which explain this functional network among these three cytokines, will be elucidated in the near future. PMID- 8492429 TI - [Effect of cytokines on eosinophil differentiation and proliferation]. AB - IL-3, IL-5, and GM-CSF are eosinopoietic cytokines that induce the proliferation and differentiation of eosinophils. However, the regulatory mechanism of eosinopoiesis is largely unknown. A combination of IL-3 and IL-5 induces selective proliferation and differentiation of eosinophils from mononuclear cell fractions of human cord blood. IFN-gamma decreases the IL-3- and IL-5-induced eosinophil differentiation in a dose-dependent manner. IL-4 and IL-2 also decrease the IL-3- and IL-5-induced eosinophil differentiation. These observations indicate that IL-2, IL-4, and IFN-gamma have a direct or indirect inhibitory effect on eosinopoiesis. PMID- 8492430 TI - [Induction of gene (mRNA) expression of CD23, CD25 and CD4 on eosinophils by eosinophilopoietic growth lymphokines]. AB - The effects of IL-3, GM-CSF and IL-5 on the expression of CD23 (Fc(E)RII), CD25 (IL-2R/p55) and CD4 on an eosinophilic cell line (EoL-3) were investigated by flow cytometry. A separate incubation with IL-3, GM-CSF or IL-5, did not induce the expression of CD23, CD25, or CD4. However, a sequential incubation with IL-3, then with IL-3 and GM-CSF, induced a significant expression of CD23 and CD25. After a further incubation with IL-3, GM-CSF and IL-5, CD4 was then expressed, while CD23 and CD25 expression still increased. The kinetics of expression of CD11b were parallel to that of CD23, but the expression of the transferrin receptor (CD71) remained negative. Northern blot analysis revealed the presence of mRNA encoding CD23, CD25 and CD4 in EoL-3 stimulated by IL-3, GM-CSF and IL-5. Culture with GM-CSF induced the binding of radiolabeled IL-5 to EoL-3 cells, with an increased affinity after a sequential incubation with IL-3, GM-CSF and IL-5. These data indicate that IL-3, GM-CSF and IL-5, might be involved in the expression of functional markers on eosinophil membrane. PMID- 8492431 TI - [Expression of activation antigen CD69 on eosinophils]. AB - The antigen, CD69, has been shown to be expressed on activated lymphocytes. CD69 has also been shown to be associated with signal transduction process. Recently, we demonstrated the expression of CD69 on eosinophils at inflammatory sites. Whatever the disease, lung eosinophils obtained from the bronchoalveolar lavage fluid or pleural effusion expressed significant levels of CD69, whereas most peripheral blood (PB) eosinophils did not express CD69. Further, in vitro stimulation of PB eosinophils by IL-3, IL-5, GM-CSF and PMA induced CD69 expression on PB eosinophils. These findings suggest that CD69 expression on eosinophils is restricted to local inflammatory sites and CD69 may be a useful marker for activated eosinophils at inflammatory sites. PMID- 8492432 TI - [Expression of adhesion molecules on eosinophils in relation to cytokines and chemotactic agents]. AB - The functions of eosinophils in immunological reactions and their heterogeneity have recently generated a matter of great interest. Several characteristics of human eosinophil heterogeneity, as well as the existence of eosinophil subpopulations, called "normodense" and "hypodense", in diseases associated with hypereosinophilia, have been reported. Hypodense eosinophils can be distinguished by the increased expression of various membrane receptors including IL-5 receptor (J Exp Med 172: 1347) and various protein expression (J Immunol 142:4416). On the other hand, recently, adhesion molecules are considered to play an important role in inflammatory processes in allergic and immune reactions such as bronchial asthma. It was recently described that symptoms of bronchial asthma in animal model were in particular improved by means of anti-ICAM-1 (Intercellular adhesion molecule-1) monoclonal antibody (mAb). Thus, in thin study, we examined the characteristics of expression of adhesion molecules on human eosinophils obtained from hypereosinophilia (hypodense eosinophils). As results, high intensity expression of adhesion molecules (CR3, LFA-1 alpha, LFA-1 beta) on eosinophils obtained from patients with hypereosinophilia were observed. Furthermore, ICAM-1, which is ligand for LFA-1 molecules, was also expressed on eosinophils with hypereosinophilia. To extend our understanding of high intensity expression of adhesion molecules (CR3, LFA-1 alpha, LFA-1 beta, ICAM-1) on hypodense eosinophils, we examined whether chemotactic agents or eosinophilopoietic growth lymphokines (IL-3, GM-CSF, IL-5) is involved in adhesion molecule expression using an eosinophilic cell line named EoL-3. These characteristics of adhesion molecules on eosinophils were induced by some chemotactic agents and eosinophilopoietic growth lymphokines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492433 TI - [Eosinophil granule proteins (MBP, ECP, EPX/EDN, EPO)--a possible process of eosinophil activation and degranulation]. AB - From current information, a brief review was made on the basic properties of a possible process of eosinophil activation and degranulation. The "activated" eosinophils show the following characteristics: diminished cell density, morphologic alterations, increased surface receptors, heightened parasite killing, increased metabolic activity and prolonged survival. Immune complexes (secretory IgA, IgG, IgE) are known as potent triggering stimuli of eosinophil degranulation as well as complement fragments (C3b, C3bi). Cytokines (IL-5, GM CSF), PAF and peptides (substance P) act both as weak degranulation inducer and degranulation enhancer. Synergism between the two pathways, Ca2+ and protein kinase C, is now recognized as a common feature of control of secretion in eosinophils. PMID- 8492434 TI - [Induction of granule release by intracellular application of Ca and GTP gamma S in human eosinophils]. AB - The roles of Ca and G proteins in granule release from human eosinophils were examined using a patch-clamp technique in single cells. The morphological changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. The intracellular application of Ca, and GTP-gamma-S induced fusion of EPO containing granules with the surface membrane which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A in human eosinophils. PMID- 8492435 TI - [Eosinophil activation evaluated by using a anti-human secreted form of ECP antibody (EG2)]. AB - EG2 is a monoclonal antibody which recognize activated eosinophils, and the increased number of eosinophils stained by EG2 suggest activation of the disease. In bronchial epithelium of patient with asthma, not only EG2-positive eosinophils but CD25-positive T lymphocytes are increased, and support the theory that asthma is a nonsuppurative inflammatory disease of bronchial tree. Bronchial hyperresponsiveness of patient with asthma, which was assessed by a methacoline provocation test, was correlated significantly with the number of EG2 positive eosinophils in bronchial epithelium. Moreover, most of eosinophils infiltrated to bronchial epithelium in patient with fatal asthma were EG2 positive. The severity of acute asthma attack however did not correlate with EG2-positive rate of eosinophils, but significantly correlated with releasability of granules from eosinophils in sputum of patients with asthma indicated by BMK-13 staining. There are many reports that EG2-positive eosinophils participate in the pathogenesis of other allergic diseases, several types of collagen disease and cancer therapy. PMID- 8492436 TI - [The potential role and mechanism of leukotriene and platelet-activating factor in allergic disease]. AB - Eosinophilic accumulation in the airway is a prominent feature in patients with bronchial asthma (chronic desquamative eosinophilic bronchitis). Recently, arachidonic acid metabolite such as leukotriene, 15-HETE and PAF are proved to play an essential role as chemical mediators in the pathogenesis of bronchial asthma. A close relation is found between eosinophils activation and those mediators. The bronchoconstrictive leukotriene (LT C4, D4, E4) are generated mainly from eosinophils and mast cells, while the chemoattractive LTB4 is produced from neutrophils. Platelet activating factor (PAF) is postulated as a causative mediator of the eosinophilic airway inflammation and bronchial hyperresponsiveness because PAF attracts and activates preferentially eosinophils. Evidence that eosinophils have ability to produce PAF like other inflammatory cells suggests an autocrine mechanisms of the eosinophil activation by PAF. PMID- 8492437 TI - [Oxygen radicals]. AB - Oxygen radicals such as O2- and H2O2 induce bronchoconstriction and airway hyperresponsiveness in animal models. Eosinophil peroxidase (EPO)+H2O2+halide system cause damage of respiratory epithelium, in vitro. Damage to airway epithelium may decrease the release of epithelium-derived relaxing factor (EpDRF) and trigger an axon reflex with the release of neuropeptides, such as substance P. Activated human eosinophils can release various inflammatory mediators, such as oxygen radicals, eosinophil granule proteins and leukotrienes, in vitro. The degree of the damage of the bronchial epithelium and the number of infiltrated and activated eosinophils in the bronchial epithelium correlate with the level of airway responsiveness in bronchial asthma patients. Therefore, eosinophil-derived oxygen radicals may contribute to the epitherial damage and enhance airway hyper responsiveness in bronchial asthma. PMID- 8492438 TI - [Eosinophil-derived collagenase (metalloproteinase)]. AB - Collagenase is a highly specific neutral protease which acts by cleaving the collagen molecule into fragments, at a site three-quarters of the distance from the amino terminus. Collagenase has been assumed to be connected with the destruction of the pathological connective tissue which accompanies inflammatory conditions such as rheumatoid arthritis and interstitial lung disease. Despite the association of eosinophils with wound-healing and fibrotic processes, their collagenolytic ability has been poorly defined and it was not until 1984 that human eosinophils were shown to contain an enzymatic activity which degrades collagen. Eosinophils contain a metalloprotein that degrades types I and III collagens and no collagenolytic activity against types IV and V collagens is detected. Some experiments suggested that the eosinophil collagenase was different from neutrophil collagenase which cleaves type I collagen preferentially. Eosinophils may play a role in the alterations in connective tissue matrices seen in physiological and pathological states. PMID- 8492439 TI - [Inflammatory role of eosinophil in allergic reactions]. AB - A role of eosinophil is thought to be an inflammatory effect, although it had been believed that the cell has a protective role by blocking mediators from the mast cell. Eosinophils release several kinds of basic and cationic proteins following receptor-mediated activation. These mediators gradually lead to tissue damage of the bronchi, skin, nerve, heart and other general organs. Bronchial asthma and eosinophilic pneumonia as well as hyper-eosinophilic syndrome is based on this pathogenesis. Potent therapy, including steroids, will be needed for long terms in these diseases with tissue eosinophilia. PMID- 8492440 TI - [Mechanism of parasite killing by eosinophils in parasitic infections]. AB - Eosinophils kill a variety of helminth parasites and some protozoan parasites in vitro by antibody- or complement-dependent mechanisms. Nevertheless, direct evidence of in vivo parasite killing by eosinophils is scanty. In Angiostrongylus cantonensis infection in non-permissive hosts, however, the intracranial worms are killed by eosinophils in the cerebrospinal fluid, indicating that the cells are associated, not only with the protective immunity against helminthic infections, but also with the innate resistance of the non-permissive host. Moreover, eosinophils could be probably involved in the damage of host tissues, e.g., loss of Purkinje cells in the cerebellum of mice infected with A. cantonensis. A variety of basic proteins derived from eosinophil granules, such as MBP, ECP, EDN (= EPX) and EPO, and possibly active oxygen products, may be involved in the killing of parasites. PMID- 8492441 TI - [Type IV allergic reaction (delayed type)]. AB - In guinea pig system, we have shown that a T cell-derived eosinophil chemotactic factor (ECF) plays a role especially in delayed-in-time tissue eosinophilia. In Kimura's disease characterized by blood and tissue eosinophilia, OKT4-positive T cells from the patients spontaneously produce an ECF (LDECF-HES; pI 6) without any additional stimulation. A monocyte-derived factor with mw of greater than 100,000 induce LDECF-HES production from T cells. On the other hand, OKT4 positive T cells from patients with parasite infection produce another ECF (LDECF PD; pI 7-8) during mitogenic or antigenic stimulation. LDECF-PD production is selectively potentiated by ECF-potentiating factor derived from monocytes. Furthermore we have shown that the two ECF differ in their effects on eosinophil chemotaxis, eosinophil cationic protein release and Fc receptor expression. Recently we have established a T cell line, STO-2, constitutively producing 5 ECF with different pI (5, 6, 7, 8 and 9). These 5 ECF have different biological activities in eosinophil survival, Fc receptor expression and induction of specific eosinophilic granules. Comparison of chemotactic response of eosinophils from various patients with eosinophilia to respective ECF has revealed that eosinophils are heterogeneous in their chemotactic activity. PMID- 8492442 TI - [The role of eosinophil chemotactic factor in localized tissue eosinophilia by parasitic infection]. AB - Eosinophil chemotactic factors (ECFs) are thought to play an important role in the recruitment of eosinophils to parasitic inflammatory regions. ECF-A derived from mast cells, lymphokines from lymphocytes and ECFs from complements are well known as host-derived ECFs. On the other hand, ECF from parasites (ECF-P) and cytokines such as ESP (eosinophil stimulation promoter) and interleukin-5 are reported to be responsible for the eosinophil accumulation in parasitic inflammatory regions. In a series of our experiments using Anisakis larvae, we discovered a mechanism of eosinophil recruitment which could be accelerated by priming with ECF-P in parasite infected eosinophil phlegmon. PMID- 8492443 TI - [Morphological examination: immunohistochemical study--study for eosinophils in an autopsy case of asthma using monoclonal antibodies (EG1, EG2)]. AB - In order to investigate the activation of eosinophils in asthma, we performed an immunohistochemical study of the lung and bone marrow obtained from an autopsy case of asthma, using an eosinophil granule mAb (EG2) as a marker of activated secreting eosinophils. We found a large number of EG2-positive eosinophils in and around the small bronchioles and numerous EG2-positive pro-eosinophils in the bone marrow. In this paper, a method of immunohistochemical study using monoclonal antibodies (EG1, EG2) and the usefulness for the estimation of activated eosinophils in the inflammatory tissues is discussed. PMID- 8492444 TI - [The ultrastructure of human eosinophils studied by thin sectioning, rapid freezing and deep-etching technique]. AB - The crystalline structure of mature human eosinophils were observed, both by an ultrathin sectioning, rapid-freezing and deep-etching (RF-DE) technique. The crystals obtained with thin sectioning show parallel bands or square lattice structure with a periodicity of about 4 nm. By the RF-DE technique, most crystals show a staircase appearance and in the crystal parallel bands are observed with a spacing of about 4.4 nm. A square lattice structure is observed in a few granules. Since biochemical studies have revealed that the major basic protein (MBP) was localized in the crystal, the crystals can be considered to be crystalized MBP. Although it is known that the patients with hypereosinophilic syndrome have more hypodense eosinophils compared with the normal volunteer, no morphological differences was found in the crystals, between these two eosinophils. PMID- 8492445 TI - [Advance of the examination of eosinophil: methodology and clinical significance- morphological examination--electron microscopic examination by immuno-SEM]. AB - An index of IgG receptors on eosinophils by the use of immuno-SEM. The IgG (Fc) receptors on the eosinophils in hypereosinophilic patients were studied by the use of anti-IgG linked carboxylate modified latex particles. Eosinophils were separated into various cell densities by metrizamide discontinuous gradients. Eosinophils in each fraction were incubated with anti-IgG linked latex particles. Then eosinophils were observed by scanning electron microscopy. The number of latex particles attached to the eosinophils were considered to represent the number of IgG receptors in this study. The latex particles attached to the low density eosinophils were much more numerous than those attached to the high density eosinophils. This suggests that the number of IgG receptors on the eosinophils is correlated to the biological activity of eosinophils. PMID- 8492446 TI - [Advance in the method of eosinophil separation--separation of human eosinophils in density gradients and measurement of density distribution]. AB - To separate human eosinophils from peripheral blood, we used six discontinuous density gradients of Percoll solution (1.070, 1.080, 1.085, 1.090, 1.095 and 1.100 g/ml). Eosinophils isolated from patients with bronchial asthma or hypereosinophilic syndrome (HES) were shifted to the lighter density as compared with that from healthy subjects. Light-shift of density of eosinophils (hypodense eosinophils) was mimicked by several agents including chemical mediators such as histamine or platelet-activating factor (PAF), cytokines such as interleukin (IL) 3, IL-5 or GM-CSF. It has been reported that hypodense eosinophils survive, and the ability to generate leukotriene C4, superoxide anion or to secrete tissue injurious protein such as ECP or MBP augments as compared with that of normal density (normodense eosinophils). This separation method of eosinophils using a Percoll solution may contribute to accurate understanding a role of eosinophils in the pathogenesis of bronchial asthma or HES. PMID- 8492447 TI - [A new method for the isolation of peripheral blood eosinophils using flow cytometry (FCM)]. AB - Human eosinophils are known to exhibit autofluorescence, which allows the preparation of highly enriched eosinophil suspensions from peripheral blood of normal donors and bronchoaveolar lavage fluid, using flow cytometry (FCM). The sorted eosinophils were morphologically normal by light microscopy, the purity was more than 90% and the viability was more than 90%. The function of purified eosinophils was evaluated by chemotactic activity to platelet activating factor (PAF:10(-7) M) and recombinant human interleukin-5 (rhIL-5:10(3) ng/ml). Chemotactic activity was greater in purified eosinophils from patients with asthma than from normal subjects. Flow cytometric separation and analysis of eosinophils should thus, facilitate future studies of eosinophil heterogeneity and function. PMID- 8492448 TI - [Advance in eosinophil chemotaxis assay method--automatic count of migrated cells by the image analyzing system in the Boyden method]. AB - Eosinophils, which are prominent inflammatory cells in the asthmatic airway, are attracted to the airway by several chemoattractants. At present, eosinophil chemotaxis is studied employing the Boyden Millipore chamber system in vitro. In the Boyden method, the number of migrated cells are evaluated by direct microscopic observation of individual cells. This microscopic procedure usually requires much time and it is difficult to obtain objective results. Therefore, we have developed a new fractional measurement technique, using the image analyzing system connected with a color video camera and a computer for counting the eosinophils which have migrated into a filter. Using this system with the Boyden method, migrated cells were observed more objectively and quickly. Therefore, this image analyzing system with the Boyden method, may be a useful technique for the fractional measurement of migrated eosinophils in a sample mixture of eosinophils and neutrophils. PMID- 8492449 TI - [The measurement of eosinophil granule proteins]. AB - It has been known that eosinophilia in the peripheral blood or tissue participate in allergic inflammatory reactions and parasitic diseases. The function of eosinophils depend on the biological activity of the granule proteins. Four of these protein-MBP, ECP, EPO, and EDN have been known. There are some assumptions that the eosinophils might cause a tissue damage on examination of their specific protein. Therefore, the measurements of these granule proteins might clarify the pathogenesis of eosinophils related diseases. In this review, we introduce a convenient method for purification, quantitative measurement in serum, BAL and detection of localization in tissue by an immunofluorescence method for specific staining of eosinophil granule proteins. PMID- 8492450 TI - [The assessment of Eo-CSF and cytokines as eosinopoietic factor]. AB - Considerable attention has been paid to the possible role of eosinophils in the pathogenesis of allergic disease and it is highly important to examine the mechanism of this increase in eosinophils. Recently, several lymphokines, interleukin (IL)-3, IL-5, and granulocyte/macrophage-colony stimulating factor (GM-CSF), have been shown to act sequentially on eosinophil precursors to their multiplication and differentiation. To clarify the mechanism of the increase of eosinophils, these cytokines and eosinophil colony stimulating factor (Eo-CSF) must be measured. Eo-CSF is generally determined by colony formation methods, such as the methylcellulose method or liquid culture method. The detection and measurement of cytokines have traditionally been achieved by a lineage of committed cells and recently sandwich enzyme-linked immunosorbent assays (ELISA) have been developed for human IL-3, IL-5 and GM-CSF. PMID- 8492451 TI - [The trend of molecular biology study on eosinophils]. AB - Recently, many investigators have been interested in the study on eosinophil biology since genes association with eosinophils such as interleukin-5 or eosinophil granule proteins (EPO, ECP, EDN, MBP, and CLC), were isolated. However, the molecular basis for the commitment of progenitors to the eosinophil lineage has not been determined. The mechanism by which eosinophil-specific genes encoding primary and secondary granule proteins (e.g. ECP, EDN, EPO, MBP, and CLC) are expressed and regulated during eosinophilopoiesis is also unknown. In this paper, I described the characterization of genes encoding eosinophil granule proteins and the mRNA expression of GATA-1 binding transcription factor during eosinophil differentiation. PMID- 8492452 TI - [Eosinophil kinetics]. AB - The in vivo kinetics of autologous 111In-oxine labeled eosinophils were studied in 3 patients with reactive eosinophilia. Organ distribution and life span of 111In-oxine labeled eosinophils were evaluated. The disappearance curve of the labeled eosinophils showed two exponential components in all cases. Between these two factors, there was a slightly increase of radioactivity, suggesting the presence of recirculation. Radioactivity in the spleen, the liver and the bone marrow were observed 5 minutes after the infusion, suggesting the presence of marginal pool in these organs. Radioactivity in the spleen was increased rapidly during 1 and 24 hours after the infusion. Sequestration and/or destruction of increased eosinophils may exist in the splenic pool. The granulocyte turnover rate in eosinophilia was less than in CML or chronic neutrophilia. The results indicate that the migration of eosinophils is less active than that of neutrophils. PMID- 8492453 TI - [The eosinophil and bronchial asthma]. AB - Eosinophils have been observed in and around the wall of bronchi in bronchial biopsies and in bronchoalveolar lavage fluid from asthmatics. Early studies of eosinophils suggested that they might combat inflammation induced by type I hypersensitivity reaction. However, in the past two decades new information regarding the biology of the eosinophils has been obtained. There is now increasing evidence to suggest that eosinophils may play a key role in asthma by damaging respiratory epithelium, by generating LTC4 and PAF, and by releasing cytokines. This hypothesis is supported by the recent observations of a significant correlation between airway hyperresponsiveness and the magnitude of bronchial eosinophilia, and by the several observations of a coincident occurrence of late asthmatic response and bronchial eosinophilia. PMID- 8492454 TI - [Bronchial asthma pediatric field]. AB - The role of eosinophils and their activation products in the development of asthma in children has been reviewed, based on the recent data from our laboratory. The levels of the peripheral blood eosinophils and eosinophil cationic protein (ECP), and bronchial sensitivity to methacholine (PC20) were compared among three groups: Group A, mite-sensitive asthmatic children, Group B, mite-sensitive non-asthmatic children having the same level of IgE antibody against mite(Df) as Group A, and Group C, mite-insensitive normal control children. Group A had significantly higher eosinophil and ECP levels than Group B, and Group B had also higher levels than Group C. The PC20 values in Group A were significantly lower than those in Group B, and the values in Group B were also significantly lower than those in Group C. These results have suggested that activation of eosinophil is an important contributing factor for the development of asthma in children in addition to allergic sensitization. PMID- 8492455 TI - [Allergic bronchopulmonary aspergillosis (allergic bronchopulmonary fungal diseases)]. AB - Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disease caused by viable Aspergillus in a relatively large bronchus and by the type I and type III allergies against the fungus. The clinical findings are characterized by recurrent pyrexial attacks (fever, cough and mucopurulent sputum containing mucous plugs, numerous eosinophils and the fungus), radiological evidence of recurrent collapse and consolidation in different areas of the lung, a blood eosinophilia and elevated serum IgE levels. Fungi other than Aspergillus may cause similar allergological diseases. Therefore, they should be call allergic bronchopulmonary fungal diseases (ABPF). Many diagnostic criteria of the disease have been proposed by many different authors, but, a return should be made to the original report by Hinson et al, 1952. PMID- 8492456 TI - [Pulmonary eosinophilia]. AB - Pulmonary eosinophilia is a disease entity which is characterized by an increase of eosinophils in the bronchoalveolar lavage fluid or in tissue. While there are several disease states encountered in pulmonary eosinophilia, some have a definite cause and diagnosis, while others are of unknown etiology. The diagnosis of idiopathic eosinophilic pneumonia is given when other pulmonary eosinophilia with known cause and diagnosis are excluded. Simple pulmonary eosinophilia and chronic eosinophilic pneumonia are well established disease entities, but recent papers have clarified a new concept of acute eosinophilic pneumonia. In this article, the clinical features of three idiopathic eosinophilic pneumonias simple pulmonary eosinophilia as a self-limiting lung infiltrates, chronic eosinophilic pneumonia as a disease with longstanding symptoms requiring steroids administration and a tendency to relapse, and acute eosinophilic pneumonia as an acute respiratory distress which responds dramatically to steroids administration and without relapse after discontinuation of therapy are discussed. PMID- 8492457 TI - [A review of allergic granulomatous angitis (AGA) (Churg-Strauss syndrome)]. AB - We reported clinical features of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 2 males and 9 females with a mean age of 56.3 year-old. The age of the onset of bronchial asthma was high, and most of the patients had been suffered from frequent and severe asthmatic attacks during the period preceding the vasculitis. At the onset of the disease, patients showed a variety of vasculitic symptoms, including fever and neuropathy. Peripheral blood eosinophilia was universally seen. Three patients died of heart failure or central nerve involvement. Vasculitis ameliorated in 8 cases following steroid treatment. Discontinuing maintenance therapy with low-dose steroid resulted in a relapse in only one case. The significance and indication for long-term maintenance therapy should be further clarified. Based on these findings and previous publications, the clinical characteristics of CSS in Japan are discussed. PMID- 8492458 TI - [Kimura's disease (eosinophilic lymphfolliculoid granuloma)]. AB - Eosinophilic lymphfolliculoid granuloma was first described by Kimura et al. under the heading of "On an unusual granulation accompanied by hyperplastic changes of lymphatic tissue" in 1948. There after various terms have been used for this disease, such as eosinophilic granuloma and eosinophilic lymphfolliculosis. Ever since Iizuka et al. proposed the term Kimura's disease in 1959. This disease is a relatively rare condition. It usually occurs in the soft tissue of the head and neck regions and extremities, associated with eosinophilia and elevation of serum IgE. The main histopathological features are proliferation of lymphfolliculoid structures, granulation tissue with marked infiltration of eosinophiles and mast cells, and fibrosis. The etiology of this condition is, however, still unknown. We report the clinicopathology and immunohistochemical study of this disease. PMID- 8492459 TI - [Hypereosinophilic syndrome]. AB - Ten HES cases, which satisfied the Chuside criteria are reviewed. We found several types of HES--mild forms, often accompanied by edema, and more severe forms accompanied by vascular, lung and heart disorders. It is not necessary to treat some milder forms while the more severe forms often respond to large dose of prednisolone. Now that the diseases, which share a common hypereosinophilic factor, have been defined and HES is being seen in variants of various diseases, the concept of HES has reached a turning point. The administration of appropriate treatment to the particular individual case appears to be advisable. PMID- 8492460 TI - [Episodic angioedema with eosinophilia]. AB - In 1984, Gleich et al. originally reported a novel syndrome of episodic angioedema with eosinophilia. The syndrome is characterized by recurrent angioedema, urticaria, weight gain, elevated IgM levels, marked blood eosinophilia, and eosinophil infiltrates in the dermis. It has also been observed that activated CD4+ T cells are present in the dermis of patients with this syndrome, suggesting that T cell-derived cytokines especially IL-5 might be involved in the migration and activation of eosinophils in the skin. Indeed, it has recently been reported that serum IL-5 levels elevate during clinical exacerbation of this syndrome. However, it still remains to be elucidated what antigen periodically activates CD4+ T cells, what factor(s) determine selective migration of eosinophils into the skin, and so on. PMID- 8492461 TI - [Hematological malignancies with eosinophilia]. AB - Hematological malignancies accompanied by eosinophilia are reviewed in relation to chromosomal changes and cytokine production. Eosinophilia accompanied by hematological malignancies can be divided into two groups. In some myelogenous leukemias, including acute myelomonocytic leukemia with eosinophilia (FAB M4Eo), acute myeloblastic leukemia (FAB M2 t(8;21)) and chronic myelogenous leukemia, neoplastic cells themselves appear to differentiate into eosinophils. On the other hand, transformed tumor cells secrete some eosinophil-stimulating cytokines, including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor and these cytokines stimulate the proliferation of normal eosinophil precursors in some lymphoid malignancies, including some types acute lymphoblastic leukemia (especially with t(5;14)) or malignant lymphoma, including Hodgkin's lymphoma and adult T cell lymphoma/leukemia. PMID- 8492462 TI - [Skin disorders with eosinophilia]. AB - Many inflammatory or neoplastic dermatologic disorders have been recognized to be associated with tissue and/or blood eosinophilia. Furthermore, the degree of local and accompanying blood eosinophilia usually reflect the intensity and extent of the disease activity in various skin disorders. Recent advancement in the biology of eosinophils have also clarified the pathogenetic role of eosinophils in some diseases. In this issue, the dermatologic disorders with eosinophilia are reviewed. PMID- 8492463 TI - [Activated eosinophils in vernal keratoconjunctivitis]. AB - A recent study showed that eosinophil basic proteins in eosinophil granules tend to cause severe lesions in allergic disease. Eosinophil cationic protein (ECP) (an eosinophil basic protein), released from activated eosinophils, damages the epithelial mucosa. Vernal keratoconjunctivitis (VKC) always accompanies salient eosinophil infiltrations in the conjunctiva. To evaluate the role of activated eosinophils during VKC, we studied conjunctival specimens from VKC patients, using an immunohistochemical technique with monoclonal antibody (EG2) and electron microscope. We also determined ECP content in the patient tears. Immunocytochemical study showed a significant number of activated and degranulated eosinophils in the conjunctiva (giant papilla), including its epithelia and subepithelial tissue. Electron microscopy showed that the tear mucoid layer contained a number of exfoliated conjunctival epithelial cells with eosinophil granules. ECP content in the tears of these patients was 1361.4 +/- 1053.4 ng/ml, significantly higher than that of a normal subjects (< 20.0 ng/ml) (p < 0.01). These results suggest that the activated eosinophils and ECP contribute to the development of the lesion during VKC. PMID- 8492464 TI - [The role of eosinophil in nasal allergy]. AB - In this paper, the function of the eosinophil, activation of the eosinophil and degranulation of eosinophil granules are discussed. The in vitro mechanism of eosinophil-induced tissue injury has been reported previously. We have reported that most of the eosinophils in the inferior turbinate mucous membrane of nasal allergy were positive to EG2 and have also reported that extracellular deposits of EG2, MBP and EPO were mainly found in the superficial lamina propria. However, damage of the epithelia did not relate to the infiltration of EG2, MBP and EPO. The damage of the basement membrane could not be found. The concept of tissue injury induced by eosinophil, is controversial, and further study is required to elucidate the function of the eosinophil, in vivo. PMID- 8492465 TI - [Eosinophilic response in parasitic diseases]. AB - The increase of eosinophiles in peripheral blood and in the lesion is characteristic feature of many parasitic diseases. Those parasites which invade host organs generally cause eosinophilia of high degree. Thus, zoonotic parasites belonging to genuses gnathostoma, paragonimus and angiostrongylus etc. bring about continuous hypereosinophilic response due to lasting larval migration, but in contrast, those which migrate temporarily during the developmental stage in the host, cause transient eosinophilia, as in Loeffler's syndrome, due to round worms. In contrast, those parasites which live in the luminal organ and never invade tissues, may not cause eosinophilia. The variety of patterns in eosinophile response is outlined together with some clinical data. PMID- 8492466 TI - [Research on the liver]. PMID- 8492467 TI - [Investigation of gastric function and prevalence of Helicobacter pylori in non ulcer dyspepsia]. AB - One hundred and fourty four patients with non-ulcer dyspepsia (NUD), as defined by the working party of AGA in 1987, (67 men and 77 women, 16-76 years, mean age 42.9 +/- 1.2 years) and 34 asymptomatic controls (25 men and 9 women, 17-75 years, mean age 50.6 +/- 2.4 years) parameters of gastrophysiological function (gastric acid secretion, postprandial gastric emptying-acetaminophen method, serum gastrin levels and cutaneous electrogastrography (EGG)) and the prevalence of Helicobacter pylori (Hp) (histological and urease test of biopsy specimens) were investigated. Based on symptom patterns, there were 68 patients with dysmotility-like dyspepsia, 27 with ulcer-like dyspepsia, 17 with reflux-like dyspepsia, 6 with aerophagia and the 26 with nonspecific or idiopathic dyspepsia. The age distribution of NUD was predominant in the fourth decade, and the sex distribution was not significantly different. In general, hypersecretion of gastric acid and hypergastrinemia were rare in NUD patients. There was no significant difference in gastric acid secretion, basal and food stimulated serum gastrin levels and prevalence of Hp between the two groups. But 51 of 144 NUD patients (41.1%) had delayed gastric emptying (p < 0.05) compared to controls. Indeed gastric emptying was markedly prolonged in patients with dysmotility-like (58.1%) and reflux-like (42.9%) dyspepsia. On EGG, about a half of NUD patients showed evidence of bradygastria or tachygastria, in particular in the postprandial state, which was related to delayed gastric emptying. By chronic administration of cisapride, score of symptoms was significantly decreased and postprandial gastric emptying was significantly accelerated in delayed gastric emptying cases. We conclude that in NUD patients, in particular those with dysmotility-like dyspepsia, tests of postprandial gastric emptying and/or EGG are useful for investigation of gastric motor disorder and therapeutic effects of several prokinetic drugs clinically. PMID- 8492468 TI - [Macroscopic and histological studies on the gastric carcinoma having arisen from the cardiac gland mucosa--concerning to the esophageal invasion and the reliable surgical cut-line]. AB - Cardiac carcinoma is defined as the carcinoma whose center of the mucosal lesion is located at the area of the stomach within 2.0cm from the esophago-gastric junction. Histological and macroscopical examination was performed concerning to the frequency of macroscopic type, the direction of the mucosal invasion, the tendency of the submucosal invasion and the esophageal invasion by using these cardiac carcinomas. The objects of this study are a hundred and thirty-nine cases of cardiac carcinomas. The conclusions are as follows: 1) Depressed type (Type II c) in early carcinoma, Type Borrmann 2 and Borrmann 3 in advanced carcinoma are the most frequent form of macroscopic types. 2) The majority (87.7%) of the early carcinomas was situated at the lesser curvature and the posterior wall of the cardiac mucosa (Figure 1). 3) The early cardiac carcinoma had a tendency to invade in the mucosal layer along the esophago-gastric junction (Table 2). 4) The cardiac carcinoma was thought to invade into the submucosa in its early phase, comparing to the carcinoma on the other area of the stomach (Table 3). Twenty four out of thirty-five (68.6%) cases of cardiac carcinoma ranged from 11 to 20mm in diameter invaded into the submucosa (Table 3). 5) Twelve out of seventy-three (16.4%) of early cases and fifty-seven out of sixty-six (86.4%) of advanced cases showed the infiltration into the esophagus (Table 4, Figure 6). The reliable and surgical cut-line of the oral site can be established at the area over 11 mm in the distance from the oral margin of the mucosal invasion in the cases of early cardiac carcinoma, over 25mm in the cases of advanced differentiated type, and over 30mm in the cases of advanced undifferentiated type (Figure 6). PMID- 8492469 TI - [Cell kinetics of carcinoma originating from rat colitis induced by dextran sulphate sodium]. AB - Forty male Wistar rats were given 1% dextran sulphate sodium (M.W.: 50,000) as drinking water for six months. Well-defined elevated lesions were apparent in 12 (30%), showing the histological features of well differentiated adenocarcinoma. Focal atypical glands were histologically observed in 16 (40%). In vivo labeling of bromodeoxyuridine (BrdU) showed significant differences in S-phase cells among cancer (27.0 +/- 2.4%, atypical glands (20.8 +/- 5.9), regenerative mucosa (14.4 +/- 4.4) and normal mucosa (7.7 +/- 2.6), respectively (p < 0.01). BrdU labeling index of the upper part of the mucosal layer was smaller than that of the lower part in atypical glands, regenerative mucosa or normal mucosa, but they were similar in cancer. DNA aneuploidy was not detected either in cancer or in regenerative mucosa by flow cytometry. Ames test proved the low mutagenic potency of 1% DSS (Ames ratio, 2.1). In this experiment, colonic carcinoma seems to originate from mucosal inflammation itself. PMID- 8492470 TI - [Detection of point mutation of K-ras gene codon 12 in biliary tract and ampullary carcinoma by modified two-step polymerase chain reaction]. AB - The point mutation of K-ras gene at codon 12 was investigated in 11 cases of gall bladder carcinoma, 10 cases of extrahepatic bile duct carcinoma, 2 cases of intrahepatic bile duct carcinoma, and 4 cases of ampullary carcinoma by modified two-step polymerase chain reaction which employed paraffin embedded materials. The results revealed that there were point mutations in 6/11, 10/10, 2/2, and 4/4, respectively. Judging from the ratio of density of wild and mutant band, not all cancer cells in the tissue section contained the mutation. So it was suggested that the normal cells were initiated for the malignant transformation by ras gene mutations and then, selection might occur against cells containing ras mutations during progression of the tumor. Modified two-step polymerase chain reaction was markedly useful for detecting mutation even at low frequency among tumor cells. PMID- 8492471 TI - [A resected case of esophageal neurofibroma, and review of the Japanese literature]. PMID- 8492472 TI - [Beta-actin mutation in advanced human gastric cancer]. PMID- 8492473 TI - [Allergic granulomatous angiitis, AGA with perforation of jejunum report of a case and review of 12 cases in Japan]. PMID- 8492474 TI - [A case of colonic carcinoma with myelodysplastic syndrome]. PMID- 8492475 TI - [A case of hyperthyroidism appeared during interferon treatment for chronic hepatitis C]. PMID- 8492476 TI - [Effect of inhalation of tobacco smoke on the exocrine pancreas during caerulein induced pancreatitis in rats]. PMID- 8492477 TI - [A study to determine fecal lactoferrin in patients with ulcerative colitis]. PMID- 8492478 TI - [An epidemiological study of tuberculosis in the former coal mining area of Chikuho. II. A case-control study on the relationship between socioeconomic factors and tuberculosis]. AB - The authors conducted a case-control study on the relationship between socioeconomic factors and tuberculosis in the former coalmining area of Chikuho where tuberculosis incidence was high. The cases were 292 newly registered tuberculosis patients in Iizuka Health Center District, in the former coalmining area of Chikuho. Controls were randomly selected from resident cards, matched for sex, age, and place of residence. The results of comparing the cases with the controls were as follows: 1) Significantly more of the male cases had had long term employment in coalmining. Exposure to dust is likely to be associated with the high tuberculosis incidence in males aged 50 or over. 2) The cases showed significantly higher unemployment levels and lower educational levels. Among females, more of the cases were unmarried or divorced, and a significantly higher proportion were receiving welfare benefits. The high incidence of tuberculosis is probably related to a low socioeconomic level resulting from closure of coalmines. 3) No difference was observed in working hours, night shifts, smoking rate, and drinking habits. These factors are unlikely to be singly related to the onset of tuberculosis. PMID- 8492479 TI - [Abnormalities of calcium, phosphorous and vitamin D metabolism with proximal renal tubular dysfunction in subjects environmentally exposed to cadmium]. AB - Calcium, phosphorus and vitamin D metabolism were examined in 21 male and 13 female subjects with renal tubular dysfunction in the cadmium-polluted Jinzu River basin in Toyama prefecture, Japan. Multiple proximal renal tubular dysfunction was detected in all subjects showing increased FE beta 2-m and FFua, generalized aminoaciduria and renal glucosuria. Reduced ability of tubular reabsorption of phosphate resulted in hypophosphatemia in 31% of the women. Despite decreased tubular reabsorption of calcium, the level of serum calcium remained normal in all subjects. Serum 1,25-dihydroxyvitamin-D [1,25(OH)2D], which is produced in the proximal tubules through 1 alpha-hydroxylation from 25 hydroxyvitamin-D [25OHD], was normal or increased to more than 60pg/ml. The serum level of 1,25(OH)2D was inversely related to creatinine clearance in both the men (p < 0.05) and women (p < 0.01). Serum iPTH was slightly increased to more than 0.9 mg/ml, whereas the levels of other hormones, including 25OHD, calcitonin, thyroxine (T4) and triiodothyronine (T3) were normal. The serum alkaline phosphatase activity and serum osteocalcin concentration were significantly increased compared to those of controls in both sexes. Bone loss detected by the measurement of bone density was prominent in female subjects. These results support the hypothesis that the serum phosphate concentration is more important than the serum concentration of 1,25(OH)2D for abnormalities of bone metabolism in cadmium-induced renal tubular dysfunction. PMID- 8492480 TI - [Investigation of subjective symptoms among visual display terminal users and their affecting factors--analysis using log-linear models]. AB - In order to evaluate factors affecting visual and musculoskeletal symptoms by visual display terminal (VDT) operation, a questionnaire survey was conducted among clerical workers in Chiba university. The results were as follows: 1) Of these workers, 81.9% engaged in VDT operation. For most of the subjective symptoms, the prevalence rates tended to increase with the degree of VDT use. 2) These complaints were combined to give visual and musculoskeletal symptom scores. Both of the scores were higher among females than males, and the musculoskeletal symptom score was significantly higher. No difference was found in regard to age. 3) Analysis using log-linear models was performed to evaluate the effects of sex and age. The results showed that the visual and musculoskeletal symptom scores were significantly higher among the workers operating VDTs for one or more hours per day than among those who did not operate them at all. Analysis of the effects of VDT workloads revealed that VDT use for five or more days per week significantly increased the prevalence rates of both symptoms. Their use for less than four days per week affected neither of the symptoms. With regard to operating time per day or length of VDT use, no differences were found. 4) This investigation suggested that the VDT workloads were not so heavy and that the effects on each symptom were minor among the subjects of the present survey. However, it is important that consideration be given to ensure that the workloads for workers who operate VDTs every day not be too heavy. PMID- 8492481 TI - [Relationship of body-composition types to physical fitness performance for college women]. AB - The purpose of this study was twofold, 1) to classify the body composition of college women into certain types by combining percent body fat, and lean body mass per unit of height and 2) to clarify the characteristics of physical fitness performance in each group, because we have as yet no reports on physical fitness in such a way. The subjects were 205 college women (average age 19.1) in Morioka, Iwate, Japan, and we collected data on body forms and physical fitness performance of subjects in 1989 and 1990. We calculated body density by the SUZUKI-NAGAMINE skinfold thickness method for Japanese, and also % FAT by the BROZEK formula. In order to check significant differences of mean values for each type, we employed the t-test, and a statistically significant level of 0.05. The findings were as follows: 1. We classified the body composition of college women into 9 types: Aa, Ab, Ac, Ba, Bb, Bc, Ca, Cb, Cc by combination of % FAT and unit LBM. Type Aa has much more % FAT and unit LBM, while type Cc has much less % FAT and unit LBM. We observed that each type has a particular body form; for example, type Aa students generally have average height but are heavier, whereas type Cc students are usually shorter and lighter. 2. Type Ba showed the best physical fitness performance of the 9 types. This type has a body composition of average % FAT and much more unit LBM. Type Ab, with much more % FAT and average unit LBM followed type Ba.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492482 TI - [Digit preference in birth weight data of obstetric facilities]. AB - An investigation on instrumentation of birth weight in obstetric facilities was made in the northern part of Fukuoka Prefecture from March 1989 to January 1991. A distribution of 3000 cases from 100 facilities was analyzed for the purpose of clarifying the reliability of the data. The following results were obtained. 1) Birth weights measured by analogue scales (1530 cases) showed digit preference in all distributions of the whole, the lower three digits and the lower two digits. But those measured by digital scales (1470 cases) did not show any distortion in these three distributions. 2) There were significant differences among mean birth weights calculated from the intact data, and 50g-, 100g- and 500g-interval frequency histograms in analogue scales (p < 0.01). But in digital scales there were no significant differences among mean birth weights. Rounding error was supposed to be one of the main causes of this discrepancy. Digital scales are superior to other types of scales because they do not show distribution distortion of the data. The reliability of the birth weight data is different among the types of scales. We have to consider which type of scale is used when we refer to annual changes or differences among areas in mean birth weights. PMID- 8492483 TI - [Secular changes of the mean birth weight in Japan during the past 20 years (single births, 1969-88)]. AB - Using vital statistics (1981-1988) of the Japanese government, the mean birth weight (MBW) classified by sex was calculated from a birth weight distribution of the single births with 500g intervals for all Japan, prefectures and regions. These MBWs were linked with the MBW of 1969-1980 in our previous reports (Ref. 1) 2)). The MBWs of single births for twenty years (1969-1988) were investigated and it was pointed out that the MBWs classified by area (all Japan, prefectures and regions) were on the decrease recently and that the areal differences of the MBW were becoming large. For all Japan a secular change in the MBW was discussed for the term of a standard deviation, a skewness, a kurtosis, and relative frequencies of less than 2500g (weight class 1), those from 2500g to 3999g (weight class 2) and those of 4000g or more (weight class 3). These investigations revealed that birth weights of Japan have had a tendency to have a small standard deviation, a negative skewness, and a large kurtosis. Weight class 1 decreased until 1976 and increased after this year. Weight class 2 was on the increase up to 1988, and weight class 3 increased until 1973 and decreased afterward, as if it were accompanied by the MBW. For the purpose of confirming the contribution of each weight class to the annual change of the MBW, an analytical method for the weight frequency distribution was proposed as follows. Let M, M', pi and pi' represent the MBW of a given year (year A), the MBW of an another year (year B), the relative frequency of the i-th weight class in year A and that in year B, respectively. Suppose that M(i)'' represents the MBW when only the i-th weight class has pi as a relative frequency even in year B. Then, as the result of a fairly simple calculation, the difference between the MBW in year A and that in year B, M'-M, is obtained as follows; M'-M = sigma (1-pi') (M' M(i)''). Therefore, the amount (1-pi') (M'-M(i)'') is able to be considered as a share of the i-th weight class in relation to the difference of M'-M. Accordingly, the share proportioned to the summation of the absolute amount [formula: see text] may represent the degree of the contribution of the i-th weight class to the difference, M'-M.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492484 TI - [Correction of the mean birth weight calculated from a frequency distribution (Japan, single births, 1969-88)]. AB - Recently the mean birth weight (MBW) of Japan is on the decrease. This phenomenon started in 1976 and continues up to the present as of 1988. Various factors accounting for this phenomenon have been considered and discussed by several researchers. They were interested in social, cultural and economic factors as well as factors influencing community health status. Although the above factors seem to be important, one problem connected with calculation of MBW is worth discussing. The MBW was calculated from a frequency distribution because of a limitation of the source material. The accuracy of calculation of statistics from a frequency distribution depends on the assumption that few frequencies fall on boundaries, but birth weight measurements are apt to fall on figures having 0 at the end because of the properties of weighing scales. Suppose that the exact weight of an infant is 2996g. If his weight is read to the nearest figure having 0 at the end by rounding, it is recorded as 3000g on the birth certificate. Then, in a frequency distribution whose class interval is 500g, his weight is treated as 3250g in calculation of the mean. But some improvements of the methods of weighing, for example, utilization of a scale displaying a digital value of weight may result in a greater chance that his weight is recorded as 2996g. Then, in the same frequency distribution, his weight is treated as 2750g in calculation of the mean. Therefore, an improvement of the method of weighing produces the phenomenon that MBW decreases even if all the original birth weights did not change. Exact relative frequency, recorded as just 2500g, that is mentioned secondarily in the Vital Statistics of Japan has been decreasing consistently since 1969. This year is the oldest in the above source having frequency distributions of single birth infants. This fact shows that methods of weighing have been improved as the years pass. In this paper we tried to correct MBW by using the relative frequency recorded as exactly 2500g. Two kinds of widths where rounding would be executed were estimated from a frequency polygon. We obtained the following results. 1) The correction equation is represented as ld approximately; where l is a class interval (500g in this paper) and d is calculated by d = Q/(pa + pa+1 + Z) as a mean value in a certain sense and by d = 2Q/(pa + pa+1 + Z) as a maximum value.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492485 TI - [An epidemiological study of tuberculosis in the former coal-mining area of Chikuho. I. An analysis of newly registered tuberculosis patients in Iizuka Health Center District]. AB - To clarify risk factors and groups at high risk of tuberculosis, a study on tuberculosis was conducted in the former coalmining area of Chikuho, where the death rate from tuberculosis was high. The authors analysed 701 newly registered tuberculosis patients during the 5 years from 1982 through 1986 in Iizuka Health Center District in the Chikuho area, studied the geographical distribution of tuberculosis incidence in Fukuoka Prefecture, and compared the trends of tuberculosis incidence in Iizuka Health Center District, all Japan and Fukuoka Prefecture. The results were as follows: 1) The incidence of tuberculosis in Iizuka Health Center District was higher than those both in all Japan and in Fukuoka Prefecture. The incidence in Iizuka Health Center District has not decreased since 1981. Therefore, the difference in tuberculosis incidence between Iizuka Health Center District, and all Japan and Fukuoka Prefecture has gradually become greater. The incidence of tuberculosis in 1986 was 81.6 (per 100,000) in Iizuka Health Center District, 58.1 in Fukuoka Prefecture, 46.6 in all Japan. 2) A specific pattern was observed in the geographical distribution of tuberculosis incidence in Fukuoka Prefecture. A high incidence was concentrated in the former coalmining area of Chikuho. 3) The positive rate of tubercle bacilli (38.8%) was the same as that in all Japan. However, the positive rate was higher in age groups 10-49 than that in all Japan. 4) A total of 83.5% of tuberculosis cases were detected when visiting doctors, mainly with complaints of cough, fever and sputum. Only 6.9% of the patients were detected by screening examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492486 TI - [Pulmonary artery reconstruction for extreme tetralogy of Fallot and similar complex heart diseases before cardiopulmonary bypass]. AB - It is sometimes difficult to repair the pulmonary artery in extreme tetralogy of Fallot and other similar complex heart diseases, such as pulmonary atresia with major aorto-pulmonary collateral arteries, because of their complexity. Therefore, cardiopulmonary bypass takes longer in these patients than in those with usual tetralogy of Fallot. We undertook reconstruction of the pulmonary artery in 4 cases of extreme tetralogy of Fallot and other similar complex heart diseases before cardiopulmonary bypass. We investigated the cardiopulmonary bypass time in these patients and compared it with that in patients with usual tetralogy of Fallot. There was no significant difference in cardiopulmonary bypass time between the two groups. In the 4 extreme cases, the postoperative course was uneventful. We conclude that this attempt reduced the cardiopulmonary bypass time and facilitated the surgical correction. PMID- 8492487 TI - [Coronary artery bypass surgery in patients with poor left ventricular function]. AB - As the indications for coronary artery bypass grafting (CABG) among patients with poor left ventricular function remain incompletely defined, We undertook the study to assess the results of CABG surgery for a group of such patients. We retrospectively reviewed the clinical features and outcome for 7 patients with poor left ventricular function defined as an ejection fraction below 0.3 who underwent CABG. The mean age of the patients was 63 years (range, 38 to 78 years), and 4 were 70 years of age or older. All patients had history of previous myocardial infarction, and all had left main trunk stenosis or left main equivalent stenosis. The patients underwent CABG with three to six distal anastomoses (mean, 4.3/patient), the internal thoracic artery could be used in all patients, for one or two distal anastomoses (mean, 1.6/patient). Combined coronary endarterectomy was performed in 2 patients. With the exception of one 78 year-old patient with renal failure who died during the early postoperative period, all patients showed marked postoperative improvement in cardiac function. Cardiac catheterization and exercise stress test studies revealed significant improvement in left ventricular function and exercise tolerance in these six patients. These results suggest that excellent results can be obtained with CABG surgery in patients with poor left ventricular function when the viability of the myocardium in the bypassed area has been confirmed. PMID- 8492488 TI - [Surgical treatment of thoracic and thoracoabdominal aneurysm during partial cardiopulmonary bypass]. AB - We operated on 3 patients with thoracic or thoracoabdominal aneurysm using partial cardiopulmonary bypass with right atrial drainage. The first patient was in the preshock state with severe chest and back pain. The aortography and enhanced computed tomography showed a thoracic aneurysm of 70 mm in maximum diameter ruptured into the extrapleural space and an emergency surgery was performed. The second patient was also in the preshock state with chest and back pain. The enhanced computed tomography showed a thoracoabdominal aneurysm of 120 mm in maximum diameter ruptured into the bilateral pleural spaces and an emergency surgery was performed. The third patient had a thoracoabdominal aneurysm of 60 mm in maximum diameter with a low pulmonary function. In all 3 cases, a perfusion cannula was inserted in the femoral artery and a drainage cannula was placed in the right atrium through the femoral vein. In the first case, an additional perfusion cannula was inserted into the axillary artery in order to secure the cerebral flow even at the time of intraoperative massive bleeding from the aneurysm. In all 3 cases, the approach for aneurysm was through spiral incision and aneurysms were replaced by graft inclusion technique. All 3 patients had an uneventful postoperative course and are doing well. In surgical treatment of thoracic and thoracoabdominal aneurysm, usefulness of partial cardiopulmonary bypass using right atrial drainage was discussed. PMID- 8492489 TI - [Surgical treatment of ventricular septal defect associated with Down syndrome]. AB - Twelve patients with ventricular septal defect with Down syndrome (Down group) underwent cardiac surgery. As they had pulmonary hypertension (Pp/Ps > or = 0.5), we chose twenty patients who had pulmonary hypertension (Pp/Ps > or = 0.5) with ventricular septal defect without Down syndrome as control group. After cardiac surgery, Pp/Ps in Down group decreased significantly from 0.81 +/- 0.14 to 0.48 +/- 0.25 (p < 0.01). Cardiac index (l/min/m2) between 24 hours after operation was 3.3-3.8 in Down and 4.1-4.8 in control group (NS). Oxygenation index (mmHg) between 24 hours after operation was 211-266 in Down and 230-314 in control group (NS). Eleven out of 12 patients in Down group had good operative result. One patient was complicated with post-operative pulmonary hypertensive crisis. Low output syndrome and death were not encountered in Down group. We were satisfied with operative results and encourage surgical treatment for ventricular septal defect with Down syndrome. PMID- 8492490 TI - [The effect of LDL-apheresis on the long-term prognosis of hypercholesterolemic patients with coronary artery bypass grafts: a multicenter study]. AB - Hypercholesterolemia is well known as a risk factor which had been shown to affect the long-term prognosis after coronary artery bypass grafting (CABG). The data were collected from multi-institutions documenting the long-term results of CABG in 61 hypercholesterolemic patients who received LDL-apheresis. Mean post CABG period was 50 +/- 34 (+/- SD) months. Mean period of therapy by LDL apheresis using Liposorber system after CABG was 25 +/- 17 months with a frequency of once per 2.6 +/- 1.3 weeks. Before initiating LDL-apheresis mean serum cholesterol (TC) and LDL-cholesterol (LDL-C) were 327 mg/dl and 261 mg/dl, respectively. With combined LDL-apheresis and lipid-lowering drug therapy mean TC and LDL-C were reduced to 247 mg/dl and 177 mg/dl immediately pre-apheresis and 106 mg/dl and 60 mg/dl immediately post-apheresis, respectively. Two of 61 patients had PTCA post CABG. Percent free from cardiac event during the long-term period post CABG as calculated by the life-table method was 97% at 3 years and 94% at 4 years and thereafter. While number of the patients is still small, the aggressive cholesterol-lowering therapy by LDL-apheresis is suggested to improve the prognosis of hypercholesterolemic patients with bypass grafts. PMID- 8492491 TI - [Management of the severe calcified ascending aorta during coronary bypass surgery]. AB - The best management of the calcified ascending aorta during coronary surgery has not established. Clamping of the calcified aorta causes cerebral embolism, aortic rupture and laceration as a lethal complication. Recently we had two successful cases of surgical treatment and these were treated by "Non-touch aortic technique". The femoral cannulation and ventricular fibrillation with moderate hypothermia or circulatory arrest will reduce the risk of coronary bypass surgery in the calcified aorta. PMID- 8492492 TI - [Temporary pacemaker for cardiac operation]. AB - For temporary pacing during open heart surgery, we made a device with a permanent VVI pacemaker by simply fixing a lead to the connecting plug. It is easy to make this device, which allows for beginning pacing quickly, and it dose not interfere with the operation. PMID- 8492493 TI - [Introduction of intra-aortic balloon pumping catheter through left subclavian artery guided by trans-esophageal echocardiography]. AB - It is very difficult to insert an intra-aortic balloon pumping catheter into the descending aorta through the subclavian artery by the blind technique. But the technique with the guidance by trans-esophageal echocardiography to introduce the balloon into the descending aorta was simple and useful. PMID- 8492494 TI - [Removal of infected transvenous electrodes requiring cardiopulmonary bypass or extraction sheath]. AB - Infection of four transvenous pacemaker electrodes were experienced in three patients and removed them using different techniques. The first patient had two infected electrodes. One was removed by direct traction and the other required cardiopulmonary bypass for its removal. In the second patient, one electrode was removed using a new extraction system called 'Lead Removal Kit' without thoracotomy. In the third patient, the kit was used during cardiopulmonary bypass. All these patients survived and none had recurrent infection. Our experiences proved that this Lead Removal Kit can minimize the risks for the removal of the infected pacemaker electrodes. PMID- 8492495 TI - [A blind point of vent catheter: air aspiration]. AB - We experienced a case of saphenous vein air embolism after coronary artery bypass graft, in which case we used vent catheter kept in the left atrium. Though it was considered that air bubbles were never aspirated through vent catheter, we speculated that the origin of air bubbles must be the vent catheter. And we made an experiment on the motion of air in the vent catheter using a model of left heart composed with soft reserver (atrium) and pulsatile pump (ventricle). When the pulsatile pump was arrest, the air bubbles were never aspirated from the vent catheter to the soft reserver even if we vented with strong negative pressure. But, when the pulsatile pump was in motion and the left atrium was vented with some negative pressure, some leaks of air bubbles were recognized. So we must pay much more attention to the degree of venting when the heart is in motion. Sometimes we use overpressure safety valve composed with vent catheter, but measured left atrial pressure showed that decreased left atrial pressure was only 2 mmHg. So its use should be restricted in the patients with good ventricular function. PMID- 8492496 TI - [Surgical treatment of unroofed coronary sinus]. AB - We have experienced four cases of unroofed coronary sinus. Three cases were partial forms and one case was a complete form. Two of them were successfully diagnosed before operation. Surgical viewpoints were discussed. In the absence of LSVC, the coronary sinus defect may be simply closed. In the cases with PLSVC, several types of repair were discussed. It has been reported that this defect is usually associated with simple or complex cardiac malformations, including tricuspid atresia or tetralogy of Fallot. In our case with TA, oversight of this anomaly before and during operation resulted in the urgent reoperation. A surgeon should always keep in mind this anomaly, even if the coronary sinus is not large. PMID- 8492497 TI - [Experience with radical operation for lower thoracic esophageal cancer through left diagonal thoraco-laparotomy and right posterolateral thoracotomy]. AB - Two cases were reported in which subtotal thoracic esophagectomy, total gastrectomy, splenectomy and distal pancreatectomy was performed for the lower thoracic esophageal cancer through right diagonal thoraco-laparotomy and left posterolateral thoracotomy. Reconstruction was done with the intrathoracic esophagojejunostomy. Extubation could be done on the 1st postoperative day, and postoperative course was uneventful. It was thought that the approach with left diagonal thoraco-laparotomy and right posterolateral thoracotomy was useful for the easy and complete lymph node dissection from the middle mediastinum to the intra-abdominal cavity. PMID- 8492498 TI - [A case of discrete type of subpulmonary stenosis]. AB - We reported a 8-year-old girl having discrete type of subpulmonary stenosis. This patient was associated with atrial septal defect (ASD), valvular pulmonary stenosis, and persistent left superior vena cava (PLSVC). The incidence of this type of subpulmonary stenosis is less frequent than that of subaortic lesion. ASD was closed by the autologous pericardium and a transannular patch was used for enlargement of the right ventricular outflow tract followed by commissurotomy of the pulmonary valve and resection of subpulmonary discrete lesion. She was uneventful and postoperative pulsed doppler echocardiogram showed good results. PMID- 8492499 TI - [A case report of successful removal of entrapped IABP by Lambert's method]. AB - A 68-year-old man who necessitated IABP support for acute myocardial infarction suffered from IABP entrapment after its perforation. We washed intra-balloon space several times with heparinized normal saline, and finally could successfully remove it without surgery. It appears that the washing method (Lambert's method) for IABP entrapment could be done with lower risk especially for severe cases. PMID- 8492500 TI - [A case report of graft-versus-host disease caused by using stored blood after aortic valve replacement]. AB - A 61-year-old man underwent aortic valve replacement and received transfusion of 8 units of stored blood. Erythema appeared on the entire body the 12th day after operation, and was followed by high fever, elevation of liver enzymes, progressive pancytopenia, aplastic bone marrow and diarrhea. He died due to septic shock on the 19th postoperative day. Skin biopsy showed the typical features observed in graft-versus-host disease (GVHD). Based on the clinical course, skin and bone marrow biopsy, we diagnosed as post-transfusion GVHD. Therefore, even when stored blood or stored red blood cells are used, these should be irradiated and transfused through the leukocyte removal filter. PMID- 8492501 TI - [Successful repair of total anomalous pulmonary venous connection and incomplete endocardial cushion defect associated with left isomerism]. AB - Successful repair of a 8-month-old girl with polysplenia was reported. The cardiovascular anomalies were TAPVC (II b), incomplete ECD, interruption of inferior vena cava with hemiazygos continuation, bilateral superior vena cava, and left superior vena cava draining into the coronary sinus. Cardiopulmonary bypass was established with ascending aortic perfusion and caval cannulation. A left superior vena cava was directly cannulated after establishing partial bypass. In this case the left pulmonary vein drained into the right atrium near the orifice of the coronary sinus, so the atrial septal flap was made and sutured between the orifice of the left pulmonary vein and the coronary sinus in order to avoid late pulmonary vein obstruction. Then, atrium was separated by an intraatrial baffle which was sutured to the atrial septal flap. Recently, it becomes possible to surgical repair of polysplenia syndrome according to the advancements of the diagnostic methods, cardiopulmonary bypass, and the technique of the open heart surgery. PMID- 8492502 TI - [A case of constrictive pericarditis after myocardial revascularization]. AB - A case of constrictive pericarditis that occurred 4 months after CABG is reported. After undergoing CABG the patient developed pneumopericardium with a subsequent pericardial effusion, which were successfully treated with steroids and diuretics and the patient was discharged asymptomatic. About 3 months later easy fatiguability, abdominal bloating and pedal edema appeared, prompting him to undergo a thorough examination, which revealed the presence of constrictive pericarditis. At that time the graft was shown to remain patent. Eight months post CABG pericardial stripping was performed through a median sternotomy with confirmation of a fall in the CVP and PAP (diastolic) intraoperatively. Towards postoperative day 3, however, the CVP rose again with reappearance of abdominal bloating. Hence, cardiac catheterization was performed once again. The RV pressure tracing showed dip and plateau, and reoperation was performed. Pericardial stripping performed on the lateral and supradiaphragmatic sides of the left ventricle via a left anterior thoracotomy brought about a satisfactory hemodynamic improvement. PMID- 8492503 TI - [A concomitant operation of aorto-coronary bypass graft and lung cancer: report of a case]. AB - A case of a 66-year-old man with ischemic heart disease and lung cancer is reported. Chest roentgenogram revealed an irregular 2.8 x 2.0 cm mass in the right upper lobe. Coronary angiography showed 75-90% stenosis of the left anterior descending artery, and these lesions was suspected to cause perioperative myocardial infarction. A concomitant operation of aorto-coronary bypass graft and right upper lobectomy was performed through median sternotomy. A concomitant operation must be considered to be definitive and ideally preferable in selected cases. PMID- 8492504 TI - [A case report on progressive hematomatous organizing empyema accompanied with intrathoracic hemangioma]. AB - The patient, a 63-year-old woman, who had undergone extra-pleural plombage due to tuberculosis in 1961, was regularly treated for chronic empyema at our outpatient clinic since 1988. The patient who complained of difficulty in breathing because of a recent increase in empyema was admitted to our facility. On a test puncture, pure blood was aspirated without limitation, suggesting the presence of hematoma. On August 5, 1991, pleural decortification, excision of the left upper lobe and thoracoplasty were performed. Perioperative findings included repletion of hematoma and sphacelus in the lumen of thick fibrous capsule, with partial subcutaneous fenestration. Pathologically, cavernous hemangiomas were observed dispersely under the capsule. PMID- 8492505 TI - [Prostatitis and its related disorders]. PMID- 8492506 TI - [Nucleolar organizer regions in renal cell carcinoma]. AB - Argyrophilic Nucleolar Organizer Regions (AgNORs) were examined in 96 patients with renal cell carcinoma undergoing nephrectomy at Department of Urology, Chiba University Hospital during 1985-1990. Silver staining was performed with one-step method described by Ploton5), and average numbers of grains in a cell were obtained by counting 100 cells. Numbers of AgNORs were increased along with up grading. When AgNORs were compared in various cell types, the number in pleomorphic and spindle types and that in Bellini duct carcinomas were more than that in common types. The number of AgNORs correlated with pT and pV factors, but no relationship was shown between the number and these factors when compared in the same grade. The tumor size correlated with the number of AgNORs. The number of AgNORs in the primary legion showed a reversed correlation with doubling times calculated from either primary, recurrent or metastatic legions examined in 22 cases. In all cases it tended that the number of AgNORs correlated with survival, however survival in G3 cases was not influenced due to worse prognosis. It was concluded that the number of AgNORs in renal cell carcinoma was an additional factor for estimating the properties of tumor cells. PMID- 8492508 TI - [Long-term results and risk factors of tumor recurrence in patients with superficial bladder cancer who were treated by intravesical bacillus Calmette Guerin (BCG) instillation]. AB - An evaluation was made of the long-term results and risk factors of tumor recurrence in patients with superficial bladder cancer who were treated with intravesical bacillus Calmette-Guerin (BCG) and who had a mean follow-up period of 57 months. Eligible for the study were a total of 102 patients who were treated by transurethral resection of tumors and were considered to be free from tumor from 1984 to 1989. A suspension containing 80 mg Tokyo 172 strain BCG in 50 ml normal saline was given intravesically to 50 patients once a week for six weeks without further maintenance instillation. To the other 52 patients was additionally given monthly intravesical BCG instillation for 12 months. The actuarial nonrecurrent rates according to sex, different BCG treatment protocol, tumor grade, tumor status including primary or recurrent tumors, and solitary or multiple tumors were estimated by Kaplan-Meier method. The estimated three-, five and seven-year actuarial nonrecurrent rates in all 102 cases were 77.3%, 68.5% and 60.6%, respectively. When nonrecurrent rates were compared to tumor characteristics, no statistically significant differences were observed between primary and recurrent tumors or between solitary and multiple tumors estimated by generalized Wilcoxon method. On the other hand, when nonrecurrent rates were compared with tumor grades, grade 3 tumor showed a 40.0% three-year nonrecurrent rate. The differences between grade 3 and grade 1 and between grade 3 and grade 2 were statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492507 TI - [Characterization of primary and metastatic cell lines established from a patient with renal cell carcinoma]. AB - We established four renal cell carcinoma (RCC) cell lines (HANKS), namely the primary tumor (HANKS-Pr), metastasized to the lung (HANKS-Lu), liver (HANKS-Li) and lymph node (HANKS-LN) derived from a patient with advanced RCC, and analyzed their characters. Each had an epithelial morphology and exhibited multilayering. These cell lines have been maintained for more than 36 months and over 100 in vitro passages. In karyotype analysis, the common aberration in the four cell lines was marker chromosome t (3;18) (p13;q21). In soft agar culture, HANKS-Pr showed the lowest growth. Furthermore, we found high level expression of major histocompatibility complex (MHC) class I antigen on HANKS-Pr and HANKS-Lu, and low expression of MHC class II antigen on four cell lines. HANKS-LN had transplantability in nude mice. We determined the different biological properties among HANKS cell lines stemming from the same origin. PMID- 8492509 TI - [An experimental study of PAH clearance in chronic unilateral and completely obstructed kidney]. AB - The following experiment was performed to estimate PAH clearance of chronic unilateral and completely obstructed kidney and to explore its change during obstruction period. Thirty adult male mongrel dogs were used. Unilateral complete ureteral obstruction was made by ligation of the left ureter proximal to the bladder. After 3, 5, 10, 20 and 40 days of obstruction, an experiment was performed. Under laparotomy, the left kidney was exposed and polyethylene catheter was inserted into the renal pelvis. Intrapelvic pressure was monitored by pressure transducer. In a condition that PAH (p-aminohippurate) was constantly infused intravenously, intrapelvic urine of the obstructed kidney was exchanged for physiological saline. After the exchange, intrapelvic PAH concentration was measured at hourly intervals for 4 hours. At each midpoint of the measurements, plasma PAH concentration was measured. At the end of the experiment, the obstructed kidney was resected and pelvic capacity was measured. PAH of the obstructed pelvis increased at hourly intervals after the exchange. The result showed that the clearance ability was maintained in the completely obstructed kidney. PAH clearance values were 16.3, 13.6, 1.0, 0.9, 0.9 ml/hr/kg b.w. at 3, 5, 10, 20 and 40 days obstruction respectively. PAH clearance decreased sharply during early stage of obstruction and tended to reach a fixed low value at over 10 days of obstruction. Our experimental method seemed to be available to estimate the clearance ability of chronically, unilaterally and completely obstructed kidney. PMID- 8492510 TI - [Lymphadenectomy in the operative treatment of renal pelvic and ureteral carcinoma]. AB - We evaluated 18 patients with renal pelvic and ureteral carcinoma focusing on the operative treatment. All the patients underwent nephroureterectomy and partial cystectomy, except for two patients, with CIS of the ureter and renal insufficiency, and one with invasive bladder carcinoma, in whom partial ureterectomy and total cystectomy were performed, respectively. Lymphadenectomy were performed in all the patients and resected lymph nodes were from renal hilus, para-aorta or vena cava, according to the affected side, intra aorto-caval and all the pelvic nodes in the affected side. Lymph node metastases were found in 4 patients (22%), 2 in the primary and distant nodes and the other in the regional nodes only. Skipped lesion of the lymph node metastasis was not rare and lymph node dissection from the renal hilus to the pelvis on the affected side should be included in the operative treatment of renal and ureteral carcinoma. PMID- 8492511 TI - [The effect of long-term alkali therapy for recurrent calcium stone patients with distal renal tubular acidosis]. AB - Alkali therapy is widely accepted as a treatment for recurrent calcium stone patients with distal renal tubular acidosis (dRTA). Nine patients, five with complete and four with incomplete type of dRTA, were treated with alkali agents for more than three years; an average period of 10.8 years. In five patients, new stone formation and stone growth were completely prevented by this treatment. Among the four failed cases, three did not take enough alkali agents (in spite of our medication), and the other had recurrent urinary tract infection resulting in infectious stone formation. In conclusion, the long-term efficacy of alkali therapy for prevention of recurrent stone formation with dRTA is confirmed when the patient takes enough alkali agents and the urinary tract infection is well controlled. PMID- 8492512 TI - [Clinical results in the treatment for primary carcinoma of the renal pelvis and ureter]. AB - One hundred and five patients with renal pelvic and ureteral tumor entered our treatment program between 1982 and 1991. Of 105 patients, 81 had resectable transitional cell carcinoma and were treated with radical or total nephroureterectomy (57 vs. 24) and/or lymph node dissection (66). Adjuvant chemotherapy was added in 26 patients with high stage disease and with lymph node disease. There were 61 male and 20 female patients. Their ages ranged from 36 to 86 years, with a mean of 62 years. The follow-up period was 3 to 114 months, with a mean of 31 months. The estimated 5-year survival was 67% in all 81 patients. Classified according to the pathological stage, 5-year survival was 70% in pTis + pTa disease group, 91% in pT1 group, 88% in pT2 group, 53% in pT3 group, and 27% in pT4 group. Under the grading system, 5-year survival was 100% in grade 1 disease, 74% in grade 2, and 26% in grade 3. It was 78% in 52 patients with negative node disease and 26% in 15 with positive node disease. There were 51 patients (61%) with no recurrent disease. Seventeen patients (21%) had recurrence in the bladder after a median latent period of 8-month, and 15 (19%) patients had recurrence in the retroperitoneum, liver, lung and (or) other site after a median latent period of 8 months. The results of this series were quite similar to those of previous reports. The efficacy of lymph node dissection and adjuvant chemotherapy could not be confirmed. PMID- 8492513 TI - [A questionnaire survey on urinary incontinence in geriatric nursing home patients]. AB - A survey by questionnaires was performed to understand the present conditions of urinary incontinence in the aged. The objects were 748 persons who were residing in eight geriatric nursing homes locating in Nara Prefecture. The answers from 183 males and 565 females ranging from 57 to 101 years old were collected and analyzed. The answers were interpreted as follows: (1) Of these 748 persons 422 (56%) were incontinent, 94 males (51%) and 330 females (58%). (2) The higher age group tends to show the higher rate of incontinence. (3) The rate of incontinence seems to highly correlate with the degree of dementia and impaired mobility. (4) Sixty-nine persons (16%) had consulted a nursing home doctor and/or other medical doctors, only 20 of whom had been medicated for incontinence. (5) An institution where a behavioral therapy program had been employed showed a lower rate of incontinent persons. From these results, it is considered that not only an increase of nursing staff but also aggressive participation of medical specialists including urologists are needed to improve their quality of life. PMID- 8492514 TI - [Urinary hCG beta-core fragment as a tumor marker for bladder cancer]. AB - Human chorionic gonadotropin (hCG) is a highly specific tumor marker or trophoblastic neoplasms. Also in patients with non-trophoblastic tumors, hCG beta related material has been frequently demonstrated in their urine. This material was termed beta-core fragment (beta-CF) since it is recognized by hCG beta-core directed antisera but not by hCG beta-carboxyterminal peptide (CTP) directed antisera. We measured the concentration of beta-CF in the urinary samples from patients with urothelial tumors and studied its clinical usefulness as a tumor marker. The concentration of beta-CF was expressed as ng/mg of creatinine in the urine and the cut-off value was 0.1 ng/mg.Cr. Thirty (61.2%) of 49 patients with bladder carcinoma had raised beta-CF levels and the positive rates were dependent upon pathological grade (25.0, 33.3 and 82.8% at G1, G2 and G3, respectively). The elevated urinary beta-CF were also detected in 5 of 7 patients with upper urinary tract carcinoma. However, there was no elevated urinary beta-CF level in prostate carcinoma. Serial determination in 13 patients with elevated beta-CF level prior to therapy showed that 12 patients had decreased concentrations after successful treatment, but 1 patient with persistently elevated urinary beta-CF level after treatment subsequently relapsed. The determination of urinary beta-CF may provide a useful tool in identifying and monitoring the response to treatment in patients with carcinomas of the bladder and the upper urinary tract. PMID- 8492515 TI - [Use of Nd:YAG laser and flexible cystoscope in outpatient treatment of recurrent superficial bladder tumors]. AB - Nd:YAG laser irradiation and flexible cystoscopy were used in the outpatient management of 16 cases (21 sessions) with superficial bladder tumors. Irradiation of tumors was accomplished in all cases except 3 in which the visual field was affected by bleeding after the cup biopsy of tumors. Tumors at the bladder neck were easily irradiated through the flexible cystoscope. No tumor recurred at or near the previously irradiated site. This method provided a safe and cost effective means to treat superficial bladder tumors in selected cases. PMID- 8492516 TI - [Early changes of sugar chains in bladder luminal cell membrane of rat treated with N-butyl-N-(4-hydroxybutyl) nitrosamine detected by immunohistochemical transmission electron microscopy]. AB - Early changes of sugar chain detected by binding with lectins on luminal cell membrane of rat bladder epithelium treated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were immunohistochemically examined with a transmission electron microscopy using ferritin-labeling lectins. BBN was given to male Wistar rats at the concentration of 0.05 W/V% in drinking water, and the rats were sacrificed at 4, 8, 16, 20 weeks, respectively, after the beginning of the BBN treatment. The bladder was treated with Half Karnovsky's solution via intra aortic cannulation for 20 minutes, and then removed. A part of bladder was examined grossly and by a light microscopy. The other part was cut into 3 x 3 mm squares and fixed with 2.5% glutaraldehyde solution and washed with 0.1 M cacogyl buffer with 10% sucrose. The tissue was sectioned and then incubated with ferritin-labeling lectins; concanavalin A (Con A), ulex europeaus agglutinin (UEA 1), peanut agglutinin (PNA) and dolichos biflorus agglutinin (OBA), respectively. These specimens were examined under a transmission electron microscopy. In cell membrane of the normal bladder, binding of Con A was found occasionally and binding of PNA was found focally, but binding of UEA-1 and DBA occurred incompletely on the cell membrane. The plaque and ridge on cell surface of bladder epithelium found to be obscured at 8 weeks after the treatment with BBN, and microvilli were barely observed under an electron microscope, but they increased gradually and could be seen by the microscope at the time of 16 weeks after the BBN treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492517 TI - [Mechanisms of relaxing action of papaverine on isolated canine corpus cavernosum]. AB - The mechanisms of relaxing effect of papaverine on the phenylephrine (10(-6) M)- or the high K+ (30 mM)-induced contracture were studied on the isolated canine corpus cavernosum. Rod shaped preparation of the corpus cavernosum without the tunica albuginea was mounted in a tissue bath, immersed in Tyrode solution and the isometric tension was recorded. Cumulative applications of papaverine (10(-6) approximately 3 x 10(-5) M) relaxed the phenylephrine (10(-6) M)- or the high K+ (30 mM)-induced contracture with a dose-dependent manner. A pretreatment with papaverine (10(-5) approximately 10(-4) M) dose-dependently reduced the magnitude of the phenylephrine (10(-6) M)-induced contracture, more prominently in the tonic than in the phasic component, while reduced that of the high K+ (30 mM) induced contracture in both components. The relaxing effect of papaverine (5 x 10(-6) M) on the high K+ (30 mM)-induced contracture was antagonized by an increase in extracellular Ca++ concentration. A reintroduction of Ca++ after perfusion of Ca++ free and high K+ (30 mM) solution containing 1 mM EGTA failed to bring about normal contractile activity in the presence of papaverine (10(-4) M), Papaverine, even if its high concentration (10(-4) M), could not completely abolish the transient phasic contraction evoked norepinephrine (10(-5) M) which was abolished by ryanodine (3 x 10(-6) M), in Ca++ free solution. Isoproterenol (10(-8) approximately 10(-6) M) or dibutyryl cyclic-AMP (10(-5) approximately 10( 3) M) relaxed the phenylephrine (10(-6) M)- and the high K+ (30 mM)-induced contracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492518 TI - [The effect of unilateral ureteral obstruction on the contralateral renal growth in weanling rats]. AB - The effect of unilateral hydronephrosis on the growth of contralateral kidney were evaluated with weanling rats of which kidneys were in growing stage (body weighted between 80 g and 90 g). These rats underwent complete unilateral ureteral obstruction (CUUO) on day 0. They were divided into 3 groups and went through second operations on day 3 (CUUO-3) as follows; a) CUUO released, b) nephrectomy performed and c) CUUO continued. Sham-operation was performed on day 0 and on day 3 to the controls. Wet weights and bromodeoxy-uridine (BrdU) labeling index (L.I.) (index for cell proliferation in the uriniferous tubules) of the contralateral kidneys were measured for the evaluation. The wet weights were significantly higher in all the groups than that of the controls throughout the observation period on and after the day 3. The group that underwent nephrectomy demonstrated a sharp rise in L.I. after the day 7. In the group that was continued in CUUO, the L.I. started to rise later than its rise in nephrectomised group but the index caught up at the time when the blood flow completely disappeared in the kidneys of the ligated side. L.I. in the group of which CUUO was released became significantly higher than that of controls on the day 7 and remained its significance until the day 21 in spite of resolution of the hydronephrosis. To reveal the effect of length of obstructed term, the same trial was carried out that rats endured in CUUO for 5 days (CUUO-5) till the second operation. This turned out lower L.I. in the CUUO-5 than the CUUO-3. These results suggest that the presence of hydronephrosis made by CUUO suppress the growth (cell proliferation) of contralateral kidney and also duration of obstruction can be critical on the renal growth that shorter obstructed period turns out preferable for cell proliferation after relief of CUUO. PMID- 8492519 TI - [Evaluation of prognostic factors in patients with stage 1 renal cell carcinoma]. AB - During the past thirty-five years, we treated 221 patients with stage 1 renal cell carcinoma. We classified these patients into two groups: 175 patients who did not show recurrence and 45 patients who showed recurrence (excluding one patient who died of other disease). We investigated factors which affect the recurrence after nephrectomy and the survival after recurrence in these two groups. We found two major factors such as tumor diameter and tumor grade which affected the recurrence of renal cell carcinoma. Of these two factors, the grade of malignancy affected the prognosis of the patients with stage 1. Furthermore, as a result of long-term observation, we found that patients with grade I showed good prognosis compared with these with grade II, III and IV. The patients who showed weight loss constituted the majority of recurrent patients. Anaemia, erythrocyte sedimentation rate and positive reaction of C-reactive protein in addition to weight loss were major factors affecting the prognosis of stage 1 patients. In an effort to analysing the features of recurrent patients, there observed that no significant difference of the non-recurrent rate was detected between the patients who showed cancer death after nephrectomy and the patients who were living after nephrectomy. In analysing metastatic lesions and numbers of metastatic foci, we detected relatively long-term survival especially in patients with less than 3 foci of metastases in the lung, compared to those with multiple foci. Furthermore, we found dimension of the metastasis depended on the grade of the primary lesion. PMID- 8492521 TI - Progress report. PMID- 8492520 TI - [A case report of pseudolymphoma of the kidney and orbit]. AB - Pseudolymphoma is reactive extranodal lymphocytosis, and it's lymphocytes are so minimally atypical that it is basically benign. The patient was a 68-year-old female with pain in the left back and lower abdomen. Plain CT (computerized tomogram) of the kidney revealed a mass in the left kidney. It had a smooth surface and higher density than parenchyma. Similarly a left orbital mass was revealed by CT. We could not deny the mass to be a malignant tumor, so we took specimens from these lesions by an open biopsy. Histological examination of these specimens showed pseudolymphoma. Pseudolymphoma of the left kidney was reduced in its size by treatment with prednisolone. The patient is continuously followed up to date. PMID- 8492522 TI - Spoliation of evidence: a developing tort. PMID- 8492523 TI - Ring-enhancing lesions on CT scan and blindness in an AIDS patient. PMID- 8492524 TI - The epidemiology of HIV/AIDS in Kansas. PMID- 8492525 TI - Knowledge and attitudes about HIV/AIDS among Kansans. PMID- 8492526 TI - Public health services for HIV/AIDS patients in Kansas. PMID- 8492527 TI - Coping with AIDS: a cognitive therapy perspective. PMID- 8492528 TI - Screening for breast cancer: Kansas, 1992. PMID- 8492529 TI - Aggressive heparin therapy for DVT. PMID- 8492530 TI - Gender differences: implications for understanding women's development. PMID- 8492531 TI - Nurse is not gender specific. PMID- 8492532 TI - The male nursing students: implications for nurse educators. PMID- 8492533 TI - Operation immunize. A nursing opportunity: its success is up to you. PMID- 8492534 TI - Kansas risk management laws and nursing practice: approaches towards compliance in reporting substandard nursing practice in acute care facilities. AB - This article provides a structural outline of the many basic elements needing to be considered when institutions are developing a system for review of incidents that may fall below the applicable standard of care. Details for program development need to be explored and implemented with the mindset that the process will be modified and continuously improved over time. Protecting the interest of the individual licensee, the healthcare institution and the public are important aspects that demand attention when complying with the Kansas Risk Management Laws as they pertain to nursing practice. PMID- 8492535 TI - [Possible character of a professional academy]. PMID- 8492536 TI - [Counseling for nurses. Starting a career the wholesome way]. PMID- 8492538 TI - [4 women, 4 careers]. PMID- 8492537 TI - [Job hunting during unemployment]. PMID- 8492539 TI - [Successful realization of the SRK rules for nursing education. Into the future with diploma I]. PMID- 8492540 TI - [Educational rules of the SRK. Who should do what?]. PMID- 8492541 TI - [Swiss Nursing Association for official recognition]. PMID- 8492542 TI - [Experiencing body and illness. "I can no longer do as I please"]. PMID- 8492544 TI - [To chose one's way]. PMID- 8492543 TI - [My work place. An unusual emergency case]. PMID- 8492545 TI - [And if we talked about "career"?]. PMID- 8492546 TI - [Making a career in nursing care?]. PMID- 8492547 TI - [Higher studies in nursing. Everyone can plan in his own way]. PMID- 8492549 TI - [The happy feeling of success]. PMID- 8492548 TI - [The importance of nutrition for the elderly patient. Eating well--at the hospital]. PMID- 8492550 TI - [Use of electrography. How to establish bioenergetic relationships]. PMID- 8492551 TI - [What is an "expert in nursing care"?]. PMID- 8492552 TI - [Career planning in nursing]. PMID- 8492553 TI - [A study of the cantonal hospital in Basilea. Standards of quality of geriatric care]. PMID- 8492554 TI - Evaluation of the West Australian School Development in Health Education Project. AB - In December 1990, the National Centre for Research into the Prevention of Drug Abuse was invited to evaluate the School Development in Health Education Project (SDHE), a national program tested in Western Australia (WA) in 1991. A formative evaluation indicated the project was moderately successful in achieving the objectives in the operational plan. Schools involved reported the project was successful, and they agreed to continue health planning meetings during 1992. The evaluation also indicated that while most schools achieved macro-level change, they achieved little at the micro level. A significant outcome for SDHE WA was the successful application for three-year funding to continue and expand the project as the West Australian School Health program (WASH). Recommendations generated from the SDHE evaluation produced a shift in emphasis for the WASH program from the "action research" orientation of the national program to more content-based professional development. This study highlights the important role formative evaluation can play in developing and refining health education programs. PMID- 8492555 TI - Perceived health needs of secondary school students in Uyo, Akwa Ibom State, Nigeria. AB - Nigeria generally has overlooked the health needs of its adolescents. To determine student perceptions of their health-related needs, some 600 students in Uyo, the capital of Akwa Ibom State, were surveyed, and they identified several concerns. Their responses provided the basis to offer five recommendations for action: improve the quality of school health service facilities and personnel available in the secondary schools; implement a comprehensive national program of drug education and control; provide a healthful school environment; assess the quality and quantity of food provided to students, especially in boarding schools; and implement a comprehensive school health education program in Nigerian schools. PMID- 8492556 TI - Ten unanswered questions regarding comprehensive school health promotion. AB - The past two decades witnessed dramatic growth in support for comprehensive school health promotion. Yet, many questions about its effectiveness and feasibility remain unanswered. This article poses several research and policy questions, the answers to which may help to shape the future of school health programs in this country. PMID- 8492557 TI - Relationships between expectancies and adolescent dieting behaviors. AB - Dieting expectancies are cognitive variables pertaining to anticipated outcomes individuals expect to obtain from dieting to lose weight. This investigation examined the factor structure of dieting expectancies in an adolescent population, age 10-18, and tested the ability of factors to distinguish among types of dieter, diet pill user, and vomiter groups. Emerging from a principal components analysis were five reliable expectancy factors: Social Confidence, Social Approval, Self-Worth, Positive Performance, and Negative Consequences. Results indicate dieting expectancies and gender are important in distinguishing among adolescents who engage in different dieting practices. Gender and Self Worth were particularly important in distinguishing frequent dieters from nondieters. Social Approval was best at separating frequent dieters from occasional dieters, diet pills users from nonusers, and vomiters from nonvomiters. PMID- 8492558 TI - Reactions among Dutch youth toward people with AIDS. AB - AIDS education emphasizing personal responsibility toward AIDS-inducing behavior might enhance negative reactions to people with AIDS. This study, based on Weiner's attributional theory of motivation and emotion, addressed this dilemma by reporting data from a sample of 1,018 Dutch secondary school students. Results support the reasoning that emphasizing personal responsibility, and consequently personal controllability, increases negative reactions to people with AIDS. In addition to causal attributions, however, AIDS knowledge and attitudes toward homosexuality also related significantly to reactions to people with AIDS. To prevent negative reactions to people with AIDS, the subject of homosexuality should be dealt with before AIDS education is provided. AIDS education should address the impossibility of HIV infection by daily interactions, and the meaning and consequences of being seropositive. PMID- 8492559 TI - How volunteer health professionals brought medical care to Pasadena's uninsured children. PMID- 8492560 TI - The Edina, Minnesota, school crisis response team. PMID- 8492561 TI - Comparative studies on the detection of benzodiazepines in serum by means of immunoassays (FPIA). AB - Serum was tested for benzodiazepines by fluorescence polarization immunoassay (FPIA) on Abbott's ADx system using the benzodiazepine serum reagents (Benzo S) and the benzodiazepine urine reagents (Benzo U) after pretreatment of specimens by means of acetone precipitation. The following sera were included for comparing the two methods: negative sera spiked with various benzodiazepines; 80 sera randomly selected out of a total of 8654 serum specimens from impaired drivers; and blood specimens from individuals who stated that they had taken benzodiazepines. The different benzodiazepines were added to serum at concentrations of 25, 75, and 300 ng/mL. The low-dose benzodiazepines flunitrazepam and triazolam were additionally tested at serum concentrations of 10 ng/mL. Because of the better reproducibility and the shift of the dynamic range to lower concentrations, the Benzo S assay was found to be more sensitive than the Benzo U assay after acetone precipitation. The direct ADx benzodiazepine serum assay has clear advantages over the acetone precipitation method, especially with regard to therapeutic concentrations and for the detection of the highly potent and low-dose benzodiazepines flunitrazepam and triazolam. PMID- 8492562 TI - Rapid toxicological screening of barbiturates in plasma by wide-bore capillary gas chromatography and nitrogen-phosphorus detection. AB - A rapid screening technique for the identification and quantitation of some barbiturates in plasma is reported. The method employs a one-step extraction at pH 5.8 into an organic phase, separation of compounds by gas chromatography with a wide-bore (0.75-mm i.d.) fused-silica capillary column connected to a direct injection kit, and nitrogen-phosphorus detection. Identification of each barbiturate is by retention time relative to brallobarbital, confirmed using another wide-bore column of slightly different polarity, connected to a flame ionization detector. Rapid quantitation may be obtained with extracted standards used for drug screening. Detection threshold (0.5 micrograms/mL in a 0.5-mL serum sample and 0.5-microL injection volume), precision (CV < or = 11%), and linearity (r > 0.99) were satisfactory for routine toxicological applications. PMID- 8492563 TI - GC/MS analysis of five common benzodiazepine metabolites in urine as tert-butyl dimethylsilyl derivatives. AB - A method for the GC/MS confirmation of oxazepam, nordiazepam, desalkylflurazepam, temazepam, and alpha-hydroxyalprazolam in urine is described. The method incorporates a solid phase extraction technique developed by Varian which was found to extract all five metabolites with recoveries exceeding 73%. The extracted metabolites were derivatized with N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA), resulting in the formation of stable tert butyldimethylsilyl (TBDMS) derivatives. Quantitation was performed by GC/MS using oxazepam-D5, nordiazepam-D5, and alpha-hydroxyalprazolam-D5 as internal standards. The method was found to be linear over the range of 50-2000 ng/mL. Within-run precision, measured as the coefficient of variation at 100 ng/mL, was less than 3% for all analytes except temazepam which was 6% (N = 20). PMID- 8492564 TI - Identification of laudanosine, an atracurium metabolite, following a fatal drug related shooting. AB - In a case involving a fatal shooting, toxicology tests on blood and urine demonstrated the presence of cocaine metabolites and a large amount of an unidentified compound. This compound was subsequently identified by mass spectral, gas chromatographic, and thin layer chromatographic tests as laudanosine, a metabolite of the skeletal muscle relaxant atracurium which was administered during emergency surgery. Identification was confirmed by comparison with commercially available standards. Because of the difficulty associated with isolating and chromatographing highly water-soluble compounds, recognition of this artifact is a useful tool in identifying these cases. PMID- 8492565 TI - Breath-alcohol analysis and its independence of atmospheric pressure: a general proof. PMID- 8492566 TI - Distribution of morphine in body fluids of heroin users. PMID- 8492567 TI - Detection of acetonitrile and other polar solvents by capillary gas chromatography after direct injection of deproteinized serum. PMID- 8492568 TI - Determination of amphetamine and methamphetamine in blood by derivatization with perfluorooctanoyl chloride and gas chromatography/mass spectrometry. AB - A relatively simple method for quantitation of amphetamine and methamphetamine in blood was developed. Blood samples were extracted with cyclohexane, and the extracts were derivatized with perfluorooctanoyl chloride prior to gas chromatography/mass spectrometry. Selected ions were monitored at m/z 118 and 440 for amphetamine, m/z 118 and 454 for methamphetamine, and m/z 121 and 443 for the internal standard amphetamine-d3. The imprecision was less than 5% for amphetamine and less than 9% for methamphetamine. Limits of detection were 11 micrograms/L for amphetamine and 13 micrograms/L for methamphetamine, while limits of quantitation were 22 and 34 micrograms/L, respectively. Calibration curves were linear in the ranges 14-2700 micrograms/L and 15-3000 micrograms/L, respectively. Some drugs that were known or suspected to interfere with immunological or chromatographic methods for amphetamine and methamphetamine were tested for interference. None of the drugs tested interfered, except for a substance in putrefied blood samples, which was found to interfere with one ion (m/z 118) for amphetamine but not with the second ion. PMID- 8492569 TI - Antibody-mediated interference of a homogeneous immunoassay. AB - We hypothesized that an antibody-mediated interference could arise in a homogeneous immunoassay used to determine the presence of cocaine metabolites in urine. Urine specimens containing benzoylecgonine (BE) at concentrations near the National Institute on Drug Abuse (NIDA) threshold were assayed in replicate determinations by EMIT. Excess reagent protein (containing antibody specific for cocaine metabolites) was added to specimens to test for an antibody-mediated interference. Replicates of the BE-fortified specimens tested by EMIT that did not contain excess reagent antibody were all positive by the assay, while those that contained the excess reagent antibody were all negative. Because it may be difficult to detect excess interfering antibody by using some traditional tests for urine adulteration, we present these findings to illustrate a potential problem for some homogeneous immunoassays in forensic urine drug testing programs. PMID- 8492570 TI - Solid phase extraction and HPLC analysis of toxic components eluted from methyl methacrylate dental materials. AB - Methyl methacrylate polymer (PolyMMA) is widely used as the composite resin for the dental plate. During the fabrication process of PolyMMA for the polymerization reaction, benzoylperoxide (BPO) and N,N-dimethyl p-toluidine (DMPT) are added as the initiator and the stimulator, respectively. Because these compounds exhibit toxicity as well as a residue potential, their use raises concerns regarding human safety. The degree of dissolution into serum was determined to evaluate risk to the user. Analysis was by HPLC combined with solid phase extraction using a C-18 column. The eluted compounds were found to be in the order of 10 to 100 ppm. PMID- 8492571 TI - Serial plasma concentrations of cocaethylene, cocaine, and ethanol in trauma victims. AB - Cocaethylene (EC), cocaine (COC), and ethanol (ETOH) concentrations were measured in 46 serial plasma samples from 15 male trauma victims. In all but two patients EC was detected on admission to the hospital. In the remaining two, EC was not detected throughout hospitalization. However, these two patients had the lowest ETOH concentrations in the series (200 and 300 mg/L). Plasma concentrations ranged up to 128 micrograms/L for EC, up to 421 micrograms/L for COC, and up to 5,100 mg/L for ETOH. Ratios of EC to COC concentration (EC/COC) were as high as 4.1. Concentrations of EC showed statistically significant correlation with those of COC (p < 0.01). The plasma half-life (T1/2) of EC was found to be longer than that reported for COC (1 h) and was estimated to be 3.5, 4.5, and 5.5 h in three patients. PMID- 8492572 TI - Measurement of benzoylecgonine in whole blood using the Abbott ADx analyzer. AB - An alternate procedure has been developed for the processing of whole blood for the estimation of benzoylecgonine with the use of the Abbott ADx reagents and analyzer. This procedure allows for handling of relatively large numbers of samples without the need to evaporate extraction solvent. Blood samples were diluted with an equal volume of phosphate buffer-methanol (80:20 v/v), and the proteins were removed by centrifugation through a membrane filter device. A comparison of the proposed method with an acetone solvent extraction procedure has been made, and results were shown to be equivalent. Recoveries of 94-105% benzoylecgonine were obtained for added concentrations of 25-500 ng/mL. PMID- 8492573 TI - Selective determination of inorganic mercury and methylmercury in tissues by continuous flow and cold vapor atomic absorption spectrometry. AB - A method has been developed for the determination of inorganic (InHg) and methylmercury (MeHg) in solubilized tissues with continuous-flow (flow injection) cold vapor atomic absorption spectrometry. Kidney, liver, and brain tissues were spiked with MeHg and InHg and solubilized at an elevated temperature in a solution containing 90 g/L NaOH, 2 g/L L-cysteine, and 4 g/L NaCl. Total mercury determination was achieved by continuous-flow cold vapor atomic absorption spectrometry using an inlet system containing a flow through photo-oxidation reactor and sodium borohydride as the mercury reductant. InHg was selectively determined in the presence of MeHg with this method when using stannous chloride as the reductant. MeHg concentrations were computed as the difference between the values obtained from the two analyses. Recoveries for spiked tissues were above 95% for InHg and MeHg. Quantitation limits for InHg and total mercury in tissues were 0.4 and 0.6 microgram/g, respectively. MeHg chloride levels from kidney tissues of exposed rats were evaluated using the present method in comparison with another method in which MeHg was measured using solvent extraction and capillary gas chromatography with electron capture detection. PMID- 8492574 TI - The use of bone marrow in the study of postmortem redistribution of nortriptyline. AB - Thirty-two New Zealand Albino rabbits (1.5-2.0 kg) were dosed on a daily basis with 20 mg/kg nortriptyline (NT) prior to feeding for a period of five days. On the fifth day of dosing, the animals were sacrificed approximately 1.5 h after the final dose. A comparison was made of nortriptyline concentrations in the blood and bone marrow at the time of sacrifice, and between bone marrow collected at the time of sacrifice and bone marrow collected at 2, 4, 6, 12, 24, 36, and 48 h after sacrifice. The results indicate that a linear relationship exists between blood and bone marrow NT concentrations, with an average marrow-to-blood ratio of 29.98 +/- 3.91 and a correlation coefficient of 0.956. Additionally, there was no significant difference (p > 0.05) observed between NT concentrations in bone marrow at the time of sacrifice and its concentration up to 24 h after sacrifice. The results indicate that bone marrow may be used to predict blood concentrations of NT up to 24 h after death when a suitable blood sample is not available. PMID- 8492575 TI - Role of serum markers for liver function and liver regeneration in the management of chloroform poisoning. AB - Accidental or intentional chloroform poisoning is rare, but a few such cases have been reported in literature. We report here a successful management of acute chloroform toxicity in a 33-year-old white female who attempted suicide by injecting one half milliliter of chloroform, followed by drinking half a cup the next morning. Plasma chloroform levels, measured by headspace gas chromatography declined rapidly. Sequential measurement of biomarkers in serum for liver cell necrosis, liver function, and liver regeneration indicated the presence of initial liver damage followed by recovery. These results suggest that in addition to biomarkers for liver cell necrosis, serial determinations of markers for liver regeneration provide objective evidence for recovery from chloroform poisoning and possibly other hepatotoxins. PMID- 8492576 TI - Health care reform in Kentucky. PMID- 8492577 TI - American Nurses Association position statement on foregoing artificial nutrition and hydration. PMID- 8492578 TI - American Nurses Association position statement on nursing care and do-not resuscitate decisions. PMID- 8492579 TI - Staff nurse involvement in nursing research. PMID- 8492580 TI - Tasks in statistical inference for studying variation in medicine. AB - When studying variation in medicine, traditional hypothesis-testing procedures are too limited to obtain useful inferences except in special situations. More generally, full probability modelling is necessary. Even a relatively simple example can illustrate this point rather dramatically. The development and application of full-probability methods for medical problems comprise exciting areas for statistical and medical researchers, especially if working together. PMID- 8492581 TI - Estimating physician costliness. An empirical Bayes approach. AB - Outpatient data obtained from the general medicine practice of an urban, health care facility are used to provide an application of empirical Bayes techniques in the estimation of physician "costliness." The results illustrate that application of the simplest empirical Bayes estimation procedure can provide more reasonable estimates of physician's utilization of resources than a standard estimation procedure. Empirical Bayes estimates are shown to adjust for potential instability in standard estimates that may arise from either a physician treating a small number of patients or an inappropriate case-mix adjustment. Using simulation, it is demonstrated that the empirical Bayes procedure can provide overall better estimates using fewer data than the standard procedure. This application, although somewhat limited in scope, should provide impetus for increased utilization of the numerous Bayesian and empirical Bayes techniques that currently exist in the statistical literature and pertain to small area estimation techniques. PMID- 8492582 TI - Socioeconomic influence on small area hospital utilization. AB - Health care policy makers, concerned with the rising cost of health care, have focused on the observed variation in the use of hospitals as a potential area in which to lower health care costs, i.e., if hospital utilization can be decreased, health care costs may also decline. However, it is crucial that the reasons for the observed variation in the current practice be understood or attempts to reduce costs may lead to policies that harm groups of patients and the providers and institutions currently delivering care. Using hospital discharge data from 59 hospital market communities in the lower peninsula of Michigan in 1984-86, the authors examined possible associations between socioeconomic characteristics and the observed small area variation in hospital discharge rates. First, a series of Poisson regressions was used for each of five covariates and 112 modified diagnosis-related groups (DRGs). Then, multiple regressions were examined, utilizing the five socioeconomic characteristics, after excluding statistically influential communities. The results indicate that community characteristics, including education, poverty, and unemployment, have a statistically significant association with the observed small area hospital discharge rate for many DRGs. Moreover, the direction of the effect is consistent across multiple disease categories. In multiple regressions, the five selected socioeconomic variables explained 48% of the variance for medical admissions and 19% for surgical admissions. For most DRGs, high educational levels were associated with lower hospitalization rates. The authors also identified statistically influential communities whose hospital utilization profile was different from that of most communities in Michigan. PMID- 8492583 TI - Fourth Biennial Regenstrief Conference. Methods of comparing patterns of care, October 27-29, 1991. PMID- 8492584 TI - Explaining geographic variations. The enthusiasm hypothesis. AB - The causes of geographic variations in the use of health care services continue to puzzle researchers. Some have proposed that physicians in geographic areas with high rates of use provide proportionally more unnecessary care than those in other areas. Available research does not support this hypothesis. Others contend that uncertainty about the effectiveness of health services leads physicians to differing conclusions about when to perform various services and is the primary cause of geographic variations. Available research also does not support this hypothesis. This article proposes a different explanation, i.e., the enthusiasm hypothesis. Currently, research data suggest that geographic differences in the use of health care services are caused by differences in the prevalence of physicians who are enthusiasts for particular services. This analysis explores the validity of the enthusiasm hypothesis using previously published data on carotid endarterectomy. PMID- 8492585 TI - Small area variation analysis. Methods for comparing several diagnosis-related groups. AB - In small-area variation analysis, the variation of health care utilization rates, e.g., admission rates, among small areas is calculated. Frequently, the variation of one diagnosis, diagnosis-related group (DRG), or procedure is compared with the variation of another. Unfortunately, the methods generally used to make these comparisons are not consistent. They differ on whether they 1) adjust for the prevalence of the DRGs, 2) distinguish between variation among areas and variation within areas, 3) weight all areas equally, and 4) adjust for multiple admissions per person. None has an associated confidence interval. These discrepancies occur in part because there is no statistical model of small area variation. Without such a model, it is not known how to measure variation, and thus, it is not known how to compare different DRGs. Here, the authors use data on 473 DRGs from 28 counties in Washington state to study the nature of variability. The variation was higher for the more prevalent DRGs, suggesting that adjusting for prevalence may be reasonable. The true coefficient of variation appears to be a "natural" measure of variation, but the usual small area variation statistics do not provide good estimates of the true coefficient of variation. A new estimate is proposed that can be used to compare and test the variability of several DRGs. PMID- 8492586 TI - Geographic variation of procedure utilization. A hierarchical model approach. AB - In this study, an abbreviated introduction to hierarchical statistical models for quantifying and explaining variations in the utilization of medical care is presented. The illustrative example was derived from an analysis of interstate variation in coronary angiography utilization for Medicare patients with a recent acute myocardial infarction. The hierarchical model distinguished within-from between-states variation: the former was modeled via a separate logistic regression for each state, with age and sex as the independent variables, while the latter was modeled via a multivariate normal distribution for the coefficients of the state-specific logistic models. Alternative computation approaches were compared and model fit was assessed. Estimates of the distribution of state rates of angiography for an average patient and for age-by sex strata were obtained. The results showed substantial interstate variation in angiography utilization, but only moderate interstate variation in the effects of age and sex on the decision to perform angiography. This analytic approach allows substantially more detailed results than those by standardization, and accounts for sample size differences between units of aggregation. The next major step in the analysis would be to derive smoothed estimates of the individual state logistic models by pooling data across states. The analysis can also be extended to incorporate other patient characteristics, such as race and comorbidity, and state characteristics, such as geographic location and availability of the procedure. PMID- 8492587 TI - Linking patients to hospitals. Defining urban hospital service populations. AB - Small area analysis is a widely used approach for identifying variations in the delivery of health services across geographically defined populations. There is growing consensus that, to a significant degree, these variations reflect the practice style of different physicians at area hospitals. However, to date, small area analysis has not been appropriate for studying the practice style of physicians at individual urban hospitals. This occurs, at least in part, because urban residents have easy geographic access to several hospitals, and no clear method of assigning small geographic areas to a single hospital is available. This study addresses this issue by taking a new approach to defining urban hospital service areas. As gate keepers to hospitals, physicians tend to admit their patients to one or two institutions. Therefore, urban hospital service areas are defined by ignoring geographic boundaries and linking patients to a single hospital on the basis of the admitting patterns of the physicians the patient contacts. The sensitivity of the assignment rules is tested; the results of the proposed technique are compared with those using a traditional geographic approach. The findings of the study reported here suggest that this is a feasible method, which yields stable sensitivity results and is generalizable to a variety of urban settings. PMID- 8492588 TI - Regional mapping of incidence rates using spatial Bayesian models. AB - This study takes a statistical-modeling point of view to the assessment of health care services and procedures. The emphasis is on small-area prediction of incidence rates from spatially contiguous regions, although suitable modifications can also give doctor-level predictions. The main idea is to recognize the individuality of each region through a spatial Bayesian model for incidence rates. A noise component, because of location error and measurement error, is filtered out using empirical Bayes methods. The resulting smoothed predictors of incidence rates provide an accurate picture of the health care service or procedure under investigation. PMID- 8492589 TI - Bayesian predictive inference for units with small sample sizes. The case of binary random variables. AB - The National Health Interview Survey is designed to produce precise estimates for the entire United States but not for individual states. In this study, Bayesian predictive inference is used to provide point estimates and measures of variability for the desired finite population quantities. The investigation reported here concerns binary random variables such as the occurrence of at least one doctor visit within the past 12 months. The specification is hierarchic. First, for each cluster, there is a separate logistic regression relating a patient's probability of a doctor visit with his or her characteristics. Second, there is a multivariate linear regression linking the (cluster) regression parameters to covariates measured at the cluster level. A fully Bayesian analysis is carried out; this technique provides gains over synthetic estimation and conventional randomization-based analysis. The reported approach is potentially useful for any situation when the sample size associated with a unit of interest (e.g., a hospital or small geographic area) is too small to permit satisfactory inference using only the data from that unit. PMID- 8492590 TI - An introduction to multiple time series analysis. AB - An expository account of multiple time series analysis is presented. Modeling several related time series together makes it possible to ascertain dynamic leading, lagging, and feedback relationships among the series; to produce more efficient forecasts and, in some situations; to develop control schemes. Procedures for building linear vector autoregressive moving average models are sketched and illustrated. An extension to parallel vector time series in a hierarchical framework is given. PMID- 8492591 TI - Future directions for small area variations. PMID- 8492592 TI - Patient practice variation. A call for research. AB - This article presents a theoretic framework, "patient practice variation," currently missing from the investigations of medical care variation. Resource utilization, immediate, and long-term outcomes may be better explained by including utilities under control of the patient into small area variation studies. This especially may be important in the area of prenatal and maternal care and certain chronic diseases, such as diabetes. The quality of care measures must incorporate patient satisfaction and quality of life in addition to more objective physiologic outcomes. PMID- 8492593 TI - Variations research. The physician perspective. PMID- 8492594 TI - On defining small areas. AB - This study explores the relationship between small area and economic approaches to defining hospital markets. Both approaches attempt to link populations receiving care with providers who deliver it. The approaches differ fundamentally, however, in their view of the role of alternative sources of inpatient services. The small area approach attempts to minimize the number of hospitals in a market. Economic approaches attempt to include substitute sources of care. The economic literature also suggests that the availability of substitutes influences the use of health services. This literature is briefly reviewed, and the implications for the analysis of physician practice patterns are discussed. The study concludes that economic approaches to market definition are likely to be more fruitful in explaining variations in the use of services. PMID- 8492595 TI - Data bases for variations research. PMID- 8492596 TI - [Evaluation of the nutritional status through determination of anthropometric parameters: new charts for the working population of Catalonia. Group for the Evaluation of body composition in the population of Catalonia]. AB - BACKGROUND: Body composition measure by anthropometric parameters permits the detection of populations at risk of developing diseases with greater impact in public health and provides standard values of normality of nutritional state. METHODS: A prospective transversal study was carried out with a randomly selected sample of 6,445 individuals taken from 25,279 workers evaluated in Safety and Hygiene Centers during 1990. Chronically ill patients were excluded with 5,019 healthy individuals between 16 and 65 years of age being selected. The following data were obtained: height, weight, skin fold of the biceps and triceps, subscapular and abdominal and arm perimeter. Calculation of the weight/height, weight/height, weight/height, sum of two and four folds, mid-arm muscle circunference, area fo the arm, muscle area of the arm, adipose area of the arm and muscle adipose index was performed. RESULTS: The tables of the percentiles 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99 of the anthropometric parameters according to sex and age are presented. Significant differences were found among the age groups for the fat parameters which were greater from the third decade for the fold of the fat of the trunk in males and from the fourth decade of the fat parameters of the trunk and extremities of females. The muscle parameters successively increased in both sexes and for each age group up to the fourth decade and thereafter remained stable. CONCLUSIONS: The values of the anthropometric parameters may be used as standard patterns of the working population in Catalonia. The differences between sexes and age groups, such as with the values of the Catalan population previously referred and those of the American population, indicate that the anthropometric measurements of body composition must be periodically determined to ensure adequate standards of each population. PMID- 8492597 TI - [Anthropometric reference parameters for the aged population]. AB - BACKGROUND: Anthropometry is an effective method used in the evaluation of the state of nutrition. Anthropometric reference values obtained from the general population have frequently been used. The aim of this study was to determine the anthropometric parameters of the elderly in Manresa and demonstrate the different evolution of these values in both sexes between the ages of 65 and 85 or more. METHODS: Following randomization a representative sample of 1,034 healthy elderly subjects living in Manresa was obtained with the following being determined: weight, height, tricipital, subscapular and abdominal fat folds, arm circumference, arm muscle perimeter, weight/height indexes, muscle and fat areas of the arm and percentage of fat. All the measurements were obtained by the same person with the use of a tallimeter scale with a flexible metric tape and a Holtain lipocalibrater. RESULTS: The values are presented in percentiles by subgroups of age and sex. The weight, height and indexes of lean mass were greater in males while those determining fatty mass were greater in females. In females all the values decreased between 65 and 85 or more years of age (p < 0.001), while in males all decreased (p < 0.001) except; tricipital and abdominal skin folds. Upon comparison of these parameters with those obtained in other geographic areas, differences were observed between both. CONCLUSIONS: By the characteristics of the population studied it was considered that the anthropometric parameters obtained are extensible to all the elderly population of Catalonia and may be used as reference values of the same. PMID- 8492598 TI - [Prevalence of hyperalphalipoproteinemia in the general population]. AB - BACKGROUND: Hypercholesterolemia is often incorrectly treated with no normal consensus being followed. The same occurs with hyperalphalipoproteinemias (HAL). The aim of the present was to know the prevalence of HAL in a sample of an adult general population and the theoretical percentage of the same which would be treated as hypercholesterolemia if the above cited entity is not appropriately diagnosed. METHODS: A transversal study (November 1991-March 1992) was performed selecting a randomized sample representative of the adult population (13,224 individuals) from a basic health area (municipal census of 1991), and was stratified by groups of age and sex. The final sample was of 802 individuals who underwent anamnesis and in whom total cholesterol (TC), total triglycerides (TG), cHDL and cLDL were determined. In agreement with the percentile 90 of the results of the Lipid Research Clinic Programs for each group of age and sex with normal number of cLDL (3.84 mmol/l, < 150 mg/dl) and TG (2.27 mmol/l, < 200 mg/dl) the percentage of the population with HAL was established. The theoretical percentage of the population which would be treated as hypercholesterolemia was found following the recommendations of the Spanish consensus without the cHDL and cLDL being calculated. RESULTS: The prevalence of HAL was 7.8%, 92% being primary and 7.9 secondary. By ages the greatest frequency appeared in the group of 20-29 years (15.8%) and 30-39 years (8.4%) with male predominance (9%) with respect to females (6.8%). 63.5% had hypercholesterolemia. Treatment would be recommended to 661 individuals without need. CONCLUSIONS: Hyperalphalipoproteinemia is a frequent entity in general population. Correct diagnosis would avoid unnecessary treatment in 5% of the population. The determination of cHDL is required before any hypolipemic treatment is initiated. PMID- 8492599 TI - [Growth factors in the pathogenesis of liver cirrhosis]. PMID- 8492600 TI - [Dying in April: a reflection on the reality of Spanish health care]. PMID- 8492601 TI - [Clinical use of hematopoietic growth factors (hematopoietins)]. PMID- 8492602 TI - [Study of the autonomic nervous system by evaluation of pupillary function]. PMID- 8492603 TI - [Drug-induced agranulocytosis: response to treatment]. PMID- 8492604 TI - [Ceftriaxone in the ambulatory treatment of bacterial infections]. PMID- 8492605 TI - [Impact of the new CDC classification of HIV infection and AIDS]. PMID- 8492606 TI - [Consideration on the situation of microbiology and microbiologists in public hospitals]. PMID- 8492607 TI - Thyroid cancer. AB - Management of thyroid cancer varies somewhat between communities and institutions depending on tumor type and individual treatment philosophy. The differentiated thyroid cancers have a significantly better outlook than the medullary and anaplastic. This article provides an overview of the literature that describes pathogenesis, diagnosis, and treatment currently recommended for these thyroid cancers. PMID- 8492608 TI - Airway obstruction. New modalities in treatment. AB - The key to successful therapy of airway obstruction is always to first secure the airway. The primary care physician needs to understand the airway anatomy and the causes of airway obstruction. As a team, the primary care physician and the otolaryngologist can evaluate and treat these disorders. PMID- 8492609 TI - Voice disorders. AB - Many other diagnoses and treatments are of particular importance in caring for voice patients. Those discussed in this article are among the most common. The exacting demands of a professional singer or actor, his or her acute ability to analyze the body's condition, and his or her professional athlete's need for a nearly perfect result provide special challenges and gratification for physicians. However, a great many of our non-singer/actor patients are also extremely dependent on voice quality and endurance. Consequently, every patient with a voice complaint should be treated as Pavaroti or Sutherland would be treated, and every voice evaluation should be carried out systematically until a diagnosis has been made on the basis of positive evidence. The emergence of interdisciplinary teams, advanced instrumentation, and voice laboratories has made dramatic improvements in the standard of voice care, and the rapid development of voice as a subspecialty promises continuing advances in the care of voice disorders. PMID- 8492610 TI - Swallowing disorders. Diagnosis and therapy. AB - Normal swallowing is a complex, rapid neuromuscular function. Causes for dysfunctional swallowing are protean. Appropriate workup includes a careful history, thorough physical examination of the head and neck, videofluorographic swallowing study, and when appropriate, manometry and endoscopy under anesthesia. Many swallowing problems are not easily curable or reversible, but most patients experience some improvement through the intensive efforts of a multidisciplinary team. The otolaryngologist-head and neck surgeon plays a key role in both evaluation of patients with dysphagia and in surgical intervention for selected cases of cricopharyngeal motor dysfunction and chronic aspiration. PMID- 8492611 TI - Sensitizers of photoradiation and ionizing radiation in the management of head and neck cancer. AB - PDT and IUdR-sensitized radiation therapy represent potential advances in the treatment of tumors of the head and neck. Light-activated photosensitizers have definite antitumor activity in both in vitro and in vivo experimental systems. Much of the early clinical work in head and neck cancer involved treatment of patients with advanced, recurrent disease who had not responded to conventional therapy. Because of the limited light penetration in tissue and infiltrative nature of most recurrent lesions, little effective palliation was seen in these advanced cases. More success has been achieved in the treatment of earlier, more superficial lesions, and active investigation continues in this area. Current research is aimed at defining the most appropriate sites and applications for the technique. HpD and DHE are currently only approved for use as investigational compounds in clinical studies. If ongoing trials of PDT in the treatment of superficial bladder cancer, obstructing esophageal cancer, and non-small cell lung cancer show encouraging results, an application will be made to the Food and Drug Administration for approval of DHE as a photosensitizer for general clinical use for these indications. Laboratory work to better understand the mechanism of action of HpD also continues, as well as investigations into alternative photosensitizers with improved tumor localization, less cutaneous photosensitivity, and absorption peaks at deeper penetrating wavelengths of light. A pilot program evaluating IUdR-sensitized radiation therapy for treatment of advanced head and neck cancer is in progress. If encouraging early results continue to be observed, a randomized trial comparing IUdR-sensitized radiation therapy with conventional radiation therapy can be conducted. Hopefully, these developments in the field will improve the therapy for patients with head and neck cancers. PMID- 8492612 TI - Nutritional management of the head and neck cancer patient. AB - Approximately one third of patients with advanced cancer of the head and neck are severely malnourished. Another one third of patients suffer from mild malnutrition. Adequate nutritional support given before cancer therapy will reduce therapy-related complications in severely malnourished patients. Patients who are less severely malnourished should receive definitive cancer therapy promptly with concurrent concern for nutritional support. Advantages of nutritional support are that patients feel better, have a higher tolerance to therapy with fewer complications, and achieve a higher response rate to therapy. The disadvantages to such a program are modest but real. This therapy is expensive and it is hard to prove its long-term benefit. Attempting treatment may be frustrating in poorly motivated patients. Appropriate delivery of nutritional support in selected patients has been determined as highly rewarding to the physician. PMID- 8492613 TI - Role of fine-needle aspiration in the evaluation of neck masses. AB - Fine-needle aspiration has assumed a large role in the evaluation of head and neck masses. It has been found to be simple, quick, accurate, and cost-effective in the workup of patients with unknown head and neck masses. This article reviews these advantages and the role of fine-needle aspiration in the evaluation of head and neck masses. PMID- 8492614 TI - Update on immunology of head and neck cancer. AB - The history of immunotherapy in head and neck cancer is filled with disappointing results and clinical trials of nonspecific immunotherapeutic protocols. Most of these protocols did not concern themselves with some of the possible underlying etiologies of immunosuppression, such as alcoholism, malnutrition, aging, and the oncologic therapies that the patients were undergoing. These factors must be appreciated, and attempts must be made to deal with their devastating effects. It is also becoming increasingly apparent that the humoral immune system does have a major impact on the effectiveness of the cellular immune system, and that the various components of this system need to be more fully understood. The complexity of these interactions will probably not allow for an effective immunotherapeutic protocol to be attained in the near future. It is, however, more likely that the establishment of immunoprognosis and immunodiagnosis may be achieved as these complex interactions are more fully identified and understood. PMID- 8492615 TI - Phonosurgery for voice improvement and restoration. AB - Recent advances in laryngology have occurred simultaneously in both the diagnostic and therapeutic realms. The advent of sophisticated voice laboratories with the ability for in-depth analysis of voice disorders has provided insights into their pathophysiology necessary to develop sophisticated procedures to treat them. Experience with these procedures has likewise provided new understanding of laryngeal function. Together these diagnostic and therapeutic modalities have allowed unprecedented advancement in treating laryngeal disorders, hitherto treated in a most unsatisfactory manner. PMID- 8492616 TI - Current trends in rhinoplasty and the nasal airway. AB - The current trends in rhinoplasty and the nasal airway are discussed. The rhinoplastic ideal is that which is aesthetically pleasing while maintaining or improving the physiologic functions of the nose. It is important for the primary care physician to understand the different aspects of rhinoplasty so that he or she may determine which patients will have success with this surgery. Furthermore, the primary care physician will have a better understanding of what the surgeon tries to achieve with rhinoplasty surgery. PMID- 8492617 TI - Surgery of the aging face. Advances and functional considerations in facial plastic surgery. AB - With an aging patient population, many more individuals will seek advice from a trusted primary care physician regarding improvement of their appearance and related functional considerations. The physician plays a key role in understanding patients' concerns, counseling their needs and desires, and recognizing the important psychological benefits associated with surgery of the aging face. Recent advances and techniques for both aesthetic and functional problems have made surgery for the aging face safer, more precise, and more predictable, resulting in a much more positive outcome. By keeping in mind the preoperative assessment, indications, and specific procedures discussed in this article, many patients referred for consideration should enjoy the benefits of rejuvenation surgery of the aging face. PMID- 8492618 TI - Microvascular reconstruction in the head and neck. AB - Microvascular surgery provides a new frontier in head and neck reconstruction. Restoration of form and function in patients undergoing radical surgery for head and neck malignancies is now possible to a degree that was previously unattainable using other methods of reconstruction. Massive soft tissue and bony defects can now be reconstructed in a single stage procedure with superior functional results. The investment of increased time and effort in the operating room can produce a substantial benefit for the patient. PMID- 8492619 TI - Hair replacement surgery for male pattern alopecia. AB - Male pattern alopecia is the most common type of hair loss encountered. Although this malady has no direct adverse consequences on physical health, physicians should be aware of the impact hair loss may have on a man's self-esteem. This type of hair loss and current hair replacement surgical techniques are discussed. PMID- 8492620 TI - [New methods must be used in the treatment of patients with stones]. PMID- 8492621 TI - [Simplicity contra essentials as a problem in psychiatry]. PMID- 8492622 TI - [Computerization of records in child health services--consultation is important]. PMID- 8492623 TI - [Sarcopenia--an old age disease possible to treat]. PMID- 8492624 TI - [The Dala model--a political bullet]. PMID- 8492625 TI - [Many prescriptions never reach the pharmacy]. PMID- 8492626 TI - [One more building stone in publishing ethics]. PMID- 8492627 TI - [Urinary incontinence in women. What is promised by the guarantee of care?]. PMID- 8492628 TI - [Severe idiopathic constipation in adults. A diagnostic and therapeutic challenge]. PMID- 8492629 TI - [Hypofractionation. A method for stereotaxic radiation of major brain lesions with linear accelerator]. AB - Fifteen patients with brain tumours or arteriovenous malformations (AVMs) underwent hypofractionated stereotactic irradiation, 2-5 fractions being delivered using a linear accelerator and a non-invasive stereotactic frame. Results of the treatment of brain metastases were comparable with those reported for single fraction radiosurgery. With the AVMs, the rate of obliteration would seem to be slower than that after radiosurgery, perhaps because the irradiated volumes in our study were significantly larger than those treated with radiosurgery. An advantage of hypofractionated stereotactic irradiation is that larger brain lesions can be treated than is appropriate with radiosurgery. PMID- 8492630 TI - [Mycobacterial lymphadenitis. A differential diagnosis to be considered regardless of age]. PMID- 8492631 TI - [Laparoscopic surgery. Epoch-making progress or adventurous experimental activity?]. PMID- 8492632 TI - [Risk of Legionella is often underestimated]. PMID- 8492633 TI - [Exotic tinea. Increased occurrence among children in the district of Stockholm]. PMID- 8492634 TI - [Does competitive skiing cause asthma? Cold air is suspected to be the primary cause. Interview by Birgit Wilhelmson]. PMID- 8492635 TI - [Treatment of prostatic cancer (Drug Administration, Sweden)]. PMID- 8492636 TI - Demonstration of the myocardial salvage effect of lithospermic acid B isolated from the aqueous extract of Salvia miltiorrhiza. AB - Lithospermic acid B has been isolated to > 95% purity by high performance liquid chromatography from the aqueous extract of the roots of Salvia miltiorrhiza. When infused at 5.5 mumoles/kg into the post-ischemic rabbit heart, it reduced by 62 +/- 10% (n = 8) the myocardial damage found in the saline control in a rabbit ischemia-reperfusion model. PMID- 8492637 TI - Role of 5-HT1A receptors in the forced swimming wheel test in reserpine-treated mice. AB - The antidepressant-like effect of 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH DPAT), a selective 5-HT1A receptor agonist, was studied in the forced swimming wheel test in reserpine-treated mice. 8-OH-DPAT and the antidepressant imipramine, dose-dependently increased the number of turns of a water wheel made by mice. This effect of imipramine (30 mg/kg, i.p.) was enhanced by reserpine treatment 24 hr before the test. The effect of 8-OH-DPAT (0.3 mg/kg, i.p.) was also enhanced in reserpine-treated mice. This enhanced effect of 8-OH-DPAT was blocked by pretreatment with the 5-HT1A receptor antagonists, (-)-propranolol (3 mg/kg, i.p.) and NAN-190 (1 mg/kg, i.p.), but was not blocked by a beta-blocker, (-)-atenolol (3 mg/kg, i.p.). 8-OH-DPAT did not affect locomotor activity in the reserpinized mice and did not affect the reduction of monoamine content induced by reserpine. These results suggest that the effect of 8-OH-DPAT in increasing the number of turns of the wheel made by mice was exerted through a 5-HT1A receptor and that this effect did not reflect only changes in the locomotor activity of the mice. PMID- 8492638 TI - Age-related impairment of early and late events of signal transduction in mouse immune cells. AB - The effects of aging were studied on both early and late [subsequent to activation of protein kinase C (PKC)] events of signal transduction in mouse T cell subsets. Aged C57Bl/6 mice showed significant suppression of Con A stimulated Ca2+ mobilization in both CD4+ and CD8+T cells compared to young mice. When early signaling was bypassed by stimulating cells with the combination of a calcium ionophore and a phorbol ester. [3H]thymidine incorporation was comparable between young and aged mice while Con A-stimulated [3H]thymidine uptake remained depressed in aged mice. These results suggest that impairment of early (but not late) events may be responsible for the suppression of T cell proliferation in aged animals. Further, aged mice exhibited a significant increase in spontaneous proliferation resulting in a robust reduction of the stimulation index of both Con A and PMA/A23187-induced proliferation. Similarly, aged mice exhibited a significant increase in spontaneous IL-2R expression in both CD4+ and CD8+ T cells. No differences in IL-2 secretion were found between young and aged mice. The change in IL-2R expression was positively correlated with increased spontaneous proliferation. Overall these results suggest that: 1) impaired early (pre-PKC) rather than later (post-PKC) events of signaling may be responsible for poor proliferation of T cells, and 2) endogenous activation of cells related to increased level of IL-2R expression may play an important role in aging associated immunosuppression. PMID- 8492639 TI - Aging and 3H-paroxetine binding in rat brain: effect of imipramine and tetrahydroacridine. AB - 3H-Paroxetine (PA) binding was studied in the frontal cortex (FC) and hippocampus (H) of 4 mos (young), 15 mos (adult) and 24 mos (aged) old Fischer 344 rats. Bmax (maximum number of binding sites) of PA binding was significantly higher in the H of adult rats compared with either young or old rats. There was no difference in Bmax between young and old rats. No change in Kd was observed in H and Kd or Bmax in FC with age. We also studied the effect of imipramine and tetrahydroacridine (THA) on PA binding in FC and H. Both drugs inhibited PA binding in FC and H but THA was 2000 times less potent than imipramine. There was no effect of age on IC50 values of imipramine and THA. These observations suggest that the number of 5-HT transporter sites in the hippocampus increases with brain maturity but then drops significantly during old age. This finding may have implications for age related decrements in learning and memory, thought to be mediated by hippocampal structures. PMID- 8492640 TI - Ouabain--a local, paracrine, aldosterone synthesis regulating hormone? AB - 10(-4) M ouabain increases aldosterone production at 3.6 and 5.4 mM potassium concentrations, whereas at high potassium concentration (7 mM) even lower concentration of ouabain (10(-8) M) decreases it. As ouabain has been shown to be produced by the adrenal cortex, a local paracrine regulation of aldosterone production by ouabain is suggested depending on extracellular potassium concentration. PMID- 8492641 TI - Thymic peptide protects vascular endothelial cells from hydrogen peroxide-induced oxidant injury. AB - Oxidant injury of the vascular endothelium is considered an early event in the pathogenesis of atherosclerosis. In this study, the antioxidant effect of a 6-kDa thymic peptide (TP), isolated from calf thymus, was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of TP for 24 h, washed, and then exposed to hydrogen peroxide (H2O2) for 2 or 4 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric acid fluorometric assay. H2O2 (120 or 240 microM) incubated with PAEC decreased cell viability, increased LDH release, and elevated MDA production. Preincubation of PAEC with TP (25-150 micrograms/ml) before H2O2 exposure significantly increased cell viability, decreased LDH release, and reduced MDA production. These results demonstrate that TP can protect vascular endothelial cells from oxidant injury. The data thus suggest that TP may be useful for the prevention and/or treatment of atherosclerosis, and further suggest that immune modulating agents may directly or indirectly influence the functions of vascular endothelium. PMID- 8492642 TI - Comparison of antitumor activity of vitamins K1, K2 and K3 on human tumor cells by two (MTT and SRB) cell viability assays. AB - Vitamin K (VK) congeners (VK1, VK2, and VK3) have been used as antihemorrhagic agents, while VK3 has also been found to inhibit growth in various rodent and human tumor cells. We have compared the antitumor activities of vitamin K1, K2, and K3 against a panel of human cancer cell lines. For each test agent, a dose response profile was generated by using an MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide) and an SRB (sulforhodamine B) assay. Both assays yielded similar results. The respective ID50 values of VK3 in five hepatoma cell lines, HA59T, HA22T, PLC, HepG2, and Hep3B, of increasing differentiation state, were 42, 36, 28, 27, and 20 microM. For nasopharyngeal carcinoma (CG1), leukemia (U937), oral epidermoid carcinoma (KB), and breast carcinoma (BC-M1) cells, the ID50 values of VK3 were 26, 15, 25, and 33 microM, respectively. For all the above cells, the ID50 values of VK1 ranged from 6 to 9 mM, and the ID50 values of VK2 ranged from 1 to 2 mM. Thus, the relative potencies of antitumor activity of VK3 compared to VK2 and to VK1 are about 60- and 300-fold, respectively. These results support the preference for use of VK3 over VK1 and VK2 in cancer therapy. PMID- 8492643 TI - Bromocriptine effects on plasma luteinizing hormone and its responses to gonadotropin-releasing hormone in normal men. AB - Secretory changes in plasma pituitary luteinizing hormone (LH) after administration of a dopaminergic drug were studied in five normal men. Each subject received orally 5 mg of bromocriptine (Brc) daily for 8 weeks. Each received gonadotropin-releasing hormone (GnRH) stimulation tests at the beginning (control), and at 2, 4, 6, and 8 weeks after initiation of Brc treatment. We referred the basal plasma LH and a ratio of maximally GnRH-responded plasma LH to its basal level (R-Max) as indicators of secretory alterations of the LH. Mean basal levels of plasma LH in the five subjects at the beginning and those of R Max were 3.4 +/- 2.3 (SD) mIU/mL and 8.5 +/- 2.9 units, respectively. Statistically, both the mean values of plasma LH and R-Max during the control period did not differ significantly from those obtained after Brc treatment, although mean basal levels of plasma prolactin during the control period (15.6 +/ 4.6 ng/mL) decreased significantly (p < 0.05) after initiation of treatment. A low dose of Brc administered to normal men for 8 weeks does not significantly influence pituitary secretion of LH. PMID- 8492644 TI - Comparative and consistent approaches to exploratory research. PMID- 8492646 TI - Pharmaceutical companies testing 91 AIDS drugs. PMID- 8492645 TI - Family libraries: supporting patient education. PMID- 8492648 TI - An integrated approach to incorporating research findings into practice. PMID- 8492647 TI - Depo-Provera. PMID- 8492649 TI - Family violence. PMID- 8492650 TI - Demands of labor, not conflicts, cause mothers to "hold back". PMID- 8492651 TI - Heparinized saline or normal saline as a flush solution in intermittent intravenous lines in infants and children. PMID- 8492652 TI - Epidural anesthesia in the maternity patient. PMID- 8492653 TI - A step up from home: enhanced care for medically complex HIV infected children. PMID- 8492654 TI - Home care of the pregnant woman using terbutaline. PMID- 8492655 TI - Drugs and decomposition. PMID- 8492656 TI - Evaluating the variability of duplicate breath alcohol analyses as a function of subject age. AB - The influence of the person's age upon reproducibility in duplicate breath alcohol analyses is investigated. A total of n = 30,324 duplicate results (with both > or = 0.01 g/210L) were selected and divided into eight age groups from 10 19, 20-29, and up through 80+. Two duplicate agreement criteria, +/- 10% of the mean and +/- 0.02 g/210L, were evaluated according to age. A X2 trend analysis was employed and resulted in: +/- 10% of mean criteria, P < 0.001 and +/- 0.02 g/210L criteria, P > 0.05. The proportions of duplicates not conforming to the two agreement standards along with 95% confidence intervals were: +/- 10% of mean, 0.026 (0.024 to 0.028) and +/- 0.02 g/210L, 0.052 (0.050 to 0.054). Depending on the agreement criteria selected there will be proportional differences, but neither appears to be importantly influenced by the subject's age. The breath sampling criteria employed in the instrument studied does not appear to inhibit acceptable agreement, even in elderly subjects where the risk of respiratory disfunction increases. PMID- 8492657 TI - Forensic medicine in Panama. PMID- 8492658 TI - Production of monoclonal antibodies against diquat and its enzyme-linked immunosorbent assay. AB - Monoclonal antibodies(MoAbs) very specific to diquat (DQ) were produced. An immunogen was synthesized by binding DQ to bovine serum albumin via a diazo coupled derivative. BALB/c mice were immunized i.p. monthly with 0.25mg of the immunogen for five months. Their spleen cells were fused with P3U1 myeloma cells and hybridoma clones secreting MoAbs were obtained. Two MoAbs were selected and subtyped to be IgM and IgG3. The MoAbs recognized DQ but did not bind to paraquat and other analogues at all. A datum obtained from a clinical sample demonstrates that an enzyme-linked immunosorbent assay system using one of the MoAbs is useful in the practice of toxicological analysis. PMID- 8492659 TI - A study of 133 suicides among Canadian federal prisoners. AB - This paper reviews the literature on prison suicide. The characteristics of suicide within the Canadian Federal Penitentiary Service are compared with previous data. In the population examined, prison suicide was found to be a predominantly male phenomenon, not associated with age, offence type, previous convictions or length of sentence. It was most commonly committed by hanging, frequently occurring in the period shortly after sentencing. Suicide was associated with single marital status, earlier suicide attempts, a history of drug or alcohol abuse, and a previous history of psychiatric illness. PMID- 8492660 TI - Comparative suicide rates in different types of involuntary confinement. AB - In the past decade especially, a number of studies have appeared on suicide among court-involved persons, chiefly in jail and prison remand settings, and to a lesser degree among longer-term prisoners. Confinement is not everywhere equally suicidogenic, and the types of people who find themselves confined do not represent uniformly high risk groups. This article reports on rates of completed suicides over long periods of time in two very different US institutions operated by the Massachusetts Department of Correction: the Addiction Centre and its antecedent facilities (1886-1990); and the Defective Delinquent Department (1922 1971). For perspective, the paper compares suicide rates among its two populations to rates for other very distinctive institutions operated by the Massachusetts Department of Correction, the Bridgewater State Hospital and the Massachusetts Treatment Centre for Sexually Dangerous Persons. The results are remarkable for the rarity of suicide in three distinct populations--the Addiction Center, the Defective Delinquent Department and the Treatment Center for Sexually Dangerous Persons--but considerably higher rates in the State Hospital, a population often dismissed as 'criminally insane.' The possible significance of these results for debates about 'importation' versus 'deprivation' explanations of custodial suicide is discussed. PMID- 8492661 TI - Suicide among forensic psychiatric patients. AB - This paper examines the problem of suicide among patients discharged from a Regional Secure Unit. The stereotype that emerges is a young man with anti-social personality traits, suffering from an affective psychosis, with a history of substance abuse and impulsive violence directed both towards himself and others, who is alienated from care staff and social supports because of his provocative and uncooperative behaviour. In contrast with the general population, forensic patients are more likely to commit suicide using a violent method and are more likely to have a suicide verdict recorded by the coroner. The implications of these findings for treatment and preventive interventions are discussed. PMID- 8492662 TI - Aggressive behaviour among patients referred to a psychogeriatric service. AB - The characteristics of a series of patients referred to a psychogeriatric service over a one-year period were examined. Patients exhibiting aggressive behaviour as a feature of the presentation were compared to those without. Aggressive patients were less likely to be living in their own homes, less likely to receive services, more likely to be referred from social services institutions, and be on multiple psychotropic drugs, particularly neuroleptics. The implication of this for adequate provision of psychiatric and social service is discussed. Only a small number of patients exhibited aggressive behaviour as a feature of their presentation. PMID- 8492663 TI - An end to D-I-Y cremation? AB - This article examines whether to be lawful a cremation must be carried out in accordance with the Cremation Acts. It argues that it need not be but points out that any lacuna in the Acts will be plugged if and when the new consolidated Cremation Regulations are passed. It then considers the implication of this reform for the disposal of babies born dead before the legal age of viability. PMID- 8492664 TI - Helen's ankles: some speculations on what we miss in criminal history. PMID- 8492665 TI - Homicide followed by suicide (dyadic death) in Yorkshire and Humberside. AB - In England and Wales 5-10 per cent of homicides are followed by the suicide of the assailant. Fifty-two episodes of homicide-suicide occurring in Yorkshire and Humberside have been studied. Forty-nine of the assailants were male with a mean age of 49 years. There were 65 victims, who were usually the spouse and/or children of the killer. Shooting was the most frequent method of killing and subsequent suicide. The results are compared with other homicide statistics and previously published studies of homicide-suicide. PMID- 8492666 TI - Cot death and anal abuse--(was I right in disregarding the alleged anal abuse?). PMID- 8492668 TI - False confession, false evidence--can psychiatrists assist the courts? PMID- 8492667 TI - A load of rubbish. PMID- 8492669 TI - National Health Service. PMID- 8492670 TI - Seclusion theory reviewed--a benevolent or malevolent intervention? AB - The Special Hospital Service Authority for England and Wales undertook an extensive international literature review on seclusion as a basis for a proposed extended research project on seclusion in the Special Hospital system. The review highlighted the theoretical foundations of seclusion to be based on therapy, containment or punishment; however, there appeared little work carried out in examining the underlying attitude to these central themes. It was suggested that a further level of analysis, by measuring these attitudes along a benevolent malevolent scale, may prove helpful in advancing our conceptual understanding of the role seclusion plays as a psychiatric intervention. PMID- 8492671 TI - [Objectives and results of therapy in a psychiatric day hospital. Follow-up of 70 patients]. AB - Ten years after the institution of a Day Hospital in Rome, the authors make an assessment of treatment results achieved for 70 patients admitted for the first time in 1986 and assessed after five years. Literary studies emphasizing Day Hospital effectiveness are reviewed; then the authors describe the setting in which this research was carried out. The primary aim was: to evaluate the efficacy of this unit to satisfy its users' needs, to permit their reentry into the community and to prevent their relapses and rehospitalizations. PMID- 8492672 TI - [Educational maladjustment: relational aspects]. AB - Educational maladjustment is approached from a systemic point of view and the pupil's problems are therefore considered as the indication of a malfunction in the child-teacher-parent system. The possibilities of using psychotherapy are examined through the analysis of three case reports. PMID- 8492673 TI - [Psychiatric aspects in dermatology. Clinical contribution]. AB - Three clinical cases of dermatologic involvement in psychiatry are presented and the possible psychodynamic mechanism considered on the basis of the literature. PMID- 8492674 TI - [Body Image Index in the Rorschach test in ulcerative proctocolitis]. AB - The use of the Rorschach test allows the body image to be examined using the Body Image Index formulated by Fisher-Cleveland. This index is obtained by calculating the responses to Penetration and Barrier. The hypothesis is that the diseases which affect the inside of the body are more greatly correlated to a high P score and a low B score (high P-low B type personality). The paper examines the Body Image Index in a sample of 41 patients suffering from ulcerous rectocolitis comprising 24 males and 17 females with a mean age of 32 years. The personality profile obtained is of the "high P-low B" type with a P/R% ratio which is clearly higher than the central mean value (28.7% vs 8%) and a B/R% ratio which is clearly lower than the central mean value (4.2% vs 18%). The personality of the patients in this group was marked by a tendency to anxiety and a tendency to express aggression within their bodies (anger-in) which was field-dependent, difficulty in tolerating stress, a tendency to react somatically to conflicts, a low degree of body image stability and a constant need for an external holding object. PMID- 8492675 TI - [Naltrexone therapy. Experience with "Telephone Assistance" in Rome]. AB - From March 1989 to February 1991, at "Telefono in Aiuto" (USL RM/10), Naltrexone has been used in 271 heroin addict patients. Naltrexone, a pure opiate antagonist, nullifies subjective heroin effects, preventing the setting up of tolerance and physical dependence. By administration for one year to drug-free addicts, it proved to be useful in relapse prevention. Naltrexone seems to be safe and without side-effects. Its effectiveness grows if its use is matched with psychological help. PMID- 8492676 TI - [Sexuality. Cultural, social and clinical aspects]. AB - The deep changes in values, beliefs and behaviour, both individual and group, have been examined, referred to the sexuality, by various methods and prospects. Sexual differentiation, typical of the plast, has been rediscussed and modified. As a result of these changes we can talk about old myths, concerning the conception of sexuality in the past, and new myths that concern the present. In this work we have reviewed the different aspects of male and female roles: masturbation, the obsession abort performance, the orgasm and, not last, the sexuality in old age condition. PMID- 8492677 TI - [Sexuality and psychopathology: aspects of prevention. Cognitive investigation of the sexual information of high school students in Avezzano (AQ)]. AB - Here are reported the final data to out of the analysis of the answers given in a questionnaire distributed to more than a thousand students of the secondary schools of Avezzano before the beginning of a course of sexual information. The questions covered general information (including an opinion on the idea and on the way of treating a course of sexual information at school) such as knowledge of contraceptive methods, the illnesses that are transmitted with sexual acts, the most important rules for the prevention of tumoral pathologies in women and the knowledge of the family's advisory bureau. With a very careful analysis of the answers we have been able to get out very important data about the knowledge that the young people have of sexual arguments (arguments that have guided the successive course of information), and interesting aspects of boys' and girls' psychology with regard to sexual arguments. PMID- 8492678 TI - [Late effects of massive psychic trauma. Holocaust survivors 50 years later]. AB - The authors report the results of a study aimed at examining the present mental state, adjustment and lifestyle of a non-clinical sample of Holocaust survivors aged 60 and over. Most the interviewees have suffered since the war from various psychic symptoms, the so-called "survivor syndrome". Concentration camp survivors form a special group whose level of suffering appears greater and more severe than other survivors. In spite of continuous mental suffering Holocaust survivors have succeeded in adjusting well. They hold top positions at work, are socially successful and have stable family nuclei. They behave as if they need to fulfil the expectations of all those who perished in the Holocaust. Only 4 subjects reported a latency period before the appearance of symptoms. PMID- 8492679 TI - Exercise, health, and aging: a need for more information. 1983. AB - Vigorous exercise is currently being encouraged for health maintenance. There is much evidence that a moderate amount of exercise is needed for the maintenance of functional integrity of the cardiovascular system, muscles, bones, and ligaments. There is also fragmentary evidence of a preliminary nature suggesting that regularly performed exercise may protect against and have beneficial effects on coronary artery disease, diabetes, and hypertension. However, the scientific evidence that strenuous exercise has long-term health benefits or slows aging is meager and unconvincing. Even in the case of coronary artery disease, diabetes, and hypertension, the majority of studies have provided either negative or inconclusive results or have resulted in only minor improvements. Taken together, available evidence is inadequate to serve as a basis for recommending regular participation in strenuous exercise for middle-aged and older individuals. This is particularly true because the theories that exercise may accelerate the aging process as a result of increases in metabolic rate and stress hormone production have never been disproved. Therefore, because of the major public health implications of exercise, large-scale, well-controlled studies of the effects of exercise on coronary artery disease, adult onset diabetes, hypertension, and various aspects of the aging process are urgently needed. Important barriers to progress in this area are the current dearth of exercise physiologists interested in research on health maintenance and well trained in human exercise physiology and the lack of an appropriate research funding mechanism for large-scale, interdisciplinary studies of the effects of exercise on chronic disease processes and aging. PMID- 8492680 TI - Symptomatic hyponatremia during prolonged exercise in heat. AB - Although hyponatremia (HN) has been reported among endurance athletes, its etiology often remains uncertain and of great interest to clinicians and physiologists. This case report presents physiologic evidence regarding the etiology and development of HN during exercise in the heat. A 21-yr-old male volunteer (K.G.) unexpectedly experienced symptomatic HN during a research investigation that involved controlled sodium (Na+) intake (137 mEq Na+.d-1 for 7d) and exercise-heat acclimation (41 degrees C; 30 min.h-1, 8 h.d-1 for 10 d). Fluid balance, physiologic variables, and hematologic/hormone data were measured before and after the HN episode, with similar measurements recorded for nine unaffected volunteers. The results indicated: 1) HN was verified in K.G. (plasma Na+ < 130 mEq.l-1) after only 4 h of mild, intermittent exercise in heat; 2) K.G.'s heart rate, rectal temperature, blood pressure, and Na+ losses in sweat and urine were < or = control subjects at all times; 3) between hours 4-7, an inappropriately large release of vasopressin coincided with a decrease of urine volume to 0 ml.h-1. It was concluded that a large intake (10.3 l.7h-1) and retention (2.77 l.7h-1) of water and a "low normal" initial plasma Na+ (134 mEq.l 1) were primary factors in the development of HN in K.G., whereas Na+ losses in sweat and urine were normal and served only to exacerbate HN. PMID- 8492681 TI - Isolated ganglions of the anterior cruciate ligament. AB - We report three athletes with symptomatic isolated ganglion of the anterior cruciate ligament. The symptoms consisted of anteromedial knee pain, worse when changing direction while running, and on squatting. All gave a history of repeated minor knee trauma without a single episode of serious injury. At day case arthroscopy, a unilobulated cystic mass arising from a clinically and arthroscopically intact anterior cruciate ligament was noted and removed in each case. No further intra- or extra-articular knee lesion was seen. Histology revealed a cystic ganglion in each case. With early physiotherapy, the patients could start gentle training 3 wk after arthroscopy, and, at 6-month review, were fully asymptomatic. A review of the literature shows that an isolated ganglion arising from the anterior cruciate ligament is exceedingly rare, with only three such ganglia having been previously reported. PMID- 8492682 TI - Exercise-induced asthma. AB - Bronchoconstriction associated with exercise can occur in nearly all individuals with asthma and in 35-40% of those with allergic rhinitis/hay fever symptoms. This represents approximately 12-15% of the population. Exercise-induced asthma (EIA) is a clinical syndrome characterized by transient airflow obstruction typically 5-15 min after cessation of physical exertion. Symptoms may include chest tightness, breathlessness, coughing, and/or wheezing. Some individuals may experience delayed bronchoconstriction (late phase response) 6-10 h after completing exercise. Approximately 40-50% of those with asthma exhibit a "refractory period", i.e., diminished bronchoconstriction to exercise performed within 2 h. The pathophysiology of EIA is related to thermal events within the intrathoracic airways. Alterations in the temperature of the airways and/or osmolarity in the epithelial lining fluid cause release of mediators in the airways and the development of bronchoconstriction. Although EIA can be strongly suspected by an appropriate history, pulmonary function testing is necessary to make a specific diagnosis. Measurement of lung function is an important first diagnostic test. If there is no evidence of airflow obstruction at rest, then either bronchoprovocation testing or exercise challenge testing is indicated. Nonpharmacologic therapy includes "warm-up" exercise prior to training or competition to induce a "refractory period" and to prevent/reduce bronchoconstriction. An inhaled beta 2-adrenergic agonist, e.g., albuterol, is usually effective for preventing/treating EIA. Cromolyn sodium is an alternative class of medication that inhibits both the early and late phase responses. Other bronchodilator agents are available if combination therapy with an inhaled beta 2 adrenergic agonist and cromolyn sodium is not effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492683 TI - Effects of iron supplementation and discontinuation on serum copper, zinc, calcium, and magnesium levels in women. AB - The purpose of this study was: 1) to establish the prevalence of depleted iron stores, iron deficiency, and low serum levels for copper, zinc, calcium, and magnesium in a healthy female population; and 2) to examine the effects of iron supplementation and discontinuation on the serum levels of the above minerals. One hundred eleven healthy women between the ages of 18 and 40 yr reported for fasted morning blood sampling for iron, copper, zinc, calcium, and magnesium status. Forty-five subjects were either iron-deficient as defined by a hemoglobin level below 120 g.l-1 (four subjects) or iron deplete as defined by a serum ferritin value below 20 micrograms.l-1 (43 subjects). Two subjects fit both criteria. This subgroup continued with the study and were prescribed a normal therapeutic iron dose (320 mg elemental iron per day, taken as two Slow-Fe tablets.d-1 for a period of 12 wk). The subjects then discontinued the iron supplementation for a further 12 wk. The response of the various blood minerals was monitored at 6-wk intervals. Twenty-five subjects completed the full 24-wk treatment. The main conclusions to be made from this study were that: 1) For this sample population of women, iron depletion was quite common (39%), although low hemoglobin values (< 120 g.l-1) were only seen in 3.6%. No subjects fell below the criteria for low serum copper levels (< 13.3 mumol.l-1) nor low serum magnesium levels (< 0.6 mmol.l-1). Seven subjects (6.5%) fell below the criteria for low serum zinc levels (< 11.5 mumol.l-1) while two subjects (1.8%) were below the criteria for low serum calcium levels (< 2.20 mmol.l-1). 2) Therapeutic oral iron supplementation was successful in raising mean serum ferritin values from 15.9 micrograms.l-1 to 36.5 micrograms.l-1 but was not associated with decrements in serum copper or calcium levels. 3) The treatment did not significantly effect serum zinc and magnesium levels during the supplementation period, but a downward trend continued through the discontinuation phase so that at 18 and 24 wk serum zinc and magnesium levels were significantly lower than baseline. 4) Oral contraceptive use was associated with elevated serum copper and ferritin values and lowered serum magnesium levels. PMID- 8492684 TI - Physical activity, fitness, and selected risk factors for CHD in active men and women. AB - The association of physical activity and cardiovascular fitness with risk factors such as blood pressure, body composition, and smoking habits was evaluated in middle-aged men and women active in sports. Data were available for 2009 men and 898 women, all volunteers over 40 yr of age who were active in sports, were available. Physical activity was recorded as sport activity (number and type of sport, frequency, and duration), occupational activity, and the use of the bicycle for transport. Cardiovascular fitness was expressed as maximal power output (Wmax.kg-1) achieved during a progressive maximal cycle ergometer test. Pearson's product moment correlations between cardiovascular fitness and risk factors indicated significantly lower risks among more fit individuals. Except for smoking habits all risk factors showed better associations with fitness in women than in men. The association of physical activity indicators and risk factors was less strong than the fitness-risk factor association in both genders. In both genders, joggers had the most favorable risk profile compared with subjects who were active in one of the other four most popular sports. We conclude that in this relatively active and healthy population comparable associations of physical activity and cardiovascular fitness with risk factors for cardiovascular disease were found as in studies on less active populations. PMID- 8492685 TI - Cardiovascular responses in persons with paraplegia to prolonged arm exercise and thermal stress. AB - The purpose of this study was to investigate cardiovascular responses in subjects with paraplegia (P) during prolonged upper body exercise in a hot environment. In addition, the effect of the level of the lesion on cardiovascular regulation of persons with paraplegia was studied. Four P with lesions between T2-T6 (P1), five P with T7-T8 lesions (P2), four P with lesions between T9-T12 (P3), and 10 control subjects (C) performed 45-min arm-cranking exercise at 40% of the individual peak power output, in a climatic room at 35 degrees C with a 70% relative humidity. From the 15th to the 45th min, cardiac output (Q) and oxygen uptake (VO2) remained unaltered in all subjects, except a significant decrease of Q in P1. Stroke volume (SV) decreased significantly in both P (-20%) and C (-18%) during the test. Heart rate (HR) increased in compensation for P2 (56%), P3 (65%), and C (55%), whereas HR in P1 did not increase significantly. Hemoglobin concentration changes, representing total plasma volume changes, increased significantly in P2, P3, and C but not in P1. Weight loss and sweat rate increased relative to the sensate skin area and, thus, to the level of the spinal cord lesion (P < 0.01). In conclusion, P with lesions below T6 are able to maintain a stable Q by increasing HR to compensate for the declining SV during exercise in a hot environment. P with lesions above T6 cannot fully compensate for the reduction in SV by an increase in HR, therefore, Q declines. PMID- 8492686 TI - Peak oxygen deficit during one- and two-legged cycling in men and women. AB - The objectives of this study were to determine the relationships of estimated active muscle mass and gender to anaerobic capacity, as measured by the peak oxygen deficit, and to compare these relationships with those for peak oxygen uptake (VO2peak). Fat-free leg volumes (FFLV), and one- and two-legged cycling peak oxygen deficit and VO2peak were determined in young, physically active men (N = 11) and women (N = 9). For men and women, mean (+/- SD) peak oxygen deficit for one-legged cycling (2.27 +/- 0.30 and 1.18 +/- 0.18 l) was 52% of that for two-legged cycling (4.40 +/- 0.62 and 2.25 +/- 0.28 l). For all subjects and both modes of exercise, there was a strong linear relation between peak oxygen deficit (1) and estimated active muscle mass (FFLV) (r = 0.94). This relation was the same in one- and two-legged cycling, but was different for men and women. For a given FFLV, the peak oxygen deficit was significantly higher (P < 0.05) in men than women by an average of 0.44 l. The relation of peak oxygen deficit to FFLV was significantly stronger than the relation of VO2peak to FFLV (r = 0.80). We conclude: (a) that the peak oxygen deficit is strongly related to the estimated active muscle mass during cycling; (b) that for a given estimated active muscle mass (FFLV), the peak oxygen deficit is higher in men than women; and (c) that the peak oxygen deficit is more strongly related than VO2peak to the estimated quantity of active muscle. PMID- 8492687 TI - Influence of recreational activity and muscle strength on ulnar bending stiffness in men. AB - Bone bending stiffness (modulus of elasticity [E] x moment of inertia [I]), a measure of bone strength, is related to its mineral content (BMC) and geometry and may be influenced by exercise. We evaluated the relationship of habitual recreational exercise and muscle strength to ulnar EI, width, and BMC in 51 healthy men, 28-61 yr of age. BMC and width were measured by single photon absorptiometry and EI by mechanical resistance tissue analysis. Maximum biceps strength was determined dynamically (1-RM) and grip strength isometrically. Subjects were classified as sedentary (S) (N = 13), moderately (M) (N = 18), or highly active (H) (N = 20) and exercised 0.2 +/- 0.2; 2.2 +/- 1.3; and 6.8 +/- 2.3 h.wk-1 (P < 0.001). H had greater biceps (P < 0.0005) and grip strength (P < 0.05), ulnar BMC (P < 0.05), and ulnar EI (P = 0.01) than M or S, who were similar. Amount of activity correlated with grip and biceps strength (r = 0.47 and 0.49; P < 0.001), but not with bone measurements, whereas muscle strength correlated with both EI and BMC (r = 0.40-0.52, P < 0.005). EI also correlated significantly with both BMC and ulnar width (P < 0.0001). Ulnar width and biceps strength were the only independent predictors of EI (r2 = 0.67, P < 0.0001). We conclude that levels of physical activity sufficient to increase arm strength influence ulnar bending stiffness. PMID- 8492688 TI - Fibrinolytic and hemostatic parameter response after resistance exercise. AB - These experiments were designed to study the effect of resistance exercise on parameters pertinent to the hemostatic and fibrinolytic systems. Seven normal healthy subjects (6 male, 1 female, 25 +/- 3 yr mean SD) were studied under three conditions: control (C) [no exercise], high volume resistance exercise (HVRE), and low volume resistance exercise (LVRE), which were randomized for each subject, with 7 d separating tests. Both HVRE and LVRE trials encompassed the performance of five sets of nine exercises. After establishing one repetition maximum (1 RM), the HVRE involved the performance of moderate resistance, higher repetition, and shorter resting periods, whereas LVRE involved the use of high resistance, lower repetition, and longer resting intervals. Heart rate (HR) was monitored at rest and continuously during trials and venous blood was removed with minimum stasis, before and immediately after HVRE, LVRE, and before and after 38 min of supine rest (C). The blood was enzymatically analyzed for lactic acid (LA) and assayed using chromogenic substrates for the determination of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), and Factor VIII (FVIII) activities. Global fibrinolysis (GF) was also screened in the fibrin plate and hematocrit ratios were employed to calculate percent plasma volume changes. Values were corrected for changes in plasma volume then data were analyzed using repeated measures ANOVA. There were no significant (P > 0.05) changes in the parameters measured in the resting condition over the three testing occasions and no significant differences (P > 0.05) were observed during the control experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492689 TI - Exercise ventilatory response to upright and aero-posture cycling. AB - The aero-cycling posture has become increasingly popular among cyclists. Because of the potential for altered lung mechanics in the aero-cycling posture, the ventilatory and gas exchange profiles of 10 moderately trained males (31.1 +/- 6.3 yr, mean +/- SD) exercising on a cycle ergometer in the upright posture (UC) and aero-cycling (AC) posture were studied. Exercise consisted of 3-min work stages with 50-W incremental changes until volitional exhaustion. Ventilatory and gas exchange responses to exercise were averaged each minute. Maximal oxygen consumption (54.3 +/- 6.3 vs 53.4 +/- 6.9 ml.kg-1.min-1) in the UC and AC were not significantly different. Maximal values for ventilation (132.5 +/- 32.3 vs 128.0 +/- 28.7 l.min-1), tidal volume (2.7 +/- 0.5 vs 2.6 +/- 0.3 1.br-1), breathing frequency (50.0 +/- 8.0 vs 47.0 +/- 5.0 br.min-1), and submaximal ventilatory and heart rate responses in the UC were not significantly different compared with the AC. No significant difference existed between postures for mean inspiratory flow and inspiratory duty cycle at comparable submaximal power outputs. These results indicate that at absolute power outputs, ventilatory responses, as determined by respiratory pattern and timing, and metabolic cost, were similar in the UC and AC. Thus, the AC does not impair physiologic responses to high intensity exercise. PMID- 8492690 TI - Two seasons of weight cycling does not lower resting metabolic rate in college wrestlers. AB - Over the course of 2 yr, we prospectively studied the effect on resting metabolic rate (RMR) of multiple cycles of weight loss followed by regain in six weight cycling collegiate wrestlers (WC) (mean age = 19.0 yr) compared with 12 weight stable, physically active, nonwrestling controls (C) (mean age = 20.9 yr), whose body composition was similar to the wrestlers. Furthermore, during the second year of the investigation, a group of six nonweight cycling collegiate wrestlers (NWC) (mean age = 18.8 yr) were included in the analyses. The WC had previously undergone at least three seasons of weight cycling and continued this pattern during each year of the study. For the WC, RMR was determined by indirect calorimetry before and after a 6-month season of weight cycling for each of two consecutive years. A similar time frame was followed for measurement of RMR in the C, while for the NWC, pre- and postseason RMRs were measured only during the second year. During the 2 yr, the WC had significantly higher (P < 0.05) pre- and postseason measures of RMR compared with the C. A separate analysis comparing all three groups during the second year showed that RMR was not different for WC and NWC, and that RMR was higher for both wrestling groups compared with C. In this prospective study, weight cycling did not increase the thermogenic efficiency of collegiate wrestlers compared with either nonweight cycling wrestlers or weight stable controls, who were not wrestlers. PMID- 8492691 TI - Estimation of an individual equilibrium between lactate production and catabolism during exercise. AB - During an incremental exercise test after a preceding bout of maximum exercise, blood lactate initially decreases to an individual minimum and then increases again. To determine whether this minimum represents an individual equilibrium between lactate production and catabolism during constant load exercise, the following field tests were performed: in 25 runners and five basketball players (series 1) the speed corresponding to the individual lactate minimum (LM) was measured in test 1 (incremental test after exercise induced lactic acidosis). On two occasions, two constant speed runs over 8 km were performed, one using the LM speed (LMS) (test 2), and another at a running speed of 0.2 m.s-1 above the LMS (test 3). Results of runners/basketball players: blood lactate concentration ([Lac-]B) in test 2 changed from 3.6/4.9 mmol.l-1 to 4.0/4.9 mmol.l-1 during the last 4.8 km, in test 3 from 4.6/4.6 mmol.l-1 to 6.5/6.9 mmol.l-1. These results indicate: 1) the LM speed in test 1 corresponds to a maximum lactate steady state speed during constant load exercise; 2) only a slight speed increase above the LM speed results in continuous marked [Lac-]B increase and earlier exhaustion. Variation of the increment duration in 13 males (series 2) shows no change of the LMS using 800-m and 1200-m increments (4.49 and 4.44 m.s-1) but a marked shift to higher speed using 400-m increments (4.96 m.s-1). Effects of low muscle glycogen stores on the LMS were determined in 10 males (series 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492692 TI - A survey for assessing physical activity among older adults. AB - In 1988, the Yale Physical Activity Survey (YPAS) was designed and then administered to healthy older populations of volunteers (aged 60-86) to establish its 2-wk repeatability and relative validity. Among the 76 volunteers in the repeatability substudy, correlation coefficients between the two administrations of the survey for the eight YPAS summary indices ranged from 0.42 (P = 0.0002) to 0.65 (P = 0.0001). Among the 25 subjects in the validation substudy, weekly energy expenditure (r = -0.47; P = 0.01) and daily hours spent sitting (r = 0.53; P = 0.01) correlated with resting diastolic blood pressure, while the YPAS activity dimensions summary index (composed of questions on vigorous activity, leisurely walking, moving, sitting, and standing) correlated positively with estimated VO2max (r = 0.58; P = 0.004) and inversely with percent body fat (r = 0.43; P = 0.03). The YPAS index of vigorous activity also correlated positively with estimated VO2max (r = 0.60; P = 0.003) and the moving index correlated marginally with body mass index (r = -0.37; P = 0.06). We conclude that the YPAS demonstrates adequate repeatability, and some validity by correlating with several physiologic variables reflecting habitual physical activity. The value of the YPAS, however, in accurately assessing low intensity activity remains to be established. PMID- 8492693 TI - Development of a submaximal treadmill jogging test for fit college-aged individuals. AB - The purpose of this study was to develop a single-stage submaximal treadmill jogging test for the estimation of maximal oxygen uptake (VO2max). VO2max was measured in 129 relatively fit individuals (males = 84, females = 45), 18-29 yr, using a maximal treadmill protocol (mean +/- SD; VO2max = 48.3 +/- 6.2 ml.kg-1 x min-1, range = 35.6 to 62.3 ml.kg-1 x min-1). The treadmill test required subjects to sustain a comfortable, submaximal jogging pace (4.3-7.5 mph; level grade) until a steady-state heart rate was achieved (approximately 3 min). To help ensure that a submaximal level of exertion was realized for the treadmill jogging test, treadmill speed and exercise HR criteria were established that restricted treadmill speed to < or = 7.5 mph for males and < or = 6.5 mph for females and steady-state exercise HR < or = 180 bpm. Multiple regression analysis (N = 66) to estimate VO2max from the treadmill jogging test yielded the following validation (V) model (r(adj) = 0.84, SEE = 3.2 ml.kg-1 x min-1): VO2max = 54.07 + 7.062 * GENDER (0 = female; 1 = male) - 0.1938 * WEIGHT (kg) + 4.47* SPEED (miles.h-1) - 0.1453 * HEART RATE (bpm). Cross-validation (CV) of the treadmill jogging test comparing observed and estimated VO2max (N = 63) resulted in r(adj) = 0.88, SEE = 3.1 ml.kg-1 x min-1. The results indicate that this submaximal single-stage treadmill jogging test based on multiple linear regression provides a valid and convenient method for estimating VO2max. PMID- 8492694 TI - Body composition analysis of female adolescent athletes: comparing six regression equations. AB - This study investigated whether meaningful differences occurred when percentage body fat (%BF) values were estimated for female adolescent athletes using six different regression equations found in the two of which were age-adjusted. Skinfold thickness (SF) and bioelectrical impedance analysis (BIA) measurements were taken prior to training and > or = 2 h postprandial on 29 gymnasts and 25 speed skaters who competed at a minimum of a provincial level. Mean ages were similar (14.3 +/- 1.6 yr, mean +/- SD, vs 14.3 +/- 1.5 yr); however, the speed skaters were taller (162.2 +/- 8.2 cm vs 154.0 +/- 5.0 cm, P < 0.001) and heavier (58.5 +/- 9.5 kg vs 46.0 +/- 7.9 kg, P < 0.001). Analysis of variance of %BF revealed a significant effect of sport (F(1,52) = 39.3, P < 0.001), with gymnasts having lower values. There was also a significant effect of regression equation (F(5,260) = 147.8, P < 0.001), and post-hoc comparisons revealed significant differences between almost all equations. Calculated %BF values ranged from 21.0 +/- 7.7% to 28.1 +/- 3.9% for speed skaters and from 10.3 +/- 5.3% to 22.8 +/- 3.7% for gymnasts. For both sports, the age-adjusted equations for SF and BIA produced the lowest and the highest %BF values, respectively. Our results indicate the need for caution when using field techniques to estimate %BF of female adolescent athletes. We suggest that an appropriate technique and regression equation for use with this group is the Jackson and Pollock quadratic equation for skinfolds, using Lohman's age-adjusted specific constants to correct for lower density of fat-free mass in youths. PMID- 8492695 TI - [Chronic bronchitis and efficiency of lung ventilation in workers of the "Zawadzkie" foundry]. AB - The aim of this study was to determine the influence of smoking habit and occupational exposure to air pollution on the prevalence of chronic bronchitis and lung function efficiency in foundry workers. MRC survey and spirographic measurements were performed in 917 men aged 18-62 years (mean age 38.6). In 455 men (49.6%), occupational exposure to air pollution significantly exceeded the permissible values. In 122 men (13.3%) the exposure was low. Chronic bronchitis was more than twice as frequent in smokers (27.3%) as in nonsmokers (11.0). Cessation of smoking led to an improvement in the symptoms of chronic bronchitis. Chronic bronchitis was slightly more frequent in highly exposed (25.5%) as compared with low-exposed workers (15.6%). Age-related lung function decline was significantly greater in smokers than in nonsmokers. Unlike chronic bronchitis, lung function was still lower after smoking cessation. Among highly exposed workers, age-related FVC and FEV1 declines were significantly larger in smokers than in non-smokers. PMID- 8492696 TI - [Methods for palestesiometric measurement in workers exposed to local vibration]. AB - The paper discusses methodology for the vibration perception measurement as well as specifies the mean values and standard deviation of the vibration perception threshold in people not exposed to vibration. The increase of the threshold level of vibration perception in chain-saw operators, chippers and grinders has also been analysed. PMID- 8492697 TI - [Evaluation of renal function based on cytologic examination of urine sediments in industrial workers employed in a Bydgosz conveyer belt plant "Pasamon" ]. AB - 215 healthy workers, aged 19-61, of Bydgoszcz industrial plant were examined. In some patients urine sediments contained pathological ingredients, which could be an early symptom of a urinary tract disease. No traits of neoplastic processes were found. PMID- 8492698 TI - [Cytoenzymatic examinations of peripheral blood granulocytes in overhaul workers of the chemical plant "Organika-Jaworzno" at Jaworzno]. AB - In order to evaluate the functions of granulocytes, cytochemical reactions to alkaline and acid phosphatases, beta-glucuronidase, myeloperoxidase and catalase were performed in leukocyte concentrate smears for 45 overhaul workers of a chemical plant producing pesticides. As compared to the control group of 24 unexposed healthy individuals living in the plant area, the alkaline phosphatase and catalase reactions were weaker; the leukocyte count was slightly elevated; the differential white blood cell count did not show any significant changes, only the percentage of monocytes was slightly reduced. The results of our studies can testify a slight impairment of leukocyte function in workers exposed to chemical pesticides. PMID- 8492699 TI - [Assessment of exposure to halothane in operating suites of selected hospitals and clinics]. AB - The paper presents a comparison of results of measuring air concentration of halothane, a drug widely used for inhalation narcosis. Air samples were taken directly from the operating theatres and analysed by GC. Our results confirm the ones obtained in other countries--among the whole medical staff the anaesthesiologists and surgeons bear the highest health risk. The findings of the study together with the results of an analysis of air conditioning and the methods of anaesthesia would indicate that the working conditions in operating suits should be improved. PMID- 8492700 TI - [Method of simultaneous determination of sulfuric acid and hydrochloric acid in the air of the workplace]. AB - The paper discusses a method for simultaneous determination of sulfuric and hydrochloric acid in the workplace atmosphere. The air samples were collected on the Whatman filter impregnated with 0.2 mol/l sodium carbonate solution. The acids were determined by the turbidimetric method: sulfuric acid with barium chloride and hydrochloric acid with silver nitrate. PMID- 8492701 TI - [Professional consciousness of dentists in occupational health care]. AB - The specific nature of activities of dentists employed in occupational health care (OHC) has often been questioned. At the same time, there is a general opinion that the status of OHC dentists is superior in respect of dental surgery equipment, room space, relations with patients, etc. Based on the results of the Polish episode of international comparative study on dental care effectiveness, an attempt was made to answer the question about the professional characteristics of dentists employed in OHC units. The study referred both to OHC dentists and those who work primarily in the public health service. It was assumed that the professional consciousness of the respondents would be reflected in their opinions on: 1. professional satisfaction, 2. compatibility of professional duties, 3. disadvantages of the profession, 4. prospects for hereditary continuation of the profession, 5. patient behaviour, 6. significance of preventive activities in dental health care, 7. dental health care in Poland. The results of the study indicate that there is some sense of professional distinctiveness among the OHC dentists. This can be traced to different technical, organizational and economic conditions under which that group of dentists performs their duties. PMID- 8492702 TI - [An analysis of causes of acute poisoning in Poland during 1989-1990]. AB - An analysis was carried out of the structure of acute poisonings, by various toxic agents and preparations, during the period 1989-1990, based on the data from regional centres of clinica toxicology. According to these data, suicidal attempts were the most frequent cause of poisonings. The prevailing agents of the poisonings included drugs, primarily sleep-inducing and psychotropic. Alcohols were placed secondly and the third place agents included gases, organic solvents, pesticides and mushrooms. PMID- 8492703 TI - [The effect of organic solvents on the inner ear]. AB - The paper is a literature review presenting different views and opinions on the effects of organic solvents on the vestibular and hearing organs. The analyzed reports indicate that organic solvents can produce central vestibular organ impairments as well as extra-cochlear high-frequency hearing loss. PMID- 8492704 TI - [Problems with certification of work capability for people with symptoms of functional and organic diseases of cerebral vessels]. AB - The problems of certifying work capability for people with the symptoms of functional and organic diseases of cerebral vessels were investigated basing on the documentation of 470 medical consultations performed at the Out-Patient Department of Occupational Diseases, the Institute of Occupational Medicine, Lodz, Poland. The certification was most difficult in people with angiogenic headache, symptoms of transient cerebral ischaemia and apoplexy with non intensive deficiency signs. The certification criteria most appropriate for that group of diseases were formulated. PMID- 8492705 TI - Hepatic regulation of pancreatic alpha-cell function. AB - The direct feedback regulation between the endocrine gland and its target organ is an expected biological relationship. However, such a phenomenon is far from being well established in the case of the endocrine pancreas and its major target organ, the liver, especially since plasma glucose has been established as the prime regulator. In this perspective, I have reexamined the feedback regulation between plasma glucose and glucagon secretion by the pancreatic alpha cell. Surprisingly, available data in the literature appear to document a frequent breakdown of this well-established interdependence between plasma glucose and pancreatic alpha cells, as reflected by a sustained elevation of plasma glucagon levels in several physiologic and pathologic states with concurrent euglycemia or hyperglycemia. Moreover, normal or low glucagon concentrations in the presence of fasting hypoglycemia in patients with insulinoma or non-islet cell tumors secreting insulin-like peptides and in patients with hepatic glycogen storage disorders may enhance our hypothesis that plasma glucose level may not be the major regulator of glucagon secretion. Extensive data in the literature show that hyperglucagonemic states are characterized by a unique metabolic environment, namely hepatic glycogen depletion. Similarly, hepatic glycogen stores are abundant in the presence of normal or low glucagon concentrations. These findings imply a distinct relationship between hepatic glycogen content and plasma glucagon level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492706 TI - Reduced postexercise recovery oxygen consumptions: an adaptive response in chronic energy deficiency? AB - Maximal aerobic capacity (VO2max) and oxygen consumption during recovery were measured in well-nourished control subjects (C) and compared with results from chronically energy-deficient (CED) subjects in the same age range. The absolute VO2max was lower in undernourished subjects (2.5 +/- 0.1 L/min [C] v 1.8 +/- 0.1 L/min [CED]; mean +/- SEM, P < .001); however, when expressed per kilogram fat free mass (FFM), the values were comparable. The total O2 debt was higher in the well-nourished group even when corrected for FFM differences (249.1 +/- 17.1 v 147.3 +/- 9.2 mL/kg FFM; P < .001). O2 consumption in the recovery period returned to baseline values rapidly and in a single phase in undernourished subjects. In contrast, a slow biphasic decline was observed in well-nourished control subjects. The postexercise recovery phase may be an important period during which energy-saving may occur in chronically undernourished human subjects. PMID- 8492707 TI - Body fat topography as an independent predictor of fatty liver. AB - Abdominal (truncal) fat distribution reflected by an elevated waist to hip ratio (WHR) predicts metabolic abnormalities such as diabetes and dyslipidemia as well as hypertension and stroke, all of which are associated with obesity. The pathogenesis is not known, although elevated splanchnic serum free fatty acid levels and reduced hepatic insulin clearance have been implicated. WHR and body fat (BF) by 40K-counting and 3H2O were measured before liver biopsy during antiobesity surgery in 68 severely obese women (body mass index [BMI], 48.9 +/- 1.1 SEM) and 15 men (BMI, 49.0 +/- 3.1) without histories of liver disease, diabetes, or hepatotoxic exposure. Biopsies were graded for fat content semiquantitatively (0 to 4+) by the hepatologist who was blinded to the patients' clinical characteristics. All 15 men had fatty infiltration (score, 2.5 +/- 0.3 v 1.4 +/- 0.1 in women; P < .001). The correlation between WHR and liver fat was .44 (P < .0005), while BF (-.16), weight (.15), or BMI (.04) did not correlate significantly with steatosis (all NS). As expected, percentage body fat (BF%) was greater in women than in men (40.3 +/- 0.8 kg v 33.9 +/- 2.0, P < .007), and accordingly liver fat was inversely related to BF% (r = -.32, P < .002). Steatosis was significantly greater in 14 men (2.5 +/- 0.3) than in 20 women (1.7 +/- 0.3, P < .04) matched for BF%. In multiple regression analysis R2 = .49, P < .0001), WHR and sex accounted for the variance in liver fat content without any further contribution from weight, BMI, BF, or BF%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492708 TI - Pancreastatin--a mediator in the islet-acinar axis? AB - Pancreastatin was isolated from porcine pancreas in 1986 and has been shown to inhibit insulin release and exocrine pancreatic secretion in vivo. In the isolated perfused rat pancreas, we investigated its effect on the exocrine pancreas and evaluated its indirect effects mediated via the islet-acinar axis. In the presence of 16.7 mmol/L glucose, 20 pmol/L, 200 pmol/L, and 2 nmol/L pancreastatin reduced insulin release but did not affect exocrine pancreatic secretion stimulated by cholecystokinin (CCK), secretin, or bombesin. Pancreastatin also failed to affect unstimulated exocrine pancreatic secretion. In the presence of 1.7 mmol/L glucose, 200 pmol/L and 2 nmol/L pancreastatin inhibited glucagon release and potentiated CCK-stimulated exocrine pancreatic secretion. Inhibition of glucagon release and augmentation of exocrine pancreatic secretion may be independent phenomena, but they could be linked by the islet acinar axis. Thus we speculate that a pancreastatin-induced inhibition of glucagon release may indirectly have caused augmentation of exocrine pancreatic secretion. PMID- 8492709 TI - Hypothyroid-like regulation of the pituitary-thyroid axis in stable human immunodeficiency virus infection. AB - Thyroid function and regulation were studied in 14 consecutive male outpatients with asymptomatic human immunodeficiency virus (HIV) infection (CDC II/III, n = 8) or AIDS (CDC IV, n = 6) who were free of concomitant infections and hepatic dysfunction, and in eight healthy, age- and weight-matched male controls. Blood was sampled every 10 minutes over 24 hours for measurement of thyrotropin (TSH). Thereafter, thyroid hormones and TSH responsiveness to thyrotropin-releasing hormone (TRH) were measured. Triiodothyronine (T3) and thyroxine (T4) did not differ between HIV-infected patients and controls, but HIV patients had lower thyroid hormone-binding index ([THBI] HIV patients, 1.01 +/- 0.02; controls, 1.11 +/- 0.03; P < .02), free thyroxine (FT4) index (94 +/- 3 v 110 +/- 4, P < .01), FT4 (11.8 +/- 0.4 v 14.3 +/- 0.4 pmol/L, P < .01), and reverse triiodothyronine (rT3) values (0.18 +/- 0.01 v 0.26 +/- 0.02 nmol/L, P < .001) and higher thyroxine-binding globulin ([TBG] 20 +/- 1 v 16 +/- 1 mg/L, P < .02) values. Mean 24-hour TSH levels were increased in HIV patients (2.39 +/- 0.33 v 1.44 +/- 0.16 mU/L, P < .05), associated with increased mean TSH pulse amplitude and TSH responsiveness to TRH. No differences were observed between asymptomatic HIV seropositive and AIDS patients. In conclusion, there is a hypothyroid-like regulation of the pituitary-thyroid axis in stable HIV infection, which differs distinctly from the euthyroid sick syndrome in non-HIV-nonthyroidal illnesses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492710 TI - The relationship between the phospholipid fatty acid composition of red blood cells, plasma lipids, and apolipoproteins. AB - This study examined the relationship between the fatty acid composition of red blood cell phospholipids and lipid markers of atherosclerotic risk in an urban male population aged 45 to 66 years. There was a surprisingly significant positive association between the docosahexaenoic acid ([DHA] 22:6n-3) content of erythrocyte phospholipids and the following risk markers: plasma cholesterol (P < .01), low-density lipoprotein (LDL) cholesterol (P < .01), apolipoprotein (apo) B (P < .05), and apo B-containing lipoprotein particles (P < .05) recognized by a monoclonal antibody (LpBL3). On the other hand, phospholipid alpha-linolenate was positively correlated with apo A-I and high-density lipoprotein (HDL) cholesterol levels (P < .05), while arachidonate showed an inverse relationship with plasma cholesterol (P < .05). There was a negative association between palmitoleic acid and apo B (P < .01) and LpBL3 (P < .001); the latter showed a negative association with stearic acid (P < .001). These interesting findings emphasize the beneficial effect on atherosclerotic risk markers of dietary n-6 polyunsaturated and monounsaturated fatty acids, and suggest that long-chain n-3 polyunsaturated fatty acids (DHA) could have an adverse effect on some of the lipid risk markers. PMID- 8492711 TI - Distribution of adipose tissue and muscle mass in alcoholic men. AB - An elevated waist to hip ratio (WHR) has been found to be a predictor for several prevalent diseases. To examine the potential role of alcohol in the elevation of WHR, established alcoholic men without severe liver damage who were in adequate nutritional condition were compared with organized teetotalers matched for age, height, and body weight; the groups had similar total body fat content and lean body mass. Computed tomographic (CT) measurements at thigh and trunk levels showed a significant increase in the visceral adipose tissue (AT) areas and a slight decrease of muscle areas in the gluteal and femoral regions of the alcoholics. The alcoholic men had 48% of their AT areas of trunk scans localized retroperitoneally and intraperitoneally compared with 38% for the teetotalers (P < .01). The difference seemed to be more marked for retroperitoneal than for intraperitoneal AT (97 v 60 cm2, P < .01). The elevated visceral AT areas seemed to be independent of smoking. It was concluded that the increased WHR of alcoholics may include not only changes in AT, but also in muscle tissue distribution. PMID- 8492712 TI - Coordinate regulation of triacylglycerol synthesis and glucose transport by acylation-stimulating protein. AB - Acylation-stimulating protein (ASP) is the most potent recognized stimulant of triacylglycerol synthesis in human adipocytes. However, its mechanism(s) of action have not yet been elucidated in detail. The present study examines the effects of ASP on membrane transport of glucose and fatty acids in cultured human skin fibroblasts. The data demonstrate that ASP stimulated carrier-mediated glucose transport in a time- and concentration-dependent manner, an effect that was greater than and independent of that observed with insulin. ASP increased the Vmax for glucose transport with no change in the transport Km, suggesting that ASP might result in increased sugar transporters in the plasma membrane. This finding was supported by quantitative Western blot analyses using a monoclonal antibody (G3) that demonstrated an increase in the plasma membrane content of the glucose transporter (Glut 1) with a concomitant decrease in the glucose transporter content of an intracellular membrane fraction. By contrast, ASP had no effect on specific membrane transport of fatty acids. Maximal effects of ASP on triacylglycerol synthesis were demonstrated at saturating levels of both glucose and oleate. Comparable stimulation by ASP in the absence of glucose (with or without pyruvate) was also demonstrated, although the absolute rates of triacylglycerol synthesis were substantially lower. Finally, it was shown that ASP increased the apparent Vmax for triglyceride synthesis without changing its Km. Since ASP will act in the absence of extracellular glucose, ASP must have additional actions, independent of its effect on specific membrane transport of glucose by which it accelerates intracellular triglyceride synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492713 TI - Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy. AB - There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% +/- 1.8% (mean +/- SEM) of ideal body weight (IBW), and following partial restoration were 84.3% +/- 1.4%. Body weights in normal controls were 96.3% +/- 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls (P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492714 TI - Effects of acute hypercarnitinemia during increased fatty substrate oxidation in man. AB - To test whether carnitine availability is rate-limiting for fat oxidation under conditions of augmented oxidative use of fatty substrates, two series of studies were performed. In study no. 1, L-carnitine (1 g + 0.5 g/h intravenously [i.v.]) or saline was given to eight volunteers during a 4-hour infusion of a 10% triglyceride emulsion, thereby increasing plasma free-carnitine levels from 38 +/ 4 to 415 +/- 55 mumol/L. Fat infusion increased plasma triglyceride levels (80%) and lipid oxidation (30%), and decreased (28%) carbohydrate oxidation (as measured by indirect calorimetry); hypercarnitinemia had no influence on these responses. In study no. 2 in 12 healthy subjects a bolus of L-carnitine (3 g) or saline was administered 40 minutes before aerobic exercise (bicycling for 40 minutes at 60 W), followed by 2 minutes of anaerobic exercise (250 W) and 50 minutes of recovery. Oxygen consumption (VO2), increased to 18.3 +/- 0.7 mL.min-1 x kg-1 during aerobic exercise, reached a maximum of 46.0 +/- 0.8 mL.min-1 x kg-1 during the anaerobic bout, and returned to baseline within a few minutes, with no difference between control and carnitine. At virtually identical mean energy expenditure rates (196 +/- 7 v 197 +/- 7 J.min-1 x kg-1, saline v carnitine), after carnitine administration the entire exercise protocol was sustained by a lower mean carbohydrate oxidation rate (42.1 +/- 3.6 v 36.5 +/- 2.3 mumol.min-1 x kg-1, P < .03) and a higher mean lipid oxidation rate (6.7 +/- 1.0 v 8.3 +/- 0.7 mumol.min-1 x kg-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492715 TI - Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids. AB - Plasma nonesterified fatty acid (NEFA) levels are increased in the insulin stimulated state in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to the decrease in peripheral and hepatic insulin sensitivity. To test this hypothesis and to avoid the confounding effect of obesity, we examined the effect of decreasing plasma NEFA levels on peripheral and total glucose metabolism in eight non-obese, NIDDM patients. Each received 250 mg Acipimox (a nicotinic acid analogue) or placebo at 0 and 120 minutes on separate occasions. [6,6-2H2]-glucose (0 to 300 minutes) and insulin (120 to 300 minutes) were infused in each study, and isoglycemia was maintained. Plasma NEFA levels (140 +/ 30 v 600 +/- 70 mumol/L [SEM]; P < .001) and forearm NEFA uptake measured with [1-14C]-palmitate (+93 +/- 21 v +313 +/- 42 nmol x 100 mL forearm-1; P < .001) were decreased with acipimox during the basal period (90 to 120 minutes), with no change in forearm glucose uptake (+334 +/- 80 and +330 +/- 60 nmol x 100 mL forearm-1 x min-1) and hepatic glucose output ([HGO] 13.6 +/- 0.9 and 13.4 +/- 0.7 mumol.kg-1 x min-1). Serum insulin (256 +/- 12 and 266 +/- 18 pmol/L) and plasma glucose (9.5 +/- 0.6 and 9.4 +/- 0.5 mmol/L) levels were comparable during the clamp period (270 to 300 minutes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492716 TI - Effects of cholesterol uptake from high-density lipoprotein on bile secretion and 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in perfused rat liver. AB - Small aliquots of rat high-density lipoproteins (HDL) (388 +/- 67 nmol lipoprotein cholesterol) were labeled with [14C]cholesterol and administered as a bolus to perfused rat livers. Bile and perfusate samples were collected for 2 hours at 30-minute intervals. After perfusion, both the microsomes and lipid extracts were prepared from the livers. Lipid composition was examined in both liver and microsomes, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was evaluated in microsomes. Basal values of bile flow, lipid composition, and enzyme activity were evaluated using livers in which perfusion was discontinued before injecting the lipoprotein. In some experiments, the effect of perfusion per se was assessed by infusing saline instead of lipoprotein. After 10 minutes of lipoprotein perfusion, 50% of cholesterol administered was taken up by the perfused liver. During infusion, transient but significant increases in both bile flow and bile steroid secretion were observed. Cholesterol administration, even if rapid, represented less than 0.4% of total liver cholesterol content. However, this was enough to significantly increase the cholesterol to phospholipid (CH/PL) molar ratio in liver microsomes and at the same time decrease HMG-CoA reductase activity. In conclusion, the main response of the perfused liver to HDL cholesterol infusion is a reduced activity of the rate-limiting enzyme in cholesterol biosynthesis, due to the shift in the microsomal CH/PL molar ratio. A small proportion of the infused cholesterol enters bile as cholesterol and bile salts. PMID- 8492717 TI - Insulin-induced activation of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats. AB - The pyruvate dehydrogenase (PDH) complex undergoes reversible phosphorylation catalyzed by a PDH kinase (inactivating) and a PDH phosphatase (activating). In skeletal muscle, a decreased proportion of active PDH (PDHa) complex limits glucose oxidation in insulin-deficient states. The time-course for reactivation of the PDH complex by insulin in skeletal muscle of diabetic rats is important to understanding the potential mode of the action of insulin in regulating glucose metabolism. A single injection of insulin (1 U/kg) completely reversed the effects of alloxan-diabetes on PDHa activity within 1 hour. The normalization of the effects of diabetes on PDHa activity by insulin was maintained for a minimum of 6 hours. The increase in PDHa activity occurred before an insulin-induced decrease in plasma free fatty acids levels, demonstrating a dissociation between the antilipolytic effects of insulin and its ability to activate the PDH complex. PDH kinase activity was not normalized to control values following a single injection of insulin. Therefore, acute (1 to 6 hours) insulin-mediated activation of the PDH complex does not result from a decrease in PDH kinase activity. However, longer-term insulin therapy (1 U/kg body weight; twice daily) restored both PDHa and PDH kinase activities. The results are consistent with the hypothesis that activation of the PDH complex immediately following insulin administration is not mediated by a decreased PDH kinase activity. However, with daily insulin therapy in diabetes, activation of the PDH complex results from decreased PDH kinase activity. PMID- 8492718 TI - Sulfonylureas activate glycogen phosphorylase and increase cytosolic free-Ca2+ levels in isolated rat hepatocytes. AB - Without causing significant changes in cellular levels of cyclic adenosine monophosphate (cAMP), the addition of either glibenclamide or gliquidone to isolated rat hepatocytes caused a transient dose- and Ca(2+)-dependent activation of glycogen phosphorylase. The calculated concentrations corresponding to half maximal activation were 5 and 2 mumol/L, respectively. In connection with this, it was observed that glibenclamide provoked a dose-dependent increase in cytosolic free-calcium concentration ([Ca2+]i) in Fura-2-loaded hepatocytes. Moreover, the presence of glibenclamide in the incubation medium accelerated the rate of Ca2+ uptake by Ca(2+)-depleted hepatocytes. These findings suggest that an increase in [Ca2+]i could mediate some of the effects of sulfonylureas in liver metabolism. PMID- 8492719 TI - Effect of growth hormone deficiency on hormonal control of hepatic glycogenolysis in hypophysectomized rat. AB - The present study was designed to investigate the hormonal regulation of rat liver glycogenolysis in growth hormone (GH) deficiency. To this end, hepatocytes were isolated from control, GH-deprived (hypophysectomized and treated with triiodothyronine [T3] and corticotropin), and 7-day GH-supplemented fed rats and incubated with glucagon and alpha 1-adrenergic agonist (phenylephrine) to measure the hormonal activation of both glycogen phosphorylase and glucose production from glycogen stores. GH deficiency induces a combined decrease of 50% of the glycogen content, the activity of glucose-6-phosphatase, and the maximal hormone induced glycogen phosphorylase activity. Daily GH injections restore the levels of both glycogen phosphorylase and glucose-6-phosphatase. These enzymatic inductions occur without normalization of insulinemia. Despite the reduced levels of key enzymes of glycogenolysis, the stimulation of glucose production from glycogen in response to glucagon and phenylephrine is not modified in GH-deprived rats. An increase in the intrinsic activity of one or both of the enzymatic steps is postulated to compensate for the lower levels of enzymes, as indicated by the slopes of the correlation between glucose production and phosphorylase a activity (107 and 216 nmol glucose produced/min/U phosphorylase a [P < .001] in control and GH-deprived rats, respectively). GH replacement enhances maximal phosphorylase activity and brings the correlation toward the control value (slope, 128 nmol glucose produced/min/U phosphorylase a). Our findings demonstrate that glycogenolysis in hepatocytes isolated from GH-deprived rats is normal, despite a reduction of glycogen phosphorylase and glucose-6-phosphatase activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492720 TI - Serum testosterone fractions in women: normal and abnormal clinical states. AB - The potential usefulness of determining serum testosterone (T) fractions in women, ie, sex hormone-binding globulin (SHBG)-bound T, albumin-bound T (Alb-T), and free T (FT) fractions, was explored in a variety of clinical situations. Serum T, SHBG, and albumin concentrations were measured by standardized methods and using binding constants of T to SHBG and albumin, we calculated serum T fractions, which agreed remarkably with measured values of SHBG-T and nonbound T. Serum T levels did not change in normal women examined during the follicular and luteal phases of the menstrual cycle, but SHBG levels were elevated in the luteal phase, changing the distribution of T, with increased SHBG-T and less T distributed to other fractions. Women taking oral contraceptives had decreased serum T levels, but use of androgen-like oral contraceptives decreased SHBG levels and T distribution to this binding protein, whereas use of non-androgen like oral contraceptives increased SHBG levels, resulting in the expected shift of T fractions. Women receiving phenytoin for seizure disorders and women with Graves' disease exhibited increased SHBG levels with concomitant increased SHBG-T and decreased distribution of T to nonbound fractions. Women with hirsutism exhibited decreased SHBG levels irrespective of total serum T levels, and the T/SHBG ratio was elevated in this population. However, of interest were women with morbid obesity (nonhirsute) who had similar low levels of SHBG and T/SHBG ratios that were indistinguishable from those of hirsute women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492721 TI - Acetate-induced changes of adenine nucleotide levels in rat liver. AB - The changes in adenine nucleotide concentration induced by acetate were investigated in rat liver in situ and in isolated rat hepatocytes. Adenosine monophosphate (AMP) concentration increased approximately threefold within 15 minutes after intraperitoneal injection of sodium acetate. A small but significant decrease in adenosine triphosphate (ATP) concentration also occurred. Consequently, the ATP/AMP ratio decreased from approximately 14 (the value found in control or sodium chloride-injected rats) to approximately 3 (the value found in sodium acetate-injected rats). Adenosine diphosphate (ADP) concentration increased slightly, but this was statistically nonsignificant. Total adenine nucleotide concentrations after acetate injection remained essentially the same as those in control rats. Adenylate energy charge decreased after acetate administration. No significant changes in nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) concentrations were found after sodium acetate injection. Similar patterns of changes in adenine nucleotide concentrations were found in isolated rat hepatocytes incubated in the presence of acetate. These data indicate that acetate, which appears in human blood either during hemodialysis with acetate-containing solution or after ethanol consumption, may alter energy equilibrium of adenine nucleotides in the liver. This is due to the conversion of ATP to AMP in the course of acetate to acetyl coenzyme A (CoA) activation. It is therefore possible that accelerated ATP turnover in the liver may contribute both to the "intolerance to acetate" in patients subjected to dialysis with the sodium acetate-containing solution and to the pathogenesis of gout associated with excessive ethanol consumption. PMID- 8492722 TI - The effect of oral casein on hepatic glycogen metabolism in fasted rats. AB - Casein hydrolysate administration to fasted rats resulted in a biphasic response of glycogen synthase. Fifteen minutes after the protein meal, synthase R (active form) was increased. This was associated with a transient increase in hepatic glucose and glucose-6-phosphate (G6P) concentrations. Both glucose and G6P are known to stimulate synthase phosphatase activity, which would result in activation of synthase. Portal plasma insulin concentration was directly related to the amount of synthase R present. By 1 hour after the meal, synthase R activity was decreased compared with the control activity. Hepatic glycogen concentration was variable during the first 30 minutes after the meal, and then decreased progressively. Portal plasma glucagon concentration and phosphorylase a activity were elevated at all time points. The data suggest that the increased portal plasma glucagon concentration is the major hormonal signal for glycogen metabolism during the second hour following a pure protein meal. However, during the first 30 minutes glycogenolysis is attenuated, perhaps due to the transient increase in insulin and an increased intracellular G6P concentration. PMID- 8492723 TI - Hypersecretion of amylin from the perfused pancreas of genetically obese (fa/fa) rats and its alteration with aging. AB - To evaluate the relationship between the development of obesity and the hypersecretion of amylin by the pancreas, we examined the effects of 16.7 mmol/L glucose and 10 mmol/L arginine on the secretion of amylin and insulin by isolated perfused pancreata from genetically obese (fa/fa) and lean (Fa/?) Zucker rats at 9, 18, and 54 weeks of age. Concentrations of amylin and insulin in the effluent were measured by radioimmunoassay (RIA). Pancreata of obese rats secreted greater amounts of amylin in response to 16.7 mmol/L glucose and 10 mmol/L arginine than did those of lean rats at all ages. The hypersecretion of amylin by obese rats was particularly marked at 18 weeks of age, when they showed the most rapid increase in body fat mass. This hypersecretion became obscure at 54 weeks of age, when obese rats showed the maximum body weight. The pattern of amylin release resembled that of insulin in all groups. However, the relative amount of amylin to insulin secreted following stimulation with 16.7 mmol/L glucose and 10 mmol/L arginine in obese rats exceeded that in lean rats at all ages. Differences in the secreted amylin to insulin molar ratios between obese and lean rats were significant when pancreata were stimulated with glucose at 18 weeks (obese, 1.23% +/- 0.05%; lean, 0.99% +/- 0.04%; P < .01), glucose at 54 weeks (P < .01), and arginine at 54 weeks (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492724 TI - Evidence for a relationship between free radicals and insulin action in the elderly. AB - In forty healthy subjects with normal glucose tolerance divided by age into four groups (group A, subjects with mean age < 25 years [n = 10]; group B, subjects with mean age < 40 years [n = 9]; group C, subjects with mean age < 60 years [n = 11]; group D, subjects with mean age > 75 years [n = 10]) and were matched for body mass index (BMI), lean body mass (LBM), mean arterial blood pressure, and sedentary life style, we determined the plasma O2- production, reduced to oxidized glutathione level ratio (GSH/GSSG), and plasma membrane microviscosity. Euglycemic hyperinsulinemic (1 mU/kg.min-1 for 120 minutes) glucose clamp with simultaneous D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation. In the oldest group of subjects, a significant increase in plasma O2-production and membrane microviscosity associated with a significative reduction in glucose disappearance rate (Rd), total body glucose disposal (TBGD), and nonoxidative glucose metabolism was found. In group D subjects (n = 10), all of these changes were correlated with one another. In a multiple regression analysis of the pooled data from all study subjects (n = 40), only plasma O2- production levels displayed a statistically significant relation with TBGD and nonoxidative glucose metabolism. In conclusion, in aged patients a significant relationship between free radical production and insulin action seems to exist. PMID- 8492725 TI - Arginine blocks the inhibitory effect of hydrocortisone on circulating growth hormone levels in patients with acromegaly. AB - In patients with acromegaly, circulating growth hormone (GH) levels and GH responses to GH-releasing hormone (GHRH) are decreased by long-term administration of pharmacological doses of glucocorticoids. The aim of our study was to investigate the acute effects of intravenous (i.v.) infusion of hydrocortisone combined either with saline or arginine infusion on circulating GH levels in acromegaly. We studied five adult patients with acromegaly, two men and three women aged 54.6 +/- 4 years having a body mass index of 25.9 +/- 1.2 kg/m2. On two randomized occasions, patients underwent a bolus i.v. injection of 100 mg hydrocortisone succinate at time 0 followed by a 120-minute i.v. infusion of 250 mg hydrocortisone in 250 mL saline, combined with a 90-minute (from -15 to 75 minutes) i.v. infusion of (1) 60 g arginine hydrochloride in 200 mL saline, or (2) 200 mL saline. In all of the acromegalic patients during the infusion of hydrocortisone alone, serum GH levels clearly decreased (nadir range, 26.4% to 68.1%) with respect to GH levels before hydrocortisone administration (mean of time -15 and 0, basal level), with a nadir between 90 and 180 minutes after the beginning of the infusion. After arginine pretreatment, GH levels were significantly enhanced compared with levels attained with hydrocortisone saline, and they were also significantly increased (peak, 167.5% +/- 27.7%) with respect to basal levels. Our data show that arginine blocks the inhibitory effect of acute and sustained hypercortisolism on circulating GH levels in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492726 TI - The use of stereotypes in the provision of midwifery care. PMID- 8492727 TI - HIV antibody testing in the antenatal clinic. AB - With the increase in human immunodeficiency virus (HIV) seroprevalence amongst women attending the antenatal clinic in the UK it is essential that women are adequately prepared to make an informed decision about being tested for HIV and to receive the result of such testing. This paper discusses the purpose of testing, the necessity of pre-test counselling, its content and the practical implications of providing it. Guidelines for the content of a pre-test counselling session are outlined with particular reference to issues pertinent to the pregnant woman: vertical transmission, the effect of pregnancy on disease progression, the effect of HIV on pregnancy, the prognosis for an infected child and so on. PMID- 8492728 TI - A diagnostic model for the evaluation of childbirth and parenting education. AB - A research study examined current issues in childbirth and parenting education in the Australian Capital Territory (ACT). In this article continuing official scepticism about the effectiveness of these programmes, despite evidence of consumer satisfaction and commitment from service providers, is noted. A critical review of the literature reveals the absence of a systematic framework for evaluation of childbirth education programmes. A framework which incorporates a methodology for health education planning and evaluation in a management context is proposed as a means of overcoming this deficiency. This framework enables a focus on the effectiveness of these health services from the perspective of both clients and providers, and identification of strategic measures for improving programme delivery and educational outcomes. PMID- 8492729 TI - Neonatal hypoglycaemia--blood glucose monitoring and baby feeding. AB - Recent concerns regarding neurological sequelae of neonatal hypoglycaemia have raised the question of whether demand breast feeding may increase the risks of neonatal hypoglycaemia and neurological handicap. In this review article neonatal hypoglycaemia is defined, monitoring of babies for this condition is discussed and implications for baby feeding practices are stated. PMID- 8492730 TI - The development of a neonatal stool colour comparator. AB - The policies which exist to monitor the passage of neonatal stool vary between and within hospitals. When stool colour is required, the recorded observations are invariably subjective opinions and as such are largely unreliable. The development of a stool colour comparator allowed an objective test to be used by professional staff and mothers. This facilitated data collection for a study which sought to determine, among other factors, the transition time of meconium through to the yellow stool of the milk-fed baby, during the early neonatal period. The transition time of the meconium is indicative of gastrointestinal activity in the newborn and midwives are able to correlate accurately documented changes in stool colour with the baby's daily weight loss to assess the quality and/or adequacy of early infant feeding particularly breast feeding. The stool colour comparator is used in postnatal wards at Ninewells Hospital, Dundee by mothers and midwives and the numerical coding has replaced the previously used subjective abbreviations Mec (Meconium), Ch (Changing) and Y (Yellow). PMID- 8492731 TI - Stereotypes of women of Asian descent in midwifery: some evidence. AB - The subject of this paper is part of a larger study which investigated the delivery of maternity care to women of South Asian descent in Britain (Bowler, 1990). An ethnographic approach was used and the main method of data collection was non-participant observation in antenatal clinics, labour and postnatal wards in a teaching hospital maternity unit. These observations were supported by data from interviews with midwives. It was found that the midwives commonly use stereotypes of women in order to help them to provide care. These stereotypes are particularly likely to be used in situations where the midwife has difficulty (through pressure of time or other circumstances) in getting to know an individual woman. The stereotype of women of Asian descent contained four main themes: communication problems; failure to comply with care and service abuse; making a fuss about nothing; a lack of normal maternal instinct. Reasons for stereotyping are explored. Effects on service provision in the areas of family planning and breast feeding are highlighted. PMID- 8492732 TI - [Socioeconomic status and coronary disease: theories, research methods, epidemiological evidence and the results of Italian studies]. AB - This review covers the most important theoretic contributions and results of epidemiological research on the relationship between socio-economic status (SES) and coronary heart disease (CHD). Two major approaches have been identified: those of the British and American schools. In spite of differences in method, most of published contributions have shown social inequalities in the outcome of most degenerative disorders. Similar patterns have been detected for the CHD: the time trend declines documented in recent years in most industrialized countries has not filled in the gap of SES difference in the incidence and mortality for CHD, which even seems to have increased in the lower social classes. Moreover, an apparent paradox has been described: even though CHD is typical of welfare societies, its impact is higher in the lower social classes. Recent results of Italian studies are reported which investigated the relationship between CHD risk factors and SES in representative samples. The findings suggest the presence, in Italy, too, of social discrepancies in the prevalence of major risk factors, in both gender groups. This should be taken in consideration when preventive programmes are planned in populations or in work settings. PMID- 8492733 TI - [The contribution of science to health promotion in the workplace]. AB - An imposing amount of knowledge has been produced during the course of three hundred years of research in the field of occupational medicine and in other specialisations that in the last fifty years developed as branches of this discipline (industrial hygiene, industrial toxicology, respiratory physiopathology, etc). Part of this scientific heritage has been used to the full to plan and carry out prevention measures that have led to improved working conditions in many sectors of industry. Examples are the successes obtained in the prevention of pneumoconioses, aplastic anaemia and leukemia due to benzene, cancer caused by aromatic amines, and diseases occurring in pesticide users and consumers of agricultural products treated with such products. More recently, through original research programmes, with particular reference to the "Clinica del Lavoro" of Milan, a theoretical revision was made of the conception and method for analysing the relationship between organised work and health, resulting in an organic arrangement of the variables and procedures for the analysis of working conditions for the purposes of prevention. Other ways and areas where scientific bio-medical knowledge can be used are: a) planning of prevention measures on a vast social scale; b) variables and indicators for planning and assessing services designed for diagnosis and prevention of occupational risks and diseases; c) development of training programmes. In spite of these positive results, European Community statistics show that still too many occupational accidents and work-related diseases occur all over the world, especially in the developing countries, because the amount of scientific knowledge used is still much smaller than what is already available. The causes of this situation are many, among which those of a cultural nature. The author proposes the setting up of an "International Network for the History of Occupational and Environmental Prevention", and furnishes a detailed illustration of the aims and foreseeable initial actions. PMID- 8492734 TI - Cohort study of mortality among farmers and agricultural workers. AB - A cohort study was made of the mortality experience of 1701 male and 426 female farm workers (Aprilia, Italy) during the period 1972-1988. A low overall mortality was found due mainly to a decreased risk of circulatory diseases and respiratory conditions. Also, the overall cancer mortality was reduced (SMR = 0.88 for males and 0.58 for females). No statistically significant excesses were observed in cancer mortality, but there was an evident tendency towards an increased risk of gastric cancer (0 = 23, SMR = 1.24), renal cancer (0 = 5, SMR = 2.12), skin cancer (0 = 2, SMR = 1.67) and leukemia (0 = 6, SMR = 1.54), mainly of the myeloid type. Finally, 41 lung cancer cases were observed against 40.12 expected. Under 65 years excess deaths were found for all cancer sites investigated except cancer of the lymphatic and hemopoietic tissues. Since farmers usually have a low lung cancer rate, the increased mortality in the young age group (0 = 24, SMR = 1.28) and also the excess of kidney cancer (0 = 4, SMR = 3.67), although not statistically significant, deserve consideration in relation to past exposure to pesticides, especially DDT, in this population. PMID- 8492735 TI - [Dosage indicators in farm workers exposed to mancozeb]. AB - A study was performed on a group of farm workers exposed to mancozeb to validate dose indicators. Two indirect methods have been employed to monitor the air dispersed mancozeb in the working environment (average concentration 57.2 micrograms/Nm3): carbon disulfide and manganese dosage. The latter proved to be more applicable. To assess skin contamination, the concentration of mancozeb was measured on pads placed on work overalls and in the liquid employed to wash workers' hands. Average concentrations of 0.86 microgram/cm2 and 641 micrograms respectively were obtained. A good correlation between mancozeb concentration on pads and in the air was found. Urinary ethylenethiourea (ETU) and manganese measured before and after a three day exposure were selected as indicators for internal dose. In all cases except three (2.9-2.3 and 4.4 mg/g creat.) ETU was below the sensitivity limit of the method employed. Urinary manganese increased from a mean of 0.32 microgram/g creat. to a mean of 0.53 microgram/g creat. after the exposure. The correlation with environmental data was r = 0.667. PMID- 8492736 TI - [Occupational Raynaud's phenomenon in a dentist: a case report]. AB - After more than 39 years of practice, a dentist showed Raynaud's phenomenon of the hand exposed to vibrations generated by dental instruments. Other possible occupational, pharmacological and systemic disease factors that could cause Raynaud's phenomenon were excluded. Since it has been reported in the literature that dentists and dental technicians could exceed the permissible limits for vibrations, an occupational etiology of this case is suggested on the basis of logical reasoning. PMID- 8492737 TI - [The measurement of a benzene metabolite, urinary S-phenylmercapturic acid (S PMA), in man by HPLC]. AB - Benzene is a widely used solvent, currently present in the industrial environment at concentrations in the order of ppm. A valid method of biological monitoring that is easy to perform is needed for assessing occupational exposures. Benzene is metabolized in the body by microsomal cytochrome P-450 mono-oxygenase system into benzene epoxide. Benzene epoxide is metabolized along three different pathways which end in the excretion of trans, trans muconic acid, S-phenyl mercapturic (S-PMA) and different phenols. A new method has been developed to evaluate urinary S-PMA of subjects exposed to benzene. Human urine is acidified with HCl to PH 1 and passed through a Sep-Pak C18 cartridge. The cartridges are washed with diluted HCl and a mixture of water/methanol/acetic acid and then eluted with acidified chloroform. The eluate is dried and reconstituted with a buffer phosphate, then passed through an anionic exchange cartridge (SAX) which is washed with diluted buffer and diluted HCl. S-PMA is recovered by eluting with concentrated buffer and is transformed into S-phenyl-cysteine. Finally, S-phenyl cysteine is detected by HPLC connected with a fluorescence detector (wavelengths: excitation 330 nm, emission 440 nm) after derivatization with o-phthalaldehyde (OPA) and 2-mercapto-ethanol (MCE). The detection limit of the method is about 0.5 micrograms/l, the recovery of S-PMA is 90.0% and the variation coefficient is 3.8%. The method was checked on urine samples of 8 male non-smokers and 10 smokers: median values of 1.3 and 9.2 micrograms/g creatinine respectively of S PMA were obtained. A further analysis on urine samples of 66 occupationally exposed workers (smokers and non-smokers) revealed a median value of S-PMA of 46.6 micrograms/g creatinine, compared with a median environmental benzene exposure of 1.99 mg/m3. These results suggest that S-PMA can be regarded in the future as a useful indicator for monitoring individual and collective low-level benzene exposure. PMID- 8492738 TI - [The biological monitoring of occupational exposure to anesthetic gas and vapors: the determination of nitrogen protoxide, halothane and isoflurane in the urine]. AB - A gas-chromatographic method has been developed for measuring urinary nitrous oxide, halothane and isoflurane concentrations. A volume of head-space gases obtained from biological samples is analyzed by ECD-GC on a steel column (2 mm ID) serially packed with Porapak Q (1.2 m) and MS-5A (0.30 m), operated at 160 degrees C. The detection limit (ranging from 0.03 micrograms/l for halothane to 1 microgram/l for nitrous oxide), between-day precision (CV < 6%) and working linear range (up to 100 micrograms/l for halothane and 2000 micrograms/l for nitrous oxide) were determined. A two-year experience in biological monitoring of occupationally exposed surgical staff with the proposed method is reported and confounding factors are discussed. The method is easy to perform, free from interferences and suitable for use in routine analysis in toxicological laboratories. PMID- 8492739 TI - [Exposure to radio frequencies can induce femoral necrosis?]. PMID- 8492740 TI - Microfibrillar assemblies of foetal bovine skin. Developmental expression and relative abundance of type VI collagen and fibrillin. AB - Intact type VI collagen microfibrils and fibrillin-containing microfibrils were isolated from foetal bovine skin and investigated immunochemically and ultrastructurally. Substantial variations were detected in the abundance and macromolecular assembly of these structures at progressive stages of gestation. Microfibrils of collagen VI were increasingly abundant in skin through foetal development from late first trimester to term. The pattern of expression of fibrillin-containing microfibrils in foetal skin differed from that of collagen VI. Fibrillin-containing microfibrils were particularly sparse in first trimester skin, and present only as short assemblies. However, by early second trimester there had been a sharp increase in the abundance and length of these fibrillin containing microfibrils. These observations are consistent with early second trimester being a key phase of fibrillin assembly. In the third trimester, fibrillin-containing microfibrils were frequently isolated in association with amorphous material. This information on the pattern of expression and assembly of collagen VI microfibrils and fibrillin-containing microfibrils in foetal skin implies temporally and functionally distinct contributions of these two components to the establishment of the fibrous dermal matrix. PMID- 8492741 TI - Developmental expression of osteopontin (OPN) mRNA in rat tissues: evidence for a role for OPN in bone formation and resorption. AB - Osteopontin (OPN) is a 34-kDa, highly-phosphorylated glycoprotein with cell attachment properties that is a prominent constituent of the bone matrix. To aid in elucidating the function of this protein we have studied the cellular expression of OPN mRNA during the formation, growth and maturation of rat calvarial (membranous) and tibial (endochondral) bone. From Northern hybridization analysis OPN expression was demonstrated in the kidney and gravid uterus as well as in bone tissues. Compared to collagen, the expression of OPN was low in early bone formation but increased subsequently and reached peak levels in 14-day-old bone. However, both the collagen and OPN mRNAs decreased markedly thereafter and remained low in young adult bone. From in situ hybridization studies using a [35S]-labelled rat OPN cRNA probe, OPN mRNA was localized to osteoblastic cells in newly-forming calvariae, jaw bones, and in the metaphyseal and periosteal bone of the tibia. In contrast to bone sialoprotein (BSP), which is expressed almost exclusively by osteoblasts at sites of de novo bone formation, OPN transcripts were present in cells lining both endosteal and periosteal bone surfaces, and in osteocytes. Moreover, expression of OPN persisted during the subsequent growth and remodelling of both membranous and endochondral bone and was expressed at particularly high levels by bone cells and hypertrophic chondrocytes at sites of osteoclastic resorption. In the more mature bone of young adult rats OPN expression was significantly reduced but remained detectable in bone cells lining periosteal and endosteal surfaces and in the primary and secondary spongiosa of the tibia. These studies on the developmental expression of OPN support the concept of a multifunctional role for OPN in bone formation and remodelling. Thus, the expression of OPN by osteoblasts early in bone development is consistent with a role for this protein in the formation of bone matrix, whereas the peak expression of OPN later in bone development, together with high expression at sites of rapid remodelling, indicate that OPN deposited on the surface of mineralized connective tissues may provide a template for osteoclastic resorption. PMID- 8492742 TI - A cartilage explant system for studies on aggrecan structure, biosynthesis and catabolism in discrete zones of the mammalian growth plate. AB - The structure, biosynthesis and catabolism of aggrecan has been studied in the bovine fetal rib growth plate. Comparative analyses were made on six 1-mm transverse slices which represent the resting zone (slice 6), proliferative zone (slices 5 and 4), upper hypertrophic zone (slice 3), middle hypertrophic zone (slice 2) and lower hypertrophic zone (slice 1). Aggrecan was abundant and exhibited very high aggregability in all zones. The aggrecan monomer was similar in structure in the resting and proliferative zones but showed a marked increase in hydrodynamic size in the lower hypertrophic zone; this was apparently due to an increase in the size of substituent glycosaminoglycans and an increase in core protein size as indicated by peptide analysis for G3 domain abundance. Biosynthetic studies with [35S]-sulfate showed the rate of synthesis per cell to be highest in the upper hypertrophic zone, and the structure of the newly synthesised molecules to be similar to the resident population in all zones. During explant culture in basal medium both aggregating and non-aggregating forms of aggrecan were released slowly from all zones. Addition of 10 nM retinoic acid to explants stimulated the release of both these forms of aggrecan whereas higher concentrations of retinoic acid (100 nM and 1000 nM) preferentially stimulated the release of the degraded forms. In this regard hypertrophic cells were the most responsive and resting cells were the least responsive. Analysis of the degraded fragments by polyacrylamide gel electrophoresis and by N-terminal sequencing indicated that aggrecan catabolism in all zones of the growth plate is due to the action of aggrecanase, a novel cartilage proteinase which is also active in normal and osteoarthritic articular cartilages (Sandy et al., 1992). These observations are discussed in terms of the role of aggrecan in the extensive matrix remodelling which accompanies chondrocyte hypertrophy in the growth plate. PMID- 8492743 TI - Characterization of the mouse type X collagen gene. AB - Type X collagen, a homotrimer of alpha 1 (X) polypeptide chains, is specifically expressed by hypertrophic chondrocytes in regions of cartilage undergoing endochondral ossification. We have previously characterized a genomic clone containing the major part of the mouse type X collagen gene (col10a1) and assigned the locus for col10a1 to mouse chromosome 10 (Apte et al., Eur. J. Biochem. 224: 217-224, 1992). In this paper, through additional characterization of cDNA and genomic clones, we describe the complete organization of the col10a1 gene. The col10a1 gene is 7.2 kb in size and, as in the chick, col10a1 gene transcripts are generated from only three exons. Exon 1 encodes only the 5' untranslated (5' UT) region of the mRNA and is separated from exon 2 by an intron 562 bp in length. Exon 2 (169 bp) encodes 15 bp of 5' UT message, the translation start plus 17-amino acid residues of the putative signal peptide, and 33 1/3 codons of the putative N-terminal non-collagenous (NC2) domain of type X collagen. Exon 3 is 2854 bp in size and encodes 4 2/3 codons of the NC2 domain, the entire collagenous domain of 463 residues (COL), the entire C-terminal non collagenous (NC1) domain (161 amino acid residues) and the entire 965 bp 3' untranslated (3' UT) sequence of the mRNA. Two TATA boxes are present in tandem in the col10a1 promotor. Both TATA boxes are active in transcription, generating two populations of transcripts with different 5'-termini; the longer transcript is of low abundance and is detectable only by PCR in newborn mice. The col10a1 promotor contains a CCAAT box as well as other consensus sequence elements required for binding of potential transcription factors. Characterization of the col10a1 gene provides data essential for studies of the regulation of type X collagen expression during mammalian endochondral bone growth and development. Knowledge of the complete structure of the mouse type X collagen gene will also be useful for the investigation of type X collagen gene abnormalities in murine chondrodysplasias and for the generation of transgenic mice. PMID- 8492744 TI - Direct evidence for active metalloproteinases mediating matrix degradation in interleukin 1-stimulated human articular cartilage. AB - When adult human articular cartilage was maintained in organ culture in the presence of interleukin 1 beta, increased destruction of the extracellular matrix was observed, as judged by increased type II collagen degradation in situ determined immunohistochemically and the increased release of proteoglycan into the culture medium. Concomitant with these changes was the increased release of latent metalloproteinases into the culture medium. Culture of cartilage in the presence of a peptidylhydroxamate metalloproteinase inhibitor indicated a key role for the active forms of these enzymes in situ, since it produced a marked reduction in both proteoglycan release and collagen degradation. This compound had no detectable cytotoxic effects in organ culture and did not reduce the secretion of the metalloproteinases. The results of this study provide direct evidence that the latent metalloproteinase precursors, whose release is greatly stimulated by interleukin 1, are indeed activated to some degree and participate in cartilage matrix degradation. PMID- 8492745 TI - Neuropeptide Y in neuroblastoma: increased concentration in metastasis, release during surgery, and characterization of plasma and tumor extracts. AB - Five children with neural crest tumors (two ganglioneuromas, one ganglioneuroblastoma, and two neuroblastomas) were investigated regarding neuropeptide Y-like immunoreactivity (NPY-LI) in tumor tissue and plasma at diagnosis and during surgery. Radioimmunoassay of extracted plasma revealed higher NPY-LI at diagnosis of neuroblastoma (640 and 230 pmol/L resp) than ganglioneuroblastoma or ganglioneuroma (74, 45, and 26 pmol/L resp). During surgery of neuroblastoma plasma NPY-LI increased two- to four-fold while no peroperative increase was seen in the other children. NPY-LI was considerably higher in neuroblastoma tissue (220 pmol/g and 144 pmol/g) than in ganglioneuroblastoma (40.2 pmol/g), ganglioneuroma (0.6 and 4.4 pmol/g), or healthy adrenal tissue (5.5 pmol/g). The highest NPY-LI concentration was found in neuroblastoma metastasis, 3,091 pmol/g. Gel-permeation chromatography of a neuroblastoma tumor showed that a majority of NPY-LI was representing intact NPY (NPY 1-36) while metastasis and plasma from the same child mainly contained smaller immunoreactive fragments. High concentrations of systemic NPY in neuroblastoma patients are of tumoral origin. Plasma levels of NPY and its fragments can be useful in diagnosing and monitoring neuroblastoma, and for early detection of relapse or metastatic disease. A possible involvement of NPY in neuroblastoma tumor growth and spread deserves further investigation. PMID- 8492746 TI - Diagnostic imaging in the surveillance of treated children with cancer. PMID- 8492747 TI - Ovarian function following the treatment of childhood acute lymphoblastic leukaemia. AB - Ovarian function was assessed in 40 long term survivors who had received standard United Kingdom Acute Lymphoblastic leukaemia (UKALL) protocols and were in first clinical and haematological remission. A menstrual and pregnancy history was taken (median age at assessment: 18.8 (12-34.7) years) and the acquisition of adult secondary sexual characteristics confirmed in each patient. Basal bloods were taken for follicle stimulating hormone (FSH), luteinizing hormone (LH), and serum oestradiol estimations. Serum progesterone concentration was measured in those patients who were in the luteal phase of their menstrual cycle at assessment. In addition, menstrual cycle profiles of salivary progesterone concentrations were derived from daily samples in 12 patients. All patients achieved adult sexual development; median age at menarche was early at 12.4 (9.0 14.6) years and 37 of them have regular menses. Ten patients have had 14 live births, and evidence of ovulation was seen in a further 11 patients assessed in the luteal phase of the menstrual cycle. Four patients had damaged ovaries, two of whom show evidence of ovulation; three of the four received craniospinal irradiation and one received cyclophosphamide as part of her chemotherapy regimen. None of these patients has yet developed total ovarian failure or required sex steroid replacement therapy. The medium term outlook for ovarian function is good for the majority of childhood ALL survivors. The spinal component of craniospinal irradiation is a major risk factor for ovarian damage, and cyclophosphamide may be a contributory factor. A premature menopause remains a possibility if significant follicular depletion has occurred at the time of cytotoxic treatment. PMID- 8492748 TI - Prognostic significance of myeloid-associated antigen expression on blast cells in children with acute lymphoblastic leukemia. The Austrian Pediatric Oncology Group. AB - The prognostic significance of expression of myeloid-associated antigens in childhood acute lymphoblastic leukemia (myA+ALL) was evaluated. From 1984 to 1990, 251 children with immunologically verified ALL were treated in two prospective consecutive Austrian studies. Complete immunophenotyping was performed in 206 cases (82%). Out of these 175 cases were classified as B-cell precursor ALL, 31 cases as T-ALL. Expression of myeloid-associated antigens was demonstrated in 23 cases (13.1%) of childhood B-cell precursor ALL, particularly in immature (CD10 negative) forms (P < .0001), and in 1 case (3.2%) of T-ALL. CDw65 was expressed most frequently (12 cases), followed by CD13 and CD15 (5 cases each), CD33 (4 cases), and blood-group H (3 cases). Compared to myA- ALL prognosis of children with myA+ B-cell precursor ALL was poor, despite intensive multiagent chemotherapy according to BFM protocols. Remission rates were not impaired, but pEFS was 74.6% for myA- ALL, and only 37.8% for myA+ ALL (P = .0001). As demonstrated by multivariate analysis the expression of myeloid associated antigens was the most important prognostic variable for EFS in B-cell precursor ALL, whether or not CD10 was expressed. PMID- 8492749 TI - T-Lymphocytes bearing the gamma delta T-cell receptor in cutaneous lesions of Langerhans' cell histiocytosis. AB - The aim of this study was to investigate the regional importance of gamma delta T cells in cutaneous lesions of Langerhans' cell histiocytosis. Six cases of Langerhans' cell histiocytosis were investigated by immunohistochemical techniques (alkaline phosphatase-antialkaline phosphatase complex and indirect immunoperoxidase). Increase of gamma delta T cells was observed in 3 cases of Langerhans' cell histiocytosis. In these cases up to 30% of CD3+ cells stained with an anti-TCR gamma delta monoclonal antibodies and in two of them gamma delta T cells showed a marked epidermotropism. In the specimens of the remaining three cases gamma delta T cells were found in an overall percentage of 5% of CD3+ cells, but in two cases a significant increase of epidermal gamma delta T cells was observed. The finding of numerous gamma delta T cells in Langerhans' cell histiocytosis is provocative and supports the suggestion of a functional relationship between gamma delta T cells and LCH cells. PMID- 8492750 TI - False-positive MRI detection of recurrent or metastatic pediatric infratentorial tumors. AB - Gadolinium-DTPA enhanced MRI is the modality of choice when imaging central nervous system infratentorial tumors in the pediatric population. The detection of a new enhancing lesion following initiation of therapy is typically considered pathognomonic for recurrent or metastatic tumor. We report two pediatric patients with infratentorial central nervous system tumors who demonstrated new areas of enhancement with gadolinium-DTPA enhanced MRI following initiation of multimodality therapy. Both patients had surgical biopsy of the new lesions with histologic review failing to demonstrate viable tumor. These studies suggest caution in considering new enhancing lesions detected by MRI in a child with a brain tumor pathognomonic for new sites of active tumor. PMID- 8492751 TI - Fever and granulocytopenia in children with cancer: a study of 299 episodes with two treatment protocols in Brazil. AB - In Brazil, 226 children with cancer presenting 299 episodes of fever and neutropenia (< or = 500/mm3) were treated with two consecutive empirical regimens. Regimen I-Cefoxitin Amikacin-Carbenicillin; and Regimen II Ceftriaxone Amikacin. 67.0% of the patients had leukemias or lymphomas, documented infections occurred in 47.2%, superinfections occurred in 18.7% (Reg. I) and 17.8% (Reg. II) of the episodes. The most common agents identified in Reg. I and Reg. II were, respectively, Gram negative rods (55.0%) and Gram positive cocci (52.6%). The overall rate of success with modifications (Amphotericin B, Vancomycin, Clindamycin, Metronidazole) was higher in Reg. II (93.0%) than in Reg. I (84.0%). This study shows that the appropriate formula to maximize the successful treatment of children with cancer, fever and neutropenia in developing nations includes adherence to established principles of supportive care, utilizing the optimal antibiotic agents available in the country. It is important to promote the necessary modifications along the treatment having in mind the high index of resistant agents. PMID- 8492752 TI - Gonadal stromal tumor of the testis in an infant. PMID- 8492753 TI - Resection of a solid and papillary epithelial neoplasm of the pancreas following treatment with cis-platinum and 5-fluorouracil: a case report. AB - A 15-year-old female was found at laparotomy to have an unresectable 15 cm solid and papillary epithelial neoplasm of the pancreas invading the superior mesenteric vein. The tumor regressed when treated with cis-platinum and 5 fluorouracil for 6 months leaving a 3.5 cm mass which was resected at reoperation. Response to chemotherapy has not been previously documented for this tumor histology and may contribute to the management of this locally invasive tumor. PMID- 8492754 TI - Isolated primary cutaneous aspergillosis of the labia. AB - Isolated cutaneous aspergillosis is a rare complication of severe immunocompromised states. We describe a case of isolated cutaneous aspergillosis of the labia minora in an adolescent undergoing treatment for relapsed acute non lymphocytic leukemia. The patient was successfully treated with a regimen that consisted of amphotericin B, granulocyte-colony stimulating factor, and surgical debridement. PMID- 8492755 TI - Re: "Etoposide in the treatment of six children with Langerhans cell histiocytosis (histiocytosis X)" by Viana et al. PMID- 8492756 TI - Transient respiratory depression in two patients with Down's syndrome following Midazolam premedication. PMID- 8492757 TI - Introduction: radiolabeled antibody tumor dosimetry. PMID- 8492758 TI - Selection of radionuclides for radioimmunotherapy. PMID- 8492759 TI - MIRD formulation. AB - The MIRD scheme is not restricted to calculating mean absorbed doses in organs but can be extended to any tissue for which distribution and retention data can be obtained and for which a reasonably accurate mathematical description of the source and target tissues can be determined. The development of more accurate absorbed dose estimates and the correlation of these estimates with radiation effects will lead to a better understanding of the results from radiotherapeutic agents such as radiolabeled monoclonal antibodies. Therefore, radiobiologists and internal dosimetrists need to combine their efforts and work toward the common goal of improving the treatment of malignant diseases. PMID- 8492760 TI - Pharmacokinetic modeling. AB - For radiation dosimetry calculations of radiolabeled monoclonal antibodies, (MAB), pharmacokinetics are critical. Specifically, pharmacokinetic modeling is a useful component of estimation of cumulated activity in various source organs in the body. It is thus important to formulate general methods of pharmacokinetic modeling and of pharmacokinetic data reduction, leading to cumulated activities. In this paper different types of models are characterized as "empirical," "analytical," and "compartmental" pharmacokinetic models. There remains a pressing need for quantitative studies in man for a proper understanding of the pharmacokinetics of MAb. Pharmacokinetic modeling of radiolabeled MAb in vivo has relied on relatively limited studies in man and complementary detailed measurements in animals. In either case, any model chosen for analysis of such data is inevitably based on measurements of limited accuracy and precision as well as assumptions regarding human physiology. Very few macroscopic compartmental pharmacokinetic models for MAb, have been tested over a range of conditions to determine their predictive ability. Extracorporeal immunoadsorption represents one approach for drastically altering the biokinetics of antibody distribution, and may serve to validate a given pharmacokinetic model. In addition to macroscopic modeling, the microscopic evaluation of the time dependent distribution of radiolabeled MAb in tissues is of utmost importance for a proper understanding of the kinetics and radiobiologic effect. Many tumors do not exhibit homogeneous uptake. A mathematical understanding of that distribution is thus essential for accurate tumor dosimetry estimates. This review summarizes methodologies for pharmacokinetic modeling, critically reviews specific pharmacokinetic models and demonstrates the capability of modeling for predictive calculations of altered pharmacokinetics, emphasizing its use in dosimetric calculations. PMID- 8492761 TI - Tumor dosimetry in radioimmunotherapy: methods of calculation for beta particles. AB - Calculational methods of beta-particle dosimetry in radioimmunotherapy (RIT) are reviewed for clinical and experimental studies and computer modeling of tumors. In clinical studies, absorbed-dose estimates are usually based on the in-vivo quantitation of the activity in tumors from gamma camera images. Because of the limited spatial resolution of gamma cameras, clinical dosimetry is necessarily limited to the macroscopic level (macrodosimetry) and the MIRD formalism for absorbed-dose calculations is appropriate. In experimental RIT, tumor dimensions are often comparable to or smaller than the beta-particle range of commonly used radionuclides (for example, 131I, 67Cu, 186Re, 188Re, 90Y) and deviations from the equilibrium dose must be taken into account in absorbed-dose calculations. Additionally, if small tumors are growing rapidly at the time of RIT, the effects of tumor growth will need to be included in absorbed-dose estimates. In computer modeling of absorbed-dose distributions, analytical, numerical, and Monte Carlo methods have been used to investigate the consequences of uniform and nonuniform activity distributions and the effects of inhomogeneous media. Measurements and calculations of the local absorbed dose at the multicellular level have shown that variations in this dose are large. Knowledge of the absorbed dose is essential for any form of radiotherapy. Therefore, it is important that clinical, experimental, and theoretical investigations continue to provide information on tumor dosimetry that is necessary for a better understanding of the radiobiological effects of RIT. PMID- 8492762 TI - Microdosimetric concepts in radioimmunotherapy. AB - In microdosimetry particular emphasis is placed on the stochastic fluctuation of dose in small target volumes such as individual cell nuclei or chromatin fiber, and their relevance to radiobiologic toxicity. Thus microdosimetry is intimately associated with models of radiation action. There are three principal areas where microdosimetry has been applied: (1) radiation protection, (2) high LET radiotherapy, e.g., neutron therapy, and (3) incorporated radionuclides, and in this latter category the importance of microdosimetry to the radiobiology of radiolabeled antibodies is becoming increasingly recognized. The objective of microdosimetry is the complete characterization of energy deposition within all target volumes throughout the tissue of interest. The importance and relevance of this pursuit will depend upon the properties of the radionuclide emissions and the spatial distribution of the radionuclide relative to the target volumes. If the distribution of internal emitters within both malignant and normal tissue is uniform, the application of microdosimetry to radioimmunotherapy (RIT) is limited to alpha-emitters and Auger emitters. Under such circumstances the traditional MIRD formalism for the evaluation of tumor and tissue doses from the commonly used beta-emitters is entirely adequate. This, however, is rarely the case. When the distribution of radiolabeled antibody is nonuniform, techniques of dose averaging over volumes greater in size than the individual target volumes can become inadequate predictors of the biological effect. The concepts, methods, and realm of applicability of microdosimetry within the field of radioimmunotherapy are emphasized in this paper. PMID- 8492763 TI - Multicellular dosimetry for beta-emitting radionuclides: autoradiography, thermoluminescent dosimetry and three-dimensional dose calculations. AB - Inhomogeneities in activity distributions over distances from 10 to 10(4) microns are observed in many tumors treated with radiolabeled antibodies. Resulting nonuniformities in absorbed dose may have consequences for the efficacy of radioimmunotherapy. Activity variations may be directly studied with quantitative autoradiography (ARG). Converting these data to absorbed dose distributions requires additional information about pharmacokinetics, the use of a point source function and consideration of the complete three-dimensional activity distribution, as obtained from sequential autoradiographic slices. Thermoluminescent dosimetry with specially prepared CaSO4:Dy dosimeters implanted into tissue can directly measure absorbed dose in selected regions. The conditions under which thermoluminescent dosimeters (TLD) are used differ markedly from "normal" use conditions in external beam radiotherapy. Therefore special calibration and quality assurance precautions are needed to assure the precision of this technique. Procedures and pitfalls in the use of both techniques in radioimmunotherapy are described. PMID- 8492764 TI - Experimental radioimmunotherapy. AB - Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492765 TI - An overview of imaging techniques and physical aspects of treatment planning in radioimmunotherapy. AB - Planar and tomographic imaging techniques and methods of treatment planning in clinical radioimmunotherapy are reviewed. In clinical trials, the data needed for dosimetry and treatment planning are, in most cases, obtained from noninvasive imaging procedures. The required data include tumor and normal organ volumes, the activity of radiolabeled antibodies taken up in these volumes, and the pharmacokinetics of the administered activity of radiolabeled antibodies. Therefore, the topics addressed in this review include: (1) Volume determination of tumors and normal organs from x-ray-computed tomography and magnetic resonance imaging, (2) quantitation of the activity of radiolabeled antibodies in tumors and normal organs from planar gamma camera views, (3) quantitative single-photon emission computed tomography and positron emission tomography, (4) correlative image analysis, and (5) treatment planning in clinical radioimmunotherapy. PMID- 8492766 TI - Radioimmunotherapy dose estimation in patients with B-cell lymphoma. AB - Trials of radiolabeled antibody therapy in patients with B-cell lymphoma have been the most promising of any in radioimmunotherapy. Response rates of greater than 90% with many complete remissions have been reported by several groups using either low (185-370 MBq) or high (8.6-22.5 GBq) doses of I-131-labeled antibodies against B-cell antigens. Estimated doses delivered to normal organs have ranged from 0.2 to 2.2 mGy/MBq and have shown similar interpatient variation in all series, despite differences in antibody specificity and dosimetric techniques. Tumor doses have ranged from 0.5 to 5.4 mGy/MBq. There has been little correlation of tumor response with estimated tumor dose. Toxicity has been limited to bone marrow suppression which has been greater with the higher amounts of I-131. An advantage for a particular antibody specificity or for high dose compared to multiple low doses has yet to be demonstrated. PMID- 8492767 TI - Dosimetry of solid tumors. AB - Dosimetry data arising from a decade of radioimmunotherapy are summarized along with techniques utilized to arrive at the reported dose estimates. Generality of the MIRD methodology allows it to serve as a vehicle for the calculation of solid tumor dosimetry although several limitations exist. Nonstandard geometries of solid tumors will ultimately necessitate determination of absorbed fractions for the individual tumors. Several approaches currently under investigation are described. For reasons of practicality, solid tumor dosimetry estimates continue to use the assumption of homogeneous activity distribution in a source organ, accounting for either all radiation or only nonpenetrating radiation. As computation tools become available for incorporating inhomogeneous cellular level data, the currently used "average dose" as an index of tumor sterilization will likely be replaced with a statistical distribution based on the number of viable cells in the tumor volume. Estimates of a tumor control dose would be based upon a linear extension of dose coupled with a threshold dose for cell sterilization. PMID- 8492768 TI - Dosimetry of intraperitoneally administered radiolabeled antibodies. AB - Intraperitoneal and intracavitary radioimmunotherapy differ from other approaches of radioimmunotherapy in that high activity and dose gradients exist near the solution/tumor interface. Dose to tumor and normal tissue at the interface is a function of depth and is due to three major components: (1) the activity concentration of the administered radiolabeled antibody solution as a function of time within the compartment; (2) the spatial distribution of antibody/radionuclide complex as a function of depth and time as the biomolecules bind to and permeate tumor/normal tissues; and (3) the physical characteristics of the radionuclide in relation to depth of antibody penetration. In this review, the biological and physical aspects of intraperitoneally administered radiolabeled antibodies are discussed, and the state of experimental and calculational studies for this site is described. Areas requiring future investigation are examined, and recommendations are made regarding the type of measurements and calculations which are required for accurate dosimetry. PMID- 8492770 TI - [99th Meeting of the German Society of Internal Medicine, Wiesbaden, 18 to 21 April 1993]. PMID- 8492769 TI - Radiobiology of radiolabeled antibody therapy as applied to tumor dosimetry. AB - This paper reviews the radiobiological aspects of radioimmunotherapy (RIT) with radiolabeled antibodies, including comparisons between RIT and external beam irradiation. The effectiveness of cell killing by radiation decreases with the dose rate and the rate of decrease is determined by the size of the shoulder on the radiation survival curve. Tumors with poor repair capabilities exhibit less of a dose rate effect than tumors with good repair capabilities. Continued tumor cell proliferation during treatment occurs at very low dose rates and can contribute to the reduced effectiveness of low dose rate radiation. Toxicity to normal tissues will determine the total dose of radiolabeled antibody that can be given and this will be influenced by the choice of both the radionuclide and the antibody. The reported enhanced effectiveness of RIT may be due to multiple factors including selective targeting of cells responsible for tumor volume doubling, tumor surface binding rather than homogeneous binding throughout the tumor volume, targeting of the tumor vasculature, or block of cell cycle progression in G2. During RIT, there is less time for reoxygenation of hypoxic tumor cells than during a course of conventional external beam radiotherapy. It has not yet been determined whether this will have a detrimental effect on RIT. Probably the most important factor in the success of RIT is dose heterogeneity. Any viable portion of a tumor that is not targeted and does not receive a significant radiation dose will potentially lead to treatment failure, no matter how high the dose received by the remainder of the tumor. Comparisons between RIT and external beam radiation have shown a wide range of relative efficacy. Tumors most likely to respond to RIT are tumors with poor repair capabilities, tumors that are susceptible to blockage in radiosensitive phases of the cell cycle, tumors that reoxygenate rapidly, and tumors that express the relevant antigen homogeneously. From a radiobiological perspective, it appears that RIT alone is unlikely to cure many tumors and that combination with other treatment modalities will be essential. PMID- 8492771 TI - [Loss of fibronectin receptor expression in malignant transformation of the colon results in increased tumorigenicity of epithelial cells]. AB - Following malignant transformation, epithelial cells of colorectal carcinomas unlike normal colonic epithelial cells do not any longer express the classical alpha 5 beta 1 fibronectin receptor. We speculated that the loss of alpha 5 beta 1 expression may facilitate the tumorigenicity of transformed colonic cells. To examine this hypothesis, we established subclones of the human colon adenocarcinoma cell line HT29 which differ in their fibronectin receptor expression and tested their tumorigenicity in nude mice. Our data indicate that the capacity to form tumors in nude mice after subcutaneous injection was significantly lower for alpha 5 beta 1-positive than for alpha 5 beta 1-negative cell clones. In addition, tumors from clones expressing to detectable levels of alpha 5 beta 1 grew rapidly, while tumors expressing elevated levels of fibronectin receptor grew slowly. Deposition of fibronectin in tumor-surrounding stroma was increased in tumors derived from alpha 5 beta 1-positive cells compared to tumors derived from alpha 5 beta 1-negative cells. Our results indicate that a reduction of the alpha 5 beta 1-mediated interaction of epithelial cells with the extracellular matrix may be responsible for increased tumorigenicity of malignant transformed cells in colorectal carcinomas. PMID- 8492772 TI - [Detection, localization and modulation of hyaluronic acid/CD44 receptor expression in patients with endocrine orbitopathy]. AB - Accumulation of hyaluronic acid within the orbital tissues represents a histological hallmark of Graves' ophthalmopathy. The hyaluronic acid/CD44 receptor plays a key role in the binding and metabolism of hyaluronic acid, and affects numerous cellular functions of potential relevance to the pathogenesis of Graves' ophthalmopathy, including cell proliferation, migration, and adhesive interactions between connective tissue components and immunocompetent cells. Using a highly sensitive immunoperoxidase technique and monoclonal antibodies directed against the standard CD44 molecule, we examined the expression and modulation of hyaluronic acid/CD44 receptors in cryostat sections of orbital biopsy specimens derived from patients with severe Graves' ophthalmopathy and normal individuals. Modulation of CD44 by cytokines and affinity-purified IgGs derived from patients with Graves' ophthalmopathy was studied in extracts of fibroblast monolayers following stimulation in vitro, using SDS-polyacrylamid gel electrophoresis and immunoblotting. Strong immunoreactivity for CD44 was present in all specimens derived from patients with Graves' ophthalmopathy and was detected in fibroblasts residing in retroorbital connective tissue, in extracellular matrix components and in mononuclear cell infiltrates. By contrast, in normal orbital specimens, CD44 immunoreactivity was faint and present only in occasional connective tissue cells. Recombinant IL-1 alpha, TNF alpha, IGF-1 and GO-IgGs significantly stimulated CD44 expression in Graves' retroocular fibroblasts (range: 168 to 588%; all p < 0.05). By contrast, EGF, IL-6, control IgGs and 15% fetal calf serum failed to alter CD44 expression. Treatment of monolayers with IFN gamma resulted in weak inhibition of CD44 expression. In conclusion, the hyaluronic acid/CD44 receptor is expressed at elevated levels in Graves' orbital connective tissue in situ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492773 TI - [Indications for different collagen metabolism in Crohn disease and ulcerative colitis]. AB - Very little is currently known regarding the underlying mechanisms involved in the etiology of intestinal strictures in chronic inflammatory bowel disease. The deposition of extracellular matrix components, especially collagens, is thought to play an important role in the etiology of intestinal strictures. The main goal of this study was therefore to investigate the collagen metabolism in patients with inflammatory bowel disease using the in situ hybridization technique. We determined de novo synthesis of the (pro)-collagen mRNA transcripts alpha 1I, alpha 1III, alpha 1IV, alpha 2V as well as the collagen degrading enzyme mRNA transcripts collagenase type I and IV in Crohn's disease and ulcerative colitis and compared the rate of expression semiquantitatively to healthy controls. We found a significant increase of all (pro)-collagen transcripts tested in Crohn's disease and ulcerative colitis as compared to healthy control tissues, indicating an increased de novo synthesis of all collagens in both inflammatory bowel diseases. However, we observed a significant difference in the expression of the collagenase mRNA transcripts between Crohn's disease and ulcerative colitis. Compared to healthy control subjects we were unable to detect a significant difference in the expression of collagenase type I and IV in Crohn's disease; in contrast, we observed a significant increase in the rate of expression for the collagenases in ulcerative colitis as compared to controls or biopsies from patients with Crohn's disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492774 TI - [N-acetylcysteine decreases functional and structural, ARDS-typical lung changes in endotoxin-treated rats]. AB - Oxygen radicals and oxygen radical mediators derived from activated granulocytes are important components in the development of acute lung injury, namely the adult respiratory distress syndrome ARDS. N-acetylcysteine (NAC) is one important substance for endogenous production of reduced glutathion, which is known to be an intra- and extracellular reducing agent also found in lung tissue. We evaluated the effect of exogenous NAC on the endotoxin induced development and course of ARDS in rats. ARDS-like injury was induced in rats via intraperitoneal injection of Salmonella enteritidis endotoxin 30 mg/kg body weight. NAC or solvent was injected intraperitoneally 30 min prior to, at the time of and 30 min after injection of endotoxin respectively with 150 mg/kg body weight each dose. Endotoxin injection in rats resulted in 80% mortality within 72 hours, increased lung wet weight, severe ultrastructural lung damage as measured by histological methods. In isolated, ventilated, with physiological salt solution perfused rat lungs vasocontractility was severely blunted, lung albumin leakage was increased, thromboxane B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) perfusate levels were increased. NAC treatment significantly improved survival of endotoxin treated rats, ameliorated structural lung damage, diminished lung wet weight and lung albumin leakage, lowered lung perfusate TXB2 and 6-keto-PGF1 alpha levels and slightly improved vasocontractility in isolated perfused lungs. Therefore, NAC significantly ameliorates ARDS-like lung injury in rats, when given in vivo. PMID- 8492775 TI - [Autoregulation of kidney circulation, glomerular filtration rate and plasma renin activity in spontaneously hypertensive rats and normotensive Wistar rats]. AB - The autoregulation of renal blood flow (RBF), glomerular filtration rate (GFR) and the pressure dependent renin release into the circulation were studied in conscious chronically instrumented spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Renal perfusion pressure was lowered by means of a suprarenal inflatable cuff on the abdominal aorta and was lowered in pressure steps of 10 mm Hg. Breakoff points for RBF- and GFR-autoregulation as well as the threshold for renin release were calculated using non-linear regression (breakpoint analysis). Wistar rats autoregulated RBF and GFR in a range between 110 and 90 mm Hg (breakoff points: RBF 88 +/- 2 mm Hg; GFR 92 +/- 3 mm Hg). Plasma-renin activity (PRA) showed a threshold of activation at 89 +/- 8 mm Hg. Breakoff points and threshold of renin release did not differ significantly from each other. SHR autoregulated RBF and GFR in a range between 160 and 100 mm Hg (breakoff points: RBF 104 +/- 6 mm Hg; GFR 99 +/- 4 mm Hg). The PRA increase had a threshold at 119 +/- 6 mm Hg. Breakoff points of RBF- and GFR-autoregulation did not differ significantly. In SHR the threshold of renin release was at a significantly higher pressure than the breakoff point of GFR-autoregulation. The comparison between Wistar rats and SHR revealed a significant shift of the RBF autoregulation curve and the pressure-dependent renin release of SHR towards higher pressures (p < 0.05). The early increase of PRA in SHR suggests a role of the renin-angiotensin-system (RAS) in the autoregulation of GFR in SHR. Wistar rats seem to autoregulate GFR independently of the RAS. An activation of the sympathetic nervous system might take part in the rightward shift of the RBF- and GFR-autoregulation curve in SHR. The role of this altered autoregulatory pattern in the development of genetic hypertension remains to be investigated. PMID- 8492776 TI - [Molecular analysis of pulmonary risk genes. Relevance for clinical research, diagnosis and therapy]. PMID- 8492777 TI - [Prevention of acute lung failure (ARDS)]. PMID- 8492778 TI - [Prevention of nosocomial pneumonia]. PMID- 8492779 TI - [Prevention of acute renal failure]. PMID- 8492780 TI - [Prevention of gastrointestinal stress lesions]. PMID- 8492781 TI - [Prevention in intensive care medicine]. PMID- 8492782 TI - [Principles of medical decision making]. PMID- 8492783 TI - [Accidental transmission of type-1 diabetes mellitus with HLA-identical bone marrow]. PMID- 8492784 TI - Reappraisal of regional thiamine content in the central nervous system of the normal and thiamine-deficient mice. AB - The regional distribution of thiamine and its phosphate esters was measured in the central nervous system (CNS) of normal and thiamine-deficient mice. Twelve small areas were punched out from frozen sections and they were individually analyzed by high performance liquid chromatography (HPLC). Regional difference was noted in both the content and ratio of thiamine and its phosphate esters in the normal CNS. In pyrithiamine-induced thiamine deficiency, thiamine pyrophosphate (TPP) content in all the areas was reduced to less than 13% of the control values on day 10, when the neurological signs developed. Although there were considerable regional variations in the reduction rate of thiamine and its phosphate esters, no correlation was established between the severity of tissue damage and the magnitude of thiamine reduction in individual areas. These results indicate that a derangement in TPP-dependent processes, either alone or in combination with other factors, plays a more critical role in the neuronal damage under thiamine deficiency than depletion of thiamine compounds per se. PMID- 8492785 TI - Cerebral amino acid changes in an animal model of intrauterine growth retardation. AB - As part of a series of experiments to ascertain the effects of prenatal malnutrition on brain development, we measured brain amino acids in an animal model of intrauterine growth retardation (IUGR) obtained by restriction of blood supply to the fetus in utero during the last 5 days of gestation. In the present study, amino acids were measured during development by HPLC as their O phthaldialdehyde derivatives in cerebral cortex, cerebellum and hippocampus. In rats with IUGR, significant increase of alanine (by 20% to 50%) and taurine (by 20% to 80%) were observed prior to weaning in the cerebellum and the cerebral cortex respectively. Alanine levels were also increased in hippocampus. In control animals, at birth, activities of the GABA nerve terminal marker enzyme glutamic acid decarboxylase (GAD) were found to be 32%, 17%, and 11% of adult values in cerebellum, hippocampus and cerebral cortex respectively. Two-day-old rats with IUGR had significantly lower GAD activities in all brain regions. Thus, impairment of nutrient supply to fetal brain results in selective regional abnormalities of amino acids particularly in the cerebral cortex. PMID- 8492786 TI - The new demographics. PMID- 8492787 TI - Health system reform. PMID- 8492788 TI - Medicare has changed its reimbursement for multiple endoscopic procedures done in the same day. PMID- 8492789 TI - Electronic claims filing. PMID- 8492790 TI - Diabetes in Missouri: prevalence and high-risk populations. AB - Diabetes was reported as an underlying or contributory cause of 3,706 deaths among Missouri residents in 1991, and the estimated direct and indirect costs of the disease in the state exceeded $450 million. Behavioral Risk Factor Surveillance System data indicate that, although diabetes is prevalent throughout the state's population, it is more prevalent among females, elderly persons, minority races, and persons with low educational and income levels. Individual practitioners should emphasize the reduction of health risk factors among their diabetic patients. Through regular monitoring of risks for diabetic complications and early intervention, a significant number of diabetic complications can be prevented or delayed. PMID- 8492791 TI - Missouri's two "anti-hassle" committees discuss Medicare/Part-B carriers' policies. PMID- 8492792 TI - National health insurance. PMID- 8492793 TI - Standards for pediatric immunization practices. Recommended by the National Vaccine Advisory Committee. AB - Although 97%-98% of children in the United States are vaccinated before or shortly after starting school, the proportion of preschool children who have completed a full series for all recommended vaccines is considerably lower. Although low immunization coverage among preschoolers has been attributed to difficulties in reaching certain groups, such as the urban poor and racial and ethnic minorities, more recent evaluations suggest that the health-care delivery system itself bears much of the responsibility. To eliminate barriers and obstacles (e.g., appointment-only systems and unnecessary prevaccination physical examinations) that impede efficient vaccine delivery and to encourage providers to take advantage of all health-care visits as opportunities to provide vaccinations, the National Vaccine Advisory Committee (NVAC) called for the development of standards for immunization policies and practices. Eighteen standards were developed in collaboration with a 35-member working group representing 22 public and private agencies. These 18 standards have since been recommended by the NVAC, approved by the U.S. Public Health Service, and endorsed by the American Academy of Pediatrics. The standards are presented and discussed in detail in this report. PMID- 8492794 TI - Update: influenza activity--United States, 1992-93 season. AB - Influenza activity in the United States increased from December 1992 through mid February 1993; during this period, influenza type B viruses circulated at high levels nationwide. However, since late February, high levels of influenza type A have been reported. This report updates surveillance for influenza during the 1992-93 season. PMID- 8492795 TI - Lead poisoning in bridge demolition workers--Georgia, 1992. AB - Bridge demolition and maintenance are leading causes of lead poisoning among workers in the United States. In June 1992, a local health department in Georgia detected elevated blood lead levels (BLLs) in four demolition workers. This report summarizes the investigation of these cases. PMID- 8492796 TI - Sexual behavior and condom use--District of Columbia, January-February, 1992. AB - From 1980 through 1990, the cumulative incidence of acquired immunodeficiency syndrome (AIDS) in the District of Columbia (DC) (2713 cases per 100,000 persons) was approximately eight times that of the surrounding metropolitan area (340 per 100,000) (1). From 1980 through 1986, the AIDS epidemic primarily involved men who had sex with men; since 1986, the incidence of AIDS has been increasing among injecting-drug users (IDUs) and their sex partners (1). Although AIDS incidence in DC has been projected to increase by 34% from 1990 to 1994 (1), patterns of sexual behavior and condom use are unknown among homosexual/bisexual men, IDUs, and other heterosexuals in DC and other urban areas with a high incidence of AIDS. To obtain current data on human immunodeficiency virus (HIV)-related knowledge and behavior, the DC Commission of Public Health (CPH) conducted a telephone survey of DC residents regarding HIV-related knowledge, number of sex partners, and condom use during the 1-year period preceding the survey. This report summarizes results of the survey. PMID- 8492797 TI - Childbearing patterns among selected racial/ethnic minority groups--United States, 1990. AB - Childbearing patterns in the United States reflect marked increases in and variation among different racial/ethnic groups. Groups with high rates of teenage childbearing traditionally have elevated risks for low birthweight (LBW [< 2500 g (5 lb 8 oz)]) and other poor birth outcomes associated with serious infant morbidity, permanent disability, and death. To characterize childbearing variations among American Indians/Alaskan Natives, Asians/Pacific Islanders, and Hispanic ethnic groups, CDC's National Center for Health Statistics analyzed data from U.S. birth certificates for 1990. PMID- 8492798 TI - The sequence-specific nuclear matrix binding factor F6 is a chicken GATA-like protein. AB - The sequence-specific DNA-binding protein factor F6, which binds upstream of the cluster of the chicken alpha-globin genes, has previously been found to interact with a DNA fragment containing a replication origin and a nuclear matrix binding site. This protein has been partially characterized. Based on its molecular weight and binding affinity, F6 belongs to a family of GATA proteins, the chicken equivalent of transcription factor NFE-1. An oligonucleotide including the binding site for F6 competes for binding of the above-mentioned DNA fragment to the nuclear matrix. This indicates an involvement of this protein in the interaction between DNA and the nuclear matrix. PMID- 8492799 TI - Isolation of the DLD gene of Saccharomyces cerevisiae encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase. AB - In Saccharomyces cerevisiae the utilization of lactate occurs via specific oxidation of L- and D-lactate to pyruvate catalysed by L-lactate ferricytochrome c oxidoreductase (L-LCR) (EC 1.1.2.3) encoded by the CYB2 gene, and D-lactate ferricytochrome c oxidoreductase (D-LCR) (EC 1.1.2.4), respectively. We selected several lactate- pyruvate+ mutants in a cyb2 genetic background. Two of them were devoid of D-LCR activity (dld mutants, belonging to the same complementation group). The mutation mapped in the structural gene. This was demonstrated by a gene dosage effect and by the thermosensitivity of the enzyme activity of thermosensitive revertants. The DLD gene was cloned by complementation for growth on D-, L-lactate in the strain WWF18-3D, carrying both a CYB2 disruption and the dld mutation. The minimal complete complementing sequence was localized by subcloning experiments. From the sequence analysis an open reading frame (ORF) was identified that could encode a polypeptide of 576 amino-acids, corresponding to a calculated molecular weight of 64000 Da. The deduced protein sequence showed significant homology with the previously described microsomal flavoprotein L gulono-gamma-lactone oxidase isolated from Rattus norvegicus, which catalyses the terminal step of L-ascorbic acid biosynthesis. These results are discussed together with the role of L-LCR and D-LCR in lactate metabolism of S. cerevisiae. PMID- 8492800 TI - Transcript identification in the optomotor-blind locus of Drosophila melanogaster by intragenic recombination mapping and PCR-aided sequence analysis of lethal point mutations. AB - The optomotor-blind gene of Drosophila melanogaster is large and genetically complex. Five partly independent complementation groups are uncovered by several viable and lethal mutations at the locus. At least 15 RNA signals have been detected by Northern blot analysis. One of them, T3, derived from a 75 kb primary transcript, has been proposed as the carrier of optomotor-blind function, based on the large size of its precursor and its tissue distribution. We here provide direct evidence that T3 is the optomotor-blind transcript. A facile and generally applicable selection scheme for the isolation of intragenic meiotic recombinants was applied to map two lethal optomotor-blind point mutations to exons of the T3 transcript. Amplification of mutant DNA by the polymerase chain reaction (PCR) and sequencing of the amplified exons revealed the presence of mutations that lead to truncation of the T3 open reading frame. The recombination rate observed in the optomoter-blind locus is within the range of rates that have been determined in a few other Drosophila loci. PMID- 8492801 TI - pR plasmid replication provides evidence that single-stranded DNA induces the SOS system in vivo. AB - Evidence is presented that the pR bat gene is essential for plasmid replication and for spontaneous induction of the SOS response in Escherichia coli. Mutations preventing single-stranded DNA production, needed for pR plasmid replication, also prevent the induction of the SOS system. The following experimental design was used. Firstly, we identified the minima rep region, defined as the minimal DNA sequence necessary for pR plasmid replication and, secondly, analyzed the nucleotide sequence of this region. This identified structures and functions (ori plus, ori-minus and Rep protein) homologous to those found in phages and plasmids replicating by the rolling-circle mechanism. Finally, mutations were introduced either in the replication protein catalytic site or in the nick site consensus sequence, which caused the pR plasmid to lose its ability to induce the SOS system. We conclude that, in this system, the in vivo SOS-inducing signal appears to be the single-stranded DNA produced during pR replication. PMID- 8492802 TI - Origin of the main class of repetitive DNA within selected Pennisetum species. AB - In an attempt to identify relationships among genomes of the allotetraploid Pennisetum purpureum Schumach and closely related Pennisetum species with which it can be successfully hybridized, repetitive DNA sequences were examined. Digestion with KpnI revealed two highly repetitive fragments of 140 bp and 160 bp. The possibility that these sequences could be used as genome markers was investigated. Average sequences were determined for the 140 bp and 160 bp KpnI families from P. purpureum and P. squamulatum Fresen. Average sequences (based upon four or five repeats) were determined for the P. glaucum (L.) R. Br. 140 bp KpnI family and the diploid P. hohenackeri Hochst. ex Steud. 160 bp KpnI family. The average sequences of the 160 bp KpnI families in P. purpureum and P. squamulatum differ by only nine bases. The 140 bp KpnI families of the three related species, P. purpureum, P. squamulantum, and P. glaucum are nearly identical, and thus likely represent a recent divergence from a common progenitor or a common genome. Each repetitive sequence may contain internal duplications, which probably diverged following amplification of the original sequence. The 140 bp KpnI repeat probably evolved from the 160 bp KpnI repeat since the missing 18 bp segment is part of the internal duplication that is otherwise conserved in the subrepeats. Tandemly arrayed repetitive sequences in plants are likely to be composed of subrepeats which have been duplicated and amplified. PMID- 8492803 TI - Expression of the triose phosphate translocator gene from potato is light dependent and restricted to green tissues. AB - The export of primary photosynthesis products from chloroplasts into the cytoplasm is mediated by the triose phosphate translocator. The transporter is an integral membrane protein localized at the inner envelope of chloroplasts. In order to study the expression of the major chloroplast envelope protein gene E29, which is assumed to function as the translocator, we have isolated corresponding cDNA clones from potato. A full-length clone was sequenced and shown to be highly homologous to the E29 gene from spinach. Expression on the RNA level is restricted to green tissues, is light dependent and cannot be induced by sucrose in darkness. The presence of a single-copy gene argues for the existence of different translocator systems responsible for import and export of carbohydrates in chloroplasts and amyloplasts. PMID- 8492804 TI - Identification of a gene family (kat) encoding kinesin-like proteins in Arabidopsis thaliana and the characterization of secondary structure of KatA. AB - A gene family, designated kat, has been characterized in Arabidopsis thaliana by genomic Southern hybridization and nucleotide sequencing analysis. The kat gene family includes at least five members, named katA, katB, katC, katD and katE, whose products share appreciable sequence similarities in their presumptive ATP binding and microtubule-binding motifs with known kinesin-like proteins. The carboxyl-terminal region of the KatA protein deduced from the nucleotide sequence of the cDNA clone has considerable homology with the mechanochemical motor domain of the kinesin heavy chain. The predicted secondary structure of the KatA protein indicates two globular domains separated by a long alpha helical coiled coil with heptad repeat structures, such as are commonly found in kinesin-like proteins. PMID- 8492805 TI - Nucleotide sequence and genetic analysis of the Rhodobacter capsulatus ORF6-nifUI SVW gene region: possible role of NifW in homocitrate processing. AB - DNA sequence analysis of a 3494-bp HindIII-BclI fragment of the Rhodobacter capsulatus nif region A revealed genes that are homologous to ORF6, nifU, nifS, nifV and nifW from Azotobacter vinelandii and Klebsiella pneumoniae. R. capsulatus nifU, which is present in two copies, encodes a novel type of NifU protein. The deduced amino acid sequences of NifUI and NifUII share homology only with the C-terminal domain of NifU from A. vinelandii and K. pneumoniae. In contrast to nifA and nifB, which are almost perfectly duplicated, the predicted amino acid sequences of the two NifU proteins showed only 39% sequence identity. Expression of the ORF6-nifUISVW operon, which is preceded by a putative sigma 54 dependent promoter, required the function of NifA and the nif-specific rpoN gene product encoded by nifR4. Analysis of defined insertion and deletion mutants demonstrated that only nifS was absolutely essential for nitrogen fixation in R. capsulatus. Strains carrying mutations in nifV were capable of very slow diazotrophic growth, whereas ORF6, nifUI and nifW mutants as well as a nifUI/nifUII double mutant exhibited a Nif+ phenotype. Interestingly, R. capsulatus nifV mutants were able to reduce acetylene not only to ethylene but also to ethane under conditions preventing the expression of the alternative nitrogenase system. Homocitrate added to the growth medium repressed ethane formation and cured the NifV phenotype in R. capsulatus. Higher concentrations of homocitrate were necessary to complement the NifV phenotype of a polar nifV mutant (NifV-NifW-), indicating a possible role of NifW either in homocitrate transport or in the incorporation of this compound into the iron-molybdenum cofactor of nitrogenase. PMID- 8492806 TI - Adenine phosphoribosyltransferase genes in two Drosophila species: dosage compensation, a nuclear matrix attachment site, and a novel intron position. AB - The Aprt locus of Drosophila encodes the structural gene for the purine salvage enzyme adenine phosphoribosyltransferase. Aprt is autosomal and enzyme activity is gene-dose-dependent in Drosophila melanogaster. However, Aprt is X-linked and dosage compensated in Drosophila pseudoobscura, as shown here. The Aprt genes of both Drosophila species contain a DNA sequence associated with nuclear matrix attachment sites and these Aprt sequences specifically bind to nuclear matrix in vitro. Putative promoter sequences positioned upstream of the predicted transcriptional start site in the two Aprt genes have a similar structure of direct repeats with an overlapping dyad symmetry, but the DNA sequence of these motifs is not conserved between the two species. Biological features in mutants of Aprt as well as natural variants suggest that dosage compensation of this gene in Drosophila pseudoobscura is due to a general control mechanism on X-linked genes rather than a gene-specific mechanism. PMID- 8492807 TI - Expression of the Saccharomyces cerevisiae RAD50 gene during meiosis: steady state transcript levels rise and fall while steady-state protein levels remain constant. AB - In Saccharomyces cerevisiae, the RAD50 gene is required for repair of X-ray and MMS-induced DNA damage during vegetative growth, and for synaptonemal complex formation and genetic recombination during meiosis. We show below that the RAD50 gene encodes major and minor transcripts of 4.2 and 4.6 kb in length which differ primarily at their 5' ends. Steady-state levels of both RAD50 transcripts increase coordinately during meiosis, reaching maximal levels midway through meiotic prophase, about 3 or 4 h after transfer of cells to sporulation medium. The 5' ends of the major RAD50 transcript in both meiotic and vegetative cells map to the same cluster of sites approximately 20 bp upstream of the amino terminal ATG of the RAD50 coding sequence. We conclude that the increased RAD50 transcript level observed during meiosis does not reflect utilization of a new promoter. In contrast, steady-state levels of Rad50 protein do not increase during meiosis. Thus, changes in RAD50 transcript levels are not necessarily accompanied by commensurate changes in Rad50 protein levels. Possible explanations are considered. PMID- 8492808 TI - Abscisic acid-insensitive mutations provide evidence for stage-specific signal pathways regulating expression of an Arabidopsis late embryogenesis-abundant (lea) gene. AB - An Arabidopsis homolog of the abscisic acid (ABA)-inducible cotton D19 and wheat Em genes was cloned and its expression assayed at two developmental stages in wild-type, ABA-deficient (aba) and three ABA-insensitive (abi) lines of Arabidopsis thaliana. Expression of this gene was reduced slightly in seeds of aba mutants and approximately ten-fold in abi3 mutants, but seed expression was not decreased in either abi1 or abi2 monogenic mutants. In contrast, the abi1 and abi2 mutants showed a very slight reduction of ABA inducibility in 8-day-old plants, while the responses of aba and abi3 mutants were comparable to that of wild type. Although previous studies have shown that none of the abi mutations show completely stage-specific effects, the results reported here indicate that the importance of each of the ABI loci in regulating this single gene is stage dependent. Furthermore, the fact that none of the abi mutations show more than minor effects on exogenous ABA inducibility of the Arabidopsis D19/Em homolog in young plants suggests that an additional ABA signalling pathway may be operating during vegetative growth. PMID- 8492809 TI - Two different Em-like genes are expressed in Arabidopsis thaliana seeds during maturation. AB - Using a radish cDNA probe, we have isolated and characterized two genomic clones from Arabidopsis thaliana (GEA1 and GEA6) encoding two different proteins that are homologous to the "Early methionine-labelled" (Em) protein of wheat. GEA1 differs from GEA6 and Em clones of wheat in that a sequence coding for 20 amino acid residues is tandemly repeated 4 times. These two genomic clones correspond to two genes named AtEm1 and AtEm6. Sequencing of several cDNA clones showed that both genes are expressed. The transcription start site was determined for both genes by RNase mapping. The site of polyadenylation is variable and there is no obvious consensus sequence for polyadenylation at the 3' ends of the genes. mRNA corresponding to GEA6 is present only in nearly dry and dry seeds, whereas the corresponding to GEA1 appears in immature seeds and is maximum in dry seeds. No expression of either gene could be detected in leaf, stem, or floral buds. Expression of both genes could be detected in immature seeds when the siliques were incubated with abscisic acid (ABA), demonstrating that both genes are ABA responsive. However, examination of the 5' upstream region does not reveal any extensive homology, suggesting that regulation of the two genes differs. In situ hybridization with a GEA1 probe demonstrated that the expression of this gene is essentially located in the provascular tissues of the cotyledons and axis of the dry seed as well as in the epiderm and outer layers of the cortex in the embryo axis. PMID- 8492810 TI - Molecular diversity at the self-incompatibility locus is a salient feature in natural populations of wild tomato (Lycopersicon peruvianum). AB - A cDNA encoding a stylar protein was cloned from flowers of self-incompatible wild tomato (Lycopersicon peruvianum). The corresponding gene was mapped to the S locus, which is responsible for self-incompatibility. The nucleotide sequence was determined for this allele, and compared to other S-related sequences in the Solanaceae. The S allele was used to probe DNA from 92 plants comprising 10 natural populations of Lycopersicon peruvianum. Hybridization was conducted under moderate and permissive stringencies in order to detect homologous sequences. Few alleles were detected, even under permissive conditions, underscoring the great sequence diversity at this locus. Those alleles that were detected are highly homologous. Sequences could not be detected in self-incompatible Nicotiana alata, self-compatible L. esculentum (cultivated tomato) or self-compatible L. hirsutum. However, hybridization to an individual of self-incompatible L. hirsutum revealed a closely related sequence that maps to the S locus in this reproductively isolated species. This supports the finding that S locus polymorphism predates speciation. The extraordinarily high degree of sequence diversity present in the gametophytic self-incompatibility system is discussed in the context of other highly divergent systems representing several kingdoms. PMID- 8492811 TI - Modular organization and development activity of an Arabidopsis thaliana EF-1 alpha gene promoter. AB - The activity of the Arabidopsis thalana A1 EF-1 alpha gene promoter was analyzed in transgenic Arabidopsis plants. The 5' upstream sequence of the A1 gene and several promoter deletions were fused to the beta-glucuronidase (GUS) coding region. Promoter activity was monitored by quantitative and histochemical assays of GUS activity. The results show that the A1 promoter exhibits a modular organization. Sequences both upstream and downstream relative to the transcription initiation site are involved in quantitative and tissue-specific expression during vegetative growth. One upstream element may be involved in the activation of expression in meristematic tissues; the downstream region, corresponding to an intron within the 5' non-coding region (5'IVS), is important for expression in roots; both upstream and downstream sequences are required for expression in leaves, suggesting combinatorial properties of EF-1 alpha cis regulatory elements. This notion of specific combinatorial regulation is reinforced by the results of transient expression experiments in transfected Arabidopsis protoplasts. The deletion of the 5'IVS has much more effect on expression when the promoter activity is under the control of A1 EF-1 alpha upstream sequences than when these upstream sequences were replaced by the 35S enhancer. Similarly, a synthetic oligonucleotide corresponding to an A1 EF-1 alpha upstream cis-acting element (the TEF1 box), is able to restore partially the original activity when fused to a TEF1-less EF1-alpha promoter but has no significant effect when fused to an enhancer-less 35S promoter. PMID- 8492812 TI - Promoter analysis of the PHO81 gene encoding a 134 kDa protein bearing ankyrin repeats in the phosphatase regulon of Saccharomyces cerevisiae. AB - The PHO81 gene encoding one of the regulators of the phosphatase regulon in Saccharomyces cerevisiae was mapped 9.8 centimorgans distal from the ser2 locus on the right arm of chromosome VII. Determination of the nucleotide sequence of cloned PHO81 DNA revealed a 3537 bp open reading frame encoding a 134 kDa protein. This protein has six repeats of a 33-amino acid sequence homologous to the ankyrin repeat and an asparagine-rich region. Transcription of PHO81 is activated by Pho4 protein in cooperation with Pho2 (i.e., Bas2/Grf10) protein under the influence of the inorganic phosphate (Pi) concentration in the medium, through the PHO regulatory system. Major transcription initiation sites of PHO81, determined by primer extension analysis, are at nucleotide positions -66 and -65 relative to the ATG codon. Deletion analysis showed that a 95 bp region from nucleotide position -385 to -291 is essential for response to the Pi signals. Purified Pho4 protein protected a 19 bp region (positions -350 to -332) in the 95 bp fragment from DNase I digestion in vitro and the protected region includes the core sequence 5'-CACGTG-3', which is also observed in other genes of phosphate metabolism. PMID- 8492813 TI - Random mutagenesis of the gene for bacteriophage T7 RNA polymerase. AB - Random mutagenesis of the gene for bacteriophage T7 RNA polymerase was used to identify functionally essential amino acid residues of the enzyme. A two-plasmid system was developed that permits the straightforward isolation of T7 RNA polymerase mutants that had lost almost all catalytic activity. It was shown that substitutions of Thr and Ala for Pro at the position 563, Ser for Tyr571, Pro for Thr636, Asp for Tyr639 and of Cys for Phe646 resulted in inactivation of the enzyme. It is noteworthy that all these mutations are limited to two short regions that are highly conservative in sequences of monomeric RNA polymerases. PMID- 8492814 TI - Protecting patients from HIV infection: who's responsible? PMID- 8492815 TI - The "way it was". PMID- 8492816 TI - Defining care parameters. PMID- 8492817 TI - Presidential address. PMID- 8492818 TI - Conjoint report to the North Carolina Medical Society and the North Carolina Commission for Health Services. PMID- 8492819 TI - Let the people go. Caring for the demented elderly without using restraints. PMID- 8492820 TI - Skin cancer. PMID- 8492821 TI - Patient perceptions of medical urgency at the time of discharge from the emergency department. PMID- 8492822 TI - Irony upon irony. Internal medicine at the crossroads of the crisis in medicine and health care (and what we are trying to do about it at Bowman Gray). PMID- 8492823 TI - Becoming brother's keeper. Legal responsibilities of those supervising care by residents. PMID- 8492824 TI - The threat to the medical profession in its attempt to discipline itself. PMID- 8492825 TI - Branch retinal artery occlusion. A possible adverse effect of chelation therapy. PMID- 8492826 TI - Running the race. Two physicians reflect on their political experiences. PMID- 8492827 TI - Gallup Poll surveys views on organ donation. PMID- 8492828 TI - Who should place peritoneal catheters? A nephrologist's view. PMID- 8492829 TI - Minntech sues authors of new report on dialyzer reuse. PMID- 8492830 TI - [The hypotonic infant: how limp is too limp?]. PMID- 8492831 TI - [Magnetic resonance images and spectroscopy in multiple sclerosis]. PMID- 8492832 TI - [Cerebral magnetic resonance tomography in multiple sclerosis]. PMID- 8492833 TI - [Diagnosis of ischemic heart diseases using magnetic resonance techniques]. PMID- 8492834 TI - [3 examples of fetal genetic neuromuscular disorders which lead to hydramnion]. AB - Causes of polyhydramnios include foetal neuromuscular disorders which cause inability of the foetus to swallow amniotic fluid. Three examples of such disorders are presented: X-linked myotubular myopathy, congenital myotonic dystrophy, and congenital nemaline myopathy. It is concluded that in case of polyhydramnios a search for foetal neuromuscular disease should be carried out. This implies ultrasound evaluation of the foetal movements, especially swallowing movements, neurological examination of the mother for myotonic dystrophy and examination of the newborn, which in selected cases includes muscle biopsy. Foetal neuromuscular disorders are usually genetic in origin. This adds to the need for accurate diagnosis and proper genetic counseling. PMID- 8492835 TI - [Unintended urine loss in women during sexual activities; an exploratory study]. AB - Urinary incontinence can have a profound negative impact on female sexuality. Not only feelings of shame and loss of libido are important; complaints of urine loss during sexual activity can also exist. The prevalence of this phenomenon was examined in a study of 245 patients complaining of urinary incontinence. We also analysed the evoking moments and the impact of the complaint on the sexual relation. 20% of the patients had no partner. 66 (34%) of the remaining women reported losing urine during sexual activity. It was often experienced during pressure on the abdomen and deep vaginal penetration. Non-mechanical factors played an important part as well. Neither the history nor the urodynamic diagnosis had a clear relationship with evoking moments during intercourse. Incontinence was frequently (also) experienced during orgasm and sexual excitement. We found a strong negative effect of this complaint on the sexual lives of many women and their partners. Adequate relief of stress incontinence by colpo-suspension will also stop urine loss during intercourse. PMID- 8492836 TI - [Clinimetric evaluation of the Barthel Index, a measure of limitations in dailly activities]. AB - OBJECTIVE: Evaluation of the clinimetric properties of the Barthel Index. DESIGN: To measure disabilities in activities of daily living (ADL) and mobility by independent observers. SETTING: Clinical and outpatient departments of Neurology of the University Medical Centre, Amsterdam. PATIENTS AND METHOD: In 35 patients of the clinical and 25 patients of the outpatient department the stroke disabilities were assessed independently by three observers. The Barthel Index was evaluated in terms of score agreements, homogeneity, and construct validity. RESULTS: There was an excellent concordance of total scores (mean kappa = 0.88; range 0.85-0.90) and single item scores (range mean values of kappa = 0.82-1.00). Repeated analyses, after exclusion of patients with maximum total scores, did not result in a significant reduction of these kappa values. The Barthel Index was a highly homogeneous scale (Cronbach's alpha = 0.96). All items contributed to this reliability in a balanced way. Factor analysis showed that the items on the scale described one common underlying trait. This factor explained 81% of the score variance. CONCLUSION: The Barthel Index is a sound instrument to measure disabilities in ADL and mobility. The scale is suitable for use in both patient care and research. PMID- 8492837 TI - [Intracranial hemorrhage following use of MAO inhibitor tranylcypromine and beer]. AB - A case is reported of non-fatal acute cerebral haemorrhage in a 47-year-old female who was taking tranylcypromine and who drank 500 ml of normal beer. Since the tyramine contents of several beers, including low alcohol and alcohol free beer, are similar, it is recommended that patients taking tranylcypromine should avoid all kinds of beer. PMID- 8492838 TI - [Financing of health research. The Dutch Asthma Foundation]. PMID- 8492839 TI - [Number of admissions for Reiter's disease (ICD-9-code 099.3) in Dutch hospitals in the period 1981-1987]. PMID- 8492840 TI - [Prenatal treatment of allo-immune thrombocytopenia using high-dose IgG]. PMID- 8492841 TI - [Controversies in preventive health care. III. Child health care]. PMID- 8492843 TI - [Acute reflex dystrophy]. PMID- 8492842 TI - [Metastases in the thyroid gland as cause of thyroid swelling]. PMID- 8492844 TI - Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. AB - To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492845 TI - Esthesioneuroblastoma: prognosis and management. AB - Forty-nine patients with esthesioneuroblastoma were treated at the Mayo Clinic between 1951 and 1990. Their clinical manifestations and treatment results were reviewed to identify possible prognostic factors. The 5-year survival rate for all patients was 69%. Tumor progression occurred in 25 patients (51%; no local control in 6 and local recurrence in 19). Metastasis was found in 15 patients (31%; regional in 10 and distant in 9). Nineteen patients died directly from metastatic or intracranial tumor extension. The pathological grade of the tumor was the most significant prognostic factor identified. The 5-year survival rate was 80% for the low-grade tumors and 40% for the high-grade tumors (P = 0.0001). Surgical treatment alone is effective for low-grade tumors if tumor-free margins can be obtained. Radiation is used for low-grade tumors when margins are close, for residual or recurrent disease, and for all high-grade cancers. The poor prognosis associated with high-grade tumors may also mandate the addition of chemotherapy. Recurrent tumor and regional metastasis should be treated aggressively because this approach has been shown to be worthwhile. A craniofacial resection is now the surgical procedure performed in all cases. Because recurrence can occur after 5 or even 10 years, long-term follow-up is mandatory. PMID- 8492846 TI - Primary leptomeningeal melanoma: an unusually aggressive tumor in childhood. AB - Primary malignant melanoma of the leptomeninges of the central nervous system is a rare and aggressive tumor in children. We report our experience from 1964 to 1990 with this tumor in eight children. The mean age at diagnosis was 4.9 years (range, 1.3 to 13 yr). Five children presented with signs and symptoms of raised intracranial pressure from hydrocephalus secondary to tumoral obliteration of the basal cisterns, but the time from the initial symptomatology to diagnosis was frequently delayed. Three patients in this series had hairy nevi in association with their leptomeningeal melanoma. Cerebrospinal fluid (CSF) analysis typically showed raised opening pressures, decreased glucose, and increased protein concentrations. Malignant melanoma cells were found in the CSF in three patients. Confirmatory radiographic examinations included air encephalography, myelography, and computed tomographic and magnetic resonance scanning. Four patients were treated with lumboperitoneal shunts, and one patient was treated with a ventriculoperitoneal shunt for hydrocephalus. Two patients underwent craniotomies and subtotal excisions of their tumors. In seven patients, a definitive diagnosis of leptomeningeal melanoma was made by pathological examination of tissues sent at surgery or at post mortem. In one case, the diagnosis was established by a detailed cytological analysis of the CSF. Four children died of fulminant disease and tumor spread before treatment could be instituted. The four children who received treatment had a combination of radiation therapy and chemotherapy. One child received intrathecal methotrexate. The two children with the longest survivals (2 and 3 yr, respectively) received cisplatinum and dimethyltriazenoimidazole carboxamide in addition to craniospinal irradiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492847 TI - Factors predisposing to clinical disability in patients with cavernous malformations of the brain. AB - The factors predisposing to an aggressive clinical course in cavernous malformations of the brain are not known. Disabilities from neurological deficits and from seizures were assessed and graded in 84 patients harboring 100 cavernous malformations and were correlated with patient sex and age, lesion size, lesion location, lesion multiplicity, and previous overt hemorrhage. Univariate analysis showed that female sex, infratentorial lesion location, and previous gross hemorrhage were significantly associated with subsequent neurological disability. Logistic regression analysis showed that infratentorial lesion location and previous gross hemorrhage were independent factors simultaneously and significantly associated with neurological disability. Age less than 40 was the only significant factor predisposing to seizure disability (in both univariate and multivariate analyses). Lesion size, multiplicity, and other factors did not influence clinical disability. This information should assist in management decisions regarding cavernous malformations. PMID- 8492848 TI - Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. AB - Forty-five measurements of diameters of 12 human cerebral arteries were performed during 10 craniotomies under moderate changes in mean blood pressure and end tidal CO2. The mean change in blood pressure was 30 +/- 16 mm Hg (standard deviation) and that of end tidal CO2 was 14 +/- 6 mm Hg (standard deviation). These changes were induced with nitroprusside, phenylephrine, and adjustment of ventilator rate. Measurements were made through the operating microscope focused at the highest power, with meticulous attention to constant angle and distance from the artery. The mean diameter change in the large cerebral arteries (carotid, middle cerebral artery, vertebral artery) was less than 4%, but the smaller arteries (anterior cerebral artery, M2 segment of middle cerebral artery) showed diameter changes as large as 29% and 21% to end tidal CO2 and blood pressure changes, respectively. These data suggest that at the time of craniotomy, diameters of the large cerebral vessels do not significantly change during moderate variations in blood pressure and CO2, but that larger changes may occur in smaller vessels. This constancy of diameter suggests that the transcranial Doppler velocities obtained during intraoperative monitoring of craniotomies may closely reflect blood flow through the insonated artery. PMID- 8492849 TI - Cauda equina syndrome secondary to lumbar disc herniation. AB - Between 1986 and 1991, 14 patients (nine men and five women), ranging in age from 22 to 67 years (mean, 43 yr), presented with acute cauda equina syndrome from a herniated lumbar disc. All presented with bilateral sciatica and leg weakness; 13 (93%) had urine or stool incontinence, or both. At presentation, all were emergently studied with myelogram/computed tomographic or magnetic resonance imaging. Nine (64%) had large or massive herniations, including two with tethered cords. Five had smaller herniations superimposed on preexisting stenosis. Three had previous surgery; two-thirds had a herniation at a different level. The levels of the herniations were L4-L5 in nine patients, L5-S1 in three patients, and L3-L4 in two patients. The time to surgery ranged from less than 24 hours to more than 30 days; 11 patients underwent surgery within 5 days of onset. Follow up ranged from 6 months to 5 years (mean, 3.3 yr). Postoperatively, six patients (44%) were normal, four (28%) had chronic pain and numbness, and four (28%) had persistent incontinence and weakness. All the patients were ambulatory. There were no operative deaths, and only one patient had a wound infection. Of the 10 patients who had no incontinence after surgery, 7 underwent surgery within 48 hours of onset. Of the four patients with persistent incontinence, all underwent surgery after 48 hours. Previous reports and our experience demonstrate the following most common characteristics for this presentation: 1) male sex; 2) L4 L5 herniations; and 3) onset in the 4th decade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492850 TI - Anatomical basis of syringomyelia occurring with hindbrain lesions. AB - Hindbrain lesions that distort or compress the cervicomedullary junction are commonly associated with syringomyelia. As a basis for discussing pathogenetic mechanisms, the upper end of the central canal of the spinal cord was examined histologically in six aborted fetuses and 14 adults dying of natural causes; the results were correlated with magnetic resonance images in 40 normal subjects. The central canal of the medulla, which extends from the cervicomedullary junction to the fourth ventricle, was found to migrate dorsally, elongate in dorsoventral diameter, and dilate beneath the tip of the obex to form a large, everted aperture. This opening communicates directly with the subarachnoid space through the foramen of Magendie and is indirectly continuous with the main body of the fourth ventricle. In adults, the aperture of the central canal is located approximately 1.0 cm below the tela choroidea inferior and 3.5 cm below the midpoint of the fourth ventricle. Analysis of magnetic resonance imaging scans in 45 patients with syringomyelia and simple hindbrain lesions revealed two patterns of cavity formation: 1) lesions that obstructed the upper end of the central canal or its continuity with the subarachnoid space produced a noncommunicating type of syringomyelia; and 2) lesions that obstructed the basilar cisterns or the foraminal outlets of the fourth ventricle produced a communicating type of syringomyelia (hydromyelia) in association with hydrocephalus. Evidence is presented that syrinxes occurring with hindbrain lesions are not caused by a caudal flow of cerebrospinal fluid from the fourth ventricle into the central canal of the spinal cord. PMID- 8492851 TI - Sacral agenesis and caudal spinal cord malformations. AB - Thirty-three children and one adult with sacral agenesis (SA) were studied by computed tomographic myelography and/or magnetic resonance imaging and were monitored for a mean period of 4.7 years. Four children had the OEIS (concurrent omphalocele, cloacal exstrophy, imperforate anus, and spinal deformities) complex, and three others had VATER (vertebral abnormality, anal imperforation, tracheoesophageal fistula, and renal-radial anomalies) syndrome. All patients shared some of the characteristic features of SA, namely, a short, intergluteal cleft, flattened buttocks, narrow hips, distal leg atrophy, and talipes deformities. Neurologically, lumbosacral sensation was much better preserved than the motor functions, and urinary and bowel symptoms were universal. The level of the vertebral aplasia was correlated with the motor but not with the sensory level. The important neuroimaging findings of SA were as follows: 1) 12 patients (35%) had nonstenotic, tapered narrowing of the caudal bony canal, and 2 patients had hyperostosis indenting the caudal thecal sac; 2) 16 patients (47%) had nonstenotic, tapered narrowing and shortening of the dural sac, but 3 patients (9%) had true, symptomatic dural stenosis, in which the cauda equina was severely constricted by a pencil-sized caudal dural sac; 3) the coni could be divided into those ending above the L1 vertebral body (Group 1, 14 patients) and those ending below L1 (Group 2, 20 patients). Thirteen of 14 Group 1 coni were club or wedge shaped, terminating abruptly at T11 or T12, as if the normal tip was missing. All 20 Group 2 coni were tethered: 13 were tethered by a thick filum; 2 were extremely elongated and had a terminal hydromyelia; 3 were terminal myelocystoceles; and 2 were tethered by a transitional lipoma. High blunt coni were highly correlated with high (severe) sacral malformations (sacrum ending at S1), but low-lying tethered coni were highly correlated with low sacral malformations (S2 or lower pieces present).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492852 TI - Clinical investigation of lumbar epidural pressure. AB - To evaluate the usefulness of measuring lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 12 patients with high intracranial pressure after neurosurgical procedures. ISEDP was measured with a Gaeltec catheter-tip pressure transducer placed percutaneously in the lumbar epidural space with a Touhy needle. ICEDP was determined by the conventional method. During the measurement, some manipulations were carried out. ISEDP and ICEDP measurements exhibited a linear correlation. In all but one patient with normal cerebrospinal fluid, ISEDP was 84 to 100% of ICEDP. In patients with mild subarachnoid hemorrhage, ISEDP was 82 to 86% of ICEDP. In patients with severe subarachnoid hemorrhage, ISEDP was 45 to 57% of ICEDP and always fluctuated in parallel with ICEDP. ISEDP accurately reflected ICEDP in response to manipulations such as breath holding, neck compression, compression at the cranial defect, mannitol administration, and coughing. These data suggest that ISEDP measurement is useful in monitoring intracranial pressure in patients with intracranial hypertension. In addition, the measurements can be obtained easily and safely. PMID- 8492853 TI - Reconstruction of skull defects in children and adolescents by the use of fixed cranial bone grafts: long-term results. AB - This article presents the long-term results of skull defect reconstruction in a series of 27 children studied between 1986 and 1990 (mean age, 8.4 yr; range, 1 17 yr). Causes of their defects were encephalocele (six patients), trauma (seven patients), tumor (eight patients), fibrous dysplasia (two patients), postsynostectomy defects (two patients), osteomyelitis (one patient), and Reye's syndrome with bone flap loss (one patient). All patients underwent clinical and computed tomographic scan documentation of their skull defects before and immediately after surgery and at least 1 year later. The average preoperative defect surface area measured 33 cm2 (range, 2.5-114 cm2). Skull defects were reconstructed in all patients with fixed autogenous cranial bone grafts. In the initial five patients, the grafts were fixed with interosseous wires, and in the remainder, they were fixed with a combination of miniplates and microplates and screws. Follow-up ranged from 12 to 66 months (mean, 31.4 mo). Complications were minimal, with no infection, plate or graft exposure, or intracranial injuries. In 24 of 27 patients, clinical examination and computed tomographic scans showed no evidence of skull defect or appreciable irregularity of donor or recipient sites. Two patients had documented small regions of graft resorption. One skull had palpable contour irregularities but without a bony defect. All patients have resumed routine activities and sports without special head protection. Repair of skull defects in children with fixed autogenous cranial grafts is a reliable method of reconstruction with minimal morbidity. Although we prefer miniplates and microplates and screws for fixation, the grafts fixed in place with interosseous wires did equally well. PMID- 8492854 TI - Carotid microendarterectomy. AB - The illumination and magnification provided by the operating microscope allow for the accurate and complete removal of atherosclerotic plaque from the carotid arterial wall, for precise arterial repair at the distal end of the internal carotid endarterectomy, and for a fine, nonstenosing arteriotomy closure. A high dissection of the internal carotid artery, allowing arterial exposure above the plaque, is particularly helpful in the performance of carotid microendarterectomy. The technique of carotid microendarterectomy has been used in a consecutive series of 60 patients with symptomatic carotid stenosis, all but 5 of whom had carotid stenoses of 70% or more. In this series, there were no deaths and only one postoperative stroke, due to occlusion at the operative site. Emergency thrombectomy and angioplasty restored blood flow, and the patient recovered. In this and all other patients, carotid patency after surgery has been confirmed (angiography in 6 and Doppler examination in 54). Although postoperative stroke risk is dependent upon many factors, we feel that the refinements afforded by the operating microscope help reduce the risks associated with surgical technique to a minimum. PMID- 8492855 TI - Stereotactic radiosurgery: at the threshold or at the crossroads? AB - More than 15,000 patients worldwide have undergone stereotactic radiosurgery since the technique was first described in 1951. Over 6000 of these patients had arteriovenous malformations, usually relatively small. Increasingly, patients with benign and malignant brain tumors have had radiosurgery as an alternative to microsurgical removal. The role of radiosurgery as a tool for functional neurosurgery is being evaluated further. Numerous studies over the past 10 years have examined the benefits and risks of radiosurgery performed with various devices (cyclotron-generated particle beams, the multisource cobalt-60 gamma knife, and modified linear accelerators). As radiosurgical centers continue to proliferate, often without appropriate regulatory review, lamentable lapses in appropriate patient selection, quality assurance, training, and results analysis may ensue. Critical clinical and radiobiological questions (dose, histology, and volume variables) remain to be answered in appropriate studies; these needs can no longer be ignored by governmental funding sources. Stereotactic radiosurgery is a multidisciplinary field, requiring the leadership of neurological surgeons in cooperation with radiation oncologists, radiologists, and medical physicists. For many indications, stereotactic radiosurgery appears poised at both the threshold and at the crossroads. As clinical application progresses, continued dialogue between neurological surgeons and their professional colleagues is necessary to guide proper patient management decisions. PMID- 8492856 TI - An experimental study of cerebrovascular resistance, pressure transmission, and craniospinal compliance. AB - To successfully match the treatment to the cause for raised intracranial pressure (ICP) after a severe head injury, it is important to know the underlying mechanism at a given moment for the raised pressure. In particular, it is important to distinguish between active cerebral vasodilation, indicating functional autoregulation, and a passive vascular dilation as the cause for raised ICP. An experimental study was performed in feline models of diffusely raised ICP (n = 6), of active arterial vasodilation caused by arterial hypercarbia (n = 6), and of passive arterial dilation caused by pharmacologically induced arterial hypertension (n = 6) to determine if wave form analysis of ICP can distinguish active from passive arteriolar vasodilation. Pulsatile pressure transmission from the blood pressure pulse to the ICP pulse (cerebrovascular pressure transmission [CVPT]), cerebrovascular resistance, and craniospinal compliance were measured simultaneously at each level of raised ICP, arterial hypercarbia, and arterial hypertension. Arterial hypercarbia, caused by both 5 and 10% inspired CO2 increased low-frequency CVPT, which was followed by an increasingly negative phase shift between the blood pressure and ICP wave form (P < 0.05). Diffusely raised ICP caused by intraventricular infusion of mock cerebrospinal fluid caused increased low-frequency CVPT (P < 0.01) but resulted in no overall change in phase shift, although the sign of the phase shift remained negative. After arterial hypertension, caused by the infusion of angiotensin II, where there was loss of myogenic tone, an increased low-frequency CVPT was accompanied by a positive phase shift (P < 0.01). These data demonstrate it may be possible to distinguish active arteriolar vasodilation from a passive loss of autoregulatory vascular tone through simultaneous measurement of the low frequency CVPT and phase shift. Analysis of the ICP wave form provides information relevant to the management of raised ICP. PMID- 8492857 TI - Experimental investigation of lumbar epidural pressure measurement. AB - To evaluate the usefulness of lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 25 adult mongrel dogs. ICEDP and ISEDP were measured simultaneously with Gaeltec catheter tip pressure transducers placed in the parietal epidural space and in the lumbar epidural space. Groups 1 and 2 dogs served as normal cerebrospinal fluid condition models. Group 1 received sequential steady-state normal saline infusions (0.5, 1.0, and 1.5 ml/min) into the cisterna magna. ISEDP and ICEDP measurements exhibited a linear correlation, and ISEDP was 80 to 90% of ICEDP at any pressure level. There was no significant difference in the pressure curves obtained at the different infusion rates. Group 2 dogs were subjected to rapid pressure changes by a cisternal bolus injection. Although compliance calculated from the change in ISEDP was slightly greater than that from ICEDP at resting pressure, the compliance calculated from both ISEDP and ICEDP decreased at 20 and 30 mm Hg of ICEDP and the values became almost equivalent. Groups 3 and 4 dogs were mild and severe experimental subarachnoid models, respectively. The ISEDP and ICEDP measurements also showed a linear correlation; however, ISEDP was about 70% of ICEDP in Group 3 and about 50% of ICEDP in Group 4. Although there are varying degrees of discrepancy between ISEDP and ICEDP in the normal or subnormal pressure range and in the presence of severe spinal block, our findings suggest that ISEDP measurements can be used to estimate intracranial pressure in a clinical practice. PMID- 8492858 TI - Parasympathetic cerebrovascular innervation: an anterograde tracing from the sphenopalatine ganglion in the rat. AB - To elucidate parasympathetic cerebrovascular innervation of the rat sphenopalatine ganglion (SPG), we injected wheat germ agglutinin-conjugated horseradish peroxidase into the SPG of one side and traced anterogradely labeled nerve fibers. Three days after the injection, the animals were killed and tissues including the SPG, major cerebral arteries, and ethmoidal arteries were reacted by the tetramethylbenzidine method. A number of cells and nerve fibers labeled with wheat germ agglutinin-conjugated horseradish peroxidase were observed in the SPG. The nasal mucous membrane, the periorbital soft tissue, and the lacrimal gland of the injected side contained numerous labeled nerve fibers. In cerebral vessels, anterogradely labeled nerve fibers were observed around the internal ethmoidal, anterior cerebral, middle cerebral, internal carotid, and posterior cerebral arteries of both sides. A few labeled nerve fibers were seen on the wall of the basilar arteries of the distal portion, and the vertebral arteries contained no labeled nerve fiber. In animals of which the ethmoidal nerve and the external ethmoidal artery were cut together with the surrounding periorbital soft tissues just before entering the ethmoidal foramen, no labeled nerve fiber was identified on the wall of the major cerebral arteries. Although labeled gangliocytes were found in the trigeminal and superior cervical ganglia after the tracer injection to the ipsilateral SPG, the chronic maxillary neurotomy and superior cervical ganglionectomy did not alter the distribution of the labeled nerve fibers on the wall of the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492859 TI - 100 years ago in neurosurgery: description of the intracranial extradural approach to the Gasserian ganglion--the Hartley-Krause operation. PMID- 8492860 TI - A case of distal anterior choroidal artery aneurysm: case report and review of the literature. AB - We describe a very rare case of distal anterior choroidal artery aneurysm. A 34 year-old woman was admitted to our hospital because of headache and vomiting. Computed tomographic scans revealed a diffuse intraventricular hematoma and a thin subarachnoid hemorrhage. Cerebral angiography disclosed a saccular aneurysm in the peripheral portion of the right anterior choroidal artery, which was located in the temporal horn of the right lateral ventricle. We approached the temporal horn through a small inferior temporal incision, and the aneurysm was resected without any neurological damage. A histological examination of the surgical specimen revealed it to be a true aneurysm. PMID- 8492861 TI - Striatal glucose metabolism and [18F]fluorodopa uptake in a patient with tumor induced hemiparkinsonism. AB - We studied a patient with a falx meningioma in the right supplementary motor area and a left-sided hemiparkinsonism that resolved after the tumor was removed. Because there was no evidence of distortion of the basal ganglia and midbrain by the tumor on neuroradiological examination, the possible mechanism of parkinsonism is an impairment of the basal ganglia output to the supplementary motor area. Positron emission tomography scans with 2-[18F]fluoro-2-doxy-D glucose and 6-L-[18F]fluorodopa were performed to measure regional cerebral glucose metabolism and striatal dopamine metabolism, respectively. Regional cerebral glucose metabolism was decreased in the striatum of the side of the lesion, although dopamine metabolism was normal. These data suggest that the tumor may have impaired synaptic function of the striatum as a whole, giving rise to contralateral hemiparkinsonism without an impairment of the presynaptic dopaminergic nerve terminals in the striatum. PMID- 8492862 TI - Arachnoid cyst of the lateral ventricle manifesting positional psychosis. AB - A 30-year-old woman had an arachnoid cyst in the trigone of the right lateral ventricle 5 years before she developed episodic auditory and visual hallucinations as well as delusions of persecution. The psychotic episodes tended to occur after the patient had lain in bed for 1 to 2 hours. After craniotomy and wide excision of the cystic membrane, draining the cystic fluid to the lateral ventricle, the psychotic episodes subsided in a follow-up period of 6 months. We believe that when the patient was recumbent, the trigone cyst blocked the temporal horn further, caused local ischemia, and triggered the psychosis, which was a form of partial complex psychomotor seizure. PMID- 8492863 TI - Paragangliomas of the sellar region: report of two cases. AB - Two cases of paraganglioma arising from the parasellar region are presented. Both occurred in middle-aged women who sought treatment of headaches but who had no endocrinological dysfunction; one case was associated with ophthalmoplegia from cavernous sinus involvement. Diagnosis in both cases was confirmed by typical histological appearance and cytochemical demonstration of immunoreactive chromogranin in tumor cells. The pathological features and possible pathogenesis of parasellar paragangliomas are discussed. PMID- 8492864 TI - Giant cell tumor of the orbit. AB - Giant cell tumors of the skull are very rare and usually occur in the sphenoid bone. The authors report the case of a 10-year-old boy with such a tumor involving exclusively the roof of the left orbit. He presented essentially with edema of the left superior eyelid and diplopia. Computed tomographic examination and magnetic resonance imaging delineated the lesion, which was radically removed via a left fronto-orbital craniotomy. Some aspects of this rare neoplasm are reviewed. PMID- 8492865 TI - Treatment of a bacterial (mycotic) intracranial aneurysm using an endovascular approach. AB - The case of a patient with a bacterial intracranial aneurysm treated with antibiotics and endovascular obliteration is reported. The patient presented with dysphasia and right hemiparesis. A medical workup revealed endocarditis and associated heart valve dysfunction with no evidence of congestive heart failure. Computed tomography demonstrated subarachnoid hemorrhage, and a subsequent cerebral arteriogram showed a distal left middle cerebral aneurysm, which, as demonstrated by angiography, did not change in size in 2 weeks. An endovascular approach was used to obliterate the aneurysm and its parent vessel. Endovascular techniques may be used to obliterate certain bacterial intracranial aneurysms, particularly in patients who harbor distal aneurysms. PMID- 8492866 TI - Third ventriculostomy for shunt infections in children. AB - Four children with extracranial shunts for noncommunicating hydrocephalus suffered from recurrent or intractable shunt infections. All patients were resistant to or relapsed after treatment with intravenous and intrathecal antibiotics with change of the shunt apparatus. They were treated with neuroendoscopic third ventriculostomy and the removal of all implants, except for a reservoir in one patient. That child later had the reservoir removed because of persistent proteus infection. All patients received antibiotics for approximately 2 weeks after the operation. There was no morbidity associated with the procedure, and all patients remain shunt independent with follow-up periods of 21 to 46 months (mean, 33 mo), although one has needed another third ventriculostomy. We have shown that third ventriculostomy is a successful surgical intervention for the management of shunt infections in patients with noncommunicating hydrocephalus. PMID- 8492867 TI - Physiological localization of the facial colliculus during direct surgery on an intrinsic brain stem lesion. AB - We designed a method for localizing facial colliculus intraoperatively by means of weak stimulation of the 4th ventricular floor and recording the electromyographic response of the facial muscle. This method is applicable clinically to prevent 6th and 7th cranial nerve complications during direct surgery on an intrinsic lesion of the brain stem, in which the normal anatomy of the rhomboid fossa is often distorted. PMID- 8492868 TI - "Transinsular approach" for the treatment of a medial temporal arteriovenous malformation. AB - A new approach for the treatment of arteriovenous malformations in the medial temporal lobe is proposed. This approach, referred to as the "transinsular approach," comprises incising the superior part of the anterior insula and exploring the plexal point of the anterior choroidal artery through the space between the dissected insula and the frontal lobe. A representative case of a patient with a large medial temporal arteriovenous malformation that was successfully extirpated by this approach is reported. The advantages of this approach and the functional results of partial incision of the insula are discussed. PMID- 8492869 TI - Two simple devices for microneurosurgery: automatic drip irrigating needle and a suction retractor. AB - During microneurosurgical procedures, frequent intermittent irrigation and/or suction are often necessary. We describe two simple devices: the automatic drip irrigating needle and the suction retractor. We have confirmed their usefulness through our routine use of these simple devices since 1982. PMID- 8492870 TI - Comparison of the clinical presentation of symptomatic arteriovenous malformations (angiographically visualized) and occult vascular malformations. PMID- 8492871 TI - Summary: vestibular schwannoma (acoustic neuroma) consensus development conference. PMID- 8492872 TI - Outcome analysis in 654 surgically treated lumbar disc herniations. PMID- 8492873 TI - Evaluation of a program to prevent head and spinal cord injuries: a comparison between middle school and high school. PMID- 8492874 TI - Double dissociation of spatial and object visual memory: evidence from selective interference in intact human subjects. AB - A functional dissociation of the spatial and object visual systems was produced by selective interference in intact young adults. Subjects were instructed to remember the location of a dot in a spatial memory test, and the form of an object memory test. As predicted by current notions of dissociable visual systems in the primate, spatial memory was selectively impaired by a movement discrimination spatial task, whereas object memory was selectively impaired by a color discrimination object task. PMID- 8492875 TI - Effect of unilateral temporal-lobe excision on perception and imagery of songs. AB - Auditory imagery for songs was studied in two groups of patients with left or right temporal-lobe excision for control of epilepsy, and a group of matched normal control subjects. Two tasks were used. In the perceptual task, subjects saw the text of a familiar song and simultaneously heard it sung. On each trial they judged if the second of two capitalized lyrics was higher or lower in pitch than the first. The imagery task was identical in all respects except that no song was presented, so that subjects had to generate an auditory image of the song. The results indicated that all subjects found the imagery task more difficult than the perceptual task, but patients with right temporal-lobe damage performed significantly worse on both tasks than either patients with left temporal-lobe lesions or normal control subjects. These results support the idea that imagery arises from activation of a neural substrate shared with perceptual mechanisms, and provides evidence for a right temporal-lobe specialization for this type of auditory imaginal processing. PMID- 8492876 TI - Is a dot-filling group test a good tool for assessing manual performance in children? AB - A dot-filling test was used to assess hand performance in two populations of French children. In the first experiment, the effect of sex, age and handedness on hand performance was examined (1742 children). Age was related to the degree of laterality, but girls were less lateralized than boys. The second experiment (200 children) showed that the surprising sex differences cannot be explained by the group testing procedure. Underlying processes leading to performance in the dot-filling task are probably different from those involved in other tests generally used for children. PMID- 8492877 TI - Time for reorienting of attention: a premotor hypothesis of the underlying mechanism. AB - The paradigm of the covert orienting of attention (COA) has shown that the displacement of visual attention may be assessed even in the absence of eye movement. Stimuli correctly cued before their presentation are usually detected faster than uncued stimuli. However, miscued stimuli induce an increased detection time, which has been attributed to the time required for the reorientation of attention from the incorrect to the correct spatial location. Currently, the mechanism of such a displacement of visual attention remains unknown. Rizzolatti et al. Neuropsychologia 25, 31-40 (1987) have suggested a premotor hypothesis which suggests that an oculomotor disprogramming and reprogramming is necessary to reorient visual attention, even if the eye movement is inhibited. Since shifting of auditory attention from one ear to the other does not require any motor control, we further investigated the model of COA in 20 normal subjects who performed two tasks requiring a reorienting of auditory attention: (1) a choice RT task that requires a response readjustment during the auditory reorienting; (2) a simple RT task that does not require a response readjustment during the auditory reorienting; (2) a simple RT task that does not require a response readjustment during the auditory reorienting. Results indicate that correctly cued stimuli significantly reduce the RT in both tasks and that this reduction is greater in the choice than in the simple RT task. This suggests that a correct cue may produce a pre-programming of the response, in addition to the pre-engagement of the perceptual attention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492878 TI - The drawing of objects by a visual form agnosic: contribution of surface properties and memorial representations. AB - Although edge-based representations of objects are thought to play a central role in object identification, it is clear that real objects convey more information about their form than line drawings. Patients with visual form agnosia, for example, are able to identify real objects more easily than the corresponding line drawings of those objects, even if exactly the same projection planes are used [Goodale et al. Object versus picture identification in a patient with visual form agnosia. Paper presented at the annual meeting of the Association for Research in Vision and Ophthalmology (April, 1991). Sarasota, FL, 1991]. To compare these two modes of representation in another way, we asked a patient (D.F.) with profound visual form agnosia to make line drawings of a series of common objects, either from long-term memory, from the real objects themselves, or from line drawings of those objects. When four independent judges rated the drawings as to how well they represented the target objects, drawings from memory received higher ratings than drawings of real objects which in turn received higher ratings than those based on line drawings. These results complement those of Goodale et al. (1991) and suggest that cues derived from surface properties and depth can assist in the demarcation of the critical features necessary for the accurate portrayal of objects. They also suggest that despite D.F.'s perceptual deficits, her long-term representation of objects is relatively intact. PMID- 8492879 TI - Displacement of the egocentric visual midline in altitudinal postchiasmatic scotomata. AB - Vertical and horizontal bar bisection was assessed in six patients with homonymous altitudinal scotomata, four of whom had additional hemianopic scotomas. Analysis of performance showed a small but significant deviation of the bisection midline ("egocentric midline") to the upper field in four patients with blindness of the upper hemifield and a more pronounced deviation to the inferior hemifield in two patients with lower altitudinal field defects. In addition, horizontal bar bisection showed a shift of the egocentric midline towards the scotoma in all four patients with left- or right-sided homonymous hemianopia. Hence, location of the scotoma predicted direction of the shift of the egocentric midline but not degree of shift. PMID- 8492880 TI - Egocentric reference and asymmetric perception of space. AB - Normal dextrals performed tactilo-kinesthetic bisection tasks in a median position, at three directions of gaze: 30 degrees to the left, 30 degrees to the right, 0 degree. Instead of pseudoneglect phenomenon, a deviation of the subjective middle to the side opposite to the direction of gaze and hand use was found, whichever hand was used. The results are interpreted in terms of displacement of the position of the egocentric reference and are discussed with respect to activation theory. It is argued that pseudoneglect is part of a more general asymmetric perception of space phenomenon which depends on the position of the egocentric reference. PMID- 8492881 TI - Anomalous sensations following prolonged tactile stimulation. AB - Animal studies have demonstrated that tactile experience can alter central organization of somatosensory information. The present study examined the effect of prolonged tactile stimulation on spatial sensitivity in human subjects. Four subjects received repetitive, tactile stimulation presented on the volar surface of the forearm. The tactile stimuli were delivered through small vibrators worn by the subjects. After a period of 5-9 weeks of wearing the vibrators, three of the four subjects reported anomalous sensations when attempting to localize tactile stimuli. Subjects had difficulty in localizing stimuli and reported sensations of pressure and diffuseness. Single stimuli would sometimes evoke double and triple sensations separated by as much as 20 cm. After removing the vibrators, subjects continued to report anomalous sensations for up to 15 weeks. These results are interpreted within the framework of a model of central, neural reorganization. PMID- 8492882 TI - Active and passive activation of left limbs: influence on visual and sensory neglect. AB - A case of severe left visual neglect who had previously shown reductions in visual neglect with left hand movements in left hemispace showed the same phenomenon when the experiment was repeated, but failed to show it when the left hand was moved passively. However, neglect did reduce when he moved his left leg. Sensory extinction was not affected by left hand movements. Finally, hand movements in left hemispace also reduced neglect for stimuli in far as well as in peripersonal space. These results confirm the close link between visual attention and motor function and provide further support for the idea that contralesional limb movements may reduce visual neglect, possibly by activating a poorly attended body schema which in turn activates corresponding areas of extrapersonal space in at least two spatial systems (reaching and far space, respectively). PMID- 8492883 TI - Handedness in native Amazonians. AB - A sample of 65 Tucano adolescents living in the Amazon region of Colombia were administered a 26-item handedness questionnaire. All subjects were right-handed. A factor analysis of the data indicated a factor structure rather different from that seen in North Americans, although both skilled and unskilled handedness factors were seen. Other factors related to specific tool use and to strength. These data indicate that positive reinforcement for right-hand use can modify patterns of handedness, and may well alter the relations among different items. The data suggest that hand preference can be modified through positive reinforcement at an appropriate age, and that hand preference is the precursor of skill differences rather than vice versa. PMID- 8492884 TI - CT and MRI of haemorrhage into intracranial neuromas. AB - Six patients with haemorrhage into intracranial neuromas were studied by computed tomography (CT) and magnetic resonance imaging (MRI) at 0.5 T with spin-echo pulse sequences. The nature of the tumour and the presence of a haematoma were confirmed by surgery and microscopic examination in all cases. Four neuromas arose from the acoustic nerves and two from the trigeminal. Four of the six patients suffered from sudden onset or rapid worsening of symptoms including headache, vertigo and/or hemifacial motor and sensory disturbances. CT in the acute stage revealed a hyperdense area or a fluid-fluid level (FFL). The hyperdense area disappeared on CT repeated in the chronic stage. On MRI in subacute and chronic stages the haemorrhage showed hyperintensity on both T1 and T2 weighting in five cases examined between 16 and 46 days after the onset, and isointensity on T1 weighting and an FFL on T2 weighting in one case examined 12 days after the onset of symptoms. A well-defined low intensity rim indicating prior haemorrhage was observed on T2-weighted images in three cases. MRI was more effective than CT in detecting haemorrhage into the tumours and in staging it. PMID- 8492885 TI - Pineal cyst: normal or pathological? AB - Review of 500 consecutive MRI studies was undertaken to assess the frequency and the appearances of cystic pineal glands. Cysts were encountered in 2.4% of cases. Follow-up examination demonstrated no change in these cysts and they were considered to be a normal variant. Size, MRI appearances and signs associated with this condition are reported in order to establish criteria of normality. PMID- 8492886 TI - MRI detection of ruptured malignant teratoma in the third ventricle. PMID- 8492887 TI - MRI of a dermoid cyst containing hair. AB - A fourth ventricular dermoid cyst examined by CT, MRI and angiography is reported. The combination of CT density and MRI signal indicated the presence of hair within the cyst, which was confirmed at surgery. PMID- 8492888 TI - Imaging of large Rathke's cleft cysts by CT and MRI: report of two cases. AB - Two patients with large Rathke's cleft cysts in the sella turcica and suprasellar region presented with visual impairment and hypopituitarism. The entirely different CT and MRI appearances of the two cysts were thought to depend principally on the protein content of the cyst fluid. PMID- 8492889 TI - Recurrent craniopharyngioma invading the orbit, cavernous sinus and skull base: a case report. PMID- 8492890 TI - Gadolinium-enhanced MRI in a patient with AIDS and the Ramsay-Hunt syndrome. PMID- 8492891 TI - "Dural tail" adjacent to acoustic neuroma on MRI: a case report. AB - A "dural tail" on Gd-DTPA-enhanced MRI has been often observed adjacent to meningiomas and considered to be useful in distinguishing meningioma of the cerebellopontine angle from acoustic neuroma. However, demonstration of a dural tail adjacent to an acoustic neuroma indicates that this sign is not specific. PMID- 8492892 TI - Metastatic bronchial adenocarcinoma showing the "meningeal sign": case note. PMID- 8492893 TI - Posterior cranial fossa tumours in childhood. AB - We reviewed clinical and CT findings in 133 posterior cranial fossa tumours in children. All had histological diagnosis, apart from 20 cases of brain stem glioma. The majority were intra-axial tumours, including 53 medulloblastomas (40%), 31 cerebellar astrocytomas (23%), 28 brain stem gliomas (21%), 14 ependymomas (11%), and single cases of ganglioglioma, haemangioblastoma and teratoma. Extra-axial tumours formed only 3%, including 2 chordomas and 2 schwannomas. The clinical data and CT findings are reviewed. Cerebellar astrocytoma involved the sexes equally, while medulloblastoma, brain stem glioma, and ependymoma were more common in males. Most cerebellar astrocytomas were in the midline, and presumably arose from the vermis. The frequency of calcification was similar to that in previous reports, being highest in ependymoma (69%), followed my medulloblastoma (29%), cerebellar astrocytoma (17%), and brain stem glioma (8%). PMID- 8492894 TI - Gliosarcoma of the posterior cranial fossa: MRI findings. AB - We report the MR findings of a biopsy-proven gliosarcoma of the posterior cranial fossa. Multiple homogeneously enhancing lesions had shaggy margins and broad based dural attachments, which may reflect the gliomatous and sarcomatous element of this tumour. PMID- 8492895 TI - A kindred of hereditary adult-onset leukodystrophy with sparing of the optic radiations. AB - We describe a family with hereditary adult-onset leukodystrophy with sparing of the optic radiations, shown clinically, neuroradiologically and electrophysiologically. All five affected members developed their leukodystrophy in their fourth decade and clinical features steadily progressed. The sparing of the optic radiations is not typical of other leukodystrophies. We suggest that this is a new clinical entity. PMID- 8492896 TI - Basal ganglia and white matter in pregnancy-induced hypertension. PMID- 8492897 TI - Subtotal agenesis of the cerebellum in an adult. MRI demonstration. AB - We describe a 58-year-old asymptomatic woman with subtotal developmental absence of the cerebellum. MRI evaluation showed minute remnants of cerebellar tissue corresponding to the anterior quadrangular lobules. These findings identified the anomaly as subtotal cerebellar agenesis, and excluded other diagnostic possibilities. PMID- 8492898 TI - Plain film clues to the diagnosis of spinal epidural neoplasm and infection. AB - Radiographs of 22 normal patients and 35 patients with proven epidural disease were correlated with CT scans to determine the range of normal and abnormal appearances of the osseous surfaces marginating the spinal canal. A subtle but useful plain film clue to early epidural disease was indistinctness of the posterior vertebral body margin, which in at least one case was the solitary radiographic sign of epidural metastasis. The radiographic distinctness of each of the bony margins of the spinal canal varied predictably with spinal level in normal individuals owing to systematic variations in obliquity. Indistinctness of an osseous spinal canal margin, interpreted with knowledge of the range of normal anatomy at the appropriate level, may provide the earliest plain film clue to the presence of spinal epidural disease. PMID- 8492899 TI - Colour Doppler imaging of partial subclavian steal syndrome. AB - The case of a 67-year-old woman with symptoms related to the vertebro-basilar system and blood pressure difference of the upper extremities is presented. Colour-Doppler imaging (CDI) with additional spectral tracing revealed partial subclavian steal syndrome with retrograde flow in the left vertebral artery during systole, which could be significantly enhanced by reactive hyperemia after left arm exercise. Angiography confirmed a high-grade stenosis of the proximal subclavian artery and balloon angioplasty was performed. Noninvasive follow-up by CDI demonstrated regular antegrade vertebral artery flow at rest, but minimal retrograde systolic flow after left arm exercise. PMID- 8492900 TI - Difficulties in examination of the origin of the vertebral artery by duplex and colour-coded Doppler sonography: anatomical considerations. AB - Despite progress in ultrasonographic techniques visualisation of the origin of the vertebral arteries, particularly the left, by duplex and colour Doppler imaging, still poses a problem in a significant number of patients. In anatomical and radiological studies we demonstrated an anomalous origin in 6%, the left vertebral artery originating directly from the aorta in most cases. The origin from the subclavian artery was found to be posterior in 44% and inferior in 6%. The V1 segment of the vertebral artery (from its origin to the entry into the foramen transversarium) was tortuous in 47% of cases. These anatomical variants and variations in the course of the vessel contribute to the nonvisualisation of the origin of the vertebral artery by duplex and colour Doppler imaging. With respect to tortuosities technical modifications for better visualisation are suggested and possible implications for surgery are discussed. PMID- 8492901 TI - The contribution of colour Doppler flow imaging to the study of cerebral haemodynamics in the neonate. AB - We investigated the contribution of colour Doppler flow imaging (CDFI) to duplex ultrasonography of the neonatal brain. In pre- and full-term infants, CDFI facilitated spectral analysis of blood flow velocity wave forms in most major intracranial arteries, enabling blood flow velocity measurements. Moreover CDFI depicted major deep and superficial veins, enabling venous blood flow velocity measurements. Smaller arteries could also be imaged in a substantial number of infants in regions with haemorrhagic or ischaemic lesions. The method may also offer the opportunity to assess regional cerebral blood flow in the neonatal brain, although further study is necessary to determine whether accurate, reproducible flow velocity measurements are possible in these vessels. PMID- 8492902 TI - Delayed angiography in the investigation of intracerebral hematomas caused by small arteriovenous malformations. AB - We reviewed the clinical and radiological features of ten patients with small arteriovenous malformations that caused intracerebral hematomas. In six patients, angiography showed a small nidus (less than 1 cm in diameter) with a shunt at the site of the hematoma, and in four only an early-filling vein was evident. Six patients had only delayed angiography (4 weeks or more after the ictus). In three, angiography within 2 days of the ictus failed to reveal the cause of the bleed, but repeat angiography showed an early-filling vein in two, and a nidus with shunting in one. In only one patient did early angiography reveal the malformation. MRI was obtained in eight patients, and in two prominent vessels were evident in the wall of the hematoma cavity. In investigation of an unexplained intracerebral hematoma, MRI may be useful to exclude a neoplasm or cavernoma, although the latter may be not be evident in the presence of a recent hematoma. We suggest early MRI and angiography for investigation of an unexplained, nonhypertensive intracerebral bleed, with follow-up MRI and delayed angiography if the initial studies fail to reveal the cause. PMID- 8492903 TI - Spinal cord oedema due to venous stasis. AB - Venous hypertension and stagnant hypoxia in the human spinal cord are poorly understood. We report a case in which a partial Brown-Sequard syndrome resulted from obstruction of venous drainage on one side of the spinal cord. Neurological deterioration and eventual recovery paralleled the formation and clearance of oedema. The clinical and MRI findings support the contention that spinal cord injury arising as a result of obstruction to venous outflow occurs primarily in the white matter, spreading secondarily to the grey matter, and observations that obstruction of venous flow in the high cervical spinal cord results in changes in the lower cervical cord. PMID- 8492904 TI - Acquired epidermoid tumour in the thoracic spinal canal. AB - Acquired spinal epidermoid tumours are rare, and probably caused by skin fragments that have been transplanted by trauma or lumbar puncture. They almost always occur in the region of the cauda equina. We present an acquired spinal epidermoid tumour at the T 10 level, with pathological confirmation. A skin fragment had migrated to a site where it developed into a tumour. PMID- 8492905 TI - Headache after lumbar iohexol myelography: the influence of a history of headaches and early ambulation. AB - Whether a history of headache or "early" versus "late" ambulation (no bed rest or bed rest for 24 h) influence the occurrence of headache after lumbar iohexol myelography was studied by blinded interviews in 158 consecutive patients referred for elective lumbar myelography (LM) because of suspected lumbar disc prolapse or spinal stenosis. Headache after LM occurred more often in patients with a history of headache (57%) than in patients without such a history (29%), P < 0.001. Patients with normal myelographic findings complained of headache after LM more often (55%) than patients with abnormal myelograms (31%), P < 0.008. No difference in the incidence of headache after LM was demonstrated in early versus late ambulation. PMID- 8492906 TI - Status epilepticus following iohexol myelography. AB - Iohexol, a contrast medium widely used for myelography, has rarely been reported to cause convulsive disorders. A case of status epilepticus resulting from iohexol myelography is reported and problems of treatment are discussed. PMID- 8492907 TI - Systemic interleukin-1 beta decreases brain-derived neurotrophic factor messenger RNA expression in the rat hippocampal formation. AB - Brain-derived neurotrophic factor is selectively expressed at relatively high levels in the rat hippocampal formation (for review, see Ref. 12; see also Refs 8, 13, 19, 20, 27) where it is thought to be involved in mechanisms of neurodegeneration and/or neural protection related to the plasticity of hippocampal neurons. Functional responses to brain-derived neurotrophic factor appear to be mediated by a tyrosine receptor kinase B with the possible involvement of the p75 low-affinity nerve growth factor receptor protein. Among the many characteristics of Alzheimer's disease is an upregulation of immune mediators in and around senile plaques in Alzheimer's disease. Recently, interleukin-1 has been shown to be detrimental to the long-term survival of embryonic hippocampal neurons in culture. Thus, if the same occurs in vivo, it is possible that the accumulation of interleukin-1 in Alzheimer's disease hippocampus may be responsible for altered hippocampal neuron synaptic plasticity. This may occur either by a direct action of interleukin-1 on hippocampal neurons or possibly indirectly by stimulating beta-amyloid production. Other indirect mechanisms may involve growth or survival factors such as the neurotrophin brain-derived neurotrophic factor which is thought to play an important role in the plastic responses of hippocampal neurons. A recent study showed that brain-derived neurotrophic factor mRNA is selectively decreased in the dentate gyrus in Alzheimer's disease. The reason(s) for the decrease of brain derived neurotrophic factor mRNA is not known, but one possibility may be associated with the enhanced expression of interleukin-1 in the hippocampus of Alzheimer's disease patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492908 TI - Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons. AB - The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man. Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary, at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone, and when administered with growth hormone-releasing hormone has a synergistic effect. In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus. We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation. Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area. PMID- 8492909 TI - Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: cellular and subcellular distribution in the rat forebrain. AB - Antibodies were made to synthetic peptides corresponding to residues 253-367, 757 771 and 877-889 of the published amino acid sequence of the rat brain glutamate receptor GluR1 subunit [Hollmann et al. (1989) Nature 342, 643-648]. The peptides were synthesized both as multiple copies on a branching lysyl matrix (multiple antigenic peptides) and conventional linear peptides using solid-phase synthesis. Rabbits were immunized with these peptides either without conjugation (multiple antigenic peptides) or following coupling to ovalbumin with glutaraldehyde (monomeric peptides). The antibodies from immune sera were then purified by affinity chromatography using reactigel coupled monomeric peptides. All the rabbits produced good antipeptide responses, and were characterized by immunoprecipitation of solubilized alpha-amino-3-hydroxy-5-methylisoxazole-4 propionate and kainate binding activity and by their staining patterns on immunoblots. Antibody to peptide 253-267 specifically immunoprecipitated 12 +/- 3, 50 +/- 3 and 44 +/- 4% of solubilized alpha-amino-3-hydroxy-5-methylisoxazole 4-propionate binding activity from cortex, hippocampus and cerebellum, respectively. Under identical conditions, antibody against the 877-889 peptide removed 23 +/- 4, 9 +/- 4 and 15 +/- 9% of alpha-amino-3-hydroxy-5 methylisoxazole-4-propionate binding sites from these areas. On immunoblots of rat brain membrane samples separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, antibodies labelled a 105,000 mol. wt immunoreactive band. GluR1 was immunoaffinity-purified using subunit-specific antibodies against both N-terminal (253-267) and C-terminal (877-889) residues, covalently attached to protein A-agarose. Analysis of the purified product from each column showed a major immunoreactive band, recognized by both sera at 105,000 mol. wt and silver staining identified the same major protein. After exhaustive immunoprecipitation of solubilized membrane samples with antibody against the C-terminal of the subunit, a subpopulation of GluR1 was labelled with antibodies specific for the N terminal part of the receptor. These observations suggest that the GluR1 subunit consists of at least two isoforms possessing a common N-terminal region but a distinct C-terminus. Immunocytochemistry, using immunoperoxidase staining, was performed for the GluR1 subunit in rat forebrain with antisera raised against the N-terminal (253-267) and the C-terminal parts (877-889) of the molecule. Both antisera gave a similar distribution of immunoreactivity at the light-microscopic level. Immunoreactivity for the GluR1 subunit was selectively distributed throughout the rat forebrain. The hippocampus, septum, amygdala and olfactory bulb exhibited the strongest immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492910 TI - Secretoneurin--a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (chromogranin C). AB - Secretogranin II (chromogranin C), originally described as tyrosine sulfated protein of the anterior pituitary, is present in large dense core vesicles of several endocrine cells and neurons. We raised antisera in rabbits to conjugates of two synthetic peptides (bovine secretogranin 133-151 and rat secretogranin 154 186) flanked in the primary structure of secretogranin II by pairs of basic residues and used them to investigate the proteolytic processing of this protein by immunoblotting and a newly developed radioimmunoassay. The sensitivity of this assay was 30 fmol for secretogranin 154-186 and 60 fmol for secretogranin 133 151. The highest degree of processing of secretogranin II (> 90%) occurs in brain. One of the peptides (secretogranin 133-151) is not generated to any significant extent. The other peptide, secretogranin 154-186, however, is formed in vivo, and in brain the free peptide apparently represents the predominant form. The highest concentrations of secretogranin 154-186 are found in the hypothalamus, two- to six-fold lower levels are present in the hippocampus, caudate nucleus, thalamus and brainstem. These concentrations are comparable to those of established neuropeptides. In order to indicate the special relevance of secretogranin II and of this peptide for brain we have named this peptide secretoneurin. The newly developed radioimmunoassay for this peptide will be a useful tool to establish its physiologic role in brain. PMID- 8492911 TI - Estradiol induces plasticity of gabaergic synapses in the hypothalamus. AB - The number of axosomatic synapses on arcuate neurons of the adult rat hypothalamus fluctuates following the sequence of increasing circulatory estradiol during the ovarian cycle. To determine whether estrogen is affecting GABAergic synaptic contacts we studied the number of GABA-immunoreactive axosomatic synapses in adult ovariectomized rats injected either with 17 beta estradiol (100 micrograms/100 g body weight) or with sesame oil vehicle. The number of immunoreactive axosomatic synapses was significantly reduced in estradiol-treated rats (77 +/- 8 vs 56 +/- 6 synapses per 1000 microns of perikaryal membrane in control and estradiol-treated rats, respectively) while the number of non-immunoreactive synapses was not significantly affected by the hormonal treatment (44 +/- 6 vs 35 +/- 5 synapses per 1000 microns of perikaryal membrane in control and estradiol-treated rats, respectively). Estradiol administration also resulted in a significant decrease in the percentage of perikaryal membrane covered by immunoreactive synapses. These results suggest that physiological levels of estradiol may induce a remodeling of GABAergic inhibitory inputs on arcuate neurons. PMID- 8492912 TI - Serotonin2/1C receptor activation causes a localized expression of the immediate early gene c-fos in rat brain: evidence for involvement of dorsal raphe nucleus projection fibres. AB - Immunocytochemistry has been used to monitor the expression of the immediate early gene c-fos in rat brain following administration of the serotonin2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. At parenteral doses of 2 or 8 mg/kg the drug caused a highly localized expression of the Fos protein in frontal, parietal, cingulate and piriform cortex as well as in claustrum, mamillary bodies, globus pallidus, amygdala, nucleus accumbens and dorsomedial striatum. In particular, the location of heavy Fos immunoreactivity in the primary somatosensory cortex corresponds precisely to that region (layer Va) shown in other reports to receive a dense input of fine, non-varicose fibres which may arise from the dorsal raphe nucleus. All of the Fos-positive brain regions in the present study have been previously demonstrated to contain serotonin2 receptor ligand binding sites. Interestingly, no Fos-positive cells were found in the hippocampus, another brain region known to contain serotonin2 receptors. Pretreatment of animals with the serotonin2/1C receptor antagonist ritanserin (0.4 mg/kg) markedly attenuated Fos expression in all reactive areas of the brain. Counts of reactive cells indicated that this antagonism of the Fos response was statistically significant in these brain regions. Spiperone (1 mg/kg), a mixed serotonin2 and dopamine D2 antagonist, also attenuated the Fos response in the same regions, but had the effect of inducing Fos expression on its own in other extrapyramidal brain regions. Double labelling of reactive cells with different antisera recognizing Fos and neuron-specific enolase, and lack of double labelling with a glial fibrillary acidic protein antiserum, indicated that the Fos expression was in neurons within the brain nuclei examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492913 TI - 5-hydroxytryptamine1 recognition sites in rat brain: heterogeneity of non-5 hydroxytryptamine1A/1C binding sites revealed by quantitative receptor autoradiography. AB - Quantitative in vitro receptor autoradiography was used to characterize the [3H]5 hydroxytryptamine binding sites which are not sensitive to 8-hydroxy-2-(di-N propylamino)tetralin, mesulergine and serotonin-5-O-carboxy-methyl-glycyl tyrosinamide, in a non-5-hydroxytryptamine1A/1B/1C/1D receptor population, in rat brain. Displacement of [3H]5-hydroxytryptamine [in the presence of 100 nM 8 hydroxy-2-(di-N-propyl-amino)tetralin and mesulergine, to block 5 hydroxytryptamine1A and 5-hydroxytryptamine1C sites] with (-)pindolol, 5-hydroxy 3(4-1,2,5,6-tetrahydropyridyl)-4-azaindole, sumatriptan and serotonin-5-O-carboxy methyl-glycyl-tyrosinamide yielded complex competition curves suggesting the presence of 5-hydroxytryptamine1B and 5-hydroxytryptamine1D sites and an additional [3H]5-hydroxytryptamine-sensitive component in rat brain. The non-5 hydroxytryptamine1A/1B/1C/1D binding sites were localized in olfactory tubercle, several nuclei of the amygdala, bed nucleus of the stria terminalis, caudate putamen, CA3 field of the hippocampus, the frontoparietal cortex (motor area) and parts of the striate cortex. All the drugs used had low affinity for the unknown recognition site, which therefore might be comparable to the [3H]5 hydroxytryptamine binding site reported to display low affinity for sumatriptan and 5-carboxamidotryptamine in the brains of various species, the so-called 5 hydroxytryptamine1E site. A comparison of the density of sites labelled with [125I]serotonin-5-O-carboxy-methyl-glycyl-tyrosinamide (representing 5 hydroxytryptamine1B and 5-hydroxytryptamine1D sites) and [3H]5-hydroxytryptamine (under the conditions mentioned above) showed the density of [3H]5 hydroxytryptamine recognition sites to be higher in some structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492914 TI - Evidence that neuropeptide Y is present in GABAergic neurons in the superficial dorsal horn of the rat spinal cord. AB - In order to determine whether or not neuropeptide Y coexists with GABA or glycine in rat dorsal horn, we have examined 84 neuropeptide Y-immunoreactive neurons in laminae I-III with a combined pre- and postembedding immunocytochemical method. All of the neuropeptide Y-immuno-reactive neurons were also GABA-immunoreactive, but they were either non-immunoreactive or weakly immunoreactive with the glycine antiserum. In addition, a double-label immunofluorescence method was used to search for co-localization of neuropeptide Y and [Met]enkephalin in spinal cord. Although the two types of peptide immunoreactivity often coexisted in varicosities around the central canal and in the ventral horn, such coexistence was not seen in the superficial dorsal horn. These results suggest that neuropeptide Y is present in GABAergic neurons in laminae I-III of rat dorsal horn, but that it is largely or completely restricted to those neurons which do not contain glycine. In addition, the cells that contain GABA and neuropeptide Y appear to form a different population from those that contain GABA and [Met]enkephalin. Neuropeptide Y administered by intrathecal injection causes analgesia, and there is evidence that this may involve a presynaptic mechanism. The results of the present study suggest that neuropeptide Y may act in conjunction with GABA to produce presynaptic inhibition of nociceptive primary afferents. PMID- 8492915 TI - Comparison of the intracellular effects of clostridial neurotoxins on exocytosis from streptolysin O-permeabilized rat pheochromocytoma (PC 12) and bovine adrenal chromaffin cells. AB - The inhibitory effects of tetanus toxin, botulinum toxin A, their constituent light chains, and botulinum toxin B were compared using streptolysin O permeabilized rat pheochromocytoma (PC 12) and bovine adrenal chromaffin cells in primary culture. In both types of chromaffin cells exocytosis can be triggered by micromolar amounts of free Ca2+, bovine adrenal chromaffin cells in addition require ATP. In PC 12 cells the isolated tetanus toxin light chain alone blocks exocytosis without any additive. The time-course of the inhibitory action of tetanus toxin light chain in permeabilized PC 12 cells in the absence of ATP is similar to the one obtained with permeabilized bovine adrenal chromaffin cells, in the presence of ATP. Thus, ATP does not seem to be crucial for tetanus toxin (two-chain form) poisoning. Botulinum toxin B (two-chain form), if preactivated by dithiothreitol, also inhibits exocytosis from permeabilized PC 12 cells up to 90% in the absence of ATP. By contrast, botulinum toxin A (two-chain form) or its isolated light chain, which are highly potent in permeabilized bovine adrenal chromaffin cells, causes only a weak inhibition in PC 12 cells. In streptolysin O permeabilized bovine adrenal chromaffin cells omission of ATP during the incubation with the toxin increases the potency of botulinum toxin A light chain. Under the same conditions the effect of tetanus toxin light chain remains unchanged. Tetanus toxin and botulinum toxin B (two-chain forms) probably block a step which occurs during exocytosis from both PC 12 cells and adrenal chromaffin cells and which could be closely related to the final fusion event.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8492916 TI - Bi-stable dendrite in constant electric field: a model analysis. AB - Some neurons possess dendritic persistent inward current, which is activated during depolarization. Dendrites can be stably depolarized, i.e. they are bi stable if the net current is inward. A proper method to show the existence of dendritic bi-stability is putting the neuron into the electric field to induce transmembrane potential changes along the dendrites. Here we present analytical and computer simulation of the bi-stable dendrite in the d.c. field. A prominent jump to a depolarization plateau can be seen in the soma upon initial hyperpolarization of its membrane. If a considerable portion of dendrites are parallel to the field it is impossible to switch off the depolarization plateau by changing the direction and the strength of the electric field. There is nothing similar in neurons with ohmic dendrites. The results of the simulation conform to the experimental observations in turtle motoneurons [Hounsgaard J. and Kiehn O. (1993) J. Physiol., Lond. (in press)]; comparison of the theoretical and the experimental results makes semi-quantitative estimation of some electrical parameters of dendrites possible. We propose modifications of the experiment which enable one to measure dendritic length constants and other parameters of stained neurons. PMID- 8492917 TI - Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy. AB - Macrophages are frequently present within the periaxonal and intramyelinic vacuoles that are located primarily in the posterior and lateral funiculi of the thoracic spinal cord in HIV-associated vacuolar myelopathy. But the role of these macrophages in the formation of the vacuoles is unclear. One hypothesis is that cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha, are produced locally by macrophages and have toxic effects on myelin or oligodendrocytes. The resulting myelin damage eventually culminates in the removal of myelin by macrophages and vacuole formation. We studied thoracic spinal cord specimens taken at autopsy from HIV-positive (+) and HIV-negative individuals. The predominant mononuclear cells present in HIV+ spinal cords are macrophages. They are located primarily in the posterior and lateral funiculi regardless of the presence or absence of vacuolar myelopathy. Macrophages and microglia are more frequent in HIV+ than HIV-negative individuals and these cells frequently stain for class I and class II antigens, IL-1, and TNF-alpha. Activated macrophages positive for IL-1 and TNF-alpha are great increased in the posterior and lateral funiculi of HIV+ individuals with and without vacuolar myelopathy, suggesting they are present prior to the development of vacuoles. Cytokines, such as TNF-alpha, may be toxic for myelin or oligodendrocytes, leading to myelin damage and removal by macrophages and vacuole formation. PMID- 8492918 TI - Allelic heterogeneity in hereditary motor and sensory neuropathy type Ia (Charcot Marie-Tooth disease type 1a). AB - The most frequently found mutation in autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) is a large duplication on chromosome 17p11.2 containing probes VAW409R3, VAW412R3, and EW401. We investigated a family with severe features of HMSN I, and demonstrated the absence of this duplication by a quantitative analysis of the hybridization signals of VAW409R3 and VAW412R3. Linkage analysis, however, revealed linkage with probe VAW409R3a (lod score, 3.22), which demonstrates the existence of allelic heterogeneity within the HMSN Ia locus. These findings have implications for clinical practice and for investigating the identity of the HMSN Ia gene. PMID- 8492919 TI - Adult-onset diabetes mellitus and neurosensory hearing loss in maternal relatives of MELAS patients in a family with the tRNA(Leu(UUR)) mutation. AB - We describe a family with three cases of "clinically incomplete mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome" in which heteroplasmic tRNA(Leu(UUR)) mutation at nucleotide 3243 of the mitochondrial DNA was present in three generations. The amount of mutant genome varied among tissues: it was 60% in the kidney, 72% in the cardiac muscle, and 91% in the liver of the female proband's affected brother and 63% in the kidney, 71% in the cardiac muscle, and 71% in the liver of the female proband's perinatally deceased son. The tRNA(Leu(UUR)) mutation was also carried by the siblings of the proband's affected mother. None of them had any clinical signs of MELAS syndrome. This syndrome has the new feature of being associated with adult onset diabetes mellitus, neurosensory hearing loss, and short stature. PMID- 8492920 TI - Interphysician agreement in the diagnosis of subtypes of acute ischemic stroke: implications for clinical trials. The TOAST Investigators. AB - To test interphysician agreement on the diagnosis of subtype of ischemic stroke, we sent subtype definitions and 18 case summaries (clinical features and pertinent laboratory data) to 24 neurologists who have a special interest in stroke, and asked them to determine the most likely subtype diagnosis. The overall agreement was 0.64 (Kappa [K] = 0.54). Interphysician agreement was highest for the diagnoses of stroke secondary to cardioembolism (K = 0.75) or to large-artery atherosclerosis (K = 0.69). Individual physicians varied widely; four agreed with the consensus diagnosis in all 18 cases, while six others disagreed with the consensus diagnosis in three to five cases. Our level of interphysician agreement is greater than that reported in other studies and was substantial. However, despite using subtype definitions and being given extensive information often not available in the acute setting, physicians still disagree about the etiology of stroke, particularly in regard to stroke due to small artery occlusion or of undetermined etiology. Physicians seem reluctant not to attribute stroke to a specific etiology. The uncertainty about subtype diagnosis will affect interpretation of the results of clinical trials in patients selected by the subtype of ischemic stroke and also suggests that results of treatment as affected by subtype should be cautiously interpreted unless efforts to assure uniformity are included in the trial's operations. Refinement of algorithms for determining subtype of ischemic stroke do improve interphysician agreement. Such criteria should be applied strictly, and trials should include measures to assure the most uniform diagnosis of stroke subtype possible. PMID- 8492921 TI - Human immune globulin infusion in Guillain-Barre syndrome: worsening during and after treatment. AB - Because of an unexpectedly high rate of worsening, we report the results of treatment of Guillain-Barre syndrome with a standard regimen of human immune globulin (HIG) in 15 consecutive patients. Patients were treated with 1.5 g/kg HIG for 4 days beginning a mean of 7 days after the first symptoms. Eight stabilized or improved, but seven deteriorated during or within the first 5 days after treatment, and four remained ventilator-dependent for at least 2.5 months. One had a severe relapse 5 weeks after treatment. Five patients subsequently received plasma exchange and two improved. Our experience varies from previous reports that have endorsed HIG treatment for Guillain-Barre syndrome. PMID- 8492922 TI - Oral levodopa/carbidopa solution versus tablets in Parkinson's patients with severe fluctuations: a pilot study. AB - Four patients with Parkinson's disease, optimally treated with levodopa/carbidopa (LD/CD) tablets but experiencing severe motor fluctuations, underwent an open trial of a levodopa/carbidopa/ascorbic acid solution (LCAS) orally at timed intervals. LCAS reduced bradykinesia, decreased dysfunctional dyskinesia, and increased functional "on" time when compared with previous LD/CD tablet therapy. Oral LCAS allowed better titration of levodopa dosage and offered a more predictable response than LD/CD tablets. Preparation and oral consumption of LCAS was easy and inexpensive. LCAS may be a practical alternative for patients whose motor fluctuations fail to respond to optimal therapy with LD/CD tablets. PMID- 8492923 TI - Blood levodopa levels and unified Parkinson's disease rating scale function: with and without exercise. AB - We studied 10 regular exercising men with Parkinson's disease on levodopa (LD) under two conditions--no exercise and vigorous exercise started 1 hour after LD ingestion. We compared LD levels and motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS). There was a high degree of agreement between plasma LD level and the patients' UPDRS scores 30 minutes later (mean Eta2 = 0.84) in both conditions, with no difference between the two. We conclude that LD levels accurately reflect UPDRS motor function in these patients, and that vigorous exercise started 1 hour after LD ingestion does not influence LD or motor scores. PMID- 8492924 TI - New-onset seizures in critically ill patients. AB - We studied causes of new-onset seizures in 55 patients admitted to medical and surgical intensive care units between 1981 and 1991. In one-third of the patients, sudden withdrawal of narcotic agents was associated with tonic-clonic seizures. In another third, acute metabolic changes, predominantly severe hyponatremia (sodium < or = 125 mEq/l), accounted for new-onset seizures. In eight patients, drug toxicity (antibiotics and antiarrhythmic agents) predisposed to seizures. Only five patients had previously unrecognized structural CNS abnormalities that were manifested by focal or generalized tonic-clonic seizures. In six patients, the cause remained unknown. Twenty-four patients had recurrent seizures despite treatment with standard antiepileptic drugs. Status epilepticus occurred in four patients. Outcome was poor in only 34% of the patients, particularly in those with metabolic causes. Sudden withdrawal of narcotic drugs may be a significant cause of new-onset seizures in patients with life threatening disorders. PMID- 8492925 TI - Double-blind controlled study of methazolamide in the treatment of essential tremor. AB - We studied the effect of the carbonic anhydrase inhibitor methazolamide in 25 patients with essential tremor (ET) in a double-blind, placebo-controlled trial. Tremor assessment included patient self-reporting of functional disability, clinical rating of motor tasks and tremor severity, and accelerometric measurements. There was no significant difference between methazolamide and placebo in any of the assessments. Side effects, paresthesias, sedation, headaches, and gastrointestinal symptoms were common. Only two patients elected to remain on the drug after the study. Methazolamide has only limited efficacy in the treatment of essential tremor. PMID- 8492926 TI - Neuroprotective effects of memantine. PMID- 8492927 TI - Nondystonic torticollis. PMID- 8492928 TI - Left hemiparalexia. PMID- 8492929 TI - Numb chin syndrome. PMID- 8492930 TI - Alzheimer pathology. PMID- 8492931 TI - Spinal cord sarcoidosis. PMID- 8492932 TI - Low CSF pressure. PMID- 8492933 TI - Glucagon and ALS. PMID- 8492934 TI - A causal role for amyloid in Alzheimer's disease: the end of the beginning. PMID- 8492935 TI - IVIg for GBS: potential problems in the alphabet soup. PMID- 8492936 TI - Clinical neurology as data for basic neuroscience: Tourette's syndrome and the human motor system. PMID- 8492937 TI - Disconnection syndromes: an overview of Geschwind's contributions. PMID- 8492938 TI - The photic sneeze reflex: literature review and discussion. PMID- 8492939 TI - Relapse in Guillain-Barre syndrome after treatment with human immune globulin. AB - Seven adult patients received human immune globulin intravenously as initial therapy for Guillain-Barre syndrome. Although all patients initially stabilized or improved, five patients deteriorated 1 to 16 days after completion of treatment. In all five patients, clinical worsening included loss of at least one functional grade together with a decreased forced vital capacity. We subsequently treated each patient with a course of plasma exchange, which led to varying degrees of clinical improvement in four. In contrast to previously reported relapse rates for Guillain-Barre syndrome, our experience suggests that clinically significant relapses may occur in patients more often following human immune globulin therapy than after either plasma exchange or no therapy. PMID- 8492940 TI - Treatment of inclusion-body myositis with high-dose intravenous immunoglobulin. AB - We report the treatment of four patients with inclusion-body myositis (IBM) and severe slowly progressive weakness using high-dose intravenous immunoglobulin (IVIg). After two monthly infusions, the strength of the proximal and less atrophic muscle groups improved or normalized in three of the four patients. The improvement lasted from 2 to 4 months. Intravenous immunoglobulin is the first treatment modality to improve the strength of some muscles in patients with this disabling inflammatory myopathy. In view of the high cost of IVIg, the unexpected but encouraging results from this pilot study warrant a controlled trial. PMID- 8492941 TI - Nonvasculitic, steroid-responsive mononeuritis multiplex. AB - We report two patients with mononeuritis multiplex, both of whom had focal inflammation of the perineurium and endoneurium on sural nerve biopsy without necrosis of blood vessel walls, histologic evidence of lymphoid malignancy, or mycobacterial infection. The predominant early sensory symptoms were asymmetric pain and paresthesias; subsequently, muscle weakness developed. Electrophysiologic studies showed an asymmetric sensorimotor axon loss radiculoneuropathy with denervation of limb and paraspinal muscles. Spinal fluid protein was elevated in one patient. There was no cause or underlying systemic disease. Marked improvement occurred with steroid therapy. PMID- 8492942 TI - Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. AB - We followed 16 patients with a variety of mitochondrial diseases over one to four periods of treatment (2 months each) with coenzyme Q10 plus vitamins K3 and C, riboflavin, thiamine, and niacin, using independent measures of oxidative metabolism to assess efficacy. There were large (> threefold) increases in serum coenzyme Q10 concentrations with treatment, but no measure of oxidative metabolism showed significant improvement with treatment for the group, nor did any individual patient show significant, reproducible, objective clinical improvement. The results suggest that coenzyme Q10 plus vitamin therapy does not significantly improve mitochondrial oxidative metabolism in patients with mitochondrial disease in general. Any clinical benefit that may follow from short term administration appears slight. PMID- 8492943 TI - Severe disturbances in speech, swallowing, and gait following stereotactic infrathalamic lesions in Gilles de la Tourette's syndrome. AB - A 40-year-old man with severe Gilles de la Tourette's syndrome characterized by forceful self-injurious motor tics, coprolalia, and obsessive-compulsive disorder had bilateral anterior cingulotomies and bilateral infrathalamic lesions placed stereotactically during two neurosurgical procedures. During the second procedure, the patient acutely developed a marked dysarthria. Postoperatively, he manifested a severe gait disturbance with postural instability, bradykinesia, axial rigidity, micrographia, and a profound swallowing disorder. MRI showed asymmetric (left > right) low-density areas in an infrathalamic region as well as low-density areas bilaterally in the anterior cingulate gyri. Although the patient's tic and obsessive-compulsive symptoms improved, the self-injurious motor tics along with other motor and phonic tics have recurred. The patient's speech remains largely unintelligible 8 months following the last surgical procedure, and the other neurologic deficits remain unchanged. PMID- 8492944 TI - Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. AB - Pentobarbital coma (PBC) is a treatment for patients with refractory status epilepticus, but there are currently few guidelines for choosing when to initiate or continue this therapy. To identify potential prognostic factors in this setting, we reviewed the course of 17 adult patients treated with a standardized protocol of PBC for refractory status epilepticus over the past 6 years. PBC was extremely effective in aborting seizures in 16 of 17 patients, but 11 of the patients developed severe hypotension that required therapy with vasopressors. Six of the patients had full recoveries or developed only minimal residual deficits following PBC, two developed severe neurologic deficits, and nine died. Survival was associated with a history of epilepsy, absence of multiorgan failure before or during PBC, age < 40 years, and absence of hypotension requiring vasopressors during PBC. Long-term follow-up in seven of eight survivors (mean, 2.9 years; range, 1 to 5 years) showed that patients' conditions remained stable after discharge from the hospital. Thus, although PBC is effective in controlling ongoing seizures, the therapy frequently leads to significant hypotension. This side effect may be especially troublesome in patients with the negative prognostic indicators identified in this study. These findings highlight the need for alternative approaches in the management of these patients. PMID- 8492945 TI - Cardiovascular and hormonal responses to liquid food challenge in idiopathic Parkinson's disease, multiple system atrophy, and pure autonomic failure. AB - We investigated the effect of a balanced liquid meal on blood pressure (BP) and heart rate (with patients supine and during head-up tilt), and on levels of plasma catecholamines, glucose, and insulin, in patients with idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), pure autonomic failure (PAF), and in healthy subjects (controls). After food, supine BP fell in IPD, but to a greater extent in MSA and PAF. In controls, BP was unchanged. Head-up tilt did not lower BP in IPD and controls, but there was a postprandial fall to lower levels in both MSA and PAF. Plasma norepinephrine levels rose in IPD pre- and postprandially during tilt, but were unchanged in MSA and PAF. These data suggest that in IPD, food causes a smaller fall in supine BP than in MSA and PAF. In IPD, as in controls, food does not induce or unmask postural hypotension, unlike in MSA and PAF, in which BP falls to even lower levels. There are therefore differences in the responses to food ingestion between these groups. This may be of value in separation of these disorders at an early stage. PMID- 8492946 TI - MRI changes in intracranial hypotension. AB - We report seven patients with the syndrome of intracranial hypotension who were referred to Memorial Sloan-Kettering, primarily because of suspicion of meningeal tumor or infection raised by the finding of meningeal enhancement on MRI. In three patients, symptoms occurred after lumbar puncture; in four, there was no clear precipitating event. Lumbar puncture after MRI in six patients revealed low CSF pressure (six patients) and pleocytosis or high protein, or both (four patients). Three patients had subdural effusions. Six patients had measurable descent of the brain on midsagittal images. Postural headache resolved in all seven patients, six of whom had follow-up MRIs. Meningeal enhancement resolved or diminished in all six. Subdural effusions resolved spontaneously in two and were evacuated (but were not under pressure) in one. Downward brain displacement improved or resolved in all patients. The clinical syndrome and MRI abnormalities generally resolve on their own. An extensive workup is not helpful and may be misleading. Patients should be treated symptomatically. PMID- 8492947 TI - Amyotrophic lateral sclerosis mortality in Italy, 1958 to 1987: a cross-sectional and cohort study. AB - We analyzed the mortality rates of amyotrophic lateral sclerosis (ALS) in Italy from 1958 to 1987. The overall mean annual mortality rate, adjusted to the 1981 Italian population, was 0.68/100,000 (95% confidence interval, 0.64 to 0.72); 0.86 for men; and 0.62 for women. During that period, mortality increased for both sexes: from 1958/1962 to 1983/1987, mortality increased by 60% for women and 24% for men. The slope for women was 0.07, and for men, 0.02. Moreover, the mortality rate increased in older age groups and was stable for subjects under 45 years old. There was no clear birth-cohort effect, but in any cohort the age specific mortality rate increased with advancing age, with no decline for the oldest age. Based on these data, the increase of ALS mortality rates is probably due to the effect of changing methodologic and demographic variables and the decrease of mortality of some competing diseases, rather than a real rise of the risk in the whole population or in specific birth cohorts. PMID- 8492948 TI - Neurocognitive dysfunction in the eosinophilia-myalgia syndrome. AB - The eosinophilia-myalgia syndrome (EMS), a multisystem disorder associated with ingestion of L-tryptophan-containing products, causes sclerodermatous skin changes, cardiopulmonary disease, and a range of peripheral neurologic complications. Many EMS patients also report cognitive difficulty in association with the disease. To determine the frequency of objective neurocognitive impairment in EMS patients with subjective complaints of cognitive difficulty and to assess the relationship of neurocognitive loss with demographic features, degree of peripheral eosinophilia, and psychiatric diagnosis, we compared 24 EMS patients with 32 age- and education-matched healthy controls, using a comprehensive neuropsychological test battery. EMS patients additionally underwent a psychiatric interview and rheumatologic evaluation. Sixty-two percent (15 of 24) of the EMS patients demonstrated neurocognitive deficits. Compared with healthy controls, EMS patients demonstrated significant impairment on tests of verbal memory, visual memory, conceptual reasoning, and motor speed. Cognitively impaired EMS patients did not differ from those without cognitive impairment on demographic markers, degree of peripheral eosinophilia, presence of peripheral neuropathy, or frequency of concurrent psychiatric disorder, including major depression. These data support the hypothesis that EMS is associated with an encephalopathy in addition to its previously recognized peripheral neuropathy and other rheumatologic manifestations. PMID- 8492949 TI - Tardive stereotypy and other movement disorders in tardive dyskinesias. AB - We reviewed the medical records and videotapes of 100 patients with tardive dyskinesia (TD) referred to our movement disorders clinic to characterize the spectrum of hyperkinetic movement disorders caused by dopamine receptor blocking drugs (DRBD). Tardive stereotypy, present in 78 patients, was the most common type of TD, followed by tardive dystonia, akathisia, tremor, chorea, and myoclonus. Sixty-four had a combination of these hyperkinesias. In a second study, a "blind" review of videotapes of patients with a variety of movement disorders found that DRBD were the cause of stereotypic movements in 89.3% of patients, and 96.1% of patients with TD had stereotypy. We conclude that stereotypy can be readily differentiated from other hyperkinetic movement disorders and that its presence in an adult is highly suggestive of prior exposure to DRBD. PMID- 8492950 TI - Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. AB - Using a 1.5-tesla GE Signa MR scanner, we imaged the brains of 14 right-handed Tourette's syndrome (TS) patients (11 men, three women), aged 18 to 49 years, who had minimal lifetime neuroleptic exposure. We also studied an equal number of normal controls individually matched for age, sex, and handedness and group matched for socioeconomic status. We circumscribed basal ganglia on sequential axial images from spin-echo proton density-weighted acquisitions (TR 1,700, TE 20; slice thickness, 3 mm with 1.5-mm skip) and submitted the images for three dimensional processing at a computer graphics workstation. Our hypothesis of lenticular nucleus volume reduction in TS was confirmed for the left- but not the right-sided nucleus. Post hoc analyses revealed smaller mean volumes of the caudate, lenticular, and globus pallidus nuclei compared with controls on both the right and left. Further analyses of basal ganglia asymmetry indices suggest that TS basal ganglia do not have the volumetric asymmetry (left greater than right) seen in normal controls. These findings confirm and extend prior phenomenologic, neuropathologic, and neuroradiologic studies that implicate the basal ganglia in the pathogenesis of TS. PMID- 8492951 TI - Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. AB - To define the site of pathology in Tourette's syndrome (TS), we performed a volumetric MRI study of basal ganglia structures and lateral ventricles on 37 children with this disorder and 18 controls. There were no statistically significant differences in the size of the right or left caudate, putamen, globus pallidus, or ventricles in these populations. In contrast, there were significant differences for measures of symmetry in the putamen and the lenticular region. Virtually all controls (17 right- and one left-handed) had a left-sided predominance of the putamen, whereas in 13 of 37 TS subjects, a right predominance exceeded that of any control. Statistical comparisons among TS patients, with (n = 18) or without (n = 19) attention-deficit hyperactivity disorder (ADHD), and controls showed significant differences for the volume of the left globus pallidus and for lenticular asymmetry. Post hoc evaluations showed that in the TS + ADHD group, the volume of the left globus pallidus was significantly smaller than the volume of the right and that lenticular asymmetry was due to a greater right-sided predominance in the TS+ADHD group. This study lends further support to proposals that claim the basal ganglia is involved in the pathogenesis of TS and also suggests that the comorbid problem of ADHD is related to regional changes that differ from those primarily associated with tics. PMID- 8492952 TI - The capsular warning syndrome: pathogenesis and clinical features. AB - Transient ischemic attacks (TIAs) are not homogeneous and may consist of subsets with mechanisms as varied as their stroke counterparts. We describe a form of TIA in 50 patients where crescendo episodes of ischemia were restricted to the region of the internal capsule, usually causing symptoms affecting face, arm, and leg. These patients composed 4.5% of a consecutive series of patients admitted with TIAs over a 15-year period and 33% of all TIAs classified as subcortical. We believe that the ischemia was most often due to hemodynamic phenomena in diseases, single, small penetrating vessels. When cerebral infarction developed, it was usually lacunar and involved a single penetrating vessel, although occasionally striatocapsular or anterior choroidal artery territory infarction occurred. There was no evidence of artery-to-artery or heart-to-artery embolism. Resistance to various forms of therapy, including hemodiluting, anticoagulant, and thrombolytic agents, was common. Because of dramatic and easily recognizable clinical presentation, apparent specific pathophysiologic mechanism, and the development of early capsular stroke in a high proportion of cases (42%), we have termed this the "capsular warning syndrome." PMID- 8492953 TI - Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease. AB - Olfactory dysfunction occurs in most patients with idiopathic Parkinson's disease (PD). In this study, we sought to determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups between (1) the olfactory test scores and (2) measures of motor symptom severity, disease stage, and medication usage. These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that olfactory testing may be useful in their differential diagnosis. PMID- 8492954 TI - Risk factors associated with equine motor neuron disease: a possible model for human MND. AB - Equine motor neuron disease (EMND), a newly described neurodegenerative disease, bears a striking resemblance to progressive muscular atrophy (PMA) in humans. We present a comparison of the equine and human diseases and the results of a case control study conducted to identify intrinsic factors associated with EMND. Cases included all horses with a confirmed diagnosis of EMND diagnosed in the United States since 1985 (32 cases). Controls included horses diagnosed with either cervical stenotic myelopathy, equine degenerative myeloencephalopathy, or protozoan myelitis at the Veterinary Teaching Hospital at the College of Veterinary Medicine, Cornell University (153 controls). Logistic regression analysis identified factors associated with the risk of EMND. Risk factors considered were age, sex, and breed of the horse. Most cases of EMND (30 of 32) have been sporadic. There was a breed association with the risk of EMND. Quarter horses were at a high risk for developing EMND (odds ratio [OR] = 12.7; 95% confidence interval, 3.3 to 49.6); thoroughbred horses were at increased risk (OR = 2.9, 0.8 to 10.4). There was also an age association with the risk of EMND. The risk increased with age, peaked at 16 years, and then declined, a pattern similar to that for amyotrophic lateral sclerosis in humans. There was no sex association with the disease. Despite the breed association, equine lymphocyte antigen studies have not revealed a systematic pattern, suggesting that genetic factors influencing susceptibility to EMND may be outside the major histocompatibility complex. PMID- 8492955 TI - Myopathies associated with human immunodeficiency virus and zidovudine: can their effects be distinguished? AB - Myopathy may occur as a complication of human immunodeficiency virus type 1 (HIV) infection or from its treatment, zidovudine (ZDV). We reviewed our experience with HIV-infected subjects referred for neuromuscular evaluation and compared features of myopathy in ZDV-treated (+ZDV) and untreated (-ZDV) patients. Fifty patients had myopathy, 25 diagnosed by pathologic criteria and 25 by clinical and other laboratory support. Twenty patients with myopathy had weight loss sufficient for the diagnosis of HIV wasting syndrome. Thirty-one subjects were +ZDV and 19 were -ZDV. Patients in each group presented with proximal weakness, although myalgia was more common in +ZDV patients. Both groups had elevated serum CK to a similar degree (medians: +ZDV, 485; -ZDV, 471). Muscle biopsies revealed myofiber degeneration, variable inflammatory infiltrates, inclusion bodies, and mitochondrial abnormalities in both groups. We followed response to ZDV withdrawal in 15 patients. Four had increased strength, three noted less myalgia, and eight had no clinical improvement. Twelve of 13 patients improved with prednisone. Although it is difficult to distinguish the myopathies of HIV and ZDV by clinical or pathologic criteria, in the majority of our patients, myopathy is due to HIV rather than ZDV. PMID- 8492956 TI - Acetylcholine receptor antibodies in juvenile myasthenia gravis. AB - We analyzed relationships among pubertal stage at disease onset, sex, disease severity, and acetylcholine receptor antibody (AChR Ab) levels in 46 patients with autoimmune juvenile myasthenia gravis (JMG). Female predominance was least in children with prepubertal disease onset (F:M = 1.3:1) and increased in patients with peripubertal (F:M = 1.8:1) and postpubertal (F:M = 14:1) onset. Seronegative JMG was most common in children with early disease onset: 4 of 9 (44%) with prepubertal, 4 of 22 (18%) with peripubertal, and 0 of 15 (0%) with postpubertal onset were seronegative. The rapid therapeutic response to plasmapheresis was useful in distinguishing some patients with seronegative JMG from those with congenital myasthenia gravis (CMG). The high frequency of seronegative JMG in patients with prepubertal onset indicates that AChR Ab assays do not adequately discriminate between JMG and CMG in young children. Furthermore, the different sex distribution in patients with different pubertal stages at disease onset suggests that sex hormones play an important modulating role in JMG. PMID- 8492957 TI - The locus ceruleus and dementia in Parkinson's disease. AB - We compared numbers of neuronal profiles in the locus ceruleus (LC) from sections of brainstem in 13 patients with Parkinson's disease (PD) without concurrent Alzheimer's disease (AD) with counts from age-matched controls and from patients with PD and concurrent AD. We also evaluated the relationships between presence of dementia or LC neuronal loss and additional pathologic measures related to dementia in PD. Among patients with PD without concurrent AD, the presence of dementia was associated with significantly lower LC neuronal counts (at all anatomic levels); greater neuronal loss within the ventral tegmental area, nucleus basalis of Meynert, and possibly the medial (but not the lateral) substantia nigra pars compacta; and more Lewy bodies in the anterior cingulate gyrus. Correlations between lower LC neuronal counts and these other pathologic measures were generally positive and often significant. We conclude that dementia in PD is associated with pathologic involvement of multiple extranigral neuronal populations. PMID- 8492958 TI - Dextromethorphan and its combination with phenytoin facilitate kindling. AB - We implanted 20 rats with bipolar electrodes and randomly distributed them into four groups that received intraperitoneal injections of phenytoin (PHT) (20 mg/kg), dextromethorphan (DM) (50 mg/kg), PHT+DM (20 and 50 mg/kg, respectively), or saline (C), 15 minutes before each daily stimulation. The number of stimulations needed to reach stage 3 seizures was 14.4 +/- 1.7 (C); 28 +/- 12 (PHT, p < 0.001); 6.2 +/- 3.9 (DM, p < 0.05); and 7.6 +/- 3.4 (PHT+DM, p < 0.05), suggesting that DM accelerated the expression of kindled seizures. Daily injections of DM and of DM+PHT without stimulation resulted in progressive seizure buildup to stage 3 in 4.8 +/- 6.2 (DM) or in 8 +/- 4.8 (DM+PHT) trials. We demonstrated savings in six kindled animals reinjected after 1 month. These results and previous experimental and clinical data suggest that DM may be epileptogenic when given repeatedly in high doses. PMID- 8492959 TI - Color perception profiles in central achromatopsia. AB - Central achromatopsia is an impairment of color perception caused by damage to the visual association cortex. Its psychophysical underpinnings remain poorly defined. We report our attempt to characterize the defect along critical dimensions of color space, taking advantage of the same standardized tasks that allow detailed profiles in patients with retinal cone defects. We studied two patients. The results in patient 1 showed that perceptual color space was collapsed along the red-green (R-G) and short-wavelength-sensitive cone (S-cone) dimensions but that discriminations along achromatic dimensions were relatively preserved. Additional observations showed that the defect was dependent on target size, and that processing of surface and light source effects that differ from color (eg, transparency) was intact. Patient 2 showed a less severe color processing defect involving signals arising from the S-cones of the retina, although an R-G defect was also present. The profiles in these two patients demonstrate that central achromatopsia encompasses a range of color processing impairments with varied psychophysical characteristics. PMID- 8492960 TI - [The use of erythropoietin in HIV myelodysplasias. Preliminary study]. AB - The authors gave recombinant human erythropoietin to four anaemic patients with HIV-infection treated with zidovudine. After erythropoietin administration an increase in haemoglobin, erythrocytes and haematocrit was observed and patients could continue AZT therapy. PMID- 8492961 TI - [Determination++ of CA 15-3 in the control of primary and metastatic breast carcinoma]. AB - From April 1987 to December 1990 490 women and 5 men suffering from primary or metastatic breast cancer underwent 1485 assays of the CA 15-3 marker using a radioimmunometric method supplied by Centocor based on two monoclonal antibodies: 115D8 and DF3. The dose-response curve constructed using 5 standards. Clinical and instrumental monitoring of patients continued for at least one year after the last assay. In line with the bibliographical data and the Author's extensive experience a cut-off 40 U/ml was selected. On this basis the percentages of sensitivity (58.2), specificity (96.0), accuracy (85.0), and positive (85.7) and negative (84.9) predictive value were calculated and were in overall terms better than those obtained using a threshold of 30 U/ml. A chart marking the trend of percentages for assays in patient with active metastasis showed that there was a rapid increase over 40 U/ml, reaching 100% over 90 U/ml. In asymptomatic patients, who were considered "ned" following clinical and instrumental controls, it was rare to find and assay level over 50 U/ml (13/1050). The authors underline the importance of serial controls in post-treatment follow-up at intervals of not less than one month and not more than 3 months for 1-2 years, and subsequently every six months. This marker has been found to offer considerable prognostic, but not diagnostic, reliability during the preoperative period and even more so during cancer control due to the possible early detection of metastasis in the viscera or skeleton, especially if this is conspicuous. On the other hand, the marker shows limited sensitivity to cutaneous or regional lymph node metastasis. In this pathology levels in excess of 200 U/ml have never been observed. CA 15-3 is particularly important in evaluating the efficacy of anti-tumour therapies or deciding whether they are worth continuing. In conclusion, a few general comments are made regarding the indications for doses and the value of the marker in controlling patients treated for breast cancer. PMID- 8492962 TI - [Dyslipidemia in obesity: pathogenetic considerations and our experience]. AB - The prevalence of obesity is increasing today in western industrialized countries: therefore, many authors are focusing their attention on its multiple endocrine and metabolic effects. Because of the pathogenetic linkage between obesity and dyslipidemia, we have studied serum lipid pattern in a group of obese women: HDL-Cholesterol (HDL-C) deficiency was the most striking lipoproteinemic disorder. This fact points out, in our opinion, that obesity must be considered as a risk factor for cardiovascular disease. PMID- 8492963 TI - [Glyco-lipid changes in hypertensive diabetic patients undergoing treatment with nifedipine and captopril]. AB - Atherosclerosis in diabetic subjects is improved by the reduced repair capacity of endothelial damage and by the increased platelet aggregation, peculiar to diabetic pathology. The contemporary presence of high blood pressure, diabetes and lipoidoproteinosis, increasing the possibility of cardiovascular damage, also under well-controlled blood pressure values, certainly increases the risk of atherosclerosis. However we have valued the presence of lipoidoproteinosis in 52 of our diabetic-hypertensive patients in a follow-up of 40 months. The patients have been split in to two groups of 26 patients each, one being treated with nifedipine, the other to with captopril. The data obtained have been compared with the data for the two control groups (non diabetic patients). The selection has been carried out according to established criteria. We have investigated: glycaemia, total cholesterol, HDL-C, LDL-C, triglycerides, tot. Chol./HDL-C, LDL C/HDL-C. During follow-up the blood pressure values were significantly reduced (p < 0.01) (captopril: delta SBP = -13.88, delta DBP = -12.38, nifedipine: delta SBP = -22.03, delta DBP = -21.35). In the nifedipine group lipoidoproteinosis has been more marked: delta% glicaemia = +17.69, delta% cholesterolemia = +20.11; delta% CFR = +18.57; LDL-C = +35.11; delta% VRF = +34.61, while in the patients treated with captopril we have had the following results: delta% glycaemia = +15.43; delta% cholesterolemia = +16.36; delta% LDL-C = +26.68. The control group with nifedipine treatment have shown only increased values of cholesterolemia: delta% = +4.80, moreover in the control group treated with captopril we have observed a reduction of VRF: delta% = -15. A significant relationship between total cholesterolemia and glycaemia in the group with nifedipine treatment (p < 0.01) and captopril (p < 0.01) has been reported. This study could appear to underline the autonomic nervous system activation by nifedipine which does not affect lipoidoproteinosis in diabetic hypertensive subjects. This would seem to confirm on the contrary, the utility of captopril in the treatment of atherosclerotic subjects, as diabetic hypertensive patients. PMID- 8492964 TI - [Efficacy of and tolerance to a new NSAID in the treatment of arthrosis: droxicam. Randomized study versus tenoxicam]. AB - A four-week open study was carried out to evaluate the efficacy and tolerability of droxicam, a new NSAID, in the treatment of painful osteoarthritis (OA). The results were compared with those obtained treating a similar group of patients with tenoxicam, at the same dosage of 20 mg/day, orally administered. The study showed that both drugs are effective in treating OA, with a mild predominance of droxicam in decreasing pain, functional limitation and chronic inability score. Tolerability was excellent or good in over 70% of patients and only one subject of each group was dropped out for severe side-effects. According to the Authors droxicam has shown to be an effective analgesic and anti-inflammatory agent as judged by its efficacy on pain relief and joint mobility in OA. PMID- 8492965 TI - [Effect of high and low doses of methotrexate (MTX) on bone mass in subjects treated for osteosarcoma of the limbs]. AB - Twenty-three patients with highly malignant localized osteosarcoma receiving neoadjuvant chemotherapy with MTX randomly administered at high (7500 mg/m2) and low (750 mg/m2) doses underwent serial densitometric controls at the start of treatment and after 18 and 36 months. Increasing BMC levels at both examination points were observed in all subjects examined over time, but, contrary to findings in the control group, this increase was not statistically significant using the paired T test. Significantly lower BMC levels in relation to the control group were only found in the group treated with high doses of MTX at MDP but not PM. Reduced density at MDP alone, a site in which trabecular bone is prevalent, shows that MTX predominantly acts at the level of the latter in line with its greater sensitivity to the action of osteopenic agents. PMID- 8492966 TI - [Cardiac block caused by metastasis of lung adenocarcinoma to the bundle of His]. AB - It is well known from autopsy series that metastatic tumors of the heart can be found in 1.5% to 21% of patients with malignancies and the incidence of cardiac metastases is showing a gradual increase in recent years. The most common cause of metastatic heart disease is bronchial carcinoma followed by carcinoma of the breast, pleural mesothelioma, malignant melanoma, leukemia and lymphoma, in decreasing order of frequency. However metastatic cancer to the heart is not commonly diagnosed prior to death. Atrial extension has been reported as a common route of local spread in patients with bronchial carcinoma, but cardiac conduction system invasion is infrequent. The purpose of this report is to describe an unusual case of pulmonary adenocarcinoma that presented with cardiac manifestations mimicking atrioventricular (AV) block. This AV block was corrected by pacemaker. Chest radiography and bidimensional echocardiography didn't visualize important lesions. The cardiac findings at autopsy were remarkable not only for the severity of epicardial, myocardial and endocardial involvement, but for the metastatic implants into the His bundle and for the elective and wide infiltration of bifurcating His bundle. On addition histological examination revealed neoplastic emboli in the myocardial lymphatics. No valvular involvement was noted. Technical annotation: histological examination of the conduction system of the heart has been carried out on serial sections with the technique devised by one of the present authors. Bichromic (hematoxylin-eosin) and trichromic (Heidenhain-azan) stainings have been routinely employed. PMID- 8492967 TI - [Gaucher's disease: study of a family from Friuli]. AB - Gaucher's disease is the most frequent of lysosomal storage diseases. In a family study two affected sisters of a type I patient were identified. Two of them underwent splenectomy, so reaching hematological normalization. PMID- 8492968 TI - [Examples of thyroid pathology in art]. AB - The article gives some examples in pictorial art of thyroid pathologies, ranging from simple to nodular goitre, including cretinism and exophthalmos. A brief reflection on the physiopathology of goitre is presented. PMID- 8492969 TI - [Update on Gaucher's disease]. AB - Gaucher's disease is a lipidosis caused by deficiency of the enzyme glucocerebrosidase (glucosylceramidase) with secondary accumulation of glucocerebrosides in macrophage lysosomes. Three clinical forms of the disease have been described with autosomal recessive genetic basis. They are caused by many different mutations in glucocerebrosidase gene which have been recently identified. The infantile (type III) and juvenile (type II) forms involve the central nervous system and are very rare. Type I is a non neuronopathic form and is the most common lysosomal storage disease, reaching an incidence of 1 in 2500 births among Ashkenazi jews. Clinical manifestations include splenomegaly and hypersplenism, while bone and lung involvement are less common. Most patients have a mild course and a normal life expectancy, but some others suffer for heavy bone pain that greatly inhabilitate them. A distinctive storage cell is present in bone marrow, but diagnostic confirmation is based upon leucocytes or fibroblasts enzyme assay. Total or partial splenectomy is the treatment of choice for correcting hematological abnormalities. Allogeneic bone marrow transplantation was successfully employed in some cases, while studies on retroviral-mediated gene transfer are undergoing. Promising clinical results were obtained in last two years by chronic infusion of purified macrophage-targeted glucocerebrosidase enzyme. New experience is required in selecting patients for this expensive regimen and establishing duration of therapy. PMID- 8492970 TI - [Solid tumors associated with HIV infection]. AB - Between December 1986 and December 1991, the Italian Cooperative Group on AIDS related tumours documented 94 HIV related solid tumours. Of 21 germinal testicular tumours collected, ten were seminomas. Cervical carcinoma was observed observed in 28 IVDAs (intraepithelial in 8 and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in 14 patients. Also reported were two cases of colorectal carcinoma, one anorectal carcinoma, one pancreatic carcinoma, one carcinoid, one oral carcinoma. Of the central nervous system tumours, were diagnosed 3 cases of glioblastomas, one medulloblastoma and one meningioma. This retrospective study shows that while oral and anorectal tumours were very rarely observed, a wide spectrum of other HIV-related solid tumours were found in this series. The required therapeutic approaches may not necessarily be influenced by the HIV infection, in contrast with the observed pattern for treatment of EKS and lymphomas in HIV infected subjects. PMID- 8492971 TI - [Acute pneumonia and cell-mediated immunity in patients with HIV infection]. AB - The aim of this retrospective study is to evaluate the correlation between T-cell immunity and pulmonary disorders in a group of Italian subjects with HIV infection. HIV-infected patients seen at the Institute of Infectious Diseases, University of Verona, were included in this study if they had a specific acute pneumonia, a CD4+ cell count and a CD4+/CD8+ ratio during the 60 days immediately before the onset of pulmonary disease. Cases receiving any antimicrobial prophylaxis were excluded. Pneumonia was recognized by usual clinical and radiologic abnormalities. The diagnostic procedure included sputum examination, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. The specimens were processed for bacterial, mycobacterial and fungal stains and cultures. Ziehl Neelsen, periodic acid-Schiff and silver methenamine stains were performed on the transbronchial biopsy specimens in addition to usual pathologic examinations mononuclear. Determination of percentage of peripheral blood mononuclear cells bearing CD4+ and CD8+ markers was done by conventional fluorescent antibody cell sorter analysis of the mononuclear cell population. Absolute number of CD4+ lymphocytes was determined by multiplying the total lymphocyte count by the percent of mononuclear cells bearing CD4+ marker. From October 1987 to August 1991, 61 patients, 50 males and 11 females, had 65 episodes of specific pneumonia. The average age of patients was 31.4 years (range 29-59 years). The risk factors for HIV infection included intravenous drug abuse (47 patients), homosexuality (6 patients), bisexuality (3 patients) and heterosexual contact (5 patients). Before the onset of pulmonary disorders, patients were classified in the following clinical HIV-related stages: asymptomatic state (22 episodes), ARC (22 episodes) and AIDS (21 episodes). In decreasing order of frequency diagnosis of pneumonias were PCP (29 episodes), community-acquired bacterial pneumonia (16 episodes), pulmonary tuberculosis (8 episodes), nonspecific interstitial pneumonia (4 episodes), PCP and pulmonary tuberculosis (3 episodes), cytomegalovirus pneumonia (2 episodes), and one of each episode of PCP and pulmonary cryptococcosis, pulmonary candidiasis, pulmonary Kaposi's sarcoma. The mean and the standard deviation of immunologic values regarding the four primary diagnostic groups were: PCP CD4+/CD8+ 0.50 +/- 0.42, CD4+/mm3 196 +/- 190; bacterial pneumonia CD4+/CD8+ 0.53 +/- 0.44, CD4+/mm3 247 +/- 139; pulmonary tuberculosis CD4+/CD8+ 0.62 +/- 0.38, CD4+/mm3 260 +/- 170; nonspecific interstitial pneumonia CD4+/CD8 + 0.57 +/- 0.48, CD4+/mm3 240 +/- 189. No significant statistical differences with respect to CD4+/CD8 ratios and CD4+ cell counts among these diagnostic groups were found by standard analysis of variance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8492972 TI - Covering the history of nursing. PMID- 8492973 TI - Call for action on immigrant HIV exclusion policy. AB - The Coalition for Immigrant and Refugee Rights and Services in San Francisco drafted a national sign-on letter to President Clinton, urging immediate action to end the mandatory HIV testing and exclusion of immigrants to the U.S. The Coalition, with the support of the American Civil Liberties Union, has asked for our help in mobilizing a letter writing campaign during the month of March. The following is a suggested form for such a letter. PMID- 8492974 TI - Lillian Wald: connecting caring with activism. PMID- 8492975 TI - Strategies for building a representative nursing faculty. PMID- 8492976 TI - Paying our dues. PMID- 8492977 TI - Refocusing the skills laboratory. AB - Nurses often have difficulty applying theory to clinical practice. The author explores ways to which nurse educators can facilitate the transfer of theory to practice using the nursing skills laboratory. PMID- 8492978 TI - RN/BSN distance learning through microwave. AB - Audio and video interactive electronic classroom systems are one way to increase access to baccalaureate programs for working nurses who do not reside near a degree-granting university. The authors describe the impact of this microwave television system on course implementation in a registered nurse/bachelor of science in nursing program. They also discuss the implications for course design, teaching strategies, class interaction, and student achievement. PMID- 8492979 TI - Beam me up, nurse! Educational technology supports distance education. AB - The Intercollegiate Center for Nursing Education (ICNE) has recently added a second technology to its earlier distance education program. Orientation of nursing faculty to effectively use the new two-way video and audio interactive microwave system has been a challenge, and the reward for meeting that challenge is satisfied distant learners. The author discusses the planning, implementation, and evaluation of this new technology. PMID- 8492980 TI - Distance learning through audioconferencing. AB - As more students living at a distance from campus seek nursing degrees, eliminating barriers to their access will require creative solutions. The author describes the advantages and disadvantages of audioconferencing to overcome barriers of distance and how to plan, implement, and evaluate such a course. PMID- 8492981 TI - Preparing student nurses for patient education. AB - Patient education is an integral part of the nurse's responsibility. Furthermore, public awareness of health issues has greatly increased public demand for information from health professionals. The author presents some teaching strategies that can be used by nurse educators to prepare students for their future role as teachers. PMID- 8492982 TI - Public speaking: content and process evaluation of nursing students' presentations. AB - Speaking to an audience is a complex communication activity that involves many elements combining process and content skills. Mastery of these complex skills is a necessity for every professional nurse. Faculty in the school of nursing at La Salle University created the public speaking evaluation instrument (PSEI) to help students develop and refine skills that promote effective communication in public speaking. The tool guides the development of student presentations and provides them with immediate feedback on their speech. PMID- 8492983 TI - Targeting male students. PMID- 8492984 TI - Faculty development in values: need and strategy [corrected]. PMID- 8492985 TI - Allied health students and AIDS: a survey of knowledge and personal risk behaviors. PMID- 8492986 TI - Can we revolutionize nursing curriculum without liberating liberal education? No! PMID- 8492987 TI - Discipline without punishment. PMID- 8492988 TI - [Thinking about research. Ideas for a researched practice of nursing care]. PMID- 8492989 TI - [Financing health in Quebec]. PMID- 8492990 TI - [The occupational health nurse plays a hybrid role]. PMID- 8492991 TI - [New national exams for the future nurses]. PMID- 8492992 TI - [Anti-stress strategies and methods for the field of nursing care]. PMID- 8492993 TI - [Points on the orientation of nursing practice in community health centers]. PMID- 8492994 TI - [The baccalaureate in nursing sciences at the University of Quebec and Abitibi Temiscamingue]. PMID- 8492995 TI - Health care reform and the practicing obstetrician-gynecologist. PMID- 8492996 TI - Update of new risk factors and prevention of neural-tube defects. PMID- 8492997 TI - Contraceptive prevalence, reproductive health and our common future. The C. Donald Christian Memorial Lecture. PMID- 8492998 TI - Perfluorocarbon in the treatment of giant retinal tears. PMID- 8492999 TI - Risk of retinal detachment after YAG capsulotomy. PMID- 8493000 TI - Physicians' income--what's fair? PMID- 8493001 TI - Nerve fiber layer defects with normal visual fields. Do normal optic disc and normal visual field indicate absence of glaucomatous abnormality? AB - PURPOSE: When the optic disc has normal appearance with no abnormalities in routine automated perimetry, the subject is not considered to have glaucoma. The purpose of this study is to show how such patients may have localized retinal nerve fiber layer defects with corresponding functional abnormality. METHODS: The authors selected eight eyes of eight patients who had a localized retinal nerve fiber layer defect extending within a few degrees from fovea but in whom the optic disc appearance and Humphrey 30-2 visual fields were normal. Of the eight patients, three had positive family history of glaucoma, two had suspected retinal nerve fiber layer abnormality in routine eye examination, two had increased intraocular pressure (IOP), and one had advanced low-tension glaucoma in one eye with a normal fellow eye. The authors examined the central 10 degrees visual field with 1 degree resolution using Humphrey perimeter and the Ring and Centring programs of the high-pass resolution perimeter. RESULTS: A central field defect corresponding to retinal nerve fiber layer defect was found in six of eight patients: in both 10 degrees Humphrey field and Centring programs (2 eyes), in Humphrey only (2 eyes), and in Centring only (2 eyes). CONCLUSION: The results indicate that retinal nerve fiber layer photographs are helpful in diagnosing glaucoma because early glaucomatous abnormalities cannot be excluded without nerve fiber layer photography. Currently available routine perimetric examination programs do not always detect very early functional damage. PMID- 8493002 TI - Loss of visual acuity after trabeculectomy. AB - BACKGROUND: Glaucoma filtration surgery can result in loss of visual acuity by a variety of mechanisms. The existence of "wipe-out" (loss of the central visual field in the absence of other explanation) as a cause of postoperative loss of visual acuity has been debated. This study defines the incidence and etiology of visual acuity loss within 3 months of trabeculectomy. METHODS: The authors reviewed 508 eyes of 440 patients who underwent trabeculectomy to find cases of postoperative visual acuity loss (2 or more Snellen lines or a category change) and randomly selected a control group of 85 eyes to analyze the risk factors for each cause of visual acuity loss. RESULTS: Forty-two eyes (8.3%) showed loss of visual acuity after 3 months, caused mainly by lens opacification (n = 16), hypotony maculopathy (n = 6), and "wipe-out" (n = 4). Older patients (P = 0.0108), those in whom the visual field preoperatively showed macular splitting (P = 0.0084) and those who had severe hypotony (intraocular pressure [IOP] < or = 2 mmHg) on the first postoperative day (P = 0.0246) were more likely to experience "wipe-out." Older age (P = 0.0495) and shallow anterior chamber (P = 0.0003) were correlated to the development of lens opacification. Hypotony maculopathy was associated with coronary artery disease (P = 0.0397) and systemic hypertension (P = 0.0118). CONCLUSIONS: Lens opacification was the main cause of early visual acuity loss after trabeculectomy, followed by hypotony maculopathy. "Wipe-out," although rare, does exist, and older patients with advanced visual field defects are at increased risk. PMID- 8493003 TI - Prevalence, diagnostic features, and response to trabeculectomy in exfoliation glaucoma. AB - BACKGROUND: The "true" prevalence and clinical attributes of exfoliation glaucoma remain controversial. The authors studied these characteristics in glaucoma patients requiring trabeculectomy. METHODS: One hundred consecutive patients undergoing trabeculectomy for open-angle glaucoma were investigated by clinical examination (biomicroscopy and gonioscopy) and classified into three categories: exfoliation glaucoma, possible exfoliation glaucoma, and primary open-angle glaucoma (POAG). A definitive diagnosis of exfoliation glaucoma was provided by pathologic examination of iris tissue. RESULTS: All 22 patients with clinical evidence of exfoliation glaucoma and 4 of 18 patients with possible exfoliation glaucoma on clinical examination had ultrastructural evidence of exfoliation material. The prevalence of exfoliation glaucoma, therefore, was 26%. The clinical examination for the diagnosis of exfoliation glaucoma had an 85% sensitivity rate and a 100% specificity rate. In comparison with POAG, patients with exfoliation glaucoma had higher untreated intraocular pressure (IOP), higher IOP with medical therapy, and shorter duration of medical therapy. They were more often operated on for unacceptably high IOP. Exfoliation glaucoma patients exhibited significantly lower IOP after surgery. CONCLUSION: Exfoliation glaucoma is common in patients requiring trabeculectomy for open-angle glaucoma. This condition differs from POAG by a poorer response to medical therapy and a better response to trabeculectomy. PMID- 8493004 TI - Surgical management of post-traumatic angle recession glaucoma. AB - PURPOSE: The purpose of this study is to compare the results of three different drainage procedures performed for uncontrolled post-traumatic angle recession glaucoma. METHODS: A retrospective analysis was undertaken of 87 drainage procedures performed on 65 patients over an 8-year period. The results of trabeculectomy (47 procedures), Molteno single-plate implantation (20 procedures), and trabeculectomy combined with antimetabolite (20 procedures) were compared. Of those treated with antimetabolite, 11 received postoperative subconjunctival injections of 5-fluorouracil and 9 received an intraoperative application of 0.02% mitomycin C to the trabeculectomy site. RESULTS: In the group undergoing trabeculectomy with antimetabolite therapy, the intraocular pressure (IOP) drop was significantly greater, the percentage of successful cases at 3 and 6 months postoperatively was significantly higher, and the number of postoperative glaucoma medications was significantly lower than the other two groups. No statistically significant differences were found between the groups undergoing trabeculectomy without antimetabolite therapy and Molteno implantation. Of concern were three cases of late bleb infection in the group that received postoperative antimetabolite therapy. CONCLUSION: In medically uncontrolled post-traumatic angle recession glaucoma, trabeculectomy with antimetabolite therapy is the most effective surgical procedure. However, late bleb infection is a significant risk. PMID- 8493005 TI - Diurnal variation in intraocular pressure of normal-tension glaucoma eyes. AB - BACKGROUND: The nature of intraocular pressure (IOP) in normal-tension glaucoma (NTG) has not been studied in detail, although the information on the IOP is indispensable for diagnosis and treatment of NTG. METHODS: After at least six IOP measurements at daytime clinic, diurnal IOP was measured at 10:00 AM, 12:00 noon, 2:00, 4:00, 6:00, 8:00, 10:00 PM, 12:00 midnight, and at 3:00, 6:00, 8:00, and 10:00 AM by 1-day hospitalization in 118 NTG suspects. Four subjects with peak IOPs exceeding 21 mmHg were diagnosed as primary open-angle glaucoma (POAG) whose eyes all had mean clinic IOPs above 16 mmHg. The remaining 114 patients were diagnosed as having NTG, and their right eye data were used for analysis. RESULTS: The rhythmic nature of the diurnal IOP of NTG was analyzed by fitting the data to a cosine curve. In 54.4% of the eyes, the correlation between the measured IOP and the values predicted from the cosine curve was significant (r > 0.60, P < 0.05), and the equation, diurnal IOP = 13.9 + 1.7 cos 2 pi (t/24-0.40) mmHg, which was similar to that reported in normals, was obtained. Multiple regression analysis showed that the mean diurnal IOP was best predicted with the mean of the six clinic IOPs and systolic blood pressure (R2 = 0.67), and the peak diurnal IOP with the mean of six clinic IOPs (R2 = 0.50). The estimate fell within +/- 1 and +/- 2 mmHg of the actual value in 83% and 96% of the left eyes for the former and in 69% and 93% for the latter, respectively. No eyes with peak diurnal IOP exceeding 21 mmHg were overlooked with the cutoff IOP of 16 mmHg. CONCLUSION: The mean and peak diurnal IOP could be predicted with the mean of clinic IOPs. PMID- 8493006 TI - Evaluating the visual field effects of blepharoptosis using automated static perimetry. AB - BACKGROUND: Quantitation of the effects of blepharoptosis on the visual field has largely been limited to manual kinetic perimetry using a single peripheral isopter. The authors evaluated the visual dysfunction caused by blepharoptosis using automated static full-threshold perimetry. METHODS: A custom static full threshold 60 degrees test strategy on the Humphrey field analyzer was used to assess the visual fields of 20 volunteers at their normal baseline and after inducing mild and moderately severe blepharoptosis by applying gold weights to the eyelids. Threshold sensitivities were measured at points along the eight principal meridians, separated by 45 degrees, traditionally used to assess visual field impairment. RESULTS: For mild blepharoptosis, essentially all test points along the superior meridian were significantly depressed (P < 0.01), with an increase in slope secondary to greater decreases in sensitivity at more eccentric points. For moderately severe blepharoptosis, depression of the superior meridian was expectedly greater than that seen with mild blepharoptosis. Additionally, depression of the horizontal meridians and to a lesser extent the lower meridians also was noted. CONCLUSIONS: These results suggest that even mild blepharoptosis may be associated with depression of the superior visual field extending close to fixation. Ophthalmologists should be aware of the effect of blepharoptosis when testing for other ophthalmic or neurologic disorders using automated static perimetry. Full-threshold static perimetry can be used to quantitate the visual field loss associated with blepharoptosis as a means of evaluating visual impairment. PMID- 8493007 TI - Postcataract ptosis. A randomized, double-masked comparison of peribulbar and retrobulbar anesthesia. AB - PURPOSE: A randomized, double-masked study of 317 patients was conducted to determine if the incidence of postcataract ptosis is greater with retrobulbar or two-injection peribulbar injection anesthesia. METHODS: Surgery consisted of a planned extracapsular extraction with posterior chamber lens implantation, and no superior rectus bridle suture was used. Ptosis was quantitatively documented preoperatively and postoperatively at 1, 2, 5, and 90 days by the surgeon, photographically at 90 days by a masked observer, and subjectively by the patients. Postcataract ptosis was defined as a drop in the lid margin of 2 mm or greater after correcting for any change in the fellow eye. RESULTS: The incidence of ptosis at 90 days in patients given peribulbar anesthesia was 5.8% and in patients given retrobulbar anesthesia 5.5%, and this difference was not statistically significant (P = 0.90). Eighteen percent of patients in both groups reported a change in the appearance of their eyelids. There was a moderate, positive correlation among patients who reported a change in their lid position and objective measurements of ptosis. Preoperative clinical measurements of vertical lid fissure width and levator function, and the appearance of the lid crease or superior sulcus were not predictive for the development of postoperative ptosis at 90 days; the best predictor was the presence of ptosis in the immediate postoperative period. CONCLUSION: The incidence of postcataract ptosis is the same whether two injection peribulbar or retrobulbar anesthesia is used. PMID- 8493008 TI - Chronic dacryocystitis caused by Mycobacterium fortuitum. AB - PURPOSE: To characterize the clinical presentation of Mycobacterium fortuitum dacryocystitis, an unusual microbial cause of this disease. METHODS: The authors present a detailed description of a case of M. fortuitum chronic dacryocystitis and a review of the literature. FINDINGS: Although M. fortuitum is a well recognized cause of chronic keratitis and corneal ulcer, it has only been reported once previously as a cause of dacryocystitis. Multiple factors that alter the ocular environment of the host may predispose to infection with this organism. The diagnosis requires isolation of the organism in the appropriate clinical setting. The authors' case represents the first patient successfully treated with dacryocystectomy. CONCLUSION: M. fortuitum is a rare cause of chronic dacryocystitis that may respond favorably to surgical therapy alone. PMID- 8493009 TI - Dacryocystitis associated with malignant lymphoma of the lacrimal sac. AB - BACKGROUND: Tumors of the lacrimal sac are unusual, and lymphomas of the lacrimal sac are quite rare. Four patients with a history of well-differentiated, small cell lymphoma or chronic lymphocytic leukemia presented with either acute or chronic dacryocystitis and epiphora due to lymphomatous infiltration of the lacrimal sac. METHODS: All four patients underwent dacryocystorhinostomy with lacrimal sac biopsy. All tissues underwent complete histopathologic evaluation including immunohistochemical studies for cell surface markers and, in addition, were compared with previous biopsies performed for the initial diagnosis of lymphoma. FINDINGS: All biopsies demonstrated small cell well-differentiated lymphoma on histologic and immunofluorescent examination. No patient demonstrated orbital involvement on computed tomography. One patient had previously diagnosed chronic lymphocytic leukemia and one patient demonstrated diffuse lymph node involvement on postoperative systemic evaluation. All four patients underwent additional chemotherapy. No recurrence of dacryocystitis or epiphora occurred. CONCLUSION: Four patients presented with dacryocystitis secondary to lacrimal sac lymphoma. Lymphomatous lacrimal sac infiltration is an unusual cause of dacryocystitis. Biopsy of the lacrimal sac plays a diagnostically important role in dacryocystorhinostomy even in the absence of obvious tumorous involvement of the lacrimal sac mucosa. PMID- 8493010 TI - Orbital fat removal. Decompression for Graves orbitopathy. AB - BACKGROUND: Orbital decompression has been used to describe surgical procedures that remove some portion of the orbital walls to reduce pressure on the orbital contents. Substantial morbidity associated with these procedures includes infraorbital anesthesia, worsened extraocular motility, globe displacement, and blindness. The authors believe that orbital contents also may be decompressed by removing orbital fat. METHODS: Eighty-one patients with nonactive Graves orbitopathy were selected for orbital fat decompression based on the presence of proptosis and associated signs and symptoms to avoid bone removal. Soft-tissue analysis by computed tomography (CT) scan showed distended pockets of fat extending into the intraconal space, which were removed through medial-upper and lateral-lower anterior orbitotomies. Decompression with bone removal was reserved for those few patients with compressive optic neuropathy unresponsive to medical treatment and those patients with residual deforming exophthalmos after fat removal. RESULTS: One hundred fifty-eight fat decompressions were performed on 81 patients over 9 years. The authors measured an average reduction in proptosis of 1.8 mm (range, 0-6.0 mm). The greatest average reduction in proptosis (3.3 mm) was produced in patients with preoperative Hertel measurements of greater than 25.0 mm. Morbidity was limited to temporary motility impairment of the inferior oblique in two patients. CONCLUSION: The concept of orbital decompression can include removal of orbital fat to reduce proptosis, eliminate symptoms, and improve appearance with far less morbidity than when bone decompression is used as the primary decompressive procedure. PMID- 8493011 TI - Operative complications of optic nerve sheath decompression. AB - BACKGROUND: Optic nerve sheath decompression (ONSD) is a procedure that is advocated for the treatment of certain types of optic nerve dysfunction associated with progressive decline in visual function. The reported postoperative complications attributed to ONSD surgery are relatively few and predominantly transient and benign. Few postoperative vascular complications are reported. METHODS: The authors performed a retrospective review of the operative and postoperative course of 31 consecutive patients (38 eyes) undergoing ONSD surgery for various types of optic nerve dysfunction associated with progressive decline in visual acuity, visual fields, or both. The authors evaluated the reports of other investigators to ascertain the spectrum and diversity of postoperative complications associated with ONSD. RESULTS: Fifteen (40%) of the 38 eyes undergoing ONSD had postoperative complications, including temporary motility disorders (29%) and pupillary dysfunction (11%). Additionally, four eyes (11%) had postoperative vascular complications, including two central retinal artery occlusions (CRAOs), one superotemporal branch retinal artery occlusion (BRAO), and one episode of transient outer retinal ischemia. Both eyes with postoperative CRAOs had poor visual outcome. Eyes that had undergone prior ONSD were significantly more likely to have vascular complications than those without a previous operation (Fisher's exact test, P = 0.025). CONCLUSIONS: Optic nerve sheath decompression can be associated with a variety of postoperative complications, the majority of which are minor and resolve without sequelae. Other complications, such as a CRAO, can be associated with significant visual loss. The physician and patients should be aware of the potential risks of ONSD, including significant visual morbidity, when considering this form of treatment. PMID- 8493012 TI - Fellow eye abnormalities in acute unilateral optic neuritis. Experience of the optic neuritis treatment trial. AB - BACKGROUND: Visual function in the fellow eye at the onset of unilateral optic neuritis has not been systematically evaluated. The authors prospectively determined the prevalence of abnormalities in the fellow eyes of the 448 eligible patients entered into the Optic Neuritis Treatment Trial. METHODS: All patients underwent testing of visual acuity, contrast sensitivity, color vision, and visual field, as well as magnetic resonance imaging (MRI) of the brain and a neurologic examination. RESULTS: Abnormalities in the fellow eye were found on measurement of visual acuity in 13.8%, contrast sensitivity in 15.4%, color vision in 21.7%, and visual field in 48.0% of patients. The majority of the fellow eye deficits resolved over several months. A higher prevalence of MRI changes consistent with demyelination of the brain was found in patients with a past history of optic neuritis in the fellow eye compared with patients without such a history (P = 0.004). Patients with abnormal fellow eyes but no history of previous optic neuritis were no more likely to have clinical (P = 0.658) or MRI evidence (P = 0.166) of multiple sclerosis than patients with normal fellow eyes. CONCLUSIONS: The improvement of many of the visual deficits indicates that visual abnormalities detected in the fellow eye at the onset of symptomatically unilateral optic neuritis may not represent preexisting optic nerve demyelination. Whether the presence of these deficits is predictive of the development of clinical multiple sclerosis cannot be determined at this time. PMID- 8493013 TI - Perioperative choroidal hemorrhage at pars plana vitrectomy. A case-control study. AB - PURPOSE: Risk factors for choroidal hemorrhage during pars plana vitrectomy surgery are currently not well defined. The authors analyzed potential risk factors for perioperative choroidal hemorrhage at pars plana vitrectomy in a case control study. METHODS: Of 683 consecutive vitrectomy procedures, 13 cases of choroidal hemorrhage were identified in the operative or immediate postoperative period. Fifty vitrectomy controls from the same period were randomly selected and were compared with the hemorrhage cases by univariate analysis with respect to various potential risk factors. RESULTS: The incidence of choroidal hemorrhage associated with vitrectomy was 1.9%. Statistically significant risks (P < or = 0.05) included: greater age (mean, 70.9 versus 52.1 years); elevated preoperative pressure (19.9 versus 13.0 mmHg); preoperative diagnosis of rhegmatogenous retinal detachment (relative risk, 8.1); aphakic or pseudophakic status (relative risk, 5.2); and scleral buckle procedure at vitrectomy (relative risk, 12.0). Eyes with previous ocular trauma and previous vitrectomy had a reduced risk of choroidal hemorrhage. The incidence of severe visual loss (final visual acuity < 5/200) did not differ significantly from controls. CONCLUSIONS: Significant risk factors for choroidal hemorrhage are identified in this study which may help to identify patients at increased risk for this complication. Good visual outcome is possible after choroidal hemorrhage at vitrectomy (69% with visual acuity > 5/200). PMID- 8493014 TI - The role of chorioretinal biopsy in the management of posterior uveitis. AB - BACKGROUND: The ideal management of intraocular inflammation may require a tissue diagnosis. Diagnostic vitrectomy is a well-established method for acquiring such tissue. However, in some patients, the diagnostic pathology is limited to the choroid and retina and vitrectomy may yield no useful information. In such cases, a more aggressive surgical approach to obtain tissue may be useful. METHODS: The authors performed chorioretinal biopsies on seven patients with progressive chorioretinal lesions of unknown etiology. Indications for biopsy included: (1) macular-threatening lesions unresponsive to therapy, (2) suspicion of malignancy, or (3) suspicion of an infectious etiology. In all cases, it was expected that the results would alter therapy or other aspects of clinical care. Preoperative visual acuity was 20/200 or worse in each eye biopsied with one or more peripheral chorioretinal lesions present. Biopsy specimens were divided into three parts and submitted for light and electron microscopy, immunohistochemistry, and tissue culture. RESULTS: On the basis of the biopsy findings, a diagnosis of multifocal choroiditis and subretinal fibrosis was rendered in three eyes, sarcoidosis in two eyes, and viral retinitis in two eyes. Therapy was changed in five patients. Final visual acuity was unchanged or improved in five eyes. Complications included the progression of lens opacity in all eyes and the development of phthisis in one eye that was extensively diseased preoperatively. CONCLUSION: Chorioretinal biopsy may provide useful information for determining the diagnosis and guiding the subsequent management of patients with progressive chorioretinal lesions of unknown etiology. PMID- 8493015 TI - Endophthalmitis caused by the coagulase-negative staphylococci. 1. Disease spectrum and outcome. AB - PURPOSE: The coagulase-negative staphylococci are the most common causes of postoperative endophthalmitis. This study investigates the variability in the disease spectrum and visual outcome of coagulase-negative staphylococcal endophthalmitis in a large, single-center series. METHODS: Ninety consecutive cases of coagulase-negative staphylococcal endophthalmitis were investigated retrospectively from two time periods, 1978 to 1982 and 1985 to 1987, separated by a transitional period in cataract surgery technique. Using a detailed protocol, inpatient, outpatient, and microbiologic records were analyzed. Six month visual acuity results were obtained. RESULTS: Diagnosis frequently was delayed, often suspected only after hypopyon development. Thirty-seven percent of patients presented more than 1 week after the inoculating event, and 13% presented after more than 1 month. Variable asymptomatic intervals and gradually worsening inflammatory prodromes are noted. Painless endophthalmitis occurred in 16%. Non-epidermidis infections comprised 28%. With vitrectomy/intraocular antibiotic management, 38% and 68% achieved visual acuities of 20/50 and 20/400, respectively. Overall, 10% of patients developed late retinal detachments. This occurred in only 4% of patients, with endophthalmitis occurring after cataract surgery. CONCLUSION: Ophthalmologists should become familiar with the emerging concepts of delayed-onset, chronic, and often painless endophthalmitis in which the coagulase-negative staphylococci play a prominent role. PMID- 8493016 TI - Endophthalmitis caused by the coagulase-negative staphylococci. 2. Factors influencing presentation after cataract surgery. AB - PURPOSE: This study, comprising 60 patients with coagulase-negative staphylococcal endophthalmitis which occurred after cataract surgery, was designed to define the variation in disease presentation and visual outcome and to evaluate statistically the role of the primary surgery and its management. METHODS: An intensive evaluation of microbiological, inpatient, outpatient, and cataract surgery charts was made retrospectively using a standardized protocol. The predictive value of surgical, iatrogenic, and clinical factors was analyzed for their influence on defined aspects of the disease pattern and of the visual results using multiple regression models, via a stepwise technique. RESULTS: There was commonly a significant asymptomatic latent period after cataract surgery. The median diagnostic delay was 7 days; 22% of patients presented after 2 weeks and 12% after 1 month. Symptoms progressed longer than 3 days in 25% of patients. Ten percent had no pain. Clinical variation proved largely unrelated to cataract surgery events and postoperative management; bacterial factors were implicated. Good visual outcome was associated statistically with intensive topical corticosteroid in the symptomatic period, but was negatively associated with operative subconjunctival corticosteroid. CONCLUSIONS: The clinical variation in cases of postoperative coagulase-negative staphylococcal endophthalmitis poses particular problems for diagnosis in the outpatient setting. Surgical and perioperative events (except corticosteroid use) probably can be disregarded in studies of endophthalmitis management. PMID- 8493017 TI - Extracapsular cataract extraction with placement of a posterior chamber lens in patients with diabetic retinopathy. AB - PURPOSE: The authors evaluated factors that might influence the outcome of extracapsular cataract extraction with placement of a posterior chamber lens in patients with diabetic retinopathy. The factors included patient age and sex, severity of the retinopathy, preoperative laser photocoagulation, vitrectomy, and posterior capsulotomy. METHODS: The records of 109 patients who had been examined by the authors before cataract surgery were retrospectively reviewed. RESULTS: The final visual acuity in only 48% of the eyes was 20/40 or better, and 28% had 20/200 or worse visual acuity. Only 65% had an improvement in visual acuity of two or more Snellen lines. Eyes with preoperative macular edema had a poorer visual outcome than eyes without. Macular edema and ischemia accounted for 70% of the eyes with a final visual acuity of 20/50 or worse. The authors found that age was a strong predictor of final visual acuity and chances of improvement. In patients 63 years of age and younger, 58% had 20/40 or better and 81% had improved visual acuity. In patients 64 years of age and older, only 38% had 20/40 or better and only 54% were improved. Supplementary panretinal photocoagulation was required in 37% of patients who had received it preoperatively. Neovascularization of the iris developed in 6% of patients. Posterior capsulotomy did not cause an increased incidence of neovascularization of the iris or in the development or progression of proliferative retinopathy or macular edema. CONCLUSION: The prognosis of patients with diabetic retinopathy about to undergo cataract surgery, even extracapsular cataract extraction with placement of a posterior chamber lens, is guarded. PMID- 8493018 TI - Excimer laser photorefractive keratectomy for myopia. Clinical results in sighted eyes. AB - PURPOSE: To evaluate the refractive results of excimer laser photorefractive keratectomy (PRK) performed on normal, sighted myopic eyes; to assess the role of postoperative topical steroid treatment in patients with PRK; and to study the regression of effect. METHODS: An argon fluoride 193-nm excimer laser was used. Photorefractive keratectomy was performed on 420 eyes with preoperative refraction ranging from -1.25 to -7.50 diopters (D). Minimum follow-up time was 12 months, and 194 of the eyes were followed for 15 months. Postoperative treatment generally consisted of topical dexamethasone for 3 months, but in a sub study, some eyes were treated for only 5 weeks. RESULTS: Mean refraction (spherical equivalent +/- standard deviation) at 12 months was -0.04 +/- 0.84 D and at 15 months -0.22 +/- 0.78 D. At 12 months postoperatively, 86% of the eyes were within 1.00 D of emmetropia, at 15 months 87%. At 12 months, 91% of the eyes had an uncorrected visual acuity of at least 20/40, at 15 months 87%. Eyes treated with dexamethasone for 3 months regressed significantly less than those treated for only 5 weeks (P < 0.01). Dexamethasone also was effective in reversing regression later in the postoperative course. Eyes with preoperative myopia up to 4.90 D had significantly better refractive results at 12 months than eyes with myopia ranging from 5.00 to 7.50 D (P < 0.01). CONCLUSION: These data show that excimer laser PRK can correct myopia with good predictability. Results at 12 and 15 months tend to suggest stability of postoperative refraction. Regression of effect was more common in higher myopes. Topical steroids postoperatively seem to play a crucial role for the refractive result. PMID- 8493019 TI - Results of radial and astigmatic keratotomy by beginning refractive surgeons. AB - BACKGROUND: There is little information available on the results of radial and astigmatic keratotomy surgery that is performed by beginning refractive surgeons. METHODS: A retrospective review of all refractive keratotomies performed by Corneal Fellows in the University of California, Los Angeles, Department of Ophthalmology between October 1985 and October 1991 was performed. Data from all eyes with at least 3 months of follow-up were analyzed. Visual acuity, refractive error, and complication rates were compared with published case series. RESULTS: The mean preoperative spherical equivalent for the 79 eyes analyzed was -3.97 diopters (D) (range, -0.75 to -8.50 D). The mean postoperative spherical equivalent was -0.44 D (range, +1.50 to -3.88 D). The postoperative spherical equivalent was within 1.00 D of emmetropia in 85% of eyes, and uncorrected visual acuity was 20/40 or better in 94% of eyes. There were no vision-threatening complications. No patient lost more than one line of best-corrected visual acuity. CONCLUSION: Radial and astigmatic keratotomies that are performed by beginning refractive surgeons in a supervised setting can be safe and effective procedures with results comparable with those obtained by experienced refractive surgeons. PMID- 8493020 TI - Holmium laser thermokeratoplasty. AB - PURPOSE: Corneal curvature can be altered by shrinking stromal collagen with a pulsed solid-state holmium: YAG laser in a procedure termed laser thermokeratoplasty. METHODS: The authors performed laser thermokeratoplasty in 40 human cadaver eyes using a ring pattern of 32 spots, each spot having a diameter of 300 microns. RESULTS: The amount of induced corneal steepening decreased as ring diameter was increased in 1 mm increments, with 22.2 +/- 3.3 and 3.7 +/- 2.0 diopters (D) of central steepening with diameters of 3 and 7 mm, respectively. Results of histologic examination showed a cone-shaped zone of increased stromal hematoxylin uptake extending posteriorly for 90% of stromal thickness. Energy levels greater than those needed to induce topographic changes produced limited endothelial injury in rabbit corneas and, in some cases, intraocular inflammation. A computerized, finite element model of the globe demonstrated central corneal steepening as a result of heat-induced stromal contraction to a depth of 75% corneal thickness. CONCLUSIONS: These data support previous studies indicating that central corneal topography can be modified by heating corneal stroma in a controlled fashion with the mid-infrared holmium:YAG laser. PMID- 8493021 TI - Photorefraction screening in premature infants. AB - BACKGROUND: Photorefraction is a screening technique capable of detecting potentially amblyogenic ophthalmic abnormalities. This screening technique was included as part of a longitudinal outpatient follow-up program of premature infants. The purpose of this investigation is to test the applicability of this screening method in a population of infants at risk for visual compromise. METHODS: One-hundred eighty-two premature infants older than 3 months chronologic age were screened using a commercially available, off-axis photorefraction device. Ophthalmic examinations were performed concomitant with each photorefraction. In most cases, photorefractions were performed before and after administration of cycloplegic medications. All photorefractions were analyzed by an observer masked to the results of the ophthalmic examination. RESULTS: For the 182 patients, the mean birth weight and mean gestational age were 1034.5 g and 28.2 weeks, respectively. The prevalence of ophthalmic abnormalities in the study population was 18%. Sensitivity and specificity rates for the overall screening were 77% and 90%, respectively. Photorefractions were analyzable in 77% of patients studied, with the remaining 23% of our study population unsuccessfully screened. Very young infants (younger than 3 months corrected age) were particularly difficult to photograph, as evidenced by the preponderance of these patients (85%) in the nonanalyzable group. The readability of photorefractions in black infants was improved when cycloplegia was used for the photorefraction. CONCLUSION: Photorefraction screening was an acceptable method of screening for ophthalmic abnormalities in a group of premature infants. Future studies of photorefraction screening techniques in premature infants will need to improve the success rate in young infants, perhaps by improving the fixation device. PMID- 8493022 TI - The efficacy of optical and pharmacological penalization. AB - PURPOSE: Optical and pharmacological penalization of sound eyes are infrequently used alternatives to occlusion for treating amblyopia. The authors evaluated the efficacy of penalization as their primary treatment of amblyopia. METHODS: One hundred sixty-six patients underwent penalization treatment for strabismic or anisometropic amblyopia for a minimum of 3 months. Both atropine and optical penalization methods were used. RESULTS: Visual acuity improved in 67 (77%) of 87 patients treated with optical penalization. There was a significant improvement of the geometric mean visual acuity of the amblyopic eyes from 20/38 to 20/28 (P < 0.001). Visual acuity of 60 (76%) of 79 patients treated with pharmacological penalization improved. There was a significant improvement of mean visual acuity of the amblyopic eyes from 20/61 to 20/40 (P < 0.001). Neither therapy produced an instance of occlusion amblyopia. Thirteen patients discontinued therapy because of blur or discomfort. CONCLUSION: This study demonstrates that penalization methods are effective methods for the treatment of amblyopia, with a low risk of occlusion amblyopia. Patient acceptance of these methods was excellent. Penalization should be considered more often for the primary treatment of amblyopia. PMID- 8493023 TI - Congenital nonpigmented epithelial iris cyst after amniocentesis. Clinicopathologic report on two children. AB - BACKGROUND: Congenital nonpigmented epithelial iris cysts are not common. They may arise spontaneously from developmental entrapment of surface ectodermal epithelium or from occult ocular trauma prenatally or at birth. PATIENTS AND METHODS: Between 1989 and 1991, an 8-month-old child and a 6-year-old child presented with large, progressive congenital epithelial iris cysts. Both children had a maternal history of diagnostic amniocentesis after an ultrasound scan, and there was no history of postnatal ocular trauma. The cysts were successfully removed by a modified block excision and tectonic corneoscleral grafting. RESULTS: A dense adherence of the cyst wall to Descemet's membrane resembled old anterior synechiae after occult perforation of the globe in both patients. On histopathologic examination, the epithelial lining of the cysts consisted of non keratinizing stratified squamous epithelium with goblet cells resembling conjunctival epithelium. A perforating limbal scar with a corresponding break in Descemet's membrane could be detected in one eye. The long-term visual acuity of both children was encouraging, and there was no evidence of recurrence of the iris cyst during the follow-up period (average, 23 months). CONCLUSIONS: The authors conclude that the clinical and histopathologic features of these congenital iris cysts may be consistent with an occult intrauterine limbal perforation of the anterior chamber with a needle during amniocentesis. Amniocentesis, when not guided by a real-time ultrasound scan, may be a risk factor for prenatal ocular trauma, which should be considered in the differential diagnosis of congenital ocular disorders. PMID- 8493024 TI - Congenital intraocular teratoma. AB - PURPOSE: The clinical and histopathologic findings of an intraocularly located congenital teratoma are reported. METHODS: In addition to routine histologic stainings, the tissue types present and the fate of the neuroectodermal elements of the disorganized eye were analyzed by immunohistochemistry. RESULTS: An otherwise healthy baby girl was born with a large greenish mass replacing the left eye without invading the orbit. The enucleated eye showed a firm polycystic intraocular tumor filling the intraocular space. Normal sclera and a massively distended cornea enclosed the globe. Fairly normal choroid and a disorganized ciliary muscle were present, but the ciliary body and iris had not formed. The tumor was surrounded by maldeveloped remnants of the optic vesicle and consisted of derivatives of all three germinal layers such as adnexal glands, brain, choroid plexi, intestinal and respiratory epithelium, cartilage, adipose tissue, as well as smooth and skeletal muscle. DISCUSSION: The clinical history with presentation at birth, female sex of the patient, and both macroscopic and microscopic findings are typical of a benign orbital teratoma, but the intraocular location is unique. Lack of truly medulloepitheliomatous elements in this case and the absence of derivatives from three germinal layers in all previously reported teratoid medulloepitheliomas of the ciliary body exclude the latter diagnosis. The teratoma may have arisen in the orbit with subsequent entrapment within the developing eye when the embryonic fissure closed. PMID- 8493025 TI - StORQS: Washington's Statewide Obstetrical Review and Quality System: overview and provider evaluation. AB - The Foundation for Health Care Quality (Washington) used three administrative public databases and indicators recommended by the Joint Commission and the American College of Obstetrics and Gynecology to build algorithms to measure quality of obstetric care in the state of Washington. Analyses demonstrated a high degree of variability across hospitals for major processes of care such as cesarean section, vaginal birth after cesarean section, and forceps deliveries. Eighty-five percent of the participating hospitals concluded that important aspects of care were being measured. Ninety-four percent found the information useful in describing their performance compared with other hospitals. Sixty-two percent believed the information was useful for initiating quality improvement projects. Of the 25 indicators tested in the project, indicators rated as most useful were the same 10 obstetric indicators chosen by the Joint Commission after alpha testing. PMID- 8493026 TI - Evaluating the cost containment potential of clinical guidelines. AB - New expensive biotechnology products create financial as well as clinical dilemmas for hospitals. Clinical guidelines that govern the use of these new products are often viewed as the best response to these dilemmas. This article describes a prospective analysis of the impact of one new drug and the guidelines developed to control its use. A simple model of clinical decision making is used to evaluate alternative scenarios. The analysis illustrates the importance of evaluating the cost containment potential of clinical guidelines before they are implemented. PMID- 8493027 TI - Pneumonia mortality reduction and quality improvement in a community hospital. AB - Rather than explain adverse results on the basis of flawed data, a physician directed quality improvement program was initiated to improve the delivery of care to patients admitted to Forbes Health System (Monroeville, Penn) with community-acquired pneumonia. Following the introduction of standardized physician orders and modification and elimination of inefficient processes of care, the mortality rate for this infection decreased from 10.2% to 6.8%. This initial exposure to the quality improvement process led to the participation of the medical staff in other related clinical and support service initiatives. In addition, Forbes and its clinical partners are now better positioned to respond to increasing government, managed care, and consumer inquiries relating to cost and quality outcomes. Finally, this positive experience facilitated the organization's transition from inspection-based quality assessment to quality improvement activities, which should assist in efforts to meet or exceed new accreditation standards. PMID- 8493028 TI - Utilization managers in Medicare risk contract HMOs: from control to collaboration. AB - A study of utilization management (UM) practices in 13 health maintenance organizations (HMOs) with Medicare members was undertaken as part of an evaluation of the Medicare Risk Contract strategy. Although there were significant variations among HMOs, the common challenges of managing care for this particular population also led to important similarities. Most notable was the emphasis on redirecting the focus of control-oriented utilization review to promotion of continuous improvement in care management. The multiple medical and social service needs of Medicare beneficiaries have forced HMOs to cultivate close collaboration with physicians and UM personnel. Thus, UM personnel are involved throughout the continuum of care and play an important role in assisting HMOs to approach the "seam-less delivery system" ideal. HMOs report that the experience of managing care for Medicare members has made them more responsive to serving all of their members and to promoting long-term partnerships with their physicians. PMID- 8493029 TI - [In vitro study and clinical transplantation of human fetal islands of Langerhans]. AB - A simple and reliable procedure was developed for the long-term culturing and cryopreservation of human fetal pancreatic islets. The methods involved can ensure the survival and the growth capacity of fetal tissue. The long-term cultivation or cryoculturing of fetal islet tissue was applied in 23 clinical transplantatious on the basis of the experimental study. All of the diabetic patients suffered progressive retinopathy and three of them had nephropathy as well. After grafting the insulin requirement reduced significantly (39.4%) correlated with the higher serum C-peptide level (mean: 0.41 ng/ml). During the long-term follow-up (9 yrs), the graft function failed in 5 cases, while in 18 successful cases the long term graft function depended on the volume of the grafted islet mass. The results suggest that the transplantation of fetal pancreatic islet has a beneficial effect in the early stage of diabetic complications. PMID- 8493030 TI - [Retrospective biochemical study of the preventive property of antioxidants in retinopathy of prematurity]. AB - Oxygen radical injury may be one of the factors leading to Retinopathy of Prematurity. It occurs when the body's natural antioxidant capacity is overwhelmed by the free oxygen radicals produced during the perinatal period. Supposing, that premature infants may have defects in their antioxidant systems which can be detected later, even in childhood, a retrospective study of 36 patients of different ages (born prematurely) suffering from different stages of Retinopathy of Prematurity was carried out. According to our results, the signs of an acute oxidative stress could only be seen in the 3 month-old patients' erythrocyte glutathione redox system which was independent of the clinical severity of retinopathy. However, following an in vitro oxidative stress an increased susceptibility of erythrocytes was found in all our patient groups, which means, that the ratio of residual and original amounts of reduced glutathione was decreased and the amount of oxidated derivates of haemoglobin was increased. As selenium is an integral part of glutathione peroxidase enzyme, the very low selenium levels measured in all of our patient groups indicate a reduced glutathione peroxidase activity. The present study suggests, that selenium depletion even in Hungary might play an important role in the pathogenesis of Retinopathy of Prematurity. PMID- 8493031 TI - [Distribution of ABO groups in patients undergoing heart surgery]. AB - The authors examined retrospectively the AB0 blood groups of 3982 patients who underwent cardiac surgery. There were 3392 cases of acquired heart disease, 590 congenital heart disease. They found significant difference in the total patients blood groups distribution in contrast to the control group. Further significant differences were found in the following cases: 1. total male patients, 2. acquired heart disease (both males and females), 3. isolated aortic valve disease (both males and females), 4. ischaemic heart disease (only males). In regard to the total patients group, their findings suggest significant difference between the males and females blood group distribution. This observation was peculiar to the acquired heart diseases only. They conclude that there is a positive correlation between AB0 blood groups and certain cardiac diseases, most notably, ischaemic heart disease in male patients. PMID- 8493032 TI - [Obstructive cardiomyopathy, caused by amyloidosis, associated with bone marrow myeloma]. AB - A case of a 40-year-old female is reported. Her symptoms started with abdominal complaints, loss of weight, general weakness, then gradually polyneuropathy, worsening hypotonia and systolic heart murmur developed. The bone marrow showed 20-25% infiltration by myeloma. An IgG lambda type paraproteinaemia was diagnosed using immunelectrophoresis. The ejection systolic murmur was caused by restrictive cardiomyopathy--characteristic of primary amyloidosis--with obstruction of the outflow tract of the left ventricle. Echocardiographic changes took 11 months to develop. The patient's status became dominated by severe hypotonia and she died as a result of heart failure. The post mortem examination confirmed amyloidosis with myeloma. Histopathological examination of the myocardium, coronary and other arteries revealed severe changes with AL-type amyloid deposits. The case demonstrates that amyloidosis can lead not only to restrictive cardiomyopathy but obstruction of the outflow tract of the left ventricle. PMID- 8493033 TI - Developments in the health service: the role of the Department of Health. PMID- 8493034 TI - The Swedish modification of the tracheostomy tube to permit speech. AB - Over the last 20 years the Respiratory Unit at Danderyd Hospital, Sweden has treated and rehabilitated more than 90 patients on domiciliary ventilation, the majority of whom require night-time ventilation. Sixteen patients (11 men and 5 women) with high spinal cord lesions have been treated. Of these 16 patients, 9 are using diaphragmatic pacing. Every patient has a customised tube. If the patient can use diaphragmatic pacing the tube, as a rule, is single fenestrated. In patients using the ventilator full time, the tube is made to fit snugly in the trachea. When such a tube fits 'as a bullet in its tube' there is no need for a cuff. The patient has adequate ventilation and the small leak around the tube also permits good speech function. Sometimes a PEEP-valve is used to get a better voice. PMID- 8493035 TI - The role of functional electrical stimulation in the rehabilitation of patients with incomplete spinal cord injury--observed benefits during gait studies. AB - The benefits of a functional electrical stimulation (FES) gait programme were assessed in a group of 6 incomplete spinal cord injured subjects. Measurements were made of quadriceps spasticity, lower limb muscle strength, postural stability in standing, spatial and temporal values of gait, physiological cost of gait and independence in activities of daily living. The subjects were assessed before commencement of the programme and after a period of gait training using FES. The benefits derived as a result of the FES gait programme included a reduction in quadriceps tone, an increase in voluntary muscle strength, a decrease in the physiological cost of gait and an increase in stride length. PMID- 8493036 TI - Preclinical trial of 4-aminopyridine in patients with chronic spinal cord injury. AB - 4-Aminopyridine (4-AP) is a K+ channel blocking agent that enhances nerve conduction through areas of demyelination by prolonging the duration of the action potential and increasing the safety factor for conduction. We have investigated the effects of 4-AP (24 mg total dose-intravenous) in 6 patients with spinal cord injury (3 complete, 3 incomplete) with the intent of overcoming central conduction block, or slowing, due to demyelination. Vital signs remained stable and only mild side effects were noted. The 3 patients with incomplete injuries all demonstrated enhanced volitional EMG interference patterns and one patient exhibited restored toe movements. The changes were reversed on drug washout. There were no changes in segmental reflex activities. These results are consistent with those obtained from 4-AP trials with animal models of spinal cord injury, showing modest therapeutic benefit attributable to enhanced central conduction. PMID- 8493037 TI - Assessing selfcare status in quadriplegia: comparison of the quadriplegia index of function (QIF) and the functional independence measure (FIM). AB - The purpose of this study was to compare the quadriplegia index of function (QIF) to the functional independence measure (FIM) in assessing the daily performance of selfcare activities by individuals with cervical spinal cord injury. This study evaluated feeding, grooming and bathing activities in 22 C4-C7, Frankel A-D spinal cord injury patients between 3 and 12 months postinjury. The manual muscle test (MMT) was performed on 17 of these subjects during the same window of time as the QIF and the FIM. An upper extremity motor score (UEMS) was derived from the MMT. In order to relate motor power to functional ability, the UEMS was used as a measure of neurological function to test the hypothesis that the QIF scores are more highly correlated to motor power than are the FIM scores for this population. Spearman coefficients were calculated to correlate the QIF, the FIM and the UEMS. For the bathing and grooming categories, both the QIF and the FIM showed significant and similar correlations to the UEMS. For the feeding category, however, the QIF had a significantly better correlation to the UEMS than did the FIM (Rho = 0.90 vs 0.53, p < 0.01). Use of the QIF feeding scale may allow the detection of changes in function as individuals recover that the FIM scale would miss. Further evaluation of the remaining selfcare and mobility scales is needed. Modification of the FIM with more sensitive portions of the QIF would improve the discriminative ability of outcome studies and program evaluations. PMID- 8493038 TI - Blockage of indwelling urinary catheters: the roles of urinary composition, the catheter, medication and diet. AB - The aim of this work was to study factors related to the blockage of indwelling urinary catheters. There were 40 patients with indwelling catheters, 20 of whom had catheters that blocked frequently. The other 20 were trouble free at the time of our study. The type and gauge of catheter and frequency of events were recorded. Urine samples for biochemical analysis comprised 24-hour collections, morning specimens on up to 10 different days and 5-8 samples at different times during the same day. Chemical analysis of debris removed from blocked catheters showed it to consist of mixed phosphates of calcium and magnesium, thus being similar to urinary stones that may be seen in spinal cord injury patients. Patients with frequent catheter blockage had significantly elevated urinary pH and ammonium and calcium concentrations. Discriminant analysis gave 78-94% separation of catheter blocking patients from nonblockers depending on the type of sample. We conclude that bacterial urease activity and urinary calcium concentration are the most important factors in catheter blockage. Elevation of urinary pH following ingestion of effervescent preparations, drug- or diet induced increases in urinary calcium or magnesium excretion and inadequate or erratic fluid intake may be avoidable contributing factors. PMID- 8493039 TI - Continent urinary diversion and diverting colostomy in the therapy of non-healing pressure sores in paraplegic patients. AB - Immobilization and subsequent sacral decubitus or pressure sore formation is a danger faced by the paraplegic. We report on 4 patients treated with non-healing pressure sores. Three male patients had decubiti eroding into the posterior urethra and bladder neck area. One female patient had bladder neck and urethral loss secondary to Foley catheter erosion and a sacral pressure sore. All 4 had non-healing decubiti secondary to urinary contamination and, in addition, gross fecal contamination in the male patients. All patients failed previous muscular flaps and urinary diversion per suprapubic tube. In the male patients, suprapubic continent urinary diversion included bladder neck mobilization, closure of the distal urethra by oversewing and patching with bovine dura, and augmentation of the bladder with a Miami pouch. Fecal diversion was provided with a sigmoid colostomy. In the female patient, continent diversion was performed by forming a Miami pouch. Total diversion allowed healing of the pressure sores and provided a simpler method of personal hygiene. Details of the diversion and case studies will be presented. PMID- 8493040 TI - Clinical aspects of neurolathyrism in Unnao, India. AB - To study the clinical picture of lathyrism in Unnao, India and compare it with that reported from other endemic areas, 41 patients from Unnao were studied. Their mean age was 42.9 years (range 22-85) and the mean duration of the illness was 17.1 years (range 2-30). They had been regularly consuming Lathyrus Sativus (LS). The patients complained of walking difficulty due to weakness and leg stiffness (32 each), and of frequency of micturition (4). Gait abnormalities included spastic gait (24), toe walking (18) and the necessary use of walking sticks (13). Weakness was mild to moderate, and was less prominent than was spasticity. In 8 patients the physical signs were asymmetrical. Peripheral neuropathy was present in only one patient, but muscle atrophy and widespread fasciculations were not found. A higher frequency of peripheral neuropathy and lower motor neuron involvement has been reported from Bangladesh and Israel. Severe spasticity in the absence of prominent weakness in lathyrism may be due to the involvement of certain specific groups of corticospinal fibres. PMID- 8493041 TI - Physical performance of elite wheelchair basketball players in armcranking ergometry and in selected wheeling tasks. AB - This study compared the aerobic and the anaerobic performance of 11 elite Israeli wheelchair basketball players in arm ergometric tests and corresponding wheeling tasks, derived from basketball practice. The ergometric tests included a continuous aerobic maximal peak work capacity test (PWCmax), and a 30-second arm all-out anaerobic test of mean anaerobic capacity (MANC) and peak anaerobic power (PANP). The wheeling tasks included a 428 meter race, slalom and 6-minute endurance race. We examined the relationship of performance variables to personal variables, age, bodyweight and classification as athletes. The results were analysed by Spearman correlation tables, revealing the following: (1) HRmax (maximal heart rate) correlated highly (r = .884-.962) with performance in all wheeling tasks; (2) no relationship was found between variables in the arm ergometric tests and variables in the wheeling tasks; (3) bodyweight correlated significantly with MANC and PWCmax (r = .817 and .783 respectively). This relationship was better than the other independent variables (classification and age). It is concluded that HRmax can be used for performance evaluation in wheelchair basketball practice, and that arm ergometric work capacity has only limited predictive value of performance in wheeling tasks. PMID- 8493042 TI - Cervical spinal cord atrophy associated with spina bifida. AB - We treated three patients with spina bifida who had atrophy of the cervical spinal cord. One patient presented with a gradually progressive paresis of the upper right extremity, and two patients developed tetraparesis. MRI (magnetic resonance imaging) of the cervical spine demonstrated cord atrophy with enlargement of the subarachnoid space. The three patients were treated by releasing the tethered spinal cord in the lumbosacral area. Two of the three patients had neurological recovery soon after the operation, but this was transient and was followed by later deterioration; and the third patient showed no recovery. The transient recovery suggests that the tethering in the lumbosacral region affects the entire spinal cord and causes atrophy of the cervical spinal cord. PMID- 8493043 TI - Serum rheumatoid factors in spinal cord injury patients. AB - The rheumatoid factor (RF) levels of IgM-RF and IgG-RF types in sera from patients with spinal cord injuries (SCI) and osteochondrosis were investigated by ELISA. According to the findings in the late stages of the disease, SCI patients showed 46% seropositiveness for IgG-RF and 40% for IgM-RF. Patients with fresh central nervous system (CNS) injuries were 12% and 14% seropositive, respectively. Patients with osteochondrosis exhibited 33% seropositiveness for IgG-RF. The determination of serum RF enables us to identify the systemic body lesion in the SCI late stages as a rheumatoid disease. These data support the conclusion that RF determination is a reliable serological indicator of the severity of a patient's traumatic disease. PMID- 8493044 TI - Nurse entrepreneur ... what are you waiting for? AB - With the wealth of knowledge and experience many nurses have, they could become successful nurse entrepreneurs. This article presents several possibilities for nurses to consider: independent practitioners, case managers, writers, seminar leaders, and video producers. Useful tips on marketing yourself are included. PMID- 8493045 TI - Revision surgery in adult scoliosis patients. AB - Surgical management of the scoliosis patient has evolved significantly in recent years. We are now seeing patients who were operated on 15-20 years ago return with problems distal to the fusion. These adults have unique problems that need to be managed by many disciplines. This article describes current problems in the adult scoliosis patients who have had previous surgery, current treatments, and nursing management of these patients. PMID- 8493046 TI - A look at nursing's agenda for health care reform. AB - Nursing organizations have united behind a program for restructuring health care. Nursing's Agenda for Health Care Reform proposes 1) universal health care insurance coverage for a wide range of health care services; 2) greater freedom of consumer choice and access to a variety of providers (including nurses); and 3) incentives to reduce costs, including managed care and a shift in emphasis toward preventive health care services. PMID- 8493047 TI - Physiologic and behavioral responses of children receiving intermittent intravenous morphine following orthopaedic surgery. AB - The purpose of this study was to describe the physiologic and behavioral responses of children receiving intermittent intravenous morphine following orthopaedic surgery. The nonrandomized sample was made up of 29 children between the ages of 6 months and 11 years. Subjects received morphine IV push over 5 minutes (0.1 mg/kg body weight) every 3-4 hours prn. Heart rate, respiratory rate, transcutaneous CO2 and oxygen saturation were collected prior to administration and then at 5-minute intervals for a total of 25 minutes. Pain cue behaviors were assessed prior to morphine and at 25 minutes after intravenous injection, the time of peak analgesia. Subjects received a total of 199 doses of morphine. Physiologic data were analyzed using repeated measures of variance with Waller-Duncan multiple comparison procedures. The results of this study support the safe and effective use of intravenous morphine in children 6 months to 11 years following orthopaedic surgery. PMID- 8493048 TI - Prevention and management of dance injuries. AB - Dancing is the loftiest, the most moving, the most beautiful of the arts, because it is no mere translation or abstraction from life; it is life itself (Ellis, 1923). Despite the "magic" that professional dancers display, they, too, are subject to physical limitations. As an old German proverb suggests, "If you want to dance, you must pay the piper." In a recent interview, Samuel Bennett of Ballet Chicago speculated that many dance injuries are the result of attempting to achieve a physical ideal that probably doesn't exist. The following is an overview of dance injuries, their prevention, and their treatment. The focus is on ballet. PMID- 8493049 TI - Uncertainty and appraisal of uncertainty in women with rheumatoid arthritis. AB - This study examined relationships among length of illness, degree of uncertainty, and appraisal of uncertainty in women with rheumatoid arthritis. Twenty-three subjects completed the Mishel Uncertainty in Illness Scale and an Appraisal Scale. No association was found between length of illness and uncertainty or its appraisal, but uncertainty was significantly correlated with appraisal of uncertainty as danger. High uncertainty was predictive of appraisal of uncertainty as danger. Nurses who are aware of uncertainty experienced by their patients may be better able to recognize and support the individual's coping efforts. PMID- 8493050 TI - Empowering nurses through nursing ethics committees. AB - Nurses are patient advocates who often feel powerless when implementing that role in ethical situations. One strategy to empower nurses in their advocacy role is the development and use of nursing ethics committees within health care institutions. PMID- 8493051 TI - Medications for a growing concern: tuberculosis. PMID- 8493052 TI - Getting nursing's message into the media. AB - Nursing has a story to tell--a story about competent caring professional men and women who can and are making a difference daily in the health of the nation. Orthopaedic nurses can help tell the story by being informed, telling the stories, writing, networking, and monitoring. PMID- 8493053 TI - Preventing teenage pregnancy: some questions to be answered and some answers to be questioned. PMID- 8493054 TI - The effects of sexuality education on adolescent sexual activity. PMID- 8493055 TI - Newborn consequences of teenage pregnancies. PMID- 8493056 TI - Teenage pregnancy is preventable--a challenge to our society. PMID- 8493057 TI - Teenage pregnancy--one of our nation's most challenging dilemmas. PMID- 8493058 TI - Adolescent pregnancy: occurrence and consequences. PMID- 8493059 TI - The pediatrician's role in assisting teenagers to avoid the consequences of adolescent pregnancy. AB - There are ways in which the practicing pediatrician can help adolescent prevent pregnancy or improve the outcome of pregnancy. Clearly, each practitioner will have to decide what services will work best within his or her practice as well as for the community. PMID- 8493060 TI - Nutrition during teenage pregnancy. AB - The nutritional needs of pregnant adolescents are the greatest at a time when it is most difficult to meet them. Dieting, skipping meals, snacking, eating away from home, consuming fast foods, and trying unconventional diets are common eating behaviors among adolescents, which relate to their changing lifestyles of increased independence, busy schedules, search for self-identity, peer influence, group conformity, and body image dissatisfaction. Total nutritional needs of pregnant adolescents who are at least 2-year post-menarche are similar to those of pregnant adults. But, because of their poor dietary habits, they usually enter pregnancy with reduced nutrient stores and increased risk of nutritional deficiencies. All pregnant teens, therefore, should have their dietary habits assessed along with special dietary counseling, and vitamin-mineral supplements should be recommended if their usual nutritional intake is below standard. Also, the weight-gain pattern should be monitored to ensure that energy intakes are sufficient to support a gain of about 0.4 kg (1 lb) per week in the second and third trimester. PMID- 8493061 TI - Learning disabilities. AB - Although the major manifestations of learning disabilities are expressed in the classroom, the pediatrician has several important roles to play. Identification may be achieved in the early school years by systematic observation of the child's neurodevelopment and school progress. Confirmation of the diagnosis is the most commonly assumed role. Interpretation and explanation of learning disabilities to the parents and child follow. The goals of treatment of learning disabilities are achievement of academic competence, treatment of associated deficits, and prevention of adverse mental health outcomes. The long-term relationship between the family and pediatrician facilitates the performance of longitudinal monitoring to ensure that the program is accomplishing its goals and that outcome is optimal. PMID- 8493062 TI - Mental retardation. AB - In children with mental retardation, development is altered so that adaptive and cognitive skills are significantly deficient. Causes of mental retardation are varied and include newborn trauma, infectious diseases, chromosomal abnormalities, metabolic disorders, and environmental toxins. In many cases, however, the cause of mental retardation remains unknown. Most affected children have mild retardation and are able to achieve economic and social independence as adults. Early identification by the pediatrician of a developmental delay is important to ensure appropriate treatment and to enable the child to develop all of his or her capabilities. PMID- 8493063 TI - Down syndrome. AB - Down syndrome remains one of the most common causes of mental retardation. Although knowledge of pathogenesis remains incomplete, recent molecular biologic techniques have identified regions of the 21st chromosome critical for expression of the Down syndrome phenotype, and animal models have helped elucidate the origins of the neurochemical and neuropathologic abnormalities. There also has been an improved understanding of the spectrum of medical complications of this disorder and the need for anticipatory management, including the search for atlantoaxial subluxation and hypothyroidism. With its increased risk of Alzheimer disease, Down syndrome is proving to be a useful model for studying aging. Accompanying greater knowledge has been improved functional outcome. Better medical care has made individuals with Down syndrome healthier; remaining at home through childhood has increased their cognitive function; and availability of increased numbers of group homes and supported employment opportunities has permitted the young adult with Down syndrome to live a more independent and full life. In this climate, the role of the pediatrician in early intervention and anticipatory guidance cannot be overemphasized. PMID- 8493064 TI - Cerebral palsy. AB - Over the last century, our understanding of cerebral palsy has broadened. For example, we now know that it results more commonly from prenatal abnormalities than from perinatal difficulties. Yet, in most cases we are still no closer to understanding the operant mechanism of injury or how the injury results in the expressed motor disorder. Hopefully, the strides being made in neurodevelopmental physiology and neurotransmitter communication will help elucidate the mechanism of injury in cerebral palsy and thereby lead to methods of prevention. Meanwhile, comprehensive clinical evaluation and treatment and periodic reassessment will help tailor strategies to the individual needs of the child. This should enable the child with cerebral palsy to optimize his or her function in society. PMID- 8493065 TI - Traumatic brain injury in children. AB - Head trauma is a common occurrence in childhood, and the spectrum of its consequences is broad. Depending on the severity, type, and location of the injury, outcome may range from complete recovery in children with mild injuries to severe disability in children with more serious injuries. Potential deficits are multiple and include motor, communicative, cognitive, sensory, behavioral, and emotional problems. Optimizing function in those areas is the goal of neurorehabilitation, and this may require medical, therapeutic, and educational interventions. An even more important goal is prevention, and here, too, the pediatrician can play an essential role. PMID- 8493066 TI - Autism and pervasive developmental disorders. AB - Autism and pervasive developmental disorder, not otherwise specified represent a complex developmental disability in which clinical signs include language delay, social unrelatedness, and unusual or restricted interests. Gradually a better understanding of these disorders as being neurologically-based developmental disorders with multiple etiologies has replaced the idea of emotional disturbance. Although pervasive developmental disorders are rare, the potentially devastating effects make early recognition by pediatricians imperative. Yet, despite promising treatment advances in education, communication technology, behavior treatments, and pharmacology, the prognosis for these disorders remains guarded. PMID- 8493067 TI - Orthopedic management of children with cerebral palsy. AB - Children with cerebral palsy are a diverse group. Many variables affect their orthopedic care, including age, type and severity of involvement, functional abilities, previous treatment, and access to treatment. The overall goals of orthopedic management include the detection of specific orthopedic problems at an early stage when simple and more effective treatment options may be instituted. Orthopedic intervention currently is almost more of an art than a science. With continued efforts and research, it is hoped that new and better ways will be found to improve the care of these children. PMID- 8493068 TI - Growing up with Patricia. AB - Parents of a child with special needs to describe their experiences coping with the various challenges to the family as they grew up together. They discuss coping strategies, shared responsibility, and the trials of dealing with physicians, schools, and social service agencies. They talk about advocating for their child and preparing for the transition to adulthood. Their story is followed by a commentary by a social worker who suggests techniques that pediatricians can use to empower families of children with disabilities to optimize outcome. PMID- 8493069 TI - [Effect and complications of embolization therapy using absolute ethanol for renal arteriovenous malformation]. AB - Transcatheter embolization therapy using absolute ethanol was accomplished in six patients with renal arteriovenous malformation. The effect of this therapy was considered to be good, because none of the patients has experienced recurrent hematuria. It is necessary to avoid the back flow of absolute ethanol. One patient had the particular complication of hydronephrosis caused by the incidental injection of absolute ethanol into the ureteral artery. PMID- 8493070 TI - [Subtraction and dynamic MR images of breast cancer]. AB - The purpose of this study was to evaluate the diagnostic effectiveness of subtraction and dynamic MR imaging in patients with breast masses. In 23 breast cancers and six fibroadenomas, spin echo T1 images were obtained at 0.2 Tesla before and every minute after the intravenous injection of Gd-DTPA (0.1 or 0.2 mmol/kg). Subtraction images were obtained sequentially on the CRT monitor. All breast masses were enhanced after gadolinium and stood out as bright lesions on subtraction images. The tumor margin and its extension were more precisely evaluated on subtraction MR images than on conventional postcontrast MR images. Breast cancer showed a characteristic time-intensity curve with an early peak, in contrast to fibroadenoma, which showed a gradual increase in signal intensity. Subtraction MR imaging is a simple method for the evaluation of breast masses, and further, the time-intensity curve obtained by dynamic study is helpful in the differential diagnosis of lesions. PMID- 8493071 TI - [Ankylosing spondylitis with acute anterior uveitis--correlation between HLA-B27 and clinical and radiologic findings]. AB - Six cases of ankylosing spondylitis (AS) complicated with acute anterior uveitis (AAU) were reviewed. Clinical and radiologic findings of these cases were correlated with HLA-B27. All the patients were men; four of them were HLA-B27 positive, and two were B27 negative. The average age of onset was younger in B27+ patients than in B27- patients. Ophthalmologic study showed no definite difference in inflammatory change of AAU between B27+ patients and B27- patients. AAU in B27+ patients was completely cured in three months. A history of low back pain was more apparent in B27+ than in B27- patients. Three out of four B27+ patients showed complete bony ankylosis in sacroiliac joints, whereas no ankylosis was seen in B27- patients. CT scan was useful to demonstrate sacroilitis in cases with equivocal radiologic findings. Spondylitic changes were more extensive in B27+ than in B27- patients. The results support the concept that HLA-B27+ AS and B27- AS are different entities with similar phenotypic expression, and HLA-B27 is an arthritogenic gene in the Japanese population as well. PMID- 8493072 TI - [Transcatheter hepatic arterial embolization for the treatment of blunt hepatic injury]. AB - To examine the indications of transcatheter arterial embolization (TAE) for blunt hepatic injury, angiographic images, CT images and medical records were reviewed. Hepatic angiography was performed in 30 patients with blunt hepatic injury. Sixteen of them who underwent TAE therapy immediately after angiography formed the TAE(+)group, while the 14 patients who were not followed by TAE formed the TAE(-)group. Angiographic extravasation of the contrast medium was confirmed in 14 of 16 patients in the TAE(+)group. On CT scan, the most common finding in the TAE(+)group was a deep hepatic laceration, which was classified as type III according to the criteria of the Japanese association for the surgery of trauma. Hemoperitoneum and fresh hematoma were visualized in most of the TAE(+)group. The preoperative hemodynamics of the TAE(+)group were markedly unstable, but were significantly improved after TAE therapy. No major complications were encountered during or after TAE. These results suggested that TAE was an effective therapeutic procedure for the control of blunt hepatic injury in patients associated with unstable hemodynamics, deep hepatic laceration shown by CT scan and extravasation confirmed by angiography. PMID- 8493073 TI - [Staging of rectal cancer: assessment with Gd-DTPA enhanced MR imaging]. AB - This study was designed to assess the value of Gd-DTPA enhanced imaging in the staging of rectal carcinoma. Twenty-five patients were prospectively evaluated with MR imaging using a 1.5 Tesla unit. Based on the results of a barium study and/or digital examination, a balloon catheter was inserted to the level of the lesion before examination. Both T1- and T2-weighted images and Gd-DTPA enhanced images were obtained in all patients, and Gd-DTPA enhanced fat-saturation images were obtained in 11 patients. When both T1- and T2-weighted images were used, 24% of tumors were ill defined. However, when Gd-DTPA and Gd-DTPA enhanced fat saturation imaging was added, all tumors were well defined and the quality of the images increased. There was no significant difference between images in the detection of muscular invasion. In the detection of perirectal fat invasion, however Gd-DTPA fat-saturation imaging showed increased sensitivity. Nevertheless, it also decreased specificity, so there was no significant difference between images. In the detection of metastatic lymph nodes, Gd-DTPA enhanced and Gd-DTPA enhanced fat-saturation imaging were not useful. Tumor detection using Gd-DTPA enhanced fat-saturation images was excellent. However, the accuracy of staging was not improved by supplemental Gd-DTPA enhancement. PMID- 8493074 TI - [A new treatment method of idiopathic renal bleeding--experimental and clinical study of renal arterial infusion of a mixture with autologous blood and iopamidol]. AB - The efficacy and safety of a new treatment of idiopathic renal bleeding, by infusing a mixture of autologous blood and Iopamidol into the renal artery was studied experimentally and clinically. When using a rabbit in our experiment we injected a mixture of Iopamidol (370mgI/ml) and autologous blood in a volume of 1 ml into the renal artery. In a case study using 51Cr-labelled RBC, 3% of the RBC was retained in the kidney for 30 minutes. In a histological study RBCs were found in peritubular capillaries for 60 minutes after injection, and no organic changes were found in the glomerulus and tubular cells. In 6 patients with idiopathic renal bleeding, a mixture of patients blood (10ml) and Iopamidol (10ml) was infused into the affected renal artery. In all cases the bleeding side was left. In 5 cases even microscopic hematuria was not found during the follow up period. No complications such as the increase of serum creatinine and BUN has occurred. The mechanism of the disappearance of hematuria is still unclear, however, temporary occlusion of the renal microcirculation has a close relationship to the hemostasis. PMID- 8493075 TI - [Clinical significance of CT in evaluation of the gastrocolic trunk and its tributaries]. AB - The gastrocolic trunk (GT), consists of the veins from stomach, duodenum, pancreas and colon, passes transversely in front of the head of the pancreas and drains to the superior mesenteric vein at the lebel of the uncus. Pancreatic and/or portal venous pathology may cause dilatation or occlusion of the GT. The purpose of this study is to clarify the usefulness of X-ray computed tomography (CT) for evaluation of the GT and its tributaries in the diagnosis of pancreatic disease. The CT examinations of 176 patients (97 with pancreatic disease, 79 without pancreatic or liver disease for comparison) were reviewed retrospectively. In the comparison group, a normal GT was identified in 81% of CT scans with 5mm thick sections. Abnormal findings of the GT and its tributaries were seen in 30 cases with the involvement(occlusion or stenosis) of the portal venous system in the group of pancreatic diseases. The GTs were occluded in 17 cases with involvement of GT or SMV and dilated in 5 cases with involvement of the portal vein, SMV, or splenic vein by pancreatic diseases. In 3 cases, GTs were minimally dilated without abnormality of the portal venous system. The right gastroepiploic veins were dilated in 15 cases with splenic vein obstruction (5 patients), GT obstruction (6), SMV stenosis (3), stenosis of main portal vein (1). Assessment of the GT and its tributaries on CT would be useful for evaluation of the extension of the pancreatic disease. PMID- 8493076 TI - [Clinical experiences in using ITC silastic detachable balloons--report on 30 cases with various neurovascular diseases]. AB - As defective balloons often lead to disasters, reliable detachable balloons have long been eagerly awaited. We had the opportunity of using ITC detachable balloons on 30 cases with various neurovascular diseases. No defective balloon was found during in vitro testing done immediately prior to their placement in the patient's vascular system. Moreover, there was no premature detachment during catheter manipulation or early deflation within several weeks after detachment. Both immediate and long term follow up showed balloon embolization would be the first choice for various direct arteriovenous fistulae. Also, anatomically inaccessible aneurysms with small necks, less than 1 cc in volume, could be successfully treated by detachable balloons. However, detachable balloons are not ideal embolic material for large and giant aneurysms. In conclusion, when used by properly trained personnel, ITC silastic detachable balloons are a safe, easy to use and reliable option. PMID- 8493077 TI - [Radiation therapy for superficial type esophageal carcinoma]. AB - During the period from 1984 through 1991, fifteen patients with superficial esophageal carcinoma were treated with radiation therapy. The clinical stage of these patients was I in 13 cases and IV in two cases. We analyzed the treatment results of 13 patients with stage I disease. Seven patients were treated with external irradiation only and six patients with external irradiation plus high dose rate intracavitary irradiation. The survival rates at one, two and five years were 73.3%, 73.3% and 30.6%, respectively. The relapse-free survival rates at one, two and five years were 76.9%, 76.9% and 76.9%, respectively. Combination chemotherapy and combined therapy with intracavitary irradiation did not improve the local control rate or survival. At present, six patients have already died. The cause of death was uncontrolled primary lesion in one, radiation-induced esophageal ulcer in one, other causes in three and unknown cause in one patient. Local control was achieved in 84.6%(11/13). Radiation therapy for superficial esophageal carcinoma seems as effective as surgical therapy and may become a curative alternative. PMID- 8493078 TI - [Results of electron beam irradiation for tongue cancer]. AB - One hundred and eighty three patients with squamous-cell carcinoma of the tongue were treated with electron beam irradiation at the Dept. of Radiology, Nihon University School of Medicine, from 1967 to 1988. We analyzed the therapeutic results of the investigation to find out indications of squamous-cell carcinoma of the tongue to see if it could be treated by intra-oral cone irradiation with electron beam (IOC). The patients were restaged, as follows: stage I, 38 cases: stage II, 64 cases: stage III, 58 cases: stage IV, 23 cases. There were 113 males and 70 females, ranging in age from 18 to 87 years old. IOC was applied for T 1 or smaller T 2 cases. External neck irradiation and IOC were combined for larger T 2, T 3 or T 4 cases. The two-year local-control rates for primary lesions with the present method were 85% for T 1, 73% for T 2, and 58% for T 3. There were no two-year local-control cases for T 4. Clinical feature of the tumor were classified into tumourous type, small ulcerating type, and large ulcerating type. The two-year local-control rates were as follows: 80% for tumorous types, 68% for small ulcerating types and 53% for large ulcerating types. Uneven fractionated irradiation was performed on 144 cases and even fractionated irradiation was performed on 39 cases. The two-year local-control rates were as follows: 68% for uneven fractionated irradiation cases, 61% for even fractionated irradiation. In T 2 and T 3 cases, the two-year local-control rates were as follows: 77%, 63% for uneven fractionated irradiation cases, 56%, 40% for even fractionated irradiation cases. The two-year local-control rates were increased by uneven fractionated irradiation for T 2, T 3 cases (P < 0.05). We analyzed the therapeutic results in details for T 3 cases. T 3 patients were classified into two categories according to tumor size (category 1: long axis X short axis > 1000mm2: category 2: long axis X short axis < or = 1000mm2). The two-year local-control rates were 48% for category 1, and 72% for category 2. T 3 patients were classified into two categories according to clinical feature of the tumor (tumors with ulcers and tumors without ulcers). The two-year local-control rates were 43% with ulcers, and 74% without ulcers. The actuarial five-year survival rates were 92% for stage I, 72% for stage II, 67% for stage III, and 12% for stage IV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8493079 TI - [Determination of the point position for brachytherapy from the shift-projection method using the least squares method and geometrical solutions]. AB - We have derived formulas by the least squares method and six sets of geometrical solutions for calculating the position for brachytherapy from shift-projection images on one or two films. There are four types of expression for each coordinate in both methods, the shift-film technique with double exposures on a film and the stereo-shift technique with two films. Some geometrical solutions for the shift-film technique are equal to well-known conventional formulas. In the case of the stereo-shift technique, each conventional formula for the two coordinates is equal to the mean of the two geometrical solutions of each coordinate, and the one for the other coordinate is equal to one of the geometrical solutions. Formulas for the shift-film technique can be easily reduced to those for the stereo-shift technique. The error of the position calculated by the least squares method was the smallest among all the formulas for the shift-film technique in simulation. PMID- 8493080 TI - [Usefulness of 2D FLASH multislice dynamic MR imaging for evaluation of parametrial invasion in cervical carcinoma]. AB - Twenty seconds and 3 minutes after starting rapid injection of Gd-DTPA, multislice dynamic (MD) images were obtained with the 2 dimension fast low-angle shot (2D FLASH) technique. Four of 5 cervical carcinomas showed high signal intensity in the early dynamic phase (20 seconds), so they were readily distinguished from the myometrium that were not enhanced in the same phase. For evaluation of parametrial invasion, MD study showed better contrast between the tumor and the parametrium than did T2-weighted images because the tumor demonstrated a high signal intensity similar to that of the parameterium on T2 weighted images. MD images were able to scan the entire tumor especially in progressive cases and to evaluate the hemodynamics of the tumor. Therefore, MD imaging seemed to be useful for evaluation of parametrial invasion in cervical carcinomas. PMID- 8493081 TI - [Transthoracic percutaneous ethanol injection for the liver]. AB - Fourteen normal rats were received with percutaneous ethanol injection (PEI) in the subphrenic region of the liver, using a 22G fine needle, via the thoracic cage. The procedure was successful in all rats. Minor complications were observed in 3 rats: these included pneumothorax, hemorrhage, and pleural effusion. However all complications had disappeared in the follow up CT one week after the procedure. The transthoracic approach is a useful and safe method of PEI for the subphrenic region of the liver. PMID- 8493082 TI - [Advantages of intravascular ultrasound--preliminary experience in patients with peripheral and renal vascular disease]. AB - Intravascular ultrasound (IVUS) is a new method in which endovascular images are obtained from a catheter inserted into an artery. We uses IVUS during PTA of iliac and renal artery, and examined its effectiveness. Three layers are well defined in normal arterial wall. Calcified deposits are recognized as a combination of strong echo and acoustic shadow. The absolute cross sectional area of patent lumen and atherosclerotic plaque can be calculated. IVUS is very effective for the assessment of PTA. The increased caliber of arteries following PTA is caused by the over stretching of the media rather than the compression of atheroma. PMID- 8493083 TI - [Image-transmission of radiotherapy planning using 64kbps-ISDN videophone]. AB - We carried out the image-transmission using the 64kbps-ISDN and two terminals of the videophone installed in Osaka Teishin Hospital and Department of Radiation Oncology, Biomedical Research Center, Osaka University Medical School. The frame speeds (sec./frame) of the videophone are 1.2 for standard resolution with 320 x 200 matrix and 5.0 for high resolution with 640 x 400 matrix. Although the image with 640 x 400 matrix is not enough for the radiation diagnosis such as the chest radiogram, the image is useful for the radiation therapy planning. This system is easy to operate, and will be widely distributed in near future. PMID- 8493084 TI - [Usefulness of 201T1C1-SPECT in the evaluation of radiation and chemotherapy for brain tumors]. AB - We investigated the usefulness of Thallium-201 chloride single photon emission computed tomography (T1-SPECT) in the evaluation of radiation and chemotherapy for brain tumors. The subjects were 9 cases (10 tumors) of malignant astrocytomas. T1-SPECT was performed before and immediately after irradiation and/or intraarterial infusion of ACNU. In 5 of 10 tumors, T1-index already changed 1 or 2 months before tumor size changed on the CT. Our results suggested that T1-SPECT was useful for evaluating the viability of tumor. PMID- 8493085 TI - Focus on health care reform. PMID- 8493086 TI - So you think you're not hooked. PMID- 8493087 TI - Synthesis and antibody-mediated detection of oligonucleotides containing multiple 2,4-dinitrophenyl reporter groups. AB - A series of non-nucleoside-based 2,4-dinitrophenyl (DNP) phosphoramidites have been prepared and used in the multiple labelling of oligonucleotides during solid phase synthesis. The length of spacer arm between the DNP label and the oligonucleotide phosphate backbone, and the number of attached DNP groups have both been varied in order to determine the optimum conditions for anti-DNP antibody binding. Detection using enzyme-linked colorimetric techniques showed sensitivity equivalent to that obtainable using biotinylated oligonucleotides. PMID- 8493088 TI - Translational control by a long range RNA-RNA interaction; a basepair substitution analysis. AB - One of the two mechanisms that regulate expression of the replicase cistron in the single stranded RNA coliphages is translational coupling. This mechanism prevents ribosomes from binding at the start of the replicase cistron unless the upstream coat cistron is being translated. Genetic analysis had identified a maximal region of 132 nucleotides in the coat gene over which ribosomes should pass to activate the replicase start. Subsequent deletion studies in our laboratory had further narrowed down the regulatory region to 12 nucleotides. Here, we identify a long-distance RNA-RNA interaction of 6 base pairs as the basis of the translational polarity. The 3' side of the complementarity region is located in the coat-replicase intercistronic region, some 20 nucleotides before the start codon of the replicase. The 5' side encodes amino acids 31 and 32 of the coat protein. Mutations that disrupt the long-range interaction abolish the translational coupling. Repair of basepairing by second site base substitutions restores translational coupling. PMID- 8493089 TI - Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B. AB - A powerful chemical modification procedure has been developed to define determinants of DNA recognition by the p50 subunit of NF-kappa B. Differential labelling with [14C] iodoacetate has identified a conserved cysteine residue, Cys62, that was protected from modification by the presence of an oligonucleotide containing the specific recognition site of the protein. To determine the importance of this cysteine residue, each of the conserved cysteines in p50 was changed to serine and the DNA binding properties of the mutant proteins determined. Scatchard analysis indicated that the C62S mutant bound to its DNA recognition site with a 10-fold larger dissociation constant than the wild type protein, while the other two mutants bound with an intermediate affinity. Dissociation rate constant measurements correlated well with the dissociation constants for the wild type, C119S, and C273S p50 proteins, whereas the p50 C62S DNA complex dissociated anomalously quickly. Competition analyses with oligonucleotide variants of the DNA recognition site and nonspecific E. coli DNA revealed that the C62S p50 mutant had an altered DNA binding site specificity and was impaired in its ability to discriminate between specific and non-specific DNA. Thus the sulphydryl group of Cys62 is an important determinant of DNA recognition by the p50 subunit of NF-kappa B. PMID- 8493090 TI - High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors. AB - The promoter region of the mouse CCAAT-Enhancer Binding Protein (C/EBP alpha) gene is capable of directing high levels of expression of reporter constructs in various cell lines, albeit even in cells that do not express their endogenous C/EBP alpha gene. To understand the molecular mechanisms underlying this ubiquitous expression, we have characterized the promoter region of the mouse C/EBP alpha gene by a variety of in vitro and in vivo methods. We show that three sites related in sequence to USF, BTE and C/EBP binding sites and present in promoter region -350/+3, are recognized by proteins from rat liver nuclear extracts. The sequence of the C/EBP alpha promoter that includes the USF binding site is also capable of forming stable complexes with purified Myc+Max heterodimers and mutation of this site drastically reduces transcription of C/EBP alpha promoter luciferase constructs both in liver and non liver cell lines. In addition, we identify three novel protein-binding sites two of which display similarity to NF-1 and a NF kappa B binding sites. The region located between nucleotides -197 and -178 forms several heat-stable complexes with liver nuclear proteins in vitro which are recognized mainly by antibodies specific for C/EBP alpha. Furthermore, transient expression of C/EBP alpha and to a lesser extent C/EBP beta expression vectors, results in transactivation of a cotransfected C/EBP alpha promoter-luciferase reporter construct. These experiments support the notion that the C/EBP alpha gene is regulated by C/EBP alpha but other C/EBP related proteins may also be involved. PMID- 8493091 TI - Thermodynamic stability and drug-binding properties of oligodeoxyribonucleotide duplexes containing 3-deazaadenine:thymine base pairs. AB - We have used ultraviolet melting techniques to study the effect on stability of incorporating the nucleoside analogue 2'-deoxy-3-deazaadenosine (d3cA) into the duplex 5'-d(CGCAATCG)-3'-d(GCGTTAGC). Our results demonstrate that the successive replacement of dA by d3CA increasingly destabilises the duplex. The destabilising effect of this analogue is considerably enhanced as the pH is lowered and the results are consistent with protonation of 3-deazaadenine (probably at N-1) contributing to duplex destablisation. Surprisingly, the incorporation of d3CA does not significantly affect the binding of distamycin-A. PMID- 8493092 TI - Cloning and characterization of a naturally occurring antisense RNA to human thymidylate synthase mRNA. AB - Based upon reverse transcription and polymerase chain reaction results with human KB cell RNA, a cDNA (i.e., 3'rTS1, 1557 nt) with complementarity to thymidylate synthase mRNA was cloned and sequenced. Northern blot analysis showed that 3'rTS1 corresponded to a cytoplasmic 1.8 kb RNA found in several tumor cell lines. The remaining 5'region of this antisense RNA was cloned by a RACE (Rapid Amplification of cDNA Ends) procedure. A full length cDNA (i.e., rTS, 1811 nt) was generated by splicing 3'rTS1 with RACE-generated cDNA. rTS RNA is likely a mRNA that contains four open reading frames. Based upon sequence analysis of the RACE cDNAs and the rTS cDNA, rTS RNA is likely processed from a gene containing at least six introns. Northern blot analysis indicates rTS RNA is expressed in a variety of human tumor cell lines and an aberrant from is expressed in a methotrexate-cell line. PMID- 8493093 TI - The 35-kilodalton protein gene (p35) of Autographa californica nuclear polyhedrosis virus and the neomycin resistance gene provide dominant selection of recombinant baculoviruses. AB - Autographa californica nuclear polyhedrosis virus (AcMNPV) recombinants were constructed to test the effectiveness of the AcMNPV 35-kilodalton protein gene (35K gene) and the bacterial neomycin resistance gene (neo) as dominant selectable markers for baculoviruses. Insertion of the AcMNPV apoptosis suppressor gene (p35) into the genome of p35-deletion mutants inhibited premature host cell death and increased virus yields up to 1200-fold at low multiplicities in Spodoptera frugiperda (SF21) cell cultures. When placed under control of an early virus promoter, the bacterial neomycin resistance gene (neo) restored multiplication of AcMNPV in the same cells treated with concentrations of the antibiotic G418 that inhibited wild-type virus growth greater than 1000-fold. The selectivity of these dominant markers was compared by serial passage of recombinant virus mixtures. After four passages, the proportion of p35-containing virus increased as much as 2,000,000-fold relative to deletion mutants, whereas the proportion of neo-containing viruses increased 500-fold relative to wild-type virus under G418 selection. The strength and utility of p35 as a selectable marker was further demonstrated by the construction of AcMNPV expression vectors using polyhedrin-based transfer plasmids that contain p35. Recombinant viruses with foreign gene insertions at the polyhedrin locus accounted for 15 to 30% of the transfection progeny. The proportion of desired viruses was increased to greater than 90% by linearizing the parental virus DNA at the intended site of recombination prior to transfection. These results indicate that p35 and neo facilitate the selection of baculovirus recombinants and that p35, in particular, is an effective marker for the generation of AcMNPV expression vectors. PMID- 8493094 TI - Isolation of cDNA encoding a binding protein specific to 5'-phosphorylated single stranded DNA with G-rich sequences. AB - We have isolated the cDNA encoding a binding protein to the sequence motif of the immunoglobulin S mu region by the southwestern method. The binding protein designated S mu bp-2 specifically binds to 5'-phosphorylated single-stranded DNA containing 5'-G and GGGG stretches. The amino acid sequence deduced from the cDNA sequence showed that the S mu bp-2 belongs to the putative helicase superfamily which is involved in replication, recombination and repair. Expression of S mu bp 2 mRNA is ubiquitous and augmented in spleen cells stimulated with lipopolysaccharide and interleukin 4 which also induce class switching. The S mu bp-2 gene is conserved among vertebrates. Possible involvement of S mu bp-2 in class switching is discussed. PMID- 8493095 TI - Conformational polymorphism in G-tetraplex structures: strand reversal by base flipover or sugar flipover. AB - Guanine rich sequences adopt a variety of four stranded structures, which differ in strand orientation and conformation about the glycosidic bond even though they are all stabilised by Hoogsteen hydrogen bonded guanine tetrads. Detailed model building and molecular mechanics calculations have been carried out to investigate various possible conformations of guanines along a strand and different possible orientations of guanine strands in a G-tetraplex structure. It is found that for an oligo G stretch per se, a parallel four stranded structure with all guanines in anti conformation is favoured over other possible tetraplex structures. Hence an alternating syn-anti arrangement of guanines along a strand is likely to occur only in folded back tetraplex structures with antiparallel G strands. Our study provides a theoretical rationale for the observed alternation of glycosidic conformation and the inverted stacking arrangement arising from base flipover, in antiparallel G-tetraplex structures and also highlights the various structural features arising due to different types of strand orientations. The molecular mechanics calculations help in elucidating the various interactions which stabilize different G-tetraplex structures and indicate that screening of phosphate charge by counterions could have a dramatic effect on groove width in these four stranded structures. PMID- 8493096 TI - A repetitive DNA sequence associated with the centromeres of Chironomus pallidivittatus. AB - A clone containing centromere-associated DNA from Chironomus pallidivittatus was obtained by microdissection-microcloning. It hybridizes to the centromeric end of one chromosome and exclusively to regions in the three remaining, metacentric chromosomes to which centromeres have previously been localized on cytological grounds. In the metacentric positions the hybridization can be assigned to thin bands. The clone contains 155bp tandem repeats and short flanking regions represented in all of the centromeres. Titration experiments show that the four centromeres together contain 200kb of 155bp repeat per genome. In a line of tissue culture cells the amounts are increased by a factor 1.5-2, resulting in proportionately extended arrays of tandem repeats. Each repeat contains two invertrepeats surrounding a region containing only AT base pairs, a feature with some similarity to functionally essential elements in the Saccharomyces cerevisiae centromere. PMID- 8493097 TI - The organization of internal telomeric repeats in the polytene chromosomes of the hypotrichous ciliate Stylonychia lemnae. AB - There exist about 1000-1500 internal telomeric sequences per haploid genome in the polytene chromosomes of the hypotrichous ciliate Stylonychia lemnae. All these telomeric repeats are contained in a very conserved element. This element consists of two 2 kb direct repeats flanking a 2.6 kb sequence. Immediately adjacent to one of the repeats a 18mer C4A4C4A4C2 telomeric sequence is localized. Sequences homologous to macronuclear DNA follow 180 bp downstream of the C4A4-bloc. These macronuclear homologous sequences are flanked by the second direct repeat. The possible origin and function of these telomere containing elements is discussed. PMID- 8493098 TI - Effect of the non-conserved N-terminus on the DNA binding activity of the yeast TATA binding protein. AB - We have studied the DNA binding activity of recombinant yeast TATA Binding Protein (TBP) with particular interest in the role played by the non-conserved N terminal domain. By comparing the DNA binding activity of wild type yeast TBP with a mutant form of TBP that lacks the non-conserved N-terminal domain (TBP delta 57), we have determined that the N-terminus of TBP alters both the shape and the stability of the TBP-DNA complex. Measurements of the DNA bending angle indicate that the N-terminus enhances the bending of the DNA that is induced by TBP binding and greatly destabilizes the TBP-DNA complex during native gel electrophoresis. In solution, the N-terminus has only a slight effect on the equilibrium dissociation constant and the dissociation rate constant. However, the N-terminal domain reduces the association rate constant in a temperature dependent manner and increases the apparent activation energy of the TBP-DNA complex formation by 3 kcal/mole. These data suggest that a conformational change involving the N-terminus of TBP may be one of the isomerization steps in the formation of a stable TBP-DNA complex. PMID- 8493099 TI - Domain 5 interacts with domain 6 and influences the second transesterification reaction of group II intron self-splicing. AB - The role of domain 5 (d5) from the self-splicing group II intron 5 gamma of the COXI gene of yeast mitochondrial DNA in branching and 3' splice site utilization has been studied using a substrate transcript lacking d5 (delta d5 RNA). This RNA is completely unreactive in vitro, but releases 5' exon by hydrolysis under various reaction conditions when d5 RNA is added in trans. Under an extreme reaction condition, some accurate branching and splicing occur. Much more efficient use of a 3' splice site is obtained when delta d5 RNA is complemented by a transcript containing the wild-type domains 5 and 6 plus the 3' exon. While most delta d5 RNA molecules in that protocol still react by hydrolysis at the 5' splice site, the branching that occurs uses only the d6 tethered to d5 that is provided in trans. The use of this d6 and the 3' splice site also linked to d5, along with the observed indifference to the other d6 and 3' splice site resident in the delta d5 RNA, indicates that d5 plays a key role in positioning d6 for the first reaction step as well as in 3' splice site use. Two models for the manner by which d5 interacts with d6 are discussed. PMID- 8493100 TI - Recognition of distinct HLA-DQA1 promoter elements by a single nuclear factor containing Jun and Fos or antigenically related proteins. AB - The activity of MHC class II promoters depends upon conserved regulatory signals one of which, the extended X-box, contains in its X2 subregion a sequence related to the cAMP response element, CRE and to the TPA response element, TRE. Accordingly, X2 is recognized by the AP-1 factor and by other c-Jun or c-Fos containing heterodimers. We report that the X-box dependent promoter activity of the HLA-DQA1 gene is down-modulated by an array of DNA elements each of which represented twice either in an invertedly or directly repeated orientation. In this frame, we describe a nuclear binding factor, namely DBF, promiscuously interacting with two of these additional signals, delta and sigma, and with a portion of the X-box, namely the X-core, devoid of X2. The presence of a single factor recognizing divergent DNA sequences was indicated by the finding that these activities were co-eluted from a heparin-Sepharose column and from DNA affinity columns carrying different DNA binding sites as ligands. Competition experiments made with oligonucleotides representing wild type and mutant DNA elements showed that each DNA element specifically inhibited the binding of the others, supporting the contention that DBF is involved in recognition of different targets. Furthermore, we found that DBF also exhibits CRE/TRE binding activity and that this activity can be competed out by addition of an excess of sigma, delta and X-core oligonucleotides. Anti-Jun peptide and anti-Fos peptide antibodies blocked not only the binding activity of DBF, but also its X-core and sigma binding; this blockade was removed by the addition of the Jun or Fos peptides against which the antibodies had been raised. In vitro synthesized Jun/Fos was able to bind to all these boxes, albeit with seemingly different affinities. The cooperativity of DBF interactions may explain the modulation of the X-box dependent promoter activity mediated by the accessory DNA elements described here. PMID- 8493101 TI - Analysis of effects of tRNA:message stability on frameshift frequency at the Escherichia coli RF2 programmed frameshift site. AB - The codon that is in-frame prior to +1 frameshifting at the E.coli prfB (RF2 gene) frameshift site is randomized to create thirty-two variants. These alleles vary 1000-fold in frameshift-dependent expression in fusions to lacZ. Frameshifting is more frequent at sites where the in-frame codon ends in uridine, as if third position wobble pairs to message uridine facilitate slippage into the +1 frame. Consistent with other studies of programmed frameshift sites, efficient frameshifting depends on stable message:tRNA base pairs after rephasing. For complexes with mispairs, frameshift frequency depends on the nature, number, and position of mispairs. Central purine:purine mispairs are especially inhibitory. Relative stabilities of +1 rephased complexes are estimated from published data on the stabilities of tRNA:tRNA complexes. Stability correlates with frameshifting over its entire range, which suggests that stability is an important determinant of the probability of translation of the rephased complex. PMID- 8493102 TI - Thermal stability of DNA adducts induced by cyanomorpholinoadriamycin in vitro. AB - The Adriamycin derivative, cyanomorpholinoadriamycin (CMA) was reacted with DNA in vitro to form apparent interstrand crosslinks. The extent of interstrand crosslink formation was monitored by a gel electrophoresis assay and maximal crosslinking of DNA was observed within 1 hr with 5 microM of drug. The interstrand crosslinks were heat labile, with a midpoint melting temperature of 70 degrees C (10 min exposure to heat) in 45% formamide. When CMA-induced adducts were detected as blockages of lambda-exonuclease, 12 blockage sites were observed with 8 being prior to 5'-GG sequences, one prior to 5'-CC, one prior to 5'-GC and 2 at unresolved combinations of these sequences. These exonuclease-detected blockages reveal the same sites of CMA-induced crosslinking as detected by in vitro transcription footprinting and primer-extension blockages on single strand DNA, where the blockages at 5'-GG and 5'-CC were identified as sites of intrastrand crosslinking and the 5'-GC blockage as a probable site of interstrand crosslinking. The thermal stability of both types of crosslink (10 min exposure to heat) ranged from 63-70 degrees C at individual sites. High levels of adduct were detected with poly (dG-dC) but not with poly (dI-dC). These results suggest adduct formation involving an aminal linkage between the 3 position of the morpholino moiety and N2 of guanine. PMID- 8493103 TI - Transactivation of mouse insulin-like growth factor II (IGF-II) gene promoters by the AP-1 complex. AB - The mouse insulin-like growth factor II gene (Igf2) is transcribed from three promoters (P1, P2 and P3), and is expressed in a tissue-specific and developmentally regulated fashion; however, little information is available on the transcription factors controlling Igf2 expression. The AP-1 complex is a transcription factor involved in the regulation of a variety of genes, including those encoding certain growth factors. We show that Igf2 P3 is transactivated by AP-1 in a transient expression assay, and that this effect is mediated through two non-consensus AP-1 binding sites characterised by DNA-protein interaction studies. Mutational analysis indicates these sites are required for AP-1 responsiveness and full promoter activity. PMID- 8493104 TI - Study of multiple fibrillarin mRNAs reveals that 3' end formation in Schizosaccharomyces pombe is sensitive to cold shock. AB - Fibrillarin is a nucleolar protein which is associated with small nucleolar RNAs, and is required for pre-rRNA processing. We have cloned and characterized the gene encoding fibrillarin in the fission yeast Schizosaccharomyces pombe and we have followed its expression under various conditions. Fission yeast fibrillarin is a 305 amino-acid protein which appears to be highly conserved throughout evolution. In Xenopus, human or Saccharomyces cerevisiae, a single fibrillarin mRNA is detected while, in S. pombe a single copy gene encodes different mRNAs which differ at the 3' ends. Under normal growth conditions, two mRNAs of 1.1 and 1.35 kb are detected with the 1.1 kb being the most abundant. Both the total amount and relative abundance of these two mRNAs are strongly affected by exposure to low temperature, namely the 1.1 kb mRNA almost disappears while the 1.35 kb is less markedly diminished. A new species of 3.2 kb accumulates in the cell, which contains an unusually long 3' untranslated region of 2 kb. We have found that exposure of the cells to a cold shock has a profound effect on 3' end formation in S.pombe since the transcription of several other mRNAs is also capable of skipping the normal 3' end site to terminate at a further downstream site. PMID- 8493105 TI - Ribonuclease III cleavage of a bacteriophage T7 processing signal. Divalent cation specificity, and specific anion effects. AB - Escherichia coli ribonuclease III, purified to homogeneity from an overexpressing bacterial strain, exhibits a high catalytic efficiency and thermostable processing activity in vitro. The RNase III-catalyzed cleavage of a 47 nucleotide substrate (R1.1 RNA), based on the bacteriophage T7 R1.1 processing signal, follows substrate saturation kinetics, with a Km of 0.26 microM, and kcat of 7.7 min.-1 (37 degrees C, in buffer containing 250 mM potassium glutamate and 10 mM MgCl2). Mn2+ and Co2+ can support the enzymatic cleavage of the R1.1 RNA canonical site, and both metal ions exhibit concentration dependences similar to that of Mg2+. Mn2+ and Co2+ in addition promote enzymatic cleavage of a secondary site in R1.1 RNA, which is proposed to result from the altered hydrolytic activity of the metalloenzyme (RNase III 'star' activity), exhibiting a broadened cleavage specificity. Neither Ca2+ nor Zn2+ support RNase III processing, and Zn2+ moreover inhibits the Mg(2+)-dependent enzymatic reaction without blocking substrate binding. RNase III does not require monovalent salt for processing activity; however, the in vitro reactivity pattern is influenced by the monovalent salt concentration, as well as type of anion. First, R1.1 RNA secondary site cleavage increases as the salt concentration is lowered, perhaps reflecting enhanced enzyme binding to substrate. Second, the substitution of glutamate anion for chloride anion extends the salt concentration range within which efficient processing occurs. Third, fluoride anion inhibits RNase III catalyzed cleavage, by a mechanism which does not involve inhibition of substrate binding. PMID- 8493106 TI - Transcription by SP6 RNA polymerase exhibits an ATP dependence that is influenced by promoter topology. AB - Transcription of linearized DNA templates by SP6 RNA polymerase requires a higher concentration of ATP than of the other three nucleotides. This requirement is not shared by T7 RNA polymerase. The ATP requirement is partially relieved when the SP6 template is supercoiled but not when it is relaxed circular DNA. The effect of supercoiling is eliminated by replacement of the A.T rich sequence downstream from the SP6 promoter with a G.C rich sequence. Examination of the reaction products indicates that the ATP dependence of transcription from a linear template is not due to an ATPase activity or to the premature termination of transcription at low ATP concentration. These data suggest that the initiation of transcription by SP6 RNA polymerase requires partial denaturation of the template in the promoter-proximal region, and that this requirement can be satisfied by negative supercoiling or by increasing the ATP concentration. ATP also reduces, but does not eliminate, the abortive transcription that leads to the production of short, prematurely terminated transcripts by SP6 polymerase from supercoiled templates. PMID- 8493107 TI - Algorithms and software tools for ordering clone libraries: application to the mapping of the genome of Schizosaccharomyces pombe. AB - A complete set of software tools to aid the physical mapping of a genome has been developed and successfully applied to the genomic mapping of the fission yeast Schizosaccharomyces pombe. Two approaches were used for ordering single-copy hybridisation probes: one was based on the simulated annealing algorithm to order all probes, and another on inferring the minimum-spanning subset of the probes using a heuristic filtering procedure. Both algorithms produced almost identical maps, with minor differences in the order of repetitive probes and those having identical hybridisation patterns. A separate algorithm fitted the clones to the established probe order. Approaches for handling experimental noise and repetitive elements are discussed. In addition to these programs and the database management software, tools for visualizing and editing the data are described. The issues of combining the information from different libraries are addressed. Also, ways of handling multiple-copy probes and non-hybridisation data are discussed. PMID- 8493108 TI - Molecular analysis of the PHO81 gene of Saccharomyces cerevisiae. AB - The PHO81 gene product is a positive regulatory factor required for the synthesis of the phosphate repressible acid phosphatase (encoded by the PHO5 gene) in Saccharomyces cerevisiae. Genetic analysis has suggested that PHO81 may be the signal acceptor molecule; however, the biochemical function of the PHO81 gene product is not known. We have cloned the PHO81 gene and sequenced the promoter. A PHO81-LacZ fusion was shown to be a valid reporter since its expression is regulated by the level of inorganic phosphate and is controlled by the same regulatory factors that regulate PHO5 expression. To elucidate the mechanism by which PHO81 functions, we have isolated and cloned dominant mutations in the PHO81 gene which confer constitutive synthesis of acid phosphatase. We have demonstrated that overexpression of the negative regulatory factor, PHO80, but not the negative regulatory factor PHO85, partially blocks the constitutive acid phosphatase synthesis in a strain containing a dominant constitutive allele of PHO81. This suggests that PHO81 may function by interacting with PHO80 or that these molecules compete for the same target. PMID- 8493109 TI - A new trinuclear complex of platinum and iron efficiently promotes cleavage of plasmid DNA. AB - The compound [[Pt(trpy)]2Arg-EDTA]+ is synthesized in five steps, purified, and characterized by 1H, 13C, and 195Pt NMR spectroscopy, mass spectrometry, UV-vis spectrophotometry, and elemental analysis. The binuclear [[(Pt(trpy)]2Arg]3+ moiety binds to double-stranded DNA, and the chelating EDTA moiety holds metal cations. In the presence of ferrous ions and the reductant dithiothreitol, the new compound cleaves DNA. It cleaves a single strand in the pBR322 plasmid nearly as efficiently as methidiumrpropyl-EDTA (MPE), and it cleaves a restriction fragment of the XP10 plasmid nonselectively and more efficiently than [Fe(EDTA)]2 . The mechanism of cleavage was studied in control experiments involving different transition-metal ions, superoxide dismutase, catalase, glucose oxidase with glucose, metal-sequestering agents, and deaeration. These experiments indicate that adventitious iron and copper ions, superoxide anion, and hydrogen peroxide are not involved and that dioxygen is required. The cleavage apparently is done by hydroxyl radicals generated in the vicinity of the DNA molecule. The reagent [[Pt(trypy)]2Arg-EDTA]+ differs from methidiumpropyl-EDTA in not containing an intercalator. This difference in binding modes between the binuclear platinum(II) complex and the planar heterocycle may cause useful differences between the two reagents in cleavage of nucleic acids. PMID- 8493110 TI - The murine Sox-4 protein is encoded on a single exon. PMID- 8493111 TI - Location of the Bacillus subtilis sbcD gene downstream of addAB, the analogues of E. coli recBC. PMID- 8493112 TI - Nucleotide sequence analysis of the rRNA transcription unit of a pathogenic Entamoeba histolytica strain HM-1:IMSS. PMID- 8493113 TI - Nucleotide sequence of human cDNA encoding eukaryotic initiation factor 4AI. PMID- 8493114 TI - Plant cDNA homologue to rat insulinoma gene encoding ribosomal protein S15. PMID- 8493115 TI - Heterogeneity in the polyglutamine tract of the glucocorticoid receptor from different rat strains. PMID- 8493116 TI - Vspl methylase belongs to m6A-gamma class of adenine methylases. PMID- 8493117 TI - Absolute quantification of target DNA: a simple competitive PCR for efficient analysis of multiple samples. PMID- 8493118 TI - Sensitivity of HincII to CpG methylation. PMID- 8493119 TI - Pre-hiring HIV test 'invades privacy'. PMID- 8493120 TI - What is the future for learning disability nursing? PMID- 8493121 TI - What is the future for learning disability nursing? PMID- 8493122 TI - What is the future for learning disability nursing? PMID- 8493123 TI - What is the future for learning disability nursing? PMID- 8493124 TI - What is the future for learning disability nursing? PMID- 8493125 TI - Positively Parker Street. PMID- 8493126 TI - Scanning for trouble? PMID- 8493127 TI - Painful prejudice. PMID- 8493128 TI - Body politic. Bleak prospects. PMID- 8493129 TI - Complementary medicine. Fringe benefits. PMID- 8493130 TI - Complementary medicine. Healthy alternatives? PMID- 8493131 TI - Substance misuse--prime movers. PMID- 8493132 TI - Substance misuse--withdrawing gracefully. PMID- 8493133 TI - Male delivery. PMID- 8493134 TI - Primary nursing--your choice. PMID- 8493135 TI - Midwifery--weighing the placenta. PMID- 8493136 TI - A question of faith. Interview by Daloni Carlisle. PMID- 8493137 TI - Professional development. Preparation for change. PMID- 8493138 TI - GP fundholding. Funds of opportunity. PMID- 8493139 TI - Assessing the effects of aromatic oils. PMID- 8493141 TI - Infusion therapy--lifelines. PMID- 8493140 TI - Call for full inquiry into needlestick case. PMID- 8493142 TI - Prisoners to take part in HIV surveys. PMID- 8493143 TI - Preparing future nurses: some relevant issues. PMID- 8493144 TI - Nursing education for 21st century: needs and challenges. PMID- 8493145 TI - Protecting, promoting and supporting breast feeding: the special role of maternity services. PMID- 8493146 TI - The biology of anterior cruciate ligament reconstructions. AB - Ligaments, including the anterior cruciate ligament (ACL), have a limited biological response to injury. The same healing process affects graft tissues used to reconstruct the ACL. These biological processes interact with mechanical forces to transform the grafts into tissues, which are expected to functionally replace the ACL. Although these grafts may undergo "ligamentization," they may not undergo "ACL-ization." Further study of the important relationship between these biological and biomechanical interactions is warranted. PMID- 8493147 TI - Imaging modalities for assessing the anterior cruciate ligament deficient knee. PMID- 8493148 TI - Intraoperative complications of ACL surgery: avoidance and management. PMID- 8493149 TI - Intraarticular ACL reconstruction using the patellar tendon: arthroscopic technique. AB - Endoscopic ACL reconstruction using the bone-patellar tendon-bone autograft has been shown to have good, reliable results. The procedure provides excellent reproducible fixation immediately and allows for early aggressive rehabilitation that includes range of motion, strengthening, and rapid return to sports. PMID- 8493150 TI - Semitendinosus tendon anterior cruciate ligament reconstruction with LAD augmentation. PMID- 8493151 TI - Soft tissue coverage for the upper extremity. AB - Soft tissue coverage of the upper extremity continues to be a challenging and evolving field. The expeditious and reliable methods of soft tissue coverage currently in use are discussed with reference to their shortcomings and advantages. For soft tissue coverage of fingertip injuries, open treatment or local flaps from the hand remain the mainstay of treatment. For dorsal and volar hand defects, distal axial flaps, such as the groin flap or microvascular tissue transfer, are utilized most commonly. For large defects proximal to the wrist, trunk axial pattern flaps, microvascular transfer, or the radial forearm flap have the greatest utility. Finally, technical points necessary for the success of some of the flaps are discussed. PMID- 8493152 TI - Association of Fabry's disease with femoral head avascular necrosis. PMID- 8493153 TI - Pancreatic osteoarthropathy with unusually destructive sequelae. PMID- 8493154 TI - A cavernous hemangioma presenting as a large calcific hypothenar mass. PMID- 8493155 TI - Bilateral capitellar steroid-induced avascular necrosis. PMID- 8493156 TI - A controlled method of closed reduction of total hip dislocation. PMID- 8493157 TI - Radiologic case study. Osteomyelitis of the clavicle. PMID- 8493158 TI - Pigmenting pityriasis alba. AB - We conducted a prospective study of 20 patients with pigmenting pityriasis alba (PPA) over a period of two years. Characteristic morphology revealed a central zone of bluish hyperpigmentation surrounded by a hypopigmented, slightly scaly halo of variable width. All patients displayed lesions on the face. Concomitant extrafacial involvement was uncommon. A significant finding was an associated dermatophyte infection in 13 patients (65%). These patients all received griseofulvin 10 mg/kg/day for eight weeks, resulting in the resolution of PPA in seven within 4 to 20 weeks. These were also treated with 1% hydrocortisone. Biopsy specimens from two patients showed similar features, namely, a subacute dermatitis with variable pigment incontinence. Immunohistochemical labeling revealed a preponderance of T lymphocytes. Pigmenting pityriasis alba seems to be a variant of classic pityriasis alba showing a strong association with dermatophyte infection, especially tinea capitis. It may be related to lichenoid melanodermatitis. PMID- 8493159 TI - Bilateral skin dimples on the shoulders. AB - Cutaneous depressions, commonly known as dimples, are uncommon in locations other than the face. An infant had deep dimple-like depressions near the acromion bilaterally. This most likely represents benign autosomal acromial dimples, a rarely reported autosomal dominant condition. Other causes of dimples include a variety of congenital malformation syndromes, and infectious, metabolic, and traumatic etiologies. Awareness of the etiology and significance of skin dimples is helpful to the clinician when confronted with this unusual finding. PMID- 8493160 TI - Juvenile pseudoxanthoma elasticum: recognition and management. AB - An 8-year-old girl had pseudoxanthoma elasticum (PXE) with the characteristic skin and ocular findings. She had no associated systemic symptoms and no family history of PXE. The disease was most likely inherited in an autosomal recessive fashion. It is reviewed with regard to etiology, inheritance, diagnosis, and, particularly, management. PMID- 8493161 TI - Familial occurrence of isolated accessory tragi. AB - Three sibs were affected by numerous accessory tragi. On clinical examination, no other associated developmental defects, such as the Goldenhar syndrome, were detected. PMID- 8493162 TI - Acute alopecia: clue to thallium toxicity. AB - The combination of rapid, diffuse alopecia, and neurologic and gastrointestinal disturbance is pathognomonic for thallium toxicity. The hair mount, showing a tapered or bayonet anagen hair with black pigmentation at the base, may be highly diagnostic before the onset of alopecia. We saw a 10-year-old boy who suffered from thallium poisoning. PMID- 8493163 TI - Alopecia in children after cardiac surgery. AB - Postoperative alopecia is an uncommon complication of surgery and is reported mainly in adults who undergo prolonged anesthesia. The disorder occurred in three infants after cardiac surgery. It is easily prevented by frequently changing the position of the head during surgery and the recovery period. PMID- 8493164 TI - Nonprogressive scrotal hair growth in two infants. AB - Two infant boys developed scrotal hairs within the first three months of life. There was no other clinical or biochemical evidence of excessive androgen production, and no further progression of hair growth. PMID- 8493165 TI - Lichen planus limited to the nails in childhood: case report and literature review. AB - Although nail abnormalities have been reported to occur in 1% to 10% of patients with lichen planus, in children with lichen planus they are rarely mentioned in the literature. An 11-year-old boy had a two-month history of nail dystrophy affecting all the fingernails and the great toenails. The nail plates showed longitudinal ridging and thinning as well as onycholysis and distal splitting. There were no cutaneous or mucous membrane abnormalities. A nail biopsy specimen showed hyperkeratosis, hypergranulosis, and acanthosis in the ventral portion of the proximal nail fold and in the nail matrix. A band-like lymphocytic infiltrate was present in the superficial dermis, and the basal layer showed vacuolar alterations. A diagnosis of lichen planus was made. Treatment was intramuscular triamcinolone 20 mg once a month for six months. Since 1969 only 13 proved pediatric cases of lichen planus limited to the nails have been reported, including two children with 20-nail dystrophy and four with idiopathic atrophy of the nails. PMID- 8493166 TI - Congenital dermatofibrosarcoma protuberans. AB - Congenital dermatofibrosarcoma protuberans occurred in a 16-year-old girl. The lesion was a hard cutaneous plaque on the abdomen. It was present at birth and slowly enlarged during the patient's lifetime. Histologic examination was essential to establish the diagnosis and to differentiate it from other congenital fibrohistiocytic proliferations. PMID- 8493167 TI - Segmental neurofibromatosis with only macular lesions. AB - A 16-year-old girl had a three-year history of many cafe au lait spots and freckles in a dermatomal distribution. The diagnosis of segmental neurofibromatosis (NF-5) was made on the basis of the clinical features, distribution of the lesions, and absence of systemic involvement. Only a few cases in the literature describe NF-5 with only macular lesions. An accurate clinical examination is important to identify this unusual presentation. PMID- 8493168 TI - Persistent annular erythema of infancy. AB - Annular erythema of infancy is an uncommon, nonpruritic, figurate erythema that begins in the first year of life. Biopsy specimens reveal a perivascular and interstitial lymphocytic infiltrate with numerous eosinophils. The cause of the disorder is unknown, but a hypersensitivity response to unrecognized antigens is suspected. The disorder is self-limited, but may last for many months. In our patient the eruption continued 19 months after its onset. PMID- 8493169 TI - Musculoaponeurotic fibromatosis (extraabdominal desmoid tumor) in a child with idiopathic multicentric osteolysis. AB - The fibromatoses are a group of benign proliferations of fibrous tissue with clinical behavior ranging from that of truly malignant tumors to that of benign reactive fibrous proliferations. Some of the superficial fibromatoses are fairly common, but the deep ones, also known as desmoid tumors or musculoaponeurotic fibromatoses, are rare. Idiopathic multicentric osteolysis is a rare skeletal disorder of childhood that causes progressive destruction of bones and renal failure. We recently saw a young girl with both extraabdominal musculoaponeurotic fibromatosis and idiopathic multicentric osteolysis. The classification, diagnosis, and treatment of the deep fibromatoses are reviewed, and the possible association between the minor bone changes occasionally reported in musculoaponeurotic fibromatosis and idiopathic multicentric osteolysis is discussed. PMID- 8493170 TI - Rapp-Hodgkin syndrome with pili canaliculi. AB - A 20-year-old woman and her 12-year-old brother had hypohidrotic ectodermal dysplasia, cleft lip and palate, midfacial hypoplasia with narrow nose from the nasal bridge to the tip, narrow dysplastic nails, and conical teeth and hypodontia, and hypospadias and hypoplastic uvula in the boy. The woman had major underdevelopment of intellectual capacity. The most important hair anomalies in both siblings were sparse eyebrows, pili torti, and pili canaliculi. Some of the pili canaliculi had two canals (pili bicanaliculi), and the cross section for scanning electron microscopy had a quadrangular aspect. This is the seventh family reported with Rapp-Hodgkin ectodermal dysplasia. PMID- 8493171 TI - Neonatal group B streptococcal cellulitis-adenitis. AB - A 38-day-old prematurely born infant developed rapidly progressive facial cellulitis in association with ipsilateral submandibular lymphadenopathy and pulmonary consolidation. Group B streptococci (GBS) were isolated from blood, endotracheal, and lesion cultures. Prompt recognition of GBS cellulitis-adenitis and institution of parenteral, synergistic antibiotic therapy are important. PMID- 8493172 TI - Cutis marmorata telangiectatica congenita: long-term follow-up, review of the literature, and report of a case in conjunction with congenital hypothyroidism. AB - Cutis marmorata telangiectatica congenita is an uncommon, generally congenital, cutaneous condition. The major skin findings are persistent, fixed cutis marmorata, telangiectasia, and phlebectasia; often, there is associated skin atrophy and ulceration as well. Significantly, two-thirds of patients have other congenital anomalies, although often minor ones. We report a series of eight children with cutis marmorata telangiectatica congenita, including one with associated congenital hypothyroidism, a relationship that has never before been noted. PMID- 8493173 TI - Juvenile xanthogranuloma with central nervous system involvement. AB - An 18-year-old man has been followed in our department since age 10 years when he began to develop numerous yellow, papular lesions on the scalp, face, neck, trunk, and upper extremities. The lesions enlarged slowly to form yellow-brown nodules measuring up to 6 cm. During this period five of the nodules and two small papules were excised. Histopathology was consistent with juvenile xanthogranuloma (JXG). Recently, the patient complained of significant loss of memory, and a computed tomography scan was performed showing several cerebral and cerebellar lesions. The cutaneous lesions in our patient were almost identical to those described elsewhere as being characteristic of progressive nodular histiocytoma. The many clinical and histopathologic similarities between lesions of progressive nodular histiocytoma and JXG suggest that they may represent a continuum rather than two distinct disease processes. Given the fact that there are no histopathologic differences with JXG, as well as the wide range of clinical lesions that JXG may adopt, there is no reason to separate the entities. Although JXG lesions are usually believed to be benign and self-healing, large nodular forms can be associated with visceral lesions. Only four previous cases of cutaneous JXG with central nervous system involvement were found in a review of the literature. PMID- 8493174 TI - Dermoid cyst connected with the lacrimal canaliculum. AB - An infant had a 3 x 1.5-cm congenital, slow-growing, lobulated tumor below the right inferior eyelid. The mass transilluminated, and needle aspiration yielded tears. Dacryocystography showed a large cystic area connected with the lower lacrimal canaliculum. Histologically, the tumor proved to be a dermoid cyst. This association has not been reported previously. Surgical excision and suture of the pedicule resulted in permanent cure. PMID- 8493175 TI - Supraumbilical midabdominal raphe, sternal atresia, and hemangioma in an infant: response of hemangioma to laser and interferon alfa-2a. AB - We cared for an infant girl with the clinical constellation of supraumbilical midabdominal raphe, sternal atresia, and cutaneous facial and upper trunk hemangioma. This is the first report of this clinical association in the dermatologic literature. The vascular component of the disorder responded to flashlamp-pumped pulsed dye laser therapy and to systemic interferon alfa-2a (Roferon-A). PMID- 8493176 TI - Failure of the flashlamp-pumped pulsed dye laser to prevent progression to deep hemangioma. AB - Hemangiomas are common vascular lesions in children. The flashlamp-pumped pulsed dye laser has shown excellent results in the treatment of port-wine stains and, more recently, superficial (capillary) hemangiomas. Four patients with clinically evident superficial hemangiomas illustrate the point that early treatment with this laser may not preclude growth of a deeper component of the lesions. PMID- 8493177 TI - The impact of ozone depletion on the skin. PMID- 8493178 TI - On the treatment of hemangiomas. PMID- 8493179 TI - What syndrome is this? Buschke-Ollendorff syndrome. PMID- 8493180 TI - Solitary congenital nodule on the ear of an infant. PMID- 8493181 TI - Hearing disorders. PMID- 8493182 TI - Disordered control of breathing in infants and children. PMID- 8493183 TI - Medical record review. Same patient, same problem, two different stories: the value of a prospective diary in assessing chronic abdominal pain. PMID- 8493184 TI - Fluids and electrolytes: physiology. PMID- 8493185 TI - Adult respiratory distress syndrome. PMID- 8493186 TI - Hypertension in childhood and adolescence. PMID- 8493187 TI - Sexually transmitted diseases in adolescents. PMID- 8493188 TI - Index of suspicion. Case 1. Submucous cleft palate. PMID- 8493189 TI - Index of suspicion. Case 2. Hemorrhagic disease of the newborn. PMID- 8493190 TI - Index of suspicion. Case 3. Kernicterus in a baby girl homozygous for glucose-6 phosphate dehydrogenase deficiency. PMID- 8493191 TI - A clinical overview of systemic lupus erythematosus in childhood. PMID- 8493192 TI - Enterococcal infections. AB - An 8-year-old male suffered multiple trauma in a motor vehicle accident. He has been in intensive care and has multiple intravascular catheters and an indwelling Foley catheter. He has received 6 days of a third-generation cephalosporin antibiotic. On day 7, he develops a spiking temperature but no other evidence of infection. However, both of the two blood cultures and a urine culture grow out enterococcus. PMID- 8493193 TI - What to look for after you say 'open wide'. A guide to examination of the oral cavity. AB - Abnormal conditions of the oral cavity can have a significant impact on overall health, yet during many ostensibly complete physical examinations, the area is given only a perfunctory glance. Drs Thomas and Bender present guidelines for systematic, comprehensive evaluation of the oral cavity and provide case reports and figures to illustrate typical important findings. PMID- 8493194 TI - Right ventricular infarction. Aids to recognition. AB - Right ventricular infarction is often associated with myocardial infarction located in the inferior or posterior left ventricular wall. It should be suspected if a patient has distended neck veins with Kussmaul's sign, ST-segment elevation in the V4R precordial lead, possible heart block, and extreme sensitivity to preload reducers such as nitroglycerin and diuretics (administration of which may lead to hypotension). Measures such as administration of fluid (with Swan-Ganz monitoring), inotropic support with dobutamine (Dobutrex), and atrioventricular sequential pacing may be of benefit in hypotensive patients. Mortality can be significant, especially when there is hemodynamic compromise; however, reperfusion as a result of thrombolytic therapy or angioplasty may have a salutary effect. Early investigations imply that long lasting benefit is obtained from opening an infarct-related artery. PMID- 8493196 TI - 'Death by Varuba!' Congressman arrogantly tells doctors. PMID- 8493195 TI - Drug treatment of arthritis. Update on conventional and less conventional methods. AB - Nonsteroidal anti-inflammatory drugs comprise an important class of medications that reduce the signs and symptoms of osteoarthritis and rheumatoid arthritis. They bring relief to millions of people but do not eliminate underlying disease. Disease-modifying antirheumatic drugs also bring relief, but these drugs are often ineffective and not well tolerated. Failure to provide long-term benefits combined with the high toxicity of most of the disease-modifying agents has prompted a search for more effective treatments. New methods using modern technologies have generated much enthusiasm and hold promise for the future. In the meantime, administration of nonsteroidal anti-inflammatory drugs and judicious use of disease-modifying agents remain the cornerstone of therapy for arthritis. PMID- 8493197 TI - Bacterial pneumonia. S pneumoniae and H influenzae are the villains. AB - Bacterial pneumonia isn't what it used to be. The most common causes, Streptococcus pneumoniae and Haemophilus influenzae, are developing strains that are resistant to powerful antibiotics: How do you choose a therapeutic agent? New organisms are being discovered to be culprits in this disease: How do you keep track of them? New drugs are being developed every day: How does that help if initial treatment is almost always empirical? Dr Wisinger identifies the problems and offers advice. PMID- 8493198 TI - Atypical pneumonias. Clinical and extrapulmonary features of Chlamydia, Mycoplasma, and Legionella infections. AB - Pneumonias caused by atypical organisms usually have extra-pulmonary features. Chlamydial pneumonia often starts with hoarseness and fever, and respiratory tract symptoms may not appear for days. Mycoplasmal pneumonia may manifest with ear pain and a nonproductive cough. Legionnaires' disease presents with high fevers and central nervous system and gastrointestinal abnormalities. Diagnosis of chlamydial infection is accomplished with serologic testing. Patients are unresponsive to erythromycin treatment and should be started on empirical doxycycline (Doryx, Vibramycin) therapy. The presence of cold agglutinins in the appropriate clinical setting permits a presumptive diagnosis of mycoplasmal infection. Clinical diagnosis of Legionella pneumonia may be made in patients with pneumonia who also have relative bradycardia with elevated serum transaminases or hypophosphatemia with gastrointestinal or central nervous system symptoms. Erythromycin is the mainstay of treatment of legionnaires' disease, but treatment failures have been reported. Doxycycline is less expensive, has a better safety profile, and is better tolerated than erythromycin. PMID- 8493199 TI - [Ego development in the transition from adolescence to young adulthood: an empirical comparative study of psychiatric patients and healthy control probands]. AB - The model of ego development by Loevinger describes an epigenetic series of successive stages comprising increasingly complex styles of impulse control, interpersonal relationships, moral and cognitive reasoning. This model offers an opportunity to explore the structural premises young adults rely on solving their developmental tasks. Controls compared to patients show a significantly superior intrapsychic coping, awareness of social rules and knowledge of interpersonal relations. Except non-psychotic patients who seem to dispose of slightly more mature ego capacities than psychotic patients there prevails a dominant psychosocial immaturity among all patient subgroups however. The results are discussed in relation to psychopathological syndromes, the actual status of a psychiatric illness, and differently favourable patterns of psychosocial adaptation defined by results in the Offer-Self-Image-Questionnaire. PMID- 8493200 TI - [Rules of specialty skills in psychosocial counseling of children, adolescence and parents]. AB - This article is a revised version of a short expert opinion of the Ministry of Work, Health and Social Matters of the state of North Rhine-Westphalia (West Germany) dealing with the rules of expert skills in educational counselling. After the attempt of clarifying terms (consultation, therapy, medicine) the processes of consultation and treatment are described in general as influencing in a communicative way, whereby common qualitative characteristics are pointed out. The author also goes into taking ethical principles into consideration, possibilities of preventive effectiveness and consequences for education and further training of experts working in educational counselling facilities. PMID- 8493201 TI - [The 'third relationship': triangulating functions in analytic child and adolescent psychotherapy]. AB - Whereas the theoretic concept of "triangulating" up to now was used to explain development processes from dyadic to three-person-relationships in the course of releasing and individuation (Abelin, 1971; Rotmann, 1978) or to illuminate misdirected developments and therefore to gain a better understanding of the patient in clinical work (i.e. Ermann, 1985; Rohde-Dachser, 1987; Hirsch, 1988) in this article the author describes the practical therapeutic relevance in analytic child and adolescent psychotherapy with the use of a case example. Analogous to the significance of the father for individuation and releasing in the early development of the child the author shows the actual "triangulating" action of the therapist in the depth psychological treatment of a 14 year old youth and in the accompanying psychotherapy of the parents. In closing the conditions which allow for change within all participants and lead to restructuring the relationships are discussed. PMID- 8493202 TI - [Sexually aggressive acts of an adolescent with Klinefelter syndrome]. AB - Using the case of an average gifted 15 years old youth with Klinefelter-syndrome (ks), who acted in a sexually aggressive manner, first the characteristics of this syndrome are described. In the following personality development and family background are compared to three hitherto published case examples of youths with ks or similar symptomatics on the one hand, and forty other sexually aggressive acting youths without ks on the other hand. In closing the possible significance of a treatment with a testosterone substitute is discussed. PMID- 8493203 TI - [Evaluation of risk of arrhythmia after myocardial infarction]. PMID- 8493204 TI - [Frequency of hypothyroidism in a population of hyperlipidemic subjects]. AB - Hypothyroidism is a classical cause of hypercholesterolaemia. As we sometimes met patients with hyperlipidaemia whose thyroid state was unknown, we carried out a prospective study aimed at evaluating the frequency of hypothyroidism in a population of 1210 hyperlipidemic patients who were referred to our out-patient clinic at the La Pitie Hospital, Paris, for metabolic and cardiovascular assessment. The proportion of subjects with high thyroid-stimulating hormone (TSH) levels was 12, 56 percent, which is distinctly higher than the figures reported in previous studies in patients who were not selected for lipid abnormalities. Among those with high TSH levels, 16 had overt hypothyroidism with a low free T4 level. Analysis of lipid parameters showed that hypertriglycidaemia was frequent and did not confirm the hyperHDLaemia classically observed in hypothyroidic populations. We conclude that screening for hypothyroidism by measuring TSH values is of particular importance in patients with hyperlipidaemia, especially in the group of women over 50 years of age. PMID- 8493205 TI - [Fuel tanks of motorcycles. Role in severe trauma of the pelvis]. AB - Between 1985 and June 1992, 8 subjects who sustained severe pelvic lesions as a result of motor cycle accidents were admitted and treated in our department. In 5 of these 8 patients the fuel tank of the motor cycle was one of the wounding agents. All 5 patients had unstable pelvic lesions. In addition, 4 had a subperitoneal haematoma which required multiple transfusions; 4 had perineal and/or genital lesions, and 1 had a ruptured membranous urethra. A national epidemiological study would be useful to evaluate the frequency of these particular injuries and draw lessons that would lead to better safety of motor cyclists. PMID- 8493206 TI - [Cystic lymphangioma of the adrenal gland. Three misleading cases]. AB - Three cases of adrenal cystic lymphangioma are reported. In 1 patient the lesion was complicated by intracystic haemorrhage. The remaining 2 patients had a hepatic lesion which was treated in the same surgical operation as the adrenal cyst. Ultrasonography and computerized tomography play a major role in the exploration of these cysts. Their unexpected discovery has become more frequent since these methods have multiplied, and this raises therapeutic problems. The nature of adrenal cysts is determined at histology. In asymptomatic cysts percutaneous needle aspiration can only have an indicative value. PMID- 8493207 TI - [Photoimmunology of melanoma]. AB - Several epidemiological studies suggest that exposure to ultraviolet radiation and immunological responsiveness of the host contribute to the etiology of melanoma. In addition, a growing experimental evidence indicates a stimulant effect of ultraviolet radiation and a high immunogenicity of melanocytic tumors. These findings lead to the hypothesis of an ultraviolet-induced alteration of the immune response that decreases the host-resistance to melanoma antigens. PMID- 8493208 TI - [Blackwater fever after ingestion of mefloquine. Three cases]. PMID- 8493209 TI - [Leukopenia and thrombocytopenia in Still's disease]. PMID- 8493210 TI - [Preoperative ultrasonographic diagnosis of a purulent cyst of the urachus, responsible for peritonitis]. PMID- 8493211 TI - [Chemical meningitis simulating infectious meningitis after intradural injection of corticosteroids]. PMID- 8493212 TI - [Accidental overdosage of cisplatin. Favourable outcome after early treatment]. PMID- 8493213 TI - [Langerhans-cell histiocytosis in adults]. PMID- 8493214 TI - [Treatment of cancers of the ovary. Phase II trial of increase of the dose of cisplatin]. AB - Between March 1985 and December 1987, 34 women who had advanced adenocarcinoma of the ovary with macroscopic residual disease entered in a phase II trial of chemotherapy. Treatment consisted of a 3-month induction with monthly ifosfamide combined with 5-fluorouracil and high-dose cisplatin, and a maintenance treatment with ifosfamide, 5-fluorouracil, cisplatin and hexamethylmelamine in monthly cycles. At the end of the treatment patients with complete remission were evaluated by surgery. Neurotoxicity was a limiting factor, and treatment had to be prematurely withdrawn in 10 patients. The above treatment was found to be effective with a 94 percent objective response rate, a 54-month median survival and a 51-month median relapse-free survival. Because of the neurotoxicity, a shorter therapy and the use of neuroprotective agents may be envisaged. PMID- 8493215 TI - [Hematopoietic growth factor (GM-CSF) after autologous bone marrow transplantation. A randomized, double-blind, multicenter study in 91 cases of non Hodgkin's malignant lymphomas]. AB - To a great extent, the risks of autologous bone marrow transplantation are related to neutropenia. Although the efficacy of the recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) on neutrophil recovery has appeared in numerous open trials, only a few randomized studies have hitherto been published. Ninety-one patients with non-Hodgkin's malignant lymphoma treated with ablative chemotherapy followed by purged or unpurged bone marrow transplantation were entered in a placebo-controlled, double-blind randomized study; 44 patients received GM-CSF (E. coli) in doses of 250 micrograms/m2/day, and 47 received a placebo. Treatment was administered daily as continuous infusion started on the day of transplantation and pursued until the absolute number of neutrophils reached 0.5 x 10(9)/l during 7 days or, if this failed, during 30 days. The median time of neutrophil recovery was 14 days in patients on rhu GM-CSF and 21 days in patients on placebo (P < 0.0001). Patients who received a mafosfamide-purged bone marrow also had a rapid neutrophil recovery (median: 16 days versus 20.5 days; P = 0.013). The stay in hospital was shorter in the rhu GM-CSF group (median: 23 days versus 28 days; P < 0.05). No significant difference in the number of days with fever, infections, antibiotics administered and overall survival was detected between the two groups. The main toxicity ascribable to rhu GM-CSF was a capillary leakage syndrome found in 3 patients. Thus, after purged or unpurged autologous bone marrow transplantation rhu GM-CSF significantly reduces the duration of both neutropenia and hospital stay. PMID- 8493216 TI - [Mitochondrial ocular myopathy sensitive to anticholinesterase agents]. PMID- 8493217 TI - [Postoperative brain abscess caused by Salmonella enteritidis]. PMID- 8493218 TI - [Gaseous effusion opposite the hepatic area. A rare mode of revelation of liver abscess]. PMID- 8493219 TI - [Unpackaging drugs: a necessity for elderly people. 3 cases of esophageal impaction]. PMID- 8493220 TI - [Contribution of thoracic magnetic resonance imaging to the diagnosis of pulmonary infarction]. PMID- 8493221 TI - [Diagnosis of salmonelloses by titration of anti-lipopolysaccharide antibodies using an ELISA method]. PMID- 8493222 TI - [High-degree atrioventricular block revealing the first case of Lyme's disease in the Alpes-Maritimes department]. PMID- 8493223 TI - [Hypoglycemia induced by dextropropoxyphene: an emergency in drug addicts]. PMID- 8493224 TI - [Emergency surgery]. PMID- 8493225 TI - [C-reactive protein in bacterial meningitis in adults]. AB - In order to assess the benefits of serial assays of C-reactive protein in the course of bacterial meningitis in adults, daily blood samples were taken for CRP measurement during 10 days in 21 consecutive patients (mean age: 24 +/- 8 years) hospitalized for bacterial meningitis principally due to Neisseria meningitidis (n = 15). The highest CRP level (178 +/- 38 mg/l) was present on admission, followed by a regular decrease occurring in uncomplicated meningitis until normal level was achieved on day 9. The CRP kinetics was not influenced by the type of causative micro-organism. This study shows that CRP kinetics in adults is similar to that reported in children. The benefit of CRP assays in optimizing the duration of antibiotic treatment of meningitis needs to be more carefully assessed. PMID- 8493226 TI - [Food-related fungal infection risk in agranulocytosis. Mycological control of 273 food items offered to patients hospitalized in sterile units]. AB - In sterile hospital units filamentous fungal infections are an unacceptable risk in patients with prolonged agranulocytosis. The occurrence of 3 successive cases in the Sterile unit of University Hospital of Grenoble prompted us to investigate in all elements of sterile unit, and notably food-processing. Two cooked rice dishes given to these patients were found to contain a substantial amount of Aspergillus fumigatus and were probably responsible for these infections. A more detailed study was carried out to evaluate the degree of food contamination by fungi in sterile unit. The study included 97 cooked dishes which had been sterilized in a 250 degrees oven for 40 minutes and 176 industrially packed foods delivered in single packs (e.g. milk and its derivatives, sweets and drinks). Each foodstuff was mycologically examined 3 to 5 times in different packs according to a procedure used in food analysis laboratories and raised to the standards of mycological examination. In this way, a 3-monthly food testing protocol in sterile unit could be set up. This protocol has a dual purpose: regular checking of the cooked dishes chain and maximum diversification of the dishes. PMID- 8493227 TI - [Extrapulmonary and disseminated pneumocystosis in HIV infection]. AB - Three cases of extrapulmonary disseminated Pneumocystis carinii infection are reported. All 3 patients had HIV infection with less than 50 CD4 lymphocytes per cubic millimeter and were having aerosols of pentamidine as prophylactic treatment of pneumocystosis. P. carinii may invade numerous organs and in particular the liver, spleen and bone marrow. Extrapulmonary lesions, often pan symptomatic, are to be feared in deeply immunodepressed patients receiving prophylactic aerosols of pentamidine. Infection of the choroid can be detected by systematic ophthalmoscopy. An early diagnosis raises hopes of a good, if temporary, response to treatment. PMID- 8493228 TI - [Autonomic diabetic neuropathy]. AB - Diabetic autonomic neuropathy is rarely symptomatic but very frequent at a subclinical stage. Symptoms may be gastrointestinal, urinary, genital or cardiac. Sudoral, vasomotor or pupillary symptoms may also occur. Standardized cardiovascular tests are used to investigate parasympathetic and sympathetic nervous control. Because of their easy feasibility and good reproducibility they might be performed in the largest part of the diabetic population. These tests also strongly suggest that cardiac autonomic neuropathy is of poor prognosis, even when it is subclinical. Most treatments are symptomatic, but optimized diabetes control and administration of aldose reductase inhibitors are rational therapeutic measures, although their long-term effectiveness remains to be demonstrated. PMID- 8493229 TI - [Immediate allergic reaction after ingestion of a dietary bar containing psyllium]. PMID- 8493230 TI - [Right adrenalectomy by celioscopy for primary aldosteronism]. PMID- 8493231 TI - [Influenza following heart transplantation in a patient, an unusual cause of viral pneumonia]. PMID- 8493232 TI - [Regressive trigeminal neuropathy under dapsone in temporal arteritis]. PMID- 8493233 TI - [Painful legs and involuntary movements of the toes. Indirect therapeutic role of adenosine]. PMID- 8493234 TI - [Vasculitis with mixed cryoglobulin in human parvovirus B19 infection]. PMID- 8493235 TI - [Double Listeria monocytogenes and Leptospira infection]. PMID- 8493236 TI - [Severe hyponatremia induced by meprazole]. PMID- 8493237 TI - [Indication for liver transplantation in Amanita phalloides poisoning]. PMID- 8493238 TI - [Treatment of status asthmaticus with halothane]. PMID- 8493239 TI - Production of interferon by Theileria annulata- and T. parva-infected bovine lymphoid cell lines. AB - Theileria annulata and T. parva-infected lymphoblastoid cells were examined for their capacity to produce interferon (IFN). Supernatants of such cells were tested in biological assay for their antiviral activity. Only T. parva-infected cells of T-cell origin were capable of producing IFN-gamma. Supernatants of some but not all T. annulata-infected cells showed also antiviral activity, which was greatly reduced after exposure to a pH of 2. Northern-blot analysis of the cells using an IFN-gamma cDNA probe confirmed the results obtained for T. parva infected cells in a biological assay. No IFN-gamma mRNA was detected in T. annulata-infected cells. The importance of IFN for the pathogenesis of theileriosis is discussed. PMID- 8493240 TI - Efficacy of abamectin injection against Dermatobia hominis in cattle. AB - The efficacy of abamectin 1%, when injected subcutaneously in cattle at a dose of 200 micrograms/kg body weight, against the larval stages (grubs) of the fly Dermatobia hominis was evaluated in two trials in endemic areas of Brazil and Argentina. Eighteen Holstein x Brahman castrated males and 16 Brahman-cross with natural infestations were used. Larvae were counted by instar in situ on both sides of each animal before treatment, and were expressed, identified as to stage and classified as live or dead 10 days after treatment. Further larval counts were made periodically until day 79 to evaluate the degree of reinfestation and the stage of larval development. Reinfestation was first detected in the abamectin-treated cattle on day 44. Live larvae were found on 6-8 (Argentina) and on all (Brazil) controls at each post-treatment examination. The difference in numbers of live larvae between treatment groups was statistically significant (P < 0.05) at all post-treatment examinations. These data show that abamectin at a dose of 200 micrograms/kg body weight is highly effective in the treatment and control of established parasitic stages of D. hominis in cattle. No adverse reactions were observed in any of the treated animals. PMID- 8493241 TI - Eimeria sp. from the rabbit (Oryctolagus cuniculus): pathogenicity and immunogenicity of Eimeria intestinalis. AB - The pathogenicity and immunogenicity of Eimeria intestinalis was evaluated in SPF rabbits. The animals were given immunizing doses of 6, 6 x 10(2), 6 x 10(3), and 6 x 10(4) sporulated oocysts and were challenged with 3 x 10(3) oocysts. The criteria analysed were the daily weight gain and the oocyst output. This study showed that E. intestinalis had strong immunogenicity, as the inoculation of 6 oocysts was sufficient to minimize the clinical expression of the disease following the challenge and to reduce the oocyst output by about 60%. The immunity towards the excretion of oocysts and the illness was absolute in animals inoculated with 600 or more oocysts. Moreover, this protection seemed to be efficient at least 8 weeks after the challenge. The present results also confirm the pathogenicity of E. intestinalis, although the occurrence of diarrhoea may be irregular, and emphasize the fact that the capacity of this Eimeria for multiplication is not a criterion for clinical diagnosis of the disease. PMID- 8493242 TI - Some characteristics of ovine lymphoid cells infected in vivo by Theileria hirci. AB - A panel of monoclonal antibodies reacting with different subsets of sheep lymphocytes plus a polyclonal rabbit anti-sheep Ig antiserum were used to characterize three Theileria hirci-infected lymphoid cell lines that had been infected and transformed in vivo. In parallel, peripheral blood mononuclear cells of Swedish Landrace sheep were exposed to the same antibodies. Whereas the values obtained for healthy Swedish Landrace sheep peripheral mononuclear cells fell within the range previously described for the sheep, T. hirci-infected lymphoid cells reacted only with monoclonal antibodies specific to major histocompatibility (MHC) class I and class II antigens and to leukocyte common antigen (LCA). The results are discussed in the light of the present knowledge on characteristics of bovine lymphoid cells infected and transformed in vivo and in vitro by the related parasites T. parva and T. annulata. Assumedly, the characteristics of ovine lymphoid cells infected with T. hirci bear likeness to those of bovine cells infected with T. annulata. PMID- 8493243 TI - Entamoeba histolytica cysts with a defective wall formed under axenic conditions. AB - Axenic HK9 Entamoeba histolytica strain amoebae, maintained in PEHS medium, displayed several cystic characteristics that involve an active process of cystic wall formation, cellular volume and density diminution, and one or two nuclear divisions. The differentiation process was asynchronic, beginning after the logarithmic growth phase. The axenic cysts, which were maintained in a 50 mOsm/kg medium at 4 degrees C for 72 h, produced growing trophozoites within 1-7 days of incubation at 36 degrees C in fresh medium. Negative results were obtained with trophozoites submitted to the above treatment, and with axenic cysts maintained in double-distilled water at 4 degrees C for 24 h, or in 0.1% sarkosyl, for 10 min at room temperature instead of 55 mosmol/kg medium. Thus, the HK9 E. histolytica strain, cultured in PEHPS, produced under axenic conditions a small proportion of mature, metabolically active cysts, but with an immature or abnormal wall. PMID- 8493244 TI - Ultrastructural study of the spermatogenesis and mature spermatozoa of Dicrocoelium dendriticum (Plathelminthes, Digenea). AB - The spermatogenesis and spermatozoon of Dicrocoelium dendriticum were studied by transmission electron microscopy. Peripheric accessory cells project between germ cells. Each spermatogonium gives rise to 32 spermatozoa. The stages in spermiogenesis include development of the zone of differentiation, appearance of the intercentriolar body flanked by two centrioles from each of which a free axoneme and a striated rootlet grow, outgrowth of the differentiation zone to form the median cytoplasmic process and migration of the nucleus and mitochondria into it, and rotation of the flagella and subsequent proximodistal fusion of the three projections to form a monopartite spermatozoon. The spermatozoon possess two incorporated axonemes with the "9 + 1" pattern typical of those in trepaxonematid plathelminths. beta-Glycogen particles accumulate in the spermatozoa after they have separated from the cytophore as revealed by Thiery's method. This study confirms in a further family, Dicrocoeliidae, the constant pattern of spermiogenesis and spermatozoon structure in Digenea. PMID- 8493245 TI - Ultrastructural observations on the nervous system and the sensory organs of the infective stage (L3) of Onchocerca volvulus (Nematoda: Filarioidea). AB - A detailed morphological investigation of the sensory organs and the nervous system of the third juvenile stage of Onchocerca volvulus was performed at the ultrastructural level. A complex system of different receptor cells is found at the anterior and posterior end of this developmental stage. The eight papillae are arranged in two concentric circles consisting of two types of morphologically different receptors. Accessory nerve processes end free in the tip of the head. The paired amphids contain nine dendritic processes and accessory axons are seen in the surrounding cells. The basic structure of the amphids and of the circumoesophageal nerve ring is similar to that of other filarial nematodes. Two presumably neurosecretory cells are associated with the nerve ring. The reticular cytoplasm of these cells merges with the rough-surfaced endoplasmic reticulum of the lateral hypodermal chord. The paired phasmids at the posterior end of the developmental stages consist of single modified cilia that are embedded in an electron-dense mass. The receptor cell has access to the outside by a channel ending with a cuticular pore. PMID- 8493246 TI - Babesia bovis: in vitro phagocytosis promoted by immune serum and by antibodies produced against protective antigens. AB - The in vitro phagocytosis of both Babesia bovis-infected red cells and of parasites exposed by lysis of infected red blood cells is demonstrated in a phagocytic mouse model. Twenty-four B. bovis immune sera were tested alone or as a pool as were antibodies (DS antibodies) raised against a B. bovis protective fraction, prepared by dextran sulfate precipitation. All the immune sera failed to promote significant levels of phagocytosis, whereas the other antibodies (DS antibodies) consistently induced phagocytosis of infected cells in all the experiments carried out. This study shows that antibody specificity is critical to the opsonization of infected red cells and parasites during in vitro phagocytosis and suggests that phagocytosis is one of the mechanisms in the in vivo immune response against Babesia species. PMID- 8493247 TI - Kinetic model of parasite development and of the host microelement content under combined drug treatment. AB - The content of nine microelements has been investigated in a parasite-host system by nondestructive neutron activation analysis. A mathematical model has been proposed for the development of Ascaridia galli in the "Leghorn" chicks intestines and for the microelement content dynamics under combined treatment with antiparasite agent and microelements. An analytical solution of the system of nonlinear differential equations has been obtained for the case of simple invasion. The model explains well the experimentally observed process of the change in the microelement content. The recovery constant has been introduced for the damaged by the helminthosis tissue and its value has been determined. PMID- 8493248 TI - Response to repeated inoculations with Ascaris suum eggs in pigs during the fattening period. II. Specific IgA, IgG, and IgM antibodies determined by enzyme linked immunosorbent assay. AB - Experimental trickle inoculations of pigs with low doses (2 x 25 eggs/week) and high doses (2 x 500 eggs/week) of Ascaris suum were followed by enzyme-linked immunosorbent assay (ELISA) during a 14-week period. Three antigens were employed for coating: hatching fluid of embryonated eggs, excretory/secretory antigens from in vitro-cultivated infective larvae (L2/L3-ES), and adult body fluid. Seroconversion times (week 2 for the high-dose group and week 4 for the low-dose group) were essentially identical for the three antigens. The assay employing L2/L3-ES, however, produced significantly higher readings. Specific serum antibody in the IgA and IgG classes showed very similar time courses in both groups. A weak and transient, specific IgM response was recorded in the high-dose group. Mean ELISA responses to L2/L3-ES did not differ significantly between the groups at the termination of the experiment. Specific antibody correlated weakly with the number of liver milk spots recorded at slaughter. PMID- 8493249 TI - Ultrastructure and microanalyses of the calcareous corpuscles of the protoscoleces of Echinococcus granulosus. AB - The calcareous corpuscles of the protoscolex stage of Echinococcus granulosus are irregularly spherical or ovoid in shape and have a diameter ranging between 2 and 16 microns. The central region of immature corpuscles is composed of an electron lucent matrix containing granular deposits and, in more mature corpuscles, paired membrane lamellae. Energy-dispersive X-ray microanalysis of sectioned immature corpuscles demonstrated calcium, magnesium and phosphorus, whilst a quantitative analysis indicated the presence of calcium and magnesium at 142.7 and 41.3 mg/g dry weight, respectively, and inorganic phosphate at 18.0 mg/g. Assuming that the anion is predominantly carbonate, the molar ratio of Ca:Mg:HPO4(2-):CO3(2-) is 1:0.48:0.08:1.41. X-ray diffraction patterns obtained from preparations of whole corpuscles indicated a poorly crystalline material including the mineral calcite. X-ray absorption near-edge spectra of corpuscles, taken over the phosphorus K edge, resembled those of brushite (CaHPO4.2H2O) and suggest that the phosphate, within the corpuscles, is present in an amorphous, hydrated form that could be readily solubilised and mobilised for the metabolic processes of the organism. PMID- 8493250 TI - Studies on the host specificity of the medicinal blood leech Hirudo medicinalis L. AB - For the identification of host species of blood-sucking parasites, the suitability of disc-electrophoresis of the stomach contents was tested. Mammalian blood in the stomach of the medicinal blood leech Hirudo medicinalis gave satisfactory results. In the case of mixed blood samples from H. medicinalis, the identification of the host according to the electrophoretic patterns of the stomach contents failed as compared with an immunological method such as the Ouchterlony test. Medicinal blood leeches (H. medicinalis) collected in Istria Croatia, or bought in a pharmacy contained blood from cattle, horses, or frogs in their stomachs. Specimens of H. medicinalis from Lake Neusiedl or from the Seewinkel Austria, had sucked blood from mallards or frogs. Blood of cattle, mallards, and frogs was found in the stomachs of H. medicinalis coming from the National Park Kiskunsag Hungary. For the first time, horses were established as hosts for free-living specimens of H. medicinalis. A comparison of the weights of H. medicinalis bought in a pharmacy revealed that specimens containing frog blood in their stomachs weighed significantly less than those containing horse blood. These results confirmed the reports from Ssynewa (1944) concerning the breeding experiments. Probably, there is a change in hosts from the frog to warm-blooded animals during the life cycle of H. medicinalis. There were also significant differences in the weights of leeches as revealed by a comparison of the population from the Neusiedlersee with the leeches bought in the pharmacy. PMID- 8493251 TI - Ultrastructural evidence for dense granule exocytosis by first-generation merozoites of Eimeria tenella in vivo. PMID- 8493252 TI - Internal metacercarial cysts of Fasciola hepatica in the pulmonate snail Lymnaea truncatula. PMID- 8493253 TI - Chronic malnutrition: protein metabolism. PMID- 8493254 TI - The impact of gastrointestinal parasites on protein-energy malnutrition in man. AB - There is no doubt that at high intensity of infection, intestinal parasites can cause severe illness and the death of their hosts. Even with the high prevalence of these infections, however, such severe cases are rare and the norm is for low to moderate numbers of parasites which cause few if any overt symptoms. Nevertheless, it has been argued that by causing subtle reductions in appetite, absorption, digestion and acute-phase status and increasing intestinal nutrient losses, these low-level but long-term infections could be responsible for the persistent, poor nutritional status of so many children in Third World communities. Although geographically, high parasite prevalence occurs in conjunction with high levels of protein-energy malnutrition, attempts to establish a cause and effect relationship have had very limited success with many investigators being unable to demonstrate any detrimental consequence of infection. The unimpressive results might be explained to some extent by the unusual features of helminth infections such as rapid reinfection, the overdisperse distribution pattern and the uncertainty of a host inflammatory response, but they also suggest that A. lumbricoides (on which most studies have concentrated) may be of little nutritional importance. It seems likely that the more invasive parasites, e.g. the hookworms, S. stercoralis, T. trichiura and perhaps G. lamblia may have a greater impact and clearly more studies are required here. Safe, cheap and effective anthelmintics are now available and, on the grounds of disease prevention, there is a case for their nationwide use. However, from the available evidence, it would be unwise to expect that such programmes would make a significant impact on the nutritional status of children in Third World communities. PMID- 8493255 TI - Chronic undernutrition and the young. AB - The problem of chronic undernutrition and its direct and indirect effects, especially in Africa are multi-faceted and integrated, and have roots in socio economic, cultural, environmental, political, technological and other factors. In this scenario, the immediate victims are children, especially those under 5 years of age. There seems to be a vicious cycle of maternal malnutrition, infant death and high fertility as well as malnutrition, ill-health and low agricultural productivity in Africa. These make the situation serious and chronic. It means that the structures which bring about this problem need critical re-evaluation, particularly in terms of increased agricultural productivity, both in quantity and quality, and normal nutritional status. Increased production of staple and supplementary foods is now a widespread need in the African continent, as is population control. Experience has shown that nutrition is a complex and interacting phenomenon which is very much influenced by policies that affect socio-economic structures. Since the problem of hunger and malnutrition is a structural problem, nutrition may be regarded as an integral part of development planning. Higher priority may be given, therefore, to food and nutrition planning and their subsequent integration into national development plans, especially by taking into consideration the vulnerable groups which are the children in the population (Idusogie, 1977). PMID- 8493256 TI - Interactions between parasites and animal nutrition: the veterinary consequences. PMID- 8493257 TI - Metabolic consequences of intestinal parasitism. PMID- 8493258 TI - The role of zinc and vitamin A deficiency in diarrhoeal syndromes in developing countries. PMID- 8493259 TI - Vitamin undernutrition. PMID- 8493260 TI - Micronutrient undernutrition in British schoolchildren. PMID- 8493261 TI - Iron, infection and immune function. PMID- 8493262 TI - Aid programmes for malnutrition and the role of the nutritionist. PMID- 8493263 TI - Nutrition and health in the developing world: the Caribbean experience. PMID- 8493264 TI - 'Malnutrition, learning and behavior': 25 years on from the MIT symposium. PMID- 8493265 TI - Chronic undernutrition in pregnancy and lactation. PMID- 8493266 TI - Some aspects of the long-term effects of malnutrition on the behaviour of children in the Third World. PMID- 8493267 TI - Causes and consequences of dieting and anorexia. PMID- 8493268 TI - The behavioural effects of undernutrition in confined farm animals. AB - Results suggest that where the animal is unable to engage in functional feeding to reduce nutrient deficit, it may still continue to engage in feeding by directing its feeding behaviour to other alternative stimuli. If feeding is to be maintained where there are constraints on further intake, the alternative stimuli to food must be of sufficient incentive to prevent feeding being inhibited by other tendencies. Alternatives to food then are likely to be chosen on the basis of their sensory (incentive) qualities, and the precise form of feeding behaviour will depend on the interaction between the feeding tendency and the choice of available stimuli. Growing pigs offered single diets ad lib. and experiencing relatively mild deficits of specific-nutrients, may direct this behaviour towards pen-mates as alternative foraging stimuli, with blood resulting from this foraging activity acting as a further incentive to sustain the behaviour. If specific-nutrient deficits in growing pigs are generally mild then feeding may only be sustained in the presence of high incentives such as pen-mates. However, it is not always clear why stimuli such as pen-mates continue to attract foraging activity when they provide little of the deficient nutrients underlying the behaviour. Where the nutrient deficit is more extreme, such as in food-restricted sows and broiler breeders even stimuli with low incentive (e.g. chains, bars or walls) may be sufficient to maintain feeding tendency. The environment, by only allowing simple and non-complex behaviour to be performed, channels the expression of feeding behaviour into simple and repetitive stereotypic behaviours. Other behavioural processes such as arousal and sensitization may facilitate the marked persistence of stereotypies. PMID- 8493269 TI - The bioavailability and metabolism of aluminium compounds in man. PMID- 8493270 TI - The chemistry of aluminium in the gastrointestinal lumen and its uptake and absorption. PMID- 8493271 TI - Recent research on the causes of Alzheimer's disease. PMID- 8493272 TI - Nutrition information. PMID- 8493273 TI - Nutrition and migration: people on the move. PMID- 8493274 TI - Chronic undernutrition and the aged. PMID- 8493275 TI - Undernutrition and chronic disease: cancer. PMID- 8493276 TI - Micronutrients and longitudinal growth. AB - The present review has concentrated on the control of longitudinal growth and the relative importance of certain micronutrients. By far the most significant of these is 1.25(OH)2D3 which is now being recognized, not only for its role in maintaining Ca homeostasis, but also its major role in chondrocyte differentiation within the growth plate. PMID- 8493277 TI - Postnatal growth of gut and muscle: competitors or collaborators. PMID- 8493278 TI - Energy partitioning, tissue growth and appetite control. PMID- 8493279 TI - Nutrition and the immune system. PMID- 8493280 TI - The immunological effects of trauma. PMID- 8493281 TI - The effects of lipids on some aspects of the cellular immune response. PMID- 8493282 TI - [Amidinohydrazones as subjects of drug research. 2]. PMID- 8493283 TI - [Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)-formamidines corresponding alkyl esters with antianaphylactic activity]. AB - A lot of N-(2-carboxy-thieno[2,3-b]pyridin-3-yl)formamidines especially in form of their amine salts--were synthesized by reaction of 3-amino-thieno[2,3 b]pyridine-2-carboxylic acids with dimethylformamide/phosphoroxide chloride or by reaction of 4-oxo-4H-pyrido[3',2':4,5]thieno[3,2-d]1,3- oxazines with amines. Carboxylic acid alkylesters of this structure were yielded from 3-amino thieno[2,3-b]pyridine-2-carbonic acid alkylesters by reaction with dimethylformamide/phosphoroxide chloride or with N-formyl-piperidine or N-formyl morpholine and phosphoroxide chloride. The compounds showed antianaphylactic activity. PMID- 8493284 TI - Study of the in vitro penetration of the topical glucocorticoid betamethasone-17 valerate from solution-type gels into a multilayer membrane system. AB - The in vitro transport of betamethasone-17-valerate (1) into a multilayer membrane system has been investigated. Subsaturated formulations of 1 were studied as formed by mixing appropriate propylene glycol/water cosolvent systems. The AUC (drug concentration in acce ptor membrane as a function of time) and the diffusivity of the drug in the vehicle were used to evaluate the results of the in vitro transport. The importance and relationship between solubility, partition coefficient, and diffusivity for the process of in vitro penetration of 1 are discussed. PMID- 8493285 TI - In vitro micronucleus test of the cardioprotective agent stobadine. A genotoxicological study. AB - The genotoxic effect of stobadine (1) was studied in vitro using the micronucleus test. Hamster and human fibroblastoid cells were used. In hamster cells, the highest concentration of 1 (1.10(-3) mol/l) caused a significant elevatin in the number of micronuclei, while in human cells no positive response was found for either of the concentrations used. Stobadine had no genotoxic effect on human fibroblastoid cells. PMID- 8493286 TI - Interaction of ibuprofen with early chick embryogenesis. AB - The effects of ibuprofen (1) on the morphogenetic systems of the chick embryo were studied by means of the CHEST (Chick Embryotoxicity Screening Test). The subgerminal administration of doses of 0.03 mg 1 and larger ones induced a growth retardation of the caudal morphogenetic system (CMS). The administration of single effective doses of 1 subgerminally on the 2nd d and intraamniotically on the 3rd and 4th d of embryogenesis verified the beginning of the direct embryotoxicity range between doses of 0.003 to 0.03 mg/embryo. It presents in the theoretical extrapolation for mammals including man the dose limits between 10 and 100 mg.kg-1 of maternal weight. Embryotoxic manifestations (particularly embryolethality) were induced predominantly by the highest dose only. The developmental defects of the face, heart, brain, and the reduction limb defects were very rare. PMID- 8493287 TI - Comparison of local anesthetic activity of pentacaine (trapencaine) and some of its derivatives by three different techniques. AB - The local anesthetic potency of the carbanilic drug pentacaine (1; trapencaine) was compared to that of a series of its derivatives as well as procaine and cocaine. It is known that 1 exhibits potent local anesthetic, gastroprotective and antiulcer activities. The local anesthetic potency of the drugs under study was tested by three different techniques, i.e. analysis of compound action potential amplitude in rat sciatic nerve in vitro, duration of full anesthesia in rabbit cornea in vivo as well as in guinea-pig skin in vivo. The potency was expressed as drug concentration evoking either 50% reduction in action potential amplitude in the isolated nerve or anesthesia lasting for 20 min in the other two techniques. The most powerful anesthetics were found to be 1, K1905, and K2002 with their potency exceeding that of procaine and cocaine by 1-2 orders. The derivatives P1, P2, and P3 were much less effective, their potency being comparable to the two reference drugs. Although there were remarkable differences in the ranges of effective concentrations of particular drugs in the techniques used, a comparatively good agreement was found in the orders of the drug potencies. Plotting local anesthetic potency and drug lipophilicity revealed a good positive correlation between these two parameters in the group of the drugs tested. PMID- 8493288 TI - The influence of carbamate local anesthetics on the occurrence of experimental gastric ulcers. AB - Evaluation of the antiulcer effects of a series of 2-piperidineethylesters of o alkoxy-substituted phenylcarbamic acids were performed using two experimental models of gastric ulcers, e.g. induced by stress or by ligation of the pylor. It was found that these models were not identical. In the case of stress-induced ulcers, no experimental animal died as compared to the second experimental group with a 30% mortality rate due to the more frequent occurrence of ulcer perforations. Result similarities of both models could only be found with respect to the range of damage of the mucous membrane of the stomach. A premedication of rat with basic carbamates in the dose 20 mg.kg-1 p.o. resulted in a reduced incidence of stress- and ethanol-induced ulcerous lesions. The most significant antiulcer activity was found using compounds designated as the No. XIII, XVI and XIX. Pretreatment of rats with basic carbamates in the case of Shay ulcers has again resulted in a reduced range of ulcer lesions which was most expressive using compounds No. XVI and XIX. PMID- 8493289 TI - The effect of exogenous alpha-elastin on the DNA content in the chick embryos. PMID- 8493290 TI - Translocation of protein kinase C in human platelets by patients with chronic uremia. PMID- 8493291 TI - Tumour suppressor genes and molecular chaperones. AB - The two tumour suppressor genes that are most commonly inactivated in human cancer are the p53 gene on chromosome 17 and the retinoblastoma (Rb) gene on chromosome 11. Recent studies of both gene products suggest that they are able to act as powerful negative regulators of cell division. The Rb gene seems to exert this activity by physically complexing to a variety of specific transcription factors and inactivating their function. The capacity of Rb protein to bind these factors is regulated by phosphorylation. The Rb protein can therefore be seen to act as a chaperone for these factors. The p53 protein also may act in part by regulating transcription but may also interact directly with the DNA replication apparatus. The growth suppressive function of p53 is induced by DNA damage leading to an attractive model of p53 as an essential checkpoint control. The p53 protein interacts with members of the hsp70 chaperone family which we now show can regulate its function. PMID- 8493292 TI - A clinical trial of sleep deprivation in combination with antidepressant medication. AB - The literature suggests that sleep deprivation can potentiate the effect of antidepressant medication in depressed patients. However, the clinical efficacy of sleep deprivation has not been demonstrated definitively, in part because it is difficult to design an adequate control condition. We conducted a trial of sleep deprivation in 26 depressed patients who remained symptomatic despite 3 months of treatment with antidepressant medication. Since the literature indicates that early sleep deprivation (ESD), carried out in the first half of the night, is a less effective antidepressant than late sleep deprivation (LSD), carried out in the second half of the night, we designed a study that attempted to use ESD as a control condition for LSD. Patients were randomly assigned to ESD or LSD, received a total of 4 nights of sleep deprivation over 2 weeks, and were followed in clinic for the 3 subsequent weeks. ESD proved to be as effective an antidepressant as LSD, with the overall sample showing a mild, but statistically significant, response. There was a significant correlation between patients' acute response at the time of the first course of sleep deprivation treatments and their improvement over the course of the study. There were significant changes in plasma levels of thyroid stimulating hormone, free triiodothyronine, prolactin, and cortisol measured at 8 a.m. before and after sleep deprivation, and in the followup period, but there were no significant correlations between changes in hormonal levels and either acute or chronic response to sleep deprivation. PMID- 8493293 TI - Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together. AB - The relative importance of shared genes, shared environments, and individual specific environmental effects for monoamine oxidase (MAO) activity in thrombocytes was assessed in the Swedish Adoption/Twin Study of Aging. The sample consists of identical twins separated at an early age and reared apart (30 pairs), identical twins reared together (60 pairs), fraternal twins reared apart (66 pairs), and fraternal twins reared together (68 pairs), whose average age was 63.5 years; 49% were female. Consistent with the literature, the heritability of MAO activity was 0.77 and did not differ across cohort (under or over 63 years of age) or gender. Sharing rearing environments or similar experiences later in life does not result in familial similarity for MAO activity. PMID- 8493294 TI - A serine to glycine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein: no role in the genetic predisposition to bipolar affective disorder. AB - Association studies offer a promising tool to investigate the potential role of DNA sequence variation affecting the expression or sequence of proteins in susceptibility to common diseases. We determined the frequency of a DNA polymorphism resulting in a glycine to serine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein in a sample of 83 patients suffering from bipolar affective disorder and 100 control subjects. No significant differences between the groups were found. Thus, this substitution, which is the first sequence variation identified in the dopamine D3 receptor gene altering the amino acid sequence of the protein, can be regarded as a protein variant with no major effect on the susceptibility to bipolar affective disorder. PMID- 8493295 TI - Prospective assessment of electroencephalographic sleep in remitted major depression. AB - We studied 29 patients with major depression before treatment and then followed these patients prospectively with monthly electroencephalographic (EEG) sleep assessments after successful treatment. Most EEG sleep measures demonstrated no change from the episode throughout a prolonged period of clinical remission. When there was evidence of a change in EEG sleep measures, the effect was modest and due to only a small subset of patients. These findings contribute to the accumulating evidence that selected EEG sleep measures appear to be trait-like and may be useful in identifying individuals at risk for major depression. PMID- 8493296 TI - Comorbidity in panic disorder: II. Chronology of appearance and pathogenic comorbidity. AB - Ages of onset and the sequence of appearance of panic disorder (PD) and comorbid conditions were determined in a sample of 54 patients with the principal DSM-III R diagnosis of PD. The onset of PD was earlier in patients with moderate to severe agoraphobia (AG) than in panic patients without AG. Patients with alcohol abuse and drug abuse before the onset of PD also had a tendency to develop PD earlier, which suggests that these conditions might have specifically predisposed to PD. All comorbid disorders, except for major depression, were more likely to precede the onset of PD so that, more often than not, PD appeared as a chronologically secondary condition. However, it was found that only for primary substance abuse such a temporal relationship might denote etiologic relatedness to PD, because of the reduced temporal distance between the onset of primary substance abuse and secondary PD. PMID- 8493297 TI - Visual pattern integration as a function of antidepressant medication in depressed patients. AB - On the basis of an earlier study that reported depressed patients to be superior to normal control subjects in visual iconic integration, the present investigation sought to determine if this finding was replicable and if medication produced it. Newly admitted depressed patients entering drug treatment, depressed patients already in drug treatment, and healthy control subjects were twice tested, with a 5-week interval between sessions. Fully medicated depressed patients, whether newly admitted or already in drug treatment, were superior to normal control subjects in visual integration, and healthy control subjects were superior to depressed patients just entering treatment. At the first testing, the number of days of medication treatment was significantly correlated with the adequacy of visual integration. PMID- 8493298 TI - The acute effects of starvation on 6-sulphatoxy-melatonin output in subgroups of patients with anorexia nervosa. AB - Sequential measures of daytime and nighttime sulphatoxy-melatonin (aMT6s) in 10 female patients with anorexia nervosa (AN) and 12 female patients with concurrent AN with bulimic symptoms (AN + BN) were compared with 13 female control subjects. The AN + BN group displayed a significant increase in aMT6s output in the acutely symptomatic state compared with both AN patients and controls. However, there were no subsequent differences after 7 or 14 days between the two patient groups. The AN + BN group also initially demonstrated a significant increase in daytime output of aMT6s compared to nighttime with a trend toward reversing this pattern after 7 and 14 days. Altered melatonin output may influence the course of illness or reflect greater disruption of circadian rhythm in those anorexic patients who also binge and purge compared to restricting anorexics. PMID- 8493299 TI - Psychosexual behavior in hypopituitary men: a controlled comparison of gonadotropin and testosterone replacement. AB - Nine gonadotropin-deficient hypopituitary men were cycled through periods of treatment with testosterone (T), gonadotropin (Gn), and placebo (Pl) using a blind cross-over design. Self-reports of sexual behavior, recordings of nocturnal penile tumescence (NPT), and sex steroid levels were obtained during each treatment period. Subjects had significantly higher plasma T during the T and Gn treatments than during the control periods. Similarly, self-reported frequency of ejaculation and ratings of libido as well as duration measures of NPT were significantly higher on T and Gn. Two thirds of the sample had no sociosexual experience. Behavioral differences between the T and Gn periods were minimal. These data support the hypothesis that Gn and T are equally effective in stimulating specific aspects of male psychosexual behavior. PMID- 8493300 TI - Sex steroids, sexual behavior, and selection attention for erotic stimuli in women using oral contraceptives. AB - The relationship between sex steroids and sexual behavior was examined in 19 oral contraceptive users. Retrospective assessment of sexual attitudes were obtained and women completed daily ratings of sexual behavior and well-being for 28 days. Plasma levels of free testosterone (T), estradiol, and progesterone were measured at weekly intervals. In addition, women performed a novel selective attention task designed to measure the strength of the tendency to be distracted by sexual stimuli. Multiple regression analyses using average sexual behavior variables as dependent variables, and hormone levels sexual attitudes and well-being as predictor variables, showed that free T was strongly and positively associated with sexual desire, sexual thoughts, and anticipation of sexual activity. A role for T in attention to sexual stimuli was also supported by the positive correlation between free T and the bias for sexual stimuli in a subgroup of women. These results are consistent with the hypothesis that T may enhance cognitive aspects of women's sexual behavior. PMID- 8493301 TI - Psychopharmacologic issues in organ transplantation. Part I: Pharmacokinetics in organ failure and psychiatric aspects of immunosuppressants and anti-infectious agents. AB - This article discusses pharmacokinetics and pharmacodynamics during hepatic, renal, and cardiovascular insufficiencies. Hepatic metabolism of psychotropic drugs and of drugs commonly used in transplant patients that have neuropsychiatric side effects is discussed. Neuropsychiatric effects of immunosuppressant agents, including cyclosporine, corticosteroids, azathioprine, OKT3, and FK 506, are reviewed. Certain infections occur more often in immunosuppressed patients; their treatment with antiviral, antifungal, and antibiotic drugs may have neuropsychiatric consequences. Because of altered drug sensitivities and metabolism, drug interactions, and severe medical illness, most drugs are used in reduced doses. PMID- 8493302 TI - Psychopathology of pancreatic cancer. A psychobiologic probe. AB - Reports of characteristic psychiatric symptoms occurring in patients with pancreatic cancer appear regularly in the literature. A review of this literature reveals that symptoms of depression and/or anxiety may appear in approximately 50% of patients with pancreatic cancer before the diagnosis is made. This review proposes that the psychopathology of pancreatic tumors may be linked to tumor induced changes in neuroendocrine or acid-base systems. Although confirmatory data are lacking, informed speculation centers on the potential role of adrenocorticotropic hormone, parathyroid hormone, thyrotropin-releasing hormone, glucagon, serotonin, insulin, and bicarbonate in the production of depression and/or anxiety in this disease. Elucidation of the pathophysiology of the psychiatric symptoms in patients with pancreatic cancer may provide a marker for early diagnosis of pancreatic neoplasia as well as a probe into the biologic bases of depression and anxiety. PMID- 8493303 TI - The pedestrian trauma patient. Perspectives from a psychiatric consultation service. AB - The hospital course of adult pedestrians injured by automobiles and treated by a university trauma service over a 12-month period was reviewed to evaluate the prevalence, recognition, and intervention of substance use and suicidal behavior. The study showed that the pedestrian trauma patient had a dramatically high rate of substance use and a surprisingly low index of suspicion of suicide attempt by the treatment team as a cause of the accident. Appropriate intervention might greatly reduce the financial and human cost of trauma care, but awareness and identification of these risk factors must be taught first. PMID- 8493304 TI - Prevalence of psychiatric disorders in patients with irritable bowel syndrome. AB - Thirty-five patients with irritable bowel syndrome were referred from the gastroenterology service and underwent structured psychiatric interviews to assess the prevalence of psychiatric illness. Thirty-three (94%) of 35 patients were found to have a lifetime prevalence of any Axis I disorder; the predominant diagnoses were mood and anxiety disorders. Theoretical and practical implications of these findings are discussed. PMID- 8493305 TI - Liver transplantation using living donors. Preliminary donor psychiatric outcomes. AB - Twenty liver transplantations to sick infants from living-donor relatives were performed over a 16-month period. Before the operation, donors were screened psychiatrically by interview and psychological testing. Donor outcomes were assessed postoperatively to evaluate adverse psychiatric outcomes and to attempt a correlation with preoperative findings. There were three significant donor problems in the immediate postoperative period, two marital dissolutions and one adjustment disorder, as well as several other minor problems. These results are examined in light of past observations about living-donor renal transplantations and pediatric transplantation in general. PMID- 8493306 TI - Psychological response to breast reconstruction. Expectations for and impact on postmastectomy functioning. AB - Breast reconstruction is being considered by increasing numbers of breast cancer patients. Recent controversy over the relative risk to benefit of breast implants suggests a need for more information about who seeks reconstruction, why, and its impact on postmastectomy functioning. Eighty-three women undergoing reconstructive surgery were assessed with respect to surgical and psychological status. Evaluations were made at the time of consultation for breast reconstruction and repeated 2 months or more postsurgery. Findings highlight the overwhelmingly positive effects of postmastectomy breast reconstruction and provide information useful to those counseling or following breast cancer patients who pursue this option. PMID- 8493307 TI - Psychiatric diagnosis and the surgical outcome of pancreas transplantation in patients with type I diabetes mellitus. AB - To examine the role of psychiatric diagnosis in the surgical outcome of pancreas transplantation, we studied candidates with type I diabetes mellitus. Eighty of 140 candidates underwent transplantation. Survival analysis found the extent of human leukocyte antigen-DR (HLA-DR) matching, two diagnoses, and patients' perceived support from first-degree relatives to be related to duration of full graft function. Lifetime diagnoses of tobacco use disorder (P = 0.029) and alcohol abuse/dependence (P = 0.006) were associated with less favorable outcomes; perceived support was associated with positive outcomes (P = 0.048). Subsequent analysis suggested that the four variables independently and directly affect outcome. PMID- 8493308 TI - Should we shift the name for "consultation-liaison" to "medical-surgical" psychiatry, "psychiatry in medicine and surgery," or some other term? PMID- 8493309 TI - Hospital management of a patient with intractable factitious disorder. PMID- 8493310 TI - Conversion disorder presenting as primary fibromyalgia. PMID- 8493311 TI - Buspirone for myoclonus, obsessive fears, and confusion. PMID- 8493312 TI - Major depressive disorder in patients with the implantable cardioverter defibrillator. Two cases treated with ECT. PMID- 8493313 TI - Postpartum onset of obsessive-compulsive disorder. PMID- 8493314 TI - Fenfluramine and trichotillomania. PMID- 8493315 TI - Progestin treatment for obsessive-compulsive disorder. PMID- 8493316 TI - Caveat to nurses in "John Does" organ harvests. PMID- 8493317 TI - "Asleep on duty" record impacts delay in delivery case. Case in point: St. Paul Medical Center v. Cecil (842 S.W.2d 808--TX [1992]). PMID- 8493318 TI - Legal case briefs for nurses. NY: refusal to stay for additional shift: "abandonment" charged--suspension results. AL: substance abuse--licence revocation: highly qualified and talented nurse. PMID- 8493319 TI - Patient sues nurse for failure to obtain informed consent. Case in point: Foflygen v. R. Zemel, M.D. 615A. 2d 1345--PA (1992). PMID- 8493320 TI - Doctor "shocks" nurse: $1.2 million verdict. PMID- 8493321 TI - Nurse fails to communicate: catastrophic results. Case in point: White v. Methodist Hospital South 844 S.W. 2d 642--TN (1992). PMID- 8493322 TI - Legal case briefs for nurses. GA: is doctor "expert" on nursing practice?: must experts state standards of care? NY: Dr. accused of sexual misconduct: nurse's exculpatory testimony sought. PMID- 8493323 TI - Nurse liability for dispensing meds "as ordered". Case in point: Navarro v. George 615A. 2d 890--PA (1992). PMID- 8493324 TI - Early and late flash-induced field responses correspond to ON and OFF receptive field components in hamster superior colliculus. PMID- 8493325 TI - Functional organization of the projections from the rabbit's superior colliculus to the lateral posterior nucleus. PMID- 8493326 TI - Multiple visual areas in the posterior parietal cortex of primates. PMID- 8493327 TI - Corticotectal relationships: direct and "indirect" corticotectal pathways. PMID- 8493328 TI - Light sensitivity, adaptation and saturation in mammalian rods. PMID- 8493329 TI - Abnormal visual experience and spatio-temporal properties of area 18 neurones in the cat. PMID- 8493330 TI - Visual behavior following lesion of phasic W-fibers in the cat's optic tract. PMID- 8493331 TI - Visuotopic organization of corticocortical connections in the visual system. PMID- 8493332 TI - Disparity coding in the cat: a comparison between areas 17-18 and area 19. PMID- 8493333 TI - Cortical convergence of ON- and OFF-pathways and functional adaptation of receptive field organization in cat area 17. PMID- 8493334 TI - Temporal covariance of postsynaptic membrane potential and synaptic input--role in synaptic efficacy in visual cortex. PMID- 8493335 TI - Potentiation of the extrageniculo-striate pathway: a possible role in visual pattern discrimination. PMID- 8493336 TI - The development of visual cortical properties depends on visuo-proprioceptive congruence. PMID- 8493337 TI - Reorganization processes in the visual cortex also depend on visual experience in the adult cat. PMID- 8493338 TI - Extraretinal modulation of geniculate neuronal activity by conditioning. PMID- 8493339 TI - The properties of the long-term potentiation (LTP) in the superior colliculus. AB - (1) Postsynaptic potential (PSP) was recorded in the SGL of guinea pig SC slices after stimulation to the OL. (2) Tetanic stimulation (optimum parameter: 50 Hz in frequency, 20 sec in duration) to the OL induced LTP in the PSP of SGL. (3) NMDA receptor antagonist MK801 inhibited the LTP occurrence but D-APV and gamma-DGG masked the appearance of LTP, suggesting that the mode of involvement of the NMDA receptor for LTP formation in the SC may be different from that reported in the hippocampus. (4) Protein kinase C inhibitors such as H-7, polymixin B and K-252a inhibited the maintenance of LTP. (5) Application of GABA prevented the occurrence of LTP and bicuculline facilitated the formation of LTP. (6) In in vivo preparations of the rat, the LTP in the SC was only elicited by tetanic stimulation to the optic nerve either when the visual cortical are ipsilateral to the SC tested was ablated or when picrotoxin was administered to the animal before tetanic stimulation. PMID- 8493340 TI - The nature of synaptic plasticity in the visual cortex of kittens. An electrophysiological analysis in vitro. PMID- 8493341 TI - The analysis of visual space by the lateral intraparietal area of the monkey: the role of extraretinal signals. PMID- 8493342 TI - Visual pathways to perception and action. PMID- 8493343 TI - Macaque ganglion cells and spatial vision. PMID- 8493344 TI - Amygdalar and hippocampal neuron responses related to recognition and memory in monkey. PMID- 8493345 TI - Responses of monkey basal forebrain neurons during visual discrimination task. PMID- 8493346 TI - Functional contributions of the primate pulvinar. AB - One of the major tasks facing the central nervous system is choosing which sensory events to use for perception and directed behavior. All organisms live in a rich sensory environment, and it is impossible to attend and respond to everything. Certain brain regions and systems must evaluate sensory signals and then determine which are salient. Based on recent data derived from diverse studies of the pulvinar of primates, it is the hypothesis of this paper that a major role of the pulvinar is to participate in the generation of visual salience, those processes which precede perception and action. This process of salience generation makes use of two broad mechanisms, the suppression of noise and the enhancement of significant signals. Outlined above are experiments which show that the visual activity which might be caused by eye movements is filtered from some pulvinar cells. Visual responses associated with certain directions of gaze are removed. Finally the ability to suppress the activity of distracting visual stimuli is dependent on the integrity of the pulvinar. Conversely, there are neurons within the pulvinar which respond best when animals actively select and thus engender certain stimuli with salience. Modulation of pulvinar functioning with transmitter-related drugs changes performance as if salience is being modulated. Humans and monkeys with destruction of the pulvinar behave as if they too cannot create or evaluate salience. Finally, when salience is demanded of humans by making their visual tasks more demanding, there is an increase in PET activity. The hypothesis here is that the pulvinar functions as an early center for the generation of visual salience. This is similar to the view of striate cortex as an early integration stage for the basic elements of visual processing (Hubel and Wiesel, 1968; Zeki, 1976; Allman et al., 1981). Vision does not take place within the complex microstructure of striate neurons, but all of the essential components are present there, and these are distributed to other cortical areas which construct specific aspects of visual perception. Similarly, regions of the pulvinar contain building blocks for visual/behavioral/oculomotor integration which they distribute to various cortical sites for shifts of attention and other types of response specification. When an organism must determine external visual salience, there are neurons within the pulvinar which signal this. Since the major efferents of these thalamic regions are the visual cortices (Benevento and Rezak, 1976; Lin and Kaas, 1979; Kennedy and Bullier, 1985), our present hypothesis is that these signals are used for the construction of visuomotor and visuo-perceptual states.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8493347 TI - Orientation discrimination in the cat and its cortical loci. PMID- 8493348 TI - Neuronal signals of importance to the performance of visual recognition memory tasks: evidence from recordings of single neurones in the medial thalamus of primates. PMID- 8493349 TI - Colour vision: isolating mechanisms in overlapping streams. PMID- 8493350 TI - Responses of monkey infero-temporal units in an orientation discrimination task. PMID- 8493351 TI - Blindsight: neurons and behaviour. PMID- 8493352 TI - The neurophysiological correlates of colour induction, colour and brightness contrast. AB - Psychophysical experiments suggest that colour contrast and colour induction by surround lights can be explained as brightness contrasts (darkness induction) in the spectral region of the surround colour. It follows from this model that a chromatic surround reduces the gain of receptor-ganglion cell channels if the surround colour is in their excitatory spectral region. Thus, a green-sensitive cell (G+/R- or WS in our nomenclature) would respond less to a blue-green stimulus flashed into its receptive field when the surround (5 degrees/20 degrees inner/outer diameter) is illuminated with blue light. Neurophysiological experiments show that this is indeed the case and that such surround-induced response changes are present already in relay cells of the parvocellular layers of the lateral geniculate nucleus (P-LGN) and their retinal afferents. These surround-induced response changes are in qualitative and quantitative agreement with psychophysical experiments. Since the neuronal signal for white consists of a balanced excitation of the M-cone excited, green-blue-sensitive WS-cells and the L-cone excited, yellow-red-sensitive WL-cells, the findings also explain colour induction on white surfaces as well as coloured shadows: during blue surround illumination, white signals from the WS-cells, and during red surround the white signals from the WL-cells are reduced. The neurophysiological surround effects on P-LGN cells are identical but weaker than those produced by light of the same colour shone into the receptive field centres. They are therefore undistinguishable from direct adaptation of those receptors which feed directly into the receptive field of the respective cells. This suggests that they are caused by scattered light reaching the receptive field from the surround. PMID- 8493353 TI - Neuronal representations, assemblies and temporal coherence. PMID- 8493354 TI - Functional architecture of rodent superior colliculus: relevance of multiple output channels. PMID- 8493355 TI - The visually responsive neuron and beyond: multisensory integration in cat and monkey. PMID- 8493356 TI - Sensory integration in the deep layers of superior colliculus. PMID- 8493357 TI - Pathophysiology of pancreatitis: the role of prostaglandins. PMID- 8493358 TI - Cecal ligation and puncture is associated with pulmonary injury in the rat: role of cyclooxygenase pathway products. AB - The present studies evaluated the role cyclooxygenase products play in bacterial sepsis induced pulmonary injury in the rat. Lung injury was assessed by determining the pulmonary capillary filtration coefficient (Kf) and the lung lavage protein concentration four and 18 hours after cecal ligation and puncture. Four hours after cecal ligation, the Kf was unchanged from control, however, by 18 hours, the Kf was increased 171% (p < .05). Similarly, lung lavage protein levels were unchanged four hours after cecal ligation but were significantly (p < .05) elevated at 18 hours. On the other hand, pulmonary lavage immunoreactive thromboxane B2 (iTXB2) levels were increased both four and 18 hours after the initiation of sepsis. In order to determine if cyclooxygenase products played a role in the sepsis associated lung injury, ibuprofen was administered prior to cecal ligation. Ibuprofen pretreatment prevented the sepsis associated increase in both Kf and lung lavage protein concentration. These studies suggest that bacterial sepsis in the rat is associated with pulmonary injury and that early administration of ibuprofen ameliorates this damage. PMID- 8493359 TI - Biochemical changes in human cervical connective tissue after intracervical application of prostaglandin E2. AB - Cervical biopsies were taken during the first trimester from primigravidae and plurigravidae at different time points after intracervical application of prostaglandin E2-gel. Collagenase activity was determined by a highly specific technique using native, triple helical collagen as substrate. Elastase-alpha 1 proteinase-inhibitor complex (elastase) was measured by a commercially available assay, and glycosaminoglycan (GAG) analyses were performed as described by Greiling et al. (5, 6). The maximum activity of collagenase was found 2 hours after PGE2 application in plurigravidae and 4 hours after application in primigravidae. Elastase activity rose nearly 7-fold to maximum values 4 hours after PGE2 application. The total GAG concentrations and the dermatan sulfate concentrations increased by approximately 10%, while the hyaluronic acid concentrations were found to be elevated significantly by nearly 50% in the PGE2 primed cervices. We conclude that a time-dependent enzymatic collagen degradation by collagenases and other proteinases and an increase in hyaluronic acid concentrations are the significant biochemical events underlying PG-induced cervical ripening. PMID- 8493360 TI - Effect of culture conditions on mast cell eicosanoid synthesis. AB - When mast cells are grown in culture from mouse bone marrow cells, some cells are in suspension and some attach. The cells in suspension released leukotrienes and thromboxane when stimulated. Removal from the attached cells increased eicosanoid formation in the suspended cells two- to six-fold. The upregulation of arachidonic acid metabolism seemed to be due to an increase in phospholipase activity. The attached cells resembled macrophages in morphology, but stained positively for mast cells and produced PGD2 an arachidonic acid metabolite which is characteristic for mast cells. The attached cells did not synthesize eicosanoids when stimulated with IgE/antigen or A23187. Addition of arachidonic acid caused cyclooxygenase product formation but not leukotrienes. No 5 lipoxygenase was detected by immunoblot analysis. Lack of eicosanoid synthesis was, therefore, due to the loss of 5-lipoxygenase and phospholipase activity, while the cyclooxygenase was preserved. These experiments demonstrate that attachment of mast cells to plastic can significantly alter their eicosanoid metabolism. PMID- 8493361 TI - [Abdominal Doppler echography. Pathologic arterial signals]. AB - In this paper, the features are reported of the major pathological flow signals obtained during Doppler examinations of abdominal vessels. The patterns are correlated with the pathological lesions which may cause them, as well as with the underlying changes in arterial hemodynamics. Pathological flow signals are divided into three groups, according to the sites where the lesions producing them are located. a) Lesions of the vessel walls. In this group, both widening of spectrum due to disturbed flow and increased blood velocity from vessel stenosis are presented. Also flow alterations occurring in aneurysms (reduction of flow velocity and presence of vorticous flow) are discussed. b) Changes in peripheral resistances. Peripheral resistances may either increase or decrease due to a variety of diseases. Parenchymal edema, compression, infiltration, as well as small vessel disease, may increase vascular impedance. Fall of vascular resistances may be observed in inflammation or in arteriovenous fistulas either large (congenital or hemodialysis fistulas) or microscopic, as in many hypervascular tumors. A typical "to and fro" flow pattern was seen in vessels where flow resistance is overcome only during systole, such as in arterial pseudoaneurysms. c) Changes in rhythm or strength of the heartbeat, cardiac valvular diseases, postocclusive flow. A variety of pathological findings may be observed in these conditions. Peculiar changes in the waveforms are seen with variations in heart frequency. Changes may be detected also in aortic valvular diseases, with retrograde flow observed in patients with aortic insufficiency. Low and slow flow are seen in post-stenotic and/or postocclusive vessels. PMID- 8493362 TI - [Abdominal aorta: role of angiography with magnetic resonance]. AB - The diagnostic role of Magnetic Resonance angiography (MRA) was investigated in the study of the abdominal aorta. To obviate the problems relative to motion and respiratory artifacts, the TOF 2D (FISP 2D) technique was employed, together with a superconductive 1.5 T magnet. Fourteen volunteers were studied. The images acquired on the coronal and sagittal planes were processed according to MIP and target MIP, with a rotation on the z axis. The abdominal aorta was clearly demonstrated in 100% of cases, the celiac trunk in 42.8% of cases on coronal and in 100% on sagittal images. The superior mesenteric artery was depicted in 35.7% of cases on coronal and in 100% of subjects on sagittal acquisitions. The renal and iliac arteries were demonstrated in 100% of cases on coronal images only, while dorso-spinal and lumbar arteries were always clearly depicted on sagittal scans only. To evaluate the diagnostic reliability of MRA, 6 patients with abdominal aortic aneurysms were also studied and angiography and surgery were assumed as the gold standard. In all cases MRA yielded similar information to angiography and surgery as to aneurysm extent, vessel involvement and left renal vein course; moreover, MRA allowed the assessment of both the thrombotic and the calcific components of the aneurysm. Unenhanced MRA with the TOF 2D technique allows the detailed depiction of the aorta in about 20 minutes. Our preliminary results in the study of aneurysms are encouraging relative to the future diagnostic role of MRA in the abdominal aorta. PMID- 8493363 TI - [Angiography with magnetic resonance++ of the renal arteries: bidimensional versus tridimensional "time of flight" technique]. AB - Twenty volunteers were examined by means of 2D and 3D time of flight (TOF) Magnetic Resonance angiography (MRA) of the renal arteries. The possible diagnostic applications of MRA were also evaluated in 6 patients with renovascular diseases. MRA examinations of the renal arteries were performed with a 1.5 T superconductive magnet (Magnetom Siemens) and circular body coil. Ten volunteers were studied with 3D FISP sequences (FA 25 degrees, TR 40 ms, TE 7 ms, ST 1 mm, Ma 256 x 256, FOV 500); the images were acquired on the axial plane and were rotated, in MIP and target MIP, on the axial (z) and sagittal (x) axes. The other 10 volunteers were studied with 2D FLASH sequences (FA 18 degrees, TR 300 ms, TE 8 ms, ST 4 mm, overlap 1 mm, Ma 256 x 256, FOV 500); the images were acquired on the axial and coronal planes and were rotated, in MIP and target MIP, on the axial (z) and sagittal (x) axes. The ostium and proximal segments (1-15 mm) were always easily identified with 2D and 3D sequences, the distal segments (16-35 mm) were also clearly demonstrated in 11 cases with 3D (55%) and in 16 cases with 2D (85%) sequences. The bifurcations and branch vessels of the renal arteries were easily depicted with 3D TOF sequences in 7 cases only. Combined 3D and 2D TOF images permitted the thorough evaluation of the renal arteries. In renovascular diseases, 2D and 3D TOF images clearly demonstrated occlusions and stenoses of the proximal segment (1-15 mm). 2D TOF sequences only permitted the visualization of a case of fibromuscular dysplasia in the distal segment. Our results suggest that 2D and 3D TOF MRA exhibits good potentials as a noninvasive screening technique for the evaluation of renovascular diseases. PMID- 8493364 TI - [Deep venous thrombosis of the legs. Diagnostic results comparing the duplex and the color-Doppler methods]. AB - Thirty-eight patients (45 limbs on the whole) with clinical suspicion of deep venous thrombosis in the lower limbs were examined with duplex US and color Doppler flow mapping. The results were compared with those of ascending phlebography used as a reference. Disease sites included distal localizations, limited to the leg, with no involvement of the popliteal vein, and proximal localizations, involving the popliteal vein to the iliac segment. In case of proximal thrombosis, duplex US had 81% sensitivity, 93% specificity, 86% positive and 90% negative predictive values. Color-Doppler flow mapping had 87% sensitivity, 96% specificity, 93% positive and negative predictive values. In case of distal localizations, the results were poorer with both methods; duplex sensitivity decreased to 60% and specificity to 83% with 64% positive and 80% negative predictive values. Color-Doppler results were slightly higher, with 80% sensitivity, 93% specificity, 85% positive and 90% negative predictive values. Thus, the authors believe color-Doppler flow mapping to be adequate as the imaging method of choice when deep venous thrombosis is suspected. Color-Doppler imaging yields better results in distal localizations and makes the examination easier, quicker and more panoramic. Phlebography should be employed in questionable cases and is required for the diagnosis of limited thromboses, which are at risk for embolism, as those we observed in the adductor canal, which are difficult to diagnose with US. PMID- 8493365 TI - [Diagnostic imaging of acute leukemia in childhood. Description of 5 cases with unusual onset]. AB - The authors, after reviewing the main features of the so called "leukemic osteopathy", remark how the natural history of leukoses has changed thanks to progress in both diagnosis and treatment. Indeed, the condition is now diagnosed early and its remission is quick. Thus, the cases with X-ray-evident bone involvement are quite uncommon: hence the need to use, at AL onset, imaging techniques which are more sensitive to bone marrow changes. To this purpose, MR imaging has proved a valuable technique which can demonstrate even the early stages of pathologic conditions affecting bone marrow. PMID- 8493366 TI - [Computed tomography in the follow-up of interstitial lung disease in progressive systemic sclerosis]. AB - Progressive systemic sclerosis (PSS) is a chronic multisystemic disease characterized by vascular changes, lung fibrosis and skin conditions. The lung is one of the most commonly involved organs in the patients suffering from this disease. Lung changes, along with heart involvement, represent one of the major causes of death in PSS patients. CT and high-resolution computed tomography (HRCT) scans and chest radiographs were obtained in 26 patients with PSS. The evaluation of chest films included the assessment of an average profusion score. The HRCT evaluation included pattern, extent and distribution of the disease. HRCT scans showed thickened septal lines in all patients and parallel subpleural lines in 6 patients (23%), while ground-glass opacification was seen in 2 cases (7.6%). Honeycomb pattern was observed in 8 patients (31%). Chest films showed definite interstitial opacification patterns in 8 cases only; 6 radiographs were equivocal and 12 (46%) normal. Five patients were followed 6 months to 3 years: 2 of them exhibited parallel worsening of skin conditions and of CT patterns, while X-ray findings in the chest were unchanged. In 2 cases skin and lung involvement were different (skin worsening and unchanged lung patterns, or viceversa). Finally, in 1 patient, the presence of patchy areas of air-space consolidation without air cysts on second-look was more consistent with bronchiolitis obliterans organizing pneumonia. PMID- 8493367 TI - [Diagnostic imaging in non-palpable breast lesions. Targeted++ ultrasonography versus direct radiologic magnification]. AB - The main target of mammography in asymptomatic women is the early diagnosis, or rather the identification, of non-palpable breast cancers. Doubtful or suspicious findings on conventional mammograms with no clinical evidence call for radiologic or other complementary imaging techniques to assess the exact lesion nature. Direct magnification and US are targeted techniques to employ as additional investigations after conventional mammography. Fifty consecutive patients were referred to our department of radiology for the preoperative localization of non palpable breast lesions previously identified on conventional mammograms. The diagnostic or complementary roles of direct magnification and of US were thus investigated. US was always repeated during the preoperative localization; a 10 MHz immersion sectorial probe was used. Magnification was performed if absent or poor in conventional mammograms. The contribution of each technique to conventional mammography was graded as valuable (A), medium (B), or null (C). The lesions were grouped according to their structure: microcalcifications (a), nodules (b), scars (c), and complex lesions (a+b, a+c, b+c, ecc.). Six cases are included in our series which had been diagnosed as questionable or suspicious on previous mammograms. In our department, they were diagnosed as benign. Two of them were operated on because biopsy was required by the gynecologist and the other underwent stereotaxic FNB: negative cytology was considered the final diagnosis. Forty-six histologic and 4 cytologic examinations diagnosed 25 malignant and 25 benign lesions. Direct magnification was of great value in all cases, whereas US was useless in microcalcifications and useful in nodular or complex lesions, especially those with a nodular component. However, the incidence of US false-negatives was high, even in very suspicious cases on mammography, which suggests that US negativity cannot be considered an adequate sign to rule malignancy out. PMID- 8493368 TI - [Transvaginal echography in the study of the rectum. A new method with rectal distension with water]. AB - Transrectal sonography (TRUS) accurately assesses the depth of invasion in the staging of rectal carcinomas. However, the method is limited in the evaluation of upper rectal and highly stenotic rectal cancers. These conditions can be demonstrated in female patients by transvaginal sonography (TVUS) with a 5-MHz convex probe. Conventional TVUS becomes even more accurate when the rectum is distended with water. Twenty-one asymptomatic female patients were examined in a prospective study to assess the value of conventional versus water-distended TVUS. Water improves rectal depiction because it eliminates air and fecal artifacts. In our series, the rectum was demonstrated from anum to rectosigmoid junction in all cases. The whole rectal outline could also be demonstrated. Besides rectal lumen evaluation, the method allowed rectal wall layers and perirectal fat to be detailed. Subsequently, 14 female patients were examined--8 during the preoperative staging and 6 during the follow-up. In preoperative patients, the extent of stenosing rectal cancer and perirectal fat infiltration were assessed; in postoperative patients rectal recurrences were excluded. In conclusion, TVUS with rectal distension by means of water is a new diagnostic procedure which can markedly improve the US imaging of highly stenosing rectal cancers. PMID- 8493369 TI - [Role of computed tomography in splenic blunt trauma]. AB - The CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with splenic blunt trauma were reviewed. CT examinations had been made at different times after trauma. The CT images were grouped according to the time of examination and both structure and densitometry were evaluated in all lesions. In all cases CT findings were correlated with surgical and pathologic data. The patients were divided into two groups: group I included 11 subjects in whom CT had been performed within 48 hours following trauma and group II included 7 patients who had undergone CT at different times after trauma (3-13 days; mean: 6.5 days). All the lesions in group I exhibited blurred outlines, while the lesions in group II had clear-cut margins. The lesions in group I were always hyperdense while those in group II were hypodense. CT diagnosis was always in agreement with surgical findings. In conclusion, we confirm the value of CT in the examination of splenic lesions by blunt abdominal trauma. The evolution of splenic lesions is usually typical: CT yields useful information for injury evaluation and is therefore very important to plan treatment. We believe that CT should be performed as soon as possible, even on the basis of minor clinical and laboratory data. PMID- 8493370 TI - [Dynamic computed tomography in the prognostic assessment of acute pancreatitis]. AB - Pancreatic necrosis is a well-known risk factor for infectious complications in the patients affected with acute pancreatitis. Dynamic CT with i.v. administration of a large bolus of contrast medium can establish the diagnosis of necrotizing pancreatitis. A series of 49 cases of severe acute pancreatitis was reviewed, and early CT investigations were seen to fail to detect pancreatic necrosis in 22 instances, versus 27 positive cases. In the group of patients with no necrosis, the clinical course was uneventful or characterized by mild complications which regressed spontaneously or by means of adjuvant medical treatment. On the contrary, 17 patients with necrotizing pancreatitis developed severe complications requiring intensive treatment. These complications occurred in 50% of the patients with < 50% of pancreatic necrosis, while the figure rose to 77% whenever more extensive involvement was observed. Our results show that the presence and extent of pancreatic necrosis must be diagnosed as early as possible for prognostic and therapeutic purposes; this can be done by the routinary use of dynamic CT with the administration of large amounts of contrast media at high flow rates. PMID- 8493371 TI - [Comparison of Gunther, Filcard and LGM definitive caval filters. Our experience]. AB - The authors report their experience with 30 caval filters placed throughout 3 years, and compare it with the data from the literature. In 8 patients (26.5%) Gunther filters were used, in 16 cases (53.5%) Filcard filters (4 DF-01 and 12 DF 04) and finally the last 6 patients (20%) were treated with LGM filters. In 18 cases (60%) the filters were positioned through right common femoral vein, whereas in the remaining 12 patients (40%) they were placed through the right internal jugular vein. Early complications were 1 mispositioning (3.3%) with a LGM filter, 2 incomplete opening (6.6%) of Filcard DF-01 filters, 3 significant tiltings (10%) with Filcard DF-04 filters. One patient (3.3%) died one week after the placement of a Gunther filter. The radiologic follow-up, which included controls with conventional radiology, US, cavography, MR and CT revealed no later complications. All the filters exhibited both advantages and disadvantages. Although all the filters commonly in use are effective to prevent pulmonary embolism, further experience is necessary to find out the "ideal" filter. PMID- 8493372 TI - [Bone disease in multiple myeloma. Analysis of 253 controlled cases, with reappraisal of diagnostic criteria and current imaging techniques]. AB - Two hundred and fifty-three multiple myeloma patients (136 males and 117 females; mean age 66 years) classified by the clinical criteria of Durie and Salmon underwent skeletal radiography; 148 of them had total body bone scintigraphy, and 130 bone marrow scintigraphy. A selected group of them (18 patients, both males and females) had densitometric bone examination, employing both quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). The results can be summarized as follows: 29.7% of patients exhibited no skeletal abnormalities at early staging. Spine (49%), skull (35%), pelvis (34%), ribs (33%), humeri (22%), femora (13%), and mandible (10%) were the most frequently involved locations. The main pattern is osteolysis as a characteristic "punched out" multiple lesion (43.3%), but the most frequent lesion is osteopenia (43.9%), particularly evident in the spine; pathologic fractures (54%) are seen in the ribs, vertebral bodies, limbs; typical radiographic associations of features and sites are observed, which sometimes make diagnosis easier. Total body scintigraphy, revealing aspecific uptake only in the presence of pathologic fractures, is not recommended in the first staging of the disease, but it is considered as an important technique in the follow-up, when the patients become symptomatic. Bone marrow scintigraphy, especially in the "marrow expansion" pattern, might be considered as a form of compensating attempt to recover the lost central space, destroyed by myelomatous involvement, of which it defines the pathologic and prognostic status. Bone densitometry, as it confirms the grade of osteopenia, reveals that osteoporosis is a peculiar characteristic pattern of bone disease in multiple myeloma, not only due to age. Conventional skeletal radiography is the main support in the diagnosis of lytic areas of multiple myeloma, and it remains--today--irreplaceable. The other diagnostic techniques (i.e., CT and MRI) may be used to detect the extent of bone and soft tissue involvement, in areas of complicated anatomy, and to define the degree of marrow involvement. PMID- 8493373 TI - [Chronic cor pulmonale in obstructive lung disease. Diagnostic evaluation with Doppler echography and other non-invasive imaging techniques]. PMID- 8493374 TI - [Optimization of the combination of techniques with ionizing electromagnetic radiations of different physical types, electrons, and heavy particles]. PMID- 8493375 TI - [Loco-regional intra-arterial chemotherapy combined with radiotherapy in cervical carcinoma]. AB - Fifteen patients with squamous cell carcinoma of the uterine cervix--7 in stage II, 6 in stage III and 2 in stage IV--were considered not to respond at the end of radiotherapy. Therefore, the whole patient population underwent bilateral intraarterial chemotherapy with Mitomycin-C (3 cycles, 3-4 weeks' intervals). Patients' responses were evaluated with clinical and CT examinations following irradiation and after completing chemotherapy. Pelvic irradiation was administered by external beams (6 Mv), for a 50-Gy dosage (200 cGy/day for 5 weeks); in 4 cases treatment was completed by means of brachytherapy (192 Ir), with 20-25 Gy dosage. Intraarterial infusion was carried out after positioning the catheters in both uterine arteries; in 5 cases, the internal iliac artery alone was cannulated. At the end of the combined treatment, 2 patients (13%) responded completely, 9 (60%) partially and 4 (27%) not at all. Mean survival was 24 months. No hematologic complication was so severe that treatment had to be discontinued. In 4 patients chemotherapy caused a partially ulcerated skin erythema in the buttocks, which was completely cured in all cases. PMID- 8493376 TI - [Preoperative localization and anchoring of pulmonary nodules under computed tomography guidance]. AB - Videoendoscopic thoracic surgery is often employed to remove peripheral lung nodules. Since manual palpation is excluded, the authors obviate the difficulty of intraoperative nodule localization by employing a thin snap open mandrel under CT to guidance localize, fix and anchor the nodule. Traction can be exerted on the device allowing for rapid nodule identification and facilitating wedge resection removal. This technical innovation, as yet applied only to a limited number of cases, widens the indications of videothoracoscopic surgery and appears complication-free. PMID- 8493377 TI - [A new catheter for enteroclysis: Torino 1. Results in 398 cases]. AB - The authors report on the use a new barium enema catheter employed in 398 patients from January, 1990 through June, 1991. Its innovative characteristics and several possible uses are compared with those of conventional equipment. Particularly, the advantages offered by the various possible placement sites of the catheter--i.e., the II duodenal portion and beyond the ligament of Treitx- are discussed, together with its different uses according to clinical symptoms: its best location is beyond the ligament of Treitz in subocclusions, versus in the II duodenal portion if tumors or other duodenal conditions are suspected. The new catheter exhibited 100% accuracy; the average exposure time for radioscopy during its positioning was 3 minutes. A selected group of 149 patients was examined for complications, which were few (8%), of poor importance, short and completely curable. PMID- 8493378 TI - [Bilateral congenital mucocele of the lacrimal sac with intranasal spread]. PMID- 8493379 TI - [Aseptic bone necrosis associated with amyloidosis of the femur head after renal transplantation. Description of 2 cases]. PMID- 8493380 TI - [A case of osteochondritis of the first metatarsal head diagnosed with computed tomography]. PMID- 8493381 TI - [Pseudoaneurysm of the femoral artery after angiographic procedures. Non-surgical treatment with ultrasonography-guided compression]. PMID- 8493382 TI - [Neoplasm of the ampullar region of the duodenum. Considerations on 2 cases diagnosed with ultrasonography]. PMID- 8493383 TI - [Non-Hodgkin's lymphoma with primary perirenal location. Description of a case]. PMID- 8493384 TI - [A case of bladder hernia associated with ovarian myxoma]. PMID- 8493385 TI - [Ovarian varicocele treated with percutaneous scleroembolization. Description of a case]. PMID- 8493386 TI - [Liposarcoma of the spermatic cord. Description of a case]. PMID- 8493387 TI - [Role of intraoperative brachytherapy in the treatment of lymph node recurrence of rhinopharyngeal carcinoma. Report of a case]. PMID- 8493388 TI - A population-based case-control study of cancer of the bile ducts and gallbladder in Quebec, Canada. AB - In a population-based case-control study of pancreatic cancer in Greater Montreal between 1984 and 1988, a total of 24 patients with cancer of the bile ducts and 33 patients suffering from cancer of the gallbladder were compared to 239 population-based controls. This study was part of the SEARCH program of the International Agency for Research on Cancer. In cases of cancer of the bile ducts, smoking nonfiltered cigarettes produced a relative risk of 2.82 and a 95% confidence interval of 1.01-7.86 after adjustment for age, sex, other smoking habits, alcohol consumption, schooling, and respondent status. Laxative intake was associated with a risk of 2.87 (1.00-8.22). Coffee drinkers were collectively at lower risk than non-drinkers: OR = 0.26 (0.07-0.95). In patients with cancer of the gallbladder, constipation was related to a risk of 3.19 (1.02-9.95) after adjustment for the same factors. In cases with previous gallbladder problems, the risk was found to be significant [OR = 7.96 (2.03-31.2)], 8 times greater in cases than in controls. PMID- 8493389 TI - Trends in biliary tract cancer. AB - Incidence data from a large number of cancer registries throughout the world are presented for cancers at various sub-sites of the biliary tract, to assess whether the epidemiology of gall bladder cancer can be distinguished from cancer of the extra-hepatic bile ducts and cancer of the ampulla of Vater. Cancers of the biliary tract appear to be strongly sex-related. A marked genetic susceptibility emerges from this review, not only for gall bladder cancer, as previously reported for American Indians, but also perhaps for cancer of the extrahepatic bile ducts, for which Japanese of both sexes have high rates. Mortality data for all biliary tract (mainly gall bladder) cancer are examined for the period 1958-85. A wide range of trends is observed, notably a consistent decline in mortality among Anglo-Saxon populations, for both males and females. Dietary factors, possibly mediated through hormonal and genetic factors, are suggested as a major causal influence on biliary tract cancers. PMID- 8493390 TI - Non-invasive diagnosis of liver cirrhosis: a comparison between four discriminant functions. AB - We assessed the performance of 4 methods of discriminant analysis using as independent variables the age and 16 serum tests, for correctly identifying patients with liver cirrhosis among hospitalized patients affected by chronic liver disease without signs of liver failure; 290 patients entered this study: on the basis of laparoscopy with or without liver biopsy, 152 patients had a diagnosis of liver cirrhosis and 138 were classified as chronic hepatitic patients. Due to the non-multinormal distribution of the variables used and to the unequality of the variance-covariance matrices, we compared the following 4 methods: linear discriminant function, quadratic discriminant function, non parametric discriminant function and logistic regression. The Receiver Operating Characteristic (ROC) analysis was used to compare diagnostic ability of the assessed methods: the quadratic discriminant function was the best performing method. The predictive ability of this function was compared to that reported for percutaneous liver biopsy, showing that this simple statistical method using age and biochemical tests can efficiently identify liver cirrhosis in the setting of chronic liver disease, reducing the need for invasive diagnostic procedures. PMID- 8493391 TI - [Value of nutritional indicators for the prognosis of intrahospital mortality in children in Kivu]. AB - From 1986 to 1988, 1,129 children were hospitalized in Lwiro (South-Kivu, Zaire) 3/4 of which were severely malnourished. Anthropometric, clinical and biological indicators were measured at admission. Observed mortality rate was 17.4%. Survival curves differ significantly for each anthropometric parameter measured at inclusion. In multivariate analysis, weight for age calculated with local reference or arm circumference is significantly associated with survival. The addition of serum albumin concentration to the multivariate model, shows this variable to be important. However, the use of an anthropometric indicator, such as weight for age or arm circumference is still important because it maintains an independent and significant effect on survival. PMID- 8493392 TI - [Prevalence of dementia in Gironde (France)]. AB - The objective of the study is to estimate the prevalence of dementia using the data of the Paquid cohort. A sample of 3,149 subjects aged 65 years and older living at home or in institution was randomly chosen in Gironde (France). A questionnaire and psychometric tests were used to evaluate cognitive functioning and the presence of dementia was assessed through DSM III Diagnostic and Statistical Manual of mental disorders (ed. III) criteria. Hachinski scale and work group NINCDS-ADRDA criteria were applied to confirm the presence of dementia and identify Alzheimer's disease. Overall prevalence was estimated to 4.3%. No difference was found between men and women. The prevalence increased with age with nearly a doubling every 5 years of age. In institution, dementia frequency remained stable. The relative risk of a demented subject to be institutionalized with regard to a non demented subject decreased with age. PMID- 8493393 TI - [Mortality due to suicide in prison]. AB - Previous studies identified correlations between suicide in prison and socio demographic and crime characteristics. However links between these variables were not taken into account. In this paper we use a regression model to the study of the determinants of suicide in prison in order to isolate the individual effect of each variable. We confirmed previous observations such as the increase in suicides with the increase in length of imprisonment. The sex of the individual and the nature of the crime did not correlate with suicide rate. The major risk factors for suicide were high social status and a high degree of social and family integration. These results contrast with observations on suicide outside the prison environment, for which the contrary was found. PMID- 8493394 TI - Conditions of validation and use of the screening method for vaccine efficacy evaluation. AB - If PV is the proportion of the target population vaccinated and PCV the proportion of cases in the same population who have been previously vaccinated, vaccine efficacy can be computed as (PV-PCV)/[PV(1-PCV)]. In the screening method, this formula is currently applied to sample values. The objective of this paper is to provide the corresponding statistical tools. Taylor series expansion has been used to derive the bias, variance and confidence interval of the estimate. The bias may be very high when vaccine efficacies are low. It is below 1% for vaccine efficacies higher than 80%. Monte Carlo simulations were used to assess the departure from normality of the estimate. The number of subjects required by the method for given precisions are presented. PMID- 8493395 TI - [Evaluation and utilization patterns of antibiotic therapy. A study in 4 hospital departments]. AB - The use of antibiotics in 480 cases in 4 hospital wards during 1988 was assessed by examination of medical records. Only the first antibiotic therapy administered during the first stay in the ward for each patient was included. Antibiotics were administered to 163 in-patients (37% of hospitalizations) for infections in 113 (26%) cases. Amoxycillin and macrolides were the drugs most frequently used. Sixty-eight percent of the treatments were administered in the absence of microbiological data. Single drug therapy was used in 60% of treatments. Fifty in patients (11% overall; 41% of patients undergoing surgery) received antibiotics for prophylaxis. The exact indication(s) for the choice of therapy was not given in the medical records of 39% of cases. Treatment started within 48 hours of infection in 15% of the cases. Overall, 93% of the treatments given were indicated, but 53% were inappropriate because they were too expensive, unlikely to be effective or were multiple drug therapy without justification. There are a variety of factors that cause such inappropriate administration of antibiotics. PMID- 8493396 TI - [Smoking among students of the CM2) (2d-year intermediate course): evaluation of knowledge and behavior]. AB - This paper reports the results of a survey conducted on smoking among 1490 eleven years old schoolchildren. They answered to an individual questionnaire before and after they had been informed on smoking by school doctors. In this age group, 26.2% of the children have already had some contact with cigarette, and 0.5% smoke regularly. The household smoking habits have an important influence on the attitude of children toward smoking. Knowledges on smoking dangers have been evaluated before and after information. This survey shows the importance of smoking prevention, especially among young children. PMID- 8493397 TI - [Internal validation of a measurement scale: relation between principal component analysis, Cronbach's alpha coefficient and intra-class correlation coefficient]. AB - The objective is to establish a simple relationship between two frequently used validation techniques which have been developed in the literature along the same lines: Principal Component Analysis and Cronbach's alpha. We have shown that under certain conditions, it is possible to estimate the reliability by using the results of a Principal Component Analysis only. Moreover, we report the relation between Cronbach's alpha and intraclass correlation coefficient, which are both used to estimate the reliability of continuous measures. PMID- 8493398 TI - [Estimate of vaccine coverage of children in the last year public primary school in Paris in 1990-1991]. PMID- 8493399 TI - [Current definitions of AIDS in the United States and Europe]. PMID- 8493400 TI - ATP-MgCl2 pre-treatment in an animal model of asphyxial arrest. AB - ATP-MgCl2 treatment has been found to be a promising intervention in many models of hypoxic/ischemic injury. In this study, the effect of pre-treatment with ATP MgCl2 on the hemodynamic response to asphyxia in the rat was examined. Rats were anesthetized with halothane and N2O2. A tracheostomy and femoral artery and vein cutdowns were performed. Rats were infused intravenously with either ATP-MgCl2 (approximately 50 mumol/kg) or normal saline (control group) over 15 min. Animals were then asphyxiated for 8 min by occlusion of the ventilator tubing. Following the asphyxia, 1 min of cardiopulmonary resuscitation (CPR) was attempted. Heart rate and blood pressure were monitored continuously throughout the experiment. A total of 41 animals (21 ATP-MgCl2, 20 control) were studied. Analysis of variance (ANOVA) was used to test for differences between groups. The ATP-MgCl2 group had a lower heart rate (HR) and mean arterial pressure (MAP) during the infusion. During asphyxia the ATP-MgCl2 group had a lower MAP but higher HR when compared to the control group. No significant differences were observed in the rates of successful resuscitation between ATP-MgCl2-treated rats (10 of 21, 48%) and controls (12 of 20, 60%). Possible reasons for the apparent lack of benefit of ATP-MgCl2 therapy are discussed. PMID- 8493401 TI - Visceral, hematologic and bacteriologic changes and neurologic outcome after cardiac arrest in dogs. The visceral post-resuscitation syndrome. AB - We studied the post-resuscitation syndrome in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We reported previously, in the same dogs, no difference in resuscitability, mortality, or neurologic outcome between the three insult groups. There was no pulmonary dysfunction, but post-arrest cardiovascular failure, of greater severity in the 12.5 min arrest group. This report concerns renal, hematologic, hepatic and bacteriologic changes. Renal function recovered within 1 h after arrest, without permanent dysfunction. Clotting derangements at 1-24 h postarrest reflect transient disseminated intravascular coagulation with hypocoagulability, more severe after longer arrests, which resolved by 24 h after arrest. Hepatic dysfunction was transient but more severe in the animals that did not recover consciousness and correlated with neurologic dysfunction, but not with brain histologic damage. Bacteremia was present in all animals postarrest. We conclude that in the previously healthy organism after cardiac arrest of 7.5-12.5 min no flow, visceral and hematologic changes, although transient, can retard neurologic recovery. PMID- 8493402 TI - Detoxification with hemabsorption after cardiac arrest does not improve neurologic recovery. Review and outcome study in dogs. AB - We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated. PMID- 8493403 TI - Studies of the protein synthesis system in the brain cortex during global ischemia and reperfusion. AB - Previous studies have demonstrated that brain protein synthesis declines after global ischemia and reperfusion. To investigate the role of the translation system in this phenomenon, we examined the ability of partially purified ribosomes, ribosome-bound mRNA and translation cofactors derived from the transiently ischemic cerebral cortex to synthesize protein in vitro. Samples were prepared from canines subjected to 20-min cardiac arrest and after 2 or 8 h of post-resuscitation intensive care. There was no significant decrease in the rate of in vitro protein synthesis as a consequence of either ischemia or reperfusion. Northern hybridization of ribosome-bound RNA revealed a discrete band of mRNA for brain-specific creatine kinase (ck-bb) that was consistent in presence and intensity in all groups. However, mRNA for heat shock 70 protein (hsp-70) was observed only during reperfusion and markedly increased between 2 and 8 h reperfusion. Thus, we conclude that (1) the transcription system is intact during reperfusion and hsp-70 mRNA is made and translocated to the ribosomes during reperfusion, (2) mRNA for ck-bb is not displaced from ribosomes by the appearance of hsp-70 during reperfusion and (3) isolated ribosomes maintain their ability to translate in vitro during the first 8 h of reperfusion after global brain ischemia. Therefore, the early reduction in protein synthesis observed in vivo during post-ischemic brain reperfusion is not due to an intrinsic dysfunction of the ribosomes. PMID- 8493404 TI - Cardiac arrest: prognostic factors and outcome at one year. AB - This study was designed to determine by multivariate statistical methods the influence of 38 variables on outcome after cardiopulmonary resuscitation (CPR) and to assess neuropsychological status in long-term survivors. The charts of 181 consecutive patients resuscitated in a 1,100-bed University Hospital over a 2 year period were analyzed retrospectively. Of the 181 resuscitated patients, 23 (13%) could be discharged. Outcome was significantly affected by the following variables: presence of shock or renal failure before cardiac arrest (CA) (odds ratio = 10.6; 95% confidence interval = 1.3-85.8 and odds ratio = 13.8; 95% confidence interval = 1.7-109.2, respectively), administration of epinephrine (odds ratio = 11.2; 95% confidence interval = 3.2-39.2) or prolonged CPR (> 15 min) (odds ratio = 4.9; 95% confidence interval = 1.7-13.7). By contrast, when CA occurred in uncomplicated acute myocardial infarction a significantly better prognosis could be demonstrated (odds ratio = 0.2; 95% confidence interval = 0.0 0.6). The 10 long-term survivors investigated lead an independent life and all returned to former occupation. The most common complaint was moderate memory disturbance (five patients). The conclusion is that this study confirms the critical influence of cellular anoxia on prognosis and allows the improved delineation of the situations in which cardiopulmonary resuscitation appears to be hopeless or likely to be successful. The follow up in a small number of survivors has shown a good quality of life and minor neuropsychological sequellae. PMID- 8493405 TI - Fifteen minutes and cardiac arrest. PMID- 8493406 TI - Death, dying and revival: ethical aspects. PMID- 8493407 TI - The relationship between quality assessment and research methods. PMID- 8493408 TI - Medical audit--the APO-method in general practice. PMID- 8493409 TI - The role of patient satisfaction assessment in medical audit. PMID- 8493410 TI - Medical audit and patient satisfaction surveys. PMID- 8493411 TI - Standards of care or standard care? Guidelines in general practice. PMID- 8493412 TI - Is variation a quality in general practice? PMID- 8493413 TI - The measurement of needs and outcomes: aids to enhancing shared understanding between doctors and patients? PMID- 8493414 TI - Coupling of perspectives in quality assessment. PMID- 8493415 TI - Qualitative methods in quality assessment of doctor-patient meetings in general practice. PMID- 8493416 TI - Episode-oriented data and quality assessment. PMID- 8493417 TI - Workshop--methods of quality assessment in general practice. PMID- 8493418 TI - Computer-based longitudinal recording of episodes of care in general practice using the International Classification of Primary Care (ICPC). Experience from one practice. Perspectives for audit and quality assessment. PMID- 8493419 TI - Survey of ongoing activities of quality assessment in general practice in Denmark. PMID- 8493420 TI - Behind closed doors: the data monitoring board in randomized clinical trials. AB - Many randomized clinical trials include a data and safety monitoring board (DSMB) that is responsible for reviewing accruing data, monitoring performance of the trial, assuring safety of the participants in the trial, and assessing the efficacy of treatment. The DSMB often makes recommendations about continuation of the trial or alteration of the protocol. Although such boards are very influential in both the conduct and interpretation of randomized clinical trials, there is no standard mode in which DSMBs operate nor do they routinely report publicly about their deliberations. This paper describes the composition of DSMBs as well as their functions. It concludes with a series of questions that needs to be addressed to ensure that the DSMBs operate effectively. PMID- 8493421 TI - The NHLBI model: a 25 year history. AB - Although newer techniques and procedures have been developed, many of the clinical trial design and monitoring concepts used today in the NHLBI were implemented 25 years ago. Among these are the organizational structure of multicentre trials and the use of an independent data monitoring committee. Examples of data monitoring committee discussions and decisions are provided. PMID- 8493422 TI - A survey of monitoring practices in cancer clinical trials. AB - This paper reports the results of a survey of data monitoring practices of the 12 clinical co-operative groups in cancer sponsored by the National Cancer Institute in the United States. Most of these co-operative groups conduct a large number of active clinical trials in a wide variety of cancers. The number of active phase III trials in 1991 was 244 with nearly 24,000 patients entered on these trials. The survey instrument used in this paper was modified from one originally developed by Geller and Stylianou, supplemented by questions on the responsibilities of data monitoring committees based on Hawkins. Topics covered included general policies and procedures on the monitoring of clinical trials in these groups as well as specific questions on the responsibilities and operational procedures of formal data monitoring committees. Although formal statistical stopping rules are almost always employed in cancer trials in these co-operative groups, use of a formal data monitoring committee is a relatively new, but increasing practice. For a variety of economic and practical reasons, the members of data monitoring committees for cancer trials are rarely independent of the study participants. PMID- 8493423 TI - Data monitoring committees for Southwest Oncology Group clinical trials. AB - A monitoring committee policy was established by the Southwest Oncology Group in 1985 to address documented problems in study conduct. Committees consisting of the study coordinators, disease committee chair, study statistician, Group chair, Group statistician, an uninvolved Southwest Oncology Group clinician, an NCI representative, and a representative from each involved group for intergroup studies have been appointed for each phase III study. Business is conducted largely through the mail and through conference calls. Since then, problems identified in older studies have been largely resolved. Appropriate and timely decisions are being made at modest additional expense to the Group. PMID- 8493424 TI - The use of external monitoring committees in clinical trials of the National Institute of Allergy and Infectious Diseases. AB - Randomized clinical trials are being conducted and/or sponsored by all scientific divisions of the National Institute of Allergy and Infectious Diseases (NIAID). External committees to review the progress of ongoing trials and to make recommendations to the Institute concerning continuation or termination are an integral part of many of these trials. These committees have evolved considerably from the ad hoc committees, called together when a need arose, which were used beginning in the mid 1970s. Currently, there are many monitoring committees operating for NIAID-sponsored trials. They function in a variety of ways, based partially on historical precedent and partially on the specialized requirements of the particular trial; there is no 'standard operating procedure' for the Institute, or even for divisions within the Institute. One of the major issues faced in establishing the data and safety monitoring board for AIDS treatment trials was access to the meetings of this board and to the reports of interim data that the board reviewed. After much discussion, procedures were established that restrict such access to a very limited group of programme and statistical centre staff. These procedures, while remaining controversial, appear necessary to ensure confidentiality and the integrity of the clinical trials process. PMID- 8493425 TI - Data monitoring and interim analyses in the pharmaceutical industry: ethical and logistical considerations. AB - The characteristics of data monitoring and the need for the use of data monitoring committees in clinical trials sponsored by the pharmaceutical industry differ from those of trials sponsored by government. Data monitoring is a continuous process in industry trials due to the regulatory requirements and the need to more thoroughly evaluate safety of new compounds. As part of this process, interim analyses are employed to make decisions about treatment effects. In some cases, such analyses may require the use of an external data monitoring committee to assist in the data review, analysis and decision making. A number of examples of interim analyses, with and without data monitoring committees, are discussed. Issues surrounding the need for external data monitoring committees and recommendations are presented. In particular the issues of sponsor participation in the data monitoring committee and controls of the decision making process are considered. PMID- 8493426 TI - Monitoring of clinical trials and interim analyses from a drug sponsor's point of view. AB - This paper illustrates aspects of data monitoring of clinical trials in the pharmaceutical industry. Formal interim analyses are performed at least in part to address the question of whether the trial should proceed or whether there should be an early termination of the trial. For formal interim analyses, frequently independent data and safety monitoring committees are utilized for monitoring clinical trials, and adjustments to nominal significance levels for test statistics are required. Various statistical methods developed during the last fifteen years are utilized. Administrative interim analyses are those analyses that are performed without any intention to stop the trial as a consequence of those analyses. For administrative interim analyses, adjustments to significance levels may not be required, but results must still be carefully interpreted. Regardless of the interim analyses performed, it is critical that the plans for interim analyses be identified in the study protocol, and the dissemination of interim results be carefully restricted. The following clinical trials sponsored by Merck Sharp and Dohme Research Laboratories (MSDRL) will illustrate these points: CONSENSUS; CONSENSUS II; 4S; Haemophilus influenza type b efficacy trial; famotidine in upper gastrointestinal haemorrhage, and a phase II analgesic study. It is anticipated that data monitoring and interim analysis activities will increase for future clinical trials due to the availability of appropriate statistical methods and improved data management systems. PMID- 8493427 TI - Monitoring clinical trials: experience of, and proposals under consideration by, the Cancer Therapy Committee of the British Medical Research Council. AB - The accumulating data from all randomized trials conducted by the Cancer Therapy Committee (CTC) of the British Medical Research Council are monitored on a regular basis. However, for important practical reasons the form of this data monitoring may vary from trial to trial. Thus a trial addressing what is considered a major question in the treatment of cancer patients, (a 'pivotal' or 'high profile' trial), has a formal data monitoring committee (DMC). This is usually made up of two clinicians and one statistician who are completely independent of the trial organization and do not enter patients into the trial. Other trials, which constitute the majority, are monitored by a less formal trial progress group made up of the clinical co-ordinator and trial statistician, sometimes supplemented by a trial participant. Experience with this dual system has led to a new proposal: if the trial progress group wish to modify or stop a trial then they are required to set up and consult an ad hoc DMC for independent advice. This proposal has many advantages, including maximizing the use of resources available, while achieving the degree of objectivity in decision-making required for the many different types of cancer trials conducted by the CTC. PMID- 8493428 TI - The use of data monitoring committees in Canadian trial groups. AB - Following a brief overview of the funding and structure of clinical trials research in Canada, experience with data monitoring committees (DMCs) in four clinical trials organizations is reviewed. Whether committees are required, their mode of selection, composition, degree of independence, mandate and reporting relationships have varied substantially among the groups. Overall the Canadian experience with DMCs has been representative, although formalization of the role of these committees has not proceeded as far as it has in some US agencies. PMID- 8493429 TI - Interim analyses, stopping rules and data monitoring in clinical trials in Europe. AB - A survey was carried out to identify the current policies of European cooperative groups with respect to interim analyses, stopping rules and data monitoring of ongoing clinical trials. The policies differ widely, from informal interim analyses distributed among all participating investigators, to planned interim analyses carried out by an independent statistician and scrutinized by a data monitoring committee. Different situations clearly call for different policies: for instance, trials of new drugs in AIDS need to be monitored more closely than trials of non-toxic adjuvant therapies for cancer. Likewise, trials with an immediately measurable end-point (such as the large-scale trials in myocardial infarction) need more intensive monitoring than those in which the outcome assessment requires prolonged follow-up. In all cases, however, it seems useful to articulate explicit data monitoring procedures in the trial protocol. In general, an independent data monitoring committee is essential to advise on the desirability to continue accrual into the trial, or to stop it early. PMID- 8493430 TI - Practical issues in data monitoring of clinical trials: summary of responses to a questionnaire at NIH. AB - A targeted poll was undertaken to compare and contrast models of data monitoring of randomized clinical trials sponsored by the National Institutes of Health. In an attempt to represent the institutes which conduct clinical trials, twelve individuals were selected and asked to respond to a questionnaire specifically prepared for this workshop. The response rate was 100 per cent. Most of the large trials sponsored by the institutes have independent, formally constituted data monitoring committees. There was one institute which does not have any data monitoring committees. The questionnaire is described in detail and a summary of the results is given. PMID- 8493431 TI - Data monitoring boards in the pharmaceutical industry. AB - This paper describes the characteristics and responsibilities of data monitoring boards (DMBs) employed in clinical trials sponsored by pharmaceutical firms. These DMBs are compared with DMBs in clinical trials sponsored by the National Institutes of Health (NIH). All trials discussed are assumed to be phase III pre market clinical trials. It is seen that DMBs in pharmaceutical industry trials have more limited responsibilities than DMBs in NIH clinical trials. Pharmaceutical industry DMBs are employed to add credibility to trials by certifying critical clinical trial processes such as patient evaluability, interim analyses, evaluation of efficacy endpoints, and safety monitoring. An example of a pharmaceutical industry DMB's charter and operations is presented for a clinical trial for the prevention of stress ulcers. The specific problems encountered when a pharmaceutical industry clinical trial is conducted by NIH under the auspices of an NIH-appointed DMB are discussed. New uses for DMBs in the pharmaceutical industry are introduced and future trends in the industry with respect to DMBs are examined. PMID- 8493432 TI - Data monitoring committees and capturing relevant information of high quality. AB - The integrity and credibility of randomized clinical trials, designed to provide a definitive evaluation of therapeutic interventions, can be substantially enhanced if periodic review of results on the relative efficacy of treatments is conducted by a data monitoring committee (DMC). The role of the DMC can include some important activities which promote obtaining relevant information of high quality. In the final stage of study development, these include review of protocol-specified study objectives and design, and review of procedures planned for capturing high-quality data and for reporting to the DMC. At analyses during the trial, these include careful review of data completeness and accuracy to assist in early detection and resolution of evolving problems. PMID- 8493433 TI - Data monitoring committees: the moral case for maximum feasible independence. AB - Since data monitoring committees (DMCs) began to be established in the 1970s, they have reviewed the clinical outcome data emerging from ongoing trials. The thesis of this essay is that DMCs most effectively promote the validity and credibility of randomized clinical trials when they perform this function with the maximum feasible independence. The essay argues that four types of individuals and groups should be excluded from the interim monitoring of outcome data: (1) investigators entering patients into a trial; (2) principal investigators or study chairs; (3) representatives of commercial firms connected with a trial; and (4) representatives of regulatory agencies. The role of statistical groups and officials of government funding agencies in the review of outcome data is also discussed. PMID- 8493434 TI - Some FDA perspectives on data monitoring in clinical trials in drug development. AB - The FDA's interest in data monitoring of clinical trials derives from its public health responsibility to assure the safety and efficacy of new drugs based on evidence from adequate and well-controlled studies. Therefore the FDA is concerned that clinical trials of new drugs are designed and carried out in a manner that will insure the integrity and validity of study inferences. The FDA regulation and guidelines recognize the role of data monitoring and the variety and diversity of situations utilizing a data monitoring process in clinical studies. This paper describes relevant aspects of the regulations and guidelines, some concerns the FDA has with regard to monitoring of both government- and industry-sponsored trials and the consequences of early termination of trials of new drugs in the investigational and marketed stages. Comments include advice on communication between the FDA and data monitoring committees. PMID- 8493435 TI - [What is your roentgen diagnosis? Subtotal stenosing tumor of a proximal jejunum loop (lymphoma)]. PMID- 8493436 TI - [Chronic viral hepatitis: current diagnosis and therapy]. AB - Viral infections are major causes of chronic liver diseases. The etiologic agents are hepatitis B virus (HBV), the HBV-associated hepatitis delta virus (HDV) and hepatitis C (HCV). In general, these viral infections can be specifically identified by serological tests and molecular techniques. The identification of the causative agents is clinically relevant both for epidemiologic-preventive and therapeutic considerations. The therapy of choice for chronic viral hepatitis B or C is interferon-alfa (10 mill units 3x per week for about 6 months). The long term response rate is 30 to 40% for chronic hepatitis B and 20 to 30% for chronic hepatitis C. The results for chronic hepatitis D are controversial at present. Based on these results, therapeutic strategies have to be modified and improved further. Apart from therapeutic considerations, measures to prevent viral hepatitides should be carefully implemented (HBV vaccination of individuals at risk, reduction of blood transfusions, general hygienic measures), in order to reduce the morbidity and mortality from acute and chronic hepatitis, including liver cirrhosis and hepatocellular carcinoma. PMID- 8493437 TI - [Therapy of hyperlipoproteinemia]. AB - Triglycerides and cholesteryl esters are non-polar molecules and, therefore, insoluble in aqueous fluids such as blood. Lipid transport in blood is only possible the formation of lipoproteins. This article proposes a concept for the treatment of hyperlipidemias that is based on lipoprotein pathology. The liver secretes the triglycerides and cholesteryl esters in the form of very-low-density lipoproteins (VLDL). Lipolysis hydrolyzes VLDL triglycerides, providing tissues with fatty acids. and gives rise to relatively cholesterol-enriched intermediate density lipo- proteins (IDL) and low-density lipoproteins (LDL). IDL and LDL are removed from plasma by receptor-mediated cellular uptake. An increased plasma concentration of VLDL ensues in predominant hypertriglyceridemia (e.g. triglycerides 9 mmol/l, cholesterol 7 mmol/l). VLDL are not considered to be directly atherogenic, but increased levels of VLDL often occur together with an atherogenic decrease of high-density lipoproteins (HDL). Elevated VLDL levels respond well to dietary measures; fibric acid derivatives, nicotinic acid and omega-3-fatty acids also effectively lower VLDL. An increase in IDL leads to both hypertriglyceridemia (e.g. 3 mmol/l) and hypercholesterolemia (e.g. 7 mmol/l). IDL are considered directly atherogenic. Hyperlipidemias due to IDL respond to the same interventions as those due to VLDL. An increased blood level of LDL leads to hypercholesterolemia (e.g. 7 mmol/l) with normal triglyceride levels (e.g. 1 mmol/l); LDL are considered directly atherogenic. Dietary measures can reduce LDL levels by about 10%, but pharmacological treatment by inhibitors of cholesterol synthesis ('statins') and by ion exchange resins is much more effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493438 TI - [Current drug problems]. AB - From the multifaceted and complex catalog of problems in drug abuse those are selected that are relevant for medical practise. After a short introduction the situation of drug abuse in the canton of Zurich is described, based on estimates about users, descriptions of consumed amounts, market prices of heroine and cocaine and a summary of some epidemiologic data and the sequelae of drug dependence. In a second part substitution by methadone is described in detail. In a third part cocaine with its effects and adverse effects is presented in more detail. PMID- 8493439 TI - [Lambarene 25 years after Albert Schweitzer]. AB - The author, who lived with Albert Schweitzer during the last four years of the doctor's life, and who worked as a physician in Lambarene for ten years, tells about the evolution of the Gabonese Republic and the Lambarene Hospital since 1961. The actual medical importance of the hospital as well as the spiritual response Schweitzer still finds today among Africans are described. And: Africa, too, has a message for us. PMID- 8493441 TI - [Sixth scientific workshop of the National Federation of the Colleges of Medical Gynecology. Rouen, January 8-9, 1993]. PMID- 8493440 TI - [Association of breast cancer and cancer of the uterus. 34 case reports]. AB - A retrospective series of 34 cases of breast cancer combined with uterine cancer is reported. Cancers of the endometrium differed from cervical cancers by their number, 2.2 x more frequent (22 vs 10) and by the sequence of onset: they generally precede breast cancer, whereas they tend to follow cervical cancers. In contrast to the breast cancer/uterine cervical cancer association, which is considered to be fortuitous, the breast cancer/cancer of the uterine body association appears to be determined by a hormonal context. Through a review of the literature, a unifying endocrine theory is constructed, based on the role of hyperestrogenesis in mammary and endometrial carcinogenesis. PMID- 8493442 TI - [The role of ultrasound-guided puncture in the evaluation of liquid tumors of the ovary]. AB - Twenty percent of liquid tumors of the ovary are persistent functional cysts. Laboratory tests of the cystic fluid should make it possible to distinguish between functional cysts and organic cysts. In 170 patients derived from a multicenter study and presenting with a liquid tumor of the ovary (including 9% of cancers), samples of the cystic fluid and serum were taken from the patient and the ACE, CA 125, CA 19-9 markers, estradiol and Progesterone were assayed. The results of these assays were subjected to computerized analysis and compared with the pathological findings. The assays were able to discriminate between organic cysts and functional cyst with 93% of sensitivity and 95% specificity. The insufficient reliability of this evaluation justified a second study (in progress) which is limited to the study of pure fluid tumors with thin walls, no partitions, no vegetations and measuring less than 8 cm in diameter in which the incidence of cancers is very low. This study should fine tune the initial findings and result in a sensitivity approaching 100 percent. If this hypothesis is confirmed, it should be possible to include ultrasound-guided puncture carried out under closely defined conditions in the therapeutic decision trees for liquid cysts of the ovary. PMID- 8493443 TI - [Non-surgical female sterilization using quinacrine: efficacy of two insertions of quinacrine pellets]. AB - In a group of 159 women at Santiago du Chili, fertility control by means of chemical occlusion of the utero-tubular junction was assessed. Two transcervical intra-uterine insertions of 216 mg of quinacrine, carried out at an interval of one month and associated with 50 mg of intra-uterine diclofenac and 150 mg of intra-muscular diclofenac resulted in a pregnancy rate after 12 months of 2.1 per 100 women and a Pearl index of 1.63 at 27 months after the sterilization process. The complications and adverse events appear to be similar to those which occur during insertion of an IUD and were minor and transient, disappearing within a few hours or at most 2 days after the procedure. PMID- 8493444 TI - [Tubal anastomosis by controlled scarring. Results]. PMID- 8493446 TI - [Positive diagnosis of Potter's syndrome by ultrasonography. A case report]. AB - Potter's syndrome is a rare disorder but on which should not be overlooked. Ultrasound signs such as oligoaminos, retarded intra-uterine growth. (R.I.U.G.) and failure to detect the bladder and kidneys constitute fairly clear signs. Early and specific diagnosis leads to therapeutic pregnancy termination. This allows the parents to avoid the painful and late birth of a malformed child. PMID- 8493445 TI - [Hormones and embryogenesis of the uterine cervix]. AB - In the absence of the T.D.F. gene, differentiation of the genital tract follows the female development with Wolffian ducts regression, elaboration of Mullerian ducts, and homologous uro-genital sinus organization. Up to week 32, the fetal ovary secretes no organizing substance and no estrogen. Even if the maternal body is heavily impregnated by estrogens from the fetal-placental unit, the estrogenic and progestogenic activity of any steroid hormones which cross the placental barrier and enter the fetal body is reduced as a result of metabolic degradation within the fetal liver. It is only from week 32 that in normal pregnancies, phenomena of estrogenic action on the uterine cervix of the fetus are seen. This consists of hyperplasia of the endo-cervical epithelium and its emergence towards the exo-cervix. The slightest addition of non-steroid synthetic estrogens administered to the mother may interfere with this hormonal environment of the fetus and result in abnormal development of Muller's tract, particularly in the cervico-vaginal zone. PMID- 8493447 TI - [Rupture of an unscarred uterus at full term after an intracervical application of dinoprostone (Prepidil) gel]. AB - The authors report a case of uterine rupture following intra-cervical application of dinoprostone (two doses at an interval of 6 hours). No oxytocic had been administered and recording of the contractions had revealed no hyperkinesia or hypertonia one hour before rupture occurred. PMID- 8493448 TI - Cytosolic levels of estrogen-regulated pS2 protein in breast cancer: correlation with tumor proliferative activity. AB - Using a new immunoradiometric assay, a total of 100 cytosols obtained from primary breast tumors were examined for content of pS2, an estrogen-regulated protein. In our series, the median pS2 value was 5 ng/mg protein cytosol which was used as the cut-off. pS2 content was not correlated with menopausal status, tumor size, nodal involvement or tumor proliferative activity expressed as labeling index (tritiated thymidine LI). A positive correlation was found between pS2 and estrogen (ER) and progesterone (PgR) hormone receptors. pS2 in association with ER and PgR seems to identify tumor subgroups with diverse hormone responsiveness. Moreover, in favorable and unfavorable prognostic subgroups, LI and pS2 further emphasize this prognostic diversity. PMID- 8493449 TI - Effects of androgens on proliferation and progesterone receptor levels in T47D human breast cancer cells. AB - The effects of estradiol (E2), dihydrotestosterone (DHT) and dehydro-3 epiandrosterone (DHEA) on proliferation and progesterone receptor induction were studied in a breast cancer cell line (T47D) expressing estrogen, androgen, and progesterone receptors. A significant enhancement of growth and progesterone receptor expression was observed after treatment with E2 and DHEA, which was antagonized by the antiestrogen tamoxifen and not altered by the antiandrogen flutamide, supporting the involvement of estrogen receptors. When cells were treated with either E2 or DHEA, transforming growth factor-alpha mRNA was induced. DHT treatment did not alter growth but was effective in stimulating androgen receptors and down-regulating progesterone receptors. PMID- 8493450 TI - Influence of different growth factors on a rat choriocarcinoma cell line. AB - The influence of epidermal growth factor, insulin-like growth factors I and II, insulin, transforming growth factor beta 1 and transferrin on the growth of a postgestational rat choriocarcinoma was examined by the MTT [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The cell line was cultured in RPMI 1640 medium supplemented with fetal calf serum, beta mercaptoethanol, glucose, sodium pyruvate and antibiotics. The experiments were done in media supplemented with 10% (optimal) or 3% (suboptimal) fetal calf serum. Among the different growth factors tested, only epidermal growth factor and to a certain extent insulin had a growth-promoting effect by themselves. The other growth factors had either an additive effect in the presence of epidermal growth factor or no effect at all. The cytotrophoblast cells expressed both epidermal growth factor and transferrin receptors whereas the more differentiated giant cells expressed only transferrin receptors. PMID- 8493451 TI - Circulating markers and growth factors as prognosticators in men with advanced tongue cancer. AB - A retrospective study was performed on 52 advanced tongue cancer patients (stages III + IV) in order to assess the prognostic value of circulating prolactin, tissue polypeptide-specific antigen (TPS), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). These markers were correlated with short-term prognosis (2 years). The advanced tongue cancer patients had significantly elevated levels of prolactin (p < 0.02), TPS (p < 0.05) and EGF (p < 0.01) and low levels of IGF-1 when compared to controls. The patients were grouped according to the commonly used cut-off levels of these markers. A significant difference in survival was observed only between two subgroups of prolactin (< 15.0 and > 15.0 ng/ml; p < 0.001). Hence, prolactin may provide an independent predictor of short-term prognosis in patients with advanced tongue cancer. PMID- 8493452 TI - Effects of 17 beta-estradiol, progesterone and tamoxifen on in vitro proliferation of human pituitary adenomas: correlation with specific cellular receptors. AB - Six human pituitary adenoma cultures, characterized for estrogen and progesterone (Pg) receptors, were treated with 17 beta-estradiol (17 beta-E2), Pg and tamoxifen (TAM) at different concentrations, alone and in combination, for 2, 4 and 8 days. Cell proliferation data showed in most cases a stimulating effect of 17 beta-E2 and an inhibitory effect of Pg on cell growth, which appeared to be correlated with specific receptor expression, but independent of pituitary cell hormone content. A marked inhibitory effect of TAM on cell proliferation was present in all cases, but, on the contrary, was independent of estrogen receptor expression. PMID- 8493453 TI - Scavengers of oxygen-derived free radicals prolong survival in advanced colonic cancer. A new approach. AB - The influence of oxygen-derived free radicals on survival in advanced colonic cancer was assessed in a prospective randomized controlled double-blind trial using the radical scavengers dimethyl sulphoxide (DMSO) and allopurinol. Following palliative sigmoid colectomy for carcinoma at Dukes' stage D, 306 patients were randomized to the control group or to electrocoagulation of liver secondaries alone or with allopurinol (50 mg by mouth 4 times a day) or DMSO (500 mg by mouth 4 times a day). In 193 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p < 0.05) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals, suggest that these radicals mediate the detrimental effects of malignancy and that removing them incurs a survival advantage for patients with advanced colonic cancer. PMID- 8493454 TI - Erythrocyte rosetting in Plasmodium falciparum malaria--with special reference to the pathogenesis of cerebral malaria. AB - Spontaneous rosette formation of uninfected erythrocytes around an erythrocyte infected with Plasmodium falciparum is a recently described in vitro phenomenon which is also present in infections with some other malarial species where sequestration of parasite infected erythrocytes is a characteristic. In the present studies, rosetting was established as a P. falciparum virulence factor, the expression of which is modified by a variety of host factors, such as host immunity, ABO blood group and haemoglobin phenotype. The molecules involved in rosetting seem to be distinct from those involved in endothelial cytoadherence, although they are often co-expressed on the same parasitised red cell. Rosette formation was shown not only to be a phenomenon of laboratory-propagated strains, but also to exist in wild clinical isolates from all major malarious areas of the world. In two studies performed in The Gambia, comprising 211 children with uncomplicated or cerebral malaria, a strong association was found between in vitro rosette formation and cerebral malaria, indicating that rosetting plays a role in the pathogenesis of severe P. falciparum disease. Anti-rosetting activity, presumably mediated by antibodies, was found in sera from patients in malaria-endemic areas, and it was demonstrated that such activity was more abundant in individuals with uncomplicated malaria than in those with cerebral disease, suggesting that humoral immunity protects against rosette formation in vivo. It was also demonstrated, by the use of several independent assays, that erythrocytes from individuals with sickle-cell trait, alpha- and beta thalassaemia trait or with HbE, formed smaller and weaker rosettes than did normal (HbAA) red cells. The results also suggest that microcytosis per se is correlated to impaired rosette formation. Differences in rosetting ability were also seen between red cells of different ABO blood groups, with a diminished rosetting potential in blood group O red cells. Impaired rosette formation may thus contribute to the innate resistance to severe P. falciparum malaria that is known to exist in certain red cell disorders and in individuals of blood group O. Rosette formation was found to be governed by strong adhesive forces, with lectin like bindings between parasite-derived proteins exposed on the P. falciparum infected red cell surface, rosettins, and various carbohydrate moieties present on the uninfected erythrocyte. The strongest carbohydrate receptors seem to be contained within the blood group A or B antigens, and the rosettes were abolished by oligosaccharides mimicking these antigens. The binding between infected and uninfected erythrocytes was dependent on divalent cations and was sometimes sensitive to pH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8493455 TI - Testicular torsion: a follow-up study. AB - Thirty-five patients were examined 6-11 years after operation for torsion of the testis. Loss of testicular tissue was significantly associated with long preoperative duration of symptoms and with low postoperative sperm counts. The sex hormones were normal in the majority of patients but there were significantly higher levels of both FSH and LH in the group of patients with symptoms exceeding 8 hours. There was also a higher prevalence of abnormal semen quality in the same group. Furthermore, FSH and LH levels correlated significantly to the duration of symptoms and correlated inversely to the sperm count and concentration. Measurement of carnitine levels in seminal plasma, as a sign of vas deferens obstruction or dysfunction of epididymis, and of autoantibodies against spermatozoa revealed no significant findings. PMID- 8493456 TI - Lipid abnormalities in chronic uremic patients. Response to treatment with gemfibrozil. AB - Seventy-four patients with end stage renal failure were studied. Forty-six of them were on hemodialysis (HD) while 28 were on continuous ambulatory peritoneal dialysis (CAPD). In addition 56 nondialysis chronic renal failure (NDCRF) patients with various degree of renal failure were also studied. In all groups serum triglyceride concentrations were significantly higher and HDL cholesterol concentrations were significantly lower compared to age- and sex-matched controls. Total and LDL cholesterol were significantly higher in the NDCRF and CAPD patients compared to controls. In 55 patients (20 on HD, 13 on CAPD and 22 NDCRF) with severe hypertriglyceridemia or diminished HDL cholesterol gemfibrozil 300 mg b.i.d. per os was given for 6 months. Drug treatment reduced significantly serum triglycerides in all groups of patients and increased the levels of HDL cholesterol in CAPD patients. Moreover, a statistically significant decrease of the levels of total and LDL cholesterol was noticed in HD and NDCRF patients. During treatment no significant side effects were observed and liver and muscle enzymes remained within normal values. PMID- 8493457 TI - Parathyroid hormone and osteocalcin levels in plasma and ultrafiltrate during hemofiltration. AB - The effects of hemofiltration (HF) on serum levels of intact parathyroid hormone (PTH), as well as its mid-C regional and C-terminal fragments and bone Gla protein (bone gamma-carboxyglutamic acid, osteocalcin), were investigated in 17 patients during one session of HF. During HF there was a significant decrease in the serum concentrations of both intact PTH (p < 0.01), mid-C regional PTH (p < 0.01) and C-terminal PTH (p < 0.01) as well as in the osteocalcin concentrations (p < 0.01). There was a significant increase in serum calcium (p < 0.05) during the procedure and this increase correlated with the reduction in PTH (r = 0.56, p < 0.05). Mid-C regional PTH and osteocalcin were found in the ultrafiltrate of all patients, while intact PTH was found in the ultrafiltrate of 8 of 17 patients and C-terminal PTH was detected only in the ultrafiltrate of one patient. The data demonstrate that the permeability of HF membranes is high enough to cause filtration of both intact PTH, PTH fragments and osteocalcin. An inhibited secretion of PTH probably played a major part in reducing intact PTH in serum during HF. PMID- 8493458 TI - A model of reversible uremia employing isogenic kidney transplantation in the rat. Reversibility of secondary hyperparathyroidism. AB - Kidney transplanted patients with normalized kidney function may still exhibit a variety of problems such as bone problems, vascularly problems, and hormonal dysfunctions. A part of the symptoms may be persisting uremic symptoms, secondary to the pretransplanted period of chronic uremia. An experimental rat model, designed to the study of the reversibility of the chronic uremic implications is therefore described. A stable, severe chronic uremia was induced by 5/6 nephrectomy to inbred Lewis rats. Ten weeks later uremia was reverted by a successful isogenic rat kidney transplantation. During the period of chronic uremia the p-urea was elevated to an average of 21.8 +/- 0.9 mmol/l and p creatinine to 105.7 +/- 5.7 microM/l. The isogenic kidney transplantation resulted in reestablishment of normal kidney function with an average level of p urea of 7.6 +/- 0.2 mmol/l and p-creatinine 42.5 +/- 1.9 microM/l perfectly corresponding to the sham-operated rats, i.e. one-kidney rats. Reversibility of the secondary hyperparathyroidism due to chronic uremia was investigated in the model. In rats with chronic renal failure PTH increased from 52 +/- 4.9 pg/ml to 152 +/- 12.2 pg/ml and was normalized after transplantation. It is therefore concluded that the present described technique of introducing long term uremia followed up by a successful kidney transplantation in the rat may be a useful model to study the reversibility of different uremic manifestations. PMID- 8493459 TI - Two serious complications of circumcision. Case report. AB - Twins aged 19 years presented having been circumcised by an unqualified "itinerant circumciser" at the age of 2 1/2. In one the glans penis and corpus cavernosum were invisible, and the external urethral meatus was at the level of the mons pubis; the other had defects of the glans and corpus, iatrogenic hypospadias, and the end of the penis was protruding only 1.5 cm from the mons pubis. Both underwent successful reconstruction, and are normally sexually active. PMID- 8493460 TI - Traumatic rupture of the suspensory ligament of the penis. Case report. PMID- 8493461 TI - A pseudotumour of the bladder. Case report. AB - A case of pseudotumour involving the bladder is presented. The differential diagnostic importance of the lesion is stressed. PMID- 8493462 TI - Urodynamic manifestations associated with Ramsay-Hunt syndrome. Case report. PMID- 8493463 TI - Appendicovesical fistula. Case report. PMID- 8493464 TI - Intubated ureterotomy for ureteral obstruction following radiotherapy and radical hysterectomy. Case report. AB - A woman suffering from carcinoma of the cervix went through radical hysterectomy and radiotherapy. The treatment was complicated by obstruction of the lower left ureter which was dealt with by transureteroureterostomy. Eighteen months later she was admitted with severe stricture of the common pelvic ureter and massive retroperitoneal fibrosis. The afflicted ureteral segment was successfully reformed by intubated ureterotomy. PMID- 8493465 TI - Renal malignancy in von Hippel-Lindau's disease. Case reports. AB - We present our experience with 4 patients with von Hippel-Lindau's disease. They all had asymptomatic renal malignancy, and three patients had bilateral tumors. None of the patients had metastases from their renal tumors, but two patients had developed new tumors which demanded surgery. Abdominal computerized tomography was first choice in the initial evaluation, eventually supplemented by renal angiography. The treatment should be conservative, but bilateral nephrectomy and hemodialysis may be required. Screening of at-risk family members and close and lifelong follow-up is emphasized. PMID- 8493466 TI - Solitary metastasis in the gluteus maximus from renal cell carcinoma 12 years after nephrectomy. Case report. PMID- 8493467 TI - Urinary excretion patterns of pseudouridine and beta-aminoisobutyric acid in patients with tumours of the urinary bladder. AB - The preoperative and postoperative values of urinary pseudouridine:creatinine (phi:C) and beta-aminoisobutyric acid:creatinine (beta AIB:C) were estimated, in 192 patients with urothelial tumours of the bladder, 92 of whom had not previously been diagnosed. Urinary phi:C ratio correlated with the grade of tumour cell dysplasia (being highest in dysplasia grade 3), and to a lesser extent with the clinical stage. The treatment had no major influence on the excretion ratios. Decreased ratios, or those within the reference range, were associated with a better prognosis than increased ratios, and if both were increased at the same time the risk for progression of the disease was high. The biological tumour markers pseudouridine and beta-aminoisobutyric acid may be helpful in the diagnosis of tumours in the upper urinary tract, and in the follow up of patients with tumours of the bladder. PMID- 8493468 TI - Physical complications in patients treated with clean intermittent catheterization. AB - To characterize and quantify complications related to clean intermittent catheterization (CIC) 302 out-patients were followed for a mean period of 13 months. The main problems were minor bleeding in connection with the procedure and infections. Except for two patients with recurrent strictures, no serious urethral complications were detected. One or more episodes of cystopyelitis were experienced by 5.6% of the patients. Long term major problems of infectious origin affected only 2.6% while 24.5% had no signs of clinical infection during the follow-up period. UTI was more frequent in young patients, women, and men with supranuclear affection. Eight patients suffered from bladder stones and 1 patient from epididymitis. No serious radiological changes were detected in the upper urinary tract. No association was found between reported problems and changes in the patients' general condition, physical disability and length of previous CIC experience. PMID- 8493469 TI - Acidification of urine is not a feasible method for preventing encrustation of indwelling urinary catheters. AB - Encrusting deposits form on urinary catheters as a result of infection by bacteria which produce urease. Urease catalyses the hydrolysis of urea to produce ammonia, with the result that the pH of the urine increases and the deposits are precipitated. It has been suggested that acidification of urine may prevent this rise in pH and so prevent encrustation. Experiments were performed in vitro to determine whether acidification could be used to prevent the rise in pH when urease is present in urine. It was found that, in the presence of urease, the initial decrease in pH resulting from acidification was countered by further urea being converted into ammonia. Thus, although acidic washout solutions may dissolve encrusting deposits, acidification of urine is not a feasible method for preventing catheter encrustation. PMID- 8493470 TI - Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis. AB - A prospective study on the symptomatic effect of traditional Chinese acupuncture treatment and transcutaneous nerve stimulation (TENS) of the tibial nerve in patients with interstitial cystitis is presented. There was no difference in voiding frequency, mean voided volume, maximal voided volume or visual analogue scale symptom scores before or after treatment with either TENS or acupuncture. Only one patient became improved both subjectively and objectively after acupuncture for a short period of time. Even though the present material involves a small group of patients, it seems that the two methods, as applied in this study, have a very limited effect in patients with interstitial cystitis. PMID- 8493471 TI - Characterization of localized prostatic cancer: distribution, grading and pT staging in radical prostatectomy specimens. AB - Ninety-one patients underwent radical retropubic prostatectomy. Forty-three specimens were examined after limited sectioning (series 1) and 48 underwent whole organ serial step-sectioning at 5 mm intervals (series 2) of the removed prostate gland. The latter allowed a more extensive assessment of tumour localization, multicentricity, extension, pT-stage and grade. Eighty-eight percent of specimens in series 1 had free surgical margins compared with only 41% in series 2 (p = 0.00001). Preoperative tumour grading by fine-needle aspiration biopsy, TUR-chips or 1.2 mm core biopsies was in agreement with postoperative grading in the prostatectomy specimens in 48% of the cases in series 1 and 67% in series 2, respectively. In series 2, preoperative localization of the tumours by palpation was accurately assessed in 75% of cases when compared to the findings at step-sectioning. Sixty-eight percent of 40 eligible glands in series 2 contained multiple tumours. 12/13 cases of unifocal tumours (92%) were classified as large single tumours. The sections were divided into four peripheral and four central parts/octants, and the tumour localization was marked within these octants. The apical and middle third of the prostate contained tumour in all cases, whereas the basal (cranial part) was engaged in 35%. Small tumours were localized mainly in the periphery of the gland, with no significant difference between dorsal and ventral octants. However, large tumours were situated mainly in the dorsal peripheral octants, concomitant with an increased involvement of the ventral and central octants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493472 TI - Crystal adherence to rat bladder epithelium after long-term E. coli infection. AB - The normal urothelium is covered by a mucous coat which acts as an unspecific barrier against the adhesion of bacteria, cancer cells and crystals. Acute bacterial infections cause disruptions of the mucous coat and impairment of its anti-adherent property. The effect of long-term infection is, however, not known. Live E. coli were inoculated into rat urinary bladders and a persisting infection was obtained by creating a small bladder diverticulum. After 2, 10 and 21 days a crystal adhesion assay showed a twofold increased adherence to the urinary bladder in the infected rats compared to control (p < 0.001). One possible explanation could be an injury to the mucous coat. PMID- 8493473 TI - Painful caliceal calculi. The treatment of small nonobstructing caliceal calculi in patients with symptoms. AB - From 1984 to 1989 35 patients presented with uncharacteristic flank pain or recurrent urinary tract infections and small nonobstructing caliceal calculi. Thirty patients were treated; 13 with percutaneous stone extraction, 8 with extracorporeal shock wave lithotripsy, 3 with ureteroscopic stone manipulation and 2 by open surgery. Stone removal was successful in 39 patients and they were all relieved of their symptoms (86%). Stone size was decreased in 2 patients who felt a marked alleviation. Where the stone remained unaffected the symptoms persisted unabated. These observations suggest that small caliceal stones can cause pain. The results of treatment are such that it is justifiable to treat a small caliceal stone in patient suffering from flank pain of no other known cause. PMID- 8493474 TI - Desmopressin in elderly subjects with increased nocturnal diuresis. A two-month treatment study. AB - This study describes changes in diuresis during a two-month treatment with 40 micrograms desmopressin (Minirin) in a group of elderly persons with increased nocturnal diuresis and decreased ADH secretion. The average age of the men (n = 7) was 72 +/- 4 years and of the women (n = 14) 73 +/- 6 years. Nocturnal diuresis decreased after one and two months by 21% and 20% in the men and by 36% and 34% in the women, respectively. Half of the change persisted among the women but not among the men one month after the treatment. The decrease in nocturnal diuresis was greatest among those who, before the treatment, had a large part of their diuresis during the night. Diuresis during the day changed only insignificantly. Body weight did not change during treatment, nor did blood pressure, osmolality, sodium or potassium in serum. Sleep improved during treatment. In one case, side-effects were observed, with a feeling of swelling in the body and decreased diuresis in the morning. PMID- 8493475 TI - Kidney transplantation with and without prior dialysis therapy in diabetic patients with end-stage renal failure. AB - Cardiovascular disease is the main cause of death in diabetic patients. Uraemia seems to increase progression of cardiovascular morbidity. Therefore early transplantation even without pretransplant dialysis could be a way of slowing progression of cardiovascular complications in patients with endstage renal failure due to diabetic nephropathy. The risk for impaired graft survival and operation-induced complications have been considered contraindications for kidney transplantation without previous dialysis. To examine whether dialysis before transplantation influences the outcome of diabetic patients after kidney transplantation data from 125 diabetic patients receiving a kidney graft during 1973-1982 was retrospectively analyzed. Twenty-four of them were transplanted without previous dialysis. One-year patient survival was somewhat higher in patients transplanted without previous dialysis than in dialyzed patients (82 and 65%) but similar 7 years after transplantation (45% and 41%). Graft survival was also similar in both groups. Although the nondialyzed patients had had more myocardial infarctions before transplantation, prevalence of mortality in cardiovascular complications after transplantation were not increased compared with dialyzed patients. Previous dialysis did not influence surgery-related complications. PMID- 8493476 TI - Quality of life after kidney transplantation. A 10-22 years follow-up. AB - Out of 69 patients who were kidney transplanted from 1963 to 1978, 33 patients were alive with a functioning graft in 1988. Of these, 94% completed a questionnaire for the assessment of the quality of life. The total life situation was considered very good by 16%, good by 48%, medium by 29% and difficult by 6%. Nine patients (eight males) had a total of 16 children after the transplantation. There were 72% who were working full-time and the family income was acceptable for most of the patients. No patients had major psychological problems. Our conclusion is that this group of transplanted patients almost all reported a good quality of life and were almost fully rehabilitated in the second and third decade after their transplantation. PMID- 8493477 TI - Plasma vasopressin, catecholamines and atrial natriuretic factor during hemodialysis and sequential ultrafiltration. AB - In 13 patients with chronic renal failure on maintenance hemodialysis, plasma vasopressin, atrial natriuretic factor, catecholamines and renin activity were measured during ordinary hemodialysis with fluid removal, and during isolated isoosmotic ultrafiltration and a subsequent isovolemic hemodialysis. Concomitant with a significant fall in serum osmolality, plasma vasopressin decreased significantly from 6.3 +/- 0.8 to 3.8 +/- 0.4 pg/ml (p < 0.05). Predialytic plasma vasopressin was significantly correlated to serum osmolality (r = 0.62, p = 0.001). No such relationship was observed after dialysis. During isolated ultrafiltration (1.25 +/- 0.13 L) through 1 hour, no change in either osmolality or vasopressin was observed, whereas atrial natriuretic factor decreased (700 +/- 136 to 564 +/- 115 pg/ml, p < 0.05). Atrial natriuretic factor was excessively high at all times, and may explain the low plasma renin activity observed in these patients even after fluid removal. No consistent changes were observed in the catecholamines during hemodialysis or ultrafiltration alone, despite marked changes in blood pressure and heart rate. Thus, even in patients with chronic renal failure osmotic regulation of vasopressin seems intact, and volume reduction through ultrafiltration causes a decrease in atrial natriuretic factor. PMID- 8493478 TI - Effects of free perichondrial graft replacement of epiphyseal cartilage on bone growth. AB - An experimental study in 24 lambs was carried out to find an alternative tissue for the distal epiphyseal cartilage of the femur. The animals were divided into three groups. In the first group (n = 12) the left femoral distal epiphyseal cartilage was completely removed and replaced by a free perichondrial graft taken from the distal half of the scapula. In the second group (n = 6) the epiphyseal cartilage was removed and was not replaced by any tissue. The third group (n = 6) was used as control. After six months the legs in the first and third groups were of the same normal length while the legs in the second group were significantly shorter. We conclude that free perichondrial graft seems to be able to replace the epiphyseal cartilage and prevent retardation of growth. PMID- 8493479 TI - A comparison of the capsules around smooth and textured silicone prostheses used for breast reconstruction. A light and electron microscopic study. AB - A total of 18 women who had undergone modified radical mastectomy and tissue expansion for breast reconstruction were studied. When the expanders were replaced, nine patients had received smooth, gel-filled permanent prostheses and nine had received textured, gel-filled permanent prostheses. For medical reasons, e.g. capsular contraction, incorrectly placed or sized implant, an additional operation was performed, and then biopsy specimens from the capsules around the prostheses were taken and subsequently examined with the aid of the light and transmission electron microscope (TEM). A histologist was able to classify blindly 11 capsules out of 13 which were investigated by light microscopy in the correct groups and several differences between the capsules were found. Capsules around the smooth implants had a clear line of separation between the inner surface and the prosthesis, and formed a single collageneous layer. They were sparse in fibroblasts, which were long and thin. Capsules around textured implants consisted of two layers, the outer layer being compact with long, slender fibroblasts, and the inner one looking rugged with wavy bundles of collagen often splitting from each other, and with shorter and more rounded fibroblasts. The overall thickness seemed greater compared to the capsules around the smooth prostheses, which, on the other hand, showed a greater variation in thickness. To analyze collagen fibril diameters, sample sections were photographed at magnification 22,000 x in the TEM. The fibril diameters were measured with an interactive image analysis system (IBAS). The mean diameter of the collagen fibrils was 47.2 nm in the capsules around the smooth prostheses and 51.7 nm in the capsules around the textured prostheses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493480 TI - Differences between arterial and venous occlusion in microvascular surgery. AB - Between November 1985 and November 1988 11 patients developed arterial occlusion after microvascular anastomoses, 10 patients venous occlusions and five combined arterial and venous occlusions. We undertook a retrospective study to see whether colour, capillary refill, thermometry, or laser Doppler measurements could distinguish arterial and venous occlusions. Neither skin thermometry nor total backscattered light intensity change and flow band width (laser Doppler measurements) were significantly different (p > 0.05) between arterial and venous occlusions, but there were significant differences in colour (p = 0.006), capillary refill (p = 0.007), and laser Doppler flow (p = 0.02). The values obtained from cases with combined arterial and venous occlusions were like those of a venous occlusion or of an arterial occlusion or somewhere in between. Although none of the variables was diagnostic, we advise that the suspect vascular anastomosis should first be checked during reoperation. If an occluded anastomosis is found, one should also check the other anastomosis because occlusion of both artery and vein cannot be reliably detected. PMID- 8493481 TI - Endoscopic electrocautery of the thoracic sympathetic chain. A minimally invasive way to treat palmar hyperhidrosis. AB - Four hundred and fifty patients with palmar hyperhidrosis have undergone endoscopic thoracic sympathetic electrocautery since 1987 in our department. The procedure requires only minor modifications of standard laparoscopic and urological equipment. The median operating time for a bilateral procedure was 31 minutes (15-120), hospital stay was 1 day postoperatively (1-8), and patients returned to work within 4 (1-40) days. Complications in the whole material were few and mild, pneumothorax (n = 2), haemothorax (n = 1), and Horner's syndrome (n = 1). Five patients required reoperation (four because of primary failure to destroy the nerve and one for recurrent symptoms). The first consecutive 130 of these patients have been followed up by a questionnaire. At follow-up (median 196 days after operation, range 35-1419) all patients but three, who are awaiting reoperation were satisfied with the result. The discomfort and side effects of the operation were in most cases mild and short. This technique makes it possible to widen the indications for operation for people with palmar hyperhidrosis. PMID- 8493482 TI - Clinical experience with the Unilink/3M Precise microvascular anastomotic device. AB - The Unilink/3M Precise anastomotic device for microvascular anastomoses has been evaluated in 38 critical anastomoses in 26 selected patients. The microvascular anastomosis was usually completed within three minutes by a single surgeon. There was only one failure, when an arterial anastomosis clotted because of a technical error. In all patients tissue survival was dependent on patent mechanical anastomoses (critical anastomoses) and the follow-up period was more than three years. PMID- 8493483 TI - Lip and nose morphology in patients with unilateral cleft lip and palate from four Scandinavian centres. AB - Sixty patients with unilateral cleft lip and palate were compared for lip and nose appearance. All patients were photographed from an anteroposterior and a basal view at 7-10 years of age. The photographic registration method was tested for validity and accuracy. Although the four groups of 15 patients each were treated according to different protocols, many similarities were found with shorter lip heights at the cleft side and inclination of the rima oris. Asymmetry of nose and retropositioning at the cleft side naris were generally seen. Significantly straighter noses were demonstrated in the group treated with a two stage lip nose operation combined with nose plugs, and the two groups where vomer flaps were used showed the greatest deviation of the nose. PMID- 8493484 TI - One-stage closure of isolated cleft palate with the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification. I. Comparison of operative results. AB - The long term operative results of one-stage closure of isolated cleft palate with either the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification were evaluated and compared retrospectively. A total of 116 consecutive patients with isolated cleft palate who had been operated on at the age of 18-24 months were followed up until 17-20 years of age. Twenty-four of the patients needed one or more additional operations on the palate, mainly pharyngeal flaps (20%) and repair of fistulas (10%). There was no significant difference in the number of patients who needed further operations, either between the two different operations or between the sexes, but the patients who presented with the most extensive clefts required the most operations. PMID- 8493485 TI - A simple variant of surgical correction of prominent ears. Description of the surgical technique and follow-up examination in 36 patients. AB - A technically simple technique of otoplasty has been developed. An ovular skin excision is made on the posterior side of the auricle and then a transcartilaginous incision that corresponds to the future dorsal part of the antihelical fold. A parallel anterior incision of the anterior aspect of the cartilage helps to create a normal and harmonious configuration by smoothing the inward bending. Thirty-six patients were operated on and followed up for between six months and two years. The surgical results are satisfactory and there have been only two recurrences. PMID- 8493486 TI - Ultrastructural causes of rupture of hand tendons in patients with rheumatoid arthritis. A transmission and scanning electron microscopic study. AB - To identify the cause of rupture of hand tendons in patients with rheumatoid arthritis, we studied the underlying ultrastructural changes of the collagenous fibril systems. Samples of the flexor digitorum superficialis (n = 12) and the extensor digitorum communis (n = 20) were taken during tenosynovectomy. Tendons dissected at necropsy (n = 30) served as controls. Specimens were analysed by transmission and scanning electron microscopy. Interfibrillar dysplastic fibrils, "Luse bodies", and intracellular collagen were found in rheumatoid tissues. The diameters of collagen fibrils were significantly reduced compared with the control group (p < 0.01). The duration of the disease usually correlated well with the ultrastructural collagenous lesions. To provide optimum conditions for restoration of rheumatoid hand tendons, early synovectomy in rheumatoid patients seems warranted from the ultrastructural point of view. The alterations in collagen may explain the inadequate function of the hand tendons in patients with rheumatoid arthritis. PMID- 8493487 TI - Older type IV colles fractures treated with intramedullary insertion of a Rush pin. AB - Forty-four patients with 46 Older type IV Colles fractures, who had been treated with intramedullary insertion of a Rush pin were examined after a mean period of 16 months. At follow-up 28 (64%) of the patients had little or no pain, and four (9%) had pain almost all the time. Compared with the opposite side the median grip strength was 76%, flexion/extension was 81%, supination/pronation was 88%, and ulnar/radial movement was 73%. Three patients developed complications. The anatomical result was good or acceptable in 41 patients (93%) and poor in three (7%). According to Lucas and Sachtjen's modification of the Samiento scoring system the final results were excellent or good in 38 (86%) of the patients and fair in 5 (11%); in only one case was the result poor. The results are comparable with other methods of operative fixation. The procedure is relatively simple, and the complication rate is low. PMID- 8493488 TI - Cleft lip and palate, scoliosis, skeletal and cardiac malformations and other dysmorphic features in a child. Case report. AB - A girl aged 3 1/2 years presented with cleft lip and palate, facial asymmetry, brachycephaly, persistent ductus arteriosus, vertebral defects, and progressive scoliosis. There was, however, no significant mental and growth retardation. PMID- 8493489 TI - Preprosthetic reconstruction of eyesockets with mucosal grafts, and prevention of long term contractures. Case report. AB - Eight patients had eyesockets reconstructed with mucosal grafts. To prevent contraction of the grafts in the cavities postoperatively, a dental stent was stabilised in the socket by a metal pin attached to the frame of a pair of sunglasses. A similar device was also used in one case to expand a contracted eyesocket. PMID- 8493490 TI - Circulation of blood and viability after blunt suction lipectomy in pig buttock flaps. AB - Bilateral buttock flaps were raised in 13 Yorkshire pigs, and the viability and superficial blood flow were assessed by injection of fluorescein and laser Doppler flowmetry. One flap was then chosen at random from each pig to be defatted by blunt suction lipectomy. The opposite flap served as the control. Five and 30 minutes after lipectomy, the experimental flaps showed a 31% and 37% decrease in laser Doppler values (p < 0.05 and p < 0.01, respectively), measured 6 cm proximal to the margin of the fluorescein dye. There was no reduction in the values in the controls. One week after liposuction, the median area of flap necrosis in treated flaps was 4,615 mm2 (range 735-6,748) and in controls 4,104 mm (1,576-5,879). This difference was not significant (p = 0.24). Blunt suction lipectomy of the skin flaps did not significantly decrease the viability. The decreased skin circulation shown by laser Doppler soon after lipectomy may be a minor or temporary phenomenon. PMID- 8493491 TI - Six-hour preservation of the isolated working rat heart improved with University of Wisconsin solution. AB - University of Wisconsin (UW) solution was compared with modified St. Thomas cardioplegic solution for 6-hour preservation of isolated working rat hearts. The hearts (9 in each group) were arrested with the respective solution and stored, still cannulated, for 6 hours at 4 degrees C. After retrograde reperfusion for 30 minutes, antegrade perfusion was begun at constant left atrial and aortic pressures. Following 25 minutes of antegrade perfusion the hemodynamic recovery of the UW-preserved hearts was superior to that of the other hearts (cardiac output 46.0 +/- 4.8% of the preischemic control values in the UW group and 10.0 +/- 6.0% in the St. Thomas group, p < 0.01). The adenosine triphosphate content was significantly higher in the UW-preserved hearts (18.8 +/- 0.9 vs. 14.7 +/- 1.6 mumol/g dry weight, p < 0.05). No significant intergroup difference was found in aspartate aminotransferase leak or tissue glycogen. The study demonstrated both better function and enhancement of high-energy phosphates with UW solution vs. modified St. Thomas solution in isolated rat hearts, although without difference in enzyme leakage or tissue glycogen, after 6-hour preservation. PMID- 8493492 TI - Serum proteins provide a matrix for cultured endothelial cells on expanded polytetrafluoroethylene vascular grafts. AB - Endothelialization of prosthetic vascular grafts has been shown to increase patency. We studied the adhesion of cultured endothelial cells of adult human saphenous vein to serum protein coating on expanded polytetrafluoroethylene vascular grafts. The adhesion was compared with that on native or collagen type I coated grafts. Scanning electron microscopy was used to analyze the precoating and the appearance of the added cultured cells. Presence of radioactively labeled saphenous vein endothelial cells was compared between precoated and uncoated grafts before and after exposure to pulsatile plasma flow. The adherence of saphenous vein endothelial cells was markedly increased on grafts coated with serum proteins or collagen. On both graft types the cells formed confluent areas, which were also present after the plasma flow. The technique was designed to promote endothelialization, using autologous serum as the main source for both growth stimulation during culture and adherence of endothelial cells to grafts. The method may be clinically useful for precoating and endothelialization of vascular grafts. PMID- 8493493 TI - Influence of glucose-insulin-potassium on left ventricular function during coronary artery bypass grafting. AB - To evaluate the hemodynamic effect of glucose-insulin-potassium administered during cardiopulmonary bypass grafting (CABG), i.v. infusion of glucose 0.5 g, insulin 1.35 IU and potassium 0.25 mmol/kg b.w/hour was begun after induction of anesthesia and continued until aortic cross-clamping in seven patients. Seven controls underwent CABG without such infusion. The left ventricular ejection fraction was measured after i.v. injection of Tc-99m-HSA before and at termination of cardiopulmonary bypass (CPB), in conjunction with invasive measurements to obtain left ventricular pressure-volume indices at end-systole and end-diastole. Three-step transfusion from the oxygenator was given before and after CPB in order to assess left ventricular contractility during volume-load, using the end-systolic pressure-volume index. Left ventricular contractility remained unchanged after CPB in the patients given glucose-insulin-potassium but decreased significantly in the controls. The left ventricular passive diastolic properties were unchanged after the ischemic period in both groups. The arterial glucose concentration rose markedly in the infused group (7.3-18.5 mmol/l) and moderately (6.4-8.2) in the controls. Glucose-insulin-potassium infusion thus favorably influenced left ventricular function during CABG by preventing decrease in contractility after CPB. PMID- 8493494 TI - The role of the internal thoracic artery in the sternal blood supply. AB - The altered arterial supply to the sternum after use of the internal thoracic artery in coronary bypass surgery was studied by delineation of the sternal arterial system with plastic material and by injection of ink/barium contrast for radiography and microscopy. The study was performed on 17 anterior chest walls from human cadavers. The total arterial supply was charted before and after 'harvest' of the internal thoracic artery. The dominant blood supply to the sternum was found to be periosteal and derived almost exclusively from branches of the internal thoracic artery. Following harvest of that artery, the arterial supply to the upper part of the corpus sterni was compromised, and based only on sparse ramifications to the periosteal membrane from the thoracoacromial artery via branches from the pectoralis major muscle. PMID- 8493495 TI - Total parenteral nutrition in patients with intra-aortic balloon counterpulsation. AB - The effects of total parenteral nutrition (TPN) were studied in nine of 19 patients with intra-aortic balloon pumping TPN (c. 27 kcal/kg/day) was begun 3 hours after the start of pumping. The non-protein caloric source was composed of hypertonic dextrose and fat emulsion (60% and 40%). The nitrogen intake was 1 g/150-200 kcal/day. The ten control patients received 5% dextrose in corresponding volume/hour. Hemodynamic studies were performed before and 24, 48 and 72 hours after the start of counterpulsation. The predicted and the observed resting energy expenditure were recorded in both patient groups during counter pulsation. Systemic and pulmonary vascular resistance differed significantly between the groups. Cardiac function improved in both groups. In the TPN group the measured resting energy expenditure increased by 33% more than predicted on day 2 and by 56% on day 3 and in the controls the figures were 31% and 40%--all rises significant. Total parenteral nutrition with low fat content thus alters the hemodynamic equilibrium without clinically significant effects in patients undergoing intra-aortic balloon pumping. These patients are hypermetabolic and should receive artificial nutrition as soon as possible. PMID- 8493496 TI - Hemodynamic status in repaired tetralogy of Fallot assessed by Doppler echocardiography and cardiac catheterization. Comparisons with healthy subjects and elucidation of factors associated with cardiorespiratory function. AB - Thirty-four patients were studied after corrective surgery for tetralogy of Fallot (mean follow-up 10 years) and compared with healthy matched controls. All underwent Doppler echocardiography, spirometry and treadmill exercise test. Post operative cardiac catheterization had been performed on 26 (76%) of the patients and showed poor hemodynamic results in four (15%). Significant correlations of pressure gradients obtained from catheterization and estimated by Doppler echocardiography were right ventricular to right atrial (r = 0.77), pulmonary outflow (r = 0.75), pure valvular pulmonary outflow (r = 0.94) and diastolic pulmonary pressure gradients (r = 0.53). Pulmonary outflow gradients and right ventricular to right atrial pressure gradients estimated from tricuspid regurgitation jets were significantly increased in the patients. Diastolic pulmonary artery pressure, vital capacity and ventilatory anaerobic threshold were independent factors of maximal oxygen consumption. It is suggested that Doppler-derived diastolic pulmonary artery pressure, lung function studies and exercise testing with assessment of the ventilatory anaerobic threshold should be included in follow-up after repair of Fallot's tetralogy. PMID- 8493497 TI - Treatment of primary spontaneous pneumothorax with intrapleural tetracycline instillation or thoracotomy. Follow-up of management program. AB - Spontaneous pneumothorax has a high incidence of recurrence if treated only with intercostal drainage. A series of 404 patients in a special treatment program is presented. Early thoracoscopy was performed in 97%. The 86 patients (21%) then found to have true cyst (> 2 cm) were subjected to thoracotomy with removal of cyst and mechanical pleurodesis, and in the others a dilute tetracycline solution was instilled intrapleurally, followed by intercostal tube drainage. There was no recurrence of pneumothorax in the group treated with thoracotomy, but 8% recurrence in the tetracycline-treated group. Repeated thoracoscopy was performed in 21 of the 25 patients with recurrent pneumothorax, and thoracotomy with resection of large cyst in four. The probable cause of recurrence was identified in 21 cases, making the true recurrence rate 1% (4 patients). The mean hospital stay was 7.6 days for the patients with thoracotomy and 4.3 days for the tetracycline-treated group. PMID- 8493498 TI - Aspergilloma within cavitating pulmonary carcinoma. Case report. AB - Aspergillosis was diagnosed in a 69-year-old man presenting with blood-stained sputum, and was treated with an antifungal agent. As radiographic lesions persisted after 3 months, left upper lobectomy was performed. The surgical specimen revealed pulmonary carcinoma associated with an intracavitary aspergillar infection. PMID- 8493499 TI - Intrathoracic splenosis. Report of a case simulating esophageal leiomyoma. AB - Intrathoracic splenosis is a rare sequel of left thoracoabdominal injury. A case simulating esophageal leiomyoma is presented. As in most earlier cases, the diagnosis was established only at thoracotomy. As splenosis is asymptomatic and may have some beneficial immunologic effects, surgical removal is inadvisable. The 23 previously published cases and the possibility of nonsurgical diagnosis are discussed. PMID- 8493500 TI - Surgical intervention following failed percutaneous coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed on 725 occasions at the National Hospital of Norway in 1981-1990. Acute surgical intervention was necessary within 24 hours after PTCA in 15 cases, on indications that included coronary artery dissection (8 cases) and acute thrombotic occlusion (5). Electrocardiographic signs of ischemia were present in 11 patients with anginal pain, while two had severe angina but normal electrocardiogram. Two patients had a non-ischemic indication for surgery. Despite surgery, ten of the 15 patients had acute myocardial infarction. One of the ten died. At follow-up nine of 12 patients were free from angina and three had recurrent symptoms. PMID- 8493501 TI - [The passage of antibiotics into human ginigival fluid. A review of the literature]. AB - Many antibiotics are utilized in dentistry, particularly in periodontology, to treat aggressive forms of periodontitis. In order to be efficient, both on a clinical and on a microbiological point of view, these substances must be present in sufficient concentrations in the gingival sulcus. The aim of the present literature review was to summarize studies concerning the passage of the various families of antibiotics into the gingival fluid, together with their spectrum and clinical efficacy. Whereas certain antibiotics, such as natural or semisynthetic tetracyclines or spiramycin, are able to accumulate in gingival fluid comparatively to serum, others, like metronidazole, tinidazole and rifampicin, have been found in similar concentrations in the fluid as in serum. Some other antibiotics, such as erythromycin and ampicillin, are, on the contrary, less concentrated in crevicular fluid as compared to blood. One has to remember that any systemic antibiotic treatment will be useful, clinically and microbiologically speaking, only when a mechanical therapy is also applied. PMID- 8493502 TI - [The salivary content of Streptococcus mutans in Basel children and adolescents]. AB - The search for a feasible method to estimate the caries risk in humans is going on since several years. Such risk assessments should especially be performed in persons clinically suspected to be at risk. The quantitative determination of Mutans Streptococci (SM) in whole saliva has been proposed to serve as a measure of the caries risk. SM tests have been performed in a group of 5743 5 to 16 year old children and adolescents living in the city of Basle in 1991. Levels of SM in whole saliva were correlated with caries prevalence both in the deciduous and permanent teeth. SM counts have become a valuable diagnostic tool for the early identification of children at risk for caries development. SM tests have equally become a helpful pedagogic instrument used to motivate patients for individual prophylactic activities. PMID- 8493503 TI - S-100 protein in normal and pathologic oral tissues. A review. AB - S-100 protein is an acidic calcium binding protein widely distributed in different tissues and cells of different origin. The precise biological role of S 100 is still unknown, but several features suggest a function activity for this protein. Oral tissues have not been extensively studied for S-100 protein presence. Here, we review the investigations of S-100 protein content in normal oral tissues and oral pathological lesions. The immunolocalization of this protein is used to demonstrate evidence of neuroectodermal histogenesis and is useful in the differential diagnosis of certain neoplasms or proliferative conditions. PMID- 8493504 TI - [Normal and induced Hg release from different amalgams]. AB - In an experimental investigation of 20 subjects who had no amalgam fillings, the mercury load from artificially applied, standardised amalgam surfaces was tested for one product containing gamma-2 and one free of gamma-2 respectively. The product which contained gamma-2 caused a statistically significant increase in Hg concentrations in the 24-hour urine sample. After challenge with Dimaval, an intensifying effect on the elimination rate could be detected, although all values clearly remained below a toxicologically relevant concentration. In order to avoid unnecessary exposure to heavy metals, the use of gamma-2-free amalgams and, in the long term, the development of optimised filling materials and intensification of prophylactic measures for prevention of dental caries are to be welcomed. PMID- 8493505 TI - [Sanitary measures in HIV periodontitis. The long-term results with 2 patients]. PMID- 8493506 TI - [The psychosomatic aspects of periodontopathies]. PMID- 8493507 TI - [The current situation of the dental product market in Switzerland. Interview by Kurt Venner]. PMID- 8493508 TI - ["The dental hygienist will never compete with a dentist". Interview by Kurt Venner]. PMID- 8493509 TI - Assessment of exposure rate and collective effective dose equivalent in the city of Baghdad due to natural gamma radiation. AB - Exposure rate measurements in the city of Baghdad were initiated in June 1981. The average exposure rate, the average annual effective dose equivalent and the collective effective dose equivalent are assessed. The data are presented according to the eleven municipal divisions of the city. The average exposure rate was 6.9 microR h-1 and an average annual effective dose equivalent of 4.5 x 10(-4) Sv year-1. The collective effective dose equivalent is 1.81 x 10(3) man Sv year-1. PMID- 8493510 TI - Organochlorine pesticide residues and PCBs in Danish otters (Lutra lutra). AB - Tissues (71 liver, 2 muscle) of 73 otters found dead in Denmark between 1980 and 1990 were analyzed for organochlorine pesticide residues and PCBs. Geometric means of contaminant concentrations were generally low, but some otters had PCB concentrations considered to be of concern; a greater proportion of these came from isolated populations away from the main population centre in Limfjord. Animals dying of unknown causes had greater concentrations of PCBs than those dying by drowning or in traffic accidents. Adults had significantly higher concentrations of PCBs. Contaminant concentrations were strongly intercorrelated. Concentrations of DDE and PCBs declined significantly during the study period. A sample of otter spraints (faeces) collected in 1990 had low mean concentrations of contaminants. It is concluded that current concentrations of organochlorine pesticide residues and PCBs are unlikely to pose a threat to otter populations. PMID- 8493511 TI - The human cornucopia. PMID- 8493512 TI - "MegaYAC" library. PMID- 8493513 TI - Interdisciplinary symposia. PMID- 8493514 TI - Judging science. PMID- 8493515 TI - Judging science. PMID- 8493516 TI - Measure for measure in science. PMID- 8493517 TI - National Institutes of Health. Glossy strategic plan hits the streets. PMID- 8493518 TI - Women at NIH. Task force: level the playing field. PMID- 8493519 TI - Old feuds, new finds mark anthropologists' meeting. PMID- 8493520 TI - Neuroscience. The remembrance of blinks past. PMID- 8493522 TI - Sixth AIDS case traced to Florida dentist. PMID- 8493521 TI - Forensic science. Botanical witness for the prosecution. PMID- 8493524 TI - Biotech sails into heavy financial seas. PMID- 8493523 TI - Biotech gets a grip on cell adhesion. PMID- 8493526 TI - Stand and deliver: getting peptide drugs into the body. PMID- 8493525 TI - Going back to the future with small synthetic compounds. PMID- 8493527 TI - New startups move in as gene therapy goes commercial. PMID- 8493528 TI - Molecular advances in cardiovascular biology. PMID- 8493529 TI - Tissue engineering. AB - The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts to provide solutions to tissue creation and repair. PMID- 8493530 TI - The basic science of gene therapy. AB - The development over the past decade of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies. However, despite substantial progress, a number of key technical issues need to be resolved before gene therapy can be safely and effectively applied in the clinic. Future technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful practice of gene therapy. PMID- 8493531 TI - New challenges in human in vitro fertilization. AB - This review assesses some scientific and ethical problems with human in vitro fertilization. Improved selection of viable embryos, better culture conditions, and greater understanding of the uterine environment will increase success and prevent multiple pregnancy. Further advances will also improve oocyte cryopreservation, in vitro maturation of oocytes, knowledge of sperm function, and sperm microinjection. Preimplantation diagnosis will help avoid genetic diseases and increase understanding of embryonic defects and the viability of zygotes. The greatest ethical problem with all these developments seems to be delivery of these complex treatments when health-care resources are increasingly limited. PMID- 8493532 TI - Identifying strategies for immune intervention. AB - In recent years the molecular basis of antigen recognition by T cells has been unraveled and the various pathways that control T cell activation and functional specialization have been defined. Consequently, it is now possible to delineate various strategies for intervention with the immune system to design protective vaccines, to induce an effective response to tumor antigens, and to control graft rejection and autoimmune diseases. PMID- 8493533 TI - Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. AB - Antigen receptor genes are assembled by site-specific DNA rearrangement. The recombination activator genes RAG-1 and RAG-2 are essential for this process, termed V(D)J rearrangement. The activity and stability of the RAG-2 protein have now been shown to be regulated by phosphorylation. In fibroblasts RAG-2 was phosphorylated predominantly at two serine residues, one of which affected RAG-2 activity in vivo. The threonine at residue 490 was phosphorylated by p34cdc2 kinase in vitro; phosphorylation at this site in vivo was associated with rapid degradation of RAG-2. Instability was transferred to chimeric proteins by a 90 residue portion of RAG-2. Mutation of the p34cdc2 phosphorylation site of the tumor suppressor protein p53 conferred a similar phenotype, suggesting that this association between phosphorylation and degradation is a general mechanism. PMID- 8493534 TI - Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry. AB - Human immunodeficiency virus type-1 (HIV-1) DNA and messenger RNA sequences in both cell lines and blood obtained directly from HIV-1-infected patients were amplified by polymerase chain reaction and hybridized to fluorescein-labeled probes in situ, and the individually labeled cells were analyzed by flow cytometry. After flow cytometric analysis, heterogeneous cell populations were reproducibly resolved into HIV-1-positive and -negative distributions. Fluorescence microscopy showed that the cellular morphology was preserved and intracellular localization of amplified product DNA was maintained. Retention of nonspecific probe was not observed. Analysis of proviral DNA and viral messenger RNA in cells in the blood of HIV-1-infected patients showed that the HIV-1 genome persists in a large reservoir of latently infected cells. With the use of this technique it is now possible to detect single-copy DNA or low-abundance messenger RNA rapidly and reproducibly in a minor subpopulation of cells in suspension at single-cell resolution and to sort those cells for further characterization. PMID- 8493535 TI - Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains. AB - The CD4 antigen is a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigens and is also a receptor for the human immunodeficiency virus. the extracellular portion of CD4 is predicted to fold into four immunoglobulin-like domains. The crystal structure of the third and fourth domains of rat CD4 was solved at 2.8 angstrom resolution and shows that both domains have immunoglobulin folds. Domain 3, however, lacks the disulfide between the beta sheets; this results in an expansion of the domain. There is a difference of 30 degrees in the orientation between domains 3 and 4 when compared with domains 1 and 2. The two CD4 fragment structures provide a basis from which models of the overall receptor can be proposed. These models suggest an extended structure comprising two rigid portions joined by a short and possibly flexible linker region. PMID- 8493536 TI - Localization of a memory trace in the mammalian brain. AB - The localization of sites of memory formation within the brain has proven to be a formidable task even for simple forms of learning and memory. In order to localize a particular site of memory formation within the brain, the rabbit eyeblink response was classically conditioned while regions of the cerebellum or red nucleus were temporarily inactivated by microinfusions of the gamma aminobutyric acid agonist muscimol. Cerebellar inactivation completely blocked learning but had no effect on subsequent learning after inactivation, whereas red nucleus inactivation did not prevent learning but did block the expression of conditioned responses. The site of memory formation for this learned response thus appears to be localized within the cerebellum. PMID- 8493537 TI - Induction of G alpha i2-specific antisense RNA in vivo inhibits neonatal growth. AB - Guanosine triphosphate-binding regulatory proteins (G proteins) are key elements in transmembrane signaling and have been implicated as regulators of more complex biological processes such as differentiation and development. The G protein G alpha i2 is capable of mediating the inhibitory control of adenylylcyclase and regulates stem cell differentiation to primitive endoderm. Here an antisense RNA to G alpha i2 was expressed in a hybrid RNA construct whose expression was both tissue-specific and induced at birth. Transgenic mice in which the antisense construct was expressed displayed a lack of normal development in targeted organs that correlated with the absence of G alpha i2. The loss of G alpha i2 expression in adipose tissue of the transgenic mice was correlated with a rise in basal levels of adenosine 3',5'-monophosphate (cAMP) and the loss of receptor-mediated inhibition of adenylylcyclase. These data expand our understanding of G protein function in vivo and demonstrate the necessity for G alpha i2 in the development of liver and fat. PMID- 8493538 TI - Cue-invariant shape selectivity of macaque inferior temporal neurons. AB - The perception of shape is independent of the size and position of the shape and also of the visual cue that defines it. The same shape can be recognized whether defined by a difference in luminance, by motion, or by texture. Experiments showed that the shape selectivity of individual cells in the macaque inferior temporal cortex did not vary with the size and position of a shape and also did not vary with the visual cue used to define the shape. This cue invariance was true for static luminance and texture cues as well as for relative motion cues- that is, for cues that are processed in ventral and dorsal visual pathways. The properties of these inferior temporal cells meet the demands of cue-invariant shape coding. PMID- 8493539 TI - Induction of olfactory receptor sensitivity in mice. AB - Repeated exposure to olfactory ligands (odorants) increased peripheral olfactory sensitivity in mice. For two unrelated ligands, androstenone and isovaleric acid, induction of olfactory sensitivity was odorant-specific and occurred only in inbred strains that initially had low sensitivity to the exposure odorant. These data demonstrate stimulus-induced plasticity in a sensory receptor cell, suggesting a form of stimulus-controlled gene expression. Induction with two unrelated odorants implies that olfactory induction is a general phenomenon that may occur in a large fraction of the human population. PMID- 8493540 TI - NRC report on DNA typing. PMID- 8493541 TI - NRC report on DNA typing. PMID- 8493542 TI - The rocky road to a data highway. PMID- 8493543 TI - Virtual libraries, complete with journals, get real. PMID- 8493544 TI - Healy slams Clinton's NIH budget. PMID- 8493545 TI - Breast cancer funding. An expert panel advises, and the Army consents. PMID- 8493546 TI - Dental Institute report has NIH down in the mouth. PMID- 8493547 TI - Promising protein for Parkinson's. PMID- 8493549 TI - A faster walk along the genome. PMID- 8493548 TI - Imanishi-Kari says her new data shows she was right. PMID- 8493550 TI - Research in Japan. Computer firms look to the brain. PMID- 8493551 TI - A new twist on integrins and the cytoskeleton. PMID- 8493552 TI - On the crawling of animal cells. AB - Cells crawl in response to external stimuli by extending and remodeling peripheral elastic lamellae in the direction of locomotion. The remodeling requires vectorial assembly of actin subunits into linear polymers at the lamella's leading edge and the crosslinking of the filaments by bifunctional gelation proteins. The disassembly of the crosslinked filaments into short fragments or monomeric subunits away from the leading edge supplies components for the actin assembly reactions that drive protrusion. Cellular proteins that respond to lipid and ionic signals elicited by sensory cues escort actin through this cycle in which filaments are assembled, crosslinked, and disassembled. One class of myosin molecules may contribute to crawling by guiding sensory receptors to the cell surface, and another class may contribute by imposing contractile forces on actin networks in the lamellae. PMID- 8493553 TI - Kinetics of folding of the all-beta sheet protein interleukin-1 beta. AB - The folding of the all-beta sheet protein, interleukin-1 beta, was studied with nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and fluorescence. Ninety percent of the beta structure present in the native protein, as monitored by far-ultraviolet circular dichroism, was attained within 25 milliseconds, correlating with the first kinetic phase determined by tryptophan and 1-anilinonaphthalene-8-sulfonate fluorescence. In contrast, formation of stable native secondary structure, as measured by quenched-flow deuterium hydrogen exchange experiments, began after only 1 second. Results from the NMR experiments indicated the formation of at least two intermediates with half-lives of 0.7 to 1.5 and 15 to 25 seconds. The final stabilization of the secondary structure, however, occurs on a time scale much greater than 25 seconds. These results differ from previous results on mixed alpha helix-beta sheet proteins in which both the alpha helices and beta sheets were stabilized very rapidly (less than 10 to 20 milliseconds). PMID- 8493554 TI - Substrate phage: selection of protease substrates by monovalent phage display. AB - A method is described here for identifying good protease substrates among approximately 10(7) possible sequences. A library of fusion proteins was constructed containing an amino-terminal domain used to bind to an affinity support, followed by a randomized protease substrate sequence and the carboxyl terminal domain of M13 gene III. Each fusion protein was displayed as a single copy on filamentous phagemid particles (substrate phage). Phage were then bound to an affinity support and treated with the protease of interest. Phage with good protease substrates were released, whereas phage with substrates that resisted proteolysis remained bound. After several rounds of binding, proteolysis, and phagemid propagation, sensitive and resistant substrate sequences were identified for two different proteases, a variant of subtilisin and factor Xa. The technique may also be useful for studying the sequence specificity of a variety of posttranslational modifications. PMID- 8493555 TI - Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. AB - The cytotoxicity of human natural killer (NK) cells is modulated by the major histocompatibility complex human leukocyte antigen (HLA)-C molecules on the surface of the target cell. Alloreactive NK cells specific for the NK-1 alloantigen could be reproducibly generated from individuals that were homozygous for HLA-C with asparagine at residue 77 and lysine at residue 80 [HLA C(Asn77,Lys80)] by stimulation with target cells that were homozygous for HLA C(Ser77,Asn80); the reciprocal stimulation yielded NK cells specific for the NK-2 alloantigen. However, neither homozygous target cell stimulated the generation of alloreactive NK cells from heterozygous individuals. Thus, these data reveal an unanticipated difference between human NK alloreactivity defined by this system and murine "hybrid resistance." PMID- 8493556 TI - Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. AB - Pseudomonas aeruginosa is an opportunistic human pathogen that causes a variety of infections in immunocompromised hosts and individuals with cystic fibrosis. Expression of elastase, one of the virulence factors produced by this organism, requires the transcriptional activator LasR. Experiments with gene fusions show that gene lasl is essential for high expression of elastase. The lasl gene is involved in the synthesis of a diffusible molecule termed Pseudomonas autoinducer (PAI). PAI provides P. aeruginosa with a means of cell-to-cell communication that is required for the expression of virulence genes and may provide a target for therapeutic approaches. PMID- 8493557 TI - GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. AB - A potent neurotrophic factor that enhances survival of midbrain dopaminergic neurons was purified and cloned. Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake. These effects were relatively specific; GDNF did not increase total neuron or astrocyte numbers nor did it increase transmitter uptake by gamma aminobutyric-containing and serotonergic neurons. GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons. PMID- 8493558 TI - AIDS 1993: unanswered questions. PMID- 8493559 TI - DNA fingerprinting: the NRC report. PMID- 8493561 TI - Liver stem cells. PMID- 8493560 TI - Directed mutation. PMID- 8493562 TI - Another reversal for the AIDS Vaccine Trial? PMID- 8493563 TI - New tumor suppressor gene captured. PMID- 8493564 TI - AIDS research: the mood is uncertain. PMID- 8493565 TI - What are the correlates of protection? PMID- 8493566 TI - How can viral variation be overcome? PMID- 8493567 TI - What HIV parts should be the basis of a vaccine? How should they be presented to the immune system? PMID- 8493568 TI - AIDS conference in Berlin offers plenty of hidden gems. PMID- 8493569 TI - AIDS the unanswered questions: four European researchers. PMID- 8493570 TI - Slowing the spread of HIV: agenda for the 1990s. PMID- 8493571 TI - How does HIV cause AIDS? AB - Many questions have been posed about acquired immunodeficiency syndrome (AIDS) pathogenesis. Is human immunodeficiency virus (HIV) both necessary and sufficient to cause AIDS? Is AIDS essentially an autoimmune disease, triggering apoptosis, or is virus infection the cause of T helper lymphocyte depletion? What is the significance of HIV tropism and the role of macrophages and dendritic cells in AIDS? Is there viral latency and why is there usually a long period between infection and AIDS? Is HIV variation a crucial aspect of its pathogenesis and, if so, do virulent strains emerge? Although this article provides few definitive answers, it aims to focus commentary on salient points. Overall, it is increasingly evident that both the tropism and burden of HIV infection correlate closely with the manifestations of disease. PMID- 8493572 TI - Scientific and social issues of human immunodeficiency virus vaccine development. AB - Development of a preventive immunogen for human immunodeficiency virus (HIV) infection is a national priority. The complexities associated with HIV host-virus interactions, coupled with the rapid progression of the HIV epidemic worldwide, have necessitated lowering expectations for an HIV vaccine that is 100 percent effective and have raised important scientific and nonscientific issues regarding development and use of preventive and therapeutic HIV vaccines. PMID- 8493573 TI - A strategy for the solid-phase synthesis of oligosaccharides. AB - Repeating glycosidic linkages of oligosaccharides can be synthesized by solid phase methods. Glycals were attached to a polystyrene copolymer with a silyl ether bond and were activated to function as glycosyl donors with 3,3 dimethyldioxirane. Glycosidation was performed by reactions with a solution-based acceptor (itself a glycal). Excess acceptor and promoter were removed by rinsing after each coupling, and the desired oligosaccharides were then easily obtained from the polymer by the addition of tetra-n-butylammonium fluoride. By this method, glycosidations are stereospecific and interior deletions are avoided. PMID- 8493574 TI - Identification of the von Hippel-Lindau disease tumor suppressor gene. AB - A gene discovered by positional cloning has been identified as the von Hippel Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei. PMID- 8493575 TI - Repression of MHC class I gene promoter activity by two-exon Tat of HIV. AB - Major histocompatibility complex (MHC) class I molecules are the major receptors for viral peptides and serve as targets for specific cytotoxic T lymphocytes. Human immunodeficiency virus-type 1 (HIV-1) specifically decreased activity of an MHC class I gene promoter up to 12-fold. Repression was effected by the HIV-1 Tat protein derived from a spliced viral transcript (two-exon Tat). These studies define an activity for two-exon Tat distinct from that of one-exon Tat and suggest a mechanism whereby HIV-1-infected cells might be able to avoid immune surveillance, allowing the virus to persist in the infected host. PMID- 8493576 TI - Protection against vaginal SIV transmission with microencapsulated vaccine. AB - Although protection in animal models against intravenous challenges with simian immunodeficiency virus (SIV) has been reported, no previous vaccines have protected against a heterosexual route of infection. In this study, five of six macaques were protected against vaginal challenge when immunized with formalin treated SIV in biodegradable microspheres by the intramuscular plus oral or plus intratracheal route. Oral immunization alone did not protect. After a second vaginal challenge, three of four intramuscularly primed and mucosally boosted macaques remained protected. The data suggest that protection against human immunodeficiency virus vaginal transmission could be provided by microsphere based booster vaccines when used to immunize women who are systemically primed. PMID- 8493577 TI - High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia. AB - Ataxia-telangiectasia (A-T) is an inherited human disease associated with neurologic degeneration, immune dysfunction, and high cancer risk. It has been proposed that the underlying abnormality in A-T is a defect in genetic recombination that interferes with immune gene rearrangements and the repair of DNA damage. Recombination was studied in A-T and control human fibroblast lines by means of two recombination vectors. Unexpectedly, spontaneous intrachromosomal recombination rates were 30 to 200 times higher in A-T fibroblast lines than in normal cells, whereas extrachromosomal recombination frequencies were near normal. Increased recombination is thus a component of genetic instability in A-T and may contribute to the cancer risk seen in A-T patients. PMID- 8493578 TI - Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein. AB - The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1 dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage specific effector functions such as lymphokine production with cell cycle progression in activated T cells. PMID- 8493579 TI - Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. AB - A human complementary DNA was isolated that encodes a widely expressed protein, hSos1, that is closely related to Sos, the product of the Drosophila son of sevenless gene. The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras from yeast. A fragment of hSos1 encoding the CDC25-related domain complemented loss of CDC25 function in yeast. This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. Mammalian cells overexpressing full length hSos1 had increased guanine nucleotide exchange activity. Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 (GRB2) in vivo and in vitro. This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1. PMID- 8493580 TI - [Clinical study of rheumatoid interstitial lung disease evaluated by high resolution CT]. AB - High resolution computed tomographic (HRCT) scans were obtained in 215 patients with rheumatoid arthritis to assess pulmonary fibrosis (PF). We classified the HRCT appearances as five-point scale (0-4) based on the degrees of PF. The results were as follows: 1. We found 117 cases (54.4%) of PF on HRCT. 2. Patients with PF (grade 1-4) showed significantly increased leucocyte cell counts and significantly worsened pulmonary function test than patients without PF (grade 0). 3. Patients with advanced articular involvement had significantly higher prevalence of PF than others without them. 4. Patients who were previously or currently receiving gold sodium thiomalate (GST) injection or administration of methotrexate had higher prevalence of PF than others. However, patients who were receiving long term GST therapy (1 year long or sigma 1000 mg) had slightly lower prevalence of PF than others. This finding suggests that dose-dependent lung injury is not related to GST therapy. 5. Patients with advanced PF (grade 3, 4) had high prevalence of male sex, smoker, extraarticular manifestation. PMID- 8493581 TI - [Clinical significance of electroencephalograph in patients with systemic lupus erythematosus]. AB - The electroencephalograms (EEGs) of 120 patients with systemic lupus erythematosus (SLE), were evaluated with regard to clinical manifestations and laboratory findings. On the initial 120 records, abnormal EEGs were observed in 109 patients (90.8%). Epileptiform patterns were also observed in 33 patients (27.5%). Diffuse alpha wave, theta wave, and delta wave appeared to be unique findings of basic wave activity in EEGs of SLE patients. Paroxysmal abnormalities of spike and wave complex, spike, and sharp wave were frequently observed. These paroxysmal abnormalities appeared to be easily exaggerated by hyperventilation or sleep. Focal abnormal discharges were also observed. The incidence of abnormal EEGs of the patients with central nervous system involvement (CNS lupus), did not differ from that of non-CNS lupus i.e. 24/30 (80.0%) vs 82/93 (88.2%). On the other hand, regarding the severity of abnormal EEGs, CNS lupus manifested severer findings than those of non-CNS lupus. As to the EEG abnormality, female patients, younger patients less than 30 years old, flared patients, and patients receiving prednisolone more than 30 mg/day had severer EEG findings than those of each counterparts. The patients who had once manifested neuropsychiatric disorders and/or immunologic abnormalities (anti-deoxynucleic acid antibody, anti-DNA antibody), showed severe findings on EEG. Epileptiform patterns were frequently observed in patients receiving lower prednisolone doses (30 mg/day or less), although they did not correlate with disease activity. Patients with arteriosclerosis obliterans or aortitis syndrome, demonstrated only mild abnormalities on EEGs and they had not shown any epileptiform patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493582 TI - [Long-term retrospective study of patients with connective tissue diseases accompanied by pulmonary hypertension]. AB - To determine clinical and serological features that are related with the prognosis of connective tissue diseases with pulmonary hypertension (PH), we studied a long-term prognosis of 14 patients (4 SLE, 1 PSS, 3 MCTD, 2 primary Sjogren's syndrome, and 5 OL) accompanied by PH. The patients were divided into three groups; group A (4 cases) that is alive for 5-12 years until present, group B (6 cases) in which PH was the main cause of death, and group C (4 cases) was dead of pulmonary fibrosis and pericardial tamponade. No significant difference was observed in background connective tissue diseases among the three groups. However, the mean ages at the onset of PH was obviously younger in group B (25.7 yrs.) than both in group A (38.3 yrs.) and in group C (42.0 yrs.) (group A vs group B, p < 0.02, and group B vs group C, p < 0.05). Sudden death occurred in 5 of the 6 in group B, whereas it was not observed either in group A or in group C. Also, the interval between onset of PH and death was shorter in group B (1.3 yrs.) than in group C (3.5 yrs.). The incidence of digital necrosis and pericardial effusion was higher in group B (83% and 83%, respectively) than both in group A (0% and 25%, respectively) and in group C (25% and 40%, respectively). A large amount of pericardial effusion was detected in 4 of 5 cases in group B. The incidence of digital necrosis between group A and group B was significantly different (p < 0.05, Fisher's test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493583 TI - [Study of synovial lesions by MRI using gadolinium-DTPA (Gd-DTPA) in patient with early phase of rheumatoid arthritis]. AB - To evaluate the usefulness of magnetic resonance imaging (MRI) enhanced with gadolinium-DTPA (Gd-DTPA) for the detection of the inflamed synovium and for the evaluation of the response to therapy in rheumatoid arthritis, we studied 49 patients with rheumatoid arthritis (RA) according to the 1987 revised criteria of American Rheumatism Association (ARA), 6 patients of systemic lupus erythematosus (SLE) complicated by arthritis, 3 patients of osteoarthritis (OA), 2 patients of Sjogren syndrome, 2 patients of progressive systemic sclerosis and 10 healthy volunteers as an age matched control. The 49 patients with RA were divided into three groups: (1) early phase of RA, (2) non progressing RA and (3) slowly progressing RA, and the stage classification of plain X-ray film and enhancement pattern of MR images were classified into three groups. Synovial enhancement showed a linear, band-like or diffuse pattern. Almost all cases in early phase of RA group and non progressing RA group showed a linear pattern, a band-like pattern or even no enhancement, while slowly progressing group of stage II or higher showed the diffuse pattern of enhancement in all except 2 cases. Moreover, the linear pattern, the band-like pattern or even no contrast enhancement were seen in all except 1 stage I patient, whereas 26 out of 29 patients with stage II or higher change showed diffuse contrast enhancement. Furthermore, a comparison of MR images before and after administration of DMARDs in 10 patients showed that the improvement of clinical symptoms correlated fairly well with reduction of contrast enhancement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493584 TI - [Effect of arthroplasty of the first metatarsophalangeal joint and shortening valgus osteotomy of the first metatarsus on forefoot surgery in rheumatoid arthritis]. AB - Results of forefoot surgery with rheumatoid arthritis were evaluated in 19 feet of 11 patients. Clayton's operation was performed on 12 feet of 7 patients. The follow-up averaged 3 years and 10 months (range, 2 years and 1 month to 8 years). 1 foot (8.3%) recurred hallux valgus deformity and 3 feet (25%) recurred hammer toe deformity. But all patients complained of difficulties to push off action on the forefoot. Interpositional arthroplasty of the first metatarsophalangeal joint with shortening-valgus osteotomy through the first metatarsal base was done on 7 feet of 4 patients. The follow-up averaged 1 years and 8 months (range, 8 months to 2 years and 2 months). 2 feet recurred hammer toe deformity. But, this group had no problem to push off action on the forefoot compared with Clayton's operation. As regard the relief of pain, all patients had satisfactory results from both methods. These results clarified that the preservation for the first metatarsophalangeal joint function was superior for push off action on the forefoot. PMID- 8493585 TI - [A case report--pulmonary cryptococcosis associated with systemic lupus erythematosus and review of 44 cases in Japan]. AB - A case of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) associated with pulmonary cryptococcosis which was successfully treated with fluconazole (FCZ) and flucytosine (5-FC) is described. A 63-year-old woman who had been treated with steroid for SLE and low dose methotrexate (MTX) for RA was admitted to Jichi Medical School Hospital because of abnormal shadow in the chest X-ray film. Physical examination revealed no abnormality. A chest CT film showed multiple nodular shadows localized in the right lower lobe. An ultrasonically guided trans-cutaneous lung biopsy performed on 10th hospital day established a diagnosis of pulmonary cryptococcosis. Following the treatment with FCZ and 5-FC for a month, her abnormal lung shadows improved and serum cryptococcal antigen level was decreased. A survey of the literature from 1955 to 1990 revealed 44 cases of SLE associated with cryptococcosis in Japan, in addition to our case, most of whom were on corticosteroid therapy. The majority of patients were young women, representing the usual population of patients with SLE. 34 of these patients had cryptococcal meningitis; 22, pulmonary cryptococcosis; 6, sepsis; 6 cutaneous cryptococcosis. Twenty patients died. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms. PMID- 8493586 TI - [A case of cyclosporin A-induced myopathy]. AB - A 40-year old man with Behcet's disease was admitted for severe decrease of visual acuity. Since 1987, he had suffered from oral aphtha, retinitis, erythema nodosum, genital ulcer and epididymitis. He was diagnosed as complete Behcet's disease and has been administered cyclosporin A (CYA) and colchicine (Col). Because of repeated ocular attacks and reduced visual acuity, CYA was increased from 3.49 mg/kg/day (220 mg/day) to 6.35 mg/kg/day (400 mg/day) and Col, 0.5 mg/day to 1.0 mg/day. 2 weeks later, he revealed fever, generalized myalgia, muscle weakness and general fatigue, accompanying marked elevation of creatine kinase (4962 IU/l). CYA was discontinued and Col was diminished to 0.5 mg/day. The myalgia disappeared in 4 days and general conditions including creatine kinase were normalized within 2 weeks. We concluded that CYA was highly suspected of the cause of myopathy considering his clinical course. PMID- 8493587 TI - [Three cases of multicentric reticulohistiocytosis with arthritis]. AB - Multicentric reticulohistiocytosis (MR) is a rare systemic disease of unknown origin that is characterized by a proliferation of histiocytes and multinucleated giant cells. Such changes in the synovium can result in a destructive arthritis, although the mechanism of arthritis in MR is poorly understood. In this paper we present three cases of MR with arthritis. In all three cases, articular symptoms preceded to skin lesions. Articular manifestations of MR were similar to those of rheumatoid arthritis; bilateral symmetric involvement, marginal erosions, and severely destructive arthritis in one case. The diagnosis was confirmed by biopsies of the cutaneous nodules and the synovial tissues of the knee joints. A light microscopic examination of the synovial tissue revealed a proliferation of histiocytes with multinucleated giant forms in the synovial stroma. Further, in one case, a proliferation of synoviocytes with a stratification of lining cells and small vessels were found in the synovium. Prednisolone was administered to all cases, though, the responses were not satisfactory. Further investigation about their clinical courses is necessary. PMID- 8493588 TI - [Development of multiple subcutaneous nodules in a patient with rheumatoid arthritis during methotrexate therapy]. AB - A 59-year-old woman with a 14 years' history of seropositive nodular rheumatoid arthritis (RA) who developed multiple subcutaneous nodules during methotrexate therapy was reported. Weekly pulse methotrexate therapy (5-7.5 mg) was initiated in June, 1990 for exacerbation of RA. By January 1991 (total dose of methotrexate: ca 240-310 mg), marked clinical and laboratory improvements were observed. However, subcutaneous which were present prior to methotrexate administration, increased in number and size. The excised nodules showed typical histological features of rheumatoid nodules. The subcutaneous were also characterized by their presence in atypical locations such as the extensor surfaces of finger joints and toes. Recent reports which describe development of subcutaneous nodules and vasculitic lesions in RA patients following methotrexate therapy indicate different pathogenetic mechanisms might be involved in articular disease and nodular lesions. PMID- 8493589 TI - [Immunological aberration in patients with SLE]. PMID- 8493590 TI - [Diagnostic criteria for rheumatoid arthritis and their evaluation]. PMID- 8493591 TI - Central neurocytoma: proliferative assessment by nucleolar organizer region staining. AB - Proliferative potential of four cases of central neurocytoma were assessed by a silver colloid staining technique for argyrophilic protein associated with nucleolar organizer regions (AgNORs). All but one tumor had an Ag-NOR score of less than 2 and were regarded as a benign entity. However, one tumor tissue from a patient suffering from a recurrent central neurocytoma after 13 years from the first operation possessed a 2.06 AgNOR score, which is not significantly different from others. It is considered that central neurocytoma is an essentially benign neoplasm, even though the tumor is recurrent. The present study revealed the usefulness of AgNOR staining for a retrospective assessment of the proliferative potential of central neurocytomas. PMID- 8493592 TI - Spinal cord edema following freezing injury in the rat: relationship between tissue water content and spinal cord blood flow. AB - A spinal cord edema model was developed in the rat by inflicting a freezing injury at -40 degrees C for 3 minutes. Regional spinal cord blood flow, tissue water content, and histology were examined. White matter edema had extended several segments by 8 hours after the injury. Tissue water content increased by 20.6% at 24 hours. Spinal cord blood flow in surrounding tissues decreased by more than 25% 4 hours after the injury. The progression of spinal cord edema following freezing injury appeared to be due to disruption of the blood-spinal cord barrier. PMID- 8493593 TI - Endometrial cancer metastasis to brain: report of two cases and a review of the literature. AB - Two cases of brain metastases from endometrial adenocarcinoma are reported. A 70 year-old female presented with lung metastases 14 months after hysterectomy and adjuvant treatment. At 6 months later, a cerebellar metastasis was resected and followed by radiation therapy. The patient died 5.5 months later. In the second case, a 60-year-old patient developed a lung endometrial metastasis 6 years after initial treatment. At 1 year later she was diagnosed with bilateral hydrocephalus caused by a left temporal and posterior fossa tumor. A ventriculoperitoneal shunt was inserted and she received brain radiation. Two weeks later she gradually became comatose, with right hemiparesis. A metastatic, hemorrhagic temporal tumor was resected but the patient never regained consciousness and died after 7 weeks. The existing literature on brain metastases from endometrial adenocarcinoma is reviewed. PMID- 8493594 TI - Pilocytic cerebellar astrocytoma in adults: case report. AB - A case of cerebellar pilocytic astrocytoma is reported. This tumor occurs typically in the first two decades of life and is seldom reported in adults. The 42-year-old patient presented with occipital headaches, nausea, and unsteady gait. Nystagmus and right dysmetria were noted. A CT scan showed a hypodense, nonenhancing, voluminous, right hemispheric cerebellar cyst. Magnetic resonance imaging showed a nodule in the wall of the cyst which became hyperintense with gadolinium. The mass was resected through a small occipital craniotomy. Neuropathological examination revealed a juvenile pilocytic astrocytoma. PMID- 8493595 TI - Fahr's disease associated with astrocytic proliferation and astrocytoma. AB - This report documents the neuropathological findings of astrocytic proliferation and astrocytoma in a patient with Fahr's disease. At autopsy, there was extensive bilateral symmetrical calcification involving basal ganglia, sulcal depth of the cerebral cortex, and dentate nuclei of the cerebellum. A large low-grade astrocytoma was identified in the left parietal lobe. Astrocytic proliferation was also noted in the areas of early calcification and at the margins of large calcareous deposits, away from the tumor. PMID- 8493596 TI - Correlation between intravascular pressure and risk of hemorrhage due to arteriovenous malformations. AB - The correlation between intraoperative pressure levels measured in the feeding arteries and in the draining veins, and the risk of hemorrhage from arteriovenous malformations (AVMs) is discussed. Feeding artery pressure (FAP) was significantly higher in AVMs with hemorrhage (57 +/- 11 mmHg) than in AVMs without hemorrhage (38 +/- 4), and draining vein pressure (DVP) in the former (24 +/- 5) was significantly higher than that in the latter (13 +/- 5). FAP and DVP were inversely related to the number of draining veins and size of the AVMs. The present study suggests that a high FAP and a high DVP may contribute to the development of hemorrhage from AVMs, and supports previous reports that small AVMs and AVMs with only one draining vein are susceptible to hemorrhage. PMID- 8493597 TI - Pseudotumoral neuro-Behcet's disease. AB - Pseudotumoral presentation of Neuro-Behcet's disease has been described before. The diagnosis may be difficult obtain in patients without mucosal, cutaneous, and ocular signs. We report the observation of a young patient suffering from a right hemiparesis with computed-tomographic (CT) features suggestive of a thalamocapsular expanding lesion. Histologic study of brain biopsy tissue ruled out a tumor but did not show any specific diagnosis. The patient improved with steroid therapy. PMID- 8493598 TI - Primary multiple hydatid cysts of the brain: case report. AB - Primary multiple hydatid cyst in the brain is uncommon. We report two large primary multiple hydatid cysts of the brain in an adult, which were removed without rupture by two separate operations. PMID- 8493599 TI - Spontaneous regression of intracranial arteriovenous malformation. AB - Spontaneous regression of an arteriovenous malformation is rare. When complete or partial regression occurs, an associated factor is usually involved, such as intracranial hemorrhage, surgery, radiation therapy, or a new neurological deficit. Another case in which the resolution was totally spontaneous is presented here. We discuss the importance of transcranial doppler revealing the hemodynamic changes in the cerebral arteries in the presence of an AVM and when the latter is thrombosed. Several mechanisms for regression are considered, and we focus on the dissection of the afferent vessel, pointing out the role of such an event in the natural history of AVM. PMID- 8493600 TI - Transcranial Doppler changes during staged surgical resection of cerebral arteriovenous malformations: a report of three cases. AB - The removal of large arteriovenous malformations (AVMs) in stages has been advocated to reduce the risk of perioperative hyperemic complications. In three patients who had a two-stage surgical removal of their large (> 6 cm) frontal AVMs, transcranial Doppler (TCD) was performed 1 day before and 1 day after each surgery. Arteries still feeding the AVM after the first procedure had an increase in mean velocity (MV) and a decrease in the pulsatility index (PI) in the period between the two surgeries. MV reactivity to carbon dioxide before each stage was higher in feeding arteries at the second surgery, suggesting that the total magnitude of the shunt through the AVM was lower in spite of flow recruitment. TCD can be used to monitor the hemodynamic changes after embolization or partial surgery and may be of help in better defining the optimal time for final resection. PMID- 8493601 TI - Motor-evoked potential changes during hypoxic hypoxia. AB - Motor-evoked potentials (MEPs) from forearm muscles were recorded in response to single-shock electrical stimulation of motor cortex of rats (n = 15) under pentobarbital anesthesia and controlled room air ventilation. In addition, electroencephalograms (EEGs) were recorded for all animals. Following baseline MEP recording in room air (21% O2), animals were subjected to graded hypoxia of either 15.75%, 10.5%, or 5.25% oxygen for 10 minutes, then followed by room air ventilation for 15 minutes. The mean baseline latency, amplitude, and duration of the evoked muscle response were 4.3 +/- 0.4 mseconds, 556 +/- 476 microV, and 9.6 +/- 2.3 mseconds, respectively. At moderate hypoxia (15.75%), the latency was 4.2 +/- 0.5 mseconds and the amplitude and the duration were 530 +/- 356 microV (n = 14), and 9.5 +/- 2.2 mseconds, (n = 14). These values did not deviate significantly from baseline (p > 0.56). Only one animal lost MEPs at the 15.75% hypoxia level. At 10.5% hypoxia, 27% of animals (n = 4) lost MEP within minutes. In the remaining animals (n = 11), there was a trend toward a prolongation of latency and a decrease of both amplitude and duration. All animals lost MEPs under extreme hypoxia (5.25%) within 2 minutes. No change was seen in the EEG recording until the level of extreme hypoxia was reached. The loss of MEPs at this level of hypoxia was concurrent with the loss of EEGs. We conclude that hypoxia effects MEPs in experimental animals. PMID- 8493602 TI - Evaluation of the calcium channel antagonist nimodipine after experimental spinal cord injury. AB - The cortical somatosensory evoked potentials (CSEPs) were recorded to determine if the administration of nimodipine improves axonal function after spinal cord injury. Animals receiving a 52 g compression injury (a moderately severe injury) for 5 minutes were randomly allocated to one of five treatment groups. Each group was given an infusion of one of the following nimodipine regiments over 2 hours, commencing 1 hour before compression: placebo (n = 20), 0.5 micrograms/kg (n = 10), 0.25 micrograms/kg (n = 20), 0.125 micrograms/kg (n = 10), and 0.25 micrograms/kg + Hetstarch (n = 10). In the control group, 65% of animals lost the CSEPs immediately after the injury with almost all (95%) of these regaining the CSEPs within 15 minutes after decompression of the spinal cord. In the treated groups, the rate of the CSEP loss was highest in the 0.5 micrograms/kg group. This group also had the lowest CSEP recovery. The proportion of the CSEP loss was essentially the same for the other nimodipine-treated groups, although it seemed that there was an increasing number of nonresponses with increasing the nimodipine dose. Our data indicate lack of any beneficial effects of nimodipine on axonal function as measured by evoked activities in experimental spinal cord injury. PMID- 8493603 TI - [Benjamin's mother. Interview by Anne Vesterdal]. PMID- 8493604 TI - [Ethics. 50% chance]. PMID- 8493606 TI - [Acute crisis intervention in fatal accidents]. PMID- 8493605 TI - [Informatics--a common language]. PMID- 8493607 TI - [Quality control. A quality administrator at the head]. PMID- 8493608 TI - [UNICEF--the vulnerable years]. PMID- 8493609 TI - [Nursing care--a conical section]. PMID- 8493610 TI - [Our employers are on a collision course. Interview by Soren Palsbo]. PMID- 8493611 TI - [Benjamin]. PMID- 8493612 TI - [Portugal: no money]. PMID- 8493613 TI - [Portugal: out of bed]. PMID- 8493614 TI - [Portugal: exhausted 40-year-olds]. PMID- 8493616 TI - [Nursing stories. Rubber word gets content]. PMID- 8493615 TI - [Self help--living with breast cancer]. PMID- 8493617 TI - [Executive Board]. PMID- 8493618 TI - [Portugal: another bed for Lidia]. PMID- 8493619 TI - [Portugal: specialist in rehabilitation]. PMID- 8493620 TI - Nocturnal asthma. PMID- 8493621 TI - Mediator and cytokine mechanisms in asthma. PMID- 8493622 TI - Diagnostic rigid and flexible oesophagoscopy in carcinoma of the oesophagus: a comparison. AB - BACKGROUND: Flexible oesophagoscopy is regarded as superior to rigid oesophagoscopy on the basis of perforation rates as an end point. This advantage may be more apparent than real because no comparison has been made in a diagnostic setting in patients with carcinoma of the oesophagus with both perforation rate and diagnostic efficacy as indices. METHODS: A retrospective analysis was carried out on data on 336 diagnostic oesophagoscopies in patients with carcinoma of the oesophagus, comparing rigid with flexible oesophagoscopy. RESULTS: Both rigid and flexible oesophagoscopies were performed without perforation when they were used for diagnosis only. Rigid biopsy achieved a diagnostic success rate of 99.3%, compared with 80.5% for flexible oesophagoscopy. CONCLUSIONS: Diagnostic oesophagoscopy can be achieved without perforation with either instrument, but the chance of diagnosing carcinoma was significantly greater with the rigid instrument. PMID- 8493623 TI - Influence of smoking habits on change in carbon monoxide transfer factor over 10 years in middle aged men. AB - BACKGROUND: Emphysema is associated with a reduction in carbon monoxide transfer coefficient (TLCO/VA), but little is known about the evolution of changes in TLCO/VA in middle aged smokers at risk of developing chronic airflow obstruction. METHODS: TLCO/VA (single breath method) was measured on two occasions 10 years apart in 122 middle aged men. RESULTS: Initially TLCO/VA averaged 97% predicted in never smokers (n = 42, mean age 37.2 years), 99% predicted in ex-smokers (n = 21, mean age 41.9 years), and 85% predicted in those who smoked over 15 cigarettes a day (n = 42, mean age 42.0 years). Mean rates of decrease in TLCO/VA over 10 years, however, were similar in the three groups, so that differences between smokers and non-smokers did not increase during the 10 years. Seventeen men (mean age 40.9 years) who initially were smokers became sustained ex-smokers within two years of the first measurement; in these men mean absolute values of TLCO/VA rose, averaging 89% predicted at the first assessment but 102% predicted 10 years later. CONCLUSION: By the age of about 40 years TLCO/VA was lower in smokers than in never smokers but this difference did not increase over the following 10 years. Sustained ex-smokers had values similar to those of never smokers even when TLCO/VA was known to have been reduced while they were smoking. Changes in TLCO/VA associated with stopping smoking were considerably larger than could be explained by carbon monoxide back pressure, indicating that mechanisms other than irreversible increase in the size of terminal air spaces underlie the lower values in smokers. To detect emphysema in smokers it is necessary to use reference equations that take account of current smoking. PMID- 8493624 TI - Arousal responses to added inspiratory resistance during REM and non-REM sleep in normal subjects. AB - BACKGROUND: Arousal in response to increased airflow resistance during sleep, especially rapid eye movement sleep (REM), could be an important protective mechanism against asphyxia. METHODS: The arousal response to the application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in ten healthy men. RESULTS: The number of arousals occurring within two minutes of the load application was significantly higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4, and was similar to that during stage 1. The proportion of arousals to non-arousals decreased significantly from stage 1 to stage 4. The mean time to arousal in REM was significantly shorter than in non-REM stages 1, 2 or 3/4 and increased significantly from stage 1 to stage 3/4. The duration of sleep (comparing the results of the first with the second half of the sleep period time) did not modify the arousal response in stages 2 and 3/4. CONCLUSIONS: The results show a significantly increased arousal response to an added inspiratory resistive load in REM sleep compared with non-REM sleep stages 2, 3 or 4 in normal men. In the context of previous studies these data could add support to the hypothesis that the decreased arousal response during REM sleep in patients with sleep apnoea might be due to an impairment of the normal "central processing" of this stimulus. PMID- 8493625 TI - Effect of an oral potassium channel activator, BRL 38227, on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol. AB - BACKGROUND: Potassium (K+) channel activators, such as cromakalim, open ATP sensitive K+ channels and relax airway smooth muscle in vitro and inhibit induced bronchoconstriction in vivo in animals. The prolonged half life of cromakalim gives it potential as an oral bronchodilator. The effect of orally administered BRL 38227 (the active enantiomer of cromakalim), at doses of 0.125, 0.25, and 0.5 mg, on airway function and airway responsiveness to histamine and methacholine has been investigated in asthmatic patients. METHODS: Seventeen patients with asthma were studied in three separate randomised double blind, placebo controlled studies. In the first study eight patients with moderately severe asthma were given 0.125, 0.25, and 0.5 mg of BRL 38227 or placebo, and responses to histamine were assessed before and five hours after treatment. In the second study responses to methacholine were measured before and five hours after 0.125 and 0.5 mg of BRL 38227 or placebo were given to nine patients with mild asthma. In the third study the effect of 0.5 mg of BRL 38227 or placebo was assessed in eight patients with mild asthma. Responses to histamine were measured before treatment and two and five hours after treatment. To provide a positive control study eight subjects who had taken part in studies 1 and 3 were also given oral salbutamol (8 mg) in a placebo controlled, double blind study. Responses to histamine were assessed before and two hours after treatment. RESULTS: BRL 38227 did not cause significant bronchodilatation or changes in airway responsiveness in any of the studies. Headache was reported in 19 of 25 of patients receiving (in some cases twice) 0.5 mg of BRL 38227. By contrast, oral salbutamol gave significant protection against histamine challenge (geometric mean 2.23 doubling dilutions). CONCLUSIONS: After a single oral dose of BRL 38227 no beneficial effect on airway function was detected, despite a high incidence of side effects, which indicates that the orally administered K+ channel activator BRL 38227 may not be useful in the management of asthma. PMID- 8493626 TI - Regular inhaled beta agonist in asthma: effects on exacerbations and lung function. AB - BACKGROUND: A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported. This paper presents additional information on exacerbations of asthma and trends in lung function, airways hyperresponsiveness to methacholine, and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment. METHODS: Subjects undertook a year long randomised, double blind crossover study of regular upsilon as needed inhaled beta agonist treatment. Fenoterol (400 micrograms) or matching placebo was inhaled as a dry powder four times daily for 24 weeks, then subjects crossed over to the alternative regimen. Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study. Symptoms, peak expiratory flow rates, and drug use were recorded daily, spirometry was performed every four weeks, and methacholine and bronchodilator responsiveness were measured every eight weeks. RESULTS: Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment. Prebronchodilator forced expiratory volume in one second (FEV1) was on average 0.15 litres lower (95% confidence interval (95% CI) 0.11-0.19) and vital capacity (VC) 0.12 litres lower (95% CI 0.08-0.16) than during the placebo period. Morning peak flow rates were significantly lower and evening peak flow rates significantly higher, with an increase in diurnal variation from 9.8% (95% CI 6.9 12.8) to 17.5% (95% CI 13.8-21.3) during regular treatment. Geometric mean concentration of methacholine causing a 20% fall in FEV1 from the value after saline (PC20) decreased significantly from 1.63 to 1.15 mg/ml, indicating increased bronchial hyperresponsiveness during regular treatment. Response to bronchodilator, as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1, was maintained with no evidence for tachyphylaxis. CONCLUSION: Chronic use of inhaled fenoterol resulted in more exacerbations, a significant decline in baseline lung function, and an increase in airway responsiveness to methacholine in asthmatic subjects, but did not alter bronchodilator responsiveness. These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma. PMID- 8493627 TI - Total population survey of the frequency and severity of asthma in 17 year old boys in an urban area in Israel. AB - BACKGROUND: There is evidence that the prevalence of asthma in children and young people is increasing. METHODS: An examination of a total population (35,170) of 17 year old Jewish boys of one seaside urban area in Israel was undertaken during two years, 1986 and 1990, by trained respiratory physicians in a regional recruiting office of the Israel Defence Forces. All boys who had ever been diagnosed as having asthma or symptoms that could have been due to asthma underwent a further examination by respiratory physicians that included spirometry at rest. A test to evaluate exercise induced asthma was performed on a treadmill in 88% of the boys. RESULTS: Lifetime prevalence (asthma in the past or at present) increased from 7.9% in 1986 to 9.6% in 1990. Point prevalence (current asthma) increased from 5.0% to 5.9%. The prevalence of current asthma increased in all degrees of severity (mild disease from 3.3% to 3.7%, moderate disease from 1.7% to 2.2%, and severe disease from 0.03% to 0.04%). By the age of 17, 77.4% of boys who had suffered from asthma had no or only very mild symptoms. CONCLUSIONS: It is considered that the measured increase in prevalence of asthma from 1986 to 1990 reflects a true increase among the Jewish Israeli population. PMID- 8493628 TI - Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity. AB - BACKGROUND: Conflicting views exist over whether responsiveness of the airways to hypertonic saline relates to non-specific bronchial hyperresponsiveness measured by histamine or methacholine challenge. The bronchoconstrictor responses to exercise and hypertonic saline are reported to be closely related, but the relationship between the symptoms of exercise induced asthma and airway responsiveness to hypertonic saline is not known. METHODS: In 29 asthmatic patients with a history of exercise induced asthma, the response to an ultrasonically nebulised hypertonic saline (3.6% sodium chloride) aerosol, measured as the volume of hypertonic saline laden air required to produce a fall in forced expiratory volume in one second (FEV1) of > or = 20% (PD20), was compared with the concentration of histamine (PC20; group 1) and methacholine (PC20; group 2) producing a 20% fall in baseline FEV1 and exercise induced asthma symptom severity score (groups 1 and 2). The hypertonic responsiveness was determined in a dose-response manner to a maximum dose of 310 1 and the exercise induced asthma symptom severity was scored on a scale of 0-5. RESULTS: Of the 29 patients, 23 (79%) were responsive to the hypertonic saline, with PD20 values ranging from 9 to 310 1. A significant correlation was found between the PD20 hypertonic saline and the exercise induced asthma symptom score. There was no significant correlation between the PD20 response to hypertonic saline and the histamine PC20 or methacholine PC20. The exclusion of those subjects who failed to respond to hypertonic saline improved the relationship between hypertonic saline and methacholine PC20. No significant correlation was found between the exercise induced asthma symptom score and histamine PC20 or methacholine PC20. CONCLUSION: These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity. PMID- 8493629 TI - Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group. AB - BACKGROUND: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months. METHODS: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period. RESULTS: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study. CONCLUSIONS: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma. PMID- 8493630 TI - Pulmonary deposition of a nebulised aerosol during mechanical ventilation. AB - BACKGROUND: There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. METHODS: Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. RESULTS: Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). CONCLUSIONS: Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients. PMID- 8493631 TI - Rapid detection of pneumococcal antigen in pleural fluid of patients with community acquired pneumonia. AB - BACKGROUND: Detection of pneumococcal antigen may help to increase the rate of diagnosis of pneumococcal pneumonia. This study was designed to determine the value of rapid detection of pneumococcal antigen in pleural fluid from patients with community acquired pneumonia. METHODS: Thoracentesis was performed in patients suspected of having empyema and in patients with pneumonia of unknown aetiology. Pneumococcal capsular antigen was detected by latex agglutination and this method was compared with Gram staining and culture, specimens of pleural fluid being examined in parallel by the three methods. RESULTS: Pleural fluid was radiographically identified in 63 of 135 patients with community acquired pneumonia. In nine of 45 patients with pneumococcal pneumonia and pleural fluid pneumococci were identified by Gram stain in two and by culture in one specimen of pleural fluid, whereas antigen was detected in eight of these specimens. In 12 of 33 patients with pneumonia of other known aetiology only one pleural fluid specimen was antigen positive, providing a specificity of 92% for this test. Pleural fluid obtained from 12 of 58 patients with pneumonia of unknown aetiology yielded detectable antigen in seven cases. CONCLUSIONS: Detection of pneumococcal antigen by latex agglutination in pleural fluid may yield important and rapid information in patients with community acquired pneumonia. PMID- 8493632 TI - Peak expiratory flow in rural residents of Tamil Nadu, India. AB - BACKGROUND: In a country such as India that covers several latitudes, climatic zones, ethnic groups, and dietary habits lung function within the normal population would be expected to vary. Several studies have looked at normal values of peak expiratory flow (PEF) in different regions of urban India but none has looked at rural South India. A study of PEF has now been carried out in a rural population of Tamil Nadu. METHODS: All subjects were of Dravidian stock and lived at sea level with rice as their staple food. Ten five year age groups from 10 to 59 years with 100 males and 100 females in each were studied. Peak flow was measured by mini-Wright peak flow meter, and height was also measured. Regression equations for predicting normal PEF were calculated. RESULTS: Peak flow ranged from 150 to 680 l/min in males and from 150 to 500 l/min in females. Maximum values of PEF were attained at the age of 32.5 years in men and 35.6 years in women. There was a significant linear correlation between height and PEF and a curvilinear relation between age and PEF in both sexes. CONCLUSION: Regression equations are now available for PEF values in normal subjects from rural South India. PEF was related to age and height and values were greatest in the fourth decade. PMID- 8493633 TI - Ultrasound guided aspiration biopsy for pulmonary tuberculosis with unusual radiographic appearances. AB - BACKGROUND: Pulmonary tuberculosis can produce unusual radiographic appearances and negative results of sputum and bronchoscopic examinations are common. This study assessed the value of ultrasound guided aspiration biopsy in the diagnosis of pulmonary tuberculosis with unusual radiographic appearances. METHODS: Thirteen patients, ultimately diagnosed as having tuberculosis, underwent a chest ultrasonographic examination between June 1984 and August 1991. All had sputum available for examination and nine were also examined by bronchoscopy. Ten patients who had a negative sputum smear and negative bronchoscopic brushing smears underwent ultrasound guided aspiration or biopsy. Percutaneous aspiration was performed with a 22 gauge needle. If the smear did not reveal acid fast bacilli, a biopsy sample was taken with a 16 gauge Tru-cut needle to obtain a histological diagnosis. RESULTS: The ultrasonographic examination delineated the more complex nature of the lesions better than the chest radiograph. Ultrasound guided aspiration biopsy provided the diagnosis in nine of 10 patients, while the sputum smear and culture provided diagnosis in five of 13, and bronchoscopy in four of nine. In terms of rapid diagnosis, ultrasound guided aspiration biopsy gave the diagnosis in eight of 10 cases. No patient developed a major complication. CONCLUSION: Ultrasonography can direct the needle to the most suitable part of a lesion to obtain the relevant specimens. The diagnostic yield is high and the procedure is relatively safe. It is especially helpful in patients with negative results of sputum and bronchoscopic examinations. PMID- 8493634 TI - Pulmonary alveolar microlithiasis: review of Turkish reports. AB - Pulmonary alveolar microlithiasis is a rare disorder, only 173 cases having been reported worldwide. Fifty two cases from Turkey are reported, 49 of which have previously been described only in Turkish publications. The mean age of the patients was 27 (SD 12) years, 34 were male, and 10 were symptomless. In 40 of the 52 cases diagnosis was confirmed histopathologically. Nineteen cases were diagnosed in siblings. This high rate suggests that pulmonary alveolar microlithiasis is a familial disease, which, though rare, is for unknown reasons most common in Turkey. PMID- 8493635 TI - Attitudes to smoking and smoking habits among hospital staff. AB - BACKGROUND: Health professionals should take an active role against smoking, so it is relevant to have information on their smoking habits and their attitudes towards smoking, especially with a view to identifying and offering help to those smokers who wish to stop. Staff in Llandough Hospital were surveyed to determine their smoking habits and attitudes, and the findings were compared with those of a similar survey at Llandough in 1987. METHODS: In October 1991 a questionnaire was sent to each member of staff employed half time or more requesting data on age, sex, department, smoking habit, attitudes to smoking in various areas of the hospital, and attitudes to access to smoking rest rooms for patients, staff, and visitors. Smokers were asked whether they would like to join a "quit smoking" group. Non-responders were sent a reminder four weeks later and all replies returned by 31 December 1991 were analysed. RESULTS: The response rate was 82%; of the respondents, 65% were non-smokers, 15% ex-smokers, and 20% current smokers. The prevalence of current smokers was 5% among doctors, 20% among nurses, 18% among administrative and clerical staff, and 40-42% among domestics, catering, and portering staff. Thirty eight per cent of responders wished smoking to be completely forbidden in all areas of the hospital and 90% in certain areas such as wards, offices, cafeteria, and laboratories. Nearly half wanted smoking to be allowed in rest rooms and over 60% wanted a 24 hour facility for smoking for staff, 56% for patients, and 44% for visitors. Only 39% of smokers wished to join a "quit smoking" support group. In comparison with the 1987 survey, the response rate in this study was higher (82% v 70%), the proportion of non-smokers had increased (65% v 59%), and more smokers wanted help (39% v 26%). Fewer wanted 24 hour access to smoking areas for staff and for visitors. CONCLUSION: This hospital should capitalise on these changes of attitude among staff and proceed more rapidly with the implementation of policies to further reduce smoking among staff, visitors, and patients. As a first step a smoking cessation counsellor has been appointed. PMID- 8493636 TI - New perspectives on basic mechanisms in lung disease. 3. Drug intervention in asthma: present and future. PMID- 8493637 TI - Bronchial rupture secondary to blunt chest trauma. AB - Bronchial injury due to blunt chest trauma is rare, and its rarity and the fact that it has two distinct modes of presentation may considerably delay diagnosis. Two recent cases illustrate the two main types of injury and presentation. In the first the rupture is intrapleural and air escapes into the pleural space; insertion of a chest drain leads to a continuous air leak. In the second type the rupture is largely extrapleural with little communication with the pleural cavity; initially symptoms may be mild or absent but complications may occur later. PMID- 8493638 TI - Primary malignant melanoma of the oesophagus with a left atrial metastasis. AB - A 75 year old man with an eight month history of dysphagia and weight loss underwent pericardiocentesis for a massive pericardial effusion. The echocardiogram showed a mass in the left atrium, and computed tomography also showed distal oesophageal narrowing, which was found to be due to a malignant melanoma. The left atrial mass, investigated by immunoscintigraphy with technetium-99m labelled monoclonal antibody, was diagnosed as metastatic melanoma. This represents a rare case of primary oesophageal melanoma with left atrial metastasis. PMID- 8493639 TI - Diverticulosis of the main bronchi: a rare cause of recurrent bronchopneumonia in a child. AB - Diverticulosis of the main bronchi, not associated with other organ abnormalities, developed in a 12 year old child. This abnormality caused recurrent bronchopneumonia in the lung with the main bronchi diverticulosis. Fibreoptic bronchoscopy helped to locate the lesion and selective bronchography, with injection of contrast medium through the suction channel of the fibreoptic bronchoscope, showed the morphology of this rare malformation. PMID- 8493640 TI - Broncho-oesophageal fistula treated effectively without surgical resection. PMID- 8493641 TI - Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis. PMID- 8493642 TI - New perspectives in Wegener's granulomatosis. PMID- 8493643 TI - [Sick-listing and rehabilitation]. PMID- 8493644 TI - [EDP in primary health care]. PMID- 8493645 TI - [Contact tracing in sexually transmitted diseases--medically important and ethically correct]. PMID- 8493646 TI - [Quality assurance in obstetric practice]. PMID- 8493647 TI - [Surgical delivery in Norway during the last 20 years--analysis of great changes]. AB - In Norway, the frequency of deliveries by cesarean section rose from 2.0% to 12.6% between 1968 and 1990. During the same period vaginal births of foetuses in breech presentation decreased by about 50%. All types of operative delivery were more common among women giving birth for the first time than among those who had given birth previously. Throughout the twenty years of our study the highest frequency of operative delivery was found in the health region comprising Oslo and the counties of Hedmark and Oppland in the eastern part of Norway. But the difference in relation to the other regions diminished toward the end of the 1980s. When university clinics were compared with non-university departments, we found that the frequencies were 2.0 to 2.5 percentage points higher at the former throughout the study period, again with a tendency toward less difference in the most recent years. With few exceptions, the frequency of cesarean section was positively correlated to the annual number of births in the departments. Already in 1970-71 cesarean section was performed on more than one fourth of the para 0 mothers aged 35 and above. This frequency rose to 40% in 1984-86, and then dropped to 35% in 1989-90. The most striking trend in cesarean section practice was noted for low birth weight, with a dramatic increase for birth weights below 2,500 g. While birth weight-specific cesarean section rates differed little along the weight scale in 1970-71, in the years 1989-90, 67% of the births weighing between 1,000 and 1,499 g in 1989-90 were delivered by cesarean section. PMID- 8493648 TI - [Infections after cesarean section]. AB - Post-operative infectious morbidity was recorded in 390 patients who delivered by Caesarean section. The patients were observed closely while in hospital. Upon leaving the hospital, each was given a questionnaire, which was answered by 350 (89.7%). 10% of the patients had experienced post-operative infections, the most frequent being infections of the urinary tract or of wounds. There was no significant difference in post-operative infectious morbidity in the case of elective as against emergency Caesarean section. This may have been due to the use of prophylactic antibiotics in many cases of emergency Caesarean section. Only 28.6% of the infections were diagnosed during hospitalization. Therefore, many infections following Caesarean section are diagnosed after the patient has been discharged from hospital. PMID- 8493649 TI - [Contact tracing of genital Chlamydia infection]. AB - The present study evaluates two strategies for partner notification among young women with genital Chlamydia trachomatis infection. The study included 443 women, aged 14-21 years, who visited one of 20 youth clinics during a two months period in 1991. The youth clinics were randomized to use patient referral or provider referral. In the latter group, 11 of 14 women with genital Chlamydia infection revealed their sexual partners. Only five of 24 sexual partners were notified by a letter, and six of 24 partners turned up for examination. In the patient referral group, 16 of 34 women asked to notify their partner, and ten of 31 partners were examined. Partner notification in young women with genital Chlamydia infection seems to be difficult. PMID- 8493650 TI - [Experiences of pregnant women with information procedures in routine ultrasound examinations]. AB - A national representative sample of 891 healthy women answered a questionnaire on the information provided about the routine ultrasound examination around the 17th week of pregnancy. Of 888 women 456 (51%) women stated that they had not received any form of information before the ultrasound examination. If a pregnant woman is supposed to make the decision about whether to have a prenatal ultrasound scan done or not, she must have specific information to enable her to do so. The fact that a large percentage of the women were not aware that the ultrasound examination is not compulsory denies them the right to make an autonomous decision. PMID- 8493651 TI - [Capnography. A new monitoring method may improve patient safety during anesthesia and in the recovery room]. AB - This review describes the diagnostic possibilities of capnography: the graphic presentation of carbon dioxide concentrations in respiratory gas during the entire respiratory cyclus. The monitoring may confirm that the tube used for intubating the patient's trachea is positioned in the patient's airway, and indicates dysfunction of the tube or of the ventilator. Capnography can also rapidly provide important information about a patient's ventilation, circulation and metabolism. This may improve patient safety during anaesthesia and in the intensive care unit. Patients without artificial airways may also be monitored by capnography. The method may reduce the number of arterial blood gases required to check the degree of ventilation. PMID- 8493652 TI - [Endocrine disorders in adolescents and young adults]. AB - Evaluation of 158 patients younger than 25 years-of-age who had been hospitalized in a specialized adult endocrine department during an 11 year-period, brought to light specific endocrine problems connected both to pediatrics and internal medicine. There is need for close collaboration between pediatricians, as experts on disturbances in growth and pubertal development, and internists, with experience of diagnosing rare endocrinological disorders. Such collaboration might also improve the follow-up of young patients into adulthood. PMID- 8493653 TI - [The significance of radiologically diagnosed brain concussion for the outcome after head injury]. AB - The early and late outcome was evaluated in head injury patients who presented brain contusion(s) on the cranial CT scan and in patients hospitalized for concussion. There was a high degree of concurrence between mortality and CT findings. Late complaints were common among cases of concussion of the brain. However, the frequency of impaired memory and concentration, speech problems, paresis and epileptic seizures was increased in cases where the CT scan showed brain contusion. Adaptive and social functioning was most impaired in cases with multifocal contusions in both hemispheres. PMID- 8493654 TI - [Pleuropulmonary actinomycosis]. AB - A previously healthy 42 years old male was admitted to hospital with chest pain. Chest radiograms revealed a solid mass in the left thoracic cavity. A lung biopsy showed findings consistent with probable actinomycosis. It was feared that the specimen was not representative and a left upper lobe lobectomy was performed. This confirmed the diagnosis of actinomycosis. The patient was postoperatively treated with penicillin and tetracycline and has remained well during a follow-up period of two years. PMID- 8493655 TI - [Partial gangrene of the scrotum and penis. A complication of sclerotherapy of testicular hydrocele]. AB - Localized gangrene of the scrotum and penis as a complication to tetracycline sclerotherapy for hydrocele has not been reported before. I describe the complication in a 56 year-old man who was admitted to our plastic surgery unit for excision and reconstruction four days after sclerotherapy. The procedure of tapping and injection, and how to avoid this type of complication, are discussed. PMID- 8493656 TI - [Microductectomy. A simple method for excision of intraductal changes in the breast]. AB - Next to tumour and pain, discharge from the nipples is the most common reason for remitting women to a breast clinic, and comprises 3-6% of the total cause of remittance. We describe a technique for localizing a duct system, where a defect is found by galactography by injection of methylenblue/Isopaque Amin 1:1 in the duct system prior to operation. Ultrasonography can be used to localize the ectatic ducts in cases where there is no secretion on the day of the scheduled operation. The blue colour enables the surgeon to excise the defect duct very precisely. Such a microductectomy preserves breast tissue and gives a better cosmetic result than with complete central ductectomy. We discuss examination and treatment of women with discharge from the nipple. PMID- 8493657 TI - [Automatic data processing in primary health care]. AB - Norwegian general practitioners are installing computers in their offices at an increasing rate. More than half of them now run their practice using electronic journals and electronic exchange of information with hospitals, pharmacies etc. There is wide interest among colleagues in the development of new software approaches and packages for running the office. At present, this development is marked by creativity and competitiveness. In fact, Norway has become a market leader within GP-software exporting as far as to Australia. In this article, the seven packages currently available are described by experienced users, and compared from a technical point of view. PMID- 8493658 TI - [Standardization of medical forms in health care]. AB - In the Norwegian health care system, resources worth several 100 millions of US dollars are tied up in traditional routines for handling forms. A standard form, combined with computer record systems, could potentially release a considerable share of these resources for alternative uses. Universal Form Medicine (UFM) has been used by Norwegian general practitioners since 1985. The Universal Form Medicine has been a stable standard, and replaces more than 95% of all health forms. Today, about 50% of all doctors with a computerized medical record system can use this standard form. From most aspects, the Universal Form Medicine has advantages over preprinted forms, and can be adapted to silent printers. To our knowledge, no other countries have taken the advantage of standardizing their medical forms. PMID- 8493659 TI - [Acetylsalicylic acid and pre-eclampsia/growth retardation]. PMID- 8493661 TI - [The elderly and automobile driving]. PMID- 8493660 TI - [Jehovah's Witnesses and progress within transfusion medicine]. PMID- 8493662 TI - [The silent knowledge. An intermediary of values in the medical education]. PMID- 8493663 TI - [Failing laboratory service is the worst deficiency disease in Africa]. PMID- 8493664 TI - [Prioritization--medicine or economics?]. PMID- 8493665 TI - [Compliance--a problematic concept]. PMID- 8493666 TI - [Tuberculosis]. PMID- 8493667 TI - [Openness with cancer patients]. PMID- 8493668 TI - [Attitudes to acupuncture--a questionnaire study among medical students in Tromso]. AB - In February 1992, 80% of the medical students at Tromso University filled in a questionnaire concerning attitudes to acupuncture. 63% of the students would recommend acupuncture when the diagnosis was migraine, while 14% of the students would support a patient who tried acupuncture as cancer therapy. 86% of the students thought that placebo could account for 25-50% of the effect of acupuncture. Most of the students wanted more scientific documentation, although 75% said that acupuncture already was, or at least should be, part of the ordinary health care system. The main result of this study was a generally positive attitude towards acupuncture. The students want to learn the method, and they will recommend acupuncture for their future patients. PMID- 8493669 TI - [Mistletoe in the treatment of cancer]. AB - Mistletoe (Viscum album) was introduced in the treatment of cancer in 1917. Today, extracts from the plant are used in adjuvant cancer therapy mainly as injections. The most important active agents are lectins, which have cytotoxic and immunostimulating effects. Mistletoe extracts have low toxicity. No fatal side effects have been reported. More than 40 clinical studies have been carried out, mainly at the Lukas Klinik in Switzerland and the Ludvig Boltzmann-Institute in Austria. Most of these studies claim that mistletoe has a positive effect, but were of poor methodological design. Therefore, in the light of our own positive experiences, we recommend a randomized multicentre study to evaluate the effect of mistletoe in cancer treatment. PMID- 8493670 TI - [Significance of mycotoxins for health--present and past]. AB - Investigations from several European countries indicate that, in former days, there was a connection between mycotoxins, mortality and reduced birth rate. In addition to being acutely toxic, many mycotoxins can interfere with the immune system, even in small concentrations. While tuberculosis was declining in Norway as a whole around year 1900, it culminated in Finnmark county. In addition, infant mortality was high. These people in the North ate rye flour imported from Russia, and harvested, transported and stored under conditions which may have favoured growth of toxic fungi. The mycotoxin ochratoxin A has been surveyed in several countries. The level in human sera seems to indicate continuous, widespread exposure of humans to ochratoxin A. Mycotoxin contamination of food and feeds may be a health problem of unknown dimensions. PMID- 8493671 TI - [Abdominal tuberculosis and amebic abscess. Simultaneous diagnosis of 2 rare infections of same localization]. AB - A 26-year-old Indian male was admitted to hospital with loss of weight and vague abdominal pain of several weeks duration. Ultrasonography and computed tomography showed several expansive lesions near the pancreatic head, probably representing enlarged lymph nodes. A few milliliters of yellowish pus were aspirated by ultrasound guided aspiration. Microscopic examination of the pus showed trophozoits, and Mycobacterium tuberculosis subsequently grew from the pus culture. Abdominal tuberculosis is a rare condition, particularly in the pancreas and the peripancreatic region. The report stresses the importance of considering the possible coexistence of more than one infectious disease in patients from endemic areas. PMID- 8493672 TI - [Male genital tuberculosis]. AB - AIM: To describe symptoms and clinical findings in patients with extrapulmonary tuberculosis and to draw attention to the fact that the disease still exists in spite of the declining incidence of pulmonary tuberculosis. DESIGN: Retrospective data from hospital records and the Register of Tuberculosis in Funen, Denmark from 1976 to 1991. REGIMEN: The investigation was carried out at the Department of Urology and the Department of Internal Medicine, Pneumology Section, Odense University Hospital, Denmark. MATERIAL: Eight patients with genital tuberculosis during a period of 15 years in Funen Island. RESULTS: Genital tuberculosis in males involves especially the epididymis, and the most frequent symptom is a painful swelling of the testicles. The average age of the patients was 62 years. PMID- 8493673 TI - [Doping and doping control in Norway]. AB - Misuse of drugs and methods of doping in connection with various physical activities have become serious problems for sports organizations and may seriously impair the health of the misusers. The Norwegian Confederation of Sports has banned doping, and carries out doping controls at competitions as well as out-of-competition tests. Doping controls and laboratory analyses are performed according to approved procedures. An athlete who is found guilty of doping will be excluded from organized sport for a specified period of time. Doctors have a special duty to keep themselves updated on the doping problem, and support the anti-doping work by their own practices. PMID- 8493674 TI - [Dilemmas in sports medicine--a medical challenge]. AB - The theme of the article is ethical problems and dilemmas in sports medicine. Our practice should be guided by medical norms and rules and the fair play-norm of sport. International and national examples are presented and used to elucidate some dilemmas. A special problem for the doctor may be loyalty to the team and to the coach. Use of drugs can be a temptation for doctor as well as for athlete. Misuse of athletes as experimental subjects has been a problem in some countries. PMID- 8493675 TI - [The Board of Health and its activities during the cholera epidemic in Bergen in 1848-49]. AB - In Norway temporary regulations were issued for control of cholera. An important provision was that Municipal Boards of Health should be appointed. The author describes the duties of the Board of Health, and how it functioned during the cholera epidemic in Bergen in 1848-49. The cholera broke out on 10 December 1848, and a Board of Health was appointed exactly one week later. The Board held frequent meetings and the minutes provide good information on the development of the epidemic and the activities of the Board. The fact that the Chief Medical Officer was not a member of the Board was in violation of the regulations. However, he usually attended the meetings and strongly influenced the decisions. It may have been considered an advantage that the Chief Medical Officer acted relatively freely, even if the overall responsibility lay with the Board. This led, however, to some doubt about responsibility, and concerning what were the official channels. PMID- 8493676 TI - [Michael Sars and cholera in Manger 1849]. AB - In December 1848, cholera struck the city of Bergen, Norway. During the following months the distant parish of Manger was also affected. The local doctor was among the first victims, and although he survived, he was unable to take part in the fight against the epidemic. Instead, the local priest, Michael Sars (1805-69), took command of the situation. He organized new graveyards, materials for coffins, medicines, a cholera doctor from Bergen, and a local cholera hospital. Some of the peasants who were unwilling to comply with the regulations for burial of cholera victims were reported to the police. Michael Sars left the priesthood in 1854, and was appointed professor of zoology. He became one of Norway's most famous marine biologists. PMID- 8493677 TI - [Grief and crises in Norse literature]. AB - The significance of literature for psychiatry and vice versa is commented on, as an introduction to a study of Norse literature. This was written down mainly in Iceland in the 13th Century on the basis of oral traditions, some of which date back to the 9th century. From a psychological point of view, the Icelandic Sagas, the Royal Sagas of Snorri Sturluson and the earliest hero-poems of the Edda are of particular interest. This literature includes detailed descriptions of grief and crisis reactions, the management and rituals of grief, and the associated rituals. These patterns have a striking similarity to modern principles of crisis intervention. PMID- 8493678 TI - [Ibsen and sunshine]. AB - It is known that some people become depressed in winter, and that treatment with light can be effective in such cases. A reasonable explanation of this depression seems to be lack of sunshine. The connection may be that light possibly influences the secretion of certain amines in the brain. The author believes that Henrik Ibsen was among those who are more dependent than others on sunshine for optimal function. This may explain why his moving from often dark, cold and rainy Norway to warm, sunny Italy in 1864 meant so much to him. It was a dramatic event in his life and he used it in his writing, especially in the three plays: Emporer and Galilean, Ghosts and When We Dead Awaken. In each of these three plays, happiness in sunshine is used as a contrast to the sadder, dark and unhappy aspect of life. Ibsen, the earnest man and author was a sunshine poet. He really loved the sun, perhaps because he himself was among those who, without sun, become depressed and downhearted and loose their love of work. PMID- 8493679 TI - [Physicians as crime writers and literary detectives]. AB - Doctors have played an important role in the development of the crime story--both internationally and in Norway. This paper reviews the biographies of some well known writers and their sleuths--from Sir Arthur Conan Doyle to contemporary Norwegian authors. PMID- 8493680 TI - [Avalanche accidents]. AB - Most avalanche victims die from asphyxia (68%) followed by trauma (13%). Hypothermia is a less common cause of death. Asphyxia may be caused by obstructed airways owing to aspiration of snow, an immobile thorax due to compression by the surrounding snow or lack of diffusion of oxygen through the mass of snow. Clearing airways and quick mobilization of the thorax are of utmost importance in the initial treatment. Cardiopulmonary resuscitation may be required. Unconscious victims without vital signs should be treated in the same way as victims with severe hypothermia. PMID- 8493681 TI - [Cancer patients who want to die at home]. AB - During the years from 1989-92, 18 patients, at their own wish and the wishes of their family were transferred from the Department of Oncology at the University Hospital of Tromso, to their homes for terminal care. There were nine women and nine men, all from the city of Tromso. Their age varied from 28-82 years. The most frequent disease was colorectal carcinoma, and the most frequent occupations were housewife and office worker. Women and patients with adult children remained at home for a longer period of time than the others. Six patients lived at home for more than one month. The care was most often provided by the spouse. PMID- 8493682 TI - [When a cancer patient dies at home--experience of the relatives]. AB - Between 1989-92, 19 patients were transferred from the Department of Oncology to their homes for terminal care. Their care providers were questioned retrospectively. 16 responded. They all recommended other families with cancer patients to care for these patients at home. 14 reported feelings of inadequacy, anxiety, burn-out, insecurity or loneliness. Their most important contacts were nurses from the municipal home care service and the oncologists. Small children were not reported to limit the possibility of care at home. Family and friends were the best source of support during the period following the bereavement. PMID- 8493683 TI - [Anxiety in general practice]. PMID- 8493684 TI - [Cancer anxiety in Somna--created by Dagsrevyen?]. PMID- 8493685 TI - [The HELLP syndrome]. PMID- 8493686 TI - [I accuse! Whiplash injuries]. PMID- 8493687 TI - [Behavior is formed and selected by its consequences]. PMID- 8493688 TI - [Empathy. On physician's role and empathy]. PMID- 8493689 TI - [Kipling's poem "If" and our secret debate on bone marrow transplantation]. PMID- 8493690 TI - [Health problems of immigrants and refugees--only of soul?]. PMID- 8493691 TI - [Science about the unscientific]. PMID- 8493692 TI - [An American health care reform is unavoidable]. PMID- 8493693 TI - [Air pollution in a global perspective]. PMID- 8493694 TI - [Help to self help--past and present]. PMID- 8493695 TI - [A little about coffee drinking]. PMID- 8493696 TI - [The treatment of recurrence in children with acute lymphatic leukemia. Current results and various developments]. AB - The results of current treatment of relapsed childhood acute lymphoblastic leukemia (ALL) are discussed, together with some recent developments which (might) influence such treatment. At present more than 95% of children with ALL will achieve a complete remission (CR), and +/- 70% will remain in CR. Nevertheless, 20-30% of the patients suffer a relapse, which implies a less favorable prognosis. However, after intensive treatment a part of these patients will have a prolonged second complete remission: 30-50% of children with a late relapse and 0-20% of children with an early relapse. It is important to prevent the occurrence of a relapse. The identification at diagnosis of patients at high risk for a relapse, and a subsequent more specific and more intensive treatment of these patients might contribute to that goal. Well-known risk factors are briefly mentioned, factors of which the prognostic significances is therapy dependent. In addition, the treatment of relapsed ALL needs further improvement. Some alternatives to achieve this goal are discussed, including the role of in vitro cytostatic drug resistance testing. PMID- 8493697 TI - [Application of non-glycoside inotropic agents in newborn infants]. AB - Non glycoside inotropic agents are regularly used in the treatment of critically ill neonates. There are reasons to believe that the neonate reacts differently to these inotropic agents because of differences in physiology and maturation. In this paper the oxygen consumption and oxygen transport, heart failure in the newborn, effects of non glycoside inotropic agents in general and the doses of the commonly used inotropic agents (dopamine, dobutamine and isoproterenol) will be discussed. Finally a review of the literature and a therapeutic advise on the use of inotropic agents in the neonate is presented. PMID- 8493698 TI - [Ureaplasma urealyticum in tracheal aspirate of ventilated premature infants: report of 6 cases]. AB - In the Netherlands, up till now no reports have appeared describing neonatal colonisation of mechanically ventilated preterm neonates with Ureaplasma urealyticum. The present, prospective study was designed to assess the incidence of U. ureaplasma infections in a group of preterm newborns with prolonged ventilatory support because of respiratory failure. In 1989 110 preterm newborns with hyaline membrane disease (HMD) were mechanically ventilated; 23 for more than 7 days because of pulmonary abnormalities. Six of them (26%) had positive cultures of endotracheal aspirate for U. urealyticum. Gestational age at birth ranged from 26 to 33 5/7 weeks, birth weight from 790 to 2545 gram. Other bacteria or viruses were not present. Although all patients with positive cultures for U. urealyticum were treated with erythromycin and U. urealyticum was eradicated, no clinical effect was seen. Five of the 6 patients (83%) with U. urealyticum developed bronchopulmonary dysplasia (BPD), 2 of them (33%) died. Of the 17 neonates without U. urealyticum 9 (53%) developed BPD, whereas one (6%) died. Differences were not significant (Chi 2 test/Fisher exact test). Also in the Netherlands U. urealyticum can be demonstrated in endotracheal aspirate of ventilated preterm newborns. The hypothesis, that early diagnosis and treatment of U. urealyticum in this group of patients might decrease the morbidity and mortality caused by HMD and BPD, needs further study. PMID- 8493699 TI - [Main points and concerns in plagiocephaly]. AB - An asymmetrical head (plagiocephaly) may be due to premature closure of the sutures of the skull (craniosynostosis) or to prolonged pressure on one side of the head in the pre- peri- or postnatal period. The latter deformity may be part of the squint baby syndrome. The diagnosis is based on a careful history and physical examination. X-rays of the skull and/or the cervical vertebral column are seldom necessary to confirm the diagnosis. Physiotherapy in an early stage, directed toward plagiocephaly and associated disorders, results in a complete disappearance of symptoms in a high percentage of cases. PMID- 8493700 TI - [The Coffin-Siris syndrome. Description of 4 patients and a literature review]. AB - Four patients with Coffin-Siris syndrome are described. In addition a 30 cases are reviewed. The most frequent symptoms are dysmorphic features of the facies with sparse scalp hair, nail hypoplasia and mental retardation. PMID- 8493701 TI - [Complete situs inversus in one half of monozygotic twins]. PMID- 8493702 TI - [The clinical significance of anti-gliadin antibodies determination in blood of children with suspected celiac diseases]. AB - Screening tests for coeliac disease may be useful to select the patients who should undergo a small intestine biopsy. It has been reported that the determination of serum levels of anti-gliadin antibodies is a good screening method for small intestine damage in coeliac disease. We have retrospectively assessed the value of the anti-gliadin antibody test in detecting villous atrophy of the small bowel. Antigliadin antibodies were measured with an ELISA technique in sera of 44 children seen at the Department of Paediatrics, Leiden University Hospital, who underwent 53 small intestine biopsies because of suspected coeliac disease. The relation between the histopathological findings of the small intestine and the results of the anti-gliadin antibody quantifications in serum were studied. In 9 of the 10 children with villous atrophy high Ig total and IgG titers were found. Five children with villous atrophy, 2 of them with a selective IgA-deficiency, had normal IgA-AGA titers in serum. 17 Children with normal biopsies had high Ig total and IgG-AGA titers, but no child with normal small intestine biopsy had high IgA-AGA titers in serum. We conclude that the determination of anti-gliadin antibodies as screening for mucosal damage must be based on the measurement of antibodies within the IgG as well as the IgA class. PMID- 8493703 TI - Potential bile acid metabolites. 19. The epimeric 3 alpha,6,7 beta-trihydroxy- and 3 alpha,6,7 beta,12 alpha-tetrahydroxy-5 alpha-cholanoic acids. AB - Syntheses by a new procedure of the known 3 alpha,6 alpha,7 beta- and 3 alpha,6 beta,7 beta-trihydroxy-5 alpha-cholanoic acids, and of the once-reported analog 3 alpha,6 alpha,7 beta,12 alpha-, as well as the new 3 alpha,6 beta,7 beta,12 alpha tetrahydroxy-5 alpha-cholanoic acids, are described. Key intermediates of the syntheses are the 6-oxo-7 beta-ols of the respective 5 alpha-cholanoic acids (and their methyl esters) prepared by allomerization at C-5 of appropriate 6-bromo-7 oxo derivatives of the corresponding 5 beta-acids. Successful reduction of the 6,7-ketols to the desired products depended on the proper choice of reagents, either Zn(BH4)2 or Li/NH3/MeOH. PMID- 8493704 TI - Inhibition by glycyrrhetinic acid of rat tissue 11 beta-hydroxysteroid dehydrogenase in vivo. AB - Inhibition of 11 beta-hydroxysteroid dehydrogenase (11-HSD) in the major organs of the rat by the inhibitor glycyrrhetinic acid (a component of licorice) was investigated. The inhibitor decreased 11-HSD levels in most organs after intraperitoneal injection. The effect was dose dependent, was maximally effective 3 hours after administration, and was completely reversed at 24 hours. The magnitude and patterns of effectiveness differed between tissues. It was concluded that the inhibition of 11-HSD by glycyrrhetinic acid is not restricted to one or a few organs, but is broadly based. PMID- 8493705 TI - A synthesis of 7 alpha-substituted estradiols: synthesis and biological evaluation of a 7 alpha-pentyl-substituted BODIPY fluorescent conjugate and a fluorine-18-labeled 7 alpha-pentylestradiol analog. AB - In an effort to assist in the preparation of ligands for the study of the estrogen receptor (ER), we have developed a new synthesis of 7 alpha-substituted estradiols. The key step in the synthesis involves a copper-catalyzed, alpha selective, 1,6-conjugate addition of 4-pentenyl magnesium bromide to a suitably protected 6-dehydrotestosterone derivative. Desaturation and then reductive aromatization of the resulting 7 alpha-pentenyl androgen gave the 7 alpha pentenylestradiol in good yields. The alpha-stereoselectivity of this addition in the testosterone series, compared with the 19-nortestosterone series, is significantly improved by the presence of the C-19 methyl group, which shields the beta face from attack. A key intermediate was functionalized further by substitution with fluorine-18 to provide a potential imaging agent for positron emission tomography, and by conjugation with a BODIPY (Molecular Probes Inc., Eugene, OR, USA) fluorophore to make a fluorescent probe for the estrogen receptor. The synthesis and biological evaluation of these analogs is presented, as well as a discussion of the improvements in the synthetic procedure. PMID- 8493706 TI - Conformational analysis of A and B rings in 2-, 4-, and 6-bromosubstituted steroidal 4-en-3-ones by nuclear magnetic resonance. AB - The conformational preference of A and B rings in four differently functionalized bromosubstituted 4-en-3-one steroids is studied by concerted application of high resolution one- and two-dimensional nuclear magnetic resonance (NMR) techniques, such as homonuclear and heteronuclear correlated spectroscopy, transient and steady-state nOe spectroscopy, temperature-dependent chemical chemical shift variation, and application of a modified Karplus equation. The steroids studied include 6 beta-bromocholest-4-en-3-one (3), 4,6 beta-dibromocholest-1,4-dien-3 one (2), 2 alpha,4,6 beta-tribromocholest-4-en-3-one (1), and (25R)-2 alpha,6 beta-dibromospirost-4-en-3-one (4). Steroids 1-4 were prepared by either acid catalyzed or free-radical bromination from appropriate 4-en-3-one steroid. The study has yielded an insight into the factors responsible for conformational preferences of the A and B rings of these bromosubstituted steroids. Bromosubstitution at the 2 alpha position is responsible for the inversion of the A ring to inverted 1 beta,2 alpha-halfchair conformation. The electronic interaction between 4-bromine and carbonyl oxygen distorts the A-ring conformation further. Inversion of the A ring has a concomitant effect of distortion in the chair form of the B ring. Conformational preferences of A and B rings are not found to be influenced by transmission effect of a side chain or oxygenated ring system. Temperature-dependent NMR studies indicate the reduced conformational flexibility of the A ring for 2 alpha-bromosubstituted steroids. Complete assignment of the 13C and 1H resonances of two of the steroids studied (3 and 4) is presented. PMID- 8493707 TI - Distribution of cholesterol in Caribbean marine algae. AB - Eleven species of Caribbean marine algae (red, green, and brown) were investigated for their cholesterol content. All of them were found to contain this sterol. Consistent with previously reported results, all five red algae contained large quantities of cholesterol. However, the two brown algae and three of the four green algae in our study also contained significant quantities of cholesterol. PMID- 8493708 TI - Synthesis of 17a-alkyl- and 17a-aryl-3 beta-acetoxy- and 3 beta-methoxy-17a-aza-D homoandrost-5-en-17-one. PMID- 8493709 TI - Steroids 48. Synthesis of 16 alpha-ethyl-21-hydroxy-19-norpregn-4-ene-3, 20-dione from 17-substituted 3-methoxyestradiols. PMID- 8493710 TI - Simultaneous transplantation. AB - 1. Thoracic organ transplantation requires extensive preparation with little advance notice. 2. A single organ transplant requires a team of various staff members, and may include one or two circulating nurses, two scrub technologists or nurses, one perfusionist, one surgeon's assistant, two surgeons, and one anesthesiologist. 3. Timing is important in organ transplantation because thoracic organs ideally should be transplanted within four hours after cross clamping the aorta of the donor. 4. The dedication, expertise, and thorough follow-up care provided by transplant surgeons, nurse transplant coordinators, organ procurement coordinators, and the CICU and coronary care nurses/departments directly relate to the success of a thoracic organ transplant program. PMID- 8493711 TI - New Jersey does it again: using unemployment funds for indigent health care. PMID- 8493712 TI - When the OR nurse is discouraged. AB - 1. Though not often associated with OR staff, discouragement (defined as a lack of confidence) is occasionally experienced by OR nurses. 2. Factors that contribute to feelings of discouragement include environmental stressors, personality characteristics, and physical and emotional status. 3. Methods to decrease feelings of discouragement include identifying sources of discouragement, communicating concerns through appropriate channels, sharing feelings with trusted others, increasing knowledge in areas of ignorance, and focusing on positive aspects of the job. PMID- 8493713 TI - Sterilization practices: past, present, and future. AB - Processing of instruments has become complex. OR nurses are sometimes assigned this responsibility without having proper knowledge and understanding of processing procedures. Formal continuing education programs and continuous quality reviews must be carried out to ensure appropriate processing of OR equipment. PMID- 8493714 TI - Cluster staffing: cooperation, competence, and caring. AB - 1. A very large OR staff that deals with a multitude of specialty areas may find it difficult to keep up skill and knowledge levels in all areas. This may lead to staff dissatisfaction and a high turnover rate. 2. Partially by allowing staff to chose their own clusters, cluster staffing works to increase staff satisfaction, to increase the clinical knowledge "comfort zone," to improve efficiency, and to reduce the turnover rate. 3. The results of cluster staffing at the University of Massachusetts Medical Center indicate that staff are happier, are more relaxed, focus more on patient care, and work together more efficiently. PMID- 8493715 TI - HIV health care costs surpass previous estimates. PMID- 8493717 TI - Stop smoking in 28 days. PMID- 8493716 TI - A new graduate nurse chooses the OR. PMID- 8493718 TI - Percutaneous laser diskectomy. An alternative method. AB - 1. The percutaneous posterior approach with laser to a herniated lumbar intervertebral disc--heralded as a "minimal invasion" treatment for the symptomatic relief of discogenic back pain and sciatica--is an alternative method for the treatment of protrusion of a lumbar disc and its associated radiculopathy. 2. Percutaneous diskectomy is considered in patients who have unremitting radiculopathy with a contained disc herniation. The particular criteria for patient selection includes: evaluation of the patient's pain, performance status, medication dependence, and duration of symptoms. The patient must have demonstrable neurological impairment, positive nerve root tension signs, and correlative findings on imaging studies. 3. Percutaneous laser diskectomy has multiple advantages: it is an outpatient procedure performed under local anesthetic; it is less traumatic than open diskectomy; there is no epidural fibrosis; and there is a quick functional recovery with minimal pain and few complications. PMID- 8493719 TI - The naming of parts. PMID- 8493720 TI - Positive patches and negative noodles: linking RNA processing to transcription? AB - A speculative model is presented that proposes specific mechanisms for effecting co-transcriptional splice site selection in pre-mRNAs. The model envisions that certain splicing factors containing arginine-rich, positively charged regions bind via these positive patches to the hyperphosphorylated, negatively charged tail of elongating RNA polymerase II. Thus tethered to the transcription machinery, these splicing factors gain access to signals in nascent transcripts as they emerge from the polymerase. PMID- 8493721 TI - Progress in protein structure prediction? AB - Prediction of protein secondary structure is an old problem and progress has been slow. Recently, spectacular success has been claimed in the blind prediction of the catalytic subunit of the cAMP-dependent protein kinase. When predictions in this and other test cases are assessed critically, some claims of prediction success turn out to be exaggerated, but a kernel of real progress remains: protein structure prediction can be improved substantially when a family of related sequences is available. Enough so that molecular biologists equipped with a new amino acid sequence and a multiple sequence alignment in hand may be tempted to test the new prediction methods. PMID- 8493722 TI - Epimorphin is related to a new class of neuronal and yeast vesicle targeting proteins. PMID- 8493723 TI - Sequence similarities between cell regulation factors, heat shock proteins and RNA helicases. PMID- 8493724 TI - The nucleolar snRNAs: catching up with the spliceosomal snRNAs. AB - Despite their early discovery, research into the small RNAs associated with the eukaryotic nucleolus (snoRNAs) has lagged behind that of their cousins, the small nuclear RNAs which are known to function in mRNA splicing (spliceosomal snRNAs). Recent progress has now shown that the snoRNAs also occupy a vital niche in the RNA world, participating in the processing of ribosomal RNA. Like the spliceosomal snRNAs, the snoRNAs exist as ribonucleoprotein (RNP) particles which appear to assemble into a large multi-RNA RNP complex for pre-rRNA maturation. PMID- 8493725 TI - Molecular evolution of bacterial cell-surface proteins. AB - The cell-surface proteins of the infective bacteria Streptococcus and Staphylococcus are probably involved in the process of infection. These proteins share many features including secretion signal peptides, cell-wall spanning regions, membrane anchor domains and repeated domains of various functions. These common features may have evolved by gene duplication and swapping of gene fragments. PMID- 8493726 TI - Autoimmune disease and molecular mimicry: an hypothesis. AB - Helper T lymphocytes are normally only stimulated to initiate an immune reaction through the recognition of peptides bound to class II major histocompatibility complex (MHC) molecules. Class II MHC molecules are constitutively expressed on antigen-presenting cells which play a critical role in the initiation of immune responses. In disease states, however, other cells often express class II MHC molecules inappropriately. This article suggests an hypothesis for the pathogenesis of autoimmune diseases based on molecular mimicry. The mimicry described is between microbial or viral peptides presented by antigen-presenting cells and self peptides presented inappropriately on a target tissue. This leads to helper T cells, stimulated by peptides derived from infectious organisms, initiating an autoimmune attack on the target tissue. PMID- 8493727 TI - Is anyone out there listening? PMID- 8493728 TI - [Destabilization of the discus articularis with rupture of the ulnar styloid apex in distal radius fracture. Diagnosis with dynamic MR]. AB - An avulsion of the ulnar styloid apex led--because of a simultaneous rupture of the ulnar collateral ligament and a rupture of the disc's insertion in the fovea ulnaris--to a displacement of the triangular fibrocartilage. During movements in the frontal plane, the latter underwent a deformation, was displaced, compressed and blocked ulnar abduction. This pathology and the ulnar impingement could be observed in a "MRI-movie". PMID- 8493729 TI - [Double stomach rupture as isolated injury]. AB - A 19-year old female patient was admitted after a motorbike accident. The only injury was a double gastric rupture, which was probably caused by gastric dilatation owing to an over-consumption of carbonic acid fluids immediately prior to the accident. PMID- 8493730 TI - [Conservative treatment of subcapital humerus fractures. A comparative study of the classical Desault bandage and the new Gilchrist bandage]. AB - In a randomized prospective comparative study, we treated 28 patients with a fresh fracture of the proximal humerus alternating with a classical Desault bandage or with the new Gilchrist-bandage. The two different bandages had no influence on the fracture healing or the functional end results. The Gilchrist bandage was clearly superior to the Desault-bandage in a subjective and objective appreciation: the patients had less complaints in applying the bandage, had less skin irritations and felt less pain during the whole immobilisation period. PMID- 8493731 TI - [Specialist quality versus formal specialist qualifications. Comments on the decision of the BGH 10 March 1992 VI ZR 64/91]. PMID- 8493732 TI - [Changes in the femoral nerve and medial articular nerve after medial arthrotomy and replacement of the anterior cruciate ligament]. AB - The effect of combined medial arthrotomy (Payr's approach) and replacement of the anterior cruciate ligament upon the femoral nerve and the medial articular nerve has been studied. Resection and prosthetic replacement of the anterior cruciate ligament was performed on the right hindlimb of twelve Merino sheep. Three unoperated animals served as controls. Eight to 48 weeks after the operation, myelinated axons of the femoral nerve and the medial articular nerve were examined using morphological and morphometric methods. Compared with the un operated control side, only discrete morphological alterations were detectable, such as an increase in non-circular axons. In contrast, considerable morphometric changes were observed: A decrease in large axons and an increase in small axons were found in the femoral nerve of the operated side resulting in a significant reduction in axon diameter (p < or = 0.05). This decrease in axon diameter was associated with a significant increase in the number of axons. Both changes persisted throughout the period examined (48 weeks). Similar changes, i.e. increase in small axons, decrease in large axons and reduction in mean axon diameter were also observed in the medial articular nerve. The results show that medial arthrotomy with prosthetic replacement of the anterior cruciate ligament results in irreversible changes of the femoral nerve and the medial articular nerve. These findings indicate that the medial articular nerve is injured during medial arthrotomy. Mechanisms are discussed which may explain the alterations observed in the femoral nerve a long distance (30 to 35 cm) away from the operation site. PMID- 8493733 TI - [Experimental evaluation of various anchoring techniques for synthetic ligaments]. AB - One of the weak points of augmentation or replacement of cruciate ligaments by synthetic material is the fixation of these artificial ligaments to the bone. The present investigation examines the mechanical properties of a newly developed anchoring technique (ligament fixation device = LFD) in regard to linear and maximum load, stiffness, creep, and long-term durability compared to single staples, double staples in belt buckle technique, and passing the ligament through an additional bone tunnel. The tests are carried out on cadaver knees and plastic bones under standardized conditions with the same artificial ligament in all experiments (Trevira hochfest). The LFD shows a linear load of 1866 N in cadaver knees and 1874 N in plastic bones. The stiffness is 68.3 N/mm respectively 51.9 N/mm, the elongation at 500 N load 12.7 mm respectively 10.9 mm. In the hysteresis tests with submaximum loads the ligament/LFD-unit lasts 8515 cycles in the plastic bone and 4431 cycles in the cadaver knee. These results are significantly superior to all other fixation techniques concerning linear load, stiffness and long-term durability. They permit aggressive functional treatment and immediate postoperative weight bearing of the operated knee. PMID- 8493734 TI - [Polytrauma and predicting fatality. Comparative evaluation of the value of the Kirkpatrick-Youmans Trauma Index (TI), Schreinlechner-Eber modified TI (TI mod.), and the Baker Injury Severity Score]. AB - The Trauma Index (TI) of Kirkpatrick and Youmans modified by Schreinlechner and Eber performed better than the Injury Severity Score (ISS) in predicting case fatality of 234 patients with major trauma treated during the years 1985 through 1987. Logistic regression was used for determining the cut-points: Death was considered as predicted by ISS if it was greater than 53 or by TI if it was greater then 3.74. Specificity was 95% for ISS and 94% for TI. Sensitivity was 49% for ISS and 73% for TI. PMID- 8493735 TI - [Complications of plate osteosynthesis of femoral fractures]. AB - Although the introduction of the locking pin in the management of upper thigh fractures has widened the range of possible indications for intramedullary fixation, there are still cases where the DCP technique is applied. When using DCP, it is essential that the graft chosen has the appropriate length and that great attention is given to correct technique, because plating is still associated with a higher complication rate than intramedullary fixation. PMID- 8493736 TI - [Isolated fracture of Volkmann's triangle--a unique injury]. AB - 25 rare isolated fractures of the dorsal tibial margin out of 2500 ankle-lesions have been analysed. The mechanism consists of extensive plantar flexion followed by axial impact of the astragalus against the posterolateral part of the mortise. The tense condition of the syndesmotic apparatus forces it to pull off the dorsal insertion wedge on the distal tibia with an articular component of different size. Small and undislocated fragments are prevalent. Torn anterior tibiofibular ligament and parts of the interosseous membrane are typical concomitants of this lesion. Neither fibular nor medial structures of the ankle joint have been harmed. Orthotopic bony union of the tibial margin and ligament healing is safe within three weeks of non-weight-bearing immobilisation followed by the same period of walking cast. Large dislocated fragments require operation. Most patients have excellent or good results as our follow-up study confirms. PMID- 8493737 TI - [Antineutrophil cytoplasmic antibodies in human pathologies]. AB - The prevalence of antineutrophil cytoplasmic antibodies (ANCAs) was verified in 338 patients with various rheumatic diseases using the internationally standardized indirect immunofluorescence method. The method was improved by using ethidium bromide as a nuclear counterstain. We observed three patterns of fluorescence: the classical diffuse cytoplasmic granular staining (C); the perinuclear one (P) and a yet undescribed atypical cytoplasmic distribution (A). We thus found ANCAs in 14/15 (93%) patients with active Wegener's granulomatosis: 13 were C-ANCAs, 1 was P-ANCA. We also found ANCAs in 6/25 (22%) patients with other systemis vasculitides (essentially those with small vessel vasculitis): they were C-ANCAs (3 cases) or P-ANCAs (3 cases). Finally, ANCAs were detected in 10/185 patients with various autoimmune diseases (5 with rheumatoid arthritis and 5 with systemic lupus erythematosus): they were C-ANCAs (1 case), P-ANCAs (4 cases) or A-ANCAs (5 cases). No ANCAs were found in 100 control patients with miscellaneous diseases. The isotype distribution of ANCAs is essentially limited to IgG classes and the serum titre usually reflects disease activity. The technical improvement facilitates the distinction of ANCAs from other antinuclear and anticytoplasmic autoantibodies found in connective tissue diseases. Our data emphasize the clinical importance of ANCA detection and justify our efforts to develop more specific and quantitative assays. PMID- 8493738 TI - [Update for 1991. 6. Acetylsalicylic acid and the primary prevention of cardiovascular diseases. Canadian study group on the periodic medical examination]. PMID- 8493739 TI - [Rheumatoid arthritis and arthrosis: we can do a lot but supporting research is indispensable]. PMID- 8493740 TI - [Cushing syndrome of hypophyseal or adrenal origin?]. PMID- 8493741 TI - [Financing of a health system: proof of creativity]. PMID- 8493742 TI - [Insomnia]. PMID- 8493743 TI - [Disseminated intravascular coagulation]. PMID- 8493744 TI - [Phlebothrombosis or thrombophlebitis? That is the question!]. AB - We have studied retrospectively 29 patients with a red blood cells venography preceded by a flow study allowing the evaluation of the microcirculation of the limbs. Fifteen of these patients had a normal flow study and fourteen had an increased one. We have correlated these 2 groups of patients with their incidence of pulmonary embolism. With the normal flow study, there was an incidence of 12/15 (80%) of pulmonary embolism and with the increased flow, it was 6/14 (43%). We conclude that the flow study preceding the red blood cells venography can identify a subgroup of patients at high risk of pulmonary embolism. PMID- 8493745 TI - [Musculoskeletal ultrasonography of the extremities: clinical applications]. AB - Sonography is a non-invasive and efficient imaging modality for the evaluation of musculoskeletal disorders of the extremities. This technique is still underutilized in the work of these types of lesions. Our goal is to review recent development of this modality and to identify its most common and useful clinical applications. PMID- 8493746 TI - Problems in the radiologic diagnosis of renal parenchymal tumors. AB - There has been a great increase in the detection and earlier diagnosis of a host of renal parenchymal tumors because of the continued improvement in imaging studies. Although this change will tend to improve the cure rate of renal cell carcinoma, it also has uncovered many cases that are problematic in both diagnosis and management. It is hoped that performance of high-quality examinations and the experience gained in dealing with these cases have improved our ability to diagnose and manage these problematic cases successfully. PMID- 8493747 TI - The radiologic evaluation of the patient with renal cancer. AB - Radiologic procedures are used for detection, differential diagnosis, staging, and follow-up in virtually every patient with renal cancer. This article reviews the best imaging techniques for each of these tasks, the capacities and limitations of each modality, the clinical situations that call for their use, and the proper timing and order of radiologic workup. PMID- 8493748 TI - Prognostic factors in renal cancer. AB - In conclusion, the accumulated data indicate that the local extent of a renal carcinoma at the time of surgical intervention is the most important single variable in determining survival. Nuclear grade and cell type of the tumor appear to be of additional prognostic value, especially in patients whose tumor has spread beyond the anatomic confines of the kidney, because these variables may reflect the biologic virulence of the particular tumor in the individual host. Nuclear morphometry and cellular DNA content may play a more important role in the future by identifying that population of patients with clinically localized disease in whom radical nephrectomy will not be not curative, presumably because of concurrent undetectable micrometastases. This distinction will become increasingly important as more effective adjuvant therapies are identified. PMID- 8493749 TI - Surgery of renal cell carcinoma. AB - The overwhelming determining factor in survival for renal cell carcinoma is the total surgical removal of the tumor. Preoperative assessment of tumor stage is critical in determining the surgical approach especially regarding the presence and extent of tumor thrombus. Interoperative techniques are discussed as well as parenchymal sparing procedures and the role of surgery in advanced disease. PMID- 8493750 TI - Renal-sparing surgery for renal cell carcinoma. AB - The role of nephron-sparing surgery for renal cell carcinoma is evolving, and continued careful evaluation of patient outcome data is needed to define appropriate limits for this approach. Both accepted and controversial aspects of this approach are reviewed in this article. PMID- 8493751 TI - Autolymphocyte therapy in the treatment of metastatic renal cell carcinoma. AB - Autolymphocyte therapy is outpatient adoptive immunotherapy based on the infusion of ex vivo activated memory T cells. Autolymphocyte therapy has been used to treat more than 500 patients with renal cell carcinoma and the mechanism of action as well as the clinical outcome of data are reviewed. PMID- 8493752 TI - Cytotoxic chemotherapy for advanced renal cell carcinoma. AB - This article reviews 72 cytotoxic chemotherapeutic agents used singly or in a limited number of two drug combinations. Results in 3502 adequately treated patients show objective response (complete and partial remissions) in only 197 or 5.6% (95% CI, 4.8% to 6.4%). Although some data suggest that a few drugs need further evaluation, at this time, renal cell carcinoma must be considered a chemotherapeutically resistant cancer. PMID- 8493753 TI - Treatment options for upper tract transitional-cell carcinoma. AB - Nephroureterectomy with a bladder cuff remains the gold standard of treatment of transitional-cell carcinoma of the upper urinary tract. The natural history of the disease, specifically its multifocal nature and its propensity for local recurrence, argues for an aggressive treatment approach. Good clinical results using renal-sparing treatment of low-grade ureteral tumors reveal the feasibility of renal-sparing approaches in limited circumstances. It is likely that, with increasing use of renal-sparing therapy by endoscopic means, topical chemotherapeutic agents will take on an analogous role in the treatment of superficial disease and their role on the treatment of bladder cancer. PMID- 8493754 TI - Renal oncocytoma. AB - Renal oncocytomas are believed to arise from the intercalated cells of the renal collecting tubules. Specific chromosomal abnormalities, which differentiate oncocytomas from renal cell carcinomas, have been found. Renal oncocytomas exist and behave differently from renal cell carcinomas. Urologic clinical judgement and surgical practice must evolve to keep pace with the knowledge that oncocytomas and renal cell carcinomas are different diseases. PMID- 8493755 TI - [AUO guidelines. Practical information for planning and execution of studies 1993. Association of Urologic Oncology]. PMID- 8493756 TI - Experimental infection with Toxoplasma gondii in farmed mink (Mustela vison S.). AB - Live Toxoplasma gondii tissue cysts (Strain 119) were administered orally to five mink (Mustela vison S.) and five mink were inoculated with a suspension of ultrasonicated Toxoplasma gondii trophozoites (RH-strain). Seroconversion was observed in all animals administered live T. gondii cysts indicating that infection was established. Likewise seroconversion was observed in three out of four animals administered ultrasonicated T. gondii trophozoites. Faecal shedding of oocysts of T. gondii was not demonstrated in any of the infected animals. Histologically chronic meningitis with calcification was seen in all animals. Cerebral T. gondii tissue cysts were detected in four animals administered live tissue cysts. The study demonstrates that mink can be experimentally infected with T. gondii, thus representing a potential infection source for man, when considering the pelting procedure. PMID- 8493757 TI - Effects of cattle tick (Boophilus microplus) infestation on the bovine immune system. AB - The immunosuppressive effect of experimental Boophilus microplus infestation on bovine peripheral blood lymphocytes (PBL) and on host antibody production to a protein antigen (ovalbumin) was examined. Boophilus microplus infestation caused a marginal decrease in the percentage of T lymphocytes in PBL, which was observed in both lightly (5000 larvae) and heavily (40,000 larvae) infested cattle, and began at the second infestation and continued until the end of the fourth infestation. The percentage of B lymphocytes in heavily tick-infested cattle was less than that in non-infested control cattle after the fourth infestation. The response of PBL from tick-infested cattle to phytohemagglutinin (PHA) was always less than that of tick-free cattle after the second infestation. No noteworthy differences were detected between the three stages of tick infestation, that is, 1 week before the peak of adult engorgement, the middle of the peak and 1 week after all ticks had dropped. Boophilus microplus saliva (100 microliters ml-1) suppressed 47% of the response of bovine PBL to PHA in vitro. This suppressive effect of saliva may contribute to the lower responsiveness of PBL from tick infested cattle. Antibody production by tick-infested cattle was examined during the third and fourth heavy tick infestation. Tick-infested cattle showed a diminished response against ovalbumin after the second immunization. The immunosuppressive effects of tick infestation may play an important role in tick survival or in the transmission of tick-borne diseases in the field. PMID- 8493758 TI - Occurrence and overlapping of pharyngeal bot flies Pharyngomyia picta and Cephenemyia auribarbis (Oestridae) in red deer of southern Spain. AB - From 1985 to 1990, 372 red deer (Cervus elaphus) from southern Spain were examined for larvae of pharyngeal bot flies Pharyngomyia picta and Cephenemyia auribarbis. The infestation was related to age, sex and intensity of infection. Fawns and adult deer (more than 5 years old) had a significantly (P < 0.05) higher prevalence and intensity of infection than younger deer. Conversely, no significant difference has been noted between sexes. Ninety percent of deer were found to be infested. A simultaneous occurrence of both species was found in 23% of cases, with noticeable differences between prevalence and intensity of infection (measured in number of bots per head for each species). Quantitative overlapping between P. picta and C. auribarbis seems relative and their biological cycles did not overlap completely. PMID- 8493759 TI - Cell-mediated and humoral immune responses in immunized and/or Dermatobia hominis infested rabbits. AB - The cell-mediated and humoral immune response of rabbits to antigens from larvae of Dermatobia hominis were analyzed by leucocyte migration inhibition factor assay (MIF), immunodiffusion (ID) and passive hemagglutination (PH) test in rabbits immunized with D. hominis extract, in rabbits immunized and infested with the parasite and rabbits infested with D. hominis. Twenty rabbits were divided into five groups: Group 1, rabbits immunized with a crude antigen extract, evaluated for 40 weeks at 4 week intervals; Group 2, rabbits immunized and infested with newly hatched larvae at 14 weeks post immunization (PI) and evaluated as Group 1; Group 3, rabbits immunized, evaluated for 28 weeks at 2 week intervals; Group 4, rabbits immunized and infested at 4 weeks PI and evaluated as Group 3; Group 5, rabbits infested and evaluated for 24 weeks at 2 week intervals. Different patterns of reactivity were observed in the infested and immunized animals: immunized rabbits developed antibodies and cellular immune responses earlier and at higher levels during immunization than the infested rabbits; the infestation at 14 weeks PI, when the cell-mediated and humoral immune response began to decrease, or at 4 weeks PI when these parameters were at higher levels, elicited an anamnestic response. After the spontaneous elimination of larvae by the host, from the 4th week PI onwards, high titers of antibodies and migration inhibition indices were maintained for a long period. These results suggest that the onset of cellular and humoral immune responses after immunization may be important as a biological control of myiasis and contribute to better understanding of the immune defense mechanism of the host against D. hominis. PMID- 8493760 TI - A comparison of field tick infestation on N'Dama, Zebu and N'Dama x Zebu crossbred cattle. AB - Tick burdens, estimated from cumulative tick counts, were determined on N'Dama, Zebu and F1 N'Dama x Zebu crossbred cattle. N'Dama showed significantly fewer ticks than the Zebu and F1 cattle (P < 0.001). A previous trypanosomosis infection did not affect tick burdens on the three genotypes. Amblyomma variegatum had a prevalence of 84.8% and Hyalomma spp. 15.2%, with the ratio similar on all cattle breeds. Trypanosomosis infection increased the serological prevalence of Anaplasma marginale in Zebu and F1 cattle but not in N'Dama cattle. These observations supported the view that N'Dama cattle are less susceptible to tick attachment than Zebu cattle. PMID- 8493761 TI - Human interferon alpha fails to inhibit the development of Babesia bigemina and Anaplasma marginale infections in cattle. AB - Studies were undertaken to determine whether human interferon alpha (HuIFN-alpha) administered orally could inhibit the development of clinical disease caused by the intraerythrocytic protozoan Babesia bigemina and the intraerythrocytic rickettsia Anaplasma marginale in cattle. HuIFN-alpha did not inhibit intraerythrocytic multiplication of either of the two parasites, suggesting that there is no role for HuIFN-alpha administered orally in the control of these pathogens. PMID- 8493762 TI - Seroprevalence of Toxoplasma gondii in domestic ruminants in Bangladesh. AB - Sera from 205 cattle, 17 sheep and 306 goats were tested for Toxoplasma gondii antibodies by using a commercial latex agglutination test. Titres considered diagnostically significant (> or = 1:64) were detected in 16.10% of cattle, 17.65% of sheep and 12.09% of goats. Results indicate that T. gondii infection in domestic ruminants in Bangladesh is widespread. PMID- 8493763 TI - Survey of echinococcosis in eastern Ethiopia. AB - A total of 171 adult cattle and nine stray dogs were examined for Echinococcus granulosus in eastern Ethiopia. Prevalences of 20.5% and 22% were recorded in cattle and dogs, respectively. Some of the factors involved in the transmission dynamics are discussed. PMID- 8493764 TI - Diagnosis of Cryptosporidium on a sheep farm with neonatal diarrhea by immunofluorescence assays. AB - An outbreak of diarrhea in neonatal lambs occurred on a sheep farm in northern Ohio. Diarrhea commenced as early as 1 week of age and lasted for about 3-4 days. Although 100% of the newborn lambs were affected, most had recovered by 3 weeks of age. Cryptosporidium infection appeared to be the cause of diarrhea. Fecal examination of nine diarrheic newborn lambs (5-10 days old), 23 older lambs (2-3 weeks old, six with diarrhea) and 23 clinically normal ewes by immunofluorescence assays revealed infection rates of 100%, 78.3% and 17.4%, respectively. Most newborn lambs had high oocyst counts. Ewes were considered to be an important source of infection for lambs. PMID- 8493765 TI - Serological diagnosis of Trypanosoma evansi (Steel, 1885) in horses using a direct agglutination test. AB - A direct agglutination test is described to diagnose 'Mal de Caderas' caused by Trypanosoma evansi. The antigen used was a suspension of trypsin-treated parasites stabilized with formalin. The test was evaluated in horses with both natural and experimental infections. Test sensitivity and specificity were 94 and 97%, respectively. Treatment of serum with 2-mercaptoethanol before testing permitted the differentiation of IgM and IgG antibodies, and possible differentiation of current infection from past exposure to the parasite. The antigen was stable over a 6-month evaluation period and also showed good reproducibility between different batches. The direct agglutination test is proposed as another tool for diagnosis of T. evansi in horses, both for detecting clinical cases and for seroepidemiological studies. PMID- 8493766 TI - Vaccination of bovines against Schistosomiasis japonica with cryopreserved irradiated and freeze-thaw schistosomula. AB - Four laboratory tests and one field trial with cryopreserved irradiated (CI) schistosomula vaccine and a freeze-thaw (F/T) vaccine against bovine Schistosomiasis japonica were carried out in 1979 and 1980 with the following results: (1) Single intradermal vaccination in buffalo calves each with 10,000 20 krad CI Schistosomula plus 1 ml BCG gave 62% worm reduction (P < 0.05). Using the same protocol 55% worm reduction (P < 0.01) was obtained in cattle. (2) Buffalo calves immunized twice, at a 1.5 month interval, with 10,000 and 20,000 CI schistosomula, respectively, resulted in a worm reduction 65%. (3) In a preliminary field trial with 10,000 CI schistosomula plus 1 ml BCG resulted in a worm reduction of 53% in buffalo calves. (4) Intradermal vaccination of 30,000 F/T schistosomula with 1 ml BCG was also tried in cattle and revealed a worm reduction of 57% but increasing the number of vaccinations did not improve the protective effect. (5) Evidence regarding the effects of immunization with CI vaccine in buffaloes and F/T vaccine in cattle, on the number of eggs and miracidia and that of female worms themselves was obtained. (6) Immune responses, cellular and humoral, elicited in buffaloes vaccinated with CI schistosomula were detected by means of Lymphocyte Transformation Assay and Enzyme Linked Immunosorbent Assay. PMID- 8493767 TI - Fasciolosis in cattle in Louisiana. II. Development of a system to use soil maps in a geographic information system to estimate disease risk on Louisiana coastal marsh rangeland. AB - A geographic information system (GIS) model of habitat for Lymnaea bulimoides, the snail intermediate host of Fasciola hepatica and the rumen fluke, Calicophoron microbothrioides, on the Chenier Plain of southwest Louisiana was revised to incorporate broad (greater than 100 m) chenier (relict beaches) along with adjacent marsh and transitional soils associated with spatial distribution of L. bulimoides habitat. The proportion of farmland comprised of soils of the GIS model coincided with actual habitat from a previous survey with a sensitivity of 91.3% and a specificity of 80.1%, and regressed significantly against the proportion of farmland comprised of L. bulimoides habitat (n = 12, P = 0.01, r2 = 0.50, slope = 0.015). A soil model index was calculated to incorporate (1) the proportion of farmland comprised of soils of the GIS model and (2) stocking rate. Fluke egg shedding indices (mean egg count multiplied by prevalence) were calculated for each fluke species on nine farms at four sampling times over a 2 year period. The maximum egg shedding indices for each farm, taken to indicate potential fluke transmission intensity, were correlated for the two fluke species on herds not recently treated for fasciolosis (n = 9, P = 0.004, r2 = 0.72, slope = 0.2), although at no one sampling period were shedding indices of the two fluke species significantly correlated. Egg shedding of C. microbothrioides by cattle correlated with the proportion of farmland comprised of soils included in the GIS model (n = 9, Spearman's rank coefficient was 0.7, P = 0.05). We conclude that (1) the maximum of several observations of the C. microbothrioides egg shedding index may be useful as a surrogate for F. hepatica in estimating risk from snail habitat on a farm when regular flukicide treatment interferes with F. hepatica egg shedding, and (2) the GIS model may estimate site-specific differences in fasciolosis risk to cattle operations in the Chenier Plain based on the association of certain soils with snail intermediate-host habitat. PMID- 8493768 TI - Sudden death of calves by experimental infection with Strongyloides papillosus. III. Hematological, biochemical and histological examinations. AB - Nine calves infected percutaneously with graded doses of Strongyloides papillosus (SPL) were examined for hematological, biochemical and histological changes during the infection. Six of the calves infected with the highest larval doses died suddenly and the three calves given lower doses survived. No changes were observed in blood cell counts except for a transient eosinophilia. Parameters of the blood coagulation system and blood gas remained normal. A decrease in blood glucose was observed in four of the calves that died after the prepatent period of the parasite. However, endotoxic shock could be ruled out as a cause of death because of normal platelet counts, no intravascular coagulation and low levels of serum endotoxin. A transient increase of creatine kinase was observed in three of the calves that died; however, myocardial infarction or myocarditis were not observed. No lesions were observed except for minor inflammatory changes in the lungs and slight cellular infiltrations in the heart. In the absence of any consistent hematological, biochemical or histological changes in the calves that died, the present study failed to demonstrate mechanisms underlying sudden death due to SPL infection. PMID- 8493769 TI - A key to the identification of arrested gastrointestinal nematode larvae of sheep in Britain. AB - A simple key is presented for the identification of arrested larval nematodes recovered from the gastrointestinal tract of sheep slaughtered in Britain. The parasites included in this key are those species which are most commonly seen to undergo arrested development in sheep. They include Teladorsagia (Ostertagia) spp., Haemonchus contortus, Trichostrongylus axei, intestinal Trichostrongylus spp., Nematodirus battus, Nematodirus filicollis, and Cooperia spp. Easily identifiable morphological features, together with overall dimensions, are used to separate these species. PMID- 8493770 TI - Pattern of abomasal helminths in fallow deer farming in Umbria (central Italy). AB - Five helminth species were seen in the abomasa of 29 farmed fallow deer. Spiculopteragia asymmetrica was most common in both prevalence (96.6%) and abundance (166.2). Ostertagia drozdzi, Ostertagia arctica and Spiculopteragia quadrispiculata were also recovered with high prevalence (79.3-93.1%); Trichostrongylus axei was sporadic (3.4%). Yearlings had worm counts of 496-1480, adult males of 168-1720 and females of 18-2008. For nine of 13 deer, the faecal egg counts were negative and post-mortem examinations were positive, with 18-1140 worms per deer. The results are discussed in relation to helminth population, its epidemiological significance and management strategies. PMID- 8493771 TI - Inverse relationship between IgE and worm burdens in cattle infected with Ostertagia ostertagi. AB - Changes in serum total and Ostertagia-specific IgE levels, and pepsinogen concentrations were evaluated in 28 Holstein calves naturally or experimentally infected with Ostertagia ostertagi. In addition, IgE and pepsinogen concentrations were determined in abomasal lymph. Results showed that (1) lymph IgE responses were inversely correlated with worm burdens, and (2) serum IgE levels were unreliable for predicting worm burdens. PMID- 8493772 TI - Detection of oocysts and IgG antibodies to Cryptosporidium parvum in asymptomatic adult cattle. AB - Infection by Cryptosporidium was detected in 94 (71.75%) asymptomatic adult cattle from 131 fecal samples examined microscopically. In two cases Cryptosporidium oocysts were observed which were distinctly larger (5.5-6.5 microns x 6.6-7.0 microns) than those we had seen in the majority of feces examined (4.0-4.5 microns x 4.0-4.5 microns) and these specimens were considered to be Cryptosporidium muris; it is possible that the other oocysts should be considered as Cryptosporidium parvum. The seroprevalence of IgG antibodies to Cryptosporidium was 63.35% as detected by indirect fluorescent antibody test (IFAT) and 51.41% by enzyme-linked immunosorbent assay (ELISA). In 27 cases, the presence of IgG antibodies to Cryptosporidium (as tested by IFAT and ELISA) in serum samples was correlated with oocyst excretion. PMID- 8493773 TI - Evaluation of ivermectin at an elevated dose against encysted equine cyathostome larvae. AB - The efficacy of a high dose of ivermectin (1.0 mg per kg Eqvalan liquid drench) on encysted cyathostomes was tested in a controlled study using 12 adult ponies with naturally acquired cyathostome infections. Six treated ponies and six non treated controls were held in separate stalls for a period of 5 weeks. Cyathostome burdens, which included lumenal larvae, adults and encysted larvae, were determined at necropsy. The viability of encysted larvae, based on morphologic integrity, was assessed by observation of mural transillumination and by the histologic appearance of 12 larvae per pony. Efficacy against adult cyathostomes was 99.9%. Lumenal cyathostome larval numbers were reduced by 87%. Numbers of encysted cyathostome larvae, identified by transillumination of the large intestine, were reduced by 35%. However, this reduction was not statistically significant (P > 0.05) and differences in viability of encysted larvae were not observed. The data strongly indicated that ivermectin has little demonstrable effect on encysted equine cyathostomes. PMID- 8493774 TI - Intestinal neuronal dysplasia: does it exist or has it been invented? PMID- 8493775 TI - Growth hormone (GH) and prolactin (PRL) gene expression and immunoreactivity in GH- and PRL-producing human pituitary adenomas. AB - Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotroph-lactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph. PMID- 8493776 TI - Expression of beta 1 integrins in non-neoplastic mammary epithelium, fibroadenoma and carcinoma of the breast. AB - beta 1 Integrins were examined immunohistochemically in normal and mastopathic mammary glands, 12 benign tumours and 90 carcinomas of the breast using monoclonal antibodies against beta 1 and alpha 1 to alpha 6 subunits. When compared with epithelial cells of non-neoplastic mammary glands and of benign tumours, carcinoma cells showed considerable quantitative changes in the pattern of alpha 2, alpha 3 and alpha 6 subunit expression. In contrast, the distribution pattern of beta 1, alpha 1, alpha 4 and alpha 5 antigens corresponded to the situation observed in non-neoplastic mammary gland epithelium in most instances. An abnormal expression of alpha 2 was found in 71.0% of the carcinomas ranging from a remarkably low number of alpha 2-positive tumour cells in 27.5% of the cases to a complete absence of the alpha 2 molecule in 43.5% of the carcinomas. Of the carcinomas 39.9% exhibited quantitative changes in alpha 3 expression with an abnormally low content of alpha 3-positive neoplastic cells in 15.4% and a complete absence of this molecule in 24.5% of the cases. Expression of alpha 6 was abnormal in 73.2% of the carcinomas, consisting in a greater number of alpha 6-negative tumour cells in 31.9% and in a complete absence of alpha 6 in 41.3% of the tumours. The abnormally low expression/absence of alpha 2 and alpha 3 subunits correlated with oestrogen receptor negativity (P < 0.033 and P < 0.04, respectively). In addition, abnormally low expression/absence of alpha 2 correlated with poor differentiation of the tumours (P < 0.014). The quantitative changes in the expression pattern of beta 1-associated alpha subunits in breast carcinomas may cause a disturbed cell-cell and/or cell-matrix interaction that increases the invasive and migratory property of the tumour cells. PMID- 8493777 TI - Papillary cystic tumours of the pancreas: an analysis by nuclear morphometry. AB - Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 microns, 2.21 microns, 30.45 microns2, 36.41%) were all significantly larger than those of the non metastasizing PCT (6.34 microns, 1.59 microns, 23.66 microns2, 23.74%; P < 0.005, P < 0.005, P < 0.005, P < 0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate. PMID- 8493778 TI - Expression of cell adhesion molecules alpha-2, alpha-5 and alpha-6 integrin, E cadherin, N-CAM and CD-44 in renal cell carcinomas. An immunohistochemical study. AB - Renal cell carcinoma is known to metastasize early independent of tumour grade. Invasion of the renal vein plays an important role in the prognosis. Cell adhesion molecules have been investigated, including the expression of alpha-2, alpha-5, and alpha-6 integrin, E-cadherin, neural-cell adhesion molecule and CD 44 in 34 renal cell carcinomas, using the alkaline phosphatase-anti-alkaline phosphatase technique. Our results indicate a differential expression of these cell adhesion molecules (alpha-2, alpha-5 and E-cadherin) depending on histological type and tumour grade. PMID- 8493779 TI - Localized amyloidosis in squamous cell carcinoma of uterine cervix: electron microscopic features of nodular and star-like amyloid deposits. AB - An ultrastructural study of amyloid deposits in four cases of squamous cell carcinoma of uterine cervix was performed. The amyloid deposits reacted with anti keratin antiserum on frozen sections. Amyloid deposits showed nodular (4 cases) and star-like forms (3 cases). Nodular amyloid deposits were composed of slightly whorled fibrils, measuring 7-10 nm in width. Some of them contained cellular debris and thicker, more electron-dense filaments than amyloid fibrils. In three cases, filamentous tumour cells and filamentous masses were observed together with amyloid. Star-like amyloid deposits were composed of bundles of straight amyloid fibrils. Some of the tumour cells in contact with star-like amyloid deposits had deep cytoplasmic invaginations, where closely packed amyloid fibrils were arrayed in parallel fashion. In addition, a few tumour cells had membrane bound amyloid fibrils in the cytoplasm. It is suggested that nodular amyloid deposits are derived from the tumour cells through filamentous degeneration. Amyloid fibrils in star-like amyloid deposits are thought to be formed within the cytoplasm or in the vicinity of invaginated cytoplasmic membranes of the tumour cells. PMID- 8493780 TI - Parachordoma: an ultrastructural and immunohistochemical study. AB - A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6-sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells. PMID- 8493781 TI - Fetal Niemann-Pick disease type C: ultrastructural and lipid findings in liver and spleen. AB - We present the first ultrastructural study of liver and spleen from a 20-week fetus with Niemann-Pick disease type C in correlation with lipid studies of these tissues. The lipid storage pattern was characteristic of the disease and although the distribution of the lipid storage was similar to that of affected children, ultrastructural studies emphasized that many inclusions were qualitatively different. These are discussed. Concomitant with this complex lipid storage, ultrastructural evidence of cholestasis was observed and the early hyperplasia of pericanalicular microfilaments leads us to question the presence of a toxic metabolite which might induce cholestasis by acting upon microfilaments. PMID- 8493782 TI - [The obstruction syndrome in patients with bronchogenic carcinoma]. AB - In the period 1985-1990, 760 patients with bronchogenic carcinoma have been examined and treated at the Clinic of Lung Diseases of the Military Medical Academy. Obstruction syndrome was found in 64% of patients of whom 21% with severe obstruction. Pulmonary insufficiency, most commonly of milder, partial type, was found in 19% of patients. Due to the limited lung function as a consequence of chronic obstructive lung disease (COLD) 45 patients with locally demarcated tumours were not operated, surgical resection was not possible. In the operated patients with obstruction syndrome the risk of postoperative complications was increased. COLD and limited lung function most commonly had not been the obstacle for application of radiotherapy of bronchogenic carcinoma. PMID- 8493783 TI - [Pharmacokinetics of the oxime, HI-6, in patients with acute organophosphorus insecticide poisoning]. AB - The results of the study of the pharmacokinetics of a new cholinesterase reactivator--the HI-6 oxime in patients with acute organophosphorus insecticide poisoning and results of effects of its way of application on the rapidity and efficacy of treatment are reported. The results have shown that pharmacokinetic behaviour of HI-6 oxime has been changed during poisoning but these changes have not caused additional risks or changes in the accepted regime of drug dosage. Also, there have been no significant differences in efficacy and speed of reactivation of acetylcholinesterase inhibited by organophosphates when HI-6 is applied in the form of permanent intravenous infusion or repeated intramuscular injections. PMID- 8493784 TI - [Early results of arthroscopic meniscectomy of the knee]. AB - The results of 218 arthroscopic meniscectomies of the knee in 200 patients are reported. There were 188 men and 12 women. There have been performed 141 medial, 41 lateral and 18 bilateral meniscectomies. The tear in the form of "bucket handle" was dominated and it was found in 140 cases of which 76 were incarcerated. The postoperative hospitalization lasted 1 to 3 days. No infections of arthroscopic operative wounds were found. Three synovitis with effusions were found. PMID- 8493785 TI - [Analysis of bacterial flora in burn patients]. AB - Bacterial flora of burn wound smears and hemocultures of 25 patients with burns have been followed up and analysed in the period of one year. Pseudomonas auruginosa have been most commonly isolated from burn wound smears, in 406 (5.6%) and Staphylococcus aureus, in 371 (47.14) samples. The most important hemoculture isolates has been Staphylococcus aureus found in 34 (57.6%) of samples. One multiresistant strain of Staphylococcus aureus represented 91% of all Staphylococcus aureus strains isolated from hemocultures and 84% from burn wound smears. Serologic and pyocin typing of Pseudomonas auruginosa proved the presence of several epidemic strains. PMID- 8493786 TI - [Physico-chemical characteristics of submandibular salivary secretions in patients with peripheral paralysis of the facial nerve]. AB - In 53 patients with peripheral facial palsy divided in the definite groups there have been continually followed up changes in the physico-chemical features of saliva of the submandibular salivary glands and the motor function of the mimic musculature in the course of a year-observation of pH, osmotic pressure and electrolote secretion. The reduction of Na+ and CO2 secretion resulted in the low values of pH and osmotic pressure in all saliva samples at the site of lesion. The degree of this reduction has been shown to be in the direct relationship with the severity of the nerve lesion and its final outcome. PMID- 8493787 TI - [HIV infection in Vojvodina]. AB - The study of HIV infection in the population of Vojvodina was carried out in the period 1985-1991. The results obtained by the seroepidemiologic examination of some epidemiologically important groups of populations and recorded cases of AIDS are compared. It has been found that the seroepidemiologic examinations, in spite of some shortcomings, provide a more reliable insight into the epidemiologic situation of HIV infection. PMID- 8493788 TI - [Hemangiopericytoma of the lungs]. AB - Six patients, three women and 3 men with lung hemangiopericytoma treated at the Military Medical Academy in the period 1971-1991 are reported. The youngest patient was 20 years, the oldest 69 years. Surgical treatment was performed in all patients, 3 lobectomies, one bilobectomy, one wedge resection and one extirpation. Multiple hemangiopericytoma was found in one patient which consisted of three separate tumours in the right lung. The other had solitary lesions. Malignant hemangiopericytoma, was found in 4 patients, one of them had metastases in the mediastinal lymphatic glands. Four patients are alive and are under control for nine years in the average without signs of recurrence. PMID- 8493789 TI - [Therapy of dysseborrheic dermatitis with ketoconazole]. AB - Thirty patients with dysseborrhoeic dermatitis (DD) of the scalp, 27 men and 3 women, were treated with 2% ketokonazole gel prepared in the Institute of Pharmacy of the M.M.A. Therapeutical effects was assessed on the basis of the objective clinical signs (erythema, desquamation) and subjective feeling of itching. Four weeks after the beginning of treatment the complete therapeutic response was obtained in 80% of patients (withdrawal of all clinical signs and subjective symptoms), good response was achieved in 16.6% and satisfying in 3.33% of patients. In no patients the preparation was without clinically evident effects. After cessation of the therapy, remission lasted from 2 to 12 weeks (mean, 4 weeks). The probable way of ketokonazole effect in DD is the inhibition of cytochrome P450 izoenzyme. PMID- 8493790 TI - [Onychomycosis]. PMID- 8493791 TI - [Use of colloidal gold in electron microscopy]. PMID- 8493792 TI - [Transesophageal echocardiography in the diagnosis of infective endocarditis]. PMID- 8493793 TI - Commonwealth Caribbean Medical Research Council. Proceedings of the 38th scientific meeting, April 21-24, 1993 Port-of-Spain, Trinidad. Abstracts. PMID- 8493794 TI - An overview of structural adjustment in the Caribbean. PMID- 8493795 TI - Structural adjustment--the impact on health. PMID- 8493796 TI - The need for family planning services for women delivering with little or no prenatal care. PMID- 8493797 TI - Gender, recovery from late life heart attack, and medical care. AB - It has only recently been recognized that there are significant gender effects on heart disease and that women face increasing risks as they age. A longitudinal study of 246 older myocardial infarction (MI) patients included a 1/3 sample of women. Findings indicate that over the first post-MI year, women had greater risk of death, cardiac distress and reinfarction. Cardiac symptoms of men declined while those of women increased. Several medical care and social disadvantages were found among the post-MI women, including less aggressive cardiac care. Furthermore, since morbidity and mortality were related to medical care and social disadvantages, the results support gender-age stratification theories. PMID- 8493798 TI - The health of women married to men in regular army service: women who cannot afford to be ill. AB - The health, distress, and health services utilization of 44 women married to army men was compared to those of 53 women living in the same community. Army wives were found to have less access to health promoting and maintaining resources such as social support, employment, and the "sense of coherence." Although army wives' health is not significantly different from that of the controls, they visit the family physician with their children more often. It is suggested that women who are married to army men learn to cope with instability and with limited access to salutary factors, but the lay referral system is irreplaceable. PMID- 8493799 TI - Development of a scale to measure gender-role attitudes toward breast-feeding among primiparas. AB - Women's roles have undergone rapid transformation in recent decades and appear to affect the decision to breast-feed. Research in this area has been hampered by the lack of valid instruments to measure the relevant domains of gender-role related considerations. This study developed a scale to measure gender-role attitudes toward breast-feeding in primiparous women. Ninety-one married women, recruited during childbirth education classes in the Chicago metropolitan area, were surveyed by mail at eight weeks postpartum regarding their experiences as new mothers. Questionnaire items measuring infant feeding method (breast-feeding, bottle feeding) and attitudes toward breast-feeding were developed specifically for this investigation. Validity and reliability were assessed by structural equations analysis using LISREL. The LISREL fit statistics supported a one factor measurement model and combining the six items into a scale. Reliability analysis yielded a standardized alpha coefficient of .74. If results of future research are promising, the scale could be used to target new mothers with multiple roles for education and support and to evaluate interventions designed to promote positive breast-feeding attitudes and behavior. PMID- 8493800 TI - Women and AIDS: social determinants of sex-related activities. AB - Female sexual partners of injection drug users are at risk for AIDS because of their association with street drug cultures and all their concomitant risks, including their own non-injecting drug use. This study examines a model of the social determinants of HIV-associated sexual risk behaviors. Multiple linear regression analysis was used to analyze the data for 207 female sexual partners who had never injected drugs. The findings show that crack cocaine use is the strongest contributor to the model, which explains fourteen percent of the variance of sexual risk behavior. The findings suggest that the risks associated with sexual practices are much greater for crack cocaine users than among non users of crack. PMID- 8493801 TI - Gender differences in perception of risk associated with alcohol and drug use among college students. AB - Gender differences in perception of risk associated with use of alcohol and other drugs were assessed among a sample of 1,244 undergraduates at a major Pacific Northwest university. Reexamination of data from a self-administered questionnaire revealed that females were more likely than males to perceive greater risk with use of alcohol and other drugs. In particular, female perceptions of risk were significantly different from males (P < .001) for most levels of alcohol use and for perception of risk for occasional use of psychedelics, heroin, and diet pills. Our findings suggest the need for continued gender-specific research (and health education) in substance abuse prevention. PMID- 8493802 TI - Prevalence of latent portasystemic encephalopathy in an unselected population of patients with liver cirrhosis in general practice. AB - To evaluate the prevalence of latent PSE in unselected ambulatory patients with liver cirrhosis practicing physicians were asked to perform two non instrumental psychometric tests (number connection test and line tracing test) on patients with clinical signs of liver cirrhosis and portal hypertension. Tests were repeated after 8 weeks of treatment with Lactulose in those patients considered to have latent PSE at the initial evaluation. 296 physicians tested a total of 783 patients, 771 of these could be evaluated. 551 patients (71.5%) were considered to have latent PSE. There was a significant correlation between psychometric test results and biochemical parameters related to liver function. Repeat testing after 8 weeks treatment with Lactulose revealed definite improvement of psychometric test results in 88% of the patients. At the final evaluation only about 30% of the patients fulfilled the criteria of latent PSE. There was a statistically significant albeit weak correlation between changes in biochemical parameters and psychometric improvement. Psychometric testing with simple non instrumental tests proved to be practicable in the office setting. PMID- 8493803 TI - [Valine and branched-chain amino acids in the treatment of hepatic encephalopathy]. AB - We studied the effects of infusion of a liver adapted amino acid solution (Amino Mel hepa: Group A) versus a liver adapted amino acid solution plus L-valine (Amino-Mel hepa + L-valine: Group B) in 30 patients with decompensated liver cirrhosis with coma. Each 15 patients were randomly allocated to the group A and B, respectively. Both regimens included the infusion of glucose and fat, further supplementation of vitamins and trace elements in addition to the amino acid solution. The results of this study show that in patients with advanced stage of hepatic coma a valine increased supply of branched chain amino acids neither influences the course of the disease nor the death rate. The prognosis of patients with this disease is mainly determined by liver function and accompanying complications. PMID- 8493804 TI - [Analysis of breath hydrogen (H2) in diagnosis of gastrointestinal function: validation of a pocket breath H2 test analyzer]. AB - Breath hydrogen (H2) analysis, as used in gastroenterologic function tests, requires a stationary analysis system equipped with a gaschromatograph or an electrochemical sensor cell. Now a portable breath H2-analyzer has been miniaturized to pocket size (104 mm x 62 mm x 29 mm). The application of this device in clinical practice has been assessed in comparison to the standard GMI exhaled monitor. The pocket analyzer showed a linear response to standards with H2-concentrations ranging from 0-100 ppm (n = 7), which was not different from the GMI-apparatus. The correlation of both methods during clinical application (lactose tolerance tests, mouth-to-coecum transit time determined with lactulose) was excellent (Y = 1.08 X + 0.96; r = 0.959). Using the new device, both, analysis (3 s vs. 90 s) and the reset-time (43 s vs. 140 s) were shorter whereas calibration was more feasible with the GMI-apparatus. It is concluded, that the considerably cheaper pocket-sized breath H2-analyzer is as precise and sensitive as the GMI-exhaled monitor, and thus presents a valid alternative for H2-breath tests. PMID- 8493805 TI - [Cimetidine in treatment of acute intermittent porphyria]. AB - Two female patients with repeated exacerbations of acute intermittent porphyria (20 exacerbations in 44 and 5 in 34 months, respectively) were treated with cimetidine (2 x 400 mg/d) over 4 months. Therapeutical aim of the medication was to prevent further porphyria manifestations. In contrast to previous casuistic reports and experimental studies in laboratory animals cimetidine did not stabilize porphyrin biosynthesis. One patient had an acute attack during the period of treatment, while the other had no further exacerbations. However, cimetidine did not worsen the clinical course of our patients either and therefore can safely be applied as an H2-antagonist in patients with acute intermittent porphyria. While administration of glucose and heme-preparations is considered to be an effective form of therapy for the acute episodes, long lasting as well as prophylactic therapies in order to stabilize the period of remission are not known so far. PMID- 8493806 TI - [Endoscopic pseudocysto-gastric drainage involving the stomach after Billroth II operation]. AB - A 45 years old female patient developed a large pseudocyst after an acute pancreatitis in 1987. In 1982 gastric resection with Billroth's anastomosis was performed. The patient underwent surgical internal and percutaneous external drainage in 1988, which both resulted unsuccessfully. The current admission was due to a complete occlusion of the gastric anastomosis, induced by a recurrent pseudocyst of 9.2 x 7.3 cm in diameter. Endoscopically guided pseudocysto-gastric drainage by means of electrocauterization was successful with nearly complete evacuation. PMID- 8493807 TI - [Crohn disease: morphologic findings of extra-intestinal disease manifestations]. AB - Extraintestinal manifestations occur frequently in patients with Crohn's disease. The spectrum of extraintestinal symptoms reported associated with Crohn's disease involves many organ systems. Commonly recognized extraintestinal manifestations include dermatologic, oral, ocular, skeletal, vascular, hepatobiliary, pancreatic, and pulmonary. Morphological findings on extraintestinal manifestations (erythema nodosum, pyoderma gangrenosum, erythrodermia- granulomatous periostitis and synovitis--granulomatous sialadenitis, aphthous stomatitis--fibrous alveolitis) in Crohn's disease are reported and discussed. PMID- 8493808 TI - [Diabetes mellitus after acute necrotizing pancreatitis: what is the cause?]. PMID- 8493809 TI - [Liver transplantation in HBsAg-positive patients: does preventive immune treatment improve prognosis?]. PMID- 8493810 TI - [Abstracts from the 59th annual meeting of the German Association for Cardiovascular Research. Mannheim, 15-17 April 1993]. PMID- 8493811 TI - Expression and assembly of the potato virus Y (PVY) coat protein (CP) in Escherichia coli cells. AB - A clone harboring the full-length cDNA of potato virus Y in a lambda-DASH vector under the control of a T7 promoter was introduced into Escherichia coli carrying the T7-RNA-polymerase gene on a plasmid. The viral coat protein was expressed and the product was of the same size as the corresponding mature protein in infected plants. Immunoelectronmicroscopy of transfected cell extracts revealed virus-like particles, indicating that the proteins involved in its processing and the viral coat protein retained their native activity. PMID- 8493812 TI - Genetic and antigenic analyses of influenza A (H1N1) viruses, 1986-1991. AB - Eighteen strains of human influenza A (H1N1) viruses isolated between August 1986 and January 1991 were analyzed in this study. Examination of the total viral genome of 12 strains by T1 mapping revealed that considerable genetic heterogeneity exists among these viruses. Partial sequencing of each of the non HA RNA segments of 4 viruses having divergent T1 oligonucleotide maps indicated that only one was a reassortant virus that had genes from both the influenza A (H1N1) and (H3N2) subtypes. This reassortant obtained its PB2 gene from a virus of the H3N2 subtype and the other 7 RNA segments from an H1N1 parent. Sequencing studies of the HA1 domains of the hemagglutinin (HA) genes of these 18 strains revealed that although these viruses are antigenically similar to the reference strains A/Taiwan/1/86 and A/Singapore/6/86, 7 conserved amino acid substitutions that are shared by recently isolated H1N1 viruses have occurred in the main stream of evolution of the H1N1 subtype. Our data indicate that: (1) Genetic reassortment continues to contribute to genetic variability of H1N1 viruses. (2) Genetic variants of non-reassortant H1N1 viruses are co-circulating in the world. (3) The HA's of recent H1N1 viruses are related to those of the 1986 reference strains. (4) Although there has been little detectable antigenic variability, the HA genes of human epidemic influenza A (H1N1) viruses have continued to evolve at an evolutionary rate similar to that for the H1N1 and H3N2 viruses analyzed previously. PMID- 8493813 TI - Temporal expression and immunogold localization of Plodia interpunctella granulosis virus structural proteins. AB - Monospecific antisera were produced against four structural proteins (VP12, VP17, VP31, and granulin) of the Plodia interpunctella granulosis virus using polypeptides derived by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or acid extraction. The antisera were shown to be specific on immunoblots of SDS PAGE separated granulosis virus and were further used to detect structural proteins in infected fat body lysates. Immunoblots of fat body lysates from early stages of infection indicated that VP12, VP17, VP31, and granulin were expressed by 2.5 days post-infection. Immunogold labeling of the virus using the monospecific antisera and electron microscopy confirmed earlier reports that granulin is located in the protein matrix, V17 is an envelope protein, and VP31 is a capsid protein. PMID- 8493814 TI - [The nature of the genotype and heredity]. AB - The term "genotype" is used for both hereditary information and its substantial bearer. The most important property of the information is relatively of its content which means very weak dependence on properties of the information substantial bearer (genotype of the second meaning) and very strong dependence on properties of the information recipient. Hereditary information (genotype in the first meaning) is addressed to the ontogenesis system, that is, to phenotype. From this it follows: 1) The genotype content is determined not so much by properties of its substantial bearer as by properties of the phenotype to which it is addressed; 2) Certainty of the genotype content depends not so much on stability of its elements, genes, as on stability of the phenotype of adaptive norm; 3) Genotype possess certain content only for a phenotype inherited from the ontogeny of other (maternal) organism or from a previous ontogenetic stage of the same organism; 4) Genotype (and this is true for any hereditary information of an organism) can not be localized in the primary structures of the nucleic acids. It is an aspect of phenotype and not a part thereof and, in this sense, does not possess independent being; 5) Each element of the phenotype, including genotype, relative to its other elements, is both recipient and bearer of hereditary information; 6) Genotype, as genetic code, is specialized but, not the only, "organ" of storing and transferring of hereditary information; 7) There is no two identical genotypes existing in nature; 8) The only operational definition of the genotype is its treating as genetic information localized in one or several loci; 9) Rather strong relation between certain symbols of genetic code (genes) and certain phenotypic characters reflects stability of reactional system of adaptive norm; 10) High semantic university of some symbols of genetic code indicates deep phylogenetic unity of all existing organisms; 11) Biological sense of structural separateness of the genotype within phenotype is creating and supporting of an information pool undestroyable during ontogenetic development; 12) All and only living systems possess reciprocally determining processes of individual and historic development; 13) Heredity, as an ability of descendants to reproduce safely in their ontogeneses the properties of their ancestors is an integral undecomposable (more exactly, decomposable but for operational purposes) property of the life. There is no and could not be any "heredity substance, as there is no and could not be an "information substance". PMID- 8493815 TI - [A quantitative analysis of the effect of the initial conditions on the results of phylogenetic reconstructions]. AB - Parameters of character description (homology, coding, weighting, ordering), of the context (outgroup and ingroup membership) belong to initial conditions of phylogenetic reconstructions. A principal possibility for the effects of the parameters on the results of these reconstructions to be evaluated numerically is shown. An algorithm of respective procedure is outlined which is based on combination of cladistic, principal component and dispersion (MANOVA) analyses. A study case is morphological diversity of mastoid bulla in the rodent families Gerbillidae, Dipodidae s. lato, Gliridae. The principal idea of the approach outlined is, first, to produce a set of cladograms under variable conditions determined by arbitrary altering the above parameters. Diversity of topology of these cladograms represented by respective distance matrixes is subsequently analyzed by MANOVA, the above parameters being treated as independent variables. This gives strictly quantitative and mutually commensurable estimates of the parameters influence on the topology of cladograms. It is shown that homology is the most and ordering is the least influential among character description parameters. Important effect of the context parameters is shown, as well. PMID- 8493816 TI - [Toxicology of the synthetic antioxidants BHA and BHT in comparison with the natural antioxidant vitamin E]. AB - The toxicology of the food preservatives butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT) as well as the naturally occurring vitamin E (alpha tocopherol) is described. In high dosages all three compounds induce in animals impairment of blood clotting, which can be explained by an antagonism with vitamin K. Specific toxic effects to the lung have only been observed with BHT. The other described toxic effects of BHA and BHT are less characteristic and often occur only after high dosage and long-term treatment. However, BHA induces in animals tumours of the forestomach, which are dose dependent, whereas BHT induces liver tumours in long-term experiments. Because there is no indication of genotoxicity of BHA and BHT, all published findings agree with the fact that BHA and BHT are tumour promoters. In contrast to BHA and BHT, vitamin E is not carcinogenic. On the other hand, all three antioxidants have also anticarcinogenic properties. The intake of the necessary high doses as for these effects are, however, contraindicated with BHA and BHT because of their carcinogenic effects. The present overview concludes that the concentrations of BHA and BHT nowadays used in food, drugs and cosmetics are probably harmless. In addition, vitamin E can also be used in higher doses without the occurrence of adverse effects. PMID- 8493817 TI - Ultrasonication of lamb skeletal muscle fibres enhances postmortem proteolysis. AB - The effect of ultrasound upon the postmortem proteolytic activity of muscle fibres was investigated. As a preliminary result it was demonstrated that ultrasonication released lysosomal enzymes from liver cells while cell membranes suffered little damage. Proteolysis brought about by endogenous proteinases after 2 days of fibre storage at 4 degrees C was assessed by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Ultrasonic treatment of fibres enhanced proteolytic activity, as shown by the increased intensity of 30 kDa region degradation bands. A distinct change featuring sonicated fibres was the degradation of an 87-kDa protein and the appearance of an 83-kDa peptide. Cell damage was not very extensive, although it depended upon ultrasonication and fibre conditions. PMID- 8493818 TI - Primary structures of proteinase inhibitors from Phaseolus vulgaris var. nanus (cv. Borlotto). AB - The primary structures of two trypsin-chymotrypsin inhibitors from Phaseolus vulgaris var. nanus (bush bean, cv. Borlotto), PVI-3(2) und PVI-4, were derived from automated Edman degradation data, amino acid composition and manual Edman degradation results of enzymatic fragments and homology with other Bowman-Birk type proteinase inhibitors. The highest degrees of homology were observed between PVI-3(2) or PVI-4 and the trypsin-chymotrypsin inhibitors from lima beans (LBI I, IV and IV', 86%), black-eyed peas (BTCI, 81%), and, in part, adzuki beans (ABI I, II and II', 74-77%). Similarly, the primary structure of the trypsin-elastase inhibitor from the same source, PVI-3(1), was deduced which showed highest homology with that of the trypsin-elastase inhibitor GBI II from garden beans (92%), followed by GBI II' from garden beans (86%) and C-II from soybeans (71%). In contrast, homology between PVI-3(2) and PVI-4 on the one hand and PVI-3(1) on the other was relatively low (61%). PMID- 8493819 TI - [Multiple diagnoses and stresses in children of primary school age]. AB - The study was conducted to assess the consequences of multiple diagnoses and handicaps in children aged 6 to 8 years. Children were considered to be "multiply handicapped" if they suffered from two or more disorders or impairments included in the Multi-axial Classification Scheme. To this end children in special schools were compared with a random sample of children from three communities in Bavaria. As expected, all prevalences found in the population of children from special schools were substantially higher than those found in the random sample. Furthermore, the proportion of children with multiple handicaps in the special schools far exceeded what one would have expected based on the findings for the random sample. Most of the disturbances did not differ in respect to their comorbidity. But the mentally retarded children in the special schools were all "multiply handicapped". The importance of "multiple handicaps" for the assignment to special schools is discussed, as are the implications for the planning of services. PMID- 8493820 TI - [Trance states--a case report]. AB - For the first time, trance states have been included in the International Classification (ICD-10) as a separate identity. The case of a 13-year-old boy is presented and the diagnostic process discussed especially the differentiation between trance states and epilepsy. Psychotherapy and the in-patient treatment course are described including the factors facilitating a positive outcome. PMID- 8493821 TI - [Self-manipulated disease and Munchausen syndrome in adolescents. A case report]. AB - In recent years factitious disorders have gained increasing significance in all medical specialties although in child psychiatry publications on this topic are rare. In this article these and other somatoform disorders are discussed with reference to a case report on a 14-year-old girl. Psychodynamic aspects of this syndrome are presented and differentiated from simulation. Conversion syndromes and hysterical neurosis and comparisons are made with other publications on this topic. Treatment of these patients, who repeatedly succeed in subjecting themselves to invasive and sophisticated diagnostic procedures is difficult because of minimal compliance. The prognosis is affected by the extent to which changes in personality structure and development of alternative problem-solving mechanisms can be achieved. PMID- 8493822 TI - [Theoretical and empirical concepts of psychosomatic disorders: a review]. PMID- 8493823 TI - [Serotonergic antidepressants--indications for treating children and adolescents exemplified by fluoxetine and clomipramine]. PMID- 8493824 TI - [Diagnosis of stressful life events in clinical routine practice using a (half) standardized interview]. AB - 50 in-patients and 50 out-patients were assessed with a semi-structured interview based on the revised version of axis V (abnormal psychosocial situations) of the Multi-axial Classification Scheme. The interviewer was not acquainted with the patient's history. The information acquired during in-patient treatment was comparable to that obtained by interview, whereas during out-patient treatment, less information with lower reliability was obtained than on the interview. The study also shows that certain psychosocial factors can be identified better by interview and others by clinical assessment. PMID- 8493825 TI - [New aspects of parenteral nutrition of septic patients]. AB - A major goal of this review article is to show that nutritional physiology in normal man is rather different from patients bearing an inflammatory response. Known nutrients and a variety of energy sources reveal pharmacological actions during such metabolic circumstances. An understand of the pathophysiologic state of sepsis is essential for adequate nutritional support especially in this patient population. PMID- 8493826 TI - [Surgical revascularization in patients with acute myocardial infarction]. AB - This retrospective study was done to assess the results of emergency revascularization in patients with acute myocardial infarction. In addition, the influence of the mode of reperfusion was investigated in terms of morbidity and mortality. Between January 1987 and May 1992, 75 consecutive patients with acute coronary occlusion (in 87% PTCA-failure) received one of two different reperfusion protocols during emergency aortocoronary bypass operation. In 36 patients, the reperfusate was normal blood given at systemic pressure (uncontrolled reperfusion); in 39 patients, the ischemic area was initially reperfused for 20 minutes with a blood cardioplegic solution (substrate-enriched, hyperosmolar, hypocalcemic, alkalotic, diltiazem-enriched) given at 37 degrees C and at a perfusion pressure of 50 mmHg. Thereafter, the heart was kept in the beating empty state for 30 minutes before extra-corporeal circulation was discontinued (controlled reperfusion). Regional contractility (echocardiography, radionuclide ventriculography), electrocardiogram (ECG), release of creatine kinase and MB-isoenzyme of creatine kinase as well as hospital mortality were assessed. Quantification of regional contractility was done with a scoring system from 0 (normokinesis) to 4 (dyskinesis). Data are expressed as mean +/- standard error of the mean (SEM). Both groups were well matched for age, sex, and the distribution of the occluded artery. In the controlled reperfusion group, there was a higher incidence of additional significant stenosis (2.2 +/- 0.1 vs 1.7 +/- 0.1) and cardiogenic shock (36% vs 17%). Furthermore, the interval between coronary occlusion and reperfusion was longer in the controlled reperfusion group (4.1 +/- 0.3 vs 3.3 +/- 0.3 hrs; p > 0.05). Regional contractility returned to normal after controlled reperfusion (score 0.8 +/- 0.2; normokinesis = 0, slight hypokinesis = 1). In contrast, regional contractility remained depressed severely after uncontrolled reperfusion with normal blood (score 1.5 +/- 0.3; p < 0.05). Enzyme release and ECG-changes were similar in both groups postoperatively. While only 2 of 39 patients died in the controlled reperfusion group (5.1%), mortality increased to 11.1% (4/36) if normal blood is used as the primary reperfusate. Our data show, that the surgical revascularization during acute myocardial infarction can be performed with acceptable mortality and morbidity rates. Further improvement of the results can be obtained if controlled regional reperfusion for the previously ischemic area is used. PMID- 8493827 TI - [Perioperative risk factors in esophageal cancer: a retrospective study of independent variables]. AB - The postoperative outcome of 127 patients with an esophageal carcinoma was investigated retrospectively, to identify independent factors for the perioperative mortality (hospital mortality). Chi-square single factor analysis was employed to test 35 independent variables, in a second analysis stepwise logistic regression was used to determine the factors correlating with the morality. In 41 patients the esophagus was resected by a thoraco-abdominal approach, in 86 by blunt dissection. The hospital mortality was 17.3%, the 30-day mortality 12.6%. Single factor analysis revealed a significant correlation with the variable smoking (p < 0.003), post-operative morbidity (p < 0.008), CEA (p < 0.02), time of operation (p < 0.02) and surgical procedures (p < 0.02). The influence of the surgeon's experience was significant. In the stepwise logistic regression the duration of operation (p < 0.0039), the surgical procedures (p < 0.016), and the units of blood (p < 0.03) were correlated with mortality. The logistic regression showed a significant increase of mortality for the thoracoabdominal approach with increasing duration of the operation. The estimation of survival time according to Kaplan and Meier revealed a significant correlation with the stage of the tumor, but not with the surgical procedure. PMID- 8493828 TI - [Diagnosis and therapy of splenic rupture in severe polytrauma]. AB - In the last 10 years 57 polytraumatized patients were operated on ruptures of the spleen after blunt abdominal trauma. Sonography was used as a reliable method for the decision to an operative treatment. Every spleen that was ruptured grade I and II was primarily preserved by fibrin sealant or together with collagen haemostatic felt. In ruptures of the spleen grade III and IV we preferred the splenectomy. Only in one child with rupture of the spleen grade III preservation of the spleen was achieved by capsular sutures. PMID- 8493829 TI - [Differentiated therapy of proximal femoral fractures]. AB - The operative therapy of 95 proximal femur fractures is reported, which were treated in the Kreiskrankenhaus St. Ingbert/Saar in the time from January 1st 1990 to June 30th 1991. Femoral neck fractures mainly were treated operatively by endoprosthetic replacement with hemiarthroplasty or hip total endoprosthesis. For per- to subtrochanteric femur fractures the use of the dynamic hip screw (DHS) was the treatment of choice, partly with screwing up the trochanter minor, cerclage of the trochanter major and/or with stabilization by bone cement in addition. Despite of a very high average age of the patients and a high rate of mostly severe basic illness for 80% of the fractures a sufficient stability was achieved to allow full weight bearing. 76.8% of the patients could be discharged directly from the surgical treatment. The therapeutic procedure is compared with the recommendations found in the literature. Different conceptions are discussed. PMID- 8493830 TI - [Rate of recurrence in Bassini inguinal hernia operation]. AB - In this paper it is tried to give an answer whether Bassini-plastic as compared to the excellent results of Shouldice operation should be further performed. In a consecutive series of 197 Bassini operations from 1982-1986 we found after a mean follow up time of 6.8 years a 3.2% recurrency rate. We suggest therefore that Bassini operation may be carried out furthermore. PMID- 8493831 TI - [Microcirculation of the liver in hemorrhagic shock in the rat and its significance for energy metabolism and function]. AB - INTRODUCTION: Shock induced microcirculatory failure is proposed to be causative for the impairment of hepatic function, which contributes to the development of multiple organ failure. In order to quantify the interrelation between hepatic microcirculatory disturbances and organ dysfunction, we have analyzed hepatic microcirculation (in vivo microscopy), energy metabolism (ketone body ratio) and liver excretory function (bile flow) during hemorrhagic shock in rats. METHODS: Under chloralose anesthesia and mechanical ventilation Sprague-Dawley rats (n = 6) were laparotomized and the left liver lobe was exteriorized for in vivo fluorescence microscopy. Sinusoidal perfusion was assessed after i.v. injection of Na-fluorescein (2 mumol.kg-1), in vivo staining of white blood cells by Rhodamin-6G (0.1 mumol.kg-1 i.v.) enabled for analysis of leukocyte-endothelium interaction. Erythrocyte flux was measured by means of laser Doppler flowmetry. Hepatic function was estimated by measurement of bile flow via cannulation of the common bile duct. Ketone body ratio (acetoacetate/beta-hydroxybutyrate, Ac Ac/beta-OHB) was measured spectrophotometrically from arterial blood and served as indicator of hepatic energy metabolism (n = 12). After baseline recordings hemorrhagic shock (MAP: 40 mmHG) was induced by blood withdrawal and maintained for a total of 2 h. Measurements were performed during baseline as well as 1 h and 2 h after induction of hemorrhage. RESULTS: After 1 h and 2 h of hemorrhagic shock sinusoidal perfusion was found markedly impaired (p < 0.05) from 100% (baseline) to 78.3 +/- 2.4% and 60.9 +/- 13.4%, accompanied by a significant fall of erythrocyte flux to 52 +/- 2% and 46 +/- 4% (p < 0.05). Leukocyte velocity was significantly (p < 0.05) reduced both in sinusoids and in postsinusoidal venules, while leukocyte adherence to the endothelial lining cells was found increased (sinusoids: 183.2 +/- 55.6% and 178.8 +/- 39.0% (p < 0.05); postsinusoidal venules: 232.4 +/- 43.1% and 297.6 +/- 65.8% (p < 0.05)). In addition, 2 h of hemorrhagic shock caused an increase of beta-OHB, while Ac-Ac levels remained unchanged. This resulted in a significant reduction of ketone body ratio. Concomitantly, bile production was significantly decreased from 20.8 +/- 2.9 microliters.min-1 during control to 6.1 +/- 1.0 microliter.min-1 after 2 h of shock (p < 0.05). The alteration of energy metabolism and the impairment of bile flow correlated significantly (p < 0.01) with the extent of microcirculatory disturbances. CONCLUSION: Liver microcirculation in hemorrhagic shock is characterized by sinusoidal perfusion failure with a reduction of erythrocyte flux, leukocyte velocity and enhancement of leukocyte adherence to the microvascular endothelial lining. Correlation of the impairment of energy metabolism and liver dysfunction with these microcirculatory disturbances may indicate their crucial role in the development of shock-induced organ failure. PMID- 8493832 TI - [Inflammatory intestinal tumor as a cause of thrombocytopenia]. AB - The acquired thrombocytopenia is part of a large number of diseases caused by a variety of different factors. Besides the classical failure of bone marrow proliferation respectively the replacement of the bone marrow with malignant cells, there are immunological disorders and many substances which may cause thrombocytopenia. The diagnosis of an "idiopathic thrombocytopenia" is sometimes posed even at the end of intensive diagnostic efforts. Possibly a benign neoplasia is also to cause a massive decrease of thrombocytes. We observed preoperatively in one patient with extensive stenosis of the sigma, caused by an inflammatory tumor a thrombocytopenia with a level under 50,000/ml. A normalization in thrombocyte blood counts appeared spontaneously after tumor resection. PMID- 8493833 TI - [Spontaneous rupture of the urinary bladder after radiotherapy]. AB - The spontaneous intraperitoneal rupture of the urinary bladder is an extremely rare life threatening event. There are often difficulties in making the diagnosis. A case of spontaneous rupture of the bladder 6 years after radiation therapy for uterus cancer is reported. An early surgical exploration including the closing of the rupture, peritoneal lavage and continuous vesical drainage will save the life of the patient. PMID- 8493834 TI - Problems in the balloon occlusion of aneurysms. AB - From 1987-1991 we performed 20 balloon occlusions in 15 patients with intracranial aneurysms. In 9 patients procedures were technically successful however long term complications included three deaths. In spite of the advancements in the balloon catheter technology fatalities occur restricting the use of percutaneous balloon occlusion to patients with unclippable aneurysms. PMID- 8493835 TI - Haemangiopericytoma and meningioma presenting clinically with intracranial haemorrhage: report of three cases and review of the literature. AB - We report one case of haemangiopericytoma and two cases of meningioma whose presenting symptom was subarachnoid haemorrhage. We discuss the etiopathogenetic factors involved in this rare mode of onset in the light of the published work. PMID- 8493836 TI - [Localization of frontobasal traumatic cerebrospinal fluid fistulas. Comparison of radiologic and surgical findings]. AB - Computed tomographic and surgical findings were compared in 30 patients with traumatic frontobasal cerebrospinal fluid fistula. Radiological signs were extension of fractures of the rhinobasis, localized opacification of paranasal sinuses, and localized intracranial air collections. Exact localization of dural tears was only possible in about half of all patients (16 of 30). In conclusion there must be surgical inspection of all fractures of the skull base, and only isolated injuries could be treated by selective surgery. PMID- 8493837 TI - Isolated parts of the ventricular system. AB - It has been known for years that patients with shunted hydrocephalus can develop an isolated fourth ventricle with or without signs of cerebellar dysfunction. It has also been reported about other isolated parts of the ventricular system following treatment of communicating hydrocephalus. We observed three children, two with an isolated fourth ventricle and one with an isolated third ventricle. The clinical appearance, the pathogenesis and treatment will be discussed. PMID- 8493838 TI - Giant intracranial aneurysms in children and adolescents. AB - 10 giant intracranial aneurysms in children were treated consecutively in Neurosurgical Department of Ataturk University, Erzurum, Turkey between 1985 1989. A total of 60 aneurysms of normal size were operated on in the same period. Of the ten cases 6 were male and 4 were female. All the patients were under 17 years old. In 6 cases, the onset of symptoms was sudden subarachnoid hemorrhage, in 3 cases presenting symptoms were insidious imitating a intracranial mass, and in one case, clinical manifestation was epileptic seizure. Among 6 cases with subarachnoid hemorrhage, 3 were in IV grade according to Hunt-Hess scale, 2 were in III grade and one in II grade. Angiographic localisation of the aneurysms was in the middle cerebral artery in 9 cases and in the anterior communicating artery in one case. During the operation, blood pressure was not lowered. All the patients were operated on with normal blood pressure without hypotension. In 4 cases, intramural thrombosis was detected. The necks of aneurysms were occluded by suitable clips. The aneurysms were excised in 4 cases after clipping. One patient died in the early postoperative period, and 9 cases remained alive and were free of symptoms after the operation for one to 4 years. We conclude that especially giant aneurysms in children should be treated surgically without exercising hypotension during operation. PMID- 8493839 TI - [Vitreous hemorrhage after acute subarachnoid hemorrhage in cerebral aneurysm]. AB - In four cases we investigated the rare phenomenon of "Vitreous hemorrhage after rupturing of cerebral aneurysms". We try to point out the etiology and mechanisms of hemorrhage as well as to discuss diagnostic measurements and therapeutic management. PMID- 8493840 TI - In vitro evidence for multiple neuritogenic factors in the central nervous system of pulmonate molluscs. AB - Previous work has shown that neurons of the fresh water pond snails, Lymnaea and Helisoma, require soluble factors produced by neural tissues for neurite outgrowth to occur in vitro. In the present study, we show that mammalian nerve growth factor (NGF) stimulates neurite outgrowth of specific Lymnaea neurons. In contrast to motoneurons and interneurons, which show a robust dose response to NGF, no response was observed in neurosecretory cells. In an attempt to localize neuritogenic activity to specific ganglia or organs, we show that the dorsal bodies, endocrine structures of the cerebral ganglia, promote neurite outgrowth of specific neurons. In general, however, the spectrum of neurons that respond to dorsal body cell conditioned medium differs from that which respond to NGF. We conclude that Lymnaea neurons respond both to NGF and also to a separate factor derived from the dorsal body cells. PMID- 8493841 TI - In vitro connections between Lymnaea and Helisoma identified interneurons and their follower cells. AB - The mechanisms that underly the specificity of synaptic connections are poorly understood. In this study we used two homologous interneurons, the giant dopamine cell (GDC), in two species of pond snails, Lymnaea and Helisoma. We examined the ability of the Lymnaea GDC to form specific synapses with known follower or non follower cells in vitro. Similar tests were performed for the Helisoma GDC. Both of these interneurons form appropriate connections not only with homologous follower neurons, but also with follower neurons from the alternative species. These results suggest that common mechanisms of cell recognition and synapse formation exist in the nervous systems of these two different families of molluscs. PMID- 8493842 TI - Serotonin in helminths: content, synthesis, metabolism. PMID- 8493843 TI - Sensory receptors in the head of Stenostomum leucops. II. Localization of catecholaminergic histofluorescence-ultrastructure of surface receptors. AB - The ultrastructure of three types of sense receptors in the anterior end of Stenostomum leucops is described. Type I is characterized by abundant branching microvilli and ciliary rootlets but a lack of cilia. Type II possesses a short cilium with aberrant axonema. Type III has a cilium protruding from an invagination, a long rootlet and a collar of microvilli. The glyoxylic-acid induced fluorescence method reveals catecholaminergic (CA) fluorescence in surface cells of the anterior end. The relationship between the CA fluorescence and the localization of the sense receptors is discussed. PMID- 8493844 TI - Neuropeptides in sensory structures of nematodes. AB - The peptidergic innervation of sensory structures in two species of nematodes, Ascaris suum (order Ascaridida, family Ascarididae) and Cystidicola farionis (order Spirurida, family Cystidicolidae) was studied. Immunocytochemical methods were used for localization of FMRF-amide-like neuropeptides in the nervous system. Immunoreactivity to FMRF-amide, RF-amide and SALMF-amide was detected in the central nervous system of the species studied, and also in the cephalic papillary nerves, in axons of the amphids and the deirids, and in nerves innervating caudal papillae. PMID- 8493845 TI - Cell-specific effects of lead on cultured neurons of the freshwater snail Planorbarius corneus. AB - Cultures of isolated neuronal populations from the central ganglia of the gastropod mollusc Planorbarius corneus were used for testing the effects of inorganic lead. The examined parameters were cell survival, neurite outgrowth and cytoskeletal morphology. In large heterogeneous neuronal populations as obtained from a whole cerebral or pedal ganglion, the different sensitivity to lead is reflected mainly on the cell survival. The neurons belonging to the homogeneous E cluster population are more sensitive; in fact a higher percentage of them do not survive in the presence of lead. Moreover, in this neuronal cell type the neurite outgrowth is dramatically affected by lead only when the neurons are cultured on conditioned substrate. Possibly, membrane mechanisms activated for the neurite outgrowth represent a target for inorganic lead. The few neurites sprouted in presence of lead do not evidence changes in the cytoskeletal components. PMID- 8493846 TI - Acetylcholine level in the brain and other organs of the bivalve Anodonta cygnea L. and its modification by heavy metals. AB - Acetylcholine was detected and measured in the ganglia (60-80 nmol/g), in the heart (10-15 nmol/g) and in the adductor muscles (4-5 nmol/g) of the bivalve Anodonta cygnea L. using gas chromatographic determination. Treatment of the animals with low concentration of heavy metals, which cause change in the behaviour, resulted in decrease of the brain acetylcholine level. Within 7 days treatment Cu2+ caused 80 per cent, Cd2+ and Pb2+ 30 per cent reduction with varying types of recovery after wash. PMID- 8493847 TI - Free-radical damage of identified neurones in Lymnaea stagnalis. AB - We used one of the porphyrin compounds to investigate the selective sensitivity of the different neurones in network to free radical (FR) damage. In general, interneurones are much more resistant to FR damage as compared with other components of the network. PMID- 8493848 TI - Effects of general anaesthetics on cultured Lymnaea neurones. AB - In order to elucidate the mode of action of general anaesthetics we are using neurones of Lymnaea stagnalis as a model system. Neurones exhibit mainly two types of responses to anaesthetics delivered at clinical concentrations, i.e., either gradually going into quiescence or exhibiting paroxysmal depolarizing shifts (PDS). In order to determine whether these differences are due to intrinsic membrane properties or because of synaptic effects, cultured neurones are being used so that cells can be studied in isolation from any synaptic effects. Cells in culture retain their basic electrophysiological characteristics and behave in a similar manner to the applied anaesthetics as do whole brain preparations. Demonstration of PDS and quiescence in cultured neurones shows that these phenomena are due to membrane effects and not due to synaptic inputs. The effects of anaesthetics observed seem to be consistent with the suggestion that anaesthetics may influence the inward calcium current or other calcium-dependent currents. PMID- 8493849 TI - The structural multiplicity of Mytilus inhibitory peptides isolated from pulmonate molluscs. PMID- 8493850 TI - FMRFamide-related peptides isolated from the prosobranch mollusc Fusinus ferrugineus. AB - In addition to FMRFamide and FLRFamide, four FMRFamide-related peptides were isolated from the ganglia of a prosobranch mollusc, Fusinus ferrugineus. Their primary structures were ALTNDHELRFamide, LSSFVRIamide, GSLFRFamide and SSLFRFamide. PMID- 8493851 TI - Stress-induced release of octopamine in the American cockroach Periplaneta americana L. AB - After stress, changes of octopamine content were observed in the antennal heart and the retrocerebral complex of cockroaches. Only individually handled animals exposed to short and extreme stress showed an alteration in the haemolymph octopamine levels. The removal of the retrocerebral complex resulted in an elevation of the octopamine content in the haemolymph. We suppose that the corpora cardiaca are not the only source for the octopamine released into haemolymph in stress situations. PMID- 8493852 TI - Pigment-dispersing hormone immunoreactive neurons in the blowfly nervous system. AB - We could demonstrate pigment-dispersing hormone immunoreactive (PDHIR) neurons in the brain and ventral ganglia of the blowfly Phormia terraenovae. PDHIR neurons were found in the optic lobe. Their processes supply the lamina, medulla and lobula complex bilaterally. Large PDHIR cell bodies in the protocerebrum have processes in the proto- and tritocerebrum and axons to the aorta wall and foregut. Eight pairs of PDHIR neurons are found dorsally and three pairs ventrally in the fused abdominal neuromeres; one pair is located ventrally in each of the thoracic neuromeres. The ventral abdominal PDHIR neurons are efferents that innervate the hindgut. PDHIR neurons may play different functional roles as neurohormones or neuromodulators in different parts of the nervous system and its peripheral targets. PMID- 8493853 TI - Structural plasticity of an immunochemically identified set of honeybee olfactory interneurones. AB - Using a monoclonal antibody (FB 45) raised by Dr. A. Hofbauer (Wurzburg) against Drosophila brain we investigated the development and plasticity of immunoreactive cells belonging to the median and lateral antennoglomerular tracts (AGTS) in the honeybee brain. In early stages of pupal development presumed AGT immunoreactivity was detected in the diffuse central neuropil of the antennal lobe as well as in the glomeruli, which differentiate at 40% pupal development. The lateral protocerebral lobe--one target area of the AGTs--is labelled throughout pupal life whereas labelling in the calyces is first restricted to the basal ring region. Although the lips of the calyces develop in middle-aged pupae, they do not show immunoreactivity until the last day of metamorphosis. Unilateral ablation performed on pupae of different stages resulted in size reduction of the antennal lobe and fusion of glomeruli. The number of labelled somata and glomeruli in the antennal lobe were reduced on the treated side. These effects were more prominent when ablation was performed in young pupae. No differences in staining intensity at the light microscopic level were found in the calyces. Therefore a pre-embedding immunohistological approach was developed to detect AGT profiles in the mushroom body at the electron microscopic level. PMID- 8493854 TI - Biochemical characterization of a serotonergic system in the neural sheath of Helix ganglia. AB - Seasonal alterations of serotonin (5HT) as well as the release of 5HT and the presence of the synthesizing enzyme of serotonin (5HTP-decarboxylase) were investigated in the neural sheath and desheathed ganglia of Helix pomatia. It has been established that i) serotonin concentration shows a seasonal variation in the sheath, ii) serotonin is not synthesized in the neural sheath, iii) K(+) dependent serotonin release occurs only in the desheathed ganglia. PMID- 8493855 TI - Characterization of catch-relaxing peptide (CARP) immunoreactive neurons in the Helix nervous system. AB - Both small and large diameter of CARP immunoreactive neurons could be observed in the different ganglia of CNS of Helix but not in the foot musculature. The immunoreactivity is the strongest in the varicose segments of immunoreactive fibers. The present findings suggest a transmitter or modulatory role of CARP in both central and peripheral regulatory processes. PMID- 8493856 TI - Serotonergic input on identified command neurons in Helix. AB - In Helix, serotonin evokes long-lasting alteration of activity of withdrawal triggering neurons. Cell bodies of these neurones are surrounded by a dense network of serotonin-containing fibres without any synaptic membrane specializations, which confirm the suggestion on the non-synaptic, modulatory action of serotonin on the withdrawal command elements. PMID- 8493857 TI - Oculomotor nuclear pathology in amyotrophic lateral sclerosis. AB - We examined the oculomotor and/or trochlear nuclei of 27 amyotrophic lateral sclerosis (ALS) patients and 10 controls by histological and immunohistological methods. Their neurons were relatively well preserved. In 7 of 22 sporadic ALS patients (including 3/3 ALS with ophthalmoplegia) and in 4 of 5 ALS patients with dementia, some morphological changes similar to those in anterior horns (Bunina bodies, ubiquitin-positive skein-like inclusions, Lewy body-like inclusions, conglomerate inclusions and spheroids) were rarely, but clearly seen. These changes were not observed in controls. Our results suggest that the oculomotor and trochlear nuclei in ALS patients are slightly affected in a manner similar to that in the anterior horns, but the degree is less than that necessary for development of ophthalmoplegia in the majority of ALS patients. PMID- 8493858 TI - Heating of the brain to maintain normothermia during ischemia aggravates brain injury in the rat. AB - During brain ischemia temperature spontaneously declines. In animal experiments this decline is frequently prevented by stabilizing the temperature at the pre ischemic level, using an external heat source. The present study examines whether this procedure influences the severity of ischemic injury. Wistar rats were submitted to 30-min four-vessel occlusion followed by 7 days recirculation. During ischemia and the 1st h of recirculation various systemic and electrophysiological variables were recorded. Seven days after the ischemia brains were perfusion-fixed for light microscopical examination. Three brain temperature profiles were compared: spontaneous decline of brain temperature during ischemia from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5); constant brain temperature of 30 degrees C induced by selective head cooling (induced hypothermia; n = 5); and constant brain temperature of 36 degrees C induced by selective head heating (normothermia; n = 5). Core temperature was maintained constant at 37 degrees C in all groups. In spontaneous hypothermia, 19% of CA1 neurons survived after 30-min ischemia. Induced hypothermia significantly increased this percentage to 69% (P < 0.05); maintenance of brain temperature at normothermia decreased neuronal survival to 1%. Normothermia also led to morphological injury outside the vulnerable regions, an increase in mortality, marked loss of body weight and a prolongation of the electroencephalographic suppression. These findings demonstrate that stabilizing brain temperature at a constant normothermic level by an external heart source introduces an aggravating pathological element that may interfere in an unpredictable way with the manifestation or treatment of ischemic injury. PMID- 8493859 TI - Early ependymal changes in experimental hydrocephalus after mumps virus inoculation in hamsters. AB - To elucidate the pathogenesis of early ventricular dilatation in hydrocephalus, we examined early morphological changes in ependymal layers at the lateral ventricles in suckling hamsters without aqueductal stenosis 5 days after the intracerebral inoculation of mumps virus. Mumps virus antigen was detectable in all ependymal cells. The ependymal cilia had almost disappeared and only the microvilli remained. A number of supraependymal cells were also observed on the surface of the lateral ventricles. Transmission electron microscopy revealed intracytoplasmic viral-like inclusions in the infected ependymal cells. These results suggest that functional and morphological disturbances in infected ependymal cells may cause early ventricular dilatation before aqueductal stenosis occurs. PMID- 8493860 TI - Temperature effect on immunostaining of microtubule-associated protein 2 and synaptophysin after 30 minutes of forebrain ischemia in rat. AB - The regional distribution of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein synaptophysin was investigated by immunohistochemistry in brains of rats submitted to 30-min forebrain ischemia by four-vessel occlusion. The following brain temperature profiles during ischemia were compared: (1) constant brain temperature of 36 degrees C (normothermia; n = 5); (2) spontaneous temperature decline from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5) and (3) constant temperature of 30 degrees C (induced hypothermia; n = 5). Normothermia was produced by exposing the ischemic head to an external heat source, and induced hypothermia by cooling the head with liquid nitrogen vapours. Sham-operated animals were either kept at ambient temperature or exposed to the same heat source, as required for maintaining normothermia during ischemia. Seven days after sham operation or ischemia, brains were fixed by perfusion and processed for immunohistochemistry using monoclonal antibodies against MAP2 and synaptic vesicle-specific protein (synaptophysin). Normothermic ischemia resulted in complete loss of MAP2 immunostaining in the whole hippocampus, spontaneous hypothermic ischemia in complete loss of MAP2 in CA1 sector, and induced hypothermic ischemia only in variable loss of MAP2 in CA1 sector. Post-ischemic immunostaining of synaptophysin revealed a temperature dependent increase in stratum lacunosum-moleculare of CA1 sector, the density of which correlated inversely with MAP2 staining. Comparison with morphological alterations showed a close relationship between loss of MAP2 staining and histological injury. The post-ischemic activation of synaptophysin may reflect regenerative processes associated with synaptic remodelling and, therefore, is an indirect marker of the severity of ischemic injury. PMID- 8493861 TI - A morphological study of nerve biopsies from cases of multibacillary leprosy given multidrug therapy. AB - Nerve biopsies were examined from 17 cases of lepromatous leprosy given WHO recommended multidrug therapy (MDT) for 2 years. The pathological changes were assessed qualitatively and quantitatively to judge the effectiveness of MTD. The nerves varied very considerably in the severity of their lesions. Some regenerating fibres were seen in most of the nerves. In a few cases, the nerves were almost entirely populated by regenerated fibres, confirming that MTD was effective in halting the disease process within the nerve. Mycobacterium leprae showed morphological features of degenerate bacilli. Some pathological features of the lepromatous lesion are described. PMID- 8493862 TI - The distribution of amyloid plaques in the cerebellum and brain stem in Down's syndrome and Alzheimer's disease: a light microscopical analysis. AB - The distribution and severity of the neuropathological changes in 57 cases of Alzheimer's disease, and 11 patients with Down's syndrome were investigated with reference to the cerebellum. A modified silver stain and a monoclonal antibody raised against amyloid beta-protein were used to identify amyloid plaques. The highest incidence of amyloid plaques in the cerebellum (93%) was found in the group of patients who developed dementia before 65 years of age. This figure dropped to 56% in those patients with dementia beginning after 75 years. In 37 of these cases the distribution of the pathological changes of the disease were also examined in the brain stem. The severity of the pathological changes in the cerebellum corresponded to the involvement of the brain stem nuclei with connections to the cerebellar cortex. The possibility that the disease process spreads to the cerebellum by involving the fibres from the brain stem is discussed with reference to previous anatomical and neurochemical studies. PMID- 8493863 TI - The topographic distribution of brain atrophy in Huntington's disease and progressive supranuclear palsy. AB - The topographic distribution of brain atrophy was quantified by image analysis of fixed coronal brain slices from 12 patients dying with Huntington's disease (HD) and from 4 other patients dying with progressive supranuclear palsy (PSP). In HD, atrophy was maximal within the caudate nucleus, putamen and globus pallidus. However, the cerebral cortex was also atrophied with reductions in cross sectional area within frontal, temporal and parietal lobes. In general, more white matter than grey matter was lost leading to an elevation in the grey/white matter ratio. The amygdala and thalamus were reduced in area. In PSP, lesser reductions in cortical area than those of HD were seen, these again being mostly due to a loss of white matter, resulting in an elevation of the grey/white ratio. The globus pallidus and thalamus were decreased in area, but no changes in the caudate nucleus and putamen were measured. PMID- 8493864 TI - Inflammatory cells in the peripheral nervous system in motor neuron disease. AB - We examined post-mortem material of the peripheral nervous system of 26 cases of motor neuron disease (MND) for the presence of lymphocyte subsets and macrophages. Findings were quantified and compared with those in control nerves. Lymphocytes in chronic and acute axonal degeneration were studied in sural nerve biopsy and animal material. Signs of demyelination were studied in MND and controls with infiltrates of T cells. A few T lymphocytes were scattered diffusely within the fascicles. The numbers did not differ between MND and controls. About half of the T cells was positive for CD45RA, the other half being positive for CD45RO. T cells were negative for CD25, CD54 and major histocompatibility complex (MHC)-class II. There were hardly any B lymphocytes. The numbers of lymphocytes in nerves with and without axonal degeneration did not differ. Increased MHC class II expression was present on denervated Schwann cells and macrophages in MND and in sural nerves with axonal degeneration. Macrophages were increased in number and in size, both in MND and in control material with axonal degeneration. No signs of demyelination were present either in MND or in controls. It is concluded that a T cell-mediated process in peripheral nerves in MND is very unlikely. PMID- 8493865 TI - Subacute panencephalitis associated with chronic graft-versus-host disease. AB - A unique form of subacute panencephalitis developed in a child with aplastic anemia 8 months after an allogeneic bone marrow transplantation (BMT). It was characterized by parenchymal infiltration of CD3 lymphocytes, a marked increase in the number of microglia strongly expressing HLA-DR antigens in both the gray and white matter, and diffuse degeneration of the cerebral white matter. The onset of neurological symptoms coincided with the development of chronic systemic graft-versus-host disease (GVHD). Cellular infiltrates in the CNS lesions were exclusively CD3 lymphocytes intermingled with a small number of monocytes labeled with CD68. There was a preponderance of cells of the CD45RB phenotype. The pathological changes in visceral organs were consistent with those of chronic GVHD. In addition, scrutiny of immunohistochemistry disclosed sparse infiltration of CD3 lymphocytes and diffuse gliosis in the cerebral white matter of another child with chronic GVHD who died 9 months after allogeneic BMT. These cases are suggestive of a potential risk of CNS involvement in GVHD. PMID- 8493866 TI - Infection after knee arthroplasty. Clinical studies of skin hypoxia and wound healing. PMID- 8493867 TI - Collagen synthesis of human arterial smooth muscle cells: effects of platelet derived growth factor, transforming growth factor-beta 1 and interleukin-1. AB - The effects of platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF-beta 1) and interleukin-1 (IL-1) on collagen synthesis of cultured human arterial smooth muscle cells in a confluent state were investigated. Synthetic activity of collagenous protein was determined with [3H]-proline uptake, and subsequent analysis of collagen types by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/mL) enhanced total collagen synthesis per dish, it suppressed total collagen synthesis per DNA (DNA content in a dish). TGF-beta 1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and per DNA. IL-1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesis both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densitometric analysis showed PDGF suppressed the proportion of type IV collagen and increased that of type V collagen. TGF-beta 1 increased the proportions of types IV and V collagen. IL-1 elicited un- remarkable change in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS-beta 1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism by stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen. PMID- 8493868 TI - Organ distribution of mutant mitochondrial tRNA(leu(UUR)) gene in a MELAS patient. AB - Point mutations in the mitochondrial tRNA(leu(UUR)) gene have been recently reported in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). To investigate the relationship between the degree of heteroplasmy and the organ damage, the ratio of mutant and wildtype genes was quantitated in 14 different organs obtained at an autopsy case of MELAS. The percentages of mitochondrial tRNA(leu(UUR)) gene carrying an A to G transition mutation at nucleotide 3243 were determined by the restriction enzyme digestion of the polymerase chain reaction products. The organs largely depending on oxidative phosphorylation for the sources of energy contained higher proportions of the mutant tRNA(leu(UUR)) gene than organs with a lower oxygen demand. However, the percentage of the mutant genes was similar in both symptomatic and asymptomatic organs with a higher oxygen demand. PMID- 8493869 TI - An unusual heterotopia of pyloric glands of the stomach with inverted downgrowth. AB - A rarely reported, large heterotopia of gastric glands in the submucosal layer of the stomach is observed in a 79 year old Japanese man with early gastric cancer. Histologically, it consists of marked hyperplasia of benign foveolar-type epithelia and tubular glands which instead of growing upwards grow downwards into the submucosa. Immunohistochemically, many gastrin-positive G cells are observed within it, indicating the existence of independent pyloric-type glands from the surrounding mucosa with intestinal metaplasia. Muscle actin-positive fascicles, derived from the muscularis mucosae, are demonstrated to branch into it and to encapsulate it. This result suggests that the present lesion may not represent a truly submucosal ectopic location, but an inverted downgrowth of the mucosa into the submucosa, thus resembling an inverted polyp of the colon. An awareness of this unique lesion is important in order that it not be mistaken for a submucosal extension of the primary adenocarcinoma. PMID- 8493870 TI - Malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve. AB - A case of a malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve in a 38 year old man is reported. At autopsy, the tumor was found to be extensively involved in the right cerebellopontine angle of the brain stem. Histologically, the tumor was composed mainly of spindle-shaped tumor cells proliferating in hypercellular fascicles scattered with pleomorphic cells. The tumor cells were characterized by high mitotic activity and invasive growth. Occasional tumor cells had eosinophilic cytoplasm, which in a few cases was cross-striated. Cytoplasmic interdigitations and a thick basal lamina were confirmed ultrastructurally. Immunohistochemical analysis revealed that some tumor cells were positive for myoglobin and desmin, but weakly positive or negative for S-100 protein. The patient did not have von Recklinghausen's disease. PMID- 8493871 TI - Alveolar soft part sarcoma of the uterine cervix. AB - A rare case of an alveolar soft part sarcoma of the uterine cervix in an 8 year old girl is presented. The patient was admitted because of genital bleeding lasting for 7 months. A polypoid tumor, 2 x 1.5 cm in diameter, was found in her external uterine os and was surgically resected. Microscopically, the tumor consisted of a uniform sheet of tumor cells in the cytoplasm which contained granules and which were stained with periodic acid-Schiff, both before and after the diastase digestion. Alveolar arrangement of the tumor cells was manifested with reticulin silver impregnation. Dense, membrane bound granules were evident at an ultrastructural level in the cytoplasm of the tumor cells. An immunohistochemical examination demonstrated a positive reaction for anti-desmin, anti-myoglobin, anti-HHF35 and anti-neuron specific enolase in the cytoplasm. PMID- 8493872 TI - Carcinosarcoma of the prostate. AB - A unique case of carcinosarcoma of the prostate occurring in a 32 year old man is presented. This is the youngest case reported to date among nine well-documented examples. The patient underwent a total prostatectomy under the diagnosis of prostatic sarcoma. Despite adjuvant chemotherapy and full-dose radiotherapy being undertaken, the patient died from multiple lung metastases about 8 months after the operation. The surgically resected primary tumor was composed of two histologically distinct elements, these being an undifferentiated carcinoma and a sarcoma with various mesodermal components. These elements were intimately intermingled and transitional forms were often noticed. The sarcomatous portion contained myxoid areas, spindle cell sarcomas with nuclear palisading, areas of osteoid formation and small islands of chondromatous differentiation. The pathogenesis of this complex neoplasm is discussed, and it is suggested that vestigial embryologic Mullerian mesodermal tissue may be capable of diverse differentiation. PMID- 8493873 TI - Age-related changes in force and efficiency in rat skeletal muscle. AB - We investigated the effect of age on (the reduction of) work output, efficiency and muscle fibre type composition. Rat medial gastrocnemius muscles of three age groups performed a series of 15 repeated contractions within 6 s (blood flow was arrested). Stimulation and shortening velocities were chosen as optimal for each group, while all muscles shortened over the same relative fibre lengths. The fibre type composition showed a higher proportion of the oxidative type IIBd fibres in the middle-aged group [5 months old; 39.8 +/- 6.8 vs. 23.6 +/- 4.2% of the fibre area in the young rats (1.3 months old)] in contrast to the type IIBm fibres (52.9 vs. 67.9%, respectively), while the old group (22 months old) was not different from the middle-aged group. Work output in the last contraction (relative to the first contraction) was not different between the age-groups (53.1 +/- 18.1; 48.0 +/- 6.5 and 61.1 +/- 6.2%, respectively). High-energy phosphate utilization was not different between the groups (150.6 +/- 11.2; 154.6 +/- 15.6 and 157.2 +/- 7.0 mumol g-1 dry wt, respectively). However, the efficiency was approximately 30% lower in the muscles of the youngest group, which corresponds with a lower specific power and specific tension. Since the change in fibre type composition is unlikely to be the cause of the low efficiency in the young animals, the causes remain unclear, but may be related to the rapid growth of the young rats in our study. PMID- 8493874 TI - Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes. AB - Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7-8 wk duration). Bladder wet wt was almost 4-fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to PO2 100 mmHg for both control and diabetic muscle strips. At zero PO2 force was reduced by approximately 10 20%, in both groups. High-K+ solution induced 'tonic' contractions that were slightly more inhibited by lowering PO2. At intermediate PO2 (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero PO2 no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a PO2 of 290 mmHg and related to the volume of smooth muscle. At zero PO2, lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero PO2. No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue samples was about 2-fold higher in the diabetic bladder muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8493875 TI - Differential projection of the sural nerve to early and late recruited human tibialis anterior motor units: change of recruitment gain. AB - The effect of a stimulation of the cutaneous sural nerve [three shocks, 2.5 x perception threshold (PT)] was studied on the tibialis anterior (TA) H-reflex and single voluntarily activated TA motor units using post-stimulus time histograms (PSTH). In both cases, when studying only the first recruited motor units, an inhibition with a delay of 10 ms, in relation to the monosynaptic latency of Ia afferents in the common peroneal nerve, was observed. This inhibition had a duration of 10-20 ms. The inhibition was evoked by low-threshold cutaneous fibres, since it could be seen at a stimulation strength close to the perception threshold. The central delay of the inhibition was calculated in two subjects to be 1.8 ms and 1.2 ms respectively. The TA motor units were characterized by their recruitment threshold and minimal firing frequency and the effect of the sural nerve stimulation was subsequently investigated. Early recruited low frequency motor units were found to be inhibited, whereas later recruited motor units with a higher minimal firing frequency were facilitated. Similarly small TA H-reflexes were inhibited, whereas large reflexes were facilitated. This difference in the effect of the sural nerve stimulation was not caused by a difference in the descending command, since the same early recruited motor unit was still inhibited when firing at a high frequency and at a high torque level. Stimulation of the femoral nerve was found to produce a monosynaptic facilitation of the TA H-reflex and a heteronymous monosynaptic peak in the PSTH of single motor units. A stimulation of the sural nerve increased the size of the reflex facilitation, but had no effect on the size of the monosynaptic peak in the PSTH of the single motor units. It is concluded that the effect of the sural nerve stimulation on human TA motor units is similar to observations in the cat and that a similar interneuronal system may be responsible. It is furthermore suggested that the sural nerve stimulation increases the recruitment gain of the TA motoneuronal pool. PMID- 8493876 TI - Vasomotor response of the human face: laser-Doppler measurements during mild hypo and hyperthermia. AB - The skin of the face is reputed not to vasoconstrict in response to cold stress because the face skin temperature remains steady during hypothermia. The purpose of the present work was to measure the vasomotor response of the human face to whole-body hypothermia, and to compare it with hyperthermia. Six male subjects were immersed in cold and in warm water to obtain the two conditions. Skin blood flow, evaporation, and skin temperature (Tsk) were recorded in three loci of the face, the forehead, the infra orbital area, and the cheek. Tympanic (Tty) and oesophageal (Toes) temperatures were also recorded during the different thermal states. Normothermic measurements served as control. Blood flow was recorded with a laser-Doppler flowmeter, evaporation measured with an evaporimeter. Face Tsk remained stable between normo-, hypo-, and hyperthermia. Facial blood flow, however, did not follow the same pattern. The facial blood flow remained at minimal vasoconstricted level when the subjects' condition was changed from normo to hypothermia. When the condition changed from hypo- to hyperthermia a 3 to 9 fold increase in the blood flow was recorded. From these results it was concluded that a vasoconstriction seems to be the general vasomotor state in the face during normothermia. PMID- 8493877 TI - Sympathetic baroreflex control of vascular resistance in comfortably warm man. Analyses of neurogenic constrictor responses in the resting forearm and in its separate skeletal muscle and skin tissue compartments. AB - Resting forearm vascular resistance changes elicited in male volunteers by graded reflex sympathetic activation evoked by graded lower body negative pressure (LBNP) were studied at room temperatures of 24-25 and 20-21 degrees C. The latter condition caused strong suppression of skin flow and permitted preferential analysis of muscle responses and, by comparison with responses at 24-25 degrees C, secondary estimation of circulatory reactions in the skin. Short-lasting LBNP bouts (1.5 min) allowed analyses of reflex vascular reactions to high and barely tolerated LBNP (85 mmHg) and thereby to high levels of circulatory stress and sympathetic nerve discharge, yet without risks for the subjects under study. Both muscle and skin reacted intensely and in a graded manner to graded sympathetic activation with very pronounced resistance change (74-77% flow decline; 350-400% resistance rise above control level) at high LBNP. Therefore, the sympathetic vasomotor fibres can exert a very potent control of vascular resistance both in skeletal muscle and in skin under thermoneutral conditions, and both tissues apparently can serve as major targets for powerful sympathetic homeostatic baroreflexes. Evidence indicated that this control is exerted from both low pressure cardiopulmonary and high-pressure arterial baroreceptor areas. These conclusions deviate from previous literature, in which baroreflex sympathetic vasoconstriction in the human limb has been proposed to be more or less selectively mediated from cardiopulmonary receptors and, further, muscle to respond fully already at mild circulatory stress without further constriction if the stimulus is increased. PMID- 8493878 TI - Lactation affects pressor, volumetric and natriuretic responses to angiotensin II in goats. AB - Demands on cardiovascular function and fluid turnover increase during lactation and pregnancy in the goat, but the hormonal status is different. This study is aimed at investigating the effects of hypertensive angiotensin II (ANGII) in lactating goats. The results were compared with those of pregnancy and control conditions. ANGII (0.5 microgram min-1) was infused intravenously for 60 min (n = 6). The rise in blood pressure in response to ANGII was attenuated during lactation as in pregnancy (P < 0.001 vs control period). ANGII caused reflex bradycardia. Plasma protein concentration decreased by 7.5% during infusions in lactating goats (pregnancy: 9%; control period: 4.5%). Renal Na excretion increased by 260% (lactation), by 400% (pregnancy; n.s. vs. lactation), and by 800% (control period; P < 0.01 vs. lactation). The glomerular filtration rate was unchanged during ANGII infusions in lactating animals, but increased in the other periods. Effective renal plasma flow decreased. ANGII raised aldosterone from < 34.5 pmol l-1 to 539 +/- 80 pmol l-1 (lactation) and to 428 +/- 41 pmol l-1 (control; P < 0.05 vs. lactation), and from 72 +/- 9 to 651 +/- 103 pmol l-1 (pregnancy; P < 0.01 vs. lactation). Plasma progesterone was undetectable during lactation, but varied from 0 to 17 nmol l-1 during control conditions and was 16 +/- 1 nmol l-1 during pregnancy. Oestradiol 17 beta was 181 +/- 22 pmol l-1 in pregnant goats, and undetectable in lactating animals. In conclusion, lactation affects ANGII-induced changes in cardiovascular and fluid regulation, but in this period the effects were not related to progesterone or oestradiol 17 beta. PMID- 8493879 TI - Intermittent salt-loading for 10 days causes a temporary drop in amidating processing enzyme activity but a persistent drop in arginine-vasopressin in the rat neurohypophysis. PMID- 8493880 TI - Presynaptic regulation of hippocampal acetylcholine release is unaffected by calcium channel blockers and intracellular calcium chelation. PMID- 8493881 TI - Percutaneous gallbladder and urinary bladder rotational lithotripsy and a model for gallbladder sclerotherapy after lithotripsy. Clinical and experimental studies. AB - In experiments in pigs, fragmentation of stones implanted into the gallbladder and the urinary bladder, respectively, was successfully achieved by mechanical rotational lithotripsy with the Rotolith lithotriptor. The stones could be fragmented into pieces about 1 mm in diameter. Ten patients were selected for percutaneous rotational lithotripsy of gallbladder stones. The procedure was completed in 7 of these 10 patients. Employing a suprapubic approach, the instrument was also used for lithotripsy of urinary bladder stones in 6 male patients. Percutaneous rotational lithotripsy is well suited for elderly patients with symptomatic gallbladder stones and concurrent disease making them high-risk patients for surgery and general anesthesia. Fragmentation of urinary bladder stones in the clinical setting was not as successful as in our experimental series, probably due to the larger volume of the human urinary bladder and the high specific weight of the bladder stones. The feasibility of rotational lithotripsy of urinary bladder stones is conceivable, but when compared with current methods, the use of the Rotolith lithotriptor did not yield any advantage. Ablation of the gallbladder is of great interest to prevent recurrence of cholecystolithiasis after lithotripsy. Rotational lithotripsy of gallbladder stones was performed in an experimental model in 42 pigs to study chemical and thermal sclerotherapy with various agents in edematous gallbladders. A total ablation of the gallbladder mucosa was difficult to effect. Remnants of mucus producing epithelium persisted in a high percentage of the histologic specimens. Sclerotherapy cannot be considered an effective method for "nonsurgical cholecystectomy." PMID- 8493882 TI - MR imaging in cerebral gliomas analysis of tumour tissue components. AB - The aim of this investigation was to assess the capacity of MR imaging to identify the tumour components of cerebral gliomas and thus to grade and delineate these tumours. A comparative analysis between MR examinations and histopathologic whole-brain sections was performed in 5 brain specimens from patients with malignant glial tumours. All cases were examined with MR imaging in vitro. In 2 cases a close comparison with the MR examination in vivo was also possible. The homogeneous hypercellular tumour core was not an isolated entity with typical signal characteristics in any sequence used. However, the tumour core was better observed in T2WI than in T1WI or PDWI, its signal characteristics both in vitro and in vivo being more hypointense than the peritumoural oedema. The use of image subtraction and T2 maps in combination with T2WI increased our capacity to correctly distinguish the most malignant part, compared with using each of these methods separately. In all cases, benign-looking tumour cells were found in the most peripheral aspects of the peritumoural oedema. These cells were not separately identified by any MR sequence or MR imaging method used. In 4 of the 5 cases of malignant glial tumours, we found isolated tumour cells and even larger tumour cell areas, though consisting of benign-looking cells, in areas that were visualized as normal in all sequences and MR imaging methods used. In all cases the necroses were heterogeneous. This heterogeneity was best reflected in the T2WI. Necroses were the most conspicuous tumour components in cases of malignant glioma and best reflected the underlying heterogeneous histopathology. A comparison between contrast-enhanced CT, Gd-DTPA-enhanced MR imaging and positron emission tomography (PET) with 11C-L-methionine was performed in 14 patients. In all patients except one, the area of increased 11C-L-methionine accumulation on PET, indicating viable tumour tissue, was the same size as, or larger than the extension of the contrast enhancement on both CT and MR. Contrast enhanced MR and CT gave similar results as regards tumour extension. The increase in signal intensity 5 min post-contrast tended to be greater in the high-grade than in the low-grade tumour group. In order to evaluate the short- and long-term effects of formalin fixation on T1 and T2 of cerebral grey and white matter, MR imaging was also performed in 5 whole-brain specimens from patients with no known brain disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8493883 TI - Influence of intracellular pH on light emission from a luxA/B derivative of Lactococcus lactis subsp. diacetylactis. AB - High levels of constitutive aldehyde-dependent light emission were obtained from nongrowing cells of Lactococcus lactis subsp. diacetylactis F712 transformed with IuxA/B when they were suspended in buffered solutions. Inductions of light emission was time-dependent and was not due to growth, synthesis of luciferase or stimulation of metabolism by fermentable carbohydrate. The major factor controlling light emission in such cells appears to be the intracellular pH value. Experiments with ionophores indicated that a transmembrane pH gradient was not essential for light emission. PMID- 8493884 TI - Application of in vivo bioluminescence to the study of ionophoretic action. AB - Ionophores (carbonyl cyanide m-chlorophenylhydrazone; valinomycin; and the hop derived compounds colupulone, trans-isohumulone and trans-humulinic acid) reduced the rate of dodecanal-dependent light emission from IuxA/B-transformed cells of Lactococcus lactis subsp. diacetylactis F712 when the cells were suspended in a buffered medium (pH 6.4) containing glucose. This allowed an assay for ionophores to be devised and permitted measurement of the effects of such compounds on the test organism by the use of a non-destructive technique in real time. PMID- 8493885 TI - Effect of adherence to plastic on peripheral blood monocyte and alveolar macrophage chemiluminescence. AB - The chemiluminescence of peripheral blood monocytes and alveolar macrophages was determined in the presence of luminol and lucigenin, either before or after the cell adherence to the luminometer curvettes. In the case of monocytes, cell adherence induces an increase of luminol-dependent chemiluminescence and has almost no effect on the lucigenin-dependent chemiluminescence. However, it shows a strong inhibition of the lucigenin-dependent chemiluminescence and almost no effect on luminol-dependent chemiluminescence, in the case of alveolar macrophages. These results show that adhesion to plastic alters the metabolic burst of both monocytes and alveolar macrophages. Although the mechanisms are poorly understood, they seem to be related to the modifications that take place during the differentiation of peripheral monocytes to alveolar macrophages. PMID- 8493886 TI - Chemiluminescence of mononuclear cells is enhanced during antigen recognition. AB - Stimulation of phagocytes by several cytokines causes superoxide generation and consequently chemiluminescence. Since antigen-activated lymphocytes generate cytokines, we investigated whether antigen recognition by mononuclear cells, which contain both lymphocytes and monocytes, is accompanied by changes in lucigenin-dependent chemiluminescence. Mononuclear cells which underwent antigen induced proliferation showed a delayed rise in lucigenin-dependent chemiluminescence in the absence of other stimuli. The common recall antigen Candida albicans increased spontaneous chemiluminescence of mononuclear cells from unselected donors up to 20-fold over control values after 48-72 h of culture. With Rabies virus vaccine as specific antigenic stimulus, only mononuclear cells from rabies immunized individuals responded with enhanced delayed chemiluminescence. In contrast to opsonized zymosan and phorbol myristate acetate, antigens induced no oxidative burst within one hour after addition. Delayed mononuclear cell chemiluminescence was inhibited by the superoxide scavenger superoxide dismutase and by di-phenylene iodonium, a selective inhibitor of the phagocyte NADPH oxidase. A neutralizing monoclonal antibody against interferon-gamma completely abrogated antigen-induced chemiluminescence. Recombinant interferon-gamma by itself induced delayed mononuclear cell chemiluminescence. Thus, antigen-induced delayed mononuclear cell chemiluminescence represents activation of phagocyte NADPH oxidase by interferon gamma generated by activated lymphocytes. PMID- 8493887 TI - Bioluminescence and chemiluminescence literature. The 1992 literature: Part I. PMID- 8493888 TI - The efferent system of cranial nerve nuclei: a comparative neuromorphological study. AB - A number of inconsistencies and controversies are inherent in the classification of cranial nerve nuclei based on the concepts of the various head-theories. The assumption of head segmentation, which is common to these theories, serves as the basis for designating the dorsomedial nuclei as the somatomotor column, although they innervate striated muscles of a viscus and a specific sense organ. The ventrolateral nuclei are called the specific visceromotor column; they innervate striated muscles in the branchiogenous area, but many of these muscles insert on skeletal elements. A series of comparative neuromorphological studies investigating the dendritic arborization pattern and axonal trajectory in the frog, lizard, and rat suggests a much more delicate classification in which nine morphologically and functionally different neuron groups can be discerned: 1. The hypoglossal nucleus appears coincidentally with the muscular tongue in amphibia. The spindle-shaped perikaryon, the bipolar dendritic arborization, and the straight ventral trajectory of the axon are characteristic morphological features in all three animal species investigated. 2. The oculomotor, trochlear, and abducens nuclei present a remarkably conservative topography and organization in all vertebrates with a moving eye. With their oval-shaped or polygonal perikarya and radiating dendritic arborization, these neurons distinctly differ from hypoglossal neurons. The ipsilateral axons follow a straight ventral course, the contralateral axons form a dorsal loop before crossing the midline, and the crossing is not consequence of neuron migration to the contralateral side. 3. The accessory abducens nucleus is present in tetrapods except apes and human. The elongated perikaryon and the dorsoventral dendritic orientation distinctly distinguish these neurons from other cranial motoneurons, the nucleus is found in the lateral part of the reticular formation. The neurons differentiate in situ, they do not migrate from the main abducens nucleus. 4. In the submammalian trigeminal and facial nuclei, two basic neuron types can be distinguished on the basis of their morphology. The first type is larger and accumulates in the rostral part of the trigeminal nucleus. This type innervates the jaw closer muscles. The second type is found in the caudal part of the trigeminal nucleus and in the facial nucleus. These neurons innervate the muscular floor of the mouth and the facial contingent supplies the jaw opener muscle. A very characteristic feature in the axonal trajectory is an initial medial course and a hairpin turn, or dorsal loop, at the lateral aspect of the medial longitudinal fasciculus. In addition to the two types of neurons, there is a third type in the frog trigeminal nucleus. This innervates an orbital muscle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8493889 TI - Tumor-associated aldehyde dehydrogenase (ALDH3): expression in different human tumor cell lines with and without treatment with 3-methylcholanthrene. PMID- 8493890 TI - Sexual differentiation in the induction of the class 3 aldehyde dehydrogenase. PMID- 8493891 TI - Mouse class 3 aldehyde dehydrogenases: positive and negative regulation of gene expression. PMID- 8493892 TI - Human stomach aldehyde dehydrogenase, ALDH3. PMID- 8493893 TI - Bovine corneal aldehyde dehydrogenases: evidence for multiple gene products (ALDH3 and ALDHX). PMID- 8493894 TI - Carbonyl-metabolizing enzymes and their relatives recruited as structural proteins in the eye lens. AB - The refractive properties of the eye lens are determined by abundant soluble structural proteins known as crystallins. While some crystallins are common to most vertebrates, others are abundant only in groups of related species. These taxon-specific crystallins all turn out to be enzymes, apparently recruited by modification of gene expression without prior gene duplication. They include eta crystallin, accounting for up to 25% of protein in elephant shrew lenses and apparently identical to cytoplasmic aldehyde dehydrogenase; rho-crystallin from frog lenses, a member of the same superfamily as aldose and aldehyde reductases; and zeta-crystallin, found in guinea pig and camel lenses, which is structurally related to alcohol dehydrogenase (ADH). Unlike ADH, zeta-crystallin requires NADPH rather than NAD+/NADH as cofactor. Molecular modelling of zeta-crystallin shows that amino-acid changes around the co-factor binding site are responsible for this change in affinity. Purified guinea pig lens zeta-crystallin has a substrate preference for orthoquinones which are reduced by a single electron transfer mechanism. cDNA sequencing of zeta-crystallin suggests that the expression in lens as a crystallin depends on a different gene promoter from that used predominantly in liver. The putative guinea pig zeta-crystallin lens promoter has now been assayed for function in transfection studies. Elements with positive and negative effects on transcription, at least one of which has tissue preferred function, have been defined. When introduced into transgenic mice this promoter exhibits tissue-specific expression in the lens. This is the first identification of a lens-specific, alternative promoter in an enzyme crystallin gene. PMID- 8493895 TI - Members of the ALDH gene family are lens and corneal crystallins. AB - Many of the major lens proteins, known as crystallins, responsible for the structural integrity and functional utility of this visual tissue have been previously shown to be recruited proteins. This phenomena of a protein that is expressed and functions elsewhere acquiring a new function in another tissue has been termed 'gene sharing'. It is now becoming obvious that the cornea of vertebrates has similarly acquired proteins, and that at least one corneal protein, ALDH3 belongs to a gene family that has been previously identified as a lens crystallin. The recognition that both lens and corneal crystallins exist is a novel concept that has implications that involve the process by which multifunctional gene products have evolved. Members of the ALDH gene family function in both the cornea and lens as crystallins and the acquisition of multifunctionality by this gene family is unique. Based on our analysis we have deduced a supragene family relationship between the thiol protein esterases, aldehyde dehydrogenases, and the taxon-specific crystallins. Evolution of a complex organ such as the vertebrate eye is not a sequential and gradual process such as the Darwinian Giraffe's neck, since the eye can provide selective advantage only as a complete organ. Catastrophic theory proposes that the complex vertebrate eye with its lens, and focussing mechanism arose from the primitive eye spot which contained originally only the photoreceptor system by a one step event. In the evolution of the vertebrate eye it is evolutionarily plausible that several pre-existing proteins have been recruited to perform a structural role for this complex organ. It is also incumbent in evolutionary thought that any inherent enzymatic activity associated with this protein would be purely an incidental addition to the organ. However, the fact that most of these have pyridine nucleotide binding capacity, which is presumed important in giving protection from UV exposure, is noteworthy. Finally, to construct the vertebrate eye in one step from the existing visual pigment system such as the eyespot of unicellular organisms the following criteria would apparently be advantageous: (1) high water solubility; (2) transparency; and (3) common genetic regulatory elements (e.g. promoters/enhancers). Although it is an important observation that certain members of the aldehyde dehydrogenase gene family are present as structural proteins in the cornea and lens, it is not surprising that the phenomenon of gene sharing extends to another ocular tissue such as the cornea. In this context, it will be interesting to note if similar multifunctional gene products will be found as frequently in organs other than the eye. PMID- 8493896 TI - Effects of aldehyde products of lipid peroxidation on the activity of aldehyde metabolizing enzymes in hepatomas. PMID- 8493897 TI - Retinoic acid synthesis in the developing retina. PMID- 8493898 TI - Human liver high Km aldehyde dehydrogenase (ALDH4): properties and structural relationship to the glutamic gamma-semialdehyde dehydrogenase. PMID- 8493899 TI - Photoaffinity labeling of aldehyde dehydrogenase from horse liver by P1-N6-(4 azidophenylethyl)adenosine-P2-[4-(3-azidopyridinio)butyl] diphosphate. PMID- 8493900 TI - Crystallization and preliminary X-ray analysis of bovine mitochondrial aldehyde dehydrogenase and human glutathione-dependent formaldehyde dehydrogenase. PMID- 8493901 TI - The aldo-keto reductases: an overview. PMID- 8493902 TI - Location of an essential arginine residue in the primary structure of pig aldose reductase. PMID- 8493903 TI - Cys298 is responsible for reversible thiol-induced variation in aldose reductase activity. PMID- 8493904 TI - Metabolic interactions of 4-hydroxynonenal, acetaldehyde and glutathione in isolated liver mitochondria. PMID- 8493905 TI - Substrate specificity of reduced and oxidized forms of human aldose reductase. PMID- 8493906 TI - Kinetic alteration of human aldose reductase by mutagenesis of cysteine residues. PMID- 8493907 TI - Inhibition of aldose reductase by (2,6-dimethylphenylsulphonyl)nitromethane: possible implications for the nature of an inhibitor binding site and a cause of biphasic kinetics. AB - Aldose reductase (aldehyde reductase 2, ALR2) is often isolated as a mixture of two forms which are sensitive (ALR2S), or insensitive (ALR2I), to inhibitors. We show that ICI 215918 ((2-6-dimethylphenylsulphonyl)-nitromethane) follows either noncompetitive, or uncompetitive kinetics with respect to aldehyde for ALR2S, or the closely related enzyme, aldehyde reductase (aldehyde reductase 1, ALR1). Similar behaviour is exhibited by two other structural types of aldose reductase inhibitor (ARI), spirohydantoins and acetic acids, when either aldehyde, or NADPH is varied. For ALR2S, we have demonstrated kinetic competition between a sulphonylnitromethane, an acetic acid and a spirohydantoin. Thus, different ARIs probably have overlapping binding sites. Published studies imply that ALR2 follows an ordered mechanism where coenzyme binds first and induces a reversible conformation change (E.NADPH-->E*.NADPH). Reduction of aldehyde appears rate limited by the step E*.NADP+-->E.NADP+. Spontaneous activation converts ALR2S into ALR2I and increases kcat. This must be associated with acceleration of the rate-determining step. We now propose the following hypothesis to explain characteristics of ARIs. (1) Inhibitors preferentially bind to the E* conformation. (2) The ARI binding site contains residues in common with that for aldehyde substrates. When aldehyde is varied, uncompetitive inhibition arises from association at the site for alcohol product in the E*.NADP+ complex which has little affinity for the substrate. Any competitive inhibition arises from use of the aldehyde site in the E*.NADPH complex. (3) Acceleration of the E*.NADP+- >E.NADP+ step upon activation of ALR2 reduces steady state levels of E* and so decreases sensitivity to ARIs. PMID- 8493908 TI - Sepiapterin reductase and ALR2 ("aldose reductase") from bovine brain. PMID- 8493909 TI - Polymorphisms of the aldose reductase locus (ALR2) and susceptibility to diabetic microvascular complications. PMID- 8493910 TI - Polycyclic aromatic hydrocarbons and phenolic antioxidants do not significantly induce carbonyl reductase in human cell lines. PMID- 8493911 TI - The purification and properties of a novel carbonyl reducing enzyme from mouse liver microsomes. PMID- 8493912 TI - Properties and stereoselectivity of carbonyl reductases involved in the ketone reduction of warfarin and analogues. PMID- 8493913 TI - Activation of pulmonary carbonyl reductase by aromatic amines and pyridine ring containing compounds. PMID- 8493914 TI - Biological role of human cytosolic aldehyde dehydrogenase 1: hormonal response, retinal oxidation and implication in testicular feminization. PMID- 8493915 TI - Unique dihydrodiol specific dehydrogenase of bovine liver: inhibition studies and comparison with aldo/keto reductase. PMID- 8493916 TI - Carbonyl reduction by 3 alpha-HSD from Comamonas testosteroni--new properties and its relationship to the SCAD family. PMID- 8493917 TI - Substrate specificity of alcohol dehydrogenases. PMID- 8493918 TI - The influence of pH on the substrate specificity and stereoselectivity of alcohol dehydrogenase from horse liver. PMID- 8493919 TI - The catalytic specificity of liver alcohol dehydrogenase: vitamin A alcohol and vitamin A aldehyde activities. PMID- 8493920 TI - A synthetic approach to analysis of the structural zinc site of alcohol dehydrogenase. PMID- 8493921 TI - Site-directed mutagenesis of mammalian alcohol and sorbitol dehydrogenases map functional differences within the enzyme family. PMID- 8493922 TI - Human cytosolic aldehyde dehydrogenase in androgen insensitivity syndrome. PMID- 8493923 TI - Horse liver alcohol dehydrogenase-S-isozyme: confirmation of the primary structure by protein sequencing and ion spray mass spectrometry. PMID- 8493924 TI - Mixed substrate experiments with class III (chi) alcohol dehydrogenases from human and pig liver and stomach. PMID- 8493925 TI - Glutathione-dependent formaldehyde dehydrogenase/class III alcohol dehydrogenase: further characterization of the rat liver enzyme. PMID- 8493926 TI - Class IV alcohol dehydrogenase: structure and function. PMID- 8493927 TI - The oxidation of aldehydes by horse liver alcohol dehydrogenase. AB - A lag phase in the spectrophotometric assay progress curve of aldehyde oxidation by HL-ADH was observed and characterised. The aldehyde oxidation and aldehyde dismutation reactions were shown to be related, and a mechanism to explain net aldehyde oxidation was proposed. The spectrophotometric assay was shown to be unsuitable for measurement of kinetic parameters for aldehyde oxidation by HL ADH, and kinetic constants previously determined were shown to be in error. Existing data on the aldehyde dismutation reaction are insufficient to discount a role for HL-ADH in aldehyde transformation in vivo. PMID- 8493928 TI - Effect of glycation upon activity of liver alcohol dehydrogenase. PMID- 8493929 TI - Metabolic role of aldehyde dehydrogenase. PMID- 8493930 TI - The use of immortalized mouse L1210/OAP cells established in culture to study the major class 1 aldehyde dehydrogenase-catalyzed oxidation of aldehydes in intact cells. PMID- 8493931 TI - Fluorescence studies of ternary complexes of liver alcohol dehydrogenase. PMID- 8493932 TI - Evolutionary relationships of branched chain and nonspecific alcohol and aldehyde dehydrogenases. PMID- 8493933 TI - Enzyme and isozyme developments within the medium-chain alcohol dehydrogenase family. PMID- 8493934 TI - Tissue distribution of alcohol and sorbitol dehydrogenase mRNAs. PMID- 8493935 TI - The role of alcohol and aldehyde dehydrogenases in alcohol-related diseases: clinical studies of molecular markers. PMID- 8493936 TI - Regulation of the human alcohol dehydrogenases genes ADH1, ADH2 and ADH3: differences in cis-acting sequences at CTF/NF-I sites. PMID- 8493937 TI - Modulation of hepatic and renal alcohol dehydrogenase activity and mRNA by steroid hormones in vivo. PMID- 8493938 TI - Alcohol- and aldehyde-dehydrogenase: modulation by biogenic amine metabolites, neuropeptides and psychoactive agents. AB - The results suggest the feasibility of metabolic and behavioral interrelationships between ethanol (ET), certain neurotransmitter substances and major metabolites, some neuropeptides and/or psychoactive agents. This was indicated by the in vivo and in vitro effects of such authentic compounds on certain ET-elicited behavioral responses and on hepatic ET and acetaldehyde metabolizing enzymes in rats and mice. PMID- 8493939 TI - Microbial alcohol, aldehyde and formate ester oxidoreductases. PMID- 8493940 TI - Carbonyl metabolising enzymes in alkane-grown microorganisms. PMID- 8493941 TI - Enhanced transcription of the cytosolic ALDH gene in cyclophosphamide resistant human carcinoma cells. PMID- 8493942 TI - Attempts to increase the expression of rat liver mitochondrial aldehyde dehydrogenase in E. coli by altering the mRNA. PMID- 8493943 TI - Preliminary characterization of the rat class 3 aldehyde dehydrogenase gene. PMID- 8493944 TI - Human high-Km aldehyde dehydrogenase (ALDH3): molecular, kinetic and structural features. PMID- 8493945 TI - Overexpression or polycyclic aromatic hydrocarbon-mediated induction of an apparently novel class 3 aldehyde dehydrogenase in human breast adenocarcinoma cells and its relationship to oxazaphosphorine-specific acquired resistance. PMID- 8493947 TI - Unpredictability of commercially available exoantigen culture confirmation tests in confirming the identity of five Blastomyces dermatitidis isolates. AB - Colonial and microscopic features of five fungal isolates from three patients suggested Blastomyces dermatitidis. Extracts from the mold forms of all isolates were tested on several occasions with commercially available Exoantigen immunodiffusion culture-confirmation test reagents and Nolan reagents. All three isolates from patient 1 were negative on four separate attempts with Exoantigen reagents using conventional ("slant") and "broth" extraction methods, and were also negative on one attempt with the Nolan reagents. The isolate from patient 3 was negative on three attempts using both reagent kits. The isolate from patient 2 was negative on four of five attempts with Exoantigen test reagents and positive on one attempt with Nolan reagents. Commercially prepared chemiluminescence-labeled DNA probes (Gen-Probe, San Diego, CA) directed at ribosomal RNA from B. dermatitidis and Histoplasma capsulatum confirmed all five isolates as B. dermatitidis. The cost and labor of the exoantigen and DNA Probe culture confirmation tests were evaluated. New methods for confirming the identity of cultural isolates of B. dermatitidis that are sensitive, specific, and commercially available are greatly needed. PMID- 8493946 TI - The effect of skin disinfection materials on reducing blood culture contamination. AB - Contaminated blood cultures may cause results to be misinterpreted, create unnecessary work for the laboratory, and increase costs. Disinfection of the venipuncture site is considered to be necessary for preventing contamination, although there is little information about the effectiveness of using different disinfection materials. The use of 70% isopropyl pads and povidone iodine saturated swabs (conventional method) was compared with the use of a 70% isopropyl/10% acetone scrub and povidone iodine dispenser (PREP method) for skin disinfection. Blood culture "kits" were prepared--bags containing collection tubes, instructions, and either conventional or PREP materials and were distributed randomly. The contents were concealed by a cover to prevent the user from selecting a specific type of decontamination kit. The kits were identified in the laboratory by color-coded labels on the collection tubes. Among 1,546 specimens evaluated, the contamination rate observed with conventional disinfection was significantly higher (4.6%; N = 763) than with PREP materials (2.2%; N = 783, P = 0.011) and was equivalent to the preceding 6-month contamination rate (4.7%). The lower contamination rate may be associated with greater effectiveness of a scrub or isopropyl/acetone solution, or both. Decontamination materials may have a significant impact on reducing blood culture contaminants from skin flora. PMID- 8493948 TI - A review of the clinical indications for the plasma heparin assay. AB - The basis for the clinical indications for the use of the plasma heparin assay for anticoagulation control are reviewed, and alternatives for currently used laboratory methods of monitoring heparin therapy in selected clinical situations are recommended. Many literature references support the role of plasma heparin assay with combined heparin and warfarin therapy, with combined heparin and recombinant tissue plasminogen activator therapy, in situations in which heparin resistance is noticed in the presence of a circulating anticoagulant, and in patients receiving heparin in an unrecognized manner, as well as with the use of the low molecular weight heparins. For now, however, in the absence of any prospective clinical trials establishing the superiority of the plasma heparin assay compared with the APTT, the recommendations outlined are presented as guidelines for the more specific monitoring of heparin therapy using currently available techniques. PMID- 8493949 TI - Nuclear DNA content, proliferation index, and nuclear size determination in normal and cirrhotic liver, and in benign and malignant primary and metastatic hepatic tumors. AB - The distribution values of ploidy, of the proliferation index, of the percentages of diploid cells/case, of nuclear size, and DNA histogram type are described in a series of 92 liver samples from 87 patients. The 92 samples include normal (31 cases) and cirrhotic (14 cases) tissues, benign tumors (7 cases), well differentiated hepatocellular carcinomas (HCCs, 13 cases), moderately and poorly differentiated HCCs (8 cases), and colorectal glandular metastatic tissues (19 cases). The samples are from either fine-needle aspiration biopsy (FNAB) or histologic imprint smears (HIS). Nuclear assessments were computed on Feulgen stained nuclei by means of a cell image processor. The results show that the mean DNA index value, the mean nuclear area (NA) value, and the mean percentages of diploid cells per sample are significantly different in the three benign groups under study (normal and cirrhotic tissues and benign tumors) as compared with the mean parameter values from the three neoplastic liver groups (well-differentiated and poorly differentiated HCCs and colorectal metastases). None of these three parameters, however, makes it possible to discriminate clearly between these six histopathologic groups at the individual case level. The mean proliferation index values were significantly lower in the normal tissues and the benign tumors than in the four other histopathologic groups. Recognizing six DNA histogram types, ie, diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic, we observed that all the benign samples (the normal and cirrhotic tissues and the benign tumors) exhibited a diploid and/or tetraploid DNA histogram pattern, whereas the neoplastic samples exhibited the six DNA histogram patterns. The combination of the five computerized parameters into a cytologic score (CS) ranging from 5 to 15 permits clear-cut discrimination between nonneoplastic and neoplastic liver cases. The specificity and sensitivity, and the positive and negative predictive values relating to this score were as high as 100%, 95%, 100%, and 96%, respectively. PMID- 8493950 TI - Computerized interactive morphometry and the diagnosis of lymphoid-rich effusions. AB - An experimental computerized interactive morphometry system for the classification of lymphoid-rich effusions is presented. The relatively inexpensive microcomputer-based system was assembled in our laboratory with commercially available hardware and software. One hundred twenty-two effusions (86 benign lymphocytoses, 26 lymphomas, and 10 chronic lymphocytic leukemias) were studied. Lymphoid cells were selected randomly by the system from real-time images of Papanicolaou-fixed and stained cytospin smears of pleural, peritoneal, and pericardial effusions. Parameters of nuclear shape, area, and optical density were measured automatically. Multiparameter statistical procedures of discriminant classificatory analysis analyzed the distribution of lymphoid nuclear profile integrated optical density to yield three groups of effusions, each with a predictive value of diagnosis of 100%. Neither these statistical procedures nor a simple rule-based expert system accurately classified chronic lymphocytic leukemia effusions based on the distribution of lymphoid nuclear profile area. When chronic lymphocytic leukemia effusions were excluded, however, the predictive values of a diagnosis of lymphoma by statistical analysis and by rule-based expert system were 92.3% and 88.9%, respectively, whereas the predictive values of a diagnosis of benign lymphocytosis were 97.7% and 91.3%, respectively. Potential applications and limitations of this technology for the diagnosis of lymphoid-rich effusions are discussed. PMID- 8493951 TI - The success of a clinical librarian program in an academic autopsy pathology service. AB - Residents in pathology must acquire a broad base of knowledge in all areas of medicine and the basic medical sciences. We report our experience with the first Clinical Medical Librarian (CL) program used to aid resident training in anatomic pathology. This program was developed by the Lister Hill Library of Health Sciences (LHL) of the University of Alabama at Birmingham (UAB) to test the value of a CL program in filling the clinical needs of medical students and residents by providing key recent references to the wide variety of diseases seen in a busy autopsy service. Use of a CL was accepted completely by both faculty and residents as a method of increasing their efficiency in evaluating the recent literature on diseases seen in the autopsy service. Our use of this program broadened the scope and extent of specific case-oriented medical literature read by both residents and faculty. PMID- 8493952 TI - Fine-needle aspiration biopsy of pulmonary coccidiodomycosis. Spectrum of cytologic findings in 73 patients. AB - Coccidioides immitis, the causal agent of coccidiodomycosis, is endemic in the arid desert regions of Mexico and the southwestern United States. Individuals may acquire the disease through the inhalation of conidia. The majority of infected patients are asymptomatic or exhibit flu-like symptoms. Two percent of infected individuals ultimately demonstrate a solitary pulmonary nodule that may be radiographically indistinguishable from neoplasms or other infectious lesions. This report describes the spectrum of cytologic findings in 73 patients who were diagnosed with pulmonary coccidiodomycosis by fine-needle aspiration (FNA) biopsy. The patients ranged in age from 30 to 92 years. Ten had a previous history of malignancy. The smears were characterized by a large amount of granular, eosinophilic debris with a paucity of acute or chronic inflammation. Granulomatous inflammation was present in only three cases. The diagnosis was confirmed by the cytologic observation of C. immitis spherules that ranged in size from approximately 20 to 200 microns. Many of these spherules had a crushed or fractured appearance, and occasional calcified forms were seen. Endospores were observed in intact spherules and were rarely observed outside these spherules. Mycelial elements occasionally were present. C. immitis were cultured in 9 of 44 cases in which fungal cultures were obtained. The cytologic differential diagnosis, which includes contaminant, other infectious diseases and malignancies, is discussed. PMID- 8493953 TI - Cytologic diagnosis of respiratory syncytial virus infection in a bronchoalveolar lavage specimen from a bone marrow transplant recipient. AB - Cytologic examination of a bronchoalveolar lavage specimen from a 6-year-old bone marrow transplant recipient revealed pulmonary infiltrates and occasional cells containing discrete pink cytoplasmic inclusions on a May-Grunwald-Giemsa stain. Direct immunofluorescence stains of cytospins prepared from the same specimen were positive for respiratory syncytial virus (RSV). Electron microscopy revealed occasional epithelial cells with cytoplasmic inclusions composed of filamentous virions. The patient died 6 months after the specimen was taken. An autopsy showed ongoing bronchiolitis with diffuse alveolar damage. Occasional bronchiolar epithelial cells contained discrete eosinophilic cytoplasmic inclusions, which on ultrastructural examination proved to be compatible with RSV. Examination of bronchoalveolar lavage fluid from bone marrow transplant recipients should include a search for cytopathic changes compatible with RSV infection. Electron microscopy can be helpful in confirming this diagnosis. PMID- 8493954 TI - Kasabach-Merritt syndrome with profound platelet support. AB - The Kasabach-Merritt Syndrome describes thrombocytopenia occurring in patients with giant hemangiomata. The resultant thrombocytopenia may be profound and occasionally even life-threatening. An 11-month-old infant with prolonged thrombocytopenia whose course was complicated by recurrent hemorrhaging requiring intense platelet transfusions is reported. During her 19-month hospitalization she received 6,622 platelet concentrates. This represents the most extensive platelet support ever given to an infant with this syndrome. PMID- 8493955 TI - Integrating information from decentralized laboratory testing sites. The creation of a value-added network. AB - The decentralization of laboratory testing provides distinct advantages for clinicians and patients, such as the reduction of test turnaround time, but also promotes the development of scattered caches of results. This problem could be ameliorated by the creation of an integrated laboratory data base. Such an approach would provide clinicians with a patient view of laboratory information in addition to the functional view of it that is offered currently. Impressive technologic advances are being made in the development of a distributed computer architecture in which processing tasks and information are shared across multiple hardware platforms attached to a network. Such architecture could be used to create a regional value-added laboratory network to integrate test information generated in decentralized testing sites. Independent reference laboratories and tertiary-care referral hospitals are the most likely candidates to create distributed value-added networks. Pathologists should view themselves as health care professionals responsible for the processing, storage, and transmission of information, as well as for its generation. In time, the partition of information along hospital geopolitical boundaries will appear archaic and will be replaced by an emphasis on local and regional integration of medical information similar to that advocated here. PMID- 8493956 TI - Fine-needle aspiration biopsy and breast cancer. PMID- 8493957 TI - Fine-needle aspiration of fibroadenoma-like carcinoma. PMID- 8493958 TI - Transmission of hepatitis after the administration of intravenous immunoglobulins. PMID- 8493959 TI - A review of pulmonary pathology and mechanisms associated with inhalation of freebase cocaine ("crack"). AB - The use of cocaine in the United States has reached near epidemic proportions. A major factor responsible for the dramatic increase in cocaine use is the ability to freebase cocaine and extract essentially pure drug to be smoked as crack. As a result, a variety of respiratory problems temporally associated with crack inhalation have been reported. Cocaine may cause changes in the respiratory tract as a result of its pharmacologic effects exerted either locally or systemically, its method of administration (smoking, sniffing, injecting), or its alteration of central nervous system neuroregulation of pulmonary function. These changes include such diverse disorders as thermal airway injury, pulmonary edema and hemorrhage, hypersensitivity reactions, and interstitial lung disease. However, a review of the pulmonary pathology and dysfunction associated with crack and/or cocaine use indicates that the reported changes are most likely multifactorial, even idiosyncratic, and fails to reveal common features diagnostic of cocaine use. It is likely that the spectrum of cocaine-induced pulmonary disease will continue to enlarge. PMID- 8493960 TI - Pressure sores in a Christian Science sanatorium. AB - We reviewed the Dallas County Medical Examiner's Office records of all individuals who had died in a local Christian Science Sanatorium during a 5 1/2 year period. Of 116 such patients, only 13 (11%) had pressure sores (decubitus ulcers). In 10 of these patients, the sores were described as small, superficial, and/or healing, while the other three patients had more serious ulcers. In contrast, for patients dying in nursing homes or hospitals, the incidence of pressure sores may be as high as 54-57%. It is our opinion that the difference in incidence is due to the personal and conscientious nursing care provided by Christian Science institutions. PMID- 8493961 TI - A review of fatal injuries associated with downhill skiing. AB - Reviewed here are those circumstances surrounding 18 downhill skiing deaths in Alberta, Canada. Variables that elevate the risk of injury and death are highlighted. This study profiles the fatally injured skier. The individual most likely to die while downhill skiing is an experienced male skier, average age 31 years. He loses control while skiing too fast and strikes an object, resulting in fatal blunt trauma injuries. The ability to define characteristics of the individual at risk of a fatal ski injury is important to the design and implementation of injury prevention programs. Public education targeted to those at risk may reduce the incidence of death and injury in downhill skiing. PMID- 8493962 TI - A review of 19 fatal injuries associated with backcountry skiing. AB - A review of circumstances surrounding 19 backcountry deaths in Alberta, Canada, between 1980 and 1991 suggests several factors that increase the risk of injury or death. This study provides a descriptive profile of a fatally injured backcountry skier and the circumstances surrounding his or her death. The individual most likely to suffer a fatal injury while participating in a backcountry ski activity is a 36-year-old man. He is typically an experienced backcountry skier who chooses to ski in areas where the avalanche hazard is known to be moderate to extreme. Delineating the personal characteristics of those at risk for backcountry injury and identifying situations that put them at risk will enable better design of education programs. Targeting high-risk groups may also reduce the incidence of death from this activity. PMID- 8493963 TI - A review of fatal bear maulings in Alberta, Canada. AB - Occasionally, encounters with a grizzly or a black bear have proved fatal. We describe the characteristics of fatal bear maulings and the circumstances that provoked them. The actions of wild bears are compared with those of bears that have become comfortable around people (wild/"habituated" bears). A description of eight deaths that occurred in the province of Alberta, Canada, between 1973 and 1988 will underscore the above. PMID- 8493964 TI - Horse-related fatalities in the Province of Alberta, 1975-1990. AB - People use horses for work and recreational purposes on farms and ranches in Alberta, Canada. This retrospective descriptive review examines the records of all those people killed while around horses between 1975 and 1990. The intent is to ascertain features common to these injuries and to suggest prevention strategies. Records from the Office of the Chief Medical Examiner of Alberta revealed that 38 people were involved in horse-related fatalities between 1975 and 1990 and that 22 died of head injuries. All 38 deaths were classified as accidental. Some of these might have been prevented, or injuries might have been minimized by riders' wearing approved riding helmets. Public education encouraging the proper use of protective headgear is necessary if there is to be a reduction in the severity of these injuries. PMID- 8493965 TI - BLURBs. A coding scheme for toxicologic data. AB - A simple scheme is presented to enable coding of toxicologic data by medical examiners or coroners who can design or direct the structure of their computer databases. Based on the English language, BLURBs are created, which consist of a prefix describing the specimen, a root word indicating the substance analyzed, and a suffix indicating the test results. BLURBs are easily interpretable and can reduce computer disk space usage, facilitate useful queries, and promote uniformity of data. PMID- 8493966 TI - Automation of medical examiner offices. AB - General information and principles regarding the automation of medical examiner and coroner offices are presented. Topics discussed include the importance of using available resource groups, questions that should be answered to determine the need for automation, the importance of specifically defining office needs and goals prior to automation, the value of capturing data in multiple ways, the importance of maintaining some hardcopy files, the value of ensuring capability to modify and enlarge the computer system, the need to tailor systems to the needs of specific offices, possibilities for generating money or acquiring equipment at little or no cost, the use of personal computers and commercially available software, the value of having all operations inhouse, transition to new operating systems and environments, and the foreseeable use of emerging technologies. PMID- 8493967 TI - Jurisdiction on military installations. AB - The death of an individual on a military installation often raises the question of who has the authority to investigate that death and perform an autopsy. The answer to this question depends upon whether jurisdiction is exclusively federal or is shared by the state and federal governments. Jurisdiction can be determined by contacting the installation's Directorate of Engineering and Housing or the legal office. When there is exclusive federal jurisdiction, the installation commander or the Armed Forces Medical Examiner may authorize an autopsy on a military member. Under certain conditions, the installation commander may authorize an autopsy on a civilian, especially where a legitimate connection exists between that civilian and the federal government. When jurisdiction is concurrent (that is, shared by the state and federal governments), the civilian medical examiner may waive jurisdiction to the military, but only as to the death of a military member. The authority to investigate the death of a civilian (whether a military dependent or not), to include autopsy examination, is exclusively civilian when jurisdiction is concurrent. Overseas locations are controlled by special agreements that in general, give the U.S. government jurisdiction over military members, their dependents, and U.S. civilian components of the assigned force. PMID- 8493968 TI - Misclassification of deaths caused by cocaine. An assessment by survey. AB - The use of U.S. vital statistics for surveillance of drug-related mortality may be limited by the way in which certifiers complete death certificates and by the constraints of the International classification of diseases, Ninth Revision (ICD 9). ICD-9 is the system used by the National Center for Health Statistics (NCHS) to compile national, cause-specific mortality data from information reported on death certificates. To investigate the extent of variability in certification practices among medical examiners (MEs), we conducted a mailout survey in which we asked a national sample of 49 MEs to review summaries of 28 death scenarios and, for each death, assign the cause and manner of death. Cocaine use was the unequivocal cause of death for 17 of the 28 deaths. We then asked a nosologist at NCHS to code the verbatim survey responses in accordance with the rules and rubrics of the ICD-9 system. Of the 20 MEs who responded, 14 provided complete cause and manner determinations. For the cocaine-caused deaths, the 14 respondents provided 238 cause-of-death statements; 220 (92.4%) explicitly mentioned cocaine. However, only 45 of the 238 responses (18.9%) led to a cocaine specific ICD-9 code for the underlying cause of death. Our findings illustrate how death certification practices, coupled with the ambiguities of the ICD-9 system, may lead to substantial loss of detail about cocaine-caused deaths and misclassification of these deaths in official compilations of mortality statistics. PMID- 8493969 TI - Tissue distribution of ibuprofen in a fatal overdose. AB - A 26-year-old white man was found dead near his home. The decedent had had a history of ibuprofen overdose and had recently received a physician's order for 800 mg ibuprofen every 4 h for back pain. Postmortem examination was performed and was unrevealing except for heavy lungs (1,140 g combined weight) and a brownish-white granular residue in the stomach. Samples of heart blood, femoral blood, liver, brain, and gastric contents were submitted for toxicological analysis. Qualitative screening detected only the presence of ibuprofen. Quantitation of ibuprofen was performed using reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet detection. The analytical column was an Econosphere C-8 column (150 mm, 4.6 mm I.D.) with 5 microns particle size preceded by a C-8 5 microns guard column. The mobile phase was 46% methanol and 54% 0.2 M acetate buffer at a flow rate of 2 ml/min. Fenoprofen was used as an internal standard at 200 mcg/ml. A linear response (r = 0.99) was achieved over a concentration range of 25-600 mcg/ml. Ibuprofen was identified and quantitated in the following tissues: heart blood (518.0 mcg/ml), femoral blood (348.3 mcg/ml), liver (942.1 mcg/g), brain (283.9 mcg/g), and gastric contents (131 mg total). PMID- 8493970 TI - A case of fatal ingestion of malathion. AB - We report a case of suicide due to organophosphate poisoning in an 80-year-old woman who ingested malathion mixed with a fruit drink. She presented with signs and symptoms of cholinergic crisis and initially improved with therapy. Her plasma cholinesterase (ChE) level remained low, her course progressively deteriorated with respiratory and renal failure, and she died 12 days after hospital admission. The antemortem blood malathion level of 23.9 mg/L is the highest reported in the literature, as determined by modern methods. Postmortem toxicologic analysis revealed still greatly reduced ChE activity. PMID- 8493971 TI - Homicide with a captive bolt pistol. AB - A homicide with a captive bolt pistol (slaughterer's gun) is reported. The construction and the function of this "humane killer" as well as the typical patterns of injury are described. PMID- 8493972 TI - Shotgun pellet embolism to the brain. AB - This report describes the autopsy findings in a young man who died after having been shot with a shotgun from about 30 m. Although not suspected clinically, a right middle cerebral artery territory infarct was found; its cause was shown to be a shotgun pellet embolus that had lodged just proximal to the trifurcation of the right middle cerebral artery. The case underscores the importance of performing a thorough postmortem examination, including a careful study of cerebral vasculature, in instances of brain infarction. PMID- 8493973 TI - Laceration of vertebral artery. An historic boxing death. AB - An historic case of a boxing death (c. 1913) was reviewed, since the cause of death given at the time is now deemed incorrect. Using current literature on traumatic basal subarachnoid hemorrhage, the cause of death is now hypothesized to have been a tear in the right vertebral artery associated with hyperextension and rotation of the neck. PMID- 8493974 TI - Homicide offenders in Auckland, New Zealand. AB - In the 14-year period from 1976 to 1989, 183 homicide offenders have been recorded in Auckland, New Zealand. Data accessed from police files show that Maori and Polynesians made up the majority of the offenders. Almost all offenders were male, and the largest proportion was between 20 and 24 years of age. Racial differences were noted in the methods used to commit the homicide, in the offender-victim relationship, and in whether the offender acted alone. The majority of offenders were not convicted of murder, but were convicted on lesser charges. PMID- 8493975 TI - Fatal and near-fatal autoerotic asphyxial episodes in women. Characteristic features based on a review of nine cases. AB - As asphyxial episodes during autoerotic activity are rarely reported in women, a review of eight fatal cases and one near-fatal case was conducted to delineate more clearly the characteristics of this syndrome in women. Six cases involved characteristic fatal autoerotic asphyxial activity. The remaining two fatal cases were atypical in that the apparatus that was used for sexual purposes was not intended to cause asphyxia in one case and did not directly cause asphyxial death in the second case. The final case was not fatal. Significantly, the majority of women did not use unusual clothing, props, or devices to augment their activity, for example, five were completely naked and only one was found with elaborate clothing and extra ligatures. Six of the fatal cases had objective evidence of sexual activity, three had used neck padding to prevent chafing, and eight had failed self-rescue mechanisms. Of note, the initial impression in four cases (44%) was homicide (two), attempted suicide (one), and accidental death during sexual activity with a partner (one). These results support the assertion that the manifestations of female autoerotic asphyxial activity reported to date may be initially misleading to investigators. Our purpose in presenting these findings, therefore, is to increase awareness of the more subtle features of this syndrome in women in an attempt to reduce the potential for underdiagnosis or confusion with nonaccidental death in future cases. PMID- 8493976 TI - Accidental deaths from asphyxia. A 10-year retrospective study from Sweden. AB - Accidental mechanical asphyxia is an unusual cause of death. In reviewing 73 cases occurring during a 10-year-period in Sweden, young boys and elderly women seemed to be most prone to this type of fatality. A striking number of victims had deliberately put a noose-like structure around the neck, and yet another group became entangled in some part of their clothing. Thoracic immobilization was seen in a number of cases, also involving work-related accidents. Hospitalized patients, asphyxiophilics and inebriated victims represent other risk groups. A case involving the use of a helmet is reported in view of the growing frequency with which Swedish children use bicycle helmets. The material contains only a few cases where the victim was not alone at the time of the accident, and it seems plausible that supervision could have prevented many of the reported fatalities. Public knowledge of accident mechanisms may increase the awareness of hazardous situations and activities. Spreading of the medical examiner's knowledge may thus form a basis for accident prevention. PMID- 8493977 TI - Survival in hanging. AB - Although hanging is a popular means for suicides in India, the attempt frequently does not result in death. Of 12 cases of hanging, only one of which was accidental, seen at our institution during 1985-90, all but two victims survived. We present data indicating that hanging victims can be resuscitated even after prolonged periods of suspension and unconsciousness, and we discuss some of the reasons why asphyxiation by hanging may be delayed when there is no damage to the spinal cord. PMID- 8493978 TI - Sharpening of autopsy tools. AB - This article describes basic tool-sharpening techniques in which grinding wheels, files, abrasive papers, stones, strops, and steels are used to repair and sharpen the edges of autopsy tools including chisels, knives, scissors, and shears. In general, files or grinding wheels are used to repair edges with gross defects such as burrs, nicks, or chips, or to restore the bevel of an edge, and then a stone is used to sharpen the edge; whereas abrasive paper, strops, or steels are used to remove rust or oxidation products and to touch up an already sharp edge immediately prior to use. Although pathologists may prefer to delegate the sharpening of tools to others or to buy new tools when old ones become dull, there may be occasions when knowledge of sharpening techniques is beneficial either to sharpen a tool or to ensure that proper sharpening techniques are used by others. PMID- 8493979 TI - Reye's syndrome. PMID- 8493980 TI - External beveling of an entrance gunshot wound to the skull. PMID- 8493981 TI - External beveling of an entrance gunshot wound to the skull. PMID- 8493982 TI - Three cases of familial hairy cell leukemia. AB - In a 10-year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a "specific HLA antigen" and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia. We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH: Cancer 65:319-321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR: Leuk Res 11:1027-1028, 1987). Based on these observations, we may conclude that a "specific HLA type," A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia. PMID- 8493983 TI - Selection of a new generation of orally active alpha-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload. AB - The prospect of selecting oral alpha-ketohydroxypyridine chelators intended for clinical use in iron overload has been examined using several animal models of efficacy and toxicity. Studies using iron dextran-loaded mice labelled with 59Fe have shown that only the 1-substituted methyl, ethyl, (n)propyl, allyl, cyclopropyl, 2'-methoxyethyl, 3'-ethoxypropyl, or 2-methyl- or 2-ethyl-3 hydroxypyrid-4-one chelators were orally effective in increasing iron (59Fe) excretion by comparison to intraperitoneally administered desferrioxamine at the same dose (250 mg/kg). In contrast, chelators containing -H, mono- or dihydroxyalkyl and diethoxyethyl 1-substituents caused very little or no increase in iron (59Fe) excretion by the oral or intraperitoneal routes. In vitro studies using ferritin and haemosiderin have shown that equivalent iron release took place with both groups of chelators irrespective of their in vivo effects. In most cases there was no correlation between the n-octanol/water partition coefficient (Kpar) and iron removal efficacy but positive correlation between the lipophilicity and acute or subacute toxicity of these chelators in rats. The most toxic chelator in the chronic toxicity studies in rats was the lipophilic 1,2 diethyl-3-hydroxypyrid-4-one (EL1NEt). The most effective chelator in increasing iron excretion in mice and rabbits was 1-allyl-2-methyl-3-hydroxypyrid-4-one (L1NAII), and the chelator with the highest safety margin in mice and rats was 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Overall the oral effectiveness in increasing iron excretion by these chelators in animals does not appear to be related to their lipophilicity or their ability to mobilise polynuclear iron in vitro but rather to other properties possibly related to their rate of biotransformation and excretion. PMID- 8493984 TI - Prevention of hypermenorrhea with leuprolide in premenopausal women undergoing bone marrow transplantation. AB - We report on the use of leuprolide to prevent heavy menstrual bleeding that often occurs before platelet engraftment in premenopausal women undergoing bone marrow transplantation (BMT). Leuprolide, a synthetic analog of gonadotropin-releasing hormone (Gn-RH-a), was given to 34 patients by intravenous bolus injection, 1 mg daily, until platelet recovery. The median duration of therapy was 50 days (range 16-170). When necessary, patients self-administered the drug after discharge from the hospital. No adverse effects could be related directly to the use of leuprolide. Leuprolide effectively prevented menstruation in 25 patients (73%), failed in seven (21%), and two patients were not evaluable. The success of leuprolide therapy was related to the time of onset of treatment, as anticipated from the gradual effect of Gn-RH-a on the menstrual cycle. The failure rate was only 6% (one of 16 patients) when leuprolide was started at least 2 weeks prior to the development of thrombocytopenia, compared to a failure rate of 33% (six of 18 patients) when leuprolide was started at a later time. We conclude that leuprolide as a single agent is a safe and effective method to prevent menstrual bleeding during BMT. Additional studies are needed to determine the best timing for the onset of therapy and the relative benefit of leuprolide compared to other prophylactic approaches in patients with lengthy thrombocytopenia. PMID- 8493985 TI - Viridans streptococcal shock in bone marrow transplantation patients. AB - We have recognized a rapidly progressive, often fatal shock syndrome associated with viridans streptococcal sepsis following bone marrow transplantation (BMT). Of 832 patients receiving a marrow transplant at the University of Minnesota between 1976 and 1988, including 123 with viridans streptococcal bacteremia, 10 patients (8%) developed clinical shock within an average of 2 days (range 0-4 days) of their first positive blood culture. Viridans streptococcal shock occurred in patients early in the transplantation course, between 1 and 28 (median 6) days following BMT when all 10 patients were neutropenic. Six of the 10 patients died as a consequence of their shock or from subsequent complications. The most frequent (6 of 10 patients) viridans streptococcal species isolated in the shock patients was Streptococcus mitis. Of multiple factors analyzed for increased risk of developing viridans streptococcal shock, only younger patient age was significantly associated with the development of shock. Although 58% of BMT recipients with viridans streptococcal bacteremia were younger than 15 years, all 10 patients comprising the shock population were < 15 years of age (P < 0.02). We speculate that certain streptococcal strains may trigger fulminant shock in the immunocompromised BMT patient. PMID- 8493986 TI - Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia. AB - A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. PMID- 8493987 TI - Unstable alpha-chain hemoglobin variants with factitious beta-thalassemia biosynthetic ratio: Hb Questembert (alpha 131[H14]Ser-->Pro) and Hb Caen (alpha 132[H15]Val-->Gly). AB - Hb Questembert [alpha 131(H14)Ser-->Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an alpha-/beta-labeling ratio similar to that of beta-thalassemia trait. Hb Caen [alpha 132(H15) Val-->Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled beta-chains from the abnormal hemoglobin, thus leading to an apparent suppression of beta-chain synthesis, or 3) to a modified stability of the abnormal alpha-globin mRNA. PMID- 8493988 TI - Loss of high-responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: a report from the Multi-Center Hemophilia Cohort Study. AB - To evaluate the effects of human immunodeficiency virus type 1 (HIV-1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV-1-infected participants enrolled in a natural history study of HIV-1 infection in hemophilia. Fifty-six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high-responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3-46.3 years of age) were in the advanced stages of HIV-1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1-57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262-935/mm3) at the time of factor VIII rechallenge. Follow-up inhibitor titers were negative 7-42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV-1 infected patients who have a history of high-responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV-1 disease. PMID- 8493989 TI - Antiphospholipid antibodies in sickle cell disease. AB - Antiphospholipid antibody formation can be induced in mice by phospholipid in a hexagonal II phase but not by phospholipid in a bilayer phase. Since sickle red cell membranes have increased hexagonal II phase content, we have measured serum antiphospholipid antibody levels in 25 patients with sickle cell disease to determine whether anti-phospholipid antibody may similarly be induced in these patients. Seventeen of the 25 patients (68%) had increased levels of antiphospholipid antibodies. Eleven patients (65%) had IgG and six each (35%) had IgM and IgA isotypes. Antiphosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidic acid were the most frequently increased antibodies. The finding of increased antiphospholipid antibodies in these patients is compatible with the concept that antiphospholipid antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in the red cells of patients with sickle cell disease. PMID- 8493990 TI - Factor V inhibitor in thrombosis. AB - A 68-year-old previously well woman developed sudden onset of limb gangrene in association with liver dysfunction. An immediately acting inhibitor to factor V with some of the features of lupus anticoagulant was demonstrated. The patient required limb amputation within 2 weeks and activity of the anticoagulant seemed to be on the decline 6 months later. PMID- 8493991 TI - In vitro activity of chloroquine and quinine in combination with desferrioxamine against Plasmodium falciparum. AB - The activity of chloroquine and quinine, alone and in combination with desferrioxamine (7 mumol/liter), was evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum by a semimicroassay system. The addition of desferrioxamine had no effect on the activity of chloroquine against both clones. Desferrioxamine had no effect on the activity of quinine against the susceptible clone but had slightly enhanced quinine action against the resistant clone. Further development of desferrioxamine as an antimalarial drug may be of limited interest. PMID- 8493992 TI - Acquired immunodeficiency syndrome presenting as marrow cryptococcosis. AB - Disseminated cryptococcal infection is an uncommon initial manifestation in patients with the acquired immunodeficiency syndrome. The most common sites of involvement by cryptococci are the central nervous system and the lungs, and involvement of the marrow is rare. There are few descriptions in the literature on the cytologic findings of marrow cryptococcosis. We report a patient with disseminated cryptococcosis in which cytologic examination of the marrow provides the first clue to the diagnosis. PMID- 8493993 TI - Dysfunctional platelet glycoprotein IIb/IIIa associated with a platelet release defect: a family study. AB - We are reporting on a 36-year-old white female with a bleeding history attributed to dysfunctional platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and a coexisting platelet release defect. Platelet aggregation studies (PAS) revealed markedly diminished to absent responses to ADP, epinephrine, collagen and arachidonic acid; the ristocetin response was normal. ATP content was normal with poor release to the agonists as measured by luminescent technique. DDAVP infusion shortened bleeding time from 13.5 min to 8.0 and 12 min (at 1 and 2 hours). Flow cytometry and immunoblotting revealed normal amounts of GPIIb and diminished GPIIIa (50% of control). Using a previously reported ELISA which measures the binding of GPIIb/IIIa to immobilized fibrinogen, the patient's platelet extract showed no binding to fibrinogen. Both the father and mother were found to have decreased PAS responses and normal amounts of GPIIb/IIIa determined by both Western blot and flow cytometry. However, the ELISA showed decreased binding of their GPIIb/IIIa to fibrinogen (71% and 62% as compared to controls, respectively). The patient's dysfunctional fibrinogen receptor was clearly demonstrated by the ELISA. The parents had moderately reduced GPIIb/IIIa function in this assay, but they did not demonstrate a reduced GPIIIa as was noted in the patient. The parents' PAS indicated a platelet release defect. These findings suggest an inherited platelet release defect and a dysfunctional GPIIIa. The partial response to DDAVP would be compatible with the presence of a platelet release defect. PMID- 8493994 TI - Pyridoxine responsive hereditary sideroblastic erythropoiesis and iron overload: two microcytic subpopulations in the affected male, one normocytic and one microcytic subpopulation in the obligate female carrier. AB - Mild hepatic iron overload has been demonstrated by magnetic susceptibility measurements in a 22-year-old man with hereditary sideroblastic erythropoiesis despite hemoglobin levels in the normal range and a normal erythropoietin level. His grandfather's sideroblastic anemia has been found to be responsive to pyridoxine; his mother's hemoglobin has persisted in the normal range but red cell volume distribution analysis demonstrated two subpopulations; 30% with estimated geometric mean of 68 fl and 70% an estimated mean of 93 fl. Red cell distribution analysis of the grandson demonstrated two microcytic subpopulations; 46% with an estimated geometric mean of 45 fl and 54% an estimated mean of 70 fl. A therapeutic regimen is outlined to reduce to normal his iron stores and to prevent the future development of excessive iron overload. PMID- 8493995 TI - Interleukin-5 mRNA in three T-cell lymphomas with eosinophilia. AB - The objective of this controlled pilot study was to determine if mRNA coding for interleukin-5 (IL-5), a cytokine that promotes eosinophil differentiation, growth, and migration, could be detected in three T-cell lymphomas that were infiltrated extensively by eosinophils. To detect mRNA coding for IL-5, we performed an RNA polymerase chain reaction on mRNA extracted from three T-cell lymphomas with eosinophilia and from 29 positive and negative validation controls. Using this procedure, we detected a 293-base pair, IL-5-specific amplification product in the three cases of T-cell lymphoma with eosinophilia and in 11 of 12 positive validation controls, including 10 cases of Hodgkin's disease with eosinophilia. IL-5 mRNA was not detectable in the 17 negative validation controls. This preliminary study suggests that IL-5 mRNA is detectable by polymerase chain reaction in three cases of T-cell lymphoma with eosinophilia. PMID- 8493996 TI - Response to commercial factor VIII concentrate. PMID- 8493997 TI - Cyclosporin A for Diamond-Blackfan anemia: a new case. PMID- 8493998 TI - Heterozygous beta-thalassemia: relationship between the hematological phenotype and the type of beta-thalassemia mutation. PMID- 8493999 TI - Subcutaneous localizations of Burkitt lymphoma after celioscopy. PMID- 8494000 TI - Lymphocyte counts versus percentages. PMID- 8494001 TI - Oral psoralen photochemotherapy (PUVA) for pruritus associated with polycythemia vera and myelofibrosis. PMID- 8494002 TI - Circulating mast cells in acute myelomonocytic leukemia with eosinophilia. PMID- 8494003 TI - Splenic lymphoma with circulating villous lymphocytes simulating plasma cell leukemia. PMID- 8494004 TI - Hemoglobin Korle-Bu (G-ACCRA) in combination with hemoglobin C. PMID- 8494005 TI - An unusual and unreported toxicity to erythropoietin. PMID- 8494006 TI - Aging, hypertension, and renal damage: generalities and results of the Cardiovascular Study in the Elderly. PMID- 8494007 TI - The effects of various antihypertensive agents on cardiovascular risk factors in patients with renal failure. AB - Systemic cardiovascular diseases are the most important cause of morbidity and mortality among patients with chronic renal failure. Hypertension, lipid-profile abnormalities, glucose intolerance, and left ventricular hypertrophy are found in most patients with chronic renal failure and are responsible for the increased incidence of atherosclerosis. Hypertension is the risk factor most susceptible to treatment, but consideration must be given in selecting an antihypertensive agent not only to its effect on blood pressure but to its effects on the other risk factors. Improper selection could impair the long-term benefit of good blood pressure control by increasing the severity of the other cardiovascular risk factors and eventually worsening the prognosis of the chronic renal failure. The remaining renal function in patients not yet in end-stage renal failure deserves special consideration; an adequate antihypertensive regimen could potentially delay the need for dialysis. PMID- 8494008 TI - Have rational therapeutic principles emerged in treating hypertension in chronic renal failure? PMID- 8494009 TI - Morbidity and mortality due to hypertension in patients with renal failure. AB - The incidence of, and the mortality from, cardiac disease is strikingly increased in dialysis patients. Coronary disease existing prior to the onset of dialysis is an important determinant of ischemic heart disease (IHD) on dialysis. Death from IHD on dialysis is higher by factor 5-20 than in the general population. In several studies either a marginal or no relation between blood pressure on admission to renal replacement therapy, or average predialysis blood pressure and cardiac death has been noted. In other studies blood pressure was, however, predictive of IHD. Such discrepancies may be explained by a low-risk threshold, a nonlinear relationship, and the necessity to examine large patient cohorts to document the effect. Of great importance may be the potentially increased susceptibility of the heart to hypertensive injury and ischemia. This may be related to factors like left ventricular hypertrophy, cardiac fibrosis and altered cardiac mechanical properties, diminished coronary reserve, and reduced ischemia tolerance, particularly during intradialytic hypotensive episodes due to compromised microcirculation and disturbed insulin-induced glucose uptake and abnormalities of autonomous neural innervation of the heart. PMID- 8494010 TI - The place of hypertension among the risk factors for renal function in chronic renal failure. PMID- 8494011 TI - Hypertension and chronic renal insufficiency: the experience of the Northern Italian Cooperative Study Group. AB - There is general agreement that hypertension is a prognostic index of the progression of chronic renal insufficiency (CRI), although it remains to be clarified whether this is related to the hypertension per se, or to the underlying disease and the level of CRI. In an attempt to clarify this important point, an inductive analysis was made of the behavior of blood pressure values and their relationship to the progression of CRI in 456 patients (pts) who participated in a multicenter prospective formal randomized trial, designed to compare the effects of a restricted and a controlled protein diet on CRI progression. An analysis was also made (on the population as a whole and by separating the pts into fast progressive and slowly progressive groups) of the type and frequency of the antihypertensive drugs used, the number and type of drugs used in association, and their possible relationship to the progression of CRI. Of the 456 enrolled pts, 406 (89%) were defined as hypertensive at entry (mean blood pressure > 107 mm Hg); 324 out of the 380 pts (85.3%) who completed the 24-month follow-up or reached an end point were treated with antihypertensive drugs. There was a significant difference at entry between the supine blood pressure values of the pts with fast progressive CRI (182 pts), and those of the pts with slowly progressive CRI (198 pts). During the follow-up period, no significant differences were observed between the two groups. There was no difference in the blood pressure levels reached with the different drugs used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494012 TI - Effects of blood pressure and antihypertensive treatment on progression of advanced chronic renal failure. AB - The potential role of blood pressure and antihypertensive treatment on the progression of advanced chronic renal failure was analyzed in 223 adult patients (126 males) with well-defined primary chronic renal diseases (glomerulonephritis, n = 73; angionephrosclerosis, n = 24; interstitial nephritis, n = 61; polycystic kidney disease, n = 52, Alport's syndrome, n = 13). Effect of average mean arterial pressure (MAP) obtained during follow-up, antihypertensive treatment (normotensive, conventional antihypertensive treatment, angiotensin-converting enzyme inhibitors [ACEI]), gender, type of the nephropathy, age, body mass index, and protein intake were analyzed using a multivariate analysis of variance. Mean arterial pressure was significantly and independently correlated with duration (r = -0.40, P < 0.0001) and slope of creatinine clearance (delta Ccr; r = 0.32, P < 0.0001). Mean arterial pressure and antihypertensive treatment could predict 25% of the variation in duration. Gender, type of the nephropathy, and MAP were able to predict 30% of the variation in delta Ccr. When analyzing results by type of nephropathy, MAP was significantly and inversely correlated with duration in glomerulonephritis (r = 0.29, P < 0.05), and positively with delta Ccr in angionephrosclerosis and interstitial nephritis (r = 0.49, P < 0.05 and r = 0.36, P < 0.01, respectively). In each type of nephropathy, conventional antihypertensive treatment and ACEI had grossly similar effects upon duration and slope except. In conclusion, blood pressure level is an important contributor to progression of chronic renal failure but its effect was more evident in angionephrosclerosis and interstitial nephritis at the extreme values of blood pressure distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494013 TI - Hemodynamic alterations and urinary albumin excretion in patients with essential hypertension. AB - Salt-sensitive animals as well as patients with essential hypertension appear to have a greater propensity to develop renal disease as a consequence of hypertension. They also manifest an abnormal renal hemodynamic adaptation to changes in dietary sodium intake and blood pressure. This suggests that the two may be related. Some patients with essential hypertension manifest an increase in urinary albumin excretion (UAE). It is uncertain whether this is more common in salt-sensitive patients and whether it represents a marker for progressive renal disease. The effect of antihypertensive agents on UAE varies substantially depending on the agent used, and it is not necessarily related to the antihypertensive action. Whether antihypertensive agents that more effectively reduce UAE may also result in greater renal protective effects remains to be established. PMID- 8494014 TI - Genetics of renal damage in primary hypertension. AB - Little is known of the genetics of glomerular damage in essential hypertension in humans. The prevalence of end-stage renal disease due to primary hypertension varies from 20% to 30% of all cases of renal failure to as low as 0.002%. This depends not only on differences in diagnostic criteria but also on different racial susceptibility to the disease as well as on different genetic backgrounds in different subsets of individuals of the same race. A review of the literature is provided, together with an example of how a point mutation that causes hypertension in Milan hypertensive rats can provide a model to analyze this issue correctly. PMID- 8494015 TI - The ischemic kidney and hypertension. PMID- 8494016 TI - Hypertension and pregnancy: impact of the Working Group report. PMID- 8494017 TI - Insulin resistance and hypertension: connections with sodium metabolism. PMID- 8494018 TI - Hypertension, hyperlipidemia, and renal damage. AB - Experimental studies have demonstrated that a number of factors participate in the progression of renal disease. Systemic and glomerular hypertension have been shown to be critical factors in renal injury. Hyperlipidemia that frequently coexists with renal disease also has been suggested as an important participatory factor in nephron damage. Interestingly, both hypertension and hyperlipidemia seem to evoke glomerular growth, a factor that has also been postulated to be involved in glomerular and tubular destruction. Recently, experimental and clinical data suggest that an important interaction occurs between hyperlipidemia and hypertension. Not only do they frequently coexist, but hypertension dramatically exaggerates hyperlipidemic injury, and hyperlipidemia alters systemic and glomerular vascular production of vasoactive substances which maintain basal vascular tone. Thus, these recent observations underscore the interactive potential of the various risk factors that participate in progression of renal disease. They also suggest that multiple interventional strategies may be needed to optimally prevent progressive nephron loss. PMID- 8494019 TI - Hypertension secondary to early-stage kidney disease: the pathogenetic role of altered cytosolic calcium (Ca2+) homeostasis of vascular smooth muscle cells. AB - We have examined cardiovascular pressor responsiveness to infused norepinephrine (NE) as related to endogenous plasma NE and plasma renin and to platelet free cytosolic (Ca2+) in 36 patients with early-stage kidney disease and 27 matched normal subjects. The 27 hypertensive patients and the normal subjects did not differ in blood volume, plasma renin, and NE; however, the hypertensive patients had a higher exchangeable body sodium content. Basal plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance for NE did also not differ significantly between the two study groups. In contrast, the threshold or pressor doses of infused NE significantly decreased in the patients with kidney disease. Antihypertensive pharmacotherapy with (Ca2+) channel blockers and/or loop diuretics normalized blood pressure and cardiovascular NE hyperresponsiveness and reduced blood volume, exchangeable body sodium, and platelet free cytosolic (Ca2+). In contrast, experimental digitalisation as a model for in vivo sodium/potassium adenosine triphosphatase inhibition augmented NE responsiveness and raised platelet free cytosolic (Ca2+). Incubation of platelets from normal subjects with plasma ultrafiltrate from hypertensive patients gave evidence for an endogenous factor capable to raise free cytosolic (Ca2+) and to act synergistically with digoxin. Hypertension secondary to early stage kidney disease is related to an impairment of sodium excretion leading to an expansion of blood volume and exchangeable body sodium. This may result in increased secretion of endogenous factors, leading to alterations of cytosolic (Ca2+) homeostasis of vascular smooth muscle cells followed by elevated peripheral resistance and thus blood pressure. PMID- 8494020 TI - Prevalence and significance of hypertension in systemic lupus erythematosus. PMID- 8494021 TI - Sodium-lithium countertransport activity in red blood cells of patients with IgA nephropathy. AB - In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearman's rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome. PMID- 8494022 TI - Nephron underdosing: a programmed cause of chronic renal allograft failure. AB - The findings cited in this report suggest that renal allograft survival might be improved by matching nephron supply to recipient needs (analogous to prescription dialysis based on Kt/V). Methods for assessing functional graft capacity (ie, nephron number, filtration, or total microvascular surface area) are needed. Graft weights might serve as a useful alternative until better indices are devised. Measures for defining and possibly reducing recipient demands are also needed to preserve graft performance. Where gross imbalances between nephron supply and recipient demand are not likely to be corrected over the long term by engraftment of a single kidney, consideration should be given to dual kidney transplantation, currently feasible only from cadaveric, but eventually from xenogeneic sources as well. The predicted longer survival and avoidance of premature return to end-stage renal disease with the transplantation of two kidneys in certain conditions could render this approach more rational, both in clinical and economic terms, than single kidney engraftment for those at greatest risk for shortened graft survival. The dosing of larger numbers of nephrons might also lessen the risk of coexistent hypertension and thereby reduce the magnitude and tempo of immune injury to the graft. PMID- 8494023 TI - Hypertension after renal transplantation. AB - In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential follow-up of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation (P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year (P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids (P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 +/- 9 versus 104 +/- 9 mm Hg) and 5 years (105 +/- 10 versus 108 +/- 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 +/- 0.4 versus 1.6 +/- 0.4 mg/dL) and 5 years (1.8 +/- 1 versus 1.9 +/- 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494024 TI - The role of hypertension as a damaging factor for kidney grafts under cyclosporine therapy. AB - The relative importance of glomerular filtration rate (GFR) and hypertension (permanent need for antihypertensive drugs) for the prognosis of kidney grafts was studied in 135 cyclosporine-treated primary cadaver kidney transplant recipients whose grafts lasted more than 1 year. The start point of 1 year after transplantation was chosen because hypertension developed within the first year in all our hypertensive patients. Graft prognosis in hypertensive patients was not significantly worse than that of normotensive patients; moreover at multivariate analysis, age at transplantation and GFR at 1 year (P = 0.014), but not hypertension, were significant prognostic factors for the graft. At logistic regression, GFR was a significant variable for hypertension (P = 0.009), but hypertension was not a significant variable for renal failure at 1 year (GFR < or = 0.83 mL/sec [50 mL n]; P, NS). Accordingly, hypertension per se resulted much more as a consequence of reduced renal function than as a direct cause of graft damage. However, when hypertensive patients were divided into controlled and uncontrolled, uncontrolled hypertensive patients had the worst prognosis (P = 0.03), and blood pressure control proved a strong prognostic factor for the graft, even after GFR was considered (P = value of the model considering blood pressure control, GFR, and age at transplantation: 0.007). Our data suggest that, apart from being an expression of reduced renal function, hypertension is also a direct kidney graft damaging agent, a role that can be controlled by strict reduction of blood pressure levels. PMID- 8494025 TI - The dilemma of benign nephrosclerosis: the hypertensiologist's view. PMID- 8494026 TI - The diagnostic dilemma of hypertensive nephrosclerosis: the nephrologist's view. AB - The appearance of progressive renal disease in elderly patients with essential hypertension, sometimes irrespective of blood pressure control, is frequently related to the association of hypertension and atheromatous renal disease. This disease may lead to renal failure through a renal artery stenosis and/or chronic microembolization into the kidney. Nonsevere uncomplicated essential hypertension is constantly associated with renal vascular changes that are qualitatively indistinguishable from those related to aging. Notwithstanding the fairly constant presence of so-called benign hypertensive nephrosclerosis in patients with established hypertension, only a subset of these patients show progressive renal damage. Three mechanisms of progression may be at play: (1) a combination of ischemic and hypertensive glomerular mechanisms in some susceptible humans; (2) nonhemodynamic factors such as local immune mechanisms; or (3) the involvement of metabolic abnormalities which favor glomerulosclerosis. PMID- 8494027 TI - Glaxo lecture: old and new concepts in the treatment of hypertension. PMID- 8494028 TI - How to treat the hypertensive patient with early renal damage. PMID- 8494029 TI - Molecular characterization of a complex translocation in a newborn infant. AB - A newborn infant was referred because of low-set ears, mild downward slant of the palpebral fissures, micrognathia with high-arched palate, a flat midface, small mouth, and thin upper lip with cupid bow configuration. To some extent her cry resembled that associated with cri du chat syndrome. Cytogenetic findings with G- and Q-banding alone failed to characterize precisely the complex translocations. By the chromosome in situ suppression (CISS) hybridization technique using whole chromosome specific probes, a complex 4 breakpoint rearrangement involving both arms of a single chromosome 1 with the long arms of chromosomes 5 and 11 was disclosed, i.e., 46,XX, der(1),t(1;5) t(1;11) (5qter-->5q31::1p31.3-->1q44::11q23 ->11 qter;5pter-->5q31::1p31.3-->1pter;11pter-- >11q 23::1q44-->1qter). Gene deregulation and position effect may explain the multiple anomalies in individuals with apparently balanced translocations. The molecular characterization of such cytogenetically balanced translocations may shed some light towards unveiling the clinical consequences associated with aberrations which are presumably balanced. PMID- 8494030 TI - Trisomy 22 confirmed by fluorescent in situ hybridization. AB - We report on a newborn girl with multiple congenital anomalies, whose G-banded chromosome analysis showed complete trisomy 22. Chromosome painting using a whole chromosome painting probe for chromosome 22 confirmed that neither chromosome 22 was involved in a cryptic translocation. PMID- 8494031 TI - Angelman and Prader-Willi syndrome: a magnetic resonance imaging study of differences in cerebral structure. AB - Recent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform "in vivo neuropathology." In this study we compared the cortical morphology in six children with Angelman and four with Prader-Willi syndrome. These two syndromes are of special interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader-Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome. PMID- 8494032 TI - Communication, cognition, and social interaction in the Angelman syndrome. AB - Persons with Angelman syndrome (AS) have mental retardation, epilepsy, and a characteristic "puppet-like" gait. Behaviorally, they are distinctive because they have no speech and have excessive laughter. A speech and communication evaluation of 7 persons with AS was performed to provide improved understanding of the speech deficit. Assessments included prelanguage and language development, oral motor abilities, and cognitive and social interaction skills. Results indicate that the typical lack of speech may not be due to mental retardation alone. Oral motor dyspraxia, and deficits in social interaction and attention were characteristic of AS and contributed to the lack of speech. PMID- 8494033 TI - Hypopigmentation in Angelman syndrome. AB - Chromosome region 15q is thought to contain one or more genes that are important for melanin pigment synthesis in the hair, skin, and eyes. Hypopigmentation has been identified in the Prader-Willi (PWS) and Angelman (AS) syndromes. We have examined 6 individuals with AS to further characterize the pigment pattern in this condition. The age of the 5 girls and one boy ranged from 2.4 to 7.0 years. None had obvious albinism. Hair color ranged from light blond to brown. Skin was type I in 3 and type II in 3. Eye changes included nystagmus in 2, strabismus in 4, and reduced retinal pigment in 5. The mean hairbulb tyrosinase activity was 0.37 +/- 0.44 pmol/hb/120 min for the individuals with AS, with a range of 0.00 to 1.13 (normal brown control 1.49 +/- 0.79, normal blond control 1.50 +/- 0.85). Electron microscopic examination of hairbulb melanocytes showed normal melanosome and melanocyte architecture and number, but reduced melanin formation, with many stage II and III premelanosomes but few stage IV fully melanized melanosomes. Hypopigmentation characterized by light skin, reduced retinal pigment, low hairbulb tyrosinase activity, and incomplete melanization of melanosomes is part of the phenotype of AS, and is similar to that found in PWS. PMID- 8494034 TI - Trisomy 22 and facioauriculovertebral (Goldenhar) sequence. AB - We report on an infant girl born with complete trisomy 22 and left hemifacial microsomia, ear anomaly, and limbal and epibulbar complex choristoma. Trisomy 22 was confirmed by prometaphase chromosome analysis and in situ hybridization. This patient extends the list of chromosome abnormalities associated with apparent Golenhar sequence and emphasizes the importance of chromosome analysis in the investigation of patients with this condition. A detailed ophthalmopathological investigation is reported. PMID- 8494035 TI - Identification of a cryptic t(5;7) reciprocal translocation by fluorescent in situ hybridization. AB - Fluorescent in situ hybridization (FISH) identified a cryptic balanced reciprocal translocation in the mother of an infant with the cri-duchat syndrome. A biotinylated probe from a flow-sorted chromosome 5 cosmid library was used to show the distal deletion of 5p15.2 in the propositus and a translocation of this segment to the distal end of 7 at 7p21 in his mother. In a subsequent pregnancy, the fetus was shown to have normal chromosomes using the same 5 cosmid library probe and a locus-specific probe derived from the 5p15.3 region. The importance of incorporating FISH into the routine diagnostic laboratory is discussed. PMID- 8494036 TI - Identification, counselling, and outcome of two cases of prenatally diagnosed supernumerary small ring chromosomes. AB - De novo supernumerary small ring chromosomes have mainly been reported in pediatric patients with clinical abnormalities, thus, there may be bias of ascertainment. Reports on prenatally diagnosed cases with postnatal follow-up are rare. With the availability of chromosome specific alpha-satellite centromeric probes, the interest in these previously unidentifiable supernumerary small ring chromosomes has been rekindled [Callen et al.: J Med Genet 27: 155-159, 1990; Callen et al.: Am J Hum Genet 48:769-782, 1991; Callen et al.: Am J Med Genet 43:709-715, 1992]. We report on 2 prenatal diagnosis cases, where a ring was noted in 25 and 60% of the amniocytes, respectively. The initial G- and C-banding in Case 1 allowed an assumption of a chromosome 1 origin of the extra chromosome. This was confirmed by fluorescence in situ hybridization (FISH) studies using the appropriate probes. No similar initial assumption could be made in Case 2; thus, random trials with multiple probes were performed. A chromosome 19 origin in Case 2 was eventually concluded. The large amount of C-band positive material on the extra chromosome and the normal level 2 fetal ultrasound examination suggested a favorable outcome in both cases, but the possibility of mental retardation could not be ruled out. An empiric risk figure with regard to prenatally diagnosed de novo supernumerary small ring chromosomes is not available. Although the decision making processes of the parents were different, they both decided to continue the pregnancy. At age 9 months and 1 1/2 years both children, a girl and a boy, showed normal growth and development. PMID- 8494037 TI - 46,XX,15p+ documented as dup (17p) by fluorescence in situ hybridization. AB - We report on a patient with a complex heart defect, short webbed neck, multiple other minor features, and a 46,XX,15p+ de novo karyotype. The enlarged short arm of the chromosome 15 was Distamycin-DAPI and C-band negative. Fluorescence in situ hybridization (FISH) using an alpha satellite probe from chromosome 15 demonstrated hybridization only to the normal 15. In situ hybridization using a set of probes that bind to the short arm (17p13) and centromere of chromosome 17 demonstrated that the extra material on chromosome 15, including the centromere, was derived from chromosome 17. Therefore, this patient has a duplication of the centromere and short arm of chromosome 17. Clinical manifestations in this patient were consistent with those in previously described patients with dup (17p). PMID- 8494038 TI - Method for sequential staining of GTL-banded metaphases with fluorescent-labeled chromosome-specific paint probes. AB - We describe a method for use of fluorescent-labeled whole chromosome-specific paint probes on GTL-banded metaphases to utilize the combined potential of these techniques for defining chromosome abnormalities. The efficacy of this method was tested on 6 cases involving different chromosome abnormalities and various tissues, including blood, amniotic fluid, skin fibroblasts, and bone marrow. PMID- 8494039 TI - Hepatic stem cells. PMID- 8494040 TI - Imaging of oxidative stress at subcellular level by confocal laser scanning microscopy after fluorescent derivatization of cellular carbonyls. AB - Confocal laser scanning fluorescence microscopy plus image videoanalysis was used to visualize the tissue areas and the subcellular sites first involved by oxidative stress and lipid peroxidation, in the well-established experimental model of lipid peroxidation induced by haloalkane intoxication in the liver cell. The fluorescent reagent 3-hydroxy-2-naphthoic acid hydrazide was employed to derivativize the carbonyl functions originating from the lipoperoxidative process in situ, in liver cryostat sections from in vivo intoxicated rats, as well as in isolated hepatocytes exposed in vitro to the pro-oxidant action of haloalkanes. The results obtained indicate that: 1) the detection of fluorescent derivatives of carbonyls indeed offers a gain in sensitivity, 2) haloalkane-induced lipid peroxidation in hepatocytes primarily involves the perinuclear endoplasmic reticulum, whereas the plasma membrane and the nuclear compartment are unaffected, and 3) lipid peroxidation also induces an increase of liver autofluorescence. PMID- 8494041 TI - Regulation of the differentiation of diploid and some aneuploid rat liver epithelial (stemlike) cells by the hepatic microenvironment. AB - Following intrahepatic transplantation in adult syngeneic Fischer 344 rats, diploid cultured rat liver epithelial cells (WB-F344), modified to carry the Escherichia coli beta-galactosidase reporter gene and/or the fluorescent membrane dye PKH26-GL, integrate into hepatic plates and acquire the size and nuclear structure of mature hepatocytes. Additionally, of two aneuploid, neoplastically transformed derivatives of WB-F344 cells, both of which produce aggressively growing tumors when transplanted subcutaneously, cells of one line (GN6TF) do not produce tumors in the liver but integrate into hepatic plates and morphologically differentiate. The other transformed line (GP7TB) retains tumorigenicity in the liver, but cells in the intrahepatic tumors are more differentiated morphologically than are tumors at subcutaneous sites. These results suggest that WB-F344 cells are stemlike cells for hepatocytes and that the hepatic microenvironment induces them to incorporate into hepatic plates and differentiate. Our results also suggest that the hepatic microenvironment regulates the differentiation of some neoplastically transformed hepatic stemlike cells, thereby eliminating or reducing their tumorigenic potential. PMID- 8494042 TI - Liver allograft rejection in sensitized recipients. Observations in a clinically relevant small animal model. AB - A sequential analysis of liver allograft rejection in sensitized rats using immunopathological and ultrastructural microscopy is described. Lewis rats were primed with four ACI skin grafts and challenged with an arterialized ACI orthotopic liver allograft 14 to 17 weeks later. The sensitization resulted in a mix of IgG and IgM lymphocytotoxic antibodies at a titer of 1:512 at the time of transplantation. Specificity analysis of pretransplant immune sera revealed a predominance of IgG anti-class I major histocompatibility complex (RT1) antibodies with a minor IgG fraction showing apparent endothelial cell specificity (non-RT1). This level of sensitization was associated with accelerated graft failure in 3 to 5 days from mixed humoral and cellular rejection. Sequential analysis of serial posttransplant graft biopsies revealed diffuse vascular IgG deposition and platelet thrombi in portal veins and periportal sinusoids within 3 minutes after reperfusion. This was followed by endothelial cell hypertrophy and vacuolization, periportal hepatocyte necrosis, arterial spasm, focal large bile duct necrosis, and hilar mast cell infiltration and degranulation. However, the liver allografts did not fail precipitously and hyperacute rejection was not seen. Kupffer cell phagocytosis of the sinusoidal platelets began as early as 30 minutes posttransplant and by 24 hours, the platelet thrombi had decreased. Cholangioles appeared focally at the edge of the limiting plates by 2 to 3 days, apparently in response to earlier periportal hepatocyte damage. A mononuclear portal and perivenular infiltrate became evident at 3 days, and graft failure was attributed to both antibody and cell-mediated rejection (Furuya et al: Preformed lymphocytotoxic antibodies: Hepatology 1992, 16: 1415-1422). The model described resembles observations in crossmatch positive human liver allograft recipients. The mechanisms of hepatic graft resistance to antibody mediated rejection and the possible long term consequences of early damage to the biliary tree are discussed. PMID- 8494043 TI - Monocyte adhesion and changes in endothelial cell number, morphology, and F-actin distribution elicited by low shear stress in vivo. AB - Left common carotid arteries of New Zealand white rabbits were ligated rostral to origin of the thyroid artery to reduce flow in the carotid upstream of this branch, and the vessels were examined 5 days later. Estimates of mean shear stress in the upstream carotid artery indicated a decrease of 73% (from 12.1 +/- 1.6 dynes/cm2 to 3.26 +/- 0.58 dynes/cm2). The contralateral common carotid artery carried collateral flow and experienced a 170% increase in shear stress (from 11.3 +/- 1.6 dynes/cm2 to 30.5 +/- 4.6 dynes/cm2). There was an adaptive reduction in the diameter in the left common carotid artery (low shear) from 2.07 +/- 0.06 mm to 1.75 +/- 0.12 mm, but the diameter of the right carotid was unchanged. Fluorescence microscopy and scanning electron microscopy of endothelium exposed to low shear revealed attachment of leukocytes (5.02 +/- 1.59 cells/mm2, mean +/- SE) that were identified as monocytes using the monoclonal antibody HAM 56. Laser confocal microscopy demonstrated that they were migrating across the endothelial cell monolayer. Fluorescence microscopy and scanning electron microscopy of left common carotid artery (low shear) also revealed cell morphology suggestive of endothelial cell desquamation. Endothelial cell loss was confirmed by morphometric determination of cell number (1.29 +/- 0.13 x 10(4) cells/mm length in experimental animals versus 1.71 +/- 0.08 x 10(4) cells/mm length in sham-operated animals). This endothelial cell loss may be an adaptation to a narrowing of carotid arteries exposed to low shear, which reduces luminal surface area of the vessel. Staining of F-actin with rhodamine phalloidin showed that endothelial cells exposed to low shear were less elongated and had fewer stress fibers than normal cells. By contrast, increasing shear stress by two- to threefold caused an increase in the number of stress fibers and a reduction in peripheral actin staining. Distal carotid ligation provided a consistent and well defined in vivo technique for manipulating shear stresses imposed on a large population of endothelial cells. PMID- 8494044 TI - Fibronectin biosynthesis and cell-surface expression by cardiac and non-cardiac endothelial cells. AB - We examined the biosynthesis and surface expression of fibronectin, an adhesive glycoprotein, in several types of cultured porcine endothelial cells: pulmonary artery, thoracic aorta, coronary artery, aortic valve, and mitral valve. We used immunocytochemical staining to compare the levels of fibronectin present in these same tissues in vivo. Using endogenous radiolabeling, we found that all cell types except aortic valve endothelial cells synthesized and released into the culture media substantial quantities of fibronectin. Using radioiodination of intact cells, we found that, whereas both thoracic aorta and pulmonary artery cells had measurable fibronectin on the surface, aortic valve, mitral valve, and coronary artery cells had little cell-surface fibronectin present. Immunocytochemical staining showed that all endothelial regions except aortic valve had substantial quantities of immunoreactive fibronectin in vivo. These data suggest that the aortic valve endothelium may be distinct from other endothelia. Such differences could be important for the pathogenesis of valvular disease. PMID- 8494045 TI - Inducible expression of MS-1 high-molecular-weight protein by endothelial cells of continuous origin and by dendritic cells/macrophages in vivo and in vitro. AB - Recently, we have described a monoclonal antibody, named MS-1, which identifies a novel high-molecular-weight protein expressed by noncontinuous, sinusoidal endothelia and by interstitial dendritic cells in certain normal human organs (S Goerdt, LJ Walsh, GF Murphy, JS Pober, J Cell Biol 1991, 113:1425-1437; and LJ Walsh, S Goerdt, JS Pober, H Sueki, GF Murphy, Lab Invest 1991, 65: 732-741). In this report, we demonstrate in studying a variety of skin lesions that MS-1 antigen can also be expressed by endothelia of continuous origin under certain pathological conditions. Among the skin lesions tested, MS-1 antigen expression by endothelial cells of continuous origin is frequently observed in wound healing tissue, in cutaneous T-cell lymphoma, in psoriasis, and in melanoma metastasis, ie, in 100%, 80%, 71%, and 71% of cases, respectively. In contrast, endothelial MS-1 antigen expression rarely occurred in other skin lesions, including vascular tumors, six of which were Kaposi's sarcomas (13% and 0% of cases with vascular MS 1 expression, respectively). The percentage of cases with MS-1+ vessels is only marginally different in malignant versus benign lesions (55% versus 31%); when melanocytic nevi, primary melanomas, and melanoma metastases are compared, however, an increase in the percentage of cases with MS-1+ vessels is seen (31%, 50%, and 71%, respectively). Apart from wound healing, the relative number of MS 1+ vessels in a given lesion amounts to less than 5% compared with the number of continuous type vessels stained by monoclonal antibody 1F10 (S Goerdt, F Steckel, K Schulze-Osthoff, H-H Hagemeier, E Macher, C Sorg, Exp Cell Biol 1989, 57: 185 192). In addition, the occurrence of MS-1+ vessels is not related to the overall vascularity of a given lesion. Thus, the conditions for MS-1 antigen expression by endothelia of continuous origin cannot as yet be exactly defined. Furthermore, we have noticed that the number of MS-1+ dendritic cells varies considerably in skin lesions; in the early patch lesions of Kaposi's sarcoma and in juvenile xanthogranuloma MS-1+ cells even constitute the major cell type. This prompted us to investigate MS-1 antigen expression and its regulation in cultured human monocytes/macrophages. Expression of MS-1 antigen by these cells regularly starts at day 3 of culture and reaches its maximal value at day 9, after which it declines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8494046 TI - Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms. AB - Inflammatory leukocytes play a central role in the pathogenesis of human atherosclerotic disease, from early atherogenesis to the late stages of atherosclerosis, such as aneurysm formation. We have shown previously that human abdominal aortic aneurysms are characterized by the presence of numerous chronic inflammatory cells throughout the vessel wall (Am J Pathol 1990, 137: 1199-1213). The signals that attract lymphocytes and monocytes into the aortic wall in aneurysmal disease remain to be precisely defined. We have studied the production of the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by aortic tissues obtained from 47 subjects. We compared the antigenic production of these cytokines by explants of: 1) human abdominal aneurysmal tissue, 2) occlusive (atherosclerotic) aortas, and 3) normal aortas. IL-8, which is chemotactic for neutrophils, lymphocytes, and endothelial cells was liberated in greater quantities by abdominal aortic aneurysms than by occlusive or normal aortas. Using immunohistochemistry, macrophages, and to a lesser degree endothelial cells, were found to be positive for the expression of antigenic IL-8. Similarly, MCP-1, a potent chemotactic cytokine for monocytes/macrophages, was released by explants from abdominal aortic aneurysms in greater quantities than by explants from occlusive or normal aortas. Using immunohistochemistry, the predominant MCP-1 antigen-positive cells were macrophages and to a lesser extent smooth muscle cells. Our results indicate that human abdominal aortic aneurysms produce IL-8 and MCP-1, both of which may serve to recruit additional inflammatory cells into the abdominal aortic wall, hence perpetuating the inflammatory reaction that may result in the pathology of vessel wall destruction and aortic aneurysm formation. PMID- 8494047 TI - Co-localization of aortic apolipoprotein B and chondroitin sulfate in an injury model of atherosclerosis. AB - In vitro, chondroitin sulfate (CS) proteoglycans (PGs) bind with high-affinity lipoproteins (LPs) containing apolipoprotein B (apo B), and cultured monocytes incubated with LP-PG complexes transform into foam cells (FCs). Consequently, arterial PGs are thought to contribute to the accumulation of LPs in atherosclerotic lesions, but their in vivo interaction has yet to be demonstrated. Balloon catheterization of rabbit aorta modifies the normal aortic distribution of endogenous LPs containing apo B, and determines their accumulation in normocholesterolemic conditions. The distribution of aortic CS PGs parallels that of apoB within the neointima of injured aortas and might contribute to a favorable environment for LP sequestration within the lesions. To visualize the in situ relationship between apo B and CS-PG, we performed experiments for double detection by immunofluorescence and by post-embedding electron microscope immunogold. The results indicated that the colocalization of endogenous LPs containing apo B and of the large intimal CS-PGs in advanced lesions developed under the regenerated endothelium. At the ultrastructural level, frequent associations were visualized in the extracellular space and in relation to FCs. The close spatial relation between CS-PG and apo B inside the aortic lesions seems to support the hypothesis of their in situ interaction and of a simultaneous cellular uptake, and may be related to the development of both extracellular lipid deposits and the formation of FCs in atherogenesis. PMID- 8494048 TI - Rickettsia australis infection: a murine model of a highly invasive vasculopathic rickettsiosis. AB - A mouse model of spotted fever group rickettsiosis, in which disease results from disseminated rickettsial infection of endothelial cells and vascular damage, was developed by intravenous inoculation of 6- to 8-week-old, male, Balb/c mice with Rickettsia australis. Animals developed progressively severe vasculitis, interstitial pneumonia, and multifocal hepatic necrosis. These lesions correlated with early disseminated infection of endothelial cells followed by growth and invasion of rickettsiae into perivascular cells. The dose of 2 x 10(6) organisms was uniformly lethal. Serum interleukin- (IL) 1, IL-6, and interferon (IFN) increased by day 3 and tumor necrosis factor (TNF) on day 5. TNF, IL-6, and IFN declined on day 7. Spleen cells responded to Rickettsia australis antigen by producing IFN, TNF, IL-1, and IL-6 on day 5, followed by lower quantities of these cytokines on day 7. Despite the production of antibodies, IFN, TNF, IL-1, and IL-6, a lethal outcome occurred frequently. A decreased ability to secrete IL 2 suggests an element of infection-associated immunosuppression. PMID- 8494049 TI - Platelet-activating factor: a mediator of pancreatic inflammation during cerulein hyperstimulation. AB - Hyperstimulation of the exocrine pancreas with cerulein causes acute pancreatitis, characterized by intensive interstitial edema, acinar vacuolization, leukocytic infiltration, and hyperamylasemia. Whereas the pathogenesis of cerulein-induced pancreatitis is not well-defined, a local inflammatory response may contribute to the full expression of acute pancreatitis. Platelet-activating factor (PAF) seems to be an important mediator of the inflammatory response. The present evidence includes: 1) pancreatic PAF levels increased in rats in which cerulein-induced pancreatitis was initiated, concomitant with an increase in calcium concentrations in the pancreatic tissue; 2) treatment of rats exposed to cerulein with WEB2170, a PAF receptor antagonist, was shown to reduce inflammatory injury, as demonstrated by decreases in pancreatic weight, Evan's blue extravasation, and myeloperoxidase activity and an improvement in pancreatic histology. In an idealized in vitro experiment mimicking cerulein-induced acute pancreatitis, in which pancreatic acini were employed, cerulein induced amylase release, an increase in [Ca2+]i, and an increase in PAF synthesis. Whereas amylase release was induced by low concentrations of cerulein (10(-11) mol/L), relatively high concentrations of cerulein (10(-9) mol/L) were required for the observed increases in PAF synthesis and the [Ca2+]i, indicating that these two responses may not occur under physiological conditions. The present study suggests that the pancreatic accumulation of PAF coupled with Ca2+ overload are important biochemical components of the pathophysiology of cerulein-induced acute pancreatitis. In fact, PAF production may serve as a primary mediator of inflammation observed during pancreatic hyperstimulation. This is an important observation that will allow a more detailed characterization of the molecular basis of cerulein-induced acute pancreatitis. PMID- 8494050 TI - Dystrophin deficiency is associated with myotendinous junction defects in prenecrotic and fully regenerated skeletal muscle. AB - The myotendinous junction (MTJ) is the major site of force transmission from myofibrils across the muscle cell membrane to the extracellular matrix. The MTJ is thus an appropriate model system in which to test the hypothesis that dystrophin, the gene product absent in Duchenne muscular dystrophy, functions as a structural link between the muscle cytoskeleton and the cell membrane. We studied changes in MTJ structure in dystrophin-deficient mdx mice during periods of growth and aging that spanned prenecrotic, necrotic, and regenerative phases of postnatal muscle development in mdx mice. Prenecrotic animals were found to exhibit structural defects at MTJs that were similar to those described previously in animals at the peak of necrosis, including a reduction in lateral associations between thin filaments and the MTJ membrane. These defects therefore occur before necrosis and may be directly related to the absence of dystrophin. Observations of regenerating and fully regenerated MTJs in adult animals show that the defects are still present, indicating that normal thin filament-membrane associations are never formed in dystrophin-deficient muscle. However, in prenecrotic as well as regenerated adult mdx muscle, the MTJ membrane is only slightly less folded than in age-matched controls. This indicates that mdx muscle possesses some dystrophin-independent mechanism that allows for the initial formation of MTJs, despite the absence of dystrophin. The presence of the defect in normal, lateral, thin filament-membrane associations in mdx muscle, regardless of age, supports the hypothesis that dystrophin functions as a structural link between thin filaments and the membrane. PMID- 8494051 TI - Pancreatic adenocarcinomas frequently show p53 gene mutations. AB - Thirty-four pancreatic adenocarcinomas were studied for the presence of p53 gene mutations by the single-strand conformation polymorphism method and by direct sequencing of PCR-amplified fragments. p53 protein expression was immunohistochemically evaluated using monoclonal PAb1801 and polyclonal CM1 antibodies. Mutations were detected in 14 cases. The transitions were six G to A and two A to G; the transversions were one C to G and two A to C; the remaining three were frameshift mutations. Immunostaining results were identical with both antibodies. Nuclear immunohistochemical p53-positive cells were found in nine p53 mutated cases and in 12 cases in which no mutation was detected. In most of these latter cases only a minority of cancer cells showed immunohistochemical positivity. Twenty-nine cases, including all p53 mutated cancers, were known to contain codon 12 Ki-ras gene mutations. Also in the light of the demonstrated cooperation of ras and p53 gene alterations in the transformation of cultured cells, our data suggest that p53 mutation is one of the genetic defects that may have a role in the pathogenesis of a proportion of pancreatic cancers. PMID- 8494052 TI - Lactotransferrin immunocytochemistry in Alzheimer and normal human brain. AB - Lactotransferrin (LF) expression was investigated immunocytochemically in postmortem brain tissues of normal controls and patients with Alzheimer's disease (AD). The antibody to LF stained some neurons weakly in young adult brains, but it stained many neurons as well as the glia of all types in elderly brains. LF expression was greatly up-regulated in both neurons and glia in affected AD tissue. It was very strongly associated with such extracellular pathological entities as diffuse and consolidated amyloid deposits and extracellular neurofibrillary tangles. In addition, it was identified in a minority of intracellular neurofibrillary tangles, neuropil threads, and degenerative neurites. LF is an iron scavenger and a complement inhibitor. Up-regulation may be a defense mechanism in AD-affected brain tissue. PMID- 8494053 TI - Hyperglycemic glucose concentrations up-regulate the expression of type VI collagen in vitro. Relevance to alterations of peripheral nerves in diabetes mellitus. AB - Electron microscopy of peripheral nerves obtained from two diabetic patients revealed large deposits of microfibrils and the presence of Luse bodies in the vicinity of perineurial cells. Microfibrils were found to accumulate also in the sciatic nerves of diabetic BB rats; these microfibrillar deposits were shown to contain type VI collagen by immunoelectron microscopy. Connective tissue cells cultured from rat sciatic nerves were exposed to high glucose concentrations. High glucose concentrations up-regulated the mRNA steady-state levels of alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains of type VI collagen and caused accumulation of type VI collagen-containing fibrils in the cultures. Immunostaining and in situ hybridizations demonstrated that perineurial cells, Schwann cells, and fibroblasts expressed type VI collagen at the mRNA and protein levels. The results suggest that the turnover and supramolecular assembly of type VI collagen are perturbed in diabetic nerves and that glucose per se increases the expression of type VI collagen in vitro. PMID- 8494054 TI - Genes of laminin B1 chain, alpha 1 (IV) chain of type IV collagen, and 72-kd type IV collagenase are mainly expressed by the stromal cells of lung carcinomas. AB - In this study, we analyzed the expression of messenger (m)RNAs for laminin B1 chain, alpha 1 (IV) chain of type IV collagen, and 72-kd type IV collagenase in 15 primary lung carcinomas and in two metastatic adenocarcinomas to the lung. The results show that the mRNA synthesis for these proteins mainly occurs in the stromal fibroblasts and endothelial cells. In a proportion of tumors, mRNAs for laminin B1 chain and 72-kd type IV collagenase could also be observed in carcinoma cells, but the amount of mRNAs was considerably lower in them than in the stromal cells. There were no convincing signals for the presence of the alpha 1 (IV) chain of type IV collagen mRNA in any of the carcinoma cells. A simultaneous expression or lack of expression of signals for laminin B1 chain and 72-kd type IV collagenase mRNAs could be observed in carcinoma cells of 12 cases, suggesting that the activation of these two genes may be somehow connected. There was no association between the mRNA expression and the differentiation degree or the size of the tumors. The occurrence of the mRNA synthesis for the 72-kd type IV collagenase in stromal fibroblasts and endothelial cells indicates that the stromal cells of tumors have a more pronounced impact on the spread of the neoplastic disease than previously thought. The results further show that in their ability to synthesize these proteins the stromal cells of tumors resemble those of developing embryonic tissues. This resemblance is probably connected with the constant remodeling of extracellular matrix in response to the proliferative activity of carcinoma cells. PMID- 8494055 TI - Immunogold localization of SP-A in lungs of infants dying from respiratory distress syndrome. AB - Prematurely born infants can develop the neonatal respiratory distress syndrome (RDS) because of a deficiency of pulmonary surfactant. This lipoprotein complex synthesized by type II pneumocytes has different ultrastructural forms--intra- and extracellular lamellar bodies, which within the alveoli are transformed into tubular myelin, and this in turn gives rise to the surface monolayer, the functionally active form of surfactant. We have previously shown that at autopsy RDS lungs lack tubular myelin and have decreased immunoreactivity for antisera to surfactant protein A (SP-A), an important component of tubular myelin. Therefore, we proposed a role for SP-A in the conversion of lamellar bodies to tubular myelin and in the pathogenesis of RDS. To explore this possibility further, we compared in 14 RDS and 14 control lungs the distribution of SP-A in ultrathin sections, using affinity-purified rabbit anti-human-SP-A IgG and goat anti-rabbit IgG-conjugated with 10 nm colloidal gold particles. In controls, gold label was present in lamellar bodies, endoplasmic reticulum, on the cytoplasmic membrane of type II cells, and on lamellar bodies and tubular myelin either within alveoli or macrophages. In RDS lungs, reduced label was present in the same intracellular compartments and organelles, except in tubular myelin, which is absent. It is postulated that if SP-A is indeed necessary for the conversion of lamellar bodies to tubular myelin, in RDS either there is a deficiency of adequate amounts of functional SP-A or some other important component of surfactant is missing. PMID- 8494056 TI - Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. AB - Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model. PMID- 8494057 TI - Comparative immunochemistry and ontogeny of two closely related coated pit proteins. The 280-kd target of teratogenic antibodies and the 330-kd target of nephritogenic antibodies. AB - We have previously shown that monoclonal antibodies specific for a 280-kd protein (gp280) concentrated within the coated pits of renal and yolk sac brush border induced fetal malformations, whereas antibodies specific for gp330, another coated pit protein with a similar distribution, had no deleterious effect on embryonic development. In this study, we show that gp280 and gp330 are closely related proteins, as indicated by: 1) similarities in peptide maps obtained after cyanogen bromide cleavage, 2) immunological cross-reactivity related to a minor contingent of antibodies that do not have teratogenic activity, and 3) asynchronous but related expressions during ontogenesis. During the early stages of development, the expression of the two glycoproteins was limited to (gp330) or predominant in (gp280) the clathrin-coated pits and intermicrovillar areas. In the pre-implantation embryo, gp330 was expressed by trophectodermal cells, which became negative in day-6 embryos trapped in endometrial infoldings. At this stage, gp280 and gp330 were both simultaneously detectable at the apical pole of the first entoblastic cells and remained expressed by the brush border of visceral yolk sac epithelial cells until the end of pregnancy. In addition, gp330 was expressed by amniotic cells and neurectodermal structures. During nephrogenesis, in contrast, the expression of gp280 and gp330 by the intermicrovillar areas of the proximal tubule cell was the result of a complex maturation process. gp280 and gp330 were diffusely distributed in S-shaped bodies in the presumptive areas of the glomerulus, proximal tubule, and distal tubule (gp330). During development of the nephron, the pattern of expression became progressively restricted to the proximal tubule and glomerulus (gp330), and selective localization in the intermicrovillar areas was only achieved in filtrating nephrons. PMID- 8494058 TI - Beta very low density lipoprotein and clathrin-coated vesicles co-localize to microvilli in pigeon monocyte-derived macrophages. AB - Macrophages derived from blood monocytes are key in the development of atherosclerosis, as monocyte migration into the intima and accumulation of cholesterol leads to foam cell formation. To investigate the relationship between lipoprotein binding and the distribution of clathrin-coated endocytic vesicles, monocyte-derived macrophages were exposed in vitro to beta very low density lipoprotein (beta VLDL), conjugated to colloidal gold, and later were processed for immuno-electron microscopy to localize clathrin-coated vesicles. The immunolocalization was done in conjunction with either cryosectioning or whole mount intermediate voltage electron microscopy. Preferential binding of beta VLDL on small membrane ruffles and microvilli was quantitatively verified. Clathrin coated vesicles were distributed throughout the cell; however, clusters of microvilli were associated with both a high concentration of coated vesicles and lipoprotein. Small membrane ruffles were not associated with clathrin-coated vesicles. These data support our hypothesis that endocytosis of beta VLDL near microvilli involves coated vesicles, whereas endocytosis of beta VLDL near ruffles is not mediated by coated endocytic vesicles. Furthermore, the association of coated vesicles with microvilli but not membrane ruffles may be important in understanding ligand trafficking within the cell. Given the distribution of coated vesicles within the cell, it is possible that the site of lipoprotein binding may determine the mechanism of entry into the cell and the metabolic effects of the internalized ligand. PMID- 8494059 TI - The Structured Interview for Sleep Disorders according to DSM-III-R. PMID- 8494060 TI - Test-retest reliability and validity of the Structured Interview for Sleep Disorders According to DSM-III-R. AB - OBJECTIVE: The purpose of this study was to evaluate the reliability of sleep disorder diagnoses in DSM-III-R by using a newly developed interview, the Structured Interview for Sleep Disorders According to DSM-III-R (SIS-D) and to evaluate the concordance between these diagnoses and sleep laboratory data. In addition, the sources of disagreements between two interviewers in the diagnoses given to the same patient were determined. METHOD: Two different interviewers used the SIS-D to diagnose 68 patients with complaints of sleep disorders. The concordance between these interviewers' diagnoses and polysomnographic findings was investigated by using kappa statistics. RESULTS: There were excellent reliabilities for almost all current main diagnostic categories and good concordance between diagnoses made on the basis of the structured interview and polysomnographic data. The main source of disagreement between interviewers was found in the symptom information given by the patient. CONCLUSIONS: These findings provide support for the utility of DSM-III-R sleep disorder diagnoses and for their retention in DSM-IV. These findings also accord well with a recent literature review of the DSM-III-R diagnosis of primary insomnia by the DSM-IV Work Group on Sleep Disorders. The good concordance between interview diagnoses and polysomnographic data suggests that a structured interview such as the SIS-D may be a useful screening instrument. The authors discuss the implications of these findings for the polysomnographic evaluation of chronic insomnia. PMID- 8494061 TI - Assessment of insight in psychosis. AB - OBJECTIVE: It is frequently reported that patients with psychotic disorders have poor insight into their illness. Previous research has suggested that poor insight may have considerable power in predicting the long-term course of chronic mental disorders and an impact on patients' compliance with treatment plans. The authors, proposing that insight is best viewed as a multidimensional phenomenon, developed the Scale to Assess Unawareness of Mental Disorder, which samples discrete and global aspects of insight across a variety of manifestations of illness. This article reports on a reliability and validity study of the scale. METHOD: The study subjects were 43 patients with schizophrenia and schizoaffective disorder. Various aspects of insight into illness were evaluated with the scale. In addition, ratings of psychopathology, course of illness, and compliance with treatment were made. RESULTS: Item variability was high and normally distributed, supporting the authors' contention that insight can be rated on a continuous rather than dichotomous scale. Results of the analyses examining the relations between the various dimensions of insight assessed and the psychopathology, course, and compliance variables were generally as hypothesized. Convergent validity with other global measures of insight was found, and aspects of poor insight were correlated with poorer compliance and course of illness. Examination of the interrelations among the four insight subscales revealed that these subscales sample independent phenomena. CONCLUSIONS: The Scale to Assess Unawareness of Mental Disorder has good reliability and validity and has certain advantages over previous measures of insight, suggesting the usefulness of a multidimensional view of this complex concept. PMID- 8494062 TI - The reliability of three definitions of bizarre delusions. AB - OBJECTIVE: This study was conducted to determine whether the interjudge reliability of the DSM-III-R concept of bizarre delusions could be improved by alternative definitions of the concept. METHOD: Twelve raters evaluated 180 delusions of separate psychiatric patients according to the DSM-III-R and two alternative definitions of bizarre delusions. RESULTS: The kappas for the DSM-III R definition and for one of the alternative definitions were 0.64 and 0.65, respectively; for the other alternative definition it was 0.45. All three definitions were highly intercorrelated, largely identifying the same cases. CONCLUSIONS: Neither of the alternative definitions of bizarre delusions was more reliable than the DSM-III-R definition. The reliability of the DSM-III-R definition, although only fair, is comparable to that of other important clinical concepts that play a major role in the DSM-III-R diagnostic criteria for psychotic disorders. PMID- 8494063 TI - The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. AB - OBJECTIVE: In an attempt to surmount the problem of retrospectively establishing the childhood diagnosis of attention deficit hyperactivity disorder, the authors constructed the 61-item Wender Utah Rating Scale (WURS) for adults to use to describe their own childhood behavior. In this paper they present their initial data collection and evaluation of the instrument's validity. METHOD: The scale was administered to 81 adult outpatients with attention deficit hyperactivity disorder, 100 "normal" adults, and 70 psychiatric adult outpatients with unipolar depression. The authors analyzed data from the 25 items of the scale that showed the greatest difference between the patients with attention deficit hyperactivity disorder and the normal comparison subjects and the relationship between the WURS and the patients' parents' judgment of childhood activity as measured by the Parents' Rating Scale. RESULTS: The patients with attention deficit hyperactivity disorder had significantly higher mean scores on all 25 items than did the two comparison groups. The difference between the mean total scores of the patients with attention deficit hyperactivity disorder and the normal subjects was also highly significant. A cutoff score of 46 or higher correctly identified 86% of the patients with attention deficit hyperactivity disorder, 99% of the normal subjects, and 81% of the depressed subjects. Correlations obtained between WURS scores and Parents' Rating Scale scores were moderate but impressive. The ability of WURS scores to predict response to methylphenidate replicated the authors' finding regarding the ability of Parents' Rating Scale scores to predict response to pemoline. CONCLUSIONS: The WURS is sensitive in identifying childhood attention deficit hyperactivity disorder and may be useful in recognizing attention deficit hyperactivity disorder in patients with ambiguous adult psychopathology. PMID- 8494064 TI - Evidence for the independent familial transmission of attention deficit hyperactivity disorder and learning disabilities: results from a family genetic study. AB - OBJECTIVE: The purpose of the study was to clarify the relationship between attention deficit hyperactivity disorder and learning disabilities. METHOD: The authors assessed learning disabilities in a sample of 140 children with attention deficit hyperactivity disorder and in 120 normal comparison children. They also assessed a sample of the probands' 822 first-degree relatives. RESULTS: The risk for learning disabilities was highest among relatives of probands with both attention deficit hyperactivity disorder and learning disabilities. The two disorders did not cosegregate in families. There was nonrandom mating between spouses with attention deficit hyperactivity disorder and learning disabilities. CONCLUSIONS: The two disorders are transmitted independently in families, and their co-occurrence may be due to nonrandom mating. Attention deficit hyperactivity disorder is likely to be etiologically independent from learning disabilities. PMID- 8494065 TI - Long-term affective and cognitive outcome in depressed older adults. AB - OBJECTIVE: The purpose of this naturalistic study was to examine the long-term (15 months and 4 years) cognitive and affective outcome following treatment with either cyclic antidepressants or ECT in depressed older adults. METHOD: Fifty five patients meeting criteria for major depression were rated as to cognitive impairment and were treated as clinically indicated with either a cyclic antidepressant or ECT. Long-term outcome was determined through psychometric retesting 15 months (N = 47) and approximately 4 years (N = 44) after treatment. RESULTS: Analysis of 15-month and 4-year outcome evaluations revealed that the majority of patients improved over time with respect to their depression, regardless of whether they exhibited pretreatment cognitive impairment or were treated with cyclic antidepressants or ECT. Fifteen months and 4 years after treatment, 72.3% and 83.7% of patients, respectively, exhibited clinically meaningful improvement. However, patients given both cyclic antidepressants and ECT demonstrated a relatively high rate of rehospitalization (50%) over the course of the 4 years. Except for patients who developed dementia, cognitive functioning remained stable or improved for the majority of patients. In patients who received ECT, those with normal pretreatment cognition had stable cognitive functioning over time and those who had pretreatment cognitive dysfunction showed improvement over the 4-year follow-up period. CONCLUSIONS: Results of this study indicate that the long-term prognosis of depression in older adults is generally favorable, although they may be prone to relapse and recurrence, which points to the need for rigorous monitoring and follow-up care. PMID- 8494066 TI - Bipolar II: the most common bipolar phenotype? AB - OBJECTIVE: The purpose of this study was to compare the pattern of affective psychopathology in families ascertained for genetic linkage studies through bipolar I probands to that in families ascertained through bipolar II probands. METHOD: All available first-degree relatives (N = 266) of 48 bipolar I and eight bipolar II probands were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version by one of two psychiatrists who had attained high interrater reliability for bipolar II disorder and other diagnoses. RESULTS: Bipolar II disorder was the most common affective disorder in both family sets. Forty percent of the 47 first-degree relatives of the bipolar II probands and 22% of the 219 first-degree relatives of the bipolar I probands were diagnosed with bipolar II disorder. On the other hand, only one bipolar I relative was found in the bipolar II families. CONCLUSIONS: Bipolar II disorder was the most prevalent affected phenotype in both bipolar I and bipolar II families and was the only expressed phenotype in half of the bipolar II families. This suggests that bipolar II disorder is genetically related to but less complex than bipolar I disorder. Accurate diagnosis of bipolar II disorder may be crucial in finding the genetic loci underlying bipolar disorders generally. PMID- 8494067 TI - Cardiovascular complications of ECT in depressed patients with cardiac disease. AB - OBJECTIVE: This study was conducted to determine the safety of electroconvulsive therapy (ECT) for depressed patients with serious cardiac disease. METHOD: The rate of complications in 40 patients with major depressive disorder and left ventricular impairment, ventricular arrhythmias, and/or conduction delay who received ECT was compared to the rate of complications in a matched comparison group of 40 depressed patients without cardiac disease who also received ECT. In addition, 21 of the patients with cardiac illness had received one or more inpatient trials of tricyclic antidepressants before receiving ECT, thereby permitting a comparison of cardiovascular complications of medication and ECT in the same patients. RESULTS: The patients with cardiac disease had a significantly higher rate of cardiac complications during ECT than did the comparison group without cardiac disease. The type of preexisting cardiac abnormality strongly predicted the type of cardiac complication that occurred during ECT. However, most of the complications were transitory and did not prevent the completion of ECT. Of the 21 patients with cardiac disease who had received tricyclic trials before ECT, 11 had been forced to discontinue drug treatment because of substantial cardiovascular side effects. In comparison, 38 of the 40 cardiac patients completed the course of ECT. CONCLUSIONS: With close monitoring for the development of arrhythmia and ischemic episodes, ECT can be given with relative safety to patients with severe cardiovascular disease. PMID- 8494068 TI - Depressive symptoms, medical illness, and functional status in depressed psychiatric inpatients. AB - OBJECTIVE: There is evidence that both psychiatric (especially affective) and medical illnesses contribute to physical disability. However, the differential contributions of specific psychiatric disorders and of medical pathology to functional status in psychiatric populations have not been studied. The authors therefore examined the contributions of depressive symptoms and medical illness to functional disability in depressed inpatients. METHOD: This prospective investigation included 109 psychiatric inpatients with DSM-III-R major depression. Regression techniques were used to examine the contribution of demographic variables (age, sex, education), depressive symptom severity (Hamilton Rating Scale for Depression score), psychiatric function (Global Assessment of Functioning Scale score), organ system pathology (Cumulative Illness Rating Scale score), and medical disability (Karnofsky Performance Status Scale score) to overall functional status (Instrumental Activities of Daily Living and Physical Self-Maintenance scores). These relationships were also examined in older and younger subgroups. RESULTS: Greater age, female sex, and illness factors all contributed to poorer functional status. Of the illness factors, psychiatric pathology contributed more to low functional status than did medical illness. The predictive power came specifically from the functionally based measures of psychiatric and medical illness; a quantitative measure of symptoms (Hamilton depression scale) or organ pathology (Cumulative Illness Rating Scale) did not significantly predict overall functional status. CONCLUSIONS: Clinicians and researchers should recognize that symptomatic and functional assessments tap related but different domains and that both psychiatric and medical illnesses contribute to overall disability. PMID- 8494069 TI - Secondary mania following traumatic brain injury. AB - OBJECTIVE: In this study patients were examined during the first year after traumatic brain injury to determine the presence of secondary mania. METHOD: A consecutive series of 66 patients with closed-head injury were evaluated in the hospital and at 3-, 6-, and 12-month follow-ups. The patients were examined with a semistructured psychiatric interview and scales for measurement of impairment in activities of daily living, intellectual function, and social functioning. Patients fulfilling the DSM-III-R criteria for mania were compared to patients with major depression and to patients without affective disturbances in regard to their background characteristics, impairment variables, and lesion locations. RESULTS: Six patients (9%) met the criteria for mania at some point during follow up. The presence of temporal basal polar lesions was significantly associated with secondary mania even when the effect of other lesion locations was taken into account. Secondary mania was not found to be associated with the severity of brain injury, degree of physical or cognitive impairment, level of social functioning, or previous family or personal history of psychiatric disorder. The duration of mania, however, appeared to be brief, lasting approximately 2 months. CONCLUSIONS: The 9% frequency of secondary mania in these patients with traumatic brain injury is significantly greater than that seen in other brain-injured populations (e.g., patients with stroke). The major correlate was the presence of a temporal basal polar lesion. PMID- 8494070 TI - Depression and neuropsychological performance in asymptomatic HIV infection. AB - OBJECTIVE: The authors examined the effect of depression on neuropsychological performance in HIV-infected men. Previous studies have suggested that depression may account for the neuropsychological abnormalities observed in some patients with HIV infection, but few studies have specifically examined this question. METHOD: An extensive neuropsychological test battery was administered to 121 HIV seropositive asymptomatic men and 42 HIV-seronegative comparison subjects. The seropositive subjects were grouped into depressed and non-depressed groups on the basis of scores on the Beck Depression Inventory, Hamilton Rating Scale for Depression, and Structured Clinical Interview for DSM-III-R. RESULTS: Statistical comparisons revealed very few measures on which the depressed seropositive subjects scored significantly worse than either of the nondepressed comparison groups. The nondepressed seropositive group differed consistently from the seronegative comparison subjects on measures of verbal memory and dexterity. CONCLUSIONS: These data indicate that the subtle neuropsychological abnormalities observed in some asymptomatic HIV-seropositive subjects cannot be attributed to depression. These data also indicate the advantages of a multifaceted approach to assessment of depression. PMID- 8494071 TI - Diagnostic comorbidity in persons with suicidal ideation and behavior. AB - OBJECTIVE: An initial finding of heightened risk of suicidal ideation or behavior among individuals in a random community sample who met diagnostic criteria for panic disorder or panic attacks was not replicated in later studies of both general and specific groups of psychiatric outpatients. The present study represented another effort to validate the finding. METHOD: The participants included 209 outpatients who had attempted suicide or were at high risk for continued suicidal behavior or eventual suicide. All subjects were evaluated with a structured clinical interview for assigning DSM-III-R diagnoses, the Modified Scale for Suicidal Ideation, the suicidal ideation subscale of the Suicide Probability Scale, and the Beck Hopelessness Scale. RESULTS: The findings indicated the relative complexity and importance of diagnostic comorbidity among these suicidal subjects. Mood disorders were the most frequent primary diagnoses, followed by phobias, posttraumatic stress disorder (PTSD), generalized anxiety disorder, and panic disorder. Panic disorder was not present as an isolated, independent diagnosis; on the contrary, all of the patients with panic disorder also received at least one additional comorbid diagnosis. Mean scores for suicidal ideation and hopelessness were greatest for patients with current comorbid primary mood disorder and panic disorder. However, a critical and equally important role was played by comorbid PTSD, generalized anxiety disorder, and phobias. CONCLUSIONS: The findings represent another failure to validate, with a specific clinical group, panic disorder as an independent risk factor for suicidal ideation or behavior. However, they highlight the possibility that panic disorder and other anxiety disorders are risk factors when they co-occur with a primary mood disorder. PMID- 8494072 TI - Mental disorders and comorbidity in suicide. AB - OBJECTIVE: The purpose of this study was to investigate the prevalence and comorbidity of current mental disorders defined by DSM-III-R among a random sample of suicide victims from a nationwide suicide population. METHOD: Using a psychological autopsy method, the authors collected comprehensive data on all suicide victims in Finland during 1 year. Retrospective axis I-III consensus diagnoses were assigned to 229 (172 male, 57 female) victims. RESULTS: One or more diagnoses on axis I were made for 93% of the victims. The most prevalent disorders were depressive disorders (59%) and alcohol dependence or abuse (43%). The prevalence of major depression was higher among females (46%) than among males (26%). Alcohol dependence was more common among the males (39% versus 18% for females). A diagnosis on axis II was made for 31% and at least one diagnosis on axis III for 46% of the cases. Only 12% of the victims received one axis I diagnosis without any comorbidity. CONCLUSIONS: The majority of suicide victims suffered from comorbid mental disorders. Comorbidity needs to be taken into account when analyzing the relationship between suicide and mental disorders and in planning treatment strategies for suicide prevention in clinical practice. PMID- 8494073 TI - Vulnerability to psychopathology in nicotine-dependent smokers: an epidemiologic study of young adults. AB - OBJECTIVE: In a previous article the authors reported associations between nicotine dependence and psychiatric disorders in a community sample of young adults. Increased lifetime rates of major depression and anxiety disorders were found in persons with DSM-III-R nicotine dependence but not in nondependent smokers. The purpose of the present study was to examine the associations of nicotine dependence with four measures of psychologic vulnerability to nonpsychotic psychiatric disorders. METHOD: A randomly chosen group of 1,007 21- to 30-year-old members of a large health maintenance organization were interviewed with the National Institute of Mental Health Diagnostic Interview Schedule, revised for DSM-III-R diagnoses. Self-ratings of neuroticism, negative affect, hopelessness, and general emotional distress were obtained. RESULTS: Nicotine dependence, but not nondependent smoking, was associated with higher scores on all four measures of vulnerability to psychopathology. With one exception the associations between nicotine dependence and these psychologic measures remained significant when the variables current smoking status, history of major depression or anxiety disorders, alcohol and drug use disorders, race, and level of education were controlled; the association of nicotine dependence with general emotional distress was not significant. CONCLUSIONS: Neuroticism and the correlated psychologic vulnerabilities may commonly predispose to nicotine dependence and major depression or anxiety disorders. PMID- 8494074 TI - An intervention to improve the reliability of manuscript reviews for the Journal of the American Academy of Child and Adolescent Psychiatry. AB - OBJECTIVE: The effects of methods used to improve the interrater reliability of reviewers' ratings of manuscripts submitted to the Journal of the American Academy of Child and Adolescent Psychiatry were studied. METHOD: Reviewers' ratings of consecutive manuscripts submitted over approximately 1 year were first analyzed; 296 pairs of ratings were studied. Intraclass correlations and confidence intervals for the correlations were computed for the two main ratings by which reviewers quantified the quality of the article: a 1-10 overall quality rating and a recommendation for acceptance or rejection with four possibilities along that continuum. Modifications were then introduced, including a multi-item rating scale and two training manuals to accompany it. Over the next year, 272 more articles were rated, and reliabilities were computed for the new scale and for the scales previously used. RESULTS: The intraclass correlation of the most reliable rating before the intervention was 0.27; the reliability of the new rating procedure was 0.43. The difference between these two was significant. The reliability for the new rating scale was in the fair to good range, and it became even better when the ratings of the two reviewers were averaged and the reliability stepped up by the Spearman-Brown formula. The new rating scale had excellent internal consistency and correlated highly with other quality ratings. CONCLUSIONS: The data confirm that the reliability of ratings of scientific articles may be improved by increasing the number of rating scale points, eliciting ratings of separate, concrete items rather than a global judgment, using training manuals, and averaging the scores of multiple reviewers. PMID- 8494075 TI - Images in psychiatry: Dorothea Dix. PMID- 8494076 TI - Adult reconstruction of childhood events in the multiple personality literature. AB - The author reviews the dependability of adult reports of childhood abuse and trauma, which are emerging in therapy with increasing frequency. He reviews the literature on multiple personality disorder to explore the extent to which corroboration of adult reports of childhood events is recorded. He also summarizes the relevant studies of memory both with and without the aid of hypnosis. He finds that there is minimal corroboration in the literature of the adults' reports of childhood abuse. Memories brought forth with the aid of hypnosis are undependable because of the large number of inaccuracies introduced by hypnotized subjects. Memories brought forth without hypnosis have been shown to be prone to distortion by intentional as well as by unwitting cues. The author concludes that the recent enthusiasm for the adult discovery of childhood abuse has been accompanied by little attention to factors that potentially affect recall of childhood abuse, including the bias of therapy. The use of hypnosis might well be an aggravating factor in distorted recollections of childhood abuse. Validation without corroboration by the therapist of the patient's memories has serious ethical and possibly legal consequences. PMID- 8494077 TI - The Tridimensional Personality Questionnaire in major depression. AB - The authors examined Tridimensional Personality Questionnaire scores in 40 patients with unipolar nonpsychotic major depression before and after antidepressant treatment. They found that scores on the novelty seeking and reward dependence dimensions were not affected by depressed state or by treatment response status. However, scores on the harm avoidance dimension were significantly lower in antidepressant responders and were altered by depressed state. PMID- 8494078 TI - Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity. AB - The growth hormone response to the acetylcholinesterase inhibitor pyridostigmine was measured in nine normothymic outpatients who met DSM-III-R criteria for obsessive-compulsive disorder. The responses were significantly elevated when compared to those found in a healthy comparison group (N = 9). The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder. PMID- 8494079 TI - Imipramine treatment of alcoholism with comorbid depression. AB - Of 60 depressed alcoholics who completed an open trial of imipramine, 27 (45%) responded with improvement in both mood and drinking behavior, and eight (13%) responded after further dosage increases or treatment with disulfiram. In a subsequent 6-month, randomized discontinuation trial, four of 13 subjects (31%) relapsed during imipramine treatment and seven of 10 (70%) relapsed while taking placebo. This suggests a potential treatment approach for a high-risk subgroup of alcoholics. PMID- 8494080 TI - Amount of calories retained after binge eating and vomiting. AB - While caloric consumption during binge eating has been measured, it is not known how many of the calories are retained in the gastrointestinal tract after vomiting. In 17 normal weight bulimic patients, there appeared to be a ceiling on the number of calories retained after vomiting. That is, whether or not bulimic patients had small (mean = 1,549 kcal, SD = 505) or large (mean = 3,530 kcal, SD = 438) binges, they retained similar amounts of kilocalories (mean = 1,128, SD = 497, versus mean = 1,209, SD = 574, respectively) after vomiting. PMID- 8494081 TI - Reliability of sexual risk behavior interviews with psychiatric patients. AB - Test-retest interviews examining recent sexual activity were administered to 27 severely ill psychiatric patients after stabilization. Three reports were judged to be questionable. For the 16 sexually active patients among the remaining 24, high test-retest reliability was found for number of sexual partners, frequency of episodes, and proportions of episodes involving vaginal intercourse and use of condoms. The interviews did not exacerbate psychiatric symptoms. PMID- 8494082 TI - Fluoxetine and onset of its therapeutic effect. PMID- 8494083 TI - Vaginal anesthesia associated with fluoxetine use. PMID- 8494084 TI - Maintenance ECT for treatment of recurrent mania. PMID- 8494085 TI - Toxic hepatitis by clozapine treatment. PMID- 8494086 TI - Clozapine in a bipolar depressed patient. PMID- 8494087 TI - Case report of probable sertraline-induced akathisia. PMID- 8494088 TI - Depression among elderly African Americans and Mexican Americans. PMID- 8494089 TI - Hysterical conversion, organic pathology, and DSM-IV. PMID- 8494090 TI - Psychiatry in eastern Europe. PMID- 8494091 TI - Homelessness and the mentally ill. PMID- 8494092 TI - Homelessness and the mentally ill. PMID- 8494093 TI - Peer relationships in early childhood socialization. PMID- 8494094 TI - Cross-cultural studies in tardive dyskinesia. PMID- 8494095 TI - Vitamin E treatment of tardive dyskinesia. PMID- 8494096 TI - Vitamin E treatment of tardive dyskinesia. PMID- 8494097 TI - Hysterectomy in patients with panic disorder: a failure to replicate. PMID- 8494098 TI - The locus ceruleus and anxiety disorders in demented and nondemented familial parkinsonism. PMID- 8494099 TI - Refine bizarre delusion criterion. PMID- 8494100 TI - PTSD and substance abuse. PMID- 8494101 TI - Kaposiform hemangioendothelioma of infancy and childhood. An aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. AB - We report the clinical and pathological features of nine distinctive, but relatively unknown, vascular tumors of infancy and childhood presenting as soft tissue masses often associated with locally aggressive disease, lymphangiomatosis and Kasabach-Merritt syndrome. The patients, four males and five females, were all in their first decade of life except for two (median, 2 years; range, 5 months to 19 years). These tumors involved deep soft tissues of the upper extremity (four cases), retroperitoneum (two cases), chest wall, scalp, and neck (one case each). Four patients also had Kasabach-Merritt syndrome, and three patients had lymphangiomatosis. Lymphangiomatosis consisted of diffusely infiltrating lymphangioma of soft tissue (three cases) and in two by the additional presence of bone lesions. In one of these three cases, lymphangiomatosis antedated the diagnosis of the vascular tumor, and in the remainder they were concurrently diagnosed. Tumors were characterized by infiltrating, interconnecting sheets or irregular nodules of slender endothelial cells lining crescentic or slit-like vessels and, less commonly, rounded capillary-type vessels. Within some tumors, nests of epithelioid endothelial cells with prominent eosinophilic cytoplasm containing finely granular hemosiderin, hyaline droplets, and cytoplasmic vacuoles were identified. Smaller amounts of hemosiderin were observed within the spindled endothelial cells and microthrombi could be seen occasionally within the tiny lumina. Nuclear atypia was minimal within these tumors and mitotic figures were infrequent, averaging 2 to 3/10 high-power fields (HPF) (range 0-7/10 HPF). Larger, well-formed feeding vessels were present at the periphery of the tumor. The endothelium of these vessels expressed factor VIII-AG, CD34, and bound Ulex europaeus, and contained an occasional perithelial cell expressing muscle-specific actin. In contrast, the spindled tumor cells expressed only CD34. Human papilloma virus (HPV)-16-like DNA transcripts, which have been identified in cases of Kaposi's sarcoma, were not detected by polymerase chain reaction in two cases. Follow-up information revealed that four patients were alive without disease after wide excision, multiple excision(s), or amputation (one case); three were alive with disease; and two died, one from lymphangiomatosis with respiratory compromise and the other from hemorrhage complicating Kasabach-Merritt syndrome. It appears that treatment should consist of wide local excision and supportive therapy for associated symptoms. PMID- 8494102 TI - Lymphangiomatosis. Histologic and immunohistochemical analysis of four cases. AB - Lymphangiomatosis is a rare condition that involves bone, soft tissue, or viscera in a diffuse fashion. We report four examples affecting male infants and boys (aged 9 months to 11 years: mean, 5.3 years). All four cases presented with respiratory symptoms. Investigations showed chylothorax in all patients and chylopericardium in one patient. Three patients showed multiple lytic lesions in several bones on the x-rays. Imaging studies of lungs and spleen suggested lymphangiomatosis. Biopsy specimens of the parietal pleura, lung, skin, or bone revealed an increase in the size and number of thin-walled channels lined by attenuated endothelial lining. All had histological evidence of parietal pleural involvement. In addition, lung involvement was seen in three cases and skin involvement in two cases. Factor VIII-related antigen and CD31 were the most reliable immunocytochemical markers in highlighting the endothelia. All the patients had repeated thoracocentesis and pleurodesis to control chylothorax; three died within 6 to 33 months of presentation (mean, 15 months). Autopsy performed in two cases revealed additional involvement of spleen, bone, and mediastinum. Further, lymphangiectasia was seen in the liver, kidney, tests, lymph node, intestines, and adrenals. PMID- 8494103 TI - Relationship between perineural tumor invasion on needle biopsy and radical prostatectomy capsular penetration in clinical stage B adenocarcinoma of the prostate. AB - We studied 302 needle biopsies for perineural invasion for sensitivity and specificity in predicting capsular penetration in subsequent radical prostatectomies. Perineural invasion was seen in 20% of needle biopsies, with a sensitivity of 27% and a specificity of 96% in predicting capsular penetration. By including tumor with a Gleason sum of 7 or greater or perineural invasion on needle biopsy as being predictive, sensitivity increased to 36% with a specificity of 94%. By restricting perineural invasion to cases with more than one nerve involved or a nerve involvement of a diameter 0.1 mm or greater, specificity increased to 97% and 99%, respectively, with sensitivity falling to 15% and 9%, respectively. Measuring perineural invasion on needle biopsy helps to identify capsular penetration and may help in planning nerve-sparing radical prostatectomy in the decision of whether to sacrifice part or all of the neurovascular bundle on the side of the biopsy. PMID- 8494104 TI - Carcinosarcoma of the prostate. AB - Carcinosarcoma of the prostate is a biphasic tumor containing adenocarcinoma (ACA) and recognizable sarcomatous components. It is a rare neoplasm with only 12 previous reported cases. We describe three additional cases arising between 4 and 6 years after initial diagnosis of prostatic ACA. Two patients were initially treated by prostatectomy, pelvic external beam radiotherapy, and hormonal manipulation. The third patient was treated by pelvic lymphadenectomy and 125I implants. After the development of the sarcomatous component, the first two are still alive with distant metastases and residual pelvic disease at 9 and 17 months. The third patient died with disease 7 months after diagnosis. Histologically, prostatic ACA was recognized in all three cases, as well as a neoplastic mesenchymal component that appeared later. Foci of osteosarcomatous, chondrosarcomatous, and myosarcomatous differentiation were recognized in two of the three cases. Based on the chronologic and the histologic evolution of the neoplasm, we favor sarcomatoid transformation of the ACA as the most likely histogenesis. It appears that radiotherapy and hormonal therapy may be important in the development of at least some of these tumors. PMID- 8494105 TI - Coexistence of nodular lymphocyte predominance Hodgkin's disease and Hodgkin's disease of the usual type. AB - Recent literature suggests that usual Hodgkin's disease (nodular sclerosing and mixed cellularity types or UHD) and nodular lymphocyte predominance Hodgkin's disease (NLPHD) may be distinct clinical and pathologic entities. Thus, coexistence of NLPHD and UHD in the same patient is expected to be rare. We undertook a review of cases accessioned as NLPHD and UHD in the Laboratory of Surgical Pathology at Stanford University Hospital between January 1980 and May 1992 and found five patients with UHD that predated, followed, or coexisted with lesions histologically typical of NLPHD. All of the patients were male with ages ranging from 10 to 30 years at presentation (median, 22 years; mean, 22.2 years). The sites initially involved by disease were primarily peripheral lymph nodes in the region of the head and neck: cervical (three), supraclavicular (one), submandibular (one). One patient presented with mixed-cellularity Hodgkin's disease (MCHD), two with nodular sclerosis Hodgkin's disease including the cellular phase, one with NLPHD, and the remaining patient presented with a composite malignancy comprising MCHD and NLPHD. Development of the second lymphoma was associated with a somewhat more variable distribution of nodal involvement. The morphologic features in each biopsy specimen resembled either typical NLPHD or UHD, except for one case in which cells with features of both Reed-Sternberg cells and lymphocytic and histiocytes cells were identified. However, the immunophenotypic profiles obtained with a panel of monoclonal antibodies remained distinct for all cases studied. None of the cases showed reactivity with antibodies against the Epstein-Barr-virus latent membrane protein. Thus, NLPHD and UHD maintain a distinct phenotype, even when occurring in the same patient. A second conclusion is that the utility of Leu-7 (CD57) reactivity in distinguishing NLPHD applies to problematic as well as classic cases. Finally, Epstein-Barr virus is not implicated in NLPHD cases associated with UHD. PMID- 8494106 TI - Osteogenic melanoma. A rare variant of malignant melanoma. AB - Osteogenic melanoma is a rare variant of malignant melanoma; only eight cases have been reported. To characterize this unusual neoplasm further, we present four new cases. Two patients were men and two were women (average age, 56 years; range, 47-78 years). All tumors arose from acral lentiginous melanomas. Three were subungual finger lesions and one was on the sole of the foot. All four had been previously diagnosed as or were suspected to have been primary osseous lesions. The vertical growth components were high-grade, amelanotic sarcomatoid malignancies with abundant osteoid matrix. Two tumors also had chondroblastic differentiation. Cells with epithelioid features, including prominent eosinophilic nucleoli, were discernible in every tumor. Regional lymph node metastases in two cases retained osteocartilaginous differentiation, whereas metastatic cells in another case were purely epithelioid. Tumor cells in every case were immunoreactive for S-100 protein and vimentin, and non-reactive for cytokeratin. Two tumors also expressed HMB-45. Melanosomes were identified ultrastructurally in every tumor. Follow-up information was available on every patient. Three developed regional lymph node metastases and are currently alive and well after 14, 39, and 101 months. The fourth patient died of metastatic uterine carcinoma 20 months postoperatively. The differential diagnosis of osteogenic melanoma includes osteosarcoma as well as atypical fibro-osseous proliferations. Clinico-pathologic features that support a diagnosis of osteogenic melanoma include junctional activity, absence of primary bony involvement, regional nodal metastases, immunoreactivity for S-100 protein and/or HMB-45, lack of cytokeratin reactivity, and ultrastructural identification of melanosomes. PMID- 8494107 TI - Pure squamous cell carcinoma of the larynx with cervical nodal metastasis showing rhabdomyosarcomatous differentiation. Clinical, pathologic, and immunohistochemical study of a unique example of divergent differentiation. AB - We describe a unique case of pure squamous carcinoma of the larynx that developed a cervical lymph node metastasis showing rhabdomyosarcoma admixed with squamous carcinoma (that is, carcinosarcoma). The rhabdomyosarcoma showed foci immunoreactive to multiple cytokeratin monoclonal antibodies, as well as to markers for striated muscle, thus indicating true divergent epithelial and rhabdomyosarcomatous differentiation. Although the morphogenesis of carcinosarcomas remains controversial, the sequence of events for the current case favors sarcomatous transformation of the original carcinoma (that is, sarcomatous neometaplasia of the primary carcinoma clone). The possible contributory role of radiation therapy in this case in inducing such a change is noted. PMID- 8494108 TI - Vulvar angiomyofibroblastoma. PMID- 8494109 TI - Multiparametric image cytometry of nevi and melanomas. AB - Multiparametric image cytometry was applied to 10 examples each of malignant melanoma and common, Spitz, and dysplastic nevus. DNA index, area, and 21 parameters describing chromatin texture were measured for 50 nuclei in each lesion. Linear discriminant analysis was used to derive discriminant functions based on the measured parameters. The analysis demonstrated that chromatin texture provides more diagnostic information than either DNA index or nuclear area. The discriminant functions allowed 68% of nuclei to be accurately classified among the four groups, and allowed 37 of the 40 lesions to be accurately classified as nevus or melanoma. PMID- 8494110 TI - Granulomas associated with tetanus toxoid immunization. AB - Two patients developed localized nodular reactions at the site of prior tetanus toxoid injections. Histology of the lesions showed granuloma formation with central granular debris surrounded by a histiocytic mantle. Peripheral to this was a dense lymphoid infiltrate with eosinophils. Examination with energy dispersive x-ray microanalysis confirmed the presence of aluminium and phosphorus in the granular debris but not in the surrounding infiltrate. PMID- 8494111 TI - The polymerase chain reaction. Method and applications in dermatopathology. AB - Since it was first reported in 1985, the polymerase chain reaction (PCR) has revolutionized the way molecular studies are performed, and has developed into one of the most powerful tools in molecular pathology. By use of a cyclic change of temperature, a specific and exponential in vitro amplification of a target DNA sequence can be achieved within hours. As a template for PCR reactions, total genomic DNA is used; this can be readily extracted from clinical specimens. Very low quantities of DNA, as well as DNA degraded by fixation, can also be used as a template for PCR reactions, allowing formalin-fixed, paraffin-embedded tissue to become amenable to detailed molecular analysis. Sequences specific for certain viruses and other microorganisms, as well as molecular marker sequences associated with various types of human cancer, can be readily detected in paraffin-embedded tissue sections. The methodology of PCR, along with various applications in dermatopathology, are reviewed. PMID- 8494112 TI - Structure of the dermis in type VIIC Ehlers-Danlos syndrome. AB - This report is the first to study histological, immunopathological, ultrastructural, and morphometric aspects of the abnormal structure of the dermis in Ehlers-Danlos syndrome, type VIIc. This disease, resulting from a defect in procollagen peptidase, resembles dermatosparaxis in animals. Dermal cells were abnormal in many aspects, including their large number, their strong argent affinity, and the occasional presence of oligocilia. Factor XIIIa-positive dendrocytes were, however, few in number. The stroma had many tears resulting from the absence of collagen bundles replaced by a loose meshwork of cauliflower fibrils. The mean collagen area, measured from fibrils, was similar to normal, and the individual values of this parameter were inversely related to the form factor that quantifies irregularity in fibril shape. Basement membranes were also defective, with an apparent paucity or focal absence of type IV collagen and laminin. The biology responsible for these many alterations in dermal structure is complex and not yet understood. The many morphological changes seen in Ehlers Danlos syndrome, type VIIc, underscore the complexity of cell-matrix interactions in establishing a normal dermis. PMID- 8494113 TI - Mast cells in human ulcers. AB - The distributions of mast cells in decubitus, venous stasis, and arteriosclerotic human skin ulcers were studied. Mast cells were found primarily in the papillary dermis but were also numerous in the reticular dermis of the three types of ulcers. There were mast cells inside the epidermis and many more in granulation tissue. Intraepidermal mast cells were more numerous in venous stasis ulcers than in decubitus or arteriosclerotic ulcers. Many of the mast cells in these areas appeared to be intact. There were also some free and intracellular granules that stained like those in mast cells, in necrotic and granulation tissue. These findings raise questions about the role of mast cells in the epidermis and in necrosis and repair of skin ulcers. PMID- 8494114 TI - Clear cell sarcoma of tendons and aponeuroses and malignant blue nevus arising in prepubescent children. Report of two cases and review of the literature. AB - The low incidence of malignant melanoma in children makes the diagnosis of this disease problematic for clinicians and pathologists. The diagnosis becomes especially difficult when the melanoma is a rare variant of conventional melanoma, such as clear cell sarcoma of tendons and aponeuroses (CCSTA), and malignant blue nevus (MBN). In this report we describe two prepubescent children, one with a MBN, and one with CCSTA. The patient with MBN also developed acute lymphoblastic leukemia, and died of metastatic malignant melanoma within 1 year of diagnosis. We present the histological and clinical features of these cases and review the literature on these rare tumors arising in prepubescent children. PMID- 8494115 TI - Cutaneous acanthamoeba infection associated with leukocytoclastic vasculitis in an AIDS patient. AB - Cutaneous Acanthamoeba infection is a rare complication of immunocompromised individuals including those having acquired immunodeficiency syndrome (AIDS), who often have concurrent central nervous system involvement. Acanthamoeba typically involves the skin and central nervous system by disseminating from a primary focus in the lungs or sinuses. We report an unusual patient with AIDS who developed cutaneous infection with Acanthamoeba, apparently without CNS infection but with sinus involvement. Histologically, the purpuric lesions showed prominent leukocytoclastic vasculitis as well as myriads of organisms. PMID- 8494116 TI - Papillary eccrine adenoma. A case report with immunohistochemical examination. AB - The case of a 52-year-old woman with papillary eccrine adenoma is reported. The lesion presented clinically as a slowly growing nodule on the dorsum of the left foot. Histopathologically, the tumor was composed of multiple, dilated tubular structures lined by two or more layers of epithelial cells. The inner cell layer formed intraluminal papillary projections in some of the tubules. Most of the lumina were filled by eosinophilic granular material. Immunohistochemical examinations that use the avidin-biotin method showed immunoreactivity to S-100 protein, carcinoembryonic antigen, and epithelial membrane antigen. These findings support the hypothesis that papillary eccrine adenoma differentiate toward the secretory epithelium of sweat glands. PMID- 8494117 TI - Agminate blue nevus combined with lentigo. A variant of speckled lentiginous nevus? AB - We report a case of agminate blue nevus combined with a lentigo patch in a 38 year-old woman. The combination was interpreted as a unique and peculiar variant of speckled lentiginous nevus. PMID- 8494118 TI - Clear cells of eccrine glands in a patient with clear cell syringoma associated with diabetes mellitus. AB - We report a patient who presented with clear cell syringomata concomitant with diabetes mellitus. Also prominent were increased numbers of clear cells within the eccrine glands. This observation of increased numbers of clear cells in eccrine glands of diabetic patients may represent another skin finding that is related to diabetes mellitus. PMID- 8494119 TI - Dilated pore nevus. A histologic variant of nevus comedonicus. AB - Histology of a nevus comedonicus showed aggregates of dilated follicular cysts reminiscent of dilated pore of Winer. This finding has not been previously reported. We propose the term dilated pore nevus for this lesion, which we conceive to be a histologic variant of nevus comedonicus, similar to porokeratotic eccrine ostial and dermal duct nevus. PMID- 8494120 TI - Condyloma acuminatum with superficial spirochetosis simulating condyloma latum. AB - We report a case of a 12-year-old boy with a large perianal condyloma. The lesion was found to contain both spirochetes (Warthin-Starry stain) and human papillomavirus types 6 or 11 (in situ hybridization). Because of persistent negative serologies for syphilis and lack of other clinical stigmata of syphilis, the lesion was diagnosed as condyloma acuminatum with secondary involvement by spirochetes of probable intestinal origin. The case demonstrates the potential histologic similarities between condyloma latum and condyloma acuminatum, as well as the pitfalls of using the Warthin-Starry stain to establish the diagnosis of secondary syphilis. PMID- 8494121 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 6. PMID- 8494122 TI - Epenthesis from A to Z. PMID- 8494123 TI - Another case of focal acantholytic dyskeratosis of the anal canal. PMID- 8494124 TI - DNA determination in dysplastic nevi. A comparative study between flow cytometry and image analysis. AB - Dysplastic nevi (DN), described in 1978, have been associated with increased risk of melanoma, but the role of DN as precursors of melanoma is still controversial. Recent studies have shown that DN are very common in the general population, bringing into question this purported association. Numerous investigations have attempted to correlate the presence of DN in individuals with specific phenotypic and genotypic features, including the presence of abnormal DNA content. Because the occurrence of such abnormal DNA stemlines in neoplasms may be associated with malignant behavior, we studied 38 biopsies from 19 patients that histologically fulfilled criteria for DN in order to ascertain characteristics of DNA content. Nuclear suspensions made from paraffin-embedded tissue were evaluated by both flow cytometry and image analysis techniques. All cases demonstrated diploid populations by both DNA measurement methods. Our results contradict previous reports of aneuploid populations in these melanocytic lesions. PMID- 8494125 TI - Where now? The anaesthetist's development in management. PMID- 8494126 TI - Dose-response for analgesic effect of amitriptyline in chronic pain. AB - A randomised, double-blind, multiple dose, crossover study with three 3-week treatment periods was set up to compare the analgesic efficacy and adverse effects of amitriptyline in oral doses of 25, 50 or 75 mg. Patients used diaries to assess their pain, and clinic assessments were made at the end of each treatment period. It was found that in 29 patients with chronic (more than 2 months) pain, amitriptyline 75 mg provided significantly greater efficacy than amitriptyline 25 or 50 mg. There was no significant difference in mood scores between the different doses of amitriptyline, but sleep was judged significantly better with 75 mg compared with 25 mg. The incidence of adverse effects was significantly higher with the 75 mg dose, and the principal adverse effects were dry mouth and drowsiness. In the context of chronic pain, the analgesic effect of amitriptyline was shown to have a dose-response unrelated to mood elevation, but there was a dose-response for the incidence of adverse effects. PMID- 8494127 TI - Interaction of H2-receptor antagonists and benzodiazepine sedation. A double blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam. AB - H2-receptor antagonists differentially inhibit cytochrome P450 and this may affect the rate at which benzodiazepines are metabolised. However, it is not known whether this delayed clearance results in prolonged psychomotor impairment. In a randomised double-blind trial 28 healthy volunteers received two single doses of midazolam (0.07 mg.kg-1) at an interval of one week during which they took cimetidine 400 mg, ranitidine 150 mg or placebo, each twice daily. Recovery from the benzodiazepine was monitored on each occasion over a 12 h period using a battery of psychometric tests. There was wide individual variation in performance; however, an overall measure of impairment indicated a significant difference at 2.5 h (p < 0.05), the cimetidine group having a high impairment score. This decrement appeared to be in cognitive and psychomotor functions and was not reflected in the subjective assessment. PMID- 8494128 TI - The effect of cardiopulmonary bypass on cholinesterase activity. AB - Cholinesterase activity was determined in 18 patients who had undergone either hypothermic (n = 9) or normothermic (n = 9) cardiopulmonary bypass. The anaesthetic technique was standardised to avoid agents known to affect cholinesterase. Activity was determined in blood samples taken before the induction of anaesthesia, during cardiopulmonary bypass and for at least 7 days postoperatively. In six patients cholinesterase activity was also measured at 6 weeks postoperatively. All the patients were of normal cholinesterase genotype. In both groups cholinesterase activity fell by approximately 60% coinciding with the start of cardiopulmonary bypass, from a mean of 5976 to 2636 IU.l-1 in the hypothermic group, and from 5901 to 2615 IU.l-1 in the normothermic group (p < 0.001 in both instances) (normal range 4300-10,500 IU.l-1). Cholinesterase activity remained at this reduced level for at least 7 days postoperatively. By 6 weeks, activity had returned to within 7% of pre-induction values. There were no differences in cholinesterase activity between the hypothermic and normothermic groups at any of the sampling times. PMID- 8494129 TI - Topical nitroglycerin prevents the pressor response to tracheal intubation and sternotomy in patients undergoing coronary artery bypass graft surgery. AB - Thirty adult patients who underwent coronary artery bypass graft surgery were allocated randomly to one of two equal groups to receive either 2% nitroglycerin, or a placebo ointment, applied topically over an area of 5 cm by 10 cm, in a double-blind manner, 1 h before induction of anaesthesia. Premedication consisted of oral diazepam 5-10 mg, intramuscular morphine 0.2 mg.kg-1 and promethazine 0.4 mg.kg-1. Anaesthesia was induced with morphine 0.15-0.2 mg.kg-1 and thiopentone 3 5 mg.kg-1. Laryngoscopy and tracheal intubation were facilitated by suxamethonium 1.5 mg.kg-1, and pancuronium 0.1 mg.kg-1 was used for subsequent muscle relaxation. Anaesthesia was maintained with 0.5% halothane and 40% oxygen in nitrous oxide. A significant increase in blood pressure occurred during and after laryngoscopy and tracheal intubation, and following midline sternotomy in the control group. These changes were absent in patients pretreated with topical nitroglycerin. The nitroglycerin group also maintained a lower rate-pressure product than the control group. We conclude that topical nitroglycerin is a simple and useful pretreatment to prevent the pressor response to tracheal intubation and midline sternotomy in patients undergoing coronary artery bypass graft surgery. PMID- 8494130 TI - Leg elevation and wrapping in the prevention of hypotension following spinal anaesthesia for elective caesarean section. AB - Ninety-seven parturients undergoing elective Caesarean section were allocated randomly to have their legs elevated to approximately 30 degrees on pillows or elevated and wrapped with elasticated Esmarch bandages or neither (controls) following spinal anaesthesia. All patients received intravenous crystalloid (20 ml.kg-1 over 20 min) prior to spinal injection and were placed in the left lateral tilt position. Significant hypotension was treated with intravenous ephedrine in 5 mg bolus doses. Leg wrapping resulted in a significant reduction in the incidence of postspinal hypotension in comparison to the control group (18% compared to 53%, p = 0.004). This represents a five-fold reduction in the likelihood of postspinal hypotension (odds ratio 5.3, 95% CI 1.7-16.3). Leg elevation alone did not significantly reduce the incidence of hypotension (39%). There was no significant difference in the time of onset of hypotension between the groups. For those patients requiring ephedrine, there was no significant difference in mean dose requirements between the groups. The use of leg compression immediately postspinal provides a simple means of reducing the accompanying hypotension and should be used more widely. PMID- 8494131 TI - Ventilatory effects of pneumoperitoneum monitored with continuous spirometry. AB - Inspiratory and expiratory tidal volume, peak and plateau airway pressure, compliance of the respiratory system, pressure-volume and flow-volume loops were monitored continuously and recorded in seven women undergoing laparoscopy with carbon dioxide insufflation to an intra-abdominal pressure of 1.6 kPa. All patients were anaesthetised using a total intravenous technique and a constant minute ventilation was maintained. Peak airway and plateau airway pressures increased by 50% and 81% respectively, whilst the compliance of the respiratory system decreased by 47% during the period of increased intra-abdominal pressure. Following release of the pneumoperitoneum, peak and plateau pressures remained elevated by 37% and 27% respectively, and the compliance was 86% of the pre insufflation value. On-line monitoring of respiratory volumes, pressures and compliance may be helpful during general anaesthesia for laparoscopic procedures to avoid the potential harmful effects of increased airway pressures occurring with increased intra-abdominal pressure. PMID- 8494132 TI - The measurement of right ventricular ejection fraction by thermodilution. A comparison of values obtained using differing injectate ports. AB - Thermodilution measurements of cardiac output and right ventricular ejection fraction were obtained using a rapid response pulmonary artery catheter. Values were compared when injectate was administered via either a cannula within the right internal jugular vein or the dedicated right atrial port of the pulmonary artery catheter. Mean (SD) bias for cardiac output and right ventricular ejection fraction measurements were 0.08 (0.32) l.min-1 and 2.6 (6.6)% respectively. We therefore conclude that both injectate techniques will provide similar values for cardiac output but dissimilar values for right ventricular ejection fraction measurement. PMID- 8494133 TI - Interpleural analgesia and phrenic nerve paralysis. AB - A case of phrenic nerve paralysis following interpleural analgesia for cholecystectomy is reported. The pre-operative chest X ray was normal but chest X ray after cholecystectomy and interpleural analgesia revealed a raised right hemidiaphragm. This resolved after discontinuation of the interpleural analgesia and was probably a result of phrenic nerve paralysis produced by the interpleural local anaesthetic. PMID- 8494134 TI - Delayed cutaneous fluid leak from the puncture hole after removal of an epidural catheter. AB - A case of a delayed but persistent cutaneous fluid leak from a puncture hole following removal of an epidural catheter is presented. The fluid was subsequently found not to be cerebrospinal but interstitial oedema fluid. This case demonstrates the importance of performing simple investigations on any such fluid before ordering more complex tests. PMID- 8494135 TI - The 'SiteRite' ultrasound machine--an aid to internal jugular vein cannulation. AB - The 'SiteRite' is a portable ultrasound imaging system designed to aid vein location during internal jugular vein cannulation. It was compared to the use of anatomical landmarks for internal jugular vein cannulation. It was easy to use and gave good quality images, increased the speed of cannulation, decreased the number of attempts to locate the internal jugular vein and reduced the failure rate, although it had no effect on the incidence of carotid artery puncture. PMID- 8494136 TI - The Miller tracheal cuff pressure control valve. Clinical use in controlled and spontaneous ventilation. AB - A constant pressure differential valve for the control of tracheal tube cuff pressure was tested under clinical conditions. Fifty-one patients underwent controlled ventilation and 20 patients were allowed to breathe spontaneously. Nitrous oxide 66% with oxygen 33% and halothane were used via a circle system. With controlled respiration at a fresh gas flow of 3-10 l.min-1, the expiratory cuff pressures of 10.1-16 cmH2O and the inspiratory cuff pressures of 23.4-32.4 cmH2O were below venous and arterial mucosal capillary perfusion pressures respectively. Cuff pressures were unaltered with time. Methylene blue instilled into the larynx did not appear in the trachea. Fifty-two control patients had the same incidence of sore throat (40%) and hoarseness (30%) at 24 h. With spontaneous ventilation, fresh gas flows of 5-15 l.min-1 maintained the cuff pressure above 10 cmH2O. We conclude that this valve prevents excessive tracheal cuff pressure while maintaining the airway seal. PMID- 8494137 TI - Epidural tramadol for postoperative pain relief. AB - The efficacy of epidurally administered tramadol hydrochloride, a weak centrally acting analgesic, was studied for the relief of postoperative pain. Sixty patients undergoing abdominal surgery were randomly allocated to three treatment groups to be given the following agents by the epidural route: group 1 tramadol 50 mg; group 2 tramadol 100 mg; group 3 10 ml of bupivacaine 0.25%. The drugs were administered at the patients' request with each patient being allowed four doses in the first 24 h following surgery. Blood pressure, pulse rate, respiratory rate, arterial blood gas analyses, pain scores, the interval between doses and the occurrence of any side effects were recorded. Pain scores (assessed using a visual analogue scale) were significantly less (p < 0.05) at 3, 12, and 24 h in patients receiving tramadol 100 mg than in those receiving tramadol 50 mg or bupivacaine. The mean interval between doses for groups 1, 2 and 3 was 7.40 h, 9.36 h and 5.98 h respectively. The mean interval in group 2 was significantly longer than in group 3 (p < 0.05). The incidence of nausea and vomiting in group 2 was significantly higher than in group 3 (p < 0.05). PMID- 8494138 TI - The effect of low dose aspirin on bleeding times. AB - This double-blind, controlled study assessed the effect of low-dose aspirin on bleeding times. Thirty patients, in the last trimester of their first pregnancy, who were also taking part in a trial to evaluate the effect of low-dose aspirin on the development and progress of pregnancy-induced hypertension, had their bleeding times measured using the Simplate 11 Bleeding Device. Our study showed there was no significant difference between the bleeding times of the two groups and all measurements fell within the normal range. PMID- 8494139 TI - Continuous subarachnoid infusion of local anaesthetic. AB - We observed the sensory, motor and cardiovascular changes occurring during subarachnoid infusion of bupivacaine 0.125% at 15 ml.h-1 in six patients. After 1 h, motor block and lower sensory levels were consistent and predictable but upper sensory levels were variable. There was a moderate decrease in systolic blood pressure. Regular assessments of motor block are more likely to detect accidental subarachnoid infusion than assessments of upper sensory level or measurements of blood pressure. PMID- 8494140 TI - A comparison of percutaneous and perconjunctival routes of administration of peri ocular anaesthesia for day case cataract surgery. AB - This study of 100 day case patients having cataract surgery under local anaesthesia compared patient acceptance of two peri-ocular techniques; a transcutaneous method and a transconjunctival method. A significant difference was found in relation to the pain felt on injection such that all peri-ocular blocks at our unit are now done via the perconjunctival route. PMID- 8494142 TI - Training anaesthetists--the use of 'floaters'. PMID- 8494141 TI - Anaesthetists' attitudes to parental presence at induction of general anaesthesia in children. AB - Attitudes of anaesthetists of various grades working in different types of hospital in England and Wales, to parental presence in the anaesthetic room during induction of anaesthesia in children were assessed by means of a postal questionnaire. Of the 300 questionnaires sent out, 244 (82%) were completed. The majority of anaesthetists were in favour of parental presence in the anaesthetic room for induction of anaesthesia in children over the age of 1 year undergoing routine day case surgery. A small but significant number expressed reservations about some aspects of parental presence. The grade of anaesthetist and type of hospital did not appear to influence the response. PMID- 8494143 TI - Procedures undertaken by medical students. PMID- 8494144 TI - Too many sharps. PMID- 8494145 TI - The Riyadh Intensive Care Programme. PMID- 8494146 TI - An analogue approach to audit in anaesthesia. PMID- 8494147 TI - Mallampati classification and laryngeal mask airway insertion. PMID- 8494148 TI - Unexpected cause of tracheal cuff failure. PMID- 8494149 TI - A problem with Portex 8.5 mm tracheal connectors. PMID- 8494150 TI - Delivery of excess volatile agent due to a vaporizer fault. PMID- 8494151 TI - Local anaesthesia and venous cannulation. PMID- 8494152 TI - The laryngeal mask airway and training in nasotracheal intubation. PMID- 8494153 TI - Placement of a Cook airway exchange catheter via the laryngeal mask airway. PMID- 8494154 TI - Use of the laryngeal mask airway in neonatal resuscitation. PMID- 8494155 TI - Aspects of safety in anaesthesia. PMID- 8494156 TI - Hypertensive response to passage of a nasogastric tube. PMID- 8494157 TI - When the chips are down--the laryngeal mask in anger. PMID- 8494158 TI - 'That chap on the PCAS is a bit twitchy today'. PMID- 8494159 TI - Mounting problems. PMID- 8494160 TI - Nil by mouth after midnight. PMID- 8494161 TI - Hoarseness and sore throat after tracheal intubation. Small tubes prevent. PMID- 8494162 TI - Hypotension from the interaction of ACE inhibitors with stable plasma protein solution. PMID- 8494163 TI - Safety in reserve. PMID- 8494164 TI - Rapid presentation of the Guillain-Barre syndrome. PMID- 8494165 TI - Postoperative hoarseness. PMID- 8494166 TI - Nasotracheal intubation causing a nasopharyngeal mass. PMID- 8494167 TI - Difficult intubation in paediatric palatoplasty. PMID- 8494168 TI - Catecholamine response to laryngoscopy and intubation: on the importance of sampling site. PMID- 8494169 TI - Laser surgery of the larynx using a metal insufflation catheter for ventilation of the lungs. PMID- 8494170 TI - Prevention of possible accidental facial injuries caused by tracheal tube connectors. PMID- 8494171 TI - Quantitative microdialysis under transient conditions. AB - A microdialysis method is described which allows for the quantitative determination of extracellular analyte concentration under transient conditions. The method provides the extracellular concentration and the in vivo probe recovery as a function of time. The technique is based on the method for steady state conditions but differs in the use of a between-group rather than a within group design. Following cocaine and amphetamine administration, a significantly greater increase in extracellular DA was found than was estimated from the dialysate using conventional microdialysis methods. The discrepancy is due to microdialysis probe recovery decreasing concurrently with the increase observed in extracellular DA following cocaine and amphetamine injections. The method estimates the extracellular concentration independently of any changes in recovery. PMID- 8494172 TI - Miniaturized flexible amperometric lactate probe. AB - A flexible lactate electrode was made of 400 +/- 100 7-micron-diameter carbon fibers, epoxy embedded in a 0.3-mm-diameter polyimide tubing. The electrode was modified by precipitating on it the relatively insoluble complex formed between 1100 kDa partially N-ethylamine quaternized poly[(vinylpyridine) Os(bipyridine)2Cl]Cl (POs-EA) and lactate oxidase. The steady-state lactate electrooxidation current, at 2 mM lactate concentration and at 22 degrees C, was 400 nA. The 50 +/- 10 microAc cm-2 current density and the 20 mA cm-2 M-1 sensitivity decreased only by 5% when the partial pressure of oxygen was increased from 0.0 to 0.2 atm. The electrode retains its sensitivity after dry storage at 4 degrees C for 4 months in air but loses half of its sensitivity in 7 h at 37 degrees C through polymer desorption when operated at 0.4 V (SCE). To eliminate interference by species that are electrooxidized at 0.4 V (SCE), the lactate-sensing probe was (a) electrically insulated with an epoxy made of poly(vinylimidazole) cross-linked with ethylene glycol diglycidyl ether and (b) coated with an immobilized horseradish peroxidase (HRP)/glucose oxidase (GOX) film. The latter film was formed by coimmobilizing the two enzymes through periodate oxidation of their oligosaccharides to aldehydes and forming Schiff bases between the polyaldehydes and the enzymes' lysyl amines. In the presence of 1 mM glucose and in air, the interfering electrooxidation of 0.1 mM ascorbate was reduced by a factor of 20. This reduction results from formation of hydrogen peroxide in the glucose-catalyzed reaction and H2O2 oxidation of the ascorbate in a reaction catalyzed by HRP. PMID- 8494173 TI - Novel instrumentation and biomedical applications of very near infrared fluorescence. AB - A high wavelength fluorescent probe, Nile Red, was added to four proteins, viz., bovine albumin, alpha 1-acid glycoprotein, beta-lactoglobulin and ovomucoid. Nile Red showed an enhancement in fluorescence and a shift in emission wavelength, suggesting it was bonding hydrophobically to these proteins. Drug displacement of Nile Red from alpha 1-acid glycoprotein was achieved with both D,L-propranolol and flufenamic acid, showing that the binding site is less electrostatic and more hydrophobic in nature. In order to monitor these interactions, a simple spectrofluorimeter was constructed from solid-state components; the sensitivity of this instrument compared well with that of standard laboratory spectrofluorimeters. PMID- 8494174 TI - Development of an antibody-based amperometric biosensor to study the reaction of 7-hydroxycoumarin with its specific antibody. AB - An amperometric biosensor, based on an anti-7-hydroxycoumarin (7-OH-coumarin) antibody immobilized at the surface of a glassy carbon electrode, and contained behind a cellulose dialysis membrane, is described. The electrochemical behaviour of this metabolite at the bare glassy carbon electrode was found to be well defined by using differential-pulse voltammetry, and a 90% decrease in peak height was observed on binding of the antibody to the antigen, which occurs at the electroactive site of 7-OH-coumarin. The kinetics of the antibody-antigen reaction was investigated and a first-order reaction was observed with k = 0.0329 mA min-1. This system provides a novel method for studying antibody specificity and the kinetics of such antibody-antigen interactions. PMID- 8494175 TI - Effective laboratory monitoring for the abuse of the beta-agonist clenbuterol in cattle. AB - The use of the beta-agonist clenbuterol (CBL) as a growth promoter has been outlawed in European meat production. The detection of its illegal use is dependent on CBL residues persisting in animal tissues for longer than the withdrawal times given by abusers. A comparison of urine, bile and liver matrices indicated that analysis of the liver offered the best possibility for CBL detection. However, an experimental study showed that CBL detection following withdrawal could be further extended (up to 56 d) if the retina was used as the target tissue. Analysis of 703 retina and liver samples from cattle suspected of CBL medication revealed that 96 cattle had CBL residues present in their retinas, only 46 of these were liver positive. There were no instances of liver CBL residues being detected without the associated retina also being positive. PMID- 8494176 TI - White House meeting focuses on women's health issues. PMID- 8494177 TI - Education models epitomize innovation. PMID- 8494178 TI - Adapting education for the future. PMID- 8494179 TI - Safe medication practices entail education of family, patients. PMID- 8494180 TI - AIDS wallet cards help in patient education. PMID- 8494181 TI - Reform discussions include ANA input. PMID- 8494182 TI - From classroom to clinicals, student nurse is on the go. PMID- 8494183 TI - Rewards of teaching to student understanding. Interview by Roberta Olson. PMID- 8494185 TI - Quality is goal of CE accreditation. PMID- 8494184 TI - Continuing education critical to nursing's place in a reformed system. PMID- 8494186 TI - The role of critical care in managed competition. PMID- 8494187 TI - Workshop explores nursing's role in managed care, managed competition. PMID- 8494188 TI - ANA to help develop managed care curriculum. PMID- 8494189 TI - Groups call attention to violence against health care workers. PMID- 8494190 TI - Clarification on AIDS definition. PMID- 8494191 TI - Are nurses ready to share a vision? PMID- 8494193 TI - The transformation of education. PMID- 8494192 TI - Nursing education for tomorrow's nurse. PMID- 8494194 TI - Airway disease update. PMID- 8494195 TI - Medical chronobiology: concepts and applications. AB - Chronobiology is the study of biologic rhythms and biologic time structure. Medical chronobiology, in particular, is concerned with circadian (24-h) and other bioperiodic influences on human diseases such as (1) their occurrence or variation in severity over the 24-h or other time scale, (2) response of patients to diagnostic procedures and tests and, (3) the effect of medical treatments. The symptoms of chronic diseases--allergic rhinitis, regular and variant type angina, rheumatoid and osteoarthritis, asthma, epilepsy, hypertension and ulcer disease, for example, commonly exhibit circadian, menstrual cycle (in women), and seasonal patterns. The life-threatening events of myocardial and cerebral infarction and cerebral hemorrhage also exhibit predictable-in-time patterns over 24 h and the year. In the clinic, bioperiodicities strongly influence the results of blood pressure assessment, cutaneous antigen testing and spirometric evaluation, to mention but a few. Bodily rhythms also affect the pharmacokinetics and dynamics of medications. A major goal of medical chronobiology is chronotherapeutics, the optimization of pharmacotherapies, taking into consideration rhythm-dependencies in the kinetics and dynamics of medications plus predictable-in-time variability in the manifestation and severity of human disease. The concepts of medical chronobiology are discussed in detail herein. Examples have been chosen for their relevance to clinical allergy and chest medicine. PMID- 8494196 TI - Mechanism of airway inflammation in asthma. AB - Airway inflammation has emerged as an important contributor to mechanisms of asthma. Furthermore, the presence of airway inflammation is present even in the absence of severe symptoms. To study the mechanisms by which bronchial inflammation can occur in asthma, a number of models have been developed including the airway response to antigen in allergic subjects. The pattern that has emerged from such studies indicates prompt pulmonary mast-cell activation and the apparent initiation of an inflammatory response. This inflammatory response develops over hours and is important in the later and more persistent development of bronchial obstruction. The eosinophil is an important cell in this process as are proinflammatory cytokines generated from activated lung mononuclear cells. The consequence of this multiple cell, multiple proinflammatory product interaction is the establishment of a self-perpetuating, redundant process by which asthma severity increases. PMID- 8494197 TI - Nocturnal asthma: circadian rhythms and therapeutic interventions. AB - The pathophysiology of nocturnal asthma is closely associated with chronobiology, the science of biologic processes that have time-related rhythms. The 24-h cycle (circadian rhythm) is especially important in understanding the changes in pulmonary function that occur in sleeping asthmatics. Nocturnal asthma can be seen as representing an exaggerated amplitude of normal circadian patterns, including increased airway responsiveness and decreased lung function at night and in the early morning. Circadian changes in epinephrine, AMP, histamine and other inflammatory mediators, cortisol, vagal tone, body temperature, and lower airway secretions are potential mechanisms that favor nocturnal bronchoconstriction. Circadian variation in pulmonary function, as well as the effect of therapeutic interventions, can be readily demonstrated by having patients record peak expiratory flow rate values at different times of the day and night, using a peak flow meter. The treatment of nocturnal asthma requires a chronopharmacologic approach, in which more intense therapy is targeted to coincide with the time that the disease is the worst. Chronopharmacology includes the strategic use of longer-acting beta-agonists, theophylline, corticosteroids, and anticholinergics. Understanding the kinetics of the different drug preparations is necessary for most effective timing of dose. Future treatment of nocturnal asthma will continue to be guided by increased understanding of circadian and sleep-related events. PMID- 8494198 TI - Current issues in the use of theophylline. AB - Theophylline is a safe and effective medication for the management of chronic asthma. It reduces nocturnal bronchospasm and airways hyperresponsiveness, and its addition to effective doses of beta-agonists and corticosteroids leads to further improvement in symptom control. These properties are the result of actions other than simple bronchodilation, and there is a strong possibility that anti-inflammatory activity accounts for its clinical advantages. Serious side effects are uncommon and their rate can be further reduced through appropriate precautions. Recent studies have alleviated the concern over cognitive and behavioral side effects in children. PMID- 8494199 TI - Review of the clinical efficacy of theophylline in the treatment of chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Therapeutic options are few and are often limited in efficacy. Theophylline is one option, but its use appears to have recently reached a threshold point of deemphasis. Given the consequences of further diminishing the available treatment of COPD, a reappraisal of theophylline's role is imperative. This report reviews the clinical efficacy of theophylline in managing patients with COPD. Special consideration is given to theophylline's effects on pulmonary function (i.e., bronchodilation, exercise capacity, and gas exchange), dyspnea, mucociliary clearance, respiratory muscle performance, cardiovascular function, and neuroinspiratory drive. Despite the lack of standardization in study design and methodology among the studies evaluating theophylline, the conflicting results, and the questions that remain to be answered, evidence indicates that theophylline can provide meaningful therapeutic benefit to patients with COPD. In addition, several studies in patients with COPD have shown that theophylline and inhaled beta-agonists interact in an additive fashion, and the combination therapy results in additional objective and subjective improvement over that achieved by either preparation alone. PMID- 8494200 TI - Establishment of quality control procedures in clinical flow cytometry. PMID- 8494201 TI - Disregulation of leukocyte glutathione in AIDS. PMID- 8494202 TI - Characterization of T lymphocyte subset alterations by flow cytometry in HIV disease. PMID- 8494203 TI - Flow cytometry in the transplant laboratory. PMID- 8494204 TI - Qualitative versus quantitative immunophenotyping. PMID- 8494205 TI - Trends and developments in flow cytometry instrumentation. PMID- 8494206 TI - Fluorescence spectral overlap compensation for any number of flow cytometry parameters. PMID- 8494207 TI - PE-CY5. A new fluorescent antibody label for three-color flow cytometry with a single laser. PMID- 8494208 TI - Molecular cytogenetic analysis of human tumors. PMID- 8494209 TI - Reimbursement for clinical flow cytometry testing. AB - Throughout the United States, reimbursement for new laboratory technology is not well understood by the clinicians and laboratory personnel who provide it. It is important to understand how new technology will be paid for in today's changing, more tightly controlled, health-care funding environment. For flow cytometry testing, specifically, this confusion is not just restricted to providers of the tests. The carriers from many states still list flow cytometry as "investigational", contrary to the 1988 HCFA ruling. Although the HCFA ruling is not subject to interpretation by state Medicare carriers, it is often up to the provider whose claims are being denied to educate the carrier concerning its mistake. When confronted with the appropriate evidence (sometimes including a phone call from the regional HCFA office), most carriers relent. It is critical to note that claims must be billed correctly. This means that approved ICD-9-CM codes must be used with the appropriate CPT-4 codes. If there is no prevailing rate established in the state or if it has been established prohibitively low, it will be necessary to lobby and educate the carrier in regard to the medical necessity of the testing, as well as justifying the cost. This can be done by providing the medical director of the carrier with all necessary patient information, laboratory reports, and scientific literature validating the use of the technology for each individual claim. It may also require submitting cost justification data supporting the request. The importance of the development of a good working relationship with one's local Medicare carrier cannot be overemphasized. This relationship is a critical component of establishing a fair and appropriate rate for the reimbursement of any test. PMID- 8494210 TI - Fluorescence in situ hybridization in leukemia. Applications in diagnosis, subclassification, and monitoring the response to therapy. PMID- 8494211 TI - Potential clinical applications of signal transduction measurements in marrow transplantation and HIV-1 infection. PMID- 8494212 TI - White cell and thrombocyte disorders. Standardized, self-learning flow cytometric list mode data classification with the CLASSIF1 program system. PMID- 8494213 TI - Introduction to functional cell assays. PMID- 8494214 TI - CD45 gating for routine flow cytometric analysis of human bone marrow specimens. PMID- 8494215 TI - Flow cytometric reticulocyte analysis and the reticulocyte maturity index. AB - Reticulocyte analysis has evolved to one of the accepted and routinely practiced clinical applications of flow cytometry technology. Similar to CD4 measurements, FCM technology has contributed to documented improvements in reticulocyte counting precision over previous microscope-based techniques. The ability to FCM instruments to quantitate fluorescence intensity has been utilized to derive a parameter of reticulocyte maturity, which we have termed the reticulocyte maturity index. The FCM-derived RMI parameter offers an additional perspective to assess the erythropoietic response in anemic patients over reticulocyte counting alone and provides further insight into the differential diagnosis of anemia. Clinical utility of the RMI has been reported in monitoring expensive, new technology therapies, such as bone marrow transplantation and erythropoietin therapy. FCM reticulocyte analysis is still not fully mature, but is in a state of continued evolution. Needs exist for (i) improved software for data analysis, (ii) newer automation techniques to improve interlaboratory correlations, and (iii) further validation and refinement of the reticulocyte maturity index parameter. PMID- 8494216 TI - Flow cytometric measurement of platelet function and reticulated platelets. PMID- 8494217 TI - Flow cytometric analysis of lymphomas and acute leukemias. AB - In summary, flow cytometry is highly applicable to the detection and classification of leukemias and lymphomas due to the ease with which single-cell suspensions may be made. Composite immunophenotypic analysis is essential for classifying leukemias once the disease is detected by traditional means. In contrast, in the detection of lymphoproliferative diseases, the composite immunophenotype is itself diagnostic of the disease process. Characterization of size, as measured by light scatter and by DNA ploidy and cell cycle analysis, contributes to the further subdivision of lymphoproliferative disorders. Specifically, small, monoclonal cells that are diploid with a synthetic fraction of 5% are characteristic of low-grade lymphomas. Admixtures of large and small cells wherein the large cells are monoclonal and the small cells are either monoclonal or heterogeneous may be seen in intermediate lymphomas. In this category, DNA ploidy is variable and the total synthetic fraction is usually between 5% and 15%. High-grade lymphomas, with the exception of the immunoblastic category, are usually of intermediate size, are diploid or near-diploid, and exhibit synthetic fractions greater than 15%. Interestingly, few reactive T cells are seen. Ongoing efforts to standardize procedures will eventually result in more widespread applicability together with improved understanding of the attributes and limitations of this technology. The most important consideration, however, is that the technology is useless in the absence of a working knowledge of the biology of the diseases to be characterized. Conversely, the complexity of flow cytometry is sufficient to warrant rigorous training of laboratory professionals in this field. PMID- 8494218 TI - Integrating flow cytometry in the hematology laboratory. A curmudgeon's view. PMID- 8494219 TI - Altered sensitivity of DNA in situ to denaturation in apoptotic cells. PMID- 8494220 TI - Prognostic significance of S-phase fraction as measured by DNA flow cytometry in gynecologic malignancies. PMID- 8494221 TI - Analysis of lymphomas by flow cytometry. Current and emerging strategies. AB - The standard style for reporting results of immunophenotype analysis of lymphocytes by FCM is in the form of percentages of antigen-expressing cells. This procedure does not fully exploit the capabilities of FCM and is not always applicable to neoplastic samples. An alternative procedure for data analysis consists of a visual examination of the graphical displays of antibody binding patterns and size distribution without considering the actual fraction of fluorescent (positive) cells. Although it requires visual training and detailed examination of the data, this "pattern recognition" strategy offers unique diagnostic information that cannot be derived from simple percentages. Furthermore, the use of multiple labels, combined with interactive gating based on changes in cell size or intensity of antigen expression, provides high levels of sensitivity in detection of neoplastic cells and is an invaluable strategy in cases of minimal tumor involvement. PMID- 8494222 TI - Applicability of flow cytometry in breast cancer. AB - The cumulative evidence indicates that flow cytometry can provide important information about the behavior of breast tumors. A particularly appealing aspect of this technology is the ability to determine flow cytometric parameters on fresh surgical samples, frozen biopsy specimens, and archival paraffin-embedded blocks. However, several issues regarding the standardization of tissue preparation and the cell cycle analyses must be addressed before flow cytometry can be routinely applied on a wide scale. Quality control standards are currently being discussed that will help to reduce interlaboratory variability, particularly with respect to absolute values of S-phase fraction. PMID- 8494223 TI - Characterization of aneuploid cell culture lines by DNA index. Survey of Lombardi Cancer Research Center laboratories. PMID- 8494224 TI - A novel dye that facilitates three-color analysis of PBMC by flow cytometry. PMID- 8494225 TI - HLA-B27 typing. A comparative evaluation between the standard NIH method and flow cytometry. PMID- 8494226 TI - Clinical utility of a lymph node normal range obtained by flow cytometry. PMID- 8494227 TI - A semiautomated whole blood lysis method for measuring surface immunoglobulin on peripheral blood lymphocytes. PMID- 8494228 TI - Immunophenotyping of pediatric bone marrow. Preliminary report of normal reference ranges. PMID- 8494229 TI - Quality control in immunophenotyping. Use of human CD4+ and CD8+ T clones as standards. PMID- 8494230 TI - The use of lyophilized human cells as antigenic controls for flow cytometry measurements. PMID- 8494231 TI - Decrease in CD8+ lymphocytes in atopic dermatitis is associated with a preferential loss of cytotoxic effector cells rather than suppressor inducer cells. PMID- 8494232 TI - A rapid whole blood lysis technique for the diagnosis of moderate or severe leukocyte adhesion deficiency (LAD). PMID- 8494233 TI - Assessment of interlaboratory variability of immunophenotyping. Results of the College of American Pathologists Flow Cytometry Survey. PMID- 8494234 TI - Analysis of prostate cancer by flow cytometry and correlation with Gleason scores. PMID- 8494235 TI - Influence of HIV-1 infection and cigarette smoking on leukocyte profile in homosexual men. PMID- 8494236 TI - Penicillin inhibits agonist-induced expression of platelet surface membrane glycoproteins. PMID- 8494237 TI - Effect of time, temperature, and anticoagulant on flow cytometry and hematological values. PMID- 8494238 TI - Flow cytometric applications of the new fluorochrome RED670. PMID- 8494239 TI - Depletion of infiltrating leukocytes and identification of normal fibroblasts prior to the proliferative assessment of rare event tumor cells. PMID- 8494240 TI - Correlative patterns between cellular DNA content, N-myc oncogene amplification, and karyotypic abnormalities in human neuroblastomas. A preliminary report. PMID- 8494241 TI - Human macrophage (M phi) polymorphism demonstrated by differential phagocytosis of fluorescent polystyrene beads. PMID- 8494242 TI - Circulating lymphocyte subsets after total lymphoid irradiation in chronic progressive multiple sclerosis. PMID- 8494243 TI - Lymphocyte immunophenotyping with extended quantitative analysis of list-mode files for epidemiologic health studies. PMID- 8494244 TI - Flow analysis of embryonal carcinoma and normal testicular tissue. PMID- 8494245 TI - NIAID Division of AIDS flow cytometry quality assessment program. PMID- 8494246 TI - Improved precision in the enumeration of absolute numbers of lymphocyte phenotypes with long-term monthly proficiency testing. PMID- 8494247 TI - Quality control issues in DNA content flow cytometry. PMID- 8494248 TI - Quality control and quality assurance in flow cytometry. PMID- 8494249 TI - The clinical utility of DNA cytometry. PMID- 8494250 TI - Distribution and function of lymphocyte surface antigens. Molecules costimulating T lymphocyte activation and effector function. PMID- 8494251 TI - Immunological monitoring utilizing novel probes. PMID- 8494252 TI - Nutritional aspects of embryonic CNS development: in vitro and animal studies. Introduction to Part I. PMID- 8494253 TI - Folic acid and neural tube defects. Introduction to Part II. PMID- 8494254 TI - Folic acid and the prevention of neural tube defects. PMID- 8494255 TI - Epidemiologic associations of multivitamin supplementation and occurrence of neural tube defects. PMID- 8494256 TI - Effects of recent research on recommendations for periconceptional folate supplement use. PMID- 8494257 TI - Maternal folate status and the risk for neural tube defects. The role of dietary folate. PMID- 8494258 TI - Interactions between environmental, genetic, and nutritional parameters and their influence on pregnancy outcome. Introduction to part III. PMID- 8494259 TI - Iodine supplementation and the prevention of cretinism. AB - Normal development of the CNS requires adequate thyroid hormone exposure. Since iodine is an essential component of the thyroid hormone molecule, its deficiency during fetal development can cause hypothyroidism and irreversible mental retardation. The full-blown syndrome, called cretinism, includes deaf-mutism, short stature, spasticity, and profound mental retardation. The clinical spectrum can vary in degree and combination of these features. Screening programs in iodine-deficient countries show that up to 10% of neonates have elevated serum TSH levels, putting them at theoretical risk for permanent brain damage. About one billion people worldwide risk the consequences of iodine deficiency, all of which can be prevented by adequate maternal and infant iodine nutrition. Iodized salt is usually the preferred prophylactic vehicle, but iodized vegetable oil, iodized water, and iodine tablets are also occasionally used. The United Nations and the heads of state of most countries have pledged the virtual elimination of iodine deficiency by the year 2000. This goal is technically feasible if pursued with sufficient vigor and resources. PMID- 8494260 TI - Selenium teratogenesis. Species-dependent response and influence on reproduction. PMID- 8494261 TI - Zinc status in pregnancy: the effect of zinc therapy on perinatal mortality, prematurity, and placental ablation. AB - Zinc is present in and indispensable to all forms of life. Zinc is essential for the normal growth of human beings, and zinc proteins have been shown to be involved in the transcription and translation of the genetic material. Zinc deficiency has been incriminated in infertility, abortions, malformations, fetal intrauterine growth retardation, premature and postmature births, perinatal death, and abnormal deliveries with dystocia and placental ablation. Risk groups for developing zinc deficiency, which in turn might modify the expression of the underlying disease, are found among those with insufficient food intake, especially in protein malnutrition; abnormal mucosal uptake, as in celiac disease; abnormal intestinal losses, as in steatorrhea and inflammatory bowel disease; abnormal renal excretion, as in diabetes with insufficient metabolic control; alcoholism; and treatment with diuretic drugs. Zinc deficiency could be identified by means of fasting serum or plasma samples or the more laborious estimation of zinc in leucocytes or monocytes if sampling and handling is carefully performed and if stressful situations and acute-phase reactions as fever, delivery, or abortion are avoided. Zinc therapy in identified low-zinc groups has given favorable results and has reduced the frequencies of premature birth, placental ablation, perinatal death, and postmaturity. It is suggested, as we did in 1980, that these data are compatible with the presence of a zinc deficiency syndrome in pregnancy, which includes increased maternal morbidity, abnormal taste sensations, abnormally short or prolonged gestations, inefficient labor, atonic bleeding, and increased risks to the fetus such as malformations, growth retardation, prematurity, postmaturity, and perinatal death. PMID- 8494262 TI - Nutritional factors underlying the expression of the fetal alcohol syndrome. PMID- 8494263 TI - Maternal nutritional factors and congenital anomalies: a guide for epidemiological investigation. Introduction to Part IV. PMID- 8494264 TI - Prenatal protein malnutrition and postnatal brain function. PMID- 8494265 TI - Retinoids in embryonic development. PMID- 8494266 TI - Abnormal metabolism and the risk for birth defects with emphasis on diabetes. PMID- 8494267 TI - Vitamin and mineral status of women of childbearing potential. AB - Increasing data suggest a role for micronutrients in pregnancy outcome, and in some cases nutritional status must be adequate in the first weeks of pregnancy. We examined nationally representative survey data on women of childbearing age: the NHANES II data for serum measures of iron status and the CSFII four-day data for dietary measures of intake of protein, iron, zinc, folic acid, and vitamins A, C, and B6. For those nutrients, women below or near poverty had consistently lower levels, with median intakes below the RDA for all but protein (e.g., folic acid, 150 micrograms in contrast with the RDA of 180 for nonpregnant and 400 for pregnant women; for B6, 0.96 mg instead of 1.6 or 2.2). Even among women with incomes as high as three times the poverty level or more, large segments of the population had very low intakes. For example, the 25th percentile in that group was only 142 micrograms/day of folic acid, 4.6 alpha-tocopherol equivalents of vitamin E, 6.7 mg zinc, and 433 mg of calcium. Approximately 15% of women had low transferrin saturation. PMID- 8494268 TI - Lifestyle and environmental factors that can adversely affect maternal nutritional status and pregnancy outcomes. PMID- 8494269 TI - Case-control study of vitamin supplementation and neural tube defects. Consideration of potential confounding by lifestyle factors. PMID- 8494270 TI - Influence of maternal nutrition on pregnancy outcome: public policy issues. Introduction to Part V. PMID- 8494271 TI - Preconceptional nutrition and reproductive outcomes. PMID- 8494272 TI - Medical advice on maternal weight gain and actual weight gain. Results from the 1988 National Maternal and Infant Health Survey. AB - Weight gain advice showed a notable shift for white married mothers during the 1980s, with a large decline in reported advice of less than 22 pounds concomitant with a substantial increase in reported advice of 28 pounds or more. For black married mothers, there was little change in reported advice, except in the proportion of mothers who said they were advised to gain at least 35 pounds, which increased from 2 to 11%. It should be noted that it is not possible to corroborate the information on weight gain advice reported by mothers in 1980 or 1988 because of the lack of similar information from the providers of prenatal care. However, for the 1996 NMIHS, the feasibility of collecting such information from prenatal care providers will be examined. In view of the strong, positive relationship between maternal weight gain and birth weight, optimum weight gain advice for white and black mothers is critical. A recent nationwide survey of practicing dieticians found that 26% of the pregnant mothers they counseled believed that one shouldn't gain more than 20 pounds during pregnancy and that obese women didn't need to gain any weight at all. These beliefs were often culturally transmitted. Although only 12% of white mothers reported advice that did not meet the minimum standard in effect in 1988 and 19% reported advice that did not meet the minimum 1990 IOM guideline for their weight and height, a significantly higher proportion of black mothers reported advice of less than 22 pounds (33%) or the IOM minimum (34%). The far more frequent inappropriate advice reported by black than white mothers cannot be explained by differences in body mass index, age, education, parity, marital status, or site of care. Nevertheless, compliance with advice was almost the same for black and white mothers: More than 70% gained at least 22 pounds when this was the reported weight gain advice. It is thus entirely feasible that more appropriate advice for black women will result in significantly higher weight gains and improvement in infant birth weight and health. PMID- 8494273 TI - Preventing low birth weight: does WIC work? A review of evaluations of the special supplemental food program for women, infants, and children. PMID- 8494274 TI - How women perceive teratogenic risk and what they do about it. PMID- 8494275 TI - Maternal thiamine deficiency. A factor in intrauterine growth retardation. PMID- 8494276 TI - Adolescent pregnancy. Zinc supplementation and iron effects. PMID- 8494277 TI - Adolescent pregnancy. Weight and zinc supplementation effects. PMID- 8494278 TI - Conceptional biotransformation of microinjected retinoids. Correlations with dysmorphogenic activities. PMID- 8494279 TI - A new threshold model for cleft lip in mice. PMID- 8494280 TI - Vitamin A status of low-income pregnant women in Iowa as assessed by the modified relative dose-response. PMID- 8494281 TI - Studies of possible preventive effects of prenatal retinoic acid treatment on genetic birth defects in mice. PMID- 8494282 TI - The effect of nutrient intake on pregnancy outcome in maternal phenylketonuria. PMID- 8494283 TI - Is low serum magnesium associated with premature labor? PMID- 8494284 TI - Nutrition recommendations and practices of obstetrician-gynecologists before conception and during pregnancy. A national survey. PMID- 8494285 TI - Serum concentrations of trace elements in infants and their mothers during pregnancy. PMID- 8494286 TI - Manganese status during pregnancy. PMID- 8494287 TI - Tobacco smoking by pregnant women. Disturbances in metabolism of branched chain amino acids and fetal growth. AB - Pregnancy alone lowered the plasma AA concentrations of ileu, leu, and val when compared to their concentrations in nonpregnant nonsmokers. Plasma concentrations of val, ileu, and leu were significantly higher in pregnant smokers than in pregnant nonsmokers. Therefore, the utilization of BCAA was more reduced in pregnant smokers than that which could be predicted from plasma AA concentrations of nonpregnant nonsmokers. PMID- 8494288 TI - Biological determinants of pregnancy weight gain in a Filipino population. PMID- 8494289 TI - Gestational protein deficiency enhances fetotoxicity of carbon monoxide. PMID- 8494290 TI - Premature rupture of amniotic membranes as functional assessment of vitamin C status during pregnancy. PMID- 8494291 TI - Primary and secondary zinc deficiency as factors underlying abnormal CNS development. PMID- 8494292 TI - Effects of altered maternal metabolism during gastrulation and neurulation stages of embryogenesis. AB - In summary, many congenital malformations are produced during gastrulation and neurulation stages of embryogenesis at a time when no definitive chorioallantoic placenta has been established. In rodents, altered maternal metabolism may have a direct impact on the embryo or an indirect impact via disruption of the nutritive function of the visceral yolk sac. If similar mechanisms operate in human embryos, these factors probably alter functions of the trophoblastic shell. In any case, it is crucial to remember that the metabolic status of the embryo is rapidly changing and during early stages of organogenesis may respond to alterations in nutrients quite differently during the first four weeks of gestation than at later stages of organogenesis and the fetal period. PMID- 8494293 TI - Morphological, biochemical, and functional consequences of vitamin B6 deficits during central nervous system development. PMID- 8494294 TI - Postulated mechanisms underlying the development of neural tube defects. Insights from in vitro and in vivo studies. AB - In recent years, use of animal models has resulted in acquisition of a significant amount of new information regarding normal and abnormal neural tube development. Studies of mutant and of teratogen-exposed mice are complementary, with each providing insights that promise to advance our understanding of the other. Analysis of teratogen-exposed embryos is best suited for identifying susceptible developmental stages and vulnerable populations. Advances in molecular genetics, with the ability to identify gene products, their cell/tissue location, and, potentially, to understand their function, will make naturally occurring as well as man-made mutants invaluable for understanding the heterogeneous mechanisms that underly NTDs. PMID- 8494295 TI - Possible abnormalities of folate and vitamin B12 metabolism associated with neural tube defects. PMID- 8494296 TI - The role of the human placenta in embryonic nutrition. Impact of environmental and social factors. AB - The human placenta has been implicated in the poor growth and development of the embryo/fetus due to alterations in blood flow and reductions in the transfer of nutrients such as amino acids and carbohydrates. Deficiencies of such nutrients have been the principal of many research investigations. The role of micronutrients, however, may also be major factors in appropriate growth and development, and there may be a general reduction in the availability of such nutrients, for example, the role of folate supplementation during early pregnancy and the reduction in the incidence of neural tube defects. Vitamins are not all transported via a common mechanism. Therefore, the modulation of human placental transport can be different for different vitamins, for example, A and B12. It is apparent that the human placenta can oxidatively metabolize retinoids (isotretinoin and tretinoin) to more toxic or less toxic metabolites. These metabolites can then be transferred to the fetal circulation. Such metabolism/transfer is in contrast to how vitamin B12 is bound to transcobalamin proteins, which are produced by the placenta and directionally released into the maternal and fetal circulations. PMID- 8494297 TI - Nonspecific immunomodulation influences the course and location of Cryptosporidium parvum infection in neonatal BALB/c mice. AB - The influence of nonspecific immunomodulation with Thymomodulin (a calf thymic extract with immunomodulatory activity) and hydrocortisone on the course and location of Cryptosporidium parvum infection in neonatal BALB/c mice (infected with 10(6) or 10(5) oocysts on day 7 of life) was studied using scanning electron microscopy of the inner surface of different parts of intestine. Daily peroral treatment of suckling mice with 20 mg/kg/day of Thymomodulin for 5 days before inoculation resulted in an earlier peak and earlier termination of cryptosporidial infection when compared with control infected mice. On the other hand, peroral administration of 25 mg/kg of hydrocortisone every second day led to the persistence of cryptosporidial infection in the ileum of immunosuppressed mice until the end of observation (day 15 post infection), whereas only transient infection was observed in the intestine of control infected mice. The location of infection was also altered in hydrocortisone--treated mice--the severe infection was observed in more proximal parts of the intestine (anterior and middle jejunum), whereas no cryptosporidia were found in these parts of the intestine in nontreated infected mice. PMID- 8494298 TI - [In vitro study of leishmanicidal agents with drug carriers]. AB - Antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioavailability of many potential antileishmanial compounds. In this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymer nanoparticles was explored. In the same way, polyisoalkylcyanoacrylate nanospheres which have, in vitro, trypanolytic properties were also tested. The study was performed in an in vitro model using Leishmania major amastigote stages within the U 937 human monohistiocytic cell line. The antileishmanial activities of unloaded or pentamidine-loaded nanoparticles were compared to those of the free drugs. The 50% effective concentration of targeted pentamidine was 0.10 microgram/ml, while it was up to 2.7 micrograms/ml with the free drug after a 24-hour incubation time. The pentamidine-bound nanoparticles proved to be 25 times more active than the free drug. Unloaded polyisoalkylcyanoacrylate nanoparticles destroyed intracellular amastigote stages (50% EC = 15 micrograms/ml) but at a level close to the cytotoxic concentration. PMID- 8494299 TI - Survival of first-stage Neostrongylus linearis larvae in ovine faeces under environmental conditions in Galicia (north-west Spain). AB - A study was made on the survival of first larval stage of Neostrongylus linearis, from November 1990 to October 1991, under natural conditions in an inland locality in Galicia (North-West Spain). The faeces were obtained from a sheep naturally infected with this nematode. Once a month, faeces were placed on a 0.5 x 0.5 m plot, in natural conditions, until we had 12 deposits. Samplings were done weekly until there was no more faecal matter in the plots. Larval survival was determined using the Baermann migration technique, and we calculated the number of larvae per gram after the transformation of the weight of the faecal sample, in order to discard weight variations owing to climatic conditions. Over the whole period of this study, the percentages of larval survival in the faeces of the 12 deposits changed from the first week onwards. In those samples that were left in the pasture more than three weeks, survival was less than 50%. After the seventh week only very small numbers of active N. linearis larvae were obtained. We observed a positive influence of relative humidity on survival during the first week's presence of the faeces in the pasture. In the same way, a statistically significant negative correlation was proved between larval survival in faeces and temperatures during the first three weeks post-deposit. PMID- 8494300 TI - Color flow ultrasound for delineating microsurgical vessels: a clinical and experimental study. AB - There is a need in plastic and reconstructive surgery for a method of monitoring flaps and replants pre- and postoperatively. This study evaluates color flow Doppler done as a monitoring technique for microvascular vessels. The capability of color flow ultrasound to monitor venous and arterial insufficiency and occlusion was studied by means of an experimental system in the Yucatan miniature swine model. A circulatory circuit in line with a magnetic flow probe is created. Measurements are made on the isolated hind limb of the animal. Color flow ultrasound is demonstrated to be a technique that is sensitive to venous and arterial insufficiency at flow rates as low as 3.0 ml/min. Characteristic waveform patterns are shown to predict arterial and venous insufficiency before they actually progress to occlusion. A clinical series of 25 postoperative patients is presented, consisting of volunteer studies as well as pre- and postoperative examinations of free flaps and replantations. Color flow ultrasound is shown to visualize a spectrum of pre- and postoperative microvascular conduits encountered in plastic and reconstructive surgery. PMID- 8494301 TI - Quantitative three-dimensional assessment of face-lift with an optical facial surface scanner. AB - Three-dimensional computed tomographic scan images of facial deformities provide information that has been useful in planning and evaluating therapy. However, the benefits of computed tomographic imaging in cosmetic plastic surgery are often insufficient to justify exposing the patient to radiation. This report describes application of an optical, noncontact, three-dimensional surface digitizer with subsecond scanning time for 360-degree examination of the human head. The resultant three-dimensional surface data are suitable for computer graphics display and manipulation, and for noncontact skin surface measurement. The scanner provides accurate and complete coverage of complex facial surfaces. This system was applied to digitization of the human head in the planning and evaluation of facial plastic surgery. The results indicate that the resulting image is accurate enough to detect subtle dimensional changes resulting from surgery, including postoperative edema and surface changes due to face-lift. This type of scanning can assist in a number of tasks performed by plastic surgeons, including collecting anthropomorphic measurements, preoperative and postoperative assessment, volume monitoring, customizing of implants, and interactive planning. PMID- 8494302 TI - Impact tolerances of the rigidly fixated maxillofacial skeleton. AB - A study was designed to determine how soon an athlete who undergoes rigid fixation of a facial fracture can return to full competition. The impact resistance of a rigidly fixated malar complex fracture was studied and compared with that of an intact malar complex. Twelve fresh human cadaver heads were used. A custom-designed impact device was used to deliver a blow of a specific energy to each intact malar complex. The subsequent fractures were rigidly fixated at three points using titanium miniplates and screws. A second impact of identical energy was delivered. The forces generated and the subsequent displacement of hard and soft tissues were recorded after each impact. It was concluded from this study that an impact to a rigidly fixated malar complex fracture produced less force and greater displacement of hard and soft tissues than an impact of identical energy to an intact malar complex. The potential for sustaining more severe maxillofacial injuries after an initial facial fracture should be seriously considered. The results suggest that sufficient time should be allowed for the bony healing of a facial fracture to occur, even after rigid fixation, before an athlete can resume full contact activities. PMID- 8494303 TI - Breast island flaps. AB - Breast reconstruction has been performed using neighboring skin flaps and more recently by using myocutaneous flaps. Nowadays, more conservative techniques have been proposed. Quadrantectomy combined with chemotherapy and radiotherapy offers similar survival time after treatment when compared with a more radical procedure. Techniques used by plastic surgeons for partial or total breast reconstruction have become inadequate for patients with mild breast resections. In effect, surgeons have been qualified for extensive resections, but not for small reconstructions. Lesions left after quadrantectomy become, in many situations, a difficult problem to solve aesthetically, due to the positioning of the defect in different quadrants. I describe here a new procedure that uses a breast tissue flap with its pedicle on the costal cage. Breast island flaps, also called "plug flaps," were created specifically after quadrantectomy or other types of partial breast resection, for an easier reconstruction. The anatomical basis of breast island flaps was studied in cadavers. The surgical technique and results are described and illustrated in clinical cases. PMID- 8494304 TI - Tripartite frontalis muscle flap transposition for blepharoptosis. AB - Transposition of frontalis muscle to the tarsus is an effective technique for correction of blepharoptosis with poor levator function. This is refined by division of the frontalis muscle flap into three strips, which are sutured separately to the upper tarsal border. Thirty-six patients with blepharoptosis (54 eyelids) had tripartite frontalis muscle flap procedures. The ptosis was congenital in 33 patients. Forty-eight eyelids had poor levator function. Six had fair levator function. The frontalis action ranged from 8 to 14 mm. The average of follow-up evaluation was 32 months. The postoperative results were evaluated by Berke's criteria, various sensation tests of the forehead, and presence of forehead wrinkles. The tripartite frontalis muscle flap provided an even distribution of upward pull on the tarsus without tenting the lid margin. Ptosis on superior and primary gaze, an intrinsic complication of maximal levator resection or frontalis suspension, was not observed after this procedure. Lagophthalmos was transitory, usually disappearing within 3 months. Lid lag was mild-to-moderate. Mild hypesthesia of the forehead returned completely to normal in all patients, followed more than 24 months. Slight lowering of the medial portion of the eyebrow and incomplete wrinkling of the forehead on upward gaze were mild cosmetic defects after correction in 4 patients with unilateral ptosis. The tripartite frontalis flap technique is recommended for patients with bilateral congenital ptosis and fair-to-poor levator function, and for unilateral ptosis, if either contralateral brow lift or bilateral frontalis transposition is appropriate. PMID- 8494305 TI - The benefit of a single-passage perfusion with a hypertonic citrate solution on the cold ischemia tolerance of epigastric free flaps in Dark-Agouty rats. AB - In this study the effectiveness of a single-passage perfusion with hypertonic citrate solution on the cold ischemia tolerance in epigastric free flaps in Dark Agouty rats was investigated. In the control group a significant decline in survival percentage was observed when the storage time was extended from 72 hours to 96 hours. A single (pressure controlled) passage perfusion with hypertonic citrate solution was able to prevent this decline. PMID- 8494306 TI - The ontogenetic transition of collagen deposition in rat skin. AB - Minimizing the morbidity of in utero surgery or, perhaps more important, capturing the unique characteristics of scarless remodeling, as is the fetal response to injury, demands better elucidation of the observed variations from adults in whom the normal progression of wound healing leads to fibrosis. Species dependent fetal phlogistic responses and wound scar formation represent a temporal continuum before the onset of adult patterns. We have analyzed skin collagen synthesis and content in Sprague-Dawley rats as one possible factor in this evolution showing that the fetal characteristics of a high percentage of type III collagen relative to type I and low total collagen content are maintained as long as the first 10 to 15 days postpartum. Although extrapolation of such a crucial "golden period" to justify the delay of human surgical procedures while still capturing the benefits of the fetal milieu remains speculative, anecdotal observations of minimal scar formation lend some credibility for performing less invasive maneuvers in the neonate. PMID- 8494307 TI - Congenital cutis laxa: a case report and review of loose skin syndromes. AB - Congenital cutis laxa is a deforming disease that may present for plastic surgical consultation during childhood. Failure to differentiate cutis laxa, with near normal wound healing, from the other forms of hyperelasticity syndromes with poor wound healing, has historically led to conflicting recommendations regarding the surgical management of patients presenting with loose skin. A face-lift and direct nasolabial fold excision was performed in a 10-year old patient with congenital cutis laxa with a good result. The other major syndromes presenting with loose skin as a clinical feature are reviewed and distinguished from cutis laxa. Plastic surgical procedures can be aesthetically and psychologically beneficial in children with congenital cutis laxa, and can be recommended without overt fear of wound disruption, poor scarring, and medical catastrophies that can occur with other hyperelasticity syndromes. PMID- 8494308 TI - Congenital absence of nasal bones. AB - Isolated congenital nasal malformation is rare; the isolated absence of any specific nasal structure is even rarer. They are related to craniofacial stenosis syndromes and to facial cleft, which are described in Tessier classification; also they can appear in 58 complex genetic syndromes. Nasal malformations may be acquired as a consequence of traumas, tumors, infectious diseases, or sequelae of aesthetic surgery. Gorham's syndrome is a rare disease that produces spontaneous and asymptomatic disappearance of any bone of the skeleton. In the world literature, there is no case of Gorham's syndrome with disappearance of the nasal bones. This case report is of a 20-year-old patient who sought correction of an aesthetic defect produced by a cartilaginous hump without the presence of the nasal bones. The absence of both nasal bones is produced by failure of the development of both centers of ossification. Through study of embryological development of the nasal structure, isolated absence of the nasal bones can be explained. PMID- 8494309 TI - Inhibition of perioperative platelet aggregation using toradol (ketorolac). AB - Traditionally, aspirin is used as an inexpensive and usually well-tolerated agent to accomplish inhibition of platelet aggregation after microvascular surgery. Occasionally, however, aspirin is contraindicated. We have successfully used Toradol (ketorolac) after microvascular tissue transfer to inhibit platelet aggregation postoperatively, and documented this in our laboratory. We present two individuals on our surgical service requiring microvascular free tissue transfer with documented allergic reactions to aspirin. Platelet function was successfully suppressed while on the Toradol regimen, and this function returned to normal within 24 hours after stopping this therapy. We believe this agent may have some use for the microvascular surgeon for the population of patients in which aspirin is contraindicated or difficult to administer. PMID- 8494310 TI - The subgalea-periosteal turnover flap for reconstruction of scalp defects. AB - Subgalea-periosteal flaps were successfully used in a turnover pattern to reconstruct two scalp defects with exposed calvaria caused by tumor ablation. A copious vascular network of the subgaleal fascia in the base and its attached lateral territories provide adequate blood inflow for the turnover flap. The periosteum is included in the flap to protect the blood supply of the subgaleal component from damage during dissection, and its uniform surface constitutes an ideal bed to receive skin grafts. The tissue is readily available and a large flap can be created in a single surgical step without deformities or sequelae left in the donor area. The subgalea-periosteal turnover flap overlaid with skin graft seems to make reconstruction of the complicated scalp defect much simpler and straightforward. PMID- 8494311 TI - Rhabdomyolysis and lower extremity compartment syndrome due to influenza B virus. AB - Rhabdomyolysis is an unusual complication following infection with influenza B virus. We recently managed a young boy who presented with severe rhabdomyolysis and bilateral lower extremity compartment syndrome due to infection with influenza B virus. PMID- 8494312 TI - Chronic pressure ulcer carcinomas. AB - Carcinomas arising from chronic pressure ulcers, Marjolin's ulcers, are an uncommon occurrence. They are virulent cancers that require aggressive surgical treatment. We present 3 such cancers including the first report of a squamous cell carcinoma arising in a distal extremity pressure ulcer. Carcinomas arising in chronic pressure ulcers behave more aggressively than other types of Marjolin's ulcers and, therefore, they need to be treated more aggressively. Extensive surgical excisions with wide surgical margins are necessary and elective lymph node dissections should be considered for optimal therapy. PMID- 8494313 TI - Review of the literature on construction of a neourethra in female-to-male transsexuals. AB - Voiding in a male fashion has priority for most female-to-male transsexuals. For that reason, lengthening of the urethra has been attempted by various surgeons. Because constructing a neourethra has frequently led to fistulas and strictures, some authorities abandoned their attempts. In this report, a review of the literature on the construction of a pars pendulans and a pars fixa urethrae in phalloplasty is given. The techniques used in our institute are mentioned. The use of local tissue for lengthening of the fixed part of the urethra can be successful in case a vaginal flap is incorporated. In phalloplasty, the free flap technique is a useful alternative to the use of pedicled flaps. The techniques necessitating opening the abdomen and viscera are too elaborate and too risky to be used as routine procedures. The use of external devices for urination as suggested by some investigators is not only unsatisfactory to the patient, it also carries the risk of urinary duct infection and trauma. PMID- 8494314 TI - Winds of change. PMID- 8494315 TI - [Carotid injuries. Apropos of 5 cases]. AB - The authors use a series of 5 treated carotid wounds to identify the characteristics of these lesions and their management. The gravity of carotid wounds is due to the risk of hemorrhage as well as that of respiratory distress and secondary neurological deficit. Controversy persists regarding the legitimacy of revascularisation procedures in the presence of neurological lesions and, according to the majority of authors, such an approach is recommended unless the patient is in coma. PMID- 8494316 TI - [Embryology of vessels]. AB - Endothelial emergence is the best known aspect of vessel formation during embryogenesis. It has been analyzed in an avian model of chimeras at the time of organogenesis or morphogenesis. These chimeras involve two species, chick and quail, whose cells may be distinguished on the basis of distinct nuclear heterochromatin patterns or through the use of antibodies that are species and lineage specific. QH1, a monoclonal antibody obtained in our group, whose affinity is restricted to the quail hemangioblastic lineage (endothelial and hemopoietic cells), has been a sensitive probe to study the origin of these cells in various chimeric patterns. By transplanting organ rudiments or primordial germ layers, we have shown that endothelium emergence in organ rudiments occurs through two different mechanisms, vasculogenesis or in situ differentiation, and angiogenesis or colonization by extrinsic precursors. Vasculogenesis occurs in the mesoderm of internal organ rudiments while angiogenesis occurs in external rudiments. The conclusion is that associated endoderm exerts a positive influence on the emergence of endothelial progenitors from mesodermal precursors. PMID- 8494317 TI - [Saccular aneurysms of the renal artery]. AB - The increasingly frequent use of arteriography in the investigation of hypertension and of obliterative arterial disease of the lower limbs has led to recognition of the actual incidence of renal artery aneurysms. The importance of this type of lesion is due to the fact that the natural history of renal artery aneurysms remains unknown, their relationship with hypertension is still controversial and the risk of complications, and rupture in particular, has led to the suggested possible need for their routine surgical excision. The current trend is to limit indications for surgery to certain specific cases since a number of recent series have shown that the risk of rupture of a small saccular aneurysm was very small. PMID- 8494318 TI - [Efficacy of intravenous milrinone in the treatment of acute congestive cardiac failure. Results of a French multicenter study]. AB - The hemodynamic effects and safety of milrinone, a phosphodiesterase inhibitor, were studied in 57 patients in the acute phase of cardiac failure. The drug was given intravenously as an initial push dose of 50 micrograms/kg in 10 min followed by a 24 hour infusion at the dose of 0.5 micrograms/kg/min. Maximal response was obtained after 15 min and persisted throughout the infusion. Cardiac index rose by 40%, while pulmonary capillary pressure fell from 25 mmHg to 17 mmHg (-30%) by the fifth minute of treatment. Mean pulmonary artery pressure fell by 20% by the 15th minute. Systemic resistance decreased by 26% and pulmonary vascular resistance by 22%. All these variations were significant. Heart rate and systemic blood pressure remained stable. Study of three sub-groups: digoxin vs non-digoxin, sinus rhythm vs atrial fibrillation, and coronary patients vs non coronary patients, revealed no significant difference. Safety of the drug was good, no extra-cardiac actions having required interruption of the infusion. Stoppage was made necessary by two instances of ventricular tachycardia. Improved hemodynamic effects and the good safety/acceptability of the drug indicate that milrinone is a treatment of choice in cardiac failure. PMID- 8494319 TI - [Efficacy and tolerability of sustained-release disopyramide in the treatment of cardiac arrhythmia. Results of a study with 593 patients]. AB - In the context of an open multicentre study, 593 patients participated in the evaluation of sustained release disopyramide (*) in the treatment of cardiac arrhythmias. One hundred and seventy one (29%) had a ventricular arrhythmia, 382 (64%) a supraventricular arrhythmia and 40 (7%) an atrial and ventricular arrhythmia. Two hundred and seventy patients (46%) had underlying cardiac disease. Disopyramide was administered at the mean daily dose of 462 +/- 95 mg. The effectiveness of treatment was assessed after 3 and 6 months by Holter in the group treated for ventricular arrhythmias, the responder rate was 52.6% at three months and 58.1% at 6 months. It was significantly (p < 0.001) greater in the group treated for supraventricular arrhythmias (71.3% at 3 months and 82.1% at 6 months). The Holter responder rate in patients aged over 65 (70.5% at 6 months) was high and general and cardiac acceptability similar to that in younger patients. Adverse events led to the interruption of treatment in 8.2% of patients. Thus the effectiveness/acceptability ratio of SR disopyramide makes it entirely appropriate for the treatment of cardiac arrhythmias, even in the elderly. PMID- 8494320 TI - [Dynamic cartography of flow patterns by cine-MRI. Presentation of the technique and preliminary results for major vessels]. AB - The authors report the principles, experimental evaluation and clinical approach of a method for dynamic imaging of flow patterns by NMRI, based upon the phase modulation technique. The imaging method is based upon gradient echo, functioning in "cine" and "flow compensated" mode. Modifications in this sequence enable attribution to the moving spins phase of a value which is considered to be proportional to the flow rate. A map of rates is then obtained from the phase image. Calibration of this sequence in vitro has shown excellent correlations between flow rate and the phase information thus obtained: r always > 0.98 for rates up to m/s. The first results obtained in vivo for the thoracic and abdominal aorta, in 11 control subjects, show that the technique is suitable for the study of pulsatile blood flow, providing very detailed information concerning the spatial distribution of flow rates. Mean flow in the suprarenal abdominal aorta (4.6 +/- 1.6 l/min) is 32% greater than that in the inferior vena cava (3.1 +/- 1 l/min), corresponding to an estimation of portal vein flow of 1.5 l/min. Practical limitations related to the use of a resistive magnet are nevertheless stressed and the authors list the technical aspects necessary for the better clinical utilisation of this non-invasive flowmetric technique. A review of the current literature forms the basis for an assessment of the potential importance of dynamic and quantitative NMRI of flow patterns in the cardiovascular area. PMID- 8494321 TI - [Acute myocardial infarction in patients over 70 years of age treated by immediate primary angioplasty]. AB - Twenty consecutive patients aged over 70, admitted for acute myocardial infarction, underwent coronary arteriography within less than 6 hours after the onset of pain to confirm the diagnosis and determine the indications for other than thrombolytic reperfusion treatment, the risk of thrombolysis seeming theoretically prohibitive. In all cases, the artery responsible was found to be obstructed and, based upon this criterion, primary reperfusion angioplasty was performed. The criterion for success of angioplasty was the reappearance of distal flow (grade > 1 of the TIMI classification--Thrombolysis in Myocardial Infarction). The reperfusion rate obtained by angioplasty was 85%. Follow-up coronary arteriography during hospitalisation (between D10 and D15) in 17 patients revealed neither restenosis nor re-occlusion. In case of successful reperfusion, left ventricular ejection fraction improved by 16% (in absolute values). Hospital mortality was 15% (6 patients were in cardiogenic shock from the time of admission). Mortality (after a follow-up of 27.3 +/- 17.5 months) was 20%. Complications of the procedure during the acute phase included one femoral hematoma and one moderate coronary dissection, with an uncomplicated outcome. Angioplasty is an effective reperfusion method in patients aged over 70, and is an alternative to thrombolysis which, in this age group, is accompanied by a risk of hemorrhagic complications, cerebral in particular. Thus angioplasty can be suggested as first line treatment in elderly patients provided they have been admitted to a unit where operational cardiology is available on a continuous basis. PMID- 8494322 TI - [Evaluation of a new cardiotonic agent on human isolated atrium]. AB - The action of a phosphodiesterase inhibitor, RGW 29 38, was analysed experimentally. A preliminary study with guinea pig isolated heart, using Langhendorf's method, revealed a cardiotonic effect, though less than with isoprenaline and dobutamine, with which it was compared. The inotropic action of the compound was then studied using human isolated atrium. The model is described. It consisted of measurement by a strain gauge of the contractions obtained in a stimulated atrial fragment obtained during a surgical procedure. The following parameters were analysed, expressed as percentage increase in relation to baseline conditions: maximum tension developed, positive dP/dt and negative dP/dt. The effect of RGW (n = 6) was compared with that of isoprenaline (n = 7). RGW caused an increase in maximum tension of 195% +/- 91%, in positive dp/dt of 110% +/- 72% and in negative dp/dt of 168 +/- 54%. This increase was, however, less than that seen in the isoprenaline group. Thus RGW had a definite positive inotropic effect on guinea pig isolated heart and human isolated atrium, though less than that of the catecholamines with which it was compared. Isolated human atrium appears to be a useful study model, in particular for analysis of the inotropic action of drugs. PMID- 8494323 TI - [Evaluation of electrophysiological properties of asymptomatic Wolff-Parkinson White syndromes. Comparison with symptomatic Wolff-Parkinson-White syndromes]. AB - The aim of this study was to compare the electrophysiologic properties of asymptomatic Wolff-Parkinson-White (WPW) syndromes with those of symptomatic WPW, and in particular the anterograde refractory period of the accessory tract and atrial vulnerability. This retrospective study involved 171 patients with WPW seen in their surface electrocardiogram, untreated, having undergone standard invasive electrophysiologic investigation. These patients were divided into two groups: group I consisting of 42 asymptomatic patients and group II consisting of 129 asymptomatic patients. 1) The mean anterograde refractory period (mean ARP) did not differ statistically between group I (330 +/- 97 msec) and group II (311 +/- 110 msec). The mean minimum interval between two preexcited complexes during atrial fibrillation (mean RR min) did not differ statistically between group I (313 +/- 80 msec) and II (300 +/- 105 msec). The mean retrograde refractory period (mean RRP) was significantly (p < 0.001) longer in group I (416 +/- 126 msec) than in group II (307 +/- 75 msec). 2) A reciprocal tachycardia was induced in 95% of cases in group II (122 patients) as compared with 9.5% of cases in group I (4 patients), with a very significant (p < 0.001) difference. Atrial fibrillation was induced in 24% of cases in group I (10 patients) and 34% of cases in group II (44 patients), the difference not being significant. 3) The incidence of potentially serious forms did not differ statistically between groups I and II. Nine patients in group I (21.4%) and 49 patients in group II (38%) had rapid anterograde conduction in the accessory tract (ARP or RR < or = 250 msec).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494324 TI - [Occlusive spasm of a coronary artery not treated during angioplasty. Apropos of a case]. AB - The authors report the case of a patient who, during percutaneous transluminal angioplasty of the circumflex artery, developed sudden occlusion of the anterior interventricular artery without stenosis and not touched by the operator. The fact that this occlusion was completely reversible after an intra-coronary injection of nitroglycerin suggests that this was due to spasm. This case suggests the possibility of consequences of angioplasty at a point distant from the dilated site. The authors use this case and a review of the literature to discuss the pathophysiological mechanisms which could be responsible for such consequences. PMID- 8494325 TI - [Double mitral orifice. Apropos of a case]. AB - The authors report a case of Double Mitral Orifice (DMO), existing in isolation and type 3 by the Floch Prigent classification. This rare anomaly is often associated with another congenital malformation, dominated by intra-atrio ventricular defect. Two-dimensional echocardiography is the essential diagnostic factor. Hemodynamic consequences may be nil, but mitral insufficiency and/or stenosis may complicate this malformation. Treatment may be summarised as abstention, surgical repair or valve replacement, according to the severity of lesions. PMID- 8494326 TI - [Severe pulmonary embolism and thrombus of the right atrium. Success of the thrombolytic treatment combining Rt PA and streptokinase]. AB - The authors report the case of a patient with a serious recurrence of pulmonary embolism with echocardiographic evidence of a floating serpentine thrombus of the right atrium. The outcome was rapidly satisfactory with disappearance of signs of acute cor pulmonale and lysis of the right atrial thrombus after infusion of two thrombolytic agents: Rt PA and streptokinase. There is no evidence in the literature to indicate that one form of treatment, i.e. surgical thrombectomy or thrombolysis, is markedly superior to the other. Thrombolysis appears to be a useful alternative to surgery. The use of Rt PA and of the combination of two thrombolytics has not been published previously and merits confirmation. PMID- 8494327 TI - Low plasma apolipoprotein AII levels in human and mouse amyloidosis with mutant transthyretin (Met-30) gene. AB - We measured the serum apolipoprotein levels in patients with familial amyloidotic polyneuropathy (FAP). The serum apolipoprotein AII levels were much lower than those of the control subjects, while the levels in asymptomatic carriers of the FAP gene were normal. Other plasma apolipoprotein levels, such as apolipoproteins AI, B, CII, CIII, and E, were all within normal ranges. The decrease of apolipoprotein AII in the plasma of FAP patients correlated with the progression of the disease. In a transgenic mice model of FAP carrying human variant transthyretin gene (Met-30), serum apolipoprotein AII levels were decreased in 1.5-year-old mice compared with control mice, while the 3-month-old mice had normal levels. These results suggest that apolipoprotein AII may play an important role in lipid metabolism or amyloid formation in patients with FAP. PMID- 8494328 TI - 3-Methylglutaconic aciduria in "optic atrophy plus". AB - Behr's syndrome consists of recessively inherited infantile optic atrophy, together with chronic neurological disturbances such as ataxia, extrapyramidal dysfunction, and juvenile spastic paresis. This syndrome was found to be relatively common among Iraqi Jews. For our study, 18 such patients underwent metabolic study. All 18 showed abnormally elevated excretion of 3 methylglutaconic acid in their urine. The basic enzymatic defect is as yet unknown. We recommend that patients with early optic atrophy, and especially those with motor dysfunction, be examined for this organic aciduria. PMID- 8494329 TI - Babinski and the diagnosis of amyotrophic lateral sclerosis. PMID- 8494330 TI - Cyclosporine-induced chorea after liver transplantation for Wilson's disease. PMID- 8494331 TI - Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen. AB - Lambert-Eaton myasthenic syndrome is a paraneoplastic neuromuscular disorder in which an immune response directed against a small-cell lung tumor crossreacts with antigens in the neuromuscular junction. To isolate and characterize the antigens, we screened a human fetal brain expression library with a high-titer serum from a patient with Lambert-Eaton myasthenic syndrome. This screening resulted in the isolation of a complementary DNA clone encoding an antigen we call myasthenic syndrome antigen B (MysB). Approximately 43% (3 of 7) of Lambert Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did. The predicted amino acid sequence of this clone shows a high degree of homology to the beta subunit of calcium channel complexes. The MysB pre-messenger RNA is alternatively spliced to yield 3 forms of the protein differing in the domain between two highly conserved alpha-helical segments. PMID- 8494332 TI - Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. AB - Thirty-one patients with large, focal cerebral demyelinating lesions are reported. Twenty-four patients had solitary lesions and 7 had multiple foci, the latter apparently of identical age. The lesions presented clinically and radiologically as brain tumors (gliomas or metastases) or as multiple cysts. Six patients were older than 57 years (2 in their 70s) at the onset of their symptoms. The demyelinating nature of the lesions was established through biopsy in each patient and all improved significantly after corticosteroid therapy. Three patients developed additional lesions during the follow-up periods ranging from 9 months to 12 years consistent with the course of multiple sclerosis. Twenty-eight patients did not develop additional lesions. These included 6 patients with multiple lesions at the onset. In 1 of the patients, the first symptoms developed 10 days after receiving vaccination against influenza. Two patients had concomitant malignancy (chronic monomyelogenous leukemia and retroperitoneal seminoma respectively) and 1 patient developed immunoblastic sarcoma in the opposite hemisphere after biopsy diagnosis and steroid treatment of her demyelinating lesion. Tumor-like masses of demyelination may occupy an intermediate position between multiple sclerosis and postinfectious/postvaccination encephalitis. The clinical course (history of vaccination in one instance, acute onset, good response to corticosteroids, no clinical or radiological evidence of new lesions in the great majority of patients) favored postinfectious/postvaccination encephalitis. Lesion size however greatly exceeded that of the small foci of perivenous demyelination seen in typical postinfectious/postvaccination encephalitis and tended to present as space-occupying masses. PMID- 8494333 TI - Alternating hemiplegia of childhood: studies of regional cerebral blood flow using 99mTc-hexamethylpropylene amine oxime single-photon emission computed tomography. AB - Alternating hemiplegia of childhood is a rare disorder of unknown cause associated with progressive neurological deterioration. We report the results of regional cerebral blood flow studies using 99mTc-hexamethylpropylene amine oxime single-photon emission computed tomography in 3 patients. These studies were performed during the hemiplegic attacks (n = 6) and during the symptom-free periods (n = 2). Six single-photon emission computed tomographic studies performed during hemiplegic attacks consistently showed relative hyperperfusion of the contralateral cerebral hemisphere. Two single-photon emission computed tomographic studies performed during the asymptomatic phase showed normal and symmetrical cerebral perfusion. This is the first definite demonstration of unilateral increase of cerebral blood flow in alternating hemiplegia. These findings support the possibility of a relationship between the cause of alternating hemiplegia and migraine. PMID- 8494334 TI - The audiospinal reaction in parkinsonian patients reflects functional changes in reticular nuclei. AB - Audiospinal facilitation using the soleus H-reflex as a test was compared in 16 control subjects and 23 parkinsonian patients. In the patients, facilitation was significantly reduced during the 75 to 150 msec after the conditioning stimulation. This reduction was seen bilaterally even in patients with a hemisyndrome. It was corrected by L-dopa but not by anticholinergic agents. Facilitation at the 75-msec delay showed an inverse linear correlation with the bradykinesia intensity (r = -0.7, p < 0.01). The results argue in favor of a reduced excitability of the nucleus reticularis pontis caudalis from which a reticulospinal tract emanates as effector of the audiospinal facilitation. This would represent another example of dysfunction of reticular nuclei in Parkinson's disease. PMID- 8494335 TI - Okadaic acid induces hyperphosphorylated forms of tau protein in human brain slices. AB - Hyperphosphorylated forms of the microtubule-associated protein tau are components of the paired helical filaments (PHFs) seen in patients with Alzheimer's disease. Slices of human lateral temporal cortex were obtained from tissues removed incidental to resections for intractable hippocampal epilepsy. Tau phosphorylation in temporal lobe slices was determined using mobility shifts after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunodetection with the monoclonal antibodies Alz-50, 5E2, and Tau-1. The results indicate that tau phosphorylation was altered in a dose-dependent manner by the phosphatase inhibitor okadaic acid, but not by N-methyl-D-aspartate, quisqualate, or kainate. The slowest mobility forms of tau, termed "PHF-like tau," produced by okadaic acid treatment were dephosphorylated by purified protein phosphatase 2B (calcineurin). Formation of PHF-like tau peptides was blocked by KN-62, 1[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4 phenylpiperazi ne, an inhibitor of Ca2+/calmodulin-dependent protein kinase II. The protein kinase inhibitor staurosporine also prevented formation of PHF-like tau. These data suggest that phosphorylation of tau is regulated by Ca(2+) dependent protein kinases and okadaic acid-sensitive protein phosphatases, alterations of which may be implicated in the pathogenesis of Alzheimer's disease. PMID- 8494336 TI - Glycogen branching enzyme deficiency in adult polyglucosan body disease. AB - Branching enzyme activity was assayed in muscle, peripheral nerve, and leukocytes from 2 Ashkenazi-Jewish patients with adult polyglucosan body disease and 1 African-American and 3 Caucasian patients with the same clinical and pathological features. Branching enzyme activity was normal in the muscle specimens from both Jewish and non-Jewish patients. However, the activity was markedly decreased not only in the leukocytes from the 2 Jewish patients (confirming previous findings), but also in peripheral nerve specimens, whereas it was normal in nerve tissue and leukocytes from all non-Jewish patients. These data confirm a branching enzyme deficiency in a subgroup of patients with adult polyglucosan body disease, and show that the defect is tissue-specific, suggesting that adult polyglucosan body disease has more than one biochemical basis. PMID- 8494337 TI - The quest for a cure. PMID- 8494338 TI - New antidepressants. PMID- 8494339 TI - Recent studies on the structure and function of multisubstrate flavin-containing monooxygenases. PMID- 8494340 TI - Covalent modifications of G-proteins. PMID- 8494341 TI - Adventures in autopharmacology: a biographic view with digressions into other matters. PMID- 8494342 TI - Molecular diversity of the dopamine receptors. PMID- 8494343 TI - Neuropeptide Y-related peptides and their receptors--are the receptors potential therapeutic drug targets? PMID- 8494344 TI - Effects of opioids on the hypothalamo-pituitary-adrenal axis. PMID- 8494345 TI - Respiratory tract uptake of inhalants and metabolism of xenobiotics. AB - The combined impact of new research regarding the dosimetry of inhalants, discussed in early paragraphs of this review, and the rapidly developing knowledge regarding the location and substrate specificities of the enzymes responsible for xenobiotic metabolism should soon lead to new insights into the causes and prevention of cancer and other diseases of the respiratory tract and may provide insight into the design of drugs used in the treatment of respiratory tract disease. Among the developments to be expected within the next decade are the following: 1. The issue of extrapulmonary versus intrapulmonary activation of lung prodrugs and protoxicants will be resolved by validation of the different dosimetries predicted for highly lipophilic inhalants compared to less lipophilic ones. 2. The possibly complex roles of P450 isozymes 1A1 and 2D6 and other forms in the causation of human lung cancer will undoubtedly be better understood in the next few years. 3. Interspecies comparisons of respiratory tract enzyme activities--both activating and detoxicating--will lead to improved use of laboratory animals as models for expected toxicological and pharmacological effects in humans. 4. The potential role of nasal uptake and metabolism in causing brain disease will be established or denied experimentally. 5. The complex relationships between host factors--such as hormone levels and the presence of inflammation--and metabolism-mediated toxicity will become clearer. 6. As new research results continue to illuminate the complexities of the interactions of xenobiotics with respiratory tract tissue, clues as to how best to administer drugs via the respiratory tract and understanding of changes in disease patterns--such as the recent shift in sites for lung cancer--will follow. PMID- 8494346 TI - Childhood lead poisoning and its treatment. PMID- 8494347 TI - Renal toxicity of the nonsteroidal anti-inflammatory drugs. AB - NSAIDs pose little threat of renal insult in normal, healthy persons at therapeutic dosages. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. Such acute noxious renal effects are mediated by products of arachidonic acid metabolism. Precipitous decrements in glomerular filtration and renal ischemia, manifested by increased serum creatinine and urea nitrogen, are possible. However, these effects are usually fully reversible with prompt discontinuation of the offending NSAID. Risk factors for the development of these acute renal effects are known. Acute interstitial nephritis with or without nephrotic syndrome is a rare form of renal toxicity that typically occurs between 2-18 months of use. Renal impairment may be so severe as to require temporary hemodialysis; however, renal function usually returns to normal upon discontinuation of the NSAID. The mechanism of acute interstitial nephritis is presumed to be of allergic origin but could also be caused by a reactive metabolite. Fenoprofen use appears to be associated with a much higher risk for its development. In contrast to the acute effects of NSAIDs, irreversible, analgesic-associated nephropathy manifested by papillary necrosis and chronic interstitial nephritis may occur following months to years of high doses of analgesic mixtures. The mechanism by which combination analgesics produce this form of renal injury is unknown and could be either a result of medullary ischemia or a direct effect of a reactive metabolite. An important issue to be resolved is the relationship between the acute, reversible, prostaglandin mediated renal effects of the NSAIDs and chronic, irreversible destruction, if such a relationship exists. Theoretically, continual or repeated decrements in renal function in patients with predisposing risk factors could cause or contribute to progressive deterioration in renal function. Elevations in blood pressure or interference with the effects of antihypertensive medications could theoretically also contribute to long-term renal deterioration. In addition to renal syndromes caused by NSAIDs that result in renal impairment, other transient effects on electrolyte and water metabolism may also occur. Reduced secretion of sodium may result in formation of edema, exacerbation of heart failure, or increased blood pressure. Hyporeninemic-hypoaldosteronism may produce hyperkalemia. Finally, reduced excretion of water has rarely caused hyponatremia. It has been suggested that NSAIDs may be renoprotective in patients with nephrotic syndrome. Others have suggested that sulindac is "renal-sparing" because of a unique metabolic pathway that supposedly limits the exposure of the kidney to the active sulfide metabolite.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8494348 TI - The pharmacology of Parkinson's disease therapy: an update. PMID- 8494349 TI - Cardiovascular toxicity of anabolic steroids. PMID- 8494350 TI - Prodrugs of peptides and proteins for improved formulation and delivery. PMID- 8494351 TI - Molecular and ionic mimicry of toxic metals. PMID- 8494352 TI - Gene therapy, concepts, current trials and future directions. AB - Since the initial human clinical trials of retroviral-mediated gene transfer in the USA in 1989, numerous additional protocols are in process or have been proposed. In the first therapeutic protocol, to treat the genetic disease ADA deficiency, encouraging signs of clinical benefit have been observed in the first two patients. Gene-marking properties are being extensively used in many protocols, particularly in the area of autologous bone marrow transplantation for various cancers. The drug delivery potential of gene therapy is initially being evaluated through delivery of various lymphokines and cytokines in cancer therapy protocols. Testing has also begun for other genetic diseases, Familial Hypercholesterolemia and Hemophilia B. Vector systems and retroviral vectors are developing rapidly, and a clinical trial using a liposome-based delivery has started. The pace of technical development and clinical application has intensified. Although significant clinical therapies are expected from these initial studies, the full potential of gene therapy for wide applications still requires innovative research programs, directed towards true in vivo vectors. PMID- 8494353 TI - The pharmacology of ATP-sensitive potassium channels. PMID- 8494354 TI - Amphetamine: effects on catecholamine systems and behavior. PMID- 8494355 TI - Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. AB - Endothelial dysfunction is an important early-recurring phenomenon in virtually all forms of ischemia-reperfusion, including a variety of circulatory shock states. The dysfunction appears to be triggered within 2.5 min of the endothelial generation of a large burst of superoxide radicals. However, the initial dysfunction may be amplified by neutrophil-generated factors including oxygen derived free radicals, cytokines, proteases, and lipid mediators. Moreover, adhesive molecules on the surface of the PMN, along with their ligands on the endothelial cell membrane, appear to promote endothelial dysfunction in ways that may go beyond the adherence of neutrophils on the endothelial surface. These interactions remain to be elucidated but may involve intricate cell signaling pathways. A variety of pharmacologic agents exert endothelial protective effects in ischemia-reperfusion and circulatory shock states. Table 1 summarizes these agents and indicates the major mechanism of preservation of the endothelium. These substances can be classified into three broad categories: (a) substances replacing endogenous cytoprotective agents of endothelial origin including prostacyclin (PGI2), endothelium-derived relaxing factor (EDRF), and adenosine: the endothelium protecting agents include these substances as well as stable analogs of PGI2, and nitric oxide donors; (b) substances that inhibit pro inflammatory mediators of endothelial origin: the pro-inflammatory agents are primarily platelet activating factor (PAF) and oxygen-derived free radicals (e.g. superoxide radicals) although other mediators may be involved. The therapeutic agents useful in this area are PAF receptor antagonists and free radical scavengers (e.g. superoxide dismutase); (c) substances that inhibit neutrophils or neutrophil-derived mediators: the major neutrophil-derived mediators are oxygen-derived free radicals, cytokines (e.g. TNF alpha and IL-1 beta), proteases (e.g. elastase), and lipid mediators (e.g. LTB4). In addition, adhesive molecules on the neutrophil surface and their endothelial ligands promote endothelial dysfunction and the action of adherent neutrophils. Agents that inhibit some of these mediators are transforming growth factor-beta (TGF-beta), elastase inhibitors, leukotriene B4 (LTB4) receptor antagonists and monoclonal antibodies to adhesive proteins (e.g. anti-CD18, anti-ICAM-1). Further work is needed to clarify these findings and to determine the physiologic and pathophysiologic interactions among these diverse agents. This topic of endothelial dysfunction represents a fertile area for further investigation to elucidate the complex mechanisms of neutrophil-endothelial interactions. These interactions lead to neutrophil adherence to the endothelium, neutrophil migration into the underlying tissues, and subsequent tissue injury (e.g. myocardial reperfusion injury).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8494356 TI - Anti-inflammatory peptide agonists. PMID- 8494357 TI - Antimicrobial strategies in the care of organ transplant recipients. AB - Since the early days of transplantation, infection has been a major consequence of antirejection immunosuppressive therapy. Increasingly effective prophylactic and preemptive strategies are being developed to prevent the infectious consequences of immunosuppressive therapy. Although the data base is incomplete and there remains a compelling need for well-designed, randomized, comparative trials, the potential for controlling life-threatening viral, bacterial, fungal, and protozoal infections exists. The cornerstone of this effort is the recognition that effective immunosuppressive strategies require an antimicrobial program to make them safe and that such an antimicrobial program needs to be individualized in order to be appropriately matched with the needs of the antirejection program. Thus, escalation and de-escalation of the antimicrobial program should be carried out to match the immunosuppressive program. Infection and rejection remain closely intertwined, linked by the immunosuppressive program that is prescribed. PMID- 8494358 TI - Susceptibility of Staphylococcus aureus growing on fibronectin-coated surfaces to bactericidal antibiotics. AB - Several recent studies have shown that bacteria either grown in vitro as adherent biofilms or recovered from infected prosthetic devices have decreased susceptibilities to antimicrobial killing. To further study the microbial and environmental factors responsible for this decreased antibiotic susceptibility, we developed an in vitro model of surface-adherent Staphylococcus aureus growing on polymethylmethacrylate coverslips coated with pure fibronectin. After exponential growth for 4 h, the population of fibronectin-attached S. aureus remained constant for a further 48-h period, as evaluated by CFU counts of organisms quantitatively removed from the coverslips. At selected time points, surface-bound organisms were exposed to bactericidal concentrations of either oxacillin, vancomycin, fleroxacin, or gentamicin in short-term (0.5 to 2 h) or long-term (24 h) killing assays. Whereas at 2 h surface-growing organisms were still optimally killed by all antimicrobial agents, at 4 and 24 h attached bacteria expressed markedly altered susceptibilities to these agents. The decrease in susceptibility was moderate for fleroxacin, more important for oxacillin and vancomycin, and extensive for gentamicin. When surface-attached S. aureus was compared with bacteria grown in a fluid phase, both populations showed a parallel time-dependent decrease in their susceptibilities to either oxacillin, vancomycin, or fleroxacin. In contrast, attached organisms became considerably more resistance to gentamicin than suspended bacteria did. Subpopulations of organisms spontaneously released from coverslips during antibiotic exposure also showed markedly reduced susceptibilities to antimicrobial killing. This simple model of S. aureus colonization of in vitro fibronectin-coated surfaces might represent a useful approach to the study of the physiological and biochemical changes that underlie the decreased antibiotic susceptibilities of biomaterial attached organisms. PMID- 8494359 TI - Activities of fluoroquinolone, macrolide, and aminoglycoside drugs combined with inhibitors of glycosylation and fatty acid and peptide biosynthesis against Mycobacterium avium. AB - Smooth- and rough-colony variants of Mycobacterium avium serovar 4 were treated with three classes of drugs. The drugs were chosen for their potential inhibitory effects on the biosynthesis of the cell envelope-associated serovar-specific glycopeptidolipid antigens. Growth was monitored radiometrically with a BACTEC 460-TB instrument, and MICs were determined for each drug. Both variants were then treated with inhibitory drugs in combination with antimicrobial agents that have demonstrated effectiveness against M. avium. No growth inhibition was observed with 6-fluoro-6-deoxy-D-glucose or avidin. Inhibitors of glycosylation, i.e., 2-deoxy-D-glucose, bacitracin, and ethambutol, were inhibitory to smooth- and rough-colony variants, whereas drugs that inhibit peptide synthesis, i.e., N carbamyl-L-isoleucine and m-fluoro-phenylalanine, were more inhibitory for the rough-colony variant. Cerulenin, which affects fatty acid synthesis, was inhibitory for both variants, but it appeared to be more effective at inhibiting the growth of the smooth-colony variant at equivalent concentrations. Generally, when inhibitors of glycosylation were used with sparfloxacin and amikacin, a synergistic effect was observed for only the smooth variant. When drugs that affect peptide synthesis were used in combination with amikacin, a synergistic effect was observed for the rough variant, and when cerulenin was used in combination with sparfloxacin or amikacin, a synergistic effect was observed for both variants. Lipid analysis revealed that although the rough variant lacks the serovar-specific glycopeptidolipid antigens, it does possess a group of phenylalanine-isoleucine-containing lipopeptides that may explain its different susceptibility patterns to m-fluoro-phenylalanine and N-carbamyl-L-isoleucine. The significance of these results is discussed with reference to various components in the cell envelope and their importance in cell wall permeability. PMID- 8494360 TI - Ciprofloxacin resistance in clinical isolates of Salmonella typhimurium obtained from two patients. AB - Two patients (patients A and B) infected with Salmonella typhimurium failed ciprofloxacin therapy, and the posttherapy isolates had reduced susceptibilities to quinolones; 6 of 11 isolates from patient B were also cross-resistant to chemically unrelated agents. No transferable resistance, chloramphenicol acetylating enzymes, or beta-lactamases were detected. For 13 of 14 isolates, the concentrations of ciprofloxacin that inhibited DNA synthesis by 50% were similar to the MICs, suggesting a mutation in gyrA. Insertion of pNJR3-2 (gyrA) in the posttherapy isolate from patient A and 5 of 11 of the posttherapy isolates from patient B resulted in lower quinolone MICs, also suggesting that resistance was due to a mutation in gyrA. Three of the five isolates also had reduced levels of accumulation of quinolones. All six cross-resistant isolates from patient B had reduced levels of accumulation of quinolones, but only one isolate had increased susceptibility when pNJR3-2 was inserted. Despite the lack of OmpF seen in five isolates from patient B, there was no correlation with decreased levels of quinolone accumulation. All isolates had identical smooth lipopolysaccharide profiles. The mechanism of apparently reduced accumulation has yet to be determined. PMID- 8494361 TI - The Pseudomonas cepacia 249 chromosomal penicillinase is a member of the AmpC family of chromosomal beta-lactamases. AB - Pseudomonas cepacia 249 produces an inducible beta-lactamase with penicillinase activity. The nucleotide sequence of the penA gene, which encodes this beta lactamase, was determined and found to include regions with a significant homology to the ampC-encoded beta-lactamases of members of the family Enterobacteriaceae and Pseudomonas aeruginosa. The predicted amino acid sequence of the PenA beta-lactamase contained 17 amino acids immediately preceding the putative active-site serine which were highly conserved among the enzymes of the AmpC family. Although the penA-coding sequence had a total GC content of 60%, the predicted codon usage was more characteristic of Escherichia coli ampC-encoded beta-lactamase, with 53% of the codons having G or C in the third position, in contrast to the values for the P. aeruginosa ampC (88.5%) or Pseudomonas cepacia (88 to 92%) metabolic genes. The inducible expression of penA can be regulated by the E. coli gene product AmpD. A putative P. cepacia AmpR homolog was associated with the positive regulation of both Enterobacter cloacae ampC and P. cepacia penA expression, as confirmed by gel retardation studies. The E. cloacae AmpR did not regulate penA expression. Thus, by homology studies, codon usage, and genetic analysis, the P. cepacia penA beta-lactamase appears to have been acquired from members of the family Enterobacteriaceae and belongs to the class C group of beta lactamases. PMID- 8494362 TI - Effects of sub-MICs of erythromycin and other macrolide antibiotics on serum sensitivity of Pseudomonas aeruginosa. AB - We examined the effects of sub-MICs of erythromycin (EM) and other macrolide antibiotics on the serum sensitivity of Pseudomonas aeruginosa. P. aeruginosa S-6 grown for 36 and 48 h on agar with 10 micrograms of EM per ml (1/10th the MIC) showed significantly increased sensitivity to human serum bactericidal activity compared with those of bacteria grown on agar without EM (P < 0.05). No changes in serum sensitivity were observed in bacteria grown for less than 24 h. This increased sensitivity was apparent even at a concentration of 1.5 micrograms of EM per ml (1/67th the MIC) in bacteria grown for 48 h (P < 0.01). Among the other macrolide antibiotics tested, clarithromycin also enhanced sensitivity to serum, but there were no changes in the sensitivities of bacteria grown on agar with kitasamycin, josamycin, rokitamycin, or oleandomycin even at a concentration of 12 micrograms/ml (1/16th, 1/16th, 1/8th, and 1/33rd the MICs, respectively). P. aeruginosa S-6 grown on agar with subinhibitory concentrations of EM showed decreased cell surface hydrophobicity in a dose-dependent manner, whereas oleandomycin and rokitamycin, even at a concentration of 12 micrograms/ml, induced a slight decrease in hydrophobicity which was approximately equivalent to that of 1.5 micrograms of EM per ml. Among six other strains of the nonmucoid phenotype, three strains became more sensitive to serum by exposure to 10 micrograms of EM per ml for 48 h. In contrast, no evident correlation between EM treatment and a change in serum sensitivity was observed in six strains of the mucoid phenotype, as judged by the results of experiments with both 2 and 0.4% serum. These results show that EM at subinhibitory concentrations enhances the serum sensitivity of some P. aeruginosa strains. Since induced serum sensitivity was accompanied by a decrease in bacterial cell surface hydrophobicity, EM may render P. aeruginosa more serum sensitive by changing the cell surface structure(s) of this organism. PMID- 8494363 TI - Effects of temperature on anti-Candida activities of antifungal antibiotics. AB - The relative growth (percentage of growth relative to control growth) of 767 Candida isolates representing five species was measured in microcultures at 25 and 37 degrees C. In the presence of 10(-4) M flucytosine, the distribution of relative yeast growth data indicated that Candida albicans isolates were less susceptible at 25 degrees C than at 37 degrees C, while the opposite was found with 4 x 10(-5) M amorolfine for most of the isolates tested. Repetition of the experiments at four different temperatures with 99 C. albicans isolates and five antifungal agents confirmed a direct relationship between growth inhibition and increasing temperature from 25 to 40 degrees C with amphotericin B, flucytosine, and terconazole; a strong inverse relationship between inhibition and temperature with amorolfine; and a weak inverse relationship with terbinafine. However, these relationships were not always noted with other Candida spp.: in particular, the growth of C. glabrata and C. parapsilosis isolates tended to be greater at 37 degrees C than at 25 degrees C in the presence of the azole-derivative antifungal agents itraconazole and terconazole. These findings stress the species-specific individuality of yeast susceptibility to azole antifungal agents. The results with C. albicans and amorolfine and terbinafine accord with their known in vivo efficacy in mycoses involving low-temperature superficial sites and poor activity against mycoses involving deep body sites. The data also reinforce the need for control of experimental variables such as temperature in the design of standardized yeast susceptibility tests. PMID- 8494364 TI - Efficacy of prophylaxis with beta-lactams and beta-lactam-beta-lactamase inhibitor combinations against wound infection by methicillin-resistant and borderline-susceptible Staphylococcus aureus in a guinea pig model. AB - Although some beta-lactams and beta-lactam-beta-lactamase inhibitor combinations exhibit activity against methicillin-resistant Staphylococcus aureus, there remains the concern that therapeutic failures may result from the selection of resistant subpopulations. The prophylactic use of these antibiotics in clean surgery, however, may prove adequate since wound infections arise from the inoculation of small numbers of bacteria. In this clinical setting, heterogeneity in the phenotypic expression of beta-lactam resistance may facilitate antibiotic efficacy. Similarly, beta-lactamase-mediated resistance in S. aureus is dependent on inoculum size, and it may be possible to prevent infection from small inocula with relatively labile beta-lactams. To test this hypothesis, antibiotics were administered to guinea pigs as prophylaxis against infection by two methicillin resistant strains and one borderline-susceptible strain. Following prophylaxis with sulbactam or placebo, inoculation of only a dozen or fewer bacteria had a 50% probability of creating an abscess (50% infective dose [ID50]). The efficacy of ampicillin was similar to that of cefazolin, exhibiting moderate activity against the borderline-susceptible strain (ID50s, greater than 300 bacteria) and minimal activity against the methicillin-resistant strains (ID50s, fewer than 100 bacteria). Coadministration of sulbactam with ampicillin or cefazolin yielded better results than the beta-lactam alone for five of six strain-beta-lactam combinations, including an 80-fold increase in the efficacy of ampicillin sulbactam compared with that of ampicillin for one methicillin-resistant strain (ID50s, 2,017 and 25 bacteria, respectively). Prophylaxis with beta-lactams, especially beta-lactam-beta-lactamase inhibitor combinations, reduces the risk of wound infection by beta-lactam-resistant S. aureus. PMID- 8494365 TI - Nucleotide sequence analysis and DNA hybridization studies of the ant(4')-IIa gene from Pseudomonas aeruginosa. AB - The ant(4')-IIa gene was previously cloned from Pseudomonas aeruginosa on a 1.6 kb DNA fragment (G. A. Jacoby, M. J. Blaser, P. Santanam, H. Hachler, F. H. Kayser, R. S. Hare, and G. H. Miller, Antimicrob. Agents Chemother. 34:2381-2386, 1990). In the current study, the ant(4')-IIa gene was localized by gamma-delta mutagenesis. A region of approximately 600 nucleotides which contained the ant(4')-IIa gene was identified, and DNA sequence analysis revealed two overlapping open reading frames (ORFs) within this region. Northern (RNA) blot analysis demonstrated expression of both ORFs in P. aeruginosa; therefore, site directed mutagenesis was used to identify the ORF which encodes the ant(4')-IIa gene. No homology was found between ant(4')-IIa and ant(4')-Ia DNA sequences. Hybridization experiments confirmed that the ant(4')-Ia probe hybridized only to gram-positive presumptive ANT(4')-I strains and that the ant(4')-IIa probe hybridized only to gram-negative strains presumed to carry ANT(4')-II. Seven gram negative strains which had been classified as having ANT(4')-II resistance profiles did not hybridize with probes for either ant(4')-Ia or ant(4')-IIa, suggesting that at least one additional ant(4') gene may exist. The predicted amino-terminal sequences of the ANT(4')-Ia and ANT(4')-IIa proteins showed significant sequence similarity between residues 38 and 63 of the ANT(4')-Ia protein and residues 26 and 51 of the ANT(4')-IIa protein. PMID- 8494366 TI - Interaction of gentamicin with the A band and B band lipopolysaccharides of Pseudomonas aeruginosa and its possible lethal effect. AB - The lipopolysaccharide (LPS) of Pseudomonas aeruginosa PAO1 possesses two distinct types of O polysaccharide, A and B band LPSs, but the majority of clinical isolates from cystic fibrosis patients who are infected with the organism possess only the A band as the major LPS antigen. The initial step in a series of events during the uptake of aminoglycoside antibiotics such as gentamicin is the ionic binding of the molecule to the cell surface. In an attempt to elucidate the role of A and B band LPSs of P. aeruginosa in this passive ionic binding of gentamicin to the outer membrane and its possible lethal effects, strains PAO1 (A+B+) and LPS isogenic derivatives (A+B-,A-B+,A-B-) were treated with the antibiotic. Ionic binding of gentamicin appeared to be subtly different in PAO1 and its LPS derivatives; a lethal dose of drug was bound to all strains, although the degree of binding varied with each strain. The outer membrane affinity for gentamicin was higher in strains possessing the B band than in strains with A band LPS, and these B band strains were more prone to antibiotic-induced killing. Strains with both A and B band LPSs bound the most gentamicin of all strains, and this binding caused an almost 50% loss in viability. Ionic binding of aminoglycoside antibiotucs to the outer membrane of cell surfaces must not only weaken th cell surface (R. E. W. Hancock, Annu. Rev. Microbiol. 38:237-264, 1984; N. L. Martin and T. J. Beveridge, Antimicrob. Agents Chemother. 29:1079-1087, 1986; S. G. Walker and T. J. Beveridge, Can. J. Microbiol. 34:12-18, 1988) but it must also be more important in cell death than was originally thought. PMID- 8494367 TI - Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice. AB - The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 x 10(6) CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 10(6) CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80% when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 10(6) CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50% was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 10(5) and 1 x 10(5) intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 10(5) C. albicans. Mice infected with 10(5) C. albicans and treated with cilofungin (25 mg/kg) twice a day for 10 days had no organisms in the kidney, spleen, and liver at days 8, 2, and 8, respectively. There was 1-log-unit reduction in C. albicans counts in brain tissue from mice of one of the treated groups between 2 h and 2 days postinfection, after which the numbers of organisms remained the same until day 12. These data demonstrate the efficacy of cilofungin in the treatment of disseminated C. albicans infections in normal and granulocytopenic mice. The treatment regimen used in this study was able to clear C. albicans from the kidneys, spleen, and liver but not from brain tissue. PMID- 8494368 TI - Pharmacokinetics and bactericidal activities of one 800-milligram dose versus two 400-milligram doses of intravenously administered pefloxacin in healthy volunteers. AB - Pefloxacin pharmacokinetics and serum bactericidal activities (SBA) against Escherichia coli and Staphylococcus aureus were compared after intravenous infusion of either a single 800-mg dose or twice-daily 400-mg doses into 16 healthy volunteers. Plasma pefloxacin concentrations were measured for up to 60 h, and SBAs were determined 1, 12, and 24 h after the start of the infusion. The mean areas under the concentration-versus-time curve for plasma were not different (138 versus 136 h.mg/liter). The mean clearances, volumes of distribution, and half-lives were also comparable. The mean (+/- standard deviation) maximal concentration after the 800-mg infusion was 12.11 +/- 1.35 versus 6.51 +/- 0.73 mg/liter after the first 400-mg infusion and 7.42 +/- 0.76 mg/liter after the second 400-mg infusion. Mean trough concentrations at 24 h were significantly different: 2.77 +/- 0.63 (800 mg) versus 1.93 +/- 0.49 (400 mg twice) mg/liter (P = 0.0007). Mean SBAs against E. coli after 800 mg of pefloxacin were higher than 1/128 (1 h), 1/32 (12 h), and 1/16 (24 h). Mean SBAs against S. aureus under the same conditions were higher than 1/64 (1 h), 1/16 (12 h), and 1/8 (24 h). Mean SBAs at 1 and 12 h were significantly higher after the 800-mg infusion than after the 400-mg infusion but were similar at 24 h for both regimens. Comparison of SBAs according to National Committee for Clinical Laboratory Standards criteria showed a similar adequacy at 24 h for both regimens against both strains. Administration of 800 mg of pefloxacin once a day is bioequivalent to 400 mg twice a day, and bactericidal activity of the 800-mg infusion is not less than that of two 400-mg infusions. PMID- 8494369 TI - In vitro antimicrobial activity of a new antibiotic, MDL 62,879 (GE2270 A). AB - MDL 62,879 (GE2270 A) is a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu. MDL 62,879 was very active against gram-positive clinical isolates, particularly staphylococci and enterococci, for which MICs for 90% of isolates were < or = 0.13 micrograms/ml. It was equally active against isolates resistant to beta-lactams, erythromycin, gentamicin, and glycopeptides. It also had activity against Mycobacterium tuberculosis. MDL 62,879 had moderate bactericidal activity against staphylococci. PMID- 8494370 TI - In vitro activity of MDL 62,879 (GE2270 A) against aerobic gram-positive and anaerobic bacteria. AB - The in vitro activity of MDL 62,879, a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu, against a wide range of recent clinical isolates of common aerobic gram-positive and anaerobic organisms was determined. MDL 62,879 was highly active against staphylococci (MIC for 90% of isolates [MIC90], 0.125 microgram/ml), streptococci (MIC90, 1 microgram/ml), and enterococci (MIC90, 0.03 microgram/ml). All isolates of peptostreptococci and Mobiluncus spp. were susceptible, as were most isolates of clostridia. MDL 62,879 was not active against isolates of fusobacteria or Bacteroides spp., but some isolates of Prevotella spp. and Porphyromonas asaccharolytica were susceptible. PMID- 8494371 TI - Antimicrobial susceptibility of Acinetobacter species. AB - The in vitro activities of 16 antimicrobial agents against 180 Acinetobacter strains isolated from blood cultures (n = 162), central venous catheters (n = 11), and cerebrospinal fluids (n = 7) were studied. MICs were determined by a microtiter broth dilution method. Considerable differences in antimicrobial drug susceptibility against strains belonging to different species could be demonstrated. Acinetobacter baumannii isolates (n = 108) were generally more resistant than isolates identified as species other than A. baumannii. Multidrug resistance was common among A. baumannii isolates. Of the antimicrobial agents tested, imipenem was highly active against all A. baumannii isolates, and the other agents tested were only moderately active or inactive. Good activity against Acinetobacter species strain 3 was demonstrated for imipenem, amikacin, and ciprofloxacin. Most of the strains belonging to other species were susceptible to imipenem, ciprofloxacin, expanded-spectrum cephalosporins, amoxicillin-clavulanate, and the aminoglycosides but were resistant to ampicillin and older cephalosporins. PMID- 8494372 TI - The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants. AB - Nucleotide sequence analysis of ORF1 from the integron on the broad-host-range plasmid R751 revealed that the first 94 of 110 codons of ORF1 from R751 are identical to ORF4, an open reading frame from the 3' conserved segment of other integrons found in gram-negative bacteria, after which point they diverged completely. The predicted products of both ORF1 and ORF4 share homology with the multidrug exporter QacC. Phenotypic analysis revealed that ORF1 specifies a resistance profile to antiseptics and disinfectants almost identical to that of qacC, whereas ORF4 specifies much lower levels of resistance to these compounds. ORF4, whose product lacks the C-terminal 16 amino acids of the ORF1 protein, may have evolved by the interruption of ORF1 from the insertion of a DNA segment carrying a sulI sulfonamide resistance determinant. Hence, ORF1 was designated qacE, and its partially functional deletion derivative, ORF4, was designated qacE delta 1. Fluorimetric experiments indicated that the mechanism of resistance mediated by QacE, the protein specified by qacE, is active export energized by proton motive force. Amino acid sequence comparisons revealed that QacE is related to a family of small multidrug export proteins with four transmembrane segments. PMID- 8494373 TI - Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells. AB - The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth. PMID- 8494374 TI - Effect of oral antacids on disposition of intravenous enoxacin. AB - The effect of an intensive aluminum-magnesium hydroxide antacid regimen (Maalox TC) on the disposition of intravenous enoxacin was studied in six male and six female volunteers. A single 400-mg dose of enoxacin was administered intravenously over 30 min on two occasions separated by a 1-week washout period. Thirty milliliters of Maalox TC was administered at -8, -2.5, -0.5, 1.5, 3.5, 5.5, 7.5, 9.5, 11.5, 13.5, and 15.5 h relative to the start of one enoxacin infusion. The enoxacin dose in which antacid was coadministered was randomly selected. Fourteen plasma samples were collected over 24 h, and urine was collected in two divided intervals over 48 h. Enoxacin concentrations in plasma and urine samples were determined by high-performance liquid chromatographic assays. The intensive antacid regimen did not change the total clearance (P = 0.058) or steady-state volume of distribution (P = 0.516) for enoxacin. However, the nonrenal clearance and half-life were significantly altered (P < 0.05). The mean nonrenal clearance increased from 13.27 +/- 3.33 to 15.68 +/- 2.35 liters/h (18.2%) following the antacid regimen. This effect of antacid is unlikely to be of clinical significance. Enoxacin may be administered intravenously, but not orally, without regard to antacid treatment. PMID- 8494375 TI - Two mechanisms of butenafine action in Candida albicans. AB - The mechanism of action of a new benzylamine antimycotic, butenafine hydrochloride, was studied in Candida albicans by using the thiocarbamate antimycotic tolnaftate as a reference drug. Butenafine completely inhibited the growth of a test strain of C. albicans at 25 micrograms/ml and was cidal at 50 micrograms/ml. Tolnaftate did not show any growth-inhibitory activity up to 100 micrograms/ml. Both butenafine and tolnaftate inhibited squalene epoxidation in C. albicans, with 50% inhibitory concentrations being 0.57 and 0.17 microgram/ml, respectively. Butenafine, but not tolnaftate, induced the release of appreciable amounts of Pi from C. albicans cells at 12.5 micrograms/ml. This effect of butenafine was augmented when the cells were pretreated with tolnaftate. The results suggest that the direct membrane-damaging effect of butenafine may play a major role in its anticandidal activity and that the drug-induced alteration in the cellular sterol composition renders the cell membrane more susceptible to the membrane-damaging effect of this drug. PMID- 8494376 TI - Antimicrobial susceptibility of Pediococcus spp. and genetic basis of macrolide resistance in Pediococcus acidilactici HM3020. AB - We determined the MICs of 28 antimicrobial agents against 36 clinical strains of Pediococcus spp. (25 P. acidilactici, 9 P. pentosaceus, and 2 P. urinaeequi strains). Penicillin G, imipenem, gentamicin, netilmicin, erythromycin, clindamycin, rifampin, chloramphenicol, daptomycin, and ramoplanin were the most active. All strains of P. acidilactici were susceptible to novobiocin, whereas all isolates of P. pentosaceus were resistant. Novobiocin could therefore be helpful for differentiation of these two closely related species. P. acidilactici HM3020 was inducibly resistant to macrolide, lincosamide, and streptogramin B type (MLS) antibiotics. Resistance was due to a determinant homologous to ermAM and carried by a nontransferable 46-kb plasmid, pVM20. This plasmid was structurally distinct from two enterococcal MLS resistance plasmids, pIP819 and pAM beta 1. The 34 strains of P. acidilactici and P. pentosaceus were resistant to tetracycline, and total DNA of these strains did not hybridize to probes specific for tetK, tetL, tetM, and tetO. PMID- 8494377 TI - In vitro and in vivo antichlamydial activities of newly developed quinolone antimicrobial agents. AB - The in vitro and in vivo activities of three newly developed quinolone antimicrobial agents (sparfloxacin, tosufloxacin, and OPC-17116) were investigated. All three agents showed potent in vitro activities against Chlamydia psittaci, C. trachomatis, and C. pneumoniae with MICs that ranged from 0.031 to 0.125 micrograms/ml. These values were higher than those of minocycline (0.0075 to 0.015 micrograms/ml) but lower than those of erythromycin (0.25 to 0.5 micrograms/ml) and ofloxacin and ciprofloxacin (0.5 to 1.0 micrograms/ml). Mice were challenged with 10(5) inclusion-forming units of C. psittaci each by nasal instillation. All untreated control animals died within 7 days. The survival rates of mice treated with 40 mg of sparfloxacin, OPC-17116, or tosufloxacin per kg of body weight every 12 h for 7 days were 73, 73, and 60%, respectively, 7 days after the challenge. The survival rate of mice treated with ofloxacin at the same dosage was 53%. On the basis of the above results, we concluded that these three new quinolones might be useful in the treatment of chlamydial respiratory infections. PMID- 8494378 TI - Ecology of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva and effects of antibiotics on their distribution in patients with lower respiratory tract infections. AB - Nine patients with lower respiratory tract infections were used to study in detail the effect of ampicillin or erythromycin on the colonization patterns of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva. H. influenzae was isolated from purulent sputum of eight patients before the start of treatment. Ampicillin was more effective than erythromycin at clearing H. influenzae from sputum and in decreasing purulence. By careful characterization of multiple strains, the changes in biotype distribution and antibiotic susceptibility patterns were shown. Five biotypes of H. influenzae were associated with chest infection, with type II predominating. Mixed biotype infections occurred in five patients. Most saliva contained multiple biotypes of H. parainfluenzae. Neither antibiotic selected resistant haemophili in saliva or sputum. After treatment with ampicillin, the mucoid sputum was colonized with ampicillin-susceptible H. parainfluenzae biotypes previously found in saliva. We postulate that as inflammation decreases at the bronchial mucosa, the ampicillin concentration drops, allowing ampicillin-susceptible oral H. parainfluenzae isolates to seed the residual mucoid sputum. PMID- 8494379 TI - In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine. AB - Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4 phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in target CD4+ ATH8 cells, the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively. Both agents completely blocked the replication of 3'-azido-2',3'-dideoxythymidine-sensitive and -insensitive clinical HIV-1 isolates at 0.08 microM as tested in target phytohemagglutinin-activated peripheral blood mononuclear cells. The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI 272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells. Both compounds blocked the posttranslational cleavage of the p55 precursor protein to generate the mature p24 Gag protein in stably HIV-1 infected cells. The n-octanol-water partition coefficients of KNI-227 and KNI-272 were high, with log Po/w values of 3.79 and 3.56, respectively. Degradation of KNI-227 and KNI-272 in the presence of pepsin (1 mg/ml, pH 2.2) at 37 degrees C for 24 h was negligible. Current data warrant further careful investigations toward possible clinical application of these two novel compounds. PMID- 8494380 TI - Comparative pharmacokinetics of two prodrugs of zidovudine in rabbits: enhanced levels of zidovudine in brain tissue. AB - The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3 [(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model to determine their potential utility as drugs against human immunodeficiency virus. Drugs were administered by intravenous infusion over 5 min at doses equal to 10 mg of AZT per kg of body weight. The levels of the prodrugs and of released AZT in plasma, cerebrospinal fluid (CSF), and brain were determined by high-performance liquid chromatography analysis. DPAZT disappeared rapidly from plasma, whereas IAZT maintained a sustained level in plasma for up to 4 h. The levels in plasma of AZT released from DPAZT were consistently lower than the levels of AZT released from IAZT or AZT itself. At 75 min after infusion of AZT, DPAZT, and IAZT, the CSF plasma AZT ratios were 0.23, 0.30, and 0.25, while the brain/CSF AZT ratios were 0.32, 0.63, and 0.64, respectively. These results indicate that the administration of each of the prodrugs produced a higher concentration of AZT in the brain than did the direct administration of AZT. Both prodrugs therefore may be superior to AZT itself with respect to achieving anti-human immunodeficiency virus concentrations within the central nervous system. PMID- 8494381 TI - Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein. AB - The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents. Mean alpha CD4-PAP IC50s were 48 x 10(-3) nM (range, 0.02 x 10(-3) to 212 x 10(-3) nM) for isolates from zidovudine-untreated individuals, and 16 x 10(-3) nM (range, 2 x 10(-3) to 28 x 10(-3) nM) for isolates from treated patients. Overall, higher concentrations of alpha CD4-PAP were necessary to inhibit HIV-1 strains from untreated individuals at more advanced stages of disease. Seventeen isolates were susceptible to zidovudine (mean IC50, 117 nM), and five were resistant to zidovudine (mean IC50, 3,724 nM). Mean alpha CD4-PAP IC50s were 43 x 10(-3) nM for zidovudine susceptible isolates and 19 x 10(-3) nM for isolates resistant to zidovudine. All HIV-1 strains had IC50s greater than 0.5 nM for unconjugated PAP, the alpha CD19 PAP immunoconjugate, and monoclonal antibody alpha CD4. At concentrations as high as 5,000 nM, alphaCD4-PAP did not inhibit colony formation by normal bone marrow progenitor cells(BFU-E, CFU-GM , and CFU-GEMM) or myeloid cell lines (KG-1 and HL 60) and did not decrease cell viabilities of T-cell (Jurkat) or B-cell (FL-112 and Raji) precursor lines. Overall, alphaCD4-PAP demonstrated more potent anti HIV-1 activity than zidovudine and inhibited replication of zidovudine susceptible and zidovudine-resistant viruses at concentrations that were not toxic to lymphohematopoietic cell populations. PMID- 8494382 TI - Comparative efficacies of ofloxacin, cefotaxime, and doxycycline for treatment of experimental epididymitis due to Escherichia coli in rats. AB - The in vivo efficacy of ofloxacin was compared with those of cefotaxime and doxycycline in a rat model of epididymitis due to Escherichia coli. Treatment was started 24 h after infection and was continued for 7 days. Ofloxacin reduced the numbers of E. coli organisms in the epididymides significantly more than the other therapeutic regimens and cured the infection more frequently. Histopathological changes in the epididymides of ofloxacin-treated animals were significantly less severe than those observed in untreated animals. Doxycycline was less effective than ofloxacin but significantly reduced the titers of organisms in rat epididymides. In contrast, despite excellent in vitro activity, cefotaxime failed to reduce the magnitude of infection. The results of this study suggest that ofloxacin may be a very effective antimicrobial agent for the treatment of epididymitis due to E. coli. PMID- 8494383 TI - 2-substituted quinoline alkaloids as potential antileishmanial drugs. AB - Ten 2-substituted quinoline alkaloids isolated from a plant used for treatment of New World cutaneous leishmaniasis have antileishmanial in vitro activities against the extracellular forms of Leishmania spp. BALB/c mice infected with Leishmania amazonensis PH8 or H-142 or Leishmania venezuelensis were treated 1 day after the parasitic infection with a quinoline alkaloid (100 mg/kg of body weight per day) or with reference drug N-methylglucamine antimonate (Glucantime) (56 mg of pentavalent antimony [Sbv] per kg per day) for 14 days. Lesion development was the criterium used to assess disease severity. Two three-carbon chain quinolines [2-n-propylquinoline and 2-(1',2'-trans-epoxypropyl)quinoline (chimanine D)] were more potent than N-methylglucamine antimonate against L. amazonensis PH8, and five quinoline alkaloids [2-(3,4 methylenedioxyphenylethyl)quinoline, cusparine, 2-(3,4 dimethoxyphenylethyl)quinoline, 2-(E)-prop-1'-enylquinoline (chimanine B), and skimmianine] were as effective as the reference drug. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 2-n propylquinoline or chimanine B reduced the severity of lesions but less notably than N-methylglucamine antimonate. 2-n-Propylquinoline exhibited significant activity against the virulent strain L. venezuelensis. The active products did not show any apparent toxicities during the experiment. This study is, to our knowledge, the first to show the activity of 2-substituted quinoline alkaloids for experimental treatment of New World cutaneous leishmaniasis. Further investigations of these compounds might yet prove helpful for the development of new antileishmanial drugs. PMID- 8494384 TI - Clarithromycin therapy of experimental Treponema pallidum infections in hamsters. AB - Clarithromycin was shown to be effective therapy for Treponema pallidum infections in hamsters. Clarithromycin therapy was effective when initiated either 1 or 8 days after infection. The delay in initiation of therapy allowed an active infection to develop. The treponemal burden in lymph tissue of treated hamsters was eradicated, as determined by dark-field microscopy and by inoculation of lymph material into susceptible hamsters. Treatments with clarithromycin and the 14-hydroxy metabolite of clarithromycin were equally effective. Therapy with clarithromycin and penicillin was not antagonistic and did not appear to be synergistic when the two drugs were given concurrently. Pharmacokinetic evaluation of clarithromycin in hamsters showed that the doses which produced effective therapy yielded concentrations in serum similar to those routinely achieved in human sera. These findings demonstrate that clarithromycin is effective in treating active or incubating syphilis in the hamster model and could be useful in treating humans. PMID- 8494385 TI - In vitro antimicrobial susceptibilities of Nocardia species. AB - The in vitro activities of various quinolones, two new aminoglycosides, a new cephamycin analog (cefmetazole) and a new spectinomycin analog (trospectomycin), imipenem, and trimethoprim-sulfamethoxazole against 26 isolates of Nocardia asteroides, 7 isolates of N. brasiliensis, and 6 isolates of N. caviae were determined by a broth microdilution method. The three new quinolones, PD 117558, PD 117596 and PD 112739, inhibited 90% of N. asteroides at 1 to 2 micrograms/ml, and two new aminoglycosides, SCH 21420 and SCH 22591, inhibited 90% of N. asteroides at 2 to 4 micrograms/ml. Among the beta-lactams, cefmetazole was more active than imipenem. N. brasiliensis and N. caviae isolates were also very susceptible to the three quinolones (MICs for 50% of the isolates, 0.25 to 1 microgram/ml) and the two aminoglycosides (MICs for 50% of the isolates, 1 to 2 micrograms/ml). Cefmetazole was moderately active against N. brasiliensis, whereas imipenem showed poor activity against both of these species. PMID- 8494386 TI - Curative and preventive anticryptosporidium activities of sinefungin in an immunosuppressed adult rat model. AB - An immunosuppressed rat model was used to investigate the anti-Cryptosporidium parvum activity of sinefungin. In infected animals, oral sinefungin therapy resulted in a dose-related suppression of oocyst shedding, which correlated with oocyst disappearance from ileal sections. When administered prior to or on the day of oocyst challenge, sinefungin successfully prevented infection. These data suggest that sinefungin could be considered as a candidate molecule in the treatment of human cryptosporidiosis, considered to be the most significant enteric opportunistic infection in AIDS. PMID- 8494387 TI - Antimicrobial activity and disk diffusion susceptibility testing of Ro 40-6890, the active metabolite of the new cephalosporin ester, Ro 41-3399. AB - Ro 40-6890, the active metabolite of Ro 41-3399, was tested against 391 gram negative and gram-positive clinical isolates. Ro 40-6890 was active against members of the family Enterobacteriaceae, Moraxella catarrhalis, pneumococci, other Streptococcus spp., and methicillin-susceptible staphylococci. Preliminary disk diffusion interpretive zone criteria were calculated for 5-, 10-, and 30 micrograms Ro 40-6890 disks and several possible MIC susceptibility breakpoints. We recommend the use of the 5-micrograms disk and suggest that the following zone diameters be used as breakpoints in clinical trials: susceptible, > or = 21 mm (MIC, < or = 1 microgram/ml); intermediate, 18 to 20 mm (MIC, 2 micrograms/ml); and resistant, < or = 17 mm (MIC, > or = 4 micrograms/ml). PMID- 8494388 TI - In vitro activities of ramoplanin, selected glycopeptides, fluoroquinolones, and other antibiotics against clinical bloodstream isolates of gram-positive cocci. AB - The susceptibilities of 316 gram-positive bacteremic isolates to ramoplanin, vancomycin, and teicoplanin and seven other antibiotics were tested. Ramoplanin demonstrated MICs of < or = 0.25 microgram/ml for at least 99% of Staphylococcus aureus isolates and 100% of coagulase-negative staphylococci tested. For both oxacillin-susceptible and oxacillin-resistant S. aureus and coagulase-negative staphylococci, the activity of ramoplanin surpassed those of both vancomycin and teicoplanin. Ramoplanin and teicoplanin had comparable activities against enterococci and Streptococcus pneumoniae and were superior to vancomycin. PMID- 8494389 TI - In vitro susceptibilities of tropical strains of Aeromonas species from Queensland, Australia, to 22 antimicrobial agents. AB - Greater than 90% of 131 strains of Aeromonas species were susceptible to the aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, aztreonam, quinolones, tetracycline, and chloramphenicol, and all were uniformly resistant to ampicillin. Except for amoxicillin-clavulanate, sulfonamide, trimethoprim, and trimethoprim-sulfamethoxazole, there was good correlation between the results obtained by the agar dilution and disk diffusion techniques. PMID- 8494390 TI - In vitro activity of RP 74501-RP 74502, a novel streptogramin antimicrobial mixture, against clinical isolates of Legionella species. AB - Agar and broth microdilution MICs of RP 74501-RP 74502, a mixture of streptogramin antimicrobial agents that inhibited 90% of 22 Legionella strains tested, were 0.64 and 0.08 microgram/ml, respectively; respective erythromycin values were 1.0 and 0.12 microgram/ml. RP 74501-RP 74502 at 1 microgram/ml was more active than the same erythromycin concentration in a macrophage system for both L. pneumophila strains studied but at a lower concentration (0.25 microgram/ml) was much less active than erythromycin. PMID- 8494391 TI - In vitro activities of new macrolides and rifapentine against Brucella spp. AB - We have tested the in vitro activities of streptomycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, erythromycin, four new macrolides (roxithromycin, azithromycin, clarithromycin, and dirithromycin), and rifapentine against 62 strains of Brucella spp. Azithromycin and clarithromycin were, respectively, eight- and twofold more active than erythromycins (MIC for 90% of strains = 2, 8, and 16 micrograms/ml, respectively). The activity of rifapentine was similar to that of rifampin (MIC for 90% of strains = 1 microgram/ml). PMID- 8494392 TI - Kill kinetics and regrowth patterns of Escherichia coli exposed to gentamicin concentration-time profiles simulating in vivo bolus and infusion dosing. AB - The relative influence of peak concentration (Cmax) versus the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 was studied. Bacteria in the lag phase were exposed to an in vitro gentamicin concentration series which mirrored the concentrations determined in patients after 80-mg intravenous bolus (1 min) and 80-mg intravenous infusion (30 min) doses. Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure. Both the Cmax and AUC were shown to be factors determining antibacterial activity; however, the Cmax was an independent determinant of effect. These findings indicate that bolus intravenous dosing with gentamicin could maximize bactericidal activity. Increased efficacy could result at any given daily antibiotic dose if delivered via bolus with long intervals (12 to 24 h) between doses if appropriate precautions to avoid toxicity are taken. PMID- 8494393 TI - Effects of subinhibitory concentrations of vancomycin and teicoplanin on adherence of staphylococci to tissue culture plates. AB - Bacterial adhesion is the first step in infection of medical devices. Staphylococcus aureus and Staphylococcus epidermidis are the pathogens recovered most often. The effects of subinhibitory concentrations of vancomycin and teicoplanin on the adherence of eight clinical strains of S. aureus and eight strains of S. epidermidis to tissue culture plates in vitro were tested. The mean relative inhibitions of adherence at one-fourth and one-eighth the MIC were statistically different for teicoplanin and vancomycin. Slime production seemed not to be involved in adherence. PMID- 8494394 TI - In vitro activity of cycloguanil against African isolates of Plasmodium falciparum. AB - The in vitro activity of cycloguanil was assessed against 86 African isolates of Plasmodium falciparum by a semi-micro assay system. A bimodal distribution of susceptibility patterns was observed, with 44% of the isolates being cycloguanil susceptible. Cycloguanil alone retains a high activity against the intraerythrocytic forms of some isolates and, together with its activity against the hepatic stages, may be useful for chemoprophylaxis when combined with chloroquine. PMID- 8494395 TI - Anti-infective agents, biologics, and vaccines approved by the U.S. Food and Drug Administration in 1992. PMID- 8494396 TI - Nomenclature of aminoglycoside resistance genes: a comment. PMID- 8494397 TI - Multidimensional analysis for interpreting antibiotic susceptibility data. PMID- 8494398 TI - Rational suicide among older adults: a cause for concern? AB - Society is collectively having to examine questions it has never had to face before and nurses are frequently confronted with the difficult issue of whether suicide can or should be a rational choice for older adults. They may be faced with the question of whether an older person should ever be restrained from suicide. Arguments for and against rational suicide are highlighted and the author makes the case for a rational approach to the affirmation of life, rather than its rejection, even to the very end. PMID- 8494399 TI - Letter from China (no. 2) PMID- 8494400 TI - "Empowerment" and the abuse of power. PMID- 8494401 TI - The Milieu Enhancement Model: a nursing practice model, Part I. AB - The Milieu Enhancement Nursing Practice Model (MEM) served as the conceptual framework for implementing a 3-year project funded by the Department of Health and Human Services through the Division of Nursing as a demonstration grant (No. 1 D10 NU 600013) from October 1987 through September 1990. The MEM is described and examples of its use in developing health care forms, conducting research, guiding practice, and categorizing enhancements are presented. PMID- 8494402 TI - The cost-effectiveness of a nursing demonstration project, Part II. AB - The Milieu Enhancement Project was funded for 3 years by the Division of Nursing, Department of Health and Human Services. The goals, setting, project personnel, roles, and implementation activities are described. This project allowed faculty and graduate students to practice independently in a children's residential setting. A needs assessment identified problems related to organizational, academic, and sex- and health-related concerns. These concerns were addressed and outcome measurements identified. A cost-effectiveness framework was used to describe the interventions in terms of improvement. Statistical analyses supported the effectiveness of several project activities. PMID- 8494403 TI - The cost-benefits of a nursing demonstration project, Part III. AB - The Milieu Enhancement Nursing project was funded for 3 years by the Division of Nursing, Department of Health and Human Services. One of the project goals was to perform a cost/benefit analysis of project activities. The conceptual framework and formulas used for data analysis are presented. The project was deemed successful, as data supported a favorable cost to benefit ratio. PMID- 8494404 TI - Characterizing the neuropsychological functioning of persons with human immunodeficiency virus infection, Part I. Acquired immunodeficiency syndrome dementia complex: a review. AB - The findings of studies that use psychoneuroimmunological frameworks can help nurses evaluate and treat patients' psychological and physical responses to infection with the human immunodeficiency virus (HIV). One response to HIV infection, acquired immunodeficiency syndrome (AIDS) dementia complex (ADC), may occur at any stage of the infection and is particularly distressing to both patients and nurses. In Part I of this series, current research pertinent to ADC is reviewed. In Part II, we describe an approach used to characterize the neuropsychological functioning of persons at different stages of HIV infection. PMID- 8494405 TI - Characterizing the neuropsychological functioning of persons with human immunodeficiency virus (HIV) infection, Part II. Neuropsychological functioning of persons at different stages of HIV infection. AB - Neuropsychological impairment has been reported to occur in persons at all stages of infection with the human immunodeficiency virus (HIV). However, the findings of studies to characterize the incidence and pattern of impairment have been limited by inconsistent definitions of impairment and the failure to control for confounding variables, such as hematological abnormalities, history of head injury, or substance abuse. In the present study, neuropsychological tests were administered to 141 persons at four stages of HIV infection. Significant differences were found in the percentage of persons who showed impairment at each stage of infection. Further, participants' performance on the tests tended to decline across progressive stages of infection. These findings may help psychiatric nurses identify and manage the changes associated with HIV infection. PMID- 8494406 TI - Reminiscence and life review: explaining the differences. AB - Although the terms reminiscence and life review continue to be used interchangeably in the literature, they are separate interventions. This article describes the differences, similarities, and commonalities in these two nursing interventions by highlighting differences in goals, theory base, the nurse's role, and the client's role. The implementation process and the desired outcomes are also differentiated to move forward nurse's understanding of these two important nursing interventions. PMID- 8494407 TI - Psychosocial health needs of older women: urban versus rural comparisons. AB - The population of older women who live alone is rapidly expanding. For a variety of reasons, mental health needs often are not treated. A stress-coping framework guided this study of psychosocial health needs in both urban and rural women. Urban women reported higher levels of stress and greater use of community services. Forty-two percent of the total group of women reported that they had either used psychotropic drugs or felt a need for them and, yet only 2% had ever used outpatient mental health services. Implications for nurses are discussed. PMID- 8494408 TI - In memoriam: Nina S. Braunwald, 1928-1992. PMID- 8494409 TI - And it happened during our lifetime... PMID- 8494410 TI - Epiphrenic diverticula: fact and fable. PMID- 8494411 TI - Steroid-free heart transplantation: an analysis. PMID- 8494412 TI - Warm blood cardioplegia: benefits and risks. PMID- 8494413 TI - Effect of inflation on adenosine triphosphate catabolism and lactate production during normothermic lung ischemia. AB - Although few biochemical data comparing adenosine triphosphate (ATP) catabolism or lactate production in isolated deflated versus inflated lung tissue are available, most transplant centers preserve their donor lungs inflated. We measured ATP level (using high-performance liquid chromatography), energy charge, and lactate level during 2 hours of normothermic ischemia in deflated lung tissue (n = 6), in lung tissue inflated with room air (n = 6), and in lung tissue inflated with 100% oxygen (n = 6). To determine the onset of anaerobic metabolism in lung tissue inflated with 100% O2, ATP and lactate levels were measured in another group (n = 6) during 8 hours of normothermic ischemia. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 mL/kg). They were isolated and immersed in 0.9% NaCl at 37 degrees C. In deflated lung tissue, ATP level (control value, 9.4 +/- 0.58 mumol/g dry wt) decreased and lactate level (control value, 5.6 +/- 1.16 mumol/g dry wt) increased after 15 minutes of ischemia (ATP, 5.2 +/- 0.86 mumol/g dry wt; lactate, 13.3 +/- 1.58 mumol/g dry wt). When the lung was stored inflated with room air, ATP breakdown and increase of lactate concentration only occurred after 90 minutes of normothermic ischemia (at 60 minutes: ATP, 8.0 +/- 0.58 mumol/g dry wt; lactate, 6.3 +/- 1.1 mumol/g dry wt). In lungs stored inflated with 100% O2, ATP breakdown and lactate accumulation only occurred after 5 hours of normothermic ischemia (at 4 hours: ATP, 8.1 +/- 0.74 mumol/g dry wt; lactate, 5.9 +/- 1.28 mumol/g dry wt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494414 TI - Cardiopulmonary bypass impairs small intestinal transport and increases gut permeability. AB - Gastrointestinal damage occurs in 0.6% to 2% of patients after cardiopulmonary bypass (CPB), and carries a mortality of 12% to 67%. The incidence of subclinical gastrointestinal damage may be much greater. We examined the effects of nonpulsatile, hypothermic CPB on intestinal absorption and permeability in 41 patients. Bowel mucosal saccharide transport and permeation were evaluated using 100 mL of an oral solution containing 3-O-methyl-D-glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and lactulose (5.0 g) to assess active carrier-mediated, passive carrier-mediated, transcellular, and paracellular transport, respectively, with a 5-hour urine analysis. Patients were studied before, immediately after, and 5 days after CPB. Immediately after CPB there was a decrease in urinary excretion of 3-O-methyl-D-glucose (from 34% +/- 2.2% to 5.2% +/- 0.7%; p < 0.0001), D-xylose (from 25.4% +/- 1.4% to 4.1% +/- 0.8%; p < 0.0001), and L-rhamnose (from 8.3% +/- 0.6% to 2.6% +/- 0.4%; p < 0.0001). The permeation of 3-O-methyl-D-glucose and D-xylose returned to normal levels 5 days after CPB, but that of L-rhamnose remained significantly below pre-CPB values at 6.6% +/- 0.5% (p = 0.004). However, the permeation of lactulose increased after CPB (from 0.35% +/- 0.04% to 0.59% +/- 0.1%; p = 0.018), and the lactulose/L rhamnose gut permeability ratio increased markedly (from 0.045 +/- 0.04 to 0.36 +/- 0.08; normal = 0.06 to 0.08; p = 0.004). Patients who had a CPB time of 100 minutes or more had a greater increase in gut permeability (p = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494415 TI - Double-lung transplantation in mechanically ventilated patients with cystic fibrosis. AB - Many lung transplant programs consider ventilator dependence as a contraindication for transplantation. Among 54 patients in whom bilateral lung transplantations for cystic fibrosis were performed by the Joint Marseille Montreal Lung Transplant Program, 10 were ventilator dependent. Three of them died in the early postoperative period (30%): 2 as a result of cerebral anoxia and sepsis, 1 of Pseudomonas cepacia pneumonia. Two patients died at 15 and 19 months after transplantation of obliterative bronchiolitis and secondary bacterial pneumonitis. Another 2 patients in whom obliterative bronchiolitis developed underwent retransplantation with a heart-lung block; 1 of those was operated on at 12 months and is well at 29 months after his initial transplantation; the second was operated on at 34 months and died of primary graft failure. Three other patients are alive and well at 3, 11, and 14 months after transplantation. Actuarial survival at 1 year was 70%. The postoperative course and the infectious and rejection complications were no different from those in patients who underwent transplantation while spontaneously breathing. Obliterative bronchiolitis developed in 66% of patients at risk (2 of 6 patients surviving more than 6 months). We conclude that transplantation in mechanically ventilated patients with cystic fibrosis is not associated with an increase in morbidity or mortality after bilateral lung transplantation. Long-term survival, as in patients who undergo transplantation while spontaneously breathing, is limited by the development of obliterative bronchiolitis. PMID- 8494416 TI - Effects of pH on brain energetics after hypothermic circulatory arrest. AB - The pH management that provides optimal organ protection during hypothermic circulatory arrest is uncertain. Recent retrospective clinical data suggest that the pH-stat strategy (maintenance of pH at 7.40 corrected to core temperature) may improve brain protection during hypothermic cardiopulmonary bypass with a period of circulatory arrest in infants. The impact of alpha-stat (group A) and pH-stat (group P) strategies on recovery of cerebral high-energy phosphates and intracellular pH measured by magnetic resonance spectroscopy (A, n = 7; P, n = 5), organ blood flow measured by microspheres, cerebral metabolic rate measured by oxygen and glucose extraction (A, n = 7; P, n = 6), and cerebral edema was studied in 25 4-week-old piglets undergoing core cooling and 1 hour of circulatory arrest at 15 degrees C. Group P had greater cerebral blood flow during core cooling (54.3% +/- 4.7% versus 34.2% +/- 1.5% of normothermic baseline, respectively; p = 0.001). The intracellular pH during core cooling showed an alkaline shift in both groups but became more alkaline in group A than in group P at the end of cooling (7.08 to 7.63 versus 7.09 to 7.41, respectively; p = 0.013). Recovery of cerebral adenosine triphosphate (p = 0.046) and intracellular pH (p = 0.014) in the initial 30 minutes of reperfusion was faster in group P. The cerebral intracellular pH became more acidotic during early reperfusion in group A, whereas it showed continuous recovery in group P. Brain water content postoperatively was less in group P (0.8075) than in group A (0.8124) (p = 0.05). These results suggest that compared with alpha-stat, the pH stat strategy provides better early brain recovery after deep hypothermic cardiopulmonary bypass with circulatory arrest in the immature animal. Possible mechanisms include improved brain cooling by increased blood flow to subcortical areas, improved oxygen delivery, and reduction of reperfusion injury, as well as an alkaline shift in intracellular pH with hypothermia in spite of a stable blood pH. PMID- 8494417 TI - Cardiopulmonary bypass in HIV-positive patients. AB - To prove the hypothesis that cardiopulmonary bypass may accelerate the development of acquired immunodeficiency syndrome (AIDS) in the human immunodeficiency virus carrier, the clinical course of 40 patients positive for human immunodeficiency virus who underwent cardiac operations between 1986 and 1992 was analyzed, especially in regard to the progression to AIDS. Mean age was 30 years (range, 19 to 61 years). Thirty-four patients (85%) were intravenous drug abusers; in 4 (10%) transmission of infection was sexual, and in 2 (5%) it was through a contaminated blood transfusion. Valve procedures were performed in 38 patients (95%), mostly for endocarditis in drug addicts. Hospital mortality was 20% (8 patients). The 32 survivors have been followed up a mean of 21 months (range, 4 months to 6 years). Four patients (12.5%) experienced progression to AIDS during the follow-up period. Actuarial progression to AIDS is 5% (+/- 5%) at 1 year, 20% (+/- 10%) at 2 years, and 40% (+/- 19%) at 5 years. There have been 8 late deaths (5 due to recurrent endocarditis, 2 due to AIDS, and 1 due to overdose). Actuarial survival is 79% (+/- 8%) at 1 year, 60% (+/- 11%) at 2 years, and 48% (+/- 14%) at 5 years. The results indicate that progression to AIDS in the patient positive for human immunodeficiency virus is not accelerated by the use of cardiopulmonary bypass. The poor prognosis in these patients is mainly related to the particular pathological conditions that often affect the drug addict population. PMID- 8494418 TI - Epiphrenic diverticulum: results of surgical treatment. AB - From 1975 to 1991, 112 patients (64 men and 48 women) were found to have an epiphrenic diverticulum. Symptoms were absent or minimal in 71 patients and incapacitating in 41. All patients with minimal symptoms were managed conservatively; 35 were available for follow-up, which ranged from 1 to 25 years (median, 9 years). None of these 35 patients had clinically significant progression of symptoms. Surgical repair was done in 33 patients with incapacitating symptoms. Achalasia was present in 8 of the surgical patients (24.2%), diffuse esophageal spasm in 3 (9.1%), hypertensive lower esophageal sphincter alone in 1 (3.0%), and nonspecific motor abnormalities of the esophageal body in 7 (21.2%). Diverticulectomy and esophagomyotomy were performed in 22 patients, diverticulectomy alone in 7, esophageal resection in 3, and esophagomyotomy alone in 1. Concomitant hiatal hernia repair was done in 6 patients. Complications occurred in 11 patients; 6 had esophageal leaks. There were three operative deaths (9.1%), all occurring in patients with abnormal manometry. Follow-up was complete in 29 patients and ranged from 4 months to 15 years (median, 6.9 years). Long-term results were excellent in 14 patients (48.2%), good in 8 (27.6%), fair in 5 (17.2%), and poor in 2 (6.9%). We conclude that operation has significant risks and is not warranted in patients with minimal symptoms because progression is unlikely. Surgical treatment, however, is advisable in patients with incapacitating symptoms because most operative survivors will have long-term symptomatic palliation. PMID- 8494419 TI - Intrapleural doxycycline control of malignant pleural effusions. AB - The intrapleural instillation of agents for pleural sclerosis has proved effective in preventing the reaccumulation of symptomatic malignant pleural effusions. Because manufacture of the most popular agent, tetracycline, was recently discontinued, a preliminary study was undertaken to evaluate an alternative agent, doxycycline, for treating symptomatic malignant pleural effusions. From November 1991 to September 1992, 21 patients with symptomatic malignant pleural effusions have undergone overnight chest tube drainage followed by intrapleural instillation of 10 mL 1% lidocaine and then doxycycline, 500 mg in 30 mL 0.9% saline solution. The chest tube was clamped 2 hours with patient repositioning every 15 minutes. Tubes were removed when drainage was less than 50 mL/8 h. Of surviving patients, a complete objective response at 1 month was obtained in 88% (15/17), who were free of a symptomatic or radiographic recurrence of the effusion. Complications included mild pain in 23% (5/21), moderate pain requiring analgesics in 19% (4/21), and mild fever in 5% (1/21). There were no treatment-related deaths. The mean time for chest tube removal was 1.7 +/- 0.7 days after the last treatment. Based on this preliminary study, we conclude that doxycycline is a highly effective agent for the palliative treatment of symptomatic malignant pleural effusions. Its safety profile and efficacy compare favorably with those of tetracycline and other agents used for pleural sclerosis. PMID- 8494420 TI - Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution. AB - Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketoglutarate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours. PMID- 8494421 TI - University of Wisconsin versus St. Thomas' Hospital solution for human donor heart preservation. AB - Prolongation of the safe period of ischemia of the heart is an efficient way to overcome donor organ shortage, as demonstrated in renal and hepatic transplantation. We present the results of a prospective, randomized study comparing preservation with University of Wisconsin solution (UWS) versus St. Thomas' Hospital solution (STS) in clinical heart transplantation. A total of 39 patients were enrolled in the study (n = 20 for UWS and n = 19 for STS). Hemodynamic, electron microscopic, and biochemical evaluation did not reveal any significant differences in postoperative myocardial performance. Only the number of intraoperative defibrillations (0.82 for UWS versus 1.7 for STS) and the rhythm stability after reperfusion (13/20 UWS hearts versus 6/19 STS hearts in sinus rhythm) were significantly different. Heart preservation with UWS and STS appears to be of comparable efficacy at mean ischemic times of less than 4 hours. PMID- 8494422 TI - Repair of atrial septal defect through a right thoracotomy. AB - Fifty-four patients underwent repair of atrial septal defects through a right thoracotomy between January 1985 and December 1991. The average patient was 5.7 years old. Defects repaired included 51 secundum, 2 sinus venosus, and 1 ostium primum defect. The average bypass time was 24 minutes. There was no operative or late mortality, and no morbidity directly related to the thoracotomy approach. The right thoracotomy incision is a safe and effective alternative to a median sternotomy for repair of atrial septal defects. The cosmetic result is superior to that of median sternotomy or bilateral submammary incision. PMID- 8494423 TI - Left ventricular assist with an axial flow pump (Hemopump): clinical application. AB - Eighteen patients suffering from acute left heart failure were selected as candidates for Hemopump support. In 6 patients, peripheral atheromatosis prevented insertion of the device. Of the remaining 12 patients, 9 had postcardiotomy shock, 2 had acute rejection after orthotopic heart transplantation, and 1 had acute myocardial infarction complicated by a large postinfarction ventricular septal defect. During Hemopump support, hemodynamics recovered in all patients. Major complications were related to mechanical pump failure, such as fracture of the drive cable and expulsion of the cannula out of the ventricle, or to hemolysis of variable degree. Seven patients (58%) survived and were discharged from the hospital: the 2 patients bridged to heart transplantation and 5 of the 9 postcardiotomy patients, including 1 who could not be weaned but later underwent successful transplantation. The patient with the postinfarction ventricular septal defect died after removal of the device because of hemolysis. These results indicate that the Hemopump is a relatively noninvasive and efficacious left ventricular system of moderate power. PMID- 8494424 TI - Increased lung injury in pulmonary hypertensive patients during open heart operations. AB - To investigate lung injury in adult open heart operations during extracorporeal circulation, we measured plasma chemiluminescence levels. Nineteen patients were divided into two groups depending on preoperative pulmonary artery pressure: a pulmonary hypertension group (n = 11) and a control group (n = 8). Plasma samples were taken simultaneously from arterial and central venous lines at six different points during and early after operation. Arteriovenous difference of chemiluminescence (counts/10 seconds) increased significantly only in the pulmonary hypertension group (from -19.1 +/- 8.3 at the end of cross-clamping to 23.7 +/- 12.4 at the end of bypass; p < 0.01). There was a positive correlation between peak values of arterial plasma chemiluminescence and postoperative respiratory index in the pulmonary hypertension group (p < 0.05). In addition, during the first 12 hours postoperatively, arteriovenous difference of chemiluminescence in the pulmonary hypertension group changed significantly from negative to positive values (p < 0.05). These data suggest that free radical activity (detected by chemiluminescence) was deeply involved in lung injury during and also early after open heart operations, especially in pulmonary hypertensive patients. PMID- 8494425 TI - Noninvasive long-term follow-up after coarctation repair. AB - Thirty patients operated on for aortic coarctation while less than 3 years of age underwent magnetic resonance imaging, digital subtraction angiography, and bicycle exercise testing 14 to 33 years (mean, 22 years) after operation. Diameters of the aorta at the site of the anastomosis, of the distal arch, and of the aorta at the level of the diaphragm were measured in the images. Blood pressures were obtained from the right arm and leg before and after exercise. Patients were divided into three groups according to blood pressure data: group I, resting gradient less than 30 mm Hg and exercise gradient less than 50 mm Hg; group II, resting gradient less than 30 mm Hg and exercise gradient greater than 50 mm Hg; and group III, resting gradient 30 mm Hg or greater. A control group underwent the same test. The frequency of hypertensive patients was greater in groups II (58%) and III (100%) than in group I (20%). The anastomosis/descending aorta ratio seen in digital subtraction angiograms was smaller in group II and III patients. Exercise blood pressure gradient correlated significantly (r = 0.48; p = 0.009) with anastomosis/descending aorta ratio in digital subtraction angiograms but not in magnetic resonance images. Twenty of 30 patients (67%) had a significant anatomic narrowing at the site of the anastomosis. Blood pressure data correlated with diameters measured in digital subtraction angiograms but not with diameters measured in magnetic resonance images. PMID- 8494426 TI - Clinical results of steroid-free induction immunosuppression after heart transplantation. AB - Between January 1987 and September 1991, 112 operative survivors of heart transplantation were initially immunosuppressed with cyclosporin A and azathioprine without prednisone. Eighty-eight patients (79%) remained on a regimen of double therapy for a mean follow-up of 25 +/- 15 months (range, 1 to 54 months), whereas 24 patients (21%) had oral prednisone, 5 mg/day, added to maintenance therapy for persistent or repeated rejection. There were 5 early deaths (4%) because of acute rejection (4 patients) or infection (1 patient). Only 1 patient died late after heart transplantation of chronic rejection. Actuarial survival was 95% +/- 2% and 94% +/- 3% at 12 and 48 months, respectively. Mean rate of acute rejection was 1.7 +/- 1.0 episodes per patient, with a 5% +/- 2% freedom from rejection at 48 months. Ten patients (9%) required in-hospital treatment for infection; the actuarial freedom from infectious episodes was 85% +/- 4% at 48 months. Actuarial freedom from hypertension was 43% +/- 7% at 48 months. At annual catheterization, mean left ventricular ejection fraction was 0.64 +/- 0.08 and 0.62 +/- 0.05 at 1 year and 4 years, respectively, with evidence of coronary lesions in 9 patients (8%). In conclusion, steroid-free immunosuppression after heart transplantation is associated with a high incidence of acute rejection. However, the excellent medium-term survival and the low incidence of both infection and chronic rejection seem to justify a wider use of such treatment. PMID- 8494427 TI - Revised technique of cardiopulmonary bypass in one-stage repair of interrupted aortic arch complex. AB - Twenty infants with interrupted aortic arch associated with various intracardiac anomalies underwent primary complete repair using pulsatile high-flow cardiopulmonary bypass with a short period of circulatory arrest. Age at repair ranged from 11 to 126 days (mean age, 43 days). Weight ranged from 2.2 to 5.5 kg (mean weight, 3.4 kg). Associated cardiac lesions included ventricular septal defect (14 patients), truncus arteriosus (3), transposition of the great arteries (2), and aortopulmonary window (1 patient). Left ventricular outflow tract obstruction was relieved in 2 patients. The aortic arch was reconstructed with a polytetrafluoroethylene graft in 7 patients and by direct anastomosis in the most recent 11 patients. An arterial cannulation method has been devised to facilitate direct anastomosis between the ascending aorta and the descending aorta, to lessen circulatory arrest time, and to prevent dangerous laceration and postoperative narrowing of the thin, small ascending aorta at the cannulation site. Two patients died, a surgical mortality rate of 10%. There has been one late death, which was due to severe truncal valve insufficiency. The other patients are doing well with a mean follow-up of 3 years 6 months. Restenosis of the direct anastomosis has not been noted in any patient. However, subaortic stenosis with pressure gradients of 30 to 40 mm Hg developed in 3 patients. In conclusion, one-stage repair including direct anastomosis for the aortic arch reconstruction and repair of all coexisting intracardiac defects is thought to be the treatment of choice. PMID- 8494428 TI - Intracardiac operation in seven pregnant women. AB - The outcome of open heart operations on pregnant women is not well documented. Between March 1985 and October 1988, 7 pregnant patients underwent valve replacement at Tygerberg Hospital. This included three redo operations and one double-valve replacement. The range of perfusion temperatures used during cardiopulmonary bypass was 28 degrees to 33 degrees C with aortic cross-clamp times of 53 to 121 minutes. One baby was stillborn, but the others were normally delivered at full term, and all the mothers survived. The stillborn baby was lost after the shortest procedure at the highest temperature during cardiopulmonary bypass. PMID- 8494429 TI - Lidocaine prophylaxis in coronary revascularization patients: a randomized, prospective trial. AB - Life-threatening ventricular ectopy can occur after cardiac operations. The actual incidence of ventricular ectopy and the ability to prevent it by the routine prophylactic use of lidocaine hydrochloride have not been established. We performed a double-blind, randomized, prospective trial involving 109 patients undergoing elective coronary artery revascularization. Patients received either lidocaine (n = 54) or a placebo (n = 55) after separation from bypass. A Holter monitor was affixed to each patient for subsequent review, and bedside intensive care monitors with alarms were used for "real-time" surveillance. The code was broken when potentially malignant ventricular ectopy or side effects attributable to the study drug were noted. Three lidocaine patients and 2 placebo patients were dropped from the study because of hemodynamic instability or bleeding. Of the remaining 104 patients, the code was broken in 12 (24%) of the 51 in the lidocaine group (9 for ectopy and 3 for mental status changes) and 10 (19%) of the 53 in the placebo group (all for ectopy) (p = not significant). Twenty-four hour Holter monitor evaluation demonstrated occasional ventricular ectopy in all patients and nonsustained ventricular tachycardia in 28% in the lidocaine group and 48% in the placebo group (p = not significant). The mean number of runs of ventricular tachycardia per patient was 0.53 in the lidocaine group and 1.6 in the placebo group (p = 0.035). There were no significant differences in terms of other ventricular ectopy, morbidity, or mortality. No ventricular fibrillation occurred in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494430 TI - Cadaver lung donors: effect of preharvest ventilation on graft function. AB - The pulmonary donor pool would increase substantially if lungs could be safely transplanted after cessation of circulation. To determine whether ventilation of cadaver lungs could improve graft function, canine donors were sacrificed and then ventilated with 100% oxygen (n = 6) or 100% nitrogen (n = 6); 6 served as nonventilated controls. Four hours after death, the lungs were flushed with modified Euro-Collins solution and harvested. Controls were ventilated with 100% oxygen only during flush and harvest. Recipients were rendered dependent on the transplanted lung by occlusion of the right pulmonary artery and bronchus 1 hour after transplantation. Ventilation was maintained at a constant inspired oxygen fraction of 0.4. Four controls died of pulmonary edema shortly after occlusion of the native lung. The mean arterial oxygen tensions in the oxygen-ventilated, nitrogen-ventilated, and control groups at the end of 8 hours were 81 mm Hg (n = 4), 88 mm Hg (n = 3), and 55 mm Hg (n = 2), respectively. Postmortem oxygen ventilation improved early recipient survival and gas exchange. Postmortem nitrogen ventilation improved early gas exchange and delayed recipient death compared with non-ventilated controls. The mechanics of ventilation appears to confer a functional advantage independent of a continued supply of oxygen. Transplantation of lungs harvested from cadavers after cessation of circulation might be feasible. PMID- 8494431 TI - Massive thymic hyperplasia. AB - Massive thymic hyperplasia is an extremely rare form of true thymic hyperplasia most often described in infants and children. Hyperplasia of this order is not known to occur in any other organ, and its etiology and prognostic significance remain unknown. As there is no accurate way of preoperatively differentiating massive thymic hyperplasia from other tumors of the thymus and anterior mediastinum, we advise excision in all cases for histological analysis and relief of mediastinal compression. This description of 4 cases updates the 30 previously reported cases, and includes a literature review. PMID- 8494432 TI - Should a patient with a treated cancer be offered an open heart operation? AB - The unknown but presumably reduced life expectancy of patients with malignant neoplasms may dissuade surgeons from performing necessary coronary and valvular heart operations. There is also concern for recrudescence of cancer as a result of an impaired immune system after cardiopulmonary bypass. We analyzed the records of 2,190 patients who underwent cardiac operations requiring extracorporeal circulation between 1988 and 1990. Of these, 46 patients had previously been treated for malignancy other than nonmelanoma skin cancer. Open heart operations were performed in patients with cardiac symptoms only in the absence of tumor recurrence. Tumor staging indicated reduced life expectancy in all patients. Thirty-eight patients (82.7%) had myocardial revascularization; 8 patients (17.3%) underwent valve operations. Postoperatively, all but 2 patients were free from complications. In-hospital mortality was 4.3% (2/46). One patient died of cardiogenic shock after combined aortic and mitral valve replacement; the second patient succumbed to pulmonary embolism after reoperative coronary artery bypass grafting. Actuarial survival at 3 years was 96%, and all patients reported a satisfactory quality of life. This experience suggests that cardiac operations in selected patients with previously treated cancer are safe and offer clinical improvement at a reasonable operative risk. PMID- 8494433 TI - Pharmacological relaxation of the saphenous vein during harvesting for coronary artery bypass grafting. AB - Spasm of the saphenous vein frequently occurs during harvesting from the leg and high-pressure distension is required to restore an adequate diameter for grafting. Forceful distention has been shown to damage the intima and media and may predispose to subsequent occlusion of the vein graft. Various pharmacologic vasodilators are capable of relaxing veins; in this study, we carried out a systematic investigation to determine the appropriate agents and concentrations for use during vein graft operations. In organ baths, human saphenous vein segments were contracted with potassium or a thromboxane mimetic, and vasodilator agents were then applied. Glyceryl trinitrate, 7.2 micrograms/mL, or papaverine hydrochloride, 11.9 micrograms/mL, caused 80% to 100% relaxation of contraction induced by potassium or thromboxane. Verapamil, 15.5 micrograms/mL, relaxed the potassium contraction by 100% and the thromboxane contraction by 75%. Comparison of the time course of action showed that glyceryl trinitrate had a rapid onset and a short duration of maximal action, whereas verapamil (like papaverine) had delayed onset and a long duration. A mixture of glyceryl trinitrate and verapamil combined rapid onset with long duration of action. We now use a mixture of glyceryl trinitrate and verapamil (pH 7.4) topically and intraluminally during harvesting of the saphenous vein to provide a relaxed conduit for coronary artery bypass grafting. PMID- 8494434 TI - Hufnagel revisited: a descending thoracic aortic valve to treat prosthetic valve insufficiency. AB - In 1953 Hufnagel and Harvey reported their successful treatment of aortic valve insufficiency by the implantation of a ball-valve prosthesis into the descending thoracic aorta. Since then, great advances in technology, surgery, and anesthesia have made aortic valve replacement a more common procedure with relatively low mortality. This remains true for the vast majority of prosthetic valve replacements. However, cases requiring reoperation can be difficult, leading to a much higher degree of morbidity and mortality. In selected patients who require repeated approaches to the aortic root we propose that Hufnagel's original idea may still be of value to reduce the severity of aortic insufficiency. We report our experience in 4 cases of aortic prosthetic incompetence, all of which were improved by two New York Heart Association functional classes after a modification of Hufnagel's procedure. PMID- 8494435 TI - Surgical techniques in partial anomalous pulmonary veins to the superior vena cava. AB - Over a 12-year period, 40 patients underwent repair of partial anomalous pulmonary veins (PAPV) draining to the superior vena cava (SVC) proximal to the sinus node. Mean age was 6 +/- 2 years. In all patients, the SVC was cannulated superior to the PAPV, which were baffled with pericardium to left atrium. Six patients had associated defects repaired. In 18 patients (group I), an incision was made at the crest of the right atrial appendage (RAA) and extended upward through the sinus node and to the SVC. After rerouting of the PAPV, the SVC was enlarged using the RAA (atriocavoplasty). In 17 patients (group II), rerouting of the PAPV was accomplished through a right atriotomy. Superior vena caval enlargement was not done. Drainage of the PAPV was close to the right atrium in 14 patients (low) and to the azygos vein (high) in 3. In 5 patients (group III), an incision was made on the SVC and RAA sparing the sinus node. After rerouting of the PAPV, the RAA was anastomosed to the SVC (end to side), providing another outlet for SVC flow. There was no early or late death. Two patients (10%) in group I had late sinus bradycardia. Obstruction of the SVC and PAPV developed in 1 patient in group II with high drainage. Intermittent complete heart block developed in 1 patient in group III who also had ventricular septal defect repair. We conclude that atriocavoplasty is effective for rerouting of the PAPV and enlarging the SVC, but may predispose to sinus node disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494436 TI - Warm blood cardioplegia. AB - Between 1990 and 1992, 346 consecutive patients underwent coronary artery bypass procedures. Ninety-eight patients (group A) from 1990 served as historical controls, and 248 patients (group B) from 1991 to 1992 served as a prospective, consecutive cohort for statistical comparison. The two groups varied in the type of myocardial protection used: intermittent cold crystalloid cardioplegia was used in group A and continuous warm blood cardioplegia in group B. (Two patients in group A received intermittent cold blood cardioplegia, and these 2 patients are grouped with the crystalloid group for the sake of convenience. The presence or absence of these 2 patients did not alter the group A statistics in any noticeable manner). Class IV high-risk groups demonstrated a 63% reduction in mortality (p = 0.07), and overall group B experienced a 28% reduction in mortality (4.4% versus 6.1%; p = not significant), an 86% reduction in perioperative myocardial infarction rate (1.6% versus 12.2%; p < 0.05), a 20% reduction in postoperative bleeding (275 versus 345 mL.day-1.m-2), and a marked reduction in reentry rates (p = 0.05). Also noted was a 32% reduction in postoperative ventilation requirements (25 versus 37 hours; p = 0.05). Less inotrope was required and intraoperative stroke was not seen in the patients with warm blood cardioplegia. Group B patients were less likely to have development of complex postoperative arrhythmias. Ventricular fibrillation at unclamping was noticeably rare (2.0% in group B versus 84% in group A; p < 0.05). The average group B heart resumed sinus rhythm 72 seconds after declamping.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494437 TI - Massive descending thoracic aneurysm in a Jehovah's witness: treatment by thromboexclusion. AB - The thromboexclusion technique was used to treat a massive thoracic aneurysm in a Jehovah's witness. Preoperative erythropoietin therapy was used. At operation a Hemashield graft was used to bypass the aneurysm before the mouth was stapled closed. The hemoglobin level fell from 13.5 to 10.6 g/dL. PMID- 8494438 TI - Left ventricular pseudoaneurysm and intracardiac fistulas after replacement of mitral valve prosthesis. AB - Operation was performed on a 61-year-old woman with left ventricular pseudoaneurysm, left ventricular-right atrial fistula, and left ventricular coronary sinus fistula after mitral valve replacement. The diagnostic and therapeutic approaches to these complications are described briefly, and the literature on intracardiac fistula after mitral valve replacement is reviewed. PMID- 8494439 TI - Simple method for cardioplegia retrieval in patients with chronic renal failure. AB - A case in which a retrograde cardioplegia catheter was inserted into the coronary sinus for retrieval of antegrade cardioplegia in a patient with chronic renal failure is described. Potassium levels were maintained within normal limits throughout the procedure. PMID- 8494440 TI - Methyl methacrylate plate to prevent compression after heart transplantation. AB - A methyl methacrylate plate was fashioned to maintain the sternum in the open position in a patient with impaired donor heart function after transplantation. Bilateral mammary flaps enabled soft tissue and skin closure. The chest wall fixation obtained allowed extubation and spontaneous breathing. The plate was subsequently removed. The patient remains well almost 3 years later. PMID- 8494441 TI - Mobile extracorporeal membrane oxygenation. AB - Transport of critically ill neonates in need of extracorporeal membrane oxygenation can be risky. Their extreme cardiorespiratory instability may delay or even preclude conventional transport to an extracorporeal membrane oxygenation center. We report the use of a UH-1 helicopter specially adapted for mobile extracorporeal membrane oxygenation support to transport a critically ill neonate. PMID- 8494442 TI - Rupture of a sinus of Valsalva aneurysm through the tricuspid septal leaflet. AB - We report a case of rupture of an aneurysm of the noncoronary sinus of Valsalva with the tract of the fistula emerging through the tricuspid septal leaflet. This rare pathology created a diagnostic dilemma, as the direction of the jet of blood was alternating between the right atrium and the right ventricle. PMID- 8494443 TI - Intracardiac ectopic thyroid: conservative surgical treatment. AB - The case of a patient with an intracardiac ectopic thyroid is reported. A cardiac tumor was found in a 66-year-old woman and was diagnosed by two-dimensional echocardiography. An intraoperative biopsy was performed, and the mass was recognized as an ectopic thyroid and treated with a conservative surgical approach because of the size, location, and relationship to adjacent structures. The 60-month follow-up shows normal echocardiographic images and the good clinical status of the patient. PMID- 8494444 TI - Unusual location of an atrial myxoma complicated by a secundum atrial septal defect. AB - Myxomas occur most commonly in the left atrium arising from the fossa ovalis. We report the case of a left atrial myxoma originating from the base of the right inferior pulmonary vein. This large myxoma filled a large secundum atrial septal defect, which was diagnosed intraoperatively. The unusual position of this myxoma and operative management of the associated atrial septal defect are discussed. PMID- 8494445 TI - Bronchogenic cyst: a cause of pulmonary artery obstruction and breathlessness. AB - A young woman presenting with breathlessness and a normal chest roentgenogram was found to have unilateral absent lung perfusion on an isotope scan. This was due to a bronchogenic cyst obstructing the right pulmonary artery. This is a rare cause of unilateral absence of lung perfusion and an unusual mode of presentation of a bronchogenic cyst. PMID- 8494446 TI - Blunt cardiac trauma: survival after bichamber rupture. AB - Rupture of cardiac chambers after nonpenetrating blunt thoracic trauma is being recognized with increasing frequency. Despite a high mortality rate, survival after repair of a single-chamber rupture is widely reported. Bichamber cardiac rupture is less frequent, and we report a patient who survived this injury. PMID- 8494447 TI - Identifying Blalock-Taussig shunts using a Silastic band. AB - Placement of an encircling Silastic band around Blalock-Taussig shunts facilitates identification and ligation of the shunt at the time of corrective operation. This technique of "shunt banding" is particularly useful for left sided shunts, both native and modified. We have noted no complications, specifically shunt constriction. Placement of the band adds minimal operative time during shunt placement and substantially lessens the time and amount of dissection required during subsequent procedures. PMID- 8494448 TI - New technique to enlarge the aortic annulus. AB - A new technique is described to enlarge the aortic annulus and the supraaortic area by using the anterior mitral leaflet. This technique is used when it is necessary to replace both the aortic and mitral valves. PMID- 8494449 TI - Augmented femoral venous return. AB - We present a technique of femoral cardiopulmonary bypass that allows excellent venous drainage. This is accomplished by augmenting the venous return with a centrifugal pump. PMID- 8494450 TI - Use of a Dacron cuff to decrease bleeding from atrial cannulas of ventricular assist devices. AB - The use of ventricular assist devices is becoming more common for postcardiotomy cardiogenic shock and as a mechanical bridge to transplantation. Bleeding is the most common complication reported in most clinical series. The sources of bleeding are multiple, but our experience is that a substantial percentage occurred from cannulation sites. We present a technique that we believe decreases the incidence of bleeding from atrial cannulation sites of such devices. PMID- 8494451 TI - Endobag. AB - A simple method for placing specimens in a protective bag during video-assisted thoracic surgery has been developed. The equipment is readily available, and the technique is easy to perform. PMID- 8494452 TI - Aortic subannular ventricular aneurysms. AB - Subannular aneurysms of the left ventricle are rare aneurysms originating adjacent to the aortic or mitral valve. Mitral subannular aneurysms are more common and have been well described. Two cases of aortic subannular aneurysm are reported, and an additional 20 cases were found in the literature. These aneurysms are usually found in young adults who may be seen with congestive heart failure, cardiac murmurs, angina pectoris, myocardial infarction, or even rupture. The aneurysms are often associated with aortic valve anomalies or subaortic stenosis. Diagnosis can be made by echocardiography and cardiac catheterization, and surgical repair is indicated. PMID- 8494453 TI - Motor disorders of the esophagus. PMID- 8494454 TI - Surgical management of carcinoid heart disease. PMID- 8494455 TI - Tumor necrosis factor and platelet-activating factor during cardiopulmonary bypass. PMID- 8494456 TI - Discrete subaortic stenosis. PMID- 8494457 TI - Emergent cardiopulmonary bypass. PMID- 8494458 TI - Ionescu-Shiley bioprosthesis cusp "sag" and insufficiency. PMID- 8494459 TI - Pulmonology and video surgery: color it green. PMID- 8494460 TI - Systematic survey of opinion regarding the thoracic surgery residency. AB - To summarize this rather wide-ranging study, let us review the high points. The future practice of thoracic surgery will be increasingly affected by governmental factors and will have even greater technological dimensions. To do this work, we must continue to attract high-caliber individuals, and this is best accomplished by the early and continuing involvement in the educational process of strong role models from our field. These future surgeons must be motivated to do good work and should have high ethical standards as well as maturity and high intelligence. Experienced, involved faculty leading the residents through a broad program that offers graduated assumption of clinical and leadership responsibilities will facilitate the development of mature clinical judgment. Residents must be taught the clinical skills necessary to do all thoracic operations, leaving subspecialization to postresidency fellowships. The educational program should be humane in its demands and collegial in its application. It should incorporate experiences beyond the operating room, including the opportunity to read, think, and interact with local mentors and colleagues from around the country. The requirements of certification should not be so rigid as to preclude the development of different pathways to the same end. Likewise, although the accreditation process must protect the resident from exploitation, it must not be so restrictive that it does not allow for educational innovation and justifiable differences among programs. These are the thoughtful opinions of our colleagues. They deserve serious consideration. PMID- 8494461 TI - Profile of the contemporary thoracic surgery resident. PMID- 8494462 TI - The practice of medicine in the year 2010. PMID- 8494463 TI - General thoracic surgery in the year 2010. AB - Education and clinical practice in general thoracic surgery will be considerably different in the year 2010. The individual surgeon will most likely see a decline in patient volume and net income. Teaching hospitals with declining profit margins will place monetary constraints on patient programs that do not generate income, and capital budgets will be curtailed. To remain competitive, the general thoracic surgeon will have to keep pace with technologic advances and maintain a current knowledge in the field of thoracic oncology. General thoracic surgical training will profit by a core curriculum with a defined general thoracic surgical faculty dedicated to education in this field. PMID- 8494464 TI - Curriculum change for graduate education in thoracic surgery. PMID- 8494465 TI - Education in thoracic surgery: personal and societal influences. PMID- 8494466 TI - Recruitment and selection of the "best and brightest". PMID- 8494467 TI - Credentialing in medicine. AB - This article describes the history and process of credentialing: accreditation of programs and certification of individual practitioners. Under accreditation, general (institutional) and discipline-specific requirements, both for residencies and fellowships, are considered, along with possible outcomes and the appeals mechanism for an unfavorable review. Under certification, the relationship between individual specialty boards and the American Board of Medical Specialties is defined, followed by a consideration of the principles underlying subspecialty certification and recertification. It is concluded that enforced standards of learning are one of the pillars of accountability upon which a profession must rest; that if medicine abdicates its responsibility to impose credible standards on itself, its place will be taken by very interested, but less knowledgeable, others; and that we must, therefore, rededicate ourselves to the requirement of reasonable standards as a professional obligation and use the best means possible to meet that responsibility. PMID- 8494468 TI - Report of the Joint Conference on Graduate Education in Thoracic Surgery. PMID- 8494469 TI - Variability in resuscitation rates for out-of-hospital cardiac arrest. PMID- 8494470 TI - The consent form revisited. PMID- 8494471 TI - Women, high-density lipoprotein cholesterol, and exercise. AB - Exercise is widely believed to induce favorable changes in the lipid profiles of women, particularly to increase the cardioprotective high-density lipoprotein cholesterol (HDL-C) fraction. A critical appraisal of the literature demonstrates that many research studies fail to consider potential confounders such as hormonal status and body composition. Although cross-sectional studies confirm that active women have higher HDL-C levels than sedentary women, intervention studies suggest that exercise training programs, in the absence of other interventions, do not cause HDL-C levels to rise appreciably in older women. High volumes of exercise may increase HDL-C levels in younger women. Exercise programs of moderate intensity appear to modify the HDL-C-lowering effects of a hypocaloric, fat-restricted diet. PMID- 8494473 TI - Alcohol consumption and risk of ischemic heart disease in women. AB - BACKGROUND: Most studies suggest that alcohol use decreases the risk of coronary heart disease in men, however, this association has not been well established in women. METHOD: This study investigates the relationship between alcohol use and ischemic heart disease (IHD) incidence among women aged 45 to 74 years in the Epidemiologic Follow-up Study of the First National Health and Nutrition Examination Survey. The cohort was free of heart disease at baseline. During the follow-up period (mean, 13 years), 884 IHD cases were identified through hospital records, reported hospital stays, or death certificates. RESULTS: Women reporting any amount of alcohol use had about a 20% decrease in risk of IHD incidence compared with abstainers. Using a Cox regression model to adjust for known cardiovascular risk factors, this relative risk of IHD remained essentially unchanged. The greatest reduction in the risk of IHD (36% to 39%) was among women who consumed about half to two drinks per day compared with abstainers. CONCLUSIONS: This study of a nationally representative sample with a mean follow up of 13 years and a substantial number of IHD cases suggests that moderate alcohol use decreases the risk of IHD. However, the risk and benefits of moderate alcohol consumption need to be viewed within a broader perspective especially since the potentially harmful effects of alcohol have been well documented. PMID- 8494472 TI - Acute pancreatitis. A review with an emphasis on new developments. AB - The spectrum of acute pancreatitis can range from mild and self-limited to severe and fatal. A number of aspects of the condition remain poorly understood or controversial, although recent advances have improved our understanding in many areas. A substantial number of cases of "idiopathic" acute pancreatitis may be caused by occult biliary microlithiasis. The mechanism by which enzymes and bioactive substances become activated within the pancreas is a major unanswered question in acute pancreatitis; however, recent studies suggest that lysosomal enzymes within the pancreatic acinar cell may play a role. A recent refinement in computed tomography, contrast-enhanced dynamic pancreatography, has shown itself to be an extremely useful tool for detecting pancreatic necrosis and its extent, which correlates with the severity of pancreatitis and is useful in identifying patients who may have pancreatic infection and other complications. The management of acute pancreatitis includes supportive measures, observation for development of complications, and the identification of the cause of pancreatitis to prevent recurrences. Specific treatments introduced with the goal of halting the cycle of pancreatic autodigestion and benefiting the course of pancreatitis have generally proved ineffective. Early aggressive treatment of biliary pancreatitis remains controversial; however, endoscopic sphincterotomy may be helpful in more severe cases of biliary pancreatitis if there is no clinical improvement over 48 to 72 hours. Computed tomography-guided percutaneous needle aspiration appears to be a safe and reliable method for diagnosing infected pancreatic necrosis, pancreatic abscess, and infected pancreatic fluid collections. PMID- 8494474 TI - What are representative survival rates for out-of-hospital cardiac arrest? Insights from the New Haven (Conn) experience. AB - BACKGROUND: Survival rates from out-of-hospital cardiac arrests due to ventricular fibrillation or pulseless ventricular tachycardia vary greatly. The majority of published reports indicate a survival range from 11% to 33%, depending on the area of observation. Two recent series from major metropolitan centers describe markedly less favorable outcomes and have led to speculation that dense urbanization may contribute to worse outcomes. METHODS: Examination of a consecutive series of out-of-hospital cardiac arrests in New Haven, Conn, a city of 127,000 people and 55 km2 with a two-tiered emergency response system. All cases of nontraumatic cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia occurring outside of a hospital between January 1988 and June 1989 were considered. That city's emergency medical system employs emergency medical technicians and paramedics. Standard resuscitation techniques were employed; high-dose epinephrine and interposed abdominal counterpulsations were not routine interventions. The main outcome measure was survival to hospital discharge. RESULTS: Three (4.0%) of 75 patients survived cardiac arrest and were discharged alive from the hospital. Two (5.3%) of 38 witnessed arrests resulted in hospital discharges. Patient demographics were typical of those reported from other cities that have published outcomes data. Few patients (16%) received bystander-initiated cardiopulmonary resuscitation. CONCLUSION: There is increasing evidence that previously recognized standards for resuscitation success may not be present in certain types of municipalities, including this northeastern city. A registry of outcomes from out-of-hospital cardiac arrests would help to clarify the true national experience. PMID- 8494475 TI - Adolescent blood pressure in a cohort study of sickle cell disease. AB - BACKGROUND: Previous studies on low blood pressure in patients with homozygous sickle cell (SS) disease have sought new hypotheses on the mechanism of low blood pressure but have not analyzed the role of known determinants such as weight. METHODS: Blood pressure has been measured by an automated oscillometric method in 220 patients with SS disease, 144 with sickle cell-hemoglobin C disease (both groups aged, 9.5 to 18.5 years) and 122 control subjects with a normal hemoglobin genotype (aged 16.0 to 18.5 years) participating in a cohort study from birth. RESULTS: Significant age-related increases in systolic and mean arterial pressure occurred in sickle cell-hemoglobin C disease but not in SS disease. Further analyses were confined to a subgroup of 51 patients with SS, 41 patients with sickle cell-hemoglobin C, and 97 subjects with normal hemoglobin, aged 16.0 to 18.5 years in whom simultaneous measurements of height, weight, arm circumference, and hematologic test results were also available. Crude analyses showed significantly lower systolic, diastolic, and mean arterial pressure in SS disease compared with control subjects with normal hemoglobin, but further analysis showed the systolic difference to be confined to males and all differences disappeared after adjustment for weight. No differences occurred in sickle cell-hemoglobin C disease. CONCLUSIONS: These results suggest that the lower blood pressure in SS disease is attributable to low weight and that no further mechanisms need be postulated. PMID- 8494476 TI - Discussion of preferences for life-sustaining care by persons with AIDS. Predictors of failure in patient-physician communication. AB - OBJECTIVES: To assess the determinants of communication about resuscitation between persons with acquired immunodeficiency syndrome (AIDS) and their physician. DESIGN AND SETTING: Structured patient interview at a staff-model health maintenance organization (HMO), an internal medicine group practice at a private teaching hospital, and an AIDS clinic at a public hospital. PATIENTS: 289 persons with AIDS. MAIN RESULTS: Only 38% of patients had discussed their preferences for resuscitation with their physician. Using logistic regression, we found that patients were less likely to have discussed resuscitation with their physician if they were nonwhite (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24 to 0.99), had never been hospitalized (OR, 0.52; 95% CI, 0.27 to 0.99), or were cared for in the HMO (OR, 0.44 relative to the private teaching hospital; 95% CI, 0.23 to 0.82). Patients were more likely to have discussed their preferences if they were not currently taking zidovudine (OR, 1.76; 95% CI, 1.02 to 3.03) and if they had decided to defer life-sustaining therapy (OR, 2.30; 95% CI, 1.35 to 3.91). Among nonwhites, those with a nonwhite physician were more likely to have discussed resuscitation (OR, 4.38; 95% CI, 1.13 to 16.93). Of patients who had not discussed their preferences for life-sustaining care, 72% wanted to do so. Patient desire for discussion of this issue did not vary by race, severity of illness, hospitalization status, use of zidovudine, or site of care. CONCLUSIONS: A majority of persons with AIDS in this study had not discussed their preferences for life-sustaining care with their physician, despite the desire to do so. Interventions to improve patient-physician communication about resuscitation for nonwhites and other groups at risk of inadequate discussion might lead to clinical decisions that are more consistent with patient preferences. PMID- 8494477 TI - Do not resuscitate orders and the cost of death. AB - BACKGROUND: The appropriate role of cardiopulmonary resuscitation in the hospital continues to be a topic of interest to physicians and patients alike. The use of do not resuscitate (DNR) orders reflects a growing expression of autonomy by patients to refuse medical treatment, and also a growing recognition of its futility in many circumstances by physicians. Although it has been suggested that wider use of advance directives will lead to a reduction in health care costs near the end of life, little empiric data exist to support this prediction. This study was designed to ascertain the rates of DNR orders and their associated costs. METHODS: A retrospective chart review was conducted on the hospital records of 852 of 953 hospital deaths that occurred in a referral hospital. Data were collected on resuscitation status, timing of DNR orders, participants in decision making, and physician and hospital charges. RESULTS: Of the 852 records reviewed, 625 (73%) had a DNR order at the time of death. The use of DNR orders for patients who died ranged from 97% of those on an oncology service to 43% of deaths on cardiology services. One hundred seven patients (17%) had the DNR order before admission. Of 512 patients who had a new DNR order in the hospital, approval was obtained from the patient in only 19%. Patients who died with a DNR order had longer hospital stays (median, 11.0 days) compared with those who died without a DNR order (6.0 days). The time from DNR order to death was 2 days overall with 2.0 days for medical patients and 1.0 day for surgical patients. Average charges for each patient who died were $61,215 with $10,631 for those admitted with a DNR order, and $73,055 for those who had a DNR order made in hospital. CONCLUSION: This study demonstrates high variability in the use of DNR orders between various medical and surgical services. These range from a high of 98% on an oncology service to a low of 43% on cardiology. Most patients have a DNR order at the time of death, but these typically occur late in the course of the hospital stay. Death in the hospital is costly and total hospital and professional charges are significantly lower when a patient is admitted with an established nonresuscitation order compared with those for whom a DNR is established while in the hospital. This study provides a basis against which to measure the impact of efforts such as the Patient Self-Determination Act of 1990 to increase the use of advance directives, as well as monitor their effect on health care expenditures. PMID- 8494478 TI - Ciprofloxacin-induced nephrotoxicity in patients with cancer. AB - Nephrotoxicity associated with ciprofloxacin is uncommon. Five patients with cancer who developed acute renal failure that followed treatment with ciprofloxacin are described and an additional 15 cases reported in the literature are reviewed. Other than elevation of serum creatinine levels, characteristic clinical manifestations and abnormal laboratory findings are not frequently present. Allergic interstitial nephritis is believed to be the underlying pathological-process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. An improvement in renal function that followed the discontinuation of the offending antibiotic supports the presumptive diagnosis of ciprofloxacin-induced acute renal failure. PMID- 8494479 TI - Tuberculosis presenting with generalized lymphadenopathy, pulmonary infiltrates, and bone destruction in a young man. AB - Although tuberculosis is still relatively common in Canada, particularly among recent immigrants, one tends not to consider it very strongly in the absence of definite pulmonary symptoms and in the face of negative smears of expectorated sputum and bronchial washings. We present the case of a young immigrant from Ethiopia who presented with mild constitutional symptoms, bony tenderness of the chest wall, generalized lymphadenopathy, and rib erosions--a set of features which, in the face of smear-negative sputum and bronchial washings, raised a possibility of lymphoma. Eventually, diagnosis of tuberculous lymphadenitis and osteomyelitis was established and the patient responded well to appropriate therapy. PMID- 8494480 TI - Futile resuscitation outcomes. PMID- 8494481 TI - Low serum cholesterol levels and morning suicide. PMID- 8494482 TI - Magnesium effect in electromechanical dissociation (EMD) PMID- 8494483 TI - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XX: 4,4',4''-(1,3,5)-benzene-tris-sydnone imines. AB - The synthesis of ten tris-sydnone imine derivatives, unknown up to now, is described. All compounds are alkyl or arylalkyl substituted in 3-position of the sydnone imine. The most powerful agent was the 3-propyl derivative 6c. It inhibits the aggregation of human platelets induced by collagen in a concentration of 1 mumol/L half maximally. Its N-ethoxycarbonyl derivative 7c, which was designed as a prodrug, showed only small antithrombotic effects in rats. The reason for this low degree of activity is discussed. PMID- 8494484 TI - Studies in hypotensive agents. Synthesis and hypotensive activity of 3,4-dihydro 1(2H)-benzoxepine oxime ethers and their derivatives. AB - Substituted oximino-ethers of 3,4-dihydro-1(2H)-benzoxepines were synthezised from 3,4-dihydro-1(2H)benzoxepin-5-ones. The hypotensive activity of these compounds was evaluated on anaesthetized cats. PMID- 8494485 TI - [Iminium compounds against bacteria and fungi. 29. 3-Alkoxymethyl-1-ethyl-, 3 alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1 butylbenzimidazolium chloride]. AB - Syntheses and antimicrobial activity of 3-alkoxymethyl-1-ethyl-, 3 alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1 butylbenzimidazolium chlorides are described. The compounds were obtained by reaction of 1-ethyl- or 1-butylbenzimidazole with chloromethylalkyl ethers or chloromethylalkyl sulfide. Antibacterial properties were tested on 13 strains of bacteria and fungi. 3-Dodecylthio-methyl-1-ethyl-benzimidazolium chloride exhibited the highest antibacterial activity. PMID- 8494486 TI - Lactones, XXY: Synthesis and 5-HT2-receptor affinity of some fluorophenylated alpha-aminomethyllactones. PMID- 8494487 TI - Homosexual orientation in twins: a report on 61 pairs and three triplet sets. AB - Twin pairs in which at least one twin is homosexual were solicited through announcements in the gay press and personal referrals from 1980 to the present. An 18-page questionnaire on the "sexuality of twins" was filled out by one or both twins. Thirty-eight pairs of monozygotic twins (34 male pairs and 4 female pairs) were found to have a concordance rate of 65.8% for homosexual orientation. Twenty-three pairs of dizygotic twins were found to have a concordance rate of 30.4% for homosexual orientation. In addition, three sets of triplets were obtained. Two sets contained a pair of monozygotic twins concordant for sexual orientation with the third triplet dizygotic and discordant for homosexual orientation. A third triplet set was monozygotic with all three concordant for homosexual orientation. These findings are interpreted as supporting the argument for a biological basis in sexual orientation. PMID- 8494488 TI - Hormones and nocturnal penile tumescence in healthy aging men. AB - There is no information on the relationship between endogenous pituitary and gonadal hormones and nocturnal penile tumescence (NPT) in healthy aging men. Sixty-seven married volunteers ages 45-74 years were studied in the sleep laboratory for 4 nights with the last night devoted to sequential blood sampling every 20 min. Bioavailable testosterone (bT) correlated significantly with several NPT measures while total testosterone, estradiol, LH, and prolactin were mostly unrelated to NPT. All bT-NPT correlations lost their significance after adjustment by multiple regression for the effect of age on both bT and NPT variables in the total subject sample. Analysis of bT-NPT relations by age groups revealed a significant association between bT and duration NPT in men ages 55 to 64 years, but no statistical relations in younger and older age groups. Changes in the central threshold of activation of NPT as age progresses may explain the age-dependent effect of bT in sleep erections. PMID- 8494489 TI - Sexual activities, desire, and satisfaction in males pre- and post-spinal cord injury. AB - Thirty-eight spinal cord injured (SCI) males (median age = 26) completed an 80 item multiple choice questionnaire (median 37 months postinjury) which assessed sexual functioning pre- and post-spinal cord injury in four areas: (i) sexual activities and preferences, (ii) sexual abilities, (iii) sexual desire, arousal, and satisfaction, and, (iv) sexual adjustment. Frequency of sexual activity decreased following SCI with a reduction in intercourse and increased interest in alternative sexual activities. Of complete quadriplegic subjects 38% reported the ability to have an orgasm accompanied by ejaculation underscoring the need for physiological studies. Partner's desire for sex as perceived by the SCI individual was correlated with frequency of sex and numbers of sexual partners postinjury. Subject's perceptions of their own and partner's sexual desire decreased following SCI. Sexual satisfaction decreased postinjury and was positively correlated with both the patients' and their partners' interest in penile-vaginal intercourse. Of the subjects, 27% reported sexual adjustment difficulties and 74% relationship difficulties but only 22% received counseling. Results indicate the importance of the availability and desire of a sexual partner in the sexual activities and satisfaction of the SCI individual. SCI patient and staff sexual education and counseling continue to be strong needs. PMID- 8494490 TI - Social/sexual awareness of persons with autism: a parental perspective. AB - A parental survey that addressed the social sexual awareness, sex education, and sex behaviors of persons with autism, a developmental disability is provided. Questionnaires from 100 caregivers of persons with autism 9 years of age and older and with the DSM-III-R diagnosis were analyzed. Eighty-five percent of respondents were mothers, 8% both parents, 5% fathers, and 2% others; 32% of the persons with autism were female and 68% male with an age range of 9.1 to 38.9 years. The verbal level of the person with autism related to parents' beliefs about the relevance of sex relations (chi 2 = 6.99, p < 0.05) and sex education (chi 2 = 22.91, p < 0.001). No relationship between parents' report of the verbal level of the individual and the display of inappropriate sexual behaviors was found (chi 2 = 2.56, ns). Parents of males were more concerned about their son being taken advantage of by a same-sex person (chi 2 = 15.90, p < 0.001); parents of females were worried about an opposite-sex person (chi 2 = 4.06, p < 0.05). Parental concerns and beliefs regarding sexuality varied and could not be generalized. The nonsignificant finding regarding verbal level and display of inappropriate sexual behaviors suggests that the need for sex education is best determined by the behaviors of the person rather than the functioning or verbal levels. PMID- 8494491 TI - Varieties of autogynephilia and their relationship to gender dysphoria. AB - The relationship between gender dysphoria and autogynephilia (erotic arousal in men associated with the thought or image of themselves as women) was investigated. Subjects were 238 nonhomosexual male outpatients divided into three groups: 94 reporting they were most aroused sexually by images of themselves as nude women, 67 most aroused by images of themselves as women in underwear, and 77 most aroused by images of themselves as fully clothed women. These were compared on questionnaire measures of gender dysphoria and other psychosexual variables. The Nude group was significantly more gender dysphoric than the Clothed group, which, in turn, was significantly more gender dysphoric than the Underwear group. These results support the hypothesis that those nonhomosexual men most aroused sexually by the thought of having a woman's body are also those most interested in acquiring a woman's body through some permanent, physical transformation. A secondary finding was that the Nude group was the same age as the Underwear group and significantly younger than the Clothed group. This outcome makes it unlikely that erotic fantasies of having a woman's body are the end result of some progression that necessarily begins with erotic fantasies of wearing women's clothes. PMID- 8494492 TI - Person drawings by transsexual clients, psychiatric clients, and nonclients compared: indicators of sex-typing and pathology. AB - The drawings by 31 transsexual clients, 61 psychiatric inpatients, and 62 nonclient college students were compared to derive information about whether they differed with regard to sex-typing and psychopathology. Transsexuals did not differ from nonclients or psychiatric patients as far as their conceptualization of masculinity is concerned, nor are they more or less sex-role stereotyped. However, their conceptualization of femininity of women differs significantly from that of the other groups in that transsexuals view women as more feminine than either of the other groups. Finally, transsexuals differed from both nonclients and psychiatric patients in inconsistent patterns across other variables, indicating that they are neither similar to nonpathological controls, nor to psychiatric inpatients. This uniqueness of the transsexual group is discussed in the context of multiple possible interpretations. PMID- 8494493 TI - Sexual aggression and love styles: an exploratory study. AB - The relationship between sexual aggression and theoretical love styles was studied. Based on self-reported sexual history, 63 college men were grouped as having either consensual sexual experience only (n = 33) or having verbally coercive sexual experience (n = 30). Analyses were conducted using six love style scales, likelihood to rape, likelihood to use sexual force, masculinity, and sociopathy to predict sexual coercive group membership. Logistic regression indicated that the Ludus love style, a manipulative, game-playing orientation towards intimate relationships, was the best predictor of sexual coercion among the six love styles. Additionally, logistic regression indicated that the Ludus love style was as effective in classifying men as coercive or noncoercive as other dispositions related to sexual aggression. These results suggest that the Ludus love style may serve as a unifying construct for dispositions related to sexual aggression. This study constitutes an initial attempt to link sexually coercive behaviors to a theoretical model of intimate relationships. Results are discussed in the context of a situational model of sexual coercion. PMID- 8494494 TI - A physiologically based pharmacokinetic model for butadiene and its metabolite butadiene monoxide in rat and mouse and its significance for risk extrapolation. AB - The gas 1,3-butadiene (BU) is an important industrial chemical and an environmental air pollutant. BU has been shown to be a weak carcinogen in the rat but a potent carcinogen in the B6C3F1 mouse. This species difference makes risk extrapolation to humans difficult and the underlying mechanism should be clarified before meaningful risk extrapolation to humans can be made. One possible explanation for the species differences in cancer response is that there are quantitative species differences in the formation of genotoxic epoxides. To investigate this possibility a physiologically based pharmacokinetic (pbpk) model for BU together with its first reactive metabolite 1,2-epoxybutene-3 (butadiene monoxide, BMO) was developed. Previously reported values on hepatic glutathione (GSH) turnover, depletion of hepatic GSH in rodents exposed to BU, and in vitro metabolic data of BU and BMO were included in the model, which incorporates intrahepatic first-pass hydrolysis of BMO and the ordered sequential, ping-pong mechanism to describe the enzyme kinetics of BMO-GSH conjugation. In vitro studies were carried out to obtain tissue: air partition coefficients of BU and BMO in rat tissue homogenates. The simulated pharmacokinetics of BU, BMO, and GSH agreed with previously published experimental observations in rat and mouse obtained in closed and open chamber experiments. According to the model, the internal dose of BMO (expressed either as the concentration in mixed venous blood or as the area under the concentration-time curve) is approximately 1.6 times higher in the mouse than in the rat for exposure to BU below 1000 ppm. At higher exposure levels, GSH depletion occurs in the mouse, but not in the rat, after about 6-9 h. This GSH depletion results in up to 2-3 times higher internal doses in the mouse than in the rat. The clear but relatively small species differences in body burdens of BMO indicated from our model can only partly explain the marked species difference in cancer response between mice and rats exposed to BU. PMID- 8494496 TI - Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. AB - A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population ("conjugators") possess, whereas one quarter ("non-conjugators") lack this specific activity. A standard method for the identification of conjugators and non-conjugators with the use of methyl bromide and gas chromatography (head space technique) is described. Three substrates of the polymorphic enzyme, methyl bromide, ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. All three substances led to a marked increase of sister chromatid exchanges (SCE) in the lymphocytes of the non-conjugators but not in those of conjugators. A protective effect of the glutathione-S-transferase activity in human erythrocytes for the cytogenetic toxicity of these chemicals in vitro is thus confirmed. Since the enzyme activity is not found in erythrocytes of laboratory animals, species extrapolations for risk assessment of methyl bromide, ethylene oxide and dichloromethane should be reconsidered. PMID- 8494495 TI - Modulation of acrylonitrile-induced embryotoxicity in vitro by glutathione depletion. AB - The effects of glutathione (GSH) depletion on the embryotoxicity of acrylonitrile were assessed in vitro using the rat whole-embryo culture system. Day 10 rat embryos were cultured in rat serum medium for 6 h in the presence of 250 microM L buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH synthesis, to deplete GSH in both embryo and visceral yolk sac. Following pretreatment, conceptuses were cultured for an additional 21 h in the presence of 152, 228, or 304 microM acrylonitrile. At the end of the culture period, conceptuses were assessed for survival, growth and development, malformations, and the protein and glutathione content of embryos and yolk sacs were assayed. Acrylonitrile alone produced concentration-related and statistically significant decreases in yolk sac diameter, crown-rump length, head length and number of somite pairs, as well as in embryonic and yolk sac proteins. The chemical also caused dysmorphogenesis of the brain and of the caudal extremity, and a concentration-related and statistically significant increase in GSH content in the yolk sac. Pretreatment with BSO significantly enhanced the embryotoxic effects of acrylonitrile. The conceptuses displayed further decreases in functional yolk sac circulation, yolk sac diameter, crown-rump and head length, when compared to either acrylonitrile or BSO alone. The incidence of caudal malformations and the severity of brain malformations produced by acrylonitrile were also increased. Marked decreases in embryonic and yolk sac GSH contents were observed after exposure to BSO alone or in combination with acrylonitrile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494497 TI - Formation of N-methyl protoporphyrin in chemically-induced protoporphyria. Studies with a novel porphyrogenic agent. AB - 1-[4-(3-Acetyl-2,4,6-trimethylphenyl)-2,6-cyclohexanedionyl]-O-eth yl propionaldehyde oxime (for short ATMP) is a novel porphyrogenic agent causing hepatic protoporphyria in the mouse. Mice given a single dose of the drug showed 24 h later a 70% inhibition of liver ferrochelatase and marked accumulation of protoporphyrin. These changes were not seen in similarly treated rats, guinea pigs, hamsters or chick embryos. A green pigment was isolated from the liver of mice treated with ATMP and identified by its electronic absorption spectrum and chromatographic properties on HPLC as N-methyl protoporphyrin. The ATMP pigment markedly inhibited the enzyme ferrochelatase in vitro, thus supporting its identification as N-methyl protoporphyrin. Two inhibitors of liver cytochrome P450, compound SKF 525-A and piperonyl butoxide, when given before ATMP, afforded protection against ATMP-induced porphyria and production of N-methyl protoporphyrin, suggesting a role of cytochrome P450 in the induction of the metabolic disorder. The most likely interpretation for these findings is therefore that ATMP is metabolized in the mouse to a reactive species, which in turn alkylates the haem moiety of liver cytochrome P450, thus producing N-methyl protoporphyrin. This inhibits ferrochelatase and, as a secondary response, protoporphyrin accumulates. This pathway of metabolism to the postulated reactive metabolite presumably does not occur to a significant extent in the other species examined and hence is the likely basis for the species difference in protoporphyria. PMID- 8494498 TI - The cortical epithelium of the rat thymus after in vivo exposure to bis(tri-n butyltin)oxide (TBTO). An (immuno)histological and ultrastructural study. AB - Bis(tri-n-butyltin)oxide (TBTO) induces cortical atrophy in the rat thymus. We studied the potential involvement of the cortical epithelium in TBTO-induced thymotoxicity by (immuno) histology and electron microscopy. Juvenile male Wistar rats were orally intubated once with either 30 or 90 mg/kg TBTO and sacrificed 4 or 10 days later. A dose-dependent thymic atrophy occurred. Anti-keratin labelling showed epithelial cell aggregation in some animals at 10 days after exposure to 90 mg/kg TBTO, when recovery of the thymus was apparent. At the ultrastructural level, a relative shift was observed from "pale" to darker epithelial cell subtypes at the 30 mg/kg dose level, both at day 4 and day 10 after intubation. This phenomenon was not observed after exposure to 90 mg/kg TBTO. Both the altered keratin distribution and the increased electron density of the epithelium probably represent non-specific phenomena. The present morphological observations support the concept that TBTO affects the thymus via its action on lymphoid cells rather than on the epithelial compartment. PMID- 8494500 TI - Lipid abnormalities in rats given small doses of lead. AB - Previous human and experimental studies have demonstrated that lead exposure may modify the metabolism of lipids. Several studies have indicated that exposure to lead produces an increase in lipid peroxidation and inhibits blood superoxide dismutase activity. Recently, lipid peroxides have been shown to impair tissue membranes and to be a risk factor for vascular diseases. The aim of the present investigation was to evaluate the impact of subclinical lead poisoning on rat lipids in the context of atherosclerosis. The degree of poisoning was analogous to that in populations exposed to lead in a contaminated environment. Experiments were performed on male Buffalo rats with body weights of 150-200 g. The experimental animals received lead acetate intragastrically in doses of 35 mg lead/kg body wt. (Pb/kg) once weekly or 70 mg Pb/kg twice weekly for 7 weeks. Control rats were fed in the same manner with sodium acetate equimolar to the acetate in the lead acetate solution. One day after the feeding was over, venous blood samples, under ether anesthesia, were collected. The animals were killed by exsanguination and the liver was excised for determination of the metal (lead, copper, and zinc) content. A segment of the abdominal aorta was excised for histological examination. In venous blood the following were estimated: triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol fraction, serum lipid peroxides, and blood superoxide dismutase activity. Metal content (lead, copper, and zinc) in blood and liver was determined by means of atomic absorption spectrophotometry. In rats poisoned with small doses of lead, decreases in the plasma cholesterol level and the HDL-cholesterol fraction were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494499 TI - Electroencephalographic and autonomic responses to trichloroethylene inhalation in freely moving rats. AB - Effects of trichloroethylene (TRI) on the central nervous system (CNS) and autonomic functions were examined by means of continuous polygraphic measurements of electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG) in electrode-implanted and freely moving rats, while they were exposed via inhalation to TRI vapor of 300, 1000 or 3000 ppm for 8 h/day or 6000 ppm for 4 h/day on 3 consecutive days. The exposures to 3000 and 6000 ppm produced abnormal EEG activity and incapacitation of postural maintenance during the exposure period, while the post-exposure period was characterized by decreased waking (W) time, lowered heart rate (HR) and increased numbers of bradyarrhythmic episodes after recovery from anesthesia. The exposure to 1000 ppm decreased W time without the appearance of anesthesia. The exposure to 300 ppm did not produce any observable effects except the lowered HR, which occurred during the post-exposure period. The relationships between internal doses of TRI and its metabolites and these TRI-induced pathophysiological responses were determined by blood and brain analyses of TRI, trichloroethanol and trichloroacetic acid in the TRI-exposed rats. Recordings of respiratory chest wall movement revealed that the number of TRI-induced bradyarrythmias accompanying apnea during paradoxical sleep (PS) increased significantly after cessation of exposure to 6000 ppm TRI. This suggests that TRI-induced hypoxemia due to apnea during PS triggers bradyarrhythmogenesis through increased cardiac vagal efferent tone. PMID- 8494501 TI - Effect of pyridostigmine pretreatment, HI-6 and Toxogonin treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure. AB - The ex vivo contraction response of the rat tracheal smooth muscle was examined after 10 min in vivo inhalation of soman and/or pretreatment with pyridostigmine and/or post-exposure treatment with HI-6 ([[[(4 aminocarbonyl)pyridinio]methoxy]methyl]-2[(hydroxy imino) methyl]pyridinium dichloride) or Toxogonin (1,1'-[oxybis-(methylene)]bis[4-[(hydroxyimino)methyl] py rid inium] dichloride). In vivo pretreatment with pyridostigmine was achieved by subcutaneous (s.c.) implantation of an osmotic pump that delivered pyridostigmine continuously (0.01 mg/h) in the neck region of the rat 18 h before soman exposure. The ex vivo cholinergic tracheal smooth muscle response increased during the first 60 min after soman exposure in animals pretreated with pyridostigmine. The amplitude of the contraction response in pyridostigmine pretreated animals was about 60% of control, compared to 15% of control without pyridostigmine pretreatment. Pyridostigmine pretreatment also produced significant recovery of the total cholinesterase (ChE) activity in plasma, but not in trachea and lung. Intraperitoneal (i.p.) injection of HI-6 or Toxogonin (50 mg/kg), immediately after 10 min inhalation exposure to soman, also significantly improved the ex vivo cholinergic contraction response of the trachea (decapitation 15 min after oxime administration). The recovery of the physiological response with Toxogonin was, however, not stable. HI-6 was superior to Toxogonin with respect to the initial airway contraction response, and the response increased up to a stable level not significantly different from control. There was no significant reactivation of the ChE activity after treatment with the oximes. Combination of pyridostigmine pretreatment and oxime treatment enhanced the recovery of the tracheal contraction response and the ChE activity in the trachea compared to treatment with oximes alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494502 TI - A homogeneous immunological detection system for soman using the in vitro protection of acetylcholinesterase by a monoclonal antibody. AB - In this study a monoclonal antibody (MAb) based soman detection system was investigated. Since the MAb F71D7 recognizes the pinacolyl group of soman, non toxic soman analogues are also detected when using an indirect competitive ELISA. This can lead to falsely positive results. The toxic effect of soman is, however, independent of the pinacolyl group. In the described homogeneous enzyme immunoassay (EIA), the inhibitory effect of soman on acetylcholinesterase (AChE) was combined with its specific binding to the MAb F71D7 in order to minimize false positive results and enhance the specificity of the detection system. In this rapid EIA no incubation or washing steps are necessary, so only time for pipetting and reaction have to be considered. Soman could be detected in concentrations of 1.6-25 nM using the EIA. This corresponds to 8 pg soman per 25 microliters sample and means that compared to other ELISA systems, besides enhanced specificity, the limit of detection could be improved by 3 orders of magnitude. PMID- 8494503 TI - Trichloroethylene exposure in vapour degreasing and the urinary excretion of N acetyl-beta-D-glucosaminidase. AB - In order to elucidate the potential nephrotoxicity of low level occupational exposure to trichloroethylene (TRI), urine analysis of the tubular enzyme N acetyl-beta-D-glucosaminidase (U-NAG) was included in a cross-sectional study of metal degreasers in central Sweden. Eighty-six percent of 8-h TRI in air measurements were well below 50 mg/m3. Normal levels of NAG were found in morning urine samples from 29 workers compared to a historical reference group. A weak positive correlation (r = 0.48; P < 0.01) was observed between U-NAG activity and the concentration of the TRI metabolite trichloroacetic acid in urine but not with other estimates of recent or long-term exposure. In conclusion, TRI does not seem to be nephrotoxic at low exposure levels. PMID- 8494504 TI - Marginal seal of cervical tooth-coloured restorations. A laboratory investigation of placement techniques. AB - Incremental placement of composite resin has been suggested as a means of overcoming the contraction that occurs during polymerization of the composite material and as a consequence should allow an improved gingival dentine seal. Numerous incremental placement techniques for composite resin restorations have been documented in the literature. This study examined four different methods of placing Silux in class V cavities, located in the region of the cemento-enamel junction, and lined with Vitrabond. None of the placement methods used completely sealed either the enamel or dentine margins. Of the four techniques employed, the one which involved incremental placement of the gingival component first showed the least amount of leakage at the dentine margin. This result, however, was only significantly different from that of the bulk placement method. In the majority of cases where leakage did occur at the dentine margin, it progressed no further than the Vitrabond lining. It appeared that the high initial adherence to dentine of the light cured glass-ionomer cement prevented deeper penetration of the dye. PMID- 8494505 TI - The importance of oral foci of infection in renal transplantation. AB - During the treatment of patients with renal failure or renal transplants the most important consideration is to eliminate sources of infection before and after the treatment. Acute or chronic oral infections or bacteraemias resulting from dental procedures may cause serious complications in these patients who already have lowered host resistance caused by immunosuppressant therapy. In order to determine the latest concepts from some international transplantation centres relating to the importance of and the effect of infective sources in the oral cavity, a survey form was prepared which included several questions related to oral foci of infection and renal transplantations. Results obtained from 22 centres from 12 countries indicated that the majority of the centres included a dental examination in their routine protocol and required completion of any necessary dental treatment before transplantation. However, full agreement among all these centres on the necessity for dental examination as part of the protocol has not yet been reached. PMID- 8494506 TI - Xerostomia: the missing diagnosis? AB - Xerostomia is a distressing condition which may be associated with a number of specific diseases, iatrogenically induced following the administration of drugs or radiotherapy, or the result of inflammatory processes affecting salivary gland tissue. In this article epidemiological background is briefly reviewed and aetiological conditions associated with xerostomic states are summarized. The oral sequelae of xerostomia are discussed and approaches to diagnosis demonstrated. Treatment of xerostomia is basically supportive and the main elements are presented. PMID- 8494507 TI - Mandibular central giant cell granuloma associated with sclerosing osteomyelitis of Garre (periostitis ossificans). Case report. AB - Garre's sclerosing osteomyelitis or periostitis ossificans with a radiographic 'onion skin' appearance is a separate clinical entity. The new bone formation underneath the periosteum is a response of periosteum to stimulation by low grade infection. This may occur in a variety of other developmental, metabolic, inflammatory and neoplastic diseases of bone. A case of mandibular giant cell granuloma of a central type associated with Garre's sclerosing osteomyelitis is presented and the literature is reviewed. PMID- 8494508 TI - Pre-operative diflunisal for pain relief following third molar surgery under general anaesthesia. AB - In order to find out whether long-acting non-narcotic analgesics given pre operatively reduce the post-operative pain and decrease the narcotic analgesic requirements following third molar surgery under general anaesthesia, thirty Hong Kong Chinese patients undergoing this procedure were randomly given either diflunisal or placebo one hour prior to anaesthesia. Pain reduction was monitored for ten hours from the end of surgery using visual analogue scales. Except in the first hour, pain reduction at each hour was significantly better in the diflunisal group than in the placebo group. Furthermore, only one patient required narcotic analgesics in the diflunisal group compared with five in the placebo group. In patients who had multiple tooth sectioning or very difficult surgery of one or both lower third molars, the requirement for post-operative analgesics was high in the placebo group. PMID- 8494509 TI - The development of the dental high-speed air turbine handpiece. Part 2. PMID- 8494510 TI - A proposal for voluntary continuing dental education accreditation. AB - The paper proposes a simple method of voluntary continuing dental education accreditation for dentists. It is suggested that the Australian Dental Association should adopt a positive role in promoting a method of accreditation for its members. The reasons for such a scheme are discussed in the light of the current scrutiny directed at the professions on this important issue. PMID- 8494511 TI - A buried deciduous molar. Case report. PMID- 8494513 TI - Can dentists keep their professionalism? PMID- 8494512 TI - Clinical Note No. 12. Local anaesthesia for 'hot pulp' mandibular molars. PMID- 8494514 TI - Defence case known as 'heart'. PMID- 8494515 TI - Prophylaxis for the prevention of infective endocarditis. PMID- 8494516 TI - Endocarditis prophylaxis. PMID- 8494517 TI - A retrospective clinical evaluation of resin-bonded bridges inserted at the Adelaide Dental Hospital. AB - The clinical performance of resin-bonded Rochette and Maryland bridges inserted by various operators at the Adelaide Dental Hospital is reported. Thirty-four Rochette bridges (30 anterior, 4 posterior) and 228 Maryland bridges (150 anterior, 78 posterior) were assessed. Clinical data were compiled on types of bridge failure, factors influencing bridge retention, and the effects of the prostheses on abutment teeth and supporting tissues. The failure rate for Rochette bridges over 6 years was 75 per cent with a median survival of 2.14 years. Debonding occurred in 70 per cent of bridge failures. The failure rate for Maryland bridges over 5 years was 42 per cent with a median survival of 2.60 years. Pontic fracture (29 per cent) and debonding (20 per cent) were the main failures observed. Porcelain pontics performed significantly better than the processed hybrid resin pontics (P < 0.01). The main reasons for debonding included occlusal stresses, non-retentive bridge designs and resin cement failure. A life-table analysis showed no significant difference in the overall cumulative survival rates between Rochette and Maryland bridges. Bridge design and the choice of pontic material and resin cement emerged as significant factors influencing the success rate of the bridges examined. PMID- 8494518 TI - Deformation of vented crowns with fluids of differing viscosities. AB - Venting of full crown restorations is an effective aid to seating during cementation. Vent hole repair complicates placement procedures and potentially disturbs the coronal integrity of the restoration. Cervical deformation of crowns during cementation was measured with circumferential strain gauges. Crowns were able to be vented occlusally, and two silicone fluids of widely differing viscosities were used. Venting significantly decreased the time to seat for both viscosities. It also decreased deformation of crowns cemented with low viscosity fluid, but increased deformation during cementation with high viscosity fluid. The values of deformation were nearing clinical significance for ceramic systems. Increased axial wall separation gave a similar decrease in seating times, but with no increase in deformation. The advisability of venting is questioned when high viscosity cements are used, and methods of increasing axial wall separation are recommended. PMID- 8494519 TI - Circoviridae: new viruses of pigs, parrots and chickens. PMID- 8494520 TI - Maturation of insulin and glucose responses to normal feeding in foals. AB - Postprandial insulin and glucose concentrations were measured in 3 Arabian and 3 Thoroughbred foals at 1 day, 1 week, 1 month and 3 months of age. Prefeeding serum insulin concentrations were similar in foals at 1 day (25.9 +/- 5.1 pmol/L), 1 week (32.4 +/- 5.8 pmol/L), and 1 month (38.2 +/- 7.9 pmol/L), but had increased significantly to 131.0 +/- 20.2 pmol/L at 3 months of age (P < 0.05). There was significantly increased serum insulin secretion after a feed in foals at 3 months of age (P < 0.05) when compared with that at younger ages. Prefeeding serum glucose concentrations ranged from 6.0 +/- 0.7 mmol/L at 1 day, to 5.9 +/- 0.9 mmol/L at 1 week, 4.9 +/- 1.7 mmol/L at 1 month, and 4.4 +/- 1.5 mmol/L at 3 months of age. There were lower postprandial glucose concentrations with advancing age. It appeared that there was a period of maturation in pancreatic beta-cell function after birth in foals, which reached adult levels by 3 months of age. PMID- 8494521 TI - Laboratory diagnosis of psittacine beak and feather disease by haemagglutination and haemagglutination inhibition. AB - Simple and sensitive haemagglutination and haemagglutination inhibition assays were developed for psittacine beak and feather disease (PBFD) virus and serum antibody, respectively. The assays were used in the examination of samples from 73 birds clinically affected with PBFD. High antigen titres (log2 9 to log2 12) were detected in feathers, faeces and cloacal contents of PBFD-affected birds. Antigen was not detected in either faecal or feather samples from 20 normal galahs (Eolophus roseicapillus) and 9 normal sulphur crested cockatoos (Cacatua galerita). After kaolin treatment and haemadsorption of serum, haemagglutination inhibition (HI) antibody titres could not be detected in serum from 42 PBFD affected birds, whereas serum HI titres from 64 normal psittacine birds ranged from less than log2 1 to log2 8. Serum and yolk HI antibody responses of 6 PBFD virus-inoculated layer hens were measured. Pre-inoculation chicken sera contained high concentrations of non-specific haemagglutination inhibitors (not detected in chloroform-extracted yolk), which were removed by kaolin treatment and haemadsorption. PMID- 8494522 TI - Seroprevalence of psittacine beak and feather disease in wild psittacine birds in New South Wales. AB - A haemagglutination inhibition assay was used to detect antibody to psittacine beak and feather disease virus in sera from wild sulphur crested cockatoos (Cacatua galerita), galahs (Eolophus roseicapillus), short-billed corellas (Cacatua sanguinea), eastern long-billed corellas (Cacatua tenuirostris) and other psittacine birds in New South Wales. The seroprevalence of psittacine beak and feather disease ranged from 41% to 94% in different flocks, indicating infection with the virus is widespread in wild populations. PMID- 8494523 TI - Vetch toxicosis in cattle grazing Vicia villosa ssp dasycarpa and V benghalensis. AB - The epidemiological, clinical and pathological features of a disease syndrome in adult cattle grazing woolly-pod vetch (Vicia villosa ssp dasycarpa) or popany vetch (V benghalensis) are reported. Outbreaks of toxicosis occurred between midwinter and midsummer in 3 dairy and 6 beef herds on the north coast of New South Wales, between 1982 and 1992. Friesian, Angus, Murray Grey, Guernsey and Hereford breeds were affected. Mean morbidity and case fatality rates in affected herds were 7% (65 of 889) and 69%, respectively. Signs of pruritic dermatitis, illthrift and death were associated with an eosinophilic granulomatous inflammation of many organs, particularly involving the renal cortex, dermis, myocardium, adrenal glands, lymph nodes and hepatic portal triads. PMID- 8494524 TI - Development of government veterinary services in South Australia 1840-1970. PMID- 8494525 TI - Persistence of the sheep body louse, Bovicola ovis, after treatment. AB - Lice were found in samples of baled wool from 198 of 464 flocks treated to eliminate an infestation in the period July 1988 to June 1990. In 287 flocks the insecticide was applied as a backline treatment and in 177 flocks a shower dip was used. Of these flocks, 41.5% and 44.6%, respectively, were found to be infested at the following shearing. After adjusting for the accuracy of the test, it was estimated that infestation in 2 consecutive 12-month periods occurred in 52.6% of flocks with a real incidence rate of 27.4%. Using these estimates, it was calculated that in 34.7% of infested flocks treatment did not kill all lice. There were no differences in the proportion of consecutive infestations between flocks treated with any of the 3 chemicals applied as backline treatments. Among flocks treated in a shower dip, 68.4% using coumaphos, 37.8% using diazinon and 41.5% using cyhalothrin had consecutive infestations (P < 0.05). The detection of lice in 63.2% of flocks that were treated with magnesium fluosilicate was, in part, attributed to the application of this chemical by one operator. PMID- 8494526 TI - A one-way (non-rebreathing) valve suitable for use in gas analysis of exercising horses. PMID- 8494527 TI - Sarcocystis spp in Western Australian sheep. PMID- 8494528 TI - A comparison of serum immunoglobulin concentrations in neo-natal calves fed substitute colostrums. PMID- 8494529 TI - Cervicothoracic vertebral subluxation causing ataxia in sheep. PMID- 8494530 TI - Anomalous antidiuretic activity of antidiuretic hormone antagonists. PMID- 8494531 TI - Stereoselective microsomal N-oxidation of N-ethyl-N-methylaniline. AB - The stereoselectivity of metabolic N-oxidation of N-ethyl-N-methylaniline (EMA) was investigated in vitro following incubation of the compound (1mM) with fortified hepatic microsomal preparations of both male Wistar rats and New Zealand White (NZW) rabbits. The major metabolites in both species were found to be N-ethylaniline, N-methylaniline and EMA N-oxide. Chromatographic resolution of the N-oxide enantiomers was achieved using a Chiralcel OD stationary-phase with a mobile-phase of hexane:ethanol (98:2, v/v). Examination of the enantiomeric composition of the N-oxide metabolites indicated a predominance of the (-)-(S)-N oxide from both species with enantiomeric excesses of 52 +/- 2.5% and 65 +/- 2.1% (n = 3) in rat and rabbit tissue respectively. These preliminary observations indicate that the N-oxidation of EMA shows product stereoselectivity, the extent of which varies between species. PMID- 8494532 TI - Agonist-stimulated Cl- efflux from human neutrophils. A common phenomenon during neutrophil activation. AB - When human peripheral blood neutrophils were stimulated with various agonists which activate and/or prime neutrophils, we found that Cl- efflux was enhanced with a dramatic (50%) loss of intracellular Cl-. Interestingly, the Cl- efflux was enhanced by both agonists which induce a rapid transient increase in intracellular Ca2+ concentration ([Ca2+]i) [class I, e.g. N-formyl-methionyl leucyl-phenylalanine (fMLP), interleukin-8 (IL8), platelet-activating factor, leukotriene B4 and C5a] and those which do not induce such an [Ca2+]i elevation [class II, e.g. tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. The time course of agonist-stimulated Cl- efflux differed depending on the agonist. Class I agonists such as IL8 and fMLP exhibited a 1 min lag phase before the onset of Cl- efflux; class II agonists such as GM-CSF and TNF displayed a 2 and 5 min lag phase, respectively. Both IL8 (class I)- and TNF (class II)-stimulated Cl- efflux exhibited similar sensitivity to inhibition by different types of ion transport inhibitors [ethacrynic acid (EA), amiloride, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, anthracene-9-carboxylic acid, and 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid]. On the other hand, natural Cl- efflux, which is thought to be mainly mediated by Cl-/Cl- self exchange, was not inhibited by EA (0.5 mM) or amiloride (0.3 mM). These results imply that both class I and class II agonist-stimulated Cl- efflux occurs via a common Cl- transporter which is different from that reported previously in resting human neutrophils. Although all agonists which induced a Cl- efflux also induced shape change of neutrophils, there did not appear to be a causal relationship between shape change and agonist-stimulated Cl efflux. However, a temporal correlation was found to exist between agonist stimulated Cl- efflux and intracellular alkalinization following agonist stimulation. Agonist-stimulated Cl- efflux therefore seems to be a common phenomenon activated by several agonists which act through different signal transduction pathways. PMID- 8494533 TI - Cytostatic and cytotoxic properties of the marine product bistratene A and analysis of the role of protein kinase C in its mode of action. AB - Bistratene A is a polyether which was isolated from the marine ascidian Lissoclinum bistratum Sluiter. The hypothesis has been tested that the cytostatic effect of bistratene A is mediated by modulation of protein kinase C (PKC). Human derived A549 lung and MCF-7 breast adenocarcinoma cells are extremely sensitive to growth inhibition induced by activators of PKC. Therefore, the effect of bistratene A on these cell lines was compared with that of the known PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA). The ability of bistratene A to modulate PKC activity in cellular cytosol was assessed to determine the involvement of PKC in the induction of cytostasis. Bistratene A inhibited the growth of both cell lines and initial seeding density determined its cytostatic potency. IC50 values were between 1.0 and 2.9 nM. Bistratene A also had a profound effect on the colony forming ability of A549 cells, preventing clonal growth at 5 nM. Using the incorporation of [3H]thymidine into cells to assess DNA synthetic activity and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to define cytotoxicity, the compound was found to have both cytostatic and cytotoxic properties. Bistratene A decomposed by 50% after only 2.8 hr in cell culture medium. TPA induced rapid motility and the formation of a network of branched colonies in both cell lines grown on Matrigel, whereas bistratene A did not cause the same effect. Cell cytosol was analysed for phorbol ester binding sites after treatment with bistratene A or TPA. Incubation with TPA (10 nM) caused a reduction in binding sites to 57% of binding in control cells after 30 min and to 35% after 24 hr. Bistratene A did not cause a significant change in binding sites. Assays of PKC activity in cellular cytosol revealed that bistratene A was unable to activate or inhibit the enzyme at concentrations of up to 10 microM. The results suggest that bistratene A is an exquisitely potent cytostatic agent in the two cell lines studied, but modulation of PKC is not involved in the mode of action by which it elicits this effect. PMID- 8494534 TI - Transport of bestatin in rat renal brush-border membrane vesicles. AB - Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine] is a dipeptide, comprising L-leucine and an unusual beta-amino acid. We studied its transport mechanism in rat renal brush-border membrane vesicles. Uptake of cephradine, an aminocephalosporin, by isolated brush-border membrane vesicles was trans stimulated and cis-inhibited by bestatin, indicating that these drugs are transported via the same transport system(s). The uptake of bestatin was trans stimulated by preloading the vesicles with glycylsarcosine, and was cis-inhibited by substrates for the H+/dipeptide cotransport system. Bestatin inhibited tetraethylammonium (an organic cation) uptake, and bestatin uptake was cis inhibited by substrates for the H+/organic cation antiport system. In addition, bestatin uptake was stimulated by an outward H+ gradient (the driving force for the H+/organic cation antiport system). These findings suggest that bestatin, in spite of being a dipeptide, is transported via not only the H+/dipeptide cotransport system but also the H+/organic cation antiport system in rat renal brush-border membrane. PMID- 8494535 TI - Elevation of cysteine and replenishment of glutathione in rat lung slices by cysteine isopropylester and other cysteine precursors. AB - In this study, we have used a rat lung slice model to compare the ability to several potential cysteine delivery systems (L-cysteine isopropylester, L cysteine cyclohexylester, N-acetylcysteine, L,2-oxo-4-thiazolidine carboxylic acid and cysteine) to elevate cysteine and glutathione (GSH) levels in control lung slices and slices depleted of their GSH by diethyl maleate. The esters of cysteine produced the greatest rise in lung slice cysteine. All the cysteine delivery systems were capable of replenishing GSH in lung slices previously depleted of GSH by diethyl maleate. PMID- 8494536 TI - Partition and distribution coefficients of solutes and drugs in brush border membrane vesicles. AB - Partition and distribution coefficients (log P, log D) into rat small intestinal brush border membrane (BBM) were measured for a variety of ionizable and non ionizable drugs and solutes using a novel technique. The log P values were compared with those determined with model solvents, octanol and propylene glycol dipelargonate (PGDP). Non-ionizable solutes with log P values up to 3.0 showed that octanol was a better model for partition into the BBM than PGDP. With one exception, BBM partition coefficients of greater than 3 were not observed, even for solutes with log P values in model solvents that were greater than 5. Liposomes prepared from BBM lipids, or synthetic lipid mixtures of similar composition to BBM, demonstrated similar trends in partition coefficients to the intact BBM. Two cationic drugs, Atenolol and Xamoterol were investigated for partition into BBM lipid liposomes. An apparent enhancement of log D with respect to octanol was attributed to a "surfactant-like" orientation in the membrane and an interaction of the ionized drug with anionic phospholipid head groups. The anionic drug Proxicromil shows the expected decrease in log D with increasing pH, at low NaCl concentrations. Changes in electrophoretic mobility of liposomes after incorporation of Proxicromil into them were consistent with the negative charge of the ionized drug being at the membrane surface. It was concluded that Proxicromil also associates with membranes in a "surfactant-like" orientation and that increased extraction with increasing NaCl concentrations is a result of ionic strength effects. Partition of solutes into BBM vesicles is more complex than into organic solvents and probably represents an important step in overall intestinal permeation of solutes. PMID- 8494537 TI - Picrotoxin as a potent inducer of rat hepatic cytochrome P450, CYP2B1 and CYP2B2. AB - The induction by the central stimulant picrotoxin of hepatic drug-metabolizing enzymes was studied in rats. The hepatic content of P450 and the activity of benzphetamine N-demethylation increased gradually after administration of picrotoxin dissolved in drinking water (2 mg/mL), to three-times higher levels than the initial values at the third day of treatment. The increase in benzphetamine N-demethylase activity by picrotoxin was somewhat higher than the increase produced by phenobarbital. Supporting these results, immunoblot analysis showed that CYP2B1 and 2B2 proteins in the liver microsomes were increased by picrotoxin Picrotoxinin and picrotin, which are components of the picrotoxin molecule, had the same ability to induce the hepatic activity of benzphetamine N demethylation. The liver microsomal activities of testosterone 16 alpha- and 16 beta-hydroxylation were enhanced significantly after treatment with picrotoxinin and picrotin. However, benzo[a]pyrene 3-hydroxylation, aniline 4-hydroxylation, and testosterone hydroxylations at the 2 alpha- and 7 alpha-positions were not increased by picrotoxinin and picrotin treatment. In addition to monooxygenase, significant induction of glutathione S-transferase activity for 1-chloro-2,4 dinitrobenzene and UDP-glucuronyltransferase activity for 4-hydroxybiphenyl and 4 nitrophenol was also observed by pretreatment of picrotoxin. These results clearly indicate that picrotoxin is an inducer of phenobarbital-inducible liver enzymes. PMID- 8494538 TI - Enhanced protein kinase C mediated inhibition of renal dopamine synthesis during high sodium intake. AB - The synthesis of dopamine, from L-beta-3,4-dihydroxyphenylalanine (L-DOPA), in renal tissue of rats on either a normal sodium (NS) or high sodium (HS) diet for 1 week or 6 weeks was examined. Aromatic L-amino acid decarboxylase (AAAD) activity determined in kidney homogenates in "1 week HS" (Vmax = 11.5 +/- 1.6 nmol/mg protein/hr) and "6 weeks HS" rats (Vmax = 10.6 +/- 1.5 nmol/mg protein/hr) was greater (P < 0.02) than that in "NS" rats (Vmax = 7.7 +/- 0.8 nmol/mg protein/hr). Km (microM) values in "NS", in "1 week HS" and "6 weeks HS" rats were similar. The formation of dopamine in kidney slices loaded with 100 microM L-DOPA depended exponentially on the concentration of sodium in the medium (0-160 mM). In kidney slices obtained from "1 week HS" rats the decarboxylation of added L-DOPA was significantly greater (P < 0.01) than that observed in kidney slices obtained from "NS" and "6 weeks HS" rats; the rate constant of formation of dopamine as a function of sodium concentration in the incubation medium was, however, similar in "NS" rats to that in "1 week HS" and "6 weeks HS" rats. Ouabain produced a concentration dependent decrease in the synthesis of dopamine in all three experimental groups; the magnitude of the inhibitory effect of 1.0 mM ouabain was greater in "1 week HS" rats (77% reduction; P < 0.01) than in "NS" rats (59% reduction; P < 0.01) and in "6 weeks HS" rats (23% reduction; P = 0.08). Activation of protein kinase C by phorbol 12,13-dibutyrate (PDBu) and the calcium ionophore A23187 produced a concentration-dependent reduction in the formation of dopamine in rat kidney slices, but not in kidney homogenates; the magnitude of the inhibitory effect was greater in "1 week HS" rats than in "NS" and "6 weeks HS" rats. Submaximal concentrations of PDBu (10 nM) were synergistic with the inhibitory effect of A23187 on the formation of dopamine: again, this effect was more marked in "1 week HS" rats than in "NS" and "6 weeks HS" rats. The effects of PDBu and PDBu plus A23187, but not those of A23187 alone, were antagonized in a concentration-dependent manner by d-sphingosine, a protein kinase C inhibitor. It is concluded that the increased activity of AAAD in renal tissues of rats submitted to HS intake is accompanied in "1 week HS" but not in "6 weeks HS" rats by enhanced inhibition of dopamine formation during protein kinase C activation. PMID- 8494539 TI - Paracetamol glucuronidation by recombinant rat and human phenol UDP glucuronosyltransferases. AB - Stably expressed human and rat phenol UDP-glucuronosyltransferases (UGTs) of the UGT1 complex (HlugP1, HlugP4 and 3-methylcholanthrene-inducible rat UGT1A1, the latter considered to be an orthologous enzyme to HlugP1) have been used to investigate the role of UGTs in paracetamol glucuronidation. Kinetic analysis of recombinant UGTs was compared to that of total UGT activities in liver microsomes. Paracetamol was found to be an overlapping substrate of several UGTs. It shows higher affinity for HlugP1 and rat UGT1A1 (apparent Km values of 2 and 3 mM, respectively) than for HlugP4 (Km = 50 mM) and other UGTs present in liver microsomes (Km values of > 12 mM). Glucuronidation of paracetamol with HlugP1 contrasts with that of 6-hydroxychrysene and of 4-methylumbelliferone, which are conjugated with higher affinity by HlugP4 than by HlugP1. Due to the wide tissue distribution of rat UGT1A1, paracetamol glucuronidation was also investigated in extrahepatic rat and human tissues. Paracetamol UGT activity was present and inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat kidney, lung and spleen. It was also detected in human kidney. A selective cDNA probe for exon 1 of HlugP1 cross-reacted with mRNA from both human liver and kidney. The results demonstrate that paracetamol is conjugated by HlugP1 and its rat orthologue UGT1A1 with higher affinity than by HlugP4 and other UGTs. PMID- 8494540 TI - Solubilization of active somatostatin receptors from rabbit retina. AB - Somatostatin receptors from rabbit retinal membranes were solubilized in an active form using a mixture of the detergent n-octyl b-D-glucopyranoside (OG) and CHAPS. The binding of [125I]-Try11-somatostatin to the soluble extract was saturable and of high affinity, with an apparent affinity constant (Kd) of 0.60 +/- 0.20 nM and a maximum number of binding sites (Bmax) of 80 +/- 48 fmol/mg protein. The specific binding of [125I]Tyr11-somatostatin was inhibited in a dose dependent manner only by the somatostatinergic analogs. The biochemical characteristics of both the membrane-bound and soluble receptors were studied by photoaffinity labeling techniques. Analysis by SDS-PAGE and subsequent autoradiography revealed the presence of a major protein of similar relative molecular mass (M(r) 54,000 and 57,000 for membrane and soluble sites, respectively). The photolabeling of this protein was specifically inhibited by somatostatin-28, somatostatin-14, SMS 201-995 (a synthetic octapeptide analog of somatostatin) but not by bombesin and somatostatin-28(1-14). The non-hydrolysable GTP analog guanosine-5'-O-(3-thio-triphosphate) (GTP gamma S) regulated the photolabeling of [125I]Tyr11-somatostatin to the membrane and soluble receptors. These studies describe for the first time the successful solubilization of the somatostatin receptor and the biochemical characterization of both membrane-bound and soluble receptors from rabbit retina. PMID- 8494541 TI - The inhibition of cholesterol esterification by cyclandelate in transformed mouse macrophages. AB - Cyclandelate (trimethylcyclohexanyl mandelate) inhibited cholesterol esterification in a transformed mouse macrophage cell line (J774) with a concentration of approximately 20 microM being required for half-maximal inhibition. The intact drug was required for its inhibitory action since neither of its hydrolysis products, trimethylcyclohexanol and mandelic acid, caused any inhibition even at high concentrations. The drug entered the cells very rapidly with inhibition being apparent within the shortest time possible to measure esterification (15 min after drug addition). The rate of cholesterol esterification returned to control values when drug-inhibited cells were incubated in drug-free medium indicating a rapid loss of drug from the cells. Loading of cells with cholesterol had no effect on the inhibitory action of cyclandelate, and the inhibition of esterification of cholesterol appeared to be specific, since the syntheses of phospholipid and triacylglycerol (which also involve the action of acyltransferases) were not affected by the drug. Similar inhibitions of cholesterol esterification were seen in four other cell lines, a human osteosarcoma, Chinese hamster ovary cells, a human transformed macrophage cell line (U937) and human umbilical cord vein endothelial cells, as well as in slices of pig aorta, indicating a general action in extra-hepatic tissues where the drug is not hydrolysed. PMID- 8494542 TI - Polymyxin B complexes with and cationizes low density lipoproteins. The cause of polymyxin B-induced enhancement of endocytotic catabolism of low density lipoproteins. AB - We previously reported that polymyxin B (PMB) enhances cellular catabolism of low density lipoproteins (LDLs) through a non-LDL receptor-mediated endocytotic pathway. These data were obtained mainly by using Hep G2 cells, a well differentiated human hepatoma cell line. In the current study, we explore the mechanisms of PMB-mediated endocytotic catabolism of LDL. We found that PMB enhanced LDL catabolism also in homozygous familial hypercholesterolemia fibroblasts, thereby establishing that PMB-mediated cellular catabolism of LDL does not involve LDL receptors. By using [14C]sucrose, and ligands for the asialoglycoprotein (ASGP) receptors, possibilities were excluded that PMB enhances cellular endocytosis of LDL, by inducing a general increase of cellular pinocytic activity or by causing endocytosis of LDL via the ASGP receptors in Hep G2 cells. We further show, by using polymyxin B coupled Sepharose 4B (PMB Sepharose 4B) beads, that PMB binds to LDL to form a complex. This binding was tight, and changes in pH and salt concentrations had no significant effect on the binding, but unlabelled LDL competed with 125I-LDL to bind to PMB-Sepharose 4B. Urea and endotoxins decreased this binding, suggesting that PMB binds to LDL at least partially through hydrophobic interactions. Agarose gel electrophoresis of PMB-LDL indicates that PMB cationizes LDL. In conclusion, PMB binds to LDL to form a PMB-LDL complex presumably through interactions between lipid groups. This endows LDL with positive charges, which enhances LDL binding to negatively charged cell membranes, and such bound LDL is rapidly internalized through absorptive endocytosis. PMID- 8494543 TI - Modulation of the insulinotropic action of glibenclamide and glimepiride by nutrient secretagogues in pancreatic islets from normoglycemic and hyperglycemic rats. AB - In perifused pancreatic islets from euglycemic rats, the secretory response to either glibenclamide or glimepiride (1.0 microM each) increases as a function of the concentration of D-glucose (2.8-16.7 mM) present in the perifusion medium. On the contrary, the sulfonylurea-induced increment in 45Ca efflux from prelabeled islets decreases at increasing concentrations of the hexose. Neither glibenclamide nor glimepiride affect D-glucose metabolism in isolated islets, as judged from the production of 3HOH from D-[5-3H]glucose or the generation of 14CO2, as well as 14C-labeled amino acids and acidic metabolites, from D-[3,4 14C]glucose, D-[2-14C]glucose and D-[6-14C]glucose. The insulinotropic action of the hypoglycemic sulfonylureas is not impaired in islets prepared from rats infused for 48 hr with a hypertonic solution of D-glucose. The dimethyl ester of succinic acid is more efficient than D-glucose in supporting the insulin releasing effect of glibenclamide or glimepiride. Thus, although the insulinotropic action of hypoglycemic sulfonylureas appears unaffected in a model of B-cell glucotoxicity, a potentiation of their secretory effects might be expected, in non-insulin-dependent diabetes, from the combined administration of succinic acid methyl ester. PMID- 8494544 TI - Tamoxifen inhibits lipid peroxidation in cardiac microsomes. Comparison with liver microsomes and potential relevance to the cardiovascular benefits associated with cancer prevention and treatment by tamoxifen. AB - Tamoxifen and 4-hydroxytamoxifen were both good inhibitors of iron-dependent lipid peroxidation in rat cardiac microsomes. Tamoxifen was also a good inhibitor of lipid peroxidation in liposomes prepared from the phospholipid obtained from rat liver microsomes. In a modified rat liver microsomal system containing a sufficiently low amount of peroxidizable phospholipid to make it comparable with the rat cardiac microsomal system, tamoxifen and 4-hydroxytamoxifen were of similar effectiveness as in the cardiac system. Tamoxifen is known to lower serum cholesterol levels, and the findings reported here indicate that the drug might also protect heart cell membranes against peroxidative damage. Potential cardioprotective and antiatherosclerotic benefits of tamoxifen are discussed in relation to the drug's use in cancer prevention and treatment. PMID- 8494545 TI - Kinetic studies on 2',2'-difluorodeoxycytidine (Gemcitabine) with purified human deoxycytidine kinase and cytidine deaminase. AB - Phosphorylation of cytosine analogs by deoxycytidine kinase (dCK) and deamination by cytidine deaminase (CDA) are two important processes in the activation and elimination of these drugs. We have investigated the kinetic parameters of 2',2' difluorodeoxycytidine (dFdC) using purified enzymes from human cells. Deoxycytidine (CdR) and dFdC had Km values of 1.5 and 4.6 microM for dCK, respectively. Feedback inhibition of dCK by deoxycytidine 5'-triphosphate (dCTP) was also studied. Our results show that dCTP produced a greater inhibition of the phosphorylation of dFdC than CdR with concentrations of dCTP ranging from 1 to 25 microM. dFdC was a good substrate for CDA. Kinetic studies with this enzyme gave Km values for CdR and dFdC of 46.3 and 95.7 microM, respectively. The effect of competitive inhibitors of CDA on the deamination of dFdC was also investigated. Diazepinone riboside was a more potent inhibitor than tetrahydrouridine using either CdR or dFdC as the substrate. Inhibitors of CDA could be useful in clinical trials in patients with cancer to increase the chemotherapeutic effectiveness of dFdC. PMID- 8494546 TI - Transport, distribution space and intracellular concentration of the anti inflammatory drug niflumic acid in the perfused rat liver. AB - Transport and distribution space of niflumic acid in the perfused rat liver were investigated employing the multiple-indicator dilution technique with constant infusion of the drug (step input). Niflumic acid permeated the cell membrane in both directions at very high rates and its distribution in the cellular space was flow-limited; at least at 37 degrees, the rates of influx and efflux could not be measured. Dissociation of the niflumic acid-albumin complex also occurred at very high rates. The apparent space of distribution of niflumic acid in the liver depended on the concentration of the drug and varied between 4.37 (1 mM) and 43.5 (10 microM) times the water space; even with 90% extracellular binding to albumin, the apparent space of distribution of niflumic acid was 5.1 times greater than the water space. The high apparent spaces of distribution reflected the high intracellular concentrations. The ratio of intracellular bound plus free concentration to the extracellular bound plus free concentration (Ci/Ce) varied between 6.62 (1 mM portal niflumic acid) and 71.0 (10 microM portal niflumic acid). Metabolic transformation depended on the concentration of the free form. Intracellular binding is probably the major reason for the high concentration of the drug in the hepatic tissue. PMID- 8494547 TI - Effects of polyunsaturated fatty acids on the efficacy of antineoplastic agents toward L5178Y lymphoma cells. AB - Modification of cultured lymphoma cells (L5178Y) with individual unsaturated fatty acids [oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (alpha LNA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] influenced cell growth and the responses of the cells to the chemotherapeutic agents doxorubicin (DRN), dexamethasone (DEX) and mitomycin-C (MTC). Cell proliferation generally decreased following modification with highly unsaturated fatty acids (> 10 microM). The effects of drugs on growth varied with the type of fatty acid. Preincubation with alpha-LNA enhanced survival of L5178Y cells exposed to DRN. Modification with AA, EPA or DHA (> 10 microM) reduced cell proliferation, particularly when cells were subsequently exposed to 50 or 100 nM DRN. There was no consistent relationship between fatty acid chain length, degree of unsaturation, and survival of cells when exposed to DEX or MTC. The data showed that modification of cultured L5178Y cells with highly unsaturated fatty acids, particularly DHA, enhances the toxic action of chemotherapeutic agents. PMID- 8494548 TI - Inhibition of human leucocyte elastase by fatty acyl-benzisothiazolinone, 1,1 dioxide conjugates (fatty acyl-saccharins). AB - Derivatives of benzisothiazolinone 1,1-dioxide (saccharin) N-acetylated with aliphatic and aromatic substituted aliphatic acyl groups were prepared. The inhibitory activity of the compounds was assayed against human leucocyte elastase (EC 3.4.21.37) and several other proteases. The IC50 values for inhibition of the human leucocyte elastase decreased with increasing length of the acyl residue, and reached a minimum value at C16 (2 microM). This phenomenon and the decrease of the inhibition by surfactants or by saturation of the enzyme with palmitic acid, indicates that in addition to acylation, hydrophobic interactions are also involved in the inhibition of this proteinase by compounds substituted with acyl groups containing at least 12 carbon atoms. The inhibitory activity of N palmitoyl-benzisothiazolinone 1,1-dioxide (palmitoyl-saccharin) is about 14 times higher toward human leucocyte elastase than for thrombin (EC 3.4.21.5), and several hundred times, compared to porcine pancreatic elastase (EC 3.4.21.36) and to plasmin (EC 3.4.21.7). Fatty acylated saccharin derivatives were seen to bind in a saturable fashion to insoluble elastin, and decreased the susceptibility of this protein to hydrolysis by human leucocyte elastase. PMID- 8494549 TI - Effects of inhibitors of spermidine synthase and spermine synthase on polyamine synthesis in rat tissues. AB - Several inhibitors of aminopropyltransferases, developed recently in this laboratory, were tested for their specificity by measuring their effects on six enzyme activities related to polyamine biosynthesis and interconversion. Two of them, trans-4-methylcyclohexylamine (4MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA), selectively and potently inhibited the activities of spermidine synthase and spermine synthase, respectively. They were subjected to in vivo studies using rats. Oral administration of 4MCHA or APCHA dissolved in drinking water (0.02 and 0.1%) available ad lib. for a period of 10 days or 4 months caused a specific and marked decrease in spermidine or spermine in tissues (such as a 95% decrease) with a compensatory increase of spermine or spermidine, respectively, but without any observable change in the growth of the treated rats. Also, with extreme reduction of spermidine or spermine, when their sum was approximately constant, the activity of S-adenosyl-methionine decarboxylase in these tissues was enhanced significantly with no change in the activity of ornithine decarboxylase. These results suggested a separate role for spermidine or spermine in the in vivo enhancement of S-adenosylmethionine decarboxylase activity. PMID- 8494550 TI - Inhibition of phosphatidylcholine secretion by stilbene disulfonates in alveolar type II cells. AB - Various agents stimulate the secretion of lung surfactant from alveolar type II cells by increasing intracellular Ca2+, cyclic adenosine-3':5'-monophosphate (cAMP), or diacylglycerol. A few agents, including the purified surfactant protein A, are known to inhibit the secretion by an unknown mechanism. In the present study, we demonstrated that stilbene disulfonic acids, 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid (SITS), are potent but reversible inhibitors of lung surfactant secretion. The inhibition was concentration dependent, and the EC50 was 5 microM for DIDS and 50 microM for SITS. The inhibition was not specific to agonists for any one type of receptor, and was also observed for secretion stimulated by 8-bromo-cAMP, or tetradecanoyl phorbol acetate, suggesting that the site of inhibition was distal to the generation of intracellular second messengers. This was also supported by the failure of DIDS to block the stimulus-mediated increase in diacylglycerol content of type II cells. Further, DIDS and SITS were also inhibitory for basal secretion. Based on the reversibility of inhibition and the fact that inhibition was observed with both basal and stimulated secretion, we suggest that stilbene disulfonic acids affect a component of the exocytosis process that occurs at or near the plasma membrane. PMID- 8494551 TI - Analysis of estrogen receptor interaction with tertiary-structured estrogen responsive elements. AB - An initial crucial step in estrogen activation of gene expression is the interaction of the estrogen receptor with a specific nucleotide sequence [estrogen responsive element (ERE)]. Previously, we found that the estrogen receptor binds preferentially and with high affinity to the lower strand of the rat prolactin imperfect ERE which contains tertiary structure (Lannigan DA and Notides AC, Proc Natl Acad Sci USA 86: 863-867, 1989). Using perfect and imperfect EREs from the upstream region of the chicken vitellogenin II gene, we have now extended our findings and have determined that the estrogen receptor preferentially interacts with either perfect or imperfect EREs which contain tertiary structure. A similar structure is present in a synthetic 42 bp oligonucleotide corresponding to the lower strand of a perfect ERE with flanking sequences from the rat prolactin ERE. Moreover, deviations from the ERE consensus sequence decrease the binding of the estrogen receptor to the tertiary-structured ERE. We also have determined that ERE flanking sequences contribute to the affinity of the receptor for the tertiary-structured ERE. Furthermore, ERE flanking sequences can influence the types of interactions that the estrogen receptor makes with the tertiary-structured ERE. PMID- 8494552 TI - Aspects of the cellular pharmacology of N-l-leucyldoxorubicin in human tumor cell lines. AB - We have compared the cytotoxicity, incorporation and metabolism of doxorubicin (dox) and N-l-leucyldoxorubicin (leu-dox) in two human tumor cell lines in culture, the MCF-7 breast cancer line and the K562 leukemia line, and their dox resistant counterparts. Dox was 3-4-fold more cytotoxic than leu-dox in the MCF-7 lines, and 7-10-fold in the K562 lines. This could be explained by differences in cell incorporation of the drugs, which differs by the same proportion as the cytotoxicities in the various cell lines, rather than by differences in biotransformation of leu-dox into dox, which is similar in all of the cell lines. PMID- 8494553 TI - 50-Hz magnetic field exposure system for small animals. AB - The design, construction, and results of evaluation of an animal-exposure system for the study of biological effects of extremely low frequency (ELF) magnetic fields are described. The system uses a square coil arrangement based on a modification of the Helmholtz coil. Due to the cubic configuration of this exposure system, horizontal and vertical magnetic fields as high as 0.3 mT can be generated. Circularly polarized magnetic fields can also be generated by changing the current and phase difference between two sets of coils. Tests were made for uniformity of the magnetic field, stray fields, sham-exposure ratio of stray field, changes of temperature and humidity, light intensity and distribution inside the animal-housing space, and noise due to air-conditioning equipment. Variation of the magnetic field was less than 2% inside the animal housing. The stray-field level inside the sham-exposure system is less than 2% of experimental exposure levels. The system can be used for simultaneous exposure of 48 rats (2 to a cage) or 96 mice (4 to a cage). PMID- 8494554 TI - Misclassification of ELF occupational exposure resulting from spatial variation of the magnetic field. AB - The adequacy of a single hip- or chest-worn magnetic field dosimeter to reliably classify subjects with respect to their occupational ELF magnetic field exposure is investigated. Hip-worn dosimeters consistently underestimate both whole-body average exposure and head exposure, tentatively regarded here as two possible definitions of the "true" exposure measurement. The approximate resulting bias in the relative risk estimate in hypothetical case-control studies is evaluated. A chest-worn dosimeter is found to be generally superior to a hip-worn one in assessing exposure during the occupational tasks considered here. PMID- 8494555 TI - Effects of magnetic fields on mammary tumor development induced by 7,12 dimethylbenz(a)anthracene in rats. AB - A series of epidemiological studies have indicated associations between exposure to magnetic fields (MFs) and a variety of cancers, including breast cancer. In order to test the possibility that MF acts as a cancer promoter or copromoter, four separate experiments have been conducted in rats in which the effects of chronic exposure to MFs on the development of mammary tumors induced by 7,12 dimethylbenz(a)anthracene (DMBA) were determined. Female rats were exposed in magnetic coils for 91 days (24 h/day) to either alternating current (AC; 50 Hz) MF or direct current (DC)-MF. Magnetic flux density of the DC-MF was 15 mT. Two AC-MF exposures used a homogeneous field with a flux density of 30 mT (rms); one used a gradient field with flux density ranging from 0.3-1 microT. DMBA (5 mg) was administered orally at the onset of MF exposure and was repeated thrice at intervals of 1 week. In each experiment, 18-36 animals were exposed in 6 magnetic coils. The same number of rats were used as sham-exposed control. These control animals were treated with DMBA and were placed in dummy coils in the same room as the MF-exposed rats. Furthermore, groups of age-matched rats (reference controls) were treated with DMBA but housed in another room to exclude any MF exposure due to the magnetic stray field from the MF produced by coils. At the end of the exposure or sham-exposure period, tumor number and weight or size of tumors were determined at necropsy. Results were as follows: In sham-exposed animals or reference controls, the tumor incidence varied between 50 and 78% in the 4 experiments. The average number of mammary tumors per tumor-bearing animal varied between 1.6 and 2.9. In none of the experiments did MFs significantly alter tumor incidence, but in one of the experiments with AC-MF exposure at 30 mT, the number of tumors per tumor-bearing animal was significantly increased. Furthermore, exposure to a DC-MF at 15 mT significantly enhanced the tumor weight. Exposure to a gradient AC-MF at 0.3-1 microT exerted no significant effects. These experiments seem to indicate that MFs at high flux densities may act as a promoter or copromoter of breast cancer. However, this interpretation must be considered only a tentative conclusion because of the limitations of this study, particularly the small sample size used for MF exposure and the lack of repetition of data. PMID- 8494556 TI - Repeatability of measurements of residential magnetic fields and wire codes. AB - Several epidemiological studies have been based on wire codes (i.e., categories of electrical wiring configurations near residences) or on in-home spot measurements of magnetic flux density (MFD) as surrogates for short- and long term exposure of children and adults to residential magnetic fields. We used wire code and MFD measurements that were made in 81 Colorado homes in 1985 and again in 1990 to assess their repeatability over periods of 0-24 h and 5 years. These homes, a subset of those lived in by subjects from the case-control study of Savitz et al. [Am J Epidemiol 128:21-38, 1988], were divided into four approximately equally sized groups that were differentiated by wire code and by case-control status. Eight homes were assigned wire codes in 1990 that differed from the 1985 coding of Savitz and colleagues [1988]; of these, seven were coded as high-current configuration (HCC) and one as low-current configuration (LCC) in 1985. Overall, 37 homes were coded as HCC in 1990 compared with 38 homes in 1985. Coding differences were due to differing distance measurements (four homes), differing "thick" vs. "thin" categorization of primary-distribution line conductor sizes (two homes), differing "first-span" vs. "second-span" categorization of secondary wires (one home), and physical changes in proximate electrical wiring (one home). Coefficients of correlation between MFD spot measurements that were separated in time by 0-24 h range between 0.70 and 0.90. The coefficient between spot measurements made in 1985 and then again in 1990 is 0.70. These coefficients are similar for HCC and LCC homes and do not depend on whether residential appliances were turned on or off. The data show (at least for the portion of Colorado studied) that residential wire code and, more surprisingly, spot MFD measurements, are fairly reliable over 0-24-h and 5-year periods. PMID- 8494557 TI - Use of a spreadsheet program to calculate the electric field/current density distributions induced in irregularly shaped, inhomogeneous biological structures by low-frequency magnetic fields. AB - A commercially available spreadsheet program is used on a microcomputer to calculate the electric field/current density distributions induced in irregularly shaped, inhomogeneous objects by low-frequency magnetic fields. A finite difference method is applied to an impedance grid that represents the object being modeled. This approach is validated by comparison with 1) the analytical results of an eccentric cylinder model and 2) measurements made on a square dish containing a saline solution and square, insulating inclusions. Application of the method is also made to a culture dish with a layer of sediment exposed to a horizontal magnetic field. PMID- 8494558 TI - Design and characterization of a system for exposure of cultured cells to extremely low frequency electric and magnetic fields over a wide range of field strengths. AB - A system is described that is capable of producing extremely low frequency (ELF) magnetic fields for relatively short-term exposure of cultured mammalian cells. The system utilizes a ferromagnetic core to contain and direct the magnetic field of a 1,000 turn solenoidal coil and can produce a range of flux densities and induced electric fields much higher than those produced by Helmholtz coils. The system can generate magnetic fields from the microtesla (microT) range up to 0.14 T with induced electric field strengths on the order of 1.0 V/m. The induced electric field can be accurately varied by changing the sample chamber configuration without changing the exposure magnetic field. This gives the system the ability to separate the bioeffects of magnetic and induced electric fields. In the frequency range of 4-100 Hz and magnetic flux density range of 0.005-0.14 T, the maximum total harmonic distortion of the induced electric field is typically less than 1.0%. The temperature of the samples is held constant to within 0.4 degrees C by constant perfusion of warmed culture medium through the sample chamber. PMID- 8494559 TI - Effects of 45-Hz magnetic fields on the functional state of the human brain. AB - The influence of sinusoidal 45-Hz magnetic fields on the brain functions of 20 volunteers was investigated in a double-blind study using spectral analysis of EEG and measurements of Omega potentials and reaction time (RT). The field strength was 1,000 A/m (1.26 mT) and the duration of exposure was 1 h. Ten volunteers were exposed to a continuous field and ten received an intermittent exposure (1 s on/l s off). Each person received one real and one sham exposure. One half of the volunteers got the real exposure first and the sham treatment after at least 24 h. For the rest, the sequence was inverse. The measurements of EEG, omega potentials and RT were performed before and after each exposure. Several statistically significant changes were observed, most of them after intermittent exposure. In the EEG, an increase of alpha (7.6-13.9 Hz) activity and a decrease of delta (1.5-3.9 Hz) activity were observed. Beta waves (14.2-20 Hz) increased in the frontal derivations as did the total power in occipital derivations. The mean and peak frequencies of EEG increased mainly in the frontal derivations. No direct effects on RT were seen. Learning to perform the RT test (decrease of RT in repeated trials), however, seemed to be affected by the exposure. The persons who received real exposure first learned more slowly than those who got sham exposure first. Further experiments are necessary to confirm the findings and for understanding the mechanisms of the effects. PMID- 8494560 TI - Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats. AB - We sought to determine whether a 6-week exposure to a 50-Hz rotating magnetic field influences melatonin synthesis by 11-18 week-old Wistar-King male rats. Rats were exposed continuously to a rotating magnetic field at 1, 5, 50, or 250 microT (spatial vector rms) for 6 weeks, except for twice-weekly breaks of about 2 h for cleaning of cages and feeding. The rats were housed in exposure and sham exposure facilities, which were located in the same room, under a 12:12 light dark photoperiod (lights on at 06:00 h). The room was constantly illuminated by 4 small, dim red lights (< 0.07 lux in dark period). Levels of plasma and pineal gland melatonin were determined by radioimmunoassay. A significant decrease of melatonin was observed between the control group and groups exposed to a magnetic field at a flux density in excess of 1 microT during the night time, but no statistical differences were found among the exposed groups. These results indicate that subchronic exposure of albino rats to a 50-Hz rotating magnetic field influences melatonin production and secretion by the pineal gland. PMID- 8494561 TI - [Amidation of proteins and peptides with carboxypeptidase Y]. AB - The native and modified carboxypeptidase Y-catalyzed reaction of acyl transfer of acylamino acid and peptide residues from the corresponding esters to ammonia was studied. Use of the modified carboxypeptidase Y increased the yield of the resulting product. Calcitonin-Leu was transformed into human calcitonin. PMID- 8494562 TI - [Bse118 I--a new isoschizomer of restriction endonuclease Cfr10 I, isolated from the thermophilic bacterium Bacillus coagulans]. PMID- 8494563 TI - [Bco116 I--a new isoschizomer of restriction endonuclease KSP632 I]. PMID- 8494564 TI - [Preparation and bacterial expression of a mutant gene for human lymphotoxin]. AB - Using the oligonucleotide directed mutagenesis, a human lymphotoxin (TNF beta) mutant gene lacking 21 N-terminal codons has been obtained. Recombinant plasmid pLT21 for expression of the mutant gene has been constructed. The mutant gene in the plasmid was placed under control of a tandem of constitutive promoters from coliphage T7. A simple procedure for isolation of recombinant protein was developed. The procedure allows to obtain the highly purified biologically active mutant protein with a good yield. During biosynthesis the recombinant protein undergoes a posttranslational processing resulted in the cleavage of N-terminal methionine and leucine residues. PMID- 8494565 TI - [Preparation of recombinant metastazin and characteristics of it]. AB - The recombinant mts-1 protein has been obtained with the use of the pMAL-c expression vector. This protein was shown to bind calcium ions and interact with melittin, a polypeptide from bee venom. PMID- 8494566 TI - [Structure of the repeating unit of the intracellular polysaccharide from Mycobacterium convolutum 240]. AB - An acidic extracellular polysaccharide composed of D-glucose, L-fucose, D glucuronic acid and pyruvic acid residues has been isolated from the Mycobacterium convolutum culture fluid. On the basis of methylation analysis and 13C NMR data, the structure of the repeating unit of the polysaccharide was deduced as follows: -->3)-beta-D-Glcp-(1-->4)-beta-D-GlcpA-(1-->4)-alpha-L-Fucp- (1--> [formula: see text] PMID- 8494567 TI - [Porphyrin derivatives of oligonucleotides. I. Synthesis of oligonucleotide derivatives bearing 2,4-di(alpha-(2-hydroxyethoxy)ethyl)- deuteroporphyrin IX or a metal complex of it and study of the oxidative modification of DNA by these derivatives]. AB - A method for coupling 2,4-di[alpha-(2-hydroxyethoxy)ethyl] deuteroporphyrin dimethyl ether (IX), DDPOH and its complexes with metals to the 5'- or 3'-end of oligonucleotides was elaborated. In the presence of an oxidizing agent (H2O2), Fe(III)DDP-derivatives of oligonucleotides modified single-stranded DNA. The reaction was strictly site-specific and occurred at two neighbouring guanosine residues. A few types of modification were observed: cross-linking, modification leading to DNA cleavage upon piperidine treatment, and direct chain scission. The total modification yield reached 90%. Covalent attachment of Fe(III)DDP-group to oligonucleotides increased the efficiency of their uptake and the melting temperature of their complementary complexes. PMID- 8494568 TI - [Oligodeoxyribonucleotides containing 2'-amino-2'-deoxypyrimidine nucleosides]. AB - The synthesis, by means of the standard phosphoramidite chemistry, of modified oligodeoxynucleotides (5-20 residues) containing 2'-amino-2'-deoxypyrimidine nucleosides has been carried out, and their ability to form duplexes with complementary DNA has been investigated. A high reactivity of such compounds in N acylation was shown. PMID- 8494569 TI - [Interaction of vitamin E (alpha-tocopherol) with oxygenated fatty acid derivatives]. AB - Fluorescence spectra of alpha-tocopherol and its mixtures with oxygenated derivatives of fatty acids--linoleic acid hydroperoxide, hydroxylinoleic and ricinoleic acids--were investigated in terms of the excitation and emission dependence on the concentration of components in acetonitrile solution. In accordance with our results, formation of the alpha-tocopherol excimer and exciplex with the oxygen-containing derivatives of polyunsaturated fatty acids was suggested. The character of the interaction between components of the excited complexes and their possible role in peroxidation of lipids are discussed. PMID- 8494571 TI - DNA strand breaks in cells with DNA repair deficiency after halothane exposure in vitro. AB - Halothane (CAS 151-67-7) induced DNA strand breaks in isolated lymphocytes of two patients with a deficient DNA repair (xeroderma pigmentosum). In lymphocytes (resting cells) of healthy human donors and in L 5178 Y cells (proliferating cells) of mouse lymphoma, halothane did not induce demonstrable DNA strand breaks. The cells were exposed to 1.0 vol/% halothane for 60 min, and the DNA strand breaks were demonstrated by alkaline elution. The results suggest a possible genotoxic side effect of halothane in patients with deficiency in DNA repair. PMID- 8494570 TI - Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. AB - We examined the relative potencies of zonisamide (CAS 68291-97-4) to acetazolamide in inhibiting carbonic anhydrases in human erythrocytes and purified human carbonic anhydrase I and II in vitro and found them to be about 1/150, 1/8 and 1/188, respectively. The IC50 values of zonisamide and acetazolamide for the inhibition of erythrocyte enzymes were close to those of purified carbonic anhydrase II. This result indicates that zonisamide actually differs from acetazolamide in their actions on the physiological events which are coupled with CO2 hydration in vivo. PMID- 8494572 TI - Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations. AB - The working rat heart model was used for 31P nuclear magnetic resonance (NMR) studies during normoxia, hypoxia and reoxygenation. Aortic flows of about 35 ml/min could be achieved which equals 65% of the values obtained outside the NMR magnet. Addition of dihydrolipoic acid (DHL) at a concentration of 0.3 mumol/l during hypoxia accelerated the recovery of aortic flow and stabilized it during reoxygenation. During hypoxia, inorganic phosphate contents (Pi) were significantly higher in controls. The phosphate shift indicated a pH decrease in control to 6.98, in DHL treated hearts the calculated pH was 7.15. During both hypoxia and reoxygenation, the phosphocreatinine (PCr) contents were higher in the DHL treated hearts than in controls. In the controls, saturation transfer measurements revealed a decrease of the flux PCr-->ATP during initial reoxygenation, whereas after addition of 0.3 mumol/l of DHL during hypoxia creatine kinase flux remained constant or increased. In isolated rat heart mitochondria, creatine kinase activities were measured under saturating and non saturating concentrations of PCr. An increase in activity was observed under low PCr (non-saturating) conditions in the presence of 0.7 nmol DHL per mg of protein. At higher concentrations of DHL, creatine kinase activity was increased under all conditions. An increase in ATP synthesis in the working rat heart under influence of DHL is corroborated by NMR spectroscopy. PMID- 8494573 TI - Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 2nd communication: tissue distribution in rats. AB - The distribution of radioactivity in rats after intravenous or oral administration of 14C-labelled N-N'-dicyclopropyl-methyl-piperazine dichlorhydrate (14C-Ino 2628-CZ) demonstrated that the labelled compound was widely distributed in the body. An important diffusion of the isotope was found in the central nervous system, the gastric mucosa and several glands. Only small amounts of radioactivity were found in these organs 24 h after dosage. PMID- 8494574 TI - Hypertensive effects and structure-activity relationships of 5-omega-aminoalkyl isoxazoles. AB - Structure-activity and dose-response relationships of a series of novel 5-omega aminoalkyl and 5-omega-amino-heteroalkyl isoxazoles on blood pressure and heart rate of Sprague-Dawley rats have been investigated. To differentiate between peripheral and central cardiovascular actions of those compounds a pithed rat and anaesthetized rat preparation was used. Most of the compounds investigated exhibit potent hypertensive actions. The hypertensive effects of the tested compounds is depending on the amphiphilic character of the isoxazoles represented by a basic moiety in a definite distance to the phenyl substituents. To achieve high pharmacological activity a fully flexible side chain is requested, too. Possible mechanisms of action are discussed. PMID- 8494575 TI - Disposition of a new heparan sulfate with fibrinolytic activity in the rat. AB - A fluoresceinated derivative of a new heparan sulfate fraction (HS) was administered by intravenous route to rats. The compound was similar to the unlabelled compound and biologically active. After i.v. injection, pharmacokinetic parameters were analyzed and discussed according to a two compartment open model. In addition, experiments performed with the unlabelled compound indicate that the HS is absorbed through the intestinal mucosa, reaches the highest plasmatic concentration after 90 min and is partially recovered, unmodified, in urine. Other sets of experiments, in vitro, show that the compound is degraded in the presence of hepatic microsomal preparation while it is not metabolized by plasma, confirming that the liver plays an important role in the metabolism and consequently on the activity of the compound. The overall results are in accordance with the fibrinolytic and antithrombotic activity of HS administered orally to animals and man. PMID- 8494576 TI - Efficacy of glutathione for treatment of fascioliasis. An investigation in the experimentally infested rat. AB - Liver fluke infection (Fasciola hepatica) depresses the drug-metabolizing capacity of the hepatic mixed function oxidase (MFO) and glucuronosyltransferase (GT) enzyme systems, throughout a free radicals mediated lipid peroxidation process. Glutathione (GSH, CAS 70-18-8) administered chronically (100 mg/kg i.p. once daily for 40 days) to experimentally infested rats from the onset to the maximal development of the infection (40th day), greatly reduced the damage to membrane lipids of the liver tissue (primary event of the disease), as judged by malonic dialdehyde (MDA) content (decreased by 80%) and diene conjugation absorption (delta E 1% value falls from 1.94 to 0.67). As a consequence, serum glutamate-oxaloacetate (GOT) and glutamate-pyruvate (GPT) transaminases levels, liver GSH and phospholipid (PL) contents, cytochrome P-450, NADPH-cytochrome-P 450 reductase and some typical cytochrome P-450-dependent activities (p nitroanisole O-demethylase, aniline hydroxylase, as well as UDP glucuronosyltransferase (GT) activity, all markedly affected in the acute stage of the disease, tend to recover to the control values. The efficacy of GSH in preventing the impairment of the hepatic drug metabolizing capacity was also demonstrated by using as substrate the widely employed flukicidal agent nitroxinil (3-iodo-4-hydroxy-5-nitrobenzonitrile). The in vitro cytochrome P-450 dependent nitroxinil detoxification (reduction to 3-iodo-4-hydroxy-5 aminobenzonitrile), drastically impaired in infested animals (-80%), is markedly restored (3-fold increase) in GSH-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494577 TI - Safety and tolerance of trospium chloride in the high dose range. AB - The safety and tolerance of increasing single oral doses of 20, 40, 80, 120, 180, 240 and 360 mg trospium chloride (Spasmo-lyt, CAS 10405-0204) were investigated in 29 healthy male volunteers in a double-blind placebo-controlled study. Blood pressure, heart rate, ECG, pupillary diameter, salivary secretion, and subjective reports of tolerance revealed no essential differences between placebo and trospium chloride in doses up to 120 mg. Starting with single doses of 180 mg, anticholinergic effects were observed with increasing intensity, i.e., dilatation of the pupils, reduction of salivary flow, and increase of heart rate. While the highest administered dose of 360 mg trospium chloride did not cause any relevant changes of vital parameters (blood pressure, pulse, ECG), it was subjectively rated as quite unpleasant. The data show that trospium chloride is well tolerated in single oral doses well above the current therapeutic daily dose of up to 40 mg. PMID- 8494578 TI - Synthesis of new 5-substituted pyrazolo[1,5-d][1,2,4]-triazine derivatives and their analgesic, anti-inflammatory and antipyretic properties. AB - A series of 2-aryl-4-oxo-pyrazolo[1,5-d][1,2,4]triazines substituted in the 5 position by aminoalkyl or benzoyl moieties was synthesized and evaluated for analgesic activity. The structures of new triazine derivatives were confirmed by IR, 1H-NMR spectra and by elementary analysis. In the phenylbenzoquinone induced writhing test, only 3,3a-dihydropyrazolo triazines substituted by an arylpiperazinylmethyl group exhibited potent analgesic effect. In addition, these compounds possessed significant anti-inflammatory and antipyretic properties. A desaturation in 3,3a positions or other groups than arylpiperazinylmethyl moieties notably decreased analgesic effects. PMID- 8494579 TI - [Transcutaneous absorption of non-steroidal antirheumatics. Clinical study under a new model for investigation of pharmacokinetics]. AB - The feasibility of the bilateral vein stripping model for the investigation of the transcutaneous absorption of a non-steroidal antirheumatic drug (NSAID) was examined. After application of a 1% solution of indomethacin (Elmetacin, CAS 53 86-1) at one leg (steady state) plasma and vein tissue of both sides was taken at the same time. The mean indomethacin plasma levels of 19 female patients were 7 ng/ml, in the vein tissue of the application side 280 ng/g and at the opposite side 80 ng/g. The tissue levels in the veins are in the same range as in the target tissues of transcutaneous antirheumatic therapy. Therefore the model is considered useful for the investigations of the pharmacokinetics of topically applied NSAID. PMID- 8494580 TI - Intranasal treatment of perennial allergic rhinitis. Comparison of azelastine nasal spray and budesonide nasal aerosol. AB - The efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.d.) and budesonide (CAS 51333-22-3) nasal aerosol (0.05 mg/nostril b.i.d.) were compared in a 6-week, multicentre, parallel group study of 193 patients suffering from perennial allergic rhinitis. Total rhinitis symptoms complex (TSC) scores derived from 10 rhinitis symptoms improved during treatment by a mean of 11.4 +/- 6.8 with azelastine and 10.8 +/- 6.4 with budesonide. Response rates, defined as a decrease in TSC of at least 50% at the end of therapy, was 79% with azelastine and 73% with budesonide. There were no significant differences between the treatment groups with respect to either target variable. Objective measurements of nasal flow rate showed a return to normal values during the 6-week therapy. Signs of rhinitis identified by rhinoscopic examination improved in parallel to symptoms. Both medications were well tolerated. The incidence of adverse events of possibly causal relationship to therapy was low. The most frequent event in azelastine treated patients was the experience of an "unpleasant" taste or smell. Occasional epistaxis occurred in both treatment groups but more frequently with budesonide. Results indicate that with the dose used azelastine nasal spray is an effective treatment for perennial allergic rhinitis comparable to that of budesonide nasal aerosol. PMID- 8494581 TI - Antiproliferative activity of retinoic acid and some novel retinoid derivatives in breast and colorectal cancer cell lines of human origin. AB - Antiproliferative activities of all-trans-retinoic acid (RA, CAS 302-79-4) and some retinoid derivatives (all-trans-retinyl-beta-D-glucuronide (RYG), methyl-(1 O-retinoyl-beta-D-glucopyranoside) uronate (MRG), all-trans-retinoic acid beta-D galactopyranosyl ester (RGA), and all-trans-retinoic acid beta-D-glucopyranosyl ester (RGU)) were determined by microculture tetrazolium assay (MTT assay) and cell counting by Coulter Counter (CC) in breast (MCF7, MDA MB 231) and colon (SW 948) cancer cell lines of human origin. RA, MRG, RGU, and RGA (5, 25 mumol/l) were significantly more growth-inhibitory in MCF7 cells, which are known to be cellular retinoic acid-binding protein (cRABP) and cellular retinol binding protein (cRBP) positive, than in MDA MB 231 cells which are cRABP and cRBP negative. RYG was active only in MDA MB 231 cells. RA, MRG, RGA and RGU (25 mumol/l) stimulated the proliferation of SW 948 cells as determined by CC, whereas the MTT assay indicated an inhibition of cell growth. PMID- 8494582 TI - Efficacy of tromantadine and aciclovir in the topical treatment of recurrent herpes orofacialis. Comparison in a clinical trial. AB - In a double-blind study, 198 patients experiencing recurrent herpes orofacialis were randomly assigned to treatment with either tromantadine hydrochloride (ViruMerz Serol, CAS 53783-83-8) or aciclovir. All patients performed an up to 5 day course of topical treatment beginning on average within 2 h after the first signs of recurrence. The herpes efflorescences and symptoms were assessed daily by the same physician for 14 days, except on weekends, and by the patients each day during the whole observation time. Rapid healing was achieved with both medications. Efficacy was assessed by rating the course of vesicle eruptions, duration until beginning of incrustation and the clinical course of the symptoms (burning, tension, pain). Equivalence between the medication groups was shown by comparative analysis of all evaluation criteria. The global efficacy and tolerability of both medications was rated by the physician as well as by the patients as "good" or "very good" in more than 80% of the cases. The results of this trial show equivalence of both medications in the treatment of recurrent herpes orofacialis, and confirm the good dermal tolerability of the drugs. PMID- 8494584 TI - [Family physicians in sparsely populated regions must spread out their practice territory]. PMID- 8494583 TI - Biological activity of bacterial cell wall components. Immunogenicity of an immunostimulating bacterial extract. AB - An immunostimulating bacterial extract (IBE, Broncho-Vaxom) used for the prevention and treatment of recurrent respiratory tract infections consists of lyophilized fractions derived from 21 bacterial strains occurring in these infections. The immunogenic properties of IBE were determined in vivo in a murine model. It could be demonstrated that the extract constitutes an active immunogen in Balb/c mice. As shown by ELISA, IBE-specific antisera could be obtained after repeated i.p. immunizations; the antibodies were mainly of the IgG and IgM isotypes. The antibodies also bound - to a variable degree - to the bacterial strains used for the preparation of the extract. Additionally the antisera were shown to recognize the bacterial cell wall components porin, lipoprotein/lipopeptide and murein. Thus, IBE constitutes an active immunogen in vivo inducing antibodies directed against bacterial cell wall components; this could be of importance for understanding the therapeutic effect of the extract. PMID- 8494585 TI - Primary care: concern and debate. PMID- 8494586 TI - The myth of the abortion trauma syndrome revisited. PMID- 8494587 TI - [Ambulatory surgery--positive and negative aspects from the viewpoint of the established ENT physician]. AB - Operations on an outpatient basis have a long tradition in the ENT specialty and have been promoted in the Federal Republic of Germany. New legislation has now been passed opening up new perspectives but at the same time creating uncertainty. Organisation, medical and cost reducing advantages as well as various problems of the use of ENT operations on an outpatient basis are described from the view of a physician in private practice. Economic calculation is at present difficult to estimate. PMID- 8494588 TI - [Hyperplastic adenoids and growth of the facial skeleton]. AB - A case of a 16-year old female patient with large hyperplastic adenoids is presented. The only subjective symptoms were blocked nasal ventilation and subsequent permanent mouth breathing for 10 years. Concomitant sinusitis and middle ear affection were absent. In addition a gothic palate with malocclusion due to prognathism was found. The possible relationship between hyperplastic adenoids, chronic mouth breathing and craniofacial growth is discussed. PMID- 8494589 TI - [Manifestation of malignant lymphomatous polyposis of the nasopharynx]. AB - A 66 year old male patient with malignant lymphomatous polyposis of the gastrointestinal tract showed a manifestation in the nasopharynx. After 6 cycles of chemotherapy according to the CHOP-Scheme complete remission could be observed. 9 months after therapy no signs of recurrence were evident. PMID- 8494590 TI - [Color duplex ultrasound measurement of lymph node perfusion: a contribution to diagnosis of cervical metastasis]. AB - The objective of this study was to find additional sonomorphological criteria for determining the status of enlarged lymph nodes. By using colour-coded duplex sonography the perfusion of 63 lymph nodes in the neck was analysed. The status was confirmed either histologically or clinically (29 metastases from squamous cell carcinomas and 34 acute or chronic inflammatory nodal diseases). A quantitative evaluation of the pulsatility measured in 51 lymph nodes by computing the Pourcelot-Ratio and the Mean Pulsatility Index yielded significant differences between the two groups. By definition of a limiting value of the Pourcelot-Ratio (0.75) for the prediction of benignity, the specificity and the accuracy in screening for metastases were improved as compared to clinical examination and B-mode sonography. Additional criteria of dignity were found by qualitative evaluation of nodal perfusion patterns (presence and distribution of perfusion, partial loss of perfusion). The use of colour-coded duplex sonography in nodal disease of the neck provides an improvement of early and noninvasive diagnosis of regional metastatic involvement. PMID- 8494591 TI - [Electrophysiologic studies of the pattern of lesions of mimetic muscles in Bell's palsy]. AB - This paper reports on 379 investigations of patients with the diagnosis of Bell's palsy. The computerized analysis was carried out retrospectively with the programme FANDOS (6). In most electrophysiological measurements five standard muscles (frontalis muscle, orbicularis oculi muscle, levator labii muscle, zygomaticus muscle, orbicularis oris muscle) were investigated with electromyography (EMG); further, neuromyography was performed. In 77.3% of the cases electromyographically incomplete and 22.7% complete palsies were found. The distribution of the reduced innervation patterns and the degeneration of the muscles did not show a preferred lesion of certain muscles. In about sixty per cent of all cases in at least four muscles a homogeneous electromyographic pattern of the lesion in the mimic musculature could be detected. Degeneration potentials, however, were mostly found in one muscle only. In order to provide a differentiated analysis of the electromyographical state of a facial paresis an "EMG-index" was introduced that allows a general judgement of the "degree of palsy" in all five investigated muscles. An analysis of the time dependence of the "EMG-index" over the course of two weeks following onset of the palsy showed no variation during this time period. This proves that the complete status of the palsy is reached early after onset and that a deterioration or improvement is rarely seen within this time interval. PMID- 8494592 TI - [Facial paralysis in benign parotid tumor: case report and review of the literature]. AB - Generally, typical symptoms are significant for malignant parotid tumours: The infiltration of surrounding structures and facial paralysis. A case is reported where a benign parotid tumour (lymphadenitis) caused facial paralysis. Parotidectomy and the removal of the lymph node near the stylomastoid foramen led to complete restitution. A review of the literature of the past 40 years mentions 16 cases of benign neoplasms of the parotid gland that caused facial paralysis, such as pleomorphic adenoma, Warthin's tumour, oncocytoma, benign parotid cysts, chronic parotitis, lymphadenitis and parotid abscess. PMID- 8494593 TI - [Safe and rapid adenectomy]. PMID- 8494594 TI - [Treatment of "suppurating ear" with intact middle ear tubes]. PMID- 8494595 TI - Synthesis and DNA binding selectivity of pyrrole-amidine oligopeptides. AB - A class of DNA binding antibiotics endowed with antiviral and antitumor properties is reviewed. Starting from the original natural products, namely distamycin and netropsin, new compounds have been recently synthesized with the aim to obtain agents with specific affinity for defined DNA sequences and with different interaction mechanism (reversible or irreversible). PMID- 8494596 TI - Heterocyclic modulators of the NMDA receptor. AB - The design of new heterocyclic derivatives as modulatory agents at EAA receptors is described. In particular, the potent and selective activity at the NMDA receptor of trans-4-hydroxypipecolic acid-4-sulfate, as well as the neuroprotective properties of substituted thiokynurenates, a new class of competitive antagonists at the glycine site of the NMDA receptor complex, are reported. PMID- 8494597 TI - 3-Triazenopyrroles: synthesis and antineoplastic activity. AB - Some 3-triazenopyrroles were prepared by coupling 3-diazopyrroles and secondary amines. In preliminary in vitro screening tests derivatives 3 showed to be cytotoxic and exhibited mutagenic effects. PMID- 8494598 TI - Aminopyridazines--an alternative route to potent muscarinic agonists with no cholinergic syndrome. AB - In the search for central cholinergic agents which do not derive from already well-known agonists such as arecoline, pilocarpine or oxotremorine, we selected minaprine [3-(beta-morpholinoethylamino)-4-methyl-6-phenyl-pyridazine dihydrochloride] as a lead structure. Effectively, beside its antidepressive properties, minaprine shows a weak but highly selective affinity for hippocampic M1 receptors (IC50 = 17.10(-6) [3H]-pirenzepine). On the other hand minaprine has an excellent bioavailability and is well tolerated in human; particularly, minaprine does not induce any cholinergic syndrome. The synthesis of about 300 minaprine analogues was then undertaken using information resulting from a computer graphics analysis of published muscarinic ligands as well as classical structure-activity relationship considerations. These studies identified the features which are associated with high affinity for the muscarinic M1 receptors and led to the synthesis of ligands 5660 times more potent than minaprine. Taking into account factors such as the absence of a chiral center, the duration of activity, the metabolic stability led us to select compound SR 46559 A [3-(N-(2 diethylamino-2-methylpropyl)-6-phenyl-5-propylpyridazinamine sesquifumarate] for the industrial development. This compound is a potent orally active muscarinic agent, with no cholinergic symptom. PMID- 8494599 TI - Benzothiazine and benzothiazepine derivatives: synthesis and preliminary biological evaluation. AB - Several tricyclic benzothiazines and benzothiazepines have been synthesized by different intramolecular cyclization reactions. Their functionalization led to biologically active compounds. Some stereochemical aspects as well as biological responses have been outlined. PMID- 8494600 TI - Structure-based drug design: inhibitors of purine nucleoside phosphorylase. AB - The three-dimensional structure of the salvage pathway enzyme purine nucleoside phosphorylase (EC 2.4.2.1) as determined by X-ray crystallography has been used to design inhibitors of the enzyme. The design process is an iterative one utilizing X-ray crystallographic analysis, interactive computer graphics, Monte Carlo-based conformational searching, and energy minimization. The proposed compounds were synthesized, their IC50 values for inhibition of the enzyme determined, and the structures of their complexes with PNP analyzed by X-ray analysis. This procedure has led to the discovery of the most potent membrane permeable competitive inhibitors of this enzyme thus far reported. PMID- 8494601 TI - Distribution of pheophorbide A in normal tissues and in an experimental pancreatic cancer in rats. AB - The in vivo administration and distribution of a potent new photosensitizer, pheophorbide A (PH-A), was investigated in rats. The spectral characteristics were determined. This hydrophobic compound was solubilized by an ethanol/phosphate-buffered saline (PBS) mixture (v/v) and sonicated immediately before i.v. administration. Tissue distribution and the affinity of PH-A for an acinar pancreatic tumor were determined in Lewis rats for up to 48 h after a single i.v. administration of 3 mg kg-1 body wt. Methanol-extracted PH-A was quantitatively determined by fluorescence spectrophotometry at 665.6 nm. The PH-A uptake pattern showed that the reticulo-endothelial system is the major target of PH-A, followed by the gut and then the lung and pancreas. PH-A concentrations in skin were very low. The presence of an enterohepatic cycle was suggested by the PH-A biliary output, intestinal uptake and blood concentrations. Tumor PH-A retention was longer than pancreatic retention. The ratio of tumoral to peri tumoral pancreas PH-A was 6.7:1, 24 h after i.v. administration. With its similar tissue pattern, better absorption spectrum and lower skin toxicity, PH-A could be a more potent photosensitizer than hematoporphyrin derivatives. PMID- 8494602 TI - Nucleoside analogues. 13. The effect on anti-tumour activity of varying the uracil 5-substituent and the point of attachment (N1 or N3) of the uracil moiety in seco-nucleoside nitrosoureas. AB - The high activity against colon tumours in the mouse of nitrosoureas linked to seco-nucleosides with 5-fluorouracil or uracil as base component led us to synthesize and test similar drugs carrying other 5-substituted uracils attached by either N1 or N3. Not only were some of the new drugs active against the solid MAC 13 and against mammary and lung tumours, but unlike earlier compounds were particularly effective (especially N3 and alkoxy drugs like B.4083) against the ascitic MAC 15A, causing some cures. Further, these agents are valuable tools in the study, using modern techniques, of bifunctional alkylation of biological macromolecules, a vital principle of experimental cancer chemotherapy about which our knowledge is still very incomplete. PMID- 8494603 TI - Photosensitization with anticancer agents. 18. Perylenequinonoid pigments as potential photodynamic therapeutic agents: preparation and photodynamic properties of amino-substituted hypocrellin derivatives. AB - Perylenequinonoid pigments have demonstrated several photodynamic therapeutic advantages over the commonly used hematoporphyrin derivatives. Certain new amino substituted hypocrellin B derivatives have been prepared, and both direct and reductive aminations of hypocrellin B are described. The photophysical and photochemical properties of the amino-substituted hypocrellin B derivatives were investigated, and their significantly enhanced red absorptivities and strong 1O2 generating functions qualify them as promising photodynamic therapeutic agents. In addition, the superoxide anion radical was also determined to be implicated in the photosensitization of the amino-substituted hypocrellin B derivatives. PMID- 8494604 TI - Binding to DNA, cellular uptake and biological activity of a distamycin ellipticine hybrid molecule. AB - A hybrid molecule which conjugates the minor groove binding agent distamycin and an ellipticine derivative was synthesized and evaluated for cytostatic and cytotoxic activities against L1210 leukaemia cells in vitro. The binding of the hybrid molecule, named 'Distel', to a range of natural DNAs and synthetic polynucleotides with different base pair arrangements was studied by electric linear dichroism. The interaction with DNA simultaneously implicates binding of the distamycin part in the minor groove and intercalation of the ellipticine chromophore. The drug binds to DNA without any apparent preference for AT or GC polynucleotides, and can accommodate both homopolymeric and co-polymeric sequences as a binding site. However, the geometry of the drug-DNA complex varies depending on the targeted sequence. The lower activity of the hybrid as compared to the ellipticine derivative cannot be explained in terms of DNA binding. Taking advantage of the fluorescence of the pyridocarbazole chromophore, fluorescence microscopy was used to map cellular uptake of the hybrid molecule compared to the ellipticine derivative. Both the conjugate and the ellipticine derivative preferentially accumulate in the nuclei of HeLa cells rather than in the cytoplasm. Nuclei of ellipticine derivative-treated cells appear markedly more fluorescent than those of cells treated with the hybrid, which seems to be preferentially located in the nucleoli. Therefore, we consider the possibility that the difference in cytotoxicity between the two ellipticine-containing drugs is due to different intranuclear concentrations of these two compounds. PMID- 8494605 TI - Possible antineoplastic agents: Part XIII. Synthesis, biological evaluation and QSAR studies of some 1-(substituted benzenesulphonyl)-5-oxopyrrolidine-2 carboxylic acid derivatives. AB - Twelve analogues of 1-(substituted benzenesulphonyl)-5-oxopyrrolidine-2- carboxylic acid have been synthesized and tested for antineoplastic activity in Swiss albino mice with an Ehrlich ascites carcinoma (EAC) cell line. The values of percent inhibition of growth, both in ascitic cell count and fluid weight, have been taken as activity parameters. Quantitative structure-activity relationships (QSAR) have been studied using the LFER model. The best correlation (R2 = 93.0%) was found using molar refractivity (MR), which measures the molar volume and polarizability of the substituents. PMID- 8494606 TI - Assessing hypertension control and management. Hypertension Management Audit Project: a WHO/WHL study. PMID- 8494607 TI - Glycosylation of active human renin is necessary for secretion: effect of targeted modifications of Asn-5 and Asn-75. AB - Renin is a mammalian aspartic protease that is rate-limiting in the renin angiotensin cascade. Preprorenin is the translational product of the human renin gene and is secreted as prorenin, an inactive zymogen, primarily from the juxtaglomerular cells of the kidney. It has previously been shown that the 46 amino-acid pro domain is not necessary for the secretion of fully active or mature renin from mammalian cells. Additionally, previous reports indicated that glycosylation of Asn-5 and Asn-75, the two potential sites of N-glycosylation in renin, is not necessary for the secretion of prorenin from mammalian cells. In the present study, the role of N-glycosylation in the secretion of mature renin was examined. Asn to Ser mutations at one or both of the glycosylation sites of mature renin were made and the expression of these constructs was examined in COS, CHO, and Sf9 insect cells. In the absence of the pro sequence, N glycoylation at Asn-75 was essential for the secretion of active renin protein from all three cell types. The mutation at Asn-75 caused a more dramatic reduction in renin secretion than the mutation at Asn-5. This is in contrast to results previously reported for prorenin. PMID- 8494608 TI - Characterization of the cathepsin B gene and multiple mRNAs in human tissues: evidence for alternative splicing of cathepsin B pre-mRNA. AB - We have cloned and characterized multiple messages for cathepsin B that differ in their 5' and 3' untranslated regions (UTRs) from human kidney and the hepatoma cell line HepG2. A comparison of these messages with the cloned human cathepsin B gene reveals that they arise by alternative splicing of a single gene. Processing at a cryptic intron donor site in exon 11 and splicing to exon 12 produces a 4.0 kb message with an alternate 3' UTR in addition to the 2.3-kb message described previously by Chan et al. (1986). Variable removal of exon 2 produces cathepsin B mRNAs which differ by 88 nucleotides in their 5'-UTRs. The ratio of the 2.3-kb to 4.0-kb transcript is about 2:1 in most of the tissues examined, but the ratio of mRNAs with variant 5' UTRs differs widely. Cathepsin B mRNAs lacking exon 2 are predominant in human tumors. In addition, human breast and colon carcinomas and a human melanoma contain a cathepsin B transcript that is also missing exon 3 encoding the signal peptide and 7 residues of the activation propeptide. An in vitro transcription/translation assay was used to demonstrate that this message could be translated from an internal methionine codon (residue 52), producing a 32-kD product lacking the signal peptide and more than half the propeptide. The transcription/translation assay also demonstrated that the variant messages differ in their rates of translation. The relative rates are about 8:2:1 for mRNA lacking exons 2 and 3 compared to mRNA lacking exon 2 and mRNA containing the full-length 5' end, respectively. These results suggest that the expression of cathepsin B in human tissues may be regulated in part at the level of mRNA processing. PMID- 8494609 TI - Cloning and nucleotide sequence of a complementary DNA encoding Xenopus laevis metallothionein: mRNA accumulation in response to heavy metals. AB - A cDNA encoding Xenopus laevis metallothionein (MT) was cloned from a cDNA library constructed using liver poly(A+)RNA of X. laevis adult males treated with CdCl2. The probe used to screen the library was a MT-specific DNA fragment obtained by means of the polymerase chain reaction (PCR) and degenerate oligodeoxynucleotide primers. The cDNA clone encodes a putative protein of 62 amino acids, of which 20 are cysteine residues. The position of all the cysteine residues is conserved with respect to mammalian MT sequences. The amino acid sequence of this X. laevis MT, designated XIMT-A, shares between 60% and 67% identity with various vertebrate MTs. Overall, the structure of XIMT-A is no similar in sequence to MT-1 than it is to MT-2 isoforms of various vertebrates. Ten different X. laevis MT cDNA isolates were partially sequenced and turned out to be identical, suggesting a single species of MT mRNA. Southern blot analysis of X. laevis DNA reveals that the XlMT-A gene is present in at least two copies. This result is consistent with the suggestion that a genome duplication occurred in a X. laevis ancestor. The in vivo response to increasing doses of Cd2+, Zn2+, and Cu2+ metal salts was tested. In the liver, all three metals proved to be potent inducers, raising MT mRNA levels between 50- and 100-fold. The maximum response to Cd2+ was at 12 hr after injection and to Zn2+ at 24 hr after injection. High levels of mRNA were maintained for more than 48 hr. Cd2+ and Zn2+ induced XlMT-A mRNA in all tissues examined (kidney, spleen, heart, intestine, testes, and brain). Dexamethasone did not induce MT mRNA synthesis in the liver. PMID- 8494610 TI - Molecular cloning and expression of a metallothionein mRNA in Xenopus laevis. AB - Metallothioneins (MT) are expressed during early development in species of several groups. To understand MT function in developmental processes, we studied the MT system of Xenopus laevis, a model vertebrate species in experimental embryology. We first purified and sequenced the liver MT from copper-treated animals. This 62-amino-acid protein shares the main structural properties of known vertebrate MT, and is more closely related to avian than to fish or mammalian MT. Using this sequence, we designed oligonucleotide primers to amplify and isolate a MT clone from a XL2 cell line cDNA library. This 752-bp cDNA encodes a putative 62-amino-acid-long protein that is 100% identical with the sequenced MT. Zinc, cadmium, and copper ions are very efficient inducers of MT mRNA accumulation in Xenopus liver and cell lines. PMID- 8494611 TI - Molecular analysis of the Actinobacillus pleuropneumoniae RTX toxin-III gene cluster. AB - Actinobacillus pleuropneumonia strains that secrete three different exotoxins (ApxI, ApxII, and ApxIII) have been implicated in the etiology of porcine pleuropneumonia. To understand the role of these toxins in the pathogenesis of this disease, we have previously reported the cloning of the hemolysin gene (apxII) (Chang et al., 1989a), which encodes a 110-kD polypeptide with hemolytic and cytotoxic activity. To clone the third toxin gene (apxIII), a new genomic library using A. pleuropneumoniae serotype 2 chromosomal DNA was constructed. A series of five overlapping recombinant phage clones carrying the gene (apxIII) for this 120-kD antigen were identified using a DNA probe containing sequences from the Pasteurella haemolytica lktBD genes. Sequence analysis of a region of the cloned DNA reveals four open reading frames encoding proteins with predicted masses of 20.4, 112.5, 80.3, and 54.7 kD. These genes, designated apxIIC, apxIIIA, apxIIIB, and apxIIID, respectively, are similar in sequence to the RTX (repeat of toxin) toxin family. The toxin produced by the cloned gene kills BL-3 cells and is not hemolytic in vitro. PMID- 8494612 TI - Mutation analysis of Saccharomyces cerevisiae CDC6 promoter: defining its UAS domain and cell cycle regulating element. AB - Using beta-galactosidase as the reporter gene, we carried out mutagenesis experiments to investigate the 5' promoter region of the CDC6 gene. Our results showed that the DNA element, between -262 and -170, is important for the upstream activating sequence (UAS) activities. On the basis of the DNA sequence, there is a Mlu I (-204) and a Mlu I-like (-216) element located within the middle of the UAS region. Insertion and deletion mutagenesis analysis of the Mlu I sequence has indicated that the internal CGCG sequence of the Mlu I site (ACGCGT) is important for gene expression. Furthermore, when DNA elements containing the Mlu I sites were subcloned into the tester plasmid, periodic expression of a reporter gene throughout the cell cycle was observed, as evidenced by the beta-galactosidase activities and lacZ mRNA. Because the possible transcriptional initiation sites of the CDC6 transcript have been previously defined (Zhou and Jong, 1990, J. Biol. Chem. 264, 9022-9029), we propose a model regarding the construct of the CDC6 promoter region. This 5' promoter construct contains a UAS region and a Mlu I element (MCB box) typical of a family of cell cycle-regulated genes involved in DNA metabolism. Previous genetic studies have not completely defined the CDC6 execution point in the functional yeast cell cycle map. Our results favor the possibility that the CDC6 gene is required, and directly involved, in the initiation of DNA replication. PMID- 8494613 TI - Current modes of treatment of pituitary tumours. PMID- 8494614 TI - The far lateral approach for ventrally placed foramen magnum and upper cervical spine tumours. AB - Tumours of the foramen magnum region present a considerable surgical challenge. Their location combined with the close anatomical relation to sensitive and important vascular and nervous structures can make total removal difficult and sometimes impossible. Posterior and posteriolateral approaches, despite their simplicity, offer poor exposure and require retraction or rotation of the spinomedullary junction. Anteriolateral extrapharyngeal approaches are restrictive when a spacious superior exposure is necessary, while the vascular structures hidden by the tumours themselves appear only at the end of a rather tedious resection. The direct anterior transoral route, although effective for midline lesions, can be restrictive for laterally placed or broad-based tumours. A true lateral exposure provides an attractive alternative, the only anatomical obstacles being the horizontal part of the vertebral artery and the occipital condyle with its articulation with the lateral atlantal mass. A lateral approach was used in 15 patients with ventrally located tumours of the craniocervical junction, resulting in 12 total and three subtotal removals. In no case has there been inadequate tumour exposure and there were no complications of instability, CSF leak or infection directly related to the operation. Important advantages of the approach include: excellent exposure of the ventral spinomedullary junction, early and safe exposure of vascular structures, preservation of stability, minimal risk of infection, elimination of the need for neuraxis retraction and simplicity of instruments and technique. PMID- 8494615 TI - Post-traumatic chiasmatic disruption. AB - Ten patients with traumatic disruption of the optic chiasm are presented. The clinical sequence of fronto-facial trauma and CSF rhinorrhoea, followed days later by diabetes insipidus and discovery of a bi-temporal visual field loss constitute a characteristic syndrome which should be recognized by the attending medical staff. Magnetic resonance imaging, not previously reported, and post mortem evidence point to a physical disruption of the chiasm and infundibulum as the cause of the visual and hypothalamic signs. The resulting field defect is permanent but the diabetes insipidus is transient in 50% of patients and can be adequately managed with manipulation of the patient's fluid intake. PMID- 8494616 TI - Ischaemic deterioration following aneurysmal subarachnoid haemorrhage: definition by clinical criteria. AB - Ischaemia following surgery for aneurysmal subarachnoid haemorrhage (SAH) was defined by clinical criteria. Two distinct groups of patient developing ischaemia were identified: (1) patients recovering from anaesthesia with a new deficit or (2) patients developing 'true' delayed ischaemia. The only significant difference between the groups was an excess of pre-existing vascular disease in the former group. The eventual outcome for patients developing an immediate postoperative deficit was not significantly different from the delayed ischaemia group. The 6 month outcome for patients without clinical ischaemia in the first 10 postoperative days was excellent. The potentially different aetiology of ischaemia in the two subgroups with clinical ischaemia identified in this study should be considered during the planning and in particular the statistical design of trials testing new treatments for clinical ischaemia following aneurysmal SAH. PMID- 8494617 TI - The role of image-directed biopsy in the diagnosis and management of brainstem lesions. AB - The appreciation that brainstem tumours do not comprise a homogeneous pathological group and that up to 20% of the preoperative radiological diagnoses of brainstem lesions prove at operation to be wrong, has established the need for a firm histological diagnosis prior to treatment. Current neuro-imaging modalities may have increased the diagnostic accuracy and the detection rate of intrinsic brainstem lesions, but open exploration in cases without an exophytic component is still associated with a low diagnostic yield and considerable morbidity. A series of 72 brainstem lesions approached stereotactically with CT or MRI guidance is presented. A transcortical frontal precoronal trajectory was used in 58 and a suboccipital transcerebellar route in 14. Haematoma was diagnosed preoperatively in 16 cases and therapeutic aspiration was planned. In 56 cases the diagnosis was uncertain, although intrinsic tumour was suspected. A histological diagnosis was established in 52 cases, although in the remaining four cases a tumour was excluded. Unexpected findings occurred in over 15% of the cases. There were no operative deaths and the morbidity was low. In no case was there a permanent neurological deterioration directly related to the procedure, although there was a transient deterioration in two patients and another patient required early re-aspiration of a haematoma. PMID- 8494618 TI - Prediction of recurrence in pituitary tumours: a flow cytometric study using in vivo bromodeoxyuridine. AB - Although most pituitary tumours are regarded as benign, there is a significant risk of local recurrence and a few are frankly malignant. The prediction of clinically aggressive behaviour by histopathological means is inadequate and the selection of patients for postoperative radiotherapy has often been empirical. The flow cytometric analysis of the DNA content of certain intracranial tumours has suggested a correlation between a high proliferative index and a tendency to recur. The in vivo administration of bromodeoxyuridine (BUdR) yields a reliable and accurate S-phase labelling index and evaluation by flow cytometry allows a much greater and therefore more representative number of cells to be examined. We report our results for the flow cytometric evaluation of the S-phase fraction in a group of 11 human pituitary tumours following the preoperative administration of BUdR and discuss the correlation between high values of S-phase fraction and clinically aggressive behaviour. Initial results suggest a correlation between radiological evidence of tumour invasion and an S-phase greater than 2%. PMID- 8494619 TI - Wound closure after acoustic neuroma surgery. AB - Cerebrospinal fluid leakage from the wound or middle ear cavity remains a common cause of morbidity after acoustic neuroma surgery, regardless of the operative route employed. An incidence of around 15% is reported in most large series. The authors describe a method of wound closure which is applicable to both translabyrinthine and retrosigmoid tumour excision. Adoption of this technique in 188 consecutive patients has reduced the incidence of this complication in our unit from 13% to 1.6%. PMID- 8494620 TI - Racial differences between Maori and European New Zealanders in aneurysmal subarachnoid haemorrhage. AB - Racial differences in the incidence and rate of rupture of intracranial aneurysms are well recognized. A retrospective study of racial differences between Maori and European New Zealanders presenting to the Auckland Regional Neurosurgical Unit between 1985 and 1990 was conducted. It was found that the incidence per 100,000 of the population for all aneurysms was 14.3 for Europeans and 25.7 for Maoris. The mean age at rupture was 10 years earlier in Maoris with single aneurysms. A strong association between aneurysmal subarachnoid haemorrhage and cigarette smoking was found in both groups not only for single, but also for multiple aneurysms. Maoris were also found to have an abnormally high incidence of middle cerebral artery aneurysms and a low incidence of vertebrobasilar ones compared with Europeans. PMID- 8494621 TI - Myelography in the assessment of children with medulloblastoma. AB - Forty-seven out of 49 patients with a histologically-proven diagnosis of medulloblastoma admitted to our institution between 1 January 1984 and 13 December 1990 were examined post-operatively using either myelography or gadolinium-enhanced magnetic resonance imaging in an attempt to detect clinically occult spinal metastatic disease. Spinal spread of the tumour was identified in nine (19%) patients. Of the 16 patients for whom a 5-year follow-up has been available 12 had no myelographic evidence of spinal disease and of these 10 (83%) remain disease-free. Of the six who have died during this period four had evidence of spinal metastases at presentation. Of all the children in the series with spinal spread identified at the time of their initial hospitalization, only one survives to date (15 months after diagnosis). The remainder had an average life expectancy of 18 months. PMID- 8494622 TI - The anterior approach to high thoracic (T1-T2) disc herniation. AB - A patient with a T1-T2 disc herniation, operated on via the anterior approach, is presented. In a search of the literature we found 18 reported cases, all operated on by posterior or posterolateral approaches. The feasibility of the anterior discectomy in our case was established by preoperative magnetic resonance imaging of the upper thorax. We think that an anterior discectomy at the level of the upper thoracic spine can be easily performed in selected cases. The clinical picture of T1 root compression is described. PMID- 8494623 TI - Primary dorsal exophytic ependymoma. PMID- 8494624 TI - Successful conservative management of spontaneous spinal extradural haematoma. AB - A 69-year-old man developed severe neck and back pain with paraparesis which resolved within 2 h of onset. A CT myelogram demonstrated an extensive anterior extradural haematoma. This and several other cases from the literature suggest that patients with spontaneous spinal haematomas who rapidly recover from their neurological deficit do not require urgent surgical decompression. PMID- 8494625 TI - Schwannoma in the psoas muscle removed by the retroperitoneal approach. AB - The case of a 56-year-old male with a schwannoma in the right psoas muscle is reported. The tumour was extirpated by the retroperitoneal approach, which afforded direct access to this lumbar paraspinal lesion. PMID- 8494626 TI - Roentgen ray anomalies. Bilateral, retained deciduous molars. PMID- 8494627 TI - Mandibular Periapical Radiopacity. PMID- 8494628 TI - A possible instance of hypersensitivity to mercury after dental amalgam placement -a case report. PMID- 8494629 TI - Structure of 4-carboxy-2-nitrobenzeneboronic acid. AB - 4-(Dihydroxyboryl)-3-nitrobenzoic acid, C7H6BNO6, M(r) = 210.94, monoclinic, P2(1)/n, a = 10.542 (2), b = 6.411 (1), c = 13.105 (4) A, beta = 106.47 (2) degrees, V = 849.3 (4) A3, Z = 4, Dm = 1.65 (flotation in CCl4/1,2 dibromoethane), Dx = 1.649 Mg m-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.135 mm 1, F(000) = 432, T = 293 K, R = 0.0530 for 1328 observed reflections with F > 2 sigma(F). The molecule is flat [the carboxy and nitro groups are rotated 5.8 (4) and 1.9 (4) degrees, respectively, out of the plane] with the boronic acid group almost normal to the plane of the benzene ring, 92.4 (3) degrees. The B atom and one O atom of the nitro group are separated by only 2.457 (4) A implying an interaction that is consistent with observed chemical behavior. PMID- 8494630 TI - American Society of Hypertension 8th Scientific Meeting. May 19-22, 1993. Abstracts. PMID- 8494631 TI - Separate dental hygiene board not justified: could hurt continuity, quality of comprehensive dental services. PMID- 8494632 TI - Why get involved? Government affairs prime for dentists. PMID- 8494633 TI - Answers to your questions regarding OSHA regulations. PMID- 8494634 TI - Characteristics of early onset esotropia. AB - Some 115 patients with a reported onset of esotropia within the first six months of life were studied retrospectively to assess ocular findings and the evolution of any changes with time. All patients had been treated by one ophthalmologist and one orthoptist since 1972. Of the 115 patients, 27% had an accommodative element associated with the esotropia. Patients with an accommodative esotropia had higher levels of hypermetropia when compared to the non-accommodative group, but there were no other distinguishing characteristics. The groups exhibited a large variation in angle size, ranging from four to 45 degrees at the initial visit. The presence of fusion, amblyopia and the degree of hypermetropia had no significant effect on the course of the squint. Amblyopia was noted in 67% of cases and appeared to stabilise at a later-than-expected age, with 66% of patients with amblyopia stabilising between eight and 11 years. Surgical intervention had no effect on the incidence of amblyopia at the initial or final visits. PMID- 8494635 TI - The long-term results of surgical correction of childhood esotropia. AB - The results of surgical management by one ophthalmologist of 102 patients with congenital esotropia and 74 patients with acquired esotropia in childhood were analysed. The majority of patients had undergone a monocular recession-resection procedure, with 91% and 93% of patients showing a reduction in the angle, of more than five degrees, following surgery for congenital and acquired esotropia respectively. Unexpectedly, varying the amount of lateral rectus resection from 3 to 6 mm, when combined with a constant 5 mm medial rectus recession, did not produce significantly different amounts of change in the ocular alignment after surgery. Patients with congenital esotropia generally developed a stable postoperative angle later than patients with acquired esotropia. The degree of improvement of ocular alignment with surgery was independent of hypermetropia, presence of preoperative amblyopia or fusion. PMID- 8494636 TI - The aetiology of ocular toxoplasmosis in Melbourne. AB - The biological mothers of 23 patients presenting with acute chorioretinal toxoplasmosis had sera screened for the presence of antibodies to Toxoplasma gondii. Twenty-two of the mothers (96%) had positive serology and one (4%) had negative serology. This is consistent with the hypothesis that most cases of ocular toxoplasmosis are congenital in origin, but indicates that some cases are due to acquired toxoplasmosis. PMID- 8494637 TI - Screening for congenital colour vision defects. A comparison between the Ohkuma and Ishihara plates. AB - A prospective comparison between the Ohkuma and Ishihara pseudoisochromatic (PIC) plates was carried out in a group of 400 patients attending a general ophthalmology practice. The sensitivity of the Ohkuma test was compared to the Ishihara test, and the specificity of both was determined by reference to anomaloscopy as a gold standard. Both tests correctly identified the same group of 24 patients as having a red/green confusion axis, and the Ohkuma test was equally as sensitive as the Ishihara. The grading plates in both tests are unreliable, but the Ohkuma test is quicker, easier to administer, gives less ambiguous responses and has a clearer cut-off score for abnormality. On the basis of this experience the Ohkuma test is recommended as more appropriate for routine colour vision screening than either the 24 or 38 plate Ishihara tests. PMID- 8494638 TI - Radiation hazards during cobalt 60 plaque therapy for choroidal melanoma. AB - Prompted by the concerns of the staff and patients, radiation hazards from Cobalt 60 (Co 60) plaque therapy for choroidal melanoma were recently assessed when two patients were concurrently treated at Christchurch Hospital. The risks from radiation to the attending medical staff, nursing personnel from the operating theatre and ward, and the patients' visitors were investigated. The radiation dose for all staff and visitors involved with the two patients was found to be well below the recommended weekly limits set by the International Commission on Radiological Protection. Our department code of practice to minimise radiation hazard during plaque therapy has been revised. PMID- 8494639 TI - Demographic characteristics of ophthalmic outpatients at the Royal Victorian Eye and Ear Hospital. AB - To investigate demographic aspects of the access to services at the Royal Victorian Eye and Ear Hospital (RVEEH), routine registration records on outpatients were linked to the population of state health regions, the distribution of ophthalmologists and projected population growth. In the six month period September 1990 to March 1991, 19,339 persons came to the hospital (Emergency Department or Outpatients) at least once with an eye problem. Most (93%) lived in the Melbourne metropolitan area. The largest group (40%) came from Health Region 6, the Western Metropolitan region, which also has the lowest density of ophthalmologists in Victoria (1.6 per 100,000 total population, excluding ophthalmologists in the central business district of Melbourne). In the sample, 7243 patients (37%) were aged 65 years or older. Of these older patients, 75% had multiple visits to the hospital for a given illness, compared with 30% in younger patients (P < 0.01). By application of projected age-group growth rates in the Victorian population to the current profile of RVEEH outpatients, we forecast a 32% increase in the number of outpatients attending the hospital over the 15 years to 2006, 10% more than the projected population growth of 22% over this period. PMID- 8494640 TI - Anaerobic orbital abscess secondary to intraorbital wood. AB - A case of anaerobic orbital cellulitis secondary to intraorbital wood and an approach to management are presented. Retained foreign bodies should be suspected in all penetrating orbital injuries involving wood. Computed tomography (CT) should be performed to delineate the location and size of any foreign body and to determine damage to adjacent structures. Magnetic resonance imaging (MRI) is useful in certain circumstances. Orbital infection should be anticipated and broad-spectrum antibiotic cover (including anaerobes) provided. Surgical intervention should be undertaken to remove any retained foreign bodies to prevent vision-threatening complications. PMID- 8494641 TI - Internal ophthalmoplegia--a complication of ocular varicella. AB - We report a case of unilateral internal ophthalmoplegia associated with varicella zoster in a five-year-old boy. Pupillary dilatation and accommodative paralysis persist after three years. A brisk reaction to topical pilocarpine suggests a denervation. Bifocal spectacle correction has restored the visual acuity. PMID- 8494642 TI - Computer hardware and software to assist the visually impaired and blind. AB - Modern developments in computer hardware and software for the business world have been adapted to allow the partially sighted and blind to participate successfully in computer usage in education, employment and recreation. Adaptations such as the enlargement of the whole screen display, production of enlarged print and voice output of screen contents can assist the partially sighted. Conversion of computer screen information into speech or braille can be used in conjunction with sound boards and touch pads to allow the totally blind access to the exact spatial layout of screen contents. Optical character recognition devices whereby the printed page can be accessed by computer, and recent voice recognition techniques which allow a computer to interpret voiced commands, can also be used to assist the totally blind. Developments in these areas are discussed together with specific examples of equipment now available which make use of the various methods described. PMID- 8494643 TI - Environmental specification of neuronal connectivity. PMID- 8494644 TI - Defective glia in the Drosophila brain degeneration mutant drop-dead. AB - To understand better the cellular basis of late-onset neuronal degeneration, we have examined the brain of the drop-dead mutant of Drosophila. This mutant carries an X-chromosomal recessive mutation that causes severe behavioral defects and brain degeneration, manifested a few days after emergence of the adult. Analysis of genetically mosaic flies has indicated that the focus of the drop dead mutant phenotype is in the brain and that the gene product is non-cell autonomous. We examined the adult drop-dead mutant brain prior to onset of symptoms and found that many glial cells have stunted processes, whereas neuronal morphology is essentially normal. Adult mutant glial cells resemble immature glia found at an earlier stage of normal brain development. These observations suggest that defective glia in the drop-dead brain may disrupt adult nervous system function, contributing to progressive brain degeneration and death. The normal drop-dead gene product may prevent brain degeneration by providing a necessary glial function. PMID- 8494645 TI - Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene. AB - We have isolated a cDNA encoding a high affinity, Na+/Cl(-)-dependent glycine transporter, GLYT-2, which is distinct from another glycine transporter, GLYT-1. While the 3' sequences of these two cDNAs are identical, the 5' noncoding regions and the N-termini are completely different. GLYT-1 is found only in the white matter of the CNS, while GLYT-2 is found in the gray matter of the CNS as well as in macrophages and mast cells in peripheral tissues. Our findings suggest that tissue-specific alternative splicing or alternative promoter usage from a single gene results in two mRNA products encoding similar but distinct glycine transporters. The anatomic distribution of GLYT-2 mRNA supports the emerging status of glycine as a supraspinal neurotransmitter and suggests that glycine may function as a chemical messenger outside the CNS. PMID- 8494646 TI - Lithium treatment blocks long-term synaptic depression in the striatum. AB - We have studied the effect of acute and chronic lithium treatment on the activity of striatal neurons recorded from corticostriatal slices. Under control conditions, tetanic stimulation of glutamatergic corticostriatal terminals caused long-term depression (LTD) of excitatory synaptic potentials. Acute lithium treatment did not affect the peak of the induction phase, but it reduced the following phases of LTD. LTD was completely blocked in slices obtained from rats chronically injected with LiCl. Lithium treatment failed to affect the intrinsic membrane properties of striatal neurons and the presynaptic inhibitory effects of carbachol and t-ACPD. We suggest that the lithium-induced blockade of LTD may contribute to the therapeutic action of lithium salts in mania and depression. PMID- 8494647 TI - Alternative forms of rat TrkC with different functional capabilities. AB - We have identified transcripts encoding several different forms of rat TrkC, a member of the Trk family of receptor tyrosine kinases that serves as a receptor for neurotrophin-3. Some forms of TrkC lack the intracytoplasmic kinase domain and thus resemble previously defined truncated variants of TrkB. Other forms of TrkC contain variable-sized amino acid insertions within the tyrosine kinase domain. Transcripts encoding all forms of TrkC can be detected throughout the nervous system, displaying substantial overlap as well as mutually exclusive distribution patterns with transcripts for TrkB. Strikingly, only transcripts encoding the truncated forms of TrkB and TrkC are found in astrocytes, peripheral nerve, and nonneural tissues. Finally, forms of TrkC containing insertions within the kinase domain retain their ability to autophosphorylate in response to neurotrophin-3, but cannot mediate proliferation in fibroblasts or neuronal differentiation in PC12 cells. PMID- 8494648 TI - The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. AB - Members of the Trk tyrosine kinase family have recently been identified as functional receptors of the NGF family of neurotrophins. Here we show the rat trkC locus to be complex, encoding at least four distinct polypeptides. Three of the encoded polypeptides are full-length receptor tyrosine kinases that differ by novel amino acid insertions in the kinase domain. A fourth protein is a truncated receptor that lacks the catalytic domain. Tyrosine phosphorylation, cross linking, and ligand binding assays indicate that TrkC receptors interact with NT 3 and not with the related neurotrophins NGF, BDNF, xNT-4, or hNT-5. Furthermore, high and low affinity NT-3-binding sites are associated with the TrkC receptors. Stable and transient expression of TrkC receptors in PC12 cells indicates that the neurite outgrowth response elicited by NT-3 is dramatic in receptors lacking the novel kinase insert (gp150trkC) but absent in receptors containing the 14 amino acid insert in the kinase domain (gp150trkC14). These data suggest that the trkC locus encodes receptors that may be capable of mediating different biological responses within the cell. This could have important implications in understanding the role of neurotrophins in the development of the vertebrate nervous system. PMID- 8494649 TI - Microbial colonization of human tooth surfaces. PMID- 8494650 TI - [The effect of a new formulation of almagate on gastroesophageal reflux in esophagitis patients. A randomized, single-blind and cross-over study]. AB - The effect of postprandial administration of a new formulation of almagate (1.5 g, po) or an association of alginate + antacid (2.4 g, po) on gastric alkalinization and gastroesophageal reflux were assessed in a randomized, single blind, cross-over study in 21 patients with gastroesophageal reflux disease. Continuous intragastric and esophageal acidity was evaluated by postprandial intraluminal pHmetry. When comparing both preparations, the new formulation of almagate significantly improved all pHmetric variables (number of reflux episodes (3 vs 6, p = 0.029), time of esophageal exposition to pH < 4.0 (1vs 9 minutes, p = 0.009), duration of longest reflux episode (1 vs 3 minutes, p = 0.036), reflux index (1 vs 2, p = 0.047), and intragastric time with pH greater than 4.0 (108 vs 46 minutes, p = 0.003). This results suggest that the new formulation of almagate could be effective in the treatment of gastroesophageal reflux disease, since acidity profile of patients treated with it have been shown an intragastric long lasting alkalinization wave. PMID- 8494651 TI - [Fecal excretion and the clearance of alpha 1-antitrypsin in patients with Crohn's disease]. AB - In previous work we defined the normal values of faecal alpha-1 antitrypsin (A1ATF) and their plasmatic clearance (CLAT) in 25 healthy patients. The aim of the present study is to compare these previous results with new results obtained when we applied this test to 30 patients with Crohn's disease (CD). We also show the good performance of the mentioned tests as indicators of the intestinal inflammatory activity. We compare the values of A1ATF and CLAT of healthy patients with those of CD patients. We also compare the Crohn's Disease Activity Index (CDAI) and Simple Index between active and inactive CD patients. Our results show significant differences between A1ATF excretion and CLAT as measured in healthy and CD patients. The relationship between those parameters could be explained by the equation CLAT = 0.325 x A1ATF. Active and inactive CD patients only differ significantly with respect to their leucocytes and C reactive protein values. In our group the A1ATF excretion is larger in CD patients with colonic disease. PMID- 8494652 TI - [The determination of tissue CEA in colorectal adenocarcinomas: an immunohistochemical study]. AB - We carried out a CEA immunohistochemical study on 80 colorectal carcinomas, using the PAP methodology. Also we studied peritumoral "normal" mucosa on 69 cases. All tumoral (80/80) and the major part of normal colonic mucosa (68/69) cases stained positively. We present our experience with this immunohistochemical staining using a qualitative semi-quantitative evaluation, as an easy and reliable procedure. This permits to obtain, by immunostaining, a better homogeneous group of tumours (Apical, Mixed and Cytoplasmic, or Weak and Strong), necessary to further correlation with various tumoral parameters. On the basis of this evaluation, we found: A staining of weak intensity (65/68) of Apical type (55/68) in the vast majority of the normal, peritumoral mucosa. In tumors we found a prevalence of strong intensity (67/80), in relation to its major content of CEA. With respect to the type of immunostaining, although Apical staining (32/80) exists the Cytoplasmic (34/80) is predominant together with the Mixed type (14/80). This is expression of the alterations in secretion and distribution of the tissue CEA. We analyze the difficulties of such classification caused by the tumoral heterogeneity and we include other data whose significance is not always clear. PMID- 8494653 TI - [A correlation between serum levels of preoperative CEA and CEA immunohistochemical staining in colorectal carcinoma]. AB - We analyzed the distribution of tissue CEA in 80 colorectal adenocarcinomas with the PAP immunohistochemical technique. We used a qualitative method with a double grading criterion--topography and intensity of staining--as well as a semiquantitative method in the immunostaining interpretation. We applied a pattern of immunostaining: apical, cytoplasmic or mixed, to each tumor. Likewise, we obtained the pre-operatory serum levels of CEA. The normal value in our laboratory is less than 10 ng/ml. We correlated the immunostaining pattern with the serum levels of CEA, obtaining a global statistical significant correlation (p < 0.01), as well as apical versus cytoplasmic correlation (p = 0,0,3). The apical staining pattern agreed with this CEA levels < 10 ng/ml, whereas the cytoplasmic staining was associated with high frequency with CEA levels > 10 ng/ml. In conclusion the immunohistochemical staining for tissular CEA permits to improve the prognostic efficiency of serum CEA levels. PMID- 8494654 TI - [The hepatotrophic action of cyclosporin A in a model of hepatic ischemia in the rat]. AB - Liver ischemia is a common surgical situation. In this study the effect of 15 minutes of warm ischemia on liver regeneration in the rat is assessed. From hepatocytic DNA content (cytophotometrically measured), the percentage of regenerating hepatocytes (PRH) and the regenerative gradient (RG) are calculated in normal livers and following different regenerative stimuli: partial hepatectomy (70%) and cyclosporine (20 mg/kg i.p.). In resting livers (both controls and CsA-treated) the PRH and the RG were not modified by ischemia. However, liver regeneration following partial hepatectomy was significantly decreased by ischemia. In the other hand, CsA has increased the PRH and the RG in the four situations analyzed: resting and regenerating liver, both normoperfused or following 15 minutes liver ischemia. It is concluded that the hepatotrophic effect of CsA is not nullified by warm liver ischemia. PMID- 8494655 TI - [Trans-Kehr postoperative cholangiography in upright and horizontal positions: the morphofunctional aspects of the biliary tract]. AB - To change from the lying position to the upright position, in patients without their gallbladder, causes: a) a rapid and partial emptying of the biliary ducts towards the duodenum by the amplification of the opening phasic waves activity of the sphincter of Oddi (S. O.); b) an important reduction caliber of the main biliary duct (M. B. D) and c) stability of the intraductal pressure with slight raising in upright position. These physiological concepts allow a better cholangiographic exploration by means of a drip of 60 to 70 drops per minute of diluted tri-iodic in: 1) Upright position, which gives a good image regarding the terminal choledochus; of the biliary duodenal flow, and of the reduction of the caliber of the MBD. 2) In lying down position which allows: the filling up of the complete biliary-tree with possible scarcity of information about the distal choledochus-duct; the appreciation of the degree of the expansion of the MBD, and the measuring of the delay of the emptying out of the X-ray-opaque substance in relation to what was found in the upright position. The elasticity of the walls of the biliary ducts acts efficiently in the compliance of the container and contained. In normal choledochal ducts, the top level images in the upright position do not go beyond the hepatic duct. When there are problems with the flow through the S. O., there is a filling up of the intrahepatic biliary ducts with the contrast substance introduced in the upright position. PMID- 8494656 TI - [Esophageal stenosis due to a dissecting intramural hematoma following the endoscopic sclerotherapy of esophageal varices]. AB - The dissecting intramural hematoma of the esophagus (DEH) is a rare complication of endoscopic variceal sclerotherapy (EVS). We present a 37 years male with Laennec's cirrhosis who developed a submucosal hematoma with complete obstruction of the esophagus 24 h. after the second session of EVS diagnosed by endoscopy. After conservative treatment the patient recovered well with complete resolution of the lesion. The review of the literature shows no correlation between DEH and type or volume of sclerosant, site of injection or previous number of sessions. Unknown in children. Most of these patients had abnormal hemostasis. We have performed EVS in 227 patients (879 sessions), with only a case of DEH (rate 0.13%). In this case the bad tolerance and movements during of EVS were very important. PMID- 8494657 TI - [Ganglioneuroma of the duodenum]. AB - Ganglioneuroma is an exceptional benign tumour of the duodenum and only three cases have been described previously. We report the case of a 71-year-old male in whom this pathology was incidentally discovered, as it usually happens with this type of tumour. Within rare duodenal nonepithelial tumours, gangliocytic paraganglioma is a fairly well defined entity characterized by a proliferation of neurons, Schwann cells, and endocrine-like epithelial cells. Ganglioneuroma lacks this last type of cells and represents and even rarer finding within tumoral pathology of the duodenum. The histopathogenesis of this tumor is discussed and there are theories that defend an hamartomatous origin against a neoplastic nature. PMID- 8494658 TI - [The echographic diagnosis of intestinal ischemia]. AB - A case of intestinal ischemia was identified using real-time ultrasound scanning on a forty-four-year old woman. This finding highlights the importance of ultrasonography in the emergency diagnosis of digestive diseases. PMID- 8494659 TI - [The brown bowel syndrome. A case report]. AB - We present a patient with celiac sprue in whom intestinal lymphoma was suspected. At laparotomy, a brown discolouration of small bowel loops was observed, and a transmural biopsy confirmed a brown bowel syndrome, an entity that is found in long-standing malabsorption conditions. We believe that the intestinal disorder caused by deposition of lipofuscin in the bowel non-striated muscle may cause radiologic changes similar to those seen in intestinal lymphoma. PMID- 8494660 TI - [A ventriculoperitoneal shunt as a rare cause of ascites]. AB - We report the case of a 22-year-old man with a craniopharyngioma, who developed ascites following a ventriculoperitoneal shunt procedure for hydrocephalus. The ascites was resolved with diversion of the distal catheter into the right atrium. A ventriculoperitoneal shunt can cause ascites, even without neurological symptoms suggestive of shunt malfunction. PMID- 8494661 TI - [Spontaneous paracentesis in cirrhotic patients with an umbilical hernia]. PMID- 8494662 TI - [Endoscopy and echography in a case of Schonlein-Henoch purpura with gastroduodenal involvement]. PMID- 8494663 TI - [The endoscopic treatment of a gastric submucosal lesion]. PMID- 8494664 TI - [Secondary actinomycosis of the abdominal wall simulating a neoplasm]. PMID- 8494665 TI - A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infection. AB - A comparative double blind trial was undertaken of the efficacy of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar abscesses. Patients were admitted to the trial with acute dentoalveolar abscesses with systemic involvement and assessments were made of pain, swelling, temperature and lymphadenopathy. After admission to the trial appropriate surgical therapy was undertaken. The patients were then given either phenoxymethylpenicillin 250 mg four times daily, cephradine 500 mg twice daily or amoxycillin 250 mg three times daily, all for 5 days. The patients were assessed after 2 days and 5 days. All the patients recovered with those taking cephradine showing the best recovery in the first two days of treatment. PMID- 8494666 TI - Visual and radiographic diagnosis of occlusal caries in first permanent molars and in second primary molars. AB - Diagnosis of early occlusal caries has proved more difficult than that affecting smooth or approximal surfaces. With time, this type of lesion has come to form a greater proportion of caries as a whole and its accurate diagnosis is consequently becoming more important. The most widely used methods of diagnosis are visual inspection and bitewing radiography but the value of both of these for occlusal caries has been questioned. The aim of this study was to investigate the validity of diagnosis using each of these two methods in extracted teeth. A total of 100 first permanent molars and 100 second primary molars were used and teeth and sites with questionable or borderline caries were selected for examination. The condition of the tooth on section was used to validate. In these samples sensitivity of radiographic diagnosis was greater than that of visual diagnosis. Both methods showed good specificity. When radiographs were used together with visual examination the status of 82% of first permanent molars and 91% of second primary molars were correctly classified. PMID- 8494667 TI - Perception of risk of HIV infection from regular attenders to an industrial dental service. AB - The advent of the HIV pandemic has necessitated the introduction of consistent cross-infection procedures for dentistry. Suprisingly little is known of patient reactions to some of these changes. A structured questionnaire was administered (in 1988/9, n = 613) to regular-attending patients of an industrial dental service to assess their views towards cross-infection procedures. Approximately a third of the study sample believed that there was a slight risk or more of contracting HIV infection at the dentist. This risk perception attenuated with further visits to the dentist. Some patients (13%) claimed to be aware from the media of someone having been cross-infected with the HIV virus from a dental visit. The majority of patients prefer the dentist to adopt the barrier methods of mask and glove wearing. Over 60% of patients would like their dentist to wear a mask when in fact a mask had not been worn. Accuracy of recall by patients for mask wearing was only 70% and for glove wearing 88%. The possibility that drawing the patient's attention to cross-infection control may be reassuring for the patient was not supported with some evidence to suggest that in instances where the dentist provided treatment, the patient's perception of risk was increased. PMID- 8494669 TI - British Cardiac Society annual meeting. London, 18-21 May 1993. Abstracts. PMID- 8494668 TI - Is half the profession apathetic to further learning? AB - In terms of the facilities and courses provided for their continuing education, general dental practitioners have never had it so good. Local dental tutors, employing sophisticated methods of market research and course evaluation, are becoming more sensitive to dentists' educational needs. PMID- 8494670 TI - Cryoelectron microscopy of microtubules. PMID- 8494671 TI - Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high-voltage electron microscopic tomography and graphic image reconstruction. AB - To define the ultrastructural accommodation of mineral crystals by collagen fibrils and other organic matrix components during vertebrate calcification, electron microscopic 3-D reconstructions were generated from the normally mineralizing leg tendons from the domestic turkey, Meleagris gallopavo. Embedded specimens containing initial collagen mineralizing sites were cut into 0.5-micron thick sections and viewed and photographed at 1.0 MV in the Albany AEI-EM7 high voltage electron microscope. Tomographic 3-D reconstructions were computed from a 2 degree tilt series of micrographs taken over a minimum angular range of +/- 60 degrees. Reconstructions of longitudinal tendon profiles confirm the presence of irregularly shaped mineral platelets, whose crystallographic c-axes are oriented generally parallel to one another and directed along the collagen long axes. The reconstructions also corroborate observations of a variable crystal length (up to 170 nm measured along crystallographic c-axes), the presence of crystals initially in either the hole or overlap zones of collagen, and crystal growth in the c-axis direction beyond these zones into adjacent overlap and other hole regions. Tomography shows for the first time that crystal width varies (30-45 nm) but crystal thickness is uniform (approximately 4-6 nm at the resolution limit of tomography); more crystals are located in the collagen hole zones than in the overlap regions at the earliest stages of tendon mineralization; the crystallographic c-axes of the platelets lie within +/- 15-20 degrees of one another rather than being perfectly parallel; adjacent platelets are spatially separated by a minimum of 4.2 +/- 1.0 nm; crystals apparently fuse in coplanar alignment to form larger platelets; development of crystals in width occurs to dimensions beyond single collagen hole zones; and a thin envelope of organic origin may be present along or just beneath the surfaces of individual mineral platelets. Implicit in the results is that the formation of crystals occurs at different sites and times by independent nucleation events in local regions of collagen. These data provide the first direct visual evidence from 3-D imaging describing the size, shape, orientation, and growth of mineral crystals in association with collagen of a normally mineralizing vertebrate tissue. They support concepts that c-axial crystal growth is unhindered by collage hole zone dimensions, that crystals are organized in the tendon in a series of generally parallel platelets, and that crystal growth in width across collagen fibrils may follow channels or grooves formed by adjacent hole zones in register. PMID- 8494672 TI - High voltage cryomicroscopy of human blood platelets. AB - We have analyzed the ultrastructure of human blood platelets using ultrarapid freezing techniques followed by either freeze-substitution fixation or direct imaging of frozen hydrated specimens in a high voltage electron microscope. Freeze substitution preserved a regularity in the arrangement of microtubules when compared with chemically fixed specimens, as identified by a preferred center-to-center distance of 30 nm. Platelets imaged in the frozen hydrated state during different stages of adhesion and spreading were rich in cytoplasmic detail and revealed novel features not previously reported. Different granule populations were distinguished in the unstained samples, and the morphology of the cells was dramatically different from that of dried cells. Membrane channels formed as the cells spread, increasing in size and number as the number of granules in the cell decreased, suggesting a fusion of granule membranes with one another or an additional membrane system to release their contents. The data support the idea that direct cryoimaging is an optimum method for characterizing rapid structural changes of labile organelles in whole cells. PMID- 8494673 TI - Preliminary electron crystallographic analysis of ice-embedded tropomyosin crystals. AB - Electron images and diffraction patterns of ice-embedded tropomyosin crystalline sheets have been recorded at 100 and 400 kV. Optical diffractograms from the images indicated an elongated, centered unit cell with a = 799.2 +/- 10.6 A, b = 55.1 +/- 3.5 A. Evaluation of the phases in the computed Fourier transforms up to 7 A resolution revealed the presence of symmetry axes consistent with two dimensional space group cmm. Electron diffraction patterns show diffuse arcs and discrete sampling at a resolution of 5.1 A, arising from the alpha-helical coiled coil features of the molecule. These results demonstrate that tropomyosin thin sheets are highly ordered and suggest that retrieval of its high-resolution three dimensional structure may be feasible by electron crystallography. PMID- 8494674 TI - A rotational offset model for two-stranded F-actin. AB - We propose the following "rotational offset" model for two independent strands of F-actin to account for the observation that it is possible, at times, for the crossover repeat to either alternate between long and short periods or remain constant (Bremer et al., 1991. J. Cell Biol. 115, 689-703). Rotational offset is the manifestation of the angular component of "lateral slipping" between the two long-pitch, right-handed strands comprising the actin filament. The present model is based on the premise that the longitudinal bond connecting the subunits along a single long-pitch strand is substantially stronger than the diagonal bond that connects interstrand subunits. We pose that, over fairly long stretches, the backbones of the two right-handed strands are individually close to being ideal helices, and that it is possible for the backbone of one strand to "roll across" the other. The rotational offset angle (epsilon 0) is the amount that one helical strand is angularly displaced relative to the position that otherwise would allow the two strands to be described as an ideal single genetic helix. Such an independent movement of the two strands is shown to shift the monomers that are involved in crossover points and produce the different patterns in crossover periods which have been observed from electron micrographs analysis. We specifically demonstrate that for a constant nonzero rotational offset the length of the crossover periods alternates, whereas for a constant offset of zero the crossover period remains constant. We also show that changes in the rotational offset angle along the filament can account for variable (random) crossover periods. PMID- 8494675 TI - Visualization of a ternary complex of the Escherichia coli Phe-tRNA(Phe) and Tu.GTP from Thermus thermophilus by scanning transmission electron microscopy. AB - Scanning transmission electron microscopy (STEM) was used to visualize formation of a ternary complex between the T. thermophilus elongation factor (EF) Tu.GTP and the Escherichia coli Phe-tRNA(Phe) labeled with an undecagold (Au11) cluster at minor nucleotide 3-(3-amino-3-carboxypropyl) uridine at position 47. The ternary complex was further characterized by the molecular mass and radius of gyration calculated from the mass distribution within the individual particles. Under conditions used for STEM imaging, the ternary complex is formed between Au11-labeled Phe-tRNA(Phe) and Tu.GTP in a yield up to 25%. The stoichiometry of EF-Tu.GTP to aminoacyl-tRNA (aa-tRNA) in the EF-Tu.GTP.aa-tRNA complex is 1:1, in agreement with the established view of the protein biosynthesis mechanism. The ternary complex is also formed, although to a lower extent, with GTP analogues (GMPPCP and GMPPNP, respectively), but not with Tu.GDP and nonaminoacylated tRNA(Phe) with Tu.GTP. PMID- 8494676 TI - On the formation and crystallization of sickle hemoglobin macrofibers. AB - We have characterized new aspects of macrofiber structure and assembly which provide a mechanism for macrofiber formation from fibers. After the formation of fibers, HbS forms macrofibers by the association of small, organized bundles of partially fused fibers. These macrofibers consist of double strands, packed into antiparallel rows, and are identical to double strands found in crystalline HbS, except that the double strands in macrofibers are axially displaced from their crystalline position and are twisted about the particle axis, whereas in crystals they are linear. In lateral views, electron micrographs of macrofibers show prominent sets of "rows." We use the number of these rows to designate a particular type of macrofiber. In this study we present micrographs of macrofibers with 3 to 11 rows visible in lateral views. Such particles contain from 20 to 200 double strands. The pitch of a macrofiber is coupled to the number of rows in a manner so that the angle between the molecules in the outermost double strand is always 1.8 degrees. This observation has led us to propose that the factor limiting the extent of lateral growth of macrofibers is distortions in bonding between the hemoglobin molecules in the outermost double strands. Similar considerations have provided an explanation of the factors that limit the lateral growth of fibers. Finally, we propose a simple mechanism for the formation of macrofibers from fibers. This mechanism postulates that integral numbers of fibers form specific types of macrofibers and has the virtue of conserving the polarity of the fibers. PMID- 8494677 TI - Biochemical characterization of lactobacilli from dry fermented sausages. AB - The characterization of 254 strains of lactobacilli isolated from dry spontaneously fermented sausages from 15 different producers at two different stages of ripening time is reported. The species identified were Lactobacillus sake 55%, L. curvatus 26%, L. bavaricus 11% and L. plantarum 8%. The main criteria for the identification of isolates to species level were: production of lactic acid isomers, presence of mDpm acid in cell walls, deamination of arginine and fermentation of mannitol and melibiose. The composition of the populations of lactobacilli were the same for the two stages of ripening. The deamination of arginine was tested in aerobic and anaerobic cultures and in different media by checking the production of ammonia and detecting the production of citrulline. In 94% of strains tested both methods gave identical results. In two L. sake strains arginine catabolism was dependent on culture media; for two other L. sake strains the deamination of arginine only occurred when oxygen was scarce. PMID- 8494678 TI - Phylogenetic relationships among wine yeast strains based on electrophoretic whole-cell protein patterns. AB - In the present work, a phylogenetic study based on protein electrophoretic profiles of Saccharomyces strains isolated from different Spanish wine regions has been carried out. Qualitative differences between the protein electrophoregrams were found at inter- and intraspecific level, but not between electrophoregrams of strains isolated at the same ecosystem. The numerical analysis of these results allowed us to conclude that intraspecific relationships are determined by ecological factors, as well as human influences (dispersion and artificial selection). A correlation between ecological and/or geographical origin and the relationships among strains was observed. PMID- 8494679 TI - Antilisterial activity of pediocin AcH in model food systems in the presence of an emulsifier or encapsulated within liposomes. AB - The listericidal activity of pediocin AcH was evaluated in slurries (5, 10, or 25% in dH2O) of nonfat dry milk, butterfat, beef muscle tissue, or beef tallow. Slurries were inoculated with Listeria monocytogenes (2-strain mixture; 2.5 x 10(6) cfu/ml) and then with pediocin AcH (30,000 arbitrary units (AU) per ml of slurry). Although pediocin activity was reduced in slurries, sufficient pediocin remained to decrease the listeriae population. For all slurries tested, the greatest decrease in counts of Listeria (1.2-1.8 log10 cfu decrease) and decrease in pediocin activity (12-54% recovery of original activity) occurred within 1.5 min of addition of pediocin to slurries. Thereafter, counts of Listeria did not change appreciably, but pediocin activity continued to decrease in most treatments for up to 60 min. In general, greater activity was recovered from: (i) slurries of lower (5%) compared to higher (25%) concentrations of food; and (ii) dairy- compared to meat-based slurries. Next, pediocin AcH was encapsulated within phosphatidyl-choline-based liposomes before addition to slurries (10%), or was used unencapsulated in slurries (10%) containing the emulsifier Tween 80. Greater pediocin activity (29-62% increase; average over all concentrations) was recovered from slurries containing encapsulated compared to free pediocin AcH. Likewise, greater pediocin activity was recovered from slurries containing an emulsifier (4-90% increase; average over all concentrations) compared to otherwise similar slurries without Tween 80. The additional recovery of pediocin activity afforded by liposomes or Tween 80 underscores the potential for direct application of biopreservatives to provide another hurdle for L. monocytogenes in foods. PMID- 8494680 TI - Modelling bacterial growth of Listeria monocytogenes as a function of water activity, pH and temperature. AB - Temperature, pH and water activity are important factors controlling the microbiological safety of foods. To describe the growth rate of Listeria monocytogenes in relation to these factors, two equations have been developed. Both equations are based upon the Ratkowsky equation for temperature and growth rate. The first equation predicts growth rate at sub-optimal pH values, sub optimal temperatures and sub-optimal water activities, the second model predicts growth throughout the entire pH range. The first model may be used to predict growth rates between pH 4.6-6.7, temperature range 5-35 degrees C and a water activity range of 0.95-0.997. The second model is valid throughout the pH range of 4.6-7.4 and the same temperature and water activity range as the first model. PMID- 8494681 TI - Evaluation of the toxicity of Salmonella selective media for shortening the enrichment period. AB - Five Salmonella serotypes recovering from heat injury exhibited different kinetics of resuscitation and growth. Exponential growth was reached before full resuscitation. Fully resuscitated cells and uninjured cells at low cell densities exhibited sensitivity when transferred from non-selective media to selective media, Rappaport-Vassiliadis (RV) and tetrathionate-brilliant green (TBG). The minimum number of cells required to survive in RV and TBG was determined and ranged from 10(2) to 10(5) CFU depending on the serotype. Salmonella grown in RV produced cell populations which exhibited no sensitivity when transferred to fresh RV even at low cell densities. Thus, toxic selective media enriched a resistant population. Selenite cystine exhibited no toxicity to resuscitated or uninjured Salmonella. The significance of these findings was discussed for the purpose of shortening the Salmonella enrichment period. PMID- 8494682 TI - Characterization of Listeria strains isolated from soft cheese. AB - Three soft cheeses were exposed to quantitative analysis for listeria and found to contain a large number of listeria. Thirty-five of the listeria strains isolated from the three cheeses were characterized by use of biochemical tests, serotyping, phagetyping and DNA restriction enzyme analysis. Seven isolates were identified as Listeria innocua and 28 as Listeria monocytogenes. Two to four different clones of L. monocytogenes could be identified from each cheese. In contrast, only one clone could be detected among the L. innocua isolates. From an epidemiological point of view the findings of different clones of L. monocytogenes in the same cheese emphasize the need for typing several listeria isolates from one and the same food sample. It is concluded that the best overview of the population of the listeria strains is obtained after direct plating of the sample followed by enumeration, isolation and extensive typing. PMID- 8494683 TI - Comparison of two enrichment media and three selective media for isolation of salmonellae from fresh chicken carcass rinse fluids and sewer swabs. AB - Slamonella was detected in 214 (45%) of 477 chickens examined. For Salmonella positive samples of fresh chicken carcass rinse water a sensitivity of 96% and 29% respectively was demonstrated for Rappaport-Vassiliadis (RV) and Selenite broth. A similar superiority of RV was found for the sewer swab samples. Among the three selective agar media investigated a limited sensitivity (below 50%) was found making it imperative to use at least two media, one of which should be deoxycholate citrate agar. PMID- 8494684 TI - Mycoflora and toxigenic Aspergillus flavus in Spanish milks. AB - The isolation, enumeration and identification of moulds were carried out on 64 samples of raw milk and 33 of pasteurized milk. The genera most frequently isolated in the raw milk were: Geotrichum (76.5%), Fusarium (45.3%), and Aspergillus (31.2%). In pasteurized milk they were: Aspergillus (61.5%) followed by Fusarium and Penicillium (37.7% in both cases). A. flavus was found in 12 samples and 1 out of the strains examined produced aflatoxins in vitro. The effect of pasteurization of the milk on spores of A. parasiticus NRRL-2999 was examined. The presence of moulds in pasteurized milk seems to be explained by contamination during bottling. PMID- 8494685 TI - The need for process optimization of African fermented foods and beverages. AB - Many papers have been published on various aspects of African fermented foods and beverages. The emphasis has been on the microorganisms used, and the nutritional status of the products after fermentation. The preparation of these products is still a traditional family art and the fermentation process is by uncontrolled inoculation. This has led to variations in the quality and stability of the products. Research efforts in this field are still based on old recipes transmitted from generation to generation due to the fact that the consumers are not easily influenced by innovations, and the apparent lack of biotechnological background. This paper gives a brief account of the fermentation process of some of the fermented products to show the varied pattern of the microbiology. The unpredictability of the complex microflora implicated in the fermentations, and the lack of adequate knowledge of the associated microbes are discussed. The paper suggests a number of steps to be taken to optimize the fermentation process as a means of maintaining the peculiar characteristics of each product and establishment of small-scale industrial production. PMID- 8494686 TI - Five-tube most-probable-number method using the Fung-Yu tube for enumeration of Listeria monocytogenes in restructured meat products during refrigerated storage. AB - The survival of Listeria monocytogenes in cooked, chopped hams stored at 5 degrees C for 5 weeks was studied. Slices of chopped ham (25 g) were inoculated with a three-strain mixture of L. monocytogenes (LM 101M, LM 103M, and Scott A) at levels of < or = 350 cfu/25 g and packaged in Stomacher bags. Prior to inoculation, L. monocytogenes cells were subjected to either heat-injury (56 degrees C, 30 min) or freeze-injury (-18 degrees C, 14 days). The organisms were detected by a five-tube most-probable-number (MPN) technique using the motility enrichment Fung-Yu tube, and the direct plating method. After storage at 5 degrees C for 1 week, there was a one log10 reduction in counts. Thereafter, Listeria recovered and heat- and freeze-injured cells grew to 10(7) and 10(8) within 5 weeks, respectively. Similar results were obtained from both methods. However, direct plating could not recover L. monocytogenes at low levels (< or = 100/25 g), whereas MPN counts were obtained at these low levels. The pH (6.22 +/- 0.10) of the chopped hams remained constant throughout the study. These results indicated that low numbers of L. monocytogenes surviving sublethal heat- or freeze-injury could initiate growth after recovery in chopped hams. The five-tube MPN method using the Fung-Yu tube was effective in enumerating both low and high levels of L. monocytogenes in food. PMID- 8494687 TI - Microflora and acidification properties of yogurt and yogurt-related products fermented with commercially available starter cultures. AB - Yogurts and yogurt-related milk products were produced using 44 commercially available starter cultures from 8 suppliers. The yogurt starters consisted of the classical yogurt microflora and the yogurt-related cultures containing Lactobacillus acidophilus and/or Bifidobacterium spp. instead of or in addition to the yogurt bacteria. The counts of lactobacilli in the fresh yogurts varied between 5.5 x 10(7) and 6.5 x 10(8) CFU/ml, and the counts of streptococci varied from 3.5 x 10(7) to 1.2 x 10(9) CFU/ml. About 80% of the yogurts had higher counts of cocci than rods. During storage of the products for 2 weeks at 6 degrees C the stability of the microflora differed markedly among the cultures. In the fresh yogurt-related products the L. acidophilus counts ranged from 4.0 x 10(5) to 2.6 x 10(8) CFU/ml; bifidobacteria were found at levels between 4.0 x 10(6) and 2.6 x 10(8) CFU/ml. In most products reduced viable counts of these bacteria were observed after 2 weeks. Titratable acidity increased on average by 22.3% in the yogurts, and by 14.9% in the yogurt-related products during storage. In most products a higher amount of L(+)- than D(-)-lactic acid was found. PMID- 8494688 TI - Sugar uptake and involved enzymatic activities by yeasts and lactic acid bacteria: their relationship with breadmaking quality. AB - The uptake kinetics of sugars present in wheat doughs and alpha-glucosidase as well as beta-fructosidase activities were determined in different strains of yeasts and lactic acid bacteria. These strains were previously selected according to their breadmaking quality. Saccharomyces cerevisiae (P6), Candida guilliermondii (P40), Lactobacillus plantarum (B31 and La18) and L. brevis (B21) showed good performance, while Sacch. fructuum (P43), L. cellobiosus (B37) and Enterococcus faecium (B11) yielded bread of lower quality. Leuconostoc mesenteroides (B10), when used in combination with other strains led also to high quality starters. All yeast strains used assimilated glucose, fructose and maltose, exhibiting saturable kinetics. Lactic acid bacteria showed saturable kinetics only for hexoses, whereas disaccharide uptake was linear. Sacch. cerevisiae, Leuconostoc mesenteroides, L. brevis and L. plantarum (B31) displayed better sugar uptake properties. For all the strains used alpha-glucosidase and beta-fructosidase activities were detected. The highest specific activities were found for Sacch. cerevisiae, C. guilliermondii and L. plantarum (B31). These results indicate good correlation between the parameters evaluated and the breadmaking potential of the microorganisms. PMID- 8494689 TI - Construction and comparison of response surface kinetic models for the Yersinia enterocolitica type strain and a food isolate under aerobic conditions. AB - Response surface models were constructed for the type strain of Yersinia enterocolitica (ATCC 9610) and a wild type strain isolated from sliced roast lamb, for various conditions of temperature, pH, sodium chloride concentration and sodium nitrite concentration. Both strains grew at similar rates except at the 'extremes' of the conditions tested. Models for both quadratic and cubic polynomial equations are shown. The results obtained indicate that the cubic model is superior. PMID- 8494690 TI - Comparative evaluation of two methods of enumerating enterococci in foods: collaborative study. AB - Two methods of enumerating enterococci in foods were compared in a collaborative study. Thirteen laboratories tested four blind duplicate samples containing different levels of enterococci and two negative control samples. Freeze-dried mixtures of bacteria were used as simulated food samples. The freeze-dried samples were reconstituted and either spread directly on the surface of Slanetz and Bartley medium (SB) and incubated at 44 degrees C for 48 h or preincubated in tryptone soya agar at 37 degrees C for 2 h before being overlaid by SB and incubated at 37 degrees C for a further 46 h. The numbers CFU of enterococci recovered by the two methods were not significantly different except for one sample where the 37 degrees C method gave a somewhat higher recovery. The 44 degrees C method was less time-consuming and less laborious. PMID- 8494691 TI - Fate of Listeria monocytogenes in raw and cooked ground beef with meat processing additives. AB - The effect of sodium lactate (1.8% w/w), sodium erythorbate (0.1% w/w), kappa carrageenan (1% w/w), and the alginate meat binder (0.4% w/w, sodium alginate; 0.6% w/w lactic acid; and 0.075% w/w calcium carbonate) on Listeria monocytogenes survival and growth was determined in raw and cooked ground beef stored aerobically at 4 degrees C. There was no significant (P > 0.05) increase in numbers of L. monocytogenes during storage of raw ground beef. However, L. monocytogenes numbers were generally lower in treatments with sodium lactate, and higher in sodium erythorbate compared to controls and meat with other additives. Increases in total aerobic plate counts were less pronounced in raw meat formulated with sodium lactate and alginate meat binder than with other additives. Cooking meat with initial inoculum levels of 6.52 to 7.03 L. monocytogenes log CFU/g to 65 degrees C resulted in lower destruction (0.56 and 1.18 log CFU/g) in samples with added alginate meat binder and kappa-carrageenan, respectively, compared to the control. Survivors (2.11-3.73 log CFU/g) decreased initially and then increased slightly, but not significantly (P > 0.05), during storage (4 degrees C, 6 days) of the cooked products. PMID- 8494692 TI - Heavy metals as selective inhibitors of mould growth. AB - Ten heavy metals were tested in malt extract agar for their selective activity on nine food relevant fungi. The variations observed as growth inhibitory for heavy metals investigated indicated good possibility for designing selective media. PMID- 8494693 TI - Radiation-induced transient cisplatin resistance in murine fibrosarcoma cells associated with elevated metallothionein content. AB - Cisplatin resistant mouse fibrosarcoma cells were isolated after fractionated irradiation in the absence of any drug treatment. Several sublines have been established; clone SSK-rad1 was used for further studies. These cells exhibit unchanged radiosensitivity and are compared to cisplatin resistant sublines, SSK cis2, previously induced by low dose cisplatin exposure. Both resistant sublines are characterised by reduced CdCl2 sensitivity, indicating enhanced metallothionein content; loss of cisplatin resistance occurs after 10 to 25 generations and correlates with rising CdCl2 toxicity. Increase of MT is demonstrated directly by 109Cd binding to the MT containing region after FPLC. Both sublines differ in GSH level, which is increased only in SSK-rad1 cells, and in cellular platinum content, which is reduced in SSK-cis2 cells compared to the parental SSK cell line. These factors may contribute to cisplatin resistance but are not the main cause responsible for the transient nature of the drug resistance observed. Our results indicate that transient cisplatin resistance in SSK cells can be induced not only by the drug itself but also by gamma irradiation and is based on the same mechanism of increased cellular MT content. PMID- 8494694 TI - Inhibition by amiloride of gastric carcinogenesis induced by N-methyl-N'-nitro-N nitrosoguanidine in Wistar rats. AB - The effects of amiloride on the incidence and histological types of gastric cancers in Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index and proliferative fraction of gastric mucosa were investigated. After oral treatment with MNNG for 25 weeks, rats received s.c. injections of amiloride (0.25 mg kg-1 or 5.0 mg kg-1 body weight) in depot form every other day until the end of the experiment. Prolonged administration of 5.0 mg kg-1, but not 2.5 mg kg-1 of amiloride significantly decreased the incidence of gastric cancers in Week 52. However, it did not influence the histological features of the gastric cancers. It also significantly decreased the labelling index and proliferative fraction of the antral mucosa. These findings indicate that amiloride inhibits the development of gastric cancers, and that its effect may be related to its effect in decreasing cell proliferation of the antral mucosa. PMID- 8494695 TI - Opposing behavioural alterations in male and female transgenic TGF alpha mice: association with tumour susceptibility. AB - Psychosocial factors are thought to influence risk and survival from cancer. We have previously studied specific behaviours in transgenic male CD-1 MT42 mice, which overexpress the gene encoding human transforming growth factor alpha (TGF alpha) in multiple tissues, and which develop a high incidence of spontaneous hepatocellular carcinoma. The male TGF alpha mice spent a lengthened time immobile in the swim test, were highly aggressive, had increased plasma levels of 17 beta-estradiol (E2), and reduced natural killer (NK) cell activity. The female transgenic MT42 TGF alpha mice do not develop an increased rate of tumours at any site. We hypothesised that if the alterations in male TGF alpha mice are associated with their development of hepatocellular carcinomas, female TGF alpha should not show these alterations. The data in the present study indicate that female TGF alpha mice display shortened immobility in the swim test, suggesting an improved ability to cope with stress, and appear less aggressive in the resident-intruder test than non-transgenic female CD-1 mice. The female TGF alpha mice also exhibit a 3-fold increase in the plasma levels of E2, and a 3-fold increase in NK cell activity. These findings suggest that the elevated expression of TGF alpha in the transgenic mice is associated with gender-specific behavioural alterations, and the development of spontaneous hepatocellular tumours in the males. Furthermore, TGF alpha alters hormonal and immune parameters similarly in both sexes. It remains to be determined whether the development of hepatocarcinoma in the male TGF alpha animals is associated with an impaired ability to cope with stress and elevated aggressive tendencies and/or whether manipulations leading to an impaired ability to cope with stress will promote tumourigenesis in female TGF alpha mice. PMID- 8494696 TI - Comparability of surrogate and self-reported information on melanoma risk factors. AB - Surrogate reports by patients about their relatives, and vice versa, are potentially of great use in studies of the genetic and environmental causes of the familial aggregation of cancer. To assess the quality of such information in a family study of melanoma aetiology in Queensland, Australia, the authors compared surrogate reports with self-reports of standard melanoma risk factors obtained by mailed self-administered questionnaire. There was moderate agreement between surrogate reports provided by the cases and relatives' self-reports for questions on ability to tan (polychoric correlation coefficient (pc) = 0.60), skin colour (pc = 0.57), average propensity to burn (pc = 0.56), and hair colour at age 21 (kappa coefficient = 0.55), although relatives in the extreme risk factor categories were misclassified by surrogates at least half of the time. Agreement was lower for questions on degree of moliness (pc = 0.45), tendency to acute sunburn (pc = 0.42), and number of episodes of painful sunburn (pc = 0.23). The quality of relatives' surrogate reports about cases was similar to that of cases' surrogate reports about relatives. Cases who reported a family history of melanoma provided better surrogate information than did cases who indicated no family history, and female cases provided better surrogate reports than did males. Cases were better able to report for their parents and children than for their siblings. The authors conclude that when the use of surrogate reports of melanoma risk factors is unavoidable, results should be interpreted cautiously in the light of potentially high rates of misclassification. In particular, surrogate reports appear to be a comparatively poor measure of self-assessment of number of moles, the strongest known phenotypic indicator of melanoma risk, and may bias comparisons between families with and without a history of melanoma. PMID- 8494697 TI - The comprehensive assessment of health status in survivors of childhood cancer: application to high-risk acute lymphoblastic leukaemia. AB - The health status of 69 survivors of high-risk acute lymphoblastic leukaemia (ALL) is assessed using a multi-attribute classification system. Seven attributes are included: sensation, mobility, emotion, cognition, self-care, pain and fertility. Three to five levels of functioning are defined for each attribute. Comprehensive health states are described as a specific combination of seven attribute levels. The system captures combinations of sequelae. The system provides a compact but comprehensive tool for long term follow up of survivors of childhood cancer. The results underscore the cognitive and emotional burdens of morbidity affecting survivors of high-risk ALL. PMID- 8494698 TI - Melanocytic naevi and melanoma in survivors of childhood cancer. AB - There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood. PMID- 8494699 TI - The value of the human milk fat globule membrane antigen HMFG2 in epithelial ovarian cancer monitoring: comparison with CA125. AB - We assayed serum HMFG2 in serial samples from 215 primary epithelial ovarian cancer patients using an 'in-house' single determinant ELISA, 45% of patients with stage I, 54% with stage II, 61% with stage III and 75% with stage IV disease had elevated serum HMFG2. Post-operative levels were significantly related with residual tumour volume (P < 0.005), and fell in the majority of responders, although the association with response to first-line chemotherapy was not significant. HMFG2 had a sensitivity of 50% specificity of 83%, accuracy of 61%, PVP of 86% and PVN of 45% for disease at second-look laparotomy. Serial levels gave a lead time to clinical relapse in 47% of patients who responded to therapy, including one patient with negative CA125 levels. HMFG, paralleled CA125 in many respects, although it was elevated in fewer patients. In a stepwise discriminant analysis, HMFG2 added to the discrimination of CA125 (r = 0.183, P < 0.005), although additional accurate information was only given in patients with advanced poorly differentiated serous cystadenocarcinoma. Given that HMFG2 is expressed in few patients who are CA125 negative it is unlikely that it will have a significant clinical impact upon patient management. PMID- 8494700 TI - Squamous carcinoma of the head and neck: cured fraction and median survival time as functions of age, sex, histologic type, and node status. AB - The multivariate lognormal survival model can be used to determine the relationship of prognostic covariates to two important parameters of malignancy. Cured fraction and median survival time among uncured patients. Analysis with this model revealed that cured fraction is primarily a function of histologic type and node status, while median survival time is primarily a function of age and node status. Patient sex was also related to likelihood of cure, but this association was of marginal significance. The symmetric impact of node status on both cured fraction and median survival time is consistent with known biologic principles. The strongly asymmetric relationships of histologic grade to cured fraction and age to survival time suggest, however, that likelihood of cure and survival time may not operate by identical biologic mechanisms. PMID- 8494701 TI - Cathepsin D in breast secretions from women with breast cancer. AB - A proteinase accumulated in breast secretions from women with breast cancer has been characterised. Inhibition of the proteolytic activity of breast secretions by pepstatin A showed that the main enzyme involved was an aspartyl proteinase. Determination of its cleavage specificity by SDS-PAGE and amino acid sequence analysis revealed that it was identical to that of cathepsin D, an aspartyl proteinase suggested to be involved in breast cancer development. The identity between both proteins was further confirmed by immunological analysis with monoclonal antibodies against cathepsin D. Quantification of cathepsin D in nipple fluids from 41 women with benign or malignant breast diseases and from 19 control women without breast pathology revealed the presence of variable amounts of this proteinase. The average concentration of cathepsin D in breast secretions from cancer-bearing breasts was 7.2 +/- 2.2 fmol micrograms of protein, which was significantly higher than those of nipple fluids from control women (2.9 +/- 0.6 fmol micrograms-1) (P = 0.04) or from patients with benign breast diseases (2.1 +/- 0.3 fmol micrograms-1) (P = 0.004). Though the number of cancer patients studied was small (n = 21), no correlations were found with cytosolic concentrations of cathepsin D or oestrogen receptors, neither with other parameters such as tumour size, histological grade, axillary node involvement or menopausal status. PMID- 8494702 TI - Cervical intraepithelial neoplasia in patients with breast cancer: a cytological and colposcopic study. AB - Twenty-six patients with treated breast cancer who had been randomised previously to receive combination chemotherapy including alkylating agents (n = 14) or to undergo oophorectomy (n = 12) following surgery underwent cytological and colposcopic screening of the uterine cervix. Colposcopically directed cervical punch biopsies were taken from all patients in whom a colposcopic abnormality was detected. Breast cancer patients were compared with 79 controls with normal cervical cytology and no known breast malignancy. Colposcopically directed punch biopsies were taken from the cervical transformation zone of all controls. Significantly more breast cancer patients who had received chemotherapy (43%) than controls (10%) had CIN (P < 0.01) and significantly more patients who had received chemotherapy (14%) than controls (3%) had CIN 2 or 3 (P < 0.05). The proportion of breast cancer patients in the oophorectomy group with CIN (17%) did not differ significantly from the control group. No case of CIN was detected by cervical cytology. This study suggests that breast cancer patients receiving combination chemotherapy including alkylating agents are at increased risk of CIN, and that cervical cytology alone may be an inadequate form of screening for these patients. PMID- 8494703 TI - How fatal is breast cancer? A prospective study of breast carcinoma deaths in Tayside. AB - A prospective autopsy study of deaths of women who had been diagnosed previously as having cancer of the breast was performed between October 1986 and December 1990. During the study period 28 deaths occurred and nine of these (32%) were attributable directly to breast cancer; a figure similar to that found in our earlier retrospective study. In this study the autopsy findings in both the breast cancer and non-breast cancer deaths were recorded and five cases underwent post-mortem radiological skeletal survey to detect metastases. The findings confirm the role of the post mortem in modern medicine as a method of auditing clinical practice. Of particular importance, is the finding that the clinical presumption of disseminated breast cancer as a cause of 'terminal' illness in some patients may be misleading and dangerous, possibly denying some patients treatment of potentially remedial conditions by the institution of inappropriate terminal care. PMID- 8494704 TI - Mortality of a cohort of French uranium miners exposed to relatively low radon concentrations. AB - A cohort mortality study has been performed on French uranium miners having experienced more than 2 years of underground mining, with first radon exposure between 1946 and 1972. Vital status has been ascertained from the date of entry to the 31 December 1985 for 99% of the members of this cohort; causes of death are identified for 95.5% of the decedents. The different causes of death are compared to the age specific national death rates by indirect standardisation and expressed by standardised mortality ratios (SMR). A statistically significant excess has been observed for lung and laryngeal cancer deaths. The Poisson trend test shows a statistically significant trend for the risk of lung cancer death as a function of cumulative radon exposure, assuming a lag time of 5 years; for laryngeal cancer no significant trend has been observed. Poisson regression modelling has been applied to the following exposure groups: < 10 WLM (Working Level Month); 10-49 WLM; 50-149 WLM; 150-299 WLM; > or = 300 WLM; it indicates an increase in the SMR for lung cancer of 0.6% per WLM (standard error: 0.4%) with an estimated intercept at 0 WLM of 1.68 (standard error: 0.4). The distinction of two working periods, differing by their annual radon concentration (before/since 1956) does not modify this exposure-response relationship. This coefficient of risk per unit of exposure is lower than in most of the other uranium miners' studies but it lies in the range of the evaluation of the ICRP 50 committee and the 'BEIR IV' report of the U.S. National Academy of Science. It is observed in a cohort having experienced low cumulative exposure to radon (mean: 70 WLM) spread over a mean duration of 14.5 years. Even though occupational exposure in mines differs in several particulars from domestic exposure, this study presents characteristics of low annual exposure comparable to radon gas concentrations in houses of 500-1000 Bq.m-3, and will contribute to the evaluation of cancer risk for the public. PMID- 8494705 TI - Primary malignant mediastinal germ cell tumours: improved prognosis with platinum based chemotherapy and surgery. AB - A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free. PMID- 8494706 TI - A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia. AB - Patients with breast cancer treated with MPA often report an improvement in appetite. Similar appetite stimulation is seen in patients treated with some corticosteroids, but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect. MPA (100 mg tds orally) has therefore been compared with placebo in 60 patients with advanced malignant disease. Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy. Patients were treated for 6 weeks and were assessed at weeks 0, 3 and 6 for appetite, energy, mood and pain using visual analogue scales. Nutritional status was assessed by the measurement of serum proteins and anthropometrics. Karnofsky score was recorded as a measure of performance status. There was a significant improvement in appetite in the MPA group between weeks 0 (pre-study) and 3 (P = 0.0002) and 0 and 6 (P = 0.015). There was no significant improvement in appetite in the placebo group. Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 (P = 0.023 and P = 0.039 respectively). These two parameters showed no significant change in the placebo group. There was no change in anthropometric measurements, weight, performance status, energy, mood or pain in either group. These data indicate that there was a significant increase in appetite in anorexic patients with advanced cancer treated with MPA which was reflected in increases in rapid turnover proteins reported to reflect nutritional status. However, this apparent increase in appetite did not result in improved weight, performance status, energy levels, mood or relief of pain. Further studies to investigate the effect of higher doses of MPA are indicated. PMID- 8494707 TI - Karyotypic abnormalities in tumours of the pancreas. AB - Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours. PMID- 8494708 TI - Pre- and post-treatment sexual life in testicular cancer patients: a descriptive investigation. AB - Aspects of sexuality were assessed by questionnaires in 76 testicular cancer patients after orchiectomy before further treatment and, respectively, 6, 12 and 36 months after therapy. Before treatment 11% of the patients reported dissatisfaction with sexual life. About 20% of the patients sometimes experienced reduced libido and erectile difficulties. Six months after therapy significantly more patients (27%) recorded an unsatisfactory sexual life as compared to the pretreatment situation. At the 36 months' evaluation 22 of 76 evaluable patients (18%) still stated that their sexual life was inferior to the pretreatment experience. Libido and erectile function decreased transiently during the first year after treatment in most patients. Twelve patients reported permanent 'dry ejaculation' after bilateral retroperitoneal lymph node dissection. Other sexual disturbances could not be related to specified treatment modalities. Increased age at the time of diagnosis and psychological distress tended to correlate with the incidence of sexual problems. For about 60% of the patients the discussion of expected and experienced sexual life problems was an important issue to be discussed before their treatment for testicular cancer and during follow-up. The high frequency of any kind of long-lasting sexual problems (30%), though often of minor degree, warrants an adequate counselling of these patients before and after treatment. PMID- 8494709 TI - Early sCD8 plasma levels during subcutaneous rIl-2 therapy in patients with renal cell carcinoma correlate with response. AB - Plasma sIl-2R and sCD8 levels of 12 patients with renal cell carcinoma were determined before and during subcutaneous rIl-2 therapy. Patients with a complete/partial remission showed a significantly stronger initial increase of sCD8 compared to patients with stable disease or tumour progression. PMID- 8494710 TI - First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer. AB - Estimation of FGF-3 oncogene amplification in DNA samples extracted from paraffin embedded sections of 136 ovarian cancer samples was carried out by a quantitative PCR method. The aim of this study was to elucidate a possible association of FGF 3 copy numbers with established prognostic factors such as age, histology, FIGO stage, grading, postoperative residual tumour mass, ascites, hormone receptor content and preoperative CA 125 serum levels. In addition, correlation of FGF-3 amplification with overall survival of the patients was assessed. There was a borderline positive correlation between preoperative CA 125 serum levels and the degree of amplification of the FGF-3 gene (P = 0.06). A statistically significant association of FIGO-stage with FGF-3 copy number could be found (P = 0.008). No correlation between FGF-3 amplification and overall survival was noted. The data combine to suggest that FGF-3 is an indicator of aggressiveness of ovarian cancer. PMID- 8494711 TI - Activity of type IV collagenases in benign and malignant breast disease. AB - Using zymography and computer assisted image analysis, we have measured the levels of type IV collagenases in biopsies from normal breast, and benign and malignant breast disease. The 92 kDa form was present in three of 11 cases of normal/benign disease, three of nine grade I tumours, four of 12 grade II tumours, but 11 of 11 grade III tumours. Mean levels were higher in grade III tumours (P < 0.0001). When the levels of 72 kDa collagenase and its active 62 kDa form were considered together, there was no difference between the benign and malignant cases (P = 0.55), but the amount of active enzyme, considered as a proportion of the 62 + 72 kDa forms, was significantly higher in malignant disease (P = 0.003). There was also a trend towards a higher proportion of active enzyme with increasing tumour grade (P < 0.0001). In situ hybridisation and immunohistochemistry studies showed that that mRNA and protein for the 92 kDa enzyme was primarily found in the tumour stroma. mRNA for the 72 kDa enzyme was also found in stromal areas. This study demonstrates a clear relationship between production of Type IV collagenases and malignant breast disease. Inhibitors of these enzymes may be of value in preventing metastatic disease. PMID- 8494712 TI - The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer. AB - Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patients and the CA-195 and CA-242 in 78%. All three markers were elevated in 70% and at least one elevated in 93%. CA-195 and CA-242 appeared to be co-expressed, by contrast with the CEA. When compared to the results of serial CT scanning the CEA correlated best with the course of the disease, the positive predictive value being 54% for a partial response, 77% for minor and partial responses combined and 100% for progressive disease. The corresponding values for CA-195 were 46%, 62% and 100% respectively and for CA-242, 50%, 67% and 100% respectively. Thus, although falling levels of markers overestimate the number of responses demonstrated by imaging, rising tumour markers invariably herald progressive disease. This was often evident up to 16 weeks before progression was observed on scanning. CEA is the most useful of the three markers in the monitoring of patients being treated for advanced colorectal cancer, but other markers may prove valuable if the CEA is normal. The use of tumour markers should reduce the need for regular scanning. PMID- 8494713 TI - Multivariate analysis of prognostic factors in patients with non HIV-related primary cerebral lymphoma. A proposal for a prognostic scoring. AB - Between 1982 and 1991, 41 patients were treated for non HIV related primary cerebral lymphoma (PCL) in our institute. The purpose of this study was to perform a multivariate analysis of prognostic factors for survival in these patients. The presence of a CSF protein level over 0.6 g l-1 at diagnosis was found to be the most significant unfavourable prognostic factor in univariate analysis and had not previously been reported. Among the five significant prognostic factors at diagnosis, (age over 60 years, performance status--ECOG scale--over 2, memory dysfunction, non hemispheric tumour site, CSF protein level over 0.6 g l-1 at the diagnosis), three independent factors were identified in multivariate analysis: (1) CSF protein level (P = 0.007; RR = 4.7); (2) PS > 2 (P = 0.04, RR = 2.65); (3) age over 60 (P = 0.08; RR = 2.43). Using the regression coefficient of these three parameters, we determined a prognostic index which allowed us to distinguish three risk groups whose theoretical median survival is 4, 20 and 54, months respectively in patients with non HIV related PCL. These results indicate that PCL is an heterogeneous disease in terms of the prognostic in which three subgroups with discriminant survival can be identified. PMID- 8494714 TI - Effect of rehydration on guaiac-based faecal occult blood testing in colorectal cancer screening. AB - Screening for colorectal cancer by means of unhydrated Hemoccult (HO) is in progress in the Province of Florence since 1982. In 1990 rehydrated HO was introduced in the town of Empoli. Five adjacent municipalities where screening had started in 1987 were selected for comparison. In both areas subjects aged 40 70 were invited by mail to undergo the screening protocol. HO-positive subjects were invited to undergo either pancolonoscopy or a combination of left colonoscopy and double contrast barium enema. HO-negative subjects were invited to repeat screening 2 years later. The positivity rate of HO was significantly higher (P < 0.001) for rehydrated (5%) as compared to unhydrated (3.1%) HO. The positive predictive values for cancer (unhydrated: 5.8%; rehydrated: 8.9%) and for adenomas (unhydrated: 26.7%; rehydrated: 25.5%) did not significantly differ. The detection rates of rehydrated HO were significantly higher as compared to unhydrated HO both for cancer (0.37% vs 0.15%; P < 0.05) and adenomas (1.06% vs 0.72%; P < 0.05%). In the present experience rehydration doesn't produce any decrease in the positive predictive value for cancer or adenomas and the increase in the positivity rate appears quite acceptable when considering the significant increase in the detection rates of cancer and adenomas. We conclude that rehydrated HO should be introduced as the standard test for screening in order to increase sensitivity for colorectal cancer and adenomas. PMID- 8494715 TI - Phosphomonoester is associated with proliferation in human breast cancer: a 31P MRS study. AB - Phospholipid metabolism of human breast cancer was studied by 31P magnetic resonance spectroscopy (MRS). In vivo localised 31P MR spectra were obtained from the tumour alone using phase modulated rotating frame imaging. For 31 tumours, median (range) phosphomonoester (PME) to ATP ratio was 1.48 (0.57-3.78) and phosphodiester (PDE) to ATP ratio was 1.65 (0.44-3.89). DNA index and S phase fraction (SPF) were measured by flow cytometry of paraffin embedded tissue. Twelve (39%) tumours were diploid and 19 aneuploid. Median (range) SPF for 29 assessable tumours was 5.3% (0.6-28%), with significantly greater median SPF for aneuploid tumours (9.3%) than diploid (3.8%, P = 0.007). There was a significant association between PME/ATP and SPF (P = 0.03) due to a significant correlation for aneuploid tumours (P = 0.01). High resolution 31P MRS of extracts from 18 tumours (including seven studied in vivo) demonstrated that the PME peak consists predominantly of phosphoethanolamine (PE) with a smaller contribution from phosphocholine (PC) (median (range) PE/PC: 3.02 (1.13-5.09)). Changes in PME/ATP were observed for two tumours where tamoxifen stablized disease and may be consistent with the cytostatic effects of this drug. PMID- 8494716 TI - Phenoxy herbicides, chlorophenols, soft-tissue sarcoma (STS) and malignant lymphoma. PMID- 8494717 TI - 5-FU toxicity and nutritional deficiencies. PMID- 8494718 TI - Antisense technology for cancer therapy: does it make sense? PMID- 8494720 TI - A rodent model for testicular involvement in acute lymphoblastic leukaemia. AB - The testis is the third common site of relapse after primary treatment of childhood acute lymphoblastic leukaemia, but in adults relatively few testicular relapses of acute lymphoblastic leukaemia have been reported. In the present investigation the differences in the behaviour of leukaemia in immature and mature rat testis and the interactions of testicular and leukaemic cells were studied. Intraperitoneal injection of rat T-leukaemic cells to sexually immature animals induced testicular infiltrations in 100% of animals in 17 days. The infiltrations were small and located perivascularly in the interstitial tissue. Intraperitoneal injection of T-leukaemic cells to sexually mature animals induced testicular infiltrates in 42% of the animals. Leukaemic cells injected directly to the lymph sinusoids of sexually immature and mature testis proliferated rapidly causing testicular enlargement. The M(r) > 5 K fraction of extracts of 50 days old normal rat testes inhibited 3H-TdR incorporation of both normal and leukaemic ConA-stimulated rat lymphoblasts significantly. The same fraction of extracts of testes of 25 days old rats did not have any effect on 3H-TdR incorporation. The normally occurring pubertal increase in the lymphocyte inhibitory effect of the M(r) > 5 K fraction of testis extracts on 3H-TdR incorporation of PBL was prevented following either intraperitoneal or intratesticular injection of rat leukaemic lymphoblasts administered at the age of 25 days. The present observations suggest that physiological pubertal changes in the permeability of vascular endothelium and immunosuppressive effect of the testis may be important explanatory factors for the smaller number of testicular relapses in men compared to boys seen after treatment of ALL. PMID- 8494719 TI - Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation. AB - Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID- 8494721 TI - Inhibition by a new bisphosphonate (YM175) of bone resorption induced by the MBT 2 tumour of mice. AB - A new bisphosphonate, disodium dihydrogen (cycloheptylamino) methylene bisphosphonate monohydrate (YM175), was compared with 3-amino-1 hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1 bisphosphonate (HEBP) in terms of its effect on tumour induced osteolysis using a bladder tumour in mice (MBT-2). The method consisted of inoculating tumour cells subcutaneously (SC) over the calvaria in mice, resulting in a local tumour causing fragmentation of the bone. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumour. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histology. The results showed the following sequence of potency: YM175 > AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumour. YM175 appears to be an interesting new bisphosphonate with possible clinical application. PMID- 8494722 TI - Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers. AB - Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA-PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm and occlusion probably due to thrombi formation. Oedema was notable, especially following PDT with 600 J cm-2 at 24 h p.i. PMID- 8494723 TI - The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis. AB - It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel. PMID- 8494724 TI - Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes. AB - Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co localisation and co-growth in nude mice by taking advantage of the sensitivity of the histochemical marker genes for localising them. After intravenous co injection of equal numbers of both cells to analyse experimental metastasis, most foci transiently established in the lung for several hours were comprised of only one cell class. However, a significant fraction of foci contained both cell types, as identified in double-stained whole-lung tissues and in lung sections. Evidence was obtained that LZEJ cells increase the survivability and subsequent growth of APSI-containing micrometastases during co-localisation in lung, when compared to APSI cells injected alone. Conversely, APSI cells facilitate expansion of LZEJ cells from micrometastatic foci into overt-metastatic nodules in the lung. These analyses reveal reciprocity during experimental metastasis by two related tumour cell classes derived from the same parental cell. PMID- 8494725 TI - Detection of bcl-2/JH rearrangement in follicular and diffuse lymphoma: concordant results of peripheral blood and bone marrow analysis at diagnosis. AB - The capacity to detect t(14;18) breakpoints in non-Hodgkin's lymphoma (NHL) peripheral blood and bone marrow was studied by DNA PCR. We studied 33 patients with follicular lymphoma (FL) (Working Formulation subtypes B, C, D) and 38 patients with intermediate-grade NHL (subtypes F, G). In the FL subgroup, 86% of the morphologically-positive bone marrow patients had amplifiable t(14;18) breakpoints by PCR. Remarkably, of 19 FL patients with 'negative' bone marrows, 11 (58%) were PCR-positive. In addition, half of the early clinical stage patients (I and II) had detectable breakpoints in their bone marrow DNA. Samples from NHL patients with intermediate-grade disease exhibit the same phenomena but at a considerably lower frequency. Paired peripheral blood and bone marrow samples were available at diagnosis in a subset of 56 patients. The concordance between bone marrow and peripheral blood PCR findings was high, with peripheral blood of 55/56 showing the same PCR results as the corresponding bone marrow. PMID- 8494726 TI - Mechanisms of selective killing of neuroblastoma cells by natural killer cells and lymphokine activated killer cells. Potential for residual disease eradication. AB - Widely disseminated neuroblastoma in children older than infancy remains a very poor prognosis disease. Even the introduction of marrow ablative chemotherapy with autologous rescue has not significantly improved the outlook for these children, presumably because of a failure to eradicate minimal residual disease. One additional approach which may hold promise is the use of immunomodulation with cytokines such as IL2 in the setting of minimal residual disease (MDR), for example after intensive chemotherapy and ABMT. However, considerable variability in the susceptibility of neuroblastoma cells to natural killer (NK) and lymphokine-activated (LAK) killing has been observed, and it is presently unclear how NK and LAK cells recognise neuroblastoma cells. In this paper we examine expression of cell adhesion molecules on neuroblastoma to determine which of these modify interaction with NK and LAK cells. We find that LFA-3 (CD58), the ligand for CD2 is of predominant importance in predicting susceptibility of neuroblastoma to the cytotoxic actions of NK and LAK cells, while expression of ICAM-1 (CD54) may also modify susceptibility. These findings were confirmed by blocking experiments in which co-culture of target cells with ICAM-1 and LFA-3 reduced LAK and NK cytotoxicity. Study of the immunophenotypic features of each patient's neuroblastoma cells before induction of MRD may be valuable in determining the likely effect of IL2 in predicting disease reactivation. PMID- 8494727 TI - Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice. AB - HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 10(6) ml-1) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ng ml-1 within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-IL6 cells were transplanted into C57BL/6 mice subcutaneously, the mean +/- s.d. of survival times of these mice were 33.3 +/- 9.7, 34.3 +/- 7.1 and 17.0 +/- 3.1 days, respectively. The survival time of LLC-IL6 cells transplanted mice was significantly shorter than that of LLC (P < 0.01) or LLC-Neo (P < 0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-IL6 transplanted mice than in LLC transplanted mice. Mouse IL-1 alpha and mouse TNF-alpha were not detected in the plasma of LLC-IL6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-1 alpha and TNF-alpha in the plasma. This state may be responsible for the shortened survival of LLC-IL6 tumour-bearing mice. PMID- 8494729 TI - Effect of reconstituted basement membrane components on the growth of a panel of human tumour cell lines in nude mice. AB - Previous reports have indicated that reconstituted basement membrane (matrigel), when co-injected with either established or primary human tumour cells, can improve the growth of subcutaneous xenografts in nude mice. The human adenocarcinoma cell lines A549, SW480, and WiDr, and the human fibrosarcoma cell line HT1080scc2 exhibit varying degrees of tumourigenicity in nude mice. All these lines showed increased tumorigenicity and/or growth rate, together with a change towards a more differentiated tissue morphology, when co-injected with matrigel into nude mice. Experiments using A549 cell line have indicated that the effect of matrigel is concentration-dependent and that increased growth rate is not maintained when xenografts grown with matrigel are passaged into further mice. These results strongly suggest that increased tumour growth results from the improved growth conditions afforded by matrigel, rather than from the selection of subpopulations of the most tumourigenic cells. Increased growth of intracaecal tumours arising from the co-injection of SW480 cells with matrigel, indicate a possible use for matrigel in the development of more relevant animal models using the orthotopic site. Purified laminin significantly increased the growth of sc tumours resultant from co-injection with either WiDr or A549 cells, whereas collagen IV or laminin with entactin showed no such effect. A role for free laminin in the stimulation of cell growth in the absence of an intact basement membrane is discussed. PMID- 8494728 TI - Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. AB - There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogesterone acetate (MPA) on MCF-7 cell proliferation. The 19 norprogestins stimulated proliferation at a concentration of 10(-8) M, while MPA could not stimulate proliferation at concentrations as great as 3 x 10(-6) M. The stimulatory activity of the 19-norprogestins could be blocked by the antioestrogen ICI 164,384, but not by the antiprogestin RU486. Transfection studies with the reporter plasmids containing an oestrogen response element or progesterone response element (vitERE-CAT, pS2ERE-CAT, and PRE15-CAT) were performed to determine the intracellular action of norgestrel and gestodene. The 19-norprogestins stimulated the vitERE-CAT activity maximally at 10(-6) M, and this stimulation was inhibited by the addition of ICI 164,384. MPA did not stimulate vitERE-CAT activity. A single base pair alteration in the palindromic sequence of vitERE (resulting in the pS2ERE) led to a dramatic decrease in CAT expression by the 19-norprogestins, suggesting that the progestin activity required specific response element base sequencing. PRE15-CAT activity was stimulated by norgestrel, gestodene and MPA at concentrations well below growth stimulatory activity. This stimulation could be blocked by RU486. These studies suggest that the 19-norprogestins norgestrel and gestodene stimulate MCF-7 breast cancer cell growth by activating the oestrogen receptor. PMID- 8494730 TI - In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA). AB - The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the interactions ranging from antagonistic to synergistic in terms of the multiplicative concept for drug interactions. However, an 'additive' model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) for several common antileukaemic drug combinations. When the two interaction models were related to treatment outcome 38% of the non-responders showed preference for the additive model whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the most active single component. Direct comparison of Dmax and the combination for correlation with clinical outcome demonstrated only minor differences in the ability to predict drug resistance. The results show that FMCA appear to report drug interactions in samples from patients with AML in accordance with clinical experience. Furthermore, testing single agents as a substitute for drug combinations may be adequate for detection of clinical drug resistance to combination therapy in AML. PMID- 8494731 TI - Augmentation of tumour delivery of macromolecular drugs with reduced bone marrow delivery by elevating blood pressure. AB - Effects of angiotensin II (AT-II)-induced hypertension on the distribution of macromolecules to Walker carcinoma and to bone marrow of SMANCS [poly(styrene-co maleic-acid)-neocarzinostatin conjugate] were investigated in rats. AT-II-induced hypertension from about 100 to 150 mmHg significantly increased the accumulation of the macromolecular drug SMANCS and 51Cr-labelled bovine serum albumin ([51Cr]BSA), representatives of macromolecular drugs, in tumour tissue. At 1 h after i.v. administration, intratumour concentrations of [51Cr]BSA and SMANCS were elevated by 1.2-1.8-fold. The higher drug accumulation in the tumour that was produced by the artificial hypertension was retained even 6 h after administration. This observation indicates an additive effect to that under normotensive conditions where intratumour macromolecular drug concentrations increase steadily during this period. Furthermore, distributions of these drugs in the bone marrow and the small intestine decreased during artificial hypertension to 60-80% of those in the normotensive state. Therefore, the drug concentration ratios of tumour/bone marrow and tumour/small intestine were increased by 1.8-2.4-fold. A decreased distribution of SMANCS to normal tissues under hypertensive conditions was also confirmed by the significant reduction of its toxicity e.g. leukopenia, diarrhoea, and body weight loss, even at a lethal dose. On the contrary, [3H]methylglucose showed no remarkable difference in tumour or bone marrow accumulation under this hypertensive condition. These results show the advantages of macromolecules over small molecules for AT-II induced hypertension chemotherapy. PMID- 8494732 TI - Modification of tumour blood flow using the hypertensive agent, angiotensin II. AB - The effects of different doses of angiotensin II (0.02 to 0.5 microgram kg-1 min 1 on mean arterial blood pressure, tissue blood flow and tissue vascular resistance were investigated in BD9 rats. Blood flow was measured using the uptake of 125I- or 14C-labelled iodoantipyrine (125I-IAP and 14C-IAP). Spatial heterogeneity of blood flow within tumours, before and after angiotensin II infusion, was also measured using 14C-IAP and an autoradiographic procedure. Mean arterial blood pressure rose steeply with angiotensin II dose. Blood flow to skeletal muscle, skin overlying the tumour, contralateral skin, small intestine and kidney tended to decline in a dose-dependent manner. Blood flow to the tumour was also reduced (to 80% of control values) but there was no dose response. Blood flow to the heart was slightly increased and blood flow to the brain was unaffected by angiotensin II. Vascular resistance, in all tissues, was increased by angiotensin II infusion. The increase in tumour tissue was similar to that found in skeletal muscle and small intestine and is likely to be caused by a direct vasoconstricting effect of the drug rather than autoregulation of tumour blood flow in the face of an increase in perfusion pressure. The reduction in overall blood flow at the highest perfusion pressure was due to a preferential effect of angiotensin II at the tumour periphery. These results show that some tumours, at least, can respond directly to the effects of vasoactive agents. PMID- 8494733 TI - Lack of nephrotoxicity of oral ammine/amine platinum (IV) dicarboxylate complexes in rodents. AB - The comparative nephrotoxicity of i.v. cisplatin, i.v. carboplatin and six p.o. ammine/amine Pt(IV) dicarboxylates was studied in rodents following single MTD treatments. In mice, i.v. cisplatin caused proteinuria (1 g l-1), glycosuria (16.7 mM) and decreased GFR at 4 days, and histological kidney damage with onset at 6 days. In contrast, mice treated with i.v. carboplatin or p.o. ammine/amine Pt(IV) dicarboxylates had urinary glucose, urinary protein, GFR and kidney histology within the control range. In rats, i.v. cisplatin caused 5-fold elevations in plasma creatinine (188 +/- 33 microM) and urea (30.4 +/- 8.9 mM), a 10-fold fall in creatinine clearance (0.54 +/- 0.31 ml min-1 kg-1), a 25-fold elevation in urine/plasma glucose concentration ratio (3.28 +/- 0.17), a 20% increase in kidney weight (7.9 +/- 0.56 mg gm-1 body weight) and extensive histological damage 4 days after treatment. In contrast, i.v. carboplatin and p.o. JM216 (the lead compound of this series) caused neither abnormalities in renal function nor histological damage in rats. The nephrotoxicity of single MTD treatments of p.o. ammine/amine Pt(IV) dicarboxylate complexes appears less than i.v. cisplatin and comparable to i.v. carboplatin. PMID- 8494734 TI - Treponema denticola (ex Brumpt 1925) sp. nov., nom. rev., and identification of new spirochete isolates from periodontal pockets. AB - Standard growth and isolation methods were used to obtain five new treponema strains in pure culture from deep periodontal pockets. The strains were identified to the species level by various methods, including agglutination, immunofluorescence, a dot blot immunoassay, electron microscopy, gas-liquid chromatography of metabolic volatile fatty acids, and DNA hybridization. Two isolates were strains of Treponema socranskii; the other three were strains of "Treponema denticola," a species described in 1925 by Brumpt. Because no type strain was designated for this species previously, the name was not included on the Approved Lists of Bacterial Names and has no current nomenclatural standing. We propose that Treponema denticola (ex Brumpt) sp. nov., nom. rev. is a valid and distinct species of the genus Treponema and designate strain ATCC 35405 as the type strain and strains ATCC 33520 and ATCC 35404 as reference strains. T. denticola appears to be the species that is most frequently isolated from periodontal pockets. Unless new isolation and cultivation techniques are introduced, it appears that present technology can yield only isolates belonging to the currently described oral anaerobic spirochete species and that there is little chance of isolating the larger treponemes. PMID- 8494735 TI - Mycobacterium intermedium sp. nov. AB - Strains of a new type of slowly growing mycobacterium were repeatedly isolated from sputum from a patient with pulmonary disease. This photochromogenic organism grew at 22, 31, 37, and 41 degrees C, possessed catalase, acid phosphatase, esterase, beta-galactosidase, and arylsulfatase activities, and hydrolyzed Tween. It did not produce nicotinic acid or have nitrate reductase, acetamidase, benzamidase, isonicotinamidase, nicotinamidase, pyrazinamidase, succinidamidase, and acid phosphatase activities. Urease activity was variable. The organism is susceptible to ethambutol and resistant to isoniazid and streptomycin. A mycolic acid analysis revealed the presence of alpha-mycolates, alpha'-mycolates, and keto-mycolates. The results of comparative 16S rRNA sequencing placed this organism at an intermediate position between the rapidly and slowly growing mycobacteria. On the basis of the pattern of enzymatic activities and metabolic properties, the results of fatty acid analyses, and the unique 16S rRNA sequence, we propose that this organism represents a new species, for which we propose the name Mycobacterium intermedium. The type strain is strain 1669/91; a culture of this strain has been deposited in the Deutsche Sammlung von Mikroorganismen und Zellkulturen as strain DSM 44049. PMID- 8494736 TI - Relatedness of three species of "false neisseriae," Neisseria caviae, Neisseria cuniculi, and Neisseria ovis, by DNA-DNA hybridizations and fatty acid analysis. AB - DNA-DNA hybridization was used to determine the levels of genomic relatedness of the three species of "false neisseriae," Neisseria caviae, Neisseria cuniculi, and Neisseria ovis. The reference strains of these species exhibited high levels of intraspecies relatedness (93 to 100% for N. caviae, 79 to 100% for N. cuniculi, and 68 to 100% for N. ovis) but low levels of interspecific relatedness (less than 34%) to each other and to various species belonging to the beta subclass of the Proteobacteria (Kingella kingae, Neisseria gonorrhoeae, Neisseria meningitidis, and Oligella urethralis) or to the gamma subclass (Branhamella catarrhalis, Kingella indologenes, Moraxella atlantae, Moraxella bovis, Moraxella lacunata subsp. lacunata, Moraxella lacunata subsp. liquefaciens, Moraxella nonliquefaciens, Moraxella osloensis, and Moraxella phenylpyruvica). However, the levels of DNA-DNA hybridization for the three species of "false neisseriae" were significantly higher with the species belonging to the gamma subclass (average, 13.7%) than with the species belonging to the beta subclass (average, 4.5%). These data suggest that N. caviae, N. cuniculi, and N. ovis are three separate genomic species in the gamma subclass. An ascendant hierarchical classification based only on fatty acid profiles distinguished four main classes containing (i) most of the "classical moraxellae," the "false neisseriae," and B. catarrhalis, (ii) only Acinetobacter spp., (iii) M. nonliquefaciens and "misnamed moraxellae" (M. atlantae, M. osloensis, and M. phenylpyruvica), and (iv) the "true neisseriae," the three Kingella species, and O. urethralis. Fatty acids that distinguish these four classes were identified. The fatty acid profiles of the two strains of Psychrobacter immobilis which we studied are not very similar to the profiles of the other taxa. Our results support the hypothesis that the three species of "false neisseriae," B. catarrhalis, the "classical moraxellae," and Acinetobacter spp. should be included in the same family. PMID- 8494737 TI - Characterization of Bacillus brevis with descriptions of Bacillus migulanus sp. nov., Bacillus choshinensis sp. nov., Bacillus parabrevis sp. nov., and Bacillus galactophilus sp. nov. AB - Thirty-five Bacillus brevis strains obtained from culture collections, including protein-producing isolates, were taxonomically studied by using numerical analysis, DNA base composition, and DNA-DNA hybridization. Six DNA relatedness groups were represented, and these groups correlated well with clusters based on the numerical analysis. The B. brevis strains were separated into B. brevis sensu stricto, four new species, and an unidentified species of the genus Bacillus. Bacillus migulanus sp. nov., Bacillus choshinensis sp. nov., Bacillus parabrevis sp. nov., and Bacillus galactophilus sp. nov. are proposed. PMID- 8494738 TI - Comparative study of "Micrococcus sp." strains CCM 168 and CCM 1405 and members of the genus Salinicoccus. AB - Two culture collection strains, CCM 168 and CCM 1405, previously assigned to the genus Micrococcus were shown by molecular chemical characterization to belong to the genus Salinicoccus. A more detailed comparison of the physiological and biochemical properties of these strains and comparison with the type strain of Salinicoccus roseus indicated high degrees of relatedness among the three strains. DNA-DNA hybridization studies confirmed the high degrees of relatedness. All of the data demonstrate quite clearly that strains CCM 168 and CCM 1405 are members of the species S. roseus. PMID- 8494739 TI - Taxonomic study of Corynebacterium Group ANF-1 strains: Proposal of Corynebacterium afermentans sp. nov. containing the subspecies C. afermentans subsp. afermentans subsp. nov. and C. afermentans subsp. lipophilum subsp. nov. AB - We have determined the cell wall composition, guanine-plus-cytosine (G+C) contents of the DNA, rRNA gene restriction patterns, and the levels of DNA-DNA relatedness of 11 strains identified biochemically as Centers for Disease Control (CDC) Corynebacterium group absolute nonfermenter 1 (Corynebacterium group ANF 1). For seven of these strains, growth is abundant on 5% sheep blood agar, which differentiates them from the four other strains, whose growth requires a lipid supplement such as Tween 80. Two of the lipid-requiring strains produced mucoid colonies on 1% Tween 80-supplemented sheep blood agar. All strains possess cell wall component type IV, short-chain mycolic acids, and G+C contents of DNA of 66 to 68 mol% as determined by reverse-phase high-performance liquid chromatography. DNA-relatedness experiments by an S1 nuclease procedure showed that nine of these strains, including two of the lipid-requiring strains, constitute a new genomic species less than 40% related to Corynebacterium species and other coryneform groups. The lipid-requiring strain T18502 exhibited 98% DNA relatedness with another lipid-requiring strain, T88593 (difference in thermal denaturation midpoint [delta Tm] = 2 degrees C) and 71 to 77% similarity with the nonlipophilic strains (delta Tm range of from to 5 degrees C). Conversely, the DNA relatedness between strain LCDC 88199 and the six other nonlipophilic strains ranged from 86 to 100% (delta Tm range of from 1 to 3 degrees C) and was only 73 and 76% with the lipophilic strains T18502 and T88593, respectively (delta Tm, 3 and 4 degrees C). These results indicated that these two cultural types of bacteria constitute two subspecies within the new genomic species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494740 TI - Kibdelosporangium albatum sp. nov., producer of the antiviral antibiotics cycloviracins. AB - A new species of the genus Kibdelosporangium is described. This soil organism forms long straight spore chains and numerous sporangium-like structures on the aerial mycelium. The new species has type IV cell walls and pattern A whole-cell sugars (meso-diaminopimelic acid, arabinose, and galactose are present), type PII phospholipids, MK-9(H4) as the major menaquinone, and no mycolic acids. On the basis of morphology and chemotaxonomy, the single isolate is assigned to the genus Kibdelosporangium. The isolate differs from two previously described species of the genus in fatty acid composition, the absence of melanin formation, and many physiological and biochemical characteristics and is identified as a new species. Accordingly, the name Kibdelosporangium albatum sp. nov. is proposed for this isolate. The type strain is R761-7 (= ATCC 55061). PMID- 8494741 TI - Eubacterium saphenum sp. nov., isolated from human periodontal pockets [corrected]. AB - A new species, Eubacterium saphenum [corrected] sp. nov., established on the basis of the results of DNA-DNA hybridization, was proposed for strains isolated from human periodontal pockets. Differential characteristics are given. PMID- 8494742 TI - Phylogenetic analysis of rhizobia and agrobacteria based on 16S rRNA gene sequences. AB - The phylogenetic relationships of members of the genera Rhizobium, Agrobacterium, Bradyrhizobium, and Azorhizobium were studied by direct sequencing of their amplified 16S rRNA genes. Comparative analysis of the sequence data confirmed that the genera Bradyrhizobium and Azorhizobium belong to distinct phylogenetic lineages. The genera Rhizobium and Agrobacterium were found to be phylogenetically heterogeneous, and several subgroupings in which Rhizobium and Agrobacterium species were intermixed were evident. The present findings show that the genus and species definitions of these organisms are in need of revision. Different possibilities for this are discussed in the light of sequencing data. PMID- 8494743 TI - Five new Legionella species isolated from water. AB - Fourteen Legionella-like strains isolated from aquatic sources have been characterized serologically, biochemically, and in terms of DNA relatedness. The strains grew on buffered charcoal-yeast extract agar but not on blood agar and displayed phenotypic characteristics typical of the family Legionellaceae, including a requirement for cysteine, cellular fatty acid compositions in which branched-chain acids predominate, and the possession of isoprenoid quinones of the ubiquinone series with more than 10 isoprene units in their side chains. All were nonfermentative, lacked urease, were incapable of nitrate reduction, and reacted positively with a DNA probe specific for the Legionellaceae. DNA hybridization studies in which the hydroxyapatite method was used demonstrated that the strains represented five new species of the genus Legionella. Nine of the strains were more than 90% interrelated, and the name Legionella londiniensis sp. nov. is proposed for this group. Two strains formed a second hybridization group, for which the name Legionella nautarum sp. nov. is proposed, while the three remaining species, Legionella geestiana sp. nov., Legionella quateirensis sp. nov., and Legionella worsleiensis sp. nov., are each represented by a single strain. The levels of relatedness of the new species to each other are 23% or less, and the levels of relatedness to other members of the genus ranged from 0 to 36%. L. geestiana, L. nautarum, and L. londiniensis are serologically unrelated to all other known Legionella species. L. worsleiensis cannot be separated from Legionella pneumophila serogroup 4 by serological methods and is also serologically indistinguishable from L. quateirensis; distinctions may be made on the basis of fatty acid composition and biochemical reactions. PMID- 8494744 TI - Transfer of Thiosphaera pantotropha to Paracoccus denitrificans. AB - Comparative sequence analysis of in vitro-amplified 16S rRNA genes of Thiosphaera pantotropha GB17T (T = type strain) and Paracoccus denitrificans LMG 4218T revealed identical 16S rRNA primary structures for the two organisms. The level of overall DNA similarity of Thiosphaera pantotropha GB17T and P. denitrificans DSM 65T is 85%, as determined by quantitative DNA-DNA hybridization. Therefore, we propose the transfer of Thiosphaera pantotropha to P. denitrificans. The closest relative of Thiosphaera pantotropha and P. denitrificans is Thiobacillus versutus, as revealed by comparative 16S rRNA sequence analysis. These organisms are members of the alpha subclass of the Proteobacteria. Within this subclass, Thiosphaera pantotropha, P. denitrificans, and Thiobacillus versutus form a phylogenetic group with Rhodobacter sphaeroides, Rhodobacter capsulatus, and "Erythrobacter longus." PMID- 8494745 TI - Phylogeny of Metschnikowia species estimated from partial rRNA sequences. AB - Phylogenetic relationships of species assigned to the genus Metschnikowia were estimated from the extents of divergence among partial sequences of rRNA. The data suggest that the aquatic species (Metschnikowia australis, Metschnikowia bicuspidata, Metschnikowia krissii, and Metschnikowia zobellii) and the terrestrial species (Metschnikowia hawaiiensis, Metschnikowia lunata, Metschnikowia pulcherrima, and Metschnikowia reukaufii) form two groups within the genus. M. lunata and M. hawaiiensis are well separated from other members of the genus, and M. hawaiiensis may be sufficiently divergent that it could be placed in a new genus. Species of the genus Metschnikowia are unique compared with other ascomycetous yeasts because they have a deletion in the large-subunit rRNA sequence that includes nucleotides 434 to 483. PMID- 8494746 TI - Reclassification of American Rhizobium leguminosarum biovar phaseoli type I strains as Rhizobium etli sp. nov. AB - A new Rhizobium species that nodulates Phaseolus vulgaris L. is proposed on the basis of a sequence analysis of 16S ribosomal DNA. This taxon, Rhizobium etli sp. nov., was previously named Rhizobium leguminosarum biovar phaseoli (type I strains) and is characterized by the capacity to establish an effective symbiosis with bean plants, the reiteration of the nitrogenase structural genes, the organization of the common nodulation genes into two separate transcriptional units bearing nodA and nodBC, the presence of the polysaccharide inhibition gene, psi, and the 16S ribosomal DNA sequence. An analysis of the sequence of a fragment of the 16S rRNA gene shows that this gene is quite different from the gene of R. leguminosarum. In addition, all R. etli strains have identical sequences. We describe these analyses and discuss additional evidence supporting our proposal. PMID- 8494747 TI - The phylogenetic position of Helicobacter nemestrinae. AB - Comparison of the Helicobacter nemestrinae 16S ribosomal DNA with published homologous sequences from members of the genera Helicobacter, Wolinella, and Campylobacter reveals a close relationship between H. nemestrinae, H. pylori, and H. acinonyx. This finding is unexpected since these species differ significantly in their DNA guanine-plus-cytosine contents (24 to 38 mol%). PMID- 8494748 TI - An immunohistological study of desmosomal components in pemphigus. AB - Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which there is loss of cohesion between keratinocytes (acantholysis) and blistering within the epidermis. PV is characterized by acantholysis predominantly between the epidermal basal cells and suprabasal layers, whereas in PF intraepidermal cleavage is higher in the epidermis. Adhesion between keratinocytes is dependent on the function of transmembrane glycoproteins of the cadherin family present in specialized adhesion junctions, the desmosomes. The pathogenesis of acantholysis in pemphigus is uncertain, but the pemphigus autoantibodies bind to epithelial cadherins. We have used monoclonal antibodies to desmosomal components to investigate their distribution in different forms of pemphigus. Our results show that the localization of desmosomal components is abnormal in intact perilesional epidermis, intact epidermis above the blisters in PV and intact epidermis below the blisters in PF. We suggest that autoantibody binding may have a direct effect on the function of specific epithelial cadherins, but will only cause cell separation where the antigen is the principal adhesion molecule. PMID- 8494749 TI - IgE and its related phenomena in bullous pemphigoid. AB - This study was designed to analyse IgE and its related phenomena in bullous pemphigoid (BP). We analysed 17 BP sera by indirect immunofluorescence (IIF) and immunoblotting (IB) using a monoclonal antibody to IgE. In addition, inflammatory cells in lesional skin from 11 patients with BP were analysed by the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies to IgE and Fc epsilon RII/CD23. IgE class anti-basement membrane zone (BMZ) autoantibody was detected in nine of 17 sera (52.9%) by IIF. IgG class anti BMZ antibody could block the BMZ-binding reactivity of IgE class antibody. Titres of IgE class autoantibody in the sera ranged from 1:40 to 1:320, and statistically correlated with serum IgE levels. Two of 11 sera contained an IgE class autoantibody which recognized a 230-kDa BP antigen by IB. By radio allergosorbent test (RAST), IgE-specific antibodies to an extended series of common inhalant and food allergens were detectable in six sera with high concentrations of total IgE (over 3,300 IU/ml). IgE-bearing and Fc epsilon RII expressing cells were demonstrated in the upper dermis and along the BMZ in seven of 11 biopsy specimens by the APAAP technique. The distribution and number of IgE bearing cells in the lesions were similar to those of the Fc epsilon RII expressing cells. These results suggest that both IgE-mediated immune responses and autoimmunity characterize BP as distinctive features. PMID- 8494750 TI - Morphological and biochemical characteristics of trichothiodystrophy-variant hair are maintained after grafting of scalp specimens on to nude mice. AB - Trichothiodystrophy (TTD) is a hair defect associated with abnormal composition of the high-sulphur proteins (HSP). HSP can be modified quantitatively (reduced amount of qualitatively normal HSP: TTD-variant) and qualitatively (TTD). In this study we show that the amino acid composition of hairs collected from the scalp of a patient with TTD-variant (donor) was preserved in hairs produced by donor scalp follicles maintained up to 6 months as grafts on to nude mice. It is the first time that an exceptionally rare, clinically and biochemically well characterized hair dysplasia has been maintained under laboratory conditions for a long period of time. The linear growth rate of TTD-variant hairs was similar to that of control hairs grown under comparable conditions. The persistence of disease-specific abnormalities in the hair shaft indicates that the TTD-variant mutation is expressed without significant quantitative modifications, and appears independent of systemic host-related factors. This model may serve as a clinically relevant working platform for evaluating regulation of abnormal gene expression in the hair follicle under well-controlled experimental conditions. PMID- 8494751 TI - Gamma delta T lymphocytes in oriental cutaneous leishmaniasis: occurrence and variable delta gene expression. AB - It has been suggested that T lymphocytes expressing gamma delta T-cell receptors could play an important role in defence against some intracellular infectious pathogens. The present study was undertaken to characterize the occurrence and variable delta gene expression of T lymphocytes expressing the gamma delta T-cell receptor in oriental cutaneous leishmaniasis. Eleven cases of oriental cutaneous leishmaniasis were investigated by immunohistological analysis using an alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. In three cases, we observed an increased percentage of gamma delta T cells (about 20% of CD3+ cells). In these cases gamma delta T cells generally expressed the V delta 2 segment, and only rarely the V delta 1 gene product. V delta 2+ cells were predominantly localized in the dermis, and were virtually absent in the epidermal compartment. The rare gamma delta T cells observed in the epidermis were almost exclusively V delta 1+. This study demonstrates that an increase of gamma delta T cells may be found in oriental cutaneous leishmaniasis, although it is not a constant feature of the disease. The finding of a preferential expansion of the V delta 2 subset suggests that this subpopulation of gamma delta T cells might be selectively involved in the recognition of Leishmania antigens. The distinct compartmentalization of gamma delta T-cell subpopulations indicates that these subsets may recognize distinct sets of antigens. PMID- 8494752 TI - T cells migrate to tumour sites after extracorporeal interleukin 2 stimulation and reinfusion in a patient with metastatic melanoma. AB - Peripheral blood mononuclear cells (PBMC) were taken by leukapheresis from a patient with melanoma skin metastases and stimulated in vitro using 1000 IU recombinant interleukin 2 (IL-2)/ml to generate lymphokine-activated killer cells (LAK cells). Two-colour immunofluorescence analysis demonstrated an IL-2-induced up-regulation of CD25 on natural killer cells (CD56+) as well as on T lymphocytes (CD3+). After radiolabelling with indium-111, the cells were reinfused. Gamma camera imaging revealed an enrichment at the tumour sites. Immunostaining of tumour tissue taken before and after scintigraphy demonstrated CD25+ T lymphocytes (CD2+, CD3+), but no natural killer cells (CD16+, CD56+) infiltrating the metastases. LAK cell enrichment at melanoma metastases in vivo did not involve natural killer cells, but was characterized by increased numbers of activated T lymphocytes in this patient. PMID- 8494753 TI - Concentrations of nitrogen mustard in the air during topical treatment of patients with mycosis fungoides. AB - Acute and chronic side-effects have been reported during topical treatment of mycosis fungoides with nitrogen mustard (HN2). In order to estimate the risk for the nurse applying topical HN2, the concentration of HN2 in the air during treatment was measured. Air samples were obtained before, and during the 20-min treatment period close to the nurse and patient, and continuously at a distance of 1 m from the patient. The mean concentration of HN2 in the air during treatment was 0.036 mg/m3. Immediately after treatment the concentration dropped to 0.004 mg/m3. The mean cumulative concentration in the room during the 3 1/2 h of the experiment was 0.012 mg/m3. If the MAC (maximal allowable concentration) value of 0.05 mg/m3 for the comparable sulphur mustard is used as a guideline, then with a treatment procedure of 20 min this level is not exceeded. Nevertheless, it is important to minimize the exposure of nursing staff to HN2. PMID- 8494754 TI - Allergy to systemic and intralesional corticosteroids. AB - In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra-articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1-3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice. PMID- 8494755 TI - Melanoma and skin cancer: evaluation of a health education programme for secondary schools. AB - The effectiveness of an education package for secondary schools about the sun and skin cancer was assessed using questionnaires. A variety of teaching methods was used, including pamphlets, workbooks, and a video. The effect of this material was assessed by asking pupils to complete questionnaires immediately after receiving the package (July), and after the summer holiday (September). Five hundred and forty-three children from seven schools were recruited into the study. Results of the questionnaire demonstrated a significant difference in knowledge (P < 0.001) and reported attitude (P < 0.001) compared with a control group. There was no significant difference in behaviour of the taught groups compared with the control group. The only significant activity associated with increased knowledge was wearing a sunscreen (P < 0.005). In contrast, in terms of attitude, those who covered up in the sun (P < 0.0001), wore a sunscreen (P < 0.004), and sat in the shade (P < 0.02), had significantly better attitudes than those who did not behave in this way. This project is a first attempt to assess health education in schools, and reports changes in knowledge, attitudes, and some aspects of behaviour. Adolescents are a group who are difficult to influence, but our study has produced some useful information about how these children respond to such teaching measures. PMID- 8494756 TI - Paraneoplastic pemphigus in a child with a T-cell lymphoblastic lymphoma. AB - We report a child with a T-cell lymphoblastic lymphoma, and a widespread erosive mucocutaneous eruption, whose clinical and immunopathological features were consistent with a diagnosis of paraneoplastic pemphigus. Direct immunofluorescence showed deposition of C3 in the epidermal intercellular spaces, and in a linear pattern along the dermo-epidermal junction. Circulating autoantibodies binding in a pemphigus-like pattern to mouse urinary bladder epithelium were found. By Western immunoblotting, the patient's serum recognized two epidermal polypeptides with molecular weights of 210 and 190 kDa. No reactivity with the 230-kDa bullous pemphigoid antigen and the 250-kDa desmoplakin I antigen was found. PMID- 8494757 TI - Epidermolysis bullosa junctionalis progressiva in three siblings. AB - Three siblings of Swiss origin with epidermolysis bullosa junctionalis progressiva are described. The following clinical features were present from school age: dystrophy of the nails, non-scarring blistering of the skin, mild skin atrophy, hypodontia and dental caries. Light microscopy showed subepidermal blistering. Direct immunofluorescence was negative. On indirect immunofluorescence staining of a fresh spontaneous blister, bullous pemphigoid antigen and laminin were localized to the blister roof, and collagen IV and collagen VII to the blister base, indicating junctional splitting. Electron microscopy revealed a normal dermo-epidermal junction zone, including normal hemidesmosomes. There were no deposits of electron-dense amorphous material. PMID- 8494758 TI - Combined treatment of solar urticaria with plasmapheresis and PUVA. PMID- 8494759 TI - Radiation-induced squamous carcinoma arising within a seborrhoeic keratosis. AB - Seborrhoeic keratoses (SK) are common skin tumours. They are benign, and present little difficulty in management. However, rare malignant transformation is recognized. We report a case of a squamous cell carcinoma arising from dysplastic changes within a long-standing SK on the chest wall of a 75-year-old retired radiologist, and consider the role of radiation in inducing malignant change within SKs. PMID- 8494760 TI - Subcutaneous changes in dermatomyositis. AB - We report the case of a 42-year-old woman with concomitant panniculitis and dermatomyositis. Painful, indurated lesions on the buttocks, thighs, arms, abdomen and breasts were associated with proximal muscle weakness. Skin biopsy revealed lobular panniculitis, and vacuolar degeneration of epidermal basal cells. Direct immunofluorescence was negative. Serum muscle enzyme (creatinine phosphokinase) levels were elevated, and electromyography demonstrated a myositic process. Muscle biopsy showed an inflammatory myositis. These results were consistent with dermatomyositis associated with panniculitis. Only five cases of this association have been reported previously. The relationship between these two conditions is discussed. PMID- 8494761 TI - Tufted hair folliculitis. A study of four cases. PMID- 8494762 TI - Ehlers-Danlos syndrome type VIII: biochemical, stereological and immunocytochemical studies on dermis from a child with clinical signs of Ehlers Danlos syndrome and a family history of premature loss of permanent teeth. AB - We studied collagen expressed by skin fibroblasts in culture, and performed immunocytochemical, ultrastructural and stereological analysis of dermis from a child with signs reminiscent of a mild Ehlers-Danlos syndrome (EDS) type IV and severe periodontitis. No alterations in types I and III [corrected] collagen synthesis and secretion, or serum levels of type III procollagen aminoterminal propeptide were found, and morphological studies revealed non-specific alterations of collagen and elastic components observed in many connective tissue disorders. PMID- 8494763 TI - An early drawing of Blaschko's lines. PMID- 8494764 TI - Spontaneous bruising during treatment with isotretinoin. PMID- 8494765 TI - Asymmetrical scabies burrows in a hemiplegic patient. PMID- 8494766 TI - Exacerbation of psoriasis with GM-CSF therapy. PMID- 8494767 TI - Leucocytoclastic vasculitis in subacute cutaneous lupus erythematosus. PMID- 8494768 TI - CNS midline enhancers of the Drosophila slit and Toll genes. AB - The Drosophila CNS midline cells comprise a small, well-characterized group of neurons and glia in which the transcriptional control of CNS development can be studied. Using germ-line transformation of lacZ fusion constructs, we have dissected putative regulatory regions of the slit and Toll genes to identify CNS midline-restricted transcriptional enhancers. This analysis has uncovered DNA regions able to drive lacZ expression in most tissues in which embryonic slit and Toll are expressed, including three separable CNS midline-conferring regions: one in the Toll gene which is expressed early in all of the CNS midline precursors, and two in the slit gene which are expressed later in the midline glia (MG). PMID- 8494769 TI - Skin cancer in the engineering industry from the use of mineral oil. 1949. PMID- 8494770 TI - An epidemiological study of workers potentially exposed to ethylene oxide. AB - This epidemiological study was of 18,728 employees at 14 United States facilities producing sterilised medical supplies and spices, who were potentially exposed to ethylene oxide (EO) for at least 90 days. The mortality of the cohort was studied to the end of 1988. A total of 1353 deaths was identified. The cohort had a significantly lower mortality than the general population from all causes, all cancers, and non-malignant diseases. In the entire cohort, mortality was not significantly increased from any of the cancer sites examined. In particular, no significant increase in mortality was found in the cancer sites of interest based on previous studies--namely, stomach, leukaemia (including major specific cell types), pancreas, and brain. The lack of an increased mortality for these cancer sites was further strengthened by the lack of a dose-response relation with duration of employment and latency. Among the men, a statistically significant increase in mortality from non-Hodgkin's lymphoma was found. There was no indication for a dose-response relation for non-Hodgkin's lymphoma and no specific job categories seemed to be responsible for the increase. Among the women, a deficit of non-Hodgkin's lymphoma was found, which was not consistent with the finding in the men. Therefore, the increase among the men did not seem to be related to exposure to EO. PMID- 8494771 TI - Cancer mortality in ethylene oxide workers. AB - A cohort of 1971 chemical workers licensed to handle ethylene oxide was followed up retrospectively from 1940 to 1984 and the vital status of each subject was ascertained. No quantitative information on exposure was available and therefore cohort members were considered as presumably exposed to ethylene oxide. The cohort comprised 637 subjects allowed to handle only ethylene oxide and 1334 subjects who obtained a licence valid for ethylene oxide as well as other toxic gases. Potential confounding arising from the exposure to these other chemical agents was taken into consideration. Causes of death were found from death certificates and comparisons of mortality were made with the general population of the region where cohort members were resident. Seventy six deaths were reported whereas 98.8 were expected; the difference was statistically significant. The number of malignancies for any site exceeded the expected number (standardised mortality ratio (SMR) = 130; 43 observed deaths; 95% confidence interval (95% CI) 94-175) and approached statistical significance. For all considered cancer sites the SMRs were higher than 100 but the excess was only significant (p < 0.05, two sided test) for lymphosarcoma and reticulosarcoma (International Classification of Diseases--9th revision (ICD-9) = 200; SMR = 682; four observed deaths; 95% CI 186-1745). The excess of cases for all cancers of haematopoietic tissue (ICD-9 = 200-208) also approached statistical significance (SMR = 250; six observed deaths; 95% CI 91-544). Focusing the analysis on the subcohort of the ethylene oxide only licensed workers, who are likely to have experienced a more severe exposure to this gas, it became evident that all but one of the observed cases of haematopoietic tissue cancers in the cohort were confined to this subgroup, enhancing the relevant SMR to 700 (95% CI 237-1637) and the SMR of lymphosarcoma and reticulosarcoma to 1693 (95% CI 349-4953). PMID- 8494772 TI - Evoked potentials and cerebral blood flow in solvent induced psycho-organic syndrome. AB - Epidemiological studies have provided evidence that neuropsychiatric symptoms are induced by long term exposure to solvents; individual diagnosis with psychometric tests, however, is not always possible (for example, when the patient has linguistic difficulties). Therefore evoked potentials and cerebral blood flow were studied in 50 patients occupationally exposed to solvents who were referred to our department and for whom a solvent induced psycho-organic syndrome was suspected. Degree of exposure was evaluated by its duration (mean 13.9, range 1 to 37 years) and its intensity (from an interview). At the group level, P22 and N35 latencies and amplitude N20-P22 of somatosensory evoked potentials were higher in cases than in controls (p < 0.05), whereas there was no difference for brainstem and visual evoked potentials, nor for hemispheric cerebral blood flow (but a higher distribution in the left occipital region was seen in patients, p < 0.05). Some parameters were linked to degree of exposure (amplitude N20-P22 of somatosensory evoked potentials, interpeak latency I-V of brainstem evoked potentials, distribution of cerebral blood flow in the internal frontal left region). At the individual level, these examinations were not of diagnostic value because sensitivity was low. PMID- 8494773 TI - Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers. AB - An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver. PMID- 8494774 TI - A review of potential human carcinogenicity of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP. AB - For the purpose of assessing the human carcinogenic potential of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP, the relevant epidemiological and toxicological evidence is reviewed. These compounds have not produced tumours in animal studies conducted under current test guidelines, giving no reason to predict that they would be carcinogenic to humans. Epidemiological studies have been conducted on three continents; greater emphasis is placed on the studies reported from western Europe, however, as this has been the area of more use. Although several of these studies provide suggestive evidence of associations between exposure to chlorophenoxy compounds and increased risks for some uncommon cancers, it is inconsistent and far from conclusive. None of the evidence specifically implicates MCPA, MCPP, or 2,4-DP as human carcinogens. PMID- 8494775 TI - Risk factors for kidney cancer in New South Wales. IV. Occupation. AB - In a population based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP), and 523 controls from the electoral roles were obtained about employment in certain industries or occupations, and exposure to particular chemicals chosen because of suspected associations with kidney cancer. A low level of education increased the risk for CaRP but not RCC. After adjustment for known risk factors, exposure to asbestos significantly increased the risk for RCC (relative risk (RR) = 1.62; 95% confidence interval (95% CI) 1.04-2.53). Working in the dry cleaning industry had a stronger link with CaRP (RR = 4.68; 95% CI 1.32-16.56) than with RCC (RR = 2.49; 95% CI 0.97-6.35). Working in the iron and steel industry doubled the risk for CaRP (RR = 2.13; 95% CI 1.04-4.39) whereas employment in the petroleum refining industry had a non significant association with CaRP (RR = 2.60; 95% CI 0.88-7.63) and none with RCC. PMID- 8494776 TI - Temporary threshold shifts in fingertip vibratory sensation from hand-transmitted vibration and repetitive shock. AB - Temporary threshold shifts (TTSs) in vibrotactile perception produced by continuous vibration and repetitive shock have been investigated. Subjects were exposed to vertical hand-transmitted 100 Hz continuous vibration and various repetitive shocks of equal energy content formed from one complete cycle of a 100 Hz sine wave. The repetition rate of the cycles was 5, 25, 50, or 100 s-1 while the root-mean-square (rms) acceleration measured over exposures of five minutes was held constant at 2.5, 5, or 10 ms-2 rms (weighted according to British Standard (BS) 6842 and International Standard (ISO) 5349). A control condition with no vibration was also included. Subjects held a handle with 10% of their maximum hand grip force. When exposed to five shocks per second at each of the three frequency-weighted acceleration magnitudes the subjects developed a small TTS. Exposure to 100 shocks per second (continuous vibration) at each of the three frequency-weighted acceleration magnitudes caused a large TTS, although the total frequency-weighted energy was the same as when exposed to five shocks per second. The relation between the TTS, the logarithm of the shock repetition rate, and the logarithm of the frequency-weighted rms acceleration was described by the relation TTS = -16.256 + 11.812 log10 R + 15.179 log10 ahw, where TTS is the temporary threshold shift, R is the shock repetition rate, and ahw is the frequency-weighted rms acceleration according to BS 6842 and ISO 5349. The results suggest that the equal energy hypothesis underlying BS 6842 and ISO 5349 is inappropriate for the prediction of the TTS produced by repetitive shocks. PMID- 8494777 TI - Neuropsychological performance and solvent exposure among car body repair shop workers. AB - A cross sectional study to evaluate symptom reporting and neuropsychological test performance among a cohort of car body repair workers (n = 124) was performed using a computer-administered test system. Subjects with high and medium current exposures to solvent and paint (n = 39 and 32), and low exposure subjects who formerly painted (n = 29) reported significantly more acute and chronic neurological symptoms than did low exposure subjects with no history of painting (n = 24). Subjects with higher current exposure performed significantly less well on selected tests of visual perception and memory, but there were no significant exposure related differences in mood state, motor speed, or visuomotor performance. The exposure related effects were most noticeable among subjects 35 years or older. The findings are consistent with age interactive central neurotoxic effects of current exposure to solvents or of cumulative past exposure, although the study is unable to distinguish between these possibilities. The computer administered test system was effective in this field based investigation involving multiple, geographically dispersed worksites. PMID- 8494778 TI - Haemolysis of human erythrocytes by pentachlorophenol and its suppression by albumin. PMID- 8494779 TI - A potential cause of bladder cancer. PMID- 8494780 TI - Pulmonary effects of exposure to fine fiberglass: irregular opacities and small airways obstruction. PMID- 8494781 TI - Loss of the G1-S control of cyclin A expression during tumoral progression of Chinese hamster lung fibroblasts. AB - The expression of cyclin A, one of the key regulators of cell cycle progression in association with cdc2/cdk2 protein kinases and which undergoes cyclic accumulation during the cell cycle, has been investigated in CCL39 Chinese hamster lung fibroblasts and in two transformed variants, A71 and 39Py. Whereas A71 (selected after tumor induction in nude mice) is subject to growth arrest (less than 5% of labeled nuclei after 24 h of serum starvation), 39Py (obtained after transformation by polyoma virus) is not (more than 50% of labeled nuclei). In both cells, cyclin A expression was correlated with establishment of S phase, with a progressive deregulation of its G1 controls. This deregulation was not detected with the two early response genes c-fos and c-myc. The kinetics of accumulation of cyclin A lagged behind that of [3H]thymidine incorporation, thereby questioning a direct role for cyclin A in S phase triggering. Moreover, transforming growth factor beta 1, which is known to inhibit alpha-thrombin or fibroblast growth factor-induced mitogenicity in G0-arrested CCL39 cells, is shown here to down-regulate cyclin A expression in both CCL39 and A71 cells but has no effect on 39Py cells. These data establish cyclin A as a sensitive marker for the loss of growth factor requirement. PMID- 8494782 TI - Repression of autocrine transforming growth factor beta 1 and beta 2 in quiescent CBS colon carcinoma cells leads to progression of tumorigenic properties. AB - Previous work has shown that repression of negative autocrine transforming growth factor (TGF) beta 1 did not alter the growth rate of a human colon carcinoma cell line, but the time required for the cells to enter exponential growth from lag phase was reduced (S. P. Wu, D. Theodorescu, R. Kerbel, J. K. V. Willson, K. M. Mulder, L. E. Humphrey, and M. G. Brattain, J. Cell Biol., 116: 187-196, 1992). These results have led to the hypothesis that the tumor suppressive activity of autocrine TGF-beta 1 was directed at quiescent nondividing cells rather than actively dividing cells. In order to test this hypothesis, a weakly tumorigenic, well-differentiated human colon carcinoma cell line designated CBS, which expressed autocrine TGF-beta 1 and -beta 2 activity in quiescent cells, but not in exponential growth phase cells, was identified. This cell line was stably transfected with a full-length TGF-beta 1 antisense complementary DNA. Constitutive expression of TGF-beta 1 antisense mRNA in CBS cells resulted in repression of autocrine TGF-beta 1 and -beta 2 protein activity in quiescent cells of approximately 10-fold. TGF-beta 2 repression could have been due to interaction with TGF-beta 1 antisense mRNA, since these two isoforms have a high degree of homology, or it could have been indirectly due to TGF-beta 1 repression, since this isoform has been shown to affect transcriptional and posttranscriptional control of TGF-beta 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494783 TI - Induction of pre-B lymphoid leukemia following reconstitution of lethally irradiated mice with v-erb-B virus-infected bone marrow progenitor cells. AB - We have previously shown that v-erb-B contained within a recombinant murine retroviral vector is capable of transforming pre-B lymphocytes (M. Miller, A. K. Kennewell, and G. Symonds, Leukemia, 6: 18-28, 1992) and early erythroid precursor cells [blast-forming units (erythroid) (M. Miller, A. Kennewell, Y. Takayama, A. Bruskin, J. M. Bishop, G. Johnson, and G. Symonds, Oncogene, 5: 1125 1131, 1990)] in vitro. To determine the sites and nature of v-erb-B-induced transformation in vivo, the hematopoietic systems of lethally irradiated mice were repopulated with v-erb-B-infected bone marrow. All mice became moribund within 4-12 weeks of reconstitution, with a median onset of disease at 6 weeks. Histopathological and flow cytometric evaluation of tissues from diseased mice, as well as morphological and phenotypic analysis (cytochemical as well as molecular) of the cell lines established from the mice, revealed that all but one of the mice examined at postmortem had developed a pre-B lymphoid leukemia or lymphoma. Abnormally high levels of mast cells in the spleen and bone marrow of the remaining mouse indicated a mast cell disease. The development of pre-B lymphoid malignancy in the majority of the reconstituted mice indicates a marked predisposition of v-erb-B to transform cells of the pre-B lymphoid lineage. The reconstitution of lethally irradiated mice with v-erb-B virus-infected bone marrow provides a model system for the analysis of events involved in the initiation and maintenance of acute lymphoid leukemia. PMID- 8494784 TI - c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif. AB - c-Myc and wild-type p53 have been shown to play important roles in the regulation of cellular proliferation and oncogenic transformation. We have previously shown that the p53 promoter contains a conserved consensus recognition sequence for the basic-helix-loop-helix-containing proteins, identical to the specific binding site for c-Myc/Max heterodimers. Here, we demonstrate that this element, which is required for full promoter activity, is bound by in vitro translated c-Myc/Max heterodimers. Furthermore, we found that in cotransfection assays, c-Myc trans activates the p53 promoter as well as a hybrid herpes simplex virus-thymidine kinase promoter containing multiple copies of a synthetic p53-derived c-Myc binding site. The p53 promoter deleted of the basic-helix-loop-helix consensus recognition sequence is not trans-activated by c-Myc, thus suggesting that c-Myc trans-activates the p53 promoter through the basic-helix-loop-helix recognition motif. These findings raise the possibility that the p53 gene may be a potential target for trans-activation by c-Myc in vivo. PMID- 8494785 TI - Transgenic mouse model of X-linked cleft palate. AB - A transgenic mouse line, PyLMP.5, exhibited a sex-linked lethality not observed in any other lines expressing the transgene. In this unique line, the transgene integrated into the X chromosome, yielding a simple tandem duplication of the insert sequences with minimal, if any, additional rearrangement of the cellular sequences. The predominant phenotype was a cleft secondary palate and neonatal lethality in males. Survival of females was dependent on the mouse strain background. The disrupted cellular sequences have been mapped to the proximal region of the mouse X chromosome. The disrupted locus may represent the mouse counterpart to a human locus mutated in an X-linked cleft secondary palate syndrome. PMID- 8494786 TI - The TRK and RET tyrosine kinase oncogenes cooperate with ras in the neoplastic transformation of a rat thyroid epithelial cell line. AB - We have recently reported that about 50% of papillary thyroid carcinomas harbor an activated TRK or RET oncogene. Two retroviral vectors containing the activated TRK or RET/PTC oncogene have been used to infect a differentiated rat thyroid epithelial cell line, namely the PC Clone 3 cell line. Upon infection with the TRK virus, the PC Clone 3 cells lost only the ability to trap iodide and to express the thyroperoxidase gene. Conversely, when infected with the PTC virus, the PC Clone 3 cells completely lost all of their differentiated functions. However, both the PC-TRK and PC-PTC cell lines were unable to grow in soft agar, and they were not tumorigenic when injected into nude mice. A completely undifferentiated and malignant phenotype was obtained by the cooperation between the TRK or RET and the viral Ha-ras or Ki-ras oncogenes. PMID- 8494787 TI - Expression of two distinct homologues of Xenopus Max during early development. AB - The Max protein belongs to the basic region-helix-loop-helix-leucine zipper family of transcriptional regulators. Max heterodimerizes with Myc family proteins to form sequence-specific DNA-binding complexes. In order to elucidate the potential role of Myc and Max during amphibian embryogenesis, we have isolated and analyzed the expression of two Xenopus Max complementary DNAs: XMax1 and XMax2. Comparison of XMax1 and XMax2 with their mammalian counterparts demonstrates a strikingly high degree of conservation at both the nucleotide and amino acid levels, with the exception of a 24-residue deletion in both XMax proteins within their COOH termini. In addition, the two Xenopus Max proteins differ in that XMax2 contains a unique 27-amino acid insertion that interrupts the COOH-terminal end of the zipper domain; XMax1 lacks this insertion. Despite these differences, both XMax1 and XMax2 can form complexes with either Xenopus or human c-Myc proteins. Analysis of XMax expression during embryogenesis reveals that both mRNA and protein are expressed throughout early development, including the egg, 32-cell stage, and midblastula transition. Although the expression of XMax1 RNA appears to predominate at all stages examined, the ratios of XMax1 to XMax2 protein vary during development as well as between different tissue culture cell lines, suggesting a potential for cell type-specific regulation. Our results demonstrate the presence of Xenopus Max throughout frog development, raising the possibility that Myc and Max could function as a complex even during early embryogenesis. PMID- 8494788 TI - Effects of c-myc expression on proliferation, quiescence, and the G0 to G1 transition in nontransformed cells. AB - The relative contributions of deregulation versus high level expression of the c myc gene to malignant transformation are not clear. To investigate the effects of subtle perturbations in c-myc expression on normal cellular physiology, we isolated cell lines with one c-myc gene copy disrupted by targeted homologous recombination. The heterozygous cell lines were further modified by introducing a c-myc transgene expressed 4-fold above the normal diploid level. During exponential growth, heterozygous cells expressed c-Myc mRNA at approximately 50% of the level found in diploid cells, resulting in a slower growth rate. The c-myc transgene reversed the growth defect and accelerated growth relative to diploid cells. Serum deprivation of transgene-expressing cells caused a fraction of the culture to undergo apoptosis. After an initial wave of apoptosis, the remainder of the culture successfully entered Go. Transgene mRNA continued to be constitutively expressed in quiescent cells, but c-Myc protein was not detectable. During the G0 to G1 transition, heterozygous cells induced c-myc expression with normal kinetics, but levels throughout the time course were consistently at least 50% lower than those in diploid cells. The reduction in c myc expression was correlated with a 3-4-h delay in entry into S phase. The presence of the transgene, which was expressed constitutively throughout the G0 to G1 transition, reversed the delay but did not further accelerate entry into S phase. Our results show that even small perturbations in c-myc expression cause changes in the proliferative status of cells and thus argue that the natural regulation patterns of the gene are crucial for the maintenance of normal cellular physiology. PMID- 8494789 TI - Protein tyrosine phosphatase 1B undergoes mitosis-specific phosphorylation on serine. AB - We have investigated the regulation of protein tyrosine phosphatase 1B (PTP1B) through the cell cycle of HeLa cells. PTP1B from HeLa cells arrested in mitosis migrated more slowly during sodium dodecyl sulfate-polyacrylamide gel electrophoresis than did PTP1B from unsynchronized HeLa cells. To explore whether this mobility shift was caused by phosphorylation, PTP1B was immunoprecipitated from 32Pi-labeled unsynchronized and mitotic HeLa cells. PTP1B from mitotic cells incorporated significantly more 32Pi than did PTP1B from unsynchronized cells. Alkaline phosphatase treatment of mitotic HeLa cell lysates resulted in the conversion of PTP1B to its more rapidly migrating form, confirming that the mobility shift was a result of the mitotic phosphorylation. Phosphoamino acid analysis of PTP1B from mitotic cells revealed that PTP1B became phosphorylated on serine. Dephosphorylation of PTP1B occurred following the release of cells from nocodazole synchronization and was independent of new protein synthesis. This dephosphorylation was inhibited by okadaic acid, a potent inhibitor of types 1 and 2A serine/threonine phosphatases. The mitotic phosphorylation had no apparent effect on the activity of PTP1B as measured in in vitro phosphatase assays using 32P-labeled Raytide as substrate. p34cdc2 appears not to be the mitotic PTP1B kinase, as mapping experiments showed that this enzyme phosphorylated PTP1B on a site different from that on which it was phosphorylated in vivo. These observations suggest that PTP1B may be differentially regulated through the cell cycle. PMID- 8494790 TI - Spatiotemporal expression of two cell-cell adhesion molecule 105 isoforms during liver development. AB - The rat liver adhesion molecule cell CAM 105 has been postulated to be involved in liver histogenesis. Recently, it was shown to exist in two isoforms that differ in the length of their cytoplasmic domains (O. Culic, Q-H. Huang, D. Flanagan, D. C. Hixson, and S. H. Lin, Biochem. J., 285: 47-53, 1992). Isoform specific differences in phosphorylation and aggregation function have been observed. To study the possible roles of these isoforms during liver development, we have used both complementary DNA probes and isoform-specific antibodies to examine their temporal and spatial expression. Northern blot analysis revealed low steady-state levels of a 4.0-kilobase RNA at 15-20 days gestation, which increased dramatically at birth and remained at least 12-fold higher than fetal levels in neonatal and adult liver. Additional polyadenylated RNA species of 6.0 and 2.9 kilobases were detected after birth. Steady-state levels of cell CAM 105 RNA in cultured adult and fetal hepatocytes were comparable to in vivo levels, respectively, and were not influenced by treatment with transforming growth factor beta or by culture density. Increases in cell CAM 105 protein demonstrated by immunoblot analysis correlated with the RNA increases, suggesting that regulation of cell CAM 105 expression is largely transcriptional during development. Ratios of the long and short isoforms remained relatively constant after birth. Isoform-specific antipeptide antibodies localized both isoforms primarily to maturing bile canalicular domains of hepatocytes during liver development. The long isoform could not be detected in fetal liver in situ prior to 20 days, however, suggesting that specific roles may exist for these molecules during development. PMID- 8494791 TI - GC factor represses transcription of several growth factor/receptor genes and causes growth inhibition of human gastric carcinoma cell lines. AB - The GC factor (GCF) binds to specific GC-rich sequences in the epidermal growth factor receptor (EGFR) gene promoter and represses its transcription. In this study, by the use of GCF transfection, we examined whether GCF represses the gene expression of several other growth factors and receptors and causes growth inhibition of cancer cells. The transfection of GCF expression vector into gastric carcinoma cell lines (TMK-1 and MKN-28) decreased the mRNA levels of transforming growth factor (TGF) alpha, insulin-like growth factor II, and c-met. The reduction of TGF-alpha expression was confirmed at the protein level by enzyme-linked immunosorbent assay. Transfection of GCF expression vector interfered with the mRNA accumulation for EGFR and TGF-beta induced by epidermal growth factor in gastric carcinoma cell lines. The carcinoma cells transfected with GCF expression vector did not grow in a serum-free medium, whereas the control cells did grow under serum-free conditions. When the growth of the gastric carcinoma cell lines was studied in nude mice, GCF-transfected carcinoma cells showed a significantly slower growth compared to the control tumor. Transient cotransfection analysis with NIH3T3 cells revealed that GCF repressed the promoter activity of TGF-alpha in addition to EGFR. These findings indicate that GCF negatively regulates gene expression of not only the EGFR but also several other growth factor and receptor genes and can inhibit the growth of gastric carcinomas in immunodeficient mice. PMID- 8494792 TI - Developmental expression of the vav protooncogene. AB - We have examined the expression of the vav protooncogene during mouse embryogenesis using RNase protection assays, in situ hybridization, and immunocytochemical analysis. vav gene transcripts were first detected in E11.5 embryos in the blood-forming islands and megakaryocytes of the fetal liver. During diversification of hematopoietic activity in the embryo, vav gene expression became down-regulated in the liver and activated in thymus and spleen. In newborn animals, vav expression was also confined to hematopoietic tissues, with the exception of the ameloblastic cell layer at the latest stages of tooth morphogenesis. In the adult, vav transcripts were found in spleen, thymus, lymph nodes, and bone marrow, but not in liver. In spleen, vav transcripts were concentrated in the white pulp areas, whereas in the red pulp, the vav transcripts appeared to be primarily localized in the megakaryocytes. In thymus, vav expression was found to be more abundant in the cortical areas than in the medulla. In agreement with these observations, purified thymic lymphocytes showed heterogeneous immunoreactivity against the Vav protein, whereas splenic lymphocytes and bone marrow-derived cells displayed rather uniform levels of expression. These observations suggest that the vav protooncogene plays an important role in the signal transduction pathways that regulate the development and maintenance of the hematopoietic system. PMID- 8494793 TI - Effect of alpha-protein kinase C neutralizing antibodies and the pseudosubstrate peptide on phosphorylation, migration, and growth of REF52 cells. AB - REF52 cells are a line of rat embryo fibroblasts that express alpha-, delta-, epsilon-, and zeta-protein kinase Cs (PKCs). In this report, we have used neutralizing antibodies to alpha-PKC to study the role of this specific PKC isozyme in REF52 cell functions. Effects of the more general PKC inhibitor, the pseudosubstrate peptide, were also studied. Previous work demonstrated that alpha PKC is concentrated in focal contacts of REF52 cells (Jaken, S., Leach, K., and Klauck, T. J. Cell Biol., 109: 697-704, 1989). alpha-PKC redistributed to the leading lamellopodia of cells stimulated to migrate into an artificial wound, indicating that alpha-PKC activation may be coupled to migratory stimuli. The effects of the alpha-PKC neutralizing antibodies and the pseudosubstrate peptide on responses associated with focal contact functions, namely attachment, migration, and growth, were studied. The data demonstrate that the antibodies and the pseudosubstrate peptide were all efficient inhibitors of phorbol ester stimulated phosphorylation. However, only the pseudosubstrate peptide efficiently inhibited the migration and growth responses necessary to repopulate an artificial wound. These results indicate that PKCs, but probably not alpha-PKC in particular, are important in these responses. However, because the neutralizing antibodies did not completely inhibit phorbol 12,13-dibutyrate-stimulated phosphorylation, a potential role for alpha-PKC in migration and growth cannot be excluded. PMID- 8494794 TI - Induction of markers of normal differentiation in human colon carcinoma cells by the v-rasH oncogene. AB - The molecular events that regulate differentiation of human colon mucosal cells are not known. Although a number of in vitro models to study this question exist, none have identified a gene product which could function as a mediator of cell differentiation. Although the Ki-ras gene is frequently mutated in human colon cancer, the Ha-ras protooncogene is maximally expressed in the most differentiated cells of intestinal mucosa. In order to study the effects of Ha ras gene overexpression on the differentiation phenotype in human colon cancer cells, we have expressed the v-rasH oncogene in CaCO2 cells. This maneuver resulted in a marked induction of gene expression of multiple markers characteristic of intestinal brush border differentiation. These include a > or = 30-fold induction of sucrase, a 10-fold increase in intestinal alkaline phosphatase, a 20-fold induction of transforming growth factor alpha, and a 5 fold increase in transforming growth factor beta 1 steady-state mRNA levels. Finally, the CaCO2-ras cells undergo a > or = 95% reduction in DNA synthesis under serum-deficient conditions and cannot be restimulated after such treatment, suggesting terminal differentiation, whereas the same treatment has no effect on the proliferative capacity of the parent CaCO2 cell line. These studies with CaCO2 human colon cancer cells provide a model to study the role of v-rasH and related genes in colon epithelial differentiation. PMID- 8494795 TI - The morphology of collicular and retinal axons ending on small relay (W-like) cells of the primate lateral geniculate nucleus. AB - The lateral geniculate nucleus (LGN) of every primate examined contains a set of small relay cells in addition to separate sets of magnocellular and parvocellular relay cells. These small cells receive a direct retinal projection, and an indirect retinal projection via the superior colliculus (SC). Receptive-field analyses of the small LGN cells in the bush baby, a lorisiform primate, indicate that this cell class is composed of subclasses, similar in physiology to cat W cells. In an effort to identify some of these subclasses, we have examined the morphological features of retinal and collicular axonal arbors that end on small W-like cells in the LGN of the bush baby, Galago crassicaudatus. Small cells in this species are found in a prominent pair of koniocellular (K) layers as well as the interlaminar zones (ILZs). Retinal arbors were examined by bulk iontophoretic injection of horseradish peroxidase into the optic tract. Collicular arbors were filled via iontophoretic injection of biocytin into the superficial layers of the SC. Forty-eight axon arbors were completely reconstructed and quantitatively evaluated. Our findings show that retinal and collicular axon terminals differ in morphology on the basis of a number of criteria. Our analyses also suggest that retinal axons may have a stronger influence on K cells and collicular axons have a stronger influence of ILZ cells. The ramifications of these findings are provocative since these small LGN cells are known to project directly to the cytochrome-oxidase (CO) blobs within striate cortex. This relationship suggests that CO blob cells receive complex visual input not only from magnocellular and parvocellular LGN cells, but also from small cell pathways that are differentially influenced by retinal and collicular cells. PMID- 8494796 TI - Nucleus isthmi in goldfish: in vitro recordings and fiber connections revealed by HRP injections. AB - Recordings of field potentials in nucleus isthmi (NI) were obtained in an in vitro preparation of goldfish brain using a lateral approach. Horseradish peroxidase (HRP) was injected from recording electrodes to verify recordings within the nucleus and to label axonal pathways and cell bodies. Activity in NI was repetitive and could be elicited by stimulation of the optic nerve, tectum, pretectum, or tectobulbar tract. Spontaneous activity was present in some preparations and consisted of bursts with intervening silent periods. Anatomical and electrophysiological evidence indicated that the primary isthmotectal pathway is composed of fine fibers that exit NI rostrally and pass through pretectum to enter tectum rostrally. An afferent pathway consisting of both fine- and large diameter fibers entered NI ventromedially; the large diameter axons have been previously reported in percomorph fishes, but were not thought to be present in cyprinids such as goldfish. The large diameter axons arise from labeled cell bodies in the region of the lateral thalamic nucleus. No labeled cell bodies were seen in ipsilateral nucleus pretectalis superficialis, pars magnocellularis, where they are seen in percomorphs. The fine axons, which have not been reported in percomorph fishes, were shown to arise from tectal bipolar (type VI) neurons. As in percomorphs, tectal type XIV neurons were also labeled. This and corroborating recordings from nucleus isthmi constitute the fist demonstration of a tectoisthmic projection in a cyprinid fish. PMID- 8494797 TI - A comparison of the 40-Hz response in man, and the properties of macaque ganglion cells. AB - Visually evoked field potentials in human subjects and single-cell responses from retinal ganglion cells in the macaque monkey were compared in closely similar stimulus situations. The classical heterochromatic flicker photometry (HFP) technique was used to measure spectral sensitivity in man, both psychophysically and by recording the 40-Hz response, and to measure the spectral sensitivity of magnocellular (MC-) pathway cells of the macaque. The three measures gave closely similar spectral-sensitivity curves. Close agreement between the three measures was also found when the variable-modulation HFP technique was used to measure spectral sensitivity. When the relative phase between red and green lights was varied, the point of minimum subjective flicker for human observers was close to a sharp minimum found in the amplitude of the 40-Hz response in human and was also close to a minimum in the response of MC-pathway neurons in the monkey. The human 40-Hz response saturated at between 10 and 30% modulation depth, and so did the response of MC-pathway cells in the monkey. The 16-Hz response in human showed none of the above correlations with MC-pathway properties. On the other hand, parvocellular (PC-) pathway cells responded vigorously to constant luminance, chromatic modulation, at frequencies higher than can be detected by human observers. The human 16-Hz response also was strong in that stimulus situation. In addition, the response of PC-pathway cells on increasing modulation depth showed little saturation, and this behaviour was paralleled by the human 16 Hz response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494798 TI - Apomorphine blocks form-deprivation myopia in chickens by a dopamine D2-receptor mechanism acting in retina or pigmented epithelium. AB - Studies of form-deprivation myopia (FDM) in animal models have shown that postnatal ocular growth is regulated by the quality of patterned images on the retina. One of the major challenges in myopia research is to identify the biochemical mechanisms which translate retinal visual responses into signals that regulate scleral growth. Dopamine (DA) has been implicated in this process, since retinal DA levels decline in FDM and subconjunctival injections of apomorphine (Apo, a nonspecific DA agonist) prevent FDM in a dose-dependent way (Stone et al., 1989). To gain insight into where and how DA ligands act to regulate ocular elongation, we compared the action and distribution of DA receptor ligands injected intravitreally vs. subconjunctivally in young chicks. Ocular length was measured by A-scan ultrasound. We found that daily intravitreal injections of Apo block FDM at a 50% effective dose (ED50) of 5 pg per day, or a peak concentration in the vitreous humor of 108 pM, compared to an ED50 of 2.5 ng for subconjunctival injections as reported by Stone et al. (1989, 1990). [3H] spiperone, a D2-receptor antagonist, reached average maximum retinal concentrations of 160 pM and 260 pM, during the first hour after intravitreal and subconjunctival administration, respectively, at the ED50 dose. In contrast, the maximum spiperone concentrations in the retinal pigment epithelium (RPE) were 30 pM and 410 pM, respectively, after intravitreal or subconjunctival ED50 doses. Spiperone concentrations in sclera after ED50 doses to the two sites differed by 4 x 10(4) (0.4 pM vs. 1.7 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494799 TI - Synaptic microcircuitry of bipolar and amacrine cells with serotonin-like immunoreactivity in the retina of the turtle, Pseudemys scripta elegans. AB - Although serotonin is thought to be a neurotransmitter in a number of retinal systems, much of the precise synaptic connectivity of serotonergic neurons is unknown. To address this issue, we used an antiserum directed against serotonin to label serotonergic bipolar and amacrine cells in the turtle retina. Light microscopic analysis of labeled amacrine and bipolar cells indicated that both had bistratified dendritic arborizations primarily in stratum 1 and in strata 4/5 of the inner plexiform layer. Ultrastructural analysis of the neurocircuitry of these cells indicated that the processes of labeled bipolar cells in the outer plexiform layer made basal junction contacts with photoreceptor terminals. Only in rare instances did labeled bipolar cells processes invaginate near photoreceptor ribbon synapses. Processes of labeled bipolar cells received both conventional and small ribbon synaptic contacts in the outer plexiform layer. Bipolar cell processes in stratum 1 of the inner plexiform layer synapsed onto either amacrine/amacrine or amacrine/ganglion cell dyads, and made rare ribbon synaptic contacts onto labeled amacrine cell processes. Synaptic inputs to serotonergic bipolar cells in stratum 1 were from unlabeled bipolar and amacrine cells. Bipolar cell contacts in strata 4/5 were similar to those in stratum 1, but were fewer in number and no bipolar cell inputs were seen. Labeled amacrine cell output in both strata was onto other unlabeled amacrine cells and ganglion cells; but synaptic outputs to unlabeled bipolar cells were only seen in strata 4/5. In both strata 1 and 4/5, synaptic inputs to labeled amacrine cells were from both unlabeled amacrine cells and labeled bipolar cells. The serotonergic amacrine cells had many more synaptic interactions in stratum 1 than in strata 4/5 which supports the role of serotonergic bipolar cells in the OFF pathway of retinal processing. Interactions between serotonergic bipolar and amacrine cells may play an important role in visual processing. PMID- 8494800 TI - Development of the rabbit retina, III: Differential retinal growth, and density of projection neurons and interneurons. AB - To provide a quantitative description of postnatal retinal expansion in rabbits, a new procedure was developed to map the retinae, which cover the inner surface of hemispheres or parts of rotation ellipsoids, in situ, onto a single plane. This method, as well as the known distribution of Muller cells per unit retinal surface area, were used to estimate the redistribution of specific subpopulations of Muller cells within different topographic regions of the retinae. Muller cells are known to exist as a stable population of cells 1 week after birth and can therefore be used as "markers" for determining tissue expansion. Our results show that differential retinal expansion occurs during development. Peripheral retinal regions expand at least twice as much as the central ones. Furthermore, there is a greater vertical than horizontal expansion. This differential retinal expansion leads to a corresponding redistribution of 5-hydroxytryptamine (5-HT) accumulating amacrine cells. Differential retinal expansion, however, does not account for all of the changes in the centro-peripheral density gradient of cells in the ganglion cell layer (GCL)--mostly retinal ganglion cells--during postnatal development. The changes in the ganglion cell layer were evaluated in Nissl stained wholemount retinal preparations. Additionally, the difference between expansion-related redistribution of cells in the GCL and Muller cells was confirmed in wholemount preparations where Muller cells (identified as vimentin positive) and cells in the GCL (identified by fluorescent supravital dyes) were simultaneously labeled. It is assumed that many of the ganglion cells within the retinal center are not translocated during retinal expansion, possibly because their axons are fixed. In contrast, 5-HT accumulating amacrine cells--which are interneurons without a retinofugal axon--display a passive redistribution together with the surrounding retinal tissue. PMID- 8494801 TI - Neurophysiology of central retinal degeneration in cat. AB - Receptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-threshold curves. Although the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits. PMID- 8494802 TI - A role for 5HT3 receptors in visual processing in the mammalian retina. AB - We investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direct ion channel. PMID- 8494803 TI - Dark-adaptive cone elongation in the blue acara retina is triggered by green sensitive cones. AB - In a dichromatic teleost species, we determined the intensity of light of various wavelengths required to prevent cone elongation by exposing fish at the time of their normal "dusk" phase to monochromatic light (479, 623, and 660 nm) at eight to ten different intensities for 75 min. The positions of single and double cones were measured in tangential sections and expressed as cone indices. At all wavelengths, the spectral responses of both cone types were virtually identical. Furthermore, the sensitivity of the blocking effect was highest at shorter wavelengths. When comparing the relative quantal sensitivities of myoid elongation for the two cone types to the spectral sensitivities of the three types of Aequidens pulcher photoreceptor, we found the closest match between the action spectrum and the absorption spectrum of the green-sensitive single cones. This may indicate that this cone type is capable of reacting directly to decreasing levels of illumination. On the other hand, the identical sensitivity of both cone types argues for an indirect control mechanism of dark-adaptive cone elongation, possibly via a neural pathway involving the inner retinal layers, complementary to the neural control of light adaptation. Green-sensitive single cones are well suited to trigger this response, since (1) their sensitivity is inferior to that of double cones; (2) waters inhabited by the blue acara transmit best at long wavelengths; and (3) at dusk, long-wavelength radiation dominates over other parts of the spectrum. Therefore, green-sensitive cone threshold will be reached first at dusk. PMID- 8494804 TI - Neuromodulation of pigment movement in the RPE of normal and 6-OHDA-lesioned goldfish retinas. AB - The role of dopamine as the endogenous signal-initiating light-dependent changes in the distribution of pigment granules in goldfish retinal pigment epithelium was investigated. In normal retinas, light adaptation resulted in the dispersion of pigment granules. This effect of light was mimicked by the intraocular injection of dopamine or serotonin, which is thought to increase endogenous dopamine release, into dark-adapted eyes. The effect of light, dopamine, or serotonin on dark-adapted retinas was blocked by the dopamine receptor antagonists haloperidol and sulpiride. However, lesioning the endogenous source of retinal dopamine, by prior intraocular injection of 6-hydroxydopamine (6 OHDA), did not block the dispersion of pigment granules in light-adapted retinas. No significant differences in pigment dispersion were noted between unlesioned and lesioned light- or dark-adapted retinas. However, the effect of light on pigment dispersion was no longer blocked by haloperidol or sulpiride in 6-OHDA lesioned animals. Dopamine and serotonin mimicked the effect of light when injected into lesioned dark-adapted eyes, but their effects were also not blocked by haloperidol or sulpiride. These results suggest that dopamine, acting on D2 receptors, is sufficient to induce pigment migration in unlesioned animals. In 6 OHDA-lesioned animals, however, pigment migration is mediated by a receptor mechanism other than D2. PMID- 8494806 TI - Contrast sensitivity to patch stimuli: effects of spatial bandwidth and temporal presentation. AB - Models of the spatial response of human vision are important for applied work, but the available contrast sensitivity function (CSF) data vary widely due to the diverse spatiotemporal stimuli used over the years. To assist selection, this paper: (1) reports measurements of the effects on the CSF of varying the spatial and temporal windows of grating patches; (2) demonstrates that the widely discrepant CSFs from previous studies can be accounted for by using these results; and (3) discusses simple criteria for choosing CSFs for practical applications. CSFs were measured for several combinations of spatial and temporal waveforms, using the same subjects under otherwise identical conditions. The CSF was measured over the range of 0.5-10 c/deg using Gabor-type patches of 1.0-, 0.5 , 0.25-, and 0.125-octave spatial bandwidths using both abrupt and gradual temporal presentations. The results were compared with the CSF obtained with a fixed aperture (4 deg x 4 deg) grating pattern. Increasing the number of cycles resulted in increased sensitivity at intermediate frequencies, changing the CSF to a narrower bandpass shape. For each patch bandwidth, the gradual presentation CSF had a narrower spatial pass band than with the abrupt presentation. The relevance of the large differences in the CSFs obtained with different stimuli to our understanding of visual performance is discussed. PMID- 8494805 TI - Eye alignment and cortical binocularity in strabismic kittens: a comparison between tenotomy and recession. AB - Interocular alignment was assessed by corneal light reflex photography in 15 normal and 26 strabismic kittens. Strabismus was induced at 3-4 weeks of age by severing one extraocular muscle (tenotomy), by cutting and reinserting the muscle at another position on the ocular globe (recession), or by combining recession of the medial rectus muscle with resection of the lateral rectus muscle of the same eye. Nineteen strabismic and five normal kittens were followed longitudinally from 12 days to about 6 months of age. Three out of six longitudinally followed tenotomized cats and six out of the 13 recessed cats conserved their postoperative ocular deviation throughout the testing period ("large-angle strabismics"). Three tenotomized and seven recessed cats showed a transient deviation for 1-2 weeks after surgery, after which the interocular deviation diminished to values found in normal cats ("microstrabismic" cats). Both recessed resected cats showed a transient interocular deviation. In spite of their different developmental histories, all cats showed a clear breakdown of binocularity in area 17. Large-angle strabismics showed a dominance of the non operated eye, while in microstrabismic cats, both eyes were equally effective in driving cortical cells. It thus appears that a transient strabismus is sufficient to produce a reduction of binocularity in area 17. PMID- 8494807 TI - Local gain control and focal accommodation in the Self Similar Stack vision model. AB - The aim of this paper is to report an extension to the computationally efficient Self Similar Stack model (Burton et al. Biol., Cybernet. 53, 397-403, 1986) to include the effects of local gain control in the retina. The method employed to do this has been to fit a family of difference-of-Gaussian functions to the human contrast sensitivity function curves of van Nes and Bouman (J. Opt. Soc. Am. 57, 401-406, 1967). The centre frequencies of the DoGs within each family are octave related, in a simplified manifestation of the DoG channels found by Wilson et al. (Vision Res. 23, 873-882, 1983). The sensitivity of each level, or channel, that formed the original Stack model is modulated individually according to the fitted values, as the local illumination varies within an image. The model was tested against psychometric data obtained by Haig and Burton (Appl. Optics 26, 492-500, 1987) during experiments on visual discrimination. The consistency of the results indicates the validity of the approximations and the robustness of the model, either for machine vision purposes or for predicting human visual performance. A simple algorithm, developed for use with a machine vision application of this model, provides a means by which a TV camera may be focused automatically. The success of this algorithm, using the newly computed channel sensitivities, suggests that human focal accommodation may be regulated by a similar form of mechanism. PMID- 8494808 TI - Optic flow and depth perception. AB - The field of depth recovery from optic flow has recently experienced much growth, both on the theoretical and on the empirical fronts. Unfortunately, the theoretical results are not as widely known to perception workers as they might be. This article gives a simple analysis of the information for depth present in optic flow. It also reviews the psychophysical results for depth recovery from motion. These results are discussed with reference to the theoretical analysis and to relevant computer algorithms for depth recovery. PMID- 8494809 TI - Ocular damage after implantation of oversized minus power anterior chamber intraocular lenses in myopic phakic eyes: case reports. AB - BACKGROUND: Positioning in the iridocorneal angle is one of the factors determining long-term tolerance of anterior chamber intraocular lenses (IOLs). This problem has again become topical with the use of myopic IOLs with angular supports. METHODS: The authors describe three eyes illustrating the possible complications resulting from the insertion of oversized minus power anterior chamber implants in myopic phakic eyes. RESULTS: The complications developed early or late after surgery. They consisted mainly of inflammatory reactions, stable or progressive pupillary deformation, and adherence of the iris to the implant. CONCLUSIONS: In myopic phakic eyes, the insertion of incorrectly sized IOLs with angular supports may cause complications which have already been reported for anterior chamber implants in aphakic eyes. Haptic flexibility does not always make up for incorrect sizing due to imprecise preoperative evaluation of iridocorneal angle diameter. PMID- 8494810 TI - Effect of corneal hydration on Goldmann applanation tonometry and corneal topography. AB - BACKGROUND: Measured ocular tension is reported to be positively related to corneal thickness. It has been speculated that an edematous cornea will cause low measurements. We studied the effects of corneal hydration on applanation tonometry and biomechanical behavior of the cornea. METHODS: This study examines the effects of corneal hydration on applanation tonometry on four human cadaver eyes with the Goldmann Schmidt tonometer and on one cadaver eye with the Tono-Pen 2. Hydration was controlled osmotically and assessed by ultrasonic pachometry. True intraocular pressure (IOP) was controlled and was measured by a piezoelectric pressure transducer. The effect of hydration and IOP on anterior curvature was also assessed with computer topography. RESULTS: The results of this study show an inverse relationship between corneal hydration and ocular tension measured with applanation tonometry. The Goldmann readings decreased by 9.2 +/- 0.7 mm Hg as the cornea is taken from minimum to maximum hydration. Anterior curvature was affected very little by hydration or increased IOP. CONCLUSIONS: This study has shown, in vitro, that the tonometer readings are inversely related to its thickness when the cornea is edematous. The clinical implication is that when performing applanation tonometry, the hydration status of the cornea must be carefully examined to avoid possible diagnostic error. PMID- 8494811 TI - Seventh annual Lans distinguished refractive surgery lecture.. PMID- 8494812 TI - Lans Lecture: refractive surgery and your practice. PMID- 8494813 TI - Prognosis for penetrating keratoplasty in iridocorneal endothelial syndrome. AB - BACKGROUND: Iridocorneal endothelial syndrome is characterized by the proliferation and spreading of an abnormal corneal endothelial membrane across the iridocorneal angle and iris surface, resulting in iridocorneal adhesions, glaucoma, pupillary distortion, varying degrees of iris atrophy, and occasionally corneal decomposition with edema. These changes may possibly affect the long-term prognosis of penetrating keratoplasty in an adverse fashion. METHODS: We reviewed the clinical course of 12 consecutive eyes (12 patients) which underwent penetrating keratoplasty for corneal edema associated with the iridocorneal endothelial syndrome (mean postoperative follow up = 30 months). RESULTS: The grafts remained clear in 10 patients (83%) and the visual acuity was 20/40 or better in nine patients (75%). The endothelial cell losses averaged 13% at 6 months and 17% at 1 year after surgery. Simultaneous extracapsular cataract extraction and posterior chamber lens implantation at the time of keratoplasty posed no measurable compromise to the overall postoperative prognosis. Causes of poor visual acuity after surgery included glaucoma and graft failure (immune and nonimmune). CONCLUSIONS: The prognosis of penetrating keratoplasty in the iridocorneal endothelial syndrome appears to be very favorable in the majority of eyes. PMID- 8494814 TI - Radial keratotomy in intact epikeratoplasty graft. AB - BACKGROUND: Epikeratoplasty can be used to flatten the cornea in keratoconus but is not a satisfactory tool to correct refractive errors in this setting. Radial and astigmatic keratotomy are unpredictable in keratoconus but can be used in an eye which has previously undergone epikeratoplasty for keratoconus. METHODS: We report a case of a pseudophakic eye with Keratoconus which received epikeratoplasty and subsequently underwent radial and astigmatic keratotomy in the graft. RESULTS: Before the refractive keratotomy, the patient had a refraction of -8.00 + 3.25 x 25. At 5 months after radial and astigmatic keratotomy, the patient had an uncorrected visual acuity of 20/60+ with a refraction of -0.50 + 2.00 x 28. CONCLUSIONS: This case demonstrates how different types of refractive corneal surgery can be combined to improve visual acuity in an individual patient. Whether the specific combination of epikeratoplasty and refractive keratotomy can be advocated in the treatment of keratoconus requires more experience with a greater number of patients. PMID- 8494815 TI - Human lamellar tendon graft in corneal surgery. AB - BACKGROUND: Due to the lack of donor corneas or unsuitable conditions for keratoplasty because of preexisting conditions such as vascularization, infections, and multiple rejections, scientists have searched for new synthetic and biological materials that can temporarily or permanently substitute for corneal tissue. The purpose of this article is to show our personal experiences with the use of commercially available donor tendon tissue which has been chemically treated and was developed by Muldashev. METHODS: Ten eyes unsuitable for a corneal allograft underwent lamellar keratoplasty using tendon allografts. Due to differing pathologies various surgical procedures were used. The follow-up period ranged from 6 to 18 months. RESULTS: Transparent or semitransparent corneas resulted in seven of the ten eyes. In the three remaining eyes, conditions were improved for future penetrating keratoplasty because there was a significant decrease in corneal vascularization. The donor tendon was not rejected in any case. CONCLUSIONS: As an alternative therapeutic method, treated human tendon proved effective as donor material for lamellar keratoplasty. PMID- 8494816 TI - Lamellar keratoplasty with lyophilized tissue for treatment of corneal scarring. AB - BACKGROUND: A pilot study was carried out in Pakistan to assess the feasibility of the use of lathed freeze-dried corneal tissue in the treatment of corneal scarring. METHOD: Six eyes underwent lamellar keratoplasty and were followed up for 18 months. RESULTS: Visual improvement was obtained in every eye. In one eye, the procedure was complicated by delayed epithelialization of the graft, but in the remaining five patients, the grafts epithelialized rapidly. CONCLUSIONS: The use of freeze-dried donor tissue simplifies storage and distribution of corneas and may offer the best hope of treatment in developing countries for patients with corneal scarring. PMID- 8494817 TI - Is corneal contour influenced by tension in the superficial epithelial cells? PMID- 8494818 TI - Excimer laser photorefractive keratectomy for myopia: results in 1165 eyes. Italian Study Group. AB - BACKGROUND: We report the results of a prospective study conducted in Italy to evaluate the efficacy, safety, predictability, and complications of excimer laser photorefractive keratectomy for the correction of myopia. METHODS. Photorefractive keratectomy was performed on 1236 myopic sighted eyes in 16 centers, using the Summit Excimed 193 nm excimer laser. The attempted correction ranged from -0.80 to -25.00 diopters (mean, -7.83 +/- 3.88 D). The population was divided into three groups of attempted correction: between -0.80 and -6.00 D, between -6.10 and -9.90 D, and between -10.00 and -25.00 D. We report the data of 1165 eyes at 1 month, 970 eyes at 3 months, 752 at 6 months, and 330 at 12 months. At each visit, we evaluated (1) the refractive changes over time; (2) the difference between attempted and achieved correction; (3) uncorrected and best spectacle corrected visual acuity; and (4) haze. RESULTS: Twelve months after surgery, the spherical equivalent refractive error in 146 eyes with attempted correction of -0.80 to -6.00 D was -0.52 +/- 1.04 D; 104 eyes (71.2%) were within +/- 1.00 D of attempted correction. In 145 eyes with attempted correction of 6.10 to -9.90 D, the spherical equivalent refractive error was -1.66 +/- 1.88 D; 50 eyes (34.5%) were within +/- 1.00 D of attempted correction. The spherical equivalent refractive error in 39 eyes with attempted correction of -10.00 to 25.00 D was -1.86 +/- 3.47 D; 11 eyes (28.2%) were within +/- 1.00 D of attempted correction. Eight eyes (2.4%) lost two or more Snellen lines of best spectacle corrected visual acuity. None of the treatments caused severe postoperative complications, or scarring. CONCLUSIONS: Photorefractive keratectomy proved safe and effective, but highly predictable only in the correction of myopia up to 6.00 D. PMID- 8494819 TI - Antigen presenting cell-derived co-stimulatory signals can selectively regulate IL-2 and IL-4 production from a Th0 cell hybridoma. AB - Th0 cells are a subpopulation of Th cells that produce both IL-2 and IL-4. In order to study the selective regulation of lymphokines in Th0 cells, a Th0 cell hybridoma, GA15, was generated by fusing a Th2 clone with the thymoma BW5147. The pattern of lymphokines secreted by GA15 was found to depend on the antigen presenting cells (APC) used for stimulation. When GA15 was stimulated with antigen and splenocytes, both IL-2 and IL-4 were produced. However, when the B cell hybridoma LB was used as APC, only IL-2 was detected. Although LB cells could not stimulate IL-4 production, they were more potent than were spleen cells at inducing IL-2 production, demonstrating that the difference between the two APC populations was qualitative rather than quantitative. Similar results were seen upon stimulation with concanavalin A or anti-CD3 epsilon mAb. Regulation of interferon-gamma production paralleled regulation of IL-4 production. The failure of LB cells to stimulate IL-4 production was not due to inhibition or consumption of IL-4 and the activity could not be restored by adding IL-1, spleen cell supernatants or spleen cells lacking the appropriate MHC molecule. Finally, the parent Th2 clone used in the fusion showed a similar inability to produce IL-4 in response to LB cells. These data indicate that APC-derived co-stimulatory signals can selectively affect IL-2 and IL-4 production in a Th0 cell hybridoma. Therefore, the choice of APC may lead to selective stimulation of particular lymphokines by acting on Th0 cells. PMID- 8494820 TI - Emigration of selected subsets of gamma delta + T cells from the adult murine thymus. AB - Cells bearing the gamma delta form of the TCR make up only 1-3% of T cells in the adult murine thymus and peripheral lymphoid organs. Evidence from studies of nude mice suggests that the development of at least some gamma delta T cells is thymus dependent; however, until now it has not been directly demonstrated that gamma delta cells are exported from the thymus. In this paper we have used the technique of labelling thymocytes in vivo with FITC, followed by flow cytometric analysis to trace cells emigrating from the thymus to the spleen. Using this approach we have been able to demonstrate for the first time that gamma delta T cells are exported from the adult murine thymus to the spleen. We also demonstrate that the cells emigrating to the spleen are a selected subset of gamma delta thymocytes being heat stable antigen positive, Thy-1+, and expressing low levels of CD44 (Pgp-1). In addition, investigation of TCR V gamma gene usage among adult gamma delta + thymocytes, recent emigrants, and spleen cells, indicated a selective emigration of gamma delta cells expressing certain V gamma genes. PMID- 8494821 TI - Reconstitution of the functional granulocyte macrophage colony stimulating factor promoter: evidence for distinct activation mechanisms that mediate the response to phorbol ester/calcium and human T cell leukemia virus type I Tax signals. AB - Functional elements in the promoter region of the mouse granulocyte-macrophage colony stimulating factor (GM-CSF) gene were assessed by constructing chimeric promoters linked to the bacterial chloramphenicol acetyltransferase (CAT) gene and by employing a transient transfection assay of human T cell leukemia Jurkat cells. We previously reported that CLE2/GC-box (at positions -95 to -73, which is homologous to the NF-kappa B binding site) and CLE0 (at positions to -40) of the mouse GM-CSF promoter are essential for transcriptional activation in response to phorbol-12-myristate-13-acetate (PMA)/calcium ionophore (A23187). Here we show that CLE2/GC-box and the NF-kappa B binding motif are functionally interchangeable and that CLE2/GC-box and CLE0 as a unit activate the basic GM-CSF promoter in response to PMA/calcium signals. This unit is also capable of activating heterologous promoters in response to PMA/calcium signals. In addition, we show that Tax, the trans-activator encoded by human T cell leukemia virus type I (HTLV-I), activates the GM-CSF promoter via CLE2/GC-box without the involvement of CLE0. These results indicate that PMA/A23187-dependent and Tax dependent activation of the GM-CSF gene proceeds through distinct mechanisms. PMID- 8494822 TI - Residues in pockets B and F of HLA-B27 are critical in the presentation of an influenza A virus nucleoprotein peptide and influence the stability of peptide - MHC complexes. AB - Six pockets, designated A through F, which extend from the peptide binding site of class I HLA molecules, have been postulated to play an important role in determining peptide binding specificity. HLA-B27 mutant molecules with single amino acid substitutions at residues 9his-->phe, 24thr-->ser, 45glu-->thr, and 67cys-->ala in pocket B; 114his-->asn in pocket D; and 116asp-->phe in pocket F have been generated and characterized for their capacity to present an influenza A nucleoprotein peptide (NP 383-391) for cytotoxic T lymphocyte recognition. We report here that substitutions in residues 45, 67, and 116 affect presentation of NP 383-391 when peptide is processed and loaded during viral infection. Using 125I-labeled NP peptide, we demonstrate that substitutions in residues 67 and 116 alter the stability of NP-HLA-B27 complexes. A substitution at position 9 of the NP peptide complements the mutation introduced at residue 116, suggesting that the NP peptide binds with its carboxy terminal amino acid in pocket F. These findings indicate that polymorphic residues within pockets B and F of HLA-B27 play a crucial role in peptide binding and stability of peptide-MHC class I complexes. Furthermore, our results suggest that substitutions at allele-specific residues within pockets B and F alter the stability of NP-HLA-B27 complexes resulting in the diminution or abrogation of NP presentation during viral infection. PMID- 8494823 TI - Spontaneous and antibody directed cytotoxicity of double-negative T cells from autoimmune mice. AB - MRL/Mp-lpr/lpr (MRL/lpr) mice develop a syndrome similar to systemic lupus erythematosus in humans. This strain of mice is characterized by the progressive accumulation of CD4-CD8- (double-negative; DN) T cells which express increased levels of cell adhesion molecules such as CD44 and heat stable antigen (HSA). The DN T cells exhibited a higher level of spontaneous cytolytic activity and contained a higher level of serine esterase as compared with T cells of MRL/Mp +/+ (MRL/+) mice. We also found that mAbs against CD44, Mel-14, CD45R, and HSA could augment the cytolytic activity of DN T cells of MRL/lpr mice. Antibody mediated augmentation of cytolytic activity of DN T cells was due to conjugate formation in which the Fc portion of mAb bound to the Fc gamma receptor on target cells and the Fab portion of mAb bound to corresponding cell surface antigens on DN T cells. The antibody-mediated augmentation of cytolytic activity was not detected in T cells of MRL/+ mice and lymphokine activated killer (LAK) cells of C57BL/6 mice. In contrast, anti-CD3 mAbs could augment the cytolytic activity of DN T cells, T cells as well as LAK cells. mAbs against LFA-1 and VLA-4 failed to augment the cytolytic activity of three different effector cells. It should be noted that anti-CD3 mAb-mediated cytolytic activity of DN T cells was substantially reduced by anti-LFA-1 mAb. However, CD44, Mel-14, CD45R as well as HSA-mediated cytolytic activity of DN T cells was not inhibited by anti-LFA-1 mAb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494824 TI - Pathogen-induced Th1 phenotype development in CD4+ alpha beta-TCR transgenic T cells is macrophage dependent. AB - We used an ovalbumin (OVA)-specific alpha beta-TCR transgenic mouse system to examine the cellular basis of CD4+ T helper (Th) phenotype development in vitro. Heat-killed Listeria monocytogenes (HKLM) strongly promotes the in vitro development of a Th1 phenotype in OVA-specific transgenic T cells. Listeria monocytogenes effects to promote the Th1 phenotype are antigen presenting cell (APC) dependent and occur when splenic APCs, but not the B cell hybridoma TA3, are present during T cell activation. However, addition of FACS-sorted macrophages to TA3 activated cultures restores the ability of Listeria to induce Th1 development. This effect on T cell development does not require MHC restricted antigen presentation by macrophages, but may act through soluble factors. Although the presence of interferon gamma is necessary for Listeria induction of Th1 development, IFN-gamma alone is insufficient to induce Th1 development. Furthermore, Listeria induction of the Th1 phenotype does not require several known products of activated macrophages, including interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha), IL-6, or nitric oxide. Although transforming growth factor-beta (TGF-beta) may mediate some Listeria effects, it does not fully reconstitute Listeria effects to promote Th1 development. In summary, host interactions with bacterial pathogens can affect the development of specific Th subsets, allowing innate immune cells to direct development of specific immune phenotype. For Listeria monocytogenes, the induction of the Th1 phenotype may involve a novel cytokine distinct from several known factors produced by activated macrophages. PMID- 8494825 TI - Scid mouse Pre-B cells with intracellular mu chains: analysis of recombinase activity and IgH gene rearrangements. AB - Four Pre-B cell clones with intracellular mu chains were recovered from individual leaky scid mice by transformation of bone marrow or peritoneal cells with Abelson murine leukemia virus. Three clones were derived from independent bone marrow cell cultures. These express the defective scid recombinase activity and contain truncated mu chains resulting from abnormal and/or incomplete (D to J only) gene rearrangements. A fourth clone was obtained from a peritoneal cell culture and may represent a revertant. It expresses a recombinase activity indistinguishable from that of wild-type cells; one of its rearranged IgH alleles (VDJ+) encodes a normal size mu chain, the other is non-productively rearranged (VDJ-). PMID- 8494826 TI - Lymphokine synthesis in vivo in an acute murine graft-versus-host reaction: mRNA and protein measurements in vivo and in vitro reveal marked differences between actual and potential lymphokine production levels. AB - The in vivo activation of lymphokine-producing cells was analyzed in the first 7 days of an acute graft-versus-host reaction (GVHR) induced by injection of C57BL/6 spleen cells into irradiated DBA/2 mice. Although the GVHR was accompanied by a 1000-fold increase in serum IL-6 titers, circulating levels of other lymphokines were low (IL-3, IFN-gamma, and GM-CSF) or undetectable (IL-2 and IL-4). Spleen and lymph node cells from these mice nevertheless produced elevated levels of IL-3, IFN-gamma, GM-CSF, and IL-6 when cultured for 24 h without stimulation; culture with anti-CD3 antibody further increased IL-2, IL-3, IL-4, IFN-gamma, and GM-CSF production by at least 20-fold. Both constitutive and anti-CD3-induced synthesis of all the lymphokines was mediated by CD3+ cells. Messenger RNA analyses revealed the presence of IL-6, IFN-gamma, and GM-CSF transcripts in freshly harvested GVHR spleen cells and increased expression of IL 2, IL-3, IL-4, IFN-gamma, and GM-CSF mRNAs following anti-CD3 stimulation in vitro. In vivo, however, IL-3 mRNA was barely detectable even following cDNA amplification by polymerase chain reaction. In vivo restimulation of day 5 GVHR mice by injection of concanavalin A enhanced expression of IL-3, IL-6, IFN-gamma, and GM-CSF mRNAs and markedly increased serum titers of the corresponding lymphokines, which peaked 6-12 h after injection at levels at least 10- to 100 fold higher than in concanavalin A-treated normal mice.2+ for high-level synthesis of all these lymphokines. PMID- 8494827 TI - Cyclosporin A inhibits the decrease of CD4/CD8 expression induced by protein kinase C activation. AB - Cyclosporin A (CsA) is a powerful immunosuppressive drug widely used in transplantation medicine. A major effect of CsA is inhibition of the differentiation of immature double-positive (DP) CD4+ CD8+ thymocytes into mature single-positive (SP) CD4+ CD8- or CD4- CD8+ thymocytes. The mechanisms underlying the changes in CD4/CD8 expression during normal differentiation of thymocytes and the way CsA interferes with this differentiation process are still unknown. Here we show that protein kinase C (PKC) activation by phorbol 12-myristate 13-acetate (PMA) causes a decrease of both CD4 and CD8 expression at the cell surface level and at the mRNA level in a CD4+ CD8+ T cell line and in freshly isolated thymocytes. A PKC inhibitor, staurosporin, interferes with the differentiation from DP to SP in fetal thymus organ culture system. These data suggest that the alternation of CD4/CD8 expression from DP to SP is dependent on PKC activation. CsA blocks this decrease of CD4/CD8 expression by PMA in vitro. Moreover, this PMA effect is also blocked by treatment with cycloheximide. These results suggest that the reduction of CD4/CD8 expression requires de novo synthesis of a protein(s) induced in response to a signal conveyed by activated PKC. CsA may block the transition from DP to SP by inhibition of CD4/CD8 down-regulation induced by PKC activation. PMID- 8494828 TI - Obstetric intervention and the economic imperative. PMID- 8494829 TI - Fibronectin: a predictor of preterm delivery? PMID- 8494830 TI - Fractured clavicle of the newborn. PMID- 8494831 TI - Labour induction policy in hospitals of different levels of specialisation. AB - OBJECTIVE: To examine indications for the induction of labour and variations in the current policy of induction at different levels of obstetric specialisation and to compare the outcome of induced and spontaneous labour. DESIGN: A prospective 1 year birth cohort. SETTING: Maternity hospitals in the two northernmost administrative provinces of Finland, including one university hospital and three central hospitals, three local hospitals and five health centres. SUBJECTS: Eight thousand six hundred and six singleton pregnancies, including 1679 with induced labour. MAIN OUTCOME MEASURE: Data collection on age, parity, social factors and education at antenatal clinic. Data on labour collected from the hospital records after delivery. RESULTS: Labour was induced significantly more often at units of the lowest level of specialisation, the health centres (29.4%) than at the local hospitals (23.6%, P < 0.003) or in the most specialised central hospitals (17.7%, P < 0.0001). Cases of induced labour accumulated on working days. Indicative reasons, such as maternal or fetal conditions, comprised 45.0% of the indications for induction, the most common causes being elective reasons, e.g. timing of labour (51.3%). The risk of elective induction was 2.6 times greater at the primary care level than at the central hospitals (95% confidence limit, CL 2.0-3.2). The corresponding risk ratio for local hospitals was 1.8 (CL 1.5-2.1). The risk of caesarean section was 1.5 times greater in the elective induction group than in the spontaneous group (CL 1.1-1.9) and 2.9 times greater in the indicative induction group. The most common indication for caesarean section was dysfunctional, arrested labour, causes such as fetal asphyxia or antenatal haemorrhage were not seen in excess. CONCLUSION: The practice of induction of labour are not consistent in different hospitals. The opinions of individual practitioners and staff routines influence the induction policy nearly as much as do medical reasons. Despite the safety of induction, a liberal induction policy leads to an increase in operative deliveries creating potential risks for the mother and child and greater expense. PMID- 8494832 TI - Simulated home delivery in hospital: a randomised controlled trial. AB - OBJECTIVES: To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife-led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant-led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out. DESIGN: Randomised controlled trial. SETTING: Leicester Royal Infirmary Maternity Hospital. SUBJECTS: Of 3510 women who were randomised, 2304 were assigned to the midwife-led scheme and 1206 were assigned to the consultant-led scheme. MAIN OUTCOME MEASURES: Complications in the antenatal, intrapartum and postpartum periods were compared as was maternal morbidity and fetal mortality and morbidity. Satisfaction of the women with care over different periods of the pregnancy and birth were assessed. RESULTS: There were few significant differences in antepartum, intrapartum and postpartum events between the two groups. There was no difference in the percentage of mothers and babies discharged home alive and well. Generally higher levels of satisfaction with care antenatally and during labour and delivery were shown in those women allocated to midwife care. PMID- 8494833 TI - Postpartum haemorrhage in Zimbabwe: a risk factor analysis. AB - OBJECTIVES: To identify risk factors associated with postpartum haemorrhage (PPH) in order to improve the effectiveness of antenatal screening. DESIGN: A population-based case control study. SETTING: Harare, Zimbabwe. SUBJECTS: Two groups of women, one group consisting of those with postpartum haemorrhage after a normal vaginal delivery and the other of women with normal unassisted vaginal delivery without PPH. METHOD: Data abstracted from the medical records; relative risks were estimated by multivariate logistic regression. RESULTS: Low parity, advanced maternal age, and antenatal hospitalisation were among the strongest risk factors, with more modest associations for history of poor maternal or perinatal outcomes and borderline anaemia at the time of booking. No association with grand multiparity was found. CONCLUSIONS: These findings confirm the importance of previously recognised factors such as low parity, poor obstetric history, anaemia, and prolonged labour, but call into question the significance of grand multiparity. Previously undocumented factors such as maternal age greater than 35 years and occiput posterior head position emerged as predictors worthy of further investigation. PMID- 8494834 TI - Fractured clavicle of the newborn in a population with a high prevalence of grand multiparity: analysis of 78 consecutive cases. AB - OBJECTIVE: To perform a clinical analysis of newborn babies with a fractured clavicle and investigate the possible role of relative calcium deficiency in the aetiology. DESIGN: Prospective descriptive study (clinical aspects); case controlled study (calcium, phosphate, alkaline phosphatase). SETTING: The Nazareth Hospital, Israel. SUBJECTS: All babies with a fractured clavicle detected in the newborn period and their mothers delivered between 23 August 1987 and 22 June 1989. The majority of the population were Arab. INTERVENTIONS: Serum calcium, phosphate and alkaline phosphatase were measured on the third postpartum day in 42 affected babies (with uncomplicated deliveries), their mothers, and a matched group of babies and mothers as controls. MAIN OUTCOME MEASURES: Clinical associations of fractured clavicle of the newborn; statistical comparison of affected group with controls (calcium study). RESULTS: The incidence of fractured clavicle was 18.7 per 1000 singleton vaginal births; 38 in the posterior clavicle at delivery, 27 in the anterior, position unascertained in nine. Four (5.2%) occurred in instrumental deliveries, three (3.9%) in assisted breech delivery; shoulder dystocia was noted in 13. The male to female ratio of 51:26 was significantly different but not due to birth weight. Affected babies were significantly heavier than the unaffected population. The incidence was higher in parous mothers older than 25 years of age but there was no evidence of increased incidence with increasing parity. No significant results were obtained in the calcium study between affected babies and their mothers, when compared with controls. CONCLUSIONS: Fractured clavicle of the newborn is a benign form of birth trauma from which heavier babies are at greater risk. It occurs in 1 to 2% of deliveries, most of these being uncomplicated vaginal births, and is often undetected. There is no evidence for relative calcium deficiency. PMID- 8494835 TI - The individualised birthweight ratio: a more logical outcome measure of pregnancy than birthweight alone. AB - OBJECTIVE: To provide a new outcome measure for pregnancy specifically related to the individual. DESIGN: Computer analysis of physiological factors affecting birthweight. SETTING: Two provincial teaching hospitals (University and City Hospitals, Nottingham) and an associated district general hospital (Derby City Hospital) serving a defined catchment area in the East Midlands. SUBJECTS: All women delivering in the above hospitals since the start of computerised obstetric records: 31,561 women with gestational age verified by early pregnancy ultrasound scan data. MAIN OUTCOME MEASURES: Calculation of the predicted birthweight taking into account maternal and fetal physiological factors. Derivation of the individualised birthweight ratio (actual birthweight divided by predicted birthweight expressed as a percentage) for each individual baby. RESULTS: The individualised birthweight ratio redefines as normally grown 41% of babies below the 10th centile of crude birthweight for gestation. Other babies previously regarded as normal are redefined as growth retarded. At the upper end of the distribution 46% of those above the 90th centile of birthweight for gestation are redefined as normally grown. CONCLUSIONS: The predicted birthweight can be calculated for an individual pregnancy at a given gestation. The standardised comparison between this predicted birthweight and the actual birthweight is a more logical reflection of the normality of intrauterine growth and therefore more logical as an outcome measure for pregnancy than crude birthweight for gestation. PMID- 8494836 TI - Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women. AB - OBJECTIVE: To compare the serum levels of gonadotrophins and androgens, as well as ovarian morphology, in 50 women with a history of recurrent miscarriage and in 20 healthy controls. DESIGN: Prospective study on women with a history of at least three consecutive miscarriages in Department I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Finland. RESULTS: The recurrent miscarriage group as a whole exhibited gonadotrophin and androgen levels comparable to those seen in the controls. Ultrasound examination revealed polycystic ovaries (PCO) in 22 patients (44%) and in four control women (20%, P = 0.06) but no differences in the levels of gonadotrophins and androgens emerged between the patients with or without PCO. During follow up, 33 (66%) women with a history of recurrent miscarriage who became pregnant; 16 miscarried again (48.5%), whereas 17 (51.5%) succeeded. The presence of PCO did not predict miscarriage, but the patients who miscarried had higher levels of total testosterone, free testosterone and dehydroepiandrosterone sulphate than RSA women with continuing pregnancies. CONCLUSIONS: PCO and hyperandrogenism may be associated with repeated miscarriage. PMID- 8494837 TI - An alternative to hysterectomy? GnRH analogue combined with hormone replacement therapy. AB - OBJECTIVE: To assess whether GnRH analogues are effective in relieving pelvic pain and congestion and whether menopausal symptoms caused by GnRH analogues can be minimised by supplementation with low dose continuous combined hormone replacement therapy (HRT). DESIGN: Open prospective study. SETTING: Tertiary referral clinic at a teaching hospital. PATIENTS: Twenty-one women with chronic pelvic pain. INTERVENTION: Four months' therapy with goserelin 3.6 mg/month combined with continuous oestradiol valerate 1 mg daily and medroxyprogesterone acetate 5 mg daily. MAIN OUTCOME MEASURES: Visual analogue scale for pain, menopausal symptoms, bleeding patterns, uterine area, endometrial status, oestradiol concentrations and venogram scores. RESULTS: Amenorrhoea was maintained in all but two women. Endometrial atrophy was maintained despite HRT supplementation. Two women had moderate menopausal symptoms but none had severe symptoms. Significant reduction of uterine cross sectional area was maintained throughout the study. There was no significant relief of pain. CONCLUSIONS: HRT supplementation of GnRH analogues abolishes menopausal symptoms and thus may improve patient acceptability. Potentially beneficial effects such as endometrial atrophy, reduction of uterine volume and amenorrhoea were not negated by HRT. This combination is not effective in the treatment of chronic pelvic pain and congestion. PMID- 8494838 TI - Assisted conception using buserelin and human menopausal gonadotrophins in women with polycystic ovary syndrome. AB - OBJECTIVE: To compare the outcome of in vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) cycles in women with or without ultrasound features of polycystic ovary syndrome (PCOS). DESIGN: A consecutive series from January to December 1989. SUBJECTS: Twenty-five women with PCOS scheduled for assisted conception. The controls were 139 women with normal ovaries. SETTING: A single centre specialist fertility unit, Manchester, UK. INTERVENTIONS: Pituitary desensitisation was with buserelin. In the PCOS group ovarian stimulation was with 1 ampoule (75 iu FSH) of hMG/day in 12 women (Group I) and two ampoules/day in 13 (Group II). The controls (Group III) were given two ampoules of hMG daily. Human chorionic gonadotrophin (hCG; 10,000 iu) was given when three follicles measured > or = 20 mm diameter. MAIN OUTCOME MEASURES: Serum oestradiol (E2) concentrations, number of follicles, clinical pregnancies, features of the ovarian hyperstimulation syndrome (OHS). RESULTS: Women with PCOS (Groups I or II) had more follicles > or = 14 mm diameter on the day of the hCG injection (P < 0.005), higher serum E2 concentrations on the day after the hCG (P < 0.05) and more oocytes retrieved (P < 0.05) than the controls. The OHS was more prevalent in those with PCOS (32% versus 6.5%; P < 0.05). The clinical pregnancy rate per embryo transfer (27% versus 22%) or gamete transfer (25% versus 39%) and the rate of spontaneous miscarriage (33% versus 12%) were not statistically different. CONCLUSIONS: The pregnancy rate and outcome of pregnancy following IVF or GIFT in women with or without PCOS are similar. Women with PCOS are at a higher risk of developing OHS. PMID- 8494839 TI - Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre eclampsia and hydatidiform mole. AB - OBJECTIVE: To examine the behaviour of the major inhibitors of fibrinolysis (PAI 1 and PAI-2) in normal pregnancy and pregnancy complicated by either pre eclampsia or hydatidiform mole. DESIGN: Prospective study. SETTING: Antenatal Clinic and Maternity Hospital. SUBJECTS: Eleven women with established pre eclampsia and eleven women, matched by age, parity, and duration of pregnancy who were undergoing uncomplicated pregnancy. Two women having surgery for hydatidiform mole. MAIN OUTCOME MEASURE: Plasma levels of PAI-1 and PAI-2 antigens determined by sensitive specific ELISA. Functional identification of PAI 2 by nondenaturing gel electrophoresis with overlay zymography. RESULTS: In pre eclampsia PAI-2 antigen was significantly lower than in normal pregnancy (105.3 +/- 34.9 versus 187.1 +/- 67.9 ng/ml; P < 0.001). In contrast PAI-1 antigen was significantly higher in pre-eclampsia than in normal pregnancy (170.7 +/- 71.2 versus 113.8 +/- 35.6 ng/ml; P < 0.05). In consequence the ratio of PAI-1/PAI-2 increased markedly in pre-eclampsia (2.5 versus 0.6). No PAI-2 was detected in plasma of women with hydatidiform moles. CONCLUSIONS: PAI-2 levels fell significantly in pre-eclampsia probably as a result of decreased placental mass or function. The raised PAI-1 level in pre-eclampsia may reflect a response to hypertension or renal damage that is not specific to pregnancy or may reflect altered placental function. The use of the ratio of PAI-1/PAI-2 assists in separating normal from abnormal pregnancies. PMID- 8494840 TI - Changes in platelet intracellular free calcium in normal pregnancy. AB - OBJECTIVE: To determine if platelet intracellular free calcium concentration (p.(Ca2+)i) changes with gestation in normotensive, uncomplicated pregnancy. DESIGN: A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulliparous nonpregnant volunteers. SETTING: The antenatal clinic at University Hospital, Queen's Medical Centre, Nottingham. SUBJECTS: Two groups of women were studied. Thirty-one nulliparous, nonpregnant women not using oral contraception were investigated in the early follicular phase of their menstrual cycles. Also, 24 primigravid women with normotensive, uncomplicated pregnancies were investigated on eight separate occasions during their pregnancies. RESULTS: A significant increase in mean p.(Ca2+)i was demonstrated by 28 weeks gestation in the pregnant women as compared to the nonpregnant control group and the same individuals when investigated at 12 weeks postpartum (P < 0.05; ANOVA). This change was maximal at 36 weeks gestation (P < 0.001; ANOVA); concentrations had returned to those not significantly different from nonpregnant women by six weeks postpartum. CONCLUSIONS: Basal platelet (Ca2+)i increases significantly by the third trimester of normal, primigravid pregnancy as compared to pregnancy values and postnatal values. These data mirror the previously described observations of platelet behaviour noting increased activity at this gestation of pregnancy. It may be that the increased basal p.(Ca2+)i indicates that smaller transient signals have to be generated to induce platelet activity, such as shape change, aggregation and exocytosis. PMID- 8494841 TI - Trends in multiple deliveries and infertility treatments in France. AB - OBJECTIVE: To point out the association between infertility treatments and the increasing number of multiple deliveries. DESIGN: Comparison over time of the incidence of multiple deliveries, the proportion of deliveries resulting from assisted conception (AC), and ovulation inductor sales. DATA: Use of existing statistics: vital statistics, surveys of AC centres and ovulation inductor sales. RESULTS: Between 1972 and 1989 the incidence of twin deliveries rose from 8.8/1000 to 11.2/1000, and the incidence of triplet deliveries from 0.9/10,000 to 4.4/10,000. This upward trend was particularly remarkable among women aged 30 to 39. Since 1978, the triplet delivery rates and the sales of Human Menopausal Gonadotrophin have been rising similarly. Between 1985 and 1989, 26 per cent of the triplet deliveries followed assisted conception and nearly 50 per cent were estimated to be due to ovulation inductor agents. CONCLUSIONS: The results suggest a strong influence of infertility treatments and especially ovulation inductor agents in the dramatic increase of triplet deliveries. PMID- 8494842 TI - Tamoxifen induced adenomyosis and adenomyomatous endometrial polyp. PMID- 8494843 TI - Epidemic of conjoined twins in Cardiff. PMID- 8494844 TI - Osseous metaplasia of the endometrium treated by hysteroscopic resection. PMID- 8494845 TI - Modulation of decidual stromal cell activity by interleukin-1 beta and interleukin-6. PMID- 8494846 TI - Transferrin receptor expression in fetal blood mononuclear cells. PMID- 8494847 TI - 25 mg oestradiol implants--the dosage of first choice for subcutaneous oestrogen replacement therapy. PMID- 8494848 TI - Survival time after AIDS in pregnancy. PMID- 8494849 TI - The variability of cardiopulmonary adaptation to pregnancy at rest and during exercise. PMID- 8494850 TI - Compliance with hormone replacement therapy (HRT) after screening for post menopausal osteoporosis. PMID- 8494851 TI - Expanding the role of vitrectomy in retinal reattachment surgery. PMID- 8494852 TI - Ocular complications of diabetes after cataract extraction. PMID- 8494853 TI - Pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment uncomplicated by advanced proliferative vitreoretinopathy. AB - A consecutive series of 114 eyes (112 patients) undergoing pars plana vitrectomy for rhegmatogenous retinal detachment not complicated by severe proliferative vitreoretinopathy is presented (follow up 1 to 4 years; mean 19 months). The indications for vitrectomy fell into two main groups: (1) where the retinal view was poor and vitrectomy was required to clear media opacities to allow identification of retinal breaks (n = 62); and (2) where technically difficult breaks existed and vitrectomy with internal tamponade was used to relieve vitreoretinal traction and facilitate retinal break closure (n = 44). In some of these cases the need for scleral buckling was eliminated. A smaller third group (n = 8) existed where the position of the break(s) was uncertain in the presence of an adequate view. The success rate with one procedure was 74% and with further surgery retinal reattachment was achieved in 92%. At 6 months after further surgery, beyond which interval no new failures were encountered, best corrected visual acuity was improved in 92 eyes (81%), unchanged in 14(12%), and worse in eight (7%). We conclude that pars plana vitrectomy is an effective method for treatment of selected cases of rhegmatogenous retinal detachment not complicated by proliferative vitreoretinopathy. PMID- 8494854 TI - Removal of silicone oil following diabetic vitrectomy. AB - The outcome of the removal of silicone oil from previously vitrectomised diabetic eyes was studied in a series of 25 eyes in 24 patients. Originally the patients presented with complex retinal detachments associated with proliferative diabetic retinopathy and all had reattached retinas after the initial operation. During the silicone tamponade, a number of complications had occurred. Cataract had developed in 14 eyes, glaucoma in eight, and reproliferation of fibrous membranes in 12. After the removal of silicone the retina redetached in three eyes (in all cases associated with severe postoperative haemorrhage), hypotony occurred in five eyes (transiently in four) and the seven eyes remaining phakic developed a cataract. In spite of these problems the eventual visual acuities returned to the immediate post-vitrectomy levels in almost all the eyes. PMID- 8494855 TI - Cystoid macular oedema after extracapsular cataract extraction and intraocular lens implantation in diabetic patients without retinopathy. AB - Postoperative onset or aggravation of cystoid macular oedema (CMO) in diabetic patients after extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation is a frequent problem. At present little is known about the occurrence and prognosis of this complication in diabetics with no clinically detectable diabetic retinopathy (DR). Twenty five diabetic eyes (24 subjects) without DR and 45 normal eyes (44 subjects) were studied before surgery and 30, 90, 180, 360 days after ECCE and posterior chamber IOL implantation. Fluorescein angiography was performed at each examination. The frequency of angiographic CMO in the two groups was comparable 30 days after surgery but was significantly higher in diabetic eyes at 90, 180, and 360 days. This finding is probably related to an impairment of the blood-retinal barrier in diabetics. Final visual acuity, however, was similar in the two groups. PMID- 8494856 TI - Retinal detachment following anterior chamber lens implantation for the correction of ultra-high myopia in phakic eyes. AB - The development of retinal detachment is reported in three eyes, of two patients, following implantation of an anterior chamber intraocular lens (AC-IOL) in phakic eyes for the correction of ultra-high myopia. The presence of an AC-IOL may hamper the identification of retinal breaks and removal of the intraocular lens may prove necessary to improve visualisation. Shallowing of the anterior chamber may also occur during, or following, vitreoretinal surgery with risk of endothelial contact. The risks and relative contraindications of AC-IOL implantation into phakic eyes are discussed. PMID- 8494857 TI - Is the season of birth a risk factor in glaucoma? AB - Several lines of research suggest that some systemic diseases, often associated with age-related conditions, may present with enhanced prevalences owing to very early influences on human development. This paper describes an analysis of 1264 adult Caucasian patients presenting either with primary open angle or narrow angle/angle closure glaucoma on the one hand, or with age-related cataract on the other. In addition, data on cataracts and primary open angle glaucoma on 254 patients of Caribbean origin and 190 of south east Asian origin were also examined. Patients were classified with respect to sex and season of birth. These variables can play a statistically significant role in the prevalence of glaucoma, which raises the possibility that environmental influences may be involved. PMID- 8494858 TI - Clinical features of affected males with X linked ocular albinism. AB - Seventy four males affected by X linked ocular albinism (XLOA) from 19 pedigrees were examined to assess phenotypic variation and visual prognosis. Nystagmus was present in all cases except one. Best visual acuity ranged from 6/9 to 6/60; 79.7% could see 6/36 or better; most could read N5. Marked iris translucency and foveal hypoplasia were present in all cases. Posterior embryotoxon was present in 30% and dysplastic optic discs were often seen. Pigmentation of the posterior pole was associated with better visual acuity. XLOA is under-diagnosed: almost 20% of cases had been previously diagnosed as having congenital nystagmus until reviewed in this study. PMID- 8494859 TI - Ocular and vision defects in preschool children. AB - Ocular and/or vision defects are one of the commonest reasons for the referral of young children to hospital. In a survey of a birth cohort in one health district, 7.1% of children were diagnosed as having such defects by their fifth birthday; 2.1% were detected before the age of 2 years, and 5.1% between 2 and 5 years. Up to the age of 2 years, low birthweight children and those who require postnatal special care had a higher risk of having an ocular or vision defect diagnosed and were more likely to have serious visual impairment than other children. In contrast, between the ages of 2 and 5 years of age these high risk children showed no continuing increased risk of having a defect diagnosed, nor did they show any differences in the severity or type of vision defects compared with other children. Averaged over the years studied, the incidence of defects presenting to specialist eye clinics among all 2-5 year olds was 1.7%, higher than the 1.1% found for 0-2 year olds. This increase consisted primarily of children with refractive errors only. PMID- 8494860 TI - Occlusion of retinal vessels using targeted delivery of a platelet aggregating agent. AB - Local laser targeted delivery of a platelet aggregating agent to occlude retinal and choroidal vessels was evaluated in rabbits and rats. Liposomes containing adenosine diphosphate (ADP) were administered intravenously and an argon laser was used to lyse the liposomes in main retinal arteries. Control vessels were treated with the same energy of laser without administering ADP. Fluorescein angiography performed 2 weeks later showed that all the control vessels were perfused. Ninety percent of the ADP-treated arteries showed complete or partial occlusion. Successful occlusion increased with the laser energy and decreased with increasing vessel diameter. Histopathology showed that occlusion was achieved in retinal as well as choroidal vessels. The inner retina remained relatively unaffected at the treatment site but the outer retina was thermally damaged. These preliminary results suggest that targeted delivery of a platelet aggregating agent holds promise for occluding vessels in the fundus. PMID- 8494861 TI - Origin of fibronectin in epiretinal membranes of proliferative vitreoretinopathy and proliferative diabetic retinopathy. AB - Fibronectins, high molecular multifunctional glycoproteins of the extracellular matrix and plasma, have been a popular area of research in the pathogenesis of proliferative disorders of the retina. Several immunohistochemical studies have revealed that fibronectin is a major constituent of epiretinal membranes and that the cell types involved in proliferative intraocular disorders may synthesise it. However, owing to the fact that plasma and cellular fibronectin are similar in their overall structure, the origin of fibronectin in epiretinal membranes has not yet been clearly defined. In this study, we used two monoclonal antibodies: FN-3, which recognises an extra domain present in the cellular but not plasma form of fibronectin; and FN-4, which reacts with an antigenic site on both plasma and cellular fibronectin. In 37 epiretinal membranes obtained from eyes with proliferative vitreoretinopathy and proliferative diabetic retinopathy, we demonstrated the presence of cellular fibronectin, thus indicating local production. The significantly stronger and positive immunostain with FN-4 in the same specimens suggests the colocalisation of plasma fibronectin, that may be derived from the breakdown of the blood-retinal barrier and trapped in membranes during their formation. In pathological vitreous we demonstrated both types of fibronectin by western blot analysis. PMID- 8494863 TI - Primary lipid keratopathy: a morphological and biochemical assessment. PMID- 8494862 TI - Photorefractive keratectomy: implications of corneal wound healing. PMID- 8494864 TI - Serious corneal complication of 5-fluorouracil. PMID- 8494865 TI - Bilateral streptococcal corneoscleritis complicating beta irradiation induced scleral necrosis. PMID- 8494866 TI - Ocular toxocariasis in a patient with repeatedly negative ELISA titre to Toxocara canis. PMID- 8494867 TI - The trap of the displaced blind spot in automated perimetry. PMID- 8494868 TI - IgG-kappa extramedullary plasmacytoma of the conjunctiva and orbit. PMID- 8494869 TI - Perfluorocarbon liquid as a surgical adjunct in the surgical repair of stage V retinopathy of prematurity. PMID- 8494870 TI - A simple photometric detection method for HLA-DRB1 specific PCR-SSP products. PMID- 8494871 TI - HLA-DRB1 gene sequences in HLA-DR4 positive and negative patients with rheumatoid arthritis. AB - The second exon of the DRB1 gene encoding for the first domain of the HLA-DR beta 1-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected. PMID- 8494872 TI - Genetic polymorphism of human plasminogen (PLG) in a Chinese population. AB - The distribution of phenotypes and gene frequencies of the plasminogen were studied in 203 blood donors of the Han population, Chengdu, China using isoelectric focusing followed by immunofixation. The results were as follows: PLGA = 92.12%, PLGAM5 = 4.39%, PLGAB = 1.97%, PLGAB2 = 0.98%. Their gene frequencies were: PLG*A = 0.9606, PLG*M5 = 0.0246, PLG*B = 0.0099, PLG*B2 = 0.0049. This study implied that PLG*M5 might be the specific genetic marker of the Mongoloids. PMID- 8494873 TI - Lp(a) lipoprotein and HLA-DR genotype in early coronary artery disease. AB - The interest in Lp(a) lipoprotein [Lp(a)] has increased dramatically during the last few years due to the documented strong association between high Lp(a) levels and early atherosclerosis and its sequelae and the probable additional thrombogenic effect of inherited high Lp(a) levels. However, some paradoxes still remain to be solved in Lp(a) research. This pilot study was performed to test whether some criteria could be found for an association between Lp(a) levels, HLA genotype, and early coronary heart disease. If so, it could help to explain why some individuals with high Lp(a) levels get atherosclerosis while others with comparable lipid levels do not. It would also indicate that immunological processes could be involved in Lp(a) associated atherosclerosis. In this case control study the HLA-DR genotypes 13 or 17 were significantly more frequently encountered in 30 male patients with early coronary heart disease than in 30 sex and age matched healthy controls (P = 0.012). These HLA-DR specificities were especially frequent in male patients with high Lp(a) levels. The same HLA-DR genotype pattern was not seen in 30 female patients, although there was a trend towards more frequent 13a genotype. PMID- 8494874 TI - Disulfide isoform intermediates in the reoxidation of recombinant human basic fibroblast growth factor. AB - The reoxidation of human recombinant basic fibroblast growth factor was investigated following treatment of the protein with a mixture of reduced and oxidized glutathione, both in the absence and in the presence of protein disulfide isomerase. The oxidative process took place throughout the formation of two transient intermediates and yielded a stable bFGF derivative, GS2-bFGF. All of these components were separated by HPLC and accurately characterized at the molecular level by advanced mass spectrometric procedures. When the reoxidation was carried out in the presence of PDI, a 4-fold increase in the reaction rate was estimated. A mixed disulfide with a single glutathione molecule was shown to occur in the two transient intermediates, each of which has different cysteine residues involved in the linkage. The final product GS2-bFGF was structurally different from other bFGF derivatives previously described [Thompson, S. A. (1992) J. Biol. Chem. 267, 2269-2273; Caccia et al. (1992) Eur. J. Biochem. 204, 649-655]. The four cysteine residues are all involved in disulfide bridges; Cys 34 and Cys 78 are linked to exogenous glutathione, whereas Cys 91 and Cys 101 form an intramolecular S-S bridge. PMID- 8494875 TI - Interactions of basic amphiphilic peptides with dimyristoylphosphatidylcholine small unilamellar vesicles: optical, NMR, and electron microscopy studies and conformational calculations. AB - The interactions of DMPC small unilamellar vesicles with four amphiphilic polypeptides [(LKKL)n, (LRRL)n, (LKKL)4, and (YKKY)n] have been investigated by circular and infrared dichroism, turbidimetry, electron microscopy, and fluorescence, 1H, and 31P nuclear magnetic resonance spectroscopy. The main results obtained are the following: (1) Well-defined complexes are formed by the association of one amino acid residue with approximately two lipid molecules. (2) In the presence of polypeptides fusions are observed between SUVs when the molar ratio p is less than 0.05, and a clearance effect is observed when p is higher than 0.05. (3) The anchoring sites of the polypeptides on DMPC molecules are the negative phosphate groups through electrostatic interactions with the terminal NH3+ of lysine residues. (4) The polypeptides adopt an alpha-helical conformation with their axis parallel to the membrane surface. The hydrophobic part of the amphiphilic alpha helix can penetrate the outer lipid leaflet down to the C5 position. (5) Choline methyl groups are not involved in the interactions between lipid molecules and amino acid residues. (6) Phosphorus atom mobility around the P-O-glycerol bond is strongly reduced whereas that of methylene groups is progressively weakened when going up from C13 to C1. Finally, using modeling and energy calculations a model of possible Ac(LKKL)4NHEt-DMPC SUV complexes is presented. PMID- 8494876 TI - Interaction of phospholipase A2 with thioether amide containing phospholipid analogues. AB - Transferred NOE experiments have been carried out on cobra venom (Naja naja naja) phospholipase A2 (PLA2) with substrate analogues which serve as potent inhibitors. 1-(Hexylthio)-2-(hexanoylamino)-1,2-dideoxy-sn-glycero-3-pho sphoethanolamine (PE) and the corresponding phosphocholine analogue (PC) are water-soluble, short-chain, nonhydrolyzable substrate analogues which bind tightly to the enzyme. Because they are small compounds and monomeric in solution, NOEs develop inefficiently in the absence of enzyme. Thus, the PLA2/inhibitor system is ideal for analyzing transferred NOEs. The experiments are carried out under conditions that are optimal for catalysis, pH 7.5 in the presence of 2 mM CaCl2. The data show the inhibitor conformation in the catalytic site of cobra PLA2 in solution. The effect of the thioether in the sn-1 chain on the chemical shift dispersion of the methylene protons allowed for chain-specific assignments and detailed conformational analysis. Both inhibitors adopt a PLA2 bound conformation in which the end of the sn-2 chain is within 5 A of the alpha methylene of the sn-1 chain. In addition, intermolecular contact points between the inhibitor and the enzyme were identified by NOEs. PMID- 8494877 TI - Otoconin-22, the major protein of aragonitic frog otoconia, is a homolog of phospholipase A2. AB - Otoconia are composites of proteins and inorganic crystals formed in the peripheral portion of the vestibular system of vertebrates. They add mass to the extracellular otoconial membrane, thereby increasing its deflection during linear acceleration. This added mass increases the sensitivity of the underlying sensory maculae. Otoconia provide a promising system to decipher the interaction of protein and mineral during the growth and maintenance of biominerals. We have purified the major protein of the aragonitic otoconia of Xenopus laevis, which we call otoconin-22, and determined its amino acid sequence and carbohydrate composition. The 127 residues are 37% identical to the phospholipase A2 from Crotalus atrox. We propose that otoconin-22 from X. laevis is homologous to phospholipase A2 and has a similar tertiary structure. PMID- 8494878 TI - Quantitation of pre beta-HDL-dependent and nonspecific components of the total efflux of cellular cholesterol and phospholipid. AB - Both receptor-mediated and diffusional processes have been proposed as mechanisms for the efflux of cellular cholesterol to plasma. The depletion of a minor high density lipoprotein subfraction (pre beta-1-HDL) from plasma by incubation was associated with a proportional reduction in up to 58% of cholesterol and lecithin efflux from cultured fibroblasts. Pre beta-HDL-dependent efflux was blocked by protease pretreatment of the cells, while residual ("nonspecific") efflux was protease-insensitive. The whole of cholesterol efflux from blood erythrocytes was both pre beta-1-HDL-and protease-independent. These data suggest that two distinct pathways contribute to total efflux from fibroblast monolayers; one of these is directly proportional to plasma pre beta-1-HDL concentration and may involve a cell-surface protein. PMID- 8494879 TI - Activation of human plasma lipid transfer protein by apolipoproteins. AB - Activation of human plasma lipid transfer protein (LTP) by apolipoproteins was studied. Pyrenelabeled cholesteryl ester was used as a probe substrate for the transfer reaction between lipid microemulsions, with a diameter of 26 nm, of triglyceride and phosphatidylcholine, and the reaction was monitored as a change in the ratio of the peaks of monomer and excimer in the fluorescence spectrum of pyrene. The transfer of pyrene-cholesteryl ester was hardly catalyzed by highly isolated LTP in the absence of apolipoprotein unless extreme overdose of LTP was given, regardless of the presence of bovine serum albumin. Human apolipoprotein (apo) A-I and apoA-II activated the LTP reaction in a dose-dependent manner. The activation was directly proportional to the titration of the surface of the substrate lipid emulsions by the apolipoproteins when the rate was plotted against the apolipoproteins bound to the surface. Human apoE also activated the LTP reaction in the same manner. The activation by human apoC-III was also proportional to the surface-bound protein, but the rate of the transfer was lower than those with other apolipoproteins. Displacement of apoA-I by apoC-III from the lipid emulsion surface, therefore, resulted in apparent deactivation of the LTP reaction. Thus, LTP requires apolipoproteins for its activation, and the activation seems proportional to the area of the surface of the lipid substrate particles modified by apolipoproteins. ApoA-I, -A-II, and -E are more potent activators than apoC-III for cholesteryl ester transfer. PMID- 8494880 TI - Purified native subunits of bacterial luciferase are active in the bioluminescence reaction but fail to assemble into the alpha beta structure. AB - We have expressed the alpha and beta subunits of bacterial luciferase, encoded by luxA and luxB, from separate plasmids in Escherichia coli and developed an efficient purification scheme that yields many milligrams of protein of greater than 90% homogeneity. Earlier experiments showed that subunits synthesized separately assume conformations that do not assemble into the active luciferase heterodimer without prior denaturation. This observation led to the proposal that formation of the luciferase heterodimer involved interactions between intermediate conformations on the folding pathway of one or both of the subunits [Waddle, J. J., Johnston, T. C., & Baldwin, T. O. (1987) Biochemistry 26, 4917 4921]. Both of the subunits catalyze reduced flavin- and aldehyde-dependent bioluminescence reactions that are similar to that of the heterodimer in terms of reduced flavin binding affinity, aldehyde binding and inhibition, and kinetics of the overall bioluminescence reaction, but at an efficiency of about 5 x 10(-6) that of the heterodimer. Spectrophotometric analyses suggest that the structures of the individual subunits are similar to, but not identical to, the structures of the subunits in the heterodimer. Mixing of the two subunits under nondenaturing conditions did not lead to formation of the high specific activity heterodimer, even after prolonged incubation. Likewise, treatment of a stoichiometric mixture of the individual subunits with 5 M urea followed by 50 fold dilution of the urea did not yield the active heterodimer under the same conditions that yield high levels of active enzyme following denaturation of the native heterodimer [Ziegler, M. M., Goldberg, M. E., Chaffotte, A. F., & Baldwin, T. O. (1993) J. Biol. Chem. 268, 10760-10765].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494881 TI - Divalent cation binding to erythrocyte spectrin. AB - Erythrocyte spectrin dimers and separated alpha- and beta-spectrin chains bound 45Ca2+ after electrophoresis on native or sodium dodecyl sulfate-polyacrylamide gels, blotting, and 45Ca2+ overlay. Flow dialysis and equilibrium dialysis revealed two binding components: high-affinity, Ca(2+)-specific sites with kd = 4 x 10(-7) M and n = 100 +/- 20 per dimer and a low-affinity (millimolar) divalent cation component. Whereas brain spectrin had only four high-affinity sites [Wallis, C. J., Wenegieme, E. F., & Babitch, J. A. (1992) J. Biol. Chem. 267, 4333-4337], erythrocyte spectrin had 25-fold more sites per dimer. In addition to possibly modifying spectrin interactions with calcium-dependent protease and actin, as suggested by previous work on the interaction of Ca2+ with brain spectrin, the approximately two high-affinity sites per repeating segment of erythrocyte spectrin appear to stabilize a folded conformation of repeat structures indicated by an entropy increase upon binding. These data support the hypothesis that divalent cation binding to erythrocyte spectrin has become specialized to stabilize the membrane skeletal network and the cell, making them flexible but resistant to shear under the stressful conditions of blood circulation. PMID- 8494882 TI - Purification and characterization of VanR and the cytosolic domain of VanS: a two component regulatory system required for vancomycin resistance in Enterococcus faecium BM4147. AB - Resistance to the glycopeptide antibiotic vancomycin requires five genes. Two of these, vanR and vanS, have sequence homology to cytoplasmic response regulatory (VanR) and transmembrane sensory (VanS) proteins of two-component regulatory systems used to sense and transduce environmental signals. We report the overproduction and purification to homogeneity of VanR (27 kDa) and of a fusion protein of VanS (residues 95-374, the cytosolic domain) to the maltose binding protein (MBP), yielding a MBP-VanS protein of 76 kDa. The MBP-VanS fusion protein displayed an ATP-dependent autophosphorylation on a histidine residue with a rate of 0.17 min-1 and a phosphorylation stoichiometry of 10-15%. 32P-PhosphoMBP-VanS transferred the phosphoryl group to VanR. 32P-Phospho VanR showed chemical stability anticipated for an aspartyl phosphate and was relatively stable to hydrolysis (t1/2 = 10-12 h). Thus, the vancomycin resistance operon appears to have collected and specifically tailored the His kinase and Asp phosphoryl receptor of two-component signal transduction logic for sensing extracellular vancomycin and turning on structural genes, vanA and vanH, to make altered peptidoglycan structures such that vancomycin does not bind. PMID- 8494883 TI - Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes. AB - Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (delta G degree, delta H degree, and delta S degree) for the complexation of daunomycin to a series of 10 polymeric DNA duplexes. We find the resulting drug binding data to be sensitive to the base composition and sequence of the host duplex, with the binding free energies ranging from -7.5 to -10.8 kcal/mol of bound drug and the binding enthalpies ranging from +4.11 to -10.76 kcal/mol of bound drug at 25 degrees C. The smaller range in the free energy term reflects the impact of large enthalpy entropy compensations. We observe that the three synthetic duplexes which exhibit the highest daunomycin binding affinities all contain GC (or IC) base pairs as part of alternating purine/pyrimidine sequence motifs, with these high binding affinities being strongly enthalpy driven at 25 degrees C. Specific comparisons between the binding profiles for daunomycin complexation with select pairs of host duplexes lead to the following observations: (1) The presence or absence of a major-groove methyl group does not alter daunomycin binding thermodynamics. (2) The presence or absence of a minor-groove amino group does alter daunomycin binding thermodynamics. (3) Duplexes with different base compositions but identical minor-groove functionality exhibit similar daunomycin binding thermodynamics. (4) Homopolymeric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy-entropy compensations in their daunomycin binding profiles. We propose interpretations of these and other features of our thermodynamic data in terms of specific daunomycin-DNA interactions deduced from available structural data. PMID- 8494884 TI - Thermodynamics of the glucocorticoid receptor-DNA interaction: binding of wild type GR DBD to different response elements. AB - We used fluorescence spectroscopy to study the chemical equilibria between an 82 residue protein fragment containing the core conserved region of the glucocorticoid receptor DNA-binding domain (GR DBD) and a palindromic glucocorticoid response element (GRE), a consensus GRE half-site, a consensus estrogen response element (ERE) half-site, and two intermediate half-sites (GRE2 and ERE2). Equilibrium parameters were determined at 20 degrees C and buffer conditions that approximate intracellular conditions. The association constants for GR DBD binding to the GRE (5'TGTTCT3') and GRE2 (5'TGTCCT3') half-sites at 85 mM NaCl, 100 mM KCl, 2 mM MgCl2, and 20 mM Tris-HCl at pH 7.4 and low concentrations of an antioxidant and a nonionic detergent are (1.0 +/- 0.1) x 10(6) M-1 and (5.1 +/- 0.2) x 10(5) M-1, respectively. The association constants for binding to the ERE (5'TGACCT3') and ERE2 (5'TGATCT3') half-sites are < 10(5) M-1. The implications of these numbers for the specificity and affinity for the binding of the intact GR to DNA are discussed. Comparison of GR DBD binding to a GRE half-site and a palindromic GRE sequence allowed us to estimate the cooperativity parameter, omega obs = 25-50, for GR DBD binding to GRE. The thermodynamics of the GR DBD interaction with a GRE half-site were also investigated by determining the temperature dependence of the observed association constant. The nonlinear dependence in ln Kobs as a function of 1/T is consistent with a change in standard heat capacity, delta Cp degree obs = 1.0 +/- 0.2 kcal mol-1 K-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494885 TI - The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo. AB - The protein DsbA facilitates disulfide bond formation in the periplasm of Escherichia coli. It has only two cysteine residues that are separated in the sequence by two other residues and are shown to form a disulfide bond reversibly. Chemical modification studies demonstrate that only one of the cysteine residues has an accessible thiol group in the reduced protein. Equilibrium and kinetic characterization of thiol-disulfide exchange between DsbA and glutathione showed that the DsbA disulfide bond was 10(3)-fold more reactive than a normal protein disulfide. Similarly, the mixed disulfide between the accessible cysteine residue and glutathione was 10(4)-fold more reactive than normal. The overall equilibrium constant for DsbA disulfide bond formation from GSSG was only 8 x 10(-5) M. These properties indicate that disulfide-bonded DsbA is a potent oxidant and ideally suited for generating protein disulfide bonds. Disulfide bonds generally increase the stabilities of folded proteins, when the folded conformation reciprocally stabilizes the disulfide bonds. In contrast, the disulfide bond of DsbA was so unstable in the folded state that its stability increased by 4.5 +/- 0.1 kcal.mol 1 when the protein unfolded. This implies that the disulfide bond destabilizes the folded conformation of DsbA. This was confirmed by demonstrating that the reduced protein was 3.6 +/- 1.4 kcal.mol-1 more stable than that with the disulfide bond. PMID- 8494886 TI - Mutation of histidine residues in CP47 leads to destabilization of the photosystem II complex and to impairment of light energy transfer. AB - Site-directed mutagenesis has been used to change conserved histidine residues in hydrophobic regions of the photosystem II chlorophyll-binding protein CP47 in the cyanobacterium Synechocystis sp. PCC 6803. Nine mutants with one, four mutants with two, and four mutants with three His mutations in CP47 have been generated and characterized. Mutation of any one of seven different His residues to Tyr leads to slower photoautotrophic growth and apparent destabilization of the PS II complex. Mutations introduced into multiple His residues in one mutant exhibited a cumulative effect. Replacing His by Asn leads to a much smaller effect than observed upon mutation to Tyr. This is consistent with the hypothesis that the mutated His residues are chlorophyll ligands: Asn can substitute as chlorophyll ligand, whereas Tyr cannot. Further evidence supporting a role of the mutated His residues in chlorophyll binding comes from measurements of the light intensity needed to half-saturate oxygen evolution. All His mutants with impaired PS II function needed higher light intensities for half-saturation than wild type. A possible explanation for this decrease in antenna efficiency in the mutants is a loss of the Mg in the chlorophyll due to a loss of the fifth ligand, and thus the formation of a pheophytin molecule in the antenna. We conclude that conserved His residues in hydrophobic regions of CP47 indeed are chlorophyll ligands and that these ligands are important for PS II stability as well as efficient antenna function. PMID- 8494887 TI - Differences in the binding affinities of dimeric concanavalin A (including acetyl and succinyl derivatives) and tetrameric concanavalin A with large oligomannose type glycopeptides. AB - Dimeric derivatives of concanavalin A (Con A) such as acetyl- and succinyl-Con A have been used for years as probes of cellular membranes. The altered binding and biological activities of these derivatives relative to native tetrameric Con A have generally been attributed to their reduced valence. However, the present study shows that acetyl- and succinyl-Con A possess lower affinities than tetrameric Con A toward certain oligomannose-type glycopeptides which are found on the surface of cells. It has previously been shown that native tetrameric Con A possesses 5-30-fold enhanced affinities toward Man7-Man9 oligomannose-type glycopeptides, respectively, relative to Man5 and Man6 oligomannose-type glycopeptides [Bhattacharyya, L., & Brewer, C. F. (1989) Eur. J. Biochem. 178, 721-726]. Using titration microcalorimetry and hemagglutination inhibition measurements, methyl alpha-D-mannopyranoside, methyl 3,6-di-O-(alpha-D mannopyranosyl)-alpha-D-mannopyranoside (which binds with about 60-fold higher affinity than methyl alpha-D-mannopyranoside and is the major Con A binding epitope on oligomannose-type carbohydrates), and a Man5 oligomannose-type oligosaccharide are shown to bind to underivatized dimeric Con A at pH 5.2 and acetyl- and succinyl-Con A at pH 7.2 with affinities equal to those of native tetrameric Con A. However, a mixture of Man7 and Man8 glycopeptides and a Man9 oligomannose-type glycopeptide were shown to bind to underivatized dimeric Con A and acetyl- and succinyl-Con A with affinities only about 2-fold higher than the Man5 oligosaccharide, in contrast to the higher affinities of native tetrameric Con A for these carbohydrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494888 TI - Human plasma cholesteryl ester transfer protein consists of a mixture of two forms reflecting variable glycosylation at asparagine 341. AB - Plasma cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids and phospholipids between the plasma lipoproteins. The deduced M(r) of the CETP polypeptide from the cDNA is 53,000, but in sodium dodecyl sulfate (SDS) gels plasma CETP appears as a broad band containing two different molecular forms of M(r) 65,000-71,000. The purpose of this study was to see if variable N-linked glycosylation could explain the microheterogeneity of CETP. Recombinant CETP (rCETP), derived from stable expression of the CETP cDNA in Chinese hamster ovary (CHO) cells, appeared as a protein doublet comparable to plasma CETP. Digestion of plasma or rCETP with N-glycosidase F (glyco F, to remove N-linked carbohydrates) resulted in the formation of a lower M(r) doublet in which the bottom band approximated the M(r) of the CETP polypeptide. Metabolic labeling of the rCETP with [3H]mannose and [3H]glucosamine, followed by digestion with glyco F, suggested that the top band of the doublet contained residual N-linked carbohydrates resistant to glyco F digestion. To explore this hypothesis further, each of the four potential N-linked glycosylation sites of CETP (at amino acid positions 88, 240, 341, and 396) was eliminated by mutagenesis of asparagine to glutamine. The wild-type (WT) and mutant CETP cDNAs were transiently expressed in COS-7 cells. Each mutant CETP showed a lower M(r) than WT, indicating that all four sites were occupied by N-linked carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494889 TI - Metallothionein detoxification function is impaired by replacement of both conserved lysines with glutamines in the hinge between the two domains. AB - Mammalian metallothioneins (MTs) possess eight highly conserved lysine residues, two of which constitute the hinge between two metal binding domains. By site directed mutagenesis and recombinant DNA techniques, we replaced the interdomain lysines in Chinese hamster ovary MT2 with all possible combinations of glutamic acid and/or glutamine. The resultant MTs were expressed and assayed for detoxification function in a transformed yeast system. Results showed that these mutant MTs, like the native protein, bound seven atoms of divalent metal per molecule and conferred cadmium resistance to a metal-sensitive yeast host. Replacement of one or both of the lysines in the interdomain region was inconsequential to the structure and function of MT, unless both substituted residues were uncharged. When both lysines were replaced by glutamine (K30,31Q), a reduction in the ability of MT to protect yeast transformants against otherwise toxic levels of cadmium was observed. This diminished metal detoxification capacity was due to a decrease in the steady-state level of MT. These results suggest that at least one charged amino acid must be present in the hinge for the proper expression of MT. PMID- 8494890 TI - Serine92 (F7) contributes to the control of heme reactivity and stability in myoglobin. AB - The effects of mutation of the conserved serine92 residue to alanine, valine, and leucine in pig myoglobin have been determined. In myoglobin crystal structures, the hydroxyl group of serine92 is within hydrogen-bonding distance of the N delta H of histidine93, whose N epsilon coordinates the iron atom of the heme prosthetic group. The association equilibrium constants of the ferrous forms of the mutant myoglobins for O2, CO, and methyl and ethyl isocyanide are increased 1.3-13-fold relative to the wild-type protein. The rates of azide association with the mutant ferric proteins at neutral pH are decreased by factors of 2-5 consistent with an increased affinity for the iron-bound water molecule which must be displaced. The dissociation rates for azide appear to be decreased 4-10 fold, suggesting that the affinity of the mutant proteins for this ligand is also higher. Thus, the overall affinities are increased regardless of the chemical nature of the liganded species, indicating that the reactivity of the heme iron itself has been raised. Time courses for association of methyl and ethyl isocyanide at high concentrations show fast and slow phases in which the absorbance at 445 nm drops and then rises, respectively. Comparison of these traces with spectra following the reaction of isocyanide ligands with chelated proton heme in soap micelles indicates that the slow phase is associated with the breaking of the iron-proximal histidine bond and the binding of a second isocyanide species in the proximal heme pocket.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494891 TI - Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase. AB - Modification of class III alcohol dehydrogenase (chi chi-ADH) with phenylglyoxal eliminates fatty acid activation by pentanoate and octanoate and concomitantly increases specific activity toward ethanol and 3-methylcrotyl alcohol 2-3-fold. In contrast, chemical modification decreases activity toward S (hydroxymethyl)glutathione (FDH activity) and 12-hydroxydodecanoic acid by increasing Km, pointing to a role for arginine in binding anionic substrates. Modification with [7-14C]phenylglyoxal indicates that only one arginine residue per subunit is modified. Sequence analysis of tryptic peptides indicates that Arg 115 is modified. Site-directed mutation of this residue to alanine eliminates both fatty acid activation and FDH activity, thus confirming the identity of the modified residue and its function. These results account in part for the unique specificity of chi chi-ADH relative to other human ADH isozymes. PMID- 8494892 TI - Interaction of barnase with its polypeptide inhibitor barstar studied by protein engineering. AB - Barnase, an extracellular ribonuclease of Bacillus amyloliquefaciens, forms a very tight complex with its intracellular polypeptide inhibitor barstar. At pH 8, the values for the rate constants k1 (association) and k-1 (dissociation) are 6.0 x 10(8) s-1 M-1 and 8.0 x 10(-6) s-1, respectively. The value of Ki, the dissociation constant of barstar and barnase, calculated from the ratio k-1/k1 is 1.3 x 10(-14) M, which corresponds to a delta G of -18.9 kcal/mol at 25 degrees C. The dissociation constant increases with decreasing pH according to the ionization of an acid in free barnase of pKa 6.4, with very weak, if any, binding to the protonated form. This pH dependence for dissociation of the complex can be attributed almost entirely to residue His102 in barnase, as determined by a His102-->Ala mutation. Analysis of the pH dependence of the kinetic constants indicates that binding is, at least, a two-step process. The first, and rate determining, step is association at close to the diffusion-controlled rate. There is then the precise docking of the complex. The value of Ki increases to 2.4 x 10(-11) M in the presence of 500 mM NaCl, and to 1.6 x 10(-11) M at pH 5 (100 mM NaCl). The binding site of barstar on barnase was mapped by measuring the values of Ki for a broad range of site-specific mutants of barnase. Mutagenesis of residues Lys27, Arg59, Arg87, and His102 to Ala increases the values of Ki by a factor of 10(4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494893 TI - Acid-base catalytic mechanism of dihydropyrimidinase from pH studies. AB - The pH dependence of kinetic parameters and solvent deuterium isotope effects have been used to probe the mechanism of the dihydropyrimidinase from the liver of pig and calf. The V/K for 5,6-dihydrouracil (DHU) (or the alternative substrate glutarimide) measured with either the native zinc or cadmium substituted enzymes decreases at both low and high pH giving pK values of about 7.5-8 and 9-10. The low pK value observed in V is perturbed significantly to lower pH (approximately 6), and the high pK is not observed. The binding of glutarate monoamide is optimum when the group with a pK of 7.7 is protonated, and this same group must be protonated for the reverse reaction, that is, formation of DHU from N-carbamoyl-beta-alanine. These data are consistent with a general base mechanism and in addition suggest that the enzyme is present initially with a water bound to the active site zinc. The enzymic general base with a pK of 7.5 8 is required to activate water for nucleophilic attack on the C-4 of 5,6 dihydrouracil which is directly coordinated to the active site zinc. The second group with a pK of 9-10 likely reflects Zn-water ionization of the free enzyme. The water bound to the active site Zn is displaced by reactant binding, and thus the pK of 9-10 is not observed in the V profile. Solvent deuterium isotope effects are near unity on the V/K for the natural substrate 5,6-dihydrouracil, but a finite effect of 1.6 is observed on V.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494894 TI - Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases. AB - We have isolated cDNAs encoding the alpha and beta subunits of human farnesyl protein transferase (FPTase). The proteins encoded by these two cDNAs are 93-95% identical to the corresponding subunits of bovine and rat FPTase and show regions of homology with proteins encoded by Saccharomyces cerevisiae prenyl-protein transferase genes. Human FPTase expressed in Escherichia coli from a translationally coupled operon had kinetic properties similar to those of FPTase isolated from bovine brain. Examination of farnesyl diphosphate binding indicated that while neither individual subunit was capable of isoprenoid binding, a radiolabeled farnesyl diphosphate analog could be specifically photo-cross-linked to the beta subunit of FPTase holoenzyme. To further analyze subunit structure function and to detect functional similarities with yeast prenyl-protein transferases (FPTase and two geranylgeranyl-protein transferases), amino acid changes homologous to those found in mutant yeast prenyl-protein transferase subunits were made in the subunits of human FPTase. Substitutions in either the alpha or beta subunits that decrease the activity of yeast prenyl-protein transferases were also observed to impair human FPTase. Kinetic analyses showed that these mutant human FPTases have Km and kcat values that are altered with respect to wild-type human FPTase. PMID- 8494896 TI - Spectral and kinetic studies of imine product formation in the oxidation of p (N,N-dimethylamino)benzylamine analogues by monoamine oxidase B. AB - The oxidative deamination of p-(N,N-dimethylamino)benzylamine and N-methyl-p-(N,N dimethylamino)benzylamine by bovine liver monoamine oxidase B has been investigated by absorption spectral, steady-state, and stopped-flow kinetic studies. An absorbing intermediate with a maximum at 390 nm is observed with either analogue in turnover experiments at neutral pH and is identified as due to the formation of protonated imine as the initial product. p-(N,N Dimethylamino)benzaldehyde is the final product formed from either substrate analogue. Anaerobic stopped-flow measurements show N-methyl-p-(N,N dimethylamino)benzylamine to reduce enzyme-bound flavin with a limiting rate of 1.8 s-1 concurrent with the appearance of a 390-nm absorption due to protonated imine product with a limiting rate of 1.7 s-1. Both observed rates are somewhat faster than catalytic turnover (1.5 s-1). Under anaerobic conditions, the decay of protonated N-methyl-p-(N,N-dimethylamino)benzenimine is much slower than turnover (k = 4.8 x 10(4) s-1). p-(N,N-Dimethylamino)benzylamine reduces the enzyme with a limiting rate of 2.1 s-1, which is faster than catalytic turnover (1.2 s-1). Protonated imine formation is also observed with this substrate with an apparent limiting rate of 1.3 s-1. The decay of the protonated p-(N,N dimethylamino)benzenimine absorbance is slower than catalytic turnover but faster than the rate of aldehyde formation under anaerobic conditions. Deuterium kinetic isotope effect values of approximately 10 are observed both for flavin reduction and for protonated imine formation. No isotope effect is observed for the rate of imine decay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494895 TI - Imidazole glycerol phosphate synthase: the glutamine amidotransferase in histidine biosynthesis. AB - Two proteins essential for the biosynthesis of the amino acid histidine in Escherichia coli have been overexpressed and purified to apparent homogeneity. The protein encoded by the hisF gene has an ammonia-dependent activity that results in the conversion of the biosynthetic intermediate N1-[(5' phosphoribulosyl)formimino]-5-aminoimidazole-4- carboxamide ribonucleotide (PRFAR) to imidazole glycerol phosphate (IGP) and 5-aminoimidazole-4-carboxamido 1-beta-D- ribofuranosyl 5'-monophosphate (AICAR). The second protein encoded by the hisH gene exhibits no detectable catalytic properties with biosynthetic intermediate PRFAR, glutamine, or ammonia. In combination, the proteins are capable of a stoichiometric conversion of glutamine and PRFAR to form AICAR, IGP, and glutamate. Neither protein alone is capable of mediating a conversion of the nucleotide substrate to a free metabolic intermediate. The HisH and HisF proteins form a stable 1:1 dimeric complex that constitutes the IGP synthase holoenzyme. Steady-state kinetic parameters for the holoenzyme indicate that glutamine is a more efficient substrate relative to ammonium ion by a factor of 10(3). The HisF subunit will support an ammonia-dependent reaction with a turnover number similar to that of the holoenzyme with glutamine. The glutaminase activity for the holoenzyme is 0.8% of that in the presence of the nucleotide substrate PRFAR. There are critical subunit interactions that mediate the catalytic properties for glutamine hydrolysis. The catalytic turnover of glutamine can be increased up to 37-fold by the addition of either the product IGP or the biosynthetic precursor N1-[(5'-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (5'-ProFAR). The mechanistic significance of this glutaminase activity compared to other trpG type glutamine amidotransferases is discussed. PMID- 8494897 TI - Oxidative refolding of insulin-like growth factor 1 yields two products of similar thermodynamic stability: a bifurcating protein-folding pathway. AB - Can one protein sequence encode two structures? Oxidative folding of human insulin-like growth factor 1 (IGF-1), a globular protein of 70 residues, is shown to yield two products of similar thermodynamic stability. This observation is of particular interest in light of the recent demonstration that two of the three disulfide bonds in native IGF-1 rearrange in the presence of dithiothreitol [Hober, S., et al. (1992) Biochemistry 31, 1749-1756]. Kinetics of the IGF-1 folding pathway were monitored by high-performance liquid chromatography (rp HPLC). Disulfide-pairing schemes of intermediates and products were established by peptide mapping. Two disulfide isomers were obtained as products: one with native insulin-like pairing [6-48; 18-61; 47-52] (designated native IGF-1; 60% yield) and the other with alternative pairing [6-47; 18-61; 48-52] (designated IGF-swap; 40% yield). The predominant early intermediate contains the single disulfide 18-61, which is shared in common by the two products. Relative yields of native IGF-1 and IGF-swap are independent of protein concentration under dilute conditions. In the absence of an added thiol reagent, each isomer is stable indefinitely at neutral pH; in the presence of an added thiol reagent, the two isomers interconvert with an Arrhenius activation barrier of 12 kcal/mol. Interconversion does not require complete reduction and yields the same ratio of products as initial folding, demonstrating thermodynamic control. Spectroscopic studies using circular dichroism (CD), infrared spectroscopy (FTIR), two dimensional 1H-NMR (2D-NMR), and photochemical dynamic nuclear polarization (photo-CIDNP) suggest that IGF-1 and IGF-swap adopt similar secondary structures but distinct tertiary folds. Implications of these observations for understanding the topology of protein-folding pathways are discussed. PMID- 8494898 TI - Role of native disulfide bonds in the structure and activity of insulin-like growth factor 1: genetic models of protein-folding intermediates. AB - Insulin and insulin-related proteins contain three motif-specific disulfide bonds. Here we examine the role of these disulfide bonds in the folding and function of one family member, human insulin-like growth factor 1 (IGF-1). Analogues containing pariwise Cys-->Ser or Cys-->Ala substitutions were expressed in Escherichia coli, purified, and analyzed with respect to receptor-binding, solution structure, and thermodynamic stability. An analogue lacking all three disulfide bonds (designated des-Cys-IGF-1) is inactive and unfolded. Introduction of the [18-61] disulfide bond, previously shown to occur in an early intermediate in oxidative refolding [Miller, J. A., Owers-Narhi, L., Hua, Q. X., Rosenfeld, R., Arakawa, T., Rohde, M., Prestrelski, S., Lauren, S., S. Stoney, K. S., Tsai, L., & Weiss, M. A. (1993) Biochemistry (preceding paper in this issue)], results in a compact partially folded state with low but significant biological activity. Additional but incomplete structural organization and biological activity are observed following introduction of either the [6-48] or the [47-52] disulfide bonds. Native function, structure, and stability require the presence of all three disulfide bonds. These analogues provide genetic models of IGF-1 protein folding intermediates. Their characterization suggests that bifurcation of the IGF-1 folding pathway reflects alternative late steps in the folding of a molten globule intermediate. PMID- 8494899 TI - Effects of amino acid substitutions on the pressure denaturation of staphylococcal nuclease as monitored by fluorescence and nuclear magnetic resonance spectroscopy. AB - In the present study we have used high hydrostatic pressure coupled with either time-resolved and steady-state fluorescence or NMR spectroscopy in order to investigate the effects of amino acid substitutions on the high-pressure denaturation properties of staphylococcal nuclease. This protein has been shown previously to be structurally heterogeneous in its native state. On the NMR time scale, four distinct interconverting conformational forms arise from the population of both cis and trans Xaa-Pro peptide bonds (His46-Pro47 and Lys116 Pro117) [Evans et al. (1989) Biochemistry 28, 362; Loh et al. (1991) in Techniques in Protein Chemistry II, pp 275-282, Academic Press, New York]. Mutations in the protein sequence have been shown to change the distribution among the various forms [Alexandrescu et al. (1989) Biochemistry 28, 204; Alexandrescu et al. (1990) Biochemistry 29, 4516]. Time-resolved fluorescence on a series of mutants with altered equilibria for cis/trans isomerism about the 116 117 peptide bond did not reveal any simple relationship between the position of the cis/trans equilibrium in the folded state and the heterogeneity of the fluorescence decay. However, the specific dynamic properties of each mutant, as revealed by time-resolved fluorescence, do appear to be correlated with their partial molar volume changes of denaturation. A striking finding is that mutation of either (or both) of the prolines that exhibits structural heterogeneity to glycine greatly alters the stability of the protein to pressure. These mutations also result in decreased chain mobility as assessed by time-resolved fluorescence. It appears that packing defects, which allow for peptide bond cis/trans heterogeneity in the wild-type protein, are removed by the Pro-->Gly substitutions. PMID- 8494900 TI - Mechanism of the oxidation reaction of deoxyhemoglobin as studied by isolation of the intermediates suggests tertiary structure dependent cooperativity. AB - The intermediates in the oxidation of deoxyhemoglobin by ferricyanide in 0.1 M KCl, at 20 degrees C and three pH values, were studied by cryogenic techniques. Data analysis was carried out according to a simple four rate constant model, ignoring the functional heterogeneity of the subunits, to simulate the time courses of the oxidation reaction, as studied by the stopped-flow technique [Antonini et al., (1965) Biochemistry 4, 345], which show anticooperativity at neutral pH and cooperativity at alkaline pH. Data analysis according to a 12 rate constant model indicated that the rate of oxidation of the beta subunit in the first oxidation reaction was 4 times faster than the rate of oxidation of the alpha subunit at pH 6.2 and 12 times faster at pH 8.5. The reactions involving the alpha subunit were noncooperative except for the last oxidation step at acid and neutral pH, but were cooperative at alkaline pH. The reactions involving the beta subunit were partly noncooperative and partly anticooperative. These complex mechanistic patterns suggest that a simple two-state model requiring the concerted transition of the tertiary structures of the subunits from the T to the R conformation is not adequate to interpret the oxidation reaction and that tertiary structures contribute, positively and negatively, to cooperativity. A structural hypothesis is suggested to explain the difference in the reactivities of the alpha and beta subunits. PMID- 8494902 TI - Binding of guanosine and 3' splice site analogues to a group I ribozyme: interactions with functional groups of guanosine and with additional nucleotides. AB - Dissociation constants, Kd, were measured by equilibrium dialysis at 5 degrees C for a series of substrates binding to the L-21 ScaI ribozyme derived from the Tetrahymena thermophila self-splicing large subunit (LSU) ribosomal RNA intron. These substrates are analogues for the 3' exon splice site, the cyclization site, and the exogenous G that initiates group I splicing. UCG has a Kd of 17 microM. Lengthening the substrate to GUCG and GGUCG enhances binding but by less than expected from potential base pairing. Functional groups on the 3'-terminal G of GUCG were replaced with H to test their effect on binding. GUC(2'dG) binds slightly tighter than the all-ribose molecule but shows no reactivity as a substrate. GUC(3'dG) binds weaker than GUCG. Inosine and 2-aminopurine ribonucleoside at the 3' position weaken binding by 16- and 26-fold, respectively, but both tetramers are reactive. Thus hydrogen bonds to Watson Crick pairing positions of the 3'G of GUCG contribute 1-2 kcal/mol to the free energy change for binding. Similar results are found in comparisons of UCG with UC(2'dG), UC(3'dG), and UCI. The nonreactive substrate GUCdGA includes a phosphodiester bond 3' to the guanosine that is the site of chemistry for the all ribose substrate GUCGA; GUCdGA binds 50 times more weakly than GUCdG. A similar result is obtained for GUCdGU. Competition experiments show that guanosine and guanosine 5'-monophosphate bind with dissociation constants of about 0.9 mM. The monomers 2'dG and 3'dG have Kd's of 0.5 and > or = 3 mM, respectively. This suggests that sugar pucker and/or interactions with hydroxyl groups affect binding. Implications for ribozyme catalysis, splicing, cyclization, and design of antisense oligomers are discussed. PMID- 8494901 TI - tRNA-guanine transglycosylase from Escherichia coli: gross tRNA structural requirements for recognition. AB - tRNA-guanine transglycosylase (TGT) is the enzyme responsible for the post transcriptional modification of specific tRNAs (those for Asn, Asp, His, and Tyr) with the hypermodified base, queuine. In Escherichia coli this enzyme catalyzes the exchange of guanine-34 in the anticodon with preQ1, which is subsequently further modified to queuine. There is evidence that such hypermodified tRNA molecules may play a role in the control of cell proliferation and differentiation. In order to perform detailed, in vitro mechanistic studies and to probe the tRNA-enzyme interaction, we have generated unmodified E. coli tRNA(Tyr) and truncated analogues using an in vitro RNA synthesis system suggested by Milligan and Uhlenbeck [Milligan, J. F., & Uhlenbeck, O. C. (1989) Methods Enzymol. 180, 51-62]. From this system we have generated three tRNA analogues totally devoid of any post-transcriptional modifications. In order to compare the unmodified tRNA with the true physiological substrate for TGT, that is, tRNA that contains all modified bases except queuine, we have isolated E. coli tRNA(Tyr) from an overexpressing clone in a TGT-deficient strain of E. coli. We report here that unmodified, full-length tRNA(Tyr) serves as a substrate for TGT with kinetic parameters that are, within experimental error, the same as those for in vivo isolated tRNA(Tyr). This indicates that other post transcriptional modifications have negligible effects upon TGT recognition of tRNA. A 17-base oligoribonucleotide, corresponding to the anticodon loop and stem, is also a substrate for TGT with only a 20-fold loss in Vmax/KM, versus the full-length tRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494903 TI - A single-stranded DNA binding protein from Drosophila melanogaster: characterization of the heterotrimeric protein and its interaction with single stranded DNA. AB - We describe the purification to near homogeneity of a single-stranded DNA binding protein from 0-18-h embryos of Drosophila melanogaster. Drosophila SSB (D-SSB) is a heterotrimer with subunits of molecular weight of 70,000, 30,000, and 8000. It has a Stokes radius of 48.6 +/- 2 A and s20,w = 5.0 +/- 0.2 S. The interaction of D-SSB with ssDNA was examined by the quenching of intrinsic protein fluorescence. The binding site size was determined to be n = 22 +/- 4 nucleotides with a maximum quenching Qm = 35 +/- 3%. Equilibrium titrations indicate that D-SSB binds with low cooperativity, omega = 10-300, and high apparent affinity, K omega = (0.7-5) x 10(7) M-1, at 225 mM NaCl. Sedimentation of D-SSB bound to small oligonucleotides demonstrates that D-SSB does not require protein association for binding. D-SSB stimulates the extent and processivity of DNA synthesis of its cognate DNA polymerase alpha. On the basis of these properties, we conclude that D-SSB is the Drosophila cognate of the human and yeast SSB/RP-A proteins. PMID- 8494904 TI - Dissection of a class II tRNA synthetase: determinants for minihelix recognition are tightly associated with domain for amino acid activation. AB - The ten class II aminoacyl-tRNA synthetases are large homo- and hetero-oligomeric proteins that share three conserved sequence motifs. Within this class, Escherichia coli alanyl-tRNA synthetase is the only homotetramer and is comprised of subunits of 875 amino acids. The enzyme aminoacylates sequence-specific RNA oligonucleotides that recreate as few as four base pairs of the acceptor stem of tRNA(Ala). A monomeric 461 amino acid N-terminal fragment (461N) was previously shown to have full adenylate synthesis activity. However, fragment 461N has significant, but reduced, efficiency of charging of tRNA(Ala), when compared to native enzyme [Ho, C., Jasin, M., & Schimmel, P. (1985) Science 229, 389-393]. We show here that, in contrast, the fragment and the native enzyme aminoacylate a 12 base pair acceptor-T psi C stem minihelix and a four base pair RNA tetraloop with the same efficiency. We also show that fragment 461N makes footprint contacts both on and outside the acceptor helix of bound tRNA(Ala). With one possible exception, the contacts observed with fragment 461N are identical to those seen with the native enzyme. In spite of contacts outside the acceptor helix, fragment 461N charges the native tRNA, minihelix, and tetraloop with similar efficiency. Thus, all minihelix contacts required for activation for charging are tightly associated with the adenylate synthesis domain and, at least in the fragment, are not influenced by additional RNA-protein contacts outside the minihelix domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8494905 TI - Neuropathology, cell biology, and newer diagnostic methods. AB - Recent publications emphasized the correlation between molecular events in brain tumors and clinical outcome. Alterations in tumor-suppressor genes, growth factors, and enzyme systems have been previously described in gliomas; the relationships between these various changes and tumor grade, growth rate, and response to therapy are subjects of current investigations. Loss of genetic heterozygosity on chromosomes 10 and 17p, amplification and rearrangement of the epidermal growth factor receptor gene, express ion of its protein product, and changes in chromosomes 9, 19, and the enzyme system protein kinase C are the specific molecular events that were compared. Changes in chromosome 22 were correlated with histologic features of meningioma. Various methods of measuring tumor cell proliferation (proliferating cell nuclear antigen, bromodeoxyuridine, Ki-67, nucleolar organizer regions, and DNA flow cytometry) are being compared with each other and correlated with clinical outcome in an attempt to validate these methods and to discover the most relevant one. More recently described tumor types continue to be characterized using standard techniques and some of these newer methods. Neurocytoma has been morphologically and immunochemically defined as a neuronal neoplasm, but determination of the full compass of its clinical behavior and position in the continuum of cerebral neuronal tumors awaits additional studies. PMID- 8494906 TI - Surgery of supratentorial tumors. AB - Neurosurgery may be the ultimate treatment of benign tumors, eg, certain meningiomas and acoustic neurinomas; however, for invasive and malignant tumors, it is just another part in a multimodality approach coupled with radiotherapy, chemotherapy, and possibly immunotherapy. Still heading for more efficiency, new surgical techniques and aids have been developed. Their multiplicity and precision should encourage the neurosurgeon to even more carefully plan the type of surgery by a thorough preoperative evaluation. Preoperative management now not only assesses the size and the extent of the tumor but tries to find hints of its degree of malignancy to understand the perilesional edema and to guide the surgeon's hand. Although surgical approaches have been improved over the past years by the introduction of microsurgery, the ultrasonic aspirator, laser, and perioperative ultrasound, computer-assisted stereotactic neuronavigation seems to be the major novelty, and its future developments may prove to be of great medical value. Finally, the postoperative evaluation of the patient also benefits from new standards in neuroimaging and radionuclide investigations, allowing better estimation of residual tumor and early diagnosis of recurrence. PMID- 8494907 TI - Chemotherapy and immunotherapy in adult malignant gliomas. AB - This review summarizes papers published during 1991 and 1992. The poor results obtained in the postneurosurgical treatment of gliomas led researchers to pursue attempts to try to overcome glioma cell resistance. The intra-arterial route was explored in several phase II studies with new drugs and even immunoconjugates; rates of response between 30% to 60% were obtained. New drugs (fotemustine, eflornithine, and estramustine) or combined protocols planned to circumvent chemoresistance were tested and showed some efficiency with moderate toxicity, enlarging the number of drugs available against malignant gliomas. On the contrary, two retrospective analyses warned about the risk of reduction of median time to survival due to adjuvant chemotherapy in anaplastic astrocytomas; this finding, if confirmed, would suggest to defer chemotherapy at the time of recurrence in this type of glial tumor. Immunobiologic therapies as immunomodifiers, immunoconjugates, or cytotoxic lymphocyte-activated killer cells and tumor-infiltrating lymphocytes were tested and allowed some responses to be obtained. In young children, chemotherapy regimens were found to be efficient in malignant plexus choroid carcinomas and low-grade gliomas, allowing radiation therapy to be deferred. Many studies were methodologically unsatisfactory because of uncertain pathology grouping, noncompliance to initial protocols, or too small populations of patients. PMID- 8494908 TI - Epidemiology, cytogenetics, and molecular biology of brain tumors. AB - The incidence of primary brain tumors has increased dramatically among elderly North Americans during the past two decades. Numerous chromosomal abnormalities have been associated with these tumors; various subsets of these abnormalities are specific to certain types of brain tumors. Astrocytic gliomas may exhibit losses of genetic information from chromosomes 9p, 10q, 11p, 13q, 17p, or 22. Mutations of the p53 gene are found mostly in the malignant astrocytic forms and have been linked to malignant tumor transformation and progression. Functional and structural abnormalities of the neurofibromatosis 1 (NF1) gene and overexpression of the epidermal growth factor receptor have been associated with expression of the malignant glioma phenotype. Other less clearly defined abnormalities in astrocytomas include mutations of the retinoblastoma (RB) gene and overexpression of platelet-derived growth factor; transforming growth factor alpha and -beta; the c-erb B-1, c-myc, ras, c-fos, and ros oncogenes; and insulin like growth factor I and II. In other glioma tumors, p53 mutations are either infrequent, as in oligodendrogliomas, or absent, as in ependymomas. Occasionally, medulloblastomas exhibit p53 mutations and loss of genetic information from chromosomes 6q and 16q or expression of the c-erb B-2 oncogene. Loss of heterozygosity in chromosome 22 is the most frequent event in meningiomas, suggesting the presence of a tumor-suppressor gene in this chromosome. PMID- 8494909 TI - Carcinogenesis, markers, staging, and prognosis of head and neck cancer. AB - The integration of basic science perspectives into clinical head and neck oncology remains a priority. During this past year, we have witnessed initial results from many laboratories regarding p53 expression. Point mutations in the p53 gene have been identified and related to carcinogen exposure. Abnormalities in p53 have been identified in not only intra-epithelia neoplasia but also normal mucosa, suggesting an early genetic event. The ability to identify early genetic abnormalities will allow for earlier therapeutic strategies. The integration of basic science advances will likewise lead to improved prognostication and ultimately to improved staging. Prototypical of this process is DNA cytometric analysis. Reports in the past year have made use of integrated image analysis technology to measure both nuclear DNA content and nuclear volume. The incorporation of these measurements provided prognostic information beyond current staging techniques. Finally, the understanding of genetic alterations is beginning to carry with it potential therapeutic implications. Chromosome alterations at 11q13 may involve expression of several genes, including glutathione S-transferase (GST). Investigators have noted that the expression of this gene, as reflected in circulating GST blood levels, may predict chemotherapeutic responsiveness. Despite these basic science advances, population studies revealed that head and neck cancer mortality is increasing in certain segments of our society, eg, black American men. New strategies are required if improved survival from head and neck cancer is to be realized. PMID- 8494910 TI - Pathology of squamous carcinomas of the head and neck. AB - Recent publications dealing with the pathology of squamous carcinomas of the head and neck have been critically reviewed with particular reference to potential prognostic factors and improved methods for identifying nodal metastases. The topics covered include cytophotometry and proliferative patterns, molecular biology (EGFR and p53 genes), cell adhesion molecules (E cadherin), and combined radiologic and pathologic approaches to detect small volume metastases in cervical lymph nodes. PMID- 8494911 TI - Surgery for head and neck cancer. AB - During the past year, several areas of head and neck surgery have had notable refinements and advancements. In the area of early laryngeal cancer, the complementary roles of radiation therapy and surgery have been discussed, as well as refinements in endoscopic laser techniques. Issues of the incidence of nodal metastasis and the role of in-continuity versus discontinuous neck dissection in oral and pharyngeal carcinoma have been considered. Rehabilitation techniques following treatment of oral cancer using free microvascular sensate flap reconstructions have been presented. The role of free jejunal interposition and gastric pull-up for reconstruction in hypopharyngeal cancer have been discussed, as well as their compatibility with postoperative radiotherapy. Finally, the concepts for treatment of neck nodal metastases have been discussed in relation to the roles of radiotherapy, radical neck dissection, and modified neck dissection. PMID- 8494912 TI - Chemotherapy and combined modality therapy in head and neck cancer. AB - Chemotherapy for head and neck cancer is being actively investigated. Trials of cisplatin, infusional fluorouracil, and other new agents highlight the need for better therapies for patients with recurrent disease. Induction chemotherapy, concomitant chemoradiotherapy, and rapid-sequence combined therapy have been shown to be feasible treatments with encouraging results. Rapidly alternating chemoradiotherapy has been shown to result in a survival benefit compared with radiotherapy alone. Biologic therapy, including interferon and interleukin-2, also merits future evaluation in clinical trials. PMID- 8494913 TI - Salivary gland tumors. AB - Salivary gland cancers continue to pose both diagnostic and treatment dilemmas. Over the past year, a great deal has been written concerning salivary gland tumors in children, fine needle aspiration for salivary gland neoplasms, prognostic factors, and pathologic evaluation and treatment. Some of the more important findings include imaging studies and approaches to the human immunodeficiency virus-positive patient with parotid enlargement, the molecular biology of salivary cancer, and the pitfalls of fine needle aspiration cytology. The necessity of facial nerve sacrifice in parotid surgery for malignancy is debated, and the classification of tumors is clarified. PMID- 8494914 TI - Renal cell carcinoma. AB - The past year has been an exciting one for progress in our understanding of renal cell carcinoma. Substantial insight has been gained into our understanding of the immune system and how it both interacts with and is affected by renal cell carcinoma. The roles of the interferons and interleukins and the patients who are most likely to benefit from these agents have been better defined. Some new biologic markers of renal cell carcinoma have been described that may prove useful both prognostically and therapeutically. Lastly, advancement has been made in our basic understanding of the molecular aspects of renal cell carcinoma, which hold promise for better targeted, less toxic, and hopefully more effective treatment of patients with advanced disease. PMID- 8494915 TI - Incorporating tumor biology into therapy for prostate cancer. AB - Prostate cancer remains the most common and the second leading cause of cancer death in men. Despite the frequency of the disease, controversies in management continue for all stages. For patients with localized tumors, deciding whether any treatment is indicated and, if so, selecting the appropriate modalities for an individual patient are at issue. For more advanced local tumors, although definitive data showing a survival benefit are lacking, several groups have been using androgen deprivation prior to surgery or radiation therapy in the hopes of improving local control rates. For patients with established metastases, the timing of androgen ablation is still debated, as is the optimal way to integrate treatments aimed at the androgen-independent cell population--the ultimate cause of death from prostatic cancer. In addition, several groups are focusing on methods to try to predict the natural history of the disease in an individual patient, while reserving the final recommendation on treatment based on the biologic behavior in that individual. PMID- 8494916 TI - Urologic cancer in elderly patients. AB - Although approximately half of the patients with newly diagnosed prostate or bladder cancer are older than the age of 70 years at the time of diagnosis, the literature dealing with the specific problems in this group of patients is limited. More than age alone, existing comorbidity and the patient's preference determine whether radical (curative) treatment is to be applied or whether the therapeutic aims mainly have to be palliative (relief and prophylaxis of distressing symptoms). Small-field radiotherapy, even given at high doses, seems to be an appropriate alternative to radical surgery in many elderly patients, whereas intensive chemotherapy appears less well tolerated in the majority of patients. Only very few reports have dealt with the specific problems in elderly patients with renal cell carcinoma or testicular cancer. In general, more efforts should be undertaken to increase our understanding of the epidemiologic, preventive, and therapeutic problems in elderly patients with urologic cancer. PMID- 8494917 TI - Advances in bladder cancer. AB - Intravesical chemotherapy and immunotherapy are administered to patients with bladder cancer in the hope of decreasing the rate of recurrence and, more importantly, reducing the rate of progression. So far, bacille Calmette-Guerin is the only agent to decrease progression rate and thus increase survival. Bacille Calmette-Guerin has been shown to achieve this outcome by selectively sparing certain sequences during fibronectin degradation; these critical fragments were shown to have motility-stimulating activity, which may then enhance tumor invasion. In vivo and in vitro studies have shown that cathepsin B inhibitors prevent degradation of human basement membrane laminin, which is the first step of tumor invasion. Cathepsin B inhibitors either alone or in combination with bacille Calmette-Guerin may be valuable in preventing the progression of superficial bladder tumors in the future. Clinical studies on bacille Calmette Guerin have repeatedly shown that a second course of bacille Calmette-Guerin to patients with local failure did not jeopardize patient survival. Adjuvant chemotherapy for patients with locally advanced disease and for those with regionally involved lymph nodes improves progression-free survival. Further controlled studies will establish the verdict for adjuvant chemotherapy. With the advancement of molecular genetic studies relevant to modern technology, our understanding of tumor behavior improves dramatically, and classic knowledge becomes more outdated every day. PMID- 8494918 TI - Brain and nervous system. PMID- 8494919 TI - Head and neck cancer. PMID- 8494920 TI - Genitourinary system. PMID- 8494921 TI - Compassionate exemptions. PMID- 8494922 TI - Germ-line gene therapy: another view. PMID- 8494923 TI - Targeting of retroviral vectors for gene therapy. AB - Retroviral vectors are one of the most promising vehicles for the delivery of therapeutic genes in human gene therapy protocols. Retroviral-mediated gene transfer currently being used in human clinical trials is based upon ex vivo transduction of target cells. The ability to target the delivery and expression of therapeutic genes in vivo using retroviral vectors is a prerequisite for widespread and routine use in the clinic and will be of great importance for the safe and successful treatment of certain genetic disorders as well as tumors and viral infections. A number of approaches have been taken to develop retroviral vectors that are able to target particular cell types both at the level of the transduction event and at the level of expression. Using various combinations of the restrictive features reviewed in this article, it should be possible to achieve definitive targeting of genes transduced by retroviral vectors. PMID- 8494924 TI - Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. AB - Striated muscle is the only tissue found to be capable of taking up and expressing reporter genes that are transferred in the form of plasmid DNA. Thus, direct gene transfer is a potential method of gene therapy for the primary inherited myopathies. However, results to date have had insufficient and too variable expression to consider using direct gene transfer in human trials. We have determined that much of the variability of expression is due to nonuniform distribution of substances injected into skeletal muscle in vivo, and have developed a model to ameliorate this. Preinjection of muscles with a relatively large volume of hypertonic sucrose improves the distribution of injected substances and results in significantly less variable expression of reporter genes for luciferase or beta-galactosidase; the coefficient of variation for mean luciferase activity was reduced from about 120% to 25%. Expression is not directly proportional to dose, but is more so if the muscles are preinjected with sucrose than not. Expression is higher and less variable if DNA is injected in a larger than a smaller volume. The choice of promoter appears to be particularly important. Luciferase reporter gene expression from the SV40 promoter was transient and low, whereas expression driven by the Rous sarcoma virus (RSV) promoter was high and sustained, such that a 1,000-fold difference in expression could be observed. The mechanism of gene uptake is still unknown, but our findings indicate that fibers damaged by the injection procedure do not take up and express plasmid DNA. PMID- 8494925 TI - High-efficiency gene transfer to primary monkey airway epithelial cells with retrovirus vectors using the gibbon ape leukemia virus receptor. AB - The efficiency of retrovirus-mediated gene transfer to primary airway epithelial cells from rhesus monkeys was evaluated. We compared the use of murine amphotropic retrovirus vectors to the use of murine retrovirus vectors containing the envelope (Env) glycoproteins from gibbon ape leukemia virus (GALV). These vectors use distinct receptors to gain entry into host cells. We found that vectors with the GALV Env glycoproteins are up to 10-fold more efficient at transducing genes into primary monkey airway epithelial cells than vectors with the amphotropic Env glycoproteins. Under optimal conditions, up to about 80% of primary monkey airway epithelial cells could be transduced with the vector containing the GALV Env glycoproteins. In addition, we found that delivery of retrovirus vectors to the apical side of polarized airway epithelial cultures was significantly more efficient than delivery to the basal side. These results suggest the feasibility of luminal delivery of retrovirus vectors to the lung. PMID- 8494926 TI - Retrovirus-mediated gene transfer into canine thyroid using an ex vivo strategy. AB - We describe studies in a canine model aimed at establishing methods for ex vivo gene delivery to thyroid follicular cells. Canine follicular cells were harvested from tissue obtained by unilateral lobectomy, grown in thyrotropin-containing media, and transduced with amphotropic retroviral vectors carrying Escherichia coli beta-galactosidase or Tn7 neomycin-resistance genes. Up to 30% of cells were transduced with retroviral vectors containing the neomycin resistance gene, and transduced cells could be selected with G418. Significantly, transduced and selected cells exhibited the morphology of thyroid follicular cells and continued to express thyroglobulin. To assess the viability of cultivated and transduced cells for transplantation, cells were stained with the vital fluorescent dye DiI, recovered by trypsinization, and transplanted into the contralateral thyroid lobe of autologous animals. Engraftment was demonstrated by fluorescence microscopy and identification of proviral sequences 7-10 days after transplantation. Proviral transcripts were evident using coupled reverse transcription and the polymerase chain reaction using total RNA from transplanted glands. Thyroid follicular cells may represent an attractive target for gene therapy due to their proliferative potential, their large protein synthetic and secretory capacity, and their susceptibility to regulation. The thyroid might be a target for therapy of congenital or acquired thyroid diseases as well as disorders requiring regulated expression of proteins in the circulation. This work demonstrates the feasibility of ex vivo gene delivery to thyroid follicular cells that may be used in future investigations. PMID- 8494927 TI - Toward gene therapy for hemophilia A: long-term persistence of factor VIII secreting fibroblasts after transplantation into immunodeficient mice. AB - Hemophilia A is caused by the lack of functional blood-clotting factor VIII. We have used retrovirus-mediated gene transfer to generate various cell lines, rodent as well as human, that secrete the human factor VIII protein. To study whether transplantation of genetically modified fibroblasts is a feasible approach for gene therapy of hemophilia A, we implanted the factor VIII-secreting cells into immune-deficient mice. Implantation of factor VIII-secreting primary human skin fibroblasts resulted in long-term persistence of the transplanted cells; cells recovered from the implants up to 2 months post-implantation still had the capacity to secrete factor VIII when regrown in tissue culture. However, we were unable to detect any human factor VIII in plasma samples of the recipient mice. The absence of human factor VIII in the recipients' plasma is shown to be due neither to (epigenetic) inactivation of the retroviral vector in vivo, nor to inability of the stationary cells to secrete factor VIII protein. However, we did note a rapid clearing of the human factor VIII: CAg from plasma upon intravenous injection of plasma-derived human factor VIII in mice (t1/2 < 60 min vs. 10 hr in humans). This phenomenon can fully explain the apparent absence of human factor VIII in the recipients' plasma. PMID- 8494928 TI - Human gene therapy: a biopolitical overview and analysis. AB - The benefits, risks, and social consequences arising from human gene therapy have received substantial citation in the literatures of medical, biological, ethical, and legal commentary. I argue that the question of what "public policy garb" best fits the parameters of human gene therapy in the United States and around the world is a quintessential political question, best understood under the microscope of political science analytic inquiry. I describe the nature of that inquiry, apply its insights to the various ends and means of human gene therapy, and posit empirical models of "political success" for the salient purposes of the craft. I focus particularly on the tract record of the National Institutes of Health's Recombinant DNA Advisory Committee (RAC) in orchestrating the process by which human gene therapy protocols achieve official sanction. PMID- 8494929 TI - Remarks for the RAC Committee meeting of January 14, 1993, regarding compassionate use exemption. PMID- 8494930 TI - "Single patient use" and "emergency use" situations in drug review by the Food & Drug Administration. PMID- 8494931 TI - The effect of peritoneal dialysis fluid on the release of IL-1 beta and TNF alpha by macrophages/monocytes. AB - OBJECTIVE: To study the effect of dialysis fluid on the release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect. DESIGN: PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition. IL-1 beta was measured by radioimmunoassay and TNF alpha by cytotoxicity assay. PATIENTS: PM were obtained by centrifugation of dialysis effluent from 3 continuous ambulatory peritoneal dialysis (CAPD) patients. MNC were obtained from healthy volunteers. RESULTS: Dialysis fluid inhibited the release of both cytokines. Indomethacin had no effect on the inhibition of TNF alpha release caused by dialysis fluid. Thus prostaglandins are not involved in this inhibition. Solutions of pH 5.2 and high lactate concentration caused an identical inhibition to that caused by dialysate, whereas the presence or absence of glucose had no effect. Thus it seems that pH and lactate are the important inhibitory factors. Time course studies showed that the inhibition of TNF alpha release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1 beta became significant only after 60 minutes of incubation. CONCLUSIONS: Even though dialysate pH rises within 15-30 minutes after instillation into the abdomen, the initial low pH present for only a short time could have a significant effect on TNF alpha release by peritoneal macrophages, and thus on their ability to mount a normal inflammatory response. Lactate also has a significant inhibitory role. It is suggested that commercial dialysis solutions should have a pH of 7.0 and that a physiological buffer other than lactate be used. PMID- 8494932 TI - Effects of subcutaneous calcitriol administration on plasma calcium and parathyroid hormone concentrations in continuous ambulatory peritoneal dialysis uremic patients. AB - OBJECTIVE: To ascertain whether the parathyroid hormone (PTH) secretion of continuous ambulatory peritoneal dialysis (CAPD) uremic patients could be suppressed by repeated subcutaneous injections of calcitriol (CLT). DESIGN: Nonrandomized prospective study with weekly evaluation. SETTING: Hospital CAPD clinic. PATIENTS: Seven uremic CAPD patients with signs of severe hyperparathyroidism. INTERVENTIONS: Patients were treated with CLT (2 micrograms), injected subcutaneously three times a week, on alternate days over a period of 8 weeks. MEASUREMENTS: Plasma PTH, ionized calcium (Ca), serum phosphate (Pi), and alkaline phosphatase (AP) were assayed before the start of CLT therapy and weekly thereafter. RESULTS: The average basal PTH was 349 +/- 26 pg/mL (mean +/- SD). It fell significantly by the fifth week to 158 +/- 20, then leveled off. Analysis of the individual data, however, revealed that only 5 of 7 patients had a significant decrease in plasma PTH. Basal Ca was +/- .02 mmol/L; it increased continuously throughout the study, significantly by the fourth week, reaching a level of 1.33 +/- 0.3 mmol/L at the sixth week, then declined slightly. In those patients with significantly decreased PTH, there was an inverse correlation between PTH and the corresponding Ca levels. CONCLUSIONS: In some CAPD patients subcutaneous administration of CLT significantly suppresses PTH. This effect is mainly mediated via an increase in ionized calcium, but a direct inhibitory effect of the vitamin on parathyroid glands cannot be excluded. PMID- 8494933 TI - The pharmacokinetics of a single dose of calcitriol administered subcutaneously in continuous ambulatory peritoneal dialysis patients. AB - OBJECTIVES: To evaluate the kinetics of calcitriol (1,25(OH)2D3) administered subcutaneously. STUDY DESIGN: Calcitriol kinetics and efficacy after subcutaneous administration were studied in 13 CAPD patients with varying degrees of increased plasma levels of parathyroid hormone (i-PTH). A single dose of 2 micrograms of calcitriol was administered subcutaneously, and its serum levels at baseline and after 1, 2, 6, 12, and 24 hours were determined. Plasma ionized calcium and i-PTH were also determined at these periods. RESULTS: Serum calcitriol levels reached peak levels of 60 and 70 pg/mL at 1 and 2 hours after administration, respectively. These levels decreased thereafter, but remained above baseline values during 24 hours. The mean value of the area under the curve (AUC) was 809 +/- 226 pg/mL/hour. Plasma i-PTH levels showed a slight decrease after 1 and 2 hours, returning to baseline levels after this period. Plasma ionized calcium did not show significant changes during the study. A slight pain at the site of injection was mentioned by some patients. CONCLUSIONS: The subcutaneous route for calcitriol administration achieves theoretically adequate plasma levels in continuous ambulatory peritoneal dialysis (CAPD) patients. This is important when parenteral administration of calcitriol is considered in the treatment of secondary hyperparathyroidism. PMID- 8494934 TI - A retrospective assessment of risk factors for peritonitis among an urban CAPD population. AB - Peritonitis is a major reason why patients transfer from peritoneal dialysis (PD) to hemodialysis. We evaluated the peritonitis infection rates in 146 peritoneal dialysis patients who underwent dialysis at our facility between 1 January 1981 and 31 December 1989. Peritonitis was the primary cause for changing treatment, with 24 (16.4%) of the patients transferring because of this complication. This represented 54.5% of all patients discontinuing CAPD due to method failure. A gamma-Poisson regression analysis was performed in an attempt to identify potential risk factors associated with an increased incidence of peritonitis. The results indicated that race, education level, and PD system used were significantly associated with the rate at which peritonitis occurred in our patient population. There was an almost twofold increase in the rate of peritonitis among blacks as compared to whites (2.2 vs 1.2 episodes/patient year). The level of education completed at the start of dialysis had a negative correlation with peritonitis rates. Patients with < or = 8, 9-12, and > or = 13 years of education had peritonitis rates of 2.4, 1.8, and 1.2 episodes/patient year, respectively. Finally, the system used had a significant effect with our patients on CCPD having lower peritonitis rates as compared to patients on either a connect or disconnect system (0.6 vs 2.5 vs 1.8 episodes/patient year, respectively). Recognizing potential risk factors for peritonitis will help us better understand and address this significant problem in our PD programs. Reducing peritonitis rates should facilitate a decrease in patient transfer due to method failure. PMID- 8494935 TI - Initial hypoalbuminemia and hyperlipidemia persist during chronic peritoneal dialysis in children. AB - OBJECTIVE: To document serum lipid values in pediatric peritoneal dialysis (PD) patients, particularly the very young, and investigate relationships with serum albumin levels. DESIGN: Retrospective review of all PD patients seen in the first 11 years of the PD program at our institution. PATIENTS AND METHODS: Any pediatric PD patient was eligible for inclusion if at least four simultaneous measurements of serum lipids and albumin were recorded over a minimum of 90 days of PD. RESULTS: Thirty-nine continuous ambulatory peritoneal dialysis (CAPD) patients (9, aged < 5 years) and 14 continuous cycling peritoneal dialysis (CCPD) patients (7, aged < 5 years) were followed for 90-1200 days. Hypoalbuminemia, present in 43% of initial recordings, did not alter significantly during PD in any group; it was most marked in the CAPD < 5 year (mean 30.7 g/L) and CCPD > 5 year groups (mean 31.4 g/L). Average serum cholesterol levels were 27% higher, and triglyceride 122% higher, than the maximum accepted 18-year-old level and did not change significantly during PD. Similarly, 33% of high-density lipid recordings were below normal and remained unaltered during PD. CONCLUSIONS: Our results confirm the high incidence of hypoalbuminemia, hypertriglyceridemia, and hypercholesterolemia and associated low levels of high-density lipids, even in young PD patients, and demonstrate that these remain unchanged during PD. Such results have not previously been reported in PD patients as young as ours. Abnormal lipid profiles are a neglected cardiovascular risk factor in children with renal failure; therapeutic interventions should therefore be seriously considered. PMID- 8494936 TI - CAPD therapy for patients over 80 years of age. AB - OBJECTIVE: The purpose of the study is to review our experience with patients over 80 years of age with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: The records of all patients over 80 years of age treated in our unit with CAPD since 1979 were reviewed. SETTING: Out-patient CAPD facility. PATIENTS: Eighteen patients over 80 years of age were identified and studied. MAIN OUTCOME MEASURES: The duration of CAPD therapy, duration of CAPD training, mortality rate, hospitalization rate, peritonitis rate, and family assessment were reviewed and analyzed. RESULTS: The mean +/- SD duration of therapy was 20 +/- 17 months. Nine patients expired, 3 transferred to hemodialysis, 1 recovered renal function, and 5 remained on CAPD therapy. Peritonitis rates were 1.7 episodes/patient year. Of the organisms causing peritonitis, 56% were gram-positive bacteria. The average hospitalization rate was 13.9 days/patient year. The most frequent causes of hospitalization were peritonitis and cardiovascular disease. CONCLUSION: CAPD therapy is a reasonable therapeutic option for patients with end-stage renal disease over 80 years of age. PMID- 8494937 TI - Peritoneal dialysis catheter exit-site care: results of an international survey. AB - A survey was developed to determine the prevalence of specific components of postoperative and chronic peritoneal catheter exit-site care procedures. Surveys were mailed to approximately 1800 participants of the 1991 Peritoneal Dialysis Conference; 585 surveys (80.6% from the United States and 96% from adult units) were analyzed. The most frequent components of postoperative exit-site care were the use of prophylactic antibiotics, daily dressing changes, procedures limited to specially trained staff, use of sterile technique, povidone iodine and hydrogen peroxide as cleansing agents, and gauze dressings. The most frequent components of chronic exit-site care procedures were daily care done with shower or bathing, antibacterial or pure soap for cleansing, hydrogen peroxide only as needed, catheter stabilization, dressings optional, and gauze dressings when used. Twice daily exit care, change in cleansing agent, and topical antibiotics were recommended for inflamed or infected exit sites. There were significant differences between the United States and other locations, particularly in the type of cleansing agent, use of hydrogen peroxide, and use of dressings for chronic care. Pediatric programs (all located in the United States or Canada) differed somewhat from adult programs in North America. Pediatric patients and their families were significantly more likely to be trained to do postoperative dressing changes and significantly less likely to perform exit-site care at the time of showering or bathing. PMID- 8494938 TI - Supplementing renal function with CAPD in a patient with chronic renal failure and pregnancy. PMID- 8494939 TI - Percutaneous embolization of splenic artery pseudoaneurysm as a treatment of hemoperitoneum in a CAPD patient. PMID- 8494940 TI - Intraperitoneal albumin infusion and pain. PMID- 8494941 TI - Chemical peritonitis after intraperitoneal administration of amphotericin B in a fungal infection of the catheter subcutaneous tunnel. PMID- 8494942 TI - Fungal peritonitis with splenic-pelvic abscess in a patient on continuous ambulatory peritoneal dialysis. PMID- 8494943 TI - Recurrent Salmonella peritonitis in a patient on CAPD. PMID- 8494944 TI - Salmonella enteritidis causing CAPD peritonitis. PMID- 8494945 TI - The influence of dialysate volume on the peritoneal equilibration test. PMID- 8494946 TI - Literature. April-May 1993. PMID- 8494947 TI - Biocompatibility of peritoneal dialysis solutions. PMID- 8494948 TI - Calcitriol and secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis patients. PMID- 8494949 TI - In search of a role for submesothelial fenestrated capillaries. PMID- 8494950 TI - Porcelain color plates for immunohistochemical incubation of free-floating tissue sections. AB - Porcelain color plates are a convenient alternative to multiwell plastic plates for immunohistochemical incubations. The advantage of the plates are that they allow relatively large tissue sections to float freely in small volumes of liquid and allow easy access to the sections. PMID- 8494952 TI - A simple and safe device for spreading ultrathin sections with chloroform. AB - A simple and safe device for spreading ultrathin sections for electron microscopy is described. The use of this device minimizes the release of chloroform vapor during section spreading. PMID- 8494951 TI - An improved method for studying microvascular geometry using fluorescent dyes: preventing dye extravasation, preserving dye integrity and enhancing tissue morphometry. AB - A procedure for stabilizing fluorescent markers used to study the microvascular geometry and morphometry of muscle tissue is described. The procedure involves fluorescent labeling of plasma, fixation of muscle tissue in 10% buffered formalin, and quick freezing. This procedure prevents extravasation of the fluorescent dyes out of the capillaries as frequently seen in other muscle microvascular techniques, thereby greatly increasing the time that capillaries are visible. We found that formalin may actually increase the rate of fluorochrome bleaching by photo-oxidation, but the increased rate of bleaching is more than offset by the greater concentration of dye trapped in the capillaries. Further, formalin fixation results in little distortion of the muscle fibers themselves, making this approach ideal for morphometric studies. PMID- 8494953 TI - Microwave irradiation for rapid and enhanced immunohistochemical staining: application to skin antigens. AB - We describe a method in which microwave irradiation is used to reduce substantially the incubation time for immunoperoxidase staining of antigens in cryostat sections of psoriatic skin. An incubation time of 5-9 min irradiation at 80 W generated similar or better staining intensity for all antibodies used compared to the standard methods using 30-60 min incubation at room temperature. Although we found that microwave irradiation could be used with all antibodies tested, independent of whether they recognized extracellular, membrane or cytoplasmic antigens in skin, the conditions needed to be optimized for each antibody. PMID- 8494954 TI - Fixation for the 1990's: a review of needs and accomplishments. AB - Neutral buffered formalin (NBF) has been the standard fixative in histopathology for many decades; however, new technologies and increasing time constraints have made this common fixative less widely applicable. The attributes of universal and ideal fixatives are reviewed and compared with those of NBF. On the strength of a growing body of literature and experience in the histopathology field, zinc formalin solutions are recommended as a functional replacement for NBF. Zinc formalin permits better morphological preservation and preserves immunoreactivity even after prolonged fixation times. Coordinated zinc ions are postulated to maintain macromolecules in their original three-dimensional conformation as formaldehyde forms addition products with them. Significant crosslinking and gross distortion of tertiary structure are thereby avoided. PMID- 8494955 TI - Giemsa G-banding in Allium. AB - Using divergent Giemsa staining protocols designed for other plant species, G banding was visualized in the chromosomes of Allium cepa L., A. fistulosum L., and their interspecific (A. fistulosum x A. cepa) hybrid. This is the first demonstration of G-banding of Allium chromosomes. Differences and similarities with other Giemsa banding patterns in Allium are discussed. PMID- 8494956 TI - [The definition of excessive alcohol consumption and its implications]. PMID- 8494957 TI - [Psychopharmaceuticals in primary care: prescription quality]. AB - OBJECTIVE: Using criteria based on the bibliography, to assess drugs prescription in a Health Centre, in order to put forward corrective measures in line with the defects identified. DESIGN: Descriptive and retrospective study. SETTING: Santa Maria de Benquerancia Health Centre (Toledo). PARTICIPANTS: A sample of 40% of the clinical records of patients over 14 produced records of patients treated with drugs for psychic disorders between October 1990 and October 1991. MEASUREMENTS AND MAIN RESULTS: 248 prescriptions for these drugs were found. The most common diagnoses were: neurotic depression (33.1%), anxiety (25.8%) and insomnia (10.1%). Benzodiazepines made up 78.2% of the prescriptions. Of 8 quality criteria assessed, the compliance level was acceptable by WHO standards except in the recording in the notes of the diagnosis or problem for which the drug was prescribed (74.2% non-compliance); Alprazolam and Triazolam were not considered first-choice benzodiazepines (31.3% non-compliance); and there was 44.5% non-compliance by Primary Care physicians with the non-prescription of anti psychotic or stimulant MAO inhibitor antidepressants. CONCLUSIONS: Quality control studies, such as this one, in order to identify problems, to take corrective measures and subsequently assess them, are useful in improving care procedures. PMID- 8494958 TI - [The vaccination coverage in a cohort of children at 2 years of age from a health area]. AB - OBJECTIVES: To estimate the vaccination coverage of two-years-old children in the health district of Gijon (Spain), the number of incomplete vaccinations and their causes. To evaluate the vaccination registry coverage. DESIGN: Descriptive cross sectional survey. SITE. Primary health care. PATIENTS: From the cohort born in 1989, living in the health district, a sample of 219 children was taken. Of these, criteria for inclusion in the study were met by 199 (90.8%), and the vaccination status was ascertained in 191 (87.2%). MAIN MEASUREMENTS AND RESULTS: The variables related with the vaccination coverage were studied through registrations or specific questionnaires. The full vaccination coverage with 3 doses of DTP, 1 dose of DT, 4 doses of VPO and one dose of MMR in the district was 92.5%. Estimating vaccination coverage using only our public registration systems, would lower it to 84.9. This result suggest that the public sector vaccination registry in Gijon under-registers immunizations. Vaccination coverage was 99.5% for first dose (3 months: DTP and VPO) and 93.5% for last doses (18 months: DT and VPO). For MMR it was 94.5%. CONCLUSIONS: Our data suggests there is a high vaccination coverage in the Gijon area. We consider population's questionnaires a satisfactory way to estimate vaccination coverage, and besides to evaluate the validity of the usual registers to use them as information resource. PMID- 8494959 TI - [The detection of alcoholism in a general population by using the Cage test]. AB - OBJECTIVE: To identify people with alcohol-related problems and assess the variable socio-demographic indicators of the population under study. DESIGN: Crossover and observational study. SETTING: The "Occidente" Basic Health Area in Cordoba. PARTICIPANTS: A representative sample of those people over 15 registered in the Health Area mentioned above. (Systematic random sampling: n = 384). MEASUREMENTS AND MAIN RESULTS: 72% of those interviewed stated that they had consumed some kind of alcoholic drink during the previous year. 35% did so at least once a week. 6.2% +/- 2.35 showed positive on the CAGE Test, most of these being: male (p < 0.001), living in a deprived area (p < 0.01), people in work (p < 0.001) and smokers (p < 0.001). Those testing CAGE (+) included a higher number of people with: hepatitis, cirrhosis, diarrhea and gastritis, although their use of health services was no different from that of the population as a whole. Logistic regression analysis enabled us to establish variable indicators of the CAGE Test (+). CONCLUSIONS: Alcohol-related problems were identified basically in a typical population group. It is important to set up intervention mechanisms to tackle the problem. PMID- 8494960 TI - [An analysis of the responses to the Cage test obtained among young people from a rural area]. AB - OBJECTIVE: The aim of this study is to detect alcoholism problems among the young population, using the CAGE test. DESIGN: Transversal descriptive study. SITE. Work developed with high school students (BUP and COU) from a rural context in Aragon. PATIENTS AND OTHER PARTICIPANTS: Random sample of 1,012 students, ordered by gender and academic course (57.9% female, age average 16 +/- 1.3 years old). INTERVENTIONS: The CAGE test was answered in written and anonymous way. MAIN MEASUREMENTS AND RESULTS: 368 students (36.5%) obtained scores. 1. Among them, 159 (15.7%) scored 2. The prevalence of alcoholism was greater in male students (p = 0.01). The test shows false positivity in 7 sober people. Youngsters with high scores presented higher risk of suffering a traffic accident (p = 0.001). CONCLUSIONS: Because of the psychological peculiarities of the teenagers CAGE test might have some reliability disturbances. In any case, the results show the existence of an important number of young people in the rural site with problems related to alcohol (although not necessarily linked to physical dependence. PMID- 8494961 TI - [An evaluation of the quality of the medical information passing between primary care and specialist levels]. AB - OBJECTIVE: To study the quality of the information exchanged in internal notes between Primary Care and specialist doctors and to determine which features of both the professionals and the system of organisation are common to both. DESIGN: Observational study of a crossover type in which the units under analysis were the inter-clinic notes exchanged. SETTING: Information gathering was carried out by means of personal attendance at specialist out-patient clinics in Area V, Madrid. MATERIALS: A sampling of 1,920 inter-clinic notes accompanying patients referred by 45 general physicians to 13 Specialist Care clinics, including both ordinary clinics and senior specialists. MEASUREMENTS AND MAIN RESULTS: Criteria concerning the quality of documentation exchanged were defined both according to the clinical information contained and the legibility of the inter-clinic notes. The quality of information sent by the general physician was good in 45% of cases. The highest quality of information in the inter-clinic notes sent by the general physicians was linked to Primary Care team-work, MIR training and women doctors. CONCLUSIONS: The information accompanying patients referred from Primary Care to specialists is low-quality. Doctors working in Primary Care Teams produce higher quality inter-clinical notes. PMID- 8494962 TI - [An epidemiological study on the alcohol consumption habits in an urban population]. AB - OBJECTIVE: To quantify alcohol consumption in the town of Valls, differentiating working days from the week-ends, and to find the prevalence of excessive drinkers. DESIGN: Crossover observational study, with a population base. SETTING: Family and community medicine teaching centre of the Primary Care Clinic in Valls, a town with 20,004 inhabitants in the province of Tarragona. PARTICIPANTS: A random sample stratified by sex and age according to the municipal pattern (N = 327 people between 15 and 90). A home interview by the investigator, including a 24-hour record of alcohol consumption (discriminating between working days and the week-end). MEASUREMENTS AND MAIN RESULTS: Males consumed an average of 23 gr of alcohol per working day and 42.9 gr of alcohol per week-end day (86.5% increase). Women consumed an average of 5.1 gr of alcohol per working day and 18.1 gr per week-end day (255% increase). The proportion of excessive drinkers (more than 60 gr per day in men and 40 gr per day in women) was 12.4% of men and 4.8% of women on working days; and 32.3% of men and 19.9% of women on week-end days. Consumption was significantly related to gender and age groups. CONCLUSIONS: A notable increase in alcohol consumption at the weekend was noted. This is occurring most of all at the expense of the young, who apparently now regularly consume alcohol according to an Anglo-Saxon type pattern. PMID- 8494963 TI - [The evaluation of a semiautomatic arterial pressure monitor]. AB - OBJECTIVE: To study the reliability and precision of the arterial pressure digital monitor, Palm Monitor-2 FS-40, model 1083 (DM). The mercury sphygmomanometer (MSM) was used as the reference. DESIGN: Comparative crossover study. SETTING: Primary Care Centre. PATIENTS: 81 patients of both sexes between 26 and 65 found at random in a consultation during November and December, 1991. 24 of them had systolic arterial pressure (SAP) above 140 mmHg and/or diastolic arterial pressure (DAP) above 90 mmHg. MEASUREMENTS AND MAIN RESULTS: Four measurements of AP for each patient were carried out at one minute intervals: the first and the fourth with the MSM and the second and third with the DM. The SAP averages with the DM were 130.27 mmHg in the first take and 129.36 in the second. The DAP averages were 82.53 and 81.88, respectively. The Pearson correlation r between the averages for both devices and the difference of averages, both absolute and in so much per cent, were obtained. The values obtained were 0.887 for SAP and 0.810 for DAP. The difference between averages was -3.83 mmHg ( 2.86%) for SAP and -2.55 mmHg (-3.04%) for DAP. CONCLUSIONS: The measurements obtained with this DM are quite reliable, although a tendency to underestimate the AP values in relation to the MSM was noted. Overall it can provide useful information on certain aspects of the diagnosis and follow-up of AHT. PMID- 8494964 TI - [An evaluation of the infant program at a health center]. AB - OBJECTIVE: Infant programme evaluation in our health centre. DESIGN: Descriptive study, with random sample. SITE. Torrero-La Paz Health Centre in Zaragoza. PATIENTS AND OTHER PARTICIPANTS: Fifty medical records of all the 275 infants younger than two years old included in the "Infant Programme". MAIN MEASUREMENTS AND RESULTS: Some criteria were studied with its standards previously accented by the team. The obtained results were compared with the standards. The programme coverage was 70%, with 10% of loss. There were some criteria that indicated a good accomplishment of the programme, such as vaccination (87.2%), Hischberg test (87%), testicle examination (96.5%, preventive fluorine administration (92.5%). Others got lower results: dry spot screening (76%), maternal lactation advise (70%), maternal/mixed lactation at the third month (36%). The pathology detected in programmed check-ups was principally urologic disorders. CONCLUSIONS: Poor structure for the programme performance in despite of the fact there is a good follow-up of the programme activities. It would be necessary to insist on the maternal lactation advise and lactation at the third month. PMID- 8494965 TI - [Recent capsular-ligamentous lesions of the knee and primary care]. PMID- 8494966 TI - [EDTA-induced pseudothrombocytopenia in primary care]. PMID- 8494967 TI - [Pasteurella multocida infection after a cat bite]. PMID- 8494968 TI - [Are we attending properly to the needs of our terminal cancer patients?]. PMID- 8494969 TI - [Acute asthenia]. PMID- 8494970 TI - Lateral diffusion in an archipelago. Dependence on tracer size. AB - In a pure fluid-phase lipid, the dependence of the lateral diffusion coefficient on the size of the diffusing particle may be obtained from the Saffman-Delbruck equation or the free-volume model. When diffusion is obstructed by immobile proteins or domains of gel-phase lipids, the obstacles yield an additional contribution to the size dependence. Here this contribution is examined using Monte Carlo calculations. For random point and hexagonal obstacles, the diffusion coefficient depends strongly on the size of the diffusing particle, but for fractal obstacles--cluster-cluster aggregates and multicenter diffusion-limited aggregates--the diffusion coefficient is independent of the size of the diffusing particle. The reason is that fractals have no characteristic length scale, so a tracer sees on average the same obstructions, regardless of its size. The fractal geometry of the excluded area for tracers of various sizes is examined. Percolation thresholds are evaluated for a variety of obstacles to determine how the threshold depends on tracer size and to compare the thresholds for compact and extended obstacles. PMID- 8494971 TI - Orientational behavior of phosphatidylcholine bilayers in the presence of aromatic amphiphiles and a magnetic field. AB - A number of aromatic-containing additives which can influence the orientation of fragments of lipid bilayer membranes by a magnetic field have been investigated. Two properties of these additives prove important: (1) sufficient detergency to facilitate reorganization of bilayer components and (2), sufficient anisotropy in magnetic susceptibility the preferred direction of fragment orientation. Triton X 100 is identified as effective in terms of facilitating magnetic field ordering of bilayer fragments but does not alter the preferred direction of orientation. A combination of the detergent CHAPSO (3-[(3-cholamidopropyl)-dimethylammonio]-1 propane sulfonate) and the aromatic alcohol 1-naphthol facilitates both ordering and alters the preferred direction of bilayer orientation. As mixtures of dimyristoylphosphatidylcholine (DMPC) and CHAPSO, which orient with bilayer normals perpendicular to the magnetic field, were titrated with 1-naphthol, the assemblies underwent transitions, first to random orientation, and then to an orientation with bilayer normals parallel to the field. Based on temperature induced phase transitions and the extent of motional averaging of the 31P shielding tensor of the DMPC headgroup, the DMPC in these oriented samples appears to maintain a bilayer morphology during transitions. The insight provided in this study regarding factors which influence fragment stability and orientation lays the groundwork for the design of improved field-oriented media for spectroscopic investigation of membrane components. PMID- 8494972 TI - Calorimetric and spectroscopic studies of the polymorphic phase behavior of a homologous series of n-saturated 1,2-diacyl phosphatidylethanolamines. AB - The polymorphic phase behavior of a homologous series of n-saturated 1,2-diacyl phosphatidylethanolamines was investigated by differential scanning calorimetry, 31P-nuclear magnetic resonance, and Fourier transform infrared spectroscopy. Upon heating, aqueous dispersions of dried samples of the short- and medium-chain homologues (n < or = 17) exhibit single, highly energetic transitions from a dry, crystalline form to the fully hydrated, liquid-crystalline bilayer at temperatures higher than the lamellar gel-liquid-crystalline phase transition exhibited by fully hydrated samples. In contrast, the longer chain homologues (n > or = 18) first exhibit a transition from a dehydrated solid form to the hydrated L beta gel phase followed by the gel-liquid-crystalline phase transition normally observed with fully hydrated samples. The fully hydrated, aqueous dispersions of these lipids all exhibit reversible, fairly energetic gel-liquid crystalline transitions at temperatures that are significantly higher than those of the corresponding phosphatidylcholines. In addition, at still higher temperatures, the longer chain members of this series (n > or = 16) exhibit weakly energetic transitions from the lamellar phase to an inverted nonlamellar phase. Upon appropriate incubation at low temperatures, aqueous dispersions of the shorter chain members of this homologous series (n < or = 16) form a highly ordered crystal-like phase that, upon heating, converts directly to the liquid crystalline phase at the same temperature as do the aqueous dispersions of the dried lipid. The spectroscopic data indicate that unlike the n-saturated diacyl phosphatidylcholines, the stable crystal-like phases of this series of phosphatidylethanolamines describe an isostructural series in which the hydrocarbon chains are packed in an orthorhombic subcell and the headgroup and polar/apolar interfacial regions of the bilayer are effectively immobilized and substantially dehydrated. Our results suggest that many of the differences between the properties of these phosphatidylethanolamine bilayers and their phosphatidylcholine counterparts can be rationalized on the basis of stronger intermolecular interactions in the headgroup and interfacial regions of the phosphatidylethanolamine bilayers. These are probably the result of differences in the hydration and hydrogen bonding interactions involving the phosphorylethanolamine headgroup and moieties in the polar/apolar interfacial regions of phosphatidylethanolamine bilayers. PMID- 8494973 TI - Measurement of chain tilt angle in fully hydrated bilayers of gel phase lecithins. AB - The tilt angle theta tilt of the hydrocarbon chains has been determined for fully hydrated gel phase of a series of saturated lecithins. Oriented samples were prepared on glass substrates and hydrated with supersaturated water vapor. Evidence for full hydration was the same intensity pattern of the low angle lamellar peaks and the same lamellar repeat D as unoriented multilamellar vesicles. Tilting the sample permitted observation of all the wide angle arcs necessary to verify the theoretical diffraction pattern corresponding to tilting of the chains towards nearest neighbors. The length of the scattering unit corresponds to two hydrocarbon chains, requiring each bilayer to scatter coherently rather than each monolayer. For DPPC, theta tilt was determined to be 32.0 +/- 0.5 degrees at 19 degrees C, slightly larger than previous direct determinations and considerably smaller than the value required by recent gravimetric measurements. This new value allows more accurate determinations of a variety of structural parameters, such as area per lipid molecule, A = 47.2 +/- 0.5 A2, and number of water molecules of hydration, nw = 11.8 +/- 0.7. As the chain length n of the lipids was increased from 16 to 20 carbons, the parameters A and nw remained constant, suggesting that the headgroup packing is at its excluded volume limit for this range. However, theta tilt increased by 3 degrees and the chain area Ac decreased by 0.5 A2. This behavior is explained in terms of a competition between a bulk free energy term and a finite or end effect term. PMID- 8494974 TI - Evidence of partial rotational order in gel phase DPPC. AB - It is shown how the dichroic ratio of the symmetric methylene stretching modes depends upon both the rotational order of hydrocarbon chains about their long axis and the tilting of the long chains with respect to the bilayer normal. Use of a recent determination of the tilt angle from x-ray measurements together with recent dichroic infrared data yields a rotational order parameter g = -0.30 compared to g = 0 for complete disorder and g = +/- 1 for complete order. The negative value of g corresponds to a preference for the plane defined by the chain carbons to be more perpendicular than parallel to the plane defined by the tilt direction and the bilayer normal. PMID- 8494975 TI - A new infrared spectroscopoic marker for cochleate phases in phosphatidylserine containing model membranes. AB - Fourier transform-infrared (IR) spectroscopic and electron microscopic studies are reported for 1,2-dimyristoylphosphatidylserine (DMPS) and for DMPS/1,2 dimyristoylphosphatidylcholine mixtures in the presence and absence of Ca2+ ion. The frequency of the methyl symmetric deformation mode near 1,378 cm-1, previously assumed insensitive to changes in lipid morphology, has been found to respond to cochleate phase formation by undergoing an approximately 8 cm-1 increase. The new IR spectroscopic marker at 1,386 cm-1 has been used to identify and verify structures suggested from the phase diagram of J. R. Silvius and J. Gagne (1984. Biochemistry. 23:3241-3247) for this system. In addition, the ability of Mg2+ ion to induce cochleate formation has been demonstrated. Higher Mg2+ than Ca2+ levels are required for this process. Finally, IR spectroscopy has been used to monitor dehydration of the lipid surface through changes in the asymmetric PO2- stretching mode. Dehydration precedes cochleate phase formation (i.e., occurs at a lower Ca2+/phosphatidylserine level). PMID- 8494976 TI - Cross-bridge attachment and stiffness during isotonic shortening of intact single muscle fibers. AB - Equatorial x-ray diffraction pattern intensities (I10 and I11), fiber stiffness and sarcomere length were measured in single, intact muscle fibers under isometric conditions and during constant velocity (ramp) shortening. At the velocity of unloaded shortening (Vmax) the I10 change accompanying activation was reduced to 50.8% of its isometric value, I11 reduced to 60.7%. If the roughly linear relation between numbers of attached bridges and equatorial signals in the isometric state also applies during shortening, this would predict 51-61% attachment. Stiffness (measured using 4 kHz sinusoidal length oscillations), another putative measure of bridge attachment, was 30% of its isometric value at Vmax. When small step length changes were applied to the preparation (such as used for construction of T1 curves), no equatorial intensity changes could be detected with our present time resolution (5 ms). Therefore, unlike the isometric situation, stiffness and equatorial signals obtained during ramp shortening are not in agreement. This may be a result of a changed crossbridge spatial orientation during shortening, a different average stiffness per attached crossbridge, or a higher proportion of single headed crossbridges during shortening. PMID- 8494977 TI - Viscoelasticity of the sarcomere matrix of skeletal muscles. The titin-myosin composite filament is a dual-stage molecular spring. AB - The mechanical roles of sarcomere-associated cytoskeletal lattices were investigated by studying the resting tension-sarcomere length curves of mechanically skinned rabbit psoas muscle fibers over a wide range of sarcomere strain. Correlative immunoelectron microscopy of the elastic titin filaments of the endosarcomeric lattice revealed biphasic extensibility behaviors and provided a structural interpretation of the multiphasic tension-length curves. We propose that the reversible change of contour length of the extensible segment of titin between the Z line and the end of thick filaments underlies the exponential rise of resting tension. At and beyond an elastic limit near 3.8 microns, a portion of the anchored titin segment that adheres to thick filaments is released from the distal ends of thick filament. This increase in extensible length of titin results in a net length increase in the unstrained extensible segment, thereby lowering the stiffness of the fiber, lengthening the slack sarcomere length, and shifting the yield point in postyield sarcomeres. Thus, the titin-myosin composite filament behaves as a dual-stage molecular spring, consisting of an elastic connector segment for normal response and a longer latent segment that is recruited at and beyond the elastic limit of the sarcomere. Exosarcomeric intermediate filaments contribute to resting tension only above 4.5 microns. We conclude that the interlinked endo- and exosarcomeric lattices are both viscoelastic force-bearing elements. These distinct cytoskeletal lattices appear to operate over two ranges of sarcomere strains and collectively enable myofibrils to respond viscoelastically over a broad range of sarcomere and fiber lengths. PMID- 8494978 TI - Structural transformation of collagen fibrils in corneal stroma during drying. An x-ray scattering study. AB - X-ray scattering experiments were performed on human corneas during drying. In a first stage the collagen interfibrillar distance decreased considerably. Then, at a critical point of dehydration, a structural transformation of the collagen fibrils was observed. This finding leads to a two-stage drying model, which explains the discrepancy between the collagen fibril diameters determined by x ray scattering and by electron microscopy. Our results strongly suggest that the collagen fibrils in the corneal stroma are surrounded by a cylindrical coating made mainly of proteoglycans. The coating appears as a three-dimensional fractal network with fractal dimension of 2.7 +/- 0.1. PMID- 8494979 TI - Fourier transform infrared spectroscopy characterization of the lamellar and nonlamellar structures of free lipid A and Re lipopolysaccharides from Salmonella minnesota and Escherichia coli. AB - The structural polymorphism of free lipid A and deep rough mutant lipopolysaccharide (LPS Re) from Salmonella minnesota strain R595 and Escherichia coli strain F515 was characterized by Fourier transform infrared (IR) spectroscopy. For this, the beta <--> alpha phase states and the three dimensional supramolecular structures, the latter deduced from small-angle synchrotron radiation x-ray diffraction, were investigated at different water contents, Mg2+ concentrations, and temperatures. The analysis of the IR data for vibrations originating from the hydrophobic moiety shows that the beta <--> alpha acyl chain melting is strongly expressed only for the stretching and scissoring modes of the methylene groups. Vibrational groups originating from the interface region sense the acyl chain melting well (ester carbonyl bands) or only weakly (amide bands), and those resulting from the pure polar moiety not at all. From the x-ray data, the existence of lamellar (L), different cubic, and, for lipid A and LPS R595, also inverted hexagonal (HII) structures could be proven in the temperature range 20-80 degrees C with cubic <--> cubic and cubic <--> HII transitions for the Mg(2+)-free and L <--> HII transitions for the Mg(2+) containing samples. These structural transitions can be characterized most readily by specific changes of the vibrational bands resulting from the interface region: the ester carbonyl and the amide bands. The magnitude of the changes corresponds to that of the structural rearrangement, i.e., is highest for the L < -> HII, lower for the cubic <--> HII, and lowest for the cubic <--> cubic transitions. The structural transitions are only marginally expressed for vibrational bands of the hydrophobic moiety. Similarly, the band contours of vibrations from the hydrophilic region are no indicators of the structural reorientations except for the carboxylate bands of LPS Re. Particularly the stretching vibrations of the phosphate groups are nearly completely invariant; the absolute values of their half bandwidths, however, differ significantly for lipid A and LPS Re, which seems to be of biological relevance. The ability of IR spectroscopy to detect supramolecular changes also beyond the measurability by x ray diffraction, i.e., at water contents > 95 to 99.5%, is demonstrated. PMID- 8494980 TI - Designing matrix models for fluorescence energy transfer between moving donors and acceptors. AB - A recipe is given for designing theoretical models for donor-acceptor systems in which fluorescence energy transfer and motion takes place simultaneously. This recipe is based on the idea that a system exhibiting both motion and fluorescence energy transfer can be modeled by specifying a number of "states" and the rates of transitions between them. A state in this context is a set of specific coordinates and conditions that describe the system at a certain moment in time. As time goes on, the coordinates and conditions for the system change, and this evolution can be described as a series of transitions from one state to the next. The recipe is applied to a number of example systems in which the donors and/or acceptors undergo either rotational or translational motion. In each example, fluorescence intensities and anisotropies for the donor and acceptor are calculated from solutions of eigensystems. The proposed method allows for analyzing time-resolved fluorescence energy transfer data without restrictive assumptions for motional averaging regimes and the orientation factor. It is shown that the fluorescence quantities depend on the size of the motional step (i.e., on the number of states), only if fluorescence energy transfer occurs. This finding indicates that fluorescence energy transfer studies may reveal whether the dynamics of a system (e.g., a protein) is better described in terms of transitions between a relatively small number of discrete states (jumping) or a large number of dense states (diffusion). PMID- 8494981 TI - Thermodynamics of anesthetic/protein interactions. Temperature studies on firefly luciferase. AB - Firefly luciferase is a soluble enzyme which is unusually sensitive to general anesthetics. The inhibition of the highly purified enzyme by three inhalational and three alcohol general anesthetics has been studied as a function of temperature, in the range from 5 to 20 degrees C. Inhibition constants Ki were determined at different temperatures, and van't Hoff plots of ln (Ki) versus reciprocal absolute temperature were found to be linear for all agents. Analysis of these plots gave values for the standard Gibbs free energy, enthalpy and entropy changes for transferring each anesthetic from water to the anesthetic binding pocket on the protein. The most striking finding was that the enthalpy changes were much more negative for anesthetics binding to the protein than for binding to lipids or simple solvents. Furthermore, amongst the set of anesthetics studied, it was found that increasing potency correlated with favorable enthalpy rather than entropy changes. We discuss our results with respect to the molecular mechanisms underlying general anesthesia. PMID- 8494982 TI - An enthalpic model of anesthesia. PMID- 8494983 TI - Sodium interaction with ordered structures in mammalian red blood cells detected by Na-23 double quantum NMR. AB - Na-23 double and triple quantum filtered NMR spectra of intact dog and human red blood cells were measured with the pulse sequence 90 degrees-tau/2-180 degrees tau/2-theta degrees-t1-theta degrees-t2(Acq). For theta = 90 degrees the triple quantum filtered spectra exhibited the typical multiple quantum filtered lineshape, characteristic of isotropic media, while the double quantum filtered ones presented a superposition of two signals, whose proportion depended on the creation time tau. This effect is due to the formation of both second and third rank tensors. The formation of the second rank tensor, T21 results from non-zero residual quadrupolar interaction and is related to the anisotropic motion of sodium ions. Measurements of the double quantum filtered spectra with theta = 54.7 degrees enabled the detection of the contribution of T21 exclusively. No residual quadrupolar interaction was detected for sodium in the cytoplasm, while unsealed ghosts displayed the double quantum filtered spectral pattern, similar to that of intact cells. The anisotropy of motion of the sodium at the plasma membrane of mammalian erythrocytes depended on the integrity of the cytoskeleton network. Theoretical analysis of the double quantum filtered spectra gave a value of residual quadrupolar splitting of approximately 20 Hz for intact unsealed ghosts. The data presented prove that double quantum filtering is a sensitive technique for detection of motional anisotropies in biological systems. PMID- 8494984 TI - Cytoskeleton of living, unstained cells imaged by scanning force microscopy. AB - Subsurface cytoskeletal structure can be visualized in either fixed or living mammalian cells in aqueous medium with approximately 50 nm resolution using the Scanning Force Microscope (SFM). In living cells, changes in cell topography, or subsurface cytoskeleton caused by the introduction of drugs (colchicine) or cross linking of surface receptors (by antibodies against IgE bound to the IgE receptor) can be followed in time. Contrast in SFM images of cell surfaces result from both topographic features of the cell and from variations in cell surface "stiffness". The SFM is therefore capable of measuring local compliance and stress in living cells, and so should make it possible to map the cytoskeletal forces used to generate cell motions and changes in cell shape. PMID- 8494985 TI - The biomagnetic signature of a crushed axon. A comparison of theory and experiment. AB - The response of a crayfish medial giant axon to a nerve crush is examined with a biomagnetic current probe. The experimental data is interpreted with a theoretical model that incorporates both radial and axial ionic transport and membrane kinetics similar to those in the Hodgkin/Huxley model. Our experiments show that the effects of the crush are manifested statically as an elevation of the resting potential and dynamically as a reduction in the amplitude of the action current and potential, and are observable up to 10 mm from the crush. In addition, the normally biphasic action current becomes monophasic near the crush. The model reflects these observations accurately, and based on the experimental data, it predicts that the crush seals with a time constant of 45 s. The injury current density entering the axon through the crush is calculated to be initially on the order of 0.1 mA/mm2 and may last until the crush seals or until the concentration gradients between the intra- and extracellular spaces equilibrate. PMID- 8494986 TI - New physical concepts for cell amoeboid motion. AB - Amoeboid motion of cells is an essential mechanism in the function of many biological organisms (e.g., the regiment of scavenger cells in the immune defense system of animals). This process involves rapid chemical polymerization (with numerous protein constituents) to create a musclelike contractile network that advances the cell over the surface. Significant progress has been made in the biology and biochemistry of motile cells, but the physical dynamics of cell spreading and contraction are not well understood. The reason is that general approaches are formulated from complex mass, momentum, and chemical reaction equations for multiphase-multicomponent flow with the nontrivial difficulty of moving boundaries. However, there are strong clues to the dynamics that allow bold steps to be taken in simplifying the physics of motion. First, amoeboid cells often exhibit exceptional kinematics, i.e., steady advance and retraction of local fixed-shape patterns. Second, recent evidence has shown that cell projections "grow" by polymerization along the advancing boundary of the cell. Together, these characteristics represent a local growth process pinned to the interfacial contour of a contractile network. As such, the moving boundary becomes tractable, but subtle features of the motion lead to specific requirements for the chemical nature of the boundary polymerization process. To demonstrate these features, simple examples for limiting conditions of substrate interaction (i.e., "strong" and "weak" adhesion) are compared with data from experimental studies of yeast particle engulfment by blood granulocytes and actin network dynamics in fishscale keratocytes. PMID- 8494987 TI - Regulation of adenine nucleotide concentration at endothelium-fluid interface by viscous shear flow. AB - The action of adenine nucleotides on vascular endothelial cells is apparently mediated by the local flow conditions. Because nucleotides are sequentially degraded from ATP-->ADP-->AMP-->adenosine by ecto-enzymes at the endothelial surface, it has been hypothesized that the observed flow effect is caused by the flow-dependent change of nucleotide concentration at the cell surface. In this study, we have calculated the concentration profiles of adenine nucleotides at the cell surface under flow conditions encountered in an in vitro parallel-plate flow system, as has been used in several related experimental studies. When medium containing uniformly distributed ATP is perfused over endothelial monolayers, our results show that ATP concentration in the cell vicinity gradually decreases in the streamwise direction as a result of enzymatic degradation. This hydrolysis of ATP results in the generation of ADP, and ADP concentration in turn gradually increases at the cell surface. The concentration profiles of nucleotides are dependent on the levels of applied wall shear rate. As the corresponding shear stress increases from 0.1 to 30 dynes/cm2, ATP concentration at the cell surface at the center of coverslip increases from 0.66 to 0.93. Under no-flow conditions, our model predicts a steady decline of ATP concentration and a transient increase of ATP-derived ADP, comparable to the published results of previous experiments. These numerical results, combined with our recent experimental data, provide insights into the cellular mechanisms by which hemodynamic flow modulates the effects of vasoactive agents on endothelium. PMID- 8494988 TI - Ca transients in cardiac myocytes measured with a low affinity fluorescent indicator, furaptra. AB - Intracellular calcium ion ([Ca2+]i) transients were measured in single rat ventricular myocytes with the fluorescent indicator furaptra. Cells were voltage clamped with a single patch electrode containing the K+ salt of furaptra and fluorescence at 500 nm was measured during illumination with 350 and 370 nm light. Depolarizing voltage-clamp pulses elicited [Ca2+]-dependent fluorescent transients in 30 of 33 cells tested. The peak change in [Ca2+]i elicited by 50-ms depolarizations from -70 to +10 mV was 1.52 +/- 0.25 microM (mean +/- SEM, n = 7). The size of the [Ca2+]i transient increased in response to 10 microM isoproterenol, prolongation of the depolarization, and increasing pipette [Na+]. Because furaptra is sensitive to Ca2+ and Mg2+, changes in [Mg2+]i during the [Ca2+]i transient could not be measured. Instead, a single-compartment model was developed to simulate changes in [Mg2+] during [Ca2+] transients. The simulations predicted that a 2 microM [Ca2+] transient was accompanied by a slow increase in [Mg2+] (14-29 microM), which became larger as basal [Mg2+] increased (0.5-2.0 mM). The [Mg2+] transient reached a peak approximately 1 s after the peak of the [Ca2+] transient with the slow changes in [Mg2+] dominated by competition at the Ca2+/Mg2+ sites of Troponin. These changes in [Mg2+], however, were so small and slow that they were unlikely to affect the furaptra fluorescence signal at the peak of the [Ca2+]i transient. The [Ca2+]i transient reported by furaptra appears to be larger than that reported by other Ca2+ indicators; however, we conclude this larger transient is at least as accurate as [Ca2+]i transients reported by the other indicators. PMID- 8494989 TI - Fast desensitization of the response to InsP3 in Limulus ventral photoreceptors. AB - In Limulus ventral photoreceptor cells the time-course of the desensitization of InsP3 response was measured by an injection-pair paradigm. Pressure pulses of InsP3 were delivered into the cell with various interpulse intervals. The desensitization of the response to the second injection of each pair approached totality at 200 ms, which is the duration of the response to a single pressure pulse of InsP3. Lowering extracellular calcium did not affect the time-course of the desensitization. Lowering the temperature slowed down both the time-course of the response to InsP3 and the time-course of the desensitization to the same extent. These findings suggest that the desensitization is powerful enough and its onset fast enough to contribute to the transience of the InsP3 response. The time-course of the desensitization suggests it may influence light adaptation. PMID- 8494990 TI - The effect of hydration on the dynamics of trimethoprim bound to dihydrofolate reductase. A deuterium NMR study. AB - To determine the effect of hydration on the dynamics of a protein complex, we used deuterium nuclear magnetic resonance (NMR) techniques to examine a trimethoprim (TMP)/E. coli dihydrofolate reductase (DHFR) complex in its lyophilized, partially hydrated, polycrystalline, and ammonium sulfate precipitated states. The results indicate that TMP is rigid in the lyophilized powder state. The dynamic behavior could be restored by partial rehydration. At 30 wt% hydration the deuterium spectrum of the partially hydrated sample was indistinguishable from that of the polycrystalline and ammonium sulfate precipitated samples, suggesting that the structure of the protein/TMP complex is similar in the three physical states. Furthermore, we found that the para- and meta-methoxyl groups have very different dynamical behavior. PMID- 8494991 TI - Action mechanism of idarubicin (4-demethoxydaunorubicin) as compared with daunorubicin in leukemic cells. AB - To characterize a new anthracycline agent, idarubicin (4-demethoxydaunorubicin) and to establish its reasonable and appropriate use in the chemotherapy of acute leukemia, we examined its mode of action and compared it with the results obtained for daunorubicin. Idarubicin was shown to have the characteristic features of the action mechanism of anthracyclines, such as having a strong binding capacity to DNA, in terms of frequency and efficiency and reducing the template activity of DNA by binding to DNA or inducing DNA strand breaks in leukemic cells and inhibiting the DNA polymerase reaction. Idarubicin was superior to daunorubicin in terms of intracellular accumulation and binding capacity to DNA, which may result in idarubicin having much stronger activity in inducing DNA strand breaks than daunorubicin. These excellent properties of idarubicin were considered to explain idarubicin having stronger antileukemic effects than daunorubicin. The efficacy of idarubicin in multidrug-resistant cells is also discussed. PMID- 8494992 TI - Multiple and heterogeneous patterns of cytokine production in 18 leukemia and in vitro transformed mature T cell lines reflect the individuality of human leukemias. AB - The relationship between cytokine production patterns and immunophenotype marker profiles was studied in a panel of 18 T cell lines originating from various types of hematological malignancies and from human T cell lymphotropic virus-I (HTLV-I) transformed cells. The production of 11 different cytokines by both unstimulated and phytohemagglutinin (PHA)-stimulated cells was tested. The production of interleukin-1 alpha (IL-1 alpha), IL-2, IL-3/granulocyte-macrophage colony stimulating factor (GM-CSF), IL-4, IL-5, IL-6, tumor necrosis factor-alpha (TNF alpha), TNF-beta and interferon-gamma (IFN-gamma) by some of the cell lines was detected, and no cell line produced IL-1 beta or IFN-alpha. All 4 cell lines producing IL-1 alpha also produced other inflammatory cytokines, namely, IL-6, TNF-alpha and TNF-beta, but they did not produce IL-2. The IL-1 alpha-producing cell lines had the phenotype of mature, activated T cells, regardless of leukemia or transformant origin (TdT-, CD4+, CD8-, IL-2R+, HLA-DR+) and all were HTLV-1+. However, the production of other cytokines followed a random distribution, and no relationship emerged between cytokine production patterns and alpha/beta or gamma/delta type of T cell receptor (TcR) expression, immunophenotypic marker profiles, or the clinical origin of the cells. These results thus show that human leukemia and HTLV-I-transformed T cell lines can produce a large number of biologically active cytokines and that, except for the association of inflammatory cytokine production with mature activated cells, random patterns of cytokine production reflect the individuality of leukemia cell lines. PMID- 8494993 TI - Serum levels of tumor necrosis factor and soluble interleukin 2 receptor as markers of disease activity and prognosis in childhood leukemia and lymphoma. AB - The serum levels of soluble interleukin 2 receptor (SIL-2R) and tumor necrosis factor (TNF) were assessed in 69 children from 6 months to 14 years old who suffered from acute lymphoblastic leukemia (39), Hodgkin's disease (15), non Hodgkin's lymphoma (15) and in 54 normal age-matched controls prior to any therapy and at remission. Both SIL-2R and TNF levels were significantly higher at diagnosis compared with normal controls (P < 0.001), but decreased significantly at remission. The SIL-2R and TNF levels were significantly higher in an advanced stage of lymphoma than in an early stage. In the patients with acute lymphoblastic leukemia (ALL) and lymphoma, higher levels of SIL-2R (> 1030 units/ml) and TNF (> 30 pg/ml) were associated with a poorer treatment outcome (P < 0.01). Our findings indicate that elevated TNF serum secretion together with SIL-2R are useful markers in childhood ALL and lymphoma and can be used to assess both disease activity and prognosis in this group of malignancies. PMID- 8494994 TI - Variant von Willebrand disease with defective binding to factor VIII: the first case from Japan. AB - This is the first case of variant von Willebrand disease (vWD) with defective binding of von Willebrand factor (vWF) to factor VIII (F.VIII) to be diagnosed in Japan. An 8-year-old Japanese girl, who had had recurrent episodes of subcutaneous hematomas, showed a prolonged A-PTT, low F.VIII (F.VIII:C 4 U/dl, FVIII:Ag 4 U/dl), and normal level of vWF (RCof 80 U/dl, vWF:Ag 60 U/dl). The patient's vWF-multimeric structure on SDS agarose gel electrophoresis was similar to that in normal subjects. A F.VIII binding assay was performed, as described by Nishino et al. (1989). F.VIII binding (y) of vWF was expressed as a function of the amount of immobilized vWF (x) on the wells of a polystyrene plate. Regression lines from normal subjects and the patient had a high correlation coefficient. F.VIII binding capacity was estimated by the slope of the regression lines. The slope for normal subjects showed y = 0.002 + 0.653x, while, in contrast, the slope for the patient showed y = 0.005 + 0.009x, indicating that the capacity of vWF from the patient to bind F.VIII was markedly decreased. Exons 18-20 of the vWF gene, covering the first 132 amino acids of mature vWF subunit from the patient, were sequenced, using the PCR amplification method. A point mutation C- >T at codon 816 in exon 19, predicting a substitution of Trp for Arg(53), was characterized; this was inherited by the patient from her mother. PMID- 8494995 TI - Ten-year complete remission in an 84 year-old patient with acute myeloid leukemia. AB - We report an unusual case in which complete remission of acute myeloid leukemia (AML) had lasted for almost 10 years in a patient who was 94 years and 7 months old as of September 1989. An 84 year-old man was admitted to our hospital with gingival bleeding on October 15, 1979. Hematological data were: RBC 327 x 10(4) microliters, hemoglobin concentration 10 g/dl, platelets 3.8 x 10(4) microliters and WBC 9000 microliters, including 34% blastic cells. Bone marrow aspiration showed nucleated cells 48.0 x 10(4)/microliters with 69.2% blastic cells. He was diagnosed as having AML (M2). Induction chemotherapy consisted of daunorubicin, cyclocytidine, an anhydride analogue of cytosine arabinoside, and prednisolone (DCP). Complete remission was achieved after 1 month of this therapy. After two cycles of consolidation therapy (DCP), intensification therapy (DCP) was performed twice. Thereafter, complete remission lasted without any further therapy, up to September 1989, when he died of pancreatic cancer. The prolonged disease-free survival in this extremely aged patient was attributed to the high sensitivity of leukemic cells to DCP therapy and his good performance status at the time of initial induction chemotherapy. This is the oldest patient with long term remission, lasting for over 5 years, to be reported in Japan. If an elderly patient with typical acute leukemia has a good performance status, intensive chemotherapy should be tried at least once, while carefully controlling complications specific to the elderly. PMID- 8494996 TI - Telomere reduction in hematologic cells. AB - The broken ends of chromosomes are unstable, and tandem fusion of telomeres has been observed in some tumors. Using Southern blot analysis, we report here telomeric DNA changes in hematologic cells. There was some variation in the length of the telomeric DNA in normal peripheral blood mononuclear cells obtained from four different individuals, ranging from 10 to 12 kilobases (kb), but there was little difference in signal strength. In two cell lines tested, HL-60 and K562, there was a telomeric sequence reduction of 2-4 kb and there was also a diminution of signal intensity. Reduction of the telomeric DNA array was also observed in two leukemic cases tested. The peak telomere length of the leukemic cells was 5 and 4 kb before and 10 and 7 kb after treatment, respectively, and in one case there was also a reduction in copy numbers of about 50%. Since no remarkable changes were detected in the Alu and alphoid sequences in either normal or leukemic cells, it appeared that the DNA change was specific to telomeric regions. Assessment of telomeric DNA changes may aid in determining the biological significance of leukemic cells. PMID- 8494997 TI - Rare discovery of paroxysmal nocturnal hemoglobinuria patients with B blood group antigen. PMID- 8494998 TI - Myelodysplastic syndromes: from morphology to molecular biology. Part I. Classification, natural history and cell biology of myelodysplasia. AB - The myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic disorders predominantly affecting the elderly. Patients frequently develop acute leukemia, but the majority suffer from the consequences of bone marrow failure. The underlying acquired genetic abnormality is the inadequate production of dysplastic and poorly functional cells resulting from defective differentiation and premature cell death of the abnormal hematopoietic clone. Although the pathogenesis is unknown, recent evidence suggests that a sequence of DNA lesions leads to alteration of the cellular function, emergence and consequent evolution of the premalignant clone. PMID- 8494999 TI - Myelodysplastic syndromes: from morphology to molecular biology. Part II. The molecular genetics of myelodysplasia. AB - Most studies of the clonal origin of the underlying lesion(s) and all investigations using X-inactivation, have concluded that the myelodysplastic syndromes arise from a multipotent stem cell. Non-random chromosomal abnormalities, particularly deletions of 5q and 7q, are common, most notably in therapy related MDS. Progression to AML is also frequently accompanied by increased genomic instability as evidenced by the emergence of multiple karyotypic abnormalities. While some evidence hints at the presence of tumour suppressor genes on chromosomes 5, 7, 20 and 12, no such genes have yet been identified. The search for point mutations in known oncogenes has concentrated on two oncogenes RAS and c-FMS. Point mutation frequency generating active forms of RAS oncogenes is approximately 40% in MDS overall, up to 80% in studies of CMML. 60% of all MDS RAS mutation involves a G to A transition, producing a substitution of aspartate for glycine at a frequency of 50% (of total ras mutants). RAS mutation is associated with progression to AML, although the presence of a RAS point mutation alone is neither necessary nor sufficient for leukaemic transformation. Mutation of c-FMS is also more common in CMML in comparison to other MDS subtypes and, as yet, point mutation potentiating the response of the receptor to CSF-1 (codon 969) has been found more frequently than point mutation resulting in permanently activated receptor (codon 301). However, recent work has identified additional mutations which produce transforming proteins, and mutation rates at these sites may be relevant in MDS. PMID- 8495000 TI - Menstrual disorders due to chemical exposure among hairdressers. AB - Menstrual disorders may be caused by chemical agents such as organic solvents. Hairdressers are exposed to a multitude of chemical agents suspected to influence the hypothalamus-pituitary-ovarian axis. To investigate the risk of hairdressers for menstrual disorders, female hairdressers were compared to a reference group of clothing saleswomen. Data collection was performed by use of a questionnaire. After excluding women using oral contraceptives, 194 women were available for data analysis. Significant associations were found for irregular cycles, oligomenorrhoea, long blood loss, heavy pains and long pains after confounding correction. No statistically significant association was found for the premenstrual syndrome. It is concluded that hairdressers might have an increased risk for menstrual disorders, but further studies are needed. PMID- 8495001 TI - HIV testing and life insurance. PMID- 8495002 TI - Biological exposure and effect limits. PMID- 8495003 TI - The tools of the trade. PMID- 8495004 TI - Occupational medicine--let's keep our white coats and stethoscopes. PMID- 8495005 TI - Mental health at work--why is it so under-researched? PMID- 8495006 TI - An evaluation of the Reflotron for the determination of plasma cholesterol in capillary blood. Effect of operator variability. AB - The availability of portable analysers potentially puts the detection of individuals with high serum cholesterol levels on a similar footing to that of high blood pressure. The Reflotron, which can make cholesterol measurements on capillary blood samples without the need for centrifugation, has been evaluated in clinical practice. In 94 consecutive patients capillary blood was used for the determination of serum cholesterol by the Reflotron, by a laboratory technician (n = 37) and by a nursing sister (n = 57). Venous blood was also taken from the same patients within a few minutes of the capillary sample for enzymic determination of serum cholesterol at the hospital laboratory. Overall, the Reflotron values were about 0.6 mmol/l lower than those obtained at the hospital laboratory. The accuracy and precision of the results obtained by the nurse were poorer than those obtained by the technician, even though the nurse had attended a three day training course. Our results indicate that the Reflotron is a suitable instrument for use in screening for serum cholesterol, provided personnel operating the machine have adequate training and experience, and provided it is borne in mind that the results obtained may be slightly lower than standard laboratory methods. PMID- 8495007 TI - Back pain and its correlates among workers in family care. AB - In order to assess the prevalence of back pain problems among family care workers, and the association of back pain with selected variables, a cross sectional survey among the 4723 employees of the largest Flemish organization for family care was conducted. A self-administered questionnaire comparable to the standardized Nordic questionnaire on musculoskeletal symptoms was distributed to all employees of the organization. The response rate was 90 per cent (n = 4256) and the study population was almost uniformly composed of females (99.8 per cent). The period prevalence (12 months) amounted to 63 per cent (95 per cent CI: 61.7-64.6) and the point prevalence to 18 per cent (95 per cent CI: 16.5-18.8). Among the respondents suffering from back pain during the past year, 72 per cent suffered from repeated episodes of pain. In 82 per cent low back pain was involved. Twenty-nine per cent of the complaints interrupted their work during the past year, yielding a total number of 23,396 days of sick leave. The mean sick leave for back pain was 36 days and the median 15 days. The frequency of back pain was found to vary according to the regional departments to which the employees belonged, some sections experiencing up to 36 per cent higher period prevalences than the units with the lowest figures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495008 TI - Effects of a 10-week exercise intervention programme on exercise and work capacities in Belfast's ambulance-men. AB - The objective of the present study was to investigate the occupational benefits of an exercise intervention programme, including changes in physical working capacity and other physical fitness measures on a group of Belfast ambulancemen. Physical training was performed twice weekly for 10 weeks and consisted primarily of indoor soccer and circuit-training sessions. Both experimental (n = 8) and control subjects (n = 6) were assessed for height (HT), weight (WT), body composition (percentage fat), standing broad jump (SBJ), flexibility (Flex), and sit-up performance (SU). The experimental group was further assessed for blood pressure (BP), hand grip strength (HGS), maximal oxygen consumption (VO2 max), end lactate concentration (EL), anaerobic threshold (AT) and leg strength (LS). Working capacity was also assessed during a staged emergency incident, using a portable telemetric gas analyser. Significant changes in the experimental group were found following training for Flex, SU, SBJ, VO2 max (all P < 0.05), EL and AT (P < 0.01). A significant drop in the metabolic cost of the simulated emergency incident was also noted following training. No significant differences were found for the control group over the experimental period. The present study indicated that a twice-weekly exercise intervention programme was effective in improving the physical fitness of Belfast's ambulancemen. Such a programme could prove cost-effective by increasing work capacity and decreasing absenteeism related to musculoskeletal injury. PMID- 8495009 TI - Control of infection in an international airline. AB - The paper examines the possible sources of infection on an international aircraft, including the provision of food, the supply of drinking water, and the removal of waste. It considers aspects of control, and explains some of the steps which have to be taken by a major international carrier to ensure that the high quality expected by the customer is provided in all areas of the world, even those where natural resources and expertise may be limited. The emphasis is on providing a safe product, and removing any possible risk of infection of the passengers. PMID- 8495010 TI - Relationship between atmospheric and urinary nickel in workers manufacturing electrical resistances using nickel oxide: role of the bioavailability of nickel. AB - The daily concentrations of nickel in total (ie inhalable) and respirable airborne dust (personal sampling) and in post-shift and pre-shift urine samples were monitored during five consecutive work days in 20 workers exposed to NiO in a workshop manufacturing electrical resistances. The individual daily atmospheric nickel concentrations ranged from 0.5 to 9586 micrograms Ni/m3 (geometric mean 22.9) for total dust and from 0.2 to 332 micrograms Ni/m3 (geometric mean 3.5) for respirable dust. The results of the urinary excretion of nickel suggested that the occupationally-related systemic absorption of nickel strongly differed in one subject (worker E) compared to the other 19 workers. In the latter group the nickel concentration in urine never exceeded 5 micrograms Ni/g creatinine, it did not differ between post-shift and pre-shift samples (geometric means: 1.1 versus 1.2 micrograms Ni/g creatinine), and it was only slightly higher than that measured in a group of 17 non-exposed subjects (mean 0.5 micrograms Ni/g creatinine; range 0.1-1.7); furthermore their nickel elimination in urine did not change during the days off or after two weeks of holiday. In worker E, the nickel concentration ranged from 21 to 101 micrograms Ni/g creatinine in post-shift urine, the next morning (after 16 h) it had dropped on average by 50 per cent, it decreased further during the days off, and amounted still to 4.4 micrograms Ni/g creatinine after two weeks of holiday. These divergent patterns of elimination of nickel in urine are most likely related to differences in the nature of exposure to airborne nickel involving both particle size and bioavailability of nickel. Worker E was exposed to NiO powder of 1-8 microns particle size resulting in nickel levels of the respirable fraction on average about 50 times that measured for the 19 other workers (3 micrograms Ni/m3). Transformation of the initial NiO powder into particles of 150 to 600 microns size and associated changes in physicochemical properties of NiO in the particles of the respirable fraction may explain why the urinary excretion of nickel in the 19 workers is hardly influenced by their occupational exposure to this metal. The pattern of urinary nickel elimination in worker E, however, most likely reflects very recent exposure to NiO, suggesting that the degree of bioavailability of nickel from this particular physicochemical form of NiO powder is much higher than that usually accepted for poorly soluble nickel compounds. PMID- 8495011 TI - Acute respiratory infections: a high priority. The Working Group on ARI, Respiratory Disease Committee. PMID- 8495012 TI - Incidence of abdominal tuberculosis in Bangladeshi migrants in east London. AB - A retrospective epidemiological study of abdominal tuberculosis in a defined population in the London Borough of Tower Hamlets was conducted between January 1985 and 31 December 1989. The total population of 163,900 included a mean of 20,732 Bangladeshis. Of the 13 cases diagnosed 8 were Bangladeshi, with equal involvement of the peritoneum and intestine. The crude incidence in the Bangladeshi community was 7.7 cases/10(5)/year, which was significantly higher than that in Europeans (0.3 cases/10(5)/year, chi 2 with Yate's correction = 14.0 P < 0.001). The highest age-specific incidence was amongst those aged 16-20 years and 41-45 years. Most patients had a laparotomy or peritoneal biopsy to confirm the diagnosis. The response to therapy was good. Only 62% of cases were notified. This study confirms the importance of tuberculosis in the differential diagnosis of abdominal symptoms in Bangladeshi patients. PMID- 8495013 TI - Utilization of antituberculosis drugs expressed in defined daily doses in Klenovnik Hospital in the period between 1983 and 1987. AB - In this paper the utilization of antituberculosis drugs was analyzed in defined daily doses per 1000 bed-days (DDD/1000 BD) in the Hospital for Pulmonary Diseases and Tuberculosis, Klenovnik, from 1983 to 1987. The utilization of these drugs increased from 894 DDD/1000 BD in 1983 to 1112 DDD/1000 BD in 1984, and then decreased to 1077 DDD/1000 BD in 1986; but in 1987 it again increased to 1270 DDD/1000 BD. During the research period the following drugs were prescribed: ethambutol, rifampin, pyrazinamide, streptomycin, isoniazid, and two combinations of drugs: a combination of isoniazid with pyridoxine and a combination of ethambutol, isoniazid and pyridoxine. For the whole of that period the use of ethambutol, isoniazid with pyridoxine and rifampin made up more than 85% of the general utilization of antituberculosis drugs, while other drugs were prescribed in lesser quantities. The data presented indicate that tuberculosis in Klenovnik hospital was in most cases treated with ethambutol, the combination of isoniazid with pyridoxine, and rifampin. PMID- 8495014 TI - Acute respiratory infections: conclusions of an IUATLD workshop. The Working Group on ARI, Respiratory Disease Committee. PMID- 8495015 TI - Tuberculin reaction in pulmonary tuberculosis in the Asir Region of Saudi Arabia. AB - The Mantoux test was performed on 75 Saudi and Yemeni patients with pulmonary tuberculosis using 2TU of PPD-RT23; 82.7% of these patients had a positive skin test. It was also noted that, contrary to findings in the West, old age does not seem to affect the Mantoux reaction adversely. 9 patients had a non-significant reaction and using the 3-step 'boosting', 8 of the 9 (88.9%) non-reactors converted to positive. Despite the low number of patients included in our study, we recommend 3-step 'boosting' when doing tuberculin skin testing in Third World Countries in order to bring out the true tuberculin 'reactors'. PMID- 8495016 TI - Bacteriological investigations for short-course chemotherapy under the tuberculosis programme in two districts of India. AB - To examine the bacteriological profile and the prevalence of drug resistance among patients attending the health facilities where the District Tuberculosis Programme (DTP) was in operation with short-course chemotherapy (SCC) regimens, sputum specimens were collected on admission and the end of treatment in North Arcot district and Pondicherry region. In North Arcot district, rifampicin, isoniazid and pyrazinamide were given twice weekly for the first 2 months followed by rifampicin and isoniazid twice a week for the next 4 months under fully supervised administration. In Pondicherry, rifampicin, isoniazid and pyrazinamide were given daily for the first 2 months followed by rifampicin and isoniazid twice weekly for the next 4 months. Of the patients who had received 80% or more of the drugs, 80% from North Arcot and 92% from Pondicherry were rendered culture-negative for Mycobacterium tuberculosis at the end of treatment. Even among patients with initially resistant bacilli, a high proportion had a favourable response. Before start of treatment, of the 2779 patients from North Arcot, 25% had resistance to one or more drugs including 2% with resistance to rifampicin. In Pondicherry, 13% of the patients had initial resistance to one or more drugs. Initial resistance to rifampicin was observed in 0.9%. None of the initially drug-sensitive patients had acquired resistance to rifampicin at the end of treatment. PMID- 8495017 TI - Evaluation of the efficacy of health education on the compliance with antituberculosis chemoprophylaxis in school children. A randomized clinical trial. AB - Chemoprophylaxis against tuberculosis with isoniazid for 1 year is very useful, but patient compliance is very low. A controlled clinical trial was performed to evaluate the efficacy of three alternative health education strategies and to observe which of them improves compliance with antituberculosis chemoprophylaxis in healthy tuberculin-reactor children. Although all three strategies achieved positive, statistically significant results as compared with the control group, that performed by nursing personnel at the patient's home is the most effective, followed by that performed by the same health professionals by telephone. The least effective strategy by far was that performed by the physician in his surgery. PMID- 8495018 TI - Factors associated with compliance in treatment of tuberculosis. AB - The most important cause of failure of antituberculosis therapy is that the patient does not take the medication as prescribed. To assess this problem, a retrospective review was conducted, using medical and nursing records, of adult patients treated at the tuberculosis clinic of the Montreal Chest Hospital in 1987-1988. In all, 352 patients were identified, of whom 59% were judged to have completed therapy. Completion of therapy was recorded in 92% of those with culture-positive disease, 76% of those with active but culture-negative disease and 54% among the 300 prescribed preventive therapy (P < 0.001). Compliance with preventive therapy was highest among those who had been in contact with an active case, and lowest among those identified through a workforce screening survey (P < 0.01). At the time of the first follow-up visit, patients identified to have suboptimal compliance were more likely to fail to complete therapy (P < 0.001). Compliance was higher among those initially hospitalized, those assessed to have better understanding (P < 0.05), those prescribed 6-9 rather than 12 months of therapy (P < 0.01), and those who returned for follow-up within 4 weeks of initiation of therapy (P < 0.01). Compliance could be improved by enhancing patient understanding, closer follow-up, and shorter therapy, particularly for those at lower risk of reactivation. As well, additional compliance enhancing interventions can be targeted to those patients with suboptimal compliance who can be accurately identified early in the course of therapy. PMID- 8495019 TI - BCG-induced protection in guinea pigs vaccinated and challenged via the respiratory route. AB - Since studies on cellular immune responses have demonstrated the role of the mucosal lymphoid system of the respiratory tract, we have studied responses obtained from the local respiratory route, compared to the systemic intradermal route, of BCG immunization. Guinea pigs vaccinated with different doses of BCG via both routes served to follow lymphoid cell proliferation, hilar lymph node and lung BCG clearance, lung granuloma formation and protection induced after virulent challenge. Results demonstrate that the aerogenic route of vaccination with BCG has no harmful side-effects for the host. In comparison with the intradermal route of vaccination, aerogenic vaccination with 10(5) BCG cfu induced higher local cellular immune responses and a substantially improved protective effect. PMID- 8495020 TI - Congenital tuberculosis. AB - A neonate presented with poor feeding, jaundice and hepatosplenomegaly. He was in liver failure with disseminated coagulopathy. Post-mortem liver biopsy revealed discrete granulomas with central necrosis and acid-fast bacilli on Ziehl Nielsen's stain. The mother had active tuberculosis at delivery. The principal characteristics of congenital tuberculosis are reemphasized in this observation. PMID- 8495021 TI - Corticosteroids and tuberculosis: risks and use as adjunct therapy. AB - Adjunct therapy with corticosteroids, in conjunction with antituberculous drugs, may be appropriate in particular forms of tuberculosis. Prospective controlled trials have shown a benefit in tuberculous meningitis, pericardial and pleural disease. Although benefit has been shown in pleural disease, adjunct therapy is not routinely required unless there are significant systemic symptoms of fever or a particularly large effusion. It has been recommended in the past that corticosteroids should be used routinely in endobronchial TB, especially pediatric disease, but our recent experience has been that such therapy is not usually required. Although corticosteroid therapy is sometimes recommended in extensive pulmonary disease there are no controlled trials, in the modern drug era, to support such therapy. Where adrenal suppression is a concern supplemental corticosteroids are indicated. Fever, be it drug-related or from systemic disease, sometimes requires suppression with corticosteroids. The usual dose required is 40-60 mg of prednisone orally daily for 4-6 weeks depending on the system involved, with tapering doses of prednisone subsequent to this. Local corticosteroid therapy of BCG-related keloid reactions may also be useful. Anecdotal reports suggest immune suppression with corticosteroids predisposes to tuberculosis but retrospective studies on patients taking, in general, low doses of prednisone have not confirmed this risk. Corticosteroid interaction with the oral birth control pill and rifampin need also to be accounted for in prescribing these agents. PMID- 8495022 TI - Detection of nitrate reductase activity of mycobacteria: an evaluation of the use of a powdered reagent in the test, and rapid swab methods as compared to the conventional test. AB - Tests using a powdered reagent proved to be an excellent alternative to the test using conventional reagents for the detection of nitrate reductase activity of mycobacteria. A rapid swab test, using either a dry or moist swab, showed inferior results to the conventional test. PMID- 8495023 TI - A rare location of extrapulmonary tuberculosis: the vulva. PMID- 8495024 TI - Resistant tuberculosis: successful treatment with amikacin, ofloxacin, clofazimine, and pas. PMID- 8495026 TI - The language of epidemiology. (XVI): Cohort studies. PMID- 8495025 TI - Drug resistance in tuberculosis: it's not always the patient's fault! PMID- 8495027 TI - For the benefit of the sick: lessons from the Travelers Aid Medical Van. PMID- 8495028 TI - Orbis International: a chance to give. PMID- 8495029 TI - Amos House: a place for the homeless and hungry. PMID- 8495030 TI - Physicians for peace: making a difference in the West Bank. PMID- 8495031 TI - Chad Brown Health Center and physician volunteering. PMID- 8495032 TI - Volunteerism in the Naval Reserve: a 15-year perspective. PMID- 8495033 TI - Caring for the Romanian orphans. PMID- 8495034 TI - Rhode Island's first woman physician. 1971. PMID- 8495035 TI - Eye care for persons with diabetes in Rhode Island. PMID- 8495036 TI - Correlation of nonspecific bronchial responsiveness to baseline pulmonary function in patients with asthma and sinobronchial syndrome. AB - To examine the relationship of nonspecific bronchial responsiveness to baseline pulmonary function, and to compare the reactivity in asthma and sinobronchitis, we measured the provocative concentration of methacholine, causing a 20% fall in forced expiratory volume in one second (PC20-FEV1) in 82 asthmatic patients, 54 patients with sinobronchial syndrome and 57 normal subjects. Log PC20-FEV1 was directly correlated to baseline pulmonary function. The strongest correlation was seen between log PC20-FEV1 and baseline FEV1 as a % of the predicted FEV1 (%FEV1), both in asthma (log PC20-FEV1 = 0.020 x %FEV1-1.988, r = 0.54, p < 0.01) and in sinobronchial syndrome (log PC20-FEV1 = 0.025 x %FEV1-1.233, r = 0.64, p < 0.01). From the regression equations, the mean value of PC20-FEV1 at 100% FEV1 was calculated as 1.02 and 18.5 mg/ml in asthmatic and sinobronchitic patients, respectively, and the value was 35.5 mg/ml in normal subjects. The PC20-FEV1 to %FEV1 relationship may be helpful to assess individually measured PC20-FEV1 values in patients with airway obstruction. PMID- 8495037 TI - Reduction of increased signal intensity in the basal ganglia on T1-weighted MR images during treatment of hepatic encephalopathy. AB - A 61-year-old man with liver cirrhosis showed a symmetrical increase in the signal intensity of the basal ganglia on T1-weighted magnetic resonance (MR) images, which was diminished after 3 months of treatment for hepatic encephalopathy. He recovered from encephalopathy with treatment, and liver dysfunction (hyperammonemia and abnormal blood coagulation) as well as the results of quantitative psychometric tests showed a marked improvement. The cause of these high signal intensity changes on T1-weighted images and the reason for their partial reversibility are not known, but hyperammonemia due to portal systemic shunting might be closely related to these clinical observations. PMID- 8495038 TI - Sarcoidosis accompanied by pancreatic impairment. AB - A 64-year-old male complained of weight loss and slight fever. Bilateral hilar lymphadenopathy and hepato-splenomegaly were observed. Serum ACE level was high, and liver function was impaired. Laparoscopy demonstrated small white nodules on the liver surface. A definite diagnosis of sarcoidosis was made by histological study of the specimen by liver biopsy and noncaseating epithelioid cell granulomas composed of giant cells and epithelioid cells were revealed. Various pancreatic enzymes were increased on admission, suggesting pancreatic impairment due to sarcoidosis. Corticosteroid therapy improved liver and pancreatic functions and decreased splenomegaly. He has been followed up for 4 years and 5 months. PMID- 8495039 TI - Autoimmune hepatitis and hypothyroidism associated with anti-thyroid hormone autoantibodies. AB - A 40-year-old hypothyroid female who had been treated with synthetic thyroxine was admitted to our hospital in October 1988 due to abnormal liver function tests. She had low serum free triiodothyronine (T3; 2.3 pg/ml) and high serum thyrotropin (TSH; 20.8 microU/ml) concentrations. On the other hand, the serum free thyroxine (FT4) level was inappropriately high, being 2.46 ng/dl. Immune precipitation of radiolabeled thyroid hormones with her serum disclosed the binding of 125I-T3 and 125I-T4 to the extent of 9.5% and 11.3%, respectively (normal ranges for 125I-T3 and 125I-T4 binding are less than 6.3% and 5.9%, respectively). 125I-T4 binding to the patient's serum gamma globulin was completely displaced with the addition of unlabeled T4. Further examination disclosed that anti-T4 antibodies in her serum belong to IgG kappa class immunoglobulin. PMID- 8495040 TI - Alport syndrome diagnosed by immunofluorescence using a new monoclonal antibody. AB - A 14-year-old female with microscopic hematuria was admitted for a renal biopsy. She had a family history of renal disease without deafness. The findings of light microscopy and conventional immunofluorescence were normal. Electron microscopy showed a diffuse thinning of the glomerular basement membrane (GBM) with its mild splitting. Irregular thickening of GBM and glomerular small dense particles was not observed. Thin basement membrane syndrome was suspected from these findings. However, it was difficult to differentiate from Alport syndrome. Immunofluorescence analysis using the monoclonal antibody to the 28-kilodalton monomers of the noncollagenous domain of type IV collagen verified the diagnosis of heterozygous Alport syndrome. PMID- 8495041 TI - Reversible acute renal failure in idiopathic nephrotic syndrome. AB - Acute renal insufficiency developed in four idiopathic nephrotic patients with minimal change or mild proliferative glomerulonephritis. The reduction in glomerular filtration rate (CInulin) was not in proportion to the renal plasma flow (CPAH) as evidenced by a low filtration fraction. Diuretic therapy failed to reverse renal insufficiency, and renal biopsy showed no evidence of interstitial nephritis, acute tubular necrosis or interstitial edema. Corticosteroid therapy induced a recovery of renal function with a decrease in proteinuria. These observations suggest that acute renal insufficiency in the idiopathic nephrotic syndrome might be caused by impaired glomerular permeability. PMID- 8495042 TI - Cowden's disease with pulmonary hamartoma. AB - A case of Cowden's disease is reported. A 38-year-old man was admitted to our hospital because of an abnormal left lung shadow on a chest radiograph. There were no symptoms, although the patient had multiple papules on the nose and pharynx mucosa. There were a few fibromas on the axillas and the inguinal regions. The patient had thyroid goiters, gastrointestinal polyposis, and a pulmonary hamartoma. The latter has not been reported previously in Cowden's disease. PMID- 8495043 TI - Hereditary lipo-muscular atrophy with joint contracture, skin eruptions and hyper gamma-globulinemia: a new syndrome. AB - We previously reported two siblings with decreased subcutaneous adipose tissue, muscular atrophy, joint contractures, recurrent skin eruptions, hyper-gamma globulinemia, and reduced natural killer cell activity. Some of their clinical features are similar to those of partial lipodystrophy, but they are distinct in that muscular atrophy, joint contractures and recurrent skin eruptions are not found in patients with partial lipodystrophy. Thirteen other Japanese patients with similar clinical manifestations have been reported. We propose that such cases should be considered a distinct clinical entity. PMID- 8495044 TI - Identification of metastatic carcinoma in the thyroid by determination of thyroglobulin level in aspirates and ultrasonic findings. AB - A 49-year-old female with a metastatic renal cell carcinoma to the thyroid is presented. The thyroglobulin (Tg) level in tumor aspirates of this patient was 37.3 micrograms/l, while that of 49 patients with primary thyroid nodules ranged from 2.0 x 10(3) to 7.5 x 10(8) micrograms/l. Ultrasonogram of the thyroid demonstrated a well-demarcated oval nodule with a cystic region, the solid part of which was hypoechoic and homogeneous. However, similar ultrasonic findings were observed in only 1.1% of 1,054 patients with primary thyroid nodules. Determination of Tg in tumor aspirates and ultrasonography of the thyroid may contribute to the differentiation of metastatic thyroid nodules from primary thyroid nodules. PMID- 8495045 TI - Systemic amyloidosis in a patient with adult onset Still's disease. AB - A 39-year-old woman presented clinical features of adult onset Still's disease. Seven years after the onset, she developed renal insufficiency and biopsy studies revealed amyloid deposits involving amyloid A protein, P component, lambda chain and kappa chain in the kidney and rectum. She died in 1992, primarily due to cardiac failure associated with amyloidosis, indicating that amyloidosis should be considered one of the fatal complications in adult onset Still's disease with a long history. PMID- 8495046 TI - Ankylosing spondylitis successfully treated with methotrexate. AB - A 37-year-old man with ankylosing spondylitis (AS) and psoriasis who was successfully treated with methotrexate (MTX) is reported. In 1980, he had low back pain, limited motion in the lumbar spine, radiological findings of bilateral sacroiliitis, and HLA-B27 positivity. In January 1991, he developed psoriasis and he had difficulty in performing desk work in spite of treatment with antirheumatic drugs. In May 1991, MTX 7.5 mg/week per os was started. Joint symptoms, psoriasis, and acute phase reactants improved within 1 month after the treatment and this improvement continued for more than 6 months after the treatment. After discharge he was able to return to his job. PMID- 8495047 TI - Ectopic choroidal calcification of the eyes of a patient with parathyroid adenoma. AB - A 39-year-old man was admitted to our hospital complaining of general malaise, polyuria, disturbance of ocular movement and right cervical tumor. Blood examination revealed increased parathyroid hormone, hypercalcemia and hypophosphatemia, suggestive of hyperparathyroidism. Histology of the resected tumor revealed a benign parathyroid adenoma. Ectopic calcifications in the choroid and sclera were noted by computed tomography and further ophthalmological examination. Although ocular calcification in conjunctiva and cornea associated with hyperthyroidism is not unusual, sclerochoroidal calcification has not been reported previously in Japan. The possible cause of this unusual condition in this patient is discussed. PMID- 8495048 TI - Hereditary complete thyroxine-binding globulin deficiency: identification by T3 resin uptake test and DNA analysis. AB - Complete thyroxine-binding globulin deficiency (TBG-CD) was uncovered in a subject receiving a comprehensive health examination. The subject had an abnormally high T3 resin uptake. A family study showed that the TBG abnormality had been inherited by X-chromosome linkage. Genetic analysis revealed single nucleotide deletion, common among Japanese with TBG-CD, from the allele specific amplification of the TBG genes of the family. PMID- 8495049 TI - Carney's complex with primary pigmented nodular adrenocortical disease and spotty pigmentations. AB - Carney's complex is composed of myxoma, spotty pigmentation and endocrine overactivity. A 27-year-old male was diagnosed to have Carney's complex on the basis of intense spotty pigmentations on his face, soles and palms, and bilateral adrenal nodular hyperplasia on computed tomography scanning (CT) and magnetic resonance imaging (MRI). Total bilateral adrenectomy was done; histological findings were compatible with primary pigmented adrenocortical disease (PPNAD). Recently, his sister and one of his brothers were suspected to have Carney's complex with PPNAD. We report the first familial case of Carney's complex with PPNAD and spotty pigmentations in Japan. PMID- 8495050 TI - Silent mixed ganglioneuroma/pheochromocytoma which produces a vasoactive intestinal polypeptide. AB - An unusual pheochromocytoma was incidentally discovered in a 48-year-old woman. The patient had a 3-year history of myasthenia gravis. At the time of examination in our hospital, the right adrenal tumor was incidentally discovered by ultrasonography of the abdomen. She had no history of headache, perspiration, palpitation or hypertension. Although blood catecholamine levels were within the normal limits, urinary secretion of catecholamine was elevated. Histologically, the tumor was diagnosed to be mixed ganglioneuroma/pheochromocytoma and histochemically confirmed to produce vasoactive intestinal polypeptide. Such a tumor is quite rare. PMID- 8495051 TI - Rhabdomyosarcoma in the inferior vena cava with secondary Budd-Chiari syndrome. AB - A 63-year-old man with symptoms of obstruction of the inferior vena cava was examined by computed tomography, ultrasound imaging and angiography. Examination revealed a tumor in the inferior vena cava, and transvenous biopsy revealed a rhabdomyosarcoma. The tumor was surgically resected and was easily separated from the surrounding tissues. Nevertheless, a local recurrence developed 43 days after the operation, and the patient's condition deteriorated rapidly. Hepatomegaly and ascites believed to represent the Budd-Chiari syndrome were noted. The patient died on the 163rd postoperative day. Autopsy revealed a tumor extending from the inferior vena cava just above the right renal vein to the right atrium and involving the lobus caudatus of the liver. Clinically, the tumor was thought to have arisen from the middle segment of the inferior vena cava. However, a diagnosis of primary hepatic rhabdomyosarcoma with extrahepatic growth could not be excluded. Only 12 cases of primary liver rhabdomyosarcoma have been reported, and none of those patients demonstrated Budd-Chiari syndrome. Our patient, diagnosed as rhabdomyosarcoma with secondary Budd-Chiari syndrome, is believed to be the first such report. PMID- 8495052 TI - Superior vena cava syndrome due to Graves' disease. AB - We encountered a patient with Graves' disease showing superior vena cava (SVC) syndrome. The patient was a 72-year-old woman with diffuse nontoxic goiter (diagnosed as chronic thyroiditis); she developed Graves' disease during L-T4 administration. Radioiodine-131 therapy failed to give sufficient effect, and the intrathoracic goiter became enlarged in association with increases in thyroid stimulating antibody activities, followed by the development of SVC syndrome. The surgically excised thyroid gland was diffuse without any nodules. Microscopic findings revealed adenomatous hyperplasia. The present case, though extremely rare, seems important for the understanding of the mechanism of onset of SVC syndrome in relation to thyroid gland enlargement. PMID- 8495053 TI - Volatile organic solvents in correction fluids: identification and potential hazards. PMID- 8495054 TI - Residues of benzene in chemical products. PMID- 8495055 TI - Evaluation of modifications of the simple spectrofluorometry method for estimating petroleum hydrocarbon levels in sea water. PMID- 8495056 TI - Effect of herbicide formulation on atrazine residue removal from chemical plant workers' protective clothing. PMID- 8495057 TI - Benomyl toxicity in chickens. PMID- 8495058 TI - Some heavy metals accumulate more in the flesh of Thryonomis swinderianus (Lem), grasscutter, than in beef of Bos species, cow. PMID- 8495059 TI - Effect of grilling, roasting, and cooking on the natural hexachlorobenzene content of ovine meat. PMID- 8495060 TI - Heavy metals in muscle, liver, and kidney from Finnish elk in 1980-81 and 1990. PMID- 8495061 TI - Background levels of PCBs in residents of British Columbia, Canada. PMID- 8495062 TI - Influence of dust from a limestone quarry on chlorophyll degradation of the lichen Physcia adscendens (Fr.) Oliv. PMID- 8495063 TI - Microbial degradative activity in ground water at a chemical waste disposal site. PMID- 8495064 TI - Organochlorine insecticide and PCB residues in two bat species from four localities in Spain. PMID- 8495065 TI - Toxicity studies in fertilized zebrafish eggs treated with N-methylamine, N,N dimethylamine, 2-aminoethanol, isopropylamine, aniline, N-methylaniline, N,N dimethylaniline, quinone, chloroacetaldehyde, or cyclohexanol. PMID- 8495066 TI - Effects of dietary copper and zinc concentrations on feeding rates of two species of talitrid amphipods (Crustacea). PMID- 8495067 TI - Effects of long-term exposure to a mixture of cadmium, zinc, and inorganic mercury on two strains of tilapia Oreochromis niloticus (L.). PMID- 8495068 TI - Contaminants in Missouri River pallid sturgeon. PMID- 8495069 TI - Polycyclic aromatic hydrocarbons in the digestive glands of the American lobster, Homarus americanus, captured in the proximity of a coal-coking plant. PMID- 8495070 TI - Heavy metals in clams from a subtropical coastal lagoon associated with an agricultural drainage basin. PMID- 8495071 TI - Differentiation in copper and nickel accumulation in adult female and juvenile Porcellio spinicornis from contaminated and uncontaminated sites in northeastern Ontario. PMID- 8495072 TI - Persistent organochlorine residues in canned cod-livers of the southern Baltic origin. PMID- 8495073 TI - Vitamin E and liver damage in MZ heterozygous infants with alpha 1-antitrypsin deficiency. AB - Low levels of alpha 1-antitrypsin can predispose affected infants to develop a wide spectrum of liver diseases. Heterozygous PiMZ carriers can be affected by a subclinical liver involvement in the first six months of life. The liver damage appears to be mediated by the activity of toxic oxygen waste products originating from partially unchecked proteases which can cause enough damage to impair hepatic function significantly. In the present study it was found that the antioxidant properties of vitamin E were able to reduce the frequency of liver dysfunction in PiMZ carriers at two but not at five months of age. Liver damage is highly related to low levels of alpha-tocopherol in the plasma. These findings show that oxidative free radicals can promote liver damage in inadequately protected young infants, such as those affected by alpha 1-antitrypsin deficiency. The protective role of vitamin E in relation to the developmental expression of other antioxidant scavengers is discussed. PMID- 8495074 TI - Hospital screening of coeliac disease in Estonian children by anti-gliadin antibodies of IgA class. AB - Seven hundred consecutive patients from Tartu Children's Clinic were screened for coeliac disease by IgA class anti-gliadin antibody enzyme-linked immunosorbent test during January 1 to May 31, 1991. A positive anti-gliadin antibody test result was revealed in 11 children and in 8 coeliac disease was diagnosed according to the criteria of the European Society for Paediatric Gastroenterology and Nutrition. There was no suspicion of coeliac disease before anti-gliadin antibody determinations in five children and two were asymptomatic. In five children, no suspicion of coeliac disease was raised beforehand. The present study shows that coeliac disease is underdiagnosed in Estonia. PMID- 8495075 TI - Compliance in teenagers with coeliac disease--a Swedish follow-up study. AB - A group of 47 children with coeliac disease, born between 1973 and 1978 in the Swedish county of Vastmanland, participated in a controlled questionnaire study. Health, self-esteem, knowledge of the disease and dietary compliance were investigated. The children with coeliac disease were otherwise just as healthy as the control children. Growth and self-esteem were normal. Good knowledge of coeliac disease and dietary treatment was found in 87% of children and dietary compliance was 81%. Girls and younger children (12-14 years) were more compliant than boys and older children (15-17 years). Compliance correlated positively to knowledge. PMID- 8495076 TI - Estimation of annual height velocity based on short- versus long-term measurements. AB - We assessed the relationships between annual height velocity, calculated from two measurements taken at intervals of 6, 12 and 24 months, in 69 healthy prepubertal children (34 male, 35 female) aged 6.5 years (range 6.25-6.75 yrs) who were followed for 2.5 years and measured biannually. Initial height values for age were within normal ranges except for one child with a height SDS of -2.0. Mean annual velocities also conformed to British norms. Significant differences were observed between consecutive six-monthly velocities and these values failed to predict annual velocities calculated from measurements taken at 12- or 24-month intervals. Seasonal effects were thought to have some impact on the six-monthly velocity differences. Height velocity, based on measurements taken at intervals of 12 months, was essentially similar to two-year velocity values. The results indicate that in estimating annual height velocity, six-month intervals between measurements may be misleading while 12-monthly measurements are as reliable as height velocity values based on measurements taken at two-year intervals. PMID- 8495077 TI - Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index. AB - A total of 5473 pharmacological stimulation tests were carried out in 3143 children and subjected to statistical analysis. The mean chronological age of the children was 9 years 9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months (range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625); (2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine (n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7) L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol (n = 815). Measurement of plasma growth hormone was always performed using the same method. The distribution of values in each test was of the gausso-logarithmic type. The results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2) 11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8) 20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity of these tests is low, the mean peak may vary two-fold from one test to another, and the percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The proportion of growth hormone deficiencies thus varies considerably according to the test used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495078 TI - Longitudinal evaluation of glucose tolerance and insulin secretion in non diabetic children and adolescents with cystic fibrosis: results of a two-year follow-up. AB - Thirty-two patients with cystic fibrosis and repeatedly normal fasting blood glucose underwent oral glucose tests and islet-cell antibody assessments on two occasions approximately two years apart. Fourteen patients underwent two iv glucose tolerance tests also. Although in the group as a whole mean glucose areas in response to the oral test remained substantially unmodified over the two-year period, the prevalence of glucose tolerance abnormalities increased from 37.5 to 50%. Insulin output in response to both oral and iv tolerance tests decreased over time. Worsening of insulin secretion and/or of glucose tolerance was never accompanied by deteriorating clinical status. Islet-cell antibodies were detected in no patients, even in those who developed a diabetic glucose tolerance. These results support, on a longitudinal basis, the view of a progressive impairment of B-cell function in cystic fibrosis, which may precede the onset of metabolic abnormalities and is not triggered by autoimmunity. PMID- 8495079 TI - Growth dynamics in cystic fibrosis. AB - The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71-82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity. PMID- 8495080 TI - The LIF test. PMID- 8495081 TI - Growth velocity and serum aminoterminal propeptide of type III procollagen in precocious puberty during gonadotropin-releasing hormone analogue treatment. AB - Growth velocity and serum aminoterminal propeptide of type III procollagen (P-III NP) were evaluated in 11 girls (age 3.8-8.5 years) with central precocious puberty during luteinizing hormone releasing hormone (LH-RH) analogue treatment (D-Trp6-LH-RH, 60 micrograms/kg im for 28 days, n = 7; D-ser(TBU)6-LH-RH, 1600 micrograms/day intranasally, n = 4). Before treatment, growth velocity (10.2 +/- 1.9 cm/year) and P-III-NP concentrations (12.8 +/- 4.3 micrograms/l) were in the pubertal range. During therapy, growth velocity significantly decreased to the prepubertal levels. P-III-NP concentrations decreased significantly after six months of therapy (7.9 +/- 3.7 micrograms/l, p < 0.001). Three girls with low growth velocity ( < 4 cm/year), stimulated growth hormone peak < 10 micrograms/l, and altered 12-h nocturnal growth hormone secretion at 12 and/or 18 months of treatment, had a more marked decrease in P-III-NP concentrations (patient 3: 65.9%; patient 5: -58.7%; patient 10: -61.0%) after 6 months of therapy. Our results suggest that LH-RH analogue treatment in central precocious puberty may impair growth. In these cases, measurement of serum P-III-NP levels may be an additional marker to monitor growth. PMID- 8495082 TI - Acute thrombocytopenic purpura following measles, mumps and rubella vaccination. A report on 23 patients. AB - An acute thrombocytopenic purpura developed shortly after measles-mumps-rubella vaccination in 23 of approximately 700,000 children immunized over a period of seven years. The mean interval from inoculation to the onset of purpura was 19 days. Bone marrow aspirates obtained from 13 patients showed increased or normal amounts of megakaryocytes. Platelet survival time was markedly shortened in the two patients studied. Fifteen patients recovered (the platelet count exceeded 100 x 10(9)/l) in one month, five in two months and two in six months. Increase in platelet-associated immunoglobulin was detected in 10 of 15 patients. Circulating antiplatelet autoantibodies (AAb) against glycoprotein IIb/IIIa were detected in 5 of 15 patients. The findings are compatible with an autoimmune mechanism triggered by immune response to measles-mumps-rubella vaccination. As evaluated by the clinical course and the presence of AAb, post-vaccination thrombocytopenic purpura appears to be indistinguishable from childhood acute idiopathic thrombocytopenic purpura. PMID- 8495083 TI - Fever and neutropenia in children with cancer: diagnostic parameters at presentation. AB - We evaluated 91 episodes of fever in 46 profoundly neutropenic children with cancer, in a search for any symptom, sign or laboratory test that would serve to identify patients with septicemia and differentiate them from those in no immediate need of prompt antimicrobial therapy. Seventeen episodes (19%) were bacteremias, 59 (64%) were suspected septic infections, 9 (10%) were focal bacterial infections and 6 (7%) proved not to be bacterial infections. We were unable to detect any parameter, either on admission or after two days of antimicrobial therapy (except for blood culture findings), that would be helpful in differentiating bacteremia from an episode not of bacterial origin. We focused on serum levels of C reactive protein and found them unreliable on an individual level. Prompt institution of antimicrobial therapy at the occurrence of fever results in low mortality, but does not allow assignment of cases to different categories. PMID- 8495084 TI - Nordic children with myelomeningocele. Parents' assessments of the handicap and physicians' classifications of the disabilities. AB - The differences between parents' assessments of their child's handicap and professionals' assessment of disabilities were studied in 486 Nordic children with myelomeningocele aged 4-18 years. Although disability and handicap are conceptually different, agreement between the parents' assessments of the handicap and the degree of disability according to Lorber's classification was found in 51% of cases. The parents' assessments showed close agreement with overall disability according to Lagergren's method in 45% of cases. The factors most strongly associated with parental assessment of the handicap were the child's motor disability, intellectual functioning, faecal and urinary incontinence and the parents' inclination to feel inadequate with respect to the child's needs. Data from professional assessment of disabilities alone are of limited value in understanding the impact of disabilities on the daily life of a child. PMID- 8495085 TI - The position of the tongue during rooting reflexes elicited in newborn infants before the first suckle. AB - A common breast-feeding problem is when the infant "places its tongue in its palate" and has difficulties in attaching to its mother's nipple. The aim of this study was to document the position of the tongue in the mouth cavity during rooting reflexes elicited in newborn infants before the first suckle. Eleven healthy, full-term infants were videotaped 101 +/- 31 min after birth during an evoked distinct rooting reflex before the first suckle. The videotaped rooting reflex was analyzed in detail concerning the degree of turning of the head, mouth opening and position of the tongue, in pictures that were "frozen" at specific intervals. "Licking movements" preceded and followed the rooting reflex in the alert infants. In 10 of the 11 infants the tongue was placed in the bottom of the mouth cavity during a distinct rooting reflex (p = < 0.05). It is suggested that forcing the infant to the breast might abolish the rooting reflex and disturb placement of the tongue. A healthy infant should have the opportunity of showing hunger and optimal reflexes, and attach to its mother's nipple by itself. PMID- 8495086 TI - Urinary nitrite excretion in premature infants: effects of transfusion or indomethacin. AB - Urinary nitrite excretion, an index of L-arginine-dependent nitric oxide formation, was quantified daily for two weeks, in very low-birth-weight (< 1500 g) premature infants. A transient 52% reduction in nitrite excretion was noted on the day of transfusions (54 +/- 10 versus 26 +/- 6 mumol/mmol creatinine, before and during transfusion, respectively, n = 24, p < 0.02). Indomethacin administration in six infants was associated with a dramatic increase in nitrite excretion from a basal median value of 3 to 76 mumol/mmol creatinine (p < 0.05). Nitrite excretion returned to baseline on day 3 after indomethacin administration. In two infants who received indomethacin and transfusions on the same day, the stimulatory effect on nitrite excretion by indomethacin overwhelmed any depressive effect of transfusions. These results suggest that L-arginine utilization is influenced by common therapeutic strategies in these high-risk infants. PMID- 8495087 TI - Small intestinal biopsy in children with coeliac disease: measurement of radiation dose and analysis of risk. AB - To verify the diagnosis of coeliac disease in childhood, three consecutive small intestinal biopsies are performed under fluoroscopic control. To assess the amount of radiation dose absorbed during biopsy, dose measurements were performed both in patients and in a phantom model. These measurements were used for a theoretical assessment of cancer risk and shortening of life due to radiation exposure. The cancer excess lifetime mortality risk (CELMR) was 0.001, i.e. 1 case per 1000 children with a diagnosis of coeliac disease. The loss of life expectancy after three small intestinal biopsies in childhood was approximately 15% of the risk due to lifetime exposure to natural background radiation. These results should be compared with the reported increased risk of malignancy for undiagnosed coeliac disease in adult age. Although the excess risk of the biopsies was small, all efforts should be made to use a technique and equipment giving the least radiation dose. PMID- 8495088 TI - Plasma endothelin-1 concentrations at different ages during infancy and childhood. PMID- 8495089 TI - Height and body mass index of seven-year-old Stockholm schoolchildren from 1940 to 1990. PMID- 8495090 TI - Nephrolithiasis in cystic fibrosis. PMID- 8495091 TI - Early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. PMID- 8495092 TI - Plasma concentration of islet amyloid polypeptide in healthy children and patients with insulin-dependent diabetes mellitus. PMID- 8495093 TI - Unusual presentation of the immotile cilia syndrome in two children. PMID- 8495094 TI - Comment on antigen-reduced infant formulae. ESPGAN Committee on Nutrition. PMID- 8495095 TI - Opsoclonus polymyoclonia syndrome. PMID- 8495096 TI - Herpes simplex hepatitis with chronic cholestasis in a newborn. AB - In the case of the central nervous system or hepatic involvement, the prognosis of neonatal herpes simplex infection remains poor, despite antiviral drugs, presumably effective if given early. We report the case of a neonate with herpes simplex hepatitis, where the course of the illness was unusual with chronic, ultimately fatal, cholestasis. The treatment was not effective, because its administration was delayed, because of high infant C reactive protein level and the absence of clinical maternal genital infection, and because it was interrupted due to misleading information: clinical improvement, negative viral tests and raised herpes IgG antibody titer. PMID- 8495097 TI - Successful trimethoprim-sulfamethoxazole therapy in a patient with hyperimmunoglobulin E syndrome. AB - A male patient with hyperimmunoglobulin E syndrome is described. Recurrent lymphadenitis and cutaneous staphylococcal abscesses were resistant to various antibiotics, and chemotaxis and hydrogen peroxide production of polymorphonuclear leukocytes were impaired. Following trimethoprim-sulfamethoxazole therapy, he was free from the above infections, and impaired polymorphonuclear leukocyte functions recovered and serum IgE decreased to approximately one-fifth of its initial level. Subsequent irregular medications, however, resulted in impairment of polymorphonuclear leukocyte functions and an increased serum IgE concentration, which recovered after regular resumption of trimethoprim sulfamethoxazole treatment. From these results, the beneficial effects of trimethoprim-sulfamethoxazole in hyperimmunoglobulin E syndrome are clinically apparent, but in vitro studies failed to demonstrate the positive effect of trimethoprim-sulfamethoxazole on polymorphonuclear leukocytes and their mechanism still remains to be elucidated. PMID- 8495098 TI - Acute lymphoblastic leukemia following optic glioma treated by radiotherapy and surgery. AB - A 14-year-old girl was diagnosed as having acute lymphoblastic leukemia following 5000 cGy cranial radiotherapy for treatment of optic glioma. In the absence of underlying predisposing factors, development of acute leukemia was attributed to the oncogenic effect of radiation. PMID- 8495099 TI - Trichorhinophalangeal syndrome, type I, with avascular necrosis of the femoral head. AB - We report the case of a seven-year-old girl with peculiar facial traits who presented for right coxalgia of six weeks' duration. The phenotypic findings corresponded to a trichorhinophalangeal syndrome, type I, and the clinical, radiological and gammagraphic characteristics were indicative of avascular necrosis of the right femoral head, Legg-Perthes-Calve disease. PMID- 8495100 TI - Some thoughts about theoretical frameworks in historical research. PMID- 8495101 TI - The midwives Shifra and Puah: biblical heroines. PMID- 8495102 TI - Historic nursing exhibit held at the 1992 international nursing research conference. PMID- 8495103 TI - Oligonucleotide therapeutics: a prospectus. PMID- 8495104 TI - Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120. AB - Although having variability in primary sequence, the v3 loop of gp120 in pathogenic strains of human immunodeficiency virus type-1 (HIV-1) is positively charged and known to interact with sulfated polysaccharides. Because the interaction of sulfated polysaccharides with the v3 loop inhibits HIV infection in vitro, we investigated the interaction of the v3 loop with phosphodiester (PO) and phosphorothioate (PS) oligodeoxynucleotides (oligos). In a solid-phase ELISA assay, a PS 28-mer homopolymer of cytidine, SdC28, blocked the binding of the v3 loop-specific monoclonal antibody (mAb) 9284 to rgp120 more potently than did dextran sulfate. In addition, like dextran sulfate, SdC28 appeared to bind specifically to the v3 loop, because neither compound inhibited the binding of other anti-gp120 mAbs. In contrast to PS oligos, PO oligos did not inhibit mAb 9284 binding. The length dependence of the interaction of PS oligos with the v3 loop was studied by using a series of PS oligos. A discrete loss of inhibiting activity occurred as a function of decreasing PS oligo length, which was most marked between PS oligos of 18-mer and 12-mer in length. We further probed the chemical nature of the interaction of oligos with gp120 by measuring the gp120 binding affinities of PS and PO oligos of various lengths. We employed a 5'-32P labeled alkylating oligo, ClRNH32P-OdT15, and determined that the Km of gp120 binding is 4 microM. We also determined values of competition constant (Kc) for PS competitors of ClRNH32P-OdT15 binding. The binding constant (= 1/Kc) for PS oligos showed a discrete increase in gp120 binding for PS oligos > 12- to 18-mer in length, with no further increment beyond an 18-mer. Given the important role of the v3 loop in HIV-1 pathogenicity, these data suggest that therapeutic trials of PS oligos should be considered. PMID- 8495105 TI - Computer-aided search for effective antisense RNA target sequences of the human immunodeficiency virus type 1. AB - For the biological and therapeutic application of antisense nucleic acids, there is a need to identify effective local target regions of given cellular target mRNAs or viral single-stranded nucleic acids. One critical parameter for the effectiveness of antisense nucleic acids could be the potential of intramolecular folding of a given sequence element of the target strand and the antisense strand, respectively. The folding potential of such subsequences was calculated by using an established secondary structure prediction algorithm. For the genomic RNA and the complementary RNA strand of the human immunodeficiency virus type 1 (HIV-1), an energy profile was calculated that monitors the local folding potential of each sequence position surrounded by a window of given length ranging from 50 to 400 nucleotides. The resulting energy profile was compared to the effectiveness of HIV-1-directed antisense RNAs. It was found that significant minima of the local folding potential (high delta G values) correlated with antisense RNA target regions involved in strong inhibition of HIV-1 replication that had been measured independently in two earlier studies by using different experimental approaches. Conversely, antisense RNAs directed against local subregions with a high folding potential (low delta G values) showed weak or no antiviral effect in human cells. The results indicate that analyses of the local folding potential of a given target RNA can support the selection of effective target sequences for antisense RNA. PMID- 8495106 TI - Comparison of cellular binding and uptake of antisense phosphodiester, phosphorothioate, and mixed phosphorothioate and methylphosphonate oligonucleotides. AB - The effects of phosphorothioate (S-oligonucleotide) or terminal phosphorothioate phosphodiester (S-O-oligonucleotides) or methylphosphonate-phosphodiester (MP-O oligonucleotides) modifications on mouse spleen cell surface binding, uptake, and degradation were studied using fluorescein (FITC)-conjugated oligonucleotides. S oligonucleotides had the highest cell binding and uptake, followed by S-O-, O-, and MP-O-oligonucleotides. Competition studies indicated that S-oligonucleotides have an increased affinity for cell membrane oligonucleotide binding sites, because they could completely block O-oligonucleotide binding at a molar ratio of just 0.1. Uptake of all oligonucleotides was higher in B cells than T cells and was increased by stimulation with the B-cell mitogen, lipopolysaccharide. Although our cells had been purified using conventional techniques to eliminate dead cells, there remained about 5% of cells that were dead or dying, as determined by flow cytometry using propidium iodide staining. Of note, oligonucleotide association with dead cells was approximately 50-fold greater than that with living cells. Confocal microscopy confirmed that the oligonucleotides in living cells were intracellular, and indicated little nuclear uptake by 4 h. While extensive degradation of intracellular O-oligonucleotides was apparent by 4 h, there was no detectable degradation of S-, S-O, or MP-O oligonucleotides. PMID- 8495107 TI - Effects of sequence of thioated oligonucleotides on cultured human mammary epithelial cells. AB - We have compared the effects of a number of different oligonucleotides on the growth and morphology of normal finite life span and immortally transformed human mammary epithelial cells. The oligonucleotide sequences chosen initially for study were based on that of the NB-1 gene, which encodes a calmodulin-like protein of unknown function. We found that certain thioated oligonucleotides 15 20 residues in length altered the morphology and decreased the growth rate of the normal cells in a concentration-dependent manner. These effects were rapid, occurring within 24-48 h of oligonucleotide addition. The effects, which occurred without an accompanying detectable decrease in the levels of NB-1 mRNA or protein, were most pronounced in the normal epithelial cells, less apparent in the immortalized epithelial cells, and unobserved in normal breast fibroblasts. Identical sequences having mixed phosphodiester and phosphorothioate backbones, or phosphodiester backbones alone, had little or no effect on normal epithelial cell morphology or growth. Two out of seven additional thioated oligonucleotides which were not complementary to NB-1 mRNA, also affected normal epithelial cell morphology and growth when used at similar concentrations (10 microM). Taken together, the observed effects on normal epithelial cells indicate that certain thioated oligonucleotides may have pharmacological consequences that do not depend on strict complementarity of their sequences to known mRNAs. PMID- 8495109 TI - An indexed bibliography of antisense literature, 1992. PMID- 8495108 TI - Ribozymes: use as anti-HIV therapeutic molecules. PMID- 8495110 TI - Hypercholesterolemia. Is the fat still in the fire? PMID- 8495111 TI - Double standards in patient screening? PMID- 8495112 TI - Hypodermoclysis and system management. PMID- 8495113 TI - Sexual assault. Effects of the research process on all the participants. PMID- 8495114 TI - Radiology rounds. Anterior shoulder dislocation. PMID- 8495115 TI - Dermacase. Seborrheic keratosis. PMID- 8495116 TI - The reluctant resident. PMID- 8495117 TI - Who goes to after-hours clinics? Demographic analysis of an after-hours clinic. AB - This study examines an after-hours clinic developed by family physicians of a major community hospital. The physicians have notable linkages with the hospital, and most of the patients come from the practices of the physicians on staff. Hospital-linked clinics of this type could have an increasingly important role as mechanisms of health care delivery continue to evolve. PMID- 8495118 TI - Performance of the "house doctor". Effect of physician-to-patient ratio on follow up in long-term care facilities. AB - Do physicians with many patients in a long-term care facility provide more timely follow up of their drug orders than those with only a few? We reviewed 60 charts at random in three intermediate care facilities. Physician practices fell into two distinct groups. Those with more than 17 patients followed up sooner than those with fewer than six. We recommend a "house doctor" model of care for patients whose follow up is poor. PMID- 8495119 TI - Dissemination of guidelines on cholesterol. Effect on patterns of practice of general practitioners and family physicians in Ontario. Ontario Task Force on the Use and Provision of Medical Services. AB - A telephone survey of a random sample of Ontario family physicians was conducted 6 to 8 months after disseminating evidence-based guidelines for screening and managing asymptomatic hypercholesterolemia. Seventy-eight percent of respondents stated they followed these guidelines. However, specific questions revealed as few as 5% of respondents actually followed the guidelines. PMID- 8495120 TI - Control of anticoagulant and antiplatelet therapy. Managing patients with acute thrombotic disorders. AB - Indications for using standard anticoagulants, heparin and warfarin; the dosage and route of administration; the importance of monitoring therapy with reliable laboratory indices; and complications of therapy are discussed. Acetylsalicylic acid and ticlopidine can be used as antiplatelet agents. Because their effect on platelet function is not monitored clinically, their clinical indications are emphasized. PMID- 8495121 TI - Cardiovascular risk factors in perspective. AB - Coronary heart disease and other manifestations of atherosclerosis are leading causes of morbidity and mortality in Canada. Despite favourable trends in recent years, we should try to reduce cardiovascular events further. Physicians must translate current knowledge into public health policies and management strategems for individual patients. Patients are best served by a comprehensive risk management approach, involving nonpharmacological (mainly lifestyle) changes and drug therapy. PMID- 8495122 TI - Coronary artery bypass surgery. Which patients benefit? AB - Thousands of coronary bypass operations are performed in Canada each year. Some result in longer life or improved quality of life by reducing angina, but others do not. Where the potential benefit is unknown, physicians must consider the patient's work, home life, and personality. Clinical intuition is still needed to determine which patients will benefit. PMID- 8495123 TI - Reoperation after coronary bypass grafting. AB - Coronary artery bypass grafting is one of the most commonly performed surgical procedures in the western world, and myocardial revascularization during the first operation is well established. But patients are now surviving beyond the patency of their primary grafts. Repeat myocardial revascularization can be performed successfully in patients who have adequate ventricular function and graftable distal vessels. PMID- 8495124 TI - Chronic fatigue syndrome. A fresh look at an old problem. AB - Chronic fatigue syndrome (CFS), an organic disease of unexplained origin, affects about three people in 100,000. Symptoms last approximately 2 1/2 years, and most CFS patients return to normal health. Diagnosis of CFS is by exclusion. No single remedy has yet proven consistently beneficial. Family physicians can help by providing medical validation of disability to persons who might otherwise be seen as malingerers. PMID- 8495125 TI - Photodamaged skin. Update on therapeutic management. AB - With baby boomers aging, the medical community is ushered into a new era of patient care, that of cosmetic maintenance and rejuvenation. The authors critically review pharmacologic treatments for preventing and treating photodamaged skin. Issues concerning sunscreens, tretinoin, silicone tissue augmentation, fat transplantation, collagen replacement therapy, and chemical exfoliation of the skin are addressed. PMID- 8495126 TI - [Supervision of family medicine residents. Competences and qualities]. AB - Clinical supervision activities are an important part of the education of future family physicians. In this article, the author describes clinical skills, teaching skills, and personal qualities that family physician-supervisors should acquire during their professional training. PMID- 8495127 TI - Decongestant-induced hypertensive crisis. PMID- 8495128 TI - [Topical antiseptics]. PMID- 8495129 TI - Quo vadis: Part 3. PMID- 8495130 TI - Gestational diabetes mellitus. PMID- 8495131 TI - Similar drug names cause concern. PMID- 8495132 TI - Instead of some other medical specialty. Tulk balances art and medicine. PMID- 8495133 TI - Radiology rounds. Testicular neoplasm. PMID- 8495134 TI - Dermacase. Erythema nodosum. PMID- 8495135 TI - Cognitive function. Survey of elderly persons living at home in rural Newfoundland. AB - We tested the cognitive function of elderly, community-dwelling residents in rural Newfoundland using the Canadian Mental Status Questionnaire. The prevalence of moderate and severe cognitive impairment was 9.3%. Physicians in the community had recognized those with severe impairment, but had not recognized any of those with moderate impairment. Cognitive function testing should be part of the periodic health examination of older patients. PMID- 8495136 TI - Childbirth in the north. A qualitative study in the Moose Factory zone. AB - Cree women from the Moose Factory zone were asked about their views on evacuation for childbirth. Significant concerns cited were separation from children, loneliness, boredom, and the hospital accommodations. Shopping, the medical staff and equipment, and the opportunity to visit relatives were considered positive factors. Suggested improvements were to bring along family members, to provide alternative accommodation, and to have activities to occupy the time. PMID- 8495137 TI - Asthma. Assessment and management in a pediatric hospital. AB - To evaluate the method used to assess and subsequently manage children with asthma, a retrospective chart review was carried out at the Children's Hospital of Western Ontario in London. Charts of 78 children diagnosed with asthma were randomly selected from emergency room daily records and inpatient files. Pharmacologic management of acute asthma proved adequate, but children with daily asthma symptoms likely would not have been identified or treated. PMID- 8495138 TI - Detecting and managing gestational diabetes. AB - Gestational diabetes is an asymptomatic metabolic disorder of pregnancy associated with increased morbidity in mother and fetus. Early detection and intervention improve pregnancy outcome. This article reviews the current approach to diagnosis and management. Specific guidelines for nutritional management and insulin use are included. PMID- 8495139 TI - How safe are safes? Efficacy and effectiveness of condoms in preventing STDs. AB - Condoms are widely promoted for preventing sexually transmitted diseases, with an implicit message that a properly used condom will ensure that you are safe from STDs. A literature review shows that little solid evidence supports this belief. PMID- 8495140 TI - Rear-end accident victims. Importance of understanding the accident. AB - Family physicians regularly treat victims of rear-end vehicle accidents. This article describes how taking a detailed history of the accident and understanding the significance of the physical events is helpful in understanding and anticipating patients' morbidity and clinical course. Eight questions to ask patients are suggested to help physicians understand the severity of injury. PMID- 8495141 TI - Relationship management and the borderline patient. AB - Treating a patient with borderline personality disorder is fraught with peril. Some psychotherapies and medications seem to make matters worse, yet these very patients are some of the most persistent in demanding help. This happens because the context of treatment, the traditional physician-patient social contract, and the personal and professional impulses of the physician can actually feed and reinforce the patient's pathological behaviour. Relationship management offers a way to understand the problem and to handle it. PMID- 8495142 TI - Managing resistant depression. When patients do not respond to therapy. AB - Many factors can influence outcome in the management of depressive illness, a major public health problem with significant associated mortality and morbidity. Two-thirds of patients will respond to antidepressants. The remainder can be treated in other ways. Only about 7% of patients are absolutely treatment resistant, and even they can be helped. PMID- 8495143 TI - [Screening of language disorders in the preschool period]. AB - Between five and 20% of preschool age children have language problems. These can be related to the child's hearing, socioeconomic status, intellectual development, or a psychiatric disorder. Even when it is difficult to recommend a formal screening program, family physicians can interpret delays in speech and language as "indicators" of underlying disorders. PMID- 8495144 TI - Pain relief for headaches. Is self-medication a problem? AB - Recent survey results show that 3.2 million Canadians suffer from migraine attacks. Among those responding to the survey, 36% were currently consulting physicians for their headaches, 45% had discontinued consulting physicians, and 19% had never sought medical help. About 90% of these migraine sufferers used over-the-counter drugs. Risks associated with improper use of OTC medications include addiction, gastric irritation, liver toxicity, and rebound headache syndrome. PMID- 8495145 TI - Nocturnal enuresis. Treatment options. AB - Bed-wetting is a common and disturbing problem for children and their families. Underlying causes are rarely found and should be suspected from the history rather than from investigations. Children older than 7 years can usually be cured if they are motivated enough to use an alarm conditioning device. Intranasal desmopressin acetate, the current drug of choice, will produce only temporary relief. PMID- 8495146 TI - Patients with macroscopic hematuria. Importance of examining multiple urine specimens. PMID- 8495147 TI - Generalism. PMID- 8495148 TI - Chickenpox during pregnancy. PMID- 8495149 TI - Restorative gardens. PMID- 8495150 TI - A role for medical angiologists? PMID- 8495151 TI - Mental health problems at work. PMID- 8495152 TI - "Self referral": a potential conflict of interest. PMID- 8495153 TI - Does cimetidine cause weight loss? PMID- 8495154 TI - Modified paediatric resuscitation chart. AB - OBJECTIVES: To determine whether a modified paediatric resuscitation reference chart improves the speed and accuracy of calculation of doses of drugs in simulated paediatric cardiopulmonary arrests when compared with the chart devised by Oakley. DESIGN: A prospective study in which a series of randomly assigned questions was used to compare the performance of doctors using the two charts. SETTING: Accident and emergency departments in two hospitals. SUBJECTS: 31 senior house officers. MAIN OUTCOME MEASURES: The speed and accuracy of calculation of volumes of drugs to be administered. RESULTS: The modified chart significantly increased the accuracy of the calculations (62/62 v 43/62, p < 0.01 [corrected]), the speed of correct calculations (6.8 v 36.0 s, p < 0.0001), and the number of calculations that were completed (62/62 v 50/62, p < 0.001). CONCLUSIONS: The modified paediatric resuscitation chart should supersede the existing chart. PMID- 8495155 TI - Treatment of acute mountain sickness by simulated descent: a randomised controlled trial. AB - OBJECTIVE: To evaluate the therapeutic efficacy of a portable hyperbaric chamber for treatment of acute mountain sickness. DESIGN: Controlled randomised trial over two mountaineering seasons. SETTING: High altitude research laboratory at 4559 m above sea level. SUBJECTS: 64 climbers with acute mountain sickness randomly allocated to different treatments. INTERVENTIONS: One hour of treatment in the hyperbaric chamber at a pressure of 193 mbar or 20 mbar as control or bed rest. MAIN OUTCOME MEASURES: Symptoms of acute mountain sickness before, immediately after, and 12 hours after treatment. Permitted intake of analgesic and antiemetic drugs in the follow up period. RESULTS: Treatment with 193 mbar caused greater relief of symptoms than did control treatment or bed rest. During the 12 hour follow up period intake of analgesics was similar (58-80% of subjects in each group). Symptom scores had improved in all subjects after 12 hours with no significant differences between groups. CONCLUSIONS: One hour of treatment with 193 mbar in a portable hyperbaric chamber, corresponding to a descent of 2250 m, leads to a short term improvement in symptoms of acute mountain sickness but has no beneficial long term effects attributable to pressurisation. PMID- 8495156 TI - Relationship between adult victims of assault and children at risk of abuse. PMID- 8495157 TI - Decision making by general practitioners in diagnosis and management of lower urinary tract symptoms in women. AB - OBJECTIVE: To identify factors influencing decision making by general practitioners in the diagnosis and treatment of lower urinary tract symptoms in women. SETTING: Two suburban London general practices. SUBJECTS: Women presenting to their family doctor with lower urinary tract symptoms. DESIGN: After each consultation the doctor completed a questionnaire on presenting symptoms; clinical examination; investigations undertaken; presence of psychological, social, and menstrual problems; patients' requests for antibiotics; antibiotic prescribing; knowledge of the patient; attitude towards the consultation; and any other factors assisting in diagnosis and management. Finally, doctors predicted the presence or absence of clinically important bacteriuria. Each woman completed a demographic questionnaire, the 12 item general health questionnaire, and the modified menstrual distress questionnaire, after which each provided a clean catch midstream urine sample. Case notes were examined for information on previous reports of results of urine analysis. RESULTS: When the general practitioners did not know the patients well they were 4.5 times more likely to assume that there was a clinically important infection. When they knew the patient well, they were four times more likely to make a correct prediction of the test result and 12 times less likely to prescribe antibiotics. Doctors were five times more likely to predict the test result correctly in patients from social classes 1 and 2 and were six times more likely to prescribe antibiotics for the older women in the sample. CONCLUSIONS: In women presenting with urinary tract symptoms, these family practitioners seemed to take no particular regard of physical, psychological, or menstrual factors in making their assessments. They were most accurate in their prediction of the result of urine analysis and least likely to prescribe antibiotics when they had a good general knowledge of the patient. Which came first, the diagnosis or prescribing, is difficult to say and probably differed in individual cases. Doctors tended to be more conservative in their management of older women and those whom they knew less well. PMID- 8495158 TI - Why is the outcome of transient ischaemic attacks different in different groups of patients? AB - The outcomes of each of three large cohorts of patients with transient ischaemic attacks, which were studied in the same country at much the same time with the same methods, were compared and found to be quite different from each other. The differences in outcome were related not only to different strategies of treatment but also to differences in the prevalence and level of important prognostic factors (for example, case mix) and other factors such a the time delay from transient ischaemic attack to entry into the study and the play of chance. The implications for purchasers of health care are that they cannot rely solely on non-randomised comparisons of outcome of patients treated in competing units as a measure of the quality of care (which has only rather modest effects) without accounting for other factors that may influence outcome such as the nature of the illness, the case mix, observer bias, and the play of chance. PMID- 8495159 TI - Inappropriate publication of trial results and potential for allegations of illegal share dealing. AB - There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any sponsoring organisations. PMID- 8495160 TI - Gall stones: the real issues. PMID- 8495161 TI - Helping people with dementia feel at home. PMID- 8495162 TI - ABC of sleep disorders. Non-Psychotropic drugs and sleep. PMID- 8495163 TI - Diabetic care in general practice. PMID- 8495164 TI - Primary prevention of neural tube defects with folic acid. PMID- 8495165 TI - Primary prevention of neural tube defects with folic acid. PMID- 8495166 TI - Designer hips. PMID- 8495167 TI - Effective and acceptable treatment for depression. PMID- 8495168 TI - Effective and acceptable treatment for depression. PMID- 8495169 TI - Effective and acceptable treatment for depression. PMID- 8495170 TI - Effective and acceptable treatment for depression. PMID- 8495171 TI - Effective and acceptable treatment for depression. PMID- 8495172 TI - Effective and acceptable treatment for depression. PMID- 8495173 TI - Fluoridation of drinking water. PMID- 8495174 TI - Fluoridation of drinking water. PMID- 8495175 TI - Unpublished data in drug advertisements. PMID- 8495176 TI - Unpublished data in drug advertisements. PMID- 8495177 TI - Women's perception of obstetric and gynecological examinations. PMID- 8495178 TI - Heart disease screening in Japanese children. PMID- 8495179 TI - Early infertility treatments derived from human pituitary. PMID- 8495180 TI - Parental irradiation and excess childhood leukemia. PMID- 8495181 TI - Screening for prostatic cancer. PMID- 8495182 TI - Infant mortality in Switzerland. PMID- 8495183 TI - Medical details crucial for residential care. PMID- 8495184 TI - Vaccines should be more environmentally stable. PMID- 8495185 TI - Trauma and mental health of children in Gaza. PMID- 8495186 TI - Freezing assets to pay for long-term care. PMID- 8495187 TI - Mycobacteria in Crohn's disease. PMID- 8495188 TI - Asthma management guidelines. PMID- 8495189 TI - Asthma management guidelines. PMID- 8495190 TI - Asthma management guidelines. PMID- 8495191 TI - Asthma management guidelines. PMID- 8495192 TI - The curious case of protein splicing: mechanistic insights suggested by protein semisynthesis. AB - The gradual accumulation of examples of protein splicing, in which a nested intervening sequence is spliced out of the interior of a polyprotein precursor, suggests that this curious phenomenon might prove to have universal phylogenetic distribution and biological significance. The known examples are reviewed, with the aim of establishing underlying patterns, and a generalized mechanism of autocatalytic protein splicing is proposed. The testable consequences of such a proposal and the possible evolutionary origins of the phenomenon are discussed. PMID- 8495193 TI - Covalent binding properties of the human complement protein C4 and hydrolysis rate of the internal thioester upon activation. AB - The complement proteins C3 and C4 have an internal thioester. Upon activation on the surface of a target cell, the thioester becomes exposed and reactive to surface-bound amino and hydroxyl groups, thus allowing covalent deposition of C3 and C4 on these targets. The two human C4 isotypes, C4A and C4B, which differ by only four amino acids, have different binding specificities. C4A binds more efficiently than C4B to amino groups, and C4B is more effective than C4A in binding to hydroxyl groups. By site-directed mutagenesis, the four residues in a cDNA clone of C4B were modified. The variants were expressed and their binding properties studied. Variants with a histidine residue at position 1106 showed C4B like binding properties, and those with aspartic acid, alanine, or asparagine at the same position were C4A-like. These results suggest that the histidine is important in catalyzing the reaction of the thioester with water and other hydroxyl group-containing compounds. When substituted with other amino acids, this reaction is not catalyzed and the thioester becomes apparently more reactive with amino groups. This interpretation also predicts that the stability of the thioester in C4A and C4B, upon activation, will be different. We measured the time course of activation and binding of glycine to C4A and C4B. The lag in the binding curve behind the activation curve for C4A is significantly greater than that for C4B. The hydrolysis rates (k0) of the thioester in the activated proteins were estimated to be 0.068 s-1 (t1/2 of 10.3 s) for C4A and 1.08 s-1 (t1/2 of 0.64 s) for C4B. These results indicate that the difference in hydrolysis rate of the thioester accounts, at least in part, for the difference in the binding properties of C4A and C4B. PMID- 8495195 TI - Chymotrypsin inhibitory activity of normal C1-inhibitor and a P1 Arg to His mutant: evidence for the presence of overlapping reactive centers. AB - C1-inhibitor is a serine proteinase inhibitor that is active against C1s, C1r, kallikrein, and factor XII. Recently, it has been shown that it also has inhibitory activity against chymotrypsin. We have investigated this activity of normal human C1-inhibitor, normal rabbit C1-inhibitor, and P1 Arg to His mutant human C1-inhibitors and find that all are able to inhibit chymotrypsin and form stable sodium dodecyl sulfate-resistant complexes. The Kass values show that the P1 His mutant is a slightly better inhibitor of chymotrypsin than normal human C1 inhibitor (3.4 x 10(4) compared with 7.3 x 10(3)). The carboxy-terminal peptide of normal human C1-inhibitor, derived from the dissociated protease-inhibitor complex, shows cleavage between the P2 and P1 residues. Therefore, as with alpha 2-antiplasmin, C1-inhibitor possesses two overlapping P1 residues, one for chymotrypsin and the other for Arg-specific proteinases. In contrast, with the P1 His mutant, the peptide generated from the dissociation of its complex with chymotrypsin demonstrated cleavage between the P1 and P'1 residues. Therefore, unlike alpha 2-antiplasmin, chymotrypsin utilizes the P2 residue as its reactive site in normal C1-inhibitor but utilizes the P1 residue as its reactive site in the P1 His mutant protein. This suggests that the reactive center loop allows a degree of induced fit and therefore must be relatively flexible. PMID- 8495194 TI - Redox properties of protein disulfide isomerase (DsbA) from Escherichia coli. AB - The redox properties of periplasmic protein disulfide isomerase (DsbA) from Escherichia coli were analyzed by measuring the equilibrium constant of the oxidation of reduced DsbA by oxidized glutathione. The experiments are based on the finding that the intrinsic tryptophan fluorescence of DsbA increases about threefold upon reduction of the enzyme, which can be explained by the catalytic disulfide bridge quenching the fluorescence of a neighboring tryptophan residue. From the specific fluorescence of DsbA equilibrated in the presence of different ratios of reduced and oxidized glutathione at pH 7, an equilibrium constant of 1.2 x 10(-4) M was determined, corresponding to a standard redox potential (E'0) of DsbA of -0.089 V. Thus, DsbA is a significantly stronger oxidant than cytoplasmic thioredoxins and its redox properties are similar to those of eukaryotic protein disulfide isomerase. The equilibrium constants for the DsbA/glutathione equilibrium were found to be strongly dependent on pH and varied from 2.5 x 10(-3) M to 3.9 x 10(-5) M between pH 4 and 8.5. The redox state dependent fluorescence properties of DsbA should allow detailed physicochemical studies of the enzyme as well as the quantitative determination of the oxidized protein by fluorescence titration with dithiothreitol and open the possibility to observe bacterial protein disulfide isomerase "at work" during catalysis of oxidative protein folding. PMID- 8495196 TI - Estimation of the maximum change in stability of globular proteins upon mutation of a hydrophobic residue to another of smaller size. AB - Although the hydrophobic effect is generally considered to be one of the most important forces in stabilizing the folded structure of a globular protein molecule, there is a lack of consensus on the precise magnitude of this effect. The magnitude of the hydrophobic effect is most directly measured by observing the change in stability of a protein molecule when an internal hydrophobic residue is mutated to another of smaller size. Results of such measurements have, however, been confusing because they vary greatly and are generally considerably larger than expected from the transfer free energies of corresponding small molecules. In this article, a thermodynamic argument is presented to show (1) that the variation is mainly due to that in the flexibility of the protein molecule at the site of mutation, (2) that the maximum destabilization occurs when the protein at the site of mutation is rigid, in which case the value of the destabilization is approximately given by the work of cavity formation in water, and (3) that the transfer free energy approximately gives the minimum of the range of variations. The best numerical agreements between the small molecule and the protein systems are obtained when the data from the small molecule system are expressed as the molarity-based standard free energies without other corrections. PMID- 8495197 TI - Crystal structure analysis of amicyanin and apoamicyanin from Paracoccus denitrificans at 2.0 A and 1.8 A resolution. AB - The crystal structure of amicyanin, a cupredoxin isolated from Paracoccus denitrificans, has been determined by molecular replacement. The structure has been refined at 2.0 A resolution using energy-restrained least-squares procedures to a crystallographic residual of 15.7%. The copper-free protein, apoamicyanin, has also been refined to 1.8 A resolution with residual 15.5%. The protein is found to have a beta-sandwich topology with nine beta-strands forming two mixed beta-sheets. The secondary structure is very similar to that observed in the other classes of cupredoxins, such as plastocyanin and azurin. Amicyanin has approximately 20 residues at the N-terminus that have no equivalents in the other proteins; a portion of these residues forms the first beta-strand of the structure. The copper atom is located in a pocket between the beta-sheets and is found to have four coordinating ligands: two histidine nitrogens, one cysteine sulfur, and, at a longer distance, one methionine sulfur. The geometry of the copper coordination is very similar to that in the plant plastocyanins. Three of the four copper ligands are located in the loop between beta-strands eight and nine. This loop is shorter than that in the other cupredoxins, having only two residues each between the cysteine and histidine and the histidine and methionine ligands. The amicyanin and apoamicyanin structures are very similar; in particular, there is little difference in the positions of the coordinating ligands with or without copper. One of the copper ligands, a histidine, lies close to the protein surface and is surrounded on that surface by seven hydrophobic residues. This hydrophobic patch is thought to be important as an electron transfer site. PMID- 8495198 TI - Reduced representation model of protein structure prediction: statistical potential and genetic algorithms. AB - A reduced representation model, which has been described in previous reports, was used to predict the folded structures of proteins from their primary sequences and random starting conformations. The molecular structure of each protein has been reduced to its backbone atoms (with ideal fixed bond lengths and valence angles) and each side chain approximated by a single virtual united-atom. The coordinate variables were the backbone dihedral angles phi and psi. A statistical potential function, which included local and nonlocal interactions and was computed from known protein structures, was used in the structure minimization. A novel approach, employing the concepts of genetic algorithms, has been developed to simultaneously optimize a population of conformations. With the information of primary sequence and the radius of gyration of the crystal structure only, and starting from randomly generated initial conformations, I have been able to fold melittin, a protein of 26 residues, with high computational convergence. The computed structures have a root mean square error of 1.66 A (distance matrix error = 0.99 A) on average to the crystal structure. Similar results for avian pancreatic polypeptide inhibitor, a protein of 36 residues, are obtained. Application of the method to apamin, an 18-residue polypeptide with two disulfide bonds, shows that it folds apamin to native-like conformations with the correct disulfide bonds formed. PMID- 8495199 TI - Binding of amino acid side chains to preformed cavities: interaction of serine proteinases with turkey ovomucoid third domains with coded and noncoded P1 residues. AB - In the association of serine proteinases with their cognate substrates and inhibitors an important interaction is the fitting of the P1 side chain of the substrate or inhibitor into a preformed cavity of the enzyme called the S1 pocket. In turkey ovomucoid third domain, which is a canonical protein proteinase inhibitor, the P1 residue is Leu18. Here we report the values of equilibrium constants, Ka, for turkey ovomucoid third domain and 13 additional Leu18X variants with six serine proteinases: bovine alpha chymotrypsin A, porcine pancreatic elastase, subtilisin Carlsberg, Streptomyces griseus proteinases A and B, and human leukocyte elastase. Eight of the Xs are coded amino acids: Ala, Ser, Val, Met, Gln, Glu, Lys, and Phe, and five are noncoded: Abu, Ape, Ahx, Ahp, and Hse. They were chosen to simplify the interamino acid comparisons. In the homologous series of straight-chain side chains Ala, Abu, Ape, Ahx, Ahp, free energy of binding decreases monotonically with the side-chain length for chymotrypsin with large binding pocket, but even for this enzyme shows curvature. For the two S. griseus enzymes a minimum appears to be reached at Ahp. A minimum is clearly evident for the two elastases, where increasing the side-chain length from Ahx to Ahp greatly weakens binding, but much more so for the apparently more rigid pancreatic enzyme than for the more flexible leukocyte enzyme. beta Branching (Ape/Val) is very deleterious for five of the six enzymes; it is only slightly deleterious for the more flexible human leukocyte elastase. The effect of gamma-branching (Ahx/Leu), of introduction of heteroatoms (Abu/Ser), (Ape/Hse), and (Ahx/Met), and of introduction of charge (Gln/Glu) and (Ahp/Lys) are tabulated and discussed. An important component of the free energy of interaction is the distortion of the binding pocket by bulky or branched side chains. Most of the variants studied were obtained by enzymatic semisynthesis. X18 variants of the 6-18 peptide GlyNH2 were synthesized and combined with natural reduced peptide 19-56. Disulfide bridges were formed. The GlyNH2 was removed and the reactive-site peptide bond X18-Glu19 was synthesized by complex formation with proteinase K. The resultant complexes were dissociated by sudden pH drop. This kinetically controlled dissociation afforded virgin, reactive-site intact inhibitor variants. PMID- 8495200 TI - Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from Thermus thermophilus: differences in dimer-dimer interaction. AB - The three-dimensional X-ray structure of a recombinant human mitochondrial manganese superoxide dismutase (MnSOD) (chain length 198 residues) was determined by the method of molecular replacement using the related structure of MnSOD from Thermus thermophilus as a search model. This tetrameric human MnSOD crystallizes in space group P2(1)2(1)2 with a dimer in the asymmetric unit (Wagner, U.G., Werber, M.M., Beck, Y., Hartman, J.R., Frolow, F., & Sussman, J.L., 1989, J. Mol. Biol. 206, 787-788). Refinement of the protein structure (3,148 atoms with Mn and no solvents), with restraints maintaining noncrystallographic symmetry, converged at an R-factor of 0.207 using all data from 8.0 to 3.2 A resolution and group thermal parameters. The monomer-monomer interactions typical of bacterial Fe- and Mn-containing SODs are retained in the human enzyme, but the dimer-dimer interactions that form the tetramer are very different from those found in the structure of MnSOD from T. thermophilus. In human MnSOD one of the dimers is rotated by 84 degrees relative to its equivalent in the thermophile enzyme. As a result the monomers are arranged in an approximately tetrahedral array, the dimer dimer packing is more intimate than observed in the bacterial MnSOD from T. thermophilus, and the dimers interdigitate. The metal-ligand interactions, determined by refinement and verified by computation of omit maps, are identical to those observed in T. thermophilus MnSOD. PMID- 8495201 TI - Stress and strain in staphylococcal nuclease. AB - Protein molecules generally adopt a tertiary structure in which all backbone and side chain conformations are arranged in local energy minima; however, in several well-refined protein structures examples of locally strained geometries, such as cis peptide bonds, have been observed. Staphylococcal nuclease A contains a single cis peptide bond between residues Lys 116 and Pro 117 within a type VIa beta-turn. Alternative native folded forms of nuclease A have been detected by NMR spectroscopy and attributed to a mixture of cis and trans isomers at the Lys 116-Pro 117 peptide bond. Analyses of nuclease variants K116G and K116A by NMR spectroscopy and X-ray crystallography are reported herein. The structure of K116A is indistinguishable from that of nuclease A, including a cis 116-117 peptide bond (92% populated in solution). The overall fold of K116G is also indistinguishable from nuclease A except in the region of the substitution (residues 112-117), which contains a predominantly trans Gly 116-Pro 117 peptide bond (80% populated in solution). Both Lys and Ala would be prohibited from adopting the backbone conformation of Gly 116 due to steric clashes between the beta-carbon and the surrounding residues. One explanation for these results is that the position of the ends of the residue 112-117 loop only allow trans conformations where the local backbone interactions associated with the phi and psi torsion angles are strained. When the 116-117 peptide bond is cis, less strained backbone conformations are available. Thus the relaxation of the backbone strain intrinsic to the trans conformation compensates for the energetically unfavorable cis X-Pro peptide bond. With the removal of the side chain from residue 116 (K116G), the backbone strain of the trans conformation is reduced to the point that the conformation associated with the cis peptide bond is no longer favorable. PMID- 8495202 TI - NMR analysis of staphylococcal nuclease thermal quench refolding kinetics. AB - Thermally unfolded staphylococcal nuclease has been rapidly quenched to temperatures near 0 degree C and the refolding behavior examined using an NMR kinetic experiment. Unfolded protein, exhibiting random coil chemical shifts, persists following the quench and refolds in two distinct kinetic phases. A protein folding intermediate with a trans Lys 116-Pro 117 peptide bond is transiently overpopulated and relaxes to the predominantly cis native cis-trans equilibrium. The rate of trans-->cis isomerization in the native-like nuclease intermediate is approximately 100-fold faster than that observed in a Lys-Pro model peptide. The activation enthalpy of 20 kcal/mol observed for the nuclease Lys 116-Pro 117 peptide bond is comparable to that observed for other X-Pro isomerizations. PMID- 8495203 TI - Site-directed mutagenesis to facilitate X-ray structural studies of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase. PMID- 8495204 TI - [Karyotype of moose (Alces alces L.) from northeastern Asia]. PMID- 8495205 TI - [Hyperventilation as a fundamental stimulator of pathological processes]. PMID- 8495206 TI - Mouse interferon gamma pretreated hepatocytes conditioned media suppress cytochrome P-450 induction by TCDD in mouse hepatoma cells. AB - Mouse interferon gamma (IFN-G) markedly suppressed 7-ethoxyresorufin o-deethylase (EROD) activity when added at the same time as TCDD in mouse primary hepatocyte cultures. IFN-G, however, had no effect on EROD induction by TCDD in Hepa-1 cells, a mouse hepatoma cell line, or Hepa-1 cells cocultured with Kupffer cells when added directly to the culture. EROD induction by TCDD in Hepa-1 cells was suppressed when cells were cultured with IFN-G pretreated mouse hepatocytes conditioned media. The magnitude of suppression was related to the dose of IFN-G and the density of hepatocytes used for the preparation of the conditioned media. Treatment of the monoclonal antibody against IFN-G to the conditioned media did not block the suppression of EROD induction. The suppressive effect of IFN-G pretreated hepatocytes conditioned media on EROD induction, however, was blocked when the conditioned media was heated or treated with trypsin. These results suggested that IFN-G pretreated mouse hepatocytes may release a soluble protein factor(s) which suppressed the EROD induction by TCDD in Hepa-1 cells. PMID- 8495207 TI - Regulation of rat growth hormone gene expression in tissue culture: influence of cell growth phase. AB - Regions of the rat growth hormone gene (rGH) upstream of the transcription initiation site were cloned upstream of the firefly luciferase reporter gene to study promoter activity in GH3 rat pituitary cells during lag, logarithmic and plateau phase cell growth. The region -1751bp to -1329 activated gene expression in lag phase cells, but was neutral during logarithmic and plateau phase cell growth. Sequences between -1329bp and -553 were inhibitory during lag and plateau phase growth, but activated promoter activity when introduced into cells during logarithmic growth. We conclude that the rGH 5' flanking DNA provides an interesting model to study DNA sequences involved in growth-related changes in promoter activity. PMID- 8495208 TI - Fusion of chromaffin granules with cardiolipin-containing phospholipid vesicles. AB - Fusion of chromaffin granule ghosts with model phospholipid vesicles is dependent on the composition of the vesicle membrane. Cardiolipin was found to make possible a process of fusion in the absence of calcium. This calcium-independent fusion appears to be partially protein-dependent. Upon interaction with pure cardiolipin vesicles calcium stimulates both fusion of chromaffin granule ghosts and release of catecholamines from intact chromaffin granules. We suggest that the release of catecholamines is not only a consequence of the fusion process. The relevance of protein-lipid interaction and the importance of the formation of HII phases or other non-lamellar phases, on the fusion of chromaffin granules are discussed. PMID- 8495209 TI - Mastoparan B, synthesis and its physical and biological properties. AB - Mastoparan B, a tetradecapeptide toxin (LKLKSIVSWAKKVL) isolated from the hornet (Vespa basalis) venom, was synthesized chemically. The physical and biological properties of both the native and synthetic peptides were studied and proved to be identical. Mastoparan B was found to have a potent antibacterial activity to both Gram negative and Gram positive bacteria. PMID- 8495210 TI - Partial oxidation of leucine in skeletal muscle. AB - 1. Leucine and its 2-oxo analogue, 4-methyl-2-oxopentanoate, increased the release of acetoacetate and 3-hydroxybutyrate from hemidiaphragms isolated from 40 h-starved rats. Glucose and lactate+pyruvate decreased basal and leucine stimulated rates of ketone body production. 2. The production of acetoacetate + 3 hydroxybutyrate in response to addition of leucine was suppressed in hemidiaphragms from fed rats. 3. At 3 mM leucine, for each mumol of leucine oxidized in the branched-chain 2-oxo acid dehydrogenase reaction (measured as 14CO2 production from [1-14C]leucine), 0.84 mumol of acetoacetate + 3 hydroxybutyrate were produced. This stoichiometry may imply that acetoacetate derived from the partial oxidation of leucine is not further oxidized in situ. The physiological significance of these findings is discussed. PMID- 8495211 TI - Acute ethanol intake produces lipid peroxidation in rat red blood cells membranes. AB - The effect of acute ethanol intake on lipid peroxidation (LP) and proteins in red blood cells (RBC) was explored. The amount of malondialdehyde (MDA; an indicator of LP) was elevated transiently when the maximal ethanol level in whole blood was observed. In contrast, erythrocyte membrane proteins were not affected. In in vitro experiments both ethanol and acetaldehyde did not alter the MDA levels. These results indicate that the metabolism of ethanol or acetaldehyde beyond the RBCs is required in order to detect LP on these cells. PMID- 8495212 TI - Partial purification and properties of ornithine carbamoyltransferase from Citrus limonum leaves. AB - Ornithine carbamoyltransferase (carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3) has been partially purified from C.limonum leaves. The data indicate the presence of only the anabolic enzyme. The activity is strongly influenced by pH, ionic strength and ornithine concentration. Optimal activity for the enzyme dissolved in the tri-buffer: diethanolamine,2-(N morpholino) ethanesulfonic acid, N-ethylenmorpholine (0.051 M/0.1 M/0.051 M) is at pH 9.0, when ornithine is 10 mM. The enzyme catalyses an ordered-sequential process in which carbamoyl phosphate binds first followed by L-ornithine and then L-citrulline leaves followed by phosphate. Support for this statement comes from product inhibition and evidence of abortive ternary complex formation. PMID- 8495213 TI - Failure in detecting mRNA transcripts from the mutated allele in myotonic dystrophy muscle. AB - The expression of myotonin-protein kinase (MT-PK) gene was studied in myotonic dystrophy (DM) muscle and normal controls using a polymerase chain reaction protocol to analyse the 3' intragenic p(CTG) polymorphism. Unaffected individuals show bi-allelic expression, while the sole wild-type allele was transcribed in DM muscle. Our findings support a gene dosage effect in the pathogenesis of the disease. PMID- 8495214 TI - Fe3+ binding to liposomes of different phospholipid composition. AB - The possibility that phospholipid polar heads may influence lipid peroxidation by affecting the binding and location of the metal catalyst was investigated. The multilamellar liposomes containing dimyristoyl phosphatidylcholine (DMPC) and an equal amount of either dipalmitoyl phosphatidylcholine (DPPC) or dipalmitoyl phosphatidic acid (DPPA) were utilized to study Fe3+ location. Two simple colorimetric methods were utilized, which were developed to evaluate: a) Fe3+ both sequestered within and bound in a non reducible form on the surface of the liposomes; Fe3+ chelated to strong complexing agents present both on the surface and in the inner compartment of the liposomes. The results obtained clearly show that the two types of polar heads differently bind the metal. Whereas DMPC/DPPC liposomes do not affect Fe3+ detection by both methods, suggesting that the metal is not internalized and strongly bound, DMPC/DPPA liposomes greatly interfere with Fe3+ detection. Analysis of the binding data indicates that a large amount of the metal is sequestered by the liposomes both in a complexed and free form. PMID- 8495215 TI - p-Bromophenacyl bromide potentiates hydrogen peroxide formation in human platelets challenged by thrombin and inhibits aggregation. AB - p-Bromophenacyl bromide, a potent alkylating agent inhibitor of phospholipase A2 and adenylate cyclase, potentiates hydrogen peroxide production in human platelets activated with thrombin. The maximal cooperative effect, specific for thrombin as inducer and potentiated by exogenous calcium, was observed at 2 microM BPB. Since it was shown that BPB is also a strong inhibitor of platelet aggregation (IC 50 = 3 +/- 1 microM) it is likely to suppose that the abnormal accumulation of hydrogen peroxide can influence platelet function. PMID- 8495216 TI - The generation of stable CHO cell lines expressing very high levels of complement C5A receptors and subsequent modulation of binding affinity for C5A. AB - A single gene fragment encoding for the C5a receptor was produced by reverse transcription of mRNA isolated from differentiated U937 cells and subsequently amplified by means of the polymerase chain reaction. This fragment was introduced into the mammalian expression vector pEE6hCMV.neo and used to transfect a CHO cell line constitutively expressing a viral transactivator protein. Binding characteristics identical to the native neutrophil receptor were observed. A combination of antibiotic selection and cell sorting using anti-C5a receptor antiserum were then used to generate stable cell lines expressing up to 1.2 x 10(7) functional C5a receptors/cell with a lower affinity for C5a. It is postulated that this modulation of receptor affinity is dependent on coupling to native G-proteins in the host cells. PMID- 8495217 TI - Effect of chronic intravenous injection of steroid hormones on body weight and composition of female rats. AB - The effects of the constant infusion with mini-osmotic pumps of several steroid hormones on body weight, energy balance and protein/lipid/water composition in young female rats has been studied for a period of 15 days. Despite unchanged food consumption, progesterone strongly induced fat deposition, with higher protein accrual efficiency coupled with lowered energy losses through thermogenesis. Estrogens lowered body weight but maintained higher protein levels and protein accrual rates; beta-estradiol induced the loss of lipid and diminished food intake. Heat production was unchanged or lower in all estrogen treated animals; beta-estradiol had a more marked effect on body weight (through food intake, heat production and lipid mobilization/storage combined) than estrone. Testosterone and 5-androstenediol increased the proportion of protein, but none of them had a significant effect on lipid deposition or heat production. Nortestosterone, increased energy expenditure, fuelled in part by a higher food ingestion, a trait shared by 4-androstenedione, but not by the other androgens. The effect of androgens on body weight may thus be a combination of their actions on a) food intake, b) efficiency of protein deposition and c) activation of heat production or of lipid (energy) storage. Practically all increased the efficiency of protein deposition. Nortestosterone increased heat production. Androstenedione increased lipid storage. Dehydroepiandrosterone did not decrease body weight or metabolic rate. Cortisol depressed heat production and food intake, with a net loss of weight. Cortisol and cortisone did not increase protein deposition, but corticosterone did; deoxycorticosterone showed a high efficiency of protein deposition and increased the size of fat stores, also increasing the metabolic rate by a mean 26% versus controls, compared with a reduction of about the same magnitude induced by cortisol. The data presented suggest that cortisol-cortisone and corticosterone may represent two distinct groups of glucocorticoids. PMID- 8495218 TI - Application of high performance liquid chromatography in study of sulphur amino acid metabolism in uremic patients. AB - High-performance liquid chromatography (HPLC) was used for the quantitation of the free amino acids in plasma and muscle samples from 34 patients with chronic renal failure; of these patients, 18 were treated by hemodialysis (HD) and 16 by continuous ambulatory peritoneal dialysis (CAPD). Depletion of taurine was observed in plasma and muscle of uremic patients, whereas methionine was normal. Cysteine sulphinic acid was present in plasma of all uremic patients. The results suggest that taurine depletion is due to decreased endogenous synthesis in uremic patients. PMID- 8495219 TI - Increased activity of FAD-linked glycerophosphate dehydrogenase in pancreatic islets of BB rats. AB - In several animal models of non-insulin-dependent diabetes, a decreased activity of FAD-linked glycerophosphate dehydrogenase was recently documented in pancreatic islet, but not liver, homogenates. The present study reveals that, on the contrary, the activity of the same mitochondrial enzyme is increased in islet, but not liver or spleen, homogenates of BB, as compared to BW, rats examined before the onset of severe hyperglycemia in this animal model of autoimmune insulin-dependent diabetes. PMID- 8495220 TI - Effect of anisotropic inhibitors of ATP synthesis in mitochondria of Saccharomyces cerevisiae. Comparison between a wild-type and a mutant strain altered in the stoichiometry of the MT DNA encoded proteolipids of ATP synthase. AB - The effect of a group of non-usual inhibitors of ATP synthesis was investigated in yeast mitochondria. Tetraphenylphosphonium, tetraphenylarsonium and ethidium decreased the rate of ATP synthesis but did not decrease the ATP/O ratio. They did not inhibit the ATPase activity and the translocase, and did not decrease the proton-motive force. They inhibited phosphate transport under conditions in which it was strictly energy-dependent, but did not under conditions in which it was energy-independent. These inhibitors had a poor effect on ATP synthesis in mitochondria isolated from a nuclear mutant which contained a reduced amount of the subunits 8 and 6 of the Fo part of the ATP synthase as compared to wild-type and which were unable to support any energy-dependent phosphate-transport. Thus, it appeared that the phosphate-dependence of ATP synthesis was altered in the same way by both tetraphenylphosphonium and the mutation. PMID- 8495221 TI - Suppression of the in vitro immune response by 7,12-dimethylbenz[a]anthracene in mouse splenocytes co-cultured with rat hepatocytes. AB - 7,12-Dimethylbenz[a]anthracene (DMBA) produced a dose-related suppression of in vitro polyclonal antibody response to lipopolysaccharide in mouse splenocytes co cultured with rat hepatocytes. Addition of alpha-naphthoflavone (ANF), the cytochrome P-450 inhibitor, to the coculture reversed the DMBA-induced immunosuppression. The amount of [3H]DMBA bound to splenocyte DNA increased in a time-dependent manner up to 4 hr of co-culture and treatment of ANF reduced the binding. The addition of extracellular DNA to the co-culture prevented the suppression of the antibody response by DMBA. These results suggested that reactive metabolite(s) of DMBA were released from hepatocytes and that the suppression of the antibody response by DMBA is mediated via these reactive intermediate(s). DNA represents the primary macromolecular target for the reactive intermediate(s) of DMBA. PMID- 8495222 TI - AIDS/HIV survey--Prince Edward Island. PMID- 8495223 TI - Effect of proposed change to the AIDS surveillance case definition on the epidemiologic profile of the HIV-seropositive population in southern Alberta. PMID- 8495224 TI - Heterosexual transmission of HIV--Puerto Rico, 1981-1991. PMID- 8495225 TI - Localisation of EGF-receptor mRNA in the nucleus of A431 cells by light microscopy. AB - We have localized the mRNA of the epidermal growth factor receptor (EGF-receptor) in nuclei of A431 cells by non-radioactive in situ hybridization at the light microscopical level using digoxigenin-labelled DNA probes. Both formaldehyde and glutaraldehyde fixations were tested before the hybridization was performed. Glutaraldehyde, compared with formaldehyde fixation, gives a less diffuse hybridization signal, which is easier to localize. Therefore, glutaraldehyde was used as a fixative in the hybridization experiments. It is demonstrated that the mRNA of the EGF-receptor is present in restricted domains mainly located around the nucleolus. This location of the EGF-receptor mRNA was unaltered after extraction of chromatin. Therefore it is concluded that the messenger RNA of the EGF-receptor is attached to the nuclear matrix. A possible biological role for the location of mRNA of the EGF-receptor around the nucleolus is discussed. PMID- 8495226 TI - Cell death in the salivary glands of metamorphosing Calliphora vomitoria. AB - The salivary gland cells of Calliphora vomitoria larvae initiate and complete their own destruction in a programmed manner at the onset of metamorphosis. On entering the post-feeding period the larvae come to rest and the polytene salivary gland cells show a significant increase in DNA synthesis followed closely by a surge of mRNA synthesis accompanied by increasing protein production. During this prelude to cell death the new mRNA gives rise to at least 10 new proteins. The first new proteins having a MWt between 30 and 100kD appear by day 8 of the life-cycle and a number persist until the advent of cell death on day 9. Other new proteins appear in a cascade of production during day 8 and in vitro translation of mRNA produced at this time shows a new 55kD protein appearing before cell destruction. Significantly no evidence of DNA degeneration or laddering associated with classical apoptosis was observed, on the contrary considerable DNA synthesis in the form of chromosomal endoduplication or "genomic amplification" was seen; selective gene expression being apparently controlled at translational level. Overall the results strongly suggest a synthetically mediated programmed cell death in the metamorphosing salivary glands of the blow fly which is distinct from apoptosis. PMID- 8495227 TI - Binding of low mobility group proteins with DNA examined in homologous and heterologous systems by gel retardation assay. AB - The interaction of low mobility group proteins (LMG), isolated from chromatin of pancreatic carcinoma cells (CAPAN-2), with fragments of 5'-flanking region of the antigen 17-1A gene was studied by gel retardation assay. The LMG proteins, which formed complexes with DNA were extracted from the gels and identified by polyacrylamide gel electrophoresis under denaturing conditions. The proteins of Mw about 100, 60, 55 and 48 kDa, which formed specific complexes with fragments of 5'-flanking region of the antigen 17-1A gene, were identified. PMID- 8495228 TI - Stimulation of human embryonic lung fibroblasts by TGF-beta and PDGF acting in synergism. The role of cell density. AB - The concerted action of TGF-beta and PDGF on a diploid human embryonic lung fibroblast cell strain (Flow 2002) grown in an homologous environment is investigated here. In sparse cultures, TGF-beta stimulates DNA synthesis over a broad concentration range (0.1-10 ng/ml). Furthermore, it acts in synergism with PDGF, a phenomenon which persists also during in vitro aging of the cells. Preincubation of TGF-beta with the fibroblasts up to 12 hours reduces the subsequent PDGF binding to the cells, while prolonged preincubation restores PDGF binding to control levels. Finally, in cultures of higher cell densities, TGF beta ceases to stimulate DNA synthesis, whereas PDGF continues even at cell confluency, retains its stimulatory activity suggesting different roles for the two growth factors during the wound healing process. PMID- 8495229 TI - Stimulation of DNA synthesis in skin fibroblasts by human hepatocyte growth factor/scatter factor. AB - The effect of hepatocyte growth factor/scatter factor (HGF/SF) on the proliferation of human skin fibroblasts was examined. At concentrations above 1.0 ng/ml, both native and recombinant human HGF/SF stimulated the DNA synthesis determined by [3H]thymidine incorporation, which was completely inhibited by an anti-human HGF/SF monoclonal antibody. The maximal DNA synthesis in the treated cells was nearly twice that in untreated cells. HGF/SF also caused an increase in the labelling index, DNA content and cell number. The effect of HGF/SF was more than additive to the maximal effect of insulin and epidermal growth factor, other mitogens for the fibroblasts. These results indicate that human skin fibroblasts are sensitive to the mitogenic action of HGF/SF. PMID- 8495230 TI - Staurosporine-induced morphological changes in the rat osteoblasts. AB - Treatment of cultured rat osteoblasts with staurosporine caused a rapid outgrowth of long slender cellular processes and the formation of stellate cells. The number of stellate cells increased with higher concentrations of and longer incubation with staurosporine. Scanning electron microscopy (SEM) revealed that the smooth surface of control polygonal cells became ruffled with many long slender cellular processes, thus increasing the cell surface area. Transmission electron microscopy (TEM) of the stellate cells showed a rich accumulation of large lipid droplets in the cytoplasm. Some lipid droplets had coalesced under the cytoplasmic membrane. We suggest that staurosporine has an effect on the differentiation of cultured rat osteoblasts. PMID- 8495231 TI - Changes in the concentration of ions during senescence of the human erythrocyte. AB - Flash frozen samples of normal human blood were cryosectioned and cryodried for electron probe x-ray microanalysis of the concentration of ions and elements in individual erythrocytes (RBCs). The data (expressed in mM/kg dry weight) demonstrated a systematic pattern of variation between the concentration of ions and elements in the RBCs. Specifically as K+ and Cl- decreased in concentration, Ca2+ and sulfur increased in concentration. Phosphorous, Na+ and Mg2+ did not demonstrate a significant pattern of change. These findings are related to the dehydration and to the volume decrease that accompanies senescence of the RBC. PMID- 8495232 TI - Immunoelectron microscopic localization of cytochrome P-450 isoenzyme CYP4A1 in liver, ileum and kidney of nafenopin treated male rats. AB - A monoclonal antibody raised against and specific for cytochrome P-450 isoenzyme CYP4A1 was used to investigate the subcellular distribution of this enzyme in the liver, kidney and ileum of nafenopin treated rats by means of immunoelectron microscopy. In the liver and kidney, labelling was restricted to peroxisomes and mitochondria of hepatocytes and proximal tubular epithelial cells whereas in ileum, immunolabelling was exclusively detected in mitochondria of absorptive cells. PMID- 8495233 TI - Radioligand and functional estimates of the interaction of the 1,4 dihydropyridines, isradipine and lacidipine, with calcium channels in smooth muscle. AB - 1. The present experiments were undertaken in order to characterize further the apparently irreversible inhibition of the contraction of depolarized rat aorta caused by lacidipine, a 1,4-dihydropyridine calcium antagonist. 2. We studied the effect of lacidipine on contraction evoked by 100 mM KCl solution in rat aorta, treated by N omega-nitro-L-arginine (0.1 mM), an inhibitor of nitric oxide (NO) synthesis. We compared the effect of prolonged depolarization on lacidipine and (+)-isradipine inhibition and the reversal of this inhibition after washout in the absence of dihydropyridines. Assuming that the onset of lacidipine-evoked inhibition was a pseudo-first order association kinetics, we estimated the dissociation rate constant (k-1 = 0.031 min-1), the association rate constant (k1 = 2.70 x 10(8) M-1 min-1) and the dissociation constant (KD = k-1/k1 = 115 pM) which was close to the IC50 value in steady-state conditions (160 pM). 3. The inhibitory effects of lacidipine and (+)-isradipine on rat aorta contraction were reversibly enhanced after preincubation with the drug in a 40 mM KCl-solution. Washout with drug-free 40 mM K(+)-depolarizing solution reversed inhibition in the (+)-isradipine-treated preparations, but not in the lacidipine-treated ones. 4. Radioligand binding studies were performed with [3H]-lacidipine and [3H] isradipine in microsomes from rat aorta and rat ileum. Both ligands bound to a homogeneous population of binding sites (for[3H]-lacidipine: KD = 23 +/- 2.6 pM, Bmax = 380 +/- 21 fmol mg-1 protein in membranes from aorta; KD =23 +/- 3.1 pM, Bmax = 790 +/- 60 fmol mg-1 protein in membranes from ileum; for [3H] isradipine:KD = 140 +/- 46 pM, Bmax = 350 +/- 64 fmol mg-1 protein in membrane from aorta; KD = 68 +/- 14 pM,Bmax = 760 +/- 75 fmol mg-1 protein in membranes from ileum). After isotopic dilution, [3H]-lacidipine and [3H]-isradipine dissociated according to a monoexponential kinetics. In membranes from ileum, the calculated dissociation rate constants (kappa_ 1) were 0.0257 min-1 and 0.0595 min-1, for [3H]-lacidipine and[3H]-isradipine, respectively.5. The non specific binding of [3H]-lacidipine and [3H]-isradipine, was measured in intact rat aorta preparations incubated under the conditions of the functional experiments, in the presence of nifedipine(1 microM). After incubation with [3H]-lacidipine 77.6 +/- 1.9 pM for 2 h the concentration of drug in the tissue was 15.15 +/- 1.18 fmol mg 1 w.wt. and still amounted to 7.24 +/- 0.61 fmol mg-1 w.wt. after 3.5 h washout in drug-free solution. After incubation with [3H]-isradipine 47.2 +/- 0.4 pM for 2 h it was 2.26 +/-0.07 fmol mg-1 w.wt. and was undetectable after 3.5 h washout in a drug-free solution.6. It is concluded that lacidipine interacts reversibly with dihydropyridine binding sites and that the apparent irreversible inhibition of contraction in depolarized preparations could be related to a nonspecific binding in a tissue compartment different from the plasma membrane. PMID- 8495234 TI - Effects of pH on the actions of dizocilpine at the N-methyl-D-aspartate receptor complex. AB - 1. The effects of varying pH from 6.5 to 7.4 and 8.0 on the actions of dizocilpine (MK801) on the N-methyl-D-aspartate (NMDA) receptor were investigated by use of a [3H]-dizocilpine binding assay and NMDA-induced intracellular free Ca2+ ([Ca2+]i) increases in cultured forebrain neurones. 2. Increasing pH from 6.5 to 8.0 significantly increased the rate of association and dissociation of [3H]-dizocilpine. The association process was better described by two rate constants under each condition, while only dissociation of [3H]-dizocilpine at pH 8.0 required two rate constants adequately to describe the curve. Equilibrium affinity of [3H]-dizocilpine was not altered by changing pH from 6.5 to 8.0. 3. NMDA and glycine together increased [Ca2+]i measured by fura-2 microspectrofluorimetry in single cultured neurones from rat forebrain. Compared to control response measured at pH 7.4, the combined effects of NMDA and glycine were reduced to 38.9% of control values by lowering pH to 6.5 and increased to 148.9% by raising pH to 8.0. 4. Dizocilpine (200 nM) effectively reversed increases in [Ca2+]i produced by NMDA together with glycine. The rate of reversal produced by this concentration of dizocilpine was considerably slower than that required for cells to recover to baseline following agonist removal. The rate at which dizocilpine reversed NMDA- and glycine-induced [Ca2+]i increases was not altered by raising pH from 6.5 to 8.0. 5. These data support the hypothesis that the rates associated with [3H]-dizocilpine binding are controlled by the level of activation of the receptor. In addition, these data confirm previous findings that NMDA responses are sensitive to small changes in pH.However, the lack of sensitivity to pH changes of dizocilpine inhibition of NMDA responses show that other factors are also important in controlling the action of channel-blocking NMDA receptor antagonists. PMID- 8495235 TI - Calcium antagonistic and antiarrhythmic actions of CPU-23, a substituted tetrahydroisoquinoline. AB - 1. The effects of CPU-23 (1-(1-[(6-methoxyl)-naphth-2-yl])-propyl-2-(1 piperidine)-acetyl-6 ,7- dimethyoxy-1,2,3,4-tetra-hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone-anaesthetized rats subjected to coronary artery ligation were also evaluated. 2. CPU-23 at 10(-6)-10(-4) M markedly inhibited slow action potential characteristics in guinea-pig papillary muscles and pace-maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10(-4) M. None of the effects of CPU-23 was reversed by washout for up to 2 h. 3. Like nifedipine and diltiazem, CPU-23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose-dependently inhibited the force of contraction, CPU-23 inhibited and stimulated the force of contraction at 10(-7)-3 x 10(-6) M and 10( 5) M, respectively. 4. CPU-23 at 10(-6)-10(-5) M inhibited the KCl-induced [Ca2+]i increase in the Ca2+ medium, but did not affect the caffeine-induced [Ca2+]i increase in the Ca(2+)-free medium in isolated ventricular myocytes. 5. CPU-23 at 1-5 mg kg-1 reduced dose-dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5-5 mg kg-1 it even abolished VF, which was accompanied by 100% survival. 6. It is suggested that CPU-23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2+ through Ca2+ channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias. PMID- 8495236 TI - Blockade by calmodulin inhibitors of Ca2+ channels in smooth muscle from rat vas deferens. AB - 1. Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W-7 and calmidazolium) on Ca2+ channels were investigated in smooth muscle from rat vas deferens. 2. All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7 mM). The order of potency for the relaxation was trifluoperazine > W-7 > calmidazolium. 3. In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [3H]-nimodipine binding. Trifluoperazine and W-7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation. 4. Ba2+ current flowing through voltage-gated Ca2+ channels was measured under whole-cell voltage-clamp conditions in isolated smooth muscle cells. The Ba2+ current was suppressed by the three calmodulin inhibitors in the concentration-range where inhibition of [3H]-nimodipine binding was observed. Neither voltage-dependence nor the inactivation time course of Ba2+ current were affected by these compounds. 5. The results suggest that the calmodulin inhibitors directly block Ca2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W-7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds. PMID- 8495237 TI - Role of angiotensin AT1 and AT2 receptors in mediating the renal effects of angiotensin II in the anaesthetized dog. AB - 1. Experiments were performed using the selective AT1 receptor antagonist, GR117289, and the selective AT2 receptor antagonist, PD123177, to assess the relative importance of AT1 versus AT2 receptors in mediating the renal effects of angiotensin II (AII) in vivo, in salt-replete pentobarbitone-anaesthetized dogs. 2. The AT1 receptor antagonist, GR117289 (0.5 mg kg-1 + 1 microgram kg-1 min-1, i.v.), caused renal vasodilatation, characterized by a mean increase of 21 +/- 5% in renal blood flow, 45 min post-dose. GR117289 also caused a fall in mean blood pressure (12 +/- 4%), but despite this, sodium and urine excretion were not reduced. Indeed, there was a tendency for urine output and sodium excretion to increase, although the changes were not statistically significant. GR117289 caused a reduction in plasma aldosterone levels (-35 +/- 16%) 45 min post-dose, despite increasing plasma renin activity (+ 173 +/- 42%). In contrast to GR117289, the AT2 receptor antagonist, PD123177 (20 micrograms kg-1 min-1 intra renal artery; i.r.a.) caused no significant change in blood pressure, renal blood flow, or sodium and urine excretion, indicating that the renal effects of endogenous AII in these salt-replete animals are mediated predominantly by AT1 receptors. 3. Intra-renal artery infusion of AII (1-300 ng kg-1 min-1) caused dose-related renal vasoconstriction, and decreases in urine output, sodium excretion, fractional excretion of sodium, and glomerular filtration rate (GFR). The AT1 receptor antagonist, GRI 17289 (0.5 mg kg-1 + 1 microg kg-1 min-1, i.v.)antagonized these renal effects of AII, causing 15-38 fold rightward displacements of mean dose response curves for these parameters. In contrast, PD123177 (20 microg kg-1 min-1, i.r.a.) failed to antagonize the renal haemodynamic and excretory effects of lower doses of All (1-10 ng kg-1 min 1,i.r.a.). However, at higher doses of AII (30-300 ng kg-l min-1, i.r.a.), while PD123177 still failed to antagonize the effects of the peptide on urine output, sodium excretion and GFR, it did cause a small,but significant, degree of inhibition of All-induced renal vasoconstriction. In addition, at a higher dose(50 microg kg-1 min-1, i.r.a.), PD123177 caused a greater degree of antagonism of AII-induced renal vasoconstriction, while renal excretory responses to AII remained unaffected.4. This study shows that the renal haemodynamic and excretory effects of AII in salt-replete anaesthetized dogs are mainly mediated by angiotensin AT1 receptors. However, the inhibitory effect of PD123177 on renal vasoconstrictor responses to high doses of AII, raises the possibility that functionally important AT2 receptors are present in the canine renal vasculature. PMID- 8495238 TI - A comparison of rat brain amino acid and monoamine content in diazepam withdrawal and after exposure to a phobic stimulus. AB - 1. The content of amino acids (taurine, glycine, glutamic acid, gamma aminobutyric acid (GABA) and aspartic acid) and monoamines (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline) in homogenates of rat cortical and hippocampal tissue were measured by high performance liquid chromatography (h.p.l.c.) with fluorescent and electrochemical detection respectively, after two anxiogenic treatments: exposure to a phobic stimulus (cat odour) and withdrawal from chronic diazepam treatment. 2. In neither of the two anxiogenic situations was there a significant change in any amino acid content, in either brain area. 3. In the group withdrawn from chronic diazepam, cortical 5 HT and 5-HIAA levels and hippocampal 5-HT levels were significantly increased. Noradrenaline content was significantly decreased in the hippocampus. 4. The changes in 5-HT and 5-HIAA levels following cat odour exposure were area-specific in that they decreased in the hippocampus, but increased in the cortex. 5. Following cat odour exposure, noradrenaline levels appeared not to change in either area studied. However during exposure to cat odour, it was found that half the animals avoided the odour source and half were indifferent. The animals showing marked avoidance had significantly higher cortical noradrenaline content and this was significantly different from control, whereas hippocampal noradrenaline levels were not dependent upon the differences in avoidance of the odour source. 6. The results show clearly different neurochemical changes in the rat following exposure to a phobic stimulus and withdrawal from diazepam. It is hoped comparative studies such as this will enable better understanding of anxiety states in the rat which could parallel the different classes of anxiety recognised in the clinic PMID- 8495239 TI - Stimulation of insulin secretion and improvement of glucose tolerance in rat and dog by the P2y-purinoceptor agonist, adenosine-5'-O-(2-thiodiphosphate). AB - 1. In vivo effect of a P2y-purinoceptor agonist, adenosine-5'-O-(2 thiodiphosphate) (ADP beta S), on insulin secretion and glycaemia were studied both in rats and dogs. 2. In anaesthetized rats, i.v. administered ADP beta S (0.2 mg kg-1) produced an insulin response dependent on the nutritional state of the animals, since we observed only a transient increase in overnight-fasted rats and a sustained insulin secretion followed by a reduction in plasma glucose levels in fed rats. During an i.v. glucose tolerance test, ADP beta S enhanced insulin release and thus increased the glucose disappearance rate. 3. In anaesthetized fasted dogs, i.v. administered ADP beta S (0.1 mg kg-1) increased pancreaticoduodenal insulin output and slightly decreased blood glucose levels. 4. In conscious fasted dogs, orally administered ADP beta S (0.1 mg kg-1) transiently increased insulinemia and punctually reduced glycaemia. Furthermore, during an oral glucose tolerance test, orally administered ADP beta S at the same dose markedly enhanced insulin secretion and consequently reduced the hyperglycaemia. 5. In conclusion, the P2y-agonist, ADP beta S, is a potent insulin secretagogue in vivo, improves glucose tolerance and is effective after oral administration. Thus, the P2y-purinoceptors of the beta cell may be a target for new antidiabetic drugs. PMID- 8495240 TI - Contractile and relaxant effects of phorbol ester in the intestinal smooth muscle of guinea-pig taenia caeci. AB - 1. Effects of phorbol esters on the cytosolic Ca2+ level ([Ca2+]i) and muscle tension in the intestinal smooth muscle of guinea-pig taenia caeci were examined. 2. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 microM) did not change the [Ca2+]i and tension in resting muscle. 3. In high K(+)-stimulated muscle, 1 microM DPB transiently augmented the contraction and decreased [Ca2+]i. 12-Deoxyphorbol 13 isobutyrate 20-acetate (1 microM) and phorbol 12, 13-dibutyrate (1 microM) showed similar effects to DPB whereas phorbol 12-myristate 13-acetate (1 microM) and phorbol 12, 13-didecanoate (1 microM) were ineffective. 4. DPB (1 microM) inhibited both [Ca2+]i and tension stimulated by 300 nM carbachol or 3 microM histamine. In the presence of a higher concentration of carbachol (1 microM), DPB decreased [Ca2+]i and transiently increased muscle tension. 5. In the muscle strips permeabilized with bacterial alpha-toxin, 1 microM DPB shifted the Ca(2+) tension curve to the left. An inhibitor of protein kinase C, H-7 (30 microM), inhibited the effect of DPB. 6. DPB did not change the high K(+)-induced contraction in the muscle strips pretreated with 3 microM phorbol 12-myristate 13 acetate for 24 h. 7. These results suggest that activation of protein kinase C has dual effects; it augments contraction by increasing the Ca2+ sensitivity of the contractile elements and it inhibits contraction by decreasing [Ca2+]i. PMID- 8495241 TI - Role of platelet-activating factor (PAF) in platelet accumulation in rabbit skin: effect of the novel long-acting PAF antagonist, UK-74,505. AB - 1. The contribution of platelet-activating factor (PAF) to platelet deposition and oedema formation induced by exogenous soluble mediators, zymosan particles and associated with a reversed passive Arthus (RPA) reaction in rabbit skin was investigated by use of a novel long-acting PAF receptor antagonist, UK-74,505. 2. Oedema formation and platelet accumulation were simultaneously measured by i.v. injection of [125I]-albumin and 111In-labelled rabbit platelets. UK-74,505 was either administered i.v. or used to pretreat radiolabelled platelets in vitro before their injection into recipient animals. Platelets pretreated with UK 74,505 were also labelled with the fluorescent calcium indicator, Fura-2, to assess their ex vivo reactivity to PAF at the end of the in vivo experiment. 3. UK-74,505 (0.5 mg kg-1), administered i.v., inhibited PAF-induced oedema formation, but did not affect oedema induced by zymosan particles, bradykinin (BK), histamine, formyl-methionyl-leucylphenylalanine (FMLP), zymosan-activated plasma (ZAP, as a source of C5a des Arg), leukotriene B4 (LTB4) or interleukin-8 (IL-8). 4. UK-74,505, administered i.v. also suppressed the small platelet accumulation induced by exogenous PAF, but had no effect on accumulation induced by IL-8 or ZAP. Although oedema induced by zymosan was not affected by i.v. UK 74,505, zymosan-induced platelet accumulation was significantly attenuated by the antagonist. 5. The RPA reaction in rabbit skin was associated with marked oedema formation and platelet accumulation which were both inhibited by i.v. UK-74,505. 6. In vitro, UK-74,505 inhibited aggregation and the increase in intracellular calcium concentration induced by PAF in rabbit washed platelets in a concentration-dependent manner (IC50 = 1.6 x 10-8 M and 1.1 x 10-8 M, respectively). Platelets pretreated with 10-6 M UK-74,505, and maintained at 37 degrees C,were unresponsive to PAF, whilst responding normally to thrombin, for up to 4 h.7. In a second series of in vivo experiments, platelets were labelled with 111In and loaded with Fura-2.The platelets were then pretreated with 10-6 M UK-74,505, washed, and injected into recipient rabbits.These platelets, prepared from blood samples taken at the end of the in vivo experiments, exhibited an 80% reduction in their response to PAF as measured ex vivo with Fura-2. However, in contrast to the effects of i.v. UK-74,505, platelets pretreated with the antagonist did accumulate effectively in the RPA reaction, a significant reduction only being observed in responses at the lowest antibody dose. In addition, pretreatment of platelets had no effect on the small platelet accumulation induced by PAF.8. These results suggest that PAF is an important mediator of oedema formation and platelet accumulation in the RPA reaction in rabbit skin. However, they question the role of PAF receptors on platelets in this model. The results also indicate that PAF may be involved in platelet accumulation induced by zymosan in rabbit skin. PMID- 8495242 TI - Effects of vasoactive intestinal polypeptide on antigen-induced bronchoconstriction and thromboxane release in guinea-pig lung. AB - 1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5 lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/ 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge. 6. The administration of exogenous VIP as a continuous infusion (10-8 M) attenuated the bronchoconstriction and the release of cyclo-oxygenase metabolites following antigen challenge.7. Acetylcholine (10-6-l0-5 M) infused into the pulmonary artery induced a dose-dependent bronchoconstriction not associated with enhanced VIP or TXB2 release.8. The TXA2 mimetic U-46619 (0.1-1.0 nmol) caused dose dependent increases in airway resistance,concomitant with an up to 10 fold increase in VIP release. VIP inhibited arachidonate-induced in vitro aggregation of washed rabbit platelets in a dose-dependent manner over a dose range 10-8 10-6 M.Despite the antiaggregatory effect of VIP, TXB2 and PGE2 synthesis was reduced only to a minor extent,and there was no redirection of arachidonate metabolism from TXA2 to PGE2, indicating that VIP does not act as a TX synthase inhibitor in vitro.9. We conclude that VIP may play a role in regulating bronchial smooth muscle reactivity in lung anaphylaxis by inhibiting the synthesis and release of TXA2, a potent vasoactive and bronchoconstrictor agent. TXA2, on the other hand, strongly enhances neuronal VIP release. PMID- 8495243 TI - The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist. AB - 1. The diuretic effect of the selective A1 adenosine receptor antagonist, 8 cyclopentyl-1,3-dipropylxanthine (CPX), was investigated in anaesthetized rats. 2. CPX (0.1 mg kg-1, i.v.) produced significant increases in urine flow, and the excretion rate and fractional excretion of both sodium and chloride. By contrast, CPX administration did not result in any significant change in the excretion of potassium. 3. The diuretic effect of CPX was accompanied by a transient increase in inulin clearance although p-amino-hippurate clearance was unaffected, indicating the CPX induced a temporary elevation of glomerular filtration rate but no change in renal blood flow. 4. The fractional excretion of lithium (a marker of delivery of fluid out of the proximal tubule) was also significantly increased by CPX. However, other measures of tubular function derived from lithium clearance indicated that there were no changes in the handling of sodium or water in the distal regions of the nephron. 5. CPX did not significantly alter the relationship between either free water reabsorption or free water clearance and the distal delivery of sodium, which suggests that CPX does not affect the renal concentration/dilution mechanism. 6. The results of this study show that the diuresis and increased excretion of sodium and chloride induced by CPX (0.1 mg kg-1) in the rat, occurs with only transient elevation in glomerular filtration rate and no change in renal blood flow. The primary reason for the diuresis appears to be inhibition of sodium reabsorption in the proximal tubule. Furthermore, the results provide evidence that production and release of endogenous adenosine modifies renal excretory function via stimulation of the A1 receptor subtype. PMID- 8495244 TI - Ca(2+)-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate. AB - 1. Administration of maitotoxin (MTX), a dinoflagellate toxin, caused aggregation of rabbit washed platelets. The cytosolic Ca2+ concentration ([Ca2+]i), measured by fura-2 fluorescence technique, was also increased by the presence of MTX. Rates of aggregation response and [Ca2+]i-increase were dependent on tested concentrations (3-100 ng ml-1) of the toxin. 2. The MTX-induced platelet aggregation and [Ca2+]i-increase were totally abolished in a Ca(2+)-free solution. The successive administration of Ca2+ in the presence of MTX elicited the aggregation and increase in [Ca2+]i. 3. Ba2+ was capable of substituting for Ca2+ in the MTX-induced platelet aggregation. In the presence of external Ca2+, transition metals, Co2+, Cd2+ and Ni2+, inhibited the aggregation response to MTX. 4. Organic calcium antagonists (verapamil and nifedipine) as well as a cyclo oxygenase-inhibitor (aspirin) did not apparently inhibit the aggregation response to MTX, except for a high concentration (10(-5) M) of verapamil, while procaine (10 mM) reduced the rate of platelet aggregation. 5. MTX also elicited a release of ATP from platelets, which was abolished in the absence of external Ca2+. 6. In contrast, thrombin 0.5 unit ml-1 could elicit platelet shape change, [Ca2+]i increase and ATP-release in the absence of external Ca2+. 7. These results suggest that the MTX-induced platelet activation is caused by an enhanced Ca(2+) influx presumably through voltage-independent Ca2+ channels on the plasma membrane. PMID- 8495245 TI - Adenosine A3 receptors mediate hypotension in the angiotensin II-supported circulation of the pithed rat. AB - The cardiovascular effects of N6-2-(4-aminophenyl)ethyladenosine (APNEA), which when radiolabelled with 125I shows high affinity for the newly described adenosine A3 receptor, have been investigated in the angiotensin II-supported circulation of the pithed rat. APNEA induces hypotensive responses which are unaffected by high doses (20-40 mg kg-1) of the broad spectrum, adenosine receptor antagonist, 8-(p-sulphophenyl)theophylline (8-SPT). 8-SPT-resistant falls in blood pressure are also seen, in the absence of bradycardia, with 5'-N ethylcarboxamidoadenosine (NECA) and the R- and S-enantiomers of N6 phenylisopropyladenosine (PIA). Xanthine insensitivity, high potencies of APNEA, NECA and R-PIA, and an enantiomeric selectivity favouring R- over S-PIA are distinguishing features of the adenosine A3 receptor. We suggest that hypotension in the pithed rat may be a functional correlate of this site. PMID- 8495246 TI - Functional characterization of muscarinic receptors in murine airways. AB - 1. The effects of muscarinic receptor antagonists considered to be selective for M1 receptors (pirenzepine; PZ), M2 receptors (AFDX-116), and for M3 receptors (4 diphenyl acetoxy N-methyl-piperidine (4-DAMP)) were used to investigate the existence of muscarinic receptors subtypes in murine airways. Atropine was used as a nonselective antagonist. The effects of these antagonists were studied upon tracheal contractions induced either by EFS (electric field stimulation) or by application of an exogenous cholinoceptor agonist (arecoline). 2. The muscarinic receptor antagonists tested inhibited arecoline-induced tracheal contractions with the following rank order of potency: 4-DAMP = atropine > pirenzepine = AFDX 116. The rank order of potency of the muscarinic antagonists used in inhibiting EFS-induced tracheal contractions was: 4-DAMP = atropine > PZ > AFDX-116. The pA2 values for these antagonists were similar when compared to the pA2 values determined in guinea-pig and bovine airway smooth muscle. 3. In addition to in vitro studies, the effects of inhalation of the different muscarinic antagonists on lung function parameters in vivo were investigated. Inhalation of 4-DAMP induced a decrease in airway resistance and an increase in lung compliance. In contrast, inhalation of AFDX-116 induced an increase in airway resistance and almost no change in lung compliance. Apart from some minor effects of atropine on airway resistance, atropine, PZ, and pilocarpine failed to induce changes in lung mechanics as determined by in vivo lung function measurements. 4. The results provide evidence for the existence of M3 receptors on murine tracheae that are involved in the contraction of tracheal smooth muscle. This is in agreement with other animal species such as the guinea-pig and bovine. In vivo experiments also demonstrated that in the mouse, M3 receptors play an important role in bronchial smooth muscle contraction and thus in bronchoconstriction. Interestingly we have also demonstrated that M2 receptors can play a role in bronchodilatation. Inhalation of an M2 receptor antagonist induced an increase in airway resistance whereas inhalation of an M3 receptor antagonist induced a decrease in airway resistance. It is therefore likely that an M3/M2 receptor balance plays an important role in the regulation of airway function. PMID- 8495247 TI - Role of the endothelium in the response to cholinoceptor stimulation of rabbit ear and femoral arteries during cooling. AB - 1. The role of the endothelium in the effects of cooling on the response to cholinoceptor stimulation of the rabbit central ear (cutaneous) and femoral (non cutaneous) arteries was studied using 2 mm long cylindrical segments. 2. Concentration-response curves for acetylcholine (10(-9)-10(-5) M), methacholine (10(-9)-10(-5) M) and sodium nitroprusside (10(-9)-10(-4) M) were isometrically recorded in arteries under conditions, with and without endothelium or following pretreatment with the nitric oxide-synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-6)-3 x 10(-4) M) at 37 degrees C and at 24 degrees C (cooling). 3. Ear and femoral arteries showed endothelium-dependent relaxation to acetylcholine and methacholine at 37 degrees C and 24 degrees C. The extent of relaxation of the control ear arteries, but not of the control femoral arteries, to acetylcholine and methacholine increased during cooling. 4. L-NAME (10(-6)-3 x 10(-4) M) reduced in a concentration-dependent way the response of ear arteries to acetylcholine at both 37 degrees C and 24 degrees C, this reduction being more potent at 37 degrees C. L-Arginine (10(-5)-10(-3) M) reversed in a concentration dependent manner the inhibitor effects of 10(-5) M L-NAME at both temperatures. 5. Sodium nitroprusside caused a concentration-dependent relaxation in both arteries that was endothelium-independent. However, the extent of relaxation to this nitrovasodilator in ear and femoral arteries was lower at 24 degrees C. 6. These results suggest that cooling augments the reactivity of cutaneous (ear) arteries, but not that of non-cutaneous (femoral) arteries to cholinoceptor stimulation by endothelium-mediated mechanisms.Cooling could therefore facilitate the stimulated release of endothelial nitric oxide in cutaneous vessels. PMID- 8495248 TI - Endothelin (16-21): biphasic effect and no desensitization on the guinea-pig isolated ileum. AB - 1. In the guinea-pig ileum the C-terminal hexapeptide of the endothelins, endothelin (16-21), induced a biphasic effect (relaxation followed by contraction) qualitatively similar to that seen in the responses to endothelins 1 and 3. Both components of the response were concentration-dependent in the range studied (2-100 microM). 2. The response induced by endothelin (16-21) was inhibited in low-sodium (80 mM) medium. 3. Repeated administration of endothelin (16-21) induced no desensitization of the preparation, contrasting with the tachyphylaxis induced by endothelin-1 and endothelin-3 in the guinea-pig ileum. 4. Tissues rendered tachyphylatic to endothelin-1 or endothelin-3 responded normally to endothelin (16-21). 5. The results suggest that the C-terminal tail of the endothelins contains the message for the biphasic response, whereas the N terminal domain may be responsible for the strong binding to the receptor and for the tachyphylactic properties of endothelin-1 and endothelin-3, in the guinea-pig isolated ileum. However, the possibility that endothelin (16-21) may be acting on a site other than the endothelin receptor cannot be ruled out. PMID- 8495249 TI - Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro. AB - 1. The actions of the following pyrogens: lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly-I:C), human interleukin (IL)-1 alpha and IL 1 beta, human IL-6 and rat interferon (INF) on corticotrophin-releasing factor-41 (CRF-41) and prostaglandin E2 (PGE2) release from the intact rat hypothalamus in vitro have been studied. 2. Rat hypothalami were incubated in vitro in an artificial cerebrospinal fluid. Immunoreactive (ir)-CFR-41 and PGE2 released into the medium were measured by two-site enzyme amplified immunometric assay (EAIA) and radioimmunoassay (RIA) respectively. 3. Human IL-6 (1 to 10,000 IU ml-1) caused a dose-dependent release of irCRF-41, rising to a maximal 3-4 fold increase over basal at the highest dose tested. Human IL-1 alpha (1 to 1000 IU ml 1), human IL-1 beta (1 to 1000 IU ml-1), poly-I:C (10 pg ml-1 to 100 micrograms ml-1) and rat INF (1 to 10,000 IRu ml-1) all failed to alter irCRF-41 release. 4. LPS (1 mg ml-1) caused a 35% decrease in irCRF-41 release; however, over the dose range of 0.1 microgram ml-1 to 100 micrograms ml-1, LPS failed to alter irCRF-41 release. The decreased irCRF-41 release in response to LPS (1 mg ml-1) was accompanied by a decrease in the subsequent 56 mM KCl stimulation of irCRF-41. 5. Human IL-1 alpha and IL-1 beta (1000 IU ml-1) were able to stimulate the release of irPGE2 from intact hypothalami, causing a 2 fold increase over basal release. Poly-I:C (100 microg ml-1), LPS (0.1 microg ml-1 to 1 mg ml-1), rat INF (10,000 IRu ml-1) and human IL-6 (1 to 10,000 iu ml-1) all failed to alter irPGE2release.6. In conclusion, these results suggest that the in vitro release of CRF-41 and PGE2, in response to pyrogens, are mediated via different cytokines. In view of this it is possible that different cytokines may mediate the temperature, prostaglandin and hypothalamo-pituitary-adrenocortical axis activation seen during pyrogenic stimulation in vivo. PMID- 8495250 TI - The Leu13-motilin (KW-5139)-evoked release of acetylcholine from enteric neurones in the rabbit duodenum. AB - 1. Involvement of cholinergic mechanisms in the contractile response to Leu13 motilin (LMT, KW-5139) was investigated in rabbit duodenal segments, and longitudinal muscle-myenteric plexus (LM-MP) preparations preincubated wtih [3H] choline. 2. Contractile response to LMT (0.1 nM-1 microM) consisted of an initial rapid (phasic) contraction and a tonic contraction slowly fading to a sustained plateau. LMT caused a concentration-dependent phasic contraction of rabbit isolated duodenal segments. The EC50 value was 2.5 nM and the maximum amplitude of the contraction was 103% of the response induced by acetylcholine (ACh, 100 microM). Neither tetrodotoxin nor atropine changed the EC50 value or the maximum amplitude of the response to LMT. 3. Both atropine and tetrodotoxin decreased the amplitude and accelerated fading of the tonic contraction produced by LMT. 4. LMT (30 nM-3 microM) induced an increase of 3H-outflow, in a concentration-dependent manner. The LMT-induced increase of 3H-outflow was prevented by removal of external Ca2+ or by the presence of tetrodotoxin. 5. Porcine motilin (10 nM-1 microM) also stimulated the release of 3H at a similar concentration-range to that seen with LMT. 6. Pretreatment with LMT (3 microM for 20 min) decreased LMT- and the porcine motilin-evoked release of 3H but did not alter the high K(+) evoked release. 7. Our results suggest that LMT and porcine motilin stimulate the release of ACh from enteric neurones through the same receptor, and that the release of ACh plays a role in tonic components of contraction in the rabbit duodenum. PMID- 8495251 TI - The clinical assessment of the scleroderma spectrum disorders. PMID- 8495252 TI - Cytotoxic therapy in rheumatoid arthritis. PMID- 8495253 TI - Validity and reliability of three methods used in the diagnosis of Raynaud's phenomenon. The UK Scleroderma Study Group. AB - Three different assessment methods for the classification of Raynaud's phenomenon (RP) were compared. These were (i) a previously validated method using colour charts supplemented with a short questionnaire, (ii) answers to a questionnaire based on criteria derived from the consensus opinion of a group of clinicians, and (iii) individual clinician's assessment using standard descriptions based upon the same consensus view. We report the results of a study involving six clinicians and 30 subjects investigating the level of repeatability between the three methods and also the reliability between the six clinicians. There did not exist any overall systematic bias between the six clinicians. Further, agreement between them, as assessed by the kappa statistic, ranged from moderate to good. However, there did exist systematic bias between the results from all three of the classification approaches with agreement between them ranging from only poor to moderate. We conclude that the previously validated colour chart assessment is too insensitive to detect RP. Further, a structured questionnaire based on perceived clinician's opinion could not reproduce clinicians' classification in practice. By contrast, supplying clinicians with standard descriptions did yield a reliable classification system for RP. PMID- 8495254 TI - Anti-DNA antibodies in the primary antiphospholipid syndrome (PAPS) AB - Primary antiphospholipid syndrome (PAPS) is considered a distinct entity from SLE and patients with PAPS are generally regarded as being dsDNA antibody negative. Levels of IgG and IgM ss and ds DNA antibodies were measured by ELISA in 30 patients who fulfilled the criteria for the diagnosis of PAPS. We compared these patients with 20 normal controls and seven patients with idiopathic SLE. We also examined all the sera for anti-nuclear antibodies by Hep-2 cells and for dsDNA antibodies by Crithidia. We found that 16 patients with PAPS had antibodies to ss and/or dsDNA. Only three of the 16 positive patients had both IgG and IgM anti DNA antibodies. Twelve patients had anti-nuclear antibodies, but only two were weakly positive for dsDNA antibodies by Crithidia immunofluorescence. Eleven out of 30 patients with PAPS had IgM anti-dsDNA antibodies compared to two out of the seven SLE patients. The PAPS patients with anti-DNA antibodies were clinically indistinguishable from the PAPS patients without antibodies against DNA. Our results show that 53% of patients with PAPS had antibodies to DNA which supports the view that PAPS and SLE are probably overlapping disorders. PMID- 8495255 TI - Is osteoarthritis in women affected by hormonal changes or smoking? AB - The influence of sex hormone related events and smoking on the development of OA in women was investigated in a case-controlled postal survey. One hundred and twenty-nine patients with nodal generalized osteoarthritis (NGOA) and 145 with non-nodal pauciarticular large joint osteoarthritis (LJOA) were identified from the database of a Nottingham OA clinic. For each patient, three age-matched controls were randomly selected from the same general practice. Sixty-three per cent of questionnaires (690/1096) were returned: NGOA, 95; NGOA controls, 226; LJOA, 113; LJOA controls, 256. There were no differences in age at menarche or menopause, rates of hysterectomy, oral contraceptive use, or hormone replacement use between cases and controls. Fewer OA patients had ever smoked [(Odds Ratio (OR) 0.65, 95% Confidence Interval (CI) 0.45-0.95)] and subset analysis demonstrated that this negative association occurred only in the LJOA group (OR 0.43, CI 0.25-0.72), particularly in those with knee OA (OR 0.29, CI 0.14-0.62). A previous successful pregnancy was negatively associated with NGOA (OR 0.47, CI 0.24-0.95). This study demonstrates no association between oestrogen-related hormonal events and OA, but a negative association between smoking and LJOA. Such data supports the concept that OA is a heterogeneous disease and underlines the need to differentiate OA subsets. PMID- 8495256 TI - The frequency of extremely low serum pepsinogen, indicative of corpus gastritis with severe atrophy, in rheumatoid arthritis, other chronic rheumatic diseases and non-rheumatic diseases. AB - The aim of this study was to assess the frequency of corpus gastritis with severe atrophy (CGA), pernicious anaemia and combined severe atrophy of antrum and corpus by non-invasive methods (i.e. determination of low serum pepsinogen A (PgA) and serum gastrin) in outpatients with RA (n = 249), compared to outpatients with other rheumatic diseases (n = 181) and outpatients with chronic non-rheumatic diseases (n = 429). In addition we investigated whether NSAIDs could cause or prevent CGA. A low serum PgA level (< 17 micrograms/l), indicating pentagastrin-refractory achlorhydria in patients without gastric resection, was found in 13 patients (5.2%; 95% Confidence Interval (CI) 2.4-8.0) with RA, in 11 (6.1%; 95% CI 2.6-9.5) with other rheumatic diseases and in 12 patients (2.8%; 95% CI 1.2-4.4) with chronic non-rheumatic diseases (NS). Low serum PgA values were more frequent in older patients (P < 0.005) and females (P < 0.05). Pernicious anaemia occurred in RA in 1.2% (95% CI 0-2.6) of the patients while for other rheumatic diseases the frequency was 1.7% (95% CI 0-3.5) and for chronic non-rheumatic diseases 0.2% (95% CI 0-3.6) (NS). In patients with a serum PgA below 17 micrograms/l, normal serum gastrin levels (< 90 ng/l) as an indication of combined severe atrophy of antrum and corpus, were found in 1/13 patients with RA, in 3/11 with other rheumatic diseases and 2/12 with chronic non rheumatic diseases (NS). The frequency of low serum PgA levels was no different between patients on NSAIDs 17/355 (4.8%) and those without NSAIDs 19/502 (3.8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495257 TI - Comparison of pyritinol and auranofin in the treatment of rheumatoid arthritis. The European Multicentre Study Group. AB - The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31%) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups. PMID- 8495258 TI - Efficacy and safety of radiation synovectomy with Yttrium-90: a retrospective long-term analysis of 164 applications in 82 patients. AB - In this long term retrospective study of radiation synovectomy with Yttrium-90 (Y90), we evaluated the results of 164 applications in 82 patients with RA, OA with synovitis, ankylosing spondylitis and psoriatic arthritis. Radiation synovectomy with Y90 has an overall success rate of approximately 50% and is therefore an effective alternative to surgical synovectomy in chronic synovitis which fails to respond to conservative treatment. Elbow and knee responded significantly better than shoulder and ankle joints. Patients with radiological stages from 0 to 2 showed a significantly better success rate than those with stage 3 changes. In responders, repeat therapy for recurrence of symptoms or treatment of a symptomatic corresponding symmetrical joint is advisable. Repeat therapy in a previous non-responder is associated with an unacceptably high failure rate. Therefore, when a joint fails to respond after 6 months, arthroscopy should be performed to evaluate further treatment procedures. A successful result was found in only 11 of 25 joints treated with arthroscopic synovectomy followed by radiation synovectomy within 2 weeks, indicating no benefit of this combination. PMID- 8495259 TI - Bone metabolism in rheumatoid arthritis; relation to disease activity. AB - Biochemical parameters of bone metabolism were investigated in 105 ambulant, non steroid treated patients with RA and compared with parameters of disease activity. Urinary calcium (Ca) and hydroxyproline (OHP) excretions, as parameters of bone resorption and serum alkaline phosphatase (AP), as a parameter of bone formation, were positively related to parameters of disease activity. Serum osteocalcin, another parameter of bone formation, was not related to parameters of disease activity. Patients with active disease (ESR > or = 28 mm and Ritchie articular index > or = 8) had a significant higher urinary Ca and OHP excretion (62 and 42% higher, respectively) than patients with inactive disease. Serum AP and OC were slightly higher (19 and 16%, respectively) in patients with active disease. These results suggest that in RA patients bone metabolism is related to disease activity. In active disease bone resorption seems to be increased more than bone formation, suggesting that prolonged disease activity may contribute to generalized and/or localized osteopenia. PMID- 8495260 TI - The effect of a long-term exercise programme on the rheumatoid hand. AB - Forty-four female patients with sero-positive active RA participated in a 48 month trial to assess the effect of simple hand exercises. Twenty-two patients in the test group were given a daily exercise regime of six exercises. The control group were not given any exercises. At the end of 48 months there was a statistically significant improvement in grip strength (P < 0.0001) and pincer grip strength (P < 0.0005) in the test group. There was a significant deterioration in the control group (P < 0.0000). A simple exercise programme is beneficial for the rheumatoid hand as far as grip and pincer grip strength are concerned. PMID- 8495261 TI - The molecular basis of the SSA/Ro antigens and the clinical significance of their autoantibodies. AB - The SSA/Ro antigens are nuclear and cytoplasmic polypeptides which serve as autoantigens in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). They contain two major isoforms of 60 and 52 kD. The former is the native antigen while the latter is a major autoantigen in its denatured form. A third protein of 46 kD termed 'calreticulin-Ro' is an autoantigen found in the sera of some patients with SLE. However, it is probably unrelated to the SSA/Ro system. The clinical relevance of anti SSA/Ro antibodies in rheumatic diseases has also been considered. Initially these antibodies were thought to be an epiphenomenon of autoimmune diseases. Recent studies have shown that they are associated with specific clinical manifestations and disease subsets. Furthermore, animal models have demonstrated that they may enhance tissue damage. It seems that anti-SSA/Ro antibodies may play a role in the pathogenicity of SLE and SS. PMID- 8495262 TI - Arthro-osteitis--a clinical spectrum. AB - Arthro-osteitis is an uncommon condition which can be associated with palmoplantar pustulosis. It forms part of a group of conditions which include the synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO) and sternocostoclavicular hyperostosis. We report four cases illustrating the clinical spectrum of this condition which occurred in the absence of concomitant skin lesions. One patient had extensive aortic calcification a feature not previously reported in this condition, which may represent a low grade inflammatory aortitis. PMID- 8495263 TI - Anterior mediastinal fibrosis with superior vena caval obstruction complicating the synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome. AB - A syndrome of predominantly palmo-plantar pustular psoriasis associated with anterior chest wall (sternoclavicular, manubriosternal) inflammation has previously been described. In this case, a further patient is reported where chest wall involvement is complicated by anterior mediastinal fibrosis and superior vena caval obstruction. PMID- 8495264 TI - Rheumatic fever in the pre-war years in Great Britain. PMID- 8495265 TI - Childhood arthritis: the name game. PMID- 8495266 TI - Second workshop on physiotherapy in JCA Garmisch-Partenkirchen. PMID- 8495267 TI - Study of antibodies to histones and histone synthetic peptides in pauciarticular juvenile chronic arthritis. AB - The objective of this study was to determine the prevalence of histone antibodies in early onset pauciarticular juvenile chronic arthritis (JCA), and to assess any association with disease activity in terms of arthritis or uveitis. Forty-four children with early onset pauciarticular JCA have been assessed prospectively using clinical and laboratory parameters. Sera were collected from these patients during clinical follow-up. Some of them had serial measurements during the period of study. Patient sera were analysed for histone antibodies by ELISA. A further study using 30 synthetic peptides of calf thymus core histones was performed by ELISA. Seventy-five per cent of children have IgM antibodies to histone, usually to more than one type. The highest values were anti H3 and H4 antibodies. There was no correlation between the level of anti-histone antibodies and anterior uveitis. There were increased levels of IgG antibodies to histone peptides, in particular the N- and C-terminal peptides of H3 in 70.5% of children. Antibodies to H3 peptides tend to be in patients with chronic anterior uveitis (P = 0.04). PMID- 8495268 TI - Leucopenia--an unusual presenting feature in primary systemic vasculitis. PMID- 8495269 TI - Steroid treatment in giant cell arteritis. PMID- 8495270 TI - Tropical pyomyositis in a temperate climate. PMID- 8495271 TI - Relapsing eosinophilic myositis causing acute muscle compartment syndrome. PMID- 8495272 TI - Upper gastrointestinal complaints and complications in chronic rheumatic patients in comparison with other chronic diseases. PMID- 8495274 TI - Cyclosporin A in adult dermatomyositis. PMID- 8495273 TI - A case of reactive arthritis following exposure to industrial gases and oils. PMID- 8495275 TI - Differential effect of glucocorticoids on calcium absorption and bone mass. AB - Osteoporosis is one of the most serious side effects of glucocorticoid therapy and its development and severity are dependent on the particular glucocorticoid used. A short-term study (15 days) comparing the bone wasting effects and changes in calcium absorption induced by equiactive low and high doses of prednisone, deflazacort (DFZ) and betamethasone, revealed that low and high doses of betamethasone and high doses of prednisone induced a significant decrease in intestinal calcium absorption. No such changes were observed with DFZ. As 1,25 dihydroxycholecalciferol levels were maintained throughout the study, it appears that glucocorticoids impair calcium absorption through a mechanism not involving this hormone. A long-term study (1 year) of equipotent doses showed that all three glucocorticoids caused a decrease in calcium absorption and a progressive decrease in lumbar spine bone mineral content. However, the impairment of calcium absorption and decrease in bone mineral content was least with DFZ. Thus, DFZ appears to offer a degree of protection against both decreased calcium absorption and bone loss. PMID- 8495276 TI - Potency ratio--a brief synopsis. AB - Deflazacort (DFZ) is a novel glucocorticoid with bone sparing properties, and there have been numerous studies investigating its potency relative to other glucocorticoids. As estimates of potency are difficult to evaluate in patients with disease, the concept of minimum effective dose is used. In double-blind, crossover studies, paired patient studies and between-patient studies, the potency of DFZ to prednisone (PDN) and to methylprednisolone was established as being 1.28:1 (1.17-1.38, 95% CI) and 1.6:1 (1.45-1.75, 95% CI), respectively. The bone wasting properties of DFZ have been determined using the concept of bone wasting ratio (ratio between bone loss velocity values observed in patients given the minimum effective doses of two glucocorticoids). The results of three studies which have evaluated the bone wasting ratio of PDN to DFZ indicate that this ratio is approximately 2.03:1 (1.84-2.23, 95% CI). That is, at therapeutically equivalent doses, twice as much bone loss occurs with PDN as with DFZ. PMID- 8495277 TI - Glucocorticoid effects on statural growth. AB - Glucocorticoid use in children is not only associated with the side effects which are seen in adults, but also with severe adverse effects on statural growth. As little as 2.5-5.0 mg prednisolone/day can cause a retardation in statural growth. A direct relationship exists between the dose of glucocorticoid used and statural growth. The use of knemometry, a sensitive technique for measuring the growth of long bones in children has increased the accuracy of growth rate measurements. Many factors, such as disease process, sex, daily vs alternate day therapy, ethnic variations or whether the patient has been immobilized must be considered when evaluating the effects on stature of a particular glucocorticoid. Although alternate day therapy may benefit some patients (particularly those with juvenile chronic arthritis), not all patients respond beneficially to this type of regimen. New generations of glucocorticoids which may not be as detrimental to the growing child should now be considered. PMID- 8495278 TI - Some molecular mechanisms of glucocorticoid action. AB - Glucocorticoids, in excess, profoundly affect the skeleton by increasing bone resorption, decreasing bone formation and altering intestinal absorption and renal excretion of mineral ions. The mechanisms underlying these actions are complex but many involve changes in expression of genes encoding critical proteins. Interaction of the glucocorticoid with its nuclear receptor results in the induction of either positive events (transactivation) by direct interaction with cis-acting sequences, or negative (transrepression) events by repression of gene transcription and/or alteration of mRNA half-lives. An example is the inhibition by glucocorticoids of collagenase synthesis. Induction of the collagenase (procollagenase) gene by inflammatory mediators, such as interleukin 1, can be inhibited by glucocorticoid transrepression. The glucocorticoid receptor complex binds to a protein complex AP-1; consisting of the proteins c JUN and c-FOS) and prevents this complex from inducing activation of the procollagenase gene. These observations may be applicable to the interpretation of other glucocorticoid actions and explain some of their adverse effects on the skeleton. PMID- 8495279 TI - Dose-dependent effects of deflazacort and prednisone on growth and skeletal maturation. AB - Deflazacort (DFZ), a new glucocorticoid which has recently become available, is expected to have less negative effects on growth and skeletal maturation than conventional steroids, in children treated long term. To verify this hypothesis, a multicentre trial was organized to evaluate the effects of DFZ vs prednisone (PDN) on statural growth and skeletal maturation in a group of prepubertal children requiring glucocorticoid therapy for at least 6 months/year. The results of an analysis of 55 children (aged 3-12 years, 24 with connective tissue disease and 31 with kidney glomerular disorders) treated randomly with either DFZ (31 patients) or PDN (24 patients) and followed for a mean period of about 22 months (16 months under steroid therapy) are presented. The observation period was split up into the following phases according to dose and administration regimen: daily, high-dose therapy; alternate-day, high-dose therapy; low-dose therapy; suspension of treatment. The height, statural age, skeletal age and body weight velocities (i.e. the increase/year) were considered. In spite of large intra-individual and inter-individual variability, the results suggest that DFZ has a lower negative impact on indicators of growth. During high-dose daily administration, the height velocity tended to be lower in the PDN group and the impairment of skeletal maturity was significantly less for DFZ than for PDN. During an alternate-day regimen, height velocity was slightly higher in the PDN group and skeletal age velocity was higher in the DFZ group. It seems that steroid effects on statural growth and bone maturation occur in parallel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495280 TI - Cellular regulatory mechanisms that may underlie the effects of corticosteroids on bone. AB - The overall effects of corticosteroids on the skeleton are dependent on many factors including dose, duration of exposure to the steroid, steroid type and species. Some effects are indirect and are brought about by changes in, for example, parathyroid hormone secretion and intestinal calcium absorption, while others may result from cellular responses within the microenvironment of bone itself. Explants of trabecular bone are commonly used to study glucocorticoid effects in vitro, though it is often difficult to be certain that in vitro results directly reflect in vivo activity. Corticosteroids are dual inhibitors of cyclo-oxygenase and lipo-oxygenase, and may exert effects via inhibition of eicosanoid synthesis. They can also inhibit synthesis of cytokines, such as interleukin-1, which stimulate bone resorption and remodelling, by monocytes and macrophages. The production of cytokines and growth factors by bone cells themselves and the expression of their receptors may also be influenced by corticosteroids. Examples of corticosteroid-induced inhibition of synthesis include tumour necrosis factor and interleukin-6, and such effects may be important in explaining therapeutic actions of corticosteroids (e.g. in myeloma). Although it is not yet clear why different glucocorticoids have different effects, a number of factors determine the overall effect of a steroid. These include steroid metabolism and tissue distribution, selective effects on cytokine production, and tissue differences in gene transcription. PMID- 8495281 TI - BIR presidential address: exploring the niches. AB - In his 1990 Presidential Address Professor C R Hill posed the question of whether, given the ethos of the late 20th century, there was a future for radiological science. To answer his question he reviewed the scientific basis of current major branches of radiology, demonstrating progress resulting from initial physical discovery, combined with engineering and medical inventiveness. In the process of the development of radiological science, small-scale speculative research, outside mainstream areas, has proved to be an important element. This address complements Professor Hill's by examining the role of a small-scale speculative research (the niches of the field). Examples are taken from the early pioneers of radiological science and the first British Institute of Radiology Congress. Finally some lesser known research activity in this category, being presented at the Golden Jubilee Congress, is reviewed. PMID- 8495282 TI - Review article: MRI of the knee. AB - The inherent vulnerability of the knee to injury and degenerative change means that there is a major requirement for an imaging technique capable of assessing such damage accurately, rapidly and non-invasively. Over a relatively short time magnetic resonance imaging (MRI) has emerged as the technique of choice in the assessment of internal derangement of the knee. The present review describes the wide application of MRI to the knee and considers the position of MRI in relation to other diagnostic methods. PMID- 8495283 TI - Total body studies in normal British women using dual energy X-ray absorptiometry. AB - We report dual energy X-ray absorptiometry (DXA) studies of total body bone mineral and body composition performed in 111 normal caucasian women (aged 42 61). Conventional DXA scans of the lumbar spine and femoral neck were also obtained and each woman completed a detailed questionnaire. Significant correlations were found between total body BMD and BMD in the lumbar spine (r = 0.76) and femoral neck (r = 0.72). We present reference range data for BMD in the total body and in seven subregions of the skeleton. Multiple linear regressions of total body BMD and BMC on weight, height and age showed that the inclusion of height compared with weight and age alone was not statistically significant. The dependence of total body BMD on weight and age was: total body BMD (g cm-2) = 1.043 + 0.0042 x weight (kg) - 0.0039 x age (years) (R = 0.46, SEE = 0.074 g cm2). Body mass derived from DXA scans correlated well with weight measured on scales (r = 0.996, SEE = 0.77 kg). Body composition measurements agreed closely with % body fat estimated from skinfold measurements (r = 0.93), body fat mass estimated from a predictive equation based on weight, height and age (r = 0.91) and % body fat estimated from a predictive equation based on body mass index (r = 0.76). Study precision gave coefficients of variation of 0.6% for total body BMD and 0.7% for % body fat. PMID- 8495284 TI - Accuracy of lateral dual energy X-ray absorptiometry for the determination of bone mineral content in the thoracic and lumbar spine: an in vitro study. AB - Lateral scanning with dual energy X-ray absorptiometry (DXA) was undertaken on 153 thoracic and lumbar vertebral bodies from nine individuals (mean age 67; range 34-92 years) to establish their bone mineral content (BMC). All specimens were subsequently de-fatted and ashed to compare ash weight with BMC of the T1 to L5 segments. Linear regression analysis indicated a higher correlation between BMC and measured ash weights for each vertebral column (range: r = 0.97-0.99), with error for all vertebrae tested showing a standard error of 0.40 g, or 10.8%. For the L2-4 segments the accuracy error was 0.50 g or 7.9%. In both cases there was a mean trend towards underestimation of ash weight. Mean BMC values of the T1 to T5 segments were similar before a progressive increase caudally. These data affirm the utility of DXA for determining bone mineral content in the vertebral column across wide ranges of age, and segmental and bone density. PMID- 8495285 TI - In search of optimum chest radiography techniques. AB - A nation-wide study of chest radiography in Sweden had previously revealed a large variation in the physical and technical factors involved, in particular the radiation dose. In this study the image quality could not be assessed unambiguously. The aim of the present study was to try to establish a correlation between visual grading of radiographs and physical and technical factors in order to find the optimum chest X-ray system. The physical and technical performance of 24 chest units was evaluated. Radiographs were taken of an anthropomorphic chest phantom supplied with test structures simulating various pathologies. Image quality was assessed by visual grading analysis of the radiographs. The physical and technical parameters of the units rated best were used to exemplify good radiographic practice. The results were in agreement with the recommendations issued by the Commission of the European Communities (CEC). It was also shown that low radiation dose is compatible with high-quality radiographic imaging of the chest. PMID- 8495286 TI - Oesophageal varices: how reliable is a barium swallow? AB - Although barium swallow is a quick and easy method for diagnosing oesophageal varices, there is considerable variation between observers because objective quantitative radiological criteria have so far not been defined. In order to define these criteria, a blind radiological/endoscopic comparative study using endoscopy as the gold standard was retrospectively carried out in 72 patients. A prospective study was then carried out in 47 patients to define the validity of the radiological criteria found by the first study. The results of both studies showed that the length and the width of the mucosal folds representing varices as measured on barium swallow radiographs have a significant relationship with the grade of the varices as determined by endoscopy. We conclude that barium swallow is a quick and reliable method for quantitative assessment of oesophageal varices. PMID- 8495287 TI - Coronary angiography: an analysis of radiographic practice in the UK. AB - There is growing public and professional concern over the risks of medical ionizing radiation. It is therefore important to examine our procedures for ways in which we can reduce radiation dose to patients and staff. We surveyed 48 catheter laboratories nationwide to establish the range of practice in performing "routine" coronary angiography and left ventriculography. There were wide variations in the numbers of views obtained, mean cine film lengths and mean fluoroscopy times. Despite the recommendation of the National Radiological Protection Board, only five of the 36 centres responding were able to provide estimates of patient radiation dose per procedure. Calculations of maximum and minimum patient doses, based on cine film length and fluoroscopy time, show a fourfold variation between hospitals. Using the concept of estimated dose equivalent, the predicted lifetime fatal cancer risk for a routine examination ranges from 1/16,600 to 1/4300. As a preliminary step in radiation dose reduction we have used this survey data to suggest how a typical coronary angiogram and left ventriculogram might be performed. PMID- 8495288 TI - Physical aspects of photostimulable phosphor computed radiography. AB - Currently photostimulable phosphor computed radiography (PPCR) promises to be the digital X-ray image acquisition technology of choice for classical radiography (i.e. X-ray examinations of natural anatomy). For the last two years we have been carrying out a physical evaluation of modern PPCR technology and some of our findings relevant to general radiographic applications are reviewed here. Topics covered include the function of the auto-reader system and the reliability of image reproduction, the radiation exposure requirement and physical image quality. The latter is based upon both objective and subjective measures of image quality. These studies have yielded a favourable comparison of the image quality of modern PPCR technology with that of medium-speed and fast radiographic screen film combinations. The major advantages of PPCR appear to be the maintenance of high imaging efficiency (DQE) over a much wider range of signal levels than film and consistent image acquisition and presentation independent of exposure level. In general radiographic applications no major limitations due to the comparatively modest limiting spatial resolution of PPCR [maximum limiting resolution = 5 line-pair mm-1] have been experienced. Digital image enhancement is a central element of PPCR image reproduction. The authors believe that advances in image enhancement algorithms remain a potential area for further improving the presented quality of PPCR images. PMID- 8495289 TI - Factors affecting the radiation dose to the lens of the eye during cardiac catheterization procedures. AB - Concern has been expressed about the relatively high radiation doses to the lens of the eye received by the operator during cardiac catheterization studies. A study was undertaken to assess the occupational doses received by cardiologists and to examine the factors that affect the individual's eye dose. Eighteen cardiologists working in five catheterization laboratories at three centres were included in the study. Their eye doses, workload and individual study details were monitored at each centre. Operating dose rates and scattered radiation were also measured for each unit to compare equipment performance. The study demonstrated that the relationships between the cardiologist's eye dose and factors such as the dose efficiency of the X-ray equipment, scattered dose rates, examination protocols and workload are complex and vary from centre to centre. Because of these variations general workload limits may be inaccurate and should only be used for general guidance when no direct measurements are available. Such limits should be verified by local measurements as soon as is practical. PMID- 8495290 TI - An optical system for measuring surface shapes for radiotherapy planning. AB - A system which uses two remote cameras to obtain surface contours for radiotherapy patients is described. Two variants are presented: one which requires couch movement to obtain multiple outlines, and one utilizing a special illumination method to achieve multiple outlines from one image per camera. In addition, a technique is discussed in which the grey-scale information from the skin surface (e.g., skin marks placed by the radiotherapist) may be utilized in displaying three-dimensional surface information. The system may also be used to monitor patient position in real time during each treatment. PMID- 8495291 TI - Technical note: a simple solution to the problems of testing automatic exposure control in diagnostic radiology. PMID- 8495292 TI - Technical note: an integrated phantom for HDR quality control. PMID- 8495293 TI - Case report: soft tissue and perivisceral calcification occurring in an infant: a case of brown fat necrosis. AB - Fat necrosis is a well described cause of widespread subcutaneous calcification occurring in a young infant. In this condition the radiographic demonstration of soft tissue calcification is often dramatic but is clinically irrelevant since the diagnosis is usually evident without recourse to radiology. Visceral fat necrosis and calcification, in the absence of hypercalcaemia, have been reported occasionally in association with subcutaneous fat necrosis. We report a case with calcification largely confined to deep perivisceral sites without clinical signs of subcutaneous fat necrosis. PMID- 8495294 TI - Case report: paediatric radiotherapy--the avoidance of late radiation damage to the growing hip. PMID- 8495295 TI - Case report: radiotherapy--an effective treatment for vaginal verrucous carcinoma. AB - Vaginal carcinoma makes up 1%-2% of all gynaecological tumours. Verrucous carcinoma of the vagina is even more rare--only 16 cases are reported in the scientific literature. A case of a complete regression after 60 Gy fractionated radiotherapy by a tumour 12 cm3 in size is reported. Most authors are of the opinion that radiotherapy causes anaplastic transformation of verrucous carcinoma. The minority view, that anaplastic transformation does not occur, is correct and is supported by our clinical and radiological data. The conflicting literature on vaginal verrucous carcinoma (VVC) is reviewed with reference to verrucous carcinoma at other sites. PMID- 8495296 TI - Case of the month: a pain in the neck. PMID- 8495297 TI - Short communication: dynamic forces influencing vertebral fracture risk. PMID- 8495298 TI - Optimization of X-ray spectra for mammography. PMID- 8495299 TI - Lymphatic fistula and perigraft seroma. PMID- 8495300 TI - Diagnostic value of cytology for biliary stricture. AB - Over the past 20 years, bile aspiration at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography has been developed for cytological diagnosis of biliary tract stricture. This safe and specific test has allowed a diagnosis to be reached before or without operation in about one-third of malignancies of the pancreas or biliary tree. The recent development of biliary brush cytology has produced better results. An endobiliary biopsy forceps is now available that may allow safe sampling of lesions causing extrinsic compression of the biliary tract. An endobiliary aspiration cytology needle has been produced that may permit non-ulcerating lesions to be diagnosed. A safe alternative to endobiliary methods is percutaneous fine-needle aspiration cytology; this yields a diagnosis in about half of patients presenting with obstructive jaundice and an imaged mass lesion. PMID- 8495301 TI - Adrenal incidentaloma. AB - Improvements in ultrasonography and computed tomography have led to the problem of 'adrenal incidentaloma', an asymptomatic adrenal mass discovered during investigation of some other problem. In the light of current knowledge a management rationale for patients with such an adrenal abnormality is proposed. PMID- 8495302 TI - Hyperaemic response in the skin microcirculation of patients with chronic venous insufficiency. AB - The capacity of the microcirculation in the liposclerotic skin of patients with chronic venous insufficiency to vasodilate in response to pilocarpine electrophoresis was assessed using laser Doppler fluxmetry. Pilocarpine induces vasodilation by direct action on capillaries; other methods of vasodilatation, such as heating of the skin, act by a number of pathways including a neurogenic one. Thirty patients with lipodermatosclerosis and chronic venous insufficiency and 20 control subjects were studied. There was no difference in peak vasodilatation following pilocarpine electrophoresis in the two groups. The median (interquartile range) peak flux in patients was 665 (382-1025) units and in controls 765 (452-975) units (95 per cent confidence interval of difference- 270 to 150 units, P = 0.5). This suggests that the capillaries in the liposclerotic skin of patients with chronic venous insufficiency have a normal capacity to vasodilate. PMID- 8495303 TI - Treatment of the axilla in patients with screen-detected breast cancer. AB - Management of the axillary lymph nodes in patients with screen-detected breast cancer is controversial. Optimal treatment should combine accurate determination of node status and avoidance of unnecessary morbidity. This study attempted to determine whether axillary node status could be accurately predicted using selected criteria in women with screen-detected breast cancer. Of 223 breast cancers excised in the Greater Manchester breast screening programme, 180 were invasive and 40 of these had associated lymph node metastases. The presence of involved nodes was associated with large tumour size, high tumour grade and the absence of mammographic microcalcification. Multiple logistic regression analysis revealed that each of these three factors was independently significant. Women with a screen-detected breast cancer < 1 cm in diameter or those with grade I tumours < 3 cm (35 per cent of the total) could be spared axillary surgery with an expected reduction in morbidity and operating time. PMID- 8495304 TI - Symptomatic outcome after laparoscopic cholecystectomy. AB - To evaluate the symptomatic outcome after laparoscopic cholecystectomy, a standard symptom questionnaire was sent to three patient groups at least 1 year after surgery: 115 patients had undergone laparoscopic cholecystectomy; 200 had undergone open cholecystectomy; and 200 had had inguinal hernia repair. Return of questionnaires was higher after laparoscopic cholecystectomy (100 of 115; 87.0 per cent) than the open procedure (167 of 200; 83.5 per cent) or hernia repair (163 of 200; 81.5 per cent). There was no difference in the number of patients who considered the operation to have cured or improved their preoperative symptoms after laparoscopic cholecystectomy (94 of 100; 94.0 per cent), open cholecystectomy (157 of 167; 94.0 per cent) or hernia repair (154 of 163; 94.5 per cent). Similar numbers considered their operation to have been a success (94.0, 95.2 and 94.5 per cent respectively). The prevalence of abdominal pain, nausea, flatulence, food intolerance and heartburn was similar in all groups of patients following operation. Diarrhoea occurred more often following laparoscopic (6.0 per cent) and open (4.2 per cent) cholecystectomy than hernia repair (1.2 per cent). Patients who underwent laparoscopic cholecystectomy tended to have a higher incidence of nausea or vomiting than those undergoing the open procedure, and consumed significantly more antacids (23.0 versus 12.0 per cent, P < 0.02). Laparoscopic cholecystectomy achieved the same rate of patient satisfaction as open cholecystectomy, with no apparent symptomatic advantage. PMID- 8495305 TI - Expression of p53 in colorectal cancer and dysplasia complicating ulcerative colitis. AB - An immunohistochemical method using Pab1801, a monoclonal antibody specific to the human p53 protein, was applied to detect p53 expression in colorectal cancer and dysplasia complicating ulcerative colitis. Of 20 tissue samples with dysplasia, six showed positive immunoreactivity. Archival paraffin-embedded tissue blocks from 21 colitic cancers were analysed; 11 showed positive immunoreactivity, compared with ten of 21 samples from matched sporadic colorectal cancers (P not significant). Previous data suggesting that colorectal carcinoma complicating ulcerative colitis has a reduced frequency of c-Ki-ras mutation compared with sporadic cancer have led to the hypothesis that different genetic lesions underlie colitic and sporadic colorectal carcinoma. The present results suggest that this is not the case with regard to p53 gene alterations. PMID- 8495306 TI - New technique to measure mucosal metabolism and its use to map substrate utilization in the healthy human large bowel. AB - A new method of assessing substrate utilization in gastrointestinal mucosal specimens is described. Small human endoscopic biopsy specimens with wet weights ranging between 1.4 and 12.2 mg were used to quantify the oxidation of three metabolic substrates, glucose, glutamine and butyrate, through to carbon dioxide over a 2-h period. The technique proved to be reproducible and capable of distinguishing variations in mucosal metabolism between individuals (P < 0.0001 for each substrate). Results were similar to those obtained previously using human and rat colonocytes. To characterize the metabolism of the healthy large bowel, specimens were obtained from five regions in 15 patients who had a normal colonoscopic examination. The results show that butyrate is the preferred fuel source of large bowel mucosa, followed by glutamine, then glucose (P < 0.01). There was no significant regional variation in utilization of the three substrates between the five regions; with respect to glutamine, this is contrary to previous findings. PMID- 8495307 TI - Abdominal aortic aneurysm: still missing the message. AB - Over a 7-month period 50 patients presented to the vascular unit with a ruptured or acute symptomatic abdominal aortic aneurysm (AAA). Information regarding the 24 months before acute presentation was obtained from the patient, family doctor and relevant case records to determine whether an asymptomatic aneurysm had previously been diagnosed but the patient not referred to the vascular service, or whether the patient had undergone an examination at which an aneurysm might reasonably have been expected to be diagnosed. Thirteen patients (26 per cent) had previously had an AAA diagnosed but only five had been referred. Thirteen patients (26 per cent) had had a total of 16 inpatient hospital admissions without an asymptomatic aneurysm being diagnosed. Six patients (12 per cent) underwent abdominal examination for an unrelated complaint by the family doctor without an asymptomatic aneurysm being diagnosed. A significant impact on overall mortality from aortic aneurysm may be made by increasing the number of patients undergoing elective aneurysm repair. All doctors should assess aortic diameter in all patients over 50 years of age who undergo abdominal examination for whatever reason. All patients diagnosed as having an asymptomatic AAA should be referred to a vascular surgeon for assessment. PMID- 8495308 TI - Reoperation for suspected primary hyperparathyroidism. AB - A retrospective analysis of 93 patients undergoing 128 re-explorations for persistent or recurrent hypercalcaemia is presented. Seventy-six patients (82 per cent) became normocalcaemic after between one and five reoperations. Nine patients had hypercalcaemia caused by sarcoidosis, familial hypocalciuric hypercalcaemia or metastatic disease, and two had parathyroid carcinoma. Fifteen patients (16 per cent) developed permanent hypoparathyroidism requiring vitamin D and/or calcium therapy and nine had permanent recurrent laryngeal nerve paralysis. Undetected adenomas (41 cases) and inadequate resection in hyperplastic disease (28) were the predominant causes of initial failure. Reoperation for persistent or recurrent hyperparathyroidism restored normocalcaemia in the majority of patients. This 'cure' was achieved at the cost of considerable morbidity and a careful risk-benefit analysis of each patient is recommended before performing reoperative parathyroid surgery. PMID- 8495309 TI - Fungating benign ductal adenoma of the breast. PMID- 8495310 TI - Intraoperative assessment of nodal status in the selection of patients with breast cancer for axillary clearance. AB - Preliminary axillary node sampling with intraoperative reporting of imprint cytology to detect positive nodes was assessed in 50 consecutive patients with T1 or T2 breast cancer undergoing axillary clearance, 21 of whom were histologically node positive. A mean of 3.5 (range 1-4) nodes were sampled. Axillary clearance yielded a mean of 11.7 (range 4-32) nodes. Of node-positive patients, sampled nodes detected 18 of 21 on immediate processing, one on subsequent paraffin sections, and failed to detect two (one of ten and one of 17 positive nodes). If the technique had been used during operation to select patients for axillary clearance, 29 of 50 would have avoided the operation, one of two node-positive patients would have required delayed axillary treatment and two of 21 with minimal axillary disease would not have received further axillary treatment or adjuvant therapy. The technique may be useful in reducing the morbidity of breast cancer surgery without increasing the risk of locoregional or distant recurrence. PMID- 8495311 TI - Antibiotic prophylaxis is indicated for chest stab wounds requiring closed tube thoracostomy. AB - To determine the role of antibiotic prophylaxis for stab wounds of the chest requiring intercostal tube drainage, a double-blind study was conducted comparing cefazolin, given to 57 patients at 500 mg every 8 h for 24 h, with placebo, given to 56. Differences were detected in the rate of thoracotomy for sepsis (antibiotic nil versus placebo 9 per cent, P < 0.05) and in the frequency of sputa positive for pathogens (12 versus 34 per cent respectively, P < 0.05), but the incidence of pyrexia, raised white cell count, positive cultures from pleural drainage or intercostal catheter tips and volume of chest drainage was similar. The mean hospital stay and costs consequent on morbidity were greater in patients receiving placebo, supporting the conclusion that antibiotic prophylaxis is indicated. PMID- 8495312 TI - Protein C deficiency and rapidly progressing peripheral arterial disease. PMID- 8495313 TI - Role of reflux oesophagitis and acid in the development of columnar epithelium in the rat oesophagus. AB - The role of reflux oesophagitis and acid in the development of oesophageal columnar epithelium was investigated in the rat. Twenty-four animals underwent total gastrectomy and oesophagojejunostomy, inducing reflux of duodenal contents into the oesophagus, and were divided into two groups: an 'acid' group, which drank syrup water with hydrochloric acid (pH 1.8), and a 'non-acid' group, which drank only syrup water (pH 6.5). Four rats were killed at 4, 8 and 12 weeks after surgery. Reflux oesophagitis was found in the lower portion of the oesophagus in all cases. Columnar epithelium was observed in the oesophagus of one rat in the non-acid group at week 8 and of three in the acid group at week 12. These results indicate that the development of columnar epithelium of the oesophagus is preceded by reflux oesophagitis and that acidic conditions may promote this change. Columnar epithelialization may result from metaplasia of squamous epithelium as well as from upward extension of columnar epithelium. PMID- 8495314 TI - Incidence and management of benign anastomotic stricture after cervical oesophagogastrostomy. AB - Benign anastomotic stricture after transhiatal oesophagectomy and gastric tube reconstruction constitutes a major problem. From August 1988 to April 1991, 81 patients were followed after cervical oesophagogastrostomy. Twenty-four patients (30 per cent) developed a benign anastomotic stricture 3-23 (median 8) weeks after operation. Poor vascularization of the gastric tube, determined during operation, and postoperative anastomotic leakage were statistically significant risk factors for stricture formation. Symptoms related to stricture were often typical and were confirmed by endoscopy and/or radiography. Radiography did not yield information additional to that obtained from endoscopy. Strictures were treated in the outpatient clinic by dilatation with Savary dilators. Repeated dilatation completely alleviated dysphagia in 20 of the 24 patients (83 per cent). In ten patients dilatations could be discontinued after a median of 8 (range 1-17) sessions. Dilatation was continued until the end of follow-up in nine patients or until death from recurrent disease in five. No complications of dilatation were seen. PMID- 8495315 TI - Norwegian multicentre study of survival and prognostic factors in patients undergoing curative resection for gastric carcinoma. The Norwegian Stomach Cancer Trial. AB - The influence of clinical and tumour-related variables on long-term survival in patients with gastric carcinoma was studied in a national prospective multicentre study. A total of 532 patients underwent curative surgery with a 5-year survival rate of 40 per cent. In a Cox multivariate analysis, age, stage of disease and macroscopic appearance of tumour were the only factors that independently affected survival. The estimated probability of survival to 5 years for a 50-year old patient with a flattened tumour type and stage I disease was 71 per cent, but 50 per cent for an 80-year-old with the same tumour type and stage. For stage II disease the rates were 56 and 32 per cent, for stage III 39 and 13 per cent and for stage IV 19 and 3 per cent, respectively. A 70-year-old patient with stage II linitis plastica tumour type had an estimated probability of 5-year survival of 20 per cent. Stage of disease was the single most important factor in determining survival. Lauren histopathological type and location of tumour, Karnofsky performance index, weight loss and type of resection had no significant effect on long-term survival. PMID- 8495316 TI - Vagal system involvement in changes in small bowel motility during restraint stress: an experimental study in the dog. AB - Changes in small intestinal motility were studied during restraint stress in fasting animals and after food; the involvement of the vagal system in the pathophysiology of these changes was assessed. Small intestinal motility was recorded in 40 dogs using electromyography with monopolar electrodes and manometry with submucosal microballoons. Twenty animals underwent bilateral truncal vagotomy. Stress increased intestinal motility (percentage of slow waves followed by action potentials in 1 min), both in fasting conditions (P < 0.001) and post-prandially (P < 0.001). It also completely abolished the migrating motor complex-interdigestive myoelectric complex periodicity characteristic of the normal fasting pattern. In dogs subjected to vagotomy, restraint stress increased motility during fasting (P < 0.001) but decreased it after feeding (P < 0.01). Restraint stress thus increases small intestinal motility, both during fasting and after food. The vagal system is partially involved in this hypermotility response. PMID- 8495317 TI - Obesity: an important prognostic factor in acute pancreatitis. AB - Ninety-nine patients with acute pancreatitis in whom body mass index (BMI = weight (kg)/height2 (m2)) was measured were studied prospectively to determine the importance of obesity as a prognostic factor in this disease. Of 19 obese patients (BMI > or = 30 kg/m2), 12 developed severe pancreatitis; seven had abscesses, of whom five died, and two further patients died. In 80 non-obese patients, the incidence of severe pancreatitis (n = 5), abscess formation (n = 4) and death (n = 4) was significantly less (P = 0.0007). The mean(s.d.) BMI of 17 patients with severe acute pancreatitis was significantly higher than that in 82 patients with mild acute disease (31.2(5.6) versus 23.3(5.6) kg/m2, P < 0.001). As a single prognostic factor, obesity had a sensitivity of 63 per cent and a specificity of 95 per cent for predicting disease severity. When five obese women with gallstone pancreatitis were excluded, the sensitivity of obesity increased to 86 per cent. Severe pancreatitis occurred in all eight obese patients with disease of an alcoholic aetiology. These data suggest that increased fat deposits in the peripancreatic and retroperitoneal spaces in obese patients may increase the risk of peripancreatic fat necrosis, abscess and death. Consideration should be given to including obesity as a prognostic factor in acute pancreatitis. PMID- 8495318 TI - Hereditary calcific pancreatitis in an English family. PMID- 8495319 TI - Intraluminal duodenal diverticulum: an unusual cause of acute pancreatitis. PMID- 8495320 TI - Graft size assessment by preoperative computed tomography in living related partial liver transplantation. AB - The size of segmental liver grafts assessed by preoperative computed tomography (CT) volumetry was evaluated in relation to surgical outcome in 14 living related partial liver transplantations (LRLTs). The aim was to show that graft size can be accurately assessed before operation and to estimate the lower safety limit of graft size in assessing subsequent graft function and survival. The relationship between calculated CT volume and weight of the liver was linear in the recipient (r = 0.97) and donor (r = 0.98). The mean(s.e.m.) modified liver weight ratio (MLWR; ratio of graft weight to recipient's expected liver weight based on body weight) was 0.59(0.07) (range 0.27-1.09). Surgical complications related to an oversized graft and primary graft failure caused by a small-for-size graft were not observed. The lowest MLWR of any survivor was 0.27. These results suggest that a partial liver graft reduced to about 30 per cent of the recipient's expected liver weight can tolerate LRLT well. PMID- 8495321 TI - Changes in liver blood flow associated with the growth of hepatic LV10 and MC28 sarcomas in rats. AB - Abnormalities in liver blood flow are known to occur in patients and animals with overt hepatic tumour. This study investigated the changes in liver blood flow associated with the development of overt hepatic tumour in two different models. Hepatic tumour was induced by intraportal inoculation of either 300 LV10 sarcoma cells or 10(5) MC28 sarcoma cells in rats. Liver blood flow and hepatic haemodynamics were measured 3 weeks later when overt liver tumour was present. The hepatic perfusion index (HPI), the ratio of hepatic arterial to total liver blood flow, was raised and portal venous inflow reduced in rats with LV10 tumours, but not in those with MC28 lesions. Hepatic arterial flow was unchanged in LV10 tumours when the HPI was raised and neither model demonstrated arteriosystemic or portosystemic shunting. The changes in portal venous inflow were associated with a significant increase in portal and splanchnic vascular resistance. These studies suggest that liver blood flow changes in the presence of overt hepatic tumour are not related to portal venous obstruction but may be caused by a circulating splanchnic vasoconstrictor. PMID- 8495322 TI - Carcinoid tumours of the appendix in children 1957-1986: incidence, treatment and outcome. AB - Forty carcinoid tumours of the appendix were identified in children under 15 years of age between 1957 and 1986 from the records of the West Midlands Regional Children's Tumour Research Group. A significant excess of girls was observed (P = 0.02). All tumours were discovered incidentally and two patients underwent further surgery. Twenty-two of the 29 confirmed locations (76 per cent) were at the tip of the appendix and 34 of the 40 tumours (85 per cent) had invaded beyond the appendiceal submucosa. The reported incidence rate of 1.14 per million children per year remained constant throughout the study period. No recurrences, metastases or deaths from tumour were detected. Appendicectomy alone is confirmed as usually curative, although right hemicolectomy is occasionally necessary. Caution during routine appendicectomy is recommended to avoid possible tumour damage, as is consistent histological examination of all appendices in the paediatric age group. The importance of long-term follow-up is emphasized. PMID- 8495323 TI - Treatment of perforated sigmoid diverticulitis: a prospective randomized trial. AB - A prospective randomized trial was carried out on 62 patients with diffuse peritonitis from perforated diverticulitis of the left colon, comparing acute transverse colostomy, suture and omental covering of a visible perforation with acute resection without primary anastomosis. For purulent peritonitis the postoperative mortality rate was significantly higher after acute resection (six of 25) than after colostomy (none of 21). In those treated by acute resection, the mortality rate was not significantly higher after Hartmann's procedure (five of 15) than after exteriorization of both lumens (one of ten). The postoperative mortality rate in patients with faecal peritonitis did not differ significantly between colostomy (six of ten) and acute resection (two of six). Stomas became permanent in four of 25 patients with diverticulitis surviving acute colostomy and in seven of 22 surviving acute resection. Suture and transverse colostomy is superior to resection for purulent peritonitis because of the lower postoperative mortality rate and in spite of the shorter hospital stay in those surviving acute resection. PMID- 8495324 TI - Anal endosonography and correlation with in vitro and in vivo anatomy. AB - The endosonographic anatomy of the anal sphincters was studied by in vivo and in vitro correlation with anatomical dissection. Fourteen fresh anorectal specimens (eight abdominoperineal resection, six post mortem) were scanned in a water-bath with sequential dissection and correlation with the ultrasonographic images. Accurate anatomical identification of the layers during dissection was confirmed histologically. Anal endosonography was performed during operation in 12 patients to validate the in vitro findings. The in vivo study confirmed the in vitro results. Basic endosonographic anatomy has been clarified and inaccuracies in the previous description of the longitudinal muscle and external anal sphincter corrected. PMID- 8495325 TI - Colonic bacteria and bacterial translocation in experimental colitis. AB - The indigenous intestinal flora and an intact mucosa are vital components of body defences against luminal pathogenic bacteria. Disruption of these defences in inflammatory bowel disease may permit bacterial translocation and contribute to disease severity. Support for this hypothesis comes from this study of a hapten induced rat model of colitis. Induction of colitis was associated with a significantly increased colonic Gram-negative aerobic bacilli count. The results, expressed as log10 [colony-forming units per gram tissue] were: colitic 6.97-8.86 versus control 4.90-6.69 (P < 0.05). Colitis was also associated with a decreased Gram-positive cocci count at 4.00-8.04 versus control 6.45-8.30 (P < 0.05). Bacteria translocated to the mesenteric lymph nodes in five of eight colitic rats (P = 0.01), to the spleen in four (P = 0.04) and to the liver in five (P = 0.01) but to these organs in none of the eight control animals. There was a positive correlation between the severity of colonic inflammation and extent of bacterial translocation in colitic animals (rs = 0.86, P = 0.007). PMID- 8495326 TI - Intraoperative irrigation for acute distal colonic obstruction caused by carcinoma. PMID- 8495327 TI - Laparoscopic repair of perforated peptic ulcer. PMID- 8495328 TI - Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia. PMID- 8495329 TI - Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia. PMID- 8495330 TI - Non-steroidal anti-inflammatory drugs and appendicitis in patients aged over 50 years. PMID- 8495331 TI - Laparoscopic herniorrhaphy. PMID- 8495332 TI - Monitoring and cerebral protection during carotid endarterectomy. PMID- 8495333 TI - Presentation of abdominal tuberculosis to general surgeons. PMID- 8495334 TI - Olfactory bulb removal lengthens the period of circannual rhythms and disrupts hibernation in golden-mantled ground squirrels. AB - Removal of the olfactory bulbs lengthened the period of circannual rhythms (CARs) of body mass and plasma testosterone (T) concentrations in male golden-mantled ground squirrels, but did not otherwise alter their expression. The period of the CAR was approximately 2 months longer in bulbectomized than in sham-operated animals. Peak values of body mass and T were unaffected by bulbectomy. All neurologically intact, but only 50% of bulbectomized, squirrels displayed normal hibernation patterns. We conclude that the olfactory bulbs are not the site of essential circannual oscillators. Circannual reproductive and hibernation cycles of ground squirrels are less subject to modulation by the olfactory bulbs than are the corresponding rhythms of several non-circannual hamster species. PMID- 8495335 TI - Reduced incidence of cortical spreading depression in the course of pentylenetetrazol kindling in rats. AB - Subconvulsive dosages (40 mg/kg) of intraperitoneally applied pentylenetetrazol (PTZ) elicit, after a latency of 1 min, slow potential waves of spreading depression (SD) in the thalamus and 20 s later also in the cerebral cortex of rats. The PTZ-induced SD waves appear only exceptionally in the caudate nucleus and hippocampus. Repeated daily application of 40 mg/kg PTZ elicits kindling of epileptic phenomena manifested by increasing incidence of high-amplitude spikes in the EEG, myoclonic jerks and minimal and later maximal generalized seizures but by decreasing incidence of cortical SD. It is concluded that kindled epileptic activity interferes with the generation of SD waves the reduced incidence of which may contribute to the development of more severe forms of epilepsy. PMID- 8495336 TI - Depression of excitatory synaptic input in rat striatal neurons. AB - Intracellular recording of rat striatal neurons was performed in vitro to investigate posttetanic changes in the excitatory post-synaptic potential (EPSP) elicited by stimulation of the corpus callosum. Tetanic stimulation induced posttetanic potentiation (PTP) in 11 of 12 cells. The PTP decayed in 1-5 min and was followed by either a short or long duration depression of the EPSP in 10 of 12 neurons. The remaining two neurons examined showed a slight enhancement of the EPSP that lasted for 30 min after the tetanus. The group of cells demonstrating short-duration depression (n = 3) were characterized by a decay of the depression to the control level by 15-20 min post-tetanus. The EPSP in the remaining cells showing depression (n = 7) showed a maintained depression for the entire recording session. Blockade of GABAA receptors with bicuculline (30 microM) or NMDA receptors with APV (50 microM) did not effect the induction of long-lasting depression of the striatal EPSP. The data indicates that the corticostriatal pathway can undergo enduring forms of use-dependent synaptic plasticity. This type of synaptic modification may participate in the refinement of movement and contribute to striatal related learning and memory. PMID- 8495337 TI - Responses of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to hemorrhage. AB - The activity of subfornical organ (SFO) neurons that were antidromically identified by electrical stimulation of the rat hypothalamic paraventricular nucleus (PVN) was tested for a response to microiontophoretic application of angiotensin II (ANG II) or hemorrhage (10 ml/kg b.w.t.). Microiontophoretically (MIPh) applied ANG II caused an increased excitability in 24 out of 28 neurons tested and the excitation was blocked by MIPh-applied saralasin (Sar), a specific ANG II antagonist. Of these neurons that responded to ANG II, 14 displayed an increase in neuronal firing in response to hemorrhage, while 10 were unresponsive. The excitatory response to hemorrhage in 5 out of 14 neurons tested was prevented by MIPh-applied Sar, whereas the response of the remaining neurons was not affected. These results show that part of SFO neurons projecting to the PVN may receive neural inputs from the peripheral baroreceptors, and suggest that the inputs may be partially attributable to the involvement of central angiotensinergic circuits. PMID- 8495338 TI - Serotonin depresses excitatory amino acid-induced excitation of cerebellar Purkinje cells in the adult rat in vivo. AB - The modulatory effects of serotonin (5-HT) on excitatory amino acid (EAA)-induced excitations of Purkinje cells (PCs) were examined in urethane-anesthetized adult male rats using microiontophoresis and extracellular recordings. Application of 5 HT had minimal effects on the spontaneous firing rates of PCs but depressed excitations elicited by glutamate (Glu), aspartate (Asp), kainate (KA), and quisqualate (QA), and to a lesser extent those of alpha-amino-3-hydroxy-5-methyl 4-isoxazolepropionate (AMPA). Excitations induced by the metabotropic EAA agonist, (+-)-1-aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD), were unaffected by 5-HT. In summary, 5-HT depressed EAA-mediated excitations with the following rank order of effectiveness: Glu = Asp = KA = QA > AMPA >> t-ACPD. These findings suggest that 5-HT shows some selectivity in its modulation of EAA mediated excitations of PCs and thus may serve an important neuromodulatory role in the cerebellum. PMID- 8495339 TI - Hippocampal plasticity during jaw movement conditioning in the rabbit. AB - Hippocampal CA1 unit responses were recorded during classical conditioning of rhythmic jaw movements in New Zealand White rabbits. Training was accomplished using a 1 kHz tone as the conditioned stimulus (CS) and 1 ml of sweetened water as the unconditioned stimulus (US). The interstimulus interval was 250 ms. Daily sessions consisted of 48 paired trials and six tone alone test trials, with an intertrial interval averaging 60 s. Controls were given explicitly unpaired stimuli. Unit and behavioral conditioned responses developed very rapidly in the trained group, but did not occur in controls. Averaged unit poststimulus histograms showed a correspondence between rhythmic cell discharges and the periodicity of the behavioral conditioned response after training. The results are discussed in relation to a hippocampal role in the modulation of learned movement patterns. PMID- 8495340 TI - Serotonin receptor gene expression in the rat suprachiasmatic nuclei. AB - Serotonin (5HT) is thought to reset the biological clock in the suprachiasmatic nuclei (SCN) in vitro through a postsynaptic 5HT-1a receptor. Thus we examined 5HT receptor gene expression in the SCN by in situ hybridization. On film autoradiograms, 5HT-1c receptor mRNA showed intense SCN hybridization, while 5HT 1b receptor mRNA displayed a weaker signal. Emulsion autoradiograms additionally revealed expression of 5HT-1a and 5HT-2 receptor mRNAs by a few scattered SCN cells. 5HT-3 receptor mRNA was not detected in the SCN, although the transcript was detected elsewhere in the brain. 5HT-1d and -1e receptor mRNAs were not detected in the SCN or elsewhere in brain within the sections examined. The results do not support a major role for postsynaptic 5HT-1a receptors in resetting SCN rhythms. PMID- 8495341 TI - Behavioral and histological changes after repeated brief cerebral ischemia by carotid artery occlusion in gerbils. AB - The effects of repeated brief episodes of cerebral ischemia on passive avoidance learning and hippocampal neuronal degeneration were investigated in gerbils. Latency of step-through was shortened for the entire 7-day period when gerbils were trained at day 3 after 3 episodes of carotid artery occlusion for 2 min each at 60-min intervals. In addition, latency of passive avoidance was shortened for 63 days when gerbils were retrained at 14 days after occlusion. Severe neuronal degeneration in the CA1 regions of the hippocampus was observed 4 and 17 days after occlusion. A close correlation was seen between latency in the passive avoidance response and neurological degeneration of the hippocampal CA1 region. This fact was strongly supported by the results of another experiment that 1 2 min occlusion with almost no neuronal degeneration did not affect learning behavior while 3 1-min occlusions showed neuronal death and impairment of learning behavior of a moderate degree 4 days after occlusion. These results suggest that this gerbil model with carotid artery occlusion is useful for the quantitative measurement of functional changes in the chronic phase of repeated cerebral ischemia. PMID- 8495342 TI - Synaptic N-methyl-D-aspartate receptors in the neonatal rat visual cortex are less sensitive to MK-801 than in adult. AB - The excitatory postsynaptic potential mediated by N-methyl-D-aspartate (NMDA) receptors (NMDA-EPSP) was intracellularly obtained in slices from the visual cortex of adult and 2-week-old rats. Bath application of 0.3 microM (+)-MK-801, an NMDA receptor open-channel blocker, completely blocked NMDA-EPSPs in slices from adult rats. By contrast, in slices from the younger rats, a 10 microM solution was needed for the complete blockade. This difference in sensitivity to an open-channel blocker implies a major developmental change in the conformation of NMDA receptors in situ. PMID- 8495343 TI - Distribution of interleukin 1 beta immunoreactivity within the porcine hypothalamus. AB - The presence and localization of interleukin 1 beta immunoreactivity (IL 1 beta i.r.) was studied in the hypothalamus of four healthy, male pigs at 7 months of age, using immunocytochemical techniques on 100 mu vibratome and 10 mu paraffin sections. IL 1 beta i.r. was found in neuronal cell bodies and their processes within nuclei and fiber tracts of the hypothalamus as well as in varicose fibers, terminals and deposits within the median eminence. In addition, IL 1 beta i.r. was found in the walls of several, but not all, blood vessels and in very few glial cells. PMID- 8495344 TI - Effects of acute and chronic cocaine on the activity of tuberoinfundibular dopamine neurons in the rat. AB - We investigated the effects of acute and chronic cocaine on dopamine (DA) synthesis in tuberoinfundibular dopamine (TIDA) neurons by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the median eminence (ME). Cocaine-induced prolactin (PRL) responses were evaluated for comparison. Acute cocaine inhibited DA synthesis in the ME and decreased circulating PRL. Chronic cocaine did not alter basal DOPA levels in TIDA nerve terminals or PRL levels in plasma. After repeated cocaine injections, cocaine's inhibitory effect on DA synthesis was abolished in the ME while the PRL response to drug was unchanged. These results suggest that TIDA neurons become tolerant to cocaine-induced suppression of DA synthesis after chronic cocaine exposure, but the altered sensitivity of TIDA neurons is not revealed by plasma PRL measures. PMID- 8495345 TI - Adenosine modulation of amino acid release in rat hippocampus during ischemia and veratridine depolarization. AB - This study was undertaken to determine whether endogenous adenosine modulates 'in vivo' neurotransmitter amino acid release via its presynaptic receptors. Two conditions were compared: neuronal depolarization by local infusion of veratridine (600 microM), and transient global ischemia by four-vessel occlusion. Both stimuli were applied for 20 min. Extracellular amino acid (glutamate, taurine/GABA, glycine) variations in concentration were determined in the rat hippocampus by microdialysis and HPLC. Modulation of adenosine receptor activity was objectified by continuous local infusion of an adenosine agonist (R phenylisopropyladenosine R-PIA) or an antagonist (theophylline), starting one hour before stimulation of amino acid release. R-PIA (100 microM) significantly decreased the glutamate release (50%) evoked by veratridine, whereas it did not significantly modify the ischemia-induced glutamate release. In contrast, theophylline did not significantly affect veratridine-induced glutamate release, but it significantly potentiated glutamate efflux (400%) under ischemic conditions. Neither treatment altered the release of the other amino acids. These data suggest that endogenous adenosine appearing in the extracellular space during veratridine-induced depolarization cannot control glutamate release. In contrast, ischemia-induced glutamate release was strongly inhibited by the concomitant increase in extracellular adenosine. PMID- 8495346 TI - Brain ischemia markedly elevates levels of the neurotoxic amino acid, cysteine. AB - The mechanisms underlying cell damage in stroke or during experimental brain ischemia are not fully understood. L-Cysteine, an excitotoxic amino acid that could contribute to tissue damage, is normally found in relatively low levels in brain (ca. 0.05 mumol/g), compared to the cysteine-containing tripeptide, glutathione (GSH, ca. 1.5 mumol/g). We have observed that during brain ischemia in gerbils, levels of cysteine rise 10-13-fold over an 8 h period to 0.66 and 0.62 mumol/g, respectively, in the ischemic hippocampus and striatum. At the same time, levels of GSH fall by 0.84 and 0.94 mumol/g, respectively. The elevated free cysteine may be derived largely from GSH. The levels of cysteine found in ischemic brain are similar to those reported after parenteral administration of neurotoxic doses of L-cysteine to perinatal rats. The remarkable increase in cysteine during brain ischemia, coupled to its neurotoxic properties, may play a role in aspects of brain damage during or following brain ischemia. PMID- 8495347 TI - The role of estradiol and progesterone in phased synaptic remodelling of the rat arcuate nucleus. AB - During the estrous cycle there is a phasic synaptic remodelling in the hypothalamic arcuate nucleus, consisting in a loss and regain of axo-somatic synapses during the 48 h period between the morning of proestrus and the morning of metestrus. Synaptic changes are accompanied by cyclic modifications in the number of intramembrane particles in the plasma membrane of arcuate neuronal somas. To test the effect of the ovarian steroids on arcuate axo-somatic synapses we treated castrated females either with oil vehicle, 17 beta-estradiol, progesterone, or a combination of estradiol and progesterone, and observed them for 48 h. The number of axo-somatic synaptic profiles showed a 33% fall by 24 h after estradiol treatment and returned to control levels by 48 h. The effect of estradiol on axo-somatic synapses was accompanied by a marked and reversible modification of the number of intramembrane particles in the plasma membrane of arcuate neuronal somas. Progesterone alone did not affect the number of axo somatic synaptic profiles nor the number of intramembrane particles, but when administered together with estradiol, blocked the effects of estradiol on neuronal membrane and synapses. PMID- 8495348 TI - Cocaine: a microstructural analysis of its effects on feeding and associated behaviour in the rat. AB - Cocaine (5.6-30 mg/kg, i.p.) was administered to nondeprived male rats trained to eat a palatable sweetened mash. Over a 60-min period, their behaviour was observed and recorded for a microstructural analysis. Cocaine suppressed feeding in a dose-dependent manner (significantly at 10 mg/kg and greater), and this was due in the main to a reduction in the frequency of eating bouts. In contrast, the mean duration of eating bouts was unaffected, except at the highest dose, 30 mg/kg. In addition, the rate of eating was not significantly affected by cocaine at any dose. Time-course data revealed that cocaine, at anorectic doses (10-30 mg/kg), initially suppressed feeding completely, and the duration of this suppression was proportional to the dose. In effect, cocaine delayed the initiation of feeding, thus bringing about the reduction in the number of eating bouts. Cocaine caused some stimulation of locomotor activity and rearing to the side of the observation tank, but did not affect rearing away from the centre, or immobility. Grooming proved to be very sensitive to cocaine's suppressant effect, with substantial inhibition occurring at 5.6 mg/kg (a sub-anorectic dose). These data are compared with previously published work with D-amphetamine and are contrasted with results for selective D1 and D2 dopamine receptor agonists. PMID- 8495349 TI - Epileptic seizure of El mouse initiates at the parietal cortex: depth EEG observation in freely moving condition using buffer amplifier. AB - The initiation site of seizure discharges and the relationship between behavioral manifestations and electroencephalography were investigated in the El mouse, a hereditary epilepsy model. The chronic depth electrodes were implanted stereotaxically into the frontal cortex, parietal cortex, temporal cortex, hippocampus, striatum, amygdaloid complex, non-specific nuclei of thalamus and substantia nigra. Electrical activities were recorded in freely moving condition with use of the buffer amplifier devised in the laboratory and behaviors were monitored simultaneously. Seizure spike discharges started in the parietal cortex and spread out into other brain areas. When the hippocampus was involved, the tonic convulsion occurred behaviorally. The paper describes the first direct evidence of the initiation and propagation of seizure discharges in the brain of El mouse. PMID- 8495350 TI - Cerebellar cortical lesions and reacquisition in classical conditioning of the nictitating membrane response in rabbits. AB - Portions of cerebellar cortex, particularly Larsell's hemisphere VI, have been identified as involved but not essential for the acquisition and retention of classical conditioning of the nictitating membrane (NM) response in rabbit. The present experiment was undertaken to examine the effect of lesions of cerebellar cortical regions projecting to anterior dorsolateral interpositus nucleus. Lesions of relatively equal size, including hemisphere VI and additionally more medial, anterior, or lateral cerebellar cortex were made after rabbits were classically conditioned. The effect of these cerebellar cortical lesions on retention to tone versus light conditioned stimulus (CS) and the timing of the conditioned response was evaluated. In spite of relatively large cerebellar cortical lesions, reacquisition of the conditioned NM response occurred quite rapidly. Whether the lesion was more medial and anterior or more lateral did not affect retention. Retention was significantly poorer with light CS than with tone CS. Timing of CRs was not affected by these lesions of cerebellar cortex, but the lesions spared most of the anterior lobe. The parasagittal zone C3 covering the longitudinal band of tissue from anterior lobe to the paramedian lobule and projecting to dorsolateral anterior interpositus requires additional exploration for its role in classical NM conditioning. PMID- 8495351 TI - Estrogen improves biochemical and neurologic outcome following traumatic brain injury in male rats, but not in females. AB - Phosphorus magnetic resonance spectroscopy was used in conjunction with neurologic motor function tests to assess the effects of estrogen on biochemical and neurologic outcome following traumatic brain injury in male and female rats. Male (n = 18) and female (n = 18) rats were randomly assigned into three groups, and 4 h prior to injury received either 17 beta-estradiol (144 micrograms/kg intraperitoneally), equal volume vehicle (30% ethanol in saline), or no treatment. Traumatic brain injury was induced at 2.8 atm using a fluid percussion injury device, and animals monitored for 4 h using phosphorus magnetic resonance spectroscopy to determine brain intracellular pH, free magnesium concentration and cytosolic phosphorylation potential. Males treated with estrogen demonstrated a significant improvement in free magnesium concentration, and slightly improved values of cytosolic phosphorylation potential after trauma when compared to controls. There was also a significant improvement in post-traumatic motor function at 1 week after trauma. In contrast, estrogen treatment in females lowered cytosolic phosphorylation potential after trauma, but did not affect free magnesium concentration after trauma. Mortality in all female groups was significantly worse than in males. We conclude that estrogen is protective in males, but exacerbates brain injury in females through effects mediated by estrogen receptor binding. PMID- 8495352 TI - The relative effects of selective M1 muscarinic antagonists on rapid eye movement sleep. AB - Three muscarinic antagonists, scopolamine, trihexyphenidyl and biperiden were systemically administered (0, 0.5, 1, 2 and 4 mg/kg) in rats. Scopolamine increased wakefulness and deceased sleep, both slow wave and REM. Trihexyphenidyl increased wakefulness and decreased REM sleep while biperiden decreased REM sleep selectively. The rank order REM-suppressing effect was roughly scopolamine and trihexyphenidyl having a greater suppressing effect than biperiden. These results suggest that the regulation of the sleep-wake cycle is at least partially controlled by the M1 muscarinic receptor. PMID- 8495353 TI - Small sets of putative interneurons are octopamine-immunoreactive in the central nervous system of the pond snail, Lymnaea stagnalis. AB - An antibody raised against conjugated octopamine was applied to map octopamine containing neurons in the central nervous system of the pond snail Lymnaea stagnalis. A small number of octopamine-like immunoreactive neurones occurs in all ganglia, but the pleural ones. The neurons are located either in small clusters or occur individually. Major concentrations of octopamine-immunoreactive neurons can first of all be found in the buccal, cerebral and pedal ganglia. Varicose arborizations were observed in the neuropiles, but peripheral projections of labelled elements could not be traced. We suggest that a set of octopaminergic interneurons would exist in the Lymnaea brain. Mapping of octopamine-immunoreactive neurons given may also facilitate physiological investigations on octopaminergic neurotransmission in the gastropod nervous system. PMID- 8495354 TI - Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats. AB - A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-3,4 dihydroxyphenylalanine (L-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a > 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs. 52 fmol/min; 0.3 mumol/l neostigmine in perfusate). BROMO (4 mg/kg) inhibited the output of striatal ACh in both groups. Whereas the lowest dose of L-DOPA (50 mg/kg) potently stimulated ACh output in lesioned rats, unlesioned rats were significantly less responsive. A higher dose of L-DOPA (100 mg/kg) stimulated ACh output to the same extent in both groups. At the highest dose tested, L-DOPA (200 mg/kg) given to intact rats did not further increase striatal ACh output. Thus, BROMO decreases whereas L-DOPA increases striatal ACh release after systemic application. Therapeutic as well as side effects of L-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought. PMID- 8495355 TI - Bilateral projections of single retinal ganglion cells to the lateral geniculate nuclei and superior colliculi in the albino rat. AB - Employing fluorescent retrograde double/triple labeling, we investigated bilateral projections of single retinal ganglion cells to the lateral geniculate nuclei (LGN) and superior colliculi (SC) in the albino rat. After separate injections of Fast Blue (FB) and Diamidino Yellow (DY), respectively, into the right and left LGN, a large number of retrogradely-labeled cells were distributed all over the retina contralateral to each injection. Ipsilaterally projecting ganglion cells, which were labeled with one tracer injected into the LGN, were found predominantly in the lower-temporal retinal region; approximately 56% (120 140 cells per retina) of them were further labeled with the other tracer injected into the contralateral LGN. The vast majority of these double-labeled cells were of large type (more than 20 microns in diameter). Similar findings were obtained after separate injections of FB and DY, respectively, into the right and left SC, or respectively, into the right SC and left LGN. After separate injections of FB, DY and rhodamine-B-isothiocyanate, respectively, into the bilateral LGN and unilateral SC, or respectively, into the unilateral LGN and bilateral SC, a number of cells triple-labeled with all tracers were localized in the lower temporal retinal region; most of them were of large type. Thus, the bilateral projections from the lower-temporal retinal region representing binocular vision in the rat are indicated to be achieved not only by separate populations of ganglion cells each exclusively serving one side of the brain, but also by axon collaterals from single ganglion cells; the ganglion cells projecting bilaterally to the LGN or/and SC are primarily of large type corresponding probably to the Y cell in the cat retina. PMID- 8495356 TI - Emotional but not physical stress enhances intravenous cocaine self administration in drug-naive rats. AB - Involvement of stress in the etiology of drug dependence has received little attention. In the present study a number of behavioural manipulations were applied and examined for an effect on intravenous cocaine self-administration in drug-naive rats with no prior training in leverpress responding. Self administration rate was measured during five consecutive daily sessions. Stress reduction by handling rats daily for two weeks prior to testing for self administration did not affect cocaine self-administration. Acute physical stress was induced either by a hot plate or by repeated footshocks, and emotional stress was induced by forcing rats to witness another rat being subjected to repeated footshocks. These stressors were applied immediately prior to each cocaine self administration session. Emotional but not physical stress enhanced the rate of cocaine self-administration. It is concluded that emotional distress may increase the rewarding effects of cocaine and may render an individual more susceptible to development of drug dependence. PMID- 8495357 TI - Effect of intravenous administration of apolipoprotein A-IV on patterns of feeding, drinking and ambulatory activity of rats. AB - To characterize the anorectic effect of apolipoprotein A-IV (apo A-IV), we examined the effect of apo A-IV on the patterns of feeding, drinking and ambulation of rats fed ad libitum. A single dose of 200, 135 or 60 micrograms was infused intravenously through a chronically indwelling right atrial catheter just before the dark period. Apo A-IV suppressed food intake by decreasing meal size, but did not affect the interval between meals, the speed of eating, or the latency to eat the first meal after infusion. The anorectic effect of apo A-IV was dose-dependent and was effective for about 3 h after the infusion. The anorectic effect of apo A-IV is specific because inactivation of apo A-IV abolishes its anorectic effect. The anorectic effect of apo A-IV is not shared by apo A-I. Apo A-IV had no effect on drinking behavior or ambulatory activity. The results seem to indicate that apo A-IV specifically decreases the meal size, which supports our hypothesis that apo A-IV may act as a physiological signal for satiation after the ingestion of a lipid meal. PMID- 8495358 TI - Effects of acrylamide on subcellular distribution of elements in rat sciatic nerve myelinated axons and Schwann cells. AB - Electron probe X-ray microanalysis was used to determine whether experimental acrylamide (ACR) neuropathy involves deregulation of subcellular elements (Na, P, S, Cl, K, Ca and Mg) and water in Schwann cells and small, medium and large diameter myelinated axons of rat sciatic nerve. Results show that in proximal but not distal sciatic nerve, ACR treatment (2.8 mM in drinking water) was associated with an early (15 days of exposure), moderate increase in mean axoplasmic K concentrations (mmol/kg) of medium and small diameter fibers. However, all axons in proximal and distal nerve regions displayed small increases in dry and wet weight contents of axoplasmic Na and P. As ACR treatment progressed (up to 60 days of exposure), Na and P changes persisted whereas proximal axonal K levels returned to control values or below. Alterations in mitochondrial elemental content paralleled those occurring in axoplasm. Schwann cells in distal sciatic nerve exhibited a progressive loss of K, Mg and P and an increase in Na, Cl and Ca. Proximal glia displayed less extensive elemental modifications. Elemental changes observed in axons are not typical of those associated with cell injury and might reflect compensatory or secondary responses. In contrast, distal Schwann cell alterations are consistent with injury, but whether these changes represent primary or secondary mechanisms remains to be determined. PMID- 8495359 TI - Specificity of behavioral and neurochemical dysfunction in the chakragati mouse: a novel genetic model of a movement disorder. AB - The chakragati (ckr) mouse is a transgenic insertional mutant that displays lateralized circling behavior, locomotor hyperactivity, hyperexcitability as well as body weight deficits. The mutation is autosomal and recessive. We have previously found that ckr mice have bilateral asymmetric elevations in striatal dopamine (DA) D2-like (D2, D3 and/or D4), but not D1-like (D1 and/or D5) receptors. Predictably, these mice increase turning in response to the D2-like agonist quinpirole and spontaneously rotate contralateral to the striatal side with the higher D2-like receptors. The overall objective of the present study was to assess the neurochemical specificity of the mutation in ckr mouse, particularly since motor behaviors can be elicited by a multitude of brain regions and neurotransmitter systems within the basal ganglia. Using quantitative receptor autoradiography, we examined the regional distribution of DA uptake sites and 5-HT1A, 5-HT1B/1D, GABAA and mu opioid receptors. Also, we wanted to determine whether increased behavioral laterality as seen in rotation is evident with another test of laterality, such as lateral paw preference. The ckr mice showed greater paw preferences than normal mice; however, neither the degree nor direction of these preferences correlated with rotational behavior. The ckr mice showed moderate decreases in the density of DA uptake sites in all subregions of the striatum, but not in the nucleus accumbens or olfactory tubercle. Interestingly, these decreases in ckr mice were not accompanied by a reduction in striatal tissue DA content. 5-HT1 and mu opiate receptor populations were normal in ckr mice. However, GABAA sites in the mediodorsal thalamus and superior colliculus were bilaterally and asymmetrically elevated in ckr mice. These data are consistent with the idea that the motor phenotypes of the ckr mouse result from specific disturbances within nigro-striatal, striato-pallido-thalamic and striato-nigro-collicular circuitry. The implications of these and past findings are discussed in relation to current thinking about hyperkinetic motor syndromes in humans involving reduced basal ganglia outflow. PMID- 8495360 TI - Cocaine inhibits hippocampal long-term potentiation. AB - Long-term potentiation (LTP) is a form of synaptic plasticity that may underlie learning and memory. The experiments reported here demonstrate that cocaine blocks the induction of LTP at the excitatory synapses in the CA1 region of the hippocampus, but does not appear to do so by blocking NMDA receptors or channels. Once LTP had been established, however, cocaine had no effect on the potentiated response. Cocaine was also able to block LTP initiated by superfusing slices with 25 mM TEA. The ability to block LTP was shared by the local anesthetics lidocaine and procaine, but not by tetrodotoxin, suggesting that the blockade of sodium channels alone did not disrupt LTP. Biochemical experiments demonstrated that cocaine can inhibit phosphorylation of purified Synapsin I by Ca2+/calmodulin dependent protein kinase II. This effect, presumably mediated by effects on calmodulin, is a previously unreported action of cocaine, and suggests that cocaine at high dose levels might disrupt types of learning that are mediated by an LTP-like mechanism. PMID- 8495361 TI - Age-related deterioration in conditional avoidance task in the SAM-P/10 mouse, an animal model of spontaneous brain atrophy. AB - A novel inbred strain of mouse 'SAM-P/10' (Senescence Accelerated Mouse) is a model of age-related brain atrophy characterized by age-related loss and shrinkage of neurons in the cerebral neocortex. Age-related changes in learning and memory skills of SAM-P/10 mice were investigated using a newly developed conditional avoidance task in a T-maze. Comparisons were made with findings in the SAM-R/1 strain which shows a little loss and no shrinkage of neocortical neurons. Four-month-old SAM-R/1 and SAM-P/10 performed well during a 10-day training schedule of the conditional avoidance task. SAM-R/1 mice over 17 months of age were slower learners than younger SAM-R/1 mice but reached nearly the same high percentage avoidance as seen in the 4-month-old mice during the last 4 days of the schedule. Performance of the SAM-P/10 mice gradually worsened with aging and 10- to 12-month-old SAM-P/10 mice could not reach the percentage avoidance seen with the 4-month-old mice, even after the 10-day training. When the mean percentage of successful avoidance or escape behavior on every training day was plotted, the curves were much the same for both SAM-R/1 and SAM-P/10 mice, of any age. These results show that aged SAM-P/10 mice retained the left-right turning discrimination in the T-maze and lost the ability to predict the forthcoming aversive shock by associating conditioned stimulus and unconditioned stimulus. PMID- 8495362 TI - Stimulation of tumor necrosis factor-alpha production by mycoplasmas and inhibition by dexamethasone in cultured astrocytes. AB - Elevated levels of tumor necrosis factor-alpha (TNF alpha) and other cytokines and eicosanoids in the central nervous system (CNS) have been noted in several human neurologic diseases, including multiple sclerosis and AIDS dementia. Recently it was shown that glial cells, especially astrocytes, are a major source of cytokines and eicosanoids. In the present study we have shown that astrocytes derived from fetal rat brain triggered by mycoplasmas produce TNF alpha and prostaglandin E2 (PGE2). Addition of mycoplasma (Mycoplasma capricolum isolated from sheep and M. fermentans KL-4 from human) at a concentration of 1-50 micrograms protein/ml (2 x 10(7)-10(9) colony forming units/ml), as well as lipopolysaccharide (5 micrograms/ml), led to a 200-500-fold increase in TNF alpha and a 2.5-4.5-fold increase in PGE2 production. Preincubation of the cells with the synthetic glucocorticoid, dexamethasone (2 x 10(-5)-2 x 10(-8) M), as well as with the natural hormone, corticosterone, markedly inhibited the secretion of both TNF alpha and PGE2. Thus, mycoplasmas can be added to the wide variety of agents that stimulate glial cells to produce cytokines and eicosanoids, and may contribute to various CNS pathological manifestations. In addition, the ability of glucocorticoids to inhibit particularly the stimulated productions of TNF alpha and PGE2 may explain at least in part the therapeutic benefit of these agents in CNS inflammation and demyelination. PMID- 8495363 TI - Metabolic changes associated with altering blood glucose levels in short duration forebrain ischemia. AB - 31P nuclear magnetic resonance spectroscopy was used to follow changes in cerebral pH and high-energy phosphate metabolites during forebrain ischemia in hypo-, normo- and hyperglycemic rats, and during reperfusion in animals in which the blood glucose level was altered post-ischemia. Pre-ischemia, no differences in the levels of inorganic phosphate (Pi) and adenosine triphosphate (ATP) relative to phosphocreatine (PCr) or in tissue pH between blood glucose groups were observed. During ischemia, the decrease in tissue pH was found to be dependent on the pre-ischemic blood glucose concentration, being greatest in hyperglycemic and least in hypoglycemic animals. The increase of Pi, a consequence of the hydrolysis of high-energy phosphate metabolites, also depended on the blood glucose concentration, being greatest in hypoglycemic and least in hyperglycemic animals. ATP and PCr decreased more rapidly in hypoglycemic rats compared to normo- or hyperglycemic animals, which showed no differences in the rates of depletion. Post-ischemic hyperglycemia resulted in delayed recovery of tissue pH in all groups and of PCr and ATP in animals hyperglycemic throughout the experiment. Insulin administration immediately following ischemia increased the rate of recovery of pH, ATP and PCr in hyperglycemic animals. ATP remained significantly below pre-ischemia level in all subgroups at 1 h post-ischemic, while PCr was lower than it was pre-ischemia only in those subgroups hyperglycemic prior to and/or following ischemia. In animals maintained severely hypoglycemic throughout the experiment, erratic blood pressure and cerebral energy failure during the reperfusion interval were observed. PMID- 8495364 TI - GABAergic neurons in human spinal cord cultures: a computer-aided analysis of normal and thienyl-phencyclidine-treated cells. AB - gamma-Aminobutyric acid (GABA)-containing neurons were studied in dissociated cell cultures of human spinal cords from 6-10-week-old fetuses using immunohistochemistry with anti-GABA antibodies. Light microscopy showed two types of immunoreactive (IR) neurons: (1) IR neurons with short neuritic processes remaining near the cell body (small neuritic tree neurons); and (2) IR neurons with long neuritic processes extending far from the cell body (large neuritic tree neurons). Both types were studied at different ages in vitro, in control and in thienyl phencyclidine (TCP)-treated cultures by means of computer reconstructions and morphometric parameters. A discriminant analysis permitted the recognition of three populations: whatever the age, the control and TCP treated neurons with small neuritic trees were not discriminated from each other and were considered to be one population whereas the 98 DIV control and both 21 DIV and 98 DIV TCP-treated cells with large neuritic trees were clearly separated from each other and from the small cell population. In all models, an astrocytic labeling, weaker than that of the neurons, was observed. The nature of these neurons (probably interneurons) intrinsic to the spinal cord is discussed in view of previous findings concerning the anatomical distribution and organization of the GABAergic system in the spinal cord. PMID- 8495365 TI - Activation of brainstem catecholaminergic neurons by conditioned and unconditioned aversive stimuli as revealed by c-Fos immunoreactivity. AB - In an attempt to define areas of the brain that respond to stressors and influence immune function, we have previously identified stress-induced, c-Fos immunoreactive areas of the diencephalon. We found that c-Fos was strongly expressed in cells of the paraventricular nuclei (some of which contain corticotropin-releasing hormone (CRH)) and other hypothalamic areas directly associated with autonomic function. To further characterize the presumptive pathways mediating stress-induced immune alterations, including the assessment of brainstem catecholaminergic neuron involvement, the induction of c-Fos immunoreactivity was examined in the brainstem of rats exposed to conditioned and unconditioned, immunomodulating stimuli. In response to electric footshock (the unconditioned stimulus (US)), c-Fos immunoreactivity was strongly induced in the noradrenergic neurons of the locus ceruleus (A6), the nucleus of the solitary tract (A2/C2), the ventral lateral medulla (A1/C1), A5, and A7, as well as in unidentified neurons of the dorsal and ventral subdivisions of the periaqueductal gray (PAG), and in the serotonergic neurons of the dorsal raphe nuclei. Conditioned animals re-exposed to the conditioned stimulus showed c-Fos induction in these same areas but to a lesser degree. Control animals exposed only to the conditioning stimulus (CS) (electronic tone) in the absence of the US, expressed very little, if any, c-Fos activity in the above loci except for a small degree of baseline expression in the PAG. These results further confirm the role of autonomic and endocrine pathways as mediators of the stress response and will help to more fully characterize the pathways of stress-induced immune alteration. PMID- 8495366 TI - Androgen concentration by a sexually dimorphic population of tachykinin immunoreactive neurons in the rat ventral premammillary nucleus. AB - Strong connections with sexually dimorphic nuclei suggest that the ventral premammillary nucleus (PMv) may be involved in the mediation of reproductive behavior. Steroid autoradiography and immunohistochemistry were used to show that: (1) there is a sex difference in the numbers of PMv neurons that contain tachykinin peptides, (ii) dihydrotestosterone concentrating cells are densely distribution in the PMv and about a quarter of these also contain immunoreactive tachykinin and, (iii) size of the immunoreactive tachykinin population does not respond to alterations in levels of gonadal steroids in adulthood. Thus the PMv appears to make a contribution to the regulation of sexual behavior through androgen-concentrating, tachykinin-containing pathways that are anatomically distinct from estrogen receptive circuitry. PMID- 8495367 TI - Decrease in amyloid precursor protein precedes hippocampal degeneration in rat brain following transient global ischemia. AB - We have studied amyloid precursor protein (APP) expression in rat brain following transient global ischemia. Ischemic damage 24 h after 30 min of four-vessel occlusion (4VO) was limited to the caudate nucleus; hippocampal pyramidal neurons appeared histologically normal by light microscopy. Consistent with ongoing neurodegeneration in the caudate nucleus, microtubule-associated protein-2 (MAP 2) levels assessed by immunoblots were significantly reduced in homogenates of caudate nucleus after 4VO. MAP-2 levels In the hippocampus were comparable to control values. In contrast, full length APP levels in both the caudate nucleus and hippocampal homogenates were significantly decreased following 4VO despite normal hippocampal morphology at 24 h. These findings suggest that decrements in full length APP precede overt neuronal damage and may play a role in the subsequent delayed neurodegeneration in the hippocampus. PMID- 8495368 TI - Intrinsic and synaptic properties of turtle red nucleus neurons in vitro. AB - Burst discharges in the red nucleus are correlated with discrete limb movements. Intracellular recordings from red nucleus neurons in the in vitro turtle brainstem-cerebellum was performed to elucidate mechanisms underlying these bursts. Depolarizing intracellular current injection failed to demonstrate endogenous membrane currents that might produce burst discharges, and neurons did not exhibit significant spike frequency adaptation, which is a characteristic of synaptically driven bursts. Responses of red nucleus neurons to synaptic input demonstrated a late, slow depolarizing synaptic potential (slow EPSP) having a latency of 9-12 ms, and a maximal duration of 600 ms. it is concluded that neither intrinsic membrane responses, nor the duration of the slow EPSP, can fully account for the behavior of red nucleus neurons during burst discharge. We hypothesize that activity in the red nucleus is driven by a gradual recruitment of NMDA receptors, and lpr by polysynaptic excitatory pathways. PMID- 8495369 TI - Levorphanol and swim stress-induced analgesia in selectively bred mice: evidence for genetic commonalities. AB - Two independent selective breeding programs have developed divergent lines of mice expressing either high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland) or high and low levorphanol analgesia (HAR/LAR lines; Portland, OR). In the present study, mice from both programs were tested for both levorphanol analgesia (2 mg/kg) and an opioid-mediated swim stress-induced analgesia (3 min swimming in 32 degrees C water) in the hot-plate test. Mice selected for high and low levorphanol analgesia displayed high and low swim stress-induced analgesia, respectively; mice selected for high and low swim stress-induced analgesia displayed high and low levorphanol analgesia, respectively. This pattern of correlated responses suggests a high degree of common genetic determination in opiate and swim stress-induced analgesia. These findings also suggest that individual differences in analgesic responsiveness to opiate drugs result from genetically determined individual differences in endogenous pain inhibitory mechanisms. PMID- 8495370 TI - Transient cerebral vasodilatory effect of neuropeptide Y mediated by nitric oxide. AB - The effects of intracarotidly injected neuropeptide Y (NPY; 0.1 micrograms/kg) on the local cerebral blood volume (CBV) and blood flow (CBF) in the parieto temporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative crosssectional area of the cerebral microvascular beds. NPY immediately caused transient but significant increases in CBV and CBF, which lasted for less than 5 min. Thereafter, CBV returned to and remained at the control level, although CBF was decreased by 30-40% for 60 min during the monitoring period. The CBV increases after NPY were prevented by a 15 min preinjection of 0.35 mg/kg/min of NG-monomethyl-L-arginine (L-NMMA), which is a competitive blocker of nitric oxide synthesis. The CBV increases after NPY reappeared following a 15-min administration of 0.25 mg/kg/min of L-arginine, which is a precursor of nitric oxide. We conclude that NPY administered in vivo exerts a previously unreported effect of transient vasodilatation on the cerebral microvessels. This action appears to be mediated by nitric oxide, which is a major candidate as an endothelium-derived relaxing factor (EDRF). PMID- 8495371 TI - SLOW and FAST lateral geniculate neurons are differently influenced by acetylcholine. AB - In rats anesthetized with urethane, potentials of 108 neurons were recorded extracellularly in the dorsal part of the lateral geniculate body (dLGB). Neuronal responses to diffuse light stimuli were studied before and during the iontophoretic application of acetylcholine (ACh). Although individual cells of all groups of functionally different neuron types could be influenced by ACh, responses to flashes were most pronounced and uniformly enhanced in the groups of SLOW ON-like cells located in the dorsolateral and caudal parts of the dLGB. The activity in primary response phases to light flashes increased also in caudally located SLOW OFF-like cells. In the group of ventromedially located FAST OFF-like cells the postinhibitory offdischarge in the response to flash was significantly augmented. Only few cells of FAST ON-like groups were affected and some of them inhibited by ACh. off PMID- 8495372 TI - Behavioral studies of emetic sensitivity in the ferret. AB - The ferrets' responsiveness to several known and putative emetic agents was evaluated using a variety of agents that were injected subcutaneously and/or intravenously. Apomorphine was consistently emetic at relatively high doses (100 micrograms/kg) when injected subcutaneously in large male ferrets (> or = 1.4 kg). The responsiveness to apomorphine was anomalous in that subcutaneous injections produced a more consistent response than intravenous ones. In addition, ferrets rapidly become tolerant or tachyphylactic to subcutaneously administered apomorphine. Area postrema ablation, but not abdominal vagotomy, rendered ferrets refractory to the emetic effects of apomorphine. This species, relative to dog and humans, proved to be insensitive to a variety of pharmacologic agents including angiotensin II, gastrin, histamine, Leu enkephalin, neurotensin, serotonin, and vasopressin. Cisplatin elicited forceful retching and emesis. Emetic responses were obtained with substance P and Met enkephalin in individual animals but were inconsistent. Sensitivity to DAGO [D Ala2,MePhe4,Gly-ol5 enkephalin] was variable. Results of this study indicate that the ferret is not an optimal model for all forms of emesis. PMID- 8495373 TI - Noninvasive subthreshold auricular electrical stimulation reduces the severity of precipitated and abrupt opiate withdrawal. AB - The objective of this study was to use noninvasive, subthreshold auricular electrical stimulation (AES) as a treatment to reduce the severity of precipitated and of abrupt opiate withdrawal. Sixty-four male Sprague-Dawley rats were divided into six groups. The first three groups were used to study the effects of AES on naloxone-precipitated withdrawal; the other three groups were used to examine the influence of AES on abrupt withdrawal. Morphine dependence was induced by multiple injections of the drug on an incremental staircase dosage regimen for 6 days. The results obtained from first three groups show that AES reduced the severity of the withdrawal signs precipitated by naloxone injection (0.5 mg/kg SC) by more than 75% (p < 0.01). The observations obtained from the other three groups show that AES reduced the severity of abrupt withdrawal for at least 4 h as assessed by measuring the locomotor behavior of the animals. This study demonstrates that noninvasive subthreshold AES is effective in reducing the severity of precipitated and of abrupt opiate withdrawal. PMID- 8495374 TI - Cardiovascular responses to blockade of GABA synthesis in the hypothalamus of the spontaneously hypertensive rat. AB - Previous studies have suggested that a decreased inhibitory input onto neurons within the posterior hypothalamus (PH), a known pressor area, may contribute to hypertension in the spontaneously hypertensive rat (SHR). Recent experiments from this laboratory have shown that neurons in the PH of the SHR have an altered and elevated discharge frequency compared to those in the normotensive rat. In addition, biochemical studies have reported that there is a decreased concentration of the inhibitory neurotransmitter, GABA, in the hypothalamus of the SHR. The objective of the present study was to assess any variations in GABAergic modulation of cardiovascular activity in SHRs compared to normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Arterial pressure and heart rate responses to microinjections of the GABA synthesis inhibitor 3 mercaptopropionic acid (3-MP) into the posterior hypothalamic area of anesthetized young (6-8 weeks) and mature (11-16 weeks) hypertensive and normotensive rats were recorded. Microinjection of 3-MP elicited increases in arterial pressure of 17.4 +/- 3.9 mmHg, 18.1 +/- 7.8 mmHg, 16.9 +/- 6.4 mmHg, and 10.4 +/- 3.5 mmHg in the mature WKY, mature SD, young WKY, and young SHR, respectively. In addition, heart rate was elevated by 33.2 +/- 21.9 beats/min, 70.0 +/- 25.3 beats/min, 56.3 +/- 15.0 beats/min and, 45.9 +/- 10 beats/min in the mature WKY, adult SD, young WKY, and young SHR groups, respectively. In contrast, microinjection of 3-MP into the posterior hypothalamus of adult SHRs produced no significant change in arterial pressure (-5.0 +/- 1.8 mmHg) or heart rate (+5.3 +/- 6.1 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495375 TI - Genesis of biphasic thermal response to intrapreoptically microinjected clonidine. AB - Intrapreoptic (IPO) microinjections of various agents cause unavoidable brain tissue injury, often resulting in prostaglandin (PG)-mediated core temperature (Tc) rises. However, IPO microinjection of the alpha 2-adrenoreceptor agonist clonidine (Clo) generally evokes a Tc fall, seemingly avoiding the influence of injury due to the microinjection procedure per se. To clarify this, we microinjected bilaterally into the preoptic/anterior hypothalamus of conscious guinea pigs various doses of Clo dissolved in pyrogen-free saline (PFS, 1 microliter/side). Clo caused biphasic hypo-/hyperthermic responses. The initial hypothermia was dose dependent: no decrease in Tc for 0.1 microgram of Clo, -0.4 +/- 0.1 degree C for 0.5 microgram, -0.9 +/- 0.1 degree C for 1.5 microgram, and 1.2 +/- 0.1 degree C for 5.0 micrograms. During the hyperthermic phase, Tc increased to a dose-independent level (1.0-1.5 degrees C), remaining there up to 5 h postinjection. PFS microinjected IPO also induced hyperthermia, but without any initial Tc decrease. This Tc rise was delayed by 100 min when the cyclooxygenase inhibitor indomethacin (Indo, 50 micrograms/microliters) was injected. Nontreated animals (time controls) maintained Tc at baseline levels during the whole experiment. The alpha 2-antagonist rauwolscine (2 micrograms/side), microinjected IPO 10 min before Clo (0.5 microgram/side), abolished the hypothermic without affecting the hyperthermic response phase; Indo (10 mg/kg), injected intramuscularly 20 min after the IPO microinjection of Clo (0.5 microgram), significantly attenuated the hyperthermic phase. These results confirm that an artifactitious, PG-mediated Tc rise consequent to nonspecific brain tissue injury contaminates the thermal response to agents (hyper- or hypothermizing) microinjected IPO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495376 TI - Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions. AB - Chronic rats, prepared with unilateral injections of kainic acid in the left basal forebrain, displayed prominent large amplitude slow wave activity in the neocortex ipsilateral to the injection. Oxotremorine and pilocarpine, given systemically following pretreatment with methyl scopolamine to block peripheral muscarinic effects, restored low voltage fast activity (LVFA) in a dose-related manner. Oxotremorine was more potent than pilocarpine. Arecoline was not consistently effective. Tetrahydroaminoacridine abolished abnormal 4-6 Hz rhythmical slow waves in the left neocortex but had little effect on large amplitude irregular slow waves. Direct-acting cholinergic agonists can restore near-normal neocortical activity after extensive cholinergic deafferentation of the neocortex. PMID- 8495377 TI - Spontaneous activity of cat spinal ganglion neurons in vivo. AB - Recordings were made from L4-S1 spinal ganglion neurons of anesthetized cats while their associated dorsal root and the sciatic nerve were left intact, locally anesthetized, or locally anesthetized and sectioned. In all three experimental conditions spontaneous discharges were recorded. These discharges occurred in the absence of any electrical stimulation of the dorsal root or sciatic nerve, and were not due to peripheral exploration of receptive fields or sustained firing in joint or muscle afferents. The spontaneous discharges were relatively rhythmic, and their firing frequency ranged from 5 to 100 impulses per s. Interactions between spontaneous and electrically evoked discharges were observed that depended on the impulse's frequency of firing. High frequency discharges always abolished low frequency impulses regardless of whether these latter were spontaneous or evoked. Extra spikes and postspike events that followed impulses evoked by stimulation of the dorsal root or sciatic nerve were also recorded from some spinal ganglion neurons. These results suggest that spontaneous discharges may originate within the spinal ganglion itself, and that they can occur under normal circumstances. PMID- 8495378 TI - Characteristics of action potentials recorded from cat spinal ganglion neurons in vivo. AB - Action potentials were recorded intracellularly from L4-S1 dorsal root ganglion (DRG) neurons of anesthetized cats. Based on the shape of their waveforms the action potentials were classified as either typical (n = 49) or atypical (n = 8). The atypical potentials were characterized by a slowly rising, well-defined early depolarization of small amplitude and long duration. This kind of prepotential randomly triggered spike potentials with varying latencies. The average rise time, duration, and area of atypical potentials were significantly different than those of typical ones. In some DRG neurons, the afterhyperpolarization was preceded by a delayed repolarization, or was followed by postspikes and long lasting afteroscillations. In others, small depolarizations could be recorded during subthreshold stimulation. These depolarizations arose slightly later than the spike potential, and were all or none, with relatively stable onset latency and size. These results are explained by postulating the presence of chemical synapses and/or electrotonic coupling in the DRG. PMID- 8495379 TI - Ascending afferent regulation of rat midbrain dopamine neurons. AB - Standard, extracellular single-unit recording techniques were used to examine the electrophysiological and pharmacological responsiveness of midbrain dopamine (DA) neurons to selected, ascending afferent inputs. Sciatic nerve stimulation-induced inhibition of nigrostriatal DA (NSDA) neurons was blocked by both PCPA (5-HT synthesis inhibitor) and 5,7-DHT (5-HT neurotoxin), suggesting mediation by a serotonergic (5-HT) system. Direct stimulation of the dorsal raphe (which utilizes 5-HT as a neurotransmitter and inhibits slowly firing NSDA neurons) inhibited all mesoaccumbens DA (MADA) neurons tested. Paradoxically, DPAT, a 5 HT1A agonist which inhibits 5-HT cell firing, enhanced sciatic nerve stimulation induced inhibition of NSDA neurons. MADA neurons were not inhibited by sciatic nerve stimulation and, therefore, could not be tested in this paradigm. In contrast to the dorsal raphe, electrical stimulation of the pedunculopontine tegmental nucleus preferentially excited slowly firing NSDA and MADA neurons. Thus, both excitatory and inhibitory ascending afferents influence the activity of midbrain DA neurons, and intact 5-HT systems are necessary for sciatic nerve stimulation to alter DA cell activity. However, the role that 5-HT plays in mediating peripheral sensory input remains unclear. PMID- 8495380 TI - Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study. AB - Development and resolution of the lesion produced by occlusion of the middle cerebral artery (MCAO) was studied through quantitative planimetry and histologic/immunohistochemical techniques. MCAO, performed in spontaneously hypertensive rats (SHR), initially (1-3 days) produced large, consistent cerebral cortical infarctions and an increase in ipsilateral hemispheric size (i.e., swelling) quantitated by planimetry on 2,3,5-triphenyltetrazolium chloride (TTC) stained gross tissue sections. These initial changes correlated well with changes identified from 2 h to 3 days using hematoxylin and eosin stained histologic tissue sections and immunohistochemical techniques including: the progressive development of a cortical area of pan necrosis, infiltration of neutrophils into infarcted tissues, and activation of astroglia. During the initial 2 days following MCAO, glial fibrillary acidic protein immunoreactive cells increased in number and became larger and more intensely fluorescent medial to the cortical infarct. At 5 to 15 days, both the infarct and the ipsilateral hemisphere decreased in size. These changes correlated with the presence of abundant macrophages, and cavitation of the lesion along its medial border. Also during this period, a loose connective tissue matrix formed along the superficial aspect of the infarct. This connective tissue contained fibroblasts, extracellular matrix immunoreactive for laminin and collagen, capillary buds indicating neovascularization, and abundant macrophages. By the final timepoint (30 days), necrotic tissue could no longer be detected in either gross or histologic tissue sections, the inflammatory infiltrate had resolved, and the connective tissue was removed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495381 TI - Acute cocaine alters cerebrovascular autoregulation in the rat neocortex. AB - Although cocaine abuse has been associated with an increased incidence of cerebrovascular accident, the underlying mechanisms are unknown. In this study we have investigated the effects of cocaine upon the autoregulation of local cortical blood flow (lCBF) during hypertension. Hypertension was induced in conscious rats by intravenous infusion of angiotensin-II (5 micrograms/ml; 0.5 2.5 ml/h), and animals were subsequently injected IV with either cocaine-HCl (5 mg/kg) or saline, prior to the measurement of lCBF of glucose utilization (lCGU) using [14C]-iodoantipyrine or [14C]-2-deoxyglucose quantitative autoradiography, respectively. Hypertension alone (< 155 mmHg) did not significantly alter lCBF in any cortical areas examined. However, at higher mean arterial blood pressure (MABP), lCBF increased focally (+265%) in parietal cortex. Cocaine did not alter lCBF in normotensive animals, but with increasing levels of hypertension (MABP > 145 mmHg), all cocaine-treated rats showed focal increases (200-400%) in lCBF in parietal cortex. Glucose use remained relatively unaffected in all treatment groups. This hyperaemia in cocaine-treated rats at MABP below the normal upper limit of autoregulation may provide a mechanism to explain haemorrhagic stroke in cocaine abusers. PMID- 8495382 TI - Implication of testosterone metabolism in the control of the sexually dimorphic nucleus of the quail preoptic area. AB - In quail, testosterone (T) activates male copulation and affects the volume and cytoarchitectonic organization of the medial preoptic nucleus (POM). T metabolism (especially its aromatization) is critical for the production of these behavioral effects. We wondered whether T metabolism is also playing a role in the induction of the morphological changes in POM. We compared the effects of T and of its metabolites in this nucleus. To obtain an independent evaluation of the role played by aromatase, morphological effects of T associated or not with the aromatase inhibitor R76713 were also assessed. As previously observed, T increased the POM volume and the cross-sectional area of the neurons in the lateral part of the nucleus. The effects of T on the neurons in the lateral POM were mimicked in part by the combined treatment with estradiol and 5 alpha dihydrotestosterone. They were also blocked by the aromatase inhibitor. This suggests that T aromatization plays a critical role in the mediation of the cytoarchitectonic effects of T. A specific role for androgens alone remains to be established. PMID- 8495383 TI - Novel diet consumption and body weight gain are reduced in rats chronically infused with lithium chloride: mediation by the chemosensitive area postrema. AB - The effects of chronic lithium chloride infusions on consumption of, and subsequent preferences for, a novel diet were examined in rats with ablations of the area postrema (AP) and sham-lesioned control rats. Osmotic minipumps (Alza), filled with a saturated aqueous solution of LiCl (63 g/100 ml), were implanted in the peritoneal cavity of half of the lesioned rats (n = 9) and half of the control rats (n = 8). The remaining rats received empty pumps (n = 9 and n = 7 for lesioned and controls, respectively). The LiCl or sham drug phase was paired with free access to a highly palatable novel diet (AIN diet) during a 7-day conditioning period. Subsequent preferences for the novel diet relative to a familiar diet (ground Purina lab pellets) were determined using a two-food choice procedure. The only group to show a persistent and significant reduction in novel food consumption during the conditioning phase was the sham-lesioned group infused with LiCl (p < 0.01). This group also exhibited a marked aversion for the novel diet, indicative of a conditioned food aversion (CFA), during the preference tests. No significant differences in novel diet consumption or in novel diet preference were found between the two AP-lesioned groups. This study provides evidence that anorexia and CFAs to a novel diet, induced with chronic infusions of lithium, are abolished by destruction of the chemosensitive area postrema. PMID- 8495384 TI - Inhibition of peripheral fast synaptic inputs to celiac ganglion neurons by splanchnic preganglionic fibers in the cat. AB - Fast nicotinic transmission was studied in vitro in isolated cat celiac ganglion neurons using intracellular recording techniques. Fast synaptic activation was evoked by stimulation (0.1 Hz) of the anterior peripheral rami. A long-lasting inhibition of this response was triggered by repetitive splanchnic stimulation (30-50 Hz) for 10 s. Evidence is given that this inhibition occurs at presynaptic level. Our results indicate that central inputs modulate transmission of fast synaptic peripheral inputs to prevertebral ganglionic neurons. This would be another integrative mechanism in the prevertebral ganglia. PMID- 8495385 TI - [Purification of leucine-endopeptidase from Saccharomyces cerevisiae inner mitochondrial membrane]. AB - Several proteolytic activities have been extracted from isolated yeast mitochondrial inner membranes, in the presence of Tween 20. Absence of matrix and cytoplasmic contamination has been checked. A leucine-endopeptidase has been purified to homogeneity. It has an apparent molecular mass of 66 kDa and a pHi near 8.6. It is a serine-protease, which hydrolyses synthetic polypeptides whose leucine carboxylic group is engaged, as well as various macromolecular proteins; its optimal pH is 7.2. PMID- 8495386 TI - [Effects of adriamycin on axotomized neurons in regeneration chamber model of the peripheral nerve]. AB - Peripheral nerve tubulization is mainly used to study regeneration. We used this model to study the effects of adriamycin on axotomized dorsal root ganglion neurons after local administration of this drug in silicone chambers placed on the proximal stump of a sectioned nerve. No massive neuronal degeneration has been detected in the dorsal root ganglia. However, adriamycin induced a significant atrophy in axotomized neurons. Our observations indicate that this effect is due to blood borne transport of adriamycin, rather than retrograde axonal transport, and that it affects also axotomized neurons that are not directly exposed to adriamycin at the sectioned stump of their axon. PMID- 8495387 TI - Alpha rhythm in the cat thalamus. AB - In cats, electrocortical rhythms at about 10 Hz displaying common characteristics with the human alpha rhythm [1] were recorded from the part of the visual cortex that includes the anterior half of areas 17 (on the cortical convexity), of area 18 and of their common limit, representing the projection of the lower contralateral visual quadrant and that of the lower vertical meridian. It is shown here that activities highly correlated with these rhythms and at the same frequency, were recorded from the anterior half of the laminar dorsal lateral geniculate body (mediodorsal part of layer A), and also from a limited area medial to this nucleus. The cat thalamocortical alpha system thus appears to concern only the projection of the lower quadrants, probably excluding the area centralis itself. PMID- 8495388 TI - Safeguarding the quality of epidemiological caries data at a time of changing disease patterns and evolving dental services. PMID- 8495389 TI - Prevalence of dental enamel defects in 6, 7 and 8-year-old children resident in West Bromwich, Sandwell, UK. AB - Prompted by a parent's concern about the enamel defects of his daughter's teeth, the present study surveyed a sample of 6-8-year-old children using a modified developmental defects of enamel index. The aim was to establish the prevalence of such defects in permanent teeth of children in West Bromwich and to investigate differences according to social class or ethnic origin. Results showed that the mouth and tooth prevalence of enamel defects in Sandwell were not higher than those reported in similar studies. Analysis revealed no statistical significance between the tooth or mouth prevalence of defects according to the social class of the child although significant differences were found between children of Asian and non-Asian origin. A greater prevalence of diffuse defects was found among non Asian children, conversely there was a greater prevalence of demarcated defects among Asian children. Recommendations are made in relation to the conduct of future studies of a similar kind with regard to the number of teeth examined, the presentation of reproducibility results and the evaluation of the cosmetic appearance of the teeth. PMID- 8495390 TI - Changes in sick leave among Swedish dental patients after treatment for dental fear. AB - The most obvious consequence of a genuine dental phobic reaction is the avoidance of necessary dental care. Previous research has indicated that such avoidance results in deterioration of the oral status, which subsequently worsens patients' well-being and quality of life. The authors' previous investigations have shown overt behavioural and social effects by an increased time spent on sick leave compared with the public experience. Self-reports by patients also indicated that the time spent on sick leave was reduced after successful treatment for dental fear. The present investigation assessed the frequency of sick leave days among patients with dental fear and avoidance with regard to successful or unsuccessful treatment for dental fear (subsequent regular dental visit habits). A sub-sample of the fear group was compared with a group of matched controls. Data were collected from the official register of the National Health Insurance Board. It was revealed that the number of sick leave days was significantly reduced after treatment for dental fear among treated patients. This effect was also confirmed by a significant post-treatment difference between treated patients and those who discontinued or never started treatment. When compared with a matched control group, the positive change was further supported by a significant pre-treatment difference and a non-significant post-treatment difference. PMID- 8495391 TI - Measures of dental beliefs and attitudes: their relationships with measures of fear. AB - Emergency dental and fearful dental patients were questioned in order to investigate the relationship between dental fear and different dental beliefs. The instruments used were the dental anxiety scale and the dental beliefs survey. The study also evaluated a Swedish version of the beliefs survey. The mean anxiety scale scores were 9.4 for emergency and 16.8 for fearful patients. The average beliefs survey item values ranged from 1.6 to 2.6 and 1.7 to 3.8 among the two groups respectively. There were clinical meaningful and statistically significant correlations between the anxiety scale and the beliefs survey. Each of the four dimensions of the beliefs survey (communication, control, belittlement and trust), also correlated with the anxiety scale of which the most clearly defined was belittlement. PMID- 8495392 TI - Oral health and dental behaviour in 11-year-old children of different ethnic groups. AB - This investigation was first, to assess the oral health of 11-year-old children in four ethnic groups in Amsterdam; second, to assess their dental behaviour and third, to identify potential determinants of frequency of toothbrushing. Representative samples of 97 Surinamese, 209 Moroccan, 128 Turkish and 102 Dutch children were examined orally and asked to complete a questionnaire. Results showed that Turkish and Moroccan children had higher mean DMFT and DMFS scores than the Surinamese and the Dutch children. The mean plaque scores in the Turkish and Moroccan children were higher than those in the other two groups. Large differences in frequency of toothbrushing were found between the four ethnic groups, the Surinamese and Dutch children claimed to be the more regular brushers. Logistic regression analysis showed that the frequency of toothbrushing was related to the children's attitude towards toothbrushing and not to parental influence. PMID- 8495393 TI - Perspectives on poor dental health and its determinants. AB - This paper is based on a cross-sectional study of 35-64-year-old Finnish adults. In the study poor dental health was defined in three ways: (1) high prevalence of dental diseases; (2) edentulousness; and (3) subjects' dissatisfaction with their dental appearance or function. The aim of the study was to determine the relationship of these conditions to certain sociodemographic background factors which are known to be associated with health. Statistical analysis was carried out by means of logistic regression analysis. The background factors associated with poor dental health varied according to the condition under consideration. Education was a factor that was associated with each of them and other associated background factors are also discussed. PMID- 8495394 TI - A study of the barriers to dental care in a sample of patients with cerebral palsy. AB - The study examined the potential barriers to dental care for a selected sample of 57 adults suffering from cerebral palsy. The majority (60 per cent) were regular dental attenders and they received dental care in general dental practice and community dental practice in almost equal numbers. Those with mobility or communication difficulties were significantly more likely to attend the community or hospital dental services (P < 0.05). Their most common perceived barriers to dental care were fear, the need to be accompanied and negative attitudes, while cost was a rarely stated barrier. A dislike of dental treatment was significantly related to irregular attendance (P < 0.05) but neither anxiety nor the need to be accompanied were significantly related to attendance pattern. PMID- 8495395 TI - Changes in the characteristics of patients attending an out-of-hours emergency dental service in Edinburgh. AB - A daily out-of-hours emergency dental service was established in Edinburgh in 1977. An analysis of some recent annual surveys carried out by the service shows that there has been an increasing trend for the patients to have experienced their dental problem for more than three days, to have travelled more than 10 miles to attend the clinic and not to have attended the dentist for more than a year. This analysis also reveals an increasing trend for people who seek treatment at the emergency service to have received routine treatment rather than emergency treatment on their last dental visit. There is evidence that the Lothian emergency dental service is developing its own clientele. PMID- 8495396 TI - Occupational stress and job satisfaction in the community dental service of north Wales: a pilot study. AB - This study was conducted to measure levels of work pressure, job satisfaction and further factors related to occupational stress in community dental service staff in north Wales. The occupational stress indicator and a modified version of the dental work stress inventory were completed by 44 community dental service staff in March 1991. The community dental service staff showed poor levels of job satisfaction and psychosomatic indicators of stress. The perception of control of the individual's working practices was highly influenced by organisational demands. The best predictor of job satisfaction was perceived control followed by work pressures. The dental surgery assistants scored more unfavourably than their dental colleagues on most measures. Dentists consider clinical matters their greatest stress while dental surgery assistants were concerned principally with their working conditions such as pay levels and working hours. The study reflects a somewhat unhappy work situation for community dental service staff which may be temporary and in response to new administrative systems being introduced. A further in-depth assessment of staff is indicated to show whether these results are situation dependent or indicate a more permanent state. PMID- 8495397 TI - An investigation into the role of post-natal health clinics in oral health education. AB - This project investigated the oral health information that was given to parents by health visitors at post-natal clinics. This issue was examined by conducting an investigation in one health district in the United Kingdom and, within that, three socially diverse locations. A questionnaire to evaluate parental oral health knowledge and awareness, as well as the personal characteristics of each respondent was developed, tested and administered to 92 respondents. This questionnaire was analysed and compared with previous studies in the same field. Few parents reported receiving oral health information from health visitors. In general, levels of knowledge reported by this sample were better than those reported for the national sample used for the 1983 child dental health survey (Todd and Dodd, 1985). However, fewer of this sample reported receiving oral health education compared to the national sample respondents. A major gap in their knowledge related to fluoride levels in water and fluoride supplements. As found in other studies this sample was also confused about the role of diet in dental caries. Recommendations are made for further improvement in the delivery and reception of oral health education in the post-natal period. PMID- 8495398 TI - The role of users in improving the quality of dental care. PMID- 8495399 TI - Hydroxylation and dealkylation of methyl-n-butylnitrosamine and role of certain cytochrome P-450 isozymes in these reactions. AB - We studied the metabolism of methyl-n-butyl-nitrosamine (MBN), a carcinogen for the rat esophagus and liver. The 2-, 3- and 4-hydroxy derivatives were identified as new metabolites of MBN. In studies on tissue slices freshly removed from MRC Wistar rats, MBN metabolism resembled that of the previously studied methyl amylnitrosamine in the esophagus catalyzed 2- and 3- hydroxylation; liver, omega 1 hydroxylation; and lung, omega-hydroxylation of both nitrosamines. Liver microsomes from Sprague-Dawley rats catalyzed 2-, 3- and 4-hydroxylation of MBN, as well as the previously studied activating reactions of demethylation and debutylation. Phenobarbital induced all five reactions of MBN bh rat liver microsomes, especially debutylation; 3-methylhol-anthrene induced 3-hydroxylation and debutylation and isoniazid induced demethylation and debutylation. Monoclonal antibodies that inhibit specific cytochrome P-450 isozymes were used to identify the isozymes involved in each reaction. Antibody 4-7-1 appeared more specific than the previously used antibody 2-66-3 for inhibiting P-450 2B1 and/or 2B2. For the metabolism of both MBN and methylamylnitrosamine by rat liver microsomes, the antibody results indicated that P-450 2C11 mainly catalyzed demethylation and omega-1 hydroxylation, P-450 1A1 or 1A2 catalyzed 3-hydroxylation and debutylation or depentylation, P-450 2E1 produced demethylation and P-450 2B1 or 2B2 produced omega-1 hydroxylation, demethylation and debutylation or depentylation. PMID- 8495400 TI - Fluorescent diagnostics of human gastric cancer and sodium fluorescein accumulation in experimental gastric cancer in rats. AB - Patients (459) with chronic gastritis, ulcers, polyposis and different types of gastric cancers were examined by endoscopic fluorescent technique using a special drug based on the sodium salt of fluorescein (F1). Eighty-five percent of gastric cancers showed positive fluorescence. The F1 distribution in the stomach of the rat with induced gastric cancer was examined. In all cases the level of F1 fluorescence in the tumor was higher than in the adjacent normal tissues of the stomach. Thus, all the obtained results confirm the selective accumulation of F1 in tumors of the stomach. PMID- 8495402 TI - Observations on the treatment of autochthonous tumors in mice with an enterovirus and cyclophosphamide. AB - Significant remissions in autochthonous mammary tumors in A/Strong mice were effected in 45% of treated animals with a vaccine prepared with an enterovirus plus cyclophosphamide. Three methods of vaccine preparation were examined. Only one was effective although all three contained viable viruses. The data are consistent with the interpretation that the effective vaccine stimulated the host reticuloendothelial (RE) system differentially so that partial destruction with cyclophosphamide resulted in the reprograming of the RE system in favor of host control. PMID- 8495401 TI - Development of a novel human extracellular matrix for quantitation of the invasiveness of human cells. AB - During the crucial stages of tumor cell invasion and metastasis, neoplastic cells must traverse extracellular matrices for their migration to distant sites. Because basement membranes (BM) serve as a critical barrier to such passages, most previous in vitro assay models have utilized either an intact BM or a reconstituted rodent or avian BM-matrix to study this process. We have created a gel-like extracellular matrix derived from human amnions which contained type IV collagen, laminin, entactin, tenascin and heparan sulfate proteoglycan. This matrix, which we called Amgel, was used to study selected steps of invasion including cell attachment to matrix, degradation of it by proteolytic enzymes and movement of human tumor cells through matrix defects. An efficient tumor invasion assay system was developed utilizing filter-supported uniform coatings of this matrix in chambers. Human tumor cells (HT-1080 fibrosarcoma and RL-95 adenocarcinoma), when seeded onto Amgel-coated membranes, attached to matrix within 2 h and initiated a time-dependent migration and invasion process, as verified by biochemical analysis and both light and electron microscopy. In an optimized invasion assay 12-15% of tumor cells completely traversed the matrix during a 72-h period with > 90% viability. In contrast to these highly-invasive cells, normal human foreskin fibroblasts and normal human endometrial stromal cells exhibited minimal migration/matrix penetration during the same time period. When the Amgel-selected tumor cells (i.e. those penetrating the barrier) were isolated, subcultured, and re-exposed to Amgel, they had heightened invasiveness (2-3-fold) as compared to the parental cells. Thus, this improved 'all human' system for quantitating the invasive ability of tumor cells may provide a valuable tool in dissecting out the mechanistic underpinnings of human metastasis. In addition, this assay has the ability to screen agents which have potential anti-invasive and by extension anti-metastatic, activity or chemotactic properties. PMID- 8495403 TI - Mutagenic activity in urine samples from female tobacco habitues. AB - Since high incidence of oral cancer in India is associated with smokeless tobacco usage, mutagenic exposure of subjects habituated to a pyrolysed tobacco product, masheri (M) and tobacco-containing betel quid (Q) was evaluated in the present study. Urinary cotinine was estimated to ascertain tobacco exposure and urine mutagenicity to Salmonella typhimurium TA98 and TA100 was used to assess mutagenic burden. Urinary cotinine levels were higher in MQ users than in M users. Urine mutagenicity was evident in control samples only upon treatment with S9, beta-glucuronidase or acidified nitrite. However, greater exposure of users to mutagens resulted in additional direct mutagenicity to TA100. PMID- 8495404 TI - Human B-cell immune response to the polymorphic epithelial mucin. AB - Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients. PMID- 8495405 TI - Effect of angiotensin II induced hypertension on tumor blood flow and interstitial fluid pressure. AB - The effect of angiotensin II-induced hypertension on tumor interstitial fluid pressure (TIFP) and tumor blood flow (TBF) was investigated to examine blood flow and pressure regulation in solid tumors. TIFP measurements were made before and after administration of angiotensin II using the wick-in-needle method in s.c. tumor implants. Relative TBF was continuously monitored by laser doppler velocimetry. The effect of host strain on TIFP was evaluated in MCA-IV mammary carcinoma, transplanted in C3H and SCID mice, and showed no significant difference. The effects of tumor types were evaluated by comparing two murine tumors, MCA-IV mammary carcinoma and FSaII fibrosarcoma, and a human tumor xenograft, LS174T adenocarcinoma, transplanted in SCID mice. Baseline TIFP was elevated in all three tumor lines to significantly different pressures. AII induced hypertension (approximately 150 mm Hg) had a variable but tumor line specific effect on TIFP and TBF. The increase in TIFP was correlated with the baseline TIFP (r2 = 0.853) (increasing from 6.9 to 8.7 mm Hg, 10.5 to 15.8 mm Hg, and 21.7 to 29.4 mm Hg in FSaII, MCA-IV, and LS174T, respectively). These data suggest that in addition to blood flow redistribution due to the steal phenomenon, arterial control of TBF and TIFP exists within these solid tumors; however, the extent of control is tumor line dependent and less than that in normal tissues. Moreover, parallel increases in TIFP and TBF do not support the hypothesis that elevated TIFP causes vascular collapse and thus decreases TBF. PMID- 8495406 TI - Specific tyrosinases associated with melanoma replicative senescence and melanogenesis. AB - Replicative senescence occurs in normal cells, in contrast to their malignant counterparts which are generally immortal in vitro. We now show that induction of melanogenesis in subconfluent B16 melanoma cells deprived of growth factors can lead to irreversible growth arrest but continued cell viability, concurrent with the expression of specific glycosylated high molecular weight tyrosinases. These tyrosinase activities identify withdrawal from the cell cycle since they were not detected in reversibly arrested quiescent melanocytes, serum-deprived melanoma, or apoptotic melanoma. Our data suggest that different tyrosinases can distinguish cycling and noncycling cells of melanocytic origin and also imply that replicative senescence can be restored in some tumor cells when induced to terminal differentiation in the absence of growth-promoting agents. PMID- 8495407 TI - Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. AB - Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Differential diagnosis of pancreatic cancer and chronic pancreatitis sometimes presents a clinical dilemma. We recently developed a highly sensitive and specific polymerase chain reaction capable of detecting 3-30 copies of mutant K-ras genes harboring codon 12 single base changes in the presence of 300,000 normal copies. Mutant ras genes were detected in DNA purified from pancreatic juice from all 6 cases of pancreatic adenocarcinoma and 1 case of intraductal papillary neoplasms of the pancreas. In 2 of 6 other cases with pancreatic adenocarcinoma, circulating metastatic cells were detected in DNA purified from peripheral blood. Activated ras genes were not found in pancreatic juice of three control cases (chronic pancreatitis and choledocholithiasis) or in the peripheral blood of two patients with insulinomas. Notable conclusions of this study are that there can be significant levels of shed tumor cells in peripheral blood and an even higher number in pancreatic juice. In addition, two different K-ras mutations were found in some patients. PMID- 8495408 TI - Characterization of insulin-like growth factor 1 in human primary brain tumors. AB - Insulin-like growth factor 1 (IGF-1) is involved in the regulation of brain development and has been suggested as an autocrine stimulator of brain tumor cell proliferation. This study demonstrates the expression of IGF-1 in tumor tissue from human gliomas and one esthesioneuroblastoma. Using immunohistochemistry, expression of an IGF-1-like peptide was localized in tumor cells of 6 of the 9 gliomas examined as well as the esthesioneuroblastoma. From one anaplastic oligodendroglioma (which showed strong IGF-1 immunostaining) the IGF-1 transcripts were characterized after isolation of mRNA followed by amplification using the reverse transcriptase-polymerase chain reaction. Two IGF-1 complementary DNAs resulting from alternative splicing of the IGF-1 primary transcript were identified. These transcripts encode two different precursor proteins which correspond to Ea IGF-1 and Eb IGF-1. The significance of IGF-1 alternative mRNA splicing pathways remains to be determined. PMID- 8495409 TI - Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. AB - Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed. PMID- 8495410 TI - Cyclophosphamide modulates rat hepatic cytochrome P450 2C11 and steroid 5 alpha reductase activity and messenger RNA levels through the combined action of acrolein and phosphoramide mustard. AB - Cyclophosphamide treatment of adult male rats leads to sustained decreases in several liver microsomal cytochrome P450 (CYP) activities, including CYP 2C11 catalyzed cyclophosphamide activation, via a process that is associated with a feminization of the overall pattern of liver enzyme expression (G. A. LeBlanc and D. J. Waxman, Cancer Res., 50:5720-5726, 1990). The present study compares the effects of cyclophosphamide and its isomeric analogue ifosphamide on the gender dependent expression of hepatic CYP 2C11 and steroid 5 alpha-reductase in adult male rats and also examines the role of the cyclophosphamide metabolites acrolein and phosphoramide mustard in feminizing the expression of these liver enzymes. Ifosphamide (a) suppressed the male-specific CYP 2C11 mRNA and CYP 2C11-catalyzed liver microsomal testosterone 2 alpha-hydroxylation and cyclophosphamide and ifosphamide 4-hydroxylation and (b) elevated the female-dominant liver enzyme steroid 5 alpha-reductase and its mRNA 7-9 days after drug treatment, both occurring in a manner similar to that of cyclophosphamide, but requiring a 50% higher dose (180 mg/kg, single i.p. injection) to achieve these effects. This pattern of response could not be achieved by treatment of rats with acrolein or with cyclophosphamide analogues that decompose to acrolein without formation of phosphoramide mustard. In contrast, phosphoramide mustard treatment (100 mg/kg) did modulate microsomal CYP 2C11 and steroid 5 alpha-reductase activities. Treatment with a lower dose (50 mg/kg) of phosphoramide mustard or with the acrolein precursor 4-hydroperoxydechlorocyclophosphamide (200 mg/kg) alone did not affect liver enzyme expression, whereas the combination of these agents produced an overall pattern of response that was similar to that conferred by cyclophosphamide. These studies establish that ifosphamide is less potent than cyclophosphamide in modulating the pattern of cytochrome P450 and steroid 5 alpha reductase expression and that phosphoramide mustard is responsible for the modulation of liver enzyme expression by cyclophosphamide, with acrolein potentiating the modulating activity of the mustard. PMID- 8495411 TI - Transplacental induction of pancreas tumors in hamsters by ethanol and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - Epidemiological studies suggest that smoking during pregnancy and passive exposure of children to cigarette smoke may increase the cancer risk in children and young adults. We have previously shown that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an active transplacental carcinogen in Syrian golden hamsters when administered by s.c. injections to pregnant females. The majority of tumors in the offspring developed in the respiratory tract. Since in smoking women the respiratory tract is the portal of entry of tobacco-related carcinogens, including NNK, we have investigated the transplacental effects of NNK given by intratracheal instillation to pregnant hamsters. The modulating effect of ethanol on the transplacental carcinogenicity of NNK in this system was also investigated because smoking and consumption of alcoholic beverages are observed in pregnant women. Our data show that exposure to NNK via the maternal respiratory tract causes a similar tumor incidence in the offspring as the s.c. route of administration. Ethanol greatly enhanced the carcinogenic response to NNK, and up to 60% of the offspring exposed in utero to ethanol and NNK developed tumors of the exocrine pancreas. PMID- 8495412 TI - Chemopreventive effect of oltipraz during different stages of experimental colon carcinogenesis induced by azoxymethane in male F344 rats. AB - Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione], a substituted 1,2 dithiole-3-thione, protects against the acute and chronic toxicities of many xenobiotics and prevents chemically induced carcinogenicity in several target organs of rodents. The effects of dietary oltipraz, fed during the initiation and postinitiation stages, on azoxymethane-induced colon carcinogenesis and on the levels of several detoxifying enzymes, namely, glutathione S-transferase, NAD(P)H:quinone reductase, and UDP-glucurinyl transferase activities, were studied in male F344 rats. At 5 weeks of age, groups of animals were fed the control diet (modified AIN-76A diet) or a diet containing 200 ppm (40% maximum tolerated dose) of oltipraz. At 7 weeks of age, all animals except those in the vehicle (normal saline solution)-treated groups were given two weekly s.c. injections of azoxymethane at a dose of 15 mg/kg body weight. Three days after the second injection of azoxymethane, the groups of animals fed the oltipraz diet were transferred to the control diet (termed the initiation period) and the groups of animals receiving the control diet were transferred to the oltipraz diet (termed the postinitiation period). All groups were continued on this regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Intestinal tumors were evaluated histopathologically using routine procedures. Liver, colonic mucosa, and tumors were analyzed for glutathione S transferase, NAD(P)H:quinone reductase, and UDP-glucurinyl transferase activities. The results indicate that oltipraz administered during the initiation stage significantly inhibited the incidence and multiplicity of invasive adenocarcinomas of the colon (P < 0.001), as well as the multiplicity of invasive and noninvasive adenocarcinomas (P < 0.01). Feeding of oltipraz during the postinitiation phase completely suppressed the formation of invasive adenocarcinomas (P < 0.0001) and significantly inhibited the formation of noninvasive and total adenocarcinomas, as well as the multiplicity (tumors/tumor bearing animal, P < 0.001). Furthermore, oltipraz significantly suppressed the tumor volume when administered during the initiation phase (> 80%) or the postinitiation (> 93%) phase. Animals fed the oltipraz diet during the postinitiation stage showed increased levels of glutathione S-transferase, NAD(P)H:quinone reductase, and UDP-glucurinyl transferase activities (2-6-fold). Although the precise mechanism by which oltipraz inhibits colon tumor initiation and/or promotion remains to be elucidated, it is likely that the effect during the initiation stage may be due to an alteration of carcinogen metabolism. PMID- 8495413 TI - Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin. AB - Prostratin and 12-deoxyphorbol 13-phenylacetate (dPP) form a new class of protein kinase C activators of unique biological activity. Although they bind to and activate protein kinase C, in mouse skin they either fail to induce typical phorbol ester (PMA) effects (e.g., hyperplasia) or induce only partial response (e.g., inflammation). Furthermore, pretreatment with these agents inhibits a range of PMA induced effects (acute and chronic hyperplasia, inflammation, etc.) These observations suggested that prostratin and dPP would function as inhibitors of phorbol ester tumor promotion. Here we verify that prediction. We report that both compounds reduced both the average number of papillomas and the tumor incidence in a tumor promotion schedule in CD-1 mouse skin, in which each PMA application was preceded by 12-deoxyphorbol 13-monoester pretreatment. The highest dose of prostratin used (2.56 mumol or 1 mg/pretreatment) caused a 96% (23-fold) reduction in the average number of papillomas with a decrease of tumor incidence from 97 to 40%. The highest dose of dPP used (21.4 nmol or 10 micrograms/pretreatment) induced an 86% (7-fold) reduction in the average number of papillomas with a 53% reduction of tumor incidence from 100 to 47%. The inhibitory effect was dose dependent. The dose causing 50% inhibition was 11 nmol/pretreatment for prostratin and 0.8 nmol/pretreatment for dPP. Maximal inhibition of tumor promotion was accompanied by a block of epidermal hyperplasia; however, significant inhibition of tumor induction was observed at doses without any apparent effect on the PMA induced hyperplasia. PMID- 8495414 TI - Effects of insulin-like growth factor receptor inhibition on human melanomas in culture and in athymic mice. AB - The role of the insulin-like growth factor (IGF) receptor in regulating the growth of melanoma cells was evaluated by examining the effect of antibody mediated IGF receptor inhibition on the growth of four human melanoma cell lines in culture and as xenotransplants in athymic mice. All four cell lines expressed typical type I IGF receptors and an antibody to this receptor (alpha IR-3) inhibited [125I]IGF-I binding. However, the cell lines varied widely in their in vitro responsiveness to IGF-I and alpha IR-3: in the WM 373 and WM 852 cell lines, IGF-I stimulated cell replication and alpha IR-3 inhibited this response, whereas in the WM 239-A and WM 266-4 cell lines neither the growth factor nor the antibody affected growth. A wide variation was also observed in the effect of the antibody on the growth of the different cell lines as xenotransplants but this qualitatively correlated with the responses observed in vitro: alpha IR-3 treatment significantly inhibited the growth of the WM 373 and WM 852 xenotransplants but did not inhibit the growth of the WM 239-A or WM 266-4 xenotransplants and may even have had a slight stimulatory effect. These results indicate that the IGF receptor pathway is a functional regulator of the in vivo growth of some melanomas and that this is reflected in the activity of this pathway as determined in vitro. These findings suggest that therapies aimed at inhibiting the IGF pathway may be beneficial in treating some melanomas. PMID- 8495415 TI - Inhibition of epidermal growth factor-like growth factor secretion in tracheobronchial epithelial cells by vitamin A. AB - Vitamin A deficiency of respiratory tract epithelium results in the phenomenon of squamous cell metaplasia. The mechanisms by which vitamin A regulates airway epithelial cell growth and differentiation are not completely understood. In this study, we focused on the effects of vitamin A (retinol) on growth of human and non-human primate tracheobronchial epithelial (TBE) cells in culture. Retinol and its derivatives have little growth-stimulatory effect on TBE cells that are maintained in primary culture in a serum-free medium supplemented with 6 hormonal supplements: insulin, transferrin, epidermal growth factor (EGF), hydrocortisone, cholera toxin, and bovine hypothalamus extract. However, it was observed that retinol exhibited dose-dependent inhibition of TBE cell growth when EGF was removed from this serum-free culture condition. This inhibition can be reversed if EGF or the conditioned medium of primary TBE cells that are maintained in vitamin A-deficient condition is added. This type of EGF-retinol interacting phenomenon was not observed with the 5 remaining hormonal supplements. Analysis of 125I-labeled EGF binding shows a down-regulation of the high affinity binding sites (Kd = 0.09 nM) on TBE cells grown in the absence of vitamin A. These results suggest that TBE cells are capable of secreting an EGF-like growth factor in the absence of vitamin A. The possibility that transforming growth factor alpha (TGF-alpha) is involved in this phenomenon is further examined by antibodies specific to TGF-alpha and its binding to an EGF-receptor. Using the TGF-alpha antibody, the presence of a TGF-alpha-specific antigen was found to be 3-fold higher in the conditioned medium obtained from the vitamin A-deficient cultures than that derived from retinol-treated cultures. Furthermore, the antibody neutralizing the TGF-alpha binding to an EGF receptor was able to reduce the DNA synthesis associated with the vitamin A deficiency. These results suggest that vitamin A plays an important regulatory role in the paracrine/autocrine secretion of EGF/TGF-alpha-like mitogen in TBE cell cultures. PMID- 8495416 TI - Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. AB - The antitumor effect of 22-oxa-calcitriol (OCT), a newly developed noncalcemic analogue of calcitriol, was examined in vivo in athymic mice implanted with human breast carcinoma with or without estrogen receptor (ER). In ER-positive MCF-7 tumor, the growth of which was dependent on exogenous estrogen, administration p.o. of OCT as well as the antiestrogen tamoxifen five times a week for 4 weeks suppressed tumor growth in a dose-related fashion. The antitumor effect of 1.0 microgram/kg body weight (BW) OCT (mean +/- SEM of tumor weight in 6 mice: 28 +/- 4% of vehicle-treated group) was comparable to that of 2.0 mg/kg BW tamoxifen (25 +/- 6% of control group). In addition, a synergistic antitumor effect of submaximal doses of OCT and tamoxifen was observed in MCF-7 tumor in vivo as well as in ER-positive breast carcinoma cell lines (MCF-7 and ZR-75-1) in vitro. Administration of OCT p.o. three times a week for 4 weeks also suppressed the growth of ER-negative MX-1 tumor in a dose-dependent manner without raising serum calcium concentrations. The antitumor effect of 1.0 microgram/kg BW OCT (mean +/- SEM of tumor weight in 10 mice: 44 +/- 6% of vehicle-treated group) was greater than that of 500 micrograms/kg BW Adriamycin (71 +/- 6% of control group). These results indicate that OCT suppresses the growth of ER-negative as well as ER positive breast carcinoma in vivo without causing hypercalcemia and that the antitumor effect of OCT can be enhanced by tamoxifen in an ER-positive tumor. It is suggested that OCT may provide a new strategy, either alone or in combination with other anticancer drugs, for systemic adjuvant therapy of breast carcinoma regardless of ER status. PMID- 8495417 TI - Molecular cloning and characterization of the complementary DNA for the M(r) 85,000 protein overexpressed in adriamycin-resistant human tumor cells. AB - An M(r) 85,000 membrane protein was identified by a monoclonal antibody MRK20 raised against an Adriamycin-resistant subline of human myelogenous leukemia K562 (K562/ADM) cells. The M(r) 85,000 protein was found to be overexpressed in both innate and acquired Adriamycin-resistant tumor lines. A complementary DNA (cDNA) clone coding for the M(r) 85,000 protein was isolated by mixed oligonucleotide primed polymerase chain reaction and further screening of a cDNA library from K562/ADM. Amino acid and nucleotide sequence analysis of the M(r) 85,000 protein revealed that this protein is identical with CD36, a cell surface adhesion molecule of endothelium, platelets, and monocytes. We constructed an expression vector utilizing two different promoters, SV40 and MMTV, and two cDNAs for the M(r) 85,000 protein that have different 3'-ends. DNA transfection experiments were carried out by the calcium phosphate method with a selectable marker using drug-sensitive human tumor lines KB3-1 and A2780 as recipient cells. We obtained transfectant clones expressing the M(r) 85,000 protein stably or inducibly but found no resistance against Adriamycin or vincristine. Direct selection with Adriamycin or vincristine or tumor cells transfected with the SV40 promoter regulated expression constructs also failed to yield drug-resistant clones. These results indicate that the M(r) 85,000 protein/CD36 cannot confer drug resistance by itself, even though the protein can be an effective marker for Adriamycin resistance. PMID- 8495418 TI - Effect of photodynamic therapy on the endothelium-dependent relaxation of isolated rat aortas. AB - The early vascular effects of photodynamic therapy (PDT) include transient vasoconstriction and platelet aggregation. Since endothelium-derived relaxing factor (EDRF) is a potent vasodilator and inhibitor of platelet aggregation, we questioned whether PDT impairs the production of EDRF. To study this possible effect of PDT, endothelium-dependent relaxations of thoracic aortas obtained from male Wistar rats were determined. The aortic rings were connected to a isometric force transducer, exposed to various doses of Photofrin porfimer sodium (Photofrin) (0.1-1.0 microgram/ml), and illuminated with red light (wavelength > 610 nm, 14.6 +/- 1.5 mW/cm2) for different time periods (5-25 min). Endothelium dependent relaxation was induced by acetylcholine in precontracted aortic rings. This EDRF-mediated relaxation was decreased after PDT in a light dose- and drug dose-dependent manner. Light microscopic examination did not show loss of endothelial cells. Similar results were obtained with rat aortas exposed to Photofrin in vivo and illuminated in vitro. Direct smooth muscle relaxation induced with sodium nitroprusside was not impaired, showing that PDT did not reduce the ability of smooth muscles to relax. No effect on the contractile responses was found either. We conclude that PDT impairs the production or release of EDRF by the endothelium. This could play an important role in the initial events occurring in vivo during and after PDT. PMID- 8495419 TI - Inhibition of urokinase by 4-substituted benzo[b]thiophene-2-carboxamidines: an important new class of selective synthetic urokinase inhibitor. AB - Urokinase-type plasminogen activator (uPA) is an important mediator of cellular invasiveness. Specifically, cell surface receptor-bound uPA activates plasminogen to the potent general protease plasmin, which then degrades extracellular matrix or basement membrane either directly or via proteolytic activation of latent collagenases. Thus, cell surface uPA initiates an extracellular proteolytic cascade with which invasive cells eliminate barriers to movement. Since cellular invasiveness plays important roles in several disease states, including cancer metastasis and invasion, arthritis and inflammation, and diabetic retinal neovascularization, the development of synthetic uPA inhibitors is an attractive therapeutic goal. Here we show that 4-substituted benzo[b]thiophene-2 carboxamidines represent an important new class of potent and selective synthetic uPA inhibitor. Two compounds in this class, B428 and B623, inhibit human uPA in plasminogen-linked assays with median inhibition concentration (IC50) values of 0.32 and 0.07 microM, respectively. This level of inhibition represents 20- and 100-fold increases in potency, respectively, relative to the 6-7 microM potencies reported for amiloride and 4-chlorophenylguanidine, the two most potent selective synthetic uPA inhibitors previously described. Importantly, both compounds show > 300-fold selectivity for uPA relative to tissue-type plasminogen activator and > 1000-fold selectivity relative to plasmin. Lineweaver-Burk analyses show uPA inhibition by B428 and B623 to be competitive in nature with inhibition constants (Ki) of 0.53 and 0.16 microM, respectively. Since it is cell surface uPA and not free or secreted uPA that is primarily responsible for cellular invasiveness, biologically effective uPA inhibitors must be capable of inhibiting cell surface uPA. B428 and B623 meet this criterion by inhibiting cell surface uPA on HT1080 human fibrosarcoma cells with IC50 values of 0.54 and 0.20 microM, respectively. Moreover, degradation of [3H]fibronectin by HT1080 cells via cell surface uPA mediated, plasminogen-dependent mechanisms is inhibited by B428 and B623, with IC50 values of 1.5 and 0.39 microM, respectively. In summary, 4-substituted benzo[b]thiophene-2-carboxamidines such as B428 and B623 represent the most potent class of competitive synthetic uPA inhibitors currently known. Their ability to selectively inhibit both free and cell surface uPA as well as cell surface uPA-mediated cellular degradative functions suggests that this class of compounds may hold significant promise for further development as antiinvasiveness drugs. PMID- 8495420 TI - Monoclonal antibody homodimers: enhanced antitumor activity in nude mice. AB - The potential for enhancing antibody potency by increasing avidity was investigated using monoclonal IgG homodimers. Chemically linked dimers were made from a human-murine chimeric monoclonal IgG (ChiBR96) which strongly binds to a variety of breast, lung, ovary, and colon carcinomas. This monoclonal antibody is capable of killing tumor cells directly without complement or effector cells in addition to mediating antibody dependent cellular cytotoxicity and complement dependent cytotoxicity. In this study, we examined the effect of antibody valency on antigen binding and biological efficacy by comparing the IgG dimer (tetravalent) to the monomeric IgG (divalent). The dimer demonstrated 3-4-fold greater binding activity against carcinoma cells than the monomer by enzyme linked immunosorbent assay. Surface plasmon resonance analyses showed that while the ChiBR96 monomer and dimer had similar rates of association on specific antigen, the dimer had a significantly slower rate of dissociation (and therefore a higher affinity constant). Although there was no difference between the monomer and dimer in antibody dependent cellular cytotoxicity and complement dependent cytotoxicity, the dimer demonstrated at least 10 times greater direct tumor cell killing than the monomer. Internalization studies using carcinoma cells pulsed with 125I-labeled antibody showed the ChiBR96 dimer reached higher intracellular levels than the monomer. The relative in vivo antitumor effects of the IgG monomer and dimer were studied in nude mice bearing human lung adenocarcinoma xenografts. The dimer was more effective in slowing tumor progression despite having a shorter serum half-life than the monomer. Increasing the valency of IgG monoclonal antibodies may be a useful approach to enhancing their biological efficacy. PMID- 8495421 TI - Phototoxicity, redox behavior, and pharmacokinetics of benzophenoxazine analogues in EMT-6 murine sarcoma cells. AB - Structural modifications to the photoinactive benzophenoxazine Nile blue A have led to three novel derivatives which include 5-ethylamino-9 diethylaminobenzo[a]phenoxazinium (EtNBA), 5-ethylamino-9 diethylaminobenzo[a]phenothiazinium (EtNBS), and 5-ethylamino-9 diethylaminobenzo[a]phenoselenazinium (EtNBSe) chlorides. The incorporation of sulfur and selenium into the benzophenoxazine moiety results in lipophilic, red absorbing (650-660 nm) chromophores which possess significantly increased singlet oxygen yields (0.025 and 0.65, respectively, compared to 0.005 for EtNBA). This study examines the photosensitizing efficacies and pharmacokinetics in vitro in the EMT-6 murine mammary sarcoma cell line as well as the physicochemical, photochemical, and redox properties of these new analogues. Comparisons with Photofrin II, the only photosensitizer available clinically, were made in an attempt to high-light their different pharmacological characteristics. The photodynamic activity of the benzophenoxazine dyes correlates with their ability to generate the phototoxin singlet oxygen and increases in the following order: EtNBA < EtNBS << EtNBSe. At an extracellular dye concentration of 0.5 microM, the light dose required to kill approximately 50% of the cells was 2.0 and < 0.5 J/cm2 for the sulfur and selenium dyes, respectively. The light dose required to kill approximately 50% of the cells for both EtNBA and Photofrin II could not be determined because of their weak phototoxic effect under these conditions. At a light dose of 3.3 J/cm2, EtNBSe is approximately 1000 times more phototoxic than Photofrin II. All three benzophenoxazine derivatives are characterized by a similar uptake/efflux pattern in vitro consisting of a rapid and extensive cellular accumulation followed by a slow efflux rate. Contrary to their rapid uptake, 50% of the accumulated EtNBS and EtNBSe is retained intracellularly after a 6-h period in dye-free medium. Video-enhanced fluorescence microscopy corroborates the rapid uptake measurements as well as indicating the intracellular localization of the dyes in both living and thermally inactivated cells. Low extracellular dye concentrations (0.05 microM) result in a punctate fluorescence pattern in the perinuclear region, while higher dye concentrations (> 0.1 microM) lead to additional fluorescence in the cytoplasm, cytomembranes, and other organelles but apparently not the nucleus. Absorption spectrometry revealed that living cells rapidly reduce the dyes to their colorless leuko form (photoinactive) if oxygen is not readily available in the environment. It is shown that the cellular reduction is an enzymatic process and that an oxygen-free and cell-free medium containing both the coenzyme NADH and the hydride transfer enzyme diaphorase is capable of reducing the dyes to the colorless leuko form.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495422 TI - Human interleukin 2 analogues that preferentially bind the intermediate-affinity interleukin 2 receptor lead to reduced secondary cytokine secretion: implications for the use of these interleukin 2 analogues in cancer immunotherapy. AB - Cancer patients undergoing interleukin (IL)-2-based immunotherapy frequently experience dose-limiting side effects believed to be caused by the actions of such cytokines as IL-1 beta, tumor necrosis factor (TNF)-alpha and -beta, and interferon-gamma (IFN-gamma). Human peripheral blood mononuclear cells (PBMC) or monocyte-depleted peripheral blood lymphocytes were stimulated for up to 7 days by either of 2 IL-2 analogues (R38A or F42K) that bind to the intermediate affinity IL-2 beta gamma receptor but have reduced abilities to bind the high affinity IL-2 receptor. We previously reported that these IL-2 analogues retain the ability to generate lymphokine-activated killing by PBMC. In this study, we analyzed the cytokine content of supernatants from stimulated PBMC and peripheral blood lymphocyte cultures by enzyme-linked immunosorbent assay. The secretions of IL-1 beta, TNF-alpha, and -beta, and IFN-gamma induced by either R38A or F42K were markedly reduced compared with secretions produced in response to recombinant wild-type IL-2. In 4 experiments, secretion was reduced an average of 39% for IL-1 beta, 57% for TNF-alpha, 83% for TNF-beta, and 86% for IFN-gamma. Polymerase chain reaction analysis of recombinant wild-type IL-2 or analogue stimulated PBMC did not reveal the presence of IL-2 mRNA; thus, differential production of endogenous IL-2 could not account for these findings. These data suggest the interaction of IL-2 and the high-affinity IL-2 receptor on human PBMC or peripheral blood lymphocyte is required for maximal secretion of IL-1 beta, TNF-alpha, TNF-beta, and IFN-gamma. Because such cytokines are believed to mediate the toxicity seen with IL-2-based immunotherapies, IL-2 analogues with reduced binding to the high affinity IL-2 receptor may prove to be an effective and less toxic means of cancer treatment. PMID- 8495423 TI - Cytokine regulation of human monocyte differentiation in vitro: the tumor cytotoxic phenotype induced by macrophage colony-stimulating factor is developmentally regulated by gamma-interferon. AB - In this study we continue our examination of the unique form of antibody dependent antitumor cytotoxicity (ADCC) which develops when human monocytes are exposed to macrophage colony-stimulating factor (MCSF) in vitro. This form of ADCC is not present in fresh monocytes and emerges only as monocytes differentiate into monocyte-derived macrophages (MDM). We now report that the presence of gamma-interferon (IFN-gamma) during this period of differentiation markedly affects the development of MCSF-induced cytotoxicity. The addition of IFN-gamma on day 0 resulted in a pronounced dose-dependent inhibition of ADCC measured on day 7 (mean inhibition, 76 +/- 12%; range, 66-94%). MDM exposed to MCSF plus IFN-gamma required 3-10-fold higher effector to target cell ratios to achieve a level of cytotoxicity comparable to that of MDM cultured with MCSF alone. This inhibitory effect was attributable to an IFN-gamma-induced shift in the basic mechanism of target cell killing, away from the phagocytic form normally seen with MCSF and toward a significantly less effective extracellular form. In order to influence ADCC, IFN-gamma had to be present prior to the onset of differentiation; if it was added later it had progressively less effect, and if it was added after differentiation was complete it was inactive. The modulatory effects of IFN-gamma also extended to a number of other developmentally regulated attributes. MDM cultured with MCSF normally acquired a characteristic morphology and immunophenotype, re-entered the cell cycle, and changed functionally from accessory cells for mitogen-induced lymphocyte activation to suppressor cells. The presence of IFN-gamma prevented the emergence of each of these attributes. Despite these negative effects, MDM exposed to IFN gamma remained viable, continued to bind and internalize MCSF, and displayed superior accessory cell function and oxidative burst activity. Taken together, our findings suggest that human monocytes are capable of following at least two distinct differentiation pathways in response to the local cytokine environment, with significant impact on the resultant macrophage phenotype in general and antitumor cytotoxicity in particular. PMID- 8495424 TI - Base transitions are the most frequent genetic changes at P53 in gastric cancer. AB - We searched for P53 mutations in gastric carcinoma by analyzing tumor DNAs from 29 patients. We detected 13 different somatic mutations in 15 patients (52%) and a biallelic polymorphism in exon 6 (5 heterozygous subjects). The somatic mutations were mainly localized in the sequences corresponding to the highly conserved domains of the protein. Twelve samples showed a single base change: 11 missense and 1 nonsense mutations. Three samples showed deletions leading to a frame shift, to the in-frame loss of 2 amino acids, and to the deletion of a splicing site. All point mutations, except one, were transitions, and 91% of them were G:C-->A:T changes. We previously analyzed this panel of tumors for allelic loss at the 17p13 chromosomal region, where the P53 gene had previously been located: the results showed an increasing incidence of allelic loss in late-stage tumors. On the contrary, in the present study no trend between P53 mutations and tumor stages was found. This observation indicates that mutation events precede allelic loss in gastric cancer. Half (54%) of the mutations occurred in samples without allelic loss, suggesting that specific mutated alleles, acting in a dominant negative fashion, can alter in vivo the P53 protein function. PMID- 8495425 TI - Transformation of NIH/3T3 cells by ornithine decarboxylase overexpression. AB - Ornithine decarboxylase (ODC) plays a rate-limiting role in polyamine biosynthesis and is intimately associated with cell proliferation and function. Although elevated levels of ODC mRNA, protein, and enzyme activity are consistently detected in transformed cells and tumors, the question remains as to whether ODC gene overexpression has a causative role in tumorigenesis. We have stably transfected NIH/3T3 fibroblasts with an expression construct containing human ODC complementary DNA under transcriptional control of the human beta-actin promoter. Cells transfected with the beta-actin/ODC DNA construct, designated NODC cells, and control transfectants, termed NLK cells, were analyzed for ODC gene expression and cell growth characteristics. ODC activity and mRNA levels were elevated 3-6-fold in NODC cells relative to NLK cells. NODC cells, in contrast to NLK control cells, are not contact inhibited, exhibit anchorage independent growth, cycle more rapidly, and induce tumors in nude mice more efficiently and rapidly. These results directly establish a causative role for the misregulation of ODC gene expression in the acquisition of a transformation phenotype and provide a model to examine the interaction of ODC and other gene products in neoplastic development. PMID- 8495426 TI - Sensitization of tumor cells to tumor necrosis factor action by the protein kinase inhibitor staurosporine. AB - Tumor necrosis factor (TNF), first described as a cytokine with tumor-necrotizing activity, is now known to be a pleiotropic molecule. The molecular mechanisms responsible for the cytotoxic activity of TNF on malignant cells are still largely unknown. In this study, we report that the protein kinase inhibitor staurosporine (56 to 1500 nM) increases about 500 times the in vitro cytotoxic activity of TNF for several murine and human tumor cell lines. Even some tumor cell lines which are resistant to TNF cytotoxicity could be sensitized to TNF killing by staurosporine. In the L929 fibrosarcoma cell line, staurosporine also enhanced the transcriptional activation of interleukin 6 synthesis by TNF (500 fold stimulation at 56 nM). At the biochemical level, staurosporine increased the TNF-mediated activation of phospholipases C and D and the transcription factor NF kappa B in L929 cells. The TNF-sensitizing effect of staurosporine does not seem to be mediated by one of the currently known staurosporine-sensitive kinases, as various other inhibitors which also inhibit one or more of these kinases were not synergistic with TNF. Interestingly, staurosporine (1 microgram) also enhanced the in vivo antitumor activity of TNF against a murine tumor model (L929 fibrosarcoma) in athymic nude mice (Swiss-nu/nu; s.c. treatment). These results suggest that TNF responsiveness of tumor cells is regulated by a novel staurosporine-sensitive target and that the combination of TNF and staurosporine may open new strategies of tumor treatment. PMID- 8495427 TI - Pathogenesis of malignant ascites formation: initiating events that lead to fluid accumulation. AB - Initiating events leading to the accumulation of malignant ascites in the peritoneal cavity were investigated in two syngeneic transplantable murine ascites-producing tumors, MOT mouse ovarian tumor and the TA3/St mammary carcinoma. The transport of two tracers, 125I-labeled human serum albumin (125I HSA) and 51Cr-labeled red blood cells (51Cr-RBC), into and out of the peritoneal cavity was studied at early times after i.p. tumor cell injection, prior to abundant fluid accumulation, and at intervals of 5 to 360 min after i.v. or i.p. tracer injection. Tracer influx and efflux rates were estimated from the mass of tracer passing into or out of the peritoneal cavity following a bolus injection of tracer into either the blood or the peritoneal cavity. Efflux of 125I-HSA from the peritoneal cavity was markedly reduced (3- to 5-fold) within 1 day of i.p. injection of either type of tumor cell. Significantly reduced efflux preceded any increase in tumor cell number and by itself did not induce peritoneal fluid accumulation. 125I-HSA tracer influx from plasma to peritoneal fluid did not increase detectably until 5 to 7 days after tumor cell injection, when the tumor cell number had increased by 10- to 100-fold. Only at relatively late stages of ascites tumor growth, when the flow rate into the peritoneal cavity had increased relative to the flow rate out of the peritoneum, was there net peritoneal fluid accumulation. Thus, increased influx, in addition to impaired efflux, were required for malignant ascites accumulation. Following i.p. injection, the efflux rates of 125I-HSA always exceeded those of 51Cr-RBC, even in ascites tumor bearing animals. Furthermore, 125I-HSA tracer disappeared from the peritoneal cavity more rapidly than it appeared in the plasma, suggesting that 125I-HSA moves more rapidly through the channels by which 51Cr-RBC egress from the peritoneum (primarily diaphragmatic lymphatics) and/or has access to additional pathways not open to 51Cr-RBC. Finally, flow rates into and out of the blood and peritoneum were used to obtain kinetic parameters that characterized tracer transport: k1, the rate constant for tracer transport from the blood to the peritoneum; k2, the rate constant for tracer transport from the peritoneal cavity to the blood; and k6, the rate constant for tracer transport from the peritoneal cavity to surrounding interstitial tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495428 TI - Culture of normal and malignant primary human mammary epithelial cells in a physiological manner simulates in vivo growth patterns and allows discrimination of cell type. AB - We cultured primary human mammary epithelial cells from five reduction mammoplasties and five breast carcinomas and attempted to improve culture conditions and define cell populations grown. Normal cells cultured on Matrigel basement membrane-like substance formed multicellular three-dimensional structures reminiscent of tissue ducts and alveoli, while malignant cells remained as single cells crawling through Matrigel much as malignant cells separate and invade basement membrane in vivo. This re-creation of normal and malignant breast cell morphology may facilitate studies of breast cancer cell biology and determination of malignant cell authenticity in culture. Growth of cells in a reduced oxygen concentration of 12% improved cell proliferation over room air (21%); however, cells could not proliferate in a completely physiological oxygen concentration of 6%, perhaps because of the medium used. We developed an improved medium for malignant cell growth, which lengthened their life span in culture, and a completely defined medium which supported cell proliferation for six passages. Methods to determine the epithelial nature of mammary epithelial cells are illustrated and discussed. The authenticity of malignant cells in culture was suggested by their proliferation without certain growth factors required for normal cell growth or with transforming growth factor beta, which arrests normal cell proliferation, and by their contact independence. PMID- 8495429 TI - Elevated high mobility group-I(Y) gene expression is associated with progressive transformation of mouse mammary epithelial cells. AB - The high mobility group (HMG) proteins I and Y are well characterized nonhistone chromosomal proteins which bind to A.T-rich regions of DNA, and may regulate gene expression and/or DNA replication. We utilized a series of mouse mammary epithelial preneoplastic and tumor cell lines to explore the relationship between neoplastic transformation and HMG-I(Y) gene expression. The cell lines used in this study were originally derived from a single hyperplastic outgrowth, and exhibit a distinct gradient of preneoplastic to highly metastatic transformation states. We measured the levels of HMG-I(Y) gene expression in these cell lines during the different phases of cell growth in culture. At both subconfluent and confluent cell densities, elevated levels of HMG-I(Y) mRNA were directly correlated with the relative degree of neoplastic transformation and metastatic progression of these cells. HMG-I(Y) mRNA levels were always highest in proliferating cells. However, the differences in HMG-I(Y) gene expression between the cell lines were greatest at confluent cell density, when the cells were not actively proliferating. HMG-I(Y) mRNA was detectable in normal primary mouse mammary epithelium proliferating in culture. However, the amount was much less than that measured in the cell lines, indicating that elevated HMG-I(Y) gene expression was also directly correlated with the conversion of normal mammary epithelium to the preneoplastic immortalized state. Southern blot analysis showed that alterations in HMG-I(Y) loci are also associated with the preneoplastic to neoplastic conversion of these cell lines, and this change may involve a gene conversion event between two different HMG-I(Y) loci. These results indicate that there is a strong correlation between elevated HMG-I(Y) gene expression and the progressive transformation of mouse mammary epithelial cells. PMID- 8495430 TI - International Symposium on Polyamines in Cancer. Critical role of polyamines in cancer: basic mechanisms and clinical approaches. PMID- 8495431 TI - Stereocontrolled synthesis of GD2. PMID- 8495432 TI - Structural study of a new sialic acid-containing O-specific polysaccharide of Salmonella arizonae O21; formation of anhydro derivatives of neuraminic acid upon treatment with anhydrous hydrogen fluoride. PMID- 8495433 TI - Stereospecific synthesis of 1,2-cis-glycosides of 2-amino sugars. PMID- 8495434 TI - All-alpha-D-linked tetra- and penta-saccharide substructures of Trestatin A by block syntheses with triflic anhydride as promoter. AB - The perbenzylated maltosyl and maltotriosyl fluorides 6 and 16 were treated with 2,3,2',3',6'-penta-O-benzyl-4,6-O-benzylidene-alpha,alpha-trehalose (7) using triflic anhydride as a promoter to give all-alpha-D-linked tetra- and penta saccharides which were finally deblocked to the free oligosaccharides 4-O-alpha maltosyl-9 and 4-O-alpha-maltotriosyl-alpha,alpha-trehaloses 18. The 1H NMR spectra of some of the compounds were fully analyzed by 1D TOCSY and ROESY experiments. PMID- 8495435 TI - Microbial synthesis of 3-deoxy-D-erythro-hex-2-ulosonic acid 6-phosphate. AB - A microbial route was explored for the synthesis of 3-deoxy-D-erythro-hex-2 ulosonic acid 6-phosphate (2-keto-3-deoxy-6-phosphogluconate, KDPG). Two strains of bacteria, Alcaligenes eutrophus H16 F34 (DSM 529) and Escherichia coli DF 71 (CGSC 4880), lacking in KDPG-aldolase activity were tested for excretion of KDPG. Using pyruvate and gluconate as carbon sources, Alcaligenes eutrophus H16 F34 accumulated and excreted 3-deoxy-D-erythro-hexulosonic acid 6-phosphate into the culture broth, while the E. coli strain, using pyruvate and glucuronate, failed. KDPG was isolated from the culture supernatant of Alcaligenes eutrophus H16 F34 in 78% yield and 5 g scale with respect to the consumed gluconate. PMID- 8495436 TI - Chemical synthesis of a comb-shaped, branched stereoregular polysaccharide, 4-O alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranan. AB - 4-O-alpha-D-Mannopyranosyl-(1-->6)-alpha-D-mannopyranan (7) was prepared via ring opening polymerization of 1,6-anhydro-2,3-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl alpha-D- mannopyranosyl)-beta-D-mannopyranose (5) using phosphorus pentafluoride as initiator in dichloromethane at -60 degrees C, followed by debenzylation. Compound 5 was obtained via glycosidation of 1,6-anhydro-2,3-O- isopropylidene beta-D-mannopyranose (1) with 2,3,4,6-tetra-O-benzyl-1-O-trichloroacetimidoyl alpha-D-mannopyran ose (2) using p-toluenesulfonic acid as catalyst and subsequent transformation of the protecting groups of the resulting 1,6-anhydro-4 O-(2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl)-2,3- O-isopropylidene-beta-D mannopyranose (3). PMID- 8495437 TI - N-Acetyl group distribution in partially deacetylated chitins prepared under homogeneous conditions. AB - The distribution of N-acetyl group in partially deacetylated chitin (DA-chitin) was investigated by nitrous acid deamination. Most deamination products of various DA-chitins (over 50% of deacetylation), prepared under homogeneous conditions, were oligomers of less than six units. These results would suggest a random distribution of N-acetyl groups in the DA-chitin molecule. PMID- 8495438 TI - Identification of 2-amino-2,6-dideoxy-D-glucose (D-quinovosamine), isolated from the cell walls of the alkaliphilic Bacillus sp. Y-25, by 500-MHz 1H NMR spectroscopy. AB - Cell walls of alkaliphilic Bacillus strain Y-25 are composed of gamma peptidoglycan and two acidic polymers. An amino sugar, which was a min component of one acidic polymer, did not correspond to any of the commercially available hexosamines. The amino sugar was isolated from the hydrolysate of the acidic polymer, purified, and identified as D-quinovosamine (2-amino-2,6- dideoxy-D glucose) by 500-MHz NMR spectroscopic analysis and polarimetry. PMID- 8495439 TI - Structural studies of Vibrio fluvialis M-940 O-antigen polysaccharide. AB - The structure of the Vibrio fluvialis M-940 O-antigen polysaccharide has been investigated by sugar and methylation analyses, specific degradations, NMR spectroscopy, and mass spectrometry. It is proposed that it consists of a heptasaccharide unit having the following structure. alpha-L-Rhap-(1-->2)-alpha-L Fucp-(1-->2)-alpha-D-Galp-(1--> 2)-alpha-L-Fucp- (1-->3)-beta-D-GlcpA-(1-->4) alpha-L-Rhap-(1-->3)-beta-D-Glc pNAc-(1--> The heptasaccharide is most probably linked to the 3-position of an alpha-D-galactopyranosyl residue in the core. PMID- 8495440 TI - Formation of alpha-(1-->6), alpha-(1-->3), and alpha-(1-->2) glycosidic linkages by dextransucrase from Streptococcus sanguis in acceptor-dependent reactions. AB - Dextransucrase from Streptococcus sanguis 10558 was found to synthesize alpha-(1- >6), alpha-(1-->3), and alpha-(1-->2) linkages during an acceptor-dependent glucosyl transfer reaction. Normally, new glucosyl residues are added at C-6 of monosaccharide acceptors. However, sugars blocked at C-6 also can serve as good acceptors. The disaccharide and trisaccharide products formed when methyl 6-bromo 6-deoxy-alpha-D-glucopyranoside was used as acceptor were isolated and characterized. Both were found to contain only alpha-(1-->3) glycosidic bonds. This supports the hypothesis that when C-6 is blocked the acceptor binds to the enzyme in a flipped orientation, resulting in an approximate exchange in space of the C-3 and C-6, thereby putting C-3 adjacent to the active site. The second alpha-(1-->3) links in the trisaccharide are formed by a single-chain mechanism without release of the intermediate disaccharide. With maltose as acceptor, new glucosyl residues are added at C-6'. However, if that position is blocked with a bromine atom, the resulting compound, 6'-bromo-6'-deoxy-maltose, can still serve as an acceptor. The product in this case was isolated and characterized. The new glycosidic link was found to be alpha-(1-->2). PMID- 8495441 TI - Purification and characterisation of a beta-D-xylosidase from the anaerobic rumen fungus Neocallimastix frontalis. AB - A beta-D-xylosidase from the anaerobic rumen fungus Neocallimastix frontalis was purified by anion-exchange and gel filtration chromatography. The enzyme was isoelectrically homogeneous and had an isoelectric point of pH 4.6. The apparent molecular mass calculated by gel filtration was 150,000 Da. Under denaturing conditions, the enzyme appeared as a dimer composed of two polypeptides with molecular masses of 83,000 and 53,000 Da. The pH and temperature optimum were 6.4 and 37 degrees C, respectively: the activity was very sensitive to temperature. The enzyme was inhibited by copper, silver and zinc ions, EDTA and SDS, and was stimulated by calcium and magnesium ions. It was competitively inhibited by D xylose with an apparent Ki of 3.98 mM. The beta-D-xylosidase exhibited hydrolytic activity on xylobiose and xylo-oligosaccharides of dp up to 7: the specific activities and maximum velocities decreased as the chain length increased. Analysis of the products of hydrolysis by HPLC indicated a typical exo-action. A mixture of beta-D-xylosidase and a xylanase acted synergistically in producing high reducing sugar values, using a xylan from oat spelts. PMID- 8495442 TI - Structure of the acidic exopolysaccharide of Pseudomonas marginalis strain ATCC 10844. PMID- 8495443 TI - Use of 2-pyridyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-beta-D glucopyranoside as a glycosyl donor and methyl iodide as an activator for the synthesis of 1,2-trans-linked saccharides. PMID- 8495445 TI - Reaction of some 1,2-trans-aldose peracetates with thionyl chloride-acetic acid- a convenient synthesis of some 1,2-trans-per-O-acetyl-D-glycosyl chlorides. PMID- 8495444 TI - A detailed 1H and 13C NMR study of a repeating disaccharide of hyaluronan: the effects of temperature and counterion type. AB - For the first time, a detailed NMR study of the conformation of methyl 2 acetamido-2-deoxy-3-O-(beta-D-glucopyranosyluronic acid)-beta-D-glucopyranoside (disaccharide 1) in aqueous solution is reported. This disaccharide is a repeating unit of hyaluronan, a polysaccharide with widespread biological and pharmaceutical applications. Relatively small changes in temperature, over typical experimental conditions (0-37 degrees C), completely change the appearance of its one-dimensional 1H NMR spectrum at 500 MHz. To determine the underlying cause for this temperature sensitivity, we analyzed 1H and 13C chemical shifts, temperature coefficients (delta gamma/delta T), 1H-1H coupling constants, and interglycosidic 1H-13C coupling constants for 1 as a function of temperature. For comparison, we measured the temperature dependence of 1H chemical shifts and coupling constants for related monosaccharides: glucuronate (GlcUA or U) and N-acetylglucosamine (GlcNAc or N), and glucose (Glc). The temperature sensitivity of the 1H spectrum of 1 is caused by relatively larger values of delta delta/delta T for some ring protons, rather than a conformational change. The effect is mediated by strong coupling. To detect the presence of long lived intramolecular hydrogen bonds in the disaccharide, we measured chemical shifts, delta delta/delta T, and coupling constants for hydroxyl protons of 1, GlcUA, and GlcNAc in 1:1 H2O-acetone-d6 at low temperature. We compared 1H NMR parameters for 1, GlcUA, and GlcNAc in water with published values measured in Me2SO-d6 and concluded that interactions with water predominated. We found no evidence for long-lived intramolecular hydrogen bonds occurring in 1 in aqueous solution. PMID- 8495446 TI - An AM1 molecular orbital study of alpha-D-glucopyranose and beta-maltose: evaluation and implications. AB - Chemical reactivity and other characteristics of alpha-D-glucopyranose and beta maltose were evaluated within a semiempirical molecular orbital (AM1) framework. Theoretically generated structures compared well to those determined by X-ray crystallographic techniques. Calculations suggested that the secondary hydroxy functions (OH-2 and OH-3) of the mono- and di-saccharides were more acidic than the primary alcohol (OH-6), which is consistent with experimental findings. In addition, the enhanced reactivity of the OH-3 locus, which is observed upon OH-2 alkylation of the object sugars, was rationalized in terms of increased OH-3 acidity. The chemical behavior of the monomers examined may be insightful in explaining the reactivity of glucopyranose polymers. PMID- 8495447 TI - Large-scale synthesis of beta-L-fucopyranosyl phosphate and the preparation of GDP-beta-L-fucose. AB - A practical 15-mmol large-scale synthesis of beta-L-fucopyranosyl dicyclohexylammonium phosphate from L-fucose in 63% overall yield was developed. The synthesis took advantage of a neighboring Bz-2 group participating in a Koenigs-Knorr-like glycosylation. The sugar phosphate was transformed into the activated sugar nucleoside, guanosine diphosphate beta-L-fucopyranose, on a gram scale. PMID- 8495448 TI - Alpha-fucosylation by 2,3,4-tri-O-benzoyl-alpha-L-fucopyranosyl bromide under Helferich conditions. PMID- 8495449 TI - The stepwise synthesis of oligo(glycosyl phosphates) via glycosyl hydrogenphosphonates. The chemical synthesis of oligomeric fragments from Hansenula capsulata Y-1842 exophosphomannan and from Escherichia coli K51 capsular antigen. AB - A stepwise approach has been used in the syntheses of pentamannosyl tetraphosphate HO-[-6Man(alpha)-PO4-]4-6Man(alpha)-OMe and tetra(N acetylglucosaminyl) triphosphate HO-[-3GlcNAc(alpha)-PO4]3- 3GlcNAc(beta) OC6H4NO2, which are fragments of the yeast and bacteria extracellular phosphoglycans. Elongation of the chain was performed with the use of suitably protected glycosyl hydrogenphosphonate derivatives for successive introduction of glycosyl phosphate residues. Partially protected monosaccharide derivatives and oligomeric blocks served as hydroxylic components. PMID- 8495450 TI - Pain induces decrease of blood flow in the common carotid arteries in cluster headache attacks. AB - Eighteen cluster headache patients and five controls were studied using ultrasound duplex techniques to measure blood flow in the common carotid arteries after nitroglycerin and placebo administration. Vessel diameter and blood flow tended to be greater before nitroglycerin in patients in the cluster headache period than in patients out of period and controls. Nitroglycerin tended to increase blood flow only in patients not in the cluster period and in controls. There was a significant decrease in common carotid blood flow and increase in vascular resistance related to maximum pain in both nitroglycerin-induced and spontaneous cluster headache attacks. Blood flow did not reach the initial flow values after the attack was over. In one patient a hyperventilation attack only temporarily decreased the pain. We suggest that the decrease in blood flow and increase in vascular resistance may be due to constriction of intracranial arteries by reflex activation of sympathetic efferents, rather than to decrease of arterial CO2 tension. PMID- 8495451 TI - SUNCT syndrome: forehead sweating pattern. AB - The forehead sweating function has been assessed in SUNCT syndrome--a short lasting, unilateral, neuralgiform headache syndrome with autonomic phenomena on the symptomatic side (conjunctival injection, lacrimation, etc.). In the three patients (of a total of six) who could be studied during paroxysms, increased evaporation was present on the symptomatic side of the forehead compared to the non-symptomatic side during attacks or to the symptomatic side between attacks. Basal sweating was generally within control limits, so long as the attack frequency was not so high as to influence the interictal level. During attacks precipitated by eating chocolate or sour apple (in the case of one of the patients), forehead sweating was also increased on the symptomatic side. The forehead sweating responses to heating and pilocarpine were without any notable or systematic asymmetries. The forehead sweating pattern in SUNCT syndrome may differ from the patterns in unilateral headaches like cluster headache, on the one hand (in which there is generally an asymmetry during heating and pilocarpine tests), and chronic paroxysmal hemicrania (CPH) and cervicogenic headache, on the other (where there is no systematic increase during attacks. PMID- 8495452 TI - A double-blind placebo-controlled trial of intranasal capsaicin for cluster headache. AB - It has been suggested that treatment of cluster headache (CH) patients with topical capsaicin may desensitize sensory neurons by depleting the nerve terminals of substance P. We attempted to determine whether capsaicin is effective in aborting CH attacks. Patients in acute cluster were randomized to receive either capsaicin or placebo in the ipsilateral nostril for 7 days. Patients recorded the severity of each headache for 15 days. Headaches on days 8 15 of the study were significantly less severe in the capsaicin group vs the placebo group. There was also a significant decrease in headache severity in the capsaicin group on days 8-15 compared to days 1-7, but not in the placebo group. Episodic CH patients appeared to benefit more than chronic CH patients. These results indicate that intranasal capsaicin may provide a new therapeutic option for the treatment of this disease. PMID- 8495453 TI - Diclofenac-K (50 and 100 mg) and placebo in the acute treatment of migraine. AB - The aim of the present study was to assess the efficacy and tolerability of single oral doses of 50 mg and 100 mg of diclofenac-K compared to placebo in migraine sufferers during three attacks. The study was conducted in a double blind, randomized, placebo-controlled, three-period, within-patient comparative trial; 72 migraine patients were treated with diclofenac-K (50 mg or 100 mg) or placebo at six centres (1 in Sweden and 5 in Finland). The primary efficacy end point was the change in pain intensity assessed on a 100 mm Visual Analogue Scale (VAS) at 120 min after taking the study medication. We found that 50 mg and 100 mg of diclofenac-K reduced the pain intensity significantly better than placebo (p = 0.003 and p = 0.001, respectively), without difference between the doses; 100 mg diclofenac-K was significantly better than placebo in improving phonophobia, photophobia, working ability and need for rescue medication. Diclofenac-K 50 mg or 100 mg is an effective and well-tolerated acute treatment for migraine headache and its associated symptoms. The higher dose of diclofenac K was only marginally more effective than the lower dose. PMID- 8495454 TI - Domperidone plus paracetamol in the treatment of migraine. AB - This study was designed to evaluate the safety and efficacy of domperidone in combination with paracetamol in the treatment of migraine. Severity of headache, duration of migraine attack and overall efficacy of treatment were amongst the variables assessed in a randomized, double-blind, three-way cross-over comparison of 1 g paracetamol plus either domperidone 30 mg, domperidone 20 mg or placebo, taken at onset of headache. Forty-six patients attending the City of London Migraine Clinic completed the study. A significant difference was observed in the duration of the migraine attack: a median of 17.5 h with paracetamol alone was reduced to 12.0 h with the addition of domperidone 20 mg, and to 12.0 h with domperidone 30 mg. No significant adverse events were reported. A reduction in pain intensity and nausea was noted but this was not statistically significant. It was concluded that domperidone shortens the duration of a migraine attack and may help reduce headache and associated symptoms. PMID- 8495455 TI - Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo controlled study. AB - Thirty patients with severe classical and common migraine participated in a double-blind placebo-controlled cross-over study of migraine prophylaxis with propranolol LA (long-acting) 80 mg once daily, or propranolol LA 160 mg once daily or placebo. Each treatment was given for two months. There were no significant differences between the three treatment periods in headache frequency, headache severity, nausea frequency or severity. There was a non significant trend for reduced duration of headache with the two doses of propranolol. The possible reasons for this negative effect are discussed. The safety of propranolol and its lack of serious side effects were demonstrated. PMID- 8495456 TI - Second cervical root neurofibroma and ipsilateral migraine headache. AB - This is a case history of a 38-year-old woman with a dumbbell-shaped C2 neurofibroma associated with right-sided classic migraine headaches (migraine with aura) and cervical trigeminal signs on the affected side. Surgical removal of the tumor was followed by resolution of the migraine headaches and persistence of the signs of cervico-trigeminal involvement. PMID- 8495457 TI - Raeder's syndrome. A case with an unusual localization. AB - We describe a patient with a Raeder's paratrigeminal neuralgia consisting of left sided frontal and orbital pain, Horner syndrome (including anhydrosis of the forehead), and sensory loss in the territory of the first division of the trigeminal nerve. The involvement of the ophthalmic nerve is not consistent with the usual localization of this syndrome to the pericarotid sympathetic plexus. Oculosympathetic and sympathetic fibers supplying the sweat glands of the forehead join the ophthalmic nerve in the cavernous plexus localized in the cavernous sinus. Therefore, this seems to be the most likely site of the lesion when the ophthalmic nerve is involved. PMID- 8495458 TI - How many different headaches do you have? AB - Patients with migraine attending a specialist clinic often have more than one type of headache. One hundred and two patients attending the City of London Migraine Clinic for the first time were asked: "What type(s) of headache do you think you have?" A separate diagnosis was made by the doctor, who was blinded to the self-diagnosis. On clinic diagnosis, 27 (26.5%) patients were found to have migraine plus an additional non-migraine headache. When compared with the self diagnosis, 15 (56%) of these had correctly self-diagnosed two types of headache. Many migraineurs can distinguish migraine from non-migraine headaches when they have both. PMID- 8495459 TI - Current controversies--abdominal migraine. PMID- 8495460 TI - Intranasal capsaicin administration. PMID- 8495461 TI - Spreading oligemia in the migraine aura--most likely an artifact due to scattered radiation. AB - The view that "spreading oligemia" reflects spreading depression in the human brain during the migraine aura is based on a defective analysis of CBF data where the most important methodological source of error (scattered radiation) has been ignored. When scattered radiation is taken into account it appears that CBF in the low flow area during the migraine aura is reduced to the ischemic level. There is no reason to believe that "spreading" of the low flow area occurs. Most likely the blood flow decreases in an area of fixed size. All available CBF evidence in fact lends support to "the vascular theory" of migraine pathogenesis. PMID- 8495462 TI - Red blood cell magnesium levels in migraine patients. AB - In the last few years, it has been suggested that magnesium plays a central role in establishing a threshold for migraine attacks and in intervening with the pathogenetic mechanisms involved in their onset. Accordingly, we determined red blood cell magnesium levels in adult migraine patients with and without aura interictally and in some of them also ictally. In comparison with normal subjects, migraineurs with and without aura had significantly lower red blood cell magnesium levels in the interictal period. Ictal red blood cell magnesium levels did not differ from the interictal values. Low red blood cell magnesium levels could be a peripheral expression of the reduced brain magnesium concentration observed in migraine patients. PMID- 8495463 TI - Changes in platelet membrane fluidity of migraine patients. AB - Platelet membrane fluidity was measured in migraine patients, with and without aura, using the fluorescent probe TMA-DPH (1-[4-(trimethylammonium) phenyl]-6 hexa-1,3,5- triene). Polarization values for TMA-DPH were significantly higher in the platelet membranes of migraine patients (with or without aura) than in those of healthy subjects. These findings signify decreased membrane fluidity and may explain some modifications in receptors, carriers or enzymes described in platelets of migraine patients. PMID- 8495464 TI - Restenosis following successful balloon valvuloplasty: bone formation in aortic valve leaflets. AB - Restenosis after balloon aortic valvuloplasty is common, occurring in as many as half or more of patients in the first year. To gain understanding of the mechanisms of restenosis we examined results of second dilatations and the histology of restenosed valves excised during valve replacement for restenosis. Eleven patients with calcific aortic stenosis underwent second valvuloplasty for restenosis. The mean age was 82 +/- 6 years. The interval between first and second dilatation was 14.7 +/- 8.5 months. First valvuloplasty resulted in an increase in valve area from 0.63 +/- 0.23 to 1.09 +/- 0.32 cm2 (p < 0.01). The valve area found after symptoms recurred was 0.56 +/- 0.18 cm2, not significantly different from the prevalvuloplasty dimensions. Second dilatation resulted in a mean aortic valve area of .76 +/- 0.22 cm2 (p = 0.011 vs results of first valvuloplasty). The change in valve area after first dilatation was 0.45 +/- 0.17 vs 0.20 +/- 0.13 cm2 after second dilatation (p < 0.01). Multiple histologic sections from excised, restenosed valves from five additional patients showed zones of active capillary and cellular proliferation and fibrosis in crevices between calcific nodules in three cases. Associated foci of ossification were seen in two of these. Stenotic nonvalvuloplasty control valves (n = 19) showed no ossifications. In conclusion, histologic changes in restenosed valves differ from those seen initially in calcific aortic stenosis, with granulation tissue, fibrosis, and ossification being present. These findings may help to explain the limited results of second dilatations for restenosis. PMID- 8495465 TI - Percutaneous mitral valvotomy using Inoue and double balloon technique: comparison of clinical and hemodynamic short term results in 350 cases. AB - The results of percutaneous mitral valvotomy (PMV) by double balloon (N = 230, Group I) and Inoue single balloon (N = 120, Group II) technique were compared. The groups were similar with respect to baseline characteristics. Following PMV there were marked symptomatic and haemodynamic benefits in both the groups. There was significant increase in mitral valve area (MVA) estimated by Gorlin's equation (Group I: from 0.83 +/- 0.18 cm2 to 2.10 +/- 0.45 cm2, p < 0.001; Group II: from 0.83 +/- 0.17 cm2 to 2.16 +/- 0.39 cm2, p < 0.001) and by echoplanimetry (Group I: from 0.84 +/- 0.18 cm2 to 1.91 +/- 0.35 cm2, p < 0.001; Group II: from 0.88 +/- 0.17 cm2 to 1.96 +/- 0.30 cm2, p < 0.001). However, the percentage increase in MVA in the two groups by echoplanimetry (Group I: 136 +/- 59; Group II: 130 +/- 51; p = NS) and by Gorlin's equation (Group I: 164 +/- 69; Group II: 168 +/- 61; p = NS) were not statistically significant. Results were considered optimal when increase in MVA was > or = 1.5 cm2, percentage increase was > or = 50, and mitral regurgitation was < 2/4. Out of 216 patients in Group I where PMV could be performed, optimal results were achieved in 184 (85.2%) by Gorlin's equation and 178 (82.4%) by echoplanimetry. In Group II, out of 116 patients, optimal results were achieved in 107 (92.2%) by Gorlin's equation and 103 (89%) by echoplanimetry. Incidence of mitral regurgitation although higher in Group II (24.1% vs. 18.9%) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495466 TI - Left main coronary angioplasty in a 10-year-old boy with homozygous familial hypercholesterolemia. AB - Homozygous familial hypercholesterolemia is a rare cause of premature coronary artery disease. A young boy with this disorder who underwent successful coronary angioplasty for left main stem stenosis is presented. PMID- 8495467 TI - Successful percutaneous mitral balloon commissurotomy in a patient with a previous mitral valve repair. PMID- 8495468 TI - Percutaneous balloon angioplasty for early postoperative modified Blalock-Taussig shunt failure. AB - Percutaneous balloon angioplasty was successful initial treatment for 2 infants who, early after operation, developed obstruction at the proximal anastomotic site of a modified Blalock-Taussig shunt. Two years later the first child had not required reoperation and the dilatation site was patent angiographically. The other baby progressed well after angioplasty but because of surgical concern about the long-term success of angioplasty, shunt surgery was repeated, the baby dying after reoperation. Angioplasty of proximal obstruction in these shunts is feasible and satisfactory long-term palliation can be achieved avoiding repeat shunt surgery before the more definitive Fontan-type procedure. PMID- 8495469 TI - Use of half of the Palmaz-Schatz stent in a stent-related dissection. AB - The placement of a Palmaz-Schatz stent may be associated with the development of a dissection and this may increase the danger of coronary thrombosis. In this case report we describe the use of half of the Palmaz-Schatz stent to cover such a dissection. The use of the half stent, by reducing the amount of metal and stent overlapping, may reduce the incidence of thrombosis and restenosis. PMID- 8495470 TI - Percutaneous treatment of post catheterization massive retroperitoneal hemorrhage. AB - We describe a patient on anticoagulant therapy with massive retroperitoneal and intraperitoneal bleeding complicating femoral catheterization. Balloon tamponade of the actively bleeding femoral artery was effective in sealing off the leakage after failed surgical exploration. PMID- 8495471 TI - Directional coronary atherectomy in a distal right coronary lesion using a shorter standard guide catheter. AB - An ulcerated and eccentric distal right coronary artery plaque was found in a 56 year-old male with post-infarction angina. The 100 cm length of present DVI (Devices for Vascular Intervention, Inc., Redwood City, CA) atherectomy guiding catheters limits the ability to reach many complex distal stenoses with the 125 cm Simpson Atherocath. After shortening the proximal portion of a standard DVI Judkins right guiding catheter without changing the distal contour, successful directional coronary atherectomy was performed. PMID- 8495472 TI - Successful directional coronary atherectomy in a patient with dextrocardia and situs inversus. PMID- 8495473 TI - Assessment of the hemodynamic significance of a left internal mammary artery graft-pulmonary artery shunt in a post-bypass patient using a Doppler-tipped guide wire. AB - We assessed the hemodynamic significance of a left internal mammary artery (LIMA) graft-pulmonary artery (PA) fistula in a post-bypass patient with chest pain. A Doppler-tipped guide wire and quantitative coronary angiography (QCA) were used to demonstrate that flow through the proximal LIMA (14.0 ml/min) was similar to the distal LIMA's contribution of flow to the left anterior descending artery (LAD) (15.6 ml/min), suggesting that the fistula was not hemodynamically significant. Therefore, intravascular Doppler and quantitative angiography may be used to assess the hemodynamic significance of a LIMA-PA fistula in a post-bypass patient. PMID- 8495474 TI - Coronary artery aneurysms: an unusual case report and a review of the literature. AB - Coronary artery aneurysms (CAA) were first recognized in postmortem studies. More recently they have been recognized in antemortem and angiographic studies and are reported to occur at an incidence of 1-2%. Left main coronary aneurysms (LMCA) are extremely rare with an incidence of 0.1%. Most of the aneurysms discovered in these angiographic studies have been in patients with cardiac symptoms of angina or acute myocardial infarction who subsequently were found to have severe narrowing of the coronary arteries. Angiographic and clinical data of a patient with a large aneurysm of the left main coronary artery and with aneurysmal disease of the thoracic and abdominal aorta are presented along with a review of the literature. PMID- 8495475 TI - New treatment approach for chronic total occlusions of saphenous vein grafts: thrombolysis and intravascular stents. AB - Balloon dilation of saphenous vein graft (SVG) occlusions has a lower success rate than angioplasty of native coronary arteries. To improve this outcome, a new therapy for chronic total SVG occlusions was developed. In three aortocoronary bypass graft patients with class III-IV angina and chronic occlusion of the SVGs to the left anterior descending artery (age of occlusions: 2-24 wk, age of graft 1-13 yr), standard recanalization was achieved with a guide wire and intracoronary urokinase infusion (0.5-1.0 million unit bolus followed by 100,000 IU/hr for 11-24 hr; mean infusion time: 19.7 hr). In each patient, a residual focal stenosis (average 82.5%) was successfully dilated and stented (single 4.0 mm Palmaz-Schatz in two patients and a 3.5 mm Strecker stent in the other). All patients had complete relief of symptoms and no sequelae. During a mean 7.7 mon follow-up, 6-mon arteriographic evaluation in two patients showed minimal intra stent narrowing (26% and 34%). In the Strecker stent patient, the device proved too small for the vein graft, leading to an 89% stent stenosis found on follow-up arteriography at 5 mon. The stent was redilated successfully with a 5% residual narrowing. After urokinase recanalization of chronic total SVG occlusions, intravascular stents may improve the long-term results seen with conventional SVG angioplasty. PMID- 8495476 TI - PTCA of "shepherd's crook" right coronary arteries with a new shape of guiding catheter. AB - Percutaneous transluminal coronary angioplasty (PTCA) of lesions in a right coronary artery with a "shepherd's crook" configuration may pose procedural difficulties due to inadequate guiding catheter back-up support. We evaluated the utility of a new shape of guiding catheter, previously evaluated for PTCA of lesions in the left coronary artery, in five cases with this particular right coronary artery anatomy. Factors responsible for success in these cases relate to the catheter's shape and construction. PMID- 8495477 TI - Tandem balloon angioplasty. PMID- 8495478 TI - Usefulness of a tracking catheter in complex coronary angioplasty. PMID- 8495479 TI - 16th Annual meeting of the Society for Cardiac Angiography and Interventions. San Antonio, Texas, May 18-22, 1993. Abstracts. PMID- 8495480 TI - Subclavian angioplasty: immediate and late results in 50 patients. AB - In order to assess the therapeutic outcome of percutaneous transluminal angioplasty for subclavian stenosis, 50 patients were followed up clinically as well as with a velocimetric Doppler after attempted angioplasty. A minimal clinical follow-up of 9 months was expected. Subclavian stenoses were due to atheroma in 49 patients and to Takayasu's disease in 1 case. Indication of angioplasty was curative in 34 (68%) symptomatic patients (posterior fossa ischemia and/or upper limb ischemia) and preventive in 16 (32%) asymptomatic patients (severe difference of blood pressure between the 2 arms and/or association with carotid stenosis or axillo-femoral bypass). Angioplasty was successful in 45 patients (primary success rate = 90%). Three (6%) thrombosis occurred due to the percutaneous approach, one of the axillary and one of the brachial artery without any significant sequelae, and one of the aorta requiring an aorto-bifemoral bypass. A complication occurred in 2 unsuccessful angioplasties (4%): an ischemic stroke occurred in 1 case and a thrombosis of the dilated site requiring a surgical bypass. Clinical follow-up over a period of 9 101 months (mean = 41) was performed in 43 out of the 45 patients who had undergone angioplasty successfully. Two patients had a follow-up shorter than 9 months: one died after 5 months, the other was lost to follow-up. By the end of the clinical follow-up, 37 (84%) out of the 44 followed-up patients had benefitted from the procedure. Doppler study performed in 35 out of the 44 followed-up patients (80%) over a period of 2-90 months (mean = 39) showed 5 restenosis (14%). This study demonstrates the good long-term results of angioplasty in case of subclavian artery stenosis. Though there are complications, angioplasty could be proposed as a first choice treatment for subclavian stenosis as compared to surgery. Indications in asymptomatic patients should be carefully weighed as complications may occur. PMID- 8495481 TI - Antigen presentation of mycobacterial peptides to human T cell clones can be immunomodulated by adding an MHC-specific inhibitor. AB - The immunomodulation of T cell recognition by mycobacterial antigens was investigated using T cell clones activated with peptide-pulsed EBV-B cells. An HLA-DR1-restricted T cell clone from a patient with tuberculosis responded to peptide 65-85 from the 65-kDa protein of Mycobacterium tuberculosis in a dose dependent manner, while no significant response was induced by antigen-nonpulsed EBV-B cells or EBV-B cells pulsed with an unrelated antigen (streptokinase/streptodornase). The observed binding to HLA-DR1 could be inhibited when the EBV-B cells were cultured in the presence of an excess of an HLA-DR1-restricted T cell epitope (residues 1-20) from the 19-kDa protein of M. tuberculosis. This inhibition was dose-dependent. In other experiments, proliferation of a DR1-restricted T cell clone from a healthy individual which responded to peptide 1-20 was inhibited by an excess of peptide 65-85, confirming that these peptides are able to compete for the same DR1-binding site. Nevertheless, the T cell clone from the healthy individual showed a relatively lower percentage of inhibition compared with the T cell clone from a patient with tuberculosis. Furthermore, the intensity of this inhibition was reversed as the concentration of stimulatory peptide was increased. The experiments described in this paper demonstrate the immunomodulation of mycobacterial antigen presentation by peptide competition at the level of MHC-binding sites. These data may be important for an understanding of the interactions involved in the mycobacterial cell-mediated immune recognition. PMID- 8495482 TI - Murine thymocytes with ability to inhibit IL-2 production. II. Characterization of a subpopulation with regulatory function in the thymus. AB - Studies were performed to characterize the thymocyte subset responsible for the efficient inhibition of spleen cell interleukin-2 (IL-2) production. By different cell separation techniques, C-mediated cytotoxicity, immunoabsorbance, and cell sorting by flow cytometry, we have identified two phenotypically distinct subpopulations of thymocytes. One subset, belonging to the minor population (3 5%) of the CD4-CD8-, i.e., double-negative thymocytes, is defined as the subset from which the suppressive thymocytes are generated. After 28 hr of Con A stimulation, these cells undergo a phenotypical change in vitro and generate a population exerting the inhibitory effect. This latter subset inhibits 95-99% of the IL-2 produced by spleen cells and is characterized by expressing the CD8 antigen, high levels of HSA, low levels of CD3, and being IL-2R positive (HSA+CD4 CD8+CD3lowIL-2R+). Based on the experiments where stimulated CD4+CD8+, i.e., double-positive thymocytes, failed to suppress IL-2 production, we conclude that the CD8+ immature single-positive thymocytes are generated directly from the DN subset as an intermediate stage to the DP cells. When CD8(+)-stimulated thymocytes were enriched, the suppression was efficient even at thymocyte:spleen cell ratio of 0.01:1. It is suggested that this subpopulation of thymocytes may serve as a regulatory set of cells during critical stages of thymic maturation. PMID- 8495483 TI - Regulation of resting and IL-2-activated human cytotoxic lymphocytes by exogenous nucleotides: role of IL-2 and ecto-ATPases. AB - In this investigation we studied the modulation of human NK- and CTL-mediated cytotoxicity in response to extracellular nucleotides. NK cell-mediated cytotoxicity (CMC) was inhibited in a dose-dependent manner by ATP/ADP, GTP/GDP, and by pentasodium triphosphate (PST), whereas MHC-restricted CTL were inhibited by GTP/GDP and PST, but not by ATP/ADP. Triphosphates were the most potent inhibitors, followed by diphosphates and monophosphates which were the least effective, suggesting that the inhibition was not due to the sugars nor adenosine and guanosine nucleotides, but rather to the increasing negative charges. Cultured CTL, fresh NK cells that had been incubated with IL-2 for 18 hr and IL-2 dependent NK 3.3 cells were all inhibited by GTP, but not by ATP. This differential regulation of fresh NK cells and CTL by exogenous nucleotides is dependent upon the presence of IL-2, but IL-4, IL-6, and IL-8 did not have any effect. Mouse CTL are resistant to ATP presumably because they contain high levels of ecto-ATPases. Different levels of ecto-ATPase activity in human CTL and NK cells may therefore explain the difference in the responses of these effector cells to extracellular nucleotides. To test this possibility we determined the levels of ecto-ATPases in human CTL and NK cells and showed that CTL contained five times more ecto-ATPases than NK cells. Incubation of NK cells with IL-2 or IL-4 did not significantly change the level of ecto-ATPase activity on NK cells. Treatment of NK cells with IL-2 also did not significantly change the substrate specificity of NK-ecto-ATPases toward the extracellular ATP and GTP. Furthermore, treatment of CTL and NK cells with a potent ecto-ATPase inhibitor, 5' fluorosulfonylbenzoyladenosine (FSBA), did not significantly alter the effect of exogenous nucleotides on the lytic potential of CTL and NK cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495484 TI - Transfection of human immunodeficiency virus type 1 proviral DNA into primary human monocytes. AB - To investigate the expression of human immunodeficiency virus (HIV) genes in human monocytes, a DNA transfection system was developed and characterized using cultured primary monocytes. Monocytes that were cultured 6-7 days in an adherent monolayer were efficiently recovered and transfected by electroporation with an expression vector containing the Escherichia coli lacZ gene under control of the cytomegalovirus immediate-early promoter. Successful transfection was detected by expression of beta-galactosidase activity and by histochemical staining for beta galactosidase in cells that were allowed to readhere to plastic following transfection. Over 30% of the surviving adherent monocytes expressed the transfected beta-galactosidase gene. In the same manner, monocytes were transfected with HIV provirus clones pIIIB and pIIB/PB. The provirus pIIIB/PB differs from pIIIB only in that it contains a small sequence from the env gene of a macrophage tropic HIV-1. Virus derived from pIIIB will not replicate in monocytes whereas virus derived from pIIIB/PB will. Monocytes transfected with either provirus DNA expressed high levels of p24 antigen within 1 day of transfection, and cell-free supernatants contained virus that was infectious for T cells. In contrast, only supernatants from pIIIB/PB transfections contained virus capable of infecting monocytes. Thus, proviral DNA of T cell tropic HIV efficiently completes the retroviral life cycle in monocytes in a manner indistinguishable from that of macrophage tropic HIV, and progeny virus retain their T cell tropism. PMID- 8495485 TI - Autoreactive MHC-restricted cytotoxic cells in BALB/c mice after novel immunisation with a conserved mammalian autoantigen. AB - We investigated whether a novel immunisation scheme using an endogenous protein could stimulate an autoreactive cytolytic response. The protein selected was porcine dihydrolipoamide dehydrogenase, the E3 component of the mitochondrial 2 OADC enzyme family, because it is structurally conserved in mammals and ubiquitously expressed. Recombinant insulin was used as an alternative antigen. Female BALB/c mice were injected with adjuvant-free syngeneic lymphoid cells that had been exposed to E3 in hypertonic medium to facilitate its pinocytosis and were given two booster injections. Effector lymphoid cells from immunised mice were cultured in vitro with irradiated syngeneic cells that had been treated with hypertonic medium, either with or without antigen. Cytolytic effector cells were detected that lysed isogeneic and not allogeneic target cells, but only from mice immunised with E3. This experimental system provides a new model for the early stages of the development of autoimmunity. PMID- 8495486 TI - Differential effects of a monoclonal antibody recognizing 3-deoxy-D-manno-2 octulosonic acid on endotoxin-induced activation of pre-B cells and macrophages. AB - A monoclonal antibody (E1), which reacts with the 3-deoxy-D-manno-2-octulosonic acid region of lipopolysaccharides belonging to the rough Re chemotype (LPS-Re) was used to analyze in vivo and in vitro effects of endotoxin. E1 inhibited LPS Re-induced activation of Z0Z/3 pre-B cells (expression of surface immunoglobulins) and mature splenic B cells (DNA synthesis) and blocked the binding of biotin-labeled LPS-Re to mouse peritoneal macrophages. However, other effects elicited by LPS-Re, such as the production of interleukin 6 and tumor necrosis factor alpha by macrophages, and the acute lethality in galactosamine sensitized mice, were not inhibited by E1. The results suggest that the specificity of the LPS receptor which triggers the production of cytokines in macrophages is different from that of the LPS receptor which induces activation of pre-B and B lymphocytes, and is also different from that of the major LPS binding sites of macrophages. This is consistent with the hypothesis that the large majority of LPS-binding sites of macrophages do not trigger cytokine production, and that the small number of "signaling LPS receptors" of macrophages have fine specificities which are different from those of B cells. PMID- 8495487 TI - Oligopeptides of three to five residues derived from uveitopathogenic sites of retinal S-antigen induce experimental autoimmune uveitis (EAU) in Lewis rats. AB - We have previously reported that microbial peptides having 3 to 6 amino acid sequence homology with uveitopathogenic peptide of retinal S-antigen (S-Ag) are capable of inducing experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. T-cells obtained from animals immunized with these microbial peptides proliferate when stimulated with S-Ag peptide in culture and vice versa. We were interested to know whether these 3 to 6 identical amino acid residues by themselves were sufficient to induce EAU in susceptible animals under optimal conditions. For this purpose we have determined the response of synthetic oligopeptides of 3 to 18 amino acid residues for their ability to indice EAU. Here, we report that small synthetic oligopeptides of 3 to 5 amino acid residues of the two uveitopathogenic peptides of S-Ag induced EAU in Lewis rats, although with a higher dose (2000 micrograms/rat) than that of the larger peptides (50 micrograms/rat). These results define the core sequences in the uveitopathogenic peptides of retinal S-Ag. PMID- 8495488 TI - Nonspecific cytotoxic cells in fish: antigenic cross-reactivity of a function associated molecule with the intermediate filament vimentin. AB - Nonspecific cytotoxic cells (NCC) in fish may lyse tumor cells and protozoan parasites in a similar fashion as their mammalian NK counterparts. Previous studies have shown that recognition and binding by NCC may be mediated by a receptor. In the present study the putative receptor or function-associated molecule (FAM) on NCC was shown to contain antigenic cross-reactivity with the mammalian intermediate filament vimentin. This was accomplished by comparing the specificity of anti-FAM monoclonal antibody 5C6 with commercially available anti vimentin mabs V9 and 13.2 and with a polyclonal anti-vimentin antiserum. Tissue distribution studies indicated that the anti-vimentin antibodies bound to significantly fewer (< 50%) anterior kidney, spleen, kidney, and brain cells than mab 5C6. These mabs, however, produced inhibition of NCC lysis of IM-9 target cells. Conditions of mab incubation (with NCC) which were previously shown to modulate NCC cytotoxicity by 5C6 also produced large increases in NCC lysis of IM 9 targets in the presence of mabs V9 and 13.2. The determinant(s) recognized by these antibodies is present on the cell membrane. Microscopic examination of nonpermeabilized or acetone-treated and antibody-stained cells demonstrated that acetone permeabilization produced a 28-32% increase in staining (due to intracellular binding) compared to the staining of viable cells. Biochemical analysis of the cross-reactive antigens was done using analytical 2D SDS-PAGE and Western blot experiments. Mab 5C6 detected a 32- to 35-kDa protein (pI 6.3-6.5) in NCC extracts. Anti-vimentin mab 13.2 recognized a 57-kDa vimentin protein which had a relatively broad pI range (pH 6.3-6.7). Mab 13.2 also cross-reacted (in the same Western blot) with the NCC receptor protein (pI = pH 6.3-6.5). These data indicate that the FAM on NCC/NK cells contain vimentin-like antigenic determinants which may function in target cell binding. PMID- 8495489 TI - Human naive T cells are preferentially stimulated by crosslinking of CD3 and CD45RA with monoclonal antibodies. AB - To analyze the role of CD45 molecules in CD3-mediated activation of T cells, we analyzed the effect of crosslinking different CD45 isoforms with mAbs on the proliferation of various T cell subsets in vitro. Crosslinking of CD3 and CD45RA molecules with the mAb 2H4 or WR16 resulted in the preferential stimulation of enriched naive (CD45RA+) T cells, whereas crosslinking of CD3 alone led to stimulation of enriched memory (CD45RO+) T cells. In contrast, proliferation of memory T cells was not enhanced by additional crosslinking with the memory T cell marker CD45RO. To induce the costimulatory effect on naive T cells, an intense crosslinking of the TcR/CD3 complex and CD45RA molecules by immobilized secondary antibody is necessary because enhanced proliferation did not occur when the antibodies were directly immobilized. The same differences in reactivity of CD45RA-enriched naive and CD45RO-enriched memory T cell subset could be shown by using a mAb to common CD45, indicating that the effects are not mediated by a particular antibody or by binding to different epitopes. The CD45RA-induced differences in proliferation of naive and memory T cells could not be abolished by the addition of exogenous IL2. In contrast, naive T cells were more responsive to exogenous IL2 than memory T cells independently of CD45RA crosslinking, indicating that IL2 is not responsible for the observed differences in T cell proliferation. PMID- 8495490 TI - Characterization and mechanisms of thymic atrophy in protein-malnourished mice: role of corticosterone. AB - The purpose of this project was to characterize changes in murine T lymphocyte subpopulations during thymic atrophy induced by protein malnutrition and to determine the role of elevated serum corticosterone in this process. A suitable animal model was generated by placing mice on protein-sufficient (PS) and protein deficient (PD) diets for 6 weeks. Body weight was monitored to determine the establishment and maintenance of malnutrition. Results obtained using PD mice indicated a direct correlation between serum corticosterone levels and thymic atrophy. Furthermore, results of the experiments using mice implanted with corticosterone-impregnated pellets indicated that corticosterone alone, at the levels observed in PD mice, induced thymic atrophy in normal mice. These results demonstrate that the thymic atrophy induced by protein malnutrition is primarily due to elevated serum corticosterone. As indicated by flow cytometric analysis, the number of cells in all thymocyte subpopulations decreased as protein malnutrition continued, possibly reflecting depletion of immature CD4-/CD8- and CD4+/CD8+ cells, ultimately resulting in loss of mature CD4+ and CD8+ cells. TCR expression by PD thymocytes, especially those with high levels of CD3, increased during the dietary period. Mice implanted with corticosterone pellets experienced severe losses of CD4+/CD8+ cells, resulting in thymocyte subpopulation and CD3 profiles more similar to those of hydrocortisone-injected mice than those of PD mice. Therefore, whereas thymic atrophy in protein-malnourished mice seems to be caused by elevated serum corticosterone, it appears that additional factors further modulate thymocyte proliferation, differentiation, and/or death in this system. PMID- 8495491 TI - Invariant chain expression similarly controls presentation of endogenously synthesized and exogenous antigens by MHC class II molecules. AB - I-Ak- and I-Ed-transfected L fibroblasts were supertransfected with cDNA coding for hen egg lysozyme (HEL) or measles virus hemagglutinin (HA). Well-defined cell culture conditions allowed us to obtain L cells with either no detectable endogenous Ii mRNA or a high level of endogenous Ii mRNA induced by serum starvation. Cells supertransfected with mouse Ii chain gene stably expressing a high level of Ii chain were also used as APC in parallel experiments. Class II presentation of endogenously secreted HEL or an ER-retained form of HEL to the HEL-specific I-Ak-restricted 3A9 T cell hybridoma was found to be strongly enhanced in cell transfectants expressing Ii chain. Similar results were obtained with the presentation of transmembrane HA to the HA-specific I-Ed-restricted TH5.143 T cell hybridoma. These findings correlate with those obtained with the presentation of exogenous HEL and HA. In addition, as reported to be the case for exogenous antigen, expression of a large amount of endogenous HA by the APC supplants the requirement for Ii chain expression in the enhancement of antigen presentation. These data demonstrate that presentation by MHC class II molecules of a given antigen, either exogenously provided or endogenously synthesized, is controlled in a similar manner by the Ii chain. PMID- 8495492 TI - A novel large granular lymphocyte-like cell isolated from IL-2-supplemented murine intestinal lamina propria lymphocyte cultures with potent inhibitory action on lymphocyte proliferation. AB - Regulation and control of the local immune system in the gut mucosa are poorly understood phenomena. Recently we observed in whole alpha-CD3-driven, IL-2 supplemented, lamina propria (LP) T cell cultures that pronounced anergy developed concomitant with the appearance of large granular lymphocyte (LGL)-like cells. The LGL-like cells did not appear in the cultures in the absence of alpha CD3 activation. These cells expressed Thy 1.2, NK1.1, AsGM1, CD3, and most often CD8 but were always negative for CD4. They exclusively required IL-2 to proliferate and survive in culture and several cell lines were established. Analysis of the regulatory ability of these cells on immune responses revealed that the gut LGL-like cells strongly inhibited T as well as B cell proliferation by releasing a soluble factor(s). Subsequent detection in the culture supernatants of cytokines with reported inhibitory properties on lymphocyte proliferation, interferon-gamma, and transforming growth factor beta correlated poorly to the inhibitory action of the supernatants. Despite the NK-like nature of these cells no or weak cytotoxic activity could be detected against Yac-1 target cells. The LGL-like cells expressed Fc receptors for IgE and demonstrated properties in EM and cytochemical analysis which resembled mucosal mast cells, but unlike such cells the LGL-like cells did not contain histamine or serotonin. The lamina propria of normal mouse small intestine was found to contain cells with morphology and staining pattern similar to those of cultured LGL-like cells, i.e., double-positive for Thy 1.2 and NK 1.1. We propose that this novel intestinal LGL-like cell, probably of T cell origin, may act as a potent suppressive cell in mucosal immune responses exerting a regulatory function on T cell activities and preventing adverse inflammatory reactions in the intestinal mucosa. Therefore, we suggest that these cells may be referred to as granulated inhibitory lymphocytes (GIL) cells. The lamina propria GIL cells exhibit many similarities to the recently described immunosuppressive decidual LGL cells in the placenta. PMID- 8495493 TI - Distinctive expression of lprcg in the heterozygous state on different genetic backgrounds. AB - Much knowledge of the etiopathogenesis of human autoimmune diseases has been obtained from the mutant mouse models carrying lpr and gld. These autoimmune genes have been regarded as autosomal recessive. The novel lymphoproliferative and autoimmune mutation lprcg is unique in its interaction with gld despite their different chromosomal locations: chromosomes 19 and 1, respectively. Both lprcg and lpr mutations are shown to be the defects in the Fas antigen gene that controls apoptosis. Evidence has been provided for the partial expression of lpr in the heterozygous state and the significant influences of background genes on lpr-induced autoimmune disorders. To investigate the expression of the heterozygous lprcg and the effects of background genes on it, anatomical, serological, and pathological manifestations were compared among lprcg/lprcg,lprcg/+, and +/+ mice on both MRL/MpJ (MRL) and CBA/KlJms (CBA) backgrounds. On the MRL background, lymph nodes (LN) and spleens of lprcg/+ were significantly larger in weight than those of +/+, but far lower than those of lprcg/lprcg mice. In accord with this, these lprcg/+ mice had intermediate levels of anti-single-stranded DNA antibodies, circulating immune complexes, and serum Igs between those of lprcg/lprcg and +/+ mice and were similar to lprcg/lprcg mice in severity of glomerulonephritis. However, accumulation of anomalous CD4-8- T cells characteristic of the lpr disease was not proved in the enlarged lprcg/+ LN. On the CBA background, the LN and spleen weight increases in lprcg/+ were statistically significant compared to +/+ mice but were minimal, being regarded as clinically insignificant. In support of this, lprcg/+ mice were not different from +/+ mice in any of the serological and pathological parameters examined. The results clearly demonstrate that the lprcg gene can function to induce autoimmune disorders in the heterozygous state on the MRL but not on the CBA background. PMID- 8495494 TI - IL-6 production in response to purified mycobacterial heat-shock proteins and to antigen 85 in leprosy. AB - IL-6 production was examined in PBMC cultures from healthy leprosy contacts and from leprosy patients stimulated with the purified mycobacterial 18-, 65-, and 70 kDa heat-shock proteins (hsp) and the secreted fibronectin-binding antigen 85 (Ag85). In lepromin-negative contacts, the 70-kDa hsp was the only antigen capable of eliciting significant IL-6 production. In lepromin-positive contacts, Ag85, the 65- and the 70-kDa hsp induced substantial IL-6 titers. IL-6 levels induced with the 70-kDa antigen were about fourfold higher than with the 65-kDa hsp or with Ag85. The 18-kDa antigen did not induce any IL-6 in these healthy contacts. PBMC from tuberculoid leprosy patients produced even more elevated levels of IL-6, and PBMC from lepromatous leprosy patients produced extremely high levels of IL-6. All antigens were capable of inducing IL-6 in leprosy patients. Highest levels were found in cultures stimulated with the 65-kDa hsp, and lowest levels were in cultures stimulated with the 18-kDa hsp. PMID- 8495495 TI - The effects of retinoic acid on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells. AB - Retinoic acid (RA) has attracted considerable attention as an agent with a broad range of physiologic and metabolic effects. The importance of RA in the susceptibility of vitamin A-deficient animals and humans to infection is well known. Initial studies from our laboratory showed that RA augmented the IgM response of cord blood mononuclear cells (CBMC) at concentrations ranging from 10(-5) to 10(-8) M, but not adult peripheral blood mononuclear cells (PBMC), to formalinized Cowan I strain Staphylococcus aureus (SAC), a T-cell-dependent polyclonal B-cell activator. In the present study, we demonstrate that RA augments the SAC-stimulated IgG synthesis of adult PBMC at very low concentrations (10(-11) to 10(-13) M) indicating that adult PBMC is 10(4) to 10(6) times more responsive to the augmenting effects of RA than CBMC. To evaluate the differences in dose-response characteristics between CBMC and adult PBMC, co-mixture experiments between T- and B-cells of CBMC and adult PBMC were performed. The dose-response characteristics of the augmenting effects of RA for a particular Ig isotype were related to the responding B-cell population. The results of an ELISA spot assay showed that the RA-induced enhancement in Ig synthesis was due to the "recruitment" of more B-cells to differentiate into Ig secreting cells. When RA was added to CBMC stimulated by EBV, a T-cell independent polyclonal activator, or to EBV-transformed B-cell clones, a small (twofold) augmentation in IgM synthesis was seen which suggested that RA may also have some direct effect on B-cells. However, if cord blood T-cells were preincubated with RA for 36 hr, washed, and added to cord blood B-cells with SAC, a 2.5- to 9-fold augmentation in IgM was obtained. These studies suggest that the principal mechanism(s) by which RA augments the Ig synthesis of SAC-stimulated cultures is mediated by the T-cell, or T-cell products, e.g., cytokines, which induces an increased proportion of B-cells to differentiate into Ig-secreting cells. RA may also have an effect, although minor, directly on B-cells. The differences in the dose-response characteristics between CBMC and adult PBMC appears to reside within the intrinsic capabilities of an Ig-producing B-cell subpopulation. PMID- 8495496 TI - The binding, internalization, and release of thymocytes by thymic nurse cells. AB - Recent studies in our laboratory have described the development of the SV40 transformed thymic nurse cell (TNC) line SVT-II2, that maintains the ability to internalize thymocytes in vitro. SVT-II2 cells were shown to bind and internalize a subset of the alpha beta TCR+, CD4+CD8+ thymocyte population exclusively. Also, SVT-II2 cells express cell surface class I and class II MHC antigens. These data are consistent with reports that suggest that TNCs may have a role in thymic education. In this report, we used scanning electron microscopy, transmission electron microscopy, and long-term video microscopy to study binding, internalization, and release of thymocytes by TNCs. The results of these experiments showed the internalization event to be selective and dynamic. The process appears to involve programmed cooperation between the two cell types that terminates with the release of selected thymocytes. Although no changes in thymocyte cell surface phenotype were detected as a result of their interaction with TNCs in vitro, over 90% remained viable after a 48-hr incubation period. PMID- 8495497 TI - Modified immunological status of anti-IL-10 treated mice. AB - We have shown that continuous treatment of mice from birth to adulthood with neutralizing anti-IL-10 antibodies leads to specific depletion of Ly1 B cells, while conventional B cells remain normal in terms of number, phenotype, and function. Extending our characterization of these animals, we show here that anti IL-10 treated mice can be distinguished from untreated or isotype control treated mice by several other criteria. Anti-IL-10 treated mice contained substantially elevated levels of circulating TNF-alpha, and in many cases circulating IL-6, and were profoundly susceptible to death by LPS-induced shock, a monokine mediated inflammatory reaction. Analysis of serum immunoglobulin levels in anti-IL-10 treated mice revealed a decrease in serum IgA levels to accompany the previously reported reduction in serum IgM, plus a striking increase in IgG2a and IgG2b levels. Further investigation of the Ly1 B cell depletion of anti-IL-10 treated mice revealed that this effect was transient as evidenced by the return of Ly1 B cells in normal numbers 8 weeks after anti-IL-10 treatment was discontinued. The Ly1 B cell depletion that occurred during anti-IL-10 treatment was found to be compensated by an increase in peritoneal T cells and granulocytes. Finally, while anti-IL-10 treated mice were unable to produce antibodies to phosphorylcholine and alpha 1,3-dextran, they developed normal antibody responses following intraperitoneal injections of TNP-Ficoll, suggesting the existence of subcategories within the family of thymus independent type II polysaccharide antigens. These data are discussed within the context of their implications for the roles of IL-10 and Ly1 B cells in the immune system. PMID- 8495498 TI - Iron augments macrophage-mediated killing of Brucella abortus alone and in conjunction with interferon-gamma. AB - Brucella abortus are Gram negative facultative intracellular bacteria, which survive and replicate in host macrophages. We have recently demonstrated that activation of macrophages with interferon-gamma increases their anti-brucella activities but does not result in elimination of intracellular brucellae. Here we demonstrate that iron-loaded macrophages have an enhanced capacity to kill or prevent replication of intracellular brucellae. Iron added bound to transferrin or as a salt, iron-nitrilotriacetate, can mediate the effect. Macrophages supplemented with iron-loaded transferrin in addition to activation with interferon-gamma can frequently eliminate the intracellular organisms by 48 hr after infection. The effect is apparent following phagocytosis of either nonopsonized or antibody-opsonized brucellae, and with both attenuated and virulent strains of B. abortus. The killing can be blocked by the hydroxyl radical scavengers mannitol and thiourea. This is consistent with the Haber-Weiss reaction, in which iron catalyzes the generation of hydroxyl radicals from hydrogen peroxide. PMID- 8495499 TI - Proliferation and functional responses of bone marrow-derived mast cells after activation. AB - To investigate the behavior of mast cells following activation we have studied IL 3-dependent mouse bone marrow-derived mast cells (BMMC). Proliferation of BMMC presensitized with IgE anti-DNP antibodies was assessed after immunological stimulation with DNP-HSA. Proliferative potential of activated BMMC, as detected by [3H]thymidine incorporation, was similar to that of control BMMC during the first 6 days after activation while on Day 9 activated cells incorporated more [3H]thymidine. Both activated and control BMMC numbers slightly decreased 3-4 days after challenge with antigen and by Day 5 started to increase, reaching a maximum at Day 9. Immunologic activation of BMMC presensitized with IgE antibodies led to a profound loss of responsiveness to rechallenge with the same antigen 2-24 hr and 3-5 days later (70-100% inhibition of beta-hexosaminidase release). After 12 days cells were still partially unresponsive (20% inhibition). On the other hand, when BMMC were incubated again with IgE prior to rechallenge, desensitization was less pronounced and was resolved by Day 12. Activation of BMMC with an optimal concentration of thrombin induced only a partial unresponsiveness upon rechallenge 2-4 hr after activation (30% inhibition of beta hexosaminidase release), while activation with calcium ionophore did not induce any desensitization. In both control and experimental BMMC cell-associated histamine remained stable for 12 days after challenge. We conclude that BMMC undergo a period of unresponsiveness which is more pronounced after immunological activation in contrast to nonimmunological ones, similarly to what previously shown for rat peritoneal mast cells. PMID- 8495500 TI - Igh-6b expression in BALB.nude mice. AB - Mice that differ at Igh loci and the reagents that permit resolution of such distinctions are powerful genetic tools for studying B cell heterogeneity. In this report, IgM-allotype-specific ELISA revealed that two of three sources of mice designated as BALB.nude express the Igh-6b (IgMb) allotype characteristic of C57BL mice. This observation serves to warn investigators that not all strains of mice designated BALB.nude express the Igh-6a (IgMa) allotype. PMID- 8495501 TI - Geometric considerations of disk repositioning procedures. AB - One approach to treatment of internal derangements of the temporomandibular joint (TMJ) is surgical remodeling and repositioning of the disk and its attachments. Nine joints exhibiting disk displacements (four histological series and five magnetic resonance imagining (MRI) series) were studied to analyze the geometrical and mechanical implications of surgical repositioning. In the central tomographic plane, for example, these cases would have required repositioning the disk 6.9 mm posteriorly (+/- 3.3 mm), removing 5.2 mm (+/- 1.6 mm) of remodeled retrodiskal tissue, and trimming 2.1 mm (+/- 2.0 mm) of disk. This suggests that from gross geometric considerations alone, there is not sufficient viable joint tissue to recommend disk repositioning as a routine procedure. PMID- 8495502 TI - Trigeminal neuralgia: typical or atypical? AB - The horrible disorder of trigeminal neuralgia has been reviewed in the medical literature for centuries. Various methods of diagnosis and treatment have been offered and yet, it has only been in the last few decades that two similar but different types of trigeminal neuralgias have been recognized. Typical trigeminal neuralgia, or tic douloureux, is by far the most recognized type, although atypical trigeminal neuralgia has recently appeared in the literature as well. It is of the utmost importance that these two neuralgias of the trigeminal nerve be accurately diagnosed as their forms of treatment are quite different. This short treatise will compare and contrast the two different types of trigeminal neuralgias, typical and atypical, and offer methods for treatment of both. PMID- 8495503 TI - Orthopedic jaw movement observations. Part I: Determination and analysis of the length of protrusion. AB - An analysis and quantitation of protrusive and retrusive mandibular movement is provided. This report is one study along with four other parts analyzing the mandibular opening movement, the transversal shift during protrusion and retrusion, the mediotrusive movement and mastication. Protrusive movements of 225 individuals (180 patients, 45 volunteers) were analyzed using computerized axiography. Investigating both asymptomatic volunteers and patients with abnormal joint mobility helps to improve evaluation of these abnormalities. With the aid of diagnostic computer software, the length of the pathways was measured and the characteristics of the curves were analyzed. An average group was defined based on the values found in asymptomatic individuals, comprising 50% of our volunteers. The interquartile range for the male volunteers was 8.79-12.27 mm for the right joint and 9.43-12.93 mm for the left joint; for female volunteers it was 8.32-10.64 mm and 9.2-11.26 mm, respectively. PMID- 8495504 TI - Occlusal contacts: vectorial analysis of forces transmitted to temporomandibular joint and teeth. AB - Despite relevant command of muscles in the chewing apparatus, occlusion of the upper/lower jaws is constrained by joints and opposing teeth. To describe this system performance, the link quadrilateral bell-crank comprised a suitable model to render vectorial analysis of forces transmitted to the masticatory system during mandibular elevation. Occlusal contacts were created in the above proposed model. No different mechanical responses in the system were found between maximum intercuspation contacts in centric occlusion as compared to long-centric reconstruction. There was a tendency for force decrease in joints and equal force distribution on dentition. Prematurities in centric relation, at least extent, and protrusive interferences produced concentration of forces at dentition and decrease of forces in the joint, while protrusive guidance tended to increase force in the joint. PMID- 8495505 TI - A comparison of traditional occlusal equilibration and immediate complete anterior guidance development. AB - Traditional occlusal equilibration has been advocated by numerous authors as a treatment modality for chronic myofascial pain dysfunction syndrome. However, treatment predictability and reliable clinical success has not been reported by all authors. Some report no correlation between occlusal contacts and chronic myofascial pain dysfunction syndrome. Recent publications and manuscripts have described a new occlusal adjustment technique which is aimed at reducing lengthy pretreatment disclusion time in mandibular excursions. This reduction in disclusion time physiologically and rapidly reduces contractile muscle activity in the masseter and temporalis muscles, which leads to the resolution of numerous chronic myofascial pain dysfunction syndrome (MPDS) symptoms. This new occlusal adjustment process is known as Immediate Complete Anterior Guidance Development (ICAGD). The purpose of this article is to describe the important differences in focus, sequence, and theory between traditional occlusal equilibration and ICAGD. PMID- 8495506 TI - Anterior repositioning appliances when used for anterior disk displacement with reduction--a critical review. AB - Anterior repositioning appliances are commonly used for treating patients with an anterior disk displacement with reduction. The goal is to regain a proper disk to condyle relationship. Several questions immediately arise: Does the absence of joint noise indicate that the disk is properly positioned over the head of the condyle? Does this anterior position promote healing of the ligaments surrounding the disk?; and, is this anterior position merely therapeutic, or should the mandible be kept in this forward position? This review of the literature is intended to explore how anterior repositioning appliances are used in temporomandibular joint dysfunction (TMD) patients. Hopefully, it will answer questions and also raise more questions about our treatment objectives when dealing with dysfunctional patients. PMID- 8495507 TI - The significance of posterior open bite after anterior repositioning splint therapy for anteriorly displaced disk of the temporomandibular joint. AB - Spontaneous posterior open bite was observed in 15 patients after the application of anterior repositioning splints in the treatment of anteriorly displaced disk. Recapture of the disk after treatment was clinically diagnosed in five patients. Arthrography performed on 10 patients with open bite revealed a completely recaptured disk in four patients, an anteriorly displaced disk without reduction in four patients, and an anteriorly displaced disk with reduction in two patients. This suggests that recapture of the disk in the correct position at mouth closing should be a major cause of the posterior open bite in patients who have a relatively short duration of locking and successful mandibular manipulation. Although the cause of posterior open bite with the persistently displaced disk is still unclear, an increase in the posterosuperior joint space by the posterior open bite appears to eventually produce favorable effects to joints with anteriorly displaced disks. PMID- 8495508 TI - Parotid gland carcinoma simulating signs and symptoms of craniomandibular disorders--a case report. AB - The following case involves a 33-year-old woman who received two accidental blows to her left temporomandibular joint (TMJ) region six months before her first visit to the Institute of Dentistry, University of Oulu. Both clinical and computed tomography (CT) examinations of this left TMJ strongly favored a diagnosis of craniomandibular disorders (CMD). However, a fine needle biopsy and an histopathological examination of the parotid gland established the final diagnosis as poorly differentiated adenocarcinoma of the parotid gland. The course of the disease was very aggressive developing several metastases, and the patient died 24 months after the diagnosis. The presence of facial nerve paralysis, especially in combination with cheek numbness in the parotid region, should have strongly suggested the possibility of such a malignancy. PMID- 8495509 TI - An organized approach for examining the orofacial pain and craniomandibular patient. PMID- 8495510 TI - The TMJ network--a support system for TMD patients. PMID- 8495511 TI - Teaching pain and stress management. PMID- 8495512 TI - Vibration of the temporomandibular joints with normal radiographic imagings: comparison between asymptomatic volunteers and symptomatic patients. AB - In order to estimate the effect of a background noise during temporomandibular joint (TMJ) vibration analysis, 40 recordings from sensors not attached to subjects and sensors attached to subjects without any jaw movement were evaluated. Both of them showed very small energy density, close to 0, throughout 0 to 600 Hz and flat frequency distributions. To evaluate the vibration energy of asymptomatic TMJs with normal joint anatomy and symptomatic TMJs with normal arthrographic imagings, 20 TMJs from 10 clinically normal and asymptomatic volunteers with bilateral normal TMJ computerized tomography (CT) scanning (N control) were analyzed at four mandibular positions. Results from intercuspal position and maximal opening were identical to the background noise. Results from closing and opening phase showed higher energy, especially below 150 Hz, than the background noise. Surface vibrations of 83 TMJs from patients with arthrographically normal imagings but having symptoms (NID) showed significantly higher energy than the N-control group above 300 Hz. When the total vibration energy (I(T)) is used to set the threshold for the separation of internal derangement, at I(T) = 2.06, the diagnostic specificity for the NID group is 75%, while the diagnostic sensitivity is 82.4% for internal derangement. At the same time, 98.3% of the N-control group was involved below the threshold. PMID- 8495513 TI - The effect of the stabilization splint on the TMJ closed lock. AB - The mandibular manipulation technique and anterior repositioning splint are considered acceptable conservative therapies for an acute temporomandibular joint (TMJ) closed lock. However, an anterior repositioning splint will result in a corresponding change in occlusion, such as posterior open-bite. Furthermore, invasive treatments such as surgery have many complications. This article describes the effect of the stabilization splint with more conservative therapies, including the manipulation technique, wherein the complications are minimal. In this study, the authors used the stabilization splint instead of the anterior repositioning splint. They obtained acceptable results, including the increase of interincisal distance, a decrease in Fricton's craniomandibular index, and a decrease in Helkimo's clinical dysfunction index. Therefore, the treatment method that is composed of a stabilization splint, manipulation, moist heat, and exercise should be considered as the first choice of treatment for TMJ closed lock, as opposed to a repositioning splint. PMID- 8495514 TI - [The basal cell nevus syndrome. Case report of a 14-year-old girl]. AB - "Basal cell naevus syndrome" (Gorlin's syndrome) is a sporadic autosomal dominant hereditary precancerous condition which affects several organ systems. The dominating clinical manifestations are multiple basal cell naevi which develop into malignant basocellular carcinoma. Further abnormalities include abnormalities of the vertebrae and ribs, odontogenic keratocysts, calcification of the falx cerebri, a special facial appearance with progeny and macrocephaly. Affected patients may develop also ovarian fibromas, fibrosarcomas, cardiac fibromas, medulloblastomas and meningiomas. Lymphatic and chylous mesenteric cysts are also frequent. In the submitted paper the authors present the case history of a 14-year-old girl with multiple naevi, histologically specified as solid, superficial and tricho-epithelial basalioma. Phenotypic manifestations, multiple keratocysts, bone abnormalities and calcifications of the falx cerebri which are detected in the girl led to the diagnosis of Gorlin's syndrome. The authors discuss the problem of cytogenetic findings (structural abnormalities, markers of mutagenicity) and possible therapy. PMID- 8495515 TI - [Detection and prevention of mental and motor disorders in childhood. 4. The group of children which were studied]. AB - The authors submit basic data on a group of cca 11,000 children included in a research project Detection and reduction of sensory and motor disorders in childhood. The children were examined at time intervals fixed in advance (when care was initiated, during the 4th, 8th, 12th and 36th month of age). The reduction of the number of children in the course of three years, commonly encountered, is smaller than in the majority of longitudinal studies. The ratio of boys and girls corresponds to the ratio in the population and the distribution of data in the investigated regions is constant. In subsequent investigations the authors will submit eventually data from prenatal and postnatal investigations. PMID- 8495516 TI - [Hyperinsulinism--a new pathogenic cause of cardiovascular diseases]. AB - Authors call attention to the insulin-resistance and following hyperinsulinism, as important and may be also the basic factor, which is determining for high cardiovascular morbidity and mortality. Authors analyze the pathogenesis of the Reaven's syndrome X, syndrome 5H and their symptoms--insulin-resistance, hyperinsulinism, hyperlipemia with obesity, hypertension and eventually hirsutism. Authors analyze the congenital and acquired factors, which influence its manifestation and so occurrence of the cardiovascular diseases in the adulthood. In the past paediatricians gave little attention to this problem because they supposed the problem as the problem of the adult medicine. We can see that full 5H syndrome is only the top of the iceberg with basis in childhood. In the prevention of the cardiovascular diseases the task of the paediatricians is therefore not substitutable and in future they need to give to the X syndrome extraordinary attention. PMID- 8495518 TI - [The computer program, Pediatr]. PMID- 8495517 TI - [Hypovitaminosis D, the osteomalacia syndrome and calcium homeokinesis in childhood]. AB - The author pays attention to hypovitaminosis D in childhood. Despite efforts to eliminate it, its estimated incidence in the first and second year of life is 5 20%. This relatively high incidence in our population as well as in other countries makes hypovitaminosis D one of the most frequent disorders of the child organism. In addition to nutrition-conditioned rickets more than 50 different diseases have been described with rachitic and osteomalatic manifestations. PMID- 8495519 TI - [Development of the First Pediatric Clinic and its professional contribution to Slovak pediatrics]. PMID- 8495520 TI - [Historical milestones in the development of cardiologic diagnosis and the cardiology team at the First Pediatric Clinic in Bratislava]. PMID- 8495521 TI - [New therapeutic approaches and evaluation of metabolic compensation in juvenile diabetes]. PMID- 8495522 TI - [Education as a part of comprehensive therapy in juvenile diabetes and therapeutic nature camps]. PMID- 8495523 TI - [Anorexia nervosa in pediatric practice]. PMID- 8495524 TI - [The polymerase chain reaction as a new method in molecular genetics for use in clinical diagnosis]. PMID- 8495525 TI - [Comments on the article by P. Janovsky, "Exanthema subitum--sixth disease". PMID- 8495527 TI - [The Czech Society for the Protection of Children]. PMID- 8495526 TI - [Comments on sonographic screening of upper urinary tract obstruction and approaches to its resolution]. PMID- 8495529 TI - [Is non-maternal behavior increasing?]. PMID- 8495528 TI - [The founding of the Williams Syndrome Society]. PMID- 8495530 TI - [Electrophoresis of alkaline phosphatase isoenzymes--the key to rapid diagnosis in transient hyperphosphatemia]. AB - Using the method of electrophoretic separation of isoenzymes of serum alkaline phosphatase the authors confirmed the diagnosis of transient hyperphosphatasaemia in nine children examined in the out-patient department or hospitalized with various diagnoses in the Childrens Hospital. The typical isoenzyme picture was formed by an atypical anodal fraction and the probable bone isoenzyme corresponding to the cathodal fraction. The examination method used made it possible to differentiate rapidly and relatively simply transient hyperphosphatasaemia from other diseases associated with a high serum alkaline phosphatase activity. PMID- 8495531 TI - [Pathologic karyotypes in autopsy material]. AB - In 1986-1989 the authors were concerned with the cultivation of necroptic material. Material was collected from five indication groups outlined in advance. A total of 231 specimens of necroptic material were cultivated, incl. 143 specimens subjected to cytological evaluation. From the above material 20 pathological karyotypes were diagnosed. The results of cytogenetic analysis of chromosome abnormalities were compared with the clinical and pathological diagnosis. Post-mortem chromosome analysis is important for elucidation of the aetiopathogenesis of perinatal deaths and for a comprehensive approach to families with genetic risk. PMID- 8495532 TI - [Dietary therapy of infant colic: a double-blind study]. AB - The possible role of cow's milk intolerance in the aetiology of infantile colic was assessed in 19 infants in a town either by a health worker or family doctor. Modified standard preparations of cow's milk were compared for a period longer than three weeks with soya milk preparations in a double blind experiment. On soya mild the persistence of colic syndromes was significantly reduced within one week (p < 0.01) in 11 of 19 infants meeting the diagnostic criteria for cow's milk intolerance. Four children were the symptoms did not improve spontaneously nor after soya milk were given milk with hydrolyzed protein, in two the positive response was confirmed by exposure tests. Thus in 13 of 19 infants (88%) symptoms of infantile colic disappeared almost completely after the dietary change. PMID- 8495533 TI - [Renal venous thrombosis in neonates]. AB - The authors present an account on a neonate with dextro-lateral renal venous thrombosis. They focus attention on the diagnostic and therapeutic procedure and compare it with available data from the literature. Contrary to data in the literature, they did not observe in the acute stage of renal venous thrombosis signs of disseminated intravascular coagulation in peripheral blood. It did not prove possible to elucidate the action of any of the factors leading to the development of renal venous thrombosis. After evidence of permanent functional loss of the right kidney nephrectomy was performed. Histopathological examination provided evidence of obliterating thrombosis of the renal veins with partial recanalization and calcifications. The authors emphasize the necessity of early diagnosis of renal venous thrombosis and adequate treatment based on the revealed findings. PMID- 8495534 TI - [Treatment of hypogonadism in childhood]. AB - Specificity of therapeutic approaches to hypogonadism in childhood and the need of high standard hormonal preparations are stressed. Male hypogonadism can in rare instances be treated even during infancy. Therapy of hypogonadism during puberty is, however, more common. The general rule for therapy of pubertal hypogonadism is to mimic physiological puberty, i.e. to begin with small doses and slowly increase them gradually to reach the level of adult dosage within 4-5 years. PMID- 8495535 TI - [Differential diagnosis of childhood depression]. AB - In the introduction the author summarizes general aspects of classification of depression in childhood, as depression in this age group is not a single nosological unit. The classification takes into account the character of fluctuations of mood and the course of the disease. The difficulties associated with the diagnosis of childhood depression, however do not pertain to the accurate classification of different types of childhood depression but in the first place they concern the correct diagnosis of depression and differentiation from other diagnostic unit--psychiatric and paediatric ones. The latter comprise in particular psychosomatic complaints of different types which in practice cause greatest difficulties when establishing the correct diagnosis of childhood depression. Early diagnosis is essential for optimal therapy of the acute condition as well as with regard to the long-term prognosis of mental health, disease or disorders in adult age. PMID- 8495536 TI - [Bronchomotor tests in childhood]. AB - The authors present a review of bronchoconstriction and bronchodilation tests which can be used in the diagnosis of respiratory diseases in children. Basic procedures and principles of evaluation are given. PMID- 8495537 TI - [The discovery of Pneumocystis pneumonia and Czechoslovak pediatrics]. AB - The author reviews the problem of pneumocystic pneumonia from the paediatric aspect. Assessment of the cause of interstitial plasmacellular pneumonia is in the author's opinion one of the greatest discoveries of our medicine and parasitology in this century. Pneumocystic pneumonia is in recent years of special importance in particular in treatment of impaired immunity. PMID- 8495538 TI - [The thoracic aorta--the key to many clinical entities]. PMID- 8495539 TI - [Neonatal care in the department of neonatology at the First Pediatric Clinic]. PMID- 8495540 TI - [Pediatric rheumatology in Slovakia since 1958]. PMID- 8495541 TI - [Diagnostic, therapeutic and prognostic criteria of diffuse connective tissue diseases and related entities]. PMID- 8495542 TI - [Screening and therapeutic approaches in anomalies of the uropoietic system in neonates]. PMID- 8495543 TI - [The DiGeorge syndrome]. PMID- 8495544 TI - Regulation of magnesium uptake and release in the heart and in isolated ventricular myocytes. AB - Perfused rat hearts release or accumulate approximately 10% of total Mg2+ content when stimulated with norepinephrine (NE) or carbachol, respectively. Collagenase dispersed rat ventricular myocytes increase or decrease total cell Mg2+ by 1 mM within 5 minutes when stimulated with these same transmitters. Measurements of Mg2+ transport using 28Mg or atomic absorbance spectrophotometry indicate that the rate and the extent of both stimulated Mg2+ efflux and influx are independent of the concentration of extracellular Mg2+ (0 to 1.2 mM). Mg2+ release induced by NE is rapidly reversed by the addition of carbachol, and Mg2+ uptake induced by carbachol is reversed by NE. Decreasing extracellular Na+ or Ca2+ decreases or abolishes Mg2+ efflux from myocytes. Cd2+ or other Ca2+ channel blockers also inhibit Mg2+ efflux in the presence of a physiological concentration of extracellular Ca2+. Replacement of extracellular Ca2+ with Sr2+ or with Mn2+ decreases or abolishes both stimulated efflux and influx of Mg2+. Redistribution of 85Sr in myocytes and in the supernatant indicates that under those conditions Sr2+ is released or accumulated by NE or carbachol in a manner similar to that of Mg2+. Hence, at least in the case of Sr2+, the inhibition of Mg2+ fluxes can be explained by the transport of Sr2+ rather than Mg2+ through the transport(s) systems. By contrast, replacement of extracellular Ca2+ with Ba2+ inhibits stimulated Mg2+ uptake but not Mg2+ release. These results indicate that cardiac myocytes have a major pool of Mg2+ that can be rapidly mobilized upon hormonal stimulation. The net uptake and release of Mg2+ are quantitatively similar and appear to be independent of the extracellular Mg2+ concentrations but are affected, to various degrees, by the presence of other cellular or extracellular cations. PMID- 8495545 TI - Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats. AB - To determine the effects of acute myocardial infarction on the regulation of angiotensin II (Ang II) receptors and contractile performance of left and right ventricular myocytes, coronary artery ligation was surgically induced in rats, and Ang II receptor density and affinity and the mechanical properties of surviving muscle cells were examined 1 week later. Physiological determinations of cardiac pump function revealed the presence of ventricular failure, which was associated at the cellular level with a depression in the velocity of myocyte shortening and relengthening, a prolongation of time to peak shortening, and a reduction in the extent of cell shortening. These abnormalities in single-cell function were more prominent in left than in right ventricular myocytes. Cellular hypertrophy was documented by increases in cell length and width, which were also greater in the spared myocytes of the infarcted left ventricle. Reactive hypertrophy was accompanied by a 1.84- and 1.85-fold increase in the density of Ang II receptors on left and right myocytes, respectively. On the other hand, the affinity of Ang II receptors for the radiolabeled antagonist was not altered. However, Ang II-stimulated phosphoinositol turnover was enhanced by 3.7- and 2.5 fold in left and right myocytes, respectively, after infarction. Ventricular myocytes were found to possess the AT1 receptor subtype exclusively. In conclusion, myocardial infarction leads to impairment in the contractile behavior of the remaining cells and to the activation of Ang II receptors and effector pathway associated with these receptors, which may be involved in the reactive growth adaptation of the viable myocytes. PMID- 8495546 TI - Regulation of diacylglycerol metabolism by vasoconstrictor hormones in intact small arteries. AB - The initiation of receptor-mediated small artery contraction is dependent on inositol 1,4,5-trisphosphate-stimulated release of stored calcium. The role of the other product of inositol lipid hydrolysis, 1,2-diacylglycerol, in maintaining contraction remains controversial. Therefore, we have determined the contractile response of rat subcutaneous small arteries (< 300 microns i.d.), when mounted as ring preparations in a myograph, to noradrenaline, angiotensin II, KCl-induced membrane depolarization, and a cell-permeable diglyceride, dioctanoylglycerol. In parallel experiments, the conversion of this diglyceride to dioctanoylphosphatidate was studied in 32P-labeled vessels. Dioctanoylglycerol produced a slow-onset sustained contraction that was dependent on extracellular calcium. This was accompanied by the generation of the lipid dioctanoylphosphatidate. Noradrenaline and KCl induced rapid-onset sustained contractions and increased the production of dioctanoylphosphatidate (75% and 91%, respectively). In addition, dioctanoylglycerol levels were reduced (41%) after noradrenaline stimulation, suggesting activation of diacylglycerol kinase. In contrast, the contractile response to angiotensin II was transient, and this agonist did not significantly affect the conversion of dioctanoylglycerol to phosphatidate. Noradrenaline markedly increased (fourfold) the formation of endogenous phosphatidate, whereas endogenous 1,2-diacylglycerol was increased (47%) with angiotensin II. These results demonstrate that phosphatidate formation is regulated by vasoconstrictor hormones during receptor-mediated contraction, independent of diglyceride mass. Modulation of the levels of lipid second messengers downstream from phospholipid hydrolysis may represent a mechanism by which agonists that act through the same signaling system produce different contractile responses. PMID- 8495547 TI - Vascular exchange in the kidney. Regional characterization by multiple indicator tomography. AB - In previous work with the method of multiple indicator dilution (MID), we have established that a spatially distributed model of transcapillary exchange proposed by Goresky, Ziegler, and Bach (GZB) accurately describes, at the in vivo whole-organ level, the handling of extracellular indicators in the canine renal cortex. To date, however, it has not been possible to assess the key hypothesis that GZB corresponds to the actual local mechanism of exchange in vivo and is not just a compact summary of the kidney's average whole-organ behavior. By adapting the MID method to high speed computed tomography (CT), we are now able to report that the GZB mechanism is an accurate description of renal cortical transcapillary exchange down to volumes of cortical tissue comprising no more than a few per cent of the total cortical mass, i.e., containing no more than a few thousand nephrons. A small bolus of iohexol (radiopaque extracellular indicator) or iodipamide ethyl ester microparticles (radiopaque plasma indicator) injected into the renal artery was followed by CT as it passed through the kidney and into the renal vein. Time-attenuation value curves of the two contrast media obtained from the renal vein and from regions of interest in the cortex were then modeled with the GZB mechanism and with a more complex formulation that includes GZB as a limiting case. When applied to the data, the models converged to GZB as the best fit for each region examined. The GZB mechanism is found to provide excellent agreement with the regional data. PMID- 8495548 TI - Platelets protect against myocardial dysfunction and injury induced by ischemia and reperfusion in isolated rat hearts. AB - Platelets are a source of vasoactive mediators that regulate vascular tone. Platelets also play a role in intravascular thrombus formation and dynamic coronary constriction that result in myocardial ischemia. However, effects of platelets on myocardial function after ischemia and reperfusion are unknown. In this study, we examined the effects of platelets on myocardial dysfunction caused by ischemia/reperfusion. Buffer-perfused isolated rat hearts, after global ischemia (15 minutes) and reperfusion (10 minutes), developed marked myocardial dysfunction, indicated by a 65 +/- 4% decrease in the force of cardiac contraction (FCC) and a 26 +/- 7% increase in coronary perfusion pressure (CPP). Ischemia/reperfusion was also associated with release of creatine kinase (CK) and ATP metabolites in the coronary effluents. Perfusion of hearts with buffer containing washed rat platelets (3-8 x 10(7) cells/ml) protected hearts against dysfunction from ischemia/reperfusion, indicated by minimal changes in CPP (-1 +/ 1%) and FCC (-1 +/- 3%). Release of CK in the coronary effluent was also reduced, as was the release of ATP metabolites in the platelet-perfused hearts. Perfusion of hearts with serotonin receptor antagonist LY53,857 (10(-6) M), thromboxane A2 receptor antagonist SQ29,548 (10(-6) M), adenine nucleotide scavenger apyrase (0.4 units/ml), or nitric oxide synthetase inhibitor NG monomethyl-L-arginine (2 x 10(-4) M) attenuated (p < 0.05) the platelet-mediated cardioprotective effects. Perfusion of the hearts with L-arginine (2 x 10(-4) M) instead of platelets also showed modest protective effects on FCC (-4.3 +/- 13%), CPP (+18 +/- 7%), and CK release. Prolongation of the ischemic period to 30 minutes and reperfusion to 20 minutes also demonstrated marked cardiac dysfunction (FCC, -58 +/- 10%; CPP, +36 +/- 8%) in buffer-perfused hearts. Perfusion of hearts with platelets in this setting of prolonged ischemia/reperfusion also exhibited protective effects on FCC (-24 +/- 10%), CPP (+12 +/- 6%), and CK release. Thus, platelets protect myocardium from ischemia/reperfusion-induced injury, and these protective effects of platelets are evident regardless of the duration of ischemia/reperfusion. Furthermore, these cardioprotective effects of platelets seem to be related to the release of serotonin, thromboxane A2, and adenine nucleotides. These substances most likely elicit release of endothelium-derived relaxing factor, with its attendant tissue protective effects, from the microvascular endothelium of hearts. PMID- 8495549 TI - Extracellular Ca(2+)-dependent potentiation by cocaine of serotonin- and norepinephrine-induced contractions in rat vascular smooth muscle. AB - Using front-surface fluorometry, we determined the effects of cocaine on force and cytosolic Ca2+ concentration ([Ca2+]i) in the rat aorta. We also examined the effects of cocaine on 45Ca2+ influx. Cocaine (10(-7) to 10(-4) M) alone did not alter the resting level of [Ca2+]i and force. Cocaine (< 10(-4) M), in a concentration-dependent manner, potentiated the 10(-6) M serotonin (5-HT)-induced or 10(-8) M norepinephrine (NE)-induced sustained increase in [Ca2+]i and force in the presence of extracellular Ca2+, whereas it had no potentiating effects in Ca(2+)-free solution. Similar potentiating effects of cocaine were observed in pharmacologically denervated strips. Cocaine (10(-5) M) produced a leftward shift of concentration-response curves for both 5-HT- and NE-induced increases in [Ca2+]i and force with no effect on the maximal response or the relations between [Ca2+]i and force. Cocaine (10(-5) M also accelerated the 45Ca2+ influx during activation by 10(-6) M 5-HT or by 10(-8) M NE. Cocaine (> 10(-3) M) inhibited 5 HT-, NE-, and high-K+ depolarization-induced contractions accompanied by decreases in [Ca2+]i in normal physiological salt solution and 5-HT- or NE induced transient increase in [Ca2+]i and force in Ca(2+)-free physiological salt solution. Thus, low concentrations of cocaine potentiate NE- or 5-HT-induced contraction by augmenting the increase in [Ca2+]i. These potentiating effects may derive from either an increase in the affinity of the receptors to agonists or an increase in the Ca2+ influx. On the other hand, high concentrations of cocaine (> 10(-3) M) have a relaxant effect on vascular smooth muscle, as a result of a decrease in [Ca2+]i. PMID- 8495550 TI - Distinct behavior of cardiac myosin heavy chain gene constructs in vivo. Discordance with in vitro results. AB - Transcriptional thyroid hormone responsiveness of the cardiac alpha-myosin heavy chain (alpha-MHC) gene has been demonstrated in transfections into fetal and neonatal cardiomyocytes and in transgenic mice. However, the correspondence between the regulation of MHC expression in dissociated cells with that in the intact heart is unclear. Given the cost and time involved in generating multiple transgenic lines for the characterization of gene regulatory elements, we used direct cardiac gene transfer to identify elements regulating both basal and thyroid hormone responsive cardiac alpha-MHC gene expression in the adult heart in vivo. Sequences upstream of the rat alpha-MHC gene linked to a luciferase reporter gene were injected into the hearts of adult rats subjected to various thyroid manipulations. The 161-bp sequence upstream of the transcription start site, which contains a TATA box, a CCAATT box, and a thyroid hormone response element, was transcriptionally active but not thyroid hormone responsive. The expression of a construct containing 388 bp of upstream sequence was increased by thyroid hormone administration, a response that required an intact thyroid hormone response element. However, expression of this construct failed to decrease to basal levels in a hypothyroid state. To confer complete (positive and negative) thyroid hormone regulation, 2,936 bp of upstream sequence was sufficient. These results demonstrate that, although necessary, the thyroid hormone response element is not sufficient for complete thyroid hormone regulation of this gene in vivo. In addition, DNA sequences regulating the quantitative expression of cardiac alpha-MHC in the euthyroid state have been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495551 TI - Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit. AB - The present study was designed to investigate the effect of O2 on intracellular Ca concentration ([Ca]i) in the ductus arteriosus and the mechanisms for O2 induced ductal contraction. The force of isometric contraction of the ring of the ductus arteriosus isolated from fetal rabbits at 30 days of gestation (term, 31 days) was measured. The ductus arteriosus was loaded with fura 2, a calcium sensitive dye, and [Ca]i was determined from the ratio of fluorescence intensity at 340 and 380 nm excitation wavelengths. The ductus arteriosus was initially superfused with hypoxic control solutions and contraction was induced by application of oxygenated solutions. The O2-induced contraction of the ductus arteriosus was associated with increases in [Ca]i and was eliminated in the absence of extracellular calcium. An increase in [K]o from 5 to 50 mM, which causes membrane depolarization, induced ductal contraction. The calcium channel blockers verapamil, diltiazem, and nickel caused a similar inhibition of O2 induced contraction as well as KCl-induced contraction. The role of intracellular calcium stores in O2-induced ductal contraction was examined using ryanodine, an inhibitor of calcium uptake and release from the sarcoplasmic reticulum. The inhibition of O2-induced contraction by ryanodine was minimal. Infusion of glibenclamide, an inhibitor for opening the ATP-sensitive potassium channel, caused contraction of the ductus arteriosus in the hypoxic solution. Cromakalim, an opener of ATP-sensitive potassium channels, completely relaxed the contraction induced by O2. These data suggest that O2 increases [Ca]i and causes contraction in the ductus arteriosus. Application of O2 may change from anaerobic to aerobic metabolism and depolarize membrane potential by closing the ATP-sensitive potassium channel, which in turn increases calcium influx via the voltage dependent calcium channel. Mechanisms other than the ATP-sensitive potassium channel may also be involved in the O2-induced contraction and remain to be studied. PMID- 8495552 TI - Alterations in electrical activity and membrane currents induced by intracellular oxygen-derived free radical stress in guinea pig ventricular myocytes. AB - Oxygen-derived free radicals (O-Rs) are thought to induce alterations in cardiac electrical activity; however, the underlying membrane ionic currents affected by O-Rs and the mechanisms by which O-Rs induce their effects on ion channels in the heart are not well defined. In this study, we investigated the time-dependent changes in resting membrane potential and action potential configuration and changes in steady-state membrane currents in guinea pig ventricular myocytes after intracellular application of an O-R-generating system. O-Rs were generated from the combination of dihydroxyfumaric acid (3 mM) and FeCl3:ADP (0.05:0.5 mM) added to the pipette solution that was used to record membrane potential and currents via the whole-cell variant of the patch-clamp technique. Intracellular exposure of myocytes to the O-R-generating solution induced three stages of changes: 1) an early depolarization (5-10 mV) and an increase in action potential duration accompanied by a decrease in resting inward rectifying K+ current conductance, 2) delayed afterdepolarizations and triggered activity caused by the activation of transient inward current mediated by Na(+)-Ca2+ exchange, with failure to repolarize and sustained depolarization between -35 and -20 mV, reflecting the stimulation of nonselective cation current, and 3) a late stage of marked decline in action potential duration, hyperpolarization, and loss of excitability accompanied by activation of the outward current through ATP sensitive K+ channels. These alterations in electrical activity and membrane currents could be prevented by pretreatment with N-(2-mercaptopropionyl)glycine (500 microM), a scavenger of hydroxyl free radicals. The alterations associated with stages 1 and 2 but not stage 3 were completely abolished on intracellular Ca2+ chelation (5 mM EGTA in the pipette solution) or disruption of sarcoplasmic reticulum Ca2+ handling with ryanodine (10 microM). This study shows that intracellular O-R stress causes specific alterations in membrane ionic currents, leading to changes in resting membrane potential and action potential configuration. Moreover, the data indicate that an elevation in intracellular Ca2+ due to abnormal Ca2+ handling by the sarcoplasmic reticulum is a cause of some of the alterations in membrane currents during O-R stress. PMID- 8495553 TI - Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. AB - Angiotensin II has been reported to be a hormonal stimulus of cardiac growth, a response that may involve myocyte hypertrophy as well as growth of nonmyocytes. This study was designed to determine whether neonatal rat cardiac fibroblasts have an angiotensin II receptor that is coupled with hypertrophic and/or proliferative growth. Competitive radioligand binding studies showed that cardiac fibroblasts have a single class of high-affinity (IC50, 1.0 nM) angiotensin II binding sites (Bmax, 778 fmol/mg protein) that are sensitive to the competitive nonpeptide AT1 receptor antagonist losartan (IC50, 13 nM). Other angiotensin peptides competed for [125I]angiotensin II binding in the following rank order: angiotensin II > angiotensin III > angiotensin I > > [des-Asp1-des Arg2]angiotensin II. A nonhydrolyzable analogue of guanosine triphosphate increased the dissociation rate of bound [125I]angiotensin II and decreased hormone binding to the receptor at equilibrium. The angiotensin II receptor was coupled with increases in intracellular calcium. Incorporation of precursors into protein, DNA, and RNA in response to angiotensin II was determined. In serum deprived cultures, a 24-hour exposure to 1 microM [Sar1]angiotensin II increased rates of phenylalanine, thymidine, and uridine incorporation by 58%, 103%, and 118%, respectively. These increases were blocked by the noncompetitive AT1 receptor antagonist EXP3174. After 48 hours, [Sar1]angiotensin II increased total protein and DNA of cardiac fibroblasts by 23% and 15%, respectively, with no change in the protein/DNA ratio. [Sar1]Angiotensin II increased cell number by 138% after a 24-hour exposure, without affecting cell area. In summary, cardiac fibroblasts have G protein-linked AT1 receptors that are coupled with proliferative growth. These results suggest that angiotensin II-induced cardiac hypertrophy is, in part, secondary to stimulated increases in nonmyocyte cellular growth. PMID- 8495554 TI - Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits. AB - This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition. PMID- 8495555 TI - Role of shear stress and endothelial prostaglandins in flow- and viscosity induced dilation of arterioles in vitro. AB - We have studied the effect of changes in shear stress on diameter of isolated arterioles of rat cremaster muscle. The steady-state active diameter of arterioles at a constant perfusion pressure (60 mm Hg) was 80 +/- 1.2 microns. The vessels' passive diameter (Ca(2+)-free solution) was 156 +/- 1.8 microns. Changes in shear stress were induced either by an increase in flow (velocity) or by an increase in viscosity of the perfusion solution. At a constant perfusion pressure, the stepwise increase in perfusion flow (0-80 microliters/min in 10 microliters/min steps) elicited, with a delay of approximately 20 seconds, a gradual increase in diameter up to 46%. At a constant 20-microliters/min flow rate, increases in viscosity of the perfusate (2%, 4%, and 6% dextran [molecular weight, 77,800]) caused a gradual vasodilation up to 22%. Varying flow and viscosity of the perfusate simultaneously resulted in an upward shift of the flow diameter curve. Both flow- and viscosity-induced dilations were eliminated by the removal of the endothelium of arterioles (by air) or were inhibited by indomethacin (10(-5) M). The efficacy and specificity of these inhibitory treatments were assessed with vasoactive agents whose action, with regard to endothelial mediation, has been determined previously. The arteriolar dilation maintained calculated wall shear stress close to control values during increases in flow and/or viscosity of the perfusate, but when the dilation was inhibited by removal of the endothelium or by indomethacin, wall shear stress increased significantly in a cumulative manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495556 TI - Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters. AB - Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells. To characterize regulation of vascular IGF I receptors, we performed radioligand displacement experiments using rat aortic smooth muscle cells (RASMs). Serum deprivation for 48 hours caused a 40% decrease in IGF I receptor number. Exposure of quiescent RASMs to platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or angiotensin II (Ang II) caused a 1.5 2.0-fold increase in IGF I receptors per cell. After FGF exposure, there was a marked increase in the mitogenic response to IGF I. IGF I downregulated its receptors in the presence of platelet-poor plasma. Stimulation of protein kinase C (PKC) by exposure of quiescent RASMs to phorbol 12-myristate 13-acetate caused a biphasic response in IGF I binding; there was a 42% decrease in receptor number at 45 minutes and a 238% increase at 24 hours. To determine the role of PKC in growth factor-induced regulation of IGF I receptors, we downregulated PKC by exposing RASMs to phorbol 12,13-dibutyrate (PDBu) for 48 hours. PDGF- and FGF- but not Ang II-mediated upregulation of IGF I receptors was completely inhibited in PDBu-treated cells. Thus, acute PKC activation by phorbol esters inhibits IGF I binding, whereas chronic PKC activation increases IGF I binding. PDGF and FGF but not Ang II regulate vascular IGF I receptors through a PKC-dependent pathway. These data provide new insights into the regulation of vascular smooth muscle cell IGF I receptors in vitro and are of potential importance in characterizing vascular proliferative responses in vivo. PMID- 8495557 TI - Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. AB - The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning. PMID- 8495558 TI - Oral contraceptive treatment decreases arterial low density lipoprotein degradation in female cynomolgus monkeys. AB - The effect of oral contraceptive therapy on early events in atherogenesis was studied in female cynomolgus monkeys. After a 1-month dietary challenge, monkeys were randomized into three groups stratified by total plasma cholesterol and high density lipoprotein cholesterol concentrations. The monkeys were then fed a cholesterol-containing diet for 16 weeks. This relatively short period ensured that studies were done before any treatment-induced differences in arterial morphology occurred. Monkeys were treated with either diet alone (control group), with the addition of a monophasic oral contraceptive (equivalent to a human dose of 50 micrograms ethinyl estradiol and 500 micrograms norgestrel per day), or with a triphasic oral contraceptive (equivalent to a human dose of 30-40 micrograms ethinyl estradiol and 50-125 micrograms levonorgestrel per day). Twenty-four hours before necropsy, low density lipoproteins (LDLs) labeled with 131I and LDLs labeled with the residualizing label 125I-tyramine cellobiose were injected into the animals. The arterial LDL degradation rate, amount of undegraded LDLs, and total LDL accumulation were then determined. Although there were regional differences in LDL metabolism, both treatments decreased the rate of LDL degradation and LDL accumulation in the coronary arteries and other arterial sites. Treatment also resulted in significantly lower LDL molecular weights. Despite a trend toward a more atherogenic lipid profile (decreased high density lipoprotein cholesterol and increased total plasma/high density lipoprotein cholesterol ratio), oral contraceptive treatment may inhibit atherogenesis by decreasing arterial LDL degradation. PMID- 8495559 TI - Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current? AB - To gain insight into the molecular basis of cardiac repolarization, we have expressed K+ channels cloned from ventricular myocardium in Xenopus oocytes. A recently identified human cardiac K+ channel isoform (human Kv1.4) has properties similar to the 4-aminopyridine-sensitive calcium-insensitive component of the cardiac transient outward current. However, these channels recovered from inactivation much slower than native channels. Hybrid channels consisting of subunits from different K+ channel clones (delayed rectifier channels [Kv1.1, Kv1.2, and Kv1.5] and Kv1.4) were created by coinjection of cRNAs in oocytes. Multimeric channels consisting of Kv1.4:Kv1.1, Kv1.4:Kv1.2, and Kv1.4:Kv1.5 were expressed and compared. The hybrid channels displayed characteristics of heterotetrameric channels with kinetics that more closely resembled a native cardiac transient outward current. The inactivation and recovery from inactivation of the heteromeric channels indicated that the presence of a single inactivating subunit (Kv1.4) was probably sufficient to cause channel inactivation. The results demonstrate that expression of different K+ channel genes can produce channel protein subunits that assemble as heteromultimers with unique properties. It is shown that certain combinations of voltage-gated K+ channels probably do not contribute to native transient outward current. However, one combination of subunits could not be excluded. Therefore, this mechanism of channel assembly may underlie some of the functional diversity of potassium channels found in the cardiovascular system. PMID- 8495560 TI - Causative factors in unilateral giant papillary conjunctivitis. AB - Giant papillary conjunctivitis (GPC) is usually a bilateral disease. However, in a small number of cases, GPC can be manifested as a unilateral, or a markedly asymmetrical disease in patients wearing bilateral contact lenses. We reviewed the clinical records of 148 patients with GPC to determine the incidence of unilateral GPC and its causative factors. Specifically, charts were reviewed for data on refractive error, keratometry, lens fit, lens care, lens replacement, and the presence or absence of associated ocular abnormalities (dry eyes, blepharitis, previous injury, or surgery). Fourteen patients with unilateral or markedly asymmetrical disease were identified. Overall, no statistically significant difference was found in lens care, refractive error, or keratometric measurements in the affected and unaffected eyes. While not statistically significant, infrequent lens replacement appears to be an important factor in the development of unilateral GPC. Three patients had a history of wearing an older lens in the GPC eye. Two patients were found with unilateral meibomian gland dysfunction involving the affected eye, and one patient had undergone surgery on the affected eye. No causative factor was identified in eight cases. PMID- 8495561 TI - A new method to assess contact lens care compliance. AB - Failure to comply with contact lens care instructions is a conspicuous finding among both symptomatic and asymptomatic patients. We used a new methodology to quantify the extent of noncompliance and its clinical significance among 170 soft lens wearers. All patients were interviewed and asked to demonstrate their lens care practices. The significance of deviations from package insert instructions was assessed by 22 ophthalmologists and optometrists with regard to potential impact on safety and comfort. Virtually all patients were noncompliant with at least one required procedure. Noncompliant behavior that could significantly affect safety was more common and judged by practitioners to be of more concern than deviations that could affect comfort. Fifty-seven percent of the patients used disinfection procedures that could seriously affect safety. Overall, the study methodology was found to be very effective both for quantifying noncompliance and for evaluating its clinical significance. PMID- 8495562 TI - Morphological and biochemical evaluation for rigid gas permeable contact lens extended wear on rabbit corneal epithelium. AB - We studied the effects of 24-hour wear of rigid gas permeable (RGP) contact lenses of varying oxygen transmissibilities on the rabbit cornea by measuring concomitant lactate dehydrogenase (LDH) activity in tears and by in vivo tandem scanning confocal microscopy (TSCM). We used a PMMA lens and rigid gas permeable (RGP) lenses that had Dk/L values ranging from 7 to 64 x 10(-9) (cm/sec) (mL O2/mL mmHg) and a uniform 0.15 mm thickness. After 6- and 24-hour contact lens wear, rabbit tear LDH activity increased according to the decrease in the Dk of RGP lenses. Tear LDH activity after 24 hours of lens wear was higher than after 6 hours. The observed increase in tear LDH activity was correlated with in vivo corneal epithelial morphology by tandem scanning confocal microscopy. The observed severity of desquamation and swelling of corneal epithelial cells was dependent upon the Dk/Ltotal of contact lenses worn, which directly related to the contact lens induced corneal hypoxia. Based on the results of this study, we conclude that: 1) a nap or accidental overnight wear of contact lenses with less than 20 x 10(-9) Dk/Ltotal could cause severe corneal epithelial damage; 2) the ultra high Dk lens appeared to alter the ocular surface least; and 3) TSCM accompanied with tear LDH assay is an objective, non-invasive in vivo method to assess the effect of contact lens wear on the ocular surface over time at the cellular level. PMID- 8495563 TI - Micropachometric investigation of rigid contact lens-induced corneal dystrophies. AB - We evaluated rigid contact lens associated changes in central corneal thickness using an improved method of pachometry. After altering one lens parameter (e.g., lens diameter or base curve) and keeping all other parameters constant, we evaluated 30 rigid lens patients at 4-hour intervals over 20-hour periods. Using micropachometry we were able to detect changes as small as 10-20 microns in the central cornea region. We found that the degree of corneal swelling from rigid contact lens wear can vary from one area to another. Thinning in one area can result from lens compression, while thickening in an adjacent area can result from lens-induced hypoxia. Using micropachometry for the early detection of corneal changes such as thinning may help to avoid problems associated with long term lens wear. PMID- 8495564 TI - Excimer laser keratectomy for the correction of myopia. AB - We present the preliminary refractive and visual results in 46 sighted eyes that had undergone excimer photorefractive keratectomy. Although our sample size was small and the follow-up relatively limited (3-6 months), a few important conclusions were drawn. The visual and refractive results compare quite favorably to the preliminary results with radial keratotomy. Thirty-four of 46 patients (74%) were within 1 D of emmetropia; and 45 (98%) were within 2 D at the end of the follow-up period. Forty-four patients (96%) achieved at least 20/40 vision, with more than half achieving 20/20 or better. We encountered no significant vision threatening complications. Twenty of 46 patients (43%) complained of night vision disturbances, but symptoms improved in all patients by 6 months. The majority of patients developed trace epithelial haze; however, corneal haze did not produce reductions in visual acuity. Though the preliminary results of our study of the safety and efficacy of excimer photorefractive keratectomy are promising, further study of long-term vision stability and corneal clarity is clearly needed. PMID- 8495565 TI - Should residents study contact lenses? PMID- 8495566 TI - Complications and symptoms with disposable daily wear contact lenses and conventional soft daily wear contact lenses. AB - We conducted a historical cohort study of 1,954 myopic cosmetic contact lens wearers (1,258 disposable soft daily wear lens users and 696 conventional [nondisposable] soft daily wear lens users). Our aim was to estimate the rates of complications and symptoms among patients using daily wear disposable contact lenses on a regular disposal regimen and to compare these with rates for conventional soft daily wear users. Patients were selected from five contact lens practices in Denmark. Data were abstracted from the eye care practitioners' office records for the period October 1987 through December 1989. Virtually all of the disposable lens users were on a two-week disposal regimen. Overall, the prevalence of complications was significantly lower among the daily wear disposable lens users than among the conventional soft daily wear lens users. The incidence of corneal ulcers did not differ significantly between the two study groups. As compared to conventional soft daily wear lens users, disposable daily wear lens users reported symptoms less frequently at routine scheduled visits and had a lower rate of unscheduled visits for complications and symptoms. PMID- 8495567 TI - Intravenous cholangiography revisited. AB - The efficacy and safety of IVC with the new agent has not, in our opinion, been firmly established. In these circumstances we do not feel its routine use preoperatively in patients being considered for laparoscopic cholecystectomy is justified. We remain uncertain about its ultimate safety and are unconvinced that it is able, reliably, to demonstrate ductal anomalies which might increase the risk of iatrogenic injury. If imaging of ductal anatomy is important then it is best to obtain it intraoperatively. The radiologist often acts as an essential guide to the surgeon; as interventionist he frequently actually usurps the surgeon's role; and occasionally has to come to his rescue. In our opinion, he should not be asked to perform a procedure of unproven efficacy and uncertain safety in order to allow the surgeon willfully to abandon good surgical practice. PMID- 8495568 TI - The role of radiology in the staging of neuroblastoma. PMID- 8495569 TI - Bronchiolitis obliterans: high resolution CT findings and correlation with pulmonary function tests. AB - In order to characterize the appearances of bronchiolitis obliterans on high resolution CT (HRCT) and to relate the extent of HRCT abnormalities to pulmonary function tests, the HRCT scans of 18 patients with bronchiolitis obliterans were examined by two independent observers. The underlying causes for the development of bronchiolitis obliterans were penicillamine therapy (n = 5), previous infection (n = 4), graft-vs-host disease (n = 3), and miscellaneous causes (n = 6). Abnormal HRCT findings were present in all cases. The commonest HRCT abnormalities consisted of patchy areas of decreased parenchymal attenuation (n = 15), subsegmental (n = 12) and segmental (n = 6) bronchial dilatation and centrilobular branching structures (n = 5). There was no significant correlation between the extent of abnormalities and the static lung volumes or the impairment in gas transfer (all P values > 0.05). The only significant correlation was between the number of segments with subsegmental bronchial dilatation and the forced expiratory volume in one second (Wilcoxon r = 0.61, P < 0.01). We conclude that the great majority of patients with bronchiolitis obliterans have HRCT abnormalities. However, there is poor correlation between the extent of abnormalities on HRCT and functional impairment. PMID- 8495570 TI - The effect on apparent size of simulated pulmonary nodules of using three standard CT window settings. AB - This study was undertaken to determine whether three commonly used combinations of CT display window settings permit accurate measurement of pulmonary nodule size during thoracic CT examination. Forty-five rounded nodules of synthetic material of approximate soft tissue density (+70 Hounsfield units; HU), varying in size from 5.8 mm to 21.4 mm, were suspended in surgical gauze (-900 HU to -950 HU) to simulate pulmonary nodules. CT images were obtained for each nodule using 10 mm and 2 mm CT collimation and the size of each nodule was measured at three window settings: (a) 'soft tissue setting': window width (WW) 400 HU, window level (WL) +20 HU; (b) 'lung setting'. WW 850 HU, WL -750 HU; (c) 'broad lung setting': WW 1350 HU, WL -550 HU. Measurements obtained using either lung setting were highly accurate irrespective of collimation while measurements obtained using soft tissue settings were inaccurate. The choice of display window settings is an important consideration when CT is used to assess the size of pulmonary nodules. PMID- 8495571 TI - Tumefactive biliary sludge: a sonographic pseudotumour appearance in the common bile duct. AB - Two patients with obstructive biliary symptoms were shown to have dilated bile ducts on ultrasound. Within the lumen of both distal common ducts (CBD) large low echogenicity polypoid masses without acoustic shadowing were seen. MRI in one patient showed a polypoid filling defect in the lower CBD corresponding to the ultrasound appearance. Instrumentation at the lower end of both CBDs caused disintegration of the polypoid configuration resulting in the more typical layered appearance of biliary sludge. Sludge in the gall-bladder as seen on ultrasound is rarely known to cause a pseudotumour appearance. It has not previously been reported as occurring in the CBD and awareness of the tumefactive appearance of biliary sludge in the common duct is important and should help avoid possible misinterpretation. PMID- 8495572 TI - Dysembryoplastic neuroepithelial tumour as a potentially treatable cause of intractable epilepsy in children. AB - Dysembryoplastic neuroepithelial tumour (DNT) represents a morphologically unique and surgically treatable benign lesion typically associated with complex partial seizures (CPS). Although the radiological features are not pathognomonic the histology is quite distinct. They may account for a significant minority of children with intractable CPS. We present four histologically proven cases to demonstrate and discuss the range of radiological features. Recent recognition that CPS may be caused by a number of conditions including DNT emphasizes that all children with partial seizures should have radiological investigations early in their course. PMID- 8495573 TI - The linear echogenic hilus in cervical lymphadenopathy--a sign of benignity or malignancy? AB - The linear echogenic hilus seen within lymph nodes on ultrasound examination has been proposed as a sign of benignity. The echogenic line is thought to represent the converging sinuses within the medulla of the lymph node. Forty-six cases with a linear echogenic hilus within a cervical lymph node are presented, where a cytological or histological diagnosis was obtained. In 27 cases (58.7%) the diagnosis was malignancy, in seven cases (15.2%) tuberculosis and the remaining 12 cases (26%) were benign. In our experience the linear echogenic hilus should not be regarded as a sole criterion for benignity. A cytological diagnosis, preferably by an ultrasound-guided fine needle aspiration, should always be sought. PMID- 8495574 TI - The value of plain film findings in hydatid disease of bone. AB - The radiographic features of hydatid disease of bone have been reviewed in 16 Kuwaiti patients. The majority of the lesions were in the lower limb or pelvis, and the commonest presentation was with a pathological fracture. The radiological signs seen most often were lucent lesions in the bone, associated with expansion of the bone and thinning of the cortex. In patients with these signs soft tissue calcification appeared to be highly suggestive of hydatid disease. The disease was diagnosed before operation in only half the patients. In areas where the disease is endemic hydatid disease should be suspected when the lesions described are seen on plain films. PMID- 8495575 TI - Computed tomography of healing condylar fractures with some clinical correlations. AB - A longitudinal study using computed tomographic (CT) examinations has been performed in 79 patients with condylar fracture of the temporomandibular joint (TMJ). CT scans were performed following healing to demonstrate the new condylar shape. Maximal incisor distance was measured in all patients. Patients with mild deformities of the condyles had satisfactory function of the TMJs with a maximal distance between the incisors that was similar to 50 healthy controls (average 45 mm). Fifteen patients with severely deformed condyles and an abnormal shape of the glenoid fossa had an average maximal distance between the incisors of 16 mm which corresponded with severe malfunction of the TMJs. The remaining 42 patients with moderate condylar deformity had an average maximal distance between the incisors of 29 mm and the disability of the TMJs was considered to be moderate. The results were statistically significant. There was no resorption of the fractured condylar head or bone fragment. The correlation of the fractured head or fragment and the remodelling of the condyle during the healing process determined the final alignment of the fractured condyle to the glenoid fossa on which the TMJs' function was dependent. PMID- 8495576 TI - Titanium lines: a manifestation of metallosis and tissue response to titanium alloy megaprostheses at the knee. AB - Titanium alloy, in its Ti-318 (Ti-A16-V4) format, is a widely used material for orthopaedic implants. However, it has frequently been reported as causing black staining of the periprosthetic tissues as a result of debris from metallic wear. This process of metallosis has been implicated in implant failure. We report three cases in which titanium alloy prostheses for primary bone tumours at the knee have caused the formation of fluid-filled cysts containing metallic debris. The cysts result in radiological appearances which may mimic soft tissue tumour recurrence and also contribute to post-operative failure of the extensor mechanism of the knee. PMID- 8495577 TI - An assessment of Gd-DTPA as a CT contrast agent in the renal tract. AB - Intravenous gadolinium diethylene triamine penta-acetic acid (Gadopentetate dimeglumine, Gd-DTPA) is visualized as a radiographic contrast agent in the renal tract on computed tomography (CT). In this study the CT appearance of this contrast agent within the renal collecting systems of 12 patients is described following a Gd-DTPA enhanced magnetic resonance imaging (MRI) study. The CT appearances are variable and not predictable on the basis of time from injection, age, sex or indices of renal function. PMID- 8495578 TI - Case report: CT demonstration of extravasated contrast medium from traumatic rupture of the gastric artery. AB - We present a case where CT demonstrated intraperitoneal contrast medium subsequently shown to be due to active haemorrhage from a ruptured gastric artery. The appearances may be mistaken for traumatic bowel perforation and the differential is discussed. PMID- 8495579 TI - Case report: large bowel strictures in retroperitoneal fibrosis. AB - Large bowel strictures in retroperitoneal fibrosis (RPF) are uncommon. We report a case of multiple colonic strictures in a patient presenting with RPF and document their resolution following steroid therapy. PMID- 8495580 TI - Case report: torsion of the gall-bladder on ultrasound--differentiation from acalculous cholecystitis. AB - Acalculous cholecystitis is usually seen in critically-ill patients while torsion of the gall-bladder tends to arise de novo, pre-disposed to by an absent mesentery. There are ultrasonic features in common but the most useful distinguishing finding is the sign of the 'floating gall-bladder'. A case is reported and the ultrasound literature reviewed. PMID- 8495581 TI - Case report: MR imaging of a carcinoid tumour of the liver. AB - A surgically confirmed solitary primary liver carcinoid tumour is described. MR imaging demonstrated a low signal intensity mass on T1-weighted images, a low signal intensity mass with small area of higher intensity on fat saturation T1 weighted images, and heterogeneous high signal intensity mass on T2-weighted images. The fibrous capsule and septa were demonstrated as low signal intensity bands on both proton- and T2-weighted images. PMID- 8495582 TI - Case report: primary carcinoid tumour of the testis--ultrasound appearances. AB - Primary carcinoid tumour of the testis is extremely rare. We describe a case of testicular carcinoid, discuss the ultrasound appearances and differential diagnosis. PMID- 8495583 TI - Colour flow imaging of calf vein thrombosis. PMID- 8495584 TI - Development of a serologic panel for the recognition of nocardial infections in a murine model. AB - A murine model was used to develop a sensitive and specific serologic test for clinical and subclinical infections caused by Nocardia. The following tests were used: (a) enzyme-linked immunosorbent assays (ELISAs) with culture filtrate and cytoplasmic extract antigens from Nocardia asteroides; (b) ELISA with N. asteroides trehalose dimycolate (cord factor); (c) indirect immunofluorescent antibody assay with whole cells of N. asteroides; and (d) Western-blot analysis for the 54 to 55-kD, 36-kD, and 62-kD proteins of N. asteroides. The sera from BALB/c mice, experimentally infected with nonlethal doses of three species of Nocardia, nine species of Mycobacterium, Rhodococcus equi, two species of Actinomadura, and two species of Streptomyces were tested using this panel. The serologic tests did, indeed, identify mice infected with nocardiae and could differentiate them from mice infected with the other actinomycetes, including mycobacteria. PMID- 8495585 TI - Medical technologists using molecular epidemiology as part of the infection control team. AB - Two medical technologists were appointed as permanent members of a new epidemiology section in the diagnostic microbiology laboratory of a large Veterans Administration Medical Center in the fall of 1989. These positions accounted for 9% of the total microbiology staff and were created on a temporary basis 2 years earlier from a need to have dedicated technical expertise for use in the culture, isolation, and typing of nosocomial organisms. The technologists have evaluated outbreaks due to Clostridium difficile, methicillin-susceptible Staphylococcus aureus, and Serratia marcescens, and have begun work on a methicillin-resistant Staphylococcus aureus (MRSA)-typing scheme. Their major responsibility has been the development and application of molecular biology techniques for the typing of nosocomial isolates, including restriction enzyme analysis of genomic DNA, plasmid profiling with and without restriction enzyme analysis, ribosomal RNA probing of restricted genomic DNA, and selected DNA sequencing of target organisms. Medical supervision rests jointly between the directors of the infection control program and the microbiology laboratory. During their tenure, infections due to C. difficile have dropped from 95 cases per year to 57 cases annually, treatment of MRSA colonization with systemic agents has been curtailed, and a case control investigation involving S. marcescens was avoided. The inclusion of medical technologists in the infection control practice of large medical care facilities, particularly with the availability of molecular epidemiologic techniques and the emergence of increasing numbers of multiply-drug-resistant pathogens, will become an essential component of these programs. PMID- 8495586 TI - Fecal leukocytes in stool specimens submitted for Clostridium difficile toxin assay. AB - To determine their diagnostic utility, fecal leukocytes were sought by methylene blue stain in 502 consecutive stool specimens submitted for Clostridium difficile toxin assay. In addition, the stability of fecal leukocytes was assessed by daily examination of 23 stool specimens stored at 4 degrees C and room temperature. The sensitivity, specificity, and positive and negative predictive values of fecal leukocytes in predicting C. difficile toxin assay results were 28%, 92%, 27%, and 93%, respectively. At 4 degrees C, fecal leukocytes retained morphology for a minimum of 3 days. Leukocytes survived as long in stool specimens containing either C. difficile toxin or an enteric pathogen as they did in stool specimens with neither finding. We conclude that testing stool specimens for fecal leukocytes is not useful for predicting the presence of C. difficile toxin, because 72% of stool specimens positive for C. difficile toxin are negative for fecal leukocytes despite their stability. PMID- 8495587 TI - Evaluation of QuickVue, a rapid enzyme immunoassay test for the detection of serum antibodies to Helicobacter pylori. AB - QuickVue is an enzyme immunoassay test for qualitative detection of serum immunoglobulin-G antibodies to Helicobacter pylori. We evaluated its ability to predict infection by H. pylori in 100 adult and 49 pediatric patients referred for gastric endoscopy. A patient was defined as infected with H. pylori if either culture or histology was positive. Of the 100 adult patients, 64 had H. pylori infection and QuickVue correctly identified 59 of the 64. Of 36 H. pylori negative patients, 20 were correctly identified as negative by the test. In this sample of patients, QuickVue had a sensitivity of 92% and a specificity of 56%. In the 49 pediatric patients, QuickVue correctly identified nine of 11 infected cases and 34 of 38 noninfected patients. In this group, the sensitivity was 82% and the specificity was 89%. Overall the test had a sensitivity of 91% and a specificity of 73%. The positive predictive value was 77% and the negative predictive value was 89%. PMID- 8495588 TI - Bacteriologic investigations of unusual mycobacteria isolated from immunocompromised patients. AB - Mycobacterial isolates from blood and other extrapulmonary sites of six patients with AIDS were investigated because the isolates grew only in liquid media and failed to grow on solid culture media even on subculturing. Our investigations indicated that these mycobacteria possess common, but unusual, characteristics and probably belong to an unrecognized species recently reported as "Mycobacterium genavense." PMID- 8495589 TI - Performance of the Kallestad Pathfinder enzyme immunoassay in the diagnosis of respiratory syncytial virus infections. AB - The Kallestad Pathfinder enzyme immunoassay (EIA) for the rapid detection of respiratory syncytial virus (RSV) antigen was compared with virus culture and direct fluorescent antibody (DFA) to determine the reliability of the EIA. During two consecutive winter respiratory seasons, 270 nasopharyngeal wash specimens were tested. RSV was detected in culture by the presence of cytopathic effect and/or an indirect immunofluorescence assay. The sensitivity of the Pathfinder EIA in comparison with isolation in tube culture was 72% (73 of 101) and the specificity was 99% (167 of 169). During the second year of the evaluation period, DFA was performed on all specimens. The sensitivity of the DFA compared with isolation in tube culture was 94%. This study indicates that the Pathfinder EIA is a very specific test for diagnosis of RSV infections, but lacks sensitivity in comparison with tube culture or direct immunofluorescence. PMID- 8495590 TI - Comparative performance of peptide-, recombinant protein-, and viral lysate-based enzyme immunosorbent assays for the detection of HIV-1 antibodies. AB - The performance of peptide-, recombinant protein-, and whole virus lysate-based enzyme immunosorbent assays (EIAs) for the detection of antibodies to the human immunodeficiency virus type 1 (HIV-1) was compared on a panel of 245 routine samples, a panel of low-positive samples, four seroconversion panels, and serial dilutions of five known positive samples. Of the 245 routine samples, 83 were confirmed to be HIV-1 antibody positive by Western blot and were reactive in the three EIAs used. Agreement between the three EIA tests was also 100% for all 162 negative samples. Although there was no significant difference in the performance of the three types of assays in seroconversion panels, the whole virus and recombinant protein-based EIAs detected 15 of 15 samples in the low-positive panel whereas only 10 of 15 samples were reactive when the peptide-based EIA was used. In addition, evaluation of diluted positive samples suggested that the virus lysate-based EIA was more sensitive than the peptide- and recombinant-based EIAs. These results show that although the three types of assays performed well on routine serum panels, differences in sensitivities were demonstrated when performance panels were evaluated. The data suggest that seroconversion and low positive performance panels should be included in evaluations of new generations of EIAs for HIV-1 antibodies. PMID- 8495591 TI - Evaluation of an enzyme-linked immunosorbent assay for the detection of Giardia lamblia in stool specimens. AB - A commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of Giardia lamblia in stool specimens was evaluated on 342 specimens submitted to the Mayo Clinic Parasitology Laboratory for routine examination. The stools were either fresh or fresh/frozen at -65 degrees C (139 specimens) or were preserved in formalin (203 specimens). ELISA results were compared with those obtained by conventional microscopic examination: 143 stools were positive by both methods and 186 were negative. Sixty-six of the negative specimens contained 96 parasites belonging to 16 species other than Giardia, indicating a low rate of cross-reactivity. There were eight "false positive" ELISA results, which included specimens from one patient who had previously had a "true positive" and another patient with multiple family members infected with Giardia. Five stools that were "falsely negative" by ELISA contained only rare G. lamblia. The ELISA sensitivity was 97%, the specificity was 96%, and the positive predictive value was 95%. Results were evenly distributed between frozen and formalinized stools. The LMD/Seradyn ELISA appears to be a simple, rapid, and accurate method for the detection of G. lamblia in unprocessed stool samples. PMID- 8495592 TI - Synergy assessed by checkerboard. A critical analysis. AB - The checkerboard dilution test is widely used for evaluation of in vitro synergy for multiple drugs, although problems in performance, standardization, and interpretation have been noted. A major problem inherent in this commonly used method is the use of twofold dilutions for the antibiotic concentrations. We evaluated an alternative method proposed by Horrevorts and colleagues that preserved the twofold dilution scheme. Giant checkerboards were constructed from a series of component checkerboards using rifampin and minocycline against Staphylococcus aureus. We found that this method improved the stability of the fractional inhibitory concentration (FIC) indices, but required substantially more labor and generated other problems. FIC interpretation and calculation remained compromised by the twofold dilution scheme. We have analyzed the theoretical basis of the checkerboard and its FIC calculation and conclude that the twofold dilution with its exponential increase in dilutions makes this method of synergy evaluation inherently unstable. The principle of examining growth at multiple dilutions of combined antibiotics is valid for assessment of synergy, but newer methods need to be devised. PMID- 8495593 TI - Ultrastructural evaluation of some aspects of the endocrine activity of pituitary adenomas. PMID- 8495594 TI - Diabetes mellitus secondary to chronic pancreatitis. AB - From the present review it appears that insulin-dependent diabetes is a common finding in chronic pancreatitis, and impaired secretion of insulin from beta cells of the pancreatic islets is essential for the development of this form of secondary diabetes. Judged from a positive correlation between insulin secretory capacity and stimulated pancreatic enzyme output, beta-cell function may decrease in parallel with exocrine pancreatic function. However, in patients with insulin dependent diabetes secondary to chronic pancreatitis beta-cell function was preserved to a greater extent and glucoregulation was better than in comparable Type 1 (insulin-dependent) diabetic patients. Immunological phenomena and associations with certain HLA-alleles characterizing Type 1 diabetes mellitus were not found in insulin-dependent diabetes secondary to chronic pancreatitis. This may contribute to the slower destruction of the beta-cells in chronic pancreatitis than encountered in Type 1 diabetes. The small number of chronic pancreatitis patients who developed totally absence of endogenous insulin production still have some alpha-cell function during i.v. arginine and meal stimulation. However, insulin-induced hypoglycemia and insulin withdrawal did not stimulate glucagon secretion in the secondary diabetic patients in contrast to comparable Type 1 diabetics. Nevertheless, blood glucose counterregulation is intact in the secondary diabetics due to preserved catecholamine secretion. Furthermore, ketonemia develops during dissipation of insulin, in spite of absence of increased glucagon secretion, emphasizing the role of insulin dissipation for the development of ketoacidosis in this form of diabetes. The suggested increased susceptibility to severe hypoglycemia and less tendency to development of ketonemia may further be influenced by altered insulin sensitivity, nutritional factors and concomitant hepatic failure in diabetes secondary to chronic pancreatitis. Pancreatic polypeptide secretion was absent in chronic pancreatitis without endogenous insulin production. Pancreatic polypeptide secreting cells thus seem to be at least as vulnerable as the beta cells to the destructive processes characterizing chronic pancreatitis, whereas glucagon secreting alpha-cells preserve secretory capacity to a greater extent than PP-cells and beta-cells. No data, however, favour the view that absent pancreatic polypeptide secretion has any major effect on the glucoregulation in diabetes secondary to chronic pancreatitis. Increased plasma concentration of somatostatin was found in patients with insulin-dependent diabetes secondary to chronic pancreatitis. The source of somatostatin in the patients is unknown, but somatostatin may contribute to a reduction in overall blood glucose level in patients without endogenous insulin secretion due to inhibition of glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495595 TI - Human neutrophil structure and function with special reference to cytochrome b559 and beta 2-microglobulin. AB - Neutrophil granulocytes are the most important white blood cells in the combat of non-viral infections. Circumstantial evidence indicates that neutrophils in addition modulate the inflammatory process. Production of neutrophils takes place in the bone marrow, and mature cells egress to the circulation. Neutrophils emigrate following activation from the vessels into the tissues (chemotaxis). During this process neutrophils generate reactive oxygen species (respiratory burst) and mobilize intracellular compartments (degranulation). By degranulation, neutrophils exercise influence on nearby cells or bacteria by extracellular release of intragranular proteins (exocytosis), and intensify plasma membrane related processes, such as chemotaxis and respiratory burst, by translocation of membrane-bound proteins to the surface (upregulation). Ultimately, microorganisms may be killed intracellularly following engulfment (phagocytosis). The thesis presents results of protein-chemical analysis of human neutrophils, based on studies of intact cells and subcellular structures (subcellular fractionation). By fractionation, azurophil granules and specific granules can be disunited from each other and from plasma membrane and secretory vesicles. Only partial separation of plasma membrane and secretory vesicles can be obtained. Subcellular structures are identified by markers, e.g. vitamin B12 binding protein for specific granules, and latent alkaline phosphatase for secretory vesicles. The studies demonstrated tetranectin in neutrophils, localized exclusively in the secretory vesicles. Tetranectin was released by incubation of neutrophils in the presence of weak, inflammatory stimuli and paralleled the upregulation of alkaline phosphatase, but preceded degranulation of specific granules. Alkaline phosphatase has previously been employed as a plasma membrane marker. A novel ELISA for HLA class I antigen was introduced as a new plasma membrane marker. Results obtained by this assay showed upregulation of alkaline phosphatase occurring without a concurrent redistribution of HLA antigen. This indicates that the two proteins are localized in separate compartments. Upregulation of alkaline phosphatase induced by weak stimuli, however, paralleled the translocation of cytochrome b559, anticipated to be the terminal component in the respiratory burst, and known to be localized primarily in the specific granules. The present studies indicate that 15% of cytochrome b is localized in the secretory vesicles. An ELISA was established for quantitation of beta 2-microglobulin, the light chain of HLA class I antigens. The concentration of beta 2-microglobulin in plasma from patients with chronic myeloid leukaemia was found to correlate with the concentration of vitamin B12 binding protein.4+ Measurements in neutrophils demonstrated 65% of the total content of beta 2-microglobulin to be localized in the specific granules, and 20% to be present in secretory vesicles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495596 TI - Chronic lymphocytic leukaemia: newer prognostic approaches in relation to clinical stage. PMID- 8495597 TI - Human reabsorptive sweat duct in primary cell culture. Cellular mechanisms of ion transport and their regulation with special reference to cystic fibrosis. PMID- 8495598 TI - The hepatic catabolic stress response. Hormonal regulation of urea synthesis after surgery. AB - Following non complicated surgical trauma in man a hepatic condition has been identified that is characterized by lower than normal plasma alpha-amino nitrogen concentration and increased plasma clearance of gluconeogenic and ureagenic amino acids. Amino acids are removed from the blood by the liver, by way of a doubling of the hepatic efficacy fo urea synthesis. At any plasma amino acid concentration twice as much amino-nitrogen is excreted as urea-nitrogen, and thus lost for protein synthesis. This hepatic stress response lasts for one week postoperatively. In rats, hysterectomy elicits a similar response, but the time of the maximum increase in urea synthesis occurs earlier. Combined neuro-hormonal blockade totally prevents the response in cholecystectomized patients. In rats, it is preventable by selective blockades of glucocorticoid action and of prostaglandins synthesis. In isolated livers catecholamines, corticosterone, and glucagon together bring about 40% of the increase in urea synthesis in vivo, but only in livers "conditioned" by hysterectomy three hours earlier. Prostaglandin E2 in itself has no effect on urea synthesis, but accelerates the effect of the hormones. The regulatory system is incompletely elucidated, although several mediators are identified. A hierarchical system is suggested and discussed, and further possible regulators indicated. The role of liver for whole body nitrogen homeostasis during stress is estimated. The increase in hepatic efficacy for urea synthesis in itself accounts for about 50% of the postoperative nitrogen loss. Identification of the pathophysiological changes following surgical trauma is probably decisive for endeavours to improve postoperative morbidity and mortality. Modification of the hepatic contribution to postoperative loss of nitrogen may be necessary. PMID- 8495599 TI - Type III procollagen peptide: studies on the circulating peptide as a marker of fibrinogenesis with special reference to the liver. PMID- 8495600 TI - Circulating and mucosal concentrations of tumour necrosis factor and inhibitor(s) in chronic inflammatory bowel disease. AB - Monokines, in particular the interleukin-1 family and tumour necrosis factor alpha, have been implicated in the pathogenesis of chronic inflammatory bowel disease. We initially assessed the circulating levels of tumour necrosis factor alpha by ELISA in 20 patients with active Crohn's disease, ten patients with active ulcerative colitis, and ten healthy volunteers. Circulating levels of tumour necrosis factor alpha did not differ significantly between patients (median 80 pg/ml, range 0-2.375) and healthy volunteers (median of 0 pg/ml, range 0-780) (p = 0.16). If a limit of 40 pg/ml was applied, 21 of 30 patients had abnormal values compared to three out of ten controls (p = 0.06), and for the subgroup of patients with Crohn's disease, there was a significantly higher number of abnormal values as compared to controls (p < 0.05), whereas no such difference was found for ulcerative colitis. A parallel study of ten Crohn's disease patients suggested that this result was not explained by differences in circulating tumour necrosis factor alpha inhibitor levels of tumour necrosis factor alpha were measured in 31 patients with active chronic inflammatory bowel disease, 16 with Crohn's disease and 15 with ulcerative colitis. Very low mucosal tumour necrosis factor alpha values were detected in only three patients. Taken together, these results suggest that increased production of tumour necrosis factor does not play a major role in the pathogenesis of chronic inflammatory bowel disease. PMID- 8495601 TI - Scientific dishonesty and good scientific practice. AB - Scientific dishonesty has been the subject of much public interest in recent years. Although the problem has had a low profile in Denmark, there is no reason to believe that it is non-existent. Several preconditions known to be important prevail here as well as in other countries, such as pressure to publish and severe competition for research grants and senior academic positions. The Danish Medical Research Council (DMRC) decided to respond to this problem by preparing a report on scientific dishonesty with suggestions to the research institutions on rules for good scientific practice and procedures for investigation of suspected dishonesty. To this end, an investigatory system was suggested. The system should consist of two regional committees and one national committee. They should be headed by high court judges and experienced health sciences researchers as members. The committees will investigate cases reported to them and conclude on whether dishonesty has been established and on whether the scientific work should be retracted. Sanctions shall remain the task of the institutions. Preventive measures comprise open access to and a long storage period for scientific data. PMID- 8495602 TI - Surgical wound dressing in outpatient paediatric surgery. A randomised study. AB - A comparison of two different wound dressings was carried out in a series of 88 paediatric patients. The patients were randomised to either Steristrip plus Cutiplast, a conventional absorbent wound dressing, or to DuoDERM, an occlusive adhesive dressing. The study, set up to show which was the most convenient dressing for minor outpatient surgery, focused on the psychological aspects of operative treatment of infants and children. The results showed that the DuoDERM group had fewer bandage changes than the Steristrip & Cutiplast group, although this was not significant. Significantly less pain was experienced on removal of the wound dressing in the DuoDERM group. When dressed with DuoDERM, children could be bathed in the immediate postoperative period without complication. In conclusion, an occlusive wound dressing (DuoDERM) seems to minimize the physical and psychological trauma to the infant or child and reduce the disruption to the child's and the parents' daily routines. PMID- 8495603 TI - 5 year cumulative index. 1988-1992. Volumes 31-35. PMID- 8495604 TI - Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM. AB - OBJECTIVE: To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation, lipid metabolism, blood rheology, and platelet reactivity. RESEARCH DESIGN AND METHODS: In a double-blind, randomized, placebo-controlled study, 24 NIDDM subjects received 1800 mg of EPA-E, 900 mg of EPA-E, or a placebo (1656 mg olive oil) daily for 8 wk. RESULTS: The EPA:arachidonic acid plasma ratio increased over an 8-wk period, then declined after a 4-wk wash-out period in the fish-oil groups in a dose-dependent way. Platelet-activating factor induced platelet aggregation decreased from 75 +/- 7% at wk 0 to 35 +/- 21% at wk 8 in the 900-mg group (P = 0.016) and from 72 +/- 11 to 40 +/- 30% in the 1800-mg group (P = 0.039), but did not change in the placebo group. No effects on ADP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly, without concomitant rise in apolipoprotein B. Triglycerides, glycemic control, lipoprotein (a), blood and plasma viscosity, erythrocyte deformability, and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced. CONCLUSIONS: Purified EPA-E in doses of 900 and 1800 mg reduces Platelet-activating factor-induced platelet aggregation without negatively affecting glycemic control. Low-density-lipoprotein cholesterol was elevated in the 1800-mg group. PMID- 8495605 TI - Relationship between glycemic control and collagen-linked advanced glycosylation end products in type I diabetes. AB - OBJECTIVE: To evaluate the relationship between glycemic control over a 3-yr period and tissue levels of advanced glycosylation end products. The development of renal failure, blindness, and generalized vascular occlusion continue to be the most serious ravages of diabetes. Tissue glycosylation and AGEs are felt to play an important role in the development of these sequelae, but no data are available on the relationship between AGEs and long-term glycemic control. RESEARCH DESIGN AND METHODS: We studied 48 subjects with type I diabetes. Glycemic control was determined by mean levels of HbA1, and AGEs were determined on collagenase digests of skin collagen by fluorescence at excitation/emission readings of 335/385 and 370/440 nm. RESULTS: To evaluate the relationship between glycemic control and AGE levels, control was classified as good (< or = 8.5%), fair (> 8.5% but < or = 10%), or poor (> 10%) on the basis of mean HbA1 levels during 1- and 3-yr periods. Analysis of the mean AGE levels for each level of glycemic control over 1-3 yr showed that AGEs differed significantly across categories of glycemic control (P = 0.04 and 0.003), with the lowest AGE levels associated with good and the highest with poor glycemic control. The relationship also was highly significant when adjusted for age, sex, and duration of diabetes, and when examined by Pearson's correlation coefficients (P = 0.02 and 0.008). CONCLUSIONS: Finding a relationship between glycemic control over 1-3 yr and tissue levels of AGEs suggests that AGEs can be modified and possibly reversed by improved glucose levels. PMID- 8495606 TI - Glucose concentration in subcutaneous extracellular space. AB - OBJECTIVE: To compare the subcutaneous glucose sensor measurements with two reference methods. Previous studies provide conflicting findings about the real glucose concentrations in subcutaneous tissue. Some suggest substantially lower concentration, whereas others measure proportionally higher glucose concentrations compared with the blood compartment. Before these results can be taken seriously as an expression of the real glucose concentration in the extracellular space, the measurements must be validated by an independent method. RESEARCH DESIGN AND METHODS: We applied a microdialysis-based enzyme sensor to measure glucose concentration in subcutaneous tissue. We also developed two reference methods: subcutaneous filtrate collection and an equilibration method using ultrafiltration membranes to support the earlier findings. We provided an anatomical model to explain the results. RESULTS: The mean overall intercellular filtrate glucose concentration, sampled with the filtrate collector and taken after a 6-h stabilization time, including the values during the glucose clamp period, was 46 +/- 9%. The mean subcutaneous glucose concentration measured with the glucose sensor, calibrated in vitro, was 44 +/- 8% of the mean venous blood glucose concentration. Mean overall intercellular equilibrate glucose concentration, i.e., the mean glucose concentration in the subcutaneous extracellular space, taken after a 4-h stabilization time, was 46 +/- 15% of the mean venous blood glucose concentration. CONCLUSIONS: The close agreement between the mean values of subcutaneous glucose concentrations, obtained with three independent methods--filtration, equilibration, and dialysis (sensor)--shows the real glucose concentration in subcutaneous interstitial fluid is approximately 50% the blood glucose value in normal humans. Our results clarify some of the conflicting evidence presented in previous studies. PMID- 8495607 TI - Population-based incidence of IDDM in the state of Sao Paulo, Brazil. AB - OBJECTIVE: To study the incidence of IDDM among children, infants to 14 yr of age, in the state of Sao Paulo, Brazil, 1987-1991. RESEARCH DESIGN AND METHODS: A prospective population-based register was established, using physician reports of newly diagnosed IDDM patients < 15 yr of age as the primary source of case identification and school surveys as the main secondary source. Data were collected according to the methods recommended by the Diabetes Epidemiology Research International group. RESULTS: Case ascertainment was estimated at 95.0, 92.8, and 98.8% complete for each of the three cities studied. The average annual IDDM incidence was 7.6/100,000 inhabitants (95% confidence interval, 5.6-9.7). We found a higher incidence rate in girls than boys. CONCLUSIONS: The incidence of childhood IDDM in a tropical region in South America (Sao Paulo, Brazil) is in the middle incidence range observed in developed countries throughout the world. Increased incidence of IDDM in girls compared with boys will be tested by the ongoing Brazilian incidence study being developed in 18 other centers across the country. PMID- 8495608 TI - Impact of resident participation in a multidisciplinary diabetes team. AB - OBJECTIVE: To determine the impact of participation in a multidisciplinary diabetes team on pediatric residents' perceptions of team members' roles. RESEARCH DESIGN AND METHODS: Pediatric residents were assigned to a traditional diabetes clinical rotation (n = 34) or to an ambulatory multidisciplinary diabetes team within their continuity clinic (n = 21). The residents and a small sample of practicing pediatricians (n = 46) completed a Likert-type instrument at the completion of the 18-mo study. RESULTS: Multidisciplinary diabetes team residents were significantly more positive about the roles for endocrinological evaluation in monitoring compliance, for the nurse educator/certified diabetes educator in assisting with sick-day management and school behavioral problems, and for the dietician in helping with cholesterol problems. They were significantly more like practicing pediatricians in their perceptions of pediatric roles in teaching sick-day management, implementing weight reduction, assisting with conflict resolution about diabetes, screening for microvascular complications, and developing behavioral strategies for metabolic control than residents in the traditional rotation. The groups did not differ in their beliefs about patient empowerment. CONCLUSIONS: Multidisciplinary diabetes team participation may be useful in modifying specific role perceptions of pediatric residents about diabetes care. It does not appear to alter perceptions favoring greater patient empowerment. PMID- 8495609 TI - Sex differences in the impact of coexistent diabetes on survival in patients with coronary heart disease. AB - OBJECTIVE: To evaluate the sex difference in the impact of diabetes on survival in patients with coronary heart disease. RESEARCH DESIGN AND METHODS: Cohort study based on a sample from a hospital registry in Chicago, IL. A total of 974 consecutive patients (585 men and 389 women) with angiographically confirmed coronary artery disease were followed for 4.6 yr. RESULTS: At baseline, 160 men and 155 women had diabetes. The age-adjusted relative risk of death from all causes for patients with diabetes versus patients without diabetes was 0.93 (95% confidence interval 0.65-1.34) in men and 1.99 (95% CI 1.30-3.05) in women. For cardiac death, the corresponding relative risk was 1.00 (95% CI 0.64-1.56) and 1.96 (95% CI 1.19-3.24) in men and women, respectively. Baseline differences in age, hypertension, body mass index, number of diseased vessels, and ejection fraction did not fully explain the excess mortality risk in diabetic women. Excess risk was apparent in both cardiac and noncardiovascular categories. Among nondiabetic patients, the risk of death was significantly lower in women compared with men (multivariate-adjusted relative risk = 0.61, 95% CI 0.41-0.89). However, the mortality risk of diabetic women became similar to men as a whole (relative risk = 1.13, 95% CI 0.80-1.60). CONCLUSIONS: Diabetes confers a substantially higher risk of mortality in women than in men when it occurs in the presence of coronary heart disease. PMID- 8495610 TI - Provider-patient communication and metabolic control. AB - OBJECTIVE: To determine whether nurses' and NIDDM patients' communication styles during consultations are related to subsequent metabolic control and to examine factors influencing patterns of communication in these consultations. RESEARCH DESIGN AND METHODS: A total of 47 NIDDM patients participated in the study and completed the following procedures: 1) assessment of baseline HbA1, 2) attended 3.5 days of diabetes education, 3) returned in 1 mo for a follow-up consultation with a nurse, and (4) returned in 9-12 wk for a follow-up HbA1 assessment. The communication variables coded from the consultations were the frequency with which nurses produced controlling, informative, and patient-centered utterances and the frequency with which patients sought information, engaged in decision making, and expressed negative affect. RESULTS: The results were as follows: 1) patients experienced poorer metabolic control after interacting with nurses who were more controlling and directive in their communication with patients (r = 0.39, P < 0.01); 2) the nurses' use of patient-centered responses was directly related to the degree to which patients expressed feelings (r = 0.34, P < 0.01) and exhibited decision-making behavior (r = 0.62, P < 0.01); and 3) several of the nurses' and patients' communicative behaviors were related to patient characteristics such as age, sex, education, and baseline HbA1 levels. CONCLUSIONS: The results suggest that providers' attempts to exert considerable control during consultations with NIDDM patients may be counterproductive and contribute to poorer outcomes. The findings also indicate that patient-centered behaviors (e.g., encouraging the patient's involvement, respecting the patient's opinion, and offering support) facilitate the patient's ability to be an active participant in the consultation. PMID- 8495611 TI - Plasma norepinephrine in sensory diabetic polyneuropathy. AB - OBJECTIVE: To examine whether changes in circulating norepinephrine are associated with the sensory disturbances of diabetic polyneuropathy. Experimental studies have indicated that NE can excite sprouts from injured nerves, producing pain. RESEARCH DESIGN AND METHODS: We measured supine and erect plasma NE in 13 normal, nondiabetic control subjects and three groups of diabetic patients: 20 without clinical neuropathy, 20 with chronic painful neuropathy, and 15 with painless neuropathy and foot ulceration. Neuropathy was characterized by symptom and deficit scores, sensory thresholds, electrophysiology, and cardiovascular autonomic function tests. Neuropathic pain was scored by the patients on a linear analogue scale. RESULTS: In painless neuropathy, NE levels were greatly reduced (supine, 1.3 nM; erect, 2.2 nM) compared with control subjects (supine, 2.4 nM; erect, 4.0 nM; P < 0.001) and were combined with grossly abnormal autonomic reflexes. NE also was reduced in the diabetic group without neuropathy (supine, 1.7 nM; erect, 2.7 nM; P < 0.01 vs. control subjects). By contrast, in painful neuropathy NE levels (supine, 2.2 nM; erect, 3.6 nM) were similar to control subjects and significantly higher than in painless neuropathy (P < 0.01). Furthermore, NE correlated with the severity of neuropathic pain (r = 0.46, P = 0.02). To assess whether pain, acting as a stressor, could account for the observed differences in NE, we also measured the stress hormones epinephrine and cortisol. They did not differ among the diabetic groups. CONCLUSIONS: Circulating NE is higher in painful than painless diabetic neuropathy. We suggest that painful neuropathy is associated with a relatively higher number of functioning sympathetic fibers that may contribute to pain. PMID- 8495612 TI - Effects of age and body fat on insulin resistance in healthy men. AB - OBJECTIVE: Aging is known to be associated with increasing insulin resistance and declining glucose tolerance. The cause for the insulin resistance, however, remains uncertain. In this study, we examined the hypothesis that at least part of the insulin resistance may be attributable to age-related changes in body composition and muscle blood flow rather than age itself. RESEARCH DESIGN AND METHODS: We studied 6 healthy, elderly (66.2 +/- 1.7 yr) and 6 younger, healthy men (31.8 +/- 3.0 yr) matched for height and weight by determination of their body composition (by underwater weighing), leg blood flow (by mercury strain gauge plethysmography), rates of glucose uptake (by stable isotope dilution analysis with 6.6 D2-glucose), and carbohydrate oxidation (by indirect calorimetry) during euglycemic hyperinsulinemic clamping. RESULTS: Body fat (kg fat mass or in percentage of body weight), rates of insulin-stimulated leg blood flow, glucose uptake, oxidation, and storage were all similar in elderly and younger men. Body fat (in percentage of body weight) of both elderly and younger men correlated closely and negatively with glucose uptake (r = -0.73, P < 0.01), glucose oxidation (r = -0.67, P < 0.05), and with glucose storage (r = -0.65, P < 0.05). In contrast, age did not correlate significantly with any parameter of glucose metabolism. CONCLUSIONS: Our data suggested that insulin sensitivity in men until around 60-70 yr of age appears to be determined more by body fat than by age. PMID- 8495613 TI - Cardiovascular reflex abnormalities in children and adolescents with diabetes mellitus. AB - OBJECTIVE: To assess the usefulness of specific cardiovascular reflex tests in childhood and to estimate the prevalence of cardiovascular reflex abnormalities among children with IDDM. In adults, abnormal cardiovascular reflexes are a frequent complication of diabetes, associated with increased morbidity and mortality. RESEARCH DESIGN AND METHODS: We measured heart-rate responses to deep breathing and standing in ambulatory children with and without IDDM between 6-19 yr of age. A subgroup of the IDDM patients was retested after 1 yr. RESULTS: We found the best techniques for detecting cardiovascular reflex abnormality in children were as follows: to record heart-rate responses to deep breathing either as the change in heart rate corrected for inspiratory heart rate or as the ratio of R-R intervals during expiration and inspiration; and to use the Maximum minimum ratio for heart-rate responses to standing. HR-DBc was lower in diabetic than nondiabetic children (28.6 +/- 9.2% [n = 248] vs. 33.6 +/- 6.8% [n = 60]; P < 0.0005). Similarly, E:I was lower in children with IDDM than control subjects (1.42 +/- 0.19 [n = 248] vs. 1.52 +/- 0.15 [n = 60]; P < 0.0005). In the IDDM group, 21% of the children had abnormal HR-DBc or E:I responses. HR-STND M/m was lower in children with IDDM than control subjects (1.28 +/- 0.20 [n = 167] vs. 1.38 +/- 0.22 [n = 45]; P < 0.014). Among children with IDDM, 11.4% had abnormal HR-STND M/m responses. Overall, 29% of IDDM children tested abnormal in either HR DBc or HR-STND M/m; 3% were abnormal in both tests. We found no correlation of HbA1c levels (n = 74) or duration of diabetes with either HR-DB, expiration to inspiration (n = 248), or HR-STND M/m (n = 167). In patients who were reevaluated after 1 yr we found a high correlation of the first and repeat HR-DBc tests (r = 0.47, n = 75, P < 0.0001), E:I (r = 0.53, n = 75, P < 0.0001), and HR-STND M/m (r = .49, n = 37, P < 0.002), but no evidence of an increased number of children with cardiovascular reflex abnormality. CONCLUSIONS: With easily performed HR-DB and HR-STND tests, we detected cardiovascular reflex abnormality in 29% of children with IDDM. We found no correlation of changes in HR-DB and HR-STND with HbA1c or duration of diabetes. These tests provide an objective clinical measurement to monitor autonomic neuropathy in children with diabetes. PMID- 8495614 TI - Lipoprotein(a) in diabetic patients and normoglycemic relatives in familial NIDDM. AB - OBJECTIVE: To compare lipoprotein(a) levels in diabetic patients and normoglycemic relatives in familial NIDDM and to assess whether Lp(a) is a risk factor for myocardial infarction in this population. RESEARCH DESIGN AND METHODS: We compared 577 patients and 261 normoglycemic relatives from 189 NIDDM multiplex families with 49 unrelated healthy individuals. Of the 577, 23 patients with previously documented myocardial infarction were further analyzed as a separate group. RESULTS: Lp(a) concentrations in diabetic patients, normoglycemic relatives, and the control group were not significantly different. Variance of Lp(a) in a given individual could not be accounted for by any clinical or biological parameter, but was strongly related to the mean Lp(a) value in his or her family. Diabetic patients with previous myocardial infarction (and their relatives) had significantly higher levels of Lp(a) than patients without coronary heart disease complaints. CONCLUSIONS: Lp(a) concentration in familial NIDDM was not related to the degree of glucose intolerance, but presented a strong familial aggregation. High Lp(a) levels seem to be an independent risk factor for myocardial infarction in this NIDDM cohort. PMID- 8495615 TI - Racial differences in the relationship between blood pressure and risk of retinopathy among individuals with NIDDM. AB - OBJECTIVE: To assess whether the prevalence of retinopathy differs between blacks and whites with diabetes and to examine differences between blacks and whites in the relationship between risk factors for and prevalence of retinopathy. Population data suggest diabetic retinopathy is either more prevalent or more severe in blacks than in whites. RESEARCH DESIGN AND METHODS: We analyzed data from a screening study for retinopathy among patients with diabetes, conducted in Maryland from 1986-1990. RESULTS: After adjusting for age, duration of diabetes, type of treatment for diabetes, and presence or absence of high blood pressure, black men with NIDDM were approximately 23% more likely to have retinopathy than other race-sex groups (not statistically significant). We also found a different relationship between systolic blood pressure and retinopathy prevalence in blacks than in whites among individuals with NIDDM. Among blacks, the risk increased as systolic blood pressure increased, even within the normal range, and reached statistical significance at > 150 mmHg. Among whites, the risk was increased only among those with high systolic blood pressure (> 140 mmHg) and did not reach statistical significance. CONCLUSIONS: Our data are consistent with the hypothesis that differences exist between blacks and whites in risk of diabetic retinopathy, and that the effect of blood pressure on risk of retinopathy differs between blacks and whites. PMID- 8495616 TI - Lipoprotein(a) concentration shows little relationship to IDDM complications in the Pittsburgh Epidemiology of Diabetes Complications Study cohort. AB - OBJECTIVE: To examine the potential associations of lipoprotein(a) and the complications of IDDM and their risk factors. RESEARCH DESIGN AND METHODS: This report focuses on 186 individuals with IDDM (mean age = 34 yr) participating in a 10-yr prospective study examining various complications. Lp(a) concentrations were evaluated for those with and without complications. RESULTS: A weak correlation was seen between Lp(a) and HbA1 (r = 0.16, P < 0.05). Lp(a) concentrations were not significantly different for those with or without proliferative retinopathy, overt nephropathy, peripheral vascular disease, or definite myocardial infarction or angina. However, an inverse association (P < 0.05) was seen with distal symmetric polyneuropathy. These results were also confirmed by categorical analyses (i.e., Lp(a) levels < or = 30 vs. > 30 mg/dl). CONCLUSIONS: These results suggest that any association of Lp(a) concentration with IDDM complications is likely to be weak or nonexistent. However, prospective studies are needed before its full role can be determined. PMID- 8495617 TI - Survey of physician practice behaviors related to diabetes mellitus in the U.S. I. Design and methods. AB - OBJECTIVE: To conduct a survey among a representative sample of primary care physicians in the U.S. to assess practice behaviors, treatment goals, and beliefs related to management of diabetes mellitus and prevention of its complications. RESEARCH DESIGN AND METHODS: A mail survey with telephone follow-up was conducted among 3481 primary care physicians in active practice in the continental U.S. A stratified probability sample was selected using the files of the American Medical Association and American Osteopathic Association. Four specialties were selected to be included in the study: family physician, general practitioner, internist, and pediatrician. Two versions of a questionnaire were constructed: one for pediatricians containing questions about IDDM only and one for the other three specialties containing questions about both IDDM and NIDDM. Physicians who were not actively engaged in practice or did not see patients with diabetes were excluded. RESULTS: Completed questionnaires were received from 1502 of 3481 sampled physicians. Based on various assumptions of eligibility among nonresponders, an overall response rate to the survey was estimated to be between 65.7 and 86.5%. Discrepancies between specialty identifications as noted on the American Medical Association/American Osteopathic Association files and as self designated were noted. CONCLUSIONS: This report describes the methodology used in the design and conduct of the survey, and data are provided to document the technical success of survey execution. This report provides the methodological basis for a series of separate reports on demographic characteristics of the physicians, their practices and their patients, and on specific attitudes, beliefs, and practice behaviors of primary care physicians in the U.S. with regard to diabetes mellitus. PMID- 8495618 TI - Attitudes and behaviors of primary care physicians regarding tight control of blood glucose in IDDM patients. AB - OBJECTIVE--To evaluate attitudes and practices of primary-care physicians toward tight blood glucose control in IDDM. RESEARCH DESIGN AND METHODS--A mail and telephone questionnaire survey was conducted on a systematic, stratified sample of 1429 family-practice physicians, general practitioners, internists, and pediatricians in active practice in the United States who treated patients with IDDM. Physicians were asked about methods they used for clinical and laboratory assessment of blood glucose control and about their attitudes and beliefs in treating IDDM. They were asked also what they consider to be acceptable ranges for blood glucose and HbA1 in IDDM patients. A score was developed reflecting three criteria for tight blood glucose control: fasting glucose 70-120 mg/dl (3.9 6.7 mM), 2-h postprandial glucose < 180 mg/dl (< 10 mM), and HbA1 < or = 8% (the nondiabetic value was specified as 5-7%). Physicians were accorded one point when their acceptable range agreed with an intensive treatment criterion (range for score 0-3). RESULTS--Only 31% of physicians agreed with all three criteria for tight control of blood glucose; 37% agreed with none or only one of the standards. Pediatricians were particularly low in their agreement with the HbA1 standard. Physicians who agreed with one of the three criteria often did not agree with the other two. With increasing value for the score, there was a greater proportion of physicians whose management practices (e.g., frequent measurement of HbA1, multiple insulin injections, patient SMBG, use of dietitian/educator in care of patients) are conducive toward tight control of blood glucose. However, even among physicians with a score of 3, HbA1 was ordered infrequently, three or more insulin injections/day was prescribed rarely, patient SMBG was less than fully endorsed, and both a dietitian and diabetes educator were used by a minority of physicians. CONCLUSIONS--It appears that primary-care physicians are not fully aware of recommended criteria for intensive treatment of blood glucose in IDDM patients or of the importance of multiple insulin injections, use of HbA1, and patient SMBG. Physician practice behaviors are less than optimal for intensive management of IDDM patients, even among physicians who agree with all three standards for intensive treatment of blood glucose in IDDM. PMID- 8495619 TI - Autonomic neuropathy predicts deterioration in glomerular filtration rate in patients with IDDM. AB - OBJECTIVE: To evaluate whether autonomic neuropathy predicts deterioration in glomerular filtration rate in IDDM patients. RESEARCH DESIGN AND METHODS: A prospective study in which 35 IDDM patients have been followed for 10-11 yr. Autonomic nerve function tests included heart-rate reactions to deep breathing (expiration-to-inspiration ratio) and to tilt (acceleration and brake indexes). GFR was evaluated by the 51Cr-EDTA plasma clearance method. RESULTS: At entry to the study, no significant differences were noted in age (39 +/- 2 [mean +/- SE] vs. 42 +/- 4 yr), duration of diabetes (20 +/- 3 vs. 23 +/- 4 yr), supine blood pressures (120/79 +/- 3/2 mmHg vs. 121/78 +/- 6/3 mmHg), and GFR (113 +/- 6 vs. 107 +/- 3 ml.min-1.1.73 m-2) between 20 patients with and 15 without autonomic neuropathy (age-corrected criteria). After 10-11 yr, GFR had decreased significantly (22 +/- 4 ml.min-1.1.73 m-2, P < 0.001) in patients with autonomic neuropathy but not (8 +/- 5 ml.min-1.1.73 m-2, NS) in patients without. In keeping with this, GFR decreased more than expected (difference in GFR/expected decrease in GFR) in patients with autonomic neuropathy, compared with those without (4.46 +/- 0.98 vs. 0.48 +/- 0.73, P < 0.005). CONCLUSIONS: Autonomic neuropathy predicts future deterioration in GFR in IDDM patients. PMID- 8495620 TI - Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. AB - OBJECTIVE: To explore the possible link between diabetic nephropathy and the enhanced activity of the polyol pathway, known to occur in IDDM subjects. RESEARCH DESIGN AND METHODS: We studied the effects of the aldose reductase inhibitor tolrestat (200 mg/day) on urinary albumin excretion rate and glomerular filtration rate in 20 IDDM patients with diabetic nephropathy. RESULTS: Six months of placebo treatment produced no significant changes in glomerular filtration rate, urinary albumin excretion rate, and renal plasma flow. Consequently, filtration fraction remained unchanged. During tolrestat treatment, glomerular filtration rate decreased from the basal value of 156 +/- 14 ml.min 1.1.73 m2 to 142 +/- 13.7 ml.min-1.1.73 m2 (P < 0.001) at 2 mo; 128 +/- 12.4 ml.min-1.1.73 m2 (P < 0.001) at 4 mo; and 123.7 +/- 13.0 ml.min-1.1.73 m2 at 6 mo. A significant decrease of urinary albumin excretion rate was observed during the trial (basal values 219 +/- 32.5 vs. 196.9 +/- 28.5 micrograms/min at 2 mo [P < 0.05]; 171.6 +/- 25.5 micrograms/min at 4 mo [P < 0.001]; and 58.6 +/- 19.3 micrograms/min at 6 mo [P < 0.001]). No significant change in renal plasma flow was seen during tolrestat treatment. Filtration fraction significantly decreased in the tolrestat group from the basal value of 0.23 +/- 0.02 to 0.21 +/- 0.01 at 2 mo (P < 0.005); 0.18 +/- 0.02 at 4 mo (P < 0.001); and 0.17 +/- 0.02 at 6 mo (P < 0.001). CONCLUSIONS: The polyol pathway is implicated in hemodynamic changes associated with early diabetic nephropathy, and aldose reductase treatment can positively influence these parameters. PMID- 8495621 TI - Lack of regional variation in IDDM risk in Japan. Japan IDDM Epidemiology Study Group. AB - OBJECTIVE: To examine the intracountry variation of IDDM incidence in Japan and compare it with data from the British Isles and the U.S. RESEARCH DESIGN AND METHODS: IDDM incidence was determined with a standardized registry approach in five geographically different areas in Japan (Hokkaido, Tokyo, Yokohama, Osaka, and Kagoshima) with a total at-risk population < 15 yr of age of 4.4 million. Data collection was completed under the guidelines of the World Health Organization DiaMond project. RESULTS: The incidence and patterns of disease were remarkably similar across the five environmentally different areas. Incidence rates per 100,000 were very low and almost identical from northern to southern Japan (Hokkaido, 2.07; Tokyo, 1.65; Yokohama, 1.66; Osaka, 1.78; and Kagoshima, 1.93). This remarkably low intra-country variation of 0.4/100,000 stands in sharp contrast with the 13.0/100,000 regional variation in the British Isles and the 10.6/100,000 variation in the U.S. CONCLUSIONS: The results suggest that the remarkable genetic homogeneity in Japan may produce uniformity of incidence. PMID- 8495622 TI - Factors involved in catheter obstruction during long-term peritoneal insulin infusion. AB - OBJECTIVE: To analyze the efficacy of ECPII and the factors responsible for technical problems often encountered. This treatment has been in use with IDDM patients since 1980. RESEARCH DESIGN AND METHODS: Forty-four IDDM patients were treated by ECPII for 42-78 mo (mean, 53 mo). RESULTS: Glycemic equilibrium was improved during treatment (mean plasma glucose level, 7.6 mM; mean GHb level, 8%). Catheter blockage was the main reason for ECPII failure (74%). Mean catheter survival of each catheter, determined by actuarial analysis, was 11.7 mo and significantly decreased with subsequent implantation. SEM of the catheter tips showed deposits composed of fibrin and cells occluding the inner lumen. Factors such as age, sex, local infection, and low insulin basal rate were not found to have any incidence on the catheter survival. Placement of the catheter in the upper part of the peritoneum, however, increased catheter survival. Anti-insulin antibodies did not seem to be directly involved in blockage. CONCLUSIONS: We conclude from this long-term experience that during ECPII, catheter blockage remains the major recurring complication, probably involving a local immune inflammatory response in the peritoneum. PMID- 8495623 TI - Effect of war on glycemic control in type II diabetic patients. AB - OBJECTIVE: To determine the effect of war-related, protracted stress on glycemic control in type II diabetic patients. RESEARCH DESIGN AND METHODS: We examined 35 patients with type II diabetes as part of their routine control in October 1990. We reexamined them in October 1991, 3 mo after the war in Croatia began. We also administered a questionnaire to assess the patients' exposure to stress and changes in diet and exercise. RESULTS: The patients were exposed to considerable stressors. The wartime diet differed from the prewar diet. We found significant changes in total serum cholesterol and TG values (P < 0.01), but we observed no significant changes in body weight, FBG, postprandial blood glucose, and HbA1c values. Insulin and glibenclamide dosages did not change. CONCLUSIONS: We detected no significant impact of stress on glycemic control, probably because of differences in individual stress responsiveness. Changes in the lipid status probably were attributable to changes in dietary habits caused by specific circumstances. PMID- 8495624 TI - Serum lipoprotein(a) in patients with diabetes mellitus. AB - OBJECTIVE: To investigate subjects with different types of diabetes mellitus regarding their serum levels of lipoprotein(a). High serum Lp(a) concentration is associated with a high risk of coronary heart disease. Diabetic patients are prone to developing coronary heart disease. RESEARCH DESIGN AND METHODS: The subjects were 66 type I diabetic patients, 100 type II diabetic patients treated with diet alone or diet combined with oral hypoglycemic agents, and 46 insulin requiring type II diabetic patients. Subjects were compared with 142 nondiabetic outpatients. RESULTS: Subjects with insulin-requiring type II diabetes mellitus were found to have an increase both in serum Lp(a) concentration and in prevalence of serum Lp(a) concentration > 30 mg/dl compared with the other groups of diabetic patients and nondiabetic control subjects. A nonsignificant increase in the prevalence of coronary heart disease was also found in insulin-requiring type II diabetic patients. The levels of serum concentrations of Lp(a) were not significantly related to the degree of glycemic control, duration of diabetes, presence of macrovascular disease, or intake of female hormone therapy. High levels of Lp(a) in this group of diabetic patients could not be explained by the presence of albuminuria. CONCLUSIONS: Insulin-requiring type II diabetic patients have high levels of Lp(a). Chronic hyperinsulinemia might be an eventual causal factor. PMID- 8495625 TI - Social and economic impact on youth-onset diabetes in Japan. AB - OBJECTIVE: To investigate the social and economic backgrounds of youth-onset insulin-treated diabetes mellitus in Japan. RESEARCH DESIGN AND METHODS: We conducted a case-control study on 35 diabetic patients with age at onset of 19.5 +/- 5.1 yr and duration of diabetes 14.9 +/- 6.7 yr. Sex- and age-matched (within 5 yr) siblings were selected as control subjects. Thirty-five matched pairs were asked to complete a questionnaire, including employment status and educational achievement. RESULTS: Overall, diabetic patients were more likely to encounter job refusal in their lives than sibling control subjects (20 vs. 0%), and most patients (6/7) who had an experience of job refusal told job interviewers about their diabetes. Although the full-time employment rate and unemployment rate did not differ significantly between patients and control subjects, income levels were lower among patients than in the sibling (1600 vs. 2500 thousand yen). A multivariate analysis indicated that patients had lower incomes than control subjects after adjusting for the effect of physical disability. Educational achievements in the patients were similar to those in the siblings. CONCLUSIONS: These results suggested that diabetic patients had several social and economic problems in Japan. Further studies in more subjects are required to grasp the social and economic impact on diabetes precisely, and minimize the social handicaps on diabetic patients. PMID- 8495626 TI - Detection and management of lipid disorders in diabetes. American Diabetes Association. PMID- 8495627 TI - Lipoprotein(a) and diabetes. An update. AB - On the basis of the available data (much of which is contradictory), I suggest that the following might summarize the role of Lp(a) in diabetes currently. 1. Lp(a) in IDDM: Concentrations are probably elevated. Concentrations are probably related to metabolic control. Concentrations are increased with microalbuminuria. 2. Lp(a) in NIDDM: Concentrations are not elevated. Concentrations do not change with metabolic control. Too few data exist to make an assessment of relation of Lp(a) to microalbuminuria in NIDDM. 3. Lp(a) and CHD in diabetes: Little current evidence shows that Lp(a) is a risk factor for CHD in diabetes. More studies- especially prospective studies with larger numbers of subjects--need to be done. PMID- 8495628 TI - How many people in the U.S. have IDDM? PMID- 8495629 TI - Nutrition management of diabetes must be individualized. PMID- 8495630 TI - Cost-effectiveness of alternative methods for diabetic retinopathy screening. PMID- 8495631 TI - Prevalence of diabetes in Asian Indians. PMID- 8495632 TI - Lipoprotein(a) levels in Japanese children with IDDM. PMID- 8495633 TI - Depression in adults with diabetes. PMID- 8495634 TI - Autonomic neuropathy in newly diagnosed diabetes mellitus. PMID- 8495635 TI - Marked decrease in serum HDL cholesterol levels by combined probucol-pravastatin treatment in hypercholesterolemic NIDDM patients. PMID- 8495636 TI - Give diabetes more national TV news coverage. PMID- 8495637 TI - Respiratory function in IDDM patients. PMID- 8495638 TI - More concerns regarding methodology in hypoglycemia study. PMID- 8495639 TI - Questionable accuracy of a filter paper method for measuring GHb. PMID- 8495640 TI - Kahn honored as winner of Banting Medal. PMID- 8495641 TI - Brownlee recipient of Outstanding Scientific Achievement Award. PMID- 8495642 TI - [The progression of kidney failure]. PMID- 8495643 TI - [Pregnancy after kidney transplantation]. AB - The course of 13 pregnancies in 12 women (mean age 28 [19-34] years) after renal transplantation was analysed retrospectively. The average period from renal transplantation to the beginning of pregnancy was 45 [7-144] months. All patients received methylprednisolone for immunosuppression, while seven each additionally received azathioprine and/or cyclosporin. At the onset of pregnancy the transplant function was good or only slightly impaired in 11 women (serum creatinine 1.3 [0.8-1.8] mg/dl). But in one patient, a diabetic with nephrotic syndrome, serum creatinine concentration was raised to 2.4 mg/dl. In six patients the cyclosporin dosage had to be increased during the pregnancy. Severe complications were: acute rejection in the 16th week of pregnancy; acute renal failure during a recurrence of haemolytic-uraemic syndrome in the 36th week; and severe renal anaemia (haemoglobin 6.7 g/dl). An irreversible rise in creatinine concentration occurred in five women and hypertension got worse in eight. The mean duration of pregnancy was 35.5 (32-38) weeks. The average birth weight was low (1892 g [970-2560 g]): five children were dystrophic. The dystrophy rate was the same under cyclosporin as under the conventional immunosuppressants. The findings indicate that pregnancy after renal transplantation presents a high risk for mother and child. It demands intensive joint care by obstetrician, paediatrician and nephrologist. PMID- 8495644 TI - [Color-coded Doppler sonography in iatrogenic spurious aneurysms in the groin]. AB - Pseudoaneurysm of the femoral artery occurred in five patients (aged between 61 and 82 years) after catheterization of the artery, four times after percutaneous transluminal angioplasty of the leg arteries and once after left-heart catheterization. The pseudoaneurysms were correctly diagnosed by colour-coded duplex Doppler sonography by demonstrating turbulence within the aneurysm and a connection to the femoral artery with bidirectional shunting. Enough pressure was exerted with the instrument head to stop flow in the aneurysm and its connection to the artery without, however, significantly reducing arterial flow. After 30-35 min flow into the aneurysm had ceased even when the compression was released. Re examination up to 11 months later (mean of 7.6 months) indicated that the treatment had been successful in all. PMID- 8495645 TI - [Mutation in the cystic fibrosis transmembrane-regulator gene in bilateral congenital ductus deferens aplasia]. AB - A 28-year-old man and his 27-year-old wife were investigated for infertility of 3 1/2 years' duration. There was azoospermia caused by bilateral aplasia of the vas deferens, and therefore it was planned to aspirate spermatozoa from the epididymis for the purpose of in-vitro fertilisation. As part of the diagnostic workup the man was investigated for those mutations of the cystic fibrosis transmembrane regulator (CFTR) gene which occur with undue frequency in association with aplasia of the vas deferens. Deoxyribonucleic acid (DNA) analysis revealed a typical three base deletion (delta F 508). In the wife, CFTR gene mutations were excluded with 80% probability. The likelihood of cystic fibrosis in this couple's children was accordingly estimated to be about 0.2%--an acceptable risk. Assisted fertilization in patients with bilateral aplasia of the vas deferens should not be undertaken until they have been thoroughly investigated and informed of the risks. PMID- 8495646 TI - [Cardiac myxomas]. PMID- 8495647 TI - [The costs of photocopies of patient documents]. PMID- 8495648 TI - [A stay at high altitude in infancy]. PMID- 8495649 TI - [Skin tumors and genetic damages from arsenicals]. PMID- 8495650 TI - [Omeprazole in H2-receptor blockader-refractory sclerosing ulcers of the esophagus]. PMID- 8495651 TI - [The incidence of asthma and allergic diseases in children in the united Germany]. PMID- 8495652 TI - Adaptive mechanisms of saccadic system in diagnostic use. AB - The possibilities of diagnostic use of saccades are given in pathological eye movements as well as in adaptive mechanisms. They are used to offset the degradation of oculomotor performance resulting from interference along the chain of neural conducting, in neuromuscular transmission and in muscle function. Pharmacological effects can be used to increase the influence of disorders or to detect adaptive mechanisms. During the pharmacological therapy with carbamazepine or diphenylhydantoin, adaptive processes can be measured. PMID- 8495653 TI - Canine distemper myoclonus and sleep: observation of a case. AB - Evolution of myoclonus was analysed electromyographically throughout quiet wakefulness, NREM sleep and REM sleep in a dog with canine distemper myoclonus. Compared with quiet wakefulness, the frequency of myoclonus was decreased and the intensity of discharges in individual myoclonic bursts was also lowered during NREM sleep. When NREM sleep shifted to REM sleep, neither of these parameters was noticeably altered. However, as REM sleep continued, the former was increased markedly and the latter was further attenuated. In general, violent motor activity was concurrent in the limbs, trunk and/or head. Thus, the increase in the frequency of myoclonus seemed to be similar in nature to the phasic event during REM sleep. This indicated that lower motoneurons producing myoclonic discharges responded well to supraspinal influences. In successive myoclonic bursts, a significant and consistent positive correlation existed between the silent period and the subsequent discharge period throughout the three different levels of consciousness, that is, the longer the silent period, the longer the subsequent episode of myoclonus. Therefore, this feature may be intrinsic to myoclonic firing of lower motoneurons in canine distemper myoclonus. These findings may support the idea that hyperexcitability of the lower motoneurons is primarily responsible for the genesis of canine distemper myoclonus. PMID- 8495654 TI - Somatosensory evoked potentials during compound thumb movement. AB - The aim of the study was to assess the influence of a biphasic flexion-extension movement upon somatosensory evoked potentials (SEPs). Voluntary thumb flexion initiated a sequence of either single or single PLUS sustained electrical stimulation upon the median nerve. In cases of sustained stimulation the subjects had to overcome the induced tetanic thumb flexion. During movements the latencies of early components were longer compared to rest; during simple movements the amplitudes of most components were diminished compared to rest; the amplitudes of early components were further diminished in movements against tetanic contraction compared to simple ones; the suppression of SEP amplitudes was similar regardless of possibility to overcome the opposing tetanic contraction; the changes in SEP amplitudes were not dependent on training. PMID- 8495655 TI - Electromyographic analysis of effort in grip strength assessment. AB - The purpose of the present research was to investigate the use of surface EMG in assessing effort while measuring grip strength with the Jamar dynamometer. We hypothesized that sincere, maximal grip contractions could be distinguished from feigned, submaximal contractions by differences in the amplitude and frequency content of the EMG, as well as by differences in force. Healthy subjects (seven men and ten women) were instructed on different trials to give a sincere (maximal, 100%) effort or a feigned (50% of maximal) effort with the right hand. The subjects were tested at each of the five handle positions of the Jamar dynamometer. Surface EMG was obtained for the right palmaris longus/flexor carpi radialis muscles. Consistent with previous research, we found that the 50% efforts, compared to 100% efforts, showed, (1) lower peak force; (2) a slower rise to peak force; and (3) a different pattern of force measurements as a function of handle position. Feigned and sincere efforts also differed in the EMG. As hypothesized, amplitude was lower for 50% than 100% efforts. The frequency spectra of the EMG were obtained by Fourier analysis. The 50% efforts showed a higher frequency EMG than did the 100%. The results supported the hypothesis that surface EMG may provide a measure of effort in a grip strength task. Analysis of the EMG, in conjunction with force analysis, has the potential of being a valuable tool for the clinician needing to determine whether a patient is giving a sincere, maximal effort or is feigning. PMID- 8495656 TI - Evoked potentials obtained with tendon percussion in hemiplegic patients. AB - The purpose of this research was to verify in a group of hemiplegic subjects the usefulness of potentials obtained with tendon tap by evaluating the integrity of the proprioceptive area in relation to lesions in the middle cerebral artery territory. The healthy and paretic sides in 10 subjects affected by hemiplegia have been studied using the cerebral potential evoked by tendon tap. Two sets of 150 stimuli for each lower limb were applied at a standard repetition rate of 1 stimulus per 16 seconds. Data obtained shows a reduction of the amplitude of the P1-N1 cortical complex derived from the paretic side. This effect appears to be related to the entity of the kinaesthetic sensitivity impairment. PMID- 8495657 TI - Influence of head position on dorsal neck muscle efficiency. AB - The aim of this study was to assess the influence of head position on dorsal neck muscle efficiency in the sagittal plane. Fifteen subjects participated. The EMG versus isometric extension moment of dorsal neck muscles was studied in neutral (with subject gazing on a horizontal plane), cervical flexed, and cervical extended positions. A vectorial construction was created by means of photographs to calculate the extension moment which balances measured pulling force and gravitational force in isometric conditions. The maximum extension was highest in neutral position. The EMG/moment relationship was non-linear. The ratio between the EMG and the generated moment differed significantly in the three positions (p < 0.01) and was lower in neutral position. These results demonstrate the influence of head position on dorsal neck muscle efficiency; muscles appeared most efficient in neutral position. Muscle length, depending on head position, is probably the main influencing factor. PMID- 8495658 TI - Multimodality evoked potentials in sporadic amyotrophic lateral sclerosis: a statistical approach. AB - The involvement of sensory pathways in patients suffering from amyotrophic lateral sclerosis (ALS) is well reported in histopathological studies. Several laboratories have also used evoked potentials to evidentiate subtle dysfunctions of sensory systems in such patients. However, conflicting results have been presented in studies using evoked potentials. In the present experiment we have evaluated multimodality evoked potentials in subjects with sure diagnosis of sporadic ALS, by means of the Bonferroni multiple comparisons procedure. Our principal findings are: a) no statistical difference between patients and controls in BAEP and VEP recordings; b) a reduction of N13 amplitude and a prolonged P22 latency in SEP recordings. Due to the sources of N13 and P22, these latter alterations, however, do not implicate the involvement of somatosensory pathway. In conclusion, the current investigation does not provide an electrophysiological support for the involvement of sensory systems in the sporadic ALS. PMID- 8495659 TI - EMG-LAB computer system for routine electromyography. AB - The new computer aided program for fully automatic single MUAPs and IP analysis is described. This software programs called EMG-LAB represents the integrated system of IBM PC/AT computer with any kind of EMG machine. The individual MUAPs are automatically extracted, identified and measured on line, thanks to the sophisticated program based on statistical averaging. All the measured parameters like duration, amplitudes, areas, turns and phases are presented in computer display in a form of histograms. The summary of complete examination are presented in six parameters in form of histograms together with statistical values representing their distribution and variability. Those histograms represent the MUAPs waveforms remodeled during different disease processes. During maximum voluntary effort the interference pattern analysis is made on the new developed method. It allows to determine the parameters of different MU size, their quantity and intensity of recruitment. The most specific feature of this analysis concerns the information of the background activity, where the indirect data of single MUAPs and their parameters typical for given pathology could also be evaluated from interference pattern. PMID- 8495660 TI - Effects of external load and abduction angle on EMG level of shoulder muscles during isometric action. AB - Goal of the study was to investigate the effect of muscle length and load on EMG of shoulder muscles. Surface EMG's were taken of seven subjects during isometric abduction. One maximal and three submaximal tasks were performed. The force was always at right angles to the arm. Arm and electrode position were carefully standardized. EMG's for most muscles appeared to rise with increase in abduction angle for submaximal loads. Many different patterns were found at maximal load. Intertrial variation was quite acceptable. For pectoralis major the part from 90 to 135 degrees EMG curve becomes increasingly steeper with load. This is likely to be due to an increase of the lordosis of the lumbar spine as loads become heavier. The pectoralis major gets an adequate leverage to contribute to the task when the upper part of the thorax is tilted backwards. It is suggested that, because we do not know whether movements, relative muscle activation and force length relation are the same when submaximal and maximal contractions are compared, it is not advisable to use MVC's for normalisation purposes in shoulder EMG research. PMID- 8495661 TI - Formaldehyde-induced airway hyperreactivity in vivo and ex vivo in guinea pigs. AB - Human exposure to formaldehyde is extensive, in both the indoor and the outdoor environment. The airways are clearly an important site of action of formaldehyde. Although many previous studies have examined the effect of formaldehyde in the upper respiratory tract, it remains controversial whether this compound can affect the lower respiratory tract. To determine whether formaldehyde induces airway hyperreactivity, guinea pigs were exposed to formaldehyde or filtered air (sham control) for 2 or 8 hr. Airway smooth muscle responsiveness was evaluated in vivo and ex vivo. Specific pulmonary resistance and airway reactivity (to infused acetylcholine) increased with formaldehyde exposure. Formaldehyde exposure caused bronchoconstriction and hyperreactivity at lower concentrations when exposure duration was extended from 2 to 8 hr. Exposure to > or = 0.3 ppm formaldehyde for 8 hr was sufficient to produce a significant increase in airway reactivity, while similar effects only occurred after > 9 ppm formaldehyde for 2 hr. Formaldehyde exposure also heightens airway smooth muscle responsiveness to acetylcholine (or carbachol) ex vivo. These effects occurred with no evidence of epithelial damage or inflammation up to 4 days after formaldehyde exposure. Thus, at concentrations relevant to environmental exposure, formaldehyde, a common indoor air pollutant, alters airway smooth muscle reactivity in guinea pigs. These findings suggest that the duration of exposure is important to the induction of airway hyperreactivity and that prolonged, low-level exposures may generate abnormal physiological responses in the airways not detectable after acute exposures. PMID- 8495662 TI - Perinatal toxicity associated with nickel chloride exposure. AB - Several reports have suggested that soluble nickel salts may affect development. In this study female Long-Evans rats drank nickel chloride solutions (0, 10, 50, or 250 ppm Ni) for 11 weeks prior to mating and then during two successive gestation (G1, G2) and lactation (L1, L2) periods. Pups were observed until weaning; breeder males were unexposed. Dams drinking 250 ppm consumed less liquid and more food per kilogram body weight than did controls (liquid: prebreeding, G1, and G2; food: prebreeding, G2 and L2). Maternal weight gain was reduced during G1 in the high- and middle-dose groups; indices of reproductive performance were comparable across groups. Pup birth weight was unaltered by treatment and weight gain was reduced only in male pups exposed to 50 ppm Ni during L1. The frequency of perinatal death is the most significant toxicologic finding of the study. The proportion of dead pups per litter was significantly elevated at the high dose in L1 and at 10 and 250 ppm in L2 (50 ppm, P = 0.076), with a dose-related response in both experimental segments. The number of dead pups per litter was significantly increased at each dose in L2. Prolactin levels in pups were unchanged by treatment and were reduced in dams at the high dose. We conclude that 10 ppm Ni represents the lowest observed adverse effect level (LOAEL) in this study. PMID- 8495663 TI - Mercury contents of indicators and target organs in rats after long-term, low level, mercury vapor exposure. AB - Five groups of Wistar rats received graded concentrations of mercury vapor from 10 to 100 micrograms Hg/m3 6 hr, 5 days a week, from 4 to 11 weeks of age. One group breathing ambient air served as controls. The mercury levels of the indicators blood, hair, molars, and incisors as well as the target organs kidney cortex, cerebrum, cerebellum, liver, lung, spleen, tongue, and femur were measured by cold-vapor atomic absorption spectrophotometry. The mercury vapor had no negative influence on the weight gain of the animals. The results showed that the kidney cortex had the highest concentration of mercury. The mercury contents of all the indicators and all the target organs, with the exception of femur, were positively and significantly correlated with the exposure concentration. The rat molars had the highest correlation coefficient with the kidney mercury values, but no indicator had a significant correlation with all target organs. Rat molars are to some degree comparable to human deciduous teeth regarding time of mineralization and eruption. Based on the results presented in this study, we tentatively suggest that human deciduous teeth can be useful indicators of chronic mercury exposure not only at the exposure concentration level, but also as indicators of the mercury uptake in organs such as kidney and cerebrum. PMID- 8495664 TI - Modulation of macrophage-mediated cytotoxicity by kerosene soot: possible role of reactive oxygen species. AB - The involvement of reactive oxygen species (ROS) in the cytotoxicity of soot on rat alveolar macrophages has been postulated. A single intratracheal injection of soot (5 mg) in corn oil significantly induced the macrophage population, hydrogen peroxide (H2O2) generation, thiobarbituric acid (TBA)-reactive substances of lipid peroxidation, and the activities of extracellular acid phosphatase (AP) and lactate dehydrogenase (LDH) at 1, 4, 8, and 16 days of postinoculation. The activities of glutathione peroxidase (GPX) and catalase (CAT) were significantly inhibited at all the stages, while glutathione reductase (GR) and glucose-6 phosphate dehydrogenase (G6PD) showed a different pattern. These results show that soot is cytotoxic to alveolar macrophages and suggest that ROS may play a primary role in the cytotoxic process. PMID- 8495665 TI - Brain imaging techniques applied to chronically solvent-exposed workers: current results and clinical evaluation. AB - The application of neuroimaging techniques such as cerebral blood flow (CBF), single photon emission tomography (SPECT), X-ray computed tomography (CAT), and magnetic resonance imaging (MRI) on solvent-exposed workers and patients with toxic encephalopathy results in different and somewhat inconclusive pictures. The aim of this paper is to therefore critically review the current knowledge on chronic neurotoxicity of solvent exposures with respect to neuroimaging technique. CAT measurements of 86 house or construction painters, 82 spray painters, and 81 nonpainters showed no abnormal diffuse brain atrophy due to chronic solvent exposure after controlling for confounding variables such as age, alcohol consumption, or former disease. Correlation analyses did not show any consistent, biologically plausible exposure-effect relationship. Neuropsychologic test results did not correlate significantly with CAT parameters, whereas a strong age dependency exists. It is concluded that long-term exposure to solvent concentrations not exceeding permissible occupational limit values does not cause increased brain atrophy. PMID- 8495666 TI - Prevalence of abnormal neurobehavioral scores in populations exposed to different industrial chemicals. AB - The aim of the study is to establish the prevalence of neurobehavioral scores of occupationally exposed subjects below the 10th percentile rank of normalized curves obtained on a referent population. The Milan Automated Neurobehavioral System (MANS) was administered to 400 drivers from public and private firms; their data were distributed on the basis of age and years of school attendance and were normalized by determining percentile rank equivalence. The exposed population is made up of 20 lead- and zinc-exposed subjects, 18 welders exposed to aluminum for less than 1 year, 150 exposed to different metals in the ferromanganese production, 73 lithographic operators exposed to gasoline and petroleum, 197 exposed to solvents mixtures in the paint manufacture, and 23 dropouts of the same firm. The percentages of scores below 10th percentile rank were calculated in the different exposure groups and in the different age-school attendance ranges. The prevalence of results below the 10th percentile rank was found to be related to the intensity of the exposures and to the low levels of school attendance. In the 20-29 and the 30-39 age ranges, there was a prevalence of POMS scale scores below 10th percentile rank, in the 50-59 age range, the percentages were high for the Digit Symbol, the mean value of Simple Reaction Time, Serial Digit Learning, and Benton Visual Recognition. PMID- 8495667 TI - Relationships between health status and working conditions and personalities among VDT workers. AB - A total of 486 visual display terminal (VDT) workers were surveyed on their health status, working conditions, type A state, and depression state through questionnaires. They were also divided into three groups by self-assessment: technocentered (TC), technoanxious (TA), and neither (N). The weekly working hours and daily VDT operating hours of the type A group were longer than those of non-type A group. Type A subjects had more symptoms than non-type A subjects. The mean weekly working hours of depressive group was 61.3 hr, much longer than that of the others. The TC subjects worked daily with the VDT for longer hours than the other subjects. The TA subjects felt most dissatisfied with their computer training (TC, 47.4%; N, 64.5%; TA, 91.7%). Awkward VDT operators were more often in the TA group (36.1%) than in the others (TC, 3.8%; N, 10.5%). The TA subjects had a higher previous history of duodenal ulcer than the others (TA, 13.9%; N, 4.6%; TC, 3.8%). PMID- 8495668 TI - Occupation and the prevalence of major depression, alcohol, and drug abuse in the United States. AB - These data from the ECA research program clearly indicate considerable variation in prevalence among different occupational groups in the United States for major depression, alcohol abuse/dependence, and drug abuse/dependence. For example, the crude lifetime prevalences for depression ranged from 0.7 to 8.6 per 100; for alcohol it was 7.5 to 32.6, and for drugs it was 3.1 to 10.5. The results also indicate that some occupations are associated with much higher rates of ADM problems. By way of illustration, the 6-month crude prevalence of major depression for the total sample of employed persons 18-64 years of age was 2.9. Six of the occupational groups had prevalences which exceeded this rate. The overall 6-month prevalence of alcohol abuse/dependence was 5.8, and six occupational groups had prevalences in excess of this. Similarly, the overall 6 month prevalence was 2.6 for drug abuse/dependence, and five occupational groups had prevalences which exceeded this. Translated into terms of relative risk, it is clear that among the occupational groups some are at markedly increased risk of ADM disorders. For these comparisons, we used as the baseline group in logistic regression analyses, Job 1, composed of executive, administrative, and managerial occupations. This group is the first in the Census classification, had crude rates near the overall prevalence rates for depression, alcohol, and drugs, and is also one of the occupational categories with the highest prestige. Logistic regression analyses were done with and without controls for differences among occupational groups in gender, age, and educational level. As might be expected, adjustment in general narrowed differences in prevalence among occupational groups, and even on occasion, changed the rank order of groups slightly. However, in general, those groups with higher odds ratios based on crude rates also had higher adjusted odds ratios. Table 6 summarizes our findings, based on the adjusted odds ratios. In this table, we list occupational groups which had a relative risk of 30% or greater above baseline (Job 1), for both 6 month and lifetime prevalences, for each of the three ADM disorders. As can be seen, there is virtually no overlap between risk of depression, on the one hand, and risk of alcohol or drug abuse. The exceptions are Job 4 (sales) which ranked third for major depression and second for alcohol abuse in terms of 6 month prevalence, and Job 9 (farming, fishing, forestry), which had the [table: see text] highest lifetime risk for major depression and the second-highest 6 month risk for drug abuse/dependence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8495669 TI - Research program for neurotoxic disorders and other adverse health outcomes at hazardous chemical sites in the United States of America. PMID- 8495670 TI - Multidimensional assessment of mental state in occupational health care--combined application of three questionnaires: Tokyo University Egogram (TEG), Time Structuring Scale (TSS), and Profile of Mood States (POMS). AB - We attempted to develop a brief test battery to assess mental state for use in occupational health care settings. As a first step, we focused on the following three psychosocial aspects: ego state, behavioral pattern, and mood state which were considered to be closely related to mental state. To evaluate these parameters, we selected three established self-rating questionnaires: the Tokyo University Egogram for ego state, the Time Structuring Scale for behavioral pattern, and the Profile of Mood States for mood state. The combination of these three questionnaires was applied on 300 healthy company employees and school teachers (170 males and 130 females). Five ego-state factors (Critical Parents, Nurturing Parents, Adult, Free Child, and Adapted Child), five behavioral pattern factors (Withdrawal, Rituals and Pastimes, Activities, Intimacy, and Games), and six mood state factors (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment) were scored. Of 85 correlations between test factors, 49 in males and 61 in females were not significant, indicating that each test in this battery assessed aspects of mental state rather independent of those assessed by the others. However, significant correlations (P < 0.05) were observed for remaining pairs of test factors, indicating that these three parameters were also interrelated with each other, indicating that mental state could be elucidated more comprehensively by assessing all three psychosocial parameters than by assessing only one. The possibility that this battery could be used in the future in worksite health promotion programs is discussed. PMID- 8495671 TI - Relations between lead exposure and peripheral neuromuscular functions of lead exposed workers--results of tapping test. AB - In this study, four experiments using the tapping test were conducted to evaluate the possible subclinical effects of lead exposure on the neuromuscular systems of lead workers at some transfer printing factories in Japan. Decreases in the tapping ability appeared coincidentally with higher blood lead levels. The recovery of the tapping ability after 30 sec rest in the groups of 30-45 micrograms/dl and above 45 micrograms/dl PbB was worse than that in the group with less than 29 micrograms/dl PbB. The recovery of the decreased tapping ability after 60 sec rest was better even in the group with 30-45 micrograms/dl PbB. The tapping ability for 0-10 sec at the first tapping test was sustained after 30 or 60 sec rest in the group with the PbB below 29 micrograms/dl; however, the tapping ability at the second and third tapping test decreased in the two groups with the PbB level above 30 micrograms/dl. The decreased finger tapping speed may be functional evidence of low-grade motor neuropathy among the workers with higher levels of lead absorption. PMID- 8495672 TI - Radial and median nerve conduction velocities in workers exposed to lead, copper, and zinc: a follow-up study for 2 years. AB - To evaluate the interactive effects of lead, zinc, and copper on the peripheral nervous system in man, we measured maximal motor and sensory conduction velocities (MCV and SCV) in the distal radial and median nerves in 19 gun metal foundry workers with asymptomatic increased absorption of these metals twice at a 12-month interval. The workers' initial blood lead (BPb) concentrations ranged from 16 to 64 (mean, 42) micrograms/dl. The principal findings in the present study indicated that (1) radial and median nerve conduction velocities were significantly slowed in the gun metal foundry workers; (2) indicators of lead absorption were inversely related to radial nerve conduction velocities, whereas indicators of copper and zinc absorption were positively correlated with the radial and median nerve conduction velocities; and (3) yearly changes in MCV in the radial nerve and in SCV in the median nerve were positively correlated with the changes in indicators of copper and zinc absorption. These findings suggest that zinc and copper antagonize the subclinical neurologic effects of lead. Also, the radial and median nerve conduction velocities provide important indicators of subclinical lead toxicity. PMID- 8495673 TI - Assessment of the distribution of nerve conduction velocities in alcoholics. AB - To assess the effects of chronic alcohol ingestion on the faster and slower nerve fibers (alpha fiber group) in the peripheral nervous system, the distribution of nerve conduction velocities (DCV) and conventional maximal motor and sensory nerve conduction velocities (MCV and SCV) in the median nerve were measured in 23 male patients with severe alcoholic dependency (DSM-III-R), aged 30-64 (mean, 50) years, and in 23 age-matched healthy men. The DCV was expressed by the conduction velocities below which 10, 20,..., 80, and 90% of active fibers lie (V10, V20,..., V80, and V90 velocities). The V40 to V90 velocities of the DCV were significantly slower in the alcoholics than in the control subjects; the SCV and MCV in the alcoholics were also significantly slowed. These findings suggest that the faster large myelinated nerve fibers are more sensitive to chronic alcohol ingestion than the slower large myelinated nerve fibers. PMID- 8495674 TI - Assessment of central, peripheral, and autonomic nervous system functions in lead workers: neuroelectrophysiological studies. AB - To assess the effects of lead on central, peripheral, and autonomic nervous systems, the visual-, short-latency somatosensory-, and brainstem auditory-evoked potentials (VEP, SSEP, and BAEP), event-related potential (P300), distribution of nerve conduction velocities (DCV), and electrocardiographic R-R interval variability (CVRR), together with conventional median and radial nerve conduction velocities (NCV), were measured in the lead workers. The lead workers consisted of 22 gun metal foundry workers occupationally exposed to lead, zinc, and copper. In the lead workers with blood lead concentrations below 65 micrograms/dl, the latencies of the VEP (from the retina to the visual cortex), SSEP (from the brachial plexus to the brainstem), and P300 (which reflects cognitive function) were significantly prolonged when compared with the sex- and age-matched controls. All these latencies and the BAEP latencies (from the cochlear nerve to the brainstem) were significantly correlated with the indicators of lead absorption among these workers. The CVRR (especially, a component of parasympathetic activity) was significantly depressed in the lead workers. The slower (V10) velocity of the DCV, the motor, and sensory NCVs were also significantly slowed. These findings suggest that lead affects not only peripheral nerve but also the central and autonomic nervous functions at a subclinical level; zinc may antagonize the neurotoxic effects of lead. PMID- 8495675 TI - Effect of some factors on sleep polygraphic parameters and subjective evaluations of sleep. AB - In this study a bedroom in a noisy area and one in a quiet area were used to investigate the effects of road traffic noise on sleep. Subjective sleep and objective sleep polygraphic parameters were obtained from subjects sleeping in each bedroom. Differences in these parameters at the two locations were compared. The experimental environment differed from those formerly used. The authors thus examined the influences on sleep of covariates in terms of subject differences, age differences, sex difference, differences in the order of experimental nights, set differences, and noise differences. From Spearman's rank correlation coefficient and two-way analysis of variance, subject and age differences were found to have greater effects on many sleep parameters than noise differences. Principal factor analysis was done for young and old subjects separately. The sixth factor was related to noise differences. The sleep parameter common to young and old subjects of the sixth factor was %REM. PMID- 8495676 TI - Adaptation of the WHO NCTB for use in Poland for detection of effects of exposure to neurotoxic agents. AB - The purpose of the project was an assessment of psychometric characteristics of the WHO Neurobehavioral Core Test Battery (NCTB) (in traditional version) and the Hanninen Subjective Symptom Questionnaire adapted for Poland. The subjects were 119 greenhouse workers, 65 of them were exposed to organophosphorous pesticides and 54 were nonexposed ones. To assess the reliability, all tests from NCTB were administered twice with a 4-month interval. The results obtained in the first examination were used to determine the effects of gender, age, and education on tests performance. To determine the underlying factor structure of the test battery, the factor analysis was performed on 45 variables. The test-retest reliability coefficients ranged from 0.33 to 0.91. The lowest correlations were found for the Aiming Test--sum of errors (r = 0.33) and the Benton Test (r = 0.34). Gender appeared to be the most modifying factor of test performance. The factor analysis yielded 11 factors with eigenvalues greater than 1.0 (78.4% of variance explained). PMID- 8495677 TI - Measurement of vibratory perception threshold (VPT) in workers exposed to organic solvents. AB - Vibratory perception threshold (VPT) of 437 workers exposed to organic solvents in various industries was measured using an automated device, Vibrometer TM-31A, at the medial malleolus of the right leg. There were statistically significant correlations between age and VPT (rs = 0.378, P < 0.01) and job experience and VPT (rs = 0.125, P < 0.01). Fifty-five out of 437 examinees showed abnormally higher VPT than the previously reported control values, suggesting an existence of potential neuropathy in these individuals. There was no significant correlation between the amount of urinary metabolites and VPT. Neither specific exposure-related subjective symptoms nor clinical neurological signs were found in any workers. The study also discusses the validity of and the future problems in measuring VPT in workers exposed to solvents. PMID- 8495678 TI - Experimental studies on brain oedema after blunt head injury: experimental approaches from animal experimentation to actual or possible clinical application. PMID- 8495679 TI - Neonatal wellbeing after elective caesarean delivery with general, spinal, and epidural anaesthesia. AB - A comparison was made of the acid-base and Apgar status of neonates following general (n = 34), spinal (n = 28) and epidural (n = 23) anaesthesia for elective caesarean section. Neonates delivered following spinal anaesthesia were more acidaemic (pH = 7.249) (P < 0.05) than those delivered following epidural (pH = 7.291) or general anaesthesia (pH = 7.296) despite measures taken to minimize hypotension. The percentage of neonates with a 1 min Apgar score > or = 7 was 96% after epidural anaesthesia, 93% after spinal anaesthesia and 75% after general anaesthesia. The difference between epidural and general anaesthesia was significant (P < 0.05). Using these two measures of neonatal wellbeing, epidural anaesthesia provided the most favourable outcome. PMID- 8495680 TI - Epidural analgesia for labour using a continuous infusion of bupivacaine and alfentanil. AB - Seventy women who requested epidural pain relief in labour received a continuous epidural infusion at 8 ml h-1, which contained either 0.25% bupivacaine (n = 29), or a mixture of 0.125% bupivacaine and 0.005% alfentanil (n = 31), assigned randomly. Increments of 4 ml 0.25% bupivacaine were given on demand to prevent residual pain from uterine contractions. The two groups were compared for motor block of the lower limbs, number of increments required, type of delivery and neonatal Apgar scores. The group of women receiving the mixture of bupivacaine and alfentanil required between them seven increments; the group receiving bupivacaine alone required 15. One of the women receiving the mixture and eight of the women receiving bupivacaine alone had almost complete motor block. There were no differences in the mode of delivery or in the neonatal Apgar scores. PMID- 8495681 TI - Immunological and hormonal responses to lung surgery during one-lung ventilation. AB - The effects of lung surgery performed during one-lung ventilation and the associated endocrine stress response on natural killer (NK) cell activity and the distribution of white blood cells in peripheral blood were studied in 10 patients with malignant lung tumours. Patients were anaesthetized with general anaesthesia combined with thoracic epidural anaesthesia. The endocrine response was measured as changes in serum cortisol, plasma adrenaline and noradrenaline. A significant decrease of NK cell activity was found post-operatively accompanied by leucocytosis, neutrophilia and lymphopenia. Significant increases in serum cortisol were demonstrated at the end of operation and throughout the study period. Plasma adrenaline increased significantly during one-lung ventilation with a gradual normalization post-operatively. Plasma noradrenaline increased significantly during the whole post-operative course. In conclusion, lung surgery was accompanied by similar changes in NK cell activity, leucocyte and differential counts, serum cortisol and plasma adrenaline levels as demonstrated after other types of major surgery. The elevated noradrenaline level post operatively is a new observation that may be specific for lung surgery. PMID- 8495682 TI - Comparison of omeprazole with cimetidine for prophylaxis of acid aspiration in elective surgery. AB - Gastric pH and volume were measured in four groups of 15 patients scheduled for elective surgery. The patients were randomly allocated to receive either no antacid, oral omeprazole 40 mg the evening before surgery, oral omeprazole 40 mg 2 h before surgery, or effervescent cimetidine 800 mg, 2 h before surgery. Anaesthesia was induced with thiopentone (4-6 mg kg-1), fentanyl (0.03 mg kg-1) and vecuronium (0.1 mg kg-1) and maintained with nitrous oxide in oxygen (50/50) and isoflurane. After induction of anaesthesia and on completion of surgery, gastric pH (mean +/- SEM) and volume were measured using a glass electrode and a phenol red dilution technique. Gastric pH were significantly higher in the three treated groups than in control (P < 0.01). Omeprazole and cimetidine were equally effective in reducing volume and pH of the gastric juice at the beginning and at the end of anaesthesia. Nevertheless 14.2 and 28.5% of patients who received omeprazole respectively the day before or the morning of surgery remained at risk of aspiration pneumonitis (gastric pH < 2.5 and gastric volume > 25 ml). PMID- 8495683 TI - Blood volume at the onset of hypotension during TURP performed under epidural anaesthesia. AB - An analysis was made of the development of hypotension in the course of 60 transurethral resections of the prostate (TURP) performed under epidural anaesthesia. Hypotension was defined as a decrease in the systolic pressure down to 85 mmHg or less, or a total drop of 60 mmHg or more within 15 min. Indirect estimations of the blood volume according to the haemoglobin dilution method indicated that patients who developed hypotension from the epidural anaesthesia had a larger decrease in blood volume than other patients. During the operation, hypotension was associated with a blood volume of 300 ml or more below baseline, while 400 ml above baseline was required to ensure a stable circulation when the legs were lowered and removed from the stirrups after the TURP. Low central venous pressures, which were measured in 30 of the patients, were also associated with hypotension during and after TURP. There was a significant linear relationship between the total changes in blood volume and CVP measured at the end of each 10-min period of TURP (P < 0.001). However, no correlation between heart rate and hypotension was found. PMID- 8495684 TI - Is normal saline an acceptable alternative to silicone for lubricating fibrescopes? AB - This article describes a model designed to measure the forces acting on a fibrescope when it is pushed through an endotracheal tube. Lubrication with either silicone or normal saline leads to a reduction in friction forces. Fibrescopes lubricated with normal saline require a larger force to be advanced through endotracheal tubes when compared to silicone; however, the difference is clinically unimportant and is outweighed by the advantageous properties of normal saline. A theoretical model is presented which is in close agreement with experimentally derived data. PMID- 8495685 TI - Intra-hospital transport of the anaesthetized patient. AB - This study evaluated the anaesthetic management of 20 patients, undergoing intra operative radiation therapy for pancreatic or rectal tumours. Patients with a re approximated surgical incision were transferred from the operating room to the radiotherapy department while still under anaesthesia. The risks of such transport as well as guidelines for the patient's care during this phase are examined. The results of this study indicate that in order to transport anaesthetized patients safely it is necessary to ensure stable cardiovascular, respiratory and metabolic conditions prior to their transfer. It is also important to guarantee adequate analgesia and to establish appropriate monitoring during transport. PMID- 8495686 TI - Octreotide and dependence on ventilatory support. PMID- 8495687 TI - Possible role of thymol in the pathogenesis of 'halothane hepatitis'. PMID- 8495688 TI - Muscle length-force characteristics in relation to muscle architecture: a bilateral study of gastrocnemius medialis muscles of unilaterally immobilized rats. AB - The geometry of rat gastrocnemius medialis muscle (GM) was studied at different muscle lengths. In addition, the number of sarcomeres in series within fibres was estimated. For muscles of immobilized legs (i.e. GM was held at in vivo smallest length) as well as those of the contralateral legs, comparison was made with controls of similar age. Immobilization periods of 4 and 6 weeks were used. For immobilized GM muscles, the number of sarcomeres in series was lower only within distal fibres after 4 weeks of immobilization. Aponeuroses were 25% shorter after both immobilization periods and no differences were found for fibre and aponeurosis angle. For GM of contralateral legs no difference with respect to controls was found regarding the number of sarcomeres in series. Aponeuroses were approximately 15% shorter and the fibre and the aponeurosis angle were also smaller. Based on these geometrical differences, it was expected that both experimental muscles should exert force over a smaller range of muscle length than controls. However, for immobilized muscles a similar range of length was found for which a possible explanation could be the more compliant aponeurosis. For contralateral muscle a 2-mm larger length range as well as a change of distribution of optimal fibre length with respect to optimal muscle length was found. For immobilized muscles indications of a distribution of optimal fibre lengths were also found but these did not differ from those of the controls. The results for contralateral muscles would indicate that the distribution may be changed under the influence of an altered use of the limb and that this may be an important factor determining the length range of active force generation. PMID- 8495689 TI - Effects of body morphology and mass on thermal responses to cold water: revisited. AB - Seven male volunteers were divided into two groups based on body morphology and mass. The large body mass (LM) group (n = 4) was 21.2 kg heavier and 0.32 m2.kg-1 smaller in surface area-to-mass ratio (P < 0.05) than the small body mass (SM) group (n = 3). Both groups were similar in total body fat and regional skinfold thicknesses. All subjects were immersed to the first thoracic vertebrae for 120 min in stirred water at 18 degrees C. Overall, tissue insulation was similar (P > 0.05) between the SM and LM groups across time. Perceptual ratings of thermal sensation increased (P < 0.05) across time. Therefore, as cold water immersion progressed, tissue insulation was similar and thermal sensation increased (P < 0.05) in males matched for subcutaneous fat and total fat but differing in body mass and morphology. PMID- 8495690 TI - Basal concentrations of anabolic and catabolic hormones in relation to endurance exercise after short-term changes in diet. AB - This study aimed to use a classical model to analyse whether alterations in performance due to short-term changes in diet are reflected in peripheral basal anabolic and catabolic hormone concentrations. Six healthy students (two women and four men) performed a cross-over study including three test situations. The reference test was preceded by each subject's normal unrestricted diet of western type (N). After this, three of the subject's were provided a carbohydrate-rich diet (CHO) for 3 days followed by the second test. Following this test, a carbohydrate deficient, protein/fat rich diet (F) was provided for another 3 days followed by the third test. The remaining three subjects had these diets in reverse order. Basal concentrations of cortisol (C), sex hormone-binding globulin (SHBG), insulin-like growth factor (IGF-I), total-testosterone and non-SHBG-bound testosterone (NST), the NST:C ratio and an ergometer cycle endurance test with measurements of submaximal as well as measurements of maximal oxygen uptake, heart rate, respiratory exchange ratio (R), free fatty acids (FFA), glycerol and lactate were investigated. All the subjects were involved in athletics for recreation and during the study they performed daily physical exercise according to their normal routine. After the F diet only two of the subjects completed the test. One woman dropped out after 16 min, two men dropped out after 14 min and one after 13 min of cycling. After the CHO diet all six subjects completed the ergometer cycle test. Considering the whole group, there were no significant differences in lactate or glycerol concentrations during the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495691 TI - Relative contraction force producing a reduction in calf blood flow by superimposing forearm exercise on lower leg exercise. AB - The relative contraction force producing a reduction in exercise hyperaemia was studied by superimposing handgrip contraction at different intensities on plantar flexion of low intensity. Ten active women served as subjects. Blood flow to the forearm (Qforearm) and calf (Qcalf) was measured with mercury-in-rubber strain gauges by venous occlusion plethysmography immediately after 60 s of rhythmic plantar flexion at 10% of maximum voluntary contraction (MVC), which was expressed as P10H0, or combined plantar flexion and handgrip contraction. In the combined exercise, handgrip exercise at 30%, 50% or 70% MVC was added to plantar flexion during the last 30 s of exercise (P10H30, P10H50 and P10H70, respectively). The Qforearm increases after P10H30, P10H50 and P10H70 were significantly larger (P < 0.01) than that after P10H0, and the difference between P10H30 and P10H70 was also significant (P < 0.01). Immediate post-exercise Qcalf after P10H0 increased by 7.4 (SEM 0.9) ml x 100 ml-1 x min-1. When handgrip contraction at 70% MVC was added, the Qcalf increase after exercise [4.5 (SEM 0.7) ml x 100 ml-1 x min-1] was significantly lower than after plantar flexion alone (P < 0.05). However, no significant change was found in Qcalf when the forces of added handgrip contraction were 30% and 50% MVC, although the mean value of Qcalf increase was lower after P10H50 combined exercise. Calf vascular resistance calculated as BP/Qcalf (BP mean blood pressure) tended to increase after P10H70 to a nonsignificant extent. Heart rate and oxygen uptake in these exercises increased when handgrip contraction at 30%, 50%, or 70% MVC was added to plantar flexion at 10% MVC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495692 TI - Responses of intra-abdominal pressure and abdominal muscle activity during dynamic trunk loading in man. AB - The purpose of this study was to determine and compare interactions between the abdominal musculature and intra-abdominal pressure (IAP) during controlled dynamic and static trunk muscle loading. Myoelectric activity was recorded in six subjects from the rectus abdominis, obliquus externus, obliquus internus, transversus abdominis and erector spinae muscles using surface and intra-muscular fine-wire electrodes. The IAP was recorded intra-gastrically. Trunk flexions and extensions were performed lying on one side on a swivel table. An adjustable brake provided different friction loading conditions, while adding weights to an unbraked swivel table afforded various levels of inertial loading. During trunk extensions at all friction loads, IAP was elevated (1.8-7.2 kPa) with concomitant activity in transversus abdominis and obliquus internus muscles--little or no activity was seen from rectus abdominis and obliquus externus muscles. For inertia loading during trunk extension, IAP levels were somewhat lower (1.8-5.6 kPa) and displayed a second peak when abdominal muscle activity occurred in the course of decelerating the movement. For single trunk flexions with friction loading, IAP was higher than that seen in extension conditions and increased with added resistance. For inertial loading during trunk flexion, IAP showed two peaks, the larger first peak matched peak forward acceleration and general abdominal muscle activation, while the second corresponded to peak deceleration and was accompanied by activity in transversus abdominis and erector spinae muscles. It was apparent that different loading strategies produced markedly different patterns of response in both trunk musculature and intra-abdominal pressure. PMID- 8495693 TI - Assessment of exercise-induced alterations in body composition of patients with coronary heart disease. AB - The purpose of this study was to determine the effects of exercise habituation on body composition and anthropometric characteristics in cardiac patients. The subjects, comprising 20 patients with coronary heart disease, aged 43-69, participated in our supervised exercise programme for 38.0 (SD 12.5) weeks while in hospital. The intensity of most exercise was set at the lactate threshold. Analyses of the data indicated that small but significant reductions were observed in body mass (mb) [-1.4 (SD 1.8) kg], abdominal girth [-1.4 (SD 2.6) cm], chest girth [-1.3 (SD 1.8) cm], body mass index [-0.6 (SD 0.7)], and skinfold thicknesses at all the sites measured. As expected, fat-free mass, derived from either bio-electrical impedance (BI) or a skinfold technique with commonly used regression equations, remained essentially unchanged, while there were significant decreases in body fat (BF) and %BF. The absolute amount of change in mb (i.e. delta mb) was significantly associated with delta abdominal girth (r = 0.506), delta BF estimated by the BI technique (r = 0.476), and delta BF estimated by the skinfold technique (r = 0.451). Although the period of the exercise programme [38.0 (SD 12.5) weeks] varied greatly among subjects, it was found not to be associated with delta mb and alterations in body composition. We concluded that aerobic exercise induced significant decreases in BF and many anthropometric variables, independent of the duration of exercise, and that a combination of abdominal girth, BI and/or skinfold measurements would be advantageous in estimating primarily exercise-induced alterations in BF in cardiac patients. PMID- 8495694 TI - Responses of subjects with spinal cord injuries to maximal wheelchair exercise: comparison of discontinuous and continuous protocols. AB - Six male subjects with spinal cord injuries (SCI) participated in this investigation to compare peak values of oxygen uptake (VO2), heart rate (fc), ventilation (VE), respiratory exchange ratio (R) and power output (W) obtained using a discontinuous (DP) and a continuous jump max protocol (JMP) in a maximal wheelchair exercise test on a treadmill. The W increments were achieved by imposing an extra mass upon the wheelchair through a pulley system. The DP involved exercise periods of 3 min separated by 2-min intervals at relative rest. Increments in W consisted of 0.10 or 0.15 W.kg-1 total mass. During the rest intervals no mass was imposed on the wheelchair. The JMP involved an increase in W each minute. Increments and velocity in the JMP were the same as during the exercise periods for DP. Mean peak values for W [99.5 (SD 13.6) W], VO2 [2.13 (SD 0.27) l.min-1, standard temperature and pressure, dry], R [1.25 (SD 0.16)] and VE [82.8 (SD 11.2) l.min-1, body temperature and pressure, saturated] in DP were not different from values observed for W [103.5 (SD 13.1)], VO2 [2.18 (SD 0.31) l.min 1], R [1.17 (SD 0.16)] and VE [78.9 (SD 16.0) l.min-1] in the JMP. The only significant difference was observed for fc: 198 (SD 11) beats.min-1 in DP and 187 (SD 11) beats.min-1 in JMP. The higher values for fc elicited using DP have been discussed. It was concluded that both a DP and a JMP seem to be equally appropriate in determining peak VO2 and peak W in SCI persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495695 TI - Ventilatory responses to exercise and carbon dioxide in elderly and younger humans. AB - The present investigation examined the relationship between CO2 sensitivity [at rest (SR) and during exercise (SE)] and the ventilatory response to exercise in ten elderly (61-79 years) and ten younger (17-26 years) subjects. The gradient of the relationship between minute ventilation and CO2 production (delta VE/delta VCO2) of the elderly subjects was greater than that of the younger subjects [mean (SEM); 32.8 (1.6) vs 27.3 (0.4); P < 0.01]. At rest, SR was lower for the elderly than for the younger group [10.77 (1.72) vs 16.95 (2.13) l.min-1 x kPa-1; 1.44 (0.23) vs 2.26 (0.28) l.min-1 x mmHg-1; P < 0.05], but SE was not significantly different between the two groups [17.85 (2.49) vs 19.17 (1.62) l.min-1 x kPa-1; 2.38 (0.33) vs 2.56 (0.21) l.min-1 x mmHg-1]. There were significant correlations between both SR and SE, and delta VE/delta VCO2 (P < 0.05; P < 0.001) for the younger group, bot none for the elderly. The absence of a correlation for the elderly supports the suggestion that delta VE/delta VCO2 is not an appropriate index of the ventilatory response to exercise for elderly humans. PMID- 8495696 TI - The pressor response to involuntary isometric exercise of young and elderly human muscle with reference to muscle contractile characteristics. AB - Changes in heart rate (fc) and blood pressure (BP) were observed in eight healthy young men aged [mean (SD)] 20 (1) years and ten healthy elderly men aged 65 (5) years, during electrically evoked contractions of the ankle plantar flexors and elbow flexors which were sustained for 2 min. There was no significant difference in the fc response to evoked contraction of the ankle plantar flexors or elbow flexors between young and elderly subjects. During contraction of the elbow flexors, elderly subjects produced an unexpectedly large rise in systolic BP which was significantly greater than that of the young subjects. The exaggerated response seen in the elderly group may be due to a more rigid arterial tree which is thought to occur with advancing age. Electrically evoked contraction of the slower contracting elderly ankle plantar flexors resulted in a significantly diminished diastolic BP response when compared with that of the young subjects. In contrast, during electrically evoked contraction of the elbow flexors, which showed a similar twitch time course in young and elderly subjects, the diastolic BP response was not significantly different between groups. This may reflect differences in the peripheral reflex input to the pressor response in elderly arm and leg muscles which, in turn, may be influenced by relative fast twitch fibre area. PMID- 8495697 TI - A comparison of voluntary and electrically evoked isokinetic plantar flexor torque in males. AB - The angle-specific isokinetic torque- and power-velocity relationships of the triceps surae were examined in ten male sprint athletes aged [mean (SD)] 22.4 (3.2) years, ten non-trained adult men aged 27.4 (4.8) years and six elderly male subjects aged 68.5 (2.4) years. Normal voluntary contractions were compared with those obtained using maximal tetanic stimulation and a release technique which standardised the level of muscle activation during isokinetic contractions. When the isokinetic data was normalized to the maximum isometric torque the stimulated release contractions at 5.18-5.29 rad.s-1 produced significantly (P < 0.05) greater torque than the voluntary no-release contractions at the same angular velocity in each group of subjects. The three subject groups generated their peak power at 3.07 rad.s-1 during the voluntary no release contractions. However, with the stimulated release contractions, power had still not reached a peak at 5.29 rad.s-1, the highest angular velocity that could be tested. It appears that at higher angular velocities the triceps surae is capable of greater torque and power generation when contractions are evoked using a stimulated release technique. It is suggested that the stimulated release technique gives a more complete picture of the torque-velocity characteristics of the contractile component of the triceps surae. PMID- 8495698 TI - Amplitude and frequency measures of surface electromyography during dual task elbow torque production. AB - Studies of motor unit recruitment thresholds have demonstrated the existence of task-specific motor units within the muscles controlling the elbow. Two degree-of freedom (df) task specificity was investigated at higher levels of elbow torque using the amplitude and frequency characteristics of surface electromyography (EMG). Flexion and supination torque data were collected together with EMG from electrode pairs on the brachioradialis (BRAD), biceps brachii short head, and medial and lateral aspects of biceps brachii long head, while subjects (n = 14) performed the following four combinations of isometric tasks: (1) maximum voluntary contraction (MVC) flexion (F) and (2) MVC supination (S), each with a targeted torque of zero in the second df; (3) MVC flexion with targeted MVC supination (FS); and (4) MVC supination with targeted MVC flexion (SF). Median power frequency (MEDF) and root mean square (RMS) amplitude under steady-state torque conditions were calculated and analyzed using ANCOVA models with planned contrasts (alpha = 0.05). A significant main effect for task was found in RMS, but not in MEDF. Contrasts showed a significant increase in RMS response in the dual MVC tasks (FS and SF) over the single MVC tasks of F and S. The lack of frequency changes with alterations in RMS data indicates that the underlying recruitment/rate coding scheme in use for dual-df tasks may be different than in single-df tasks, and provides possible support for the notion of motor unit task groups. Task-by-site interactions were found for both MEDF and RMS, and illustrated that the three biceps sites differed from BRAD in their responses to the F versus S tasks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495699 TI - Melatonin and gonadotropin secretion after acute exercise in physically active males. AB - Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone, testosterone (T) and melatonin were measured in seven physically active male volunteers after exercise on a treadmill using the Bruce protocol. Measurements were made on blood samples obtained before exercise, within 30 s after exercise, at 15 min after exercise, and subsequently at 30-min intervals after exercise for a total duration of 180 min. Serum LH concentration fell from a peak post exercise level of 15.7 (4.7) IU.l-1 [mean (SD)] to a nadir of 10.3 (2.4) IU.l-1 (P < 0.004). Nadir values in individual volunteers were seen between 60 and 150 min after exercise. This fall in serum LH was paralleled by a similar fall in the concentration of serum T. Serum melatonin concentrations did not change significantly after exercise. It is concluded that melatonin, despite is reported anti-gonadotropic properties, does not play a role in the depression of serum LH after acute strenuous exercise in physically active males. PMID- 8495700 TI - Comparison of treadmill exercise testing protocols for wheelchair users. AB - The reduced early mortality and the increased life span of persons with spinal cord injury (SCI) and other chronically disabling conditions which result in loss of use of the legs places them at increased risk of coronary heart disease, diabetes, and hypertension. Exercise testing in this population is becoming more common, but there is a need for assessment of protocols in order to determine the best method to elicit a maximal response in a reasonable time without endangering the patient. Three wheelchair treadmill protocols were compared in seven men with paraplegia aged 21-44 years (five SCI, two post-polio). Subjects repeated each protocol to estimate reliability. Protocol G consisted of increasing treadmill grade at a constant speed (4.8 km.h-1); in protocol S, the speed was increased at a constant grade (0%), and in protocol C, speed and grade were increased. Two minute stages were used in all protocols. Peak oxygen uptake [VO2max; mean (SD): 23.6 (5.8) ml.kg-1 x min-1; 1.66 (0.37) l.min-1], VCO2 production [1.98 (0.46) l.min-1], ventilation volume [83.0 (25.6) l.min-1], respiratory exchange ratio [1.2 (0.12)], and heart rate [173 (18)] were determined. Over all trials none of the variables was significantly different among the three protocols, but all were highest in C and lowest in S. Reliability coefficients for absolute and relative VO2max ranged from 0.76 and 0.81 in G to 0.95 and 0.98 in C (all P < 0.05). These data suggest that an incremental treadmill test similar to the C protocol may be the optimal method to use when evaluating the exercise capacity of wheelchair users. PMID- 8495701 TI - Endocrine response to intense interval exercise. AB - This investigation provides an insight into the physiological changes produced, and processes operating, during and after a typical interval exercise training regime. The role of interval exercise in the modulation of the plasma concentration of sex hormone binding globulin (SHBG) and the hormones beta oestradiol, testosterone, prolactin and growth hormone was assessed. Eight trained male athletes [mean maximal oxygen uptake (VO2max) 64.3 (SD 3.8) ml.kg-1 x min-1, mean age 31.5 (SD 4.5) years] undertook an intense interval exercise (treadmill running) protocol to exhaustion. Subjects completed an average of 15.6 x 1-min runs. This interval protocol produced significant increase in the plasma concentration of SHBG and all four hormones (all P < 0.01) in the immediate post test period. The plasma concentration of the hormones increased as indicated: beta-oestradiol (45%), testosterone (38%), prolactin (230%), growth hormone (2000%). These hormones have an established capacity to interact with components of many physiological systems and, as such, may provide a mechanism for the changes induced by intense exercise in many of these systems. PMID- 8495702 TI - The relationship between short-term antibiotic treatments and fatigue in healthy individuals. AB - Antibiotic treatment tends sometimes to result in sensations of fatigue and decreased physical performance. The effects of antibiotics were therefore studied in 50 healthy, male trainees, aged 18-25 years, assigned in a random, double blind fashion to one of the following treatments: tetracycline, ampicillin, trimethoprim/sulphamethoxazole, placebo I and placebo II. Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly. Muscle enzyme activity (serum glutamine oxaloacetate transaminase, lactate dehydrogenase, creatine phosphokinase), maximal aerobic capacity (VO2max), muscle strength (MS), and rating of subjective sensation of fatigue were assessed prior to and upon conclusion of treatment. Compared to pretreatment values, plasma enzymes activity was elevated in all five groups (P < 0.005). No differences in VO2max or in MS were found among the subjects treated with either one of the antibiotics or those given a placebo. A significant difference in VO2max was found between the groups treated for 1 day (antibiotic and placebo) and the groups treated for 3 days (antibiotic and placebo) (P < 0.0001). The rating of subjective sensation was not affected by any of the agents. We concluded that in healthy individuals, a short-term antibiotic treatment had no deleterious effect on aerobic capacity or on muscle strength and was not associated with subjective side effects. The time interval between the two maximal tests could, however, have affected the aerobic capacity. Physiological disturbances associated with a sensation of fatigue following a longer period of antibiotics cannot be excluded. PMID- 8495703 TI - Changes in the characteristics of anaerobic exercise in the upper limb during puberty in boys. AB - The aim of this study was to examine the relationships between the characteristics of anaerobic exercise in the upper limb and important indicators of growth and developmental age such as height (h), body mass (mb), skeletal age (SA), plasma testosterone (T) and pubertal stage (PS). We used the force-velocity (F-v) relationship test in a population of 66 healthy adolescent male junior jockeys, with considerable variation in these indicators but of the same physical fitness level (training effect). The mean values of the maximal anaerobic power (Wan,max) were 391 (SD 93) W. The values of the variables in the F-v relationship for the upper limb were only slightly or uncorrelated with the chronological age, but highly correlated with h, mb and SA (P < 0.001). The correlation with T was less significant. Using ANOVA a highly significant effect of PS on the variables in the F-v relationship was found (P < 0.001). The absolute or relative (normalized to mb) increase in Wan,max during puberty was greater from PS P2 and P3 than at other stages. Therefore PS would appear to be a significant factor for developmental changes in anaerobic characteristics during puberty in the adolescent. The PS P3 determined only by public hair might be an easy and accurate indicator for sports category classification of adolescents during puberty. PMID- 8495704 TI - Growth factors prevent mitochondrial dysfunction, loss of calcium homeostasis, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose. AB - The mechanism of growth factor protection against metabolic/excitotoxic insults was examined. The time course of changes in ATP levels, mitochondrial transmembrane potential, intracellular free calcium levels ([Ca2+]i), and cell survival resulting from glucose deprivation were assessed in cultured hippocampal neurons. ATP levels were significantly reduced within 1 h of the onset of glucose deprivation and reached less than 20% of control levels by 12 h. Mitochondrial transmembrane potential (assessed by rhodamine 123 accumulation in mitochondria) declined progressively between 4 and 20 h following the onset of glucose deprivation. The [Ca2+]i was reduced during the first 1 h of glucose deprivation, gradually rose through 12 h, and then rose rapidly and was elevated five- to sevenfold after 16 h. The [Ca2+]i did not increase, and mitochondrial dysfunction and cell damage were prevented, in hypoglycemic neurons incubated in Ca(2+) deficient medium. Elevation of [Ca2+]i by exposure of neurons to glutamate caused loss of rhodamine 123 fluorescence and structural damage to mitochondria. Mitochondrial function could be restored and cell survival maintained by addition of glucose prior to the late elevation of [Ca2+]i. Nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor II (IGF-II) prevented loss of both [Ca2+]i homeostasis and mitochondrial transmembrane potential, and protected hippocampal neurons against hypoglycemic injury, but did not prevent the hypoglycemia-induced reduction in ATP levels. NaCN and 2,4 dinitrophenol (DNP) caused a large elevation of [Ca2+]i, mitochondrial dysfunction, and cell death. NGF, bFGF, and IGF-II each significantly reduced the adverse effects of NaCN and DNP on [Ca2+]i, mitochondrial function, and cell survival. Loss of [Ca2+]i homeostasis may be a critical event leading to mitochondrial damage and cell death resulting from energy failure. Preventing loss of [Ca2+]i homeostasis may be a general mechanism for the neuroprotective action of growth factors. PMID- 8495705 TI - An ascending seizure-controlling pathway in the medial brainstem and thalamus. AB - This study demonstrated that an ascending pathway from the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum to the thalamic central medial intralaminar nucleus (CeM) controls the thresholds of experimental seizures. Electrolytic and excitotoxic lesions of the CeM and adjacent thalamus facilitated myoclonic, facial-forelimb clonic, and tonic pentylenetetrazol seizures. Microinjections of the GABAB agonist (-)baclofen in the LDTg facilitated myoclonic and facial-forelimb clonic but not tonic seizures. When LDTg injections of (-)baclofen were performed in animals with prior electrolytic lesions of the midline thalamus, the thresholds of myoclonic and facial-forelimb clonic seizures were unchanged compared to similarly lesioned rats with control vehicle LDTg injections. In addition, the lowering of tonic seizure threshold observed with thalamic lesions was reversed by these (-)baclofen injections. Taken together with past studies, these results imply that the LDTg controls myoclonic and facial-forelimb clonic seizures via ascending projections to the CeM and possibly other medial thalamic nuclei. We also postulate that the LDTg affects tonic seizures by two different, opposing pathways. Although the LDTg-CeM pathway is part of the "ascending reticular activating system," lesions of the midline thalamus did not affect spontaneous sleep, implying that the CeM does not have an essential role in sleep regulation. PMID- 8495706 TI - Inability to detect beta-amyloid protein precursor mRNA in Alzheimer plaque associated microglia. AB - A close association between Alzheimer senile plaques and microglia (the resident mononuclear phagocytic system cells of the brain) is well documented. To determine whether microglia contain detectable beta-amyloid protein precursor (beta-APP) mRNA, the present study combined immunocytochemistry (LN3 antibody to label microglia) with in situ hybridization (full-length cRNA probe to detect all forms of beta-APP mRNA). We report that immunolabeled microglia, including those clustered around senile plaques, generally lack detectable beta-APP mRNA- suggesting that microglia are not synthesizing the plaque-associated amyloid. The possibility that, analogous to the process in other forms of amyloidosis, the resident mononuclear phagocytic cells ingest an amyloidogenic precursor and secrete amyloid was not examined. Recent demonstrations of interactions between immune-related factors and Alzheimer lesions suggest that beta-APP and its breakdown products, along with microglia and their secretory products, may work synergistically in an AD pathogenetic cascade. PMID- 8495707 TI - Excitotoxic injury stimulates glial fibrillary acidic protein mRNA expression in perinatal rat brain. AB - To study the molecular mechanisms contributing to glial fibrillary acidic protein (GFAP) accumulation after neuronal injury in the developing brain, we used a reproducible and pharmacologically modifiable model of excitotoxic injury, intracerebral injection of N-methyl-D-aspartate (NMDA) in Postnatal Day 7 rats. Injection of NMDA into the posterior striatum elicits dose-dependent ipsilateral injury to striatum, hippocampus, and overlying cortex; treatment with the non competitive NMDA antagonist MK-801 is neuroprotective. To examine regionally specific changes in GFAP mRNA expression after lesioning, GFAP mRNA content was assayed, by Northern analysis, in pooled tissue samples of striatum, hippocampus, and cortex, derived from the injected and contralateral hemispheres of animals killed 1-16 days after lesioning with NMDA (12.5 nmol), and in samples derived from lesioned animals and littermates treated with MK-801. In addition, in situ hybridization assays were done to visualize the anatomic distribution of GFAP mRNA expression in NMDA-lesioned (n = 5) and lesioned/MK-801-treated animals (n = 3) 5 days postinjection. There was a marked rise in GFAP mRNA in lesioned cortex within 24 h, and increases were sustained over the next 2 weeks. In contrast, in striatum and hippocampus, in which severe histologic damage evolves, at 24 h postlesioning there was little stimulation of GFAP mRNA expression. Subsequently, 5-16 days postinjury increases in GFAP mRNA were detected in both brain regions. In animals examined 5 days postlesioning, MK-801 treatment markedly attenuated stimulation of GFAP mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495708 TI - Recovery from facial paralysis following crush injury of the facial nerve in hamsters: differential effects of gender and androgen exposure. AB - In recent studies, we have shown that administration of androgens to male hamsters enhances functional recovery from facial paralysis induced by facial nerve crush at the level of the stylomastoid foramen. Furthermore, we have established that the mechanism behind this enhancement of regeneration involves an acceleration of the rate of regeneration, without a shortening in the delay of sprout formation. From those studies, several unexpected findings of inherent sex differences emerged. First, intact (nongonadectomized) females have a faster facial nerve regeneration rate than males and, second, testosterone has a less dramatic effect on the rate of regeneration in females compared to males. In the present study, we explored these novel findings of sex differences in the response of motor neurons to injury. Adult intact female hamsters were subjected to right facial nerve crush axotomy at the level of stylomastoid foramen and either implanted with two or four silastic capsules containing 5 alpha dihydrotestosterone, or sham-implanted for controls. A group of adult intact male hamsters was also subjected to right facial nerve crush axotomy. Animals were observed daily, beginning on Day 1 postoperatively and continuing throughout a 3 week recovery period for signs of functional recovery from facial paralysis. The average day of return of each of four behavioral components (semi-blink, blink reflex, full vibrissae movement, and complete recovery) was calculated for all four experimental groups. The results indicate that intact females recover functional return of movement following crush injury significantly faster than intact males. In contrast to our previous findings in male hamsters, administration of exogenous steroids does not accelerate recovery from facial paralysis in adult female hamsters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495709 TI - Neurotoxic effects of sodium nitroprusside in rat hippocampal slices. AB - To investigate the possible role of nitric oxide (NO) in n-methyl-D-aspartate (NMDA)-induced neurotoxicity we examined the effects of sodium nitroprusside (SNP) in rat hippocampal slices. Incubation with 3 mM SNP for up to 2 h produced neuronal damage characterized by "nuclear ballooning" in CA3 and CA1 pyramidal neurons and interneurons. The nuclear ballooning was not blocked by lowering the external calcium concentration or coincubation with MK-801 and/or 6,7-dinitro quinoxaline-2,3-dione. Two lines of evidence suggest that the SNP neurotoxicity is not mediated by NO. First, inactivation of SNP by UV light failed to prevent the nuclear ballooning. Second, the toxicity was not attenuated by coadministration of hemoglobin. Although cyanide can be released from SNP, potassium cyanide did not mimic the nuclear ballooning. In electrophysiological experiments, 100 microM SNP irreversibly diminished the CA1 population spike amplitude while having less effect on the field excitatory postsynaptic potential. The effect of SNP on population spikes was inhibited by hemoglobin and was not mimicked by light-inactivated SNP. These results suggest that active SNP and light-treated SNP have different effects on hippocampal neurons and that SNP induces damage that differs from that produced by NMDA or cyanide. PMID- 8495710 TI - Unilateral ibotenic acid lesion of the caudate putamen results in D2 receptor alterations on the contralateral side. AB - Dopaminergic projections to the caudate putamen (CPu) involve fibers in the nigrostriatal pathway from the ipsilateral substantia nigra-pars compacta. Post synaptic receptor populations on cells receiving this information are composed of both D1 and D2 dopamine receptor subtypes. In the present study, unilateral lesions of the CPu, with ibotenic acid, caused a significant reduction in D2 receptor mRNA on the ipsilateral side, as evidenced by in situ hybridization. Similarly, a reduction of D2 receptor binding (as demonstrated with [3H]raclopride) was observed on the lesioned side. As expected, there was no significant change in the D2 receptor binding on the contralateral side. However, a significant increase of D2 receptor mRNA (> 100%) was found in the CPu on the contralateral side when compared to sham-lesioned animals. These results indicate that compensatory changes may be occurring on the unlesioned side of the brain. These changes may reflect elevated transcription from DNA to mRNA or decreased translation of the D2 mRNA to protein following unilateral damage in the CPu. The observation of bilateral influence in the striatal dopamine receptor system may be of paramount importance in understanding movement disorders. These findings could influence the interpretation of results obtained in animal models of human disease in which the dopamine receptor system of the basal ganglia is compromised. PMID- 8495711 TI - Mitochondrial impairment reduces the threshold for in vivo NMDA-mediated neuronal death in the striatum. AB - There may be important relationships between glutamate receptor activation and neurotoxicity in neurodegenerative diseases. Previous experiments using cultured neurons have demonstrated a correlation between the metabolic status of neurons and their sensitivity to glutamate receptor-mediated cytotoxicity (Novelli et al. Brain Res. 451, 205, 1988). To examine such a relationship in vivo, we first established a dose-response curve for N-methyl-D-aspartate (NMDA)-induced neuronal death in the rat striatum. We then examined the interaction between metabolic impairment and infusion of NMDA at a dose below the threshold for neurotoxicity. Metabolic impairment was induced by intraperitoneal delivery of 3 nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II (succinic dehydrogenase). Twelve hours after 3-NP delivery we performed stereotactic infusion of NMDA or vehicle into the striatum. During mitochondrial impairment, a relatively nonneurotoxic dose of NMDA (15 nmol) produced a lesion that was significantly larger than that caused by this dose under normal metabolic conditions. At a dose normally below the threshold for neurotoxicity, metabolic impairment significantly increased the likelihood of neuronal death in the striatum by a factor of 5. Lesions were characterized by neuronal loss with gliosis and sparing of traversing fiber bundles. These results demonstrate that metabolic impairment reduces the threshold for glutamate receptor-mediated neurotoxicity in vivo. This potentiation may have implications for understanding the role of "neuronal stress" produced by glutamate receptor activation in neurodegenerative diseases and normal aging. PMID- 8495712 TI - Cellular organization in rat somatosensory cortex: effects of sex and laterality. AB - Layer IV of rodent somatosensory cortex contains distinct arrangements of cells characterized as barrels. When barrels first form in rats, each barrel consists of a cell-dense "wall" and a cell-sparse "hollow." With age, the distinction of the boundary between barrel walls and hollows diminishes. Cellular arrangements within barrels were quantified to test whether the barrels are influenced by sex and laterality during cortical development. A computer-assisted method was developed to measure cell densities in relation to barrel boundaries. The boundaries between barrel walls and hollows were determined in tissue double stained for Nissl substance and cytochrome oxidase histochemistry. The distinction between barrel walls and hollows revealed by Nissl stains differed significantly between anterior and posterior barrels. This distinction declined significantly in anterior barrels from Postnatal Day 10 (P10) to P30. The area of cortex containing barrels was estimated from composites of Nissl-stained sections. At P20 the detectable barrel cortex area was larger on the right in females and on the left in males resulting in a significant sex difference in barrel cortex asymmetry. This sex difference in barrel cortex laterality was detected only in Nissl-stained tissue; there were no differences attributable to sex or side in barrel cortex area analyzed for cytochrome oxidase reactivity. We hypothesize that sex-dependent differences in barrel cortex structure result from lateralized differences in cellular organization. PMID- 8495713 TI - Reestablishment of laminar patterns of cortical acetylcholinesterase activity following axotomy of the medial cholinergic pathway in the adult rat. AB - Little is known about injury-induced restructuring of cholinergic neurons projecting from the basal forebrain to nonhippocampal loci in the mature mammalian brain. In an attempt to address this issue further, we made unilateral knife cuts in the cingulate cortex of adult rats and assessed the rates and extents of fiber regeneration. Among the fibers interdicted by these transections were axons of the medial cholinergic pathway, which originates prominently in the diagonal band nuclei and projects to medial frontal, cingulate, and occipital cortices. Immediately following the lesion, acetylcholinesterase (AChE) containing fibers proximal to the transection demonstrated increased enzyme activity that remained elevated for at least 12 weeks before returning to control values within 9 months. Loss of distal cholinesterase staining was seen from 1-2 weeks postaxotomy, with partial restoration of enzyme activity within 4 weeks. By 12 weeks, virtually complete restitution of laminar patterns of AChE innervation had occurred in the cortex posterior to the knife cut. At least part of this reinnervation was attributable to fibers growing or elongating across the glial scar, with the degree of regrowth being correlated positively with the rapidity and magnitude of wound closure. Sprouting from the cut ends of axons, as well as collateral growth of those and uncut adjacent fibers, are likely sources of fibers contributing to the restoration of normal laminar profiles of AChE activity. PMID- 8495714 TI - Tau proteins are abnormally expressed in olfactory epithelium of Alzheimer patients and developmentally regulated in human fetal spinal cord. AB - In pathological conditions, the microtubule-associated tau proteins may accumulate in neuronal perikarya or be expressed de novo in certain populations of neurons. For example, olfactory epithelium (OE) neurons in Alzheimer's disease (AD) patients express tau in their axons when these axons become dystrophic. In this study, we examined human postmortem olfactory tissue with a panel of tau antibodies that bind to epitopes located in subdomains spanning nearly the entire length of all six known isoforms of human CNS tau. In addition, the developing human spinal cord was probed with a similar panel of tau antibodies to determine whether or not fetal tau epitopes were reexpressed in the dystrophic OE neurites of AD patients. Electron microscopy was performed to examine the ultrastructure of the filaments present in these dystrophic OE neurites. We show here that all the tau epitopes examined are expressed in dystrophic OE neurites of AD patients, but that certain tau epitopes are preferentially expressed in the dystrophic neurites of AD. We also demonstrate that many of the epitopes present in the dystrophic neurites of AD are expressed early in the developing spinal cord and are later extinguished, including adult tau epitopes present in the brain. Finally, our EM studies reveal the presence within dystrophic OE neurites of approximately 10 to 15-nm-diameter filaments. These results suggest that the entire extent of multiple tau molecules is present in dystrophic OE neurites, with certain modifications of tau occurring preferentially in the dystrophic neurites of AD patients. PMID- 8495715 TI - Acetaminophen toxicity in cultured trout liver cells. I. Morphological alterations and effects on cytochrome P450 1A1. AB - To better characterize the hepatotoxicity of acetaminophen, the effects of this drug were investigated on isolated liver cells from a species relatively resistant to acetaminophen toxicity, rainbow trout. At high concentrations of acetaminophen (2-10 mM), pathologic effects were detected, including loss of lactate dehydrogenase from cells, disruption of cell-cell aggregation, cell death, and distinctive alterations in cell morphology, as demonstrated by light and electron microscopic examination. Most striking was the acetaminophen-induced rearrangement of mitochondria, which were clustered adjacent to the nucleus and rarely seen at cell periphery. The endoplasmic reticulum was also altered by acetaminophen treatment. In the middle portion of the cytoplasm, parallel arrays of endoplasmic reticulum cisternae were abundant; however, the peripheral cytoplasm was restricted to vesicular profiles of endoplasmic reticulum. Although nuclei in acetaminophen-treated cells displayed peripheral heterochromatin aggregation, acetaminophen did not produce detectable DNA fragmentation, in contrast to effects reported for mouse liver cells. Thus DNA fragmentation does not appear to be required for acetaminophen to manifest cytotoxic effects. In addition, immunohistochemical studies indicated that toxic concentrations of acetaminophen which altered the endoplasmic reticulum helped maintain cytochrome P450 1A1 in liver cells from beta-naphthoflavone-induced trout. PMID- 8495716 TI - Acetaminophen toxicity in cultured trout liver cells. II. Maintenance of cytochrome P450 1A1. AB - Acetaminophen was demonstrated to maintain cytochrome P450 1A1 (P450 1A1) in isolated rainbow trout liver cells cultured in serum-free medium. This novel finding was characterized in detail. Cultured trout liver cells retained their ability to respond to typical 1A1 inducers in vitro; induction of ethoxyresorufin O-deethylase (EROD) activity was readily demonstrated by exposing liver cells from control trout to beta-naphthoflavone (BNF), Aroclor 1254, or 7,12 dimethylbenz[a]anthracene. BNF was the most potent inducer studied and was used in further experiments. High levels of EROD activity, immunoreactive 1A1, and 1A1 mRNA were expressed in liver cells prepared from trout pretreated with BNF. However, all of these 1A1-specific indicators rapidly declined when cells from BNF-treated trout were placed in culture, and BNF in culture medium was not effective in maintaining EROD activity. Immunohistochemical studies suggested that addition of acetaminophen to liver cells prepared from BNF-induced trout helped maintain elevated levels of P450 1A1. Total cytochrome P450, EROD activity and immunoreactive P450 1A1 were retained in liver cells from BNF-induced trout by the addition of acetaminophen, in a dose-dependent manner. The concentrations of acetaminophen most effective in maintaining P450 1A1 produced cytotoxic effects, including vesiculation of endoplasmic reticulum. Furthermore, the acetaminophen maintenance of P450 1A1 was primarily attributed to elevated levels of P450 1A1 mRNA. In contrast to BNF, acetaminophen was not capable of inducing 1A1 in liver cells prepared from control trout. This is the first report to demonstrate that acetaminophen can help maintain P450 1A1 and that this effect is exerted at the level of P450 1A1 mRNA. PMID- 8495717 TI - Thrombin promotes aortic endothelial cell spreading and microfilament formation in nonconfluent monolayer cultures. AB - Thrombin is present at sites of vascular injury. The objective of this study was to determine if thrombin may regulate endothelial repair. To address this our study was designed to determine the effect of thrombin on cell shape and microfilament distribution of porcine aortic endothelial cells in low-density cultures. Since these cells grow as islands of cells, low-density cultures serve as a model for conditions in which reendothelialization occurs from several foci following prominent patchy endothelial denudation. Thrombin incubation for 1, 2, and 4 hr at 0.5, 4, and 8 U/ml caused a significant increase in both the surface area of endothelial cells and the amount of microfilament bundles occupying the cell surface area. The increase in microfilament bundles was more than would be expected from the increased surface area. However, the pattern of distribution of microfilaments and of vinculin adhesion plaques within the cells was not altered by thrombin. Attempts at understanding the molecular mechanisms involved were undertaken. The role of protein kinase C was studied. Phorbol 12-myristate 13 acetate (PMA) caused cell spreading as well but no increase in microfilaments within the first 2 hr of incubation. Some cells showed mild disruption of microfilaments. Following 24 hr incubation with PMA, which reduces protein kinase C, the cells showed retraction and arborization along with thinning and disruption of microfilaments. Removal of PMA and addition of thrombin reversed these changes to normal within 2 hr while washout of PMA on its own did not alter cell shape or microfilaments. Thrombin also partially reversed the effects of H 7, a protein kinase C inhibitor, which on its own also caused cell retraction and disruption of microfilaments. Neomycin sulfate did not alter the thrombin effect suggesting that the participation of the phosphotidylinositol system is not directly required. In conclusion, thrombin promotes endothelial activities which are associated with long-term endothelial repair; however, these effects do not appear to be directly due to the involvement of conventional isoforms of protein kinase C or the phosphotidylinositol system. PMID- 8495718 TI - Transient morphological and biochemical alterations of arterial proteoglycan during early wound healing. AB - Proteoglycan alterations in the carotid arteries of normolipemic rabbits during the first 14 days after injury were evaluated by morphometric analysis of ruthenium red-stained sections using transmission electron microscopy and by incorporation of 35S-sulfate. Two types of de-endothelializing injury were compared, air-drying and balloon catheter. Three days after either injury, a transient increase in concentration of 35S-labeled glycosaminoglycans, changes in distribution of 35S-sulfate among glycosaminoglycans, and a two- to threefold increase in 35S-sulfate content (measured as 35S/micrograms glycosaminoglycan) were observed. Morphometric analysis revealed an alteration in medial proteoglycan distribution and morphology at 3 days after injury, which was more evident after air-drying than balloon injury. In response to either injury, metabolically activated smooth muscle cells were associated with very large proteoglycan granules (diameter: > 60 nm) which possibly contained glycosaminoglycans with longer chains and/or altered charge densities. By 14 days after either injury, the distribution of medial proteoglycan returned to normal and a neointima formed. The neointima was thicker following balloon injury, but irrespective of the nature of the injury proteoglycan concentration was higher in the re-endothelialized than in non-reendothelialized areas. The alterations in extracellular proteoglycan of the intima-medial layers induced by these two forms of injury may influence the pattern of wound healing but are not associated with lipid deposition within the time frame examined. PMID- 8495719 TI - New model for 70 kDa heat-shock proteins' potential mechanisms of function. AB - The 70 kDa family of heat-shock proteins (hsp 70s and hsc 70s) can facilitate protein transport to several organelles. This process is thought to involve electrostatic interactions between hsp 70s and the cellular protein targeting sequences. Analysis of the highly conserved structural and functional properties of the hsp 70 family indicated that they may cross-link cellular proteins to the actin microfilament network. Direct experimental support for this hypothesis was provided by the finding that hsp 70 is constitutively bound to actin through hydrophobic interactions. The cross-linker model may provide an explanation for the mechanism by which the cytoskeletal matrix could mediate various cellular processes. PMID- 8495720 TI - WWamide-1, -2 and -3: novel neuromodulatory peptides isolated from ganglia of the African giant snail, Achatina fulica. AB - Three novel neuropeptides, isolated from ganglia of the African giant snail, Achatina fulica, were named WWamide-1, -2 and -3. These substances were biologically active heptapeptide amides with a Trp residue at both the N- and C termini. WWamide-1, which displayed an inhibitory activity on a central neuron of the snail, exhibited peripherally modulatory effects on muscular contractions of not only the gut and other tissues of the snail but also certain tissues of other molluscs. PMID- 8495721 TI - Thyroid hormones promote transcriptional activation of the nuclear gene coding for mitochondrial beta-F1-ATPase in rat liver. AB - Thyroid hormones acutely regulate gene expression of the beta-catalytic subunit of the mitochondrial F1-ATPase complex in the liver of hypothyroid rat neonates at either a transcriptional and/or post-transcriptional level [(1990) J. Biol. Chem. 265, 9090-9097]. Administration at birth of various thyroid hormone doses to hypothyroid newborn rats promote a rapid (1 h) increase in liver steady-state amounts of both beta-F1-ATPase protein and mRNA. Induction of the beta-F1-ATPase mRNA is coincident with an elevation in gene transcription detected using nascent RNA chains synthesized by isolated nuclei. These results suggest that thyroid hormones induction of postnatal mitochondrial differentiation in the liver of hypothyroid rat neonates is mostly triggered by transcriptional regulation of beta-F1-ATPase gene. PMID- 8495722 TI - Inositol 1,4,5-trisphosphate releases Ca2+ from vacuolar membrane vesicles of Saccharomyces cerevisiae. AB - Inositol 1,4,5-trisphosphate (IP3) induces a release of Ca2+ from vacuolar membrane vesicles of Saccharomyces cerevisiae. The amount released is dependent on IP3 concentration (concentration for half maximal effect, Km, apparent = 0.4 microM). Myo-inositol, and inositol 1,4-bisphosphate up to 50 microM have no effect on Ca2+ levels in the vesicles. The IP3-induced Ca2+ release is blocked by dantrolene and 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate-HCl (TMB-8), which are known to block Ca2+ release from Ca2+ stores in animal cells. IP3 induced release of Ca2+ also occurs when Ca2+ is accumulated by means of an artificial pH gradient, indicating that the effect of IP3 is not due to an effect on the vacuolar H(+)-ATPase. The IP3-induced Ca2+ release is not accompanied by a change in the pH gradient, which indicates that it is not due to a reversal of the Ca2+/nH+ antiport or to a decrease in delta pH by IP3. The present results suggest that IP3 may act as a second messenger in the mobilization of Ca2+ in yeast cells. As in plant cells, the vacuolar membrane of yeast seems to contain a Ca2+ channel, which can be opened by IP3. In this respect the vacuole could function as an IP3-regulated intracellular Ca2+ store, equivalent to the endoplasmic- and sarcoplasmic reticulum in animal cells, and play a role in Ca(2+)-dependent signal transduction in yeast cells. PMID- 8495723 TI - Purification and molecular cloning of chymase from human tonsils. AB - A chymotrypsin-like protease was purified to homogeneity from human tonsils by a series of chromatographic procedures. The purified enzyme gave a single protein band with an apparent molecular mass of 30 kDa on SDS-PAGE. The sequence of the first 21 amino acids at the N-terminus of the enzyme was determined. A cDNA for the enzyme was cloned by PCR amplification from extracted tonsillar mRNA using a supposed N-terminal oligonucleotide primer and a conserved C-terminal primer of the chymase family. The deduced amino acid sequence of the isolated clone was identical to that of human chymase in connective tissue-type mast cells from heart except for a Ser instead of a Cys at the N-terminal 7th position. PMID- 8495724 TI - Glibenclamide and meglitinide block the transport of low molecular weight solutes into malaria-infected erythrocytes. AB - Following infection by the malaria parasite, human erythrocytes show increased uptake of a wide variety of low molecular weight solutes via pathways with functional characteristics different from those of the transporters of normal erythrocytes. In this study glibenclamide and meglitinide were shown to inhibit the induced transport of a sugar alcohol (sorbitol), an amino acid (threonine), an inorganic anion (Cl-) and an organic cation (choline) into human erythrocytes infected in vitro with Plasmodium falciparum. The results are consistent with the hypothesis that a diverse range of substrates enter malaria-infected cells via common pathways which have features in common with Cl- channels in other cell types. glibenclamide and meglitinide were also shown to inhibit the in vitro growth of the intracellular parasite which would suggest that these pathways may be a viable chemotherapeutic target. PMID- 8495725 TI - Processing of Kex2 pro-region at two interchangeable cleavage sites. AB - In Saccharomyces cerevisiae, the Kex2 endoprotease (Kex2p) is required for the proteolytic maturation of alpha-pheromone and also for the removal of its own pro region. Kex2p is specific for pairs of basic amino acid residues. Two putative processing sites are present in the pro-region of Kex2p. We have expressed processing site mutants of Kex2p and assayed the production of active Kex2p. Mutations affecting either putative cleavage site do not alter the activity. However, mutations affecting both sites led to a reduction in both Kex2 activity and the amount of protein. These results suggest that removal of Kex2p pro peptide is required for the production of a stable enzyme and can occur at either processing site. PMID- 8495726 TI - A bacterial enzyme degrading the model lignin compound beta-etherase is a member of the glutathione-S-transferase superfamily. AB - Cleavage of beta-aryl ether linkages is essential in lignin degradation. We identified another beta-etherase gene (ligF), which contains an open reading frame of 771 bp and lies between genes coding C alpha-dehydrogenase (ligD) and beta-etherase (ligE). The beta-etherase activity of LigF expressed in Escherichia coli was more than 80 times as high as that of LigE. ligF and ligE are homologous to glutathione-S-transferase, and upon addition of glutathione a remarkable acceleration of beta-etherase activity was found in E. coli carrying ligF. It is concluded that LigF plays a central role in beta-aryl ether cleavage and that glutathione is the hydrogen donor in this reaction. PMID- 8495727 TI - 8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo. AB - An adenosine antagonist, 8-(3-chlorostyryl)caffeine (CSC), was shown previously to be 520-fold selective for A2a-adenosine receptors in radioligand binding assays in the rat brain. In reversing agonist effects on adenylate cyclase, CSC was 22-fold selective for A2a receptors in rat phenochromocytoma cells (Kb 60 nM) vs. A1 receptors in rat adipocytes (Kb 1.3 microM). Administered i.p. in NIH mice at a dose of 1 mg/kg, CSC shifted the curve for locomotor depression elicited by the A2a-selective agonist APEC to the right (ED50 value for APEC shifted from 20 micrograms/kg i.p. to 190 micrograms/kg). CSC had no effect on locomotor depression elicited by an ED50 dose of the A1-selective agonist CHA. CSC alone at a dose of 5 mg/kg stimulated locomotor activity by 22% over control values. Coadministration of CSC and the A1-selective antagonist CPX, both at non stimulatory doses, increased activity by 37% (P < 0.001) over CSC alone, suggesting a behavioral synergism of A1- and A2-antagonist effects in the CNS. PMID- 8495728 TI - Orientation and nearest neighbor analysis of psbI gene product in the photosystem II reaction center complex using bifunctional cross-linkers. AB - Two distinct cross-linked products containing psbI gene product were generated in the photosystem II reaction center complex from spinach by treatment with bifunctional reagents directed to amino groups. The first product, which was generated by a 3,3'-dithiobis(succinimidyl propionate) treatment, is deduced to be formed between the epsilon-amino group of Lys3 of the psbI gene product, and a side-chain amino group present on the stromal extension of the D2 protein. The CNBr cleavage analysis of the cross-linked product predicted that the amino group of the D2 protein engaged in the cross-linking is either one of the three lysine residues on the N-terminal fragment (from N-terminus to Met19) or the Lys268 on the 6th fragment (from Val248 to Met275). The second product, which was also generated on the stromal side by a 1,6-hexamethylene diisocyanate treatment preferentially in alkaline conditions, is predicted to be formed between the epsilon-amino group of Lys3 of the psbI gene product and the N-terminal alpha amino group of the alpha-subunit of cytochrome b559. PMID- 8495729 TI - Cell-penetrating inhibitors of calpain block both membrane fusion and filamin cleavage in chick embryonic myoblasts. AB - Benzyloxycarbonyl(Z)-Leu-nLeu-H (calpeptin) and Z-Leu-Met-H, cell-penetrating inhibitors of calpain, were found to block myoblast fusion without any effect on cell proliferation and alignment along their bipolar axis. They also inhibited the accumulation of creatine kinase during myogenesis. These effects were dose dependent, and could be reversed upon removal of the drug from the culture medium. Furthermore, treatment of the inhibitors prevented the hydrolysis of filamin, which is sensitive to cleavage by calpain in vitro and interferes with actin-myosin filament formation by cross-linking F-actin molecules. On the other hand, leupeptin, which can also inhibit calpain in vitro but can not penetrate into cells, showed little or no effect on both myoblast fusion and filamin clevage. These results suggest that calpain may play an important role in cytoskeletal reorganization that is requisite for myoblast fusion. The role of calpain on the expression of muscle-specific proteins remains unknown. PMID- 8495730 TI - Glycosaminoglycans exposed on the endothelial cell surface. Binding of heparin like molecules derived from serum. AB - We have analyzed the glycosaminoglycans exposed on the surface of endothelial cells cultured in vitro. The cells were labelled with [35S]sodium sulfate. Chondroitin sulfate, heparan sulfate and dermatan sulfate are the main sulfated glycosaminoglycans present on the cell surface. They are synthesized by endothelial cells. However, the electrophoretic analysis and corresponding autoradiography of the glycosaminoglycans removed from the endothelial cell surface shows the presence of heparin-like compound which is not synthesized by the cells as it is unlabelled by [35S]sodium sulfate. We show here that a proteolytic treatment of the commonly used serum for cell culturing, reveals the presence of an heparin-like anticoagulant activity. These results suggest that the endothelial cells bind endogenous heparin-like molecules present in serum. PMID- 8495731 TI - Spectral hole burning study of intact cells of green bacterium Chlorobium limicola. AB - Spectral hole burning studies of intact cells of the green bacterium, Chlorobium limicola, have proven that the Qy-absorption system of antenna bacteriochlorophyll c (BChl c) should be interpreted in terms of the delocalized exciton level structure of an oligomer. For the first time the 0-0 band of the lowest exciton state of BChl c oligomers has been directly detected as the lowest energy inhomogeneously broadened band (FWHM approximately 100 cm-1; position of maximum, at approximately 774 nm) of the near-infrared BChl c band of 1.8K excitation spectrum (FWHM = 830 cm-1; position of maximum, at 751 nm). PMID- 8495732 TI - Direct influence of morphine on the release of arachidonic acid and its metabolites. AB - The influence of 10(-10)-10(-6) M morphine on the release of [3H]arachidonic acid and its metabolites ([3H]AAM) from prelabeled resident peritoneal murine macrophages was investigated. Morphine enhanced [3H]AAM release from A23187- and LPS-stimulated macrophages, as well as the basal release of [3H]AAM. Dose response curves showed a maximum at 10(-8) M morphine. Naloxone had no effect on morphine enhancement of [3H]AAM release. These results are in agreement with the hypothesis that [3H]AAM may be involved in the effects of morphine. PMID- 8495733 TI - Inactivation of alpha-ketoglutarate dehydrogenase during oxidative decarboxylation of alpha-ketoadipic acid. AB - alpha-Ketoglutarate dehydrogenase was inactivated irreversibly and completely during oxidation of alpha-ketoadipic acid. The inactivation was revealed both in the model system with ferricyanide and in the overall reaction catalyzed by the alpha-ketoglutarate dehydrogenase complex. Neither substrate depletion nor product accumulation induced the inactivation. The results obtained were compared with recent data on the enzyme inactivation during oxidation of alpha ketoglutaric acid. The differences in the inactivation kinetics observed with the two substrates of the enzyme were analyzed. They seem not to reflect the different mechanisms of the inactivation, but, rather, depend on the changes in the rates of the individual stages of the process. PMID- 8495734 TI - Participation of tyrosine kinase in capping, internalization, and antigen presentation through membrane immunoglobulin in BAL17 B lymphoma cells. AB - BAL17 cells pulsed with goat anti-IgM or anti-IgD as antigens stimulated a goat IgG specific T cell clone in terms of inositol phosphate production. The antigen presenting capacity of BAL17 cells was inhibited by pretreatment with the tyrosine kinase inhibitors herbimycin A or genistein. Furthermore, ligand-induced capping and endocytosis of membrane immunoglobulin, monitored at the single cell level, was also blocked by herbimycin A. These results indicate that tyrosine phosphorylation plays an important role in receptor-mediated antigen presentation by B cells. PMID- 8495735 TI - Random-splitting of tRNA transcripts as an approach for studying tRNA-protein interactions. AB - Location of phosphodiester bonds essential for aminoacylation of bovine tRNA(Trp) was identified using a randomly cleaved transcript synthesized in vitro. It was found that cleavage of phosphodiester bonds after nucleotides in positions 21, 22, 36-38, 57-59, 62 and 64 were critical for aminoacylation capacity of tRNA(Trp)-transcript. These cleavage sites were located in the regions of tRNA molecule protected by the cognate synthetase against chemical modification and in the regions presumably outside the contact area as well. These results indicate that for maintenance of aminoacylation ability the intactness of the certain regions of the tRNA backbone structure is necessary. Random splitting of non modified RNA with alkali followed by separation of active and inactive molecules and identification of cleavage sites developed in this work may become a general approach for studying the role of RNA covalent structure in its interaction with proteins. PMID- 8495736 TI - A benzopyrylium dye as a novel effective cationic uncoupler of oxidative phosphorylation. AB - Benzopyrylium dye BDBP was found to be an effective uncoupler of oxidative phosphorylation. It stimulates state 4 respiration of mitochondria 2-fold at about 2 microM, reveals a maximum stimulation (8-fold) at 30 microM and inhibits the respiration at higher concentrations. BDBP is also an effective proton (hydroxyl) carrier through bilayer lipid membranes (BLM) as is seen from the electrical properties of BLM with BDBP. Picrate enhances the effects of BDBP on the mitochondrial respiration and BLM conductance. The BDBP activities are accounted for by formation of dimers and complexes with picrate. PMID- 8495737 TI - The GP-protein of Marburg virus contains the region similar to the 'immunosuppressive domain' of oncogenic retrovirus P15E proteins. AB - cDNA was synthesized and cloned on the template of the genomic RNA of Marburg virus (strain Popp). Recombinant plasmids with specific cDNA inserts were selected and sequenced. The length of the open reading frame encoding the GP protein is 681 amino acids. GP-protein is proposed to be an integral membrane protein. Computer-assisted comparison of the deduced amino acid sequence with those of different viruses revealed significant homology with the GP-protein of Ebola virus and with the 'immunosuppressive domain' of the P15E envelope proteins of some oncogenic retroviruses. PMID- 8495738 TI - Mitochondrial oxidative phosphorylation in saponin-skinned human muscle fibers is stimulated by caffeine. AB - The addition of 15 mM caffeine to saponin-skinned human muscle fibers from M. vastus lateralis caused in the presence of 2 mM ATP an approx. 2-fold stimulation of respiration with glutamate+malate. This effect can be abolished by either the addition of the Ca2+ chelator EGTA, the inhibitor of Ca2+ transport Ruthenium red and the inhibitor of the myosin ATPase vanadate. The caffeine concentration dependency of respiration of fibers coincided with the caffeine-caused stimulation of myosin ATPase activity. The activation of oxidative phosphorylation in saponin-skinned human muscle fibers by caffeine can be explained by a stimulation of myosin ATPase caused by Ca2+ release from sarcoplasmic reticulum. PMID- 8495739 TI - Kinetics and energetics of redox regulation of ATP synthase from chloroplasts. AB - The rate of ATP hydrolysis catalyzed by the membrane-bound CF0F1 ATP synthase from chloroplasts served as a probe for the determination of the reduction grade of the enzyme treated with dithiothreitol (DTT) or thioredoxin. Rate constants for reduction were obtained. It turns out that reduction by thioredoxin is about a factor of 6,000 more effective than DTT reduction. The activation profiles with respect to delta pH were obtained for reduced and oxidized ATPases. The activation curve of reduced enzyme turns out to have its half-maximum degree of activation at delta pH = 1.65, which is considerably lower than reported hitherto. The corresponding value of the oxidized enzyme has been obtained from the rate of ATP hydrolysis in the case of incomplete reduced ATPases, taking into account the aforementioned rate constants, and comes to delta pH = 3.35. PMID- 8495740 TI - Enhancement of phospholipase A2 activation by phosphatidic acid endogenously formed through phospholipase D action in rat peritoneal mast cell. AB - Contribution of phosphatidic acid (PA) generated by activated phospholipase (PL) D to PLA2 activation was studied in rat peritoneal mast cells. Exogenous didecanoyl PA induced arachidonate liberation in the permeabilized cells which was inhibited by p-bromophenacyl bromide. Upon exposure of the cells to ethanol in a high enough concentration to prevent PA formation, A23187-induced arachidonate liberation was suppressed by 50% and the rest was completely inhibited by p-bromophenacyl bromide. In contrast, propranolol, which enhanced PA accumulation, significantly increased the arachidonate liberation. These results suggest that A23187-induced PLA2 activation may be potentiated, at least in part, by PA generated through PLD action. PMID- 8495741 TI - Increased expression of F1ATP synthase subunits in yeast strains carrying point mutations which destabilize the beta subunit. AB - In yeast strains (S. cerevisiae) carrying a point mutation of the ATP2 gene, which destabilizes the beta subunit of F1 ATP synthase in vitro, the growth rate was reduced significantly, demonstrating that the mutation is also deleterious in vivo. Immunoblots showed that levels of the mutated beta, but also of the wild type alpha subunit were increased in the mutated strains, together with levels of the corresponding mRNAs (approximately 1.6-fold). Northern analysis showed that this was due to both the appearance of new transcript species as well as upregulation of the cognate transcripts, strongly indicating that the increase was probably due to activation of transcription. Levels of other mitochondrial proteins, e.g. cytochrome c oxidase, were unaffected. We conclude that a specific signal communicates the actual performance of the ATP synthase inside the mitochondria to the nuclear genes encoding its subunits. PMID- 8495742 TI - Derivation of the formyl-group oxygen of chlorophyll b from molecular oxygen in greening leaves of a higher plant (Zea mays). AB - Using mass spectroscopy, we demonstrate as much as 93% enrichment of the 7-formyl group oxygen of chlorophyll b when dark-grown, etiolated maize leaves are greened under white light in the presence of 18O2. This suggests that a mono-oxygenase is involved in the oxidation of its methyl group precursor. The concomitant enrichment of about 75% of the 13(1)-oxygen confirms the well-documented finding that this oxo group, in both chlorophyll a and b, also arises from O2. High 18O enrichment into the 7-formyl oxygen relative to the substrate 18O2 was achieved by optimization of the greening conditions in combination with a reductive extraction procedure. It indicates not only a single pathway for Chl b formyl group formation, but also unequivocally demonstrates that molecular oxygen is the sole precursor of the 7-formyl oxygen. PMID- 8495743 TI - Identification of the psbH gene product as a 6 kDa phosphoprotein in the cyanobacterium Synechocystis 6803. AB - The product of the psbH gene has been identified in Synechocystis 6803 thylakoid membranes as a 6 kDa phosphoprotein. This protein becomes phosphorylated in vitro despite the fact that in cyanobacteria it is truncated at the N-terminus such that the phosphorylation site identified in the higher plant protein is missing. Phosphorylation occurred both in the light and in the dark but was inhibited by oxidising conditions, DCMU and zinc ions. The cyanobacterial 6 kDa phosphoprotein degrades when the membranes are subjected to high intensity illumination. PMID- 8495744 TI - Liver-enriched HNF-3 alpha and ubiquitous factors interact with the human transferrin gene enhancer. AB - The human transferrin gene enhancer is organized in two domains. Domain A contains a single enhanson designated Ia. Domain B contains four enhansons named Ib, II, III and IV. We demonstrate here that the liver-enriched transcription factor HNF-3 alpha interacts with enhanson Ia and that enhansons Ib and IV are binding sites for members of the NF1 family. In addition, enhansons II and III seem to be respectively the targets for the AP4 protein and for EIII, a factor not yet completely identified. Analysis of mutated enhancer regions establishes that each enhanson is required for full enhancer activity and that the proteins binding to enhansons II, III and IV may interact within a multiprotein complex. This enhancer region presents no activity in the Sertoli cells of testis, where transferrin is also synthesized. We demonstrate that in Sertoli cells, the members of the HNF-3 family are not expressed; this fact may account for the inactivity of the enhancer in these cells. PMID- 8495745 TI - Human islet amyloid polypeptide transgenic mice as a model of non-insulin dependent diabetes mellitus (NIDDM). AB - To model islet amyloidogenesis in NIDDM and explore the glucoregulatory role of islet amyloid polypeptide (IAPP), we have created transgenic mice containing a rat insulin-I promoter-human IAPP fusion gene. Expression of human IAPP was localized to the islets of Langerhans, anterior pituitary and brain in transgenic animals; blood IAPP levels were elevated 5-fold while fasting glucose levels remained normal. Amyloid deposits have not been detected in transgenic islets suggesting that other co-existing abnormalities in NIDDM may be required for the formation of islet amyloid. These animals provide a unique model for exploring this hypothesis and other proposed functions of IAPP. PMID- 8495746 TI - Immunocytochemical analyses of annexin V (CaBP33) in a human-derived glioma cell line. Expression of annexin V depends on cellular growth state. AB - The subcellular distribution of annexin V, a calcium-dependent phospholipid- and membrane-binding protein, in a human-derived cell line, GL15, was investigated by immunocytochemistry at light and electron microscope levels. Annexin V was found diffusely in the cytoplasm and associated with plasma membranes, membranes delimiting cytoplasmic vacuoles, membranes of the endoplasmic reticulum, and filamentous structures the identity of which remains to be established. By immunocytochemistry at the light microscope level and immunochemistry, the expression of annexin V in these cells was found to depend on cellular growth stage, being maximal soon after plating and progressively declining thereafter. However, re-expression of annexin V was observed whenever cell proliferation slowed down or arrested. These findings suggest that annexin V in glioma cells is mostly expressed in connection with cell differentiation. Also, the present ultrastructural data suggest that plasma membranes, membranes of the endoplasmic reticulum and the cytoskeleton are prominent sites of action of annexin V in vivo, thus lending support to the possibility that this protein might have a role in the regulation of cytoskeleton elements and/or of the structural organization of membranes. PMID- 8495747 TI - Occurrence and sequence of a DnaJ protein in plant (Allium porrum) epidermal cells. AB - Antibodies raised against a purified fraction from microsomal membranes of leek epidermal cells were used to screen a lambda zap expression library from epidermal cells of leak plants. A near full-length clone was isolated. This cDNA contains an open reading-frame of 1,191 bp coding for a DnaJ protein (leek DNAJ 1 or LDJ1). Leek DnaJ1 represents the second protein of this type described in a pluricellular organism, the first being that sequenced from human cells. PMID- 8495748 TI - Detection of minor adducts in cisplatin-modified DNA by transcription footprinting. AB - Two DNA restriction fragments containing either a d(GC)5 or a d(TTGCTTGATTAGTTGTGTT) insert were subjected to reaction with cis diamminedichloroplatinum(II) and were then used as templates for RNA synthesis by T7 RNA polymerase. Within the d(GC)5 insert, interstrand cross-links are preferentially formed. Within the second insert, the reactivity order of the potential binding sites is d(ApG) > d(GpC/GpC) = d(GpA) > d(GpTpG). In the presence of cyanide ions, the adducts are much less stable at the d(GpA) sites than at the d(GpCpG) sites, in double-stranded DNA. PMID- 8495749 TI - Chemical crosslinking with disuccinimidyl tartrate defines the relative positions of the two antiparallel coiled coils of the desmin protofilament unit. AB - Filaments formed by desmin, the myogenic intermediate filament protein, were crosslinked with the lysine specific crosslinker DST (disuccinimidyl tartrate; 0.64 nm span) and three DST crosslinked peptides were characterized. Two correspond to crosslinks previously obtained with the longer crosslinker EGS (ethylene glycol bis(succinimidylsuccinate), 1.61 nm span) which defined the antiparallel on-stagger relationship of neighbouring coiled coils. The two DST crosslinks now provide the relative positions of the coiled coils within a limit of about 9 alpha-helical residues. The third DST crosslink most likely connecting two helices of a single coiled coil gives a direct measure of the distance spanned in DST crosslinks. PMID- 8495750 TI - Three-dimensional structure and antigenicity of transmembrane-protein peptides of the human immunodeficiency virus type 1. Effects of a neutralization-escape substitution. AB - A point mutation (Ala-589 to Thr) in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to decrease the sensitivity of the virus to the neutralizing effect of human HIV-1 specific antibodies [(1990) J. Virol. 64, 3240-3248]. Here 17-residue peptides with the parental and mutant sequences were compared: the parental peptide bound antibodies of sera from HIV-1 infected persons more frequently and with higher affinity than the mutant peptide. However, according to circular dichroism (CD), NMR spectroscopy and molecular modelling the peptides have indistinguishable backbone conformations under a variety of experimental conditions. These techniques showed for both peptides that no ordered helix was present in water solution. However, for both peptides in alcohol-water solutions approximately 60% alpha-helix could be induced. The three-dimensional structures of these peptides provide a basis for understanding how this mutation in the transmembrane protein may affect the interaction with both the outer envelope glycoprotein and with antibodies. PMID- 8495751 TI - Wound-induced systemic accumulation of a transcript coding for a Bowman-Birk trypsin inhibitor-related protein in maize (Zea mays L.) seedlings. AB - The wound-induced accumulation of a transcript coding for a polypeptide of 72 amino acid residues in maize (Zea mays L.) seedlings was investigated. Sequence comparison showed strong homology with Bowman-Birk trypsin inhibitors of cereal and legume species. The local accumulation pattern of this transcript demonstrated, after wounding various parts of the seedling, a local as well as a systemic response which implies the transmission of a wound signal specifically from the lower to the upper parts of the plant. PMID- 8495752 TI - E. coli expression and characterization of a mutant troponin I with the three cysteine residues substituted. AB - A TnI cDNA was cloned from rabbit fast skeletal muscle, and site-directed mutagenesis was applied to replace all the three cysteine residues, Cys-48 and Cys-64 by Ala and Cys-133 by Ser. The mutant and wild-type TnI were expressed in E. coli and purified to homogeneity. No significant functional differences were observed between the mutant and the authentic TnI in terms of the interactions with TnT and TnC, and the ability of the reassembled Tn complex to regulate the acto-S1 ATPase activity in a calcium-dependent manner. These findings suggest that none of the cysteine residues in TnI are essential for the function of this protein and can be replaced to obtain a non-oxidizable mutant TnI which is much easier to handle and suitable as an alternative to the authentic TnI for various purposes, such as crystallization of TnI and the whole Tn, and 1H NMR studies. PMID- 8495753 TI - Vitamin D binding protein is produced by human monocytes. AB - The expression of the DBP (vitamin D binding protein) gene was investigated in monocytes and in peripheral blood lymphocytes. DBP message was amplified through 35 cycles of PCR amplification using specific oligonucleotide primers. PCR products of the expected size were further identified by Southern blotting using a specific DBP probe. No expression of the DBP gene could be detected in peripheral blood lymphocytes, nor in the monocyte-derived U 937 cell line. In contrast, message for DBP was identified in monocytes activated with lipopolysaccharide when analyzed between 6 and 10 h following stimulation. These results suggest that the temporal expression of the DBP gene could play a major role in the activation of monocytes by 1-25(OH)2D3. PMID- 8495754 TI - High level expression of the large subunit of mouse ribonucleotide reductase in a baculovirus system. AB - The large subunit of ribonucleotide reductase from mouse has been overexpressed in Spodoptera frugiperda cells infected with recombinant baculovirus. The expressed protein was purified by affinity chromatography to apparent homogeneity as determined by SDS-PAGE. The homogeneous protein is recognized in Western blot analysis by a monoclonal antibody raised to the large subunit of ribonucleotide reductase from calf thymus, has the correct N-terminal sequence, and, in the presence of the small subunit of mouse ribonucleotide reductase and nucleoside triphosphate effectors, catalyzes the reduction of both purine and pyrimidine nucleoside diphosphates. PMID- 8495755 TI - A sialic acid analogue acting as a receptor determinant for binding but not for infection by influenza C virus. AB - We describe a synthetic sialic acid analogue, 9-thioacetamido-N-acetylneuraminic acid (9-thioacetamido-Neu5Ac), which is recognized by the receptor-binding activity of influenza C virus, but is resistant to the receptor-destroying enzyme (acetylesterase) of this virus. Following transfer of the analogue to the surface of receptor-negative cells, influenza C virus is able to attach to these cells, but is unable to infect the cells. This result suggests that inactivation of virus receptors by the receptor-destroying enzyme is essential for initiation of infection. Because of their unique properties such analogues promise to be powerful chemotherapeutic agents. PMID- 8495756 TI - Enrichment of proteinase activity in deteriosomes, a new class of microvesicles. AB - Non-sedimentable microvesicles, termed deteriosomes, have been isolated from the cytosol of bean cotyledons by ultrafiltration, and found to be enzymatically active. Specifically, they possess proteinase activity that is able to catabolize exogenous proteins as well as deteriosome proteins. The proteolytic activity is inhibited by heat-denaturation and known proteinase inhibitors (iodoacetate and phenylmethylsulfonyl fluoride), and the pattern of deteriosome-associated proteinase activity changes with advancing senescence of the cotyledon tissue. Deteriosomes are formed by blebbing from membranes. The finding that they possess proteinase activity is consistent with an earlier proposal [(1991) Proc. Natl. Acad. Sci. USA 88, 2269-2273] that they are involved in membrane turnover and serve as a vehicle for moving bilayer-destabilizing phospholipid and protein catabolites out of membranes into the cytosol for further processing. The data also indicate that a significant proportion of the proteinase activity traditionally considered to be cytosolic is associated with deteriosomes. PMID- 8495757 TI - Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase. AB - OBJECTIVE: To review studies that have examined the role of LH, its mechanism of action, and its detrimental effects when hypersecreted during the follicular phase. DESIGN: Important published studies related to this topic were identified through a computerized bibliographic search. PATIENTS, PARTICIPANTS: Review of the need for LH during the follicular phase is based on animal models and women with hypogonadotropic hypogonadism. The association of hypersecretion of LH during the follicular phase with low rates of fertilization and high rates of pregnancy loss is based on clinical studies conducted in patients treated by IVF and ET and by induction of ovulation. The possible mechanism by which the effects occur is based on in vitro studies. RESULTS: The results of the studies cited in this review are consistent with the two-cell two-gonadotropin hypothesis implying that synergistic action of both FSH and LH is required for appropriate steroidogenesis. It also seems that, whatever the underlying mechanism, a raised serum LH concentration during the follicular phase confers a substantial risk of infertility and early pregnancy loss. CONCLUSION: By reviewing the literature it appears that LH exhibits an important role in the development of the growing follicle and maturation of the oocyte. It also seems that hypersecretion of LH during the follicular phase implies adverse effects on the fertility process. To further test this hypothesis, we now need systemic assessment of the methods of therapy used for treating patients with polycystic ovary syndrome, in relation to LH secretion and outcome of pregnancy. PMID- 8495758 TI - Why should the American Fertility Society be represented at the American Medical Association? PMID- 8495759 TI - Pregnancy after metroplasty for uterine anomalies. AB - OBJECTIVE: To clarify the relation between metroplasty for correction of uterine anomalies and subsequent pregnancy, we reviewed the charts of all patients for whom a diagnosis of bicornuate, septate, or didelphic uterus had been made between 1972 and 1982 and analyzed their obstetric outcomes. DESIGN: Of the 146 patients evaluated, 23 received a metroplasty procedure, and 123 patients did not have surgical intervention. Fifteen of the nonsurgical patients could be matched with 15 of the surgical patients by age, chief complaint, gravidity, and type of anomaly and therefore served as matched controls. RESULTS: The percentage of patients with living children after the diagnosis of uterine anomaly was 67% for the matched nonsurgical group and 73% for the patients who underwent metroplasty. The difference was not statistically significant. Although marked improvement in fetal salvage rates was noted when reproductive outcomes before and after metroplasty were compared, the obstetric outcome was similar to that of the control groups after the diagnosis was made and surgery deferred. CONCLUSION: The efficacy of metroplasty in the treatment of multiple pregnancy losses is thus being questioned. PMID- 8495760 TI - Correlation between fetal heart rate, crown-rump length, and beta-human chorionic gonadotropin levels during the first trimester of well-timed conceptions resulting from infertility treatment. AB - OBJECTIVES: To evaluate sequential changes in fetal heart rate (FHR) during the first trimester of well-timed pregnancies resulting from infertility treatment and to correlate the data with fetal growth curve and beta-hCG levels. DESIGN: Serial measurements of FHR, crown-rump length (CRL) and beta-hCG at weekly intervals throughout the first trimester in 67 consecutive conceptions, resulting from infertility treatment. The day of preovulatory LH surge or of exogenous hCG administration was known in each case. SETTING: Hospital based and private assisted reproductive technology centers. RESULTS: Mean FHR was 108 +/- 12, 26 to 30 days after LH/hCG (5 weeks, 4 days from last menstrual period [LMP]) in embryos 3 +/- 0.3 mm in size; the FHR gradually increased, reaching a peak of 177 +/- 10 on days 51 to 55 (9 weeks from LMP) in embryos of 23 +/- 5.5 mm; it decreased to 156 +/- 5 on days 76 to 80 (12 weeks, 5 days from LMP) in embryos of 62 +/- 5.7 mm. There was, previously not reported, high level correlation between beta-hCG and FHR during the entire first trimester and positive correlation between FHR and CRL during the first 55 days from conception. CONCLUSIONS: During the first trimester of pregnancy, FHR closely follows beta-hCG pattern. Correlation between beta-hCG and FHR is an interesting phenomenon that needs further investigation. PMID- 8495761 TI - The prognostic value of serum concentrations of progesterone, estradiol, and luteinizing hormone during superovulation with and without adjunctive leuprolide therapy. AB - OBJECTIVE: To determine the predictive value of preovulatory serum concentrations of P, E2, and LH for pregnancy achieved with IUI after superovulation with and without adjunctive leuprolide acetate (LA) therapy. DESIGN: Randomized, crossover study of superovulation with and without LA therapy. SETTING: Infertility clinic. PATIENTS: Subfertile patients referred for superovulation and IUI. MAIN OUTCOME MEASURES: Preovulatory serum concentrations of P, E2, and LH on the day of hCG administration; pregnancy. RESULTS: Preovulatory serum concentrations of P, E2, and LH had equivalent predictive value for pregnancy during cycles stimulated without LA therapy. No single parameter was particularly useful in clinical decision making. Threshold P concentrations proposed in other studies as useful in predicting pregnancy did not correlate with cycle fecundity. The predictive value of preovulatory concentrations of P during superovulation with adjunctive LA therapy was significantly worse than P concentrations during superovulation without LA therapy. CONCLUSIONS: Preovulatory serum P, E2, and LH concentrations in superovulation and IUI are not helpful in determining prognosis for pregnancy. The relative utility of predictive parameters may vary for different treatment regimens. PMID- 8495762 TI - Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment. AB - OBJECTIVE: To analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction. DESIGN: Volunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6). SETTING: Tertiary University Institution, Hopital A. Beclere. PATIENTS, PARTICIPANTS: Eighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF. MAIN OUTCOME MEASURE: Plasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies. RESULTS: Cervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls. CONCLUSION: Our results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium. PMID- 8495763 TI - Thyroid hormones in human follicular fluid and thyroid hormone receptors in human granulosa cells. AB - OBJECTIVE: To demonstrate the presence of thyroid hormone in human follicular fluid (FF) and the binding of antithyroid hormone antibodies in human granulosa cells (GCs). DESIGN: Follicular fluids and GCs collected from women undergoing oocyte retrieval after superovulation. SETTING: In Vitro Fertilization America/Allegheny General Hospital and Reproductive Sciences Research Laboratories, the Department of Obstetrics and Gynecology, The Medical College of Pennsylvania/Allegheny Campus. MAIN OUTCOME MEASURES: Follicular fluid levels of triiodothyronine (T3) determined by a microparticle enzyme immunoassay and FF levels of thyroxine (T4) determined by a fluorescence polarization immunoassay. Three anti-thyroid receptor antibodies were used to determine the presence of thyroid receptor. The binding of these antibodies in GCs was assessed by fluorescent microscopy and flow cytometry. RESULTS: Both T3 and T4 were present in the FF of eight patients studied. A large majority of the samples of individual fluids fell within the normal range for serum. There was a positive correlation between serum T4 values and FF T4 values. The three antithyroid receptor antibodies showed positive nuclear staining of GCs by fluorescent microscopy. The antibody to all thyroid hormone receptors yielded 35% positive cells by flow cytometry, and the site specific antibody for either the alpha-1 or beta-1 receptors yielded 78% and 44% positive cells, respectively. CONCLUSION: These data demonstrated, for the first time, the presence of T3 and T4 in human FF and the presence of T3 binding sites in human GCs and suggest a role for thyroid hormone in the regulation of human GCs. PMID- 8495764 TI - Vaginal patterns during danazol and buserelin acetate therapy for endometriosis: structural and ultrastructural study. AB - OBJECTIVE: To evaluate histologic and ultrastructural changes of the vaginal mucosa in patients given buserelin acetate or danazol treatment for endometriosis. DESIGN: Controlled clinical study. SETTING: Infertility clinic of an academic unit. PATIENTS: Infertile women with endometriosis randomized to receive buserelin acetate or danazol and undergoing vaginal biopsies during treatment were selected. INTERVENTIONS: Buserelin acetate was administered IN 400 micrograms three times per day and danazol orally 600 mg/d. Vaginal biopsies were performed baseline and at 3 and 6 months of treatment, and specimens were examined by light microscopy and scanning electron microscopy. 17 beta-Estradiol and P levels were determined in each patient at the time of each biopsy. MAIN OUTCOME MEASURE: Structural and ultrastructural patterns of vaginal mucosa after 3 and 6 months of treatment. RESULTS: Buserelin acetate treatment induced early, marked hypotrophy of the vaginal mucosa with aspects typical of the menopause. The modifications caused by danazol occurred mainly in the intermediate layer, which was weakly hypotrophic only at the end of the treatment. CONCLUSION: Vaginal mucosa undergoes constant and well-defined modifications during both buserelin acetate and danazol treatment for endometriosis. The modifications are compatible with the biological effects of the drugs. PMID- 8495765 TI - Effect of tumor necrosis factor-alpha on adhesion of human endometrial stromal cells to peritoneal mesothelial cells: an in vitro system. AB - OBJECTIVE: To assess the effects of tumor necrosis factor-alpha (TNF-alpha) on adhesion of endometrial stromal cells to peritoneal mesothelial cells, a possible step leading to endometriosis. DESIGN: Analysis of cell adhesion in vitro. SETTING: University research laboratory. PATIENTS: Peritoneal fluid and biopsies were obtained from volunteers with regular cycles without endometriosis or endometrial pathology. INTERVENTIONS: Tumor necrosis factor-alpha (0.1 to 1,000 U/mL) was added to nutrient media with the following supplements: 10% fetal calf serum, epidermal growth factor 20 ng/mL, and gentamicin 10 ng/mL. MAIN OUTCOME MEASURES: Radioactivity of chromium-51 was used as a reflection of adherent stromal cells. RESULTS: The adherence of endometrial stromal cells to mesothelial cells was significantly increased by pretreatment of mesothelial cells with TNF alpha. CONCLUSIONS: Tumor necrosis factor-alpha may play a facilitory role in the development of endometriosis. PMID- 8495766 TI - Significantly enhanced pregnancy rates per cycle through cryopreservation and thaw of pronuclear stage oocytes. AB - OBJECTIVE: To examine the results of a 5-year trial using cryopreservation to limit multiple pregnancy and optimize overall pregnancy per cycle. DESIGN: Retrospective clinical evaluation of pregnancy rates (PRs) per cycle after freezing pronuclear stage human oocytes. SETTING: Tertiary care academic center. PATIENTS: Six hundred seventeen patients treated in 776 IVF-ET cycles from January 1987 to December 1991 (less oocyte donation cycles). MAIN OUTCOME MEASURE: Pregnancy rate per cycle after transfer of pre-embryos developed from thawed pronuclear stage oocytes. RESULTS: Three thousand seven hundred thirty-one oocytes were frozen. Of these, 2,039 were thawed. One thousand three hundred seventy-seven survived thawing (68%), and 1,370 were transferred after passing through syngamy to at least the first cleavage (68%). Of patients with thawing, 359 of 401 (90%) (449 of 505 cycles [89%]) received intrauterine transfer. One hundred thirty-three separate clinical pregnancies were established from 128 different cycles (128/449; 29%); 5 cycles had two thaws, each of which resulted in pregnancy. This PR is less than the overall fresh PR observed in patients who had excess pronucleate oocytes frozen (279/776; 36%) but is remarkably similar when adjusted for the number of pre-embryos transferred per cycle. The age of the patient at the time of cryopreservation and the number of quality of pre-embryos ultimately available for transfer were important factors in the establishment of pregnancy. The mode of ovarian stimulation and duration of cryostorage did not prove meaningful. CONCLUSIONS: Cryopreserved pronucleate oocytes that survive freezing, thawing, and progress through syngamy demonstrate a similar potential for implantation and pregnancy when compared with fresh conceptuses, the cumulative effect of which is an enhanced total PR per cycle. PMID- 8495767 TI - Oocyte donation in low responders to conventional ovarian stimulation for in vitro fertilization. AB - OBJECTIVE: To analyze endometrial response (endometrial dating and implantation) to exogenous administration of E2-valerate and P in women with low response to gonadotropins undergoing oocyte donation. DESIGN: Prospective study. A cycle in which endometrial specimens were obtained and subsequent cycles with ET were evaluated. The control group was made up of patients with premature ovarian failure (POF) undergoing the same procedure. SETTING, PATIENTS: In Vitro Fertilization program at the Instituto Valenciano de Infertilidad. A total of 37 women with low response to gonadotropins in previous cycles and 33 women with POF. INTERVENTIONS: First artificial cycle with E2-valerate and P in the absence of previous pituitary suppression to determine endometrial adequacy. Successive artificial cycles in which ET was performed on cycle day 17. Oocytes donated from infertile patients undergoing IVF. MAIN OUTCOME MEASURES: Serum steroid levels were measured during the artificial cycle. Histologic dating of the endometrium on cycle days 15 and 26. Ultrasonographically documented IVF-ET pregnancies. RESULTS: Postovulatory changes on cycle day 15 were observed in 36.4% of low responders treated with E2-valerate and P in the absence of simultaneous pituitary suppression. Pregnancy rates were higher in women with previous sufficiently (77.8%) or insufficiently (80%) estrogen-primed endometrium than in the cases showing postovulatory changes (37.5%). Pregnancy rates (PRs) per transfer were significantly higher in low responders (63.8%) than in patients with POF (37.2%). Patients with endometriosis had a 71.4% PR per transfer. Embryos derived from oocytes from polycystic ovaries had a 48.3% PR. CONCLUSIONS: Oocyte donation is a reliable alternative for women with low response to gonadotropins, including those with severe endometriosis. The efficacy of the steroid replacement regimen in controlling ovarian function may influence outcome. Thus, women with functional ovaries despite exogenous steroid replacement might be differently treated. Women with polycystic ovaries are an adequate source of oocyte donation. PMID- 8495768 TI - Survey results on the current practice of ovum donation. Ovum Donor Task Force of the Psychological Special Interests Group of the American Fertility Society. AB - OBJECTIVE: To investigate how many programs currently have an ovum donor program and to examine the current state of the art in ovum donor programs regarding management, screening, and implementation. DESIGN: Surveys were sent to members of the Society for Assisted Reproductive Technology (SART) and the Psychological Special Interest Group of the American Fertility Society. RESULTS: Of 160 SART members, 82 surveys were returned. Psychological Special Interest Group surveys were excluded. A trend toward more third party reproduction was seen. There was little uniformity among programs regarding medical or psychological screening. Differences were seen between the screening and administration of ovum and sperm donation. CONCLUSIONS: Unlike sperm donation, ovum donation has begun in the known donor realm. Medical and psychological screening is currently limited in many ovum donor programs and highly variable with both known and anonymous donors. Most programs do use a mental health person as part of the screening process. More guidelines are needed to provide uniformity for the current practice of ovum donation. PMID- 8495769 TI - Human sperm hyperactivation and acrosome reaction and their relationships to human in vitro fertilization. AB - OBJECTIVE: To determine the relationships between human sperm hyperactivation (HA) and acrosome reaction with fertilization of human oocytes in vitro. DESIGN: Prospective analysis of infertile patients undergoing IVF. SETTING: Tertiary center for infertility and assisted reproductive technology. PATIENTS: Fifty-two couples who underwent IVF or GIFT were studied. The male partners had normal semen parameters on routine analyses. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sperm HA in seminal fluid and after 1 and 6 hours incubation in capacitation media; sperm acrosome reaction after 0, 6, and 24 hours' incubation in capacitation media; and fertilization rate of human oocytes. RESULTS: The percent spermatozoa with transitional HA after 6 hours of incubation correlated significantly with the fertilization rate of human oocytes. Multivariate discriminant analyses selected six sperm HA and acrosome reaction variables of predictive value in classifying semen samples that achieved fertilization rates above and below 70% threshold. Combination of the selected sperm HA and acrosome reaction variables in seminal fluid and after different times of incubation in capacitation medium classified the samples achieving good or poor fertilization rate with > 80% accuracy. CONCLUSIONS: Assessment of sperm HA and acrosome reaction may be of prognostic value in prediction of human oocyte fertilization rates. PMID- 8495770 TI - Abnormal sperm-mucus penetration test predicts low in vitro fertilization ability of apparently normal semen. AB - OBJECTIVE: To investigate whether Kremer's sperm-mucus penetration test may predict sperm fertilizing ability in IVF. DESIGN: Kremer's test was prospectively performed on semen samples used for 66 consecutive IVF trials and compared with the fertilization rates and fertilization failure rates observed. RESULTS: Fertilization rates were significantly reduced in cases of abnormal Kremer's test (42% versus 51%; n = 745 oocytes with a statistically insignificant increase in fertilization failure rates (21% versus 10%; n = 66 trials). For abnormal semen, fertilization rates (39% versus 39%; n = 208 oocytes) and fertilization failure rates (20% versus 28%; n = 17 trials) were similar regardless of Kremer's test result. For normal semen, an abnormal Kremer's test implied a significant decrease in fertilization rates (44% versus 54%; n = 537 oocytes) with a statistically insignificant increase in fertilization failure rates (21% versus 6%; n = 49 trials). CONCLUSIONS: Abnormal Kremer's test results identify patients with a decreased in vitro fertilizing ability despite apparently normal semen samples and a group with very low fertilizing failure risk in case of normal semen samples and normal Kremer's test. Kremer's test does not add any predictive value to sperm analysis in the case of abnormal semen samples. These observations point out the importance of the male factor in fertilization failure even in the case of normal semen analysis. PMID- 8495771 TI - Prediction of in vitro fertilization rates from semen variables. AB - OBJECTIVE: To assess the value of semen variables for predicting fertilization rates. DESIGN: Measures of the fresh semen and the motile sperm fraction used for insemination were related to the fertilization rate by multiple regression analysis. The regression model was then used to construct a two-dimensional clinical chart. SETTING: University-affiliated reproductive medicine unit. PATIENTS: The results of 294 IVF cycles were analyzed retrospectively. Selection criteria were: [1] first cycle of IVF; [2] tubal and/or male factor infertility; and [3] four or more oocytes inseminated. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The fertilization rate was related to measured variables of the fresh semen and the motile sperm fraction used for insemination. Fertilization rate was categorized as poor (< 35%) or acceptable (> or = 35%). RESULTS: Multiple regression analysis demonstrated a strong correlation between the fertilization rate and the combined indexes of percentage normal morphology and grade of motility in the fresh semen and percentage progressive motility in the motile sperm fraction. A two-dimensional chart that expressed these relationships was constructed. Its accuracy of prediction was 77% for poor fertilization and 95% for acceptable fertilization. CONCLUSIONS: The fertilization rate is strongly correlated with percentage normal sperm morphology in the fresh semen and the percentage progressive motility in the motile sperm fraction used for insemination. The clinical chart provides a simple but powerful tool for predicting fertilization outcome. PMID- 8495772 TI - A randomized trial of in vitro fertilization versus conventional treatment for infertility. AB - OBJECTIVE: To evaluate the effectiveness of IVF in couples with infertility. DESIGN: Two hundred forty-five consecutive couples with infertility were randomized to receive one cycle of IVF treatment (experimental group) or to wait for a period of 6 months before receiving IVF treatment, during which time other infertility treatments could have been undertaken (control group). SETTING: Patients were referred to the Fertility Clinic at Chedoke-McMaster Hospitals, a university-associated institution in Hamilton, Ontario, Canada, in which IVF has been offered to couples since 1984. PATIENTS: Couples with infertility (mean duration of 65 months) not corrected by conventional treatment. They came from all socioeconomic classes, and the costs of IVF treatment, except medication, were covered by the Ontario Health Insurance Plan. MAIN OUTCOME MEASURE: Pregnancy was confirmed by ultrasound documentation of a gestational sac or histologic examination of tissue. Outcomes included livebirth, spontaneous abortion, and ectopic pregnancy. The overall pregnancy rate (PR) and the interval to-pregnancy duration were compared in each group. RESULTS: Univariate analysis demonstrated a significant beneficial effect of IVF treatment in patients with bilateral severe tubal disease. Although in other diagnostic categories the crude and cumulative PRs in the experimental group were higher than in the control group, the differences did not reach statistical significance. Among the early IVF group, those with endometriosis had significantly more pregnancies when compared with other diagnostic categories. Although IVF increases the likelihood of pregnancy by 40% with severe tubal disease, the overall 31% increase associated with IVF was not statistically significant. CONCLUSIONS: There was a significant difference in favor of treatment in patients with severe bilateral tubal disease. For couples with other causes of infertility, the confidence limits around the treatment effect included unity. To reject the null hypothesis of no treatment effect, a larger sample size or a meta-analysis to combine the results of similar trials is required. PMID- 8495773 TI - Prevention of multiple pregnancies in an in vitro fertilization program. AB - OBJECTIVE: To limit the high number of multiple pregnancies in an IVF program. SETTING: In Vitro Fertilization Laboratory, Fertility Department, Public Hospital. INTERVENTIONS: The number of embryos transferred was limited to two instead of three. RESULTS: Limiting the number of embryos transferred to only two did not influence the take home baby rate but eliminated triplet and quadruplet gestations. Moreover, the number of patients with good quality supernumerary embryos available for cryopreservation increased. CONCLUSIONS: To reduce the high frequency of multiple gestations in an IVF program, the number of embryos replaced should be limited to a maximum of two. PMID- 8495774 TI - The luteal phase after ovulation induction with human menopausal gonadotropin and one versus two doses of a gonadotropin-releasing hormone agonist. AB - OBJECTIVE: To use a GnRH agonist (GnRH-a) to induce ovulation after priming with exogenous hMG. DESIGN: Prospective, randomized double-blind protocol using one or two doses of intranasal nafarelin. SETTING: Office-based ovulation induction program. PATIENTS, INTERVENTIONS: Infertile women not conceiving after use of clomiphene citrate for at least 6 months who were given hMG and nafarelin. No luteal support was given. MAIN OUTCOME MEASURES: Serum concentrations of FSH, LH, E2, and P acutely and at 6 days after GnRH-a administration. Duration of the luteal phase was assessed. RESULTS: Ovulation with elevation of both FSH and LH was achieved. The two-dose regimen was more effective than one dose for sustained LH release. Luteal phase P values and luteal phase duration were both less than usually seen with gonadotropin hCG therapy in the absence of luteal phase support. CONCLUSIONS: Ovulation induction with GnRH-a after hMG priming produces unacceptable luteal phase cycles in the absence of hormonal support. PMID- 8495775 TI - Sperm motion parameters after suppression of spermatogenesis with a gonadotropin releasing hormone antagonist plus testosterone supplementation. AB - OBJECTIVE: To evaluate whether the chronic administration of a GnRH antagonist supplemented with T enanthate affects sperm motion parameters. DESIGN: Prospective study. SETTING: Academic medical research environment. PATIENTS/PARTICIPANTS: Six normospermic men of reproductive age. INTERVENTION: A 20-week treatment included the administration of 10 mg of GnRH antagonist every day and 25 mg of T enanthate once a week. MAIN OUTCOME MEASURE: Computerized sperm motion analysis on each participant every 2 weeks for a period of 11 months. RESULTS: Sperm concentration decreased after 4 weeks of the GnRH antagonist administration, accompanied by a reduction of sperm motility from an initial mean value of 56% to 34% on treatment week 4 and 21% on treatment week 6. In contrast, sperm velocity, linearity, amplitude of the lateral head displacement, and beat cross-frequency values did not significantly change in spite of reduced overall sperm concentration and motility. Azoospermia was reached within 6 to 12 weeks of the GnRH administration, and it was sustained during the treatment period. During recovery of spermatogenesis, sperm movement parameters returned to initial values earlier than sperm concentration and normal morphology. All participants recovered initial semen parameters 20 weeks after the end of treatment. CONCLUSION: The administration of a GnRH antagonist supplemented with T enanthate successfully induced reversible suppression of spermatogenesis. The sperm motion characteristics appeared to be the last parameters to decline and the first to return to initial values after the treatment. PMID- 8495776 TI - Effect of platelet-activating factor, lyso-platelet-activating factor, and lysophosphatidylcholine on sperm motion: importance of albumin for motility stimulation. AB - OBJECTIVES: To determine the effect of platelet-activating factor (PAF), the PAF derivative lyso-PAF, and lysophosphatidylcholine on in vitro sperm motility and to determine the role of albumin in this interaction. DESIGN: Washed human spermatozoa were exposed to a range of PAF, lyso-PAF, or lysophosphatidylcholine concentrations, supplemented with different albumin concentrations, and the effect on sperm motion was quantified with a computer-assisted motion analysis. The metabolism of these compounds by spermatozoa was also assessed. SETTING: University research laboratory. PATIENTS, PARTICIPANTS: Semen samples were obtained from donors and patients attending an infertility clinic. INTERVENTIONS: Human spermatozoa were incubated with PAF, lyso-PAF, or lysophosphatidylcholine at 10(-11) to 6 x 10(-4) M, with 0% to 1.2% albumin, and motility was evaluated at different time periods from 5 to 240 minutes. Tritiated PAF, lyso-PAF, or lysophosphatidylcholine was incubated with spermatozoa, and the metabolites were separated and quantified by thin-layer chromatography (TLC). MAIN OUTCOME MEASURES: Sperm motion characteristics, including the percentage of motile spermatozoa, velocity, and linearity, and sperm viability were determined. The metabolism of PAF, lyso-PAF, and lysophosphatidylcholine by spermatozoa was also studied. RESULTS: Fifty micromolar of PAF and 100 microM lyso-PAF, supplemented with 0.3% albumin, increased sperm linear velocity by 41% +/- 5% (+/- SEM) and 44% +/- 5% and curvilinear velocity by 17% +/- 3% and 21 +/- 3%, respectively. Lysophosphatidylcholine had a similar effect but only at 22 degrees C and not 37 degrees C. In the absence of albumin, neither PAF, lyso-PAF, or lysophosphatidylcholine induced increases in sperm motion. Lysophosphatidylcholine and lyso-PAF are not detectably metabolized by spermatozoa, whereas 12.5% +/- 1.2% of PAF is hydrolyzed to lyso-PAF in 1 hour. CONCLUSION: Platelet-activating factor, lyso-PAF, and lysophosphatidylcholine independently stimulate sperm linear and curvilinear velocity. This action requires albumin. These compounds may be of use in the treatment of asthenozoospermic males. PMID- 8495777 TI - Novel parameters of human sperm hypoosmotic swelling test and their correlation to standard spermatogram, total motile sperm fraction, and sperm penetration assay. AB - OBJECTIVE: To improve the accuracy of human sperm hypoosmotic swelling test by introducing new morphological evaluation parameters for this test. DESIGN: Individual semen samples were processed, and the standard spermatogram, total motile sperm fraction, sperm penetration assay (SPA), and hypoosmotic swelling test were performed. SETTING: Male infertility clinic and andrologic laboratory in a university medical center. PATIENTS: One hundred eighteen subfertile men undergoing an infertility work-up. MAIN OUTCOME MEASURES: The results of hypoosmotic swelling test were subdivided into four groups (hypoosmotic swelling test 1, 2, 3, 4) according to the different shapes of hypoosmotically affected spermatozoa tails. RESULTS: The hypoosmotic swelling test 3 had the best correlation with the different sperm parameters: motility, total motile sperm fraction, concentration, and SPA. The hypoosmotic swelling test 1 showed a satisfactory interrelation for concentration and for total motile sperm fraction but no correlation for motility and SPA. The hypoosmotic swelling test 2 and the hypoosmotic swelling test 4 demonstrated no correlation at all with motility, concentration, morphology and SPA. CONCLUSIONS: The precision of hypoosmotic swelling test may be improved by using the hypoosmotic swelling test 3 type of spermatozoa tail shape as the parameter for a normally functioning spermatozoa. PMID- 8495778 TI - The use of the stimulated acrosome reaction test as a test of fertilizing ability in human spermatozoa. AB - OBJECTIVE: To assess if patients who do not fertilize human oocytes in vitro can be identified by a lack of acrosomal response of their spermatozoa to stimulation by the calcium ionophore A23187. DESIGN: The stimulated acrosomal response for all patients was calculated. Those not achieving fertilization were compared with a normogram constructed from donors and patients who achieved fertilization; the 0.5th centile (31.3% increase in the number of spermatozoa reacted) was used as a discriminant point. PATIENTS: Fifty-four IVF patients and 15 fertile sperm donors. SETTING: An outpatient based IVF program. INTERVENTIONS: Acrosome reaction stimulated by 2 hours incubation in a 5-mumol/L solution of the calcium ionophore A23187. RESULTS: Patients who fertilized oocytes responded as donors. Eight of 16 patients failing to fertilize oocytes showed a minimal increase in the number of acrosome-reacted spermatozoa (mean [+/- SD] rise 6.3% +/- 10.3%). An acrosomal response of < 31.3% predicts fertilization failure in 100% of cases. CONCLUSIONS: Failure of the acrosome to react is responsible for some failure of IVF. PMID- 8495779 TI - Effects of modulators of protein kinase C on human sperm capacitation. AB - OBJECTIVE: To examine the effects of stimulators or inhibitors of protein kinase C on capacitation and protein phosphorylation in human sperm. DESIGN: Capacitated sperm treated with or without modulators of protein kinase C were monitored by the chlortetracycline fluorescence assay. Capacitation was confirmed by the ability of sperm to undergo the acrosomal reaction in response to mouse zonae pellucidae. 32P-labeled sperm phosphoproteins were analyzed by one-dimensional gel electrophoresis to detect the effect of protein kinase C stimulator, 12-O tetradecanoyl-phorbol-13-acetate, on protein phosphorylation. RESULTS: The treatment of sperm with protein kinase C stimulators resulted in the following: [1] the rapid appearance of the clear perimeter pattern, featuring distribution of fluorescence over the entire head exhibiting a bright perimeter and bright midpiece; [2] an accelerated ability to undergo the acrosomal reaction; and [3] an enhanced phosphorylation of 57.5-kd sperm phosphoprotein. Furthermore, these stimulatory effects were inhibited by protein kinase C inhibitors. CONCLUSION: Protein phosphorylation mediated by protein kinase C may be involved in the regulation of human sperm capacitation. PMID- 8495780 TI - A new mouse model for embryos with a hatching deficiency and its use to elucidate the mechanism of blastocyst hatching. AB - OBJECTIVE: To develop an experimental model for embryos with a defect specific to hatching, with the purpose of clarifying the mammalian embryo hatching mechanism. DESIGN: A microneedle was inserted under the zona pellucida (ZP) of mouse embryos, and either 1/2 or 1/4 of the blastomeres were mechanically destroyed. The remainder of embryos that developed into blastocysts were compared for hatching to controls wherein a microneedle was inserted and withdrawn without harming the embryo. Experiments were done to increase pressure within the perivitelline space to decrease the amount of ZP material to study the hatching mechanism. SETTING: University-based basic research laboratory. RESULTS: When 1/2 or 1/4 of the embryo was destroyed and the remaining cells developed into healthy blastocysts within the intact zona, hatching was significantly impaired, and zona thickness was markedly increased relative to controls. When a mineral oil droplet was inserted under the zona to enhance a possible mechanical component of hatching, manipulated embryos were not restored to normal hatching, and hatching of unmanipulated blastocysts was not improved. However, when the zona was circumferentially thinned by application of acid Tyrode's solution, the hatching defect in manipulated "3/4 embryos" was corrected. CONCLUSION: Because it is known that embryos with cells reduced by 1/2 or 1/4 have normal developmental potential, we conclude that the inability of such embryos to hatch from an intact zona constitutes a mouse model for a defect specific to hatching. Moreover, results from mineral oil droplet insertion and circumferential thinning of the zona indicate that normal hatching is accomplished predominantly, if not entirely, by zona lysis, not by pressure exerted against the zona by the expanding blastocyst. PMID- 8495781 TI - Restoration of normal implantation rates in mouse embryos with a hatching impairment by use of a new method of assisted hatching. AB - OBJECTIVE: To use a newly developed mouse model for embryos with a hatching defect to develop improved methods of assisted hatching. DESIGN: We had previously demonstrated that mouse embryos with reduced cell numbers, when resident within an intact zona, exhibit a hatching deficiency, and we used these "hatching-defective" embryos to demonstrate that hatching is mediated predominantly, if not entirely, by lysis of the zona pellucida. In the present study, the hatching-defective embryos were implanted into pseudo-pregnant females to determine if implantation rates were reduced. In addition, to compensate for reduced zona lysin production, the zonae of some embryos were circumferentially thinned with acid Tyrode's solution. The implantation rates and developmental potential of hatching-defective embryos subjected to zona thinning were compared with those of the hatching-defective embryos implanted without zona thinning. SETTING: University-based basic research laboratory. RESULTS: When hatching defective embryos, created by destruction of 1/4 of the blastomeres at the four cell stage, were implanted into pseudopregnant female mice, no pregnancies were established, and no implantation sites could be identified after transfer of 41 embryos. However, when hatching-defective embryos were subjected to zona thinning before ET, a normal rate of implantation was observed (18 implantation events of 49 embryos transferred). Fetuses appeared morphologically normal. The difference in implantation rates between hatching-defective embryos subjected to zona thinning and those not treated by zona thinning was highly significant by chi 2 analysis. CONCLUSION: Failure of embryos with cell numbers reduced by micromanipulation to implant and restoration of normal implantation and development after circumferential zona thinning demonstrates that the developmental defect of the manipulated embryos is confined to hatching, and thus, that this procedure establishes a useful model for defective hatching. High rates of implantation after circumferential thinning of the zona shows that this procedure of assisted hatching is highly effective. These findings have important implications for use of assisted hatching in human IVF because the assisted hatching procedure is safe and effective and increases the efficiency of the normal hatching mechanism. Thus, the procedure may be useful in a wide variety of circumstances for which assisted hatching by zona opening has been found to be ineffective. PMID- 8495782 TI - A successful pregnancy after subzonal insertion with epididymal sperm and coculture on Vero cell monolayer. AB - A 26-year-old nulliparous woman conceived after transfer of three embryos cocultured on a Vero cell monolayer. The ET followed SUZI of epididymal sperm from her husband with congenital absence of vas deferens. PMID- 8495783 TI - Successive transperitoneal migration of ova in a woman with extensive pelvic adhesions. AB - Our case report describes three conceptions after transperitoneal migration of the ovum in a woman with only one ovary, the contralateral oviduct, and extensive postoperative pelvic adhesions obliterating the Douglas cul-de-sac. This suggests that anatomic integrity of the pelvis is not always essential for ovum pick-up. PMID- 8495784 TI - Severe abdominal complications after transvaginal ultrasonographically guided retrieval of oocytes for in vitro fertilization and embryo transfer. AB - Severe life-threatening complications as a result of ultrasonically guided ovum pick-up for IVF may rarely occur. We report 14 cases, out of 3,656 patients undergoing the procedure, presenting with a clinical picture of acute abdomen. In 9 patients tubo-ovarian and pelvic abscess were diagnosed; 3 were treated by laparotomy, whereas in the other 6, culdocentesis and drainage were performed. In 3 cases severe intra-abdominal bleeding occurred with 1 requiring laparotomy and hemostasis, whereas in the others laparoscopic drainage and hemostasis were sufficient. Ruptured endometriotic cystic masses caused acute abdomen in 2 patients; partial oophorectomy and drainage were essential operative procedures. We conclude that although severe postovum retrieval complications are rare, one has to be aware of their occurrence with the aim of accurate diagnosis and prompt intervention. PMID- 8495785 TI - Histopathology of the fallopian tube after local instillation of hyperosmolar glucose solution for unruptured tubal pregnancy. AB - Because of an incomplete tubal abortion, salpingectomy was performed in a patient 12 days after glucose instillation into an ampullary tubal gestation. Serum hCG levels had progressively declined from 1.122 mIU/mL at first intervention to 37 mIU/mL at the second operation. Histopathology showed marked necrosis of trophoblastic tissue but no discernible damage of the tubal epithelium and tubal wall attributable to the hyperosmolar solution applied 12 days before. This case offers histopathologic evidence that intraluminal glucose instillation for treatment of unruptured tubal pregnancies does not lead to persisting damage of the tubal mucosa. PMID- 8495786 TI - The straw swim-up: a simple method to evaluate the effects of additives, media, or toxicants on sperm motility. AB - We describe a new method for evaluating potential toxicants, spermicides, and motility enhancers. Cryopreservation straws filled with media plus additive are emersed below the surface of an unprocessed donor ejaculate. After incubation, the sperm found within the first 4 cm of the straw are expelled and analyzed. The effects of media containing glycerol and albumin were examined. Survivability and sperm migration into the media occur independently and can be differentiated in this assay. This method allows for the use of unprocessed semen and includes an evaluation of the semen and media interaction. PMID- 8495787 TI - Combined transvaginal tubal catheterization and adhesiolysis of filmy uterine synechiae performed with a newly developed device under the guidance of digital road mapping fluoroscopy. AB - Transcervical fallopian tube catheterization is rapidly gaining favor as a minimally invasive diagnostic and therapeutic technique. On occasion, the presence of filmy adhesions not identified on HSG obstruct the passage of the cannula to the cornual angle. We describe the design and operative characteristics of a new transcervical adhesiolysis device that if used under the guidance of DRM mapping, can restore the shape of the uterine cavity and allow completion of the procedure during the same session. PMID- 8495788 TI - A novel technique for cervical cannulation during hysterosalpingography. AB - In this series 40 patients presenting for HSG had cervical stenosis impeding cervical cannulation with an acorn tip catheter. Successful cervical cannulation was obtained in all instances, using a modified tom cat catheter as described. Successful visualization of the uterine cavity was achieved in all 40 patients. PMID- 8495789 TI - Value of myomectomy in the treatment of infertility. PMID- 8495790 TI - Value of myomectomy in the treatment of infertility. PMID- 8495791 TI - [Closure of cleft palate in adults using a microvascular radial artery flap from the forearm. I]. PMID- 8495792 TI - [Speech characteristics of persons wearing full upper and lower prostheses]. AB - We've taken under comparative examination the phonation of people having full upper and lower dentures and the ones having normal teeth. We've tested twenty 51 to 65 years old persons having their dentures at least for a year being pleased with them (well speaking and chewing normally) and twenty persons (without distinction as to sex) having normal teeth normal occlusion. The investigation of the articulation was compiled a lingual corpus consisted of texts of different length (words, word-groups, sentences and text-pieces). This material was suitable for the examination of disorders of the articulation, the pronunciation of the sound combinations, the articulatory problems, and the suprasegmental components (e.g. melody, speech tempo, dynamics of speech). The experimental material was prepared by the following instruments: an VII (Voice Identification, Inc.) 700 series sound spectrograph, an IBM compatible computer with acoustic analytical programs suitable for the investigation of selected sound samples by an A/D (analog/digital) converter, the number of sounds in a second was measured with a 8SO-4 type oscillograph. The results can be summarized as follows: 1. various differences appear among the speech structures of persons having full upper and lower dentures: the labial [b p m], labiodental [v f ], dental, dentialveolar [d t n z s dz ts l r], alveolar [symbol: see text] and prepalatal [symbol: see text] consonants distort principally. 2. From the long consonants the voicelles stops (p: t: k:) are short-ended especially.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495794 TI - [66th annual meeting of the Japan, Endocrine Society. Kanazawa, Japan June 3-5, 1993. Abstracts]. PMID- 8495793 TI - [Experience with Ketac silver filling material]. AB - The authors used ESPE's Ketac silver "cermet" in deciduous molars. They advise to use it only in deciduous teeth because of its low wearing quality and britleness. PMID- 8495795 TI - Anterior pituitary glandular kallikrein: a putative prolactin processing protease. PMID- 8495796 TI - Identification and characterization of an early estrogen-regulated RNA in cultured guinea-pig endometrial cells. AB - A cDNA library was prepared from quiescent guinea-pig endometrial glandular epithelial cells stimulated for 2 h with estradiol-17 beta (E2) in the presence of cycloheximide. It was screened by differential hybridization for estrogen regulated sequences. Six recombinants containing E2-regulated sequences were identified. One of them, called gec1 was then characterized by Northern blot hybridization. The gec1 mRNA was 1,800 bases in size. A 2-fold increase in the gec1 mRNA level was achieved at 120 min after E2 treatment. The E2 action on gec1 gene required the presence of cycloheximide. The cloned gec1 cDNA was 1 kb in size. The sequence so far determined did not show similarity with well characterized genes. This is the first report on a cloned cDNA probe of early estrogen-induced mRNA in a primary culture of endometrial epithelial cells. PMID- 8495797 TI - Altered steroidogenic activity of human granulosa-lutein cells at different cell densities in culture. AB - In the present study, the relationship between human granulosa-lutein cell (hGLC) plating density and steroidogenic activity was evaluated. Increasing hGLC-plating density 32-fold, from 0.25 x 10(4) to 8 x 10(4) cells/well, was associated with a concomitant increase in the total amount of progesterone (P4), testosterone (T), and estradiol-17 beta (E2) secretion. The daily amount of each steroid (P4, T, and E2) secreted by hGLC at different cell-plating densities was further normalized per 10(3) cells. Thus, an increase in hGLC-plating density from 0.25 x 10(4) to 1 x 10(4) cells/well was associated with approximate increases of 1.3 fold in P4 and 3-fold in T and a 50% decrease in E2 secretion, per 10(3) cells. A further increase in hGLC-plating density, from 1 x 10(4) to 8 x 10(4) cells/well, was associated with a significant decrease of approximately 3.7-fold in P4 and 6 fold in T per 10(3) cells. A similar increase in hGLC-plating density was associated with no change or a 2-fold decrease, per 10(3) cells, in E2 secretion during days 0-3 or days 3-5 of culture, respectively. The P4/E2 ratio was increased and the E2/T ratio decreased with extension of the culture period. These two ratios had a tendency to be altered inversely, concurrent with the increase in cell-plating densities. At 1-2 x 10(4) cells/well, P4/E2 was maximal, whereas E2/T was minimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495798 TI - Translational control of ornithine-delta-aminotransferase (OAT) by estrogen. AB - Ornithine-delta-aminotransferase (OAT) catalyzes the reversible transamination of ornithine to glutamate semialdehyde. OAT is abundant in liver, kidney and retina; hereditary deficiency of the enzyme leads to chorioretinal degeneration. Studies of OAT regulation in retinoblastomas have revealed an alternatively spliced OAT mRNA, which contains an additional exon (exon 2) in the 5' untranslated region. Estrogen and thyroid hormone were previously shown to increase OAT mRNA levels approximately 3-fold and 5-fold, respectively, in these cells. To determine the mechanism of hormonal action in retinoblastomas, we performed nuclear transcription assays and analyzed the distribution of OAT mRNAs in individual fractions of a polysome gradient. Thyroid hormone increased the rate of transcription of the OAT mRNA in these cells. Estrogen did not stimulate transcription; it was associated with increased translation, since it resulted in a shift of the major (spliced) OAT mRNA species into denser fractions of the polysome gradient. Cycloheximide treatment suggested that the latter effect was due to increased initiation of translation. The unspliced OAT mRNA, which is inefficiently compared to the spliced mRNA, was insensitive to estrogen in these experiments. PMID- 8495799 TI - In situ detection and distribution of stanniocalcin mRNA in the corpuscles of Stannius of sockeye salmon, Oncorhynchus nerka. AB - Stanniocalcin (STC) gene expression was examined in the corpuscles of Stannius of sockeye salmon by in situ hybridization. Generally, the STC gene was not expressed uniformly in all cells of the corpuscles of Stannius. However, in cases where gene expression was uniform throughout a gland, it appeared that virtually all cells contained STC mRNA, thereby supporting the 'one cell type' hypothesis for the corpuscles of Stannius. Correlative immunocytochemistry on adjacent tissue sections indicated that cellular levels of stored hormone paralleled the distribution of STC mRNA. Stanniocalcin mRNA was undetectable in numerous other salmon tissues, thereby further supporting the notion that the STC gene is expressed exclusively in the corpuscles of Stannius. PMID- 8495800 TI - Developmental changes in cyclic AMP-dependent protein kinase associated with increased secretory capacity of Manduca sexta prothoracic glands. AB - In Manduca sexta, basal and PTTH-stimulated secretion of ecdysteroids by prothoracic glands in vitro increases from days 1 to 4 of the fifth larval stage. Glandular content of cAMP-dependent protein kinase was analyzed to determine if the enzyme changes in concert with increased secretory response. Photoaffinity labeling with [32P]8-N3 cAMP revealed a 55-kDa cAMP-binding protein characteristic of the regulatory subunit of type-II cAMP-dependent protein kinase (RII). It appears that RII is one of a limited number of cellular proteins that is phosphorylated in the presence of [gamma-35S]ATP; the thiophosphorylated protein and the photoaffinity-labeled regulatory subunit possess the same M(r) and pI, and thiophosphorylation is blocked by mammalian cAMP-dependent protein kinase inhibitor. From days 1 to 4 of the fifth instar, glandular content of RII increases in conjunction with increased ecdysteroid secretory capacity. Application of JH analog on day 1 significantly inhibits the observed increase in RII. Catalytic subunit activity does not change from days 1 to 4 of the fifth instar, nor does cellular content of a 34-kDa protein previously shown to be phosphorylated in response to PTTH. While it is unlikely that increased content of RII is solely responsible for enhanced ecdysteroid secretion by the prothoracic glands, it may serve as a convenient marker for investigating the mechanism by which steroidogenic capacity is regulated. PMID- 8495801 TI - Glucocorticoid regulation of G-protein subunits in neonatal liver. AB - The effect of dexamethasone administration in vivo on the steady-state levels of G-protein subunits in liver of neonatal rabbits was investigated using specific antibodies to each subunit as well as bacterial toxin-mediated ADP-ribosylation assays. Parallel measurements were also made of the activity of adenylyl cyclase, as influenced by a variety of activators. Dexamethasone administration modulated the levels of G-protein subunits in liver in an age-dependent and subunit specific manner but not in 24-h-old newborns. The inductive effect of dexamethasone was observed in animals older than 24 h, the greatest effect being on 2- to 3-day-old neonates. In 48-h-old animals the alpha-subunits Gs alpha-1, Gs alpha-2, Gi alpha and the beta-subunit G beta increased 2.0-, 2.1-, 4.3- and 2.8-fold, respectively, compared to the control. The increases were much less for older animals. Dexamethasone treatment also modulated effector-mediated stimulation of adenylyl cyclase activity in vitro and mimicked its effects on G protein levels; the greatest increase (approximately 2-fold) in the activation of adenylyl cyclase occurred in membranes isolated from 2- to 3-day-old animals. In older animals there was either no effect of dexamethasone or a decrease in activity. The degree of change in enzyme activity paralleled the change in the amount of Gs alpha rather than of Gi alpha or G beta. These results suggest development-dependent regulation of hepatic G-proteins by glucocorticoids. PMID- 8495802 TI - Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis. AB - Smooth-muscle cells cultured from the penis of sexually immature (I-PSMC) and adult (A-PSMC) rats express similar high levels of the androgen receptor (AR) mRNA. This contrasts with the marked in vivo decline of both AR mRNA and androgen binding in the penile smooth muscle of adult rats, which appears to be responsible for the cessation of androgen-dependent penile growth upon sexual maturation. PSMC is therefore a good model to study putative down-regulators of AR expression as a function of cell proliferation in the smooth muscle of androgen-responsive vascular tissue. In order to determine whether AR protein levels in PSMC correlate with AR mRNA levels, the immunocytochemical detection of ARs and their androgen binding capacity were compared between I- and A-PSMC. The number of ARs and their protein half-lives suggested similar levels of translation of the AR mRNA in both cell lines. The effect of the synthetic analog methyltrienolone (R-1881) on androgen binding was studied in contact-inhibited androgen-deprived PSMC. In contrast to the postulated role of androgens as down regulators of AR expression in rat penis, ARs were up-regulated in A-PSMC by R 1881. Contact inhibition of A-PSMC combined with serum depletion and androgen deprivation down-regulated AR mRNA levels, and dihydrotestosterone (DHT) counteracted this effect. These results suggest that the loss in A-PSMC of the age-dependent down-regulation of ARs observed in vivo in adult corpora cavernosa smooth muscle is related to the in vitro resumption of cell proliferation and that DHT acts directly on the penile smooth muscle as a positive modulator of AR levels. PMID- 8495803 TI - Hyperglycemic pseudohypoxia and diabetic complications. AB - Vasodilation and increased blood flow are characteristic early vascular responses to acute hyperglycemia and tissue hypoxia. In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD+ and the resulting increased ratio of NADH/NAD+. In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD+, in this case because of an increased rate of reduction of NAD+ to NADH. Several lines of evidence support the likelihood that the increased cytosolic ratio of free NADH/NAD+ caused by hyperglycemia, referred to as pseudohypoxia because tissue partial pressure oxygen is normal, is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural function and plays an important role in the pathogenesis of diabetic complications. These effects of hypoxia and hyperglycemia-induced pseudohypoxia on vascular and neural function are mediated by a branching cascade of imbalances in lipid metabolism, increased production of superoxide anion, and possibly increased nitric oxide formation. PMID- 8495804 TI - Abnormal activity in diabetic rat saphenous nerve. AB - This study was conducted to test whether abnormal spontaneous activity similar to that found after peripheral nerve trauma develops in diabetic nerve, and whether duration and/or severity of hyperglycemia affected ongoing activity. We maintained 32 diabetic BB Wistar rats on a euglycemic or hyperglycemic control regimen for 3-15 mo; 22 nondiabetic BB rats served as controls. All animals underwent acute saphenous nerve recordings. Whole nerve conduction velocities in 3- to 6-mo-old euglycemic diabetic rats were not different from controls, but 3- to 6-mo-old hyperglycemic diabetic conduction velocities were slower than in controls (P < 0.001) or euglycemic diabetic rats (P < 0.05). Compared with controls, 9- to 12-mo-old diabetic nerve conduction velocities were slower under both euglycemic (P < 0.029) and hyperglycemic (P < 0.04) regimens, but treatment groups did not differ. Combined 3- to 6-mo-old diabetic rats exhibited less resting sympathetic activity than controls under both euglycemic (P < 0.022) and hyperglycemic (P < 0.001) regimens. Sympathetic activity in 9- to 12-mo-old diabetic rats did not differ from controls. However, less sympathetic activity was found in older controls than in younger ones (P < 0.028). IN CONCLUSION: 1) saphenous nerve conduction velocity was slower in diabetic BB rats than in controls; 2) good glycemic control maintained normal conduction velocity in young adults, but the effect diminished with age; 3) resting sympathetic activity levels in young adult BB rats were lower than controls; and 4) sympathetic activity in old BB rats was diminished whether diabetes was present or not. PMID- 8495805 TI - Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs. AB - To investigate a possible role of excessive polyol production in the pathogenesis of diabetic retinopathy, 16 ALX-induced diabetic dogs and 20 experimentally galactosemic dogs were randomly assigned to 5 yr of treatment with either sorbinil, an aldose reductase inhibitor, or a placebo. The severity of hyperglycemia in sorbinil-treated and placebo groups was monitored throughout the 5-yr study by assay of glycosuria and nonenzymatically glycated plasma protein and HbA1 needed in an effort to avoid confounding possible group differences in hyperglycemia severity with possible drug effects. Inhibition of polyol production by sorbinil was monitored in erythrocytes throughout the study and also in retina and other tissue obtained at autopsy. Trypsin digests of retinal vessels were compared after 60 mo of diabetes and after 42 and 60 mo of galactosemia. In diabetic dogs, development of retinopathy was not significantly influenced by a sorbinil dose (20 mg.kg-1 x day-1) sufficient to prevent elevation of sorbitol levels in retina and other tissue. Likewise, in dogs made experimentally galactosemic for 42-60 mo, administration of sorbinil (60-80 mg.kg 1 x day-1) had no significant effect on the development of retinopathy notwithstanding prevention of 93-96% of the polyol elevation in retina and other tissue. Retinal capillary basement membrane was significantly thicker than normal in diabetic and in galactosemic dogs and was not significantly influenced by administration of sorbinil in either dog model. Thus, no evidence was found that the development of retinopathy is critically dependent on excessive polyol production or accumulation. PMID- 8495806 TI - Immunochemical detection of advanced glycation end products in renal cortex from STZ-induced diabetic rat. AB - To reassess the accumulation of advanced glycation end products in diabetic renal cortex, we used a newly developed enzyme-linked immunosorbent assay to measure AGEs in renal cortex from STZ-induced diabetic and age-matched control rats. Kidneys and aortas were obtained from rats after 5 and 20 wk of STZ injection. At 5 wk of diabetes, the mean AGE content in collagenase-digested materials of renal cortex was > 16-fold higher in diabetic animals compared with controls (1044.4 +/ 151.8 vs. 64.3 +/- 5.7 arbitrary units, P < 0.01). At 20 wk of diabetes, it was > 45-fold higher in diabetic compared with control animals (3841.0 +/- 1077.3 vs. 83.8 +/- 12.8 AUs, P < 0.01). These increases were surprisingly large compared with the < 1.5-fold increase in the fluorescence levels both after 5 and 20 wk of diabetes. In control animals, neither the AGE content nor the fluorescence level increased during this period. Moreover, at 20 wk of diabetes, the AGE content was 39-fold higher in renal cortex compared with aorta. This study provided the first immunochemical evidence that collagenase-digested materials of renal cortex, as well as aorta, contained AGE products and that these products were present in much higher levels in diabetic animals than in control animals. With duration of diabetes, the AGE contents increased significantly both in renal cortex and aorta. The excessive accumulation of AGEs was most apparent in the diabetic kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495807 TI - Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. AB - The effects of short-term hyperinsulinemia on the production of both VLDL triglyceride and VLDL apoB were determined semiquantitatively before and during a 6-h euglycemic hyperinsulinemic clamp (40 mU.m-2 x min-1) in 17 women (8 chronically hyperinsulinemic obese, BMI = 35.7 kg/m2; 9 normal weight, BMI = 22.5 kg/m2). During acute hyperinsulinemia, plasma FFA decreased by approximately 95% within 1 h in both groups. VLDL triglyceride production decreased 66% in the control subjects (P = 0.0003) and 67% in obese subjects (P = 0.0003). ApoB production decreased 53% in control subjects (P = 0.03) but only 8% in obese (NS). Plasma triglycerides decreased by 40% from baseline in control subjects (P < 0.0001) but only by 10% in obese subjects (P = NS). Despite the similar decrease in triglyceride and apoB production in control subjects, VLDL particle size (triglyceride-to-apoB ratio) decreased with hyperinsulinemia (P = 0.003). In obese subjects, despite a decrease in triglyceride production similar to that in control subjects but no change in apoB production, VLDL size did not change appreciably. Acute hyperinsulinemia in humans: 1) suppresses plasma FFA equally in control and obese subjects at this high dose of insulin; 2) inhibits VLDL triglyceride production equally in control and obese subjects, perhaps secondary to the decrease in FFA; 3) inhibits VLDL apoB production in control but less so in obese subjects, suggesting that obese subjects may be resistant to this effect of insulin; 4) decreases plasma triglyceride and VLDL particle size in control subjects, reflecting either stimulation of LPL activity or a greater relative decrease in triglyceride to apoB production; and 5) does not decrease plasma triglyceride or VLDL size in obese subjects to the same extent as it does in control subjects. Thus, the insulin resistance of obesity affects some but not all aspects of VLDL metabolism. PMID- 8495808 TI - 5' insulin gene polymorphism confers risk to IDDM independently of HLA class II susceptibility. AB - The polymorphic variable number of tandem repeats in the 5' upstream region of the human insulin gene is a well-known non-human leukocyte antigen locus contributing to genetic susceptibility to IDDM. Controversy exists about the question as to whether INS susceptibility haplotypes are or are not preferentially inherited together with HLA-DR4 haplotypes. We investigated whether genetic interaction between INS and the HLA complex can be better defined using DQ genotypic and phenotypic markers in addition to DR serology. The 5' INS 1/1 genotype was positively associated with IDDM both in non-DR4 subjects (relative risk = 4.3; 95% confidence interval, 1.6-11.5) and DR4 subjects (relative risk = 4.2; 95% confidence interval, 1.9-9.0). Further subdivision of IDDM patients and matched control subjects according to HLA-DQA1 and HLA-DQB1 genotype or phenotype also failed to show any association between 5' INS and HLA class II genes in diabetic patients. The 5' INS and HLA class II polymorphisms therefore provide independent risk markers, which may both contribute to the genetic screening of a high-risk population among nondiabetic individuals. PMID- 8495809 TI - Oscillatory insulin secretion after pancreas transplant. AB - In vivo studies of beta-cell secretory function have demonstrated the existence of rapid insulin oscillations of small amplitude recurring every 8-15 min in normal subjects. This study evaluated the effects of pancreas transplant on rapid insulin oscillations. Samples for glucose, insulin, and C-peptide were drawn during constant glucose infusion at 2-min intervals for 90 min from six successful Px patients with type I diabetes mellitus, from six normal nondiabetic control subjects, and from three Kx subjects. A computerized algorithm (ULTRA) was used for pulse detection. In the Px group, the average insulin pulse period was significantly shorter than in both the control and Kx groups (Px 8.1 +/- 0.5, control 12.5 +/- 0.7, Kx 12.4 +/- 0.5 min, P < 0.0005). By contrast, the C peptide pulse periods (Px 16.8 +/- 2.3, control 14.7 +/- 1.2, Kx 15.3 +/- 1.5 min) were similar in the three groups. Spectral analysis confirmed that the frequency of the insulin pulses was increased in the Px group. The absolute amplitude of the insulin pulses was greater in the Px group (P < 0.001) while the amplitude of the C-peptide pulses did not differ between the groups. Cross correlation analysis demonstrated maximal correlation coefficients at a lag of 0 min between insulin and C-peptide (control r = 0.33, P < 0.0001; Kx r = 0.17, P = 0.06) and between insulin and glucose (control r = 0.21, P < 0.001; Kx r = 0.20, P < 0.02) in the control and Kx groups, respectively, whereas no significant correlations were observed at any lag in the Px group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495810 TI - Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats. AB - Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands. PMID- 8495811 TI - Lower-extremity amputation. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study. AB - Oklahoma Indians with NIDDM (n = 1012) underwent a baseline examination in 1972 1980. The incidence of and risk factors for first lower-extremity amputation were estimated. The mortality rates of amputees using data from 875 patients who had no previous history of amputation and who underwent follow-up examination between 1987 and 1991 are presented. The mean age of the 875 patients was 51.6 +/- 10.8 yr, and the mean duration of diabetes was 6.6 +/- 6.1 yr. After a mean follow-up time of 9.9 +/- 4.3 yr, the incidence rate of first LEA among diabetic Oklahoma Indians was 18.0/1000 person-yr. The incidence rate was two times higher in men than in women. In both sexes, significant risk factors (P < 0.05) were retinopathy and duration of diabetes. Fasting plasma glucose, use of insulin, and systolic blood pressure were significant for men only. For women, plasma cholesterol and diastolic blood pressure were additional risk factors. Compared with the mortality rate of 33.5/1000 person-yr among nonamputees, the rate among amputees was 55.5/1000 person-yr. The 5-yr survival rate after first amputation was 40.4%. For the amputees, the most common causes of death were diabetes (37.3%), cardiovascular disease (29.1%), and renal disease (7.3%). The incidence and mortality rates in diabetic Oklahoma Indians were higher than those reported in Pima Indians and other diabetic populations. To lower the incidence of lower extremity amputation in this high-risk population, preventive action through education, foot care programs, and early detection of lesions must be intensified. PMID- 8495812 TI - Structure and segmental localization of glycogen in the diabetic rat kidney. AB - Pathological accumulations of glycogen were studied in the kidney tubular epithelium in untreated STZ-induced diabetic rats of 50 days diabetes duration. Blood glucose concentrations were approximately 17 mM, and the animals had no ketonuria. At the termination of the experiment, the kidneys were perfusion fixed, and serial sections were cut from the renal capsule to the tip of the papilla and stained with toluidine blue and periodic acid Schiff. By tracing tubular profiles from section to section in a light microscope, the outlines of nephrons were reconstructed, and abnormal glycogen accumulations were mapped in accordance with the outlines. The exact segmental localization, character, and extension of the glycogen accumulations were determined. The predominant location of the pathological glycogen accumulations was in the thick ascending limb of Henle's loop. Dot-shaped and diffuse-appearing glycogen accumulations were discretely distributed throughout the segment, and large confluent cytoplasmic accumulations of glycogen were also present. On a continuous basis, glycogen was present only in the cortical thick ascending limb of Henle's loop and the macula densa segment excluding the macula densa cells. In the distal convoluted tubule and the cortical collecting duct system, scattered dot-shaped and diffuse glycogen accumulations were discretely distributed. Furthermore, glycogen appeared as confluent, cytoplasmic accumulations in the initial part of the descending thin limb of Henle's loop. In addition, glycogen accumulations were found in nuclei within a narrow stripe of the outer stripe of the outer medulla in the medullary thick ascending limb of Henle's loop. PMID- 8495813 TI - Murine insulinoma cell line with normal glucose-regulated insulin secretion. AB - Pancreatic beta TC lines derived from insulinomas arising in transgenic mice expressing SV40 Tag under control of the insulin promoter manifest a differentiated beta-cell phenotype and secrete insulin in response to glucose. Previously reported beta TC lines respond to subphysiological extracellular glucose levels compared with normal beta-cells. Recently, several beta TC lines were developed with normal glucose-regulated insulin secretion from insulinomas obtained by breeding of the RIP-Tag transgene from the original C57BI/6 mouse strain into the C3HeB/FeJ strain. One of these beta TC lines, beta TC7, was characterized in detail. Beta TC7 cells express GLUT2 and have levels of glucokinase and hexokinase activity similar to those of normal islets. As a result these cells exhibit a normal glucose concentration dependency for glycolysis and insulin secretion, thus representing an accurate model of beta cell function. On continuous propagation in culture, beta TC7 cells acquired a response to lower extracellular glucose levels. This change was associated with a fourfold increase in hexokinase activity, without significant changes in glucokinase activity and glucose uptake rates. These findings suggest an important role for glucose phosphorylation rates in regulation of the beta-cell insulin secretory response to glucose. PMID- 8495814 TI - The effects of hyperinsulinemia and hyperglycemia on GLUT4 and hexokinase II mRNA and protein in rat skeletal muscle and adipose tissue. AB - The GLUT4 glucose transporter and type II hexokinase are predominantly expressed in skeletal muscle and adipose tissue. The effects of insulin and glucose on the expression of GLUT4 and HKII were studied in vivo by using the euglycemic hyperinsulinemic and hyperglycemic-hyperinsulinemic clamp methods. The clamps were maintained in conscious rats for 6 or 24 h after a 1-day starvation period. Adipose tissue GLUT4 mRNA was increased 4-fold after 6 h and 23-fold after 24 h of hyperinsulinemia; HKII mRNA was increased by four- and eightfold after 6 and 24 h, respectively. In contrast, GLUT4 mRNA was not significantly changed in skeletal muscle by either the euglycemic- or hyperglycemic-hyperinsulinemic clamps. Each of these treatments resulted in a fourfold induction of HKII mRNA. No changes of GLUT4 protein and hexokinase activity were detected after 6 h of hyperinsulinemia in either skeletal muscle or adipose tissue. After 24 h of hyperinsulinemia, adipose tissue GLUT4 protein had doubled, whereas skeletal muscle GLUT4 was unchanged. In contrast, hexokinase activity increased by two- to eightfold in skeletal muscle and adipose tissue. Hyperinsulinemia alone was sufficient to mediate the effects observed, because no additional effects were seen when hyperglycemia accompanied hyperinsulinemia. These results reveal the lack of coordinate regulation of GLUT4 and HKII in adipose tissue and skeletal muscle. Whereas hyperinsulinemia increases both GLUT4 and HKII mRNA and protein levels in adipose tissue, this treatment increases HKII mRNA and protein in skeletal muscle, but has no effect on GLUT4 in this tissue. PMID- 8495815 TI - Identification of a simple tandem repeat DNA polymorphism in the human glycogen synthase gene and linkage to five markers on chromosome 19q. AB - We have identified a simple tandem repeat DNA polymorphism in the human glycogen synthase gene of the form (TG)n. This DNA polymorphism has 10 alleles and a heterozygosity of 0.82 and can be easily typed using the polymerase chain reaction. It has been localized within the framework genetic map of chromosome 19 and is located in the region of the apolipoprotein C-II and histidine-rich calcium-binding protein genes. This DNA polymorphism will facilitate genetic studies of the role of the glycogen synthase gene in the development of insulin resistance and NIDDM. PMID- 8495816 TI - Kinetics of proinsulin conversion in human islets. AB - Islets isolated from human cadaver pancreas were pulse-labeled (10 min with [3H]leucine) and then incubated for a 180-min chase. Islets and chase medium were collected every 15 min and analyzed by reversed-phase HPLC to quantify the percentage of radioactively labeled proinsulin, conversion intermediates, and fully processed insulin. Release of proinsulin-related labeled products into the chase medium was < 10% of total. Whereas 50% of labeled proinsulin had been lost by conversion within 45 min, fully processed insulin only appeared with a half time of 100 min. This discrepancy is attributable to accumulation of radioactive conversion intermediates. Des 64.65 split proinsulin was a minor component, reaching a maximum of 5.2 +/- 1.7% (n = 4) at 60 min of chase. By contrast, des 31.32 split proinsulin--and a truncated form lacking the first three residues of C-peptide--rose progressively to 29.3 +/- 1.4% by 75 min, and declined thereafter. The accumulation of des 31.32 split proinsulin rather than the des 64.65 split form during the conversion of human proinsulin reflects slower conversion at the C-peptide/A-chain than at the B-chain/C-peptide junction, and is consistent with the appearance of this particular conversion intermediate in the circulation. PMID- 8495817 TI - Identification of glucokinase mutations in subjects with gestational diabetes mellitus. AB - Recent studies have shown that mutations in the glucokinase gene on chromosome 7 can cause an autosomal dominant form of NIDDM with a variable clinical phenotype and onset during childhood. The variable clinical phenotype includes mild fasting hyperglycemia (i.e., a plasma glucose value of > 110 mg/dl, a value that is at least 2-3 SDs above normal), impaired glucose tolerance, gestational diabetes mellitus, as well as overt NIDDM as defined using National Diabetes Data Group or World Health Organization criteria. Because gestational diabetes mellitus was a clinical feature associated with glucokinase mutations, we have screened a group of women with gestational diabetes who also had a first-degree relative with diabetes mellitus for the presence of mutations in this gene. Among 40 subjects, we identified two mutations, suggesting a prevalence of approximately 5% in this group. Extrapolating from this result, the prevalence of glucokinase-deficient NIDDM among Americans may be approximately 1 in 2500. PMID- 8495818 TI - Children's health: more than running to the doctor? PMID- 8495819 TI - Videofluoroscopy in the assessment of feeding disorders of children with neurological problems. AB - A multidisciplinary assessment, including videofluoroscopy, was carried out on 14 children with feeding difficulties associated with neurological problems. Recommendations were made on all aspects of feeding and the trunk position was changed for half of the patients. A later interview with the parents confirmed that the recommendations had been helpful. The optimum trunk position for feeding was determined during videofluoroscopy by positioning the patient in the erect or reclined position, and also by analysis of relative difficulties during the oral and pharyngeal phases of swallowing. Those with difficulties mainly in the oral phase fed best in the reclined position; those with difficulties mainly in the pharyngeal phase fed best in the erect position, particularly if they had upper oesophageal sphincter spasm in association with a tonic labyrinthine reflex. PMID- 8495820 TI - A five-year longitudinal study of thyroid function in children with Down syndrome. AB - The thyroid function and health status of 101 children with Down syndrome were assessed annually for five years. One child had congenital hypothyroidism at entry to the study. During the study period, eight more developed compensated hypothyroidism. Five of 10 children with compensated hypothyroidism still had the condition at the end of the study, it resolved spontaneously in four and one child developed uncompensated hypothyroidism. There were no significant differences in growth and development between those with compensated hypothyroidism and those with normal thyroid function. Two children developed transient rises in thyroxine, associated with elevations in thyroid-stimulating hormone (TSH). A large proportion of thyroid dysfunction in children with Down syndrome is transient and may be related to inappropriate secretion of TSH or thyroid insensitivity to TSH, rather than to auto-immune thyroiditis. PMID- 8495821 TI - Sensory disorders in cerebral palsy: two-point discrimination. AB - Two-point discrimination (TPD) was measured on eight points of the upper extremities of 220 children with cerebral palsy aged between seven and 14 years. 46 had classical diplegia, 23 had mildly spastic diplegia (without adductor spasms), 86 had hemiplegia, 26 had generalized dyskinesia, 10 had right- and four had left-sided hemiathetosis and 25 had quadriplegia. TPD was decreased in all cases compared with normal controls: slightly more for the classical forms of diplegia and on the paretic side of those with hemiplegia, slightly less in athetoid children. This adds further evidence to the authors' previous observations that sensory disorder is an integral part of the clinical picture of cerebral palsy. PMID- 8495822 TI - Changes of sagittal-plane ankle motion and ground reaction force (fore-aft shear) in normal children aged four to 10 years. AB - The authors investigated the changes in ankle-joint kinematics and ground reaction force during gait in normal children aged four to 10 years. Dorsiflexion of the ankle joint became slower and well controlled from early to mid stance phase with age. The main changes were found at about five years of age. The peak for the fore-aft shear component of the ground reaction force in the deceleration phase occurred later, and was noted during dorsiflexion. However, the peak for plantar flexion, plantar flexion angular velocity and the fore-aft shear component of ground reaction force (all seen during the acceleration phase) did not change significantly with age. These findings appear to be related to maturation of the ankle plantar flexors. PMID- 8495823 TI - Neonatal bacterial meningitis in the middle belt of Nigeria. AB - A three-year prospective study of neonatal meningitis in a tertiary hospital in Nigeria was carried out to determine its clinical spectrum and particular characteristics. The 36 infants studied represented a high incidence of 1.9 per 1000 live births, and the infection was significantly higher among low birthweight babies. Non-specific signs and symptoms were common, and temperature instability was a constant finding. Specific neurological manifestations were noted that differed from other reports in the literature and contributed significantly to outcome. The most common aetiological pathogen isolated was Gram positive Staphylococcus aureus and the most common Gram-negative organisms were Klebsiella spp: there was no case of group B streptococci. The pathogens isolated were also at variance with other reports. The mortality rate was 33 per cent and was higher for females. There was no significant difference in outcome between inborn and referred infants, nor between early onset and late onset of the disease. A bulging anterior fontanelle was a significant indicator of poor prognosis. Gentamicin and ceftazidime were the most appropriate antibiotics. PMID- 8495824 TI - Eye movement and electrophysiological findings in an infant with hemispheric pathology. AB - A visually unresponsive infant had a normal ophthalmological examination. Eye movement studies using electro-oculography revealed asymmetrical binocular smooth pursuit, binocular optokinetic nystagmus and vestibulo-ocular reflex. Electrophysiological testing showed markedly asymmetrical occipital flash and pattern visual evoked potentials. Both investigations suggested a posterior right hemispheric problem, which was confirmed with cranial ultrasound. This case study illustrates the usefulness of non-invasive techniques in neuro-ophthalmological investigations of young children. PMID- 8495825 TI - Benign paroxysmal tonic upgaze of childhood with ataxia. A neuro-ophthalmological syndrome of familial origin? AB - A new neuro-ophthalmological syndrome has been described recently, consisting of paroxysmal tonic upward deviation of the eyes with ataxia. Episodes occur daily and are always relieved by sleep. Onset is usually under one year of age and the symptoms gradually disappear during childhood. The authors describe three new patients in whom an autosomal dominant mode of inheritance was a constant finding, as well as clumsiness and delayed acquisition of independent gait. Treatment with levodopa was of clear benefit. PMID- 8495826 TI - A research definition for 'birth asphyxia'? PMID- 8495827 TI - Hereditary spastic paraplegia. A diagnostic reminder. PMID- 8495828 TI - Lycra splinting and the management of cerebral palsy. PMID- 8495829 TI - Comparison and characterization of ulcerations induced by endoscopic ligation of esophageal varices versus endoscopic sclerotherapy. AB - Esophageal variceal ligation and esophageal variceal sclerotherapy are two modes of therapy commonly used in the treatment of esophageal varices. The purpose of this study was to compare the local complications of these procedures, with special emphasis on production and healing of ulcerations. Twenty-three patients entered the study. Ten patients were randomized to esophageal variceal ligation and 13 to esophageal variceal sclerotherapy. Esophageal variceal ligation produced shallow (0.6 +/- 0.07 mm) circular ulcerations with a large surface area (85.4 +/- 20.3 mm2) that resolved in 14.4 +/- 1.4 days. Esophageal variceal sclerotherapy produced linear, deep ulcerations (1.8 +/- 0.01 mm) with a smaller surface area (13.3 +/- 2.8 mm2) and resolution in 20.9 +/- 1.3 days. These differences were statistically significant by independent t test (p < 0.0001). Esophageal variceal ligation patients required 3.6 +/- 0.4 sessions to achieve obliteration, whereas esophageal variceal sclerotherapy patients required 6.2 +/- 0.5 sessions (independent t test, p < 0.0001). No significant difference was noted between the two groups with regard to death or stricture formation. PMID- 8495830 TI - Endoscopic ligation of esophageal varices compared with injection sclerotherapy: a prospective randomized trial. AB - Fifty cirrhotic patients with esophageal varices underwent endoscopic treatment in a prospective randomized trial carried out to compare variceal ligation with injection sclerotherapy, with respect to safety, efficacy, and complications in the initial session. Twenty-five patients each were treated using endoscopic variceal ligation or endoscopic injection sclerotherapy in the initial session and then only endoscopic injection sclerotherapy for all following sessions. Ligations numbered 4.1 at the initial session. The total number of sessions of endoscopic injection sclerotherapy was 4.0 +/- 1.3 in the endoscopic injection sclerotherapy group compared with 3.6 +/- 1.4 in the endoscopic variceal ligation group. The total volume of the sclerosant used by the end of all the sessions was 23.9 +/- 10.3 ml in the endoscopic variceal ligation group and 39.0 +/- 11.5 ml in the endoscopic injection sclerotherapy group (p < 0.0001). In all patients, complete eradication of the varices was achieved, and at 7 to 15 months follow-up no evidence of recurrence was seen. Adverse effects such as pyrexia, chest pain, and pleural effusion after the initial session were significantly lower in the endoscopic variceal ligation group (p < 0.05), and total bilirubin, serum creatinine, lactate dehydrogenase, and urinary beta 2-microglobulin were significantly increased and PaO2 decreased after endoscopic injection sclerotherapy (p < 0.05). This study shows that endoscopic variceal ligation significantly decreased the adverse effects associated with endoscopic injection sclerotherapy in the initial session, and it is recommended as an alternative to sclerotherapy. PMID- 8495831 TI - Endoscopic snare excision of benign adenomas of the papilla of Vater. AB - Over a 5-year period (1985 to 1990), 25 patients (11 men and 14 women, median age 68) with adenomatous tumors of the papilla of Vater judged to be benign by endoscopic appearance and forceps biopsy were included in this study. All patients had de novo tumors except for two patients who had recurrent adenomas after local surgical excision. Presenting symptoms included pain (19 patients), jaundice (9 patients), and pancreatitis (4 patients). ERCP showed bile and pancreatic duct dilation in 20 patients (6 with stones) and 2 patients, respectively. The adenoma and the papilla of Vater were excised using a standard polypectomy snare (snare papillectomy). Procedure-related complications included bleeding in two patients and acute pancreatitis in three patients. No deaths occurred. Histologic analysis showed benign adenoma with mild to moderate dysplasia in 18 patients and severe dysplasia in 1 patient. Two patients with evidence for intraductal tumor extension on ERCP were referred for surgery. Six patients had recurrences at a median follow-up of 37 months (range, 7 to 79 months), of whom one had intraductal tumor spread and underwent pancreatoduodenectomy. Five patients were re-treated endoscopically; one ultimately required surgery. PMID- 8495832 TI - Malpractice claims in gastrointestinal endoscopy: analysis of an insurance industry data base. AB - We investigated 610 endoscopy-associated and 486 gastroenterology-associated malpractice claim files of the Physicians Insurers Association of America data sharing project. We determined the relative malpractice claim risk for each of the major types of endoscopic procedures by comparing claim frequencies with Medicare performance frequencies. Relative malpractice risks were 1.0 for sigmoidoscopy, 1.2 for esophagogastroduodenoscopy, 1.6 for endoscopic retrograde cholangiopancreatography, and 1.7 for colonoscopy. "Improper performance" was alleged in 54% of claims and "diagnosis error" in 24% of claims. Of 121 claim files alleging a diagnostic error, 74 (61%) pertained to missed malignancies, of which 69% were colorectal. Of 147 claims alleging iatrogenic injury, 140 (95%) involved perforation or similar direct injury to the gastrointestinal tract. Problems with consent were alleged in 44% of 158 endoscopy-related claim files alleging additional associated issues. PMID- 8495833 TI - Endoscopic ultrasonography in primary gastric lymphoma: correlation with endoscopic and histologic findings. AB - To evaluate the potential value of endoscopic ultrasonography in primary gastric lymphoma, we compared endoscopic ultrasonography findings with endoscopic and histologic findings in 15 patients in whom the diagnosis had been established by radiography and endoscopy, including forceps biopsy. The patients were divided into four groups according to the endoscopic ultrasonography findings. The groups included the following: superficially spreading type (six patients), diffusely infiltrating type (three patients), mass-forming type (four patients), and mixed type (two patients). The endoscopic ultrasonography findings correlated well with the endoscopic, macroscopic, and histologic findings. The histologic findings in nine patients with the endoscopic ultrasonography superficially spreading type or diffusely infiltrating type revealed B-cell lymphoma arising from mucosa associated lymphoid tissue, which shows slowly infiltrative growth. In four patients with the endoscopic ultrasonography mass-forming type, on the other hand, the tumor histologic finding consisted of diffuse large-cell or diffuse mixed-cell type. Our results indicate that endoscopic ultrasonography may provide information helpful for the management of primary gastric lymphoma. PMID- 8495834 TI - Changes in esophageal wall layers during motility: measurements with a new miniature ultrasound suction device. AB - We have developed a miniaturized ultrasound device that attaches to the gastrointestinal mucosa by suction and produces high-resolution (+/- 0.1 mm) images of the layers of the intestinal wall. The esophageal wall layers in a single sheep were measured during 20 occlusive contractions observed with simultaneous endoscopy, which revealed thickening of the inner circular muscle layer from 1.2 +/- 0.2 mm to 2.2 +/- 0.4 mm (p < 0.01), and during 20 dilations demonstrating thinning of the full thickness of the esophageal wall from 3.6 +/- 0.3 mm to 2.9 +/- 0.3 mm (p < 0.01). Safety experiments performed in two canine stomachs demonstrated no erosions or ulceration at any level of suction. Our investigations indicate that the M-mode suction ultrasound device can safely assess changes occurring in the layers of the esophageal wall during contractions and dilations and should be evaluated for the study of human intestinal motility. PMID- 8495835 TI - Endoscopic balloon dilation of esophageal strictures in children. AB - A total of 17 patients, ages 3 weeks to 14 1/2 years, had 20 esophageal strictures develop after repair of esophageal atresia (9 strictures); primary gastroesophageal reflux (3 strictures); Nissen fundoplication (4 strictures); epidermolysis bullosa congenita dystrophica (1 stricture); congenital esophageal stenosis (2 strictures); or colonic interposition (1 stricture). These strictures were treated with 132 endoscopic balloon catheter dilations (average, 6.6/patient, range, 1 to 24) during a period of 42 months (average, 8 months; range, 2 to 42 months). Fifteen of the 17 patients are now asymptomatic. Thirteen of the 17 patients had documented reflux esophagitis and were also medically treated. The two residually symptomatic patients included a patient with severe proximal esophagitis secondary to epidermolysis bullosa congenita dystrophica who had only a temporary response to dilations and another patient with a tight Nissen fundoplication who did not improve after dilation but is now asymptomatic after corrective surgery. The 10 patients with tracheoesophageal fistula repair were asymptomatic within 3 to 21 months (average, 10.8 months). Only one patient had perforation develop as a result of the procedure. Sixteen of 17 patients had the procedures performed as outpatients. All patients were given oral feedings throughout the course of dilation and had normal growth. PMID- 8495836 TI - The Cohen test does not predict outcome in achalasia after pneumatic dilation. AB - The Cohen test has been recommended to evaluate the efficacy of pneumatic dilation of the lower esophageal sphincter in patients with achalasia. It consists of ingestion of 8 ounces of heavy barium. Upright radiographs are performed 5 minutes later to determine the height of the barium column in the esophagus in relation to the diaphragm. A column less than 1 cm above the diaphragm is a negative test indicating successful dilation and the high probability of dysphagia resolution. A positive Cohen test, a column exceeding 1 cm, is said to correlate with persistent symptoms and need for redilation. We evaluated this in a prospective manner for a 6-year period. Twenty-eight patients underwent standard technique pneumatic dilation at our institution. Achalasia was confirmed in all patients by way of upper endoscopy and manometry. A Cohen test was performed in all patients. Post-dilation symptoms and weight were analyzed at follow-up 6 weeks after dilation. Contrary to the original report, relief of dysphagia after dilation was not related to the results of the Cohen test (p = 0.77). A positive Cohen test was inversely correlated with both symptom duration (0.037) and lower esophageal sphincter pressure before dilation (p = 0.005). Weight gain after dilation was unrelated to Cohen test results (p = 0.67). We conclude that the Cohen test is not an accurate predictor of symptom relief after dilation and do not recommend its use to determine the end point of therapy in patients with achalasia. PMID- 8495837 TI - The management of complicated hepatolithiasis with intrahepatic biliary stricture by the combination of T-tube tract dilation and endoscopic electrohydraulic lithotripsy. AB - Hepatolithiasis with intrahepatic biliary strictures, more common in Southeast Asia than elsewhere, remains a difficult problem to manage. Retention of stones behind strictures after surgery is a frequent and troublesome complication. Post operative duct dilation with percutaneous transhepatic cholangioscopy tube stenting through a matured T-tube tract was performed in 15 patients. Choledochoscopic electrohydraulic lithotripsy was applied in six patients when impacted or large stones were encountered. Complete clearance of stones was achieved in 12 patients (80%). Two patients had fevers develop after ductal dilation and recovered after conservative treatment. These 12 successfully treated patients remain well, with a mean follow-up of 18 months. Post-operative T-tube tract dilation, selectively combined with endoscopic electrohydraulic lithotripsy, is an effective and safe method for complicated hepatolithiasis with biliary strictures. PMID- 8495838 TI - Endoscopic closure of a perforation using metallic clips after snare excision of a gastric leiomyoma. PMID- 8495839 TI - Endoscopic nasobiliary drainage for acute suppurative cholangitis: a sonographically guided method. PMID- 8495840 TI - Laparoscopy-guided subhepatic cholecystostomy: a feasibility study in swine. PMID- 8495841 TI - Complications associated with endoscopic band ligation of esophageal varices. PMID- 8495842 TI - Complications of esophageal variceal band ligation. PMID- 8495843 TI - "Pinch" injury during overtube placement in upper endoscopy. PMID- 8495844 TI - Endoscopic ligation of bleeding rectal varices. PMID- 8495845 TI - Delayed hemobilia secondary to expandable metal stent. PMID- 8495846 TI - Collagenous colitis: an unusual endoscopic appearance. PMID- 8495847 TI - Sigmoid volvulus treated with endoscopic sigmoidopexy. PMID- 8495848 TI - Dormia basket entanglement with a T tube: management with interventional radiologic techniques. PMID- 8495849 TI - Endoscopic ligation: now and the future. PMID- 8495850 TI - Endoscopic snare papillectomy. PMID- 8495851 TI - Laser therapy of Barrett's mucosa. PMID- 8495852 TI - Appearance of duodenal folds and untreated adult celiac disease. PMID- 8495853 TI - The optimal interval for endoscopic variceal ligation with low-dose sclerotherapy. PMID- 8495854 TI - Colonic lesions in portal hypertension. PMID- 8495855 TI - Pseudopolyposis medicamentosus. PMID- 8495856 TI - Gastric mucosal disruption (fissuring) as a sign of impending perforation in a patient with gastric volvulus. PMID- 8495857 TI - Colonoscopic diagnosis of whipworm infection. PMID- 8495858 TI - Watermelon in the colon: the real thing. PMID- 8495859 TI - Impaction of a stone basket in the gallbladder with laparoscopic rescue. PMID- 8495860 TI - Vasodepressor reaction in an unsedated patient undergoing colonoscopy and observing the video display. PMID- 8495861 TI - Is there a need for long-term thromboprophylaxis following general surgery? AB - Thromboprophylaxis to surgical patients is generally accepted, and used in the perioperative period by many surgeons as effective means of reducing postoperative thromboembolic complications. Often the prophylaxis is stopped at the time of mobilization or discharge of the patient, although late thromboembolic complications after cessation of the postoperative prophylaxis are known to occur up to 7 weeks after surgery. By scrutinizing thromboprophylactic studies performed in general surgery during the last 20 years, we found the incidence of late thromboembolic complications reported to be about 1% when clinical diagnostics was applied. In studies where the patients were screened for late thromboembolic complications using paraclinical diagnostic methods the incidence is 10 times higher. The clinical relevance of these late postoperative thromboembolic complications is still uncertain, as is the value of long-term prophylaxis. PMID- 8495862 TI - Antithrombotic properties of a truncated recombinant tissue factor pathway inhibitor in an experimental venous thrombosis model. AB - The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1 161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0 10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin. PMID- 8495863 TI - The role of oxygen radicals in human disease, with particular reference to the vascular system. AB - Free radicals, such as superoxide, hydroxyl and nitric oxide, and other reactive oxygen species (ROS), such as hydrogen peroxide, are formed in vivo. Imbalance between production of ROS and anti-oxidant defence can result in oxidative stress, which may arise either from deficiencies of anti-oxidants (such as glutathione, ascorbate or alpha-tocopherol) and/or from increased formation of ROS. Oxidative stress can result in glutathione depletion, lipid peroxidation, membrane damage and DNA strand breaks as well as activation of proteases, nucleases and protein kinases. Some degree of oxidative stress occurs in most, if not all, human diseases, and the major question to be answered is whether it makes a significant contribution to the disease pathology. In the case of atherosclerosis, evidence from studies with the chain-breaking anti-oxidant probucol and from epidemiological work suggests that oxidative damage does indeed make an important contribution to plaque development. PMID- 8495864 TI - Neutrophils and deep venous thrombosis. AB - A case can be made for the participation of polymorphonuclears (PMN) in the initiation and propagation of venous thrombosis. In animal models leukocytes adhered to areas of veins that serve as sites for initiation of thrombi in patients. In addition, PMN are found in white layers of thrombin where they may interact with platelets to attract more of each. This would add bulk and promote coagulation so that red layers are formed. Lidocaine and one of its derivatives inhibited leukocyte adhesion to veins in dogs and lidocaine reduced the incidence of deep venous thrombosis (DVT) in patients after hip replacement, suggesting but not proving that inhibition of PMN adhesion might have contributed. A new approach for preventing PMN contribution to DVT is suggested by recent studies which identified three families of adhesive receptors (integrins, intercellular adhesion molecules and selectins) on endothelium, leukocytes and platelets. Monoclonal antibodies against beta 2-integrins on leukocytes reduced leukocyte adhesion, emigration and PMN-dependent tissue injury in infection, inflammation and ischemia-reperfusion injury in animals. Selectins bind to specific carbohydrate ligands containing sialylated Lewis X, suggesting that relatively small analogues might inhibit PMN adhesion. Both platelets and PMN adhere to polymerizing fibrin through undefined mechanisms. Inhibition of this process might inhibit the buildup of white layers of thrombi. PMID- 8495865 TI - Isolation and characterization of ryudocan and syndecan heparan sulfate proteoglycans, core proteins, and cDNAs from a rat endothelial cell line. AB - We have isolated heparan sulfate proteoglycans (HSPGs) from cloned rat microvascular endothelial cells using a combination of ion-exchange chromatography, affinity fractionation with antithrombin III (AT III), and gel filtration in denaturing solvents. The anticoagulantly active heparan sulfate proteoglycans (HSPGact) which bind tightly to AT III bear mainly anticoagulantly active heparan sulfate (HSact) whereas the anticoagulantly inactive heparan sulfate proteoglycans (HSPGinact) possess mainly anticoagulantly inactive heparan sulfate (HSinact). The core proteins of HSPGact and HSPGinact were isolated by treatment with Flavobacterium heparitinase and purification by ion-exchange chromatography. SDS-PAGE showed that both sets of core proteins exhibited three major components with M(r) of 25-, 30-, and 50-kD, respectively. Peptide mapping revealed that HSPGact and HSPGinact possess extremely similar core proteins. The primary sequences of internal peptides obtained from HSPGinact core proteins and the NH2-terminal sequence analyses of the 25-kD component from the HSPGinact core proteins demonstrate that the 30-kD component is a previously unidentified species--designated as ryudocan--with the 25-kD component representing a proteolytic degradation product; while the 50-kD component is the rat homolog of syndecan [Saunders S, Jalkanen M, O'Farrell S, Bernfield M: J Cell Biol 1989; 108:1547-1556]. Specific oligonucleotide probes were obtained for ryudocan and syndecan by PCR, and the corresponding cDNAs were isolated from a RFP-EC library. The cDNAs encode type I integral membrane proteins of 202 and 313 amino acids, respectively, which have homologous transmembrane and intracellular domains but very distinct extracellular regions. In particular, ryudocan exhibits only 3 potential glycosaminoglycan (GAG) attachment sites within the extracellular region while syndecan has 5 GAG attachment sites within the same domain. The levels of ryudocan and syndecan mRNA were measured by quantitative PCR in primary microvascular endothelial cells and associated non-endothelial cells isolated by cell sorting. Ryudocan and syndecan mRNAs were abundantly expressed in both populations representing about 0.1-0.5% of mRNA. PMID- 8495866 TI - Mechanisms of inhibition by heparin of vascular smooth muscle cell proliferation and migration. AB - Heparin, an inhibitor of vascular smooth muscle cell proliferation and migration, affects a number of other cell functions. These effects include inhibition of growth factor binding, deposition of matrix proteins and gene expression. Various mechanisms have been proposed and, yet, how heparin works as an inhibitor remains unclear. We have postulated that heparin inhibits smooth muscle cell growth and migration by suppressing the expression of matrix-degrading enzymes such as plasminogen activators and interstitial collagenase. The molecular mechanism of heparin's inhibitory action on these proteases is currently under investigation. PMID- 8495867 TI - Modulation of vascular antithrombin III in human cardiac allografts. AB - The natural anticoagulant pathway involving heparan sulfate proteoglycan and antithrombin III (ATIII) was studied in serial biopsies from 90 cardiac allograft recipients. The ATIII component of this pathway was identified immunocytochemically on venous endothelium and arterial smooth muscle cells and intima of normal donor hearts and stable allografts. Unstable grafts lacked vascular ATIII and contained fibrin deposits. Neither stable nor unstable grafts had ATIII-reactive capillary endothelium. Grafts with absent vascular ATIII could (1) result in death, (2) revert to an arterial/venous ATIII distribution or (3) develop ATIII-reactive capillary endothelium. The development of ATIII-reactive capillaries was associated with a survival advantage, and such reactivity seemed to be promoted by heparin. PMID- 8495868 TI - Heparin and pregnancy in women with a history of repeated miscarriages. AB - Many patients who experience recurrent spontaneous abortions (RSA) have high titered antibodies to trophoblast antigens and/or negatively charged phospholipids. Pregnancy success has been documented in some of these patients subsequent to heparin treatment. The effect of heparin on in vitro assays used to detect antibodies to phospholipids and trophoblast antigens has been investigated. We have found that complement-mediated detection of antibodies to trophoblast and lymphocyte antigens is inhibited by absorption of sera with solid phase heparin. The data show that such inhibition involves an inhibitor and a heparin-sensitive regulator of the inhibitor. Heparin inhibits binding of antiphospholipid antibodies to phospholipids in solid-phase ELISA. The mechanism for this inhibition appears to involve an interaction between heparin and antibody to phospholipid. These findings reveal novel heparin-mediated reactions that bridge immunological and hematological interactions. The extent of heparin modulation of these antibody reactivities should be clarified in future clinical trials involving heparin treatment for RSA. PMID- 8495869 TI - Diagnostic strategies in acute pulmonary embolism. AB - A firm diagnosis of pulmonary embolism (PE) to prevent over- or undertreatment requires an integrated use of ventilation-perfusion lung scintigraphy (V/Q scan), a recent chest X-ray, bilateral selective pulmonary angiography and venous studies. The V/Q scan should be reported in terms of probabilities according to defined criteria and be combined with clinical probabilities before a treatment decision is made. A negative V/Q scan, a low-probability scan combined with low clinical suspicion or a high-probability scan with a high clinical suspicion is generally conclusive. Patients with intermediate (indeterminate) scan probability or with discordant scintigraphic clinical probability need further work-up with pulmonary angiogram or venous studies. If neither scintigraphy nor pulmonary angiography is available, accurate venous studies of the lower legs may guide treatment decision in patients suspected of having PE. We need more research to define if all patients with PE but only a minor or no clot burden proven by venous studies really need treatment. PMID- 8495870 TI - Long-term oral anticoagulant therapy for coronary artery disease. AB - The findings of recent clinical trials have led to renewed interest in the role of oral anticoagulant therapy in patients with coronary artery disease. However, there are currently two major limitations to the routine use of oral anticoagulant therapy. The first is the need for laboratory monitoring and dose adjustment. This limitation may be overcome if fixed low doses of warfarin (e.g. 1 mg/day), which have antithrombotic effects, are shown by clinical trials to be effective and safe. A second limitation to oral anticoagulant therapy is uncertainty about its effectiveness and safety compared to aspirin, or in combination with aspirin. The current pathophysiologic knowledge and recent clinical trial data provide support for further clinical trials evaluating combined warfarin and aspirin treatment in the long-term care of patients with coronary artery disease, and in the primary prevention of myocardial infarction. PMID- 8495871 TI - Thromboprophylaxis in emergency surgery. AB - Except for hip fracture surgery, emergency surgery has been only exceptionally studied concerning thromboprophylaxis. There are, however, several reasons to believe the frequency to be fairly high and that the patient group would be in need of prophylaxis. This paper discusses various emergency situations and also gives the design for an ongoing controlled study on the effect of postoperative start of thromboprophylaxis with low molecular weight heparin in emergency abdominal surgery. PMID- 8495872 TI - Screening and diagnosis of deep vein thrombosis and pulmonary embolism. AB - Clinical diagnosis of deep vein thrombosis and pulmonary embolism is difficult. Therefore objective tests are necessary. This paper discusses the principal viewpoints on which criteria can be used for various tests and how new methods should be evaluated. PMID- 8495873 TI - Venous duplex imaging for the diagnosis of acute deep venous thrombosis. AB - Acute deep venous thrombosis (DVT) continues to be a common clinical problem requiring objective evaluation. Hemodynamic testing for acute DVT has been popular, but is inadequate for evaluating asymptomatic patients and symptomatic patients with isolated calf vein thrombi. Venous duplex imaging (VDI) has rapidly gained in popularity, and is generally accepted to be the noninvasive technique of choice for the evaluation of patients with acute DVT. Twenty-five reports evaluate gray-scale venous duplex imaging versus ascending phlebography in 2,781 symptomatic patients. The sensitivity for proximal DVT and calf DVT is 96 and 80%, respectively. Seven reports review the use of VDI for surveillance in 857 asymptomatic patients, with an overall sensitivity of 76% for proximal DVT and of 11% for isolated calf vein thrombosis. The results of color-flow duplex appear to be somewhat better; however, the numbers are considerably smaller. The results for identification of calf vein thrombosis in asymptomatic surveillance patients continue to be poor. VDI appears to be the best noninvasive diagnostic test for acute DVT, and may challenge ascending phlebography as the best diagnostic test for proximal DVT in symptomatic patients, although it will miss 20% of isolated calf DVT. VDI appears to be the best noninvasive screening technique for high risk asymptomatic patients under surveillance; however, additional correlative studies with ascending phlebography are required. The addition of color Doppler images appears to have improved results, although these higher sensitivities may be the consequence of improved experience as much as the addition of color to the image. PMID- 8495874 TI - Duplex scanning in post-operative surgical patients. AB - The technique of duplex scanning for the diagnosis of deep venous thrombosis (DVT) has been developed in 3 stages. Initially B-mode imaging with compression was used. Subsequently interrogation of the venous lumen using the Doppler facility was introduced and finally the latter became simple and efficient with the introduction of colour flow imaging. Sensitivities and specificities in excess of 90% have been produced for thrombosis proximal to the calf by all methods in symptomatic patients. Colour flow imaging has given the best results for calf DVT in symptomatic patients with 86% sensitivity and 91% specificity. Before the introduction of colour flow imaging the accuracy for the detection of old thrombi in asymptomatic patients was poor. With the introduction of colour, sensitivities and specificities in excess of 90% have been obtained for proximal DVT; for calf DVT, sensitivity of 79% and specificity of 97% have been reported by 2 studies. If further studies substantiate these recent results duplex scanning will become the non-invasive method to be used in screening asymptomatic patients. PMID- 8495875 TI - Comments on reason for conflicting results of venography. AB - Conflicting results of phlebography in the diagnosis of thrombosis in different investigations are discussed. The following factors may explain different results: phlebography is a subjective method, not based on measurable parameters; insufficient phlebographic technique may result in unsafe diagnosis; the selection of patient material may vary in different investigations; variations in thrombosis incidence may vary with the age of the patient and with the season; the incidence of thrombosis varies within the postoperative period. PMID- 8495876 TI - [Primary care consultation rates among the middle aged and elderly]. AB - The consultation rate among family physicians has been widely discussed in the literature, but very few studies have been done in Israel. We analyzed the pattern of visits to the family physician of 1,860 patients aged 40 years and older in 3 urban clinics, 2 kibbutzim and 1 rural clinic with a total population of 6,700. The consultation rate rose steadily with age. It was 3.4 per year at age 40-49, and 5.6 at ages 70 and over, with a mean annual rate of 4.6. 77% of the screened population consulted the physician in 1 year and 91.4% in 3 years. Only 9.6% did not visit their physicians in the 3 years. About two-thirds visited the physician 1-4 times a year, and only 2% visited more than 15 times. In urban practices women attended more often than men but there was no significant sex difference in the rural practices. As a result of the greater visit rates of the elderly, they consumed a larger share of medical services. The mean consultation rate in this survey is similar to that in England and in other Western countries. However, it is relatively low in comparison to other studies in Israel. This may be due to the different practice setting and the use of a different sampling frame. PMID- 8495877 TI - [Intracranial complications of otorhinologic infections]. AB - In 70 patients with initial otorhinological infections there were 87 different central nervous system (CNS) complications. 40 (57%) were children (from 1 month to 15 years). 15 (21%) had more than 1 complication. Mortality was 14% (10/70). Leptomeningitis was the most common CNS complication (43%) and it occurred mainly in the pediatric age group. Lateral sinus thrombosis (LST) was accompanied by other intracranial infections in 80% of the patients. The highest mortality was found in patients with brain abscess (38%) as the initial or concomitant complication. Despite liberal use of antibiotics, CNS complications of otorhinologic infections are still encountered with considerable mortality rates. Modern imaging techniques are of great value in localizing the intracranial disease, but a complete initial otorhinologic examination is needed to rule out an extracranial focus of infection, sometimes with an insidious course. PMID- 8495878 TI - [C-reactive protein as a marker of infection in women with preterm delivery]. AB - There is a strong association between systemic and intrauterine infection and preterm delivery. C-reactive protein (CRP) is considered a nonspecific marker for intrauterine inflammation. We determined its blood level in 100 women who presented with preterm labor and intact membranes and delivered prematurely. CRP levels were used as a noninvasive marker for infection to compare clinical characteristics between women who delivered prematurely at 31-36 and 24-30 weeks of gestation. Women who delivered earlier than the 24th week of gestation had a higher rate of positive CRP levels than those who delivered later, 54% vs 24%, respectively (p < 0.0001). Moreover, women from the lower gestational age group with positive CRP levels had significantly different clinical characteristics than those in the same group but with negative CRP levels. There was a significant difference between Jewish and Bedouin women in cervical dilatation and time interval from hospitalization to delivery between those with positive CRP and those with negative CRP levels. We conclude that patients who delivered prematurely at 24-30 weeks had higher rates of an inflammatory etiology than women who also delivered prematurely, but at a more advanced gestational age. PMID- 8495879 TI - [Trimethylaminuria: fish-odor syndrome]. AB - Fish-odor syndrome is due to a rare metabolic defect in which there is massive excretion of the volatile tertiary amine, trimethylamine (TMA) in the urine. The typical fish-like odor of TMA also appears on the breath or in the sweat of affected individuals. In normal man TMA is oxidized to its odorless N-oxide derivative. TMA is of dietary origin, formed by intestinal bacterial degradation of the choline in egg yolk, liver, soybeans, etc., or by reduction of TMA-oxide present in high concentrations in marine fish. 2 sisters with the tentative diagnosis of trimethylaminuria are presented. PMID- 8495880 TI - [Thumb reconstruction with microsurgical wrap-around neurovascular flap from big toe]. AB - A 27-year-old man had his right dominant thumb amputated, together with skin from the dorsal area of the first metacarpal. Reconstruction was performed using a neurovascular flap taken from his right big toe. It consisted of skin and two thirds of the distal phalanx, including the nail bed and digital plantar nerves. The vascular pedicle of the flap was formed by branches of the dorsalis pedis artery and the greater saphenous vein. The flap was wrapped around a bony scaffold formed by an iliac bone graft and inserted into the thumb. The revascularization of the flap was performed by connecting the end of the dorsalis pedis artery to the side of the radial artery, and the end of the greater saphenous vein to the end of cephalic vein. Reinnervation was achieved by connecting the plantar digital nerves to the stumps of the digital nerves of the thumb. 1 year later, the patient expressed full satisfaction with the appearance and good function of his reconstructed thumb. PMID- 8495881 TI - [Implantation of a "pan-cameral" intraocular lens in Africa]. AB - In modern medicine, extraction of the cataractous lens is followed by implantation of an artificial intraocular lens. The 2 main types of intraocular lenses, the anterior and the posterior chamber types, are essentially different in design. We present here 11 cases in which, due to lack of facilities, we were compelled to implant posterior chamber intraocular lenses in the anterior chamber of the eye. Postoperatively, visual acuity improved in 82% of the operated eyes. PMID- 8495882 TI - [The antiphospholipid syndrome and myocardial infarction in young people]. PMID- 8495883 TI - [Air travel of patients with respiratory disease]. PMID- 8495884 TI - [Risk of HIV infection among health care workers]. PMID- 8495885 TI - [Current management of pancreatic pseudocysts]. PMID- 8495886 TI - [Influence of the psychosocial status of the elderly on surgical risks]. PMID- 8495887 TI - [When should thyroid radioisotope scanning be use in the evaluation of a suspicious thyroid nodule?]. PMID- 8495888 TI - [Muscle dystrophy and physical activity]. PMID- 8495889 TI - [Treatment of lymphedema]. PMID- 8495890 TI - [Self-measurement of blood pressure]. PMID- 8495891 TI - [Unusual tachycardia]. PMID- 8495892 TI - [Influence of interleukin-1 on intercellular communication, hematopoiesis and regulation of coronary blood flow]. PMID- 8495893 TI - [Long-term weight changes after Roux-en-Y gastric bypass for morbid obesity]. AB - 100 patients were followed for 6-9 years after Roux-en-Y gastric bypass for morbid obesity. They were randomly selected from 600 patients operated on between 1980-85. Their initial weight averaged 118 +/- 16 kg, which was 196 +/- 25% of their ideal body weight. They reached their lowest weight during an average of 15.5 months after surgery, at which time 37% were at their ideal weight, 42% were 110-130% of their ideal weight and 21% were 131-192% of their ideal weight. 90% had lost more than 50% of their excess weight. 24% had lost all their excess weight or even more, which could jeopardize nutritional status. Longer follow-up of 6-9 years showed weight gain, with 24% having become morbidly obese again, 74% having lost more than 50% of their excess weight and only 7% having lost all their excess weight. We conclude that Roux-en-Y gastric bypass induces long term weight loss and largely prevents return of morbid obesity, as long as 6-9 years after surgery. PMID- 8495894 TI - [Laparoscopic cholecystectomy]. AB - 80 patients underwent laparoscopic cholecystectomy, of whom 64 were females and 16 males (age range 20-70 years) and 15 had undergone previous abdominal operations. 3 of the 80 operations were converted to open cholecystectomy. In 11, preoperative ERCP was performed, in 2 of whom common bile duct stones were detected. In 7 intraoperative cholangiography was performed. The average hospital stay was 2.2 days. Based on this and other studies, laparoscopic cholecystectomy seems to be the operation of choice for symptomatic cholelithiasis. PMID- 8495895 TI - [Subtotal cholecystectomy: an emergency procedure for the difficult gallbladder and high-risk patient]. AB - Emergency cholecystectomy in high-risk patients is still associated with significant morbidity and mortality. Occasionally technical difficulties and bleeding diathesis are complicating factors. Our prospective experience with subtotal cholecystectomy in 23 consecutive patients is presented. All presented as increased surgical risks (APACHE II above 10) and suffered from acute cholecystitis with empyema or perforation. 1 patient died (4.4%), but overall, surgical complications were minimal. We conclude that subtotal cholecystectomy combines the advantages of cholecystectomy and cholecystostomy. We believe that this short, simple and safe procedure is a logical choice for emergency situations in critically ill patients. PMID- 8495896 TI - [Chest pain and anxiety-panic disorders in a primary care clinic]. AB - Chest pain is one of the most common complaints in primary care clinics. About 10 30% of patients with chest pain diagnosed as suffering from angina pectoris have normal coronary angiograms. Some of them suffer from psychiatric disorders. We present a 47-year-old man with several risk factors for ischemic heart disease: smoker in the past, obesity, hyperlipidemia and family history of coronary disease. He had complaints typical of anginal syndrome and normal coronary arteriograms. After 1.5 years of unsuccessful medical treatment, he was referred to the psychiatrist in the primary care clinic who diagnosed anxiety and panic disorders with somatization. All cardiac drugs were stopped and psychopharmacological treatment and psychotherapy were started immediately. Within a month he was almost free of symptoms and was treated successfully for a year. Treatment was then stopped and he has remained symptom-free for the past 4 years. We conclude that in such atypical somatic cases, only the collaboration of general practitioner and psychiatrist will lead to quick diagnosis and successful treatment. PMID- 8495897 TI - [Huntington's disease: ethical aspects of presymptomatic testing]. AB - Huntington's disease is an autosomal dominant entity with onset mostly in middle age. Neurological signs and psychosis evolve without possibility of treatment or alleviation. Genetic counseling of relatives of patients has changed since the development of presymptomatic testing. Ethical issues and dilemmas associated with the application of this technological advance are reviewed as a result of a request by a mother to perform presymptomatic testing in her young daughter whose father has Huntington's disease. PMID- 8495898 TI - [Pityriasis rosea-like eruption after anti-inflammatory and antipyretic medication]. AB - We report 2 cases of a pityriasis rosea-like eruption after the use of the anti inflammatory and antipyretic medications naproxen, acetaminophen, and a combination of acetylsalicylic acid and codeine phosphate. The role of these drugs in the induction of the eruption was supported by the results of macrophage migration inhibition factor and mast cell degranulation tests performed on the offending drugs. PMID- 8495899 TI - [Treatment of gram-negative folliculitis with isotretinoin]. AB - Gram-negative folliculitis is one of the complications of antibiotic treatment of acne. Isotretinoin is recognized as extremely effective for this condition. We describe 2 patients with gram-negative folliculitis following antibiotic treatment for acne who improved after 3-months of treatment with isotretinoin. PMID- 8495900 TI - [Screening for carriers of cystic fibrosis mutations in Ashkenazi volunteers]. AB - 309 DNA samples obtained from healthy volunteers were tested for the cystic fibrosis mutations DF508 and W1282X. 14 carriers were identified, 7 of each mutation. Since the 2 mutations account for only 80% of CF mutations, the actual number of carriers is 1 in 18. In spite of the fact that this is only a pilot study, the results suggest that screening for CF carriers is feasible and that it identifies unambiguously those who carry the CF genes. When testing for CF carriers becomes available for the general public, it will undoubtedly contribute in reducing significantly the incidence of children born with the disease. PMID- 8495901 TI - [Polymyositis and anti Jo-1 antibodies]. PMID- 8495902 TI - [Rehabilitation medicine in Israel, toward the year 2000]. PMID- 8495903 TI - [Infantile colic syndrome]. PMID- 8495904 TI - [Duodenal ulcer disease--a new etiological theory]. PMID- 8495905 TI - [Veno-occlusive disease of the liver]. PMID- 8495906 TI - [Vaginal delivery following two or more caesarean sections]. PMID- 8495907 TI - [Hemolytic uremic syndrome]. PMID- 8495908 TI - [The importance of lipocortin in the mechanism of steroid action]. PMID- 8495909 TI - [Tachycardia]. PMID- 8495910 TI - [Consanguineous marriages: demographic and medical aspects]. PMID- 8495911 TI - [Antibiotics in abdominal surgery]. PMID- 8495912 TI - [Diagnosis of late onset congenital adrenal hyperplasia]. AB - Late onset congenital adrenal hyperplasia (LOCAH) is the most common autosomal recessive disorder in the human. The incidence among women suffering from hirsutism and menstrual disorders varies from 1-35%. 21-hydroxylase deficiency is the most common variant of LOCAH. The partial enzymatic defect can be diagnosed only by ACTH stimulation tests, and not from clinical features or basal hormone levels. A variety of methods have been proposed to detect those with deficient 21 hydroxylase activity, all based on measuring steroid precursors above the enzymatic block, before and after ACTH stimulation. In this review we summarize the different methods of diagnosing 21-OH-LOCAH, and compare the incidence of this disturbance in 64 patients with hirsutism and acne, as calculated by the different methods. These 64 young women were examined in our outpatient clinic in the past 5 years, and have undergone ACTH stimulation tests. While an incidence of 5-6% of homozygote 21-OH-LOCAH was found, the incidence of the calculated heterozygote 21-OH-LOCAH varied between 16-48%. The difficulty in diagnosing heterozygote 21-OH-LOCAH is discussed. PMID- 8495913 TI - [Total colectomy and mucosal proctectomy with J-pouch anal anastomosis for ulcerative colitis and familial colonic polyposis]. AB - Total colectomy and mucosal proctectomy with ileal pouch-anal anastomosis is the accepted surgical procedure for ulcerative colitis and familial polyposis of the colon. During 1981-1990, 25 patients with ulcerative colitis or familial polyposis underwent this operation in our department. In the majority a J-pouch was performed. In the early years, an 8 cm rectal muscular sleeve was left. In later cases, in accordance with opinions expressed in the medical literature, the length of the sleeve was shortened to about 3 cm. We present the functional results and the early and late complications on follow-up of up to 10 years (mean 3.5 years). Although this operation is not the ideal solution, it is better than the alternatives and is the surgical procedure of choice. PMID- 8495914 TI - [Cost-effectiveness of disposable diapers versus catheters in dependent patients]. AB - Disposable diapers for incontinent elderly patients are expensive. Cost effectiveness analysis in this prospective study showed that diapers reduced prevalence of urinary tract infections and of infected pressure sores. The saving resulting from this reduction in morbidity lowers the cost of diapers by 40% per month. This advantage, and especially improvement in the patients' health, hygiene and quality of life, justify the use of disposable diapers. Catheters were used mostly in patients in a vegetative state, while diapers were used in the preceding stages. PMID- 8495915 TI - [Update of experience with prostatic cancer]. AB - A retrospective analysis of 302 patients with prostatic cancer, referred between 1977-1982, was updated. 15 patients (5%) with Stage A1 disease did not receive any specific treatment, and their 10-year actuarial survival was 77%. 22 (7%) had Stage A2 disease at diagnosis, 82 (27%) Stage B, 88 (29%) Stage C, and 95 (32%) Stage D. Their 10-year actuarial survival rates were 75%, 56%, 38%, and 2%, respectively. The 10-year actuarial survival of patients with well- and moderately well-differentiated adenocarcinoma was 61%, but only 13% in those with poorly differentiated adenocarcinoma (p < 0.001). A total of 116 patients with Stages A2, B and C were treated by irradiation and 71 of them also received prophylactic hormone therapy. The 10-year actuarial survival of those treated by combined irradiation and hormone therapy was 59%, compared to 19% for those treated by irradiation alone (p < 0.02). Our results emphasize the need for early diagnosis of prostatic cancer, using modern diagnostic tools such as transrectal ultrasonography and determination of prostatic specific antigen. They also prove that radiotherapy is effective and curative in a high percentage of patients with disease confined to the pelvis. PMID- 8495916 TI - [Accuracy of blood glucose measured in the hospital]. AB - Glucometer determination of capillary blood sugar (CBS) has replaced determination of glucose in the urine and in venous blood for monitoring and treating inpatient diabetics. CBS determinations were performed by 49 ward nurses chosen at random. Each performed 2 CBS measurements using an Ames Glucometer; glucose levels were also determined using a glucose-analyzer in blood obtained from the same finger puncture. Accuracy of technique was evaluated on a scale of 1 (inaccurate) to 5 (accurate) by the hospital diabetes nurse and a questionnaire was completed. A deviation of < 20% between Glucometer and glucose-analyzer results was considered satisfactory. 58% of nurses deviated by 20% or more. There was no significant correlation between accuracy of measurement and the nurse's age, seniority, department, source of instruction or number of weekly determinations. 71% of non-registered nurses and 45% of registered nurses tested inaccurately. There was a significant correlation between performance score given by the diabetes nurse and accuracy of measurement. We therefore conclude that the inaccuracy of Glucometer measurements by ward nurses is significant, registered nurses need to be trained and certified periodically in Glucometer use, an ongoing quality assurance program must be instituted on the wards, and "user friendly" Glucometers are not suitable for ward use. PMID- 8495917 TI - [Recurrent spontaneous jejunal perforation]. AB - A 70-year-old woman had recurrent spontaneous perforations of the jejunum. The first perforation, located 40 cm distal to the ligament of Treitz, was treated by debridement and suture closure. The second perforation, 2 months later, was located 20 cm distal to the first perforation and was treated by resection and primary anastomosis. On both occasions the postoperative course was uneventful and at follow-up 4 years later there were no gastrointestinal complaints. The resected specimen revealed a thinner-than-normal muscularis propria, most probably of congenital origin. PMID- 8495918 TI - [Leukocyte alkaline phosphatase: a marker for metastatic cancer]. PMID- 8495919 TI - [Inhibition of cellular uptake of low-density lipoprotein by mouse peritoneal macrophages that were pre-exposed in vivo to platelet secretory products]. PMID- 8495920 TI - [The role of combined therapy by insulin and hypoglycemic drugs in diabetes]. PMID- 8495921 TI - [Delivery room management of meconium-stained neonate]. PMID- 8495922 TI - [Practical pharmacological approach to pain control in advanced cancer]. PMID- 8495923 TI - [Nipple discharge]. PMID- 8495924 TI - [Effects of weather on rheumatic diseases]. PMID- 8495925 TI - [Rheumatoid nodulosis]. PMID- 8495927 TI - [Involvement of doctors in death penalty and in torture]. PMID- 8495926 TI - [Results of examinations for internship 1988-1991]. PMID- 8495928 TI - [Fever, tonsillitis, lymphadenopathy, hepatomegaly and splenic rupture]. PMID- 8495929 TI - [Health profile of children without medical insurance]. AB - Lack of medical insurance is a health risk factor. Underutilization or postponement of medical services, as well as lack of planning for long-term care are common among the uninsured, project was implemented within the framework of the Or Yehuda Intervention Program to assess the health status of children from birth to 17 years of age in 72 families without health insurance. Information on medical status and service utilization was summarized for 169 of the 217 children in these families. These families constituted a substantial burden on the health system, both in the form of hospitalization debt (636 hospital-days owed to a nearby hospital) and as uncompensated primary care clinic visits. Half of the visits were made by 12% of the children, while a quarter of the study children had not visited the clinic at all during the preceding year. Among families uninsured for over 2 years, the trend of underutilization was even more pronounced. Significant morbidity and signs of neglect were found among the study children, nearly 60% of whom suffered from health problems and a similar proportion had been hospitalized. The most common diagnoses were infections, congenital anomalies, and musculoskeletal and hematological problems; a third of the children had 2 or more conditions. Over 40% of the study children were referred for specialist consultation or treatment--about half of them to the pediatric subspecialties and the other half to surgical clinics. Signs of medical neglect were noted in 42.6% of study children and among 60.4% of those with 2 or more medical problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495930 TI - [Treatment of erectile dysfunction with vacuum constriction device]. AB - The vacuum constriction device (VCD) is a noninvasive mechanical device which may produce an erection by creating a vacuum of up to 250 mm Hg and with a rubber ring to maintain this state by constricting the base of the penis. We tested the VCD on 150 men who presented with organic and psychogenic impotence in our outpatient clinic between the years 1986 and 1992. Of the 150 men, 113 (75%) achieved an adequate erection with the VCD. However, only 72 patients agreed to buy the device and use it regularly. During follow-up of from 3 months to 5 1/2 years (mean 25 months), 65 men were using the VCD regularly and reported satisfying intercourse at least once every 2 weeks. Complications were minimal and consisted of mild numbness of the penis in 7 patients, mild cyanosis in 17, and 10 cases of painless ecchymoses and petechiae which disappeared without any treatment. From our experience, the VCD appears to be a safe, inexpensive, and easy method for impotent men to engage in sexual intercourse without, of course, eliminating other therapeutic options, including surgery. PMID- 8495931 TI - [An autonomous primary care clinic within a health maintenance organization]. AB - The health system in Israel, as elsewhere in the world, is facing crises of organization and economics. Israel's largest HMO, which insures some 70% of the population, is a highly centralized body that makes policy decisions without consulting the community-based primary care teams. We describe the process of extending autonomy to a primary care clinic with the object of lowering costs and allowing its staff to prioritize the problems of the patient population and the community they serve. PMID- 8495932 TI - [Temporal artery biopsy--required or superfluous?]. AB - Temporal arteritis is a systemic disease affecting large and medium-sized arteries in the elderly. The incidence of the disease increases with age and its major complications are blindness, cerebrovascular accidents and aortic dissection. Diagnosis is mainly based on clinical signs and symptoms. Temporal artery biopsy is a popular and simple diagnostic procedure and if positive confirms the diagnosis. However, a negative biopsy cannot exclude temporal arteritis due to its segmental nature, and the specific signs and symptoms still require treatment with corticosteroids. During the years 1982-1991 we performed 206 temporal artery biopsies, of which only 21 (10.2%) confirmed the presence of temporal arteritis. Our experience is presented with regard to the usefulness of temporal artery biopsy in particular. In view of the low biopsy yield we recommend more selective referral for this purpose. PMID- 8495933 TI - [Upper airway obstruction--a rare complication after anti-coagulant therapy]. AB - A case of progressive, spontaneous, nontraumatic hemorrhage into the tonsil, soft palate, hypopharynx, and larynx in a patient receiving oral anticoagulants is presented. There was no evidence of bleeding into other parts of the body. The presenting symptoms of sore-throat, dysphagia and hoarseness were mild at the time of admission. However, the bleeding later caused upper airway obstruction and aspiration, and the clinical picture during hospitalization became dramatic and life-threatening. Physicians should be aware of such possible complications in anticoagulant-treated patients, and if a hematoma is found in the pharynx or larynx the patient should be admitted for close observation and treatment. To the best of our knowledge this is the first reported case of spontaneous hemorrhage into the tonsil in a patient on oral anticoagulation. PMID- 8495934 TI - [Ring-valve abscess--a diagnostic challenge]. AB - Infective endocarditis is a life-threatening disease which may be complicated by ring-valve abscess. Since this complication increases morbidity and mortality early diagnosis is important. Pericardial effusion complicating infective endocarditis is uncommon and should raise suspicion of the presence of an abscess. We describe 2 patients admitted for infective endocarditis and pericarditis. In both, ring-valve abscess was suspected on clinical grounds. At surgery there was pathological confirmation of the diagnosis. Both patients underwent successful aortic valve replacement with complete recovery. Controlled trials are providing increasing evidence for the superiority of transesophageal echocardiography in detecting valvular vegetations. Moreover, it is the most accurate means of detecting ring-valve abscess in cases of infective endocarditis. In view of these advantages, we propose the use of transesophageal echocardiography in every case of infective endocarditis. PMID- 8495935 TI - [Isolated iliac aneurysm]. AB - The incidence of isolated iliac artery aneurysm is 1-2% of that of abdominal aortic aneurysms. The natural history is of gradual enlargement, with rupture the most common clinical presentation. The signs and symptoms of such an aneurysm are influenced by its concealed location within the bony pelvis. Awareness of these special characteristics improves the chances of early diagnosis and proper surgical treatment before possible rupture. We report 2 cases which demonstrate the spectrum of the clinical presentation. PMID- 8495936 TI - [Monocular blindness following blunt head trauma]. AB - An uncommon, devastating complication of blunt head trauma is monocular blindness. We present a 40-year-old man who complained of visual loss in the right eye a few days after minor closed head trauma. Electrophysiologic study (VEP) proved severe damage to the right optic nerve, most probably due to transection of the nerve. Based on the assumption that optic nerve injury might be analogous to spinal cord injury, we used methylprednisolone: a loading dose of 30 mg/kg was followed 2 hours later by 15 mg/kg, which was then given every 6 hours for 48 hours. Surgical decompression of the bony optic canal was not performed. There are no good data to guide our decision-making. A prospective randomized trial is required to provide definitive management guidelines in this severe and dramatic injury. PMID- 8495937 TI - [Genetic aspects of immunological processes in multiple sclerosis]. PMID- 8495938 TI - [Intratracheal pulmonary ventilation]. PMID- 8495939 TI - [Trichotillomania--hair-pulling mania]. PMID- 8495940 TI - [Hip fracture in the elderly--"beyond the metal work"]. PMID- 8495941 TI - [Functional, neurological and surgical aspects of the tetraplegic's hand]. PMID- 8495942 TI - [Bone necrosis following corticosteroid therapy]. PMID- 8495943 TI - [Rheumatoid arthritis in the elderly: diagnostic and therapeutic aspects]. PMID- 8495944 TI - [Sunglasses for children as public health measure]. PMID- 8495945 TI - [Prof. Felix Mandl (1892-1957)--a forgotten giant]. PMID- 8495946 TI - [Endocarditis with negative blood cultures]. PMID- 8495947 TI - [3-dimensional imaging diagnosis with a personal computer]. AB - During orthodontic and surgical treatment planning of severe dentofacial deformities, 3D-reconstruction imaging from axial CT-scans could previously only be handled by high-capacity computers in radiological centers. The improved performance of personal computers enables CT-scan data be transferred to a standardized MS-DOS computer. The presented software displays a 3D-reconstruction and secondary reformed vertical slices within seconds on the monitor. The symmetry of the 3D-objects can be evaluated with a freely definable grid. The distance between two different landmarks in the 3D-image can also be measured. Various tools for data manipulation permit surgical treatment simulation. The advantage of 3D-imaging with a personal computer is the user-specified orientation of the software. The off-line computing system permits a high degree of flexibility independent of any computing center. PMID- 8495948 TI - [Enamel damage depending on the method of bracket removal]. AB - Two different methods of removing brackets, on the one side by torsion and on the other by bending, were compared for the purpose of analyzing the respective enamel lesions. Each test group consisted of 19 extracted human molars with metal brackets attached to the molars by means of the "concise etching technique". Bracket removal was standardized through the use of a Wolpert "Universalprufmaschine TZZ 707" with modified torsion and bending mechanism. A scanning electron microscope was used to analyze the enamel surface. When using the torsion method, the mean extension of the enamel lesions was 48.3% of the adhesive free enamel surface. These lesions often reached into the deeper enamel layers and were mainly to be found on the broad side of the bonded area. On the other hand, when using the bending method, the enamel lesions were less frequent. They were mainly superficial and were confined almost exclusively to the pressure zones. The stress required to remove the brackets and the stress distribution were calculated on mechanical models and these results corresponded well with the enamel lesions observed on the molars. It can thus be concluded that the method of removing brackets is clinically relevant in relation to enamel lesions. PMID- 8495949 TI - [The materials properties of the stock for positioners--an in-vitro study. I. The elastic behavior]. AB - The purpose of this study was to compare the physical and mechanical properties of materials for tooth positioners. 15 of these materials are in general use and four are experimental. Tensile strength at 20% elongation was observed and analyzed over a three-month period during which time the specimens were stored at 37 degrees +/- 1 degree C in an aqueous environment. The values of tensile strength covered a range from 24.9 MPa to 1.5 MPa depending on the particular material. Most of the materials displayed an increase in the module of elasticity over three-month period, but this increase was statistically significant in only one material (t-test, pmax < 0.00005). PMID- 8495950 TI - [A FEM study for the biomechanical comparison of labial and palatal force application on the upper incisors. Finite element method]. AB - The present study was designed to compare the biomechanical response of upper incisors to labial and lingual force applications. A three-dimensional finite element model was developed to analyze tooth displacement and stress distribution in the periodontal ligament. Lingually and apically directed forces of 1 N were applied at one point on the labial and at three points on the lingual surface of the crown. Tooth displacement and stress distribution resulting from lingual force applications were compared with those from the labial side. The following results were obtained: 1. Lingual horizontal forces produced similar patterns of tooth displacement and stress distribution, irrespective of the point of application (labial--lingual). 2. Apically directed vertical forces applied at the lingual points produced more uniform tooth displacements and stress distributions, although the force applied on the lingual side close to the CEJ, which happened to be most distant from the tooth's long axis, generated a pattern of movement somewhat different from the remaining two lingual force applications. The present results suggest the crucial role of the positional relation between the long axis of the tooth, respectively the center of resistance, and the point of force application. It can be deduced that lingual force application may produce more optimal tooth movement in terms of intrusion and subsequent stress distributions in the periodontal ligament. PMID- 8495951 TI - [The lateral and transverse forces with indirect headgear and its modifications]. AB - The use of the various variants of indirect headgear engenders transversal and lateral forces as an inevitable side effect. Direct clinical assessment of these forces, however, is not possible. To deal with this problem the study presented here employed 3D force sensors to measure in vitro the sagittal and transversal forces generated by diverse headgear modification. The results show that the transversal and lateral forces reach magnitudes which have direct clinical relevance. A common symmetrical indirect headgear, for instance, generates an expansive force that amounts to 20% of the distal. Transversal forces generated by expansion and compression headgear rapidly exceed therapeutically desirable magnitudes. All asymmetric headgear included in the study produced lateral forces which may lead to unwanted scissor or cross bites. The study presents a method whereby these inevitable lateral forces engendered by asymmetric headgear can potentially be minimized. PMID- 8495952 TI - [3-dimensional computed tomographic imaging of the dentate alveolar ridge. A radiological-histological comparison]. AB - Human bone segments of the toothed jaw with ten upper and ten lower teeth were scanned by high resolution computer tomography in continuous parallel axial and coronal slices (Somaton plus, Siemens). In both directions scanning was performed to 1 mm and 2 mm thicknesses and at 1 mm and 2 mm intervals. The jaw segments were dissected analogously in 1 mm thick slices. Contact films of the corresponding bone segments were exposed and then histological thin sections prepared. The statistical comparison between the CT exposures, the contact films, and the histological sections revealed an average absolute deviation of 0.3 to 0.5 mm with the axial CT exposures and a deviation of 0.3 to 1.6 mm with the coronal sections. It was possible to interpret in a quantitatively detailed manner the teeth and surrounding bone compacta up to a 0.5 mm minimum bone thickness. Computer-enhanced secondary reconstructions made possible an additional qualitative interpretation of the bone upper surface and the freely definable planes. Continuous parallel axial CT slices enable an interference free, proportionally accurate representation of the apical base, the periodontal bone structure, and the radice-root topography. PMID- 8495953 TI - The pathology of bone marrow transplantation. AB - The pathological complications of bone marrow transplantation are complex and may affect any organ in the body. The causes are often multifactorial and include the effects of chemotherapy, the conditioning regimen, drugs used in the post transplant period such as immunosuppressants and antibiotics, graft-versus-host disease (GvHD) and the effects of the primary disease itself. Infections are common and result from the immunosuppressive effects of cytotoxic drugs and irradiation, GvHD and marrow failure. Haemorrhage is not infrequent. Graft-versus host disease remains a significant problem and can be difficult to diagnose. Some of its histological features simulate the effects of chemoradiation and the diagnostic lesions may not be present early in the disease, when treatment is most effective. Evidence has accumulated that inflammatory cytokines have a key role in the pathogenesis of GvHD. It can be prevented by eliminating T-cells from the donor marrow but this procedure adversely affects marrow engraftment, increases the changes of rejection and results in a higher incidence of leukaemic relapse. Immunohistochemical staining for various cytokine-inducible molecules has led to some improvement in early diagnosis. PMID- 8495954 TI - Placental malaria. I. Pathological classification. AB - Pregnant women are more likely to contract malaria than their non-pregnant counterparts. The aim of this study was to develop a simple classification system for the histopathological diagnosis of placental malaria infection applicable to placentas collected in field conditions. The placentas were classified into four groups depending on the presence and distribution of parasites and malaria pigment: active infection, active-chronic infection, past-chronic infection, not infected. The frequency of parasitized placentas (26.4%) was in keeping with the prevalence of placental parasitaemia documented in epidemiological studies. An additional 29.8% placentas showed pigment in fibrin only, indicating past-chronic infection. Chronic placental malaria infection was most common in primigravidae, possibly reflecting ineffective clearance of parasites from the placenta. Seasonal fluctuations between infection categories support progression of placental infection with delayed clearance of pigment from fibrin. The proposed classification system has allowed diagnosis of different categories of placental malaria infection by two independent observers. A standardized method of diagnosis may enhance understanding of placental pathology and reduced birth weight in malaria infection during pregnancy. PMID- 8495955 TI - Placental malaria. II. A semi-quantitative investigation of the pathological features. AB - Malaria in pregnancy is associated with reduced birth weight. Most pathological studies of placental malaria infection have focused on severe Plasmodium falciparum infection. In the present study of 121 placentas delivered in a rural area of The Gambia, malaria infection was diagnosed in tissue sections using a simple classification system and severity of pathology was ranked semiquantitatively. Deposition of malaria pigment in circulating cells was associated with active infections whereas pigment in fibrin was a feature of active-chronic infections. Primigravidae had higher levels of pigment at all sites, although these observations were not always significant. Thickening of the trophoblast basement membrane occurred in all infection categories but fibrinoid necrosis of chorionic villi was a feature of active and active-chronic infection. Both birth weight and placental weight were increased in infected placentas but widespread trophoblast basement membrane thickening was associated with decreased birth weight. Both birth weight and placental weight decreased with increased fibrinoid necrosis and cytotrophoblast prominence but the results were not significant. By this approach it has been possible to correlate placental pathology with different infection categories and to analyse the pathological features associated with decreased birth weight. PMID- 8495956 TI - Idiopathic portal hypertension; a histopathological study of 26 Japanese cases. AB - Analysis of 25 liver biopsy specimens and one autopsy specimen from 26 Japanese patients (23 women and three men) with idiopathic portal hypertension revealed findings that collectively appeared diagnostic for the condition. Changes in the portal tract included capillary dilatation, phlebosclerosis, and fibro-elastosis of the stroma. Many portal veins were dilated and had herniated into the surrounding hepatic parenchyma. Portal vein obliteration and loss of bile ducts were a rare complication. The acinar architecture was disturbed by: 1) capillary and necro-inflammatory bridging, mostly between portal tracts and terminal hepatic veins; 2) the formation of isolated megasinusoids in a random distribution; 3) displaced and abnormally large hepatic vein branches with or without phlebosclerosis and 4) slender, curved fibrous septa (hairline septa). Early nodular regeneration was found in 25% of the cases. Our review supports the contention that incomplete septal cirrhosis may be a late manifestation of idiopathic portal hypertension. It is not clear whether the biopsy findings in Japanese patients differ only in severity from those in western patients, or whether the conditions differ pathogenetically. Some histopathological findings in the Japanese cases, in particular the necro-inflammatory changes, are difficult to reconcile with portal hypertension as a primary haemodynamic abnormality. PMID- 8495957 TI - Primary malignant melanoma of the rectum. AB - The diagnosis of a primary rectal malignant melanoma has been the subject of considerable argument for many years, principally on the grounds that extension from a primary anal lesion was often impossible to exclude. This paper provides evidence that certain melanomas can be recognized as primary rectal tumours, not only from careful anatomical assessment of the site of the tumour, but also by showing that they arise on a background of benign melanocytic proliferation in the rectal mucosa. The clinical presentation of these lesions, their possible mechanism of origin and their treatment is discussed. PMID- 8495958 TI - Aortic aneurysm in systemic lupus erythematosus. PMID- 8495959 TI - Mixed glioblastoma and malignant mesenchymoma, a variety of gliosarcoma. PMID- 8495960 TI - A case of Warthin's tumour with coexistent Hodgkin's disease. PMID- 8495961 TI - Double primary localized fibrous tumours of the pleura and retroperitoneum. PMID- 8495962 TI - Mixed medullary-follicular carcinoma of the thyroid occurring in familial form. PMID- 8495963 TI - Leiomyoma of the bronchus: a case report. PMID- 8495964 TI - Renal botryomycosis. PMID- 8495965 TI - Pseudoangiosarcomatous squamous cell carcinoma of skin. PMID- 8495966 TI - Spindle cell haemangioendothelioma: further evidence against its proposed neoplastic nature. PMID- 8495967 TI - Necrotizing sialometaplasia (adenometaplasia) of the trachea. PMID- 8495968 TI - Elimination of IgE regulatory rat CD8+ T cells in vivo differentially modulates interleukin-4 and interferon-gamma but not interleukin-2 production by splenic T cells. AB - Intraperitoneal immunization of Hooded Lister rats with a soluble antigen such as bee venom phospholipase A2 (PLA2), or ovalbumin (OVA) together with the toxic lectin, ricin, eliminates a population of early-activated CD8+ T cells which regulate IgE production. These early-activated CD8+ T cells are eliminated because they bear increased ricin-binding glycoproteins on their surface. This immunization regimen produces a vigorous and long-lived IgE response. The effect of this treatment on the capacity of splenic T cells to secrete interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and to generate IL-4 RNA message was assessed. IFN-gamma production by phytohaemagglutinin (PHA)- or ionomycin and phorbol myristate acetate (PMA)-stimulated splenocytes or purified splenic T cells from animals immunized with antigen and ricin was substantially reduced as compared with animals which were given saline or antigen alone (P < 0.001 Student's t test). At the height of the primary IgE response IFN-gamma production by PHA stimulated splenocytes was positively correlated with the number of CD8+ T cells (r = 0.90, P < 0.001) and inversely related to the level of serum IgE (r = -0.77, P < 0.020); serum IgE was inversely related to the number of CD8+ T cells (r = 0.92, P < 0.001). The reduced capacity of spleen cells from ricin and antigen immunized rats to produce IFN-gamma was first seen 7 days after immunization. The fall in the ability of splenocytes to secrete IFN-gamma closely paralleled the rise in serum IgE. IL-2 was assayed using an IL-2-dependent cell line which responded to rat IL-2 but not IL-4. Production of IL-2 by splenocytes taken from rats immunized with ricin+antigen was not significantly different to that produced by comparable cells obtained from animals immunized with antigen alone or saline. However, the levels of IL-4 mRNA, detected in ionomycin and PMA stimulated splenocytes using a quantitative polymerase chain reaction (PCR) procedure, were three- to fourfold higher in ricin and antigen immunized animals as compared with control animals. Following boosting with antigen and ricin the levels of IL-4 message detected increased a further three- to fourfold. These data show that the potentiated IgE response produced by immunization with antigen+ricin is associated with a decreased ability of splenocytes to produce IFN-gamma and an increased capacity to make IL-4. PMID- 8495969 TI - Induction and suppression of cytokine release (tumour necrosis factor-alpha; interleukin-6, interleukin-1 beta) by Escherichia coli pathogenicity factors (adhesions, alpha-haemolysin). AB - Escherichia coli bacteria expressing mannose-resistant fimbriae/haemagglutination induced the production of substantial amounts of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) from a peripheral human lymphocyte, monocyte, basophil (LMB) cell suspension. In this regard, E. coli bacteria with S mannose-resistant fimbriae/haemagglutination were the most potent inducers of IL 6 and TNF-alpha secretion, followed by the E. coli strain with P-mannose resistant fimbriae/haemagglutination. The E. coli alpha-haemolysin did not stimulate cytokine release from human LMB. In fact, this toxin, at non-toxic concentrations, depressed the spontaneous as well as the E. coli-induced production of TNF-alpha, IL-6, IL-1 beta. Our results indicate that two mechanisms may contribute to the severity of E. coli infection: (a) stimulation of cytokine release by type-specific fimbriae/haemagglutination properties and (b) depression of immune response by the E. coli alpha-haemolysin. PMID- 8495970 TI - T-cell lymphokine response to orally administered proteins during priming and unresponsiveness. AB - Feeding antigens induces an immunological unresponsiveness termed oral tolerance but under some conditions, for example following the administration of cyclophosphamide (CY), immunity can be induced. These observations have usually been made by studying antibody production and delayed hypersensitivity with little attention given to other measurements of cellular activation. We have therefore examined the lymphokines produced by T cells obtained after the induction of oral tolerance or intragastric priming. Cells isolated from the spleen and Peyer's patches (PP) of tolerized mice could secrete high levels of interferon-gamma (IFN-gamma) and moderate levels of granulocyte-macrophage colony stimulating factor (GM-CSF) in response to antigen while interleukin-2 (IL-2), IL 3 and IL-4 could not be detected. Mesenteric lymph node (MLN) cells of tolerized mice did not respond to antigen unless spleen adherent cells were added to the cultures where IFN-gamma and GM-CSF were produced. Intragastric priming was achieved by feeding antigen to CY-treated mice. T cells from the spleen, MLN and PP of these mice could produce GM-CSF, IFN-gamma, some IL-3 but little or no IL-2 and IL-4. The ability of MLN cells to proliferate with antigen in vitro was low and corresponded to low IL-2 production. Thus T cells from fed mice secrete a defined pattern of lymphokines which differs in tolerizing and priming regimes. PMID- 8495971 TI - Regulation by cytokines of eosinophilopoiesis and immunoglobulin E production in mice. AB - Certain clinical disorders are associated with eosinophilia and hyperimmunoglobulinaemia of the immunoglobulin (Ig) E class, but others give rise to eosinophilia without hyperimmunoglobulinaemia. To investigate why there are two such patterns, we immunized BALB/c mice with ovalbumin plus tetanus toxid with aluminium hydroxide gel (alum) as adjuvant, which caused eosinophilopoiesis and hyperimmunoglobulinaemia, and also immunized mice with the same antigens and complete Freund's adjuvant (CFA), which caused only eosinophilopoiesis. The difference in the adjuvant brought about the two different patterns. Monoclonal antibodies to four cytokines were used to find that eosinophilopoiesis was mediated by interleukin-5 (IL-5), whichever the adjuvant, and that IgE production in mice treated with alum was regulated by both IL-4 and IL-5. The lack of increase in IgE production was not due to suppression by interferon-gamma (IFN gamma) or by CD8+ T cells. By the polymerase chain reaction, both IL-4 and IL-5 mRNA were detected in cells from mice given alum, but only IL-5 mRNA was found in cells from mice given CFA. Thus, alum used as the adjuvant resulted in both eosinophilopoiesis and IgE production, but CFA resulted in eosinophilopoiesis alone. The dissociation between eosinophilopoiesis and IgE production shown in the mice given CFA could be due to the dissociation between the expression of mRNA of the cytokines IL-4 and IL-5 in vivo. PMID- 8495972 TI - Isolation and characterization of the soluble and membrane-bound porcine CD44 molecules. AB - Porcine CD44 was identified by the cross-reactive anti-human CD44 monoclonal antibody (mAb) Hermes-1. Material which inhibited the Hermes-1 mAb binding to porcine lymphocytes was found in porcine intestinal efferent lymph and demonstrated to be a soluble form of porcine CD44. A protocol using non-affinity techniques was established to isolate this material from porcine lymph. The isolated soluble CD44 molecule consists of a single peptide with an apparent MW of about 50,000, containing the Hermes-1 epitope. The soluble and membrane-bound forms of porcine CD44 were also affinity purified and characterized. The soluble CD44 preparation comprised a major component of 48,000-70,000 MW peptide and a minor band of 120,000 MW. The membrane-bound CD44 preparation contained a 90,000 MW major and a 120,000 MW minor component. Both the major components of the soluble and membrane-bound forms of porcine CD44 contained N-linked glycosylation. The 48,000-70,000 MW component of the soluble CD44 molecules consisted of two subsets discriminated by their binding capacity for lentil lectin and a slight difference in molecular weights. Soluble CD44 molecules were also identified in the sera of sheep, goats, horses, dogs and humans. Like the porcine counterpart, these molecules could be enriched by anion-exchange chromatography, suggesting that they have similar biochemical properties. PMID- 8495973 TI - Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood cells and involves reactive nitrogen intermediates. AB - Supernatants of human peripheral blood mononuclear cells (PBMC) incubated for 24 hr in the presence of extracts of freeze-thawed blood stage parasites of Plasmodium vivax or P. falciparum mediate inactivation of gametocytes of either species when incubated in vitro with whole human blood cells. Cultured P. falciparum gametocytes incubated with these malaria extract-stimulated PBMC supernatants in the presence of human blood from which white blood cells (WBC) had been removed were not inactivated. Thus the effects of the PBMC supernatants on gametocyte infectivity were dependent upon the presence of WBC. The suppressive effects mediated in the presence of WBC could be partially reversed in the presence of concentrations of 1 mM or higher of the L-arginine analogue NGL-monomethyl arginine acetate (L-NMMA). Our results indicate that the effects of WBC in inactivating gametocytes are due, at least in part, to a mechanism involving an L-arginine-dependent pathway. Previous studies have shown that the mediators of gametocyte inactivation in the stimulated PBMC supernatants comprised tumour necrosis factor (TNF) acting in conjunction with unidentified, but essential, 'complementary factors'. In the present study we show that these mediators, TNF and complementary factors, affect gametocytes indirectly through their interaction with WBC. PMID- 8495974 TI - Induction of macrophage parasiticidal activity by Staphylococcus aureus and exotoxins through the nitric oxide synthesis pathway. AB - Murine peritoneal macrophages stimulated in vitro with killed Gram-positive bacteria Staphylococcus aureus or its membrane components in the presence of interferon-gamma (IFN-gamma) expressed high levels of nitric oxide (NO) synthase and produced large amounts of NO in a dose-dependent manner. This is not due to the contamination by Gram-negative endotoxin because the stimulatory activity was not affected by the addition of polymyxin B. The expression of the NO synthase and the synthesis of NO by macrophages stimulated with toxic shock syndrome toxin 1 (TSST), lipoteichoic acid (LTA) or killed whole S. aureus together with IFN gamma was inhibited by the glucocorticoid, dexamethasone or by the specific inhibitor of NO synthesis, L-N-iminoethyl-ornithine (L-NIO). The exotoxins together with IFN-gamma also activated macrophages to kill the intracellular parasite Leishmania major. The leishmanicidal activity was completely inhibited by L-NIO. PMID- 8495975 TI - Identification of murine erythrocyte autoantigens and cross-reactive rat antigens. AB - Autoimmune haemolytic anaemia (AIHA) can be induced in mice by repeated injections with rat red blood cells (RBC). Here we describe the identification of murine RBC autoantigens and cross-reactive rat antigens. Sera and RBC eluates from the AIHA-positive mice immunoprecipitated a murine RBC autoantigen of 42,000 MW that comigrates with a zone of glycophorin in PAS-stained polyacrylamide gels. In addition, the eluates immunoprecipitated a 105,000 MW protein corresponding to band 3, the erythrocyte anion channel, and two further components of 34,000 and 29,000 MW within the glycophorin zone. The 42,000 MW band was not detected by immunoblotting, indicating that it bears autoantigenic epitope(s) that are denatured during electrophoresis. Cross-reactive autoantibody in the eluates immunoprecipitated a rat RBC protein that comigrated with band 3, together with two bands of 36,000 MW and 34,000 MW that may represent minor rat glycophorins. In contrast, rat-specific serum IgG from mice with AIHA reacted predominantly with major rat glycophorins of 75,000 MW and 38,000 MW. Immunoblotting revealed that normal murine sera contain IgG that binds autologous spectrin from the RBC membrane skeleton, and that this activity is increased in mice with AIHA. Sera from AIHA-positive mice also reacted with other internal murine RBC components that are not exposed on the surface of intact cells. It is evident from the data that immunization of mice with rat RBC results in the generation of multiple autoantibodies with a complex range of specificities. PMID- 8495976 TI - Production of a bifunctional hybrid molecule B72.3/metallothionein-1 by protein engineering. AB - A hybrid anti-tumour B72.3 antibody/metallothionein protein B72.3MT-1 was produced by the construction of the expression vector mpSV2neo-EP1-B72.3MT-1. This vector contained the neo gene as a selection marker, the murine immunoglobulin promoter and enhancer, and the hybrid B72.3 heavy chain gene fragment with mouse metallothionein-1 cDNA gene ligated into its CH2 domain. The expression vector was transfected to the heavy chain loss mutant B72.3Mut(K) cell line. The hybrid protein B72.3MT-1 was purified from transfectant supernates using a Protein G column. We showed that the hybrid protein retained the binding reactivity for the TAG72 antigen as the original B72.3 antibody, and the metal binding capacity of the native metallothionein molecule. Therefore, the bifunctional hybrid protein B72.3MT-1 may be very useful in cancer imaging when labelled with radionuclides such as 99mTc. PMID- 8495977 TI - Immunological analysis of the zinc-binding peptides of surface metalloproteinase (gp63) of Leishmania major. AB - The surface metalloproteinase, gp63, is highly conserved and immunogenic. A peptide spanning the zinc-binding region of the molecule is immunogenic and can induce protective immunity in mice against Leishmania major infection. We report here that the minimum length of the immunogenic peptide in this region is a heptapeptide, VVTHEMA, corresponding to residues 161-167. Optimal immunogenicity is conferred by a decapeptide, LVTVVTHEMA, corresponding to residues 158 to 167, where H and E are consensus zinc-binding residues. These two residues determine the specificity of the peptide. The next two residues, M and A are necessary for the immunogenicity of the peptide. These results suggest that the zinc-binding residues are recognized by the T-cell receptor complex, while the two adjacent residues are involved in the peptide presentation by the major histocompatibility complex (MHC) molecule. PMID- 8495978 TI - The I-Ab-restricted alloresponse of D10.G4.1 T cells is based on the recognition of an endogenous peptide. AB - The alloreactivity of T cells is thought to be based on the cross-reactive recognition of allogeneic major histocompatibility complex (MHC) molecules which have bound peptides derived from self antigens or, in the case of cultured T cells, from serum components. While studying the processing requirements of conalbumin (CA) that is recognized by D10.G4.1 T cells in combination with I-Ak molecules we also analysed the cross-reactive stimulation of clone D10.G4.1 T cells by allogeneic, I-Ab expressing stimulator cells which is shown here to be CD4 dependent. In order to distinguish between an endogenous or exogenous origin of a peptide that is presumably co-recognized with I-Ab different types of stimulatory/antigen-presenting cells (APC) were treated with drugs that are known to influence the processing and/or presentation of antigens. It was found that the alloreactive response of D10.G4.1 cells was abolished if the APC were treated with brefeldin A or inhibitors of protein biosynthesis. Under the same conditions neither the CA-specific response of D10.G4.1 cells nor the activation of control T cells by ovalbumin (OVA) or insulin was affected. On the other hand, the use of lysosomotropic agents or inhibitors of glycoprotein trimming had no influence on the ability of the APC to induce the alloresponse of D10.G4.1 cells, whilst the presentation of CA and other protein antigens by the APC was prevented. In addition, treatment of APC with pronase to remove surface MHC molecules or acidic buffer to remove peptides from the binding groove of MHC class II molecules at the surface of APC strongly diminished their ability to induce an alloresponse. However, this capacity was restored by incubating the APC for 2 hr in serum-free medium. These data indicate that the alloreactive response of D10.G4.1 cells is based on the recognition of newly synthesized endogenous peptide(s) in combination with I-Ab. PMID- 8495979 TI - Expression of the identical V beta gene in human T-cell clones does not confer the same pattern of responsiveness to bacterial enterotoxins. AB - Superantigens are the most potent T-cell mitogens so far described, and are believed to activate virtually all the T lymphocytes bearing the appropriate V beta segment in their T-cell receptor (TcR). In order to determine whether the expression of the identical V beta gene confers the same pattern of responsiveness to bacterial superantigens, we have established a panel of 20 untransformed human T-cell clones expressing the V beta 6.7a gene in their TcR. The V beta usage was defined by immunostaining, using the V beta 6.7a-specific monoclonal antibody (mAb) OT145, and confirmed by DNA sequencing of the beta chain. Although all the clones analysed expressed the same V beta gene, they had disparate patterns of proliferation to challenge with a panel of bacterial enterotoxins. This study demonstrates that the mere expression of the same V beta region by T lymphocytes does not grant an indistinguishable responsiveness to bacterial superantigens. Thus other, as yet undefined, T-lymphocyte components play a key role in the process of T-cell activation induced by bacterial superantigens, influencing the effects mediated by exogenous superantigens on human T cells. PMID- 8495981 TI - Cell-mediated immunity to HIV-1 in Walter Reed stages 1-6 individuals: correlation with virus burden. AB - Cell-mediated immunity (CMI) to human immunodeficiency virus-1 (HIV-1) was assessed in a blinded fashion for a patient group (n = 79) representing Walter Reed (WR) stages 1-6. At the same time, viral load was quantitatively measured by two different methods, specifically, virus isolation and HIV viral DNA copy number as measured by the polymerase chain reaction (PCR). After unblinding it was determined that the ability to generate a lymphoproliferative response to an inactivated gp120-depleted HIV (HIV-ag) and tetanus toxoid diminished with advancing WR staging, with complete anergy to HIV-ag and tetanus at stage 6. As a group, individuals whose peripheral blood mononuclear cells (PBMC) proliferated to HIV-ag were either virus isolation negative or produced low levels of virus as measured by p24 antigen (< 250 pg p24) on day 7. Similarly, HIV DNA copy number in the HIV-ag responders was low (< 200 copies/4 x 10(5) PBMC). In contrast, antigen proliferation to tetanus toxoid did not correlate with virus load. Thus, clinical progression as defined by the WR staging system appears to coincide with a loss of CMI to HIV. More importantly, the low viral load measured in HIV-ag responders suggests a link between viral burden and CMI to HIV which might be exploited in the design of immunotherapies for HIV-infected individuals. PMID- 8495980 TI - A comparative study of T-cell receptor V beta usage in non-obese diabetic (NOD) and I-E transgenic NOD mice. AB - The non-obese diabetic (NOD) mouse is a model for the study of insulin-dependent diabetes mellitus (IDDM). Recently transgenic NOD mice have been derived (NOD-E) that express the major histocompatibility complex (MHC) class II I-E molecule. NOD-E do not become diabetic and show negligible pancreatic insulitis. The possibility pertained that NOD-E mice are protected from disease by a process of T-cell deletion or anergy. This paper describes our attempts to discover whether this was so, by comparing NOD and NOD-E mouse T-cell receptor V beta usage. Splenocytes and lymph node cells were therefore tested for their ability to proliferate in response to monoclonal anti-V beta antibodies. We were unable to show any consistent differences between NOD and NOD-E responses to the panel of antibodies used. Previously proposed V beta were shown to be unlikely candidates for deletion or anergy. T cells present at low frequency (V beta 5+) in both NOD and NOD-E mice were shown to be as capable of expansion in response to antigenic stimulation as were more frequently expressed V beta. Our data therefore do not support deletion or anergy as mechanisms which could account for the observed disease protection in NOD-E mice. PMID- 8495982 TI - Cytotoxicity of unstimulated and thrombin-activated platelets to human tumour cells. AB - Platelet cytotoxicity was examined in vitro using various tumour cell lines as target cells. Thrombin-activated platelets as well as unstimulated platelets exerted a cytotoxic effect on some tumour cell lines including K562, KU812, LU99A and KG1, but other tumour cell lines including U937, MIA PaCa-2 and MOLT-4 were completely insensitive to this effect. Electron microscopic examinations showed that unstimulated platelets adhered to target K562 cells but thrombin-activated platelets did not. Morphological changes of K562 cells induced by unstimulated and thrombin-activated platelets were indistinguishable. When platelets and K562 cells were co-cultured in the same vessel but were prevented from coming into direct cell-to-cell contact by means of a membrane barrier, cytotoxicity of unstimulated platelets was completely blocked but that of thrombin-activated platelets was still detectable. However, no cytotoxic activity to K562 cells was detected in the supernatants obtained after stimulation of platelets with either target cells or thrombin for 4 hr. Extracellular Ca2+ ion was not required for the platelet-mediated cytotoxicity. Esterase inhibitors SBTI and TPCK had no effect on the formation of platelet-target cell adhesion but inhibited the cytotoxicity of unstimulated platelets. In contrast, the inhibitors had no effect on the cytotoxic activity of thrombin-activated platelets. These results suggest that direct contact between platelets and target cells is essential for unstimulated platelets but not for thrombin-activated platelets to exert cytotoxicity and that some esterases play a role in the cytotoxic process of unstimulated platelets. They also provide evidence that some cytotoxic effectors are soluble and easily inactivated factors liberated by activated platelets. Our findings indicate that platelets may be one of the cytotoxic effector cells against certain neoplasia. PMID- 8495983 TI - Emerging concepts in the management of acute lymphoblastic leukaemia. AB - Modern chemotherapy can cure more than 70 per cent of children with standard risk acute lymphoblastic leukaemia (ALL). Encouraging results are also reported in children with high risk ALL receiving intensive chemotherapy. Results in adults with ALL are less satisfactory, the long term survival is less than 35 per cent. Further dose intensification as possible in the setting of bone marrow transplantation (BMT) has increased the cure rate to 50 per cent in adult ALL. Allogeneic BMT has, however, besides the enhanced antileukaemia activity related to high dose therapy, additional antileukaemia effect related to immune mechanisms. Immune effects may be separated into three elements viz., an antileukaemia effect of graft vs host disease (GvHD), a separate antileukaemia effect of T cells and possibly a specific graft vs leukemia effect (GvL). These immune mediated antileukaemic effects offer a new potential therapeutic modality. For instance, the T cell antileukaemic effect of transplant could be achieved by transfusing radiated T cells or administering lymphokines. Alternatively autologous bone marrow could be manipulated in vitro prior to reinfusion. Manipulation might include activation of natural killer (NK) cells or lymphokine activated killer (LAK) activity. Another newer approach to treat ALL is the use of hemopoietic growth factors. Use of these factors prior to chemotherapy may increase the proportion of proliferating leukaemic stem cells. This would increase the efficacy of many drugs since most are active against proliferating cells. Hemopoietic regulatory factors could also be used to directly inhibit leukemic cell growth or to promote differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8495984 TI - Ultrastructural changes in esophageal mucosa of chronic tobacco chewers. AB - Seventeen chronic tobacco chewers and three control subjects underwent clinical evaluation, upper gastrointestinal endoscopy and esophageal mucosal biopsies. The esophageal biopsies were processed and examined under the electron microscope. A large number of ultrastructural abnormalities such as discontinuous, fragmented basement membrane, with reduction in hemidesmosomes, widened intercellular spaces were found in the esophageal mucosa of chronic tobacco chewers which resembled the ultrastructural features of experimental carcinogenesis and leukoplakia. It is concluded that chronic chewing of tobacco produces ultrastructural abnormalities in the esophageal mucosa which could be important precursors for esophageal malignancy. PMID- 8495985 TI - A field study on follow up at 10 years of prevalence of chronic obstructive pulmonary disease & peak expiratory flow rate. AB - In view of the paucity of follow-up field studies on patients of chronic obstructive pulmonary disease (COPD) with respect to smoking habits and lung function assessment, we undertook re-evaluation of COPD subjects 10 yr later. Of 2825 urban and 1556 rural subjects studied earlier between 1977-80, we re examined 846 (29.9%) and 629 (40.4%) subjects respectively in 1990. A questionnaire was filled and peak expiratory flow rate (PEFR) was measured in each subject. Symptomatic subjects were grouped into chronic bronchitis, simple (CB, S) and obstructive (CB, AO). The overall prevalence of COPD was 5.0 per cent in male and 2.8 per cent in female subjects. Prevalence of both CB, S and CB, AO were higher in the smokers. In the non-smokers, CB, AO prevalence was similar in the two sexes, but CB, S was commoner in rural than urban women. This simple, hypersecretory disorder was attributed to their exposure to biomass fuel combustion. The fall in PEFR, was significantly higher in smokers than nonsmokers, and more so in the symptomatic subjects with CB, AO. It was concluded that though the overall trend of prevalence of COPD in different groups did not change over the period, those with an initial airways obstruction had deteriorated significantly more than those with normal initial PEFR. PMID- 8495986 TI - Class specific antinuclear antibodies in systemic lupus erythematosus. AB - The incidence and significance of class specific antinuclear antibodies (ANA), specially with relevance to clinical manifestations of arthritis, renal disease and serositis was studied in 40 patients of systemic lupus erythematosus by the indirect immunofluorescent method. Clinical activity was scored by Morimoto's scoring system. A significant correlation was obtained between IgD ANA and clinical activity of the disease and IgG ANA exhibiting lupus pattern of immunofluorescence and serositis. PMID- 8495987 TI - Effect of aspirin on isoproterenol induced changes in lipid metabolism in rats. AB - The effect of aspirin on isoproterenol induced changes in lipid metabolism in rats was studied. Aspirin (1.2 mg/100 g/day) was administered orally for a period of 60 days along with/without isoproterenol (20 mg/100g sc twice at a time interval of 24 h for 2 days). Isoproterenol treated rats showed an increase in the levels of heart cholesterol, triglycerides and free fatty acids. The activity of cholesterol ester synthetase CES was increased significantly with concomitant increase in heart lipid peroxide levels in isoproterenol treatment. Aspirin treatment could restore the enzyme activity to near normal and also reduce the level of lipid peroxides. The lipid changes were minimum in rats treated with aspirin and isoproterenol. PMID- 8495988 TI - Enhancement of anti-inflammatory activity of aspirin by verapamil. AB - Verapamil in minimum therapeutic equivalent dose, failed to show anti inflammatory activity as did sub-anti-inflammatory dose of aspirin (54 mg/kg) however, when combined with sub-antiinflammatory dose of aspirin, significant (P < 0.001) inhibition of carrageenan and cotton pellet induced inflammation was observed. The anti-inflammatory activity of this combination treatment was almost comparable to that of the anti-inflammatory dose of aspirin (200 mg/kg), as confirmed by granuloma histology. Adrenal weight in the combination treatment group was similar to that of aspirin (200 mg) treated group and was significantly lower, as compared to controls. Further, a reduced ulcer index in the animals treated with combination (aspirin + verapamil), as compared to aspirin alone (200 mg) group, suggests its therapeutic potential. PMID- 8495989 TI - Frusemide-induced diabetes mellitus in insulin pretreated rabbits as an experimental model. AB - Single dose of frusemide 0.1 mg/kg orally was administered in 10 rabbits pretreated with soluble insulin 4 IU intravenously. Induction of diabetes after 24 h was confirmed by an increase in blood sugar and glucosylated haemoglobin and a decrease in serum insulin levels. Ten diabetic rabbits which received only frusemide without insulin pretreatment were used as controls, whereas equal number of insulin-pretreated rabbits receiving hydrochlorothiazide 250 mg/kg orally served as the positive control group. All biochemical parameters remained unaltered in the frusemide-treated test group as well as the positive control group after two weeks. The pancreatotoxic effect of frusemide may induce a stable hyperglycaemic state in rabbits which could lead to a useful diabetic model. PMID- 8495990 TI - Characterization of drowning by diatom test. AB - Examination by the diatom test, of different organs of corpses of individuals who died of drowning revealed the presence of frustules in all the visceral organs. Diatom load of different organs was found to be positively related with breadth/diameter of the frustule. Relatively larger diatoms were encountered in the lungs, heart and kidneys as compared to the other organs. Smaller diatoms up to 10 mu diameter were found in the brain, and bone marrow samples. However, diatoms were also recovered from the lungs, heart and kidneys of corpses of individuals in whom the cause of death was not drowning. Brain and bone marrow were considered reliable samples for executing the diatom test. PMID- 8495991 TI - Effect of nicotine administration on lipid metabolism in rats. AB - Administration of nicotine to rats resulted in increased concentration of cholesterol, phospholipids and triglycerides in the serum and tissues. HDL cholesterol decreased while the LDL + VLDL cholesterol increased. There was increased tissue cholesterogenesis as evident from the increased activity of HMG CoA reductase and increased incorporation into tissue unesterified cholesterol. Increased triglyceride synthesis in the tissues was evident from the increased activity of lipogenic enzymes and increased incorporation of label. Hepatic degradation of cholesterol to bile acids was decreased. The uptake of circulating triglyceride rich lipoproteins (chylomicrons and VLDL) was also decreased as revealed by the decreased activity of extrahepatic lipoprotein lipase. Plasma LCAT activity also showed a decrease in the rats given nicotine. The changes produced in the metabolism of lipids on nicotine administration were thus similar to those observed on exposure of rats to cigarette smoke, and it is felt that nicotine may therefore contribute at least partly to the risk posed by cigarette smoking in the development of atherosclerosis. PMID- 8495992 TI - Adaptive modeling in a mammalian skeletal model system. AB - Juvenile BALB/c mice were used as a model system to test the effects of various loading and exercise regimens on the growth and development of femora. Six treatments and three controls were used to document changes in geometric, mechanical, and material properties of the femora associated with strength. In each age-matched experiment, body weight and the strength, length, anterior and posterior diameters, cross-sectional area, moments of inertia in the anteroposterior and lateromedial directions, cortical wall thickness, and mineral content of the femora were assessed and found to vary significantly among treatment groups. An adaptive interpretation of these data was provided by calculating Pearson correlation coefficients between moment at failure (one measure of strength) and each geometric, mechanical and material property of the femora that contributes to strength. We make the assumption that at the termination of the experiment the greater the coordination between changes in strength and changes in the parameters that contribute to strength (the greater the number of correlations), the more adaptively modeled the femora are. Adaptive modeling here refers to the manner in which the femora grow and develop (adapt) under a given treatment regimen. Absolute strength of whole femora was reflected by our measure of adaptive modeling in all groups with one exception. In each experiment, the voluntary exercise controls were the most adaptively modeled. The least adaptively modeled groups also showed a general retardation of growth. It appears that juvenile mouse femora demonstrate a wide range of responses to different conditions of loading and exercise and that some of these changes are likely permanent. Moreover, at least two major variables--1) mechanical loading and 2) glucocorticoid mediated psychological stress--appear to contribute to the differences seen between the treatment groups. PMID- 8495993 TI - Increased atrial natriuretic factor prohormone peptides with aging in the heart, but not in lung, liver, or intestine. AB - Atrial natriuretic factor (ANF) has been found to be increased in the circulation of aged rats. The present investigation was designed to determine if the N terminal ANF prohormone peptides with blood pressure lowering properties are increased in the circulation of "aged" (24-26 months) versus "adult" (4-6 month old) Fisher 344 rats. We utilized two sensitive and specific radioimmunoassays that immunologically recognize the 98 amino acid (a.a.) N-terminus (proANF 1-98) and a.a. 31-67 (proANF 31-67, Vessel dilator) from the midportion of the N terminus of the 126 a.a. ANF prohormone. ProANF 1-98, and proANF 31-67, as well as ANF, were found to be elevated in the circulation of aged versus adult animals with proANF 31-67 and ANF elevations being significant at p < 0.05. To determine the potential source of the increased atrial natriuretic peptides in aged animals four tissue sources (liver, lung, heart, and intestine) from both adult and aged animals were examined. Hearts of aged animals contained significantly (P < 0.05; ANOVA) more proANF 1-98, proANF 31-67, and ANF than hearts of adult animals. There was no significant difference in the concentration of proANF 1-98, proANF 31-67, or ANF in the lung, liver, or intestine of the aged versus the adult animals. These results indicate that aged animals contained increased N-terminal and C-terminal ANF prohormone peptides in the circulation. The source of these increased peptides appears to be the heart. PMID- 8495994 TI - Growth regulation in Peromyscus species hybrids: a test for mitochondrial-nuclear genomic interaction. AB - Interspecific hybridization of Peromyscus maniculatus (deer mouse) and P. polionotus (oldfield mouse) is accompanied by pronounced size differences between reciprocal F1 animals beginning in the fetus and continuing throughout life. Since the mitochondrial genome is inherited through the maternal line in Peromyscus, we tested the hypothesis that increased disparity between the species sources of mitochondrial and nuclear genomes within animals would exaggerate the reciprocal size effects through misregulation of growth, whereas species compatible genomes were postulated to diminish the effect. Four series of backcrosses were established from females of the two reciprocal F1, while insuring continuity of the maternal mitochondrial composition at each generation. Size and weight measurements were made on neonatal, ten-day and six-month old animals through four or more backcross generations. Contrary to the hypothesis, deer mice with P. polionotus mitochondrial DNA, but 98% or more P. maniculatus nuclear composition, and animals with P. maniculatus mitochondria and principally P. polionotus nuclear genome regressed in mean size parameters to those of P. maniculatus and P. polionotus, respectively. Most of the regression was accounted for by the second backcross generation, and second and later backcross progeny did not differ significantly from the respective parental species controls. Maternal inheritance of mitochondrial DNA was confirmed by restriction enzyme analysis at the second and fifth backcross generation. Hybrid maternal effects in this Peromyscus cross are likely attributable to mechanisms other than nuclear mitochondrial genomic interaction. PMID- 8495995 TI - Alterations in thyroid metabolism are associated with improved posthatch growth of chickens administered bovine growth hormone in ovo. AB - Effects of in ovo administration of growth hormone (GH) on growth and thyroidal function of chickens were investigated in two experiments. In Experiment 1, fertile eggs were injected on day 11 of embryogenesis with vehicle (0.03 M NaHCO3, 0.15 M NaCl, pH 8.3) or vehicle containing 250 micrograms of pituitary bovine growth hormone (bGH) in trial 1 or containing 250 micrograms biosynthetic bGH in trial 2. In ovo administration of pituitary bGH but not biosynthetic bGH increased body weights and skeletal growth of male broilers at 3, 5, and 7 weeks posthatch. Seven-week-old males treated with pituitary bGH during embryogenesis exhibited decreased serum triiodothyronine (T3) levels and reduced liver-T4-5' monodeiodinase activity. Histological evaluation of thyroids from pituitary bGH treated broilers at 7 weeks posthatch indicated morphological alterations consistent with depressed thyroid function, including reduced amounts of non follicular tissue and increased mean follicular area. A second experiment was initiated to further investigate the effects of In ovo administration of pituitary bGH on thyroid metabolism. Fertile eggs were injected on day 11 of incubation with vehicle or 250 micrograms of pituitary bGH. At 5 weeks of age, serum T3 levels of broilers administered pituitary bGH in ovo were significantly increased as compared to controls following a challenge with 0.25 micrograms TRH/kg body weight. Circulating T3 levels were increased in response to 2.5 micrograms TRH/kg body weight in both control and in ovo GH-treated broilers. In both experiments, pituitary bGH administration resulted in significantly lower numbers of hatched chicks as compared to vehicle-injected chicks. Decreased hatchability, decreased circulating levels of T3, and increased sensitivity to TRH are evidence consistent with thyroid hypofunction. Reduced metabolic rate associated with decreased thyroid metabolism may have resulted in greater availability of energy for anabolic processes such as growth. PMID- 8495996 TI - Energy repletion and lipid metabolism during compensatory gain in broiler chickens. AB - Ross male broiler chickens were used to determine the effect of dietary energy on metabolism following a 6-day dietary energy restriction. Chickens were fed an amount of food (10 g) from 6 to 12 days of age calculated to only maintain body weight (maintenance energy) and not support appreciable growth. The chickens were then fed 1, 2, or 4x this amount of food for the period from from 13 to 21 days of age. Another group of chickens were also restricted from 6 to 12 days of age, but on an ad libitum basis from days 12 to 21. A control group was fed ad libitum throughout the experiment. All chickens were fed ad libitum from 21 to 54 days of age. Chickens were sacrificed at 12, 15, 17, 19, 22, 28, and 54 days. In vitro lipogenesis (IVL) and enzyme activities (isocitrate dehydrogenase; ICD, malic enzyme; ME, and glutamic oxaloacetic aminotransferase (GOT) were determined during the 12 to 28-day period and at 54 days. All restriction groups were lighter (P < 0.05) than controls at 28 days. Only chickens given 1x and 2x maintenance energy from 12 to 21 days were lighter (P < 0.05) than controls at 54 days. The 6-day energy restriction decreased (P < 0.05) IVL and ME and refeeding 2x and 4x maintenance restored IVL as did refeeding ad libitum. The greatest response was noted between 2 and 4 days following refeeding, surpassing controls at both periods. The significance of the present study lies in the findings that lipogenesis can be dosed against the energy intake following restriction and that changes in lipogenesis are very rapid, reaching steady state within 2 to 3 days. Furthermore, the growth data suggest that restriction regimens shift normal growth curves and compensatory growth may be an artifact of expressing data because smaller, younger birds have less fat than older birds. PMID- 8495997 TI - Age- and gender-related variations in the activities of drug-metabolizing and antioxidant enzymes in the white-footed mouse (Peromyscus leucopus). AB - The effects of aging on the activities of drug-metabolizing enzymes and antioxidant enzymes were studied in male and female White-Footed mice (Peromyscus leucopus) at ages of 6, 8, 12, 18, 24, 30, 36, and 48 months. Male mice had significantly higher liver microsomal cytochrome P450 (P450) content and NADPH:cytochrome P450 oxidoreductase (P450 reductase) activities than females at all age groups. Many of the P450-dependent enzyme activities were also generally higher in males. Female mice showed age-dependent decreases in P450 content and the activities of P450 reductase, pentoxyresorufin O-dealkylase (PROD) and N nitrosodimethylamine demethylase (NDMAd) in the liver from 6 to 24 months; while, the males showed an age-dependent decrease only for the liver PROD activity from 6 to 24 months. The old males (30-month old) appeared to have significantly higher activities for 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone and androstenedione formation than the middle-aged (6- to 18-month old) and very old (48-month old) males. Females showed age-dependent decreases for the formation of 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone in liver microsomes from 6 to 24 months. Lung microsomes from 6- and 8-month old males had much higher activities of ethoxyresorufin O-deethylase (EROD) and PROD than older males. The total NNK alpha-hydroxylation activities changed in the same pattern as lung microsomal EROD and PROD activities in both male and female mice. The activities of several phase II drug-metabolizing enzymes: glutathione S-transferase (GST), DT-diaphorase, sulfotransferase and UDP-glucuronosyl-transferase (UDPGT) did not show any significant age-dependent changes, with the possible exception that the GST activity in males decreased from 18 to 36 months. Males had about 3-fold higher UDPGT activities than females among all age groups. Glutathione peroxidase activities were drastically lower in old and very old males, and 6 to 24 months old males had significantly higher activities than the corresponding females. In females, superoxide dismutase activities decreased linearly to extremely low levels as mice aged. Catalase activities showed a tendency for increase with age in males. In conclusion, some P450-dependent activities and antioxidant enzymes, but not phase II drug-metabolizing enzymes, showed age-dependent changes; and most of these changes occur from 6 to 24 months. The demographic attributes of the White-Footed mouse are well-suited for physiological and biochemical studies of aging and can complement the more standard laboratory mouse model with its typical two year life span. PMID- 8495998 TI - Atopy and helminth parasites. PMID- 8495999 TI - The phylogenetic position of the Aspidobothrea within the parasitic flatworms inferred from ribosomal RNA sequence data. AB - Sequence data from parts of the small subunit ribosomal RNA gene (18s rRNA) from an aspidobothrean and two digeneans have been added to a published data set which includes sequences from a number of parasitic and non-parasitic flatworms. Parsimony and distance matrix analyses of the data were carried out. Tests for particular clades were done using bootstrap resampling methods, and tests of particular topologies done using 4- and 5-taxon tests. The aspidobothrean Lobatostoma manteri emerges from near the base of the Neodermata, but whether as a sister group to the rest of the Neodermata or as a sister to the Digenea alone cannot be determined from the number of nucleotide sites available. Gyrocotyle is included with the cestodes in a very strongly supported clade in all analyses. There is evidence that the Monogenea is a paraphyletic group, although more data are needed to confirm this possibility. PMID- 8496000 TI - Choice of mate, a reproductive isolating mechanism between Schistosoma intercalatum and S. mansoni in mixed infections. AB - In Africa, the two human schistosome parasites, Schistosoma intercalatum and S. mansoni, can be found sympatrically, which poses the problem of the nature of their reproductive isolation. In this paper, experimental studies of mating behaviour in mixed infections in mice were carried out. Simultaneous infections without choice of mate showed an absence of any physiological barriers preventing encounter and mating of the two species on the same host. Whenever choice was possible, mating did not occur in a random way, but preferentially between partners of the same species (there was a significant prevalence of homospecific pairs). S. mansoni exhibited greater specific mate recognition than S. intercalatum. Moreover, in the absence of S. mansoni female worms, S. mansoni male worms were as competitive as S. intercalatum male worms in pairing with S. intercalatum female worms. It appears from this study that the choice of mate is a reproductive isolating factor between the two species. PMID- 8496001 TI - Systematic relationships among pocket gopher chewing lice (Phthiraptera: Trichodectidae) inferred from electrophoretic data. AB - Multilocus starch-gel electrophoresis was used to obtain electrophoretic data for maximum parsimony, phenetic, and component analysis of systematic relationships among 14 species of pocket gopher chewing lice and two outgroup species. Pocket gopher lice studied included taxa representing seven of the 25 species complexes in Geomydoecus, and two of the four species complexes of Thomomydoecus. In pairwise comparisons, 12 of the 14 pocket gopher lice were characterized by two or more fixed genetic differences, and each nominal species possessed at least one fixed difference. These electrophoretic results are consistent with previous morphological analysis of species-level taxonomy. A maximum-parsimony analysis of the electrophoretic data yielded 80 trees, each with a length of 78 steps and a consistency index of 0.83. The strict consensus tree and the UPGMA phenogram of genetic distances indicate that five species of lice from Central American pocket gophers (Orthogeomys) form a clade distinct from lice hosted by North American pocket gophers (Geomys, Thomomys, and Cratogeomys). Other louse clades receiving reasonable support in bootstrap parsimony analysis include: (Thomomydoecus wardi, Th. minor); (Geomydoecus scleritus, G. mobilensis); (G. panamensis, G. setzeri); and (G. cherriei, G. costaricensis). The systematic results of this electrophoretic study are generally consistent with the boundaries of louse species complexes described previously. PMID- 8496002 TI - Relationship between eosinophilia and responsiveness to infection with Trichostrongylus colubriformis in sheep. AB - Lambs with genetically determined increased immunological responsiveness to Trichostrongylus colubriformis (high responders) had more eosinophils in cutaneous reactions to the mitogen phytohaemagglutinin (PHA) both before and during infection compared with those bred for susceptibility (low responders). In contrast, eosinophil numbers in both blood and cutaneous reactions elicited by third-stage T. colubriformis larval antigen were similar in high and low responders before infection. Following vaccination and challenge, high responders had elevated eosinophil numbers in blood and antigen-stimulated skin. In unselected sheep, although eosinophil numbers in cutaneous reactions to PHA were related to responsiveness to a challenge infection with T. colubriformis, there was a closer relationship between blood eosinophil numbers and responsiveness. Infection with T. colubriformis increased eosinophil numbers in cutaneous reactions to PHA and appeared to augment the difference between eosinophil counts in high and low responder sheep. Measurement of the ability to produce eosinophil activating factors, or for eosinophils to respond to such factors might therefore be useful in identifying individual sheep with increased responsiveness to T. colubriformis infection. PMID- 8496003 TI - The ultrastructure of the tegument and clamp attachment organ of Gotocotyla bivaginalis (Monogenea, Polyopisthocotylea). AB - The tegument of Gotocotyla bivaginalis consists of a syncytium, perikarya and four kinds of secretory bodies, viz. electron-dense granules, moderately electron dense vesicles, electron-lucent vesicles and large multivesicular bodies occurring in the ratio of 83:50:40:1. Microvillus-like structures, finger-like projections and a thin coat of glycocalyx occur on the In contrast, the syncytium of the clamp is relatively thin and irregularly folded, containing only three kinds of secretory bodies, viz. electron-dense granules, a few moderately electron-dense granules and several large electron-lucent vacuole-like structures in the ratio of 15:2:5. Exocytosis of the electron-dense and -lucent vesicles is apparently prevalent both in the syncytium of the haptor and general body surface. Tegumental damages induced by natural mechanical forces appear to occur in some regions of the syncytium of the clamps/haptor. Sclerites of the clamp are electron-dense and they are interconnected by the basal lamina, tendon and radial muscle fibres. Interstitial space is absent between the sarcolemma of adjacent muscle fibres of the clamp. Groups of neurons and non-myelinated nervous processes can be seen in the vicinity of the clamps. The axon is subdivided by invaginations of the neurolemma. Presumed non-ciliated mechano-receptors occur on the body surface. PMID- 8496004 TI - Lucilia cuprina: inhibition of larval growth induced by immunization of host sheep with extracts of larval peritrophic membrane. AB - A culture system has been established to produce gram amounts of peritrophic membrane from larvae of the sheep blowfly, Lucilia cuprina. Peritrophic membrane obtained from this culture has been used to immunize sheep. The immunization produced an immune response which resulted in the average weight of larvae on immunized sheep being only 50% of that of larvae grown on control sheep (P < 0.05). Fractionation of the components of the peritrophic membrane followed by immunization trials showed that the protective antigen fraction comprised material that could only be solubilized by harsh agents such as 4 M-urea. Even after solubilization by 4 M-urea, the protective antigens were able to produce a protective immune response which reduced growth of larvae on immunized sheep to 55% of larvae grown on control sheep (P < 0.05). This immune response which reduced growth of the larvae did not cause gross morphological damage to the larvae. PMID- 8496005 TI - Effect of chloroquine on hepatic heme-oxygenase during Plasmodium berghei infection in mice. AB - Hepatic heme-oxygenase and heme levels were monitored during Plasmodium berghei infection and chloroquine treatment in Swiss albino mice. A progressive increase in heme-oxygenase and heme levels was noticed with the rise in parasitemia. Further, chloroquine treatment did not result in any change towards normal heme oxygenase and heme content, when they were assayed a week after cessation of drug treatment. Chloroquine treatment of non-parasitized and parasitized mice resulted in significant loss of the enzyme activity after about 6 weeks. PMID- 8496006 TI - The development of Fasciola hepatica parthenitae in Lymnaea truncatula by modification of Muellerius capillaris infection. AB - Adult and juvenile Lymnaea truncatula (height 4 and 1 mm, respectively) were subjected to a dual infection with either Fasciola hepatica and Muellerius capillaris, or with M. capillaris and F. hepatica at 4-h, 7-, 14- and 30-day intervals between the two exposures. The results were compared with those of snails which had been infected with a single parasite species. In dually infected snails, there was a high mortality at the second exposure to both parasite species, and it was strongly increased by each reinfection. The interexposure time had a significant influence on these mortality rates. Histological examination demonstrated a decreased number of rediae (50% or greater) in dually infected snails beginning with the 4-h interval in adults and the 7-day interval in juveniles. The exposure order and the time interval between exposures had a significant influence on the number of rediae: the number of parasites per snail decreased as the time interval lengthened. Delayed maturity occurred in live free rediae in snails infected by F. hepatica and M. capillaris at the 14- and 30-day intervals. In those infected by M. capillaris and F. hepatica, time to reach maturity was not modified compared to that in snails infected with a single species. Prostronglylid larvae were clearly less numerous in dually infected adult snails than in corresponding mono-infected snails. Third-stage larvae were found in the 14- and 30-day groups, regardless of exposure order and were absent in mono-infected snails. PMID- 8496007 TI - The role of T cells in vaccine immunity in the murine model of schistosomiasis mansoni. AB - Naive CBA/Ca mice and mice vaccinated with gamma-irradiated cercariae of Schistosoma mansoni were challenged percutaneously with normal cercariae and depleted of L3T4+ T helper cells through the administration of a specific monoclonal antibody. Three regimes were utilized to target known phases of parasite migration. The in vivo depletion of L3T4+ cells resulted in a significant reduction in immunity (up to 65%) in vaccinated/challenged mice, provided the monoclonal antibody was targeted towards skin-resident schistosomula. When antibody was targeted towards lung phase challenge larvae, however, there was a significant reduction in worm recovery, but no correspondingly significant reduction in vaccine immunity. In contrast, the administration of monoclonal to naive mice, via all three treatment regimes, had no effect on the primary schistosome worm burden. Histopathological studies complemented these worm recovery data. Skin tissue biopsied from vaccinated/challenged mice treated with monoclonal to L3T4+ T cells rarely showed the inflammatory foci which normally characterize untreated vaccinated/challenged mice. This was true when antibody was given either before challenge, or just after challenge, and correlated with the recorded depression in vaccine immunity. Lung tissue collected from monoclonal-treated vaccinated/challenged mice (for all three treatment regimes) exhibited no changes in morphology compared to that from untreated vaccinated/challenged mice. This was not altogether surprising since in the NIMR vaccine mouse model, the lungs represent a poor site for challenge attrition and appear normal in morphology with the exception of a few, small inflammatory reactions. When the monoclonal was given to naive/infected mice, there was no change in the morphology of the pulmonary tissue, as compared to corresponding untreated cohorts. Immunohistochemical studies revealed that Thy-1+ cells dominated the subdermal inflammatory foci of vaccinated/challenged mice. Of the T cells identified, the T helper subset was the most common, with T suppressor cells being only weakly represented, and in some cases not at all. The proportion of macrophages (Mac-1+) varied between reactions. PMID- 8496008 TI - In vitro embryonation of Syphacia obvelata eggs. AB - Mouse infections with the pinworm, Syphacia obvelata, were evaluated as a potential model of human enterobiasis. Eggs of S. obvelata were found to be much less resistant to adverse environmental factors than those of Enterobius vermicularis, perishing rapidly when exposed to desiccation or to water. The average number of eggs produced by a female worm was 317 +/- 29 S.D. (range: 266 347), which is about 2-3% of the fecundity of E. vermicularis. Eggs expressed from gravid S. obvelata were incubated under various conditions, but the only reliable method of supporting complete embryonation was culture on a floating cellophane membrane. At 30 degrees C on this substrate, eggs were found to be infective between 6 and 42 h, inclusive. The pre-patent period in mice fed these eggs was 11-15 days. The more fastidious developmental and survival requirements of Syphacia eggs indicate that transmission of this species depends on much more intimate contact between hosts than is required by E. vermicularis. PMID- 8496009 TI - The potential value of integral membrane proteins in the vaccination of lambs against Haemonchus contortus. AB - An extract of adult Haemonchus contortus enriched in the parasite's intestinal microvillar membrane protein H11 and other integral membrane proteins but free of the protein contortin was evaluated as a potential vaccine in two breeds of sheep. The worm burdens of Clun Forest sheep injected with the extract and challenged with 25,000 infective larvae were reduced 89% by weight compared to the average for the controls. The worm burdens of Dorset sheep (challenged with 10,000 infective larvae) were reduced 72%. In both breeds the reduction in the number of female worms, 92 and 71.8%, respectively, was greater than the reduction in the males (86.5 and 46%). Parasite egg output, determined only for the Dorsets, was reduced 92% protection correlated with serum antibody titre. Most of the antibodies were directed against H11. PMID- 8496010 TI - Purification and evaluation of the integral membrane protein H11 as a protective antigen against Haemonchus contortus. AB - A detergent extract of adult Haemonchus contortus enriched in the integral membrane protein H11, previously shown to give protective immunity against the parasite, was fractionated by lectin and ion-exchange chromatography. The fractions were evaluated for their ability to immunize Clun Forest and Dorset Horn sheep against experimental haemonchosis. Most of the protective activity was associated with H11. Used in an approximately 95% pure form it gave a mean reduction in parasite egg output of 94.6% and reduced male and female worm numbers by 86.5 and 93.5%, respectively. Level of protection correlated with serum antibody titre to H11. PMID- 8496011 TI - Evidence for a G protein system in the tegumental brush border plasma membrane of Hymenolepis diminuta. AB - Guanine nucleotide-binding regulatory proteins (G proteins) mediate the transduction of signals from cell-surface receptors to intracellular effector enzymes. G protein alpha-subunits are routinely identified (and partially characterized) on the basis of their susceptibility to NAD(+)-dependent ADP ribosylation NAD(+)-dependent ADP-ribosylation catalysed by cholera and/or pertussis toxins. Analysis of purified tegumental brush border plasma membrane from Hymenolepis diminuta by relevant methodologies has revealed the presence of a 42 kDa putative G protein alpha-subunit that is susceptible to ADP-ribosylation by both cholera and pertussis toxins. This polypeptide shows no definite resemblance to any of the four major mammalian G protein classes on the basis of M(r) and toxin-susceptibility. These results provide evidence for the existence of a tegumental G protein-linked signal transduction system in H. diminuta. PMID- 8496012 TI - Structure and conformation of linear peptides. XIV. Structure of tert butyloxycarbonyl-L-alanylglycine monohydrate. AB - The crystal structure of a dipeptide tert-butyloxycarbonyl-L-alanylglycine monohydrate (C10H18N2O5.H2O), molecular weight 264, has been determined. The crystals are monoclinic, space group P2(1), with a = 10.767(1), b = 6.317(1), c = 10.981(2)A, beta = 109.15(2) degrees, and Z = 2, Dc = 1.24 g cm-3. The structure was solved by direct methods and refined to a final R-index of 0.045 for 856 reflections (sin theta/lambda < 0.55 A-1) with I > 2 sigma. The N-terminus of the molecule blocked with the t-Boc group is uncharged and the C-terminus exists in an unionized state. The peptide unit is trans and shows slight deviations from planarity. (delta omega = 3.1 degrees). The peptide backbone is folded, with torsion angles of phi 1 = -76.0(5), psi 1 = 164.3(4), omega 1 = 176.9(5), phi 2 = 116.1(5), psi 21 = -2.8(7) and psi 22 = 177.8(4) degrees. The conformation about the urethane bond (C5-N1) is trans. The urethane group is essential planar. The conformation of the boc group is trans-trans. PMID- 8496013 TI - Racemization of alpha-amino acid esters by aliphatic ketones in the presence of carboxylic acids. AB - Amino acid esters are racemized by dissolution in a mixture of aliphatic ketones and carboxylic acids. The racemization rate mainly depends on the structure of the amino acid and on the kind of ketone and carboxylic acid used, the best racemizing medium being acetone containing 15% acetic acid. The mechanism of the racemization and the practical consequences of this study in the optical resolution field are discussed. PMID- 8496014 TI - Synthesis and immunological properties of bombesin analogs. AB - Bombesin (Bn, pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2) is one of the most potent peptides, possessing a variety of physiological and pharmacological functions. We find from CD spectroscopy that the eight C-terminal residues of bombesin [Bn(7-14)NH2] have an ordered structure, and replacement of His-12 with Pro of Bn(7-14)NH2 changes the conformation from ordered to a more unordered form. Antibodies to Bn(7-14)NH2 cross-react to Bn and gastrin releasing peptide (GRP) in a dose-dependent manner. Antibodies to the Pro-analog do not recognize Bn or GRP. Substitution of the C-terminal amide by isopropylamide [Bn(7 14)NHC3H7(i)] makes its antibodies more specific to Bn than to GRP. It appears that this region of the peptide is an important antigenic determinant, which makes these antibodies differentiate between BN and GRP. PMID- 8496015 TI - Studies on the disproportionation of mixed anhydrides of N-alkoxycarbonylamino acids. AB - Mixed anhydrides from Z-valine and ethyl, isobutyl, isopropyl and isopropenyl chloroformate, and from N-tert-butoxycarbonyl- (Boc) and N-benzyloxycarbonyl- (Z) leucine and phenylalanine and Boc- and N-9-fluorenylmethoxycarbonyl-valine and ethyl chloroformate were purified and left in dichloromethane at 23 degrees C. The symmetrical anhydride (SyAn) generated after 24 h was determined by normal phase high-performance chromatography. No SyAn was produced from the anhydrides of Z- and Boc-valine; SyAn was produced from the other anhydrides. Anhydrides examined without isolation generally produced more SyAn than the pure compounds. More SyAn was generated in dimethylformamide and tetrahydrofuran than in dichloromethane, or in the presence of an excess of N-methylmorpholine or triethylamine. The anhydride from isobutyl chloroformate was much more stable than the anhydride from ethyl chloroformate. It is suggested that disproportionation of pure mixed carboxylic acid--carbonic acid anhydrides occurs by a bimolecular mechanism. PMID- 8496016 TI - Temporary serine protection in solid phase synthesis of LH-RH analogs. AB - Methodology for the large-scale, solid-phase synthesis of nafarelin, I, an LH-RH agonist and RS-26306, III, and LH-RH antagonist, is described. N alpha-Boc protected amino acids were used in the synthesis. The only side-chain-protected amino acids required were BocHis(Tos)-OH and BocSer(t-Bu)-OH. The use of temporary protection on serine eliminates the formation of bis-serine derivatives (II and IV), which presents a major limitation to the use of minimal protection schemes for large-scale synthesis. Using this approach, the side-chain protecting groups are cleaved during the synthesis, and HF deprotection in a separate step is not required. PMID- 8496017 TI - Solution conformations of the peptide backbone for DPDPE and its beta-MePhe4 substituted analogs. AB - The solution structures of DPDPE, a conformationally restricted pentapeptide with the sequence H-Tyr1-D-Pen2-Gly3-Phe4-D-Pen5-OH, and its four beta-MePhe4 substituted analogs were examined by a combined approach including the NMR measurements in DMSO and water as well as independent energy calculations. It was concluded that several low energy conformers of DPDPE backbone satisfy the NMR data obtained in this study as well as in previous studies by other authors. These possible solution conformers of DPDPE in both DMSO and water share virtually the same type of cyclic backbone structure, with the Gly3 residue in a conformation close to a gamma-turn, and the Phe4 residue in a conformation close to alpha-helical torsion angles. They differ in the space arrangements of the flexible Tyr1 moiety. The solution structures of the beta-MePhe4-substituted analogs of DPDPE are interesting. For analogs with an S-configuration at the C alpha atom in the Phe4 residue, the cyclic backbone conformations resemble those of DPDPE itself, whereas for analogs with an R-configuration at the C alpha atom, the backbone conformation is somewhat different. This observation is in line with the high biological potencies and selectivities displayed by the former compounds but not by the latter ones. It was noted also that as far as the peptide backbone conformers are concerned, some of the possible DPDPE conformers in water are similar to the previously suggested model for the delta-receptor-bound conformation of DPDPE, becoming virtually identical to this conformation by rotating the side chains of the Tyr1 and the Phe4 residues. PMID- 8496018 TI - Cyclic disulfide analogues of the complement component C3a. Synthesis and conformational investigations. AB - The flexible C-terminal region of the anaphylatoxic peptide C3a was reported to contain the receptor binding site. To elucidate the receptor binding conformation of the C-terminus, as well as to examine a synthetic approach to potential C3a antagonists, 26 cyclic disulfide bridged C3a analogues were synthesized. Solid phase peptide synthesis was performed on different polymeric supports by individual peptide synthesis, with Fmoc strategy, and simultaneous multiple peptide synthesis, using Boc and Fmoc strategies. Both strategies gave open-chain peptides in comparable yields. Syntheses using the Boc strategy employed the HF labile 4(methoxy)benzyl group (Mob) for beta-thiol protection of cysteine; in contrast, the TFA-stable protecting groups, acetamidomethyl (Acm) and trityl (Trt), were chosen for syntheses employing Fmoc strategy. Ring closure reactions by iodine oxidation were carried out starting from protected (Acm/Acm, Trt/Acm) or unprotected dithiols. The resulting cyclic C3a analogues were characterized by HPLC, amino acid analysis, and FAB-MS. Conformational investigations using CD spectroscopy and theoretical structural investigations by means of molecular dynamics calculations revealed that slight variations in sequence result in pronounced conformational consequences. The potential of cyclic C3a analogues to activate or to desensitize guinea pig platelets, a standard test system for biological activities of anaphylatoxic peptides like C3a, revealed relatively low activities for cyclic peptides (< 0.1% C3a activity). N-terminal acylation with cationic, arginine-rich sequences like YRRGR- led to amplified biological effects. Three of the synthesized peptides, namely CAALCLAR (P1), YRRGRCGGLCLAR (P5) and YRRGRAhxCGGLCLAR (P8), point in the direction of C3a antagonists. PMID- 8496019 TI - Chemical synthesis of a designed beta-protein through the flow-polyamide method. AB - A designed, 61-residue long, metal-binding protein was synthesized through the flow-polyamide method. This protein, named Minibody (Mini-antibody), contains a beta-sheet scaffold and two regions corresponding to immunoglobulin hypervariable loops (H1 and H2), onto which a metal binding site was engineered. The protein is extremely hydrophobic, with a 70% beta structure. Accordingly, it was anticipated, and actually found, to be a "difficult sequence" for all its length. Comparison of the standard, "minimum redundancy" protocol (single coupling, low excess of activated species) with a different protocol (double and triple coupling plus capping) showed that the two produced approximately the same amount of full-length product (3.7% after extensive purification). Capping was effective in blocking the unreacted amino groups, converting most failure sequences into truncated ones, a possible aid to implement affinity-type chromatographic protocols. Purification was complicated by the very low solubility of the molecule, coupled to a high tendency to aggregate even in concentrated chaotropic media (8 M urea). Nevertheless, a multi-dimensional purification scheme produced a highly homogeneous product, with the expected Ion Spray mass spectrum. The Minibody produced by recDNA methods showed identical chromatographic, spectroscopic and biochemical properties to those of the synthetic product. PMID- 8496020 TI - Molecular design of peptides. Synthesis, molecular structure and beta-turn II' formation of N-Boc-L-Phe-dehydro-Abu-NH-CH3 in crystals. AB - The peptide N-Boc-L-Phe-dehydro-Abu-NH-CH3 was synthesized by the usual workup procedure. The crystals grown from methanol at 4 degrees C belong to the space group P2(1)2(1)2(1) with a = 7.589(2), b = 13.690(4), c = 21.897(6) A, Z = 4 and dc = 1.149(5) g cm-3 for C19H29N3O5.CH3OH. The peptide crystals were highly sensitive to radiation. The final agreement factor R was 0.055 for 1109 observed reflections (I > or = 2 sigma) with data extending to a 2 theta value of 103 degrees. The methanol oxygen atom is split into two occupancies. Both sites are involved in identical hydrogen bonding. As a result of substitution of a dehydro Abu residue at the (i + 2) position the peptide adopts an ideal beta-turn II' conformation with torsion angles of corner residues as phi 1 = 63(1) degrees, psi 1 = -127(1) degrees, phi 2 = -66(1) degrees and psi 2 = -10(1) degrees, and an intramolecular hydrogen bond N-H...O of length 3.01(1) A. This shows that the conformational constraints produced by dehydro-Abu are similar in nature to but different in magnitude than those produced by dehydro-Phe and dehydro-Leu. The methanol-peptide interactions show characteristic features of multiple hydrogen bond formations involving polar sites of participating peptide and methanol molecules. The packing of the molecules in the unit cell is stabilized by interactions through methanol molecules with the help of several hydrogen bonds. PMID- 8496021 TI - Methionine-enkephalin related glycoconjugates. Synthesis and biological activity. AB - A series of glycoconjugates, in which [Met5]enkephalin or [D-Ala2,Met5]enkephalin have been linked through an ester bond to the HO-6 of various D-glycopyranose moieties, were synthesized by classical solution methods. The biological activities of these compounds were determined on selective pharmacological preparations: guinea pig ileum and mouse vas deferens for opioid activity, and two mouse cell lines, fibroblasts L929 and melanoma B16BL6, to study the influence on growth processes. The results reported in this study demonstrate the differential effect of the carbohydrate part in enkephalin-related glycoconjugates on receptor recognition. In addition, synthesized neo glycopeptides stimulate growth of the examined mouse cell lines, whereas parent peptide demonstrated some growth inhibitory properties. Full growth curves showed a dose-dependent effect at concentrations of 10(-7) to 10(-10) M. PMID- 8496022 TI - Application of anti-peptide antibodies to the assignment of the inter-chain disulphide bond in tetanus toxin. AB - Cysteine-containing peptides corresponding to the putative hinge region connecting the heavy and light polypeptide chains of tetanus toxin were synthesized utilising a solid phase with an acid hyper-labile linkage agent. Both the single-chain cysteine peptides, as well as a disulphide-bonded double-chain peptide, obtained by selective iodine-oxidation of S-trityl and S-acetamidomethyl protected peptides, were conjugated to carrier proteins for the purpose of immunisation and immunoassay. Comparison of the immunochemical specificity of mouse antibodies raised against these constructs, as well as antibodies against tetanus toxoid, permitted the assignment of the location of the inter-chain disulphide bond of tetanus toxin. PMID- 8496023 TI - Purging the emotions: the lack of emotional expression in subfertility and in the care of the dying. AB - The paper examines emotional expression by drawing on data from patients in two contrasting situations; interview data from couples attending fertility clinics, and audio-recorded conversations with terminally ill patients being cared for at home. Although the literature on subfertility and terminal illness frequently uses a bereavement model to argue for the importance of overt grieving, patients in these studies did not express a wish to discuss their feelings. This finding raises questions about how patients' needs are defined, and whether emotions may be created by discourse. PMID- 8496024 TI - Couvade syndrome in expectant Thai fathers. AB - The occurrence of somatic symptoms by expectant fathers, commonly referred to as the couvade syndrome, has been reported to exist in American and European males. The purpose of this study was to describe the incidence of the couvade syndrome in Thai males. Responses provided by 172 expectant Thai fathers indicate that they also experience somatic symptoms during their partner's pregnancy. PMID- 8496025 TI - Implications for nurses in approaches to the management of stroke rehabilitation: a review of the literature. AB - There is as yet no general agreement on how best to manage stroke rehabilitation in terms of the approaches to the management of this client group. Approaches include the Stroke Rehabilitation Unit (SRU), applying the principles of SRU management to general medical wards and the use of peripatetic stroke therapy teams. Each of these approaches has implications for nurses yet the contribution of nurses to the rehabilitation of stroke patients receives only scant attention in the literature. It is suggested that understating and undervaluing nursing leads to under use of this essential resource. PMID- 8496026 TI - The experience of terminal illness among Zulu speaking patients and their families. PMID- 8496027 TI - Finnish nurse instructors' view of the core of nursing. AB - The purpose of this article is to describe how nurse instructors understand nursing and the necessary conditions for high quality nursing care. The approach of the study was inductive and based on phenomenology and a sociological field research method, i.e. grounded theory. It emerged that the core of nursing is a process, termed here caring, with three stages. Three types of caring emerged. Understanding the client, the art of nursing, co-operation between the nurse and other health care professionals were found to be necessary conditions for a high quality nursing care and it was also found that it is not possible to separate caring from the society and its history. PMID- 8496028 TI - Phenomenology: one way to understand nursing practice. AB - This article reviews some of the debates about the relative merits of qualitative research and gives some examples of phenomenological enquiry in nursing. Given that nursing occurs in "the real world of practice", the view is forwarded that a research method chosen to understand nursing practice must be able to generate meaning from the people who are involved in nursing, that is, the nurses and patients in everyday practice settings. Phenomenology is suggested as a method for understanding nursing practice and some phenomenological research is reviewed. PMID- 8496029 TI - Subjectivity and culpability in the constitution of nurse-patient relationships. AB - The development and implementation of new modes of organizing nursing work, such as primary nursing, stress the quality of interpersonal relationships between nurses and their patients. It is important to recognize, however, that such relationships are inherently problematic. This paper explores, from a sociological perspective, nurses' orientations to interpersonal relations with patients and examines some of the sources of their problematic features. PMID- 8496030 TI - The General Electric-Association of University Radiologists Radiology Research Academic Fellowship (GERRAF). An industry-academic collaboration to improve clinical research in radiology. AB - The association of GE Medical Systems and the AUR represents a unique collaboration between academic radiology and industry that bears important potential for elevating the quality of clinical research in radiology and developing a cadre of high-quality radiologist researchers for the future. The establishment of the GERRAF is especially timely given the new imperatives of the rapidly changing health care environment, with its emphasis on expenditure reduction. The ultimate goals of GERRAF are to develop research leaders for radiology that will provide guidance for appropriate clinical practice, better train future researchers, and secure the role of radiologists in caring for patients. PMID- 8496031 TI - The effect of irreversible image compression on diagnostic accuracy in thoracic imaging. AB - RATIONALE AND OBJECTIVES: Digital image compression reduces the storage requirements and network traffic on picture archiving and communications systems. Full-frame bit-allocation (FFBA) is an irreversible image-compression method based on the discrete cosine transform that provides for high compression ratios with a high degree of image fidelity. METHODS: One hundred twenty-two posteroanterior chest radiographs were obtained on patients in an ambulatory patient setting, including 30 cases of interstitial lung disease, 45 images containing combinations of lung nodules (N = 37) or mediastinal masses (N = 39), and 47 normal images containing none of the pathology for which we were testing. The images were digitized (nominal 2 K x 2 K x 12-bit resolution), printed on a 35 x 35-cm hard copy format, and compressed at an approximate compression ratio of 20:1. Observer performance tests were conducted with five radiologists using receiver operating characteristics analysis on digitized uncompressed and compressed hard copy images. RESULTS: There were no significant differences between the two display conditions for the detectability of any of the thoracic abnormalities. CONCLUSIONS: Our preliminary results suggest that irreversible image compression at ratios of 20:1 may be acceptable for use in digital thoracic imaging. PMID- 8496032 TI - Comparison of oral cholecystography and ultrasonography for evaluating chronic cholecystitis using patient outcome as the reference standard. AB - RATIONALE AND OBJECTIVES: The authors compared oral cholecystography (OCG) with ultrasound (US) in the detection of chronic gallbladder disease using clinical outcome, rather than pathology results, as the reference standard. METHODS: The authors interviewed 269 patients who underwent either OCG, US, or both, for evaluation of chronic right upper quadrant abdominal pain. The authors considered patients who underwent cholecystectomy with improved symptoms 1 to 4 years after surgery to be reference-standard positive for gallbladder disease, and patients with objective evidence of an alternative diagnosis (eg, peptic ulcer disease), which improved with therapy as reference-standard negative. RESULTS: The sensitivity and specificity of OCG were 83% and 97%, respectively, and for US, 86% and 90%, respectively. CONCLUSIONS: OCG is comparable with US in evaluating of chronic gallbladder disease. In institutions where OCG is used for diagnosing chronic cholecystitis, it may be reasonable to continue using OCG. PMID- 8496033 TI - Single-exposure conventional and computed radiography. The hybrid cassette revisited. AB - RATIONALE AND OBJECTIVES: The authors constructed and evaluated a hybrid cassette for single-exposure extremity imaging with storage-phosphor plates and conventional radiographic film. METHODS: A hybrid cassette was constructed using a fine radiographic screen and a storage-phosphor plate. Exposures of a Lucite step wedge and a line pair gauge were made with the hybrid cassette, a conventional radiographic cassette, and a storage-phosphor cassette. The spatial resolution and imaging speeds of the hybrid and standard systems were compared. RESULTS: Spatial resolution loss was less than 0.5 line pairs per mm with the hybrid cassette. Speed loss was characteristic of the hybrid cassette, requiring approximately 40% greater exposure to produce the same film density as standard cassettes. CONCLUSIONS: The speed difference between this and a previous study is probably due to differences in film-screen choice, kilovolt peak, and storage phosphor plate generations. The sensitivity spectrum of our film and the emission spectrum of our screens were more closely matched than were the spectra in the previous study; we used lower kilovolt peak, and our storage-phosphor plates were a later, more efficient, generation. Despite slight speed losses, the hybrid cassette appears to be a better choice for obtaining matched images for clinical trials than the alternative of two separate exposures. PMID- 8496034 TI - Spatial resolution in digital mammography. AB - RATIONAL AND OBJECTIVES: Digital acquisition systems currently available limit spatial resolution in digital mammography to roughly 0.1 mm/pixel. The objective of this study is to determine if high-quality mammography is possible at this resolution. METHODS: The influence of spatial resolution on diagnostic quality was investigated by comparing observer performance on film to that on digitized film. A 0.1-mm sampling distance was used for digitization. Detection of mammographic details was studied by measuring threshold contrast as a function of detail size for small circular objects in the range of 0.12 to 2.5 mm. Characterization of microcalcifications was investigated in a receiver operating characteristic (ROC) study, in which 10 radiologists read 72 mammographic details with microcalcifications, both digitally and on film. RESULTS: Digitization improved the detectability of the larger, low contrast objects, whereas for small objects the detectability did not change. The authors found that even under the most optimal circumstances, isolated spherical calcifications with diameters smaller than 0.13 mm are not detectable with film-screen mammography, despite its resolution limit of 15 line patterns per mm (lp/mm). The ability to characterize microcalcification clusters did not change significantly with digitization. However, the results suggest that differentiation of benign from malignant cases decreases slightly, and that characterization of different types of malignancies somewhat improves by digitization. Mean differences between the two modalities were considerably smaller than the interobserver variability. CONCLUSION: A relatively low spatial resolution of 0.1 mm/pixel does not prohibit high-quality diagnostic performance in digital mammography. PMID- 8496035 TI - Gallbladder ablation with gallstones in situ in an animal model. AB - RATIONALE AND OBJECTIVES: The authors evaluated a method of gallbladder sclerosis in the presence of cholelithiasis. METHODS: The study was performed in 20 pigs. The gallbladders of 16 pigs contained surgically placed human gallstones. Control groups included animals that had their gallbladders sclerosed in the absence of stones, as well as a surgical sham control. Sclerosis followed cystic duct ligation to prevent extravasation of the sclerosing agent (95% Ethanol with 2 mole% trifluoroacetic acid) into the biliary tree. After sclerosis, a pigtail catheter was placed in the gallbladder to drain any post-procedure fluid accumulations. Catheters were removed after all drainage had ceased. Animals were killed at either 8 weeks (n = 6) or 6 months (n = 14). RESULTS: Stones were enveloped within the sclerosed and fibrotic gallbladder remnant in 13 of 15 test animals (87%). CONCLUSIONS: Sclerosis of gallbladders with stones in situ was achievable. Total mucosal obliteration did not appear to be required to produce a dysfunctional gallbladder in the time frame of this study. PMID- 8496036 TI - Scatter compensation for digital chest radiography using maximum likelihood expectation maximization. AB - RATIONALE AND OBJECTIVES: An iterative maximum likelihood expectation maximization algorithm (MLEM) has been developed for scatter compensation in chest radiography. METHODS: The MLEM technique produces a scatter-reduced image which maximizes the probability of observing the measured image. We examined the scatter content and the low-contrast signal-to-noise ratio (SNR) in digital radiographs of anatomical phantoms before and after compensation. RESULTS: MLEM converged to an accurate (6.4% RMS residual scatter error) estimate within 12 iterations. Both contrast and noise were increased in the processed images as iteration progressed. In the lung, contrast was increased 108% and SNR was improved by 10%. In the retrocardiac region, contrast was increased 180% while SNR decreased by 6%. CONCLUSIONS: This is the first report of a post-acquisition scatter compensation technique which can increase SNR. These results suggest that statistical estimation techniques can enhance image quality and quantitative accuracy for digital chest radiography. PMID- 8496037 TI - Evaluating bronchial drainage pathways in patients with lung disease using digital subtraction angiography. AB - RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate the venous drainage pathways of the bronchial circulation during bronchial embolotheraphy or infusion therapy. METHODS: The subjects consisted of 21 patients with lung disorders. All of them underwent bronchial arteriography for drug infusion or embolization. Bronchial arteriography was done using both cut-film and digital subtraction methods. RESULTS: The venous drainage pathways of arteriograms could be determined in 15 (71%) patients and classified into the four types: type 1, direct drainage into a pulmonary vein; type 2, drainage into a pulmonary artery with antegrade flow; type 3, drainage into a pulmonary artery with retrograde flow; and type 4, drainage into a bronchial vein. No drainage route could be identified in six (29%) patients. CONCLUSIONS: Digital subtraction angiography can depict the venous drainage pathways in most patients. Drainage occurs into a pulmonary vein in the majority of patients. PMID- 8496038 TI - Effect of contrast material osmolality on the electrocardiogram during intrauterine injection. AB - RATIONALE AND OBJECTIVES: In a previous study, intrauterine injection of meglumine-sodium diatrizoate (high osmolar contrast media) during hysterosalpingography was found to induce lengthening of the QTc interval on electrocardiography. To evaluate the relationship between high osmolality and electrocardiographic changes during intrauterine injection, the authors evaluated the effect on QTc of two ionic contrast agents with different osmolality during routine hysterosalpingography. METHODS: Forty-eight women undergoing routine hysterosalpingography were included in the study. Thirty-two women received meglumine-sodium diatrizoate (1500 mOsm/kg) and 16 received meglumine-sodium ioxaglate (600 mOsm/kg). QTc changes were evaluated using a 12 lead computerized electrocardiogram system during all the stages of the procedure. RESULTS: In the meglumine-sodium diatrizoate group, QTc interval was prolonged significantly from 419 +/- 19 msec at baseline to 447 +/- 30 msec during injection of contrast material, P < .001, and returned to baseline values in late phase (416 +/- 18 msec). The meglumine-sodium ioxaglate group showed no change in the QTc interval. CONCLUSION: As the single major difference between the two ionic agents is osmolality, we believe that QTc interval prolongation in the meglumine-sodium diatrizoate group is related to increased osmolality. PMID- 8496039 TI - Animal model of portal hypertension with observations regarding the relationship between portal flow and pressure. AB - RATIONALE AND OBJECTIVES: The feasibility of producing acute portal hypertension in a porcine model was evaluated to test the relationship between portosystemic shunt flow and portal pressure. METHODS: Percutaneous transhepatic cannulation of the portal vein and cutdown of a systemic vein was accomplished in anesthetized pigs. The portal system was subsequently embolized with polyvinyl alcohol (Ivalon) particles. Portosystemic shunting was performed with the assistance of a centrifugal pump. RESULTS: Portal hypertension could be routinely produced, and portosystemic shunting was successfully studied in three of four animals. Linear changes in shunt flow led to exponential pressure changes. CONCLUSIONS: This animal model provides a representation of acute portal hypertension that provides useful data regarding the compliance of the portal system and illustrates the pressure/flow relationship. PMID- 8496040 TI - Radiation hormesis. Its emerging significance in medical practice. AB - Because of the strong scientific evidence in support of radiation hormesis, we can no longer ignore this concept. There is, however, need for additional, carefully documented investigations in selected biological systems exposed to LLIR if the matter of radiation hormesis is to be settled once and for all. This need should be addressed without delay, as the matter of benefits derived from LLIR exposure could have major economic and epidemiologic implications. If radiation hormesis becomes firmly established, the requirements for LLIR protection might be relaxed, leading to a sizable cost saving, and the fear of nuclear energy should abate. If this happens, the evergrowing problems associated with energy production from fossil fuels on the one hand and the continued improvements in nuclear reactor technology on the other, will force a world-wide reassessment of risks and benefits associated with nuclear energy. Furthermore, as discussed herein, the major source of exposure from background radiation comes from the inhalation of radon gas. The very high cost associated with effective radon abatement would lead to an abandonment of this mitigation effort so that the limited funds available to improve public health world wide could be used more effectively elsewhere. Thus, we conclude that the time is now to consider eliminating the concept of the radiation paradigm from scientific thinking. We must not continue to unequivocally accept the propositions that 1) all radiation is harmful and 2) that the health effects of LLIR may be directly inferred by scaling down from known deleterious high-dose effects, in as much as there is no scientific basis for an agent not to cause multiple effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496041 TI - Hormesis and radiation protection. PMID- 8496042 TI - Digital image storage technology. PMID- 8496043 TI - Medical malpractice in France. The effects of a two-fold jurisdiction and the case of radiology. PMID- 8496044 TI - Life on the slippery slope. A bedside view of treating incompetent elderly patients. PMID- 8496045 TI - Caring and curing. A Medicare proposal. PMID- 8496046 TI - Am I my brother's warden? Responding to the unethical or incompetent colleague. PMID- 8496047 TI - Please pass the butter cookies. PMID- 8496048 TI - Hedging their bets. PMID- 8496049 TI - Are laws against assisted suicide unconstitutional? PMID- 8496050 TI - So sue. PMID- 8496051 TI - Brain metaphysics. PMID- 8496052 TI - To Moscow. PMID- 8496053 TI - "A quick and painless death". PMID- 8496054 TI - The family in medical decisionmaking. PMID- 8496055 TI - Headache associated with the Chiari type I malformation. AB - The main purpose of the present study was to define and understand more clearly the headache, and in particular the long-lasting attacks or continuous pain associated with the Chiari type I malformation. Of 34 patients with the malformation, the 20 patients who had or had had headache problems were interviewed according to a standardized questionnaire. Many patients had several headache types. Ten patients had shortlasting "cough headache" attacks lasting less than 5 minutes, 14 patients had relatively long-lasting attacks lasting from 3 hours to several days, and 8 patients had continuous headache. Unlike the short lasting cough headache attacks, long-lasting attacks were usually not precipitated by Valsalva-like maneuvers. With discriminant analysis, this headache could rather well be differentiated from that of migraine and cervicogenic headache patients. In many respects, however, this headache resembled cervicogenic headache with occipital and neck pain, pain in the arm, restriction of neck movement, and dizziness often accompanying the headache. Dizziness was the most distinguishing feature in the Chiari patients. These features, together with a beneficial effect of surgical treatment in some patients, suggest a causal relationship between the malformation and headache. From the histories of a few illustrative cases, it is suggested that the malformation may cause long-lasting headache attacks or continuous head pain by compression of the brainstem, central cord degeneration or intracranial hypertension. PMID- 8496056 TI - Headache in college students: a comparison of four populations. AB - Recent studies have reported a much lower rate of headache prevalence for Australian college students as compared with those for two campuses in the United States. We present such data here for a third U.S. campus and make several comparisons of these data for the four campuses. While the gender difference of higher female over male headache frequency was found for all four campuses, the same measure for combined genders is reliably higher for all three U.S. groups over their Australian counterpart and there are significant differences among the U.S. groups as well. Possible reasons for these campus differences in headache prevalence are outlined and discussed and further research is indicated. PMID- 8496057 TI - Disposition of naproxen after oral administration during and between migraine attacks. AB - Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Ten patients were treated with 500 mg of a soluble form of naproxen during and between migraine attacks. Clinical parameters and drug plasma levels were recorded at scheduled times. Pain reduction, from severe to mild was evident by 6.5 +/- 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients. PMID- 8496058 TI - Episodic paroxysmal hemicrania: 3 new cases and a review of the literature. AB - Episodic paroxysmal hemicrania (EPH) is a rare, benign disorder characterized by discrete bouts of hemicranial headaches separated by periods of pain-free remissions. EPH is frequently mistaken for episodic cluster headache because they have similar temporal profiles and clinical features. EPH is differentiated from cluster headaches by an increased frequency and a shorter duration of individual attacks. Establishing the diagnosis of EPH is important because of its unique response to treatment with indomethacin and not standard anti-cluster headache medications. PMID- 8496059 TI - Cerebral aneurysm presenting as cough headache. AB - The diagnosis of benign cough headache syndrome currently requires non-invasive brain imaging to exclude structural and mass lesions. We describe a patient with a cerebral aneurysm who presented with recurrent cough headache as her initial symptom. Conventional cerebral angiography was required for the diagnosis. Cerebral aneurysm should be considered in the differential diagnosis of cough headache syndrome. PMID- 8496060 TI - Non-compliance with follow-up and improvement after treatment at a headache center. AB - Two telephone surveys were conducted at a major headache center into patient compliance with follow-up and perceived treatment efficacy. The first survey addressed compliance with the recommendation to follow-up after the initial evaluation. Of a group of 316 consecutive patients, 40.5% had not complied with the recommended follow-up visit. Reasons for the non-compliance were given by 60.3%; most frequently mentioned were dislike of the clinician seen and seeking care elsewhere. The second survey concerned 75 patients who had returned at least once to the center for follow-up. When asked about the efficacy of the treatment received, 76.0% reported improvement of their headaches, with 32.0% reporting more than 75% improvement. In addition, 87.5% of the patients reported a decrease in the use of analgesic and/or ergotamine medications. We conclude that treatment of chronic headache is not a priori a hopeless situation and that in the patient compliance with the recommendation to follow-up, in particular the patient clinician relationship is a critical factor. PMID- 8496061 TI - The comparison of patients suffering from temporomandibular disorders and a general headache population. AB - The purpose of this study was to examine the possible association of signs and symptoms of temporomandibular disorders relative to headache. Fifty-six sequential patients referred to the Headache Institute of Minnesota for evaluation and treatment of migraine and tension headaches were examined for signs and symptoms of temporomandibular disorders. The results of the examination of headache patients were compared to patients suffering from myofascial pain dysfunction and/or TMJ internal derangements from the TMJ and Craniofacial Pain Clinic at the University of Minnesota. Finally the migraine and tension headache patients were compared to each other and an asymptomatic population. Results indicate that patients with temporomandibular disorders exhibit significantly more jaw dysfunction and pericranial muscle tenderness than migraine and tension headache patients. Migraine and tension headache patients were found to have similar amounts of pericranial muscle tenderness. Migraine and tension headache patients exhibited significantly more pericranial and neck muscle tenderness than a general population. PMID- 8496062 TI - Cluster headache in identical twins. AB - Twin brothers with cluster headache are described. Monozygosity was demonstrated by conventional genetic markers and DNA-typing. Both had "mini-bouts" in the early stages. In the one, attacks were always excruciatingly severe; in the other, they started out as "mild", eventually becoming more severe. Both brothers also suffered from paroxysmal tachycardia. The connection between attacks of tachycardia and cluster headache remains enigmatic. The observation of cluster headache in monozygotic twins underscores the importance of genetic factors in the etiology. The ratio between cluster headache prevalence in close family members vs. prevalence in the general population may be higher in cluster headache than in migraine. PMID- 8496064 TI - The caudalis portion of the spinal trigeminal nerve in the headache pathway--an hypothesis. PMID- 8496063 TI - Epidural, spinal and intramuscular morphine injections for lumbar puncture headache. PMID- 8496065 TI - Stadol Nasal Spray--treatment for migraine? PMID- 8496066 TI - Studies of the species barrier between Drosophila subobscura and D. madeirensis. III. How universal are the rules of speciation? AB - The prevalence of Haldane's rule and the large effect of the X chromosome are examined by analysing the genetics of seven abnormal characters in interspecies hybrids between D. subobscura and D. madeirensis. In two cases Haldane's rule is not obeyed (viability and abnormality of the head). In all characters except the abnormal abdominal tergites, an important effect of the X chromosome is observed. There is an asymmetry in the importance of the effect of the X chromosome. The X of D. madeirensis origin induces abnormality mostly in a mixed background. The Y chromosome plays an important role in determining male sterility. PMID- 8496067 TI - A further study of interchromosomal epistatic interaction in male mating activity of Drosophila melanogaster. AB - The interchromosomal epistatic interaction between second and third chromosomes was investigated for male mating activity of Drosophila melanogaster. The observed mating activity of double chromosome homozygotes is 0.526 +/- 0.044, whereas the expected one under the multiplicative model is calculated to be 0.511 +/- 0.038. These two male mating activities are in excellent agreement, indicating no interchromosomal epistasis. The coefficient of interaction, i, is quantified as -0.174 +/- 0.168. The magnitude of the k statistic, another index of epistasis, is 0.0001 +/- 0.0267. Neither index of epistasis differs statistically from zero. The result also shows that there is little or no epistatic interaction between two major chromosomes. However, one interchromosomal synthetic sterility was found in 26 chromosome lines. These results are combined with those of Kosuda (1985) and the generality of epistatic interaction is discussed. PMID- 8496068 TI - The effect of the inactive mutation on longevity, sex, rhythm and resistance to p cresol in Drosophila melanogaster. AB - Flies carrying the inactive (iav) mutation exhibit low locomotor activity and poor mating success, both of which are associated with a deficiency in the putative neurotransmitter, octopamine. Several other aspects of the iav mutant phenotype are described here. Male and female iav mutants show a small reduction in longevity but it is not clear whether this is a consequence of the iav mutation or their inactive phenotype. Young iav males show extended attractiveness to older courting males, which supports the notion that the iav gene has a role in post-eclosional maturation. The eclosion rhythm of iav mutants is normal, discounting the possibility of a role for octopamine in the maintenance of circadian rhythm. Flies carrying the iav mutation are highly susceptible to the octopamine analogue p-Cresol. Other phenotypically inactive flies show wild type levels of p-Cresol resistance. This is attributed to the deficiency of octopamine in iav mutants because low octopamine levels may be unable to out-compete the toxic effect of p-Cresol. Some inferences on the possible mode of action of the iav gene product are discussed. PMID- 8496069 TI - Laboratory and natural heritabilities of male courtship song characters in Drosophila montana and D. littoralis. AB - We estimated heritabilities for several male courtship song characters in two Drosophila species using father-son regression under conditions where both fathers and sons had been raised in the laboratory. In D. montana the heritabilities of song characters were rather high (-0.23 to 0.80) and in most cases significant. In D. littoralis the heritabilities of song characters were generally lower (-0.33 to 0.18), and none of them was significantly larger than zero. We also estimated heritabilities regressing characters of wild-caught fathers with those of their laboratory reared sons, and used the method employed by Riska et al. to estimate the lower bound of heritabilities in nature. In D. montana most and in D. littoralis all of the across-environment heritabilities were non-significant (-0.15 to 0.43 and -0.04 to 0.15, respectively), and in some cases the across-environment heritabilities were significantly lower than the heritabilities measured under laboratory conditions. The low across-environment heritabilities appeared to be due to larger phenotypic variability of song characters in the field and in some cases also due to genotype-environment interactions. PMID- 8496070 TI - Blindness from damage to optic chiasm. PMID- 8496071 TI - Treatment of hypoadrenocorticism in dogs. PMID- 8496072 TI - Equine rescue conference attracts international audience. PMID- 8496073 TI - Hyperkalemic periodic paralysis presents medical and ethical challenge. PMID- 8496075 TI - Trends in veterinarians' professional incomes, 1983 to 1991. PMID- 8496074 TI - Practice or perish? My path from practice to marketing to editing. PMID- 8496076 TI - Costs of clinical mastitis and mastitis prevention in dairy herds. AB - A stratified random sample of 50 Ohio dairy herds, monitored for 1 year between March 1988 and May 1989, was used to estimate the component costs of clinical mastitis per cow-year overall and by organism, the component costs of an episode of clinical mastitis overall and by organism, and the incidence of clinical mastitis by organism. Each herd was visited monthly by a veterinarian who conducted on-farm interviews and completed standardized data-collection forms designed to elicit economic information about the on-farm costs of clinical mastitis and mastitis prevention. Producers collected milk samples prior to treatment of clinical mastitis cases. Culturing methods allowed identification of 18 specific mastitis pathogen classifications. Annual costs estimated were on a per cow-year and clinical episode basis. The monthly mean population of cows monitored was 4,068. Mastitis prevention cost $14.50/cow-year, whereas the cost incurred by producers because of clinical cases of mastitis was $37.91. Organisms prevalent in the cows' environment caused the most costly types of mastitis. Disregarding contaminated samples and episodes for which no milk samples were taken, mastitis for which 2 organisms were isolated accounted for 35.5% of costs of clinical mastitis, followed by cases for which Escherichia coli (21.3%) was isolated, cases for which culturing yielded no growth (8.6%), and cases for which esculin-positive Streptococcus spp (6.4%), Klebsiella spp (5.7%), esculin negative CAMP-negative Streptococcus spp (5.1%), Enterobacter spp (4.8%), coagulase-negative Staphylococcus spp (4.1%), coagulase-positive Staphylococcus spp (3.0%), S agalactiae (2.5%), and Bacillus spp (1.2%) were isolated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496077 TI - Results of a survey of emergency evacuation of dairy cattle. PMID- 8496078 TI - Solving people problems. PMID- 8496079 TI - Postvaccination sarcomas in cats. PMID- 8496080 TI - Field trial of four cowside antibiotic-residue screening tests. AB - Four commercially available screening tests for antibiotic residues in milk were evaluated for their ability to correctly identify the antibiotic status of cows. A field trial, which included 199 cows from 2 herds, was conducted. Sensitivity, specificity, and likelihood ratios for a positive test result were calculated by using the Bacillus stearothermophilus var calidolactis disk assay as the reference test. The relationship of risk factors to the probability of a false positive result for each screening test was modeled by use of unconditional logistic regression. The risk factors evaluated in these models were loge somatic cell count (scc), intramammary infection, herd, milk appearance, time milk sample frozen before tested, days in lactation, parity, and manufacturer's lot number. The risk factors log(e) scc and intramammary infection were forced into all models. The overall specificities for the 4 tests ranged from 0.78 to 0.95, whereas likelihood ratios for a positive test result ranged from 4.54 to 20.0. When the confounding of cofactors was controlled in the logistic model, there was a positive effect of log(e) scc on the probability of a false-positive result for 3 of the screening tests, that is, for incremental increases in log(e) scc, there was an increasing likelihood for a false-positive result. In some of the tests, parity and intramammary infection also influenced the likelihood of a false positive result. The goal of cowside testing is to assist in the production of high-quality, antibiotic residue-free milk from dairies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496081 TI - Association between water sulfate and diarrhea in swine on Ohio farms. AB - Water samples and survey information related to prevalence of diarrhea, pathogens isolated, history of water quality problems, source of water, geographic location, land use, and water use were obtained from 54 swine farms in Ohio. Water was analyzed for concentration of sulfates and total dissolved solids by use of ion chromatography and electrical conductivity techniques. Sulfate concentrations in drinking water for swine ranged from 5.99 to 1,629 mg/L, with a mean of 231.78 mg/L and a median of 85.39 mg/L. Mean concentration of total dissolved solids was 632.2 mg/L, with a median of 581 mg/L and a range of 175 to 2,058 mg/L. Concentrations of water sulfate and total dissolved solids were highly correlated (P = 0.001). Sulfate concentrations were correlated with geographic location. Higher concentrations were found in the northern and western regions of Ohio. Associations between sulfate concentrations and prevalence of diarrhea, pathogens isolated, or source of water could not be established, but water sulfate concentrations significantly (P = 0.0002) increased with depth of the well. Water sulfate concentration could be approximated when geographic location, depth of well, and concentration of total dissolved solids were known. Sixty-nine percent (37/54) of the participating farms in the study had not had any laboratory-confirmed reports of diarrhea in swine in the preceding 2 years. Of those reporting diarrhea, most signs of disease were detected in pigs < 2 weeks old or in young pigs within 2 weeks of entry into the nursery. PMID- 8496082 TI - Photodynamic therapy for nasal and aural squamous cell carcinoma in cats. AB - Eighteen random-bred cats with a total of 19 nasal or aural squamous cell carcinomas were treated with photodynamic therapy, using aluminum phthalocyanine tetrasulfonate as the photosensitizer. Cats were irradiated at power densities of 100 mW/cm2 and energy densities of 100 J/cm2. Successful outcome was obtained in 10 tumors after 1 treatment, and 2 more tumors had complete responses after 1 or 2 additional treatments. Treatments were more effective in tumors of stage T2 or earlier. Five tumors had partial responses, and the response of 2 tumors could not be evaluated. The treatment was safe and well tolerated by most cats, although we found that cats should be kept out of sunlight for 2 weeks after treatment. PMID- 8496083 TI - Treatment of diabetic ketoacidosis in dogs by continuous low-dose intravenous infusion of insulin. AB - In a prospective clinical trial, low-dose, continuous, IV infusion of insulin (dosage, 2.2 U/kg of body weight, q 24 h) was used to treat 21 dogs with diabetic ketoacidosis. Mean (+/- SD) blood glucose concentration at the onset of treatment was 550 +/- 150 mg/dl and after 6 hours, was 350 +/- 106 mg/dl, with a mean decline of 34 +/- 16 mg/dl/h. By 12 hours, mean blood glucose was 246 +/- 85 mg/dl, with a mean decline of 28 +/- 14 mg/dl/h during the second 6 hours of treatment. Mean duration of treatment required to reach a blood glucose concentration < or = 250 mg/dl was 10 +/- 4 hours, with a range of 4 to 24 hours. Ketonuria was observed for 26 +/- 14 hours (range, 6 to 72 hours). Hypoglycemia developed in 3 of 21 dogs during treatment, but responded to IV administration of a glucose solution and to a reduction in rate of insulin delivery. Potassium supplementation was required in 15 of 21 dogs. Mean bicarbonate concentration was 11.6 +/- 3.4 mEq/L before treatment and was 18.2 +/- 0.7 mEq/L after 24 hours. Fifteen of 21 dogs (71%) survived to be discharged. Mean duration of treatment with the insulin infusion was 50 +/- 30 hours (range, 7 to 124 hours). In this series of dogs, continuous, low-dose, IV infusion of insulin provided a gradual and consistent reduction in blood glucose concentration while ketoacidosis, electrolyte balance, and dehydration were corrected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496084 TI - Paralytic syndrome attributed to lasalocid residues in a commercial ration fed to dogs. AB - Lasalocid, accidently introduced into a commercial dog food, was found to be the cause of neuromuscular toxicosis in 10 dogs. Toxicosis was confirmed in 4 principal dogs. The history, clinical signs, and pattern of onset of lasalocid induced toxicosis in the 14 dogs were similar to those reported for botulism. The signs, which were related to a generalized lower motor neuron deficit, were generally different from ionophore-induced toxicosis reported in other species. Supportive therapy and close monitoring were sufficient to bring about a gradual improvement in all of the dogs, despite the severity of clinical signs. PMID- 8496085 TI - Seizures and acute death attributable to hypovitaminosis A and suspected hypovitaminosis D in feeder pigs. AB - Clinical signs that included lethargy, inappetence, diarrhea, and vomiting and that progressed to seizures were observed in 40 feeder pigs that were approximately 70 days old. The pigs were fed ground red wheat and whole milk and were housed in a barn that did not allow exposure to direct sunlight. Analysis of samples of feed obtained from the farm indicated inadequate quantities of calcium and phosphorus as well as a low ratio of these 2 nutrients. Serum and tissue concentrations of vitamin A were less than normal. Low serum calcium concentrations, high serum phosphorus concentrations, and high alkaline phosphatase and creatine kinase activities were compatible with low vitamin D concentrations. PMID- 8496086 TI - Unilateral fibroepithelial hyperplasia of the mammary gland in a goat. AB - A 2.5-year-old female Nubian goat was admitted because of a mass involving the right mammary gland. Ultrasonography and cytologic examination of the mass revealed a benign or hyperplastic condition. A right mastectomy was performed. Results of histologic and immunohistochemical tests indicated mammary fibroepithelial hyperplasia (fibroadenomatous change), which is a condition usually found in cats. The mammary mass had not redeveloped in the goat after 1 year. PMID- 8496087 TI - Rhabdomyosarcoma of the tongue in a horse. AB - A 5-year-old Quarter Horse mare was examined because of a 6-month history of quidding and nasal discharge that contained feed material. Physical examination revealed weight loss and dorsal displacement of the soft palate, caused by a soft tissue mass located at the dorsal aspect of the base of the tongue. Surgical resection of the mass was successfully performed through an oral approach. The histopathologic diagnosis was rhabdomyosarcoma. PMID- 8496088 TI - Leptospiral abortion and leptospiruria in horses from the same farm. AB - Leptospirosis was documented as the cause of abortion in a 5-year-old mare. Leptospires were detected in tissue specimens from fetal kidneys and from placenta by histologic evaluation of silver-stained sections. Antibodies against Leptospira interrogans serovar pomona were detected in fetal serum at a titer of 1,600 by use of a microscopic agglutination test. The mare had serum titers of 6,400; 0; 400; 800; 3,200; and 6,400 to L interrogans serovars bratislava, canicola, grippotyphosa, hardjo, icterohaemorrhagiae, and pomona, respectively. A serologic survey identified titers of at least 6,400 against serovars bratislava and pomona in 5 other horses on the farm. Titers of at least 100 against serovar bratislava were detected in 53% of the horses on the farm. Leptospires were detected by direct fluorescent-antibody testing in urine samples from the mare that aborted and from 2 of the other 5 horses. PMID- 8496089 TI - Focal gingival hyperplasia in a horse. AB - A diagnosis of gingival hyperplasia in a 22-year-old Quarter Horse gelding was confirmed by histologic examination. Clinical signs included difficulty eating hay, and a large, intraoral soft tissue mass measuring 13 x 8 x 4.5 cm. The mass was located in the mucosa on the lingual aspect of the caudal left portion of the mandible, ventral to the base of the tongue, and covered the second and third lower molars, extending rostrally along the buccal mucosa to the premolars. The left maxillary second and third molars were overgrown with sharp edges. Lateral radiography of the mandible revealed absence of the left third molar, with associated bony irregularity and sclerosis. The horse was positioned in right lateral recumbency under general anesthesia, and the entire mass was resected. It was speculated that the lesion developed secondary to chronic irritation from opposing teeth and food-packing after loss of the lower third molar; this would not be an unexpected development in a species with continuously advancing molars. PMID- 8496090 TI - Hyphema associated with retinal disease in dogs: 17 cases (1986-1991). AB - We evaluated the medical records of 17 dogs with hyphema of presumed retinal origin to evaluate the clinical, laboratory, ultrasonographic, and histologic features as well as known complications. The mean age of the dogs was 11.5 years. Routine hematologic and biochemical evaluation failed to identify an underlying cause in any dog. Retinal detachments, however, were identified in 10 of 13 dogs evaluated by ultrasonography and 5 of 6 globes evaluated histologically. In 1 dog, hyphema was associated with retinal vascular disease, presumed to be caused by hypertension. The prognosis for vision in geriatric dogs with hyphema, secondary to retinal disease, was found to be grave, as 10 dogs developed secondary glaucoma. The outcome for all dogs was loss of vision. PMID- 8496091 TI - Basal sesamoidean fractures in horses: 57 cases (1980-1991). AB - Medical records of 57 horses admitted between 1980 and 1991 because of basal sesamoidean fractures were evaluated. Radiographic measurements of fragment size and fracture characteristics were recorded to determine their relationship to outcome. A successful outcome was assessed on the basis of the ability to return to racing, ability to race more than one time, and ability to finish first, second, or third. Any change in racing class also was assessed. There was a significant (P < 0.001) overrepresentation of Thoroughbreds, compared with other breeds in the hospital population. Fractures of the forelimbs accounted for 50 of the 57 fractures, and the right front medial sesamoid was affected significantly (P < 0.0001) more frequently than other proximal sesamoids. Fifty-nine percent of the horses returned to race at least 1 time regardless of treatment, and 41% finished first, second, or third. Horses with smaller fragments (shorter dorsopalmar length) tended to do better than horses with larger fragments. Horses without comminuted fractures tended to do better than horses with comminuted fractures, and horses with fragments only mildly (< 3 mm) displaced had significantly (P < 0.05) better outcomes than did horses with severe displacement of fragments. Only 19% of the horses with moderate (> 3 mm) displacement of fragments raced more than once, whereas 63% of horses with mild displacement of fragments returned to race more than once. Seventy-three percent of the horses that had the fragment removed surgically returned to race, and 57% dropped in class. Only 48% of the horses that did not have the fragment removed returned to race, and 87% dropped in class.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496093 TI - Question link between human lung cancer and pet bird exposure. PMID- 8496092 TI - What is your diagnosis? Dorsal cortical fracture of MC 3. PMID- 8496094 TI - Managing references. PMID- 8496095 TI - Comments on rabies and vaginal prolapse. PMID- 8496096 TI - BST approval gap narrows. PMID- 8496097 TI - Miracle at risk: is biomedical research endangered? PMID- 8496098 TI - Research training for veterinarians and graduate education in veterinary medical colleges. PMID- 8496099 TI - "Just for the love of it". PMID- 8496100 TI - More on case law involving cats. PMID- 8496101 TI - Association of abnormal uterine discharge with new intramammary infection in the early postpartum period in multiparous dairy cows. AB - The association of abnormal uterine discharge with the development of intramammary infection (IMI) was studied in 62 multiparous Holstein cows during the nonlactating period and from lactation days 3 through 30. Duplicate milk samples were obtained from each mammary gland at approximately day 30 of the nonlactating period. Milk samples for bacteriologic culture also were obtained from each gland from all cows at the end of the previous lactation, at parturition, and on a minimum of 7 additional dates during the first 30 days of lactation. Beginning after parturition and continuing once weekly for 4 weeks, each cow was examined, using a vaginal speculum to visually estimate the quantity of abnormal uterine discharge in the vagina. Additionally, uterine swab specimens were obtained for aerobic bacteriologic culture. Cows were allotted to groups on the basis of the maximal amount of abnormal uterine discharge observed at any 1 of the 4 examinations. Cows in group 1 had normal discharge or < 30 ml of abnormal discharge; in group 2, > or = to 30 ml of abnormal discharge, observed only on examination by vaginal speculum; and in group 3, > or = to 30 ml of abnormal discharge visible externally. A difference was not detected in the development of new IMI in the nonlactating period between cows that subsequently developed uterine discharge and those that did not. Although significant differences were not found, a tendency for lactating cows with abnormal uterine discharge to be at increased risk for developing new IMI was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496102 TI - Effect of sucralfate on healing of subclinical gastric ulcers in foals. AB - The effect of sucralfate on healing of subclinical gastric ulcers and gastric inflammation was investigated in twelve 6- to 7-month-old foals. Foals with endoscopically evident gastric lesions on day 0 were assigned to 1 of 2 groups, on the basis of mucosal inflammation and number and severity of ulcers, to create groups of foals with approximately equal severity of lesions. None of these foals had clinical signs of gastroduodenal ulcer disease. Groups were assigned to receive sucralfate (22.0 mg/kg of body weight) or corn syrup for 14 days, PO, every 8 hours. On day 15, gastroscopic examinations revealed that sucralfate did not promote greater healing than did the corn syrup. PMID- 8496103 TI - Megavoltage irradiation of neoplasms of the nasal and paranasal cavities in 77 dogs. AB - Seventy-seven dogs with malignant tumors of the nasal and paranasal cavities were treated by use of radiotherapy. The tumors included carcinomas (58) and sarcomas (19). Radiographic findings, including site of involvement and tumor extension, were the basis of clinical staging. Staging was performed according to the tumor, node, metastasis staging of the World Health Organization, and a modified staging scheme based on prognostic factors that seemed to correlate best with response to treatment. All irradiations were done with a telecobalt 60 unit. Fifty-six dogs were treated with irradiation alone, and 21 had partial tumor resection prior to radiotherapy. Treatment dose was 48 Gy (minimal tumor dose) administered on a Monday-Wednesday-Friday basis at 4 Gy/fraction over 4 weeks. The irradiation technique emphasized rostral field with a generous treatment volume. Duration of follow-up after irradiation ranged from 1 month to 61 months. The 1- and 2-year overall survival rates were 60.3% and 25%, respectively, and the 1- and 2-year relapse-free survival rates were 38.2% and 17.6%, respectively. Results of histologic examination and our modified staging scheme were significant (P = 0.02 and P = 0.04, respectively) prognostic factors of relapse-free survival. Conversely, tumor site, tumor extension, World Health Organization clinical stage, and cytoreductive surgery prior to irradiation did not affect the outcome of treatment. According to our modified staging scheme, dogs with stage-2- disease have a poorer prognosis than dogs with stage-1 disease, with a relative risk of relapse 2.3-fold higher. Dogs with carcinoma had a poorer prognosis than dogs with sarcoma (predominantly chondrosarcoma) with a relative risk of relapse 3.3-fold higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496104 TI - Insulin resistance in three dogs with hypothyroidism and diabetes mellitus. AB - Insulin resistance resolved in 3 dogs with hypothyroidism and diabetes mellitus after treatment with sodium levothyroxine. A thorough diagnostic evaluation failed to identify any other cause of insulin resistance in these dogs. Hypothyroidism was diagnosed in each dog on the basis of clinical signs, physical findings, hyperlipidemia, and results of thyrotropin or thyrotropin-releasing hormone stimulation test. Hypoglycemia was documented in each dog within 2 weeks of starting sodium levothyroxine administration. The insulin dosage was decreased by 60 to 62% during the ensuing months and good glycemic control was obtained at these lower insulin dosages in all dogs. These findings would suggest hypothyroidism-induced insulin resistance in these dogs. PMID- 8496105 TI - Omphalocele in two calves. AB - Two calves were found to have omphaloceles at the time of observed unassisted parturition. Both calves were admitted to the veterinary hospital within hours of birth. One calf, with the amnion covering of the herniated intestine and liver intact, was successfully treated by herniorrhaphy. The second calf had ruptured the amnion covering the hernia by the time of admission. This calf was euthanatized during laparotomy because of severe gross contamination of the abdominal cavity. An omphalocele is a congenital defect in the body wall in which eviscerated abdominal organs are covered by amnion rather than skin. PMID- 8496106 TI - Use of fenbendazole for treatment of Crenosoma vulpis infection in a dog. AB - An 8-month-old Labrador Retriever was examined because of a 1-month history of productive coughing unresponsive to ampicillin treatment. Larvae of Crenosoma vulpis were found in fecal samples examined by zinc sulfate centrifugation and Baermann technique. Physical examination abnormalities or larvae in fecal samples were not detected 6 weeks after treatment with prednisone (1 mg/kg, PO, q 24 h, for 7 days, then 0.5 mg/kg, PO, q 48 h, for 8 days) and fenbendazole granules (50 mg/kg, PO, q 24 h, for 3 days). This report suggests that fenbendazole may be effective for treating Crenosoma vulpis infection in dogs. PMID- 8496107 TI - Prescription and use of analgesics in dogs and cats in a veterinary teaching hospital: 258 cases (1983-1989) AB - The frequency of prescribing analgesics and administering them for the treatment of apparent postoperative pain in 243 dogs and 15 cats was evaluated. Surgeries performed on the animals evaluated included limb amputations, limb-sparing bone cancer resection, thoracotomy, cervical vertebral instability repair, and humeral fracture repair. Only 1 cat was treated once with an analgesic after surgery, and cats were not evaluated statistically. Dogs undergoing amputation, limb salvage procedure, or thoracotomy were more likely to be treated than dogs undergoing the other surgeries. Ninety-six (40%) of the 243 dogs were under the influence of an analgesic at any time during their postoperative hospital stay, and 69 dogs (28%) received 1 or more doses of an analgesic after recovery from general anesthesia. One hundred thirty-three dogs were cared for in the intensive care unit (ICU) immediately after surgery. Written instructions for treatment with an analgesic were given for 61 of those dogs, and 50 were given at least 1 dose of the prescribed analgesic. Dogs cared for in the ICU were twice as likely to be given an analgesic as dogs cared for in the surgery ward. The estimated duration of analgesic effect exceeded 8 hours in 46 (19%) of 243 dogs. Small and juvenile dogs were least likely to be treated. Interns and residents were twice as likely as faculty to administer analgesics. Most written interpretations of pain behavior observed in the ICU were made on the basis of vocalizations. Half of the dogs for which medical record comments suggested moderate to severe pain were not given an analgesic. The most frequently administered analgesic immediately following surgery was oxymorphone, followed by butorphanol and morphine. Aspirin was never administered to dogs in the ICU, but was used in 10 dogs that were in the surgery ward for > 74 hours. PMID- 8496108 TI - Packed red blood cell transfusions in dogs: 131 cases (1989). AB - One hundred and thirty-one dogs received 163 packed RBC transfusions in 1989, and records from these dogs were examined. Seventy percent had anemia from blood loss, 22% from hemolysis, and 8% from bone marrow hypoplasia. Forty-seven percent (62 dogs) survived hospitalization. Thirty-seven percent (49 dogs) required anesthesia for a surgical procedure. Thirteen percent (17 dogs) had acute or delayed transfusion reactions, but all of these dogs survived hospitalization. There was no age, breed, or sex predilection. Criteria used to determine transfusion need included anemia (measured by PCV); history of acute blood loss; need for anesthesia; and evidence of weakness, tachypnea, or tachycardia. Twenty four percent (32 dogs) scored < 5 on the transfusion-need assessment scale. These dogs may have had falsely low scores because of rapid blood loss from surgery or trauma without reflection in the PCV. PMID- 8496109 TI - What is your diagnosis? Radiopaque foreign body (10 x 15 mm) in the pelvic inlet and free peritoneal gas. PMID- 8496110 TI - Antidepressant treatments in children and adolescents: II. Anxiety, physical, and behavioral disorders. AB - Part II of this review critically evaluates antidepressants' (AD) efficacy in children and adolescents with anxiety, physical, and behavioral disorders as well as AD's side-effect spectrum. AD are administered increasingly to youths with specific anxiety syndromes phenomenologically paralleling those in adults which are responsive to AD (e.g., panic, obsessive-compulsive disorders). While several trials have not substantiated earlier theoretical considerations suggesting their usefulness in separation anxiety, their recent success in ameliorating obsessive compulsive symptoms is encouraging. Systematic drug treatment studies however are limited because of the common overlap of anxiety syndromes with each other and other prominent psychiatric disturbances. More consistent benefits with AD are seen in the physical (e.g., enuresis, bulimia nervosa) and behavioral disorders (e.g., attention deficit-hyperactivity disorder). The wide-ranging benefits of AD in nonaffective disorders suggest AD are more appropriately viewed as broad spectrum pharmacotherapeutics. PMID- 8496111 TI - Suicide in adolescents with no apparent psychopathology. AB - OBJECTIVE: To delineate the characteristics of adolescent suicide victims with no apparent psychiatric disorder. METHOD: Seven adolescent suicide victims with no apparent disorder were compared with 60 suicide victims with definite or probable psychiatric disorder, and with 38 community controls with no psychiatric disorder. RESULTS: Suicide victims without psychiatric disorder, compared with the remainder of suicides showed lower rates of past psychiatric treatment, previous suicide attempt, family history of affective illness, total life stressors over the previous 12 months, and a greater prevalence of the availability of a loaded gun in the home. The seven suicide victims compared with the 38 psychiatrically normal community controls, showed a higher rate of familial psychiatric disorder, past suicidal ideation or behavior, legal or disciplinary problems in the past year, and firearms in the home, particularly those that were loaded. CONCLUSION: Even suicide victims without apparent psychiatric disorder still show some evidence of psychiatric risk factors compared with community controls. However, prevention of suicide in this group is probably best achieved by restriction of the availability of firearms, particularly loaded ones. The clinician should pay particular attention to suicidal risk in youth who are confronting legal or serious disciplinary crises and should take suicidal ideation seriously even in the absence of clear psychopathology. PMID- 8496112 TI - Developmental psychopathology in suicidal and nonsuicidal adolescent girls. AB - OBJECTIVE: This study presents two distinct profiles of female suicide attempters based on social-cognitive development and investigates the relationship of both developmental and suicide risk variables in these profiles. METHOD: The sample included 139 girls, aged 13-16, admitted to an inpatient psychiatric hospital. Patients were divided into four groups based on their suicidal status (attempter/nonsuicidal) and ego development (preconformist/conformist level). RESULTS: Results support two developmental types of female suicide attempters that differed significantly on symptomatology, diagnoses, and defensive style. Preconformist attempters, the "angry-defiant" suicidal type, present with both depression and aggression as well as externalizing defense mechanisms. Conformist attempters, the "self-blaming" suicidal type, present with depression, and use more internalizing defenses to cope with conflict. Comparing suicide attempters and nonsuicidal girls, depression was found to be a risk factor for suicide at all developmental levels. Defense mechanisms were only associated with suicide at the preconformist developmental level. CONCLUSIONS: Social-cognitive development has an important impact on the expression of suicidal behavior in adolescent girls. PMID- 8496113 TI - Psychiatric sequelae to the loss of an adolescent peer to suicide. AB - OBJECTIVE: This study was designed to learn whether friends and acquaintances of suicide victims were at increased risk for depression, post-traumatic stress disorder, and suicidal behavior after exposure to suicide. METHOD: The social networks of 26 adolescent suicide victims, consisting of 146 adolescents, were interviewed 7 months after the death of the suicide victim and compared with 146 matched, unexposed controls. RESULTS: The rates of these disorders that had onset after exposure were elevated in the exposed group vs. controls: major depression, post-traumatic stress disorder, suicidal ideation with a plan or an attempt, but not suicidal attempts. Almost all of those exposed youth who developed new-onset suicidality did so in the context of a new-onset depressive episode. The majority of these new-onset depressive disorders began within 1 month of exposure. CONCLUSION: Postvention programs not only should focus on the prevention of imitation of suicidal behavior, but also should provide longer term follow-up for potentially bereaved and depressed youth exposed to suicide. PMID- 8496114 TI - Clinical components of suicidal intent in adolescent overdose. AB - Previous research has found that adolescents' statements about an overdose do not correlate well with their actions. This study examined the Beck Suicide Intent scale, which questions adolescents on their actions surrounding an overdose and on their beliefs as to its seriousness, in 50 adolescents after an overdose. The correlation between actions and belief was only 0.24. A factor analysis of the Beck Suicide Intent scale identified four factors labeled expressed intent, planning, concealment, and communication. It is suggested these factors could help clinicians making qualitative assessments of adolescent overdose. PMID- 8496115 TI - Psychiatric risk factors for adolescent suicide: a case-control study. AB - OBJECTIVE: The objective of this study was to determine the psychiatric risk factors for adolescent suicide. METHOD: Sixty-seven adolescent suicide victims were compared with 67 demographically matched community controls. Psychiatric disorder was assessed in suicide victims using a psychological autopsy protocol and in controls using similar semistructured psychiatric interviews. Risk factors were quantified by use of the odds ratio (OR), that is, the relative frequency of the occurrence of a given condition in the suicides compared with the controls. RESULTS: The most significant psychiatric risk factors associated with adolescent suicide were major depression (OR = 27.0), bipolar mixed state (OR = 9.0), substance abuse (OR = 8.5), and conduct disorder (OR = 6.0). Substance abuse was a more significant risk factor when comorbid with affective illness than when alone (OR = 17.0 versus 3.3). The majority of depressed suicide victims had a primary affective disorder (82%). A significant minority (31%) of depressed suicide victims had been depressed less than 3 months. Previous suicide attempts, suicidal ideation, and homicidal ideation also were associated with adolescent suicide. CONCLUSIONS: The development of effective treatments for youth who fit the above-noted risk profiles should be given high priority. PMID- 8496116 TI - Adolescent suicide: music preference as an indicator of vulnerability. AB - OBJECTIVE: This preliminary study investigated possible relationships between adolescents' music preference and aspects of their psychological health and lifestyle. METHOD: Students (mean age 14.76 years) from two randomly chosen high schools completed self-report questionnaires on preferred music types and messages in the music. In addition the Youth Self-Report provided information about suicide ideation, deliberate self-harm, "depression," and "delinquency." Brief risk taking and drug taking scales were administered in addition to questions about family environment. RESULTS: A marked gender bias was shown to exist with 74% of girls preferring pop music compared with 70.7% of boys preferring rock/metal. Significant associations appear to exist between a preference for rock/metal and suicidal thoughts, acts of deliberate self-harm, "depression," "delinquency," drug taking, and family dysfunction. This was all particularly true for girls. In addition, feeling sadder after listening to the preferred music appeared to distinguish the most disturbed group. CONCLUSIONS: The authors recommend that further academic study of these associations is warranted. Both preference for rock/metal music, particularly in girls, and feeling worse after listening to the music may be indicators in adolescents of vulnerability to suicidal thoughts and actions. PMID- 8496117 TI - Children of people with somatization disorder. AB - OBJECTIVE: The author investigated psychopathology, suicidal behavior, child abuse, somatization, and health care utilization in 34 children with a parent who has somatization disorder (SD-P) and two comparison groups: 41 children with a somatizing parent (SOM) (fewer symptoms than required for diagnosis of SD-P), and 30 pediatrically ill controls (CON). METHOD: Child and parent versions of the Diagnostic Interview for Children and Adolescents were scored for diagnosis and symptom counts in specified categories. Medical records were obtained and abstracted. RESULTS: Children of SD-P had significantly more psychiatric disorders and suicide attempts than did children of SOM or the CON. SD-P and CON had significantly more unexplained physical symptoms than SOM. SD-P showed a trend toward more hospitalizations and experienced significantly more maltreatment. CONCLUSIONS: Children of SD-P are at significant risk in several respects. Clinical implications of these findings include a need for awareness and cooperation among general psychiatrists, primary care physicians, and child and adolescent psychiatrists to facilitate detection and treatment of these children's problems. PMID- 8496118 TI - Psychosocial and family functioning in children with sickle cell syndrome and their mothers. AB - OBJECTIVE: The purpose of this study was to compare the psychiatric functioning of 61 sickle cell youth and their families with nondiseased sibling controls. METHOD: Functioning assessed by multiple informants included indices of behavioral, cognitive, and family/interpersonal functioning, self-esteem, life events, coping strategies, temperament, adaptive behavior, and parental psychopathology. RESULTS: Key findings were that sickle cell patients evidenced more depressive symptoms and associated attributional style, and externalizing behavioral difficulties than did nondiseased siblings. With age, sickle cell youth evidence increasing adaptive behavior deficits and internalizing symptoms. Illness severity was related to symptoms of internalizing behavior and fewer daily living skills. Associations were found between maternal and child coping. CONCLUSIONS: It is recommended that psychiatric consultations routinely be conducted with these children, particularly at times of family stress and developmental transitions. Psychiatric interventions should focus on ameliorating emotional difficulties via enhancing adaptive coping strategies. PMID- 8496119 TI - Parental psychopathology and children's adjustment to leukemia. AB - OBJECTIVE: The primary purpose of this study was to examine the relationship between parental psychopathology and psychosocial functioning of children in whom acute lymphocytic leukemia (ALL) has been diagnosed. METHOD: The sample consisted of 61 mother-child dyads. Twenty-one (34%) mothers met DSM-III-R criteria for at least one psychiatric disorder based on a Structured Clinical Interview for Diagnosis (SCID). RESULTS: Findings revealed that compared with children whose mothers did not meet DSM-III-R criteria for a psychiatric disorder, children with mothers who evidenced a psychiatric disorder self-reported more anxiety and a maladaptive attributional style and were reported by their mothers as evidencing more depression and a range of internalizing behavioral symptoms. CONCLUSIONS: Although our earlier research suggested that ALL children show relatively few symptoms of psychopathology, the present report reveals high rates of psychiatric difficulties in the mothers of ALL youth. These findings and their implications are discussed within a model that incorporates behavioral pediatrics and developmental psychopathology. PMID- 8496120 TI - Anxiety and intrafamilial stress in children with hemophilia after the HIV crisis. AB - OBJECTIVE: The 12-month prevalence of DSM-III-R anxiety disorders and intrafamilial stress ratings were determined in 23 children with hemophilia, 37 children with asthma, and 31 healthy children. METHOD: Diagnoses were made using the parent and child versions of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), and intrafamilial stress ratings were obtained using the Index of Family Relations (IFR). RESULTS: HIV-positive boys with hemophilia had significantly higher rates of anxiety disorders than did the other comparison groups (p = 0.05), mainly owing to a high rate of separation anxiety disorder. Intrafamilial stress ratings were highest in the asthma group, where 29.7% of the children and 24.3% of the parents reached clinically significant scores. CONCLUSIONS: Anxiety disorders appear to be common in HIV-positive children with hemophilia; however, they report little intrafamilial stress. PMID- 8496121 TI - Adult criminality among formerly hospitalized child psychiatric patients. AB - Among 170 preadolescent children (138 males, 32 females) admitted to the University of Iowa Psychiatric Hospital between 1970 and 1983, 23 males (17%), had adult prison records at follow-up in 1990. Assaultive behavior in childhood predicted adult imprisonment (odds ratio = 4.96, 95% confidence interval 1.8 13.8, p = 0.002), as did criminality in a biological parent (odds ratio = 4.0, 95% confidence interval 1.3-12.4, p = 0.015). Diagnosis, including conduct disorder, was not correlated with outcome. Among these young children, male gender, violence, and parental criminality identified persons at high risk for adult imprisonment. Psychiatric hospitalization in childhood is a risk for adult disturbance, including sociopathy. PMID- 8496122 TI - Treatment of aggressive children with clonidine: results of an open pilot study. AB - Seventeen aggressive children (14 boys and 3 girls) aged 5 to 15 years, who were characterized by cruel behavior to others and destruction of property, entered an open pilot study using clonidine to evaluate its efficacy and safety and drug induced changes in plasma gamma aminobutyric acid (GABA). Aggression decreased in 15 children with minimal side effects. In five cases, GABA increased from 105.4 +/- 15.2 ng/mL at baseline to 125.2 +/- 10.8 ng/mL at follow-up (p < 0.01). A sixth patient was noncompliant. These findings suggest that GABA may be correlated with childhood aggressiveness and may be a useful marker of drug compliance. Pharmacotherapy with clonidine should be further assessed for the control of aggression. PMID- 8496123 TI - Language, learning, and behavioral disturbances in childhood: a longitudinal perspective. AB - OBJECTIVE: Investigate longitudinally the course of development of preschool learning impaired (LI) children to better understand the interaction between neurodevelopmental delay, behavioral/emotional disorders, and language development and disorders. METHOD: Relationships between developmental language disorders and emotional problems were investigated in 99 8-year-old specifically language impaired and control children originally assessed at age 4 years using the Achenbach Child Behavior Checklist and the Conners' Parents Questionnaire. RESULTS: LI children received higher behavior problem scores and were more likely to score in the clinical range than were control children. Neither degree of early language impairment nor amount of language improvement predicted 8-year behavioral/emotional status. LI children with the largest drop in IQ between ages 4 and 8 received the highest behavior problem scores. No significant comorbid relationship was seen between LI and attention-deficit hyperactivity disorder. CONCLUSIONS: The enhanced incidence of behavior problems reported heretofore may be related more to lower IQ than to linguistic deficit per se. Care must be taken to differentiate the symptoms of neurodevelopmental delay and emotional disturbance, however, preschool children with scores in the clinical range on such measures should be referred for additional evaluation. PMID- 8496124 TI - Unsuspected language impairment in psychiatrically disturbed children: prevalence and language and behavioral characteristics. AB - OBJECTIVE: This study examined the prevalence of unsuspected language impairments in 4-12-year-old psychiatric outpatients. METHOD: Children (N = 399) were routinely screened with standardized language tests, and parents and teachers completed behavioral checklists. RESULTS: Results indicated that of 288 children referred solely for a psychiatric disorder, 99 (34.4%) had a language impairment that had not been suspected previously. These children had more subtle language impairments than did the 111 children referred with previously identified language impairments. Both children with unsuspected and previously identified language impairments had symptoms associated with attention-deficit hyperactivity disorder. Children with unsuspected language impairments had the most serious externalizing behavioral problems. CONCLUSIONS: Attention needs to be paid to screening children for language impairments and to helping adults understand how language disabilities impact on communication and behavior. PMID- 8496125 TI - Communication deficits in children undergoing temporal lobectomy. AB - OBJECTIVE: To examine formal thought disorder and discourse (cohesive) devices that make speech coherent prospectively in seven children, aged 5.7 to 16.7 years, before and after temporal lobectomy for intractable cut points determined from sensitivity and specificity analyses of formal thought disorder and discourse measures in 22 children with complex partial seizure disorder and 45 normal children. RESULTS: Before surgery, the mean illogical thinking and discourse scores of the surgical candidates were in the pathological range. After a mean postoperative follow-up period of 15.1 months, their illogical thinking (but not their discourse scores) decreased significantly to the normal range. CONCLUSIONS: These preliminary findings are discussed in terms of the possible role of postsurgical changes in seizure control, behavior, antiepileptic drugs, cognition, and prefrontal function. PMID- 8496126 TI - Magnetic resonance imaging in patients with concurrent Tourette's disorder and Asperger's syndrome. AB - OBJECTIVE: The purpose of the study was to examine behavioral/cognitive and neuroradiological features of patients with concurrent Tourette's disorder (TD) and Asperger's syndrome (AS). METHODS: The authors studied the occurrence of structural brain abnormalities using magnetic resonance imaging (MRI) in seven males with concurrent TD and AS, and in nine age-matched males, who had TD but did not have AS. Both groups were tested with an extensive battery of neurological and psychiatric rating scales and cognitive tests. RESULTS: Five of the seven patients with TD and AS had developmental brain anomalies. In contrast, normal MRI scans were found in all but one TD patient without AS. Both groups were not significantly different in the severity of motor and phonic tics, obsessionality, depression and anxiety, or in measures of general intelligence, memory, and language function; but patients with TD and AS had a history of more psychiatric hospitalizations, poor academic achievement, more neurological soft signs and appeared more impaired on complex problem-solving and spatial tests than did TD patients without AS. CONCLUSION: These findings suggest that structural cortical and subcortical abnormalities are more common among individuals with concurrent TD and AS than among sex- and age-matched TD patients without AS. Dysfunction of frontal-subcortical systems may play a role in the pathophysiology of concurrent TD and AS. PMID- 8496127 TI - Acute dystonic reaction with low-dose pimozide. AB - It is essential to recognize individual susceptibility to neuroleptic-induced side effects for treatment guidelines. This paper reports on a 6.9-year-old autistic male who developed repeated episodes of acute dystonic reactions associated with pimozide administration at the doses of 0.096 mg/kg/day and 0.032 mg/kg/day and 32 hours following pimozide withdrawal, as well as during subsequent thioridazine administration. It draws the clinician's attention to unusual susceptibility to extrapyramidal side effects and suggests that if a child shows this type of susceptibility to one neuroleptic, he/she may react similarly to other neuroleptics as well. PMID- 8496128 TI - The Diagnostic Interview Schedule for Children-Revised Version (DISC-R): I. Preparation, field testing, interrater reliability, and acceptability. AB - OBJECTIVE: To describe the history and assessment strategies used to investigate and revise the Diagnostic Interview Schedule for Children (DISC), a highly structured interview form used by lay interviewers to elicit diagnostic criteria for the common psychiatric disorders of childhood and adolescence. METHOD: Revision was based on clinical and community data that identified unreliable and undiscriminating items in an earlier version of the instrument (DISC-1). A field study was carried out with 74 parent-child pairs. Interrater reliability and acceptability to patients was high. Accompanying papers describe the test-retest and construct validity of the instrument. CONCLUSIONS: Taken together, the findings suggest that the DISC is an acceptable, brief, inexpensive, and convenient instrument for ascertaining a comprehensive range of child and adolescent diagnoses whose methodological properties are comparable with other child diagnostic instruments. PMID- 8496129 TI - The Diagnostic Interview Schedule for Children-Revised Version (DISC-R): II. Test retest reliability. AB - OBJECTIVE: Test-retest reliability and internal consistency of the Diagnostic Interview Schedule for Children-Revised Version (DISC-R) were examined to evaluate the effects of a recent revision process. METHOD: A sample of outpatients 11 to 17 years old and their parents were administered the DISC-R in a test-retest design. RESULTS: For the parent interview, four diagnoses had sufficient cases to examine reliability; agreement was good to excellent for three of these. For the child interview, two of the four diagnoses with adequate cases showed good or excellent reliability. Using a combined parent-child algorithm, three of five diagnoses showed good or excellent reliability. Test retest reliability for symptom scales was excellent for the parent DISC-R and good for the child version, except for oppositional defiant disorder. Maternal depressive symptoms did not affect reliability of reporting about the child's symptomatology. Internal consistency was satisfactory for symptom items comprising most diagnoses. CONCLUSIONS: Although some revision of the instrument will be necessary, the findings from this study suggest that the DISC-R is a promising research instrument for the diagnosis of psychopathology in older children and adolescents. PMID- 8496130 TI - The Diagnostic Interview Schedule for Children-Revised Version (DISC-R): III. Concurrent criterion validity. AB - OBJECTIVE: To examine the concurrent criterion validity of the Revised Diagnostic Interview Schedule for Children (DISC-R), a structured lay-administered instrument designed for use in community studies, under conditions designed to provide strict controls for information and method variance. METHOD: The DISC-R was compared with a semistructured clinical interview that covered a similar information base as the DISC-R, used standardized ratings to record symptom information, and, similar to the DISC-R, was scored by DSM-III-R-based computerized diagnostic algorithms. Subjects were 74 child and adolescent clinic attendees and their adult custodians. RESULTS: Overall, moderate levels of agreement were found between DISC-R and clinician-generated diagnoses; these findings were tempered, however, by the fact that the validation interview was less reliable than the DISC-R. CONCLUSIONS: Although these findings provide preliminary support for the use of the DISC-R, they cast some doubt on the adequacy of clinician-generated diagnoses as validation criteria and suggest that alternate approaches to the assessment of validation should be pursued. PMID- 8496131 TI - Sensitivity of the Diagnostic Interview Schedule for Children, 2nd edition (DISC 2.1) for specific diagnoses of children and adolescents. AB - OBJECTIVE: The sensitivity of the Diagnostic Interview Schedule for Children, second edition (DISC-2.1) was examined for certain "rare" disorders: eating disorders, major depressive episode, obsessive compulsive disorder, psychosis, tic disorders, and substance use disorders. METHOD: Subjects recruited from specialized centers were interviewed with the DISC-2.1; the centers' diagnoses served as the criterion measure. RESULTS: Overall the DISC showed good to excellent sensitivity (range = 0.73 to 1.0). Used alone, the DISC-P (parent interview) was generally more sensitive than the DISC-C (child interview). Areas for additional instrument revision were identified. Recommendations about informant choice by diagnosis are offered. CONCLUSIONS: The strategy used in this study was useful for assessing the DISC's sensitivity for these disorders. Additional work examining specificity of the DISC remains to be done. The DISC should prove a useful adjunct in clinical settings given the ease and relatively low cost of administration. PMID- 8496132 TI - Structured diagnostic interviews and clinicians' discharge diagnoses in hospitalized adolescents. AB - OBJECTIVE: In this study Diagnostic Interview Schedule for Children (DISC-C) and clinicians' discharge diagnoses, as well as clinicians' admission and discharge diagnoses were compared. METHOD: Patients (N = 163) ages 12 to 16 were interviewed with the DISC-C during the first month of admission. The frequencies for different diagnoses by DISC-C and by clinicians at the time of admission and discharge were tabulated. Kappa coefficients were obtained from cross-tabulated frequencies of DISC and clinicians' discharge diagnoses. RESULTS: At discharge, the clinicians diagnosed more patients with multiple diagnoses and also diagnosed more patients with conduct and substance abuse disorders, dysthymia, and psychosis than they did at admission. The DISC-C diagnosed more patients with these disorders, except with psychosis, than did clinicians at either admission or discharge. The agreement between the clinicians' discharge and DISC-C diagnoses remained low across the diagnostic categories. CONCLUSIONS: These findings support the view that the comprehensiveness and structure of the DISC-C can contribute to the sensitivity of the diagnostic process. PMID- 8496133 TI - The case of the confusing conference. PMID- 8496134 TI - The inpatient crunch. PMID- 8496135 TI - Debate: the effects of military life on children. PMID- 8496136 TI - A parent comments on elective mutism. PMID- 8496137 TI - A novel functional target for tumor-promoting phorbol esters and lysophosphatidic acid. The p21rac-GTPase activating protein n-chimaerin. AB - Phorbol esters are potent tumor promoters widely used for investigating mechanisms of cell transformation with protein kinase C (PKC) generally considered as being their only protein target. Lysophosphatidic acid (LPA) can act as a mitogen, affecting cell shape and the actin cytoskeleton. There is no identified functional target for LPA. We have isolated a cDNA encoding a protein n-chimaerin that is a high affinity phorbol ester receptor and a p21rac-GTPase activating protein (rac-GAP). p21rac is a member of the ras superfamily of small molecular weight GTP-binding proteins, which stimulates actin microfilament formation in Swiss 3T3 cells and superoxide production by the neutrophil oxidase. We now show that the rac-GAP activity of n-chimaerin is stimulated by phosphatidylserine (PS) and phosphatidic acid (PA) and that phorbol esters can synergize with PS and PA. LPA, in contrast, was found to inhibit n-chimaerin. The phospholipid/phorbol ester modulation of the rac-GAP activity requires the PKC like cysteine-rich domain of n-chimaerin. Thus, n-chimaerin is a novel functional target (distinct from PKC) for both phorbol esters and LPA. These data suggest that the physiological role of n-chimaerin is to link events initiating at the cell surface/membrane with p21rac effector pathways. PMID- 8496138 TI - The active site substrate specificity of the cAMP-dependent protein kinase. AB - cAMP-dependent protein kinase substrates have been synthesized employing an unusually efficient method that allows the alcohol-bearing residue to be incorporated into the peptide after solid phase peptide synthesis. These peptide substrates have been utilized to map the active site substrate specificity of the protein kinase. Only alpha- or beta-substituted alcohol-bearing residues containing the proper absolute configuration are phosphorylated by the enzyme. However, the cAMP-dependent protein kinase will phosphorylate achiral residues. The implications of the observed protein kinase substrate specificity with respect to inhibitor design are discussed. PMID- 8496139 TI - A new isoform of 11 beta-hydroxysteroid dehydrogenase in aldosterone target cells. AB - 11 beta-Hydroxysteroid dehydrogenase has been proposed to play an important role in aldosterone target cells by degrading endogenous glucocorticoids, thus allowing aldosterone to bind to the relatively nonselective mineralocorticoid receptor. The physiologically important species of this enzyme in renal aldosterone target cells appears to be kinetically and antigenically distinct from the previously characterized liver enzyme. Here we show that 11 beta-steroid dehydrogenase in the microsomal fraction of isolated renal collecting duct cells has a Km for corticosterone of 25.9 +/- 2.4 nM, about 100 times lower than the rat liver enzyme. Surprisingly, the collecting duct enzyme utilizes almost exclusively NAD as cofactor versus NADP used by the liver form. Conversion of corticosterone to 11-dehydrocorticosterone is 2.6 +/- 0.5 and 0.07 +/- 0.01 fmol/min/mg protein with 100 microM of NAD and NADP, respectively, demonstrating a 37.4 +/- 3.5-fold preference for NAD versus NADP. There is practically no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH, indicating that in collecting duct cells the enzyme operates only in the direction of oxygenation. In addition, 11 beta-steroid dehydrogenase activity is dose dependently inhibited by the end product 11-dehydrocorticosterone while the liver enzyme does not show end product inhibition. We conclude that renal collecting duct cells, the major physiological targets of aldosterone, are protected from circulating glucocorticoids by a hitherto undescribed enzyme of the 11-dehydrogenase family, which differs from the known liver enzyme in having a significantly higher affinity for corticosterone and a different cofactor requirement. PMID- 8496140 TI - Crystal structure of liganded and unliganded forms of bovine plasma retinol binding protein. AB - The three-dimensional structures of bovine plasma retinol-binding protein (bRBP) complexed with retinol (space group P2(1)2(1)2(1), a = 46.08, b = 49.12, c = 76.10 A) and of the unliganded protein prepared in vitro by extracting retinol with ethyl ether (space group P2(1)2(1)2(1), a = 46.55, b = 48.97, c = 76.87 A) have been solved at 1.9 and 1.7 A resolution, respectively. The final crystallographic R factors are 0.190 for holobRBP and 0.196 for the unliganded bRBP. The model for the bovine holoprotein is quite similar to that of the human protein, with which it exhibits 92% sequence similarity. The root mean square deviation between the alpha-carbons in the two proteins is 0.31 A. The retinol binding site is almost completely preserved. The loops that surround the opening of the beta-barrel are also particularly conserved, in contrast with the presence of several substitutions in parts of the RBP molecule opposite the opening of the calyx that binds retinol. Despite the fact that unliganded bovine RBP was prepared and crystallized using procedures completely different from those used to obtain the unliganded human RBP, the conformational differences between unliganded and liganded forms of bRBP are almost identical to those found previously between the same forms of human RBP. They mainly involve a few residues in the region extending from amino acid residues 32 to 37. Therefore, similar differences are very likely to exist between holoRBP and the physiologically occurring apoprotein. A not yet identified electron density, different in shape and orientation from retinol, also occupies the central cavity of the beta-barrel in the unliganded bRBP, as found for unliganded human RBP. The functional consequences of the conformational change induced by the removal of retinol on the interaction between RBP and transthyretin, coupled with the conservation of the entrance loops of the beta-barrel in mammalian RBPs, are consistent with their participation in molecular interactions. PMID- 8496141 TI - Alanine dehydrogenase from soybean nodule bacteroids. Kinetic mechanism and pH studies. AB - The kinetic mechanism of alanine dehydrogenase from soybean nodule bacteroids was studied by initial velocity experiments with or without product inhibitors, dead end inhibitors, or alternate substrates. Without inhibitors, double-reciprocal plots of initial velocity experiments showed intersecting lines, indicating a sequential mechanism. These initial velocity experiments also revealed rapid equilibrium ordered binding of NH4+ prior to pyruvate. When NAD was varied at changing-fixed concentrations of L-alanine, a nonlinear, concave down double reciprocal plot was obtained. Substrate inhibition by pyruvate or L-alanine with cosubstrates varied was uncompetitive giving further support to an ordered mechanism. Product inhibition studies showed that both NAD and NADH and pyruvate and L-alanine were competitive. This suggested a Theorell-Chance mechanism. When product inhibition by L-alanine was studied with NH4+ varied in a series of experiments at increasing concentrations of pyruvate, the inhibition was eliminated, as expected for a Theorell-Chance mechanism. Furthermore, when NADH, NH4+, and pyruvate were varied simultaneously, maintaining their concentrations at a constant ratio to each other, an infinite Vmax was obtained. pH studies of the kinetic parameters indicated that NH4+, rather than NH3, was the true substrate that binds to a residue on the enzyme with a pK of 8.1. In conclusion, the kinetic mechanism at pH 8.5 was determined to be a Ter-Bi Theorell-Chance. In the amination direction, the substrates add in the order: NADH, NH4+, pyruvate, with NH4+ binding in rapid-equilibrium. In the reverse direction, NAD adds first, followed by L-alanine. PMID- 8496142 TI - Refolding of luciferase subunits from urea and assembly of the active heterodimer. Evidence for folding intermediates that precede and follow the dimerization step on the pathway to the active form of the enzyme. AB - Conditions have been established that allow reversible refolding of luciferase from 5 M urea. The kinetics of formation of the active enzyme showed a concentration-independent lag, suggesting the existence of intermediate structures on the pathway of refolding. The rate of approach to the final level of activity was strongly concentration-dependent at protein concentrations below 10 micrograms/ml, but at concentrations above about 20 micrograms/ml, the rate of approach to the final activity value did not change with concentration. The concentration dependence presumably reflects the second-order step yielding the heterodimeric structure. The finding that at concentrations above 20 micrograms/ml, the rate becomes insensitive to concentration suggests that under these conditions, some step subsequent to dimerization become rate-limiting. When the refolding reaction was initiated by dilution out of 5 M urea at 50 micrograms/ml followed at various times by a secondary dilution to a final concentration of 5 micrograms/ml, it was found that the increase in activity continued at the rate characteristic of the higher protein concentration for a period of about 1-2 min following the dilution before slowing to the rate expected for the lower protein concentration. These observations indicate that there are inactive heterodimeric species that form from assembly of the individual subunits and that these species must undergo further folding to yield the active heterodimeric species. At protein concentrations of 5-50 micrograms/ml, the final yield of active enzyme was about 65-85%, decreasing at higher and lower concentrations. At higher concentrations, aggregation probably accounts for the limit in recovery, whereas at lower concentrations, it appears that the reduced yield of activity is due to the competing process of the folding of one or both individual subunits into some form incompetent to interact with each other. These experiments demonstrate the existence of slow steps in the refolding of luciferase subunits from urea and the formation of the active heterodimeric structure, both preceding and following the dimerization. Furthermore, the failure of protein at low concentrations to efficiently reassemble into the active heterodimer is consistent with the prior finding that luciferase subunits produced independently in Escherichia coli fold into conformations that cannot interact to form the active heterodimer upin mixing (Waddle, J. J., Johnston, T. C., and Baldwin, T. O. (1987) Biochemistry 26, 4917 4921). PMID- 8496143 TI - Contribution of folding steps involving the individual subunits of bacterial luciferase to the assembly of the active heterodimeric enzyme. AB - Bacterial luciferase is an alpha beta heterodimer with a single active center in which the reaction of reduced FMN, O2, and an aliphatic aldehyde yields a photon of blue-green light. We have shown that refolding of the luciferase subunits from 5 M urea occurs via the intermediacy of several species, one of which is an inactive heterodimeric structure, resulting from the dimerization of alpha and beta, which isomerizes to the active alpha beta structure in a first-order reaction (Ziegler, M. M., Goldberg, M. E., Chaffotte, A. F., and Baldwin, T. O. (1993) J. Biol. Chem. 268, 10760-10765). We have also demonstrated the existence of an inactive heterodimeric species that is well populated at equilibrium in the presence of 1.6-2.8 M urea (Clark, A. C., Sinclair, J. F., and Baldwin, T. O. (1993) J. Biol. Chem. 268, 10773-10779). We have separated the alpha and beta subunits by ion exchange chromatography and investigated the effects on reformation of active luciferase of allowing the individual subunits to refold separately prior to mixing. These investigations show that the lag in formation of active luciferase is due to slow steps in folding of the individual subunits. The beta subunit appears to fold faster than the alpha subunit, but folding of the beta subunit also shows a distinct lag. When the alpha and beta subunits were allowed to refold from urea for periods of several hours or more prior to mixing, the yield of active heterodimeric luciferase was compromised, which is consistent with the finding that individual subunits produced in vivo fold into structures incompetent to interact with each other to form the active heterodimer (Waddle, J. J., Johnston, T. C., and Baldwin, T. O. (1987) Biochemistry 26, 4917-4921). It appeared that the rate with which the beta subunit assumed the heterodimerization incompetent structure was faster than the rate with which the alpha subunit became heterodimerization-incompetent. These observations support a model for folding and assembly of the subunits of luciferase in which the two subunits fold into assembly-competent structures that associate to form the heterodimer. In a slow competing process, the subunits undergo a conformational rearrangement to form stable structures incompetent to form heterodimers. It appears that the association of the luciferase subunits might constitute an example of one polypeptide modifying the folding pathway of another, a model that is consistent with the suggestion that the formation of the heterodimeric structure of luciferase is a kinetic trap on the folding pathway of the individual subunits (Sugihara, J., and Baldwin, T. O. (1988) Biochemistry 27, 2872-2880). PMID- 8496144 TI - Folding of bacterial luciferase involves a non-native heterodimeric intermediate in equilibrium with the native enzyme and the unfolded subunits. AB - Bacterial luciferase is a heterodimeric enzyme that catalyzes the reaction of reduced FMN, O2 and an aliphatic aldehyde to yield the carboxylic acid and an excited flavin that emits blue-green light upon return to ground state. The two subunits of the luciferase from Vibrio harveyi, alpha and beta, have molecular weights of 40,108 and 36.349, respectively; the single active center resides primarily, if not exclusively, on the alpha subunit. We have found that bacterial luciferase can be unfolded in urea-containing 50 mM phosphate buffer, pH 7.0, and refolded by dilution of the urea with final luciferase concentrations of 5-25 micrograms/ml. We have analyzed the urea-induced equilibrium unfolding of bacterial luciferase by monitoring changes in both the far ultraviolet circular dichroism (predominantly secondary structure) and intrinsic fluorescence emission (predominantly tertiary structure) resulting from incubation in various concentrations of urea at 18 degrees C for 18-24 h. Both spectral methods indicated a biphasic unfolding transition; the first phase was protein concentration-independent, whereas the second phase was protein concentration dependent. Equilibrium unfolding curves showed an increase in fluorescence up to 2 M urea followed by a decrease in intensity and red shift of the emission maximum. The ratio of the fluorescence emission in the presence of 2 M urea relative to that in the absence of urea was greater when fluorescence was excited at 295 nm than at 280 nm. The fluorescence increase in the 0-2 M urea range corresponded to the first phase of the biphasic unfolding process. The urea induced loss of luciferase enzymatic activity appeared to correspond to the first transition observed with the spectroscopic methods, and likewise to be protein concentration-independent. These observations suggested a three-state unfolding mechanism in which the native heterodimeric enzyme rearranges to an inactive heterodimeric species that is well populated, followed by dissociation and unfolding of the alpha and beta subunits. The data were fit to a three-state mechanism using a nonlinear least squares method. At 18 degrees C in 50 mM phosphate, pH 7.0, the free energy change for the interconversion of the active heterodimer and the inactive heterodimeric species was estimated to be 4.52 +/- 0.30 kcal/mol; the free energy change for the interconversion of the inactive heterodimer and the individual subunits was 19.7 +/- 0.2 kcal/mol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8496145 TI - Cloning and characterization of complementary DNA encoding the eukaryotic initiation factor 2-associated 67-kDa protein (p67). AB - The eukaryotic initiation factor 2 (eIF-2)-associated 67-kDa glycoprotein (p67) protects eIF-2 alpha-subunit from inhibitory phosphorylation by eIF-2 kinases, such as heme-regulated inhibitor and double-stranded RNA-activated inhibitor. This promotes protein synthesis in the presence of eIF-2 kinases present in animal cells (Ray, M. K., Datta, B., Chakraborty, A., Chattopadhyay, A., Meza Keuthen, S., and Gupta, N. K. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 539-543). In this study, the primary structure of rat p67 is determined by cDNA cloning. Based on the partial amino acid sequences of overlapping tryptic and cyanogen bromide cleaved fragments, degenerate oligonucleotides were synthesized and used as primers for the polymerase chain reaction to amplify the corresponding p67 cDNA fragment from rat liver first strand cDNA. The amplified DNA was then used as a probe to screen a rat tumor hepatoma (KRC-7) cDNA library, and a positive clone covering the entire coding region was obtained. From the cDNA sequence, an open reading frame that encodes p67 as a 480-amino acid protein with a molecular mass of 53 kilodaltons was predicted for the unglycosylated protein. The cloned cDNA was further characterized by in vitro transcription-coupled translation in micrococcal nuclease-treated reticulocyte lysate. The translated product migrated similarly to p67 in SDS-polyacrylamide gel electrophoresis and was precipitated with antibodies against p67. Northern blot analysis of rat liver poly(A)+ RNA showed a single size class (approximately 2 kilobases) of mRNA. The deduced amino acid sequence of the protein showed a highly charged N-terminal region composed of two basic polylysine blocks and an acidic aspartic acid block. The protein also exhibits significant sequence identity in the N-terminal region with human eIF-2 beta-subunit. PMID- 8496146 TI - A novel cloning strategy reveals the gene for the yeast homologue to Escherichia coli ribosomal protein S12. AB - Using a novel technique designed to identify genes of Saccharomyces cerevisiae which carry introns, we have cloned two genes encoding ribosomal protein S28. Although the genes differ by 15 nucleotides within their coding regions, they are predicted to encode identical proteins of 145 amino acids. The predicted amino acid sequence of S28 contains significant homology to ribosomal protein S25 of Tetrahymena thermophila and to ribosomal protein S12 of several archaebacteria, suggesting a relationship to S12 of Escherichia coli. Dot matrix analysis confirmed that regions of S12, especially those implicated in the accuracy of translation, have been conserved in S28 of S. cerevisiae. Either RPS28A or RPS28B alone can support growth, but heterozygous disruption of both genes abolishes the ability to sporulate. Haploids harboring a disruption of both genes cannot survive without an intact gene on a plasmid. RPS28A maps to the right arm of chromosome VII and RPS28B to the right arm of chromosome XVI. PMID- 8496147 TI - Effects of brefeldin A and accessory proteins on association of ADP-ribosylation factors 1, 3, and 5 with Golgi. AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide binding proteins initially identified by their ability to enhance in vitro cholera toxin-catalyzed ADP-ribosylation and subsequently shown to participate in vesicular transport in the Golgi and other cellular compartments. By cDNA and genomic cloning, at least six mammalian ARFs were identified. Brefeldin A (BFA) disrupts Golgi membranes and inhibits binding of soluble high molecular weight proteins to Golgi fractions. We examined the effects of BFA on binding of ARF1, 3, and -5 to a Golgi fraction in the presence of an ATP-regenerating system and a fraction of soluble, high molecular weight, accessory proteins (SAP), presumably containing complexes identified by others as coatomers that are involved in vesicular transport. ARF binding in all instances was dependent on guanosine 5'-O (3-thiotriphosphate) and increased by the ATP-regenerating system. Binding of ARF1 and -3, but not ARF5, was enhanced by SAP. BFA inhibited the SAP-dependent, but not the SAP-independent, binding of ARF1 and -3. It had no effect on the increment in binding produced by an ATP-regenerating system. B36, an inactive derivative of BFA, did not inhibit SAP-dependent binding of ARF1 and -3. Binding of ARF5, which was SAP-independent, was not affected by BFA. These observations are consistent with the conclusion that mammalian ARFs differ in their dependence on accessory proteins for interaction with Golgi and, perhaps, other cellular membranes and that BFA specifically inhibits SAP-dependent ARF binding. PMID- 8496148 TI - Differential usage of the carboxyl-terminal region among aldolase isozymes. AB - Sequence homology among nonconserved residues 357-362 of the COOH-terminal region in fructose-1,6-bisphosphate aldolases correlates with isozyme classification of aldolases. Recombinant chimers of human liver and maize aldolases were constructed by exchanging residues 357-362 with those from muscle, maize, and liver isozyme and by insertion in the maize sequence at position 349 rabbit muscle and liver residues 346-349. Activity variation among the chimers relative to native controls ranged from less than 10% to greater than 300% of Vm. Exchange of residues 357-362 significantly affected both Vm and Km without modifying catalytic efficiency kcat/Km, whereas insertion of residues 346-349 modified Vm and Km and increased catalytic efficiency. Steady state carbanion oxidation rates varied inversely with activity and were differentially affected with respect to equilibrium oxidation rates. Sequence exchange of residues 357-362 appears to modulate carbanion proton exchange, whereas sequence insertion of residues 346 349 modifies substrate and aldehyde interaction with C6 phosphate binding locus. Low intrinsic susceptibility to carboxypeptidase A degradation of the COOH terminus in liver aldolase is consistent with tight association of this COOH terminus in a conformation unfavorable for promoting high catalytic activity. Efficient carbanion protonation promoted by specific sequences 357-362 represents a mechanistic feature which distinguishes catalytically active maize and muscle isozymes from less active liver isozyme. Conservation of active site residues among aldolases suggests that isozyme diversity among aldolases arose from divergent evolution of the COOH-terminal sequence. PMID- 8496149 TI - Selective induction by phenobarbital of the electrogenic transport of glutathione and organic anions in rat liver canalicular membrane vesicles. AB - Glutathione is excreted into bile via a low affinity, electrogenic, ATP independent transport system which is cis-inhibited and trans-stimulated by certain organic anions (Fernandez-Checa, J. C., Takikawa, H., Horie, T., Ookhtens, M., and Kaplowitz N. (1992) J. Biol. Chem. 267, 1667-1673). This transport system differs from the sinusoidal carrier in several respects, such as affinity for transport and inhibitor specificity. Another differential aspect is the selective increase by phenobarbital pretreatment of GSH excretion into bile without changing the sinusoidal release into blood. To determine if phenobarbital induces the GSH transporter in the canalicular membrane and if this is reflected in the induction of organic anion transport, we have used rat liver canalicular (cLPM) and sinusoidal (bLPM) enriched membrane vesicles from liver of control (saline) and phenobarbital-treated rats. cLPM vesicles prepared from phenobarbital-pretreated rats exhibited a significant, 46% increase in Vmax for transport (9.02 +/- 0.3 versus 6.17 +/- 0.5 nmol/mg/15 s) without a change in the Km for GSH transport (14.0 +/- 1.1 versus 16.7 +/- 2.7 mM, respectively). Kinetic parameters for GSH transport in bLPM vesicles remained unchanged after phenobarbital treatment versus control (Vmax, 4.67 +/- 0.2 versus 4.77 +/- 0.2 nmol/mg/15 s; Km, 7.79 +/- 0.8 versus 6.95 +/- 0.8 mM, respectively). Phenobarbital treatment increased the electrogenic transport of [35S]sulfobromophthalein (BSP) (5 and 50 microM) but not the electrogenic uptake of [14C] glycocholic acid (10 and 200 microM). In addition, the ATP-dependent transport of [35S]BSP, [3H]leukotriene C4, and [14C]glycocholic acid into cLPM vesicles was not altered by phenobarbital treatment. The ATP-independent transport of [35S]BSP in cLPM was cis-inhibited and trans-stimulated by GSH, supporting the view that BSP and GSH share a common multispecific transporter. Thus, among the various canalicular transport systems, the multispecific electrogenic organic anion and GSH transport system is selectively induced by phenobarbital treatment. PMID- 8496150 TI - Kinetic studies on benzyl alcohol dehydrogenase encoded by TOL plasmid pWWO. A member of the zinc-containing long chain alcohol dehydrogenase family. AB - The nucleotide sequence of the structural gene for benzyl alcohol dehydrogenase encoded by TOL plasmid pWWO of Pseudomonas putida has been determined. Benzyl alcohol dehydrogenase is a member of the long-chain zinc alcohol dehydrogenase family and, like other alcohol dehydrogenases of this family, contains two zinc atoms per subunit. Benzyl alcohol dehydrogenase, while sharing 31% identical residues with horse liver alcohol dehydrogenase, contains several amino acid substitutions near the active site, some of which may be responsible for the substrate specificity of benzyl alcohol dehydrogenase, which oxidizes exclusively aromatic substrates. Benzyl alcohol dehydrogenase also notably lacks the His51 residue of horse liver alcohol dehydrogenase. Contrary to the results obtained with a mutant human liver alcohol dehydrogenase lacking this residue, the concentration and pKa of solvent proton acceptors had no effect on the catalytic efficiency of benzyl alcohol dehydrogenase. The electronic nature of substituents on the aromatic ring of the substrate influenced the kcat of the enzyme in low concentrations of external proton acceptor, but not in high concentrations. Product inhibition studies demonstrated that benzyl alcohol dehydrogenase followed a general Ordered Bi Bi kinetic mechanism in low proton acceptor conditions, while following a Theorell-Chance kinetic mechanism at high proton acceptor conditions. PMID- 8496151 TI - Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. AB - PC cell line is a highly tumorigenic insulin-independent variant from the teratoma-derived adipogenic cell line 1246. Culture medium of PC cells contains a growth promoting activity for 3T3 cells and producer cells. PC cell-derived growth factor (PCDGF) was purified to homogeneity from PC cell-conditioned medium as an apparent 88-kDa protein by chromatography on heparin-Sepharose, Sephacryl S 200, and phenyl-Sepharose. Digestion with peptide-N-glycosidase F yielded an apparent 68-kDa protein component indicating that PCDGF is a glycoprotein containing about 20 kDa of carbohydrate. Partial sequence from Edman degradation of peptide fragments obtained by digestion of PCDGF with cyanogen bromide and trypsin demonstrates that PCDGF contains regions of sequence identity to that deduced from the granulin or epithelin precursor cDNAs. Granulins are small polypeptides purified from granulocyte extracts with no apparent biological functions. Epithelins are cell growth modulators purified as small molecular mass 6-kDa polypeptides from kidney extracts. The existence of a large molecular mass precursor for granulin or epithelin has been predicted based upon recently cloned cDNAs encoding these biomolecules within a 63.5-kDa protein with putative glycosylation sites. No biological activity has previously been attributed to the precursor. The present results indicate that PCDGF is a potential precursor for epithelin and/or granulin, that this 88-kDa protein is secreted and glycosylated, and that it can function as a mitogen for 3T3 cells as well as an autocrine growth factor for PC cells. PMID- 8496152 TI - Calcium ionophore-induced transient down-regulation of c-myb mRNA levels in Friend erythroleukemia cells. AB - The effects of calcium ionophores A23187 and ionomycin on the c-myb and c-myc mRNA levels have been investigated in the Friend erythroleukemia cell line F4-6 using Northern blot analysis. Treatment of the cells with 0.5-4 microM A23187 or 1-4 microM ionomycin induced a concentration-dependent decrease in c-myb mRNA; this decrease was abolished by EGTA. c-myc mRNA levels were only moderately affected. After 12-24 h of calcium ionophore exposure, c-myb mRNA returned to pretreatment levels. No similar decrease in c-myb mRNA was seen with the sodium ionophore monensin (up to 16 microM). The dimethyl sulfoxide-induced suppression of c-myb and also of c-myc mRNA levels was not prevented in Ca(2+)-free medium and thus appeared Ca(2+)-independent. A23187 and ionomycin were capable of inducing beta-globin mRNA synthesis in F4-6 cells. Prolonged calcium ionophore exposure, however, strongly reduced cell viability and resulted only in a slight hemoglobin increase at lower concentrations. These results suggest that a rise in [Ca2+]i may be a signal leading to a transient decrease in c-myb mRNA and the initiation of erythroid differentiation in Friend cells. The transient suppression of c-myb mRNA levels represents a common feature of the action of dimethyl sulfoxide and calcium ionophores. PMID- 8496153 TI - Mapping of nidogen binding sites for collagen type IV, heparan sulfate proteoglycan, and zinc. AB - Recombinant nidogen fragments comprising the globular domains G1 plus G2, the rod like domain, and the rod connected to the globe G3 were prepared from the culture media of transfected human cell clones. In addition, domains G1 and G2 were separated from each other after cleavage with chymotrypsin. The purified fragments were characterized by N-terminal sequences, electrophoresis, electron microscopy, and radioimmunoassays and the cell clones by Northern hybridization. Transfection with a construct comprising a large part of domain G3 showed high mRNA levels but no secreted protein, indicating a protein folding problem. All these fragments were used as soluble and/or immobilized ligands in binding assays. This demonstrated major binding sites on domain G2 for collagen IV and heparan sulfate proteoglycan. Affinity chromatography on zinc- and cobalt-loaded columns showed binding of domains G2 and G3 and the rod. Protein binding, but not metal binding, was abolished by reduction and alkylation of nidogen. This allowed for the isolation of several zinc-binding tryptic peptides, four from G2, two from the rod, and one from the G3 domain. Most of these short peptides contained several histidines that are likely to mediate binding. Zinc inhibited efficiently G3-mediated nidogen binding to laminin at 4 degrees C (IC50 approximately 5 microM) but less at higher temperatures. Similarly, zinc inhibited binding to collagen IV and proteoglycan at low temperatures but not at high (37 degrees C) temperatures. This indicates a complex modulation of nidogen binding to other basement membrane proteins by some, but not all, transition metals. Whether the particularly striking effects shown for zinc are of biological relevance remains to be established. PMID- 8496154 TI - Identification of a novel subunit of the type I interferon receptor localized to human chromosome 21. AB - Expression in mouse cells of the cloned human IFN alpha receptor (IFN alpha R) subunit selectively confers response and binding to human IFN alpha 8, indicating that other subunits are involved in IFN alpha binding. We report here that a new monoclonal antibody (mAb), termed IFNaR beta 1, recognizes a novel IFN alpha R subunit different from the one recently cloned and distinct from the alpha subunit recognized by the IFN alpha R3 mAb. The IFNaR beta 1 mAb blocks the biological effect of seven different Type I IFNs. Immunoprecipitations after cell surface iodination demonstrate that the IFNaR beta 1 mAb recognizes a protein with a molecular mass of 100 kDa in Daudi and U-266 cells that express normal IFN alpha R. However, a 55-kDa protein instead of the 100-kDa product was immunoprecipitated in the IFN alpha-resistant U-937 cell line that express the variant form of the receptor. We also demonstrate that the gene that codes for this novel IFN alpha R subunit maps to human chromosome 21, as do the cloned IFN alpha R subunit and the alpha subunit, indicating the existence of a locus on this chromosome that regulates binding for Type I IFNs. PMID- 8496155 TI - Structure-function studies of the human thyrotropin receptor. Inhibition of binding of labeled thyrotropin (TSH) by synthetic human TSH receptor peptides. AB - We have probed the hormone binding regions of the entire putative extracellular domain of the human thyrotropin (TSH) receptor (hTSHr) using synthetic peptides. A series of 26 overlapping peptides comprising the complete sequence of the extracellular domain of hTSHr was synthesized. Each peptide (20 amino acid residues each) was tested for its ability to interact with TSH, as evidenced by inhibition of binding of labeled hormone to native, membrane bound TSH receptors. Four of the 26 peptides interacted with labeled TSH and inhibited its binding to thyroid membranes. The most potent of these peptides was 256-275, which inhibited 125I-bovine TSH binding with an IC50 of 31.7 +/- 1.3 microM. The remaining peptides were 16-35 (351 +/- 9.4 microM), 106-125 (282 +/- 20.5 microM), and 226 245 (951 +/- 245 microM). An additional peptide, 286-305, showed minimal activity, and the remaining 21 peptides showed no activity. Peptides 256-275, 106 125, and 16-35 also inhibited binding of 125I-human chorionic gonadotropin to ovarian membrane receptors, suggesting that those regions of the receptor are involved in binding of a common glycoprotein hormone structure such as the alpha subunit. In contrast, peptides 226-245 and 286-305 did not inhibit human chorionic gonadotropin binding, suggesting that these two regions are involved in hormone-specific activity. Of interest is the finding that the latter two peptides are from regions of TSHr that are largely dis-homologous to the lutropin receptor, whereas the former three, with the exception of 16-35, are from regions that are largely homologous between the two receptors. The data suggest that multiple, discontinuous regions of the extracellular domain of hTSHr are involved in the binding of the hormone. Furthermore, the binding regions are localized to TSHr-specific sequences as well as to regions that are highly homologous to LHr. This suggests that homologous regions of the two receptors are likely to perform similar functions in the interaction with their specific hormone, suggesting that those regions may be involved in binding of the glycoprotein hormone common alpha subunit. PMID- 8496156 TI - Interaction of GTPase activating proteins (GAPs) with p21ras measured by a novel fluorescence anisotropy method. Essential role of Arg-903 of GAP in activation of GTP hydrolysis on p21ras. AB - Ras GTPase activating proteins (GAPs) contain an invariant motif, -FLR-, within the most conserved region of their catalytic domains. Certain mutations in this motif have greatly reduced activity (Skinner, R. H., Bradley, S., Brown, A. L., Johnson, N. J., Rhodes, S., Stammers, D. K., and Lowe, P. N. (1991) J. Biol. Chem. 266, 14163-14166), but it was not determined whether the reduced activity was due to loss of binding or impaired catalysis. In order to address this question, we have developed a simple physical method to study formation of GAP.p21ras complexes. This utilizes the increase of fluorescence anisotropy upon binding of GAP to p21ras complexed with 2'(3')-O-(N-methylanthraniloyl) (mant) derivatives of guanine nucleotides. Dissociation constants obtained for the catalytic domains of either p120-GAP (GAP-344) or neurofibromin (NF1-GRD) with normal and Leu-61 p21ras proteins are comparable with those obtained by kinetic methods. In the course of these studies, we found, in contrast to previous observations, that both GAP and NF1-GRD can weakly activate the GTPase of Leu-61 mutant p21, showing that Gln-61 is not absolutely required for the stimulation of GTPase activity by GAPs. The fluorescence anisotropy method allowed us to show that mutation of Arg-903, within the FLR motif of GAP, can result in protein defective in catalysis but not in binding to p21ras. These data suggest a direct role for this residue in catalyzing GTP hydrolysis on p21ras, possibly by contributing a catalytic group to the p21 active site. This method is independent of the catalytic activity of the proteins, and so it could be extended generally to the measurement of binding of effector molecules, exchange factors, or other macromolecules to guanine nucleotide-binding proteins. PMID- 8496157 TI - Structure-function analysis of the Bcl-2 oncoprotein. Addition of a heterologous transmembrane domain to portions of the Bcl-2 beta protein restores function as a regulator of cell survival. AB - The bcl-2 gene can potentially encode 26- and 22-kDa proteins that differ only in their carboxyl tails because of an alternative splicing mechanism. The larger of these proteins contains a hydrophobic transmembrane domain within its carboxyl terminus, resides (at least in part) in mitochondrial membranes and has been shown to prolong cell survival by blocking programmed cell death (also termed "apoptosis"). To explore the function of the shorter 22-kDa Bcl-2 protein that lacks a transmembrane domain, DNAs encoding p26-Bcl-2-alpha or p22-Bcl-2-beta were expressed in an interleukin-3 (IL-3)-dependent hematopoietic cell line 32D. In contrast to p26-Bcl-2 alpha that markedly prolonged cell survival, p22-Bcl-2 beta did not extend the survival of 32D cells when cultured in the absence of IL 3. Expression in 32D cells of a chimeric DNA that fused portions of the open reading frame common to Bcl-2-alpha and Bcl-2-beta (amino-acids 1-195) with sequences encoding the transmembrane and cytosolic domains of the IL-2 receptor alpha protein resulted in production of a Bcl-2/IL-2R fusion protein that was capable of prolonging 32D cell survival in the setting of IL-3 withdrawal. Based on fractionation of cells to produce crude heavy membrane, light membrane, nuclei, and cytosolic preparations, much of the p22-Bcl-2-beta protein appeared to reside in the cytosol, whereas Bcl-2-alpha and the Bcl-2/IL-2R chimeric proteins were found exclusively in fractions that also contained the inner mitochondrial membrane protein F1-beta-ATPase. Taken together, these findings demonstrate the importance of membrane association for the function and intracellular targeting of the apoptosis-blocking Bcl-2 protein. Furthermore, despite the strong evolutionary conservation of the carboxyl regions of Bcl-2 alpha proteins observed previously for mammalian and avian species, these data suggest that a heterologous transmembrane domain can be substituted without loss of function. PMID- 8496158 TI - Mannosamine inhibits the synthesis of putative glycoinositol phospholipid anchor precursors in mammalian cells without incorporating into an accumulated intermediate. AB - Mannosamine (ManN) has been reported to inhibit the formation of Man alpha-1,2Man linkages and to prevent the anchoring of membrane proteins by glycoinositol phospholipids (GPIs). In this paper, the effect of ManN on the synthesis of putative GPI anchor precursors in mammalian cells was studied. Three different cell lines were analyzed: HeLa cells and Thy-1 negative lymphoma mutants B and F that accumulate two-mannosyl GPI (Man2GPI) and three-mannosyl GPI (Man3GPI) species, respectively. ManN did not alter the incorporation of [3H]Man into the Man2GPI in mutant B cells. However, when either HeLa cells or mutant F cells were labeled with [3H]Man in the presence of ManN, [3H]Man incorporation into Man3GPi species was blocked and the TLC profile of [3H]Man-labeled glycolipids resembled that obtained with mutant B cells. Further characterization of the predominant labeled glycolipid that accumulated in ManN-treated HeLa cells by enzymatic and chromatographic criteria and permethylation analysis confirmed the structure as a Man2GPI indistinguishable from the Man2GPI that accumulates in mutant B cells. Based on previous reports that ManN inhibits Man alpha-1,2Man linkage formation and that in GPI-anchored proteins the third Man residue is attached by a Man alpha-1,2Man linkage, these results indicate that the third Man residue that distinguishes the putative Man2GPI precursor from the Man3GPI precursor also is attached by a Man alpha-1,2Man linkage. Furthermore, the observation that Man2GPI rather than a new GPI species containing ManN accumulated during ManN treatment revealed that the mechanism of ManN inhibition primarily involved inhibition of an alpha 1,2-mannosyltransferase rather than incorporation of ManN into an aberrant GPI species. PMID- 8496159 TI - Ca2+ binding to sarcoplasmic reticulum ATPase revisited. I. Mechanism of affinity and cooperativity modulation by H+ and Mg2+. AB - H+ and Mg2+ are known to inhibit Ca2+ binding to the transport sites of sarcoplasmic reticulum-ATPase. Evaluation of the affinity for the Ca2+ binding sites requires measurement of the amount of Ca2+ bound to ATPase as a function of the free Ca2+ concentration imposed by a Ca2+ chelator. The choice of the chelator is crucial as it determines the accuracy of the free Ca2+ concentration. At pH > 7, the EGTA affinity for Ca2+ is higher than that of ATPase, inducing artifacts that alter the shape of the binding curves. Thus, we have used 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), whose affinity is unchanged at pH > or = 7. Ca2+ binding was studied at equilibrium, from pH 6 to pH 8 and from 0 to 10 mM Mg2+, using EGTA and/or BAPTA and [45Ca]Ca2+. Under all conditions, the stoichiometry was 2 Ca2+/ATPase. At variance with previous studies, the Hill coefficient was 1.1-2 and higher at pH 6 than at pH 8. In addition, it decreased in the presence of Mg2+. The Ca2+ binding curves were analyzed according to a model in which they result from a sequential binding of two Ca2+, each binding step being modified by H+ and Mg2+. The effect of H+ is described by two steps involving two H+ and one H+, with pK 7 and 7.9, respectively. At pH 6, ATPase must lose two H+ for the first Ca2+ to bind and a third H+ for the second Ca2+ to bind. At pH 9, both Ca2+ bind without any H+ exchange. Mg2+ can bind to all species, except to that saturated with Ca2+. The species having lost two H+ has a higher affinity for Mg2+ (< or = 1 mM) than the species having bound three H+ (4 mM). The above model allows us to analyze the effects of H+ and Mg2+ at each Ca2+ binding step and to explain the changes in the apparent affinity and cooperativity. PMID- 8496160 TI - Ca2+ binding to sarcoplasmic reticulum ATPase revisited. II. Equilibrium and kinetic evidence for a two-route mechanism. AB - The experiments reported in the present paper were designed to check the model proposed for Ca2+ binding in the preceding paper (Forge, V., Mintz, E., and Guillain, F. (1993) J. Biol. Chem. 268, 10953-10960). The pH dependence of the Mg(2+)-induced variation of the intrinsic fluorescence, as well as that of the phosphorylation by Pi, confirmed that there are several species of Ca(2+) deprived ATPase. Kinetics of Ca2+ binding as a function of pH suggested that the deprotonated form of the ATPase binds Ca2+ rapidly (k > 50 s-1), whereas the protonated forms bind Ca2+ slowly (1.3-2.7 s-1). At variance with other models which are linear, slow and rapid Ca2+ binding take two different routes, and intermediate pH values and Mg2+, which favors the deprotonated forms, result in biphasic kinetics. Mg2+ binds to all Ca(2+)-deprived species and to species having one bound Ca2+ but does not bind to ECa2. This is the reason why Mg2+ inhibits Ca2+ binding, and this inhibition is removed in the presence of adenosine-5'-O-(3-thiotriphosphate) which drives Mg2+ into the catalytic site. PMID- 8496161 TI - Binding and regulatory properties of expressed functional domains of chicken gizzard smooth muscle caldesmon. AB - We expressed the following fragments of chicken gizzard caldesmon in the pMW 172/BL21 (DE3) system at 0.4-2.2 mg of pure protein/liter of culture: full-length smooth muscle caldesmon (CDh) (amino acids 1-756), nonmuscle caldesmon (CDl), amino acids 1-128 (N128), 1-578 (N578), 230-419, 606-756 (606C), and 658-756 (658C). CDh bound tropomyosin with a Kd of 1.5 microM; N578, 230-419, and 606C bound with affinities at least 2-5 fold lower; N128 bound weakly; and 658C did not bind. Only N128 and N578 bound to smooth muscle myosin, both about 10-fold weaker than CDh and CDl. Only 606C and 658C bound to actin-tropomyosin with affinities CDh = 606C > 658C. The binding to actin-tropomyosin was biphasic, whereas the binding to actin was monophasic, corresponding to the weak binding component found in the presence of tropomyosin. Calmodulin bound only to the C terminal fragments with the same affinity as CDh. CDh, 606C, and 658C inhibited actin-tropomyosin-activated myosin ATPase, with maximal inhibition correlated with 1 caldesmon bound/14 actins, and inhibition was reversed by Ca(2+) calmodulin. Thus, the actomyosin ATPase regulatory function, calmodulin binding, and most actin binding is located within the C-terminal 99 amino acids, whereas tropomyosin binding is distributed throughout the rest of the molecule. PMID- 8496162 TI - Transient transfection studies of secretion in bovine chromaffin cells and PC12 cells. Generation of kainate-sensitive chromaffin cells. AB - We have developed a transient transfection method to measure protein secretion from non-dividing, primary bovine chromaffin cells and from the continuous cell line, PC12. A plasmid coding human growth hormone (GH) was expressed in sufficient amounts in bovine chromaffin and PC12 cells to allow precise measurements of secretion from the small fraction (less than 1%) of transfected cells in a dish. GH was secreted in a similar proportion to endogenous catecholamine upon nicotinic stimulation, depolarization with elevated K+, and upon permeabilization with digitonin and subsequent stimulation with micromolar Ca2+. GH in homogenates from GH-transfected chromaffin cells cosedimented with catecholamine on discontinuous sucrose gradients. The data indicate that transiently expressed human GH in chromaffin and PC12 cells is localized predominantly in secretory vesicles in the regulated secretory pathway. With transient transfection there is a high probability of coexpression in the same cell of two plasmids which are cotransfected. Coexpression of a plasmid for GH and a plasmid for the non-N-methyl-D-aspartate glutamate receptor, GluR1, created chromaffin cells in which Ca(2+)-dependent GH secretion could be stimulated by the glutamatergic agonist kainate. The ability to coexpress a plasmid of interest with a plasmid for GH will allow the investigation of the role of other cloned proteins in the regulated secretory pathway in differentiated, non-dividing cells. PMID- 8496163 TI - Regulation of linkages between the erythrocyte membrane and its skeleton by 2,3 diphosphoglycerate. AB - In addition to reducing hemoglobin-O2 affinity, 2,3-diphosphoglycerate (DPG) is known to modulate the mechanical properties of the erythrocyte membrane. By fluorescence spectroscopy and differential scanning calorimetry, we demonstrate that DPG binds the cytoplasmic domain of erythrocyte membrane band 3 in two stages characterized by apparent KD values of approximately approximately 2 and 12 mM. DPG was also shown to perturb the stability of ankyrin, protein 4.1, and protein 4.2 in situ and to directly bind to protein 4.1. In studies of membrane skeleton interactions, DPG was observed to inhibit the fast and slow phases of ankyrin binding to band 3 and to reduce both the number of ankyrin sites and affinity of ankyrin for each class of site. The inhibition was biphasic, similar to the band 3-DPG binding isotherm; however, at physiological DPG concentrations a reduction in only 15% of the ankyrin sites was observed. In contrast, inhibition of protein 4.1 binding to the membrane reached 65% at physiological DPG concentrations (approximately approximately 5.9 mM); at more elevated concentrations, blockade was nearly quantitative, affecting glycophorin and band 3 sites alike. Taken together with previous observations, these data suggest that DPG's effect on O2 delivery may extend beyond its well recognized impact on hemoglobin-O2 affinity. PMID- 8496164 TI - Mutational analysis of the human DNA polymerase alpha. The most conserved region in alpha-like DNA polymerases is involved in metal-specific catalysis. AB - Five site-directed mutations were introduced at the most conserved amino acids in region I (YGDTDS) of the human DNA polymerase alpha catalytic subunit. Mutant proteins were expressed in the baculovirus system by an improved method and purified by a rapid one-step purification in high yield and high specific activity. The Asp1004 to Asn mutation produced a protein with no detectable polymerase activity while other mutations gave activities from 1 to 20% of the wild type polymerase activity. Steady state kinetic analysis of the active mutants indicates that none of the mutations caused a change in Km(dNTP) or KD(DNA), but all active mutants showed a decrease in kcat. Thus, the effect of these conserved mutations is manifest in altered rates of catalysis. Two mutations, Asp1002 to Asn and Thr1003 to Ser, caused the enzyme to utilize Mn2+ more effectively in catalysis than Mg2+, suggesting that these amino acids are involved in metal binding. Rates of catalysis by the D1002N and T1003S mutants, as well as Y1000F mutant were improved 80-, 30-, and 70-fold, respectively, on homopolymer templates when Mn2+ replaced Mg2+ as the activator metal. The results from these mutational studies suggest that this highly conserved region binds the metal which is essential for catalysis. The Asp1002 may participate directly in chelating the metal. Results from the T1003S mutant suggest that the beta-methyl group of the threonine side chain might be locked in a hydrophobic pocket preventing free rotation around the C alpha-C beta bond, thus positioning the Thr1003 hydroxyl group to form a crucial bond with the metal ion. In addition, D1002N and T1003S displayed a 20-fold resistance to aphidicolin compared to the wild type polymerase alpha, and all of the active mutants displayed altered sensitivity to butylphenyl-dGTP. Models of the involvement of region I in catalysis and aphidicolin interaction are proposed. The mutational studies presented in this report will serve as a prototype for the functional role of region I in catalysis for all alpha-like DNA polymerases. PMID- 8496165 TI - Fidelity studies of the human DNA polymerase alpha. The most conserved region among alpha-like DNA polymerases is responsible for metal-induced infidelity in DNA synthesis. AB - Mutational studies in the highly conserved region I domain of the human DNA polymerase alpha enzyme demonstrated a change in metal cation-specific catalysis. Here, we extend the investigation to include the fidelity of DNA synthesis by these mutants, studying misinsertion, mispair extension, and the nucleotide analog utilization. The fidelity of region I mutants and wild type human DNA polymerase alpha enzyme were analyzed with either Mg2+ or Mn2+ as the metal activator. Despite the known mutagenic effect of Mn2+ in causing polymerases to misinsert nucleotides and to utilize dideoxynucleotides, we have found that two region I mutants, D1002N and T1003S, which utilize Mn2+ in catalysis more effectively than Mg2+, actually have a 70- and 40-fold higher misinsertion fidelity, respectively, in Mn(2+)-catalyzed reactions than that of the wild type enzyme. The enhanced misinsertion fidelity of these two mutants in Mn(2+) catalyzed reactions is due to Km discrimination of the incorrect nucleotide where the D1002N and T1003S had a 850- and 62-fold higher Km for insertion of incorrect than correct nucleotide, respectively. In Mg(2+)-catalyzed reactions, all of the region I mutants exhibited similar misinsertion efficiencies as the wild type polymerase. Study of mispair extension showed that in Mn(2+)-catalyzed ractions, the wild type polymerase alpha enzyme readily extended mispair termini. In contrast, the two region I mutants, D1002N and T1003S, were unable to extend the mispaired termini in either Mg(2+)- or Mn(2+)-catalyzed reactions. These results suggest that the side chains of region I amino acids play an essential role in the Mn(2+)-induced infidelity during DNA synthesis by human DNA polymerase alpha. The effects of the metal activator on the utilization of two nucleotide analogs, 3'-azido-3'-deoxythymidine triphosphate and ddCTP, by the region I mutants were also investigated. PMID- 8496166 TI - A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. AB - A clone, designated pag, was isolated by differential screening of cDNA libraries made from the untransformed and ras-transformed human mammary epithelial cell line HBL100. This cDNA corresponds to a gene constitutively expressed in most human cells which is induced to higher levels upon serum stimulation in untransformed and ras-transformed HBL100 cells. However, the abundance of the pag transcript is approximately 3-fold higher in transformed as compared to untransformed cells after 7-15 h of serum stimulation. In the promyelocytic leukemia cell line HL60 induced to differentiate the level of pag mRNA starts to decrease between 48 and 72 h following induction. During this period, which represents the commitment phase of differentiation, HL60 cells cease to proliferate. Therefore, in HBL100 and HL60 cells, higher levels of pag gene expression are correlated with cell proliferation. The pag cDNA codes for a 22 kDa protein, devoid of known consensus motifs, and shares 66% homology with a murine gene product (MER5) that is preferentially expressed in erythroleukemia cells during the early period of cell differentiation. In addition, the pag gene product shares approximately 50% identity with a 29-kDa surface antigen of Entamoeba histolytica and a 26-kDa antigen of Helicobacter pylori. Distant relationship was also found with other prokaryotic proteins. The pag cDNA hybridizes to multiple sequences within human and other mammalian genomes and to fewer sequences in chicken and Saccharomyces cerevisiae. Although a true relationship between eukaryotic and prokaryotic genes is difficult to establish, the conservation of pag gene sequences throughout Eukaryotae rather suggests that the pag locus belongs to a new class of genes encoding highly conserved proteins. PMID- 8496167 TI - Botulinum toxin inhibits arachidonic acid release associated with acetylcholine release from PC12 cells. AB - The molecular mechanisms of depolarization-induced calcium-dependent acetylcholine (ACh) release and its inhibition by botulinum neurotoxin type A (BoTx) are not clear. We studied these mechanisms in an in vitro cholinergic neuronal pheochromocytoma PC12 cell line model. Cultured monolayer PC12 cells were differentiated by treatment with 50 ng/ml nerve growth factor (NGF) for 4 days to enhance cellular ACh synthesis and release. Stimulation of these cells with high K+ (80 mM) in the perfusion medium caused a marked increase (three to four times) in [3H]ACh release in a Ca(2+)-dependent manner. K(+)-stimulated [3H]ACh release was totally inhibited by pretreatment of cells with BoTx (2 nM) for 2 h. High K+ also stimulated the release of arachidonic acid ([3H]AA) from the cell membrane, which was inhibited by BoTx (2 nM). Addition of phospholipase A2 (PLA2) inhibitors (quinacrine, 4-bromophenacyl bromide, manoalide) to the perfusion medium inhibited K(+)-stimulated [3H]ACh and [3H]AA release in a dose dependent manner. Inclusion of exogenous AA, the PLA2 activator melittin, or PLA2 itself prevented the effect of BoTx. These results demonstrate that in NGF differentiated PC12 cells, AA release is associated with ACh release, BoTx inhibits both processes, and increased AA can protect against BoTx. PMID- 8496168 TI - Regulation by membrane potential of phosphatidylinositol hydrolysis in pancreatic islets. AB - In pancreatic islets stimulated with carbamylcholine (carbachol), hydrolysis of both phosphatidylinositol (PtdIns) and phosphatidylinositol bisphosphate (Ptd InsP2) occurs and can be measured as the inositol monophosphates Ins(1)P1, or Ins(4)P1, respectively (Biden, T. J., Prugue, M. L., and Davison, A. G. M. (1992) Biochem. J. 285, 541-549). Our current aim was to establish whether these two events were independently regulated. Rats islets were labeled with either [3H]inositol or [3H]arachidonic acid for measurement of InsP1s by high performance liquid chromatography or diacylglycerol by TLC, respectively. The rise in Ins(1)P1 due to carbachol (1 min) was inhibited by 50% by concomitantly raising extracellular KCl ([K+]e) from 6 to 30 mM, thereby depolarizing the islets. Similar results, obtained in the absence of extracellular Ca2+, exclude the involvement of voltage-gated Ca2+ channels. Conversely, hyperpolarization, by lowering [K+]e to 3 mM, increased by 30% the rise in Ins(1)P1. In fact, over the [K+]e range of 3 to 48 mM, stimulated Ins(1)P1 accumulation was directly proportional to the calculated membrane potential. In contrast, raising [K+]e from 6 to 48 mM exerted no significant effect on carbachol-stimulated Ins(4)P1 levels, and both Ins(1)P1 and Ins(4)P1 were unaffected in the absence of carbachol. The rises in Ins(1)P1 (but not Ins(4)P1) were also inhibited by depolarization with the sodium pump inhibitor, ouabain, or the K+ channel blocker, tolbutamide. Stimulated diacylglycerol accumulation and insulin secretion (20 min) showed a biphasic dependency on [K+]e, being less pronounced at 6 mM than at either 3 or 30 mM KCl. This reflects a selective potentiation of PtdIns and PtdInsP2 hydrolysis, due, respectively, to hyperpolarization and the gating of voltage-dependent Ca2+ channels. The differential regulation of these two hydrolytic events is probably important for independent control of the activation of protein kinase C and Ca2+ mobilization and might play a role in modulating the secretory response in vivo. PMID- 8496169 TI - Characterization of glycoprotein II from bovine adrenal medullary chromaffin granules. Identification of components representing the secretory vesicle counterparts of the lysosomal-associated membrane glycoproteins (lamp-1 and lamp 2). AB - Glycoprotein II (GpII) is a heterogenous glycoprotein isolated from the membranes of bovine chromaffin granules in the adrenal medulla. When viewed by two dimensional electrophoresis this glycoprotein consists of two components, upper (GpIIa) and lower (GpIIb), with a molecular mass of 80,000-100,000 daltons and a pI of 4.2-4.7. NH2-terminal sequence analysis of GpIIa and GpIIb revealed sequence similarity with lysosomal membrane glycoproteins (lamp-1 and lamp-2), which was supported by sequence data of peptides from trypsin and cyanogen bromide digestions. An oligonucleotide probe was used to isolate a cDNA clone encoding the nucleotide sequence of GpIIa. The predicted amino acid sequence of GpIIa shares a 72% identity with the human lamp-1 type protein, which belongs to a highly conserved group of lysosomal-associated membrane glycoproteins (lamp proteins), whose function is still unknown. The COOH-terminal region of GpIIa was identical to the COOH-terminal region of lamp proteins. This COOH-terminal determinant has been demonstrated to be essential for the intracellular targeting of lamp proteins to lysosomes. A synthetic peptide antisera to the COOH-terminal region of GpIIa was used to show that this region is present on purified chromaffin granules and not proteolytically processed. The sequence analysis of GpIIa and immunological data confirm GpII as the secretory granule counterpart of lamp proteins and raise some questions regarding intracellular targeting between lysosomes and secretory granules within the chromaffin cell. PMID- 8496170 TI - Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5 beta cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestanoic acid. AB - The sequence of reactions catalyzed by sterol 27-hydroxylase (CYP27) in the oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid was studied with apparently homogeneous preparations of the cytochrome P-450 from rabbit liver mitochondria. Conditions are described for the formation and characterization of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al as an enzymatically generated intermediate in the oxidation process. Incubation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol or 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol with sterol 27-hydroxylase in 18O2 atmosphere resulted in the incorporation of one or two 18O atoms in the carboxyl group of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestanoic acid. Similar incubations with 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al resulted in the incorporation of one 18O atom in the 27 carboxyl group. The results strongly indicate that the sterol 27-hydroxylase performs multiple monooxygenations in the conversion of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestanoic acid. The following reaction sequence (Reaction 1) at carbon 27 is proposed. [formula: see text] Reaction 1. PMID- 8496171 TI - Circular dichroism studies of diethyl pyrocarbonate-modified histidine in hen egg white lysozyme. AB - The single histidine residue (His-15) in hen egg white lysozyme (EC 3.2.1.17) was chemically modified by diethyl pyrocarbonate (DEPC) to form exclusively the mono N-carbethoxyimidazole adduct (second order rate constant of 252 +/- 16 M-1 min 1). Irreversible biscarbethoxylation of the His-15 imidazole ring by DEPC was observed when lysozyme was pretreated with 2-mercaptoethanol (2-ME), 2-ME plus 8 M urea, or 2-ME plus 1% (w/v) sodium dodecyl sulfate (SDS). Circular dichroism difference spectra were measured for the mono-N-carbethoxyimidazole derivatives of lysozyme, N alpha-acetyl-L-histidine, angiotensin-II, and O-carbethoxy-N alpha acetyl-L-tyrosine. The circular dichroism difference spectrum for mono-N carbethoxy lysozyme had one main band (delta [theta]244 nm = +17,000 degree. cm2.dmol-1) in the 240-260 nm region. Denaturing mono-N-carbethoxy lysozyme with 2-ME and 8 M urea (55 degrees C) or 1% SDS (100 degrees C) essentially abolished its circular dichroism difference spectrum in the 240-260 nm region without any decarbethoxylation. In this same region the circular dichroism difference spectra of DEPC-modified N alpha-acetyl-L-histidine and DEPC-modified angiotensin-II had two much weaker bands (delta [theta]233 nm = +1000 degree.cm2.dmol-1 and delta[theta]252nm = -600 degree.cm2.dmol-1 for N alpha-acetyl-L-histidine). This study reports the first characterization of circular dichroism associated with mono-N-carbethoxyhistidine in an enzyme (lysozyme), a peptide (angiotensin-II), and a model compound (N alpha-acetyl-L-histidine). PMID- 8496172 TI - Topography of glycosylation and UDP-xylose production. AB - In order to define the location and organization of the numerous reactions involved in polysaccharide assembly during synthesis of proteoglycans and glycoproteins, the topography of some of the glycosylation reactions in chondroitin sulfate synthesis was examined using a relatively new technique for generating permeable cells. Permeable chondrocytes were shown to directly take up nucleotide sugar precursors and incorporate them into chondroitin sulfate proteoglycan (CSPG), allowing specific labeling at each step in chondroitin sulfate synthesis. Subcellular fractionation following labeling with UDP [14C]xylose, UDP-[14C]galactose, UDP-[14C]glucuronic acid, or [35S]PAPS localized the labeled CSPG to the compartment where each glycosylation reaction occurred. From these experiments it appears that xylose addition begins in the endoplasmic reticulum and continues in the Golgi apparatus where galactose, glucuronic acid, and sulfate are added. This conclusion was confirmed by direct visualization of xylose incorporation using electron microscopic autoradiography (Vertel, B. M., Walters, L. M., Flay, N., Kearns, A. E., and Schwartz, N. B. (1993) J. Biol. Chem. 268, 11105-11112). Further examination of xylose addition showed that permeable chondrocytes can utilize both exogenous UDP-xylose transported into the lumen and UDP-xylose generated from UDP-glucuronic acid within the lumen. The enzyme responsible for this reaction, UDP-glucuronate carboxy-lyase, co-localized with xylosyltransferase activity in subcellular fractions. Orientation toward the lumen in subcellular compartments was determined by trypsin sensitivity in the permeable chondrocytes. Therefore, we conclude that UDP-xylose can be produced in the lumen of the compartment where it is utilized in CSPG synthesis, obviating the need for a direct transport mechanism for this nucleotide sugar and providing close regulation of UDP-xylose and UDP-glucuronic acid levels. PMID- 8496173 TI - Xylosylation is an endoplasmic reticulum to Golgi event. AB - The subcellular site of xylosylation, the first carbohydrate modification of the core protein that initiates glycosaminoglycan chain synthesis, was characterized in situ. Methods were developed to combine electron microscopic (EM) autoradiography and the radiolabeling of semi-intact chondrocytes. In the accompanying paper, Kearns et al. (Kearns, A. E., Vertel, B. M., and Schwartz, N. B. (1993) J. Biol. Chem. 268, 11097-11104) presented biochemical and subcellular fractionation studies that utilized semi-intact chondrocytes and radiolabeled UDP sugars to overcome obstacles to the direct analysis of xylosylation. The results suggested that xylosylation begins in the endoplasmic reticulum (ER) and continues in the Golgi. The site of xylosylation was not specified further due to the limitations of subcellular fractionation techniques. The studies described in this report were undertaken to localize these modifications directly in situ. Semi-intact cell preparations were optimized for ultrastructural preservation by modifications of permeabilization methods utilizing nitrocellulose filter overlays. Biochemical analysis demonstrated the exclusive incorporation of UDP xylose into the cartilage chondroitin sulfate proteoglycan (aggrecan) core protein and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) into the highly modified proteoglycan monomer. Immunolocalization studies showed the equivalence of cytoplasmic subcompartments in normal and semi-intact chondrocytes at the levels of light and electron microscopy. Once the biochemical and morphological equivalence of intact and semi-intact cells was established, EM autoradiographic studies were pursued using UDP-[3H]xylose and [35S]PAPS. Based on both qualitative and quantitative data, silver grains resulting from incorporated sulfate were concentrated in the perinuclear Golgi, while those resulting from incorporated xylose were found at the cis or forming face of the Golgi and in vesicular regions of the peripheral cytoplasm associated with the late ER. These data support the view that xylose addition begins in a late ER compartment and continues in intermediate compartments, perhaps including the cis-Golgi. PMID- 8496175 TI - Preparation and characterization of a set of deoxyoligonucleotide 49-mers containing site-specific cis-syn, trans-syn-I, (6-4), and Dewar photoproducts of thymidylyl(3'-->5')-thymidine. AB - Deoxyoligonucleotide 49-mers containing a central cis-syn, trans-syn-I, (6-4), or Dewar photoproduct of TpT were constructed for use in repair and replication studies by ligation of shorter photoproduct-containing oligonucleotides. A (6-4) product-containing 6-mer was prepared in 3.4% yield by 254 nm irradiation of d(AATTAA) and converted in nearly quantitative yield to the Dewar isomer by irradiation with Pyrex- and Mylar-filtered medium-pressure mercury arc light. d(CGAATTAAGC) containing a site-specific cis-syn or trans-syn-I dimer was prepared via automated solid-phase DNA synthesis utilizing photoproduct building blocks. The photoproduct-containing 49-mers were characterized by their susceptibility to base cleavage and a number of enzymes routinely used to map the sites of DNA photoproduct formation. 1 M piperidine at 90 degrees C cleaved the Dewar product faster than the (6-4) product, but did not cleave the cyclobutane dimers. The 3'-->5' exonuclease activity of T4 DNA polymerase was completely blocked by all the lesions except the (6-4) product, which it slowly bypassed. T4 endonuclease V did not cleave the (6-4) or Dewar photoproduct, but unexpectedly cleaved the trans-syn-I dimer at most 1% the rate of the cis-syn dimer in double stranded DNA. The trans-syn-I dimer was cleaved at a 50-fold higher rate in double- than in single-stranded DNA. Escherichia coli photolyase was found to be specific for the cis-syn dimer at low concentrations. Implications of this work to methodology for mapping and quantifying DNA photoproducts are also discussed. PMID- 8496174 TI - Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). AB - Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) and hepatocyte nuclear factor-4 (HNF-4) are orphan members of the steroid/thyroid receptor superfamily and exhibit ubiquitous and liver-enriched tissue distribution, respectively. The gene for rat ornithine transcarbamylase (OTC), an ornithine cycle enzyme, is mainly expressed in the liver and is under the control of the promoter and the 11-kilobase upstream enhancer, both of which are liver selective. Two sites of the promoter region and two sites of the enhancer region of the OTC gene, as well as the ovalbumin promoter site, were recognized by both HNF-4 and COUP-TF, showing that these two factors have closely related binding specificities. Since HNF-4 activated expression from the OTC promoter in cotransfection analysis, this factor appears to participate in liver-selective activation of the OTC gene. On the other hand, COUP-TF repressed the expression from the OTC promoter, whereas it activated expression from several other promoters. Therefore, COUP-TF plays a dual regulatory role depending on the promoter context. Repression of a tissue-specific promoter by a ubiquitous transactivator and derepression by a related tissue-enriched transactivator is potentially an important mechanism for tissue-specific activation of a gene. PMID- 8496176 TI - Cis-active elements controlling lung cell-specific expression of human pulmonary surfactant protein B gene. AB - Human surfactant protein B (SPB) is a 79-amino-acid hydrophobic protein that enhances the surface active properties of pulmonary surfactant. SPB is expressed in nonciliated bronchiolar and alveolar type II cells of the respiratory epithelium, and its expression increases markedly late in gestation. In the present study, a human pulmonary adenocarcinoma cell line, H441, was used in both functional and biochemical assays to identify DNA sequences controlling lung cell specific expression of the SPB gene. DNase I hypersensitive studies demonstrated two distinct regions of lung cell-specific hypersensitivity located proximal to the SPB promoter and within the eighth intron of the gene. To functionally define these DNA sequences, a series of plasmid vectors were constructed in which segments of the human SPB gene and 5'-flanking sequence were linked to a CAT reporter gene and assayed for expression in lung and nonlung cell lines. Whereas far upstream and intronic sequences did not contain enhancer-like elements, a 259 base pair DNA segment (base pair -218 to +41) was sufficient to support lung cell specific expression. DNase I footprinting demonstrated that this pulmonary epithelial cell-specific promoter fragment contained five nuclear protein-binding sites, two of which bound lung cell-specific nuclear protein complexes. These results suggest that the pulmonary epithelial cell-specific expression of SPB is determined, in part, by both ubiquitous and cell type-specific protein-DNA interactions within the proximal promoter region. PMID- 8496177 TI - A novel RNA polymerase III transcription factor fraction that is not required for template commitment. AB - We have identified and partially characterized a novel class III transcription factor fraction (TFIIIE) from yeast nuclear extracts. TFIIIE is functionally distinct from the standard yeast transcription factor fractions, TFIIIB and TFIIIC. It is also different from either of the TFIIIB subfractions, B' and B". TFIIIE is essential for specific transcription of both tRNA and 5 S RNA genes, its activity is sensitive to proteinase K, and it exhibits an apparent sedimentation coefficient of 4.0 S when analyzed on glycerol gradients. In the case of a tRNA gene, TFIIIE does not play a role in the formation of stable preinitiation complexes containing TFIIIB and TFIIIC. It is required for single as well as multiple rounds of transcription, however. Thus, TFIIIE is involved in the utilization of stable transcription complexes, but its action is not restricted to reinitiation events. PMID- 8496178 TI - A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing. AB - The polypyrimidine (py) tract of introns is required for efficient spliceosome assembly and splicing of pre-mRNAs. A detailed mutational analysis of the py tract of an adenovirus 2 intron was carried out. Utilizing a "precursor in pieces" vector system, it was possible to synthesize py tract mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs were analyzed for in vitro splicing, for formation of splicing complexes, and for binding to proteins in the HeLa nuclear extract. Chimeric pre-mRNAs that contained the yeast branch point consensus sequence (UAC-UAAC) and altered py tracts were also analyzed. Mutational analysis showed the following. First, any mutation in the py tract that affected splicing did so by interferring with complex A formation in spliceosome assembly. Second, introduction of purines into the py tract is detrimental only if the length of the tract is shortened and if there is a reduction in the number of consecutive uracil residues. Third, uracil and cytosine do not have equivalent functions in the py tract. Our results with chimeric pre-mRNAs also show that a strong py tract can partially replace a weak branch point sequence and a strong branch point sequence can partially replace a weak py tract. Finally, the one surprising finding obtained when examining protein binding was that a mutant pre-mRNA did not bind to heterogeneous nuclear ribonucleoprotein C proteins and yet spliced close to wild type level. PMID- 8496179 TI - 5 beta-hydroxylation by the liver. Identification of 3,5,7-trihydroxy nor-bile acids as new major biotransformation products of 3,7-dihydroxy nor-bile acids in rodents. AB - 24-Norursodeoxycholic acid (nor-UDCA), when administered into the anesthetized biliary fistula hamster or injected into the perfusate of an isolated liver, was hydroxylated at C-5 to give 5 beta-hydroxynorursodeoxycholic acid 2 (3 alpha,5,7 beta-trihydroxy-24-nor-5 beta-cholan-23-oic acid), which was secreted into bile mainly as such. Similarly, 24-norchenodeoxycholic acid (nor-CDCA) was 5 beta hydroxylated to give 5 beta-hydroxynor-chenodeoxycholic acid 4 (3 alpha,5,7 alpha trihydroxy-24-nor-5 beta-cholan-23-oic acid), which was also secreted into bile without appreciable further biotransformation. The site of hydroxylation was assigned by 13C and 1H NMR and mass spectrometry. 5-Hydroxylation was a major biotransformation pathway at physiological bile acid loads. 5-Hydroxylation of UDCA also occurred in the perfused rat liver but to a lesser extent. 5 Hydroxylation of nor-UDCA was not observed in rabbit, dog, or man, indicating that its formation is species-specific. 5-Hydroxylation of nor-CDCA and nor-UDCA is the first reported example of hydroxylation of a tertiary carbon atom of bile acids. Nor-dihydroxy bile acids appear to be useful for the detection of minor hydroxylation pathways, because their prolonged hepatobiliary retention exposes them repeatedly to hydroxylases present in the hepatobiliary system. PMID- 8496180 TI - Insulin stimulates serine and tyrosine phosphorylation in the juxtamembrane region of the insulin receptor. AB - Insulin-stimulated autophosphorylation of the cytoplasmic juxtamembrane region of the human insulin receptor was examined by Tricine/SDS-PAGE. Various mutant receptor molecules were used to identify two tryptic phosphopeptides associated with the juxtamembrane region which accounts for 15% of the autophosphorylation of partially purified insulin receptor. These phosphopeptides were immunoprecipitated with an antipeptide antibody against the juxtamembrane sequence and were phosphorylated exclusively on tyrosine. Substitution of both Tyr960 and Tyr953 with alanine eliminated insulin-stimulated phosphorylation of the juxtamembrane region without affecting tyrosine autophosphorylation in the C terminus or regulatory regions. Monosubstitution of Tyr960 with phenylalanine or alanine reduced phosphorylation in the juxtamembrane region by more than 50%, and manual Edman degradation indicated that Tyr960 was phosphorylated in wild-type receptor. In vivo, phosphorylation of the juxtamembrane region accounts for one third of the insulin receptor phosphorylation and contains both phosphoserine and phosphotyrosine. Deletion of Tyr960 and 11 adjacent amino acids eliminated insulin-stimulated phosphorylation of the juxtamembrane region. Substitution of Tyr960 reduced this phosphorylation by more than 50%. The insulin receptor also undergoes serine phosphorylation outside of the juxtamembrane region which depends on the presence of Tyr1151. Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor. PMID- 8496181 TI - Fate of DNA targeted to the liver by asialoglycoprotein receptor-mediated endocytosis in vivo. Prolonged persistence in cytoplasmic vesicles after partial hepatectomy. AB - After intravenous injection, DNA complexed with asialoglycoprotein-polylysine conjugates is endocytosed by hepatocytes via asialoglycoprotein receptors and is expressed transiently. Long term persistence and expression occurs when partial hepatectomy is performed after gene delivery. To determine the intracellular location of the persisting DNA, we transferred a plasmid expressing bacterial chloramphenicol acetyltransferase into the liver of rats in vivo by asialoglycoprotein receptor-mediated endocytosis. The internalized DNA was measured by Southern blot. Twenty min after administration, 80-85% of the plasmid appeared in the liver, 80% of which was within hepatocytes (12,000-18,000 copies/hepatocyte). In sham-operated control rats, the transgene concentration decreased to 8-12 and 2-4% of the initial levels in 4 and 24 h, respectively, and became undetectable at 7 days. In rats subjected to 66% hepatectomy 20 min after DNA administration, 20, 9, and 7% of the plasmid in the residual liver persisted at 4 h, 24 h, and 7 days, respectively. Liver homogenates were fractionated by differential centrifugation and Percoll gradient centrifugation. In 66% hepatectomized rats, the plasmid persisted in an undegraded, transfection competent form in plasma membrane/endosome-enriched fractions throughout the duration of the experiment (7 days), indicating that cytoplasmic vesicles are the main site of persistence of the endocytosed DNA. PMID- 8496182 TI - Symmetrical disulfide bonds are not necessary for assembly and secretion of human fibrinogen. AB - Human fibrinogen is a dimer, and each half-molecule is composed of three different polypeptides (A alpha, B beta, and gamma). The two half-molecules are joined together at the amino-terminal ends by three symmetrical disulfide bonds between adjacent A alpha chains, at position 28, and between adjacent gamma chains at gamma 8 and 9. To determine the role of these disulfide bonds in fibrinogen assembly and secretion, site-directed mutagenesis was used to change cysteines of A alpha 28 and gamma 8 and 9 to serine, the mutant chains were coexpressed with normal fibrinogen chains in COS cells, and assembly and secretion of fibrinogen were measured. Elimination of the symmetrical disulfide bonds did not affect assembly of the chains and dimeric fibrinogen was secreted. Analysis by plasmin digestion indicated that the secreted mutant fibrinogens have a similar structure to normal fibrinogen. Our results indicate that other domains of fibrinogen participate in dimer formation and that the three symmetrical disulfide bonds are not crucial for assembly and secretion of fibrinogen. PMID- 8496183 TI - The apical Cl/HCO3 exchanger of beta intercalated cells. AB - There are two types of intercalated cells of the renal collecting duct; one secretes H+ and the other secretes HCO3-. The H(+)-secreting form has an apical vacuolar H(+)-ATPase and a basolateral Cl/HCO3 exchanger that cross-reacts with antibodies to band 3, the product of the AE1 gene. The HCO3(-)-secreting form has a basolateral vacuolar H(+)-ATPase and an apical Cl/HCO3 exchanger, whose identity has not been established previously. Apical membrane vesicles of beta intercalated cells purified from rabbit kidney cortex contain both an electroneutral Cl/HCO3 exchange activity and polypeptides that react with antibodies to band 3 on Western blots. Furthermore, both primary cultures of HCO3(-)-secreting intercalated cells and an immortalized cell line derived from these cells express AE1 and have an apical Cl/HCO3 exchanger. Apical membranes purified from these cells contain a 100-kDa polypeptide that cross-reacts with antibody to the cytoplasmic domain of band 3. These data suggest that the apical Cl/HCO3 exchanger of HCO3(-)-secreting intercalated cells is band 3. PMID- 8496184 TI - Cloning and characterization of a putative Ca2+/H+ antiporter gene from Escherichia coli upon functional complementation of Na+/H+ antiporter-deficient strains by the overexpressed gene. AB - DNA libraries from alkaliphilic Bacillus firmus OF4 had been screened earlier (Ivey, D.M., Guffanti, A.A., Bossewitch, J. S., Padan, E., and Krulwich, T. A. (1991) J. Biol. Chem. 266, 23483-23489) for clones that would functionally complement a strain of Escherichia coli (NM81) with a deletion in one of its Na+/H+ antiporter genes. During those studies, an alkaliphile antiporter gene was hypothesized to have been incorporated into the chromosome of strain NM81, producing Na(+)-resistant NM8191. After introduction of a deletion in the second known E. coli Na+/H+ antiporter gene, libraries were prepared from NM8191 and screened for complementation of Na+/H+ antiporter-deficient mutants of E. coli. Instead of retrieving an alkaliphile gene, an unexpected E. coli gene was identified on the basis of its ability to restore Na+ resistance and membrane Na+/H+ antiporter activity to such mutant strains. The active open reading frame in the clone maps at 27 min on the E. coli chromosome and is identical in sequence to a wild type counterpart. It would be predicted to encode an extremely hydrophobic protein with multiple membrane-spanning regions and a molecular weight of 39,200. A region in one of the predicted hydrophilic loops in the gene product structure possesses striking sequence similarity to calsequestrin. The Ca2+/H+ antiporter activity of membranes from an E. coli transformant with a clone possessing only this open reading frame was indeed found to have enhanced pH-independent Ca2+/H+ antiporter activity. The Ca2+/H+ and Na+/H+ antiporter activities conferred by the clone were both inhibited by Mg2+. The gene was designated chaA and is proposed to be the structural gene for a Ca2+/H+ antiporter whose overexpression leads to resistance to growth inhibition by both calcium and sodium. PMID- 8496185 TI - Molecular analysis of the essential gene for adenylate kinase from the fission yeast Schizosaccharomyces pombe. AB - The enzyme-catalyzed transfer of the terminal phosphoryl group from ATP to an acceptor molecule is an important reaction in a wide variety of biological processes. I demonstrate here the essential function of an ATP:AMP phosphotransferase (adenylate kinase) in the fission yeast Schizosaccharomyces pombe. A cDNA clone encoding immunoreactive adenylate kinase from S. pombe was isolated from a lambda gt11 expression library by cross-reaction with antibodies raised against the recently characterized ADK1 enzyme from the budding yeast Saccharomyces cerevisiae. Subsequent cloning and nucleotide sequence analysis of the S. pombe adenylate kinase gene, adk1, revealed a coding region of 660 nucleotides. The alignment of the two amino acid sequences from S. cerevisiae and S. pombe shows 67% identity. By gene disruption and tetrad analysis it is demonstrated that adk1 is absolutely essential for cell viability. This is in contrast to the ADK1 gene of S. cerevisiae, the deletion of which was shown to lead to a slower cell growth rate rather than to a lethal phenotype. Expression of adk1 in the S. cerevisiae ADK1 deletion strain restored normal cell growth, demonstrating that ADK1 and adk1 are functionally interchangeable. However, despite lack of absolute substrate specificity of adenylate kinases, adk1 could not complement the loss of function of the guanylate kinase encoding gene in a S. cerevisiae null mutant strain, thus highlighting the functional uniqueness of each nucleoside monophosphate kinase. Using suitable expression vectors, large amounts of active adk1 enzyme were produced in either yeast species and in E. coli. The purified enzyme exhibits a high preference for adenine nucleotides, with ATP being a 10 times more efficient phosphoryl donor than GTP. PMID- 8496186 TI - Three-dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand. AB - Many proteins exhibit a large-scale movement of rigid globular domains. Among these, bacterial periplasmic binding proteins involved in substrate transport, or transport and chemotaxis, can be used as prototypes for understanding the mechanism of the movement. Such movements have been found to be associated with specific functions, such as substrate binding, catalysis, and recognition by other biomolecules. We have determined the three-dimensional structures of the lysine/arginine/ornithine-binding protein (LAO) from Salmonella typhimurium with and without lysine by x-ray crystallographic methods at 1.8- and 1.9-A resolution, respectively. The structures are composed of two lobes held together by two short connecting strands. The two lobes are far apart in the unliganded structure, but in contact with each other in the lysine-liganded structure. The large movement of the lobes is a consequence of a 52 degrees rotation of a single backbone torsion angle in the first connecting strand and of distributed smaller changes of three backbone torsion angles of the second connecting strand. The absence of contact between the lysine and the connecting strands suggests that the ligand does not induce the conformational change directly. We instead propose that the unliganded protein undergoes a dynamic change between an "open" and a "closed" conformation and that the role of the ligand is to stabilize the closed conformation. We discuss the nature of a surface area which might be recognized by the membrane-bound complex of these amino acids transport systems. PMID- 8496187 TI - Mapping regions of yeast transcription factor IIIA required for DNA binding, interaction with transcription factor IIIC, and transcription activity. AB - TFIIIA, a site-specific DNA-binding protein containing nine zinc finger motifs, is an RNA polymerase III transcription factor responsible for the assembly of a transcription complex on the 5 S RNA gene. We have analyzed the effect of deleting various regions of yeast TFIIIA on its ability to bind to the internal control region of the yeast 5 S RNA gene, to recruit TFIIIC into the TFIIIA.DNA complex and to promote in vitro transcription of the 5 S RNA gene. A truncated polypeptide containing only the three amino-terminal zinc fingers retained the ability to bind specifically to the internal control region of the 5 S RNA gene. The TFIIIA.DNA complex formed with this three zinc finger module was able to recruit TFIIIC but could not promote transcription. An 81-amino acid domain, which interrupts the repeating zinc finger motifs between fingers 8 and 9, was found to be essential for the transcription activity of the protein. Removal of the carboxyl-terminal region of yeast TFIIIA that extends beyond the ninth zinc finger motif had no effect on the in vitro activities of the protein. Extending the carboxyl-terminal deletion to include the ninth zinc finger led to reduced transcription activity. We speculate that the ninth zinc finger serves to anchor the carboxyl-terminal portion of TFIIIA on the 5 S RNA gene, correctly orienting the 81-amino acid domain to serve its role in promoting transcription. Removal of the region of the protein amino-terminal to the first zinc finger motif was without effect. Extending the amino-terminal deletion to include the first zinc finger appeared to decrease the affinity of TFIIIA for DNA without affecting the specificity of the protein-DNA interaction. The resultant TFIIIA.DNA complex was defective in recruiting TFIIIC and did not support transcription. PMID- 8496188 TI - Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. AB - We have investigated an oxidoreductive regulatory pathway for the DNA binding activity of a pleiotropic cellular transcription factor, nuclear factor kappa B (NF kappa B), has been investigated by using NF kappa B prepared from the nucleus and the cytosol of the primary human T lymphocytes. We show that a cellular reducing catalyst thioredoxin (Trx) plays a major role in activation of the DNA binding of NF kappa B in vitro and stimulation of transcription from the NF kappa B-dependent gene expression. We demonstrate evidence suggesting that redox regulation of NF kappa B by Trx might be exerted at a step after dissociation of the inhibitory molecule I kappa B, a cytosolic-anchoring protein for NF kappa B. To examine the effect of Trx in intact cells, we performed transient assay with a chloramphenicol acetyltransferase-expressing plasmid under the control of human immunodeficiency virus (HIV) long terminal repeat and an effector plasmid expressing human Trx. The promoter activity from HIV long terminal repeat was greatly augmented by co-transfecting the Trx-expressing plasmid, whose effect was dependent on the NF kappa B-binding sites. These findings have suggested that cysteine residue(s) of NF kappa B might be involved in the DNA-recognition by NF kappa B and that the redox control mechanism mediated by Trx might have a regulatory role in the NF kappa B-mediated gene expression. These results may also provide a clue to understanding of the molecular process of AIDS pathogenesis and its possible biochemical intervention. PMID- 8496189 TI - High mobility group proteins 14 and 17 can space nucleosomes in vitro. AB - Recently we partially purified from Xenopus laevis ovaries a novel, ATP dependent, spacing activity that can convert a DNA template consisting of irregularly spaced nucleosomes into a chromatin structure made up of regularly spaced nucleosomes with a repeat length of 160-165 base pairs. In a second independent step, the longer spacing of higher eukaryotic chromatin can be generated by the addition of histone H1. The partially purified spacing fraction contains several proteins that display chromatographic properties and mobilities on polyacrylamide gels similar to high mobility group (HMG) proteins. For that reason, different HMG proteins were tested for their ability to generate chromatin structures with regularly spaced nucleosomes. In this report, using two different nucleosome assembly systems, we show that the addition of phosphorylated HMGs 14 and 17 to the histone octamer results in the formation of chromatin with a repeat length of 160-165 base pairs. The results are similar to those obtained from studies of chromatin structure in simple cells, such as fungi and yeast, and in active genes. PMID- 8496190 TI - Inside-out integrin signaling in macrophages. Analysis of the role of the alpha 6A beta 1 and alpha 6B beta 1 integrin variants in laminin adhesion by cDNA expression in an alpha 6 integrin-deficient macrophage cell line. AB - Leukocytes use the alpha 6 beta 1 integrin to adhere to laminin based on mAb inhibition and affinity chromatography studies. This adhesion requires leukocyte stimulation with either PMA or specific cytokines, a process that has been termed "inside-out" integrin signaling. In the present study, the involvement of alpha 6 integrin structural variants in this regulated adhesion was examined using mouse macrophages. The two known alpha 6 structural variants, alpha 6A and alpha 6B, differ only in their cytoplasmic domain sequences. Using reverse transcriptase polymerase chain reaction, we observed that macrophages express only the alpha 6A structural variant, in contrast to most cell types which express both alpha 6A and alpha 6B variants. The role of this integrin subunit in macrophage adhesion was assessed by cDNA transfection of P388D1 cells. We found that this mouse macrophage cell line does not adhere to laminin even in response to phorbol 12 myristate 13-acetate (PMA) stimulation, though it does adhere normally to fibronectin and tissue culture plastic. Subsequent analysis employing reverse transcriptase-polymerase chain reaction and immunoprecipitation of surface labeled cells revealed that this cell line expresses neither the alpha 6A nor alpha 6B integrin subunits. Stable transfection of either the chick or human alpha 6A cDNAs into P388D1 cells resulted in chimeric alpha 6A beta 1 surface expression. The alpha 6A transfectants exhibited inside-out integrin signaling because PMA stimulation markedly increased their ability to adhere to laminin but it did not increase alpha 6A beta 1 surface expression. Similar results were obtained after transfection of the human alpha 6B cDNA. Analysis of the human transfectants was facilitated by the generation of a monoclonal antibody, 2B7, that is specific for the human alpha 6 integrin subunit. These observations demonstrate that both alpha 6A beta 1 and alpha 6B beta 1 can be regulated by inside-out signaling pathways in macrophages, even though this cell type expresses only alpha 6A beta 1. The data presented also demonstrate clearly that the alpha 6A and alpha 6B cytoplasmic domains do not differ in their ability to be regulated by PMA. PMID- 8496191 TI - Regulatory sequences on the human villin gene trigger the expression of a reporter gene in a differentiating HT29 intestinal cell line. AB - To develop a molecular tool for tissue-specific targeting of gene expression in immature and differentiated epithelial cells of the small and large intestinal mucosa, we have isolated the 2-kb 5'-flanking region of the human villin gene. This region contains numerous short sequences that are conserved among other tissue-specific promoters of genes expressed in differentiated enterocytes. This DNA fragment promotes the transcription and expression of the luciferase reporter gene in villin-positive intestinal, renal, and hepatoma cell lines but not in a villin-negative keratinocyte cell line. The pattern of expression corresponds that of the endogenous gene, indicating that this sequence can direct intestine specific transcription. In the differentiating HT29 intestinal cell line, expression of the reporter gene is already detectable in undifferentiated cells, and dramatically increases when terminal differentiation is induced. Thus, as previously reported for the endogenous gene the isolated 5'-flanking region of the villin gene responds positively to conditions known to stimulate terminal differentiation of these cultured epithelial intestinal cells. The reported results indicate that this genomic fragment contains sufficient regulatory elements to recapitulate the expression pattern of the villin promoter during intestinal differentiation. PMID- 8496192 TI - Organization and promoter activity of the mouse syndecan-1 gene. AB - Syndecan-1, the prototype of a family of heparan sulfate-containing integral membrane proteoglycans, associates extracellularly with a variety of matrix molecules and growth factors and intracellularly with the actin cytoskeleton. Expressed constitutively on epithelia in mature tissues and in a developmentally regulated manner on epithelial and induced mesenchymal cells during embryogenesis, syndecan-1 appears to be involved in controlling the shape and organization of cells and tissues. To better understand the function and regulation of syndecan-1, we determined the structure of the mouse syndecan-1 gene (Synd-1). Synd-1 is approximately 19.5 kilobases in size and is organized into five exons that appear conserved in other family members. Exon 1 encodes the signal peptide; exon 2, the N-terminal glycosaminoglycan attachment region; exon 3, the bulk of the extracellular domain; exon 4, the protease-susceptible site; and exon 5, the transmembrane and cytoplasmic domains which are highly homologous between syndecan family members. Synd-1 has three transcriptional start sites, two polyadenylation sites, and is not alternatively spliced to produce its 2.6- and 3.4-kilobase mRNA species. Upstream sequences have promoter activity and contain TATA and CAAT boxes as well as a variety of other potential binding sites for transcription factors, including Sp1 (GC box), NF-kappa B, MyoD (E box), and Antennapedia. The structure of the promoter region suggests that control of Synd 1 expression is both constitutive and developmentally regulated. Because Synd-1 exons encode discrete functional domains of the syndecan-1 protein that are conserved throughout the syndecan family, all syndecan genes are likely derived from a common ancestor. PMID- 8496193 TI - Mouse procathepsin L lacking a functional glycosylation site is properly folded, stable, and secreted by NIH 3T3 cells. AB - The role of glycosylation in the synthesis, transport, and localization of procathepsin L has been analyzed. Procathepsin L is the precursor form of a lysosomal cysteine protease which is synthesized in large amounts by malignantly transformed cells and cells treated with growth factors or tumor promoters. As for other lysosomal hydrolases, procathepsin L is predominantly secreted when it is overexpressed, despite the presence of the lysosomal sorting marker mannose 6 phosphate. To study the role of glycosylation in procathepsin L trafficking, we constructed a cDNA in which the codon for Asn-204 was mutated to encode Gln. When this mutated cDNA was transfected into NIH 3T3 cells, a completely nonglycosylated form of procathepsin L was expressed. The protein appeared to be folded properly, as judged by its ability to be proteolytically processed to a lower molecular weight form during incubation at pH 4. Nonglycosylated protein was stable, both as unprocessed proenzyme and after processing at pH 4, and it was predominantly secreted instead of being delivered to lysosomes. Nonglycosylated and endogenous glycosylated procathepsin L were secreted by NIH 3T3 cells with identical kinetics. These studies therefore confirm that Asn-204 is the normal functional carbohydrate acceptor in procathepsin L and that carbohydrate in wild-type procathepsin L serves predominantly as a lysosomal targeting signal, with little or no role in protein folding or stability. Furthermore, there does not appear to be a major mannose 6-phosphate-independent route of lysosomal localization in NIH 3T3 cells. In experiments with a second mutant, the glycosylation signal at Asn-251, which normally is not utilized, was capable of serving as a carbohydrate acceptor, suggesting that there is normally a structural impediment to glycosylation at Asn-251 in procathepsin L. PMID- 8496194 TI - Overexpression in Escherichia coli and affinity purification of chick kidney ferredoxin. PMID- 8496195 TI - Science and surgery. PMID- 8496196 TI - Surgery for brachial plexus injuries. PMID- 8496197 TI - Antibiotic depots. PMID- 8496198 TI - Innovations in surgery. A proposal for phased clinical trials. AB - There is an urgent need for the staged, controlled, introduction of new technology and new procedures to surgery. A classification system in four stages is proposed, which would allow for prospective assessment of new devices or methods before they are released for use by the surgical community. The proposal recognises the unique nature of a surgical operation and its learning curve. The issues of randomisation and of informed consent are discussed, and are shown not to be barriers to clinical trials, but necessary adjuncts to orderly testing. The importance of continued surveillance of innovations is emphasised. PMID- 8496199 TI - Audit of a bone bank. AB - The results are reported of an audit of allografts collected in the first 18 months of the Leicester Bone Bank. We retrieved 161 femoral heads at primary arthroplasty of which 103 were implanted into 59 patients. There were deep infections in two recipients and wound infections in five. In two of these cases, culture of the femoral head at implantation was positive but the organisms grown were not those which caused the clinical infection. We retrieved 22 large allografts from six cadavers. Four of these were contaminated at retrieval and required irradiation for sterilisation. There has been one clinical infection in the nine large allografts implanted so far. We recommend that all bone banks undertake prospective audit to ensure that high standards are maintained and wastage minimised. PMID- 8496200 TI - Methods of assessing new bone formation during limb lengthening. Ultrasonography, dual energy X-ray absorptiometry and radiography compared. AB - We studied the quantity and rate of formation of new bone during lengthening of 17 limb segments in 10 patients using dual-energy X-ray absorptiometry (DEXA), ultrasonography and radiography. Whereas new bone was detected by both DEXA and ultrasonography within 1 to 2 weeks of distraction, it was not visible on the radiographs until 4 to 8 weeks. Limb alignment and gap measurement were accurately assessed by DEXA without the need for standard radiographs or scanograms. With ultrasound the distraction gap appeared as an echolucent window which narrowed progressively producing a hyper-reflecting line after which further consolidation could not be assessed. As measured by DEXA the density of the new bone at this stage was approximately 45% of control values and did not represent normal cortication. Whereas ultrasound could be used to identify defects in mineralisation and to determine when to dynamise the fixator system, DEXA could measure the quantity and rate of formation of bone throughout lengthening. PMID- 8496201 TI - Early detection of avascular necrosis of the femoral head by MRI. AB - We used MRI to examine the hips of 32 asymptomatic patients at 9 to 21 months after renal transplantation covered by high-dose corticosteroids. Five hips in three patients showed changes which indicate avascular necrosis, although radiographs, CT scans and isotope scans were normal. These patients had repeat MRI scans after another two years and three years. One patient with bilateral MRI changes developed symptoms and abnormal radiographs and CT and isotope scans in one hip nine months after the abnormal MRI. Intraosseous pressure was found to be raised in both hips, and core biopsies revealed necrotic bone on both sides. The other three hips have remained asymptomatic with unchanged MRI appearances three years after the initial MRI. It seems that idiopathic avascular necrosis does not always progress to bone collapse in the medium term. PMID- 8496202 TI - White cell scans and infected joint replacements. Failure to detect chronic infection. AB - We report the results of imaging with labelled white cells in 52 patients before the revision of 54 cemented joint prostheses at which the diagnosis of infection was made from biopsies. Twenty-five hips were imaged with 111In-oxine-labelled cells; 20 hips and 11 knees were imaged with 99mTc-hexamethylpropylene-amineoxime labelled cells. Of these, 13 hips and five knees proved to be infected. The scans taken together had an accuracy of 82%, a sensitivity of 44% and a specificity of 100%. Indium scans gave 37% sensitivity, 99mTc labelling 50% sensitivity. Infected arthroplasties with positive scans had presented significantly earlier than those with negative scans, the time after the original insertion being 1.1 years for the true-positive scans and 6.1 years for the false-negative scans. The value of labelled white-cell scans in the detection of infection in failed joint replacements is dependent on the activity of the infection. There is reduced sensitivity to the more insidious infections which affect arthroplasties and aspiration under controlled conditions remains an important investigation. PMID- 8496203 TI - Two-stage management of chronic osteomyelitis of the long bones. The Belfast technique. AB - We treated 37 patients with chronic osteomyelitis of the tibia (25), femur (9), radius (2) and humerus (1) by a two-stage technique, comprising radical debridement of all infected bone and soft tissue with the provision of soft tissue cover, and delayed autogenous bone grafting when necessary. All patients were reviewed at an average of 49 months (12 to 121). Infection-free bone union was achieved in 34. No patient required amputation. Wide excision of all compromised tissue and the closure of bone within a healthy vascularised soft tissue envelope are essential if infection is to be eradicated. The combined assessment and management of such patients by an orthopaedic surgeon and a plastic surgeon are advocated. PMID- 8496204 TI - Symptoms and signs in degeneration of the lumbar spine. A prospective, consecutive study of 300 operated patients. AB - In a prospective, consecutive study we determined the frequency of common symptoms and signs in 300 patients with lumbar nerve-root compression syndromes. We compared 100 patients with disc herniation (mean age 43 years), 100 with lataral spinal stenosis (41 years) and 100 with central spinal stenosis (65 years), using a standard protocol of common signs and symptoms. The diagnoses were established by one or more of myelography, CT, MRI and nerve-root block, and all were confirmed at operation. The preoperative duration of symptoms was significantly shorter in patients with disc herniation. Pain at rest, at night, and on coughing was as common in lateral stenosis as in disc herniation, but regular consumption of analgesics was more common in patients with disc herniation. Positive straight-leg-raising tests were more common in disc herniation than in lateral stenosis and were uncommon in central stenosis. Motor disturbances were seen most often in central spinal stenosis, especially patellar reflex changes. Sensory disturbances were most common in patients with complete disc herniation. PMID- 8496205 TI - The surgical treatment of central lumbar stenosis. Multiple laminotomy compared with total laminectomy. AB - We assigned 67 patients with central lumbar stenosis alternately to either multiple laminotomy or total laminectomy. The protocol, however, allowed multiple laminotomy to be changed to total laminectomy if it was thought that the former procedure might not give adequate neural decompression. There were therefore three treatment groups: group I consisting of 26 patients submitted to multiple laminotomy; group II, 9 patients scheduled for laminotomy but submitted to laminectomy; and group III, 32 patients scheduled for, and submitted to, laminectomy. The mean follow-up was 3.7 years. Bilateral laminotomy at two or three levels required a longer mean operating time than total laminectomy at an equal number of levels. The mean blood loss at surgery and the clinical results did not differ in the three groups. The mean subjective improvement score for low back pain was higher in group I but there was also a higher incidence of neural complications in this group. No patient in group I had postoperative vertebral instability, whereas this occurred in three patients in groups II and III, who had lumbar scoliosis or degenerative spondylolisthesis preoperatively. Multiple laminotomy is recommended for all patients with developmental stenosis and for those with mild to moderate degenerative stenosis or degenerative spondylolisthesis. Total laminectomy is to be preferred for patients with severe degenerative stenosis or marked degenerative spondylolisthesis. PMID- 8496206 TI - Surgery for lumbar spinal stenosis in old people. AB - We have reviewed 31 consecutive patients, aged 65 years or more, after surgical decompression for degenerative lumbar spinal stenosis. The average follow-up was 42 months. Assessment included a standard questionnaire, a pain diagram which was completed by the patient, and clinical and radiological examination. Patients were considered in three groups; degenerative spondylolisthesis (19), lateral recess stenosis (5), and central-mixed stenosis (7). The indication for surgery was leg pain: no patient had an operation for back pain alone. Fusion was never performed. Overall, 64% of the patients had an excellent result, 17% a good result and 19% a poor result. We conclude that the long-term outcome of decompressive surgery in the elderly is good; it does not differ from that reported for younger patients. PMID- 8496207 TI - Repair of spondylolysis in young fast bowlers. AB - Fast bowling in the game of cricket requires repetitive spinal extension, lateral deviation, lumbar flexion and thoracodorsal rotation. Back pain is common, and it has been shown that pars interarticularis defects had occurred in over 50% of a group of teenage fast bowlers. Many of these defects will heal, but some cause chronic pain which prevents bowling, although other activities may be painless. We report the successful results of local screw fusion of the pars interarticularis defects in ten bowlers, and recommend this method for this small group of sportsmen. PMID- 8496208 TI - Neurological complications of the reduction of cervical spine dislocations. AB - We have studied the case records of 16 patients with dislocations of the cervical spine who deteriorated neurologically during or after reduction. The dislocations were reduced by skull traction in four patients, by manipulation in four and by operation in seven. This complication was not related to age, sex, mechanism of injury, or the level and the type of dislocation. Fourteen patients made substantial recoveries, one made a partial recovery and one patient remained totally paralysed and died three months later. The causes and prevention of spinal-cord damage at this stage of management are discussed, and the early use of MRI or CT myelography is recommended. PMID- 8496209 TI - Vertebral artery injury during anterior decompression of the cervical spine. A retrospective review of ten patients. AB - Ten patients who suffered iatrogenic injury to a vertebral artery during anterior cervical decompression were reviewed to assess the mechanisms of injury, their operative management, and the subsequent outcome. All had been undergoing a partial vertebral body resection for spondylitic radiculopathy or myelopathy (4), tumour (2), ossification of the posterior longitudinal ligament (1), nonunion of a fracture (2), or osteomyelitis (1). The use of an air drill had been responsible for most injuries. The final control of haemorrhage had been by tamponade (3), direct exposure and electrocoagulation (1), transosseous suture (2), open suture (1), or open placement of a haemostatic clip (3). Five patients had postoperative neurological deficits, but most of them resolved. We found direct arterial exposure and control to be safe, quick and reliable. Careful use of the air drill, particularly in pathologically weakened bone, as in infection or tumour, is essential. Arterial injury is best avoided by a thorough knowledge of the anatomical relationships of the artery, the spinal canal, and the vertebral body. PMID- 8496210 TI - Arthroscopic debridement versus open repair for rotator cuff tears. A prospective cohort study. AB - We compared two treatments for tears of the rotator cuff of 1 to 4 cm in size. One group of 22 patients had an arthroscopic subacromial decompression and rotator-cuff debridement; the other comparable group of 23 patients had open repair and acromioplasty. Review was at 2 to 5 years postoperatively. Both groups had similar pain relief and range of active forward flexion, with significant improvement from the preoperative condition. The open repair group scored better for function, strength and overall score, but patient satisfaction was similar in the two groups. We recommend the use of arthroscopic subacromial decompression and debridement for low-demand patients who require mainly pain relief and range of movement. Open repair is necessary if strength and functional recovery are the prime objectives. PMID- 8496211 TI - Ultrasonography of pulled elbow. AB - We used ultrasonography in ten children with pulled elbow to compare measurements of the radiocapitellar distance (RCD) on the affected and the unaffected sides. Similar measurements were made in a group of ten age-matched normal children. The mean RCD in pronation of the affected and normal sides in the patients with pulled elbows was 7.2 mm +/- 0.7 and 3.8 mm +/- 0.5, respectively (p < 0.0001). In the normal children the mean RCD in pronation was 4.5 mm +/- 0.5. We conclude that ultrasonography is of value for documenting pulled elbow in children. PMID- 8496212 TI - Nonunion of fractures of the scaphoid tuberosity. AB - Fracture of the tuberosity of the scaphoid is common and usually heals without incident because of the good blood supply. We report four cases of nonunion of this fracture. Three of them were symptomatic and two required operative treatment. PMID- 8496213 TI - Late reduction of dislocated elbow. Need triceps be lengthened? AB - We compared the results in two groups of patients with late reduction of posterior elbow dislocations, one of which had lengthening of the triceps (group A, n = 36) and the other did not (group B, n = 34). The elbows had all been dislocated for more than one month and less than three months. The patients in group B had better clinical results and significantly less postoperative flexion contracture (p < 0.05). PMID- 8496214 TI - Cystic change in the head of the fibula in osteoarthritis. AB - We report eight patients with prominent cystic changes in the head of the fibula. Seven of these had osteoarthritis of the adjacent knee, and five had evidence of local deposition of calcium pyrophosphate dihydrate crystals. A radiographic survey of 470 knees in 254 patients with osteoarthritis suggested that such cysts are rare, but should be considered in the differential diagnosis of such changes before expensive or invasive investigations are performed. PMID- 8496215 TI - Proprioception at the ankle: the effect of anaesthetic blockade of ligament receptors. AB - Seven subjects with normal joints were tested for active and passive position sense of ankle inversion, peroneal reflex reaction time to sudden ankle inversion, and postural stability during single-leg stance. The tests were performed before and after regional block of the ankle and foot with local anaesthetic. Passive position sense, assessed with the muscles relaxed, was greatly impaired by anaesthesia but active position sense, with the calf muscles activated, was preserved, and the peroneal reaction time to sudden ankle inversion was not altered. The magnitude of postural sway during single-leg stance was also unchanged by anaesthesia of the ankle and foot. The results suggest that the afferent input from intact lateral ankle ligaments is important in sensing correct placement of the foot at heel-strike, but that this input can be replaced by afferent information from active calf muscles. Afferent input from these muscles seems also to be responsible for dynamic ankle protection against sudden ankle inversion and is adequate to allow stable single-leg stance. PMID- 8496216 TI - Anterior impingement of the ankle treated by arthroscopic removal of bony spurs. AB - We reviewed 17 patients after arthroscopic resection for anterior impingement in the ankle. All had had painful limitation of dorsiflexion which had failed to respond to conservative treatment. Review at an average of 39 months showed very significant improvements in levels of pain, swelling, stiffness, limping and activity. There was a significant improvement in the range of dorsiflexion but not of plantar flexion. One poor result was due to a superficial infection, and two other patients had residual numbness of the foot which persisted for several months. PMID- 8496217 TI - The incidence of proximal femoral fractures in an English county. AB - We have studied the incidence of fractures of the proximal femur in one English county from 1968 to 1991. Numbers have increased steadily, but the age-specific incidence has remained relatively unchanged since 1981. The increase is due to the rise in the population most at risk; this is likely to continue causing a 20% increase in demand for treatment by the year 2000. Suitable allocation of resources must be planned. PMID- 8496218 TI - Unstable intertrochanteric fracture of the femur. A prospective randomised study comparing anatomical reduction and medial displacement osteotomy. AB - We conducted a prospective randomised trial to compare the results of anatomical reduction and medial displacement osteotomy in 127 consecutive patients with unstable intertrochanteric fractures, of whom 109 completed the study. After an average follow-up of 11 months, we found no significant differences in walking ability, social status or failure of fixation in the two groups. Postoperative complication rates and the early mortality rate were not significantly different, but operating time and blood loss were significantly higher in the osteotomy group. With the use of modern sliding hip screws, medial displacement osteotomy is rarely indicated for unstable intertrochanteric fractures. PMID- 8496219 TI - Unrecognised joint penetration in treatment of femoral neck fractures. AB - Screw devices used to treat fractures of the femoral neck are usually positioned under image-intensifier control, using anteroposterior and lateral views. The volume projected by these views is over 27% larger than the femoral head; the tips of screws so placed may be outside the femoral head. This can be avoided by placement within the central two-thirds of the head: we have designed a template which can confirm safe placement. PMID- 8496220 TI - Algodystrophy and osteoporosis after tibial fractures. AB - We made a prospective study of the incidence and natural history of algodystrophy and associated changes in bone mineral density in the ankles and feet of 60 consecutive patients who had suffered unilateral fractures of the tibial shaft. At bone union, 18 patients showed signs of algodystrophy. Its development was independent of the type of fracture management and of the severity of injury. Patients with algodystrophy lost significantly more bone mineral than did those without but the degree of this loss was independent of the type of treatment and of the time to fracture union. In most cases the symptoms resolved within six months of fracture union but in four patients they were still present at one year and two of these had not returned to work. PMID- 8496221 TI - Redisplacement after manipulation of distal radial fractures in children. AB - We reviewed 68 fractures of the distal radius in children, all treated by primary manipulation and plaster immobilisation. Complete displacement of the fracture and failure to achieve a perfect reduction were both associated with a significant increase in the chance of redisplacement. We recommend the use of percutaneous Kirschner wires to maintain a satisfactory position in all cases in which a perfect reduction cannot be achieved. PMID- 8496222 TI - Rheumatoid nodules at the cement-bone interface in revision arthroplasty of rheumatoid patients. AB - We studied the histology of the cement-bone interface and the regenerated synovium in ten aseptically loosened arthroplasties in rheumatoid patients. In two patients we found rheumatoid nodules at the cement-bone interface and marked lymphoplasmacytic infiltration in another three. Failed joints in osteoarthritic patients did not show these changes, and it seems likely that the presence of abundant immunocompetent cells was due to the background disease. We speculate that rheumatoid inflammation contributed to the process of loosening. PMID- 8496223 TI - Bone surface preparation in cemented joint replacement. AB - We studied the effects of nine techniques of bone surface preparation on cement penetration and shear strength at the cement-bone interface in a standard model of bovine cancellous bone. In unprepared bone the mean penetration was 0.2 mm and the mean shear strength of the interface was 1.9 MPa, less than that of the underlying bone. Brushing with surface irrigation gave mean penetrations of 0.6 to 1.4 mm and mean shear strengths of 1.5 to 9.9 MPa. In 50% of specimens the interface was weaker than the underlying bone. The use of pressurised lavage resulted in mean penetrations of 4.8 to 7.9 mm and mean shear strengths of 26.5 to 36.1 MPa, which were greater than those of the cancellous bone in all specimens. Pressurised lavage was equally effective alone or in combination with brushing, and its efficacy was not altered by using pulsed or continuous jets, or by changing the temperature of the solution from 21 degrees C to 37 degrees C. PMID- 8496224 TI - Flanged acetabular components in cemented Charnley hip arthroplasty. Ten-year follow-up of 350 patients. AB - A flanged socket was introduced by Sir John Charnley for use in his low-friction hip arthroplasty in 1976. Experimental evidence has suggested that the flange offers an advantage in terms of cement pressurisation at the time of implantation. We have reviewed 302 primary Charnley arthroplasties followed for 9 to 11 years to determine the effect of the flanged socket on the radiological appearance. The incidence of radiological demarcation at the cement-bone interface is significantly reduced in early radiographs after the use of a flanged socket, and the advantage is maintained in the long-term results. PMID- 8496225 TI - Total hip reconstruction in acetabular dysplasia. A finite element study. AB - In acetabular dysplasia, fixation of the acetabular component of a cemented total hip prosthesis may be insecure and superolateral bone grafts are often used to augment the acetabular roof. We used finite element analysis to study the mechanical importance of the lateral acetabular roof and found that the lateral acetabular rim plays an important role in the load transfer of the pelvic bone. When the superlateral rim was lacking, the load shifted to the posterosuperior rim and to the area of pubic support, and the stresses in all materials, especially in the cement and in the trabecular bone, increased greatly. At the cement-bone interface the tilting component of the shear stress increased threefold. In a model in which the dysplastic acetabulum was augmented by a rigidly fixed, load-transmitting bone graft, the stresses were considerably diminished. PMID- 8496226 TI - Evaluation of painful hip arthroplasties. Are technetium bone scans necessary? AB - We reviewed the plain radiographs, bone scans and hip aspiration results of 54 patients with painful hip arthroplasties which had been explored surgically, to compare the results of the investigations with the operative findings. For acetabular loosening, the sensitivity and specificity of bone scanning were 87% and 95%, with an accuracy of 90%: for serial plain radiography sensitivity was 95%, specificity 100% and accuracy 97%. For femoral component loosening, bone scan sensitivity was 85%, specificity 100% and accuracy 89%: the sensitivity of plain radiography was 100%, with specificity 92% and accuracy 98%. Technetium bone scanning did not provide additional information with regard to loosening and is not necessary in the routine investigation of a painful hip arthroplasty. Serial pain radiography is the most effective method of detecting loosening, and bone scanning is useful only when radiography is inconclusive with regard to loosening or infection. PMID- 8496227 TI - The reliability of ultrasonographic assessment of neonatal hips. AB - Ultrasound scans were made of the hips of 209 neonates born consecutively over a two-week period. Of the 418 scans, 62 images were selected at random and 25 of these were duplicated to give a total of 87 scans. These static images were then presented to five experienced observers who each made nine different assessments and measurements. Interobserver and intraboserver agreement was calculated and expressed as kappa values. Our results showed poor reliability on both counts. PMID- 8496228 TI - Ultrasound and the Pavlik harness in CDH. AB - Sixty-nine hips in 62 patients were treated by the Pavlik harness for congenital dislocation. Ultrasonography showed three degrees of residual head displacement when the harness was first applied. In type A, the femoral head showed contact with the inner posterior wall of the acetabulum. In type B, it contacted the posterior margin of the socket, with its centre at or anterior to the acetabular rim. In type C, the femoral head was displaced outside the socket, with its centre posterior to the acetabular rim. All 51 hips with type A displacement remained reduced. Of nine hips of type B, five were reduced, but the other four were not. None of the nine hips with type C dislocation became reduced with continued use of the harness. The Pavlik harness is indicated for type A and some type B dislocations, but the latter need daily ultrasound monitoring, with a change in method of treatment if type C displacement appears or if the hip is not reduced within one or two weeks. Treatment by Pavlik harness is not indicated in hips with type C dislocations. PMID- 8496229 TI - Simultaneous multiple operations for spastic diplegia. Outcome and functional assessment of walking in 18 patients. AB - We assessed the outcome after simultaneous multiple operations performed on 18 children with spastic diplegia, with emphasis on the changes in the physiological cost index (PCI) of walking. Fourteen patients had a measurable reduction at one year, but the more severely affected patients took up to two years to reach a new functional plateau. The level of the preoperative PCI allows prediction of the outcome of surgery in terms of reducing the effort of walking, or improving its appearance only. Intrapelvic intramuscular psoas tenotomy produced an improvement of hip flexion deformity in 15 of 17 patients without the loss of muscle power to initiate the swing phase. Fractional lengthening corrected hamstring tightness in 17 cases, and the mean popliteal angle was reduced from 63 degrees preoperatively to 30.2 degrees, with almost complete resolution of the fixed knee flexion deformity present in ten patients. Distal transfer of the rectus femoris, when it was shown to be contracting inappropriately, improved the knee flexion arc during walking from a mean of 28.3 degrees to 45.2 degrees. PMID- 8496230 TI - The management of tibial torsion in patients with spina bifida. AB - We reviewed 20 patients with spina bifida who had had surgical management of tibial torsion. Eight had had bilateral procedures and 12 a unilateral procedure, giving a total of 28 limbs for analysis. We performed closed osteoclasis on seven limbs and tibial osteotomy on 21. In the closed osteoclasis group six limbs (85%) had a good result after an average follow-up of nine years (2 to 22). All limbs developed postoperative anteromedial bowing of the tibia which later remodelled. In the tibial osteotomy group 19 (90%) had a good result. The average follow-up was nine years (2 to 28). Complications occurred in seven limbs (33%). We recommend closed osteoclasis of the tibia for the young patient with spina bifida in whom walking is impeded by excessive internal tibial torsion, and supramalleolar tibial osteotomy in the older patient with excessive external tibial torsion and a planovalgus foot. PMID- 8496231 TI - Split tibialis posterior transfer for equinovarus deformity in cerebral palsy. Long-term results of a new surgical procedure. AB - We report the results of a new surgical procedure for spastic equinovarus deformity due to cerebral palsy. This is the transfer of the anterior half of the split tibialis posterior to the dorsum of the foot through the interosseous membrane. We performed the operation on 23 feet in 18 children. All patients were assessed before operation and at follow-up at a mean of 8.4 years postoperatively. Using the criteria of Kling et al (1985), excellent results were obtained in 14 feet, good results in eight, and a poor result in only one. PMID- 8496232 TI - Computer-assisted and visual measurement of lucent zones. PMID- 8496233 TI - Infection and interposition between ultraclean air source and wound. PMID- 8496234 TI - A mobility progress chart. PMID- 8496235 TI - Anaphylaxis after intra-articular injection of bupivacaine and methylprednisolone. PMID- 8496236 TI - Nitrogen freezing of muscle grafts. PMID- 8496237 TI - Thrombosis and embolism after knee arthroplasty. PMID- 8496238 TI - Measuring spinal radiographs. PMID- 8496239 TI - Patellar fracture after graft removal. PMID- 8496240 TI - Fractures of clavicle and scapular neck. PMID- 8496241 TI - Effects of electromagnetic field exposure on gene transcription. AB - Exposure of whole animals, isolated tissues, and cells to electromagnetic fields of various characteristics has resulted in a substantial literature detailing a wide range of effects at the morphological, physiological, biochemical, and molecular levels. In recent years, considerable effort has been devoted to defining a mechanism by which electromagnetic fields can couple to biological systems and generate this plethora of effects. As a consequence, there has been a growing interest in electromagnetic field-induced alterations in gene expression. Key studies are discussed which indicate that exposure of several cell types to electromagnetic fields that differ in waveform, amplitude, and frequency induced general changes in gene transcription. Moreover, exposure of T-lymphoblastoid cells to a 60 Hz sinusoidal magnetic field altered the transcription of genes encoding c-fos, c-jun, c-myc, and protein kinase C. Future studies in this area should focus on independent replication of key studies and identification of which events in the signal transduction pathways leading to gene transcription are altered by electromagnetic field exposure. PMID- 8496242 TI - Beneficial effects of electromagnetic fields. AB - Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy. PMID- 8496243 TI - Prospects on clinical applications of electrical stimulation for nerve regeneration. AB - Regenerative capability is limited in higher vertebrates but present in organ systems such as skin, liver, bone, and to some extent, the nervous system. Peripheral nerves in particular have a relatively high potential for regeneration following injury. However, delay in regrowth or growth, blockage, or misdirection at the injury site, and growth to inappropriate end organs may compromise successful regeneration, leading to poor clinical results. Recent studies indicate that low-intensity electrical stimulation is equivalent to various growth factors, offering avenues to improve these outcomes. We present a review of studies using electric and electromagnetic fields that provide evidence for the enhancement of regeneration following nerve injury. Electric and electromagnetic fields (EMFs) have been used to heal fracture non-unions. This technology emerged as a consequence of basic studies [Yasuda, 1953; Fukada and Yasuda, 1957] demonstrating the piezoelectric properties of (dry) bone. The principle for using electrical stimulation for bone healing originated from the work of Bassett and Becker [1962], who described asymmetric voltage waveforms from mechanically deformed live bone. These changes were presumed to occur in bone during normal physical activity as a result of mechanical forces, and it was postulated that these forces were linked to modifications in bone structure. Endogenous currents present in normal tissue and those that occur after injury were proposed to modify bone structure [Bassett, 1989]. These investigators proposed that tissue integrity and function could be restored by applying electrical and/or mechanical energy to the area of injury. They successfully applied electrical currents to nonhealing fractures (using surgically implanted electrodes or pulsed currents using surface electrodes) to aid endogenous currents in the healing process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496244 TI - Environmental magnetic fields: influences on early embryogenesis. AB - A 10-mG, 50 to 60-Hz magnetic field is in the intensity and frequency range that people worldwide are often exposed to in homes and in the workplace. Studies about the effects of 50- to 100-Hz electromagnetic fields on various species of animal embryos (fish, chick, fly, sea urchin, rat, and mouse) indicate that early stages of embryonic development are responsive to fluctuating magnetic fields. Chick, sea urchin, and mouse embryos are responsive to magnetic field intensities of 10-100 mG. Results from studies on sea urchin embryos indicate that exposure to conditions of rotating 60-Hz magnetic fields, e.g., similar to those in our environment, interferes with cell proliferation at the morula stage in a manner dependent on field intensity. The cleavage stages, prior to the 64-cell stage, were not delayed by this rotating 60-Hz magnetic field suggesting that the ionic surges, DNA replication, and translational events essential for early cleavage stages were not significantly altered. Studies of histone synthesis in early sea urchin embryos indicated that the rotating 60-Hz magnetic field decreased zygotic expression of "early" histone genes at the morula stage and suggests that this decrease in early histone production was limiting to cell proliferation. Whether these comparative observations from animal development studies will be paralleled by results from studies of human embryogenesis, as suggested by some epidemiology studies, has yet to be established. PMID- 8496245 TI - Electroporation: a general phenomenon for manipulating cells and tissues. AB - Electroporation is a fascinating cell membrane phenomenon with several existing biological applications and others likely. Although DNA introduction is the most common use, electroporation of isolated cells has also been used for: (1) introduction of enzymes, antibodies, and other biochemical reagents for intracellular assays; (2) selective biochemical loading of one size cell in the presence of many smaller cells; (3) introduction of virus and other particles; (4) cell killing under nontoxic conditions; and (5) insertion of membrane macromolecules into the cell membrane. More recently, tissue electroporation has begun to be explored, with potential applications including: (1) enhanced cancer tumor chemotherapy, (2) gene therapy, (3) transdermal drug delivery, and (4) noninvasive sampling for biochemical measurement. As presently understood, electroporation is an essentially universal membrane phenomenon that occurs in cell and artificial planar bilayer membranes. For short pulses (microsecond to ms), electroporation occurs if the transmembrane voltage, U(t), reaches 0.5-1.5 V. In the case of isolated cells, the pulse magnitude is 10(3)-10(4) V/cm. These pulses cause reversible electrical breakdown (REB), accompanied by a tremendous increase molecular transport across the membrane. REB results in a rapid membrane discharge, with the elevated U(t) returning to low values within a few microseconds of the pulse. However, membrane recovery can be orders of magnitude slower. An associated cell stress commonly occurs, probably because of chemical influxes and effluxes leading to chemical imbalances, which also contribute to eventual survival or death. Basic phenomena, present understanding of mechanism, and the existing and potential applications are briefly reviewed. PMID- 8496246 TI - Electromagnetic fields and cells. AB - There is strong public interest in the possibility of health effects associated with exposure to extremely low frequency (elf) electromagnetic (EM) fields. Epidemiological studies suggest a probable, but controversial, link between exposure to elf EM fields and increased incidence of some cancers in both children and adults. There are hundreds of scientific studies that have tested the effects of elf EM fields on cells and whole animals. A growing number of reports show that exposure to elf EM fields can produce a large array of effects on cells. Of interest is an increase in specific transcripts in cultured cells exposed to EM fields. The interaction mechanism with cells, however, remains elusive. Evidence is presented for a model based on cell surface interactions with EM fields. PMID- 8496247 TI - Fatty acyl-CoA binding activity of the nuclear thyroid hormone receptor. AB - Long-chain fatty acids and their acyl-CoA esters are potent inhibitors of nuclear thyroid hormone (T3) receptor in vitro. In the present study, we obtained evidence for acyl-CoA binding activity in the nuclear extract from rat liver. The activity sedimented at a position (3.5 S) identical with that of the T3 receptor, and the two activities sedimented together. Similarly, they coeluted on DEAE Sephadex. After partial purification of the receptor, it was again inhibited strongly by acyl-CoAs. Heat stability and a partial trypsin digestion of the receptor both suggested that the action site of oleoyl-CoA overlapped the T3 binding domain of the receptor. In addition, thyroid hormone receptor beta 1, synthesized in vitro, bound oleoyl-CoA specifically and its T3-binding activity was inhibited. The dissociation constant for oleoyl-CoA binding to the partially purified receptor was 1.2 x 10(-7) M. This value as well as its molecular size distinguished the nuclear binding sites from the cytoplasmic fatty acid/acyl-CoA binding proteins. Oleoyl-CoA had no effect on the glucocorticoid receptor, another member of the nuclear hormone-receptor superfamily. From these results, we propose that thyroid hormone receptor is a specific acyl-CoA binding protein of the cell nucleus. PMID- 8496248 TI - Differential expression of the chromosomal high mobility group proteins 14 and 17 during the onset of differentiation in mammalian osteoblasts and promyelocytic leukemia cells. AB - The expression of chromosomal proteins HMG 14 and HMG 17 during proliferation and differentiation into the osteoblast and monocyte phenotypes was studied. Cellular levels of HMG 14 and HMG 17 mRNA were assayed in primary cultures of calvarial derived rat osteoblasts under conditions that: (1) support complete expression of the mature osteocytic phenotype and development of a bone tissue-like organization; and (2) where development of osteocytic phenotypic properties are both delayed and reduced in extent of expression. HMG 14 and HMG 17 are preferentially expressed in proliferating osteoblasts and decline to basal levels post-proliferatively at the onset of extracellular matrix mineralization. In contrast, under conditions that are not conducive to extracellular matrix mineralization, HMG 14 is maximally expressed following the downregulation of proliferation. Consistent with previous reports by Bustin and co-workers [Crippa et al., 1990], HMG 14 and HMG 17 are expressed in proliferating HL-60 promyelocytic leukemia cells and downregulated post-proliferatively following phorbol ester-induced monocytic differentiation. However, differentiation into the monocyte phenotype is accompanied by reinitiation of HMG 17 gene expression. The results indicate that the levels of HMG 14 and HMG 17 mRNA are selectively down-regulated during differentiation. PMID- 8496249 TI - Isolation and characterization of deteriosomes from rat liver. AB - Deteriosomes, a new class of microvesicles, have been isolated from rat liver tissue. These microvesicles are similar to those isolated previously from plant tissue [Yao et al., Proc Natl Acad Sci USA 88:2269-2273, 1991] in that they are nonsedimentable and enriched in membrane catabolites, particularly products of phospholipid degradation. Liver deteriosomes range in size from 0.05 microns to 0.11 microns in radius. They are also much more permeable than microsomal membrane vesicles indicating that the deteriosome bilayer is perturbed. The data are consistent with the proposal that deteriosomes are formed from membranes by microvesiculation and that they represent an intermediate stage of membrane deterioration. Furthermore, liver deteriosomes were found to contain phospholipase A2 activity. This suggests that they not only serve as a means of moving destabilizing macromolecular catabolites out of membranes into the cytosol but also possess enzymatic activity. The fact that the specific activity of phospholipase A2 is higher in deteriosomes than in deteriosome-free cytosol suggests that some of the enzymatic activity traditionally assumed to be cytosolic may in fact be associated with deteriosomes. PMID- 8496250 TI - [Idiopathic segmental infarction of the great omentum. Value of celioscopy]. AB - Segmental infarction of the great omentum is a possible aetiology of acute abdominal pain. The diagnosis was difficult before operation and, generally the patient was operated upon with the diagnosis of appendicitis, or less often by laparotomy. The laparoscopy appears to be nowadays the ideal way of diagnosis, as this was the case in two of our patients. The treatment is also possible by laparoscopy (one of our patients). Generally speaking the laparoscopy should be of great help in the diagnosis of some acute abdominal pain, and could reduce the number of the so called non specific abdominal pain. PMID- 8496251 TI - [Comparative study of two methods of arterialization of foot veins in ischemic crisis]. AB - Between February 1974 and December 1991, a total of 28 arterializations of the venous network of foot were performed in patients with stage IIIB or IV arteriopathies presenting disseminated femoropopliteal and more distal lesions excluding revascularization by conventional arterial shunt operations. Two groups of patients could be distinguished. The first group, of 8 patients, underwent arterialization by shunt operation with end to end fistula at the distal part of leg and return blood emptying at the dorsal surface of foot (3 cases). The procedure was successful in 50% of cases after a mean follow up of 76 months. The intervention in the second group, of 20 patients, was by end to side fistula of foot after preoperative countercurrent phlebography and the use of a material better adapted for the destruction of the valves. Results were evaluated as successful in 70% of cases at 31 month follow up. After spontaneous closure of the fistula, the collateral circulation provoked by it was sufficient to conserve the acquired benefit. No deaths or cases of cardiac overload were reported as a result of the intervention. Comparative analysis of results showed that the use of the second procedure allowed amputation to be avoided in more than 2/3rds of cases, provided relief from pain, provoked healing of necrosed areas and permitted renewal of walking. The results of this study have demonstrated that venous arterialization of the foot by this method represents an interesting alternative in the saving of a limb destined for amputation. PMID- 8496252 TI - [Double trans-suture technique in colorectal surgical anastomosis. Apropos of 45 cases]. AB - The double trans-suture technique in colorectal anastomoses is an entirely mechanical one which consist of the transformation of two linear sutures in a circular one. During, 2 years, between March 1990 and March 1992, this technique was performed on 45 patients, of whom about two-third had a carcinoma of rectosigmoid. No postoperative mortality occurred. One patient developed an anastomatic stenosis, and another one a clinical leakage. The double trans-suture technique has not only the advantages of the double stapling technique but also avoids the incidents of performing a proximal purse. PMID- 8496253 TI - [Subxiphoid pericardiostomy and pericardioscopy. Value and indications apropos of a series of 25 cases]. AB - An experience of 25 subxiphoid pericardial windows with pericardioscopy in eleven cases is reviewed and presented. The operative indications in pericardial effusions result from hemodynamic compromise or from the need for etiologic criteria. Validated in its technical simplicity, its safety, its etiologic findings, its efficacy on immediate and delayed no recurrence of pericardial effusion, the low rate of late constrictive changes, this operative procedure is worth listing in the therapeutic know-how of a general surgeon. Indications in patients with suspected traumatic pericardial tamponade by chest wound are related. PMID- 8496254 TI - [Perineo-scrotal liposarcoma. Apropos of 3 cases]. AB - The authors report 3 rare cases of liposarcoma occurring in the perineal or paratesticular regions. They review literature data concerning this particular form of soft tissue sarcoma and emphasize on prognosis which depends mainly on its histo-pathologic type. PMID- 8496255 TI - [Peritonitis caused by a purulent cyst of the urachus in a young woman]. AB - Urachal cysts are not exceptional and are observed more often in children. In adults, they may become infected and cause clinical symptoms associating subumbilical midabdominal pain, fever, guarding and leukocytosis. Intraperitoneal rupture is exceptional (21 published cases) and only 7 cases have involved adult female patients. The authors report the case of a 27-year old woman with peritonitis caused by rupture of a suppurated urachal cyst, 6 cm in diameter, for which diagnosis was established by perioperative ultrasound. The surgical procedure used consisted of total excision of the urachus, the umbilico prevesical fascia and partial excision of the dome of the urinary bladder. Indeed, total excision is imperative because of the risk of malignant degeneration of this mass into an adenocarcinoma. PMID- 8496256 TI - [Parietal prosthetic mesh in the treatment of large incisional hernias]. AB - The repair of abdominal wall deficiencies has been simplified by the introduction of synthetic prostheses. The aim of this work was to describe the treatment of very large incisional abdominal hernias with a technique using a prosthetic mesh anchoring to the fibro-aponeurotic layers without closure the fascia. The procedure described has been used in 32 cases between 1974 and 1991 (15 male, 17 female). The median age was 62 years. All the patients were reexamined (median time: 4 years, range: 6 months-14 years). There was no operative mortality. Six patients had a subcutaneous seroma treated by multiple punctions. Three patients presented in the postoperative time a respiratory failure which necessitated artificial ventilation during 7 to 15 day. Two patients were reoperated, 6 months and 3 years after the first incisional hernia operation (1 cutaneous fistula, 1 hernia recurrence). Extremely large incisional hernias can be closed safely and effectively using this technique, without mortality and with a low morbidity. PMID- 8496257 TI - [Apropos of an angiosarcoma of the liver]. PMID- 8496258 TI - [Appendectomies. Mac Burney or laparoscopy? (100 cases)]. AB - The authors have compared their early (50 cases) experience on laparoscopic appendectomy for acute appendicitis with a control group treated by open approach. A teaching period is necessary to reduce the converting rate to an open procedure from 22% to 6% p = 0.05 and to obtain an equal median anesthesia time (39 vs 40 mn+/-16) ns). The mean post operative stay for open operation was 5-8 (range 3-23) days and for the laparoscopic route 3.3 (range 1-8) days (p < 0.005). The wound infection rate was 16% (n = 8) for open/ and 0% for laparoscopic appendectomy p = 0.001. The results suggest that emergency laparoscopic appendectomy should be explored further as an alternative to open surgery for acute appendicitis. PMID- 8496259 TI - [Mechanical resection of rectal tumors by transanal way under rectoscopic control. Results of a new surgical technique]. AB - The authors report the results of a new surgical procedure used in the treatment of rectal tumours. The mechanic devices Endo-Gia* 30 Multifire (Merlin Medical, SA, F-69672 Bron) was used in 8 cases (7 patients) in order to treat carcinoid tumours (n = 2) and villous polyp either with intermediate or severe dysplasia (n = 5) or transformed in Dukes A adenocarcinoma (n = 1). In 7 cases the follow-up was uneventful. In 1 case temporary rectal bleeding occurred. PMID- 8496260 TI - An acquired congenital disorder? PMID- 8496261 TI - Policy and practice. PMID- 8496262 TI - Osteoporosis management and hospital strategy. AB - As the patient population grows, strategies for preventing osteoporosis and for improving its management are urgently needed. Coordinating the efforts of existing hospital programs may help to meet these goals. PMID- 8496263 TI - Laparoscopic cholecystectomy with common duct exploration. PMID- 8496264 TI - Management of dilated cardiomyopathy. PMID- 8496265 TI - The mental status examination. PMID- 8496266 TI - Invasive management after myocardial infarction. PMID- 8496267 TI - Man's best friend. PMID- 8496268 TI - Gas chromatographic-mass spectrometric screening procedure for the identification of formaldehyde-derived tetrahydro-beta-carbolines in human urine. AB - A gas chromatographic-mass spectrometric method for the identification of 1,2,3,4 tetrahydro-beta-carboline and four metabolites extracted from urine is described. In a first step the substances, formed by reaction of formaldehyde with biogenic amines, were derivatized in aqueous solution with methyl chloroformate to eliminate an artificial formation of these compounds via condensation of endogenous indole ethylamines with aldehydes or alpha-keto acids during the work up procedure. This initial derivatization formed stable hydrophobic compounds and improved the extractability for a liquid-liquid extraction. Further clean-up was performed by solid-phase extraction on C18 sample preparation columns. The method can identify these compounds in the picogram range. PMID- 8496269 TI - Rapid and sensitive determination of piroxicam in rat plasma, muscle and skin by high-performance liquid chromatography. AB - A rapid and precise high-performance liquid chromatographic method for the determination of piroxicam in a variety of biological samples has been developed. A reversed-phase column, isocratic elution and ultraviolet detection were employed. Calibration curves were reproducible and highly linear, with correlation coefficients typically averaging over 0.992. The detection limit of the assay was 100 ng/ml for all biological samples examined (at a signal-to-noise ratio of 3:1). Validation of the method demonstrated a good sensitivity, accuracy and precision. The method has been adopted for a pharmacokinetic study in rats. PMID- 8496270 TI - Direct determination of ibuprofen and ibuprofen acyl glucuronide in plasma by high-performance liquid chromatography using solid-phase extraction. AB - A method for the simultaneous determination of ibuprofen and its labile, reactive metabolite, ibuprofen acyl glucuronide, in plasma is described. Reversed-phase high-performance liquid chromatography (HPLC) employed a C18 column using methanol-10 mM trifluoroacetic acid as the mobile phase with ultraviolet detection at 225 or 214 nm. It is essential that blood is handled rapidly and plasma is acidified upon collection prior to freezing. Plasma samples first are deproteinated with acetonitrile, the supernatant is diluted with phosphate buffer, and ibuprofen, ibuprofen glucuronide, and ibufenac (internal standard) are initially isolated by solid-phase extraction on C18 cartridges. Upon elution, the residue is evaporated, dissolved and injected onto the HPLC system. Recovery is 94 +/- 8 and 70 +/- 9% for ibuprofen glucuronide and ibuprofen, respectively. The measurable concentration range is linear from 0.1 to 10 micrograms/ml for ibuprofen glucuronide and from 0.5 to 100 micrograms/ml for ibuprofen. The method is satisfactory for the analysis of ibuprofen and ibuprofen glucuronide from pharmacokinetic studies in humans. The direct determination of ibuprofen glucuronide allows accurate measurement of this conjugate at low levels relative to the parent compound, ibuprofen, a distinct advantage compared to previously employed indirect methods. PMID- 8496271 TI - Measurement of naloxone in plasma using high-performance liquid chromatography with electrochemical detection. AB - A new sample preparation technique, solid-phase extraction employing the ion-pair reagent octyl sodium sulfate (OSS), was developed for the selective isolation of nanogram quantities of naloxone from human plasma. Plasma samples containing naloxone, OSS, buffer, and naltrexone (internal standard) were applied to octyldecylsilane (C18) cartridges, and the opiates were eluted with 100% methanol. An extraction efficiency of 90% was achieved. Extracts were then examined by reversed-phase high-performance liquid chromatography with electrochemical detection, with mobile phase composition adjusted to optimize separation and quantitation. An oxidizing potential of +0.93 V resulted in an assay sensitivity of 1.0 ng. Thus, plasma naloxone levels of ca. 20 ng/ml could be readily detected and quantified. The intra-assay coefficient of variation at plasma levels of 80 ng/ml was 7.2%. Plasma naloxone values obtained during a 5-h infusion of the drug (0.24 mg/min) in two normal human subjects were stable and reproducible. Thus, the method herein described is applicable to human studies employing naloxone infusion. PMID- 8496272 TI - Determination of ceftiofur and its metabolite desfuroylceftiofur in bovine serum and milk by ion-paired liquid chromatography. AB - A simple and sensitive liquid chromatographic method has been developed for the simultaneous determination of ceftiofur and its metabolite desfuroylceftiofur in bovine serum and milk. The method involved an ultrafiltration of diluted serum/milk with an equal volume of 50% acetonitrile through a 10,000 dalton molecular mass cut-off filter. Separation of ceftiofur and desfuroylceftiofur from the other serum/milk components was performed by ion-paired (octane and dodecanesulfonate) liquid chromatography using a reversed-phase column eluted with acetonitrile-water solution. The ultraviolet-visible absorbance of the column effluent was monitored in 200-350 nm range of a photodiode-array detector or at lambda max 289.6 nm for ceftiofur, lambda max 265.8 nm for desfuroylceftiofur and lambda max 271.4 nm for dimer of desfuroylceftiofur. Recoveries of ceftiofur from bovine milk spiked with 1 and 10 micrograms/ml were 95.9 and 97.0% with coefficients of variation of 3.69 and 2.51%, respectively. Recovery of ceftiofur from bovine serum spiked with 10 micrograms/ml was 90.4% with a coefficient of variation of 5.29%. A correlation coefficient of 0.9992 occurred with ceftiofur in aqueous solutions (n = 5, in duplicates). The limit of detection was estimated to be approximately 50 ppb (ng/ml). Additionally, this paper documents the presence of a ceftiofur metabolite in bovine serum under in vitro and in vivo conditions. The metabolite was identified as desfuroylceftiofur together with its dimer 3,3'-desfuroylceftiofur disulfide by thermospray liquid chromatography-mass spectrometry. PMID- 8496273 TI - Simultaneous determination of the enantiomers of pimobendan and its main metabolite in rat plasma by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the simultaneous analysis of the enantiomers of pimobendan and its main metabolite, with an n-hexane-ethanol acetic acid solvent system, has been developed. After solid-phase extraction from plasma, the enantiomers were separated from each other using a Sumichiral OA-4400 column, which is commercially available and contains a chiral stationary phase composed of (S)-proline and (S)-1-(alpha-naphthyl)ethylamine coated on silica. The enantiomers were detected with a fluorescence detector (excitation at 330 nm, emission at 415 nm). The intra- and inter-day precision studies showed good reproducibilities: the coefficients of variation were less than 10.3% for pimobendan enantiomers and 13.0% for metabolite enantiomers. The calibration curves were linear (r2 > 0.996) in the concentration range 1.25-200 ng/ml. The minimum measurable level was 125 pg per 100 microliters of plasma. The method was used in a preliminary pharmacokinetic study in three male rats after intravenous administration of racemic pimobendan (2 mg/kg). PMID- 8496274 TI - Quantification of amphetamine in urine: solid-phase extraction, polymeric-reagent derivatization and reversed-phase high-performance liquid chromatography. AB - The concentration of amphetamine was determined in urine using solid-phase extraction, polymeric-reagent derivatization, and reversed-phase high-performance liquid chromatography with ultraviolet detection. To remove a majority of acidic and neutral compounds in urine, a solid-phase extraction was first performed on a sample spiked with the internal standard, 1-methyl-3-phenyl-propylamine. Because amphetamine has a relatively low molar absorptivity, the base was derivatized with a polymeric 1-hydroxybenzotriazole reagent containing a 3,5-dinitrobenzoate active ester. The limit of detection is 14 ng/ml, and the limit of quantification is 47 ng/ml. The calibration curve is linear from 0.01 to 4.0 micrograms/ml. The pooled relative standard deviation is +/- 5.5% for eight urine samples measured in duplicate. The average relative error (bias) is +2.2% when compared to gas chromatography-mass spectrometry. PMID- 8496275 TI - Solid-phase separation of 14C-labelled urea and aminoisobutyric acid for membrane transport studies. AB - A sorbent extraction method has been developed for separating 14C-labelled urea and aminoisobutyric acid (AIB) in blood. The use of commercial solid-phase extraction cartridges containing aminopropyl-bonded silica provided a convenient and rapid separation of urea and AIB with better than 92% recovery of each and less than 5% cross-contamination. This allows these compounds, together with [3H]methylglucose, to be used as marker compounds for investigating three aspects of membrane transport. The facility to separate any two of the three compounds permits their simultaneous measurement, greatly increasing the amount of data obtainable from each in vivo preparation. PMID- 8496276 TI - Simple high-performance liquid chromatographic assay for polyamines and their monoacetyl derivatives. AB - A rapid reversed-phase high-performance liquid chromatographic method, using pre column derivatization with benzoyl chloride and ultraviolet detection at 254 nm, was developed for the simultaneous measurement of polyamines and their monoacetyl derivatives. Calibration curves were linear for concentrations from 1.25 to 25 nmol/ml. The method was employed to assay these compounds in chick embryo retina explants using organic solvent extraction and 1,7-diaminoheptane as an internal standard. This simple and sensitive method can be applied to routine determinations of these compounds in various biological samples. PMID- 8496277 TI - Preparation of the apoenzyme and holoenzyme forms of human 17 beta-hydroxysteroid dehydrogenase. AB - The apoenzyme and holoenzyme (NADP+ complex) of human placental 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) were prepared from affinity chromatography using various elutions by column liquid chromatography. The apoenzyme was obtained using NAD+ elution in a Blue-Sepharose column, followed by NAD+ separation on a Phenyl-Superose hydrophobic-interaction or a Mono Q anion exchange column. The 17 beta-HSD-NADP+ complex was prepared using NADP+ elution in a Blue-Sepharose column. The two forms have different A280/A260 ratios and are suitable for further study of enzyme-cofactor interactions. PMID- 8496278 TI - Simple column liquid chromatographic assay for serum neopterin. AB - A simple high-performance liquid chromatographic assay for serum neopterin with highly sensitive fluorimetric detection (limit 1 nM) is proposed. Comparison with results obtained by radioimmunoassay revealed a good correlation between the two techniques. The potential use of this method for the follow-up of liver transplant patients is discussed. PMID- 8496279 TI - Serum concentrations of retinol, d-alpha-tocopherol and beta-carotene: effects of storage at -70 degrees C for five years. AB - To investigate the effects of prolonged storage of serum samples at -70 degrees C on concentrations of micronutrients, we measured concentrations of retinol, d alpha-tocopherol, and beta-carotene in serum samples drawn in 1986. We compared values we measured in 1991 to values we obtained in 1986, using the same analytical methods. The relative concentrations obtained in 1991 (mean +/- S.D.) were: retinol 99.7 +/- 12.6% (n = 23), d-alpha-tocopherol 100.7 +/- 6.4% (n = 19), and beta-carotene 103.4 +/- 13.7% (n = 28). Using these techniques of sample preparation and high-performance liquid chromatographic analysis, we found that the effects of storage of serum at -70 degrees C for five years appear insignificant in a small population of patients. However, we did identify clinically important changes in concentration (> 20% difference) in several individual subjects. PMID- 8496280 TI - Determination of fluoxetine and norfluoxetine in human plasma by capillary gas chromatography with electron-capture detection. AB - A capillary gas chromatographic method with 63Ni electron-capture detection is reported for the determination of fluoxetine (Prozac) and its metabolite norfluoxetine in human plasma. A liquid-liquid extraction is used, followed by derivatization with heptafluorobutyric anhydride to increase the sensitivity of detection. A 30 m x 0.25 mm I.D. DB-17 capillary column resolves the compounds from endogenous matrix interferences. The limit of quantitation by this method is 5 ng/ml for each compound. Stability studies show that fluoxetine and norfluoxetine are stable in human plasma for up to 96 h at room temperature and up to one year at -20 degrees C. PMID- 8496281 TI - Reversed-phase high-performance liquid chromatography of ketorolac and its application to bioequivalence studies in human serum. AB - A reversed-phase high-performance liquid chromatographic assay was used to study the bioequivalence of the anti-inflammatory drug (+/-)-ketorolac in human volunteers. Following deproteinization of human serum with 5% zinc sulphate solution, ketorolac was chromatographed on a 10-microns octadecylsilica column using acetonitrile-water as mobile phase and ultraviolet detection at 313 nm. Under these conditions the method was reproducible with a coefficient of variation of less than 5%. The assay procedure was linear in the range 0.25-1.5 micrograms/ml, with a sensitivity of 0.01 micrograms/ml ketorolac. The recovery of ketorolac from serum ranged from 90 to 95%. PMID- 8496282 TI - Simplified method for quantitation of angiotensin peptides in tissue. AB - A simple method for extraction, separation, identification and quantitation of angiotensin-like immunoactivity from tissue is described. Homogenized acetic acid extracts of tissue samples were lyophilized and reconstituted in mobile phase. Separation was performed by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M aqueous ammonium phosphate buffer, pH 4.9. Elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II and III and the (1-7) and (3-8) peptides. Recoveries of labeled angiotensin peptide standards from the extraction step were > 90%. Radioimmunoassay of relevant peaks revealed detectable levels of angiotensin I-, II- and III-like immunoactivity in single rat hypothalami and brain stems. PMID- 8496283 TI - Molecular fractionation of gastric mucus component by high-performance liquid chromatography: application to pig gastric mucus in vitro and to human gastric mucus collected by aspiration during gastric endoscopy. AB - The glycoprotein molecular composition of antral and fundic adherent mucus has been studied by high-performance liquid chromatography on a silica gel column. Preliminary assays with pig gastric mucus allowed us to demonstrate the reproducibility of the method. The mucolytic activity of pepsin on this mucus demonstrates its ability to detect degradation of its glycoprotein components. This method was applied to control the state of pig antral mucosa that has previously been used in an in vitro antacid evaluation procedure, and also study human fundic and antral mucus collected by aspiration from normal and diseased stomachs during upper gastrointestinal endoscopy. Different elution profiles were obtained with these samples, depending on the presence of non-degraded or degraded mucus or due to the lack of mucus on the mucosa. PMID- 8496284 TI - Ion-pair extraction of histamine from biological fluids and tissues for its determination by high-performance liquid chromatography with fluorescence detection. AB - A procedure for the selective ion-pair extraction of histamine from various biological fluids and tissues by using the ion-pairing agent bis(2 ethylhexyl)hydrogen-phosphoric acid has been developed. This procedure enabled routine determination of histamine in plasma, urine and tissue samples of humans and rats by reversed-phase high-performance liquid chromatography with fluorescence detection using o-phthaldialdehyde. PMID- 8496285 TI - Synthetic carotenoids as internal standards for plasma micronutrient analyses by high-performance liquid chromatography. AB - A method is described for the synthesis of new carotenoids by transesterification of ethyl-beta-apo-8'-carotenoate. The rate of transesterification was temperature dependent with highest yields using primary alcohols. Reaction conditions were found avoiding Z isomerization. The structures of the new products were confirmed by ultraviolet, mass, 1H and 13C nuclear magnetic resonance spectroscopy. The synthetic carotenoids were used as internal standards for reversed-phase high performance liquid chromatographic (HPLC) analyses of lipid phase plasma micronutrients. Retention times for the trans-esterified products increased as a function of alcohol chain length allowing a choice of synthetic carotenoids for use as internal standards for carotenoid quantitation without interference with the detection of analytes during HPLC analysis. PMID- 8496286 TI - Reversed-phase high-performance liquid chromatographic method for the quantitation of endogenous folate catabolites in rat urine. AB - We describe a reversed-phase high-performance liquid chromatographic procedure for the analysis of rat urine for p-aminobenzoylglutamate (pABGlu) and its acetamido derivative (p-acetamidobenzoylglutamate, apABGlu). These two catabolites arise following the in vivo cleavage of the folate molecule at the C 9-N-10 bond. Known quantities of high-specific-activity tritiated forms of the catabolites are added as internal standards to aliquots of rat urine. Following preliminary sample clean-up on C18 Sep-Pak cartridges, including derivatisation in the case of pABGlu, the urinary extracts are quantitated by HPLC. The present assay makes possible for the first time the determination of endogenous folate breakdown in the rat. PMID- 8496287 TI - Analysis of complex mixtures of phospholipid classes from cell membranes using two-dimensional thin-layer chromatography and scanning laser densitometry. AB - Increasing recognition of the important roles served by membrane phospholipids in cellular metabolic and signal transduction processes has stimulated interest in examining potential phospholipid abnormalities in patients with psychiatric disorders. This report describes a method, based on several novel modifications of existing techniques, for concurrently analyzing nanomolar amounts of nine phospholipid classes in a single aliquot of membrane extract. With this method, diverse phospholipid classes are first separated by two-dimensional thin-layer chromatography, and then determined using two-dimensional scanning laser densitometry. The method is able to quantitate even small amounts of specific phospholipid classes, corresponding to < 10 ng of lipid phosphorus. The sensitivity of this method allows it to be readily applied to clinical studies involving membranes from cell types that are obtainable only in small quantities. PMID- 8496288 TI - Gas chromatographic characterization of free D-amino acids in the blood serum of patients with renal disorders and of healthy volunteers. AB - A capillary gas chromatographic method, using the chiral stationary phase Chirasil-L-Val, after treatment and isolation with Dowex 50W X8 cation exchanger and conversion into trifluoroacetyl-1-propyl esters or pentafluoropropionyl-1 (or 2)-propyl esters, has been developed for the determination of the relative amounts of free D-amino acids in the blood serum of eighteen patients with renal failure (continuous ambulatory peritoneal dialysis (CAPD), n = 11; hemodialysis, n = 5; nephrotic syndrome, n = 2) and compared with data obtained from healthy volunteers (n = 5). Significant amounts of D-Ala (0.5-13%) and D-Asx (1.5-7.7%; Asx = Asp + Asn) were found in all serum samples. D-Ser was detected in the serum of all patients with renal disorders and, in addition, D-Pro (0.6-2.5%) was found in the serum of all patients undergoing hemodialysis and with nephrotic syndrome. D-Ser (2.9-3.1%) and D-Pro (0.6-0.9%) were also found in the samples of three volunteers. D-Leu (1.2-1.7%) was present in three patients with CAPD, and D-Glx (0.3-1.3%; Glx = Glu + Gln) was present in eight of eighteen patients with renal malfunction. Linear regression analysis of the relative amounts of D-amino acids and the serum creatinine levels of all donors revealed positive correlation factors for D-Asx (r = 0.748) and D-Ser-(r = 0.667), but not for D-Pro and D-Ala. Remarkably high amounts of D-Ser (12.1 and 19.8%) were found in two hemodialysates investigated. Participation of intestinal bacteria and nutrition are discussed as possible sources of serum D-amino acids. An increase of some D amino acids in the serum of patients with renal diseases might be explained, in part, by decreased activity of renal D-amino acid oxidase. PMID- 8496289 TI - Immunoaffinity chromatography combined with gas chromatography-negative ion chemical ionisation mass spectrometry for the confirmation of flumethasone abuse in the equine. AB - Immunoaffinity chromatography using a synthesised immunosorbent was used to extract tritiated dexamethasone (with dexamethasone carrier) from equine urine at a recovery of 81.7 +/- 8.4% (mean +/- S.D.). A method utilising this procedure coupled to cool on-column injection gas chromatography-negative ion chemical ionisation mass spectrometry is also described for the confirmation of low levels of flumethasone in equine urine samples. PMID- 8496290 TI - Determination of quinine in serum, plasma, red blood cells and whole blood in healthy and Plasmodium falciparum malaria cases by high-performance liquid chromatography. AB - A normal-phase high-performance liquid chromatographic method using dichloromethane-methanol-1 M perchloric acid (100:9:0.4, v/v) at a flow-rate of 0.8 ml/min on a Zorbax-Sil column with fluorescence detection has been developed for the separation of quinine and quinidine from other antimalarials. Within-day and day-to-day coefficients of variation averaged 0.74 and 7.56%, respectively. The extraction recovery of quinine for plasma, serum, red blood cells and whole blood (filter paper) was 88.13, 87.12, 78.0 and 77.5%, respectively. The method is capable of separating quinine from dihydroquinine, a compound usually found as an impurity in authentic quinine samples. The method has been used for the determination of quinine in plasma, serum, red blood cells and whole blood (filter paper) of six healthy and twenty Plasmodium falciparum malaria cases. The average quinine concentration in P. falciparum malaria cases was three to four times higher than that in healthy volunteers. Quinine was absorbed much less in red blood cells than in plasma or serum. PMID- 8496291 TI - Liquid chromatographic determination of beta-cyclodextrin derivatives based on fluorescence enhancement after inclusion complexation. AB - A liquid chromatographic method using fluorescence detection for the determination of beta-cyclodextrin (beta CD) and its derivatives is presented. The chromatographic system is based on size-exclusion chromatography with the addition of the fluorophoric compound 1-naphthol to the mobile phase. Detection is based on fluorescence enhancement caused by the formation of inclusion complexes. By incorporating 10(-4) M 1-naphthol in the mobile phase, detection limits of 90, 27, 370 and 37 pmol were obtained for beta CD, hydroxypropyl-beta CD, trimethyl-beta CD and dimethyl-beta CD, respectively. The method was applied to the determination of dimethyl-beta CD in urine: the minimum detectable concentration was 0.2 microgram/ml after preconcentration of 10 ml of urine. PMID- 8496292 TI - Detection of dengue virus by in situ hybridization. AB - A non-radioactive in situ hybridization protocol was developed for the detection of dengue virus RNA in fixed tissues and cells. For this purpose a riboprobe was constructed from a 39 base sequence, from the capsid protein coding region of the genome, which is conserved in the four dengue serotypes. The ability of this probe to specifically detect dengue RNA from each serotype was confirmed on brain sections from infected mice. Dengue viral RNA was also detected in in vitro infected human primary endothelial cells which release infectious virus without showing gross cytopathic effect. With clinical samples dengue viral RNA was detected in some preparations of white blood cells from dengue fever patients and in thymus autopsy sections following suspected death from dengue shock syndrome. For dengue samples of undetermined serotype the sensitivity of the short probe was compared to that of an equimolar mixture of long (260 base) probes from the envelope coding region of the four dengue serotypes, provided by Dr. V. Deubel. In those samples examined, sensitivity of the long probe mixture was greater and higher numbers of infected cells were detected. PMID- 8496293 TI - HIV-1 plasma viraemia quantification: a non-culture measurement needed for therapeutic trials. AB - Accurate measures of inhibition of virus replication are needed to evaluate the efficacy of antiretroviral agents in large clinical trials. We describe an accurate, economical and rapid method for the direct detection and quantification of cell-free human immunodeficiency virus type -1 (HIV-1) in serum or plasma. The method includes affinity capture of the virus by latex microparticles coated with HIV-1 envelope-specific antibodies, reverse transcription primed by an HIV-1 specific oligonucleotide and amplification by nested PCR of the synthesised cDNA. We show that the method can be applied to large numbers of serum samples, is reproducible and is highly applicable to the monitoring of viral load in HIV-1 infected patients, especially during the investigation of drug efficacy. PMID- 8496294 TI - Comparative analysis of scrapie agent inactivation methods. AB - A scrapie-infected hamster brain homogenate was subjected to several different potential inactivation methods. Methods included autoclaving for various lengths of time, either alone or in combination with different concentrations of sodium hydroxide or LpH, an aqueous acid phenolic derivative (Calgon Vestal Laboratories in St. Louis, MO). Inactivation treatments utilizing either NaOH or LpH alone were also evaluated. It was determined that several of the treatments inactivated all of the detectable infectivity. PMID- 8496295 TI - Efficient parvovirus B19 DNA purification and molecular cloning. AB - A simple and efficient method of purification and molecular cloning of Parvovirus B19 DNA directly from small quantities of viremic sera was developed. Purified virions were lysed in annealing conditions, then viral DNA purification in double strand (ds) DNA form was achieved using an affinity DNA binding matrix. Affinity purification yielded a consistently high recovery of viral DNA. Using affinity purified ds viral DNA, we efficiently and stably cloned the complete coding internal unique sequence of B19 DNA. In our cloning strategy AatII and BamHI restriction endonuclease sites were exploited. This permitted cleavage of the 5.0 kbp AatII fragment in two AatII-BamHI fragments which could be efficiently cloned in a directional way in pUC18 plasmid vector. The availability of the two cloned AatII-BamHI fragments thus allowed the construction of a full length clone in a single ligation reaction. PMID- 8496296 TI - Use of a rapid test and an ELISA for HIV antibody screening of pooled serum samples in Lubumbashi, Zaire. AB - Pools with a size of 3 and 5 were prepared by mixing one HIV confirmed HIV-1 seropositive serum with either 2 or 4 HIV seronegative sera at the Regional HIV Laboratory in Lubumbashi, Zaire. These pools were assessed in a blind fashion by ELISA (Vironostika anti-HTLV-III microELISA system, Organon Technika). Similarly constituted pools of 3 samples were assayed by a rapid test with visual reading (HIVCHEK 1 + 2, Dupont de Nemours). With the HIVCHEK, pooling was achieved on the test device itself by dropping consecutively 3 different serum samples on the devices's membrane. After the last serum was soaked in, wash fluid and conjugate were added. Results of the pooling experiments were compared with testing sera individually. The ELISA results from pools and from individual tested samples matched completely if, and only if, the final dilution of individual samples in the reagent medium was the same as recommended by the manufacturer for testing of individual samples. With the HIVCHEK a sensitivity of 99-100% was obtained with pooled sera. Both approaches seemed sensitive enough to enable their use for screening of blood donors and patient management, but a prospective study to validate these preliminary results is necessary. PMID- 8496297 TI - Clinical review 45: Clinically nonfunctioning pituitary adenomas. PMID- 8496298 TI - Characterization of proinsulin-like growth factor-II E-region immunoreactivity in serum and other biological fluids. AB - Insulin-like growth factor-II (IGF-II) purified from human serum consists of 67 amino acids. However, mRNA sequence predicts a long carboxy-terminal extension (E region), which on translation would yield a bigger IGF-II prohormone than the peptide isolated from serum. A peptide containing the predicted IGF-II prohormone sequence extending from Asp69 to Tyr84 (E-II) was synthesized by the solid state method and used to generate a polyclonal antiserum. Using this E-II antiserum, a specific RIA for IGF-II prohormone forms was developed. [125I]E-II was used as tracer, and synthetic E-II was used for the standard curve. The antiserum was highly sensitive and specific for E-II. It also recognized pro-IGF-II-E21, a 9.8 kilodalton (kDa) synthetic peptide which consisted of IGF-II plus the first 21 amino acid sequence of the IGF-II E-peptide region. Human biological fluids assayed included serum and amniotic, seminal, and cerebral spinal fluids. Sera from patients with chronic renal failure (CRF) and nonislet cell tumor hypoglycemia (NICTH) had the highest levels of E-II immunoreactivity. Amniotic and seminal fluids and acromegalic plasma had intermediate levels. E-II levels in normal, cord, and pregnancy sera were low, but measurable. To further characterize the molecular forms of the apparent E-II immunoreactivity, sera pooled from five normal subjects, five CRF patients, and one patient with NICTH were chromatographed separately over a Sephadex G-50 column in formic acid. With all samples, there was a major peak of E-II immunoreactivity at about 15 kDa, consistent with the predicted size of the IGF-II prohormone. There was a second smaller peak at about 10 kDa in NICTH serum. With CRF serum, there was a prominent peak at 3 kDa, which probably consisted of breakdown products of the IGF-II E-peptide region. The 15-kDa peak was highest in NICTH serum. With all three samples, IGF-I eluted in a single peak at about 7 kDa and was low in NICTH serum. There were two peaks of IGF-II. The first coincided with the peak of E-II at 15 kDa, while the second comigrated with IGF-I. By Western immunoblot analysis, the E-II antiserum detected pro-IGF-II-E21 as a band at 10 kDa, but it did not recognize 7.5-kDa recombinant IGF-II, which did not have the E-peptide region.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8496299 TI - Evidence for increased androsterone metabolism in some normoandrogenic women with acne. AB - Increased androgen production from the ovary, adrenal or locally in skin has been implicated in the pathogenesis of acne. Recent data have provided evidence that androsterone (Ao) metabolism is exaggerated in acne and serum metabolites of Ao differentiate between acne and hirsutism in hyperandrogenic women. Here we have extended these studies to normoandrogenic women who have moderate to severe acne. We measured serum ovarian and adrenal androgens as well as the glucuronide and sulfate metabolites of Ao and 3 alpha-androstanediol which reflect, in part, peripheral androgen action. In a group of 15 well-selected normoandrogenic patients with acne, both serum Ao glucuronide (G) and Ao were elevated (P < 0.01; P < 0.05). The ratios of Ao G to androgen precursors of both ovarian and adrenal origin were elevated as was the ratio of Ao G/Ao (P < 0.05). These data suggest that increased Ao metabolism is a specific abnormality found in both normoandrogenic and hyperandrogenic women with acne. Our findings also provide a rationale for antiandrogen therapy at least in some normoandrogenic women with acne. PMID- 8496300 TI - Differential expression of messenger ribonucleic acids encoding insulin-like growth factors and their receptors in human uterine endometrium and decidua. AB - During the menstrual cycle, the endometrium undergoes characteristic changes in response to circulating sex steroids. Intense mitotic activity of glands and stroma occurs in the proliferative (estradiol-dominant) phase, and glandular secretion and stromal differentiation in the secretory (progesterone-dominant) phase. The insulin-like growth factors (IGF-I and IGF-II) promote cellular growth and differentiation and have been proposed to participate in these cyclic endometrial events, acting as mediators of steroid hormones. The objective of this study was to determine whether the messenger RNAs (mRNAs) encoding the IGF peptides and the type I and type II IGF receptors are differentially expressed in human endometrium during the menstrual cycle and in early pregnancy. A solution hybridization ribonuclease protection assay, using 32P-labeled riboprobes for IGF I, IGF-II, and beta-actin (control), revealed IGF-I gene expression primarily in proliferative and early secretory endometrium and abundant IGF-II gene expression in mid-late secretory endometrium and early pregnancy decidua. Northern analysis, using IGF-I and IGF-II complementary DNA probes, revealed multiple IGF-I mRNAs [2 7.6 kilobase (kb)], expressed primarily in proliferative and early secretory endometrium, and IGF-II mRNAs (1.4-6.0 kb), expressed primarily in secretory endometrium and in early pregnancy decidua. The 7.6-kb IGF-I mRNA and the 6.0-kb IGF-II mRNA were most abundantly expressed. IGF-IEa and IGF-IEb mRNA splicing variants were present in a ratio of about 9:1, respectively. Type I and type II IGF receptor gene expression in endometrium was investigated using specific riboprobes and the ribonuclease protection assay. Messenger RNAs encoding both receptors were more abundantly expressed in the secretory phase and during early pregnancy, compared to the proliferative phase. These results show that mRNAs encoding the IGF peptides and their receptors are differentially expressed in human endometrium, depending on the steroid hormone milieu. The preferential expression of IGF-I mRNA in the proliferative phase supports the hypothesis that IGF-I is an estromedin in human endometrium. The expression of endometrial IGF-II mRNA in the mid to late secretory phase and in early pregnancy supports a role for IGF-II in differentiative functions of the endometrium, perhaps including endometrial tissue shedding in the menstrual cycle or remodeling during early pregnancy. PMID- 8496301 TI - Neuroendocrine changes in luteal function in patients with premenstrual syndrome. AB - The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6% vs. 187.1 +/- 126.7%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder. PMID- 8496302 TI - Reduced expression of glucocorticoid receptor levels in human osteoarthritic chondrocytes. Role in the suppression of metalloprotease synthesis. AB - Glucocorticoid occupancy of a large percentage of glucocorticoid receptor (GR) is necessary for the suppression of matrix metalloprotease synthesis by human articular chondrocytes. In this study, we evaluated the levels of GR binding, cellular GR protein, and messenger RNA expression in both normal and osteoarthritic (OA) human articular chondrocytes and compared the degree of suppression of collagenase synthesis by glucocorticoids in cultures of the two cell types in order to investigate whether or not the GR system played an important role in the pathophysiology of OA. By radioreceptor binding assay, we recorded 56,320 +/- 8,230 sites per cell (mean +/- SE, n = 9) in primary cultures of normal chondrocytes and 27,480 +/- 14,240 sites in OA cells (n = 10, P < 0.0001). Equilibrium dissociation constant (Kd) values did not vary between normal (12.4 +/- 1.4 nmol/L) and OA (13.0 +/- 1.8 nmol/L). Subculturing of primary OA chondrocytes resulted in the up-regulation of the number of GR binding sites per cell to values comparable to those obtained in normal chondrocytes. Analysis of protein-immuno dot-blots of cytosolic extracts from normal (n = 4) and OA chondrocytes (n = 4) revealed that the former cytosols contained a 1.9 +/- 0.2 (P < 0.05) higher relative density of GR protein than the latter. By comparing the optical densities of GR-polymerase chain reaction products generated from normal (n = 6) and OA (n = 9) chondrocyte total RNA (normalized using an internal standard, glyceraldehyde phosphate dehydrogenase), we established a relative ratio, normal/OA, of 1.4. Experiments comparing the biological responsiveness of normal and OA chondrocytes to glucocorticoid suppression of interleukin-1-stimulated metalloprotease synthesis showed that dexamethasone inhibited collagenase synthesis in a dose-dependent manner with an IC50 of 6.3 +/- 1.2 x 10(-10) mol/L (n = 5) in normal cells while an IC50 of 5.0 +/- 0.4 x 10(-9) mol/L (P < 0.05) was recorded using OA (n = 5) chondrocytes. The results suggest that OA chondrocytes express fewer GR than normal cells as a result of a decrease in specific gene expression. The decreased responsiveness of OA cells to circulating glucocorticoids may be among the factors responsible for an increased level of metalloprotease synthesis by chondrocytes in OA cartilage. PMID- 8496303 TI - Differential regulation of serum growth hormone (GH)-binding protein during continuous infusion versus daily injection of recombinant human GH in GH deficient children. AB - Serum GH-binding protein (GHBP) was evaluated in 2 randomly divided groups of prepubertal children presenting with idiopathic GH deficiency and receiving recombinant human GH, either continuously by sc infusion (group 1) or as 1 daily sc injection (group 2). After the first 6 months, group 1 switched from continuous infusion to daily injections for the following 6 months. There was no significant difference in clinical data, GH values, or GHBP levels between the 2 groups before treatment. During the first 6 months, GHBP levels increased in all except 1 of the 8 children in group 1 from 8.6% to 16.9% after 3 months and 22.5% after 6 months. The increment factor ranged from 1.1-7.9, with wide individual variations. In group 2, the mean variation in GHBP was from 8.3-8.2% after 3 months and 10.7% after 6 months. Only 2 of the 10 children in this group showed a significant increase in GHBP levels. During the second period, group 1 maintained their GHBP levels, whereas the 2 children in group 2 tended to a continued increase in their GHBP levels. There was no correlation with the increase in growth velocity, as children in both groups grew equally well, but higher insulin like growth factor-I levels were found in group 1, although the difference between the two groups was not significant. These data show that GH can increase GHBP levels and that there is a differential effect depending on the mode of GH administration, although the reason for and the role of such regulation remains to be explained. PMID- 8496304 TI - Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. AB - To evaluate the effects of obesity on the hypothalamo-pituitary-testicular axis, we compared total and free (FT) testosterone (T), androstenedione, dehydroepiandrosterone and its sulfate, and 5 alpha-androstane-3 alpha, 17 beta diol glucuronide, and estradiol levels in a group of 35 obese [body mass index (BMI), > 30] men (aged 17-61 yr) to levels in a nonobese control group. We observed a highly significant negative correlation (P < 0.001) between plasma (F)T levels and BMI and a significant positive correlation (P < 0.01) between E2 levels and BMI. There were no differences between the obese and the nonobese men in levels of androstenedione, dehydroepiandrosterone sulfate, and 5 alpha androstane-3 alpha, 17 beta-diol glucuronide. Insulin levels were significantly higher in obese men and were significantly (P < 0.02) correlated with the waist hip girth ratio. To evaluate the role of the hypothalamo-pituitary complex in the decreased (F)T levels in obese men, diurnal (0800-2000 h) LH pulsatility was studied in eight obese middle-aged men and eight age-matched controls. The pulsatility of plasma cortisol levels was also studied. Whereas LH pulse frequency was similar in the obese and control subjects, mean diurnal LH levels, mean diurnal LH pulse amplitude, and the sum of all diurnal LH pulse amplitudes and secretory masses were significantly lower in the obese than in the controls. Moreover, there was a highly significant correlation between the sum of LH pulse amplitudes and plasma (F)T levels. This decrease in LH pulse amplitude is not an isolated phenomenon of hypothalamo-pituitary dysfunction in obese men, because the pulse amplitude of plasma cortisol levels was also decreased. The decreased LH pulse amplitude together with the normal respond of Leydig cells to hCG stimulation reported in the literature suggest by inference that the decreased FT levels in obese men are the consequence of a hypogonadotropism. The decreased LH pulse amplitude and the decreased amplitude of cortisol pulses, and hence probably of ACTH pulses, point toward a general alteration of hypothalamo pituitary function in obese men. PMID- 8496305 TI - Androgen receptor blockade with flutamide enhances growth hormone secretion in late pubertal males: evidence for independent actions of estrogen and androgen. AB - Exogenous and endogenous sex steroid hormones influence GH secretion. To test the relative importance of androgens in the enhancement of GH secretion, we administered flutamide (a potent androgen receptor blocker) to six late pubertal males. Blood samples for GH (and LH) were obtained at 10-min intervals for 24-h periods after 3 days of flutamide and during the untreated state. Waveform specific, multiple-parameter deconvolution analysis was employed to assess secretory and elimination dynamics for GH. Androgen receptor blockade was confirmed by significant increases in 24-h mean LH concentrations and in total 17 beta-estradiol and free testosterone levels in the serum. Mean serum GH concentrations (24-h) also increased (P < 0.001) during androgen receptor blockade (mean +/- SEM, 2.9 +/- 0.3 vs. 1.8 +/- 0.3 micrograms/L); this was associated with an increased (P < 0.001) GH production rate [152 +/- 15 vs. 93 +/ 16 micrograms/liter of distribution volume (Lv)/24 h]. The enhanced GH secretion during flutamide administration was a result of both increased mass of GH released per secretory burst (12.0 +/- 1.4 vs. 8.4 +/- 1.0 micrograms/Lv; P < 0.005) and increased maximal rate of GH secretion (0.39 +/- 0.04 vs. 0.30 +/- 0.03 micrograms/Lv/min; P < 0.05), as well as a small increase in the number of detectable secretory bursts (12 +/- 1 vs. 10 +/- 1/24 h; P < 0.05). There was no significant change in either the serum half-life of GH or in the half-duration of GH secretory bursts during androgen receptor blockade. We speculate that the augmentation of GH secretion observed during antagonism of androgen action in late pubertal males is a result of increased stimulation of estrogen receptor mediated pathways. Alternatively, androgens may exert a tonic inhibition of GH secretion which can be abolished by androgen receptor blockade. PMID- 8496306 TI - Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans. AB - Measurement of melatonin secretion throughout the night provides an index of net noradrenergic activity mediated by postsynaptic beta-adrenergic receptors in the pineal gland. Reduced melatonin secretion in some patients with depression might be related to reduced net noradrenergic function. However, a dysregulation in serotonin function has also been implicated in the pathophysiology of depression. The essential amino acid tryptophan is the precursor for both serotonin and melatonin production. To determine the effects of serotonin function on nocturnal melatonin secretion, eight healthy volunteers underwent active and sham tryptophan depletion in a randomized, double-blind fashion. Blood samples for melatonin and free and total tryptophan were obtained before and after the depletion. Acute tryptophan depletion decreased free and total plasma tryptophan levels to less than 20% of baseline levels. Melatonin secretion, expressed as area under the curve, was decreased in all eight subjects after tryptophan depletion when compared to sham depletion. These results suggest that reduced plasma tryptophan levels, and presumably brain serotonin concentrations, decrease nocturnal melatonin secretion in humans. Additional studies investigating the relationship between serotonin metabolism and pineal function in humans appear warranted. PMID- 8496307 TI - Inhibition of thyroxine transport into cultured rat hepatocytes by serum of nonuremic critically ill patients: effects of bilirubin and nonesterified fatty acids. AB - We investigated bilirubin and oleic acid as causes of low plasma T3 in nonuremic critically ill patients with gross changes in serum thyroid hormone levels (T4, < or = 60; T3, < or = 1.1; rT3, > or = 0.45 nmol/L) and elevated bilirubin concentrations (> or = 33 mumol/L). Iodide production from [125I]T4 was inhibited by 42% when rat hepatocytes in primary cultures were incubated with 10% serum from these patients. The mean serum concentration of albumin was reduced by 41%, while the concentrations of bilirubin and nonesterified fatty acids (NEFA) were increased by 2022% and 115%, respectively, in the patients. The molar ratios of bilirubin/albumin and NEFA/albumin in the patients were 0.42 and 3.18, respectively. Addition of oleic acid (50-400 mumol/L) and bilirubin (3-130 mumol/L) to 10% normal human serum (albumin, 70 mumol/L; NEFA, 54 mumol/L; bilirubin, 1.1 mumol/L) progressively inhibited the production of iodide by rat hepatocytes. The decreased iodide production was presumed to be caused by inhibition of T4 transport into hepatocytes. The deiodination of rT3 by rat liver microsomes was unaltered by free bilirubin and free oleic acid concentrations up to 0.1 mumol/L. These free concentrations are at least 1 order of magnitude higher than that attained in nonthyroidal illness. The inhibition of iodide production by the sera of critically ill patients (n = 12) was significantly correlated with the molar ratios of bilirubin/albumin (r = 0.72; P < 0.01) and NEFA/albumin (r = 0.58; P < 0.05). Extensive dialysis or treatment of the sera with charcoal did not completely remove the inhibitory activity on iodide production. Serum concentrations of indoxyl sulfate, 3-carboxy-4-methyl-5-propyl 2-furan propanoic acid, and hippuric acid in the critically ill patients (other known T4 transport inhibitors into hepatocytes) were similar to those in the normal subjects. This study together with the well known effects of carbohydrate on T3 neogenesis suggest that elevated bilirubin and NEFA and the low albumin level in non-uremic critical illness may be at least partly responsible for the T4 transport inhibition in T3-producing tissues (e.g. the liver) and, thus, the low plasma T3 levels in these critically ill patients. The question of whether inhibitors of T4 transport into the hepatocytes are also present in other patients with nonthyroidal illness who show only mild changes in thyroid hormone levels and have low concentrations of bilirubin and NEFA remains to be determined. PMID- 8496308 TI - Luteinizing hormone pulse characteristics in early pubertal boys are the same whether measured by radioimmuno- or immunofluorometric assay. AB - We tested the hypothesis that the improved sensitivity of immunofluorometric (IFMA) assays will lead to an increase in the number of detectable LH pulses compared to RIA in early pubertal boys, in whom LH secretion is low. To test this hypothesis we determined plasma LH concentrations in six pubertal boys (bone age, 12-16 yr) by IFMA and compared the results to RIA data reported previously. Each boy was given an infusion of saline, followed 1 week later by an infusion of testosterone (T; 960 nmol/h) for 33 h starting at 1000 h. Starting at 1200 h, blood was obtained every 15 min for LH determinations (RIA and IFMA) and every 30 min for T measurements. At the end of both studies, responses to GnRH (250 ng/kg) were assessed. The assay sensitivities for LH by RIA and IFMA (Delfia hLH Spec Pharmacia Diagnostics ENI, Columbia, MA) were 1.0 and 0.05 IU/L, respectively. LH pulses were identified by three independent pulse detection programs: Detect, Cluster, and Kushler-Brown. The correlation for LH values as measured by RIA and IFMA was highly significant (r = 0.81). There was a poor correlation between LH values determined by IFMA and RIA when LH values within 4 times the SD of each assay sensitivity were compared (r = 0.08; P = NS). T infusion suppressed LH pulse frequency by 40% and 66%, as determined by RIA and IFMA, respectively (P = NS). Using the Detect program, during the complete study in all 6 boys, 117 pulses of LH were identified by RIA and 93 by IFMA (79% ratio of detection IFMA/RIA). During saline infusion there were 73 vs. 69 LH pulses (94%), while during T infusion there were 24 vs. 44 LH pulses (55%), as detected by IFMA vs. RIA, respectively. Administration of naloxone did not accelerate LH pulse frequency during T infusion, as determined by either method. Changes in pituitary responses to exogenous GnRH also showed similar trends of augmentation by T infusion by both methods. We conclude that the use of IFMA does not lead to the anticipated increase in the detectability of LH pulsatility. Actually, fewer LH pulses were identified by IFMA in this group of boys. We speculate that this is due to the increased specificity of the IFMA assay. More significant was the finding that the physiological interpretation of the effects of T and naloxone on LH pulse frequency and responses to GnRH did not change whether LH was measured by RIA or IFMA. PMID- 8496309 TI - Properties of growth hormone and prolactin hypersecretion by the human infant on the day of birth. AB - The neonatal period is the only interval in postnatal life characterized by physiologically elevated plasma concentrations of GH and PRL, two hormones of common origin. To study the secretion of GH and PRL on the day of birth, we obtained at regular intervals (every 20 min for 6 h) blood from seven polycythemic newborns (gestational age 34-41 weeks; birthweight 1600-3960 g; postnatal age 6-23 h) during a therapeutic, standardized, isovolumetric, partial exchange transfusion. Serum GH concentrations were measured by RIA and PRL levels by immunoradiometric assay. Deconvolution analysis of the profiles revealed that all infants displayed a pulsatile pattern of amplified GH release (range 9-191 micrograms/L). Bursts of GH secretion occurred at a median interval of 73 min. The median serum GH half-life was 18 min. All infants had continuously elevated serum PRL concentrations (range 86-191 micrograms/L) and none appeared to release PRL episodically. There was no significant cross-correlation between the secretion of GH and PRL. Mean serum GH concentrations during the 6-h study were higher than in cord serum at birth, whereas PRL and insulin-like growth factor-1 levels were lower than at birth. In conclusion, the neonatal hypersomatotropism appears to be characterized by high-amplitude, high-frequency, pulsatile secretion of GH without a prolonged GH half-life, whereas hyperprolactinemia seems to result from GH-independent, continuous PRL release. The immediate postnatal rise of GH secretion in the human newborn may be related to decreased inhibition by circulating insulin-like growth factor-1. PMID- 8496310 TI - Short-term fasting is a mechanism for the development of euglycemic ketoacidosis during periods of insulin deficiency. AB - To determine the etiology of euglycemic ketoacidosis, the effect of a 32-h fast on the rate of metabolic deterioration was examined in a group of 10 healthy subjects with type I diabetes mellitus. Patients were studied during 5 h of insulin withdrawal after 8 h (postprandial) and 32 h (fasted) of food deprivation. Study parameters included substrate levels, electrolytes, counterregulatory hormone levels, and rates of glucose and glycerol turnover. In the fasted state, mean peak plasma glucose concentrations were significantly lower than those in the 8-h postprandial state (13.3 +/- 1.6 vs. 17.4 +/- 1.4 mmol/L, respectively; P < 0.05), and mean rates of glucose production were also significantly lower at all time points in the fasting state. The rate of development of ketosis was significantly more rapid during insulin deficiency after a fast (8.82 +/- 0.63 vs. 6.23 +/- 0.30 micro/L.min; P < 0.05), while plasma nonesterified fatty acids and glycerol turnover showed a biphasic response to insulin withdrawal, which was also more robust after a fast. Metabolic acidosis, as reflected in the rate of decrease in serum bicarbonate concentration, was more severe after 32 h of fasting than in the postprandial state (mean nadir, 15.4 +/- 0.9 vs. 18.6 +/- 0.5 mmol/L; P < 0.001). In contrast to values in the postprandial state, serum glucagon levels rose during insulin withdrawal in the fasting state, and plasma norepinephrine levels also correlated positively with the ongoing metabolic decompensation. Other counterregulatory hormones did not differ significantly in the fasted vs. postprandial states in these short term metabolic studies. We conclude that a fast of moderate duration, such as might be expected to occur during the development of diabetic ketoacidosis, predisposes patients with type I diabetes to euglycemic ketoacidosis during periods of insulin deficiency. Furthermore, decreased rates of hepatic glucose production are responsible for the lower plasma glucose values observed during a fast. The development of ketosis continued progressively in both conditions, but the rate of rise of plasma ketones was increased in the fasted state. This accelerated development of ketosis may be attributable to the effects of elevated levels of glucagon and/or catecholamines on lipolysis. PMID- 8496311 TI - Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus. AB - GH-releasing peptide (GHRP; SK&F 110679) is a synthetic hexapeptide that specifically stimulates GH release through nonopiate non-GH-releasing hormone (non-GHRH) receptors. To determine the effects of a 24-h GHRP infusion, eight normal young men received infusions of saline for 2 h, then saline (on two occasions) or GHRP (1.0 micrograms/kg.h; on two occasions) for 24 h, followed by an iv bolus of GHRP or GHRH (1.0 micrograms/kg) and a 2.5-h saline infusion. Serum GH was measured every 10 min throughout the 28.5-h period. GH secretion rates [per L distribution volume (Lv)] were determined by deconvolution analysis; attributes of pulsatile GH release were assessed by Cluster analysis. GH secretion was enhanced and remained pulsatile during GHRP infusions. The two GHRP infusions increased GH secretion rates (micrograms per Lv/h) 8-fold compared to saline (GHRP, 12 +/- 2.1 and 12 +/- 2.2; saline, 1.5 +/- 0.34 and 1.4 +/- 0.27; P < 0.05). The number of GH pulses, pulse duration and height, incremental pulse amplitude, interpeak valley concentration, and individual pulse areas were significantly greater during GHRP infusions than during saline treatment. Attributes of pulsatile GH release on the two GHRP infusion days were significantly correlated, indicating that enhancement of GH secretion by GHRP is highly reproducible. Mean plasma insulin-like growth factor-I (IGF-I) concentrations increased 12% and 22% on GHRP infusion days, whereas IGF-I levels declined 18% and 20% during saline infusions (P < 0.05). GHRP infusion significantly attenuated the GH response to a subsequent GHRP bolus injection; both GH secretion rates (GHRP, 4.1 +/- 1.6; saline, 19 +/- 3.0 micrograms/Lv.h; P < 0.05) and peak GH concentrations (GHRP, 7.9 +/- 2.9; saline, 25 +/- 2.9 micrograms/L; P < 0.05) were decreased. In contrast, peak GH concentrations in response to GHRH were significantly increased after GHRP infusion compared to those after saline treatment (24 +/- 4.7 vs. 11 +/- 2.7 micrograms/L; P < 0.05). We conclude that 24-h GHRP infusions augment pulsatile GH release and increase plasma IGF-I concentrations without significant adverse effects. Attenuation of the GH response to a subsequent GHRP bolus is not caused by depletion of pituitary GH, since the response to a GHRH bolus was enhanced by prior infusion of GHRP. PMID- 8496312 TI - Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-B metabolism in hypothyroidism. AB - T4 replacement at 150 micrograms/day in a group of six hypothyroid subjects led to the development of a euthyroid state and produced a fall in the cholesterol content of plasma and low and high density lipoproteins (LDL and HDL). The effect of T4 on apolipoprotein-B (apoB) metabolism was followed using radioiodinated very low density lipoprotein1 (VLDL1; 60-400 Svedberg units) and VLDL2 (20-60 Svedberg units). The pretreatment plasma concentration of VLDL1 apoB and its rates of synthesis and catabolism were similar to those in normal subjects. VLDL2 apoB was synthesized at a supranormal rate in hypothyroid subjects, and this led to a doubling of its circulating mass. Treatment did not significantly alter the kinetics of apoB in either VLDL1 or VLDL2. The concentration of intermediate density lipoprotein (IDL) apoB in untreated hypothyroids was 170% of normal and fell during T4 treatment due to stimulation of conversion of LDL (from 0.46 +/- 0.14 to 0.91 +/- 0.30 pools/day; mean +/- SD; P < 0.01). Direct IDL apoB clearance was not altered by treatment, whereas the fractional catabolic rate of LDL increased 76% (from 0.17 +/- 0.06 to 0.27 +/- 0.07 pools/day), leading to a 36% decrement in LDL mass. The stimulation of IDL to LDL conversion during therapy was probably due to a 3-fold increase in hepatic lipase activity (P < 0.02). This change together with the known effects of T4 on LDL receptors largely explained the lipoprotein abnormality in hypothyroidism and the effects of replacement therapy. PMID- 8496313 TI - An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial. AB - The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8496314 TI - Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. AB - The GH1 genes of probands of two families with familial isolated GH deficiency (IGHD) were sequenced. Double stranded sequencing of the polymerase chain reaction (PCR) amplification products from genomic DNA of two affected cousins in a consanguineous Turkish family revealed a G-->A transition in the 20th codon of the GH1 signal peptide. This substitution converts a TGG (Trp) to a TAG (stop) codon and generates a new AluI recognition site. PCR amplification of the GH1 alleles of family members, followed by AluI digestion, revealed that the G-->A transition segregated with the IGHD phenotype. In a Saudi Arabian family, a G-->C transversion was found that alters the first base of the donor splice site of intron IV. This substitution should perturb mRNA splicing, resulting in an altered protein product which should be unstable or bioinactive. This transversion also destroys an HphI site, which was used to assay samples from relatives. Digestion of PCR amplification products with HphI demonstrated cosegregation of the G-->C transversion with IGHD. These results demonstrate that familial IGHD is a heterogeneous disease that perturbs different steps in the expression of the GH1 gene. PMID- 8496315 TI - Glucose metabolism and leg blood flow after pancreas/kidney transplantation. AB - Patients with insulin-dependent diabetes mellitus (IDDM) who have undergone combined pancreas and kidney (P/K) transplantation, are hyperinsulinemic and have impaired insulin-stimulated whole body glucose uptake. We have investigated whether their reduced glucose uptake was due to insulin resistance at the tissue level or was caused by reduced muscle blood flow, previously reported to be present in patients with IDDM. Leg blood flow (LBF, determined with mercury strain-gauge plethysmography), glucose uptake (GRd, determined with 6,6 D2 glucose), and glucose oxidation (Gox, determined by indirect calorimetry) were obtained during euglycemic-hyperinsulinemic (approximately 500 pM) clamping in five P/K patients, five kidney transplant (K) patients, and six controls. Insulin stimulated GRd was reduced in P/K patients compared to controls (23 +/- 4 vs. 44 +/- 6 mumol/kg/min, P < 0.05); Gox was comparable but glucose storage was reduced in P/K and K patients compared to controls (9 +/- 3 and 13 +/- 4 vs. 28 +/- 7 mumol/kg/min, P < 0.05). Basal LBF (3.9 +/- 0.3, 4.6 +/- 0.9, and 4.9 +/- 0.6 mL/dL leg tissue/min) and insulin-stimulated LBF (5.6 +/- 0.6, 6.1 +/- 1.1 and 6.1 +/- 0.9 mL/dL leg tissue/min) were similar in P/K, K patients, and controls. We concluded, that P/K patients had normal muscle blood flow but were insulin resistant at the tissue level, and that the insulin resistance was responsible, at least in part, for their hyperinsulinemia. PMID- 8496316 TI - Defects in beta-cell function in functional ovarian hyperandrogenism. AB - Previous studies have shown that hyperinsulinism is associated with hyperandrogenism in patients with the polycystic ovary syndrome, a form of functional ovarian hyperandrogenism (FOH). Although many studies have documented insulin resistance and hyperinsulinemia in polycystic ovary syndrome, the relative roles of insulin secretion and clearance in the pathogenesis of the hyperinsulinism remain uncertain. In this study, using individually derived C peptide kinetic parameters, insulin secretion rates were calculated directly from plasma C-peptide concentrations in 10 patients with FOH and 7 weight-matched control subjects. All subjects were studied during a 24-h period when they ate a standardized diet consisting of 3 mixed meals. On a separate occasion, insulin sensitivity was calculated during a hyperinsulinemic euglycemic clamp. Although glucose concentrations in both groups were within the normal range, the FOH group had higher basal (P < 0.01) and 24-h insulin (P < 0.04) concentrations. The increased insulin concentrations reflected both a reduced clearance (P < 0.02) and an increased secretion of insulin. Basal insulin secretion rates were significantly increased (P < 0.04) in the FOH patients. By contrast, their incremental insulin secretory response to meals was markedly reduced. This reduction in the postprandial responses resulted from a reduction in the relative amplitude of meal-related (P < 0.007) secretory pulses, rather than from a reduction in the number of pulses present. Insulin sensitivity was also lower in those with FOH. Thus, women with FOH have significantly higher basal insulin secretory rates and attenuated secretory responses to meals. These secretory patterns resemble those of noninsulin-dependent diabetes mellitus more than they do those of simple obesity. PMID- 8496317 TI - Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. AB - The condition termed 46,XY complete gonadal dysgenesis is characterized by the lack of testicular determination with resulting streak gonads, normal Mullerian structures, and female external genitalia. In the partial form, there is incomplete testicular determination with a wide range in the degree of ambiguous genitalia and sexual duct development. We evaluated a kindred in which a partial form of 46,XY gonadal dysgenesis occurred in four subjects from two generations. Pedigree analysis indicated an X-linked or possibly an autosomal sex-limited mode of inheritance. All affected subjects were ascertained because of ambiguous genitalia with minimal virilization. At 10 days of age, the proband had a subnormal plasma level of testosterone, and at 4 months, there was no rise in plasma T after stimulation with hCG. At laparotomy, a dysgenetic gonad was found on the right side, but no gonad was found on the left side. A vas deferens was present on the right, indicating the presence of functional Leydig cells early in fetal life. In the other affected subjects, gonadal tissue was also limited to one side of the abdomen and showed poorly developed seminiferous tubules. The sex determining region Y gene, which encodes the testis-determining factor, was present and unaltered in the genomic DNA of all affected subjects. Duplication of the distal short arm of the X-chromosome has been associated with 46,XY complete gonadal dysgenesis in some patients. In our studies, Southern blot analysis revealed that sequences of the distal short arm of the X-chromosome (DXS9 to DXS84) were present in single copy, excluding a large duplication in this area of the X. Several kindreds with familial 46,XY complete gonadal dysgenesis have been reported; five of them had evidence of an X-linked mode of inheritance. Our study of a kindred with 46,XY partial gonadal dysgenesis further supports the role of an X chromosome gene in testicular determination. Evidence of some fetal Leydig cell function in the affected subjects of our report suggests that mutations of the putative X-chromosome gene can result in a partial as well as complete defect in testicular determination. PMID- 8496318 TI - Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta. AB - Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone. PMID- 8496319 TI - High expression of cytochrome b5 in adrenocortical adenomas from patients with Cushing's syndrome associated with high secretion of adrenal androgens. AB - The mechanism of dissociated secretion between adrenal androgens and cortisol observed in several clinical situations remains unclear. We investigated whether the electron transfer systems NADPH-cytochrome P450 reductase and cytochrome b5, both of which had been shown to increase 17,20-lyase activity in vitro, were involved in the reaction selectivity between 17 alpha-hydroxylase and 17,20-lyase in adrenocortical adenomas obtained from eight patients with Cushing's syndrome producing different concentrations of adrenal androgen. In vitro enzyme assay using microsomal fraction of adenoma indicated that all adenomas from seven patients showed almost the same degree of 17 alpha-hydroxylase and 3 beta hydroxysteroid dehydrogenase (3 beta HSD) activities. However, the 17,20-lyase activities of two adenomas producing high concentrations of adrenal androgens were 3-fold greater than those of other five adenomas producing low concentrations of adrenal androgens. The mRNA concentrations of cytochrome P45017 alpha and 3 beta HSD were approximately the same in all adenomas, whereas those of cytochrome b5 in two adenomas possessing high 17,20-lyase activities were greater than those in other adenomas. The increased levels of cytochrome b5 in the two adenomas were further confirmed at the protein level using Western blot analysis of the microsomal fraction. No significant expression of NADPH cytochrome P450 reductase was detected in any of the adenomas by Northern blot analysis. These results suggest that the difference in the concentration of cytochrome b5 in adrenal adenomas from patients with Cushing's syndrome may partially account for the difference in the amount of adrenal androgens produced by the tumors. PMID- 8496320 TI - Growth hormone-binding protein determination in plasma: a comparison of immunofunctional and growth hormone-binding assays. AB - The recent development of an immunofunctional assay for GH-binding protein (GHBP) facilitates measurement of GHBP in biological fluids. Previous methods employed GH binding followed by size exclusion chromatography to determine GHBP levels (GH binding assay), and a considerable body of information exists based on data obtained with that type of assay. To cross-validate the two methods and permit comparison of results obtained in the two assays, we measured GHBP by both methods in 61 plasma samples from normal adults (aged 19-69), 10 patients with acromegaly, 2 patients with Laron dwarfism, and in a normal adult plasma pool. The results show a good overall correlation between the two methods (r = 0.669). However, for individual observations, the coefficient of determination was not high enough to permit interconversion of data with high precision. There is both biological and methodological variation in GHBP levels, rendering the interpretation of a single observation difficult except in the extreme range. The range of values was wider in the immunoassay (56-1187 pmol/L) than in the GH binding assay (12.1-36.1% GH bound/400 microL). There was no significant sex difference in plasma GHBP levels, nor was there an age-dependent trend in adult subjects as assessed by both assays. Patients with acromegaly had significantly decreased GHBP levels in both assays, but the majority of the values were within the low normal range. The two patients with Laron dwarfism had undetectable GHBP in both assays. The previously defined unit of GHBP (i.e. the amount contained in 1 ml pooled adult plasma) corresponds to 256 fmol GHBP as determined by immunofunctional assay. PMID- 8496321 TI - Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins. AB - Evidence has suggested that dehydroepiandrosterone sulfate (DS) is a prehormone for ovarian steroidogenesis. To study this hypothesis, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C]testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery, and the data were compared to those from nine normal women. The concentrations of tracer and nonisotopic DS, androst-5-ene-3 beta,17 beta diol sulfate (delta 5diolS), androst-5-ene-3 beta,17 beta-diol (delta 5diol), dehydroepiandrosterone (D), androstenedione (delta 4A), and T were determined in arterial and venous blood and in follicular fluid. From these data, the concentrations and fractions of steroids in the follicular fluid that were derived from DS were calculated from the specific activity of intravascular DS and the concentrations of follicular fluid tracer steroids and their specific activities. The fractions of T (0.48), delta 5diol (0.31), delta 5diolS (0.42), and D (0.25) in follicular fluid arising from circulating DS were similar and were not significantly different from that of follicular DS arising from circulating DS (0.32). However, the fraction of follicular fluid delta 4A (0.041) was significantly less (P < 0.01), and the fractions of intrafollicular estrone and estradiol arising from DS were both less than 0.04. The mean MCR of DS in the women treated with menotropins of 22.0 +/- 3.5 L/day (mean +/- SE) was significantly higher than the normal control value. These findings elucidate an important mechanism of adrenal/ovarian interaction at the level of steroidogenesis; circulating DS serves as a prehormone for the production of intrafollicular delta 5diolS, delta 5 diol, D, and T. PMID- 8496322 TI - Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors. AB - Uterine leiomyomas, which are myometrial smooth muscle tumors, secrete PRL. We investigated the actions of several hormones known to stimulate PRL secretion by the pituitary gland or decidua on PRL secretion by leiomyoma-derived smooth muscle cells (SMC) in monolayer culture. Cultures were verified to be SMC by immunostaining for smooth muscle alpha-action and desmin. Hormone treatments were performed in serum-free medium for 72 h. Medium was harvested every 24 h and assayed for PRL. 17 beta-Estradiol, progesterone, TRH, insulin-like growth factor I, epidermal growth factor, and the GnRH agonist leuprolide did not affect PRL secretion by these SMC. Insulin caused a significant suppression of PRL secretion by 72 h, and this was accompanied by a 64% increase in total cell protein per well, which represented an increase in cell number. Cells were also plated at various densities to determine the effects of cell number on PRL secretion. The amount of PRL secreted per 1000 cells decreased significantly as cell number per well increased. Northern blot analysis identified PRL mRNA in fresh leiomyoma tissue. PRL mRNA in three independent cultures of SMC was then detected by reverse transcription and the polymerase chain reaction. Hybridization occurred only with the expected band of approximately 423 basepairs in size. We conclude that leiomyomas express PRL mRNA in vivo and that leiomyoma-derived SMC in culture continue to express the PRL mRNA and secrete PRL in the absence of ovarian steroids. PRL secretion by SMC in culture appears to be modulated primarily by changes in cell density. PMID- 8496323 TI - Human granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro. AB - The presence of mRNA transcripts and/or immunoreactivity for PTH-related protein (PTHrP) in several normal mammalian tissues suggests a possible paracrine or autocrine role for this hormone. Since immunohistochemical studies of human ovary demonstrate the presence PTHrP immunoreactivity in this tissue, we wondered if ovarian follicular fluid (OVFF) might contain PTHrP. We retrospectively analyzed 28 OVFF samples obtained at ova harvest in 21 women undergoing in vitro fertilization. Fourteen samples contained significant adenylate cyclase stimulating activity in a PTHrP-sensitive bioassay. In a subsequent prospective analysis, 41 of 45 freshly obtained OVFF samples demonstrated significant activity. This bioactivity was completely neutralized by antisera to PTHrP, but was unaffected by antisera to PTH. Fifteen OVFF samples were also analyzed in a sensitive 2-site immunoradiometric assay for PTHrP, and all 15 demonstrated significant levels of the hormone. The PTHrP levels did not correlate with the presence of an ovum in the follicle or with follicular fluid calcium. Short term (24- to 48-h) cultures of granulosa-luteal cells established from 5 OVFF samples demonstrated constitutive secretion of PTHrP using the immunoradiometric assay. Neither progesterone nor estrogen affected basal secretion. RNase protection analysis of cellular RNA prepared from cultured granulosa-luteal cells demonstrated the presence of mRNA for PTHrP in these cells. We conclude that 1) human OVFF obtained after stimulation with FSH and LH contain high concentrations of PTHrP; and 2) the granulosa-luteal cell is capable of secreting PTHrP both in vivo and in vitro. PMID- 8496324 TI - Neonatal treatment of male monkeys with a gonadotropin-releasing hormone agonist alters differentiation of central nervous system centers that regulate sexual and skeletal development. AB - Male rhesus monkeys treated continuously with a GnRH agonist for the first 4 months of postnatal life exhibited a delay in the onset of puberty and an attenuated peripubertal rise in testosterone (T) secretion. The objectives of the current study were to determine whether these effects on sexual development were permanent and whether the hypothalamic-pituitary-testicular axis was functioning normally in these animals as adults. Neonatal GnRH agonist treatment delays but does not permanently block sexual maturation in male monkeys. Treated animals that did not show a pubertal rise in serum T during the breeding season of their 4th year exhibited a seasonal but subnormal elevation of serum T during the subsequent breeding season. Growth of the skeleton was diminished as evidenced by shorter adult crown-rump, tibia, and femur length and reduced bone mineral density of the humerus and lumbar spine. The magnitude of the serum LH and T response to iv pulses of GnRH [50 ng/kg body weight (BW)] and naloxone (1 mg/kg BW) did not differ between control and treated animals during the nonbreeding or breeding season at 6 yr of age. Conversely, treated animals showed a subnormal serum LH and T response to N-methyl-D,L-aspartic acid (5 mg/kg BW iv) during the nonbreeding season. These data suggest that adult monkeys treated neonatally with a GnRH agonist exhibit subnormal sensitivity of the central nervous system to one or more excitatory amino acids (e.g. aspartate or glutamate). Thus, abolishing neonatal activation of the pituitary-testicular axis with a GnRH agonist may permanently alter differentiation of central nervous system centers that are either involved in GnRH secretion or govern this process. PMID- 8496325 TI - Is infancy a quiescent period of testicular development? Histological, morphometric, and functional study of the seminiferous tubules of the cebus monkey from birth to the end of puberty. AB - The objective of this study was to describe the maturational changes observed in the seminiferous tubules of the monkey Cebus apella, a New World primate species, from birth to the end of puberty. Nineteen animals were subdivided into four groups: neonatal (1-40 days), infantile (4 months to 1 yr), early pubertal (1 yr, 8 months to 2 yr, 9 months), and late pubertal (4-8 yr). Volumetric determinations of different testicular components were made, tubule diameter and length were calculated, and spermatogenic cells, Sertoli cells, and androgen binding protein secretion were quantified. Testicular and seminiferous tubule volumes increased significantly in the first 5 months of life and during puberty due to the combined increment in seminiferous tubule diameter and length. The total number of spermatogonia increased until late puberty to stabilize subsequently. Spermatocytes and spermatids appeared during puberty and increased dramatically until the end of this period. The germ cell ratios, indicative of spermatogenic efficiency, improved continuously in late puberty coincidentally with a reduction of spermatocyte degeneration. Sertoli cells proliferated in the neonatal and infantile periods, determining a longitudinal growth of the seminiferous tubules, but remained stable during puberty, when androgen-binding protein secretion increased significantly. The multiplication of germ cells is the main factor responsible for the increment in tubule diameter during puberty and determines the most noticeable postnatal modification of testicular volume. During late puberty, the reduction of spermatocyte degeneration leads to an increment in germ cell ratios and a progressive, but slow, improvement of spermatogenic efficiency, explaining why pubertal development of the testis occurs over such a prolonged period in this primate. This is in contrast to what happens in most laboratory animals and suggests that the Cebus is a useful model for studies of human male puberty. PMID- 8496326 TI - The accumulation of prostaglandins (PG) in amniotic fluid is an aftereffect of labor and not indicative of a role for PGE2 or PGF2 alpha in the initiation of human parturition. AB - The accumulation of prostaglandins (PGs) in amniotic fluid (AF) during labor is cited frequently as one line of evidence in support of a role for these eicosanoids in the initiation of human parturition. In this study, we evaluated an alternate possibility, viz. that PGs entering AF at parturition are produced as a sequela of labor-associated processes. During labor, the AF normally becomes separated into two compartments, viz. the forebag and the upper compartment, by the obstruction produced as the descending fetal presenting part is engaged in the maternal pelvis. We theorized that the PGs that enter AF are produced in traumatized tissues lining the forebag, which is formed as the result of labor driven cervical dilatation. In addition, these traumatized tissues are exposed to and bathed by the vaginal fluid, which contains many potent stimuli of PG formation, viz. large numbers of microorganisms and bacterial toxins. AF was collected at term before labor (n = 50) and from the upper compartment during labor (n = 47) by transuterine amniocentesis, and AF was collected by direct needle aspiration of the forebag during labor (n = 143). PGF2 alpha, 13,14 dihydro-15-keto-PGF2 alpha (PGFM), and PGE2 were quantified by RIA. The concentrations (nanomoles per L mean +/- SEM) of PGs in AF of the forebag (PGF2 alpha, 85.6 +/- 10.6; PGFM, 20.8 +/- 2.58; PGE2, 26.9 +/- 2.73) were much greater than those in the AF before labor (PGF2 alpha, 0.56 +/- 0.05; PGFM, 0.9 +/- 0.08; PGE2, 5.89 +/- 1.13) or in AF of the upper compartment during labor (PGF2 alpha, 7.14 +/- 1.64; PGFM, 5.11 +/- 0.82; PGE2, 8.74 +/- 1.71). The concentrations of PGs in AF of the upper compartment during early labor (< or = 2.5-cm cervical dilatation) were no greater than those in AF before labor began. The concentration and total content of PGs in AF of the forebag increased as a function of cervical dilatation until delivery. At 3- to 5-cm cervical dilatation, the levels of PGs in AF of the upper compartment were greater than those before labor, but significantly less than those in AF of the forebag at the same stage of labor progress. After 3-5 cm, the levels of PGs in the upper compartment did not increase further. These findings indicate that PGF2 alpha, PGFM, and PGE2, which enter AF in increased amounts during parturition, are produced during, not before, labor in tissues (principally decidua) lining for forebag.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496327 TI - Follicle-stimulating hormone induces dose-dependant stimulation of immunoreactive inhibin secretion during the follicular phase of the human menstrual cycle. AB - To determine whether FSH is a physiological regulator of the serum immunoreactive inhibin (INH) concentration during the follicular phase of the normal menstrual cycle, purified FSH (Metrodin) was administered in doses of 100 IU (n = 6), 150 IU (n = 5), and 200 IU (n = 5) to normal, regularly cycling volunteers between days 3-7 of the menstrual cycle. A control group (n = 5) received normal saline. There was a linear dose-related increase in serum INH (and in serum FSH) in response to the three doses of FSH, with 200 IU leading to a 107% increase in INH and a 68% increase in FSH. Serum estradiol rose in response to the two higher doses of FSH. There was a significant correlation between the actual increases in INH and estradiol (r = 0.53; P < 0.01). It was concluded that FSH stimulates INH in the follicular phase of the normal menstrual cycle, consistent with a physiological role for FSH in the regulation of granulosa cell production of inhibin. PMID- 8496328 TI - Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. AB - The physiological role of GH in the adult skeleton is unknown. In this study, 12 adults (10 males and 2 females) with isolated GH deficiency were treated with GH as a single daily sc injection (0.125 IU/kg.week for the first 4 weeks and subsequently at 0.25 IU/kg.week) for 1 yr in a double blind, placebo-controlled manner. Bone mineral density of the spine (T12-L3) was measured by quantitative computed tomography, and bone mineral content (BMC) of the forearm by single photon absorptiometry at entry into the study and subsequently at 6 monthly intervals. All baseline bone mineral measurements were reduced compared with those in an age- and sex-matched control population. In the treatment cohort, quantitative computed tomography spinal trabecular bone mineral density increased by 7.8 g/L after 6 months of GH replacement (mean +/- SEM, 151.7 +/- 6.0 vs. 159.5 +/- 5.9 g/L; n = 11; P < 0.01), and this increment was maintained at 1 yr (160.7 +/- 6.3 g/L). Proximal forearm (cortical) BMC showed no change after 6 months of GH replacement, but there was a significant increase of 0.06 g/cm after 12 months of GH replacement (from 1.38 +/- 0.04 to 1.44 +/- 0.04 g/cm; n = 12; P < 0.05). Distal forearm (cortical and trabecular) BMC also increased significantly during the study period from 1.46 +/- 0.04 g/cm to 1.52 +/- 0.05 g/cm; n = 12, P < 0.05. No significant changes occurred in bone mineral measurements during 6 months of placebo therapy. Midthigh muscle and fat cross sectional area increased and decreased, respectively, during the active treatment phase. These results demonstrate that GH plays an important role in maintaining the integrity of the adult skeleton. PMID- 8496329 TI - Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease: coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II. AB - Using a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were variable, but displayed a close correlation to the expression of thyroid peroxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), and the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. Overall, TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybridization showed that apart from lymphocytes, thyroid cells themselves were the source of MHC II transcripts. gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that next to lymphocyte infiltration, active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters (TSH-R, thyroid peroxidase, thyroglobulin, and c fos) and immunological markers (MHC I and II). PMID- 8496330 TI - Increased adrenal medullary atrial natriuretic polypeptide synthesis in patients with primary aldosteronism. AB - The present study was designed to determine whether atrial natriuretic polypeptide (ANP) is synthesized in the human adrenal gland and, if so, to investigate the ANP content of adrenal tissue and the ANP mRNA changes in patients with primary aldosteronism. A considerable amount of human alpha ANP like immunoreactive substances was extracted from the remnant adrenal glands of three patients with primary aldosteronism (1.44, 1.0, and 0.77 pmol/g wet tissue; mean +/- SD, 1.07 +/- 0.28 pmol/g) and the adrenal glands of three kidney donors for transplantation (0.93, 0.58, and 0.27 pmol/g wet tissue; mean +/- SD, 0.59 +/ 0.27 pmol/g). High performance gel permeation chromatographic analysis coupled with a RIA of the tissue extract showed that the molecular form of ANP in the adrenal gland was the precursor form, i.e. human gamma ANP. An in situ hybridization study using an ANP cRNA probe indicated that the ANP mRNA was localized mainly in the medullary area of the gland. Northern blot analysis, using ANP cDNA as a probe, detected ANP mRNA in the adrenal gland. Furthermore, the level of ANP mRNA in the adrenal glands of patients with primary aldosteronism was obviously elevated compared to that in the kidney donors. Our results were the first to indicate that ANP is synthesized in the human adrenal medulla, and such medullary ANP synthesis increases in patients with hypermineralocorticoidism. These facts support the proposal that extraatrial (medullary) ANP synthesis might act in a paracrine or endocrine manner to regulate water and electrolyte homeostasis. PMID- 8496331 TI - New technique for quantitation of pituitary adenoma size: use in evaluating treatment of gonadotroph adenomas with a gonadotropin-releasing hormone antagonist. AB - Because administration for 1 week of the GnRH antagonist Nal-Glu GnRH had been shown to decrease FSH secretion from supranormal to normal in men with gonadotroph adenomas, we investigated the effect of prolonged administration of Nal-Glu on the size of gonadotroph adenomas. To quantitate the effect of Nal-Glu GnRH on gonadotroph adenoma size, we first developed a technique for calculating adenoma volume. The technique involved collecting magnetic resonance (MR) imaging data from each adenoma at 1-mm slice intervals in the coronal, axial, and sagittal views and using the Softvu computer program to calculate adenoma volume from the MR data. The precision of this technique, as judged by the coefficients of variation of the calculations of the same view of the same study three times, was 1.7%, 1.0%, and 1.0% for each of three studies. When Nal-Glu GnRH (5 mg, sc, every 12 h) was self-administered for 3-12 months to five men with gonadotroph adenomas and supra-normal serum FSH concentrations, the serum FSH concentrations decreased to normal or below normal for the entire treatment period. Adenoma size, however, did not change during treatment in any of the five men. We conclude that calculating pituitary adenoma volume from MR data using the Softvu computer program is a highly reproducible technique, but that Nal-Glu GnRH is not an effective treatment for reducing gonadotroph adenoma size. The failure of Nal Glu to reduce adenoma size despite its success in reducing FSH secretion suggests that FSH secretion from gonadotroph adenomas is dependent on endogenous GnRH, but growth of gonadotroph adenomas is not. PMID- 8496332 TI - Modulation of the steroidogenesis of cultured human granulosa-lutein cells by gonadotropin-releasing hormone analogs. AB - GnRH analogs are widely used in reproductive medicine to create a hypogonadotropic hypogonadism. However, numerous animal studies have demonstrated a direct regulation of the gonadal function by GnRH. To ascertain this direct ovarian effect in humans, the steroidogenesis of cultured human granulosa cells was studied with or without GnRH and five of its agonists. Buserelin (D Ser(But)6, desGly10) GnRH ethylamide, leuprorelin (D-Leu6, desGly10) GnRH ethylamide, H4055 (desGly10) GnRH ethylamide, and H4065 (D-Trp6, desGly10) GnRH ethylamide significantly enhanced estradiol secretion. In addition, buserelin induced a significant cell surface decrease that seemed to be mediated by cytoskeleton modifications. The two other molecules, GnRH and triptorelin (D Trp6) GnRH), had no effect on estrogen secretion at any of the studied concentrations. Thus, despite similar pituitary effects, these agonists did not exhibit the same ovarian action. This may be accounted for by the differences found between pituitary and ovarian receptors. These results suggest that some GnRH analogs can modulate human granulosa cell steroidogenesis at least in the preovulatory period. PMID- 8496333 TI - Physiologic hyperinsulinemia enhances counterregulatory hormone responses to hypoglycemia in IDDM. AB - We evaluated the effect of physiologic hyperinsulinemia (plasma insulin 329 +/- 62 vs 687 +/- 62 pmol/L) on counterregulatory hormone responses in 8 IDDM subjects studied during a 2-hour hypoglycemic clamp study with an equivalent degree of hypoglycemia (plasma glucose 3.1 +/- 0.1 and 3.0 +/- 0.1 mmol/L, respectively). Plasma epinephrine levels were increased by 71% during the last 60 minutes of hypoglycemia in the high insulin study (840 +/- 180 vs 1440 +/- 310 pmol/L, respectively p = 0.006). In addition, plasma cortisol and norepinephrine were also increased in the high insulin study (by 19% and 24% respectively, p < 0.01, for both). Plasma growth hormone and glucagon concentrations were not altered by high dose insulin infusion. In spite of increased epinephrine secretion, the glucose infusion rate required to maintain glucose was 2-fold greater in the high insulin study, and there was greater suppression of lipolysis in that group. We conclude that hyperinsulinemia may enhance counterregulatory hormone secretion in IDDM. PMID- 8496334 TI - Potential agonist action of the interleukin-1 receptor antagonist protein: implications for treatment of women. AB - The interleukin-1 receptor antagonist protein (IRAP) caused a concentration related increase in prostaglandin production by human decidual cells. The degree and time course of this stimulatory action were identical to those induced by interleukin 1 beta (IL-1 beta). IRAP had no inhibitory action on IL-1 beta stimulation of decidual prostaglandin production and at high concentrations had an additive effect. We believe that this represents the first description of a potential agonist action of IRAP and suggests caution in treatment of women with this substance. PMID- 8496335 TI - Molecular detection of interferon-alpha expression in multiple sclerosis brain. AB - The demonstration of intermittent interferonaemia in patients with multiple sclerosis prompted a molecular analysis of brain tissue for expression of interferon-alpha genes. A sensitive method was developed based on the polymerase chain reaction. Primer sets were used that could amplify all interferons-alpha or two particular subtypes, interferon-alpha 2 and interferon-alpha 4. The procedure was successful in detecting expression of interferons-alpha in brain and non brain tissues in most patients with multiple sclerosis. However, expression was demonstrable also in a similar proportion of patients with other neural diseases, and patients with other illnesses. The data indicate that there can be constitutive expression of interferons-alpha in brain tissue, but the possibility that this becomes amplified in multiple sclerosis was not revealed by this study. PMID- 8496336 TI - Suppression of experimental autoimmune encephalomyelitis by restraint stress: sex differences. AB - We have recently reported that female Lewis rats exhibit significantly higher basal circadian levels of corticosterone (Cort) than male Lewis rats. The studies reported here were designed to explore whether male and female Lewis rats demonstrate a differential suppression of experimental autoimmune encephalomyelitis (EAE) following exposure to an identical regimen of repetitive restraint stress. Rats were restrained for 1 or 9 h/day beginning 5 days before myelin basic protein (MBP) challenge and extending through the recovery period (18 days post challenge). Both clinical signs and histopathological changes of EAE were more significantly suppressed in 9-h-stressed females relative to male Lewis rats. Investigation of the mechanism underlying the stress-induced suppression of EAE revealed that restraint stress did not alter the clinical course of EAE in rats challenged with MBP 68-88 encephalitogenic peptide, suggesting that restraint stress may affect processing and/or presentation of the MBP molecule. Stressed rats exhibited decreased interleukin-2 and interferon gamma production, and the frequency of MBP-reactive lymphocytes was reduced in comparison to non-stressed rats. Finally, repetitive restraint stress had no effect on blood-spinal cord permeability during EAE. The results presented here underscore the importance of such experimental variables as sex, strain, time of day, and the kinetics of immune response development. PMID- 8496337 TI - Generation of cellular immune responses against a glioma-associated antigen(s). AB - The study demonstrated that RT2, a highly malignant anaplastic glioma, expresses antigens that make it susceptible to in vivo adoptive immunotherapy with cytotoxic T lymphocyte-containing immune cell populations. Rats were immunized with irradiated RT2 tumor cells and the adjuvant C. parvum. Lymphocytes from immunized rats were restimulated in vitro with irradiated RT2 tumor cells plus interleukin-2 (IL-2). The cells that proliferated and differentiated in vitro effectively killed RT2, but only low levels of cytotoxicity were observed against other histopathologically related and unrelated, syngeneic and allogeneic target cells. Adoptive transfer of immune cells combined with a 5-day course of systemic IL-2 produced specific regression of brain tumors growing as lung microfoci. PMID- 8496338 TI - Inescapable footshock exposure differentially alters antigen- and mitogen stimulated spleen cell proliferation in rats. AB - A variety of stressors have been shown to influence specific and non-specific measures of immune function in laboratory animals. One of the most common tools used to evaluate lymphocyte function is the non-specific mitogen proliferation assay. Assessment of this function in the rat spleen has revealed profound suppression following restraint, electric shock, and re-exposure of animals to a fearful context. However, there have been no studies that have compared the effects of stressor exposure on mitogen- and specific antigen-stimulated spleen cell proliferation. Therefore, the present study addressed this issue through experiments in which rats were immunized intraperitoneally with 1 microgram cholera toxin and exposed to acute (one session) or repeated (three consecutive daily sessions) footshock. The results showed that footshock exposure prior to immunization inhibited cholera toxin stimulated spleen cell proliferation 7 days after immunization. Acute or repeated footshock exposure 5-7 days after cholera toxin immunization depressed non-specific spleen cell proliferation, while augmenting the proliferative response to specific antigen. From these observations it can be hypothesized that footshock exposure either differentially regulates lymphocyte activation by clonal and polyclonal signals, and/or naive and memory cells react differently to stressor exposure. PMID- 8496339 TI - Biosynthesis of corticotropin-releasing hormone in human T-lymphocytes. AB - Corticotropin-releasing hormone (CRH) is a 41-amino acid neuropeptide which increases the transcription of the proopiomelanocortin (POMC) gene, as well as the biosynthesis and secretion of POMC-derived peptides. Using a specific human CRH radioimmunoassay we have shown that human T-lymphocytes contain immunoreactive CRH. We studied the effects of phytohemagglutinin (PHA) and 12-O tetradecanoylphorbol-13-acetate (TPA) on the biosynthesis of CRH in human T lymphocyte cell cultures. A significant increase in CRH mRNA levels was observed in human lymphocytes after 12 h of PHA/TPA treatment, while the levels decreased after 22 h. These findings could imply an immunomodulatory role for CRH that could be due to autocrine and/or paracrine interactions. PMID- 8496340 TI - Immunoglobulin heavy chain variable region polymorphisms and multiple sclerosis susceptibility. AB - In addition to the major histocompatibility complex (MHC), genetic susceptibility in multiple sclerosis (MS) appears to be influenced by other loci. A recent study has identified a population association with an immunoglobulin heavy chain variable region polymorphism in the VH2-B5 family, with both familial and sporadic MS patients. We have repeated this association study in a second MS patient group and used two ethnically and geographically matched control groups and the MS patients' unaffected sibs for comparisons. The VH2-B5 polymorphism was found to be over-represented in MS patients when compared to all three control groups. This VH2-B5 association was stronger when the MS patient data were combined with data from our previous study. To further explore the implications of this population association, MS sibships were analyzed for haplotype sharing by identity by descent (IBD) for VH2 and VH3f gene segment polymorphisms. The distribution of haplotype sharing did not differ from that expected based upon random segregation. The data are consistent with the IGVH locus exerting a minor effect perhaps by interacting with other loci to influence MS susceptibility or with genetic heterogeneity and a role for this complex in a subgroup of patients. PMID- 8496341 TI - Enhanced response to antigen within lymph nodes of SJL/J mice that were protected against experimental allergic encephalomyelitis by T cell vaccination. AB - The effects of T cell vaccination on peripheral immune responsiveness are not yet fully understood. We have induced resistance to rat spinal cord homogenate (RSCH) induced experimental allergic encephalomyelitis (EAE) in SJL/J mice by vaccination with four T cell lines (RZ8, RZ15, RZ16, and A51) which were reactive to myelin basic protein (MBP) but not to proteolipid protein (PLP). The effect was relatively neuroantigen-specific since vaccination with ovalbumin (OVA) reactive and alloantigen-specific cells did not prevent EAE induction. Alloantigen-reactive cells reduced the rate of relapse. The number of central nervous system (CNS) infiltrates and mean clinical EAE scores were significantly reduced. This is the first report demonstrating T cell vaccination in the SJL/J mouse, a strain in which PLP is the predominant encephalitogen in RSCH. The vaccinating cells were of the memory/effector (CD44high, CD45RBlow) surface phenotype. We examined the effect of T cell vaccination on lymph node T cell proliferative responses to MBP, encephalitogenic peptides of PLP and MBP, OVA and anti-CD3. With the exception of polyclonal cytokine responses to anti-CD3, which remained unchanged, vaccination led to a 5-10-fold augmentation in all, including background, responses. By comparison with lymph node cell (LNC) responses from naive mice and mice primed with OVA, it appeared that T cell vaccination restored cellular activation levels which had been depleted in peripheral lymphoid tissues of unvaccinated animals with EAE. PMID- 8496343 TI - Why won't they? PMID- 8496342 TI - Fluoride release from orthodontic elastic chain. PMID- 8496344 TI - The claspring: an adjunct to removable appliance therapy. PMID- 8496345 TI - Securing bands to an alginate impression. PMID- 8496346 TI - Shear bond strengths and effects on enamel of two ceramic brackets. PMID- 8496347 TI - Modified mandibular Schwarz appliance. PMID- 8496348 TI - Gnathological orientation splint for presurgical orthodontics. PMID- 8496349 TI - The dilemma of practice transition. PMID- 8496350 TI - Concepts to live by. PMID- 8496351 TI - Nickel titanium palatal expander. PMID- 8496352 TI - Safety catch for a Kloehn facebow. PMID- 8496353 TI - Termination of treatment in cases of non-payment. PMID- 8496354 TI - Single lower incisor extractions. PMID- 8496355 TI - Correction of individual tooth rotations with elastomeric ligatures. PMID- 8496356 TI - Indirect bonding with adhesive precoated brackets. PMID- 8496357 TI - A prospective study of nonoperative and operative management for Perthes' disease. AB - Two groups of children with Perthes' disease, randomized according to their source of referral, were treated by bed rest and skin traction, followed by either use of a weight-relieving caliper or a proximal femoral varus osteotomy. The outcome was similar in both groups and could be predicted more effectively by the arthrographic shape of the femoral head at presentation than by the Catterall grouping. The principal influences were the age of the child when treated and the sphericity of the femoral head. Walking speed at time of review was related to the height of the child and, at this age, was not affected by the shape of the healed femoral head. PMID- 8496358 TI - Anterior impingement of the femoral head: a late phenomenon of Legg-Calve Perthes' disease. AB - A previously unrecognized late phenomenon of anterior impingement of the femoral head in Legg-Calve-Perthes' disease is reported in four patients. After an asymptomatic period following reossification of the femoral head, the patients had pain triggered by internal rotation of their hips. Standard roentgenograms did not indicate any cause of the pain. Computed tomography (CT), arthrography, and arthroscopy demonstrated impingement of the anterior aspect of the femoral head against the anterior rim of the acetabulum on internal rotation of the leg. Three hips had femoral head articular surface damage with osteochondral projections at the area of anterior impingement. Arthroscopic debridement and proximal femoral osteotomy was successful in relieving the symptoms. PMID- 8496359 TI - Narrow window of bone age in children with slipped capital femoral epiphyses. AB - Pelvis radiographs of 30 children with slipped capital femoral epiphyses (SCFE) were reviewed by four readers to determine the skeletal age. The average chronologic age for girls was 12.1 +/- 1.0 years and that for boys was 14.4 +/- 1.3 years; the average pelvic bone age was 13.2 +/- 0.6 for girls and 15.1 +/- 0.6 years for boys. The chronologic age range was 98 months, and skeletal age range was only 50 months. Pelvis bone age was advanced in the youngest children, normal in most children, and mildly delayed in older children. We conclude that there is a uniform skeletal age or "narrow window" during which epiphyseal slipping occurs, regardless of the child's chronologic age. PMID- 8496360 TI - Treatment of moderate to severe slipped capital femoral epiphysis with extracapsular base-of-neck osteotomy. AB - Extracapsular base of femoral neck osteotomy was performed in 36 hips with moderate to severe slipped capital femoral epiphysis (SCFE). Follow-up ranged from 2 to 24 years (average 9 years). According to modified Southwick's criteria, 90% of the hips had excellent or good result. There were no cases of avascular necrosis (AVN). Prevention of permanent limb-length discrepancy > 15 mm, as occurs in unilateral cases, warrants close follow-up and contralateral epiphysiodesis when necessary. We highly recommend this osteotomy as a safe and effective way to prevent further slippage and improve hip range of motion (ROM) in severe chronic slips. PMID- 8496361 TI - Prediction for prognosis from radiologic measurements of patients treated with the Pavlik harness for congenital dislocation of the hip. AB - Radiologic measurement was made in 96 hips of 96 female patients with congenital dislocation of the hip (CDH) treated only with the Pavlik harness before reaching age 6 months until time of maturity. Radiographs were retrospectively examined to determine whether prognosis of the hip joints was predictable up to approximately 3 years of age. Highly accurate prediction was possible using multivariate analysis. The patient group assessed as "satisfactory" with discriminant analysis had an incidence of Severin's classification of group III or lower of < 1% of significance level. This analysis appears to be a useful screening method for judging CDH after treatment. PMID- 8496362 TI - Pavlik harness versus Frejka splint in treatment of developmental dysplasia of the hip: bicenter study. AB - A bicenter study was conducted to compare the results of treatment in developmental dysplasia of the hip (DDH) with Frejka splint versus Pavlik harness. Eighty-four dislocated hips were treated by the Frejka splint, and 48 dislocated hips were treated by the Pavlik harness. Failure of reduction was 10% with the Frejka splint and 12% with the Pavlik harness. Avascular necrosis (AVN, mostly type 1) was detected in 7% of Frejka patients versus 6% in Pavlik patients. The Frejka splint is simpler to use and if properly applied may be as safe as the Pavlik harness for DDH treatment. PMID- 8496363 TI - Magnetic resonance imaging study of acetabular morphology in developmental dysplasia of the hip. AB - Acetabular morphology in developmental dysplasia of the hip (DDH) can be delineated by magnetic resonance imaging (MRI) more accurately than by previously available imaging methods. We describe the acetabular morphology observed in 10 girls and one boy aged < 3 years with untreated DDH. The bony pathology was iliac bone widening with lateral drift of the superior and posterior portions of the acetabular floor (extrusio acetabulae), loss of sphericity, and diminished aperture of the acetabulum. The cartilage changes were a distortion and overgrowth of the acetabular cartilage, including labrum, and a convex appearance of the posterior portion of the acetabular cartilage. PMID- 8496364 TI - No relation between general laxity and atlantoaxial instability in children with Down syndrome. AB - Atlantoaxial instability in children with Down syndrome (DS) may be caused by laxity of the transverse ligament. We tested the hypothesis that general laxity might predict atlantoaxial instability. General laxity and the atlantoaxial distance were assessed in 172 children with DS (aged 6-17 years; 45% girls, 55% boys). No significant correlation was noted between these two measures with either univariate or multivariate methods of statistical analysis. PMID- 8496366 TI - Rectus femoris surgery in children with cerebral palsy. Part I: The effect of rectus femoris transfer location on knee motion. AB - Rectus femoris transfer was performed in 78 children (105 sides) with cerebral palsy (CP) at the same time as other surgical procedures as appropriate. The transfer was either medial to the sartorius (62 sides), semitendinosus (19 sides), or the gracilis (14 sides) muscles, or laterally to the iliotibial band (10 sides). Gait analysis performed before and 1 year after operation demonstrated increased knee range of motion (ROM) with increased extension at initial contact and in midstance and maintained knee flexion in swing. There were no statistically significant differences between the four transfer sites in the effect on those variables. Therefore, the choice of rectus femoris transfer site can be dictated by surgical preference or by the nature of other simultaneous procedures. There was no consistent change in transverse plane motion of the hip or foot progression angles between the two gait analyses, suggesting that rectus femoris transfer does not affect gait abnormalities observed in the transverse plane. PMID- 8496365 TI - Hanging head sign as a presenting feature of spinal cord neoplasms: a report of four cases. AB - A series of four patients presented with a common but unique finding: inability to hold the head in an upright position. Each complained of pain with attempts at passive extension of the neck. All subsequently were diagnosed with spinal cord neoplasms. The literature indicates that the more classic symptoms of spinal cord tumors are often slow to develop and exist for months before being accurately diagnosed. The "hanging head sign" may provide an earlier diagnosis of spinal cord lesions. PMID- 8496367 TI - Rectus femoris surgery in children with cerebral palsy. Part II: A comparison between the effect of transfer and release of the distal rectus femoris on knee motion. AB - Rectus femoris muscle (RF) surgery was performed in 98 children (136 sides) with cerebral palsy (CP). RF transfer was performed in 105 lower limbs, and distal RF release was performed in 31. Eleven (20 sides) similarly affected children had no RF procedure and are included for comparison. Gait analysis was performed just before and approximately 1 year after surgery. All children underwent other orthopaedic surgery at the time of the RF procedure. When preoperative knee range of motion (ROM) was > 80% of normal, there were no significant changes in knee motion in either the RF transfer or distal release groups. In patients with < 80% of normal knee ROM preoperatively, RF transfer was followed by maintained knee flexion in swing; patients who underwent distal RF release or no RF procedure showed a decrease (10 degrees and 6 degrees, respectively) in knee flexion postoperatively. These results suggest that the RF should be transferred and not released when knee ROM is < 80%. PMID- 8496368 TI - Prolongation of ambulation in children with Duchenne muscular dystrophy by subcutaneous lower limb tenotomy. AB - To assess the effect of subcutaneous (s.c.) lower limb tenotomies on the ambulatory ability of patients with Duchenne muscular dystrophy (DMD), 54 patients were followed. Twenty-nine patients underwent hip, knee, and ankle tenotomies at a mean age of 10 2/12 years and were followed postoperatively for an average of 3 9/12 years. These children continued ambulation in long-leg braces to a mean age of 12 8/12 years and stood to an average of 13 5/12 years. Contracture correction was 49% at the hip, 58% at the knee, and 100% at the ankle. A separate group of 25 children to whom operation was offered but declined, was followed: these children ceased ambulating at a mean age of 10 years and ceased standing at a mean age of 10 2/12 years. Thus, we propose that s.c. tenotomy is effective in allowing braced ambulation well beyond what the natural history would allow. PMID- 8496369 TI - Use of the reciprocating gait orthosis in myelodysplasia. AB - There are advantages to an upright posture and ambulation in pediatric myelodysplasia patients. The reciprocating gait orthosis (RGO) is a useful tool to enable this activity in selected individuals. We evaluated the long-term usage, pitfalls, and contraindications of this orthosis. Mean daily usage was 6.9 h/day, requiring an average of 10 min to don or doff; all patients required assistance. Obesity, advanced age, lack of patient or family motivation, scoliosis, and spasticity were significant negative factors in long-term usage of the RGO. Good upper extremity strength, trunk balance, previous standing or walking, and active hip flexion were important positive variables. Eleven of 21 patients did not persist with long-term usage of this orthosis, averaging 25.8 months of usage. An energy study was performed on three patients, comparing the efficiency of reciprocating gait and swing-through gait. All three were more energy efficient and two were faster with the swing-through gait but each preferred the reciprocating pattern. Care should be taken when selecting patients for RGO usage because not all children with myelomeningocele are able to function effectively with this orthosis. PMID- 8496370 TI - Biodegradable fixation of physeal fractures in goat distal femur. AB - We compared the effectiveness of absorbable polylactic acid (PLA) screws and polydioxanone (PDS) pins with that of ASIF cannulated screws in stabilizing Salter-Harris IV fractures in goat distal femur. Eighteen juvenile goats were randomly divided into control (cannulated screw), PLA screw, and PDS pin groups. A Salter-Harris IV medial femoral condyle fracture was created and stabilized, and the goats were sacrificed 8 weeks postoperatively. Articular cartilage displacement < 1 mm was considered anatomic. All PLA screws were anatomic as compared with 83% (five of six) of the controls and 17% (one of six) of the pins. Absorbable PLA screws stabilized Salter-Harris IV fractures as well as cannulated screws and better than PDS pins. PMID- 8496371 TI - Reduction and fixation of displaced radial neck fractures by closed intramedullary pinning. AB - Radial neck fractures in children are serious injuries with frequent sequelae when the tilt exceeds 60 degrees. Conservative treatment is often inadequate in such cases and open reduction may produce iatrogenic complications. We report our experience with an original technique. An intramedullary wire introduced from below and projected upward allows reduction of the displacement and maintenance of the correction without infringing the joint. The operative technique is described. This method was used in 31 fractures with between 30 degrees and 80 degrees of tilt and in 16 fractures with > 80 degrees of tilt. Excellent and good functional results were obtained in 30 cases in the first group and in 11 cases in the second group. PMID- 8496372 TI - Long-term follow-up of anterior tibial eminence fractures. AB - Most children who have sustained a tibial eminence fracture have objective evidence of anterior cruciate ligament (ACL) laxity at long-term follow-up, but few have subjective complaints. Clinical signs of anterior instability were noted in 64% of patients (32 of 50) examined at an average follow-up of 4 years. Objective evidence of laxity determined with a KT-1000 arthrometer was noted in 74% of patients (37 of 50). Five patients (10%) complained of pain, but no patient complained of instability at follow-up. Assessment of long-term stability showed that the method of management (open vs. closed methods) had no bearing on eventual outcome. PMID- 8496373 TI - Effects of splitting the iliac apophysis on subsequent growth of the ilium: a rabbit study. AB - We wished to determine if splitting the iliac apophysis in a skeletally immature animal would affect subsequent growth of the ilium. Thirty-two rabbits were divided into six groups. One group was the sham group; the other five groups received different types of surgical splitting and repair of the iliac apophysis. The results suggested that any splitting of the iliac apophysis in an immature animal significantly affects subsequent growth of the ilium. The type of repair apparently does not affect the amount of growth retardation. Using electrocautery to split the iliac apophysis has a significantly greater effect on growth of the ilium. PMID- 8496374 TI - Management of partial growth arrest: physis, fat, or silastic? AB - A rabbit model was developed for the study of partial growth arrest and its correction by epiphysiolysis and transfer of physis, free fat, or silastic. Growth arrest involved half of the proximal tibial physis. Clinical, radiologic, and histologic studies showed that a physeal graft (from iliac apophysis) was superior to silastic in terms of correction of angular deformity as well as contribution to longitudinal growth of the tibia after resection of a large peripherally situated bone bridge. Interposition of fat yielded the poorest results. PMID- 8496375 TI - Effects of physeal distraction on the vascular supply of the growth area: a microangiographical study in rabbits. AB - To study the effects of physeal distraction on growth plate vascularity, microangiography was performed in 45 growing rabbits. Marked enlargement of the epiphyseal arteries and defective metaphyseal capillary filling were observed in association with hyperplasia and separation of the physes after 3 days of distraction, and the changes still persisted locally in specimens distracted for 21 days. New capillaries were observed in the hyperplastic physes and in separation gaps at 21 days. Vascular anastomoses across the physes were noted after 6 weeks of follow-up. Epiphyseal capillary enlargement may indicate increased nutritional demands of the physis, whereas metaphyseal changes are probably related to separation in the hypertrophic chondrocyte zone. PMID- 8496376 TI - Fibular transfer for congenital absence of the tibia. AB - Twelve patients (13 extremities) who had complete congenital absence of the tibia were treated between 1963 and 1989. Three patients (three extremities) had a knee disarticulation performed as the primary procedure because they had no quadriceps function. Nine patients (10 extremities) underwent centralization of fibula under the femoral condyles (Brown procedure). Four of these 10 extremities developed a severe flexion contracture of the knee (> 25 degrees) and underwent subsequent knee disarticulation. One patient with a short stump secondary to an ipsilateral proximal femoral focal deficiency had a femorofibular arthrodesis. Five of these 10 extremities had a satisfactory result when reviewed at an average follow-up of 18 years. The patients were evaluated in reference to gait, range of motion (ROM) of the knee, quadriceps strength, prosthetic needs, and peer group sports activities. A strong quadriceps (> grade 4) was noted in all five patients who had a satisfactory result. Flexion contracture of the knee, when < 25 degrees, did not compromise the result. PMID- 8496377 TI - Femoral version and neck shaft angle. AB - We measured femoral anteversion by the Kingsley-Olmsted method in 24 unpaired, dry femurs. When the head and neck of the same femurs were measured by computed tomography (CT) scan, measurement was 5 degrees less than the Kingsley-Olmsted method, whereas ultrasound of the head and neck was 5 degrees higher. An anterior flat plane was also defined to help measure anteversion in patients with a high neck shaft angle. Physical and ultrasound measurement correlated well with the previous measurement by the Kingsley-Olmsted method and CT scan of anteversion. Although measurement by CT scan and ultrasound are different their results are both reproducible and measure the same parameters; however, ultrasound measurement yields a number approximately 10 degrees higher. PMID- 8496378 TI - Percutaneous reduction and fixation of displaced juvenile Tillaux fractures: a new surgical technique. AB - Although it is not a very common injury, the juvenile Tillaux fracture is an intraarticular injury, so that accurate reduction is essential to restore the articular surface. Closed percutaneous reduction and internal fixation is a new method of treatment, used when manipulative reduction fails to restore the articular surface. PMID- 8496379 TI - Etiology and pathogenesis of heritable connective tissue diseases. AB - There are many heritable disorders of the connective tissues and many of them produce major musculoskeletal anomalies. The etiology of most of them is unknown, but collagen mutations have been characterized in osteogenesis imperfecta (OI), in some forms of the Ehlers-Danlos syndrome (EDS) and in some of the chondrodysplasias. These diseases, particularly OI, provide a model for investigation of other heritable connective tissue diseases in which the mutant genes have not yet been identified. PMID- 8496380 TI - Ultrasound examination early in evaluation of acute and chronic hip pain in children. PMID- 8496381 TI - Treatment of residual club-foot deformity, the bean-shaped foot--by open wedge medial cuneiform osteotomy and closing wedge cuboid osteotomy, clinical review and cadaver correlations. PMID- 8496382 TI - The white cell differential: personal observations. PMID- 8496383 TI - ACP Broadsheet no 137: April 1993. Obtaining samples at post mortem examination for toxicological and biochemical analyses. PMID- 8496384 TI - Prospective comparative study of computer programs used for management of warfarin. AB - AIMS: To compare the effectiveness of three computerised systems that are currently used for assisting warfarin control in outpatients with the customary dosing method used by experienced medical staff. METHODS: A pilot randomised study of three systems with a follow up independently randomised study of two of these was made on 186 patients receiving long term treatment or who had recently started warfarin treatment and had been discharged from hospital. RESULTS: All three computerised systems seemed to give satisfactory control compared with the traditional dosing method. For patients receiving more intensive treatment with an assigned target range of 3.0-4.5 computerised dosage programs achieved significantly better control; the medical staff undertreated such patients almost 50% of the time. CONCLUSION: Computer based programs can assist outpatient anticoagulant control with warfarin during both early and long term treatment. For most patients the control achieved is as good as that obtained by the customary method of dosing, by experienced clinic doctors, although the latter tend to be too conservative when dosing patients within the intense target range of 3.0 to 4.5 International Normalised Ratio (INR). The computers were significantly more successful in this higher range. PMID- 8496385 TI - Geographical variation in prevalence of hepatitis B virus DNA in HBsAg negative patients. AB - AIMS--To study the geographical variation of the prevalence of hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg) negative subjects. METHODS--A nested polymerase chain reaction (PCR) assay was used to amplify the core region of HBV. The assay was able to detect 10 molecules of a full length HBV plasmid. RESULTS--When applied to HBsAg negative paraffin wax embedded liver samples from Italy, Hong Kong, and the United Kingdom, a geographical variation in the prevalence of HBV-DNA positivity was noted. Two of 18 (11%) of Italian samples and 2/29 (6.9%) of Hong Kong samples were positive for HBV-DNA while none of the 70 cases from the United Kingdom was positive by nested PCR. Contamination by plasmid DNA was excluded using a novel method based on heteroduplex formation. One HBV-DNA positive case had idiopathic chronic active hepatitis, but the diagnoses in the other three HBV-DNA positive cases did not suggest any aetiological connection between HBV-DNA positivity and liver pathology. CONCLUSIONS--HBV-DNA could be detected in the liver tissues of a proportion of HBsAg negative subjects. The prevalence of such cases is related to the endemic rate of a geographical region. The use of HBV PCR on paraffin wax embedded tissues will be valuable for future studies on the molecular epidemiology of HBV. PMID- 8496386 TI - Evaluation of non-radioactive trivalent DNA probe (LT, ST1a, ST1b) for detecting enterotoxigenic Escherichia coli. AB - AIMS: To evaluate a digoxigenin-labelled trivalent DNA probe (LT, ST1a, ST1b) for detecting enterotoxigenic Escherichia coli (ETEC), by comparison with a cell culture assay for detecting LT, individual DNA probes for LT, ST1a and ST1b, and an enzyme immunoassay for detecting ST1. METHODS: A 1268 base pair DNA fragment, containing parts of the genes for E coli heat labile enterotoxin (LT) and heat stable enterotoxins (ST1a and ST1b), was random prime labelled with digoxigenin dUTP. The labelled DNA was used as a probe in colony hybridisation reactions to examine 180 E coli strains of which 92 had previously been shown by a cell culture assay to produce LT. Six LT negative ST1 positive E coli, 34 Verotoxin producing E coli (VTEC), and 84 organisms from other genera were also examined. All organisms other than VTEC were isolated from travellers returning from abroad with diarrhoea. All E coli strains were retested by cell culture for LT, and were tested by enzyme immunoassay (EIA) for ST1, and by the trivalent and individual DNA probes. RESULTS: All 81 isolates, that on retesting by cell culture were positive for LT, also hybridised with the trivalent and LT probes; 27 of these were also enzyme immunoassay (EIA) positive for ST1 of which 24 hybridised with the ST1b probe and three with the ST1a probe. Of 99 isolates, that on retesting by cell culture were negative for LT, all were negative by LT probe and only three were EIA positive for ST1; these three were positive by both trivalent and ST1b probes. Four isolates were positive by the trivalent probe but negative by cell culture and EIA; all four were positive by ST1b probe. Compared with the cell culture assay for LT, the probe had a sensitivity and specificity both of 100%; compared with the EIA for ST1, the probe had a sensitivity of 100% and specificity of 88%. CONCLUSIONS: The trivalent DNA probe is a sensitive, specific, and reliable method for detecting ETEC that should be considered for use by diagnostic microbiology laboratories. PMID- 8496387 TI - Detection of Chlamydia pneumoniae and Chlamydia psittaci in sputum samples by PCR. AB - AIMS: To use the polymerase chain reaction (PCR) to detect Chlamydia pneumoniae and Chlamydia psittaci in sputum samples. METHODS: A nested PCR was developed, the first stage of which amplified DNA from both C pneumoniae and C psittaci while the second stage targeted specifically at C pneumoniae, allowing the two species to be differentiated. The primers were designed not to amplify sequences from C trachomatis. A panel of 26 sputum samples from patients with community acquired pneumonia evaluated previously by enzyme linked immunosorbent assay (ELISA), direct immunofluorescence (DIF), and culture was tested blind by PCR. Most of these specimens also had accompanying serial serum samples which were tested for species specific antibodies using microimmunofluorescence (micro-IF). RESULTS: PCR detected C pneumoniae DNA in 10 of the 26 samples and C psittaci DNA in four. There was good concordance between ELISA, DIF, micro-IF and PCR in the C pneumoniae group. Two of the C psittaci identified by PCR were labelled C pneumoniae by DIF but the PCR results were supported by serology or a history of bird contact. Of the PCR negative group: six were true negative results; two contained C trachomatis. There were four discrepant results. CONCLUSIONS: The data suggest that PCR is effective in the detection of C pneumoniae. The sensitivity for C psittaci is inevitably lower due to the strategy taken but specificity seemed to be good. PMID- 8496388 TI - Use of PCR in routine diagnosis of treated and untreated pulmonary tuberculosis. AB - AIMS: To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. METHODS: A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong. RESULTS: An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. CONCLUSION: This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis. PMID- 8496389 TI - Distribution of O-acetylated sialomucin in the normal and diseased gastrointestinal tract shown by a new monoclonal antibody. AB - AIMS: To produce and characterise a monoclonal antibody specific for O-acetylated sialomucin and to assess its use in immunohistochemistry on a panel of normal and diseased intestinal tissue samples. METHODS: Mouse monoclonal antibodies were developed following immunisation with highly purified human colonic mucin. One of these (MMM-17) showed strong binding to mucin throughout the normal colon with relative lack of binding to colon cancer tissue. The binding epitope of MMM-17 was then characterised by screening for agglutination activity against a panel of human and animal erythrocytes and by assessment of its binding to a range of normal and chemically treated slot blotted mucins. Further immunohistochemical studies were then performed on formalin fixed, normal, and diseased human intestinal samples. RESULTS: Binding of MMM-17 to slot blotted human colonic mucin was reduced by 38 (SD 14%) (n = 4) by alkali treatment of the mucin, sequential alkali and sialidase treatment completely abolished binding. Sialidase treatment alone, however, caused only an 11 (11%) reduction in binding. MMM-17 failed to agglutinate any human, rabbit, rat or mouse erythrocytes. These findings were compatible with specificity of MMM-17 for sialomucins O-acetylated at the C-7 or C-8 positions on the sialic acid. Strong staining by MMM-17 was found in all goblet cells throughout all 40 normal colonic and rectal samples studied, but staining was absent in seven of 13 colorectal carcinomas. Normal duodenum (n = 16) and normal ileum (n = 3) all showed occasional positive goblet cells. The normal gastric antral mucosa was generally negative B MMM-17, but in all of 15 cases of gastritis with intestinal metaplasia the metaplastic glands were strongly positive for MMM-17. CONCLUSION: Monoclonal antibody MMM-17 has specificity for O-acetylated sialomucins and its binding depends both on the position of O-acetylation and on the adjacent oligosaccharide structure. Preliminary studies using the antibody on archival tissue samples support the previous reports of reduced O-acetylation in colon cancer demonstrated by indirect histochemistry and show the neo-formation of O-acetylated sialomucin in intestinal metaplasia in the stomach. PMID- 8496390 TI - Overexpression of p53 protein in Barrett's syndrome with malignant transformation. AB - AIMS: To study the overexpression of p53 protein in Barrett's oesophagus with adenocarcinoma, and to correlate this expression with the pathological features of Barrett's syndrome. METHODS: Immunohistochemical staining was performed on frozen sections with a monoclonal antibody directed against wild type and mutated p53 protein (Pab 1801). Eleven cases of Barrett's adenocarcinoma were studied, seven of which had extensive sampling of benign Barrett's mucosa. RESULTS: Eight of 11 adenocarcinomas overexpressed the p53 protein. Both early and advanced tumours were positive. In Barrett's mucosa around the p53 positive tumours, high grade dysplasia was positive; low grade dysplasia and non-dysplastic mucosa were negative. CONCLUSIONS: P53 gene mutation with ensuing p53 protein overexpression is a common feature of Barrett's adenocarcinoma, both at early and advanced stages. This mutation appears as a relatively late event during the neoplastic transformation of Barrett's oesophagus. PMID- 8496391 TI - Cytokine gene expression in skin and lymphoid organs in graft versus host disease. AB - AIM: To determine if human graft versus host disease (GvHD) is associated with any detectable change in cytokine gene expression in the skin and lymphoid organs. METHODS: Reverse transcriptase and the polymerase chain reaction were used to amplify mRNA for interleukins-1 (IL-1), -2 (IL-2), -4 (IL-4) and -6 (IL 6), IL-2 receptor (IL-2R), tumour necrosis factors alpha (TNF-alpha) and beta (TNF-beta), gamma interferon (IFN gamma) and granulocyte macrophage colony stimulating factor (GM-CSF) in frozen punch biopsy specimens of skin and necropsy samples of skin, lymph node, and spleen. RESULTS: No cytokine mRNA was detected in the punch biopsy specimens except weak signals for IL-6 and IL-1 and GM-CSF in two normal donors and IL2-R in one patient with GvHD. In samples of skin taken at necropsy, however, significant quantities of mRNA for TNF-alpha, TNF-beta, and IL 4 were detected in patients who had or had had GvHD in contrast to those without the disease whose skin lacked mRNA for these products but contained detectable quantities of IL-1, IL2-R, IL-6 and GM-CSF. There seemed to be a reciprocal relation between TNF-alpha and IL-4. In necropsy samples of lymph node and spleen a pattern of cytokine production similar to that in the skin was observed with a preponderance of TNF-alpha, TNF-beta and IL-4 in patients with GvHD and GM-CSF and IL-6 in those without the disease. CONCLUSIONS: The local synthesis of these molecules would explain many of the morphological and immunohistological features of GvHD. The failure to detect TNF-alpha, TNF-beta, and IL-4 in skin biopsy specimens exhibiting GvHD is probably due to their small size but further investigations are required. PMID- 8496392 TI - Diagnosis of complete molar pregnancy by microsatellites in archival material. AB - AIMS: To develop an assay which would determine the parentage of hydatidiform molar pregnancies. METHODS: DNA was extracted from formalin fixed, paraffin wax embedded tissue from hydatidiform molar pregnancies and spontaneous abortions after separation of chorionic villi and decidua. PCR amplification of dinucleotide repeat sequences ("microsatellites") was performed using three different primers. Products were radioactively labelled and visualised by autoradiography of dried polyacrylamide gels. RESULTS: With informative microsatellites, diagnostic patterns of amplification were obtained. Complete moles yielded either one or two microsatellites which differed from both maternal (decidual) microsatellites. Complete mole could be excluded by all the microsatellites showing alleles identical with those in maternal DNA. CONCLUSIONS: This technique offers a method of determining the presence of entirely paternal alleles in a molar pregnancy and thus confirming a complete hydatidiform mole. PMID- 8496393 TI - Oestrogen and progesterone receptor expression in mammary fibromatosis. AB - AIMS: To investigate the oestrogen and progesterone receptor concentrations expressed on mammary fibromatoses to determine their responsiveness to oestrogenic stimuli. METHODS: Six mammary fibromatoses were examined using immunohistochemistry for the presence of oestrogen and progesterone receptors using antibodies against the receptor proteins. Enzyme immunoassays (EIAs) using the same antibodies were also performed in four patients. Immunohistochemical staining for pS2 protein was also carried out as a measure of functional oestrogen receptors. RESULTS: Neither receptor nor pS2 protein was expressed using immunohistochemistry. Very low concentrations of both oestrogen and progesterone receptors were shown by EIA. CONCLUSION: These results indicate the absence of clinically important concentrations of oestrogen and progesterone receptors in breast fibromatoses and suggest that treatment directed against oestrogen is unlikely to be beneficial. PMID- 8496394 TI - Response analysis in histopathology external quality assessment schemes. AB - AIMS: To develop a computerised method for analysing the results of histopathology external quality assessment (EQA) schemes which can provide confidential personal reports to individual participating pathologists. METHODS: A program was developed using the OMNIS database system, running on Apple Macintosh or IBM compatible computers. RESULTS: The program produces a general report of participants' responses to each case, and a choice of two types of personal report. One of these provides a list of the participant's diagnoses with a list of the most popular (Consensus) diagnoses for comparison. The other provides automatically calculated scores for the pathologist's performance along with simple statistical evaluation. The scores can be calculated by comparison with the consensus of the group or with correct diagnoses if they are known. A histogram indicating the distribution of performance within the group can be produced. The program can accept uncertainty in the form of differential diagnosis lists from participants. Potentially dangerous diagnostic errors can be identified and handled separately. Participants are identified only by code numbers and confidentiality can easily be enforced. The program is currently being used in the national renal pathology EQA scheme and in the local general histopathology scheme in the East Midlands. CONCLUSIONS: This program offers solutions to problems which have bedevilled the organisers of histopathology EQA schemes. It offers confidential advice to pathologists and will help to identify areas where an individual might benefit from continuing career grade medical education. It raises the possibility of the development of nationally agreed standards of performance in the reporting of pathological specimens, and it may be applicable to other specialties where textual reports are produced. PMID- 8496395 TI - Effect of beta propiolactone on specific antibody measurements by ELISA. AB - Serum samples from 30 HIV seronegative patients were treated with beta propiolactone (BPL) to determine whether BPL interfaces with ELISA for specific antibodies against protein and carbohydrate antigens. BPL had no discernible effect on specific antibody measurements by ELISA. With the measuring need for specific antibody measurements in the management of HIV seropositive patients, it is reassuring that this laboratory safety measure does not impair the reliability of results. PMID- 8496396 TI - Foamy changes of placental cells in probable beta glucuronidase deficiency associated with hydrops fetalis. AB - Mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency) has been described in association with non-immune hydrops fetalis. Three consecutive pregnancies in an itinerant family, which resulted in stillbirths caused by non immune hydrops are described. The parents were closely related and there was a strong family history of storage disorders. The main clue to the diagnosis, however, came from the presence of pronounced foamy cytoplasmic change in the villous Hofbauer cells of the placenta. This raised the possibility of an inherited metabolic storage disorder. The parents were subsequently shown to have beta glucuronidase activities in the heterozygous range in leucocytes and fibroblasts which suggested that the non-immune hydrops was caused by beta glucuronidase deficiency. PMID- 8496397 TI - Antibacterial action of the urease inhibitor acetohydroxamic acid on Helicobacter pylori. AB - The urease inhibitor acetohydroxamic acid (AHA) was assessed for its bacteriostatic and bactericidal effects on Helicobacter pylori. For eight isolates of H pylori, the minimum inhibitory concentration (MIC) was either 200 mg/l or 400 mg/l. Interactions between AHA and antimicrobial drugs used to treat H pylori were also determined. For most isolates AHA reduced the MIC for colloidal bismuth subcitrate (CBS), tetracycline, metronidazole, and amoxicillin. In a few isolates, however, AHA increased the minimum bactericidal concentration (MBC) for these antimicrobial treatments. In vitro AHA is active against H pylori and it interacts with other agents directed against H pylori. PMID- 8496398 TI - Lymphocytic mastopathy associated with infiltrating lobular breast carcinoma. AB - A case of lymphocytic mastopathy (LM) and concomitant infiltrating lobular breast carcinoma is described. The inflammatory infiltrate cuffed areas of carcinoma. The LM changes also affected lobules that had not been infiltrated by the carcinoma, although adjacent areas contained both in situ and infiltrating tumour. A minor portion of the inflammation was distributed throughout the ducts. The striking lobulocentricity of the inflammatory infiltrate corresponds to previous reports of LM, and distinguishes this case from the inflammatory response commonly associated with breast carcinomas. It is highly likely that the breast carcinoma induced the LM changes in lobules not yet harbouring tumour. PMID- 8496399 TI - A viscometric method of measuring plasma fibrinogen concentration. PMID- 8496400 TI - Comparison of electron microscopy and immunocytochemistry in tumour diagnosis. PMID- 8496401 TI - Bone marrow trephine biopsy in lymphoproliferative disease. PMID- 8496402 TI - Glutathione S-transferase expression in primary biliary cirrhosis supports concept of "ductular metaplasia" of hepatocytes. PMID- 8496403 TI - Acanthamoeba keratitis. PMID- 8496404 TI - Detection of cobalamin deficiency using the urinary methylmalonic acid test by gas chromatography mass spectrometry. PMID- 8496405 TI - Immune response and host resistance of humans to dermatophyte infection. AB - Clearing of dermatophyte infection depends on a cell-mediated immune response. Antibodies to fungi, although present in infected persons, are ineffective at ridding the skin of fungi. Experiments in which human volunteers were deliberately infected with dermatophytes identified two major groups on the basis of cellular immune responsiveness: (1) those who mount decisive delayed-type hypersensitivity that results in clearing of the infection, and (2) those who have absent or defective cellular immunity that prevents them from mounting an effective response to dermatophytes and thus predisposes them to chronic or recurrent dermatophyte infection. The courses of experimental infection in these two groups were compared with skin test results. The presence of an acute inflammatory infection was correlated with delayed-type (T-cell-mediated) hypersensitivity to a trichophytin skin test and the ability of persons affected in this manner to achieve mycologic cure. In contrast, chronic infection was associated with high immediate (anti-Trichophyton-IgE-mediated) hypersensitivity and low or waning delayed-type (T-cell-mediated) hypersensitivity to trichophytin. Despite this immune deficiency, these persons had a normal response to other infectious agents and skin test antigens. This type of selective and perhaps induced immune deficit may be relatively common, because persons chronically infected with a dermatophyte constitute 10% to 20% of the general population. PMID- 8496406 TI - Suppression of immunity and inflammation by products produced by dermatophytes. AB - When normal, previously uninfected hosts are exposed to dermatophytes under experimental occlusive conditions, infections develop and cell-mediated immunity is induced. Subsequent exposure to dermatophytes under the same conditions elicits an immune response that is capable of curing the infection, once occlusion is removed. Lymphocytes or monocytes involved in the immune response may produce cytokine growth factors that foster stratum corneum turnover and shedding of the fungus from the skin surface. Chronic dermatophyte infections develop when conditions of the local environment or virulence factors of the fungus outweigh the capabilities of cell-mediated immunity, or when a person does not develop cell-mediated immunity to fungal antigens. Even if immunity does develop, certain dermatophytes such as Trichophyton rubrum produce substances that diminish the immune response. One class of these substances, the mannans, can indirectly inhibit stratum corneum turnover. A nonresponsive host immune system or the suppression of the immune response by products produced by dermatophytes can prevent complete eradication of the fungus or predispose to reinfection. PMID- 8496407 TI - Pathophysiology of dermatophyte infections. AB - Dermatophyte infections are among the most common infections encountered in medicine. Often considered trivial, these infections are in fact frequently refractory and recurrent. This article presents an overview of the causes, symptoms, differential diagnosis, and clinical course of the most prevalent dermatophyte infections: tinea pedis, tinea cruris, tinea capitis, tinea corporis, and onychomycosis. Complicated situations such as follicular involvement, dermatophytoses in patients who are immunocompromised, and the exaggerated response to zoologically acquired fungal infections are also discussed. PMID- 8496408 TI - Topical antifungal drugs in the treatment of tinea pedis, tinea cruris, and tinea corporis. AB - Topical treatment of fungal infections took a step forward in the 1960s with the introduction of biologically active agents with specific antifungal mechanisms of action. Most modern broad-spectrum antifungal agents act by blocking specific steps in the synthesis of fungal cell membrane components. The broad-spectrum topical antifungal drugs now in use include the imidazoles (e.g. clotrimazole and miconazole), a pyridone-ethanolamine salt, dimethylmorpholines, and the newest class, the allylamines (e.g., naftifine and terbinafine). The topical allylamines have been shown in comparative studies to produce higher cure rates and more rapid responses in dermatophyte infections than many of the older agents. PMID- 8496409 TI - Mechanisms of action of systemic antifungal agents. AB - An understanding of the mechanisms of action and in vitro profiles of antifungal agents is pivotal to selecting effective treatments for dermatophytoses. The principal mechanisms of action of antifungal drugs include disruption of spindle and cytoplasmic microtubule function (e.g., griseofulvin), depletion of or binding to ergosterol (e.g., terbinafine, ketoconazole, and amphotericin B), and accumulation of squalene (terbinafine). It is likely that antifungal agents that deplete or bind to ergosterol have fungistatic activity only; agents that produce a concomitant accumulation of intracellular squalene have fungicidal activity. Although the mechanism of action markedly influences the clinical efficacy of an antifungal agents, in vitro and in vivo antimycotic profiles and bioavailability factors such as drug access to the stratum corneum also contribute to the effectiveness of antifungal agents. PMID- 8496410 TI - Progression of interdigital infections from simplex to complex. AB - The dynamics of symptomatic toe web infections often involve an ecologic interplay in which an initial dermatophyte infection provides a hospitable niche for subsequent colonization by bacteria. Several studies suggest that exacerbation of a mild dermatophyte infection (dermatophytosis simplex) can arise in the occlusive environment of the toe web space. Fungal infection induces damage to the stratum corneum, which allows overgrowth of resident bacteria and maceration, itching, and often malodor at the site (dermatophytosis complex). Because fungi frequently elaborate antibacterial substances, the superinfecting bacteria generally are resistant to penicillin and other antibiotics. A flourishing bacterial superinfection may mask the underlying fungal cause, making it difficult to obtain a positive fungal culture. PMID- 8496411 TI - Androgen biology as a basis for the diagnosis and treatment of androgenic disorders in women. I. AB - Disorders of androgen excess in women are common in the practice of dermatology. The literature regarding the evaluation and treatment of women with cutaneous hyperandrogenism (acne, hirsutism, and alopecia) is vast and is contained in numerous subspecialty journals. At first glance, the basic science knowledge required to understand androgen biology appears exceedingly complex. However, an understanding of androgen physiology and a familiarity with the relevant literature are the basis of appropriate evaluations and treatment recommendations. In the first of this two-part series, we review the basic science of androgen biology and pathophysiology in women. The second part of this series will cover the evaluation of suspected hyperandrogenic women and the therapeutic modalities that are available. PMID- 8496412 TI - Clinical and immunologic studies in reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin. AB - BACKGROUND: Little is understood about reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin. OBJECTIVE: Our purpose was to define reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin further with focus on immunologic studies. METHODS: In patients with reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin, we measured circulating immune complexes before, during, and after therapy. We examined natural killer cells in a functional assay; we performed direct immunofluorescence and T- and B-cell marker studies in skin biopsy specimens. RESULTS: The infiltrate in reticular erythematous mucinosis is composed of helper T cells. Circulating immune complexes are increased in both reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin and decrease with hydroxychloroquine therapy and clinical clearing. Natural killer cell function is decreased in reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin. CONCLUSION: Changes in circulating immune complex titers accompanying therapy with hydroxychloroquine and clinical clearing, with recurrence of the condition and increase in circulating immune complexes on discontinuation of treatment, point to a possible relation between these events. PMID- 8496413 TI - Atopic dermatitis in children: who cares? Who pays? AB - BACKGROUND: Atopic dermatitis is an important cause of morbidity in children of all ages. Despite its high prevalence, there has been no examination of ways in which care for atopic dermatitis is delivered. OBJECTIVE: This study reviewed the costs for care of childhood atopic dermatitis in an urban setting and estimated the national cost for treatment of the disease. METHODS: We used data from one children's hospital to study the use of the emergency room for atopic dermatitis and used national data sets to estimate the cost of care in the United States. RESULTS: A large proportion of visits occur in the emergency department, during daytime office hours, and mostly by patients who have public insurance. The total national cost for treatment of childhood atopic dermatitis is $364 million annually, which is a conservative estimate. CONCLUSION: Given its high prevalence, associated morbidity, and cost, resources must be better allocated to improve the organization of care for patients with atopic dermatitis. PMID- 8496414 TI - Wegener's granulomatosis: cutaneous and oral mucosal disease. AB - BACKGROUND: Wegener's granulomatosis is a complex disease that can be difficult to diagnose, especially if the classic triad of necrotizing granulomas of the respiratory tract, generalized vasculitis, and glomerulitis are not present. A delay in diagnosis may result in irreversible kidney damage and ultimately death. OBJECTIVE: This study was done to identify clinical and histologic findings of the skin and oral mucosa that may aid in the diagnosis of this disease. METHODS: The records of 40 patients with Wegener's granulomatosis were reviewed. RESULTS: Of these patients 12 had cutaneous lesions, 2 had oral mucosal lesions, and 2 had both cutaneous and oral mucosal lesions. Cutaneous and oral mucosal lesions were a presenting sign in 10% and 5% of patients, respectively. Overall, 25% demonstrated at least one of the specific cutaneous histopathologic findings described for Wegener's granulomatosis, that is, necrotizing vasculitis, granulomatous vasculitis, and palisading granuloma. One patient had gingival hyperplasia with petechiae, considered to be pathognomonic for Wegener's granulomatosis. CONCLUSION: This study demonstrates that cutaneous or oral mucosal findings may serve as valuable diagnostic aids when evaluating a patient suspected of having Wegener's granulomatosis. PMID- 8496415 TI - Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample. AB - BACKGROUND: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. OBJECTIVE: Our purpose was to evaluate and expand previous findings on the incidence of atopic dermatitis and its concordance rates in twins. METHODS: A mailed questionnaire study was conducted. It involved 812 twin pairs living in Fyn County, Denmark, as of Jan. 1, 1987 and born between 1965 and 1979. Zygosity was determined by the similarity method. RESULTS: The response rate was 92%. The cumulative incidence rate (up to 7 years) of atopic dermatitis increased significantly from 0.06 for the birth cohort 1965-1969 to 0.12 for the birth cohort 1975-1979. The pairwise concordance rate was 0.72 in monozygotic and 0.23 in dizygotic twin pairs. CONCLUSION: The frequency of atopic dermatitis is still increasing but not as rapidly as in the 1960s. The magnitude of the concordance rates indicates that genetic factors are decisive in the development of atopic dermatitis. It is suggested that widespread environmental factors are operating in genetically susceptible persons. PMID- 8496416 TI - Alcohol intake and treatment responsiveness of psoriasis: a prospective study. AB - BACKGROUND: Alcohol has been reported to be a risk factor in psoriasis mainly based on the observation that there is a higher prevalence of alcohol abuse in persons with psoriasis, especially in men. OBJECTIVE: We prospectively examined the relation between pretreatment average daily ethanol consumption and treatment outcome in inpatients with moderate to severe psoriasis. METHODS: The severity of psoriasis of 94 inpatients (48 men and 46 women) was assessed before and after treatment. Ethanol use was determined by obtaining the patients' reports of their average daily consumption of alcoholic beverages during the 6 months before admission. RESULTS: The average daily ethanol intake of more than 80 gm before treatment was more frequently associated with less treatment-induced improvement (less than 10%) (p = 0.02) in the percentage of the total body surface area affected by psoriasis in men but not in women. CONCLUSION: Ethanol abuse may have an adverse effect on treatment outcome in men with psoriasis. PMID- 8496417 TI - High prevalence of skin cancer in World War II servicemen stationed in the Pacific theater. AB - BACKGROUND: A large proportion of our World War II patients with skin cancer had been stationed in the Pacific. OBJECTIVE: Our purpose was to determine whether a statistically greater number of World War II servicemen with skin cancer were stationed in the Pacific than the number stationed in Europe. METHODS: In a consecutive survey of 370 World War II servicemen with skin cancer who were stationed abroad, place of service, skin cancer types, skin type, ethnic background, and estimated average hours outdoors per day during their lifetime were determined. The number of veterans stationed in the Pacific and the number stationed in Europe with respect to these data were analyzed with the chi-square test. RESULTS: A statistically significantly greater number of Pacific veterans than Europe veterans had basal cell or squamous cell carcinomas. CONCLUSION: A few months to a few years of prolonged sun exposure in a high-sun-intensity area may result in skin cancer development many years after exposure. PMID- 8496418 TI - Reduced lymphocyte subpopulations in patients with advanced or disseminated melanoma. AB - BACKGROUND: Studies have revealed many features of lymphocyte behavior in patients with malignant melanoma, but there are conflicting results. OBJECTIVE: The aim of this study was to measure with easily reproducible assays the circulating lymphocytes and other immunologic aspects in 33 patients with advanced or disseminated malignant melanoma (MM). METHODS: The following variables were measured: circulating monocytes; total lymphocytes; B (CD19) and T cell subpopulations; CD3, CD4, and CD8, natural killer cells (anti-Leu-7+ or CD57 and anti-Leu-11+ or CD16) (cytofluorimetry); plasma levels of IgG, IgA, IgM, and IgE; complement fractions 3, 4, and 1Q; antibodies against foreign microorganisms (AaM) (adeno, herpes simplex, herpes zoster, measles, parotitis, cytomegalo, Epstein-Barr, and rubella viruses) and Toxoplasma; and cutaneous delayed hypersensitivity (CDH) to recall antigens (tetanus, diphtheria, Streptococcus, tuberculin, Proteus, Trichophyton, and Candida). We also studied 96 healthy persons, matched for age and geographic location, who were tested on the same days as the patients. RESULTS: In MM the number of total lymphocytes and subsets CD19, CD3, CD4, and CD8 was decreased from 25% to 40% (p < 0.001). The CD4/CD8 ratio increased (22%, p < 0.005) because of the relatively greater decrease of CD8. The CD57 and CD16 cells (expression of natural killer lymphocytes) were consistently reduced (30%; p < 0.002 to p < 0.003). C3 serum level was increased (30%; p < 0.001). Immunoglobulins, CDH, AaM, and all other tests were the same in the two groups. CONCLUSION: The single most important result seems to be a reduction of CD57 and CD16 cells in patients with advanced MM. PMID- 8496419 TI - Use of the alexandrite laser (755 nm, 100 nsec) for tattoo pigment removal in an animal model. AB - BACKGROUND: All previous treatment modalities for the removal of tattoos, with the possible exception of the Q-switched ruby and YAG lasers, result in scarring. OBJECTIVE: The purpose of this study was to investigate the use of a new laser that may remove tattoo pigment without leaving a scar. METHODS: A Yucatan micropig was tattooed by a professional tattoo artist with black, blue, green, and red pigments. These tattoos were then treated with single overlapping pulses with the alexandrite laser (wavelength 755 nm, pulse 100 nsec) and evaluated clinically and histologically. Comparison treatment with an argon laser (wavelength 488 nm, 514 nm, continuous-wave) and flashlamp-pumped dye laser (wavelength 585 nm, pulse 450 microseconds) was performed as well for removal of red tattoo pigment. RESULTS: The alexandrite laser was found to be very effective in removal of professional and amateur black tattoo pigment, moderately effective in removal of blue and green pigment, and minimally effective in removal of red pigment. No scarring was seen clinically or histologically. CONCLUSION: The alexandrite laser shows promise as a treatment modality for tattoo removal without scarring. PMID- 8496420 TI - Microscopic features of lichen sclerosus et atrophicus in acrochordons: a clue to the cause of lichen sclerosus et atrophicus? AB - BACKGROUND: The cause of lichen sclerosus et atrophicus (LSA) is unknown, but on the penis it is associated with chronic occlusion, that is, phimosis. Microscopic changes of LSA were seen unexpectedly in two acrochordons. OBJECTIVE: Our purpose was to further characterize this phenomenon. METHODS: A total of 449 acrochordons examined in our histopathologic laboratory in the past 2 years were studied for changes of LSA, and clinical data were collected. RESULTS: Eight additional cases were found. All of the acrochordons exceeded 0.5 cm, and three were 1 cm or larger. At least six were under chronic occlusion or pressure. The dermal changes of LSA predominated over the epidermal changes. All showed collagenous homogenization, sclerosis, and inflammation. Elastic fibers were characteristically decreased. CONCLUSION: These observations strengthen the evidence that LSA in flaccid skin may be caused by chronic occlusion. PMID- 8496421 TI - Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. AB - BACKGROUND: Vertical sections of small scalp biopsy specimens are often inadequate for the diagnosis of male pattern androgenetic alopecia (MPAA). Quantitative analysis of follicular structures in horizontal sections can provide more information. OBJECTIVES: Our purpose was to establish better diagnostic criteria by comparing horizontal and vertical sections of scalp biopsy specimens from MPAA and normal control subjects and to determine the predictive value of horizontal sections, by relating counts of follicular structures in MPAA to subsequent hair regrowth from topical minoxidil therapy. METHODS: Paired 4 mm punch biopsy specimens were taken from 22 normal control subjects and 106 patients with MPAA, for horizontal and vertical sectioning. In horizontal sections, hair bulbs, terminal anagen, catagen and telogen hairs, telogen germinal units, and vellus hairs were counted, as were follicular units and stelae. RESULTS: The diagnosis of MPAA was confirmed by finding decreased terminal hairs and increased stelae and vellus hairs. The average horizontal section contained 22 terminal and 13 vellus hairs, a 1.7:1 ratio. Changes compatible with MPAA were found in most vertical and horizontal sections, but horizontal sections were required for follicular counts and showed terminal:vellus hair ratios diagnostic of MPAA in 67% of cases. Of 44 patients treated with topical minoxidil, five with less than 2 follicular structures/mm2 showed no hair regrowth, 32 with 2 to 4 follicular structures/mm2 showed regrowth in 72%, and seven with more than 4 follicular structures/mm2 showed regrowth in 86% of cases. In MPAA with no significant inflammation, regrowth occurred in 77% of cases, versus 55% in cases with significant inflammation. CONCLUSION: Horizontal sections of scalp biopsy specimens in MPAA provide more diagnostic information than vertical sections and appear to have a predictive value for hair regrowth. PMID- 8496422 TI - Antimalarials for children: indications, toxicities, and guidelines. AB - The use of antimalarial drugs in children has been discussed extensively in the rheumatology literature, but there is scant information in the dermatology literature. We discuss indications, dosing, administration, and side effects of antimalarial drugs in children as well as skin diseases in children who have been treated with chloroquine or hydroxychloroquine. PMID- 8496423 TI - Treatment of nonhairy melanocytic macules by dermabrasion and topical application of 5% hydroquinone monobenzyl ether cream. PMID- 8496424 TI - Vitiligo: treatment by dermabrasion and epithelial sheet grafting--a preliminary report. PMID- 8496425 TI - Neutrophilic eccrine hidradenitis. PMID- 8496426 TI - Bilateral basal cell carcinoma of the breasts. PMID- 8496427 TI - An open prospective clinical trial with systemic ranitidine in the treatment of psoriasis. PMID- 8496428 TI - Dapsone-associated agranulocytosis and severe anemia in a patient with leukocytoclastic vasculitis. PMID- 8496429 TI - Treatment of Hailey-Hailey disease by dermabrasion. PMID- 8496430 TI - Local tolerability of topically applied methylprednisolone aceponate. PMID- 8496431 TI - Systemic effects of topically applied methylprednisolone aceponate in healthy volunteers. PMID- 8496432 TI - Yellow nail syndrome in a patient with mycosis fungoides. PMID- 8496433 TI - Cimetidine therapy for multiple viral warts in children. PMID- 8496434 TI - Mucinous nevus. PMID- 8496435 TI - Foscarnet-induced vulvar erosion. PMID- 8496436 TI - A theorem of pruritus and urticarial diminution. PMID- 8496437 TI - Eruptive syringoma. PMID- 8496438 TI - Association between cheilitis granulomatosa and Crohn's disease. PMID- 8496439 TI - Cutaneous lupus erythematosus. PMID- 8496440 TI - Hydrochlorothiazide-induced lupus erythematosus: a new variant? PMID- 8496441 TI - Interobserver agreement in a community skin cancer screening setting. PMID- 8496442 TI - Pyoderma gangrenosum treated successfully with potassium iodide. PMID- 8496443 TI - A statistical survey of melanomas of the foot. PMID- 8496444 TI - Rombo syndrome: a second case report and review. PMID- 8496445 TI - Efficacy of cyclosporine in two patients with dermatitis herpetiformis resistant to conventional therapy. PMID- 8496446 TI - Familial cutaneous heterotopic meningeal nodules. PMID- 8496447 TI - 6-Thioguanine therapy for psoriasis causing toxic hepatic venoocclusive disease. PMID- 8496448 TI - Treatment of Mycobacterium chelonae-induced skin infection with clarithromycin. PMID- 8496449 TI - Purpuric pityriasis rosea. PMID- 8496450 TI - Tinea corporis in wrestlers. PMID- 8496451 TI - Does photopheresis reduce the tumor cell burden in erythrodermic cutaneous T-cell lymphoma? PMID- 8496452 TI - Publication bias in pharmaceutical industry-sponsored research. PMID- 8496453 TI - Androgen biology as a basis for the diagnosis and treatment of androgenic disorders in women. II. AB - In the May 1993 issue of the Journal we reviewed the basic science of androgen biology in women. We now discuss the evaluation of suspected hyperandrogenism and the therapeutic modalities available. PMID- 8496454 TI - Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus. AB - BACKGROUND: Erythema elevatum diutinum (EED) is a rare, chronic form of cutaneous vasculitis that can result in fibrosis. Four patients infected with the human immunodeficiency virus (HIV) had unusual nodular lesions of EED. OBJECTIVE: Our purpose was to document the occurrence of these lesions in HIV-infected patients and to characterize the histopathologic and immunophenotypic features of nodular EED. METHODS: Clinicopathologic studies were supplemented by special stains of biopsy specimens. RESULTS: EED may be a complication of HIV infection. Nodules of EED are composed of small aggregates of Mac-387+ spindled cells. Within the aggregates can be seen neutrophils, nuclear dust, and fibrin. The marked fibrosis of the lesions may account for the lack of response to dapsone. CONCLUSION: EED should be considered in the differential diagnosis of juxta-articular nodules in HIV-infected patients; its diagnosis can be confirmed by biopsy. PMID- 8496455 TI - Amplified surface microscopy. Preliminary evaluation of a 400-fold magnification in the surface microscopy of cutaneous melanocytic lesions. AB - BACKGROUND: Surface microscopy (SM) opened a new dimension in the clinical assessment of cutaneous pigmented lesions. Diagnostic patterns were described to provide guidelines for the preoperative diagnosis of pigmented skin lesions. OBJECTIVE: Our purpose was to explore whether "amplified" surface microscopy (ASM), by increasing magnification up to 400-fold, provides any improvement in the analysis of patterns previously described in cutaneous pigmented lesions. METHODS: A fiber-optic camera, allowing magnification up to 400 times and associated with an imaging system computer, was used for the analysis of 40 melanocytic lesions. Special emphasis was put on the most important features that can be observed in surface microscopy, the so-called pigment network and brown globules. RESULTS: The lines (grids) of the pigment network appeared to be composed of three zones: two darker external lines and one central clearer zone. This pattern, not previously seen with SM, is compatible with the anatomy of pigment accumulation in the epidermal rete ridges. Two types of brown globules could be distinguished: one located in the center of the pigment network holes, the other on the lines of its grids. The "on-the-grid" type was smaller than the "in-the-hole" type; it could be misinterpreted as "black dots" when seen at lower magnification (x10). CONCLUSION: ASM is a tedious procedure that may help in the analysis of the features previously recognized by SM; SM is more accessible for routine use. PMID- 8496456 TI - Mucocutaneous leishmaniasis: a clinicopathologic classification. AB - BACKGROUND: Leishmaniasis, a chronic parasitic disease transmitted by Phlebotomus sandflies, affects millions of patients. Mucocutaneous leishmaniasis caused by Leishmania brasiliensis is endemic in much of South America. OBJECTIVE: Our purpose was to develop a system for staging mucocutaneous leishmaniasis on the basis of clinical, histopathologic, epidemiologic, and immunologic criteria. METHODS: Seventy-five Bolivian patients with mucocutaneous leishmaniasis were evaluated by history and physical examination; cutaneous, mucosal, and bone marrow biopsy specimens; and immunologic assessment. RESULTS: Mucocutaneous leishmaniasis may progress through three clinical stages: (1) the primary or cutaneous, (2) the cicatricial, and (3) the secondary or mucocutaneous stages. The primary stage can be further subdivided into three phases: lymphoplasmocytic, tuberculoid, and diffuse cutaneous phases. The secondary stage can also be subdivided into three phases: edematous, granulomatous proliferative, and granulomatous necrotizing stages. CONCLUSION: A classification or staging system enhances the ability to evaluate patients with mucocutaneous leishmaniasis and determine more accurately their prognosis and treatment. PMID- 8496457 TI - The clinical spectrum of mid-dermal elastolysis and the role of UV light in its pathogenesis. AB - BACKGROUND: We observed four patients with mid-dermal elastolysis (MDE) that was either precipitated or aggravated by UV light (UVL) exposure or was primarily confined to areas of UVL exposure. OBJECTIVE: Our purpose was to report four cases of MDE occurring after significant UVL exposure and to demonstrate why we suspect that MDE in some instances may be photoinduced or photoaggravated. We also wish to demonstrate the varied clinical presentation of this disorder. METHODS: Because all our patients had MDE involving skin exposed to UVL, biopsies were performed on clinically uninvolved sun-exposed and sun-protected skin in one patient to elucidate further the role of UVL in this process. RESULTS: On routine histopathologic examination we found that uninvolved sun-exposed skin but not sun protected skin demonstrated early MDE. Ultrastructural examination revealed a spectrum of elastic fiber changes in involved and clinically uninvolved sun exposed skin. Phagocytosis of elastic fibers was not present. CONCLUSION: We conclude that UVL exposure was a major causative or aggravating factor of MDE in our patients and that the clinical appearance of this disorder is variable. PMID- 8496458 TI - Natural history of the Naegeli-Franceschetti-Jadassohn syndrome and further delineation of its clinical manifestations. AB - BACKGROUND: The Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is rare; only three families have been reported. OBJECTIVE: Our purpose was to determine the natural history of this ectodermal dysplasia and to delineate further its clinical manifestations. METHODS: We reexamined the original family with the NFJ syndrome 65 years after the first description. RESULTS: The pedigree includes 62 members with 14 affected patients. We examined the 10 living patients. Longitudinal analysis of the pedigree revealed that the reticulate pigmentation fades after puberty and may disappear completely in old age. Hypohidrosis, the main problem for the patients, remains constant. Teeth are always severely affected, leading to early total loss. All patients lack dermatoglyphics. Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Four patients had congenital malalignment of the great toenails, not described previously in association with the NFJ syndrome. CONCLUSION: The NFJ syndrome is an ectodermal dysplasia with numerous specific abnormalities. PMID- 8496459 TI - Cutaneous changes of dermatomyositis in patients with normal muscle enzymes: dermatomyositis sine myositis? AB - BACKGROUND: Dermatomyositis sine myositis may have various connotations. Controversy exists as to nomenclature, degree of evaluation required, therapy, and course (e.g., does true dermatomyositis of the skin only exist?). OBJECTIVE: The purpose of this study was to assess prospectively patients with the clinicopathologic features of dermatomyositis and normal muscle enzyme serum levels to determine their course in terms of the onset of muscle disease. METHODS: Thirteen patients were studied by complete history and clinical examination, laboratory studies, electromyography, and skin and muscle biopsy. They were observed for 1 to 6 years. RESULTS: Patients were classifiable into three groups: (1) cutaneous changes only, (2) cutaneous changes only at baseline with subsequent development of myositis, and (3) cutaneous changes with normal muscle enzyme serum levels at baseline but with myositis demonstrated by electromyography and/or muscle biopsy specimens. CONCLUSION: Significantly different prognostic and therapeutic implications are present in patients with dermatomyositis with normal muscle enzyme serum levels depending on the results of electromyography, muscle biopsy, and clinical observation. PMID- 8496460 TI - Essential fatty acids in infantile seborrheic dermatitis. AB - BACKGROUND: In infantile seborrheic dermatitis (ISD) several different pathogenetic mechanisms have been proposed. OBJECTIVE: The purpose of the study was to investigate the importance of essential fatty acids (EFAs) and their metabolites in the origin of ISD. METHODS: The serum EFA patterns of 30 children with ISD, 1 to 6 months of age, were studied for 2 to 5 months. Blood samples were obtained at the time of diagnosis and after spontaneous recovery. Control samples were taken from age-matched healthy children. RESULTS: In children with active dermatitis levels of EFA 18:1w9 were increased and levels of 18:2w6 were decreased, whereas 20:4w6 levels remained normal. The rare fatty acid 20:2w6 was found in significant amounts in 20 patients, but at only barely detectable levels in the controls. All deviant values but the levels of 20:2w6 were normal at the time of recovery. Breast milk samples were obtained at the time of diagnosis from the patients' mothers and from a control group consisting of healthy nursing mothers. The EFA patterns were identical. The differences in EFA pattern between children with ISD and those free of skin disease were significant. The normalization of the deviation in ISD paralleled the recovery at any age it occurred. CONCLUSION: The laboratory findings suggest a transient impaired function of the enzyme delta-6-desaturase. The altered EFA pattern in ISD may be important in the pathogenesis of the disease. PMID- 8496461 TI - Fish scale-induced dermatitis. AB - BACKGROUND: Fish scales loosened during the process of cleaning that come in contact with human skin will adhere and "grow," creating a raised skin lesion if not washed off immediately. OBJECTIVE: The purpose of this study was to examine the process of fish scale-induced dermatitis. METHODS: Fish scales from the blue gill (Lepomis machrochirus) were placed on the intact skin of denuded Swiss Webster mice that had no prior sensitization. RESULTS: The scales physically adhered and formed a raised fold of skin within minutes after placement. Lesions were submitted for pathologic evaluation on days 2 and 7. A subacute irritant dermatitis was observed that evolved into a chronic dermatitis with hyperkeratosis. Inverted fish scales (the anatomically reversed surface) and fish epidermis did not produce such lesions on the mice. CONCLUSION: Fish scales are able to induce an irritant dermatitis. They most likely do so through initial adhesion via mucopolysaccharide secretions. PMID- 8496462 TI - Intralesional interferon-alpha and zidovudine in epidemic Kaposi's sarcoma. AB - BACKGROUND: Kaposi's sarcoma (KS) is the most common neoplasm in patients with acquired immunodeficiency syndrome (AIDS). To date, no therapy has proved to be consistently effective. OBJECTIVE: The purpose of this study was to evaluate the efficacy of intralesional interferon-alpha in patients with epidemic KS who were taking zidovudine. METHODS: Up to five lesions in each of 14 patients entered into the study were injected with 1 million U of interferon-alpha three times weekly for 6 weeks. Sterile water was used as a placebo control. The median zidovudine dose was 500 mg/day. The median CD4 count was 23/microliters. RESULTS: Of 14 patients evaluated, 13 of 14 (93%) showed a clinical complete response (CR) or partial response (PR) to therapy. Of 54 lesions injected, 41 (76%) showed a CR and 5 (9%) showed a PR, which resulted in an overall response rate of 85%. CONCLUSION: Intralesional interferon-alpha produced a high response rate in injected lesions of KS, but it failed to demonstrate superior efficacy over the placebo. PMID- 8496463 TI - An analysis of advertisements in the Journal of the American Academy of Dermatology, 1980 and 1990. PMID- 8496464 TI - Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. PMID- 8496465 TI - Adolescent self-mutilation in a rural area. PMID- 8496466 TI - Sex and drugs and nuclear war: secular, developmental and type A influences upon adolescents' fears of the nuclear threat, AIDS and drug addiction. AB - Researchers are divided over the significance of teenagers' expressed fear of nuclear war. This study of 3556 secondary school pupils examined whether (1) fear of nuclear war remains a feature of adolescent concern during the current east west detente; (2) the examination of responses in a large sample reveals age and sex differences in such expressed fears; (3) worry about 'real world' issues like nuclear war, AIDS and drug addiction relates more generally to Type A proneness in adolescents. The results suggest that fewer teenagers spontaneously raise fear of nuclear war than in previous "pre-Glasnost" research in Britain, that such concern is expressed differentially according to the child's age and sex and that secondary school pupils who express concern about nuclear war and AIDS are more likely to show significantly higher Type A identification. PMID- 8496467 TI - Sexual knowledge among Norwegian adolescents. AB - Sexual knowledge among Norwegian adolescents was studied. The data stemmed from a nationwide postal survey of 3000 Norwegian adolescents aged 17-19 years, yielding a response rate of 62.8%. Information on 16 sexual knowledge items was collected. The results showed considerable knowledge gaps among adolescents on sexual physiology and anatomy, sexually transmitted diseases, and fecundation/contraception. The level of sexual knowledge was higher among girls than boys, and increased with increasing age. Furthermore, sexual knowledge was positively associated with educational plans, frequency of discussing sex with friends, and experience of sexual intercourse. Sexual knowledge did not predict contraception use, when the effects of other independent variables were controlled for. The results of the study clearly demonstrate the need for further information and education efforts to increase sexual knowledge among adolescents. The potential adequacy of efforts which both activate and increase the quality of peer communication on sexual issues is addressed. PMID- 8496468 TI - Social support during adolescent pregnancy: a comparison of three ethnic groups. AB - This study compared similarities and differences in social support among black, Hispanic, and white pregnant adolescents and determined if support related to prenatal attachment. Participants (n = 161) completed Norbeck's Social Support Questionnaire (NSSQ), the Maternal Fetal-Attachment Scale and a background questionnaire. Black pregnant adolescents were found to have significantly lower total functional support scores (emotional and tangible support) than whites. A pattern of performance between ethnic groups was observed for all NSSQ social support variables, with whites obtaining the highest scores, followed by Hispanics and blacks. Although black adolescents identified the least number of individuals in their social network, the proportion of support provided by family was greatest for this ethnic group. The relationship between social support and prenatal attachment was not found to be significant. PMID- 8496469 TI - Psychological distress, work attitudes and intended year of leaving school. AB - Recent studies in both Australia and the U.K. have shown high levels of psychological distress and anxiety in secondary school pupils, increasing over the final three years of school. Indeed, the levels observed in final year pupils have been just as high as those observed in unemployed young people. It has been suggested that the discrepant findings in some longitudinal studies reported during the past few years might be due to the inappropriate use of at-school baseline measures, where disproportionate numbers of pupils at different levels could have affected the conclusions. In response to this suggestion data are reported from a longitudinal study of school leavers, in which 1980 at-school measures were analysed as a function of year level and intended year of leaving. The findings gave no support to the hypothesis that stress level increased from over the last three years, and therefore the use of baseline measures was vindicated. It was concluded that a decade of sustained high youth unemployment is the reason why those about to leave school seem prone to greater stress and anxiety than was the case ten years ago. PMID- 8496470 TI - Associated factors for self-reported binge eating among male and female adolescents. AB - As part of an epidemiological study, adolescents aged 12-19 (n = 3287) filled out a self-administered questionnaire concerning their eating behaviours. The analysis showed that binge eaters (BE) had disorderly eating habits (skipping meals, snacking, eating sweets, unbalanced diets), concern with body shape (feeling too fat) and depressive symptoms more often than non binge-eaters (NBE) did. This relationship between binging episodes on the one hand, and eating habits, concern with body shape, and depressiveness on the other, has been observed for both sexes, in separate logistic regression analyses. PMID- 8496471 TI - Overactivity and boundary setting in anorexia nervosa: an existential perspective. AB - Excessive motor activity in anorexia nervosa has been variously described as a symptom of a wider perceptual disorder, as the cause of anorexia, and as a neurologically based compulsive behavior. It is also considered a secondary symptom used to burn calories. In this paper, this symptom is considered from an existential perspective. It is first shown that the anorexic's mode of being is overly rational and not irrational as claimed by cognitive-behaviorists. It is then hypothesized that overactivity may help the anorexic person achieve a sense of existential permanence by dynamizing her static and too rational mode of being. It is also advanced that over-activity may play an adaptive role and should not be indiscriminately deterred in the treatment of anorexia nervosa. PMID- 8496472 TI - Differences two years after tooth extraction in mandibular bone reduction in patients treated with immediate overdentures or with immediate complete dentures. AB - In a randomized controlled clinical trial, 74 patients who required immediate dentures were randomly treated with immediate overdentures on two lower canines or with immediate complete dentures. Mandibular bone reduction was measured by use of oblique lateral cephalometric radiographs made at baseline and the results compared with those of one year and two years after denture treatment. Analysis of the data showed that the average bone reduction in the lower canine regions in the first year was 0.9 mm in the immediate-overdenture group and 1.8 mm in the immediate complete-denture group. In the posterior parts of the mandible, the bone reductions were, respectively, 0.7 mm and 1.9 mm. The differences were statistically significant in all measured regions. During the second year, no significant differences in bone reduction were found. The sums of differences in the first two years were significant in all regions except the molar region, preserving the initial difference. Retention of roots of canines beneath a mandibular denture in immediate denture patients, even when they were in poor condition, reduced the collapse of the alveolar processes in all regions of the mandible. PMID- 8496473 TI - Salivary yeasts, saliva, and oral mucosa in the elderly. AB - Yeasts are commensals in the oral cavity and may not cause disease unless there are predisposing host factors, such as other disease, or when medication is being taken. The elderly are at increased risk of yeast infection. In this paper, prevalence of salivary yeasts in a group of 368 inhabitants of Helsinki aged 76, 81, and 86 years is reported. Salivary yeasts were counted by the Oricult-N dip slide method, salivary secretion rate and buffering capacity were measured, type of dentition was noted, and signs of yeast infection and the occurrence of subjective symptoms were determined. There was no growth of yeasts in 25% of the subjects. From one to 20 colonies/slide were observed in 21%, 21-50 colonies in 21%, and over 50 colonies (a high count) in 33%. Subjects with low salivary flow rates and low buffering capacities had significantly higher yeast counts than did subjects with normal salivary flow rates and buffering capacities. High yeast counts were found in 19% of subjects with natural teeth. The corresponding percentages in those wearing partial or complete dentures were 32 and 41, respectively. High salivary yeast counts were associated with oral mucosal lesions but not with subjective complaints of oral symptoms. PMID- 8496474 TI - Adhesion of actinomyces isolates to experimental pellicles. AB - The ability of oral bacteria to adhere to surfaces is associated with their pathogenicity. Actinomyces can adhere to pellicle and cells through extracellular fimbriae. Research on adhesion of actinomyces has been conducted with use of hydroxyapatite (HA) coated with mammalian-derived salivary constituents, whereas the bacterial-derived components of the acquired pellicle have been largely ignored. The influence of the cell-free bacterial enzyme, glucosyltransferase (GTF), on adhesion of human and rodent isolates of Actinomyces viscosus was examined. Cell-free GTF was adsorbed onto parotid saliva-coated hydroxyapatite (sHA). Next, A. viscosus was exposed to the pellicle following the synthesis of glucan formed in situ by GTF. Glucans formed on the pellicle served as binding sites for adhesion of a rodent strain of A. viscosus. Conversely, the presence of in situ glucans on sHA reduced the adhesion of human isolates of A. viscosus compared with their adhesion to sHA. Adhesion of the rodent strains may be facilitated through a dextran-binding protein, since the rodent strains aggregated in the presence of dextrans and mutan. The human isolates were not aggregated by dextran or mutan. Pellicle harboring A. viscosus rodent strains interfered with the subsequent adhesion of Streptococcus mutans to the bacterial coated pellicle. In contrast, the adhesion of S. mutans to pellicle was not decreased when the pellicle was pre-exposed to a human isolate of A. viscosus. The experimental data suggest that human and the rodent isolates of A. viscosus have distinct glucan adhesion properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496475 TI - Calcification of a cariogenic Streptococcus and of Corynebacterium (Bacterionema) matruchotii. AB - The main aim of this investigation was to challenge the idea that cariogenic streptococci do not calcify. Calcium uptake of calcification of Streptococcus mutans C180-2, proven to be an acidogenic and cariogenic strain, was compared with calcium uptake and calcification of Corynebacterium (Bacterionema) matruchotii, known as a ready calcifier. Bacteria were grown on Brain Heart Infusion Agar (BHIA) and on well-buffered semi-synthetic E-agar, both containing 1.4 mmol/L calcium, 2 g/L glucose, initial pH 7.4. Calcium uptake from BHIA by C. matruchotii (25 mmol Ca/kg wet bacterial cell mass), but not by S. mutans, was found. Grown as a plaque-like lawn on E-agar, the S. mutans cell mass concentrated calcium to 63 +/- 11 mmol/kg compared with 145 +/- 61 mmol/kg in C. matruchotii. X-ray diffraction confirmed the presence of crystalline apatite in the bacterial cell masses. Electron microscopy revealed crystals and mineralized deposits in both organisms. Heavy calcifications in some cells of S. mutans were seen. Calcification was partly inhibited by magnesium ion and by methanehydroxybisphosphonate. S. sobrinus 6715, as well as freshly isolated S. mutans and S. sobrinus from patients, concentrated very large quantities of calcium, up to 500-fold from the medium, when maintained for several weeks on E agar of initial pH 7.6. Our observations widen the view on acidogenic bacteria as mineralization agents and support the notion that members of the mutans group of streptococci may be involved in events that trigger heavy intracellular calcifications and, possibly, dental calculus formation. PMID- 8496476 TI - Transformation efficiency of EMS-induced mutants of Streptococcus mutans of altered cell shape. AB - Some Streptococcus mutans strains change shape from bacillary to coccal or ellipsoid form in response to the ratio of bicarbonate to potassium or of borate to potassium in growth media. So that insight into determinants of shape of these streptococci could be gained, and future genetic studies facilitated, the shapes of a series of transformable and nontransformable strains of S. mutans were studied and attempts made to isolate a mutant of augmented transformability. Several strains were mutagenized by ethylmethane sulfonate and mutants with altered colonial and cellular morphologies isolated. Cell shapes were studied by Gram stain and Nomarski interference microscopy, and by scanning and transmission electron microscopy. Diverse shape-altered mutants were isolated from seven transformable and two nontransformable strains of S. mutans. Among these, length to-width ratios ranged from > 10 to about 0.25. Regulation of timing of cell division, septum formation, or septum completion events may have been altered in these mutants. While most mutants substantially or completely lost transformability, mutant LT11 had transformation efficiency of 1.3 x 10(-4) to 2.3 x 10(-3), more than two to three orders of magnitude greater than its parental UA159 and the well-known transformable strain GS5(HK), respectively. There was no evidence of production of competence factor by LT11. Competence of LT11 was maintained for at least six months upon storage at -70 degrees C, facilitating its use for genetic studies. While the morphologies of several shape altered mutants were no longer responsive to changes of the bicarbonate/potassium, unlike those of their parentals, the morphology of LT11 persisted in its response to this condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496477 TI - Molar efficiency study of chlorinated NPG substitutes in dentin bonding. AB - This study evaluated and compared the contributions to dentin adhesive bonding of three N-phenylglycine analogues with electron-withdrawing substituents on the aromatic ring. These electron-deficient "N-compounds" included: N-(4 chlorophenyl)-glycine (NCPG), N-methyl-N-(4-chlorophenyl)-glycine (NMNCPG), and N (3,4-dichlorophenyl)-glycine (NDCPG). An experimental three-step dentin-bonding protocol that consisted of sequential application of acidic ferric oxalate solution, an N-compound in acetone, and a surface-active comonomer in acetone was used. The first and third steps were held constant throughout the study. Each N compound (NCPG, NMNCPG, NDCPG) was used in step two at ten concentrations ranging from 0.0 mol/L (pure acetone) to 5 x 10(-1) mol/L, depending on solubility. After overnight storage in distilled water, the dentin-to-composite bonds were broken in tension. The data were analyzed with ANOVA, and multiple comparisons were performed with Duncan's Multiple Range test. All statistical tests were controlled at alpha = 0.05. At 5 x 10(-3) mol/L, the relative effectiveness of the three N-compounds (as measured by tensile bond strengths) was NMNCPG > NCPG > NDCPG. Of all concentrations studied, the mean bond strengths produced with NMNCPG were statistically as good as or better than those produced by the other two compounds, and NCPG was always as good as or better than NDCPG. Increased electron-withdrawing from the nitrogen of the amine group by the substituents narrowed the effective concentration range for dentin bonding and, in general, produced lower mean bond strengths between dentin and composite. PMID- 8496478 TI - Women in dental research: predictions for the future. PMID- 8496479 TI - Closest speaking space during the production of sibilant sounds and its value in establishing the vertical dimension of occlusion. AB - The purpose of this investigation was to determine whether the production of sibilant sounds involved adopting a jaw position that corresponded to the closest vertical speaking space (CSS), by analysis of the smallest vertical excursion of the mandible during the performance of different phonetic exercises. A further objective was to establish the variability in the CSS produced by individual sibilant phonemes. Thirty young adult subjects had their CSS determined during three separate phonetic tests, using a kinesiograph (Sirognathograph, Siemens A.G., Benshiem, Germany) and a Bio-Pak (BioResearch Associates Inc., Milwaukee, WI) jaw-tracking software program. The first test was a general phonetic articulation test containing all the sounds of the English language and specifically including all six sibilant word sounds. The second phonetic test contained the six sibilant sound making up a short sentence. The third test included six single words, each expressing a different sibilant sound. No statistically significant difference among the mean CSS determined in each of three exercises was demonstrable. A phonetic test containing all sibilant sounds produced a CSS equivalent to that of a test containing all speech sounds. The vertical component of the CSS was also independent of the form or duration of the phonetic tests containing the sibilant word sounds used in this investigation. The CSS determined for 5 of the individual sibilant phonemes in the third exercise differed (p < 0.05) from that calculated for the three complete exercises. It was concluded that voicing sibilant phonemes, or word sounds, does cause the subject to adopt the CSS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496480 TI - A multiple logistic regression analysis of the risk and relative odds of temporomandibular disorders as a function of common occlusal features. AB - A multiple logistic regression analysis was used to compute the odds ratios for 11 common occlusal features for asymptomatic controls (n = 147) vs. five temporomandibular disorder groups: Disc Displacement with Reduction (n = 81), Disc Displacement without Reduction (n = 48), Osteoarthrosis with Disc Displacement History (n = 75), Primary Osteoarthrosis (n = 85), and Myalgia Only (n = 124). Features that did not contribute included: retruded contact position (RCP) to intercuspal position (ICP) occlusal slides < or = 2 mm, slide asymmetry, unilateral RCP contacts, deep overbite, minimal overjet, dental midline discrepancies, < or = 4 missing teeth, and maxillo-mandibular first molar relationship or cross-arch asymmetry. Groupings of a minimum of two to at most five occlusal variables contributed to the TMD patient groups. Significant increases in risk occurred selectively with anterior open bite (p < 0.01), unilateral maxillary lingual crossbite (p < 0.05 to p < 0.01), overjets > 6-7 mm (p < 0.05 to p < 0.01), > or > 5-6 missing posterior teeth (p < 0.05 to p < 0.01), and RCP-ICP slides > 2 mm (p < 0.05 to p < 0.01). While the contribution of occlusion to the disease groups was not zero, most of the variation in each disease population was not explained by occlusal parameters. Thus, occlusion cannot be considered the unique or dominant factor in defining TMD populations. Certain features such as anterior open bite in osteoarthrosis patients were considered to be a consequence of rather than etiological factors for the disorder. PMID- 8496481 TI - Effects of oral sensory afferents on mastication in the miniature pig. AB - The performance of mastication is presumed to be influenced by afferent stimulation, but little information is available from awake, intact animals. Thirteen experiments were carried out with four miniature pigs. Electromyographic signals from the jaw muscles were recorded simultaneously with jaw movements during natural chewing of foods of differing hardnesses. Harder foods were found to be associated with higher activity levels of jaw-closing muscles and greater lateral deviation, but reduced jaw opening. The sensory supply from one side of the oral cavity was then removed by injected local anesthetic, and the recordings repeated. In addition to decreased activity levels, the jaw-closing muscles showed reduced ability to adjust to different foods. The frequency of mastication fell slightly, and the animals preferred to chew on the uninjected side. Lateral deviation was reduced, but at the same time the jaw-opening muscles usually became more active and accordingly the jaw opened more widely. These findings provide new information on the role of oral sensory afferents in regulating natural chewing patterns. The decreased activities of the jaw-closing muscles are consistent with, although they do not demonstrate, the existence of a positive feedback from periodontal afferents. PMID- 8496482 TI - Neural changes in periapical lesions after systemic steroids in the ferret. AB - This study was intended to clarify the relationship between the neural changes which occur around the apex of the ferret canine after pulpectomy and the inflammatory process induced by the procedure. In 12 young adult ferrets, under general anesthesia, the pulps in the mandibular canine teeth were removed and replaced with gutta percha and Grossman's sealer. Six of the animals were treated with dexamethasone to reduce the inflammatory response. Three months later, the animals, again under general anesthesia, were perfused with a fixative mixture. Three unoperated animals that had not been treated with dexamethasone were also perfused. The mandibular canine teeth and their supporting tissues were removed, processed, and serially sectioned. Three-dimensional reconstructions of the periapical lesions in each animal were assembled and their volumes measured. The density of innervation in the periapical region was estimated. The mean lesion volume in the pulpectomized animals not treated with dexamethasone was 3.54 (+/- 2.27) mm3 and in the dexamethasone-treated animals 1.33 (+/- 1.31) mm3. The differences were statistically significant when tested by the Mann-Whitney U test (p < 0.01). Bacteria were not seen within any of the lesions. The innervation density beneath the canines in the pulpectomized animals not treated with dexamethasone was 164 units per mm2 (+/- 80) and in the steroid-treated animals 151 +/- 68 units per mm2. In the control, untreated animals, the innervation density was 22 +/- 10 units per mm2. The difference between the steroid-treated pulpectomized animals and the untreated pulpectomized animals was not statistically significant (p > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496483 TI - A wolf in sheep's clothing. PMID- 8496484 TI - Clinical misdiagnosis of squamous cell carcinoma in situ as seborrheic keratosis. A prospective study. AB - BACKGROUND: Seborrheic keratoses have on rare occasion been reported to undergo malignant transformation. OBJECTIVE: Our purpose was to examine the incidence and distribution of squamous cell carcinomas (SCCs) in situ arising in clinically banal-appearing seborrheic keratoses. METHODS: We prospectively selected such cases over a 6-month period of time from routinely accessioned specimens to a dermatopathology service. RESULTS: We found 1.4% of clinically diagnosed seborrheic keratoses to be SCCs in situ. These lesions were more common in elderly persons and were more likely to occur on the head and neck, suggesting the role of cumulative sun damage in the transformation of such lesions. CONCLUSION: Malignant transformation of seborrheic keratoses, although rare, appears to occur more frequently in the elderly on the head and neck. Because this change is not necessarily accompanied by clinically discernable changes, more careful scrutiny of such lesions may be of therapeutic rather than cosmetic significance in this population. PMID- 8496485 TI - A three-step systematic incisional-slit minigrafting approach. AB - BACKGROUND. Over the past decade, minigrafting has become the cornerstone of effective hair transplantation because the "corn row" appearance commonly seen with larger grafts occurs frequently with smaller grafts. However, there still has not appeared in the literature a sequential, systematic approach that yields consistently good results. This article offers an organized blueprint that not only has given predictable and excellent results, but has expedited the minigraft procedure. OBJECTIVE. To present a three-step incisional-slit minigrafting approach. RESULTS. The method described gives excellent aesthetic results and expedites the procedure. PMID- 8496486 TI - Melanoma update. Second primary melanoma. AB - BACKGROUND: Second primary melanoma is not a rare phenomenon. It occurs in at least 3 to 6% of melanoma patients and up to a third of individuals from melanoma prone families. OBJECTIVE: To review the clinical and histologic features of multiple primary melanoma. A schema for follow-up of these patients is presented. CONCLUSIONS: As the incidence of melanoma continues to rise, we will be faced with an ever increasing number of patients who have survived their tumor. These patients are at risk for subsequent melanomas. This article reviews the literature regarding multiple primary melanoma, and discusses patient management. PMID- 8496487 TI - The immunogenicity of bovine collagen implants. PMID- 8496488 TI - Stasis papillomatosis. Clinical features, etiopathogenesis and radiological findings. AB - Stasis papillomatosis can be divided into localized and widespread forms. Ten patients with this disease are discussed with emphasis on their clinical and lymphoradiological findings. Using isotope lymphography we were able to find an overall lymphostasis in only four patients. In all patients, local lymphatic disturbances were detected by means of indirect lymphography with intradermal lymph cysts as the most specific sign. Local dermal lymphostasis seems to be the common final pathogenesis in spite of different etiologies (ie, primary lymphedema, chronic venous insufficiency, trauma recurrent erysipelas, and local lymphangiodysplasia of unknown origin). A maximum variant was seen, following en bloc resection of subcutaneous tissue in a patient suffering from congenital lymphedema. PMID- 8496489 TI - A microbiologic study of diluted sclerotherapy solutions. AB - BACKGROUND: As sclerotherapy has become more of an exact science it has become appropriate to dilute various sclerosing solutions to produce the least concentration of sclerosant producing effective endosclerosis of a given vessel diameter--the minimal sclerosant concentration. OBJECTIVE: In this setting it has become necessary to take into account various microbiologic considerations. Contamination of infusates is the most common cause of epidemic device-related bloodstream infections. With these considerations in mind, the following study was undertaken to determine the bacterial and fungal content of varied concentrations of four commonly employed sclerotherapy agents. METHODS: Dilutions were made of hypertonic saline 23.4% to 11.7% with both bacteriostatic water and 0.9% normal saline, Polidocanol 0.5% to 0.25% with bacteriostatic water, sodium tetradecyl sulfate 1.0% to 0.5% with bacteriostatic water, and polyiodide iodide 2% to 1% with bacteriostatic water under sterile conditions. Each sclerosant was analyzed for bacterial, fungal, and spore content at determined time intervals with standardized utilization indices for up to 3 months. RESULTS: At each sclerosant concentration for sodium chloride, polidocanol, sodium tetradechol sulfate, and polyiodide iodide at each study design time interval for sampling all bacterial and fungal cultures remained sterile. CONCLUSIONS: With appropriate aseptic techniques we may dilute sclerosing solutions to desired concentrations that will remain sterile for a period of at least 3 months under daily usage conditions. PMID- 8496490 TI - Stab avulsion of the short saphenous vein. Technique and duplex evaluation. AB - BACKGROUND: Stab avulsion, largely employed for removal of superficial collateral varicosities, is generally considered unsuited for surgical removal of the varicose short saphenous vein. OBJECTIVE: To describe the technique of stab avulsion of the short saphenous vein and objectively validate it by demonstrating the exact site of short saphenous vein division in the popliteal fossa. METHODS: Postoperative duplex scan of popliteal fossa in 18 limbs, 3.5 months after stab avulsion of the short saphenous vein. RESULTS: No short saphenous vein stump in 4 limbs (22%). An average 1.7-cm (range 1 to 4 cm) stump in the remaining 14 limbs. CONCLUSIONS: High (not flush) ligation of the standard short saphenous vein, considered adequate by experts who practice traditional (open field) surgery, can also be achieved by stab avulsion without a large incision, and dissection in the popliteal fossa. The stab avulsion technique is therefore adequate for removal of the standard short saphenous vein. However, because of the short-term follow-up of this study, in which cases high ligation is as efficacious as flush ligation cannot be indicated. PMID- 8496491 TI - A vein has a preferential axis of flattening. AB - BACKGROUND: A vein is a collapsible tube. As such, has it one or several axes of flattening? OBJECTIVE: The objective is to demonstrate that several venous parts, like valves or orifices of tributary veins, are directed towards one axis. METHODS: With dynamic endoscopies for superficial veins and with anatomical injections of latex for deep veins. RESULTS: All the valvular free borders of the superficial veins are parallel to the skin's surface, all the terminal orifices of the perforator are really situated on the commissure linear (linear joining two superposed valvular commissures) of the deep veins. CONCLUSION: A vein has a preferential axis of flattening, and its cross-section configuration can be defined as: two wallsides and two borders. The bicuspid valve's cornua are situated on the borders of the vein. The terminal orifices of the perforators are situated on the borders of the deep veins. The models of the musculovenous pump of the calf have to be altered. PMID- 8496492 TI - Lichen myxedematosus treated with chlorambucil. AB - BACKGROUND: Chemotherapy with various alkylating agents has been reported to be successful in the treatment of lichen myxedematosus. However, serious toxicities have accompanied such use. OBJECTIVE: To report a case of treatment of lichen myxedematosus with chlorambucil. RESULT: There was a favorable response using chlorambucil as an alternative therapeutic agent. PMID- 8496493 TI - Mucoepidermoid carcinoma of the lip. PMID- 8496494 TI - Solitary mastocytoma in an adult. Treatment by excision. AB - BACKGROUND: In approximately 65% of patients, mastocytosis presents between birth and 15 years of age. Although solitary mastocytomas usually appear within the first 3 months of life, in unusual circumstances they may appear in adulthood. OBJECTIVE: The rare entity of solitary mastocytoma in adulthood and the simple treatment method of excision are discussed. METHODS: Simple surgical excision without manipulation of the lesion was performed. RESULTS: The lesion was surgically excised without recurrence. CONCLUSION: Solitary mastocytoma is a rare lesion in adulthood. The differential diagnosis includes a melanocytic nevus, xanthogranuloma and leukemia cutis. Surgical excision offers a rapid, relatively simple and effective mode of treatment. PMID- 8496495 TI - CO2 laser blepharoplasty. PMID- 8496496 TI - Preserving nurse caring in a destitute time. PMID- 8496497 TI - The experience of in vitro fertilization and gamete intra-fallopian transfer. AB - Research was conducted using qualitative techniques, in order to bridge the gap between radical feminist perspectives on in vitro fertilization programmes, which are usually theoretical in nature, and quantitative research which considers the experiences of women and couples involved in these programmes. Semi-focused interviews were carried out with 10 women who were currently undergoing, or had recently undergone, in vitro fertilization or gamete intra-fallopian transfer, in order to explore the experiences and the emotions associated with participation in these programmes. By utilizing a woman-centred approach, a richness of experiential data was obtained, which would not have been achievable by quantitative means, and yet the women involved were able to retain some control over the research process. PMID- 8496498 TI - Growth versus stability: older primiparous women as a paradigmatic case for persistence. AB - The early pregnancy experience of women over 30 offers paradigmatic evidence which supports the significance of persistence for the study of nursing phenomenon. Pregnancy and first-time motherhood have come to be associated with change, growth and development. This research, which was undertaken to describe the changes experienced by older primiparous women during early pregnancy, illustrates how research grounded in a particular paradigm, in this case the growth or developmental paradigm, can limit the interpretation of data. When viewed from a developmental perspective, women in this sample were seen as resistant to change and could be said to be having trouble 'adapting' to their impending motherhood. However, when these women were viewed from the perspective of stability they were seen to engage in activities that allowed them to persist in their current self-view. In the biological sciences, persistence refers to a compensatory process which allows a system to maintain goal-directedness in spite of both internal and external disturbances. Women in this sample used balancing and buffering to continue their self-patterns. Balancing represented the verbal and behavioural processes women engaged in to integrate their experience of themselves as pregnant into their sense of themselves as not pregnant. Buffering included those activities that women used to maintain a sense of themselves in the face of the threat posed by their impending motherhood. Balancing and buffering represent mechanisms used in the service of persistence and reflect pattern maintenance activities. PMID- 8496499 TI - The genesis of a phenomenological approach to advanced nursing practice. AB - This paper describes how participation, as a co-investigator, in a phenomenological study of the high-risk perinatal experience led to the development of a new approach to advanced nursing practice for a maternity clinical nurse specialist. Prior to implementation of the study, nursing was practised based in a structured, conceptual framework, but, as a result of conducting interviews with study subjects, analysing data with a research team and gaining a better understanding of the high-risk perinatal experience, a new style of nursing practice based in a phenomenological approach emerged, which permeated all aspects of clinical nurse specialist practice. PMID- 8496500 TI - Specialist or generic community nursing care for HIV/AIDS patients? AB - Improved management of HIV-related illness means that patients spend over 80% of their time in non-institutional settings. Most community-based health care in the United Kingdom is provided by primary health care teams: general practitioners and community nurses, with support from social workers. However, in many areas specialist HIV services have assumed responsibility for the care of HIV/AIDS patients, and primary health care teams have only played a marginal role. Our study examined patterns of community nursing for HIV/AIDS patients in one regional health authority, North-East Thames (NETRHA). Interviews with 77 people in seven health districts included community nurse managers, clinical nurse specialists (CNS) HIV/AIDS and palliative care nurses. The appropriateness of different nursing models was assessed, taking into account the changing epidemiological and demographic profile of the disease, the influence of dedicated HIV funding, and the effect of recent British National Health Service reforms. Three models of care have developed in NETRHA: specialist HIV teams, individual CNS HIV/AIDS acting as a resource to generic staff, and care given by generic community nurses. Our work suggests that both generic community nurses and patients benefit from specialist input, and that this should be provided using CNSs HIV/AIDS in an advisory and facilitative capacity. PMID- 8496501 TI - Hope in the family caregiver of terminally ill people. AB - This longitudinal study explored the meaning of hope, the influence of specific background characteristics on hope, and identified strategies that are used to foster hope in a convenience sample of 25 family caregivers of terminally ill family members from two hospice programmes using the technique of methodological triangulation (interview, Herth Hope Index and Background Data Form). Hope was defined as a dynamic inner power that enables transcendence of the present situation and fosters a positive new awareness of being. Six hope-fostering categories and three hope-hindering categories were identified based on the interview responses. With the exception of those providing care to a family member diagnosed with AIDS and those caregivers experiencing poor personal health, a high fatigue level, severe sleep deprivation and more than two concurrent losses, overall hope levels among participants were found to remain stable across the background variables. Across time, hope levels were found to be low at interview time one, rise significantly by time two and then level off for the remainder of the time. An understanding of hope from the perspective of the family caregiver could provide a basis upon which to develop interventions that foster hope. PMID- 8496502 TI - The search for meanings in nursing: could Facet Theory be a way forward? AB - This paper examines some of the underlying tenets of Benner & Wrubel's Primacy of Caring, and suggests the use of Facet Theory as a possible route to overcome criticisms of the lack of systematic data collection and analysis in this approach to nursing research. Some of the steps undertaken in Facet Theory are described, and its use in wider nursing research discussed. It is proposed that Facet Theory offers a method of studying the multidimensional nature of nursing, which has the potential for a scientific approach without losing the essential ontological data. PMID- 8496503 TI - A critique of Fawcett's 'Conceptual models and nursing practice: the reciprocal relationship'. AB - This paper offers a critique of Fawcett's paper 'Conceptual models and nursing practice: the reciprocal relationship' published in 1992, in which it is argued that 'conceptual models inform and transform nursing practice by informing and transforming the way in which nursing is experienced and understood, and that nursing practice informs and transforms conceptual models by informing and transforming the content of the conceptual model'. The critique begins by locating Fawcett's view of the relationship of nursing models to nursing practice within the intellectual tradition of positivism. For the purposes of the critique, Fawcett's positivism is not taken as being problematic in itself; however, it is argued that the standards of evidence upon which some of her arguments are based are not compatible with the practice of positivist social science, with the result that the paper is internally inconsistent. In particular, Fawcett's suggestion that nursing models are validated as evidence accumulates in their favour is contrasted with Popper's view that the validity of theoretical statements is established as they withstand attempts to demonstrate their falsity; and Fawcett's belief that nursing models are models in the scientific sense, which can be inferred from her adoption of the terminology of Kuhnian epistemology, is not found to be justified. If, for the positivist, the validity of practice is directly proportional to the validity of the theory upon which it is based, then nursing models which lack 'scientific' validity cannot be regarded as a proper basis for nursing practice. Finally, Fawcett has been criticized for failing to produce evidence of any kind to demonstrate that nursing models have a beneficial effect upon nursing outcomes. PMID- 8496504 TI - Long-term care patients and their dietary intake related to eating ability and nutritional needs: nursing staff interventions. AB - Meals combine human beings' nutritional requirements with cultural needs. The aim of this paper was to evaluate how individual patients' meals were planned, carried out and followed up by nursing staff related to nutritional requirements and ability to eat in the ward. Eighteen newly admitted long-term care patients hospitalized for more than 3 weeks were observed for up to 6 weeks. The patients' conditions were examined using interviews, observations, recorded data and analyses for nutritional assessment. Fourteen patients experienced difficulties related to motor dysfunctions in the upper extremities, mouth and pharynx in handling food. Six of those were prescribed feeding aids or nutritional supplement. Biochemistry was not used as a basis for these interventions and four at risk of malnutrition on admittance were missed. Thus, this study exposed defective nursing assessment strategies. However, eating dependency was prevented and nutritional status tended to recover among those where interventions were made. PMID- 8496505 TI - Managing the early discharge experience: taking control. AB - The purpose of this study was to understand women's experiences in an early discharge programme. Using grounded theory, the investigator collected, coded, compared and contrasted data gathered in unstructured interviews with eight women. The women managed their early discharge experience, first, by taking control of their antenatal and intrapartal care once they were accepted into the programme and, later, by taking control of their postpartum recovery and their infants' care. Taking control was influenced by the women's beliefs about family and home; their personalities, e.g. their ability to accept help; and their available support. Their beliefs, personalities and available support were central to their motivation to participate in the early discharge programme and to their perception of a successful experience. The women used a number of strategies to take control. These strategies emerged during organizing antepartal requirements, meeting their own expectations during labour and birth, and learning to trust their abilities to manage self-care and parenting postpartum. The women anticipated their increased family involvement, family integration and participation in decision-making. They did not, however, anticipate their increased feelings of confidence and competence. Taking control has implications for health professionals who are working with childbearing women experiencing early discharge. PMID- 8496506 TI - Training in psychosocial intervention: the impact on the role of community psychiatric nurses. AB - A group of community psychiatric nurses (CPNs) received training via a short part time course to deliver psychosocial intervention (PI) to families caring for a relative with schizophrenia living at home. The effects on CPNs of training in PI were examined by measuring, over time, a number of variables which reflected; CPNs' attitudes to schizophrenia, their skills, specific aspects of their role (such as visit length and frequency, caseload composition, etc.), and relationships with other disciplines. Analysis of the information showed that CPNs trained in PI changed their attitude to schizophrenia very little. However, evidence was obtained that CPNs' attitudes moved towards behaviour therapy as a preferred treatment approach. All CPNs who received training were competent in the component and global skills of PI at the end of training. These scores derived from blindly rated audiotaped recordings of CPN intervention. The CPNs estimated that caseload size and the proportion of people on caseloads with a diagnosis of schizophrenia did not alter. However, significant increases in the length of CPN sessions with people with schizophrenia and their families were observed. The CPN's liaison role with consumer groups, such as the National Schizophrenia Fellowship, significantly improved. Multi-disciplinary colleagues gave PI-trained CPNs a mixed reaction. Some CPN colleagues seemed pleased to transfer families to the PI-trained CPNs' caseloads, whilst others clearly regarded the PI-trained CPNs as a threat. Overall, the most encouraging reaction came from psychologists and psychiatrists. PMID- 8496507 TI - Occupational stress in psychiatric nursing. AB - Psychiatric nursing is invariably assumed to be a stressful area of nursing practice. Empirical evidence to support this proposition is limited, however, due to the lack of research in this field. The purpose of this project was to examine occupational stress in a specified area of psychiatric nursing. The research was exploratory and therefore the concern was discovery and description rather than the testing of clear hypotheses and the development of causal relationships. The study has four main objectives. First, to describe the various stressors present in the work of the psychiatric nurse in the acute admission wards of two district health authorities. Secondly, to measure the effects of stress using a recognized and well-validated instrument for recording levels of burnout. Thirdly, through the use of a particular theoretical framework to identify the types of coping strategy used by the participants in the study. Fourthly, to note any clear associations between the stressors, the effects of stress and the ways of coping identified in the study. The conceptual basis for the project was Lazarus's cognitive theory of stress and coping and Maslach's model of burnout. PMID- 8496508 TI - Transcultural nursing: a selective review of the literature, 1985-1991. AB - This paper reviews selected work, published in nursing journals between 1985 and 1991, on the subject of transcultural nursing. The papers were selected by the use of a computerized literature search at the Royal College of Nursing library, using the keywords transcultural, multicultural, crosscultural and cultural. The benefits and limitations of such an approach will be discussed along with an introduction to transcultural nursing. The journal papers were then reviewed under eight headings, theory and concepts, nurse education, health education and patient teaching, clinical, counselling, sexuality, care of the child and research. Common themes and problems are discussed. PMID- 8496509 TI - Acting at a disaster site: views expressed by Swedish nursing students. AB - There is a common interest in Swedish society in preparing nurses well for disasters. A special course in the basic nurse education programme is devoted to disaster nursing. The aim of this study is to investigate nursing students' knowledge and views of their own action at the disaster site, both in their professional role and as private persons. The present study is a descriptive one based on the students' written answers. The result shows that the students emphasize contacting the overall disaster officer, surveying the situation and carrying out basic life-saving measures in Sweden known as the ABCs. They also stress the importance of staying calm and, to a lesser extent, seeing to the needs of the mentally shocked. Thus the nursing students seem to regard treatment of physical injuries as most important in the disaster situation. PMID- 8496510 TI - Caring perspectives in nursing education: liberation, transformation and meaning. AB - The author's personal journey through many years of nursing education as both a student and faculty member lead to a theoretical exploration of a caring pedagogy between students and teachers. The author places this exploration in a historical context and examines education, feminist and nursing literature to evolve common themes in describing caring pedagogy within nursing. Finally, the author suggests a model that forms the foundation for nursing curricula based on caring values. PMID- 8496511 TI - Clinical role modelling: uncovering hidden knowledge. AB - Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team. PMID- 8496512 TI - Evaluation of the efficacy of an instructional programme in the self-management of patients with asthma. AB - The restrictions imposed on patients with asthma is problematic to them, in that their physical disability interferes with personal, interpersonal and/or professional goals. Twenty-three patients under the care of general practitioners were surveyed by interview in their homes, doctors' surgery or at work to determine their current control of selected variables related to their asthma: exercise, use of drugs and related factors. An instructional programme was offered to interested participants to assist in complying with their prescribed medication regimens and to tailor exercise to their tolerance levels. Findings showed that 18 patients experienced moderate to severe restrictions when troubled with asthma. Although over one-half of the patients exercised regularly for fitness, including seven with aerobic exercise, some chose sports they thought could provoke an asthmatic attack. Half took precautionary measures when exercising. All patients used bronchodilators to relieve their asthma, yet one third did not keep their inhalers accessible. None of the most troubled 18 lived in a smoke-free environment, and one-third kept furry animals as pets. Recommendations are made for further study of the effects of instructional programme to improve compliance to a healthy lifestyle. PMID- 8496513 TI - An investigation into whether nurses change their learning style according to subject area studied. AB - The aim of this study was to investigate whether nurses' preferred learning styles varied according to subject area studied. Thirty nurses in a postgraduate centre specializing in cardiothoracic care were interviewed using a semi structured technique. The results suggest that there is a change in learning style as different subjects are studied. Other factors emerging were the importance of previous learning experience, the wish to share, to be acknowledged and the need for close links between theory and practice. This calls for nurse teachers to examine their practice, to update and undertake professional development and also to establish close clinical links. PMID- 8496514 TI - Peer teaching among nursing students in the clinical area: effects on student learning. AB - Substantial use of clinical peer teaching among students has been reported, but there is limited description of outcomes and no reports of the use of a theoretical framework. The purpose of this study was to investigate the effects of peer teaching on baccalaureate nursing students' clinical performance. It was hypothesized that students who were taught by peers will: (a) achieve significantly higher improvement scores than students taught by teachers alone; and (b) rate their preference for peer teaching equal to or higher than instructor teaching. Bandura's (1971) social learning theory provided the framework for the study. The experimental design involved 50 volunteer subjects on two surgical units, one for peer teaching and one for instructor teaching. Data were collected from pre- and post-psychomotor and cognitive tests of a surgical dressing procedure and from a Clinical Teaching Preference Questionnaire (CTPQ). Experimental subjects achieved significantly higher cognitive improvement scores (t = 1.67; P < 0.05) and moderately higher psychomotor improvement scores in support of hypothesis 1. Responses on the CTPQ showed support for hypothesis 2. PMID- 8496515 TI - Development and testing of the autobiographical memory coding tool. AB - Development and testing of the autobiographical memory coding tool (AMCT) is detailed. The tool uses quantitative content analysis procedures to code interpretations of autobiographical memories as validating or lamenting. Development of a system of measuring autobiographical memories from transcribed reminiscence interviews involved defining the units of analysis, defining the categories and themes, constructing a codebook, assessing content validity, assessing reliability and making revisions. Thirty-nine transcripts of reminiscence interviews were used for tool development and testing. The AMCT contains a series of step-by-step guidelines for conducting the analysis and includes an autobiographical memory thematic dictionary and descriptions of range and variations in each theme to assist with coding data. Intercoder reliability estimates were 0.93, 0.93 and 0.95. Test-retest reliability was 1.00. PMID- 8496516 TI - Leading with charisma. AB - Traditionally, leaders have used characteristics related to authority, control, competition and logic. Such approaches are more autocratic, and task-oriented. With changes in society, employers are focusing less on tasks and more on job satisfaction. Leaders are focusing on co-operation versus competition. Human relations and recognition are being used as motivators. Charisma is an important characteristic for leaders who wish to motivate by interpersonal characteristics. Transformational leadership is an emerging paradigm for modern management and can be important to the modern nurse manager as well. This paper describes charisma and how it can be useful to the nurse manager. PMID- 8496517 TI - Balloon angioplasty for the treatment of lesions in saphenous vein bypass grafts. AB - OBJECTIVES: The purpose of this review is to assess the value and limitations of balloon angioplasty for the treatment of saphenous vein bypass graft obstructions. The potential efficacy of new interventional techniques is discussed. BACKGROUND: Treatment of ischemia due to saphenous vein bypass graft obstructions poses a difficult problem that will be encountered more often as the pool of surgically treated patients continues to accumulate. Reoperation is technically demanding and is associated with high mortality and morbidity rates. Balloon angioplasty may provide a suitable alternative. METHODS: The review proposes a classification of patients with attempted saphenous vein graft angioplasty according to expected early and late outcome based on the data obtained from the relevant published data and personal experience. RESULTS: Angioplasty of a nonocclusive obstruction in a saphenous vein bypass graft has an initial success rate of approximately 90% and is a safe procedure (procedural death rate < 1%, myocardial infarction rate < 4%). The overall average restenosis rate is 42%. Surgical standby is limited and technically difficult. Angioplasty of chronic total occlusions in old grafts is associated with poor initial and long-term results. The long-term clinical results are unfavorable because of the continuing progression of disease in nontreated vein graft segments and native coronary arteries, in addition to the high restenosis rate. New techniques, although promising, have shown neither better initial results nor reduction of restenosis. Stent placement may be useful in longer graft lesions containing friable material. CONCLUSIONS: Patients may be classified into three groups according to expected early and late outcome on the basis of 1) unfavorable graft anatomy, 2) risk of cardiogenic shock in event of acute graft closure, and 3) age of grafts. The three groups are 1) those with an initial high success, low procedural risk and low restenosis rate; 2) those with an initial high success but high procedural risk and moderate to high restenosis rate; and 3) those with a low success, high risk and high restenosis rate. Balloon angioplasty to treat lesions in venous bypass grafts should be considered a palliative procedure, not a long-term solution, for ongoing progression of coronary artery and vein graft disease. The induced high restenosis rate remains a significant problem. PMID- 8496518 TI - Excimer laser-assisted coronary angioplasty for lesions containing thrombus. AB - OBJECTIVES: The purpose of this study was to analyze the success rates for excimer laser-assisted coronary angioplasty performed in patients undergoing angioplasty for lesions containing thrombus. BACKGROUND: The presence of intracoronary thrombus increases the risk of a poor clinical outcome after balloon angioplasty. The effect of intracoronary thrombus on the safety and efficacy of excimer laser-assisted coronary angioplasty is unknown. METHODS: Percutaneous excimer laser-assisted coronary angioplasty was attempted in 142 patients, of whom 12 had angiographic evidence of intracoronary thrombus in 14 lesions, defined as a filling defect surrounded by contrast medium or an area of contrast staining. RESULTS: Clinical success (< 50% residual stenosis without myocardial infarction, death or bypass surgery at any time during hospitalization) was achieved in 7 (58%) of the 12 patients with intracoronary thrombus, compared with 123 (95%) of the 130 patients without thrombus (p = 0.00001). Angiographic and clinical complications were more common in patients with thrombus: embolization (25% vs. 1%, p < 0.001), myocardial infarction (33% vs. 2%, p < 0.001), abrupt closure (17% vs. 4%, p = 0.049). Angiographic restenosis at 6 months was seen at 7 (70%) of 10 treated sites with intracoronary thrombus and at 59 (51%) of 116 sites without thrombus (p = 0.245). Presence of intracoronary thrombus was identified as the most important predictor of clinical success (p = 0.013) by multivariable logistic regression analysis, which controlled for other co-variables, such as lesion complexity or lesion location in a saphenous vein graft. CONCLUSIONS: This analysis shows that the success of excimer laser-assisted coronary angioplasty is compromised when thrombus is detected angiographically. Further investigation of other strategies is needed to improve the outcome of angioplasty for this challenging problem. PMID- 8496519 TI - Serial angiographic follow-up after Palmaz-Schatz stent implantation: comparison with conventional balloon angioplasty. AB - OBJECTIVES: Serial angiographic follow-up study was designed to evaluate the temporal mode of lumen diameter changes after Palmaz-Schatz stent implantation, and the results were compared with those from a cohort of patients undergoing balloon angioplasty. BACKGROUND: Restenosis remains a major limitation of balloon angioplasty. The Palmaz-Schatz balloon expandable coronary stent is now under clinical investigation to evaluate its efficacy in preventing restenosis. METHODS: Serial angiographic follow-up study was performed the day after stent implantation and at 1, 3 and 6 months after the procedure. The stent group consisted of 96 patients who had 97 lesions with a single stent. A cohort of 179 patients with 192 lesions were selected as the balloon group by the criteria of final balloon size > or = 3 mm and lesion length < 20 mm. RESULTS: A significantly larger lumen diameter was obtained immediately after stent implantation (2.9 +/- 0.4 mm [mean +/- SD] in the stent group vs. 2.1 +/- 0.5 mm in the balloon group, p < 0.001). At 3 to 6 months of follow-up, a significantly larger lumen diameter was maintained in the stent group (2.2 +/- 0.6 vs. 1.5 +/- 0.7 mm, p < 0.001). The late restenosis rate according to a binary definition was significantly lower in the stent group (13% vs. 39%, p < 0.001). Stenosis exacerbation, frequently observed within 24 h after balloon angioplasty, was not found after stenting. Between the next day and 1 month, regression was dominant in the balloon group, whereas progression of stenosis was observed in the stent group. The greatest tendency to restenosis was observed in both groups between 1 and 3 months after the procedure. Between 3 and 6 months, significantly greater diameter loss was found in the stent group. CONCLUSIONS: The Palmaz-Schatz stent was effective in reducing the restenosis rate in this highly selected cohort of patients. Reduction in restenosis rate was dependent on a larger lumen obtained immediately. Late loss of diameter was significantly greater after stenting. The restenosis rate after stenting should be evaluated by follow-up angiography at 6 months rather than at 3 months, which is adequate after conventional balloon angioplasty. PMID- 8496520 TI - Atherectomy of the subclavian artery for patients with symptomatic coronary subclavian steal syndrome. AB - OBJECTIVES: This study addresses the efficacy of directional atherectomy in the subclavian artery for the relief of angina in patients with the coronary subclavian steal syndrome. In addition, we review the histologic findings from the atherectomy specimens. BACKGROUND: The coronary-subclavian steal syndrome may occur after internal mammary-coronary artery bypass grafting. It is due to a stenosis in the subclavian artery proximal to the origin of the internal mammary artery and causes frank ischemia to the area supplied by the graft. Currently, surgery is the corrective procedure of choice. METHODS: In three patients with severe subclavian artery stenoses and unstable angina, directional atherectomy was performed using a peripheral atherectomy catheter through a percutaneous femoral approach. The patients ranged from 43 to 71 years of age and had undergone internal mammary-coronary artery bypass grafting 3 to 10 years previously. Each patient had severe peripheral vascular and cerebrovascular disease. RESULTS: All three patients had immediate symptomatic relief after the atherectomy, and postprocedure exercise testing demonstrated improved cardiac function. Two patients remain asymptomatic at 7 and 8 months, respectively; the third patient developed unstable angina 9 months later because of severe restenosis that was again successfully treated with atherectomy. Histologic examination of the specimens revealed atherosclerotic plaque, occasionally with adventitia. The specimen from the repeat atherectomy showed severe intimal hyperplasia. CONCLUSIONS: Directional atherectomy appears to be a safe and effective treatment for coronary-subclavian steal syndrome. This procedure may be the treatment of choice for patients in whom a vascular bypass operation is not feasible. PMID- 8496521 TI - Mitral valve area calculations immediately after percutaneous balloon mitral valvuloplasty: effect of the atrial septal defect. AB - OBJECTIVES: The aim of this study was to assess the effect of the atrial septal defect on mitral valve area calculations after balloon mitral valvuloplasty. BACKGROUND: There is poor correlation between the hemodynamic-derived and Doppler mitral valve area immediately after mitral valvuloplasty. The reasons for this are unclear. METHODS: Twenty-five patients with severe mitral stenosis were studied. After balloon mitral valvuloplasty, serial mitral valve area calculations were performed with 1) the mitral dilating catheter across the atrial septum, 2) the 7F catheter across the atrial septum, and 3) with the atrial puncture site occluded with the balloon catheter. RESULTS: The mitral valve area determined by the Gorlin formula with balloon occlusion of the atrial septum was smaller than the mitral valve area determined without balloon occlusion (mean +/- SD 1.8 +/- 0.43 vs. 2.24 +/- 0.67 cm2, p < 0.005 for the mitral dilating catheter across the atrial septum and 1.8 +/- 0.43 vs. 2.19 +/- 0.52, p < 0.05 for the 7F catheter across the atrial septum). The mean of the differences between the mitral valve area derived by the Gorlin formula and by the Doppler pressure half-time method was smaller with the atrial septum occluded than when the dilating catheter or the 7F catheter was across the atrial septum (0.12 +/- 0.26 vs. 0.56 +/- 0.48 cm2 [p < 0.005] and 0.12 +/- 0.26 vs. 0.48 +/- 0.55 cm2 [p < 0.05]). Left to right shunting was detected less frequently by oximetry (60%), than by shunt ratios calculated by using the cardiac output measurements with and without balloon occlusion of the atrial septum (84%). CONCLUSIONS: The presence of left to right shunts after mitral valvuloplasty may account for some of the discrepancies between mitral valve area found at cardiac catheterization and that by the Doppler pressure half-time method; thus, the latter method may be reliably used to follow up patients in the long term. PMID- 8496522 TI - Spectral analysis of flow velocity in the contralateral artery during coronary angioplasty: a new method for assessing collateral flow. AB - OBJECTIVES: The present study was designed to evaluate a new method for assessing coronary collateral flow and resistance in conscious humans. BACKGROUND: Earlier pathomorphologic and invasive studies have indicated that collateral vessels are important for salvage of myocardium at risk in acute myocardial infarction. Only a few clinical studies have attempted to express the development of the collateral vascular bed in terms of flow or resistance. METHODS: Angiography and flow velocity measurements of the contralateral coronary artery were performed in 38 patients undergoing coronary angioplasty for one-vessel disease. Coronary flow velocity was assessed by zero-crossing frequency analysis in 37 patients and, additionally, by fast Fourier transform spectral analysis in 23. Collateral flow was determined by the decrease of flow velocity after balloon deflation. Mean aortic pressure and coronary wedge pressure were assessed for calculation of collateral vascular resistance. RESULTS: Angiography of the contralateral artery during balloon inflation revealed the presence of collateral vessels in 26 patients (recruitable collateral vessels in 19). Fast Fourier transform spectral analysis demonstrated a significant transient increase of flow velocity during brief coronary occlusion in 15 patients with collateral vessels compared with 8 patients without collateral vessels (4.8 +/- 1.3% vs. 23.4 +/- 17.2%, p < 0.001). A transient increase in flow velocity (> 10%) was less evident by zero-crossing frequency analysis than by fast Fourier transform spectral analysis (sensitivity 8% vs. 87%). The relative resistance of the collateral vascular bed was significantly reduced when collateral vessels were present during coronary occlusion (4.4 +/- 3.8 vs. 16.9 +/- 4.6, p < 0.001). Furthermore, electrocardiographic signs of ischemia were less present in those 15 patients with collateral vessels (p < 0.05). CONCLUSIONS: The beneficial effect of collateral vessels during brief coronary occlusion is exerted by a significant increase of flow in the contralateral artery in combination with a reduced resistance in the collateral vascular bed. The method presented is capable of expressing the development of the collateral vascular bed in terms of flow and resistance. PMID- 8496523 TI - Dobutamine thallium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing. AB - OBJECTIVES: The aim of this study was to assess the feasibility, safety and diagnostic accuracy of a high dose dobutamine infusion in conjunction with thallium-201 single-photon emission computed tomography in 144 patients (72 men and 72 women with a mean age of 65 +/- 10 years) unable to perform exercise or pharmacologic vasodilator stress testing. BACKGROUND: Dobutamine increases myocardial oxygen consumption by increasing heart rate, contractility and arterial blood pressure. In addition, it causes myocardial blood flow heterogeneity and thus may be a useful stress for noninvasive detection of coronary artery disease. METHODS: Dobutamine was administered intravenously at incremental doses of 5, 10, 20, 30 and up to 40 micrograms/kg per min at 3-min intervals. After 1 min of the maximal dose, 3 mCi of thallium-201 was injected and the infusion was continued for an additional 2 min. Thallium-201 tomography was performed 5 to 10 min after termination of the infusion and 4 h later. The images were visually assessed for the presence and vascular location of perfusion defects and the extent of thallium redistribution. Coronary angiography was performed in 84 patients, with a > 50% stenosis considered significant. RESULTS: Dobutamine significantly (p = 0.0001) increased the heart rate (from 75 +/- 14 beats/min to 120 +/- 23 beats/min), systolic blood pressure (from 136 +/- 23 mm Hg to 148 +/- 35 mm Hg) and the rate-pressure product (from 10,144 +/- 2,517 to 17,858 +/- 4,349) from baseline to peak infusion rate, respectively. Most patients (75%) experienced side effects during the infusion, but 74% tolerated a dobutamine dose of 40 micrograms/kg per min and 97% a dose of 30 micrograms/kg per min. The more common side effects were typical (26%) and atypical (5%) chest pain, palpitation (29%), flushing (14%), headache (14%) and dyspnea (14%). The overall sensitivity of dobutamine tomography was 86% in the patients who underwent coronary angiography and 84% in those with single-vessel, 82% in those with double-vessel and 100% in those with triple-vessel disease. Seventy-eight percent of vessels with severe (> or = 70%) stenoses were identified with dobutamine tomography. The specificity of dobutamine tomography was 90% for patients and 86% for individual vessels. CONCLUSIONS: A high dose dobutamine infusion in conjunction with thallium tomography appears to be a well tolerated and accurate method for diagnosing coronary artery disease in patients unable to perform exercise or vasodilator pharmacologic stress testing. PMID- 8496524 TI - Simultaneous dobutamine stress echocardiography and technetium-99m isonitrile single-photon emission computed tomography in patients with suspected coronary artery disease. AB - OBJECTIVES: The purpose of this study was to determine the relative value of dobutamine stress echocardiography and technetium-99m isonitrile single-photon emission computed tomography (mibi SPECT) in the detection of myocardial ischemia. BACKGROUND: Stress-induced new wall motion abnormalities and transient perfusion defects are both used for the diagnosis of myocardial ischemia. METHODS: One hundred five consecutive patients with either proved or suspected coronary artery disease, who were referred for perfusion scintigraphy, were studied by a combination of the two techniques. Both echocardiographic and mibi SPECT images were visually analyzed. Three patients were excluded from the final analysis because of unsatisfactory examinations: two with noninterpretable stress echocardiograms and one with noninterpretable mibi SPECT images. The response to stress was concordantly classified by both techniques in 68% of patients (kappa = 0.51). RESULTS: Dobutamine stress echocardiography revealed the presence of ischemia in 38 and mibi SPECT in 45 patients (overall agreement = 74%, kappa = 0.46). The agreement was higher in patients without previous myocardial infarction (84%, kappa = 0.62). When regional analysis was performed, concordance of stress echocardiography and mibi SPECT occurred in 84% of the 306 regions (kappa = 0.45). Regional agreement was also slightly higher in patients without previous infarction (88%, kappa = 0.50). In 21 patients without previous myocardial infarction who underwent coronary angiography, the overall sensitivity of dobutamine stress echocardiography and mibi SPECT for the diagnosis of coronary artery disease (diameter stenosis > 50%) was 75% and 83%, respectively, with a specificity of 89% (eight of nine patients) for both tests. CONCLUSIONS: Dobutamine stress echocardiography represents a reasonable alternative to dobutamine mibi SPECT for the functional assessment of patients with suspected myocardial ischemia and without previous myocardial infarction. PMID- 8496525 TI - Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon. AB - OBJECTIVES: The aim of this study was to test the hypothesis that the warm-up phenomenon is attributable to a reduction of increased myocardial oxygen consumption rather than to increased coronary blood flow during exercise. BACKGROUND: The underlying mechanism of the warm-up phenomenon is not elucidated. METHODS: Thirteen patients with effort angina were subjected to two consecutive supine ergometer exercise tests performed 15 min apart. All patients had severe proximal stenosis (> 90%) in the left anterior descending coronary artery. Great cardiac vein flow was measured before and during exercise. Both regional myocardial oxygen consumption and adenosine release were determined. RESULTS: Exercise was continued for significantly longer before angina onset in the second than in the first exercise test (507 +/- 44 vs. 410 +/- 42 s, p < 0.01). The extent of ST segment depression in lead V5 of the electrocardiogram (ECG) was larger at the time of angina onset in the first (1.7 +/- 0.2 mm) than in the second (1.1 +/- 0.2 mm, p < 0.01) exercise test. Neither systemic hemodynamic variables nor great cardiac vein flow differed between the first and second exercise tests. In contrast, regional myocardial oxygen consumption assessed at 3 min of exercise was significantly (p < 0.01) less in the second than in the first test (8.0 +/- 0.8 vs. 8.7 +/- 0.9 ml/min). Adenosine release during the second test was higher (p < 0.05) than in the first test (2.5 +/- 0.5 vs. 3.9 +/- 0.5 nmol/min at 3 min of the first and second tests, p < 0.01). CONCLUSIONS: These results indicate that the warm-up phenomenon is not attributable to increased coronary flow but to attenuation of increased regional myocardial oxygen consumption, which may be mediated by adenosine A1 receptor activation. PMID- 8496526 TI - Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. The Angina and Silent Ischemia Study Group (ASIS). AB - OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment. PMID- 8496527 TI - A simple technique for selective radiofrequency ablation of the slow pathway in atrioventricular node reentrant tachycardia. AB - OBJECTIVES: A simple technique was designed for radiofrequency ablation therapy of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: This technique was based on the hypothesis that slow pathway conduction reflects conduction through the compact node and its posterior atrial input. METHODS: A total of 100 consecutive patients were studied; there were 37 men and 63 women, with a mean age of 48 +/- 15 years. All 100 patients had induction of sustained tachycardia with (51 patients) or without (49 patients) administration of isoproterenol or atropine, or both. The ablation catheter was initially manipulated to record the largest His bundle deflection from the apex of Koch's triangle. It was then curved downward and clockwise to the area of the compact node when His deflection was no longer visible and the ratio of atrial to ventricular electrogram was < 1. The radiofrequency current was delivered from the 4-mm tip electrode a mean of 5 +/- 7 times at a power of 25 +/- 4 W for a duration of 21 +/- 4 s. The total fluoroscopic time was 19 +/- 11 min. RESULTS: Selective ablation (56 patients) or modification (26 patients) of the slow pathway without affecting anterograde and retrograde fast pathway conduction was achieved in 82 patients. Ablation or modification of both the retrograde fast pathway and the slow pathway but with preservation of anterograde fast pathway conduction was noted in 12 patients. Ablation or modification of the retrograde fast pathway alone or both anterograde and retrograde fast pathway conduction was noted in three patients. Complete AV node block occurred in three patients. Seventy-three patients had no induction of echo beats or tachycardia and 24 patients had induction of a single echo beat after ablation. Follow-up study was performed in 62 patients 76 +/- 18 days after ablation. Thirty-nine patients had no induction of echo beats or tachycardia, 22 had induction of echo beats alone and 1 patient had induction of sustained tachycardia. CONCLUSION: Selective ablation of the slow AV node pathway can be achieved by a simple procedure with a high success rate and few complications. PMID- 8496528 TI - What price success? PMID- 8496529 TI - Electrophysiologic variables characterizing the induction of ventricular tachycardia versus ventricular fibrillation after myocardial infarction: relation between ventricular late potentials and coupling intervals for the induction of sustained ventricular tachyarrhythmias. AB - OBJECTIVES: The aim of this study was to analyze the relations between the presence of ventricular conduction delay and the necessary coupling intervals for the induction of sustained ventricular tachyarrhythmias. METHODS: The electrophysiologic and signal-averaged electrocardiographic (ECG) data from 83 patients with previous myocardial infarction and inducible sustained monomorphic ventricular tachycardia (n = 71) and ventricular fibrillation (n = 12) were analyzed. RESULTS: The sum of the coupling intervals needed for inducing ventricular tachycardia and ventricular fibrillation was 485 +/- 59 ms and 387 +/ 36 ms, respectively (p < 0.001). The mean difference between the effective refractory period and the second coupling interval for the induction of ventricular tachycardia and ventricular fibrillation was -3 +/- 40 ms and 24 +/- 29 ms, respectively (p < 0.02). QRS duration and duration of terminal low amplitude signals of the QRS complex (p < 0.004) were longer in patients with inducible ventricular tachycardia than in patients with inducible ventricular fibrillation. The root mean square of the voltage during the last 40 ms of QRS complex was lower in patients with inducible ventricular tachycardia than in patients with inducible ventricular fibrillation (p < 0.007). Patients with inducible ventricular tachycardia presented with a greater prevalence of ventricular late potentials than that of patients with inducible ventricular fibrillation (p < 0.007). For arrhythmia induction, significantly shorter coupling intervals were necessary in patients without than in patients with ventricular late potentials. A positive correlation was found between the cycle length of the induced ventricular tachycardia and the filtered QRS duration as well as with the sum of the coupling intervals. CONCLUSIONS: Induction of ventricular fibrillation requires shorter coupling intervals than does induction of ventricular tachycardia. The presence of ventricular conduction delay seems to be a marker of facilitated induction of sustained monomorphic ventricular tachycardia rather than of ventricular fibrillation. The coupling intervals required to induce ventricular tachycardia or fibrillation are longer in patients with than in those without an abnormal signal-averaged ECG. PMID- 8496530 TI - Predictors of defibrillation efficacy in patients undergoing epicardial defibrillator implantation. The Multicenter Pacemaker-Cardioverter-Defibrillator (PCD) Investigators Group. AB - OBJECTIVES: The objective of this study was to identify predictors of defibrillation threshold in patients undergoing epicardial defibrillator implantation. BACKGROUND: Factors that predict epicardial defibrillation efficacy are poorly defined. METHODS: The data from 375 consecutive adult patients were reviewed. After exclusion of 137 patients in whom defibrillation threshold was not obtained, 238 patients (32 women and 206 men) with a mean age of 58.9 +/- 13.3 years formed the study group. Coronary heart disease was present in 175 patients and the mean left ventricular ejection fraction was 35.8 +/- 15.4%. At device implantation, three epicardial patch sizes were available and shocks could be delivered over one current pathway (two patches) or over two current pathways (three patches with simultaneous or sequential shocks). Defibrillation threshold was defined as the lowest programmed energy that successfully defibrillated the heart, provided there had been an unsuccessful shock at a lower energy level or successful defibrillation at < or = 5 J. RESULTS: The mean defibrillation threshold was 8.6 +/- 5.3 J. With univariate analysis, female gender, sequential shocks with three patches, higher left ventricular ejection fraction and lower New York Heart Association functional class predicted a lower defibrillation threshold. In the multivariate analysis, female gender (coefficient -3.9; 95% confidence interval [CI] -1.9 to -5.0 J), ejection fraction (coefficient -0.6; CI -0.1 to -1.0 J/decile) and sequential shocks (coefficient -2.5; CI -1.0 to -4.0 J) were independently associated with a lower defibrillation threshold. Total epicardial patch conductive surface area normalized to body surface area reached borderline significance (coefficient 0.004; CI 0 to 0.01; p = 0.10). Antiarrhythmic drug use, including amiodarone, did not predict defibrillation threshold. CONCLUSIONS: Female gender, high left ventricular ejection fraction and the use of sequential pulse shocks were important determinants of improved defibrillation efficacy. PMID- 8496531 TI - Do patients with an implantable defibrillator live longer? AB - OBJECTIVES: This study was done to provide information on the potential benefit of implantable cardioverter-defibrillator therapy regarding sudden and arrhythmia related deaths and to examine whether such therapy improves survival. BACKGROUND: Implantation of automatic cardioverter-defibrillators is reported to abort sudden cardiac death due to malignant tachyarrhythmias. METHODS: Between 1989 and 1992, 107 patients were screened for implantation of a third-generation implantable cardioverter-defibrillator combined with endocardial leads. Mean age was 57 +/- 13 years and mean ejection fraction was 40 +/- 15%. Sudden death, total arrhythmia-related death and total cardiac death were compared with the occurrence of fast ventricular tachyarrhythmias (> 240 beats/min), assuming that most of these arrhythmias would have been fatal without treatment by the implantable cardioverter-defibrillator. RESULTS: The surgical mortality rate was 2.7% in all 107 patients and 1% in the 99 patients who qualified for endocardial leads. During a follow-up period of 12 +/- 8 months, actuarial survival rate free of events at 6 months as well as at 12 and 18 months was 100% for sudden death, 97% for total arrhythmia-related death and 95% for total cardiac death. In contrast, after 6, 12 and 18 months, the rate of survival free of fast ventricular tachycardia was only 83%, 74% and 69%, respectively, and the rate of survival free of any ventricular tachyarrhythmia was only 59%, 49% and 40%, respectively. CONCLUSIONS: The outcome of patients treated with an implantable cardioverter-defibrillator and endocardial defibrillation leads is excellent. For many patients, this treatment is probably lifesaving. PMID- 8496532 TI - Global T wave inversion: long-term follow-up. AB - OBJECTIVES: This study evaluated 11-year follow-up data from patients with global T wave inversion. BACKGROUND: In an 8-year prospective investigation, global T wave inversion was characterized by a long QT interval, unexplained marked female preponderance and, despite dramatic electrocardiographic (ECG) changes, an in hospital prognosis not statistically different from that of the entire hospital population in which the condition it occurred. METHODS: To assess long-term prognosis, these and an additional 18 patients (total 118 patients; 92 women and 26 men) with global T wave inversion were followed up prospectively for up to 11 years (mean 33.9 +/- 37.3 months). The additional patients did not significantly affect the in-hospital death rate (7.6%; previously reported death rate 8%) and the total series continued not to differ from the entire in-hospital population in which it occurred (7.02%; p = NS). RESULTS: Long-term survival was shortened by digoxin, faster heart rates, atrial fibrillation and, especially, a malignant condition. Eighteen (78.3%) of 23 patients with a malignant condition died during the follow-up period (p < or = 0.0005), with a mean survival time of only 12 months. Kaplan-Meier curves also revealed the poor prognosis for those patients taking digoxin; 21 (63.9%) of 36 patients died (p = 0.008). Eleven of the 12 patients with atrial fibrillation were taking digoxin; 58.3% of these died, demonstrating a worse prognosis than that of patients with sinus rhythm, 35% of whom died (p = 0.005). CONCLUSIONS: Global T wave inversion continues to have an unexplained (78% vs. 22%) female preponderance. Although the long-term prognosis depends on underlying or associated diseases, the striking diffuse ECG changes do not in themselves imply a poor prognosis. PMID- 8496533 TI - Prognosis after valve replacement in patients with severe aortic stenosis and a low transvalvular pressure gradient. AB - OBJECTIVES: This study was conducted to determine the risks and benefits of valve replacement in patients with severe aortic stenosis and a low transvalvular pressure gradient. BACKGROUND: There is uncertainty regarding the appropriate management of adults with severe aortic stenosis and a transvalvular pressure gradient < or = 30 mm Hg. With only six such patients reported, one study suggested that these subjects have a prohibitive operative risk and little symptomatic improvement if they survive surgical treatment, whereas another showed that they can survive an operation and improve symptomatically. METHODS: In an attempt to clarify the risks and benefits of valve replacement in these patients, we reviewed the records of 18 patients (15 men and 3 women, aged 49 to 81 years) with severe aortic stenosis (valve area < or = 0.4 cm2/m2 body surface area), a mean transvalvular pressure gradient < or = 30 mm Hg and limiting symptoms (New York Heart Association functional class III or IV) who underwent valve replacement. RESULTS: Six patients (33%) (95% confidence interval 13% to 59%) died perioperatively, whereas 10 patients (56%) (95% confidence interval 31% to 78%) improved symptomatically to functional class I (n = 8) or II (n = 2) (p = NS in comparison with the 6 who died). No clinical or hemodynamic variable was predictive of survival or improvement in functional class. CONCLUSIONS: Valve replacement in patients with severe aortic stenosis and a transvalvular pressure gradient < or = 30 mm Hg is accompanied by a considerable operative risk. Although there were no significant differences in this small series between the fraction of patients who died and those who exhibited improvement, we still recommend the procedure because many patients survive the operation and most of the survivors show an improved symptomatic status. PMID- 8496534 TI - Effect of thrombolytic therapy on the evolution of significant mitral regurgitation in patients with a first inferior myocardial infarction. AB - OBJECTIVES: This study was designed to test the hypothesis that reperfusion therapy with thrombolysis will prevent the development of significant mitral regurgitation in patients with inferior myocardial infarction. BACKGROUND: The value of thrombolytic therapy in patients with inferior or posterior wall myocardial infarction has been controversial. We hypothesized that successful reperfusion therapy with intravenous thrombolysis may reduce the incidence and severity of postinfarction mitral regurgitation in this patient group. METHODS: We prospectively studied 104 patients with a first inferior myocardial infarction. Thrombolytic therapy was administered to 55 patients (treatment group) 3.2 +/- 2.1 h after the onset of symptoms. The other 49 patients formed the control group. Doppler echocardiographic color flow imaging was performed in all patients within 24 h, at 7 to 10 days and at 28 to 30 days after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3). RESULTS: No significant differences in baseline clinical characteristics were observed between the treatment and control groups. The overall incidence rates of significant mitral regurgitation at 24 h, 7 to 10 days and at 28 to 30 days were 10 (10%) of 104 patients, 18 (17%) of 104 patients and 11 (11%) of 100 patients, respectively. Multivariate analysis reveals the following independent predictors of the occurrence of significant mitral regurgitation: female gender (at 7 to 10 days, odds ratio 5.3, 90% confidence interval [CI] 1.8 to 15.5; at 28 to 30 days, odds ratio 3.7, 90% CI 1.1 to 12.7), heart failure (at 7 to 10 days, odds ratio 7.7, 90% CI 2.2 to 26.9) and transient complete atrioventricular block (at 24 h of myocardial infarction, odds ratio 5.8, 90% CI 1.2 to 27). Compared with the control group, the treatment group exhibited marked reduction in the incidence of significant mitral regurgitation at 24 h (16% vs. 4%; odds ratio 0.1, 90% CI 0.0 to 0.7); at 7 to 10 days (24% vs. 11%; odds ratio 0.3, 90% CI 0.1 to 0.9) and at 28 to 30 days (15% vs. 7%; odds ratio 0.4, 90% CI 0.1 to 1.6). Severe (grade 3) mitral regurgitation developed in five patients in the control group but in no patient in the treatment group. CONCLUSIONS: Thrombolytic therapy in the patients with a first inferior myocardial infarction was associated with a reduced incidence of significant mitral regurgitation. These results support the use of such therapy in patients with inferior myocardial infarction. PMID- 8496535 TI - Active myocardial damage without attending inflammatory response in dilated cardiomyopathy. AB - OBJECTIVES: This study aimed to compare indium-111 (111In)-monoclonal antimyosin antibody uptake in patients with dilated cardiomyopathy before heart transplantation with the histologic findings in the explanted hearts. BACKGROUND: A high prevalence of 111In-monoclonal antimyosin antibody uptake has been described in patients with dilated cardiomyopathy, suggesting the presence of active, ongoing myocyte damage; however, no correlation between monoclonal antimyosin antibodies and histologic findings is available in these patients. METHODS: A consecutive series of 21 patients with dilated cardiomyopathy awaiting heart transplantation were studied with monoclonal antimyosin antibodies before the operation, and the results were compared with the histologic analysis of the explanted hearts. The interval between monoclonal antimyosin antibody studies and transplantation was 1 to 90 days (mean 58 +/- 31). RESULTS: Using a semiquantitative method (heart/lung ratio), monoclonal antimyosin antibody uptake was present in 15 (71%) of 21 patients, but active myocarditis in the explanted hearts was detected in only 7. In 11 patients, intense monoclonal antimyosin antibody uptake coexisting with absent myocyte damage or cellular infiltration of explanted hearts was noted. One patient who showed preoperative monoclonal antimyosin antibody uptake underwent transplantation 11 h later, and ex vivo diffuse myocardial antimyosin uptake was detected, but active myocarditis was seen only at cardiectomy in only a small area of the heart; the rest of the myocardium showed no signs of myocyte damage. CONCLUSIONS: In dilated cardiomyopathy, monoclonal antimyosin antibody uptake cannot be equated with the presence of an inflammatory response detected in the myocardium of the explanted heart. PMID- 8496536 TI - A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy. AB - OBJECTIVES: The aim of this study was to determine whether therapy with a beta adrenergic or calcium channel blocking agent can improve the functional capacity and quality of life of patients with mild or moderately symptomatic hypertrophic cardiomyopathy. BACKGROUND: Both beta-blockers and calcium channel blockers may alleviate symptoms in hypertrophic cardiomyopathy, but previous studies have been performed in hospitalized patients or have been open studies without control subjects. METHODS: A randomized, double-blind crossover trial of nadolol, verapamil and placebo, administered for periods of 4 weeks each, was performed in 18 patients with mild or moderately symptomatic hypertrophic cardiomyopathy (10 men, 8 women; mean age +/- SD 39 +/- 17 years). A detailed symptom assessment, bicycle exercise testing, echocardiography and Holter monitoring were performed in each period. RESULTS: Two patients withdrew from the study owing to symptomatic sinus bradycardia during nadolol therapy. Neither drug improved maximal oxygen consumption (placebo 26 +/- 8, verapamil 23 +/- 6, nadolol 21 +/- 7 ml/kg per min; p = 0.1). Peak exercise work load was reduced by > or = 10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (p = 0.005, nadolol vs. verapamil). Despite the effects on exercise capacity, 13 patients (81%) preferred drug treatment (8 verapamil, 5 nadolol) over placebo (p = 0.001). Verapamil improved reported performance at work compared with nadolol (p = 0.01) and tended to improve other measures of health related behavior and symptoms compared with nadolol and placebo. CONCLUSIONS: In patients with mild or moderately symptomatic hypertrophic cardiomyopathy, exercise capacity was not improved by nadolol or verapamil, and individuals were more often impaired by nadolol than with verapamil. Nevertheless, many patients derived symptomatic benefit from drug therapy, especially with verapamil. PMID- 8496537 TI - Improved detection of echocardiographic left ventricular hypertrophy using a new electrocardiographic algorithm. AB - OBJECTIVES: The purpose of this study was to use the Framingham data base to devise and test an improvement in an electrocardiographic (ECG) voltage criterion for detecting left ventricular hypertrophy that is gender specific and adjusts for age and obesity. BACKGROUND: Electrocardiographic detection of left ventricular hypertrophy has been receiving increasing attention. The "Cornell" ECG voltage, defined as the sum of voltages for the R wave of lead aVL and S wave of lead V3, has been shown to correlate strongly with echocardiographically estimated left ventricular mass. Because the magnitude of this voltage varies with both age and obesity, we have proposed a simple formula for its adjustment for these two variables. METHODS: Using linear regression, the adjustment formula was estimated from data on 1,468 men and 1,883 women from the Framingham Heart Study cohort who were free of myocardial infarction and who had both an ECG and an echocardiogram recorded during the same clinic examination. A modified receiver operating characteristic curve method was used to compare sensitivities at the same specificity levels. The adjustment formula was estimated from one randomly chosen half of the study cohort and applied to the other half for evaluation. RESULTS: Significant improvement in sensitivity for the detection of left ventricular hypertrophy was realized at all levels of specificity. At a specificity level of 98%, the adjustment increased the sensitivity of the Cornell voltage from 10% to 17% in men and from 12% to 22% in women. For severe hypertrophy, defined as a left ventricular mass > 3 SD above the gender-specific mean, the sensitivity increased from 23% to 38% for men and from 22% to 55% for women at a specificity level of 95%. CONCLUSIONS: This approach can substantially enhance the utility of the ECG for the detection of left ventricular hypertrophy. If these results are validated in other population groups, this approach may prove valuable in the screening of hypertensive populations and for the monitoring of patients undergoing treatment for hypertension. PMID- 8496538 TI - Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. AB - OBJECTIVES: This study was conducted to investigate whether pulmonary venous flow variables measured by transthoracic Doppler ultrasound can help identify patients with elevated left ventricular end-diastolic or filling pressures, or both. BACKGROUND: A widened left atrial pressure A wave occurs when left ventricular end-diastolic pressure is increased. Increased duration of pulmonary venous flow reversal at atrial systole might therefore be a marker for elevated end-diastolic pressure. Decreased systolic pulmonary venous flow is shown to be related to increased left ventricular filling pressure in studies using transesophageal Doppler echocardiography. METHODS: Left ventricular pressures at late diastole were measured by fluid-filled catheters in 50 consecutive patients undergoing diagnostic cardiac catheterization. Pulmonary venous and mitral flow velocities were recorded by transthoracic pulsed Doppler ultrasound. RESULTS: Adequate recordings were obtained in 45 patients. Pulmonary venous flow reversal exceeding the duration of the mitral A wave predicted left ventricular end-diastolic pressure > 15 mm Hg with a sensitivity of 0.85 and a specificity of 0.79. This difference in flow duration correlated well with the increase in ventricular pressure (r = 0.70, p < 0.001) at atrial systole and the end-diastolic pressure (r = 0.68, p < 0.001). The systolic fraction of pulmonary venous flow was markedly decreased (< 0.4) in all patients with a pre-A pressure (left ventricular pressure before atrial systole) > 18 mm Hg. CONCLUSIONS: Pulmonary venous flow reversal exceeding the duration of the mitral A wave indicates an exaggerated increase in left ventricular late diastolic pressure. Pulmonary venous systolic fraction < 0.4 suggests markedly increased ventricular filling pressure. PMID- 8496539 TI - Doppler assessment of left ventricular diastolic function: the refinements continue. PMID- 8496540 TI - Net costs from three perspectives of using low versus high osmolality contrast medium in diagnostic angiocardiography. AB - OBJECTIVES: We conducted an economic analysis to assess the extent to which a reduction in adverse drug reactions induced by low osmolality compared with high osmolality contrast media during diagnostic angiocardiography would result in savings to hospitals, society and third-party payers that would offset the substantially higher price of low osmolality contrast medium. BACKGROUND: Substitution of low osmolality for high osmolality contrast media in the approximately 1 million diagnostic angiocardiographic procedures performed each year in the United States could substantially increase health care costs. Cost effectiveness estimates should include savings that might occur through reduced costs of managing adverse drug reactions. METHODS: In a randomized clinical trial of 505 persons under-going diagnostic angiography with either high osmolality or low osmolality contrast medium, we measured and compared 1) material costs of contrast media, and 2) costs from three perspectives of incremental resources used to manage contrast-related adverse drug reactions. We also performed sensitivity analyses to examine the effect of different assumptions with regard to relative risk, absolute risk and costs of adverse drug reactions on estimates of net cost of use of high osmolality and low osmolality contrast media. RESULTS: One-hundred thirty-seven (54.2%) of 253 patients receiving high osmolality contrast medium and 44 (17.5%) of 252 patients receiving low osmolality contrast medium experienced adverse drug reactions. The average cost (from society's perspective) of resources used to manage adverse drug reactions per patient undergoing angiography was significantly (p = 0.0001) greater for high osmolality (mean $249) versus low osmolality (mean $92) contrast medium. Differential costs (from the hospital's perspective) were $67 greater for high osmolality contrast medium. Charges and professional fees (from the payer's perspective) were $182 greater for high osmolality (mean $312) than for low osmolality (mean $130) contrast medium (p = 0.42, NS). The higher differential and average costs of managing adverse drug reactions with high osmolality contrast medium offset 33% and 75%, respectively, of the $207 difference in mean material costs, but these estimates are sensitive to infrequent high cost cases. CONCLUSIONS: Although low osmolality contrast medium is not cost-saving in diagnostic angiocardiography, its higher price is partially offset by lower management costs of adverse drug reactions. The cost offset for the hospital is lower than that for society and may not be realized by third-party payers. These methods and results may be useful in establishing clinical and payment guidelines for use of alternative contrast media in diagnostic angiocardiography. PMID- 8496541 TI - Economic evaluation of low osmolality contrast media. PMID- 8496542 TI - Conal anatomy in 119 patients with d-loop transposition of the great arteries and ventricular septal defect: an echocardiographic and pathologic study. AB - OBJECTIVES: We sought to study the range of conal morphology in transposition of the great arteries with ventricular septal defect and their embryologic and surgical implications. BACKGROUND: Conal anatomy in transposition of the great arteries and ventricular septal defect is variable and might affect surgical repair. METHODS: Conal anatomy was explored using two-dimensional echocardiography in 119 patients with transposition of the great arteries and a large ventricular septal defect who presented between 1984 and 1991. The influence of conal anatomy on surgical technique was determined by review of the operative reports. Specimens of transposition of the great arteries with unusual conal anatomy were selected from the Cardiac Registry for comparison with the echocardiograms. RESULTS: One hundred five patients (88.2%) had subaortic conus only with no subpulmonary conus (Group 1). Subarterial conus was present bilaterally in eight patients (6.7%) (Group 2). Four patients (3.4%) had only subpulmonary conus with no (or minimal) subaortic conus (Group 3). Among these four patients, the aorta was posterior to the pulmonary artery in one patient, side by side relative to the pulmonary artery in two patients and slightly anterior in the fourth patient. Subarterial conus was absent bilaterally in two patients (1.7%) (Group 4); the aorta was slightly posterior in one and side by side with the pulmonary artery in the other. CONCLUSIONS: This variability of conal anatomy in transposition of the great arteries with ventricular septal defect implies four mechanisms by which transposition can occur. The conal anatomy appeared to affect surgical repair in Groups 1 and 2 insofar as it influenced ventricular outflow tract obstruction. In Groups 3 and 4, an arterial switch operation was performed in four of the six patients. The posterior location of the aorta obviated the need for the Lecompte maneuver in two of these four patients. In the remaining two cases in Groups 3 and 4, the condition was repaired by directing the left ventricular outflow across the ventricular septal defect to the aorta using a patch, with or without placement of a conduit from the right ventricle to the pulmonary artery. PMID- 8496543 TI - Ethnicity and socioeconomic status: impact on the diagnosis of congenital heart disease. AB - OBJECTIVES: The purpose of this study was to estimate the prevalence rates of specific cardiac defects for three ethnic groups and to determine the effects of ethnicity, family income and household education level on the timing of referral for pediatric cardiac care. BACKGROUND: Previous studies examining ethnic differences in rates of congenital heart disease were based on hospital referrals or were limited to diagnoses made in the 1st year of life. These limitations may lead to potential biases in the ascertainment of cases. The present study is population based and includes patients diagnosed after the 1st year of life. METHODS: Cases of congenital heart disease were enumerated among 379,561 liveborn infants to black, white and Mexican-American residents in Dallas County, Texas. Diagnosis was made on the basis of examination by a pediatric cardiologist, two dimensional echocardiographic studies, cardiac catheterization or observations at operation or at autopsy. Ethnicity, median family income and household educational level were determined from birth certificate information. RESULTS: White children had higher prevalence rates for aortic stenosis, endocardial cushion defect and ventricular septal defect. Mexican-American children had the lowest rate for hypoplastic left heart syndrome. The median age at referral to a pediatric cardiologist was 1.9 months for blacks, 2.1 months for whites and 2.2 months for Mexican-Americans. Stratifying the cases by median family income and household educational level failed to show any significant relation to age at referral. CONCLUSIONS: Prevalence rates of specific cardiac defects vary among black, white and Mexican-American children, probably reflecting different genetic and environmental backgrounds. The timing of referral for pediatric cardiac care, however, was not related to ethnicity, median family income or household educational level. PMID- 8496544 TI - Generalized arteriopathy in Williams syndrome: an intravascular ultrasound study. AB - OBJECTIVES: We used intraluminal ultrasound imaging to provide additional information about the vascular pathology in Williams syndrome. BACKGROUND: The cardiovascular pathology of Williams syndrome consists of medial hypertrophy in both systemic and pulmonary arteries, which results in lumen narrowing. METHODS: Systemic and pulmonary arteries were examined in vivo using intravascular ultrasound imaging (5F, 30-MHz catheter) in three children with Williams syndrome. RESULTS: All arteries exhibited severe wall thickening with secondary lumen narrowing. Balloon dilation of a branch pulmonary artery in two children resulted in a significant localized increase in lumen caliber associated with a tear in the vessel wall. CONCLUSIONS: Intravascular ultrasound imaging in patients with Williams syndrome may permit better understanding of the pathophysiology of the syndrome and a more rational approach to therapeutic interventions. PMID- 8496545 TI - Rapid ventricular pacing in dogs with right ventricular outflow tract obstruction: insights into a mechanism of sudden death in postoperative tetralogy of Fallot. AB - OBJECTIVES: We explored the hypothesis that residual outflow tract obstruction and ventricular hypertrophy associated with rapid ventricular rhythm contribute to sudden death, in part because they result in humoral or hemodynamic changes that predispose to ventricular fibrillation, such as increased catecholamine release or decreased coronary flow, or both. BACKGROUND: Ventricular arrhythmia after surgical repair of tetralogy of Fallot has been associated with sudden death, particularly in patients with residual right ventricular hypertension. However, the mechanisms by which sudden death occurs remain unclear. METHODS: Seven awake, unanesthetized mature beagles with chronically elevated right ventricular pressure (high pressure group: right ventricular/left ventricular systolic pressure ratio > 0.5) were compared with six beagles with low right ventricular pressure at rest and at the end of 5 min of ventricular pacing at 240 beats/min (low pressure group). RESULTS: In the high pressure group, cardiac output decreased during ventricular pacing (compared with sinus rhythm) from 304 +/- 21 to 218 +/- 21 ml/min per kg (p < 0.01) and plasma norepinephrine increased substantially from 673 +/- 64 to 1,047 +/- 92 pg/ml (p < 0.01). Comparable changes were not observed in the low pressure group. Plasma epinephrine levels were similar in both groups at rest and did not change with pacing. Postpacing norepinephrine levels from both groups correlated positively with both right ventricular systolic and diastolic pressure at rest and correlated negatively with the change in cardiac output from rest to pacing. Regional right ventricular myocardial blood flow increased with pacing in the low pressure group, whereas in the high pressure group it was increased at rest and did not increase further with pacing. CONCLUSION: During ventricular pacing, dogs with right ventricular outflow tract obstruction and high right ventricular pressure had a decrease in cardiac output and an increase in plasma norepinephrine, coupled with a loss of right ventricular myocardial blood flow reserve. Similar changes may occur in postoperative patients with similar hemodynamics and tachyarrhythmia and could contribute to the occurrence of ventricular fibrillation and sudden death. PMID- 8496546 TI - From the bedside to the basic science laboratory: arrhythmias in Fallot's tetralogy. PMID- 8496547 TI - Accurate systolic wall thickening by nuclear magnetic resonance imaging with tissue tagging: correlation with sonomicrometers in normal and ischemic myocardium. AB - OBJECTIVES: This study examined whether the correlation of systolic wall thickening (%WT) by nuclear magnetic resonance (NMR) imaging with wall thickening by sonomicrometry (SM) is improved by using a three-dimensional volume element model of the left ventricular wall. BACKGROUND: Left ventricular wall obliquity with respect to the imaging plane causes overestimation of wall thickness by planar imaging techniques. Wall thickness perpendicular to the endocardial surface can be accurately calculated by three-dimensional reconstruction of left ventricular wall segments. METHODS: Sonomicrometers were placed transmurally in 11 dogs (left anterior descending artery territory) with an imaging marker, visible on NMR imaging, sewn to the epicardial crystal. Two adjacent NMR short axis image planes were radially segmented by four perpendicular spin-saturated planes (tags), dividing the myocardium into eight volume elements, one of which contained the sonomicrometer crystal pair. Left ventricular thickness and thickening were calculated by four methods: 1) linear = distance between epicardium and endocardium at midpoint in the segment with the sonomicrometer; 2) planar = area of that segment divided by the mean of the endocardial and epicardial arc lengths; 3) biplanar = average of wall thicknesses calculated by the planar method from the segment with sonomicrometers and the corresponding segment located in the adjacent short-axis imaging plane; and 4) three dimensional = volume of the element with the sonomicrometers divided by the mean of the endocardial and epicardial surface areas. RESULTS: Regressions for all methods using pooled data from control periods and during ischemia: Linear %WT = 0.59 + 1.31 SM%WT (r = 0.71, SEE = 0.28, p < 0.0002) Planar %WT = 1.43 + 1.62 SM%WT (r = 0.87, SEE = 0.19, p < 0.0001) Biplanar %WT = 2.09 + 1.46 SM%WT (r = 0.90, SEE = 0.15, p < 0.0001) Three-dimensional %WT = 0.19 + 1.49 SM%WT (r = 0.95, SEE = 0.10, p < 0.0001) CONCLUSIONS: Nuclear magnetic resonance imaging with tissue tagging allows accurate noninvasive assessment of systolic wall thickening. The three-dimensional volume element approach, by accounting for obliquity between the image plane and the left ventricular wall, provides the strongest correlation between NMR imaging and percent systolic wall thickening by sonomicrometer crystals. PMID- 8496548 TI - In defense of physicians. PMID- 8496549 TI - President's page: toward an ACC cardiovascular policy institute. PMID- 8496550 TI - Postinfarction exercise testing. PMID- 8496551 TI - [Values and complications of peripheral deepenings in radial keratotomies]. AB - Single and double peripheral deepenings were used to increase the refractive effect of radial keratotomy (RK). The objective of this study was to statistically evaluate the effect and the complications of these surgical techniques. Simple and double peripheral deepenings were performed in 36 patients (52 eyes) and 14 patients (19 eyes) respectively. The functional results and the complications in these two groups were statistically compared with those of a control group which was comparable according to criteria of size, age, sex and preoperative myopia. The standard RK surgical technique was used in this control group. The difference of mean gain between the control group, and the single and double peripheral deepening groups, was 0.53 and 0.47 diopter, respectively. This difference was statistically significant. On the other hand there was no significant difference diopter gain between the single and the double peripheral deepening groups. There was a significant difference concerning spherical equivalent. The non corrected visual acuity was significantly higher in the peripheral deepenings groups, probably due to corneal topographic alterations generating multifocal corneas. The complication rate (micro-perforations, induced astigmatism, loss of best corrected visual acuity) was higher in the peripheral deepenings groups. The limited diopter gain (about 0.50 diopter) compared with the standard radial keratotomy surgical technique, the lack of decreased, reoperation rate and the increased rate complication justified peripheral deepenings surgery technique discussed by the authors. PMID- 8496552 TI - [Use of diode laser in transcleral retinal photocoagulation]. AB - Transscleral retinal photocoagulation using a diode laser emitting infrared radiation (810 nm) was performed on 8 rabbits. Examination was performed at 2 days, one month and three months after photocoagulation. The retinal burns were examined by light and electron microscopy and were found to be similar to those produced by argon and krypton photocoagulations. Histopathologic evaluation of the lesions demonstrated an intact sclera overlying the chorioretinal lesions. The results of the present experimental study support the hypothesis that transsccleral retinal photocoagulation using diode laser in selected indications may be a valuable alternative to cryotreatment and diathermy in the human eye. The absence of scleral damage and pigmented epithelium cell dispersion as well as the decreased break down of the blood ocular barrier after transscleral diode laser photocoagulation are the main advantages of the technique as compared to transscleral diathermy and cryotreatment. PMID- 8496553 TI - [Disciform keratitis and Kawasaki's disease]. AB - Kawasaki's disease is a mucocutaneous lymph node syndrome associated with an acute febrile illness affecting children. Ocular signs are a principal presenting feature with hyperhemic indurated limbal sparing inflammation (88 to 96%), and some mild anterior uveitis. We report a case of disciform keratitis affecting a 10 year old child. Ocular features of Kawasaki's Disease resolved completely within a few weeks. PMID- 8496554 TI - [Congenital retinal arteriovenous fistula and central retinal vein occlusion]. AB - The authors report a case of congenital arteriovenous communication of the retinal near the macula, associated with a central retinal vein occlusion. This occlusion only affected the inferior half-retina, especially the area surrounding the arteriovenous anastomoses. Laser photocoagulation was applied to areas of peripheral ischemia. After a 12 month follow-up, a marked decrease of visual acuity occurred, attributable to severe ischemia and edema in the posterior pole. An extension of the peripheral capillary non perfusion required additional laser treatment. We also observed the reduction in caliber of the arteriovenous anastomosis. The association of congenital arteriovenous communication and retinal vein occlusion is rare. The clinical and pathogenic features are discussed. Photocoagulation of extensive peripheral capillary occlusion is recommended in order to prevent neovascular complications. PMID- 8496555 TI - [Palpebral nodule with focal madarosis: neoplasm or chalazion? Apropos of a case]. AB - A palpebral tumor associated with focal madarosis and no improvement to medical treatment may suggest a malignant neoplasm. Surgical excision of such a lesion was performed in a 56-year-old male and the histopathologic examination revealed a chalazion. Many similar clinical aspects between palpebral neoplasms and chalazions as well as a high frequency of chalazions secondary to palpebral neoplasms justify surgical excision with an obligatory histopathologic examination. PMID- 8496556 TI - [Physiopathological bases of the treatment of pterygium]. PMID- 8496557 TI - [Chronic corneal ulcer complicated by corneal perforation. Procedure to follow when corneal grafts are not available]. PMID- 8496558 TI - [Is there a relation between cataract and retinopathy in diabetics?]. PMID- 8496559 TI - [Malignant melanoma of the choroid in vivo. Comparative biometry using RX scanner and MRI]. AB - Uveal melanomas are unique among the malignant tumors of the eye investigated by MRI in that both T1 and T2 are relatively shortened due to the paramagnetic effect of melanin. Bearing in mind this property, we conducted a comparative study between MRI and CT in 11 patients with histologically proven choroidal malignant melanoma. The results of this study confirm that MRI is far superior to CT in both differential diagnosis and in determining the extent of the tumor which is crucial if conservative treatment is to be undertaken. PMID- 8496560 TI - [Ultrastructural study of human cornea preserved in organ culture media at +31 degrees C]. AB - Organ culture becomes a standard method of corneal graft preservation. The aim of the study was to evaluate the preservation injuries induced by organ culture. We examined 12 organ cultured human corneas. Corneas were preserved in the medium for 2 to 21 days. Corneas showed some abnormalities: numerous light vacuoles, mitochondrial swelling and increased cell thickness in all cells of the cornea, sloughing of the external and medium epithelial cell layers. We observed normal endoplasmic reticulum, Golgi apparatus and nucleus. These preservation injuries are moderate and reversible. PMID- 8496561 TI - [Retinal detachment following posterior capsulotomy using Nd:YAG laser. Retrospective study of 144 capsulotomies]. AB - Nd:YAG capsulotomy is currently performed after extracapsular cataract surgery and seems to increase the risk of postoperative retinal detachment. In order to evaluate the incidence of this complication in our experience, we retrospectively studied 144 patients who underwent Nd:YAG laser posterior capsulotomy with at least a six-month follow-up. Six patients out of 144 (4.16%) subsequently developed rhegmatogenous retinal detachment. The average time from extracapsular cataract surgery to YAG capsulotomy was 21 months (11 to 26 months). The average time from capsulotomy to retinal detachment was 3.6 months (1 to 8 months). In 4 out of 6 eyes, at least one risk factor for retinal detachment was present (myopia, lattice degeneration, retinal detachment in the fellow eye). Vitreous cells were observed in 4 patients after capsulotomy. In 2 patients, a prophylactic laser photocoagulation had been previously performed. These retinal detachments were not different from aphakic or pseudophakic detachment, but the examination of retinal periphery was particularly difficult because of the peripheral capsular fibrosis, hiding retinal tears in 4 eyes. Two cases of moderate proliferative vitreoretinopathy were observed. Retinal reattachment surgery was successful in all cases with one procedure. The YAG laser energy required to create a capsulotomy was less than that reported in the literature, and no relationship could be established with the total energy applied. Nd:YAG capsulotomy seems to moderately increase the risk of retinal detachment, especially in myopic patients. The mechanisms of vitreous and retinal damage after Nd:YAG capsulotomy are discussed. PMID- 8496562 TI - [Results of reoperation for under correction of radial keratotomies. Apropos of 25 cases]. AB - Twenty-two under corrected patients (25 eyes) after radial keratotomy, were reoperated according to the Stan Franks surgical technique. The results and the possible factors of predictability of this method of reoperation were evaluated. The residual myopia was less than one diopter in 88% of cases (20% before reoperation). The non corrected visual acuity was superior or equal to 20/40 in 88% of cases (32% before reoperation). The mean dioptrie gain after reoperation was 1.30 diopters. Statistical analysis showed that the refractive gain significantly increased with: the initial residual myopia, the delay between the first radial keratotomy and the reoperation, the number of incisions concerned. Age, sex, corneal thickness, initial protocol and presumed cause of undercorrection were not correlated to the refractive gain. (concerning the mean dioptrie gain). The comparison between data derived from different studies, showed no significant differences between the techniques of reoperation. Induced astigmatism with loss of best corrected visual acuity in 12% of cases was the main complication. The causes of under correction after radial keratotomy, and the effectiveness of the Stan Franks method of reoperation are discussed. The authors emphasize the interindividual corneal reaction to radial keratotomy. PMID- 8496563 TI - [Radial keratotomy. Optical and functional results after a 5-year postoperative period]. AB - The authors report a retrospective study of R.K. surgery performed on 72 eyes for simple myopia by one surgeon, five years after surgery. Fifty-four cases were observed regularly at 1 year and 5 years post-operatively, which allowed an analysis of refractive and visual parameters, for myopias between-1.5 and 6 D before surgery. Five years after: 92.9% of eyes were within +/- 1 D of emmetropia; 5.7% of eyes were undercorrected by more than 1 D; 1.4% of eyes were overcorrected by more than 1 D and 88.7% of the cases had uncorrected visual acuity of 20/40 or more. In general, our refractive and keratometric results were stable between the first and fifth year post-operatively. We report only one case of real undercorrection, and one case of progressive hyperopia with loss of best spectacle corrected visual acuity. In this study, we observed a statistically significant decrease of 1/100 in the mean uncorrected visual acuity, which is explained by remyopisations. All but one of them were less than 1 D. The review of long term results of R.K. is difficult because of the many different methodologies and protocols. However all of them show a unpredictable continuous increase in the effect of surgery in the hyperopia direction. Prolonged wound healing seems to be the most probable reason for this progressive hyperopia. PMID- 8496564 TI - [Failures of the surgical treatment of rhegmatogenous retinal detachment]. AB - The surgical treatment of rhegmatogenous retinal detachment, has considerably improved. But there are still a lot of failures, at least after the first surgical procedure. Out of a group of 320 retinal detachments, a one stage surgical procedure allowed the retina to reattach in 84% of cases. Out of the 51 failures, we defined 2 subgroups: the early recurrences were mainly caused by undiagnosed breaks or insufficient scleral buckling, and the delayed recurrences by a vitreo-retinal proliferation or a new tear. Though a second operation increased the success rate to 97%, it is certainly desirable to lower the failure rate of the first surgical procedure. PMID- 8496565 TI - [Retinal detachment in children]. AB - During the period January 1985-June 1990, 333 cases of retinal detachment were operated. Thirty cases (9%) were children aged between 5 to 15 years. Retinal detachment was due to developmental abnormalities: myopia, retinoschisis, inherited cataract and glaucoma in 71.4%. Ocular trauma was found in 28.5%. Peripheral vitreoretinal degenerations were found in 82.8%. Reattachment of the retina was achieved in 77.1% of cases. Best visual acuity was 0.4 or better in 40.7% of eyes. PMID- 8496566 TI - [Superficial amebic keratitis]. AB - Acanthamoeba keratitis is now a well-known entity. However most studies report deep keratitis. We present 4 cases of superficial amebic keratitis in contact lens wearers. Clinical aspects were linear, polymorphous alterations of the corneal epithelium. All patients healed with a combination of debridement of the epithelial lesions and Brolene eye drops. Our cases demonstrate that early diagnosis with early treatment allow healing of superficial amebic keratitis. PMID- 8496567 TI - [Traditional treatment of cataract in Niger. Apropos of 22 cases]. AB - Empiric treatment of cataracts by couching is still commonly performed by traditional healers in West Africa. In the ophthalmology department in the regional hospital of Zinder, in Niger, 22 cases have been identified and their complications treated medically and surgically. The semiotic analysis demonstrated the diversity of methods used, sometimes successfully by the traditional healers. Apart from the classical technics of luxation in the vitreous, we have observed a number of cases with integrity of the posterior capsule and disappearance of the nucleus. These last observations have lead us to believe that certain traditional healers may use local plants with phakolytic effects in their pharmacopia. PMID- 8496568 TI - [Chlamydia trachomatis conjunctivitis in adults. Study of diagnostic techniques]. AB - The place of Chlamydia trachomatis in acute or chronic conjunctivitis is certainly underestimated due to the difficulties involved in the diagnosis. Three diagnostic techniques for Chlamydia trachomatis conjunctivitis were compared: conjunctival sac swab for ELISA technique, scraping of the tarsal conjunctiva for direct immunofluorescence and for culture. Two groups of patients were studied: 73 patients with acute or chronic conjunctivitis and 44 asymptomatic patients. 19.2% of the patients in the first group had a positive result with the two techniques and 6.8% of the patients in the second group also had positive results with the same criteria. Our results show that indirect immunofluorescence is the technique most frequently positive, followed by ELISA, while culture remains the most specific but the least sensitive technique. The existence of healthy carriers Chlamydia trachomatis is demonstrated. PMID- 8496569 TI - [Malignant melanoma of the choroid associated with neurofibromatosis]. AB - A sixteen-year-old white girl with peripheral neurofibromatosis (NF1), who had been treated for a glioma of the optic nerves and chiasma developed a choroidal mass in her only functional eye. After a transchoroidal biopsy, the pathologic examination disclosed a choroidal melanoma of epithelioid cell type, using morphological criteria as well as an immunohistochemical study. After treatment with a ruthenium plaque, the tumor completely regressed over 4 months. According to the data of the literature, neurofibromatosis seems to predispose to the development of uveal melanomas. PMID- 8496570 TI - [Chronic blepharoconjunctivitis during a treatment with acitretin (Soriatane)]. AB - We report external ocular side effects after treatment with acitretin, a new synthetic vitamin A analogue and the main metabolite of etretinate. A patient treated with 20-25 mg/day of acitretin for psoriasis suffered from chronic blepharoconjunctivitis. Schirmer tests, tear lysozyme were normal while rose bengal and fluorescein staining disclosed epithelial punctate defects and tear break-up time was shortened. Meibomian glands of the lower lid were photographed with transillumination and appeared atrophic. Conjunctival cytology and biopsy showed snake-like chromatine appearance, keratinized epithelial cells and some lymphocytes infiltrates. Accessory salivary gland histological aspects were nonspecific. There was a clear relationship between restarting the acitretin therapy and recurrence of ocular symptoms. Acitretin, like other retinoids, may induce or exacerbate blepharoconjunctivitis in patients with psoriasis. PMID- 8496571 TI - [Cavernous hemangioma of the orbit]. AB - Cavernous hemangioma is one of the commonest primary orbital tumors. Painless and progressive reducible unilateral proptosis causing a variable degree of hyperopia is the usual clinical presentation. The case of a 39-year-old-female patient is reported. The clinical presentation was unilateral left axial proptosis with acquired hyperopia. Imaging studies showed a well circumscribed mass in the orbit, a superior neuro-surgical approach allowed complete resection of the tumor, and histopathology revealed the diagnosis of cavernous hemangioma. PMID- 8496572 TI - [urgical technique in radial keratotomy in practice]. PMID- 8496573 TI - [Primary and secondary edematous corneal dystrophies]. PMID- 8496574 TI - [How to treat band keratopathy]. PMID- 8496575 TI - Cost improvement through prudent infection control in a Brazilian hospital. PMID- 8496576 TI - Universal precautions kit. PMID- 8496577 TI - Classification of the surgical wound: a time for reassessment and simplification. PMID- 8496578 TI - Validation of surgical wound classification in the operating room. AB - OBJECTIVE: To determine the accuracy with which circulating nurses (CNs) classify surgical procedures by risk of contamination in the operating room. DESIGN: Classification of surgical procedures by CNs was compared with the classification of surgical procedures by a physician observer. SETTING: University-affiliated, tertiary care hospital. METHODS: Circulating nurses used the traditional wound classification system of clean, clean-contaminated, contaminated, and dirty infected to classify surgical wounds in the operating room. A physician remained in the operating room throughout each of 100 surgical procedures and simultaneously classified surgical wounds without the knowledge of the CNs. RESULTS: Classification of surgical wounds by CNs was compared with classification by the physician observer for 50 cases in general surgery and 50 cases in trauma surgery. Compared with the physician observer, the overall accuracy of classification by CNs was 88% (95% confidence interval [CI] of 81.6% to 94.4%; Kappa statistic, 0.83). Classification of surgical wounds was more difficult in trauma surgery (accuracy of 82%) than in general surgery (accuracy of 94%). Accuracy increased for both services when surgical wounds were classified into just two categories (clean or clean-contaminated versus contaminated or dirty-infected). CONCLUSIONS: Surgical wounds can be classified in the operating room with a high degree of accuracy by CNs. Classification was more difficult in trauma than in general surgery, but classification in trauma surgery improved with feedback to and additional education of CNs. The accuracy of classification by CNs was even higher when classifications were divided into just two categories. PMID- 8496579 TI - Oxacillin- and quinolone-resistant Staphylococcus aureus in Sao Paulo, Brazil: a multicenter molecular epidemiology study. AB - OBJECTIVE: To investigate the possibility of interhospital spread of multiresistant Staphylococcus aureus in Sao Paulo, Brazil. DESIGN: We evaluated 13 nosocomial S aureus strains selected because of resistance to oxacillin and ciprofloxacin. SETTING: The strains were collected between March 1991 and September 1991 from four different hospitals in Sao Paulo. Two were teaching hospitals, and two were private hospitals. PATIENTS: Each strain was isolated from a different patient. All patients were hospitalized when the strains were isolated. INTERVENTIONS: The strains were typed by restriction endonuclease analyses of plasmid DNA (REAP) using EcoRI, HindIII, RsaI, and AluI and by extended antibiogram profile (34 drugs). RESULTS: All strains had identical plasmid and antibiogram profile. They demonstrated the same plasmid pattern as previously described in one of the hospitals studied. CONCLUSIONS: Our results suggest the dissemination of a unique oxacillin- and quinolone-resistant strain of S aureus in several hospitals of Sao Paulo, Brazil. PMID- 8496580 TI - A cluster of surgical wound infections due to unrelated strains of group A streptococci. AB - Group A streptococci account for less than 1% of all surgical wound infections but are an important cause of nosocomial outbreaks. We report here a cluster of four group A streptococcal infections that occurred within an 11-day period on a single surgical service. The index case presented with toxic shock-like syndrome. Epidemiologic investigation did not identify any relationship between infections. Restriction endonuclease analysis and M and T typing found the four isolates to be unrelated. Restriction endonuclease analysis is a useful tool for determining relatedness of nosocomial isolates of group A streptococci. PMID- 8496581 TI - Brucellosis among hospital employees in Saudi Arabia. AB - OBJECTIVE: To report experience with brucellosis among expatriate hospital employees in an area of the world where brucellosis is endemic. DESIGN: Review of cases from the viewpoints of direct supervisor and treating physician, including epidemiologic interviews and clinical follow-up. SETTING: Tertiary care hospital center in a developing country that increased from 125 beds to 450 beds during the period studied. PATIENTS: Employees with clinical findings suggesting brucellosis and in whom a positive blood culture or significantly elevated serologic test confirmed the diagnosis. RESULTS: Nine hospital employees from nonendemic areas developed brucellosis. Five were from England and four from North America. Seven were bacteriology technologists, one was a nurse, and one was an obstetrician. Each had an acute febrile illness with malaise, arthralgia, or headache. Brucella titers were > or = 1:1,280. Five were bacteremic with positive Brucella cultures. All responded to anti-Brucella therapy. Three patients had relapses, but there were no complications. CONCLUSIONS: Among Saudi patients, brucellosis is generally attributable to drinking infected milk or contacting infected animals. On the other hand, among expatriate hospital employees, the infection is likely due to processing Brucella cultures or dealing with infected body fluids. In 1988, the laboratory began stricter infection control measures. Since then, there has been only one case of brucellosis among the hospital employees. PMID- 8496582 TI - Wash hands, disinfect hands, or don't touch? Which, when, and why? PMID- 8496583 TI - Efficacy of chemical sterilants/disinfectants: is there a light at the end of the tunnel? PMID- 8496584 TI - The Agency for Healthcare Policy and Research. PMID- 8496585 TI - Rhodococcus. PMID- 8496586 TI - CD22, a B cell-specific receptor, mediates adhesion and signal transduction. PMID- 8496587 TI - Dipeptidyl peptidase I is enriched in granules of in vitro- and in vivo-activated cytotoxic T lymphocytes. AB - Recent studies have suggested that dipeptidyl peptidase I (DPPI) is the major post-translational processing enzyme responsible for generating activated myeloid and lymphoid granule serine proteases. The current studies assessed the relative levels of DPPI and granzyme A (BLT esterase) in B6 anti-H-2d-specific CTL generated in mixed lymphocyte cultures (in vitro-activated CTL), by infusion of B6 spleen cells into irradiated H-2d mice (graft-vs-host, GVH CTL) or by 1 degree and 2 degrees peritoneal immunization of B6 mice with P815 (H-2d) cells (PE CTL). In contrast to low levels of DPPI activity in unstimulated CD4+ spleen T cells, both unstimulated CD8+ spleen T cells and in vitro-activated CTL populations were several-fold enriched in DPPI activity, while PE CTL and GVH CTL expressed even higher levels of DPPI. Depletion of DPPI-enriched cells by treatment with Leu-Leu OMe resulted in loss of cytolytic effector function from each CTL population. However, PE CTL and GVH CTL were more sensitive to the toxicity of Leu-Leu-OMe than were in vitro-activated CTL. While standard BLT esterase assays detected much higher levels of this serine protease activity in GVH CTL or in vitro activated CTL than in PE CTL, levels of BLT esterase activity significantly above the basal levels present in unstimulated CD8+ or CD4+ T lymphocytes were found in association with immunoreactive granzyme A in lysates of PE CTL. In both PE CTL and in vitro-activated CTL, DPPI and BLT esterase activity co-localized in the granule fraction of cell lysates, and similar percentages of total cellular BLT esterase and DPPI were exocytosed upon cross-linking of surface CD3. Thus, both in vivo- and in vitro-activated CTL were found to possess functional granules containing readily detectable albeit somewhat different levels of DPPI and granzyme A activity. PMID- 8496588 TI - Mixed haplotype A beta Z/A alpha d class II molecule in (NZB x NZW)F1 mice detected by T cell clones. AB - We have tried to demonstrate the existence of a mixed haplotype MHC class II molecule in (NZB x NZW)F1 (B/WF1) mice. When a large panel of keyhole limpet hemocyanin-specific T cell clones derived from B/WF1 mice was analyzed, several clones were shown to be restricted by a F1-specific A beta Z/A alpha d class II molecule. Autoreactive A beta Z/A alpha d-specific T cell clones were also obtained. The ability of the association and expression of A beta Z with A alpha d was confirmed by hybridoma and transfection experiments. Hybridoma cell lines created by fusion of NZW (H-2z) spleen cells with M12.C3 (a A beta d- variant cell line derived from M12.4.1 (H-2d) B lymphoma) cells expressed A beta Z determinants. Transfection of A beta Z genomic DNA to M12.C3 cells resulted in the expression of A beta Z determinants. These hybridoma cell lines and transfectants were able to stimulate A beta Z/A alpha d-specific T cell clones, suggesting the expression of A beta Z/A alpha d molecules on the cell surface. However, attempts to demonstrate the existence of mixed haplotype MHC class II molecules in B/WF1 mice by two-dimensional (nonequilibrium pH gradient gel electrophoresis/SDS-PAGE) gel electrophoresis analysis with the use of anti-class II mAb failed to demonstrate the existence of mixed haplotype A beta Z/A alpha d or A beta d/A alpha z class II molecules in B/WF1 mice. Analysis of mixture of TA beta Z cell and B/WF1 spleen cell lysates immunoprecipitated by anti-A beta Z mAb suggested that the amount of haplotype mixed A beta Z/A alpha d molecules in B/WF1 spleen cells is less than 1/10 that of haplotype matched A beta/A alpha pairs. Our results suggest that, although undetectable by biochemical analysis, small amounts of mixed haplotype A beta Z/A alpha d molecules exist in B/WF1 spleen cells. Also, T cell clones which recognize them exists in B/WF1 mice. Because autoimmune symptoms of B/WF1 mice are shown to be related to heterozygosity at the H-2 region, autoreactive T cell clones which recognize the mixed haplotype A beta Z/A alpha d class II molecule might be involved for the induction of autoimmunity in B/WF1 mice. PMID- 8496589 TI - Activation of CD8-dependent cytotoxic T lymphocyte adhesion and degranulation by peptide class I antigen complexes. AB - Activation of CTL requires engagement of both the TCR and the CD8 coreceptor. Immobilized class I proteins and in vitro-formed peptide class I Ag complexes have been used to examine the relative contributions of TCR and CD8 to the adhesion and response of cloned, class I-restricted CTL. The extent of degranulation was found to be directly proportional to the concentration of peptide used to pulse class I, suggesting that activation is a direct function of TCR occupancy level. In contrast, activation of degranulation as a function of the amount of class I on the surface displayed a marked threshold density dependence. Essentially the same density dependence was found for the response of CTL to fluid phase anti-TCR mAb and non-Ag class I, indicating that CD8-class I interaction must exceed a threshold before effective cosignaling can occur. Adhesion and degranulation of CTL was minimal in response to in vitro peptide class I complexes prepared at a class I density below the threshold. However, the same density of peptide class I initiated both adhesion and response if additional non-Ag class I was coimmobilized on the same surface at levels above threshold. Thus, when surface levels of peptide class I complex are low, as is likely to be the case under physiologic conditions, the level of TCR occupancy achieved is, by itself, insufficient to mediate cell adhesion or activate degranulation. The results demonstrate, however, that low TCR occupancy is sufficient to provide the signal to prime CD8. Provided that the surface density of class I is sufficiently high, CD8 then mediates strong adhesion and provides the costimulatory signal(s) to activate response. PMID- 8496590 TI - Response of human NK cells to IL-6 alterations of the cell surface phenotype, adhesion to fibronectin and laminin, and tumor necrosis factor-alpha/beta secretion. AB - In vitro effects of human recombinant IL-6 (1-1000 U/ml) on highly enriched human NK CD3-CD56+ cells (94% +/- 2; mean +/- SEM; n = 8), obtained from PBL were studied. IL-6 induced low levels of NK cell proliferation (7- to 30-fold during 6 day incubation), which was IL-2-independent, because IL-6 did not induce detectable IL-2 production by NK cells. Two-color flow cytometry analysis demonstrated that incubation of NK cells with IL-6 at the optimal concentration of 250 U/ml for 6 days significantly increased the proportion of NK cells expressing the following activation Ag: CD25 (26% +/- 17, mean +/- SEM vs 4% +/- 1 in control, n = 5), CD54 (44% +/- 17 vs 9% +/- 3), HLA-DR (29% +/- 13 vs 12% +/ 4), CD69 (45% +/- 7 vs 12% +/- 3), and CD71 (34% +/- 17 vs 6% +/- 2). The mean fluorescence intensity of these activation Ag was increased as well. IL-6 induced expression of CD49b (alpha-chain of VLA-2, 20% +/- 11 vs 2% +/- 1) and CD49c (alpha-chain of VLA-3, 43% +/- 17 vs 5% +/- 3), which are not expressed on resting NK cells. IL-6 also enhanced the fluorescence intensity of beta 1 integrins, CD49d, CD49e, and CD49f, expressed on NK cells. IL-6-stimulated NK cells showed significantly increased integrin-mediated adhesion to fibronectin- or laminin-coated plates (26 +/- 3 mean % cells adhering +/- SEM vs 15 +/- 4 in control for FN and 19 +/- 1 vs 11 +/- 1 for LM, p < 0.05 for both) as determined in a 3 h binding assay. As assessed by inhibition of adhesion using mAb to the VLA-2, -3, -4, -5, and -6, NK cell adhesion to fibronectin was mediated by VLA-4 and 5, and their adhesion to laminin by VLA-3 and -6. NK cells incubated in the presence of IL-6 were found to produce a factor cytostatic to WEHI-164 clone 13 target cells. This effect was partly, although significantly, blocked by neutralizing antibodies to TNF-alpha or TNF-beta. Our data demonstrate that IL-6 can directly activate human NK cells, but is a less potent NK cell activator, for all activation and functional parameters studied, than IL-2. PMID- 8496591 TI - Liver gamma delta T cells. TCR junctions reveal differences in heat shock protein 60-reactive cells in liver and spleen. AB - The liver of mice contains elevated percentages of gamma delta T cells when compared with peripheral lymphoid organs. We have now analyzed these cells clonally, by generating a random collection of liver gamma delta T cell hybridomas and sequencing the productively rearranged TCR-gamma and -delta genes in each hybridoma clone. Examining C57BL/10 mice of various ages, we have found that over half of their normal gamma delta T cells are one of two types, V delta 4+ or V delta 6.3+. gamma delta T cell hybridomas generated from mouse liver contain clones that are "spontaneously" reactive, and respond to purified protein derivative from mycobacteria and to a 17-amino acid peptide from mycobacterial heat shock protein-60 (HSP-60). Like similar cells found in newborn thymus or adult spleen, all of the cells showing this HSP-60 reactivity pattern were found to express V gamma 1-J gamma 4-C gamma 4, most in conjunction with V delta 6-J delta 1-C delta, particularly with V delta 6.3. However, the gamma and delta junctional sequences of the V gamma 1/V delta 6+ cells isolated from adult liver differed from those found in adult spleen; being less diverse, their receptors instead resemble those of similar cells from newborn thymus. These data suggest that HSP-60-reactive gamma delta cells in adult murine liver and spleen are independent of each other and may be resident in their respective sites. PMID- 8496592 TI - Rejection of an IA+ variant line of FBL-3 leukemia by cytotoxic T lymphocytes with CD4+ and CD4-CD8- T cell receptor-alpha beta phenotypes generated in CD8 depleted C57BL/6 mice. AB - FBL-3N is an MHC class II Ag+ variant line that was obtained spontaneously during maintenance of Friend virus-induced leukemia FBL-3 in an athymic C57BL/6 (B6) mouse. Inocula of FBL-3N, but not the parental FBL-3 tumor, regressed after initial growth in CD8-depleted, syngeneic B6 mice. The cellular mechanisms by which FBL-3N was rejected in these mice were investigated in this study. We demonstrated that CTL with both CD4+ and CD4-CD8-TCR-alpha beta phenotypes were generated in mixed lymphocyte tumor cell culture spleen cells obtained from CD8 depleted B6 mice that had rejected FBL-3N by in vitro stimulation with mitomycin C-treated FBL-3N. After adoptive transfer of these CTL that were generated in vitro into athymic B6 mice, challenge with the FBL-3N tumor resulted in tumor regression after its initial growth. Thus, CD4+ and CD4-CD8-TCR-alpha beta CTL mediated rejection of the FBL-3N tumor in CD8-depleted B6 mice. Furthermore, the findings that depletion of B6 mice of CD4+ cells in addition to CD8+ cells abrogated the rejection of FBL-3N and generation of CTL in mixed lymphocyte tumor cell culture spleen cells suggest that CD4+ cells were required not only as a source of CD4+ CTL, but also as helper cells for generation of CD4-CD8-TCR-alpha beta CTL. Tumor Ag recognition of CD4-CD8-TCR-alpha beta CTL was restricted to Db, like that of classical CD8+ CTL, but the restriction appeared to be less obligatory than that of CD8+ CTL. PMID- 8496593 TI - HB4 antibody recognizes a carbohydrate structure on lymphocyte surface proteins related to HB6, CDw75, and CD76 antigens. AB - Cells regulate the specificity of the carbohydrate chains on their membrane-bound glycoconjugates by differential expression of glycosyltransferases. In lymphocytes, beta-galactoside alpha 2,6-sialyltransferase is reportedly involved in the generation of epitopes recognized by HB6, CDw75, and CD76 mAb. The HB4 mAb binds to an Ag present on subpopulations of B and NK cells. We now show that this Ag represents another member of a set of neuraminidase-sensitive, alpha 2,6 sialyltransferase-generated sugar Ag. Transient expression of a cDNA encoding this enzyme in COS cells generated a minor population of HB4+ cells that was completely contained within the HB6+ COS cell population. Using various proteinases and an inhibitor of N-linked carbohydrate processing, we show both epitopes to represent components of N-glycosylated membrane proteins. Remarkably, porcine thyroglobulin, an alpha 2,6-NeuAc+ glycoprotein, is specifically recognized by both mAb. These data underline a close relationship between HB4 and HB6 epitopes and imply further that both mAb react with oligosaccharide chains irrespective of the carrier molecule nature. Thus, the terminal sugar residue sialic acid plays a pivotal role in at least four distinct epitopes that are expressed differentially in immune cells. This may point at an important role for these epitopes in biologic recognition. PMID- 8496594 TI - Expression cloning of the early activation antigen CD69, a type II integral membrane protein with a C-type lectin domain. AB - CD69 is a very early activation Ag of T lymphocytes. It is a cell surface glycoprotein that can only be detected after stimulation of lymphocytes. Despite extensive studies on its biologic activities, little is known about its molecular function. To investigate the latter in more detail, we have cloned a cDNA encoding CD69 on the basis of its expression in COS cells. The nucleotide sequence of clone CD69.13 is 1676 bp in length and contains a single open reading frame of 600 bp encoding a protein of 199 amino acids. The predicted molecular mass of 22,559 Da could be confirmed by in vitro translation. The protein contains a hydrophobic transmembrane region between amino acids 41 and 61 but no N-terminal signal peptide, which suggests that it is a type II membrane protein. It has one potential N-glycosylation site at amino acid 166. Two glycosylated forms of 26 to 28 kDa and 32 to 34 kDa were detected both in transfected COS cells and in in vitro translation in the presence of canine microsomes. Proteinase K degradation of the N-terminal part after in vitro protein synthesis supports the view of CD69 being a type II integral membrane protein with the N terminal 40 amino acids in the cytoplasm, a transmembrane domain of 21 amino acids, and C-terminal 138 amino acids as the extracellular domain. Homology searches revealed sequence similarity with members of a supergene family of type II integral membrane proteins with a C-type lectin domain, indicating that CD69 is involved in signal transduction. PMID- 8496595 TI - Developmental and cytokine-mediated regulation of MHC class II gene promoter occupancy in vivo. AB - The class II genes of the major histocompatibility complex are a family of genes whose expression is regulated developmentally in cells of the B lineage and by IFN-gamma in many other cell types. Using the approach of in vivo footprinting, which allows for the examination of protein-promoter interactions within intact cells, we demonstrated a transition from unoccupied to occupied to once again unoccupied class II promoters in cell lines representing the developmental pathway of B cells. IFN-gamma treatment of HeLa cells led to increased promoter occupancy of the DR alpha and DR beta promoters at the same sites that are constitutively bound in mature B cells. No IFN-gamma-specific binding site was induced. Additionally, an octamer element in the DR alpha gene displayed preferential binding in B cells. These results demonstrate that changes in the transcription of the class II genes are associated with changes in factor binding at the promoter in vivo. Moreover, given the ubiquity of class II promoter binding proteins, these results suggest that throughout B cell development and upon IFN-gamma stimulation, the accessibility of class II promoter DNA is subject to regulation. PMID- 8496596 TI - Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. AB - Anti-DNA antibodies have been successfully induced in normal, nonautoimmune mice by immunization with complexes formed with a DNA-binding peptide, Fus1, and native, B form, mammalian DNA. Fus1 is a 27-amino acid peptide from the internal domain of a ubiquitin fusion protein from Trypanosoma cruzi. The structure of this peptide is homologous to the consensus amino acid sequence for a DNA binding, "zinc finger" motif, and the peptide binds to DNA. A panel of six anti DNA antibody-producing hybridomas, two IgM and four IgG2a, have been generated from a single BALB/c mouse immunized with Fus1-DNA. The V region structures for both H and L chains of the induced anti-DNA antibodies are highly homologous if not identical to the V region structures of spontaneous anti-DNA antibodies from autoimmune (NZB x NZW)F1 mice. The DNA specificities of the anti-DNA antibodies were also similar to those of autoimmune anti-DNA antibodies. Three of the four induced IgG antibodies bound equally well to native and denatured DNA. These results demonstrate that antibody specific for nDNA can be induced with immunogenic complexes of native DNA. They also demonstrate that monoclonal representatives of the induced anti-DNA antibodies have serologic and structural characteristics similar if not identical to those of spontaneous anti-DNA antibodies from autoimmune mice. The experimental system described here should provide insight not only about the structural basis for autoimmunity to DNA but also the function of anti-DNA antibody in the immunopathology of SLE. PMID- 8496597 TI - Differential action of cycloheximide and activation stimuli on transcription of tumor necrosis factor-alpha, IL-1 beta, IL-8, and P53 genes in human monocytes. AB - In the present study we have analyzed superinduction of TNF-alpha mRNA and enhancement of TNF-alpha gene transcription by cycloheximide (Chx) in human blood monocytes isolated by continuous Percoll gradient and activated in vitro. In the same monocyte cultures, we have compared the rate of gene transcription of TNF alpha, IL-1 beta, IL-8, and the P53-antioncogene under the influence of plastic adherence, Staphylococcus aureus Cowan 1 (SAC), and Chx added at different times of monocyte culture. It was shown that the cytokine genes have low or negligible transcriptional activity in freshly isolated monocytes, whereas P53 gene transcription was constant in freshly isolated and in vitro-stimulated cells. Transcription of the IL-1 beta and IL-8 genes was induced by adherence and was not more enhanced by SAC. Transcription of the TNF-alpha gene was not induced by adherence. Chx added at the beginning of the monocyte culture did not block TNF alpha or IL-1 beta gene transcription. IL-8 gene transcription, however, was abrogated by Chx. Addition of SAC to monocyte culture containing Chx caused significant enhancement of TNF-alpha gene transcription. Addition of Chx after 2.5 or 4 h of SAC activation caused "superinduction" of TNF-alpha mRNA and enhancement of TNF-alpha gene transcription. The data imply that TNF-alpha gene transcription in activated human monocytes might be regulated by both positive and negative regulatory factors that differ in their stability and protein synthesis dependence. In addition, results demonstrate that TNF-alpha, IL-1 beta, IL-8, and p53 genes in human monocytes are differently regulated. PMID- 8496598 TI - Residues that mediate DNA binding of autoimmune antibodies. AB - Somatic mutations to arginine (R) are a common feature of a subset of J558 H chain genes that code for the majority of high-affinity, anti-dsDNA antibodies in autoimmune MRL/lpr mice. To examine the consequences of such amino acid substitutions on DNA binding, we reverted three somatic mutations of a prototypic anti-dsDNA H chain gene, VH3H9, and assayed the effect of those reversions by expression in a V lambda 1 L chain-only plasmacytoma line. Reversion of R53 eliminated virtually all dsDNA binding and sharply reduced ssDNA affinity. While the complete germ-line revertant of VH3H9 retained a low level of DNA binding, the substitution of R96, a product of N base addition in the third complementarity determining region (CDR3), with glycine (G) was sufficient to abolish measureable DNA specificity. Antibodies with higher affinity for DNA were generated by introducing arginines into VH3H9 at any one of four positions where somatic mutations to arginine had been identified by sequencing other anti-dsDNA J558 H chain genes. All four arginine mutants showed affinity increments consistent with their direct involvement in DNA binding, although one such mutant, K64R, required the simultaneous reversion of an adjacent aspartic acid (D) to the germ-line glycine. Two variants with three nongerm-line arginines showed further improvements in DNA affinity suggesting that their contributions to DNA binding may be additive. Molecular modeling of antibody and mutant F(ab) structures and calculations of their electrostatic potentials were used as an aid in interpreting the results and in predicting the location and size of possible combining sites. PMID- 8496599 TI - Monoclonal, anti-domain and anti-peptide antibodies assign the molecular weight 160,000 granulocyte membrane antigen of the CD66 cluster to a mRNA species encoded by the biliary glycoprotein gene, a member of the carcinoembryonic antigen gene family. AB - mAb directed against the CD66 cluster of granulocyte differentiation Ag recognize Ag of the carcinoembryonic Ag family. A major Ag in extracts from granulocyte membranes bound by CD66 antibodies exhibits a relative molecular mass of 160,000. According to recent data, this Ag may be a product of the biliary glycoprotein (BGP) gene that belongs to the CEA gene family. As a result of alternative splicing, the BGP gene is transcribed into at least seven distinct mRNA species. To identify splice variants of BGP, antisera were raised against the A2 domain expressed in bacteria and to a peptide comprising the C-terminal 23 amino acids encoded by the 3' exon of the BGP gene. The antisera and an mAb specific for members of the BGP family were used to identify potential BGP splice variants in granulocyte membranes. For comparison, the binding of antibodies to Ag purified from human bile was investigated. In the membrane preparation from granulocytes, the only Ag identified by the mAb, the domain antiserum and the peptide antiserum, was the Ag of M(r) 160,000 recognized by a CD66 antibody. These results indicate that the M(r) 160,000 granulocyte membrane Ag of the CD66 cluster is the product of the BGP-specific mRNA containing all coding sequences of the BGP gene. Among two major biliary glycoproteins present in human bile, the M(r) 115,000 Ag contains the A2 domain, whereas the domain is lacking in the "classical" biliary glycoprotein of M(r) 85,000. None of the bile Ag bound the peptide antiserum. PMID- 8496600 TI - Use of the most JH-proximal human Ig H chain V region gene, VH6, in the expressed immune repertoire. AB - VH6, the most 3' human H chain V region gene, is preferentially expressed in the preimmune repertoire of the developing human fetus. To determine whether VH6 contributes to the immune repertoire, we amplified and sequenced from human spleen RNA VH6 rearrangements that were isotype-switched to IgG. Eighteen distinct in-frame VH6 clones were sequenced. Definitive assignment to C gamma 1 could be made in the majority of clones, and all had undergone extensive somatic hypermutation in the V region with an average of 14 (range, 2 to 25) mutations/281 bp in the VH6 segment. The overall frequency of somatic mutation was 5.2% of the total nucleotides sequenced. Replacement somatic mutations were targeted to the complementarity determining region, and the complementarity determining region had higher replacement to silent mutation ratios, consistent with antigenic selection. Silent somatic mutations were also significantly more frequent in the complementarity determining region compared to the framework region. Five clones were derived from the same VH6Dxp'1JH6 rearrangement, each containing unique and shared mutations. All DH segments used by independently arising clones were unique, and all DH reading frames were seen. N segments were lacking at either the 5'DH-JH junction or the 3'DH-JH junction in 7 of 13 independent rearrangements. DH-DH recombinations were frequently observed, and there was biased usage of JH3b and JH4b in the clones. The data imply that a high degree of diversity arises from use of this 3'-VH gene in the immune repertoire. PMID- 8496601 TI - Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. AB - Macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta all belong to the newly recognized "chemokine" superfamily of structurally related, activation-inducible cytokines with inflammatory and growth regulatory activities. We report the isolation and sequencing of genomic clones for murine MIP-2 and murine MIP-1 beta, and analyze their regulatory sequences in comparison with each other and with several other members of the chemokine family. The murine (mu)MIP-2 genomic clone displays the canonical four exon/three intron structure typical of other genes in the chemokine alpha subfamily (e.g., IL-8). Potential cis regulatory elements in the proximal promoter region were highly conserved between muMIP-2 and its three most closely related human homologs: human (hu)GRO-alpha, huGRO-beta, and huGRO-gamma. A mouse macrophage cell line, RAW 264.7, was transfected with a growth hormone reporter construct driven by a proximal fragment of the muMIP-2 5' promoter, and nested deletion mutant analysis localized the LPS responsive element to a region that contains a conserved NF kappa B consensus motif and lies 51 to 70 bp 5' from the transcription start site. In contrast to that of MIP-2, the muMIP-1 beta genomic clone exhibited the three exon/two intron structure characteristic of the chemokine beta family members (e.g., MCP-1). A comparison of the promoters for muMIP-1 beta and muMIP-1 alpha reveals a conserved CK-1 element, but transient expression studies in RAW 264.7 macrophages with proximal fragments of either the muMIP-1 beta or the muMIP 1 alpha 5' promoter fused to a human growth hormone reporter gene link LPS inducibility in both to promoter segments near to, but not identical with, the consensus CK-1 sequence. Proximal 5' promoter fragments cloned from both the MIP 1 alpha and MIP-1 beta genes unexpectedly conferred constitutive expression on the fused reporter gene sequences in macrophage-like cells, but initial 5' deletion analysis did not link this responsiveness to known sequence motifs. The muMIP-1 beta promoter, but not the muMIP-1 alpha promoter, was constitutively active in B16 mouse melanoma cells, and both promoters were active in the myelomonocytic cell line WEHI 3B(A)d-, the muMIP-1 alpha promoter being three times stronger. PMID- 8496602 TI - Genomic structure and chromosomal mapping of the human CD22 gene. AB - The human CD22 gene is expressed specifically in B lymphocytes and likely has an important function in cell-cell interactions. A nearly full length human CD22 cDNA clone was used to isolate genomic clones that span the CD22 gene. The CD22 gene is spread over 22 kb of DNA and is composed of 15 exons. The first exon contains the major transcriptional start sites. The translation initiation codon is located in exon 3, which also encodes a portion of the signal peptide. Exons 4 to 10 encode the seven Ig domains of CD22, exon 11 encodes the transmembrane domain, exons 12 to 15 encode the intracytoplasmic domain of CD22, and exon 15 also contains the 3' untranslated region. A minor form of CD22 mRNA likely results from splicing of exon 5 to exon 8, skipping exons 6 and 7. A 4.6-kb XbaI fragment of the CD22 gene was used to map the chromosomal location of CD22 by fluorescence in situ hybridization. The hybridization locus was identified by combining fluorescent images of the probe with the chromosomal banding pattern generated by an Alu probe. The results demonstrate that CD22 is located within the band region q13.1 of chromosome 19. Two closely clustered major transcription start sites and several minor start sites were mapped by primer extension. Similarly to many other lymphoid-specific genes, the CD22 promoter lacks an obvious TATA box. Approximately 4 kb of DNA 5' of the transcription start sites were sequenced and found to contain multiple Alu elements. Potential binding sites for the transcriptional factors NF-kappa B, AP-1, and Oct-2 are located within 300 bp 5' of the major transcription start sites. A 400-bp fragment (bp 339 through +71) of the CD22 promoter region was subcloned into a pGEM chloramphenicol acetyltransferase vector and after transfection into B and T cells was found to be active in both B and T cells. Further studies of the CD22 gene should lead to a greater understanding of the expression of CD22 during B cell development and differentiation. PMID- 8496603 TI - cDNA cloning of guinea pig monocyte chemoattractant protein-1 and expression of the recombinant protein. AB - Monocyte chemoattractant protein-1 (MCP-1) cDNA was cloned from guinea pig spleen cells stimulated with Con A. The cDNA comprised 647 bp with an open reading frame that encoded a 120 amino acid protein. The sequence similarity of the first 99 amino acids to human MCP-1 is 56%. Recombinant guinea pig MCP-1 was expressed in COS-7 cells, then purified by a three step procedure with orange A-agarose, carboxymethyl-HPLC, and reversed phase-HPLC. The purified protein was found around 25 kDa as a broad band on a polyacrylamide gel under reducing conditions. Guinea pig MCP-1 attracted about 34% of input human monocytes at 5 x 10(-9) M. Guinea pig peritoneal exudate macrophages migrated toward guinea pig MCP-1 dose dependently, but only 1% of input cells responded to guinea pig MCP-1 at its optimal concentration of 5 x 10(-9) M. Human MCP-1 attracted 1% of input guinea pig peritoneal exudate macrophages at its highest concentration of 2.5 x 10(-8) M. Neither human nor guinea pig MCP-1 attracted guinea pig peritoneal resident macrophages. These results suggest that monocytes lose responsiveness to MCP-1 after differentiating to macrophages. Finally, intradermal injection of the recombinant protein into guinea pigs caused marked macrophage infiltration. Cloned and expressed guinea pig MCP-1 will help in studying the role of MCP-1 in vivo. PMID- 8496604 TI - Genetically permissive recognition of adjacent epitopes from the 19-kDa antigen of Mycobacterium tuberculosis by human and murine T cells. AB - The specificity of the T cell-immune repertoire at the level of individual antigenic determinants could play a fundamental role in the immunopathogenesis of tuberculous infections. Therefore, we analyzed the immunogenicity, genetic restriction, and epitope core structure of two adjacent, yet distinct, immunodominant T cell determinants from the 19-kDa Ag of Mycobacterium tuberculosis. After immunization with two peptides comprising residues 45 to 64 and 61 to 80, vigorous in vitro proliferative responses to the homologous peptide were elicited in five different strains of C57BL/10 mice (H-2b,k,d,s,f), indicating that both epitopes were recognized in a genetically permissive manner. When immunized with intact 19-kDa protein, lymph node cells from the same mouse strains responded to both peptides, with the exception of H-2b mice, which did not respond to p45-64. Delayed-type hypersensitivity responses in C57BL/10 (H-2b) mice were elicited by p61-80 only, whereas in H-2d mice both peptides were delayed-type hypersensitivity negative, despite eliciting pronounced proliferative responses. Analysis of the proliferative responses of human PBMC in purified protein derivative-positive healthy subjects and tuberculosis patients revealed significant differences in the antigenicity to the two peptides. All purified protein derivative-positive healthy and diseased individuals manifested strong responses to p45-64, indicating HLA permissive recognition. In contrast, pronounced responses to p61-80 were detected only in patients with lymphatic tuberculosis. Epitope core structures, composed of 6 or 7 residues within each peptide, have been mapped with peptides of overlapping sequence. Significantly, for both epitopes, the core sequences recognized by both human and murine T cells were almost identical. We conclude that despite many similarities between murine and human T cell epitope recognition, distinct differences in the responsiveness of the infected host could play a role in pathogenesis. Furthermore, the genetically permissive nature of the identified epitopes is a potentially important attribute for the development of peptide-based diagnostic reagents and vaccines. PMID- 8496605 TI - Cytokine mediation of the suppressive effect of ferritin on colony-stimulating factor-1-dependent monocytopoiesis. AB - Peptide-specific IgG from a rabbit immunized with an alanine-lysine-proline arginine ((ALA1)-tuftsin) containing 14-mer "ferritin" peptide neutralized rat liver ferritin inhibition of in vitro CSF-1-dependent monocytopoiesis. Antiferritin IgG similarly neutralized the inhibitory effect of ferritin but did not neutralize peptide inhibition of the in vitro myelopoietic response. No cross reactivity between the respective antibodies and Ag was detected either by Western immunoblot or by competitive ELISA. Depletion of adherent cells before marrow cell culture significantly reduced the inhibitory effect of ferritin but did not influence peptide inhibition of CSF-1-stimulated colony formation. Adherent marrow cells and P388D1 cells treated with both CSF-1 and ferritin, but not either alone, produced inhibitory supernatant culture media that were neutralized by antipeptide but not antiferritin IgG. High resolution molecular sieve chromatography of the inhibitory adherent marrow cell and P388D1 supernatants resolved two peaks of 50 to 60 kDa and approximately 30 kDa in each. The inhibitory activity in all four peaks was neutralized by antipeptide but not antiferritin IgG. The ferritin/CSF inhibitors were not further characterized although identity with IL-6, IL-8, TNF-alpha, transforming growth factor-beta, and IFN-alpha/beta could be eliminated. The results indicate that ferritin inhibition of CSF-1-dependent monocytopoiesis is mediated by an endogenously produced inhibitor, or inhibitors, that shares antigenic similarity with the (ALA1)-tuftsin-containing 14-mer peptide and that adherent marrow cells, most likely monocytes or macrophages, produce the endogenous inhibitors in response to both CSF-1 and ferritin. PMID- 8496606 TI - Microvascular effects of complement blockade with soluble recombinant CR1 on ischemia/reperfusion injury of skeletal muscle. AB - Reperfusion of ischemic tissue is associated with tissue injury greater than that resulting from ischemia alone. C activation has been hypothesized to mediate the so-called ischemia/reperfusion injury through both membrane attack and C5a dependent recruitment of neutrophils to sites of C3 fixation on the endothelium via C3 receptors. Adherence of neutrophils is preconditional to expression of their deleterious effects, which are central to the pathophysiology of ischemia/reperfusion injury. This study was designed to evaluate the effect of inhibition of C activation on ischemia/reperfusion injury using a soluble and truncated recombinant human CR1 (sCR1) molecule, a "tail-less" form of the membrane C3b/C4b receptor (CD35) that functions as a regulator of C activation. Capillary perfusion and leukocyte adherence to venular endothelium were measured after reperfusion in a mouse cremaster muscle model that allowed microscopic video observation of microcirculatory changes. Infusion i.v. with sCR1 before a 4 h period of ischemia and during a 3-h subsequent period of reperfusion prevented the increase in leukocyte adherence to venular endothelium seen in controls, and enhanced the number of reperfusing capillaries by 55%. Trypan blue staining showed an increase in muscle cell viability from 11 to 50% in mice receiving sCR1 as compared to controls. Tests of blood samples from mice infused with sCR1 demonstrated nearly complete inhibition of the mouse alternative pathway of C activation, but no detectable loss of the mouse classical pathway of C activation. It was concluded that C activation in this model of skeletal muscle injury is likely to be due to the alternative pathway, and that inhibition of C activation during reperfusion inhibits leukocyte adherence to blood vessel walls and protects the capillary microcirculation. PMID- 8496607 TI - Topical application of T-2 toxin inhibits the contact hypersensitivity response in BALB/c mice. AB - T-2 toxin, a trichothecene mycotoxin, has previously been shown to alter immune functions and promote skin tumors. We demonstrate that topically applied T-2 toxin reduces the ear swelling response to oxazolone challenge in BALB/c mice. For this reduction in ear swelling to occur, toxin application must be at, or within, 1 h after challenge. Dose-response studies showed a 44% reduction in ear swelling with 30 ng of T-2 toxin as compared with a similar reduction with 300 ng of dexamethasone. T-2 toxin did not affect Ag transport from the challenge site to the draining lymph nodes as measured by FITC transport. However, T-2 toxin significantly reduced both MHC class II (Ia) expression and Ag presentation at the same concentrations. Because T-2 toxin, a known protein synthesis inhibitor, was found to inhibit protein synthesis in epidermal cell cultures as measured by [3H]-leucine incorporation, cycloheximide was also examined. Cycloheximide reduced both oxazolone-induced ear swelling and Ag presentation in a similar manner to T-2 toxin. One mechanism of action for T-2 toxin in reducing the contact hypersensitivity response is via inhibition of protein synthesis and effective Ag presentation by epidermal Langerhans cells. This may involve alterations in Ia Ag expression, although a role for class II in the induction phase of the contact hypersensitivity response has not been established definitively. PMID- 8496608 TI - Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple V beta T cell receptor genes. AB - Intestinal intraepithelial lymphocytes (IEL) are a phenotypically distinct T cell population of unknown function. The majority of human intestinal IEL express the TCR-alpha beta, the CD8 accessory molecule, and the CD45RO Ag, suggesting that they are MHC class I-restricted memory T cells. Recent analyses of the TCR alpha- and beta-chains expressed by these cells have shown marked skewing toward one or several V region genes in individual donors and revealed the presence of clonally expanded cells. In addition, functional data has suggested that the MHC class I like CD1 molecules may be the target ligands for some human intestinal IEL clones. This report examines in detail the TCR-beta repertoire of human jejunal IEL to determine what fraction of these cells are clonally expanded and to determine whether a particular subset of V beta genes are utilized by the clonally expanded cells. The results demonstrate that the majority of IEL are derived from the expansion of a relatively few T cell clones and that these clones can utilize a large number of different V beta genes. Oligoclonal expansion is also demonstrated among lamina propria lymphocytes (LPL), with overlapping but distinct clones detected in the LPL vs the IEL populations. These results indicate that most intestinal IEL-alpha beta, and a subpopulation of LPL, are specific for a limited number of Ag and place constraints on the possible roles played by IEL in the defense against diverse environmental pathogens or in the generation of oral tolerance. PMID- 8496609 TI - Expression of the Fc receptor for IgG (Fc gamma RII/CDw32) by human circulating T and B lymphocytes. AB - Tissue-specific isoforms of the human FcR for IgG Fc gamma RII (CDw32) have previously been described by using mAb. These mAb were shown to exhibit different patterns of reactivity with lymphocytes. Among human PBL, Fc gamma RII has been detected on B cells but not T cells when assessed by flow cytometry and microscopy with the use of mAb KB61 and 41H16. Although KB61 and 41H16 were found to react with B cells, the mAb IV.3, CIKM5, and 2E1 did not react with any PBL subset. In this study, we show that KB61 and 41H16 react strongly with the majority (93-96%) of B cells (CD20+), and weakly with a proportion (18-42%) of T cells (CD3+), including 10 to 14% of CD4+ and 27 to 69% of CD8+ cells. In addition, mRNA for Fc gamma RII was detected in purified CD3+CD8high+ lymphocytes by polymerase chain reaction. KB61 and 41H16 also reacted with a majority of CD3 CD16/CD56+ cells, and CD3-CD20- cells. These findings indicate that a subset of T cells and non-T/non-B cells express Fc gamma RII, and are of interest in the light of previous studies which postulate that human Fc gamma R+ cells and Fc gamma RII+ murine T cells suppress the B cell immune response. PMID- 8496610 TI - Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha. AB - To study self reactivity, a transgenic mouse model has been established in which the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) is expressed in the beta-islet cells of the pancreas (rat insulin promoter (RIP)-gp). These mice (H-2b) do not spontaneously develop diabetes; however, infection with the LCMV strain WE rapidly induces hyperglycemia. In this study, comparative analysis of H 2k RIP-gp-transgenic animals demonstrated that the haplotype influences the incidence and kinetics of diabetes and alters the requirement for the CD4+ T cell subset. This study also showed that the properties of the virus expressing the self target Ag determined whether hyperglycemia occurred in RIP-gp-transgenic mice. Various LCMV strains were able to induce diabetes in RIP-gp-transgenic animals, whereas infection with a recombinant vaccinia virus expressing LCMV-gp (vacc-gp) did not induce diabetes. However, vacc-gp could induce diabetes in double (RIP-gp/TCR)-transgenic mice, where the majority of CD8+ T cells expressed a receptor specific for LCMV-gp, suggesting that a critical number of self reactive T cells must be activated to induce disease. Notably, histologic analysis of pancreata taken various days after LCMV or vacc-gp infections indicated that induction of diabetes coincided with an increase in MHC class I expression on the islets of Langerhans. Additional studies with vacc-gp were done to determine other factors that possibly enhance autoimmune attack. Transgenic mice expressing both LCMV-gp and TNF-alpha under the control of the RIP were infected with vacc-gp, and 50% of RIP-gp/TNF-alpha-transgenic animals became hyperglycemic. These data suggest that the increased local lymphocyte traffic as a result of TNF-alpha expression attracts activated gp-specific T cells, enhancing the possibility of hyperglycemia. Collectively, these results demonstrate that the induction of diabetes in this model is influenced by the MHC haplotype, the infectious agent, TNF-alpha expression, the level of MHC class I expression, and the induction of a threshold number of self-reactive CTL. PMID- 8496611 TI - Role of CD25+ and CD25-T cells in acute HIV infection in vitro. AB - T cell activation plays a major role in the ability of the HIV to remain latent or establish a productive infection. The alpha-chain of the IL-2R (CD25, Tac, p55) is expressed on activated but not resting T cells and therefore represents an ideal marker to distinguish activated from resting T cells. The present studies were designed to define the role of CD25+ (activated) and CD25- (resting) T cells in an acute HIV infection in vitro. This objective was accomplished by selectively killing CD25+ cells with an anti-CD25-ricin A chain immunotoxin (RFT5 deglycosylated ricin A (dgA)) either before or after HIV infection, and then determining the effect of eliminating these cells on the secretion of viral p24 Ag. Three major findings have emerged from this study: 1) Elimination of the small population (3 to 5%) of activated, CD25+ cells present in normal PBMC before HIV infection results in a 99% reduction in p24 secretion. 2) RFT5-dgA, an immunotoxin directed against CD25, kills HIV-infected CD25+ cells. Elimination of the CD25+ cells after infection with HIV virtually stops viral production and the spread of the infection in these cultures. This was confirmed by coculturing RFT5 dgA-treated PBMC with H9 cells. 3) When RFT5-dgA-treated PBMC (CD25-cells) were infected with HIV and then activated with a solid phase anti-CD3 mAb, the levels of p24 produced were comparable with those of PBMC from which the CD25+ cells had not been eliminated. Taken together these findings suggest that both activated (CD25+) and resting/quiescent (CD25-) cells can be infected with HIV but that only the CD25+ cells produce viral proteins in the absence of additional activation. PMID- 8496612 TI - Cloned spindle and epithelioid cells from murine Kaposi's sarcoma-like tumors are of endothelial origin. AB - Kaposi's sarcoma (KS) is a complex neoplasm comprising spindle cells, vascular structures, erythrocytes, and an inflammatory infiltrate. The pathogenesis of this disorder is not yet understood, which is a major impediment to the design of safe and effective new therapies. We previously reported a murine model in which simian virus 40 (SV40) T-antigen-transformed murine endothelial cells induce lesions with the histopathologic features of KS. We have now cloned by limiting dilution seven morphologically distinct tumor-derived lines, all of which express the SV40 T antigen. Because SV40 is non-permissive in mouse cells, the presence of this viral marker permits definitive identification of cellular origin. We report here that both spindle cell and epithelioid cell clones from these KS-like tumors are derived from endothelial cells. PMID- 8496613 TI - p53 mutations are common and early events that precede tumor invasion in squamous cell neoplasia of the skin. AB - Mutations of the p53 gene are the most common genetic abnormality described in human cancer; p53 mutations have recently been reported in more than half of the cases of squamous cell carcinomas of the skin. We have previously reported positive p53 immunostaining in Bowen's disease and actinic keratosis. To determine if this abnormal immunostaining reflects p53 mutation or alternative pathways of p53 protein inactivation we have performed direct sequencing of p53 in 20 further cases of Bowen's disease. We found eight mutations in 20 cases, seven of which would produce alterations in the p53 protein product. Our results suggest that p53 mutation is an early event in malignant conversion, frequently preceding invasion in squamous cell neoplasia of the skin. The type and site of the observed mutations reflect known mutational hotspots and support the role of ultraviolet radiation in the pathogenesis of these tumors. PMID- 8496614 TI - Oligonucleotide typing reveals association of type I psoriasis with the HLA DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype. AB - Although the pathogenesis of psoriasis is still a matter of debate, there are several lines of evidence supporting the concept of this disease being immunologically mediated with T cells playing a crucial role. Because a considerable portion of the cellular infiltrate in psoriasis consists of activated T-helper cells, expression of HLA class II antigens might be of particular importance for the understanding of its pathogenesis. Therefore, we investigated the HLA type of patients with type I (early onset, positive family history) and type II (late onset, no family history) psoriasis by means of serology (n = 89) and genotyping using sequence-specific oligonucleotide probes (n = 64). Serologic analysis of class I documented the association of type I psoriasis with HLA-Cw6, -B13, and -B57, whereas type II psoriasis showed a weaker correlation with HLA-Cw2 and -B27. Genotyping using SSO for class II detected the elevation of the HLA-DRB1*0701/2 allele frequency from 13% in normal population to 36% in type I, but only to 15% in type II psoriatics. Moreover, positive correlations with type I psoriasis were detected for HLA-DQA1*0201 and HLA DQB1*0303. The HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype was found exclusively in type I psoriasis. This is the first report documenting the association of distinct HLA class II alleles with type I psoriasis as detected on the DNA level, an approach both more specific and more sensitive when compared to serology. PMID- 8496615 TI - Expression of cross-reactive idiotypes at the basement membrane zone in patients with bullous pemphigoid. AB - The purpose of the present study was to determine whether tissue-bound anti basement membrane zone (BMZ) autoantibodies in patients with bullous pemphigoid (BP) express a cross-reactive idiotype. We assayed 34 skin biopsies from 26 patients with BP and nine biopsies from control subjects, including normal subjects and patients with epidermolysis bullosa acquisita for the presence of a cross-reactive idiotype at the BMZ. Perilesional split-skin biopsies were assayed for the presence of immunoreactants, immunoglobulin G, and complement and for reactivity with a monoclonal anti-idiotypic antibody specific for a circulating anti-BMZ antibody, anti-Id 3-17. Anti-Id 3-17 bound in a linear band to the BMZ in 12 of 26 patients with BP (46%) and in 0 of 9 control subjects. In serial biopsy specimens, the presence or absence of cross-reactive idiotype at the BMZ in six patients was stable during the disease course. This cross-reactive idiotype has been previously identified in the serum of 36% of patients with BP; however, in this study, no correlation was noted between the presence of the cross-reactive idiotype in skin and serum of individual patients. Because cross reactive idiotypes occur as a consequence of restricted variable-region gene utilization, the demonstration of a cross-reactive idiotype at the BMZ previously identified in the serum of patients with BP supports the hypothesis that circulating and tissue-bound autoantibodies in this disease arise from a common genetic origin. PMID- 8496616 TI - Decreased type VI collagen gene expression in cultured Werner's syndrome fibroblasts. AB - Gene expression of collagens VI, I, and III in Werner's syndrome was studied by measuring messenger RNA (mRNA) and protein production levels in four fibroblast strains from patients with Werner's syndrome and comparing them with age-matched healthy subjects. Levels of type VI collagen mRNA were decreased in all Werner's syndrome fibroblast strains and the decreases were in parallel in all three chains (alpha 1, alpha 2, and alpha 3) of type VI collagen. A coordinate increase of the alpha 1(I) and alpha 1(III) collagen mRNA levels was observed in three of the four Werner's syndrome fibroblast strains. However, no qualitative abnormality of these mRNA transcripts in Werner's syndrome fibroblasts were found by Northern blot analysis. Changes in type VI and type I collagen mRNA correlated well with production levels of corresponding proteins, as determined by immunologic assays. These data suggest that there are changes in expression of multiple connective tissue constituents in Werner's syndrome fibroblasts. PMID- 8496617 TI - Gamma interferon potently induces tryptophanyl-tRNA synthetase expression in human keratinocytes. AB - Incubation of human keratinocytes with gamma interferon (gamma-IFN) induces the synthesis of a 53-kDa protein of unknown nature and function. We report the identification of this protein through amino acid microsequencing. The NH2 terminal amino acid sequence of the 53-kDa antigen demonstrated that this protein was tryptophanyl-tRNA synthetase (Frolova et al, Gene 109:291-296, 1991, Genbank accession number 61715). This result was validated by the sequencing of tryptic peptides. Identification of the 53-kDa gamma-IFN-induced protein was confirmed by immunoblotting with an antiserum directed against beef pancreas tryptophanyl-tRNA synthetase. Northern blot analysis using a synthetic oligonucleotidic 32P-labeled probe evidenced a 3.1-kb transcript in gamma-IFN-treated cells indicating that the gene was regulated at the pre-translational level. These data show that gamma IFN potently induces in keratinocytes the expression of an enzyme directly involved in protein biosynthesis. Elevated levels of tryptophanyl-tRNA synthetase in treated cultured keratinocytes might be involved in the cell-growth-inhibitory activity of gamma interferon. PMID- 8496618 TI - Biphasic effects of interleukin-1 alpha on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations. AB - Fibrotic reactions in the skin are frequently preceded by infiltration of inflammatory cells and subsequent migration of fibroblastic cells. Interleukin-1 is secreted by inflammatory cells and can regulate proliferation and protein synthesis of fibroblasts. Its role in fibroblast chemotaxis has not been elucidated in any detail. Using the well-established Boyden chamber assay for measurement of chemotaxis in vitro, we studied a wide range of recombinant human interleukin-1 alpha concentrations to assess intrinsic chemotactic activity of interleukin-1 alpha and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin-1 alpha dose required for enhancement of mRNA expression for collagenase. Although interleukin-1 alpha was not chemoattractive for fibroblasts, it specifically augmented migration toward fibroblast-conditioned medium and toward platelet-derived growth factor but not toward epidermal growth factor, fibronectin, or transforming-growth factor-beta. Interleukin-1 alpha did not measurably alter the expression of mRNA for the platelet-derived growth factor receptor or its platelet-derived growth factor-binding characteristics. Doses required to enhance fibroblast chemotaxis were distinctly lower than those required for stimulation of collagenase mRNA expression. PMID- 8496619 TI - Differential regulation of tyrosinase activity in skin of white and black individuals in vivo by topical retinoic acid. AB - Tyrosinase activity is a key determinant of melanin production in skin. Because retinoic acid regulates tyrosinase activity in melanoma cells, we analyzed modulation of pigmentation in vivo by retinoic acid. Black and white subjects were either not treated, or treated topically for 4 d under occlusion with vehicle, retinoic acid (0.1%), or the irritant sodium lauryl sulfate (2%). In untreated skin, tyrosinase activity and melanin content were significantly greater (2.3 times, and 3.2 times, respectively) in blacks versus whites. Four days of treatment with topical retinoic acid did not alter tyrosinase activity or melanin content in black skin. In contrast, retinoic acid treatment significantly induced (2.7 times, n = 8) tyrosinase activity, compared to vehicle treatment, in white skin. Melanin content, however, remained unchanged at 4 d. In separate experiments, tyrosinase activity in white subjects (n = 25) was increased 16% (p = 0.01) in sodium lauryl sulfate-treated skin, and 77% (p = 0.0005) in retinoic acid-treated skin, compared to vehicle-treated skin. The effect of retinoic acid on tyrosinase activity could be differentiated from non-specific irritation, because tyrosinase activity in retinoic acid-treated skin was significantly greater (52%, p = 0.004) than sodium lauryl sulfate-treated skin. Similar results were obtained with the dihydroxyphenylalanine reaction done on vehicle, sodium lauryl sulfate-, and retinoic acid-treated white skin. Northern analysis (n = 6) and semi-quantitative polymerase chain reaction (n = 6) demonstrated that retinoic acid treatment did not alter tyrosinase mRNA levels in white skin. Western analysis revealed that induction of tyrosinase activity by retinoic acid also was not associated with increased tyrosinase protein content (n = 9), indicating that regulation of tyrosinase activity by retinoic acid occurs through a post-translational mechanism. These data demonstrate that low tyrosinase activity in white skin in vivo is retinoic acid inducible and high tyrosinase activity in black skin in vivo is neither further induced nor reduced by retinoic acid. PMID- 8496620 TI - Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes. AB - Variations in human pigmentation among different racial groups are due to differences in the production and deposition of melanin in the skin. Although melanin synthesis is known to be controlled by the rate-limiting enzyme tyrosinase, the role of this enzyme as the principal determinant of skin pigmentation is unclear. Results from studies with human melanocyte cultures derived from different racial skin types reveal an excellent correlation between the melanin content of melanocyte cultures and the in situ activity of tyrosinase. Melanocytes derived from black skin have up to 10 times more tyrosinase activity and produce up to 10 times more melanin than melanocytes derived from white skin. However, the higher level of tyrosinase activity in melanocytes derived from black skin is not due to a greater abundance of tyrosinase. Results from immunotitration experiments and Western immunoblots reveal that the number of tyrosinase molecules present in white-skin melanocytes may equal the number found in highly pigmented black skin types. Moreover, approximately equivalent levels of tyrosinase mRNA are present in white and black skin cell strains. In contrast, melanocytes derived from red-haired neonates with low tyrosinase activity contain low numbers of tyrosinase molecules and low levels of tyrosinase mRNA. These results show that tyrosinase activity and melanin production in most light-skinned people is controlled primarily by a post translational regulation of pre-existing enzyme and not by regulating tyrosinase gene activity. In contrast, melanocytes from red-haired (type I) people have low levels of tyrosinase protein and mRNA, suggesting that transcriptional activity of the tyrosinase gene is suppressed. PMID- 8496621 TI - Cytolytic antibodies to melanocytes in vitiligo. AB - Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID- 8496622 TI - Coexistence and relationship of antikeratinocyte and antimelanocyte antibodies in patients with non-segmental-type vitiligo. AB - To test for autoantibodies in patients with vitiligo, skin biopsies from 16 patients with active vitiligo and 12 patients with stable vitiligo were examined by direct immunofluorescence. In periodate-lysine-paraformaldehyde-fixed biopsy specimens, the presence of IgG deposits in keratinocytes and the number of keratinocytes with focal IgG in active vitiligo were significantly greater than in stable vitiligo. To test whether the antibodies to normal human keratinocytes or melanocytes are present in vitiligo, we used an indirect immunofluorescent test and enzyme-linked immunosorbent assay to test the serum of 43 patients. With unfixed viable melanocytes, we found a granular pattern of IgG staining on the plasma membrane of melanocytes incubated with patients' sera but not in cells incubated with the control sera. With methanol-fixed melanocytes, however, we found a homogeneous pattern of IgG staining in the cytoplasm of melanocytes. With unfixed viable keratinocytes as targets, there was no deposit of IgG on the cells. A homogeneous pattern of IgG binding in the cytoplasm of methanol-fixed keratinocytes suggested the presence of antikeratinocyte autoantibodies to cytoplasmic keratinocyte components. The fluorescence staining for IgG binding was more prominent in active or extensive vitiligo. Vitiligo sera were cytotoxic for melanocytes but not for keratinocytes in vitro. Antimelanocytic antibodies may play a role in melanocytotoxicity, whereas antikeratinocyte antibodies may occur secondary to cellular damage. PMID- 8496623 TI - Inactivation of enzymes of the glutathione antioxidant system by treatment of cultured human keratinocytes with peroxides. AB - Either metal ions, H2O2, t-butyl hydroperoxide (tBHP), or cumene hydroperoxide (CHP) was added to the medium of cultured human keratinocytes, and the activities of key peroxide-metabolizing enzymes were examined in a sonicated cell supernatant from the treated cells. 200 microM Fe++ +200 microM Fe was without effect on any enzyme activity. 700 microM CHP or tBHP decreased glutathione (GSH) peroxidase activity by 90% after 5 h and by 100% at 20 h, even if the CHP or tBHP was removed from the media after 90 min. H2O2 at 700 microM caused a brief 17% decrease in activity, which was followed by complete recovery. GSH peroxidase was found to be rapidly inactivated in vitro by CHP, but the enzyme was also inactivated at 37 degrees C even in the absence of CHP. GSH prevented both types of inactivation. Consistent with this in vitro data, in vivo depletion of the GSH pool with buthionine sulfoximine led to lower levels of GSH peroxidase and increased sensitivity to peroxide-induced inactivation. Neither GSH reductase nor GSH S-transferase were inactivated by any treatment although CHP did cause a small increase in the activity of the latter, which was not due to induction. The activity of glucose-6-phosphate dehydrogenase was decreased 50% following treatment for 5 h with 700 microM CHP or tBHP, whereas H2O2 treatment caused a brief 15% decline, followed by recovery. The effects of peroxides were not altered by changing the concentration of Ca++ in the media. Catalase was unaffected by concentrations of peroxide up to 700 microM. Inhibition of catalase with aminotriazole slightly enhanced the toxicity of 700 microns H2O2. In summary, organic hydroperoxides at relatively low concentrations inactive key enzymes of the glutathione pathway, but hydrogen peroxide does not. PMID- 8496624 TI - Metabolism of freshly isolated human hair follicles capable of hair elongation: a glutaminolytic, aerobic glycolytic tissue. AB - The metabolism of the human hair follicle was investigated in vitro under conditions that maintained glycogen and adenosine triphosphate (ATP) content and the growth rate of the follicle at values observed in vivo. We have shown that only 10% of the total glucose utilized was oxidized to CO2 and 40% of this was oxidized via the pentose phosphate shunt. Although fatty acids and ketone bodies were oxidized by the hair follicle, they are poor energetic substitutes for glucose. Nor will fatty acids or ketone bodies sustain hair growth in vitro. Glutamine, however, was shown, both biochemically and by comparing growth rates, to be an important fuel with 23% of uptake being oxidized, generating a possible 2.16 +/- 0.32 nmoles ATP/follicle/h (mean +/- SEM) (glucose metabolism generates 4.54 +/- 0.61 nmoles ATP/follicle/h). Sixty-four percent of the glutamine taken up was calculated to be metabolized to lactate, showing that the hair follicle engages in both glycolysis and glutaminolysis. The glucose-fatty acid cycle appears to be unimportant in the hair follicle but our data indicates that a glucose-glutamine cycle does operate. PMID- 8496625 TI - Ganglioside GM3 inhibits the proliferation of cultured keratinocytes. AB - Ganglioside GM3 is the predominant ganglioside of keratinocyte membranes. It has been proposed in other cell types that GM3 may participate in the regulation of cell proliferation. To examine the role of GM3 in keratinocyte proliferation, purified GM3 was added to cultured keratinocytes from normal foreskin, from lesional skin of patients with psoriasis and ichthyosis, and to cutaneous squamous carcinoma cell lines. Supplemental GM3 inhibited the growth of all cultured keratinocytes in a dose-dependent manner at concentrations of 10-100 microM. Keratinocytes from patients with psoriasis and ichthyosis were most sensitive to the inhibitory effects of GM3, and confluent undifferentiated keratinocytes were least sensitive. No change in differentiation was noted after addition of GM3. GD3, 9-0-acetyl-GD3, and GD1b also inhibited keratinocyte proliferation. Gangliosides GM1 and GD1a and sialic acid had little effect. Addition of 50 microM 3H-GM3 to cultured keratinocytes resulted in 1.7 times the amount of cellular GM3. These data suggest that hematoside (GM3) and "b" pathway gangliosides (GD3, GD1b), generated by the preferential activation of sialyltransferase II versus N-acetylgalactosaminyltransferase, may be involved in control of keratinocyte growth but not of differentiation. PMID- 8496626 TI - New molecular targets and therapeutic strategies against cancer. PMID- 8496627 TI - Serum tumor markers in non-Hodgkin's lymphomas and chronic lymphocytic leukemia. AB - The levels of soluble interleukin-2 receptors (sIL-2R), beta-2 microglobulin (beta-2M), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured in the serum of 50 previously untreated patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) as well as in 25 age and sex-matched normal controls. Compared to normal controls, mean serum levels of sIL-2R and beta-2M were significantly increased in both NHL and CLL (p < 0.001) while the increase in ESR and CRP was less marked (p < 0.01 and p < 0.05, respectively). Comparison of these tumor markers with histologic grading showed statistically significant differences only for CRP between low, intermediate and high-grade lymphomas (p < 0.001 and p < 0.05). More advanced stages exhibited higher mean values of all serum markers than early stages (p < 0.001 for sIL-2R, beta-2M and ESR and p < 0.05 for CRP). An association with the presence of b symptoms was observed only for sIL-2R (p < 0.05). In addition, sIL-2R as well as beta-2M were able to predict time to progression in patients with diffuse large cell lymphomas. We conclude that of the four tumor markers tested sIL-2R and beta 2M more frequently showed increased serum levels and were associated with clinical stage and/or presence of b-symptoms. Both sIL-2R and beta-2M were also found to have prognostic significance for survival. PMID- 8496628 TI - CAM26 cytosol levels seem to be correlated with pS2 expression in breast cancer. PMID- 8496629 TI - A new approach to tumour marker assessment by perioperative determination in breast and colorectal cancer. AB - Preoperative serum tumour markers are currently classified as positive or negative according to a predetermined cut-off point. In the present study we examined the dynamic variation of marker levels after radical surgery of breast and colorectal cancer. CEA and CA15.3 were measured in 93 patients with breast cancer, CEA and CA19.9 in 97 patients with colorectal carcinoma before and 30 days after radical surgery. Any variation higher than 3-fold the analytical coefficient of variation of the assay was considered significant. In patients with negative preoperative marker levels a significant decrease was noted after surgery in 15.6% of cases for CEA and 27.8% for CA15.3 in breast cancer and in 46.8% for CEA and 25.7% for CA19.9 in colorectal cancer. Using both cut-off-based and dynamic criteria, we found an overall positivity rate of 19.6% for CEA and 33.3% for CA15.3 in breast cancer; 60.0% for CEA and 37.1% for CA19.9 in colorectal cancer. From the present findings we conclude that the dynamic study of perioperative variations of tumour markers is a sensitive method additional to cut-off-based criteria for the assessment of the phenotypic expression of the marker by the tumour. PMID- 8496630 TI - [67th annual meeting of the Japanese Association for Infectious Diseases. Tokyo, Japan. April 15-16, 1993. Abstracts]. PMID- 8496631 TI - [Interleukin-6 production in endometriosis]. AB - The purpose of this study was to assess whether endometriotic implants of endometriosis could produce Interleukin (IL)-6. IL-6 was measured by means of an enzyme-linked immunosorbent assay (ELISA) in 21 patients with endometriosis of stage IV according to R-AFS classification of endometriosis. The tissues obtained from endometriotic implants were incubated for 24 hours and all their supernatants (n = 8) were positive for IL-6 and the mean level of IL-6 was approximately 30pg/ml per 1mg tissue dry weight. The level of IL-6 in the supernatant did not correlate with the serum estradiol level or with positivity against autoimmune antibodies in patients with endometriosis before surgery. The cultured stromal cells obtained from endometriotic implants were immunohistochemically positive for rabbit antihuman IL-6 polyclonal antibodies. IL-1 alpha (0.5ng/ml) and lipopolysaccharide (LPS) (10 micrograms/ml) caused a 50% and a 130% increase respectively, in IL-6 production in untreated cells (p < 0.01) of 24-hour culture (n = 3). On the other hand, estradiol, progesterone and danazol apparently had no effect on IL-6 production. The serum IL-6 levels of patients with myoma uteri (n = 10) were significantly (p < 0.05) enhanced after surgery, while those of patients with endometriosis (n = 14) declined after surgery. The anti IL-6 antibodies between 10ng/ml and 100ng/ml inhibited cell growth 20% (p < 0.05), while IL-1 alpha (0.5ng/ml) inhibited cell growth 50% (p < 0.01) in a 5 day cell culture (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496632 TI - [Non-reactive pattern diagnosed by ultrasonic Doppler fetal actocardiogram and outcome of the fetuses with non-reactive pattern]. AB - The accuracy of diagnosis by means of ultrasonic Doppler fetal actocardiogram in non-stress test (NST) was examined in 100 fetuses at 32 to 42 weeks of gestation. Fourteen fetuses were diagnosed as non-reactive by conventional NST which monitored fetal heart rate, but only 4 of the 14 fetuses were found to be "non reactive" when the fetal actocardiogram was used. Thus the false positive rate obtained with conventional NST in judging the non-reactive pattern was 71.4% (10/14). We next examined the outcome for 25 fetuses (including 20 IUGR cases) with a "non-reactive pattern" who were diagnosed by fetal actocardiogram. Fetal distress occurred in 19 of these fetuses (76.0%), and mostly developed within 5 days after the diagnosis of "non-reactive pattern". The outcome for 20 IUGR fetuses with a "non-reactive pattern" was compared with that for fetuses with a "reactive pattern". IUGR fetuses which were "non-reactive" had a significantly higher fetal distress morbidity rate, and higher cesarean section rate. The sensitivity and specificity of the prediction of the development of fetal distress in IUGR fetuses with a "non-reactive pattern" were 81.0% and 84.2%, respectively. The present results strongly suggest the need to use the ultrasonic Doppler fetal actocardiogram at the time of NST after 32 weeks of gestation. PMID- 8496633 TI - [Antinuclear antibody measurement as a screening test for sterile and infertile women with immunological abnormality]. AB - The efficacy of examining antinuclear antibody (ANA) was investigated as a screening test detecting subclinical immune disorders in infertility and sterility. ANA was measured in 116 unexplained infertile or sterile patients. The ANA positive rate was 43.5% in group A (habitual abortion, n = 23), 38.1% in group B (consecutive miscarriages, n = 21), 30.0% in group C (one miscarriage, n = 10), 16.7% in group D (one or more deliveries n = 12) 22.0% in group E (primary sterility, n = 50), and 22.4% in the control group (n = 54). The positive rate for all the infertile patients (group A+B) was 40.9% and significantly higher than that in for the control group (p < 0.05). Ten patients with positive ANA had 12 deliveries and 20 patients with negative ANA had 23 deliveries. The frequency of preeclampsia in the patients with positive ANA was higher than in those with negative ANA (41.7% versus 4.3%, p < 0.05). A higher incidence of premature deliveries was recognized in the patients with positive ANA than in those with negative ANA (41.7% versus 8.7%, p < 0.1). Average birth weight (> 35 week) for patients with and without positive ANA was 2,976g (n = 8) and 3,122g (n = 19) respectively. The former tends to be smaller than the latter (p < 0.1). PMID- 8496634 TI - [Chemotherapy of ovarian cancer with a combination of low-dose consecutive CDDP and cyclophosphamide]. AB - Sixty-six patients with ovarian cancer were treated with low-dose consecutive CP (LDC-CP) consisting of cyclophosphamide (CPM: 500 mg/m2, day 1) and CDDP (10 mg/m2, days 1-7). Two-9 (median: 4) courses of LDC-CP were given following reduction surgery (42 cases) or preceding primary debulking (24 cases). Among 66 cases, 12 with stage Ic were not evaluable (NE). The response rate (CR + PR/evaluable) for stages II-IV was 57.4% (12 + 19/54). Histologically, serous and endometrioid type showed a significantly (p < 0.001) higher response rate (77.5% among 40 evaluable) compared to the other histologic type (0% among 14). Toxicities including nausea/vomiting and renal impairment were markedly mild or almost absent despite the lack of any particular care. Grade 3 leucopenia and thrombocytopenia were observed only in 4.2%, and 2.5% of total 284 courses, respectively. Mean survival time by stage was 1,309 days for stage I, 809 days for stage II, 1,180 days for stage III, and 691 days for stage IV, with a significant difference among stages (p = 0.0452). In stages III and IV disease, significant prognostic factors included 1) response to chemotherapy, 2) no. of LDC-CP courses, 3) histologic subtype, 4) performance status, and 5) tumor size. Thus, LDC-CP is considered to be a useful chemotherapeutic regimen for serous and endometrioid type ovarian cancer. PMID- 8496635 TI - [Blood flow pattern and tumor vascular change following intraperitoneal administration of CDDP in VX2 ovarian tumor]. AB - Following intraperitoneal(IP) administration of cis diamminedichloroplatinum(CDDP), a dynamic study was conducted on rabbits in Angiotensin II(ATII) induced hypertension to investigate hemodynamic changes in VX2 ovarian tumors. VX2 tumors for transplantation were prepared in Japanese white female rabbits. 15mg/kg of CDDP in 30ml/kg 0.9% NaCl solution was IP administration to the rabbits. The tissue platinum(Pt) concentration was measured and tumor vascular model prepared. The rabbits also received IP combined with 1.2g/kg intravenous administration of sodium thiosulfate(STS), and a hemodynamic study was run on rabbits with ATII induced hypertension two weeks after administration. IP administration resulted in tissue Pt levels as high as 18.50 +/- 8.05 micrograms/g in the VX2 ovarian tumors, with a tiny non-enhanced area appearing in the rim enhancement, consistent with necrotic changes. The tumor time-density curve following IP was characterized by a markedly delayed washout, with many hypovascular portions noted in the vascular model and a clear decrease in tumor vessels measuring 30 microns or less. in contrast, the peak value increased in the time-density curve and there was washout in the excretory phase following ATII induced hypertension. In view of the results, we suggest that a microcirculatory disorder resulting from IP administration could be improved under ATII induced hypertension. PMID- 8496636 TI - [Allelic losses of tumor suppressor gene on chromosome 17 in ovarian cancer]. AB - Twenty-one human ovarian epithelial carcinomas (13 serous, 3 mucinous, 2 endometrioid and 3 clear cell type) were examined for allelic losses of p53 tumor suppressor gene, pYNZ22 or pTHH59 on chromosome 17. High-molecular-weight DNA was extracted from ovarian tumor tissues and normal ones obtained from the same patients, and was subjected to Southern blot analysis. The filters were hybridized with p53 cDNA probe or two VNTR probes on chromosome 17(pYNZ22, pTHH59). By comparing the hybridized band pattern of the normal tissue with that of the tumor, loss of heterozygosity (LOH) was detected. Frequent LOHs were detected in 5 of 14 informative cases (36%) on p53 and in 9 of 20(45%) on pYNZ22, but LOH on pTHH59 was observed less frequently than those of p53 and pYNZ22 (one of 7 cases: 14%). These results suggest that allelic loss of p53 may play an important role in the development and/or progression of ovarian carcinomas. PMID- 8496637 TI - [Lipoleiomyoma of the uterus: report of a case]. PMID- 8496638 TI - [A case report of uterine lipoleiomyoma]. PMID- 8496639 TI - A review of patients attending a preliminary cochlear implant assessment clinic. AB - The Cochlear Implant Programme at Manchester Royal Infirmary was established in 1988 and so far (January, 1992) 38 patients have been implanted with the Nucleus 22 channel intracochlear device and one with the Ineraid device. All patients who are referred for consideration for an implant are initially seen at a preliminary cochlear implant assessment clinic conducted by an ENT surgeon. One hundred and seventy three patients attended the initial outpatient screening clinic between 1987 and January 1992. Of these 112 patients (67.6 per cent) went on for further investigation regarding suitability for implantation. This paper details the aetiology and severity of deafness in these patients and explains how suitability for admission to the next stage of assessment was decided. PMID- 8496640 TI - The mini-grommet and tympanosclerosis: results at two years. AB - One hundred and sixteen children with otitis media with effusion (OME) underwent surgery with grommet insertion. A conventional Shah grommet was used in one ear, and a Mini-Shah grommet in the other. Final review of the subjects two years after surgery revealed a significantly lesser degree of tympanosclerosis in the ear into which the Mini-Shah grommet had been inserted. This benefit might have resulted from the lesser mass of the mini-tube or its shorter duration in situ. PMID- 8496641 TI - Transcranial translabyrinthine approach to vestibular schwannomas. AB - Surgeons who utilize the suboccipital approach for the removal of large vestibular schwannomas, can perform a planned labyrinthectomy from within the intracranial cavity via the suboccipital exposure. This transcranial translabyrinthine approach provides one of the major advantages of the conventional transmastoid translabyrinthine approach, namely, unambiguous identification of the facial nerve as it exits the internal auditory canal, without the need for complete mastoidectomy and labyrinthectomy. The labyrinthectomy is best performed prior to the complete exposure of the internal auditory canal. The approach requires the surgeon to identify the endolymphatic sac intracranially, then drill the temporal bone and follow the vestibular aqueduct to the utricle. The lateral and superior semicircular canal ampullae, the superior vestibular nerve, Bill's bar, and the facial nerve at the lateral end of the internal auditory canal can then be identified. After testing on multiple cadaver temporal bones, this approach was used in patients with large tumours that extended far laterally in the internal auditory canal. The steps in the technique are described in detail. PMID- 8496642 TI - Brachytherapy for recurrent nasopharyngeal and naso-ethmoidal tumours. AB - Recurrent or persistent carcinoma of the nasopharynx or naso-ethmoid region occurs even after combined surgery and radical external irradiation. The confined bony access and proximity of vital structures may compromise resection margins. Brachytherapy using implantable radioactive gold or iodine seeds is a useful adjunct to the skull base surgeon in eliminating residual microscopic disease. We report nine cases with recurrent or persistent disease of the nasopharynx or naso ethmoid regions treated with brachytherapy with encouraging results. PMID- 8496643 TI - A guided approach to surgery for aspiration: two case reports. AB - Aspiration frequently occurs in patients with a competent glottis. Analysis using a modified barium swallow (MBS) can reveal an extraglottic mechanism of aspiration in these patients. The MBS examination guided the design of two surgical procedures in patients with severe aspiration. The surgery corrected the underlying extraglottic cause of aspiration while preserving glottic function. In one case the epiglottoplasty controlled aspiration due to spillage over the epiglottis into the airway. In the other case translaryngeal resection of the cricoid lamina combined with cricopharyngeal myotomy controlled aspiration of residue in the hypopharynx. After surgery, both patients had their gastrostomy and cuffed tracheostomy tubes removed and were discharged home on a normal oral diet. Detailed analysis of deglutition by a modified barium swallow can provide a scientific basis to guide the surgical management of patients with severe dysphagia. PMID- 8496644 TI - Tularemia: a differential diagnosis in oto-rhino-laryngology. AB - Tularemia can present as an oto-rhino-laryngological disease. The clinical and radiological (CT) manifestations, diagnosis and treatment are discussed based on a case report where a patient with tonsillitis and enlarged cervical lymph nodes was admitted to the department of oto-rhino-laryngology of a hospital in Northern Norway. Francisella tularensis was isolated from the blood and there was a high titre of agglutinating serum antibodies to F. tularensis. The patient's contaminated drinking water well is the suspect source of infection. PMID- 8496645 TI - Radiotherapy and complications of laryngectomy. AB - In an effort to establish factors responsible for our post laryngectomy fistulae we reviewed 357 patients who underwent total laryngectomy between 1965 and 1990, for laryngeal carcinoma. Pharyngocutaneous fistulae occurred in 84 cases (23 per cent). There was no difference between the fistula group and the non-fistula group with regard to age, sex, general condition, or tumour differentiation. The only significant, positive association was with previous radical radiotherapy (10 fistulae out of 167 primary laryngectomies (4 per cent) versus 74 fistulae out of 190 salvage laryngectomies (39 per cent)). The median time to occurrence of a fistula was day seven in both groups. However, in the non-radiotherapy group the median duration of the fistula was 28 days; the majority healing spontaneously, with only one patient requiring surgical closure. There were no 'hospital' deaths. In the radiotherapy group the median duration of fistulae was 112 days with 30 patients requiring a total of 66 procedures to achieve closure of the fistula. There were six 'hospital' deaths in this group. We conclude that previous radical radiotherapy strongly predisposes towards the occurrence of a post-laryngectomy fistula. Fistulae in this group tend to be longer lasting and are more likely to require surgical repair. PMID- 8496646 TI - Head and neck manifestations during HIV infection. AB - The ENT manifestations of HIV infection are well known and the findings in AIDS patients have been described, nevertheless there are no reports of the frequency of head and neck involvement during the various stages of the disease. From 1987 to 1991, 210 HIV positive patients had ENT evaluation without symptoms-related selection. The majority of them were men and intravenous drug users. The frequency of enlarged neck nodes, neck mass, nasopharyngeal lymphatic tissue hypertrophy, extranodal localization of non-Hodgkin's lymphomas, Kaposi's sarcoma, oral hairy leukoplakia, candidiasis and other less common findings is reported, in relation to the stage of the disease. Overall 84 per cent of the observed patients had head and neck manifestations. An ENT evaluation in every HIV infected patient is suggested. PMID- 8496647 TI - Beware bleeding from the ear. AB - We present the case of a 55-year-old man who presented with intermittent, profuse bleeding from the ear five years following radiotherapy for a nasopharyngeal carcinoma. He had developed osteoradionecrosis of the temporal bone, and the bleeding was shown to originate from an aneurysm of the internal carotid artery within his temporal bone. This has not previously been reported as a complication of radiotherapy for nasopharyngeal cancer. PMID- 8496648 TI - Respiratory obstruction associated with the use of the Brighton epistaxis balloon. AB - A case is reported where posterior displacement of a Brighton balloon catheter (Eschmann) is thought to have led to inhalation of clot from the nasal cavity with subsequent respiratory obstruction. Precautions in using this type of epistaxis balloon are discussed. PMID- 8496649 TI - Posterior epistaxis and the undeflatable Foley's urinary catheter balloon. AB - A rare complication relating to the use of a Foley catheter in the control of posterior epistaxis is described. The balloon failed to deflate after the catheter had been in place for 32 hours and per-oral removal was required. PMID- 8496650 TI - Renal derived epistaxis. AB - A solitary metastasis to the nose from a renal cell carcinoma is extremely rare. One such case is presented and the argument for aggressive therapy to these lesions is reviewed. PMID- 8496651 TI - Malignant schwannoma arising in a paranasal sinus. AB - A case of malignant schwannoma arising in a paranasal sinus is reported. In this case, histological hallmarks were lost because of the poorly differentiated nature of the tumour. Immunohistological techniques were applied to the diagnosis, confirming the neural origin of this tumour. Malignant schwannoma is a relatively rare disease in the nasal cavity and paranasal sinuses. For the treatment of this tumour, wide resection is recommended. In this patient, radical resection of the maxilla with orbital and ethmoid exenteration was performed. The patient recovered uneventfully with no evidence of disease three years after surgery. PMID- 8496652 TI - Nasopharyngeal carcinoma in an HIV-positive patient causing severe morbidity and early death. AB - A nasopharyngeal carcinoma was the first event in an otherwise symptom free HIV person. No reports of simultaneous nasopharyngeal carcinoma and HIV infection are known to us. A 46-year-homosexual man was admitted to the ENT department with a three week history of pain in the throat referred to the left ear. He was found to have an irregular tumour in the nasopharynx with a lymph node metastasis to the left side of the neck. The poor response to radiotherapy and the very aggressive progress after treatment raised suspicion of a co-existing disease process. The risk of sexually transmitted HIV was confirmed post mortem and could explain the rapid progression of the tumour. No anti-HIV treatment was given concurrently with radiotherapy. PMID- 8496653 TI - Munchausen syndrome by proxy: otolaryngologists beware! AB - Munchausen syndrome by proxy (MSBP) is a rare condition in which a parent or guardian fabricates an illness in a child either by inducing physical signs or prevaricating. A case presenting as recurrent episodes of infant apnoea is reported. A high index of suspicion is required for the diagnosis and, therefore, the otolaryngologist must be familiar with the condition if the life of the infant is to be protected and potentially harmful unnecessary investigations are to be avoided. PMID- 8496654 TI - Bay-leaf: an unusual oesophageal foreign body. AB - Bay-leaf as a foreign body causing oesophageal obstruction has rarely been reported. We present two such cases, and review their management. PMID- 8496655 TI - Ectopic cervical hamartomatous thymoma showing extensive myoid differentiation. AB - Ectopic 'hamartomatous' thymoma is a rare benign neoplasm. These tumours are found in the neck and are thought to be part of a spectrum of ectopic cervical thymic neoplasia. The clinical and histological features are discussed and the literature is reviewed. An attempt is made to explain in embryological terms why such lesions appear to occur more commonly on the left side. PMID- 8496656 TI - Radiological diagnosis of spheno-choanal polyp. AB - Spheno-choanal polyp is a rare entity which presents in a similar manner to the more common antro-choanal polyp. There is often difficulty clinically in differentiating the two conditions, although their radiological characteristics are distinct. A case of spheno-choanal polyp is presented and the plain radiograph and the CT findings reviewed. PMID- 8496658 TI - Bone anchored hearing aids and prostheses. PMID- 8496657 TI - Subtle diagnostic markers of orbital floor blow-out fracture on coronal CT scan. AB - The sagittal plane, computerized tomography (CT) scan has been proposed as the most important radiological view in the diagnosis of orbital floor blow-out fractures. This view however is impractical and unnecessary. Direct, coronal plane CT scan with careful attention paid to the shape of the inferior rectus muscle and antral roof will successfully diagnose this traumatic condition, as in our reported case in which no other radiological abnormalities were present. PMID- 8496659 TI - Familial hypobetalipoproteinemia. PMID- 8496660 TI - Lipid transfer particle in the hemolymph of the American cockroach: evidence for its capacity to transfer hydrocarbons between lipophorin particles. AB - A lipid transfer particle (LTP) was isolated and purified from the hemolymph of the adult male American cockroach, Periplaneta americana, essentially according to the method previously developed for the purification of LTP from locust hemolymph. Fast protein liquid chromatography (FPLC) on a Mono Q column was used as the additional step to obtain pure LTP. The electron micrograph of purified cockroach LTP exhibited an unusual and asymmetric shape essentially similar to that reported for Manduca sexta LTP (Ryan et al. 1990. J. Lipid Res. 31:871-879). The cockroach LTP was also found to be basically similar to that of M. sexta and locust in terms of subunit structure and lipid composition, although there were significant differences particularly in the contents of hydrocarbons and diacylglycerol. A simple method for assaying LTP activity was developed, based on the finding that cockroach LTP can catalyze the transfer of labeled hydrocarbons (or diacylglycerol) from labeled high density lipophorin (HDLp) bound with a transfer membrane (Immoblion) to unlabeled HDLp dissolved in saline. This finding reveals that cockroach LTP has the capacity to transfer and/or exchange lipids between lipophorin particles with the same density. It was also demonstrated that cockroach LTP has the capacity to catalyze the transfer and/or exchange of hydrocarbons, in addition to diacylglycerol, between cockroach HDLp and locust low density lipophorin (LDLp). PMID- 8496661 TI - Taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen-24-oic acid (tauro-delta 22-beta-muricholate): the major bile acid in the serum of female rats treated with alpha-naphthylisothiocyanate and its secretion by liver slices. AB - The taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen-24-oic acid (tauro-delta 22-beta-muricholate) has been identified in the serum of female rats treated with alpha-naphthylisothiocyanate. Using a high performance liquid chromatographic/enzymatic method for measurement of bile acids, tauro-delta 22 beta-muricholate was the predominant bile acid in the serum of female Fischer 344 rats treated for 3 days with alpha-naphthylisothiocyanate. Other significant changes in concentrations of serum bile acids included increases in tauro-alpha muricholate, tauro-beta-muricholate, taurocholate, taurochenodeoxycholate, and several unknown bile acids. The formation of tauro-delta 22-beta-muricholate was examined in vitro using liver slices from control rats and rats treated with alpha-naphthylisothiocyanate. Slices were incubated for 7 h in William's E medium containing no bile acids or 25 mumol/l of one of the following: beta-muricholate, tauro-beta-muricholate, or cholate. Tauro-delta 22-beta-muricholate was secreted by slices from control and treated rats and the rate was increased significantly by the addition of beta-muricholate (2.9-5.6-fold) but not tauro-beta-muricholate or cholate to the medium. Tauro-delta-beta-muricholate was formed by liver slices from endogenous precursors and from exogenous beta-muricholate. Pretreatment of rats with alpha-naphthylisothiocyanate did not alter total secretion rates but those of some important individual bile acids were affected. Because of the increased secretion of tauro-delta-beta-muricholate by liver slices with the addition of beta-muricholate to the medium, the liver may be the primary site of formation for this unsaturated bile acid. PMID- 8496662 TI - Interaction between sphingosine and cholesteryl sulfate in epidermal lipids. AB - Free sphingosine, a material with multiple and potent biological activities, is known to occur in high concentration in mammalian epidermis. In the present study, thin-layer chromatography showed that in lipid extracts of human and pig stratum corneum, sphingosine forms a relatively stable compound with endogenous cholesteryl sulfate. NMR spectrometry of sphingosine and its hydrochloride, sulfate, and mixtures with cholesteryl or dodecyl sulfate showed that interaction with the organic sulfates constituted simple salt formation. Under neutral or weakly acidic conditions, such salts were only slightly dissociated and migrated on thin-layer chromatograms as discrete compounds. Thin-layer chromatography revealed undissociated salt formation between several long-chain bases and organic sulfates, and showed that their interaction is stoichiometric. However, undissociated salts were not formed between long-chain bases and fatty acids or phosphatidic acid. Undissociated salt formation may therefore be specific for organic bases and sulfates. It was concluded that the free sphingosine in the stratum corneum may be present as its cholesteryl sulfate salt and in this form be unavailable for permeation into the viable epidermal cells. PMID- 8496663 TI - Role of HDL1 in cholesteryl ester uptake in rats. AB - It has been suggested that apoE may play a central role in reverse cholesterol transport in rats. By this hypothesis, cholesteryl esters (CE) accumulate in high density lipoprotein (HDL) particles, which acquire apoE at the expense of apoA-I, and the apoE targets them for rapid hepatic uptake. However, the pathway has not been directly assessed in vivo. We directly traced the metabolism of HDL1 cholesteryl esters in rats. To do this, rat HDL1 was labeled in its apoE and CE moieties, and HDL2 free of apoE was labeled in its apoA-I and CE moieties; 14C- or 3H-labeled cholesteryl-oleyl ether traced the CE moieties and the 125I- or 131I-labeled N-methyltyramine cellobiose (NMTC) ligand traced the apolipoprotein moieties. The labeled HDLs were injected, plasma decays were followed, and tissues were examined after 24 h. ApoE tracer decayed from plasma 2.4-times faster than HDL1 CE and 1.8-times faster than HDL2 CE. HDL1 CE decayed significantly more slowly than HDL2 CE (0.75-times). As expected, hepatic uptake of HDL2 CE was mostly by selective (indirect) uptake. However, hepatic uptake of HDL1 CE was at a fractional rate significantly lower than that of HDL2 CE (0.69 times), even though the uptake of apoE was much higher. The plasma decay of HDL1 apoE evidently reflects in large part the uptake of apoE after transfer to other fractions, and it over-estimates the clearance of HDL1 CE. Selective uptake plays the major role in hepatic HDL CE uptake in rats. PMID- 8496664 TI - Cholesterol and 27-hydroxycholesterol 7 alpha-hydroxylation: evidence for two different enzymes. AB - The use of 2-hydroxypropyl-beta-cyclodextrin as a vehicle for solubilizing cholesterol and 27-hydroxycholesterol has led to a study of their rates of 7 alpha-hydroxylation in microsomal preparations from hamster liver and HepG2 cells. Addition of the vehicle alone to the cholesterol 7 alpha-hydroxylase assay always caused a several-fold increase in activity. Preloading the vehicle with cholesterol further augmented the rate of 7 alpha-hydroxycholesterol formation. Preloading the vehicle with 27-hydroxycholesterol or 27-hydroxycholestanol (molar ratio 1/1.2) minimally decreased cholesterol 7 alpha-hydroxylase activity (-12%), compared with preloading with cholestanol (-50%), a known competitive inhibitor of the enzyme. Microsomes from hamster liver yielded rates of 7 alpha,27 dihydroxcholesterol formation of 1.5 to 3.0 nmol/min per mg protein, compared with 0.3 nmol/min per mg protein for 7 alpha-hydroxycholesterol. Although cholesterol and cholestanol had minimal effects on the rate of 7 alpha hydroxylation of 27-hydroxycholesterol, addition of an approximately equimolar amount of 27-hydroxycholestanol inhibited the rate of formation by 65%. Attempts to separate and identify the two C-27 sterol 7 alpha-hydroxylases chromatographically led to the finding that Emulgen 913 selectively inactivates 7 alpha-hydroxylation of 27-hydroxycholesterol. These results indicate that the metabolic pathway for bile acid synthesis from 27-hydroxycholesterol is not governed by cholesterol 7 alpha-hydroxylase. PMID- 8496665 TI - Less polar glycolipids in Alaskan pollack brain: isolation and characterization of acyl galactosyl diacylglycerol, acyl galactosyl ceramide, and acyl glucosyl ceramide. AB - We recently reported that glycolipid compositions of gadoid fish nerve tissues are unique in the abundance of 1) galactosyl diacylglycerol and its sulfate ester; 2) glucosyl ceramide; and 3) fatty acid ester of cerebroside (J. Lipid Res. 1992. 33: 1351-1359). The present paper reports the characterization of less polar glycolipids isolated from Alaskan pollack brain. Of twelve glycolipids purified by column chromatography, four were of the galactosyl diacylglycerol type. Chemical analysis, infrared spectrometry, and a permethylation study followed by gas chromatography-mass spectrometry revealed that they were 1,2-di-O acyl-3-beta (6-O-acyl-D-galactopyranosyl)-sn-glycerol and 1,2-di-O-acyl-3-beta(2' O-acyl-D-galactopyranosyl)-sn-glycerol, and mixtures of these two isomers, with slightly different fatty acid compositions, respectively. The other eight less polar glycolipids were pure forms or mixtures of isomeric forms of cerebroside fatty acid esters in which the substituted position of the acyl group on the hexose moiety varied. The permethylation study revealed that they were 6-O-acyl beta-D-galactopyranosyl, 6-O-acyl-beta-D-glucopyranosyl, 2-O-acyl-galactosyl, 2-O acyl-glucosyl, 3- or 4-O-acyl-galactosyl, and 3-O-acyl-glucosyl ceramides, the 6 O- and 2-O-acyl isomers being predominant. This is the first report of the natural occurrence of 1) acyl galactosyl diacylglycerol in animal tissues and 2) acyl glucosyl ceramide in nerve tissues. PMID- 8496666 TI - Detection of hormone-sensitive lipase in various tissues. II. Regulation in the rat testis by human chorionic gonadotropin. AB - Hormone-sensitive lipase (HSL) is an intracellular neutral lipase found in a variety of tissues, primarily in adipose and steroidogenic tissues, that hydrolyzes triglycerides and cholesteryl esters. In the rat testis steady-state levels of HSL mRNA increase dramatically during sexual maturation. In addition, HSL-like immunoreactive proteins of 84, -89, and -102 kD have been observed in sexually immature rats with additional -113 and -127 kD immunoreactive proteins expressed in mature animals. In the present studies the ability of human chorionic gonadotropin (hCG) to regulate the expression of HSL and HSL-like immunoreactive proteins in rat testes has been examined. Treatment of sexually immature rats with daily injections of hCG caused a gradual increase in HSL activity that reached an 80% rise (P < 0.01) after 5 days. This was paralleled by a 3-fold increase (P < 0.01) in the 84 kD protein representing the active HSL enzyme. The -89 kD immunoreactive protein was also increased -5-fold (P < 0.01) in parallel to the 84 kD protein and HSL activity. The -102 kD immunoreactive protein was increased by hCG treatment (P < 0.01); however, its expression did not follow changes in HSL activity or in the 84 and -89 kD immunoreactive proteins, peaking within 12 h and declining thereafter. The -113 and -127 kD immunoreactive proteins did not appear during the 5 days of hCG treatment. Steady state levels of HSL mRNA increased 60-100% (P < 0.02) in parallel to the changes in HSL activity and in the 84 and -89 kD immunoreactive proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496667 TI - Intestinal expression of the human apoA-I gene in transgenic mice is controlled by a DNA region 3' to the gene in the promoter of the adjacent convergently transcribed apoC-III gene. AB - The apoA-I gene in humans is principally expressed in liver and small intestine. Using transgenic mice, we previously showed that 256 bp of 5' flanking DNA was sufficient for liver expression, but as much as 5.5 kb of 5' and 4.0 kb of 3' DNA did not allow intestinal expression of the human apoA-I transgene. In the current study, a 10.5 kb DNA construction containing the apoA-I and the adjacent convergently transcribed apoC-III genes, which extends from 300 bp 5' to the apoA I gene to 2.5 kb 5' to the apoC-III gene, produced high levels of apoA-I intestinal expression. A similar DNA construction ending 1.4 kb 5' to the apoC III gene also allowed apoA-I intestinal expression. The DNA region from 0.2 to 1.4 kb 5' to the apoC-III gene was then cloned 1.7 kb 3' to the apoA-I gene in both orientations in the absence of apoC-III gene sequences. Intestinal apoA-I expression was also achieved with both of these constructions. In summary, these in vivo experiments suggest that the intestinal control region for the apoA-I gene is distinct from the liver control region, resides 3' to the gene in the promoter of the adjacent apoC-III gene, and has some properties of a tissue specific enhancer. PMID- 8496668 TI - Metabolism of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid by kidney and liver peroxisomes. AB - 12(S)-Hydroperoxy-5,8,10,14-eicosatetraenoic acid (12(S)-HPETE) is one of the main products formed from arachidonic acid by animal lipoxygenases. It is usually reduced to the corresponding hydroxy acid, 12(S)-hydroxy-5,8,10,14 eicosatetraenoic acid (12(S)-HETE) or it can serve as an intermediate in the biosynthesis of hepoxilins. The functions of 12(S)-HETE are incompletely understood but it has been proposed that it plays a role in the metastatic process of certain cancer cells, including Lewis lung carcinoma cells. 12(S)-HETE is metabolically degraded by beta- or omega-oxidation. Indirect evidence has suggested involvement of peroxisomes in the beta-oxidative degradation. The purpose of the present investigation was to study 12(S)-HETE metabolism by peroxisomes isolated from rat liver or kidney by sucrose density gradient centrifugation. The purity of subcellular fractions was determined by marker enzyme analyses and electron microscopy. 12(S)-HETE was quantitatively converted by liver or kidney peroxisomes into a single, diethyl ether-extractable metabolite. This was identified by gas-liquid chromatography-mass spectrometry as 8-hydroxyhexadecatrienoic acid. Lewis lung carcinoma cells also metabolized 12(S) HETE to 8-hydroxyhexadecatrienoic acid. PMID- 8496669 TI - Release of small amounts of free fatty acids from human adipocytes as determined by chemiluminescence. AB - A semiautomatic luminometric method for determination of small amounts of free fatty acids (FFA) released from human adipocytes in vitro is described. Bovine serum albumin (BSA) is used as acceptor of free fatty acids in the incubation medium of isolated fat cells. The assay involves pretreatment with the detergent sodium dodecyl sulfate (SDS) to liberate the free fatty acids from the bovine serum albumin before activation by acyl-CoA synthetase (ACS) (EC 6.2.1.3). This is followed by oxidation of the resulting thioesters by acyl-CoA oxidase (ACO). The H2O2 formed is subsequently measured in a horseradish peroxidase (HRP) (EC 1.11.1.7)-catalyzed luminol reaction. The assay is linear in the interval of 0.01 1 nmol in the cuvette corresponding to 2-200 microM in the sample, and 25 samples are automatically assayed in the luminometer within 75 min. FFA release could easily be studied in a small incubation volume (200 microliters) of very diluted (10(4) cells/ml) human adipocyte suspensions. Samples (25 microliters) containing 0.25% BSA from incubates of adipose tissue cells did not interfere with the standard curve. The analytical interference from different factors that could be used in studies of lipolysis was investigated. No interference was observed up to the following concentrations: 5 microM epinephrine, 5 microM norepinephrine, 80 microM isoproterenol, 1 mM insulin, 2.5 mM propranolol, 5 mM phentolamine, and 5 microM ascorbate. Results obtained with the present assay were highly correlated (r = 0.997) with those obtained by a 260-times less sensitive spectrophotometric kit method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496670 TI - Synthesis of 27-hydroxycholesterol in rat liver mitochondria: HPLC assay and marked activation by exogenous cholesterol. AB - Sterol 27-hydroxylase, the mitochondrial enzyme that catalyzes the first step in oxidation of the sterol side chain in hepatic bile acid synthesis, also catalyzes the synthesis of 27-hydroxycholesterol from cholesterol. We have developed a high performance liquid chromatography (HPLC) assay for this enzyme, using either endogenous or exogenous cholesterol as substrate and cholesterol oxidase to convert 27-hydroxycholesterol to 4-cholesten-27-hydroxy-3-one. The alpha,beta unsaturated ketone product was separated by normal phase HPLC and quantitated via absorption at 240 nm. Addition of cholesterol dissolved in 2-hydroxypropyl-beta cyclodextrin to the assay mixture raised the enzyme activity of rat liver mitochondria more than 10-fold. 2-Hydroxypropyl-beta-cyclodextrin itself was partially effective, apparently by making more endogenous cholesterol accessible to the enzyme. Availability of cholesterol to the enzyme limits synthesis of 27 hydroxycholesterol in rat liver. Using our assay to simultaneously determine the activities of cholesterol 7 alpha-hydroxylase and cholesterol 27-hydroxylase in rat liver homogenates, we demonstrated that the two enzymes are separately regulated. PMID- 8496671 TI - Detection of hormone-sensitive lipase in various tissues. I. Expression of an HSL/bacterial fusion protein and generation of anti-HSL antibodies. AB - Hormone-sensitive lipase (HSL) is an intracellular neutral lipase found in a variety of tissues, but primarily in adipose and steroidogenic tissues, that hydrolyzes triglycerides and cholesteryl esters. In the present studies, a portion of rat HSL cDNA was subcloned into a pET expression system and the resulting recombinant fusion protein was over-expressed in E. coli. The approximately 26 kD HSL/fusion protein was used to generate polyclonal antibodies in rabbits that recognize intact HSL (84 kD) in rat adipose tissue, ovary, adrenal, testis, heart, and lung, as well as in human adipose tissue. In addition, there was an approximately 89 kD protein observed in all rat tissues expressing the 84 kD protein. Unique to testes, there was an immunoreactive protein of approximately 102 kD in sexually immature rats, and additional immunoreactive proteins of approximately 113 kD and approximately 127 kD in sexually mature rats. The anti-HSL/fusion protein antibodies could remove approximately 60-80% of total neutral cholesterol esterase activity from extracts of rat adipose tissue and immunoprecipitated a single 84 kD protein after labeling of adipocytes with [32P]orthophosphate. The incorporation of 32P into the 84 kD HSL protein was stimulated 4-fold by incubation of adipocytes with isoproterenol. The half life of [35S]methionine-labeled HSL was approximately 4 h in normal rat adipocytes. The production of an HSL/fusion protein and generation of antibodies that recognize native HSL should be valuable tools in exploring the mechanisms regulating the expression of HSL activity and the function and localization of its immunoreactive proteins. PMID- 8496672 TI - Polyclonal antibody-based immunoradiometric assay for quantification of cholesteryl ester transfer protein. AB - Cholesteryl ester transfer protein (CETP) catalyzes the transfer of neutral lipids among plasma lipoproteins and in this way plays a prominent role in cholesterol metabolic routing and, thus, probably for atherosclerosis. Studies of this important protein in various clinical settings require the ability to accurately quantify CETP in plasma. In order to gain access to such a capability, an immunoradiometric assay (IRMA) for quantification of CETP was developed. CETP was purified from human plasma to apparent homogeneity and used for raising anti CETP antibodies in rabbits. The specificity of the polyclonal antiserum obtained was demonstrated by inhibition assays and immunoblot analysis. Before use in the CETP-IRMA, the antibodies were affinity-purified by chromatography on CETP Sepharose. Sensitivity of the CETP-IRMA was 0.1 ng, and intra- and interassay coefficients of variation were 2.9 and 8.0%, respectively. In 30 normolipidemic healthy subjects, the mean (+/- SD) CETP concentration was 1.1 (+/- 0.22) micrograms/ml of plasma; individual values ranged from 0.644 to 1.694 micrograms CETP/ml and agreed well with measurements of CETP activity of the same samples (r = 0.85). PMID- 8496673 TI - 1992 Aspen Bile Acid/Cholesterol/Lipoprotein Conference. Report of a conference. PMID- 8496674 TI - Reconstitution of the functional receptors for murine and human interleukin 5. AB - The murine interleukin 5 receptor (mIL-5R) is composed of two distinct subunits, alpha and beta. The alpha subunit (mIL-5R alpha) specifically binds IL-5 with low affinity. The beta subunit (mIL-5R beta) does not bind IL-5 by itself, but forms the high-affinity receptor with mIL-5R alpha. mIL-5R beta has been revealed to be the mIL-3R-like protein, AIC2B which is shared with receptors for IL-3 and granulocyte/macrophage colony-stimulating factor. We demonstrated here the reconstitution of the functional receptors for murine and human IL-5 on the mouse IL-2-dependent cell line, CTLL-2. CTLL-2 was transfected with the cDNAs for mIL 5R alpha and/or AIC2B. Only CTLL-2 transfectant expressing both mIL-5R alpha and AIC2B expressed the high-affinity receptor and proliferated in response to murine IL-5. Then CTLL-2 was transfected with the cDNAs for hIL-5R alpha and/or KH97 (beta c), the human homologue of AIC2B. Though beta c did not contribute much to binding affinity of hIL-5R, only CTLL-2 transfectant expressing both hIL-5R alpha and beta c proliferated in response to human IL-5. These results showed that the beta subunit is indispensable in IL-5 signal transduction. We further investigated the function of IL-5-specific alpha subunit in transmitting IL-5 signals. Mutant mIL-5R alpha, which lacks its whole cytoplasmic domain, was transfected into mouse IL-3-dependent cell line, FDC-P1 expressing AIC2B intrinsically. The resulting transfectant did not respond to IL-5, though the transfectant expressed the high-affinity IL-5R, indicating that the cytoplasmic portion of the alpha subunit also has some important role in IL-5-mediated signal transduction. PMID- 8496675 TI - Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells. AB - A previous report showed that the proliferative response of helper T cells to class II major histocompatibility complex (MHC)-restricted antigens can be inhibited by analogues of the antigen, which act as T cell receptor (TCR) antagonists. Here we define and analyze peptide variants that antagonize various functions of class I MHC-restricted cytotoxic T lymphocyte (CTL) clones. Of 64 variants at individual TCR contact sites of the Kb-restricted octamer peptide ovalbumin257-264 (OVAp), a very high proportion (40%) antagonized lysis by three OVAp-specific CTL clones. This effect was highly clone specific, since many antagonists for one T cell clone have differential effects on another. We show that this inhibition of CTL function is not a result of T cell-T cell interaction, precluding veto-like phenomena as a mechanism for antagonism. Moreover, we present evidence for direct interaction between the TCR and antagonist-MHC complexes. In further analysis of the T cell response, we found that serine esterase release and cytokine production are susceptible to TCR antagonism similarly to lysis. Ca2+ flux, an early event in signaling, is also inhibited by antagonists but may be more resistant to the antagonist effect than downstream responses. PMID- 8496676 TI - The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg induced granulomatous inflammation. AB - Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1 alpha in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1 alpha was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1 alpha production (< 1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1 alpha production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1 alpha production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1 alpha at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1 alpha in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1 alpha production to macrophages within granulomas. Treatment of mice with rabbit anti mouse MIP-1 alpha antibodies significantly decreased 8-d primary granuloma formation (> 40%) when compared with control mice. Anti-MIP-1 alpha sera also decreased vigorous (> 20%), but not modulated granuloma formation. These findings demonstrate that MIP-1 alpha contributes to cellular recruitment during schistosome egg granuloma formation. PMID- 8496677 TI - High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease. AB - The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA) A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1. PMID- 8496678 TI - Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections. AB - The group B Streptococcus, an important cause of invasive infections in the neonate, is classified into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule. Since the capsule is a known virulence factor, it has been extensively studied, in particular in type III strains, which cause the majority of invasive infections. Two cell surface proteins, alpha and beta, have also been studied in detail since they confer protective immunity, but these proteins are usually not expressed by type III strains. We describe here a cell surface protein, designated protein Rib (resistance to proteases, immunity, group B), that confers protective immunity and is expressed by most strains of type III. Protein Rib was first identified as a distinct 95-kD protein in extracts of a type III strain, and was purified to homogeneity from that strain. Rabbit antiserum to protein Rib was used to demonstrate that it is expressed on the cell surface of 31 out of 33 type III strains, but only on 1 out of 25 strains representing the other three serotypes. Mouse protection tests showed that antiserum to protein Rib protects against lethal infection with three different strains expressing this antigen, including a strain representing a recently identified high virulence type III clone. Protein Rib is immunologically unrelated to the alpha and beta proteins, but shares several features with the alpha protein. Most importantly, the NH2 terminal amino acid sequences of the Rib and alpha proteins are identical at 6 out of 12 positions. In addition, both protein Rib and the alpha protein are relatively resistant to trypsin (and Rib is also resistant to pepsin) and both proteins vary greatly in size between different clinical isolates. Finally, both protein Rib and the alpha protein exhibit a regular ladderlike pattern in immunoblotting experiments, which may reflect a repetitive structure. Taken together, these data suggest that the Rib and alpha proteins are members of a family of proteins with related structure and function. Since protein Rib confers protective immunity, it may be valuable for the development of a protein vaccine against the group B Streptococcus, an encapsulated bacterium. PMID- 8496679 TI - Histoplasma capsulatum modulates the acidification of phagolysosomes. AB - The phagolysosome is perhaps the most effective antimicrobial site within macrophages due both to its acidity and to its variety of hydrolytic enzymes. Few species of pathogens survive and multiply in these vesicles. However, one strategy for microbial survival would be to induce a higher pH within these organelles, thus interfering with the activity of many lysosomal enzymes. Altering the intravesicular milieu might also profoundly influence antigen processing, antimicrobial drug delivery, and drug activity. Here we report the first example of an organism proliferating within phagolysosomes that maintain a relatively neutral pH for a sustained period of time. We inoculated P388D1 macrophages with fluorescein isothiocyanate (FITC)-labeled Histoplasma capsulatum or zymosan. Using the ratio of fluorescence excitations at 495 and 450 nm, we determined that vesicles containing either virulent or avirulent FITC-labeled H. capsulatum yeasts had a pH one to two units higher than vesicles containing either zymosan or methanol-killed H. capsulatum. The difference in pH remained stable for at least 5.5 h postinoculation. Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h. Many agents raise the pH of multiple vesicles within the same cell. In contrast, H. capsulatum affects only the phagolysosome in which it is located; during coinoculation of cells with unlabeled Histoplasma and labeled zymosan, organelles containing zymosan still acidified normally. Similarly, unlabeled zymosan had no influence on the elevated pH of vesicles housing labeled Histoplasma. Thus, zymosan and Histoplasma were segregated into separate phagolysosomes that responded independently to their phagocytized contents. This localized effect might reflect an intrinsic difference between phagosomes housing the two particle types, active buffering by the microbe, or altered ion transport across the phagolysosomal membrane such that acidification is inhibited. PMID- 8496680 TI - Persistent calcium elevation correlates with the induction of surface immunoglobulin-mediated B cell DNA synthesis. AB - Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ([Ca2+]i). These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low level but persistent sustained or cyclic elevations in [Ca2+]i. In marked contrast, early and nonsustained elevations in [Ca2+]i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran anti-Ig conjugate which induced very high levels of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in [Ca2+]i as detected by flow cytometry. Finally, B cells from X linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in [Ca2+]i, but do not show persistent calcium elevations. These data suggest that the rapid and large increases of [Ca2+]i seen in lymphocytes within seconds after antigen receptor ligation may be associated with entry in G1, whereas low-level but persistent elevations may be the hallmark of a cell destined to synthesize DNA. PMID- 8496681 TI - Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients. AB - Rheumatoid arthritis (RA) represents a heterogenous disease characterized by chronic polyarthritis. Most patients with adult RA inherit HLA-DR4 or -DR1 major histocompatibility complex (MHC) genes. While the molecular basis for this genetic predisposition is unknown, the major function of these MHC-encoded molecules is to present peptides to T lymphocytes. It is hypothesized that an endogenous or environmental antigen initiates a MHC-restricted immune response mediated by T lymphocytes, which is followed by a chronic inflammatory reaction involving many cell types. In chronic RA, previous or ongoing antigenic activation might result in detectable skewing of the peripheral alpha/beta T cell receptor (TCR) repertoire. Here we demonstrate a marked expansion of V alpha 12.1 bearing CD8+ T cells in the peripheral blood (mean, 22%; range, 10-43%) of > 15% of RA patients. A major proportion of these patients shared HLA-DQ2 in addition to the expected high frequency DR1 and DR4 alleles. Detailed molecular analysis in three of the RA patients with elevated V alpha 12.1+ T cells identified repeated TCR alpha chain sequences consistent with clonal V alpha 12.1+,CD8+ T cell expansion. In addition to shared TCR V alpha 12.1 germline gene usage among unrelated subjects, a conserved J alpha motif was also detected. Together, these results suggest an antigen-driven mechanism of T cell expansion in these patients and may offer a new approach in examining specific antigen that stimulate T cells in RA. PMID- 8496682 TI - Class I molecules retained in the endoplasmic reticulum bind antigenic peptides. AB - We isolated major histocompatibility complex (MHC)-specific viral peptides from cells infected with influenza virus in the continuous presence of the drug brefeldin A, which blocks exocytosis of newly synthesized MHC class I molecules. MHC-specific peptides were also isolated from cells expressing mouse Kd class I MHC molecules whose cytoplasmic domain was substituted by that of the adenovirus E3/19K glycoprotein. This molecule was retained in an intracellular pre-Golgi complex compartment as demonstrated by immunocytochemical and biochemical means. Since we show that intracellular association of antigenic peptides with such retained class I molecules is necessary for their isolation from cellular extracts, this provides direct evidence that naturally processed peptides associate with class I MHC molecules in an early intracellular exocytic compartment. PMID- 8496683 TI - KBF1 (p50 NF-kappa B homodimer) acts as a repressor of H-2Kb gene expression in metastatic tumor cells. AB - Downregulation of major histocompatibility complex class I expression is causally related to high malignancy and low immunogenicity of certain murine tumors. In this study, we have analyzed the roles of the nuclear factors KBF1/p50 and p65 in regulation of class I expression in high and low metastatic tumor cells. Low class I-expressing cells show at higher levels of KBF1/p50 and NF-kappa B (p50/p65) binding activity than high class I-expressing cells. However, an excess of KBF1 over NF-kappa B is observed in low expressing cells, while an excess of NF-kappa B over KBF1 is observed in high expressing cells. Stable transfection of a p65 expression vector into low class I-expressing cells activated H-2 transcription and cell surface expression, while stable transfection of p50 expression vector into high expressing cells suppressed H-2Kb transcription and cell surface expression. Our studies suggest that KBF1 has the potential of downregulating class I gene expression, whereas dimers containing the p65 subunit are activators of class I gene expression. PMID- 8496684 TI - Transcription of the interleukin 4 gene is regulated by multiple promoter elements. AB - Activation of T helper cell 1 (Th1) and Th2 results in transcription of the interleukin 2 (IL-2) and IL-4 cytokine genes, respectively. Whereas many of the regulatory elements and factors responsible for IL-2 transcription in T cells are well defined, little is known about parallel mechanisms that drive transcription of the IL-4 gene. Here we have analyzed the murine IL-4 promoter, both in vivo and in a Th2 clone. 3 kb of IL-4 upstream sequence is shown to be sufficient to achieve tissue-specific and inducible expression of a thymidine kinase reporter gene in vivo in a manner that mirrors the expression of endogenous IL-4. Tissue specific and inducible expression is also demonstrated in a Th2 clone, but not in a B cell line. Deletional and mutational analysis of the IL-4 promoter demonstrated that sequences from -100 to -28 were necessary for a transcriptional response to Concanavalin A or anti-CD3 monoclonal antibody. An overlapping, yet smaller region, spanning the sequences from -60 to -28 bp was shown to be required for the response to ionomycin. Mutation of an 8-bp region from -43 to 35 of the IL-4 promoter completely abrogated IL-4 gene transcription in response to all stimuli tested. In addition, our results show that the effects of the immunosuppressive agent Cyclosporin A map to the same DNA sequences as the positive control elements. These results identify DNA sequences that are functionally important for the control of IL-4 gene transcription both in vivo and in vitro. Although these sequences are highly conserved in the human and murine IL-4 genes, they are largely not present in the IL-2 enhancer complex. Thus, cytokine-specific cis-acting elements may be one mechanism by which these two cytokine genes are differentially regulated. PMID- 8496685 TI - Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. AB - We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA. Thus, the half-life of the molecule was reduced from approximately 30 to approximately 17 min in the presence of 50 micrograms/ml of thalidomide. Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected. Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha synthesis at distinct points of the cytokine biosynthetic pathway. These observations provide an explanation for the synergistic effects of these drugs. The selective inhibition of TNF-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact. PMID- 8496686 TI - An evaluation of the potential to use tumor-associated antigens as targets for antitumor T cell therapy using transgenic mice expressing a retroviral tumor antigen in normal lymphoid tissues. AB - A major obstacle to the development of T cell therapy for the treatment of human tumors has been the difficulty generating T cells specifically reactive with the tumor. Most of the characterized human tumor antigens have been classified as tumor associated, because of demonstrable expression at low levels in some normal cells, and thus have not been extensively studied as potential targets of a therapeutic immune response. However, the quantitative difference in expression of such antigens between the tumor and normal cells might permit the generation of antigen-specific T cells capable of selective antitumor and not autoimmune activity. To address this issue, transgenic (TG) mice were generated that expressed low levels of Friend murine leukemia virus (FMuLV) envelope protein in lymphoid cells under the control of an immunoglobulin promoter. This protein is expressed at high levels by a Friend virus-induced erythroleukemia of C57BL/6 (B6) origin, FBL, and has been shown to serve as an efficient tumor-specific rejection antigen in B6 mice. The env-TG mice were tolerant to envelope, as reflected by the failure to detect an envelope-specific response after in vivo priming and in vitro stimulation with preparations of FMuLV envelope. However, adoptively transferred envelope-specific T cells from immunized non-TG B6 mice mediated complete eradication of FBL tumor cells in TG mice, and did not induce detectable autoimmune damage to TG lymphoid tissues. The transferred immune cells were not permanently inactivated in the TG mice, since donor T cells responded to envelope after removal from the TG mice. The lack of autoimmune injury did not reflect inadequate expression of envelope by TG lymphocytes for recognition by T cells, since TG lymphocytes functioned effectively in vitro as stimulators for envelope-specific T cells. The results suggest that this and analogous strains of TG mice may prove useful for elucidating principles for the generation and therapeutic use of tumor-reactive T cells specific for tumor-associated antigens. PMID- 8496687 TI - Polymorphisms in pockets of major histocompatibility complex class I molecules influence peptide preference. AB - The set of peptides that is bound by a given major histocompatibility complex class I product can be described by one or two properly spaced anchor residues, and two properly spaced peptide termini, approximately 8-10 residues apart. Using radiolabeled peptide libraries, we examined whether mutations in those "pockets" in class I Kb molecules that do not seem critically involved in the interaction with the peptide anchor residues, do exert an effect on the set of preferred peptides. We find that mutations in all the pockets found in the structure of Kb have a significant effect on the peptide preference of the molecule, and their recognition by cytotoxic T cells. Alterations in substrate specificity are also observed for mutations involving residues that interact with main chain atoms in both peptide termini. These findings challenge a static view of the interaction of peptide termini with their respective pockets in the class I molecule, and imply a role for the minor pockets in peptide selectivity. PMID- 8496688 TI - Mycobacterial virulence. Virulent strains of Mycobacteria tuberculosis have faster in vivo doubling times and are better equipped to resist growth-inhibiting functions of macrophages in the presence and absence of specific immunity. AB - The kinetics of growth of two virulent strains of mycobacteria (M. tuberculosis Erdman and M. tuberculosis H37Rv) and two attenuated strains (M. tuberculosis H37Ra and M. bovis Bacillus Calmette-Guerin [BCG]) were studied in the lungs, livers, spleens, and kidneys of severe combined immunodeficient (SCID) mice and of their coisogenic CB-17 immunocompetent counterparts. It was found, in keeping with the findings of earlier investigators (Pierce, C. H., R. J. Dubos, and W. B. Schaefer. 1953. J. Exp. Med. 97:189.), that in immunocompetent mice, virulent organisms grew progressively only in the lungs, whereas the growth of attenuated organisms was controlled in all organs. In SCID mice, in contrast, virulent mycobacteria grew rapidly and progressively in all organs, as did BCG, although at a slower rate. However, H37Ra failed to grow progressively in any organs of SCID mice, unless the mice were treated with hydrocortisone. In fact, hydrocortisone treatment enabled virulent, as well as attenuated, organisms to grow strikingly more rapidly in all organs of SCID mice and in all organs of CB 17 mice. A histological study showed that in SCID mice, multiplication of mycobacteria in the liver occurs in the cytoplasm of macrophages in granulomas and presumably in macrophages in other organs. It is suggested, therefore, that the macrophages of SCID mice possess a glucocorticoid-sensitive mycobacterial mechanism that prevents virulent and avirulent mycobacteria from expressing their true minimal doubling times. In the absence of this mechanism in the lungs of hydrocortisone-treated SCID mice, the doubling times of Erdman, H37Rv, BCG, and H37Ra were 17.7, 17.4, 44.6, and 98.6 h, respectively. The possible importance of a rapid multiplication rate for mycobacterial virulence is discussed. PMID- 8496689 TI - Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targetting and results in a verotoxin 1-like disease in pigs. AB - All members of the verotoxin (VT) family specifically recognize globo-series glycolipids on the surface of susceptible cells. Those toxins that are associated with human disease, VT1, VT2, and VT2c, bind to globotriaosyl ceramide (Gb3) while VT2e, which is associated with edema disease of swine, binds preferentially to globotetraosyl ceramide (Gb4). We were recently able to identify, using site directed mutagenesis, amino acids in the binding subunit of these toxins that are important in defining their glycosphingolipid (GSL) binding specificity (Tyrrell, G. J., K. Ramotar, B. Boyd, B. W. Toye, C. A. Lingwood, and J. L. Brunton. 1992. Proc. Natl. Acad. Sci. USA. 89:524). The concomitant mutation of Gln64 and Lys66 in the VT2e binding subunit to the corresponding residues (Glu and Gln, respectively) found in VT2 effectively converted the GSL binding specificity of the mutant toxin from Gb4 to Gb3 in vitro. We now report that the altered carbohydrate recognition of the mutant toxin (termed GT3) has biological significance, resulting in a unique disease after intravascular injection into pigs as compared with classical VT2e-induced edema disease. The tissue localization of radiolabeled GT3 after intravascular injection was elevated in neural tissues compared with VT2e accumulation, while localization of GT3 to the gastrointestinal tract was relatively reduced. Accordingly, the pathological lesions after challenge with GT3 involved gross edema of the cerebrum, cerebellum, and brain stem, while purified VT2e caused hemorrhage and edema of the cerebellum, and submucosa of the stomach and large intestine. In addition, both radiolabeled toxins bound extensively to tissues not directly involved in the pathology of disease. VT2e, unlike GT3 or VT1, bound extensively to red cells, which have high levels of Gb4. The overall tissue distribution of VT2e was thus found to be influenced by regional blood flow to each organ and not solely by the Gb4 levels of these tissues. Conversely, the distribution of GT3 (and VT1), which cleared more rapidly from the circulation, correlated with respective tissue Gb3 levels rather than blood flow. These studies indicate the primary role of carbohydrate binding specificity in determining systemic pathology, suggest that the red cells act as a toxin carrier in edema disease, and indicate that red cell binding does not protect against the pathology of systemic verotoxemia. PMID- 8496690 TI - Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. AB - Resident pulmonary alveolar macrophages (PAM) play an important role in the maintenance of immunological homeostasis in the lung via downmodulation of local T cell responses in the steady state. The present study demonstrates that this pathway for T cell suppression is reversible via granulocyte/macrophage colony stimulating factor (GM-CSF). Thus, freshly isolated PAM strongly inhibit mitogen induced T cell proliferation, and pretreatment of the PAM with cytokine-rich lung conditioned medium (LCM) generated by exposure of lung to bacterial lipopolysaccharide (LPS) abrogated this suppressive activity. LCM from lungs of normal and athymic nude mice exhibited identical activity. Moreover, the PAM modulating activity of LCM was inhibited by blocking antibody specific for GM CSF, and the activity of LCM could be reproduced by recombinant GM-CSF. This suggests that secretion of GM-CSF by mesenchymal cells and/or macrophages under stimulation from agents such as LPS provides a potential mechanism for upregulation of local T cell responsiveness during acute inflammation. In addition, experiments with a range of cytokines indicated that interleukin 4, transforming growth factor beta 1 and tumor necrosis factor alpha (TNF-alpha) exhibited weaker (but significant) modulatory effects on PAM, and (in the case of TNF-alpha) amplified the effects of GM-CSF. PMID- 8496691 TI - Presentation of numerous viral peptides to mouse major histocompatibility complex (MHC) class I-restricted T lymphocytes is mediated by the human MHC-encoded transporter or by a hybrid mouse-human transporter. AB - The major histocompatibility complex-encoded transporter associated with antigen processing (TAP) is required for the efficient presentation of cytosolic antigens to class I-restricted T cells. TAP is thought to be formed by the interaction of two gene products, termed TAP1 and TAP2. We find that TAPs consisting either of human subunits, or mouse TAP1 and human TAP2, facilitate the presentation of numerous defined viral peptides to mouse class I-restricted T cells. As human and mouse TAP2 and TAP1 differ in 23 and 28% of their residues, respectively, this indicates that TAP1 and TAP2 can form a functional complex with partners considerably different from those they coevolved with. Moreover, these findings indicate that widely disparate TAPs facilitate delivery of the same peptides to class I molecules. These findings suggest that TAP polymorphism does not greatly influence the types of peptides presented to the immune system. PMID- 8496692 TI - Identification of a recombinogenic major histocompatibility complex Q gene with diverse alleles. AB - Structural diversity enables class Ia molecules to present a diverse repertoire of peptides to the T cell receptor. This diversity is thought to be generated by recombinations between class I genes. We have found that two class Ib Q2 alleles exhibit extremely high sequence diversity, even higher than class Ia alleles. Clustered nucleotide differences between Q2b and Q2k suggest that this sequence diversity was generated by microrecombinations between Q2 genes and other class I genes. The relatively high expression of Q2b in the thymus may be significant and perhaps suggests a novel role for a Q2b product in the education and selection of the T cell repertoire. PMID- 8496693 TI - Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. AB - The human cytokine interferon-inducible protein 10 (IP-10) is a small glycoprotein secreted by activated T cells, monocytes, endothelial cells, and keratinocytes, and is structurally related to a family of chemotactic cytokines called chemokines. Although this protein is present in sites of delayed-type hypersensitivity reactions and lepromatous leprosy lesions, the biological activity of IP-10 remains unknown. We report here that recombinant human IP-10 stimulated significant in vitro chemotaxis of human peripheral blood monocytes but not neutrophils. Recombinant human IP-10 also stimulated chemotaxis of stimulated, but not unstimulated, human peripheral blood T lymphocytes. Phenotypic analysis of the stimulated T cell population responsive to IP-10 demonstrated that stimulated CD4+ and CD29+ T cells migrated in response to IP 10. This resembles the biological activity of the previously described T cell chemoattractant RANTES. Using an endothelial cell adhesion assay, we demonstrated that stimulated T cells pretreated with optimal doses of IP-10 exhibited a greatly enhanced ability to bind to an interleukin 1-treated endothelial cell monolayer. These results demonstrate that the IP-10 gene encodes for an inflammatory mediator that specifically stimulates the directional migration of T cells and monocytes as well as potentiates T cell adhesion to endothelium. PMID- 8496694 TI - Complement-mediated adipocyte lysis by nephritic factor sera. AB - Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage. PMID- 8496695 TI - Spinal dural arteriovenous malformations. PMID- 8496696 TI - Can basic science help improve arm function in C5 tetraplegia? PMID- 8496697 TI - Insurance benefits coverage for persons with spinal cord injuries: determining differences across payors. AB - This investigation represents a preliminary step in determining differences in benefits coverage among three types of rehabilitation insurance payors (Catastrophic payors, which include Automobile No-Fault and Workers' Disability Compensation; Medicaid; and Third-party private payors). Subjects in this study were 122 spinal cord injury (SCI) outpatients who received their initial rehabilitation at the University of Michigan Medical Center and at the Rehabilitation Institute of Michigan. Insurance benefits received by them were examined across the following areas: accessible housing, transportation, personal attendant care services, professional outpatient services and adapted equipment. Results indicated differences across the three payors, with catastrophically sponsored SCI outpatients receiving more benefits than SCI outpatients sponsored by public Medicaid or by private third-party insurance. Implications and recommendations for further studies are briefly discussed. PMID- 8496698 TI - The spectrum of neurofibromatosis: neurologic manifestations with malignant transformation. AB - Neurofibromatosis is an uncommon cause of tetraplegia. Spinal cord compression in association with brachial plexus involvement is rare. A case of neurofibromatosis with malignant transformation illustrates the neurologic features associated with this condition. Malignant transformation of a neurofibroma should always be considered in patients with recurrent lesions or progressive neurologic dysfunction. PMID- 8496699 TI - ASIS Annual Meeting. Abstracts. PMID- 8496700 TI - The role of receptor binding in drug discovery. AB - Radioligand receptor binding has been used extensively to identify and characterize a host of receptors and enzymes targeting virtually every therapeutic area. Many drug discovery programs have been based on the utilization of radioligand receptor binding technology to identify lead compounds which interact with receptors likely to be important in neuronal, immunological, gastrointestinal, and cardiovascular function/dysfunction. There are several obvious advantages to using in vitro receptor binding as a first level screen when compared to in vivo pharmacometric screens. Scientifically, the structure activity data generated in binding assays is a direct reflection of the ligand/receptor interaction minus the complications which result from secondary events, bioavailability, and pharmacodynamic issues. Technically, the binding studies require only a small amount of test compound (< or = 1 mg), while whole animal studies routinely need gram quantities. Similarly, only a small amount of tissue is required, compared with the cost of purchase and maintenance of live animals for in vivo screening. Supply and labor costs are drastically reduced due to the limited volume and test tube based technology of receptor binding. For these reasons receptor binding assays have been utilized with considerable success to discover site specific lead compounds in virtually every therapeutic area. PMID- 8496701 TI - Bisamides from Aglaia species: structure analysis and potential to reverse drug resistance with cultured cells. AB - The structure of pyramidatine [1], a new bisamide alkaloid from leaves of Aglaia pyramidata, was determined through extensive nmr studies, including homonuclear COSY, NOESY, APT, HETCOR, and selective INEPT techniques. Revision of the 13C-nmr assignment of piriferine [2], an alkaloid previously isolated from A. pirifera, was achieved by examination of several 2D nmr spectra (homonuclear COSY, NOESY, and HETCOR) and confirmed by selective INEPT nmr experiments. Evaluation of the cytotoxic potential of the two alkaloids, along with two other bisamides from Aglaia odorata, odorine [3] and 5'-epi-odorine [4], was carried out in eleven human cancer cell lines. None of these bisamides showed significant cytotoxicity. Nevertheless, piriferine [2], odorine [3], and 5'-epi-odorine [4] were found to inhibit the growth of the vinblastine-resistant KB cells by enhancing the anticancer activity of vinblastine. PMID- 8496702 TI - Sesquiterpene-derived metabolites from the deep water marine sponge Poecillastra sollasi. AB - Six sesquiterpene-derived compounds, 1-6, which we call sollasins a-f, have been isolated from a deep water specimen of the sponge Poecillastra sollasi. The structures were elucidated by comparison of spectral data to related metabolites and confirmed using spectroscopic methods. The compounds inhibit the growth of the pathogenic fungi Candida albicans and Cryptococcus neoformans and the P-388 and A-549 tumor cell lines. Compounds 3 and 4 show weak inhibition of binding of [125I] angiotensin II to rat aorta smooth muscle cell membranes. PMID- 8496703 TI - New jaeschkeanadiol derivatives from Ferula jaeschkeana. AB - Two new jaeschkeanadiol derivatives have been isolated from Ferula jaeschkeana rhizomes. These have been identified as a dichloro compound, jaeschkenol [1], and 2 alpha,3 alpha-dihydroxy-4-keto-5 alpha-p-hydroxybenzoyl-jaeschkeanadiol [2], on the basis of spectral data and the X-ray analysis of the former. PMID- 8496704 TI - A rapid screening method for artemisinin and its congeners using ms/ms: search for new analogues in Artemisia annua. AB - A rapid screening method based on tandem mass spectrometry (ms/ms) is described for artemisinin-related compounds present in complex matrices. These compounds produce abundant ammonium adducts, [M + NH4]+, using ammonia desorption chemical ionization (dci), and dissociation of the mass-selected adducts yields the protonated molecules, [M + H]+, which subsequently eliminate characteristic neutral molecules (H2O, CO, HCO2H, HOAc). Neutral loss ms/ms scans which are selective for different elimination reactions were used in order to screen for groups of related analogues present in a crude hexane extract of Artemisia annua. Comparison of ms/ms product spectra of known Artemisia compounds with those of the new analogues provided information on the functional groups and the molecular weights of the new compounds present in the plant, and tentative structures are suggested. PMID- 8496705 TI - Tricolorin A, major phytogrowth inhibitor from Ipomoea tricolor. AB - The allelopathic potential of Ipomoea tricolor (Convolvulaceae), used in Mexican traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of organic extracts on seedling growth of Amaranthus leucocarpus and Echinochloa crus-galli. Bioactivity-directed fractionation of the active CHCl3 extract led to the isolation of the allelopathic principle, which turned out to be a mixture of the so-called "resin glycosides" of convolvulaceous plants. The structure of tricolorin A, the major phytogrowth inhibitor present in the active fraction, was elucidated as (11S)-hydroxyhexadecanoic acid 11-O-alpha L-rhamnopyranosyl-(1-->3)-O-alpha-L-[2-O-(2S-methylbutyryl)-4 -O- (2S methylbutyryl)] rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D fucopyran oside- (1,3"-lactone)[1], based on chemical methods and spectral analysis including 1H-1H COSY, 1H-13CHETCOR, long range 1H-13C COLOC, and selective INEPT experiments. Bioassays showed that radicle elongation of the two weed seedlings tested was inhibited by tricolorin A [1] with IC50 values ranging from 12 to 37 microM. Staphylococcus aureus was sensitive to compound 1 with an MIC value of 1.8 micrograms/ml. Significant cytotoxic activity against cultured P 388 and human breast cancer cells (ED50 2.2 micrograms/ml) was demonstrated for compound 1, and it also inhibited phorbol 12,13-dibutyrate binding using calf brain homogenate as a source of protein kinase C (IC50 43 microM). PMID- 8496706 TI - Structure and stereochemistry of pectinolides A-C, novel antimicrobial and cytotoxic 5,6-dihydro-alpha-pyrones from Hyptis pectinata. AB - By bioactivity-directed fractionation, three new antimicrobial and cytotoxic 5,6 dihydro-alpha-pyrones, pectinolides A-C, have been isolated from Hyptis pectinata (Lamiaceae). The absolute stereochemistry of pectinolide A [1] was established as 6S-[(3S-acetyloxy)-1Z-heptenyl]-5S-(acetyloxy)-5 ,6-dihydro-2H-pyran-2-one, on the basis of spectral, chiroptical, and chemical evidence. The structures of pectinolides B [2] and C [3] were determined as the monodeacetylated forms of 1 by comparison of their spectral data and chemical correlation with the prototype compound. Staphylococcus aureus and Bacillus subtilis were sensitive to pectinolide A [1] in the concentration range of 6.25-12.5 micrograms/ml. Compounds 1-3 exhibited significant cytotoxic activity (ED50 < 4 micrograms/ml) against a variety of tumor cell lines. PMID- 8496707 TI - Karsoside and scropolioside D, two new iridoid glycosides from Scrophularia ilwensis. AB - Two new iridoid glycosides, karsoside [1] and scropolioside D [2], were isolated from the aerial parts of Scrophularia ilwensis. Their structures were elucidated on the basis of chemical and spectral data as 6'-O-(beta-D-xylopyranosyl) methylcatalpol and 6-O-[(2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L rhamnopyranosyl]- catalpol, respectively. Additionally, four known iridoids (aucubin, harpagide, 8-O-acetylharpagide, and ajugol), a phenylpropanoid glycoside (angoroside C), and two flavonoids (quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside) were isolated and identified. PMID- 8496708 TI - Problems with rating scales for multiple sclerosis: a novel approach--the CAMBS score. AB - Current rating scales for multiple sclerosis are unsatisfactory because they score each patient's condition without indicating the clinical context in which that score has been obtained. The Cambridge Multiple Sclerosis Basic Score (CAMBS) offers a solution to this problem by recording current status in the context of the clinical course. CAMBS distinguishes disability from handicap and indicates the independent contribution of relapse and progression to current clinical activity. Single scores of between 1 and 5 are assigned to each of these indices, giving a simple four component analysis for each clinical encounter, e.g. disability 3; relapse 1; progression 2; handicap 1. PMID- 8496709 TI - Insula and aphasia. AB - A 59-year-old woman developed impaired speech initiation as the result of a left anterior insular infarct. Findings from this case suggest that dominant hemisphere anterior insular lesions impair the speech initiation loop. PMID- 8496710 TI - Mitochondrial encephalomyopathy, lactic acidosis and stroke in adults: two cases. AB - Two previously healthy women are described who in their late thirties suffered transient strokelike episodes, consisting of initial headache and vomiting, with various subsequent neurological signs that were only partially reversible. Investigations revealed elevated serum creatine kinase, lactic acidosis, hypertriglyceridaemia, and ragged red fibres in the muscle biopsy specimens. In both patients in vitro studies were performed on intact muscle mitochondria and muscle homogenate. Only in one was a mitochondrial defect found, located at the level of coenzyme Q. We conclude that these patients suffered from adult-onset mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS syndrome). Although the syndrome is often associated with long-standing neurological multisystem disease from childhood onwards, it should also be suspected in adults with strokelike signs of otherwise unexplained origin. PMID- 8496711 TI - Partial complex epileptic seizures provoked by ingestion of alcohol. AB - The authors describe three cases of partial complex epileptic seizures precipitated by alcohol consumption. No other causative factor was found. Brain imaging was normal. The role of alcohol in precipitating this type of seizures is discussed. PMID- 8496712 TI - Early symptoms and outcome of Listeria monocytogenes rhombencephalitis: 14 adult cases. AB - Listeria monocytogenes rhombencephalitis has never been studied in a significant group of patients. We describe 14 adult cases who were seen over a 10-year period. A biphasic illness was characteristic: (1) prodromes (5-15 days) with malaise, fatigue, headache, nausea or vomiting, and fever; (2) cranial nerve palsy with facial palsy, diplopia, dysphagia, dysarthria, usually multiple. Meningism and hemi- or tetraparesis were present in 11 patients and cerebellar dysfunction in 9 patients. In 4 cases, CT showed widening of the brain stem with disappearance of the surrounding cisterns. The cerebrospinal fluid was abnormal in all patients in whom this investigation was done (pleocytosis, elevation in protein content). The patients received antibiotic therapy for 2-6 weeks. In the 9 patients who recovered, the neurological dysfunction improved within 2 days to 1 week of the initiation of therapy. There were 5 deaths. At autopsy in 2 cases, there was severe purulent meningitis and rhombencephalitis with predominantly polymorphonuclear cellular infiltration in 1 case, while numerous microabscesses in the midbrain, pons and medulla were observed in the other. We conclude that L. monocytogenes infection should be considered in patients who develop fever and focal neurological signs particularly localized to the brain stem. PMID- 8496713 TI - Preserved cortical somatosensory evoked potentials in apnoeic coma with loss of brain-stem reflexes: case report. AB - A comatose patient suffering from diffuse cerebellar haemorrhage developed apnoea and brainstem areflexia, i.e. the clinical signs of brain death. However, median nerve somatosensory evoked potential testing 2.5 h and 22 h after the onset of this clinical syndrome showed cortical potentials partly preserved; these were abolished 46 h after the beginning of the clinical signs of brain death. This case report underlines the need for electrophysiological confirmation of brain death in patients with primarily infratentorial lesions. PMID- 8496714 TI - Nocturnal sleep in multisystem atrophy with autonomic failure: polygraphic findings in ten patients. PMID- 8496715 TI - Central nervous system involvement in Leber's optic neuropathy. AB - Six months after the onset of visual loss a 23-year-old male patient with Leber's optic neuropathy associated with a mitochondrial DNA mutation developed brain stem involvement with Parinaud's syndrome and oculopalatal myoclonus. Magnetic resonance imaging (MRI) revealed a high signal area in the brain stem, corresponding to a hypodense area in the CT scan that did not show contrast enhancement. Distinct diminution but not complete remission of the MRI findings was found in the 5-year follow-up, which was not accompanied by clinical improvement. Although the MRI findings were compatible with a demyelinating lesion, neither extensive evoked potential studies nor spinal fluid examination supported this. PMID- 8496716 TI - Evidence of a genetic marker associated with early onset in Friedreich's ataxia. AB - We evaluated the association between age at onset of Friedreich's ataxia and alleles of two restriction fragment length polymorphisms (RFLP) at D9S15 and D9S5 in the 9q13-9q21.1 region. We studied 65 Italian patients from 49 families. Age at onset was not normally distributed in our patients, suggesting allelic heterogeneity. Patients homozygous for allele 1 of MspI RFLP detected by probe MCT112 at D9S15 (M1) had an earlier onset (mean 9.3, SD 3.4 years) than patients homozygous for allele 2 (M2; mean 12.1, SD 4.3). Heterozygotes had an onset age similar to that of the M2 homozygotes. These findings suggest that the M1 allele might be a marker of one allelic early-onset Friedreich's ataxia mutation. PMID- 8496717 TI - Basal ganglia involvement in multiple sclerosis with alternating side paroxysmal dystonia. PMID- 8496718 TI - Tetraparetic mutism. PMID- 8496719 TI - Lumbosacral polyradiculopathy associated with HIV infection. PMID- 8496720 TI - Cardiovascular risk factors in young children. PMID- 8496721 TI - Physical and mental health relationships in the very old. AB - A descriptive, correlational study was conducted to examine the physical and mental health status of 80-year-olds. Thirty-seven community-dwelling adults, aged 80 and over, were interviewed about their physical health, psychological well-being, and demographic characteristics. Both descriptive and correlational data indicated that overall these older adults were positive about both their physical health and psychological well-being. However, depression emerged as a significant problem for 24% of the sample and was strongly related to physical health problems. Results are discussed in relation to both health needs and stereotypic beliefs about the very old. PMID- 8496722 TI - Wound management in home care: an assessment. AB - The purpose of this study was to determine the status of wound care management among home health agencies (HHAs) in the U.S. The survey was mailed to 562 randomly selected HHAs within all 10 HCFA regions. Two hundred and ninety-six agencies (53%) responded to the survey. The majority (56%) of the respondents did not have written policies and procedures specific to wound management. The investigators were able to analyze the documents of those who had indicated that they had written policies and sent copies of them (n = 87, 67%). The majority (76%) of these had separate wound assessment protocols, but only 14% had separate preventive skin assessment protocols. Sixty-four percent had treatment protocols for more than one type of wound, while the remaining 46% used no specific treatment protocol or used treatments based on physicians' orders only. Most of the HHAs with written wound management policies required documentation of wound status; however, only half had patient/caregiver teaching as part of the policy. Although there is a need for clinically useful, well-tested, standardized approaches to wound care, the results of this study indicated that there is inconsistency regarding wound care management among HHAs within the U.S. PMID- 8496723 TI - Progressive relaxation and the sleep of older men and women. PMID- 8496724 TI - Home health care services for AIDS patients: one community's response. AB - The AIDS epidemic has challenged communities to develop and mobilize care networks for persons infected with the human immunodeficiency virus (HIV). A major part of that mobilization has been a push toward community- and home-based services. The movement of HIV care to the home/community setting is occurring, however, without investigation of either the problems that this change engenders for agencies providing care or the agencies' responses to these problems. This article from one health care market suggests that home care agencies may not be well positioned to meet the cyclical needs of HIV patients, that care is becoming increasingly fragmented with multiple agencies seeking to patch together a program of comprehensive services, and that agency policies may be limiting the numbers of community-based HIV patients eligible for home care. PMID- 8496725 TI - Family as client: using Gordon's health pattern typology. AB - The community health nursing faculty at Kent State University organized a family assessment instrument in accordance with the health pattern typology described by Gordon (1982). Students use the instrument with traditional and nontraditional families at every stage of the family life cycle. Reasons for initial visits to the families range from newborn health promotion to skilled nursing for acute and chronic conditions. The instrument helps students conceptualize the family as client and explore the concept of family nursing diagnoses. PMID- 8496726 TI - Image recovery from data acquired with a charge-coupled-device camera. AB - A model for data acquired with the use of a charge-coupled-device camera is given and is then used for developing a new iterative method for restoring intensities of objects observed with such a camera. The model includes the effects of point spread, photoconversion noise, readout noise, nonuniform flat-field response, nonuniform spectral response, and extraneous charge carriers resulting from bias, dark current, and both internal and external background radiation. An iterative algorithm is identified that produces a sequence of estimates converging toward a constrained maximum-likelihood estimate of the intensity distribution of an imaged object. An example is given for restoring images from data acquired with the use of the Hubble Space Telescope. PMID- 8496727 TI - Maximum a posteriori estimation with Good's roughness for three-dimensional optical-sectioning microscopy. AB - The three-dimensional image-reconstruction problem solved here for optical sectioning microscopy is to estimate the fluorescence intensity lambda(x), where x epsilon R3, given a series of Poisson counting process measurements [Mj(dx)]jJ = 1, each with intensity [formula: see text] with [formula: see text] being the point spread of the optics focused to the jth plane and sj(y) the detection probability for detector point y at focal depth j. A maximum a posteriori reconstruction generated by inducing a prior distribution on the space of images via Good's three-dimensional rotationally invariant roughness penalty [formula: see text] It is proven that the sequence of iterates that is generated by using the expectation maximization algorithm is monotonically increasing in posterior probability, with stable points of the iteration satisfying the necessary maximizer conditions of the maximum a posteriori solution. The algorithms were implemented on the DECmpp-SX, a 64 x 64 parallel processor, running at < 2 s/(64(3), 3-D iteration). Results are demonstrated from simulated as well as amoebae and volvox data. We study performance comparisons of the algorithms for the missing-data problems corresponding to fast data collection for rapid motion studies in which every other focal plane is removed and for imaging with limited detector areas and efficiency. PMID- 8496728 TI - Undetected gray strips displace perceived edges nonlinearly. AB - The luminance profile of a contour affects its perceived location. We measured the relationship between luminance profile and perceived location of an edge by interposing a thin uniform strip of variable luminance between the black and the white sides of a sharp edge and having observers make Vernier adjustments of an uncomplicated sharp edge so that the two edges appeared to be aligned. The perceived location of the contour depended on the luminance of the strip even when the strip itself was too thin to be seen. The largest visual angle at which a strip was still invisible was approximately 1.4'. Although the relation between perceived location and luminance was nonlinear, the relation approached linearity as the strip thickness decreased. A model with no free parameters, involving three stages of spatial filtering and an interposed nonlinearity, described the data from strips that could not be seen. With a strip thickness of 1.4', the model halved both errors of prediction and residual variance over those based on the assumption of linearity. PMID- 8496729 TI - Achromatic and chromatic sensation as a function of color temperature and retinal illuminance. AB - Changes in color appearance with retinal illuminance were studied by scaling the achromatic, yellow, and blue sensation components for test lights with color temperatures from 3041 to 8650 K at 4.10, 2.18, and 0.33 log Td. At 4.10 log Td two observers showed similar pure whites (4823 and 5258 K) and narrow transition zones (1502 and 969 K) from yellow to blue chromatic response categories. The relative amounts of yellow, blue, and white varied with color temperature in a similar manner for both observers. One observer maintained similar absolute whites and transition zones for all illuminances. For the second observer the transition zone broadened and shifted to higher color temperatures as illuminance decreased. At color temperatures both above and below the transition zone chromatic saturation was greatest at the intermediate illuminance. The loss of saturation at 0.33 and 4.10 log Td is consistent with the observation that as the illuminance of a spectral color is raised above threshold, saturation increases to a maximum and then falls. Our findings reinforce the notion that at relatively low illuminances chromatic responses increase with increasing illuminance more rapidly than achromatic responses and that the opposite is true at high illuminances. PMID- 8496730 TI - Effect of some properties of metal strengtheners on the fracture resistance of acrylic denture base material construction. AB - In this study we investigated the effect of metal wire bonding to acrylic resin on the fracture resistance of an acrylic denture base material construction. Two different bonding methods were tested, and after measuring the resistance, the surface of the wires were examined by a scanning electron microscope. The effect that the placing of metal strengtheners in different positions in the acrylic resin had on the fracture resistance of the denture base material construction was also clarified. When three different positions of the metal wires in the acrylic resin were compared, the results showed that bonding of metal wire to acrylic resin somewhat enhanced the fracture resistance of test specimens, while the different positions of the wires had no effect on the fracture resistance. PMID- 8496731 TI - The use of intermediary resins when bonding glass polyalkenoate (ionomer) cement to composite resin. AB - This study was designed to examine the effects of three different types of glass polyalkenoate lining cement combined with three different types of bonding resin and varying surface treatments on the seal between the lining cement and the composite resin as used in the so called 'laminate' technique. The seal was assessed using a radioisotope and autoradiographic technique. Results showed that all the cements behaved in a manner specific to them. The seal of all systems examined could be improved, or at least, not compromised, by modification of the surface of the cement prior to attachment of the resin. Only one type of intermediate resin gave a reliable seal when applied to an unmodified surface of any of the cements under investigation. It is concluded that all the glass polyalkenoate cements tested behave differently when used beneath composite resin. Recommendations about the laminate restoration technique must be related to the specific combinations of materials used. PMID- 8496732 TI - Comparison of the marginal and axial wall integrity of in vivo and in vitro made adhesive class V restorations. AB - For several different procedures and material combinations adhesive Class V composite restorations were made under clinical and under laboratory conditions. Marginal discrepancy and gap formation at the floor of the cavity was recorded by way of SEM on replicas. Only weak correlation could be demonstrated between results obtained from in vivo and in vitro placed restorations. In general the hydrophobic resinous bonding systems performed better under laboratory conditions while the hydrophilic glass ionomer lining led to a better marginal integrity under clinical circumstances. PMID- 8496733 TI - Electromyographic activity of human masticatory muscles in normal young people. Statistical evaluation of reference values for clinical applications. AB - Electromyographic activity of anterior temporal and masseter muscles was measured in 92 young healthy men and women with sound dentitions during rest position, contact in centric occlusion and clench. Male and female mean potentials were similar except in clench, where males had higher electromyographic levels. Mean pooled electromyographic potentials were 1.9 microV (TA) and 1.4 microV (MM) during rest position, 6.5 microV (TA) and 2.8 microV (MM) during contact in centric occlusion. Mean maximum voluntary clench potentials were 181.9 microV (TA) and 216.2 microV (MM) in men, 161.7 microV (TA) and 156.8 microV (MM) in women. Examined muscles were more asymmetric at low electromyographic activity (rest and centric occlusion) with the temporal muscle less asymmetrical than the masseter. In females temporal muscle activity tended to dominate at every contraction level, while in males masseter activity was stronger in clench, and temporal activity in centric occlusion and in rest position. PMID- 8496734 TI - Contribution of periodontal receptors and food qualities to masseter muscle inhibition in man. AB - Previous studies of human muscle inhibition during chewing have shown that many factors contribute to the incidence and intensity of this reflex but few studies have been in a physiological context. During the first crushing cycle of brittle foods ipsilateral masseter muscle EMG, mandibular movement and vibration were recorded simultaneously in four healthy dentate subjects. Experiments were repeated before and during anaesthesia of the cheek teeth on the chewing side. The results suggest that vibration seems to be the most important factor in muscle inhibition during food crushing; conversely periodontal sensation, mandibular closing movement and the preload by the muscle at the onset of food fracture play a minor role. PMID- 8496735 TI - An investigation into the quality of dentine bonding systems for accomplishing a durable bond. AB - For a wide variety of dentine bonding systems the bond strength before and after thermocycling was determined on dentine with and without hydraulic tubular pressure. The importance of the hydrophilic nature of several bonding systems could be demonstrated. The dentine smear layer could not prevent a negative effect of water in the tubulus on hydrophobic systems. Removal of the smear layer had a positive effect on the durability of the bond. When loaded until fracture, some bonding systems resisted adhesive failure. PMID- 8496736 TI - Relationship between mean power frequency and potential of human masticatory muscles at rest position and clenching. AB - The EMG signals from left and right masseter and anterior temporal muscles of 40 healthy subjects were sampled at rest position and through gradually increased clench level to maximum voluntary contraction (MVC) at intercuspal position. A visual sense feedback of masseter muscle potential value was used for the subject to control clench level. The relationship between mean power frequency (MPF) and potential of EMG was investigated by a curvilinear regression of the second order. It was found that the relationship was of the second order logarithmic curve with maximum value of MPF. With the raising of the potential levels of EMG, the MPF increased at the lower clench levels and decreased at higher clench levels. The results indicate that controlling an identical clench level is necessary for using MPF to describe the functional state of masticatory muscles in the clinical situation. PMID- 8496737 TI - The release of chlorhexidine from modified dental acrylic resin. AB - A method for the incorporation of chlorhexidine into acrylic resin using monomer together with the pattern of release of chlorhexidine from treated resin into water at 37 degrees C is described. Release from polished and unpolished resin, and from acrylic prepared by short-curing and dry-curing processes are investigated. The pattern of release in all cases was of an exponential nature, showing a rapid release within the first 10 days becoming almost constant at a level of 0.4-1.5 micrograms cm-2 at about 20 days. Release was still evident at the end of the test period in all cases. Release of chlorhexidine into water from the short-cure specimens was accompanied by release of monomer, evident from the odour of the test solutions, indicating that polymerization was not complete. PMID- 8496738 TI - Fatigue and EMG changes in the masseter and temporalis muscles during sustained contractions. AB - Local muscle fatigue was investigated in the anterior temporal and masseter muscles during sustained isometric contractions. The volunteers' subjective perception of fatigue or pain was recorded at intervals during the sustained contractions, and this level was then compared to objective measures of fatigue. These objective measures included shift in median frequency of the power spectrum of the surface-detected EMG signal, and change in signal amplitude. The relationship was investigated while closing on a bite force meter placed between the second premolars and first molars unilaterally, and while simply clenching with the teeth together without the bite force meter. It was found that the subjective perception of fatigue, as measured on a visual analogue scale (VAS), had a nearly linear relationship with time, and that the relationship between the VAS score and median frequency shift was rather closer than the relationship with amplitude change. PMID- 8496739 TI - Nature and frequency of dental wear facets in an Australian aboriginal population. AB - The nature and frequency of dental wear facets were studied in a sample of 18 year-old Aborigines, 28 males and 31 females, living at Yuendumu in the Northern Territory of Australia. Facet frequencies were scored indirectly using dental models for all permanent teeth, except third molars, and evidence of non masticatory tooth grinding in eccentric jaw positions was also recorded. The interplay between attrition and abrasion in an individual over time was assessed by examining facet appearance on serial dental models obtained at approximately yearly intervals from 7 to 25 years of age. Facetting was found to be a very common feature of the Aboriginal dentitions, with frequencies ranging from around 65% for pre-molars to about 90% for molars. Evidence of extreme mandibular movement was noted in 93% of males and 100% of females. The longitudinal observations indicated that wear facet definition varied over time, apparently due to episodes of tooth grinding superimposed on continually-acting abrasive influences. These results show that facetting on teeth associated with extreme mandibular positions and, by inference, the related behaviour of tooth grinding or bruxism are very common features in dentitions of Australian Aboriginals living an essentially non-industrial way of life. PMID- 8496740 TI - Longitudinal study on torque transmitted from denture base to an abutment tooth of lower distal-extension removable partial dentures with conus crown telescopic system. AB - The purpose of this study was to make a longitudinal analysis of torque transmitted to a direct abutment tooth of a lower distal-extension removable partial dentures constructed with the conus crown telescopic system. Torque around the vertical and lateral axes of the tooth were measured during chewing of food at the time of insertion of the new dentures to about three months after. The maximal mean value of torque (Max.MT) was calculated from the peak level of all chewing strokes at the minimum of the interocclusal distance. The integration values of torque (I) and time (T) from initiation of chewing to swallowing were obtained, then the average value of torque (Ave.T) was calculated (Ave.T = I/T). The results are summarized as follows: (a) There were no remarkable changes of Max.MT around the both axes; (b) Max.MT around the lateral axis was 7-47 x 10(-3) kgm (mean: 25 x 10(-3) kgm) (1 kgm = 9.8 Nm) in the downward direction and Ave.T around the lateral axis was 6-14 x 10(-3) kgm ss-1 (mean: 10 x 10(-3) kgm ss-1) in the downward direction; (c) There were marked differences of Max.MT and Ave.T around the vertical axis between subjects. Max.MT around the vertical axis was less than 24 x 10(-3) kgm and Ave.T around the vertical axis was less than 6 x 10(-3) kgm ss-1. PMID- 8496741 TI - [94th annual meeting of the Oto-Rhino-Laryngological Society of Japan. Kyoto. Japan. May 27-29, 1993]. PMID- 8496742 TI - Alternating hemiplegia of childhood. AB - We report 22 cases of alternating hemiplegia of childhood. In addition to repeated episodes of hemiplegia lasting from a few minutes to several days, the disease was characterized by an onset before 18 months of age, the occurrence of tonic or dystonic attacks, nystagmus, dyspnea and other autonomic phenomena, and the development of cognitive impairment and of a choreoathetotic movement disorder. All the patients also had episodes of quadriplegia that occurred either when a hemiplegia was shifting from one side to the other or as an isolated manifestation. Such episodes were often severe and followed by developmental deterioration. In all children, sleep consistently relieved both weakness and associated paroxysmal phenomena, but these would reappear 10 to 20 minutes after the children awakened, during long-lasting episodes. Although six patients also had epileptic seizures, the condition seems to be distinct from epilepsy, and the clinical features and poor outcome differentiate it from migraine. Treatment with the calcium-entry blocker flunarizine was partially effective. PMID- 8496743 TI - Clinical diagnoses of children with extremely short stature and their response to growth hormone. AB - This study was undertaken to determine the prevalence of clinical diagnoses in a group of children with extremely short stature (standard deviation score for height, < -2.5) and to determine whether the classification might help in predicting response to human growth hormone (hGH) treatment. We classified 49 children referred consecutively to our outpatient clinic for evaluation of short stature with heights < -2.5 standard deviation score and bone ages < 9 years for girls or < 10 years for boys (to avoid an effect of puberty on the response to hGH). The diagnostic categories were growth hormone (GH) deficiency, constitutional delay, familial short stature, and primordial short stature. After referral, Turner syndrome was diagnosed in two children. The remaining 47 children were classified according to primary criteria, considered essential for the diagnosis, and secondary criteria, considered necessary but of lesser importance. There were five children, four children, no children, and one child classified, respectively, with GH deficiency, constitutional delay, familial short stature, and primordial short stature by using the most rigorous definitions of the diagnoses. There was significant overlap in the diagnoses other than GH deficiency. Growth hormone deficiency defined by the primary criterion of peak stimulated GH values < 5 micrograms/L was the most definitive. Of the 47 children, 7 were classified as GH deficient by this criterion and 5 were classified as GH deficient by the primary and secondary criteria. The mean pretreatment growth rate (3.1 +/- 1.9 cm/yr) of the group with stimulated GH values < 5 micrograms/L was significantly less than that in the other groups (4.2 +/- 1.5 cm/yr). The mean growth rate of the children with GH deficiency during treatment with hGH was greater than that in the other groups and was 3.4 times greater than the pretreatment growth rate. The mean growth rate of children in the other groups during hGH treatment was twofold greater than the pretreatment growth rate. We conclude that except for GH deficiency, children with an extreme degree of short stature are not easily classified by standard diagnostic criteria, and that most short children have a positive response to hGH therapy regardless of the diagnosis; therefore a specific clinical diagnosis should not be used to exclude children from hGH therapy. PMID- 8496744 TI - Repair of osteopenia in children with juvenile rheumatoid arthritis. AB - To test the hypothesis that the presence of osteopenia in juvenile rheumatoid arthritis is directly correlated with clinical disease activity and therefore reversible, we prospectively studied cortical bone mineral density (BMD) serially in 27 children. Twenty-four (89%) had BMD > or = 2 SD below age-related normal values (disease duration 49.3 +/- 7.7 months) at the beginning of the study. Of 27 children who had clinical disease improvement measured by a disease activity score during our study period, 17 (63%) had significant improvement or significant normalization, or both, of their BMD (0.34 +/- 0.13 gm/cm2 at initiation and 0.41 +/- 0.17 gm/cm2 at completion, p < 0.05; disease activity score of 3.4 +/- 0.2 at initiation and 1.4 +/- 0.2 at completion, p < 0.005). The increase in BMD was associated with a similar directional change in serum osteocalcin concentrations (4.6 +/- 1 ng/ml at initiation vs 9.1 +/- 1.1 ng/ml). The 10 patients whose disease became or remained active had a decreased or unchanged low serum osteocalcin level and BMD (BMD 0.37 +/- 0.17 gm/cm2 at initiation and 0.37 +/- 0.16 gm/cm2 at completion; disease activity score of 3.1 +/- 0.3 at initiation and 3.4 +/- 0.2 at study completion). We conclude that children with JRA who have improvement in their disease activity have an improvement in BMD heralded by an increase in serum osteocalcin values. PMID- 8496745 TI - Safety and immunogenicity of bacille Calmette-Guerin, diphtheria-tetanus pertussis, and oral polio vaccines in newborn children in Zaire infected with human immunodeficiency virus type 1. AB - OBJECTIVE: To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Nonrandomized, prospective cohort study; 12-month follow-up period. SETTING: Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire. PATIENTS: A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated. INTERVENTION: The following vaccines were administered at the stated ages: bacille Calmette-Guerin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks). MEASUREMENTS AND MAIN RESULTS: Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children. CONCLUSIONS: The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas. PMID- 8496746 TI - Carotenoid levels in normal children and in children with cystic fibrosis. AB - The carotenoids are potent antioxidants with the ability to quench singlet oxygen and other toxic oxygen species. We studied 17 patients with cystic fibrosis (CF) and 10 normal children to assess plasma levels of four carotenoids, beta carotene, alpha-carotene, lutein, and lycopene, by high-performance liquid chromatography. We found significantly lower plasma levels of specific carotenoids in children with CF than in normal control subjects. The standardization of carotenoid levels for total cholesterol did not significantly attenuate these differences. No differences in total carotene intake were apparent between the groups. Carotenoid levels did not correlate with fat absorption or measures of adiposity in children with CF. Additionally, levels of selected carotenoids correlated negatively with serum IgG levels, an indirect measure of inflammation. The differences in plasma carotenoid levels between children with CF and normal children may be due to rapid turnover of carotenoids, perhaps through quenching of toxic oxygen species in inflammatory states of CF. Studies assessing supplementation of these antioxidants should be considered. PMID- 8496747 TI - Detection of inborn errors of fatty acid oxidation from acylcarnitine analysis of plasma and blood spots with the radioisotopic exchange-high-performance liquid chromatographic method. AB - Sixty-one plasma samples from patients with inborn errors of fatty acid oxidation and from control subjects were analyzed in a blinded fashion for acylcarnitines by the radioisotopic exchange-high-performance liquid chromatographic method. All samples from patients with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency (n = 30), some of which had been stored in a frozen state for several years, showed a prominent octanoylcarnitine peak. In all blood spots from 11 patients with MCAD deficiency, octanoylcarnitine was also detected. Control plasma specimens and blood spots contained small amounts of octanoylcarnitine; however, the octanoylcarnitine/acetylcarnitine ratio differentiated patients with MCAD deficiency. Longer-chain acylcarnitines were found in plasma of all three patients with defects in long-chain fatty acid oxidation. Plasma and blood spots from a patient with multiple acyl-coenzyme A dehydrogenase deficiency contained C4-acylcarnitine, hexanoylcarnitine, octanoylcarnitine, and decanoylcarnitine. The results suggest that the method may be highly sensitive in detecting MCAD deficiency and other defects in fatty acid oxidation from plasma or blood spots. PMID- 8496748 TI - Prevalence of medium-chain acyl-coenzyme A dehydrogenase deficiency in the sudden infant death syndrome. AB - Disorders of fatty acid beta-oxidation have been suggested as playing a significant role in the sudden infant death syndrome (SIDS). To elucidate the role of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in SIDS, we identified all cases of SIDS occurring in Los Angeles County between January 1986 through December 1991. A total of 1304 SIDS deaths were identified; tissue samples were collected in 1236 cases (94.8%). Extraction of DNA was successful in 1224 tissue samples (93.9%), which were examined for the presence of the G985 mutation, identified as occurring in more than 88% of affected cases of MCAD deficiency. Three heterozygotes and no homozygotes were identified; this incidence does not differ from that reported in the general population. Review of the pathologic specimens from the identified heterozygotes and from 18 ethnic-, age-, and sex-matched control subjects revealed significant fatty infiltration of all organs examined in one of the three heterozygotes and in none of the control subjects. We conclude that MCAD deficiency does not play a significant role in the causation of SIDS. PMID- 8496749 TI - Elevated lead levels in reportedly abused children. AB - Children suspected of having been physically abused had significantly higher venous blood lead levels than a comparison group (p < 0.0001). Abused children were 27-fold more likely to have lead levels > 0.965 mumol/L (20 micrograms/dl) (odds ratio = 26.7). We recommend that abused children be monitored for lead intoxication more frequently than other children. PMID- 8496750 TI - Increased very long chain fatty acids in patients on a ketogenic diet: a cause of diagnostic confusion. AB - We found an elevation of very long chain fatty acids in 13 of 22 plasma samples from patients on a ketogenic diet for the treatment of uncontrolled seizures. Because elevated values of very long chain fatty acids are a biochemical manifestation of peroxisomal dysfunction, this phenomenon might lead to diagnostic confusion. Thus the history and clinical status should be considered when plasma levels of very long chain fatty acids are interpreted. PMID- 8496751 TI - T cell activation and cytokine release in streptococcal toxic shock-like syndrome. AB - A 5-year-old girl with streptococcal toxic shock-like syndrome during varicella infection had high levels of tumor necrosis factor alpha and interleukin-6 but no interleukin-1 or interleukin-2 in the serum. Intravenous administration of gamma globulin coincided with clinical improvement and with reduction of the levels of tumor necrosis factor alpha and interleukin-6. The data suggest that streptococcal pyrogenic exotoxins trigger synthesis of tumor necrosis factor alpha and interleukin-6 in vivo; intravenously administered gamma-globulin may down-regulate the cytokine response. PMID- 8496752 TI - Solitary rectal ulcer syndrome in a child. AB - We describe a 6-year-old boy with solitary rectal ulcer syndrome, and the sigmoidoscopic and histopathologic findings. The evolution of the histologic features and the absence of trauma suggest that the origin of the ulceration is ischemic in nature. PMID- 8496753 TI - Long-term evolution of chronic delta hepatitis in children. AB - Twenty-three children, aged 3 to 15 years, with chronic delta hepatitis have been followed for 5 to 12 years to evaluate long-term outcome. Although 83% of patients had chronic active hepatitis when first seen, with cirrhosis in 26%, the clinical and biochemical features of the disease remained reasonably stable during observation; liver histologic findings, obtained in 14 patients, worsened in only two. PMID- 8496754 TI - Selenium status of term infants fed human milk or selenite-supplemented soy formula. AB - Infants fed a soy formula supplemented with selenite had plasma and erythrocyte selenium values lower than those of infants fed human milk. However, plasma and erythrocyte glutathione peroxidase activities were normal, indicating that the physiologic requirement for selenium was being met. PMID- 8496755 TI - Treatment of persistent pulmonary hypertension in the newborn lamb by inhaled nitric oxide. AB - We previously showed that fetal lambs whose ductus arteriosus is ligated prenatally will have persistent pulmonary hypertension at birth. We investigated the effect of inhaled nitric oxide on the pulmonary circulation in this animal model. The ductus arteriosus of six fetal lambs was ligated at 126 days of gestation. The lambs were delivered and studied at 136 days of gestation. Mechanical ventilation was maintained at a fraction of inspired oxygen of 0.80. Nitric oxide gas was administered at five different concentrations (6, 12, 25, 50, and 100 ppm) for 5-minute periods separated by 10-minute periods of ventilation without nitric oxide. Inhaled nitric oxide caused dose-dependent decreases in pulmonary arterial pressure and vascular resistance and dose dependent increases in pulmonary blood flow without affecting systemic arterial pressure. Thus pulmonary arterial pressure decreased from equal to aortic pressure to less than aortic pressure. At the highest dose, mean pulmonary arterial pressure decreased by 27% +/- 2%, pulmonary blood flow increased by 86% +/- 6%, and pulmonary vascular resistance decreased by 59% +/- 4%. Nitric oxide also caused dose-dependent increases in systemic arterial oxygen tension and in the saturation of hemoglobin with oxygen. Partial pressure of arterial oxygen increased from 43 +/- 16 mm Hg at baseline to 185 +/- 72 mm Hg at the highest dose; saturation increased from 74% +/- 8% to 96% +/- 2%. In our model of persistent pulmonary hypertension of the newborn, inhaled nitric oxide selectively dilates the pulmonary circulation, thereby improving systemic arterial oxygenation. Nitric oxide is a promising new treatment of persistent pulmonary hypertension of the newborn. PMID- 8496756 TI - Effect of enteral gavage feeding rate on pulmonary functions of very low birth weight infants. AB - To compare the effects of intermittent and continuous feedings on pulmonary function, we studied 24 very low birth weight neonates (mean +/- SD: birth weight, 1.2 +/- 0.3 kg; gestational age, 30.5 +/- 1.1 weeks) at 2 to 4 weeks of age. All infants had a previous diagnosis of respiratory distress syndrome but no subsequent diagnosis of bronchopulmonary dysplasia. Pulmonary mechanics were measured before the beginning of intermittent or continuous feedings and 10 minutes after each meal was completed. Twelve infants were randomly assigned to intermittent and 12 to continuous feedings. These infants had similar birth weight, gestational age, study age, and baseline lung function. After intermittent feedings, there was a significant decrease in tidal volume (38%), minute ventilation (44%), and dynamic compliance (28%), whereas pulmonary resistance increased significantly (100%). In comparison, the pulmonary function data remained unchanged after continuous feedings. These data demonstrate that intermittent feeding of very low birth weight infants can lead to airflow and respiratory instability. These adverse effects appear to be dependent on the rate that feedings are administered. A slower pace of feeding may be more advantageous for infants prone to respiratory instability. PMID- 8496757 TI - Ureaplasma urealyticum infection associated with acute respiratory insufficiency and death in premature infants. AB - The incidence and outcome of Ureaplasma urealyticum infection were studied in 98 infants born before 34 weeks of gestational age. Infection was defined as the presence of one or more isolations of U. urealyticum in samples obtained from trachea, blood, cerebrospinal fluid, or postmortem brain or lung biopsies. Forty seven infants were infected. Intact amniotic membranes had no protective effect against infection; intrauterine U. urealyticum infection was detected in 19 infants who were born by cesarean section with intact amniotic membranes. Respiratory distress syndrome, the need for assisted ventilation, severe respiratory insufficiency, and death were significantly more common among infected than among noninfected infants. Our results suggest that U. urealyticum infection is associated with an unfavorable short-term outcome in preterm infants. PMID- 8496758 TI - Effect of parenteral calcium and phosphorus therapy on mineral retention and bone mineral content in very low birth weight infants. AB - HYPOTHESIS: If calcium and phosphorus are administered to very low birth weight infants in amounts larger than those currently used in standard parenteral nutrition solutions, apparent retention of calcium and phosphorus (intake minus urinary excretion) will increase and bone mineralization will improve. DESIGN: Randomized, controlled, double-blind trial. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-four very low birth weight infants (< 1.2 kg) expected to receive parenteral nutrition exclusively for approximately 3 weeks beginning 3 days after birth. INTERVENTIONS: Infants received parenteral nutrition solutions, either the standard mixture containing 1.25 mmol calcium and 1.5 mmol phosphorus per deciliter (group STAND: n = 12, birth weight 921 +/- 171 gm, gestational age 27 +/- 2 weeks (mean +/- SD)) or 1.7 mmol calcium and 2.0 mmol phosphorus per deciliter (group HIGH: n = 12, 857 +/- 180 gm, 27 +/- 2 weeks). MAIN OUTCOME MEASURES: Intake, urinary excretion, and apparent retention of calcium, phosphorus, and magnesium every 3 days during parenteral nutrition therapy. Serum indexes of mineral status twice during therapy. Bone mineral content of the distal segment of the left radius at 1, 4, 8, and 26 weeks. RESULTS: Apparent calcium retention (1.2 +/- 0.2 vs 1.6 +/- 0.2 mmol.kg-1.d-1) and phosphorus retention (1.4 +/- 0.2 vs 1.8 +/- 0.4 mmol.kg-1.d-1) differed significantly (p < 0.01) between groups STAND and HIGH, respectively; neither changed with the duration of parenteral nutrition therapy. Serum calcium, magnesium, parathyroid hormone, 25-hydroxyvitamin D, and osteocalcin concentrations were similar in both groups. Serum phosphorus concentration was significantly higher in group HIGH than in group STAND (p = 0.025). The absolute bone mineral content and the rate of increase in bone mineral content between 1 and 4, 1 and 8, and 1 and 26 weeks were significantly greater in group HIGH than in group STAND. CONCLUSIONS: Increased parenteral intakes of calcium and phosphorus resulted in greater retention of these minerals during parenteral nutrition therapy and in greater bone mineral content after therapy. PMID- 8496759 TI - Comparison of temperature measurements by an aural infrared thermometer with measurements by traditional rectal and axillary techniques. AB - OBJECTIVE: To compare temperatures obtained with glass-mercury axillary and aural infrared thermometers with temperatures obtained with glass-mercury rectal thermometers. DESIGN: Blind comparison with criterion standard. SETTING: Well baby nursery at a private teaching hospital. PATIENTS: Convenience sampling of 200 term newborn infants. INTERVENTION: Temperatures were measured simultaneously with glass-mercury rectal and axillary thermometers for a 3-minute period by one investigator. In a blinded fashion, a second investigator obtained three aural temperatures by using two tympanic membrane thermometers. One tympanic membrane reported infants' rectal-equivalent temperatures, and a second reported oral equivalent temperatures. RESULTS: Temperatures obtained with glass-mercury rectal and axillary thermometers for the population were similar (37 degrees +/- 0.4 degree C vs 36.8 degrees +/- 0.3 degrees C, respectively), but 25% of measurements at these two sites differed by > 0.3 degree C. Oral-equivalent tympanic membrane temperatures were more accurate than rectal-equivalent temperatures in predicting an infant's glass-mercury axillary and rectal temperatures (75% of oral-equivalent temperatures vs fewer than 50% of rectal equivalent temperatures were within 0.3 degree C of either glass-mercury rectal or axillary measurements). CONCLUSIONS: Temperatures obtained with glass-mercury axillary and rectal thermometers are similar in most cases. However, temperatures obtained with tympanic membrane thermometers either in the rectal-equivalent mode or in the oral-equivalent mode did not accurately reflect an infant's rectal or axillary temperature. We believe that tympanic membrane temperatures should not be substituted for rectal or axillary temperatures in assessments of newborn infants. PMID- 8496760 TI - Hyperimmune human IgG or recombinant human granulocyte-macrophage colony stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats. AB - Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis. PMID- 8496761 TI - Immunoglobulin secretion by the normal and the infected newborn infant. AB - The development of quantitative single-cell immunoassays has provided a novel opportunity to demonstrate the isotype-specific immunoglobulin responses in normal and infected neonates. The reverse enzyme-linked immunospot assay was used to determine the number of immunoglobulin-secreting cells (IgSCs) in peripheral blood. Baseline numbers of IgSCs were established in 69 uninfected term and preterm infants within 5 days of birth; values above the 99th percentile were considered elevated. The IgSCs were also measured in 266 infants with proved or suspected infections or congenital anomalies. A subset of newborn infants was retested weekly. Few IgSCs (mostly IgMSCs) were detected within 5 days of birth in uninfected neonates, but by 1 month 77% had increased numbers of IgSCs, primarily IgASCs. Sixty-three (24%) of 266 study infants had increased IgSCs on initial sampling (predominantly IgMSCs); these included infants as immature as 25 to 27 weeks of gestational age; elevations in IgSCs were most frequent in infants with intrauterine infections. Increased numbers of IgSCs were uncommon in infants with early-onset sepsis in the first 5 days but were frequent by the second week, consistent with acquisition of infection near the time of delivery. We conclude that the presence of elevated numbers of IgSCs soon after birth may be a useful surrogate marker of untreated intrauterine infection. The development of predominantly IgASCs in the first month of life suggests postnatal exposure to common mucosal antigens. PMID- 8496762 TI - Respiratory syncytial virus-specific immunoglobulins in preterm infants. AB - Incomplete transfer of maternal antibodies specific to respiratory syncytial virus (RSV) has been suggested as an explanation for the increased risk of RSV infections in preterm infants. Antibodies directed against the two major RSV envelope glycoproteins, F and G, are protective in vitro and in vivo. Our study was conducted to measure IgG, IgG1, IgG2, and IgG3 antibody titers against the RSV F and G glycoproteins in cord sera from infants born at different gestational ages. Titers of neutralizing antibody were measured in a subset of the subjects. The mean (+/- SEM) log2 titers of IgG antibodies directed against the RSV F and G glycoproteins were significantly lower in infants born at < or = 28 weeks of gestation (11.2 and 10.8 for F and G glycoproteins, respectively) than in term infants (12.6 and 12.8 for F and G, respectively) (p < 0.05). Preterm infants born at > or = 29 weeks had titers of antibodies against the F glycoprotein comparable to those of term infants. The highest titers of RSV-specific antibodies were in the IgG1 and IgG2 subclasses. Mean (+/- SEM) neutralizing antibody titers were lower in infants born at < or = 28 weeks (7.7 +/- 0.4) than in term infants (10.2 +/- 0.3) (p < 0.001). We conclude that (1) RSV-specific antibody titers were lower than in term infants only in the most premature infants (< or = 28 weeks) and (2) preterm infants born at > or = 29 or > or = 33 weeks of gestation had RSV-specific titers against F and G glycoproteins, respectively, that were comparable to those of term infants. Preterm infants born at < or = 28 weeks could represent a target population for passive immunoprophylaxis. PMID- 8496763 TI - Pneumocystis carinii pneumonia in a term newborn infant with a transiently depressed T lymphocyte count, primarily of cells carrying the CD4 antigen. AB - A term infant without infection by human immunodeficiency virus had pneumocystis pneumonia at 17 days of life. Initial counts of T lymphocytes carrying the CD4 antigen were approximately 50% of the lower limits of normal; later the counts of T lymphocytes carrying the CD3 and CD8 antigens decreased as well. By 7 weeks after resolution of the pneumonia, CD3+, CD4+ and CD8+ cell counts had returned to normal. These observations suggest that a primary transient deficiency of T cell production or maturation, especially involving CD4+ cells, may occur in otherwise normal newborn infants. PMID- 8496764 TI - Malposition of extracorporeal membrane oxygenation cannulas in patients with congenital diaphragmatic hernia. AB - We describe two infants with congenital diaphragmatic hernia who underwent extracorporeal membrane oxygenation and in whom the venous cannula was in the left atrium instead of the right. The routine radiograph of the chest failed to demonstrate the malposition. We recommend using the echocardiogram to confirm the position of the cannula or to guide the surgeon during the cannulation of patients with congenital diaphragmatic hernia. PMID- 8496765 TI - Efficacy of cough suppressants in children. AB - To test the hypothesis that codeine and dextromethorphan are effective in alleviating the symptoms of acute cough, we conducted a randomized, controlled trial. Eligible patients were children 18 months to 12 years of age, seen in private pediatric practices, with significant night cough of less than 14 days' duration. Study patients were randomly selected to receive codeine, dextromethorphan, or placebo at bedtime for 3 consecutive nights. Outcomes were assessed by the use of a parent questionnaire rating the severity of symptoms at the initiation of therapy, and after each night of the study. Every patient had a cough score (range 0 to 4) and composite symptom score (range 0 to 9) computed for each day of the study. One hundred forty-one doses of study medication were evaluated in 49 patients, including 13 children receiving placebo, 19 dextromethorphan, and 17 codeine. Mean cough and composite symptom scores decreased in each of the three treatment groups on each day of the study; there were no significant differences. Regression analysis, with reduction in cough score as the outcome of interest, showed that neither dextromethorphan nor codeine was significantly more effective than placebo (p = 0.41 and 0.70, respectively). Reduction in cough score was positively correlated with the severity of cough at the start of treatment (p = 0.007). Our data suggest that, in the doses used, neither codeine nor dextromethorphan is superior to placebo in treating night cough in children. PMID- 8496766 TI - Selective and sustained pulmonary vasodilation with inhalational nitric oxide therapy in a child with idiopathic pulmonary hypertension. AB - Low doses of inhaled nitric oxide caused selective and sustained pulmonary vasodilation in an infant with pulmonary hypertension without causing systemic hypotension, despite the failure of treatment with other vasodilators. PMID- 8496767 TI - Pharmacokinetics of dapsone in children. AB - We studied dapsone pharmacokinetics in eight children with compromised immune function who were receiving three different preparations. Peak serum concentration was less than 0.25 microgram/ml after doses of an extemporaneous liquid preparation but ranged from 0.72 to 1.33 micrograms/ml after initial tablet or proprietary liquid doses and 1.48 to 2.48 microgram/ml during long-term proprietary liquid administration. Elimination followed first-order kinetics; the mean elimination half-life was 15.1 hours. PMID- 8496768 TI - Correction of vitamin E deficiency with fat-soluble versus water-miscible preparations of vitamin E in patients with cystic fibrosis. AB - Of 27 patients with cystic fibrosis, 17 had levels of alpha-tocopherol more than 2 SD below the mean. Patients were randomly given either a water-miscible form of vitamin E or a fat-soluble form for 6 months. Either form was effective in achieving normal serum levels; the fat-soluble supplement has a significant cost advantage. PMID- 8496769 TI - Risks of human immunodeficiency virus infection among adolescents attending three diverse clinics. AB - This study was performed to identify specific high-risk behaviors, such as unprotected oral, anal, and vaginal intercourse and substance abuse, associated with human immunodeficiency virus infection among adolescents attending three diverse clinics located in a localized geographic area: a university-based clinic, a Planned Parenthood clinic, and an inner-city public health clinic (PHC). Six hundred seventy-one female and 207 male adolescents attending one of the three clinics completed a structured questionnaire. Similarities among patients at the clinic sites included high rates of anal intercourse (21%), unprotected vaginal sex (95%), oral sex (73%), and poor communication skills (42%). Some differences appeared as well, including higher rates of homosexual experiences, no birth control use, and having multiple partners among adolescents attending the PHC (p < 0.001). In contrast, adolescents attending either the university-based clinic or the Planned Parenthood Clinic had higher rates of substance abuse around sexual activity than those who attended the PHC (p < 0.001). We conclude that adolescents attending general medical clinics in the San Francisco Bay area engage in high-risk behaviors that place them at risk for transmission of human immunodeficiency virus even though many have had previous education about acquired immunodeficiency syndrome and sexually transmitted disease. Specific risk factors include unprotected receptive anal intercourse, unprotected vaginal intercourse with new and unknown partners, experience in homosexual behavior, high rates of oral sex, multiple partners, poor communication skills, and frequent use of illicit substances in conjunction with sex. The differences found among sites indicate the need for health care providers and prevention programs to provide emphasis on practices specific to the adolescents in their service area. PMID- 8496770 TI - Development of valve dysfunction in adolescents and young adults with Down syndrome and no known congenital heart disease. AB - We performed examinations and echocardiographic studies in 35 patients with Down syndrome (aged 20 +/- 4.2 years) with no known intracardiac disease. Sixteen patients (46%) had mitral valve prolapse; two of these also had tricuspid valve prolapse. Two had aortic regurgitation. Valve regurgitation was present in 4 (17%) of 23 patients more than 18 years of age but in none of the 12 patients 18 years of age or younger. We recommend screening of adolescent and young adult patients with Down syndrome for the development of valve dysfunction, especially before dental or surgical procedures. PMID- 8496771 TI - Helicobacter pylori infection in adolescents with eating disorders and dyspeptic symptoms. AB - The potential role of Helicobacter pylori infection of the antrum as a cause of symptoms of dyspepsia in patients with eating disorders was evaluated with an assay to detect H. pylori-specific IgG in serum. H. pylori-specific optical density readings were comparable for adolescents with eating disorders (0.133 +/- 0.063, mean +/- SD) and for two comparison groups, and were lower than readings for children with documented H. pylori infection. Symptoms referable to the gastrointestinal tract did not correlate with H. pylori status in the teenagers with eating disorders. PMID- 8496772 TI - L. Emmett Holt, Jr. PMID- 8496773 TI - Erythropoietin treatment and blood transfusions in preterm infants. PMID- 8496774 TI - Magnesium deficiency in primary distal tubular acidosis. PMID- 8496775 TI - Intravenously administered immune globulin for Rh hemolytic disease. PMID- 8496776 TI - Neuroimaging in children with neurofibromatosis type 1. PMID- 8496777 TI - Prechewing food and parental nose blowing. PMID- 8496778 TI - Idiopathic arterial calcification of infancy: genetic studies. PMID- 8496779 TI - Cell cycle-specific growth inhibitory effect on human gingival fibroblasts of a toxin isolated from the culture medium of Actinobacillus actinomycetemcomitans. AB - A toxin isolated from the growth medium of Actinobacillus actinomycetemcomitans by ammonium sulfate precipitation was shown to inhibit irreversibly the multiplication of human gingival fibroblasts. DNA histograms from flow cytometric measurements showed that the cells accumulated preferentially in the G2 phase of the cell cycle. Such cells exhibited sheetlike protrusions, and an increased frequency of micronuclei was evident in cells treated with low concentrations of the toxin. Toxin-treated cells were viable for several weeks, as shown by staining with trypan blue and fluorescein diacetate, and the general cell metabolism as measured by oxygen consumption was unimpaired. PMID- 8496780 TI - Fluoridation effects on periodontal disease among adults. AB - Numerous studies report that water fluoridation reduces caries in children, but little current evidence exists about fluoridation's effects on the periodontal health of adults. To address this issue, we estimated fluoridation effects on periodontal disease among 1066 Washington state employees and their spouses, aged 20 to 34, with current residences divided evenly between fluoridated and nonfluoridated communities. Subjects were interviewed by telephone to collect residence histories, personal characteristics and other data. Each subject's lifetime years of fluoridation exposure (YFE) was calculated from the person's residence history and the U.S. Centers for Disease Control's Fluoridation Census. Oral assessments were conducted to measure the extent of periodontal disease. Relative to adults with no exposure, continuous lifetime exposure reduced the probability of attachment loss from 0.87 to 0.72. Similar benefits were obtained for bleeding gingiva and calculus. The estimates of fluoridation's benefits were not influenced by selection bias due to subjects' nonparticipation in the oral assessments. PMID- 8496781 TI - Characterization of hemolytic bacteria in subgingival plaque. AB - Three-quarters of the patients with periodontal diseases surveyed in this study had one or more distinct types of hemolytic bacteria in their subgingival plaque. Twelve different species of bacteria were identified, belonging to five genera (Actinomyces, Streptococcus, Staphylococcus, Prevotella, and Actinobacillus). Nine hemolytic isolates, consisting of four Prevotella denticola strains, two Actinomyces naeslundii genospecies 2 strains, and one each of P. melaninogenica, Streptococcus constellatus, and A. naeslundii genospecies 1 strains were characterized. Incorporation of pronase into blood agar medium inhibited hemolysis by all of the isolates, suggesting a proteinaceous component for each of their hemolysins. With one exception, hemolysin production appeared to be regulated by the concentration of environmental iron: exogenous hemin was found to inhibit hemolysin production, and the iron scavenging compound, 2,2'- dipyridyl, was found to promote hemolysin production by all of the strains except for the S. constellatus isolate. Genomic libraries of each of the hemolytic plaque isolates were prepared in Escherichia coli using pBR322. Hemolytic clones were isolated on blood agar medium containing ampicillin at frequencies ranging from 1-6.7 x 10(-4). Extensive restriction mapping revealed regions of homology in the case of clones derived from three P. denticola strains isolated from the same subjects. Two of the P. denticola-derived clones were virtually identical throughout the entrety of their > 5 Kb inserts. The clone derived from the third strain showed good homology to the other two within a 1.3 Kb region, but the flanking DNA showed no homology even though all three P. denticola isolates were shown to be clonally related by ribotyping.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496782 TI - Disturbances of gingival fibroblast population homeostasis due to experimentally induced inflammation in the cynomolgus monkey (Macaca fascicularis): potential mechanism of disease progression. AB - We have studied the relationship between perturbations of fibroblast turnover in inflamed gingiva of different severities. To perform detailed spatial analyses of gingival fibroblast progenitor cells, inflammatory cell infiltrates and blood vessels, 3 Cynomolgus monkeys with healthy periodontium and 2 with naturally occurring gingivitis and ligature-induced periodontitis were pulse-labeled with 3H-thymidine. Morphometric analyses of radioautographs from mid-sagittal supra alveolar gingival connective tissues of incisors were performed in sites subjacent to junctional sulcular and oral epithelium, in the body of the lamina propria and just superior to the alveolar crest. The percentage of fibroblasts incorporating 3H-thymidine label, expressed as the labeling index (LI), was higher subjacent to the sulcular epithelium in periodontitis (1.73 +/- 0.37) than in healthy sites (1.06 +/- 0.22). This was not statistically significant (0.05 < p < 0.1) due to the small number of animals used. The sites subjacent to the sulcular epithelium also exhibited the largest increase in lymphocyte density from health to gingivitis (p < 0.01). In contrast, the LI of fibroblasts subjacent to the oral epithelium was 5-fold higher in healthy (0.82 +/- 0.17) compared to periodontitis sites (0.13 +/- 0.09; p < 0.05). Labeled fibroblasts were found close to blood vessels in all compartments and in all disease states; distance to blood vessels was reduced in inflamed sites (p < 0.10). There were increased numbers of blood vessels per unit area in the lamina propria of gingivitis compared to healthy sites. However, there were no regional differences with respect to blood vessel numbers or area in sites subjacent to junctional epithelium with different disease states. The results indicate that: 1) experimentally-induced inflammation in the gingiva of Cynomolgus monkeys is associated with site-specific perturbations of cell turnover; 2) fibroblast progenitors are preferentially situated adjacent to blood vessels as in the periodontal ligament; 3) the vascular response to inflammation is a generalized increase in blood vessel numbers, but not their size; 4) reactive proliferation of fibroblasts may compensate for cell death in the lamina propria but is not detectable at the site of connective tissue attachment loss subjacent to the junctional epithelium. Failure to maintain the fibroblast progenitor population may be an important component of attachment loss in progressive periodontitis lesions. PMID- 8496783 TI - Increased oxidative product formation by peripheral blood polymorphonuclear leukocytes in human periodontal diseases. AB - We examined the oxidative burst (hydrogen peroxide-dependent oxidative product formation) of polymorphonuclear leukocytes (PMNL) in the peripheral blood from the patients with various types of periodontal diseases including localized juvenile (LJP), generalized juvenile (GJP) and adult periodontitis (AP). Heparinized peripheral blood was obtained from 15 LJP, 13 GJP and 52 AP patients and from 30 healthy control subjects. The oxidative product (2',7' dichlorofluorescein; DCF) formation of PMNL by stimulation with phorbol myristate acetate myristate acetate was evaluated by a rapid quantitative assay using flow cytometry. The results indicated that all patient groups contained variable populations with normal or increased DCF formation, while the control subjects exhibited DCF formation as a single population. No significant differences in average DCF formation were found among the three patient groups. Although individual patients gave various values, the average DCF formation of the three patient groups was much higher than that of the control group. Statistical analysis revealed a significant positive correlation between DCF formation and the clinical periodontal parameters on an individual basis. Furthermore, after initial periodontal treatment, DCF formation decreased to normal levels. These results suggest that the capacity of peripheral blood PMNL to mount oxidative burst reactions might reflect the inflammatory status of periodontal disease. PMID- 8496784 TI - Characterization of the wheat germ agglutinin-binding property of Treponema denticola. AB - Lectins were used to characterize glycoconjugates on the cell surface of Treponema denticola, a suspected periodontopathogen. Bacteria were first screened by light microscopy using fluorescein isothiocyanate-coupled lectins. Wheat germ agglutinin (WGA) showed a high reactivity to T. denticola. While the WGA-binding activity was accentuated following heating or detergent treatments of bacterial cells, the reaction was inhibited by incorporation of competing carbohydrates. Scanning and transmission electron microscope studies were conducted in order to characterize the distribution of the WGA-binding sites on the cell surface of T. denticola. Data from these studies confirmed that heat treatment increases the percentage of labeled profiles and suggest that the WGA-binding sites are concentrated on specific regions on the spirochete surface. Initial biochemical analysis indicated that the high reactivity to WGA resides in a peptidoglycan fraction. PMID- 8496785 TI - Reliability of filter-strip sampling of gingival crevicular fluid for volume determination using the Periotron. AB - This study explored gingival cervicular fluid (GCF) volumes as measured by the Periotron in an attempt to find a more objective measure of gingival inflammation that could be used in dental compliance studies. The first step in this process was to assess the reliability of the method of collecting and determining GCF volumes as described by the manufacturer. Collections of GCF from both the buccal and lingual surfaces of 6 teeth from 18 subjects with good to moderate plaque accumulation was accomplished. At a later time these same surfaces were retested for a comparison with the initial value for reliability determination. We found that only 23% of the tooth surface pairs varied by less than 20% and 57% of these pairs differed by at least 50%. These values were similar for both good and moderate plaque accumulation subjects. In these subjects, reliability measurements at individual tooth surfaces did not approach acceptable levels of reliability. However, when the GCF values from the 12 tooth surfaces were averaged for each subject, differences between the two measurements improved markedly. Sixty-one percent of these subject pairs differed by less than 20%. Therefore, the average GCF value from subjects with good to moderate plaque accumulations may be compared with reasonable accuracy. PMID- 8496786 TI - Transcription of the HIV-1 LTR is regulated by the density of DNA CpG methylation. AB - Transcription from the HIV-1 long terminal repeat (LTR) was shown to be inhibited by DNA CpG methylation both in vivo and in vitro. Enzymatic methylation of CpG sites localized within the LTR decreased the transcription of the CAT reporter gene, chloramphenicol acetyltransferase, as assayed by the transient expression of this gene in tissue culture. The inhibitory effect could be initially overcome, in trans, by the transactivator tat. As a function of time, the presence of tat had no observable effect on transcription, within the limits of detection sensitivity, suggesting that the level of basal transcription was reduced to very low levels. This effect is suggestive of the involvement of cellular CpG methylation-dependent inhibitory factors which have been characterized by other laboratories. These data imply that transactivation is reduced to low levels after longer periods of time when the DNA template is sparsely methylated. The transcriptional inhibitory process may involve proteins such as MeCP which may interact with methylated DNA more slowly and/or weakly. Conversely, densely methylated DNA was transcriptionally repressed immediately which suggests the rapid/strong association of the cellular inhibitory factor(s). The transcriptional inhibitory effect was also observed in an in vitro transcription run-off system. These data suggest that the methylation-mediated inhibition of transcription is directly affected by CpG methylation density and may involve other factors. PMID- 8496787 TI - Mutational analysis of the amino and carboxy termini of the HIV-2 Tat protein. AB - The transactivator proteins of HIV-1 and HIV-2, Tat-1 and Tat-2, are highly homologous in the center of each molecule but are divergent in the amino and carboxy termini. The structure of Tat-1 has been extensively characterized by mutagenesis studies, whereas little is as yet known specifically about the structure of Tat-2. To characterize the Tat-2 protein, we performed a mutational analysis of the amino and carboxy termini of the fully functional first exon (99 residues) of the Tat-2 protein. We found that deletion of residues 8 through 33 in the amino terminus drastically reduced transactivation activity, whereas deletion of residues 8 through 47 largely abolished transactivation activity. We also analyzed chimeric proteins in which the amino termini of the Tat-1 and Tat-2 proteins were exchanged precisely at the first cysteine in the cysteine-rich regions. Both chimeric proteins possessed very low levels of transactivation activity, indicating that the amino termini of Tat-1 and Tat-2 are not interchangeable. Truncation mutants in the carboxy terminus were analyzed and amino acid 90 at the end of the basic domain was found to be at or near the limit of carboxy residues that can be deleted without abolishing Tat-2 function. A Tat 2 mutant truncated after residue 84 within the basic domain was found to be a transdominant mutant able to inhibit wild-type Tat-1 and wild-type Tat-2 activities. Additionally, the results of immunoprecipitations suggested that deletions in the Tat-2 amino terminus can reduce protein stability. PMID- 8496788 TI - A dominant epitope of HIV-1 protease recognized by hamster monoclonal antibodies. AB - Monoclonal antibodies (mAbs) against HIV-1 protease (HIV PR), the essential protease of human immunodeficiency virus type 1 (HIV-1), were produced in Armenian hamsters. Studies of direct binding to synthetic peptides and inhibition of binding to intact protease by peptide competition showed that five mAbs recognized an epitope that includes the sequence LPGRWKPK (residues 38-45), which lies near the region of the protease called the flap. All of the mAbs react specifically with HIV PR in Western blots. Because of structural conservation of the epitope in the proteases of many HIV-1 isolates, mAbs to this epitope are likely to be useful for detection of HIV PR in field isolates of HIV-1. Also, mAbs specific for this epitope, which lies close to the flap of HIV PR, may be useful for functional studies of HIV PR and possibly for the design of inhibitors of protease activity that bind outside the enzyme's catalytic site. PMID- 8496789 TI - Clinical research units for the treatment of patients with HIV disease: operational issues and components needed to conduct clinical trials. AB - Clinical trials are of paramount importance for the development and evaluation of new therapies for patients with human immunodeficiency virus (HIV) disease. The objective of an HIV clinical research unit is to conduct high quality clinical research with patients who have HIV disease. The conduct of these research studies requires accurate and complete data collection. Coordination of the patients' primary care must be complemented by a working knowledge of the relevant ethical issues. In addition, technical, managerial, and clinical expertise is needed for conducting the trials and collecting data. To accurately plan the research, personnel and resource allocation should be periodically assessed. Clinicians, particularly those who have not previously conducted clinical trials or who are considering the incorporation of a research program into a primary care setting, must be familiar with these issues in order to create and supervise this type of clinical research unit. A smoothly running clinic observing a defined cohort of patients is attractive to government agencies and pharmaceutical sponsors for funding of clinical trials and research projects. PMID- 8496790 TI - Role of nutritional status and weight loss in HIV seroconversion among Rwandan women. AB - To investigate nutritional status and heterosexual human immunodeficiency virus (HIV) transmission, we performed a nested case-control study of sexually active, adult women in Kigali, Rwanda. Forty-five women who seroconverted during the 24 month study period were compared to 74 women who remained seronegative throughout the study. Seroconvertors and nonseroconvertors did not differ in preseroconversion serum levels of vitamin A, carotenoids, vitamin E, selenium, albumin, ferritin, or cholesterol. Weight loss, however, was a significant predictor of eventual HIV seroconversion. Subsequent seroconvertors lost an average of 1.5 kg during the first 6 months of the study compared with a 1.0-kg gain (p = 0.001) for nonconvertors. Nine of 27 (33%) seroconvertors, compared with one of 44 (2%) controls, lost at least 5 kg in the 6-month period beginning 1 year before their seroconversion (odds ratio, 21.5, 95% confidence interval 4.1 112). The association between weight loss and seroconversion was independent of other potential risk factors such as socioeconomic status, pregnancy, and genital ulcer disease. In addition to these findings for measured weight loss during follow-up, reported weight loss before enrollment was also a risk factor for subsequent seroconversion. Additional studies of heterosexual HIV transmission are needed to determine whether or not weight loss is causally related to susceptibility for HIV infection. PMID- 8496791 TI - Differences between men and women with HIV-related Pneumocystis carinii pneumonia: experience from 3,070 cases in New York City in 1987. AB - Although women make up the fastest growing group of persons with AIDS, studies of human immunodeficiency virus (HIV)-infected persons reported to date have included predominantly or exclusively men. We evaluated sex differences in sociodemographic characteristics, hospital characteristics, in-hospital resource use, and short-term mortality rates for 2,526 men and 544 women admitted for their first-episode of HIV-related Pneumocystis carinii pneumonia (PCP) in New York City in 1987. Compared with men, women were significantly less likely to be white (81% vs. 54%, p < or = 0.001) or have private health insurance (80% vs. 58%, p < or = 0.001), and more likely to be admitted through an emergency room (79% vs. 71%, p < or = 0.001) and receive care at hospitals that had less experience treating PCP (p < or = 0.001). Women were more likely than men to die in the hospital [33% vs. 24%; crude odds ratio = 1.56, confidence interval (CI) = 1.28-1.91, p < or = 0.001]. In a logistic regression model, the risk of death in the hospital was associated with age 60-65 years [adjusted odds ratio (AOR) = 4.19, CI = 2.13-8.21], not having private health insurance (AOR = 1.37, CI = 1.08 1.75), admission through the emergency room (AOR = 1.54, CI = 1.21-1.96), and receiving care at hospitals with less experience treating PCP (AOR = 1.63, CI = 1.15-2.30), but women were not significantly more likely to die in the hospital than men (AOR = 1.18, CI = 0.93-1.50). Poorer access to medical care as well as higher use of hospitals with less experience treating AIDS may account for the difference in mortality rates observed in women with HIV-related PCP. PMID- 8496792 TI - Purified protein derivative (PPD) and HIV infection in Cali, Colombia. PMID- 8496793 TI - Endemic HTLV-II infection among Tobas and Matacos Amerindians from north Argentina. PMID- 8496794 TI - Persistent lack of human immunodeficiency virus infection in intravenous drug users at very high risk. PMID- 8496795 TI - Attitudes of pregnant women toward routine human immunodeficiency virus antibody testing in Italy. PMID- 8496796 TI - Neurological disorders related to HTLV-I and HTLV-II. PMID- 8496797 TI - The HIV/AIDS epidemic: a current picture. PMID- 8496798 TI - Biology of prion diseases. PMID- 8496799 TI - Asking the right questions. PMID- 8496800 TI - 2,3-Butanedione monoxime (BDM) inhibition of delayed rectifier DRK1 (Kv2.1) potassium channels expressed in Xenopus oocytes. AB - DRK1 is a cloned K+ channel from rat brain with consensus sites for protein kinase-dependent phosphorylation that might be expected to be functionally regulated by phosphorylation. 2,3-Butane-dione-monoxime (BDM) chemically removes phosphate groups from many proteins, and its action on DRK1 channels was examined after expression of DRK1 cRNA in Xenopus oocytes. In two-microelectrode voltage clamp experiments, the application of BDM to the bath inhibited DRK1 current (ki = 16.6 mM, H = 0.96) rapidly and reversibly, with a time course similar to the time course of solution change within the bath. DRK1 current was inhibited at all potentials; the time course of current activation, deactivation and inactivation were unaffected by BDM. In inside-out patch-clamp experiments, the application of BDM to the cytoplasmic surface similarly inhibited channel activity rapidly and reversibly (ki = 10.7 mM, H = 1.01) in the absence of rephosphorylating substrates. These results are inconsistent with a phosphatase effect, because such an effect should be irreversible in cell-free, ATP-free patches. Instead, the results suggest that BDM can inhibit DRK1 channels directly from inside or outside of the membrane. PMID- 8496801 TI - Effects of a K+ATP channel opener, lemakalim, on systemic, coronary and regional vascular dynamics in conscious dogs: comparison with nifedipine, adenosine, nitroglycerin and acetylcholine. AB - The systemic, coronary and regional vascular responses to the K+ATP channel opener lemakalim were compared to other potent vasodilators (i.e., nifedipine, adenosine, nitroglycerin and acetylcholine). Experiments were performed in 12 conscious dogs 2 to 4 weeks after implantation of aortic catheters and flow probes on the ascending aorta, left circumflex coronary, celiac, mesenteric, renal and iliac arteries, and solid-state miniature pressure gauges in the left ventricular cavity. Dose-response curves induced by bolus injection (i.v.) were examined. For doses that reduced total peripheral resistance by 22%, lemakalim reduced celiac (-28 +/- 2%), mesenteric (-24 +/- 3%), renal (-17 +/- 3%) and iliac (-18 +/- 3%) vascular resistances (i.e., by amounts similar to those observed with the other vasodilators, except for adenosine, which increased renal resistance). At these doses, lemakalim induced a greater decrease (-52 +/- 3%) (P < .05) in coronary resistance, as compared with nifedipine (-35 +/- 3%), adenosine (-38 +/- 3%), nitroglycerin (-25 +/- 2%) and acetylcholine (-32 +/- 3%). However, when near maximal vasodilation was elicited, adenosine elicited the greatest (P < .05) decrease in coronary resistance (-81 +/- 1%), as compared with lemakalim (-74 +/- 2%), nifedipine (-67 +/- 2%), nitroglycerin (-63 +/- 2%) and acetylcholine (-72 +/- 1%). Both the time to maximal increases in regional blood flow and the time for recovery in all vascular beds were significantly prolonged for lemakalim compared with the other vasodilators. Thus, the K+ATP channel opener lemakalim dilates the coronary bed out of proportion to other vascular beds, is relatively more potent at lower doses than other vasodilators and exhibits a delayed and more prolonged action in all regional vascular beds. PMID- 8496802 TI - Identification of octopaminergic agonists with selectivity for octopamine receptor subtypes. AB - Previous studies utilizing relatively nonselective octopamine (OA) agonists have suggested that differences may exist between the pharmacological responses of Gs linked OA receptors found in various insect tissues and species. The present experiments identify and characterize two structurally related phenyl(imino)imidazolidine (PII) derivatives that demonstrate a significant degree of OA receptor subtype selectivity and, when used in concert, are able to distinguish tissue- and/or species-related differences in OA receptor response. In membrane preparations, 2,4,6-triethyl-PII (TEP) showed > 60-fold selectivity for activating adenylate cyclase in the firefly light organ vs. that in Manduca sexta nerve cord, whereas 2,4,6-trimethyl-PII (TMP) showed > 2-fold selectivity for activating adenylate cyclase in Manduca nerve cord vs. that in the light organ. Within the same tissue, the potency ratio for TEP/TMP was 29 in the light organ and 0.2 in the nerve cord, a degree of selectivity much greater than that of other PII analogs examined. Corresponding physiological measurements of octopaminergic response correlated well with biochemical measurements. TEP was 24 fold more potent than TMP for OA-mediated light emission in intact firefly light organs, whereas TMP was more than 3-fold more potent than TEP as an antifeeding agent in Manduca. These results indicate that the PII analogs, TEP and TMP, should prove quite useful for characterizing and differentiating OA receptor subtypes in various tissues and species. In addition, these findings provide further evidence that light emission in fireflies and disruption of feeding in Manduca involve Gs-linked OA receptors, subtypes of which are distributed differently in the end organs of these two species. PMID- 8496803 TI - 5-Methyl-4H-3,1-benzoxazin-4-one derivatives: specific inhibitors of human leukocyte elastase. AB - Inhibitors of human leukocyte elastase (HLE) may exert potent therapeutic effects on pulmonary emphysema, adult respiratory distress syndrome and other diseases involving tissue degradation. 7-(4-Chlorophenylsulfonyl-L-glutanyl)amino-5-methyl 2-isopro pylamino-4H-3,1- benzoxazin-4-one (TEI-5624) and 7-(4 chlorophenylsulfonyl-L-lysyl)amino-5-methyl-2- isopropylamino-4H-3,1-benzoxazin-4 one (TEI-6344), two derivatives of 5-methyl-4H-3,1-benzoxazin-4-one, showed strong and highly specific inhibition of human sputum elastase (HSE), which is equivalent to HLE, with Ki values of 6.91 and 16.3 nM, respectively. The selectivity of TEI-5624 for HSE vs. several proteinases ranged from 300-fold to 45,000-fold in favor of HSE. TEI-5624 and TEI-6344 also efficiently prevented degradation of insoluble elastin by stimulated polymorphonuclear leukocytes. The elastase inhibitory capacity of these compounds was not affected by treatment with stimulated polymorphonuclear leukocytes or Pseudomonas aeruginosa-origin elastase. When administered intratracheally to hamsters. TEI-5624 and TEI-6344 were eliminated from the lung with half-times of 85 and 240 min, respectively. In acute injury induced by intratracheal administration of HSE in hamsters, these compounds significantly suppressed pulmonary hemorrhage when administered intratracheally (1 mg/kg) either 30 or 240 min before challenge with HSE (1 mg/kg). HSE-induced emphysema in hamsters was also prevented by TEI-5624 (1 mg/kg) administered intratracheally 7 hr after HSE administration (1 mg/kg). These results suggest that TEI-5624 and TEI-6344 may be useful therapeutic agents for the treatment of HLE-mediated diseases. PMID- 8496804 TI - Selective block of transient Ca channel current in mouse neuroblastoma cells by U 88779E. AB - Antioxidants and T-type Ca channel antagonists are neuroprotective during ischemia or other central nervous system traumas. U-88779E (1-[(4-chlorophenyl phenyl)-methyl]-4-[(7-methoxy-5-isopropyl- 2,4,6-cycloheptatrien-1-one)-2 methyl]piperazine) has been shown to have both antioxidant activity and the ability to block Ca fluxes in cardiac microsomes. In this study, we examined the effect of U-88779E on Ca, Na and K channels in a neuronal cell line, N1E-115 cells. The drug blocked transient barium current (IBa) through low-threshold Ca channels (T-type) with little effect on other noninactivating IBa including the nifedipine-sensitive one. The drug at 20 microM reduced transient IBa at a constant rate, -7.2% of the control per min, and abolished the current within 15 min. This implies a continuous accumulation of the drug in cell membranes probably because of its high lipophilicity (log P = 7.003). U-88779E also blocked Na and K currents but at a rate about 8 times slower than that observed with transient IBa. Further studies on interactions of the drug with T-channels revealed that the drug had no effect on the shape of current-voltage curve, activation and inactivation kinetics, and steady-state activation curve. The drug, however, induced a hyperpolarizing shift in steady-state inactivation curve and became more potent under conditions where the channels in inactivated states prevail. These observations are consistent with the view that U-88779E has a higher affinity to T-type channels in inactivated states than in resting or open states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496805 TI - Correlation of (-)N6-phenylisopropyladenosine blood levels with cardiac responses in the anesthetized guinea pig. AB - This study was designed to develop a high-performance liquid chromatography-based analytical method to measure the blood concentration of (-)N6 phenylisopropyladenosine (R-PIA) in order to correlate such levels with cardiac responses, and to determine the pharmacokinetics of R-PIA. Experiments were carried out in anesthetized adult guinea pigs instrumented for measurement of the surface ECG. After i.v. (50 micrograms/kg; n = 9) or i.p. (3.5 mg/kg; n = 5) administration of R-PIA, the atrial rate and P-R interval were determined, and arterial blood samples (0.5 ml) were collected. The R-PIA content of plasma ultrafiltrates was determined by reversed-phase high-performance liquid chromatography. The ratio of R-PIA concentrations in whole blood and in ultrafiltrated plasma (free or unbound) at 35-37 degrees C was 2.51 +/- 0.10 (n = 7) and was relatively independent of R-PIA concentration. The concentration of unbound R-PIA in whole blood correlated well with cardiac responses. Two distinct patterns of cardiac response to varying R-PIA levels were observed. In 4 of 14 animals, R-PIA caused a prolongation of the P-R interval at a relatively constant atrial rate, whereas in 10 animals, R-PIA caused both a slowing of atrial rate and a prolongation of the P-R interval. An increase in the unbound concentration of R-PIA caused a decrease in atrial rate and an increase in P-R interval. Unbound R-PIA was rapidly cleared from blood (CL = 40 +/- 7 ml/kg/min) and had a large volume of distribution (VSS = 1.45 +/- 0.21 L/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496806 TI - The ATP-sensitive potassium channel blocker glibenclamide (glyburide) does not abolish preconditioning in isolated ischemic rat hearts. AB - Previous studies have indicated that the ATP-sensitive potassium channels blocker glibenclamide (glyburide) can abolish preconditioning in canine models of myocardial ischemia. Recently, an isolated rat heart model of preconditioning has been developed that may be ideal for studying the mechanisms of preconditioning. In the present study, we determined the effect of glyburide on preconditioning in isolated rat hearts. Rat hearts were isolated and retrogradely perfused with oxygenated Krebs'-Henseleit solution. They were then subjected to four periods of total global ischemia of 5-min duration, separated by 5-min reperfusion. The hearts were then subjected to 30-min global ischemia followed by 30-min reperfusion and contractile function and lactate dehydrogenase release determined. Non-preconditioned hearts sustained severe damage. Glyburide (1-100 microM) pretreatment had no effect on the severity of 30-min global ischemia and 30-min reperfusion. Preconditioning caused significant improvements in reperfusion contractile function (25-fold increase in left ventricular developed pressure) and reductions in reperfusion lactate dehydrogenase release and reperfusion end diastolic pressure (contracture). Glyburide had modest preischemic cardiodepressant and vasoconstrictor effects at 1-30 microM, whereas 100 microM caused a 50% reduction in preischemic coronary flow. Despite these effects, none of these concentrations of glyburide affected the efficacy of preconditioning. These studies indicate that preconditioning in isolated rat hearts does not occur via a glyburide- (and thus presumably ATP-sensitive potassium channel) sensitive mechanism. PMID- 8496807 TI - Studies on the neuronal circuits involved in the discriminative stimulus effects of 5-hydroxytryptamine1A receptor agonists in the rat. AB - Rats were trained to discriminate 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT, 0.1 mg/kg i.p.) or 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT, 1.25 mg/kg i.p.), a selective and nonselective 5-hydroxytryptamine1A (5-HT, serotonin) receptor agonist, respectively, from saline in a two-lever procedure. The selective 5-HT1A receptor agonist ipsapirone substituted completely for 8-OH-DPAT (ED50, 1.52 mg/kg) and 5-OMe-DMT substituted partially for 8-OH-DPAT, whereas 8 OH-DPAT (ED50, 0.07 mg/kg) and ipsapirone (ED50, 4.15 mg/kg) substituted completely for 5-OMe-DMT. These results suggest that the discriminative stimulus properties of both 8-OH-DPAT and 5-OMe-DMT are 5-HT1A receptor mediated, although 5-OMe-DMT may involve an additional interaction with other 5-HT receptor subtypes. 5-OMe-DMT substituted for 8-OH-DPAT after application in the lateral ventricle (ED50, 3.0 micrograms/rat) and the dorsal raphe nucleus (DRN, 1.1 micrograms/rat). After application in the DRN (ED50 range, 1.4-5.0 micrograms/rat) and the median raphe nucleus (2.3 micrograms/rat), and after bilateral application into the CA-4 region of the dorsal hippocampus (4.1 micrograms/rat), 8-OH-DPAT also produced responding on the 8-OH-DPAT lever. Ipsapirone also substituted for 8-OH-DPAT after application into the DRN and the hippocampus (ED50S, 38 and 62 micrograms/rat, respectively). The 5-HT1A mixed agonist-antagonist (1-(2-methoxyphenyl) 4-[4-(2-pthalimido)butyl]piperazine, i.p. NAN-190) attenuated the discriminative stimulus effects of 8-OH-DPAT injected i.p. (0.1 mg/kg), into the DRN (10 micrograms) or into the hippocampus (2 x 10 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496808 TI - Role of neurotensin in the nucleus raphe magnus in opioid-induced antinociception from the periaqueductal gray. AB - These studies examined the role of the neurotensinergic projections extending from the periaqueductal gray (PAG) to the nucleus raphe magnus (NRM) on the inhibition of the tail-flick reflex produced by microinjection of morphine or beta-endorphin in the PAG. Neurotensin (3-30 nmol) or the partial agonist [D Trp11] neurotensin (100 and 300 pmol) microinjected into the NRM of awake rats produced a dose-dependent inhibition of the tail-flick response lasting 90 to 150 min. Lower doses of neurotensin (0.03-0.3 nmol) produced a hyperreflexive tail flick response 10 min after injection, which correlated with a decreased hot plate latency. Additionally, a dose of [D-Trp11]neurotensin (3 pmol) that had no intrinsic activity antagonized both the antinociceptive as well as hyperreflexive responses of neurotensin. Morphine (6 nmol) injected into the PAG produced an inhibition of the tail-flick response that was enhanced by injection of [D Trp11]neurotensin (3 pmol) into the NRM. In contrast, injection of [D Trp11]neurotensin (3 pmol) into the NRM had no effect on the inhibition of the tail-flick produced by beta-endorphin (10 nmol) in the PAG. Antineurotensin antiserum yielded results similar to those obtained with [D-Trp11]neurotensin. Although neurotensin was found to produce changes in tail skin temperature, it was possible to dissociate these effects from changes in tail-flick latency. These data suggest that neurotensin produces both antinociceptive and hyperalgesic responses when injected into the NRM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496809 TI - Cocaine and its metabolites constrict cerebral arterioles in newborn pigs. AB - We examined the effect of cocaine and several of its metabolites on cerebral arterioles in newborn pigs and evaluated the sympathomimetic properties of each of the compounds as a vasoactive mechanism. After piglets were equipped with closed cranial windows, compounds were suffused over the brain surface and pial arteriolar diameter (base line, approximately 100 microns) was recorded. Cocaine, cocaethylene, norcocaine, ecogonine, benzoylecgonine and ecgonine methylester each caused a dose-dependent (10(-8) M to 10(-4) M) decrease in pial arteriolar diameter: maximum percent reductions in diameter induced by each compound (10(-4) M) were, respectively, 12 +/- 1, 12 +/- 2, 11 +/- 1, 7 +/- 1, 7 +/- 2 and 5 +/- 1. In analyzing the dose-response curves, cocaethylene was the most potent vasoconstrictor, followed by cocaine, norcocaine and then ecogonine, benzoylecgonine and ecgonine methylester. Cerebral vasoconstriction induced by topically applied norepinephrine was enhanced by cocaine, norcocaine and cocaethylene, but not by the other three metabolites. Topical application of phentolamine failed to block vasoconstriction elicited by cocaine or its metabolites, although it did block vasoconstriction elicited by norepinephrine. These observations indicate that cocaine and its metabolites constrict the immature cerebrovasculature by a non-sympathomimetic mechanism. PMID- 8496810 TI - Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens. AB - Adult male rats were trained to intracranially self-administer cocaine (50-100 pmol/100 nl infusion) into the medial prefrontal cortex and to simultaneously deliver an infusion of vehicle (100 nl of artificial cerebrospinal fluid) to a littermate control. When stable base lines of responding were obtained, each rat was implanted with an indwelling jugular catheter for the administration of radioactive precursors for the biogenic amine neurotransmitters. When stable rates of responding were re-established, the animals were infused with the radiolabeled precursors at the beginning of the behavioral session and were sacrificed 60 or 90 min later. Discrete response-contingent infusions of cocaine into the medial prefrontal cortex resulted in decreases in the turnover of dopamine and serotonin and increases in norepinephrine utilization at the site of self-injection compared to vehicle-infused controls. In contrast, DA turnover was significantly increased in the ipsilateral nucleus accumbens of the self administering rats. These data demonstrate that discrete response-contingent cocaine infusions into the medial prefrontal cortex activate DA innervations of the nucleus accumbens, likely through descending pathways affecting A10 dopaminergic cell bodies, suggesting that neuronal activity similar to that observed after i.v. self-administration is initiated with the ICSA of the drug. PMID- 8496811 TI - Characterization of angiotensin receptors mediating the neuromodulatory effects of angiotensin in the vas deferens of the rabbit. AB - The objective of the present study was to characterize receptors mediating the neuromodulatory effects of angiotensin in the prostatic vas deferens (VD) of the rabbit by using losartan (DuP 753) and PD 123177, two nonpeptide ligands interacting preferentially at the AT1 and AT2 sites, respectively. Field stimulation of the VD (3 Hz, 1 msec pulse duration, 50 V for 10 sec) resulted in a biphasic contractile response, consisting of an initial phasic component (Phase 1) and a late tonic component (Phase 2). Desensitization of purinoceptors with alpha-beta methylene ATP (3 microM) abolished completely both components of the biphasic response. Angiotensin-II (A-II) and angiotensin-III (A-III) produced a concentration-dependent potentiation of Phase 2, with A-II being approximately 10 fold more potent than A-III. Losartan (0.03, 0.3 and 3 microM) produced parallel, concentration-dependent dextral shifts of the concentration effect curve to A-II without altering the maximum response (Schild analysis: slope = 1.18, pA2 = 8.5). In a separate series of experiments, field stimulation of the VD (0.1 Hz, 1 msec pulse duration, 80 V) resulted in a monophasic twitch response (Phase 1), which was also abolished by desensitization of purinoceptors. Both A-II and A-III produced a concentration-dependent inhibition of the Phase 1, with A-III being as potent as A-II but producing a significantly greater maximum response. Losartan (0.1 and 0.01 microM) antagonized the inhibitory effects of A-II and A-III in an unsurmountable manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496812 TI - Cardioprotection in ischemic rat hearts with the SH-containing angiotensin converting enzyme inhibitor zofenopril: possible involvement of the ATP-sensitive potassium channel. AB - The SH-containing angiotensin-converting enzyme (ACE) inhibitors zofenopril and captopril have been shown to protect the ischemic myocardium independently of ACE inhibition. Zofenopril (30-100 microM) enhanced reperfusion contractile function and reduced lactate dehydrogenase release. The cardioprotective activity of zofenopril was stereoselective in isolated globally ischemic rat hearts (S, S,R stereoisomer of zofenopril was inactive). The role of ATP-sensitive potassium channel (KATP) activation was investigated using two structurally different KATP blockers, 1 microM glyburide and 100 microM sodium 5-hydroxydecanoate. The cardioprotective activity of 100 microM zofenopril was abolished by both KATP blockers. Cardioprotection with the SH-containing compound n-acetyl cysteine (300 microM) was also reversed by glyburide, further demonstrating that ACE inhibition is not a prerequisite. Isobolographic analysis demonstrated that cotreatment with zofenopril and the KATP opener cromakalim resulted in a super-additive response in the ischemic myocardium. KB analysis demonstrated glyburide was a noncompetitive antagonist in the presence of zofenopril and a competitive antagonist in the presence of cromakalim. Zofenopril has been reported to cause relaxation in aortic smooth muscle rings via an endothelium-dependent component. This relaxation was shifted to the right by both glyburide and sodium 5 hydroxydecanoate. Isobolographic analysis of zofenopril and cromakalim in smooth muscle also demonstrated a super-additive response. These results demonstrate for the first time a link between the cardioprotective effects of the SH-containing compounds zofenopril and n-acetyl cysteine and the KATP. The activity appears to be a receptor-mediated event which occurs in a manner different from classical KATP openers such as cromakalim. PMID- 8496813 TI - Xenopsin, neurotensin, neurotensin(8-13) and N-acetyl-neurotensin(8-13) inhibit vascular leakage in rats after tissue injury. AB - Swelling, edema and leakage of proteins from the vascular compartment are immediate inflammatory responses of living tissues to local injury. Xenopsin, neurotensin (NT), NT(8-13) and NAcNT(8-13) administered to male rats anesthetized with sodium pentobarbital 60 mg/kg i.p. inhibited swelling and edema in the paw induced by immersion in 58 degrees water for 1 min. The ED50 values for xenopsin. NT, NAcNT(8-13) and NT(8-13) for reducing heat-induced edema were 0.9, 1.5, 1.9 and 2.1 nmol/kg i.v., respectively. NAcNT(8-13) was chosen as a prototype for further studies because, compared to NT, it had minimal hypotensive effects. NAcNT(8-13), 4 nmol/kg i.v., injected 10 min before mechanical injury to muscle, produced by a 4 cm midline surgical incision in the rectus abdominis, or before freeze injury to the cortex, produced by applying a cold probe (-50 degrees C) to the skull for 4 min, reduced vascular leakage, measured as area of Monastral blue staining of the injured tissues. NAcNT(8-13), 4 nmol/kg i.v., also attenuated pulmonary edema induced by epinephrine bitartrate 10 micrograms/kg i.v. The ability of NAcNT(8-13) to inhibit vascular leakage was not linked to its transient hypotensive effects and it was not blocked by alpha-helical-CRF(9-41), a putative CRF receptor antagonist, or by chlorpheniramine, a H1-histamine receptor antagonist. PMID- 8496814 TI - Differential regulation of prostaglandin synthesis by angiotensin peptides in porcine aortic smooth muscle cells: subtypes of angiotensin receptors involved. AB - We determined the role of AT1 and AT2 angiotensin receptors as mediators of prostaglandin (PG) release and mobilization of intracellular Ca++ in cultures of porcine vascular smooth muscle cells (VSMC) with subtype-selective angiotensin (Ang) II receptor antagonists. The binding of [125I]Ang II to porcine VSMC showed an equilibrium constant (KD) of 0.52 nM and a binding capacity (Bmax) of 14.8 fmol/mg protein. Using the AT1 antagonists DuP 753, its metabolite EXP 3174, and L-158,809, [125I]Ang II binding was displaced in a clearly biphasic manner, indicating the presence of two binding sites. Consistent with this, the AT2 antagonist CGP 42112A also displayed a biphasic curve, whereas another AT2 antagonist, PD 123177, showed a 20% reduction in binding. Ang I, Ang II and Ang (1-7) stimulated PGE2 as well as PGI2 synthesis in a dose-dependent pattern. Ang II but not Ang I or Ang-(1-7) also caused an increase in the intracellular concentration of Ca++. Ca++ mobilization by Ang II was blocked by the AT1 antagonist DuP 753, but not by the AT2 antagonists. Ang II- and Ang I-stimulated (10 nM) PG production was attenuated by all three AT1 antagonists. However, both CGP 42112A (100 nM) and PD 123177 (100 nM) also attenuated PG release in response to Ang II. The enhancement in PG release by Ang I (10 nM) was significantly reduced by CGP 42112A (100 nM), but not by PD 123177 (1 microM). Of the AT1 antagonists, only high doses of DuP 753 or L-158,809 partially reduced the Ang-(1 7)-induced release of PG. CGP 42112A was ineffective for blocking Ang-(1-7) stimulated PG release. Ang-(1-7)-stimulated PGE2 and PGI2 production was significantly reduced by PD 123177. Unlike DuP 753 or L-158,809, but similar to the sarcosine antagonists, EXP 3174 (10 nM) abolished the angiotensin peptide induced PG production. These data show that Ang I and Ang II stimulate PGE2 and PGI2 release via activation of both AT1 and AT2 receptors in porcine VSMC. Ang II stimulates intracellular Ca++ mobilization via activation of AT1 receptors only. Because Ang-(1-7) enhanced PGE2 and PGI2 release via activation of angiotensin receptors having greater affinity for PD 123177 than CGP 42112A, although CGP 42112A showed a greater ability to block the Ang I response, these data further suggest differences in these two compounds at AT2 receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8496815 TI - Dosing rate-dependent relationship between propranolol plasma concentration and beta-blockade. AB - The effect of propranolol dosing rate on beta-blockade was studied in human volunteers after administration of a conventional tablet and a sustained release capsule. The slope of the plot of the percentage of reduction in the heart rate against log plasma propranolol concentration was significantly greater after administration of a sustained release capsule than after administration of a conventional tablet. A marked leftward shift of the plasma concentration-response curve was also observed in rabbits as the infusion rate was decreased over the same infusion period. This shift was not altered by pretreatment with 6 hydroxydopamine and plasma catecholamine levels were not affected by the rate of infusion, indicating that the contribution of sympathetic activation to the effect was minimal. By contrast to the anticlockwise hysteresis of the temporal response after propranolol, no such hysteresis was found with the more hydrophilic beta-adrenoceptor antagonist atenolol, or was there any leftward shift in the plasma concentration- response relationship. Data from the isolated guinea pig atrial preparation also showed anticlockwise hysteresis and a leftward shift of the concentration-response curve at a low propranolol input rate, whereas no shift was observed with more hydrophilic beta-blockers such as atenolol, pindolol and metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496816 TI - Aging effects on stereoselective pharmacokinetics and pharmacodynamics of verapamil. AB - Pharmacokinetics and pharmacodynamics were studied after separate single 15-min infusions of each of verapamil's enantiomers (d, 10-11 mg/kg; l, 0.10-0.11 mg/kg) in 16 healthy non-smoking subjects ranging in age from 24 to 40 (young) and from 63 to 83 years (elderly). Verapamil clearance was found to be decreased in an age related stereoselective manner, with significant reductions in l-verapamil clearance in older subjects (P < .03), but no age-related change in d-verapamil clearance. Greater l- vs. d-verapamil clearance rates were only seen in younger male subjects. Trends for increased elimination half-lives for both enantiomers were seen with increasing age (for d-, P < .09, l- P = .10). Protein binding was stereoselective, with greater binding of d- vs. l-verapamil in both age groups (P < .0001) with no age-related differences in binding detected. Vd beta was greater for d- vs. l-verapamil (P < .05). l-Verapamil was more potent than d-verapamil (P < .001) for all pharmacodynamic variables measured. Both verapamil enantiomers decreased blood pressure (P < .0001), increased P-R intervals during sinus rhythm (P < .0001) and atrioventricular Wenckebach block cycle lengths (P < .0001) and transiently increased heart rate (P < .0001) in both young and elderly subjects. Age-related differences in responses were seen for blood pressure (greater decreases in systolic pressure in the elderly after d-verapamil, P < .002), heart rate (smaller and only transient increases followed by decreases after d verapamil) and P-R intervals during sinus rhythm (less prolongation in the elderly after both enantiomers, P < .02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496817 TI - In vitro and in vivo characterization of an A1-selective adenosine agonist, RG14202. AB - In this report, we demonstrate that the adenosine agonist N-5'-ethyl-N6 (cyclopentyl) adenosine-5'-uronamide (RG14202) is a vasorelaxant in porcine coronary arterial rings (EC50 = 0.37 +/- 0.054 microM; n = 19). This vasorelaxation (VR) occurs despite RG14202 being 275-fold selective for the rat brain A1 receptor. VR in response to RG14202 was attenuated markedly by the nonselective adenosine antagonist CGS15943, whereas 8-cyclopentyl-1,3 dipropylxanthine (DPCPX), a highly selective A1 antagonist, had only a small inhibitory effect. In contrast, the potassium channel blocker glybenclamide attenuated RG14202-induced VR markedly (85-fold), indicating that modulation of potassium channels is likely involved. In carotid arterial rings, RG14202 was approximately 5 times less potent than in the coronary artery, suggesting that this compound may be more selective for the coronary vasculature. In anesthetized rats, i.v. administration of RG14202 caused a significant decrease in mean arterial pressure only at the highest dose (3 micrograms/kg). In comparison, heart rate was decreased dose-dependently with maximal changes at 3 micrograms/kg. Both the depressor and bradycardic responses could be antagonized with CGS15943. RG14202 increased renal, but had no effect on mesenteric or hindquarter vascular resistance. Glybenclamide pretreatment (20 mg/kg) did not significantly alter the effects of RG14202 on heart rate or regional vascular resistances; however, the depressor response to RG14202 was attenuated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496818 TI - Cardiac electrophysiologic and antiarrhythmic actions of 3,4-dihydro-1'-[2 (benzofurazan-5-yl) ethyl]-6-methanesulfonamidospiro [(2H)-1-benzopyran-2,4' piperidin]-4-one HCl (L-691,121), a novel class III agent. AB - The cardiac electrophysiologic and antiarrhythmic actions of 3,4-dihydro-1'-[2 (benzofurazan-5-yl)ethyl]-6-methyl-sulfonamid ospiro [(2H)-1-benzopyran-2,4' piperidin]-4-one HCl (L-691,121), a novel spirobenzopyran piperidine class III agent, were assessed in vitro and in vivo. In ferret isolated papillary muscles, L-691,121 significantly prolonged effective refractory period (EC25 = 13 nM) and elicited a modest positive inotropic effect. In guinea pig isolated ventricular myocytes, L-691,121 prolonged action potential duration by selectively blocking (IC50 = 4.4 nM) a rapidly activating and rectifying component of the delayed rectifier K+ current, Ikr. The class III activity of L-691,121 in isolated papillary muscles was reverse frequency-dependent, and reversed by hypoxic perfusion. L-691,121 modestly depressed spontaneous beating rate (-14%) in guinea pig isolated right atria at concentrations up to 3 microM. In anesthetized dogs, the i.v. administration of 10 to 100 micrograms/kg of L-691,121 significantly increased atrial and ventricular refractoriness and prolonged the electrocardiographic Q-T interval, but did not alter atrioventricular nodal, His Purkinje, atrial or ventricular conduction. In conscious dogs with spontaneous premature ventricular complexes at 48 hr after myocardial infarction, 10 to 1000 micrograms/kg i.v. of L-691, 121 failed to reduce premature ventricular complex frequency. However, in anesthetized dogs studied chronically (7.9 +/- 0.3 days) after infarction, 10 and 100 micrograms/kg i.v. of L-691,121 suppressed the induction of ventricular tachyarrhythmia by programmed stimulation in 8/14 (57%) and 11/14 (79%) dogs tested, respectively, and reduced the incidence of lethal ventricular arrhythmias triggered by a secondary myocardial ischemic event from 14/15 (93%) in vehicle controls to 5/14 (36%; P < .01) in L-691,121-treated (100 micrograms/kg i.v.) animals. The latter findings suggest the potential for L 691,121 to prevent the development of malignant ventricular arrhythmias in the setting of previous myocardial infarction. PMID- 8496819 TI - Gastrointestinal and hepatic first-pass elimination of 2',3'-dideoxyinosine in rats. AB - We previously reported a > 80% presystemic loss of 2',3'-dideoxyinosine (ddl) in rats after an oral dose. The present study investigated the extent of drug loss due to incomplete absorption and presystemic elimination by intestinal wall, liver and intestinal microflora. In vitro metabolism by tissue homogenates showed that the extraction by liver, duodenum, jejunum and ileum was 19.0, 0.5, 1.8 and 1.4%, respectively. Hence, metabolism by the intestinal wall contributed less to the first-pass metabolism than the liver. The in vivo first-pass elimination was determined by infusing ddl into the liver and different parts of the intestinal tract. The in vivo extractions of 12 and 200 mg kg-1 of ddl doses by the liver were 23 and 5%, indicating a concentration-dependent liver metabolism. The in vivo liver extraction at the low dose was similar to the in vitro extraction. The in vivo extraction was 10% in the duodenum and 73% in the ileum. The significantly higher in vivo intestinal extractions compared to the in vitro extractions indicate a loss due to factors in addition to intestinal wall enzyme metabolism. Incomplete absorption was ruled out, based on the undetectable excretion of ddl in feces after duodenal or ileal infusion. A 14% w/v solution of intestinal contents degraded ddl by 18 and 38% over 2 and 24 hr, respectively, at 37 degrees C. By linear extrapolation, a 100% w/v enzyme solution would degrade the entire dose within 1.5 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496820 TI - Tertatolol, a new beta-blocker, is a serotonin (5-hydroxytryptamine1A) receptor antagonist in rat brain. AB - The interaction of tertatolol (d,l-hydroxy-2'-t-butylamino-3'propyloxy-8 thiochromane HCl) with 5-hydroxytryptamine (serotonin; 5-HT) receptors in several brain areas were investigated. Both ligand binding techniques and an electrophysiological approach were used. First, the affinity of tertatolol for different 5-HT receptor subtypes was measured, as assayed by a competition binding experiment using specific ligands in several brain areas. It was found that (-)-tertatolol binds to 5-HT1 receptor subtypes in rat brain, particularly the 5-HT1A subtype in the hippocampus (Ki = 5.9 nM). (-)-Tertatolol showed much lower affinity for 5-HT1B (Ki = 118.4 nM), 5-HT1C (Ki = 699.6 nM) and 5-HT2 (Ki = 678.6 nM) receptors. The binding of tertatolol to hippocampal 5-HT1A receptors was stereospecific in that the affinity of (+)-tertatolol to these receptors (Ki = 311.6 nM) was about 20 times lower as compared to that of (-)-tertatolol. There was no significant binding of tertatolol to 5-HT1D, 5-HT3, alpha-1 adrenergic receptors or to the serotonin uptake site. Electrophysiological techniques were used to study the effects of (-)-tertatolol on the activity of 5-HT-containing neurons in the rat dorsal raphe nucleus. Acute i.v. injection of (-)-tertatolol caused a slight increase in the basal firing rate of the majority of 5-HT neurons studied. Pretreatment with (-)-tertatolol (1 mg/kg i.v.) significantly reduced the inhibitory effect of 8-hydroxy-2-(di-n-proylamino) tetralin (0.25-64 micrograms/kg i.v.) on the firing rate of dorsal raphe nucleus 5-HT neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496821 TI - Pharmacological characterization of FK1052, a dihydropyridoindole derivative, as a new serotonin 3 and 4 dual receptor antagonist. AB - (+)-8,9-Dihydro-10-dihydro-10-methyl-7-[(5-methyl-4-imidazolyl) methyl]pyrido [1,2-a]indol-6(7H)-one hydrochloride (FK1052) is a newly designed and synthesized 5-hydroxytryptamine (5-HT)3 receptor antagonist with 5-HT4 receptor antagonistic activity. This compound, as well as ondansetron and granisetron, dose-dependently inhibited the von Bezold-Jarish reflex, a 5-HT3 receptor-mediated response, after intravenous (i.v.) and intraduodenal (i.d.) dosing to rats. The ID50 values showed FK1052 (0.28 microgram/kg, i.v., 5.23 micrograms/kg, i.d.) to be more potent than ondansetron (5.23 micrograms/kg, i.v., 170 micrograms/kg, i.d.) and granisetron (0.70 micrograms/kg, i.v., 66 micrograms/kg, i.d.). Furthermore, bioavailabilities of the test drugs by ID50 ratio (i.d./i.v.) showed that FK1052(17) was better absorbed than ondansetron(33) and granisetron(94) and possessed a similar duration of action to that of ondansetron and granisetron. We also examined the effects on 2-methyl-5-HT-, 5-HT- and 5-methoxytryptamine induced contractions of guinea pig isolated ileum. FK1052, ondansetron and granisetron concentration-dependently inhibited 2-methyl-5-HT, a 5-HT3 agonist induced contraction. The pA2 values for the 5-HT3 receptor indicated that FK1052 (8.36) was 40 times and three times more potent than ondansetron (6.79) and granisetron (7.86), respectively. FK1052, unlike ondansetron and granisetron, inhibited the 5-HT4-mediated component of concentration-response curve to 5-HT. Furthermore, FK1052 suppressed 5-methoxytryptamine, a 5-HT4 agonist-induced contraction in a concentration-dependent but insurmountable manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496822 TI - Effect of in vivo microdialysis of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on the extracellular concentration of acetylcholine in the striatum of anesthetized rats. AB - 1,2,3,4-Tetrahydro-9-aminoacridine (THA, tacrine) is a potent cholinesterase (ChE) inhibitor which is under consideration for the treatment of Alzheimer's disease. This paper examines the effect of in vivo microdialysis of THA, THB-013 (an analog of THA) and physostigmine on the extracellular concentration of acetylcholine (ACh) in the striatum of anesthetized rat, as well as their effects on in vitro striatal ChE activity. In addition, the interaction of THA and physostigmine with cholinergic receptors in rat striatum has been investigated. All three drugs inhibited ChE activity and increased the extracellular concentration of ACh in a concentration-dependent manner. In the presence of THA, atropine induced a smaller increase in extracellular ACh concentrations than it did in the presence of physostigmine, under experimental conditions in which THA (100 microM) and physostigmine (10 microM) produced an equivalent effect on ChE activity. THA bound significantly to both muscarinic and nicotinic receptors in rat striatum, whereas physostigmine did not show significant binding. THA (100 microM) and physostigmine (10 microM) produced an additive effect on the extracellular concentration of ACh, and the addition of THA (10 microM) to physostigmine (1 microM) produced further inhibition of in vitro ChE activity. 4 Aminopyridine (100 microM), a K+ channel blocker, showed no detectable effect by itself on the extracellular concentration of ACh, however, it significantly increased the extracellular concentration of ACh in the presence of physostigmine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496823 TI - Trichloroethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in nodose ganglion neurons from the adult rat. AB - Trichloroethanol (TCEt) potentiated ion current mediated by 5-hydroxytryptamine (5-HT)3 receptors in isolated adult rat nodose ganglion neurons. The magnitude of potentiation of peak current amplitude increased with increasing TCEt concentrations from 0.5 to 5 mM. The rate of decay of current also increased as a function of TCEt concentration. Steady-state current was unaffected by TCEt at concentrations up to 10 mM. A high concentration of TCEt (25 mM) potentiated peak current but inhibited steady-state current. Potentiation appeared to involve an increase in agonist potency as the magnitude of potentiation of peak current decreased with increasing agonist concentration. Agonist application before TCEt treatment decreased the magnitude of potentiation elicited by 5 mM TCEt. These observations indicate that the potentiating action of TCEt arises from an increase in the efficacy with which 5-HT activates current. TCEt appears to facilitate transitions from closed to open states more readily than transitions from desensitized to open states. These observations are consistent with the hypothesis that 5-HT3 receptor function may contribute to the behavioral pharmacology of alcohols and related sedative/hypnotic agents. PMID- 8496824 TI - Arsenic in the sera of gallium arsenide-exposed mice inhibits bacterial growth and increases host resistance. AB - The objective of the present investigations was to evaluate whether the presence of gallium arsenide (GaAs) in the sera of exposed mice was sufficient to retard bacterial growth. Host resistance studies demonstrated that exposure of GaAs (50 200 mg/kg) produced an increased resistance to Streptococcus pneumoniae and Listeria monocytogenes (50-100 mg/kg GaAs) when microbial challenge occurred 24 hr after exposure. In contrast, exposed mice exhibited a profound and dose related decrease in resistance to the B16F10 melanoma. Serial dilutions of GaAs (0.039-5 mg/ml) were added to BHI broth and cultures were innoculated with either S. pneumoniae or L. monocytogenes. GaAs slowed the growth of both organisms with a minimal inhibitory concentration (MIC) of 0.625 mg/ml. Sera from mice euthanized at various time intervals after exposure to vehicle (0.05% Tween 80 in saline) or GaAs (200 mg/kg) was also capable of retarding the growth of both organisms with the maximal inhibition noted for euthanization 24 hr after exposure. However, sera from GaAs-exposed mice (24 hr after exposure) was incapable of slowing the growth of the B16F10 melanoma. Addition of the arsenic binding compound meso-2,3-dimercaptosuccinic acid (100 microM) to sera from mice exposed to GaAs followed by innoculation with L. monocytogenes resulted in growth of this organism, which was comparable to growth observed in vehicle cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496825 TI - A bradycardic agent, UL-FS 49, increases atrial force and decreases ventricular force in isolated, perfused heart preparations of dogs. AB - We investigated the effects of a bradycardic agent, UL-FS 49 (1,3,4,5-tetrahydro 7,8-dimethoxy-3[3-[[2-(3,4-dimethoxyphenyl) ethyl]methylimino]propyl]-2H-3 benzazepin-2-on hydrochloride), on the sinus rate and atrial contractile force and the ventricular force in the isolated, blood-perfused right atrial and left ventricular preparations of the dog and the inhibition by UL-FS 49 of the negative cardiac responses to acetylcholine, adenosine and cromakalim. UL-FS 49 (0.003-3 mumol) decreased sinus rate, increased atrial force and decreased ventricular force in a dose-dependent manner. The threshold doses of UL-FS 49 (0.03 mumol) for atrial responses were smaller than that (1 mumol) for a ventricular response. The duration of bradycardia induced by UL-FS 49 was longer than the intropic one. Propranolol and atropine did not block the positive inotropic and negative chronotropic responses to UL-FS 49, respectively, in isolated atria. UL-FS 49 (0.1-3 mumol) dose-dependently inhibited the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and acetylcholine exogenously administered. UL-FS 49 at higher doses (1 and 3 mumol) attenuated the negative inotropic but not chronotropic responses to adenosine and cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496826 TI - Short-term effects of 2,4,5-trihydroxyamphetamine, 2,4,5 trihydroxymethamphetamine and 3,4-dihydroxymethamphetamine on central tryptophan hydroxylase activity. AB - In previous studies, we have reported the long-term effects of several metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on tryptophan hydroxylase (TPH) activity. In this study, the short-term effects of three metabolites of MDMA. 2,4,5-trihydroxyamphetamine (THA), 2,4,5-trihydroxymethamphetamine (THM) and 3,4-dihydroxymethamphetamine, and the in vitro effect of THA on TPH activity are reported. After short-term treatment, hippocampal TPH activity was decreased to 8 and 54% of control in response to THA and THM, respectively, but was unaltered after 3,4-dihydroxymethamphetamine. Incubating TPH from THM-treated rats with dithiothreitol under nitrogen failed to reverse the decrease in enzyme activity induced by THM treatment. THA also decreased tyrosine hydroxylase activity to 75% of control, whereas the enzyme activity remained unaltered by THM. The structural analog of THA, 6-hydroxydopamine, failed to reproduce the effect of THA on TPH activity; however, 5,6-dihydroxytryptamine decreased hippocampal TPH activity to 18% of control. In the in vitro study, the hippocampus and the striatum were incubated in varying concentrations of THA. After a 1-h incubation at 37 degrees C, hippocampal TPH activity was decreased to 83, 71, 68, 47 and 3% of control after exposure to 0.001, 0.01, 0.1, 0.5 or 5.0 mM THA, respectively; striatal TPH activity was reduced to 98, 95, 70, 54 and 17% of control, respectively. Incubating the enzyme under reducing conditions failed to restore the enzyme activity to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496827 TI - Effect of MCI-154, a cardiotonic agent, on regional contractile function and myocardial oxygen consumption in the presence and absence of coronary artery stenosis in dogs. AB - The effects of MCI-154 (6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)- pyridazinone hydrochloride.3H2O), a cardiotonic agent with calcium sensitizing actions, on regional contractile function and myocardial oxygen consumption (MVO2) were studied in the dog hearts with and without partial occlusion of the left anterior descending coronary artery and compared with those of dobutamine. Segment shortening by sonomicrometry, regional myocardial blood flow by microspheres and the oxygen content of coronary venous blood drawn from the ischemic left anterior descending coronary artery area were simultaneously measured. The ischemic zone segment shortening and left ventricular (LV) dP/dtmax were decreased after partial occlusion. The infusion of MCI-154 starting 20 min after ischemia improved the depressed segment shortening and LV dP/dtmax without increasing the ischemic zone MVO2 and regional myocardial blood flow. In the nonischemic hearts, MCI-154 did not increase MVO2 and coronary blood flow despite the augmentation of myocardial contractility. MCI-154 decreased LV end-diastolic pressure and systemic blood pressure. On the other hand, dobutamine failed to increase the ischemic zone segment shortening, but the drug increased MVO2, coronary blood flow and LV dP/dtmax in both ischemic and nonischemic hearts. These results indicate that MCI-154 alleviates the ischemic contractile failure without increasing myocardial oxygen demand. Thus, MCI-154 may be useful in the management of heart failure with reduced coronary reserve. PMID- 8496828 TI - Pharmacological characterization of SR 47436, a new nonpeptide AT1 subtype angiotensin II receptor antagonist. AB - SR 47436, 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]-1,3-diaza spiro[4,4]non-1-en-4-one, is a new potent and selective AT1 angiotensin II (AII) receptor antagonist. It competitively inhibited [125I]AII binding to AT1 subtype receptors in rat liver membranes (IC50 = 1.7 nM) and did not interact with AT2 subtypes in rat adrenal cortical membranes. In rabbit aorta, SR 47436 inhibited contractions induced by 10 nM AII (IC50 = 4.0 nM) and shifted AII contractile response curves to the right in a parallel fashion, without total recovery of the maximal response. The potency of SR 47436 was higher than that of the lead compound, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5- yl)biphenyl-4 yl)methyl]imidazole (DuP 753) (rat liver binding: IC50 = 16 nM; rabbit aorta: IC50 = 26 nM), and equivalent to saralasin (IC50 = 1.8 and 2.7 nM, respectively). The high specificity of SR 47436 was demonstrated by its lack of activity (IC50 > 10 microM) on various other receptors, ionic channels and antiports and rabbit aorta contracted by norepinephrine and KCl, and its lack of inhibition of renin and converting enzyme. In conscious rats, SR 47436 as well as DuP 753 (0.1 to 3 mg/kg, i.v., and 0.3 to 30 mg/kg, p.o.) antagonized the AII-pressor response in a dose-related manner. In conscious dogs, SR 47436 (1-10 mg/kg, p.o.) was a more potent antagonist of the AII pressor response than DuP 753. In conscious chronically implanted cynomolgus monkeys, SR 47436 antagonized the AII-pressor response at 1 mg/kg (89% i.v. and 66% p.o.) much more strongly than DuP 753 at 10 mg/kg (83% i.v. and 20% p.o.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496829 TI - Effects of MK-801 on the micturition reflex in the rat--possible sites of action. AB - The i.v. administration of MK-801 (dizocilpine), a noncompetitive N-methyl-D aspartate receptor antagonist, depresses reflex bladder contractions in the rat, suggesting that glutamatergic transmission may have an important role in the micturition reflex pathway. The site of action of MK-801 was analyzed in the present experiments by studying the effects of the drug in the following urethane anesthetized preparations: 1) intact rats, 2) decerebrate rats, 3) chronic spinal rats with transection at the T6-T8 segment and 4) intact rats in which the drug was administered via an intrathecal (i.t.) catheter at the L6-S1 spinal cord segments. Reflex bladder activity was monitored by measuring intravesical pressure under isovolumetric conditions and during a cystometrogram where the bladder outlet was open and voiding occurred. MK-801 (0.001-3 mg/kg i.v.) administered to the intact rats produced a dose-dependent suppression of the amplitude of reflex bladder contractions recorded during a cystometrogram. The ED50 and dose to produce maximal inhibition were 0.36 mg/kg and 3 mg/kg i.v., respectively. Doses of 0.3 to 1 mg/kg i.v. doubled the volume threshold for inducing micturition and decreased by 80% the voided volume in the intact rats. In decerebrate rats, reflex bladder contractions were also inhibited by MK-801 (ED50 = 0.055 mg/kg i.v.); however, in chronic spinal animals, even large doses of MK-801 (3-30 mg/kg i.v.) did not inhibit reflex bladder activity. MK-801 (6-78 micrograms) administered i.t. in the intact rats produced a dose-dependent suppression of the amplitude of reflex bladder contractions (ED50 = 13 micrograms). These results suggest that the inhibition of micturition reflex by MK-801 is mediated at least in part by an action on the lumbosacral spinal cord and is dependent on an intact pathway between the brain and spinal cord. PMID- 8496830 TI - Increase in extracellular acetylcholine level by sigma ligands in rat frontal cortex. AB - The effects of sigma ligands on the central acetylcholine (ACh) systems in the rat frontal cortex were examined. By using brain microdialysis techniques, we showed that nonbenzomorphan sigma ligands, (+)-3-(3-hydroxyphenyl)-N-(1 propyl)piperidine and 1,3-di(2-tolyl)guanidine (DTG) dose-dependently increased the extracellular ACh level in this area. Similarly, benzomorphan sigma ligands, (+/-)-pentazocine and (+)-N-allylnormetazocine [(+)-SKF-10,047] also increased the extracellular ACh level. The increase in extracellular ACh level elicited by (+)-SKF-10,047 was greater than that by (-)-SKF-10,047. Moreover, the (+)-SKF 10,047- and DTG-induced increase in the extracellular ACh level were reduced significantly by simultaneous administration of haloperidol, a putative sigma receptor antagonist, whereas the (+)-SKF-10,047-induced increase was unaffected by (+/-)-3-(2- carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a competitive N methyl-D-aspartate receptor channel antagonist. On the other hand, none of the sigma ligands tested in this study had any effects on acetylcholinesterase or choline acetyltransferase activity and sodium-dependent high affinity choline uptake site in the rat frontal cortex. Ranking of potency for increasing extracellular ACh level was in the following order: (+/-)-pentazocine > (+)-SKF 10,047 > (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine > DTG. This order was positively correlated with the order of binding potency for the (+)-[3H]SKF 10,047 binding site in the rat frontal cortex, but was not correlated with binding to the [3H]DTG, [3H]quinuclidinyl benzylate and [3H]AF-DX116 ([3H]11-[(2 [(dimethylamino)methyl]-1-piperidinyl)acetyl]-5, 11-dihydro-6H-pyrido[2,3 b][1,4]benzodiazepine-6-one) binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496831 TI - The action of amlodipine on human subcutaneous resistance arteries studied in vitro. AB - The effect of amlodipine, a dihydropyridine calcium antagonist which is largely ionized at physiological pH, was studied in human resistance arteries. Resistance arteries were isolated from subcutaneous fat and isometric force measured in a myograph. Amlodipine inhibited depolarization-induced contractions in a time- and concentration-dependent manner. The potency of amlodipine was markedly increased by depolarization of the resistance arteries by a physiological saline containing high potassium (40 mM) during exposure to amlodipine. The onset and offset of amlodipine-induced inhibition in these arteries was slow, but concentration dependent. Depolarization markedly increased the rate of onset of inhibition. The increase in potency of amlodipine under depolarized conditions could largely be accounted for by the increased rate of association of the drug. Possible use dependence of amlodipine was also examined in comparison with verapamil. The efficacy of both verapamil and amlodipine was increased in vessels which were repeatedly depolarized compared with vessels which were only activated once. This effect was more marked for verapamil than for amlodipine. The action of amlodipine in human resistance arteries is slow, shows marked voltage-dependence and, to a lesser degree, some use-dependence. These properties may be important in understanding the action of amlodipine in vivo. PMID- 8496832 TI - Similarities and differences in the postjunctional role for neuropeptide Y in sympathetic vasomotor control of large vs. small arteries of rabbit renal and ear vasculature. AB - Neuropeptide Y (NPY) coexists and is coreleased with norepinephrine (NE) from postganglionic sympathetic nerves. A correlation between the peripheral vascular effects of NPY and the diameter of blood vessels has been proposed: NPY induces a stronger contraction in small arteries, whereas the potentiation of the contractile responses induced by other vasoconstrictors, such as NE, seems to be restricted to larger arteries where NPY exhibits little or no direct contractile activity. The purpose of the present study was to systematically characterize in vitro the contractile effects of NPY per se and the effects of NPY on contractions evoked by exogenous NE in sequential artery segments of diminishing diameter from rabbit ear and kidney. The ability of NPY to evoke vasoconstriction increased with decreasing arterial diameter. The ability of NPY to potentiate exogenous NE-induced force of contraction was restricted to larger arteries where NPY had little or no contractile effect. The velocity of NE EC50-induced force development was augmented in the presence of NPY in all ear and intrarenal arteries. This is the first report of dissociation between the potentiation of exogenous NE-induced force of contraction by NPY and the increase in velocity of NE-induced force development by NPY. If, as has been suggested by other investigators, increased rate of contraction results in potentiation of contractile responses to short trains of adrenergic nerve stimulation, this latter finding suggests that a potentiation of contractile responses to short trains of adrenergic nerve stimulation occurs at all levels of the ear and intrarenal arterial vasculature. PMID- 8496833 TI - Unique natriuretic properties of the ATP-sensitive K(+)-channel blocker glyburide in conscious rats. AB - Small-conductance, ATP-sensitive K(+)-channels (KATP) localized in apical membranes of both thick ascending limb of the loop of Henle and cortical collecting duct cells may be involved in Na+ reabsorption and K+ secretion in the mammalian kidney. Possible pharmacologic tools to evaluate such an hypothesis may be the antidiabetic sulfonylureas which block K(+)-channels in pancreatic beta cells. In saline-loaded conscious rats, glyburide (GLY) dose-dependently increased urinary Na+ excretion with little change in urinary K+ excretion after i.p. administration (10-100 mg/kg). In renal clearance studies, GLY at 25 mg/kg i.v. increased Na+ excretion 350% during the first hour post-treatment without affecting K+ excretion, glomerular filtration rate, mean arterial pressure or heart rate. GLY at 50 mg/kg was no more natriuretic than the 25 mg/kg dose, whereas 12.5 mg/kg of GLY increased Na+ excretion 200%. The change in Na+ excretion produced by 25 mg/kg of GLY in streptozotocin-induced diabetic rats was significantly greater than the change after drug vehicle in these animals. It is unlikely that the natriuresis produced by GLY is secondary to changes in plasma insulin and/or glucose because the doses used were far above GLY's insulin releasing action (i.e., all natriuretic doses would have produced maximal insulin release) and GLY was natriuretic in streptozotocin-induced diabetic rats. It is possible that GLY interferes with reabsorption of Na+ by blocking KATP and thereby interrupting K+ recycling and Na(+)-2Cl(-)-K+ cotransport in the loop of Henle. PMID- 8496834 TI - Pharmacokinetics and bioreductive metabolism of the novel benzotriazine di-N oxide hypoxic cell cytotoxin tirapazamine (WIN 59075; SR 4233; NSC 130181) in mice. AB - The novel benzotriazine di-N-oxide SR 4233 (3-amino-1,2,4-benzotriazine-1,4-di-N oxide) shows high selective cytotoxicity toward hypoxic tumor cells. We investigated its pharmacokinetics and bioreductive metabolism in mouse plasma, brain, liver and tumor in vivo and also tumor metabolism in vitro. Plasma elimination T1/2 increased slightly with dose, and metabolite kinetics were dose dependent. Peak concentration and area under the curve0-infinity increased linearly with dose from 0.1 to 0.3 mmol kg-1 i.v. After 0.2 mmol kg-1 i.v., elimination was biphasic (T1/2 alpha < 2 min; T1/2 beta, 26.5 min). Peak plasma concentration and area under the curve0-infinity were 26 and 13.6 micrograms ml-1 hr, respectively. Peak plasma concentration for the two-electron reduction product SR 4317 (3-amino-1,2,4-benzotriazine-1-oxide) was 7 to 9 micrograms ml-1 and for the four-electron reduction product SR 4330 (3-amino-1,2,4-benzotriazine) peak plasma concentration was 0.5 to 1.0 micrograms ml-1. Identical results were obtained after i.p. administration. Oral dosing gave lower peak plasma drug concentrations (2-3 micrograms ml-1) but reasonable bioavailability (75%). SR 4233 underwent extensive bioreduction in KHT tumors. Tumor/plasma ratios (percentages) for SR 4233 were 32% compared to 174 (SR 4317) and 196% (SR 4330), respectively. Similar SR 4233 tissue/plasma percentages were obtained in RIF-1 and 16C tumors, but EMT6 tumors were markedly lower at 7%. Reduction also occurred with tumor homogenates in vitro (KHT = EMT6 > RIF-1). Conversion to SR 4317 and SR 4330 was more extensive in liver, with tissue/plasma percentages between 50 to 220 and 500 to 1800%, respectively. The brain showed a similar pattern to tumors. Urinary recoveries (0-8 hr) were low at 4.5% for SR 4233 and 0.4% for the reduced metabolites. A further 30% occurred as a glucuronide. Concentrations of SR 4233 required for effective in vitro cytotoxicity are achieved in vivo, and extensive bioreductive metabolism occurs in tumor and normal tissues. PMID- 8496835 TI - Effect of orogastric nicotine on rat gastric mucosal gel thickness, surface cell viability and intracellular pH. AB - Intracellular pH was measured in vivo using a fluorescent, microscopic technique in gastric surface cells of rats exposed to orogastric nicotine on an acute or chronic basis. Mucosae were superfused with solutions of pH 3 or pH 1.7 in order to examine the rate of intracellular acidification and recovery. In rats acutely exposed to nicotine, the response of intracellular pH to superfusion with acidic solutions was blunted with respect to control rats in a dose-dependent manner. In contrast, intracellular pH of rats chronically treated with nicotine had an exaggerated response with respect to control rats, with more rapid acidification and diminished ability to maintain intracellular pH in the physiologic range. Mucus gel thickness was increased after acute nicotine exposure in a dose dependent manner, whereas a dose-dependent decrease in thickness was seen after chronic nicotine exposure. Cell viability using the fluorescent vital dye propidium iodide was increased in rats acutely treated with orogastric nicotine; conversely, viability was decreased in chronically treated rats. We conclude that acute nicotine exposure diminishes, whereas chronic nicotine exposure enhances, the effect of luminal acidity on mucosal surface cell intracellular pH and cell viability. These divergent effects correlate inversely with mucus gel thickness, suggesting that the mucus gel layer is an important component of the gastric mucosal barrier. PMID- 8496836 TI - In vitro effects of long-chain acylcarnitines on the permeability, transepithelial electrical resistance and morphology of rat colonic mucosa. AB - Absorption-enhancing properties of the long-chain acylcarnitines (C12-C18) were examined in vitro utilizing a modified Sweetana-Grass diffusion cell system. Transepithelial electrical resistance (TEER) and drug permeability (P) of rat colonic mucosa were used as parameters to determine the potency, selectivity and reversibility of acylcarnitine-enhancing effects. All long-chain acylcarnitines induced a rapid, concentration-dependent decrease in mucosal TEER. The minimum or threshold concentration (Ct) which produced a rapid decrease in mucosal TEER was determined for each acylcarnitine. Tissues treated with either palmitoyl or lauroyl carnitine at their Ct showed significantly better recovery of TEER after removal of the enhancers from the diffusion cells as compared to the other long chain acylcarnitines. In addition, palmitoyl and lauroyl carnitine treatment significantly enhanced the mucosal permeability to small, hydrophilic markers without adversely altering tissue morphology. Following enhancer replacement with buffer alone and the subsequent recovery of TEER, mucosal permeability was observed to return to near control levels. At higher concentrations of palmitoyl and lauroyl (5 x Ct), P increased nearly 2-fold over that observed at the Ct; however, epithelial barrier morphology was compromised. This study shows that colonic mucosal tissue mounted in modified Sweetana-Grass diffusion cells may be a useful model for examining the mechanism(s) of absorption enhancer activity. Moreover, the results present evidence that the long-chain acylcarnitines may enhance drug absorption via two different concentration-dependent pathways. PMID- 8496837 TI - Effects of adenosine agonists on ventilation during hypercapnia, hypoxia and hyperoxia in rhesus monkeys. AB - This study characterized in rhesus monkeys the effects of selected adenosine agonists on ventilation during normal atmospheric conditions and during conditions of hypercapnia, hypoxia and hyperoxia. In seated, unanesthetized monkeys prepared with a head plethysmograph, ventilation during exposure to air, CO2 (3, 4 and 5%) mixed in air (hypercapnia), 10% O2 mixed in N2 (hypoxia) and 100% O2 (hyperoxia) was measured during cumulative dosing with each drug. The nonselective (A1/A2) agonist, 5'-N-ethylcarboxamidadenosine (NECA), the peripherally active, A2-selective agonist, CGS 21680 [2 (carboxyethylphenylamino)adenosine-5'-carboxamide], and the A1-selective agonists, N6-cyclohexyladenosine and N6-cyclopentyladenosine, increased respiratory frequency (f), but had no significant effect on minute volume (VE) during exposure to air. The relative potencies for increasing f corresponded closely with their potencies for binding at A2 receptors. NECA and CGS 21680 increased f in a dose-dependent manner during exposure to 3% CO2, but proportional increases in f were less pronounced as the concentration of CO2 increased. NECA and CGS 21680 also increased f during hypoxia, but neither had a significant effect on f during subsequent hyperoxia. The highest dose of CHA and CPA decreased f below control values during exposure to 5% CO2 and decreased f and VE during hyperoxia. In contrast, the adenosine antagonist, caffeine, and the selective phosphodiesterase inhibitor, rolipram, increased f and VE under all conditions. During hypercapnia, the magnitude of the increases in f was similar at each concentration of CO2 studied. Caffeine and rolipram increased f and VE during hypoxia, and f and VE remained elevated during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496838 TI - Irreversible suppression of growth hormone-dependent cytochrome P450 2C11 in adult rats neonatally treated with monosodium glutamate. AB - Neonatal exposure to monosodium glutamate (MSG) permanently blocks growth hormone (GH) secretion, which results in the development of a well-defined syndrome characterized by stunted body growth, obesity and impaired drug metabolism. We have found that restoration of the normal masculine circulating profile of GH (i.e., six daily pulses) by use of an external pumping apparatus is ineffective in restoring the normal expression of hepatic cytochrome P450 2C11, a major GH dependent drug and steroid metabolizing enzyme that is eliminated by MSG treatment. Moreover, administering GH at two, four or seven plasma pulses per day with amplitudes ranging from physiologic to 7 times normal were similarly ineffective in restoring the expression (at both an activity and mRNA level) of the cytochrome. Additionally, multicytochrome P450-dependent hexobarbital hydroxylase was also unresponsive to GH administration in the MSG-treated rats. Because GH replacement was unable to correct the enzyme defects, our results suggest that the developmental abnormalities produced by neonatal MSG are not simply a result of a GH deficiency per se, but are due to an irreversible insensitivity of the target cell to GH. PMID- 8496839 TI - Relationship of thermal and chemical tolerance to transepithelial transport by cultured flounder renal epithelium. AB - We tested the effects of mild heat shock (MHS) on tolerance of epithelial transport processes to a chemical inhibitor and, reciprocally, chemical stress effects on tolerance to severe thermal stress. Flounder renal tubules were cultured as monolayers on native collagen for 12 to 14 days at 22 degrees C and mounted in Ussing chambers in which transepithelial electrical characteristics and unidirectional [35S]sulfate fluxes were measured. 2,4-dichlorophenoxyacetic acid (0.5 mM) lowered net active sulfate secretion 25% (93.6 +/- 7.64-69.0 +/- 9.08 nmol/cm2/hr); MHS (27 degrees C for 6 hr followed by 1.5 hr at 22 degrees C) prevented this inhibition (92.4 +/- 5.72 nmol/cm2/hr) and stimulated transport 30% (125.7 +/- 11.06 nmol/cm2/hr). Cycloheximide or actinomycin D prevented the enhancing and protective effects of MHS. Preincubation in 100 microM ZnCl2 for 6 hr at 22 degrees C followed by 1.5 hr in zinc-free medium (mild zinc stress) enhanced net sulfate flux, protected transport from severe heat stress (32 degrees C for 1.5 hr followed by 1.5 hr at 22 degrees C) and prevented 2,4 dichlorophenoxyacetic acid inhibition in a manner similar to MHS. Mild zinc shock induced heat shock protein synthesis the same as MHS. Cycloheximide prevented the mild zinc shock effect on transport. The data show that thermal or chemical stressors can independently induce tolerance of transepithelial transport to both thermal and chemical insults and that stress-induced "protection" is due to enhancement of normal function rather than prevention of damage. PMID- 8496840 TI - [Transcranial pulsed Doppler]. AB - Transcranial Doppler ultrasonography is the only non invasive examination enabling the reliable measurement of the blood flow velocity in the intracranial arterial trunks. However, it cannot be constantly perfect. It is fully realized in about 10% of the patient. Even incomplete it remains a useful complementary exploration in the management of the cerebral vascular disease. PMID- 8496841 TI - [Osteoid osteoma of the spine. Radiological study of 21 cases]. AB - Spinal osteoid osteomas are rare. We report 21 cases, that have been studied and treated since 1985. The tumor affects young people, who are less than 25 years old. The pain is the most common sign. Diagnosis is difficult, but can be made by radiology. X ray sometimes enables to suspect the diagnosis. Scintigraphy shows a focus hyperfixation more suggestive. Computed tomography enables the diagnosis by showing a bony lacuna surrounded by osteosclerosis. Moreover, computed tomography localizes very well the nidus of the osteoid osteoma, and guides the surgical treatment. Since computed tomography, other techniques like angiography and tomography are less used for diagnosis. PMID- 8496842 TI - [Scapular exostosis complicated by bursitis. Apropos of a case]. AB - We present one case of bursa formation secondary to a scapular osteochondroma. This rare condition can simulate, clinically and radiologically, a sarcomatous transformation. CT scan is helpful to demonstrate the scapular osteochondroma and the adjacent bursa. PMID- 8496843 TI - [Muscular myxoma. A case of myxoma of the psoas]. AB - Report about one case of rare tumor of the muscles (myxoma of the psoas muscles). Ultrasonographic, tomographic and arteriographic appearance. PMID- 8496844 TI - [Value of x-ray computed tomography and MRI in primary tumors of the ovary]. PMID- 8496845 TI - [Inflammatory and infectious lesions of the breast. Contribution of ultrasonography]. AB - Non puerperal abscess associated with periductal mastitis assumes increasing importance. US is an excellent tool for detection of an abscess cavity, which many have a variety of scanographic findings. Mammography may be difficult to perform properly because of pain and edema of the breast. PMID- 8496846 TI - [Ureteral endometriosis. Role of medical imaging]. AB - Three cases of ureteral endometriosis are reviewed. Computed tomography and magnetic resonance imaging show the mass which causes ureteral obstruction. The role of imaging modalities is discussed. PMID- 8496847 TI - [Magnetic resonance imaging of seminal vesicles. Normal and pathological aspects]. AB - We have studied the normal and pathological aspects of seminal vesicles by MRI with body coil by correlation between imaging and pathologic findings after radical surgery of 63 patients with urogenital carcinoma. On normal T2 weighted sequence, the ampulla of the was deferens visible in 71% of cases exhibited a nodular low signal intensity. Seminal vesicles demonstrated an hypersignal in 79%, a low signal intensity in 19% and an heterogeneous signal intensity in 2%. Overall accuracy for the diagnosis of invasion was 77%. MRI was not efficient for bladder carcinoma (sensitivity: 1; specificity: 82%) but it was always gross infiltration (superior to 5 mm) than for prostatic carcinoma (sensitivity: 40%; specificity: 67%). The numerous false positives (15 cases) were related to hypointense normal (8 cases) or fibrous (6 cases) seminal vesicles and one case of atrophy. The false negatives were related to small invasion. Only, the negative predictive value was good value (overall NPV: 96%; bladder carcinoma NPV: 1; prostatic carcinoma NPV: 89%). A normal bilateral hypersignal of seminal vesicles permit to eliminate a gross invasion. PMID- 8496848 TI - [Fast spin echo MRI techniques. Contrast characteristics and clinical potentials]. AB - Based on partial RF echo planar principles, Fast Spin Echo techniques (FSE) were implemented on high field systems. These methods produce image quality and contrast which resemble to conventional spin echo (SE) techniques. By reducing acquisition times by factors between 1.4 and 16 over SE methods, FSE allows for several imaging options usually prohibitive with conventional spin echo (SE) sequences. These include fast scans (especially breath-hold acquisitions); improved T2 contrast with longer TR intervals; increased spatial resolution with the use of larger image matrices and/or smaller fields of view; and 3D volume imaging with a 3D multislab FSE technique. Contrast features of FSE techniques are directly comparable to those of multiple echo SE sequences using the same echo spacing than FSE methods. However, essential contrast differences existing between the FSE sequences and their routine asymmetric dual SE counterpart can be identified. Decreased magnetic susceptibility effects and increased fat signal present within T2 weighted images compared to conventional dual SE images are due to the use of shorter echo spacings employed in FSE sequences. Off-resonance irradiation inherent to the use of a large number of radio frequency pulses in shown to results in dramatic magnetization contrast transfer effects in FSE images acquired in a multislice mode. PMID- 8496849 TI - [How to become a radiologist in Egypt]. PMID- 8496850 TI - Primary prevention of rheumatic disease. PMID- 8496851 TI - Fiddling while Rome burns: burn out, remission and disease activity measurements in ankylosing spondylitis. PMID- 8496852 TI - Cognitive and neurologic deficits in the MRL/lpr mouse: a clinicopathologic study. AB - OBJECTIVES: Determine if the MRL/lpr mouse develops neurological deficits and, if so, the pathologic basis for these deficits. Antiphospholipid antibodies (aPL) are associated with ischemic stroke, multiinfarct dementia, chorea, and cardiac valvular abnormalities. The MRL/lpr mouse develops high titer anticardioplin antibodies (aCL) suggesting that it may be used as a model for the neurological complications of aPL. METHODS: We undertook a prospective clinicopathologic study comparing the MRL/lpr mouse against its congenic strain, the MRL/+ mouse. We studied 15 MRL/pr and 15 MRL/lpr and 15 MRL/+ mice at 16 to 20 weeks and a group of 16 mice of each strain at 8 to 10 weeks. aCL and anti-DNA antibodies were measured by ELISA: Cognitive and neurological deficits were assessed by a water maze and a standardized rodent neurological examination. The brains and cardiac valves of the mice were then examined pathologically. RESULTS: The MRL/lpr mice had significantly elevated aCL at both ages. Cognitive and sensorimotor deficits were apparent at 16 weeks but no correlation could be found with aCL or anti-DNA titer. Even at 8 weeks the MRL/lpr mice performed poorer on the water maze when compared to their age matched congenic strain. No evidence of cerebral infarction was found but mononuclear infiltrates were found in the choroid plexus of all the MRL/lpr mice at both 10 and 20 weeks. No evidence of cardiac valve pathology was seen at 20 weeks. CONCLUSIONS: (1) The MRL/lpr mouse develops cognitive and neurologic deficits. The etiology of these deficits is not clear but may be related to early infiltration of the central nervous system with mononuclear cells. (2) Despite the elevated aCL, evidence of cerebral infarction or mitral valve abnormalities could not be found. PMID- 8496853 TI - Absence of rheumatoid arthritis in a rural Nigerian population. AB - A 2-stage population screening survey of 2,000 inhabitants of 2 rural townships in southern Nigeria was undertaken. No case of rheumatoid arthritis (RA) was discovered in those responding, although 3 cases of inflammatory polyarthritis were found. One of these individuals satisfied the modification of the American College of Rheumatology classification tree criteria that allows for missing radiographic data. Simultaneous monitoring, during a 4-month period, of the local health clinic serving the townships also failed to reveal a case of RA. Three (5.5%) of 55 individuals tested were positive for rheumatoid factor, a rate lower than in previous surveys of rural West African populations. Further immunogenetic investigation of that subsample from this population, using HLA oligonucleotide typing, suggested that HLA-DR4 was rare (1/55). Further, although HLA-DR1 was present in 7 (13%), 6 had the DRB1*0102 variant seen in black populations and not thought to be associated with RA. Our study confirmed the findings of others that rural African groups have extremely low rates of RA. In addition HLA genes containing the RA associated "shared epitope" are also relatively infrequent and might explain this reduction in RA prevalence. PMID- 8496854 TI - Human monoclonal rheumatoid factor derived from rheumatoid synovial cells monospecific for rabbit IgG. AB - Rheumatoid factors (RF) in rheumatoid arthritis (RA) are polyclonal autoantibodies directed against antigenic epitopes located in the Fc portion of the IgG molecule. Hybridoma technology has overcome the difficulty of their polyclonality, so that monoclonal RF (mRF) can be examined for their individual binding specificities and genetics. We isolated a monoclonal IgM RF secreting hybridoma (designated H4) from the rheumatoid synovial cells (RSC) of a patient with RA. H4 bound specifically with rabbit IgG (RIgG) and had no human IgG (HIgG) reactivity. By direct binding ELISA and absorption experiments, 6% of the RIgG reactive RSC RF in this patient with RA was monospecific for RIgG. H4 was tested against RIgG F(ab')2 and pFc' fragments, and bound only to the pFc' fragment (CH3 domain). Moreover, H4 mRF had high avidity for RIgG in a capture ELISA. Total RNA was extracted and the variable region heavy (VH) and light (VL) chain cDNA were amplified using polymerase chain reaction technology. Sequence analysis of the IgM RF VH and VL chain genes indicated usage of the VH26 germline gene (VhIII gene family) and a new V lambda germline gene. Our results suggest preferential use of restricted germline genes in the formation of autoantibodies in human autoimmune diseases. The pathological significance of RIgG specific RF is still unclear. However, this finding suggests that all RSC RF production may not necessarily be induced by autologous IgG. PMID- 8496855 TI - Gold therapy lowers serum interleukin 6 levels in rheumatoid arthritis. AB - OBJECTIVE: To determine the clinical utility and the effect of sodium aurothiomalate (GSTM) on serum interleukin 6 (IL-6) levels in patients with rheumatoid arthritis (RA). METHODS: Open prospective study of 50 patients with RA treated with GSTM. Serum IL-6 measured by bioassay. RESULTS: IL-6 showed correlations with Ritchie articular index, duration of morning stiffness and C reactive protein. GSTM significantly reduced IL-6 levels. CONCLUSIONS: IL-6 is a potentially useful additional indicator of disease activity in RA and is modulated by GSTM. PMID- 8496856 TI - Morphometric analysis of synovial membrane blood vessels in rheumatoid arthritis: associations with the immunohistologic features, synovial fluid cytokine levels and the clinical course. AB - The morphologic characteristics of the endothelial cells lining postcapillary venules are cytokine dependent and critical in facilitating the infiltration of mononuclear cells into synovial membrane in rheumatoid arthritis (RA). We determined the relationships between endothelial cell (EC) tallness, mononuclear cell infiltration and synovial fluid levels of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) at different stages of RA. EC tallness was greatest in synovial tissues obtained by needle biopsy of the knee joints from 18 patients with active RA who had never received disease modifying drugs (Group 1) (p = 0.000001 versus controls). EC tallness in tissues obtained from 18 patients with advanced disease undergoing knee arthroplasty (Group 2) was greater than controls (p = 0.001) only when vessels located in focal lymphoid aggregates were considered. Vascular proliferation was noted in both groups. Synovial fluid IL-6 levels were greatest in Group 1. IL-1 beta levels were greatest in Group 2. The total numbers of infiltrating mononuclear cells and the clinical measures of disease activity were similar in both groups. The differences in EC characteristics at different stages of RA suggest changing pathogenic mechanisms as disease progresses. Disease modifying antirheumatic drugs may contribute to the findings observed. PMID- 8496857 TI - Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice. AB - To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months. PMID- 8496858 TI - Combination therapy in rheumatoid arthritis--no benefit of addition of hydroxychloroquine to patients with a suboptimal response to intramuscular gold therapy. AB - OBJECTIVE: To determine if there is any advantage in adding hydroxychloroquine to intramuscular gold therapy in patients with rheumatoid arthritis (RA) with a suboptimal response to gold after 6 months of treatment. METHODS: Prospective double blind placebo controlled study at the Centre for Rheumatic Diseases, Glasgow Royal Infirmary and Gartnavel General Hospital, Glasgow. Patients--440 patients with RA began intramuscular gold therapy. One hundred forty-two patients with a suboptimal response at 6 months were randomized to receive additional treatment with hydroxychloroquine (400 mg/day) or placebo, and followed for a further 6 months. Outcome measures were erythrocyte sedimentation rate, C reactive protein, Ritchie articular index, grip strength, visual analog pain score, duration of morning stiffness, health assessment questionnaire, and rate of side effects. RESULTS: There was no difference in outcome in terms of efficacy or toxicity. CONCLUSION: There is no justification for using a combination of intramuscular gold and hydroxychloroquine in patients with RA with a partial response to gold. PMID- 8496859 TI - Fetal outcome of lupus pregnancy: a retrospective case-control study of the Hopkins Lupus Cohort. AB - OBJECTIVE: To determine the frequency of pregnancy loss, preterm birth, and therapeutic abortion in patients with systemic lupus erythematosus (SLE) versus controls. METHOD: The outcome of lupus pregnancy was determined in the largest retrospective case-control study to date, involving 203 patients with SLE with 481 pregnancies, 166 "best friends" with 356 pregnancies and 177 relatives with 566 pregnancies. RESULTS: Pregnancy loss (spontaneous abortion, miscarriage, or stillbirth) was more common in lupus pregnancies (21%) than in pregnancies in friends (14%, p = 0.01) or in relatives (8%, p < or = 0.0001) and was more common after the diagnosis of SLE than before (27 19%, p = 0.04). Preterm birth (< or = 36 weeks) was more common in lupus pregnancies (12%) than in pregnancies in friends (4%, p < or = 0.0001) or in relatives (4%, p < or = 0.0001) and was more common after the diagnosis of SLE than before (24 vs 6%, p < or = 0.0001). Preterm birth in lupus pregnancies after the diagnosis of SLE was associated with nonhigh school graduates (p = 0.001), Raynaud's phenomenon (p = 0.007), and hypertension requiring treatment (p = 0.01). CONCLUSION: We conclude that both pregnancy loss and preterm birth are significantly increased in lupus pregnancy versus control pregnancy and that these pregnancy outcomes are more common after the diagnosis of SLE. PMID- 8496860 TI - A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus. AB - SLEDAI, a disease activity index for systemic lupus erythematosus (SLE) has been validated against other such indices and its reliability has been shown by specialists in SLE. To assess its reliability among less experienced clinicians, we conducted a reliability study with 3 rheumatology trainees and 9 patients with SLE according to a Latin square design. SLEDAI easily distinguished between patients (p = 0.0009), and physician variability was not statistically significant (p = 0.27). Inter and intraobserver agreement were 78.7 and 98.0%, respectively. SLEDAI was thus shown to be a reliable instrument among less experienced observers for the assessment of disease activity in SLE. PMID- 8496861 TI - The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. AB - Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases. Patients taking hydroxychloroquine had 35-54% lower total triglyceride, VLDL triglyceride, LDL-triglyceride, HDL-triglyceride, VLDL-cholesterol, and apolipoprotein CIII levels (p < 0.03). These results are encouraging in that hydroxychloroquine, in addition to being useful for alleviating the primary symptoms of SLE, may also be useful for ameliorating the adverse effects of corticosteroid therapy on triglyceride-rich lipoprotein metabolism. PMID- 8496862 TI - Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York. AB - Using a case-control study design, patients with eosinophilia myalgia syndrome (EMS) who had used L-tryptophan (LT) were compared with LT users who did not develop EMS. Of the 113 case patients and 95 controls who had used a retail brand that could be traced to a bulk LT producer, all (100%) case-patients and 69 (73%) controls used LT brands that were traced to Showa Denko K.K. (lower 95% CL = 10.0). Among the users of LT produced by Showa Denko K.K., the risk of EMS was greater for persons who used LT produced after December 1, 1988 (OR = 25.8, [95% CL = 7.1, 101.4]). The risk of developing EMS increased with increased dosage of LT, increased age, and use of LT as a sleeping aid. These epidemiologic data support the hypothesis that the etiologic agent in EMS is a contaminant introduced into LT products during production. PMID- 8496863 TI - Methyl-alpha-D-mannopyranoside, mannooligosaccharides and yeast mannans inhibit development of rat adjuvant arthritis. AB - Methyl-alpha-D-mannopyranoside, mannooligosaccharides obtained by acetolysis of yeast mannan, and pure mannans isolated from the cell walls of pathogenic (Candida albicans) and nonpathogenic (Saccharomyces cerevisiae) yeasts were used for treatment of rat adjuvant arthritis. The arthritis was induced by the application of Freund's complete adjuvant into the tail region of rats. The mannose substances were injected into the arthritic rats intraperitonealy at different time intervals. Levels of serum albumin, changes in hindpaws swelling and radiographs were measured in infected rats as variables of the inflammation and destructive arthritic changes. While mannan from C. albicans inhibited both the inflammation and destructive arthritic changes, mannan from S. cerevisiae showed less effect. However, acetolysate of S. cerevisiae mannan as well as simple methyl-alpha-D-mannopyranoside inhibited both inflammation and destructive arthritic changes to a similar degree as mannan isolated from C. albicans. The effect, which is not dose dependent indicates its possible immunoregulatory mechanism. This is the first time a therapeutic effect of simple carbohydrates on rat adjuvant arthritis has been described. PMID- 8496864 TI - Rheumatic diseases and AIDS--is the association real? AB - There have been many reports of an association of certain musculoskeletal disorders especially Reiter's syndrome and psoriatic arthritis with human immunodeficiency virus (HIV) infection. A review of the first 1,100 HIV positive patients at the University of Cincinnati AIDS Clinic and Treatment Center has revealed 9 with psoriasis of whom 4 developed arthritis, 1 with Reiter's syndrome which predated HIV infection, 9 with nonspecific arthralgias, 7 with diffuse myalgias of whom 5 were AZT and one alpha-interferon related. Three patients with temporal arteritis/polymyalgia rheumatica, 2 of whom are biopsy proven, have been observed. The frequency distribution for race, age, sex for this population was contrasted to that expected. The only increased frequencies were in psoriatic arthritis with 4 cases observed and 0.73 expected and in temporal arteritis/polymyalgia rheumatica with 3 cases observed and 0.3 expected. Whether there is a coincidental or real increase is an important question requiring prospective, epidemiological studies to help determine if the differences reported are demographic or genetic. PMID- 8496865 TI - The clinical spectrum of the arthropathy associated with hidradenitis suppurativa and acne conglobata. AB - Patients with hidradenitis suppurativa/acne conglobata attending a university medical center were evaluated for the presence of an associated arthritis. Of 44 subjects, 21 had objective evidence of inflammatory arthropathy. Of these 21, all adults, 11 were women and 17 black Americans; clinically, 18 had peripheral arthritis, 15 axial arthropathy and 12 both. Clinical and laboratory findings were characteristic of those seen in other seronegative spondyloarthropathies, except for lack of association with HLA-B27. PMID- 8496866 TI - The natural history of ankylosing spondylitis. Does it burn out? AB - Initially, 1,492 patients with ankylosing spondylitis (AS) were assessed by a new disease activity index. This addressed the degree of pain, severity and overall disease activity (scale 3-26). As expected, there was a normal distribution with a median of 12. Sixty-five patients, selected from the extremes of the disease activity scale, (< 5, > 22), were prospectively followed over a 2-year period: 30 with high activity mean score 24.1 (SD 1.2) and 35 with low mean score 3.4 (SD 0.5). At followup, subjects were assessed with this new index and a validated functional index. Although at followup the high activity mean score was significantly reduced to 21.1 (p < 0.001) and the low activity mean score was significantly increased to 6.1 (p = 0.002), the majority of the patients had remained in their original quartiles i.e., 63 and 77%, respectively. Disease status at followup was independent of disease duration; i.e., high activity group mean 27.1 (SD 5.3) and remission group 26.9 (SD 13.77) years, respectively (NS). When the 2 disease indices were compared, an excellent correlation existed: r = 0.788, p < 0.001. Our data suggest (1) < 1% of patients with AS who present to a rheumatologist enter longterm remission ("burn out"). (2) Some 20% of patients in remission will develop active disease 2 years later. (3) The prognosis over 2 years for those with active disease is poor. PMID- 8496867 TI - Elevated metalloproteinase and tissue inhibitor of metalloproteinase mRNA in human osteoarthritic synovia. AB - The levels of metalloproteases and inhibitor expression in synovial membranes were measured by analyzing mRNA of collagenase, stromelysin, and tissue inhibitor of metalloproteinase (TIMP-1) in this tissue from 20 healthy persons and 20 patients with osteoarthritis (OA). Our results indicated that while most of the normal synovia expressed TIMP-1 mRNA at low levels, very few expressed metalloproteinase mRNA. In contrast 40% of patients with OA expressed a moderate level of collagenase compared to 55 and 80% cases with considerably elevated stromelysin and TIMP-1 mRNA, respectively. The mRNA expression of collagenase (p < 0.032), stromelysin (p < 0.0001) and TIMP-1 (p < 0.008) was significantly higher in OA than in normals. The greater abundance of stromelysin mRNA relative to collagenase indicates differential regulation of the 2 genes. We also demonstrated an association of IL-1 with metalloproteinase gene expression. PMID- 8496868 TI - Relationships between social background and medical care in osteoarthritis. AB - Arthritis is relatively more prevalent among those of low socioeconomic status and it is important that this group have access to good arthritis care. In our study looking at relationships between socioeconomic status and medical care, histories were obtained from a convenience sample of 110 community living elderly persons of varying social backgrounds who had symptomatic osteoarthritis (OA) of the hip and/or knee. Almost all subjects had seen a physician at some time for their OA, and low income and black subjects were twice as likely to be currently receiving OA care as others. However, in looking at instruction and monitoring in relation to therapeutic joint exercises as a qualitative aspect of medical care, subjects who had both above mean OA impairment and more than a high school education were found to have received much more comprehensive care than any other subgroup. PMID- 8496869 TI - Habitual physical activity is not associated with knee osteoarthritis: the Framingham Study. AB - We evaluated the potential risk factor by examining levels of habitual physical activity during middle age, and knee osteoarthritis (OA) in later years in the Framingham Cohort. Weight-bearing knee radiographs were obtained during the 18th biennial examination (1983-85), when the 1,415 subjects had a mean age of 73 years. Cohort members had been asked at 1954-57 and 1971-73 about the number of hours spent daily at various levels of physical activity, ranging from sedentary to heavy activity. Physical capacity measures, such as forced expiratory volume in one second and resting pulse rate, were also examined for association with OA. In the cohort, 97/589 men and 154/826 women had OA. We found no association between habitual physical activity and knee OA after adjusting for age, body mass index, knee injury, smoking and education. In the highest quartile of habitual physical activity compared to the least active, the aOR for men was 1.34 (95% CI: 0.66, 2.74) and for women was 1.09 (95% CI: 0.63, 1.90). There was no increase in the risk of knee OA with increasing physical activity in either men or women. Physical capacity measures were also unassociated with OA. Of interest, men with high levels of habitual physical activity had significantly elevated rates of asymptomatic osteophytes, [aOR = 2.14, (95% CI: 1.01, 4.54)], suggesting that habitual physical activity may influence development of osteophytes but not of more severe or symptomatic knee OA. In sum, habitual physical activity does not increase the risk of knee OA for men or women. PMID- 8496870 TI - The prevalence of chronic widespread pain in the general population. AB - OBJECTIVE: To establish the prevalence of chronic widespread pain and associated symptoms in a general population sample. METHODS: Cross sectional postal survey of 2,034 adults in the north of England. RESULTS: The point prevalence of chronic widespread pain was 11.2%. The symptom was strongly associated with other somatic complaints and with measures of depression and anxiety. CONCLUSION: In the general population, this cardinal symptom of fibromyalgia is common and identifies a group who are more likely also to report symptoms of fatigue and depression. PMID- 8496871 TI - Tophaceous gout in patients with renal transplants treated with cyclosporine A. AB - Hyperuricemia and gout have been associated with cyclosporine A (CyA) therapy in transplant recipients. We describe 4 patients who developed severe tophaceous gout after renal transplantation. All of the patients received CyA, prednisone, and diuretic therapy. Three had episodes of allograft rejection. No patient had the diagnosis of gout before transplantation. All developed tophi within 5 years of the first attack of gout. Management of these patients has been difficult due to renal insufficiency, drug interactions and toxicity. Clinicians should be aware that tophaceous gout can occur rapidly in CyA treated transplant recipients. PMID- 8496872 TI - Tophaceous gout in young patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) and gout have been associated infrequently. We describe 3 young adults with SLE who developed tophaceous gout relatively early in the course of their disease. All were underexcretors of uric acid but were studied after the development of renal disease; 2 were treated with diuretics. In 2 cases, gout became obvious while lupus was quiescent. PMID- 8496873 TI - Adenohypophyseal and sex hormones in pediatric rheumatic diseases. AB - Studies in adults with systemic lupus erythematosus (SLE) have shown normal estrogen and lowered androgen levels in serum and abnormal metabolism of estrogen. In our prospective study we tested the hypothesis that one or more of the following factors account for the increased incidence of SLE and pauciarticular juvenile rheumatoid arthritis (JRA) in females: (a) increased estrogen; (b) decreased androgen and (c) increased estrogen receptor in the peripheral blood mononuclear cells (PBMC). Serum and PBMC were collected from 51 healthy children (36 M: 20 F), 17 with JRA (all female) and 37 with SLE (11 M: 26 F). Estrogen receptor was measured in cytosol from PBMC using monoclonal antibody to estrogen receptor and solid phase enzyme immune assay. Serum levels of estrogen, androgen, prolactin, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured using standard radioimmunoassay. There were no significant differences in serum levels of estrogen and prolactin between healthy children and patients. Free androgen was lower in postpubertal boys and girls with SLE compared to healthy children. FSH and LH levels were higher in postpubertal boys and girls with SLE compared to healthy individuals. This trend, while not reaching statistical significance, was supported by a higher percentage of female patients with SLE and abnormal serum levels of FSH (p = 0.001), LH (p = 0.004) and prolactin (p = 0.001). The results of these preliminary studies suggest that the role of prolactin, FSH and LH in rheumatic diseases deserves further study. PMID- 8496874 TI - Methotrexate therapy in childhood systemic lupus erythematosus. AB - We evaluated the therapeutic potential of methotrexate (MTX) in patients with systemic lupus erythematosus (SLE). Their serious disease ruled out further treatment with prednisone or prednisone plus cyclophosphamide. Low dose oral MTX (5-10 mg/week) was added to the therapy (prednisone or prednisone plus cyclophosphamide) of 10 selected patients with SLE. Eight of them showed marked improvement and we were able to taper prednisone and completely discontinue cyclophosphamide therapy. Our results suggest that the use of oral MTX in low, weekly doses can be useful as adjunctive therapy for selected cases of childhood SLE. PMID- 8496875 TI - Detection of antibodies to the recombinant P39 protein of Borrelia burgdorferi using enzyme immunoassay and immunoblotting. AB - The diagnostic value of serologic tests using the recombinant P39 protein of Borrelia burgdorferi was compared with that of tests prepared from a whole spirochete antigen source. Immunoassays (ELISA and Western blot) prepared from either the recombinant protein or whole spirochetes were evaluated using a test panel comprised of 2 sera groups, one obtained from patients with clinically diagnosed Lyme disease, the other from individuals with no indication of past or current infection with B. burgdorferi. Results obtained indicate that ELISA screening tests relying on the recombinant protein are less sensitive than ELISA tests using whole spirochete antigen preparations. Western blot tests based on the P39 protein were more specific than P39 ELISA yielding no false positive or indeterminate results. These findings suggest that the P39 protein may prove valuable for confirmation testing for Lyme disease. PMID- 8496876 TI - Positive serology for Lyme borreliosis in patients with juvenile rheumatoid arthritis in a Lyme borreliosis endemic area: analysis by immunoblot. AB - Juvenile rheumatoid arthritis (JRA) and the arthritis of Lyme borreliosis in children can mimic each other. As false positive reactions are frequent in ELISA for Lyme borreliosis, they cannot be used reliably to make the distinction. Ninety-nine children diagnosed as having JRA at a children's hospital in an endemic area were evaluated by ELISA and immunoblot for antibodies to Borrelia burgdorferi. Sera from 9% were positive by ELISA, 5 of which showed bands on immunoblot. None met criteria for positive immunoblot. The antigenic basis of false positive ELISA was most frequently a reactivity to both 21 and 41 kDa. Analysis by immunoblot can help to definitively exclude Lyme borreliosis in children presenting with JRA in an endemic area. PMID- 8496877 TI - Inflammatory arthropathies in children with chromosomal abnormalities. AB - There are few observations of inflammatory synovitis in association with specific chromosomal abnormalities in children or adults. We review the genetic and rheumatic disease literature and describe the clinical, radiologic and pathologic features of a 14-year-old boy with trisomy 5q, terminal 2p deletion, developmental delay, and a 5-year course of a polyarticular, symmetrical arthropathy similar to juvenile rheumatoid arthritis. He was treated with multiple nonsteroidal antiinflammatory drugs, intramuscular gold, and oral methotrexate, but developed iridocyclitis, joint space narrowing with erosions, and multiple flexion contractures; disease progression slowed after addition of chlorambucil. The frequency and manner of association of genetic disorders with inflammatory arthropathies is presently unknown. Additionally, children with 2 major disabilities often require aggressive medical intervention to maximize their potential for adult independence. PMID- 8496878 TI - Lupoid sclerosis with antiphospholipid and antimyelin antibodies. AB - Lupoid sclerosis is a rare syndrome associating clinical symptoms of multiple sclerosis (MS), positive false tests for syphilis and positive tests for antinuclear and anticardiolipin antibodies. In a patient with lupoid sclerosis, antimyelin antibodies were detected by indirect immunofluorescence on human sciatic nerve sections. These antibodies were not found in the serum of control patients with MS nor in sera of patients with antiphospholipid autoantibodies and focal ischemic neurologic disease. The presence of such antimyelin antibodies may contribute to the underlying physiopathological mechanism of this syndrome. PMID- 8496879 TI - High dose methylprednisolone for retroorbital Wegener's granulomatosis. AB - Wegener's granulomatosis (WG) is frequently associated with retroorbital involvement, which typically responds slowly to the standard therapy of oral corticosteroids and cytotoxic agents. We describe the case of a 61-year-old man with WG, who developed marked retroorbital granulomatous inflammatory tissue and experienced a dramatic clinical and radiographic response to the administration of high dose intravenous (iv) methylprednisolone. We believe that high dose iv methylprednisolone may have distinct advantages over standard therapies in the treatment of retroorbital WG. PMID- 8496880 TI - Possible efficacy of hydroxychloroquine on accelerated nodulosis during methotrexate therapy for rheumatoid arthritis. PMID- 8496881 TI - Polymyalgia rheumatica and seronegative rheumatoid arthritis: some considerations based on a northern Italian population. PMID- 8496882 TI - Spondylitis due to group G. Streptococcus. PMID- 8496883 TI - Can methotrexate reduce the renal toxicity of parenteral gold? PMID- 8496884 TI - Acyclovir in rheumatoid arthritis. PMID- 8496885 TI - The efficacy of biphenylacetic acid 3% gel (Felbinac) in rheumatoid arthritis. PMID- 8496886 TI - Aseptic meningitis and focal central nervous system involvement in a case of adult onset Still's disease. PMID- 8496887 TI - Calcified synovial cyst of a zygapophyseal joint. PMID- 8496888 TI - Changes in kidney function and faecal excretion of water and electrolytes with sodium chloride loading in sheep. AB - The renal and faecal routes of water and electrolyte excretion in sheep were compared and changes in kidney function assessed when similar amounts of sodium chloride (NaCl) were dosed in free and fixed ratios in water. Sheep (n = 6) either had free access to fresh drinking water (control phase) or 0.9% saline drinking water, or NaCl was dosed intraruminally with free access to fresh drinking water. In the final phase of the investigation, sheep were dosed intraruminally with NaCl while water intake was restricted. Variables monitored included fresh or saline water intake, water, sodium and potassium loss via the urine and faeces, glomerular filtration rate (GFR), fractional excretions of sodium (FENa) and potassium (FEK) and solute free water clearance (CH2O). Results indicated that where NaCl intake was high, sodium excretion via the urine was of far greater importance than that via the faeces and that changes in kidney function which occurred in order to excrete excess sodium, included increases in GFR and FENa, and declines in FEK and CH2O. Where significant differences were obtained in variables between the phases of high salt intake, these were attributed to differences in sodium absorption from the gastrointestinal tract. It was concluded that when NaCl intake is high, sodium homeostasis is chiefly maintained by increasing the amount of sodium made available to the nephron tubule (increased GFR), by decreased tubular reabsorption of this sodium and by increasing solute free water reabsorption. PMID- 8496889 TI - Two very small viruses--a presumptive identification. PMID- 8496890 TI - Bone healing following two methods of non-rigid tibial osteotomy repair in the dog. AB - Bone healing was assessed after stabilisation of transverse tibial osteotomies in adult Beagles (n = 6) with intramedullary pins, in conjunction with modified Mennen clamp-on plates to counteract rotation. Post-operative return to full limb function was compared to that after use of a two-pin, uniplanar (Type I) external skeletal fixator and an intramedullary pin combination (n = 6). Additional external splinting was not used. The dogs were graded weekly after exercise, according to a functional performance grading scale. All of the clamp-on plates were well tolerated. Bony periosteal callus incorporated the crimp arms and the mean time required for full limb function was 7 weeks. The clinical performance of the dogs, with the external skeletal fixators and intramedullary pins, was consistently lower during the initial 4 weeks. Soft tissue swellings with pin tract drainage occurred, but resolved following removal of the transcortical fixation pins. These dogs returned to full limb function with bony bridging callus after 8 to 9 weeks. Quantitative assessment of the bone activity, using sequential scintigraphy at weekly intervals, suggested consolidation of the callus 6 weeks after the operation for the clamp-on plate and pin combination, and at 7 weeks for the external skeletal fixator and pin combination. PMID- 8496891 TI - Efficacy of moxidectin against internal parasites of sheep. AB - The efficacy of injectable and oral formulations of moxidectin, at a dosage of 0.2 mg kg -1 live mass was evaluated by the non-parametric method (NPM) against the most common internal parasites of sheep in 9 trials involving a total of 201 sheep. Both formulations obtained an A classification (more than 80% effective in more than 80% of the treated animals) against the third (L3) and fourth (L4) larval and adult stages of Haemonchus contortus, Teladorsagia circumcineta, Trichostrongylus colubriformis, Gaigeria pachyscelis, Chabertia ovina, Oesophagostomum columbianum and Dictyocaulus filaria, and L3 Nematodirus spathiger. The injectable formulation was similarly effective against L4 Strongyloides papillosus and the oral formulation against L4 N. spathiger and adult S. papillosus and N. spathiger. In contrast, a B classification (more than 60% effective in more than 60% of the treated animals) was obtained by the oral formulation against L4 of S. papillosus and by the injectable formulation against L4 and adult N. spathigher. Both formulations were ineffective against L3 S. papillosus, and the oral formulation also against the adults of this species. PMID- 8496892 TI - The pattern of faecal egg output in lambs infected with a multiple resistant strain of Haemonchus contortus after treatment with albendazole. AB - Worm-free lambs (n = 6) were infected with 5,000 L3 of an ivermectin/benzimidazole/closantel resistant strain of Haemonchus contortus. On Day 21 post infection animals were allocated, according to worm egg counts, to 2 groups of 3 animals each and on Day 29 one group was treated with albendazole at 3.8 mg kg-1, while animals in the other group remained untreated as controls. All animals were slaughtered on Day 44 when the treated group was found to have 2,083 +/- 1,718 worms and the controls 2,783 +/- 633, a reduction of 25.2% in worm burdens. The pattern of egg output was monitored and it was found that 2 d after dosing, worm egg counts had been suppressed by 89% in the treated group; thereafter the egg counts increased, but never returned to the pretreatment levels and by Day 15 post treatment, they were still 41.1% lower in the treated group than in the controls. PMID- 8496893 TI - Selected biochemical parameters in captive mountain tortoises (Geochelone pardalis). AB - The concentrations of sodium, potassium, chloride, urea, creatinine, uric acid, total protein, albumin, inorganic phosphorous, calcium, magnesium, cholesterol, triglyceride, glucose, aspartate and alanine transaminases (AST and ALT), creatine kinase (CK), lactic acid dehydrogenase (LD), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) and total bilirubin in the serum of a captive population of the mountain tortoise (Geochelone pardalis) (n = 13) were determined. Results varied considerably, particularly for most enzymes such as AST (11-113 U/l,ALT (1-72 U/l), CK (12-242 U/l), LD (147-2641 U/l) and ALP (56 168 U/l). PMID- 8496894 TI - Serological survey for canine leptospirosis in the Pretoria area. AB - Canine serum samples (n = 400) from the Pretoria area were tested for Leptospira antibodies, using the microscopic agglutination test. The prevalence of antibodies (inconclusive and positive titres) was 1.5%. Reactions were only against Leptospira interrogans serovars tarassovi and pyrogens. Leptospirosis does not appear to be an important canine disease in the Pretoria area. PMID- 8496895 TI - Effect of a 72 hour fast on physiological stress indicators in feedlot cattle. AB - Feedlot oxen (n = 15) were herded and subjected to venepuncture on a daily basis for 2 weeks. Plasma glucose, lactate, free fatty acids, total lipids, total protein, cortisol, catecholamines, osmolarity and haematocrit were compared between Days 1 and 14. Plasma glucose concentration and haematocrit decreased significantly while total plasma lipid and free fatty acid concentrations increased significantly over the 14 d. Thereafter, food was withdrawn for 72 h from the experimental group (n = 10) and the same blood variables were compared in the control and the experimental groups. Plasma free fatty acid concentrations rose, while glucose concentrations declined in the experimental group during the fasting period. It is concluded that food deprivation for 72 h in cattle cannot be regarded as a major stressor. PMID- 8496896 TI - An outbreak of narasin poisoning in swine. AB - An outbreak of narasin poisoning in swine is described. Forty nine out of 108 lactating sows died over a period of one month after being fed a ration accidentally contaminated with narasin. Clinical signs included anorexia, respiratory distress, lethargy and posterior paresis, progressing to lateral recumbency and death. Necropsy examination in 3 pigs revealed extensive myocardial and skeletal muscle damage. Analysis of the feed confirmed the presence of high concentrations of narasin. PMID- 8496897 TI - Neospora caninum infection in three Labrador littermates. AB - Neospora caninum is a recently identified protozoan parasite which was previously confused with Toxoplasma gondii. Neosporosis in puppies commonly causes signs referable to parasitic encephalomyelitis and myositis. The parasite was identified in tissues from 3 9-week-old Labrador littermates which showed signs of progressive hind limb hyperextension and paralysis. The diagnosis was confirmed, utilising a specific avidin-biotin immunohistochemical technique. Attempts to treat the pups with clindamycin were unsuccessful. One case was additionally treated with immunosuppressive doses of corticosteroids, but showed no improvement. Two pups were euthanased and necropsied. The predominant lesions were polymyositis and multifocal encephalomyelitis. Large clusters of tachyzoites were seen in the myofibres and thick-walled parasitic tissue cysts were found in the grey and white matter of the brain and spinal cord. PMID- 8496898 TI - Nonsteroidal anti-inflammatory agents in the management of canine allergic pruritus. AB - Pruritus associated with allergic skin diseases is an important reason for consultation in canine medicine. The pathophysiology of pruritus is poorly understood in the dog, but histamine, leukotrienes, and prostaglandins appear to be important mediators. The medical management of allergic pruritus in dogs with nonsteroidal anti-inflammatory agents is discussed. Antihistamines, tricyclic antidepressants, and omega-3/omega-6 fatty acid-containing products are often useful, either as single agents, in combinations, or for reducing glucocorticoid requirements. PMID- 8496899 TI - Efficacy of moxidectin against a strain of Haemonchus contortus resistant to ivermectin, a benzimidazole and a salicylanilide. AB - The efficacy of moxidectin at 0.2 mg kg-1 live body mass against the multiple anthelmintic resistant White River Krtz strain of H. contortus was determined and compared to that of ivermectin, a benzimidazole, a salicylanilide and levamisole. Moxidectin and levamisole were effective against this strain of H. contortus and reduced the arithmetic mean burdens of this parasite in the sheep by 99.98% and 99.59%, respectively, while the efficacy of ivermectin, albendazole and closantel was only 29.1%, 33.75% and 78.3%, respectively. PMID- 8496900 TI - Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands. AB - Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives, or linear, 2,3,3a,4,5,9a hexahydro-1H-benz[f]indole derivatives; they have either cis or trans ring junctions, and many of the ligands are resolved. In order to have X-ray crystal coordinates for every structural type, two additional crystal structures were determined: 14a, the trans-(+-)-6-hydroxy-3-(n-propyl) angular derivative as the hydrochloride, and (+-)-1,2,2a,3,4,8b-hexahydro-8-methoxy-2-(2-propenyl) naphth[2,1- b]azetidine hydrochloride (16d). Several recently reported imidazoquinolinones with dopaminergic and serotonergic activities were also used in developing the models as were other known ligands which are conformationally constrained. A new method for determining intrinsic activity at the D2 receptor made consistent and reliable estimates of dopamine agonist, partial agonist, and antagonist activities available. The models explain these activities in terms of the 3-dimensional structural features of the ligands and their probable orientations at the D2 receptor site. They also explain why allyl and propyl analogs of some structures have very different affinities while affinities are quite similar for allyl and propyl analogs of other structures; at both receptors a particular orientation of the amine substituent in the binding site correlates with preference for allyl over propyl derivatives. Suggestions are made for enhancing selectivity at the 5-HT1A receptor or at the dopamine D2 receptor. An angular, cis, (3aR,9bS), 2-propyl, 9-hydroxy, 3-(n-propyl) analog should be selective for the 5-HT1A receptor. A linear, trans, (3aR,9aS), 7-hydroxy, 1-(2 propenyl) analog should be selective for the dopamine D2 receptor, and would be predicted to be an antagonist. PMID- 8496901 TI - Interaction of calcium channel antagonists with calcium: spectroscopic and modeling studies on diltiazem and its Ca2+ complex. AB - Using spectral techniques, the solution conformation of diltiazem was studied in acetonitrile with special reference to the effect of Ca2+ on the drug structure. Complete assignment of the proton resonances in the 1H-NMR spectrum of the drug was made using one-and two-dimensional spectral analyses. A two-dimensional 1H NOESY spectrum (in the phase-sensitive mode) was obtained to identify the interproton connectivities in the drug molecule. A molecular modeling program involving Monte Carlo simulation and energy minimization was employed to arrive at the structure of the drug. The program was run with and without the input of the interproton distances derived from the NOESY cross peaks. Both the protocols led to a structure of the drug which was generally similar to that reported from X-ray diffraction data on crystalline diltiazem hydrochloride (Kojic-Prodic, et al. Helv. Chim. Acta 1984, 67, 916-926). However, significant differences between the two structures were seen in the orientations of the substituent groups attached to the benzothiazepine ring. Substantial changes in the circular dichroic (CD) and 1H-NMR spectra of diltiazem were observed on addition of Ca2+ up to a mole ratio of 0.5 Ca2+ per drug. Relatively large changes were seen in 1H resonances of the N-methyl protons and the methylene protons attached to the heterocyclic nitrogen. Analysis of the binding isotherms from CD data at 22 +/- 1 degrees C indicated a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 140 microM. One-dimensional difference NOE and two dimensional NOESY spectra revealed interproton connectivities between two drug molecules that were compatible with the sandwich complex formation. The interproton distances derived from the volume integrals of the NOESY cross peaks were used as geometrical constraints in modeling the Ca(2+)-bound conformation of diltiazem. The minimum-energy conformation corresponded to the sandwich complex where Ca2+ was coordinated to three oxygens in each of the two drug molecules. Combined with our earlier data on the ability of diltiazem to translocate Ca2+ across the lipid bilayer in synthetic liposomes (Ananthanarayanan, V.S.; Taylor, L.; Pirritano, S.Biochem. Cell Biol. 1992, 70, 608-612), the structural data presented here point to a role for Ca2+ in the interaction of diltiazem with its membrane-bound receptor. PMID- 8496902 TI - Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists. AB - A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2 receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5 (disubstituted) positions were favored. 1,3, 7-Trimethyl-8-(3 chlorostyryl)xanthine was a moderately potent (Ki vs [3H]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[(3 carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5 dimethoxystyryl) xanthine was a potent (Ki = 24 nM) and very A2-selective (110 fold) adenosine antagonist. PMID- 8496903 TI - Novel acyclonucleotides: synthesis and antiviral activity of alkenylphosphonic acid derivatives of purines and a pyrimidine. AB - A series of phosphonoalkenyl and (phosphonoalkenyl)oxy derivatives of purines and a pyrimidine were synthesized. These compounds are the first reported acyclonucleotides which incorporate the alpha,beta-unsaturated phosphonic acid moiety as the phosphate mimic and include compounds in which the acyclic substituent is attached to N-9 of a purine or N-1 of a pyrimidine by either a nitrogen-carbon or a nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1 hydroxypyrimidine under Mitsunobu conditions. The novel acyclonucleotides were tested for activity against herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), visna virus, and human immunodeficiency virus type 1 (HIV-1). Guanine derivatives were moderately to extremely cytotoxic, but the adenines were less toxic to cells. At the concentrations tested, (Z)-isomers in the unbranched series had no activity against herpes viruses or HIV-1. (E)-9-[(4-Phosphonobut-3-enyl) oxy]adenine (7d) displayed selective activity against HIV-1, (E)-2,6-diamino-9-(4-phosphonobut-3 enyl) purine (9) showed selective antiretrovirus activity, and (E)-9-[2 (hydroxymethyl)-4-phosphonobut-3-enyl]adenine (7c) showed selective antiherpesvirus (VZV and CMV) activity. PMID- 8496904 TI - Synthesis and antitumor activity of isodoxorubicin analogues. AB - The synthesis and biological activity of the new 4-demethoxyanthracyclines 15, 22, and 23 are reported. They were obtained from synthetic 9-deacetyl-9 (hydroxymethyl)-4-demethoxydaunomycinone (isopropylidene derivative 9) and from 4 azido- or 4-amino-2,4,6-trideoxy-L- lyxo-hexoses. Anthracycline 22 (hydrochloride salt), the most active compound in the series, was slightly more potent than doxorubicin in vitro against three cell lines (L1210, HT29, A549). It was found to exhibit similar antitumor activity in vivo (iv route) against L1210 leukemia, but was less active than doxorubicin against three human tumors in a subrenal capsule assay LXF, A549, and HT29). PMID- 8496905 TI - Synthesis and analgesic effects of N-[3-[(hydroxyamino) carbonyl]-1-oxo-2(R) benzylpropyl]-L-isoleucyl-L-leucine, a new potent inhibitor of multiple neurotensin/neuromedin N degrading enzymes. AB - The synthesis of N-[3-[(hydroxyamino) carbonyl]-1-oxo-2(R)-benzylpropyl]-L isoleucyl-L-leucine (JMV-390-1, 6a), a multipeptidase inhibitor based on the C terminal sequence common to neurotensin (NT) and neuromedin N (NN), is described. This compound behaves as a full inhibitor of the major NT/NN degrading enzymes in vitro, e.g. endopeptidase 24.16, endopeptidase 24.15, endopeptidase 24.11, and leucine aminopeptidase (type IV-S), in the nanomolar range (IC50's from 30 to 60 nM). Compound 6a was found to increase endogenous recovery of NT and NN from slices of mice hypothalamus depolarized with potassium. In various assays commonly used to select analgesics, e.g. hot-plate test, tail-flick test, acetic acid-induced writhing test, in mice, compound 6a proved to be potent when intracerebroventricularly (icv) injected. The analgesic effects observed were totally (hot-plate test) or largely (tail-flick test) reversed by the opioid antagonist naltrexone. Furthermore, icv injection of compound 6a (10 micrograms/mouse) was found to significantly potentiate the hypothermic effects of NT or NN. PMID- 8496906 TI - Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position. AB - Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2' ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3 propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute to the bronchodilator action of 1- and 7-substituted xanthines. This study indicates that the substitutions with none or low polar functional groups at the 1-position could improve the selectivity and duration of the bronchodilator effects of xanthines. PMID- 8496907 TI - Aromatase inhibitors: synthesis, biological activity, and binding mode of azole type compounds. AB - The enantiomers of the potent nonsteroidal inhibitor of aromatase fadrozole hydrochloride 3 have been separated and their absolute configuration determined by X-ray crystallography. On the basis of a molecular modeling comparison of the active enantiomer 4 and one of the most potent steroidal inhibitors reported to date, (19R)-10-thiiranylestr-4-ene-3,17-dione, 7, a model describing the relative binding modes of the azole-type and steroidal inhibitors of aromatase at the active site of the enzyme is proposed. It is suggested that the cyanophenyl moiety present in the most active azole inhibitors partially mimics the steroid backbone of the natural substrate for aromatase, androst-4-ene-3,17-dione, 1. The synthesis and biological testing of novel analogues of 3 used to define the accessible and nonaccessible volumes to ligands in the model of the active site of aromatase are reported. PMID- 8496908 TI - Interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles. Highly potent, selective, and long-acting thromboxane A2 receptor antagonists. AB - A series of interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles (2) were prepared and evaluated for their thromboxane (TxA2) antagonistic activity in vitro and duration of action in vivo. Examination of the carboxyl side chain indicated that the interphenylene ring substitution pattern and, to a lesser extent, chain length were important factors in determining TxA2 antagonistic potency. For the carboxyl side chain, ortho substitution, a single methylene spacer between the interphenylene and oxabicycloheptane rings, and a propionic acid side-chain length were determined to be optimal. With respect to the oxazole side chain a wide range of amide substituents with diverse structures and lipophilicities were compatible with potent antagonistic activity. Finally, an acidic functional group on the alpha-chain and a hydrogen bond acceptor on the 4-position of the oxazole ring were critical for potent activity. From the analogs prepared 42 (BMS 180,291: [(+)-1S-(1 alpha, 2 alpha, 3 alpha, 4 alpha)-2-[[3-[4-[(n- pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2- yl]methyl]benzenepropanoic acid) was found to be a potent, selective, and orally active TxA2 antagonist with a long duration of action and has been selected as a candidate for clinical development. In human platelet-rich plasma, 42 inhibited arachidonic acid (800 microM) and U-46,-619 (10 microM) induced aggregation with I50 values of 7 and 21 nM, respectively. Radioligand binding studies of 42 with [3H]-SQ 29,548 showed a Kd value of 4.0 +/- 1.0 nM in human platelet membranes. Both in vitro and in vivo studies indicated 42 was devoid of direct agonistic activity. In vivo 42 (0.2 mg/kg, po) showed extended protection (T50 = 14.4 h) from U-46,619 (2 mg/kg, iv) induced death in mice, and a single oral dose of 42 (3 mg/kg) abolished U46,619-induced platelet aggregation ex vivo in African green monkeys for > 24 h. PMID- 8496909 TI - Mechanism-based inhibitors of prostaglandin omega-hydroxylase: (R)- and (S)-12 hydroxy-16-heptadecynoic acid and 2,2-dimethyl-12-hydroxy-16-heptadecynoic acid. AB - 12-Hydroxy-16-heptadecynoic acid has been shown to selectively inactivate cytochrome P450 4A4, a pulmonary cytochrome P450 enzyme that catalyzes the omega hydroxylation of prostaglandins [Muerhoff, A. S.; Williams, D. E.; Reich, N. O.; CaJacob, C. A.; Ortiz de Montellano, P. R.; Masters, B. S. S. J. Biol. Chem. 1989, 264, 749-756]. Potent, specific inhibitors of this enzyme are required to explore its physiological role. In a continuing effort to develop such agents, the two enantiomers of 12-hydroxy-16-heptadecynoic acid have been stereospecifically synthesized, their absolute stereochemistry confirmed, and the dependence of enzyme inactivation on absolute stereochemistry determined using cytochrome P450 4A4 purified from the lungs of pregnant rabbits. The 12S enantiomer is roughly twice as active (KI = 1.8 microM, t1/2 = 0.7 min) as the 12R enantiomer (KI = 3.6 microM, t1/2 = 0.8 min), but the chirality of the hydroxyl group is not a major determinant of the specificity for the prostaglandin omega-hydroxylase. The flexibility of the acyclic skeleton of the inhibitor may account for the relatively low enantiomeric discrimination. 2,2 Dimethyl-12-hydroxy-16-heptadecynoic acid, an analogue that cannot undergo beta oxidation, has also been synthesized as a potential in vivo inhibitor of the enzyme and has been shown to inactivate the purified enzyme with KI = 4.9 microM and t1/2 = 1.0 min. These acetylenic agents, particularly the dimethyl analog, are promising in vivo inhibitors of cytochrome P450 4A4. PMID- 8496910 TI - Novel heterocyclic analogues of the new potent class of calcium entry blockers: 1 [[4-(aminoalkoxy)phenyl]sulfonyl]indolizines. AB - Several heterocyclic analogues of the potent 1-[[4 (aminoalkoxy)phenyl]sulfonyl]indolizines were synthesized and evaluated for their antagonistic calcium activities in comparison with the 1-sulfonylindolizine SR 33557 and the usual calcium antagonist references verapamil, cis-(+)-diltiazem, and nifedipine. The bicyclic nine-membered rings were, in general, more potent than the bicyclic 10-membered or five-membered rings. Among the bicyclic nine membered rings, the indole nucleus appeared to be extremely favorable to support the calcium antagonistic activity. In particular, compound 36, with an IC50 value for the inhibition of [3H]nitrendipine equal to 0.072 nM, is among the most potent calcium antagonist known. This compound has been selected for clinical development. PMID- 8496911 TI - 2'-substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis. AB - A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1 beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-microM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents. PMID- 8496912 TI - Application of the hypersurface iterative projection method to bicyclic pyrazolidinone antibacterial agents. AB - Bicyclic pyrazolidinones are a class of synthetic antibacterial agents in which the beta-lactam ring is replaced by a five-membered ring. These compounds possess electronic and shape properties required for inhibiting penicillin-binding proteins essential for bacterial cell growth. A novel approach called the hypersurface iterative projection (HIP) method, which is based on three dimensional computer graphics, allows available structure-activity information to be extrapolated to new synthetic targets. By updating the data set as the SAR evolves, the computer graphics reveal regions of parameter space to explore for optimum activity and regions yet unexplored. A large substituent parameter database is used to propose appropriate substituents. For the bicyclic pyrazolidinones, lipophilicity and particularly electron-withdrawing properties of the 3-substituent are shown to correlate strongly with minimum inhibitory concentrations (MIC). Antibacterial potency is intimately related to the activating effect of 3-substituents on chemical reactivity. The HIP method succeeded in proposing the most potent member of the series prior to synthesis and also showed when all of parameter space was reasonably well explored to the extent the chemistry allowed. PMID- 8496913 TI - Structure-activity relationships for mitomycins. Application of the distance and charge analysis method. AB - Molecular orbital calculations based on coordinates from X-ray analysis have been performed for a set of 24 mitomycins, of which eight compounds have not been isolated so far. To prioritize the order of synthesis of these missing compounds, a new method named DISCA (distance and charge analysis) has been developed. DISCA screens correlations between spatial distribution of charge in molecules and their biological activity. The spatial distribution of charge is represented by several indexes in DISCA. LD50 and ED50 were used as measures of biological activity. DISCA has successfully extracted indexes which have significantly high correlation coefficients. The indexes with the highest correlation coefficient were common to both LD50 and ED50. By use of the correlation functions with high correlation coefficients DISCA has predicted that 9-epi-1a-N-demethylmitomycin D should have the best ED50 and a modest LD50 among the missing mitomycins. PMID- 8496914 TI - Long-chain-substituted uric acid and 5,6-diaminouracil derivatives as novel agents against free radical processes: synthesis and in vitro activity. AB - A new series of N-alkylated uric acids (2,6,8-purinetrione) and 5,6 diaminouracils (5,6-diamino-2,4-pyrimidinedione) were synthesized, and their activities against free radicals were evaluated. Long-chain derivatives of both series exhibited a large inhibitory activity against oxygen radical induced lipid peroxidation in bovine heart mitochondria (IC50 lower than 1 microM), compared to the reference antioxidants trolox C or alpha-tocopherol. This activity appeared related to (i) the ability of these compounds to reduce the stable radical 1,1 diphenyl-2-picrylhydrazyl and (ii) their lipophilicity estimated by log P determination. In order to study the scavenging mechanisms of diaminouracils and urate derivatives against lipid radicals, they were also tested against the azo initiated peroxidation of either methyl linoleate in organic solvents or a liposomal suspension of dilinoleoylphosphatidylcholine. Urate derivatives reacted moderately with lipid radicals and were slowly consumed, significantly affecting the propagation of the peroxidation. Diaminouracils strongly reduced the propagation rate. They were quickly consumed and were able to deactivate about 1 mol of lipid radical per mole of compound in organic solvent. Dodecyl urates and decyl- and dodecyldiaminouracils were chosen for further in vitro investigation and in vivo evaluation. PMID- 8496915 TI - Antitumor agents. 141. Synthesis and biological evaluation of novel thiocolchicine analogs: N-acyl-, N-aroyl-, and N-(substituted benzyl)deacetylthiocolchicines as potent cytotoxic and antimitotic compounds. AB - Three series of novel thiocolchicine analogs, N-acyl-, N-aroyl-, and N (substituted benzyl)-deacetylthiocolchicinoids, have been synthesized and evaluated for their cytotoxicity against various tumor cell lines, especially solid tumor cell lines, and for their inhibitory effects on tubulin polymerization in vitro. Most of these compounds showed strong inhibitory effects on tubulin polymerization comparable to that obtained with thiocolchicine and greater than that obtained with colchicine. Only compounds with a long side chain at the C(7) position, such as 22-24, did not inhibit tubulin polymerization. Several of the active N-aroyldeacetylthiocolchicine analogs had positive optical rotations, in contrast to the negative optical rotation observed with most colchicinoids. This property might be attributed to a reversal of biaryl configuration from the normal aS to aR. Therefore, the N-aroyl analogs were further evaluated by circular dichroism, which readily distinguishes between the aS and aR biaryl configurations. This latter technique demonstrated that the active N-aroyl analogs do have an aS configuration despite their positive optical rotations. However, comparison of 1H NMR and UV spectral data of N-(substituted benzyl)-deacetylthiocolchicines with those of corresponding N aroyldeacetylthiocolchicines suggested a different biaryl dihedral angle [even though these compounds have the same aS biaryl configuration]. The similar tubulin binding properties of these compounds suggest that a biaryl dihedral angle of 53 degrees is not essential for colchicinoid-tubulin interaction. The increased cytotoxicity of N-(substituted benzyl)deacetylthiocolchicines compared to the N-aroyldeacetylthiocolchicines may be attributed to different lipophilicity, drug uptake, or drug metabolism in the tumor cells. The side chain at the C(7) position affects inhibition of tubulin polymerization and the cytotoxic activity of colchicinoids as a function of its size and its contribution to lipophilicity. PMID- 8496916 TI - Synthesis and biological activity of spirocyclic benzopyran imidazolone potassium channel openers. AB - A series of novel spirocyclic benzopyran imidazolones were synthesized as rigid analogues of cromakalim. These compounds cause a dose-dependent membrane hyperpolarization of A10 rat aorta cells. This hyperpolarization was blocked by pretreatment with glyburide, indicating that the spirocyclic benzopyran imidazolones were acting by increasing the open probability of ATP-sensitive potassium channels in A10 cells. Representative compounds also showed potent in vivo activity as hypotensive agents in normotensive rats. Many of the compounds described are much more potent than cromakalim both in vitro and in vivo, with one of the most potent compounds being 2,3-dihydro-2,2-dimethyl-6-nitro-2' (propylamino)spiro[4H-1-benzopyran- 4,4'-[4H]imidazol]-5'(1'H)-one (5r). It is concluded that the N1' nitrogen of the imidazolone is an effective substitute for the carbonyl oxygen of cromakalim. The rigid spirocyclic ring fusion holds this nitrogen in an optimum orientation relative to the benzopyran ring. PMID- 8496917 TI - Bridged gamma-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors. AB - A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10 hexahydro-7,10- iminocyclohept[b]indole (5, Ki = 0.82 nM vs [3H]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies. The indole ring, as well as the benzoyl or isosteric benzisoxazole moiety, were essential for high affinity. Variations of the length of the side chains resulted in ligands having either selective affinity for the 5-HT2 receptor or a combination of 5-HT2 and D2 affinity. In vivo binding studies were performed on selected members in this series. The most potent member, 2-fluoro-11-[4-(4 fluorobenzoyl)butyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (36) had an ED50 of < 1 mg/kg at the 5-HT2 and D2 receptors following oral administration. PMID- 8496918 TI - Orally active water-soluble N,O-acyl transfer products of a beta,gamma bishydroxyl amide containing renin inhibitor. PMID- 8496919 TI - N-(arylalkyl)farnesylamines: new potent squalene synthetase inhibitors. PMID- 8496920 TI - (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S) WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. PMID- 8496921 TI - Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3 acylamino lactams. AB - A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3 (trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system. PMID- 8496922 TI - Synthesis and serotonergic activity of 5-(oxadiazolyl)tryptamines: potent agonists for 5-HT1D receptors. AB - The synthesis and 5-HT1D receptor activity of a novel series of 5 (oxadiazolyl)tryptamines is described. Modifications of the oxadiazole 3 substituent, length of the linking chain (n), and the amine substituents are explored and reveal a large binding pocket in the 5-HT1D receptor domain. Oxadiazole substituents such as benzyl are accommodated without loss of agonist potency or efficacy. The incorporation of polar functionality on a phenyl or benzyl spacer group results in a 10-fold increase in affinity and functional potency. Optimal 5-HT1D activity is observed when the heterocycle is conjugated with the indole and the benzyl sulfonamides 20t and 20u represent some of the most potent 5-HT1D agonists known. Replacement of O for S in the heterocycle leads to a further increase in potency. Deletion of oxadiazole N-2 does not reduce activity, suggesting the requirement for only one H-bond acceptor in this location. The selectivity of these compounds for 5-HT1D receptors over other serotonergic receptors is discussed. Sulfonamide 20t shows > or = 1000-fold selectivity for 5-HT1D over 5-HT2, 5-HT1C, and 5-HT3 receptors and 10-fold selectivity with respect to 5-HT1A receptors. The functional activity of this series of compounds is studied and demonstrates high 5-HT1D receptor potency and efficacy comparable to that of 5-HT. PMID- 8496923 TI - New mechanism-based inactivators of trypsin-like proteinases. Selective inactivation of urokinase by functionalized cyclopeptides incorporating a sulfoniomethyl-substituted m-aminobenzoic acid residue. AB - In order to obtain selective suicide substrates of trypsin-like proteases including plasminogen activators, plasmin, and thrombin, a series of cyclopeptides cyclo[Arg or Lys-aB(CH2X)-Gly4], in which a substituted o- or m aminobenzoyl group constitutes a latent electrophile, have been prepared. Treatment of the corresponding phenyl ethers cyclo[P1-aB(CH2OC6H5)-Gly4] with HBr/HOAc or R1R2S/TFA gives the bromides (X = Br) or the sulfonium salts (X = +SR1R2 with R1 = R2 = Me or R1 = Me and R2 = C6H5), respectively. These water soluble cyclopeptides behave as time-dependent inhibitors of bovine trypsin and human urokinase (u-PA) but have no effect on tissue plasminogen activator (t-PA) and no or poor effect on plasmin and thrombin. The compounds containing a m aminobenzoic acid residue are more efficient inactivators than their anthranilic analogues. The kinetic criteria expected for a suicide inhibition are met. A mechanism of inhibition involving the formation of a quinonimmonium methide intermediate is proposed. The activity of the inhibitors is very sensitive to the nature of the X benzylic substituent. An increased efficiency for the inactivation of human urokinase is observed with the sulfonium salts. The selectivity of the inactivation of u-PA compared to t-PA could be of therapeutical significance in controlling cell proliferation and invasion. PMID- 8496924 TI - A molecular dynamics study of the bis-intercalation complexes of echinomycin with d(ACGT)2 and d(TCGA)2: rationale for sequence-specific Hoogsteen base pairing. AB - The behavior of the complexes of echinomycin with the DNA tetramers d(ACGT)2 and d(TCGA)2, in which the terminal AT base pairs are in either a Hoogsteen or a Watson-Crick conformation, has been explored by molecular dynamics taking into account experimental data from NMR studies (Gao and Patel. Biochemistry 1988, 27, 1744-1751). The DNA binding specificity of echinomycin appears to be the result of a subtle balance between stabilizing and destabilizing forces. Among the former is a number of hydrogen bonds between the alanine residues of echinomycin and both the N3 and 2-amino groups of the guanine bases which decisively determine the strong affinity of the antibiotic for CpG steps. On the other hand, there appears to be an unfavorable dipolar interaction between the chromophores of the antibiotic and the CpG step. This electrostatic component of the stacking interactions also contributes to explaining the conformational preferences of the flanking sequences: upon Hoogsteen pairing, the dipole moment of an AT base pair is found to increase significantly and alter its relative orientation. In the d(ACGT)2:echinomycin complex, this arrangement helps to improve the stacking interactions with the quinoxaline-2-carboxamide system, but would lead to unfavorable dipolar interactions in the d(TCGA)2 complex. The bearing of these findings on the binding of echinomycin to several sequences as well as on the altered binding selectivity of other members of the quinoxaline family of antibiotics is also discussed. PMID- 8496925 TI - Modeling the anticancer action of some retinoid compounds by making use of the OASIS method. AB - The powerful OASIS (optimized approach based on structural indices set) approach is applied to the anticancer activity of a series of vitamin A analogs. The best three- and four-variable models obtained via the OASIS technique have correlation coefficients of 0.973 vs. 0.990 and standard deviations s2 = 0.11 and 0.05, respectively. The models incorporate the hydrophobicity factor log P, two geometric parameters (topological indices and/or 3-D steric ones), and the molecular dipole moment. For a set of 15 compounds studied here, the activity measured by ED50 was well correlated by models with approximately equal contribution of the through cell membrane transport and the geometric drug receptor correspondence while weak nonspecific electronic interaction was also found to play some role. Comparison to previous treatments of this data is given and extension to larger sets is discussed. PMID- 8496926 TI - Synthesis of 2'-deoxyuridine and 5-fluoro-2'-deoxyuridine derivatives and evaluation in antibody targeting studies. AB - Derivatives of 2'-deoxyuridine and of the anticancer agent 5-fluoro-2' deoxyuridine (FdUR) were linked indirectly via a human serum albumin carrier (HSA) to the murine antiosteosarcoma monoclonal antibody 791T/36. Starting from the 2'-deoxyuridines 1a and 1b, the new nucleosides containing 5'-succinamic acid 7 and 5'-maleamic acid 8 spacers were synthesized from the key intermediate 5' aminonucleoside 4, and the ribofuronamidobenzoic acid 13 from ribofuranuronic acid 10. These nucleosides were linked via their spacer functionality to HSA. High molar substitution ratios (MSR: moles of drug/mole of HSA) of 25-40 for these derivative-HSA conjugates were achieved. All derivatives were less cytotoxic than the parent drug against both antigen positive osteogenic sarcoma 791T and antigen negative bladder carcinoma T24 cell lines; no IC50 was achieved with any derivative against 791T cells. The fluorodeoxyuridine-HSA conjugates were then further linked via a stable thioether bond to the mouse monoclonal antibody 791T/36. The optimum fluorinated 5'-succinamic acid immunoconjugate exhibited an IC50 of 1 microM against 791T and T24 cells, slightly better than that of fluorodeoxyuridine. The unconjugated derivative 7 was much less cytotoxic than immunoconjugate, with an IC50 of 62 microM on T24 cells, and failed to reach 50% inhibition of 791T cell growth at 290 microM concentration. Derivative 7-HSA conjugate was 10-fold less cytotoxic than the immunoconjugate against both cell lines. Immunoconjugates synthesized with the other 5-fluoro derivatives were unable to effect 50% inhibition of growth of cell lines. Nonfluorinated derivatives and their HSA conjugates and immunoconjugates exhibited no cytotoxicity. PMID- 8496927 TI - A novel series of N-(1-aminoalkylidene)carboximidamides as potential hypoglycemic agents. AB - Nitrogen heterocyclic carboximidamides, such as linogliride, 1a, have been shown to possess significant hypoglycemic activity and have shown clinical efficacy as potential antidiabetic agents. We evaluated the biological significance of the heterocyclic ring A of general structure 1, which has always been maintained in this class of compounds, by preparing acyclic compounds of general structure 2. Preliminary in vivo biological testing, i.e., the glucose tolerance test in rats, indicates that a number of the specific acyclic carboximidamides prepared, 6a-kk, possessed significant hypoglycemic activity often comparable to, and in some cases better than, the activity noted for our model compound, 1a. These results suggest that the heterocyclic ring A of 1 is not essential for hypoglycemic activity for this class of compounds. PMID- 8496928 TI - Syntheses and biological activities of potent potassium channel openers derived from (+/-)-2-oxo-1-pyridin-3-yl-cyclohexanecarbothioic acid methylamide: new potassium channel openers. AB - The syntheses and biological activities of (+/-)-2-(cyanomethylene)-1-pyridin-3 ylcyclohexanecarbothioic++ + acid methylamide (6) and trans-(+/-)-2-(cyanomethyl) 1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (14) derived from (+/-)-2 oxo-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (4) are reported. Compounds were tested for antagonism of potassium-induced contraction of de endothelialized rat aorta. The effects of modification of 6 and 14 on in vitro K(+)-channel opening activity are presented. These new series of potassium channel openers so derived are best exemplified by (+/-)-2-[2 (phenylsulfanyl)ethylidene]-1-pyridin-3-ylcyclohexan ecarbothioic acid methylamide (13d, RP 66266) and trans-(+/-)-2-[2-[(phenylsulfonyl)amino]ethyl]-1 pyridin-3- ylcyclohexanecarbothioic acid methylamide (25a, RP 66784), which have IC90 values of 3 and 0.3 nM, respectively. The potency of the most active compounds indicates a possible interaction at an extra binding site. The compounds described herein are potential antihypertensive and antianginal agents. PMID- 8496929 TI - Dibenzoxepin derivatives: thromboxane A2 synthase inhibition and thromboxane A2 receptor antagonism combined in one molecule. AB - A new series of 6,11-dihydrodibenz[b,e]oxepin derivatives exerting both thromboxane synthase inhibitory (TXS-I) and thromboxane receptor antagonist (TXRA) activities is described. (-)-11-[(3-Pyridylmethyl)thio]-6,11 dihydrodibenz[b,e]oxepin -2- carboxylic acid [(-)-3] and (E)-11-[2-(3 pyridyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin+ ++-2- carboxylic acid methanesulfonate (11E) exhibited potent inhibitory effects on bovine platelet thromboxane synthase with IC50 values of 4.0 and 14 nM, respectively, and these derivatives also antagonized guinea pig platelet TXA2/PGH2 receptors with Ki values of 85 and 180 nM, respectively. Compound 11E exhibited the dual inhibitory activity in ex vivo experiments and demonstrated a significant protective effect in a rat acute renal failure model. PMID- 8496930 TI - Structure-activity relationship of N-[2-(dimethylamino)-6-[3-(5-methyl-4-phenyl 1H-imidazol-1-yl)propoxy] phenyl]-N'-pentylurea and analogues. Novel potent inhibitors of acyl-CoA:cholesterol O-acyltransferase with antiatherosclerotic activity. AB - We have discovered N-butyl-N'-[2-(dimethylamino)-6-[3-(4-phenyl-1H- imidazol-1 yl)propoxy]phenyl]urea (4), a novel, potent, and systemically bioavailable inhibitor of ACAT (acylCoA:cholesterol O-acyltransferase). The structure-activity relationships (SARs) of this lead compound 4 were investigated by systematic modification of four regions in the molecule. The compounds prepared in this study were tested for in vitro inhibitory activity toward both aortic and intestinal ACATs, and selected compounds were further tested for in vivo hypocholesterolemic activity. The studies not only resulted in the discovery of N [2-(dimethylamino)-6-[3-(5-methyl-4-phenyl-1H-imidazol-1-yl) propoxy]phenyl]-N' pentylurea (24), with potent activity and moderate plasma level after oral administration, but also revealed the SAR in each modified region. Four compounds (4, 13, 14, 24) were further selected for testing of in vivo antiatherosclerotic activity; 4, 13, and 24 reduced atherosclerotic plaque development to 38-45% of the control value in terms of area, while 14 did not have a significant antiatherosclerotic effect. PMID- 8496931 TI - Structure-activity relationship of a series of phenylureas linked to 4 phenylimidazole. Novel potent inhibitors of acyl-CoA:cholesterol O acyltransferase with antiatherosclerotic activity. 2. AB - In our continuing search to find systemically bioavailable ACAT (acyl CoA:cholesterol O-acyltransferase) inhibitors with more potent antiatherosclerotic effect than N-[2-(dimethylamino)-6-[3-(5-methyl-4-phenyl-1H imidazol-1-yl)propoxy] phenyl]-N'-pentylurea (3), a series of phenylureas linked to 4-phenylimidazole were synthesized and evaluated for in vitro inhibitory activity toward both aortic and intestinal ACATs, and for in vivo hypocholesterolemic activity. The structure-activity relationships (SARs) were studied by strategic modification of five regions in the molecule of 3, i.e., by introducing functional groups or exchanging carbon atoms for heteroatoms. The SAR studies allowed us to select optimum substituents in the five regions, as follows. (1) Dimethylamino was convertible into nitro, methyl, ethyl, propyl, isopropyl, and chloro. On the basis of preliminary pharmacokinetic studies, the methyl group in the ortho-position of the phenylurea was selected. (2) Butyl, pentyl, isopentyl, and neopentyl were better substituents in the urea moiety. (3) Propoxy was the optimal moiety in the bridging portion. (4) Proton, methyl, ethyl, isopropyl, hydroxymethyl, and chloro were better substituents at the 5 position of the imidazole moiety. (5) An unsubstituted phenyl ring was selected as the phenyl group of phenylimidazole. The subsequent comparison studies of compounds containing various combinations of the optimum substituents in each region resulted in the selection of two compounds (67, 68) for further pharmacological and toxicological testing. These compounds were orally bioavailable, and possessed potent in vitro aortic ACAT inhibitory activity (IC50 = 0.16 and 0.012 microM, respectively) and in vivo cholesterol lowering effect (46% and 52% at 1 mg/kg po, respectively). In particular, 68 was 10-fold more potent in the in vitro aortic ACAT assay and 5-fold more potent with respect to hypocholesterolemic activity in vivo than 3. PMID- 8496932 TI - Inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). 2. Modification of fatty acid anilide ACAT inhibitors: bioisosteric replacement of the amide bond. AB - In order to further define the structural features necessary for potent inhibition of acyl-coenzyme A:cholesterol acyltransferase (ACAT) in vitro and cholesterol lowering in vivo, systematic study of bioisosteric replacements for the amide bond in our previously identified series of fatty acid anilide ACAT inhibitors was undertaken. Only replacement of amide bonds with isosterases having both hydrogen bond donor and acceptor functionalities yielded compounds retaining ACAT inhibitory activity. Replacement of the amide bond with the urea bioisostere yielded compounds that were potent ACAT inhibitors in vitro and efficacious hypocholesterolemic agents in vivo. Examination of the structure activity relationships in the phenyl ring and alkyl portion of the N-phenyl-N' alkylureas revealed that 2,6-diisopropyl substitution was optimal in the phenyl ring. When the 2,6-diisopropyl moiety was kept constant, potency in vitro and in vivo was maintained with straight and branched alkyl groups from 6 to 18 carbons in length. PMID- 8496933 TI - A new candidate for an anti-HIV-1 agent: modified cyclodextrin sulfate (mCDS71). PMID- 8496934 TI - L-beta-(2S,4S)- and L-alpha-(2S,4R)-dioxolanyl nucleosides as potential anti-HIV agents: asymmetric synthesis and structure-activity relationships. AB - In order to study the structure-activity relationships of L-(2S,4S)- and L (2S,4R)-dioxolanyl nucleoside as potential anti-HIV agents, various enantiomerically pure L-(2S,4S)- and (2S,4R)-dioxolanylpyrimidine and -purine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells. The enantiomerically pure key intermediate 8 has been synthesized in six steps from 1,6-anhydro-beta-L-gulose (2), and compound 8 was condensed with 5-substituted pyrimidines, 6-chloropurine, and 2,6 disubstituted purine to obtain various dioxolanylpyrimidine and -purine nucleosides, respectively. Among the compound synthesized, 5-fluorocytosine derivative 29 was found to exhibit the most potent anti-HIV activity (EC50 = 0.0012 microM) although it was toxic (IC50 = 10.0 microM). The order of anti-HIV potency of pyrimidine analogues was as follows: 5-fluorocytosine (beta-isomer) > cytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-iodocytosine (beta isomer) > cytosine (alpha-isomer) > 5-bromocytosine (beta-isomer) > thymine (beta isomer) > 5-methylcytosine (alpha-isomer) > 5-iodocytosine (alpha-isomer) > 5 chlorocytosine (beta-isomer). The anti-HIV potency of purine analogues was found to be in the following decreasing order: 2,6-diaminopurine (beta-isomer) > 2 chloroadenine (alpha-isomer) > 2-fluoroadenine (beta-isomer) > adenine (beta isomer) > 2-amino-6-chloropurine (alpha-isomer) > 2-amino-6-chloropurine (beta isomer) > guanine (beta-isomer) > 2-fluoroadenine (alpha-isomer) > adenine (alpha isomer) > 2,6-diaminopurine (alpha-isomer) > N6-methyladenine (beta-isomer). It is interesting to note that the alpha-5-fluorocytosine analogue exhibited an excellent anti-HIV activity (EC50 = 0.063 microM) without cytotoxicity up to 100 microM in PBM cell. PMID- 8496935 TI - Antitumor agents. 139. Synthesis and biological evaluation of thiocolchicine analogs 5,6-dihydro-6(S)-(acyloxy)- and 5,6-dihydro-6(S)-[(aroyloxy)methyl]-1,2,3 trimethoxy-9-(methylthio)-8H- cyclohepta[a]naphthalen-8-ones as novel cytotoxic and antimitotic agents. AB - A series of novel thiocolchicine analogs, 5,6-dihydro-6(S)-(acyloxy)-and 5,6 dihydro-6(S)-[(aroyloxy)-methyl]-1,2,3-trimethoxy-9-(methylthi o)-8H- cyclohepta[a]naphthalen-8-ones, possessing a six-membered ring B, have been synthesized and evaluated for their cytotoxicity against various tumor cell lines, including solid tumor cell lines, and for their interaction with tubulin. The configuration of the parent alcohol (compound 5) was established unequivocally as (aR,6S) by X-ray crystallographic analysis. The side chain at the C(6) position is in a pseudoaxial orientation. The optical properties and 1H NMR data indicated that these compounds have the same conformations in solution as in the solid state. Biological results showed that compounds (5, 6, 14, 15, 17, and 18) bearing a small side chain at C(6) demonstrate high potency in inhibiting tubulin polymerization and binding of radiolabeled colchicine to tubulin. The most cytotoxic compounds were 14, 15, 17, and 18, with good activity against several solid tumor cell lines. To explain the strong antitubulin activity of compound 5 (with an aR configured biaryl system in contrast to the aS configuration previously described for colchicinoids, allocolchicinoids, and steganacin) we speculate that a rapid atropisomerism equilibrium must exist for 5 and its active derivatives. This equilibrium would yield adequate amounts of aS configured conformers that interact, strongly with tubulin. Since the optically inactive 18 is also a potent inhibitor of tubulin, the configuration of the side chain of these six-membered ring B analogs cannot be essential for their binding to tubulin. Instead we propose that the size of ring B and of its side chain play important roles in tubulin binding activity by affecting the rotation of the rings A and C along their linking C-C bond axis. PMID- 8496936 TI - Synthesis and binding characteristics of potential SPECT imaging agents for sigma 1 and sigma-2 binding sites. AB - 2-, 3-, and 4-idophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4 dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma 1 and sigma 2 subtypes in vitro. sigma-1 binding affinity was determined by measuring competition with [3H]-(+)-pentazocine binding to guinea pig brain membranes while sigma 2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma 1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4 dichloro substituents of 1. In this series of compounds, Ki's at the sigma 1 site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (4). Ki's for sigma 2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma 2/sigma 1 ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma 1 sites; no such trend was observed at sigma 2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with 123I. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with Na123I in the presence of excess CH3CO3H furnished [123I]-2 and [123I]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [123I]-3 indicated up to 97% specific binding with guinea pig brain membranes. PMID- 8496937 TI - Synthesis of 2-imidazolidinylidenepropanedinitrile derivatives as stimulators of gastrointestinal motility. AB - Ranitidine (1), the histamine H2-receptor antagonist, has been previously reported to increase gastric emptying and gastric motility by inhibition of acetylcholinesterase (AChE) and enhancement of acetylcholine (ACh) release. In order to obtain potent gastroprokinetic agents, a new series of ranitidine derivatives (5-32) possessing a nitrogen atom instead of a sulfur atom (B) was synthesized and their AChE inhibitory activity and potentiating action on electrically evoked contractions of guinea pig ileum were evaluated. Modification of substituents R1 and R2 markedly influenced the activities. In particular, compound 19, (1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]-ethyl]-2- imidazolidinylidene)propanedinitrile fumarate, showed 20 and 100 times more potent AChE inhibitory activity and potentiating action on the ileal contraction, respectively, than ranitidine. Furthermore, compound 19 (KW-5092) enhanced gastrointestinal motility in anesthetized rabbits along with a negligible histamine H2-receptor blocking activity. PMID- 8496938 TI - Analogues of platelet activating factor. 8. Antagonists of PAF containing an aromatic ring linked to a pyridinium ring. AB - A series of platelet activating factor (PAF) antagonists containing a quaternary pyridinium ring connected through an amide, imide, or carbamate linkage to a substituted aromatic ring was prepared. Of these compounds, those containing a branched imide linkage of the form (CON-(COCH3)CH2, 37-51, and 59) generally showed excellent PAF antagonist properties in vitro. Structure-activity relationships within this series of compounds were studied extensively with respect to substituents and the position of substitution in both the aromatic and pyridinium rings. Several of these compounds (40 and 44) showed in vitro PAF antagonism at less than 0.1 microM and are as potent as CV-6209, the most potent PAF antagonist reported in the literature. Less active PAF antagonists were those bearing simple amide linkages (20-23, 27-29, and 31-35), linear imide linkages (62-63), or carbamate linkages (66 and 68), between the two aromatic rings. A number of our PAF antagonists were tested in vivo in mice and rabbits for their ability to protect these animals against a lethal injection of PAF. Those antagonists that are particularly potent (IC50 < 0.1 microM) provide excellent protection against an LD97 dose of PAF in rabbits. The relationships between structure and activity in vitro and in vivo are presented and compared to literature standards. PMID- 8496939 TI - Nonpeptide angiotensin II antagonists derived from 4H-1,2,4-triazoles and 3H imidazo[1,2-b][1,2,4]triazoles. AB - By a variety of synthetic routes, we have synthesized a series of 3,4,5 trisubstituted 4H-1,2,4-triazoles and a related series of 3H-imidazo[1,2 b][1,2,4]triazoles and evaluated them in vitro and in vivo as angiotensin II (AII) antagonists. Principal efforts focused on triazoles bearing an n-alkyl substitutent at C3 and a 4-[(2-carboxybenzoyl)amino]benzyl, (2'-carboxybiphenyl-4 yl)methyl, or [2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl side chain at N4. Among numerous variations at C5, benzylthio groups gave the best potency. Particularly noteworthy was 3-n-butyl-5-[(2-carboxybenzyl)thio]-4-[[2'-(1H-tetrazol-5-yl )biphenyl-4 - yl]methyl]-4H-1,2,4-triazole (71, IC50 1.4 nM), which blocked the AII pressor response in conscious rats at 0.3 mg/kg iv with a duration of action of approximately 6 h, similar to that of DuP 753. Although 71 was active orally only at a 10-fold higher dose level, good oral bioavailability was demonstrated for a monoacidic analogue 62. Most potent among the bicyclic derivatives was 2-n butyl-5,6-dimethyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl]- 3H imidazo[1,2-b][1,2,4]triazole (93, IC50 7.8 nM). The effects of hydrophobic, hydrogen-bonding, and ionic interactions with the AT1 receptor are considered. PMID- 8496940 TI - Synthesis and antimuscarinic activity of some 1-cycloalkyl-1-hydroxy-1-phenyl-3 (4-substituted piperazinyl)-2-propanones and related compounds. AB - A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. The objective of this study was to derive new antimuscarinic agents with potential utility in treating urinary incontinence associated with bladder muscle instability. These compounds were examined for M1, M2, and M3 muscarinic receptor selectivity in isolated tissue assays and for in vivo effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. Potency and selectivity in these assays were influenced most notably by the nature of the substituent group on the terminal nitrogen of the piperazine moiety. Benzyl substitution was particularly advantageous in producing compounds with functional M3 receptor (smooth muscle) and bladder selectivity; it provided several candidates for clinical study. In vivo, 3-(4-benzyl-piperazinyl)-1-cyclobutyl-1 hydroxy-1-phenyl-2-propanone (24) demonstrated 11- and 37-fold separations in its effect on bladder function versus mydriatic and salivation responses, respectively. The corresponding 2-chlorobenzyl derivative 25 was more than 178 fold selective for M3 versus M1 and M2 muscarinic receptors. 3-(4 Benzylpiperazinyl)-1,1-diphenyl-1-hydroxy-2-propanone (51) was 18-fold selective for M3 versus M1 and 242-fold selective for M3 versus M2 receptors. It was also selective in guinea pigs, where it displayed 20- and 41-fold separations between bladder function and effect on mydriasis and salivation, respectively. In general, the results of this study are consistent with the proposition that the described piperazinylpropanones interact with muscarcinic receptors in a hydrogen bonded form that presents a conformation similar to that apparently adopted by classical antimuscarinic agents. PMID- 8496941 TI - 5-HT3 receptor antagonists. 2. 4-Hydroxy-3-quinolinecarboxylic acid derivatives. AB - A series of 4-hydroxy-3-quinolinecarboxylic acid derivatives (6) and 4-hydroxy-2 oxo-1,2-dihydro-3-quinolinecarboxylic acid derivatives (7) were designed and synthesized as 5-HT3 receptor antagonists. Molecular modeling studies suggested that the 3-carbonyl moiety in 6 was almost coplanar to the plane of an aromatic ring, but in 7 there was a 30 degrees deviation. 4-Hydroxy substitution in quinoline derivatives enhanced affinity for the 5-HT3 receptors, and endo-N-(8 methyl-8-azabicyclo[3.2.1]oct-3-yl)-4-hydroxy-3- quinolinecarboxamide (6f) exhibited the most potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.1 micrograms/kg, iv) among quinoline derivatives 6. Although 4-hydroxy-2-oxo 1,2-dihydro-3-quinolinecarboxamide derivatives (7a) exhibited higher affinity (e.g., 7d: Ki = 0.48 nM) for the 5-HT3 receptors than ondansetron (Ki = 7.6 nM) or granisetron (Ki = 2.1 nM), these amides showed less potent activity in the B-J reflex test than the reference compounds. Interestingly, the ester derivatives 7c, 7f, and 7h eliminated affinity for the 5-HT3 receptors. These unusual structure-activity relationships and the deviation of the 3-carbonyl moiety from the plane of an aromatic ring suggest that the active conformation of 7a might be different from the proposed one for the preceding 5-HT3 antagonists. Thus, 6f was chosen for further studies. No receptor binding for a variety of ligands was significantly antagonized by 6f. Comparing the ratios of the ED50 value in the B J reflex test (rat, iv) with the LD50 value in acute lethal toxicity (mouse, iv), 6f was proved to have a 600-fold wider margin of safety than ondansetron. Compound 6f dose-dependently attenuated both the incidence and frequency of emetic episodes induced by cisplatin in the dog (ED50 = 14 micrograms/kg, iv) more potently than ondansetron (ED50 = 210 micrograms/kg, iv). Compound 6f (KF 20170) is now under further investigation as a drug for treating gastrointestinal disorder. PMID- 8496942 TI - Amidinium cation as a mimic of allylic carbocation: synthesis and squalene synthetase inhibitory activity of an amidinium analog of a carbocation intermediate. PMID- 8496943 TI - Kinetic study on the effects of intracellular K+ and Na+ on Na+, K+, Cl- cotransport of HeLa cells by Rb+ influx determination. AB - The effects of intracellular K+ and Na+ (K+c, Na+c) on the Na+, K+, Cl- cotransport pathway of HeLa cells were studied by measuring ouabain-insensitive, furosemide-sensitive Rb+ influx (JRb) at various intracellular concentrations of K+ and Na+ ([K+]c, [Na+]c). When [K+]c was increased and [Na+]c was decreased, keeping the sums of their concentrations almost constant, JRb as a function of the extracellular Rb+ or Na+ concentration ([Rb+]e, [Na+]e) was stimulated. However, the apparent K0.5 for Rb+e or Na+e remained unchanged and the ratio of the apparent K0.5 for K+c and the apparent Ki for Na+c was larger than 1. When JRb was increased by hypertonicity by addition of 200 mM mannitol, the apparent maximum JRb increased without change in the apparent K0.5 for Rb+e. These results show that K+c stimulates and Na+c inhibits JRb, without change in the affinities of the pathway for Rb+e and Na+e. The affinity for K+c is slightly lower than that for Na+c. Hypertonicity enhances JRb without any change in the affinity for Rb+e. We derived a kinetic equation for JRb with respect to K+c and Na+c and proposed a general and a special model of the pathway. The special model suggests that, in HeLa cells, JRb takes place when Rb+e binds to the external K+ binding site of the pathway after the binding of K+c to the internal regulatory site. PMID- 8496944 TI - Mechanism of activation of K+ channels by minoxidil-sulfate in Madin-Darby canine kidney cells. AB - We studied the mechanism of K+ channel activation by minoxidil-sulfate (MxSO4) in fused Madin-Darby canine kidney (MDCK) cells. Patch-clamp techniques were used to assess single channel activity, and fluorescent dye techniques to monitor cell calcium. A Ca(2+)-dependent inward-rectifying K+ channel with slope conductances of 53 +/- 3 (negative potential range) and 20 +/- 3 pS (positive potential range) was identified. Channel activity is minimal in cell-attached patches. MxSO4 initiated both transient channel activation and an increase of intracellular Ca2+ (from 94.2 +/- 9.1 to 475 +/- 12.6 nmol/liter). The observation that K+ channel activity of excised inside-out patches was detected only at Ca2+ concentrations in excess of 10 mumol/liter suggests the involvement of additional mechanisms during channel activation by MxSO4. Transient K+ channel activity was also induced in cell-attached patches by 10 mumol/liter of the protein kinase C activator 1-oleoyl-2-acetyl-glycerol (OAG). OAG (10 mumol/liter in the presence of 1.6 mmol/liter ATP) increased the Ca2+ sensitivity of the K+ channel in inside out patches significantly by lowering the Km for Ca2+ from 100 mumol/liter to 100 nmol/liter. The channel activation by OAG was reversed by the protein kinase inhibitor H8. Staurosporine, a PKC inhibitor, blocked the effect of MxSO4 on K+ channel activation. We conclude that MxSO4-induced K+ channel activity is mediated by the synergistic effects of an increase in intracellular Ca2+ and a PKC-mediated enhancement of the K+ channel's sensitivity to Ca2+. PMID- 8496945 TI - Carrier-mediated residual K+ and Na+ transport of human red blood cells. AB - Residual, i.e., (ouabain, bumetanide, and EGTA)-insensitive K+ and Na+ influxes as well as effluxes of human red blood cells are enhanced in isotonic solutions of low (NaCl + KCl) concentration using sucrose to maintain constant osmolarity. Various carrier models were tested to fit the experimental data of these fluxes simultaneously. The residual K+ and Na+ fluxes can be described on the basis of a carrier mechanism of competing substrates with modifier sites. PMID- 8496946 TI - Osmotic water permeabilities of human placental microvillous and basal membranes. AB - Literature data suggest that water accumulation by the human fetus is driven by osmotic gradients of small solutes. However, the existence of such gradients has not been supported by prior measurements. Attempts to estimate the size of the gradient necessary to drive net water movement have been seriously hampered by the lack of permeability data for the syncytiotrophoblast membranes. Stopped-flow light scattering techniques were employed to measure the osmotic water permeability (Pf) of microvillous (MVM) and basal membrane (BM) vesicles isolated from human term placenta. At 37 degrees C, the Pf was determined to be 1.9 +/- 0.06 x 10(-3) cm/sec for MVM and 3.1 +/- 0.20 x 10(-3) cm/sec for BM (mean +/- SD, n = 6). At 23 degrees C, Pf was reduced to 0.7 +/- 0.04 x 10(-3) cm/sec in MVM and 1.6 +/- 0.05 x 10(-3) cm/sec in BM. These Pf values are comparable to those observed in membranes where water has been shown to permeate via a lipid diffusive mechanism. Arrhenius plots of Pf over the range 20-40 degrees C were linear, with activation energies of 13.6 +/- 0.6 kcal/mol for MVM and 12.9 +/- 1.0 kcal/mol for BM. Water permeation was not affected by mercurial sulfhydryl agents and glucose transport inhibitors. These data clearly suggest that water movement across human syncytiotrophoblast membranes occurs by a lipid diffusion pathway. As noted in several other epithelial tissues, the basal membrane has a higher water permeability than the microvillous membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496947 TI - Ca2+ transport across intestinal brush border membranes of the cichlid teleost Oreochromis mossambicus. AB - Brush border membranes were isolated from tilapia (Oreochromis mossambicus) intestine by the use of magnesium precipitation and differential centrifugation. The membrane preparation was enriched 17-fold in alkaline phosphatase. The membranes were 99% right-side-out oriented as indicated by the unmasking of latent glyceraldehyde-3-phosphate dehydrogenase and acetylcholine esterase activity by detergent treatment. The transport of Ca2+ in brush border membrane vesicles was analyzed. A saturable and a nonsaturable component in the uptake of Ca2+ was resolved. The saturable component is characterized by a Km much lower than the Ca2+ concentrations predicted to occur in the intestinal lumen. The nonsaturable component displays a Ca2+ permeability too high to be explained by simple diffusion. We discuss the role of the saturable component as the rate limiting step in transmembrane Ca2+ movement, and suggest that the nonsaturable component reflects a transport mechanism operating well below its level of saturation. PMID- 8496948 TI - Initial steps of alpha- and beta-D-glucose binding to intact red cell membrane. AB - The kinetics of the initial phases of D-glucose binding to the glucose transport protein (GLUT1) of the human red cell can be followed by stopped-flow measurements of the time course of tryptophan (trp) fluorescence enhancement. A number of control experiments have shown that the trp fluorescence kinetics are the result of conformational changes in GLUT1. One shows that nontransportable L glucose has no kinetic response, in contrast to D-glucose kinetics. Other controls show that D-glucose binding is inhibited by cytochalasin B and by extracellular D-maltose. A typical time course for a transportable sugar, such as D-glucose, consists of a zero-time displacement, too fast for us to measure, followed by three rapid reactions whose exponential time courses have rate constants of 0.5-100 sec-1 at 20 degrees C. It is suggested that the zero-time displacement represents the initial bimolecular ligand/GLUT1 association. Exponential 1 appears to be located at, or near, the external membrane face where it is involved in discriminating among the sugars. Exponential 3 is apparently controlled by events at the cytosolic face. Trp kinetics distinguish the Kd of the epimer, D-galactose, from the Kd for D-glucose, with results in agreement with determinations by other methods. Trp kinetics distinguish between the binding of the alpha- and beta-D-glucose anomers. The exponential 1 activation energy of the beta-anomer, 13.6 +/- 1.4 kcal mol-1, is less than that of alpha-D glucose, 18.4 +/- 0.8 kcal mol-1, and the two Arrhenius lines cross at approximately 23.5 degrees C. The temperature dependence of the kinetic response following alpha-D-glucose binding illustrates the interplay among the exponentials and the increasing dominance of exponential 2 as the temperature increases from 22.3 to 36.6 degrees C. The existence of these interrelations means that previously acceptable approximations in simplified reaction schemes for sugar transport will now have to be justified on a point-to-point basis. PMID- 8496950 TI - Laparoscopic colectomy for sigmoid volvulus. AB - Laparoscopic assisted sigmoidectomy was the technique of choice for a mentally retarded adult male with severe seizure disorder and recurrent sigmoid volvulus in an effort to reduce post-op stress and discomfort and thereby diminish the possibility of exacerbation of his seizures. The technique was performed using standard laparoscopic technique and a 5cm incision in the left abdomen to perform extracorporeal bowel anastomosis. The surgery was successful and the patient experienced minimal post op discomfort, no complications and had no seizures. This newest addition to the portfolio of laparoscopic surgical techniques may be a useful tool in high risk or elderly patients who are poor candidates for conventional bowel surgery. PMID- 8496951 TI - The effects of malpractice on Mississippi physicians. AB - Medical malpractice and its effects on physicians in Mississippi is reviewed to assess its effects upon decisions in practice, patient care, and the physical and emotional toll on physicians. Through a random survey of 500 physicians in Mississippi across all areas of medicine it was determined that 47.3% of the respondents had been involved in malpractice litigation, a higher percentage than the United States average in 1989. The predominant emotional response to litigation was anger. Most physicians did not seek outside help as an aid in coping. PMID- 8496949 TI - Allosterism and Na(+)-D-glucose cotransport kinetics in rabbit jejunal vesicles: compatibility with mixed positive and negative cooperativities in a homo- dimeric or tetrameric structure and experimental evidence for only one transport protein involved. AB - We first present two simple dimeric models of cotransport that may account for all of the kinetics of Na(+)-D-glucose cotransport published so far in the small intestine. Both the sigmoidicity in the Na+ activation of transport (positive cooperativity) and the upward deviations from linearity in the Eadie-Hofstee plots relative to glucose concentrations (negative cooperativity) can be rationalized within the concept of allosteric kinetic mechanisms corresponding to either of two models involving sequential or mixed concerted and sequential conformational changes. Such models also allow for 2 Na+: 1 S and 1 Na+: 1 S stoichiometries of cotransport at low and high substrate concentrations, respectively, and for partial inhibition by inhibitors or substrate analogues. Moreover, it is shown that the dimeric models may present physiological advantages over the seemingly admitted hypothesis of two different cotransporters in that tissue. We next address the reevaluation of Na(+)-D-glucose cotransport kinetics in rabbit intestinal brush border membrane vesicles using stable membrane preparations, a dynamic approach with the Fast Sampling Rapid Filtration Apparatus (FSRFA), and both nonlinear regression and statistical analyses. Under different conditions of temperatures, Na+ concentrations, and membrane potentials clamped using two different techniques, we demonstrate that our data can be fully accounted for by the presence of only one carrier in rabbit jejunal brush border membranes since transport kinetics relative to glucose concentrations satisfy simple Michaelis-Menten kinetics. Although supporting a monomeric structure of the cotransporter, such a conclusion would conflict with previous kinetic data and more recent studies implying a polymeric structure of the carrier protein. We thus consider a number of alternatives trying to reconcile the observation of Michaelis-Menten kinetics with allosteric mechanisms of cotransport associated with both positive and negative cooperativities for Na+ and glucose binding, respectively. Such models, implying energy storage and release steps through conformational changes associated with ligand binding to an allosteric protein, provide a rational hypothesis to understand the long-time debated question of energy transduction from the Na+ electrochemical gradient to the transporter. PMID- 8496952 TI - Back then--plus ten commandments for graduates with illustrative cases. PMID- 8496953 TI - Home health reimbursement. PMID- 8496954 TI - New recommendations for annual adolescent check-ups. PMID- 8496955 TI - Genetic evidence for the interaction between cluster I and cluster III rifampicin resistant mutations. AB - Rifampicin-resistant (Rifr) mutations of Escherichia coli map to the central portion of the rpoB gene, which encodes the beta subunit of RNA polymerase. These mutations are located in three distinct clusters, designated I, II and III. Three intragenic suppressors of the cluster III Rifr mutation, rpoB3406(RH687), restore the ability of the mutant strain to grow at low and high temperatures and map to a single locus in cluster I. These suppressors are identical to two previously characterized Rifr alleles, rpoB3401(RC529) and rpoB3402(RS529). None of the other 14 previously identified Rifr mutations that we have characterized confers this phenotype. We suggest that this allele-specific suppression results from interaction between Cluster I and Cluster III of the beta subunit. PMID- 8496956 TI - Three-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complex. AB - The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3 also cross-reacts with similar affinity with a subgroup of structurally distinct, progesterone-like steroids. Crystals of the unliganded Fab' and various steroid Fab' complexes are isomorphous and belong to the hexagonal space group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A. Structures of free and progesterone-bound Fab' have been determined by X-ray crystallography at 2.7 A resolution using molecular replacement techniques. Progesterone is bound in a hydrophobic pocket formed mainly by the interaction of three complementarity determining regions L1, H2 and H3. The orientation of the ligand in the binding site was aided by both crystallographic and biochemical analyses of substituted steroids. The indole side-chain of TrpH100 of the DB3 has two different conformations, inter-converting "open" and "closed" forms of the antibody combining site. The TrpH100 indole thus appears to be acting as an antibody derived surrogate ligand for its own hydrophobic binding pocket. These structures provide the first atomic view of how a steroid interacts with a protein and offer a structural explanation for the restriction of the anti-progesterone response to the VGAM3.8 family of VH genes. PMID- 8496957 TI - Human erythrocyte band 3. Solubilization and reconstitution into two-dimensional crystals. AB - Various polyoxyethylene alkylethers were used to extract integral proteins from human erythrocyte membranes. The solubilization power of these detergents and the oligomerization of solubilized band 3 were studied. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that short-chain detergents induced oligomers larger than the band 3 dimer. In contrast, after solubilization with long-chain detergents, the predominant band on SDS-containing gels was the monomeric band 3. Oligomerization in short-chain detergents occurred preferentially at room temperature whereas monomeric band 3 prevailed at 4 degrees C. Consistent with these results, negative stain electron microscopy of solubilized isolated band 3 showed larger complexes with short-chain detergents than with long-chain detergents. Cu2+/o-phenanthroline-induced crosslinking had no effect on size or shape of band 3 particles. Despite their rather heterogeneous dimensions, octylpolyoxyethylene-solubilized band 3 complexes assembled into two-dimensional trigonal lattices (a = b = 11 (+/- 0.5) nm) in the presence of dimyristoyl phosphatidylcholine. The unit cell exhibited a pronounced stain-filled region surrounded by three elongated morphological subunits. Each subunit most likely represents a band 3 dimer. Freeze-drying/metal-shadowing of reconstituted lattices revealed one large elevation per unit cell protruding from an otherwise smooth surface. PMID- 8496958 TI - Preliminary crystallographic analysis of a Fab specific for the O-antigen of Shigella flexneri cell surface lipopolysaccharide with and without bound saccharides. AB - The Fab of a monoclonal anti-carbohydrate antibody, SYA/J6 (IgG3, kappa, murine), raised against the O-polysaccharide antigen of the cell surface lipopolysaccharide of variant Y Shigella flexneri, a Gram negative bacterium, has been crystallized in the unliganded form and in complex with tri- and pentasaccharide antigens. The three crystal forms belong to the tetragonal space group P4(3)2(1)2, or P4(1)2(1)2, with very similar unit cell dimensions and an asymmetric unit that contains one molecule of about 50,000 Daltons, and a fourth crystal form belongs to monoclinic space group P2(1) that contains four molecules of Fab in an asymmetric unit. Whereas diffractions of these crystals on an area detector-rotating anode system extend to only about 3.5 A resolution, those measured using an imaging plate and synchrotron radiation at the Photon Factory facility extend to 2.5 A. PMID- 8496959 TI - Crystallization and preliminary X-ray analysis of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. AB - Ribonuclease inhibitor was purified from pig liver and crystallized at 21 degrees C from solutions containing dithiothreitol as an additive and ammonium sulfate, lithium sulfate or combinations of both as precipitants. Crystals have the symmetry of the tetragonal space group I4 with a = 134.9 A and c = 83.6 A, and diffract to better than 3 A resolution. Self rotation functions and packing density of the crystals are consistent with two molecules in the asymmetric unit. PMID- 8496960 TI - Purification and crystallization of fumarase C from Escherichia coli. AB - Fumarase C purified from Escherichia coli has been crystallized in the presence of polyethylene glycol in both a citrate buffer at pH 5.3 and a 3-(4-morpholino) propanesulfonic acid buffer at pH 7.5 yielding two crystal forms. An orthorhombic C222(1) form was obtained in citrate at pH 5.3 and an orthorhombic I222 form was obtained in 3-(4-morpholino)-propanesulfonic acid (pH 7.5). Complete native data sets have been collected on both crystal forms: the C222(1) form is complete to 2.10 A and the I222 form is complete to 2.20 A. PMID- 8496961 TI - Crystallization and preliminary X-ray analysis of the periplasmic dipeptide binding protein from Escherichia coli. AB - The periplasmic dipeptide-binding protein from Escherichia coli has been purified, freed of bound endogenous ligands, and crystallized. Crystals of the protein in complex with added dipeptides have been subjected to X-ray analysis. The crystals grow as hexagonal bipyramids or eye-shaped disks which have the symmetry of space group P6(1). The unit cell dimensions are a = b = 183 A, c = 212 A, and the diffraction pattern extends to 3.2 A resolution with a conventional X-ray source. PMID- 8496962 TI - Sequences of sea urchin kinesin light chain isoforms. AB - We have deduced the amino acid sequences of four sea urchin (Strongylocentrotus purpuratus; SP) kinesin light chain (KLC) isoforms (SPKLC 1-4) and compared them to rat brain light chain sequences. Examination of the SPKLC open reading frames (SPKLC1, 649; SPKLC2, 677; SPKLC3, 686; and SPKLC4, 451 amino acid residues) reveals that the first 500 or so residues of the KLCs are highly conserved but the C-terminal ends of rat and sea urchin light chains are divergent; SPKLCs 1, 2 and 3 share a highly basic, 86 residue C-terminal segment that is missing from the shorter rat light chains and SPKLC4. The insertion of 28 and 37 residue segments at residue 563 of SPKLCs 2 and 3, respectively, gives rise to sequence heterogeneity at the C-terminal ends of the sea urchin KLCs. C-terminal sequence differences between light chains may provide inter- and intraspecies differences in the functional properties of the presumptive cargo attachment elements of kinesin. PMID- 8496963 TI - Conformation of the origin of P1 plasmid replication. Initiator protein induced wrapping and intrinsic unstacking. AB - The origin of plasmid DNA replication in bacteriophage P1 has five 19 base-pair sites that bind the plasmid-encoded initiator, RepA. Here we show, using a DNA band retardation assay, that RepA can bend DNA that carries one or more of the RepA binding sites. RepA binding to supercoiled DNA carrying the five sites, directly repeated and phased two turns of B-DNA apart, absorbs about one positive superhelical turn of DNA as determined by two-dimensional gel electrophoresis. This indicates that the DNA is wrapped around RepA as a consequence of in-phase bending at the individual binding sites. The RepA-DNA complexes did not show elevated sensitivity to KMnO4, a reagent specific for pyrimidine bases (T >> C) in unstacked DNA. The wrapping of the DNA around RepA, therefore, does not lead to significant unwinding of the double helix. Extensive unwinding, suitable for the initiation of DNA replication, most likely requires participation of factors other than RepA. We also noted that the thymine bases of the sequence 5'-ATC-3', of which there are 20 in the origin, all reacted to KMnO4 strongly whether or not RepA was present. The preferential reactivity of ATC sequences was specific to the origin region, as thymine residues including those in the ATC sequences did not display elevated sensitivity to KMnO4 in a DNA fragment from pBR322. On one of two strands of the origin the selective reactivity at the ATC sequences was supercoiling dependent. These results indicate that the origin includes unstacked DNA bases, the significance of which remains to be determined. PMID- 8496964 TI - The LexA repressor binds within the deep helical groove of the activated RecA filament. AB - The RecA protein of Escherichia coli, as a result of DNA damage, catalyzes the cleavage of its own repressor, the LexA protein, and thereby initiates the SOS response. Using a non-cleavable LexA mutant, we have obtained a co-complex of both the RecA and LexA proteins on DNA. Mass analysis using scanning transmission electron microscopy suggests that the site size of the LexA repressor on RecA is two, which would be consistent with a nearest-neighbor exclusion model for binding. Three-dimensional reconstruction of electron micrographs of these filaments shows that the LexA protein is bound in the deep groove of the RecA filament, with two strong regions of contact that span adjacent RecA protomers within the filament. One contact is consistent with a proposed LexA binding site in the RecA crystal structure. The other contact maps onto a region that has been postulated to be a second DNA-binding site within RecA, which can explain the inhibition of RecA cleavage of LexA by excess DNA. PMID- 8496965 TI - Analysis of mutations occurring at the human hprt locus. AB - We have recently established a computerized database containing information on mutants at the human hypoxanthine guanine phosphoribosyl transferase (hprt) locus. The database contains sequence information on over 1000 mutants. We now present an analysis of the information in the database. 542 single base substitution mutants in the hprt coding region exist, and we have examined (1) the number of mutations and the number of mutable sites in each exon, (2) transcribed versus non-transcribed strand bias for mutations, (3) the frequency of the 5' and 3' nearest neighbors to a mutated base, and (4) the distribution of amino acid substitutions. The distribution of both DNA mutations and amino acid mutations was not uniform, several clusterings of mutations were observed and we propose several possible mechanisms to account for the hotspots. We also examined mRNA splicing mutants, mutants with small deletions, and frameshift mutants. PMID- 8496966 TI - Three-dimensional transformation of capsids associated with genome packaging in a bacterial virus. AB - Three-dimensional structures of the empty procapsid and the mature capsid of the Salmonella bacteriophage P22 have been determined to a resolution of 28 A using electron cryomicroscopy and computer image processing. The coat subunits in both the structures are arranged as pentamers and hexamers on a T = 7 icosahedral lattice. The two structures display significant differences in shape, size and intersubunit interactions. The empty procapsid is spherical in contrast to the distinctly larger and polyhedral mature capsid. The empty procapsid structure exhibits holes at all the quasi sixfold positions that are absent in the mature capsid. These holes may be the exit ports for scaffolding subunits. Detailed comparisons of the two structures indicate that extensive structural changes take place during maturation in all seven quasi-equivalent subunits. These changes cause flattening of the icosahedral facets, capsid expansion and closing of the holes. This process results in a stable and impenetrable capsid that protects the bacterial genome. PMID- 8496967 TI - Genetic algorithms for protein folding simulations. AB - Genetic algorithms methods utilize the same optimization procedures as natural genetic evolution, in which a population is gradually improved by selection. We have developed a genetic algorithm search procedure suitable for use in protein folding simulations. A population of conformations of the polypeptide chain is maintained, and conformations are changed by mutation, in the form of conventional Monte Carlo steps, and crossovers in which parts of the polypeptide chain are interchanged between conformations. For folding on a simple two dimensional lattice it is found that the genetic algorithm is dramatically superior to conventional Monte Carlo methods. PMID- 8496968 TI - Exploring the limits of precision and accuracy of protein structures determined by nuclear magnetic resonance spectroscopy. AB - The effects of the number, precision and accuracy of interproton distance restraints, of direct refinement against nuclear Overhauser enhancement (NOE) intensities and of the description of the non-bonded contacts on the precision and accuracy of a nuclear magnetic resonance (NMR) protein structure determination have been investigated. The model system employed is the 56 residue immunoglobulin G binding domain of streptococcal protein G. This choice was based on the availability of a very high resolution NMR structure (atomic root-mean square distribution of the ensemble of 60 calculated structures about the mean co ordinate positions of 0.25 A for the backbone atoms, 0.65 A for all atoms and 0.39 A for all atoms excluding disordered surface side-chains). The experimental NMR data set for this structure determination comprised a total of 1058 experimental restraints of which 854 were approximate interproton distance restraints corresponding to all the structurally useful NOEs observable for this protein. The calculations presented in this paper reveal the following. (1) The number of interproton distance restraints constitutes the single most important determinant of both precision and accuracy. The ensemble precision and accuracy improves significantly as the number of interproton distance restraints is increased to an average of approximately 15 per residue, of which approximately 60% involve unique proton pairs; subsequent additions of interproton distance restraints, however, lead to less dramatic improvements as information redundancy sets in. (2) The ratio of ensemble precision to ensemble accuracy (which ranges from 0.5 to 0.7 for the backbone atoms) is approximately independent both of the number, precision and accuracy of the interproton distance restraints, and of whether the structures are refined against interproton distance restraints or directly against NOE intensities. (3) In an ensemble of structures generated from a large number of loose approximate interproton distance restraints (an average of approximately 15 restraints per residue with approximately 60% involving unique proton pairs), the interproton distance vectors corresponding to the restraints are very well defined with approximately 80% of vectors between unique proton pairs having a standard deviation of < or = 0.1 A. (4) The accuracy of the mean co-ordinates of an ensemble of structures is significantly higher than the average accuracy of the individual structures comprising the ensemble. For an average ensemble precision of > or = 0.6 A, the dependence of the accuracy of the mean co-ordinates on ensemble precision is approximately linear.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8496969 TI - In-series fiber architecture in long human muscles. AB - The fiber architecture of adult human sartorius and gracilis muscles was examined using a combination of fiber microdissections and histological methods. Intact fibers were dissected from fascicles of muscle strips that were digested in nitric acid. All of these fibers terminate intrafascicularly by tapering to a fine strand at one or both ends. They measure 4-20 cm after correction for shrinkage. Systematic dissections of 1 cm long blocks sampled at intervals along the muscle length suggest that tapered fiber endings occur at all locations along the muscle but are most common centrally; here they accounted for up to 14% of dissected fibers in each block. Transverse sections of muscle confirm that fiber profiles with small diameters occur at all levels of the muscle but are especially common in sections more than 5 cm from its origin or insertion. The architectural arrangement demonstrated here suggests that long human muscles, like muscles in other species, are composed of relatively short, in-series fibers. This has many implications for the neural activation and force-developing behavior of these muscles that must be considered when paralyzed muscles are reanimated using electrical stimulation. Further, it may predispose long muscles to certain types of neuromuscular damage and dysfunction. PMID- 8496970 TI - Suboccipital muscles in the cat neck: morphometry and histochemistry of the rectus capitis muscle complex. AB - The morphometry, histochemistry, and biomechanical relationships of rectus capitis muscles were examined in adult cats. This family of muscles contained six members on the dorsal, ventral, and lateral aspects of the upper cervical vertebral column. Three dorsal muscles (rectus capitis posterior major, medius, and minor) formed a layered complex spanning from C1 and C2 to the skull. Rectus capitis posterior major was composed predominantly of fast fibers, but the other two deeper muscles contained progressively higher proportions of slow fibers. One ventral muscle, rectus capitis anterior major, was architecturally complex. It originated from several cervical vertebrae and appeared to be divided into two different heads. In contrast, rectus capitis anterior minor and rectus capitis lateralis were short, parallel-fibered muscles spanning between the skull and C1. The ventral muscles all had nonuniform distributions of muscle-fiber types in which fast fibers predominated. Dorsal and ventral muscle groupings usually had cross-sectional areas of 0.5 cm2 or more, reflecting a potential capacity to generate maximal tetanic force in excess of 9 N. Biomechanical analyses suggested that one muscle, rectus capitis lateralis, had its largest moment in lateral flexion, whereas the other muscles had large, posturally dependent moment arms appropriate for actions in flexion-extension. The observation that most rectus muscles have relatively large cross-sectional areas and high fast-fiber proportions suggests that the muscles may have important phasic as well as postural roles during head movement. PMID- 8496971 TI - Observations on the development of unusual melanization of leopard frog ventral skin. AB - The ontogeny of ventral pigmentation of two species of leopard frog, Rana pipiens and R. chiricahuensis, was examined by light microscopy and transmission electron microscopy to reveal how the unusual melanistic ventral pigmentation of R. chiricahuensis is achieved at the cellular level. Ventral skin of R. pipiens is always white. Ventral skin of adult R. chiricahuensis is white when frogs are background-adapted to a white substrate, but ventral skin becomes nearly as dark colored as the dorsal skin when frogs darken in response to a black background. Skin samples from tadpoles of both species, newly metamorphosed frogs, and adult frogs were analyzed for chromatophore composition and distribution. Ventral skin of R. pipiens larvae, newly metamorphosed frogs, and adults and of R. chiricahuensis larvae was white due to abundant iridophores and no melanophores. Melanophore density in the ventral integument of R. chiricahuensis was 9.1 +/- 2.8/mm2 in newly metamorphosed frogs and 87.0 +/- 4.8/mm2 in adult frogs. Pigment within ventral melanophores migrated during physiological color change during background adaptation. PMID- 8496972 TI - Ultrastructure of prothoracic glands during larval-pupal development of the tobacco hornworm, Manduca sexta: a reappraisal. AB - The structure of Manduca sexta prothoracic glands was investigated using a protocol that preserves membranes. During the last larval stadium, prothoracic gland cells increase in diameter, volume, protein content, and perhaps number, enhancing their capacity to produce ecdysteroids. The glands' strand-of-cells morphology, their in situ location, the presence of gap junctions between cells, and junctional foot-like structures within cells support previous findings that prothoracicotropic hormone stimulates ecdysteroidogenesis via Ca(2+)-induced Ca2+ release. A different method of tissue fixation from that previously used to investigate the ultrastructure of Manduca sexta prothoracic glands has revealed a significantly different ultrastructure. These new findings begin to define roles for endoplasmic reticulum and mitochondria in ecdysteroid synthesis and support the hypothesis that the glands secrete the steroid hormone via exocytosis. The structural dynamics of the glands are discussed in the context of the glands' function during Manduca sexta larval-pupal development. PMID- 8496973 TI - Cytokine release in an ovarian carcinoma patient following intravenous administration of bispecific antibody OC/TR F(ab')2. PMID- 8496974 TI - Hypothesis: coffee consumption, N-acetyltransferase phenotype, and cancer. PMID- 8496975 TI - Marked fluctuations in drug plasma concentrations caused by use of portable pumps for fluorouracil continuous infusion. PMID- 8496976 TI - Limited role of vasculature-mediated injury in tumor response to radiotherapy. PMID- 8496977 TI - ASCO/AACR: shared emphases and separate meetings. PMID- 8496978 TI - Radiation after quadrantectomy questioned for older women. PMID- 8496979 TI - Stem-cell treatment brings a historic week in gene therapy. PMID- 8496980 TI - Committee recommends triple attack on breast cancer. PMID- 8496981 TI - Intersociety Council on Radiation Oncology essay on the introduction of new medical treatments into practice. PMID- 8496982 TI - p53 as an independent prognostic marker in lymph node-negative breast cancer patients. AB - BACKGROUND: At present, most decisions concerning the use of adjuvant therapy in lymph node-negative breast cancer patients are made on the basis of traditional factors such as tumor size, nodal status, and histopathologic features. However, prognostic factors are being investigated that could identify high-risk groups and that could better address treatment efforts for those patients. Identification of more accurate prognostic markers, such as the expression of the mutant p53 protein encoded by the p53 (also known as TP53) tumor suppressor gene, that are reproducible, easily assessable, and independent in predicting clinical outcome would have a beneficial impact on cancer treatment decisions. PURPOSE: Our purpose was to analyze the predictive relevance of mutant p53 protein expression on 6-year relapse-free and overall survival in node-negative breast cancer patients in relation to menopausal status, tumor size, cell kinetics, and estrogen receptor status. METHODS: Expression of mutant p53 protein was detected by an immunohistochemical technique using a 1:50 dilution of PAb1801 monoclonal antibody on paraffin-embedded tumor specimens obtained from 256 axillary lymph node-negative breast cancer patients, with long-term follow-up (median, 72 months). The [3H]thymidine labeling index, a measure of cell kinetics, was evaluated on histologic sections after fresh tumor tissue was labeled with [3H]thymidine. Estrogen receptor status was determined by the dextran-coated charcoal absorption technique. Statistical comparisons were made for levels of p53 protein expression, [3H]thymidine labeling index, estrogen receptor status, tumor size, and menopausal status with respect to 6-year relapse-free survival and overall survival. RESULTS: Overexpression of the p53 protein, defined as the presence of more than 5% positive cells, was detected in 113 (44%) of 256 tumors. Odds ratios (ORs) for multiple regression analysis of 6-year relapse-free survival were significantly higher for p53 (OR = 3.24; 95% confidence limits [CL] = 2.01-5.23) and [3H]thymidine labeling index (OR = 1.92; 95% CL = 1.19-3.12), both of which appeared to be the most relevant indicators of relapse, than for tumor size (OR = 1.49; 95% CL = 0.94-2.38) and estrogen receptor status (OR = 0.91; 95% CL = 0.55-1.51). Overexpression was found to be unrelated to menopausal status. CONCLUSIONS: Immunohistochemically detected p53 overexpression is an independent marker for shortened 6-year relapse-free and overall survival in node negative patients with resectable breast cancers. Based on these findings, p53 overexpression should be used with other established prognostic factors, such as [3H]thymidine labeling index and estrogen receptor status, to further refine the prognostic assessment of node-negative breast cancer. PMID- 8496983 TI - Noncancer deaths in white adult cancer patients. AB - BACKGROUND: The cancer-specific death rate is a commonly used indicator in the assessment of progress against cancer. However, since the cause of death is often not substantiated and complete medical information is lacking, the validity of cancer-specific mortality rates is being questioned. PURPOSE: We investigated the validity of the cancer-specific death rate by examining noncancer deaths of cancer patients in a large patient population. METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program on cancer patients diagnosed between 1973 and 1987, with follow-up complete through December 1987. The SEER database consists of 1.2 million records from nine population-based registries covering nine geographic regions of the United States. Rates of noncancer deaths in the U.S. population were obtained from the National Center for Health Statistics. Cancer mortality rates were subtracted from overall mortality rates to obtain noncancer death rates by sex and the 5-year age group for each calendar year. Excluded from the study were patients of races other than White and those diagnosed at age 85 years or more due to absence of noncancer death rate comparisons. Also excluded were cancer cases discovered at autopsy and in persons less than 20 years of age. The statistical analysis employed a log-linear model. RESULTS: The ratio of patient to-general-population noncancer death rates, as calculated by dividing the number of patient noncancer deaths per year by the number found in the matched U.S. population data and referred to as the noncancer relative hazard, is considered significant with values greater than 1 for those with all cancers combined and for the common solid tumors examined. Of the 12 leading causes of death other than cancer in the patient population, the most common causes were circulatory and respiratory failures. The noncancer relative risk of death decreased rapidly after diagnosis and also decreased with the patient's age at diagnosis. It increased slightly with the calendar year of diagnosis. CONCLUSIONS: Because more noncancer deaths occurred shortly after diagnosis, it appears that this excess was caused by treatment of the cancer. Generally, cancer-specific death rates underestimate the mortality associated with a diagnosis of cancer. Therefore, because the degree of underestimation changes with time, an examination solely of cancer-caused mortality in assessing progress against the disease is incomplete. PMID- 8496985 TI - National Medical Association's health-care reform recommendations to the President's Task Force on Health. PMID- 8496984 TI - Impact of stromal sensitivity on radiation response of tumors. AB - BACKGROUND: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e.g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. PURPOSE: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. METHODS: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. RESULTS: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). CONCLUSIONS: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression. PMID- 8496986 TI - Anatomical variation, human diversity, and environmental adaptation. PMID- 8496987 TI - The acceptability of the female condom among low-income African-American women. AB - Among women, African Americans are at the highest risk for contracting the human immunodeficiency virus (HIV). Unfortunately, the majority of African-American women do not perceive themselves to be at risk nor perceive the need to engage in safe-sex practices. Given the alarming rate of increase of HIV disease among African-American women, more in-depth information about the sociocultural factors influencing these nonhealth-promoting beliefs and behaviors is needed immediately in order to design effective Information, Education, Communication campaigns. As part of such an effort, a premarketing study of the recently developed female condom, Reality (Wisconsin Pharmacal, Jackson, Wisconsin), was used as an opportunity to assess not only acceptance and relevance of the product, but also knowledge, attitudes, and practices among a group of African-American women in New Orleans. The methodology chosen was focus group discussions. The main finding from these discussions is that the previously reported low-risk perception of HIV disease among African-American females is also true among this group. The discussions suggest that cultural norm of female submission and passivity in sexual negotiation is a major barrier to preventive actions among these African American women, ie, insistence on condom use during sexual intercourse [corrected]. The second important finding from these focus group discussions is that the women enthusiastically endorsed the female condom because they felt this condom allowed them control over safe-sex practices without having to challenge the power of their male partners. This study also demonstrates that the dynamics of universality and interpersonal learning inherent to insight-oriented or support groups can also be present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8496988 TI - Impact of intrauterine exposure to phencyclidine (PCP) and cocaine on neonates. AB - A total of 505 newborns who were exposed to illicit drugs during intrauterine life were studied to investigate the prevalence, growth parameters, newborn manifestations, and other effects of intrauterine exposure to cocaine and phencyclidine (PCP). The results support the hypotheses that both drugs have serious effects on growth parameters, but this effect was much more pronounced in the cocaine group than in the PCP group. Furthermore, the incidence of borderline microcephalic infants (head circumferences less than the 10th percentile) was much higher in the cocaine group. It also appears that the signs and symptoms observed in both groups are not withdrawal manifestations typically seen in narcotic-exposed infants; rather, these symptoms are true drug effects and should not be considered manifestations of drug withdrawal symptoms. PMID- 8496989 TI - Organ donation in the African-American population: a fresh perspective with a simple solution. AB - Organ transplantation is seriously limited by a lack of available organs. This article focuses on the more pronounced lack of organ donation within the African American population and discusses the consequences of this trend. The reasons for this population's continued reluctance to donate organs are reviewed in detail and current efforts to improve donation rates are outlined. The solution proposed in this article is to acknowledge and use resources already active in the community in efforts to increase organ donation rates within the African-American population. Social workers, teachers, religious leaders, and transplant donors, recipients, and their families would all provide a crucial addition to the multidisciplinary team already involved with organ donation efforts. PMID- 8496990 TI - Magnetic resonance imaging of the central nervous system in children with a new nonionic gadolinium contrast agent--gadoteridol injection (ProHance). AB - This article reports the results of clinical testing in pediatric patients of a new contrast agent, gadoteridol injection (ProHance), developed by Squibb Diagnostic as a nonionic gadolinium agent for use in magnetic resonance imaging (MRI). Thirteen children (four girls and nine boys) ranging in age from 10 to 18 years were enrolled in the study. The children had MR studies of the brain and/or spine with T1-weighted, T2-weighted, and postgadoteridol injection T1-weighted sequences. Five children had primary brain or spine neoplasms, three children had metastatic disease to the central nervous system, one child had a recurrent brain neoplasm and spinal canal metastasis, one child had an arteriovenous malformation, and two children were normal on the MRI studies. No minor or major reactions to gadoteridol injection developed in the 13 patients. Gadoteridol injection provided excellent delineation and enhancement of the arteriovenous malformation and all of the primary and secondary neoplasms of the central nervous system except for one case of a grade 1 glioma of the midbrain. Gadoteridol injection is a safe and excellent contrast agent for use in MRI. PMID- 8496991 TI - Racial differences in clinical and social variables among patients evaluated in a dementia assessment center. AB - Despite increased interest in dementia and the concomitant creation of dementia assessment centers, there has been a paucity of reports examining racial differences in the social and clinical presentation of dementia. Such information can enhance knowledge about dementia and assist in the planning of diagnostic centers located in areas with large minority populations. This study reviewed the charts of patients evaluated at a dementia assessment center in New York City. The sample comprised 102 white and 68 black patients. There were no racial differences in types of dementia nor reported length of illness. However, bivariate analysis revealed many significant differences between the groups in social, medical, and psychiatric variables. Most notably, a stepwise discriminant analysis identified seven variables--Medicaid recipient, gender, age, sleep disturbances, delusions of stealing, hypertension, and concentration--as correctly being able to classify 75% of cases. Racial differences in cognitive and behavioral symptoms may reflect the interaction of dementia with physical health, premorbid history, environment, or some basic difference in disease course. PMID- 8496992 TI - The sickle gene: a marker for blood pressure? AB - Blood pressure patterns were studied in 224 Nigerians comprising 22 families with at least one child with sickle cell anemia (SS) and 18 families without sickle cell anemia (AA) in a community with a high frequency of the sickle trait (AS). Among the offspring (n = 162; mean age: 10.1 years), systolic blood pressure did not differ between the SS, AS, or AA groups. However, the SS group had significantly lower diastolic blood pressure than the AS or AA groups (60.6 versus 66.5 and 65.4 mm Hg, respectively; P < .01). After controlling for genotype, age, body mass index, and sex, regression analysis revealed that age was the only independent correlate of blood pressure. PMID- 8496993 TI - Incidence of bacterial respiratory pathogens and their susceptibility to common antibacterial agents. AB - Although most respiratory tract infections are caused by viruses, bacterial pathogens are responsible for higher morbidity and mortality. Because virtually nothing is known about the etiology of bacterial respiratory pathogens in Saudi Arabia, this study examined the incidence of these organisms in 5426 patients over a 1-year period. Of the bacterial pathogens isolated from 904 patients, the most common organism was Hemophilus influenzae (31%), followed by pneumococci (22%), Pseudomonas aeruginosa (16%), and others (31%). Because the first two organisms accounted for more than 50% of isolates, their susceptibility to commonly used antibiotics was also reviewed. The results are presented here. PMID- 8496994 TI - Polymicrobial polyfocal osteomyelitis and polymicrobial urinary tract infection in sickle cell disease--a case report. AB - Salmonella osteomyelitis is a well-known association of patients with sickle cell disease. This case report describes an infant with osteomyelitis having multiple foci and two pathogens including Salmonella and Staphylococcus aureus who was treated successfully. An additional unusual feature included urinary tract infection. PMID- 8496995 TI - The Morehouse School of Medicine story: a surgical strike! The 1992 Sinkler Memorial Lecture. PMID- 8496996 TI - Blunt abdominal trauma in children: the practical value of ultrasonography. AB - The occult nature of blunt abdominal trauma justifies the need for reliable diagnostic adjuncts to physical examination. From June 1988 to June 1991, 259 children admitted to the general surgery/trauma service underwent abdominal ultrasonographic scanning (US). A total of 116 abdominal lesions were found in 81 patients. Ultrasonography alone had a sensitivity of 89%, a specificity of 96%, and an overall accuracy of 94%, as determined against the overall diagnostic workup and clinical course (mean follow-up, 17.4 weeks). In 44% of the patients, US was used alone; in 49% one or two additional tests were performed, and in only 7% were three or more tests required. Compared with computed tomography, US is more versatile, easier to perform in children, and more cost effective, even with the addition of a functional imaging modality. Although not demonstrated by this preliminary, retrospective study, Doppler US appears to be the logical complement to abdominal ultrasonography in the evaluation of children with blunt abdominal trauma. PMID- 8496997 TI - Early enteral feeding does not attenuate metabolic response after blunt trauma. AB - Enteral feeding very early after trauma has been hypothesized to attenuate the stress response and to improve patient outcome. We tested this hypothesis in a prospective, randomized clinical trial in patients with blunt trauma. Following resuscitation and control of bleeding, 52 patients were randomized to receive early feedings (target, < 24 hours) or late feedings (target, 72 hours). Feeding was given via nasoduodenal feeding tubes. A rapid advance technique was used to achieve full volume and strength within 24 hours (goal, 1.5 g protein/kg.day). Patients who underwent at least 5 days of therapy were considered to have completed the study: 38 in all, 19 in each feeding group. Patients were similar in age, gender, Injury Severity Score, and mean PaO2/FiO2 ratio. The early group, however, had more patients with a PaO2/FiO2 < 150. After feeding began, the amount fed per day was the same in both groups. We found no significant differences in metabolic responses as measured by plasma lactate and urinary total nitrogen, catecholamines, and cortisol. Both groups achieved nitrogen retention. In addition, we found no significant differences in intensive care unit (ICU) days, ventilator days, organ system failure, specific types of infections, or mortality, although the early group had a greater number of total infections. In this study, early enteral feeding after blunt trauma neither attenuated the stress response nor altered patient outcome. PMID- 8496998 TI - Restoration of gut absorptive capacity following trauma-hemorrhagic shock by the adjuvant use of heparan sulfate. AB - The aim of this study was to investigate whether heparan sulfate, as an adjunct to resuscitation following hemorrhagic shock: (1) improves gut absorptive capacity and if so, (2) whether the mechanism involved is alteration of whole blood viscosity (WBV). Rats were anesthetized, a laparotomy performed, and blood vessels cannulated. The conscious animals then underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with lactated Ringer's solution. One group received 7 mg/kg heparan sulfate, and another received saline, during resuscitation. At 2 hours and 4 hours after the end of hemorrhage, the oral D xylose absorption test was performed. Viscosity determinations were made in another set of rats since lactated Ringer's solution replacement during the D xylose test may affect hematocrit and hence WBV. These rats were subjected to hemorrhage and resuscitation as above, along with additional sham hemorrhage and acute hemodilution control groups. The WBV was determined at corresponding times to the D-xylose test. Results show that xylose absorption is depressed after hemorrhage and resuscitation, and heparan sulfate restored it to normal. The WBV was reduced by heparan sulfate. Thus heparan sulfate, as an adjunct to resuscitation of hemorrhagic shock, restores gut absorptive capacity to normal, possibly by reducing WBV. PMID- 8496999 TI - Is the metabolic response to injury different with or without severe head injury? Significance of plasma glutamine levels. AB - Acute brain injury is the single largest cause of trauma center deaths. Injury that does not involve the brain directly can lead to a cascade of changes in neuroendocrine system function. In order to evaluate the effect of head injury in severely traumatized patients on the response of body fuel mobilization and utilization, 42 adult patients were studied in the early "flow" phase of injury in the fasting state. They were divided into two groups: (1) multiple trauma patients without head injury (MI group, n = 21); and (2) multiple trauma patients with severe head injury (HMI group, n = 21). This enabled evaluation of the influence of injured brain on the general response to body injury. Kinetic measurements of protein (primed-constant infusion of 15N glycine), glucose (14C and 3H isotopic glucoses), fat (two-stage glycerol infusion), and energy metabolism (indirect calorimetry) were made along with hormone and substrate determinations. The results of this integrated approach demonstrated similar hormonal and metabolic changes between these two groups of patients. However, hepatic glucose production and whole body lipolysis rates were significantly decreased in HMI patients. In addition, hyperglycemia and hypoglutaminemia were more pronounced in injured patients with associated head injury. Glutamine release, which forms a significant net release of brain amino acids in normal subjects may be impaired in HMI patients. Associated brain injury appears to moderate the systemic effect of trauma. PMID- 8497000 TI - Wound closure and outcome in extensively burned patients treated with cultured autologous keratinocytes. AB - Cultured autologous keratinocytes (CAK) have been heralded as a means to achieve more rapid closure of massive burn wounds. Despite the claimed benefits of this technology, we have failed to identify its positive impact on wound closure in extensively burned patients. Sixteen patients with a mean age of 29.7 years (range, 10-56 years) and a mean total body surface area burn of 68.2% (range, 42% 85%) underwent 22 applications of CAK supplied by a private laboratory. The keratinocyte grafts were applied to a mean of 15.9% of the body surface area (range, 4%-59%) at an average cost per patient of $43,705 (range, $9,800 to $161,000). The mean body surface area of definitive wound coverage by these grafts was 4.7% (range, 0%-18.6%). The mean length of hospitalization was 132 days (range, 50-275 days). The observed mortality was 12.5% (two patients). Our experience with this wound care approach has been assessed with respect to the extent of burn, the level of wound excision, and the site of CAK application. PMID- 8497001 TI - Acute ethanol intoxication increases the risk of infection following penetrating abdominal trauma. AB - Acute alcohol (ETOH) intoxication as a risk factor for infection in trauma victims to our knowledge has not been previously reported. To determine if ETOH intoxication increases infection risk we examined data from 365 patients with penetrating abdominal trauma who were enrolled in a multi-center antibiotic study. Ninety-four patients sustained an injury to a hollow viscus. To separate acute from chronic ETOH effects, infections were divided into two categories: (1) trauma related; infections caused by bacterial contamination at the time of injury, while blood alcohol level (BAL) was elevated. (2) nosocomial; infections caused by bacteria acquired during hospital stay, after BAL had normalized. A BAL > or = 200 mg/dL was associated with a 2.6-fold increase in trauma-related infections. There was no association between BAL and subsequent nosocomial infection. Since infection rates for intoxicated patients were not higher after BAL had normalized, acute rather than chronic effects of ETOH appear to be responsible. PMID- 8497002 TI - Mechanisms of endotoxin-induced intestinal injury in a hyperdynamic model of sepsis. AB - The goal of this study was to test the hypothesis that endotoxin-induced bacterial translocation is the result of a selective decrease in intestinal blood flow that causes an oxidant-mediated intestinal mucosal injury. To accomplish this goal, 116 instrumented rats receiving a nonlethal dose of endotoxin (5 mg/kg IP) or saline were studied. Organ blood flow and cardiac output were measured using the microsphere technique and intestinal permeability was measured both by the blood to luminal clearance of 51Cr-EDTA and by horseradish peroxidase. Cardiac output was higher in the endotoxin-treated group than in the saline group (76 +/- 12 versus 95 +/- 17 mL/min; p < 0.05). Although endotoxin induced a hyperdynamic state, blood flow to the distal ileum and cecum was selectively decreased by 35%-50% (p < 0.01), whereas blood flow to the rest of the intestine, spleen, pancreas, and liver was normal. Furthermore, blood flow to the ileal mucosa was decreased to a greater extent than to the remainder of the gut wall (p < 0.05). Small bowel permeability to 51Cr-EDTA was increased at sites of decreased blood flow (ileum) but not at sites of normal (jejunum) blood flow. Allopurinol, a competitive inhibitor of xanthine oxidase, ameliorated the endotoxin-induced decrease in ileal blood flow as well as the increase in ileal permeability. Thus these studies support the hypothesis that endotoxin-induced mucosal injury is the result of an ischemia reperfusion-mediated injury of the distal small intestine and cecum. PMID- 8497003 TI - Correlation of the local and systemic cytokine response with clinical outcome following thermal injury. AB - Eighty-eight patients with acute thermal injury were evaluated. Forty-eight hours after injury, TNF, IL-6, and IL-8 were significantly present in the systemic circulation, lung, normal skin, and thermally injured skin. The presence of TNF, IL-6, and IL-8 proteins in the lung, normal skin, and thermally injured skin were associated with TNF, IL-6, and IL-8 mRNA upregulation. Logistic regression analysis controlling for the Abbreviated Burn Severity Index demonstrated that the presence of IL-8 in the lung was associated with early pulmonary physiologic dysfunction (p = 0.006) and nosocomial pulmonary infection (p = 0.040). We conclude that acute thermal injury initiates an early systemic, lung, and skin response involving TNF, IL-6, and IL-8. The TNF, IL-6, and IL-8 protein present in the lung and skin in response to acute thermal injury are generated locally and do not originate from the systemic cytokine pool. The lung cytokine response to acute thermal injury may initiate local organ failure. PMID- 8497004 TI - Use of transesophageal echocardiography in the evaluation of traumatic aortic injury. AB - Indications for aortography following blunt chest trauma are broad and ill defined. This study prospectively assessed the role of transesophageal echocardiography (TEE) in the evaluation of suspected aortic injury. We used both TEE and aortography to evaluate 69 patients with suspected thoracic aortic injury. The studies were performed and interpreted by staff radiologists and cardiologists. The mean study time for TEE was 27 minutes, whereas the mean study time for aortography was 76 minutes (p < 0.05). No complications occurred with either procedure. Both TEE and aortography revealed no evidence of aortic injury in 61 patients. There was one false-positive aortogram. TEE identified seven aortic injuries; four were confirmed by aortography. One patient underwent thoracotomy and aortic repair based on TEE findings alone. Aortograms yielded false-negative results for two patients; one injury was confirmed at thoracotomy, the other at autopsy. TEE accurately predicted the presence or absence of aortic injury in each case, for a diagnostic sensitivity and specificity of 100%. TEE can be performed safely and efficiently on the multiple-injury patient. We conclude that TEE is useful in the evaluation of suspected aortic injury. PMID- 8497005 TI - Prospective evaluation of thoracoscopy for diagnosing diaphragmatic injury in thoracoabdominal trauma: a preliminary report. AB - Diagnosis of diaphragmatic injury (DI) can be difficult in patients with penetrating trauma because physical examination, computed tomographic scan, chest x-ray films, and diagnostic peritoneal lavage may miss these injuries. Mandatory exploration has been recommended because of the increased mortality associated with missed DI. Thoracoscopy was prospectively evaluated as a less invasive method for diagnosing DI in patients with penetrating trauma. Over a 14-month period, 14 patients were evaluated by thoracoscopy; video thoracoscopy was used in the last 9. Findings of thoracoscopy were confirmed by laparotomy or laparoscopy. Thoracoscopy correctly identified the presence or absence of DI in nine and five patients, respectively (all patients). Video thoracoscopy was easier and faster to perform than non-video thoracoscopy. This is the first reported series in which video thoracoscopy has been used for trauma. We found this procedure to be safe, accurate, and less invasive than laparotomy for diagnosing DI. PMID- 8497006 TI - Cardiac stapling in the management of penetrating injuries of the heart: rapid control of hemorrhage and decreased risk of personal contamination. AB - The resuscitation of patients with cardiopulmonary arrest from a penetrating injury of the heart requires emergency thoracotomy and control of hemorrhage. Suture control may be technically difficult in patients with large or multiple lacerations. Emergency cardiac suturing techniques expose the surgeon to the risk of a contaminated needle stick. After we determined that rapid control of hemorrhage from cardiac lacerations could be achieved in anesthetized sheep with the use of a standard skin stapler, the technique was applied in the clinical setting. Twenty-eight patients underwent emergency stapling of 33 cardiac lacerations at our institution from September 1987 to December 1991. Seventy-nine percent (22) of the patients sustained stab wounds, and 21% (6) were injured by gunshots. Fifty-eight percent (19) of the injuries involved the right ventricle, 27% (9) involved the left ventricle, 9% (3) involved the right atrium, and 6% (2) involved the left atrium. In 93% (26) of the patients, control of hemorrhage was achieved within 2 minutes of exposure of the injuries. Both patients in whom control could not be achieved had sustained large-caliber gunshot injuries. Fifteen (54%) of the patients survived, including one patient with two cardiac lacerations and another with three lacerations. Of the surviving patients, two had mild neurologic deficits. No personal contamination occurred related to the use of the stapler. We conclude (1) cardiac stapling is highly effective in the management of hemorrhage from penetrating injury, particularly in the setting of multiple cardiac lacerations; (2) the technique may not be effective with certain types of gunshot wounds; and (3) the use of the stapler for emergency cardiorrhaphy eliminates the risk of personal contamination from a needle stick. PMID- 8497007 TI - Penetrating cardiac wounds: prospective study of factors influencing initial resuscitation. AB - A prospective study of 66 consecutive patients with cardiac wounds seen over a 27 month period is reported. No patient was excluded. Patients were stratified by injury mechanism and by physiologic scoring at admission using the cardiovascular respiratory elements of the Trauma Score (CVRS). Admission cardiac rhythm was obtained in patients with a CVRS of 0 and a Glasgow Coma Scale (GCS) score of 3. Information concerning the anatomic extent of the cardiac wound, the presence or absence of tamponade, and the degree of injury to other structures was also collected prospectively. Seventy percent of the cardiac wounds were caused by gunshots. The probability of successful resuscitation was significantly related to mechanism of injury and physiologic condition on arrival. Among patients arriving with a CVRS of 0 and a GCS score of 3, survival correlated with cardiac rhythm. Pericardial tamponade did not prove to be an independent predictor of early survival. The presence of tamponade was statistically linked to the mechanism of injury. Transport by non-official conveyance was associated with a higher CVRS on arrival. Intoxication with alcohol or cocaine had no evident effect on resuscitation probability. PMID- 8497008 TI - A study of pneumatic antishock garments in severely hypotensive trauma patients. AB - The effectiveness of a pneumatic antishock garment (PASG) on severely hypotensive trauma patients (BP < or = 50 mm Hg) was studied using two data sets. The first included data from eight hospitals collected over 4 1/2 years; the second included 2 years of data from an additional eight hospitals. Data were collected by trained nurse abstractors whose interrater reliability was extremely high for AIS and ISS scoring. One hundred forty-two patients had blood pressures < 50 mm Hg. The PASG patients had a higher survival rate than non-PASG patients (Pr = 0.055). The PASG appeared to have the most effect on patients with abdominal injuries since no patient with such an injury survived unless a PASG was applied. Controlling for severity using the TRISS method, z scores indicated that the survival rate in the PASG group was significantly higher than expected whereas that in the non-PASG group was similar to that predicted; the same pattern was found when blunt injury and penetrating injury patients were analyzed separately. Improvement in survival among PASG patients occurred despite an average scene time that was 4.7 minutes longer than that for non-PASG patients. No improvement in survival among PASG versus non-PASG patients with blood pressures of 50-70 mm Hg or in those with blood pressures of 90 mm Hg or less was found. We conclude that the use of PASG in severely hypotensive patients (BP < or = 50) should be considered medically acceptable pending randomized controlled studies. PMID- 8497009 TI - Safety belt restraints and compartment intrusions in frontal and lateral motor vehicle crashes: mechanisms of injuries, complications, and acute care costs. AB - A 3-year prospective study examined 76 frontal (F) and 45 lateral (L) motor vehicle crash (MVC) patients with regard to seatbelt restraint use and occupant compartment contact and intrusion injuries. These 121 MVC victims with multiple injuries (39 belted [B] and 82 non-belted [NB]), admitted to a level I trauma center, were studied by accident reconstruction and medical data analysis. They had a MVC mean impact velocity (delta V) of 30 +/- 11 mph and an injury Severity Score of 29 +/- 12. Proper restraint use reduced brain injury in F MVCs (30% FB vs. 47% FNB) but had no effect in L MVCs (63% LB vs. 30% FB [p < 0.06]). Belt use did not protect against lung, liver, spleen, pelvis, or lower extremity (LE) injury. These appeared to be more a function of crash direction, with LE injuries higher in F crashes (p < 0.04) and pelvis injuries (p < 0.001) higher in L crashes. In FB crashes, however, properly used safety restraints were the primary cause of bowel or colon injuries (p < 0.006). Belts did not prevent thoracic or abdominal solid organ injuries in L crashes. Contact-intrusions (CI) of the car occupant compartment in F crashes were the main cause of brain (A-pillar), lung and liver (steering wheel and instrument panel), and LE (toepan) injuries; but in L crashes, side-door CI caused lung, aorta, liver, and pelvic injuries. In contrast, contact-only (CO) injuries of the steering assembly were mainly responsible for injuries to the lung, heart, and liver in F crashes, and side door CO for lung, liver, and spleen injuries in L crashes. Deaths and complications after injury were higher among F MVC occupants, or when delta V was > or = 30 mph. Hospital and professional costs reflect the complex care needed for victims of multiple injuries: FB, $99,000; FNB, $95,000; LB, $75,000; LNB, $79,000; total, $10.7 million. Present vehicle safety standards are not adequate, and structural design changes are needed to improve restraints and protect occupants from intrusion-related injuries. PMID- 8497010 TI - Catastrophic complication of simple cast treatment: case report. AB - We report the case of a 36-year-old man who developed a compartment syndrome after a minor ankle fracture was casted. The treatment was inadequately monitored and he subsequently developed the manifestations of a crush syndrome. This case demonstrates that relatively minor injuries can indeed be fatal if appropriate vigilance is not maintained. PMID- 8497011 TI - Heart rate, alveolar gases and blood lactate during synchronized swimming. AB - Heart rate, alveolar gas partial pressures and blood lactate (BLa) concentration were measured during synchronized swimming in six subjects. During upside-down breath-holding lasting 50 s, heart rate fell progressively from 98 +/- 14 to 70 +/- 7 beats min-1 (mean +/- S.D.). While breath-holding during the compulsory figures, the subjects' heart rate increased to 142 +/- 5 beats min-1 and then fell to 72 +/- 10 beats min-1. At the end of breath-holding, alveolar oxygen pressure had fallen significantly (60 mmHg), whereas alveolar carbon dioxide pressure showed only minor changes (48 mmHg). The increase in BLa concentration due to the execution of compulsory figures was approximately 1 mM; in the free routines, BLa concentration increased by 3.4 +/- 0.5 mM. The net energy cost of completing a compulsory figures lasting 45 s was 34.6 kJ. PMID- 8497012 TI - The effects of an acute bout of sleep on running economy and VO2 max. AB - Synchronized human sleep has been shown to decrease activation of the sympathetic nervous system, resulting in reduced levels of oxygen consumption. This is in direct conflict with sympathetic arousal, which coincides with the initiation of exercise. Although a considerable body of research has investigated the effects of sleep deprivation on exercise performance, the effects of an acute bout of sleep on exercise response have not been previously reported. This question appears relevant considering the occurrence of acute sleep bouts among athletes competing in prolonged multi-event competition (e.g. swimming, track and field). To investigate the effects of an acute bout of sleep on submaximal (running economy) and maximal oxygen consumption, seven male volunteers participated in a continuous, progressive treadmill test to volitional exhaustion immediately following a 1-h bout of sleep (SB) or no sleep (Control). The subjects served as their own controls and the order of trials was randomized. A MANOVA with repeated measures indicated no difference between groups for running economy or VO2 (P < 0.05). However, a significant interaction effect was observed in which SB resulted in greater running economy (lower VO2) through the first two stages of the protocol, while the control treatment yielded a greater economy throughout the remaining stages. While the implications of the findings are uncertain, they may indicate differences in psychological arousal or anxiety as a result of treatments or the possibility of a delayed sympathetic arousal in the early stages of exercise following sleep. PMID- 8497013 TI - Anthropometric profiles of elite male and female competitive sport rock climbers. AB - Over the past few years, competitive rock climbing--for a long time a popular sport in Europe--has increased in popularity in North America. An annual international World Cup competition circuit was started in 1988 which has shown growing success and a definite elite group of athletes has emerged. Descriptive anthropometric profiles of elite climbers have been unavailable. In order to fill this information void, 39 world-class climbers (21 males, 18 females) were assessed immediately prior to competition at an international World Cup sport climbing championship. All of the subjects tested were competition semi-finalists and, among these, seven males and six females advanced to the finals. The variables measured included age, years of climbing experience, height, body mass, height-weight ratio, sum of seven skinfolds, % body fat, fat-free mass, hand and arm volumes via plethysmography, average of right and left grip strengths, grip strength to body mass ratio (SMR), and climbing ability defined as the most difficult route climbed on lead. The results indicated that elite sport climbers are of small to moderate stature and exhibit very low % fat, moderate grip strength and high SMR when compared with other athletic groups. Values for the height-weight ratio and sum of seven skinfolds in the female finalists were very near those of the male finalists, which may indicate that reduction of body mass and % fat are primary adaptations in these female athletes. Climbing ability was predictable from SMR and % fat, though the R2 was low. PMID- 8497014 TI - Effect of diet on performance during recovery from intermittent sprint exercise. AB - Eighteen games players (9 males, 9 females) performed 30 maximum 6-sprints on a non-motorized treadmill. Each sprint was preceded by a 60-s jog at 40% maximum speed and was followed by a 54-s walk at 20% maximum speed. Thus, the entire test was of 60-min duration. The subjects were then randomly assigned to three groups and repeated the 1-h test 24 h later after consuming either a high, normal or low carbohydrate diet (79 +/- 3, 47 +/- 8, 12 +/- 1% CHO, respectively). During trial 1, mean power output declined from 653 +/- 131 to 600 +/- 158 W during the 30 sprints (P < 0.01) and power output was lower during trial 2 than during trial 1 (n = 18, P < 0.01). During trial 2, there were no differences in sprint performance between the dietary groups for the exercise test as a whole (trial 2 mean power lower than trial 1 by 0.2, 0.5 and 5.0% for the high, normal and low CHO groups, respectively; N.S.), but if only the first nine sprints are considered, then the high CHO group performed better than the low CHO group (P < 0.05). Blood lactate and glucose concentrations were lower during trial 2 than trial 1 by 4.5, 13.8 and 29.0% (lactate) and 14.9, 11.3 and 35.8% (glucose) for the high, normal and low CHO groups, respectively (both P < 0.01). Thus, both the metabolic responses to, and the performance of, maximum intermittent exercise were reduced when the test was repeated after 24 h recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497015 TI - Body size and shape: a longitudinal investigation of active and sedentary boys during adolescence. AB - The aims of the present study were to contrast the distance and velocity curves for height, body mass and somatotype between active (n = 33) and sedentary (n = 15) boys studied annually between 12 and 15 years. Raw measurements were rescaled and aligned according to peak velocity in height (PHV). The sedentary boys were taller up to and including PHV, active boys being taller after PHV (P > 0.05). The sedentary group had a PHV of 8.5 +/- 1.2 cm year-1 and the active group one of 9.5 +/- 1.5 cm year-1 (P < 0.05). Their ages at PHV were 14.1 +/- 0.8 and 14.2 +/- 0.9 years, respectively (P > 0.05). The active boys were lighter before PHV but heavier afterwards. Peak body mass velocities (PBMV) were larger for the active children (9.1 +/- 2.7 kg year-1) compared to the sedentary children (8.0 +/- 2.6 kg year-1) (P > 0.05). At PBMV, the active boys were aged 14.3 +/- 0.8 years and the sedentary boys 14.5 +/- 0.7 years (P > 0.05). The representative somatotype for the sedentary group was a mesomorphic ectomorph. For the active group, ectomorphic mesomorphs and mesomorphic ectomorphs were the most prominent. The sedentary children (overall mean 2.4-3.4-4.7) showed an increase in endomorphy and a decrease in mesomorphy and ectomorphy. In contrast, the active children (overall mean 2.3-3.9-4.0) demonstrated reduced endomorphy with mesomorphy and ectomorphy remaining fairly uniform. Velocities showed mesomorphy to be the most stable component in both groups (-3.0 to +0.1 units year-1). Endomorphy and ectomorphy fluctuated to a greater extent but never quite reached a velocity of one-half unit a year. Whole somatotype analyses identified significant differences between groups at PHV (P < 0.05), individual component analyses at PHV and +1 year PHV (P < 0.05). PMID- 8497016 TI - Fingertip and venous blood lactate concentration in response to graded treadmill exercise. AB - Fingertip and venous blood lactate concentrations were determined pre-exercise and after 4-min bouts of treadmill running at 2.69, 3.13, 3.58 and 4.03 m s-1 in 14 normal healthy volunteers. A 1-min rest period intervened each exercise period, and was used for the simultaneous sampling of fingertip and venous blood. Compared to pre-exercise, fingertip and venous blood lactate (BLa) concentrations increased significantly (P < 0.05) in a progressive pattern with increasing exercise intensity. Fingertip BLa concentrations were significantly higher (P < 0.05) than venous blood prior to exercise and in response to all four running speeds. Treadmill speed, heart rate and oxygen consumption were significantly lower (P < 0.05) at a BLa concentration of 4 mM when estimated from fingertip blood as compared with venous blood. These results indicate that differences between fingertip and venous blood exist during treadmill exercise and should be considered when lactate determination is employed as a criterion to evaluate and predict performance and when used as a training guide to standardize exercise intensity. PMID- 8497017 TI - Inter-limb interactions and constraints in the expression of maximum force: a review, some implications and suggested underlying mechanisms. AB - Human motor action in both sporting and industrial situations involves complex movement patterns that require the concurrent activation of more than one unit of the motor system. This paper is about one aspect of how different muscle groups affect each other when they are activated in unison. Twenty years of research suggests that the maximum force-generating capacity of human muscles varies according to whether they contract alone or with other muscles. An example of this is the 'bilateral deficit' phenomenon (Ohtsuki, 1983), whereby the force produced when individuals perform simultaneous bilateral contractions of homologous limbs is less than the sum of the forces produced when each of the limbs contracts alone. The implications of investigations examining force-related patterns of inhibition in multi-limb action have been largely ignored and no serious attempt has hitherto been made to establish a theoretical framework within which to accommodate the findings. This paper reviews literature addressing the question of inter-limb inhibition in the expression of maximum force and discusses some of the implications that arise. A proposal is made that inter-limb interference can be accounted for in terms of the neural interconnectedness of cerebral control areas and suggestions made to show how the findings of previous research can be accommodated within contemporary neurobehavioural models of human performance. PMID- 8497018 TI - The effect of high- and low-intensity warm-up on the physiological responses to a standardized swim and tethered swimming performance. AB - This investigation was conducted to determine the effect of high- and low intensity warm-ups on physiological responses, lactate accumulation, and high intensity freestyle and tethered swimming performance. Ten male collegiate swimmers were tested for maximal oxygen uptake (VO2 max) followed by two series of three warm-up protocols performed in a randomized order at least 2 days apart. The warm-up protocols were: (1) no warm-up (NWU), (2) a 366-m swim at 70% VO2 max (LWU) and (3) four 46-m swims at 1-min intervals at a speed corresponding to 110% VO2 max (HWU). Five minutes after each warm-up in the first series, the swimmers swam a 183-m standardized freestyle swim at a velocity corresponding to 110% VO2 max, and 5 min after each warm-up in the second series the swimmers completed a tethered swim to exhaustion with a weight attached to the tether to elicit fatigue at about 2 min. Three minutes after each warm-up and 3 min after each standardized and tethered swim, a finger-prick blood sample for lactate measurement was obtained. Heart rate and VO2 were also measured during the warm up and the standardized and tethered swims. The performance times in the tethered swim were not significantly different between the three conditions (116.8 +/- 46.8, 137 +/- 53.3 and 122.94 +/- 37.2 s for the NWU, LWU and HWU, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497019 TI - The self-efficacy-performance link in maximum strength performance. AB - To examine whether manipulating self-efficacy affects strength performance on a bench press, and to see if these situation-specific changes would affect levels of physical self-efficacy, 24 undergraduates untrained in weightlifting were randomly assigned to three groups: 'light', who lifted less weight than they believed; 'heavy', who lifted more weight than they believed; and control, for whom there was no manipulation. Self-efficacy measures were taken before and after the manipulation. Physical self-efficacy was measured using the Physical Self-Efficacy Scale (PSE). 'Light' subjects lifted significantly greater increases in weight than the other subjects. 'Heavy' subjects significantly decreased self-efficacy following the manipulation. Initial self-efficacy was found to be a significant predictor of baseline maximum, while manipulated self efficacy was significant for performance change. The PSE scores did not change pre- to post-study. The results suggest that self-efficacy is a situation specific construct which can be manipulated, and which relates to both past performance experience and future performance. PMID- 8497020 TI - Imagery effects on the performance of skilled and novice soccer players. AB - The purpose of this study was to investigate the effect of an imagery training programme on the performance of a soccer task by skilled and novice players. An initial assessment of performance on the soccer task was undertaken, and then 22 skilled and 22 novice players were equally and randomly assigned to either a control or an experimental group. The experimental group was given an imagery training programme consisting of both visual and kinaesthetic imagery, and in which both internal and external imagery perspectives were included. The programme lasted 6 weeks, with the subjects attending bi-weekly sessions of approximately 15 min each. The control group developed a competitive strategy that was totally unrelated to the performance task. Similar to the experimental group, the controls did this over a 6-week period, attending bi-weekly sessions of 15 min duration. Two performance measures were recorded--response time (i.e. the time to complete the soccer task) and performance accuracy (i.e. errors in performing the soccer task recorded in the form of time penalties). Performance on the post-test as measured by response time revealed a significant improvement for both the skilled and novice players in the imagery group. The control group failed to show any such improvement. No effects were found for performance accuracy. PMID- 8497021 TI - Follow-up sonography in suspected acalculous cholecystitis: preliminary clinical experience. AB - Fourteen adult patients with clinically suspected AAC and inconclusive initial sonograms underwent follow-up sonography within 24 hours. Eight patients had initial studies demonstrating a normal thickness of the gallbladder wall. Four of these patients demonstrated progressive thickening of the gallbladder wall on follow-up scans and were diagnosed as having AAC. In three of these patients AAC was proved at surgery, and the remaining patient improved clinically after percutaneous cholecystostomy. Four other patients with normal gallbladder wall thickness on both the initial and follow-up sonograms had benign clinical follow up results without evidence of AAC. The remaining six patients had a thickened gallbladder on the initial sonogram. In one of these patients, the gallbladder wall thickening resolved on follow-up sonography. In the remaining five patients the gallbladder wall thickening did not change. Four of these patients had benign follow-up results but one patient was found to have AAC at surgery. Follow-up sonography may be helpful to confirm AAC if there is progressive edema of the gallbladder wall. A normal gallbladder wall on an initial study does not exclude early AAC. Thickening of the gallbladder wall on initial studies still remains a problem and other ancillary criteria must be used to establish the diagnosis of AAC. PMID- 8497022 TI - The AIUM/ACR antepartum obstetrical sonographic guidelines: expectations for detection of anomalies. AB - A survey was sent to 52 physicians considered experts in obstetrical sonography asking them to comment on the probability of observing various fetal abnormalities when the AIUM/ACR guidelines for a level one obstetrical sonogram were followed. Although definite trends were noted in several areas, there was much diversity in opinion concerning what should or should not be seen when the guidelines were followed. Given the fairly specific nature of the AIUM/ACR guidelines, we were uncertain why the responses were not in more uniform agreement. PMID- 8497023 TI - Fetal nonmuscular soft tissue: a prenatal assessment. AB - In this study, the fetal nonmuscular soft tissue is evaluated prenatally in 52 uncomplicated singleton pregnancies at 36 weeks of gestation or later. The means and standard deviations of the NMST at the midarm region and the ratio of NMST to HL are 6.0 +/- 1.0 mm and 0.08 +/- 0.02, respectively. No correlation was seen between the NMST and birth weight. PMID- 8497024 TI - Use of color Doppler ultrasonography (CDU) in the diagnosis of scrotal pathology of uncertain etiologic basis. PMID- 8497025 TI - Partial multiseptate gallbladder: sonographic appearance. AB - Multiseptate gallbladder, a rare congenital anomaly, is characterized by the presence of multiple thin septa dividing the gallbladder lumen into various sized chambers, often with a honeycomb appearance. In nearly all cases described previously, the entire gallbladder lumen was traversed by the septa. We describe three children, ages 3, 9, and 16 years, with sonographic features of multiseptate gallbladder, in which the septa were confined to the body and neck of the gallbladder in two, and to the fundus in one. The CT features of the anomaly also are described in one patient. PMID- 8497026 TI - The foramen magnum: the underutilized acoustic window to the posterior fossa. AB - Visualization of the posterior fossa during neonatal cranial sonography through the anterior fontanelle can at times be limited. To improve visualization of the posterior fossa, the foramen magnum was used as an acoustic window. Scans through the foramen magnum were obtained in addition to routine scans via the anterior fontanelle in 21 preterm infants. A subjective and retrospective evaluation was performed comparing clarity and definition of posterior fossa structures using the anterior fontanelle and foramen magnum. Images of the fourth ventricle, pons, vermis, cerebellar hemispheres, and cisterna magna were considered superior in clarity and definition when obtained via the foramen magnum. The tentorium was visualized equally well with both windows. Foramen magnum scanning demonstrated improved clarity of two Dandy-Walker variants in comparison to anterior fontanelle scanning. The use of the foramen magnum in addition to other acoustic windows can improve perceived clarity and definition of posterior fossa structures and aid in the detection of abnormalities and anomalies occurring in this location. PMID- 8497027 TI - Focal and diffuse increased echogenicity in the renal parenchyma in patients with sickle hemoglobinopathies--an observation. AB - Eleven patients with sickle hemoglobinopathies undergoing sonographic examinations for reasons unrelated to renal parenchymal disease were incidentally noted to have increased echogenicity in the central portion of the renal parenchyma. This appearance was observed to be a continuum, with some cases showing focally hyperechoic medullary pyramids at one extreme and other cases showing a diffusely echogenic central parenchymal region relative to a thin band of hypoechoic cortical or peripheral parenchyma at the other extreme. The finding of hyperechoic medullae of the kidneys has been reported in patients having conditions associated with hyperuricemia, medullary nephrocalcinosis, or hypokalemia. This sign has not been commonly reported as a finding in patients with sickle syndrome. The thin hypoechoic rim of cortical parenchyma relative to a more echogenic central parenchyma has not been commented on previously. PMID- 8497028 TI - Doppler sonographic measurement of phasic renal artery blood flow velocity in patients with chronic glomerulonephritis. AB - The phasic arterial blood flow velocity at the renal hilus was measured by Doppler sonography in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Doppler velocity waveform was analyzed to give peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). Color Doppler sonography facilitated the detection of blood flow and permitted the measurement of absolute blood flow velocity, which previously had been difficult to determine. These results suggest that renal arterial blood flow as detected by Doppler ultrasonography may be useful for noninvasive, direct, rapid, and simple evaluation of renal function, although various modifying factors also need to be considered. PMID- 8497029 TI - Color Doppler detection of a breast perilobular hemangioma. PMID- 8497030 TI - The use of color flow Doppler in the diagnosis of fetal hepatic hemangioma. PMID- 8497031 TI - Duplex sonographic detection of ascending pharyngeal artery arising from the internal carotid artery and supplying a dural arteriovenous malformation. PMID- 8497032 TI - Echogenicity of the fetal bowel due to gas accumulation. PMID- 8497033 TI - In utero detection of fetal cataracts. PMID- 8497034 TI - Candida brain abscess: a sonographic mimicker of intracranial hemorrhage. PMID- 8497035 TI - Case of the day. Presacral cystic teratoma. PMID- 8497036 TI - Case of the day. Angioblastic meningioma. PMID- 8497037 TI - Case of the day. Hemobilia: intraluminal gallbladder hematoma. PMID- 8497038 TI - Case of the day. Benign cystic teratoma (dermoid cyst) of the left ovary. PMID- 8497039 TI - Case of the day. Pentalogy of Cantrell. PMID- 8497040 TI - Case of the day. Renal vein and inferior vena cava thrombosis in a newborn. PMID- 8497041 TI - Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. AB - A model is proposed for the three-dimensional structure of the paramyxovirus hemagglutinin-neuraminidase (HN) protein. The model is broadly similar to the structure of the influenza virus neuraminidase and is based on the identification of invariant amino acids among HN sequences which have counterparts in the enzyme active center of influenza virus neuraminidase. The influenza virus enzyme-active site is constructed from strain-invariant functional and framework residues, but in this model of HN, it is primarily the functional residues, i.e., those that make direct contact with the substrate sialic acid, which have identical counterparts in neuraminidase. The framework residues of the active site are different in HN and in neuraminidase and appear to be less strictly conserved within HN sequences than within neuraminidase sequences. PMID- 8497042 TI - Role of conserved glycosylation sites in maturation and transport of influenza A virus hemagglutinin. AB - The role of three N-linked glycans which are conserved among various hemagglutinin (HA) subtypes of influenza A viruses was investigated by eliminating the conserved glycosylation (cg) sites at asparagine residues 12 (cg1), 28 (cg2), and 478 (cg3) by site-directed mutagenesis. An additional mutant was constructed by eliminating the cg3 site and introducing a novel site 4 amino acids away, at position 482. Expression of the altered HA proteins in eukaryotic cells by a panel of recombinant vaccinia viruses revealed that rates and efficiency of intracellular transport of HA are dependent upon both the number of conserved N-linked oligosaccharides and their respective positions on the polypeptide backbone. Glycosylation at two of the three sites was sufficient for maintenance of transport of the HA protein. Conserved glycosylation at either the cg1 or cg2 site alone also promoted efficient transport of HA. However, the rates of transport of these mutants were significantly reduced compared with the wild type protein or single-site mutants of HA. The transport of HA proteins lacking all three conserved sites or both amino-terminally located sites was temperature sensitive, implying that a polypeptide folding step had been affected. Analysis of trimer assembly by these mutants indicated that the presence of a single oligosaccharide in the stem domain of the HA molecule plays an important role in preventing aggregation of molecules in the endoplasmic reticulum, possibly by maintaining the hydrophilic properties of this domain. The conformational change observed after loss of all three conserved oligosaccharides also resulted in exposure of a normally mannose-rich oligosaccharide at the tip of the large stem helix that allowed its conversion to a complex type of structure. Evidence was also obtained suggesting that carbohydrate-carbohydrate interactions between neighboring oligosaccharides at positions 12 and 28 influence the accessibility of the cg2 oligosaccharide for processing enzymes. We also showed that terminal glycosylation of the cg3 oligosaccharide is site specific, since shifting of this site 4 amino acids away, to position 482, yielded an oligosaccharide that was arrested in the mannose-rich form. In conclusion, carbohydrates at conserved positions not only act synergistically by promoting and stabilizing a conformation compatible with transport, they also enhance trimerization and/or folding rates of the HA protein. PMID- 8497043 TI - Molecular comparison of the structural proteins encoding gene clusters of two related Lactobacillus delbrueckii bacteriophages. AB - Virulent phage LL-H and temperate phage mv4 are two related bacteriophages of Lactobacillus delbrueckii. The gene clusters encoding structural proteins of these two phages have been sequenced and further analyzed. Six open reading frames (ORF-1 to ORF-6) were detected. Protein sequencing and Western immunoblotting experiments confirmed that ORF-3 (g34) encoded the main capsid protein Gp34. The presence of a putative late promoter in front of the phage LL-H g34 gene was suggested by primer extension experiments. Comparative sequence analysis between phage LL-H and phage mv4 revealed striking similarities in the structure and organization of this gene cluster, suggesting that the genes encoding phage structural proteins belong to a highly conservative module. PMID- 8497044 TI - Truncations of the simian immunodeficiency virus transmembrane protein confer expanded virus host range by removing a block to virus entry into cells. AB - We have investigated how truncation of the cytoplasmic domain of the transmembrane (TM) glycoprotein of simian immunodeficiency virus (SIV) modulates the host range of this virus. Termination codons were introduced into the env gene of SIVmac239 which resulted in the truncation of the transmembrane protein from a wild-type 354 amino acids (TM354) to 207 (TM207) and 193 (TM193) amino acids. Expression of the wild-type and mutant env genes from a simian virus 40 based vector resulted in normal biosynthesis and processing of the glycoproteins to gp130 and gp41 or the truncated TM proteins (gp28 and gp27). When expressed on the surface of COS-1 cells, all three glycoproteins mediated fusion of both CEMX174 and HUT78 cells. Virions containing the wild-type and mutant glycoproteins were capable of efficient replication in macaque peripheral blood lymphocytes and CEMX174 cells; in contrast, only virions that contained TM207 were capable of rapid infection of HUT78 cells. Both truncated glycoproteins were capable of efficiently mediating infection of both CEMX174 and HUT78 cells by an env-deficient human immunodeficiency virus. The wild-type SIV glycoprotein, however, was unable to mediate human immunodeficiency virus infection of HUT78 cells when assayed with this system. An analysis of the protein composition of SIV released from infected CEMX174 cells showed that the mutant virions contained significantly higher levels of glycoprotein compared with the wild type. These results demonstrate that truncation of the SIV cytoplasmic domain removes a block at the level of glycoprotein-mediated virus entry into HUT78 cells and points to a role for glycoprotein density in determining virus tropism. PMID- 8497045 TI - Human papillomavirus type 18 E7 protein requires intact Cys-X-X-Cys motifs for zinc binding, dimerization, and transformation but not for Rb binding. AB - Human papillomavirus type 18 (HPV-18) E7 proteins bind zinc through Cys-X-X-Cys repeats located at the C terminus of the protein. In order to examine the role of these cysteine motifs in E7 function, we expressed the HPV-18 E7 protein in bacteria and found that purified E7 forms a dimer through interactions with zinc. Mutants with single mutations within the Cys-X-X-Cys motifs bound a reduced level of zinc in a zinc blot assay, while a double mutant lost all zinc-binding activity. When expressed in vivo, none of the mutants cooperated with an activated ras oncogene to transform primary rat embryo fibroblasts, but all mutants retained nearly wild-type Rb-binding activity. The results indicate that the cysteine motifs play an important role in transformation by HPV-18 E7 but do not contribute to Rb binding. PMID- 8497046 TI - Endogenous expression of E1A in human cells enhances the effect of adenovirus E3 on class I major histocompatibility complex antigen expression. AB - Group C human adenovirus (Ad) serotypes (e.g., Ad type 2 [Ad2] and Ad5) cause persistent infections in humans. One explanation for Ad persistence is an ineffective cytotoxic T-lymphocyte response due to diminished cell surface expression of class I major histocompatibility antigen (MHC Ag) on Ad-infected cells, an effect mediated by the Ad E3 19-kDa glycoprotein (E3 effect). However, we previously reported that, except for the Ad5 E1-transformed human cell line 293, a variety of human lymphoid, epithelial, and fibroblastic cells are resistant to the E3 effect during Ad5 infection (J. M. Routes and J. L. Cook, J. Immunol. 144:2763-2770, 1990). The present study tested the hypothesis that endogenous expression of E1A proteins in 293 cells sensitizes cells to this E3 effect, resulting in an enhanced downregulation of surface class I MHC Ag expression following Ad5 infection. Human epithelial and fibroblastic cells expressing E1A gene products for at least 72 h exhibited an enhanced E3 effect following Ad5 infection that was independent of baseline levels of surface class I MHC Ag expression and of E1A induction of E3 19-kDa glycoprotein expression. There was a direct correlation between the level of endogenous E1A expressed and the magnitude of the E3 effect. We postulate that the in vivo existence of cells stably expressing either E1A proteins or E1A-like activities in the microenvironment of Ad5 infection provides a reservoir of Ad-infected cells that is relatively protected from the virus-specific cytotoxic T-lymphocyte response, thereby favoring Ad persistence in humans. PMID- 8497047 TI - Hybrid human immunodeficiency virus Gag particles as an antigen carrier system: induction of cytotoxic T-cell and humoral responses by a Gag:V3 fusion. AB - In attempts to increase the immunogenicity of recombinant antigens, a number of particulate antigen presentation systems have been developed. In this study, we used human immunodeficiency virus Gag particles as carriers for the human immunodeficiency virus envelope V3 region. Gag:V3 fusion proteins were expressed from baculovirus expression vectors; they migrated to the insect cell membrane and budded from the cells as hybrid particles. An immunization study carried out with rats showed that the particles elicited a strong anti-Gag antibody response and a weak antibody response to the V3 region. A strong anti-V3 cytolytic T-cell response was elicited in immunized mice. These data show that retroviral Gag particles can be used as antigen presentation vehicles. PMID- 8497048 TI - Regulated splicing of adenovirus type 5 E4 transcripts and regulated cytoplasmic accumulation of E4 mRNA. AB - The E4 gene of human type C adenoviruses has been shown previously to give rise to an array of mRNAs via differential splicing. In this study, the pattern of expression of these mRNAs during lytic infection was examined, and two distinct temporal classes were defined. mRNAs of the early class were distinguished from those of the late class by the presence, in the early class, of a sequence in the 3' half of the mRNA that was removed as an intron in the late class. A single mRNA of the late class was found to show a strong dependence on the presence of the 55-kDa protein from region E1b and the open reading frame 6 protein from region E4 for its normal cytoplasmic accumulation. One feature of this mRNA that distinguishes it from other E4 mRNAs expressed at late times is the retention within it of an intron from the 5' half of E4; it may therefore be recognized as incompletely spliced by the host cell and retained in the nucleus. It is proposed that the E1b 55-kDa/E4 open reading frame 6 protein complex facilitates accumulation of this mRNA by overcoming this retention mechanism. PMID- 8497049 TI - Identification of tRNAs incorporated into wild-type and mutant human immunodeficiency virus type 1. AB - We have identified the tRNAs which are incorporated into both wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1IIIB) produced in COS-7 cells transfected with HIV-1 proviral DNA and mutant, noninfectious HIV-1Lai particles produced in a genetically engineered Vero cell line. The mutant proviral DNA contains nucleotides 678 to 8944; i.e., both long terminal repeats and the primer binding site are absent. As analyzed by two-dimensional polyacrylamide gel electrophoresis, both mutant and wild-type HIV-1 contain four major-abundance tRNA species, which include tRNA(1,2Lys), tRNA(3Lys) (the putative primer for HIV 1 reverse transcriptase) and tRNA(Ile). Identification was accomplished by comparing the electrophoretic mobilities and RNase T1 digests with those of tRNA(3Lys) and tRNA(1,2Lys) purified from human placenta and comparing the partial nucleotide sequence at the 3' end of each viral tRNA species with published tRNA sequences. Thus, the absence of the primer binding site in the mutant virus does not affect tRNA(Lys) incorporation into HIV-1. However, only the wild-type virus contains tRNA(3Lys) tightly associated with the viral RNA genome. The identification of the tightly associated tRNA as tRNA(3Lys) is based upon an electrophoretic mobility identical to that of tRNA(3Lys) and the ability of this RNA to hybridize with a tRNA(3Lys)-specific DNA probe. In addition to the four wild-type tRNA species, the mutant HIV-1-like particle contains two tRNA(His) species and three tRNA-sized species that we have been unable to identify. Their absence in wild-type virus makes it unlikely that they are required for viral infectivity. PMID- 8497050 TI - Characterization of a temperature-sensitive influenza B virus mutant defective in neuraminidase. AB - ts5, a temperature-sensitive mutant of influenza B virus, belongs to one of seven recombination groups. When the mutant infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious virus was produced at very low levels compared with the yield at the permissive temperature (32 degrees C) and hemagglutinating and enzymatic activities were undetectable. However, viral protein synthesis and transport of hemagglutinin (HA) and neuraminidase (NA) to the cell surface were not affected. The NA was found as a monomer within cells even at 32 degrees C, in contrast to wild-type virus NA, existing mostly as an oligomer, but the mutant had oligomeric NA, like the wild-type virus. Its enzymatic activity was more thermolabile than that of wild-type virus. Despite the low yield, large aggregates of progeny virus particles were found to accumulate on the cell surface at the nonpermissive temperature, and these aggregates were broken by treatment with bacterial neuraminidase, with the concomitant appearance of hemagglutinating activity, suggesting that NA prevents the aggregation of progeny virus by removal of neuraminic acid from HA and cell receptor, allowing its release from the cells. Further treatment with trypsin resulted in the recovery of infectivity. When bacterial NA was added to the culture early in infection, many hemagglutinable infectious virus was produced. We also suggest that the removal of neuraminic acid from HA by NA is essential for the subsequent cleavage of HA by cellular protease. Nucleotide sequence analysis of RNA segment 6 revealed that ts5 encoded five amino acid changes in the NA molecule but not in NB. PMID- 8497051 TI - Reduced cell surface expression of processed human immunodeficiency virus type 1 envelope glycoprotein in the presence of Nef. AB - nef genes from two laboratory grown human immunodeficiency virus type 1 (HIV-1) strains and from two proviruses that had not been propagated in vitro were introduced into CD4+ lymphoblastoid CEM cells. The stable expression of all four Nef proteins was associated with an almost complete abrogation of CD4 cell surface localization. The consequences of the presence of Nef on gp160 cleavage, gp120 surface localization, and envelope-induced cytopathic effect were examined in CEM cells in which the HIV-1 env gene was expressed from a vaccinia virus vector. The presence of Nef did not modify the processing of gp160 into its subunits but resulted in a significant decrease of cell surface levels of gp120, associated with a dramatic reduction of the fusion-mediated cell death. Surface levels of mutant envelope glycoproteins unable to bind CD4 were not altered in Nef-expressing cells, suggesting that the phenomenon was CD4 dependent. The intracellular accumulation of fully processed envelope glycoproteins could significantly delay the cytopathic effect associated with envelope surface expression in HIV-infected cells and may be relevant to the selective advantage associated with Nef during the in vivo infectious process. PMID- 8497052 TI - Ribonucleoprotein complexes of hepatitis delta virus. AB - Human hepatitis delta virus (HDV) is a subviral satellite agent of hepatitis B virus (HBV). The envelope proteins of HDV are provided by the helper virus, HBV, but very little is known about the internal structure of HDV. The particles contain multiple copies of the delta antigen and an unusual RNA genome that is small, about 1,700 nucleotides in length, single stranded, and circular. By using UV cross-linking, equilibrium density centrifugation, and immunoprecipitation, we obtained evidence consistent with the interpretation that delta antigen and genomic RNA form a stable ribonucleoprotein (RNP) complex within the virion. Furthermore, electron-microscopic examination of the purified viral RNP revealed a roughly spherical core-like structure with a diameter of 18.7 +/- 2.5 nm. We also isolated HDV-specific RNP structures from the nuclei of cells undergoing HDV genome replication; both the genome and antigenome (a complement of the genome) of HDV were found to be in such complexes. From the equilibrium density analyses of the viral and nuclear RNPs, we were able to deduce the number of molecules of delta antigen per molecule of HDV RNA. For virions, this number was predominantly ca. 70, which was larger than for the nuclear RNPs, which were more heterogeneous, with an average value of ca. 30. PMID- 8497053 TI - Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. AB - Vaccinia virus strains vary considerably in the amounts of extracellular enveloped virus (EEV) that they release from infected cells. The IHD-J strain produces up to 40 times more EEV than does the related WR strain and consequently generates elongated comet-shaped virus plaques instead of sharply defined round ones in susceptible monolayer cells under liquid medium. The difference in EEV formation is due to the retention of enveloped WR virions on the cell surface (R. Blasco and B. Moss, J. Virol. 66:4170-4179, 1992). By using WR and IHD-J DNA fragments for marker transfer and analyzing the progeny virus by the comet formation assay, we determined that gene A34R and at least one other gene regulate the release of cell-associated virions. Replacement of the A34R gene of WR with the corresponding gene from IHD-J increased the amount of EEV produced by 10-fold and conferred the ability to form distinctive comet-shaped plaques. Gene A34R encodes an EEV-specific glycoprotein with homology to C-type animal lectins (S.A. Duncan and G.L. Smith, J. Virol. 66:1610-1621, 1992). The nucleotide sequences of the A34R genes of WR and IHD-J strains differed in six positions, of which four were silent. One of the codon mutations (Lys-151-->Glu), which is located in the putative carbohydrate recognition domain, was sufficient to transfer a comet-forming phenotype to WR virus. These data indicate that the A34R encoded glycoprotein is involved, through its lectin homology domain, in the retention of progeny virus on the surface of parental cells and raise the possibility that the protein also has a role in virus attachment to uninfected cells. PMID- 8497054 TI - Interchangeability of the adsorption proteins of bacteriophages Ff and IKe. AB - The wild-type adsorption protein (g3p) of filamentous phage IKe cannot be exchanged with its analogous protein in the related Ff (M13, fd, and f1) phage particles. Deletion mutants of the protein, however, are assembled into Ff phage particles. These hybrid Ff phage particles bearing deleted IKe g3p attach to N pili, thus conserving the host attachment property of the protein but not its infection-initiating function. This means that the attachment specificity is determined by IKe g3p independently of other phage components in contact with it. Infection initiation function, the process in which phage DNA is released into the host, in contrast seems to require either more complex structural features of the protein (for example, a certain oligomeric structure) provided only in the original particle, or a concerted action of g3p with another particle component, not replaceable by its homologous counterpart in the related phage. PMID- 8497055 TI - Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. AB - Viral RNA was extracted from plasma samples collected from five individuals during the period of viremia before seroconversion in primary infection with human immunodeficiency virus type 1 (HIV-1) and amplified by polymerase chain reaction. Nucleotide sequence analysis of amplified DNA from the V3 and V4 hypervariable regions indicated that the initial virus population of each acutely infected individual was completely homogeneous in sequence. No intrasample variability was found among the 44,090 nucleotides sequenced in this region of env, contrasting with the high degree of variability normally found in seropositive individuals. Paradoxically, substantial sequence variability was found in the normally high conserved gag gene (encoding p17) in most of the preseroconversion samples. The diversity of p17 sequences in samples that were homogeneous in V3 and V4 can most readily be explained by the existence of strong selection for specific env sequences either upon transmission or in the interval between exposure and seroconversion in the exposed individual. Evidence that localizes the selected region upon transmission to V3 is provided by the similarity or identity of V3 loop sequences in five individuals with epidemiologically unrelated HIV-1 infections, while regions flanking the V3 loop and the V4 hypervariable region were highly divergent. The actual V3 sequences were similar to those associated with macrophage tropism in primary isolates of HIV, irrespective of whether infection was acquired by sexual contact or parenterally through transfusion of contaminated factor VIII. Proviral DNA sequences in peripheral blood mononuclear cells remained homogeneous in the V3 and V4 regions (and variable in p17gag) for several months after seroconversion. The persistence of HIV sequences in peripheral blood mononuclear cells identical to those found at primary infection in the absence of continued virus expression provides an explanation for the previously observed differences in the composition of circulating DNA and RNA populations in sequential samples from seropositive individuals. PMID- 8497056 TI - Experimental transmission of human hepatitis delta virus to the laboratory mouse. AB - Human hepatitis delta virus (HDV), obtained from the serum of an experimentally infected woodchuck, was injected into either the peritoneal cavity or the tail vein of both adult CB17 mice and mice with a severe combined immunodeficiency (CB17-scid mice). Three lines of evidence indicated that the virus was able to reach the liver and infect hepatocytes: (i) the amount of HDV genomic RNA detected in the liver by Northern (RNA) analysis increased during the first 5 to 10 days postinoculation, reaching a peak that was about threefold the amount in the original inoculum; (ii) also detected in the liver was the viral antigenomic RNA, which is complementary to the genomic RNA found in virions, and is diagnostic for virus replication; and (iii) by immunoperoxidase staining of liver sections, the delta antigen was detected in the nuclei of scattered cells identifiable as hepatocytes. In all of the mice, clearance of the infection occurred between 10 and 20 days after inoculation. The half-life for clearance was about 3 days in CB17-scid mice, indicating that clearance of infection did not involve a T- and B-cell-dependent immune response. Cell-to-cell spread of the initial infection was not detected. One possible interpretation of our results is that HDV infection of hepatocytes is directly cytopathic. Also, the results imply that chronic infection of the liver in humans may require continuous spread of virus within the liver. Alternatively, HDV in the absence of helper virus may be unable to cause a chronic infection of hepatocytes in vivo. PMID- 8497057 TI - Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro. AB - The adenovirus precursor to the terminal protein (pTP), expressed in a vaccinia virus expression system or in native adenovirus, was assayed for its ability to interact with the nuclear matrix. Biochemical function was measured by determining the relative amount of pTP protein or of adenovirus DNA that remained associated with the nuclear matrix after extensive washing. pTP was retained on the matrix whereas beta-galactosidase was not, as assayed by quantitative immunoblot analysis. Nuclear matrix isolated from adenovirus-infected HeLa cells retained bound adenovirus DNA even when washed with 1 M guanidine hydrochloride; this interaction could be inhibited by added purified pTP protein. Analogous experiments with matrix isolated from HeLa cells infected with a recombinant vaccinia virus that expressed pTP showed a similar retention of pTP protein; this association could also be inhibited by added pTP protein. Binding of pTP to nuclear matrix isolated from uninfected cells was saturable, with an apparent Kd of 250 nM and an estimated 2.8 x 10(6) sites for pTP binding per cell nucleus. The association of pTP with matrix is postulated to help direct adenovirus replication complexes to the appropriate locale within the nucleus. PMID- 8497058 TI - Cross-reactive lysis of human targets infected with prototypic and clinical human immunodeficiency virus type 1 (HIV-1) strains by murine anti-HIV-1 IIIB env specific cytotoxic T lymphocytes. AB - To evaluate the ability of murine anti-human immunodeficiency virus type 1 (HIV 1) IIIB env cytotoxic T lymphocytes (CTL) to recognize and lyse HIV-1-infected cells, we have constructed a human cell line (Hu/Dd) expressing both the CD4 receptor and the murine H-2Dd major histocompatibility complex (MHC) class I protein. This cell line can be productively infected with HIV-1 and can also function as a target for murine CD8+, class I MHC-restricted CTL directed against the envelope glycoprotein of HIV-1 IIIB. The ability of BALB/c anti-HIV-1 IIIB env CTL to specifically recognize and lyse Hu/Dd target cells infected with divergent HIV-1 strains was tested by using both prototypic and clinical HIV-1 strains. CTL generated by immunization of mice with syngeneic cells expressing either the native or V3 loop-deleted (delta V3) envelope glycoprotein from HIV-1 IIIB were able to recognize and specifically lyse Hu/Dd target cells infected with the HIV-1 prototypic isolates IIIB, MN, WMJ II, SF2, and CC as well as several HIV-1 clinical isolates. These results demonstrate that CTL determinants for HIV-1 env exist outside the hypervariable V3 region, anti-HIV-1 IIIB env CTL appear to recognize common determinants on diverse HIV-1 strains, and classification of HIV-1 strains based on neutralizing antibody reactivities does not appear to correspond to CTL recognition and lysis. The results suggest that the cell-mediated components of the immune system may have a broader recognition of divergent HIV-1 strains than do the humoral components. PMID- 8497059 TI - The vaccinia virus 14-kilodalton fusion protein forms a stable complex with the processed protein encoded by the vaccinia virus A17L gene. AB - The mechanism by which the 14-kDa fusion protein of vaccinia virus (VV) is anchored in the envelope of intracellular naked virions (INV) is not understood. In this investigation, we demonstrate that the 14-kDa protein interacts with another virus protein with an apparent molecular mass of 21 kDa. Microsequence analysis of the N terminus of the 21-kDa protein revealed that this protein is encoded by the VV A17L gene. The 21-kDa protein is processed from a 23-kDa precursor, by cleavage at amino acid position 16, at the consensus motif Ala-Gly Ala, previously identified as a cleavage site for several VV structural proteins. The 21-kDa protein contains two large internal hydrophobic domains characteristic of membrane proteins. Pulse-chase analysis showed that within 1 h after synthesis, the 14-kDa protein forms a stable complex with the 21-kDa protein. Formation of the complex was not inhibited by rifampin, indicating that the interaction between these two proteins occurs prior to virion morphogenesis. Immunoprecipitation analysis of disrupted virions showed the presence of the 21 kDa protein in the viral particle. Release of the 14-kDa-21-kDa protein complex from INV required treatment with the nonionic detergent Nonidet P-40 and a reducing agent. The protein complex consisted of 14-kDa trimers and of 21-kDa dimers. Since the 14-kDa fusion protein lacks a signal sequence and a large hydrophobic domain characteristic of membrane proteins, our findings suggest that the 21-kDa protein serves to anchor the 14-kDa protein to the envelope of INV. PMID- 8497060 TI - Juxtaposition between activation and basic domains of human immunodeficiency virus type 1 Tat is required for optimal interactions between Tat and TAR. AB - trans activation of the human immunodeficiency virus type 1 long terminal repeat requires that the viral trans activator Tat interact with the trans-acting responsive region (TAR) RNA. Although the N-terminal 47 amino acids represent an independent activation domain that functions via heterologous nucleic acid binding proteins, sequences of Tat that are required for interactions between Tat and TAR in cells have not been defined. Although in vitro binding studies suggested that the nine basic amino acids from positions 48 to 57 in Tat bind efficiently to the 5' bulge in the TAR RNA stem-loop, by creating several mutants of Tat and new hybrid proteins between Tat and the coat protein of bacteriophage R17, we determined that this arginine-rich domain is not sufficient for interactions between Tat and TAR in vivo. Rather, the activation domain is also required and must be juxtaposed to the basic domain. Thus, in vitro TAR RNA binding does not translate to function in vivo, which suggests that other proteins are important for specific and productive interactions between Tat and TAR. PMID- 8497061 TI - Hepatitis B virus differentially suppresses myelopoiesis and displays tropism for immature hematopoietic cells. AB - The hematopoietic cell lines HL-60 and THP-1 were challenged with hepatitis B virus (HBV) in vitro to study interactions between the virus and host cell. Exposure to HBV suppressed the ability of HL-60 cells to differentiate into granulocytes after treatment with retinoic acid (RA) or dimethyl sulfoxide (DMSO), and RA-induced activation of the monocytic cell line THP-1 was also suppressed. Terminal differentiation of both cell lines by phorbol 12-myristate 13-acetate (PMA) was not affected by HBV. The suppressive effect on RA- or DMSO induced differentiation was unique to HBV, since cell exposure to human cytomegalovirus, another virus that inhibits hematopoiesis, failed to block cellular differentiation. At 5 days postinfection, extracellular viral DNA was detected in immature but not in differentiated cultures and higher levels of core antigen (HBcAg) and surface antigen (HBsAg) were seen in undifferentiated cells than in RA- or PMA-treated cells. In addition, release of HBsAg into the medium was 2 to 12 times greater in untreated cultures than for RA- or PMA-treated cells. Thus, HBV suppresses hematopoiesis by blocking the maturational development of progenitors and selectively infects immature myeloid cells compared with mature end-stage cells. PMID- 8497062 TI - Identification and characterization of lef-1, a baculovirus gene involved in late and very late gene expression. AB - An Autographa californica nuclear polyhedrosis virus (AcMNPV) gene required in transient expression assays for late and very late viral gene expression was identified, sequenced, and transcriptionally mapped. This gene, designated late expression factor 1 (lef-1), was located between 7.4 and 8.7 map units of the AcMNPV physical map. It was identified by cotransfecting Spodoptera frugiperda cultured cells with a collection of overlapping cloned DNA fragments covering the entire AcMNPV genome and a reporter gene controlled by an early, late, or very late AcMNPV promoter. Omission of the DNA fragment containing lef-1 curtailed most late and very late gene expression but not early gene expression. lef-1 was found to be an early gene transcribed as a 1.8-kb RNA in the presence of the protein synthesis inhibitor cycloheximide. The C terminus of the predicted polypeptide product, LEF-1, contained a sequence motif characteristic of nucleoside triphosphate-binding sites. PMID- 8497063 TI - cis-acting requirements for the replication of flock house virus RNA 2. AB - To examine the cis-acting requirements for RNA replication, a cDNA clone of flock house virus (FHV) RNA 2 was transfected into baby hamster kidney cells and transcribed to yield RNAs that had terminal extensions of different lengths or that lacked internal regions of the molecule. These RNAs were tested for their ability to be replicated by FHV replicase that was provided by cotransfection of purified FHV RNA 1. The results showed that RNA replication was inhibited by terminal extensions, particularly those at the 5' end of the RNA, despite the fact that these extensions were corrected during RNA replication. A negative sense transcript with a 12-nucleotide 3' extension was replicated to produce a positive-sense RNA that had the correct 5' end, showing that the replicase could select its correct initiation site from within a longer template. A uridine residue at the second position of the positive strand was an important determinant of template activity. RNA molecules with large internal deletions that amounted to almost 50% of the 1,400 nucleotides of RNA 2 replicated as efficiently as full-length molecules, but only if they contained an internal region that lay between nucleotides 538 and 616. Thirty-six spontaneous deletions of RNA 2 that arose during sequential replicative passages all conserved the same internal region of the molecule. These results establish that both terminal and internal regions of FHV RNA 2 play essential roles in making the molecule a competent template for replication. PMID- 8497064 TI - Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study. AB - The secondary structure of the precursor (gp160) of the envelope protein of human immunodeficiency virus type 1 (BH10) and its receptor-binding subunit (gp120) was studied by Fourier-transformed attenuated total reflection spectroscopy. A higher alpha-helix/beta-sheet ratio in the gp120 subunit than in the precursor indicates a structural heterogeneity between the two subunits (gp120 and gp41), in agreement with classical secondary-structure predictions. The secondary structure of gp41 was estimated and compared with existing models. The high alpha-helical content in gp41 and the dominant beta-sheet content in gp120 resemble the distribution in influenza virus hemagglutinin subunits. PMID- 8497065 TI - Genetic heterogeneity among isolates of Ross River virus from different geographical regions. AB - The RNase T1 maps of 80 isolates of Ross River virus from different regions of mainland Australia and the Pacific Islands were compared. Four different clusters of isolates with greater than an estimated 5 to 6% diversity at the nucleotide level were found. There was a pattern of differences between eastern and western Australian strains; however, the pattern was disturbed by overlaps and incursants. Pacific Islands isolates belonged to the eastern Australian topotype. Our findings suggest that certain genetic types of Ross River virus predominate in different geographical regions. In contrast, populations of other important Australian arboviruses (Murray Valley encephalitis, Kunjin, and Sindbis viruses) are distributed across the Australian continent as minor variants of one strain. Our data also show that in one region, strains of Ross River virus with identical RNase T1 maps circulate during both years when epidemics occur and years when they do not. This finding suggests that Ross River virus epidemics are not dependent on the introduction or evolution of new strains of the virus. Two strains, belonging to the eastern Australian topotype, were isolated in Western Australia. It is likely that viremic humans or possibly domestic livestock travelling by aircraft were responsible for this movement. PMID- 8497066 TI - RNA-binding properties of a translational activator, the adenovirus L4 100 kilodalton protein. AB - The adenovirus L4 100-kDa nonstructural protein (100K protein) is required for efficient initiation of translation of viral late mRNA species during the late mRNA species during the late phase of infection (B. W. Hayes, G. C. Telling, M. M. Myat, J. F. Williams, and S. J. Flint, J. Virol. 64:2732-2742, 1990). The RNA binding properties of this protein were analyzed in an immunoprecipitation assay with the 100K-specific monoclonal antibody 2100K-1 (C. L. Cepko and P. A. Sharp, Virology 129:137-154, 1983). Coprecipitation of the 100K protein and 3H-infected cell RNA was demonstrated. The RNA-binding activity of the 100K protein was inhibited by single-stranded DNA but not by double-stranded DNA, double-stranded RNA, or tRNA. Competition assays were used to investigate the specificity with which the 100K protein binds to RNA in vitro. Although the protein exhibited a strong preference for the ribohomopolymer poly(U) or poly(G), no specific binding to viral mRNA species could be detected; uninfected or adenovirus type 5-infected HeLa cell poly(A)-containing and poly(A)-lacking RNAs were all effective inhibitors of binding of the protein to viral late mRNA. Similar results were obtained when the binding of the 100K protein to a single, in vitro-synthesized L2 mRNA was assessed. The poly(U)-binding activity of the 100K protein was used to compare the RNA-binding properties of the 100K protein prepared from cells infected by adenovirus type 5 and the H5ts1 mutant (B. W. Hayes, G. C. Telling, M. M. Myat, J. F. Williams, and S. J. Flint, J. Virol. 64:2732-2742, 1990). A temperature-dependent decrease in H5ts1 100K protein binding was observed, correlating with the impaired translational function of this protein in vivo. By contrast, wild-type 100K protein RNA binding was unaffected by temperature. These data suggest that the 100K protein acts to increase the translational efficiency of viral late mRNA species by a mechanism that involves binding to RNA. PMID- 8497067 TI - Legitimate and illegitimate cleavage of human immunodeficiency virus glycoproteins by furin. AB - Coexpression of human immunodeficiency virus type 1 glycoproteins with the subtilisin-like protease furin leads to processing of gp160 and gp140, a truncated form of gp160, to gp120. In addition, we show that gp120 itself is further cleaved by furin at sites near the primary cleavage site and within the V3 loop. PMID- 8497068 TI - Subgenomic RNA sequence of human astrovirus supports classification of Astroviridae as a new family of RNA viruses. AB - We report the sequence of the subgenomic RNA of human astrovirus serotype 2. This 2,484-nucleotide RNA contains a single open reading frame, which encodes a protein with a predicted molecular mass of 88 kDa. We propose that this protein is the 90-kDa capsid precursor observed in infected cells. The deduced protein sequence does not contain conserved amino acid patterns reported for the capsid proteins of picornaviruses or caliciviruses, consistent with the classification of astroviruses as a new family of RNA viruses, designated Astroviridae. PMID- 8497069 TI - Mutational analysis of the leucine zipper-like motif of the human immunodeficiency virus type 1 envelope transmembrane glycoprotein. AB - The N-terminal region of the envelope (env) transmembrane protein of human immunodeficiency virus type 1 (HIV-1) has a leucine zipper-like motif. This highly conserved zipper motif, which consists of a heptad repeat of leucine or isoleucine residues, has been suggested to play a role in HIV-1 env glycoprotein oligomerization. This hypothesis was tested by replacing the highly conserved leucine or isoleucine residues in the zipper motif with a strong alpha-helix breaker, proline. We report here that such substitutions did not abolish the ability of env protein to form oligomers, indicating that this highly conserved zipper motif does not have a crucial role in env protein oligomerization. However, the mutant viruses all showed impaired infectivity, suggesting that this conserved zipper motif can have an important role in the virus life cycle. PMID- 8497070 TI - Effect of linker insertion mutations in the human immunodeficiency virus type 1 gag gene on activation of viral protease expressed in bacteria. AB - We have expressed the human immunodeficiency virus type 1 (HIV-1) protease (PR) in bacteria as a Gag-PR polyprotein (J. Luban and S.P. Goff, J. Virol. 65:3203 3212, 1991). The protein displays enzymatic activity, cleaving the Gag polyprotein precursor Pr55gag to the expected products. The PR enzyme is only active as a dimer, and we hypothesized that PR activation might be used as an indicator of polyprotein multimerization. We constructed 25 linker insertion mutations throughout gag and assessed the PR activity of mutant Gag-PR polyproteins by the appearance of Gag cleavage products in bacterial lysates. All mutant constructs produced stable protein in bacteria. PR activity of the majority of the Gag-PR mutants was indistinguishable from that of the wild type. Six mutants, one with an insertion in the matrix (MA), four with insertions in the capsid (CA), and one with insertions in the nucleocapsid (NC), globally disrupted polyprotein processing. When PR was provided in trans on a separate plasmid, the Gag proteins were cleaved with wild-type efficiency. These results suggest that the gag mutations identified as disruptive of polyprotein processing did not conceal the scissile bonds of the polyprotein. Rather, the mutations prevented PR activation in the context of a Gag-PR polyprotein, perhaps by preventing polyprotein dimerization. PMID- 8497071 TI - Transforming variants of the avian myc-containing retrovirus FH3 arise prior to phenotypic selection. AB - The avian retrovirus FH3, which encodes a Gag-Myc fusion protein, transforms chicken macrophages but not fibroblasts. However, passage of FH3 viral stock in fibroblasts leads to emergence of a virus capable of fibroblast transformation. This virus has not acquired myc mutations; instead, it carries internal gag deletions which confer the ability to transform fibroblasts. We now demonstrate that this and similar deletion variants emerge repeatedly during selection. Sequence analysis reveals direct repeats at or near deletion junctions, suggesting that errors during reverse transcription may be involved in genesis of these viruses, which are then positively selected in fibroblast culture. By using the polymerase chain reaction, we found that such variants preexisted in original stocks even before selection, although they could not be detected by focus assay. PMID- 8497072 TI - Association of human immunodeficiency virus type 1 envelope glycoprotein with particles depends on interactions between the third variable and conserved regions of gp120. AB - Many regions within the envelope of human immunodeficiency virus type 1 (HIV-1) that affect its structure and function have been identified. We have previously reported that the interaction of the second conserved (C2) and third variable (V3) regions of gp120 influences the ability of HIV-1 to establish a productive infection in susceptible cells. To better understand the basis for this interaction, we have conducted structure-function analyses of envelope expressed from molecular proviral clones of HIV-1 containing defined mutations in C2 and V3 that individually and in combination differentially affect envelope function. The substitution of a glutamine for an asparagine residue (Q-267) at a potential asparagine-linked glycosylation site in C2, which severely impairs virus infectivity, reduces intracellular processing of gp160 into gp120, the association of gp120 with virions, and the ability of gp120 to bind to the HIV-1 cell surface receptor protein, CD4. The change of an arginine to an isoleucine codon in V3 (I-308), in the presence of the Q-267 mutation, restores virus infectivity to near wild-type levels by increasing the amount of gp120 associated with virions as compared with the Q-267 mutant but does not compensate for the Q 267-induced processing defect. The I-308 change in the context of the wild-type HIV-1 has no affect on processing, association, or CD4 binding. These results indicate that the impaired infectivity of the Q-267 mutant virus is due to a marked reduction in the amount of virion gp120 and suggest that the interaction of C2 and V3 stabilizes the association of gp120 with gp41. PMID- 8497073 TI - A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. AB - Specific point mutations which affect viral tropism have been identified in both the V3 loop and in the CD4-binding region of the human immunodeficiency virus type 1 surface glycoprotein gp120. Here we report that a single point mutation in the first variable region (V1) of human immunodeficiency virus type 1 strain JRCSF is responsible for a change in viral tropism. PMID- 8497074 TI - A monoclonal antibody to the CDR-3 region of CD4 inhibits soluble CD4 binding to virions of human immunodeficiency virus type 1. AB - The CDR-3 region of CD4 has been proposed to be involved in the fusion reaction between human immunodeficiency virus type 1 (HIV-1) and CD4+ cells, either at a stage involving virus binding or subsequent to virus binding. Part of the evidence for this has been the observation that monoclonal antibodies (MAbs) to CDR-3 block HIV infection potently without strongly inhibiting the binding of monomeric gp120 to CD4. Here I show that, in a system using oligomeric, virion bound gp120, a MAb to CDR-3 resembles those to CDR-2 in that it inhibits soluble CD4 binding to virions. Consequently, ternary complexes of MAb-soluble CD4-gp120 cannot be detected with CDR-2 MAbs and are detectable only at a very low level with a CDR-3 MAb, but they clearly form when a control MAb to CD4 domain 4 is used. Although not in direct conflict with previously published data on the role of CDR-3 MAbs in the inhibition of HIV-1 infection, these experiments do not support the hypothesis that the CDR-3 region is specifically involved in virus entry at a postbinding stage. PMID- 8497075 TI - The cowpea mosaic virus M RNA-encoded 48-kilodalton protein is responsible for induction of tubular structures in protoplasts. AB - Tubular structures extending from plasmodesmata in cowpea mosaic virus (CPMV) infected tissue have been implicated to play an important role in cell-to-cell movement of this virus. Using a cauliflower mosaic virus 35S promoter-based transient expression vector, we show that expression of only the CPMV M RNA encoded 48-kDa protein (48K protein) in cowpea protoplasts is sufficient to induce these structures. Strikingly, expression of the 48K protein in protoplasts from a number of nonhost plant species, such as barley, Arabidopsis thaliana, and carrot, also resulted in tubular structure formation. Thus, it is not likely that the viral 48K protein, though playing a key role in cell-to-cell movement of CPMV, has a role in determining the host range of CPMV. PMID- 8497076 TI - Increased hematopoiesis in mice soon after infection by Friend murine leukemia virus. AB - Friend murine leukemia virus (F-MuLV), an erythroleukemogenic replication competent retrovirus, induces leukemia in its host after a long latency. However, the early effects of infection may determine the pathway that eventually leads to malignant transformation. To determine how F-MuLV affects host cell proliferation soon after infection, BALB/c mice were inoculated with virus and then were assayed for susceptibility to appropriately pseudotyped spleen focus-forming virus (SFFV) as an indicator of erythropoietic activity. Twelve-week-old mice exposed to F-MuLV for 9 days were more susceptible (by a factor of 30) to superinfection by SFFV than were nonviremic mice. To test whether increased susceptibility was the result of increased hematopoietic activity, hematopoietic progenitors from the spleens of F-MuLV-infected mice were enumerated with a clonal culture assay. Nine days after inoculation with F-MuLV, the numbers of colony-forming progenitors increased by a factor of 4. Morphological analysis of the cultured colonies showed that erythroid, granulocytic, monocytic, and mixed granulocytic-monocytic progenitors all had increased. Thus, F-MuLV more rapidly induced a generalized increase in hematopoiesis than has previously been reported. The splenic hyperplasia induced by F-MuLV soon after infection may explain its ability to accelerate leukemogenesis in mice also infected by the polytropic Friend mink cell focus-forming virus. PMID- 8497077 TI - Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody. AB - The contributions of the first and second variable regions of the human immunodeficiency virus type 1 gp120 glycoprotein to envelope glycoprotein structure, function, and recognition by a neutralizing antibody were studied. Several mutants with substitutions in the V2 loop demonstrated complete dissociation of the gp120 and gp41 glycoproteins, suggesting that inappropriate changes in V2 conformation can affect subunit assembly. Some glycoproteins with changes in V1 or V2 were efficiently expressed on the cell surface and were able to bind CD4 but were deficient in syncytium formation and/or virus entry. Recognition of gp120 by the neutralizing monoclonal antibody G3-4 was affected by particular substitutions affecting residues 176 to 184 in the V2 loop. These results suggest that the V1/V2 variable regions of the human immunodeficiency virus type 1 gp120 glycoprotein play a role in postreceptor binding events in the membrane fusion process and can act as a target for neutralizing antibodies. PMID- 8497078 TI - Insurance associated with AIDS mortality rates. PMID- 8497079 TI - Extraordinary epidemiologic, environmental health experience emerges from operation Restore Hope. PMID- 8497080 TI - New research center added to fight against AIDS. PMID- 8497081 TI - From the Surgeon General, US Public Health Service. PMID- 8497082 TI - From the Centers for Disease Control and Prevention. Measles--United States, 1992. PMID- 8497083 TI - From the Centers for Disease Control and Prevention. Years of potential life lost before age 65--United States, 1990 and 1991. PMID- 8497084 TI - Crack cocaine use and sexual behavior among people with AIDS. PMID- 8497085 TI - False-positive HIV test: implications for the patient. PMID- 8497086 TI - Terminal illness and risk of suicide. PMID- 8497087 TI - AIDS: reason for optimism? PMID- 8497088 TI - Tacrine in Alzheimer's disease. PMID- 8497089 TI - Detection of HIV DNA in cervical and vaginal secretions. Prevalence and correlates among women in Nairobi, Kenya. AB - OBJECTIVE: Factors that influence heterosexual transmission of the human immunodeficiency virus (HIV), including sexually transmitted diseases, contraceptive practices, sexual practices, HIV-related immunosuppression, and presence of cervical ectopy and the penile foreskin, have been identified through cross-sectional and prospective cohort epidemiological studies. To more directly characterize factors that influence infectivity, we conducted a study of HIV shedding from the genital tract in women. DESIGN: Ninety-seven HIV-seropositive women attending a sexually transmitted disease clinic in Nairobi, Kenya, completed a questionnaire and underwent a physical examination and an evaluation for sexually transmitted diseases. Cervical and vaginal secretions were obtained for HIV DNA detection using polymerase chain reaction amplification. RESULTS: Human immunodeficiency virus DNA was detected by polymerase chain reaction in 28 (33%) of 84 cervical samples and 13 (17%) of 77 vaginal samples. The prevalence of HIV was higher in specimens from the endocervix than from the vaginal wall (P = .002), and there was no correlation between presence of virus at the two sites. After adjusting for age, cervical HIV shedding was independently associated with oral contraceptive pill use (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.7 to 77.6), cervical mucopus (OR, 6.2; 95% CI, 0.9 to 41.4; P = .05), cervical ectopy (OR, 5.0; 95% CI, 1.5 to 16.9), and pregnancy (OR, 4.5; 95% CI, 1.2 to 16.3). CONCLUSIONS: Human immunodeficiency virus was detected in one third of cervical samples and one sixth of vaginal samples. The presence of HIV DNA in cervical secretions was significantly associated with oral contraceptive pill use, cervical ectopy, and pregnancy. There was a marginally significant association with cervical mucopus. The identification of factors that increase the infectivity of women suggests potential strategies for reducing heterosexual transmission of HIV. PMID- 8497090 TI - Trends in death with tuberculosis during the AIDS era. AB - OBJECTIVE: To describe and analyze recent changes in tuberculosis mortality in the United States during the acquired immunodeficiency syndrome (AIDS) epidemic. DESIGN: We used National Center for Health Statistics multiple-cause mortality data and analyzed deaths with tuberculosis (1980 through 1990) and/or AIDS (1987 through 1990) as an underlying or associated cause. We also categorized the 50 states and the District of Columbia into high (five states), medium (23 states), and low (23 states) AIDS incidence groups and then compared the groups' rates of death with tuberculosis during the period 1980 through 1990. STUDY POPULATION: Residents of the United States who died in the period 1980 through 1990. MAIN OUTCOME MEASURES: Death certificates indicating AIDS and/or tuberculosis. RESULTS: A bimodal age distribution of persons dying with tuberculosis has emerged concurrent with the AIDS epidemic. A new peak spanning the ages 20 to 49 years accompanies the preexisting peak in the elderly. In 1990, 54.2% (729/1344) of the deaths with tuberculosis in persons 20 to 49 years of age occurred in persons who also had AIDS listed on their death certificates. During the period 1987 through 1990, there was an increasing trend in the proportion of AIDS deaths that also had tuberculosis: 2.3% (353/15,075) in 1987, 2.5% (460/18,649) in 1988, 3.0% (738/24,607) in 1989, and 3.0% (836/27,975) in 1990 (P < .001). Of AIDS deaths in 1990, 1.6% (253/15,565) of whites died with tuberculosis, compared with 4.7% (400/8533) of blacks (P < .001) and 4.7% (172/3666) of Hispanics (P < .001). In the high AIDS incidence states, the rate of death with tuberculosis in persons aged 20 to 49 years rose from 0.61 to 2.82 per 100,000 population in the period 1982 through 1990, an increase of 362%. For this age group in the states with medium and low AIDS incidence, the rates of death with tuberculosis during this period rose 52% and 47% (from 0.44 to 0.67 and from 0.19 to 0.28 per 100,000 population), respectively. The increases in the rate of death with tuberculosis within all three groups and the differences among the groups were all highly statistically significant (P < .001). CONCLUSION: The AIDS epidemic has significantly increased the number and rate of tuberculosis deaths in younger adults through 1990, although in this study discrimination of deaths due to tuberculosis from deaths with tuberculosis was not possible. Vigorous efforts to prevent and treat tuberculosis and AIDS are indicated to reverse the trends we have described. PMID- 8497091 TI - Absence of true seroreversion of HIV-1 antibody in seroreactive individuals. AB - OBJECTIVES: First, to determine whether there is evidence for loss of human immunodeficiency virus type 1 (HIV-1) antibody in seroreactive individuals. Second, if true seroreversion occurs, to determine its incidence relative to errors in the testing process. DESIGN: A retrospective cohort study reviewing the results of 5,446,161 HIV-1 antibody tests performed on 2,580,974 individuals (the US Army HIV Data System) from 1985 through 1992. For all patients with one or more seroreactive sample followed by one or more nonreactive sample, we examined available records and retested the samples. PARTICIPANTS: Serum samples had been obtained from active-duty and retired military personnel, their dependents, and applicants to the military. RESULTS: Of 4911 individuals reported to be seroreactive for HIV-1 by two independent samples, only six were potential seroreverters. Review of the six cases revealed that five actually were HIV seroreactive patients who had samples from nonreactive individuals mistakenly attributed to them, while the sixth had a testing error proven by retesting the discrepant specimen. Errors in the testing process were identified (n = 23) or suspected (n = 3) in another 26 individuals who had not had independent confirmation of reactivity by a second sample. The cumulative error rate was 12.4 per 1 million patients tested. An additional group of 31 uninfected infants appeared to serorevert due to loss of antibody acquired from their HIV-1-infected mothers. CONCLUSIONS: Review of this database demonstrates no evidence for true seroreversion of HIV-1 antibody status. We conclude that if seroreversion occurs at all, it is exceedingly rare. In fact, most (if not all) cases of apparent seroreversion represent errors of attribution or testing. PMID- 8497092 TI - Molecular targets of gene transfer therapy for HIV infection. PMID- 8497093 TI - Trends in HIV prevalence among disadvantaged youth. Survey results from a national job training program, 1988 through 1992. AB - OBJECTIVE: To describe trends in the prevalence of human immunodeficiency virus (HIV) among socially and educationally disadvantaged US youth. DESIGN: Analysis of demographic and geographic trends of HIV infection among Job Corps students from January 1988 through December 1992. SETTING: The Job Corps is a national training program for disadvantaged and out-of-school youth. POPULATION SCREENED: Youths aged 16 to 21 years who entered the Job Corps residential training centers during the survey period. MAIN OUTCOME MEASURE: Trends in prevalence of HIV infection among Job Corps students stratified by sex, age, race, and region of the country. RESULTS: Of the 269,956 Job Corps students screened, 812 (0.3%) tested positive for the antibody to HIV type 1. Seroprevalence of HIV for young men decreased from 3.6 per 1000 in 1988 to 2.2 per 1000 in 1992 (chi 2 test for trend, P < .001). Seroprevalence for young women increased from 2.1 per 1000 in 1988 to 4.2 per 1000 in 1990 (P = .001), with seroprevalence remaining stable from 1990 through 1992. The decreasing trends in HIV prevalence among men and increasing trends among women were primarily due to changes in seroprevalence in African-American students. CONCLUSIONS: The overall prevalence of HIV infection of three per 1000 is high, given the youth of Job Corps students. The significant rise in HIV rates among female Job Corps students provides evidence of the increasing risk of infection for socioeconomically disadvantaged young women. Reasons for the declining trend in HIV prevalence among male Job Corps students are not clear. Efforts to prevent the spread of HIV infection among adolescents must focus on the group that is hardest to reach--out-of-school and impoverished youth. PMID- 8497094 TI - Opiate dependency among the subscribers of a New York area private insurance plan. AB - OBJECTIVE: To estimate the prevalence of opiate use among the subscribers of a large private insurance plan, Empire Blue Cross and Blue Shield (EBCBS). DESIGN: Six and a half million hospital inpatient claims for the period January 1, 1982, through June 30, 1992, were reviewed. Thirty-one thousand eight hundred ten different individuals who had a total of 55,143 hospital admissions with a primary diagnosis of opiate dependency (International Classification of Diseases, Ninth Revision, Clinical Modification 304.0 and 304.7) were identified. In the same period, 17,493 EBCBS subscribers (15,191 male and 2302 female) were identified from hospital admissions data as having acquired immunodeficiency syndrome. These data were cross-matched with the opiate dependency data to estimate the "capture" of opiate users in the EBCBS subscribers with acquired immunodeficiency syndrome and to model the size of the opiate using population in EBCBS. RESULTS: It is estimated that between 1982 and 1992 EBCBS insured approximately 141,000 opiate users, 85,000 of whom are currently insured by EBCBS. CONCLUSION: There is a large population of insured opiate users who may be excluded from the estimates of the overall number of opiate users as insured opiate users are less likely to be counted via contact with government agencies. This suggests that current estimates of the number of opiate users and their social characteristics should be reconsidered. PMID- 8497095 TI - What can we expect from the 1993 International Conference on AIDS? PMID- 8497096 TI - The US race to 'cure' AIDS--at '4' on a scale of 10, says Dr Fauci. PMID- 8497097 TI - A piece of my mind. My heroes. PMID- 8497098 TI - Renal stones. PMID- 8497099 TI - Transcutaneous bilirubinometry: clinical application. AB - Simultaneous estimations of serum and transcutaneous bilirubin were done in 105 healthy, full term, jaundiced newborns. A good correlation was found between the transcutaneous and serum bilirubin values with coefficient of correlation 0.774. The observed sensitivity was 90%, specificity 78% and positive predictive value 64% at mean serum bilirubin concentration of 9.92 mg/dl. Two action levels at transcutaneous bilirubin values 15 and 18 were also generated that correlated with low and high serum bilirubin values; they can therefore be used for screening of jaundiced full term babies. This study indicates that the transcutaneous bilirubin meter is useful for screening of jaundiced neonates. PMID- 8497100 TI - Evaluation of the role of craniotomy in developing countries. AB - A review of 32 cases of craniotomy performed at the Jinnah Postgraduate Medical Centre Karachi, over a period of 6 years from January, 1984 to December, 1989 is presented. Total number of deliveries during this period were 37,682. Frequency of craniotomy was 0.08% i.e., 1 in 1177 deliveries. Of these 32 craniotomies, 28 were done on non-deformed dead fetus, 16 because of obstructed labour, 7 in cases of after coming head of breech and 5 in failure to progress in second stage of labour. Four cases were of live hydrocephalic fetus in whom cephalocentesis was done followed by craniotomy due to failure to progress in labour. Maternal morbidity was 12.5% with no maternal death. We conclude that it is safe and quicker than caesarean section in selected cases. Though unpleasant to perform, is of great relief to the patient and her family. PMID- 8497101 TI - Characterization of Reed-Sternberg cells with granulocyte specific monoclonal antibody. AB - Monoclonal antibody Leu M1 represents a highly specific marker to locate granulocyte antigen in Reed-Sternberg cells in Hodgkin's disease. Except the L&H variants of reed-sternberg cells in lymphocyte predominance variety in which antigens are probably sialylated. All the cases of non-Hodgkin's lymphoma were negative with this marker, because of absence of antigen. Therefore this specific marker characterizes granulocyte origin of reed-sternberg cells. PMID- 8497102 TI - Haematocrit values in ischaemic heart disease. AB - Haemoglobin (g/dl) and haematocrit (%) values were determined in 30 healthy controls and 40 patients with ischaemic heart disease. Both groups were non smokers. Haemoglobin and haematocrit values (mean +/- SE) in patients were 15.65 +/- 0.18 and 46.45 +/- 0.49 and in controls 14.30 +/- 0.14 and 41.50 +/- 0.23. Significantly higher (P < 0.001) haematocrit value by influencing the blood viscosity may impose extra burden on the ischaemic heart. PMID- 8497103 TI - Sotos syndrome; an endocrine and neurological maze. PMID- 8497104 TI - Lymphoma complicating ulcerative colitis. PMID- 8497105 TI - Fatal haematemesis due to impacted foreign body in the oesophagus. PMID- 8497106 TI - Does hypertension or aging modulate directional shortening of the left ventricular midwall? AB - It is unclear whether aging or hypertension modulates directional contractile function of the left ventricular (LV) wall. We investigated LV midwall shortening and thickening in 35 normal subjects and in 15 patients with mild-to-moderate systemic hypertension (HT) using 2-dimensional echocardiography. The normal subjects were divided into 3 subgroups according to age: 13 subjects below 30 years, 12 subjects over 31 and below 59 years, and 10 subjects over 60 years. In normal subjects of all ages, no significant difference was observed between meridional shortening (%Lm = 16.3 +/- 2.4) and circumferential shortening (%Lc = 17.1 +/- 4.0), and a significant increase in the short-axis cross-sectional area (CSA) of the LV wall at end-systole was observed (p < 0.001). No significant differences with age were found in the measurements, except that %Lc/%Lm was reduced (p < 0.05) in the elderly subgroup. In HT, all measured parameters, i.e., %Lm, %Lc, %Lc/%Lm, wall thickening, and the change in CSA, showed no difference from those of normal subjects. We conclude that the shortening of the normal LV midwall is similar in both meridional and circumferential directions, and that aging and mild-to-moderate HT do not significantly affect this characteristic, when echocardiographic measurements are taken at rest at end-diastole and end systole. This observation may be applied to simulation analyses of basic LV mechanics, such as the finite element method. PMID- 8497107 TI - Relationships between left ventricular mass, left ventricular work and coronary artery size in aortic regurgitation--possible mechanism of myocardial ischemia. AB - To investigate the relationships between coronary artery size, left ventricular (LV) mass, and LV stroke work in aortic regurgitation (AR), these values were measured in 19 patients with severe AR. Twenty normal subjects and 15 patients with mitral regurgitation (MR) were used as control groups. The coronary area index, i.e., the coronary cross-sectional area divided by body surface area (BSA), was larger in the AR group than in the control groups in all measured sites except for the peripheral left anterior descending coronary artery (LAD) and right coronary artery (RCA). However, the coronary area index divided by the LV mass was significantly smaller in AR and MR patients than in normal subjects. Furthermore, the coronary area index divided by LV stroke work was smaller in AR patients than in MR patients and normal subjects. These results suggest that the coronary blood flow associated with the increased LV mass and stroke work caused by regurgitation was insufficient in patients with severe AR, especially in the area of the LAD. Therefore, the occurrence of myocardial ischemia in patients with severe AR may involve inadequate enlargement of the coronary artery which perfuses the LV, in addition to factors such as decreased coronary perfusion pressure, increased coronary artery resistance and decreased coronary flow reserve. PMID- 8497108 TI - Effects of exercise and pacing loads on myocardial amino acid balance in patients with normal and stenotic coronary arteries, with special reference to branched chain amino acids. AB - Arterial and coronary sinus differences (A-S) of alanine, glutamate, isoleucine, leucine, valine and phenylalanine were measured in 7 control subjects and 12 patients with coronary artery disease (CAD) at rest and during exercise, and in 8 controls and 21 CAD patients at rest and during pacing. Lactate, great cardiac vein flow and oxygen were also measured. However, none of these parameters distinguished CAD from controls. Changes in alanine and glutamate during each load were, for the most part, consistent with previous studies, i.e., a greater release of alanine and uptake of glutamate was observed in the ischemic group. A S of isoleucine, leucine and valine showed significant positive correlation to that of alanine (r = 0.59, r = 0.89, r = 0.77, respectively, during exercise, and r = 0.57, r = 0.65, r = 0.72, respectively, during pacing). A-S of isoleucine, leucine and valine showed significant positive correlations to each arterial concentration during exercise (r = 0.54, r = 0.62, r = 0.63, respectively), but not during pacing. Although none of the uptakes of the branched chain amino acids (BCAA) were significant, the mean A-S of each BCAA was positive at rest in both controls and CAD, and declined during each load. A-S of leucine was significantly smaller in CAD than in controls during exercise (0.7 +/- 7.0 vs 6.8 +/- 4.1 mumol/l, p < 0.05) and those of leucine and valine were significantly smaller in CAD patients with ischemic electrocardiographic change than in those without electrocardiographic change during pacing (0.1 +/- 5.9 vs 6.1 +/- 5.5, p < 0.05; 3.1 +/- 10.1 vs 9.9 +/- 6.8 mumol/l, p < 0.01, respectively). These results suggest that BCAA, especially leucine and valine, tend to be taken up by human myocardium physiologically and show characteristic changes under myocardial stress similar to those seen with alanine and glutamate. PMID- 8497109 TI - Cerebral blood flow in asymptomatic individuals--relationship with cerebrovascular risk factors and magnetic resonance imaging signal abnormalities. AB - We studied the relationship between cortical grey matter flow (CBF) and age, cerebrovascular risk factors and the severity of subcortical hypersignals (HS, hyperintensity score in MRI) in 47 asymptomatic subjects with cerebrovascular risk factors. Multiple regression analysis revealed that HS was most strongly related to CBF, and that hematocrit, age and evidence of ischemic change detected in the electrocardiogram also appeared to be independent determinants of CBF. Both the severity and location of hypersignals were correlated with CBF. The most significant negative correlation observed was that between CBF and HS in the basal ganglia-thalamic region, where the degree of signal abnormality was modest. Decreased CBF in asymptomatic subjects with cerebrovascular risk factors may be related to (1) microcirculatory disturbance associated with elevated hematocrit and an increase in the number of risk factors, and (2) functional suppression of cerebral cortex due to the neuronal disconnection associated with subcortical lesions. In addition, impaired cerebral circulation may be related to MRI signal abnormalities. PMID- 8497110 TI - Alteration of pulmonary blood flow distribution in patients with congenital left to right cardiac shunt--pre- and postoperative study with macroaggregates of 99mTc-labeled human serum albumin. AB - The pulmonary blood flow in 84 patients with left to right cardiac shunts was preoperatively and postoperatively examined by scintigram with macroaggregates of 99mTc-labeled human serum albumin. Lung biopsy was also performed in 28 patients. The regional pulmonary blood flow distribution curves obtained from perpendicular scintillation to the long axis of the right lung in the supine position were classified into 4 patterns (normal and types 1 to 3). The normal pattern displayed uniform distribution, however type 1 demonstrated a lack of upper corner in the curve. Type 2 showed 2 peaks (a lower peak in the upper and a higher peak in the lower part of the lung) with a dip between them. Finally only 1 peak in the lower part of the lung was manifest in type 3. The right Upper/Lower lung count ratio, R(U/L), expressed as the mean +/- standard deviation in each curve type was 0.82 +/- 0.12 (n = 23), 0.71 +/- 0.11 (n = 28), 0.6 +/- 0.08 (n = 17) and 0.58 +/- 0.18 (n = 16), respectively. The count ratios from the 3 abnormal types were statistically significant compared to the normal curve type (p < 0.01). In addition, the type 1 and 2 curves were significant compared to type 3 (p < 0.05-0.01). In patients under 3 years of age, lower R (U/L) count ratio expressed more severe pulmonary hypertension. Negative correlations were observed with the peak pulmonary/peak systemic pressure ratio, Pp/Ps, (r = -0.66, p < 0.01) and with the pulmonary vascular resistance index, PVRI, (r = -0.45, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497111 TI - New interpretation of systolic time intervals from active cross-bridge model. AB - Using an active cross-bridge model proposed by the authors, it has been established theoretically that cross-bridge activation rate (Ka) of the left ventricular myocardium, which might correspond to the rate of binding of Ca2+ with troponin C, is approximately expressed as a simple formula: Ka = 3/electromechanical systole (sec-1), although no definitive biological proof has yet been provided for the equation. One hundred eighteen patients without significant cardiac disease and 6 patients who had atrioventricular block with a permanent pacemaker were evaluated to determine the Ka value of the normal human left ventricular myocardium (test 1), and to examine the effect of changes in heart rate (test 2) as well as afterloading (test 3) or dobutamine infusion (test 4) on Ka. The pacing rate was increased from 50 to 110 beats/min at 20-beat increments in test 2. Arterial pressure was elevated by angiotensin II infusion in test 3, and 7 subjects received a continuous dobutamine infusion in test 4. The Ka value was found to be related to heart rate, to be increased by dobutamine infusion, and to be decreased by myocardial lengthening due to afterloading. Dependence of Ka on heart rate appeared to result from changes in myocardial length. The Ka value corrected for heart rate (Kac) had an average variation of only 4.6%, and was unrelated to age or myocardial length in individual subjects. Thus, the Kac value of normal human left ventricular myocardium appears to be nearly constant between individuals but to be increased by catecholamine infusion or myocardial shortening. PMID- 8497112 TI - Age-related modification of regional left ventricular filling in normal subjects. AB - Left ventricular diastolic filling has been reported to be impaired with advancing age in normal subjects. To investigate the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age and to assess the location of asynchronous regions within the left ventricle, radionuclide ventriculography was conducted in 48 normal subjects aged 15 to 73 years. Left ventricular regional filling was assessed by dividing the left ventricular region of interest into 4 quadrants, from which global, septal, apical and lateral time-activity curves and first-derivative curves were derived. Indexes of global left ventricular systolic function at rest did not correlate with age. However, indexes of global early diastolic filling declined significantly with age; peak filling rate normalized to end-diastolic volume (r = -0.42; p < 0.01), to stroke volume (r = -0.48; p < 0.001) and to peak ejection rate (r = -0.47; p < 0.001) decreased with advancing age. Global time to peak filling rate also increased with aging (r = 0.41; p < 0.01). Early diastolic asynchrony was measured as the sum of the absolute values of the time differences from global peak filling rate to that in each of three quadrants (delta TPFR). delta TPFR increased with age (r = 0.37; p < 0.01). Global peak filling rate normalized to end-diastolic volume (r = -0.40; p < 0.01), to stroke volume (r = 0.45; p < 0.01) and to peak ejection rate (r = -0.51; p < 0.001) decreased significantly with increasing delta TPFR. Time to peak filling rate of the lateral region occurred first (163 +/- 33 ms), followed by the apical (184 +/- 38 ms) and finally the septal region (195 +/- 35 ms). With regard to the sequence of regional filling, this suggests that a physiologic asynchrony exists in resting condition in normal subjects. Times to peak filling rate in the septal and apical regions were modestly correlated with age (r = 0.29; p < 0.05, r = 0.30; p < 0.05 respectively), but that in the lateral region did not show significant correlation with age. This may indicated that the effects of advancing age on the regional filling differ in regions within the left ventricle. These results suggest that aging alters left ventricular early diastolic filling in association with the increase in physiologic asynchrony. PMID- 8497113 TI - Evaluation of intravascular hemolysis by haptoglobin administration after prosthetic valve replacement. AB - Although the measurement of serum haptoglobin (S-Hp) is of great use for evaluation of intravascular hemolysis, it is not applicable in patients with mechanical prosthetic valves because S-Hp is virtually absent. We administered haptoglobin preparation to 10 patients with Bjork-Shiley mitral prosthetic valves and 10 patients with the same aortic prosthetic valves. Serum haptoglobin levels were measured periodically afterwards. The maximum haptoglobin levels (Hp (max)), serum, haptoglobin reducing rate ((Hp-delta Hp)/delta t) and expected haptoglobin disappearing time (hours) were obtained from the subsequent samples. The screening studies which were performed at the same time were not predictors of difference in the 2 groups. On the other hand, serum haptoglobin reducing rate and expected haptoglobin disappearing time indicated that hemolysis is higher in patients with an aortic prosthetic valve than with a mitral prosthetic valve. This haptoglobin administration test seems to be useful for the comparative examination of the intravascular hemolysis caused by the difference in the position of the prosthetic valve. PMID- 8497114 TI - Are diabetic hearts more resistant to ischemia/reperfusion injury? AB - The present study was designed to investigate the cardiac impairment during ischemia/reperfusion injury in rats with streptozotocin-induced diabetes vs controls. Male rats were divided into three groups: controls, one-week diabetic rats (1wDM) and four-week diabetic rats (4wDM). In the isolated working heart, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum positive and negative dP/dt were measured before ischemia and after 20 min of global ischemia followed by 30 min reperfusion. In the pre-ischemic state, hearts of 4wDM showed a significant (p < 0.05) depression of the maximum positive and negative dP/dt compared with those of controls and 1wDM. There were no significant differences in LVDP and LVEDP among the three groups. The incidence of reperfusion-induced ventricular fibrillation (VF) was 75% for controls, 15% for 1wDM rats, and 27% for 4wDM rats. In hearts without reperfusion-induced VF, there were no differences in the three groups, between the pre- and post-ischemic values in LVDP, LVEDP, and maximum positive and negative dP/dt. These findings suggest that diabetic hearts exhibit no susceptibility to ischemia/reperfusion injury. PMID- 8497115 TI - Effects of phospholipase C on action potentials and intracellular Ca2+ concentration in guinea pig heart. AB - To clarify the role of phospholipase C (PLC) in arrythmias and cell injury during myocardial ischemia/reperfusion, we studied its effects on electrophysiology and [Ca2+]i in guinea pig hearts. After exposure to PLC (1 and 2 U/ml), the action potential durations of right ventricular papillary muscles were decreased. Delayed afterdepolarizations were observed in all of the preparations, and some developed into triggered activities. Developed tension decreased after an initial increase for the first 5 min, while resting tension increased consistently. The effects of PLC (0.02, 0.1, and 0.2 U/ml) on [Ca2+]i of ventricular myocytes were measured using fura-2 fluorescence. The ratio of rod-shaped cells to all cells decreased in a time- and a concentration-dependent manner. Perfusion with 0.1 U/ml PLC elevated [Ca2+]i from 56 +/- 5 nM to 245 +/- 47 nM before cell rounding, and to 1167 +/- 172 nM after cell rounding, suggesting that PLC causes Ca2+ overload. In conclusion, activation of PLC may play a role in arrhythmias and cell injury during ischemia/reperfusion. The increase in [Ca2+]i during ischemia/reperfusion may activate phospholipase, which would further increase [Ca2+]i to form a vicious cycle. PMID- 8497117 TI - [Abstracts of the 66th annual meeting of Japan Association of Industrial Health]. PMID- 8497116 TI - Closure of ventricular septal rupture caused by acute myocardial infarction using a transaortic balloon catheter. AB - We report a case of successful transaortic closure of a postinfarction ventricular septal rupture using a Swan-Ganz catheter. The method markedly reduced a left-to-right shunt and the improved hemodynamic condition of the patient, an 81-year-old woman, was maintained for about a week before surgical treatment. Inflation of the balloon with water made the balloon visible via echocardiography and was effective in maintaining inflation and echocardiographic follow-up. PMID- 8497118 TI - [Tuberculin sensitivity to purified protein derivatives (PPD) from M. intracellulare (PPD-B), M. kansasii (PPD-Y), M. fortuitum (PPD-Y) and M. tuberculosis (PPDs) among healthy volunteers]. AB - To reveal the epidemiology of mycobacteria other than Mycobacterium tuberculosis in Japan, we tested 379 healthy volunteers from Self Defence Force Army stationed in Hiroshima Prefecture with 0.05mcg of PPDs, 0.1mcg of PPD-B, PPD-Y and PPD-F. Majority of the volunteers had been immunized with BCG by thirteen years old. Rate of positive reaction (diameter of redness > or = 10mm) in each PPD in each age group were; PPDs [18-19yr (n = 39); 30.8%, 20-29yr (n = 178); 63.5%, 30-39yr (n = 78); 91.0%, 40-53yr (n = 84); 92.9%], PPD-B [12.8%, 24.7%, 38.5%, 48.8%], PPD-Y [5.1%, 14.6%, 26.9%, 26.2%], PPD-F [0%, 10.1%, 12.8%, 10.7%]. Frequency distribution curve of PPDs in age groups above 20 years old had a peak at about 14mm of diameter, while low-responder were dominant in age 18 to 19. In PPD-B, there were two peaks, one in less than 5mm and the other between 10 to 15mm which was considered as the group sensitized by M. avium complex and became larger in older age group. In PPD-Y and in PPD-F, the frequency distribution showed an exponential curve with a little shift to right in older group in PPD-Y. As there was a considerable degree of cross-sensitivity, we provisionally regarded the maximum reaction of four PPD (larger than 5mm) or the reaction which is 75 per cent or more of each person's maximum reaction as specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497119 TI - [In vitro antimycobacterial activity of clarithromycin and its therapeutic efficacy against Mycobacterium intracellulare infection induced in mice]. AB - A new macrolide, clarithromycin (CAM), with increased acid-stability and thus having a markedly improved absorption efficiency from gastrointestinal tract, was evaluated for its in vitro antimicrobial activity against various mycobacterial species. CAM had nearly the same level of anti-mycobacterial activity as that of sparfloxacin (SPFX) and slightly higher activity than rifampicin (RFP), except that its anti-M. tuberculosis activity was much lower than those of SPFX and RFP. Anti-M. avium complex activity of CAM (MIC90 values against M. avium and M. intracellulare were 12.5 and 6.25 micrograms/ml, respectively) was in similar level as SPFX and RFP. However, MIC distribution pattern revealed that anti-M. avium activity was in the order of SPFX > CAM > RFP, while anti-M. intracellulare activities of them were almost the same with each other. Moreover, CAM showed bactericidal action against M. intracellulare growing in 7H9 medium. Furthermore, we investigated the therapeutic efficacy of CAM against M. intracellulare infection induced in mice and also determined its combined effect with other antimicrobials including KRM-1648, SPFX and ethambutol (EB). When CAM suspended in 5% gum arabic-saline was given s.c. to mice infected i.v. with M. intracellulare (8 x 10(6) CFU) at 0.2 to 2 mg/mouse/day, once daily six times per week from day 1 for 8 weeks, CAM exhibited a potent therapeutic efficacy, in terms of reduction in the incidence of gross lung lesions and reduction of bacterial loads in the visceral organs (reduction of bacterial CFU by 0.9-3.4 log units in the lung and by 0.4-4.6 log units in the spleen during week 4 to 8, depending on its administration dose).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497120 TI - [A study of ambulatory treatment for pulmonary tuberculosis in foreigners residing in Japan]. AB - We studied 130 cases of pulmonary tuberculosis in foreigners residing in Japan to obtain the results as follows; 1. Of the cases of pulmonary tuberculosis in foreigners who are registered and receiving treatment in Japan, 20.3% were treated at three dispensaries of the Japan Antituberculosis Association in Tokyo. 2. The nationality of the cases treated was China in more than half of them, followed by the Republic of Korea. 3. The number of days taken from entry into Japan to the start of treatment was about 11.4 months; 0.9% of the total number of cases examined by chest radiophotography required medical treatment. 4. Their living conditions in Japan according to questionnairing are: 56.2% have jobs in Japan; working hour, 4.99 +/- 1.19 hours a day; 64.4% take night work; 57.6% work in food/drink service industry; living space is 12.5 m2; 52.4% share the same house with other persons, living together with 1.6 persons. 5. As for the type of illness at the start of treatment, GAKKAI classification type III accounted for 90% and spread 1 83.8%. GAKKAI classification type II accounted for 10%, consisting of many relatively mild cases. 6. The defaulter rate was high at 40.8%. The reason for defaulting was broken down to discontinuation on his own 68%, repatriation 15% and side-effects 19%. The time to default was average 3.2 +/- 3.1 months after the start of treatment. They defaulted 1.2 +/- 0.4 times on the average. 7. To reduce the defaulter rate to the minimum in treating the foreigners residing in Japan, the following may be needed. a. To give guidance on the regimen including the need of treatment and risk associated with discontinuation of treatment at the first visit. b. Measures to reduce the amount to be born by the individual in the medical expenses. c. Preparation of a pamphlet for therapeutic guidance in foreign languages. PMID- 8497121 TI - [Incidence of pulmonary tuberculosis among workers of NTT in Tokyo area--annual transition by sex and age]. AB - We investigated incidence of pulmonary tuberculosis for 31 years (from 1960 to 1990) by sex and age among workers of NTT (Nippon telegraph and telephone corporation) in Tokyo area. Annual transition of recent years was mainly analyzed and following results were obtained. (1) Incidence in male of the twenties, thirties and forties decreased smoothly from 1960 to around 1980, then came to standstill and increase tendency was suspected, that is to say, 1) incidence in male of the twenties was minimum in 1976 (21 per 100,000 persons). Annual reduction rate (minus means decrease, plus means increase) from 1960 to 1976 was 11.7% and that from 1977 to 1990 was -0.4%. 2) incidence in male of the thirties was minimum in 1983 (0 per 100,000 persons). Annual reduction rate from 1960 to 1982 was -8.8% and that from 1984 to 1990 was +6.8%. 3) incidence in male of the forties was minimum in 1981 (0 per 100,000 persons). Annual reduction rate from 1960 to 1980 was -11.5% and that from 1982 to 1990 was +1.3%. (2) Incidence in male of the fifties decreased gradually from the 1960's and no tendency of increase was observed. (3) Incidence in female of the twenties, thirties and forties decreased almost continuously from 1960 to 1990 and no tendency of increase was observed in each age group, but total incidence in female (from the teens to the sixties) seemed to be leveling off after 1979. From these results, stagnant or increase tendency of pulmonary tuberculosis in young and middle-aged male was noticed. PMID- 8497122 TI - [A case of streptomycin-induced lupus]. AB - A case of streptomycin-induced lupus occurring in a 48-year-old female is presented. She was admitted to our hospital in July 1990, complaining of productive cough and general fatigue. A chest roentgenogram showed cavitary lesions and infiltrative shadows in the bilateral upper and middle lung fields and a sputum smear tested positive for acid-fast bacilli. She was diagnosed as lung tuberculosis and antituberculous therapy with isoniazid, rifampicin and streptomycin was started. Ten days after starting the treatment, she began to complain of high fever and erythema on her face and forearms. Blood cell count revealed leucopenia. The antinuclear antibody and antihistone antibody were positive. The improvement of clinical findings and the lowering of antinuclear antibody titer seen after stopping streptomycin confirmed the diagnosis as streptomycin-induced lupus. Streptomycin-induced lupus is very rare. PMID- 8497123 TI - [Bacteriological examination of acid-fast bacilli]. PMID- 8497124 TI - Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion. AB - The genes for several endothelial-leukocyte adhesion molecules implicated in the initiation of the atherosclerotic lesion contain functional NF-kappa B binding sites which are required for cytokine induction in endothelial cells. Activation of this pleiotropic family of transcription factors may explain in part the diversity of growth factor and cytokine gene expression associated with dysfunctional endothelium, as well as the increased endothelial cell replication observed at lesion prone anatomic sites. Endothelial oxidant stress and activation of the NF-kappa B family of transcription factors may link the otherwise seemingly diverse risk factors associated with the initiation of the atherosclerotic lesion into a final common pathway for induced endothelial gene activation. PMID- 8497125 TI - Immunocytochemical localization of basic fibroblast growth factor in carcinomas and inflammatory lesions of the human digestive tract. AB - BACKGROUND: Basic fibroblast growth factor (bFGF) is one of the important angiogenic peptides. Clarification of its localization in human cancer and inflammatory diseases is important for the study of angiogenesis. EXPERIMENTAL DESIGN: Sliced human gastrointestinal carcinomas and inflammatory lesions were frozen after fixation. Immunocytochemical localization of bFGF was studied at the light and electron microscopic levels. RESULTS: In gastric carcinoma of the diffuse type, bFGF was mainly observed in some of the endothelial cells of the microvasculature and in fibroblasts. Gastric carcinoma of the intestinal type and colonic carcinoma showed the immunoreactivity in fibroblasts, vascular endothelial cells, and in the extracellular matrix (ECM). Carcinoma cells were occasionally positive. In inflammatory lesions, bFGF was most prominent in the ECM. Areas of deposition of bFGF in the ECM partly corresponded to areas of increased immunoreactivity for heparan sulphate proteoglycan. Immunoelectron microscopically, bFGF was localized in the cytosol of fibroblasts and cancer cells but no localization was observed in the lumen of rough endoplasmic reticulum or perinuclear space in any of the cells observed. bFGF was also localized along the luminal surface of vascular endothelial cells, in nuclei of fibroblasts, vascular endothelial cells, smooth muscle cells, and some cancer cells, and in the ECM. CONCLUSIONS: Extensive localization of bFGF in the ECM was related to the areas of increased vascular permeability and active angiogenesis. In cancer tissues, the distribution pattern of bFGF supports a paracrine mechanism among mesenchymal cells rather than a direct paracrine mechanism on vascular cells from carcinoma cells. Nuclear localization of bFGF may support its activity as a transcriptional factor. PMID- 8497126 TI - Loss of expression of fodrin (a structural protein) in cystic changes of human breast. AB - BACKGROUND: Formation of cysts in the human female breast remains a common clinical problem with few pathogenic theories suggested, and none proven. EXPERIMENTAL DESIGN: We studied the immunohistochemical distribution of a structural protein, fodrin (a nonerythroid spectrin) within benign conditions of the breast. RESULTS: Whereas normal breast epithelium expressed fodrin, all breast cysts were consistently negative for fodrin expression. Both larger, tension cysts as well as the smaller microcysts seen in a special pattern of lobular atrophy were uniformly negative. CONCLUSIONS: Lack of fodrin may be a secondary event in cystic alterations of the breast. However, loss of this structural protein may be responsible for altered structural integrity of breast acini, resulting in or fostering the formation of cysts. PMID- 8497127 TI - Vascular adventitial cell expression of collagen I messenger ribonucleic acid in anti-glomerular basement membrane antibody-induced crescentic nephritis in the rabbit. A cellular source for interstitial collagen synthesis in inflammatory renal disease. AB - BACKGROUND: Scarring in the interstitial compartment of the renal cortex heralds a poor prognosis in many forms of renal injury, however, the mechanism through which glomerular inflammation leads to interstitial scarring is not understood. In a model of anti-GBM disease in the rabbit, development of crescentic glomerulonephritis is associated with marked interstitial fibrosis and decreased renal function. We previously demonstrated that collagen accumulation in the model was preceded by increases in collagen I and IV mRNA and that these changes were primarily extraglomerular at early time points when inflammation was predominantly intraglomerular. In order to identify the cellular origins of extraglomerular collagen synthesis in this model, in situ hybridization using an alpha 2(I) procollagen probe was performed. EXPERIMENTAL DESIGN: A 602 bp rabbit alpha 2(I) procollagen cDNA was cloned using a PCR strategy and sequenced. The nucleotide sequence of the coding region was 94% identical with the human alpha 2(I) procollagen sequence. Northern blots were performed to define conditions of specific hybridization of the anti-sense riboprobe. Tissue sections from normal rabbit kidneys and from kidneys 4, 5, 7, 10 and 14 days after injection of anti GBM antibody were hybridized with 35S-labeled sense and anti-sense riboprobes. Cells containing alpha 2(I) mRNA were identified by autoradiography and mRNA abundance was quantitated by grain density. RESULTS: No specific hybridization was detected with the sense probe at any time. alpha 2(I) mRNA was undetectable with the anti-sense probe in normal kidney sections. In contrast, the anti-sense probe hybridized specifically at all time points after induction of anti-GBM disease. In agreement with previous filter hybridization studies, on day 4, when inflammation was predominantly intraglomerular, cells in the periarterial adventitial compartment of renal cortex hybridized strongly. At later time points, labeling was also present in the interstitial spaces, the periglomerular region, in Bowman's space and in the glomerular tuft itself. CONCLUSIONS: We conclude that perivascular adventitial cells are among the first to respond to glomerular inflammation and represent a pool of cells that subsequently contribute to interstitial and glomerular scarring. PMID- 8497128 TI - Confocal laser scanning immunofluorescence microscopy of the pulmonary surfactant system. Association of surfactant protein A with the nucleus of the alveolar type II cell. AB - BACKGROUND: Localization of surfactant protein A (SP-A) to nucleus of type II cells isolated from the lungs of rats has been reported. Data suggested that most SP-A was located within lamellar bodies of the type II cell; however, some SP-A was found in other cytoplasmic regions of the cell and in particular in the nucleus. EXPERIMENTAL DESIGN: Type II cells and type II cell nuclei isolated from the lungs of rats were reacted with affinity-purified antibodies against SP-A. Location of SP-A was determined by using fluorescein isothiocyanate-labeled secondary antibodies and the distribution of fluorescence examined by using a laser scanning microscope fitted with a confocal aperture. Two-dimensional electrophoresis followed by Western blotting was used to separate and identify type II cell nuclear proteins. RESULTS: Nuclei were isolated from type II cells obtained from elastase-digested rat lungs and examined for the presence of SP-A. The nuclei contained both focal and diffuse deposits of SP-A. Some regions within the nuclear matrix (in particular the nucleolus) appeared to be relatively devoid of SP-A. The perinuclear membrane stained intensely for SP-A where optical sectioning showed its presence as a patchwork of punctate deposits. Analysis of the SP-A associated with the nucleus by two-dimensional electrophoresis revealed that it consisted of a family of proteins with molecular masses of 26, 32, and 36 kDa and pI 5.1. Biosynthesis of nuclear SP-A in primary cultures of type II cells was sensitive to inhibitors of glycosylation resulting in the presence of only the lowest molecular weight unprocessed form. CONCLUSIONS: These data indicate that three basic forms of SP-A are associated with the nucleus of the type II cell and are especially concentrated on the perinuclear membrane. PMID- 8497129 TI - Noninvasive microscopic evaluation of the intact living nephrotic kidney. AB - BACKGROUND: Tandem Scanning Confocal Microscopy (TSCM) is a new form of microscopy that allows one to noninvasively "optically section" into intact structures and record microscopic images in real-time. In this study, we have evaluated the ability of this new technology to distinguish histopathologic changes in unstained living kidneys that occur coincident with the onset of puromycin aminonucleoside-induced nephrosis. EXPERIMENTAL DESIGN: The rats were anesthetized and a laparotomy was performed to expose the kidneys. Using a TSCM equipped with a 24x water-immersion objective, we viewed and recorded real-time images of subcapsular living uriniferous tubules and glomeruli of puromycin aminonucleoside-induced nephrosis rats exhibiting different levels of proteinuria. RESULTS: TSCM revealed a variety of histopathologic changes in the puromycin aminonucleoside-induced nephrosis uriniferous tubules including dilation of proximal tubular lumens, loss of microvillous brush border, cellular debris in the tubule lumens, and focal regions of extensive tubular necrosis. Using the fluorescent probe carboxyfluorescein, we were able to demonstrate significant heterogeneity in the movement of this fluorescent probe through the uriniferous tubules (e.g., some tubules were completely blocked), and irregular patterns in flow of carboxyfluorescein through nephrotic glomeruli. CONCLUSIONS: These observations indicate that TSCM is capable of revealing a variety of histopathologic changes in unstained, intact, living kidneys. In addition, many of the histopathologic features of the uriniferous tubules revealed by TSCM are difficult or impossible to distinguish in biopsied samples of renal tissue. PMID- 8497130 TI - Dr. Christopher Graham, early Mayo partner. PMID- 8497131 TI - Multiplane transesophageal echocardiography: image orientation, examination technique, anatomic correlations, and clinical applications. AB - Multiplane transesophageal echocardiography (TEE) consists of a single ultrasound array or imaging sector that can be rotated around the long axis of the ultrasound beam typically in a 180 degrees arc. This capability produces a circular (conical) continuum of tomographic two-dimensional images. The principal advantage of multiple TEE is that the transducer can be rotated to an image specific orientation and critically optimized. Thus, manipulation of the transducer is less complex than with the biplane technique, and user adaptation is considerably enhanced. The logical image notation (that is, degrees of rotation) and orientation are described in this report. A step-by-step approach to the multiplane TEE examination, which evolved from our initial experience with 400 consecutive patients, is correlated with accompanying tomographic anatomic corroboration. The unique clinical applications are discussed and related to the amplification of diagnostic information. Although the multiplanar TEE transducer is relatively large, all adult patients who weigh 40 kg or more can be examined. No major complications occurred in our initial experience with this promising new technology. PMID- 8497132 TI - Transfrontal orbital decompression after failure of transantral decompression in optic neuropathy of Graves' disease. AB - Transantral and transfrontal orbital decompression procedures are effective for treating optic neuropathy of Graves' disease. We studied 10 patients with Graves' disease to clarify whether transfrontal decompression is effective after prior failure of transantral orbital decompression. All patients had persistent or recurrent optic neuropathy after transantral decompression and had failed to respond to systemic corticosteroid therapy. After transfrontal decompression, visual acuity improved in 70% of the eyes, and visual field scotomas decreased in 80%. No major intraoperative or postoperative complications occurred. We conclude that in optic neuropathy of Graves' disease, transfrontal orbital decompression after failure of transantral decompression is an acceptable and beneficial salvage procedure. PMID- 8497133 TI - Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis. AB - We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis. PMID- 8497134 TI - Vertebral compression fractures sustained during golfing: report of three cases. AB - Considerable concern has been expressed about the type and level of exercise that are safe for women with osteopenia and osteoporosis; however, published information on the effect of golfing on the osteoporotic spine is meager. We describe three postmenopausal patients with acute compression fractures of the vertebrae that occurred during midswing while golfing. These healthy, active women were long-term golfers; their ages at the time of the trauma were 63, 58, and 66 years. In one patient (case 1), osteoporosis was diagnosed before the golf related injury. The two other patients (cases 2 and 3) sought medical attention after the trauma and were found to have osteoporosis. The bone mineral density of the lumbar vertebrae (L2-4) in the three patients at the time of or shortly after the trauma was as follows: case 1, 0.77 g/cm2 (3rd percentile of normal, corrected for age); case 2, 0.63 g/cm2 (less than 1st percentile of normal, corrected for age); and case 3, 0.69 g/cm2 (2nd percentile of normal, corrected for age). These findings raise the issue of the safety of golfing for women with previously diagnosed osteoporosis and for those with predisposing risk factors for the disease. Research studies of the kinematics and kinetics of the spine during the golf swing should be conducted. In the interim, a rigid back support for golfers with osteoporosis may be helpful until more conclusive evidence is available from controlled trials. PMID- 8497135 TI - Functional endoscopic sinus surgery: an overview. AB - "Functional endoscopic sinus surgery" is a minimally invasive technique for treating chronic and acute sinusitis. It is based on the concept that most diseases of the paranasal sinuses are due to obstruction of the anterior ethmoid cells in the region of the middle meatus. With use of surgical treatment of the ethmoid sinus and endoscopic instrumentation, chronic and acute sinus disease can be managed; associated morbidity is minimal. Thus, the need for radical resection of the ethmoid sinus and the Caldwell-Luc operation has decreased. Herein the origins and anatomic basis of endoscopic sinus surgery are described, and some current applications in the management of diseases of the paranasal sinuses are reviewed. PMID- 8497136 TI - Cerebral transplantation for Parkinson's disease: current progress and future prospects. AB - Cerebral transplantation has received considerable attention from both the medical community and lay press as a potential treatment for Parkinson's disease. Animal models have demonstrated feasibility, although the experience in subhuman primates was very limited when the first human trials were initiated in the mid 1980s. The dramatic success reported for adrenal-to-brain transplantation in some initial trials could not be consistently replicated by other centers. Occasionally, however, patients benefited. Failure of the adrenal medullary graft to survive may have been a major factor in the poor outcomes. Recently, several US and European centers reported substantial clinical improvement after fetal dopaminergic mesencephalon was grafted into the striatum of patients with Parkinson's disease. Although many outcomes were impressive, in some cases the improvement was marginal; in no case was the condition completely reversed, and all but one patient still required levodopa therapy. Before this technique can be considered for routine use, further refinement is necessary, and many technical issues must be addressed. Certain animal studies have suggested that transplantation-related improvement may be derived from graft neurotrophic factors rather than from secretion of dopamine into the dopamine-depleted brain of patients with Parkinson's disease. Preliminary investigations in animals indicate that several other tissues, besides fetal mesencephalon, may also prove appropriate for grafting. Ultimately, advances in molecular biology may allow either transplantation of genetically engineered cells or direct modification of existing brain cells by transfection with viral vectors. The favorable preliminary experience with cerebral transplantation in patients with Parkinson's disease has resulted in the consideration of this strategy for other neurologic disorders. PMID- 8497137 TI - Ultrasound-guided compression and repair of postangiographic femoral arteriovenous fistulas. PMID- 8497138 TI - Stress among medical oncologists: the phenomenon of burnout and a call to action. PMID- 8497139 TI - Management of Graves' ophthalmopathy with optic nerve involvement. PMID- 8497140 TI - Lipid and lipoprotein fractions and coronary artery disease. PMID- 8497141 TI - Good Samaritan laws. PMID- 8497142 TI - Cutaneous paraneoplastic syndromes associated with lung cancer. PMID- 8497143 TI - [Evaluation of various criteria for the interpretation of western blot for the diagnosis of human immunodeficiency virus infection. Spanish Group for the Study of HIV-2]. AB - BACKGROUND: The Western blot (WB) is the most commonly used test to confirm the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Different criteria of interpretation of the band profile have been proposed with there being no unanimity as to its reliability. The sensitivity and specificity of several criteria proposed for the interpretation of WB were evaluated and the individual significance of the reactivity of each band of the WB was analyzed. METHODS: The presence of antibodies against HIV-1 was prospectively studied in 8,073 samples of subjects with risk of infection. A total of 1,993 (25%) were reactive by ELISA and 1,261 were analyzed by WB, with a semiquantitative reading of the bands with a point scale from 0 to 2 being performed. The final interpretation of the WB (negative, doubtful, or positive) was carried out following 5 recommendations of usage. A test designed with synthetic peptides (Pepti-lav) was used as a reference and in discordant cases, other more specific serologic tests and/or genetic analysis by polymerase chain reaction (PCR) were performed. RESULTS: In order of frequency, the greater sensitivity was found to be for the CRSS (Consortium for Retrovirus Serology Standardization) criteria (97.9%), OMS (96.6%), CDC (Center for Disease Control) (95.9%), ARC (American Red Cross) (95.6%) and FDA (99.8%). The greatest specificity was for the criteria of the OMS, and FDA (99.8%). In order of frequency, the most frequent bands in HIV-1 + individuals were gp160 (99%), gp120, p24, p31, p55, p68, gp41, and p17 (68%). In non infected individuals, the recognized bands were, in decreasing order, p24, p17, p55, p68, p31, and glucoproteins. CONCLUSIONS: Different criteria of interpretation of the Western blot provide different degrees of sensitivity and specificity. The Western blot is a non standardized, expensive, laborious technique of subjective interpretation which provides an appreciable number of undetermined results. PMID- 8497144 TI - [Transthoracic aspiration punction with ultrafine needle in high risk community acquired pneumonia]. AB - BACKGROUND: The identification of etiologic agents of pneumonias acquired in the community (PAC) with risk factors is difficult. The classical diagnostic methods are not profitable and thus invasive techniques are used. In this study the diagnostic use of an invasive technique such as aspirative transthoracic puncture (ATP) was evaluated in this type of pneumonias. METHODS: In 94 patients of high risk suspect of PAC the ATP was carried out. This was performed with an ultrafine needle (25G) without radioscopic control. In all cases blood cultures, serology (Legionella, Mycoplasma pneumoniae, Coxiella burnetti, Chlamydia psittaci) were performed when atypical clinical manifestations were presented and sputum examination (Gram, Ziehl, culture) was undertaken when possible. RESULTS: The sensitivity of ATP was 36% and increased to 54.6% in cases previously untreated with antibiotics. Specificity was 96.4%. The sensitivity of blood culture was 8% and sputum 13.6%. ATP was well tolerated in 97.9% with complication in only 4 (4.3%). The results of ATP led to changes in treatment in 23.1% of the cases with definitive diagnosis of pneumonia. CONCLUSIONS: Aspirative transthoracic puncture with ultrafine needle without fluoroscopic control was a very well tolerated technique with a minimum number of complications, easy to perform at the patients bedside and was used to modify treatment in 23.1% of the cases. PMID- 8497145 TI - [Drug consumption in diabetes mellitus (III). Trends of hypoglycemic agents use and consumption in Tarragona, Catalonia, and Spain (1988- 1991). Group for the Study of Diabetes in Tarragona]. AB - BACKGROUND: To analyze the evolution of the use of drugs in diabetes, the consumption of hypoglycemic medication in the province of Tarragona, the autonomic community of Catalonia and Spain as a whole, was studied. A qualitative evaluation of the tendencies of prescription, as an indirect index of quality in the health care to diabetics was performed. METHODS: The sales of oral hypoglycemic medication (OH) and insulin (INS) were accounted for in the study environment between 1988-1991. To make consumption uniform a standardized unit of measure was used with defined daily doses (DDD)/1,000 inhabitants/day (Drug Utilization Research Group) of the different groups of drugs. Total consumption was obtained by a primary data source (Intercontinental Medical Statistics), and periodically compared with a secondary source (registry of public prescriptions within Tarragona). RESULTS: A progressive increase in the consumption of hypoglycemic drugs was observed: 16.1 to 21.2 DDD/1,000 inhabitants/day (31%) in Spain; 17.7 to 19.8 (12%) in Catalonia and 19 to 23 (21%) in Tarragona. The increase in consumption of INS in Tarragona (43%) was greater than that of OH (12%). In Catalonia, it was much greater (INS: 23%, OH: 7%) and was parallel in Spain (36% and 30%, respectively). The OH/INS index decreased in Catalonia and Tarragona (1.3 and 1.9 in 1991) and remained practically constant (2.3-2.4) in Spain. A global decrease was produced in the consumption of slow insulins with a significant increase in intermediate, premixed and fast insulins. A growing increase in glibenclamide much greater than the remaining sulphonylureas was seen, in addition there was a persistent and low use (less than 1 DDD/100 inhabitants/day) of biguanides. Significative variations of medication consumption were registered according to the territory analyzed. CONCLUSIONS: From 1988 to 1991 there has been an increase in the use of hypoglycemic drugs. The use of oral hypoglycemics has remained constant in relation to insulins in Spain and in Catalonia and, more so in Tarragona, there is a progressive inclination to the use of insulin. The evolution of consumption suggests important asymmetry in the quality of health care and denotes progression in the global educative offer to diabetics. PMID- 8497146 TI - [Changes in bone mass in hepatic cirrhosis, chronic obstructive pulmonary disease, insulin-dependent diabetes, and primary hyperparathyroidism]. AB - BACKGROUND: Liver cirrhosis, chronic obstructive pulmonary disease (COPD), insulin-dependent diabetes mellitus and primary hyperparathyroidism are frequent diseases which are considered as risk factors for the development of osteoporosis. However, review of the literature has shown that the studies published on the aforementioned are far from conclusive. METHODS: By double energy X-ray absorptiometry the bone mineral density (BMD) of the lumbar spine and neck of the femur were determined in 29 patients with liver cirrhosis, 92 with chronic obstructive pulmonary disease (59 treated with corticoids), 81 with insulin-dependent diabetes mellitus and 30 primary hyperparathyroidism (7 operated). RESULTS: Cirrhotic patients had a normal BMD in both localizations. In patients with COPD, without corticoids, a decrease of 6% was found in the spine and or 13.5% in the neck of the femur while in patients with COPD with corticoids the decrease was of 12% and 7% respectively. Diabetic patients had normal BMD in the spine and a decrease of 6% in the neck of the femur and in patients with hyperparathyroidism a decrease of 6% and normality were found, respectively. CONCLUSIONS: The repercussion of cirrhosis, insulin-dependent diabetes, and primary hyperparathyroidism on bone mineral density is nul or slight. In patients with chronic obstructive pulmonary disease treated with corticoids decrease in density of the spine is approximately that of a standard deviation. In patients with the latter not treated with corticoids a similar decrease is found in the neck of the femur. PMID- 8497147 TI - [The intranasal route. An option with future]. PMID- 8497148 TI - [Patient collaboration]. PMID- 8497149 TI - ["Bolus" and the correct use of the language]. PMID- 8497150 TI - [The future of internal medicine services at regional hospitals of Catalonia: strategic lines within the context of change in health]. PMID- 8497151 TI - [Estimating food consumption: methods and challenges]. PMID- 8497152 TI - [The use of confidence intervals to present the results in biomedical journals]. PMID- 8497153 TI - [Clinical and biochemical manifestations in 3 cases of post-partum thyroid dysfunction]. PMID- 8497154 TI - [Early detection of possible neuropsychologic changes in HIV seropositive hemophiliacs]. PMID- 8497155 TI - [Lymphangioleiomyomatosis and cystic fibrosis: pleurodesis versus lung transplant]. PMID- 8497156 TI - [Systemic lupus erythematosus: a clinical and immunological study of 300 patients]. AB - BACKGROUND: The aims of the present study were to analyze the clinical and immunologic characteristics of a wide group of patients with systemic lupus erythematosus (SLE) and define homogeneous subgroups with their own characteristics. METHODS: A prospective study of 300 patients diagnosed of SLE were studied. These patients were subdivided according to sex, age at the onset of the disease and immunologic profile. The statistical study was carried out by the chi (2), Fisher, Student's t and Mann-Whitney U tests. RESULTS: The series was made up of 266 (89%) females and 34 (11%) males. The mean age at onset of the disease was 31.8 +/- 14.6 years. In 48 (16%) patients the first manifestations appeared after the age of 50. Males were shown to present a lower prevalence of arthritis (59% vs 82% in woman, p < 0.005) and malar rash (29% vs 50%, p < 0.05), but had more cutaneous discoid lesions (18% vs 3% p < 0.001). In patients in whom the disease appeared after the age of 50 a lower prevalence of arthritis was presented (67% vs 82% in patients of less than 50 years of age, p < 0.005), malar rash (23% vs 53%, p < 0.001) and nephropathy (21% vs 41%, p < 0.05), but had greater myositis (17% vs 6%, p < 0.01). The absence of antinuclear antibodies (ANA) and the presence of anti-ds DNA and anti-ENA antibodies were associated with differences in the prevalence of different clinical manifestations. CONCLUSIONS: Sex, age and immunologic pattern in systemic lupus erythematosus permit the definition of homogeneous subgroups with their own characteristics: a) males present a lower prevalence of arthritis and malar rash, but a greater prevalence of cutaneous discoid lesions; b) patients over the age of 50 develop arthritis, malar rash and nephropathy with a lower prevalence but have a greater prevalence of myositis; c) patients without antinuclear antibodies and those with anti-ds DNA and anti-ENA antibodies present differences in the prevalences of different clinical manifestations. PMID- 8497157 TI - [Headache in acute cerebrovascular ischemic disease: a prospective clinical study of 195 patients]. AB - BACKGROUND: Headache is a little known aspect in the study of acute ischemic cerebrovascular disease (AICVD). METHODS: To contribute to the knowledge of the clinical characteristics of headache in the different nosologic entities of AICVD a prospective study was performed in 195 patients consecutively studied by CT scan and/or cerebral MRI. RESULTS: There was headache in 32% of the total and in 41% of the thrombotic infarctions, 39% of the cardioembolisms, 26% of the transient ischemic attacks (TIA) and 23% of the lacunar infarcts. The mean duration was 25 +/- 28 hours. Headache was focal in 74% of the cases and of slight or moderate intensity in 74%. Headache was significantly more common in thrombotic infarctions than in lacunar ones (p < 0.05). It was more frequent when the topography is vertebrobasilar (57.5%), in comparison with carotid (21%) or undetermined (17.5%) (p < 0.0001). Headache was more common when topography was cortical (56.5%) in comparison with subcortical (26.5%) (p < 0.005). Eight per cent of the patients presented sentinel headache: 22% of the cardioembolic infarctions, 7% of the lacunars, 6.5% of the TIA and 5.5% of the thrombotic. CONCLUSIONS: Headache in acute ischemic cerebrovascular disease is not uncommon predominating in thrombotic infarctions and cardioembolisms of cortical topography and of vertebrobasilar vascular territory. PMID- 8497158 TI - [Advances and controversies in the study of lacunar syndromes]. PMID- 8497159 TI - [The International System of Units in physiology and pulmonary medicine]. PMID- 8497160 TI - [Fever, hepatosplenomegaly and pancytopenia in a 75-year-old woman diagnosed with systemic lupus erythematosus]. PMID- 8497161 TI - [Idiopathic paralysis of the hypoglossal nerve]. PMID- 8497162 TI - [MALT-type gastrointestinal lymphomas in patients with HIV infection]. PMID- 8497163 TI - [Tuberculous sialadenitis]. PMID- 8497164 TI - [Adenovirus in infantile diarrheas]. PMID- 8497165 TI - [Late candidal endocarditis on a prosthesis in an HIV-positive patient. A good evolution after treatment]. PMID- 8497166 TI - [Diffuse normolipemic plane xanthoma with paraproteinemia, hypocomplementemia and joint involvement]. PMID- 8497167 TI - [Esophageal candidiasis during omeprazole treatment]. PMID- 8497168 TI - [Total creatine kinase (CK), CK-2 and myoglobin in the diagnosis of acute myocardial infarct in an emergency service]. AB - BACKGROUND: In situations with important limitation in the number of beds available the decision of whether to admit a patient with suspected myocardial infarction into a coronary unit is frequently based on certain laboratory tests. METHODS: Two hundred sixty-five patients who went to the hospital for thoracic pain and those for whom the physician on duty requested serum creatinkinase (CK) determination were studied. In addition to total CK, CK-2 and myoglobin were determined in the initial serum sample. The diagnostic performance of these tests was compared with the clinical algorithm developed by Goldman et al to predict the probability of infarction. RESULTS: The prevalence of infarction in the sample was 10%. The number of patients admitted to the ICU represented 26% of those who would have been admitted upon applying the standard criteria. The tests demonstrating the greatest area under the ROC the Goldman et al algorithm (0.78) and myoglobin (0.69). The sensitivity of the laboratory tests was too low to be used as a method of selection. The additional diagnostic information obtained from the myoglobin was of slight relevance when compared to that obtained from the clinical algorithm. CONCLUSIONS: The diagnostic performance of the serum determinations of creatinkinase, creatinkinase-2 and myoglobin does not justify their use as method of patient selection. PMID- 8497169 TI - [The effect of antihypertensive therapy on left ventricular mass and diastolic filling in light and moderate hypertension]. AB - BACKGROUND: To valorate the effect of four antihypertensive drugs on the regression of cardiac mass and diastolic function, by echocardiography-Doppler, in not treated hypertensive subjects. METHODS: 60 mild-moderate hypertensive subjects were studied randomized in four groups of 15 patients each one: enalapril (10-40 mg/d), atenolol (25-100 mg/d), verapamil-retard (120-240 mg/d), alphametildopa (250 mg/8h to 3 g/d). The active drug therapy phase was 6 months, performing echo-Doppler, evaluating posterior-wall and septal-wall thicknesses, ventricular mass index, ratio of early to atrial peak diastolic filling velocity (E/A), the first-third filling fraction and atrial filling fraction. RESULTS: The cardiac mass index decreased with the four drugs: with enalapril from 178 +/- 28 to 155 +/- 29 g/m2 (p < 0.05), with atenolol from 170 +/- 23 to 154 +/- 19 g/m2 (p < 0.05), with verapamil from 180 +/- 27 to 159 +/- 22 g/m2 (p < 0.05) and with alphametildopa from 176 +/- 30 to 142 +/- 22 g/m2 (p < 0.01). The E/A ratio and first-third filling fraction only improved in the atenolol subgroup, from 0.79 +/ 0.13 to 0.97 +/- 0.16 (p < 0.01) and from 36 +/- 5 to 44 +/- 9% (p < 0.01), decreasing atrial filling fraction from 37 +/- 6 to 30 +/- 8% (p < 0.01), without modifying with enalapril (0.74 +/- 0.14 to 0.76 +/- 0.20, 35 +/- 5% to 36 +/- 7%, 38 +/- 5 to 39 +/- 7%, p = NS), verapamil (0.69 +/- 0.12 to 0.74 +/- 0.17, 35 +/- 6% to 36 +/- 8% to 40 +/- 12%, p = NS) neither alphametildopa (0.72 +/- 0.14 to 0.71 +/- 0.21, 34 +/- 5% to 35 +/- 7%, 40 +/- 6% to 41 +/- 9%, p = NS). The heart rate decreased more with atenolol than with the other drugs (61 +/- 15 vs 71 +/- 12, p < 0.01). CONCLUSIONS: In hypertensive patients the decreasing of cardiac mass is not accompanied of improvement of the diastolic function except in patients treated with atenolol, probably due to bradycardia. PMID- 8497170 TI - [The clinical significance of culturing Toxoplasma gondii on blood and other organic media]. AB - BACKGROUND: The aim of this study was to determine the value of the Toxoplasma gondii culture in blood and in other organic fluids in HIV positive and negative patients. METHODS: Retrospective analysis (October 1990-May 1992) was carried out including all patients with positive cultures for T. gondii admitted to the Hospital Central of Asturias. The parasite was identified by monoclonal antibodies against the tachyzoite membrane. All patients with positive cultures were treated with pyrimethamine and sulphadiazine. RESULTS: Three hundred two samples from 256 patients, seropositive and seronegative for HIV, were analyzed. Of the seropositive group 8/45 (18%) had positive cultures for T. gondii versus 9/211 (4.3%) of the seronegative group (p = 0.002). Of the 19 positive samples, 15 were from blood, 3 from bronchoalveolar lavage and one from the vitreous fluid. Four out of 9 patients (44%) with AIDS and encephalic toxoplasmosis (ET) had blood cultures positive for T. gondii. Another 4 patients with AIDS presented toxoplasmenia without visceral involvement. Of the 9 HIV seronegative patients (3 immunodepressed patients), 4 had pulmonary toxoplasmosis, one ocular toxoplasmosis, and other clinical forms of toxoplasmosis were seen in the remaining 4. All the patients evolved to cure except 2 cases coinfected by cytomegalovirus who died. CONCLUSIONS: The identification of Toxoplasma gondii may be performed by blood cultures in half of the patients with AIDS and encephalic toxoplasmosis and in an undetermined percentage of the other clinical forms both in immunocompetent and immunodepressed subjects. In addition, toxoplasmemia has been registered in AIDS patients preceding any other organic seating of the parasite. Early antitoxoplasma therapy may, therefore, be effective. PMID- 8497171 TI - [New prospects in the treatment of hemophilia. High-purity concentrates of factor VIII]. PMID- 8497172 TI - [Informed consent: theory and practice (I)]. PMID- 8497173 TI - [Q fever-induced endocarditis. An analysis of 6 cases]. AB - Endocarditis by Q fever is a diagnostic and therapeutic challenge given the diagnostic delay and elevated morbidity and mortality it carries. Six cases of endocarditis by Q fever attended over the last 7 years were retrospectively studied. Five patients had been previously diagnosed of valvular involvement and three had prosthesis. Five patients presented a febrile syndrome of prolonged duration with negative hemocultures and progressive valvular changes. One patient presented acute valvular failure requiring emergency surgery. The most significant laboratory data were anemia, thrombocytopenia, high ESR and hypergammaglobulinemia. In the echocardiograms valvular vegetations were observed in 4 cases. All the patients received medical treatment with doxicylin, one associated with rifampicin and another cotrimoxazol. In 4 patients valvular reposition was required due to a severe hemodynamic alteration. After a minimum follow up of 2 years all the patients remain asymptomatic. The serologic evolution is described. PMID- 8497174 TI - [The optimization of the results with the use of thrombolytic therapy in acute myocardial infarct (I)]. PMID- 8497175 TI - [Food preferences and aversions in a university population: some reflections on nutrition and dietary compliance]. PMID- 8497176 TI - [Ischemic infarct. Redundancy is not valid]. PMID- 8497177 TI - [Tuberculous meningitis with acellular cerebrospinal fluid]. PMID- 8497178 TI - [Hypertriglyceridemia secondary to bisoprolol treatment]. PMID- 8497179 TI - [Giant-cell arteritis and hypothyroidism]. PMID- 8497180 TI - [Biliary pseudolithiasis due to ceftriaxone]. PMID- 8497181 TI - [The usefulness of the urinary detection of the capsular antigen of Haemophilus influenzae type b in the diagnosis of epiglottitis]. PMID- 8497182 TI - Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. AB - Rat pups 2-14 days of age were exposed daily to handling (15 min of separation from mother and home cage), maternal separation (MS; 180 min of comparable separation), or were left entirely undisturbed (non-handled; NH). As adults, MS rats showed increased hypothalamic corticotropin-releasing factor (CRF) mRNA levels compared with NH rats, while CRF mRNA levels in H rats were significantly lower than either MS or NH animals. Hypothalamic CRF content under basal conditions followed exactly the same pattern. A 20-min period of restraint stress produced significant CRF depletion in all groups, although the percentage of depletion was significantly lower in H animals compared with either MS or NH animals. Restraint stress produced significantly higher increases in plasma corticosterone in MS and NH animals than in H animals. These data reflect the importance of early environmental factors in regulating the development of the hypothalamic CRF system and the responsiveness of the hypothalamic-pituitary adrenal axis to stress. PMID- 8497183 TI - Nerve stimulation and denervation induce differential patterns of immediate early gene mRNA expression in skeletal muscle. AB - Many properties of skeletal muscle cells are closely regulated by motor nerves. Neuromuscular synaptic transmission (including the 'activity' it triggers) mediates many of these effects, while denervation results in a different spectrum of muscle cell changes. However, little is known about the early regulatory events that occur in mature muscle cells in response to muscle activity or denervation. We have examined the effects of motor nerve stimulation and denervation on the expression of 4 immediate early genes (IEGs)--c-jun, junB, zif268, and nur77--in mature mouse gastrocnemius muscle. Electrical stimulation of the sciatic nerve in a pattern of brisk intermittent exercise induced a marked rise in zif268 and c-jun mRNA levels within 45 min, a minimal rise in junB, and no change in nur77 mRNA levels. By contrast, surgical denervation resulted in a marked increase of c-jun, a slight rise in junB, and no change in nur77 or zif268 mRNA levels. These findings show that neural stimulation and denervation lead to differential patterns of IEG expression. The selectivity of these patterns suggests that differential IEG expression may play an important role in regulating the specific phenotypic changes in skeletal muscles that result from denervation, innervation, and various patterns of stimulation. PMID- 8497184 TI - Transplantation of fetal nigral cells reverses the increase of preproenkephalin mRNA levels in the rat striatum caused by 6-OHDA lesion of the dopaminergic nigrostriatal pathway: a quantitative in situ hybridization study. AB - Unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine (DA) pathway causes a significant increase of preproenkephalin (PPE) messenger RNA (mRNA) levels in the DA-depleted striatum in rat brain. Using an in situ hybridization (ISH) technique and computer-assisted microdensitometry, we quantified the changes in PPE mRNA levels in the striatum. Seven months after lesion, levels of PPE mRNA were 75% higher in the DA-depleted striatum than in the contralateral control striatum of the same animal or in the striatum of sham control animals. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a complete reversal of this increase and, in grafted animals, levels of PPE mRNA were at control values. Moreover, this reversal extended beyond the areas reinnervated by the grafted dopaminergic neurons. PMID- 8497185 TI - Glucocorticoid receptor gene expression is unaltered in hippocampal neurons in Alzheimer's disease. AB - Excessive glucocorticoid levels increase the metabolic vulnerability of hippocampal neurons to a wide variety of insults. Since glucocorticoid hypersecretion occurs in Alzheimer's-type dementia it has been proposed that a primary reduction in hippocampal glucocorticoid receptor expression leads to failure of feedback, hypercortisolemia and hence further neuronal loss. However, we have recently found that lesions of the cholinergic innervation of the hippocampus--known to be severely affected in Alzheimer's disease--increase corticosteroid receptor gene expression in the rat hippocampus. We have now examined both glucocorticoid (GR) and mineralocorticoid (MR) receptor gene expression in individual neurons in human postmortem hippocampus, using in situ hybridization histochemistry in 5 patients with Alzheimer's disease (81 +/- 3 years) and 7 controls (81 +/- 7 years) without neurological disease. The distribution and intensity of MR and GR mRNA expression in the hippocampus of Alzheimer's disease were similar to that in control tissue, with high expression in dentate gyrus and CA2-4, but significantly lower expression in CA1. In a separate group of patients with Alzheimer's disease we found significantly increased 24 h integrated plasma cortisol levels (59% greater than age-matched controls) and reduced cortisol-binding globulin (21% lower). These data do not suggest a primary deficiency of biosynthesis of hippocampal corticosteroid receptors in Alzheimer's disease. The maintenance of hippocampal GR and MR gene expression, in the face of an increased glucocorticoid feedback signal, may reflect loss of the cholinergic innervation. PMID- 8497186 TI - Cellular specificity and regional distribution of amyloid beta protein precursor alternative transcripts are unaltered in Alzheimer hippocampal formation. AB - Studies comparing the expression of the amyloid beta protein precursor (APP) gene in brains of patients with Alzheimer's disease (AD) and control individuals have resulted in contradictory findings indicative of selective reductions and relative increases of APP alternative transcripts in AD brain. It has been suggested that changes in APP expression in relation to AD neuropathology may represent highly specific and localized events involving only select populations of cells in particular brain regions. For example, reported AD-related alterations in ratios of APP alternative transcripts could be attributed to changes in expression of APP in specific neuronal subpopulations, and/or reactive astrocytes and/or microglia. To address this question, we have employed in situ hybridization using biotinylated oligonucleotide probes designed to localize specific APP mRNA transcripts in the hippocampal formation of AD patients and age matched controls since this method allows a clear distinction of the classes of neurons and glia containing a particular message.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497187 TI - Mitochondrial transcription: is a pattern emerging? AB - Despite the striking similarities of RNA polymerases and transcription signals shared by eubacteria, archaebacteria and eukaryotes, there has been little indication that transcription in mitochondria is related to any previously characterized model. Only in yeast has the subunit structure of the mitochondrial RNA polymerase been determined. The yeast enzyme is composed of a core related to polymerases from bacteriophage T7 and T3, and a promoter recognition factor similar to bacterial sigma factors. Soluble systems for studying mitochondrial transcript initiation in vitro have been described from several organisms, and used to determine consensus sequences at or near transcription start sites. Comparison of these sequences from fungi, plants, and amphibians with the T7/T3 promoter suggests some intriguing similarities. Mammalian mitochondrial promoters do not fit this pattern but instead appear to utilize upstream sites, the target of a transcriptional stimulatory factor, to position the RNA polymerase. The recent identification of a possible homologue of the mammalian upstream factor in yeast mitochondria may indicate that a pattern will eventually be revealed relating the transcriptional machineries of all eukaryotic mitochondria. PMID- 8497188 TI - SycE, a chaperone-like protein of Yersinia enterocolitica involved in Ohe secretion of YopE. AB - Pathogenic yersiniae secrete a set of 11 anti-host proteins called Yops. The yop genes, scattered around the pYV plasmid, constitute a thermoinduced regulon controlled by the product of virF gene. The secretion of the Yops also requires the presence of the products of the other vir genes and operons, namely virA, virB and virC. The large virC operon and presumably some genes of the virA region encode a new secretion system. Mutations in any of these vir genes impair the production of all the Yops. In contrast, mutations in the yerA locus, located close to yopE, specifically abolish the expression of the cytotoxin YopE. We describe here the counterpart of yerA in Yersinia enterocolitica W22703. We demonstrate that the gene product of yerA regulates the production of YopE at a post-transcriptional level. It specifically binds the YopE protein. We consider that it acts as a specific chaperone and we call it SycE (for specific YopE chaperone). We hypothesize that SycE is a link between translation and the specific Yop export machinery. It is the first representative of a new family of pYV-encoded proteins. PMID- 8497189 TI - Sucrose-derived exopolysaccharides of Streptococcus mutans V403 contribute to infectivity in endocarditis. AB - We used an isogenic mutant of Streptococcus mutans V403, which differs from the wild-type V403 in genes involved in glucan and fructan production, to examine the importance of these exopolysaccharides as factors affecting infectivity in endocarditis. Rats inoculated with V403 developed endocarditis more frequently than animals inoculated with the mutant strain which produced neither glucan nor fructan (58% versus 12%, P < 0.01). In phagocytosis assays, both strains were found to be associated with the human granulocytes but a greater number of live V403 than of mutant organisms could be recovered. Colony counts recovered from fibrin plates incubated with the mutant were lower than those incubated with V403. These experiments indicate that exopolysaccharides produced by Streptococcus mutans contribute to its infectivity in endocarditis. PMID- 8497190 TI - Organization of the genes necessary for hydrogenase expression in Rhodobacter capsulatus. Sequence analysis and identification of two hyp regulatory mutants. AB - A 25 kbp DNA fragment from the chromosome of Rhodobacter capsulatus B10 carrying hydrogenase (hup) determinants was completely sequenced. Coding regions corresponding to 20 open reading frames were identified. The R. capsulatus hydrogenase-specific gene (hup and hyp) products bear significant structural identity to hydrogenase gene products from Escherichia coli (13), from Rhizobium leguminosarum (16), from Azotobacter vinelandii (10) and from Alcaligenes eutrophus (11). The sequential arrangement of the R. capsulatus genes is: hupR2 hupU-hypF-hupS-hupL-hupM-hu pD-hupF-hupG-hupH-hupJ-hupK-hypA- hypB-hupR1- hypC hypD-hypE-ORF19-ORF20, all contiguous and transcribed from the same DNA strand. The last two potential genes do not encode products that are related to identified hydrogenase-specific gene products in other species. The sequence of the 12 R. capsulatus genes underlined above is presented. The mutation site in two of the Hup- mutants used in this study, RS13 and RCC12, was identified in the hypF gene (deletion of one G) and in the hypD gene (deletion of 54 bp), respectively. The hypF gene product shares 45% identity with the product of hydA from E. coli and the product of hypF from R. leguminosarum. Those products present at their N-terminus a Cys arrangement typical of zinc-finger proteins. The G deletion in the C-terminal region of hypF in the RS13 mutant prevented the expression of a hupS::lacZ translational fusion from being stimulated by H2 as it is observed in the wild-type strain B10. It is inferred that the HypF protein is a factor involved in H2 stimulation of hydrogenase expression. PMID- 8497191 TI - AUA1, a gene involved in ammonia regulation of amino acid transport in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae the general amino acid (GAP1) permease catalyses active transport of apparently all amino acids across the plasma membrane. GAP1 activity is regulated by control of synthesis and control of activity in response to the nitrogen source supplied; ammonia and glutamine inactivate GAP1 function while proline and urea allow its maximum expression. We have isolated and characterized a gene, AUA1, involved in ammonia regulation of GAP1 activity. AUA1 is not essential for growth but overexpression of the AUA1 transcript in a high copy vector or due to a regulatory mutation, aua1-1, present approximately 10 bp upstream from the start of AUA1 transcription, releases GAP1 activity from ammonia-inactivation without affecting GAP1 transcription. The aua1-1 mutation has no phenotype when ammonia is replaced by proline or glutamate as the nitrogen source or when it is present in a gap1 background. AUA1 expression is itself ammonia repressible in a wild-type strain but not in the aua1-1 mutant. The AUA1 gene sequence contains a unique short open reading frame of 94 codons corresponding to a polypeptide of 11,714 Da. This polypeptide is highly hydrophilic and extremely basic. The AUA1 product shows no significant similarity with any previously known protein sequence. Interestingly, a 10-amino acid segment of AUA1 is directly repeated in the most basic segment of the protein. Possible roles of AUA1 are discussed. PMID- 8497192 TI - Identification of a nitrogen-regulated promoter controlling expression of Klebsiella pneumoniae urease genes. AB - Synthesis of urease by Klebsiella species is known to be induced when the nitrogen source of the growth medium is limiting, suggesting that urease gene expression is controlled by the nitrogen regulatory (ntr) system. This study showed that K. pneumoniae with mutations in either ntrA or ntrC, two integral components of the ntr system, were phenotypically urease-negative. These mutants could be complemented back to a urease positive phenotype with recombinant plasmids encoding the corresponding ntr gene. A series of ure-lacZYA transcriptional fusions, in conjunction with primer extension analysis, identified a DNA region that encoded a nitrogen-regulated promoter. This promoter region controlled transcription of ureD, the first gene in the Klebsiella pneumoniae urease gene cluster, and ureA, a gene that resides immediately downstream of ureD. A high level of transcription from the ureD promoter required NAC, a recently characterized member of the nitrogen regulatory cascade. NAC is a Lys R-like transcriptional regulator that can act at sigma 70 promoters; expression from nac itself is dependent upon NTRA. Therefore, expression of K. pneumoniae urease was dependent upon the nitrogen regulatory cascade, and transcription of at least two urease genes was from a promoter that was positively regulated by NAC. PMID- 8497193 TI - Pleiotropic drug resistance in Streptococcus pneumoniae: the cross-chat hypothesis. PMID- 8497194 TI - Corynebacterium glutamicum arginyl-tRNA synthetase. PMID- 8497195 TI - Characterization of a Bacillus subtilis SecA mutant protein deficient in translocation ATPase and release from the membrane. AB - SecA is the precursor protein binding subunit of the bacterial precursor protein translocase, which consists of the SecY/E protein as integral membrane domain. SecA is an ATPase, and couples the hydrolysis of ATP to the release of bound precursor proteins to allow their proton-motive-force-driven translocation across the cytoplasmic membrane. A putative ATP-binding motif can be predicted from the amino acid sequence of SecA with homology to the consensus Walker A-type motif. The role of this domain is not known. A lysine residue at position 106 at the end of the glycine-rich loop in the A motif of the Bacillus subtilis SecA was replaced by an asparagine through site-directed mutagenesis (K106N SecA). A similar replacement was introduced at an adjacent lysine residue at position 101 (K101N SecA). Wild-type and mutant SecA proteins were expressed to a high level and purified to homogeneity. The catalytic efficacy (kcat/km) of the K106N SecA for lipid-stimulated ATP hydrolysis was only 1% of that of the wild-type and K101N SecA. K106N SecA retained the ability to bind ATP, but its ATPase activity was not stimulated by precursor proteins. Mutant and wild-type SecA bind with similar affinity to Escherichia coli inner membrane vesicles and insert into a phospholipid monolayer. In contrast to the wild type, membrane insertion of the K106N SecA was not prevented by ATP. K106N SecA blocks the ATP and proton-motive force-dependent chase of a translocation intermediate to fully translocated proOmpA. It is concluded that the GKT motif in the amino-terminal domain of SecA is part of the catalytic ATP-binding site. This site may be involved in the ATP driven protein recycling function of SecA which allows the release of SecA from its association with precursor proteins, and the phospholipid bilayer. PMID- 8497196 TI - DNA sequencing and expression of the gene rnb encoding Escherichia coli ribonuclease II. AB - The Escherichia coli ribonuclease II (RNase II) is an exonuclease involved in mRNA degradation that hydrolyses single-stranded polyribonucleotides processively in the 3' to 5' direction. Sequencing of a 2.2 kb MseI-RsaI fragment containing the rnb gene revealed an open reading frame of 1794 nucleotides that encodes a protein of 598 amino acid residues, whose calculated molecular mass is 67,583 Da. This value is in good agreement with that obtained by sodium dodecyl sulphate/polyacrylamide gel electrophoresis of polypeptides synthesized by expression with the T7 RNA polymerase/promoter system. This system was also used to confirm the correct orientation of rnb. Translation initiation was confirmed by rnb-lacZ fusions. The mRNA start site was determined by S1 nuclease mapping. Two E. coli mutants harbouring different rnb alleles deficient in RNase II activity were complemented with the expressed fragment carrying the rnb gene. PMID- 8497197 TI - Cell differentiation of Proteus mirabilis is initiated by glutamine, a specific chemoattractant for swarming cells. AB - Swarming by Proteus mirabilis involves differentiation of typical short vegetative rods into filamentous hyperflagellated swarm cells which undergo cycles of rapid and co-ordinated population migration across surfaces and exhibit high levels of virulence gene expression. By supplementing a minimal growth medium (MGM) unable to support swarming migration we identified a single amino acid, glutamine, as sufficient to signal initiation of cell differentiation and migration. Bacteria isolated from the migrating edge of colonies grown for 8 h with glutamine as the only amino acid were filamentous and synthesized the characteristic high levels of flagellin and haemolysin. In contrast, addition of the other 19 common amino acids (excluding glutamine) individually or in combination did not initiate differentiation even after 24 h, cells remaining typical vegetative rods with basal levels of haemolysin and flagellin. The glutamine analogue gamma-glutamyl hydroxamate (GH) inhibited swarming but not growth of P. mirabilis on glutamine MGM and transposon mutants defective in glutamine uptake retained their response to glutamine signalling and its inhibition by GH, suggesting that differentiation signalling by glutamine may be transduced independently of the cellular glutamine transport system. Levels of mRNA transcribed from the haemolysin (hpmA) and flagellin (fliC) genes were low in vegetative cells grown on MGM without glutamine or with glutamine and GH, but were specifically increased c. 40-fold during glutamine-dependent differentiation. In liquid glutamine-MGM cultures, differentiation to filamentous hyper-flagellated hyper-haemolytic swarm cells occurred early in the exponential phase of growth, and increased concomitantly with the concentration of glutamine from a 0.1 mM threshold up to 10 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497198 TI - Properties of FNR proteins substituted at each of the five cysteine residues. AB - FNR is a transcriptional regulator controlling the expression of a number of Escherichia coli genes in response to anoxia. It is structurally-related to CRP (the cyclic AMP receptor protein) except for the presence of a cysteine-rich N terminal extension, which may form part of an iron-binding, redox-sensing domain in FNR. Site-directed substitution has previously shown that four of the cysteine residues (C20, C23, C29 and C122) are essential for FNR function, whereas the fifth (C16) is not. The FNR protein exists in two forms separable by non-reducing SDS-PAGE, and in studies with altered FNR proteins containing single substitutions at each of the five cysteine residues it was concluded that the faster-migrating form (FNR(27)), possesses an intramolecular disulphide bond linking C122 to one of the cysteines near the N-terminus. FNR(27) was more abundant in aerobic cells but the physiological significance of this was not established. Footprint studies indicated that FNR proteins lacking essential cysteine residues are impaired in their ability to protect FNR sites in the ndh promoter. The non-essential cysteine residue (C16) was identified as the source of the most reactive sulphydryl group and all of the inactive proteins exhibited different sulphydryl reactivities. The iron content of the C122A-substituted protein was much reduced but those of the other proteins were less affected. Electrospray mass spectrometry confirmed the accuracy of the gene-derived amino acid composition of FNR with a mutant protein and it showed that a fraction of the wild-type protein may carry a 78 Da substituent which could not be removed with dithiothreitol or beta-mercaptoethanol. PMID- 8497199 TI - Multisensory activation of the phosphorelay initiating sporulation in Bacillus subtilis: identification and sequence of the protein kinase of the alternate pathway. AB - The phosphorelay is the signal-transduction system recognizing and integrating environmental signals to initiate sporulation. The major signal input to the phosphorelay is an ATP-dependent kinase, KinA, responsible for phosphorylating the SpoOF protein. Mutants lacking KinA, however, still sporulate, suggesting that other kinases can fulfil its role. In order to identify these kinases, genes for kinases were isolated by hybridization using a degenerate oligonucleotide probe designed for common regions of this class of kinases. A gene for a second kinase, KinB, was isolated which gave a sporulation negative phenotype when inactivated in a kinA background. The kinB locus was sequenced and found to be a small operon consisting of the kinB gene and another gene, kapB, transcribed from a single.sigma A.-dependent promoter. Inactivation of either kinB or kapB in a kinA strain led to severe sporulation deficiency. The kinB gene coded for a 47774 M(r) protein with the carboxyl half of this protein highly homologous to the same domain of KinA. The amino-terminal domain of KinB was hydrophobic with six recognizable membrane-spanning regions. The kapB gene coded for a moderately charged, probably soluble, protein of 14,668 M(r) with no homology to any known protein. Genetic evidence suggests that KapB is required either for the function of KinB or for its expression. Although double mutants kinA kinB cannot sporulate and assume a stage 0 phenotype, the SpoA approximately P-dependent regulation of the abrB gene is normal in these strains, suggesting that low levels of SpoA approximately P accumulate even in the absence of both kinases. This accumulation is dependent on functional spo0F and spo0B genes and its source is unknown. The KinA and KinB pathways are the only pathways capable of producing sufficient Spo0A approximately P to allow initiation and completion of sporulation under laboratory conditions. PMID- 8497200 TI - Sensor and regulator proteins from the cyanobacterium Synechococcus species PCC7942 that belong to the bacterial signal-transduction protein families: implication in the adaptive response to phosphate limitation. AB - A 1.2kb DNA fragment was cloned from Synechococcus sp. PCC7942, which is able phenotypically to complement a phoR creC Escherichia coli mutant for the expression of alkaline phosphatase. A 2.5 kb DNA fragment encompassing the putative gene was then cloned and its complete nucleotide sequence determined. Nucleotide sequencing revealed that the intact gene encodes a protein of 46,389 Da, and that the deduced amino acid sequence shows a high degree of homology to those of the bacterial sensory kinase family. In the determined nucleotide sequence, another gene was adjacently located, which encodes a protein of 29,012 Da. This protein shows a high degree of homology to those of the response regulator family. Thus, we succeeded in the cloning of a pair of genes encoding the sensory kinase and response regulator, respectively, in a cyanobacterium. Mutant strains that lack these genes were constructed, and demonstrated to be defective in their ability to produce alkaline phosphatase and some inducible proteins in response to phosphate-limitation in the medium. These results are probably involved, either directly or indirectly, in the signal-transduction mechanism underlying regulation of the phosphate regulon in Synechococcus sp. PCC7942. Hence, the genes encoding the sensory kinase and response regulator were designated as sphS and sphR, respectively (Synechococcus phosphate regulon). The SphS protein was demonstrated in vitro to undergo phosphorylation in the presence of ATP. PMID- 8497201 TI - [The microbiocenosis of the skin of the hands in the workers of a mechanical engineering plant]. AB - Microbiocenosis of skin on hands of 160 men aged 16-60 (of them 40 healthy men not dealing with production (control) and 120 workers of the combine plant) has been studied. The level of bacterial dissemination of persons of the control group has been stated to vary within 3.62 +/- 0.07-3.78 +/- 0.08 1g KOE/lm2. This level in workers of the assembling and metal-working shops essentially decreases and depends on the peculiarities of the production process. The constant contact of skin on hands with oil causes an increase in the amount of bacteria and the contact with emulsions, on the contrary, promotes their decrease. Among the different ecological groups of microorganisms on skin of hands in workers staphylococci occupy a dominating position. The species composition of the latter is nonuniform in workers of different shops. The high level of contamination of skin on hands by Staphylococcus aureus belonging, mainly, to the second phage group has been determined. PMID- 8497202 TI - [The kinetic and functional characteristics of DNA-dependent DNA-polymerases in Acholeplasma laidlawii PG-8]. AB - The kinetic and functional characteristics of I and II forms of DNA-dependent DNA polymerases of Acholeplasma laidlawii PG-8 have been studied. It is stated that I form of DNA polymerase possesses 5'-3'-exonuclease activity and is a typical replicase; II form of DNA-polymerase possesses both 5'-3'-polymerase and 3'-5' exonuclease activity and is, evidently, a reparase. Both forms of enzyme give preference to poly(U)- and poly(A)-matrices having extremely high activity on these polymers. The enzymatic reactions realized by both forms of DNA-polymerases are described by the first-order equation. The calculated Michaelis-Menten constants equaled 180 and 250 microM for I and II forms of polymerases, respectively. It indicates that affinity to substrate in II form of polymerase is one-third higher than in I form of enzyme. PMID- 8497203 TI - [The antagonistic action of aerobic sporulating bacteria on the causative agents of endometritis in cattle]. AB - 247 strains of 14 species of bacteria (genus Bacillus) have been studied for the antagonistic properties relative to a wide range of the cattle endometritis agents which are both museum and isolated by authors under the above pathology. Many species of genus Bacillus showed a pronounced antagonism. Active antagonists can occur in different species. Bacillus subtilis strains are the most active. Multiple antibiotic resistance of endometritis agents has no effect on the antagonistic activity of the spore-forming aerobe strains. It is shown that practically the whole range of the possible bacterial endometritis agents is sensitive to the antagonistic effect of the most active strains of aerobic bacilli. The antagonistic strains promising for further studies have been obtained. PMID- 8497204 TI - [The inhibition of the cellular immune response by Pseudomonas aeruginosa extracts]. AB - Aquatic-phenol trichloroacetic and salt extracts of Pseudomonas aeruginosa have been studied for their effect on hypersensitivity of the delayed type to guinea pig antigen in mice. It is found that salt extracts of wild strains contain thermostable immunosuppressive factors which are of the lipid nature, have high molecular weight and can be inactivated by trichloroacetic acid and phenol. The salt extracts of museum strains as well as aquatic-phenol and trichloroacetic extracts obtained from wild and museum strains had no immunosuppressive activity. PMID- 8497205 TI - [The use of the neustonic forms of bacilli for purifying and decontaminating reservoirs]. AB - It is shown possible to select the bacterial strains which are neuston ones, i.e., concentrating on the water-atmosphere interface. The preparation based on the neuston form of Bacillus megaterium is more efficient for purification of water polluted with oil hydrocarbons than the preparation based on the planktonic form of the same culture. Preparation based on the neuston form of the aerobic spore-forming bacteria is effective for biological decontamination of sewage treated using conventional methods. Application of neuston bacterial forms permits intensifying the microbiological processes in the thin (15-40 microM) surface layer of water bodies. PMID- 8497206 TI - Recombinant antihemophilic factor. PMID- 8497207 TI - Oncoscint for detection of disseminated colorectal and ovarian cancer. PMID- 8497208 TI - Shade UVAGuard--a second broad-spectrum sunscreen. PMID- 8497209 TI - In vivo effects of intravascularly applied Escherichia coli hemolysin: dissociation between induction of granulocytopenia and lethality in monkeys. AB - The effects of intravascular application of endotoxin-depleted Escherichia coli hemolysin (HlyA) was studied in rabbits and monkeys. In rabbits, bolus application of HlyA calculated to effect final blood levels of approximately 2-3 HU/ml (200-300 ng/ml) caused an acute fall of polymorphonuclear blood leukocytes to less than 20% of starting levels within 5 min. Additionally, platelet counts dropped to approximately 30% of starting levels, whereas lymphocyte counts varied considerably and seldom fell to less than 50%. Nine out ten animals that received 2-4 HU/ml toxin died within 90 min post application. These animals presented with signs of acute respiratory failure and post mortem inspection of the internal organs revealed hemorrhagic pulmonary edema. Other internal organs appeared unaffected. Application of less than 1 HU/ml HlyA was never fatal (n = 9), and only transient leukopenia was noted. Monkeys presented with a remarkable and different response. Two animals were repeatedly given HlyA at high doses ranging from 3 to 10 HU/ml. Both animals developed selective granulocytopenia, but following a short, transient drop in blood pressure they showed no severe clinical signs of cardiovascular or pulmonary malfunction. Histological examinations revealed accumulation of polymorphonuclear granulocytes in both animals in liver, lung and spleen. Very high leukocyte elastase levels were measured in one animal over a period of 1.5 h. The present results demonstrate a remarkable tolerance of monkeys towards the leukocidal effects of E. coli hemolysin. Lethality in rabbits must be due to additional effects of the toxin, possibly on cells in the pulmonary vasculature. Neither pulmonary sequestration of granulocytes nor massive release of elastase from these cells is in itself sufficient to provoke pulmonary dysfunction in monkeys. PMID- 8497210 TI - Influence of lactoferrin on the entry process of Escherichia coli HB101 (pRI203) in HeLa cells. AB - Lactoferrin (Lf) is an iron-binding protein which plays an important role in the host defense systems of different mucosal surfaces including the intestinal mucosa. In the present research the role of apo-Lf and iron-saturated Lf in the invasion process of enteroinvasive bacteria, grown in iron stress or excess, was investigated. As enteroinvasive bacterium, Escherichia coli HB101 strain harboring a plasmid which contains the chromosomal inv gene from Yersinia pseudotuberculosis was utilized. The product of this gene (invasin) enables this microorganism to invade human epithelial cultured cells (HeLa). The results obtained showed that apo-Lf and iron-saturated Lf added at physiological concentration during the infection exerted a significant inhibition of adhesion (3.2 x 10(5) instead 3.4 x 10(6) adherent bacteria grown in iron excess; 1.6 x 10(3) instead of 2.3 x 10(4) adherent bacteria grown in iron-limited medium) and internalization (4.0 x 10(5) instead of 3.7 x 10(6) internalized bacteria grown in iron excess; 2.1 x 10(3) instead 2.8 x 10(4) internalized bacteria grown in iron-limited medium). It has also been demonstrated that in these experimental conditions Lf binds to HeLa cell membrane as well as to bacterial outer membrane. It is likely that this binding interfere with the early events of interaction between bacteria and eukaryotic cells. This inhibiting effect of Lf on the invasion efficiency of E. coli HB101 (pRI203) could be related to the cationic nature of the molecule, although other mechanisms cannot be ruled out. PMID- 8497211 TI - The x-ray centennial--Thompsons and Thomsons. AB - When x rays were discovered by Wilhelm Roentgen in November, 1895, the news spread rapidly through Europe, Great Britain, and the United States and many individuals became involved in their development. Some of the more prominent participants shared the name of Thompson or Thomson, which causes confusion when the history of x rays is discussed because of their similar pronunciation. In Britain they were William Thompson (Lord Kelvin), J. J. Thomson, and Silvanus P. Thompson and in the United States it was Elihu Thomson. In addition, one of the first books on x rays published in the United States was written by Edward Thompson. PMID- 8497212 TI - Wall-correction and absorbed-dose conversion factors for Fricke dosimetry: Monte Carlo calculations and measurements. AB - For megavoltage radiotherapy photon beams, EGS4 Monte Carlo calculations show, and experimental measurements confirm with an accuracy of 0.2%, that glass or quartz-walled vials used in Fricke dosimetry increase the dose in the Fricke solution. This is mainly caused by increased electron scattering from the glass which increases the dose to the Fricke solution. The dose perturbation is shown to vary from nothing in a 60Co beam up to 2% in a 24-MV beam. For plastic vials of similar shapes, calculations demonstrate that the effect is in the opposite direction and even at high energies it is much less (0.2% to 0.5%). PMID- 8497213 TI - Calibration of high-energy photon and electron beams for radiotherapy using AAPM 1983 and IAEA 1987 dosimetry protocols. AB - To follow up on the theoretical comparison of the IAEA 1987 and AAPM 1983 protocols for dosimetry calibration of high-energy photons and electrons [Med Phys. 18, 26-35 (1991)], results of a set of dosimetric measurements made with a Farmer type PTW and Capintec ionization chambers in solid water, PMMA, and polystyrene phantoms and exposed to a 4 MV photon beam from a Varian Clinac 4S at Yale, a 10 MV photon beam and 6 and 15 MeV electron beams from a Varian Clinac 1800 at Phelps Radiation Center, University of Connecticut, and a 25 MV photon beam from a Sagittaire at Yale, are presented. Because different methods are used for the determination of electron beam energies, the values of mean electron energy determined by the two protocols are different by up to 8%. However, for dose inter-comparison, the overall agreement between the two protocols is within 1% in most cases, with a maximum discrepancy of 3.3% in one case. For photons, the IAEA results are smaller than the AAPM results by 0.7% on the average, while maximum discrepancies are in the range of -0.4%-(-1%). In the case of 15 MeV electrons, the discrepancies between the two protocols are found to be in the range of -0.1%-1% and have an average value of 0.5%. In contrast to the above, a large discrepancy is observed between the two protocols for 6 MeV electrons. Depending upon the choice of phantom and ion chamber, this discrepancy is found to be in the range of -0.1%-(-3.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497214 TI - A finite element approach for modeling photon transport in tissue. AB - The use of optical radiation in medical physics is important in several fields for both treatment and diagnosis. In all cases an analytic and computable model of the propagation of radiation in tissue is essential for a meaningful interpretation of the procedures. A finite element method (FEM) for deriving photon density inside an object, and photon flux at its boundary, assuming that the photon transport model is the diffusion approximation to the radiative transfer equation, is introduced herein. Results from the model for a particular case are given: the calculation of the boundary flux as a function of time resulting from a delta-function input to a two-dimensional circle (equivalent to a line source in an infinite cylinder) with homogeneous scattering and absorption properties. This models the temporal point spread function of interest in near infrared spectroscopy and imaging. The convergence of the FEM results are demonstrated, as the resolution of the mesh is increased, to the analytical expression for the Green's function for this system. The diffusion approximation is very commonly adopted as appropriate for cases which are scattering dominated, i.e., where mu s >> mu a, and results from other workers have compared it to alternative models. In this article a high degree of agreement with a Monte Carlo method is demonstrated. The principle advantage of the FE method is its speed. It is in all ways as flexible as Monte Carlo methods and in addition can produce photon density everywhere, as well as flux on the boundary. One disadvantage is that there is no means of deriving individual photon histories. PMID- 8497215 TI - Decomposition of pencil beam kernels for fast dose calculations in three dimensional treatment planning. AB - A method for the calculation of three-dimensional dose distributions for high energy photon beams is presented. The main features are (i) the calculation is fast enough to allow interactive three-dimensional treatment planning, and (ii) irregularly shaped or compensated fields, which are required to fit three dimensional dose distributions to target volumes, are adequately taken into consideration. The method is based on the pencil beam convolution technique and shares its features concerning accuracy. A considerable gain in speed is achieved by decomposing the pencil beam kernel into three separated terms, thus reducing the required number of two-dimensional convolutions. The convolutions are performed in the frequency domain via the fast Hartley transform. Using these techniques, the calculation time for the convolutions is only about 8 s on a DEC VAX station 3100. This is one-fourth to one-third of the calculation time for the ray tracing through the three-dimensional CT data set, which has to be performed in any case. Results of the calculation are compared with measurements in a homogeneous phantom for 15 MV photons. Two irregular fields shaped with a multileaf collimator are considered. The deviations between measured and calculated absolute dose values are smaller than +/- 2%. PMID- 8497216 TI - How accurately can EGS4/PRESTA calculate ion-chamber response? AB - Ion-chamber responses are calculated for graphite, PMMA, and aluminum-walled ion chambers free-in-air in 60Co beams and 200-keV beams for a graphite chamber. The EGS4 Monte Carlo system is used with various electron step-size algorithms, in particular the PRESTA algorithm, the much simpler ESTEPE constraint on the energy loss per step, and in combination. Contrary to previous reports, it is found that there are variations in the calculated ion chamber response of up to 3% in 60Co beams and up to 8% in the 200-keV beam. It is recommended that all ion chamber calculations be done with the PRESTA algorithm plus an additional constraint on the energy losses per step of 1% (or less for higher-Z materials). The systematic uncertainty in the calculations for 60Co beams is found to be 1% (1 sigma) and somewhat higher in 200-keV beams because of sensitivity to transport parameters such as AE and ECUT. PMID- 8497217 TI - Experimental verification of a three-dimensional dose calculation algorithm using a specially designed heterogeneous phantom. AB - A solid heterogeneous phantom made up of 25- and 50-mm cubes of materials with different electron densities was used to verify the accuracy of a three dimensional (3-D) dose calculation algorithm. This algorithm uses 3-D information obtained from contiguous CT (computed tomography) slices, spaced 5 mm apart. Primary and scatter doses at a point are calculated by using information from ray tracing CT voxels. The algorithm was developed on a Stardent model 1500 Supergraphic workstation. Cubes of materials with different electron densities were stacked up to simulate finite heterogeneities in three dimensions. This design allows verification of the algorithm for surface contour corrections and finite heterogeneities in the treatment field. Thermoluminescent lithium fluoride chips were placed in grooves milled on the cubes for dose measurement at various points. Different experiments were performed to investigate both the accuracy of the dose calculation algorithm and the utility of the versatile test phantom. PMID- 8497218 TI - Experimental determination of fluence perturbation factors for five parallel plate ionization chambers. AB - The calibration of parallel-plate chambers for absolute dosimetry is an unsettled matter. The medical physics community has not yet agreed on a practical method of obtaining Ngas, although several researchers are working on this problem. If the photon and electron fluence perturbation factors, KwallKcomp, were known for chambers of standard construction with full buildup provision, then an in-air Co 60 calibration could be applied to these, as is done with cylindrical chambers. We have obtained such correction factors for five commercially available chambers based on measurements in air and in homogeneous phantoms relative to matched cylindrical chambers of known dosimetric parameters. For three of the chambers (Markus, Holt and Exradin) we find that KwallKcomp = 1.000 +/- 0.008, in excellent agreement with available results from Monte Carlo calculations. The values for the other two chambers (NACP and Capintec) are different than 1. Our results are compared to recently published values, both calculated and measured. PMID- 8497219 TI - Recombination correction factors for an ionization chamber exposed to discrete patterned pulsed swept beams. AB - An equation for a recombination correction factor for a pulsed swept beam of electrons was derived by Boag. This equation is based on an integration technique, which assumes that a large number of spot beams cover the radiation field, that the field size is much larger than the spot beam size, and that the spot beam size is much larger than the chamber size. However, for computer controlled pulsed swept beams of electrons, the spot beam pattern can be altered, may not cover all of the field area, and the locations are reproducible. In this report, a summation method is proposed for this type of beam. Calculations for two such beams are demonstrated with the chamber located in the center of the field, and with the chamber half-way to and at the edge of the field for a linear accelerator. The results lie between the integration pulsed swept and pulsed beam curves. Moving the ionization chamber from the center toward the edge of the field produces curves closer to the pulsed swept beam curve. Increasing spot beam size produces curves closer to the pulsed beam curves. It is therefore concluded that the pulsed swept beam cannot be characterized by a single recombination correction factor curve. The actual curve will be bounded by the integration pulsed swept and pulsed beam curves. PMID- 8497220 TI - Evaluations of two solid water parallel-plate chambers in high-energy photon and electron beams. AB - Using high-energy photon and electron beams, the response of two solid water parallel-plate chambers is evaluated against a PTW (Physicallsch-Technische Werkstatten) Farmer-type chamber. These two chambers are (1) a Memorial "Holt" chamber which was further modified by this author to take advantage of electrically conductive solid water, and (2) a thin window parallel-plate chamber designed by Attix. The evaluations are made for (1) stability and reproducibility, (2) polarity effect, (3) ion recombination correction, (4) field size dependence on output, (5) dose rate dependence on output, and (6) absorbed dose comparison in high-energy photon and electron beams using the American Association of Physicists in Medicine Task Group 21 (TG21) protocol. PMID- 8497221 TI - Three-dimensional verification of patient placement during radiotherapy using portal images. AB - The use of a single portal image for the three-dimensional verification of patient placement during radiotherapy has been investigated. In this study, a deviation in the patient positioning is quantified by a three-dimensional translation and rotation of the patient. The parameter values are obtained by fitting the projections of anatomical match points in the simulator and the portal image, using the three-dimensional gantry coordinates of these points in the intended treatment setup. Two methods for finding an analytical solution for the fitting problem are presented. One method yields a solution from the affine transformation of the portal image (shift, rotation, magnification, and stretching in a specified direction) that fits the projections of the match points on the simulator image. The second and more accurate method yields a solution that expresses the estimated parameter values and their covariances as functions of image and three-dimensional gantry coordinates of the selected matchpoints. The robustness and sensitivity of the solution is implicitly given by these expressions. The applications of these methods are illustrated by experiments with a human pelvic bone. PMID- 8497222 TI - Scatter factors for a 25-MV x-ray beam. AB - The scatter factors, i.e., the ratios between the primary and scatter components of absorbed dose, have been determined for a 25-MV x-ray beam. The primary dose is described by attenuation and head-scatter factors. The attenuation coefficient decreased from 0.028 cm-1 at the surface to 0.025 cm-1 at 30 cm depth. The head scatter factor varied about 8% for collimator settings from 5 x 5 to 40 x 40 cm2. To determine the scatter factors, measured tissue-output ratios were divided by the attenuation and head-scatter factors for the same depth and field size. The results were fitted, with agreement within +/- 1%, to a model which assumes a linear relation between the scatter factor and the field size if the ratio between field size and depth is constant. The model requires transient electron equilibrium, which is present when the depth exceeds 6 cm and the field size 6 x 6 cm2. The scatter factor increases to 1.33 at 30-cm depth and 40 x 40 cm2 field size. The peak scatter factor (PSF) at 3.5-cm depth reaches 1.06 for the largest field. Both PSF and NPSF, the normalized peak scatter factor, are affected by electron disequilibrium, which causes some conceptual ambiguities and numerical uncertainties. PMID- 8497223 TI - Backscatter into the beam monitor chamber: implications for dosimetry of asymmetric collimators. AB - Backscatter from the asymmetric collimators of a linac into the beam monitor chamber (BMC) has been investigated for two accelerators having different BMC configurations. The effect has been quantified as a function of field size and collimator jaw position for 6 and 18 MV beams. The results indicate a maximum 2.5% (6 MV) and 4% (18 MV) decrease in output in one case and a negligible effect in the other case. The experiments indicate that the difference can be attributed to the different construction of the BMC's for the two accelerators. PMID- 8497224 TI - Dosimetry of large wedged high-energy photon beams. AB - The dependence of the wedge factor and central axis depth dose on field size was evaluated for 6-, 10-, and 24-MV wedged photon beams for field sizes up to 40 x 40 cm2. The wedge factor for 60 degrees, 45 degrees, 30 degrees, and 15 degrees wedges in a 24-MV beam was found to vary by as much as 25%, 12%, 9%, and 5%, respectively, over a field size range of 5 x 5 to 40 x 40 cm2. For 10 and 6 MV wedged beams, the wedge factors varied by up to 17% and 15%, respectively, over the same field size range. The depth dose curves for the wedged beams differed significantly from the open beam profiles. At 6 MV, the wedges caused beam hardening while at 24 MV, with the exception of the 15 degrees wedge, all wedged beams were softer than the open beams, for all field sizes. At 10 MV, wedged fields of size less than 20 x 20 cm2 were hardened relative to the open beam, whereas larger wedged fields had depth dose values within +/- 1% of the 10-MV open-beam depth dose data. Accurate treatment planning for large wedged fields and high-energy photon beams thus requires the use of wedged beam depth dose curves and field size specific wedge factors. It was established that an equivalent square field for a rectangular wedged field can be determined using the standard open beam formulation. The largest difference between the wedge factor for a rectangular beam and its equivalent square beam was 2.5% and occurred for 24-MV elongated fields.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497225 TI - Improving agreement between radiation-delineated field edges on simulation and portal films: the edge tolerance test tool. AB - The anatomy at the edge of a treatment machine portal film may differ from that shown by the delineator lines on a simulator film by up to 10 mm, even if both the simulator and the treatment machine meet accepted criteria for mechanical tolerances. To assure that this possibility is minimized requires some form of overall alignment check between the simulator and the treatment machine. A new test device, the edge tolerance test tool (ET3), has been designed to permit a quick and accurate check on whether portal film disagreement with simulator films is due to an accumulation of tolerances. Its use should eliminate one source of this common problem. PMID- 8497226 TI - Surface dose perturbation due to air gap between patient and bolus for electron beams. AB - The effect of air gaps under bolus material on the surface dose for electron beams is investigated. Dose measurements were performed for air gaps from 0.0 to 3.0 cm and bolus thicknesses of 0.5 and 1.0 cm using the various electron energies and cone sizes available on an electron linear accelerator. Our results show that the surface dose decreases for lower electron energies, smaller field sizes, thicker boluses, and larger air gaps. PMID- 8497227 TI - CT-based simulation with laser patient marking. AB - A CT-based simulator has been assembled based on a commercial CT scanner, virtual simulation software developed at the University of North Carolina and a laser drawing device to transfer the radiation portals from the virtual simulator to the patient. The simulation process can be completed in approximately 1 h; under most cases, the treatment portals can be designed and the patient marked in one session. The device has an inherent accuracy of +/- 1 mm. The portal projection accuracy in clinical cases is observed to be better than 2 mm. PMID- 8497228 TI - Evaluation of a diode detector array for measurement of dynamic wedge dose distributions. PMID- 8497229 TI - Dosimetry for 125I seed (model 6711) in eye plaques. AB - The effect of eye plaque materials (gold backing and silastic seed-carrier insert) on the dose distribution around a single 125I seed has been measured, using cubic lithium fluoride thermoluminescent dosimeters (TLDs) 1 mm on an edge, in a solid water eye phantom embedded in a solid water head phantom. With an 125I seed (model 6711) positioned in the center slot of the silastic insert for a 20 mm plaque of the design used in the collaborative ocular melanoma study (COMS), dose was measured at 2-mm intervals along the plaque central axis (the seed's transverse axis) and at various off-axis points, both with and without the COMS gold backing placed over the insert. Monte Carlo calculations (MORSE code) were performed, as well, for these configurations and closely the same geometry but assuming a large natural water phantom. Additional Monte Carlo calculations treated the case, both for 20- and 12-mm gold plaques, where the silastic insert is replaced by natural water. Relative to previous measurements taken in homogeneous medium of the same material (without the eye plaque), the dose reduction found by both Monte Carlo and TLD methods was greater at points farther from the seed along the central axis and, for a given central-axis depth, at larger off-axis distances. Removal of the gold backing from the plaque did not make measurable difference in the dose reduction results (10% at 1 cm). PMID- 8497230 TI - A simple test phantom for stereotactic computed tomography. AB - An easy-to-use phantom has been constructed for checking the accuracy of a stereotactic computed tomography localization system. This phantom has been used on a commercially available stereotactic radiosurgery system. With this system, the phantom reference point, whose location is established by means of a precision measuring implement, can be localized by a computed tomography (CT) scanner with a standard deviation of measurement that is less than 0.3 mm in three orthogonal axes. PMID- 8497231 TI - Effect of head phantom size on 10B and 1H[n,gamma]2H dose distributions for a broad field accelerator epithermal neutron source for BNCT. AB - The effect of head phantom size on the 10B and 1H[n,gamma]2H dose distributions for a broad epithermal neutron radiation field generated by an accelerator-based epithermal neutron source for boron neutron capture therapy (BNCT) have been studied. Also two techniques for calculating the absorbed gamma dose from a measured gamma-ray source distribution are compared: a Monte Carlo technique, which is well accepted in the BNCT community, and a Point Kernel technique. The count-rate distribution in the central plane of three rectangular parallelopiped head water phantoms irradiated with an epithermal neutron field was measured with a boron trifluoride (BF3) detector. This epithermal neutron field was produced at the Ohio State University Van de Graaff Accelerator Facility. The 10B absorbed dose and the gamma-ray source have the same distribution in the head phantom as the BF3 count-rate distribution. The absorbed gamma dose from the measured source distribution was calculated using MCNP, a Monte Carlo code, and QAD-CGGP, a Point Kernel code. The most pronounced effect of phantom size on 10B absorbed dose was on the dose rate at the depth of maximum dose, dmax. An increase in dose rate at dmax was observed with a decrease in phantom size, the dose rate in the smallest phantom being larger by a factor of 1.4 than the dose rate in the largest phantom. Also, dmax for the phantoms shifted deeper with a decrease in phantom dimensions. The shift between the largest and the smallest phantoms was 6 mm. Finally, the smaller phantoms had lower entrance 10B dose as a percent of the dose at dmax, or better skin sparing. Our calculations for the gamma dose show that a Point Kernel technique can be used to calculate the dose distribution as accurately as a Monte Carlo technique, in much shorter computation times. PMID- 8497232 TI - Air cavity perturbation of a clinical p(42)Be neutron beam. PMID- 8497233 TI - Neutron fluxes in radiotherapy rooms. AB - The spatial distribution of the neutron flux, originated in an electron accelerator therapy room when energies above the threshold of (y,n) and (e,e'n) reactions are employed, is physically due to a direct flux, coming from the accelerator head, and to a flux diffused from the walls. In this work, the flux is described to a high degree of approximation by a set of functions whose spatial behavior is univocally determined by the angular distributions of the neutrons emitted from the shield of the accelerator head and diffused from the walls. The analytical results are verified with an extended series of Monte Carlo simulations obtained with the MCNP code. PMID- 8497234 TI - A geometrically accurate vascular phantom for comparative studies of x-ray, ultrasound, and magnetic resonance vascular imaging: construction and geometrical verification. AB - A technique for producing accurate models of vascular segments for use in experiments that assess vessel geometry and flow has been developed and evaluated. The models are compatible with x-ray, ultrasound, and magnetic resonance (MR) imaging systems. In this paper, a model of the human carotid artery bifurcation, is evaluated that has been built using this technique. The phantom consists of a thin-walled polyester-resin replica of the bifurcation through which a blood-mimicking fluid may be circulated. The phantom is surrounded by an agar tissue-mimicking material and a series of fiducial markers. The blood- and tissue-mimicking materials have x-ray, ultrasound, and MR properties similar to blood and tissue; fiducial markers provide a means of aligning images acquired by different modalities. The root-mean-square difference between the inner wall geometry of the constructed model and the desired dimensions was 0.33 mm. Static images were successfully acquired using x-ray, ultrasound, and MR imaging systems, and are free of significant artifacts. Flow images acquired with ultrasound and MR agree qualitatively with each other, and with previously published flow patterns. Volume-flow measurements obtained with ultrasound and MR were within 4.4% of the actual values. PMID- 8497235 TI - Multiformat video and laser cameras: history, design considerations, acceptance testing, and quality control. Report of AAPM Diagnostic X-Ray Imaging Committee Task Group No. 1. AB - Acceptance testing and quality control of video and laser cameras is relatively simple, especially with the use of the SMPTE test pattern. Photographic quality control is essential if one wishes to be able to maintain the quality of video and laser cameras. In addition, photographic quality control must be carried out with the film used clinically in the video and laser cameras, and with a sensitometer producing a light spectrum similar to that of the video or laser camera. Before the end of the warranty period a second acceptance test should be carried out. At this time the camera should produce the same results as noted during the initial acceptance test. With the appropriate acceptance and quality control the video and laser cameras should produce quality images throughout the life of the equipment. PMID- 8497236 TI - Filter wheel equalization in DSA: simulation results. AB - Digital subtraction angiography (DSA) is a valuable and frequently used diagnostic technique which allows the evaluation of vascular anatomy and pathology. In order to improve the utility and diagnostic performance of DSA, a filter wheel system is presented which can provide mechanically simple, rapidly adaptable, and clinically practical radiographic equalization to DSA images. The filter wheel equalization system consists of a series of computer-driven filter wheels, mounted between the x-ray tube and collimator. Each wheel has an annular area of attenuator material which intersects the x-ray beam and carries a rotationally varying compensation pattern on it. Rotation of the filter wheel modulates the attenuator pattern in the x-ray field under computer control, in a manner designed to increase the x-ray exposure to underexposed areas in the image. A system with eight wheels has 10(19) possible equalization patterns. The compensation patterns are removed in the subtracted DSA images. Computer simulation techniques were used to evaluate various design scenarios for the filter wheel system, using a data base of 191 clinical DSA mask images. For a practical implementation of the filter wheel system, an improvement in the signal to noise ratio of 23%, averaged over the image, was found. PMID- 8497237 TI - A high-resolution XRII-based quantitative volume CT scanner. AB - A laboratory volume CT scanner has been developed, with high spatial resolution in all three dimensions, which can be used for quantitative analysis of excised tissue samples in vitro. The system incorporates an x-ray image intensifier, optically coupled to a time-delay integration (TDI) CCD to obtain low-noise and low-scatter projections of the sample volume. A water bath surrounds the sample to equalize the exposure to the image intensifier, thereby reducing the dynamic range of the input signal. The scanner operates in two modes, producing either a single, transverse image through the sample or a three-dimensional image of the sample volume. Spatial resolution is adjustable over the range of 1.2 to 2.8 mm 1. System response is linear over the range -1000 to 3500 Houndsfield units (HU), with an average precision of +/- 80 HU. The precision of geometric measurements in the transverse plane allows circumference measurements to within +/- 0.1 mm. Finally, applications of this technique of nondestructive analysis in biomedical research are discussed. PMID- 8497238 TI - Optical lumen measurement of coronary artery latex casts. AB - To facilitate calibration and testing of quantitative coronary angiography (QCA) systems, an optical technique has been developed to measure the vessel dimensions of complex coronary artery phantoms. The technique provides accurate geometric data such as centerline position and cross-sectional area of vessel branches. The sequential steps involved in the measurement include taking pictures of different views, tracing magnified images, point-by-point digitizing and computing the center positions and radii along each vessel branch. The accuracy of the optical technique is assessed using the measurement of a precisely known aluminum phantom. Measurement repeatability is assessed by multiple measurement of the same branches on a barium impregnated latex cast which provides a realistic coronary artery phantom. The measurement is demonstrated to be accurate to within 0.01 mm and repeatable to within 0.05 mm on the wire phantom measurement and 0.08 mm on the realistic phantom measurement. PMID- 8497239 TI - A cosine modulation artifact in modulation transfer function computations caused by the misregistration of line spread profiles. AB - Modulation transfer functions (MTFs) are used to analyze the spatial frequency transfer characteristics of medical imaging systems. By definition, accurate MTFs should not include the effects of image noise and they should not be aliased. Therefore, many techniques used to compute MTFs register and average together multiple profiles to improve both signal to noise and/or eliminate aliasing. It is demonstrated that improper registration of individual profiles can cause errors of up to 100% in the MTF. Computer modelling shows that a maximum allowable error of 2% in the MTF requires a registration precision of +/- 1/9 of a pixel for each profile, if the profile was sampled at twice the cutoff frequency of the MTF. One suggested registration method, demonstrated with experimental magnetic resonance image data, is 1.5 times more accurate than the minimum requirement. PMID- 8497240 TI - Rare-earth scatter fractions in chest radiography. AB - A beam stop technique was used to measure the densitometric scatter fractions under three regions of a humanoid chest phantom utilizing LaOBr and Gd2O2S screens. For these receptors, the scatter fractions under the lung and retrocardiac areas were 13%-36% lower than published values for CaWO4. In the mediastinal area, there was no significant difference between the CaWO4 and rare earth phosphors. The use of grids reduces the scatter fraction in all three regions by 40%-75%. With and without a grid, radiographic contrast with Gd2O2S was measured utilizing simulated lesions placed above the lung and retrocardiac areas. PMID- 8497241 TI - Vibrio vulnificus infections associated with raw oyster consumption--Florida, 1981-1992. AB - Vibrio vulnificus is a gram-negative bacterium that can cause serious illness and death in persons with preexisting liver disease or compromised immune systems. From 1981 through 1992, 125 persons with V. vulnificus infections, of whom 44 (35%) died, were reported to the Florida Department of Health and Rehabilitative Services (HRS). This report summarizes data on these cases and presents estimates of the at-risk population in Florida. PMID- 8497242 TI - Epidemic cholera--Burundi and Zimbabwe, 1992-1993. AB - The current cholera pandemic reached sub-Saharan Africa in 1970 and spread rapidly throughout the continent (1). Since then, epidemic cholera has persisted or reemerged in many African countries. This report summarizes cholera outbreaks in Burundi and Zimbabwe and the efforts to control these outbreaks. PMID- 8497243 TI - Ciguatera fish poisoning--Florida, 1991. AB - Twenty cases of ciguatera fish poisoning from consumption of amberjack were reported to the Florida Department of Health and Rehabilitative Services (HRS) in August and September 1991. This report summarizes the investigation of these cases by the Florida HRS. PMID- 8497244 TI - Use of bleach for disinfection of drug injection equipment. PMID- 8497245 TI - A branched signaling pathway for nerve growth factor is revealed by Src-, Ras-, and Raf-mediated gene inductions. AB - A myriad of gene induction events underlie nerve growth factor (NGF)-induced differentiation of PC12 cells. To dissect the signal transduction pathways which lead to NGF actions, we have assessed the relative roles of NGF receptor, Src, Ras, and Raf activities in mediating specific gene inductions. We have used the PC12 cell line as well as sublines which inducibly express activated forms of either Src, Ras, or Raf or a dominant inhibitory form of Ras (p21N17 Ras) to study the expression of multiple NGF-inducible mRNAs. The NGF induction of NGFI A, transin, and VGF mRNAs was mimicked by activated forms of Src, Ras, or Raf and was blocked by p21N17 Ras. The NGF induction of SCG10 mRNA was mimicked only by activated Src and Ras and was blocked by p21N17 Ras, while the induction of Thy-1 mRNA was mimicked only by activated Src and was not blocked by p21N17 Ras. The NGF induction of mRNAs for two sodium channel types was neither mimicked by any activated oncoprotein nor blocked by p21N17 Ras. From these and previous results, we suggest a model in which a linear order of NGF receptor, Src, Ras, and Raf activities is used by NGF to elicit gene inductions. These signaling components define branchpoints in the pathway to specific gene induction events, providing a mechanism for generating a host of diverse NGF actions. PMID- 8497246 TI - Genetic dissection of centromere function. AB - A system to detect a minimal function of Saccharomyces cerevisiae centromeres in vivo has been developed. Centromere DNA mutants have been examined and found to be active in a plasmid copy number control assay in the absence of segregation. The experiments allow the identification of a minimal centromere unit, CDE III, independently of its ability to mediate chromosome segregation. Centromere mediated plasmid copy number control correlates with the ability of CDE III to assemble a DNA-protein complex. Cells forced to maintain excess copies of CDE III exhibit increased loss of a nonessential artificial chromosome. Thus, segregationally impaired centromeres can have negative effects in trans on chromosome segregation. The use of a plasmid copy number control assay has allowed assembly steps preceding chromosome segregation to be defined. PMID- 8497247 TI - Mechanism of cleavage and ligation by FLP recombinase: classification of mutations in FLP protein by in vitro complementation analysis. AB - The FLP recombinase of the 2 microns plasmid of Saccharomyces cerevisiae is a member of the integrase family of site-specific recombinases. Recombination catalyzed by members of this family proceeds via the ordered cleavage and religation of four strands of DNA. Although the amino acid sequences of integrase family members are quite different, each recombinase maintains an absolutely conserved tetrad of amino acids (R-191, H-305, R-308, Y-343; numbers are those of the FLP protein). This tetrad is presumed to reflect a common chemical mechanism for cleavage and ligation that has evolved among all family members. The tyrosine is the nucleophile that causes phosphodiester bond cleavage and covalently attaches to the 3'-PO4 terminus, whereas the other three residues have been implicated in ligation of strands. It has recently been shown that cleavage by FLP takes place in trans; that is, a FLP molecule binds adjacent to the site of cleavage but receives the nucleophilic tyrosine from a molecule of FLP that is bound to another FLP-binding element (J.-W. Chen, J. Lee, and M. Jayaram, Cell 69:647-658, 1992). These studies led us to examine whether the ligation step of the FLP reaction is performed by the FLP molecule bound adjacent to the cleavage site (ligation in cis). We have found that FLP promotes ligation in cis. Furthermore, using in vitro complementation analysis, we have classified several mutant FLP proteins into one of two groups: those proteins that are cleavage competent but ligation deficient (group I) and those that are ligation competent but cleavage defective (group II). This observation suggests that the active site of FLP is composed of several amino acid residues from each of two FLP molecules. PMID- 8497248 TI - Expression of mRNA encoding the macrophage colony-stimulating factor receptor (c fms) is controlled by a constitutive promoter and tissue-specific transcription elongation. AB - The gene encoding the receptor for macrophage colony-stimulating factor 1 (CSF 1), the c-fms protooncogene, is selectively expressed in immature and mature mononuclear phagocytes and trophoblasts. Exon 1 is expressed only in trophoblasts. Isolation and sequencing of genomic DNA flanking exon 2 of the murine c-fms gene revealed a TATA-less promoter with significant homology to human c-fms. Reverse transcriptase primer extension analysis using exon 2 primers identified multiple clustered transcription initiation sites. Their position was confirmed by RNase protection. The same primer extension products were detected in equal abundance from macrophage or nonmacrophage sources of RNA. c-fms mRNA is acutely down-regulated in primary macrophages by CSF-1, bacterial lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). Each of these agents reduced the abundance of c-fms RNA detectable by primer extension using an exon 3 primer without altering the abundance of presumptive short c-fms transcripts detected with exon 2 primers. Primer extension analysis with an intron 2 primer detected products at greater abundance in nonmacrophages. Templates detected with the intronic primer were induced in macrophages by LPS, PMA, and CSF-1, suggesting that each of the agents caused a shift from full length c-fms mRNA production to production of unspliced, truncated transcripts. The c-fms promoter functioned constitutively in the RAW264 macrophage cell line, the B-cell line MOPC.31C, and several nonhematopoietic cell lines. Macrophage specific expression and responsiveness to selective repression by LPS and PMA was achieved by the incorporation of intron 2 into the c-fms promoter-reporter construct. The results suggest that expression of the c-fms gene in macrophages is controlled by sequences in intron 2 that act by regulating transcription elongation. PMID- 8497249 TI - Regulation of proto-oncogene expression in adult and developing lungs. AB - Activation of immediate-early gene expression has been associated with mitogenesis, differentiation, nerve cell depolarization, and recently, terminal differentiation processes and programmed cell death. Previous evidence also suggested that immediate-early genes play a role in the physiology of the lungs (J. I. Morgan, D. R. Cohen, J. L. Hempstead, and T. Curran, Science 237:192-197, 1987). Therefore, we analyzed c-fos expression in adult and developing lung tissues. Seizures elicited by chemoconvulsants induced expression of mRNA for c fos, c-jun, and junB and Fos-like immunoreactivity in lung tissue. The use of pharmacological antagonists and adrenalectomy indicated that this increased expression was neurogenic. Interestingly, by using a fos-lacZ transgenic mouse, it was shown that Fos-LacZ expression in response to seizure occurred preferentially in clusters of epithelial cells at the poles of the bronchioles. This was the same location of Fos-LacZ expression detected during early lung development. These data imply that pharmacological induction of immediate-early gene expression in adult mice recapitulates an embryological program of gene expression. PMID- 8497250 TI - The response of gamma interferon activation factor is under developmental control in cells of the macrophage lineage. AB - Gamma interferon activation factor (GAF) rapidly induces transcriptional activation of gamma interferon (IFN-gamma)-responsive genes. Conversion of the GAF from a latent cytoplasmic to an activated, DNA-binding form is an immediate step in the cellular response to IFN-gamma. The amount of IFN-gamma-activated GAF, measured by exonuclease III protection or gel shift assays, increased strongly upon monocytic differentiation of U937 cells. Activated GAF contained the IFN-responsive 91-kDa protein as its DNA-binding activity in gel shift or exonuclease III assays could be inhibited through direct addition of specific antiserum, and it was not present in p91-immunodepleted extracts. There was a differentiation-induced increase in the amount of nonphosphorylated (latent) p91. Transcription rate measurement demonstrated a strong induction of the p91 gene during monocytic differentiation of U937 cells. The amount of p91 which was rapidly phosphorylated in response to IFN-gamma was found to be much higher in the differentiated cells and suggested a differentiation-controlled increase in the signaling leading to p91 phosphorylation. Concomitantly with a better GAF response, transcriptional activation of IFN-gamma-induced genes and the expression of GAF-dependent, transfected reporter plasmids increased in differentiated U937 monocytes. The promonocyte-monocyte transition also affected the IFN-alpha-responsive transcription factor ISGF-3. Differentiated U937 cells contained more of both the alpha-component p91 and the gamma-component p48, which constitutes the DNA-binding subunit of the complex. Our study thus provides evidence that the synthesis of specific transcription factors can be a regulated event to control the cytokine responsiveness of cells during development. PMID- 8497251 TI - The yeast Cln3 protein is an unstable activator of Cdc28. AB - The Cln3 cyclin homolog of Saccharomyces cerevisiae functions to promote cell cycle START for only a short time following its synthesis. Cln3 protein is highly unstable and is stabilized by C-terminal truncation. Cln3 binds to Cdc28, a protein kinase catalytic subunit essential for cell cycle START, and Cln3 instability requires Cdc28 activity. The long functional lifetime and the hyperactivity of C-terminally truncated Cln3 (Cln3-2) relative to those of full length Cln3 are affected by mutations in CDC28: the functional lifetime of Cln3-2 is drastically reduced by the cdc28-13 mutation at the permissive temperature, and the cdc28-4 mutation at the permissive temperature completely blocks the function of Cln3-2 while only partially reducing the function of full-length Cln3. Thus, sequences in the C-terminal third of Cln3 might help stabilize functional Cdc28-Cln3 association, as well as decreasing the lifetime of the Cln3 protein. These and other results strongly support the idea that Cln proteins function to activate Cdc28 at START. PMID- 8497252 TI - The p53 activation domain binds the TATA box-binding polypeptide in Holo-TFIID, and a neighboring p53 domain inhibits transcription. AB - Antioncogene product p53 is a transcriptional transactivator. To investigate how p53 stimulates transcription, we examined the interaction of p53 with general transcription factors in vitro. We found that p53 binds directly to the human TATA box-binding polypeptide (TBP). We also observed a direct interaction between p53 and purified holo-TFIID, a complex composed of TBP and a group of TBP associated polypeptides known as TAFs. The p53 binding domain on TBP was mapped to the conserved region of TBP, including residues 220 to 271. The TBP binding domain on p53 was mapped to the p53 activation domain between residues 20 and 57. To analyze the significance of the p53-TBP interaction in p53 transactivation, we compared the ability of Gal4-p53 fusion proteins to bind to TBP in vitro and to activate transcription in transient transfection assays. Fusion proteins which bound to TBP activated transcription, and those that did not bind to TBP did not activate transcription to a detectable level, suggesting that a direct interaction between TBP and p53 is required for p53 transactivation. We also found that inclusion of residues 93 to 160 of p53 in a Gal4-p53 fusion repressed transcriptional activation 100-fold. Consequently, this region of p53 inhibits transcriptional activation by the minimal p53 activation domain. Highest levels of activation were observed with sequences 1 to 92 of p53 fused to Gal4, even though this construct bound to TBP in vitro with an affinity similar to that of other Gal4-p53 fusion proteins. We conclude that TBP binding is necessary for p53 transcriptional activation and that p53 sequences outside the TBP binding domain modulate the level of activation. PMID- 8497253 TI - Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. AB - Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. NF-kappa B, consisting of a 50-kDa protein (p50) and a 65-kDa protein (p65), is bound to a cytoplasmic retention protein called I kappa B. Stimulation of cells with a variety of inducers, including cytokines such as tumor necrosis factor and interleukin-1, leads to the activation and the translocation of p50/65 NF-kappa B into the nucleus. However, the in vivo mechanism of the activation process remains unknown. Here, we provide the first evidence that the in vivo mechanism of NF kappa B activation is through the phosphorylation and subsequent loss of its inhibitor, I kappa B alpha. We also show that both I kappa B alpha loss and NF kappa B activation are inhibited in the presence of antioxidants, demonstrating that the loss of I kappa B alpha is a prerequisite for NF-kappa B activation. Finally, we demonstrate that I kappa B alpha is rapidly resynthesized after loss, indicating that an autoregulatory mechanism is involved in the regulation of NF kappa B function. We propose a mechanism for the activation of NF-kappa B through the modification and loss of I kappa B alpha, thereby establishing its role as a mediator of NF-kappa B activation. PMID- 8497254 TI - Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. AB - Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds to core sites in murine leukemia virus and T cell receptor enhancers. Affinity-purified CBF contains multiple polypeptides. In this study, we sequenced five tryptic peptides from two of the bovine CBF proteins and isolated three cDNA clones from a mouse thymus cDNA library encoding three of the tryptic peptides from the bovine proteins. The cDNA clones, which we call CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6, encode three highly related but distinct proteins with deduced molecular sizes of 22.0, 21.5, and 17.6 kDa that appear to be translated from multiply spliced mRNAs transcribed from the same gene. CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6 do not by themselves bind the core site. However, CBF beta p22.0 and CBF beta p21.5 form a complex with DNA-binding CBF alpha subunits and as a result decrease the rate of dissociation of the CBF protein-DNA complex. Association of the CBF beta subunits does not extend the phosphate contacts in the binding site. We propose that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly. PMID- 8497255 TI - The 3' untranslated region of satellite tobacco necrosis virus RNA stimulates translation in vitro. AB - The RNA of satellite tobacco necrosis virus (STNV) is a monocistronic messenger that lacks both a 5' cap structure and a 3' poly(A) tail. We show that in a cell free translation system derived from wheat germ, STNV RNA lacking the 600 nucleotide trailer is translated an order of magnitude less efficiently than full size RNA. Deletion analyses positioned the translational enhancer domain (TED) within a conserved hairpin structure immediately downstream from the coat protein cistron. TED enhances translation when fused to a heterologous mRNA, but the level of enhancement depends on the nature of the 5' untranslated sequence and is maximal in combination with the STNV leader. The STNV leader and TED have two regions of complementarity. One of the complementary regions in TED resembles picornavirus box A, which is involved in cap-independent translation but which is located upstream of the coding region. PMID- 8497256 TI - Mouse heat shock transcription factors 1 and 2 prefer a trimeric binding site but interact differently with the HSP70 heat shock element. AB - To understand the function of multiple heat shock transcription factors in higher eukaryotes, we have characterized the interaction of recombinant mouse heat shock transcription factors 1 and 2 (mHSF1 and mHSF2) with their binding site, the heat shock element (HSE). For our analysis, we utilized the human HSP70 HSE, which consists of three perfect 5'-nGAAn-3' sites (1, 3, and 4) and two imperfect sites (2 and 5) arranged as tandem inverted repeats. Recombinant mHSF1 and mHSF2, which exist as trimers in solution, both bound specifically to this HSE and stimulated transcription of a human HSP70-CAT construct in vitro. Footprinting analyses revealed differential binding of mHSF1 and mHSF2 to the HSP70 HSE. Specifically, mHSF1 bound all five pentameric sites, whereas mHSF2 failed to interact with the first site of the HSE but bound to sites 2 to 5. Missing-nucleoside analysis demonstrated that the third and fourth nGAAn sites were essential for mHSF1 and mHSF2 binding. The binding of the initial mHSF1 trimer to the HSE exhibited preference for sites 3, 4, and 5, and then binding of a second trimer occurred at sites 1 and 2. These results suggest that HSF may recognize its binding site through the dyad symmetry of sites 3 and 4 but requires an adjacent site for stable interaction. Our data demonstrate that mHSF1 and mHSF2 bind specifically to the HSE through major groove interactions. Methidiumpropyl-EDTA footprinting revealed structural differences in the first and third repeats of the HSE, suggesting that the DNA is distorted in this region. The possibility that the HSE region is naturally distorted may assist in understanding how a trimer of HSF can bind to what is essentially an inverted repeat binding site. PMID- 8497257 TI - Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb mediated growth suppression. AB - Studies of naturally occurring mutations of the RB1 tumor suppressor gene have indicated that the E1A/T antigen-binding domain is important for pRb function. Mutations engineered within the C-terminal 135 amino acids of pRb also abrogate its growth-suppressive function during the G1 interval of the cell cycle. Both the pRb E1A/T antigen-binding domain and the C-terminal domain are required for interaction with the E2F transcription factor. A series of mutated pRb proteins has been used to define the C-terminal sequences which determine E2F binding, adenovirus E2 promoter inhibition, and negative growth control. Deletion of the C terminus to residue 870 allowed full pRb function, while further deletion to residue 841 inactivated pRb in each assay. Amino acid sequences immediately C terminal to the E1A/T antigen-binding domain were absolutely required for pRb activity. Mutations which prevented pRb from interacting with E2F also eliminated pRb-mediated E2 promoter repression and inactivated the ability of pRb to suppress cell growth. PMID- 8497258 TI - Purification of early-B-cell factor and characterization of its DNA-binding specificity. AB - Early-B-cell factor (EBF) is a nuclear protein that recognizes a functionally important sequence in the promoter of the mb-1 gene. Like the mb-1 gene, which encodes an immunoglobulin-associated protein, EBF is specifically expressed in the early stages of B-lymphocyte differentiation. We purified EBF by sequence specific DNA affinity chromatography and examined its biochemical properties and DNA-binding specificity. Crude nuclear extract and affinity-purified EBF generated protein-DNA complexes with the mb-1 promoter that were indistinguishable in electrophoretic mobility shift and DNase I footprint assays. Fractionation of affinity-purified EBF by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renaturation of isolated polypeptides indicated that EBF DNA-binding activity could be reconstituted from polypeptides with molecular masses of 62 to 65 kDa. Gel filtration chromatography suggested that native EBF has a molecular mass of 140 kDa, if a globular shape of the protein is assumed. Thus, EBF appears to be a dimer with subunits of 62 to 65 kDa. To characterize the DNA-binding specificity of purified EBF, we performed two sets of experiments. First, we examined various mutant EBF-binding sites for interaction with purified EBF in an electrophoretic mobility shift assay. Second, we used oligonucleotides containing pairs of randomized bases in a binding-site selection and amplification experiments to determine a preferred sequence for DNA binding by EBF. Taken together, the results of these experiments indicated that EBF recognizes variations on the palindromic sequence 5'-ATTCCCNNGGGAAT, with an optimal spacer of 2 bp between the half-sites. PMID- 8497259 TI - TAP1, a yeast gene that activates the expression of a tRNA gene with a defective internal promoter. AB - We developed a genetic selection system based on nonsense suppression in Saccharomyces cerevisiae to identify mutations in proteins involved in transcription initiation by RNA polymerase III. A SUP4 tRNA(Tyr) internal promoter mutation (A53T61) that was unable to suppress ochre mutations in vivo and was incapable of binding TFIIIC in vitro was used as the target for selection of trans-acting compensatory mutations. We identified two such mutations in the same gene, which we named TAP1 (for transcription activation protein). The level of the SUP4A53T61 transcript was threefold higher in the tap1-1 mutant than in the wild type. The tap1-1 mutant strain was also temperature sensitive for growth. The thermosensitive character cosegregated with the restorer of suppression activity, as shown by meiotic linkage analysis and coreversion of the two traits. At 1 to 2 h after a shift to the restrictive temperature, RNA synthesis was strongly inhibited in the tap1-1 mutant, preceding any effect upon protein synthesis or growth. A marked decrease in tRNA and 5S rRNA synthesis was seen, and shortly after that, rRNA synthesis was inhibited. By complementation of the ts- growth defect, we cloned the wild-type TAP1 gene. It is essential for yeast growth. We show in the accompanying report (T. L. Aldrich, G. Di Segni, B. L. McConaughy, N. J. Keen, S. Whelen, and B. D. Hall, Mol. Cell. Biol. 13:3434 3444, 1993) that TAP1 is identical to RAT1, a yeast gene implicated in poly(A)+ RNA export and that the TAP1/RAT1 gene product has extensive sequence similarity to the protein encoded by another yeast gene (variously named DST2, KEM1, RAR5, SEP1, or XRN1) having exonuclease and DNA strand transfer activity (reviewed by Kearsey and Kipling [Trends Cell Biol. 1:110-112, 1991]). PMID- 8497260 TI - Structure of the yeast TAP1 protein: dependence of transcription activation on the DNA context of the target gene. AB - Sequence data are presented for the Saccharomyces cerevisiae TAP1 gene and for a mutant allele, tap1-1, that activates transcription of the promoter-defective yeast SUP4 tRNA(Tyr) allele SUP4A53T61. The degree of in vivo activation of this allele by tap1-1 is strongly affected by the nature of the flanking DNA sequences at 5'-flanking DNA sequences as far away as 413 bp from the tRNA gene and by 3' flanking sequences as well. We considered the possibility that this dependency is related to the nature of the chromatin assembled on these different flanking sequences. TAP1 encodes a protein 1,006 amino acids long. The tap1-1 mutation consists of a thymine-to-cytosine DNA change that changes amino acid 683 from tyrosine to histidine. Recently, Amberg et al. reported the cloning and sequencing of RAT1, a yeast gene identical to TAP1, by complementation of a mutant defect in poly(A) RNA export from the nucleus to the cytoplasm (D. C. Amberg, A. L. Goldstein, and C. N. Cole, Genes Dev. 6:1173-1189, 1992). The RAT1/TAP1 gene product has extensive sequence similarity to a yeast DNA strand transfer protein that is also a riboexonuclease (variously known as KEM1, XRN1, SEP1, DST2, or RAR5; reviewed by Kearsey and Kipling [Trends Cell Biol. 1:110 112, 1991]). The tap1-1 amino acid substitution affects a region of the protein in which KEM1 and TAP1 are highly similar in sequence. PMID- 8497261 TI - Rapid changes in Drosophila transcription after an instantaneous heat shock. AB - Heat shock rapidly activates expression of some genes and represses others. The kinetics of changes in RNA polymerase distribution on heat shock-modulated genes provides a framework for evaluating the mechanisms of activation and repression of transcription. Here, using two methods, we examined the changes in RNA polymerase II association on a set of Drosophila genes at 30-s intervals following an instantaneous heat shock. In the first method, Drosophila Schneider line 2 cells were quickly frozen to halt transcription, and polymerase distribution was analyzed by a nuclear run-on assay. RNA polymerase transcription at the 5' end of the hsp70 gene could be detected within 30 to 60 s of induction, and by 120 s the first wave of polymerase could already be detected near the 3' end of the gene. A similar rapid induction was found for the small heat shock genes (hsp22, hsp23, hsp26, and hsp27). In contrast to this rapid activation, transcription of the histone H1 gene was found to be rapidly repressed, with transcription reduced by approximately 90% within 300 s of heat shock. Similar results were obtained by an in vivo UV cross-linking assay. In this second method, cell samples removed at 30-s intervals were irradiated with 40 microseconds bursts of UV light from a Xenon flash lamp, and the distribution of polymerase was examined by precipitating UV cross-linked protein-DNA complexes with an antibody to RNA polymerase II. Both approaches also showed the in vivo rate of movement of the first wave of RNA polymerase through the hsp70 gene to be approximately 1.2 kb/min. PMID- 8497262 TI - V(D)J recombination in mammalian cell mutants defective in DNA double-strand break repair. AB - V(D)J recombination has been examined in several X-ray-sensitive and double strand break repair-deficient Chinese hamster cell mutants. Signal joint formation was affected in four mutants (xrs 5, XR-1, V-3, and XR-V9B cells, representing complementation groups 1 through 4, respectively) defective in DNA double-strand break rejoining. Among these four, V-3 and XR-V9B were the most severely affected. Only in V-3 was coding joint formation also affected. Ataxia telangiectasia-like hamster cell mutants (V-E5 and V-G8), which are normal for double-strand break repair but are X ray sensitive, were normal for all aspects of the V(D)J recombination reaction, indicating that X-ray sensitivity is not the common denominator but that the deficiency in double-strand break repair appears to be. The abnormality at the signal joints consisted of an elevated incidence of nucleotide loss from each of the two signal ends. Interestingly, in complementation groups 1 (xrs 5) and 2 (XR-1), signal joint formation was within the normal range under some transfection conditions. This suggests that the affected gene products in these two complementation groups are not catalytic components. Instead, they may be either secondary or stochiometric components involved in the later stages of both the V(D)J recombination reaction and double strand break repair. The fact that such factors can affect the precision of the signal joint has mechanistic implications for V(D)J recombination. PMID- 8497263 TI - Activation of Drosophila heat shock factor: conformational change associated with a monomer-to-trimer transition. AB - The induction of heat shock genes in eukaryotic cells is regulated by the transcription factor heat shock factor (HSF). Activation of HSF occurs at two independent levels, DNA binding and the acquisition of transcriptional competence. The binding of HSF to DNA is accomplished by a stress-induced oligomeric switch of HSF protein. We have defined the oligomeric state of the latent and induced forms of HSF by measuring the sedimentation coefficient and the Stokes radius of the protein in Drosophila cell extracts. Calculation of the native molecular mass indicates that the two forms of Drosophila HSF are best described as a monomer and trimer, respectively, of the 77-kDa HSF polypeptide. The monomeric and trimeric states of HSF were verified by chemical cross-linking experiments. The finding of a monomeric composition for the latent form of HSF is incompatible with speculative models which suggest that molecular chaperones such as hsp70 feed back to inhibit trimerization of HSF by forming a stable heteromeric complex. We also found that both HSF monomers and HSF trimers exhibit unusually high frictional ratios, indicating that they have asymmetric shapes. The degree of asymmetry is significantly greater for the HSF trimer, suggesting that the monomer undergoes a conformational change to a more extended structure upon trimerization. These findings are consistent with a model for the inert HSF protein that is based on a monomer constrained by intramolecular coiled-coil interactions between amino- and carboxy-terminal domains. PMID- 8497264 TI - Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. AB - We have investigated the RNA binding specificity of Hel-N1, a human neuron specific RNA-binding protein, which contains three RNA recognition motifs. Hel-N1 is a human homolog of Drosophila melanogaster elav, which plays a vital role in the development of neurons. A random RNA selection procedure revealed that Hel-N1 prefers to bind RNAs containing short stretches of uridylates similar to those found in the 3' untranslated regions (3' UTRs) of oncoprotein and cytokine mRNAs such as c-myc, c-fos, and granulocyte macrophage colony-stimulating factor. Direct binding studies demonstrated that Hel-N1 bound and formed multimers with c myc 3' UTR mRNA and required, as a minimum, a specific 29-nucleotide stretch containing AUUUG, AUUUA, and GUUUUU. Deletion analysis demonstrated that a fragment of Hel-N1 containing 87 amino acids, encompassing the third RNA recognition motif, forms an RNA binding domain for the c-myc 3' UTR. In addition, Hel-N1 was shown to be reactive with autoantibodies from patients with paraneoplastic encephalomyelitis both before and after binding to c-myc mRNA. PMID- 8497265 TI - Only the DNA binding and transactivation domains of c-Myb are required to block terminal differentiation of murine erythroleukemia cells. AB - The c-Myb protein is a transcription factor with an apparent but poorly defined role in hematopoietic cell growth and differentiation. The DNA binding and several transcriptional regulatory domains of the c-Myb protein have been defined by transient transfections into nonhematopoietic cell lines. Although the relationship between these domains and transformation has been studied, little is known about the function of these domains during hematopoietic maturation. Up regulation of stably transfected c-myb in murine erythroleukemia (MEL) cells blocks terminal differentiation when MEL cells are induced to differentiate with N,N'-hexamethylene bisacetamide. To determine which functional domains of c-Myb are necessary and sufficient to block differentiation, mutated c-myb constructs under the control of a murine metallothionein promoter were transfected into C19 MEL cells, and stable clonal cell lines were established. The ability of Myb mutants to block differentiation paralleled their ability to transactivate transcription of a reporter gene containing Myb-responsive elements, by transient transfection into a lymphoid cell line. The smallest c-Myb mutant able to block differentiation consisted of the DNA binding domain juxtaposed to the transactivation domain. Therefore, the DNA binding domain and the transactivation domain are necessary and sufficient for c-Myb to block differentiation in MEL cells. PMID- 8497266 TI - Regulation of the proneural gene achaete by helix-loop-helix proteins. AB - The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo. PMID- 8497267 TI - E2A and E2-2 are subunits of B-cell-specific E2-box DNA-binding proteins. AB - A class of helix-loop-helix (HLH) proteins, including E2A (E12 and E47), E2-2, and HEB, that bind in vitro to DNA sequences present in the immunoglobulin (Ig) enhancers has recently been identified. E12, E47, E2-2, and HEB are each present in B cells. The presence of many different HLH proteins raises the question of which of the HLH proteins actually binds the Ig enhancer elements in B cells. Using monoclonal antibodies specific for both E2A and E2-2, we show that both E2 2 and E2A polypeptides are present in B-cell-specific Ig enhancer-binding complexes. E2-box-binding complexes in pre-B cells contain both E2-2 and E2A HLH subunits, whereas in mature B cells only E2A gene products are present. We show that the difference in E2-box-binding complexes in pre-B and mature B cells may be caused by differential expression of E2A and E2-2. PMID- 8497268 TI - The octamer/mu E4 region of the immunoglobulin heavy-chain enhancer mediates gene repression in myeloma x T-lymphoma hybrids. AB - We have shown previously that the immunoglobulin heavy-chain enhancer acts as a repressor of gene transcription in hybrids between immunoglobulin-producing myelomas and a T-lymphoma line. We have now mapped this repressive activity to a 51-bp enhancer subfragment which contains the octamer and mu E4 protein-binding motifs. Even a single copy of this subfragment will repress gene expression in hybrid cells. Mutational analyses of the repressor fragment suggest that in non-B cells, a strong transcriptional repressor(s) functions through the same motifs important for gene activation in B cells. Changes in chromatin structure that accompany reporter gene repression suggest a general mechanism for prohibiting immunoglobulin heavy-chain locus activation in inappropriate cell types. PMID- 8497269 TI - GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is required for phosphorylation of eukaryotic translation initiation factor 2 by protein kinase GCN2. AB - Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) by the protein kinase GCN2 mediates increased translation of the transcriptional activator GCN4 in amino acid-starved yeast cells. We show that this key phosphorylation event and the attendant translational induction of GCN4 are dependent on the product of a previously uncharacterized gene, GCN1. Inactivation of GCN1 did not affect the level of eIF-2 alpha phosphorylation when mammalian eIF-2 alpha kinases were expressed in yeast cells in place of GCN2, arguing against an involvement of GCN1 in dephosphorylation of eIF-2 alpha. In addition, while GCN1 is required in vivo for phosphorylation of eIF-2 alpha by GCN2, cell extracts from gcn1 delta strains contained wild-type levels of GCN2 eIF-2 alpha-kinase activity. On the basis of these results, we propose that GCN1 is not needed for GCN2 kinase activity per se but is required for in vivo activation of GCN2 in response to the starvation signal, uncharged tRNA. GCN1 encodes a protein of 297 kDa with an 88-kDa region that is highly similar in sequence to translation elongation factor 3 identified in several fungal species. This sequence similarity raises the possibility that GCN1 interacts with ribosomes or tRNA molecules and functions in conjunction with GCN2 in monitoring uncharged tRNA levels during the process of translation elongation. PMID- 8497270 TI - The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation dependent manner. AB - The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappa B DNA motifs. Bcl 3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappa B (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined I kappa B, which maintains heterodimeric NF-kappa B p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, I kappa B related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52. PMID- 8497271 TI - Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. AB - Cyclins and proto-oncogenes including c-myc have been implicated in eukaryotic cell cycle control. The role of cyclins in steroidal regulation of cell proliferation is unknown, but a role for c-myc has been suggested. This study investigated the relationship between regulation of T-47D breast cancer cell cycle progression, particularly by steroids and their antagonists, and changes in the levels of expression of these genes. Sequential induction of cyclins D1 (early G1 phase), D3, E, A (late G1-early S phase), and B1 (G2 phase) was observed following insulin stimulation of cell cycle progression in serum-free medium. Transient acceleration of G1-phase cells by progestin was also accompanied by rapid induction of cyclin D1, apparent within 2 h. This early induction of cyclin D1 and the ability of delayed administration of antiprogestin to antagonize progestin-induced increases in both cyclin D1 mRNA and the proportion of cells in S phase support a central role for cyclin D1 in mediating the mitogenic response in T-47D cells. Compatible with this hypothesis, antiestrogen treatment reduced the expression of cyclin D1 approximately 8 h before changes in cell cycle phase distribution accompanying growth inhibition. In the absence of progestin, antiprogestin treatment inhibited T-47D cell cycle progression but in contrast did not decrease cyclin D1 expression. Thus, changes in cyclin D1 gene expression are often, but not invariably, associated with changes in the rate of T-47D breast cancer cell cycle progression. However, both antiestrogen and antiprogestin depleted c-myc mRNA by > 80% within 2 h. These data suggest the involvement of both cyclin D1 and c-myc in the steroidal control of breast cancer cell cycle progression. PMID- 8497272 TI - A GC-rich domain with bifunctional effects on mRNA and protein levels: implications for control of transforming growth factor beta 1 expression. AB - Chimeric plasmids containing selected reporter coding domains and portions of the transforming growth factor beta 1 (TGF-beta 1) 3' untranslated region (UTR) were prepared and used to identify potential mechanisms involved in regulating the biosynthesis of TGF-beta 1. Transient transfections with core and chimeric constructs containing the chloramphenicol acetyltransferase (CAT) reporter showed that steady-state CAT mRNA levels were decreased two- to threefold in response to the TGF-beta 1 3' UTR. Interestingly, CAT activity was somewhat increased in the same transfectants. Thus, production of CAT protein per unit of mRNA was stimulated by the TGF-beta 1 3' UTR (approximately fourfold in three cell lines of distinct lineage). The translation-stimulatory effect of the TGF-beta 1 3' UTR suggested by these studies in vivo was confirmed in vitro by cell-free translation of core and chimeric transcripts containing the growth hormone coding domain. These studies showed that production of growth hormone was stimulated threefold by the TGF-beta 1 3' UTR. A deletion analysis in vivo indicated that the GC-rich domain in the TGF-beta 1 3' UTR was responsible for both the decrease in mRNA levels and stimulation of CAT activity-mRNA. We conclude that this GC rich domain can have a bifunctional effect on overall protein expression. Moreover, the notable absence of this GC-rich domain in TGF-beta 2, TGF-beta 3, TGF-beta 4, and TGF-beta 5 indicates that expression of distinct TGF-beta family members can be differentially controlled in cells. PMID- 8497273 TI - NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3' alpha enhancer at early stages of B-cell differentiation. AB - We have identified a nuclear factor expressed in pro-B-, pre-B-, and B-cell lines that binds to two sites within the murine immunoglobulin heavy-chain (IgH) 3' alpha enhancer (3' alpha E). These sites were defined by oligonucleotide competition in an electrophoretic mobility shift assay (EMSA) and methylation interference footprinting. The 3' alpha E-binding factor is indistinguishable from NF-HB (B-lineage-specific nuclear factor that binds to the IgH gene) and the B-lineage-specific transcription factor BSAP by several criteria, including similar cell type distribution of binding activity, cross-competition of binding sites in EMSA, similar protein size as demonstrated by UV cross-linking, and sequence identity of one of the 3' alpha E-binding sites with a BSAP-binding site within the promoter of the sea urchin late histone gene H2A-2.2. These observations indicate that 3' alpha E is one of the mammalian targets for NF-HB (BSAP). Transient-transfection assays with chloramphenicol acetyltransferase gene constructs containing 3' alpha E and mutant 3' alpha E, in which one of the NF-HB binding sites was inactivated by site-specific mutagenesis, showed ca. five- to sixfold-enhanced activity of mutated 3' alpha E over parental 3' alpha E in B cell lines (NF-HB+), while no significant difference was observed in plasmacytoma cells (NF-HB-). We conclude from these observations that NF-HB (BSAP) acts as a repressor of the mouse IgH 3' alpha E. PMID- 8497274 TI - Overproduction of v-Myc in the nucleus and its excess over Max are not required for avian fibroblast transformation. AB - The cellular proto-oncogene c-myc can acquire transforming potential by a number of different means, including retroviral transduction. The transduced allele generally contains point mutations relative to c-myc and is overexpressed in infected cells, usually as a v-Gag-Myc fusion protein. Upon synthesis, v-Gag-Myc enters the nucleus, forms complexes with its heterodimeric partner Max, and in this complex binds to DNA in a sequence-specific manner. To delineate the role for each of these events in fibroblast transformation, we introduced several mutations into the myc gene of the avian retrovirus MC29. We observed that Gag Myc with a mutated nuclear localization signal is confined predominantly in the cytoplasm and only about 5% of the protein could be detected in the nucleus (less than the amount of endogenous c-Myc). Consequently, only a small fraction of Max is associated with Myc. However, cells infected with this mutant exhibit a completely transformed phenotype in vitro, suggesting that production of enough v Gag-Myc to tie up all cellular Max is not needed for transformation. While the nuclear localization signal is dispensable for transformation, minimal changes in the v-Gag-Myc DNA-binding domain completely abolish its transforming potential, consistent with a role of Myc as a transcriptional regulator. One of its potential targets might be the endogenous c-myc, which is repressed in wild-type MC29-infected cells. Our experiments with MC29 mutants demonstrate that c-myc down-regulation depends on the integrity of the v-Myc DNA-binding domain and occurs at the RNA level. Hence, it is conceivable that v-Gag-Myc, either directly or circuitously, regulates c-myc transcription. PMID- 8497275 TI - Isolation of STD1, a high-copy-number suppressor of a dominant negative mutation in the yeast TATA-binding protein. AB - The TATA-binding protein (TBP) is an essential component of the transcriptional machinery of all three nuclear RNA polymerase enzymes. Comparison of the amino acid sequence of TBPs from a number of species reveals a highly conserved 180 residue C-terminal domain. In contrast, the N terminus is variable in both size and amino acid sequence. Overexpression of a TBP protein with a deletion of the nonconserved N terminus (TBP delta 57) in Saccharomyces cerevisiae results in a dominant negative phenotype of extremely slow growth. Associated with the slow growth phenotype are defects in RNA polymerase II transcription in vivo. We have screened a high-copy-number yeast genomic library for suppression of the slow growth phenotype and have isolated plasmids which encode suppressors of TBP delta 57 overexpression. Here we report the sequence and initial characterization of one suppressor, designated STD1 for suppressor of TBP deletion. The STD1 gene contains a single continuous open reading frame with the potential to encode a 50.2-kDa protein. Disruption of the STD1 gene indicates that it is not essential for vegetative growth, mating, or sporulation. High-copy-number suppression by the STD1 gene is not the result of a decrease in TBP delta 57 protein accumulation or DNA-binding activity; instead, STD1 suppression is coincident with the elimination of TBP delta 57-induced RNA polymerase II defects in both uninduced and induced transcription in vivo. PMID- 8497276 TI - Negative regulation of immunoglobulin kappa light-chain gene transcription by a short sequence homologous to the murine B1 repetitive element. AB - B-cell-specific expression of the immunoglobulin kappa light-chain (Ig kappa) gene is in part accomplished by negative regulatory influences. Here we describe a new negatively acting element (termed kappa NE) immediately upstream of the NF kappa B-binding site in the Ig kappa intronic enhancer. The 27-bp kappa NE sequence is conserved in the corresponding positions in the rabbit and human Ig kappa genes, and the human kappa NE homolog was shown to have a similar negative regulatory activity. Data base searches using the mouse kappa NE sequence revealed a striking homology to murine B1 repetitive sequences. A sequence homologous to kappa NE and B1 was also noted in a previously identified silencer element in the murine T-cell receptor alpha locus. The homologous T-cell receptor alpha locus sequence, but notably not a corresponding 27-bp B1 consensus sequence, showed a negative regulatory potential similar to that of kappa NE. The negative effect of kappa NE by itself was not cell type specific but became so when paired with its 5'-flanking sequence in the Ig kappa enhancer. A short (30 bp) fragment upstream of kappa NE (termed kappa BS) was found to be necessary and sufficient for abolishing the negative effect of kappa NE in B cells. Point mutations in a T-rich motif within the kappa BS sequence allowed the transcriptional repression by kappa NE to be evident in B cells as well as other cells. As suggested by this cell-independent negative activity, proteins binding to the mouse and human kappa NE sequences were identified in all cell types tested. PMID- 8497277 TI - Disruption of largest subunit RNA polymerase II genes in Trypanosoma brucei. AB - Two types of largest subunit RNA polymerase II (pol II) genes (pol IIA and pol IIB), differing in 3 amino acid substitutions, are encoded in the Trypanosoma brucei (stock 427-60) genome. As a result, the alpha-amanitin-resistant transcription of the procyclic acidic repetitive protein (PARP) and variant surface glycoprotein (VSG) genes was proposed to involve a modified, alpha amanitin-resistant form of the largest subunit of pol II. Alternatively, pol I could transcribe the PARP and VSG genes. To discriminate between these two models, we deleted the N-terminal domain (about one-third of the polypeptide), which encodes the amino acid substitutions which discriminated the pol IIA and pol IIB genes, at both pol IIB alleles. The pol IIB- trypanosomes still transcribe the PARP genes and the VSG gene promoter region in insect-form trypanosomes by alpha-amanitin-resistant RNA polymerases, while control housekeeping genes are transcribed in an alpha-amanitin-sensitive manner, presumably by pol IIA. We conclude that the alpha-amanitin-resistant transcription of protein coding genes in T. brucei is not mediated by a diverged form of the largest subunit of pol II and that the presence of both the pol IIA and pol IIB genes is not essential for trypanosome viability. This conclusion was further supported by the finding that individual trypanosome variants exhibited allelic heterogeneity for the previously identified amino acid substitutions and that various permutations of the polymorphic amino acids generate at least four different types of largest subunit pol II genes. The expression of the PARP genes and the VSG gene promoter region by alpha-amanitin-resistant RNA polymerases in the pol IIB- trypanosomes provides evidence for transcription of these genes by pol I. PMID- 8497278 TI - Functional domains of the yeast STE12 protein, a pheromone-responsive transcriptional activator. AB - The pheromone response pathway of the yeast Saccharomyces cerevisiae is necessary for the basal level of transcription of cell-type-specific genes, as well as the induced level observed after pheromone treatment. The STE12 protein binds to the DNA sequence designated the pheromone response element and is a target of the pheromone-induced signal. We generated 6-nucleotide linker insertion mutants, internal-deletion mutants, and carboxy-terminal truncation mutants of STE12 and assayed them for their ability to restore mating and transcriptional activity to a ste12 delta strain. Two of these mutant proteins retain the capacity to mediate basal transcription but show little or no induced transcription upon pheromone treatment. Cells producing these proteins cannot mate, formally demonstrating that the ability to respond to pheromone by increasing gene expression is essential for the mating process. Since distinct domains of STE12 appear to be required for basal versus induced transcription, we suggest that the pheromone induced signal is likely to target residues of the protein different from those targeted by the basal signal because of the constitutive activity of the response pathway. Our analysis of mutant STE12 proteins also indicates that only the DNA binding domain is sensitive to the small changes caused by the linker insertions. In addition, we show that, while the carboxy-terminal sequences necessary for STE12 to form a complex with the transcription factor MCM1 are not essential for mating, these sequences are required for optimal transcriptional activity. PMID- 8497279 TI - Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro. AB - Several regulatory interactions between the AP-1 and the nuclear hormone receptor families of transcription factors have been reported. However, the molecular mechanisms that underlie these interactions remain unknown, and models derived from transient-transfection experiments are contradictory. We have investigated the effect of the purified glucocorticoid receptor (GR) DNA-binding domain (GR residues 440 to 533 [GR440-533]) on DNA binding and transcription activation by Fos-Jun heterodimers and Jun homodimers. GR440-533 differentially inhibited DNA binding and transcription activation by Fos-Jun heterodimers. Inhibition of Jun homodimers required a 10-fold-higher concentration of GR440-533. An excess of Fos monomers protected Fos-Jun heterodimers from inhibition by GR440-533. Surprisingly, regions outside the leucine zipper and basic region were required for GR inhibition of Fos and Jun DNA binding. The region of GR440-533 required for inhibition of Fos-Jun DNA binding was localized to the zinc finger DNA binding domain. However, inhibition of Fos-Jun DNA binding was independent of DNA binding by GR440-533. GR440-533 also differentially inhibited Fos-Jun heterodimer binding to the proliferin plfG element. Differential inhibition of DNA binding by different AP-1 family complexes provides a potential mechanism for the diverse interactions between nuclear hormone receptors and AP-1 family proteins at different promoters and in different cell types. PMID- 8497280 TI - Multiple SWI6-dependent cis-acting elements control SWI4 transcription through the cell cycle. AB - The Saccharomyces cerevisiae SWI4 gene encodes an essential transcription factor which controls gene expression at the G1/S transition of the cell cycle. SWI4 transcription itself is cell cycle regulated, and this periodicity is crucial for the normal cell cycle regulation of HO and at least two of the G1 cyclins. Since the regulation of SWI4 is required for normal cell cycle progression, we have characterized cis- and trans-acting regulators of SWI4 transcription. Deletion analysis of the SWI4 promoter has defined a 140-bp region which is absolutely required for transcription and can function as a cell cycle-regulated upstream activating sequence (UAS). The SWI4 UAS contains three potential MluI cell cycle boxes (MCBs), which are known cell cycle-regulated promoter elements. Deletion of all three MCBs in the SWI4 UAS decreases the level of SWI4 mRNA 10-fold in asynchronous cultures but does not abolish periodicity. These data suggest that MCBs are involved in SWI4 UAS activity, but at least one other periodically regulated element must be present. Since SWI6 is known to bind to MCBs and regulate their activity, the role of SWI6 in SWI4 expression was analyzed. Although the MCBs cannot account for the full cell cycle regulation of SWI4, mutations in SWI6 eliminate the normal periodicity of SWI4 transcription. This suggests that the novel cell cycle-regulated element within the SWI4 promoter is also SWI6 dependent. The constitutive transcription of SWI4 in SWI6 mutant cells occurs at an intermediate level, which indicates that SWI6 is required for the full activation and repression of SWI4 transcription through the cell cycle. It also suggests that there is another pathway which can activate SWI4 transcription in the absence of SWI6. The second activator may also target MCB elements, since SWI4 transcription drops dramatically when they are deleted. PMID- 8497281 TI - Evidence for differential functions of the p50 and p65 subunits of NF-kappa B with a cell adhesion model. AB - The p50 and p65 subunits of NF-kappa B represent two members of a gene family that shares considerable homology to the rel oncogene. Proteins encoded by these genes form homo- and heterodimers which recognize a common DNA sequence motif. Recent data have suggested that homodimers of individual subunits of NF-kappa B can selectively activate gene expression in vitro. To explore this possibility in a more physiological manner, murine embryonic stem (ES) cells were treated with phosphorothio antisense oligonucleotides to either p50 or p65. Within 5 h after exposure to phosphorothio antisense p65 oligonucleotides, cells exhibited dramatic alterations in adhesion properties. Similar findings were obtained in a stable cell line that expressed a dexamethasone-inducible antisense mRNA to p65. Although antisense oligonucleotides raised against both p50 and p65 elicited a significant reduction in their respective mRNAs, only the cells treated with antisense p50 maintained a normal morphology. However, 6 days following removal of leukemia-inhibiting factor, a growth factor which suppresses embryonic stem cell differentiation, adhesion properties of cells treated with the antisense p50 oligonucleotides were markedly affected. The ability of the individual antisense oligonucleotides to elicit differential effects on cell adhesion, a property dependent upon the stage of differentiation, suggests that the p50 and p65 subunits of NF-kappa B regulate gene expression either as homodimers or as heterodimers with other rel family members. Furthermore, the finding that reduction in p65 expression alone had profound effects on cell adhesion properties indicates that p65 plays an important role in nonstimulated cells and cannot exist solely complexed with the cytosolic inhibitory protein I kappa B. PMID- 8497282 TI - Antisense rescue defines specialized and generalized functional domains for c-Fos protein. AB - Serum induces the expression of a number of proteins with similar transcriptional properties, including those encoded by the proto-oncogenes c-fos and c-jun. This study employs a novel antisense rescue method to determine whether antisense resistant genes (constructed by deletion of antisense RNA target sequences) can replace c-fos expression during serum-induced DNA synthesis. Immunoprecipitation studies and nuclease protection assays demonstrated that anti-fos RNA inhibited endogenous c-fos expression but did not inhibit expression of transfected antisense-resistant mutant c-fos genes. The results of nuclear-labelling and cellular-proliferation studies indicated that C terminally truncated Fos mutants, including FBR v-fos, could not rescue endogenous Fos, although full-length and minimally truncated c-fos expression vectors could restore serum-induced DNA synthesis in cells expressing anti-fos RNA. Overexpression of c-Jun protein (Jun) could not restore serum-induced DNA synthesis to cells expressing inducible anti fos RNA despite equivalent transactivation of an AP-1 target gene. Thus, the antisense rescue method defines a specialized function for c-Fos protein which is distinct from the function(s) of Jun and/or transforming FBR v-Fos proteins. PMID- 8497283 TI - Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. AB - BACKGROUND: Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension. METHODS: We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3. RESULTS: In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension. CONCLUSIONS: Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder. PMID- 8497284 TI - Efficacy of aerosolized tobramycin in patients with cystic fibrosis. AB - BACKGROUND: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa. PMID- 8497285 TI - Brief report: autoimmune protein S deficiency in a boy with severe thromboembolic disease. PMID- 8497286 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-1993. A 56-year-old woman with virilization. PMID- 8497287 TI - How much will health care reform cost? PMID- 8497288 TI - What we learn from infants with brain tumors. PMID- 8497289 TI - Is steroid-induced osteoporosis preventable? PMID- 8497290 TI - Head and neck cancer. PMID- 8497291 TI - Head and neck cancer. PMID- 8497292 TI - Smoking and radiation therapy for head and neck cancer. PMID- 8497293 TI - HIV-related thrombocytopenia. PMID- 8497294 TI - Cochlear implants. PMID- 8497295 TI - Cochlear implants. PMID- 8497296 TI - Cochlear implants. PMID- 8497297 TI - The American Health Care System--Medicare. PMID- 8497298 TI - The American Health Care System--Medicare. PMID- 8497299 TI - The American Health Care System--Medicare. PMID- 8497300 TI - The American Health Care System--Medicare. PMID- 8497301 TI - Clinical problem-solving: diagnosis by drug reaction. PMID- 8497302 TI - Clinical problem-solving: diagnosis by drug reaction. PMID- 8497303 TI - Delaney must go. PMID- 8497304 TI - OTA tackles gene patents. PMID- 8497305 TI - Dispute over money may foil US AIDS vaccines trial. PMID- 8497306 TI - India moves ahead cautiously on US AIDS project. PMID- 8497307 TI - Drawbacks of peer review. PMID- 8497308 TI - Visual perception. Seeing the tree for the woods. PMID- 8497309 TI - Cell cycle. Sunburnt fission yeast. PMID- 8497310 TI - Developmental biology. On the other hand ... PMID- 8497311 TI - Messenger RNA. Springtime in the desert. PMID- 8497312 TI - Bateson and peacocks' tails. PMID- 8497313 TI - Bateson and peacocks' tails. PMID- 8497314 TI - Why microtubules grow and shrink. PMID- 8497315 TI - Pleckstrin domain homology. PMID- 8497316 TI - Voltage-sensitive magnetic gels as magnetic resonance monitoring agents. AB - Many polymer gels undergo a volume phase transition in electric fields. We report here the synthesis of a polyelectrolyte gel that incorporates magnetic particles of iron oxide into the polymer network; these particles couple the gel volume transition to the NMR relaxation times of the surrounding water. We find that the water proton relaxation rates (T2(-1)) in aqueous suspensions of particles of the magnetic gel increase significantly in an electric field. Such changes can also be induced by the hyperpolarization of red blood cells in the suspension, presumably as a result of the electric fields at the cell membrane surfaces. These gels may play a part in magnetic resonance imaging analogous to that of voltage-sensitive dyes in optical imaging. PMID- 8497317 TI - A neural basis for visual search in inferior temporal cortex. AB - We often search for a face in a crowd or for a particular object in a cluttered environment. In this type of visual search, memory interacts with attention: the mediating neural mechanisms should include a stored representation of the object and a means for selecting that object from among others in the scene. Here we test whether neurons in inferior temporal cortex, an area known to be important for high-level visual processing, might provide these components. Monkeys were presented with a complex picture (the cue) to hold in memory during a delay period. The cue initiated activity that persisted through the delay among the neurons that were tuned to its features. The monkeys were then given 2-5 choice pictures and were required to make an eye movement to the one (the target) that matched the cue. About 90-120 milliseconds before the onset of the eye movement to the target, responses to non-targets were suppressed and the neuronal response was dominated by the target. The results suggest that inferior temporal cortex is involved in selecting the objects to which we attend and foveate. PMID- 8497318 TI - Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. AB - The neurotrophins are a family of neurotrophic factors that promote survival and differentiation of various neuronal populations. Although the long-term effects of neurotrophins on neuronal survival and differentiation have been intensively studied, nothing is known about their effects on synaptic function. Here we report that acute exposure to neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF), but not nerve growth factor (NGF), rapidly potentiates the spontaneous and impulse-evoked synaptic activity of developing neuromuscular synapses in culture. The effect appears to be presynaptic in origin and to be mediated by the Trk family of receptor tyrosine kinases. These results provide evidence for the regulation of the function of developing synapses by neurotrophins. PMID- 8497319 TI - In utero rearrangements in the trithorax-related oncogene in infant leukaemias. AB - The majority (approximately 75%) of infant acute leukaemias have a reciprocal translocation between chromosome 11q23 and one of several partner chromosomes. The gene at 11q23 (named MLL, ALL-1, HRX or HTRX-1; refs 2-6) has been cloned and shares homology with the Drosophila developmental gene trithorax. Rearrangements of this gene (called HRX here) occur in introns and cluster in a region of approximately 10 kb; individual patients have different breakpoints. Here we describe three pairs of infant twins with concordant leukaemia who each share unique (clonal) but non-constitutive HRX rearrangements in their leukaemic cells, providing evidence that the leukaemogenic event originates in utero and unequivocal support for the intra-placental 'metastasis' hypothesis for leukaemia concordance in twins. PMID- 8497320 TI - Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. AB - Leukaemia inhibitory factor (LIF) has a variety of effects on different cell types in vitro, inhibiting the differentiation of embryonic stem cells and promoting the survival and/or proliferation of primitive haematopoietic precursors and primordial germ cells. Here we show that LIF-deficient mice derived by gene targeting techniques have dramatically decreased numbers of stem cells in spleen and bone marrow. Injection of spleen and marrow cells from these mice promotes long-term survival of lethally irradiated wild-type animals, however, showing that the LIF- stem cells remain pluripotent. The numbers of committed progenitors are also reduced in the spleen but not the bone marrow, suggesting that stem cells interact differently with the splenic and medullary microenvironment. Heterozygous animals are intermediate in phenotype, implying that LIF has a dosage effect, and defects in stem cell number can be compensated by exogenous LIF. LIF thus appears to be required for the survival of the normal pool of stem cells, but not their terminal differentiation. PMID- 8497321 TI - A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42. AB - The Ras-related Rho subfamily of GTP-binding proteins (p21s), which includes Rho, Rac and Cdc42Hs, is implicated in different aspects of cytoskeletal organization. These proteins behave like Ras (p21ras) in that their active GTP-bound form is inactivated by intrinsic hydrolysis of the nucleotide gamma-phosphate, which can be stimulated by GTPase-activating proteins (GAPs). We have previously shown that there is a diversity of GAPs that recognize this subfamily, including n chimaerin, which is enriched in the hippocampus; we also detected proteins that bind these p21 proteins and seem to inhibit GTP hydrolysis. We now report the characterization of a hippocampal complementary DNA encoding a tyrosine kinase that specifically binds Cdc42Hs in its GTP-bound form. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain and inhibits both the intrinsic and GAP-stimulated GTPase activity of Cdc42Hs. Our findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway. PMID- 8497322 TI - Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2. AB - The dependence of cell-cycle progression on the integrity of the genome has been described as checkpoint control. A number of mutants of the fission yeast Schizosaccharomyces pombe, selected for their sensitivity to DNA damage caused by radiation (rad mutants) or to the DNA synthesis inhibitor hydroxyurea (hus mutants) have been classified as checkpoint mutants because they fail to arrest the cell cycle in response to DNA damage or incompletely replicated DNA. Coupling of the checkpoint pathways that monitor DNA repair and replication to control of the cell cycle is essential. In a search for components that interact with the cell-cycle regulatory kinase p34cdc2, we have identified a novel fission yeast protein kinase homologue which is involved in cell-cycle arrest when DNA damage has occurred or when unligated DNA is present. We have called the gene encoding this protein chk1 for checkpoint kinase. Multiple copies of chk1 partially rescue the ultraviolet sensitivity of rad1-1, a mutant deficient in checkpoint control. Identification of a gene involved in checkpoint control as a rescue of a cdc2 mutant links the rad1-dependent DNA-damage-sensing pathway and p34cdc2 activity. PMID- 8497323 TI - Phosphorylation of C-terminal domain of RNA polymerase II is not required in basal transcription. AB - Phosphorylation of the heptapeptide repeats in the C-terminal domain (CTD) of the largest subunit of RNA polymerase II has been widely proposed as an essential step in transcription initiation on the basis of findings indicating (1) that the CTDs of RNA polymerase II molecules actively engaged in transcription are highly phosphorylated; (2) that polymerase molecules containing non-phosphorylated CTDs preferentially enter the preinitiation complex where they are subsequently phosphorylated; and (3) that essential initiation factors b from yeast, delta from rat, and BTF2(TFIIH) from human cells have closely associated CTD-kinase activities. Here we take advantage of a highly purified enzyme system which supports both CTD phosphorylation and basal transcription to test this hypothesis directly. Using the isoquinoline sulphonamide derivative H-8, which is a potent inhibitor of CTD kinase, we show that basal transcription occurs in the absence of CTD phosphorylation. PMID- 8497324 TI - TBASE: a computerized database for transgenic animals and targeted mutations. AB - A computerized database, called TBASE, has been developed to organize and make available information on transgenic animals and targeted mutations by using resources at the Oak Ridge National Laboratory (ORNL) and Johns Hopkins University (JHU). The database is available through the JHU Computational Biology Gopher Server. To ensure that all interested users have access, several mechanisms will be installed to accommodate varying levels of telecommunication network connectivity. PMID- 8497325 TI - [Remember hereditary metabolic diseases in children in which no satisfactory diagnosis can be established]. PMID- 8497326 TI - [Prader-Willi syndrome and drowsiness; diagnostic attentiveness advised]. PMID- 8497327 TI - [Myth about the disadvantage of decreasing serum cholesterol refuted]. PMID- 8497328 TI - [Thoracoscopic surgery: advancing carefully]. PMID- 8497329 TI - [Langerhans cell histiocytosis]. PMID- 8497330 TI - [Langerhans-cell histiocytosis (histiocytosis X); 20-year experience in the Emma Kinderziekenhuis, 1969-1988]. AB - PURPOSE: Evaluation of the diagnostic and therapeutic results in 50 paediatric patients treated for Langerhans cell histiocytosis (LCH) over a 20-year period at the Emma Kinderziekenhuis (EKZ) in Amsterdam. PATIENTS AND METHODS: Group A consisted of 18 patients with localized disease affecting the bone or the skin. Twenty-four patients had multifocal disease (group B) affecting more than one bone or soft-tissue lesions with or without skin lesions, diabetes insipidus or both. Eight patients (group C) had multifocal disease with evidence of dysfunction of liver and/or lungs and/or haemopoietic system. Treatment consisted of one or more of the following possibilities: curettage, radiotherapy, corticosteroids (locally, intralesional, orally) or chemotherapy. Some patients were simply observed. RESULTS: At present all patients of group A (100%) are in complete clinical remission and only two patients have developed sequelae. Twenty one patients of group B (88%) are in complete clinical remission. One patient died of an apudoma, without signs of LCH and two (8%) are still suffering from recurrent disease. In the overall group eight patients (33%) developed sequelae. Of group C, five patients (63%) are in complete clinical remission, of whom one developed diabetes insipidus as a sequela. Two patients (25%) died and one patient is still suffering from active disease. CONCLUSIONS: If, in addition to supportive treatment, more intensive therapy such as chemotherapy is indicated, we use a regimen containing cytosine-arabinoside, vincristine and prednisolone. This combination is not very aggressive or toxic and has been well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497331 TI - [Surgical thoracoscopy; initial results in 13 patients]. AB - In various diagnostic and therapeutic thoracic operations the use of thoracoscopy can replace the more radical thoracotomy. On account of the development of endoscopic video systems and specialised instrumentation, this technique is increasingly being used. Our first experiences with this new development in thoracic surgery are promising. In the period July 1991-June 1992 we performed 14 thoracoscopic operations in the Merwede Hospital in Dordrecht, for the surgical treatment of spontaneous pneumothorax (8x), for open lung biopsy (5x) and for resection of a peripheral benign tumour of the lung (Ix). No major complications occurred and patient recovery was surprisingly fast. Because of the decreased operation trauma, for several procedures already established via thoracotomy, the surgical thoracoscopy can be regarded as a great improvement in thoracic surgery. PMID- 8497332 TI - [Cost-effectiveness analysis of long-term liver transplantation; the liver transplantation program of Groningen 1979-1991]. AB - A medical technology assessment of the liver transplantation programme of Groningen University Hospital, which was commissioned by the Dutch National Health Insurance Board, is discussed. The results of all 152 liver transplantations performed between 1979 and November 1990 were analysed. The main objective of the study was to evaluate the long-term effects of liver transplantation. Five years after transplantation 59% of the adult patients were still alive. The survival probability depended greatly on the primary liver disease. Mortality and morbidity occurred mainly within the first year after transplantation. Thereafter the prospects for the patients were excellent, with regard to both the probability of survival and the quality of life. The costs of liver transplantation could be calculated only for patients with primary biliary cirrhosis and other forms of biliary cirrhosis, not caused by hepatitis B infection or alcohol abuse. For these patients the costs of a liver transplantation were estimated at HFl. 263,000--(with a 10% margin), 10 years of follow-up included and corrected for the costs that would have been made for the treatment of the liver disease. For this population of patients a liver transplantation costs between Hfl. 64,000--and Hfl. 79,000--per life year gained, 10 years of follow-up included. Costs of cyclosporin still take up a major part of the costs. The need for liver transplantation in the Netherlands was estimated at between 35 and 126 transplantations per year, depending on indications, contraindications, referral policy and the percentage of retransplantations. PMID- 8497333 TI - [Type D Sanfilippo disease in an 8-year-old boy; a rare cause of mental retardation]. AB - This case report describes the history of an 8-year-old boy of full Dutch extraction with mucopolysaccharidosis type III D (Sanfilippo's syndrome type D). Learning problems started at age 5 years; deterioration is only slow at present, and consistent with most of the cases described in literature. Eight of the nine cases described in the literature so far are known to be of Italian origin. Eye investigations showed bilateral peripheral cataract and a fine diffuse white corneal opacity. Ocular abnormalities of this kind have not been reported before in this type of Sanfilippo's syndrome. PMID- 8497334 TI - [Side effects of cholesterol synthesis inhibitors]. AB - Between December 1989 and December 1992, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 142 reports of suspected adverse reactions to simvastatin or pravastatin. In 108 of these, the causal relationship was considered 'definite', 'probable' or 'possible'. The patients were 49 males and 59 females with mean age of 55 and 59 years respectively, with a total of 157 reported suspected adverse reactions. The most important effects reported comprised muscle and vision disorders, interactions with coumarins, liver damage and psychic effects. With the exception of rhabdomyolysis and symptomatic liver damage the adverse effects of cholesterol synthesis inhibitors appear to be fairly innocuous. It should be emphasized, however, that too little is yet known of the psychic and long-term effects for an adequate judgment of the benefit-risk ratio of these agents. PMID- 8497335 TI - [Diagnosis and chemoprevention of perinatal infections caused by group B beta hemolytic streptococci]. PMID- 8497336 TI - Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors. AB - Three novel compounds (WY-48,723, WY-50,324, WY-47,846 [zalospirone]), with high affinity but varying efficacy for the 5-HT1A receptor, were examined for producing the 5-HT behavioral syndrome and for potential antidepressant activity in the forced swimming test (FST). WY-50,324 was more potent than WY-48,723 at producing the 5-HT syndrome, but unlike WY-48,723, it produced only some of the behaviors of the 5-HT syndrome and its profile resembles that of a partial agonist. WY-48,723 appeared to be a full agonist because it produced behavioral effects similar to those of 8-OH-DPAT. The syndrome produced by these compounds was antagonized by pretreatment with pindolol. Zalospirone did not produce the syndrome but it antagonized the syndrome produced by 8-OH-DPAT. WY-48,723 and WY 50,324 reduced immobility time in the FST. These effects were similar to those produced by the tricyclic antidepressant desipramine and the 5-HT1A agonist 8-OH DPAT. Zalospirone did not reduce immobility time, but increased it, which made it difficult to evaluate in this screen. These results suggest that the full agonist WY-48,723 and the partial agonist WY-50,324 may both possess antidepressant activity. Antidepressant-like activity appears to be a characteristic of compounds with a medium to high efficacy for activating 5-HT1A receptors. PMID- 8497337 TI - An increase in the in vivo binding of [3H]SCH 23390 induced by MK-801 in the mouse striatum. AB - The effect of MK-801, a non-competitive NMDA antagonist, on the in vivo binding of [3H]SCH 23390, a dopamine D1 receptor antagonist, was investigated in the mouse brain. The radioactivity following injection of the tracer was measured in the striatum, cerebral cortex and cerebellum. It was found that MK-801 increased the [3H]SCH 23390 binding in the striatum in a dose-dependent manner, but did not influence the binding in the cerebral cortex. The kinetic analysis using the cerebellum as a reference region revealed that the apparent increase in [3H]SCH 23390 binding in the striatum was mainly due to the increase in the input rate of the specific binding component. An in vivo saturation study using varying doses of [3H]SCH 23390 indicated that the maximum binding sites available (Bmax) in the striatum was not altered by MK-801. As the rate constant K3 includes both Bmax and the association rate constant (kon), an increase in the rate constant kon in vivo was the primary factor in the changes in [3H]SCH 23390 binding. The changes in the rate constant kon in vivo seem to be due to a NMDA receptor-mediated process. An in vivo binding method would be applicable for the investigation of the neural interaction between glutamatergic and dopaminergic neurons in intact brain. PMID- 8497338 TI - Effect of ephedrine on muscle weakness in a model of myasthenia gravis in rats. AB - In addition to therapy with anticholinesterases, ephedrine is sometimes used to improve muscle strength in myasthenia gravis, with variable results. The efficacy of ephedrine was tested in rats with a alpha-bungarotoxin-induced model of myasthenia gravis. The rats showed a drooping lower lip and impaired capability of drinking. Injections of neostigmine caused an improvement of the position of the lip. Ephedrine caused some improvement. However, ephedrine had no effect, either on the lower lip or on water consumption, when the sleep-wake cycle was reversed and the rats had their active period during day time. It was concluded that the effect of ephedrine was unspecific and probably due to arousal from drowsiness. The results suggest, therefore, that the variability of the effect of ephedrine in myasthenic patients is unrelated to neuromuscular transmission per se but rather due to a difference in susceptibility to arousal. PMID- 8497339 TI - Cocaine-induced behaviour: dopamine D1 receptor antagonism by SCH 23390 prevents expression of conditioned sensitisation following repeated administration of cocaine. AB - Repeated administration of cocaine (15 mg/kg) (once a week for 4 weeks, day 1, 7, 14 and 21) in a conditioned environment produced significant hyperactivity and head bobbing effects which showed sensitisation. Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg), a dose that blocked d-amphetamine (2.5 mg/kg) induced hyperactivity, antagonised the locomotor effects of cocaine after the second (day 7), third (day 14) and fourth (day 21) administration of cocaine but not the first day (day 1). Antagonism of head bobbing occurred on all 4 (1, 7, 14 and 21) days of treatment. In contrast, haloperidol (0.1 mg/kg) significantly reduced amphetamine-induced hyperactivity but potentiated the locomotor and stereotypic effects of cocaine, after administration of cocaine on days 1 and 7 and had no effect on cocaine-induced behaviour on days 14 and 21. The results suggest that the locomotor effects and head bobbing produced by cocaine, together with the expression of sensitisation to these effects in the conditioned environment, involve activation of post-synaptic D1 receptors. The potentiation of the effects of cocaine by a small dose of haloperidol may indicate increased release of dopamine due to blockade of pre-synaptic D2 autoreceptors. PMID- 8497340 TI - Increased risk of preterm birth in women with cervical conization. AB - OBJECTIVE: To determine the relation between cervical conization and preterm birth. METHODS: All Danish women with singleton pregnancies who gave birth to their first infant in 1982 and second infant during the time period 1982-1987 were included in a register-based cohort study. Information on pregnancy outcome and cervical conization in 1977-1987 was obtained from the Medical Birth Register and the National Register of Hospital Discharges. RESULTS: In a cohort of 14,233 women, 170 had cervical conization. Thirty-four had cervical conization before the first delivery, 62 between the first and the second, and 74 after the second delivery. Women with cervical conization had a significantly higher risk of preterm birth. In addition, women with subsequent cervical conization had a higher risk of preterm birth in previous pregnancies. However, the risk of preterm birth was higher in women with previous than with subsequent cervical conization. CONCLUSIONS: Cervical conization is correlated with preterm birth. Because women with subsequent cervical conization have an increased risk of preterm birth in preceding pregnancies, factors other than the surgical intervention may contribute to the significantly increased risk of preterm birth. PMID- 8497341 TI - Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer. AB - OBJECTIVE: To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed. RESULTS: None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally. CONCLUSION: This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation. PMID- 8497342 TI - Human immunodeficiency virus infection among patients in a gynecology emergency department. AB - OBJECTIVE: To determine the extent of human immunodeficiency virus (HIV) infection risk factors and the relationship to the clinical diagnosis in women seen in a busy inner-city gynecology emergency department. METHODS: We performed a cross-sectional survey by offering routine voluntary HIV-1 antibody screening and obtaining HIV risk behavior profiles in 1033 (35%) of 2952 women seeking care in our gynecology emergency department during a 5-week period. RESULTS: The HIV seroprevalence was 2%. Six (35%) of the infected women reported a history of intravenous drug use, five (29%) reported a history of crack cocaine use, and five (29%) reported no risk factors for infection. Seropositive women were more likely than were seronegative women to have clinical symptoms consistent with pelvic inflammatory disease (18 versus 3%; P < .01). CONCLUSION: These data suggest that women attending the gynecology emergency room in our hospital are at substantial risk for HIV infection. PMID- 8497343 TI - Role of cigarette smoking on the postmenopausal endometrium during sequential estrogen and progestogen therapy. AB - OBJECTIVE: To study the effect of cigarette smoking on the endometrial response to sequentially combined hormone replacement therapy. METHODS: Healthy, early postmenopausal women were randomly assigned to three treatment groups: estradiol (E2) sequentially combined with 75 micrograms of levonorgestrel (19), or 150 micrograms of desogestrel (20), or 10 mg of medroxyprogesterone acetate (18). After 2 years of therapy, the hormone effects on the endometrium were assessed by endometrial histology; effects were also analyzed on biochemical markers of secretion, specifically, secretory endometrial protein (placental protein 14) in serum, and E2 dehydrogenase and isocitrate dehydrogenase in endometrial tissue. Information on smoking habits was elicited by questionnaire. RESULTS: Smokers numbered relatively more women with an atrophic endometrium (50 versus 22%) and proportionally fewer with secretory endometrium (50 versus 78%) (P < .05). The level of serum placental protein 14 was correspondingly almost halved in the smokers (P < .001). The influence of smoking was in part caused by a reduced level of serum E2, but primarily by a non-E2-mediated effect. The E2 effect accounted for 38% of the decrease in serum placental protein 14, and the non-E2 mediated smoking effect for 62%. Endometrial E2 and isocitrate dehydrogenase tended to be lower in smokers, but not after adjustment for the reduced serum E2 level. CONCLUSION: We suggest that smokers may benefit from a hormone combination with a higher dose of E2, even higher than expected as seen from the measurement of serum E2. PMID- 8497344 TI - Complications of laparoscopic hysterectomy. AB - OBJECTIVE: To evaluate complications of laparoscopic hysterectomy. METHODS: A retrospective analysis of complications was tabulated from hospital and office records. Forty-five consecutive patients had laparoscopic hysterectomies from November 1991 to November 1992. Complications were divided into operative, anesthetic, postoperative, nursing, and equipment. Each complication was subjectively graded from mild to severe. RESULTS: Complication rates by group were: operative 11%, anesthetic 7%, postoperative 16%, nursing 4%, and equipment 56%. Operative complications included one bladder perforation, two superficial epigastric artery perforations, and two subcutaneous emphysema cases. There were three anesthetic complications from fluid overload. Postoperative complications included four patients with periumbilical cellulitis. Three patients, who had laparoscopic supracervical hysterectomies, continued to menstruate. Nursing complications included two transient nerve injuries, one femoral and one peroneal. Equipment complications had the highest incidence; the most common type was bipolar cautery dysfunction (22 of 45). There were two video difficulties and one lost laser tip. There were no cases of death, postoperative ileus, fever, thrombophlebitis, transfusions, urinary tract infections, urinary atony, pneumonia, bowel injuries, ureteral injuries, or atelectasis. All patients were treated as outpatients, and no one was admitted or readmitted. Ninety-eight percent of the complications were mild to moderate, with only 2% (one of 45) severe. CONCLUSION: Overall complication rates are high after laparoscopic hysterectomy, even though the complications are predominantly mild to moderate in severity. PMID- 8497345 TI - Evaluation of adhesion formation using Interceed (TC7) absorbable adhesion barrier on ovarian surgical wounds in the rabbit model. AB - OBJECTIVE: To determine whether an Interceed patch would decrease adhesion formation in ovarian surgical wounds healing by second intention in the rabbit model. METHODS: Twenty-five New Zealand White female rabbits underwent midline laparotomy. Using microsurgical technique, each ovary was bivalved longitudinally with a no. 15 blade scalpel, and hemostasis was achieved with bipolar electrocautery. One ovary was then covered with an Interceed patch in a randomized fashion, while the other ovary served as a control. The animals were then allowed to recover routinely. Four weeks later, the rabbits were euthanized and the adhesions were graded by a blinded observer. Adhesion scores between the Interceed-treated ovaries and the control ovaries were compared by Wilcoxon signed-rank test. RESULTS: The mean adhesion score of the Interceed-treated ovaries (1.65 +/- 0.87) was not significantly different from the mean adhesion score of the control ovaries (1.5 +/- 1.0) (P = .51). Some degree of atrophy was noted in 14 of the 50 ovaries. The mean adhesion score in the atrophied ovaries was significantly higher than in the nonatrophied ovaries, regardless of whether the ovaries had been treated with Interceed (2.21 versus 1.40; P = .01). There was no difference in the incidence of atrophy between the Interceed-treated and untreated sides. Exclusion of the ovaries with atrophy again demonstrated no difference in the mean adhesion scores between the treated and untreated sides. CONCLUSION: We were not able to demonstrate any benefit from using Interceed to decrease postoperative adhesion formation of ovarian surgical wounds in the rabbit model. PMID- 8497346 TI - Maternal plasma volume expansion and hormonal changes in women with idiopathic fetal growth retardation. AB - OBJECTIVE: To explore the mechanisms underlying the reduced maternal plasma volume associated with idiopathic fetal growth retardation (FGR). METHODS: In 30 normotensive women with growth-retarded fetuses and 26 with normal-size fetuses, plasma volume was measured with a modified Evan's blue method. Plasma levels of atrial natriuretic peptide, plasma renin activity, aldosterone, estradiol, and progesterone, and urinary excretion of kallikrein, prostacyclin, and thromboxane A2 were measured at 34-40 weeks' gestation. RESULTS: Compared with controls, gravidas with growth-retarded fetuses had a reduced plasma volume expansion (P < .01), similar atrial natriuretic peptide and plasma renin activity levels, and lower serum aldosterone (P < .001) and placental steroids (P < .03). These women also had decreased urinary kallikrein activity and prostaglandin excretion (P < .05). When both groups were combined, maternal plasma volume correlated significantly with birth weight (r = 0.53) and placental weight (r = 0.66). CONCLUSION: Normotensive women with idiopathic FGR have reduced plasma volume expansion. Although the exact mechanisms of this change are unknown, we postulate that the lower maternal aldosterone levels and reduced levels of vasodilator substances, such as prostacyclin and kallikrein, may have a causal role. PMID- 8497347 TI - Evaluation of a new generation of oral contraceptives. The Advisory Board for the New Progestins. AB - OBJECTIVE: To assess the differences and similarities in efficacy, safety, and metabolic effects of oral contraceptives (OCs) containing the new progestins desogestrel, gestodene, and norgestimate. All formulations reviewed contained no more than 35 micrograms ethinyl estradiol. DATA SOURCES: Data were reported from approximately 100 published reports, dating from 1980, of comparative and noncomparative clinical studies on phasic and fixed-dose preparations culled from computer searches of several sources, including MEDLINE and Excerpta Medica. METHODS OF STUDY SELECTION: An attempt was made to select the most meaningful studies in terms of length, size, methodology, and quality of description. All clinical studies were considered; in general, review articles were not. Some preclinical studies were also included. No abstracts were used. DATA EXTRACTION AND SYNTHESIS: The indices chosen for examination were contraceptive efficacy, cycle control, coagulation, carbohydrate and lipid metabolism, and androgenicity. CONCLUSIONS: The new formulations were found to be comparable in efficacy to each other and to established agents. They also appeared to be less androgenic than current OCs and to have less impact on carbohydrate and lipoprotein metabolism. Cycle control was similar to that of older products. Changes in coagulation promoting and antithrombotic factors were minor. Clinical relevance of the results could not be determined because of small sample size and methodologic differences between studies. PMID- 8497348 TI - The physician as advertiser: the unintentional discouragement of breast-feeding. AB - To be consistent with national health goals and ACOG policies and recommendations, physicians providing prenatal care should encourage breast feeding whenever possible. The parents' choice to breast- or formula-feed their infant is the consequence of a complex decision. The physician's role is to provide information objectively so that the parents' decision can be made on an informed and factual basis. Clearly, the physician must support parents' decisions. However, the distribution of formula or vouchers in the physician's office during the antepartum period places the physician in the position of advertising or promoting a specific product and of potentially contributing to the failure of some patients to nurse their infants. We urge physicians not to distribute formula or formula vouchers to their pregnant patients, and encourage local and national obstetrics organizations to consider devising and discussing a policy statement discouraging such practices. PMID- 8497349 TI - A physician's prerogative to prescribe drugs for off-label uses during pregnancy. AB - Physicians frequently prescribe drugs for indications other than those on the product label. Reasons for such off-label use during pregnancy include: prevention of repetitive abortion, inhibition of premature labor, reduction of fetal or neonatal infection, reduction in development of preeclampsia and its complications, and ripening of the cervix or induction of labor. A physician has a legal right to prescribe for off-label indications despite regulatory, manufacturer, and cost constraints. Such prescribing habits would not be considered experimental if based on sound scientific evidence. Adequate and well controlled studies are difficult to perform during pregnancy. Evidence of widespread use and support from another qualified clinician are methods of justifying off-label prescribing. Each patient is entitled to know why she and her fetus would benefit from the treatment and whether any unnecessary risk is anticipated. Legible documentation of these discussions in the medical records is important. PMID- 8497350 TI - An obstetric scoring system: its development and application in obstetric management. PMID- 8497351 TI - Cervical dilation: accuracy of visual and digital examinations. PMID- 8497352 TI - Reduction in very low birth weight deliveries and perinatal mortality in a specialized, multidisciplinary twin clinic. PMID- 8497353 TI - A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation. AB - OBJECTIVE: To determine whether continuous intrapartum electronic fetal heart rate monitoring (EFM) is associated with decreased perinatal mortality and morbidity compared with intermittent auscultation. METHODS: The study was conducted simultaneously at two university hospitals in Athens, Greece (Alexandra and Marika Iliadi Hospitals) from October 1, 1990 to June 30, 1991. All patients with singleton living fetuses and gestational ages of 26 weeks or greater were eligible for inclusion. The participants were assigned to continuous EFM or intermittent auscultation based on the flip of a coin. Both groups were followed during labor according to the most recent ACOG guidelines. However, fetal scalp blood pH and crossover from one group to the other were not used. RESULTS: A total of 1428 patients were included, 746 in the EFM group and 682 in the auscultation group. There were no differences between the groups in terms of maternal age, gravidity, parity, gestational age, and number of antepartum high risk factors. More patients monitored electronically received oxytocin for either augmentation (52.4 versus 38.1%; P = .0001) or induction (15.6 versus 7%; P = .0001). The length of labor was longer in the EFM group (first stage 6.1 +/- 4.3 versus 5.5 +/- 3.7 hours; P = .006; second stage 29.4 +/- 18.6 versus 26.9 +/- 16.9 minutes; P = .01). There was a higher incidence of nonreassuring fetal heart rate patterns in the EFM group (23.4 versus 10.7%; P = .0001) and a higher rate of surgical intervention (11.2 versus 4.8%; P = .0001). This difference pertained to both vacuum extraction (5.8 versus 2.4%; P = .002) and cesarean delivery for suspected fetal distress (5.3 versus 2.3%; P = .005). There were no differences in 1- and 5-minute Apgar scores, fetal acidosis at birth, need for neonatal resuscitation, neonatal intensive care unit admission, use of assisted ventilation, neonatal hospital stay, or any other neonatal complications. Two neonatal deaths occurred in the EFM group and nine perinatal deaths in the auscultation group (two intrapartum and seven neonatal deaths). The perinatal mortality rates were 2.6 per 1000 and 13 per 1000 total births, respectively (P = .04). The two deaths in the EFM group and three of the neonatal deaths in the auscultation group may not have been prevented by intrapartum monitoring; however, four neonatal deaths from the auscultation group occurred in depressed (5-minute Apgar scores less than 7), acidotic (cord artery pH at or below 7.13) infants. The perinatal death rate related to fetal hypoxia was significantly less in the EFM group (zero of 746 versus six of 682; P = .03). CONCLUSION: In this controlled trial, intrapartum EFM, as the primary and only method of intrapartum fetal surveillance, was associated with decreased perinatal mortality due to fetal hypoxia but also with higher rates of surgical intervention for suspected fetal distress. PMID- 8497354 TI - Nicardipine treatment of hypertension during pregnancy. AB - OBJECTIVE: To assess the effects of nicardipine, a dihydropyridine calcium channel blocker, on the fetus and mother in hypertensive pregnant women. METHODS: Forty pregnant patients with mild or moderate hypertension received oral nicardipine 20 mg three times a day (mean duration of treatment 9 +/- 2.1 weeks). Twenty patients with severe preeclampsia (diastolic blood pressure greater than 110 mmHg and 24-hour proteinuria greater than 500 mg) received intravenous (IV) nicardipine at 2, 4, or 6 mg/hour according to body weight (mean duration of treatment 5.3 +/- 3.6 days). RESULTS: Oral nicardipine induced a significant decrease in both systolic and diastolic blood pressures compared with pre treatment values (P < .001). Intravenous nicardipine decreased diastolic blood pressure below 90 mmHg, at least temporarily, in all 20 patients. Nine patients taking IV nicardipine complained of headaches. Doppler velocimetry remained stable with both oral and IV nicardipine. Neonatal outcome showed no deleterious effect of the treatment. CONCLUSIONS: Oral or IV nicardipine seems to be safe in hypertensive pregnant patients with the doses used in our study. Assessment of its efficacy will necessitate further clinical randomized trials. PMID- 8497355 TI - Abnormal cervical cytology in pregnancy: a 17-year experience. AB - OBJECTIVE: To evaluate the safety and accuracy of colposcopy and colposcopically directed biopsy in pregnant women with abnormal cervical cytology. METHODS: A retrospective analysis of 612 gravidas with abnormal cervical cytology was conducted. Colposcopy and directed biopsy were performed using standard techniques. Two patients underwent diagnostic conization during the second trimester. One hundred twelve patients had procedures that provided a final specimen. Endocervical curettage was omitted. The transformation zone was fully visualized in all patients by the 20th week of gestation. Directed cervical biopsy was performed on the following patients: 1) with colposcopic evidence of invasion or cervical intraepithelial neoplasia (CIN) III, 2) with discordancy between colposcopy and cytology, 3) electing termination of pregnancy, and 4) whose anticipated reliability was even remotely questioned. RESULTS: A colposcopically directed biopsy was performed in 449 patients (73%). Ninety-one patients (15%) did not have biopsies because of normal colposcopic findings, and the remaining 72 patients (12%) had either CIN I or II. Thirty-nine of these patients (6%) were lost to follow-up. Colposcopically directed biopsy and colposcopic impression had a 95% concordancy within one degree of severity; however, 14% of CIN I colposcopic impressions and 54% of normal colposcopic findings turned out to be CIN III and CIN I or II, respectively. Ninety-five percent of the biopsy diagnoses correlated with the final pathology to within one degree of severity. CONCLUSION: The data confirm previous findings that colposcopically directed biopsy is a safe and reliable method of evaluating pregnant patients with abnormal cervical cytology. PMID- 8497356 TI - The need for adjustment of dosage regimen of penicillin V during pregnancy. AB - OBJECTIVE: To determine whether the normal regimen of dosage of oral penicillin V is relevant during pregnancy. METHODS: Twelve pregnant and six nonpregnant women volunteered for the study. Six women were in the second trimester of pregnancy (mean +/- standard deviation 19 +/- 7 weeks' gestation) and six women were in the third trimester (35 +/- 2 weeks). All of the women took 1 x 10(6) IU phenoxymethylpenicillin orally, and multiple blood and urine samples were obtained. Assays were performed by means of a disk agar diffusion method. The results were compared by Mann-Whitney U test. RESULTS: Compared with nonpregnant women, pregnant women had smaller area under the curve values (433 +/- 93 minutes.IU/mL, P < .05 in the second trimester; 550 +/- 220 minutes.IU/mL in the third trimester) and a shorter half-life (57 +/- 56 minutes in the second trimester; 34 +/- 21 minutes, P < .05 in the third trimester). Plasma and renal clearances were faster in the pregnant women. CONCLUSION: Elimination of penicillin V is enhanced during pregnancy, necessitating either a shorter dosing interval (6-8 hours) or an increased dose with the standard dosing interval. PMID- 8497357 TI - Preoperative skin preparation and intraoperative pelvic irrigation: impact on post-cesarean endometritis and wound infection. AB - OBJECTIVE: To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population. METHODS: A randomized study was performed in 100 cesarean patients. Subjects were assigned to one of four groups, involving either standard skin preparation (povidone-iodine [7.5%] scrub followed by povidone-iodine [10%] solution) or special skin preparation (5 minute scrub with parachlorometaxylenol followed by povidone scrub and solution), and either normal saline or antibiotic (cefazolin sodium, 1 g in 500 mL normal saline) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure. Four groups of patients were formed: standard skin preparation plus normal saline irrigation, standard preparation plus antibiotic irrigation, special preparation plus normal saline irrigation, and special preparation plus antibiotic irrigation. RESULTS: Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation (P < .001). In contrast, comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference (P = .22). CONCLUSION: Skin preparation with an antibacterial scrub in addition to standard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution. PMID- 8497358 TI - Pregnancy and delivery in women with a traumatic spinal cord injury in Sweden, 1980-1991. AB - OBJECTIVE: To evaluate the incidence of delivery in women after a traumatic spinal cord injury and to describe pregnancy outcome in this group of patients. METHODS: Between 1980-1991, 29 women with a traumatic spinal cord injury experienced 49 pregnancies and gave birth to 52 children in Sweden. A retrospective chart review of the antepartum, intrapartum, and perinatal records of these patients was performed. In addition, all patients participated in a telephone interview held by one of the authors. Of the 29 women, 12 had lesions above T5 and 17 had lesions at T5 or below. RESULTS: Antenatal complications occurred frequently in this group. Nine of 12 patients with lesions above T5 had symptoms of autonomic hyperreflexia during pregnancy and/or delivery. Only in a minority of the women was the problem recognized by the medical professionals. Nine of the infants (19%) were born preterm and two were small for gestational age. The perinatal mortality rate was two of 52 (3.8%) and occurred in two cases of abruptio placentae. Few of the patients were allowed to deliver vaginally. The cesarean delivery rate for women with lesions above T5 was 47% and for women with lesions below that level, 26%. CONCLUSION: The overall prognosis for these women was favorable. However, women with higher spinal cord lesions would probably benefit from referral to centers with a particular interest and expertise in the management of their problems. PMID- 8497359 TI - Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. AB - OBJECTIVE: To define the relationships between neonatal opiate withdrawal and drug-related factors such as maternal methadone dosage, maternal and neonatal plasma levels, and rate of decline of methadone in neonatal plasma. METHODS: Twenty-one methadone-dependent women and their newborn infants were studied. Fourteen of the women used other illicit drugs. The severity of neonatal withdrawal was assessed with a standardized scoring system. Venous blood samples for methadone levels were collected from the mothers within 24 hours of delivery and from their newborns within 24 hours of birth and on day 3-4 of life. RESULTS: The maternal methadone dosage at delivery correlated significantly with the maternal plasma level drawn at 16 hours postpartum (r = 0.512, P < .05), and the maternal methadone level in turn correlated significantly with the neonatal plasma methadone level on day 1 of life (r = 0.545, P < .05). A positive correlation was found between the severity of central nervous system signs of withdrawal and the rate of decline of the neonatal plasma methadone level from day 1 to day 4 of life (r = 0.550, P < .05). CONCLUSION: This spectrum of relationships supports the concept that careful reduction of the maternal methadone dosage during pregnancy under intensive medical and psychosocial surveillance may benefit the drug-exposed new-born infant clinically. PMID- 8497360 TI - The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. AB - OBJECTIVE: To assess the association between cytokines in the amniotic fluid (AF) and preterm delivery, the isolation of bacteria from the AF or chorioamnion, and histologic chorioamnionitis. METHODS: Fifty afebrile women with intact membranes in preterm labor at or before 34 weeks' gestation underwent amniocentesis. Cytokine levels were measured in AF, and cultures were performed. Placentas were cultured and examined histologically. RESULTS: Thirty-two (64%) of the 50 patients delivered at or before 34 weeks' gestation. Delivery at or before 34 weeks, compared with delivery after 34 weeks, was related to increased levels of interleukin-6 (IL-6) (88 versus 12%; P < .001), interleukin-1 (IL-1) alpha (50 versus 6%; P = .004), IL-1 beta (42 versus 0%; P = .002), and prostaglandin (PG) E2 (66 versus 22%; P = .008). Bacteria were recovered from the AF of nine (18%) of the 50 patients. All of the cytokines with increased levels, plus tumor necrosis factor (TNF)-alpha, were related to bacteria in the AF. Increased IL-6, IL-1 alpha, IL-1 beta, TNF-alpha, and PGE2 were also associated with histologic chorioamnionitis among women who delivered within 1 week of amniocentesis. Elevated cytokine levels were not related to chorioamnion infection. CONCLUSIONS: Elevated AF cytokines and PGE2 predicted delivery before 34 weeks' gestation and delivery within 7 days of the amniocentesis, as well as AF infection and histologic chorioamnionitis. These findings support the hypothesis that infection is one cause of preterm delivery, operating via a mechanism involving induction of cytokine production. PMID- 8497361 TI - The role of fetal growth restriction and gestational age on length of hospital stay in twin infants. AB - OBJECTIVE: To evaluate the association between length of gestation and fetal growth restriction (FGR) and the role of FGR in neonatal morbidity as determined by length of hospital stay among newborn twins. METHODS: Using a race-, gender-, and gestational age-specific birth weight and length of hospital stay singleton standard, 490 twin infants were classified as FGR (at or below the tenth percentile) or non-FGR (above the tenth percentile). Length of stay and length-of stay ratio (twin stay divided by the 50th percentile singleton stay) were calculated for each twin. Analysis included stepwise multiple regression for length of stay and length-of-stay ratio, and analysis of variance with main effects and second-order interactions for the length-of-stay measures using factors significant in the multiple regression models. RESULTS: For length of stay, significant factors in the multiple regression model included respiratory distress syndrome (RDS), gestation category, FGR, sepsis, time of birth (1979 1984 versus 1985-1989), and cesarean delivery. For length-of-stay ratio, significant factors included FGR, gestation category, sepsis, period of birth, cesarean delivery, and hyperbilirubinemia. The analysis of variance showed that RDS had the greatest effect on length of stay, whereas FGR had the greatest effect on length-of-stay ratio. For both dependent variables, the effect of FGR was magnified when compounded by significant neonatal complications (RDS, sepsis, hyperbilirubinemia) or gestation category. CONCLUSIONS: Fetal growth restriction is a major factor in the neonatal morbidity of twins. Early recognition of and interventions for FGR in twin gestations should be a primary goal for reducing both immediate and long-term adverse outcomes. PMID- 8497362 TI - The prognostic value of hemoglobin A1c in predicting fetal heart disease in diabetic pregnancies. AB - OBJECTIVE: To evaluate detailed fetal echocardiography for predicting congenital heart disease in overt diabetic pregnancies. METHODS: Overt diabetic gravidas with initial hemoglobin A1c (HbA1c) at or above 8.5%, a family history of congenital heart disease, or fetal cardiac anomaly suspected on screening sonography were referred to a pediatric cardiologist for detailed fetal echocardiography. After 7 years, the results of the protocol were reviewed retrospectively. The sensitivity and specificity of the initial HbA1c in predicting congenital heart disease were assessed. RESULTS: During the study period, 193 patients received care in the diabetes and pregnancy service. Sixty four received fetal echocardiography, 47 because of initial HbA1c levels at or above 8.5% and 17 for other indications. Twenty fetuses had major anomalies, eight of which were cardiac (40%). Six of the cardiac anomalies had been studied by fetal echocardiography, and four were diagnosed correctly. The initial HbA1c was not different among pregnancies with major anomalies, cardiac anomalies, or no anomalies. No malformations were noted in patients with normal initial HbA1c values. The overall sensitivity of the protocol for identifying congenital heart disease was 50% (four of eight) and specificity was 54% (90 of 167). Detailed fetal echocardiography had a sensitivity of 66% (four of six) and a specificity of 100% (58 of 58) for correctly identifying fetal congenital heart disease. CONCLUSIONS: No cases of congenital heart disease were observed in patients with a normal initial HbA1c value. Among patients with abnormal HbA1c values, no critical level of glycohemoglobin was identified that provided optimal predictive power for congenital heart disease screening. We recommend detailed fetal echocardiographic imaging in all patients with initial HbA1c levels above the upper limit of normal of 6.1%. PMID- 8497363 TI - Acid-base and hematologic values at blood sampling in the evaluation of trisomic fetuses: a case-control study. AB - OBJECTIVE: To investigate whether nonhydropic trisomic fetuses display specific alterations of acid-base and/or hematologic values. METHODS: Acid-base and hematologic variables were analyzed in 28 trisomic fetuses (12 with trisomy 21 and 16 with trisomy 18) and 28 chromosomally normal controls matched for gestational age and fetal size undergoing fetal blood sampling at 18-36 weeks' gestation. RESULTS: There were no differences between the groups in pH, oxygen pressure, carbon dioxide pressure, and base excess. Compared with matched controls, hematocrit, hemoglobin, and red blood cell counts were significantly higher in fetuses with trisomy 21 and significantly lower in those with trisomy 18. All other hematologic variables were similar in trisomic fetuses and their controls. CONCLUSIONS: Growth retardation in trisomic fetuses is associated with decreased oxygen supply, as it is in chromosomally normal growth-retarded fetuses. The higher perinatal mortality that occurs with trisomies 21 and 18 is not explained by more pronounced hypoxemia for a given degree of growth retardation. There is no specific association of acid-base and hematologic values that is diagnostic of chromosomal abnormality at fetal blood sampling. PMID- 8497364 TI - Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. AB - OBJECTIVE: To assess the efficacy of 0.75% metronidazole vaginal gel, formulated at pH 4.0, for the treatment of bacterial vaginosis in a double-blind, placebo controlled crossover trial. METHODS: Fifty-three women with bacterial vaginosis (clue cells of at least 20% plus vaginal pH of at least 4.7, amine odor, or homogeneous discharge) were enrolled. Women with concomitant infection by Candida, Trichomonas, Chlamydia trachomatis, or Neisseria gonorrhoeae were excluded. Five grams of metronidazole gel or placebo was inserted intravaginally twice daily for 5 days. Response to therapy was evaluated at 4-16 days and 1 month after treatment. RESULTS: Twenty-six of the 30 women (87%) who received metronidazole were free of bacterial vaginosis 9-21 days after enrollment, compared with only four (17%) of 23 placebo-treated women (P < .001). Women who were cured were followed prospectively. Those who had persistent bacterial vaginosis were crossed over to metronidazole gel in an open trial; bacterial vaginosis was eradicated in 21 of 23 (91%) of these women at the 2-week follow up. Recurrent bacterial vaginosis developed within 1 month in four (15%) of 26 women who were initially cured after receiving metronidazole gel. Response to therapy was accompanied by a decrease in vaginal Bacteroides, Gardnerella vaginalis, and Mycoplasma hominis. CONCLUSIONS: Treatment with intravaginal metronidazole gel resulted in a clinical cure in 87% (placebo-controlled trial) to 91% (crossover trial) of women with bacterial vaginosis. The recurrence rate of 15% at 1 month after treatment is similar to that reported with oral metronidazole. PMID- 8497365 TI - Cost-effectiveness of strategies to evaluate postmenopausal bleeding. AB - OBJECTIVE: To identify an optimal evaluation strategy for patients of various ages and risks for endometrial cancer and for complex hyperplasia who present with a first episode of postmenopausal bleeding. METHODS: We constructed a decision-analytic model to assess the life expectancy, effectiveness, cost, and cost-effectiveness of four options for the initial evaluation of postmenopausal bleeding: office endometrial biopsy, D&C, hysterectomy, and observation unless bleeding recurred. We considered patients at different ages and risks for cancer and for complex hyperplasia. RESULTS: Life expectancy was similar for all four strategies, but overall expected costs varied markedly. Compared with the other procedures, office biopsy was the most cost-effective initial strategy, costing less than $41,000 per year of life saved for patients at moderate combined risk (ie, 10%) of cancer or complex hyperplasia. However, for patients at low risk (ie, 5%), even office biopsy was relatively costly in certain age groups, with costs as high as $205,000 per additional year of life saved for 80-year-old patients. Both D&C and hysterectomy were more costly and no more effective than office biopsy as initial evaluation strategies in all patient groups over a wide range of changes in baseline assumptions. CONCLUSIONS: Office biopsy is always preferred over D&C or hysterectomy for the initial evaluation of patients with postmenopausal bleeding. However, one may consider delaying a biopsy unless and until bleeding recurs for patients who are at low risk (5% or less) for cancer and complex hyperplasia by clinical criteria. PMID- 8497366 TI - Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins. AB - OBJECTIVE: To determine the effect of large-loop excision of the transformation zone (LLETZ) on the ability to interpret adequately the pathologic specimen and surgical margins. METHODS: Fifty consecutive LLETZ specimens were used for repeat histopathologic assessment with emphasis on the interpretability of the surgical specimen and margin. All reevaluations were performed by a single pathologist. Complete lesion evaluability was defined as satisfactory accuracy of the histologic diagnosis and the ability to evaluate thoroughly all surgical margins. Medical records of the patients from whom the specimens were obtained were reviewed and analyzed for possible correlates to the status of specimen interpretability. RESULTS: Histologic accuracy was sufficient in 46 cases (92%). Extensive heat distortion precluded full assessment of the ectocervical margins in ten (20%) and the endocervical margins in 22 (44%) of the cases. There was no difference in complete lesion evaluability whether LLETZ was performed solely for treatment in cases suitable for ablative procedures or for both diagnosis and treatment in patients who traditionally would have undergone a cone biopsy. If the latter group (N = 25) was analyzed separately, extensive heat distortion made histopathologic diagnosis impossible in four cases (16%) and precluded full assessment of the ectocervical margin in eight (32%) and the endocervical margin in 12 (48%). CONCLUSION: The high rate of surgical-margin thermal destruction, with related limitation of interpretability, may represent a serious diagnostic and therapeutic limitation of the LLETZ procedure when considered as an alternative to cold knife conization. PMID- 8497367 TI - Comparison of Doppler with two-dimensional sonography and CA 125 for prediction of malignancy of pelvic masses. AB - OBJECTIVE: To assess the validity of Doppler flow sonography for the prediction of malignancy in adnexal masses and to compare the results with two-dimensional ultrasonographic examination and CA 125 levels. METHODS: In a cross-sectional study, 55 patients with adnexal masses were examined using Doppler sonography to measure the resistance index of tumor-associated blood flow profiles. In addition, abdominal and transvaginal ultrasound examinations were performed and preoperative CA 125 serum levels were assessed. RESULTS: Sixteen patients had malignant tumors and 39 had benign tumors. A resistance index cutoff of less than or equal to 0.8 showed the highest sensitivity (93.8%), with a specificity of 56.4%, a positive predictive value of 46.8%, and a negative predictive value of 95.7%. Compared with two-dimensional sonographic evaluation using either a scoring system or subjective assessment, and with CA 125 levels, the resistance index showed higher sensitivity and negative predictive value but lower specificity and positive predictive value. False-positive resistance index values were prevalent with endometriosis, leiomyomata, and mucinous cystadenoma. The combination of the resistance index with either the sonographic features or CA 125 increased the sensitivity and negative predictive value to 100%, with only a slight decrease in specificity and positive predictive value, but was not superior to the combination of two-dimensional sonography and CA 125. CONCLUSION: Doppler sonographic evaluation of resistance indexes in the vessels of adnexal masses increased the sensitivity of two-dimensional sonography and CA 125. However, 46% of positive Doppler results were false and 37.5% of the benign tumors had low resistance indexes, thus limiting the validity of this technique for screening programs. PMID- 8497368 TI - Relationship between saliva and serum CA 125 in women with and without epithelial ovarian cancer. AB - OBJECTIVE: To determine the distribution of saliva CA 125 levels in women with and without ovarian cancer, and to determine whether there is a correlation between saliva and serum CA 125 levels in either group. METHODS: CA 125 levels were measured by immunoradiometric assay in the serum and saliva of 50 women with epithelial ovarian cancer known to have elevated serum CA 125 levels (above 35 U/mL) and in 50 women seen for benign gynecologic conditions. RESULTS: Serum and saliva CA 125 values followed a log-normal distribution in both groups. The medians for serum and saliva CA 125 levels in cancer patients were 578 and 1379 U/mL, respectively. In the benign group, the median CA 125 value was 11 U/mL in serum and 994 U/mL in saliva. The correlation between saliva and serum CA 125 levels was not statistically significant in either the cancer (r = 0.003) or the benign group (r = 0.025). CONCLUSION: There is no relationship between saliva and serum CA 125 levels in women with either epithelial ovarian cancer or benign gynecologic conditions. PMID- 8497369 TI - Where babies are born and who attends their births: findings from the revised 1989 United States Standard Certificate of Live Birth. AB - OBJECTIVE: To examine the results of changes in the birth certificate with regard to characteristics of the mothers and the birth weights of their infants. The United States Standard Certificate of Live Birth was revised in 1989 to include specific designations for the place of births out of hospital and the presence of a nurse-midwife or other midwife at the birth. METHODS: All results are based on data from the Natality, Marriage and Divorce Statistics Branch of the National Center for Health Statistics, Centers for Disease Control. In all cases reported here, the data represent at least 91% of all United States births in 1989. RESULTS: Different patterns of birth attendance emerged in different settings. In residential births, other midwives and "others" attended 66% of all births, whereas in freestanding birth centers, physicians and certified nurse-midwives attended 75.1% of all births. The characteristics of the mothers differed substantially according to who attended their births in these settings. Substantial interstate variations in place and attendant were also documented. CONCLUSION: The positive outcomes achieved in certain settings indicate a need for further research into the factors that influence birth outcomes. PMID- 8497370 TI - Sodium butyrate inhibits the enhancing effect of high fat diet on mammary tumorigenesis. AB - We have studied the effect of butyrate on mammary tumorigenesis by 7,12 dimethylbenz(a)anthracene. As reported previously, a high incidence of mammary tumors was observed in rats fed a basal diet containing 20% margarine. However, the enhancing effect of margarine was inhibited when sodium butyrate was supplemented in the high margarine diet. Sodium butyrate did not cause any effect when it was supplemented in the basal diet. The result suggests a possibility that a part of the inhibitory effect of butter on mammary tumorigenesis, which we had previously reported, was caused by butyrate milk lipids. PMID- 8497371 TI - Effect of cyclic cisplatin and etoposide therapy with continuous UFT administration on the recurrence of endometrial cancer in nude mice. AB - Effects of cisplatin and etoposide chemotherapy and/or continuous administration of oral anticancer agent UFT following the initial chemotherapy with cisplatin and etoposide on the tumor recurrence rate were studied in endometrial cancer bearing mice. Complete response (CR) rate of cyclic administration of cisplatin and etoposide (91%) was significantly higher than that in the control group (60%; p < 0.05). Continuous UFT administration raised a CR rate of 75%, which was not significantly higher than that of the control group. When cyclic administration of cisplatin and etoposide was combined with continuous UFT administration, 100% of CR rate was obtained (p < 0.01). Our results suggest that cisplatin-based cyclic chemotherapy has a therapeutic effect on gynecologic malignancies and is particularly effective in preventing tumor recurrence in mice. Combining this therapy with continuous administration of an oral anticancer agent enhances its therapeutic effect. PMID- 8497372 TI - Tissue distribution of cis-diamminedichloroplatinum(II) following intraperitoneal administration to patients with recurrent gastric cancer. AB - Using atomic absorption spectrophotometry, we determined the concentration of platinum in tissues obtained at autopsy of 4 patients with recurrent gastric cancer. Patients had been given intraperitoneal cis-diamminedichloroplatinum(II) (cisplatin, CDDP). There was no correlation between the concentration of platinum and the dose of CDDP. Platinum was distributed in all organs examined, the highest amount being in the liver. Thus, when CDDP is administered intraperitoneally for treatment of patients with malignant disease, the toxicity to various organs, including the liver and the kidney, needs to be considered. PMID- 8497373 TI - Transient increase in total serum alkaline phosphatase predicts radiological response to systemic therapy in breast cancer patients with osteolytic and mixed bone metastases. AB - Assessment of the response of bone metastases to endocrine or chemotherapy is difficult, and true response rate is probably underestimated by UICC criteria. Biochemical markers of osteoblast activity, which is linked with bone healing, could be useful for early detection of treatment response. We studied changes in osteoblast function, assessed by serial serum total alkaline phosphatase (tALP) at 0, 1, 2, 3 months from the start of systemic therapy, in 31 patients bearing bone metastases from advanced breast cancer. After 1 month of endocrine or cytotoxic treatment, all responding patients (7/31) showed a significant rise in tALP (mean increase: 351 IU/l, p < 0.05) followed by a gradual decrease over the subsequent months (tALP flare). Transient increase in tALP was also found in 2/16 patients with stable disease who benefited from therapy. 2/8 patients with progressive disease showed a rise indistinguishable from responders, but the subsequent decrease was not apparent. These observations suggest that serum tALP profile is an earlier predictor of response than X-rays. PMID- 8497374 TI - Lifelong menstrual pattern and risk of breast cancer. AB - The relationship between lifelong menstrual pattern and the risk of breast cancer has been analyzed using data from a large case-control study conducted since 1983 in the greater Milan area including 3,037 cases, aged 74 years or less, with histologically confirmed breast cancer and 2,569 control subjects admitted for acute nongynecological, nonneoplastic nonhormone-related conditions to the same network of hospitals where cases had been identified. Compared with women reporting lifelong regular cycles, those reporting irregularities were at significantly reduced risk of breast cancer, relative risk estimate being 0.6, with 95% confidence interval (CI) ranging from 0.5 to 0.8. This protection was restricted to women reporting totally irregular menstrual cycles; compared to women reporting menstrual cycles lasting 25 days or less, the estimated relative risks were 1.0 and 1.2 in those reporting cycles lasting 26-30 days or 31 days or more, respectively, but 0.6 (95% CI 0.5-0.8) for those reporting totally irregular cycles. The effect of irregular menstrual cycles was similar in different strata of age and main risk factors for breast cancer. PMID- 8497375 TI - Tamoxifen or cyproterone acetate in combination with buserelin are ineffective in patients with pancreatic adenocarcinoma. AB - Experimental evidence and preliminary clinical data suggest a responsiveness of pancreatic adenocarcinoma to sex hormones and LH-RH agonists. In this study, we investigated the effect of the antiestrogen tamoxifen and the antiandrogen cyproterone acetate in combination with the LH-RH agonist buserelin in 9 patients with unresectable pancreatic adenocarcinoma. In all patients the disease was progressive under this therapeutic regimen. In conclusion, complete androgen blockade and antiestrogens in combination with LH-RH agonist cannot be recommended in patients with widespread pancreatic adenocarcinoma. PMID- 8497376 TI - Changes in intracellular magnesium concentrations during cisplatin chemotherapy. AB - Magnesium is mainly an intracellular cation, and its availability is not represented reliably by plasma levels. The effects of cisplatin on Mg concentrations in plasma (PMg) and erythrocytes (EMg) were investigated in 22 neoplastic patients. Assays were done before and 1, 2, 4 and 7 days after cisplatin administration; 10 patients were also checked following six courses of chemotherapy. PMg decreased progressively either day by day after a single dose of cisplatin (p < 0.001 on the 7th day) or month by month after cumulative doses (p < 0.05 after two courses and p < 0.001 after six). EMg decreased till the 4th day (p < 0.001), but recovered pretreatment levels on the 7th day; an actual depletion was manifested only after the third course of chemotherapy (p < 0.05) and became more marked after the 6th. These results suggest that, besides renal Mg wasting, Mg metabolism is influenced by cisplatin also at a cellular level. The cisplatin-induced injury on membrane transport systems, where Mg is abundant and plays an important stabilizing role, might induce an early shift of Mg from cells into the blood stream. When repair systems begin to act, Mg is taken up from plasma to recover the normal cellular content. The lack of an actual depletion of Mg body stores till the third course of chemotherapy possibly makes the early Mg supplementation commonly administered before or contemporaneously to cisplatin infusion unnecessary. Oral supplements between the courses might be sufficient to prevent Mg depletion without exposing the patients to the risk of hypermagnesemia in case of cisplatin-induced acute renal failure. PMID- 8497377 TI - Effect of human granulocyte colony-stimulating factor on neutropenia induced by radiotherapy and chemotherapy. AB - This study was designed to test the effect of human granulocyte colony stimulating factor (hG-CSF) in patients at risk for neutropenia caused by radiotherapy plus chemotherapy. Twelve patients with advanced esophageal tumor were treated after operation with 'sandwich' radiochemotherapy (successive treatment with chemotherapy-radiotherapy-chemotherapy). hG-CSF was given subcutaneously at a dose of 2 micrograms/kg/day for 3-5 days after the white blood cell counts decreased to less than 3,000/mm3. Neutrophil counts significantly recovered to normal levels within 5 days in all patients treated with hG-CSF. No significant changes in the lymphocyte, platelet and red blood cell counts were shown. No side effects were observed. These results indicate that hG-CSF is a useful tool for the treatment of neutropenia induced by radiotherapy and chemotherapy. PMID- 8497378 TI - Postirradiation sarcoma in a patient treated for testicular seminoma. AB - A patient with a sarcoma of the left groin at a site where a prior seminoma had been irradiated is presented. Very few postirradiation sarcomas are described in patients treated with radiation therapy for testicular cancers, even if an increased risk of second malignancies has been reported. In contrast with the highly aggressive clinical course of postirradiation sarcomas, an early discovery of the lesion allowed a radical surgical approach with a presumable cure of the patient. A continuous and precise follow-up of patients irradiated for seminoma is suggested. PMID- 8497379 TI - Induction of hepatocellular carcinomas in the Egyptian toad Bufo regularis by an antifungal drug (griseofulvin). AB - Neoplastic lesions (hepatocellular carcinomas) were induced in the liver in 18 of 100 experimental toads (Bufo regularis) force fed with the antifungal drug griseofulvin, at a dose level of 0.4 mg/50 g every day. Maximal time of exposure and observation was 12 weeks. The first tumors appeared in 2 male toads 4 weeks after the initiation of feeding. PMID- 8497380 TI - Aspirin shares a short-term effect, inhibition of pyruvate kinase activity with tumor-promoting agents, but fails to promote rat liver carcinogenesis. AB - Since aspirin was found to cause a persistent decrease in pyruvate kinase activity, which is a prominent characteristic of the hepatic promoters, the effect of aspirin on hepatic tumorigenesis in the rat has been studied. Male Wistar rats were initiated with a diet containing 0.06% 3'-methyl-4-dimethylamino azobenzene for 4 weeks. They were divided into 3 groups and each group was fed one of the following diets containing either 0, 0.5 or 1% aspirin. At the end of a 58-week experimental period, no differences were observed in the incidence of hepatic lesions and hepatocellular carcinomas among the groups. Thus, it was concluded that aspirin does not promote nor inhibit the postinitiation step of hepatic tumorigenesis in the rat. PMID- 8497381 TI - Bone marrow (reticuloendothelial system) scintigraphy for haematological follow up of radiochemotherapy-treated patients. AB - To assess the bone marrow capacity before a new treatment decision, 99mTc-human serum albumin bone marrow scintigraphy (with qualitative and quantitative evaluation) was performed in 32 patients with solid tumours or malignant lymphomas previously treated with radiochemotherapy. In the group with a normal bone marrow capacity, the blood counts were normal (14/16 cases) or became normal (2/16 cases) in the follow-up period, and the examined marrow samples exhibited normal haemopoiesis. In the group with a reduced bone marrow capacity, one or more blood counts were low in 14/16 cases. Decreased haemopoiesis was observed in only 4 of 8 examined marrow samples. The following conclusions were drawn. (1) A scintigraphically normal bone marrow capacity relates to normal haematological parameters, and therefore treatment plans could be decided on. (2) Although a reduced bone marrow capacity indicates pathological haematological conditions in the majority of cases, further studies are needed to evaluate its precise significance. (3) Application of this non-invasive, inexpensive, repeatable, non immunizing method is recommended before a therapeutic plan is decided on for patients at considerable haematological risk. PMID- 8497382 TI - Female thyroid cancer: the role of reproductive and hormonal factors in Switzerland. AB - We conducted a study on 91 women with thyroid cancer and 306 controls in hospital for acute nonneoplastic, non-hormone-related disorders in order to investigate the role of reproductive and hormonal factors in the etiology of epithelial thyroid cancer in the Canton of Vaud, Switzerland. Non-significant increases in cancer risk with an increasing number of full-term pregnancies (odds ratio, OR, after allowance for age and previous benign thyroid disease = 1.6, for > or = 3 vs. 0 full-term pregnancies, 95% confidence interval, CI: 0.7-3.6) and spontaneous abortions (OR = 2.0 for > or = 2 vs. 0 spontaneous abortions, 95% CI: 0.7-5.2) were seen. A significantly elevated OR (2.8, 95% CI: 1.1-7.2) was found in those women whose first pregnancy ended with an abortion. Whereas most other reproductive, menstrual and hormonal factors examined did not seem to affect the risk of thyroid cancer significantly, a clue emerged of an association between thyroid cancer and artificial menopause (OR = 6.3, for women who underwent artificial menopause vs. premenopausal women, 95% CI: 1.7-23.2). Although not necessarily causal, the relationship between the risk of epithelial thyroid cancer and the occurrence of spontaneous abortions and artificial menopause deserves attention in future studies, in the light of the high incidence of thyroid cancer in young and middle-aged women. PMID- 8497383 TI - A double-blind randomized crossover study to compare the antiemetic efficacy of 250 mg with 500 mg methylprednisolone succinate (Solu-Medrol) as a single intravenous dose in patients treated with noncisplatin chemotherapy. AB - A double-blind randomized crossover study was performed in 56 chemotherapy-naive patients, all receiving non-cisplatin-based chemotherapy, to compare the antiemetic effects of 2 doses of a single administration of methylprednisolone succinate (Solu-Medrol): 250 versus 500 mg. Among the 39 patients who satisfactorily completed both parts of the study, complete and major protection from emesis (0 and 1 emetic episode or only retching) was observed in 79% during the first course and in 69% during the second course. Treatment failure (> or = 6 episodes of vomiting) was observed in 18% during the first course and 21% during the second course. There was no significant difference between the two dose levels neither in terms of antiemetic protection nor in terms of the occurrence of side effects nor in patient preference. Most important side effects were facial flushing (45%), headache (22%) and facial edema (18%). It is concluded that, although a comparison with lower dosages cannot be made, within the dose range studied no clear dose-response relationship could be found. PMID- 8497384 TI - Phenotypic and functional analysis of expanded natural killer cell subpopulations in Hodgkin's disease patients treated with lymphoid irradiation. AB - We have evaluated the immunophenotype and function of presumptive NK cells taken from Hodgkin's disease patients before and after mantle/para-aortic lymphoid irradiation. We find that the lymphoid irradiation appears to induce a relatively stable, generalized expansion of the entire NK cell compartment rather than an increase in any specific NK cell subset. Flow cytometric cell sorting and functional NK cell assays based on immunophenotype demonstrate no significant changes in the phenotypic proportions of individual NK cell subsets and no significant changes in the lytic activity or cytotoxicity spectrum of these NK cells. These changes in the NK cell compartment may play a role in the long-term immunosuppression of these patients. PMID- 8497385 TI - [The effect of carotid endarterectomy on the reserve capacity of cerebral blood flow velocity]. AB - Cerebral blood flow velocity was measured by transcranial Doppler sonography at rest and during cerebral vasodilatation evoked with acetazolamide in 14 patients before and after carotid endarterectomy. Before surgery the vasoreactivity in the affected middle cerebral artery territories was reduced and abnormal (asymptomatic side: 35.9 +/- 25.6% [mean +/- SD; n = 14]; symptomatic side: 25.6 +/- 10.7%), but the difference between the two hemispheres was not significant however, vasoreactivity was normalized 5 days after surgery (asymptomatic side: 46.9 +/- 22.3% symptomatic side: 58.9 +/- 23%) (p < 0.001). The increase in cerebral reserve capacity and changes in Gosling's index of pulsatility correlated significantly in both hemispheres (p < 0.02). This findings indicate an improved perfusion reserve on the fifth day following carotid endarterectomy in patients with an internal carotid artery diameter reduction of at least 70%. PMID- 8497386 TI - [Long-term follow up study of children with celiac disease]. AB - 27 long term monitored coeliac children were assessed. The average length of follow-up was 6.4 years, the average age of the children was 11.5 years (ranging 6.3 to 20.1 years). Of the 11 boys and 16 girls 4 adolescents consume a normal diet, while another 2 are on semistrict diet, all 6 of them without any enteral symptoms. Out of the 15 children aged younger than 13 years 9 are on a strict diet. Semistrict diet has an impact on gliadin antibody levels respectively. Serum ferritin levels of those on a normal diet are significantly lower than those of the control group. Out of the 25 lactose breath tests 7 showed abnormal results, irrelevant both to the strictness of the diet and to gliadin antibody levels. In the view of weight and length percentiles there is no difference at present between those eating normal food and diet. Nevertheless, with regards to the risk of malignancy in coeliac disease the necessity of a strict diet must be stressed. In long term follow-up the levels of gliadin antibodies and of serum ferritin are of pathognostic importance. PMID- 8497387 TI - [Immunosuppressive effect of cyclophosphamide in experimental coagulase-negative staphylococcal infection]. AB - BALB/c mice were given 200 mg/kg cyclophosphamide intraperitoneally. Three days later, mice were infected intraperitoneally with Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus saprophyticus at 4 inocula ranging between 2 x and 20 x 10(8) CFU/ml suspended in dextran microcarrier solution. Controls were treated only with bacteria. Lethality rates and organ persistence of cocci were significantly higher, and more peritoneal abscesses and adhesions developed in the mice pretreated with cyclophosphamide than in the untreated controls, regardless of the species of Staphylococcus injected. Splenomegaly was also more pronounced indicating a probably enhanced compensatory reactivity of the immune system liberated from suppression 13 days after the administration of cyclophosphamide. Our results show that cyclophosphamide treatment increases the susceptibility of mice to infection by coagulase-negative staphylococci and it is also responsible for a more severe course of the diseases provoked. PMID- 8497388 TI - [Alternatives to minimally invasive cholecystectomy]. AB - Open endoscopic minimally invasive cholecystectomy procedures were developed as alternatives to laparoscopic as well as conventional cholecystectomy. The procedures: 1. Open endoscopic microsurgical removal of gallbladder (with or without laser) a 2-2.5 centimeters verticular median incision between the xiphoid and umbilicus. 118 operations with this technique has been performed. 2. Open endoscopic minimally invasive removal of gallbladder with 2.6-4 cms verticular median incision (63 patients) and 4.1-6 cms verticular median incision. Eighteen operations with this technique have been performed (7 choledocholithiasis, 4 accessory bile duct to the right liver lobe etc). Since 1990 we performed 200 consecutive open endoscopic minimally invasive cholecystectomy with no death and a morbidity rate of 1%. There were 161 women and 39 men (19 to 82 years). All gallbladder diseased patients are candidates for this procedures including patients with acute cholecystitis, empyema of the gallbladder, choledocholithiasis, large gallstones or previous abdominal surgery. These procedures are designed as safe, less expensive alternatives to laparoscopic or conventional cholecystectomy. PMID- 8497389 TI - [Congenital macrodactyly]. AB - Macrodactyly is a rare congenital anomaly affecting the limbs. A case--treated by author at Al Thawra Hospital Sanaa, Yemen Arab Republic--is presented with a brief review of the literature and the difficulties of the treatment. PMID- 8497390 TI - [Elizabeth, queen of Hungary, memorialized on medals relating to medicine]. PMID- 8497391 TI - [Sexual aberrations and mental competence in the 2nd half of the 19th century]. PMID- 8497392 TI - [Prevention of thrombosis in surgery of the extremities. Physical methods in thrombosis prevention]. AB - Physical therapy procedures for the prophylaxis of thrombosis are part of basic medical therapy. Their effect has been documented by numerous individual observations, even though no prospective studies are available. Since the inconvenience to the patient is minor, they should be implemented in all surgical patients. In the case of patients at risk of thrombosis such as in orthopedic surgery, the effect of such procedures is not sufficient. In this case physical therapy procedures can only supplement the medical prophylaxis of thrombosis. The effectiveness of technically more complex physical procedures has been documented in small studies, but due to the high technical and personnel costs, the application is restricted. PMID- 8497393 TI - [Venous thrombosis following severe multiple trauma]. AB - The incidence of thromboembolic complications in patients with multiple injuries was reviewed as well with respect to our own prospective investigation (141 patients with a mean injury severity score of 37 points). The rate of deep venous thrombosis (DVT) in severely injured patients is reported to vary from 20 to 90% if invasive diagnostic procedures are used, whereas the rate of clinically relevant manifestations of DVT seems to be much lower. Although 96% of the patient population in our study were thought to be at high risk of having DVT (applying generally accepted risk factors), only 1.4% of the subjects actually developed clinically relevant DVT. The analysis of several parameters of the coagulation and fibrinolytic systems (platelet count, prothrombin time, partial thromboplastin time, antithrombin III, prothrombin, plasminogen, tissue plasminogen-activator and its inhibitor) showed simultaneous activation of both systems in these severely injured patients. Thus, increased coagulation seems to be counteracted by increased fibrinolysis. In addition, fluid resuscitation with crystalloid and colloid infusions in the prehospital period (1970 ml and 573 ml, respectively) can be viewed as early prophylaxis of thromboembolic complications. Thus, the low DVT rate in a high-risk patient group with multiple injuries might be at least partially explained. PMID- 8497394 TI - [Prevention of thrombosis in ambulatory patients]. AB - In surgical outpatients who required immobilization with a plaster cast because of injury to the lower limb a deep vein thrombosis occurred in 14%. General thromboprophylaxis seems advisable for surgical outpatients and depends on the severity of trauma and thrombosis risk factors. In a study of 97 patients who received a daily subcutaneous injection of heparin fragment calcium throughout their cast period, only one patient with a deep vein thrombosis was seen. PMID- 8497395 TI - [Venous thrombosis--clinical aspects and diagnosis]. AB - Physical examination is in most cases not specific or sensitive enough to diagnose venous thrombosis. Only in rare cases is it possible to diagnose thrombosis by history and examination alone. However, when the case history indicates that risk factors are present, one must suspect thrombosis even if the clinical findings are uncharacteristic. In this situation the diagnosis must be verified by additional technical examinations. PMID- 8497396 TI - [Technological diagnosis of venous thrombosis]. AB - The bedside diagnosis of deep venous thrombosis is not accurate enough to implement invasive therapy, e.g., systemic administration of thrombolytic agents, so the diagnosis must be established by independent diagnostic means. The most useful diagnostic tests available include Doppler ultrasound, duplex sonography, color duplex sonography, and contrast venography. The common femoral vein and popliteal vein can be examined easily with a Doppler ultrasound probe. Reduced blood flow due to major venous thrombosis proximal or distal to the probe, qualitative blood flow and flow direction are all detectable. Duplex sonography allows imaging of thrombosed areas and provides structural information on thrombi and the attachment sites to the endothelium. These noninvasive methods are insensitive to thrombosis in the lower leg. Color duplex sonography in addition provides diagnostic information about the quantitative blood flow and simplifies the diagnostic procedure. If these tests are not available or the findings are equivocal, contrast venography is performed, which is the most sensitive and reliable test for confirming or excluding deep venous thrombosis. PMID- 8497397 TI - [Treatment of venous thrombosis]. AB - In the treatment of deep vein thrombosis (DVT), a rapid clinical diagnosis supported by the appropriate equipment, the age of the patient, and the extent of the thrombosis are the major determinants of successful therapy. Active and conservative treatment should be aimed at the prevention of pulmonary embolisms, rethrombosis and elimination of the thrombus, while preserving venous valvular function, which in turn is essential to avoid the development of post-thrombotic syndrome. The treatment of acute DVT remains controversial. For this reason the indication, treatment, and recently published results of thrombectomy, thrombolysis, and the possibilities for preventing DVT are discussed. PMID- 8497398 TI - [Forensic aspects of deep venous thrombosis of the leg]. AB - Enough attention is still not being given to deep venous thrombosis in the leg- at least on an outpatient basis--and it is also underestimated. Immobilizing bandages are associated with the most danger. Medical prophylaxis of thrombosis is indicated in order to protect patients from injury and to accommodate forensic requirements. The number of malpractice suits is considerable and it is still going on. The advantages and disadvantages of immobilization bandages must be explained to the patients. If deep venous thrombosis is recognized and treated too late, the consequences are irreversible. PMID- 8497399 TI - [Observations on pathophysiology and pathogenesis of venous thrombosis]. AB - Even today, Virchow's triad is still a useful method for describing the circumstances under which thrombosis can occur. To investigate the underlying pathophysiological principles, however, the methods must differentiate more clearly. Only recently, the complicated interactions of blood coagulation and fibrinolysis have been described. Although detailed determinations of markers of activated coagulation and fibrinolysis can be performed, it has not been possible to achieve a reliable screening method to indicate the individual patient's risk. Alterations in the endothelial cells seem to play a key role in thrombogenesis. The clinician's interest in thrombosis research is based on several open or insufficiently answered questions, such as why thrombosis can occur in veins for away from the site of the operation, whether reliable and simple screening methods can be established in order to determine the patient's risk constellation, and how the methods of preventing thrombosis and administering therapy can be improved. PMID- 8497400 TI - [Psychiatry in Scandinavia]. PMID- 8497401 TI - [What do we know about "white coat" hypertension?]. PMID- 8497402 TI - [Schizophrenia Project in Abo. Psychotherapy-oriented broad-based mental health care]. AB - The concept of need-related care for schizophrenia patients, evolved in Abo during the 1980s, consists in a flexible form of psychotherapy oriented care, which in its planning and execution is tailored to meet varying individual needs. It is based both on family and individual therapy and therapeutic groups, drugs being used as support. The results have been promising and it has been possible to reduce hospitalisation. PMID- 8497403 TI - [Mental illness in patients in primary health care. A Scandinavian multicenter study]. AB - In a Nordic multicentre study of psychiatric illness in primary care, patients in four health districts were screened for psychiatric illness. General practitioners' ratings of psychiatric illness and patients' ratings of psychosocial problems were also included. The patients' utilisation of care and health insurance facilities was reviewed. A random subsample of patients were invited to a semi-structured diagnostic interview with a psychiatrist. Results from the Swedish part of the study showed about 1/3 of the 724 patients investigated to be probable psychiatric cases, while 1/5 were psychiatric cases in need of treatment. The psychiatric cases were characterised by a preponderance of divorced, unemployed women. At 1-year follow up, the utilisation rate of care and health insurance facilities among psychiatric cases was found to be higher than for nonpsychiatric cases. PMID- 8497404 TI - [New Swedish foundation for psychiatric research]. AB - Psychiatric research in the five Nordic countries has yielded a substantial body of work during recent years-e.g., on Alzheimer's disease, schizophrenia and neurotransmitters. Owing to their geographic position and the reliability of their demographic records, the Nordic countries are uniquely suited to epidemiological studies-e.g., of mental disorders over time. Research spans both the fields of biological and clinical community psychiatry in all five countries, though the emphasis varies somewhat: the focus in Sweden and Denmark being more on biological psychiatry, while in Norway and Finland it is more on community, adolescent, and emergency psychiatry. PMID- 8497405 TI - [Contributions within Danish psychiatric research]. PMID- 8497406 TI - [Psychiatric research in Iceland]. PMID- 8497407 TI - [Norway's contribution to psychiatric research]. PMID- 8497408 TI - [Between nature and culture. Psychology's contribution to health science and practice]. PMID- 8497409 TI - [Message from Lyme]. AB - The background to the discovery of Lyme disease teaches a salutary lesson. The symptoms and signs of this disease had been observed by doctors for a century, particularly in the Scandinavian countries, without anybody being able to draw the right conclusions. The first patients were identified in the USA by their relatives or by themselves. Recognition of their plight by the medical profession was chiefly due to the patients' tenacity. We must remember to pay attention to what patients tell us; they may often be right, even when they seem to be wrong. Where fact and theory are incompatible, it is theory, not fact, that needs to be amended. In all likelihood, we all from time to time observe disorders in our patients that are inconsistent with established scientific models, but which we nevertheless attempt to squeeze into these models. Such an approach is not uncommon in the history of medicine. The message from Lyme calls for humility and reflexion. PMID- 8497410 TI - [Scandinavian articles and journals in the Science Citation Index. Farewell to Scandinavianism]. PMID- 8497411 TI - [Goal-describing guidance tool in physicians' continuing education]. PMID- 8497412 TI - [Public health administration in Estonia]. AB - All parts of the former Soviet Union experience enormous problems in their clinical health sectors. However, reforms of public health administrations are also needed. This is illustrated, using Estonia as an example, based on the author's function as a consultant to the Estonian Ministry of Health. At the local level, expertise should be concentrated in a few regional public health centres with strong laboratory support. Centrally, the new Ministry of Social Affairs must play a strong role to make sure that the traditional system is adapted. "Organization development" and postgraduate training should be useful instruments in this process. Support from the Nordic countries is encouraged. PMID- 8497413 TI - Reader calls for healthcare organizations to severe tobacco industry's roots. PMID- 8497414 TI - Use of thalidomide for CGVHD defended. PMID- 8497415 TI - A systematic evaluation of the "I Can Cope" program using a national sample. AB - "I Can Cope" (ICC) is an educational program that provides resources that help people with cancer, their families, and their friends to cope more adequately with the disease and its consequences. Although the American Cancer Society (ACS) has offered this program since 1979, ICC never has been evaluated nationally. ACS developed the ICC Revision Work Group in 1990. This work group initiated a national evaluation of ICC to provide data in eight areas: demographics, class format, course objectives, course content, audiovisual and instructional materials, facilitator training, program implementation, and program evaluation. During 1991, data were collected from 219 facilitators, 241 ACS staff members, and 973 ICC participants in 49 states. Revision of the ICC program using the results of this evaluation currently is underway. PMID- 8497416 TI - Influence of age on problems experienced by patients with lung cancer undergoing radiation therapy. AB - The purpose of this prospective, longitudinal study was to determine if patients with lung cancer who are 65 years of age or older experience problems differently than do patients younger than age 65 during and following radiation treatment. The moderator and outcome variables selected for study were recognized attendant problems that may develop during lung cancer treatment and that may influence the treatment regimen and response. No statistically significant differences were found between patients age 65 or older and those younger than age 65 on caloric intake, adequacy of energy intake, total radiation dose, concurrent illnesses, and social support at any of four data-collection periods. Similarly, there were no significant differences on weight, body mass index, and multidimensional functional status. The relationship between the social support subscales and functional status measures for the 65-or-older group suggested that those subjects with lower social support perceived themselves to have better functional status. There was no relationship between social support and two functional status measures for the under-65 group. The significant relationships between social support and the overall health rating were in opposite directions for the two age groups. The results suggest that chronologic age alone may not be a sufficient criterion to determine therapeutic regimen or to suggest that unique problems may result. PMID- 8497417 TI - The lung cancer experience: comparison of variables and findings across three studies. PMID- 8497418 TI - Vena cava filters: a nursing perspective. AB - Healthcare professionals increasingly are using vena cava filters to prevent pulmonary emboli (PE) in patients with cancer. Patients with cancer are predisposed to developing thrombosis and subsequent PE for a variety of reasons. These patients commonly have contraindications to anticoagulant therapy because of their disease or cancer treatment; therefore, vena cava filters are an appealing option for managing potential emboli. This article describes the etiologies of thrombosis in patients with cancer; problems associated with conventional anticoagulant therapy; vena cava filters and placement procedures; complications associated with filter placement; and related nursing implications pre- and postinsertion and during long-term follow-up. PMID- 8497419 TI - Women's expectations about seeking care for breast cancer symptoms. AB - Expectations about a particular health behavior can influence whether a person engages in that behavior. This study was conducted to identify women's expectations about seeking or not seeking prompt care for breast cancer symptoms. Guided by theory, interview questions elicited expected outcomes, advantages, and disadvantages of promptly seeking care or of adopting a "wait and see" approach. Forty participants between the ages of 26 and 73 who had no history of breast cancer were interviewed. Responses were categorized according to common themes. Outcomes and advantages of seeking care included receiving a diagnosis or treatment, as well as reassurance and knowledge; disadvantages included financial costs and undesirable interactions with physicians. Outcomes and disadvantages of waiting included a worsened condition and a lower chance of survival; advantages included financial savings and possible resolution of the condition. PMID- 8497420 TI - Chemotherapy: thoughts and images of patients with cancer. AB - Cognitive therapists believe that an individual's emotional reaction to a stressful situation is influenced by his or her perception of that situation. This article reports the findings of a cross-sectional survey comparing thought and image patterns in patients with cancer receiving first-time chemotherapy with patients receiving subsequent treatments. The 30 patients in each sample listed their thoughts and images before, during, and after chemotherapy. In both samples, a higher percentage of positively rated self-talk units were expressed; most negative thoughts took place before the chemotherapy. Qualitative content analysis revealed that, in first-time chemotherapy recipients, the most frequently reported thought categories were questions and concerns about chemotherapy, positive evaluations of treatment, positive coping, and negative feelings. In the subsequent-treatment recipients, they were positive coping, physiologic reactions, hope, and positive evaluations of treatment. Nursing implications and future research directions also are discussed. PMID- 8497421 TI - Outcome of a quality assurance review: development of a documentation tool for chemotherapy administration. AB - Nursing quality assurance (QA) is a systematic evaluation program to promote quality nursing practice. As part of a QA project, hospital records of 28 patients who received chemotherapy were reviewed to determine whether nursing documentation of chemotherapy administration complied with the standards of oncology nursing practice. Because the audit identified some deficiencies in documentation, a flow sheet was developed to resolve problem areas. A retrospective audit of 18 charts was conducted six months after the new flow sheet was initiated. The audit revealed 100% compliance for each key indicator that was evaluated. This article describes the QA process that led to the development and evaluation of the new flow sheet. PMID- 8497422 TI - Hearing aid assists nurses with patient education. PMID- 8497423 TI - Elderly patients tolerate chemotherapy well. PMID- 8497424 TI - Sewing caddy aids in medication administration. PMID- 8497425 TI - Taking more time enhances care of the elderly. PMID- 8497426 TI - Tips offered for teaching elderly patients with cancer. PMID- 8497427 TI - Ultrastructural study of the ventral lobe of the prostate of rats submitted to experimental chronic alcoholism. AB - The effects of chronic alcohol ingestion on the ventral lobe of the prostate were studied in rats (Rattus norvegicus). Ultrastructural observations on the epithelial cells of the ventral lobe of the prostate showed irregularly shaped nuclei with deep infoldings, dilated RER cisternae, and a small number of microvilli covering the cell surface. After 90 and 135 days of alcohol treatment, the epithelial cells showed signs of degeneration. PMID- 8497428 TI - Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. AB - The effect of the isoflavones, genistein, daidzein, and biochanin A on the growth of the LNCaP and DU-145 human prostate cancer cell lines has been examined. Genistein and biochanin A, but not daidzein, inhibit both serum and EGF stimulated growth of LNCaP and DU-145 cells (IC50 values from 8.0 to 27 micrograms/ml for serum and 4.3 to 15 micrograms/ml for EGF), but have no significant effect of the EGF receptor tyrosine autophosphorylation. In contrast, tyrphostin 25, a specific EGF receptor tyrosine kinase inhibitor, inhibits EGF stimulated growth and EGF receptor tyrosine autophosphorylation in these whole cells, but does not inhibit serum-stimulated growth. These data suggest that the mechanism of action of genistein and biochanin A does not depend on inhibition of EGF receptor tyrosine autophosphorylation, but on a more distal event in the EGF receptor-mediated signal transduction cascade. PMID- 8497429 TI - Beta-microseminoprotein immunoreactivity as a new prognostic indicator of prostatic carcinoma. AB - Human beta-microseminoprotein (beta-MSP), isolated from seminal plasma, is one of the proteins secreted by the prostate gland. To determine whether the beta-MSP immunoreactivity can be a prognostic indicator of prostatic carcinoma, the beta MSP immunohistochemical distribution has been examined in needle biopsy specimens taken from 96 patients with prostatic carcinoma. Although no significant correlation was found between the beta-MSP immunoreactivity and the histological grade (Gleason score), patients with a positive beta-MSP expression had a significantly better prognosis than those with a negative beta-MSP expression (P = 0.01). Further, a multivariate analysis of six possible parameters (age, clinical stage, histological grade, serum prostatic acid phosphatase, beta-MSP immunoreactivity, and the type of initial treatment) has shown the difference in the beta-MSP immunoreactivity to be a significant, independent, prognostic indicator of prostatic carcinoma (P = 0.04). PMID- 8497430 TI - Paediatrics--Part I. PMID- 8497431 TI - Quality of life of hirsute women. AB - Hirsutism is recognized to cause profound distress in affected women, due to cosmetic and psychosexual implications. It was evaluated in the present study by methods found to be valid and reliable in psychosomatic research. Fifty women with hirsutism belonging to the spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome, after complete medical work-up, underwent the same psychometric evaluation as 50 healthy non-hirsute women, matched for sociodemographic variables. Hirsute women had a Ferriman and Gallwey score ranging from 8 to 19. Psychometric evaluation for quality of life was carried out by the following methods: (a) Kellner's Brief Problem List, a 12 item self-rating list of psychosocial problems; (b) Kellner's Symptom Rating Test (SRT), a 46 item self-rating scale that yields a total score of distress as well as six subscales (anxiety, depression, somatic symptoms, anger-hostility, cognitive and psychotic symptoms); and (c) Marks' Social Situations Questionnaire (SSQ), a 30 item self rating scale concerned with social phobia. Patients with hirsutism displayed significantly higher social fears at the SSQ than controls (P < 0.01). They also showed more anxiety (P < 0.01) and psychotic symptoms (P < 0.01) at the SRT, whereas there were no significant differences in depression, somatization, anger hostility and cognitive symptoms. These results suggest that the complex management of hirsute women, in addition to pharmacological and/or cosmetic measures, may require specific psychotherapy. PMID- 8497432 TI - Use of thrombolysis for acute myocardial infarction by general practitioners. AB - The early administration of thrombolytic agents significantly reduces mortality following a myocardial infarct and ideally they could be given by general practitioners when the patient is first seen. However, the diagnosis of myocardial infarction in the early stages can be very difficult especially if an electrocardiogram is not available. This may limit the use of thrombolytic drugs by general practitioners. We assessed the accuracy of diagnosis in general practice by asking general practitioners referring patients with chest pain, the likelihood that the event was due to a myocardial infarction and if they would use thrombolysis if it were available. Diagnostic accuracy and appropriate use of thrombolysis was analysed retrospectively, comparing the general practitioner with the admitting hospital doctor. One hundred consecutive patients were studied. The general practitioners accurately diagnosed myocardial infarctions in approximately 45% of cases and would have given thrombolysis inappropriately on 67% of occasions mainly because the final diagnosis in most of these patients was unstable angina rather than infarction. The hospital doctors administered streptokinase inappropriately to 33% of the patients and four had complications during treatment. Of those patients receiving thrombolysis, the average time delay from the general practitioner referring the patient to hospital to the patient being treated was 107 minutes. This study confirms that the diagnosis of myocardial infarction in the early stages is difficult and that thrombolytic therapy may be given inappropriately (mainly to patients with unstable angina). We conclude that until the accuracy of diagnosis of myocardial infarction can be improved in general practice it would seem inappropriate for thrombolysis to be given in the community at the moment. PMID- 8497433 TI - Age-related differences in simultaneous interarm blood pressure measurements. AB - Simultaneous noninvasive blood pressure measurement were recorded bilaterally in 40 young and 40 elderly subjects. Overall interarm blood pressure (BP) differences for the elderly and young groups were similar, the absolute interarm differences being for systolic blood pressure (SBP) elderly: 4.2 mmHg (95% CI 3.1 5.3 mmHg); young 3.3 mmHg(2.6-4.1 mmHg); diastolic blood pressure (DBP) elderly 3.6 mmHg(2.8-4.4 mmHg), young 2.7 mmHg(2.0-3.3 mmHg). However, the range of interarm BP differences was wide. Four (10%) of the elderly had an interarm SBP difference > 10 mmHg compared to one (3%) of the young group. Interarm DBP differences > 8 mmHg were found in three (8%) of the elderly and in none of the young group. Although age does not affect mean interarm BP differences, clinically important interarm BP differences exist in both young and elderly subjects. Blood pressure should be measured in both arms of all patients at initial assessment to avoid potential problems with misclassification of blood pressure status. PMID- 8497434 TI - The impact of a short course of three lipid lowering drugs on fat oxidation during exercise in healthy volunteers. AB - We examined the impact of three lipid lowering drugs on fat oxidation during a 120 minute treadmill walk, at an exercise intensity of 50% maximal oxygen uptake (VO2 max). Subjects (N = 24) were healthy male volunteers with normal serum chemistry, assigned to three groups (n = 8). Group A received simvastatin 20 mg twice daily, Group B received gemfibrozil 600 mg twice daily, Group C received acipimox 600 mg twice daily. Each subject performed two 120 minute walks, once with drug, and once with placebo (4 days treatment plus a final dose on the morning of the exercise trial). Treatment order was reversed for half of each group. Compared to placebo, simvastatin treatment, had no impact on fat oxidation (40.9 +/- 8.6% vs 40.9 +/- 9.7%), or on plasma concentration of free fatty acids (FFA), glycerol or glucose. Treatment with gemfibrozil, showed lower fat oxidation (32.3 +/- 13.9% vs 39.7 +/- 7.9%), and lower plasma concentrations of FFA and glycerol, but differences did not reach significance at the 0.05 level. Acipimox treatment, produced significantly lower fat oxidation (36.9 +/- 12.8% vs 50.2 +/- 16.1%, P = 0.011), and lower plasma concentrations of FFA and glycerol (P = < 0.0001 and P = < 0.0001, respectively). Plasma glucose showed a trend toward lower values with acipimox (P = 0.088). These data demonstrate that selective lipid lowering drugs can reduce fat availability for exercise metabolism, placing increased demands on carbohydrates which may reduce exercise tolerance. PMID- 8497435 TI - Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin dependent diabetes mellitus (NIDDM). AB - A total of 412 Hong Kong Chinese diabetic patients were studied on at least two occasions 8-16 weeks apart. Although 28% were insulin-treated, only 3.6% had insulin-dependent diabetes (IDDM). In the remaining 397 patients with non-insulin dependent diabetes (NIDDM), the mean (s.d.) body mass index (BMI) was 24.4 +/- 3.2 kg/m2 in females and 24.2 +/- 3.2 kg/m2 in males. Obesity was present in 17% of males (BMI > 27 kg/m2) and 40% of females (BMI > 25 kg/m2). Established hypertension was present in 49%. Abnormal albuminuria, defined as a mean urinary albumin/creatinine (UA/Cr) ratio greater than 5.4 mg/mmol based on two random spot urine samples, was present in 47%. On stepwise multiple regression analysis, UA/Cr ratio (R2 = 0.34, F = 65.4, P < 0.001) showed significant associations with systolic blood pressure (standardized regression coefficient beta = 0.40, P < 0.001), plasma creatinine concentration (beta = 0.27, P < 0.001) and glycosylated haemoglobin (beta = 0.20, P < 0.001). While the prevalence of hypertension increased with increasing severity of proteinuria, 40% of normoalbuminuric patients had hypertension. Among patients diagnosed before the age of 35 (n = 67), 52% were insulin-treated although only 10% were insulin-dependent. Among these NIDDM patients of young onset (n = 59), obesity was present in 25% of males and 56% of females. Overall, 18% of these patients had a blood pressure greater than 140/90 mmHg and 27% had abnormal albuminuria. In Hong Kong Chinese, diabetes mellitus is predominantly non-insulin-dependent even in the young. Obesity is more prevalent among females. Abnormal albuminuria is relatively common and is closely associated with hypertension and glycaemic control. In the light of increasing prevalence of diabetes among overseas Chinese, our findings may have important implications in the management of Chinese diabetic patients. PMID- 8497436 TI - Asymptomatic acute pyelonephritis as a cause of acute renal failure in the elderly. AB - Urinary tract infections in the elderly are common, often asymptomatic and usually benign. We report three patients who presented with acute renal failure due to acute pyelonephritis in the absence of clinical findings of infection or urinary tract obstruction. Blood and urine cultures grew Escherichia coli in two of the patients and in two patients renal biopsy confirmed acute pyogenic pyelonephritis. Antimicrobial therapy and haemodialysis led to improvement, though one patient subsequently died from an unrelated cause. We suggest that acute bacterial pyelonephritis should be considered as a cause of acute renal failure in the elderly. Clinical features of infection may be absent despite bacteraemia. Prompt diagnosis and intervention may avoid chronic renal failure in a group that has a less favourable outcome with long-term dialysis. PMID- 8497437 TI - Spontaneous rupture of the oesophagus (Boerhaave's syndrome). AB - Five cases of spontaneous rupture of the oesophagus are reported. All cases had surgery within 12 hours, and all survived, illustrating the value of early diagnosis in this rare condition. None had their diagnosis made before admission to the hospital. Myocardial infarction is the commonest misdiagnosis and frequently results in delayed treatment. We believe that a simple direct question to enquire of the patient whether or not vomiting preceded the onset of the severe pain would significantly reduce the rate of misdiagnosis. PMID- 8497438 TI - Behavioural approaches to anxiety disorders. AB - Powerful behavioural treatments for many patients with anxiety disorders have been widely available since the 1970s. Despite this, the majority of such patients have continued to be treated with psychotrophic drugs. Recent litigation against the manufacturers of benzodiazepine drugs has made the public increasingly concerned about the prescription of anxiolytic agents. In parallel with the fall in popularity of drug treatment, advances have been made which increase the availability and applicability of behavioural treatments for these patients. This paper examines the impact of the development of self-exposure and cognitive methods on a number of common anxiety syndromes. Clinical examples of self-exposure are given to demonstrate the simplicity of the technique. PMID- 8497439 TI - A patient with recurrent hypothermia associated with thrombocytopenia. AB - A 69 year old woman had 13 hospital admissions because of hypothermia attributed to self-neglect. On each occasion she was found to be thrombocytopenic, and the platelet count always returned to normal with rewarming. The case records of all patients admitted to the Victoria Infirmary between 1986 and 1990 with a primary diagnosis of hypothermia were reviewed. Two other patients of the 75 assessed were found to have had thrombocytopenia linked to hypothermia, but neither showed a recurrent relationship. PMID- 8497440 TI - Thrombotic thrombocytopenic purpura associated with pregnancy in two sisters. AB - Two sisters suffered from thrombotic thrombocytopenic purpura late in their first pregnancies. HLA typing of the patients and their immediate family members demonstrated no obvious relationship. Hereditary aspects, association with pregnancy, prognosis and management of pregnant women with TTP are discussed. PMID- 8497441 TI - Ischaemic complications of graduated compression stockings in the treatment of deep venous thrombosis. AB - Graduated compression stockings are frequently used in the prevention of deep venous thrombosis and the treatment of venous insufficiency. Two patients are discussed who sustained ischaemic complications after application of graduated compression stockings. Review of the literature demonstrates that low cutaneous pressures significantly decrease local blood flow and that the amount of pressure exerted by graduated compression stockings increases significantly with increases in leg girth. Ischaemic complications associated with the use of these stockings also appears to be more common than previously thought and any policy of routine prescription to patients should be questioned. PMID- 8497442 TI - Portal vein thrombosis due to Candida albicans associated with hepatic cirrhosis. AB - A case of portal vein thrombosis due to Candida albicans in a patient with alcoholic hepatic cirrhosis in the absence of hepatocarcinoma is described. Infection is a known cause of portal vein thrombosis but thrombosis by Candida albicans has not to our knowledge been previously reported. PMID- 8497443 TI - Keloid of the penis after circumcision. PMID- 8497444 TI - Resolution of danazol-induced cholestasis with S-adenosylmethionine. AB - In a case of danazol-induced cholestasis, the anti-cholestatic agent S adenosylmethionine was given intravenously for 3 weeks and then orally for 6 weeks. This was well tolerated and led to prompt resolution of both jaundice and associated renal impairment. PMID- 8497445 TI - Hallucinations as an adverse effect of angiotensin converting enzyme inhibition. PMID- 8497446 TI - Suspicious mind: the association between Streptococcus bovis endocarditis and carcinoma of the colon. PMID- 8497447 TI - Successful treatment by gonadotrophins of a patient with genetic haemochromatosis and infertility. PMID- 8497448 TI - Aspirin and risk of fatal colon cancer. PMID- 8497449 TI - Acute epiglottitis in adults. PMID- 8497450 TI - Pharyngeal pouch presenting as dysphagia after a stroke. PMID- 8497451 TI - Spontaneous haemorrhage into a pituitary tumour after streptokinase therapy. PMID- 8497452 TI - Laboratory testing and biochemical analysis of hyperlipidaemias. AB - In establishing the accuracy of cholesterol measurements, attention must be devoted to aspects of the pre-analytical phase, such as preparation of the patient and type of specimen used. Cholesterol measurement is most accurately performed by means of a gas chromatographic-mass spectrometric procedure, while most clinical laboratories use an enzymatic method. Lipoprotein fractionation techniques vary, from simple precipitation used to determine HDL cholesterol to ultracentrifugation. The most widely used procedure for estimating LDL cholesterol depends on the use of the Friedewald formula. Methods for measuring triglycerides are not as well developed as those for cholesterol and no reference method has yet been established. However, there is recent evidence that home monitoring of triglyceride levels in diabetic subjects using a Reflotron can encourage a reduction in triglyceride levels. This review concludes with a discussion of the measurement of apolipoproteins and the more complex investigation of specific hyperlipidaemias. It seems that techniques from molecular biology, such as the use of the polymerase chain reaction, will find increasing use in the assessment of hyperlipidaemias in the future. PMID- 8497453 TI - Diabetes, hypertension and hyperlipidaemia. AB - The predominant cause of death among diabetic patients in populations with high cholesterol levels is coronary heart disease. This effect is related to diet and both insulin dependent and non-dependent diabetes are characterized by an increase in circulating very low density lipoprotein (VLDL). Insulin deficiency or resistance accelerates the release of VLDL from the liver. However, the susceptibility to vascular disease seen among diabetics may be a particular function of their raised levels of intermediate density lipoproteins (IDL) produced when VLDL is metabolised to low density lipoprotein. The concept of hyperinsulinaemia is not helpful in explaining the diabetic patient's disturbed metabolism and is a source of confusion. The major therapeutic task in non insulin-dependent diabetes is often to reduce the patient's weight and thus to reduce insulin resistance. In patients with coronary heart disease, this should be fully investigated at least as promptly as in non-diabetic people. Lipid lowering drugs, and particularly the fibrates, are suitable for treating diabetic patients since they lower both cholesterol and triglycerides and raise HDL. There is much more controversy about the ideal choice of antihypertensive agents, particularly for patients with only moderate increases in blood pressure. Both thiazides and beta-blockers disturb the lipid profile most markedly in many patients with diabetes or primary hyperlipidaemia. Current evidence suggests that many patients with hypertension, but no other cardiovascular risk factors, derive no benefit from receiving antihypertensive therapy. As in the management of hypercholesterolaemia, the decision to introduce drug therapy should not be determined by the blood pressure reading alone, but should take account of the whole patient risk. The combination of even "mild" hypertension with diabetes or hyperlipidaemia demands greater therapeutic activity and then there is a case for the use of antihypertensive agents which do not adversely influence the lipid profile. PMID- 8497454 TI - Cost-effectiveness of hypolipidaemic drugs. AB - Prevention of coronary heart disease involves intervention at both the population and the individual level. These procedures are complementary. Opportunistic screening and management of hypercholesterolaemia in general practice is an efficient procedure. Calculations show that the cost of each quality adjusted year of life saved by such an opportunistic approach compares favourably with that of other approaches to coronary heart disease treatment as well as other coronary prevention programmes. Cost-effectiveness is greater in those with existing coronary heart disease but lower for the treatment of younger patients. This presentation considers the relative costs of drug treatment in relation to cholesterol reduction, but emphasizes that high density lipoprotein cholesterol and triglyceride levels must also be considered. Cholesterol management should form part of a multiple risk factor assessment with priority for those at high overall risk. Active dietary intervention should be offered to all patients, with drug treatment reserved for a small minority. The choice of drug treatment should depend on the required cholesterol reduction, the pattern of hyperlipidaemia and the cost of treatment. PMID- 8497455 TI - Mechanism of action of fibrates. AB - Fibrates are effective in hypertriglyceridaemia and hypercholesterolaemia. They affect both triglyceride-rich and cholesterol-rich particles and have at least four separate modes of action. These include limitation of substrate availability for triglyceride synthesis in the liver; promotion of the action of lipoprotein lipase; modulation of low density lipoprotein (LDL) receptor/ligand interaction and stimulation of reverse cholesterol transport. Studies of LDL metabolism suggest the existence of two separate catabolic pathways involving the LDL receptor and scavenger mechanism(s). The former route is anti-atherogenic; the latter pro-atherogenic. At low triglyceride levels, the fractional clearance of LDL by the receptor is high. The action of fibrates is to promote the secretion of LDL which is cleared by a receptor-mediated mechanism. Catabolism of this fraction increases from 40% of the plasma pool per day in untreated to 60% per day in treated subjects. By activating lipoprotein lipase, fibrates also reduce the amount of small dense LDL, the fraction which is most likely to generate peroxidation products. Hence, fibrates stimulate LDL receptor-dependent clearance mechanisms and reduce the amount of LDL available for oxidation. PMID- 8497456 TI - Ciprofibrate--a profile. AB - The cornerstone of management in hyperlipidaemia is dietary and lifestyle therapy. Nonetheless, a proportion of patients will require drug therapy. Of the currently available choices, statins are of obvious value for raised cholesterol and low dose resins have a place in treating moderate hypercholesterolaemia. There is also an important role for the fibrates, particularly for modifying the hypertriglyceridaemic state and hence influencing low density lipoprotein (LDL) metabolism. Ciprofibrate is a compound newly introduced into the United Kingdom which shares many pharmacokinetic properties with other fibrates. Time to maximum serum concentration is about one hour and the long elimination half life (80 hours) permits once daily dosing. After a 12 week treatment period in Type II patients, LDL cholesterol was reduced by 24%. More recent work has shown a fall among Type IIa patients of 29% in LDL cholesterol with an increase in HDL cholesterol when ciprofibrate was given at 200 mg/day. A triglyceride reduction of 42% was recorded in Type IIb patients. Favourable effects have been described at 5 years of follow up for patients with Type IIa, Type IIb and Type IV patterns. Effects on clotting parameters are favourable and there is no significant long-term effect on biliary cholesterol saturation. In addition, no structural changes were observed in a small number of biopsies from treated patient liver. Side effects and contraindications are as for other fibrates. Ciprofibrate seems to be a valuable addition to drug therapy for the management of a variety of dyslipidaemias. PMID- 8497457 TI - Lipids as a coronary risk factor: analysis of hyperlipidaemias. AB - Despite difficulties with epidemiological data, there is little doubt that triglyceride-rich lipoproteins are important factors in the induction of human atherogenesis, although the mechanisms remain elusive. A statistical association exists between small chylomicron remnant concentrations and fasting triglyceride levels and a stronger link is found between the larger chylomicron remnants and larger very low density lipoproteins. The link between concentrations of chylomicron remnants and disease progression is not explained by any relationship to the high density lipoprotein system but rather reflects the direct atherogenic action of the small chylomicron remnants themselves. Dense low density lipoprotein (LDL) triglyceride concentration seems to be more strongly correlated with disease severity in young post-infarction patients than LDL cholesterol concentration. There has been much recent interest in the process of LDL oxidation which re-routes LDL from normal receptors to the scavenger receptor pathway. In this regard, it was interesting to find a strong inverse correlation between low LDL vitamin E content and arterial stenosis. The relationship between dense LDL and coronary disease may depend on several different pathways all of which implicate the triglyceride-rich lipoproteins in the pathogenesis of coronary artery disease. PMID- 8497458 TI - [Sleep-related respiratory disorders: early detection and follow-up by close patient contact]. AB - Sleep apnoea (SA) ist a challenge to clinical research, since it occurs in up to 10% of the male professionally active population. It is indeed a challenge in respect of diagnosis, clinical aspects and therapy. SA is not only responsible for mental handicaps during daytime caused by disturbed sleep (increased tendency to doze or fall asleep, proneness to accidents), it will also enhance morbidity and mortality in aspect of cardiopulmonary and cardiovascular diseases (hypertension, cardiac insufficiency, disturbances of cardiac rhythm). All kinds of secondary and/or subsequent damage are reversible, provided diagnosis and rigidly introduced and maintained treatment have been performed well in time. SA can be diagnosed, treated and followed up by means of methods that can be flexibly employed outside the hospital, i.e. on an outpatient basis, such as questionnaires, MESAM IV, behavioural counselling, drug therapy). Within the framework of the current three-year project a stepwise concept was developed for diagnosis and treatment that also includes outpatient examination procedures. This system integrates anamnesis, outpatient monitoring, sleep laboratory, therapy and therapy control into a comprehensive feedback system of patient care. The following standardised procedural steps are included in the outpatient part of this system: baseline examination, treatment that can be performed on an outpatient basis, short-term, medium-term and long-term therapy follow-up. If these steps do not yield satisfactory results or if there is a high acute risk, the patient is subjected to in-patient treatment. At present, 683 first examinations and 420 follow-ups have been recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497459 TI - [Significance of a screening questionnaire for diagnosis of sleep apnea]. AB - More and more patients present with nocturnal respiratory disorders, especially with sleep apnoea (SA). This makes it mandatory to develop methods for preselecting the patients. A symptom assessment questionnaire was developed according to the Marburg stepwise concept on sleep apnoea diagnostics. Every patient completes this questionnaire as a matter of routine before he is given an appointment for an examination. The procedure to be followed depends on the evaluation of this questionnaire. Questions asked: Weight, height, use of soporifics and sleeping pills, hypertension, snoring, involuntary falling asleep, respiratory standstills, tendency to fall asleep during car driving and accidents in which the tendency to fall asleep was also involved. Three categories result from the evaluation: presence of sleep apnoea improbable (negative), more accurate details of symptoms mandatory (checking required) sleep apnoea probable (positive), patient is given an appointment date. This method was tested on 124 patients (108 male, 16 female, average age 50 yrs., average body-mass index 29.1, average apnoea index (AI) 12.8) who completed the questionnaire and were examined as outpatients, independent of the evaluation of the questionnaire, using the MESAM-IV system (nocturnal long-term recording of respiratory noises, heart rate, oxygen saturation and posture sensor). Measurements according to MESAM-IV system yielded in 69 patients (55.6%) and AI < 6 (apnoea-negative). 12 patients (9.7%) had AI 6-10 (checking required), and 43 AI < 10 (positive). Basing on evaluation of the questionnaire, 42 of 43 apnoea-positive patients had been correctly classified (98%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497460 TI - [Comparative use of MESAM IV and polysomnography in sleep-related respiratory disorders]. AB - The high prevalence of sleep-related respiratory disturbances among the male population requires development of reliable outpatient measurement systems enabling the selection of patients to be admitted to the sleep laboratory. MESAM IV is such a system. It can record for up to 18 hours via four sensors a patient's snoring sounds, heart rate, oxygen saturation and posture. To test the reliability of the instrument we compared parallel night measurements by MESAM IV and polysomnography (PSG) via the respective Respiratory Disturbance Indices (RDI = number of apnoeas plus hypopnoeas per hour). The group of subjects studied numbered 68 patients of the sleep laboratory suspected of having sleep-related respiratory disturbances (age 18-78 years, average 50.8 yrs.; height 164-192 cm, av. 175.2 cm; weight 40-160 kg, av. 99.3 kg; body mass index 13.8-49.5, av. 32.3). Assessment of the MESAM measurements was effected on the one hand by means of a computer programme (version 1.2) that is part of the system, and on the other hand by 3 independent evaluators, two of whom were already experienced in MESAM evaluation. Each evaluator was unaware of all personal and clinical data of the patients and of the results obtained by the other evaluators. Visual assessment was performed according to fixed criteria with the inclusion of all four measurement signals of the system, whereas two mutually independent respiratory disturbance indices (RDI) were calculated by computer evaluation. The results of the various MESAM IV evaluations were compared with those of polysomnography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497461 TI - [Clinical experience with the Apnea Check System in screening for sleep apnea]. AB - We examined 17 patients (3 female, 14 male) of 40 to 60 years of age suspected of suffering from sleep apnoea (SA) according to anamnesis and pulse oximetry, using the apnoea check system (AC) and by polysomnography (PS). AC measures the flow at the mouth and nose by means of thermistors and records the apnoea number, maximal duration of apnoea, and mean duration of apnoea (A mean). The PS-measured values: apnoea index (AI), maximal duration of apnoea (A max) and mean duration of apnoea (A mean) were taken to be equal to 100% and the AC-measured values were referred to these. AI (AC) was 76-577% of AI (PS). In 3 patients, AI (AC) was smaller than AI (PS), whereas in 14 patients it was greater. A max (AC) was 83-390% of A max (PS). In 11 patients A max (AC) was greater than A max (PS) and in 6 patients it was smaller. A mean (AC) was 56-223% of A mean (PS). In 9 patients A mean (AC) was greater and in 8 patients smaller than A mean (PS). PS had in 15 patients an AI > 10, in 2 patients < 10. In all patients, AC had an AI > 10. AC enabled identification of all patients suffering from sleep apnoea, and hence it appears to be suitable for screening. Further measurements in patients with AI < 10 will be necessary to examine the specificity. PMID- 8497462 TI - [Ambulatory monitoring of patients with suspected sleep apnea syndrome using a thermistor sensor in comparison with nocturnal polysomnography]. AB - Simple ambulatory monitoring methods can be used in step-by-step diagnosis of sleep apnoea syndrome to differentiate between high-risk and low-risk patients, or to exclude the syndrome for achieving more efficient utilisation of sleep laboratory facilities. The question was whether a new method using a thermistor sensor measuring respiration-conditioned thermal convection at the mouth and nose can reliably record the frequency of apnoea (ambulatory thermistor method = ATM). The study was subdivided into two sections. In phase I the respiratory impulses measured via ATM were polygraphically recorded in 20 patients simultaneously with conventional cardiopulmonary data of nocturnal polygraphy (heart rate, oxygen saturation, thorax and abdominal excursions and oronasal respiratory flow). 40 patients participated in phase II. During a first night the patients slept under ATM in their patient rooms. In the 2nd night nocturnal polygraphy was conducted with the parameters mentioned above; the results of both nights were then compared. Taking 35 phases of apnoea in one night as threshold or baseline value, a sensitivity of 100% and a specificity of 84.6% were attained in phase I, the simultaneous comparison of ATM and nocturnal polygraphy, in the recording of an enhanced nocturnal apnoea frequency by ATM. In phase 2 (1st night ATM, 2nd night polygraphy) ATM also yielded a sensitivity of 100% and a specificity of 76%. When measuring with a borderline value of 70 nocturnal phases of apnoea, ATM yielded a specificity and sensitivity of 100%, in phase 2 a sensitivity of 80.7% and a specificity of 88.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497463 TI - [Efficiency of portable sleep apnea screening instruments]. AB - Diagnosis of a sleep apnoea syndrome in severely snoring patients with diurnal sleepiness is growing in importance in the consulting rooms of general practitioners, internists, ENT specialists and pneumologists. However, time and cost reasons limit the diagnostic procedures conducted by practitioners to outpatient screening. Two different systems are presently available in Germany. The MESAM system (Madaus, Freiburg) records by means of a microphone and various electrodes the oxygen saturation, heart rate, snoring and sleeping position of the patient. The Apnoe-Check System (Medanz, Starnberg) determines the nasal and oral respiratory flow by means of a mask fitted with thermistors. Evaluation is accomplished in the case of MESAM via a conventional personal computer whereas with the Apnoea Check System the apnoeas and their duration can be read off direct from a writer. The cost ratio of these systems is approximately 3:1 (MESAM:Apnoea Check). Wie compared both systems by parallel measurements on 19 female and male patients and controlled the results obtained by measurements with a CO2 infrared absorption spectrometer in our sleep lab. A total of 3201 nocturnal events were recorded via MESAM and 1488 via the Apnoe-Check System. The highest number of apneas was recorded by MESAM in a patient with severe sleep apnea syndrome, namely, 546 apnoeas in one night. The lowest number of apnea events was experienced by a healthy male with 33 apneas in a night. With the Apnoe Check the maximum of nocturnal events was 255, the minimum being 8 events in one patient. In 64.6% of all nocturnal events there was time congruence for both systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497464 TI - [Validation study of the 10-channel Sidas 2010 registration unit for diagnosis of sleep-related respiratory disorders]. AB - We developed in cooperation with F. D. Stott, Oxford, the Mobile 10-Channel Unit SIDAS 10, a recording instrument for diagnosing sleep-related breathing disorders, to cope with the large number of patients requiring to be diagnosed. Studies that have already been published prove the clinical worth of this instrument that has been conceived as a mobile unit for the diagnosis of sleep related breathing disorders outside a conventional sleep laboratory. To test the validity of this unit the present study was designed as a comparative study of conventional polygraphs versus SIDAS recordings. METHOD: 20 unselected patients (18 men, 2 women), average age 54.8 (34-65) years, body mass index (BMI) 29.8 (20.2-46.2) kg/m2, were examined parallel for one night in the sleep laboratory. We compared the breathing a) recorded with nasal airflow, oesophageal pressure, oxygen saturation and b) with induction plethysmography, ITP (a non-invasive recording of intrathoracic pressure variations), nasal airflow and pulse oxymetry via SIDAS 2010. The writeouts were evaluated visually according to internationally valid criteria. RESULTS: We found 10 patients with an apnoea index (AI) > 10/h (mean AI 53.2), 4 patients with AI between 5 and 10/h (mean AI 6.4) and 6 patients with an AI < 5/h (mean AI 3.4). 5835 apnoeas and hypopnoeas were evaluated. The statistical analyses yielded the following results: equal classification of central apnoeas in 87%, of obstructive apnoeas in 90% and of mixed apnoeas in 92% of the cases; on the whole, 10% more hypopnoeas were classified in the SIDAS recordings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497465 TI - [Sleep analysis computer in diagnosis of sleep-related respiratory disorders]. AB - Sleep related breathing disorders influence the structure of sleep by considerably modifying the ratios of the individual sleep stages. The sleep analyses carried out by polysomnography in the diagnosis of sleep related breathing disorders have so far been evaluated manually according to the criteria of Rechtschaffen and Kales, since automatic systems do not permit standardised evaluation as yet. Automatic sleep analyses via SAC, however, has been developed further in recent years and has widened its scope and efficiency. It is now possible to perform a comprehensive sleep analysis via SAC by means of modified criteria after Rechtschaffen and Kales. The SAC determines individual curves in the EEG and EOG and includes in addition to the EEG parameters an automatic apnoea detection as well as detailed breathing and oxygen saturation analyses. The Sleep Analysis Computer (SAC) records 15 parameters (2 EEG, 2 EOG, 2 EMG, ECG, NAF, thoracic and abdominal breathing curves, oxygen saturation, body posture, optionally blood pressure = RR, CPAP etc.). This means that all the parameters required for diagnosing sleep related breathing disorders as well as their differential diagnosis can be determined. Within the framework of a blood pressure study, 16 patients (average 45.5 SD 4.6 years) were subjected to SAC measurement in addition to conventional PSG. The computer recordings were evaluated according to apnoea index, the form of the apnoea and the oxygen saturation desaturations. The evaluation yielded the following pattern: 4 patients with AI < 10, 8 patients with AI between 10 and 20, 4 patients with AI > 20. Obstructive apnoeas were seen in 6 patients, mixed apnoeas in 8 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497466 TI - [A new multichannel system for detection of sleep apnea syndrome]. AB - A new multichannel system is presented which records and analyzes polysomnographic data. The reasonably priced hardware and software makes the diagnosis and therapy of sleep apnea syndrome possible even in smaller internal departments. By using this system, adjustments to the nCPAP therapy can be undertaken. A newly developed analog-digital converter and software functions record simultaneously up to 24 channels. It performs the functions of commercially available instruments for induction plethysmography. The system has a modular setup. It is also possible to record special parameters, such as transcranial Doppler signals. Without any difficulty, instruments already used in the sleep laboratory can be included into this multichannel system. For instance, the screening device for the sleep apnea syndrome MESAM IV can be easily integrated. With this combination, it is possible to adjust sleep apnea patients to the nCPAP therapy by using the MESAM IV device. The software also enables analysis of breathing parameters and algorithmic revision of channels. In this way, filters can be integrated and amplitude calculations can be conducted. PMID- 8497467 TI - [Effect of obstructive sleep apnea on preload of the right heart]. AB - Obstructive sleep apnea (OSA) is characterized by a total inspiratory occlusion of the extrathoracic airways with persisting respiratory effort. During obstructive breathing efforts the intrathoracic pressure (ITP) falls below-20 Torr. This should augment venous return by depleting the blood from the extrathoracic veins into the thoracic veins, thus pre- and afterload of the right heart rises. Until now preload of the right heart during OSA was not measured. This study shows the filling pressures (tmPRA) of the right heart during OSA. In five patients the in- and expiratory right atrial pressure and the intrathoracic pressure were measured, beat by beat, during the non REM hour in which the most apnea episodes occurred. The tmPRA values were calculated as follows: tmPRA = PRA ITP. The rising tmPRA with falling ITP shows that the venous return, during apnea episodes, rises mostly unhampered. Only in one patient did a cut-off of the increasing tmPRA occur. This patient showed a flow limitation of venous return. Two more patients developed different trends. One part of the measurements led to a linear increase of tmPRA, the other part shows a plateau up from a certain ITP. In two patients tmPRA increases linearly, in the extreme, with decreasing ITP. This indicates no flow limitation of venous return. The results of this investigation suggest that the protective mechanism of the limitation of venous return, occurring under artificial conditions, does not regularly appear in patients with OSA. This leads to repetitive volume overloads of the right heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497468 TI - [Long-term registration of arterial blood pressure in sleep with noninvasive methods]. AB - Sleep related breathing disorders and essential hypertension are highly interrelated. Many different studies proved a casual relationship between the two disorders (1,2). In a clinical sleep laboratory diagnostics of hypertension has to be non-invasive. There are two completely different methodologies to record blood pressure noninvasively. Continuous methods using fingerphotoplethysmography can record apnea related cyclical variations of blood pressure beat to beat. Unfortunately the absolute value of the pressure readings is sensitive to the position of the finger sensor. Noncontinuous methods using arm cuff inflation preserve appropriate blood pressure values but these are only spot measures during the night. To make use of these it is necessary to record other sleep and respiration related signals in parallel. Both methods were applied in our sleep laboratory and results are presented. PMID- 8497469 TI - [Prevalence of obstruction of extrathoracic and intrathoracic airways in patients with arterial hypertension]. AB - The object of this study was to find out the difference between patients with and without arterial hypertension in respect of oxygen desaturation, obesity and obstructive sleep apnoea. 497 men were examined who had chronic diseases of the respiratory passages and whose average age was mean = 45.9 +/- 11.2 years, the Broca index being 109 +/- 17%. 106 men (age mean = 48.6 yrs, Broca index = 118.4, systolic blood pressure according to Riva-Rocci mean = 154.6 mmHg, diastolic 101.4 mmHg) had arterial hypertension. 391 men (age mean = 45.1 yrs, Broca = 107.1, BP/RRsys mean = 130.5 mmHg, BP/RRdia mean = 82.5 mmHg) had normal blood pressure. Another subdivision was effected according to frequency of oxygen desaturations measured according to frequency of oxygen desaturations measured during 8 hrs sleep (SaO2 > 90%, frequency > 80/8 hrs) and the Broca index (> 120%). 31.1% of the hypertensive and 16.6% of the normotensive patients had more than 80 SaO2 drops/8 hrs to below 90%. 44.7% of obese hypertensives and 37.1% of obese normotensives were suspected of suffering from obstructive sleep apnoea. 45 highly suspicious patients were examined by polysomnography. This was the case with 19.8% of the hypertensives and 6.1% of the normotensives. 78.9% of the hypertensives examined via polysomnography because of suspicion of pulse oximetry and/or obesity had in fact an apnoea index > 10, whereas only 41.2% of the normotensives selected according to the same criteria demonstrated this phenomenon. On the whole, patients suffering from arterial hypertension were at markedly higher risk of obstructive sleep apnoea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497470 TI - [Quantitative studies assessing daytime fatigue, vigilance and attention before and after nCPAP therapy of sleep apnea syndrome]. AB - As far as day symptoms are concerned, excessive drowsiness and tendency to fall asleep are signposts in diagnosis and treatment of sleep apnoea syndrome exercising a decisive influence on the patient's quality of life. Recent studies (Findley et al., 1988; George et al., 1987; Aldrich et al. 12/89) have shown that the patients are additionally endangered by an increased accident risk. After controversial data in the literature in respect of the usefulness of neuropsychological testing when going into this problem we tried to develop an alternative to MSLT (Multiple Sleep Latency Test) which is the clinical standard, since the technique required is so complicated that it is only rarely used in everyday practice. We aimed at easy application in clinical daily routine. We examined via computer-assisted neuropsychological testing the attention and concentration performance in 14 patients having a sleep apnoea syndrome of moderate severity, before and after a short treatment course of three nights with nCPAP, and compared the results with those obtained in 17 patients with a similar pattern of complaints in whom a sleep apnoea syndrome could be excluded. The test lasted for 45 minutes in each case. Various reaction time tests were performed with acoustical, optical and combined phenomena. The reaction times as well as the number of errors were noted. We could show that the treatment course resulted in an improvement of certain attention and concentration performances, above all however in continuous attention against a monotonous stimulation background (vigilance)--and improvement that can be measured already after a short therapy period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497471 TI - [Nocturnal hypoxia--its relevance with reference to sleep structure in patients with coronary heart disease]. AB - A disorder in the physiological structure of the sleep cycles (macrostructure) is known to occur both in patients with sleep apnoea (SA) and coronary heart disease (CHD). The study presented here was concerned with the problem whether the sleep structure in patients suffering from CHD and apnoea-conditioned hypoxia is greatly disturbed e.g. by myocardial ischaemia. Polysomnographic recordings including EEG, EOG, EMG and 6-channel ECG were performed for 6 nights in 30 patients suffering from sleep apnoea (AI > 10/h) and/without CHD. The average age of the patients was 57.9 years (range 47-68 yrs). The 2nd, 4th and 6th nights were subjected to fine analysis. In 6 patients it was possible to detect a total of 144 episodes with nocturnal myocardial ischaemia, 123 of these during cumulative apnoea and oxygen desaturation. The 30 patients spent on the average 67.1% in sleep stages I and II, 14.9% in deep sleep (stages III and IV) and 18% in REM sleep. 77.8% of the ischemie, episodes occurred during REM sleep and only 1.4% during the deep sleep stages. Sleep during myocardial ischaemia showed significantly more arousals than to control periods without ischaemia. There was furthermore a dependence of the degree of arousal on the degree of oxygen desakivations during apnoea. I. Patients suffering from CHD and sleep apnoea are endangered by nocturnal hypoxia-conditioned myocardial ischaemia which in turn can lead to increased electrical instability. II. The macrostructure of the sleep of patients suffering from CHD and sleep apnoea is comparatively as disturbed as that of patients with apnoea without CHD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497472 TI - [Therapy control of theophylline evening dosage in patients with sleep-related respiratory disorders--follow-up study]. AB - We conducted a prospective study to perform classification according to responder types and follow-up during theophyllin treatment (500 mg/d) in a group of (up to now) 65 patients suffering from sleep apnoea. Changes in the apnoea index (AI) and clinical symptoms were taken as response criteria. A significant AI reduction was seen during a follow-up period of 3 months. At the last control measurement after 6 months no significant change has been detected so far. 10 patients were classified as Type I responders (improvement in initial AI 60%, over the total period at least 25%). No patient had a responder type II profile. 13 patients were nonresponders (improvement in initial AI and over the whole period not more than 25%, no improvement in the pattern of clinical symptoms). 13 patients dropped out of the trial due to non-compliance. Side effects typical of theophyllin leading to discontinuation of the treatment course occurred in 5 patients. 22 patients have not yet completed the course at the time of writing. Standardised questioning of patients showed a definite improvement in feeling tone, especially with regard to the tendency to fall asleep during the day and refreshed feeling in the morning. Nocturnal complaints occurred in only a few isolated cases. Hence, administration of theophyllin retard preparations in evening doses of 500 mg/d remains a meaningful therapeutic approach to sleep apnoea. PMID- 8497473 TI - [Diagnostic findings in patients with obstructive sleep apnea syndrome in nCPAP therapy]. AB - The outpatient measurement with the ME-SAM IC system, including the analysis of heart rate, respiration sounds, continuous oxygen saturation and body position, is an important part in a stepped concept for diagnosis and therapy of patients with an obstructive sleep apnea syndrome (OSAS). We investigated the importance of these parameters as well as age and Broca in relation to the continuous positive airway pressure determined in the sleep laboratory. In this study we present the first 60 patients (56 m, 4 f) treated successfully with nCPAP. The mean age was 53.1 +/- 8.6 years, the Broca Index 133.6 +/- 22.9, the respiratory disturbance index (RDI, apnea + hypopnea index) 48.1 +/- 22.7, the mean nocturnal oxygen saturation 90.4 +/- 3.8% and the mean minimal oxygen saturation 84.4 +/- 4.2%. We found positive significant correlation between Broca, RDI and oxygen saturation as well as between Broca and age. The mean effective continuous positive airway pressure was 9.7 +/- 2.1 cm H2O in our group of OSAS patients. With an increase in RDI and with a decrease in age and oxygen saturation we found an significant increase in the effective continuous positive airway pressure. A positive correlation between Broca and air pressure could be seen, but was not significant. Our data show that there is a strong correlation between constitution, the outpatient measurement with MESAM-system and the effective positive airway pressure in patients with a pronounced obstructive sleep apnea syndrome (RDI > 15 and marked clinical symptoms). The knowledge about these relationships should be considered in the nCPAP therapy and during the long term medical care of treated patients. PMID- 8497474 TI - [Measuring circadian core temperature periodicity without masking in obstructive sleep apnea]. AB - Although close interactions between sleep respectively sleep disturbances and the circadian system are known, chronobiological aspects have not been taken into account sufficiently in investigation and therapy of obstructive sleep apnea (OSA). We carried out a 24-hours lasting constant routine. Considering the circadian course of core temperature, patients with OSA show an impairment of the circadian system, which improves after three nights with nCPAP-treatment. PMID- 8497475 TI - [Continuous noninvasive blood pressure measurement in obstructive sleep apnea syndrome without and with CPAP therapy]. AB - The obstructive sleep apnea syndrome is accompanied with episodic increases of systemic blood pressure (B.P.) and possibly with persistent hypertension. to find out the influence of nCPAP therapy on systemic blood pressure in sleep apnea patients, 10 patients (apnea index 9-51/h) were monitored by means of continuous noninvasive blood pressure measurement during polygraphy, circulation was examined before and 2-7 days after CPAP therapy. Every 30 minutes a 2-minute period of the systolic and diastolic B.P. was visually averaged and from these data the mean pressure of 7 hours nocturnal sleep was calculated. The mean systolic pressure before therapy was 139 +/- 32 mmHg and decreased to 122 +/- 14 mmHg under nCPAP (significant), the mean diastolic pressure before therapy was 74 +/- 17 mmHg and decreased to 64 +/- 8 mmHg under nCPAP. The maximal B.P. during the 7-hour measurement decreased from 155 +/- 27 mmHg to 137 +/- 20 mmHg under nCPAP. PMID- 8497476 TI - [Hemodynamics and sleep structure in attempted weaning after nCPAP ventilation therapy of obstructive sleep apnea syndrome]. AB - nCPAP (continuous positive airway pressure) treatment is presently the standard therapy in marked obstructive sleep apnoea syndrome. Fundamentally, this is a long-term treatment. Various authors have been making different recommendations in respect of the frequency of application, based partly only on the patient's individual pattern of complaints and symptoms. Our study aimed at examining the short-term nocturnal effects of discontinuing the treatment course in 12 patients, using polysomnography as a diagnostic tool. Results showed that directly after discontinuation of therapy the sleep structure, respiration during sleep and the nocturnal blood pressure pattern returned to baseline findings. It is concluded from this that nCPAP treatment should be strictly adhered to every night to minimise the risk of cardiovascular complications in the patients concerned. PMID- 8497477 TI - [Indications and application of BiPaP therapy]. AB - BiPAP allows the independent adjustment of in- and expiratory pressure. BiPAP may thus be used as a "physiologic" CPAP if high expiratory pressure values are not tolerated or as a pressure limited ventilator in pts. suffering from central sleep related breathing disorders (SRBD). 12 pts with SRBD were treated with nBiPAP: 7 did not tolerate the expiration against the elevated pressure, 4 pts suffering from MSA who still presented relevant CSA or central Hypoventilation during nCPAP and 1 pt. with CSA who did not respond to nCPAP. Mean age was 52.3 y (range 33-70) and mean broca index was 149.6 (range 115-254). RDI before therapy ranged between 33-152/h (mean value 79/h); in the five pts. who tolerated nCPAP, the reduction of the RDI obtained was considered insufficient (RDI during nCPAP: 16-71/h). During BiPAP mean RDI was 6.8/h (range 1-17) at pressure levels of 10/7 to 16/13 cm H2O (inspiratory/expiratory pressure) in those pts. that had not tolerated CPAP and 7.9/h (range 2-16.5) in the pts. suffering from central SRBD: in one pt. BiPAP could successfully replace a combined treatment with CPAP and IPPV. 11 pts. are using BiPAP for 10 to 25 months (mean value 13.5) now at home. If CPAP proves ineffective (central SRBD, high expiratory pressure) BiPAP constitutes an effective alternative therapy. PMID- 8497478 TI - [Hypertension at awakening in sleep apnea]. AB - There is an increased mortality among patients with sleep related breathing disorders. This fact is largely ascribed to arterial hypertension and its associated cardiovascular risk with which sleep apnoea is interlinked, as is known from epidemiological and clinical studies. The present study was based on 20 males suffering from arterial hypertension and sleep apnoea, measuring the blood pressure changes 4 hours before and 4 hours after waking up, in each case without therapy and after 8 weeks' treatment with a combination preparation made up from verapamil and a potassium-saving diuretic. Besides the usual polysomnographic measurements in the sleep laboratory blood pressure was measured intra-arterially and continually, each time on two consecutive days. The average age was 53 (39-70) years, and the average of Broca's index was 129 (109-158). It was found that blood pressure values rise already 2-3 hours before waking up and maximum is attained subsequent to waking. Under therapy the minimal systolic values before waking dropped from 132.8 mmHg (+/- 22.8) to 119.4 mmHg (+/- 11.9) (p < 0.01) and the maximal values after awakening were reduced with 149.8 mmHg (+/- 27.7) vs 132.7 mmHg (+/- 25.4) (p < 0.01) without dropping to hypotensive levels. Under therapy there was a less marked and also slower rise in blood pressure with time. Besides pointing to the fact that endogenous mechanisms also influence blood pressure patterns in addition to the well-known exogenous influences, the study proved the favourable therapeutic action of treatment with an antihypertensive drug that is effective for a period of 24 hours. PMID- 8497479 TI - [Surgical treatment of obstructive sleep apnea by modifying the facial skeleton with reference to cephalometric parameters]. AB - Cephalometry: Morphologic alterations can be found in a great deal of patients with OSAS, predisposing to the rise of sleep apnea. In addition to preexisting investigations we developed a cephalometric analysis to judge these alterations in patients with OSAS. Comparing 160 patients to healthy people pharyngeal obstructions could be found in more than one third of the patients, usually combined with a retrognathic dolichofacial morphology. SURGICAL PROCEDURE: As successful treatment of our own patients shows, curing of obstructive sleep apnea is possible in respect of these cephalometric alterations. The basis of surgical treatment consists of surgical advancement of the mandible by sagittal split osteotomy and advancement of the maxilla by Le Fort I-osteotomy. Advancement surgery must be done in consideration of the morphologic alterations mentioned above. Additionally secondary procedures can be taken into account as genioplasty, soft-tissue-corrections or corrections of the upper airways. PMID- 8497480 TI - Length distribution of CDRH3 in antibodies. AB - Sequences of the third complementarity determining region of antibody heavy chains (CDRH3s) are listed according to their length. Human sequences vary from 2 to 26 amino acids residues, but less extensively in other species. When combined with the other five complementarity determining regions, this enormous length variation of CDRH3, together with amino acid substitutions in their sequences, can provide a very large number of antibody specificities and can influence the shape of antibody combining sites. PMID- 8497481 TI - Refined structure of bovine carbonic anhydrase III at 2.0 A resolution. AB - The three-dimensional structure of bovine carbonic anhydrase III (BCA III) from red skeletal muscle cells has been determined by molecular replacement methods. The structure has been refined at 2.0 A resolution by both constrained and restrained structure-factor least squares refinement. The current crystallographic R-value is 19.2% and 121 solvent molecules have so far been found associated with the protein. The structure is highly similar to the refined structure of human carbonic anhydrase II. Some differences in amino acid sequence and structure between the two isoenzymes are discussed. In BCA III, Lys 64 and Arg 91 (His 64 and Ile 91 in HCA II) are both pointing out from the active site cavity forming salt bridges with Glu 4 and Asp 72 (His 4 and Asp 72 in HCA II), respectively. However, Arg 67 and Phe 198 (Asn 67 and Leu 198 in HCA II) are oriented towards the zinc ion and significantly reduce the volume of the active site cavity. Phe 198 particularly reduces the size of the substrate binding region at the "deep water" position at the bottom of the cavity and we suggest that this is one of the major reasons for the differences in catalytic properties of isoenzyme III as compared to isozyme II. PMID- 8497482 TI - Crystallization and preliminary X-ray diffraction data of two heparin-binding fragments of human fibronectin. AB - Two different heparin-binding fragments of human fibronectin have been crystallized in forms which are suitable for crystal structure analyses. The 30 kDa hep-2A fragment, consisting of type III domains 12-14, was crystallized from solutions containing ammonium sulfate or polyethylene glycol 6000. The crystals grown in ammonium sulfate solutions were orthorhombic with space group I222 or I2(1)2(1)2(1) with a = 68.1 A, b = 88.6 A, and c = 144.9 A. The crystals grown in polyethylene glycol solutions are hexagonal with space group P6(1)22 or P6(5)22 with a = b = 66.7 A and c = 245.7 A. The 40 kDa hep-2B fragment, consisting of type III domains 12-15, was also crystallized from solutions containing ammonium sulfate with the addition of glycerol. Glycerol proved an effective agent for reducing the number of crystals in the crystallization experiments, and thus, increasing the size of the crystals in these experiments. This crystal form is nearly isomorphous to the orthorhombic form of the hep-2A fragment with space group I222 or I2(1)2(1)2(1) and a = 67.5 A, b = 87.0 A, and c = 144.3 A. All crystal forms diffract to at least 3.5 A resolution and contain a single molecule in the asymmetric unit. PMID- 8497483 TI - A novel computer modeling approach to the structures of small bioactive peptides: the structure of gonadotropin releasing hormone. AB - A novel computer modeling approach suitable for the structure analysis of small bioactive peptides has been developed. This approach involves identification of conformational patterns in protein structure data bank based on the sequence homology with the bioactive peptide. The models built on the basis of this homology and having common conformational patterns are analyzed under the structural constraints derived from the activity data of various synthetic analogs of the peptide. Application of this procedure to the gonadotropin releasing hormone (GnRH) resulted in a library of possible structures for GnRH, 9 among which shared a common beta-turn. Further analysis of the structures containing the beta-turn motif, in the context of the structure-activity data, led to a model for the active conformation of GnRH. The topology of the putative receptor binding site of the hormone is defined by a contiguous surface formed through an appropriate juxtaposition of the N-terminal pGlu1, the guanidyl group of Arg8, aromatic side chain of Trp3, and the Gly10-NH2 at the C-terminal end. PMID- 8497484 TI - Recombinant antineuraminidase single chain antibody: expression, characterization, and crystallization in complex with antigen. AB - The variable heavy (VH) and variable light (VL) genes of NC10, a monoclonal antibody with specificity toward N9 neuraminidase (NA), were cloned and sequenced. A single chain Fv (scFv) fragment of NC10, consisting of VH and VL domains joined by a peptide linker, was designed, constructed and expressed in the E. coli expression vector pPOW. The N-terminal secretion signal PelB directed the synthesized protein into the periplasm where it was associated with the insoluble membrane fraction. An octapeptide (FLAG) tail was fused to the C terminus of the single chain Fv to aid in its detection and remained intact throughout the protein purification process. NC10 scFv was purified by solubilization of the E. coli membrane fraction with guanidinium hydrochloride followed by column chromatography. The purified NC10 scFv showed binding affinity for its antigen, NA, 2-fold lower than that of the parent Fab. The complex between NA and the scFv has been crystallized by the vapor diffusion method. The crystals are tetragonal, space group P42(1)2, with unit cell dimensions a = b = 141 A, c = 218 A. PMID- 8497485 TI - Catalysis by dienelactone hydrolase: a variation on the protease mechanism. AB - Dienelactone hydrolase (DLH), an enzyme from the beta-ketoadipate pathway, catalyzes the hydrolysis of dienelactone to maleylacetate. Our inhibitor binding studies suggest that its substrate, dienelactone, is held in the active site by hydrophobic interactions around the lactone ring and by the ion pairs between its carboxylate and Arg-81 and Arg-206. Like the cysteine/serine proteases, DLH has a catalytic triad (Cys-123, His-202, Asp-171) and its mechanism probably involves the formation of covalently bound acyl intermediate via a tetrahedral intermediate. Unlike the proteases, DLH seems to protonate the incipient leaving group only after the collapse of the first tetrahedral intermediate, rendering DLH incapable of hydrolyzing amide analogues of its ester substrate. In addition, the triad His probably does not protonate the leaving group (enolate) or deprotonate the water for deacylation; rather, the enolate anion abstracts a proton from water and, in doing so, supplies the hydroxyl for deacylation. PMID- 8497486 TI - Prediction of protein folding class from amino acid composition. AB - An empirical relation between the amino acid composition and three-dimensional folding pattern of several classes of proteins has been determined. Computer simulated neural networks have been used to assign proteins to one of the following classes based on their amino acid composition and size: (1) 4 alpha helical bundles, (2) parallel (alpha/beta)8 barrels, (3) nucleotide binding fold, (4) immunoglobulin fold, or (5) none of these. Networks trained on the known crystal structures as well as sequences of closely related proteins are shown to correctly predict folding classes of proteins not represented in the training set with an average accuracy of 87%. Other folding motifs can easily be added to the prediction scheme once larger databases become available. Analysis of the neural network weights reveals that amino acids favoring prediction of a folding class are usually over represented in that class and amino acids with unfavorable weights are underrepresented in composition. The neural networks utilize combinations of these multiple small variations in amino acid composition in order to make a prediction. The favorably weighted amino acids in a given class also form the most intramolecular interactions with other residues in proteins of that class. A detailed examination of the contacts of these amino acids reveals some general patterns that may help stabilize each folding class. PMID- 8497487 TI - Computer modeling and folding of four-helix bundles. AB - In the context of simplified models of globular proteins, the requirements for the unique folding to a four-helix bundle have been addressed through a new Monte Carlo procedure. In particular, the relative importance of secondary versus tertiary interactions in determining the nature of the folded structure is examined. Various cases spanning the extremes where tertiary interactions completely dominant to that where tertiary interactions are negligible have been explored. Not surprisingly, the folding to unique four-helix bundles is found to depend on an adequate balance of the secondary and tertiary interactions. Moreover, because the simplified model is composed of spheres representing alpha carbons and side chains, the geometry of the latter being based on small real amino acids, the role played by the side chains, and the problems associated with packing and hard-core repulsions, are considered. Also, possible folding intermediates and their relationship with the experimentally observed molten globule state are explored. From these studies, a general set of rules is extracted which should aid in the further design of more detailed protein models adequate to more fully investigate the protein folding problem. Finally, the relationship between our conclusions and experimental work with specifically designed sequences is briefly discussed. PMID- 8497488 TI - An empirical energy function for threading protein sequence through the folding motif. AB - In this paper we present a new residue contact potential derived by statistical analysis of protein crystal structures. This gives mean hydrophobic and pairwise contact energies as a function of residue type and distance interval. To test the accuracy of this potential we generate model structures by "threading" different sequences through backbone folding motifs found in the structural data base. We find that conformational energies calculated by summing contact potentials show perfect specificity in matching the correct sequences with each globular folding motif in a 161-protein data set. They also identify correct models with the core folding motifs of hemerythrin and immunoglobulin McPC603 V1-domain, among millions of alternatives possible when we align subsequences with alpha-helices and beta-strands, and allow for variation in the lengths of intervening loops. We suggest that contact potentials reflect important constraints on nonbonded interaction in native proteins, and that "threading" may be useful for structure prediction by recognition of folding motif. PMID- 8497489 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Service. PMID- 8497490 TI - Calcium homeostasis and eicosanoid formation in human platelets. PMID- 8497491 TI - Ingestion of marine oil reduces excretion of 11-dehydrothromboxane B2, an index of intravascular production of thromboxane A2. AB - We evaluated the effect of anchovy oil supplementation on the endogenous production of thromboxane A2 by measuring the excretion of its stable metabolite, 11-dehydrothromboxane B2 (11-DTXB2), in 24-h urine. In a longitudinal study, 35 male volunteers consumed a controlled basal diet for two experimental periods lasting a total of 20 weeks. During period 1 (10 weeks) the diet was supplemented with placebo (PO) capsules (15 x 1 g/d) consisting of a blend of fats approaching the fatty acid profile of the basal diet. During period 2 the subjects received 15 x 1 g/d capsules of fish oil concentrate (FOC). PO and FOC capsules contained 1 mg alpha-tocopherol per gram of fat as antioxidant. A 38% reduction of 11-DTXB2 excretion was observed after 10 weeks of FOC supplementation (period 2, n-6/n-3 PUFA ratio = 2.3), compared to an identical period of PO supplementation (period 1, n-6/n-3 = 12.5), p = 0.0001. The 11-DTXB2 excretion reduction (delta) fits the quadratic equation delta = 136.0038-0.3178(tx1)-0.0002(tx1)2, (R2 = 0.8944), where tx1 is the excretion rate at the end of period 1. This finding supports the hypothesis that the antithrombotic effect of marine oil is mediated, at least in part, by diet-induced shifts in the eicosanoid system. PMID- 8497492 TI - Changes in phospholipase A2 activity of the rabbit ampullary epithelium by ovarian steroids. AB - Phospholipase A2 (EC 3.1.1.4) activity of the ampullary epithelium from rabbit oviducts was compared in the presence of various ovarian steroids to assess how they could modulate prostaglandins (PG) biosynthesis in the oviduct. The phospholipase A2 (PLA2) activity of the cells from ovariectomized rabbits (control) was 190.8 +/- 9.8 pmol/min/mg. The PLA2 activity of the cells from progesterone-treated rabbits was 156.0 +/- 41.8 pmol/min/mg and was not significantly different from the control activity. However, the PLA2 activity of the cells from the estrogen-treated rabbits was 233.5 +/- 29.0 pmol/min/mg, which was significantly higher than the control activity (p < 0.05). On the other hand, the PLA2 activity of the cells from progesterone-treated rabbits after being primed with estrogen was 116.3 +/- 25.9 pmol/min/mg, which was significantly lower than the control activity (p < 0.01). These results suggest that the effects on PLA2 activity of ovarian steroids could regulate the local production of PG which plays a role in both smooth muscle contractility and ciliary activity. PMID- 8497493 TI - Induction of apoptosis in blood cells from a patient with acute myelogenous leukemia by SC41661A, a selective inhibitor of 5-lipoxygenase. AB - Participation of leukotriene products in normal ex vivo hematopoiesis is well established. With increasingly specific inhibitors of lipoxygenases, it becomes possible to more closely define any participation of their biosynthetic products in these events. We cultured chronic myelogenous leukemia cells from the peripheral blood of several patients in blast crisis with three inhibitors of lipoxygenases: ETYA, and the more selective A63162 (Abbott) or SC41661A (Searle). All three agents reduced labelling of DNA with H3 thymidine measured at 4 h and reduced cell numbers by 72 h. An antisense deoxyoligonucleotide to the 5 lipoxygenase mRNA 'start' codon inhibited DNA synthesis at 24 h, as did two control oligonucleotides. Marked nuclear ultrastructural changes characteristic of apoptosis were induced by SC41661A in a subset of cells with the ultrastructure of promyelocytes. Whether this response characterizes a common pattern of this subset of leukemic cells to SC41661A, if damage to mitochondria with reduced function of bcl-2 protooncogene product located at that site might have contributed or some other mechanism was responsible, and if inhibition of 5 lipoxygenase activity was involved, are questions to be decided in the future. PMID- 8497494 TI - Is there cross-refractoriness between phospholipase A2 and the calcium ionophore A23187 in the stimulation of uterine prostaglandin production? AB - Phospholipase (PL) A2 increased the outputs of prostaglandin (PG) F2 alpha, PGE2 and 6-keto-PGF1 alpha from the mid-cycle guinea-pig uterus, but repeating the PLA2 treatment 1 h later failed to increase uterine PG output. Similarly, A23187 increased PG output from the mid-cycle guinea-pig uterus, but repeating the A23187 treatment 1 h later produced a very much smaller stimulatory effect. Thus the guinea-pig uterus showed complete refractoriness to PLA2 and partial refractoriness to A23187, as regards the stimulation of uterine PG production, when the uterus is treated with the same compound after an interval of 1 h. However, when the mid-cycle guinea-pig uterus was treated with PLA2 1 h after being treated with A23187, or was treated with A23187 1 h after being treated with PLA2, the second compound produced a normal stimulation of PG output and was not affected, therefore, by treatment with the first compound. Consequently, there is no cross-refractoriness between PLA2 and A23187 as regards their stimulatory effects on PG production by the guinea-pig uterus. PMID- 8497495 TI - Complement 5a induces in vivo synthesis of cysteinyl leukotrienes in rats. AB - The complement derived anaphylatoxin complement 5a (C5a) is suggested to be involved in the pathogenesis of various types of diseases including endotoxic or anaphylactic shock. Studies in our laboratory demonstrated a marked and sustained reduction in renal blood flow and glomerular filtration rate after infusion of a low dose of recombinant C5a (rC5a). Renal rC5a effects were inhibited by leukotriene (LT) and thromboxane antagonists suggesting that the effects were mediated by LT. To elucidate the mechanisms of C5a effects, we monitored the biliary excretion rate of the stable metabolite, N-acetyl-LTE4, by reversed phase high performance liquid chromatography (HPLC). Rats in the experimental group were administered rC5a intravenously at 0.5 micrograms/min for 10 min. Biliary N acetyl-LTE4 excretion was significantly increased following rC5a infusion, 0.03 ng/microliters bile to 0.129 ng/microliters. The bile flow in the experimental group was reduced about 39% by rC5a, while bile flow of the control group increased by 20% during the observation period. Infusion of rC5a resulted in an increase of arterial hematocrit from 44.7% to 48.7%, whereas blood pressure was not significantly altered in experimental and control groups. Our results suggest the in vivo effects of C5a to be mediated by cysteinyl leukotrienes, which may be important in the pathogenesis of septic, anaphylactic or traumatic shock. PMID- 8497496 TI - Informed consent to defensive medicine: letting the patient decide. PMID- 8497497 TI - The early birth control movement: role of the nineteenth-century American physician. PMID- 8497498 TI - The rise and fall of socialized medicine in Britain: 1948-1991. PMID- 8497499 TI - The narrowing of medicine. PMID- 8497500 TI - Frederick A. Cook, M.D.--physician and polar explorer. PMID- 8497501 TI - The quality of drinking water: some lessons from history. PMID- 8497503 TI - Geraldine's kidney machine. PMID- 8497502 TI - Can the doctor's burden be shifted to the patient? PMID- 8497504 TI - Operating on family members. PMID- 8497505 TI - Remembrances and euphemisms. PMID- 8497506 TI - The mind-body problem. PMID- 8497507 TI - A question of plagiarism. PMID- 8497508 TI - Pathology in historical perspective. PMID- 8497509 TI - A study of the clinical test of sensory interaction and balance. AB - BACKGROUND AND PURPOSE: The ability to maintain an upright position during quiet standing is a useful motor skill. The Clinical Test of Sensory Interaction and Balance is an inexpensive, easily administered test that provides information about the ability to stand upright under several sensory conditions. SUBJECTS: Three groups of neurologically asymptomatic (AS) adults, divided by age into younger, middle-aged, and older groups, participated in the study. A fourth group comprised subjects diagnosed with vestibular disorders. METHODS: Timed performances under six different conditions were compared across groups. RESULTS: Subjects with vestibular disorders were significantly impaired on performance when compared with age-matched AS subjects. Older AS and vestibularly impaired subjects had greater variation in their scores than did younger AS subjects. CONCLUSION AND DISCUSSION: This test is a useful screening tool for examining static standing balance. PMID- 8497510 TI - Treatment of a large infected thoracic spine wound using high voltage pulsed monophasic current. AB - This case report describes the use of electrical stimulation with high voltage pulsed monophasic current for treatment of a large, infected wound of the thoracic spine, following a surgical debridement procedure. The patient was a 21 year-old man with spastic quadriplegic cerebral palsy who was dependent for all self-care and was severely mentally retarded. The initial wound size was as follows: length = 17 cm, top width = 7.5 cm, middle width = 5.5 cm, bottom width = 2 cm, and depth = 5 cm. The wound was infected with Staphylococcus aureus. The initial treatment consisted of 60 minutes of electrical stimulation (20 minutes of negative polarity followed by 40 minutes of positive polarity) once daily. The frequency of treatment was increased to twice daily after 2 weeks. Total treatment duration was 10 weeks. The patient received antibiotic treatment and daily nursing wound care in addition to electrical stimulation treatment. The wound was completely closed after 10 weeks of treatment. The possible role of high voltage pulsed monophasic current in accelerating the wound-healing process is discussed. PMID- 8497511 TI - Effects of age and resistance training on skeletal muscle: a review. AB - As humans age, there is a decrease in the ability of skeletal muscle to generate force. This review describes alterations in the neuromuscular systems of humans and animals that may be responsible for the diminished force-generating capacity of older muscles. The effects of resistance training on the force-generating capacity of older muscles in humans and on the neuromuscular systems of humans and animals are then examined. The age-related decline in force-generating capacity may be due, in part, to a loss of motor units and to a decline in muscle mass. Fiber atrophy and, possibly, loss of muscle fibers contribute to the decline in muscle mass in older persons. High-intensity resistance training appears to attenuate the age-related decline in force-generating capacity in humans and cause fiber hypertrophy of old muscle fibers. Investigations of the effects of age on the neuromuscular system and of the effects of resistance training on the neuromuscular system and the functional capacity of older persons are essential for the development of cost-effective interventions that will increase the physical capacity of older persons. PMID- 8497512 TI - Reaction and movement times in patients with hemiparesis for unilateral and bilateral elbow flexion. AB - BACKGROUND AND PURPOSE: This work was designed to study the effects of bilateral elbow flexion on the reaction and movement times of the impaired upper extremity of patients with hemiparesis. SUBJECTS: The subjects consisted of an experimental group of patients with hemiparesis (n = 25) and a control group of age-matched healthy volunteers (n = 26). METHODS: Each subject performed three sets of 16 elbow flexion trials. Two of these sets required unilateral movements, one for each upper extremity. The third set of movements required simultaneous elbow flexions of both upper extremities. In each trial, subjects were instructed to flex their elbows in response to an auditory signal from a supported initial position of 150 degrees through a goal orientation of 120 degrees. "Reaction time" was defined as the time between the auditory signal and movement initiation. "Movement time" was defined as the time between movement initiation and the completion of 30 degrees of elbow flexion. RESULTS: When subjects were asked to bilaterally flex their elbows, the reaction and movement times increased in both extremities. CONCLUSION AND DISCUSSION: It was speculated that in patients with hemiparesis, movement time of the nonparetic extremity in the bilateral task is limited by the rate of performance of the paretic extremity. The decrease in speed of these performance-determining variables in the bilateral task warrants consideration during physical therapy intervention for patients with hemiparesis. PMID- 8497513 TI - The application of generalizability theory to reliability assessment: an illustration using isometric force measurements. AB - BACKGROUND AND PURPOSE: The objective of this study was to examine the potential use of the generalizability theory for assessing reliability of muscle force measurements in clinical applications. Reliability is expressed in terms of standard error of measurement (SEM) and the indexes derived from the SEM. Using generalizability theory, potential sources of measurement error can be recognized and estimated. SUBJECTS: Ten healthy women, aged 23 to 47 years (means = 29.5, SD = 7.1), participated in the study. METHODS: The method is illustrated by presenting a pilot study. Repeated measurements of maximal isometric knee extension force were carried out by two therapists. The time interval between measurement occasions was 1 week. A functional prototype of a hand-held dynamometer was used, and measurements were carried out according to standardized test protocols. RESULTS: Relatively important sources of measurement error were associated with interaction effects between subject and therapist as well as with interactions including the factor occasion. The SEM of the net knee moment was estimated for various hypothetical applications of the dynamometer. CONCLUSION AND DISCUSSION: It is concluded that the SEM, the corresponding confidence interval, and the smallest detectable difference are practical measures for expressing reliability of measurements on an individual. Generalizability theory is a powerful tool for estimating the magnitude of multiple sources of measurement error and for assessing the reliability of measurements tailored to specific clinical applications. PMID- 8497515 TI - New partnerships. PMID- 8497514 TI - Treating the person as a whole. PMID- 8497516 TI - New partnerships. PMID- 8497517 TI - Cancer and ultrasound: a warning. PMID- 8497518 TI - Cervical spine subluxation associated with congenital muscular torticollis and craniofacial asymmetry. AB - The relationship between craniofacial asymmetry, congenital muscular torticollis, and cervical spine subluxation was examined in a study of 30 children who presented to our Craniofacial Program from 1987 through 1990. Twenty-six of the 30 patients had craniofacial asymmetry and muscular torticollis without true suture synostosis documented by head and neck CT scans. These 26 patients had positional skull molding with consistent flattening of the contralateral occipitoparietal region and the ipsilateral fronto-orbital region relative to the side of the torticollis. Thirteen of the 26 patients also were found to have a C1 C2 subluxation. C1 was rotated forward of C2 on the side contralateral to the muscular torticollis in 12 of 13 patients. None of the patients with subluxation had neurologic deficits or required spinal stabilization. Ophthalmologic evaluations demonstrated amblyopia (4 patients) and horizontal strabismus (1 patient), both thought to be coincidental, with no evidence of nystagmus in any case. Seven of the 26 patients required surgical therapy for their neck muscle tightness, while the remainder responded to physiotherapy. Only 2 of the 26 patients underwent cranio-orbital reshaping for correction of their upper face asymmetry. Recognition of cervical subluxation in patients with congenital muscular torticollis may help to explain residual head-neck posturing problems even after successful neck muscle therapy. PMID- 8497519 TI - Assessment of the preferred vertical position of the ear. AB - To determine the most desirable ear level (vertical position), a set of four drawings was assessed by 40 observers. Two levels were almost equally preferred when viewed in profile, one with the upper edge of the ear at the level of the most lateral point of the eyebrow and the other with the upper edge at the height of the upper eyelid. Various factors affecting the visual impression of auricular level and their clinical significance are discussed. PMID- 8497520 TI - The surgical management of orbitofacial dermoids in the pediatric patient. AB - Orbitofacial dermoids in the pediatric population represent a diverse group of lesions. Because of their variability in both clinical presentation and contiguous structure involvement, a thorough understanding of their surgical pathologic anatomy is imperative. In this retrospective review of 84 lesions in 84 patients, we noted segregation of the lesions into three distinct subgroups: brow region dermoids, orbital region dermoids, and nasoglabellar dermoids. Further, we identified physical characteristics within each subgroup that appeared to direct diagnostic workup and subsequent surgical intervention. From this experience, a treatment algorithm was developed that gives the practitioner more precision in the management of these lesions. PMID- 8497521 TI - Hemangiomas, vascular malformations, and lymphovenous malformations: classification and methods of treatment. AB - A total of 207 patients with hemangiomas, vascular malformations, and lymphovenous malformations were treated by the same surgeon from 1980 to 1990. Thirty-seven patients with true hemangiomas underwent surgical treatment. Only those hemangiomas which caused functional or developmental disturbances or those with complications were treated; many more were allowed to regress spontaneously. Sixty-five patients with low-flow and 16 with high-flow vascular malformations were treated by using a variety of surgical approaches. In low-flow lesions, sclerosant therapy can be extremely effective, either alone, in small lesions, or combined with surgical resection or embolization, in larger lesions. Preoperative embolization and surgical excision are the treatment of choice in high-flow malformations. Twenty-seven patients with lymphovenous malformations had only surgical excision with a high success rate. Sixty-two patients with acquired "senile hemangiomas" underwent a single local excision with excellent results. When indicated, angiography has been of great value as a diagnostic procedure to provide information about the vascular dynamics and the extent of these lesions, although magnetic resonance imaging is now being used more frequently for this purpose. Selective angiography also was used as a therapeutic modality when embolization was part of the treatment protocol. A new classification based on clinical, histologic, and vascular flow characteristics of these lesions has been used to simplify the present nomenclature and to help in selection of the most appropriate treatment. It has the added value of being in the language of the radiologist, who should be a member of the vascular anomalies team. PMID- 8497522 TI - Occlusal plane rotation: aesthetic enhancement in mandibular micrognathia. AB - Patients afflicted with extreme degrees of mandibular micrognathia typically have vertically deficient rami as well as sagittally deficient mandibular bodies. This results in deficient posterior facial height, an obtuse gonial angle, excessively steep occlusal and mandibular planes, and a compensatory increase in anterior facial height. The entire maxillomandibular complex is overrotated in a clockwise direction. Standard orthognathic surgical correction fails to address this rotational deformity. As a consequence, the achieved projection of the lower face is inadequate, posterior facial height is further reduced, and occlusal and mandibular planes remain steep. Eleven patients with severe mandibular micrognathia underwent a surgical correction involving occlusal plane rotation to its normal orientation relative to Frankfort horizontal. This was accomplished by Le Fort I osteotomy to shorten the anterior maxilla (creating open bites in seven patients and making preexisting open bites worse in four patients) and sagittal split ramus osteotomies to advance and rotate the mandibular body counterclockwise, thus closing the surgically produced open bite. Counterclockwise rotation of the mandible afforded significantly greater sagittal displacement at the B point (mean 17 mm) than at the first molar (mean 10 mm) and produced adequate degrees of projection of the lower face when accompanied by a modest sliding genioplasty (mean 6.9 mm). Total advancement at the pogonion was a mean of 25.2 mm. In addition, posterior facial height was preserved, and mandibular and occlusal planes were normalized to mean angles of 27 and 10 degrees, respectively. At follow-up, which ranged from 9 to 24 months with a mean of 14.1 months, the mean sagittal relapse at the B point was 1.9 mm. Although heretofore considered unstable and therefore not clinically accepted, maxillomandibular counterclockwise rotation to normalize the occlusal plane rotational deformity provides stable, aesthetically superior results in patients with extreme degrees of mandibular micrognathia. Extended follow-up will be necessary to document long-term stability. PMID- 8497523 TI - Use of the oblique island flap in excision of small facial tumors. AB - Reconstruction with the oblique sigmoid island flap, which we contrived as a subcutaneous pedicle flap, is performed as follows: the small triangular skin flaps, about 1 to 2 mm in length on each side, are excised from both sides of a round defect following tumor excision in a direction corresponding to the wrinkle line, and a subcutaneous island flap which has a width equal to the defect and has shifted about half the distance of the defective area in parallel with the wrinkle line is advanced and sutured. Our technique is thought to be highly effective from a cosmetic point of view because reconstruction of the defects following excision of small tumors that occur in sites with delicate eminence, such as the area between the inner canthal region and the cheek, the site along the nasolabial fold, and around the alae, often tends to fail to achieve cosmetically good results when conventional local skin flaps are used. PMID- 8497524 TI - Lengthening the short nose. AB - Lengthening short nose is one of the most difficult rhinoplasty problems. Two suggestions are made. First, substantial release of soft tissues is mandatory to lengthen the short nose. Second, the technique espoused involves: (1) releasing the septal mucoperichondrium bilaterally, (2) releasing the septal upper from the lower lateral cartilage, and (3) using a baton graft attached to the septum, which in turn holds the tip cartilages in a more caudal position. Thirteen surgeries were performed with satisfactory results and few complications. PMID- 8497525 TI - Intrathoracic free flaps. AB - The utility of pedicled muscle flaps transposed into the thoracic cavity to reconstruct complex intrathoracic defects has been well documented. However, in some patients, local chest-wall muscles have already been either sacrificed or transected by previous thoracotomies and are not available for reconstruction. In these patients, we have successfully employed microvascular techniques to transfer distant muscle flaps into the thoracic cavity. Seven patients with complex intrathoracic defects were reconstructed with three latissimus dorsi, one omental, and three rectus abdominis free flaps. In each case, the microvascular anastomosis was extrathoracic, with the flap transposed into the thoracic cavity. Each of the flaps was revascularized successfully. Four of the five bronchopleural fistulas were sealed, with the remaining patient continuing to demonstrate a reduced but persistent air leak. No infections were encountered, and each flap transfer resulted in a healed wound. When local muscle flaps are not available to reconstruct complex intrathoracic wounds, microvascular transfer of distant muscle flaps can provide abundant well-vascularized tissue for reconstruction of any portion of the thoracic cavity. Versatility is afforded in flap selection and recipient vessel site location, making this technique an important option in the treatment of these difficult wounds. PMID- 8497526 TI - Quantitation of sensibility in gigantomastia and alteration following reduction mammaplasty. AB - A vibrometer and Semmes-Weinstein monofilaments were used to delineate the sensory threshold for quickly and slowly adapting fibers in 13 women with gigantomastia (bra size D or greater) as compared with small-breasted women (bra size A or B). It was found that the mean thresholds for gigantomastia patients were significantly higher (i.e., they were less sensitive) for vibration (p < 0.001) and pressure (p < 0.02). After amputation and free nipple grafting (six patients) or a McKissock-type breast reduction (four patients), six patients had improved sensation, two patients were less sensitive, one patient was unchanged, and one patient was lost to follow-up. These results suggest (1) that preoperatively, there is a chronic traction injury to the fourth, fifth, and sixth intercostal nerves in women with gigantomastia (this is corrected after breast reduction, and sensation improves), (2) that breast reduction surgery itself divides some intercostal nerve fibers, the number dependent on the extent and type of skin and glandular resection (this decreases sensation), and (3) that postoperatively, reinnervation from intercostal and supraclavicular nerves occurs (this improves sensation with time). The postoperative sensory outcome of the breast depends on a combination of these factors; the majority of our patients with gigantomastia have improved sensation after breast reduction. PMID- 8497527 TI - Reduction mammaplasty improves symptoms of macromastia. AB - The condition macromastia has not been defined and characterized precisely by the medical community. Whether the patient with hypertrophic breasts is a candidate for or can be helped by reduction mammaplasty is unclear to both the medical and the lay community. A prospective study of 39 women undergoing reduction mammaplasty surgery was initiated to answer these questions. Patients rated the severity of their somatic pain symptoms and discomfort before reduction mammaplasty and again after complete recovery. The severity of their symptoms and complaints was numerically graded and analyzed. These data were compared with similar data obtained from 40 "small-breasted" women of similar age. Headache, neck pain, back pain, shoulder pain, and bra strap groove pain were present in 60 to 92 percent of patients, and 97 percent of patients had at least three of these pain symptoms preoperatively. All the patients had reduction of their pain symptomatology postoperative, and 25 percent of the study patients had total elimination of pain symptoms by reduction mammaplasty. The postoperative incidence and severity of pain symptoms and discomfort complaints were statistically equivalent to or less than the levels in the control group. PMID- 8497528 TI - Peptide growth factors and myofibroblasts in capsules around human breast implants. AB - Peptide growth factors were mapped immunohistochemically for assessment of their presumed relation to the cells in capsules enveloping gel-filled, smooth-surfaced silicone mammary implants (12 capsules from 11 women). The implant capsules were dominated by fibroblast-like cells, but there were as well macrophages, inflammatory cells, and vascular cells. These cells expressed immunoreactivity for TGF-beta, IGF-II, IGF-I, and, to a lesser extent, PDGFB, NGF, and TNF-alpha. The numerous spindle-shaped cells in the contracted capsules displayed several distinct cytoplasmic actin bundles and fulfilled ultrastructural criteria for myofibroblasts. In contrast, myofibroblasts were recognized in low frequencies in the noncontracted capsules. Mature skin scar tissue did not show any peptide growth factor immunoreactivity, and myofibroblasts were absent. It is postulated that the low-grade chronic inflammatory foreign-body reaction, aggravated by mechanical stress and possible leakage of irritants, stimulates capsule cells to form peptide growth factors, reflecting that extended healing processes prevail in both noncontracted and contracted capsules. We propose that the local enrichment of peptide growth factors, beneficial for acute wound healing, in the chronically irritated tissue around implants provides trophic support for the contractile cells in the implant capsules. PMID- 8497529 TI - The inhibition of fibroblast-populated collagen lattice contraction by human amniotic fluid: a chronologic examination. AB - The effect of human amniotic fluid on fetal wound healing remains to be fully elucidated and may lead to the isolation of factors that could modulate adult wound healing. This study uses an in vitro model of wound contraction, the fibroblast-populated collagen lattice, to examine the effects of chronologically sampled human amniotic fluid on contraction of lattices composed of either human adult or fetal fibroblasts. This chronology has not been reported previously. Human amniotic fluid was obtained in a sterile fashion via amniocentesis from 120 different women at different time points in gestation, ranging from 13 to 24 weeks. At each time point of gestation, three to five samples were individually examined in duplicate sets. Only fluid from pregnancies deemed normal by amniocentesis was included. Contaminated specimens were discarded. Using Bell's protocol, lattices were constructed of acid-soluble rat tail collagen, growth medium, and either human adult fibroblasts or human fetal fibroblasts. Lattices contained 20% v/v human amniotic fluid. In the control lattices, phosphate buffered saline replaced amniotic fluid in equal volumes. Area was measured at 24 hour intervals, and all tests were run in duplicate for each specimen. The mean area at each interval was computed for each gestational week examined. Data were analyzed for significance with ANOVA and Dunnett's t test against control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497530 TI - Vascular prosthetic complications: success of salvage with muscle-flap reconstruction. AB - Prosthetic vascular complications such as exposure and infection represent one of the most challenging and devastating complications in surgery. Nineteen patients underwent a retrospective review of the efficacy of soft-tissue flap coverage in the management of vascular prostheses complications. These patients were divided into three groups. Group 1 included 14 patients with documented culture-positive infection. Group 2 comprised 4 patients with culture-negative exposed grafts. Group 3 included 1 patient with autogenous vein and documented culture-positive infection. The most common vascular procedure requiring flap reconstruction was aortobifemoral in groups 1 and 2. One femoral-distal reconstruction was performed in group 3. Graft complications occurred at an average of 4.8 months after vascular reconstruction in group 1, 11 months in group 2, and 1 month in group 3. Follow-up was obtained on all patients. Initial flap reconstruction was successful in 43 percent of group 1, 100 percent of group 2, and 100 percent of group 3. Reoperative therapy for flap coverage in group 1 was successful in 62.5 percent. Overall, 79 percent of patients obtained a closed wound after reconstructive attempts in group 1. Recurrence appeared to be independent of graft material, microbiology, or graft location. Debridement and muscle coverage of exposed or infected vascular grafts has produced clinical salvage. PMID- 8497531 TI - Preconstruction of the pars pendulans urethrae for phalloplasty in female-to-male transsexuals. AB - One of the goals of phallic construction in female-to-male transsexuals should be the creation of a competent neourethra that allows patients to void while standing. Apart from constructing the perineal fixed part of the neourethra, it is therefore necessary to create a phallus with a pendulant part of the neourethra to be connected to the pars fixa urethrae. In patients in whom we apply microsurgical free-flap techniques for phalloplasty, the pars pendulans is usually created the Chinese way (n = 8). If, on the other hand, pedicled abdominal or inguinal skin flaps are used, a skin-lined urethral tube to be incorporated in the phallus should already be extant in the donor area of the flap (n = 25). In the 20-year period 1971-1991, such a preconstruction of the pars pendulans urethrae has been attempted in 25 female-to-male transsexuals employing Snyder's technique. This has been successful in all and uneventful in 17 patients. If malelike micturition while standing is the goal and the use of microsurgical free-flap techniques is not indicated, this procedure seems to be the method of choice. PMID- 8497532 TI - Comparison of two methods of vagina construction in transsexuals. AB - Twenty-seven male-to-female transsexuals underwent genital transformation. The cosmetic and functional results of 11 vagina constructions using only inverted penile skin were compared with 16 constructions using penile and scrotal skin flaps. Subjective (interview) and objective (physical examination) results are presented. The main conclusions are that vaginal width and subjective evaluation of functional aspects were clearly better after penile and scrotal skin inversion, especially when there was adequate dilatation by the patient. In addition, fewer complications were encountered. Cosmesis was judged better in the penile skin inversion group. PMID- 8497533 TI - Long-term ineffectiveness of suspension material and musculofascial suspensions: a rabbit model. AB - The literature describes various methods of platysma and SMAS modification to enhance rhytidoplasty. This paper evaluates suspension materials: autogenous fascia and dermis, Gore- Tex, and a nylon suture to elevate the panniculus carnosus in a rabbit model using 15 animals. In the second part of this paper, 16 rabbits were used to evaluate imbrication and advancement techniques of the latissimus dorsi muscle. The ineffectiveness of permanently moving a viable, innervated muscle under tension is discussed. PMID- 8497534 TI - What you see is what you get. PMID- 8497535 TI - The nasal lesion: cause celebre for concern. PMID- 8497536 TI - Maxillofacial surgery: past, present, and future. PMID- 8497537 TI - Familial cryptotia. AB - A case of familial cryptotia is presented, and the hereditary basis for this condition is discussed. Although, intuitively, the distribution of the intrinsic auricular muscle, the primary etiologic factor in cryptotia, must be determined genetically, further studies are needed to establish the mode of inheritance. PMID- 8497538 TI - Aesthetic reconstruction of Tikhoff-Linberg shoulder defects with a dual-pedicle TRAM free flap. PMID- 8497539 TI - Unhooking the hook: sculpting the nasal tip by replanting the medial crura. AB - A great challenge of rhinoplasty is the tip with insufficient projection or the hooked nose. Tip grafting is the standard method used to correct this. The open rhinoplasty technique provides exposure of nasal structures not afforded by the closed approach. We have used this approach to sculpt the nasal tip. Successful "unhooking of the hooked nose" by gaining tip projection has been achieved by completely replanting the medial crura. In the operation, the medial crura are freed in their entirety. The lateral alae of the lower cartilages are trimmed. The medial crura are then advanced dorsally until adequate nasal tip projection is obtained. They are secured to each other and to the septum in their new position with interrupted sutures. More tip definition can be obtained, if needed, by suturing the medial crura together near the tip. The dome can be sculpted to an appropriate width in a similar manner. This technique is advantageous because exact symmetry and positioning of the cartilages can be obtained under direct vision. It contours the tip structures to achieve more nasal tip projection, obviating the need for tip grafting. The technique is particularly useful in the patient with a low dorsum and acute nasolabial angle who will benefit from tip augmentation and elevation. The technique simultaneously thins the tip, adds nasal tip projection of 4 to 6 mm, and corrects the nasolabial angle. We have used this technique with good results in 15 patients. The technique and results were illustrated. PMID- 8497540 TI - The lateral arm flap for elbow coverage. AB - A technique for coverage of periolecranon (elbow) defects is presented. The technique uses the local tissues of the lateral upper arm as an axial flap and minimizes the donor defect for this type of reconstruction by obviating the need for a skin graft. PMID- 8497541 TI - Plastic surgery applicants in 1992. AB - All the applicants to plastic surgery residency programs who participated in the residency matching program for 1992 were reviewed. Data were collected on age, sex, race, nationality, place of birth, undergraduate education, medical education, postgraduate training, research activity, and evaluation scores. Findings indicate that applicants interested in academic careers are significantly more likely to have published research and are generally rated higher in categories of intellectual curiosity, performance, and intelligence by evaluators. Women and some minorities were underrepresented when compared with recent medical school graduating classes. We recommend a longitudinal study of applicants to correlate career achievement with applicant characteristics. We also recommend some changes in the application and evaluation process and in efforts to interest women and minorities in the specialty. PMID- 8497542 TI - A new method for clitoroplasty? PMID- 8497543 TI - Deepithelialization in reduction mammaplasty is an anachronism. PMID- 8497544 TI - Primary closure of human bite losses of upper lip. PMID- 8497545 TI - Partial mastectomy. PMID- 8497546 TI - A follow-up on the proximal interphalangeal ear cartilage graft. PMID- 8497547 TI - Identification and location of extravasated silicone gel using magnetic resonance imaging. PMID- 8497548 TI - Plastic surgery: generic or proprietary? PMID- 8497549 TI - Muscle and myocutaneous flaps in rats. PMID- 8497550 TI - Signal-detection outcomes on heartbeat and respiratory resistance detection tasks in male and female subjects. AB - Male and female subjects were compared on heartbeat, respiratory resistance, and light-tone signal-detection tasks. Subjects judged whether a series of 10 tones was coincident with their heartbeats; whether an external load added to the airway was either present or absent during targeted inspiratory cycles; and whether a series of 10 light flashes was matched with auditory tones presented following a fixed delay of either 50 or 100 ms. Nonparametric indices of perceptual sensitivity and response bias indicated that men were more sensitive than women on the resistive load task (p < .05) and on the heartbeat task (p = .07). Performance on the light-tone task was virtually identical. All subjects used a stricter criterion on the respiratory resistance task than on either the heartbeat or the light-tone task; women employed a stricter criterion than men on the heartbeat task. The gender differences may be understood in terms of lateralization of central processing of somesthetic sensory information. PMID- 8497551 TI - Effects of cigarette smoking on electrodermal orienting reflexes to stimulus change and stimulus significance. AB - Skin conductance responses (SCRs) evoked by novel, signal, and frequent tone stimuli were measured in 20 male heavy smokers and 10 male nonsmokers over two sessions. All smokers abstained from smoking for 12 hr prior to each session. Half of the smokers smoked a cigarette of their preferred brand prior to SCR measurement in the first session, whereas the remaining smokers smoked in the second session. Nonsmokers did not smoke. Results combined across the two sessions indicated that abstinence was associated with selective depression of SCRs to the novel tone. Separate analyses of results from each session revealed that, in the second session, SCRs to both novel and signal tones were depressed in abstinent smokers, partially replicating previous findings. By contrast, first session results showed no significant effects of smoking or abstinence. Results were interpreted in terms of nicotine's effects on nonspecific arousal, with some reservations. PMID- 8497552 TI - Postural stability of hemodynamic responses during mental challenge. AB - Laboratory stress testing is typically conducted while subjects are seated, whereas real-life stressors may often be encountered while standing. The present study of 20 healthy young men evaluated blood pressure and underlying hemodynamic adjustments to a standardized mental arithmetic task performed twice while seated and twice while standing. Blood pressure increased during mental arithmetic in both postures, but the underlying hemodynamic determinants of the pressor responses were different for the two postures. Augmented cardiac output was responsible for increasing blood pressure during seated task performance, whereas increased vascular resistance was the mechanism for the pressor response to the task performed while standing. Blood pressure and hemodynamic responses were reproducible subject characteristics for a given posture; test-retest correlations were significant for all cardiovascular measures. However, seated blood pressures responses were not significantly correlated with standing blood pressure responses. In contrast, significant between-posture correlations were found for cardiac output and vascular resistance responses. This preliminary evidence of postural stability of the hemodynamic determinants of blood pressure responses during stress is consistent with growing evidence that hemodynamic response tendencies are robust characteristics of reactivity. Ambulatory monitoring of hemodynamic response patterns during real-life stress may reveal more idiosyncratic profiles of stress reactivity than are displayed by blood pressure responses alone. PMID- 8497553 TI - Cardiovascular activity during mental stress following vigorous exercise in sportsmen and inactive men. AB - Thirty-six competitive sportsmen and 36 inactive men participated in a two session experiment. Session 1 involved exercise to exhaustion so as to assess maximal oxygen consumption (VO2 max). In Session 2, both groups were randomized into three experimental conditions: 20 min of exercise at high intensity (70% VO2max) or moderate intensity (50% VO2max) or a light exercise control. Following 30 min of recovery, all subjects performed mental arithmetic and public speech tasks in a counterbalanced order. Cardiovascular, electrodermal, respiratory, and subjective variables were recorded. Sportsmen had higher VO2max, lower body fat, and lower resting heart rate (HR) than inactive men. A postexercise hypotensive response was observed among subjects in the 70% and 50% VO2max conditions, accompanied by baroreceptor reflex inhibition in the 70% condition. Systolic pressure was lower during mental arithmetic and during recovery from the speech task in the high-intensity than in the control group. Diastolic pressure was lower following mental arithmetic in the high-intensity group. No differences in HR reactivity, electrodermal, or respiratory parameters were observed, but baroreceptor reflex sensitivity was inhibited during mental arithmetic. The results are discussed in relation to previous reports of suppressed cardiovascular reactivity to mental stress tests following vigorous exercise and the role of stress-related processes in the antihypertensive response to physical training. PMID- 8497554 TI - Ongoing ischemic pain as a workload indexed by P3 amplitude and latency in real versus feigned-pain conditions. AB - We tested four independent groups: real pain, real pain/tracking, feigned pain, and feigned pain/tracking. After baseline (auditory oddball task only, .8/.2), the real pain groups had an ischemia cuff applied, which generated intense pain after 14 min. The pain feigners were instructed to simulate pain. The oddball task was repeated during low pain (6 min following cuff application) and during high pain (7-15 min following application). Real pain ratings were affected by low versus high pain and by tracking (reporting pain regularly), which elevated ratings. Nontracking feigned- and real-pain subjects differed in oddball-evoked P3 amplitude and latency during high pain. Oddball P3 amplitude decreased and latency increased from real low pain to high pain. Tracked but not untracked real low pain affected oddball P3 amplitude. Real and feigned pain-tracking subjects did not differ in P3 amplitude. P3 latency differed between real-pain and feigning subjects during low-pain tracking. A 91% individual hit rate (real vs. feign) obtained. PMID- 8497555 TI - Looking at pictures: affective, facial, visceral, and behavioral reactions. AB - Colored photographic pictures that varied widely across the affective dimensions of valence (pleasant-unpleasant) and arousal (excited-calm) were each viewed for a 6-s period while facial electromyographic (zygomatic and corrugator muscle activity) and visceral (heart rate and skin conductance) reactions were measured. Judgments relating to pleasure, arousal, interest, and emotional state were measured, as was choice viewing time. Significant covariation was obtained between (a) facial expression and affective valence judgments and (b) skin conductance magnitude and arousal ratings. Interest ratings and viewing time were also associated with arousal. Although differences due to the subject's gender and cognitive style were obtained, affective responses were largely independent of the personality factors investigated. Response specificity, particularly facial expressiveness, supported the view that specific affects have unique patterns of reactivity. The consistency of the dimensional relationships between evaluative judgments (i.e., pleasure and arousal) and physiological response, however, emphasizes that emotion is fundamentally organized by these motivational parameters. PMID- 8497556 TI - Right hemisphere representation of autonomic conditioning to facial emotional expressions. AB - In this experiment, a lateralized right hemisphere effect was found for electrodermal associative learning to facial emotional expressions. Sixty-two subjects were presented simultaneously with a slide of a happy face in the right or left visual half field (VHF) and a slide of an angry face in the opposite VHF. Four groups were formed by the combination of the two VHF positions of angry/happy faces and the administration/omission of shock unconditioned stimuli. The results showed that simultaneous presentation of the angry face to the right hemisphere and the happy face to the left hemisphere, together with shock, resulted in a strong conditioned association with the angry face and a relatively weak association with the happy face. Furthermore, simultaneous presentation of the angry face to the left hemisphere and the happy face to the right hemisphere, together with shock, resulted in a relatively weak association with both stimuli. No significant differences were found for the no-shock control groups. The present results confirm previous findings of a right hemisphere advantage for representation of associative learning. PMID- 8497557 TI - The psychophysiology of disgust: differentiating negative emotional contexts with facial EMG. AB - The goals of this study were (a) to examine differing views on the relationship between self-report of emotion and physiological expression of emotion, (b) to differentiate between negative emotional contexts during imagery using facial electromyogram (EMG), and (c) to describe the facial muscle patterning and autonomic physiology of situations that involve expelling or avoiding disgusting sensory stimulation. Fifty subjects imagined situations eliciting disgust, anger, pleasure, and joy in 8-s trials using a tone-cued imagery procedure. Heart rate, skin conductance level, and facial EMG at the corrugator, zygomatic, and levator labii superioris/alesque muscle regions were recorded during imagery, and self reports of emotion were collected after imagery trials. Self-reports of emotion produced results consistent with the affective categorization of the images. Activity at the levator labii region was higher during disgust than during anger imagery. Corrugator region increase characterized the negative as compared with the positive emotional contents, and activity at the zygomatic region was higher during joy imagery than during the other three emotions. Heart rate acceleration was greater during disgust, anger, and joy imagery than during pleasant imagery. Disgust imagery could be discriminated from anger imagery using facial EMG, and the expressive physiology of disgust was occasioned by the action set of active avoidance or rejection of sensory stimulation. PMID- 8497558 TI - Intermodal selective attention: evidence for processing in tonotopic auditory fields. AB - Auditory event-related brain potentials (ERPs) were recorded for 250- and 4,000 Hz tone bursts in an intermodal selective attention task. Tonotopic changes were evident in the scalp distribution of the rising phase of the auditory N1 (mean peak latency 116 ms); the N1 was more frontally distributed following the 4,000 Hz than following the 250-Hz tone bursts, and it included a contralateral P90 component that was absent following 250-Hz tones. ERPs related to intermodal selective attention were isolated as negative and positive auditory difference waves (Ndas and Pdas). Neither the Nda nor the Pda showed changes in distribution with tone frequency, but both showed Ear x Frequency changes in distribution. ERPs for deviant tones included mismatch negativities (MMNs) and, in attend auditory conditions, N2b and P3 components. These components did not change in scalp distribution with tone frequency. One possible explanation is that tonotopic displacements of ERP distributions on the scalp surface depend on angular displacements in generator fields on gyral convexities. The results are consistent with the possibility that auditory processing radiates outward with increasing latency from tonotopic fields on Heschl's gyri to more gyrus-free regions of the planun temporale and anterior superior temporal plane. PMID- 8497559 TI - Automated physical activity monitoring: validation and comparison with physiological and self-report measures. AB - Physical activity can be assessed via self-report, via physiological measures such as heart rate and oxygen uptake, or via automated monitor. An electronic accelerometer-based physical activity device (Actigraph) has been reported as an improvement over other activity measurement techniques in terms of utility and accuracy. Four studies provide systematic validation and reliability testing for this device and comparisons with other techniques for assessing daily activities. In the first study, the sensitivity of the Actigraph was determined for differentiating physical activities (walking, running, stair climbing, knee bends) versus sedentary activities (reading, typing, playing video games, and performing a mental arithmetic task). Fifteen healthy adults wore the Actigraph on their wrist during activities; oxygen uptake and heart rate were simultaneously recorded. Results revealed that the Actigraph significantly differentiated between the physical activities (p < .0001) and the sedentary activities (p < .0001). Actigraph counts also correlated significantly with oxygen uptake (r = .73) and heart rate (r = .71) during physical activities (r = .46) and sedentary activities (r = .35), respectively. Test-retest reliability was very high for 12 activities (r = .98). The high level of activity differentiation and strong relationship to oxygen uptake and heart rate suggest the usefulness of this device for behavioral and biomedical studies. However, these studies also indicate that the wrist may not always be the most adequate placement for indexing rate and intensity of daily activities and that further studies are needed to determine the optimal site of monitor attachment. Advantages and disadvantages of self-report, physiological, and automated measures of activity are discussed. PMID- 8497560 TI - Optimal digital filters for long-latency components of the event-related brain potential. AB - A fundamentally important problem for cognitive psychophysiologists is selection of the appropriate off-line digital filter to extract signal from noise in the event-related brain potential (ERP) recorded at the scalp. Investigators in the field typically use a type of finite impulse response (FIR) filter known as moving average or boxcar filter to achieve this end. However, this type of filter can produce significant amplitude diminution and distortion of the shape of the ERP waveform. Thus, there is a need to identify more appropriate filters. In this paper, we compare the performance of another type of FIR filter that, unlike the boxcar filter, is designed with an optimizing algorithm that reduces signal distortion and maximizes signal extraction (referred to here as an optimal FIR filter). We applied several different filters of both types to ERP data containing the P300 component. This comparison revealed that boxcar filters reduced the contribution of high-frequency noise to the ERP but in so doing produced a substantial attenuation of P300 amplitude and, in some cases, substantial distortions of the shape of the waveform, resulting in significant errors in latency estimation. In contrast, the optimal FIR filters preserved P300 amplitude, morphology, and latency and also eliminated high-frequency noise more effectively than did the boxcar filters. The implications of these results for data acquisition and analysis are discussed. PMID- 8497561 TI - Baroreceptor stimulation alters cortical activity. AB - The arterial baroreceptors constitute an essential sensory link for the short term regulation of blood pressure and may also influence higher cortical function. The present study was undertaken to evaluate previous reports of such a cortical influence under conditions of psychologically controlled, mechanical baroreceptor stimulation. This control was achieved by use of PRES (phase-related external suction), a modified neck suction technique. PRES applies short suction bursts that have a different impact on baroreceptors depending on their timing within the cardiac cycle and has the advantage that subjects cannot easily discriminate between conditions of stimulation and inhibition. Electroencephalograms were recorded from 22 subjects during PRES manipulations. A surface-negative shift of about 10 microV developed during the cuff manipulations. Over frontal-central regions, this shift was smaller during baroreceptor stimulation than during inhibition. These data provide support for the proposal that baroreceptor activation influences cortical activity. PMID- 8497562 TI - Public health impact of the 1992 Los Angeles civil unrest. AB - The Los Angeles civil unrest in April 1992 stunned the nation. The days of violence resulted in 53 deaths, 2,325 reported injuries, more than 600 buildings completely destroyed by fire, and approximately $735 million in total damages. The purpose of this paper is to give an overview of the activities of the Public Health Programs and Services Branch of the Los Angeles County Department of Health Services during and after the civil unrest and to illustrate the types of public health issues and problems that may result from large-scale civil disturbance. Public health agencies and jurisdictions should consider these issues in their disaster planning. Public Health Programs and Services Branch activities were directly affected by the violence and destruction. Women, Infants and Children Program vouchering sites and 20 drug program and alcohol recovery sites were damaged or burned and 15 county health centers closed during the unrest. At least 38 private medical and dental offices and 45 pharmacies were destroyed or damaged. County health authorities offered facilities to house relocated private care providers and filled prescriptions for medications where needed. The environmental health impact required the inspection of 2,827 burned and damaged sites for hazardous waste including asbestos; at 9 percent of the inspected sites, waste required special disposal. More than 1,000 food facilities suffered damage and required inspection before reopening. In the 3 months following the unrest, a 20-percent increase in disposal capacity was authorized at four county landfills to accommodate the disposal of debris. Violence was a public health issue of particular concern. The Centers for Disease Control and Prevention sent a team to study the violence from an epidemiologic perspective. The Federal agency also provided funding for televised children's talk shows dealing with reactions to the violence. PMID- 8497563 TI - Maintaining confidentiality in a look-back investigation of patients treated by a HIV-infected dentist. AB - The spread of human immunodeficiency virus (HIV) from a Florida dentist with acquired immunodeficiency syndrome (AIDS) to several of his patients has generated considerable concern about the risk of HIV transmission during dental treatment. Accordingly, self-reporting of HIV infection and subsequent AIDS by a dentist at our medical center prompted notification and testing of patients at risk. Key features of the notification and testing process were (a) only patients who had undergone procedures deemed to pose appreciable risk of exposure to the dentist's blood were notified, (b) the identity of the dentist was shielded by not including in notification letters any identifying information other than the name of the medical center, and (c) patients' blood specimens were tested promptly for HIV antibodies and results were reported immediately to each patient to minimize the period of anxiety. HIV antibody testing was requested by 41 of the 88 patients to whom notification letters were sent, and all 41 were HIV negative after having undergone 395 procedures by the HIV-infected dentist. Review of the 88 patients' medical and dental records showed that at least 77 had received treatment by other health care providers at the medical center so that they would not be able to ascertain which provider had HIV infection. None of the patients who were notified by the medical center subsequently queried the dentist concerning possible HIV infection. Our experience demonstrates that look-back investigations can be conducted by institutions in a manner that substantially protects the identity of health care workers with HIV infection, minimizes the number of patients discomfitted, and avoids excessive utilization of personnel time. Even greater protection of the identity of health care workers with HIV infection presumably can be achieved when notification is undertaken by a public health agency. PMID- 8497564 TI - Secular trends in New York City hospital discharge diagnoses of congenital syphilis and cocaine dependence, 1982-88. AB - The ecologic relationship between the incidence of reactive serologic tests for syphilis among 2,229 newborns and diagnoses that included cocaine dependence among 17,219 hospitalized women ages 15-44 in New York City was investigated. Citywide, race-specific and zip code-specific annual rates were computed. The residential zip codes were grouped into quartiles by cumulative level of diagnoses that included cocaine dependence, and citywide and race-specific annual rates of congenital syphilis were computed in each quartile. From 1982 to 1988, the citywide rate of congenital syphilis for all races increased from 1.2 to 5.8 per 1,000 live births, while rates of cocaine dependence discharges increased from 23.3 to 423.3 per 100,000 women of all races during the same period. For African American infants, citywide rates of congenital syphilis increased from 1.8 to 10.6 per 1,000 live births. In quartile-specific analyses of African American women and newborns, rates of congenital syphilis increased from 1.9 to 14.6 in the highest cocaine-exposure quartile; from 2.1 to 12.4 in the third; from 1.5 to 7.6 in the second; and, from 1.6 to 2.8 in the lowest cocaine exposure quartile. This study provides support for the hypothesis that cocaine dependence in women may be associated with congenital syphilis infection. PMID- 8497565 TI - Planning community-wide services for persons with HIV infection in an area of moderate incidence. AB - The human immunodeficiency virus (HIV) epidemic has placed enormous strains on health care and social services delivery. The authors studied the response to the epidemic by a local health jurisdiction in an area of moderate incidence. The area recorded about 1,000 cumulative cases of acquired immunodeficiency virus syndrome, and the estimated prevalence of HIV infection was 10,000 as of 1991. The local health jurisdiction combined methods in a community-wide planning process for HIV services. The process mobilized the existing community-based network of service providers to identify problem areas and to develop recommendations for action. The planning group used questionnaires and service use rates to project service requirements, estimate service availability, and establish levels of unmet needs in terms of units of service. Annual requirements per person with HIV infection were projected for case management (0.3 to 0.4 client enrollment slots), dental care (1.9 to 3.4 visits), nonacute institutional care (1.2 days), home health care (17.8 to 22.1 visits), short-term housing (8.3 to 10.6 days), mental health and emotional support (34.6 to 36.6 visits), legal services (2.7 appointments), acute inpatient medical care (2.0 to 3.2 days), and inpatient psychiatric care (0.2 to 0.3 days). Those service requirement estimates for a low or moderate HIV incidence area may be transferable to other communities. PMID- 8497566 TI - Where injecting drug users receive HIV counseling and testing. AB - In 1990, nearly 1.5 million human immunodeficiency virus (HIV) antibody tests were performed at publicly funded sites. Eight percent of those tests were performed for self-identified illegal injecting drug users (IDU). The authors examined data from 28 project areas using a client record data base that permitted an analysis of self-reported risk behavior by type of service delivery site. Among self-identified IDUs, 68 percent of those tested and 82 percent of those found to be seropositive had obtained HIV counseling and testing services in settings other than drug treatment centers. The findings indicate that HIV prevention programs for IDUs need to be available in various service delivery settings, not just in drug treatment programs. Strong links and cooperation between sites offering HIV counseling and testing and sites providing drug treatment programs are important to preventing HIV transmission to and from IDUs. PMID- 8497567 TI - Directions for AIDS education for Hispanic women based on analyses of survey findings. AB - In 1988 and again in 1990, the National Center for Health Statistics conducted a survey of the AIDS related knowledge and beliefs of Hispanic and non-Hispanic adults in the United States. A survey of Los Angeles Hispanic women was conducted in 1990, using the 1988 survey instrument. This study is an examination of the trends in knowledge and beliefs by comparing those of Hispanic Los Angeles women in 1990 to Hispanic and non-Hispanic female respondents in the 1988 national sample. Despite intense public health, local community, and media efforts to educate the public about AIDS, the women in the Los Angeles sample did not show appreciable differences in knowledge and beliefs compared with the 1988 national sample, and in many areas they were less knowledgeable. These results may be related to differing education and acculturation levels as well as possible differences in ethnicity. Hispanic groups will need focused prevention efforts which take into account specific areas of knowledge, educational level of information, adherence to traditional beliefs and practices, and ethnicity of the targeted community. PMID- 8497568 TI - Results of a 29-state survey of tuberculosis in nursing homes and correctional facilities. AB - A survey of the 15,379 cases of tuberculosis reported to the Centers for Disease Control and Prevention by 29 State health departments in 1984 and 1985 revealed that 7.7 percent of the victims older than age 64 were living in a nursing home at the time of diagnosis and 1.8 percent between the ages of 15 and 64 were living in a correctional institution at the time of diagnosis. Incidence rates of tuberculosis for residents of nursing homes and for inmates of Federal and State prisons and local jails were estimated using denominators derived from institutional population counts provided by the National Center for Health Statistics and by the Department of Justice, Bureau of Justice Statistics, and Bureau of Prisons. The aggregate tuberculosis incidence rate for nursing home residents in the 29 States was 1.8 times higher than the rate seen in elderly persons who were living in the community (95 percent confidence interval on the relative risk 1.64, 2.02). The aggregate tuberculosis incidence rate for inmates in correctional facilities was 3.9 times higher than the rate for persons of a similar age who were not incarcerated (95 percent confidence interval on the relative risk 3.35, 4.49). Strengths and limitations of the design and implications of the first survey of tuberculosis incidence, in a large number of States, among residents of nursing homes and correctional facilities are discussed. PMID- 8497569 TI - Disability and cognitive impairment are risk factors for pneumonia-related mortality in older adults. AB - The role of functional and cognitive limitations in the risk of pneumonia-related mortality in older adults was examined. As part of a cohort study in 3 communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA), 6,234 women and 4,035 men ages 65 or older completed baseline interviews between 1981 and 1983 and were followed for up to 6 years. Sex-specific Cox proportional-hazards regression models were used to examine the association of baseline physical and cognitive functioning with report of pneumonia (ICD9 480 486) as an underlying, immediate, or contributing cause of death. During followup, a total of 243 men and 160 women died with pneumonia. Adjusting for age, race, education, evidence of five chronic diseases, and smoking status, a significantly increased risk of pneumonia mortality (P < 0.05) was found for limitations in activities of daily living and cognitive impairment among both men and women. Inability to walk a half mile, climb stairs, or perform heavy housework was significantly associated with increased risk of pneumonia mortality for women but not for men in the same multivariate models. Men and women whose body-mass index was above the median had significantly lower risk of pneumonia mortality compared with those in the lowest quartile. Further elucidation of the sequence between physical and cognitive impairment and risk of pneumonia will be important in reducing pneumonia-associated morbidity and mortality. PMID- 8497570 TI - The emergency department in surveillance of attempted suicide: findings and methodologic considerations. AB - The authors conducted one of the first active, population-based public health surveillance systems for detecting suicide attempts in the United States. Surveillance was conducted in all four hospital emergency departments serving a county suburban to Atlanta, GA, with a population of 426,000. Emergency department staff gathered information from all patients who presented with an intentionally self-inflicted injury (suicide attempt) or with thoughts about self injury (suicidal ideation). During an 18-month period in 1988 and 1989, 798 suicide attempt-related patients were reported, for a rate of 124.7 per 100,000 county residents per year. Females had a higher attempted suicide rate than males, but males had a higher completed suicide rate. Ingestion of drugs or poison was the most common method of attempted suicide (71.1 percent), and use of firearms was the most common method of completed suicide (69.8 percent). In comparing reported cases with those found by reviewing emergency department log books, the authors found that the case reports were 58 percent complete and that surveillance reporting was highly representative of all cases requiring emergency transport. The authors conclude that emergency department-based surveillance for attempted suicide is feasible. It can provide representative data that may be used to monitor trends in attempted suicide and to define high-risk groups. Such surveillance may also allow timely detection of suicide attempt clusters, facilitating prompt intervention. PMID- 8497571 TI - The University of Maryland experience in integrating preventive medicine into the clinical medicine curriculum. AB - Lifestyle risk factors play a major role in the etiology of premature mortality, morbidity, and disability in the United States. Numerous professional groups as well as the Surgeon General of the Public Health Service have recommended that increased attention be devoted to training medical students and physicians to improve their knowledge and skills in health promotion and disease prevention. Such training is critical for attaining many of the "Healthy People 2000" objectives. For a variety of reasons, however, most medical schools have had difficulty in successfully integrating preventive medicine into their clinical curriculums. This article describes the critical elements that allowed the faculty at the University of Maryland School of Medicine to accomplish this goal through its fourth year clinical preventive medicine course. The strategies employed in this course may serve as a model for other institutions to achieve the integration of preventive medicine into their clinical curriculums. PMID- 8497572 TI - Fatal incident risk factors in recreational boating in Ohio. AB - To identify risk factors predicting the involvement of boat operators in incidents resulting in at least one fatality, the authors obtained data from a mail survey of registered boat owners in the State of Ohio and from the Boating Accident Report (BAR) files for 1983-86 compiled by the Ohio Department of Natural Resources. Additionally, they reviewed Ohio death certificates for those years to identify cases missed by the BAR system. Forty percent of the fatal incidents would have been missed by a search of death certificates alone. During the period studied, 107 boating incidents resulted in 124 deaths. There were 0.9 fatal incidents per million boat-operator hours. Factors found to be associated with an increased risk of a fatal boating incident were the operator being younger than 30 years, having fewer than 20 hours of boat operating experience, and lacking formal boat safety training. Canoes, kayaks, rowboats, and inflatables were associated with a higher rate of fatal incidents per million hours of use than were motorboats. Young age and lack of experience were associated independently with increased risk, explaining some of the effects associated with types of boats and with lack of training. The findings suggest that supervised experience, safety training programs aimed at young operators, and interventions specific to certain types of boats are likely to reduce boating fatalities. PMID- 8497573 TI - Risk factors for drowning and near-drowning among children in Hillsborough County, Florida. AB - The authors obtained data from 700 households in Hillsborough County, FL, in a telephone random survey to determine risk factors for incidents of drowning and near-drowning among children in the county. The survey was conducted from August through December 1991. A combination of forced-choice and open-ended questions was used to assess adults' drowning-related knowledge, attitudes, and prevention behaviors, as well as the incidence of and the circumstances surrounding drowning and near-drowning among children who lived in those households. The results showed that although most respondents had some knowledge of the epidemiology of drowning and near-drowning among children, deficits were noted in their knowledge of the importance of adult supervision and the recommended age at which to begin children's swimming instruction. Results showed a need for isolation fencing, that which separates a swimming pool from a house and yard. Most respondents reported that they did not know how to perform cardiopulmonary resuscitation (CPR) on an infant or child. More than 40 percent reported not knowing how to perform CPR on an adult. Respondents reported no drowning or near-drowning incidents among children of their household within the last 3 years. However, the respondents did describe water-related immersions that involved children who experienced difficulty in the water, but recovered by themselves or with the aid of a nearby person. In some instances the child's breathing pattern was altered. There were three episodes during which difficulty in breathing occurred. The respondents reported a total of nine childhood water-immersion episodes within their families, none of which had been reported to treatment facilities. Recommendations are provided for programs for prevention of childhood drowning. PMID- 8497574 TI - Designing prenatal care messages for low-income Mexican women. AB - Communication theories and research data were used to design cross-cultural health education messages. A University of California Los Angeles-Universidad Autonoma in Tijuana, Mexico, research team used the methods of ethnographic and survey research to study behaviors, attitudes, and knowledge concerning prenatal care of a sample of pregnant low-income women living in Tijuana. This audience provided information that served as a framework for a series of messages to increase awareness and change prenatal care behaviors. The message design process was guided by persuasion theories that included Petty and Caccioppo's elaboration likelihood model, McGuire's persuasion matrix, and Bandura's social learning theory. The results from the research showed that poor women in Tijuana tend to delay or not seek prenatal care. They were not aware of symptoms that could warn of pregnancy complications. Their responses also revealed pregnant women's culturally specific beliefs and behaviors regarding pregnancy. After examination of these and other results from the study, prenatal care messages about four topics were identified as the most relevant to communicate to this audience: health services use, the mother's weight gain, nutrition and anemia, and symptoms of high-risk complications during pregnancy. A poster, a calendar, a brochure, and two radio songs were produced and pretested in focus groups with low-income women in Tijuana. Each medium included one or more messages addressing informational, attitudinal, or behavioral needs, or all three, of the target population. PMID- 8497575 TI - Ethnicity, maternal risk, and birth weight among Hispanics in Massachusetts, 1987 89. AB - National data reveal that low birth weight and infant mortality rates among Hispanics are, in general, between the rates for whites and those for blacks. The question remains, do differences in low birth weight reflect distributions of known risk factors, or do ethnic differences persist after simultaneously adjusting for intervening variables? In this study, Massachusetts birth certificate data for 206,973 white non-Hispanic infants and 19,571 Hispanic infants are used to examine differences in low birth weight between white non Hispanic and Hispanic infants, as well as variation among seven subgroups of Hispanic mothers--Puerto Rican, Dominican, Central American, South American, Mexican, Cuban, and other Hispanic. Regression analysis is used to estimate the association between risk factors and birth weight and the relative risk of low birth weight. Risk factors include ethnicity, demographic characteristics, biological factors, access to prenatal care, and infants' conditions. Results indicate substantial variation in mean birth weight, low birth weight, and levels of risk among Hispanic subgroups and between Hispanics and white non-Hispanics. Puerto Rican infants had the lowest mean birth weight and, in general, the highest level of risk factors in this population. None of the adjusted odds ratios for low birth weight for any Hispanic group was significantly elevated at the 95 percent level compared with white non-Hispanics. Findings in this study confirm the previous observations of the wide variation among Hispanic subgroups and the high level of risk among Puerto Ricans. Results of this study also raise some interesting questions about the differential relationship between ethnicity and birth weight, ethnicity and low birth weight, and the significance of maternal place of birth as a proxy measure of adaptation or acculturation. PMID- 8497576 TI - Effects of enhanced calling efforts on response rates, estimates of health behavior, and costs in a telephone health survey using random-digit dialing. AB - Public health researchers frequently rely on random-digit dialing (RDD) telephone surveys in monitoring trends in health behavior and evaluating health promotion interventions. RDD response rates have declined during the past decade, and cost effective methods to increase response rates are needed. The authors evaluated two levels of enhanced calling efforts in an RDD survey of cancer-related health behavior in the State of Washington. The first level of enhanced calling effort was 1 month after 11 original calling attempts to a household, when the authors attempted up to 11 recalls. The second level was 6 months after the first answered call, when the authors recalled those persons who could not be interviewed. Enhanced calling efforts increased the overall survey response rate by 11 percent. Nine percentage points of the increase were attributable to call backs. There were demographic differences among the participants reached at different levels of calling effort, but no consistent associations of level of calling effort with health behavior related to alcohol use, smoking, diet, or health screening. Marginal costs for interviews completed with enhanced calling efforts were about 50 percent higher than costs for interviews reached in the first 11 calls. The authors concluded that enhanced calling efforts may be justified, because they increase confidence in the generalizability of survey results. However, the authors found very little change in survey results by including interviews from persons who were difficult to reach and to interview. PMID- 8497577 TI - Adjusting for nonresponse bias in a health examination survey. AB - There is a potential for nonresponse bias in most population studies using health examinations. This is true of the Mexican American portion of the Hispanic Health and Nutrition Examination Survey (HHANES), conducted by the National Center for Health Statistics, in which unit nonresponse to the examination accounted for 24 percent of the sample. Even though the full effect of nonresponse can never be really known, ancillary information from the interview sample can be used in an attempt to adjust for bias in estimates. Two techniques for nonresponse bias adjustment are presented and illustrated using health status level and hypertension status from published studies based on the HHANES of 1982-84. The first approach uses conditional probabilities and the second approach uses direct standardization. The examples examine whether or not an adjustment for socioeconomic status, sex, and age--variables related to both response status and the conditions under study--changes the prevalence estimates of (a) Mexican Americans who report poor, fair, or good health status and (b) hypertension among Mexican Americans. PMID- 8497578 TI - Social support in smoking cessation among black women in Chicago public housing. AB - To accomplish significant reductions in smoking by the year 2000, special populations with relatively low rates of smoking cessation must be reached and helped to quit smoking. These populations are most often groups in which traditional approaches to smoking cessation have not been successful. Focus groups were conducted with black women who were residents of Chicago public housing developments. The purposes were to assess factors related to smoking and the women's willingness to participate in cessation programs. The findings reveal several barriers to smoking cessation. These barriers are linked to the difficult daily existence and environment of these women and to a lack of social support that would help them to achieve smoking cessation. The barriers include (a) managing their lives in highly stressful environments, (b) major isolation within these environments, (c) smoking as a pleasure attainable with very limited financial resources, (d) perceived minimal health risks of smoking, (e) commonality of smoking in their communities, (f) scarcity of information about the process of cessation available to them, and (g) belief that all they need is the determination to quit on their own. The women emphasized that smoking cessation would be more relevant to them if part of broader social support efforts geared to improve their lives. The public health system may need to consider such strategies to engage this group of women. PMID- 8497579 TI - Benefits of collecting local data on breast cancer and mammography practices in northwestern Pennsylvania. AB - The use of local data on cancer incidence and mortality and on risk-related behaviors to help communities set priorities and guide program planning is an important facet of the National Cancer Institute's Program, "Data-Based Intervention Research for Public Health Agencies." As a participant in this program, the Pennsylvania Department of Health has developed a "breast cancer profile" for a seven-county, predominantly rural region of northwestern Pennsylvania. Community hospitals in the area are collaborating with the health department to develop interventions to enhance screening mammography. The availability of the profiles allowed hospitals to compare local breast cancer risk and screening activities with those of the State and nation, to target interventions, and to establish a baseline to measure changes over time. The data generated great interest among health professionals in northwestern Pennsylvania because, contrary to their expectations, the region was quite similar to the State and nation. While the proportion of women ages 40 and older who had ever had a mammogram was relatively high (66 percent), the proportion with more than one mammogram was considerably lower (43 percent), suggesting that hospitals focus on promoting regular mammography. Although it is feasible to develop data based interventions for local areas, the effort is not trivial. State and national agencies must cooperate to ensure comparability of data collection and reports so that comparisons of local, State, and national data can be produced routinely. PMID- 8497580 TI - Questioning the safety of food irradiation. PMID- 8497581 TI - Mortality patterns among the youth of a northeastern American Indian cohort. AB - Mortality patterns prevalent among American Indian youth have not been well documented. This investigation reports on mortality patterns among the Seneca Nation of Indians from January 1, 1955, through December 31, 1989. The study cohort consisted of 3,033 Seneca tribal members born during the study period. Deaths occurring among cohort members younger than age 25 were identified through a computer match against New York State vital record files. Sex-specific standardized mortality ratios were calculated on the basis of mortality patterns exhibited by the general population of New York State, exclusive of New York City. Males exhibited significantly elevated mortality for all causes combined, for deaths due to all accidents combined, for motor vehicle accidents, and for suicide. Females demonstrated significantly elevated mortality from all accidents combined, for motor vehicle accidents, and for all other types of accidents. Age specific mortality patterns also varied both by sex and by calendar time. These findings are important to consider in the design of programs aimed at reducing premature mortality among American Indian populations from preventable causes of death. PMID- 8497583 TI - HHS sets up national HIV-AIDS consultation by telephone. PMID- 8497582 TI - NIMH prevention research helps women change AIDS risk behavior. PMID- 8497584 TI - Pediatric HIV infection in its second decade--the changing pattern of lung involvement. Clinical, plain film, and computed tomographic findings. AB - The changing pattern of pediatric HIV infection is illustrated in this article with plain films and computed tomographic scans. Today, vertical transmission from infected mothers results in HIV infection of exposed infants in about one third of pregnancies. Although the high mortality with catastrophic illnesses such as Pneumocystis carinii pneumonia seen in early life appears to be decreasing, chronic illness with pulmonary involvement due to diffuse lymphocytic infiltrative syndromes continues. Lymphocytic interstitial pneumonitis (LIP) has evolved in some patients to cystic lung disease and bronchiectasis. There are increasing numbers of patients infected with Mycobacterium. Masses seemingly of smooth muscle origin, thought to be leiomyosarcoma are appearing; they may be pseudotumors related to concomitant Mycobacterium avium intracellulare infection. PMID- 8497585 TI - Transplantation and the pediatric chest. AB - The plain chest radiograph is the mainstay in the imaging assessment of the chest in a prospective organ recipient and is invaluable in the initial evaluation of posttransplant complications. Although the presence of focal or diffuse air-space disease on a chest radiograph is often nonspecific, this finding helps direct the choice of other diagnostic methods. Among cross-sectional imaging techniques, computed tomography is used most often to further define anatomy and abnormal findings and to guide needle biopsy or aspiration if necessary. A variety of posttransplant complications are discussed, including common postoperative findings, pulmonary infection, and organ rejection. PMID- 8497586 TI - Nuclear medicine in the pediatric chest. AB - Nuclear medicine enables functional evaluation of organ systems not possible with standard anatomic imaging modalities. The pathophysiology necessitating scintigraphic examination of the pediatric patient is often different from that in the adult and therefore calls for new or modified applications of nuclear medicine. This article briefly reviews such application, with the scope limited to the evaluation of the pediatric chest and organ systems. PMID- 8497587 TI - Perinatal and postnatal chest sonography. AB - Sonography is the primary method used to image the fetal chest. Many significant congenital anomalies such as pleural effusion, congenital diaphragmatic hernia, cystic adenomatoid malformation, pulmonary sequestration, and congenital heart disease can be detected during early prenatal sonography. Fetal sonography also permits accurate assessment of the severity of these processes, allowing for parental counseling and optimal planning of postnatal care. After birth, sonography is the primary method for evaluating cardiac anatomy and diagnosing congenital heart disease. Sonography also serves as a useful adjunct to plain film radiology and other modalities in evaluation of the mediastinum, diaphragm, pleura, and chest wall. PMID- 8497588 TI - Sonography of the chest in children. AB - Sonography is an extremely important tool in the evaluation of the chest in children. Its easy availability, versatility, and portability make it an obvious choice as the next diagnostic examination after an abnormal chest radiograph. Patience and meticulous technique coupled with good anatomic knowledge will produce useful studies. Sonography is equivalent and sometimes superior to CT because of its Doppler ability and superior fluid and tissue characterization. It is most helpful in the assessment of anterior and middle mediastinal masses, opaque chest, and pleural and juxta-diaphragmatic abnormalities; in the classification of perplexing radiographs; and in the assessment of peripheral chest lesions. Sonography provides guidance for diagnostic and therapeutic aspiration, providing not only excellent anatomic demonstration, tissue characterization, and vascular information but also immediate access to bacteriologic and tissue diagnosis when required. PMID- 8497589 TI - High-resolution computed tomography of pediatric pulmonary parenchymal disorders. AB - The role of CT in the diagnosis of pediatric lung disease is still evolving, but certain indications are already well established. In immunocompromised or other high-risk children who have fevers or respiratory symptoms but normal or nonspecific chest radiographs, HRCT can detect and localize disease, thus allowing earlier therapy. It also has been shown that HRCT can assess the severity of disease in bronchiectasis and cystic fibrosis and that it may provide a more sensitive means of evaluating therapy in these conditions. Areas for research include the effects of infection on the developing lung, quantification of bronchopulmonary dysplasia, the prevalence of complications in asthma, and the use of HRCT in pulmonary edema of all types. As CT scan times decrease, the use of CT will expand to younger, sicker, and less cooperative children. Dynamic scanning probably will develop to provide a more accurate assessment of the focal and generalized air trapping that accompanies many common pediatric diseases. PMID- 8497590 TI - Magnetic resonance of congenital cardiovascular disease. An update. AB - Magnetic resonance (MR) has become an important tool in the evaluation of the child who has congenital heart disease. Current techniques and applications of MR in the evaluation of great vessels, vascular causes of airway obstruction, and the postoperative patient are discussed. PMID- 8497591 TI - Telltale signs of congenital heart disease. AB - There are several key plain film findings that raise suspicion for and aid in the differentiation of congenital heart defects. These 'telltale' signs and their significance and the additional necessary imaging studies of cardiac lesions are discussed with particular emphasis on the role of magnetic resonance imaging. PMID- 8497592 TI - Imaging of mediastinal masses in children. AB - Conventional radiographs show the mediastinum to be the most frequent location of thoracic masses in children. The compartmental approach to evaluation of pediatric mediastinal masses is advised. Compartmental localization and lesion internal characteristics are best determined by cross-sectional imaging techniques. These techniques as well as the causes and significance of the common pediatric mediastinal masses are discussed. Imaging of the thymus is emphasized because normal thymic tissue can mimic pathologic conditions and the thymus is a common thoracic location for neoplasms in children. PMID- 8497593 TI - Diseases of the trachea, bronchi, and smaller airways. AB - Except in the fetus, life depends on the integrity of the airways. This article describes ways in which that integrity can be threatened in childhood. PMID- 8497594 TI - Cystic fibrosis. Clinical update for radiologists. AB - The clinical features and current management of cystic fibrosis are reviewed, with emphasis on pulmonary manifestations. Pulmonary radiographic findings in cystic fibrosis are illustrated. The role of transplantation as a therapeutic avenue is discussed. Recent discoveries--the specific genetic mutation in cystic fibrosis, the elucidation of the cellular defect, and the development of gene transfer techniques to correct the cellular defect in vitro--have generated fresh excitement in the search for an ultimate cure for cystic fibrosis. PMID- 8497595 TI - Cysts and cystlike lesions of the lung. AB - This article has reviewed the major pulmonary cystic lesions occurring in infants and children. The chest radiograph will initially reveal either single or multiple well-circumscribed radiopaque or radiolucent areas. In younger patients, radiopaque lesions are best evaluated with sonography, which can define the internal architecture of the mass, its location, and vascular supply. On the other hand, radiolucent lesions, lesions inaccessible to the sonographic beam, and lesions requiring analysis of the pulmonary parenchyma are best assessed with CT. MR is helpful in the preoperative evaluation of sequestration after infancy. Thus within the framework of an age-dependent algorithm, pulmonary cystic lesions can be analyzed effectively and an appropriate diagnosis established. PMID- 8497596 TI - Nodules, masses, and pseudomasses in the pediatric lung. AB - The vast majority of pulmonary masses in children are nonmalignant. Most pediatric nodular disease is granulomatous in origin. Infections and congenital lesions outnumber neoplastic lesions. Pulmonary metastatic disease most often results from Wilms' tumor and is followed in frequency by the sarcomas. Primary pulmonary malignancy is rare in the child. PMID- 8497597 TI - The newborn chest. AB - Newer therapeutic techniques in the respiratory management of preterm and full term neonates have resulted in improved survival, particularly in those infants who have respiratory distress syndrome, severe pneumonia, and surgical lesions of the chest. Although respiratory distress syndrome is being seen less frequently because of improved ventilatory management and the use of surfactant replacement therapy, the increased survival of preterm infants has resulted in an increased incidence of bronchopulmonary dysplasia, still a frequently seen pulmonary abnormality. Children who have severe pulmonary disease related to diaphragmatic hernia, meconium aspiration pneumonia, and infectious pneumonia are treated with extracorporeal membrane oxygenation, resulting in a higher survival rate and better outcome. Other abnormalities of the lung, including pneumonia, are seen in both preterm and full-term infants, have characteristic radiographic appearances, and require prompt antibiotic treatment. PMID- 8497598 TI - Radiology, surgery, and the pediatric chest. AB - Preoperative imaging of the tracheobronchial tree should focus on identifying the location, severity, and extent of tracheal narrowing, as well as possible causes of extrinsic compression. Plain film radiography and esophagography can be supplemented with CT or MR imaging for the evaluation of mediastinal masses or vascular abnormalities impinging on the airway. Surgical planning for the removal of intrathoracic tumors or cysts requires a detailed evaluation of the location and extent of the lesion, identification of encasement or compression of vital structures, and intraspinal extension to determine resectability and the need for neurosurgical consultation. Precise preoperative histologic diagnosis in most patients is not essential for surgical planning. Although the anatomic information provided by CT and MR imaging is comparable, MR offers the advantage of multiple imaging planes and allows the identification of intraspinal involvement of posterior mediastinal tumors or neuroenteric cysts without the use of intrathecal contrast agents. Conversely, MR imaging has little role in the assessment of pulmonary parenchymal abnormalities. These are best imaged with radiography and CT. Plain film radiography and contrast esophagography are often sufficient for the identification and delineation of postoperative complications in the chest. Complex air or fluid collections, however, may require further study with CT or ultrasonography for better characterization. PMID- 8497599 TI - Intervention in the thorax in children. AB - The 1970s and 1980s have been a period of significant growth and innovation in interventional radiology. Interventional procedures that were developed and perfected with adult patients are now being used very successfully in pediatric patients. In comparison with surgical management, interventional procedures generally have lower morbidity and mortality, require shorter hospital stays, and are less expensive. Preprocedural imaging and planning, adequate monitoring and sedation during the procedure, and selection of equipment appropriate for pediatric patients maximizes the chance for a successful outcome. PMID- 8497600 TI - Imaging the postoperative neck. AB - The variety of cervical lymphadenectomy and neck reconstructive procedures that have been developed in the past 20 years has led to confusion about nomenclature in the literature. In addition, some of these operations result in gross alteration of the normal anatomy. The authors review the present classification system for cervical lymph nodes and various lymphadenectomy and reconstructive procedures. Examples of typical postoperative images are given. A protocol for postoperative follow-up is presented, which calls for imaging for 5 years after surgery. Finally, the authors review their experience with 400 cases, 276 of which were initially classified as having no clinical evidence of disease. Recurrence developed in 68 of these (in 62 [91%] within 4-18 months of surgery). Imaging findings altered the postoperative salvage plan in 17 (25%). Clinically occult disease was found at sectional imaging in 47 (17%). PMID- 8497601 TI - Orbital rhabdomyosarcoma: a paradigm for irradiation. PMID- 8497602 TI - Breast imaging and the standard of care for the symptomatic patient. PMID- 8497603 TI - MR imaging of patients with intracranial aneurysm clips. PMID- 8497604 TI - MR angiography versus conventional X-ray angiography in the lower extremities: everyone wins. PMID- 8497605 TI - Percutaneous femoropopliteal graft placement: is this the next step? PMID- 8497606 TI - In vivo microscopy of hepatic tumors in animal models: a dynamic investigation of blood supply to hepatic metastases. AB - The dynamics of blood circulation in three experimental animal models of hepatic metastasis were investigated with in vivo microscopy. It was demonstrated that the tumor vasculature communicated with the portal venules and hepatic sinusoids that surrounded the tumors. The hepatic artery was not seen to connect to the tumors directly. However, it was demonstrated that arterial blood entered tumors through the portal venules and that the hepatic arterial flow entered the tumor without resistance, while blood from the portal vein met great resistance at the tumor border, with only small amounts entering the tumor. Interruption of either the hepatic artery or the portal vein did not result in cessation of the blood circulation in hepatic tumors. A reciprocal relationship between the hepatic arterial and portal venous supplies to hepatic tumors was suggested, and it was hypothesized that arterioportal communications play an important role in the arterial and portal venous supply of blood to hepatic tumors. A comprehensive understanding of the blood supply of hepatic tumors is important for improving clinical treatment of hepatic tumors. PMID- 8497607 TI - Symptomatic peripheral vascular disease: selection of imaging parameters and clinical evaluation with MR angiography. AB - In the first phase of this study, seven healthy subjects underwent examination with two-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography to develop a protocol for evaluation of peripheral arterial vasculature from the infrarenal aorta to the foot. In the second phase, 73 patients with symptomatic peripheral vascular disease underwent examination with both conventional contrast material-enhanced arteriography and two-dimensional TOF MR angiography to evaluate the clinical usefulness of MR angiography. Postinterventional and intraoperative angiography or direct surgical exploration was the standard of reference. In 32 patients, discrepancies occurred between findings on arteriograms and those on MR angiograms; most of these discrepancies were caused by improved depiction of runoff vessels on MR angiograms. The demonstration with MR angiography of blood vessels not seen on conventional arteriograms, unidentified stenoses, or misidentified blood vessels altered surgical management in 12 patients (16%). Metal-clip artifacts obscured clinically important disease on MR angiograms in two patients. It is concluded that two-dimensional TOF MR angiography is very useful in preoperative assessment of patients with severe peripheral vascular disease. PMID- 8497608 TI - Atherosclerotic occlusive disease of the lower extremity: prospective evaluation with two-dimensional time-of-flight MR angiography. AB - A prospective, blinded comparison of two-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography and conventional arteriography was performed in 25 patients who underwent routine arteriography for symptomatic atherosclerotic occlusive disease of the lower extremity. MR angiography was performed from the distal abdominal aorta through the popliteal trifurcation. The native arterial tree was divided into nine segments; each segment was assessed for patency (defined as stenosis < 50% of arterial diameter), moderate stenosis (50%-69%), severe stenosis (70%-99%), or occlusion (100%). In all 206 segments examined, the sensitivity of MR angiography in diagnosis of occlusion was 100%; the specificity, 98%. All long occlusions were correctly classified. In specific categories of occlusive disease, the sensitivity and specificity were as follows: in all segments with 70% or greater stenosis, including occlusions, 90% and 97%; in all segments with 50% or greater stenosis, including occlusions, 92% and 88%; in femoropopliteal segments with 50% or greater stenosis, 92% and 93%; and in iliac segments, 93% and 83%. Long occlusions were distinguished from short occlusions and stenoses; hence, MR angiography enabled identification of patients with lesions suitable for angioplasty. PMID- 8497609 TI - Percutaneous femoropopliteal graft placement. AB - Femoropopliteal bypass surgery is now recommended for the treatment of long segment or diffuse superficial femoral artery disease. The authors describe a technique for percutaneous placement of a prosthetic femoropopliteal graft. The technique has been accomplished with conventional polytetrafluoroethylene graft material and a variety of implantation techniques. Technical success was achieved in eight patients who underwent graft placement. Grafts up to 28 cm in length were placed, and graft patency was demonstrated up to 6 months after implantation. Six of the eight patients were asymptomatic during the follow-up period; one patient who had symptoms during this time underwent thrombolysis and redilation of the distal stent, and the symptoms resolved. This study demonstrates the feasibility of percutaneous graft placement in the femoral artery, but durability must be established in relation to traditional bypass surgery before it can be recommended on a wider scale. PMID- 8497610 TI - Percutaneous retrieval of nonvascular foreign bodies. AB - Although intravascular foreign bodies are routinely removed with percutaneous extraction, surgical retrieval is performed of most nonvascular foreign bodies. The authors describe six cases in which percutaneous extraction was performed for removal of nonvascular foreign bodies. These foreign bodies included an intraabdominal laparotomy towel, two pelvic drains, an angiographic guidewire fragment in a pelvic abscess cavity, and a superficially located sewing needle and bullet fragment. Computed tomography or plain radiography was performed to define the safest track for percutaneous removal. Fluoroscopy was performed to direct foreign body removal; the major challenge of the procedure was precise localization of the foreign body to minimize dissection. Although a surgeon and operating suite were available for backup care if necessary, all six foreign bodies were removed successfully without complication by the interventional radiologist in the radiology suite. Percutaneous retrieval of nonvascular foreign bodies, while not frequently performed, can in many cases obviate surgical incisions, extensive dissection, and the cost and risk of administration of general anesthesia. PMID- 8497611 TI - Automated biopsy devices: a blinded evaluation. AB - To evaluate 20 different automated biopsy devices with respect to the quality of tissue obtained for histopathologic analysis, a total of 1,470 18-gauge biopsy specimens were obtained from 10 fresh autopsy cases, including 30 liver, 20 kidney, 10 pancreas, and 10 psoas muscle biopsy specimens per device and per biopsy depth. There was no statistical difference in the performance of the long throw Biopty, ASAP 18, 1.9-cm UltraCut, long-throw Monopty, and 2.5-cm ABS biopsy guns. All obtained a large amount of tissue with minimal fragmentation or crush artifact. Most of the short-throw biopsy guns (depth of biopsy < or = 1.1 cm) did not perform as well. Although the other guns performed adequately, less than optimal results were obtained with the Temno, Bio-Gun, Roth, Klear Kut, ABC, and Urocut biopsy guns. Most 18-gauge automated biopsy devices with a biopsy excursion of at least 2.0 cm provide a high-quality, diagnostically adequate specimen for histopathologic analysis. PMID- 8497612 TI - Self-expanding stent in the treatment of benign esophageal strictures: experimental study in pigs and presentation of clinical cases. AB - The reaction of the normal esophageal wall to inserted self-expanding nitinol stents was studied in pigs. An inflammatory reaction with increasing fibrotic activity and degeneration of the muscular layers in the esophageal wall was demonstrated. Five patients with severe dysphagia secondary to benign esophageal strictures also underwent insertion of self-expanding nitinol stents. All of the stents expanded completely, with subsequent regression of dysphagia. One treated esophagus was resected and showed deep implantation of the stent meshwork in the esophageal wall. Significant stenoses secondary to tissue hyperplasia, located at the edges of the stent, occurred in two patients. These results show that self expanding nitinol stents may be used for palliation of dysphagia in patients with benign esophageal strictures. Because of the observed reactions in the esophageal wall, such treatment should be restricted to selected patients until more experience has been gained. PMID- 8497613 TI - Gastrostomy conversion to transgastric jejunostomy: technical problems, causes of failure, and proposed solutions in 63 patients. AB - Sixty-three radiologically guided conversions of gastrostomy to transgastric jejunostomy performed over a 4-year period were reviewed. Conversions succeeded in 31 of 38 surgically placed gastrostomies (82%), in 14 of 18 endoscopically placed gastrostomies (78%), and in seven of seven radiologically placed gastrostomies, for an overall success rate of 83%. Almost all failures (10 of 11 gastrostomies) were primarily the result of unfavorable fundal angulation of the surgical or endoscopic tract; unfavorable angulation was also the most common technical problem encountered in the successful conversions. Of the 52 successful conversions, 23 (44%) necessitated tube replacement: eight for spontaneous proximal migration of the tube, 11 for accidental tube dislodgment, and four for tube blockage. While most gastrostomy to transgastric jejunostomy conversions are simple to perform, in many cases the unfavorable angle of the original transcutaneous tract precludes jejunal intubation and may be a cause for early recoil of a successfully placed jejunal catheter back into the stomach. With early recognition of an unfavorable tract, a fresh transgastric jejunostomy through a new, properly angled puncture may be the preferred approach. PMID- 8497614 TI - Treatment of pancreatic pseudocysts with percutaneous drainage and octreotide. Work in progress. AB - In an attempt to decrease catheter drainage of pancreatic pseudocysts, a combined regimen of percutaneous drainage and administration of octreotide acetate was used in eight symptomatic patients. Indications for the combined therapy were pseudocyst recurrence (four patients), pancreatic fistula from percutaneous drainage (two patients), or elective treatment to restrict pancreatic drainage. Octreotide acetate was administered subcutaneously in doses of 50-1,000 micrograms three times a day. The drug was well tolerated and produced only limited adverse effects in four patients: pain at the injection site, hypoglycemia, diarrhea, headaches, and lower-extremity edema (more than one adverse effect was experienced by each patient). The combined use of percutaneous drainage and administration of octreotide was effective in seven patients and failed in one patient who had distal pancreatic duct occlusion. In five patients, catheter drainage decreased to no measurable amount by a mean of 13.8 days. These results suggest octreotide is effective in decreasing the output from pancreatic pseudocysts drained percutaneously. PMID- 8497615 TI - Early-enhancing pseudolesion in medial segment of left hepatic lobe detected with multisection dynamic MR. AB - On multisection dynamic magnetic resonance (MR) images obtained in the arterial dominant phase, the authors have occasionally noted the presence of an early enhancing pseudolesion, which is not a hypervascular tumor, in the medial segment of the left hepatic lobe. Multisection dynamic MR imaging was performed in 185 patients with suspected liver disease. A suspect early-enhancing pseudolesion was present in six of the 185 patients. In all six patients, the pseudolesion was located in the subcapsular portion adjacent to the porta hepatis in the medial segment of the left hepatic lobe. Corroborative and follow-up studies failed to demonstrate any evidence of a pathologic condition, therefore justifying the term "pseudolesion." Radiologists should be aware of the possibility of the presence of this early-enhancing pseudolesion in this typical location on multisection dynamic MR images, because such a finding may be misinterpreted as a true lesion. PMID- 8497616 TI - A new macromolecule as a contrast agent for MR angiography: preparation, properties, and animal studies. AB - The authors developed and evaluated a polymer as a contrast agent for magnetic resonance (MR) angiography. The agent consists of a monomethoxy ether of poly(ethylene glycol) covalently attached to poly(L-lysine) (PL), with PL serving as the carrier of gadolinium diethylenetriaminepentaacetic acid (DTPA). Immunogenicity and toxicity studies were performed in mice, and biokinetic and metabolic studies were performed in rats. Dose response studies were performed with a three-dimensional time-of-flight sequence in eight rats. No permanent immune response was elicited against Gd-DTPA or the carrier molecule, and accumulation in organs of the reiculoendothelial system was minimal. The blood half-life of the agent was 14 hours. A dose of 20 mumol of gadolinium per kilogram of body weight was sufficient to increase the vessel-muscle ratio by four- to fivefold. Contrast was substantially improved and remained unchanged 2 hours after contrast medium administration, and good visualization of four orders of vasculature was allowed. PMID- 8497617 TI - Sustained uterine contractions: a cause of hypointense myometrial bulging. AB - Fifteen pregnant women were studied with magnetic resonance (MR) imaging. In 14 women, the myometrium exhibited distinct hypointense bulging on T2-weighted images that distorted the gestational sac and decidua but not the outer uterine coutour. In 12 women, an obvious discrepancy was observed between the inner myometrial configuration on T1-weighted images and that on intermediate and T2 weighted images. In three women who underwent serial T2-weighted studies separated by about 30 minutes during one MR examination, hypointense myometrial bulging was observed at a different site on each study. In two women who underwent follow-up MR study within a week after dilation and curettage, the previously distinct hypointense bulging completely disappeared. These findings confirm the transient and mobile nature of this myometrial bulging. This phenomenon can be attributed to sustained uterine contractions, which partially force the blood out of the uterus. The decrease in blood volume results in a decrease in water content, which accounts for the decrease in myometrial signal intensity on T2-weighted images. PMID- 8497618 TI - Varicoceles: postoperative prevalence--a prospective study with color Doppler US. AB - To define the ultrasound (US) prevalence of varicoceles after surgical repair, 28 postoperative patients underwent color Doppler US. A group of 26 control subjects also underwent color Doppler US to establish the prevalence of varicoceles in the healthy population. Eighteen of 28 (64%) patients who underwent color Doppler US scanning 16.4 months, on average, after varicocele repair had evidence of a varicocele, a number similar to that reported in other series for infertile men before surgery. Dominant veins in the postoperative patients were larger (P < .01) than those in the control subjects. Postoperative improvements in sperm parameters and conception rate in our subjects were 58% and 43%, respectively, consistent with findings reported in the literature. The prevalence of varicoceles detected at color Doppler US in our healthy population was 42% (11 of 26). Physical examination after surgery failed to show a varicocele in 20 of 22 (91%) patients examined. The discrepancy between sperm parameters and the results of color Doppler US and physical examination raises questions about the utility of US as a means of evaluation in the postvaricocelectomy patient. PMID- 8497619 TI - Predictive value of image-guided adrenal biopsy: analysis of results of 101 biopsies. AB - A retrospective study of 97 patients undergoing 101 image-guided adrenal biopsies (IGABs) was performed to analyze the effects of specific pathologic results on test characteristics. Three categories of pathologic results (benign adrenal tissue, malignant tissue, and nondiagnostic) were compared with outcomes. Diagnostic samples were obtained in 86% of cases. Among 72 patients with proved outcomes, IGAB had an accuracy of 96%, a sensitivity of 93%, and a negative predictive value of 91% (92% in patients with bronchogenic carcinoma). In this subset of patients, 33 had biopsy specimens that contained benign adrenal tissue. In these 33 patients, three masses (each smaller than 3 cm) proved malignant. In the 14 patients with nondiagnostic samples, two masses proved malignant. Obtaining benign adrenal tissue was highly predictive of benignity, even in the setting of lung cancer. The authors conclude that IGAB is an accurate procedure in both oncologic and nononcologic patients. However, when the biopsy specimen does not contain benign adrenal tissue or malignant cells, repeat percutaneous biopsy or surgery should be considered. PMID- 8497620 TI - Human coronary arteries: projection angiograms reconstructed from breath-hold two dimensional MR images. AB - The authors sought to render projection magnetic resonance (MR) angiograms depicting a substantial length of human coronary arteries from sequential breath hold two-dimensional MR images. Tomographic images of the right and left anterior descending coronary arteries were collected with use of a segmented gradient recalled sequence that incorporated fat suppression and prone positioning of the patient over a surface coil. After editing the images to eliminate overlapping chamber signals and after realigning the images, a maximum-intensity-projection algorithm was applied to create projection angiograms. For the 10 coronary arteries without severe narrowing, visualized length with projection MR angiography was 109 mm +/- 29 (mean +/- standard error of estimate) versus 121 mm +/- 29 with conventional coronary angiography (ranges, 62-147 mm and 70-180 mm, respectively). At conventional angiography linear regression indicated vessel length to be 1.03 times the length depicted at MR angiography with good correlation (r = .8). Results indicate good correlation between measurements of vessel length with both conventional and MR angiography. PMID- 8497621 TI - Arrhythmogenic right ventricular dysplasia: evaluation with electron-beam CT. AB - The authors evaluated four cases of arrhythmogenic right ventricular dysplasia (ARVD) with electron-beam computed tomography (CT). Except for magnetic resonance imaging, non-invasive imaging techniques such as two-dimensional echocardiography and radionuclide angiography cannot always depict the abnormal morphology of the right ventricle. Definite diagnosis of ARVD requires the use of invasive cardiac cineangiography. Proper identification of right ventricular involvement in ARVD with CT helps in the diagnosis. Volume-mode CT clearly depicted an enlarged right ventricle with a scalloped surface of the free wall, conspicuous trabeculations with low attenuation, and abundant epicardial adipose tissue, which are characteristics of ARVD. Cinemode CT revealed reduced right ventricle function and abnormal wall motion. The authors propose that millisecond-order, electron beam CT is a suitable noninvasive examination for evaluating the morphologic characteristics of the right ventricle and its function in ARVD. PMID- 8497622 TI - Interventional radiologists: occupational radiation doses and risks. AB - Interventional radiologists receive nonuniform occupational radiation doses, with relatively high doses to the head and extremities and low doses to the trunk, which is protected by a lead apron. Twenty-eight interventional radiologists from 17 institutions wore thermoluminescent dosimeters over their collars and under their aprons for a 2-month period. The estimated annual radiation dose was converted to effective dose as suggested by the International Commission on Radiological Protection. Effective dose is used to relate the risk associated with nonuniform dose to that associated with an equivalent uniform whole-body dose. The mean annual effective dose was 3.16 mSv (316 mrem), with a range of 0.37-10.1 mSv. The mean annual effective dose is approximately equal to the mean natural background dose of 3 mSv per year from radon and other natural sources and is only 6% of the National Council on Radiation Protection and Measurements' recommended effective dose equivalent limit of 50 mSv per year. The annual radiation risk of fatal cancer would be less than one per 10,000 for almost the entire career of an interventional radiologist. PMID- 8497623 TI - Cavernous hemangiomas: dipolar susceptibility artifacts at MR imaging. AB - A misleading susceptibility artifact was originally encountered at magnetic resonance imaging in a patient with multiple cavernous hemangiomas. By using a gradient-recalled echo sequence, the artifact appeared on axial sections as a single ring of enhanced signal intensity within the expected signal void around many of the individual lesions. It was hypothesized and confirmed through phantom experiments with ferromagnetic samples that hemosiderin deposits within each lesion behaved like a point magnetic dipole, causing the intravoxel signal interference patterns that appeared as a ring of enhanced signal intensity. The artifact was therefore found to be entirely susceptibility-induced. Knowledge of the origin and appearance of this new artifact will aid radiologists in the interpretation of susceptibility images and help them avoid misinterpreting a single lesion as multiple contiguous lesions. PMID- 8497624 TI - Evaluation of breast masses and axillary lymph nodes with [F-18] 2-deoxy-2-fluoro D-glucose PET. AB - Twenty-eight patients with a total of 35 suspect breast masses underwent positron emission tomography (PET) with [fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG) in order to study the utility of this technique in the evaluation of breast cancer. FDG PET allowed discrimination between eight benign and 27 malignant breast masses, with a sensitivity of 96% and specificity of 100%. Among the malignancies, there was a significant correlation between normalized FDG uptake and nuclear grade (P = .006). In addition, the results of PET imaging were compared with results of axillary node dissection in 20 cases of breast cancer. PET allowed correct categorization of 10 of 10 axillae as negative (specificity = 100%). PET results were equivocal in one axilla and positive in the remaining nine of 10 axillae with positive dissection results (sensitivity = 90%). The authors conclude that FDG PET may give useful information on breast masses and axillary node status prior to surgery. PMID- 8497625 TI - Tumor recurrence versus fibrosis in the irradiated breast: differentiation with dynamic gadolinium-enhanced MR imaging. AB - To assess the value of magnetic resonance (MR) imaging of the breast in the differentiation of late postirradiation fibrosis from recurrent carcinoma, 35 women with a history of breast carcinoma treated conservatively with radiation therapy underwent MR imaging. Nine patients had recurrent tumors confirmed at biopsy and surgery. Twenty-six patients had a localized fibrotic mass confirmed at biopsy and/or during long-term clinical and radiologic follow-up. In all cases, a localized hypointense area was present on plain spin-echo T1-weighted images. In all recurrent tumors, dynamic gadolinium-enhanced T1-weighted images demonstrated early increased signal intensity of the lesion within 3 minutes after bolus injection. The signal intensity over time in localized fibrosis differed from that in tumor recurrence, with no substantial enhancement on post contrast T1-weighted images. Short inversion time inversion recovery and spin echo T2-weighted images were not useful in the differential diagnosis of recurrent tumor versus radiation fibrosis. PMID- 8497626 TI - Silicone implant rupture: detection with US. AB - The authors evaluated the ability of ultrasound (US) in detection of silicone implant ruptures and compared US detection with that of mammography and physical examination in 22 women with 29 sites of implant leakage. On sonograms, leaks were evident from a highly echogenic pattern of scattered and reverberating echoes with loss of detail posterior to the echogenic area. The area appears as a "snowstorm" and has a well-defined anterior margin but a poorly defined posterior margin. Twenty-five sites in 19 women were surgically confirmed. Mammograms obtained with various views and sonograms were available for comparison in 20 of 25 surgically confirmed leaks. Of all 29 leaks, 14 were detected at physical examination as palpable masses. Six of these 20 leaks were not detected with mammography. With US, only one leak was not detected. US allowed more accurate prediction of the extent of free silicone in the breast and enabled detection of silicone within axillary nodes. Recognition of the characteristic highly echogenic sonographic appearance of microglobules of free silicone in the soft tissues can improve detection of implant rupture. PMID- 8497627 TI - Utility of axillary views in postmastectomy patients. AB - This study was performed to determine the utility of routine axillary radiography in postmastectomy patients. The records of 185 postmastectomy patients who had undergone axillary radiography were retrospectively reviewed. Of 499 views obtained, only 10 (2%) were reported as abnormal. Only one of the 10 patients with abnormal studies had a demonstrated recurrence that corresponded to the mammographic finding. This patient also had positive physical examination results at that time. Eight of the 185 patients developed local recurrences, four of which were in the axilla of the affected side. These four cases were all detected at physical examination; two patients underwent relatively concurrent axillary radiography. One of these two patients with abnormal physical examination results had a positive axillary view obtained in the same month. The other of these two patients with abnormal physical examination results had a negative axillary view obtained 3 months earlier. The authors conclude that routine axillary radiography is not useful in postmastectomy patients. PMID- 8497628 TI - Mammography film-labeling practices. AB - The labeling practices of 390 facilities that consecutively submitted screening mammography images (mediolateral oblique and craniocaudal views) to the American College of Radiology (ACR) Mammography Accreditation Program over a 2-month period were evaluated. Methods for identifying the patient and facility included a flash card at 333 facilities (85%), stick-on paper labels at 54 (14%), and handwriting directly on the film at three (1%). Identification labels included the patient's first and last name at 372 facilities (95%), the date at 370 (95%), the name of the facility at 349 (89%), a unique patient identification number at 328 (84%), the patient's age at 169 (43%), the name of the referring physician at 146 (37%), and the patient's date of birth at 129 (33%). Labeling practices, information provided, and methods used varied considerably from one site to another. Adoption of ACR guidelines for labeling mammography films is encouraged. PMID- 8497629 TI - Atypical mycobacterial infection in the lung: CT appearance. AB - The author examined computed tomographic (CT) scans of the chest from 40 patients with cultures positive for atypical mycobacteria. Common manifestations included bronchiectasis, air-space disease, nodules, and scarring and/or volume loss. Less commonly observed signs were cavities, lymphadenopathy, and pleural disease. Serial scans were obtained in 10 patients and showed new areas of bronchiectasis and progression of existing bronchiectasis, suggesting that the bronchiectasis was not a preexisting condition but resulted from infection. The anatomic distribution of the above findings was diffuse, not strongly favoring any lung zone. The identification of multifocal coexistent bronchiectasis, air-space disease, and nodules at CT should raise the possibility of atypical mycobacterial lung disease, even in an otherwise healthy patient. PMID- 8497630 TI - Radiologic evaluation of the intravenous oxygenator. AB - This report describes the radiologic appearance of the intravenous oxygenator (IVOX), an intracorporeal CO2-O2 exchanger for use in patients with severe respiratory deficiency, and the extensive radiographic and sonographic support required for its use. Six patients aged 19-39 years who had severe adult respiratory distress syndrome (ARDS) and who were not expected to survive were selected for IVOX placement; ARDS was caused by trauma (four patients), severe pneumonia (one patient), or a fat embolus from a tibial fracture (one patient). Before insertion of the IVOX, all patients underwent evaluation of their right internal jugular vein, right common femoral vein, and inferior vena cava with real-time ultrasound (US) to ascertain vascular size. The IVOX improved oxygenation in all patients; because of such improvement, one patient survived. Use of the IVOX may become common; hence, radiologists should understand how the IVOX functions and its appropriate placement, be able to identify it on chest and abdominal radiographs, and appreciate the importance of US in placement of this device and follow-up. PMID- 8497631 TI - Desquamative interstitial pneumonia: thin-section CT findings in 22 patients. AB - To evaluate the findings on thin-section computed tomographic (CT) scans in desquamative interstitial pneumonia (DIP), the CT scans from 22 patients aged 22 71 years (mean age, 43 years) were reviewed. In all patients, DIP was proved with open-lung biopsy performed 1 day to 17 months before or after examination with CT (median interval, 1.5 months). The lungs were divided into three zones (upper, middle, and lower); each zone was evaluated separately. The predominant finding was the presence of areas of ground-glass attenuation that involved the middle and lower lung zones in all patients and the upper lung zones in 18 patients (82%). Such areas had a lower lung zone predominance in 16 patients (73%) and a predominantly peripheral distribution in 13 patients (59%). Irregular lines of attenuation suggestive of fibrosis were seen in 11 patients (50%) and cystic changes, in seven patients (32%). The distribution of abnormalities in DIP is similar to that seen in usual interstitial pneumonia (UIP), but the greater extent of ground-glass attenuation and the paucity of cystic changes in DIP should enable distinction from UIP in most patients. PMID- 8497632 TI - Pneumoconiosis: comparison of digitized and conventional radiographs. AB - The classification of pneumoconiosis on 108 paired radiographs obtained in coal miners was compared by using conventional radiograph film images and digitized images of those conventional film images. Conventional film images and digitized images were each independently read in a random order in two separate sessions by three radiologists certified as "B" readers. Overall, the digitized images were perceived as being of better quality than the conventional film images (radiograph quality grade 1, 48% [617 of 1,292 classifications] vs 37% [482 of 1,296], respectively; P < .001). The mean International Labour Office (ILO) scores for small-opacity profusion were similar between the digitized images and conventional film images (3.14 vs 3.24, respectively; P = .19). The mean absolute differences in small-opacity profusion score between radiograph pairs were also similar (0.74 vs 0.77, respectively; P = .50). No difference in the ILO type of opacity was noted between the display modes. Interpretation of digitized images for pneumoconiotic small opacities was shown to be an acceptable alternative to interpretation of conventional film images; the important problem of reader variability affects both display modes. PMID- 8497633 TI - Pulmonary intravascular tumor emboli: dilated and beaded peripheral pulmonary arteries at CT. AB - The diagnosis of pulmonary intravascular tumor emboli is difficult to establish both clinically and on conventional radiographic studies. Between 1985 and 1991, four cases of pulmonary intravascular metastases were demonstrated on computed tomographic (CT) scans from among 14,000 CT scans of the chest. A retrospective study of these cases was performed, including a review of chest radiographs. All four patients had invasive tumors, including an atrial myxoma, a renal cell carcinoma, an osteosarcoma, and a chondrosarcoma of the pelvis. Three cases had histopathologic documentation of pulmonary artery tumor emboli. At CT, all the patients demonstrated multifocal dilatation and beading of peripheral pulmonary arteries, primarily in a subsegmental distribution involving multiple lobes. Ossification of the pulmonary arteries occurred in one case of metastatic osteosarcoma. In two cases, small, peripheral wedge-shaped opacities distal to some abnormal pulmonary arteries suggested pulmonary infarcts. The finding of dilated and beaded peripheral pulmonary arteries at CT is highly suggestive of metastatic intravascular tumor emboli. PMID- 8497634 TI - Bladder capacity as measured at voiding cystourethrography in children: relationship to toilet training and frequency of micturition. AB - To assess the reliability of a frequently used formula for calculating bladder capacity in children, bladder capacity was measured prospectively at voiding cystourethrography in 274 consecutive healthy infants and children. Bladder volume index (BVI) was then calculated by dividing the measured capacity by the predicted capacity. Bladder capacity increased dramatically after 18 months and reached a plateau between 3 and 4 months of age, after which there was no further significant increase in capacity until approximately 9 years. BVI abruptly increased from 1.03 in children aged less than 18 months to 1.50-1.60 in children aged between 18 months and 4 years (P < or = .0001). Because bladder capacity increases sharply during infancy and early childhood and levels off once toilet training is complete, linear models used to predict bladder capacity on the basis of age alone significantly underestimate bladder capacity in infants and younger children. PMID- 8497635 TI - Pediatric lung transplantation: radiographic-histopathologic correlation. AB - Chest radiographic and histopathologic findings were retrospectively reviewed to determine the spectrum of findings in 16 children who underwent a total of 19 lung transplantations. Radiographs were evaluated for air-space disease, interstitial disease, Kerley B lines, pleural fluid, and cardiac size, and the interval from transplantation to the onset of complications was determined. Radiographic findings were correlated with 62 histopathologic diagnoses obtained from 51 transbronchial and open lung biopsy specimens. The final histopathologic diagnoses were acute rejection (n = 19), chronic rejection (n = 8), infection (n = 11), lymphoproliferative disorder (n = 4), and nonspecific (n = 20). The radiographic patterns of the complications were not significantly different. Seventy-nine percent (15 of 19) of episodes of acute rejection and 64% (seven of 11) of episodes of infection occurred within 5 weeks of transplantation, while 63% (five of eight) of the episodes of chronic rejection occurred after this period. Since chest radiographs are nonspecific, caution should be exercised in basing clinical decisions only on the radiographic pattern in the absence of corroborative clinical and histopathologic findings. PMID- 8497636 TI - Subtle orthopedic fractures: teleradiology workstation versus film interpretation. AB - The purpose of this study was to evaluate whether radiologists perform equally well with plain radiographs or digitized images displayed on a video monitor in interpretation of difficult orthopedic trauma cases. Interpretations with film and those made from a teleradiology system with spatial resolution of 2.35 line pairs per millimeter were compared in 120 difficult cases, 60 with the selected abnormality (ie, fracture or dislocation) and 60 that were control cases. Seven senior radiology residents and one radiology fellow each interpreted 60 randomly ordered cases with the teleradiology system (1,280 x 1,024-pixel monitors) and 60 cases with the original radiographs. The overall accuracy of the readers was 80.6% for film interpretations and 59.6% for teleradiology screen readings (P < .001). Sensitivity was 78.5% for film and 48.8% for on-screen images (P < .001), and specificity was 83.2% for film and 72.3% for on-screen images (P < .025). Receiver operating characteristic analysis showed rejection of the null hypothesis in favor of film interpretation (P < .0049). It was concluded that the teleradiology system was not acceptable for primary diagnostic interpretation of difficult fracture cases. PMID- 8497637 TI - Anterior translocation of the tibia at MR imaging: a secondary sign of anterior cruciate ligament tear. AB - The authors evaluated measurement of the degree of anterior subluxation ("translocation") of the tibia in regard to the femur as a predictor of anterior cruciate ligament (ACL) tear. Eighty-nine magnetic resonance (MR) imaging studies of patients with either an arthroscopically confirmed intact (n = 29), acutely torn (n = 27), or chronically torn (n = 33) ACL were retrospectively reviewed. The degree of translocation was measured on hard-copy images by using two methods. Buckling of the posterior cruciate ligament (PCL) was also evaluated. Anterior tibial translocation, when measured at the midsagittal plane of the lateral femoral condyle with regard to a plane parallel to the cephalocaudal axis of the image, was a relatively specific indicator of ACL disruption. Subluxation of 5 mm or more had 58% sensitivity, 93% specificity, and 69% accuracy for an ACL tear. All knees with subluxation of 7 mm or more had torn ACLs. Buckling of the PCL was less sensitive and less accurate than anterior translocation as an indicator of ACL disruption. PMID- 8497638 TI - Fracture of the posterior aspect of the lateral tibial plateau: radiographic sign of anterior cruciate ligament tear. AB - Plain radiographs obtained in 25 patients with acute anterior cruciate ligament (ACL) tears detected with magnetic resonance imaging were retrospectively evaluated to identify associated bone lesions. Fracture of the posterior part of the lateral tibial plateau (LTP) was seen in 11 patients, impacted fracture of the lateral femoral condyle (LFC) in two, lateral tibial rim fracture (Segond fracture) in three, and avulsion fracture of the tibial attachment of the ACL in two. The latter three fractures have been associated with an ACL tear. Conversely, fractures of the posterior part of the LTP have not been associated with ACL tear and are recognizable on plain radiographs. Impaction of the LFC on the LTP and avulsion of the posterior tibial capsular junction may account for the association of the fracture of the LTP with the acute ACL tear. This type of fracture represents the most frequent indirect sign of ACL tear seen on plain radiographs. PMID- 8497639 TI - MR imaging of meniscal tears: narrow versus conventional window width photography. AB - Narrow window width photography of magnetic resonance (MR) images of knee menisci is promoted as a useful tool in the detection of meniscal tears. To assess the diagnostic efficacy of this method, conventional and narrow window width MR images of 48 patients (96 menisci, 37 tears) were interpreted by two experienced observers. Images were graded on a five-point scale to enable receiver operating characteristic (ROC) curve analysis. The ROC curves constructed from the conventional window width interpretations were similar to those of the narrow window width interpretations for both observers. It was not possible to prove that the areas under the two curves were significantly different. This suggests that there is no globally significant improvement in the detection of meniscal tears when narrow window width images are used for interpretation. PMID- 8497640 TI - Rheumatoid arthritis: evaluation of wrist extensor tendons with clinical examination versus MR imaging--a preliminary report. AB - To determine whether magnetic resonance (MR) imaging can improve assessment of the extensor tendons of the wrist and their propensity to rupture, the dorsal tendons in 23 wrists in 20 patients with rheumatoid arthritis were clinically assessed and then examined with MR imaging. Clinical and MR imaging evaluations were performed blindly and independently. The six extensor tendon compartments were assessed with MR imaging for presence of pannus, synovial effusion, and tendon involvement or rupture. Clinical scores of systemic disease, dorsal tendon sheath swelling, and risk of tendon rupture ranged from 0 to 3 in each category; the overall score was not associated with any MR imaging category. Clinical assessment of enlargement of the dorsal tendon sheath and clinical risk of rupture correlated poorly with findings on MR images. All eight wrists with clinically minimal risk of rupture had pannus, effusions, and tendon involvement on MR images; the findings were similar in the wrists with moderate (grade 2) risk of rupture. MR imaging depicts involvement of the dorsal tendon sheath and dorsal tendons that cannot be assessed with other radiologic or clinical means. PMID- 8497641 TI - Diuretic-enhanced I-131 clearance after ablation therapy for differentiated thyroid cancer. AB - The authors assessed whether the whole-body radiation burden can be reduced with diuretic enhancement of iodine-131 excretion in patients with thyroid cancer and slow clearance. Whole-body imaging and quantitative I-131 clearance data obtained before and after ablation therapy were evaluated in 56 patients. Fourteen patients with slow pre-ablation therapy clearance (> 50% retention at 24 hours) received oral diuretics after I-131 therapy. Nine patients began taking furosemide 24 hours after I-131 treatment. Five patients had been receiving thiazide diuretics and were continued on the same dose after treatment. The mean half-time of I-131 clearance for the patients treated with furosemide decreased by 12 hours (P < .05) but was not significantly decreased for those who received thiazides or for the patients who did not receive diuretics. Administration of diuretics can improve I-131 clearance in patients with thyroid cancer and slow clearance, reducing the radiation burden and shortening the hospital stay. PMID- 8497642 TI - Radiation therapy of pituitary adenoma: delayed sequelae. AB - Clinical records and follow-up computed tomographic (CT) scans were reviewed for 134 pituitary adenoma patients who underwent radiation therapy between 1970 and 1988, to determine the long-term clinical and radiologic complication rates for patients treated in a fairly standard manner for nonmalignant disease. The group consisted of 82 males and 52 females aged 16-85 years (median, 46 years). Fifty nine (44%) of the 134 tumors were secretory. One hundred eighteen patients underwent surgical resection and radiation therapy, and 16 underwent only primary radiation therapy. Ninety-seven percent (130 of 132) of the patients received doses within the range of 45-50 Gy over 25 fractions. Mean clinical follow-up was 101 months, and mean radiologic follow-up (CT) was 8 years. Clinical complications occurred in 7% (nine of 134) of patients. There were two secondary malignancies, three visual complications, and two cases of auditory deterioration, and there were two posttreatment cerebrovascular accidents that may or may not have been related to radiation therapy. Only two of the 82 follow up CT scans available revealed evidence of ischemic changes within the radiation fields. PMID- 8497643 TI - Color Doppler flow imaging in central retinal vein occlusion: a new diagnostic technique? AB - Central retinal vein occlusion (CRVO) is a common cause of sudden visual loss and can occur at any age. Accurate diagnosis is essential, as differentiation of ischemic and nonischemic forms of the disease has prognostic importance. The introduction of color Doppler flow ultrasound has, for the first time, allowed visualization of the retrobulbar vessels; the central retinal artery and vein are easily identifiable. The authors conducted a prospective, blinded trial and compared images and waveforms from 20 patients with CRVO with those from 20 age matched healthy volunteers. No difference in velocity indexes from the central retinal artery was detected between the patients' affected and unaffected eyes or between the affected eyes and control eyes. A marked reduction in venous velocity was recorded in the central retinal vein in the affected eyes when compared with that of the unaffected patient and control eyes. There was no difference in venous flow between the unaffected patient and control eyes. These initial results suggest that color Doppler flow imaging may have a role in the diagnosis of CRVO. Color Doppler flow imaging is non-invasive, is easy to perform, is well tolerated by patients, and allows temporal assessment. PMID- 8497644 TI - Fine-needle biopsy of cervical lymph nodes in patients with thyroid cancer: a prospective comparison of cytopathologic and tissue marker analysis. AB - Tissue levels of thyroglobulin (Tg) or calcitonin were compared with specimens from neck lymph node biopsy in patients with suspected recurrent differentiated (papillary or follicular) or medullary thyroid cancer. Thirty-six neck lymph node biopsies were performed in 29 patients. Tissue Tg levels were obtained from 31 specimens from patients with differentiated thyroid cancers, and tissue calcitonin levels were obtained from five specimens from patients with medullary cancer. Thirteen nodes were diagnosed as negative for cancer at surgery (n = 3) or follow-up sonography (n = 10). Malignant disease was confirmed at surgery in 23 of the 36 lymph nodes. Cytopathologic examination had a sensitivity of 91% and a specificity of 100%. Tissue Tg levels ranged from 0 to 3.5 ng/mL (mean, 1.5 ng/mL; median, 1.2 ng/mL) in 12 of the 13 benign lymph nodes and from 21 to 247,500 ng/mL (mean, 30,600 ng/mL; median, 2,330 ng/mL) in the 23 malignant nodes. Tissue calcitonin levels were elevated (range, 850-703,125 pg/mL; mean, 184,762 pg/mL; median, 17,538 pg/mL) in four malignant nodes and were normal (3.0 pg/mL) in one benign node. Diagnostic sensitivity of tissue markers was 91%. Specificity was 91%. The combined diagnostic sensitivity and specificity of tissue marker analysis and cytopathologic examination was 100%. PMID- 8497645 TI - Placement of a ferromagnetic intracerebral aneurysm clip in a magnetic field with a fatal outcome. AB - Magnetic resonance (MR) imaging may be contraindicated in patients with biomedical devices, among the most dangerous of which are intracranial aneurysm clips, owing to the possibility of torque and dislodgement. A case is presented in which a patient with a reportedly nonferromagnetic clip was placed in a magnetic field. The patient developed an acute intracerebral hemorrhage in the MR unit, with a fatal outcome. Imaging studies strongly suggested a torqued clip as the cause. Autopsy revealed a torn middle cerebral artery from clip movement, and the clip was identified as a ferromagnetic type. This is the first reported case, to the authors' knowledge, of a fatal outcome due to an intracranial aneurysm clip placed in a magnetic field. PMID- 8497646 TI - Pituitary microadenomas: early enhancement with dynamic CT--implications of arterial blood supply and potential importance. AB - In a search for early contrast medium enhancement, which can indicate the presence of direct arterial supply, a retrospective review of dynamic computed tomographic (CT) scans was performed in 260 patients with a pituitary microadenoma smaller than 10 mm in diameter. Fifty patients underwent examination with dynamic CT for nonendocrinologic disease as a control group to establish the normal pattern of pituitary gland enhancement. One hundred seventy microadenomas (65.4%) displayed the usual dynamic CT pattern (ie, they did not show early enhancement before that of the portal system of the pituitary gland: those pituitary microadenomas appeared less enhanced than the normal pituitary gland during the entire examination). On the other hand, in 90 microadenomas (34.6%), early partial or complete enhancement was seen within the microadenoma before the normal portal enhancement of the gland. Therefore, analysis with dynamic CT yields two groups of pituitary microadenomas separable on the basis of blood supply: those with portal blood supply only and those with partial or predominantly direct arterial blood supply; in theory, the second group avoids hypothalamic control. PMID- 8497647 TI - Neuromagnetic mapping of brain function. AB - Magnetic source imaging, a technique that combines magnetoencephalography (MEG) and magnetic resonance (MR) imaging, was used to localize the somatosensory and auditory cortex in seven healthy subjects. Functional neuromagnetic data were obtained with a 37-channel biomagnetometer. Structural MR imaging data were obtained with a 1.5-T superconducting imager. Coordinates used in defining MEG and MR imaging space were reconciled to produce magnetic source images that displayed the putative locations of somatosensory and auditory activity in relation to brain anatomy. Sources of somatosensory activity were typically localized to the postcentral gyrus; sources of auditory activity were localized to the superior temporal plane. Extension of these results to patients with tumors (or other disorders) that distort normal brain anatomy has the potential to make noninvasive magnetic source imaging examinations clinically useful in guiding neurosurgical interventional procedures. PMID- 8497648 TI - Tangential fluoroscopic guidance of the anesthetizing needle during transthoracic needle lung biopsy: a randomized controlled clinical trial. AB - The effectiveness of tangential fluoroscopic guidance of the anesthetizing needle to avoid transgression of the pleura and therefore lower pneumothorax and chest tube insertion rates after transthoracic needle lung biopsy (TNB) was investigated. Tangential guidance was used in 41 patients (group A) and was not used in 51 (group B). The pneumothorax rate was 39% (16 of 41) for group A and 31% (16 of 51) for group B. The chest tube insertion rate was 12% (five of 41) for group A and 4% (two of 51) for group B. None of the differences in rates were significant. Use of this technique does not lower pneumothorax or chest tube insertion rates in patients undergoing TNB. PMID- 8497649 TI - Discrimination of the intravascular lumen and dissections in a single 30-MHz US image: use of "confounding" blood backscatter to advantage. AB - At 30-MHz intravascular ultrasound, the high-intensity backscatter of blood confounds discrimination of the intravascular lumen from the arterial wall. The authors developed and used a subtraction method to visualize the lumen and dissections through cancellation of backscatter from static areas. In two patients who underwent angioplasty of the superficial femoral artery, the residual hyperechoic pattern created by moving blood allowed good differentiation between the wall and lumen or dissections. PMID- 8497650 TI - CT gantry tilt: utility in transthoracic fine-needle aspiration biopsy. Work in progress. AB - The authors used a gantry tilt of 20 degrees in five patients to allow fine needle aspiration biopsy of peripheral pulmonary lesions that were difficult to approach with a vertical alignment because of overlying ribs. This method allowed a direct approach to the lesion in all five cases, with the entire needle path visible in the scanning plane, avoidance of vital structures, and traversal of a minimal amount of normal lung parenchyma. PMID- 8497651 TI - Staging prostate cancer with MR imaging. PMID- 8497652 TI - Cine scintigraphy of gastrointestinal bleeding. PMID- 8497653 TI - Cytologic examination and tumor antigen assay for classification of ovarian cysts. PMID- 8497654 TI - Controversy regarding screening mammography under age 50: to screen or not to screen. PMID- 8497655 TI - The effects of antiarrhythmic drugs on the signal-averaged electrocardiogram in patients with malignant ventricular arrhythmias. AB - Late potentials arise from areas of slowly depolarizing myocardium and may represent the substrate for sustained VTs. Because they may be recorded from the body surface using signal-averaging techniques, they represent a noninvasive marker for potential malignant ventricular arrhythmias. The effects of antiarrhythmic drugs on the SAECG and late potentials are reviewed in this article. Unfortunately, there is no SAECG parameter (either total QRS, late potential, or frequency content) that appears to be useful in predicting drug efficacy. However, there are type-specific changes in global ventricular activation that can be quantified by the SAECG. These changes may be useful in categorizing the effects of new type I antiarrhythmic drugs. The effects of antiarrhythmic drugs on tachycardia cycle length are complex and probably represent combined effects of the drug on conduction and refractoriness. Such changes cannot be reliably categorized by the SAECG. Medical therapy of sustained VTs cannot be guided by the SAECG. PMID- 8497656 TI - Beat-to-beat high-resolution electrocardiogram: technical and clinical aspects. PMID- 8497657 TI - Electrophysiologic basis of ventricular late potentials. PMID- 8497658 TI - Overview of frequency-time (spectro-temporal) analysis of signal-averaged electrocardiograms. PMID- 8497659 TI - Retardation and arrest of progression or regression of coronary artery disease: a review. PMID- 8497660 TI - [Molecular mechanism of protein translocation across endoplasmic reticulum membrane]. PMID- 8497661 TI - [Molecular mechanisms for vesicular transport and sorting in secretory pathway]. PMID- 8497662 TI - [Molecular mechanisms of GTP-driven vesicular transport]. PMID- 8497663 TI - [Molecular mechanism of protein secretion in Escherichia coli]. PMID- 8497664 TI - [DNA intercalation; x-ray crystallographic studies]. PMID- 8497665 TI - [Functional structure of chromatin in gene expression and regulation--nucleosome positioning]. PMID- 8497666 TI - [An introduction to cell cycle]. PMID- 8497667 TI - [CSF and Mos]. PMID- 8497668 TI - Effects of a procedural/belief intervention on breast self-examination performance. AB - The purpose of this study was to test the effect of a theoretically based nurse delivered intervention on BSE behavior. A 2 x 2 prospective, randomized, factorial design yielded four groups: control, belief intervention, procedural intervention, and procedural/belief intervention. A total of 301 women were randomly selected from a target population. One year following intervention, significant differences in self-reported proficiency, observer-rated proficiency, and sensitivity (lump detection) were found between the Procedural and Control Group and the Procedural/Belief and Control Group. Significant increases were found on observer-rated proficiency and sensitivity for the Procedural/Belief Group when compared to the Belief Group. In addition, a significant increase was found in the Procedural/Belief Group on nodule detection, when compared to the Procedural Group alone. PMID- 8497669 TI - Effect of warm and cold applications on the resolution of i.v. infiltrations. AB - Differences in pain intensity, surface area measurements of induration and erythema, and interstitial fluid volume when warm versus cold applications were randomly made to an intentional intravenous infiltrate of 5 mL of a designated solution were examined. Three solutions were used: 1/2 saline (154 mOsm), normal saline (308 mOsm), and 3% saline (1027 mOsm). Differences in volume were determined by magnetic resonance imaging (MRI) at three intervals postinfiltration. The sample was 18 healthy adults between 20 and 45 years. There was no difference in remaining infiltrate when 1/2 saline or normal saline were used, but a significant (p < .001) difference was found with 3% saline. For all solutions there was a significant (p < .001) difference in the volume of infiltrate remaining when warmth was applied and this effect held across MRI readings and solutions. Pain intensity did not differ by treatment but a significant (p < .005) difference was found by solution, with 3% saline producing the greatest difference. Erythema was absent with all solutions. Surface induration was affected by solution and decreased over time (p = .001). There was no effect of warmth or cold on surface area induration. PMID- 8497670 TI - Themes of loss and dying in caring for a family member with AIDS. AB - The study purpose was to provide an in-depth description of experiences associated with loss and dying among AIDS family caregivers. Grounded theory provided the methodological framework for data collection and analysis. In-depth interviews were conducted with 53 family caregivers of persons with AIDS and included individuals from family of origin and family of choice. Living with loss and dying was identified as a major substantive category and was further explicated in two subcategories: facing loss and transformed time. Common strategies of caregivers included taking one day at a time, living fully in the present, and actualizing future dreams. PMID- 8497671 TI - Variables related to caregiver behaviors with cognitively impaired elders in institutional settings. AB - The purpose of this study was to identify variables that might influence the behaviors of institutional caregivers when they interact with institutionalized, cognitively impaired elders. Independent variables included type of care situation, type of institution and nursing unit, and selected characteristics of both the caregiver and elder. The care situation was found to have a significant effect on caregiver behaviors. Caregiver characteristics of knowledge of dementia, experience in working with demented elders, and total years of education were significantly related to several caregiver behaviors. Elder characteristics of years of education, number of diagnoses, time on the nursing unit, age, self-care ability, and extent of dementia were related to several caregiver behaviors. Caregiver behaviors did not vary by the elder's gender. PMID- 8497672 TI - Insufficient milk supply among black and white breast-feeding mothers. AB - The purpose of this study was to investigate whether ethnicity is associated with insufficient milk supply (IMS) among breast-feeding mothers. A major reason reported by mothers for early termination or introduction of formula and/or solids is insufficient milk. A retrospective survey was conducted among 42 black and 148 white breast-feeding mothers participating in the WIC program in a midwestern state. The results suggested that: (1) the incidence of IMS was similar for black and white mothers; (2) controlling for education, black mothers initiated breast-feeding later and stopped sooner; IMS mothers fed less frequently and for shorter periods; and (3) controlling for education, there were no ethnic differences in the determinants or indicators of IMS. PMID- 8497673 TI - Theory unmasked: the uses and guises of theory in qualitative research. AB - The role of theory in qualitative research is variable and not always well understood. In this article, the uses and varied manifestations of theory at the substantive and paradigmatic levels of research, and as they pertain to different qualitative approaches, are described. Specific consideration is given to the varied sources, centrality, temporal placement, and functions of theory in qualitative research. PMID- 8497674 TI - The qualitative research audit trail: a complex collection of documentation. AB - A qualitative study typically involves a large volume of researcher-generated data, including notes about the context of the study, methodological decisions, data analysis procedures, and self-awareness of the researcher. Such data are important in many aspects of the study, particularly in the development of an audit trail to substantiate trustworthiness. Unfortunately, there is little information available to assist researchers in generating the needed documentation. In this article, we discuss the types of data that contribute to credible investigations. Strategies for maintaining effective records in qualitative studies are included, along with examples from our own research. PMID- 8497675 TI - Focus on psychometrics. Development and administration of a survey instrument for cross-cultural research. AB - The purpose of this article is to provide a brief review of guidelines for development of culturally appropriate measures of phenomena. The principles are illustrated by citing an example of their use in developing a survey instrument to be used with a rural Mexican American and Euro American population. Discussion focuses on practical issues of implementing the approaches suggested in the literature and adds to the literature about issues in formatting and administration of survey instruments used in cross-cultural research. PMID- 8497676 TI - Re: Assessment of convergent and discriminant validity. PMID- 8497677 TI - Re: Politics, policy, and research. PMID- 8497678 TI - A prospective audit of the value of fibre optic bronchoscopy in adults admitted with community acquired pneumonia. AB - We audited our practice of bronchoscoping patients admitted with community acquired pneumonia to detect latent underlying abnormalities. Fifty-five bronchoscopies were performed immediately after clinical recovery in 64 sequential patients without obvious underlying carcinoma. Five (9.1%) showed abnormalities (four carcinomas and one mild tracheal stenosis). The detection rate of abnormalities and the number of unnecessary bronchoscopies would be improved if only those patients aged 50 years or over who were current or ex smokers were bronchoscoped. In this group 13.9% (5/36) had an underlying abnormality. The cost implications of such a policy of early bronchoscopy are discussed and compared with traditional follow-up. PMID- 8497679 TI - Inhaled ipratropium bromide and terbutaline in asthmatic children. AB - Inhaled bronchodilator therapy in young asthmatic children reduces symptoms and improves lung function. After a single dose of therapy, however, lung function may still be abnormal, as evidenced by an elevated function residual capacity (FRC). The aims of this study were to assess if a second dose of bronchodilator therapy resulted in further improvement in lung function and to determine whether additional therapy was more effective if given as a second dose of a beta adrenergic agonist or if instead an anticholinergic was used. Twenty-one asthmatics (median age 7.5 years) received in random order on two separate occasions, 1 week apart, either two doses of terbutaline (500 micrograms) or terbutaline plus ipratropium bromide (20 micrograms). FRC and peak expiratory flow rate (PEFR) were measured immediately prior to and then 20 min after each dose of bronchodilator therapy. In the group, overall FRC and PEFR improved after the first and second dose of bronchodilator, regardless of regime used, the response to the second dose, however, was smaller than the first dose. There was no significant difference overall between the two regimes in baseline FRC or PEFR, or FRC and PEFR measured after each dose of bronchodilator. Eight children failed to show a significant change in FRC following two doses of terbutaline, but seven of these eight did have a significant change in FRC in response to the combination of terbutaline and ipratropium bromide. We conclude that a second dose of bronchodilator therapy does further improve lung function. Our results suggest the more efficacious regime consists of a combination of single doses of ipratropium bromide and terbutaline. PMID- 8497680 TI - Measuring lung volumes in advanced asbestosis: comparability of plethysmographic and radiographic versus helium rebreathing and single breath methods. AB - Total lung capacity was measured in 16 workers with pulmonary asbestosis using four standard methods: body plethysmography, radiographic lung area, helium dilution by multiple breath and by single breath (alveolar volume). All men had irregular opacities of ILO profusion category 2/1 or greater and four had pleural plaques in addition. The radiographic and plethysmographic methods produced virtually identical mean values for TLC of 7.52 l and 7.64 l and for RV of 4.06 l and 4.32 l and all values were larger than those by helium dilution. The closed circuit helium dilution method systematically underestimated TLC with a mean of 5.89 l as did single breath helium dilution with a mean of 6.39 l. These men had a larger mean RV/TLC, measuring 56.9% by body plethysmography and 54.6% by X-ray area than by the rebreathing dilutional method which was 43.8%. Air trapping within a normal TLC which characterizes asbestosis is revealed by radiographic and plethysmographic methods but concealed by gas dilution methods. Use of the latter is at least partly responsible for the impression that asbestosis is a 'restrictive disease'. PMID- 8497681 TI - Duration of preventive effect of inhaled salbutamol on early airway response to allergen in asthmatic subjects. AB - Salbutamol is known to effectively prevent early asthmatic response (EAR) after specific bronchial provocation test (sBPT) in asthmatic subjects, but the time course of this protection is not known. In this study the effects of 200 micrograms salbutamol inhaled 2 h before sBPT were compared with 200 micrograms salbutamol inhaled 10 min before sBPT in eight asthmatic subjects sensitized to Phleum pratensis (PP) or Dermatophagoides pteronyssinus (DP). All subjects showed an EAR (% decrease in FEV1 from baseline value: 30.4 +/- 11%) in a preliminary sBPT performed with cumulated doses of extracts of PP or DP titrated in biological units (BU). Each subject performed, on two different days, in a random, double-blind, cross-over study, two puffs of placebo 2 h before sBPT and two puffs of salbutamol 10 min before sBPT (treatment A) or two puffs of salbutamol 2 h before sBPT and two puffs of placebo 10 min before sBPT (treatment B). Baseline FEV1 were similar in both tests. In treatment B, 10 min, 1 h and 2 h after salbutamol inhalation, FEV1 increased significantly with respect to placebo inhalation in treatment A. Ten minutes after salbutamol inhalation in treatment A, FEV1 became similar to that obtained 2 h after salbutamol inhalation and 10 min after placebo in treatment B. Allergen inhalation induced an EAR in only one out of eight subjects after treatment A, and five of the eight subjects after treatment B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497682 TI - Results of tuberculosis contact tracing: Blackburn 1982-90. AB - Between 1982 and 1990, 649 index cases of tuberculosis were seen of which 429 (66.1%) were of Indian Subcontinent (ISC) ethnic origin: 7017 close contacts of these cases were screened, 50 cases of tuberculosis were detected (7.7% of notifications) and 372 children given chemoprophylaxis. All cases of tuberculosis detected in the white ethnic group were contacts of smear-positive pulmonary disease, six (46%) found at initial screening, five (38%) at 1 year and one (8%) at 2 year follow-up. Of 37 cases detected in the ISC ethnic group, only 14 (38%) were contacts of smear-positive disease, 17 (46%) being contacts of other respiratory disease, and six (16%) contacts of non-respiratory disease. Eighteen (49%) of ISC cases detected were at initial screening, with six (16%), eight (22%) and three (8%), respectively, at 6 month, 1 year and 2 year follow-up. The results support the revised Joint Tuberculosis Committee advice on contact tracing, with differential contact programmes depending on type of disease and ethnic group of index cases. PMID- 8497683 TI - Effect of a leukotriene antagonist, ONO-1078, on bronchial hyperresponsiveness in patients with asthma. AB - To evaluate the involvement of sulphidopeptide leukotrienes on bronchial hyperresponsiveness in asthma, we examined the effects of a specific orally active leukotriene antagonist (ONO-1078) on bronchial responsiveness to methacholine in stable asthmatic subjects by a double-blinded, randomized, two phase crossover study. Eleven asthmatic subjects received ONO-1078 (225 mg twice a day) or placebo. After 1 week administration of ONO-1078 or placebo, the subjects underwent methacholine challenge test. Test drug administrations were then discontinued for 1 week, and the subjects were then crossed over to the alternative treatment regimen. After 1 week of the alternate regimen, the subjects underwent a second methacholine challenge. Mean baseline values of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) and geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) were equal between the first and the second methacholine test. The geometric mean value of PC20-FEV1 after the administration of ONO-1078 was 0.48 (geometric SEM, 1.48) mg ml-1, which was significantly (P < 0.01) greater than the value after the placebo administration (0.30 geometric SEM, 1.41 mg ml-1), but the baseline values of FVC and FEV1 were not altered by ONO-1078. We conclude that sulphidopeptide leukotrienes are significantly involved in the development of bronchial hyperresponsiveness in asthma but the degree of the involvement may be small. PMID- 8497684 TI - The relationship between severe asthma and social class. AB - Asthma is one of the few diseases which has been reported to be common in the higher social classes. In order to assess the relationship between severe asthma and social class we analysed a national study of disabled adults undertaken by the Office of Population Censuses and Surveys (OPCS). The study estimated that there were 5.8 million people over 16 years with some degree of disability living in private households in England and Wales. Thirteen percent of disabilities were due to respiratory disease: 6% chronic bronchitis and emphysema, 3% asthma and allergy, and 4% other respiratory diseases. Among 10,000 individuals interviewed, 338 disabled adults reported asthma as a contributing cause of their disability. Of 291 cases with social class recorded, 41 (14%) were in social classes 1 and 2, 128 (44%) in social class 3, and 122 (42%) in social classes 4 and 5. An estimate of the relationship between social class and adult asthma in the general population was derived by calculating a morbidity ratio for the different social classes. The morbidity ratio for all social classes combined equals 100: for social classes 1 and 2 it was 63 (95% confidence intervals 48, 91); 93 (95% confidence intervals 77, 109) for social class 3; and 131 (95% confidence intervals 108, 153) for social classes 4 and 5. Adults in social classes 4 and 5 were approximately twice as likely to have severe asthma as those in social classes 1 and 2. This could be as a result of differences in the prevalence or treatment of asthma among the social classes. PMID- 8497685 TI - Intestinal obstruction complicating malignant mesothelioma of the pleura. PMID- 8497686 TI - Pneumocystis carinii pneumonia associated with weekly methotrexate: cumulative dose of methotrexate and low CD4 cell count may predict this complication. PMID- 8497687 TI - Home nebulizer treatment and current smokers. PMID- 8497688 TI - Arteriolar pulmonary resistance and ventilatory equivalent for oxygen. PMID- 8497689 TI - Chemoprophylaxis for tuberculosis. PMID- 8497690 TI - Pulmonary involvement in lymphoma. PMID- 8497691 TI - Haemodynamics and gas exchange in liver cirrhosis: the effect of orally administered almitrine bismesylate. AB - The present study was conducted to analyse the effect on haemodynamics and to evaluate the role of hypoxic pulmonary vasoconstriction (HPV) in cirrhotic patients with hypoxaemia using almitrine bismesylate, an agent which increases the response of HPV. Six male patients, mean age of 51 years, with hepatic cirrhosis and associated hypoxaemia were studied. All patients had normal lung and cardiac function tests. When the patients were clinically stable, right heart and radial artery catheterization were performed. Data from the pulmonary artery catheter and blood gases were obtained before and after 4 days of oral almitrine bismesylate. The results indicated that these cirrhotics were in a mild hyperdynamic circulatory state. The cardiac output (CO), cardiac index (CI), oxygen delivery (DO2), and oxygen consumption (VO2) were elevated while the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were low. Almitrine significantly increased PVR (P < 0.05) and mean pulmonary artery pressure (mPAP) (P < 0.01). In addition, almitrine improved alveolar arterial oxygen content difference [D(A-a)O2] (P < 0.01) and shunt fraction (Qva/QT) (P < 0.01). The PaCO2 and PaO2 increased slightly but this was not statistically significant. In conclusion, in our group of patients with hepatic cirrhosis, four days of treatment with almitrine improved their gas exchange. The data suggest a weak HPV response in this group of cirrhotics; that response may be enhanced by almitrine. PMID- 8497692 TI - Salbutamol output from two jet nebulizers. AB - Nebulized bronchodilators are commonly used in the management of patients with airflow obstruction, although there is little information available on the bronchodilator output from the nebulizer unit. We have examined the fluid and salbutamol outputs of a single jet nebulizer from two commercial manufacturers at 1 min intervals up to 12 min. The drug and fluid output continued throughout the study period, with a greater fluid output leading to an increase in the concentration of salbutamol remaining within the nebulizer unit. This suggests that weight change is not a good indicator of drug output. Furthermore, there was a marked difference in peak salbutamol output between the two nebulizer units, being 2.9 mg (55%) with the Micro-Neb unit and 1.98 mg (38.7%) with the System 22 unit. PMID- 8497693 TI - Preoperative pulmonary function testing. PMID- 8497694 TI - Infection, asthma and bronchial hyperresponsiveness. PMID- 8497695 TI - Inhalational injuries produced by smoke and nitrogen dioxide. PMID- 8497696 TI - Respiratory tract epithelium and neoplasia. PMID- 8497697 TI - Labelling shift from acute bronchitis may be contributing to the recent rise in asthma mortality in the 5-34 age group. AB - To test the hypothesis that labelling shift from acute bronchitis to asthma may be contributing to the rise in deaths from asthma in the U.K., we studied mortality rates for males, females and both sexes combined for all ages and for the 5-34 age group, from published mortality tables from 1950 to 1985. The 5-34 age group mortality from asthma showed the 1960s peak and a more gradual increase from 1975. Mortality (all ages) from acute bronchitis showed a decline over the period, but in the 5-34 age group mortality was remarkably stable from 1950-1974 with a mean rate of 2.61 per million (95% confidence intervals, 2.44-2.78). From 1975 to 1985 the rate declined linearly to 0.75 per million. The number of acute bronchitis deaths 'saved' over this period was 366 compared to the number of excess asthma deaths during the same period (taking the 1974 rate as baseline) of 514. These findings lend support to the hypothesis that, in the 5-34 age group, labelling shift from acute bronchitis to asthma may be a contributing factor to the recent rise in asthma mortality. They also raise the question whether different factors contributing to the rise in asthma may have proportionately different weights of effect according to the age of the patients involved. PMID- 8497698 TI - Respiratory dysfunction following cardiopulmonary bypass: verification of a non invasive technique to measure shunt fraction. AB - Respiratory dysfunction is a well recognized complication of cardiopulmonary bypass. The size of the pulmonary shunt fraction is the best indicator of respiratory dysfunction but its measurement conventionally requires use of a pulmonary artery catheter to measure mixed venous oxygen content. We compared pulmonary shunt fraction, based on a non-invasive technique using a previously described mathematical model, with shunt fraction measured invasively using a pulmonary artery catheter in 22 patients undergoing elective coronary artery surgery. The mean shunt fraction measured by the invasive technique was 19.6 +/- 2.0 (18.8-20.4)% of cardiac output at 24 h (+/- 1 SD and 90% confidence intervals) and 20.9 +/- 2.9 (19.8-22.0)% of cardiac output at 44 h post-surgery. There was good agreement between the two methods of measurement. The mean difference was 0.21 percentage points with 95% confidence interval -0.01 to 0.43. The limits of agreement (-1.17 to 1.59) are small enough to be confident that the non-invasive method can be used to give the same result as that obtained using a pulmonary artery catheter. The values for shunt fractions obtained by the non invasive technique were 19.7 +/- 2.3 (18.8-20.6)% of cardiac output at 24 h and 20.7 +/- 2.5 (19.7-21.6)% of cardiac output at 44 h. The non-invasive measurement of the shunt fraction provided us with a simple, practical method for following a further ten patients over an extended period of time where prolonged catheterization is impractical. PMID- 8497699 TI - Nasal intermittent positive-pressure ventilation in weaning intubated patients with chronic respiratory disease from assisted intermittent, positive-pressure ventilation. AB - Nasal intermittent positive-pressure ventilation (NIPPV) has been used for domiciliary ventilatory support, and to avoid intubation for acute respiratory failure in patients with chronic airflow limitation (CAL). Its role in weaning patients from assisted ventilation in intensive care has not been defined. We have used NIPPV to wean 14 patients with respiratory disease who were referred either because of predicted difficulty in weaning or failure to wean using standard techniques. Twelve patients were ventilated for acute respiratory failure; eight patients had CAL and four had chest wall or neuromuscular disease. Two further patients with chest disease were difficult to wean following surgery. Weaning was successful in 13 patients. NIPPV corrected hypoxia, reduced hypercapnia and was well tolerated. Weaning from NIPPV was achieved in all patients with CAL, although three patients with chest wall disease later required domiciliary ventilatory support. All but one of the patients survived to leave hospital. NIPPV may have an important role in weaning from assisted ventilation, particularly in patients with underlying chronic respiratory disease. This preliminary report needs to be followed by a controlled study comparing NIPPV with established weaning methods. PMID- 8497700 TI - Family clusters of pulmonary tuberculosis in a suburban area of Japan. AB - A survey was conducted in a metropolitan suburb to examine family clusters of pulmonary tuberculosis patients and related factors. Firstly, a descriptive study was done based on the review of tuberculosis registration cards over a 11-yr period. Of 1106 cases, 109 (9.9%) were found to occur in households which had already had one or more pulmonary tuberculosis patient during the period. The most affected were four- and eight-member families with infants and adolescents accounting for most of the second or later patients. Secondly, a home visit survey was performed to investigate factors associated with family clusters of phthisis. Results showed that significant variables were the length of patient's delay (interval between perception of physical symptoms and visit to the physician), the number of rooms, and lack of self-motivation to seek treatment. Log-linear analyses revealed interaction among these variables. PMID- 8497701 TI - Comparison of methotrexate 30 mg per week with placebo in chronic steroid dependent asthma: a 12-week double-blind, cross-over study. AB - Methotrexate has been shown to have a steroid-sparing effect in chronic steroid dependent asthmatics at a dose of 15 mg week-1. The aim of this study was to investigate the steroid-sparing activity and adverse events profile of methotrexate 30 mg week-1 in severe steroid-dependent asthma. Eighteen patients who had required 10-50 mg week-1 prednisolone for at least 6 months were asked to participate in a randomized, double-blind, placebo-controlled cross-over study lasting 24 weeks. Daily diary cards of symptoms, peak expiratory flow rate and medication requirements were kept and the patients attended for a chest X-ray, spirometry, lung volumes and gas transfer at commencement and after each 12-week treatment period. Every 3 weeks, adverse events were noted and blood taken for full blood count, urea and electrolytes and liver function tests. Twelve patients completed the trial. Withdrawals were due to non-compliance in two patients, pneumonia in two patients, depression in one patient (on placebo) and severe nausea in one patient. Adverse events were common, probably as a consequence of the higher dosage. Prednisolone requirements were not significantly reduced on methotrexate. Lung function improved on methotrexate with a significant rise in maximal mid-expiratory flow rate and a trend towards improvement in FEV1. PMID- 8497702 TI - Respiratory function at follow-up after neonatal surfactant replacement therapy. AB - Respiratory function was assessed at a median of 7 months (range 6-12) in 17 preterm infants who, in the neonatal period, had been entered into a multi-centre randomized placebo-controlled trial of prophylactic surfactant replacement therapy. Seven infants (median gestational age 28 weeks) received surfactant and the remaining ten infants (median gestational age 27 weeks) placebo. Respiratory function was assessed by measuring functional residual capacity (FRC), thoracic gas volume (TGV) and airways resistance (RAW). Specific conductance (SGAW) was calculated from RAW and TGV. There was no significant difference in FRC or TGV between the two groups. RAW, however, was significantly lower in the surfactant (median 41, range 21-48 cmH2O l-1 s-1) compared to the placebo group (median 57, range 40-68 cmH2O l-1 s-1), P < 0.05 and SGAW significantly higher in the surfactant (median 0.136, range 0.063-0.289 l cmH2O-1 s-1) compared to the placebo group (median 0.081, range 0.062-0.134 l cmH2O-1 s-1), P < 0.05. These results suggest that surfactant replacement therapy improves lung function at follow-up. PMID- 8497703 TI - Laparoscopic cholecystectomy in patients with cystic fibrosis. PMID- 8497704 TI - Hazards of domiciliary oxygen therapy. PMID- 8497705 TI - Respiratory arrests in young asthmatics on salmeterol. PMID- 8497706 TI - Diffuse panbronchiolitis: efficacy of low-dose erythromycin. PMID- 8497707 TI - Thoracoscopy. PMID- 8497708 TI - Prescribed respiratory diseases in the 1990s. PMID- 8497709 TI - Anti-neutrophil cytoplasmic antibodies. PMID- 8497710 TI - Effects of corticosteroids on bone turnover. AB - The pathophysiology of corticosteroid-induced osteoporosis is complex, but centres around a primary inhibition of osteoblastic activity compounded by the effects of secondary hyperparathyroidism. The preservation of the microanatomy of bone in the early stages of the disease, coupled with strategies to prevent the emergence of secondary hyperparathyroidism, and the potential availability of osteoblastic stimulants offer the hope of minimizing this important side-effect of corticosteroid therapy. PMID- 8497711 TI - Asthma, growth and inhaled corticosteroids. AB - Linear growth can be divided into three phases: during infancy it is influenced mainly by nutrition; thereafter throughout childhood it comes under hormonal control; puberty constitutes the third phase. The pubertal growth spurt, which may account for up to 30 cm of linear growth, results from an increase in growth hormone pulse amplitude that is mediated by sex steroids. The rate of growth in childhood, onset of puberty and final height are determined by the impact of a range of environmental factors on genetic potential. These variables and the effect of asthma itself need to be taken into account when assessing the possible effect of inhaled corticosteroids on growth. Many asthmatic children have a slower growth rate than normal children, and a physiological delay in puberty which does not affect final adult height. Prolonged administration of oral corticosteroids retards growth. The mechanism is not fully understood, but may involve an indirect effect on growth hormone secretion following adrenal suppression. Short-term deceleration of growth has been demonstrated by knemometry in children taking inhaled corticosteroids, but there is no evidence of long-term growth suppression with conventional doses of inhaled corticosteroids. Growth should be monitored in children taking over 0.8 mg day-1 of inhaled corticosteroid, but the priority should be to treat the asthma adequately. PMID- 8497712 TI - Safety of high-dose inhaled corticosteroids. AB - Inhaled corticosteroids are being given to more patients, at increasing doses and for longer periods of time. This has led to renewed concern about side-effects, particularly when higher doses (> 1 mg day-1) are used. The side-effects of particular concern are adrenocortical suppression, bone resorption, decreased growth in children, skin thinning and cataract formation. Changes in adrenocortical function are seen in a small proportion of patients given doses of 1-2 mg day-1. Long-term studies of the effect of inhaled corticosteroids on bone density are not available. Cross-sectional studies of bone density have been performed, but confounding variables, such as previous courses of oral corticosteroids and poor matching of control groups, make the studies difficult to interpret. Short-term effects on markers of bone turnover have been demonstrated, but their relevance to the long-term risk of osteoporosis is unclear. Studies reporting an increased incidence of skin changes and cataract formation are difficult to interpret because of confounding variables and inadequate control groups. Further studies of the long-term side-effects of inhaled corticosteroids are now required to enable prescribers to judge better the relative benefits and risks of this important asthma therapy. PMID- 8497713 TI - Bone physiology and the osteoporotic process. AB - Bone continually undergoes modelling (during growth) or remodelling (during adult life), brought about by the co-ordinated action of osteoblasts and osteoclasts. Osteoblasts form new bone, whereas osteoclasts are responsible for bone resorption. Both types of cell are under hormonal regulation. Osteoporosis, a reduction in bone mass, predisposes to fracture. The most important cause of osteoporosis is oestrogen deficiency which results in increased bone turnover in which resorption exceeds formation. Corticosteroids can also induce osteoporosis in which trabecular bone is particularly affected. This mainly results from suppression of osteoblastic activity. PMID- 8497714 TI - Inhaled corticosteroids--effect on bone? AB - Asthmatic patients receiving long-term therapy with oral prednisolone have been found to have an increased incidence of vertebral fractures. Measurements of bone density have shown that diminished bone density is associated with administration of oral corticosteroids rather than with the disease. Inhaled corticosteroids have some systemic activity and although serum calcium and parathyroid hormone levels are unaffected by corticosteroids, inhaled corticosteroids at doses of more than 1.0 mg day-1 have measurable effects on bone metabolism in normal subjects. PMID- 8497715 TI - Methods of measurement of bone turnover and clinical evaluation of osteoporosis: relevance to asthma and corticosteroid therapy. AB - Bone turnover can be assessed by measurements of biochemical markers. Serum alkaline phosphatase and osteocalcin can be used as indices of bone formation, and hydroxyproline and pyridinium crosslinks in urine can be used to assess bone resorption. These markers are able to detect changes induced by high-dose corticosteroid therapy given by the oral or inhaled route. However, a clinical diagnosis of osteoporosis requires, in addition, the presence of at least one relatively atraumatic fracture. Fracture risk may be assessed by in vivo measurement of bone density, for which a number of new techniques, including single-photon absorptiometry, dual-photon absorptiometry, dual-energy X-ray absorptiometry, and quantitative computed tomography, have been developed and are now in clinical use. PMID- 8497716 TI - [The excimer laser and corneal refractive surgery]. PMID- 8497717 TI - [Roxithromycin versus doxycycline in the treatment of Chlamydia trachomatis cervicitis in asymptomatic women]. AB - We have performed an experimental open study, non randomized, in a population of women pertaining to a family planning center, and who have been diagnosed of Chlamydia trachomatis infection through EIA and DNA probe. 75 patients were included in the study, 50 of them received roxitromycine; 150 mg every 12 hours during 10 days, the other 25 being treated with doxycycline, 100 mg each 24 hours during 10 days. All women underwent a control after treatment using both techniques a month later, to asses the efficacy of the treatment. Mean age of women treated with roxitromycine was 28.6 years, and 30 years the ones treated with doxycycline. Efficacy in the eradication of Chlamydia trachomatis was 91.7% in the group treated with macrolide, and 92% in the group treated with doxycycline. Comparison through Chi-square did not yield statistical significance with a p < 0.05. Only a patient treated with doxycycline showed gastric intolerance. Roxitromycine shows an in vivo activity similar to doxycycline, and is an alternative to the use of doxycycline, being the first choice in those women in whom tetracycline are contraindicated. PMID- 8497718 TI - [Aztreonam as monotherapy in urinary tract infections with a systemic repercussion in patients with a relative contraindication for the use of aminoglycosides]. AB - A comparative study has been performed to evaluate the clinical efficacy and safety of aztreonam in the treatment of urinary tract infections with systemic affectation, in a group of patients who showed a relative contraindication to be treated with aminoglycosides. The group studied was formed by 30 patients (21 females and 9 males). Mean age of said group was 78 years and percentage of patients over 65 years was 93%. Moreover, 53.3% of patients showed nephropathy, 30% diabetes mellitus and 16.6% hearing disorders. Responsible germ of the infection was identified through blood and urine culture in 24 patients (80%) being the most frequent isolated E. Coli (60%). The cure rate was of 76.6% and improvement rate was 13.3%. Three deaths happened on the studied group (10%). In a patient superinfection due to Enterococcus was detected. There were no significative adverse effects (hypersensibility reactions, hematological disorders, nephrotoxicity or hepatotoxicity). Aztreonam could be an efficacious alternative in the treatment of urinary infection with systemic affectation, caused by gram-negative germs, showing low toxicity. PMID- 8497719 TI - [The clinical spectrum of patients with anticentromere antibodies]. AB - In order to define the clinical associations and diagnostic meaning of anticentromere antibodies in a random population of patients, clinical and serological findings were studied with the evolution of 16 patients selected only because of their positiveness to anticentromere antibodies, detected by indirect immunofluorescence on HEp-2 cells and confirmed in chromosome spreads of HMcB cells. The most frequent diagnosis was systemic sclerosis in 9 patients (56%) especially in its variety Limited Cutaneous Systemic Sclerosis/CREST (7 patients). The rest of the cases (44%) showed different diseases (3 isolated Raynaud's phenomena, 1 Sjogren's syndrome, 1 seronegative polyarthritis, 1 undifferentiated connective tissue disease and a probable sarcoidosis). Therefore, even tough the more frequent clinical entity associated to anticentromere antibodies was systemic sclerosis and especially its variety Limited Cutaneous Systemic Sclerosis/CREST its diagnostic specificity is relatively low. The most frequent clinical association in our group of patients with positive anticentromere antibodies has been Raynaud's phenomena, alone or associated to other processes, being found in all but one of the studied patients (94%). PMID- 8497720 TI - [Diffuse mediastinal lipomatosis and exogenous obesity]. AB - A case of diffuse mediastinal lipomatosis (ML) is described, associated to exogenous obesity, infrequent entity, which is comprehended within the causes which can cause mediastinal broadening. The clinical characteristics of our observation and the general aspects of interest are reviewed for this type of mediastinal affectation. PMID- 8497721 TI - [The first case of thalassemia intermedia in Spain due to the interaction of 3 alpha genes with beta-thalassemia minor]. AB - We have identified the case of a 9-months-old girl with heterozygotic thalassemia and triplication of alpha genes of globin (alpha alpha alpha 3.7). Molecular defect of thalassemia was a mutation without sense of 39 codon. Patient's phenotype was an intermediate thalassemia with moderate splenomegaly and marked unbalance on the globin chains. This is the first case of intermediate thalassemia, through this mechanism, described in Spain. PMID- 8497722 TI - [Visceral leishmaniasis located in the intestines in patients with human immunodeficiency virus infection: a report of 2 cases]. AB - We discuss two cases of visceral leishmaniasis (VL) with intestinal invasion in patients diagnosed of infection due to human immunodeficiency virus (HIV). The onset was as diarrheic manifestation associated to a constitutional syndrome, with no fever. One of the patients responded to treatment with antimonials, while the other died. References on this subject are scarce, being found on a literature search two similar cases as the ones described by us. We think that with every diarrheic process in HIV+ patients, VL diagnosis should be considered, and an intestinal biopsy should be performed. PMID- 8497723 TI - [An analysis of 100 consecutive tuberculosis cases in HIV-infected patients in a hospital in Cantabria]. AB - In our setting, patients infected by human immunodeficiency virus (HIV) show a high rate of tuberculosis infections which manifestations depend on the level of immunodeficiency reached. METHOD: Clinical, radiological and evolutive characteristics are discussed of 100 diagnosed tuberculosis in seropositive patients during a time span of 52 months, relating them to the number of CD4 detected. RESULTS: Tuberculosis pulmonary forms (65%) were more frequent than extra-pulmonary ones (35%) even in the advanced phases of the disease due to HIV, even tough the latter tend to cluster in patients with less than 200 CD1/mm. An unspecific febrile syndrome, normal results on simple radiological exploration and the difficulty to obtain diagnostic samples are facts which often delay the diagnosis. CONCLUSION: Even tough the extra-pulmonary forms are more frequent in the last stages of the disease due to HIV, in our setting there is still a high incidence of pulmonary forms in all stages. PMID- 8497724 TI - [New physiological and pharmacological aspects of the growth hormone (I). The effects in adults]. AB - Growth hormone (GH), a well-known anabolizing agent, not only plays a physiological role in childhood by promoting longitudinal growth, but also it remains to be secreted during adult life. Many aspects on physiological and pharmacological actions of this hormone in adulthood have been clarified in the last years. GH induces the biosynthesis of insulin-like growth factor I (IGF-I), a peptidic compound that acts as a mediator of indirect actions of GH. In GH deficient adults, exogenous GH administration produces a decrease in adipose mass which is accompanied by an increase in lean body mass, mainly due to an enlargement of muscle cell mass. Sodium and water retention has been also described. An augmentation in muscle strength, basal metabolic rate and nitrogen retention by action of GH are expressions of the potential anabolizing effects of this hormone in adult life. Glucose tolerance is decreased by GH, and this effect is accompanied by a decrease in peripheral utilization of glucose and an increase in insulin secretion. GH behaves as a lipolytic hormone and gives rise to an increase in resistance to the lipogenetic action of insulin. GH treatment increases plasma levels of bone Gla protein and other marker of osteoblastic activity, what suggests a physiological role of GH in bone turnover regulation. Many other organic functions are also affected by GH administration. PMID- 8497725 TI - [A woman of 25 with pleural effusion and neurological deterioration]. PMID- 8497726 TI - [Cutaneous myiasis in the shoulder after a stay in South America]. PMID- 8497727 TI - [Severe hypokalemia in delirium tremens]. PMID- 8497728 TI - [A myxoma in the posterior wall of the right atrium]. PMID- 8497729 TI - [Acute kidney failure due to rhabdomyolysis with normal blood calcium: a possible diagnostic marker of the presence of cocaine abuse]. PMID- 8497730 TI - [Pulmonary vasculitis in Behcet's disease]. PMID- 8497731 TI - [Acute kidney failure due to a nitrofurazone cream]. PMID- 8497732 TI - [The attitude of hospital nursing professionals toward HIV-positive patients]. PMID- 8497733 TI - [Hodgkin's disease and the human immunodeficiency virus: the need for an expansion of the AIDS definition]. PMID- 8497734 TI - [Massive pulmonary atelectasis as the first manifestation of a hypernephroma]. PMID- 8497735 TI - [Thrombocytopenia secondary to treatment with chlorpromazine]. PMID- 8497736 TI - [The clinico-mammographic follow-up of breast cancer after conservative treatment]. AB - Clinical and mammographic follow-up of 149 patients diagnosed of stage I and II breast neoplasm and treated with conservative surgery and irradiation between January 1986 and December 1988 was reviewed to determine clinical and radiographic recurrence pattern. Follow-up controls included a clinical examination and a mammogram at 6-9 months, a second at 10-16, a third at 17-22, a fourth at 23-24 and a mammogram yearly and a clinical examination every 6 months thereafter. To December 1991 18 patients recurred. 12 had a metastatic spread, 3 a unique local recurrence and 3 a local recurrence with a metastasis spread. Clinical recurrence was as a carcinomatous mastitis in three patients and a solid nodule in two. Radiologic recurrence was as an augmented skin thickness in three patients. Mammogram was not performed in one patient because an associated poor prognostic metastatic spread. Mammographic skin thickness secondary to irradiation appeared in 93% of the patients at 6-9 first control, 62% at second, 50% at third and 35% at fourth. The number of recurrences is scarce to achieve any clinical, pathological or treatment factor associated with greater risk of recurrence. We suggest that first mammogram should be delayed after 12 months of treatment because we would not obtain any relevant clinical information before, once observed skin thickness persistence at 6 months and most frequent recurrence radiologic pattern. PMID- 8497737 TI - [Tuberculosis and human immunodeficiency virus infection. A prospective study of 215 patients]. AB - We analyze the cases of 215 adult patients affected from tuberculosis (TB) and infection due to human immunodeficiency virus (HIV) in the study period from December 6th, 1986 to January 31st of 1992. Disease affected specially the group of drug addict patients (DAP) with a 74.88%, followed by paid plasma donors (PPD) from our city with a 12.09%. Sexual transmission was the route of contamination with the HIV in 16 cases. In five cases atypical mycobacteria were detected. First-line anti-tuberculostatics drugs activity against Mycobacterium tuberculosis was excellent. A total of 17 cases with toxicity to any of these drugs were described. TB was located in the lung in 108 cases (50.23%), in 74 cases out of the lung (34.41%) and in 33 cases there was intrapulmonary as well as extrapulmonary affectation (15.34%). TB was diagnosed at the same time that a disease which met AIDS criteria in 13.49% of cases, TB was diagnosed first in 32.55% of cases, and AIDS was diagnosed before TB in only 7.91% of cases. Fever was the predominant symptom (88.84%), together with toxic status at admittance (80.47%) and deteriorated immune situation with lymphocytes count decrease (mean 1240/mm) and CD4 (mean value 134.5/mm) together with a mean raised IgA (492.85 mg/dl). Thorax radiography was normal in 34.88%. In 33 of these patients TB was localized in the lung, in 27.91% primary radiologic types were observed while in 31.16% reactivation types. In 51 cases (23.72%) tuberculosis was detected in patients (DAP) who were forwarded from the penitentiary system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497738 TI - [The functional sequelae of Mycoplasma pneumoniae pneumonia]. AB - To check the possible existence of long-term pulmonary functional sequelae in patients with pneumonia due to Mycoplasma pneumoniae, 17 patients who showed evident spirometric disorders during the recovery from the acute phase of a pneumonia due to Mycoplasma pneumoniae were studied. In the acute phase of the disease, 7 patients showed a ventilatory restriction, 6 of them had an obstructive pattern while in four patients a mixed pattern was observed. After a latency period, which mean length was 39 months, it was seen that there was a return to normal values of the spirometric conventional parameters initially altered in all cases. However 5 patients (33%) who did not smoke, showed a significant decrease on the maximum flows at low volume. These results suggest that in a high percentage of adult patients, as has been previously described in children, pneumonia due to M. pneumoniae could leave as a sequelae the persistent affectation of small airway. PMID- 8497739 TI - [Mediastinal fibrosis]. AB - Even tough the ultimate etiologic and pathogenic mechanisms of mediastinal fibrosis are not quite established, several causes have been mentioned as the more frequent inducers, such as histoplasmosis, tuberculosis and other granulomatous diseases. Generally the diagnosis is suggested by a hilar or mediastinal mass, which is seen in thorax radiography, because 40% of patients are asymptomatic. Exeresis of fibrotic Magma is difficult because usually there is no separation with trachea neither with superior cava vein. That is why many times we have to restricted ourselves to the surgical approach on the complications. The present work discusses three new cases of mediastinal fibrosis. PMID- 8497740 TI - [Hemoptysis caused by a bronchial artery aneurysm. Apropos a case]. AB - We discuss the case of a right bronchial artery aneurysm in its intrapulmonary trajectory which manifested itself by repeated mild hemoptysis. Diagnosis was made through selective angiography of bronchial artery and during the same procedure it was treated through transcatheter embolization. We have reviewed the literature and found 17 cases of bronchial artery aneurysms with intrapulmonary or mediastinal localization. PMID- 8497741 TI - [New physiological and pharmacological aspects of the growth hormone (II). Therapeutic applications in adults]. AB - Normal human ageing is associated with changes in body composition which include a decrease in muscle mass and strength, bone mass loss and increase in adipose mass. A physiological decrease in growth hormone (GH) and IGF-I secretion accompanies these changes. Many of the physiological changes that accompany normal human ageing are very similar to those found in GH deficient patients. Nevertheless, responsiveness to exogenous administered GH persists with advancing age. GH administration to elderly individuals has produced an decrease in fat mass and an increase in lean body mass, being this finding consistent with the hypothesis that GH deficiency could be a contributing cause to senescent changes in some elderly individuals. GH treatment has also been used with encouraging results in adult subjects with isolated or combined GH deficiency. On the other hand, several clinical studies have recently shown the efficiently of GH treatment on diverse pathological processes such as severe catabolic states (surgery, sepsis, trauma, buns), osteoporosis, diabetic ulcers and obesity. The most frequent side effects are sodium and water retention, impairment in glucose tolerance and carpal tunnel syndrome, although in general the treatment has been well tolerated. The clear definition of the therapeutical applications of GH in the adult warrants further clinical investigation. PMID- 8497742 TI - [Chronic arthropathy of the knee: a magnetic resonance study]. PMID- 8497743 TI - [The quality perceived by the consumers of the outpatient consultation services of a university hospital]. AB - With the objective to know the perceived quality of the assistance by the customers of the outpatient facilities in a teaching hospital, the information gathered in 1,970 self-administered, volunteer, anonymous questionnaires was analyzed, being obtained from the 4,756 consultations done in the outpatients department during a one week period. Different aspects of the physician's visit are discussed, together with the attention received from the paramedic personnel and other viewpoints pertaining to the organization and conditions of the waiting area. There is a high level of satisfaction among the users of the outpatients department, more pronounced in the "medical" area, in relation with the physician's consultation as well as with the attention from paramedics or in the adherence to appointments. The results suggest that in those physicians' offices where the relationship of the patient with the unit is less frequent, users show more criticism in comparison with those offices where almost all patients consult because of chronic ailments. We underline the importance of this type of perceived quality studies within the quality control policies, as a complement of the analysis of technical quality. PMID- 8497744 TI - [Visceral leishmaniasis associated with transient paraproteinemia]. PMID- 8497745 TI - [Acute cholestatic hepatitis due to roxithromycin]. PMID- 8497746 TI - [Comments on the yellow nail syndrome]. PMID- 8497747 TI - [Pseudomonas paucimobilis infections. An analysis of 2 cases]. PMID- 8497748 TI - [Hepatic nodular regenerative hyperplasia: apropos 2 cases]. PMID- 8497749 TI - [Lead poisoning and hobbies]. PMID- 8497750 TI - [Pyridostigmine bromide: a new cause of a false positive in the biochemical diagnosis of pheochromocytoma]. PMID- 8497751 TI - [Scurvy in adults: a rare entity]. PMID- 8497752 TI - [Myasthenia induced by penicillamine: does an interaction with tricyclic antidepressants exist?]. PMID- 8497753 TI - [Diagnosis and treatment of photodermatoses]. PMID- 8497754 TI - [Is age a limiting factor in carotid artery surgery?]. PMID- 8497755 TI - [Psoriatic rheumatism]. PMID- 8497756 TI - [Non-specific bronchial hyperreactivity: epidemiological aspects and clinical significance]. PMID- 8497757 TI - [Hepatic angiosarcoma in a patient with autoimmune hepatitis]. PMID- 8497758 TI - [Multicenter study of the efficacy and tolerance of naftazone (Mediaven 10 mg). Comparison of 2 dosage schemes]. PMID- 8497759 TI - [Post-traumatic calcified hematoma of the spleen]. PMID- 8497760 TI - [Medicine and physicians in the work of George Simenon]. PMID- 8497761 TI - [What is your diagnosis? Pyoderma gangrenosum in ulcerative colitis]. PMID- 8497762 TI - [Hyposensitization treatment of allergic diseases]. AB - Hyposensitization or allergenic immunotherapy has been used extensively for 80 years as a specific treatment of IgE-mediated allergic diseases. Highly effective is venom immunotherapy for patients with systemic reactions after hymenoptera stings and positive diagnostic tests for venom-specific IgE. The clinical efficacy of immunotherapy in hay fever has also been convincingly documented. 20 to 30% of patients with allergic rhinitis pollen develop asthma at a later stage of the disease. Some studies have shown a significant efficacy of immunotherapy in reducing the further development of rhinitis into asthma. The clinical efficacy of immunotherapy in allergic asthma to house-dust mites, animal danders or moulds has been questioned; however, a number of controlled studies published during the last decade shows a clear tendency towards a beneficial effect, especially in children. Recent data show a reduction in mediator release induced by immunotherapy and an inhibition of the late-phase reaction following skin and bronchial challenge tests. Immunotherapy and pharmacotherapy should be integrated components of the treatment strategy of allergic diseases in order to gain the optimal result for the allergic patient. PMID- 8497763 TI - [Practice of hyposensitization in allergic diseases]. AB - Hyposensitization (desensitization, immunotherapy) is--next to avoidance of allergens--the only causal treatment of IgE-mediated allergic diseases. In a number of well-controlled studies, immunotherapy has shown a clinical efficacy in allergic rhinitis, mainly hay fever, and in allergic asthma. Here, immunotherapy is primarily useful in children and young adults. Immunotherapy is highly effective in hymenoptera-venom allergy. The quality of the extracts in terms of potency and composition is essential both to the diagnosis of relevant allergens and to an optimal result of immunotherapy. The hyposensitization extracts used in Switzerland are listed in the 'Spezialitatenliste des Bundesamtes fur Sozialversicherung' and have, therefore, to be payed for by the health insurance. Since the early seventies so-called semi-depot extracts are used in practice; here, the allergens are adsorbed to aluminium hydroxide and thus liberated in a delayed way. For a few years a short-term therapy, using so-called depot allergoids, is possible. A hyposensitization should be initiated only after a through evaluation and a careful allergological examination. With regard to pollen allergies one has to take into consideration especially the presence of the leading pollens, the cross-reactivity and the patient's account of his symptoms. The practice of hyposensitization is discussed extensively. The information of the patient regarding efficacy, length of treatment and risk of side effects is of great importance. PMID- 8497764 TI - [Diagnostic clues in the clinical diagnosis of joint diseases]. AB - Most rheumatic joint diseases can be diagnosed by a careful clinical history and examination of the patient. The differential diagnosis considers typical age at onset, sex, pattern of joint involvement and the occurrence of extra-articular manifestations. In addition to laboratory tests and joint fluid examination, conventional radiographic investigations are very important for both the assessment of the diagnosis and the evaluation of the disease process in patients with rheumatic joint disorders. PMID- 8497765 TI - [Thoracoscopic surgery: current indications]. AB - Recent advances in the technologies for minimal invasive surgery have expanded the indications for thoracoscopic surgery. The thoracoscopic approach is for various operations, including pleurectomy, decortication, pulmonary wedge resection, pericardial window, the approach of first choice. Other operations such as resection of tumors in the mediastinum or thoracic wall, lobectomies or others, can often be performed by thoracoscopy. Indications and technical details are described. PMID- 8497766 TI - [Cell-specific therapy of HIV infection]. PMID- 8497767 TI - The cumulative effect of cadmium sulfide. PMID- 8497768 TI - CDT Today: new standards for practical examinations-complete dentures. PMID- 8497769 TI - Ceramic shade selection: by whom, where, and under what circumstances. PMID- 8497770 TI - [Dangerous arrhythmias]. AB - The usual frequent tachyarrhythmias well known to the specialists in internal medicine, such as ventricular tachycardia and ventricular fibrillation, are not discussed in this publication; nor are the bradycardias connected with the sick sinus syndrome or with atrioventricular block of higher degrees (with one exception). In the first section a stratification of the risk after myocardial infarction is presented including the therapeutic implications. Severely reduced left ventricular function is of most negative prognostic value. After the poor results of the CAST study, which revealed a threefold greater mortality of patients with myocardial infarction and severely impaired left ventricular function under treatment with some antiarrhythmic agents of class I (Vaughan Williams), compared to patients on placebo, cardiologists have resorted to beta blocking agents again or, in patients with severely reduced left ventricular function, to amiodarone (Cordarone), based on preliminary results of current amiodarone studies. For selected patients, implantable cardioverter-defibrillator (ICD) devices seem to have a promising future. In the second part some rare and persistent arrhythmias are mentioned that may induce heart failure in an otherwise healthy heart, such as ectopic atrial tachycardia, atrioventricular junctional tachycardia with RP > PR, His bundle tachycardia and idiopathic ventricular tachycardia (this arising only in infants). In the third section some infrequent forms of tachycardia are discussed that may be sporadically encountered in a medical office. Ventricular tachycardia of the type "torsades de pointes" is associated with on a prolonged QT or QTU time in the ECG and is mainly due to drugs (especially antiarrhythmic agents). The therapy consists in withdrawal of the drug and may include magnesium intravenously and even a temporary pacemaker. The tachycardias associated to the Wolff-Parkinson-White syndrome have gained more practical importance since it has become possible to localize the accessory pathway involved by mapping with subsequent interruption by surgery or ablation. In atrial fibrillation with an ECG pattern of delta waves at the beginning of QRS complexes, digitalis and verapamil are contraindicated since they may induce ventricular fibrillation. The Mobitz type is one, and the most rare, form of the three atrioventricular blocks of second degree. It is almost always combined with an infra-His-bundle conduction disturbance in the conducted beats, and is an immediate precursor of complete atrioventricular block. Patients with the Mobitz block usually need a pacemaker. Finally, two case reports are presented to show that superficial and incorrect diagnosis of an arrhythmia is followed by incorrect and dangerous therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8497771 TI - [Hypertensive crisis]. AB - Hypertensive crisis is a life-threatening situation caused by acute elevation of blood pressure. The rise in blood pressure is very rapid and thus overwhelms protective adaptive mechanisms in the arterioles which occur under physiological conditions. Endothelial damage results. Focal vessel wall ischemia, inappropriate constriction and dilatation of arterioles, and increase in vascular permeability develop and cause functional disturbances of the heart, central nervous system or kidneys. Without immediate treatment, irreversible organ damage results due to ischemia and hemorrhage. The goal of therapy is to lower blood pressure by 25% within one hour. Blood pressure should be maintained at this level for 24 hours. Thereafter, blood pressure may be reduced by an additional 25% or to 180/100 mm Hg. Initial reduction in blood pressure by 55% may provoke irreversible end organ ischemia and infarction although blood pressure still may be well above the normal range. Most frequently, hypertensive crisis is treated with sodium nitroprusside as it allows controlled reduction in blood pressure due to its very rapid onset but short duration of action. Cyanide toxicity may develop in patients treated with high doses of sodium nitroprusside or with renal or kidney failure. Other agents used may have disadvantages such as unpredictable antihypertensive effects (calcium channel blockers, angiotensin converting enzyme inhibitor [ACEI]), tachycardia (calcium channel blockers, phentolamine, dihydralazine) or reduced renal blood flow (betablocker, ACEI). PMID- 8497772 TI - [Hypotensive crisis]. AB - The physiology of arterial blood pressure regulation is briefly reviewed and the differential diagnosis of arterial hypotension discussed. The shock syndrome consists of four different forms: cardiogenic, obstructive, hypovolemic, and distributive shock. The etiology of anaphylaxis is mentioned and its therapy outlined. Patients with Addison's disease or severe hypothyroidism are hypovolemic, but peripheral resistance is also altered. Therapy consists of hormone replacement. The cytokines play a major role in the pathogenesis of septic shock. At present there are no therapeutic tools available to modulate their detrimental effects clinically. PMID- 8497773 TI - [Emergencies in angiology]. AB - Acute arterial occlusions of the extremities present with the classical five P's: pain, pallor, pulselessness, paresthesia, paresis. Loss of sensitivity and motility are symptoms of the most severe grade of ischemia. The occlusions are due to embolism in about 70% of subjects and to local thrombosis in 30%. These patients have to be treated immediately with heparin. In the mildest forms, deobliteration is desirable, but in the more severe cases rapid restoration of flow not only saves limbs but also life. Deobliteration may be performed surgically or by means of catheters (local thrombolysis or thrombus aspiration) if available. Deep vein thrombosis, the other kind of emergency situation, requires immediate anticoagulation as soon as pulmonary embolism is suspected. It should be initiated by heparin and followed by oral anticoagulation. In patients presenting without pulmonary embolism but a swollen leg, ruptured Baker cysts or muscle hematomas should be ruled out before anticoagulation is started. Systemic thrombolysis or surgical thrombectomy is reserved for young patients with acute isolated thromboses. Thrombectomy must also be kept in reserve for the most severe form of deep venous thromboses, the phlegmasia cerulea dolens. In thrombophlebitis, no anticoagulation is indicated except in bedridden patients. The others must remain mobile and may be treated by systemic and local antiinflammatory drugs, incision of thrombosed varices, and bandages. PMID- 8497774 TI - [The alcoholic emergency]. AB - Gastric lavage, intestinal charcoal decontamination and specific drug antagonism, therapeutic measures widely applied in other intoxications, are of no clear benefit or unavailable in patients with alcohol intoxication. The gastric first pass-effect is important in modifying the kinetics of alcohol, and clinically relevant drug-alcohol interactions occur in situations of both acute and chronic alcohol abuse. Alcohol-induced hypoglycemia and ketoacidosis should be considered in every severely ill alcoholic patient. The recognition of alcoholism is important and rewarding, since therapeutic action by the practicing physician can be of significant help. PMID- 8497775 TI - [Drug emergencies]. AB - Opiate intoxication accounts for the majority of emergencies related to substance abuse. The concomitant intravenous and intramuscular administration of the specific narcotic antagonist naloxone is warranted in such cases. Further threatening complications of opiate abuse include rhabdomyolysis, noncardiogenic pulmonary edema, and both peripheral and central nervous lesions. Opiate abuse is often associated with benzodiazepine abuse. Hence, intravenous administration of the antagonist flumazenil is indicated in patients with suspected acute opiate intoxication resistant to naloxone. Cocaine abuse is not frequent in this country but is usually very severe and clinically heterogeneous. The clinical pattern of cocaine intoxication is initially due to excitatory and later to depressant effects on central nervous, circulatory and respiratory systems. The treatment of acute cocaine intoxication is symptomatic. The internal concealment of cocaine and other drugs in packets (body-packing) may lead to bowel obstruction or to acute intoxication following leaking or breaking of packets. PMID- 8497776 TI - [Acute poisoning--a brief review]. AB - Poisonings are frequently encountered in hospital emergency departments. Approximately 80% of poisonings occur by ingestion of toxic substances. The basic approach to the poisoned patient includes initial stabilization to correct immediate life-threatening problems, treatment to reduce absorption, measures to improve elimination of the toxin and the use of specific antidotes. Traditional gastric lavage is indicated today in severely intoxicated patients if they present within the first few hours of ingestion. Administration of activated charcoal is recommended in most cases of poisoning. It should be administered early, in an adequate dose and repeatedly if necessary. PMID- 8497777 TI - [The wrong mushroom. Diagnosis and therapy of mushroom poisoning, especially of Amanita phalloides poisoning]. AB - By far the most frequent deadly intoxication with mushrooms is caused by Amanita phalloides. The diagnosis is based upon the long latency phase, the typical clinical picture of which includes four periods (the asymptomatic latent phase, the gastroenteritis phase, the oligosymptomatic interval and the hepatorenal phase), analysis of the mushrooms by the expert and the sensitive radioimmunoassay for amanitin in blood, urine or gastric content. The therapy includes (1) stabilisation of the patient with the correction of hypoglycemia and electrolyte imbalance, substitution with coagulation factors (FFP) and red cells and the treatment of septic complications, (2) decontamination, which consists of gastric lavage, the administration of activated charcoal and laxatives as well as the forced diuresis, and (3) therapy with high doses of penicillin or ceftazidime and of silibinine. The pathophysiological mechanisms are discussed. The other important types of mushroom intoxications are summarized in Table 1. PMID- 8497778 TI - [Malaria: the most important emergency in subjects returning from the tropics]. AB - Malaria is the most important emergency in people returning from tropical countries. Falciparum malaria may lead to coma and death within a few hours. The symptoms are generally not specific. A history of travelling in tropical countries is the most important factor in diagnosis. In the case of fever after a journey in the tropics, malaria must always be considered in the first place. Laboratory diagnosis is established by finding of plasmodia in blood smears. Vivax, ovale and quartan malaria is treated by chloroquine. Falciparum malaria is usually treated by mefloquine, Fansimef, quinine or quinidine. PMID- 8497779 TI - [Re: Etter CG, Wedgwood J, Schaad UB: Aseptic meningitis in pediatrics (Schweiz Med Wochenschr 1991; 121:1120-1126)]. PMID- 8497780 TI - [Endosonography in oncology of the upper gastrointestinal tract]. AB - Based on our own experience and on data from the literature, we report on the indications for and efficiency of endoscopic ultrasound (EUS) in the oncology of the upper gastrointestinal tract. At the present time the following conclusions can be drawn: Intramural tumors can be clearly visualized and differentiated from extragastric conditions by EUS. Pancreatic tumors smaller than 2 cm can be delineated exactly by EUS and the sensitivity of EUS in demonstrating pancreatic tumors is 90%, a fact which is especially helpful in the early diagnosis of endocrine tumors. Since the endosonographic aspect does not allow us to separate unequivocally benign from malignant alterations, a clear distinction between inflammatory (pseudo) tumors and neoplastic pancreatic lesions based on EUS findings alone is not possible. The main indication for EUS is in regional TN staging. The pT-stage of esophageal cancers can be determined correctly in 84% (73-92), of gastric carcinomas in 80% (69-92), of pancreatic cancers in 90% (88 92) and of the distal common bile duct and of papilla of Vater in 85% (83-89) of cases. EUS is superior to computed tomography, especially in early tumor stages. The correct EUS-staging of proximal bile duct tumors and of gallbladder cancer is far more difficult, especially when the latter is filled with stones. Local lymph node metastases are visualized by EUS in about 70-90% of cases. EUS is also valuable in evaluation of the anastomosis after operative resection of esophageal or gastric carcinoma, as well as in the follow-up of patients with gastric non Hodgkin lymphomas during radiochemotherapy. PMID- 8497781 TI - [Efficacy of adenosine triphosphate in terminating supraventricular tachycardia]. AB - The efficacy of adenosine triphosphate (ATP) was tested in 23 patients suffering from supraventricular tachycardia; 10 patients had orthodromic circus movement tachycardia and 13 typical av nodal reentrant tachycardia. At a mean dose of 0.18 mg/kg all tachycardias were halted in less than 1 minute due to transient acute av nodal block followed by return to normal av conduction within 8 seconds. All patients had transient minor side effects. One elderly subject had a short episode of atrial fibrillation after the acute av block. In conclusion, ATP is useful and safe for rapid termination of supraventricular tachycardias incorporating the av node in their circuit. PMID- 8497782 TI - [Bullet embolism. Case report and literature review]. AB - Migratory intravascular bullets may produce confusing clinical pictures in patients with gunshot wounds. We report on a patient in whom the missile entered the right chest at the fourth intercostal space in the anterior axillary line. The bullet was finally found in the abdominal aorta. The penetration site remained unclear but was probably the heart. After repair of the chest wall the bullet was successfully removed from the aortic bifurcation. PMID- 8497783 TI - [Low-dose laser therapy: critical analysis of clinical effect]. AB - Low dose laser therapy (LDLT) has been available for the treatment of various diseases for almost two decades. The aim of therapy is usually to reduce pain. The literature offers a plethora of reports, some negative and some positive. This review discusses the relatively few placebo-controlled, double-blind trials on the subject, in an attempt to provide an evaluation of the clinical effectiveness of LDLT. The majority of these studies suggest that LDLT is not clinically effective. There is no particular disease or symptom which seems to respond to LDLT. The same can be said of the type of laser light or its intensity. Based on this collective data, LDLT does not seem to be a scientifically proven therapy. PMID- 8497784 TI - [Annual meetings of the Swiss Societies of Infectology, Hematology, Pharmacology and Toxicology, and Endocrinology. Lausanne, 13-15 May 1993. Abstracts]. PMID- 8497785 TI - [Annual meeting of the Swiss Society of Medical Radiology. Fribourg, 14-15 May 1993. Abstracts]. PMID- 8497786 TI - [Initial experience in the use of 4F-dilatation catheters]. PMID- 8497787 TI - [Intestinal leiomyoblastoma--benign or malignant? The unusual case of a benign leiomyoblastoma with a triple location and a protracted malignant deterioration]. PMID- 8497788 TI - [An unusual diagnostic path in the case of an invagination]. PMID- 8497789 TI - [EKG changes during enteroclysis]. PMID- 8497790 TI - [Diagnosis of an intramural colonic lipoma using computed tomography]. PMID- 8497791 TI - [Follow up of liver metastases using computed tomography in colorectal cancer treated with interferon-alpha and 5-fluorouracil]. PMID- 8497792 TI - A selective history of groin herniorrhaphy in the 20th century. AB - Of the histories of the many operations available in a general surgeon's technical armamentarium, that of groin herniorrhaphy has been written about repeatedly. Many of these reports focus on developments prior to the twentieth century. This article, instead, details selective evolutionary changes relative to groin hernia surgery during the last nine decades. Among the surgeons discussed are Battle, Ferguson, La Roque, Cheatle, Gallie, Henry, Tanner, McVay, Shouldice, and Lichtenstein. PMID- 8497793 TI - Demographic, classificatory, and socioeconomic aspects of hernia repair in the United States. AB - Although demographic and socioeconomic data regarding the natural history of hernia disease are difficult to find, studies from the National Center for Health Statistics show that approximately 700,000 groin herniorrhaphies are completed annually in the United States. More than 60% of these operations are performed on an outpatient basis. Classification schemes relative to hernia repair serve as an important communication tool when retrieving and reporting operative results in a more comprehensive, reliable, and meaningful fashion. Part of the growing movement toward ambulatory surgery includes the construction of office-based operating suites by general surgeons. Because of the increasing number of hernioplasties completed in the outpatient setting, the use of a laparoscopic approach for hernia repair does not appear to provide any cost-saving benefits over existing conventional techniques. PMID- 8497794 TI - Anesthesia for hernia surgery. AB - The knowledge and skills of the anesthesiologist enable him or her to evaluate and prepare a patient and then to choose and administer anesthesia in a way that provides safety and good operating conditions. Current anesthesia practice tends toward less extensive routine laboratory screening and less aggressive NPO policies. Advances in pharmacology allow more rapid recovery with fewer unpleasant drug side effects. These factors contribute to making hernia surgery, particularly in the outpatient setting, an increasingly safe and benign experience. PMID- 8497795 TI - Inguinal and umbilical hernia repair in infants and children. AB - Inguinal hernia repair is the most common operation performed in infants and children. In this article, the embryology, clinical presentation, and treatment of congenital inguinal hernias and umbilical hernias in children are reviewed. Specific attention is directed to such topics as the incarcerated hernia, hernias in girls, hernia repair in premature infants, and anesthetic considerations. PMID- 8497796 TI - The Shouldice repair. AB - A series of more than 200,000 groin hernias repaired at Shouldice Hospital since 1945 has had an overall recurrence rate of 1%. Thorough and extensive dissection is essential. The technique employed since 1953 for inguinal hernia repair is described in detail. Adjunctive measures for the repair of femoral hernias and for the most difficult recurrent hernias also are discussed. PMID- 8497797 TI - The Cooper ligament repair. AB - Although a Cooper ligament repair is a more extensive operation than most hernia repairs, it can be done safely with minimal morbidity and a very low recurrence rate. A generous relaxing incision and careful technique around the femoral vessels are required. Many surgeons would choose a Cooper ligament repair for direct, large indirect, and femoral hernias only. I have used it for all groin hernias in adults, primary or recurrent, regardless of the presenting defect. I believe it is the best hernia repair done today. PMID- 8497798 TI - Iliopubic tract repair of inguinal and femoral hernia. The posterior (preperitoneal) approach. AB - There are two arms of inguinal hernia treatment herein presented--the approach and the repair. Whereas the posterior approach is not new, the repairs are unique, and details given are precise and must be followed carefully to obtain proven excellent long-term results. A classification of hernia types is outlined. PMID- 8497799 TI - The mesh-plug hernioplasty. AB - The evolution of tension-free hernioplasty techniques; culminating in the mesh plug repair, is presented. Experience with 1563 cases is described. Recurrences have been virtually eliminated. The factors of no tissue tension and decreased dissection are believed to be the two most important reasons why there is greater patient comfort, rapid rehabilitation, lowered cost, and diminished complications with the mesh-plug technique. The mesh-plug hernioplasty is recommended for the treatment of all groin hernias. PMID- 8497800 TI - Laparoscopic inguinal herniorrhaphy. Techniques and controversies. AB - Because of the remarkable success of laparoscopic cholecystectomy, numerous investigators have attempted to duplicate this success with laparoscopic herniorrhaphy. This article presents a different view of the preperitoneal anatomy, reviews the rationale behind the various laparoscopic approaches, and presents, in detail, the laparoscopic preperitoneal repair with mesh, including complications and early recurrences. An attempt is made to put the new laparoscopic procedures into perspective with regard to economic issues and safety. PMID- 8497801 TI - The cause, prevention, and treatment of recurrent groin hernia. AB - At present, groin hernia repair is associated with a 10% recurrence rate. Despite innumerable modifications of the Bassini technique, this depressing figure remains essentially unimproved. This article documents the two major reasons for failure and presents techniques that are simple, can be performed under local anesthesia in an outpatient setting, allow patients to return home within hours of their surgery, encourage rapid return to unrestricted activity, and are associated with a recurrence rate approaching 0%. PMID- 8497802 TI - Properitoneal prosthetic placement through the groin. The anterior (Mahorner Goss, Rives-Stoppa) approach. AB - The operative technique presented here, placement of polypropylene mesh in the properitoneal (deep) position through an inguinal approach, has yielded very satisfactory results with few recurrences and with postoperative morbidity rates comparable to those of standard techniques that do not involve prosthetic material. The main advantage of this method over other operations that utilize prosthetic material lies in the combination of the greater flexibility in the choice of operative technique afforded by the inguinal approach and the potential benefit of low recurrence rates after properitoneal placement of the mesh. There is an urgent need for a controlled randomized trial addressing the potential benefit (or lack thereof) of hernia repairs with prosthetic material in general, as well as the issue of optimal placement of the prosthesis. PMID- 8497803 TI - Incisional hernia. AB - Incisional hernias are a relatively common occurrence after abdominal operations, having been reported to occur in 2% to 11% of all patients undergoing such procedures. Although many hernias become manifest early, others may not be noted until many years after the index procedure. Predisposing factors for incisional hernia have been well described, and several of these can be altered by the surgeon, including the technique employed for repair. For many years, the repair of incisional hernia was associated with a high recurrence rate. In more recent years, the introduction of synthetic prosthetic materials has provided the opportunity to perform a tension-free repair, thereby reducing the rate of recurrence. PMID- 8497804 TI - Testicular atrophy and chronic residual neuralgia as risks of inguinal hernioplasty. AB - Testicular atrophy can be prevented by limiting dissection trauma to the spermatic cord, specifically, leaving the distal part of the indirect inguinal hernia sacs in situ; never dissecting beyond the pubic tubercle; and using the properitoneal space when it is advisable, as in recurrent hernias, to avoid dissection of the spermatic cord altogether. Chronic residual neuralgia may be debilitating and difficult to manage. The involved nerve may be identified by local anesthetic nerve blocks. Neurectomy of the ilioinguinal, iliohypogastric, and genitofemoral nerves may cure the neuralgia. PMID- 8497805 TI - Medical/legal aspects of hernia surgery. Personal risk management. AB - Professional liability is an unavoidable part of every physician's work; and sound practice management is the bedrock of protection against litigation. This article gives an overall assessment of the medical/legal problem, some commonly used legal terms and concepts, and a personal risk management code that has served the author well for more than 30 years. PMID- 8497806 TI - Cytoplasmic structure in organotypic cultures of rat hippocampus prepared by rapid freezing and freeze-substitution fixation. AB - We have compared rapid freezing followed by freeze-substitution fixation with conventional aldehyde fixation as preparative methods for the electron microscopic study of organotypic cultures of neonatal rat hippocampus. Rapid freezing by contact with a copper block chilled by liquid helium was accomplished without mechanical distortion of superficial structures, and preserved structure to a depth of at least 20 microns without visible ice crystals. Freeze substitution fixation in acetone/osmium tetroxide, followed by en bloc staining with tannic acid and uranyl acetate, provided satisfactory staining of cytoplasm and organelles. While both preparative techniques yielded generally satisfactory results, rapid freezing provided much better preservation of astrocytic lysosomal inclusions, and afforded new views of intermediate filament substructure. Rapid freezing and freeze-substitution fixation seemed especially well suited to the preservation of short filamentous proteins, such as those forming the membrane cytoskeleton of dendritic spines or those associated with synaptic vesicles. The combination of rapid freezing methods and organotypic culture provides an opportunity to examine cytoplasmic structure in tissue from deep regions of the brain which had previously been inaccessible to rapid freezing techniques. PMID- 8497807 TI - In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate. AB - There is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital-anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate-putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate-putamen area by more than 20-fold. In cortical areas, amphetamine's effect was less profound: An increase of 400-500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation. PMID- 8497808 TI - Repeated administration of Sigma ligands alters the population activity of rat midbrain dopaminergic neurons. AB - Acute and repeated administration of antipsychotic drugs produce distinctive profiles of electrophysiological effects on the population activity of midbrain dopaminergic (DA) neurons which correlate with their clinical effects. Sigma receptors have been hypothesized to be involved in psychosis and in the efficacy of antipsychotic drugs, but little is known about the effects of repeated treatment with sigma ligands on the activity of midbrain DA neuronal populations. In the present study, the cells-per-track cell-sampling method was used to evaluate the effects of 3 sigma ligands on the numbers of spontaneously active A9 and A10 DA neurons in chloral hydrate-anesthetized rats. One-hour pretreatment with either (+)-pentazocine (10 mg/kg, i.p.), DTG (2 mg/kg, i.p.), or JO 1784 (1 or 10 mg/kg, s.c.) did not alter the number of spontaneously active DA neurons encountered per electrode track. Repeated treatment (21 daily injections) with (+)-pentazocine (1 or 10 mg/kg) or DTG (0.2 or 2 mg/kg) increased the number of A10 DA cells per track; JO 1784 (10 mg/kg but not 1 mg/kg) moderately decreased the number of active A9 DA cells and increased the firing rate of A10 DA neurons. The effect of JO 1784 on A9 DA neurons was not due to depolarization inactivation. The effects of all 3 sigma ligands differ from those of antipsychotic drugs, all of which inactivate A10 DA neurons after repeated treatment. Clinical studies are necessary to determine if selective sigma ligands will provide a novel alternative to DA antagonists in the treatment of psychosis. PMID- 8497809 TI - In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring. AB - Chronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a regional increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open-field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine. PMID- 8497810 TI - Selective induction of Fos and FRA immunoreactivity within the mesolimbic and mesostriatal dopamine terminal fields. AB - The influence of the mesencephalic dopaminergic projections on the neurons within the basal forebrain and prefrontal cortex is not well understood although it has been intensely investigated. The purpose of this study was to evaluate the expression of Fos-like and FRA-like (Fos Related Antigens) immunoreactivity (IR) as a qualitative and quantitative marker of neuronal activity within the mesolimbic and mesostriatal dopamine terminal fields. Following the administration of apomorphine (5.0 mg/kg S.C.), a rapid increase in FRA-IR, accompanied by Fos-IR, was observed within the striatum in a patchy distribution. Apomorphine also induced the expression of FRA-IR within the nucleus accumbens, cortex, septum, and the islands of Calleja complex. This broad pattern of activation contrasts with the limited expression of Fos-IR and FRA-IR within the dorsolateral striatum, dorsomedial shell of the nucleus accumbens, and cingulate cortex following haloperidol administration (2.0 mg/kg, S.C.). Finally, it was observed that nuclei expressed Fos-IR rapidly and transiently within the striatum following haloperidol, whereas the number of FRA-IR nuclei remained elevated but changed in distribution and intensity over time. In conclusion, different regions within the dopamine terminal fields express varying concentrations of Fos-IR and FRA-IR after stimulation or blockade of dopamine receptors. These data indicate that Fos, as well as selective FRAs, can be used to delineate populations of neurons with altered metabolic activity resulting from the administration of dopaminergic agents. Furthermore, the data support the concept of segregated mesostriatal and mesolimbic projections, in particular the division of the nucleus accumbens into the shell and core compartments. PMID- 8497811 TI - CNS signal transduction in the pathophysiology and pharmacotherapy of affective disorders and schizophrenia. AB - Until recently, research on the neurochemical basis of affective disorders (AD) and schizophrenia (SCZ) focused on detecting postulated disturbances in presynaptic neurotransmitter release and metabolism, or postsynaptic receptor function. New insights into the molecular mechanisms involved in the propagation of neurotransmitter signals across biological membranes and in the regulation of neuronal responses have allowed the development of novel hypotheses, which may explain the altered postsynaptic neuroreceptor responsivity thought to be integral to the pathophysiology of these disorders. In this review we evaluate evidence from both basic science and clinical research implicating disturbances in postreceptor signal transduction in the pathophysiology and pharmacotherapy of AD and SCZ. Specific findings regarding potential postreceptor sites of pathophysiology are highlighted in each of these disorders, together with the growing body of data on the possible postreceptor loci of psychotropic drug action, especially lithium and antidepressants. PMID- 8497812 TI - Tuberculosis and HIV: blind man's buff. PMID- 8497813 TI - Diuretics and asthma. PMID- 8497814 TI - Asthma guidelines: who is guiding whom and where to? PMID- 8497815 TI - Tuberculosis and HIV: estimates of the overlap in England and Wales. AB - BACKGROUND: A study was designed to determine the extent of the interaction between tuberculosis and human immunodeficiency virus infection in England and Wales. METHODS: Data were obtained from the United Kingdom national AIDS surveillance and the Medical Research Council tuberculosis notification surveys in England and Wales (1983 and 1988). The proportion of patients reported with AIDS known to have had tuberculosis and the proportion of patients notified with tuberculosis known to have HIV infection were estimated. RESULTS: Of the 4360 patients with AIDS reported by 30 June 1991, 200 (4.6%) were in patients reported to have had tuberculosis. Only one of the 3002 patients (0.03%) reported in the 1983 survey of tuberculosis notifications in England and Wales was known to be infected with HIV compared with nine of 2163 patients (0.42%) in the 1988 survey. CONCLUSION: Although the reported number of cases of HIV infection with tuberculosis in this country is increasing it remains small. Complete reporting of cases of AIDS and notification of cases of tuberculosis are essential to enable the two infections to be monitored as the HIV epidemic develops. Special studies, such as those reported here, will need to be undertaken regularly to assess the future extent of the interaction. PMID- 8497816 TI - Changing patterns of respiratory disease in HIV positive patients in a referral centre in the United Kingdom between 1986-7 and 1990-1. AB - BACKGROUND: Respiratory illness is a significant contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). It has been suggested that Pneumocystis carinii pneumonia is no longer the most frequent cause of respiratory disease in this group because of widespread use of prophylaxis and anti-retroviral drugs. METHODS: A retrospective comparison of the diagnoses in HIV 1 antibody positive patients with respiratory illness admitted to a major UK centre in 1986-7 and 1990-1 was carried out to identify changes in patterns of respiratory disease. RESULTS: In the 1986-7 period there were 73 patients, of whom none received zidovudine or prophylaxis for pneumocystis pneumonia while in the 1990-1 period there were 122 patients. One hundred and ninety patients (98%) were male homosexuals. Pneumocystis pneumonia remained the commonest respiratory disease, comprising 68% of all diagnoses in the 1986-7 period and 48% in the 1990 1 period. Bacterial infections (bronchitis and pneumonia) were seen more commonly in the 1990-1 period (23%) than in the 1986-7 period (14%), as was pulmonary Kaposi's sarcoma (12% in 1990-1 and 4% in 1986-7). Mycobacterial infection remained uncommon (4% in 1986-7 and 6.5% in 1990-1). CONCLUSION: Despite widespread use of zidovudine and prophylaxis, pneumocystis pneumonia remains the commonest respiratory disease in homosexual men. PMID- 8497817 TI - The effect of inhaled frusemide on airway sensitivity to inhaled 4.5% sodium chloride aerosol in asthmatic subjects. AB - BACKGROUND: Frusemide inhaled by asthmatic subjects before a variety of indirect bronchial challenges inhibits the airway response to these challenges. Since inhalation of hyperosmolar saline is an indirect bronchial challenge, the effect of inhaled frusemide and its vehicle on airway sensitivity to a 4.5% sodium chloride (NaCl) aerosol challenge was investigated. METHODS: Eleven asthmatic subjects (five females, six males) who had a 20% fall in forced expiratory volume in one second after 4.5% NaCl challenge were enrolled in this double blind controlled crossover trial. Sensitivity was measured as the dose of aerosol required to provoke a 20% fall in FEV1. Frusemide (33.2 mg) or its vehicle was delivered through a Fisoneb ultrasonic nebuliser and inhaled 10 minutes before challenge with 4.5% NaCl. A Mistogen ultrasonic nebuliser was used to generate the 4.5% NaCl aerosol and FEV1 was measured before and one minute after each challenge period of 0.5, one, two, four, eight, eight and eight minutes. The doubling dose difference for PD20 was calculated. RESULTS: Frusemide or vehicle had no effect on baseline lung function. The geometric mean PD20 after vehicle was 1.3 ml with a 95% confidence interval of 0.7-2.3 and after frusemide was 8.2 ml with a 95% confidence interval of 4.7-14.1. This represented a 2.6 doubling dose increase in PD20 after frusemide inhalation. In five of the 11 subjects an increase from baseline FEV1 occurred after exposure to 4.5% NaCl challenge in the presence of frusemide. This transient bronchodilatation may be caused by the release of prostaglandin E2. CONCLUSION: Inhalation of frusemide is very effective in delaying airway narrowing induced by an aerosol of 4.5% NaCl in asthmatic subjects. PMID- 8497818 TI - Respiratory symptoms questionnaire for asthma epidemiology: validity and reproducibility. AB - BACKGROUND: There is a need for a new respiratory symptoms questionnaire for use in epidemiological research in asthma. METHOD: A questionnaire was designed following a pilot study in 78 subjects. It contains nine questions on symptoms such as wheeze and difficulty with breathing in defined circumstances such as exercise and sleep. It was completed by 211 adults and validated by comparison with a self reported history of asthma and with bronchial hyperresponsiveness to histamine. Its short term reproducibility was measured by three repeat administrations over two weeks. RESULTS: Subjects with asthma (n = 33), particularly those having had an asthma attack in the last year (n = 23), were more likely to report any symptom and to report a greater number of symptoms than those without asthma. The same relationship was found for bronchial hyperresponsiveness and symptoms. Either two or more, or three or more, symptoms appeared to be good indices of self reported asthma and bronchial hyperresponsiveness, or both, with a high sensitivity (65-91%) and specificity (85-96%). Reproducibility was good, with few subjects changing the number of symptoms reported by more than one symptom and none by more than four symptoms. The results compared favourably with those from questions on phlegm production from the MRC questionnaire and were better than those reported for the MRC wheeze questions. CONCLUSIONS: The questionnaire will be useful for epidemiological research on asthma and could form part of a new standardised questionnaire with wide applications. PMID- 8497819 TI - Lung deposition of nebulised pentamidine in children. AB - BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser. PMID- 8497820 TI - Value of theophylline treatment in patients handicapped by chronic obstructive lung disease. AB - BACKGROUND: It is still not certain whether it is worth using theophylline in addition to inhaled bronchodilators and corticosteroids to treat obstructive airways disease. This trial was designed to test whether the addition of prescribed theophylline in doses sufficient for sustained optimal steady state plasma concentrations would produce any detectable additional advantage in spirometric or functional variables in these handicapped patients. METHODS: A randomised, double blind, placebo controlled, crossover study of added theophylline treatment was aimed at steady state plasma concentrations of 10 and 17 mg/l, the dose being calculated individually by Bayesian parameter estimation and maintained for six weeks along with the patient's previously prescribed bronchodilators and steroids. Of 20 patients sequentially recruited, 15 provided data that could be analysed. All had chronic obstructive lung disease with a mean forced expiratory volume in the first second (FEV1) up to about 30% of the predicted value and gave no history of being treated with theophylline. The protocol included spirometry, whole body plethysmography, and treadmill exercise. Measurements also included steady state plasma theophylline concentrations and trapped gas volume. Quality of life was assessed by an established questionnaire method covering breathlessness in everyday activities, fatigue, emotional function, and control over the disease. RESULTS: Both target plasma concentrations were achieved. Improvements in peak flow (PEF; mean 20%), trapped gas volumes (38%), two stage vital capacity (15%), distances walked (48%), breathlessness in everyday activities (32%), and fatigue (18%) were found at the higher plasma concentration only. FEV1, forced vital capacity (FVC), emotional function, and control did not change. CONCLUSION: Theophylline treatment with sustained steady state concentrations about 17 mg/l provides worthwhile objective and subjective further benefits for patients handicapped by chronic obstructive lung disease when it is added to bronchodilators and corticosteroids. PMID- 8497821 TI - Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function. AB - BACKGROUND: The systemic effects of the inhaled corticosteroid beclomethasone dipropionate are reduced if the drug is inhaled through a large volume spacer. Use of spacers may therefore permit higher doses to be given without causing hypothalamo-pituitary-adrenal suppression. METHODS: Randomised, double blind, double dummy, parallel group study was carried out in adults with chronic asthma to determine the dose of beclomethasone dipropionate causing hypothalamo pituitary-adrenal suppression when the drug was administered by metered dose aerosol with and without a large volume spacer. After a four week run in taking 1.5 mg beclomethasone daily 50 patients underwent tests of hypothalamo-pituitary adrenal function (measurement of 0900 h serum cortisol concentration and 24 hour urinary free cortisol excretion and the short tetracosactrin test). Six patients had hypothalamo-pituitary-adrenal suppression (results of at least two tests subnormal) and asthma was well controlled in six others. Thirty eight patients received increasing doses of beclomethasone with (group S) or without (group MDI) a 750 ml spacer. The daily dose was increased by 0.5 mg at monthly intervals until hypothalamo-pituitary-adrenal suppression developed or a dose of 5 mg/day was achieved. Asthma symptoms and peak expiratory flow were recorded daily. RESULTS: Twenty three patients completed the study, one (group S) reaching a dose of 5 mg beclomethasone dipropionate daily without hypothalamo-pituitary-adrenal suppression. Reasons for withdrawal were poor compliance (n = 10), the patient's decision (n = 3), and asthma that was too unstable (n = 2). "Intention to treat" analysis showed that the median dose of beclomethasone causing hypothalamo pituitary-adrenal suppression was similar in the two groups (3.25 mg in S v 3.0 mg in MDI; 95% confidence interval (CI) for difference -1.0 to 1.0 mg). At 2 mg/day of beclomethasone most patients in both groups had well controlled asthma and there were no differences in symptoms or peak flow between the groups. Good control at this dose did not permit conclusions to be drawn about the efficacy of higher doses. CONCLUSIONS: There is wide interindividual variation in the dose of beclomethasone dipropionate causing hypothalamo-pituitary-adrenal suppression. Whether or not a spacer is used, doses higher than the currently accepted maximum of 2 mg/day can be taken by many adults with asthma without causing subnormal function of the hypothalamo-pituitary-adrenal axis. Whether these higher doses are more effective in controlling asthma remains to be established. PMID- 8497822 TI - Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response. AB - BACKGROUND: The value of measuring airway responsiveness in asthma research is currently limited by the number of different methods used by different investigators, by the lack of a standardised method of expressing precision, and by an inability to equate the results of one method with those of another. METHODS: Two pairs of measurements of airway responsiveness to methacholine were performed in 20 asthmatic subjects, one pair using a dosimeter method (AR-D) and one pair using the conventional Wright nebuliser tidal breathing method (AR-W). The two methods normally use different techniques for quantifying changing levels in forced expiratory volume in one second (FEV1) after each dose of methacholine (the mean of the highest three of six measurements for AR-D, the lower of two measurements for AR-W), and different techniques for expressing measurements of airway responsiveness (the provoking dose (PD20) and the provoking concentration (PC20) respectively responsible for a 20% decrement in FEV1). RESULTS: The coefficient of repeatability (and hence precision) for the measurement of airway responsiveness was significantly better for AR-D (3.0) than for AR-W (10.9), but the technique for quantifying FEV1 contributed more to this than the technique for delivering methacholine. A PC20 of 1 mg/ml with AR-W was equivalent to a PD20 of 103 micrograms with AR-D. CONCLUSIONS: It is practical as well as desirable to compare the precision of different techniques for the measurement of airway responsiveness and to derive conversion factors so that results may be equated. PMID- 8497823 TI - Association of severe asthma attacks with weather, pollen, and air pollutants. AB - BACKGROUND: The association between exacerbations of asthma and weather or air pollution is not well understood. The relationships between visits to the emergency room for asthma attacks and the meteorological, aerobiological, and chemical characteristics of the outdoor air have been evaluated. METHODS: The number of daily attendances for asthma attacks at the emergency room of Oulu University Central Hospital was recorded over one year together with daily meteorological readings (temperature, humidity, barometric pressure, rainfall), levels of air pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), hydrogen sulphide (H2S), total suspended particles (TSP)), and pollen counts (birch, alder, pine, willow, total pollen). The relationship between the number of attendances and the measured variables was then analysed by multiple regression and stepwise discriminant analysis. RESULTS: The total number of attendances during the year was 232, with lower figures in summer and higher in winter. No association was found between visits for asthma attacks and airborne pollen levels or meteorological factors except for temperature, which had a low inverse correlation with attendance. The most significant correlations were found between asthma visits and the levels of NO2; those for SO2, TSP, and H2S were also significant. Intercorrelations between SO2 and temperature or NO2 and between temperature and TSP or NO2 were also found, but only NO2 correlated significantly with attendances after standardisation for temperature. CONCLUSIONS: Increased levels of pollutants, especially NO2, were associated with attacks of asthma, but the explanation for this is unclear. Air pollen levels were not associated with asthma attacks and only temperature among the meteorological factors had a small association with asthma. PMID- 8497824 TI - Relation between response to exercise and diurnal variability of peak expiratory flow in primary school children. AB - BACKGROUND: Variability in peak expiratory flow (PEF) has been proposed as a simple method of screening for asthma in epidemiological studies. This study was designed to assess whether the bronchial response to exercise and the diurnal variation in PEF identified the same subjects. METHODS: Bronchial response to a free running exercise test was assessed in a cohort of 918 seven year old children and was compared with variability of PEF as assessed by twice daily recordings for a one week period. Mini Wright peak flow meters were used throughout the study. RESULTS: Baseline PEFs of both tests were highly correlated but there was no significant correlation between a response to exercise and variability of PEF. Of 33 children with a physician's diagnosis of asthma, 18 had at least one abnormal test, but only five children were abnormal in both tests, showing that the tests did not identify the same subjects. CONCLUSION: Increased variability of PEF, as well as a response to exercise, was associated with respiratory symptoms, but only a response to exercise was closely associated with atopy (defined as a positive skin test to any of seven aero-allergens). PMID- 8497825 TI - Forced oscillation technique and spirometry in cold air provocation tests. AB - BACKGROUND: Impedance measurements by the forced pseudo random noise oscillation technique can be used to study the mechanical characteristics of the respiratory system. The objective of this study was to analyse the changes in impedance to a cold air provocation test in patients with asthma, and to correlate these changes with those in the forced expiratory volume in one second (FEV1). METHODS: The response to isocapnic hyperventilation with cold air was assessed by respiratory impedance measurements and spirometry in 60 patients with bronchial asthma in whom the provocative dose of histamine resulting in a 20% fall in FEV1 (PD20) was < or = 8 mumol. RESULTS: Cold air provocation resulted in a mean(SD) fall in FEV1 from 3.75(0.85) litres to 3.10(0.90) litres. The mean(SD) decrease in FEV1 as a percentage of predicted was 15.4(3.8)%. The oscillatory resistance at 8 Hz increased from a mean(SD) of 0.367(0.108) kPa/l/s to 0.613(0.213) kPa/l/s and at 28 Hz the resistance increased from 0.348(0.089) to 0.403(0.099) kPa/l/s. Frequency dependence of resistance became significantly more negative. The reactance at 8 Hz decreased from a mean(SD) of -0.035 (0.041) kPa/l/s to 0.234(0.199) kPa/l/s, and the resonant frequency increased from 12.5(4.9) Hz to 25.7(9.1) Hz. Significant correlations were calculated between the decrease in FEV1 and changes in the various impedance parameters, especially between the decrease in FEV1 and the increase in resistance at 8 Hz (r = -0.66), and the decrease in FEV1 and the increase in the resonant frequency (r = -0.63). CONCLUSION: Cold air provocation in asthmatic subjects results in changes in the impedance of the respiratory system that correlate well with the changes in FEV1. These changes in impedance reflect ventilatory inhomogeneities in the peripheral compartment of the bronchial tree. These observations show the value of this technique in the evaluation of induced bronchoconstriction, as both a quantitative and a qualitative analysis of the response is possible. PMID- 8497826 TI - Failure of frusemide to increase production of prostaglandin E2 in human nasal mucosa in vivo. AB - BACKGROUND: It has been suggested that inhaled frusemide protects subjects with asthma against bronchoconstriction by enhancing the synthesis of prostaglandin E2 (PGE2). To evaluate this hypothesis the effect of frusemide on PGE2 production from nasal mucosa was studied. METHODS: Two main arachidonic acid metabolites produced by epithelial cells, PGE2 and 15-hydroxy 5,8,11,13-eicosatetraenoic acid (15-HETE), were measured by radioimmunoassay in nasal secretions obtained by nasal lavages with saline. Eleven healthy volunteers were randomly assigned to two study days, one week apart, in a double blind crossover study. Nasal instillation with three increasing doses of frusemide (5, 10, and 20 mg) or placebo was carried out at intervals of 15 minutes. Nasal lavages were performed immediately before nasal instillations and 15, 30, and 60 minutes after the last instillation. RESULTS: Baseline concentrations of 15-HETE were at least six times higher than PGE2. No differences between frusemide and placebo were detected either on PGE2 or 15-HETE release. CONCLUSIONS: The findings do not support the hypothesis that the antiasthmatic effect of frusemide may be due to increased synthesis of PGE2 or release in the respiratory mucosa. PMID- 8497827 TI - Malignant mesothelioma in women. AB - BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos. PMID- 8497828 TI - Model for investigating snorers with suspected sleep apnoea. AB - BACKGROUND: Overnight polysomnography is expensive and time consuming. An approach based on a logistic regression model and overnight pulse oximetry has been developed to determine which of the snorers referred to our sleep laboratory need polysomnography. METHODS: The variables entered in the regression model were derived from questionnaires completed by 95 habitual snorers and 89 patients with obstructive sleep apnoea. The resulting regression equation included weight, height, sex, witnessed episodes of apnoea, and reports of falling asleep when reading. This prediction equation was applied to a sample of 116 consecutive patients referred for investigation of heavy snoring. Pulse oximetry data on the 116 test subjects were obtained during polysomnography and analysed separately. Pulse oximetry was judged to indicate obstructive sleep apnoea when it showed cyclic oscillations of oxyhaemoglobin saturation or heart rate, or both, for more than 30 minutes during the study night. RESULTS: A cut off probability of 0.31 gave the prediction model a sensitivity of 94% to predict an apnoea-hypopnoea index above 10, with a specificity of 45%. When this cutoff point was used to predict an apnoea-hypopnoea index of over 20 sensitivity was 95% and specificity 41%. Combined with oximetry our regression model had a sensitivity of 100% for predicting an apnoea-hypopnoea index of more than 10. On the other hand, all patients with negative results from oximetry and a probability value below 0.31 had an apnoea-hypopnoea index lower than 10 according to polysomnography. CONCLUSIONS: It is concluded that snorers with negative results from oximetry classified as not having obstructive sleep apnoea according to this model do not need polysomnography. PMID- 8497829 TI - Evaluation of a computerised polysomnography system. AB - BACKGROUND: Manual analysis of sleep, breathing, and oxygenation records is the "gold standard" for diagnosing sleep abnormalities but is time consuming and cumbersome. The accuracy and cost of a computerised sleep analysis system have therefore been investigated. METHODS: Manual and computerised (CNS Sleep Lab) scores from 43 consecutive clinical sleep studies were prospectively compared for accuracy and the time and costs were recorded. RESULTS: There were good correlations and no systematic differences between manual and computer scoring for total sleep time, sleep onset latency, and duration of REM sleep. There was a small but clinically insignificant systematic difference in breathing pattern analysis, the number of hypopnoeas/hour being lower with manual than with computer scoring (13 (SE 3) v 15 (SE 3)/hour). There was no difference between computer and manual scoring of the frequency of apnoeas, so the frequency of apnoeas + hypopnoeas was clinically insignificantly higher with computer scoring with a highly significant correlation between the two techniques. The time taken to perform the analyses was not different between the two methods (manual 83 (SE 8) v computer 86 (SE 8) minutes). The computer system was six times more expensive than the manual system and annual running costs, including full maintenance contract and 15% depreciation, were twice as great. CONCLUSION: The CNS Sleep Lab is sufficiently accurate for use in clinical sleep studies but is significantly more expensive and does not save technician time. PMID- 8497830 TI - Deaths and necropsies in a thoracic unit. AB - BACKGROUND: There is concern about the decrease in the number of requests for necropsies, so a study was undertaken to assess current clinical practice. METHOD: A prospective study was made of all deaths occurring under the care of five chest physicians and three thoracic surgeons at East Birmingham Hospital from 1 April to 30 June 1989. RESULTS: A necropsy was sought in 34 of 58 deaths (59%) and was performed in 22 instances (38%). Major unexpected findings which would have affected clinical management were noted in three patients (14%). The mean delay in reporting results of histological examinations was 146 days (range 41-260 days). As the result of an increase in pathology technical staff levels and alteration in the practice of processing histological data, there was a substantial improvement during the corresponding period in 1990 (mean reduction 58 days, 95% confidence limits 39-77 days). Apart from patients with histologically proved carcinoma, there was no consistent pattern for requests for necropsies. CONCLUSIONS: Necropsies continue to reveal diagnoses which were not suspected while the patient was alive. Although the number of requests made by clinical staff for necropsies is reasonable, the reasons for the requests are not consistent. Guidelines are suggested to improve the number of successful requests and to maximise the information obtained from them. PMID- 8497831 TI - Effect of oral bronchodilators on lung mucociliary clearance during sleep in patients with asthma. AB - BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group's previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep. PMID- 8497832 TI - New perspectives on basic mechanisms in lung disease. 4. Why are the airways so vascular? PMID- 8497833 TI - Intrathoracic vagus nerve neurofibroma and sudden death in a patient with neurofibromatosis. AB - A 21 year old man with type 1 neurofibromatosis was found dead in the middle of the night. Postmortem examination revealed a large neurofibroma arising from the right intrathoracic vagus nerve, which might have contributed to his sudden death. PMID- 8497834 TI - Inhalation trauma due to overheating in a microwave oven. AB - The microwave oven is a kitchen appliance that has become increasingly popular in recent years. In some instances the temperature in the microwave oven can become exceedingly high. A case is discussed of a patient with respiratory distress after inhalation of gas from an overheated microwave oven. PMID- 8497835 TI - Management of pulmonary embolism. PMID- 8497836 TI - Management of pulmonary embolism. PMID- 8497837 TI - Does a positive Heaf test reaction in Asian schoolchildren predict later breakdown of tuberculosis? PMID- 8497838 TI - National survey of notifications of tuberculosis in England and Wales in 1988. PMID- 8497839 TI - Tuberculosis contact tracing: are the British Thoracic Society guidelines still appropriate? PMID- 8497840 TI - Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis. AB - We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497841 TI - Problems of oral anticoagulation in an adult with homozygous protein C deficiency and late onset of thrombosis. AB - We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder. PMID- 8497842 TI - Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. AB - This study evaluated the advantage of an anticoagulation clinic in terms of the improvement of the clinical quality of oral anticoagulation (i.e. prevention of thromboembolism and low rate of hemorrhagic complications). The incidence of thromboembolic events and major hemorrhagic complications was assessed in a series of 271 patients on oral anticoagulation for mechanical heart valve prosthesis before and after their enrollment in our anticoagulation clinic from January 1987 to December 1990. Risk factors for hemostatic events were also analyzed. The incidence of major hemostatic complications was significantly lower when patients attended the clinic: 1.0 vs 4.9%/pt-yr for hemorrhage and 0.6 vs 6.6%/pt-yr for thrombosis. This depended on three main factors: better dose regulation of warfarin, continuous patient education and early identification of clinical conditions potentially at risk for thrombosis and hemorrhage. Only previous hemorrhagic or thromboembolic events were recognized as major risk factors for hemostatic complications. In conclusion, our study shows that an anticoagulation clinic offers a real advantage to patients with mechanical heart valve prosthesis in terms of prevention of thromboembolic events and hemorrhagic complications. PMID- 8497843 TI - Influence of acute myocardial infarction and rt-PA therapy on circulating fibrinogen. AB - In 12 patients treated with 100 mg rt-PA/3 h for acute myocardial infarction (AMI), serial fibrinogen levels were measured with the Clauss clotting rate assay ("functional fibrinogen") and with a new enzyme immunoassay for immunologically intact fibrinogen ("intact fibrinogen"). Levels of functional and "intact fibrinogen" were strikingly different: functional levels were higher at baseline; showed a more pronounced breakdown during rt-PA therapy; and a rebound phenomenon which was not seen for "intact fibrinogen". The ratio of functional to "intact fibrinogen" was calculated for each individual patient and each time point. The mean ratio (n = 12) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (p < 0.01), indicating that functionality of circulating fibrinogen changes during AMI and subsequent thrombolytic therapy. The increased ratio of functional to "intact fibrinogen" seems to reflect a more functional fibrinogen at baseline and following rt-PA infusion. This is in keeping with data that the relative amount of fast clotting "intact HMW fibrinogen" of total fibrinogen is increased in initial phase of AMI. The data suggest that about 20% of HMW fibrinogen are converted to partly degraded fibrinogen during rt-PA infusion. The rebound phenomenon exhibited by functional fibrinogen may result from newly synthesized fibrinogen with a high proportion of HMW fibrinogen with its known higher degree of phosphorylation. Fibrinogen- and fibrin degradation products were within normal range at baseline. Upon infusion of the thrombolytic agent, maximum median levels of 5.88 micrograms/ml and 5.28 micrograms/ml, respectively, were measured at 90 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497844 TI - A sensitive peroxidase staining immunoblotting method for measuring total protein S in human plasma. AB - In plasma, protein S is found in its free form and as a complex with C4b-binding protein. After 125I-protein S was added to normal human plasma and applied to SDS 8% polyacrylamide gel electrophoresis, the autoradiogram of the gel showed only one single band at free protein S position. Applying this evidence, we have developed a peroxidase staining Western Blotting method to quantitate total protein S in human plasma which consists of sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by blotting to nitrocellulose membrane and a sensitive avidin-biotinylated peroxidase staining method (ABC technique). The measurement of protein S by the immunoblotting was reproducible and the coefficient of variation was 7%. As little as 1 ng of protein S could be detected. C4b-binding protein did not affect the measurement of protein S. Compared to other immunoassays, this peroxidase staining immunoblotting method has the advantage of directly estimating the apparent molecular weight of protein of interest, eliminating nonspecific stain and having high sensitivity without using radioisotope. PMID- 8497845 TI - Different expression of procoagulant activity in human cancer cells cultured "in vitro" or in cells isolated from human tumor tissues. AB - We studied in a homologous system the procoagulant activity of human tumor cells cultured "in vitro" (1402 primary melanoma, Me 7110/2 metastatic melanoma, Hep G2 hepatoma and GLC1 small cell lung carcinoma) or of cells freshly isolated from different human tumor tissues. Tumor cells cultured "in vitro" possessed and released a factor VII dependent procoagulant activity, which was inhibited by concanavalin A and unaffected by iodoacetamide or HgCl2. The activity released by the cells of metastatic melanoma was higher than that released by the cells of the primary tumor. On the contrary, cancer cells isolated from tumor tissues possessed and released a factor VII independent activity which was inhibited by iodoacetamide of HgCl2 and was not modified by concanavalin A. Therefore, different methods for the preparation of tumor cell suspensions have to be used for the study of tumor procoagulants, since their expression depends very largely on the source of tumor cells. Furthermore, cultured human tumor cells are not an appropriate model for the "in vivo" procoagulant effect of tumor cells. PMID- 8497846 TI - The pharmacokinetics of LMW dermatan sulphate: long-term persistence of intact material. AB - An iodinated derivative of the low molecular weight dermatan sulphate Desmin 370 was administered to rats by intravenous, subcutaneous and intramuscular routes in conjunction with unlabelled Desmin 370. Following intravenous injection radiolabel was cleared from the plasma according to a tri-exponential function with elimination half-lives of 45 min and 13 h; there was a high concentration in tissues, particularly the kidney, compared with plasma. The apparent bioavailability following s.c. injection was 52-65%, but 84-100% after i.m. administration. Undegraded as well as desulphated molecules were identified in plasma, and intact 125I-Desmin 370 comprised > 85% of the radiolabel in urine 48 h post-injection. Thus intact Desmin 370 persists for a long period after a single injection. The pharmacological significance of these findings, however, remains to be determined. PMID- 8497847 TI - The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. AB - The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors. PMID- 8497848 TI - Diversity of primary structures of the carboxy-terminal regions of mammalian fibrinogen A alpha-chains. Characterization of the partial nucleotide and deduced amino acid sequences in five mammalian species; rhesus monkey, pig, dog, mouse and Syrian hamster. AB - The partial amino acid sequences of fibrinogen A alpha-chains from five mammalian species have been inferred by means of the polymerase chain reaction (PCR). From the genomic DNA of the rhesus monkey, pig, dog, mouse and Syrian hamster, the DNA fragments coding for alpha-C domains in the A alpha-chains were amplified and sequenced. In all species examined, four cysteine residues were always conserved at the homologous positions. The carboxy- and amino-terminal portions of the alpha-C domains showed a considerable homology among the species. However, the sizes of the middle portions, which corresponded to the internal repeat structures, showed an apparent variability because of several insertions and/or deletions. In the rhesus monkey, pig, mouse and Syrian hamster, 13 amino acid tandem repeats fundamentally similar to those in humans and the rat were identified. In the dog, however, tandem repeats were found to consist of 18 amino acids, suggesting an independent multiplication of the canine repeats. The sites of the alpha-chain cross-linking acceptor and alpha 2-plasmin inhibitor cross linking donor were not always evolutionally conserved. The arginyl-glycyl aspartic acid (RGD) sequence was not found in the amplified region of either the rhesus monkey or the pig. In the canine alpha-C domain, two RGD sequences were identified at the homologous positions to both rat and human RGDS. In the Syrian hamster, a single RGD sequence was found at the same position to that of the rat. Triplication of the RGD sequences was seen in the murine fibrinogen alpha-C domain around the homologous site to the rat RGDS sequence. These findings are of some interest from the point of view of structure-function and evolutionary relationships in the mammalian fibrinogen A alpha-chains. PMID- 8497849 TI - Distribution of tissue factor pathway inhibitor in normal and malignant human tissues. AB - Specific antibodies to tissue factor pathway inhibitor (TFPI) were used in immunohistochemical procedures to determine the distribution of TFPI in normal and neoplastic human tissues. TFPI was restricted to megakaryocytes and the endothelium of the microvasculature in normal and abnormal tissues, but was not found in the endothelium of larger vessels or in hepatocytes. TFPI was also detected in macrophages in the villi of term placenta. Tumor-associated macrophages in several types of malignancy that we have shown previously to express a complete tissue factor-initiated pathway of coagulation and thrombin generation also manifested TFPI. By contrast, malignant cells in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma that we have shown previously to express coagulation factors together with tumor cell associated fibrin formation failed to stain for TFPI. We postulate that TFPI may be lacking from the latter malignancies because of the absence of the appropriately configured tissue factor-factor VIIa-factor Xa complex required for TFPI binding. PMID- 8497850 TI - Recombinant pro-urokinase requires heparin for optimal clot lysis and restoration of blood flow in a canine femoral artery thrombosis model. AB - Heparin is often used as an adjunct to thrombolytic therapy in order to prevent reocclusion of the patent vessels in patients with thrombotic disease. Controversy exists as to whether heparin is required for effective clot lysis with tissue-type plasminogen activator, while in vitro data and small scale clinical trials have suggested an enhancement of pro-urokinase efficacy by heparin. The present study was conducted to determine whether heparin pre treatment is required to produce optimal clot lysis and blood flow restoration in response to recombinant pro-urokinase (r-proUK). In four groups of dogs, blood clots labelled with 125Iodine were formed in the femoral artery and were monitored continuously for loss of counts as an indicator of clot lysis. Femoral artery blood flow was measured simultaneously. Group 1 received vehicle (n = 5), while group 2 was given vehicle + heparin (n = 6; 500 U bolus + 350 U/h). This dose of heparin increased the activated partial thromboplastin time (APTT) by at least 1.5 times the control level for the 4 h observation period. Group 3 received r-proUK alone at a dose of 100,000 U/kg (50% given as a 1-min bolus injection, 50% as a 30 min infusion) (n = 8), while group 4 was treated with the same dose of r-proUK in the presence of heparin as described (n = 8).2 PMID- 8497851 TI - Retinoic acid enhances fibrinolytic activity in-vivo by enhancing tissue type plasminogen activator (t-PA) activity and inhibits venous thrombosis. AB - We studied the profibrinolytic effect and the anti-thrombotic potential of retinoic acid in-vivo. Male Wistar rats were treated with retinoic acid either acutely or twice daily for a period of 5 consecutive days in a dose range of 0.01 to 3.0 mg/kg. Fibrinolytic activity was measured ex-vivo using the diluted blood clot lysis test and net t-PA activity in tissue extracts was measured in a spectrophotometric rate assay. Clot lysis was dose dependently increased by retinoic acid up to about 170% (relative to vehicle treated rats) at a dose of 3 mg/kg. No tachyphylaxis could be detected. Ex-vivo measured fibrinolytic activity after single administration of 1 mg/kg of retinoic acid peaked at 3 h after ingestion. Even after 18 h a significantly higher clot lysis rate was measured. Lysis of blood clots from vehicle and retinoic acid treated rats could be completely blocked by addition of tranexamic acid or antibodies against rat t-PA before clot formation. t-PA activity in plasma was slightly increased after retinoic acid treatment; no effects were measured on plasma PAI-1, u-PA, plasminogen, and alpha 2-antiplasmin levels. t-PA activity in lung and kidney was marginally enhanced by retinoic acid but in heart and aortic tissue extracts t-PA activity was increased by about 50%. We confirmed this potential anti-thrombotic property in an in-vivo venous thrombosis model. A reduced clot size was observed after retinoic acid administration (35% reduction at a dose of 1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8497852 TI - Role of urokinase type plasminogen activator (u-PA) in corneal epithelial migration. AB - The role of plasminogen activator (PA) in the migration of corneal reepithelialization was studied. Rabbit corneal blocks were cultured, and both the extent of epithelial migration over the exposed corneal stroma and the activity of PA released into the culture media were measured. A significant, direct correlation between epithelial migration and PA activity in the medium was observed, even when the migration was stimulated by fibronectin or EGF, or was inhibited by cytochalasin B or cycloheximide. Zymography confirmed that the PA released into the culture medium was of the urokinase type (u-PA). Immunohistochemical studies showed that u-PA and plasmin(ogen) were present at the leading edge of the migrating epithelium. Studies of corneal cell cultures indicated that epithelial cells rather than endothelial cells or fibroblasts were the source of the u-PA. The addition of antihuman u-PA IgG or protease inhibitors retarded the migration of the corneal epithelium in a dose-dependent manner, indicating that u-PA activity is essential for the migration of the corneal epithelium. These findings suggest that the migration of corneal epithelial cells requires not only cell attachment to the extracellular matrix through the fibronectin but also degradation of the fibronectin by the release of cellular u PA. PMID- 8497853 TI - Two novel mutations at 373 codon of FVIII gene detected by DGGE. PMID- 8497854 TI - Single step purification of platelet factor XIII using an immobilized factor XIII a-subunit monoclonal antibody. AB - To facilitate the analysis of the catalytic subunit of factor XIII we have developed a method for the immunoaffinity purification of this protein from platelets. This method employs a monoclonal antibody that binds to the a-subunit of factor XIII. The anti-factor XIII antibody was immobilized on agarose and then incubated with platelet lysate. Subsequently factor XIII was isolated from the platelet lysate in a single step with a 41% yield as measured by enzyme assay. The purified platelet factor XIII appeared nearly homogeneous when analyzed by polyacrylamide electrophoresis and by immunoblotting with another factor XIII monoclonal antibody. PMID- 8497855 TI - Endothelin: a possible role in the occurrence of renal failure in thrombotic thrombocytopenic purpura. PMID- 8497856 TI - Factor VIII inhibitor associated with ciprofloxacin. PMID- 8497857 TI - Fibrinogen internalization by ADP-stimulated blood platelets. Ultrastructural studies with fibrinogen-colloidal gold probes. AB - Interaction of gel filtered, ADP-stimulated human platelets with low (0.05 mg/ml) and high (1 mg/ml) fibrinogen (Fg) was examined by transmission electron microscopy. To visualize exogenous Fg in a course of its interaction with stimulated platelets, Fg coupled to 18-nm colloidal gold (Fg-Au) was employed. In the presence of either Fg or Fg-Au, rapid changes of platelets morphology indicative of resting to activated state transition, were observed. Without external ligands, stimulated platelet suspensions resemble rather control (untreated) samples. Using Fg-Au, it has been found that initial binding of gold labels to platelet surfaces is immediately followed by gold accumulation in plasmalemma pits subjected to further internalization. Serial sections proved that at 1 min, some of the labeled endocytic structures are already isolated in the platelet cytoplasm. After prolonged (20 min) incubations, different platelet subfractions have been found. Many single or loosely aggregated platelets with little or no surface labeling contained abundant stores of internal labels. In these cells, Fg-Au is localized in vacuole-like and/or granule-like structures. Some post-stimulated (discoidal) platelets are likely to release Fg-Au previously internalized. In the centers of platelet aggregates concentrated labels filled intercellular spaces and voluminous intraplatelet cavities, either open or occluded. These results indicate on different ultimate fates of exogenous Fg processed by the ADP-stimulated platelets. The data obtained suggest also that after initial binding, exogenous Fg may be implicated not only in aggregation, but in activation-related cellular responses as well. PMID- 8497858 TI - Circadian variation of plasminogen activator activity, plasminogen activator inhibition and plasmin inhibition in aorta, heart, brain and lungs of the rat. Sex-related differences. AB - Plasminogen activator activity (PAA), t-PA antigen level, plasminogen activator inhibition (PAI) and plasmin inhibition (PI) showed a circadian variation in rat aorta, heart, brain, and lungs of both sexes, but in a different way depending on the organ and the fibrinolytic parameter studied and the sex as well. In general, the lowest values of PAA and t-PA antigen were found in the early morning and the highest values in late afternoon, while PAI or PI showed the opposite pattern (with the exception of lungs). In kidneys and liver the fibrinolytic parameters studied showed no circadian variation. Sex-related differences, mostly quantitative, were noted in aorta, heart, brain and kidneys, with lower PAA and t PA antigen and higher PAI or PI in the male than in the female. PMID- 8497859 TI - Functional studies on platelets of a patient with an acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIB/IIIA complex. AB - Platelet functions have been studied of a 63 year old woman with a severe acquired thrombopathy. The platelets did not adhere to siliconized glass. Aggregation could not be induced by either ADP (1 microM) nor collagen (2 micrograms/ml), no release of serotonin was found under these conditions. Thrombin caused only a weak aggregation response. Quantitative analysis of platelet actin revealed a very low total actin content (473 micrograms/10(9) platelets) and an extremely low F-actin value (3% of total actin). Stimulation of platelets with 0.1 U/ml thrombin for 3 min resulted in an increase of only 5% F actin, whereas ADP and collagen did not induce any actin polymerization. Ca2+ movement in the patient's platelets is severely impaired after ADP and collagen stimulation, whereas a normal Ca2+ movement was obtained by 0.1 U/ml thrombin. The inhibition of the functions of normal platelets (aggregation and actin polymerization) by addition of patient's serum (5-10% final concentration) points to receptor blockade by platelet autoantibodies in the patient's serum. The antibody was purified by adsorption on Protein-A-Sepharose. Addition of IgG suspension (5% final concentration) to washed control platelets resulted in similar effects on aggregation and actin polymerization compared to the effects of patient's serum. PMID- 8497860 TI - alpha-Thrombin within fibrin clots: inactivation of thrombin by antithrombin-III. AB - To demonstrate that human alpha-thrombin is effectively inactivated by human antithrombin III (AT) during the production of a fibrin clot we measured the amount of alpha-thrombin activity which can be recovered from a clot generated from purified human proteins. We discovered that 0.05-0.07% of the original alpha thrombin activity is recovered from a fibrin clot produced from a reaction mixture where the initial concentrations of AT and alpha-thrombin were chosen at a ratio (17.5) to allow complete conversion of fibrinogen to fibrin. These results indicated that alpha-thrombin is successfully inactivated by AT during the production of a fibrin clot. Further, when an amount of alpha-thrombin equal to that recovered from a fibrin clot is introduced into a solution of fibrinogen and AT identical to that utilized to produce the clot only 4% of the fibrinogen is converted to fibrin. These results suggest that i) when a fibrin clot is dissolved during fibrinolytic therapy little active alpha-thrombin should be released from the clot and ii) this amount of thrombin is insufficient to catalyze rethrombosis without proposing de novo production of thrombin. The action on factors XI, VIII, and V of the small amount of thrombin released upon thrombolysis, however, may provide the stimulus for de novo production of sufficient thrombin to catalyze rethrombosis. PMID- 8497861 TI - Correlation of light transmission changes to changes of platelet glycoprotein Ib during storage of platelet concentrates. AB - The present study compares some properties of platelet concentrates, i.e. their ability to transmit light and the degree of platelet lysis and the deterioration of the platelet membrane glycoprotein Ib (GPIb). Extracellular levels of glycocalicin and lactate dehydrogenase (LDH) served as indicators for the proteolytic cleavage of GPIb and platelet lysis, respectively. The light transmission of 16 platelet apheresis concentrates was monitored continuously during storage using a specially designed apparatus. Determination of platelet counts and extracellular glycocalicin levels was carried out on day 1. In addition, after 7 days of storage extracellular concentrations of LDH and glycocalicin were determined. After 7 days highly significant correlations were found both when comparing light transmission changes and extracellular glycocalicin levels (r = 0.78; p < 0.001) and when comparing light transmission changes and extracellular concentrations of LDH (r = 0.83; p < 0.001). PMID- 8497862 TI - Effects of lipoprotein(a) on in vitro lysis of whole blood thrombi from healthy volunteers. AB - Elevated levels of lipoprotein(a) [Lp(a)] were shown to be an independent cardiovascular risk factor. Structural homologies between Lp(a) and plasminogen could be of importance for this. In the present study, the influence of Lp(a) on in vitro lysis of thrombi produced in recalcified whole blood was investigated. Of 120 healthy volunteers, 21 (18%) had serum Lp(a) levels > or = 25 mg/dl (median 70 mg/dl). Compared to 46 controls with serum Lp(a) < 25 mg/dl (median 7 mg/dl), the weight of whole blood thrombi generated in vitro was similar (96 +/- 11 vs. 94 +/- 13 mg). Thrombolysis with exogenously added tissue plasminogen activator (TPA; 0.1, 0.4 and 1.6 mg/l) was not affected by the ex vivo concentration of Lp(a). In persons with elevated Lp(a), plasma TPA levels were higher than in persons with low Lp(a) [15.7 +/- 1.5 vs. 11.7 +/- 1.2 micrograms/l; p = 0.051], but plasminogen activator inhibitor (PAI) activity and the plasma concentrations of PAI-1 were also higher. When Lp(a) was added in vitro to blood with low baseline Lp(a) [median final concentration 47 mg/dl], thrombolysis was significantly inhibited with low doses of TPA (0.1 and 0.4 mg/l), but remained unaffected with TPA 1.6 mg/l. Thus, the inhibitory effect of Lp(a) on thrombolysis seems to be counterregulated in blood of healthy volunteers with elevated Lp(a). PMID- 8497863 TI - Detection of antiphospholipid antibodies in heat inactivated normal human sera. PMID- 8497864 TI - Environmental exposure to cadmium and human birthweight. AB - Fetal toxicity of cadmium (Cd) is well documented in rodents. However, little information is available regarding the human fetus. To investigate the effect of low levels of Cd on the human placenta and the consequences on birthweight, we conducted a study of 102 mothers and their newborns in an obstetrical care unit. Placental and hair samples were collected at delivery to determine Cd concentrations. The main finding of this study was the relationship between a decrease in birthweight and an increase of newborn hair Cd which varied in the presence of placental calcification. In cases of parenchymal calcifications, placental Cd levels were higher (Wilcoxon test, P < 0.05) and newborn hair Cd levels were lower (Wilcoxon test, P < 0.01) than in the absence of calcification. These relationships remained significant even after taking into account smoking habits and gestational age. In the presence of calcification, an increase in the level of Cd in newborn hair was related to a decrease in birthweight which was independent of placental Cd concentration (rpartial = -0.49, P < 0.01). In the absence of calcification, a decrease in birthweight was observed for the upper values of newborn hair Cd (r = -0.44, P < 0.05 when Cd > or = 0.3 ppm). The difference in birthweight between infants in the first and last quartiles of newborn hair Cd was 472 g in cases of calcifications and 122 g in the absence of calcification. Other placental parameters were not significantly related to placental Cd concentration. PMID- 8497865 TI - Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat. AB - Subcutaneous injections of mercuric chloride induce an autoimmune glomerulonephritis with both granular and linear IgG deposits along the glomerular capillary wall and proteinuria. This disease is due to a T cell dependent polyclonal B cell activation responsible for production of antibodies against self (glomerular basement membrane, immunoglobulins, DNA, myeloperoxydase) and non self (sheep red blood cells, trinitrophenol (TNP)) components. Increase in serum IgE concentration is the hallmark of this disease. To determine if mercury vapours have pathogenic effects is an important problem of public health. The aim of this study was, first to compare the effects of mercury vapour exposure to those of mercury injections and, second, to compare the effects of high doses to those of low doses of mercury. Two exposure levels were studied corresponding to a mercury absorption of 13.1 mumol/week per kg body wt. and 1.7 mumol/week per kg body wt. during a 5-week period. It will be shown that, whereas the mercury concentration in the kidneys was similar in injected- and vapour exposed--rats, the mercury concentration in blood at the end of the exposure was about twice as high in the injected animals. Blood concentration of mercury was related to dose level but kidney content of mercury was similar in all groups, in spite of a dose difference by a factor of seven between low and high exposure. Mercury vapour and HgCl2 injections both trigger autoimmunity to the same extent and, in both cases the extent of autoimmune manifestations was dose-dependent. PMID- 8497866 TI - Induction of a 70-kDa protein in human lymphocytes exposed to inorganic heavy metals and toxic organic compounds. AB - Human peripheral blood lymphocytes synthesize a 70-kDa protein (p70) distinct from metallothionein (MT), in response to several inorganic heavy metals. Although Cd and Zn induce both p70 and MTs, Co induces only p70. On the other hand, Cu, Hg, Ni and Ag, which are the inducers of MTs, can not induce p70. This protein is indistinguishable in electrophoretic mobility from the 70-kDa heat shock protein, which is induced by incubation of lymphocytes at 42-45 degrees C. Several environmental pollutants other than the inorganic heavy metals, including organic tin compounds and organic phosphorus compounds, were also found to induce p70. The responsiveness to a variety of environmental stimuli suggests the involvement of p70 in the basic cellular defense mechanism. PMID- 8497867 TI - Effect of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide on renal function and hemodynamics in the anesthetized rat. AB - The experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is a nephrotoxicant in the Fischer 344 rat. NDPS induces nephrotoxicity via metabolic bioactivation to one or more metabolites. Both N-(3,5-dichlorophenyl)-2 hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA), oxidative metabolites of NDPS, are more potent nephrotoxicants than the parent compound. Preliminary studies in our laboratory indicate that altered renal hemodynamics may contribute to the mechanism of NDPS-induced nephrotoxicity. However, it is not known if NDPS affects renal hemodynamics prior to or after altering tubular function. In this study, male Fischer 344 rats (275 300 g) were anesthetized with urethane (1.5 g/kg, i.p.) and prepared for renal function experiments. Renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V) and fraction of GFR excreted as urine (V/GFR) were determined during eight 30 min intervals following NDHS (0.2 or 0.4 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/kg, i.p.) treatment. NDHS (0.2 or 0.4 mmol/kg) decreased GFR while urine flow rate and V/GFR were increased compared to vehicle treated controls. These alterations in renal function were evident by 2 h post NDHS (0.4 mmol/kg) and by 3 h post-NDHS (0.2 mmol/kg) treatment. RBF of rats receiving NDHS (0.2 or 0.4 mmol/kg) tended to decrease post-NDHS treatment; however, this decrease was not significant. Results of this study indicate that NDHS (0.2 or 0.4 mmol/kg) initially alters renal function by reducing the tubular reabsorption of glomerular filtrate prior to a reduction of GFR and RBF. PMID- 8497868 TI - Effectiveness of sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) in protecting against uranium-induced developmental toxicity in mice. AB - The effect of Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent used in the treatment of experimental poisoning by a number of heavy metals, on uranium-induced developmental toxicity was evaluated in Swiss mice. A series of four Tiron injections was administered intraperitoneally to pregnant mice immediately after a single subcutaneous injection of 4 mg/kg of uranyl acetate dihydrate given on day 10 of gestation and at 24, 48, and 72 h thereafter. Controls received 0.9% saline with or without uranyl acetate. Tiron effectiveness was assessed at 500, 1000 and 1500 mg/kg per day. Amelioration by Tiron of uranium-induced embryolethality was not noted at the two lower doses. The percentage of dead and resorbed fetuses in the Tiron-treated groups was not statistically different from that in the positive control group. However, treatment at 1500 mg/kg per day showed isolated protective effects against uranium fetotoxicity, such as that evidenced by the lack of differences in fetal body weight between this group and the uranium-untreated group, as well as by a decrease in the number of skeletal defects. According to these results, the ability of Tiron to protect the developing mouse fetus against uranium-induced developmental toxicity offers only modest encouragement with regard to its possible therapeutic potential for pregnant women exposed to this metal. PMID- 8497869 TI - Malaoxon-induced neurotoxicity in old rats: alterations in cerebral inositol lipid signalling, brain tissue calcium levels and early neuronal injury. AB - Effects of malaoxon (MO) on brain regional inositol, inositol monophosphate and calcium levels, as well as on early neuronal injury, were studied in old (18 months) male rats. In old rats, a dose of 8.7 mg/kg of MO caused convulsions similar to those reported earlier in parallel experiments with young male (10 weeks) rats using a dose of 39.2 mg/kg. In the convulsing old male rats, MO caused a transient decrease of cerebral inositol 1 h post MO in the piriform cortex and thalamus, whereas more persistent decreases of inositol occurred in the frontal cortex and the cerebellum. In the non-convulsing rats, a decrease of inositol was only seen in the cerebellum. Cerebral inositol-1-phosphate (Ins1P) increased in all brain regions of convulsing rats, whereas Ins1P did not change in the non-convulsing rats. Brain Ca2+ increased post MO in convulsing and non convulsing rats in the frontal cortex, caudate and thalamus; in the piriform cortex and hippocampus increases of Ca2+ were only seen in the convulsing rats. Inositol-4-phosphate (Ins4P) remained stable in all MO-exposed rats. MO-induced early neuronal injury occurred only in the convulsing rats and was most severe in the cortex, hippocampus and the subcortical structures. Qualitatively the effects of MO in the old and young rats were, however, similar and, therefore, probably due to cholinergic brain stimulation and subsequent increase in inositol lipid signalling. These results suggest that old rats are likely to be more sensitive than the young rats to the neurotoxic effects of MO. PMID- 8497870 TI - Nephrotoxicity of borocaptate after short-term administration in rabbits. AB - Fifteen Chinchilla rabbits were treated by seven daily i.v. injections of two doses (25 or 50 mg/kg body wt.) of sodium borocaptate (Na2B12H11SH), an agent now widely investigated for potential use in Boron Neutron Capture Therapy (BNCT) of malignant brain tumors. Definite nephrotoxic lesions hyperemic and dilated glomeruli, degenerative necrobiosis with desquamation of tubular epithelium, granular casts in the distal convoluted and collecting tubuli were detected by histopathological examination in the kidneys of all animals without relation to dose of borocaptate. The accumulation of urea in blood and a reduction in red blood cell counts were, however, statistically significant only in rabbits receiving the higher dose (50 mg/kg body wt.) of borocaptate. In the brain the prevalent finding was dilation of perivascular (Virchow-Robin's) spaces. The growth of the animals was retarded and three animals died after injection of the 5th daily dose of borocaptate. With respect to these findings borocaptate sodium can by no means be regarded as an agent which is fully devoid of activity towards healthy non-tumor tissue. Therefore, recent proposals to enhance the effectiveness of BNCT by repeated borocaptate treatment should be considered with caution. PMID- 8497871 TI - Cyclosporine-ketoconazole interaction. Long-term follow-up and preliminary results of a randomized trial. AB - Forty-three renal transplant recipients receiving cyclosporine were started on 200 mg/day of oral ketoconazole 10 days to 75 months posttransplant. The cyclosporine dose was reduced by 70% when ketoconazole was started. The mean cyclosporine dose was 5.6 mg/kg/day preketoconazole, and 0.9, 0.8, and 0.7 mg/kg/day at one, two, and three years after addition of ketoconazole (cyclosporine dose reduction 84%, 86%, and 88% at one, two, and three years, respectively). Two patients died after two years of combination therapy, six patients returned to dialysis, and ketoconazole was discontinued in four. Renal function in patients on ketoconazole remained stable (serum creatinine 1.8, 1.7, 1.7, and 1.8 mg/dl preketoconazole and at one, two, and three years, respectively). In a second study, 52 patients were randomized to standard doses of cyclosporine (n = 28), or reduced doses of cyclosporine with ketoconazole (n = 24); seven of the patients were not started on ketoconazole. In 28 patients on standard-dose cyclosporine, there were two deaths and one graft loss. In 17 patients receiving ketoconazole there were two deaths and no graft losses. Renal function and the frequency of rejection episodes was similar in the two groups. In the ketoconazole group, the cyclosporine dose was < 20% of that in the patients on standard doses. In both studies addition of ketoconazole to cyclosporine-treated patients resulted in significant inhibition of cyclosporine metabolism and decrease in dosage in patients followed for up to four years. This drug interaction provides a significant reduction in cost of immunosuppressive therapy in organ transplant recipient. PMID- 8497872 TI - Six-antigen-matched transplants. Causes of failure. AB - The causes of failure were studied for 1386 cadaver kidney transplants shared through the UNOS 6-antigen match program from November 1987 to February 1992. The one-year graft survival for 1004 HLA-matched first cadaver transplants was 88% compared with 90% for parent donor and 78% for 22,188 HLA-mismatched first cadaveric donors reported to the UNOS Scientific Renal Transplant Registry. The cause of graft loss was immunological in 55% of HLA-mismatched cadaver kidney failures, whereas only 39% of the HLA-matched graft failures were immunological. The fraction of immunological failures in HLA-matched first transplant recipients younger than age 17 was 57% and decreased with increasing age to 14% for recipients older than age 60. Death with a functioning graft accounted for 50% of failures in the older age group. Sensitization was associated with an increased incidence of immunological failures in matched first graft recipients from 36% in nonsensitized to 53% in broadly sensitized patients, and 55% of failures were immunological in second graft recipients compared with 39% in first transplants. Some immunological failures may have been due to tissue typing, since only 18% of failures in kidneys with well-defined HLA antigens were immunological, whereas 44% of kidneys matched with more difficult HLA antigens were lost due to immunological causes. The results indicate that phenotypically identical cadaver renal transplants have a reduced rate of immunological failures. As the accuracy of this tissue typing for the more difficult HLA antigens improves, immunological failures in this group of transplants will decline even further. PMID- 8497873 TI - Excellent outcome with a calcium channel blocker-supplemented immunosuppressive regimen in cadaveric renal transplantation. A potential strategy to avoid antibody induction protocols. AB - Many transplant centers routinely utilize monoclonal antibody or polyclonal antibody based induction protocols in recipients of cadaver renal allografts. Given the potential complications associated with antibody-based immunosuppression regimens (e.g., CMV disease), we tested the hypothesis that a combination of a calcium antagonist and a triple drug protocol (cyclosporine + prednisone + azathioprine) would be an effective substitute for antibody-based induction protocols in ensuring excellent patient and graft survival rates. Our postulate was tested in a prospective study of 52 consecutive recipients of cadaver renal allografts (44 first, 5 second, and 3 third grafts) utilizing nifedipine as the first line calcium antagonist. Nifedipine was selected over verapamil or diltiazem due to its lack of interference with the metabolism of CsA. Some of the significant outcomes of our prospective trial were (A) a cumulative patient survival rate of 98.1% for the 52 recipients at 18 months posttransplantation; (B) a cumulative allograft survival rate of 92.1% for the 52 consecutive cadaver renal allografts at 18 months; (C) a cumulative allograft survival rate of 100% at 18 months for the 24 of 52 renal allografts without delayed graft function following transplantation; and (D) a cumulative allograft survival rate of 86% at 18 months for the 28 of 52 renal allografts with delayed graft function. Of the 4 of 52 who lost their grafts, 2 grafts were removed following discontinuation of immunosuppressive therapy while the remaining 2 had primary nonfunction; and (E) the lack of a requirement for monoclonal or polyclonal antibodies for the treatment of acute rejection episodes in this patient population. These gratifying results compare very favorably with (A) recent reports of the effects of long-term diltiazem therapy and of verapamil used in conjunction with an induction protocol that included Minnesota antilymphocyte globulin in recipients of cadaver renal allografts, and (B) the clinical outcome in many institutions with OKT3/ATG/ALG induction protocols. Whereas the mechanisms involved in the excellent clinical outcome found with the calcium antagonist remain undefined, our results strongly argue for a prospective, randomized and controlled study in which a calcium antagonist supplemented immunosuppressive regimen is compared with antibody-based induction protocols. PMID- 8497874 TI - Stability of renal allograft glomerular filtration rate associated with long-term use of cyclosporine A. AB - Renal allograft glomerular filtration rate (GFR) was measured at 4-month intervals for up to 1 year in 43 CsA-treated patients using x-ray fluorescence determination of plasma iohexol clearance. Study patients were divided into cohorts based on time (years) after transplantation at study entry (0-1; 1-2; 2 3; and > 3 years) and entry GFR levels (20-29; 30-39; 40-49; and > or = 50 ml/min/1.73 m2). GFR at study entry was 42 +/- 2 and was comparable in CAD (n = 31) versus LRD (n = 12) allografts (42 +/- 2 and 44 +/- 4 ml/min/1.73 m2, respectively). Range of entry GFR levels was similar in each of the "time at entry" cohorts defined above. Serum creatinine concentrations of 1.5-2.5 mg% were associated with GFR levels of 20-60 ml/min/1.73 m2. Serial GFR levels obtained at 4-month intervals for 1 year (n = 34 patients) were not consistent with a pattern of progressively declining GFR occurring as a function of either time after transplantation or absolute GFR level at study entry (intraindividual coefficient of variation 10.3 +/- 1.0%). Patients in the lower quartile of "entry GFR" levels (< 34 ml/min/1.73 m2) were more likely than their counterparts to have had a history of acute rejection. Results are consistent with retrospective population studies of aggregate serum creatinine levels, indicating that long-term CsA use is not uniformly associated with accelerated loss of renal allograft function consequent to a progressive, toxic nephropathy. The data also suggest that neither absolute GFR level nor time after transplantation represent indications for routine dose reduction or conversion to AZA. PMID- 8497875 TI - OKT3 for primary therapy of the first rejection episode in kidney transplants. AB - The improvement in one-year graft survival has allowed transplant centers to focus on long-term graft survival. A study of 665 primary cadaveric kidney transplants from a single center treated with cyclosporine demonstrated that patients did not develop chronic rejection if there was not an episode of acute rejection. This study is a retrospective review of 314 consecutive kidney transplants from a single center to determine if early, aggressive treatment of the first episode of acute rejection will improve graft survival without increasing recipient morbidity. The course of 314 consecutive kidney transplants performed during a 27-month period (245 CAD and 68 living-related) was studied. Demographic characteristics were equivalent between the two groups, and all patients received sequential quadruple immunosuppression using ALG and CsA. Patient and graft survivals at 2 years were 89.7% and 84%, respectively. At least one rejection episode occurred in 41% of the patients, one-half within 30 days of transplant. Rejection episodes were treated by oral prednisone taper, primary ALG or OKT3, or "rescue" therapy with ALG or OKT3. Graft survival in the 52 recipients treated with OKT3 for primary treatment of first rejection episode was 20% better than the 50 patients treated with PRED (P = 0.0847). Comparing the 39 recipients of primary CAD kidneys treated with primary OKT3 vs. 38 treated with PRED demonstrated a 32% improvement in 2-year graft survival (P = 0.033). There was no increase in second rejection episodes in patients treated with OKT3. Renal function was equivalent in patients with rejection regardless of type of antirejection therapy used. Of patients treated for rejection, 22% had symptomatic CMV infections, which were divided equally between the two groups. Eighty-two patients received a single course of OKT3, 28 received two courses, and 2 patients received OKT3 three times. Only two patients developed antimurine antibodies that required abandoning OKT3 for the treatment of rejection. This study clearly demonstrates that the early use of OKT3 as primary treatment of rejection results in significant improvement of 2-year graft survival in recipients of first CAD kidney transplants. There is no increase in episodes in CMV in patients treated with OKT3 as primary therapy and no increase in patient mortality. Early use of OKT3 does not prevent or decrease incidence of subsequent rejection episodes. Renal function in surviving grafts is not improved in patients treated with OKT3 vs. PRED.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8497876 TI - The beneficial effects of steroid withdrawal on blood pressure and lipid profile in children posttransplantation in the cyclosporine era. AB - Steroid therapy posttransplantation has been correlated with hyperlipidemia and hypertension. With improved graft survivals in the cyclosporine (CsA) era, post tx hyperlipidemia and hypertension may place children at high risk for early atherosclerosis. Presently there are no large studies assessing the metabolic effects of steroid withdrawal in tx children. Thus, we report on the effect of prednisone withdrawal on blood pressure, weight, and serum lipid levels in children post-tx maintained on CsA alone. Pred taper is attempted in patients on CsA (6-7 mg/kg/day) with stable graft function and is extended over a 6-month period. Once a rejection is diagnosed pred is restarted and no future attempts to withdraw are made. BP, weight, and overnight fasting serum cholesterol (Schol) levels were measured 1 month prior to complete withdrawal (A), and after 6 months without pred (B). In patients requiring the restart of pred, subsequent measurements were obtained 6 months later (C). Of 74 tx children, 7 had primary nonfunction. Pred was successfully withdrawn in 49% (33) of the remaining 67. Of these patients, 42% (14/33) are still maintained off pred with stable renal function for a mean duration of 58.5 months (range 8-99 months). Nineteen patients had to be restarted on pred secondary to rejection between 7-36 months after withdrawal. Three of the patients subsequently lost their grafts to further rejection episodes. Univariate and multivariate analysis failed to identify clinical predictors of successful steroid withdrawal. The Schol at B, 171 +/- 5.4 mg/dl (mean +/- SEM) was lower (P < .001) than at A (249 +/- 10 mg/dl) or C (257 +/- 20 mg/dl). The systolic BP at B (108 +/- 2.8 mmHg) and diastolic BP at B (68 +/- 2.6 mmHg) were also lower (P < .001) than at A (122 +/- 3.2, 76 +/- 2.7 mmHg) or C (130 +/- 5, 80 +/- 3.2 mmHg), respectively. No difference in weight was noted. Lipid profile (total chol, triglyceride, HDL, VLDL, LDL) was measured in 10/14 patients off pred (mean age at sample 16.25 years) and was compared with 13 patients on pred (mean 15.5 years). Both the total chol (176 +/- 9.2, 265 +/- 8.3 mg/dl) and LDL (109 +/- 10, 167 +/- 9.2 mg/dl) were higher (P < .001) in the group on pred. Based on our findings of increased LDL and total chol, children on long-term pred therapy post-tx may be at increased risk for atherosclerotic disease. PMID- 8497877 TI - Influence of the pretransplant hematocrit level on early graft function in primary cadaveric renal transplantation. AB - Although use of human recombinant erythropoietin has alleviated symptoms of anemia in renal failure, effects of increased hematocrit (HCT) on early post transplant renal function are unknown. Of 244 consecutive primary cadaveric kidney recipients transplanted over 74 months, 43% had HCT > or = 30% and 57% had HCT < 30% at transplantation. The incidence of delayed graft function (DGF) was greater in recipients with HCT > or = 30% (61%) than in recipients with HCT < 30% (33%; P = 0.0001). Ten percent of recipients with HCT > or = 30% experienced primary nonfunction (PNF) of the allograft (P = 0.0001). No recipient with HCT < 30% had PNF. Absolute rises in HCT over the 3 months preceding transplantation were greatest in those with PNF (2.5 +/- 2.4) followed by those with DGF (2.0 +/- 3.1) and immediate graft function (IGF) (0.2 +/- 5.2; P = 0.0328). Logistic regression analysis identified HCT > or = 30% (P = 0.0014), cold storage > or = 24 hr (P = 0.0006) and rising HCT (P = 0.0090) as independent predictors of DGF with relative risks of 3.1-, 3.3-, and 2.7-fold, respectively. Recipients with rising pretransplant HCTs who underwent dialytic fluid removal within 24 hr before transplantation had DGF with greater frequency (67%) than nondialyzed recipients with rising HCTs (45%). Primary cadaveric kidney recipients with HCT > or = 30% at transplantation have significantly greater risk for DGF and PNF. Rising pretransplant HCT levels may predispose recipients to DGF; this risk may be heightened in those undergoing hemodialysis shortly before transplantation. PMID- 8497878 TI - Potentiation of cyclosporine nephrotoxicity by nafcillin in lung transplant recipients. AB - The interaction between nafcillin and cyclosporine was examined in lung transplant recipients receiving cyclosporine-based immunosuppression. Nine recipients received nafcillin for one week posttransplant and 10 recipients did not receive nafcillin. Age, sex, pretransplant renal function, type of transplant procedure, use of cardiopulmonary bypass, and initial cyclosporine dose were not significantly different between groups. The degree of renal dysfunction during the early postoperative period was significantly greater in the lung recipients receiving nafcillin. Although cyclosporine doses were significantly higher in the nafcillin group, this was not reflected by differences in cyclosporine levels. No difference in survival or incidence of allograft rejection was seen--however, the incidence of viral infection was significantly higher in the patients who received nafcillin. Based on our findings the use of an alternative antibiotic for antistaphylococcal prophylaxis in transplant recipients receiving cyclosporine is recommended. PMID- 8497879 TI - Primary diagnosis predicts prognosis of lung transplant candidates. AB - Optimal timing for consideration of lung transplantation remains unknown. This study examined survival in patients with end-stage lung disease awaiting transplantation. Primary disease group and relevant indicators were evaluated. Ninety-three patients who met selection criteria for lung transplantation were included in this retrospective review. Of this total, 31% underwent transplantation, 38% remain waiting, and 31% died. Results demonstrate that the six-month actuarial survival rate was 89% for Eisenmenger's syndrome, 81% for emphysema, 74% for cystic fibrosis, 60% for primary pulmonary hypertension, and 38% for interstitial lung disease. Parameters found to be significant included a higher mean right atrial pressure in primary pulmonary hypertension patients who died awaiting transplantation, and lower forced expiratory volume in one second and forced vital capacity measurements in cystic fibrosis patients who died awaiting transplantation. We conclude that primary disease significantly affects survival in candidates awaiting transplantation. Reliable indicators predictive of survival are not available. Earlier referral for consideration of lung transplantation is recommended. PMID- 8497880 TI - Right ventricular assessment in patients presenting for lung transplantation. AB - Chronic pulmonary disease is associated with varying degrees of cardiac dysfunction. Because of the potentially predominant effect of severe lung disease on right ventricular (RV) size and function, a reliable method to assess RV mechanics before and after lung transplantation may provide information of long term significance and/or prognosis. Conventional invasive and non-invasive imaging methods have a number of limitations in evaluating RV function. Ultrafast computed tomographic (ultrafast CT) scanning has been shown to provide quantitative assessment of RV and left ventricular (LV) function in individuals with and without cardiac disease. Twenty-two patients presenting during evaluation for possible lung transplantation with end-stage pulmonary disease formed the basis of this study. There were 14 patients with chronic obstructive pulmonary disease and 8 with pulmonary fibrosis. Conventional transthoracic echocardiography and ultrafast CT were used for the assessment of RV and LV function. All patients had invasive assessment of right-sided hemodynamics and pulmonary function studies performed within 7-10 days of cardiac imaging. A qualitative assessment of RV size or function was possible in all but two patients by echocardiogram, but in 45%, the echocardiographic examination was described as suboptimal. In contrast, a quantitative assessment of ventricular volumes and systolic function was obtained in all patients by ultrafast CT. Pulmonary function parameters or hemodynamic measurements obtained during cardiac catheterization did not correlate with any assessment of RV function. We concluded that (1) ultrafast CT provides measurement of the RV and LV cavity dimension and systolic function; (2) invasive right-sided hemodynamics or pulmonary function studies do not predict RV function; and (3) echocardiography does not uniformly provide assessment of RV function in patients with chronic pulmonary disease. PMID- 8497881 TI - Tissue plasminogen activator in human cardiac allografts. AB - The activation of hemostasis and fibrinolysis frequently is observed in allografted organs. Plasminogen is activated by urokinase and tissue plasminogen activator (tPA). We have studied human hearts before and after transplantation to determine if fibrin deposition within the microcirculation is associated with a depletion of myocardial tPA, and if such depletion of tPA is associated with decreased fibrinolysis. We found that tPA in pretransplanted hearts and in biopsies from hearts of most patients with a stable clinical course is confined to arterial and arteriolar smooth muscle cells. The depletion of smooth muscle cell reactivity was associated with microvascular fibrin deposition in unstable allografts, and the appearance of endothelial cell tPA reactivity heralded a bad prognosis. Successful medical management was signaled by a loss of endothelial tPA reactivity and a return of tPA reactivity in arterial and arteriolar smooth muscle cells. These findings indicate a central role for tPA in maintaining the integrity of the microcirculation in transplanted human hearts. PMID- 8497882 TI - Prevention of adverse clinical outcome by monitoring of cardiac transplant patients for murine monoclonal CD3 antibody (OKT3) sensitization. AB - We have previously reported that patients sensitized to murine monoclonal CD3 antibody (OKT3) and maintained on such therapy for induction of immunosuppression have a high mortality and/or allograft loss. In this follow-up study, we retrospectively reviewed all patients routinely and serially monitored by flow cytometry for plasma levels of OKT3 during a 21-month period beginning 1/90. A total of 112 patients were monitored during this period. We retrospectively tabulated the incidence of OKT3 sensitization, rejection pattern and impact on survival of withdrawal of OKT3 at the time of sensitization as compared with the previous study in which withdrawal was not done. Nine patients were excluded from analysis because of withdrawal for reasons other than sensitization: cytokine encephalopathy, infection, postoperative complications, or severe rejection. Twelve patients had OKT3 therapy aborted because of failure to achieve steady state OKT3 levels or because of decline in levels while on therapy. These patients were thus defined as being sensitized to OKT3. No patient was aborted because of return of CD3 cells in the blood. Only one of the 12 patients sensitized to OKT3 died. Of 91 patients with steady-state OKT3 levels, 6 had high plasma levels (> 1000 ng/ml) and 6 had low plasma levels (< 500 ng/ml). None of these patients had OKT3 therapy aborted and all are alive. Twelve of these 91 patients had successful retreatment with OKT3 for refractory rejection, indicating that absence of sensitization on induction predicts safety of retreatment with OKT3. We also examined the frequency of associated human antimouse antibody (HAMA) production using the blocking assay modified from Jaffers and Mayes. Only the sensitized patients exhibited a significant association with HAMA production (6/7 tested, P = 0.05) Classification of the rejection pattern of the sensitized patients confirmed our previous results: eight of 12 had vascular rejection and 4/12 had mixed rejection. These patterns were prospectively determined. We conclude that serial monitoring of patients for plasma levels of OKT3 is an effective strategy to prevent adverse outcomes of induction with this agent. PMID- 8497883 TI - The lack of long-term detrimental effects on liver allografts caused by donor specific anti-HLA antibodies. AB - Recent reports indicate a higher incidence of both acute and chronic liver allograft rejection when, at the time of transplantation, the recipients serum contains donor-specific anti-HLA antibodies. From 9/89 to 5/91, 133 liver allografts were performed at our institution. Thirteen liver recipients had donor specific IgG anti-HLA antibodies (complement-fixing) at the time of transplantation. In eleven patients, antibodies reacted to donor class I antigens while in 1 patient the donor-specific antibody had class II reactivity. Twelve patients have been followed for a minimum of 12 months (median 18 months, range 28-12 months). No hyperacute rejection was seen in any of the cases and four patients had acute rejections. Thus far only one of the twelve patients has biopsy evidence suggestive of chronic liver injury. The remaining have normal liver enzymes and bilirubin. Three of these twelve patients died (one from a myocardial infarction and the others from sepsis) accounting for a one-year graft survival of 75%. There was no significant statistical difference in the one-year graft survival in those recipients without donor-specific antibodies (i.e., 80.5%). In eight of the twelve patients, pretransplant preformed antibody level (PRA) was > 50%. In six of the thirteen patients donor-specific antibody was present at dilutions greater than 1:64. As previously reported, the donor specific antibody disappeared from the serum posttransplant within hours and did not reappear. In vitro studies demonstrated no factor in portal or hepatic artery blood that could inhibit rabbit complement mediated lysis of anti-HLA antibodies. We conclude that it is not a contraindication to do liver transplants in the presence of donor-specific anti-HLA antibodies. PMID- 8497884 TI - Nonoperative management of biliary leaks after orthotopic liver transplantation. AB - Specific therapy should be instituted expeditiously once the diagnosis of a biliary leak has been made in patients who have undergone orthotopic liver transplantation. Controversy exists over whether to use nonoperative or operative management. The results of 325 consecutive orthotopic liver transplants in 297 adult and pediatric recipients were reviewed. The biliary tract was reconstructed using a choledochocholedochostomy anastomosis (254/325 or 78%) or a Roux-en-Y choledochojejunostomy anastomosis (71/325 or 22%). The incidence of biliary leaks was 23% (74/325). Overall, only 3% (10/325) of the orthotopic liver transplant recipients required operative repair of a biliary leak. Biliary leaks occurring in patients with Roux-en-Y choledochojejunostomy anastomoses (9/71 or 13%) commonly required operative repair (6/9 or 67%), whereas leaks that occurred in patients with choledochocholedochostomy anastomoses (65/254 or 26%) seldom required operative repair (4/65 or 6%). All choledochojejunostomy leaks occurred at the anastomosis, whereas choledochocholedochostomy leaks occurred either at the anastomosis (17/254 or 7%) or the T-tube insertion site (45/254 or 18%). Our study confirms that in centers with proficient endoscopic and interventional radiologic support, resolution of biliary leaks in orthotopic liver transplant patients can be achieved with nonoperative management. PMID- 8497885 TI - Causes of late graft loss after liver transplantation. AB - The causes of graft loss in liver transplant recipients with a graft functioning for more than 1 year post-transplant were analyzed. Of 500 liver transplants in 434 patients, 362 grafts were functioning for more than 1 year. After 1 year, 42 grafts were later lost (11.6%). Thirty-three grafts were lost by death and 9 retransplants were done with 8 patients. Of the grafts lost by death, 12 had no evidence of dysfunction. The actuarial 2- and 5-year graft survival in liver transplantation recipients with functioning grafts for more than 1 year was 91 and 83%, respectively. The graft loss rate was 3.4 times higher during the 2nd year post-transplant than during 2-5 years post-transplant. The most common causes of graft loss were chronic rejection (26.2%), recurrent hepatitis (23.8%), arterial thrombosis/stenosis (11.9%) and recurrent malignancy (9.5%). No graft was lost from acute rejection. There was no difference in timing of the graft lost between the different causes. The pretransplant diagnosis of hepatitis B, chronic rejection, and malignancy was associated with the highest frequency of late graft lost. In conclusion, long-term graft survival is good after liver transplantation in patients with a functioning graft for more than 1 year. The main causes of graft loss were chronic rejection and recurrent hepatitis. Prevention and treatment for these conditions may further improve the results after liver transplantation. PMID- 8497886 TI - Retransplantation of the liver--a seven-year experience. AB - Three hundred and four patients underwent 362 liver transplants between July 1984 and April 1992. Fifty-eight retransplants were performed in 44 patients (14.5%). Thirty-four patients underwent two (77.3%), seven patients three (15.9%), two patients four (4.5%), and one patient five (2.3%) transplants. Poor function accounted for 23 retransplants (6.4%), technical problems for 19 retransplants (5.2%), and rejection for 15 retransplants (4.1%). One-month patient survivals after retransplantation for poor function, technical problems, or rejection were similar (79.0%, 73.4%, and 80.0%, respectively). No difference in retransplantation rates were seen between adults and children receiving whole liver transplants (WLT) (11.6% versus 19.1%). However, retransplantation for poor function was more common in pediatric recipients receiving reduced-size liver transplants (RLT) (20.0% versus 0.0%, P < 0.01), while retransplantation for hepatic artery thrombosis (HAT) was more common in pediatric recipients receiving WLT (16.7% versus 2.8%, P < 0.05). The presence of multiorgan system failure of greater than four was associated with a high mortality (90%), whereas patients undergoing emergent retransplantation who had less than four systems fail had a survival of 73.9% and patients who underwent elective retransplantation had a survival rate of 81.8%. Length of stay and cost of liver transplantation was higher in patients undergoing retransplantation when compared with primary transplants (29.7 +/- 14.9 days versus 58.4 +/- 38.9 days and $122,358 +/- 59,782 versus $289,302 +/- 126,907, P < 0.01). The overall actuarial one-year patient survival in primary transplants was 86.6% and in retransplants 74.8%, and at five years these were 71.4% versus 62.5%, respectively (P < 0.05). Our results support continued retransplantation of the liver unless the patient's medical condition dictates otherwise. PMID- 8497887 TI - Liver biopsy. Its safety and complications as seen at a liver transplant center. AB - Liver biopsy is a frequently utilized diagnostic tool at a liver transplant center. It is occasionally utilized prior to OLTx to determine whether or not a potential recipient either has tumor or a disease process that has some chance of spontaneous recovery without OLTx. Following OLTx, it is often utilized to determine the need to alter a recipient's immunosuppression regimen or gauge the response to a recent change in immunosuppression. At the University of Pittsburgh Medical Center, adult liver transplant patients have been biopsied using 3 different techniques based upon the physician's (Tru-cut needle) or surgeon's (suction needle) personal choice and whether or not it has been the intent of the biopsy to obtain tissue from a focal lesion within a liver. In the latter cases, ultrasound guidance and an automated biopsy needle are used. In the former, either a suction-type needle (Jamshidi) or a cutting needle (Tru-cut) has been used. During the period between January 1, 1989, and December 31, 1991, a total of 12,750 liver biopsies have been done on patients admitted to the adult transplant service at this institution. Of these, 8500 were performed with a suction needle, 4195 were performed using a cutting needle, and 55 were performed under ultrasound guidance using an automated cutting needle. A total of 26 major complications occurred--19 with the suction needle (0.22%); 6 with the cutting needle (0.14%), and 2 using ultrasound guidance and an automatic cutting needle (3.6%). Nine of these 26 complications required surgical intervention consisting of a thoracotomy or laparotomy; 4 required the insertion of a chest tube and two required hepatic artery embolization. Based upon these data obtained at a large transplant center, it can be concluded that, in general: (1) a liver biopsy can be done safely in liver transplant recipients; (2) an overall low rate of major complications occurs varying from 0.1 to 3.6% depending upon the type of needle and other circumstances relating to the biopsy procedure; (3) complications, when they occur, are morbid and often necessitate either additional surgical or interventional radiologic procedures. PMID- 8497888 TI - Recipient selection and evaluation for vascularized pancreas transplantation. AB - Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection. PMID- 8497889 TI - Promotion of rat cardiac allograft survival by intrathymic inoculation of donor splenocytes. AB - Donor-specific unresponsiveness to LEW heterotopic cardiac allografts was induced in WF rats following intrathymic inoculation of LEW splenocytes in conjunction with a single intraperitoneal dose of antilymphocyte serum. In contrast, LEW cardiac allografts were promptly rejected in WF recipients pretreated with an intravenous inoculation of donor splenocytes. Without transient immunosuppression with antilymphocyte serum neither intrathymic nor intravenous inoculation of splenocytes led to allograft survival. Substitution of antilymphocyte serum by a short course of cyclosporine did not permit allograft survival, suggesting that a T-cell-depleting regimen is crucial to tolerance induction by this protocol. The unresponsive state could be transferred to secondary syngeneic hosts by spleen cells from long-term recipients of intrathymic splenocytes and cardiac allografts but not by spleen cells from recipients of intrathymic splenocytes alone. This suggests that persistence of donor alloantigen from the graft is necessary for maintenance of the tolerant state. The unresponsive state after intrathymic inoculation of allogeneic splenocytes may be mediated through interaction of maturing host thymocytes with donor alloantigen. PMID- 8497890 TI - Effect of a short course of rapamycin, cyclosporin A, and donor-specific transfusion on rat cardiac allograft survival. AB - The interactions of rapamycin (Rapa), CsA, and donor-specific transfusion (DST) were examined in an ACI to Lewis rat heterotopic cardiac allograft model. Survival data were truncated at 175 days for the purpose of statistical comparisons. Vehicle (Veh)-treated animals rejected at a mean of 7.3 +/- 0.2 days. Treatment with a DST on the day before transplantation (d-1) resulted in a decreased survival of 5.5 +/- 0.3 days (P < 0.05). An 8-day course of low-dose CsA (d-1 to d6) in Veh-treated animals prolonged allograft survival to 10.3 +/- 0.5 days (P < 0.05). The addition of a DST d-1 to the Veh/CsA-treated animals resulted in a synergistic prolongation of survival to 45.7 +/- 12.5 days (P < 0.05). Rapa proved to be a potent immunosuppressive agent in this model, with an 8-day course of Rapa (d-1 to d6) at 0.5 mg/kg/day (R1) or 1.5 mg/kg/day (R2), resulting in mean allograft survivals of 24.2 +/- 5.0 and 67.3 +/- 20.9 days, respectively (P < 0.05 vs. Veh or Veh/CsA). Rapa demonstrated synergy with CsA by further prolonging allograft survival to 115.9 +/- 27.9 days (R1/CsA, P < 0.05 vs. Veh/CsA, R1) and 164.6 +/- 10.4 days (R2/CsA, P < 0.05 vs. Veh/CsA). The extended graft survival using a combination of Rapa and DST, compared to Rapa alone, did not prove to be statistically significant. When all three treatments were combined (Rapa/DST/CsA), no significant benefit to survival was seen over Veh/DST/CsA (45.7 +/- 12.5 days vs. R1/DST/CsA, 81.9 +/- 18.4 days; R2/DST/CsA, 98.5 +/- 21.3 days; P > 0.05). If Rapa was withheld until postoperative day 1 (Rapa, 1.5 mg/kg/day on d1 to d6/DST/CsA), enhancement of the DST/CsA effect was seen with a mean survival of 170.2 +/- 4.8 days (P < 0.05). This suggests that the timing of Rapa administration may significantly impact its interaction with DST/CsA treatment and merits further investigation. PMID- 8497891 TI - Oral, but not intravenous, alloantigen prevents accelerated allograft rejection by selective intragraft Th2 cell activation. AB - We studied the mechanisms by which oral or intravenous administration of allogeneic splenocytes prevents sensitization by skin allografts and development of accelerated rejection of subsequent cardiac allografts. LEW rats were sensitized with BN skin allografts 7 days prior to receiving heterotopic (LEW x BN)F1 vascularized cardiac allografts. While unsensitized cardiac allografts are rejected on days 6-8, control sensitized grafts were rejected within 24 to 48 hr. Oral administration of BN splenocytes during the sensitization phase (between skin and heart grafting) has been found to prevent accelerated allograft rejection and prolong cardiac allograft survival to 7 days. An alternative route of antigen exposure, specifically intravenous administration of BN splenocytes (50 x 10(6) daily for 5 days starting on the day of skin grafting), also prevented accelerated cardiac allograft rejection and prolonged allograft survival to 9 +/- 1 days (n = 5). Immunoperoxidase studies of cardiac allografts harvested 24-48 hr posttransplant showed that, when compared with sensitized controls, animals that received oral splenocytes had reduced deposition of IgG (end-point titer of 1/1000 vs. 1/4000), IgM (1/1000 vs. 1/16000), C3 (1/4000 vs. 1/16000), and fibrin (1/4000 vs. 1/16000). There was also decreased infiltration by macrophages (18 +/- 8 vs. 37 +/- 8 cells/HPF, P < 0.01), T cells (5 +/- 3 vs. 19 +/- 7, P < 0.01), and IL-2R+ T cells (5 +/- 3 vs. 15 +/- 4, P < 0.01), and a significant reduction in the numbers and extent of intragraft mononuclear cells stained with antibodies to IL-1, IL-2, IL-6, IL-8, IFN-gamma, and TNF-alpha. In contrast, these grafts showed markedly increased IL-4 staining (including most mononuclear and all endothelial cells), as compared with control grafts (< 20% of mononuclear cells and only focal endothelial staining). Immunoperoxidase studies of cardiac allografts harvested from rats receiving intravenous splenocytes also showed markedly reduced humoral deposits and cellular infiltrates, comparable to that found in the oral splenocytes-treated group, but showed significantly different cytokine expression. In particular, some intragraft mononuclear cell labeling for IFN-gamma remained, and IL-4 staining was not increased relative to control grafts. Attempts were then made to abrogate spleen cell-induced prolongation of cardiac allograft survival by daily injections of CD4 monoclonal antibody (BWH-4 mAb, 700 micrograms) from the time of cardiac transplantation, therapy previously shown unable to prolong cardiac survival in this model when commenced after skin graft-induced sensitization has occurred.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8497892 TI - 15 AU81, a prostacyclin analog, potentiates immunosuppression and mitigates renal injury due to cyclosporine. AB - 15 AU81, a synthetic prostacyclin analog, inhibits human mixed lymphocyte culture responses in a dose-dependent manner at concentrations within a range [0.1 to 10.0 micrograms/ml] similar to that of cyclosporine, methylprednisolone, antilymphocyte serum, and prostaglandin E1 and E2 analogs. Using the median effect analysis to dissect immunosuppressive interactions, 15 AU81 and cyclosporine were shown to produce synergistic effects on human peripheral blood lymphocyte activation upon phytohemagglutinin or anti-CD3 monoclonal antibody stimulation. In vivo, 15 AU81 potentiated the effect of cyclosporine to prolong the survival of rabbit renal allografts using concentrations of each agent that were individually ineffective. Furthermore, addition of 15 AU81 mitigated functional damage of rabbit kidneys due to high-dose cyclosporine therapy. These observations suggest that the addition of 15 AU81 may broaden the therapeutic window of cyclosporine by potentiating immunosuppression and mitigating nephrotoxic effects. PMID- 8497893 TI - Cyclosporine and rapamycin affect protein kinase C induction of the intracellular activation signal, activator of DNA replication. AB - Immunosuppressive agents may initiate their pharmacologic action by disrupting phosphorylation cascades critical to T lymphocyte intracellular signaling after alloantigen recognition. Activator of DNA Replication (ADR), a transduction signal sensitive to CsA as well as rapamycin (RAPA) immunosuppression, seemed a likely candidate for phosphoregulation. This communication reports the development of a cell-free assay wherein CsA and RAPA inhibit ADR induction by protein kinase C (PKC). ADR and PKC are inactive in the cytosol of resting cells. Endogenous PKC activity in quiescent lymphocytes was triggered with the tumor promoter PMA, leading to the appearance of ADR, an event subsequently quantitated by the ability of ADR to trigger [3H]thymidine triphosphate incorporation into isolated nuclei. After PKC induction, ADR activity is increased (890 +/- 120 vs. 3910 +/- 345 cpm, P < 0.001). In the presence of the PKC inhibitor H7, ADR activity fails to increase (100 +/- 50 vs. 3910 +/- 345 cpm, P < 0.001). The high levels of ADR found in PHA-stimulated cells is marginally affected by in situ PKC induction, although the sustained impact of H7 throughout the cell cycle suggests that ADR is constantly being phosphorylated. Titration of CsA or RAPA into the cell-free system inhibited ADR induction in a dose-dependent fashion. The utility of ADR induction as a marker for immunosuppression was investigated by comparing ADR inducibility in resting cells that had been preloaded with CsA or RAPA with the proliferative index of cells cultivated with CsA or RAPA. ADR induction directly correlated with CsA or RAPA proliferative inhibition. The results suggested that ADR is a constituent of the PKC phosphoregulatory cascade essential for cell cycle progression. The correlation between cell-free ADR inducibility and proliferative inhibition by CsA or RAPA suggest that this procedure may be useful for in vitro prediction of allografted patient immunologic response. PMID- 8497894 TI - Different patterns of sensitization following renal allograft rejection in an inbred rat strain combination. AB - Exposure to MHC antigens by kidney transplantation can result in long-term sensitization or tolerance. In order to characterize immune responses to an acutely rejected renal allograft, ACI (RT1a) kidneys were transplanted into untreated male PVG (RT1c) recipients and allowed to reject while one native kidney remained in situ for host survival. Two distinct patterns of recipient sensitization were found based on early IgM responses to RT1.Aa following rejection, with "weakly sensitized" and "strongly sensitized" groups comprising approximately 40% and 60%, respectively, of the recipients. Serum taken from strongly versus weakly sensitized animals at the time of peak IgM responses (7 days post-transplantation) showed greater ability to block binding of anti-RT1.Aa mAb (R2/15S, R2/10P, or YR1/100) to PVG.1A (RT1a class I and II on a PVG background) lymph node target cells. Sera obtained from strongly sensitized recipients during peak IgG responses (4 weeks after kidney transplantation) demonstrated significantly higher IgG2a and IgG2b alloantibody levels than weakly sensitized rats at all serum dilutions (1:4-1:1024). Allografts harvested 10 days after transplantation from strongly sensitized recipients (strong R2/10P-blocking serum, n = 9) had a vascular pattern of rejection characterized primarily by extensive vascular endothelial damage, glomerular and cortical necrosis, and gross infarction of the graft. In contrast, grafts harvested from weakly sensitized recipients at 10 days, 21 days, or > 6 months (n = 6, 10, and 6, respectively) posttransplantation showed a significantly different pattern of rejection, with moderate interstitial lymphocytic infiltrates but substantial preservation of the general kidney architecture. When challenged 13 weeks posttransplantation, strongly sensitized animals rejected RT1.Aa class I disparate PVG.R1 skin grafts in an accelerated fashion, whereas such grafts survived indefinitely on weakly sensitized recipients. These findings indicate that two patterns of renal allograft rejection can occur between a fixed strain disparity, one of which results in long-term sensitization and the other with partial tolerance to donor class I MHC antigens, as evidenced by (1) decreased production of IgM, IgG2a and IgG2b isotype alloantibody to donor class I MHC antigen epitopes after kidney rejection and (2) acceptance of donor class I disparate skin grafts. PMID- 8497895 TI - The effect of bursectomy on natural xenoreactive antibodies and vascularized rat cardiac xenograft rejection in the chicken. AB - The clinical application of xenotransplantation between distantly related species is currently prevented by the occurrence of hyperacute rejection (HAR). Controversy exists over the importance of natural xenoreactive antibody (NAb) mediated activation of the classical complement pathway vs. direct activation of the alternative C pathway in this process. In order to evaluate HAR of xenografts (Xgs) in the absence of NAb, this study utilized K strain leghorn chickens that were bursectomized (Bx) on day 17 in ovo (n = 18) to prevent B cell development and production of NAb. Aged-matched untreated siblings served as controls (n = 13). Based on pretransplant antibody levels, the Bx chickens were divided into two groups: totally Bx (Total Bx, n = 9) and partially Bx (Part Bx, n = 9). Chickens then underwent heterotopic cardiac xenotransplantation using PVG rats as donors, where the Xg was connected to the circulation of the chicken recipient utilizing cannulae. For the control group, Xg survival was 28 +/- 3 min (mean +/- SEM), while Part Bx prolonged survival to 80 +/- 15 min. Total Bx extended rat Xg survival to 102 +/- 11 min, with 5 of 9 Xgs functioning well at the time of termination of the study (90-120 min). Three chickens in the Total Bx group with rat cardiac Xgs that were functioning at 120 min were given a 1 ml i.v. injection of heat inactivated control chicken serum. This led to loss of Xg function within 10 min, confirming the important role for NAb in HAR in this species combination. Histologic examination of the Xgs following perfusion revealed significant arterial endothelial injury in the control and Part Bx groups but not in the Total Bx group. Conversely, Xgs from the Total Bx group showed marked venous congestion, which was not seen in the other two groups. This study demonstrates that: (1) Bx effectively eliminates NAb; (2) Xg survival is significantly prolonged in the absence of NAb in this rat-to-chicken xenogeneic combination; (3) the presence of NAb is associated with arterial endothelial injury; and (4) in the absence of NAb, marked venous congestion and injury occurs, which is possibly mediated by alternative C pathway activation or other humoral mechanisms. PMID- 8497896 TI - Characterization of human anti-porcine "natural antibodies" recovered from ex vivo perfused hearts--predominance of IgM and IgG2. AB - Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved in hyperacute rejection of pig heart xenografts were identified and characterized using an ex vivo model in which pig hearts were perfused with whole blood from individual human or pig donors. This ex vivo perfusion model allows for the continuous monitoring of physiologic parameters of cardiac function as well as sequential sampling of tissue and blood. Pig hearts perfused with allogeneic pig blood maintained normal function for at least 4 hr, whereas those perfused with xenogeneic AB+ human blood never achieved normal function and rejected completely after 30 min. In three separate experiments involving different human blood donors and pig hearts, sequential samples of perfused blood revealed a progressive depletion of anti-porcine NAb. Samples of all three rejected cardiac xenografts were homogenized, and the specifically bound human anti-porcine antibodies were eluted with citric acid. The eluted antibodies were enriched approximately 50-120-fold for anti-porcine reactivity compared with serum from the corresponding donor. Eluates contained NAb of predominantly IgM and IgG2 isotypes. Immunofluorescence histology confirmed the deposition of IgM and IgG2 but not other IgG subclasses in the rejected pig hearts. Since IgG2 utilized predominantly in response to bacterial polysaccharide antigens, our findings are consistent with the possibility that some NAb arise via crossreactivity with microbial antigens and are predominantly directed against carbohydrate rather than protein antigens. PMID- 8497897 TI - IL-2 and IL-5 gene expression in response to alloantigen in liver allograft recipients and in vitro. AB - IL-2 and IL-5 gene expression in response to alloantigen was studied in liver allograft recipients and in an in vitro system. Seventy-seven sequential liver allograft biopsies from 22 patients were analyzed for IL-2 and IL-5 mRNA by polymerase chain reaction and Southern blot hybridization. Message for IL-5 was present in 74% of allografts with rejection, 46% of allografts with resolving rejection, and 33% of allografts with no evidence of rejection. The frequency of IL-5 transcripts in rejecting allografts was significantly different than the frequency of IL-5 transcripts in grafts without evidence of rejection (P = 0.003). Message for IL-2 was detected in 29% of rejecting allografts, 18% of allografts without evidence of rejection, and 43% of allografts with resolving rejection. There was no significant association between IL-2 gene expression and the histopathological status of the allograft. Interestingly, 9 of 15 biopsies that contained IL-2 message in the no rejection and resolving rejection categories went on to display rejection shortly thereafter. IL-2 and IL-5 gene expression rarely occurred simultaneously within allografts. An in vitro system consisting of irradiated, allogeneic stimulator cells and normal peripheral blood mononuclear cells as responders was established to further investigate alloantigen-driven IL-2 and IL-5 production. Both IL-2 and IL-5 were produced in response to alloantigen as determined by specific bioassays. Maximal levels of IL 5 activity in culture supernatants generally followed maximal IL-2 levels by 24 hr, but both IL-2 and IL-5 production were dramatically inhibited by CsA. Analysis of cytokine gene expression revealed that IL-2 transcription peaked within the initial 24 hr of culture, whereas IL-5 transcription was maximal at 120 hr of culture. The expression of a CTL-specific serine esterase gene was similar to IL-5 in that it was maximal during the latter phases of the culture period. Thus, both human IL-2 and IL-5 are produced in response to alloantigen and are inhibitable by CsA. These data suggest that IL-2 and IL-5 may participate in cellular pathways of tissue damage within the rejecting allograft. PMID- 8497898 TI - Hypertension with combined pancreas-kidney transplantation in patients with diabetic nephropathy. PMID- 8497899 TI - The effect of hepatitis B in a dialysis transplant program. PMID- 8497900 TI - T cell subset analysis by flow cytometry during MALG induction for pediatric renal transplantation. PMID- 8497901 TI - Percutaneous treatment of ureteral strictures after renal transplantation. PMID- 8497902 TI - Evaluation of ticlopidine, a novel inhibitor of platelet aggregation, in heart transplant recipients. PMID- 8497903 TI - The efficacy of LFA-1 and VLA-4 antibody treatment in rat vascularized cardiac allograft rejection. PMID- 8497904 TI - A comparison among the effects of donor-specific whole blood, bone marrow, and spleen leukocytes on allograft survival when combined with cyclosporine. PMID- 8497905 TI - Combination chemotherapy for posttransplant cyclosporine-related non-Hodgkin's lymphoma. PMID- 8497906 TI - Proceedings of the 11th annual meeting of the American Society of Transplant Physicians. Chicago, Illinois, May 1992. PMID- 8497907 TI - Production of less chronic nephrotoxicity by cyclosporine G than cyclosporine A in a low-salt rat model. AB - Chronic tubulointerstitial nephropathy during long-term cyclosporine A (CsA) use has led to a search for equally effective but safer analogues. In this study we evaluated one of these analogues, cyclosporine G (CsG), in a rat model of chronic cyclosporine nephrotoxicity. CsG has immunosuppressive effects equivalent to CsA when dosed on a weight basis. Pair-fed Sprague-Dawley rats kept on a low-salt rice diet were given CsA 15 mg/kg, CsG 15 mg/kg, CsG 25 mg/kg, or vehicle subcutaneously. After 21 days, CsA animals had a lower glomerular filtration rate, measured by inulin clearance (0.16 +/- 0.04 ml/min/100 g) and higher serum creatinine (0.94 +/- 0.06 mg/dl) than CsG 15 mg/kg (GFR: 0.41 +/- 0.10 ml/min/100 g and serum creatinine: 0.68 +/- 0.09 mg/dl), CsG 25 mg/kg (GFR: 0.39 +/- 0.16 ml/min/100 g) or control rats (GFR: 0.62 +/- 0.06 ml/min/100 g; serum creatinine: 0.56 +/- 0.03 mg/dl), respectively (P < 0.05). The CsA group had considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), whereas both groups of CsG animals had more limited changes. Despite the same or larger doses of CsG on a weight basis, cyclosporine blood levels were significantly lower in CsG than CsA rats. We conclude that CsG, an analogue of cyclosporine with immunosuppressive activity equivalent to that of CsA, produced less nephrotoxicity in a model of chronic renal injury in rats, using both functional and structural parameters. PMID- 8497908 TI - The participation of tumor necrosis factor in the pathogenesis of lung allograft rejection in the rat. AB - Tumor necrosis factor alpha and beta are polypeptide cytokines with a wide range of metabolic, immunologic, and inflammatory activities. TNF is known to participate in immune mediated injury of native lungs, but a role for TNF in mediating lung allograft rejection (AR) has not been established. In experiments reported here, we assessed the role of TNF in mediating lung AR in a rat model of lung transplantation (BN-->Lew) (RT1n-->RT1l). This model shows florid AR with all grafts completely destroyed by day 6 posttransplant. Graft pathology is characterized by massive lymphocytic infiltrates and hemorrhagic necrosis. Initially, 5 lung allograft recipients in each group were sacrificed on days 1 to 6 posttransplant. Allografts were removed, mRNA isolated, and Northern blotting or RT-PCR performed with blots probed with cDNAs or oligos specific for rat TNF alpha cyclophylin and gamma-actin. Data were compared with syngeneic transplants (Lew-->Lew) and with normal controls. In addition, frozen lung allograft tissue was examined by indirect immunofluorescence, using antibodies specific for TNF. TNF-alpha mRNA levels were detectable on day 2 posttransplant, and peaked on days 6-7 posttransplant. IF studies showed TNF protein expression in mononuclear cells of rejecting allografts on day 3, peaking on day 6. Both TNF-alpha mRNA and protein levels correlated with maximal AR and hemorrhagic necrosis of grafts. Minimal TNF-alpha mRNA or protein was detected in syngeneic grafts or in contralateral native lungs. We then examined the ability of a rabbit polyclonal anti-TNF-alpha (7000 U/day) and anti-TNF-beta (5000 U/day) with 30% crossreactivity with rat TNF to modify the AR response. For each group, 4-5 left lung transplants were performed as described, and animals treated with anti-TNF alpha, anti-TNF-beta, (anti-TNF-alpha+anti-TNF-beta) or with preimmune rabbit sera. All animals were sacrificed on day 6 posttransplant. Several pathological categories of inflammation were examined and scored (0-4), with a score of 0 = 0% involvement; 1 = 1-25% involvement; 2 = 26-50% involvement; 3 = 51-75% involvement; and 4 = 76-100% involvement. The mean and SD scores were obtained for all animals in the treatment categories mentioned above, and compared with preimmune-treated controls. Briefly, no differences in perivascular, peribronchial, or peribronchiolar cell infiltrates or edema were seen in treatment groups compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8497909 TI - Effects of Carolina rinse and adenosine rinse on microvascular perfusion and intrahepatic leukocyte-endothelium interaction after liver transplantation in the rat. AB - Flushing hepatic grafts immediately before revascularization with a specially designed rinse solution such as "Carolina rinse" has been reported to improve survival after liver transplantation in the rat. This study investigated the influence of Carolina rinse and adenosine rinse on early graft function, microcirculation, and leukocyte (WBC)-endothelial cell interaction of arterialized syngeneic orthotopic liver transplants in Lewis rats. Livers were preserved for 24 hr in University of Wisconsin solution and flushed immediately before reperfusion with either Ringer's lactate (group A: n = 7), Ringer's lactate + 0.2 mmol/liter adenosine (group B: n = 6), or Carolina rinse (group C: n = 7). Microvascular perfusion and WBC accumulation were assessed by intravital fluorescence microscopy. In group C, acinar perfusion was significantly improved, accompanied by a lower percentage of nonperfused sinusoids 1 hr after reperfusion (mean +/- SEM: 26 +/- 2% [group A], 21 +/- 2% [B], 11 +/- 1% [C], P < 0.01 for C vs. A or B). In addition, Carolina rinse and, to a lesser extent, adenosine rinse reduced the number of WBC sticking in sinusoids and postsinusoidal venules. Better graft function in group C was indicated by increased bile flow during the observation period of 90 min after reperfusion (0.5 +/- 0.3 ml/100 g liver [group A], 1.5 +/- 0.7 [B], 3.7 +/- 0.6 [C], P < 0.01 for C vs. A or B). We conclude that Carolina rinse is able to improve early excretory hepatocellular function, microvascular perfusion, and intrahepatic WBC accumulation after prolonged cold ischemia and reperfusion, but adenosine is unlikely to be the key component of this rinse solution. PMID- 8497910 TI - Protein synthesis and gene expression in transplanted and postischemic livers. AB - The expression of some genes has been comparatively studied in transplanted rat liver and in liver reperfused after ischemia in situ. Experiments on protein synthesis by tissue slices from cold-stored or transplanted livers show that rat livers that retain a good capacity for protein synthesis during storage undergo a profound impairment in the capacity for protein synthesis during the first hours after transplantation. This recovers in the following hours. There is never any indication of synthesis of stress proteins, and of hsp 70 in particular. The steady-state level of mRNAs for albumin, transferrin, and beta-actin, which are well expressed in reperfused postischemic livers in vivo, are reduced early after transplantation and recover only many hours later. Run-on analysis shows that an early defect in transcription and a partial recovery of this process later on are responsible for these changes. The steady-state levels of the same mRNAs are well maintained in donor livers preserved in University of Wisconsin solution for at least 12 hr, and less satisfactorily in Euro-Collins solution. Results of run-on analysis parallel the data on mRNA levels. The behavior of these mRNAs is, therefore, clearly different in reperfused and transplanted liver. The early stages of liver transplantation seem to be characterized by a depressed capacity of gene expression, without the reactive phenomenon of activation of stress protein genes that occurs in reperfused postischemic livers. PMID- 8497911 TI - Glomerular filtration rates in persons evaluated as living-related donors--are our standards too high? AB - We have retrospectively analyzed the glomerular filtration rate by 125-I iothalamate clearance and creatinine clearance in a group of 661 persons evaluated as potential kidney donors. The average GFR in this population is lower than that reported in previous studies and ranges from 102 +/- 15 and 114 +/- 17 ml/min for males and females age 21-30 to 84 +/- 13 and 79 +/- 15 ml/min for males and females age 51-60. Furthermore, there has been a gradual decrease in GFR in this population from 1970 to 1990 in both the entire population and in those under the age of 40. The cause of this drop is not apparent. These data can be utilized to determine the appropriateness of a potential donor for donation, and may indicate that our current standards are too high. PMID- 8497912 TI - The adverse impact of high cyclosporine. Clearance rates on the incidences of acute rejection and graft loss. AB - The influence of cyclosporine pharmacokinetic parameters on clinical events and outcome after transplantation was studied in 100 renal transplant recipients who underwent a pre- as well as posttransplant CsA pharmacokinetic evaluation. Among the patients, 30 were black and 50 were white. Black recipients had significantly lower bioavailability (F) pre- as well as posttransplantation than white recipients, the posttransplant mean F values being 25.8 +/- 9.0% and 38.1 +/- 16.7%, respectively (P < 0.002). The posttransplant CsA clearance rate (CL) and oral clearance (clearance/bioavailability; CLoral) were significantly higher in patients who had acute rejection than in those who did not, with CL mean values of 425 +/- 141 ml/min and 359 +/- 131 ml/min, respectively (P < 0.02). The initial posttransplant F was significantly lower, and the CLoral higher in patients who eventually lost their grafts than in those who did not, the mean F values being 26.5 +/- 12.8% and 38.7 +/- 17.5%, respectively (P < 0.002). Thus, several important relationships between CsA pharmacokinetic parameters and clinical events following renal transplantation were documented. The CLoral decreased during the first 3 months after transplantation (P < 0.0001), but it was stable thereafter. Neither the bioavailability nor the clearance of CsA showed a correlation with administered dose. These results indicate that certain recipient groups, such as black patients, and individuals with rapid CL, may benefit from larger CsA doses and/or shorter dosage intervals, in order to compensate for these interpatient variabilities. PMID- 8497913 TI - Early versus late acute renal allograft rejection: impact on chronic rejection. AB - We studied the effect of acute renal allograft rejection and its timing on the development of chronic rejection and subsequent graft loss. Between January 1, 1987 and April 30, 1991, 424 patients at the University of Minnesota received a primary kidney transplant (minimum follow-up, 1 year). Patients were subdivided by donor source, presence or absence of acute rejection, and the timing of acute rejection onset (early, < or = 60 days vs. late, > 60 days post-transplant). For living donor (LD) transplant recipients (n = 219), the incidence of chronic rejection is 0.8% in those who had no acute rejection (n = 130), 20% in those with acute rejection < or = 60 days (n = 59) (P < 0.001 vs. no acute rejection), and 43% in those with acute rejection > 60 days (n = 30) (P < 0.001 vs. no acute rejection, P = 0.04 vs. early acute rejection). For cadaver (CAD) transplant recipients (n = 205), the incidence of chronic rejection is 0% in those who had no acute rejection (n = 109), 36% in those with acute rejection < or = 60 days (n = 69) (P < 0.001 vs. no acute rejection), and 63% in those with acute rejection > 60 days (n = 27) (P < 0.001 vs. no acute rejection, P = 0.03 vs. early acute rejection). For both LD and CAD recipients, no grafts have been lost to chronic rejection among those who did not first have at least 1 acute rejection episode. In contrast, 23 patients with acute rejection have had graft loss to chronic rejection. For both LD and CAD recipients, those with > 1 acute rejection episode had significantly more chronic rejection than those with only 1 rejection (P < 0.05). There was no significant difference in the incidence of chronic rejection based on whether the first acute rejection episode was steroid resistant or steroid responsive. We conclude that acute rejection is strongly related to the development of biopsy-proven chronic rejection and subsequent graft loss. Patients undergoing their first acute rejection episode > 60 days (vs. < or = 60 days) have an increased incidence of chronic rejection. PMID- 8497914 TI - In vitro studies to explain high renal allograft survival in IgA nephropathy patients. AB - The pretransplant sera of 27 IgA nephropathy (N) kidney transplant patients were investigated for antibodies to the HLA molecule, together with 104 sera from non IgA N patients and 60 controls. IgA antibodies to HLA were found in 61% of IgA N patients and 2% of non-IgA N patients. IgA N patients with IgA antibodies to HLA had a 100% 2-year cadaver donor graft survival rate compared with 70% in those without IgA antibodies. Patients with IgG antibodies to HLA without accompanying IgA antibodies had the worst graft survival rates. We propose that IgA anti-HLA contributes to the high kidney graft survival in IgA N patients by blocking IgG antibodies or inhibiting cellular immune response. PMID- 8497915 TI - Radiobiologic and pathologic characteristics of the irradiated lung and roentgenographic aspects. AB - AIMS: Experimental radiobiologic factors help to better understand and interpret the development of radiographic alterations in lung tissues due to radiant treatments. In this paper the authors summarize the radiologic factors and technical bases about radiotherapy of the lung. METHODS: The conventional radiologic iconography has been examined in a large series of patients (n = 2151) with iatrogenic pulmonary lesions determined by various types of antineoplastic radiant treatments at the Istituto Nazionale Tumori of Milan. RESULTS: A radiologic control and a long follow-up is essential to assess the successive phases of postactinic lesions due to "passive" irradiation therapy for any type of non-endothoracic tumor as well as those due to "necessary" lung radiotherapy for endothoracic neoplasms. CONCLUSIONS: A strict relation has been found between the aspects in conventional radiologic iconography and the corresponding lesions in the irradiated lung. PMID- 8497916 TI - Testing cervicography and cervicoscopy as screening tests for cervical cancer. AB - AIMS AND BACKGROUND: Suboptimal sensitivity is currently reported for Pap test in screening for cervical cancer. Colposcopy is known to be more sensitive than cytology but its use as a screening test is not possible due to costs and complexity. Screening by cervicography has been suggested as a compromise being less costly and feasible. The present study evaluates the feasibility of screening by cervicography and cervicoscopy (naked eye examination of the cervix after acetic acid lavage) on a consecutive screening series. METHODS: Cervicography and cervicoscopy were performed by the smear taker in subjects consecutively attending a screening clinic. Women with abnormal cytology (atypia or more severe lesion) and/or abnormal cervicography or cervicoscopy (acetowhite lesion) underwent colposcopic assessment. The three screening methods were compared according to positivity rate, CIN 2-3 detection rate and positive predictive value. RESULTS: 2105 consecutive subjects were screened. Positivity rate was 3.8%, 15.3% or 25.4% for cytology, cervicography or cervicoscopy, respectively, 486 of 555 women attended the assessment phase, 281 directed biopsies were performed and 8 CIN 2-3 lesions were detected. Cytology, cervicography and cervicoscopy, detected 5.5, or 7 of 8 CIN 2-3 lesions, respectively. The positive predictive value was 0% for cytologic atypia, 25% for cytologic SIL, 1.75% for cervicography and 2.05% for cervicoscopy. Detecting one CIN 2-3 lesion at cytology cost $5,543. The cost per each additional cytologically negative CIN 2-3 lesion detected at cervicography or cervicoscopy was $12,947 or $3,916, respectively. CONCLUSIONS: The study confirms the limited sensitivity of cytology for CIN 2-3. The association of cervicography was not cost effective. Cervicoscopy was poorly specific but increased the detection rate of CIN 2-3 at relatively low costs. Cervicoscopy is worth further evaluation as a screening test. PMID- 8497917 TI - First results of a mammographic screening program in two municipalities of Massa Carrara Province (Italy). AB - AIMS AND BACKGROUND: A mammographic screening for breast cancer was started in 1989 in two municipalities of Massa-Carrara province. This paper describes the results of the first two years and evaluates the quality of the program via early indicators. METHODS: We calculated the attendance rate at first screening, the proportion of women recalled for further examinations (recall rate), the ratio between benign lesions and carcinomas detected by screening, the staging of the screen detected cancers and the ratio between detection rate and expected incidence (P/I ratio). RESULTS: Out of 14826 invited women 10407 (70.2%) attended the first screening; 266 (2.6%) of them were referred for further investigations but only 63 (0.6%) required surgical biopsy. A histological confirmed malignancy was found in 39 women corresponding to a detection rate of 3.7/1000. According to pTNM classification 89.1% of all cancers were either Tis or in stage T1; and in two third of the cases there was no nodes involvement. CONCLUSION: The results achieved so far, evaluated via early indicators, show a good start of the program. PMID- 8497918 TI - Medical oncology and home care in Italy. AB - AIMS AND BACKGROUND: Home care programs are designed to provide care for cancer patients in their homes. Aim of the study is to describe the activities of home care program, to examine the organization and efficiency of this type of care in Italy. METHODS: A questionnaire was sent to the regional representatives of the National Society of Medical Oncology and to the regional health departments. RESULTS: a) the home care program is uniformly distributed throughout the country; b) the number of personnel in the different centers varies greatly from one area to another; c) approximately 50% of the centers do not cover emergency situations (at night or on holidays); and d) there is little involvement of the public sector. CONCLUSIONS: In spite of these problems, the home care system is taking on a fundamental role, especially for advanced cancer patients. PMID- 8497919 TI - Endoscopic treatment of postradiation strictures. AB - BACKGROUND: Esophageal stricture is a rare complication of radiotherapy: reports on its incidence and management are therefore anecdotal. METHODS: From January 1978 to September 1992, 44 patients presenting with an esophageal stricture related to a previous radiation treatment were endoscopically dilated at the Endoscopy Division of the Istituto Nazionale Tumori of Milan. RESULTS: Esophageal recanalization was obtained in 95% of the patients treated, and in 79% of these normal eating habits were restored. No strict correlation was observed between radiation dose and severity of the stricture, or time elapsed between first treatment and endoscopic dilation. CONCLUSIONS: In our experience, endoscopic dilation was a safe effective procedure and represented an effective palliative tool in dysphagic patients with esophageal strictures due to previous local radiotherapy. PMID- 8497921 TI - Primary carcinoma of the fallopian tube. AB - BACKGROUND: Because of the rarity of fallopian tube cancer, clinical approaches have changed during the last 18 years. METHODS: Twenty-nine patients with fallopian tube cancer were treated at the Gynecologic Oncology Department of Milan University from 1970 to 1988. The mean patient age was 59 years. Parity, symptomatology and histology were considered. Distribution by stage was as follows: I, 11 (37%); II, 10 (34%); III, 8 (27%) according to the Dodson classification. Twenty patients (69%) underwent surgery followed by pelvic irradiation. Adjuvant chemotherapy was performed in the treatment of 5 women with stage I disease, 6 with stage II, and all 8 with stage III. RESULTS: Five-year overall survival was 41.38%: 47.6% at stages I and II, 25% at stage III. Radiotherapy has not been replaced by cisplatin-based multiagent chemotherapy. Optimal surgical debulking combined with accurate lymph node sampling are not followed by systematic use of repeat laparotomy. CONCLUSIONS: The procedures described in this work improve the clinical assessment and patient survival, and make different series comparable. PMID- 8497920 TI - A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity. AB - AIMS AND BACKGROUND: The clinical use of cisplatin (CDDP), one of the most active agents in advanced ovarian cancer, is limited by nephrotoxicity and cumulative neurotoxicity. In preclinical studies, reduced glutathione (GSH) demonstrated a protective action against CDDP nephrotoxicity. We treated 20 patients with advanced ovarian carcinoma, with polychemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. METHODS: Between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-IV-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cyclophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v. in normal saline 100 ml (in 15 min), before CDDP, every 21-28 days. RESULTS: A pathologic complete response rate (PCR) of 55% (11/20) was observed (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicity was limited, without any case of nephrotoxicity. CONCLUSIONS: On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies. PMID- 8497922 TI - A weekly schedule of epirubicin in pretreated advanced breast cancer. AB - AIMS: Epirubicin is an analogue of doxorubicin with a similar activity but less toxicity. The aim of this study was to evaluate the efficacy and the tolerability of a weekly schedule of epirubicin. METHODS: Fifty-three patients with metastatic breast cancer, pretreated and/or with a low performance status, were treated with 25 mg/m2/week of the drug. RESULTS: Of the 49 evaluable patients, 3 achieved a complete response (6.1%) and 21 a partial response (42.8%) with a median duration of 6.3 months. Median survival was significantly higher in responders than in nonresponders: 15.2 vs 6.0 months (P < 0.005). Furthermore, a marked improvement in performance status was observed (ECOG scale). No cardiologic toxicity was observed, and gastrointestinal toxicity was low. CONCLUSIONS: Epirubicin administered weekly represent a valid alternative to conventional treatments. PMID- 8497923 TI - Conservative treatment for T2-T4 bladder cancer with primary chemotherapy and radiotherapy: a pilot study. AB - AIMS AND BACKGROUND: After radical cystectomy, with or without pelvic radiotherapy, more than 50% of patients affected by infiltrating bladder cancer died of distant metastases. Polychemotherapy yields 25% complete remissions (CR) in patients with invasive transitional cell bladder carcinoma; although many concerns exist about the duration of such CR. This study was undertaken with the aim of evaluating the efficacy and safety of an integrated chemo-radiotherapeutic treatment, in order to broaden indications to a conservative surgical therapy. METHODS: Thirty-three consecutive patients with bladder urothelial cancer T2-T4, N0, M0, have been treated. Patients received neoadjuvant chemotherapy (rescue-M VEC) consisted of methotrexate 30 mg/sqm plus folinic acid 15 mg after 24 h on days 1, 15, 22; vinblastine 3 mg/sqm on days 1, 15 and 22; epidoxorubicin 30 mg/sqm on day 1; cisplatin 70 mg/sqm on day 1. This cycle was repeated on day 29. After 2 cycles of rescue-M-VEC, patients underwent pelvic cobalt teletherapy 40 Gy combined with low dose cisplatin 25 mg/sqm/week. After restaging, responding patients underwent further radiation therapy (24 Gy) as booster consolidation. RESULTS: After 2 cycles of chemotherapy and pelvic radiotherapy 14/31 evaluable patients (45.2%) achieved CR and 11/31 (35.4%) partial remission, with an overall response rate of 80.6% (25/31). With a median follow up of 21 months the actuarial survival rate at 24 months was equal to 79.8%. Eleven radical cystectomies were performed, 6 of which at restaging in non responding patients and 5 during the follow up due to relapse. Of the 25 patients selected for bladder conservation, 12 (48%) have not yet shown relapses. Three out of 31 (9.7%) patients died of distant metastases. No severe toxicity has been observed: moreover no patient developed stomatitis after chemotherapy. CONCLUSIONS: Our results seem encouraging but longer follow-up and further phase III studies need to be carried out to demonstrate the feasibility of conservative treatment in muscle infiltrating bladder cancer. PMID- 8497924 TI - Granulocytic sarcoma with myxoid stroma. Report of a case. AB - A granulocytic sarcoma with myxoid features simulating a chondrosarcoma was detected in the left arm of a 59 years old man. It is suggested that extramedullary hematopoietic neoplasms such as granulocytic sarcoma may display, similarly to malignant lymphomas, non-specific sarcoma-like features that obscure the usual diagnostic characteristics. PMID- 8497925 TI - Reduction of leukopenia in mice by "viscum album" administration during radiation and chemotherapy. AB - "Viscum album" extract, iscador, was found to reduce the leukocytopenia produced by radiation and cyclophosphamide treatment in animals. Weight loss due to radiation was considerably reduced by "Viscum album" extract whereas weight loss due to cyclophosphamide was not altered. Hemoglobin levels also were not affected by "Viscum album" extract administration. The results indicated that treatment with "Viscum album" extract reduces lymphocytopenia and hence could be used along with chemotherapy and radiation therapy. PMID- 8497926 TI - Cancer research in the European Community and other non-EC countries. AB - AIMS: We assessed the scientific productivity in the field of cancer research of countries in the European Community (EC) and the most important non-EC countries by counting the number of papers published during the period 1988-1990 in 15 of the top scientific journals (as defined by the Journal Citation Reports, Oncology). The global and per capita data are presented for each country. METHODS: Qualitative parameters like the impact factor and the half-life were also considered in the analysis. The selection of cancer journals with a high average quotation rate gave significant results. Introducing the average impact factor and half-life of each journal modified the results only slightly. The per capita data for each country were not corrected for the number of investigators working in oncology (a datum difficult to obtain). The parameters thus do not define the performance of the average investigator but are more "economic" parameters specifically related to the field of cancer research. RESULTS AND CONCLUSIONS: Small, wealthy Western countries tended to have an advantage over large, less developed countries, as expected. However, additional individual differences that could be of interest were present in the group of developed countries. PMID- 8497927 TI - [Infertility and the work environment]. PMID- 8497928 TI - [Reversible reduction of semen quality during occupational exposure to radiating heat]. PMID- 8497929 TI - [Significance of occupational factors for women's fertility and menstrual cycles]. AB - Reduced fertility is frequent, reflected by the fact that 15% of all couples desiring pregnancy try for more than one year without achieving it. Women at work are often exposed to chemical or physical agents, some of which are carcinogenic or teratogenic. Fertility seems to be affected by exposure to lead, mercury, solvents, textile dyes, noise and some pesticides. The purpose of this paper is to summarize the current knowledge of the relations between fertility, menstrual irregularity and occupational exposures. There are still some methodological problems to be solved in relation to fertility. Waiting time to pregnancy seems to be an appropriate measure of fertility. The full distribution of time to pregnancy over months or menstrual cycles should be used in the analysis. PMID- 8497930 TI - [Occupational medical research of male reproductive capacity]. AB - During the past 15 years, approximately 50 occupational medical sperm quality investigations have been carried out in the world as a whole. The discovery of reduced testicular function among workers exposed to the chemical agent dibromochloropropane (DBCP) was an important incitment for the conduct of these investigations. These have not demonstrated new occupational medical influences with as dramatic an effect as DBCP but moderately reduced sperm quality has, however, been proved or suspected after occupational exposure to a series of other agents: certain cell poisons (ethylene dibromide, carbaryl, chlordecone), certain glycoethers (in paint, glue, printing inks, antifreeze solutions), certain organic solvents e.g. styrene (plastic casting), choroprene (plastic production), low exposure to lead, metal welding, thermal influences and high frequent electromagnetic fields (300 kHz-300 mHz). Only a few investigations illustrate the significance of the male factors for infertility and delay before deliberate pregnancy and there are still no well-proved examples of human paternal teratogenic agents or carcinogens. Our present knowledge only serves to prevent a limited proportion of reproductory failure in men. Reports of decreased sperm quality in the population and the influence of the environment on reproduction in domestic animals indicate that further investigations are necessary. Longitudinal investigations of sperm quality together with investigations of fertility or delay till deliberate pregnancy are proposed subjects for future strategy. PMID- 8497931 TI - [Description, evaluation and clinical decision making based on various cardiotocograms. Observers and regional variability]. PMID- 8497932 TI - [Intraobserver and interobserver variation in measurement of the pelvic diameter using DeLee's internal pelvimeter in Cesarean section]. AB - The method of measuring the true conjugata with DeLee's Internal Pelviometer at caesarean section was evaluated. In 58 women the true conjugata were blindly measured three times by the surgeon and also, in fifty cases, three times by the assistant. Only a slight intraobserver difference was found: median range was 0.42 cm. There was no significant interobserver variation. We conclude that DeLee's Internal Pelviometer can be used to measure the true conjugata at caesarean section, but the use of pelviometry in modern obstetrics is questioned. PMID- 8497933 TI - [Knowledge about asthma among Danish primary school teachers. Results of a questionnaire study]. AB - An anonymous questionnaire inquiry performed among 324 school teachers in the Randers area with the purpose of elucidating teachers' knowledge about asthma is presented. To a series of statements about asthma, the teachers should answer yes, no or don't know. A limited knowledge about asthma in children was found. The knowledge about medicamental treatment was particularly limited. Only 57 per cent knew that wheezing after physical exertion is a strong indicator of asthma. Only five per cent had received proper instruction. This latter group had a significantly better knowledge of medical treatment (p < 0.0001-0.05). It is recommended that instruction in children's diseases, especially asthma should be reintroduced in teachers' training colleges. PMID- 8497934 TI - [Purulent arthritis and bursitis after local injection of depot steroids]. AB - The occurrence of severe joint and bursal infections preceded by local steroid injection was investigated in a retrospective survey. Of 37 consecutive patients with pyogenic arthritis or bursitis admitted to two hospitals over a three-year period, nine (95% confidence limits 12-41%) had received previous intraarticular or intrabursal injections of steroid. Staphylococcus aureus was cultured in all cases. This incidence rate of endemic iatrogenic infection is at least 60 times higher than earlier reported. The alarming frequency may be attributed to insufficient aseptic precautions and/or the injection of depot steroids into cavities with overlooked established infection. An increased awareness of this complication seems warranted. Meticulous hygienic measures should be emphasized in drug information inserts. Health authorities and quality control bodies should monitor and analyze the occurrence of such accidents. PMID- 8497935 TI - [Long-term prognosis in patients with mechanical aortic valves without anticoagulant therapy. A follow-up study over 1-15 years]. PMID- 8497936 TI - [Speech rehabilitation after laryngectomy, primary insertion of a speech ventilator]. AB - During a period of three years, 30 patients were submitted to laryngectomy in our department. In 23 of these, primary tracho-oesophageal puncture had been performed and secondary puncture was performed in one patient. Fifteen of the prostheses were of the Blom Singer type and nine were Provox prostheses. Twenty one patients learned to use the voice prosthesis and obtained fluent or understandable speech while three patients never used the prosthesis. Three patients subsequently abandoned the speech prosthesis and preferred to continue using oesophageal speech. Side effects were restricted to leakage around the prosthesis and slight stenosis in the pharyngo-oesophageal segment. PMID- 8497937 TI - [Mirizzi syndrome. A rare complication of gallstones diagnosed by endoscopic retrograde cholangiopancreatography]. AB - The Mirizzi syndrome is recognized as an external compression of the common hepatic duct by a calculus impacted in the cystic duct. Although it is a rare condition, the diagnosis is important because of the resemblance to malignant strictures in the biliary tract. Two cases diagnosed preoperatively by ERCP are reported. PMID- 8497938 TI - [Hereditary pancreatitis]. AB - Hereditary pancreatitis (HP) is an uncommon disorder previously described in only two Danish families. A third family with HP is presented. The diagnosis of HP should be considered in a child with unexplained relapsing abdominal pain, and in particular with a positive family history. PMID- 8497939 TI - [Mammographic screening]. PMID- 8497940 TI - [Spontaneous course of perinatally diagnosed hydronephrosis]. PMID- 8497941 TI - [Autologous bone marrow transplantation]. PMID- 8497942 TI - [Contalgin and Doltard--2 different morphine depot preparations]. PMID- 8497943 TI - [Being a visiting scientist in Japan, an interesting challenge]. PMID- 8497944 TI - [Septomonab (Centoxin) in the treatment of gram-negative septicemia]. PMID- 8497945 TI - [Prevention of aspiration in obstetric patients]. PMID- 8497946 TI - [Prevention of aspiration in obstetric patients in Denmark]. AB - Women about to undergo Caesarean section are especially prone to suffer from aspiration of acid gastric contents into the lungs during anaesthesia. Physiological changes in the pregnant patient make gastric emptying time unpredictable. It therefore seems prudent to establish procedures in order to minimize the risk of aspiration of gastric contents. This survey reveals that 25% of the obstetric-anaesthesiological departments in Denmark employ pharmacological prophylaxis for aspiration of acid gastric contents. This finding is in contrast to a similar survey in the United Kingdom, where 99 to 100% of the Caesarean sections are carried out under pharmacological prophylaxis for aspiration of acid gastric contents. PMID- 8497947 TI - [Congenital hearing disability among children in Copenhagen]. AB - The survey describes the detection, identification and aetiology of congenital/early acquired (i.e. neonatal period) hearing disability in a well defined cohort of children, living in the Copenhagen area (Copenhagen City and County). The effect of intervention programmes is also mentioned. The children's age at identification can be considered as an evaluation of the quality of hearing screening aimed towards the detection of children with congenital/early acquired hearing disability, while the results of the aetiological evaluation reflects the quality of the diagnostic evaluations performed within paediatric audiology. The prevalence rate of 1.5/1000 of congenital/early acquired hearing disability for children born during 1980-1990 is unchanged in comparison to the period 1970-1980. An improvement in the detection of children with congenital/early acquired hearing disability is found, the identification is, however, still delayed in both children at risk and not-at-risk of hearing disability. The parents are most frequently the first to raise suspicion of their child's hearing disability, but very seldom apply to the audiological department without a referral from the primary health care sector. A change in the aetiology of congenital/early acquired hearing disability has taken place within 1980-1990, which can be ascribed to the reduced frequency of foetal rubella infection, while the frequency of inherited hearing disability has increased. The outcome of intervention programmes, evaluated by means of type of school, education, and employment situation is briefly described in relation to the social consequences of a hearing disability. PMID- 8497948 TI - [The bone-anchored hearing aid. Host-reaction and audiological effect]. PMID- 8497949 TI - [Prominent ears. Normal distance between the auricular edge and the side of the head]. AB - The desire of the patients or their parents for surgical correction of protruding ears is not always in accord with the degree of deformity. As complications can not only ruin a good result but can make the situation worse, some degree of deformity must be present. In order to achieve some guidance in this evaluation we have measured the maximum distance between the side of the head and the helix border in 102 girls and 81 boys, aged 6-16 years. We found a range of ten to thirty-three. The mean value increased with age, and the distance in males was 2.89 mm greater than that found in females. PMID- 8497950 TI - [Panic disorder--a new diagnosis. Clinical picture and treatment]. AB - Panic disorder (DSM-III, DSM-III-R) has been thoroughly studied in recent years. A review of the main evidence for panic disorder as a nosological entity is given, in order to delineate some important questions for future research. Validation criteria considered include epidemiological, phenomenological, genetic, neurobiological, pharmacological and behavioral findings. Biological, behavioral and psychodynamic considerations on etiology, pathogenesis and treatment are presented. PMID- 8497951 TI - [Panic disorder. The pattern of somatic contacts in patients]. AB - The epidemiology, phenomenology and treatment of panic disorder have been thoroughly studied in recent years. The symptomatology of panic attacks may mimic cardiopulmonary, neurological and gastrointestinal disease. Forty Danish panic patients with panic disorder of ten years' duration had had contact with several medical specialists, hospital emergency and outpatient services. Thus, 28% had visited neurologists, 8% cardiologists and 20% an emergency service. One third had been admitted to hospital departments. Almost all patients had consulted psychiatrists or psychologists. Ninety had been treated with a benzodiazepine, 35% with tricyclic antidepressants and 57% with neuroleptics. To prevent costly medical testings and delay in accurate diagnosis in psychiatric and somatic settings, the phenomenology of panic disorders should be recognized by all medical specialists and general practitioners. PMID- 8497952 TI - [Complications of spinal anesthesia compared to general anesthesia. A prospective study of 408 consecutive orthopedic patients]. AB - In this prospective study the preoperative risk classification and pulmonary status was compared to postoperative mortality and morbidity, following either spinal or general anaesthesia. We studied 408 consecutive orthopaedic patients. Comparing the anaesthetic methods we found no differences in mortality or in frequency of cardiac complications, while the non-cardiac complications were seen more frequently in patients who had undergone spinal anaesthesia (p < 0.05). Patients from the lower risk groups with a preoperative abnormal pulmonary status had a higher frequency of postoperative pulmonary complications following spinal anaesthesia than following general anaesthesia (p = 0.015). IN CONCLUSION: 1) We find no difference in postoperative mortality depending on the anaesthetic method chosen, 2) the predictive value of the Boston Cardiac Risk index is identical for the two anaesthetic methods, and 3) the anaesthetic method of choice for the pulmonary disabled patient has not yet been established. PMID- 8497953 TI - [Early osteosynthesis of fractures of the lower extremities in patients with multiple trauma]. AB - In the early 1970s, some trauma centres began to perform early operative fixation of lower limb fractures in multiple trauma patients. At that time, no clinical studies were available on this topic. At present, several publications have demonstrated lower mortality, reduction of the incidence of Adult Respiratory Distress Syndrome and sepsis, and a shorter stay in hospital after early operative fracture fixation compared with conservative fracture management or late fracture fixation. The incidence of fracture complications appeared not to increase after early operative fracture fixation. The present paper is a review of the most significant reports concerning timing of operative fracture management of patients with multiple trauma. Prospective randomised trials are needed on this subject. PMID- 8497954 TI - [Work load and cardiovascular risk factors. A cross-sectional study of employed Danish men and women]. AB - As part of World Health Organisation initiated MONICA project, 2000 men and women aged 30, 40, 50 and 60 from the general population were invited to undergo a medical examination with special emphasis on cardiovascular disease. A total of 1504 (75%) participated, 1209 of whom were employed. The participants answered a questionnaire on working, social, and health conditions and underwent clinical examinations that included the measurement of blood pressure and serum cholesterol triglycerides, high density lipoprotein, fibrinogen and glycosylated haemoglobin (HbA1C) concentrations. Using the demand control model for measuring job strain suggested by Karasek, the employed people were classified according to those who had suffered job strain and those who had not in two different ways. The subjective classification was based on the participants' statements regarding demand and control in their jobs, whereas the objective classification was based on job title and mode of payment. More women than men were classified as having high strain jobs. After adjusting for age and sex no significant association was found between coronary risk factors and subjective job strain. A tendency for an association between fibrinogen and job strain was found. Body mass index and HbA1C concentration were significantly associated with objective job strain independent of confounders. PMID- 8497955 TI - [Cardiac arrhythmias after transmediastinal resection of the esophagus]. AB - A study of 45 patients who underwent blunt transmediastinal resection of the esophagus without thoracotomy is presented. Sixteen patients (38%) developed a cardiac arrhythmia. The most common arrhythmia was atrial fibrillation/flutter. Even though 14 of the arrhythmias (88%) converted to sinus rhythm, a significantly higher death-rate was seen in this group of patients (p < 0.0014). As we suspect a relation between cardiac arrhythmia and increased mortality after this type of operation, we propose that a double-blind study should be carried out in order to determine the value of an antiarrhythmic treatment. PMID- 8497956 TI - [Paraclinical examination programs in Danish hospitals prior to minor surgical procedures]. AB - Using a questionnaire, paraclinical test programs prior to minor surgery were recorded for Danish hospitals. Sixty-one out of 66 departments of surgery completed the questionnaire. Most of the departments used a basic test program for younger subjects and an extended one for elderly subjects. The most commonly used investigations were in descending order: analysis of urine for glucose, albumin and hemoglobin, B-Hemoglobin, blood typing, P-Creatinine, and P-Potassium and Sodium. In elderly persons, ECG and a chest radiograph were used rather frequently in addition. The number of tests ranged from zero to nine (median three) for younger patients and from two to ten (median six) for elderly subjects. The estimated costs of the programs ranged from zero to 1092 Danish crowns (109 pounds) (median 185) for younger patients and from 71 to 1676 Danish crowns (167 pounds) (median 714) for elderly patients. In conclusion, the variation in the extent and estimated costs of preoperative test programs used in Danish hospitals is considerable. PMID- 8497957 TI - [The phenacetin kidney--still in the 1990's]. AB - A case of adverse effects of phenacetin is described, and followed by a discussion about the continued use of this drug in Denmark even though it was removed from the pharmacopoeia in 1984. It is stressed, that the free right of prescription enables doctors to continue prescribing drugs, that have been deregistered by the health authorities, and on a scale that is not surveyed by the Statistics of Remedies. PMID- 8497959 TI - [Can hearing tests prevent hearing loss in the occupational environment?]. PMID- 8497958 TI - [Dilated cardiomyopathy in a user of anabolic steroids]. AB - A case is described in which a 32-year old male body-builder was admitted with signs of cardiac incompensation after using anabolic steroids (AS) in large amounts for three weeks before admittance. Echo-cardiography showed a dilated left ventricle with decreased systolic function and electrocardiography showed atrial fibrillation. Response to treatment was good and he was discharged to further out-patient treatment. After nine weeks he was admitted with severe cardiac incompensation. There was no response to treatment and he died after three days. At autopsy the heart weighted 527 grams and was diffusely dilated. There were no signs of infarction. Microscopy showed scattered lymphocyte infiltrates consistent with dilated cardiomyopathy, possibly caused by myocarditis. There were no signs of bacterial infection, the patient was a non alcoholic and no other known cause of myocarditis was shown. We conclude that the patient died from toxic myocarditis with dilated cardiomyopathy caused by AS. PMID- 8497960 TI - [Orientation from the Drug Regulation Department of the National Board of Health and the Scientific Ethics Committee]. PMID- 8497961 TI - [Video display terminals and spontaneous abortions--one more time]. PMID- 8497962 TI - [On back training in low back pain]. PMID- 8497963 TI - [Neurocysticercosis?]. PMID- 8497964 TI - [Atrial fibrillation]. PMID- 8497965 TI - [Hyperthyroidism and heart disease. Is thyrotoxic cardiomyopathy a disease entity?]. AB - Cardiac symptoms have a prominent position in hyperthyroidism. The basic haemodynamic change is an increased cardiac output due to an increased stroke volume and an increased heart rate. Dyspnoea and palpitations are frequent symptoms. ECG-changes such as atrial fibrillation, sinus tachycardia, prolonged atrioventricular conduction and ST-segment changes are seen, but such changes are unspecific. Chest X-ray and echocardiographic studies are often normal, but cardiomegaly and ventricular hypertrophy are seen. The cardiac and non-cardiac symptoms of hyperthyroidism may in part be related to an increased sympathoadrenal activity. The thyroid hormones also exert a direct effect on the heart. Treatment includes specific anti-thyroid medication, beta-blocking agents, digoxin, diuretics and possibly anticoagulant therapy. Congestive heart failure, ventricular hypertrophy and arrhythmia are most commonly seen if other cardiac abnormalities are already present. The existence of thyrotoxic cardiomyopathy as an independent disease is illustrated by two case histories, which also demonstrate the reversibility of this condition. PMID- 8497966 TI - [Spinal stenosis. A review]. AB - Spinal stenosis is characterized by a broad spectrum of symptoms which are often vague. Therefore, patients suffering from this condition are typically seen by various specialists over a long period of time. Among the symptoms are various degrees of low back pain, neurogenic claudication, parasthesias, muscle weakness and reflex abnormalities. When spinal stenosis is suspected, CT-scanning seems to visualise stenosis well. Because the localisation of the stenosis is often unknown, myelography is still the first choice. CT-scanning can then provide supplementary information regarding the specific location. MR-scanning is not as yet used as a routine procedure, but will in time replace both procedures. Conservative treatment consisting in analgesics and physiotherapy is sufficient in some cases. When conservative treatment is not enough, surgical intervention consisting in decompression by broad laminectomy is performed. Fusion is performed when there are signs of vertebral instability or in young patients. Operational results are often good. Failure is seen following insufficient decompression. PMID- 8497967 TI - [Systemic chemotherapy in bladder cancer]. AB - This review reports the results of chemotherapy in advanced bladder cancer with emphasis on the latest studies concerning combination chemotherapy containing cisplatin and methotrexate. The main conclusion is, that chemotherapy has a tumor reducing effect on both metastatic disease and local/regional recurrences, but it remains to be proven whether overall long-term survival is affected. Among patients who respond to chemotherapy, the survival seems to be prolonged, 10-15% of these patients achieving more than two years of disease-free survival. The most effective treatment regimes contain cisplatin and methotrexate. It is assumed that many patients with muscle-invasive bladder tumors have microscopic dissemination of the disease at the time of diagnosis, and chemotherapy has been given to these patients as primary treatment alone or as an adjuvant to cystectomy or radiotherapy. These studies have not been able to show any benefit in terms of prolonged survival of patients receiving chemotherapy. The results of on-going randomised studies are still awaited. It is concluded that chemotherapy to patients with both primary and metastatic bladder cancer is still an experimental treatment, which should only be used in the context of investigational studies. PMID- 8497968 TI - [Hallucinogenic psilocybine-containing mushrooms. Patterns of use among Danish abusers]. PMID- 8497969 TI - [Assessment of risk in patients admitted for observation for suspected acute myocardial infarction based on a sensitive immunoanalysis of serum creatine kinase isoenzyme MB]. AB - We evaluated a new sensitive creatine kinase (CK) isoenzyme MB immunoassay with regard to clinical applicability and clinical outcome in 156 patients admitted consecutively to the Coronary Care Unit and suspected of having acute myocardial infarction (AMI). Sixty-five patients (42%) had AMI based on WHO criteria; 65 (42%) had ischemic heart disease (IHD) without AMI, and 26 (16%) had non-IHD. The 65 IHD-patients without AMI could be subdivided into a group of 24 patients with significant changes in serum CK MB levels and 41 patients with stable serum CK MB levels as compared to the non-IHD group. The cumulative cardiac survival after 2 1/2 year (i.e. not suffering cardiac death) was 95 +/- 3% for patients with stable CK MB levels; for those with changes in CK MB levels it was 66 +/- 10% (p < 0.003). It was 52 +/- 6% for the patients with AMI, similar to patients with changes in CK MB levels (p = 0.15). We conclude, that this new CK MB assay can, in patients with IHD without AMI, detect a sub-group, representing one-third of the patients in this group, which is not diagnosed using routine diagnostic procedures. These patients are characterized by a poor clinical outcome, similar to patients with definite AMI. PMID- 8497970 TI - [Urine samples for screening of asymptomatic Chlamydia trachomatis infection in young male recruits]. AB - A prevalence rate of asymptomatic Chlamydia trachomatis infection among young Danish male military conscripts of 7.8% in 1989 and of 10.8% in 1992 is presented. A urine sample seems to be as valid a specimen type as a conventional urethral swab for demonstrating presence of Chlamydia trachomatis antigen by either ELISA (Enzyme-linked immunosorbent assay) or DFM (Direct Fluorescent Microscopy). The method is noninvasive and very suitable for screening young men in order to control urogenital Chlamydia trachomatis infection. PMID- 8497971 TI - [Prognosis for the critically ischemic lower extremity when surgical revascularization is not possible]. AB - Of 427 patients with chronic critical ischemia of the lower extremity admitted for infrapopliteal bypass surgery, thirty-four (8%) were considered technically inoperable: in 26 cases due to total occlusion of the runoff vessels, and in eight due to a poor runoff and no suitable vein. The symptoms were rest pain in 24 cases and gangrenous ulceration in ten. During a follow-up of eight to twenty eight months five (15%) patients improved significantly, and complained only of claudication. Three patients, suffering rest pain, were unchanged at nine months follow-up, and 25 (74%) patients had a major amputation performed during the follow-up period. The remaining patient died the day after admission. The mortality rate of these patients was significantly increased compared to that of the 393 patients who underwent infrapopliteal bypass surgery, who in turn had a higher mortality rate than that of an age- and sex-matched Danish population. The group of patients who preserved their limb could not be identified by either ankle- and toe-pressure measurements or clinical evaluation. PMID- 8497972 TI - [Autologous transfusion of drained blood in hip and knee alloplasty. A prospective controlled study of 56 patients]. AB - Fifty-six patients undergoing hip or knee replacements were randomized to receive autologous drain-blood transfusion or homologous blood transfusion at postoperative need. A reinfusion of 65% of the postoperative drainage blood loss was achieved. The number of homologous blood transfusions fell concomitantly from 2.3 to 0.6 after hip replacement and from 3.3 to 0.3 after knee replacement. No signs of activation of the complement or coagulation systems were found. PMID- 8497973 TI - [Chordoma. An unusual cause of cauda equina syndrome]. AB - Acute cauda equina syndrome caused by a chordoma in the third lumbar vertebra is presented as a case report. This combination has not previously been described. PMID- 8497974 TI - [Localized nodular myositis--a variation of polymyositis]. AB - A case of focal nodular myositis is reported. The patient was a 37-year old male with no prior medical history. He had three episodes of focal nodular myositis over a three month period, recovering completely after each attack. During the last attack there were three lesions in the left quadriceps and one in the biceps muscle of the left arm. Histologically there was severe myositis. After the last attack he has been well for 12 months without sequelae. PMID- 8497975 TI - [Fatal hemostatic complications following erroneous thrombolytic therapy in patients with suspected acute myocardial infarction]. AB - This report describes the fate of two young men wrongly treated with thrombolysis for suspected myocardial infarction. Both had electrocardiographic changes upon admission. Correct diagnoses of aortic dissection and haemorrhagic pericarditis was obtained within a few hours, but, due to the prolonged disturbance of haemostasis, appropriate therapy could not be instituted, and outcome was fatal for both patients. These cases underline the importance of rigid ST criteria, and procedures for neutralization of thrombolysis are proposed. PMID- 8497976 TI - [Drug induced abortion]. PMID- 8497977 TI - [Transportation of sick newborn infants--an organizational problem]. PMID- 8497978 TI - Combined cholecystectomy and radical genitourinary cancer surgery. AB - We have routinely performed simultaneous cholecystectomy in patients with cholelithiasis undergoing selected radical genitourinary cancer surgery. A total of 31 patients have undergone cholecystectomy at the time of radical nephrectomy (25), radical cystectomy (5), and radical prostatectomy (1). Operative time was increased twenty-five to forty-five minutes. There was no significant increase in blood loss, postoperative total bilirubin, or number of complications. No complications were directly attributable to the cholecystectomy except for 1 patient who had prolonged drainage from a closed suction drain in the gallbladder fossa. We conclude that concomitant cholecystectomy at the time of radical genitourinary cancer surgery does not significantly increase morbidity and recommend that it be performed in the presence of cholelithiasis. PMID- 8497979 TI - Use of kidneys from older cadaver donors for renal transplantation. AB - From 1971-1990, 51 patients underwent renal transplantation with a kidney from a cadaver donor more than fifty-five years of age. Following transplantation, 19 kidneys (37%) functioned immediately while initial nonfunction occurred with 32 kidneys (63%). The one-year graft survival rate for kidneys with immediate function versus initial nonfunction was 84 percent and 63 percent, respectively. Graft survival was significantly impaired by increased recipient weight (p < 0.05) and by an elevated donor serum creatinine level (p < 0.05). We conclude that well-functioning kidneys from older donors can be safely and successfully used for renal transplantation. Such kidneys appear to be more susceptible to ischemic damage and should not be used when the donor serum creatinine level is elevated. PMID- 8497980 TI - Iodine 125 seed implants for prostatic carcinoma. Five- and ten-year follow-up. AB - Between 1975 and 1985 132 patients underwent bilateral pelvic lymphadenectomy and insertion of Iodine 125 seeds for biopsy-proved localized carcinoma of the prostate. Surgical stages were A2 9 percent, B 64 percent, C 9 percent, and D1 18 percent. Operative mortality was zero. Short and long-term complications were less than 33 percent. Ten-year survival rates of evaluable patients for surgical Stages A2, B1, B2, and C1 were 75 percent, 70 percent, 48 percent, and 44 percent, respectively. For these patients, ten-year disease-free rates for Stages A2, B1, B2, and C1 were 67 percent, 36 percent, 60 percent, and 25 percent, respectively. Interstitial radiotherapy may play a role in the treatment of nonsurgical candidates with low volume and well- to moderately-differentiated adenocarcinoma of the prostate. PMID- 8497981 TI - Management of the spastic urinary sphincter. AB - Alpha blockade is a well-established form of therapy for bladder outlet obstruction. We introduce a new drug to the regimen that appears to facilitate relaxation of both the bladder outlet and external sphincter mechanism in patients with a spastic urinary sphincter. PMID- 8497982 TI - Urethral polyp presenting as interlabial mass in young girls. AB - We describe two young girls who presented with an interlabial mass. Histologic examination of each excised mass revealed a benign urethral polyp covered with transitional and squamous epithelium. Urethral polyps should be included in the differential diagnosis of an interlabial mass in young female patients. PMID- 8497983 TI - Pseudoexstrophy. AB - Pseudoexstrophy is a rare, mild exstrophy variant which involves the major musculoskeletal defects of the exstrophy complex without any associated defect in the urinary system. A case is reported presenting at birth as an umbilical positional anomaly. Differential diagnosis and management are reviewed. PMID- 8497984 TI - Transient acute renal failure in the neonate. AB - We have observed a transient renal insufficiency in newborns associated with ultrasonographic finding of hyperechoic renal pyramids. This condition rapidly resolves, coinciding with both normalization of the renal ultrasound and the occurrence of significant proteinuria. Others have recognized a similar state of oliguria and cylindruria associated with a prolonged nephrogram on intravenous urography in newborns. There is evidence to suggest that hyaline cast deposition within the collecting tubules may account for these imaging abnormalities. The precise events surrounding the protein deposition are unknown, and it may be either the cause or the result from the transient renal dysfunction. Our 2 cases add to the evidence that there is a distinct entity of acute renal dysfunction, with identifying characteristics, in neonates associated with a good prognosis and rapid resolution. PMID- 8497985 TI - Staghorn calculi treated by percutaneous nephrolithotomy: risk factors for recurrence. AB - Since 1985 our primary mode of therapy for staghorn calculi has been by percutaneous nephrolithotomy. Between January 1985 and June 1988 we have treated 57 cases using this method. We reviewed the rate of recurrence at a minimum of one-year follow-up and observed a 17 percent recurrence rate. Factors identified that were associated with an increased rate of recurrence were: positive urine cultures during follow-up (55% recurrence vs 12%); stone remnant greater than 5 mm (27.3% recurrence vs 13.8%); and stone complexity (25% recurrence for complex or complete staghorn vs 9.7% for noncomplex or partial staghorn). By identifying these risk factors we think that stone recurrence can be reduced and, with close follow-up, detected earlier to permit less invasive therapy if needed. PMID- 8497987 TI - Simplified method for backloading of guidewire during endourology. PMID- 8497986 TI - Relapse on endocrine treatment in patients with stage D2 prostate cancer. Does second-line hormonal therapy affect survival? AB - Patients with Stage D2 prostate cancer relapsing on endocrine treatment have a grim prognosis. The role of a second-line hormonal treatment is debatable. We analyzed retrospectively, response and survival among 119 men (57 black, 62 white) progressing on a variety of first-line hormonal therapy. Sixty-one received a second-line hormonal treatment. Fifty-eight received only supportive therapy after first line therapy was discontinued. Age and race were not a factor in survival. Based on this retrospective study the optimal management for progressive metastatic prostate cancer cannot be delineated. However, the best results were in patients treated with diethylstilbestrol (DES) as a single treatment or when employed as either first or second treatment in patients receiving two therapies. The other modalities, e.g., bilateral orchiectomy, LH-RH analogues, and anti-androgens resulted in comparable outcomes when used either as single treatment or in combinations. Further clarification of the trends shown in this report require randomized controlled studies. PMID- 8497988 TI - Sigmoid colon carcinoma metastatic to prostate. AB - Although primary prostatic carcinoma is very common, prostatic metastasis is unusual. We describe a unique example of prostatic metastasis from noncontiguous colon cancer, after presumed curative resection of the primary tumor. Potential mechanisms of metastasis are examined in the context of clinical and histopathologic evidence. A possible role is proposed for early transrectal ultrasound examination in diagnosis of patients with unexplained urologic symptoms after resection of colorectal cancer. PMID- 8497989 TI - Complete ureteral replacement by Boari bladder flap after cadaveric renal transplant. AB - Boari bladder flaps are generally used to bridge a loss of distal ureter in ureteric reconstruction, especially after ureteric injury during pelvic surgery. Herein is reported a case of total ureteral replacement in a cadaveric renal allograft fifteen days after initial implant, for total ischemic loss of the donor ureter. PMID- 8497990 TI - Renal sarcoidosis coexisting with hypernephroma. AB - Hypernephroma arising in a kidney infiltrated by sarcoidosis is unusual. To date, there has been no such case reported. The hypernephroma was suspected by the presence of localized parenchymal calcifications and confirmed by selective renal angiography. PMID- 8497991 TI - DNA profile of nephrogenic adenoma assessed by flow cytometry. AB - Nephrogenic adenoma is a metaplastic condition which usually involves the bladder urothelium within the clinical setting of chronic inflammation. Its presentation/endoscopic appearance may mimic bladder cancer and a premalignant potential has been speculated. DNA flow cytometry performed on involved bladder tissue revealed a diploid phenotype exhibiting low proliferative activity. These findings are most suggestive of a benign process. PMID- 8497992 TI - Castleman disease. Unusual retroperitoneal location indistinguishable from malignant tumor in preoperative angiographic appearance. AB - Castleman disease (angiofollicular lymph node hyperplasia) has been reported rarely as a solitary retroperitoneal mass radiographically indistinguishable from retroperitoneal malignancies. We report a case of a hyaline-vascular variant of Castleman disease presenting as a pararenal mass. The computerized tomographic and angiographic appearances of this lesion are presented, and the clinical importance of the differential diagnosis of retroperitoneal tumors is discussed. PMID- 8497993 TI - Acquired cystic kidney disease: the hormonal hypothesis. AB - Based on the reported sex difference in the incidence of acquired cystic kidney disease (ACKD) in patients with chronic renal failure, it is hypothesized that the hormonal derangement, well documented in male and female uremic patients on long-term dialysis, could be responsible for the pathogenesis of ACKD. The decreased androgen/estrogen ratio, and the increased estrogen value could be responsible for an estrogen receptor mediated effect on the tubular epithelial cell proliferation, an event further potentiated by the action of regulatory peptides like epidermal growth factor (EGF). The epithelial stimulation is more pronounced in men because male tissues are less adapted than female tissues to high estrogen values. Furthermore the androgen reduction, more remarkable in male than female patients, is responsible for an up-regulation of EGF-R. Therefore hormones and growth factors, by means of their own receptor in renal tissue (homologous to the two oncogenes c-erb A and c-erb B), may be responsible for the development of ACKD, and may play an important role in the pathogenesis of multiple adenomas and renal carcinomas reported with high incidence among uremic patients with ACKD. PMID- 8497994 TI - Mullerian duct cyst. Case report with diagnosis established by transrectal prostatic ultrasound. AB - A case is reported of mullerian duct cyst diagnosed by transrectal prostatic ultrasound in a twenty-eight-year-old white man presenting with symptoms of obstruction. A review of the symptoms and treatment found in the literature is presented. PMID- 8497995 TI - Renal cell carcinoma extending into left side of double inferior vena cava. AB - A case of renal cell carcinoma extending into the left side of a double inferior vena cava is presented. En bloc excision of the left inferior vena cava and left kidney was performed without complications. Recognition of various venous anomalies, including double inferior vena cava, is important in the evaluation and surgical treatment of retroperitoneal disease. PMID- 8497996 TI - Extensive retroperitoneal mass. PMID- 8497997 TI - Role of detrusor instability in primary enuresis. AB - We studied 50 enuretic boys and girls by supine cystometry. Detrusor instability was found in 74 percent of the cases. The mean threshold volume at which detrusor instability was demonstrated was 200 mL. The mean bladder capacity of age-matched nonenuretic children was 325 mL. We consider detrusor instability at this reduced threshold volume to be the main cause of primary enuresis. PMID- 8497998 TI - Testicular torsion and its effects on contralateral testicle. AB - Twenty-six male adult Noble (Nb) rats underwent unilateral left testicular torsion of 720 degrees. The testicles of the 6 control animals were immediately detorsed. The experimental animals were divided into 4 groups according to the surgical approach (abdominal vs. scrotal) and location where the torsed testicle was placed (abdomen vs. scrotum). After six hours all torsed testicles in the experimental groups were detorsed. One month later all animals were sacrificed, and the contralateral testicles were examined for spermatogenesis and mean seminiferous tubular diameter. All groups displayed decreased spermatogenesis with smaller mean seminiferous tubular diameter as compared with the control group. PMID- 8497999 TI - New Cavitron system (CUSA/CEM): its application for kidney surgery. AB - A new Cavitron Ultrasonic Surgical Aspirator system (CUSA/CEM), which contains electrocautery function at the hand piece, was used for partial nephrectomies in dogs without clamping the renal artery. The advantages of this new device (CUSA/CEM) over the original CUSA are: (1) it enabled more precise resection of the tissue in a dry field, (2) shorter operating time, and eventually (3) helpful for reduction of blood loss. The microscopic examination of the resected kidney revealed minimal reaction and damage to the adjacent kidney tissue as compared with the effect by electrocautery or microwave tissue coagulator. PMID- 8498000 TI - Prune belly syndrome in adult man. PMID- 8498001 TI - Growth-induced haemodynamic changes in healthy Friesian calves. AB - This study investigated the pattern of growth-induced haemodynamic changes in normal calves during their first year of life. The central venous pressure (CVP), the right ventricular pressure (RVP), the pulmonary arterial pressure (PAP), the pulmonary capillary wedge pressure (PW), the systemic arterial pressure (SAP) and the cardiac output (CO) were measured in 41 healthy Friesian calves. The heart rate (HR), the stroke volume (SV), the cardiac and stroke indices (CI and SI, respectively), the pulmonary and systemic vascular resistance (PVR and SVR, respectively), the right ventricular and left ventricular work (RVW and LVW, respectively) and their corresponding indices (PVRI, SVRI, RVWI and LVWI, respectively) were also measured or calculated. The cardiac output, SV, SAP, PVRI, SVRI, RVW and LVW increased significantly while the HR, CI, PVR, SVR, RVWI and LVWI decreased significantly with somatic growth. The right-sided vascular pressures did not change significantly. The significant increase in systemic arterial pressure may be due to the simultaneous increase in CO. The high CI observed in the first few weeks of life was attributed to a high metabolic rate and might induce a reduced cardiac pumping reserve in young calves. In consequence, a therapeutic inotropic intervention may have little potential benefit at this age. PMID- 8498002 TI - Preliminary investigation of an ELISA kit as a qualitative assay for rabbit progesterone. AB - An ELISA kit for measuring plasma progesterone in bitches was investigated to determine its potential as an assay for rabbit progesterone. The results suggest that the kit can be used for the qualitative assessment of rabbit progesterone, either in plasma or whole blood. Pregnant and pseudopregnant rabbits can be differentiated accurately at day 19 which is reported to be the optimum time to remate pseudopregnant females. The fact that whole blood can be used instead of plasma offers considerable potential benefit to rabbit breeders. PMID- 8498003 TI - Use of ultrasound to diagnose testicular degeneration in a goat. AB - A seven-year-old infertile British alpine buck with small testes had bilateral testicular degeneration, as confirmed by the presence of a large number of dead and abnormal spermatozoa and a low percentage of progressively motile spermatozoa in its semen. Histopathological examination of the testes post mortem showed typical degenerative changes in the seminiferous tubules, with some tubules showing evidence of calcification. Ultrasonographically, the testicular parenchyma was uncharacteristically heterogeneous with an abundance of dense echogenic areas scattered through it. PMID- 8498004 TI - African horse sickness viruses isolated in Kenya. PMID- 8498005 TI - Testing for enzootic bovine leukosis. PMID- 8498006 TI - Bovine embryo transfer. PMID- 8498007 TI - Docking of dogs. PMID- 8498008 TI - Ovine iritis. PMID- 8498009 TI - Pharmacokinetics and bioavailability of doxycycline hyclate after oral administration in calves. AB - The bioavailability and pharmacokinetics of doxycycline hyclate were determined in calves with immature rumen function. The bioavailability of doxycycline after oral administration in a milk replacer was approximately 70%. The elimination half-life of doxycycline was found to be 9.5 +/- 3.0 h. after intravenous administration, and 12.6 +/- 5.0 h. after single oral administration. Plasma concentrations were determined after repeated oral administration of doxycycline dissolved in a milk replacer, at a dose of 5 mg per kg body weight, twice daily. During the period of administration, the plasma concentrations varied between Cmin of 1.0 +/- 0.19 mg/L and Cmax of 2.3 +/- 0.19 mg/L. PMID- 8498010 TI - The effect of rotational grazing for periods of one or two weeks on the build-up of lungworm and gastro-intestinal nematode infections in calves. AB - An experiment was carried out with three groups of grazing calves and one housed control group to study the effect of rotational grazing for periods of 1 and 2 weeks on the build up of lungworm and gastro-intestinal nematode infections respectively. The experiment demonstrated that rotational grazing for periods of 1 week on six plots prevented the build-up of heavy lungworm infections. A build up of heavier lungworm infections was observed in a group that was rotationally grazed for periods of 2 weeks on three plots and a group which remained on one plot throughout the grazing season; there was no difference between these two groups. In all three situations, there was an adequate development of immunity against D. viviparus, as measured by worm recovery after challenge infection at the end of the experiment in comparison with worm recovery of the similarly challenged control group. Neither rotational grazing scheme protected the calves against gastrointestinal helminthiasis, because tracer calves, which grazed for 4 days only in August or October, acquired infections which would have resulted in severe illness or even death if necropsy had been postponed for a week. PMID- 8498011 TI - The reappearance of eggs in faeces of horses after treatment with ivermectin. AB - The reappearance of nematode eggs in faeces after ivermectin treatment was studied in 104 horses on 10 farms during the stabling period. Faecal samples were taken at weekly intervals. Sampling was discontinued when the mean egg output per farm was > 10% of the pre-treatment egg output. This point was reached after 63 days, when the mean output of eggs had decreased to 70.3%. Before treatment, 95.9% of the cultured larvae were of the cyathostome type, the others belonged to Gyalocephalus capitatus, Strongylus vulgaris, S. edentatus, Oesophagodontus/Poteriostomum spp., Triodontophorus spp. and Trichostrongylus axei. After treatment, the cultures nearly always produced 100% cyathostome larvae, although occasionally low numbers (< 1%) of larvae of large strongyles (mainly S. edentatus, rarely S. vulgaris and Oesophagodontus spp.) and T. axei were seen. PMID- 8498012 TI - Review of health problems in group-housed sows, with special emphasis on lameness. AB - In the Netherlands, there is a trend towards housing gestating sows in groups. Vulva biting and lameness have been described as major health problems in group housed sows. Besides these problems, the effects of group housing on morbidity, reproduction parameters and the occurrence of infectious disease have been investigated. The literature is reviewed, with special emphasis on lameness. PMID- 8498013 TI - Cost-benefit analysis of a screening strategy for Salmonella enteritidis in poultry. AB - Salmonella enteritidis is an emerging problem in several industrial countries. Outbreaks caused by this organism are almost always associated with the consumption of eggs and egg-products originating from infected poultry flocks. To reduce human infection, elimination of contaminated flocks could be considered. In this study we estimated the effectiveness of such a measure to reduce human infections. If poultry flocks are screened for S. enteritidis only once during their laying period, there is a 43.7% reduction in contaminated eggs. The effectiveness increases if the frequency of screening is increased, resulting in a 65.4% reduction in contaminated eggs after three screenings. The costs of this intervention strategy are determined by both the costs of screening and the economic losses of destroying poultry flocks. PMID- 8498014 TI - Thrombocytopenia in lambs fed with bovine colostrum. AB - Artificially reared lambs, fed with bovine colostrum, died within 48 hours after birth, showing thrombocytopenia and extensive haemorrhages on autopsy. The mechanism behind was not fully understood, but experimental immunization of young cattle against sheep red blood cells, carried out five years earlier on the same farm, may have played a role. PMID- 8498015 TI - [Sanitary epidemiological surveillance during troop operations under extreme conditions]. PMID- 8498016 TI - [An analysis of the infectious morbidity in the troop personnel of a military district by using a personal computer]. PMID- 8498017 TI - [An improvement in the system of the staged treatment of the wounded with the wide use of air transport]. PMID- 8498018 TI - [The diagnostic potentials of magnetic resonance tomography in diseases of the spine and spinal cord]. PMID- 8498019 TI - [The indications and contraindications for laser therapy]. PMID- 8498020 TI - [The importance of the sanatorium stage of rehabilitation in the prevention of the late sequelae of viral hepatitis]. PMID- 8498021 TI - [The clinico-epidemiological efficacy of thymogen in acute respiratory viral infections in a military collective]. AB - This study gathers the results of epidemiological examination in training military unit, making evaluation of prophylactic efficiency of timogen, i.e. synthetic peptide of thymus for flu and other acute respiratory infections (ARI). The high clinico-epidemiological efficiency of timogen was proved in intranasal and subcutaneous administration that had led to a considerable reduction of morbidity rate, gravity and duration of ARI. Experimental substantiation for timogen administration was obtained that proved its efficiency for flu and other ARI prophylaxis in military units. PMID- 8498022 TI - [Angina morbidity in an organized collective with a periodic turnover of its personnel]. AB - The article studies the average angina morbidity in the military unit during 9 years which resulted in 48.4% (scarlet fever--0.34%). Laboratory diagnostics is needed to make the estimation of streptococcal infection which has an acute respiratory infectious character during its clinical course. Among the whole number of patients 89.2% have come through this illness for one time, 9% twice, and 4.8%--three times. The dynamics of the angina morbidity had a periodical cycle of 2-3 years which was independent from the morbidity cycle of local civilian population. The authors show a statistic dependency between average morbidity index and the quantity of servicemen in one dormitory, its square and volume per one man. Application of "time before illness" index for 24 months made it possible to disclose the phase character in the development of streptococcal infection among personnel of the same call-up period. The general tendency towards reduction of the morbidity index was accompanied with regular upgrades of the infection after each spring or autumn renovation of personnel. PMID- 8498023 TI - [A method for the accelerated determination of the virulence of Y. pestis cultures in the epizootiological examination of natural plague foci]. AB - The author proposes a method of accelerated virulence definition during epizootiological examination of plague causative agents. This method is based on studying the growth of Y. pestis culture in five media composed of standard components. The method was tested in the conditions of field mobile medical laboratory. PMID- 8498024 TI - [A new stage in the development of the regulation requirements for preserving and strengthening the health of servicemen]. PMID- 8498025 TI - [The concept of hygienic diagnosis at the current stage]. PMID- 8498026 TI - [From the experience of the sanitary epidemiological surveillance of the troops in the 14th Army]. PMID- 8498027 TI - [The diagnosis and prevention of unfavorable mental states in the flight personnel of ship-based aviation]. AB - An anonymous questionnaire was filled out by 126 pilots and navigators. The goals of this study were to disclose their "hard" mental states (subjective discomfort) and concrete factors that influenced upon psychosomatic and moral status during long cruise. The article gives the analysis of professional, psychological and welfare factors which may originate these states. The authors gained data which substantiated the prophylactic ways against unfavourable mental states in long cruise. PMID- 8498028 TI - [Pharmacological agents for maintaining the work capacity of flight personnel under extreme emotional stress]. PMID- 8498029 TI - [The function of the cardiovascular and immune systems of sailors during a cruise]. PMID- 8498030 TI - [Occupational medicine and military hygiene: the problems and the ways for their solution]. AB - From the point of view of occupational medicine the Army, Air Forces and Navy may be considered as a specific large-scale industrial branches which has some features in common with civilian branches. The authors propose to join the efforts of military and civilian hygienic science to solve the problems of ecology, sanitary standardization, adaptation and acclimatization in order to estimate and control the risk of professional pathology. The article shows basic trends of fundamental researches and scientific outlines for nearest and long term period. PMID- 8498031 TI - [Petr Andreevich Kupriianov--outstanding Soviet surgeon (on the centenary of his birth)]. PMID- 8498032 TI - [A. P. Dobroslavin and modern military hygiene]. PMID- 8498033 TI - [The Voenno-meditsinskii zhurnal of 1823]. PMID- 8498034 TI - [Born in days of war]. PMID- 8498035 TI - [The methodology for studying the health of servicemen]. PMID- 8498036 TI - [The ethics of the psychophysiologist]. PMID- 8498037 TI - [The use of laser technology in surgical practice]. PMID- 8498038 TI - [The prognosis and prevention of cardiac muscle ruptures in myocardial infarct]. AB - This article is based on the examination of 850 patients with acute transmural myocardial infarction, including 48 fatal cases in the result of external cardiac rupture. Immunological and biochemical indices of all patients have shown a high rate of necrotic processes in cardiac muscle in cases of heart rupture. The authors disclose the risk factors of cardiorrhexis and give recommendations for its prophylaxis. PMID- 8498039 TI - [The course of duodenal peptic ulcer in the participants in the cleanup of the aftereffects of the accident at the Chernobyl Atomic Electric Power Station]. AB - 80 liquidators of Chernobyl disaster with aggravation of duodenal ulcer were examined, as well as a control group of 70 patients. In the group of liquidators some characteristic features were disclosed, namely peculiarities in the state of abdominal mucosa and clinical course of the disease. These data were obtained in the results of hematological, immunological and biochemical researches. PMID- 8498040 TI - [The effect of low radiation doses on the evolution of chronic dystrophic processes in the cornea and of lens opacity]. PMID- 8498041 TI - [The characteristics of allergic diseases in people exposed to the factors of a radiation catastrophe]. AB - The article deals with peculiarities of allergic diseases (bronchial asthma, pre asthma, pollinosis) in patients who were exposed to the factors of radiative, catastrophe. Screening--questionnaire was made on 381 patients who went through the Chernobyl disaster. 46 patients from this number who had various allergic diseases were chosen for specific diagnostics and immunological researches. A conclusion was made that critical systems of organism, and especially the immune systems had the major significance for the development and outcome of radiative injuries. The disorders in these systems contribute to the development of allergic diseases. PMID- 8498042 TI - [The use of the dental composite SK-M in the combined treatment of periodontal diseases]. PMID- 8498043 TI - [The clinico-diagnostic significance of tumor markers in malignant neoplasms]. PMID- 8498044 TI - [The clinical characteristics of parotid viral infection in adults]. AB - The article analyses the clinical course of parotid virus infection in 207 servicemen basicly from the scene of epidemic outbreaks. The period of disclosure of illness and further hospitalization of patients was considerably rapid. The diagnosis was frequently impeded by polymorphism of clinical features of illness and resulted in 25.8% of errors which enveloped localization of pathological process and the gravity estimation of the infection. Error diagnoses were also provoked by frequent appearance of slight and obscure forms of illness. The article stresses that unfavourable cases of parotid virus infection are no longer exceptional in the modern conditions. PMID- 8498045 TI - [Chlamydial infections (a review of the literature)]. PMID- 8498046 TI - [The organization of the hygienic expertise of food products in military epidemiological health establishments]. PMID- 8498047 TI - [The organizational aspects of treating minor wounds in modern war (1)]. AB - Loss replacement for the Armed Forces and national economy is considered to be the most complicated and actual problem in the conditions of NBC warfare. On the basis of the analysis of the 2nd World War and local conflicts over the past decade the authors came to a conclusion that precisely minor wounded, as well as minor ill and injured would be the basic source for recouping medical and irretrievable combat losses in active army. The article analyses the possible aspects of stage-by-stage rehabilitation of minimally wounded in the conditions of modern war, and proposes ways for their rapid return to the ranks. PMID- 8498048 TI - [The radiation hygiene problems of deactivating atomic power units]. PMID- 8498049 TI - [The toxicological safety of the personnel in fires on board naval ships]. PMID- 8498050 TI - [The etiopathogenetic characteristics of a decrease in hearing in flight personnel]. PMID- 8498051 TI - [A modified method of studying gastric secretion in aviation medical expertise]. PMID- 8498052 TI - [A holding clamp for the F-03 attachment for ultraviolet irradiation of the ENT organs and a bracket for the OKN-11-M mercury-quartz irradiator]. PMID- 8498053 TI - [A support for under the upper extremity for skeletal traction]. PMID- 8498055 TI - [Medical support for the Soviet troops in the Berlin Operation]. PMID- 8498054 TI - [A device for gastric intubation]. PMID- 8498056 TI - [The work organization problems of the hospital bases in the transfer areas in the war years]. PMID- 8498057 TI - [The problems of combat pathology and protection from weapons of mass destruction in the pages of the Voenno-meditsinskii zhurnal (on the 170th anniversary of Voenno-meditsinskii zhurnal)]. PMID- 8498058 TI - [N. L. Bidloo--the first teacher of surgery in Russia]. PMID- 8498059 TI - [The 50th anniversary of the Faculty of the Command Medical Staff of the S. M. Kirov Military Medical Academy]. PMID- 8498060 TI - [Should the physical development of servicemen be evaluated?]. PMID- 8498061 TI - [The cooperative effect of hydrocortisone, adrenaline, and high density lipoproteins in regulating the activity of multiple forms of liver hexokinase]. AB - High density lipoproteins (HDL) were shown to modulate the effect of hydrocortisone and adrenaline on activity of hexokinase in surviving liver tissue slices. The hormones inhibited the enzymatic activity while in presence of HDL the hormones exhibited an opposite effect. The phenomenon observed was termed a "cooperative effect"; it could not be reproduced by any single components of the system studied. Mechanism of the effect involved induction of all the multiple hexokinase forms which was abolished by actinomycin D. A specific function could be ascribed only to HDL3; HDL2, low and very low density lipoproteins did not exhibit any effects. The cooperative effect of HDL and of the adaptive hormones was also inhibited in the surviving liver tissue slices by vinblastine, gordox and methylamine thus demonstrating the sophisticated nature of the mechanism. PMID- 8498062 TI - [Change in insulin level in thermal and combined radiation-thermal injuries and insulin-modulating effect of the activity of middle molecular weight peptides in blood]. AB - Experimental and clinical studies demonstrated the occurrence of insulin resistance within the initial period of burns and combined radiation-thermal impairment as well as during the burns produced toxemia. Blood medium-weight molecular peptides may be essential in the regulation of insulin content as they exhibited a high affinity for insulin antiserum and were able to cause competitive interaction with insulin for the receptor sites of cell membranes. PMID- 8498063 TI - [Plasminogen activators and their function]. PMID- 8498064 TI - [Prophylactic effect of vitamin A, neutralizing the development of experimental insulin-dependent diabetes in animals]. AB - Vitamin A deficiency contributed to higher incidence of abnormalities in experimental animals with insulin-dependent diabetes induced by alloxan. However, the similar doses of alloxan did not cause diabetes in the animals maintained on a diet containing adequate amounts of vitamin A used for prophylactic purposes for a long time. The natural diabetogenic factor specific to insulin-dependent diabetes was not found in the blood serum of these animals. PMID- 8498065 TI - [Assessment of the activity of choline acetyltransferase in heart tissues]. AB - A procedure is described for the radioisotope assay of acetylcholine transferase activity (EC 2.3.1.6), which involved specific synthesis of acetylcholine in vivo. Bromine acetylcholine was used as an inhibitor of the enzyme; 14C-AcCoA was used as a substrate and product of the enzymatic reaction. 14C-acetylcholine was separated from the substrate by means of anion exchange chromatography. The procedure described was 5 times more sensitive than the methods developed by F. Fonnum (1975) and S. Tucek (1983) being similarly reproducible. The assay was tested in experiments with rats under various conditions of hyperbaric oxygenation, in simulation of myocardial infarction as well as in moderate immobilization stress. The findings suggest that estimation of the acetylcholine transferase activity may be involved in complex evaluation of the cholinergic system state in tissues, which is essential for the study of pathogenesis of their dysfunctions and development of respective approaches to eliminate these impairments. PMID- 8498066 TI - [Activity of proteolytic enzymes and their inhibitors in experimental myocardial ischemia]. AB - Proteolytic activity and activity of endogenous inhibitors of endopeptidases (using chymotrypsin and papain) were studied in the myocardium of rats with experimental ischemia during an acute phase (60 min) and within 5 days after ligation of the left descending coronary artery; effects of the beta adrenoblocking agent propranolol and the calcium antagonist verapamil on these activities was also studied. During the acute phase of ischemia, the activity of acid proteases was increased by 30%, that of Ca(2+)-activated neutral proteases by 15-20%. At the same time, the activity of serine proteases inhibitors was decreased while the activity of thiol protease inhibitors was increased. Within 5 days of coronary artery occlusion, Lysosomal thiol-dependent endopeptidases were activated in the myocardium; a considerably higher activity of the inhibitors of serine- and cysteine-containing endopeptidases was detected. The cardioactive drugs propranolol and verapamil affected selectively both endopeptidase activity and their inhibitors. PMID- 8498067 TI - [Lipid fractions of rat liver upon administration of ethanol and ethanolamine]. AB - After a single intragastric administration of 25% ethanol in a dose of 1 g/kg of body mass content of total lipids, lysophosphatidyl choline, phosphatidyl ethanolamine and cardiolipin was increased while phosphatidyl choline was decreased in the rat liver tissue. At the same time, there was a decrease in the rate of 2- 14C-acetate incorporation into esters of cholesterol, total phospholipids, lysophosphatidyl choline, sphingomyelin, phosphatidyl ethanolamine and cardiolipin. Administration of ethanolamine simultaneously with ethanol contributed to normalization of the lipid spectrum, impaired by the single ethanol inoculation. PMID- 8498068 TI - [Effect of 6-methyluracil on various indicators of the lipid peroxidation regulation system in the body]. AB - Single intraperitoneal administration of 6-methyluracil in a dose of 50 mg/kg was shown to affect some patterns of the physico-chemical system regulating lipid peroxidation in mice liver tissue and erythrocytes: antioxidative activity of lipids (AOA), composition of phospholipids; the drug altered also activities of superoxide dismutase and catalase in liver tissue and blood serum of rats. These alterations observed had phase expressed dynamics and their rate was dissimilar in various tissues and depended on the interval after drug administration. 6 Methyluracil exhibited the highest effect on the rate of AOA in liver tissue and on phospholipid composition in erythrocytes. The biological activity of the drug appears related to its effects on the system regulating lipid peroxidation. PMID- 8498069 TI - [The effect of exogenous lipids on the functional activity of the liver in experimental hepatitis]. AB - Content of lipids in blood serum and membranes of liver tissue endoplasmic reticulum, functional activity of microsomes, antitoxic activity of liver tissue as well as collagen production in rat liver tissue were studied in experimental hepatitis after administration of exogenous lipids (equine erythrocyte phospholipids and ganglioside GM3, bovine spinal cord phospholipids). All the preparations studied inhibited the functional activity of the liver cells which was expressed as a decrease of the lipids content in the microsomes, inhibition of glucose-6-phosphate dehydrogenase activity and impairment of the liver tissue antitoxic functions. Distinct inhibition of these reactions caused an increase of the collagen content in the liver tissue. PMID- 8498070 TI - [Comparative physico-chemical study of L-lysine-alpha-oxidase from surface and fermenter growth Trichoderma sp]. AB - Homogeneous preparations of L-lysine-alpha-oxidase were obtained from Trichoderma sp cultivated by using a surface technique and a fermenter set. The homogeneous enzyme preparations were similar in molecular mass, isoelectric point and substrate specificity. There was the single difference in the absorbance spectra, which may occur due to the presence of cofactor FAD in various oxidation states. The findings suggest that cultivation of Trichoderma sp in the fermenter set did not alter properties of L-lysine-alpha-oxidase produced. PMID- 8498071 TI - [Change in plasma fatty acid level in experimental mild craniocerebral injury]. AB - Content of fatty acids was studied in the blood plasma of rabbits in dynamics of experimental mild craniocerebral injury using gas-liquid chromatography. The content of all the fatty acids studied was markedly increased within the initial periods; then it was decreased down to control values within 2 hrs with the subsequent repeated increase. All these alterations appear to be compensatory body's reactions to the trauma. PMID- 8498072 TI - [Level of certain carbohydrate components in blood serum and urine of patients stomach and duodenal ulcer patients in the late post-vagotomy period]. AB - Estimation of protein-bound hexoses, fucose and sialic acids in the blood and urine of 64 patients with gastroduodenal ulcers within later periods after various types of gastric vagotomy showed that the denervation inhibited the protective barrier of gastric and duodenal mucosal membrane. Protective functions of gastroduodenal mucosal membrane were most distinctly inhibited after selective proximal vagotomy which may be responsible for higher amounts of recurrences of ulcerous disease after this type of vagotomy than other types of denervation. PMID- 8498073 TI - [Status of nucleoprotein synthesis in hematopoietic organs in mice with primary hypothyroidism]. AB - A rate of incorporation of 3H-thymidine, 3H-uridine and 14C-glycine into the nucleoproteins of bone marrow, spleen, thymus and ileocecal lymph nodes was studied in BALB/c mice with hypothyrosis developed after administration of 1% KClO4 within a month. Distinct hypoplasia of bone marrow and spleen was found in the experimental animals; the synthesis of nucleoproteins was most impaired in bone marrow. The dependence of hemopoietic tissues on thyroid hormones was decreased as follows: bone marrow > spleen > thymus > lymph node. After subcutaneous administration of triiodothyronine (T3) in a dose of 50 mg/kg daily within 3 days of synthesis of nucleoproteins was considerably stimulated and the amount of cells was increased in bone marrow and spleen. Less distinct stimulating effect of T3 was observed in the thymus and lymph nodes of these animals. PMID- 8498074 TI - Induction of 7-ethoxyresorufin-O-deethylase (EROD) activity in mice foetuses by the PCB-congener 3,3',4,4'-tetrachlorobiphenyl. AB - 1. 3,3',4,4'-Tetrachlorobiphenyl (TCB) induces liver microsomal 7-ethoxyresorufin O-deethylase (EROD) activity, and this P450 isoform, i.e. CYP 1, is involved in the metabolism of TCB. 2. TCB administered i.p. to pregnant mice (5-25 mg/kg) induced foetal as well as maternal hepatic EROD activity; in all cases the maternal induced activity was higher than the foetal activity. EROD activity of TCB-induced foetuses increased with developmental age, but decreased with the length of time after treatment. 3. Strain differences were seen; in control mice and TCB-treated dams NMRI > C57BL in EROD activity, but in transplacentally TCB treated foetuses, C57BL > NMRI. EROD activity in non-pregnant control C57BL mice was higher than in pregnant ones, whereas no activity was seen in control foetuses. 4. Results indicate that TCB at a certain dose can induce foetal metabolism, but that earlier observed foetal accumulation at lower TCB doses is probably a consequence of transplacental transport of maternally-produced metabolites. PMID- 8498075 TI - Stereoselectivity of iododoxorubicin reduction in various animal species and humans. AB - 1. The excretion of iododoxorubicin in urine as the 13-dihydro derivative, iododoxorubicinol, is much greater in man than in rat, dog, rabbit and monkey. Iododoxorubicinol epimers in urine from man and the animal species after i.v. administration of iododoxorubicin, were quantified by h.p.l.c. 2. (13R) Iododoxorubicinol was not detectable in rat, dog and human urine and accounted for no more than 0.15% dose in urine of 1/3 rabbits and 3/3 monkeys. (13S) Iododoxorubicinol in human urine amounted to 5.6% dose, whereas in rat only 0.01% dose and in monkey only 0.91% dose was found. 3. As for idarubicin, the in vivo reduction of iododoxorubicin is highly stereoselective, giving the (13S)-epimer almost exclusively. Erythrocyte ketone reductases may account for the higher formation of (13S)-iododoxorubicinol in man. PMID- 8498076 TI - Intestinal transformation of 2,6-dinitrotoluene in male Wistar rats. AB - 1. Metabolites formed by anaerobic incubation of 2,6-dinitrotoluene (2,6-DNT) with intestinal microflora of male Wistar rats were examined. Intestinal transformation of 2,4-dinitrotoluene (2,4-DNT) was also studied to determine whether azoxy compounds are produced in the anaerobic incubation. 2. 2,6-DNT was transformed by the intestinal microflora into 2-nitroso-, 2-hydroxylamino- and 2 amino-6-nitrotoluene, and 2,6-diaminotoluene. A time course study showed that 2 nitroso-, 2-hydroxylamino-, and 2-amino-6-nitrotoluene reached peaks at 2, 5 and 6 h of the anaerobic incubation; 2,6-diaminotoluene appeared at 12 h of the incubation. The formation of 2,6-diaminotoluene from 2-amino-6-nitrotoluene in the incubation was confirmed. 3. Two nitroazoxy compounds, namely, 2,2'-dimethyl 5,5'-dinitroazoxybenzene and 4,4'-dimethyl-3,3'-dinitroazoxybenzene, in addition to known metabolites (nitrosonitrotoluenes, hydroxylaminonitrotoluenes, aminonitrotoluenes and diaminotoluene), were detected in the incubation of 2,4 DNT with intestinal microflora. The formation of the two nitroazoxy compounds (2% dose in 24 h) was non-enzymic and merely involved mixing 2-hydroxylamino-4 nitrotoluene with 2-nitroso-4-nitrotoluene or 4-hydroxylamino-2-nitrotoluene with 4-nitroso-2-nitrotoluene in methanol, respectively. PMID- 8498077 TI - Peroxidation of the antimalarial drug primaquine: characterization of a benzidine like metabolite with methaemoglobin-forming activity. AB - 1. An organic solvent-extractable product was obtained from incubations of primaquine (70 mM) with H2O2 (70mM) and horseradish peroxidase (0.5 mg/ml) in acetate buffer, pH4.2. 2. The metabolite was characterized as 5,5-di-(8-[(4-amino 1-methylbutyl)amino]-6-methoxyquinoline) by 1H-n.m.r., mass, FT-i.r. and u.v. visible spectroscopy. 3. Incubations of rat erythrocytes with 5,5-di-(8-[(4-amino 1-methylbutyl)amino]-6-methoxyquinoline) led to the formation of methaemoglobin in a time- and metabolite concentration-dependent manner. PMID- 8498078 TI - Dependence of glycine conjugation on availability of glycine: role of the glycine cleavage system. AB - 1. Glycine conjugation of benzoic acid was investigated in anaesthetized rats by measuring the disappearance of benzoate from blood, and the appearance of benzoylglycine in blood and urine. 2. Administration of glycine (1-10 mmol/kg,i.v.) increased the capacity of benzoylglycine formation in a dose dependent fashion, with a maximal rate (8.1 mumol/kg per min) occurring after administration of 5 mmol/kg glycine. The normal endogenous glycine supply (1.7 mM in liver) permits glycine conjugation only at an approximate half-maximal rate (4.5 mumol/kg/per min). 3. The increase in benzoylglycine formation in response to exogenous glycine supply is also a function of the benzoate dosage. Decreased responsiveness at high benzoate dosage indicates that the availability of coenzyme A is another factor that also limits the capacity of glycine conjugation. 4. Cysteamine (200 mg/kg, i.p.), a potent inhibitor of the mitochondrial glycine cleavage system, rapidly increased hepatic glycine concentration 2-3-fold without affecting the concentration of the other co substrates (i.e. coenzyme A and ATP) of glycine conjugation. 5. Administration of cysteamine increased the blood clearance of benzoate by 50%, the appearance of benzoylglycine in blood, and the urinary excretion of benzoylglycine. 6. It is concluded that the activity of glycine cleavage system is an important determinant of glycine supply and, thereby, the capacity of glycine conjugation of xenobiotics. PMID- 8498079 TI - In vitro oxygenation of N,N'-diphenylguanidines. AB - 1. The enzymic C-oxygenation of N,N'-diphenylguanidine (DPG) to N-(4 hydroxyphenyl)-N'-phenylguanidine (4HPG) and the N-oxygenation of N,N'-bis (pentafluorophenyl)-guanidine (BPG) to N"-hydroxy-N,N"-bis-(pentafluorophenyl) guanidine (HBPG) is reported. 2. The metabolites were identified by t.l.c. and mass spectral analysis using synthetic reference compounds. 3. Rat and rabbit liver homogenates (9000 g supernatant and microsomes) were used as enzyme source. 4. The enzymic oxygenations were both O2 and NADPH dependent. NADPH could not be replaced by hydrogen peroxide. 5. 15N-n.m.r. spectroscopy was used to elucidate structure and tautomerism of BPG and HBPG. PMID- 8498080 TI - Effect of treatment with pyrazine and some derivatives on cytochrome P450 and some enzyme activities in rat liver. AB - 1. The effect of pyrazine and three pyrazine derivatives, namely (methylthio) methylpyrazine (MTMP), 5, 6, 7, 8-tetrahydroquinoxaline (CHP) and 5-methyl-6, 7 dihydro-5'-cyclopentapyrazine (CPP), on hepatic peroxisomal and microsomal enzyme activities have been studied in male Sprague-Dawley rats. MTMP (0.25-2 mmol/kg per day) and the other compounds (1 mmol/kg/day) were administered by i.p. injections for 3 days. 2. None of the test compounds appeared to be peroxisome proliferators as there was no marked effect on hepatic palmitoyl-CoA oxidation, and neither pyrazine nor MTMP induced microsomal lauric acid 12-hydroxylase. 3. In contrast, all four compounds induced hepatic microsomal cytochrome P450 dependent enzyme activities. MTMP induced the metabolism of several mixed function oxidase substrates including, 7-pentoxyresorufin, 7-benzoxyresorufin, benzphetamine, 4-nitrophenol and aniline, whereas pyrazine induced the metabolism of fewer substrates but including 4-nitrophenol and aniline. 4. By Western immunoblotting MTMP was found to increase levels of CYP2B1 and CYP3A isoenzymes, whereas pyrazine increased CYP2E1. 5. Thus, while pyrazine appears to be mainly a CYP2E inducer, MTMP is a mixed inducer of cytochrome P450 isoenzymes in the CYP2B, CYP3A and CYP2E subfamilies. CPP is probably a CYP2E inducer in rat liver, whereas CHP appears to be a mixed inducer of cytochrome P450 isoenzymes in the CYP2B, CYP3A and CYP2E subfamilies. PMID- 8498081 TI - Determination of antipyrine sulphoconjugates in isolated cultured rat hepatocytes. AB - 1. An analytical method for the simultaneous determination of three major metabolites of antipyrine, namely, 3-hydroxymethylantipyrine (phase I), 4 hydroxyantipyrine sulphoconjugate (phase II) and norantipyrine sulphoconjugate (phase II) in cultured rat hepatocytes has been developed and applied to the study of induction or inhibition of these metabolic pathways following pretreatment of rats with several inducers or inhibitors. 2. Phenobarbital was the most effective inducer of the three pathways studied, particularly the formation of 4-hydroxyantipyrine sulphoconjugate; 3-methyl-cholanthrene (MC) increased the formation of the two sulphoconjugates, but decreased the formation of 3-hydroxymethylantipyrine. 3. Rifampicin inhibits antipyrine metabolism in rat. The three metabolic pathways studied were decreased by 30%. 4. SKF 525A markedly inhibited the three metabolic pathways; piperonyl butoxide and omeprazole decreased the three pathways but to a lesser extent. Cimetidine decreased the two sulphoconjugates pathways, but did not affect 3 hydroxymethylantipyrine formation. PMID- 8498082 TI - Liver NADPH-dependent oxidation of the 5-nitrofurans, FANFT and ANFT, by guinea pig and rat. AB - 1. Oxidative metabolism of the bladder carcinogens FANFT/ANFT was examined in vitro in guinea pig (resistant species) relative to rat (susceptible species). 2. The total rate of ANFT hepatic metabolism by guinea pig (soluble metabolites plus protein bound, 354 pmol/min per mg protein) was approx. 4 times that in rat. 3. The total rate of FANFT metabolism was similar in both species and approx. one quarter that for ANFT in guinea pig. In rat, the rate of total metabolism of FANFT and ANFT was similar. 4. Cytochrome P450 inhibitors, 2,4-dichloro-6 phenylphenoxyethylamine, 7,8-benzoflavone, and n-octylamine largely inhibited metabolism in guinea pig, but had little effect in rat. 5. H.p.l.c. analysis of ANFT metabolites indicated distinctly different products in guinea pig compared to rat. 7,8-Benzoflavone decreased metabolite formation by 80% in guinea pig, but only 30% in rat. 6. Flavin-dependent monooxygenases may participate in metabolism of these carcinogens in rat, but not guinea pig. 7. Because ANFT is thought to be a more proximate carcinogen than FANFT, the increased rate of ANFT metabolism and the formation of different products in guinea pig compared to rat may partially explain the resistance of guinea pig to FANFT-induced bladder cancer. PMID- 8498083 TI - Effects of diethyl maleate on phenyl-hydroquinone-induced cytotoxicity in isolated rat hepatocytes. AB - 1. The effects of diethyl maleate (DEM) on the cytotoxicity of phenyl hydroquinone (PHQ) and other hydroquinones were studied in freshly isolated rat hepatocytes. 2. Addition of PHQ (0.5 or 0.75 mM) to hepatocytes resulted in dose dependent cell death accompanied by the abrupt depletion of both GSH and protein thiols and the accumulation of phenyl-benzoquinone (PBQ). 3. Pretreatment with DEM (1.25 mM), which causes an abrupt depletion of cellular GSH in hepatocytes, delayed the onset of PHQ-induced cytotoxicity. The delay correlated with inhibition of PBQ formation. 4. Although the pH of the cell suspension was increased slightly (mean pH 0.18) by incubation under carbogen flow, the addition of DEM to the cell suspension inhibited both the increase in pH and the formation of PBQ from PHQ. 5. In hepatocyte suspensions without DEM, PHQ cytotoxicity was dependent on pH, and toxicity was associated with oxidation of PHQ and accumulation of PBQ. 6. Among other hydroquinones (0.5 mM), tert-butyl hydroquinone-induced cytotoxicity was decreased by DEM (1.25 mM), but DEM did not affect the cytotoxicity of 2,5-di(tert-butyl)-1,4-benzohydroquinone. 7. PHQ induced cytotoxicity correlated with the accumulation of PBQ in the cell, and the inhibition of PHQ-induced cytotoxicity by DEM correlated with pH-dependent changes in PBQ formation. PMID- 8498084 TI - Metabolism and disposition of phenazopyridine in rat. AB - 1. The blood profile, tissue distribution, biliary and urinary excretion, and metabolism of 14C-phenazopyridine (PAP) was studied in male Wistar rats. 2. Based on the blood profile of 14C the absorption of PAP from the gastrointestinal tract was rapid; the t1/2 of elimination was 7.35 h. 3. Biliary excretion was a major route of elimination with 40.7% dose excreted by this route in bile duct cannulated rats over the 0-8 h period. The predominant metabolite was conjugated 4'-hydroxy-PAP. 4. Liver and kidney showed the highest tissue levels of PAP derived 14C, and significant covalent binding was found in these two tissues. 5. The major urinary metabolite of PAP was 4-acetylaminophenol (NAPA) followed in order by 5,4'-dihydroxy-PAP, 5-hydroxy-PAP, 4'-hydroxy-PAP and 2'-hydroxy-PAP; unchanged PAP accounted for < 1% dose. 6. Doubling the dose of PAP to 200 mg/kg caused a proportionate decrease in urinary NAPA excretion and an increase in 5 hydroxy-PAP. PMID- 8498085 TI - Phenytoin induction of cytochrome P4502B in mice: effects on hexobarbital hydroxylase activity. AB - 1. Treatment of ICR and C57BL/6 mice with phenytoin (50 mg/kg, i.p., 3 days) resulted in approximately 33 and 43% increases in hepatic cytochrome P450 levels relative to uninduced microsomes, respectively. Phenytoin treatment caused a 63% decrease in hexobarbital sleeping time in ICR mice (19 versus 52 min). 2. Both Western immunoblot analysis and solid phase radioimmunoassay using monoclonal anti-rat P4502B antibody showed that P4502B was increased significantly in phenytoin-induced mouse microsomes compared with uninduced mice. P4502B9 was the predominantly induced form whereas 2B10 was elevated marginally. Phenytoin was as efficacious as phenobarbital in increasing P4502B. 3. Phenytoin treatment resulted in an approximately 8-fold increase in hexobarbital hydroxylase activity whereas phenobarbital treatment caused an approximately 13-fold increase. Addition of anti-P4502B antibody produced complete inhibition of hexobarbital oxidation in phenytoin-induced microsomes, indicating that raised P4502B in phenytoin-induced microsomes is associated with the increased hexobarbital hydroxylase activity. 4. Phenytoin failed to increase P4501A in either C57BL/6 or ICR mice, as assessed by both immunoblot analysis and metabolic activities. Although both aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase activities were raised approximately two-fold following phenytoin treatment, the metabolic activities were not inhibited by anti-P4501A antibody. 5. These results provide evidence that phenytoin induces P4502B in mice with pronounced increase in hexobarbital hydroxylase activity, and fails to induce P4501A in either C57BL/6 or ICR mice. PMID- 8498086 TI - Lipid peroxidation-cytochrome P450 interactions. Use of linoleic acid hydroperoxide in the characterization of the spin-state of membrane-bound P450. AB - 1. A procedure (linolenic acid hydroperoxide (LAHP) deletion method) is described in which LAHP is added to the reference cuvette of a pair of spectrally balanced cuvettes containing hepatic microsomes to produce a composite high spin (HS)-low spin (LS)-spectrum of P450. 2. The LAHP deletion method was used to determine the spin state of P450 in rat hepatic microsomes with and without the addition of type I compounds. 3. Advantage was taken of the temperature dependency of the spin state of P450 to determine the overall enthalpic and entropic changes for the spin equilibrium to generate computer-derived spectra of HS and LS forms of P450, and to construct a nomogram that allows direct estimation of the percentage of HS and LS spin forms of P450 in intact microsomes at temperatures compatible with biochemical functions. 4. The h.p.l.c. deletion method was used to demonstrate that HS-P450 comprised 57% of the P450 in hepatic microsomes; addition of type I substrates to these microsomes raised the level of HS-P450 to 97%. 5. The percentage of HS-P450 generated by the addition of type I compounds to microsomes declined with increasing deletions of P450 until at the extrapolated 100% level of deletion there was no HS-P450 above that of the original 57% observed in the absence of added compounds. This can be explained if LAHP destroys part of the LS-P450 while altering the remaining LS-P450 such that it retains its LS spectral characteristics but loses its capacity to form HS P450 when type I substrates are added. 6. These studies support the concept that about 50% of hepatic microsomal P450 is functionally in the HS state due to binding with high affinity endogenous substrates or other membrane components; the remaining P450 is LS-P450 that can bind to exogenous substrates to form HS-P450. 7. Applications of the LAHP deletion method for assessment of catalytic properties of membrane-bound P450 at ambient temperatures are discussed. PMID- 8498087 TI - Metabolism of 2-acetylaminofluorene. I. Metabolism in vitro of 2 acetylaminofluorene and 2-acetylaminofluoren-9-one by hepatic enzymes. AB - 1. 2-Acetylaminofluorene (AAF) was converted by rat liver microsomal and cytosolic enzymes to 2-aminofluorene (AF), 2-glycoloylaminofluorene (GAF), 2 acetylaminofluoren-3-, -7-, and -9-ol (3-, 7-, 9-hydroxy-AAF), and 2 acetylaminofluoren-9-one (AAF-9-one). In addition, a new metabolite MX1 was detected. 2. AAF was converted by rabbit liver microsomal and cytosolic enzymes to N-hydroxy-AAF, GAF, 5-, 7-, and 9-hydroxy-AAF, AAF-9-one, 5- and 7-hydroxy-AAF 9-one (new compounds), and AF, indicating species differences in the N- and ring hydroxylation of AAF and secondary oxygenation of AAF. In addition, an unknown metabolite MX2 was detected. 3. AAF-9-one was converted by rat liver microsomal and cytosolic enzymes to optically active 9-hydroxy-AAF and 7-hydroxy-AAF-9-one; in addition MX1 was found. 4. Rabbit liver microsomal and cytosolic enzymes converted AAF-9-one to 2-aminofluoren-9-one (AF-9-one), 9-hydroxy-AAF, N-hydroxy AAF-9-one, GAF-9-one, 7-hydroxy-AAF-9-one, and 7,9-dihydroxy-AAF. In addition, metabolite MX1 and its dihydro-dihydroxy derivative were found. 5. These results indicate that AAF and AAF-9-one have common metabolic pathways, as AAF after primary oxygenation to 9-hydroxy-AAF and partial dehydrogenation to AAF-9-one, undergoes secondary oxygenation to 7-hydroxy-AAF-one and MX1 as well as the corresponding dihydro-dihydroxy derivatives. PMID- 8498088 TI - Evidence for tangeretin O-demethylation by rat and human liver microsomes. AB - 1. Tangeretin, a polymethoxylated flavone, was studied as a substrate for cytochrome P450-catalysed demethylation reactions by rat and human liver microsomes. Evidence has been presented for the production of formaldehyde in the presence of tangeretin and NAD(P)H. Kinetic studies showed a Km value for tangeretin of about 18 microM in both species. 2. The reaction was inhibited by CO, piperonyl butoxide, 7,8-benzoflavone, propyl gallate, aminobenzothiazole and metyrapone. 3. Rats pretreated with classical cytochrome P450 inducers (Aroclor 1254, 3-methylcholanthrene, phenobarbital, dexamethasone and ciprofibrate) or with flavonoids (flavone, flavanone, quercetin and tangeretin) resulted in increased microsomal demethylation of tangeretin after 3-methylcholanthrene and flavone only. Tangeretin did not enhance its own metabolism. 4. Tangeretin interacted with the oxidized form of cytochrome P450 to produce a reverse type I spectrum. 5. Results indicate that tangeretin is metabolized in liver microsomes by an O-demethylation reaction involving cytochrome P450. PMID- 8498089 TI - Selective induction of rat liver phase II enzymes by N-heterocycle analogues of phenanthrene: a response exhibiting high correlation between UDP glucuronosyltransferase and microsomal epoxide hydrolase activities. AB - 1. Among nitrogen heterocycles based on the planar phenanthrene structure are three (1,7- and 4,7-phenanthroline and phenanthridine) which selectively increase rat hepatic phase II drug metabolizing enzyme activities without increasing cytochrome P450 concentration. Of six monooxygenase activities investigated, only ethoxyresorufin dealkylase was raised but this was only minor. 2. The detergent activated UDP-glucuronosyltransferase activities towards morphine, 4-nitrophenol, and 1-naphthol were increased up to five-, three- and two-fold of control respectively. Microsomal epoxide hydrolase activity towards cis-stilbene oxide was increased up to three-fold and cytosolic glutathione S-transferase activity towards 1-chloro-2, 4-dinitrobenzene reached twice the control value. 3. Cytosolic 4-nitrophenol sulphotransferase activity was not increased by any compound and like some monooxygenase reactions, was decreased by 4,7- and 1,7 phenanthrolines. 4. 1,10-Phenanthroline and two compounds which lack a heterocyclic nitrogen atom, (phenanthrene and 9-phenanthrol), failed to elicit any induction of enzyme activities. 5. Changes in microsomal epoxide hydrolase activity showed high correlation (r = 0.97) with changes in UDP glucuronosyltransferase (4-nitrophenol) activity. PMID- 8498090 TI - p-Nitrophenylacetate hydrolysis by honey bee esterases: kinetics and inhibition. AB - 1. The kinetics and inhibition of p-nitrophenylacetate hydrolysis by cytosolic esterases of 1-day old female honey bees, Apis mellifera L., were studied. 2. The calculated values obtained were Km = 2.27 x 10(-5)M and Vmax = 2.48 x 10(-8) mol/s per mg protein. 3. The inhibition mechanisms examined for four organophosphorus insecticides were highly competitive in nature and based on competitive inhibition coefficients the order of toxicity was naled > dichlorvos > cis-mevinphos = trans-mevinphos. 4. Comparisons are made with the alfalfa leafcutting bee, Megachile rotundata (Fab). PMID- 8498091 TI - Comparative sulphoxidation of albendazole by sheep and cattle liver microsomes and the inhibitory effect of methimazole. AB - 1. The comparative rates of oxidation of the benzimidazole anthelmintic, albendazole (ABZ), by sheep and cattle liver microsomes, and inhibition by the antithyroid compound methimazole (MTZ) were investigated. 2. ABZ was oxidized to its sulphoxide metabolite (ABZSO) in an NADPH concentration-dependent reaction. Heat inactivation of the microsomal flavin-containing mono-oxygenase system significantly decreased the NADPH consumption of microsomes in the presence of ABZ, MTZ and thiourea. 3. Oxidation of ABZ, MTZ and thiourea by sheep liver microsomes consumed significantly more NADPH than oxidation by cattle microsomes. 4. Neither the pro-ABZ drug, netobimin, nor the ABZ sulphone metabolite (ABZSO2) was modified by incubation with either sheep or cattle liver microsomes. 5. ABZSO was oxidized into ABZSO2 at a very slow rate and only when a high microsomal protein concentration was used. 6. MTZ was a potent inhibitor of ABZ sulphoxidation and the inhibition was significantly lower in cattle than in sheep microsomes. PMID- 8498092 TI - Propachlor-S-cysteine: a major circulating metabolite in the calf, pig and rat after administration of propachlor. AB - 1. Propachlor-S-cysteine was the major metabolite found in systemic blood from rat, pig and calf given propachlor via the stomach. It was also the major metabolite found in the portal blood of pig; the portal blood of rat and calf was not examined. 2. Erythrocytes were the major transporter of propachlor metabolites in rat blood whereas plasma was the major transporter of these metabolites in pig and calf. 3. There was no evidence for metabolism of propachlor-S-cysteine by rat blood or by cytosol from rat, pig and calf erythrocytes. PMID- 8498093 TI - Use of single sample clearance estimates of cytochrome P450 substrates to characterize human hepatic CYP status in vivo. AB - 1. Single sample clearance estimates (CL/F) of orally administered ethosuximide were obtained in four groups of healthy adult subjects. One group was treated with phenobarbital to induce CYP2B/2C and CYP3A activity; one group was treated with rifampin to induce CYP3A activity; one group consisted of cigarette smokers (increased CYP1A activity), and one group was untreated (controls). Ethosuximide CL/F values were slightly, though not significantly, increased among cigarette smokers (12.5% increase) and the phenobarbital group (25% increase), but rifampin treatment resulted in a significant increase (65%). 2. The influence of rifampin treatment on the single sample oral clearances of antipyrine, theophylline, phenytoin, carbamazepine, ethosuximide, quinidine, valproic acid, and lorazepam was investigated to determine whether rifampin induces only CYP3A. Rifampin treatment significantly increased the oral clearance of each drug from 1.4-fold (valproic acid) to 3.4-fold (quinidine). These findings indicate that the inductive effect of rifampin extends well beyond CYP3A. PMID- 8498094 TI - Activation of 2,4-diaminotoluene to proximate carcinogens in vitro, and assay of DNA adducts. AB - 1. 2,4-Diaminotoluene, which yields adducts with DNA in vivo, has been studied for its ability to form adducts in vitro. Metabolic activation with rat liver post-mitochondrial supernatant gave 300 adducts/10(6) nucleotides in calf thymus single-stranded DNA, under defined experimental conditions. 2. 2,4-Diaminotoluene modified DNA and deoxyhomopolymers showed characteristic u.v. absorption spectra, exhibiting hyperchromic effects at 235 and 220 nm, and hypochromic effect at 260 nm. The difference spectra between diamine-modified and untreated DNA, or deoxyhomopolymer, were very similar to the spectrum of 2,4-diaminotoluene alone. 3. 2,4-Diaminotoluene-modified DNA was assayed by ELISA with specific monoclonal antibodies directed against diamine-DNA adducts. Reactions with poly-d(A) or poly d(A-T) gave no spectral modification, and immunochemical analysis showed that the diamine did not bind to these polynucleotides. On the other hand, in the case of poly-d(G) or poly-d(C-G), strong immunoreactions were observed, demonstrating that the guanine base is involved in the binding of the diamine to DNA. 4. Monoclonal antibodies directed against different diamine-DNA adducts have shown that 80% of the in vitro metabolic activation involves the para amino group of the aromatic diamine. PMID- 8498095 TI - Effects of phenolic compounds on bromobenzene-mediated hepatotoxicity in mice. AB - 1. The hepatic protective effects of the phenolic compounds 7,8-dihydroxyflavone, morin, silymarin, caffeic acid and chlorogenic acid on bromobenzene-induced toxicity in mice were studied. 2. Morin, caffeic acid and chlorogenic acid at an oral dose of 200 mg/kg failed to influence hepatotoxicity in vivo, while 7,8 dihydroxyflavone exhibited efficacy and potency higher than those of the reference compound silymarin. 3. 7,8-Dihydroxyflavone, an antioxidant and hepatoprotective agent in vitro, decreased serum glutamate-pyruvate transaminase levels (SGPT) in a dose-related manner, and at 200 mg/kg inhibited bromobenzene induced glutathione depletion in liver. PMID- 8498096 TI - [Psychological and physical compromises in patients with organic cerebral psychosyndrome--analysis of treatment success]. AB - The extent of psychic and physical disturbances of patients admitted to the Center of Psychiatry in Frankfurt/M. because of organic psychosyndromes in the year 1988 was analysed. Especially the results of the hospital treatment and the proceeding mode of caretaking were examined. Usually an unspecific state of confusion was the main reason for admittance of most of the patients (n = 59). The majority of the patients suffered from a mid-ranged to marked state of dementia. The results of the treatment for these patients was highly significantly worse compared to patients admitted with a psychosis or a depressive syndrome. A non-significant statistical correlation was found for the results of the medical treatment and medical diseases. Concerning the treatment with psychic drugs a pragmatistic order was used. Analysing the results no advantage of a treatment with up to 4 different drugs compared to a monotherapy could be found. Patients who were not treated with psychic active substances tended to have a poorer outcome. At the end of the stay in the hospital 25.4% of patients were classified with a good outcome after treatment, 49.2% had a slight degree of recovery. PMID- 8498097 TI - [Gerontopsychiatric management in a university clinic]. AB - The patients of the Heidelberg Section of Gerontopsychiatry in 1990 (99 persons aged between 52 and 97 years) were studied in respect to their social data, medical history, severity of illness, and extent of their need of nursing care. Of special interest was how they coped after release from the hospital. In comparison to a study performed in 1982/83, there were many more old and (especially physically) severely impaired patients. We also found an increased percentage of transferrals to nursing homes. The results are discussed with regard to gerontopsychiatric care in the Heidelberg area. PMID- 8498098 TI - [6th Annual Meeting of the Brain Society combined with the Annual Meeting of the Austrian Alzheimer Society 19-21 March 1992 in Salzburg. Summary of the results of the Brain Society sponsored scientific projects]. PMID- 8498099 TI - [Constitutional types of bioelectric activity of the brain and genetic susceptibility for cerebral vascular pathology]. AB - Study of the mathematical model of processes of the brain's bioelectric activity such as Pugachev's canonical decomposition has allowed to establish the association between the degree of quasi-determination of the study processes, and the hereditary disposition in development of cerebral vascular pathology. The results obtained have been used for the development of an effective, automated system of prognostication of the pre-clinic stages of cerebral stroke. PMID- 8498100 TI - [Test battery for objective assessment and differential diagnosis in the early stage of suspected development of presenile dementia of the Alzheimer type]. AB - The clinical diagnosis of organic brain syndromes (especially of primary degenerative dementia) in their early stages is uncertain or only tentative. We used a set of relatively simple tests to support the hypothesis that the disturbance of several operational brain functions precedes memory decline in primary degenerative dementia. Twenty-one patients with early stage, presenile onset of DAT, 14 patients with cardiovascular disease (CVD) and a questionable dementia, an age-matched control group (EC, n = 15), and a younger control group (YC, n = 16) were examined in the following tests: labyrinth learning test, tactile and visual pattern recognition, different reaction time tasks, eye tracking, finger-tapping, alpha-EEG-blockade, photic driving, flicker fusion frequency, and interaction tasks. The test demonstrated that the patients performed more slowly for all tasks than did control subjects. The CVD patients performed better than the DAT group, but they were also significantly worse in the tests compared with healthy elder subjects. This test battery was found purposeful for early diagnosis of both primary degenerative and other forms of dementia, and may also be helpful to exclude other forms of organic brain syndromes. PMID- 8498101 TI - [The Geriatric Concentration Test. Results of a study of patients over 65 years of age in Mannheim]. AB - The validity of the Alters-Konzentrations-Test (AKT; Geriatric Concentration Test) developed by Gatterer (7) was tested in a sample of 33 psychiatric patients and 28 residents of an old people's home 65 years of age and older. The AKT evaluation correlated significantly with the diagnosis of dementia according to the Feighner criteria in the old people's home sample for which a cut-off of 47/48 was used. However, there was no significant correlation in the sample of psychiatric patients. The AKT score correlated with the values from other procedures for evaluating cognitive performance. In the old people's home sample, the AKT scores were significantly associated with self-reported activities of daily living as well as with activity and mood of the probands reported by the head of home; this, however, is not true for the hospital patients. PMID- 8498102 TI - [Epidemiology of medication suicide attempt in the elderly]. AB - We studied 38 geriatric patients admitted to our observation ward after attempted suicide by drug ingestion. Age and sex distribution, social status, time of attempt, drugs and therapeutic procedures were registered and compared to suicide attempts of other age groups (n = 231). Our analysis showed that geriatric attempted suicides differed from those of other age groups by less exogenous influences, in motivation, methods and therapeutic procedures. They may represent an own entity of disease nearer to suicide than to attempted suicide. PMID- 8498103 TI - [Common memory aids of younger and older people]. AB - This study investigates the use of internal and external mnemonics in everyday life. External mnemonics were assumed to be less capacity demanding than internal ones. Additionally, we expected the use of internal techniques to be reduced in western societies because of an environment changing towards a "world of external storing devices". Thirty students and 20 institutionalized old people were interviewed about their everyday use of mnemonics. The interviews were based on Harris' mnemonics questionnaire (1980). Our results indicate students using internal as well as external mnemonics, although for more external ones. In general, the same is true for the institutionalized elderly. However, 1) they mainly use external aids, and 2) in total, they use fewer mnemonics than students. These results contradict the general assumption of old people compensating for memory problems by increasingly relying on mnemonics. Instead, the dominance of external aids indicates a tendency to process information more economically. Overall, the results suggest the necessity of further investigating the conditions for a successful use of external aids in everyday life. PMID- 8498104 TI - [Formation of an integrated milieu on a gerontopsychiatric unit]. PMID- 8498105 TI - [The role of the central nervous system in controlling hibernation]. AB - Bibliographic and original experimental data related to the problem of the role of central nervous system in controlling hibernation are analyzed. It is shown that limbic structures (septal zone, hippocamp, hypothalamus) are of great significance. Taking into consideration the key role of medial septum as a generator of hippocampal theta-rhythm, the elevated excitability of septal neurones in brain slices obtained from hibernating animals and other experimental data, a conclusion is drawn about the role of medial septal nuclear complex as the forebrain "watch point" in hibernation. The significance of thyrotropin releasing hormone in controlling the waking/hibernation cycle is discussed. PMID- 8498106 TI - [Mechanisms of the selective development of neuronal structures]. AB - The review deals with a complex of problems concerned with interneuronal relationship formation in the central nervous system. Hypothesis of neuronal selection, role of trophic factors in formation and maintenance of interneuronal connections, mechanism of their synaptic stabilization are analyzed. It is noted then signals ingoing from afferent inputs in the process of development modulate the activity of neurones and thus interact with the mechanisms of nervous system self-organization. On the basis of current knowledge about causes of the stabilization of neuronal interconnections structure, as well as original investigations, a hypothesis on mechanism of local neuronal systems selection depending on the stability of their impulse outflow is proposed. PMID- 8498107 TI - [Factors that determine the specificity of neural activity in early ontogeny]. AB - Among the main factors determining the specificity of central nervous system functioning in the early ontogenesis, the principal role is assigned to the next ones: 1) Non-maturity of neural elements, their interconnections, regulatory and controlling mechanisms; 2) Heterochronism in structures and functions maturation; 3) Functional recapitulation; 4) The principle of structural and functional excessiveness; 5) Age-related inhibition of the ability of neural structures to periodic self-excitation and long-lasting self-maintaining reactions to afferent stimulation. The role of those factors is illustrated on examples of activity of non-mature nervous systems, proper to early neuro-ontogenesis of chick embryo and non-maturonate mammals, including man. PMID- 8498108 TI - [The patterns in the functioning of the hypothalamo-hypophyseal-adrenal cortex system]. AB - Main principles of functioning of the hypothalamus-hypophysis-adrenal cortex system (HHACS) in conditions of stress activation and rhythmic excitation and inhibition are characterized. Interrelations between input signals, disturbing the HHACS, and output parameters of its activity, are described. The role of central and peripheral parts of HHACS in the realization of the principles of its functioning is analyzed. The concept on the significance of HHACS construction as a system of three hormonal links is considered. The dependence of adaptive capacities of the body on the HHACS state is characterized. Recently discovered features of corticosteroid hormones as agents increasing adaptive resources--the antinociceptive and the antiulcer actions--are discussed. PMID- 8498109 TI - [The amygdala-caudate system and behavior]. AB - Discussion of the cortical-subcortical interactions in organization of the behavioral reaction of various biological significance. Analysis of vast original experimental data on the morphology of the amygdala-caudate relations, on the neuron reconstructions in the cortical-subcortical systems under the positive and inhibitory conditioned reflexes, on the role of individual nuclei of the amygdaloid body in the trophic and defensive reactions, in organization of internal inhibition. PMID- 8498110 TI - [Changes in the phospholipid and cholesterol content of rat tissues during adaptation to high altitude at different environmental temperatures]. AB - Studies have been made on the contents of total lipids, cholesterol, phospholipids and the level of lipid peroxidation in rats adapted to a high altitude (3.200 m for 30 days) at temperatures 10 and 30 degrees C. It was shown that at lower temperature, high altitude adaptation is paralleled by more significant activation of lipid peroxidation, the decrease of phosphatidylcholine and phosphatidylethanolamine in the brain, lungs and liver, as well as by the increase of the content of phosphatidic acid and phosphatidylinositol in tissues. No negative cross-adaptation was found to hypoxic hypoxia and low temperatures. PMID- 8498111 TI - [The effect of vasotocin and mesotocin on the suprarenal gland of the frog Rana temporaria in vivo and in vitro]. AB - Biochemical and morphometric analyses have been made of the effects of nonapeptide neurohormones, vasotocin and mesotocin, on the chromaffin tissue of the adrenal gland of the frog, both in vivo and in vitro experiments. It was shown that vasotocin exerts stimulating effect on the suprarenal gland whereas mesotocin inhibits the latter. In vitro experiments revealed that adrenalin may abolish the effect of nonapeptides on the suprarenal gland. PMID- 8498112 TI - [The correlation of 2 self-regulation circuits of pancreatic secretion in ontogeny]. AB - In 1-2-month puppies, unlike adult dogs, intraduodenal administration of pancreatic enzymes does not result in selective inhibition of pancreatic secretion of the enzymes. Formation of selective inhibition of secretion of enzymes and bicarbonates in ontogenesis is not simultaneous. In early postnatal ontogenesis, feedback regulation of pancreatic secretion from the duodenum appears after feedback regulation of the secretion by means of direct inhibitory effect of pancreatic enzymes of the blood. PMID- 8498113 TI - [The development of sleep phases and thermoregulation in the early ontogeny of rats]. AB - In newborn Wistar rats, studies have been made on the EEG parameters of the cortex and hippocamp, as well as on the dynamics of temperature in the brain and cervical muscles in the awake state, quiet (QS) and active (AS) sleep. With respect to most of the investigated parameters, QS and AS correspond to slow wave and paradoxical sleep of adult animals. Stable EEG patterns in the form of synchronization of bioelectrical activity during slow wave sleep or desynchronization during paradoxical one were found in rat puppies beginning from the 7th day. The increase in the brain temperature together with the decrease in muscle temperature during separate moments of AS, as well as the decrease of both temperatures during QS were observed already in 4-day rat puppies. The data obtained suggest that close correlation between thermoregulation and sleep is formed in mammals already at early stages of postnatal life. PMID- 8498114 TI - [The forms of cognitive activity in monkeys and apes]. AB - Cognitive functions were compared in three species of primates (Cebus apella, Macaca mulatta, Pan troglodytes). Under identical conditions, studies have been made on the ability of identify two-dimensional natural images corresponding to three-dimensional objects basing on a modified "sample-to-sample" method. It was shown that monkeys learned to solve these tasks via multilevel combination of visual pictures with voluminous objects, being able to translate the principle elaborated from one set of stimuli to another. Apes exhibit the ability of direct translation of two-dimensional objects to three-dimensional ones using former experience in solving new tests of various complexity. PMID- 8498115 TI - [The laminar distribution of the neuronal sources of afferent fibers to the neocortex in the caudal regions of the limbic cortex in rats and cats]. AB - Laminar distribution of neurones in the caudal limbic cortex, which form projections to the neocortex, has been studied by axonal transport of HRP. It was shown that the associative parietal cortex (field 7) receives the greatest part of limbic afferents from neurones of layer V. It is suggested that field 7 is included in the limbic efferent system together with subcortical structures of the brain. Projections of the limbic cortex to the field 7 originate partly from associative neurones of layer III which are more numerous in cats than in rats. PMID- 8498116 TI - [The activity and properties of the adenosinetriphosphatases of flatworms]. PMID- 8498117 TI - [An analysis of the trends in the development of evolutionary physiology based on the materials from conferences dedicated to L. A. Orbeli]. PMID- 8498118 TI - [The functional aspects of the evolution of ras proteins]. PMID- 8498119 TI - [Fundamentals of comprehensive prevention of the post-traumatic fat embolism syndrome]. AB - Urgent top standard provisions implemented as soon as possible after serious injuries with the aim to prevent the development of shock or treat incipient and developing shock are among the most important aspects of prophylaxis of the traumatic fat embolism syndrome (FE). These provisions comprise quantitative and qualitative replacement of blood losses, prevention of spasms of the peripheral blood vessels, restoration of the microcirculation, maintenance of the acid-base equilibrium and a normal state of coagulation, normalization of fluctuations of the post-traumatic metabolic and humoral response, blocking of pathological impulses from the site of the fracture incl. settling of the long bones; suppression of hypoxia, in particular also by artificial pulmonary ventilation; a high caloric intake to prevent excessive development of lipolysis. Surgical operations with the exception of urgent ones which form part of urgent intensive care must be postponed to the time when clinical manifestations of traumatic shock have completely subsided. The group of comprehensive prophylactic provisions comprises also pharmacological measures/drugs and substances which influence the pathogenetic basis associated with the genesis and development of the FE syndrome and the more general syndrome of post-traumatic dyslipidaemic coagulopathy resp. PMID- 8498120 TI - [Bone mass and osteoarthrosis]. AB - In the submitted review the authors analyze problems of changes of bone mass and mineralization in patients with osteoarthritis and the relationship to osteoporosis. The authors review also methods of assessment of mineral status. PMID- 8498121 TI - [Experimental and clinical study of the Poldi isoelastic cervico-capital endoprosthesis. II. Clinical study]. AB - In the second part of the paper on isoelastic cervicocapital prostheses the authors describe a group of patients with an implanted endoprosthesis. The selection of indication for implantation was very strict and the group of patients is very homogeneous. The endoprosthesis was implanted to biologically old patients with fractures of the neck of the femur where it was not possible to select treatment other than implantation of a cervicocapital prosthesis. The group of patients was evaluated subjectively according to a questionnaire sent to the first 50 patients, and objectively, i.e. by analysis of the clinical and radiological examination. A total of 85 patients were evaluated after more than two years after the implantation. Clinical examination revealed in almost 60% of the patients pain in the central part of the femur of changing quality. For evaluation of the effect the authors assessed the ability to walk and the quality of gait. Despite the above mentioned complaints 76% of the patients were able to walk unaided. By evaluation of the X-ray findings the authors did not only find evidence of osteoplastic reactions in the region surrounding the bone but also the probable cause of pain suffered by the patients, i.e. inadequate contact of the inner corticalis of the femoral cavity of varying width with the uniform shank. The most serious complication was fracture of the shank of the endoprosthesis, always at a typical site. This occurred in five patients from a total of 130 operated ones, i.e. in 3.8%. Modifications which led to the solution of this problem influenced, however, the elasticity and applicability of this prosthesis. Further investigations made in this group are compared in the discussion in great detail with available data on all other three so-called isoelastic prostheses used in other countries world-wide. In the conclusion the authors evaluate the positive and negative aspects of the endoprosthesis and they emphasize the necessity of certain technical modifications needed for future use of this type of implant. PMID- 8498122 TI - [Closed spongioplasty technique (preliminary report)]. AB - The authors demonstrate in their preliminary report the possibility of careful percutaneous application of spongy bone in the form of a bone paste. For collection of specimens and application of spongy bone the authors use instruments originally designed for transpedicular spongioplasty of fractured vertebrae of the thoracolumbar spine. The described procedure was used in four patients where the risk of complications, local or general, associated with classical spongioplasty was considerable. Healing occurred in all patients within a relatively short time. PMID- 8498123 TI - [Present possibilities and perspectives in rheumato-orthopedics]. AB - After a brief introduction the author expands on specific problems in patients with rheumatoid arthritis and indications of rheumo-orthopaedic operations. He gives an account of the main objectives of these operations, i.e. prevention of deformities and correction of existing deformities, restoration or improvement of mobility and at least palliative influencing of pain. In the subsequent part the author discusses pre- and postoperative care. In the main part of the paper the author deals with his own rheumo-orthopaedic operations with emphasis on preventive and curative operations (synovectomies). As to reconstruction operations, he mentions resections in different anatomical areas, arthrodeses. He emphasizes in particular arthroplasties--from hemiarthroplasties to articular prostheses, so-called total endoprostheses. In the present paper the author analyzes in detail modern concepts, in particular in total endoprostheses of the hip joint, knee and minor joints of the hand. PMID- 8498124 TI - [Initial clinical experience with BAS O, a bioactive glass-ceramic material]. AB - The authors describe a group of patients where the surgical operation involved among others filling of bone defects with glass-ceramic material--dense (as granules) or porous (as a block). Glass-ceramics BAS O were developed in the laboratories of LASAK Co. in Prague. Two defects were of traumatic origin and osteosynthesis was part of three operations. The remaining defects were juvenile bone cysts, fibrous dysplasia and benign bone tumours. The follow-up period after operation varied in the first 11 patients between 6 months and 2 years. In patients of the mentioned group no problems of healing of the surgical wound were recorded nor allergic and side-reactions. The incorporation of glass-ceramic material was followed up by X-ray after three-months intervals. In no instance lighter areas were found on the X-ray pictures suggesting a fibrous outer layer. On the contrary, the trabeculae reached gradually its close vicinity. Based on experience from experimental work and investigation of X-ray signs of healing, the patients were allowed to burden the operated extremity after three months. The basic laboratory examinations made in these patients were within the normal range. In particular calcium throughout the investigation period in the normal range, the phosphorus levels varied near the upper borderline, alkaline phosphatase levels were in many young patients elevated and acid phosphatases varied. In eight patients during the postoperative period eosinophilia was revealed in the haemogram. PMID- 8498125 TI - [Fracture of the axis--surgical treatment. II. Axial isthmus]. AB - The authors present their own experience with the surgical treatment of fractures of the isthmus axis. They discuss contemporary classifications and give indications for surgical treatment. They consider direct compressive osteosynthesis, as described by Judet, performed by a posterior approach as excessively risky for the patient because of possible damage of the vertebral artery and structures of the spinal cord. They substituted this operation by indirect stabilization on Decaulx' principles. The advantage of this method, using an anterior approach, is also immediate treatment of the damaged disc. The authors describe their own experience with both techniques and similarly as in surgical stabilization of the dens they consider it the method of choice. In all cases of surgically treated isthmic, dislocated fractures a firm osseous connection was established with practically no functional restrictions of the cervical segment. PMID- 8498126 TI - [Degenerative changes in the small joints of the hand in adults]. AB - Based on a macroscopic investigation of 137 joints of humans aged 50-90 years, using necroptic material from the Institute of Anatomy, the authors describe the course of the degenerative process and its localization on the contact surfaces of different joints. Concurrently the author describes also changes of the synovial layer of the articular capsule in relation to changes of the articular cartilage. PMID- 8498127 TI - [The preoperative plan in orthopedics (case reports)]. AB - At present due to the development and availability of different types of implants for orthopaedic surgery the orthopaedic surgeon must resort to static and biomechanical thinking. Therefore he does not always appreciate the metabolic function of osseous tissue. This fact is demonstrated on three case-histories. In the first case, after well performed Kuntscher osteosynthesis of a femoral fracture, the surgeon did not take a sample for histological examination. A subsequent complicated clinical course and histological examination revealed a pathological fracture associated with an osteosarcoma. Another case-history describes the difficulties associated with creating sufficient space for inserting the shaft of the femoral component for Looser's zone. In case-history no. 3 after rapid weight loss because of overweight the patient developed osteoporosis. The authors reflect whether it is justified to indicate strictly weight reduction before implantation of a total endoprosthesis without evaluation of metabolic aspects of weight loss. When the metabolic function of osseous tissue will be taken into account, the authors assume that the late postoperative results will be better. PMID- 8498128 TI - Total quality management in cytology. AB - The total quality management (TQM) process was incorporated into the operation of the Cytology Department, Wisconsin State Laboratory of Hygiene, in January 1991. TQM was successful in identifying inefficiencies in laboratory practices and in developing mechanisms for improvement in laboratory operation. Within four months the turnaround time was reduced from 71 to 15 days. Participatory management also resulted in marked improvements in all facets of departmental operation. Since the Clinical Laboratory Improvement Act of 1988 mandates a system to respond to problems arising between the laboratory and individuals who order tests, many cytology laboratories will undoubtedly turn to TQM to manage their operations in a customer-oriented fashion. For hospital-based laboratories, Joint Commission on Accreditation of Healthcare Organizations rules will also require a customer focus. Cytologists desiring to embark on TQM can learn more about the system from books, journal articles and seminars. PMID- 8498129 TI - Immunocytochemical detection of ovarian carcinoma cells in serous effusions. AB - Monoclonal antibodies OC 125, OV632, OV-TL 3, MOv18 and OV-TL 23, directed against distinct ovarian carcinoma-associated antigens, were examined for their value in cytopathologic diagnosis. Their sensitivity and specificity in staining ovarian carcinoma cells in serous effusions we determined using the indirect immunoperoxidase technique. Smears prepared from 140 serous effusions (73 benign, 67 malignant) were immunostained with the five antibodies. OC 125 and MOv18 reacted positively with 96% and 81% of the smears of effusions from ovarian carcinoma patients, respectively, while OV-TL 3, OV632 and OV-TL 23 stained a lower percentage of the samples (73%, 65% and 62%, respectively). In discriminating ovarian carcinoma cells from benign (mesothelial or inflammatory) cells in serous effusions, MOv18 demonstrated the highest specificity (100%) since none of the 73 samples from benign effusions were stained upon incubation with this antibody. OC 125 cannot be used for this purpose due to its reactivity with mesothelial cells in benign samples. Staining cytologic preparations of malignant effusions from cancer patients with carcinomas not originating in the ovary revealed that OV632 and OV-TL 23 may be useful adjuncts to determine the origin of the carcinoma cells found in serous effusions. The reactivity of these antibodies was highly selective for ovarian carcinoma cells, staining only 6% and 0% of the samples from the non-ovarian carcinoma samples, respectively. It is concluded that MOv18 is the most suitable antibody for distinguishing ovarian carcinoma cells from mesothelial cells in serous effusions, while OV632 and OV-TL 23 especially may help to assess whether carcinoma cells found in effusions originate in the ovary. PMID- 8498130 TI - Intraoperative cytology as an elective surgical procedure. Analysis of 57 cases. AB - Fifty-seven consecutive cases submitted by surgeons for intraoperative cytology were reviewed. In 47 cases there was a concomitant biopsy from the same anatomic site; among them, the cytologic and surgical diagnoses agreed in 44 (94%). The three discordant cases (6%) represented false-negative frozen sections. In the remaining 10 cases the cytologic and surgical biopsy sites differed in 5, 4 were considered inadequate for cytologic interpretation, and 1 did not have a corresponding surgical biopsy. Attitudes toward the use of intraoperative cytology were assessed with questionnaires sent to surgeons from all specialties represented at the University of California, Davis, Medical Center. Fifty-three percent of the respondents reported use of this procedure. At our institution thoracic surgeons and otorhinolaryngologists were more apt than others to use intraoperative cytology as an adjunct to frozen section analysis. Factors influencing their selection of intraoperative cytology are discussed. PMID- 8498131 TI - Cytologic and histologic changes in irradiated loops of transplanted small bowel. AB - The histopathologic and cytopathologic changes in irradiated transplanted loops of bowel were assessed in 10 dogs. Five received conventional radiotherapy (CRT), and five received hyperfractionated doses of radiotherapy (HFRT) over the same period. Both groups exhibited identical cytologic findings, including blunting of villi and significant crypt atypia that could be mistaken for malignancy. Histologic examination corroborated the cytologic findings. At the end of the experiment two of the dogs that received CRT had developed strictures. One showed extensive submucosal fibrosis, while the other showed submucosal atrophy. PMID- 8498132 TI - Aspiration biopsy cytology of smooth muscle tumors. A cytologic approach to the differentiation between leiomyosarcoma and leiomyoma. AB - From 1970 to 1991, 51 cases of smooth muscle tumors were diagnosed by fine needle aspiration biopsy. All were verified histologically and/or clinically, with no false-positive results. Of the 51 tumors, 41 were leiomyosarcoma and 10 leiomyoma. Among the 41 cases of leiomyosarcoma, 29 were the well-differentiated type; 8, poorly differentiated type; and 4, epithelioid type. Of the 10 cases of leiomyoma, 2 were the epithelioid type. The cytomorphologic features and cytologic patterns of various types of smooth muscle tumors observed in aspirate preparations are presented and compared in order to establish the cytologic criteria for differentiating malignant from benign smooth muscle tumors. Cytomorphologically the various types of smooth muscle tumors were different, and their cytologic features were sufficiently distinctive to distinguish one from the others. It appears possible to differentiate a well-differentiated leiomyosarcoma from a leiomyoma on the basis of cytologic findings observed in aspirate preparations. The recognition of different cytomorphologic features of various types of smooth muscle tumors is important in establishing an accurate cytologic diagnosis, which may be of practical significance to clinical management. PMID- 8498133 TI - Morphologic diagnosis of Hurthle cell tumors of the thyroid gland. AB - Despite difficulties in differential diagnosis, aspiration cytology offers unique advantages in the preoperative diagnosis of Hurthle cell (HC) tumors of the thyroid gland over immunocytochemistry and micromorphometry, which have not achieved the anticipated success in the diagnosis of HC tumors. Aspiration cytology is comparable, in terms of speed and accuracy, to microspectrometry of DNA content in HC tumors, a technique that is not convenient for routine use. Detailed morphologic analysis of 19 characteristics of the smears and of the cells revealed five parameters adding to the sensitivity, specificity and reliability of routine diagnosis: HC collection in the form of nests, marked or at least moderate anisocytosis and anisokaryosis, multinucleation and emphasized nucleoli. All five criteria are found in > 70% of HC tumors, and the rate of false positives is < 50%. The simultaneous presence of three or four of these five parameters occurred in 70-90% of HC tumors and would lead to a false positive diagnosis of HC tumors in only 30% of cases. Routine cytologic diagnosis of HC tumors of the thyroid gland may be improved by adoption of these criteria. PMID- 8498134 TI - Fine needle aspiration biopsy of fibromatoses. AB - Fibromatoses form a spectrum of clinicopathologic entities characterized by the infiltrative proliferation of fibroblasts that lack malignant cytologic features. Fibromatoses present as nodular soft tissue masses almost anywhere in the body and thus are often amenable to fine needle aspiration (FNA). This report describes the FNA cytologic findings of fibromatosis in six patients ranging in age from 7 1/2 weeks to 36 years. Two of the lesions arose in the abdominal wall (musculoaponeurotic fibromatosis or extra-abdominal desmoid), and one each involved the plantar surface (Ledderhose's disease), the shoulder and the sternocleidomastoid muscle (Fibromatosis coli). The FNA of the shoulder was initially interpreted as nodular fasciitis due to the clinical presentation of a rapidly growing mass; an aspirate from the deep musculoaponeurotic region was believed to reveal a low grade sarcoma. The FNA diagnosis of musculoaponeurotic fibromatosis in a patient with familial polyposis coli suggested the diagnosis of Gardner's syndrome. Cytologically the aspirates consisted of groups of loosely cohesive, bland-appearing, spindle-shaped cells having oval to elongated nuclei and cytoplasmic tags. Individual spindle cells and rare inflammatory cells were also present. The aspirate of fibromatosis coli also contained degenerating skeletal muscle cells. Tissue confirmation was obtained in four cases. We believe that FNA is a useful procedure for the initial and recurrent diagnosis of fibromatoses and in the separation of fibromatoses from other benign and malignant soft tissue lesions. A discussion of other entities that enter into the cytologic differential diagnosis, such as mesenchymal repair, fasciitis and spindle cell types of sarcoma, is presented. From our experience we believe that the clinicopathologic features can suggest the diagnosis of fibromatosis, but histologic confirmation is recommended. PMID- 8498135 TI - Cytodiagnosis of tuberculous lymphadenitis. A correlative study with microbiologic examination. AB - One hundred two of 272 cases of cytodiagnosis of tuberculous lymphadenitis were subjected to mycobacterial examination by Ziehl-Neelsen staining on direct and concentration smears and by culture. Cytomorphologically the cases were categorized into four types: 1, predominantly necrotic material; 2, typical caseating epithelioid cell granulomas and giant cell formation; 3, only noncaseating epithelioid cell granulomas with or without giant cells; and 4, doubtful presence of epithelioid cells. Ziehl-Neelsen staining for acid-fast bacilli (AFB) was positive in 25% in direct smears, 26.5% in concentration smears and 29.5% in both combined. The cultures for mycobacteria were positive in 49%; combined smear and culture positivity was found in 56.9%. Maximum culture positivity was seen in cases with type 1 smears (56.9%) followed by types 2 (44%) and 3 (40%). The percentage of AFB positivity was similar in type 1 and type 2 smears (32.2% and 30%, respectively); however, AFB were present in large numbers in type 1 smears as compared to type 2 and 3 smears. In type 3 smears AFB positivity was found in 20% of cases. Cases with type 4 smears were negative for AFB in smears and culture. In eight cases (7.8%) the smears were positive for AFB, whereas the cultures were negative, indicating that negative culture examination still does not exclude the possibility of tuberculosis. However, culture is essential to a characterization and determination of drug sensitivity. PMID- 8498136 TI - Fine needle aspiration cytology of the breast with immediate reporting of the results. AB - The value of fine needle aspiration cytology (FNAC) of the breast with immediate reporting was determined in 503 consecutive aspirates. When the results of immediate and routine cytologic examination were compared, there was perfect agreement in 95.8% of the cases, with a kappa score of .92. In only 21 cases did discrepancies occur (4.2%), and when the results of FNAC were divided into normal and abnormal cytology, only four discrepancies were apparent. Provided that the results of immediately reported FNAC are interpreted in the context of clinical and mammographic findings, this approach provides a reliable diagnosis within a quarter of an hour and is therefore highly recommended. PMID- 8498137 TI - Role of nuclear grading of breast carcinomas in fine needle aspiration specimens. AB - Nuclear grade is one of several key prognostic factors that should be addressed in the pathologic analysis of breast carcinomas. A recent National Institutes of Health consensus conference on breast carcinoma recommended that the nuclear grade assignment should be mentioned in pathology reports on such specimens. This retrospective study assigned a nuclear grade to all positive breast aspirates that had tissue follow-up over the previous 23 months. Independent, blind grading of the tissue specimens and aspirates revealed concurrence of nuclear grade assignment in 95% of the cases. Using the same criteria for grading tissue and cytologic specimens, it was concluded that assigning a nuclear grade in breast carcinoma aspirates is done with little effort, is reproducible and, with rare exceptions, depending on sample limitations, correlates precisely with the tissue nuclear grade. Since the nuclear grade provides such important prognostic information and is a fundamental cytologic parameter, the nuclear grade should appear in fine needle aspiration biopsy reports on breast carcinomas. PMID- 8498138 TI - Fine needle aspiration biopsy of renal cell carcinoma. Cytologic parameters and their concordance with histology and flow cytometric data. AB - Fine needle aspiration biopsy (FNAB) is increasingly utilized in the initial diagnosis of renal neoplasms. Nuclear grading assessment, however, has not been applied routinely to these neoplasms, and data on its validity are lacking. To determine the reproducibility and clinicopathologic significance of Fuhrman's nuclear grading (FNG) on FNAB specimens, we retrospectively analyzed cytologic and histologic tissues from 49 cases of renal cell carcinomas (RCC). Our data indicate a high concordance between nuclear grading in FNA material and histologic specimens (80-92%). Moreover, interobserver and intraobserver reproducibility was high (89-92% and 86-96%, respectively). The flow cytometric DNA content of 13 specimens (65%) yielded DNA diploidy in five cases (38%) and DNA aneuploid in eight cases (62%). All eight DNA aneuploid neoplasms were FNG 3 (7 cases) and 4 (1 case), while two of the four DNA diploid neoplasms manifested FNG 3. We conclude that cytologic nuclear grading of RCC correlates with corresponding grading of histologic specimens and could be performed reproducibility for clinical use. PMID- 8498139 TI - Characteristics of cancer cells in gastrointestinal lavage specimens. AB - Cancer cells from the effluent stools resulting from oral gastrointestinal lavage were analyzed. Cellular preparation were done by cytocentrifugation. The method produced cellular preparations that contained from none to 205 cells per slide; the average number was 28. Single cells predominated over groups. The average number of single cells was 13, while three groups were identified on the average slide. The cells were small and averaged 13 microns in diameter and 149 microns 2 in area. The nuclei averaged 8 microns in diameter and 61 microns 2 in area. The nuclear chromatin pattern varied from dense to clumped to vesicular, with the clumped pattern predominating. The technique is simple and easily adaptable and holds promise as a screening technique for gastrointestinal cancer. PMID- 8498140 TI - Cytology of benign cystic uterine adnexal masses. AB - The findings from a cytologic examination of 26 surgically removed cystic adnexal masses (1-11.5 cm) aspirated with a 22-gauge needle were correlated with the histopathologic findings. The mean age of the patients was 48 years. Examination of the Papanicolaou-stained cytospin preparations showed that all but three were cellular. Benign epithelial cells were identified in fluid aspirated from the mass from one patient with hydrosalpinx and from three with paramesonephric and one with simple cysts; they were also found in aspirated samples from three patients with serous cystadenoma and one with serous cystadenofibroma. Masses from the five patients with follicle cysts and cystic follicles contained numerous granulosa cells. Ciliated cells or ciliated cytoplasmic fragments were found in all aspirated samples except those from patients with follicle cysts, cystic follicles or endometriosis. In two patients, one with endometriosis and one with serious cystadenoma, the epithelial cells were atypical, with a high nuclear/cytoplasmic ratio, hyperchromasia, nuclear molding and large nucleoli. These results could be misinterpreted as indicating malignancy. In summary, the vast majority of aspirated samples (91%) contained benign cells. However, caution should be exercised in the interpretation of possibly misleading cytologic findings in patients with endometriosis or cystadenoma. PMID- 8498141 TI - Microfilariae in bronchial brushing cytology of symptomatic pulmonary lesions. A report of two cases. AB - Two cases of pulmonary filariasis with atypical clinical and radiologic features without significant eosinophilia are presented. A diagnosis of pulmonary filariasis could not have been made without bronchial brush cytology, which showed sheathed microfilariae of Wuchereria bancrofti. Both cases responded well to antifilarial treatment, indicating that the microfilariae were not an incidental finding but were responsible for the symptoms and radiologic lesions. PMID- 8498142 TI - Megakaryocytes in bronchial brush cytology. A case report. AB - Megakaryocytes were detected in a transbronchial brush cytology specimen. Their detection led to a diagnosis of essential thrombocythemia. PMID- 8498143 TI - Cytologic diagnosis of metastatic malignant melanoma of the lung in sputum and bronchial washings. A case report. AB - A 60-year-old woman with a fever, productive cough, anorexia, weight loss and past history of malignant melanoma of the finger proved to have metastatic melanoma in both lungs on cytologic study of sputum and bronchial washings. The literature in English over 40 years (1952-1992) gives only a few hints about the value of cytologic diagnosis of metastatic malignant melanoma of the lung. Cytologic features include a variable amount of melanin pigment, isolated or loosely cohesive groups of round to oval cells with eccentric nuclei, regular nuclear outline, anisocytosis, binucleation and multinucleation, fine chromatin pattern and prominent nucleoli. PMID- 8498144 TI - Aspiration cytology of an enlarged thymus presenting as a mediastinal mass. A case report. AB - Fine needle aspiration (FNA) cytology was used to evaluate an anterior mediastinal mass in a 12-year-old girl. The smears showed two cellular populations composed of epithelial cells and many lymphocytes, simulating FNA cytologic features of a thymoma. However, histopathologically the mass proved to be an enlarged and microscopically normal thymus. The different shapes and sizes of the epithelial cell nuclei and lymphocytes encircling the individual epithelial cells present in the FNA smears of the enlarged thymus were features that are not seen frequently in FNA smears of thymomas and therefore may be differentiating points. However, studies of FNA smears from more cases of thymoma and thymic hyperplasia are necessary in order to define FNA cytologic criteria to differentiate these two entities. PMID- 8498145 TI - Quality control in cytologic screening. PMID- 8498146 TI - Fine needle aspiration identification of the adult worm of Brugia malayi and its ovarian fragment from an epitrochlear lymph node. PMID- 8498147 TI - Life events in the pathogenesis of Graves' disease. A controlled study. AB - Contradictory findings have been reported about a possible causal relationship of life stress to Graves' disease. We evaluated this issue by investigating the occurrence of stressful life events in the year before the first signs of disease onset, using methods that have been found to be valid and reliable in psychosomatic research. Seventy consecutive patients with Graves' disease and a control group of 70 healthy subjects, matched for sociodemographic variables, were studied. Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients, not during the acute phase of illness but while on remission, by antithyroid drug treatment. Patients with Graves' disease reported significantly more life events compared to controls (p < 0.001). They also had more independent events (p < 0.001) and events that had an objective negative impact (p < 0.001) according to an independent rater, unaware whether the events had occurred in patients or controls. All categories of events were found to be significantly more frequent in patients suffering from Graves' disease than in controls. By rigorous methods (inclusion of patients with Graves' disease only, careful dating of the onset of symptoms, accurate event definition, delay of the interview upon disease remission, use of a blind rater for judging independence and objective negative impact), our results support the concept of an excess of life events in Graves' disease. Stressful life events may affect the regulatory mechanisms of immune function in a number of ways. Within the extreme complexity of the phenomena implicated in the pathogenesis of autoimmune thyroid hyperfunction, our findings emphasize the role of emotional stress. PMID- 8498148 TI - The effects of propranolol and verapamil on hyperthyroid heart symptoms and function, assessed by systolic time intervals. AB - The effects of acute and chronic administration of propranolol and verapamil on heart rate and systolic time intervals were studied in 10 hyperthyroid patients and 10 normal subjects, both groups without signs of cardiovascular or pulmonary disease. In normal subjects iv propranolol reduced heart rate significantly, and both drugs increased the total electromechanical systole significantly without difference between the drugs. This effect was insignificant when the drugs were given orally. In hyperthyroid patients both drugs reduced heart rate significantly in acute and chronic administration, and no difference between the two drugs was found. Neither drug altered cardiac contractility as assessed by systolic time intervals. These results indicate that the metabolic effects of thyroid hormone on contractility were unaltered and unblocked by the drugs. None of the participants developed signs of heart failure. Verapamil can thus be used as an alternative to propranolol in the treatment of tachycardia in hyperthyroidism. PMID- 8498149 TI - Different responses in little and bigbig prolactin to metoclopramide in subjects with hyperprolactinemia due to 150-170 kD (bigbig) prolactin. AB - We have studied in vivo induction of serum prolactin (PRL) levels in four females and one male, and regulation of PRL in the menstrual cycle in three females all with hyperprolactinemia with large amounts (72-92%) of bigbig PRL (MW 150-170 kD). Metoclopramide (MTC) iv induced a 4-29-fold increase in little PRL (25 kD PRL) at 30 min, while the increase in 150-170 kD PRL was 1.1-2.2-fold. The maximal response in 150-170 kD PRL was seen after 2-6 h, and the decrease after the maximal PRL values for 150-170 kD PRL was delayed compared to the decrease in 25 kD PRL. The different kinetics for 25 kD PRL and 150-170 kD PRL was responsible for the prolonged increase in total PRL seen in the subjects with large amounts of 150-170 kD PRL compared to the controls. The percentage of 150 170 kD PRL decreased to 29-60% at 30 min and returned to unstimulated values after 6-24 h. In contrast, prolonged stimulation of PRL secretion, as in the luteal phase, did not change the percentage of 150-170 kD PRL. In a male subject secreting large amounts of 150-170 kD PRL the increase in PRL after MTC was less, while the temporal changes in the 25 kD PRL levels were almost the same as in the females. PMID- 8498150 TI - Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes. AB - The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre (p < 0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 SD (p < 0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p < 0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1-4 h after ingesting nalmefene and again 12-18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes. PMID- 8498151 TI - Opposite effects of growth hormone and estrogens on the pregnancy zone protein serum levels in children and adolescents. AB - Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 micrograms/l vs 434 micrograms/l; p < or = 0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng.kg-1.d 1 ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone. PMID- 8498152 TI - Plasma corticotropin-releasing hormone, beta-endorphin and cortisol inter relationships during human pregnancy. AB - To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), beta-endorphin (beta EP), cortisol and obstetric events during pregnancy, blood samples were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, beta EP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and beta EP were correlated (r = 0.30, p < 0.001). (3) During labour, no correlations were found among maternal plasma CRH, beta EP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p < 0.05) as were maternal and fetal beta EP (r = 0.43, p < 0.001). (7) Fetal obstetric difficulty was correlated with fetal beta EP (r = 0.54, p < 0.001). Our findings support the hypothesis that maternal plasma CRH regulates maternal beta EP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress. PMID- 8498153 TI - The pattern of gonadotropin and estradiol secretion in exaggerated thelarche. AB - PURPOSE: To assess the dynamics of the pituitary-ovarian axis in exaggerated thelarche, defined as premature thelarche associated with signs of systemic estrogen effects (advanced bone age and/or growth acceleration) without progression to complete puberty. SUBJECTS AND METHODS: Seven girls (age < 2.5 years) with exaggerated thelarche, 6 girls with inactive pituitary-ovarian axis (premature adrenarche) and 21 girls with activated axis (central precocious puberty) had serum FSH, LH and E2 measured serially before and 1 to 24 h after gonadotropin-releasing hormone agonist (GnRHa) administration (leuprolide, 20 micrograms/kg sc), used as a test of combined pituitary-ovarian stimulation. RESULTS: Although girls in the exaggerated thelarche and adrenarche group had similar [mean (SEM)] baseline FSH [3.2 (0.9) vs 1.4 (0.3) IU/l], LH [0.36 (0.1) vs 0.27 (0.02) IU/l] and E2 [20 (1.2) vs 21 (2) pmol/l] concentrations, and similar peak post-GnRHa LH concentrations [5.5 (1.1) vs 2.4 (0.5) IU/l], girls with exaggerated thelarche achieved higher peak FSH [41 (9) vs 14 (3) IU/l, p < 0.01] and E2 [243 (40) vs 37 (6) pmol/l, p < 0.001] concentrations after GnRHa. In comparison to patients with exaggerated thelarche, girls with precocious puberty had higher (p < 0.01-0.001) baseline LH [3.6 (0.8) IU/l], baseline E2 [69(11) pmol/l], GnRHa-stimulated peak LH [68 (17) IU/l] and peak E2 [648 (58) pmol/l] concentrations, but similar FSH parameters. CONCLUSIONS: Girls with exaggerated thelarche exhibit substantial E2 secretory potential that can be demonstrated by GnRHa stimulation, is predominantly FSH-driven, and probably accounts for the manifestations of estrogen effect seen in these girls. PMID- 8498154 TI - Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect. AB - We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 micrograms per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions. PMID- 8498155 TI - Single nucleotide substitution of the androgen receptor gene in a case with receptor-positive androgen insensitivity syndrome (complete form). AB - Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H]dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotestosterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine-->cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine- >alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome. PMID- 8498156 TI - Individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8. AB - The individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity were examined in dexamethasone-treated rat osteoblastic osteosarcoma cells ROS 17/2.8. Dexamethasone-induced alkaline phosphatase activity was inhibited not only by hPTH(1-84) and amino-terminal PTH fragment hPTH(1-34), but also by carboxyl-terminal PTH fragment hPTH(69-84) in a dose-related fashion. At 10(-7) mol/l, hPTH(1-84) completely abolished dexamethasone-induced alkaline phosphatase activity, while hPTH(1-34) and hPTH(69-84) reduced alkaline phosphatase activity to 0.16 +/- 0.02 and 0.80 +/- 0.03 fold, respectively, of the control value obtained in the absence of PTH peptides. The combination of hPTH(1-34) and hPTH(69-84) resulted in reduction of alkaline phosphatase activity to the level obtained by hPTH(1-84). The shorter carboxyl-terminal PTH fragment hPTH(71-84) did not affect alkaline phosphatase activity or modulate the action of hPTH(1 34). The longer carboxyl-terminal PTH fragment hPTH(53-84) stimulated alkaline phosphatase activity up to 1.23 +/- 0.03 fold and partially blunted the inhibitory effect of hPTH(1-34) on alkaline phosphatase activity. These findings suggest that carboxyl-terminal PTH fragments could exert diverse effects on the target cells, depending on the length of deletion of amino-terminal amino acids of PTH molecule, and interact with amino-terminal PTH fragment. The two amino terminal amino acids of hPTH(69-84) and the 53-68 portion of hPTH(53-84) might be responsible for the respective inhibitory and stimulatory effects of the peptides on alkaline phosphatase activity. PMID- 8498157 TI - Effects of free radical scavengers on cytokine actions on islet cells. AB - We investigated the effect of free radical scavengers on the actions of cytokines on islet cells. Interferon-gamma and tumor necrosis factor-alpha reduced the nicotinamide adenine dinucleotide content of mouse islet cells; the combination of interferon-gamma (4 x 10(5) U/l) and tumor necrosis factor-alpha (4 x 10(5) U/l) caused nicotinamide adenine dinucleotide reduction by approximately 40%. Dimethyl urea and dimethyl sulfoxide prevented the decrease, whereas superoxide dismutase, catalase, and mannitol were not effective. Dimethyl urea and dimethyl sulfoxide protected islet cells from the synergistic cytotoxic action of interferon-gamma and tumor necrosis factor-alpha. Major histocompatibility complex class II antigen induction by interferon-gamma and tumor necrosis factor alpha was also inhibited by dimethyl urea and dimethyl sulfoxide, but not by superoxide dismutase, catalase and mannitol. Since superoxide dismutase of a membrane-penetrable form attenuated the class II antigen induction, the inefficiency of superoxide dismutase, catalase and mannitol may be attributable to their inability to penetrate islet cells. These results suggest that the intracellular generation of free oxygen radicals is involved in islet cell cytotoxicity and class II molecule expression by interferon-gamma and tumor necrosis factor-alpha, and that nicotinamide adenine dinucleotide reduction may be associated with islet cell dysfunction caused by the cytokines. PMID- 8498159 TI - Scandinavian Society for the Study of Diabetes. 28th annual meeting. Stockholm, Sweden, 14-16 May 1993. PMID- 8498158 TI - The facilitatory effect of N-methyl-D-aspartate on sexual receptivity in female rats through GnRH release. AB - The purpose of this study was to examine whether N-methyl-D-aspartate affects the sexual receptivity of female rats. Monosodium L-glutamate was used as a neurotoxin to induce hypogonadal status. Matured normal and monosodium L glutamate-treated rats were ovariectomized and implanted subcutaneously with estradiol capsules. One week later, lordosis responsiveness was observed before and 10 min after N-methyl-D-aspartate (40 mg/kg of BW, ip) administration. The results showed that N-methyl-D-aspartate caused a remarkable increase of lordosis quotient in control rats but not in monosodium L-glutamate-treated rats. Moreover, the possible action site of N-methyl-D-aspartate in the enhancement of receptivity was evaluated by the post-castrational LH rise, pituitary LH release in response to GnRH, and N-methyl-D-aspartate-evoked GnRH releasability. The results revealed that: (a) serum levels of LH in monosodium L-glutamate-treated rats were lower (p < 0.01) than those of control rats after ovariectomy; (b) there was no significant difference of pituitary LH release responsiveness to GnRH test between two groups; and (c) N-methyl-D-aspartate-evoked LH release in monosodium L-glutamate-treated rats was similar to that in the control rats. In conclusion, N-methyl-D-aspartate may facilitate the sexual receptivity through stimulating GnRH release. The failure of N-methyl-D-aspartate in enhancing receptivity in monosodium L-glutamate-treated rats is probably due to the cellular damage by monosodium L-glutamate on specific areas responsible for lordosis. PMID- 8498160 TI - Xylitol and the bactericidal effect of chlorhexidine and fluoride on Streptococcus mutans and Streptococcus sanguis. AB - The present study was made to investigate the effect of xylitol on the bactericidal and bacteriostatic action of chlorohexidine diacetate (CHX) and sodium fluoride (F) in ATCC strains of Streptococcus mutans and S. sanguis. Standardized bacterial cell suspensions were used in tests for bactericidal effect and for inhibition of growth and sucrose fermentation. The results showed no interference of xylitol with the antibacterial effect of CHX and F combinations. Xylitol did not show any additive effect either but appeared inert in the combinations used. PMID- 8498161 TI - Symptoms and lesions associated with retained or partially erupted third molars. Some variables of third-molar surgery in Norwegian general practice. AB - A questionnaire on third-molar problems was mailed to a systematic random sample of 200 Norwegian general dental practitioners in November 1991. A 88% return rate was obtained. The following conclusions were drawn: on an average, 3.8 patients with lesions or complaints from retained or partially erupted third molars were seen in general practice in 1 month, and most of these consultations were associated with partially erupted third molars. A mean of 1.3 surgical removals of third molars was performed in general practice in 1 month. The mean one-way travel time for patients to specialists in oral surgery was 1.3 h, and variations were not related to surgical activity in practice. Fourteen per cent of the general practitioners refer surgical cases to non-specialists. PMID- 8498162 TI - A comparison of Flow and Kodak dental X-ray films by means of perceptibility curves. AB - Flow D- and E-speed group dental X-ray films (DX-58 and EX-58) have recently been introduced to the market. By means of perceptibility curves these films were compared with commonly used dental X-ray films (Kodak Ultraspeed and Ektaspeed). No major differences between the films were found with regard to contrast and the subjectively assessed number of small contrast differences. The exposure for EX 58 had to be lowered by 66% and Ektaspeed by 39% compared with Ultraspeed film to obtain the same density. DX-58 and Ultraspeed were of the same sensitivity. PMID- 8498163 TI - Effect of food consistency on the shape of the articular eminence and the mandible. An experimental study on the rabbit. AB - The aim of this investigation was to ascertain what changes masticatory function could elicit in the shape of the articulating surface and the growth of the mandible in a growing rabbit. Forty-seven rabbits were divided into two groups, a control group fed whole pellets and a 'soft' group fed softened pellets and having their incisors shortened once a week. All the rabbits were killed at the age of 50 days and roentgenographed, after which the heads were freed of soft tissues, and the shape of the articulating eminence, the dimensions of the mandible and the maxilla, and intermaxillary relations were measured. The articulating surface of the glenoid fossa was steeper in the soft group, the lower border of the articulating eminence was located more inferiorly, and the mandible was more retrognathic. It is concluded that the difference in functional stress affects the shape of the articular eminence and the intermaxillary relationship. When the condyle is functioning more on the eminence, the latter becomes flatter, and the mandible moves forwards. PMID- 8498164 TI - Cusp fracture of endodontically treated posterior teeth restored with amalgam. Teeth restored in Denmark before 1975 versus after 1979. AB - The aim of the present study was to analyze the frequency and the severity of cuspal fracture for posterior teeth endodontically treated by 91 Danish dentists and restored with amalgam either before 1975 or after 1979. A database from a previous study was analyzed (1584 teeth with an MO, a DO, or an MOD amalgam restoration without cuspal overlays). Teeth restored before 1975 had a significantly lower frequency of cusp fracture than teeth restored after 1979. Moreover, when comparing the frequency of subcrestal fractures, that of the second group (after 1979) was more than twice as high as that of the first group (before 1975). Two factors with a bearing on these findings changed in the time period 1975-1979; the high-copper amalgams took over in Denmark, and the use of Gates-Glidden burs to achieve straight-line access to the root canal was introduced. It is suggested that the weakening of the coronal part of the root, caused by the use of Gates-Glidden burs, and the expansion and low creep of high copper amalgams may be two of the reasons for the increased frequency and severity of cuspal fracture found in the past decade in Denmark. PMID- 8498165 TI - The absence of correlations between a clinical classification and ultrastructural findings in amelogenesis imperfecta. AB - This study was performed to examine whether a clinical classification of different phenotypes of amelogenesis imperfecta could be discernible at the ultrastructural level. Seventeen primary teeth from 16 children with hypomineralization, hypomaturation, or hypoplastic variants of the disease were collected for histologic studies of the enamel by means of polarized light microscopy, scanning electron microscopy (SEM), and secondary ion mass spectrometry (SIMS). Polarization microscopy showed that the enamel was hypomineralized; in six teeth a wavy configuration of the enamel prisms also appeared. Three histomorphologic main types could be discerned. In 10 of the teeth extensive hypomineralization of the bulk of the enamel was found. One tooth had an unusually thick enamel with only a thin normally mineralized surface layer. SIMS images showed less pronounced signals from Ca2+ and Na+ but with stronger signals from Cl- and CN-, representing the organic component of enamel. The SEM images showed an irregular prism pattern with marked interprismatic areas. Irrespective of the clinical appearance or the hereditary pattern the main findings were hypomineralized enamel with or without wavy bands. Neither of the analytical methods used in this paper distinguishes between the clinical phenotypes of amelogenesis imperfecta. PMID- 8498166 TI - Clinical evaluation of glass ceramic inlays (Dicor). AB - The purpose of the study was to evaluate the clinical behavior of ceramic class II inlays (Dicor) in the first 2 years after placement. As a reference, a similar number of dental amalgam restorations were followed up during the same period. Twenty-five inlays and 25 dental amalgams were placed on premolars and first molars of 20 and 19 patients (15-19 years old), respectively. The inlay preparations were made in accordance with the manufacturer's recommendations, and the inlays were produced by a licensed Dicor laboratory. The inlays were luted, using a glass ionomer cement. The dental amalgam preparations were made using standard class-II preparation techniques and filled with ANA 2000. The inlays were evaluated after 6, 12, and 24 months, and the dental amalgam restorations after 24 months, using the criteria suggested by Ryge. In addition, the 24-month examination included proximal recording of dental plaque and gingivitis. With the exception of two inlays that fractured during the observation period, all ceramic inlays showed excellent ratings for anatomic form, marginal discoloration, and marginal caries at all examinations. Two inlays showed minor marginal defects but were classified within the range of acceptance with no need for replacement. The two fractured inlays were replacements of earlier fractured dental amalgams. The clinical behavior of the dental amalgam restorations was in most respects similar to that of the ceramic inlays. Unlike the inlays, however, no dental amalgams fractured during the observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498167 TI - Wear resistance of some prosthodontic materials in vivo. AB - The purpose of this study was to compare a gravimetric method and an impression technique in the evaluation of occlusal substance loss. The wear of gold, porcelain, and microfilled resin was studied in vivo. The gravimetric method showed lower substance loss for porcelain than for gold, whereas the microfilled resin had the highest substance loss. To obtain a higher accuracy for the measurement of occlusal substance loss of restorative materials with an impression technique, the test area has to be restricted, the antagonizing occlusal contacts carefully recorded before the test period, and the number of cuts increased. The observed structure of wear facets (SEM) corroborated with previous findings of the wear mechanism of these materials; that is, gold has mainly abrasive wear in contact with porcelain, whereas porcelain has a fatigue type and microfilled resin a tribochemical type of wear. PMID- 8498168 TI - Eye motility dysfunction after soft-tissue injury of the cervical spine. A controlled, prospective study of 38 patients. AB - We investigated eye motility prospectively in 40 patients with a soft-tissue injury of the cervical spine. The initial oculomotor test, performed within 3 months, was pathologic in 8 patients. The follow-up test in 38 patients, on average 15 months after the accident, remained pathologic in the 8 patients and 5 additional patients had changed from normal to pathologic test results. At follow up, all the 13 patients with oculomotor dysfunction had persisting symptoms, while 5 of the 25 cases with normal test results still were symptomatic. PMID- 8498169 TI - Color-coded Duplex sonography of vertebral arteries. 11 cases of blunt cervical spine injury. AB - In 11 patients with locked cervical spine facets after blunt injury, the patency of the vertebral arteries was evaluated by color-coded Duplex sonography (CCDS) up to 11 years after the accident. In 7 patients the dislocations had been reduced, 2 had been treated conservatively, and 9 had been fused. In 9 patients (3 of them with persistent locking) the mean systolic peak flow velocity was 55 cm/sec and the vessel diameter was 0.35 cm. Only 2 patients had an abnormal CCDS. In 1 with persistent locking the ipsilateral vertebral artery was occluded, and in the other flow signals were abnormal and the vessel diameter was smaller than on the contralateral side. The high coincidence of vertebral artery occlusions and locked dislocations, as well as fracture dislocations reported by others, was not confirmed in our series. PMID- 8498170 TI - Anterior square-plate fixation of sacroiliac disruption. 2-8 years follow-up of 23 consecutive cases. AB - 21 consecutive patients with 23 rotationally and vertically unstable sacroiliac joint disruptions were operated on through an anterior approach. Open reduction and internal fixation with a 2-hole square plate was performed. At follow-up after 5 (2-8) years, 18 patients were rated excellent or good and 3 patients poor. In all the cases the reduction of the SI-joints was maintained. PMID- 8498171 TI - Porosity of bone cement reduced by mixing and collecting under vacuum. AB - Palacos R bone cement was mixed in a commercial vacuum mixing system (MITAB), and in an experimental system allowing evacuating air from the powder before mixing and collecting the cement under partial vacuum. The effect on the porosity of mixing at different pressure levels was tested. The effect of evacuating air from the powder before mixing was also analyzed. The numbers and sizes of the voids in the cement samples were measured in radiographs and under the microscope. Also, the density of the cement was measured. Vacuum mixed samples had a substantial reduction of voids, as well as an increase in density compared to mixing at atmospheric pressure. After vacuum mixing and collection, a further reduction of the porosity and increased density were seen; all the large voids within the cement were eliminated at 0.05 bar absolute pressure. PMID- 8498172 TI - The external fixation test of the lumbar spine. 30 complications in 25 of 100 consecutive patients. AB - We retrospectively analyzed the rate and character of complications in a series of 100 consecutive external fixation tests during 1985-1991. There were 30 complications in 25 patients. The most common was pin tract infection, which was definite in 12 cases and probable in 6. Although 12 patients developed complications that resulted in removal or reapplication of the device. 8 cases had an incorrect position of a Schanz screw; 3 of these had neurological complications. The only variable having a significant association with complications was the duration of the test. Because of this complication rate, the indications for the test should be carefully considered. PMID- 8498173 TI - 9 Knee arthroplasties for sickle cell disease. AB - Sickle cell disease sometimes presents with knee arthropathy secondary to osteonecrosis. We report our experience with 9 total knee arthroplasties in 5 patients. The joint fluid, synovium, capsule, and excised bones were sent for culture. Tissue cultures from 5 knees grew organisms. The outcome was: 6 excellent, 1 good, 1 satisfactory, and 1 poor. Infection in 1 case led to removal of the prosthesis and subsequent arthrodesis. 1 patient had persistent peroneal nerve palsy. There were no hematological complications. We suggest that osteonecrosis in sickle cell disease should be considered septic. PMID- 8498174 TI - Knee arthroplasty in hemophilia. 5-12 year follow-up of 15 patients. AB - Between 1979 and 1987, 15 knee arthroplasties were performed in 15 Norwegians with congenital disorders of blood coagulation. 10 patients with a median follow up of 7 (5-12) years had an almost painless joint, without hemorrhage. Flexion contractures were corrected, but total range of motion was not improved. There was a radiolucent zone at the bone-cement interphase of the tibial stem in 2 knees. The placement of the implants was correct and the alignment not changed. There were no fractures. 1 prosthesis had been removed because of a chronic infection. 4 patients had died. We conclude that arthroplasty can be safely performed with excellent relief of pain and improvement of function in patients with congenital disorders of blood coagulation. PMID- 8498175 TI - Muscle contribution to tibial fracture strength in rats. AB - We studied the contribution of anesthetized and dead muscle to the loading capacity of the tibia in ventral three-point cantilever bending directly by a newly developed method in rats. Ketamine anesthesia, known to give poor muscle relaxation, did not increase the loading capacity more than Hypnorm/Dormicum anesthesia and dead muscle. The ultimate bending moment increased by about 40 percent and the ultimate absorbed energy by about 85 percent when the tibia was tested in situ compared to testing in the dissected state; the tibia could withstand approximately 50 percent more deflection when loaded intact with soft tissues. No differences were observed between the tibia of anesthetized and newly killed rats. The results indicate that the soft tissues are quantitatively important for the strength of long bones, and for the understanding and prevention of fractures. PMID- 8498176 TI - Surgery for fracture of the calcaneus. 5 (2-8) year follow-up of 20 cases. AB - 20 displaced intraarticular fractures of the calcaneus were treated by open reduction and internal fixation. Results were evaluated according to a standardized protocol. With an average follow-up of 5 (2-8) years, results were excellent or good in 15 cases and fair or poor in 5 cases. An accurate radiographic study and CT scanning are essential for understanding these fractures. We feel that restoring calcaneal shape as anatomic as possible, getting an appropriate reduction of the posterior joint surface by a surgical procedure with early mobilization, and delayed weight bearing would be a good option in treatment of these fractures. PMID- 8498177 TI - Prevalence of coxarthrosis in former soccer players. 286 players compared with matched controls. AB - We compared the occurrence of coxarthrosis in 286 male former soccer players in Malmo with a mean age of 55 years with an age-matched control group. During the last decades about one fifth in both groups had been referred to hip radiography. Coxarthrosis occurred in 5.6 percent of the former soccer players and in 2.8 percent of the control group (P 0.04). Among the 71 elite soccer players the prevalence of coxarthrosis was 14 percent compared with 4.2 percent in age matched controls and non-elite players. Elite soccer players apparently run an increased risk of developing coxarthrosis. PMID- 8498178 TI - Bone mineral normative data in Malmo, Sweden. Comparison with reference data and hip fracture incidence in other ethnic groups. AB - The bone mineral mass was measured in 324 residents of the city of Malmo, Sweden, by dual energy roentgen absorptiometry (DEXA) using the Lunar DPX equipment- total body, hip, and lumbar vertebrae. The bone mineral content of the wrist was also measured with single photon absorptiometry (SPA) in 88 of the individuals. Weight, height, and vertebral height, as well as body fat, lean body mass, menarcheal age, menopausal age, and hand grip strength were determined. Measurements were compared with reference bone mineral content values from the United States, Japan, and France--also hip fracture incidence was compared. All bone mineral values decreased with age. A good correlation was found between the DEXA technique of total body bone mineral and the forearm SPA values. The bone mineral content was correlated with lean body mass and weight. The Malmo bone mineral content was on the same level as in the United States, but higher than in Japan and France. The comparatively high risk of fragility fractures in the Scandinavian countries compared with most other settings cannot be explained by low bone mass. PMID- 8498179 TI - Changing methods of hip fracture osteosynthesis in Sweden. An epidemiological enquiry covering 46,900 cases. AB - An enquiry covering all hospitals in Sweden operating on hip fractures was conducted in 1990. The results were compared with enquiries from 1982 and 1985. In cervical hip fractures the use of single nail has almost disappeared in favor of 2 LIH hook pins and, lately, the Uppsala subchondral screws. Primary hip prosthesis is the ultimate method of choice in Sweden. Among trochanteric hip fracture the Ender nail has almost totally been replaced by a sliding screw and plate device. PMID- 8498180 TI - Factors predicting healing complications in femoral neck fractures. 138 patients followed for 2 years. AB - We have previously studied the radiographic outcome of femoral neck fracture osteosynthesis with either two hook-pins or a four-flanged nail performed by a small group of surgeons with special interest in the methods. In 138 femoral neck fractures a backwards stepwise logistic regression analysis was used to study the significance of preoperative fracture-related factors, intraoperative factors and the osteosynthesis. The development of non-union/redisplacement and segmental collapse of the femoral head was influenced by fracture displacement (P 0.001) and method of osteosynthesis (P 0.007). The postoperative scintimetric ratio was influenced by the method of osteosynthesis (P 0.0003), fracture displacement (P 0.004) and by the presence of a posterior fragment (P 0.03). Reduction of the fracture and positioning of the osteosynthesis were to a large extent within the accepted limits. This may explain why the previously well documented negative effects of malpositioning of the osteosynthesis and inferior reduction were not demonstrated to influence the rate of healing-complications. We conclude that neither patient age, sex nor preoperative fracture variables, with the exception of the extent of fracture displacement, can be used to predict radiographic healing-complications in femoral neck fractures. PMID- 8498181 TI - Hip fracture incidence in Malaysia 1981-1989. AB - The age-corrected incidence of hip fracture in the city of Kuala Lumpur and the surrounding districts has increased from 1981 to 0.7 per 1,000 population in 1989. Women dominated by a factor of 1.3. The mean age was 73 (50-103) years. The increased rate observed was attributed solely to trochanteric fractures among those 70 years and above. There were differences in the various parameters among the different races. The fracture incidence and woman/man ratio were substantially lower than has been reported from developed countries. PMID- 8498182 TI - Bone and muscle mass after hip arthroplasty. A quantitative computed tomography study in 20 arthrosis cases. AB - We performed a prospective, quantitative computed tomography (QCT) study of bone mineral density (BMD), cortical bone volume, bone mass and muscle volume in 20 patients who were operated on with cemented total hip arthroplasty because of unilateral arthrosis. Both extremities were measured preoperatively, 3 and 6 months after the operation by a single-energy computer tomograph equipped for bone mineral densitometry. Preoperatively, we found a 25 percent decrease in muscle volume of the thigh on the arthrosis side compared to the contralateral side, but only a 6 percent decrease in bone mass, mainly of the cortical bone volume in the middle femur. In the cancellous bone of distal femur and proximal tibia there was a reduction in BMD of 11 and 14 percent, respectively, compared to the contralateral side. After 6 months, we found no changes in cortical bone mass, either on the operated femur or on the contralateral, control femur. The BMD of cancellous bone in distal femur and proximal tibia had not changed. However, the thigh muscle on the operated side showed a strong recovery; 6 months after the operation there was a 19 percent gain on the operated side. PMID- 8498183 TI - Ectopic ossification in hip arthroplasty. A retrospective study of predisposing factors in 637 cases. AB - We investigated predisposing factors for the development of heterotopic ossification in a retrospective study of 637 hip arthroplasties, of which 484 were unilateral, 62 bilateral and 29 revision operations. The frequency of heterotopic ossification after a primary hip arthroplasty was 57 percent. In a univariate analysis, men, patients with hypertrophic arthrosis, and cemented arthroplasty were all at risk of developing heterotopic ossification. After a multivariate analysis, the male sex and the cemented arthroplasty remained as significant factors. In bilateral operations, the contralateral side developed heterotopic ossification in 82 percent when the primary hip operation had already caused ossification. There was no increase in ossifications after the contralateral operation. Half of the revision operations had an increase of heterotopic ossification from 1 to 4 Brooker classes. PMID- 8498184 TI - Open reduction of CDH before one year of age. 69 hips followed for 13 (10-19) years. AB - 50 children (69 hips) had open reduction of congenital dislocation of the hip (CDH) at the age of 7 (2-12) months. 4 hips had a poor result from severe necrosis of the femoral head. Another 5 hips with less severe necrosis had a fair result. 7 of the 9 hips with avascular necrosis were below the age of 6 months at the time of operation. 13 hips (9 children) required complementary operations to establish congruous reduction of the hip. The follow-up period was 13 (10-19) years, and the results were successful in 53 hips. No difference was found in the unilaterally and bilaterally operated on hips. Anteversion corrected itself in due time in most of the hips, and coxa magna had disappeared in hips that had reached maturity. Good hips remained good and poor hips became progressively worse. PMID- 8498185 TI - Late disassembly of modular acetabular components. A report of two cases. AB - We report two cases of late disassembly of modular acetabular components, 4 and 5 years after implantation. One was revised immediately after the disassembly and one after 4 months, the latter demonstrating excessive wear of metal and polyethylene. Radiographs showing eccentric displacement of the femoral head in the cup associated with a dark, curved shadow representing the displaced polyethylene insert identify this type of implant failure. PMID- 8498186 TI - The effect of fracture on femoral head blood flow. Osteonecrosis and revascularization studied in miniature swine. AB - Miniature swine were used to study the effect of cervical fracture on femoral head blood flow. Laser Doppler flowmetry was used to evaluate femoral head blood flow before and after the fracture, after internal fixation with or without compression, and 8 weeks post-fracture. Fluorescent bone-labeling was performed at 2, 4 and 6 weeks post-fracture. Femoral head blood flow decreased to 40 percent of baseline following fracture, partly from the disruption of venous drainage. Histologically, all femoral heads showed some degree of trabecular thinning, microfracture, and neovascularization when compared with controls. Analyses of the laser Doppler flowmetry data, fluorescent label histology, microradiography and bone densitometry indicated that late (4-6 weeks) revascularization produces severe trabecular mechanical weakening and resultant femoral head collapse. Femoral head ischemia following fracture probably falls along a continuum, with only the more severe cases proceeding to mechanical collapse. Femoral neck fractures in the minipig produce femoral head necrosis of a severity and incidence which closely parallels that of the human population; thus, the minipig is a useful model for further study of complications following femoral neck fracture in humans. PMID- 8498187 TI - Acute effects of intramedullary reaming on bone blood flow in rats. AB - We examined the acute effects of increasing degree of intramedullary reaming on bone blood flow in 27 male Wistar rats by use of the microsphere method. A marginal reduction in total bone and cortical bone blood flow was seen when the femoral canal was reamed to a diameter smaller than the medullary cavity (1.5 mm). Reaming equal to the antero-posterior diameter (1.8 mm) halved total bone flow and reduced cortical blood flow by one third. Reaming equal to the transverse diameter (2.1 mm) reduced total bone flow to one third and cortical bone flow by one third. Intramedullary reaming of the tibia to 1.5 mm reduced total blood flow about 50 percent whereas cortical flow in the proximal half was unchanged. We conclude that modest intramedullary reaming has little effect on total and cortical blood flows, whereas reaming which involves destruction of the endosteal cortex reduces both total bone and cortical blood flows. PMID- 8498188 TI - Radial osteotomy for Kienbock's disease evaluated by magnetic resonance imaging. 24 cases followed for 1-3 years. AB - 24 patients with Kienbock's disease were followed with magnetic resonance imaging (MRI) for 1-3 years. 9 patients were treated with radial shortening, 10 with radial wedge osteotomy and 5 patients were treated non-operatively. Signal intensity of the lunate on T1-weighted or T2-weighted images increased postoperatively in all operated on patients, and normal or near-normal signal intensity was observed in 9 patients on T1-weighted images and in 15 patients on T2-weighted images postoperatively. Signal intensity did not increase in any patient treated non-operatively. The postoperative increase in signal intensity on MRI following radial shortening and radial wedge osteotomy presumably is due to revascularization of the lunate. PMID- 8498189 TI - Radiographic assessment of component orientation in elbow arthroplasty. A technical description. AB - We describe an alternative method of taking standardized radiographs of the elbow in patients with rheumatoid arthritis, taking into account fixed deformities. The technique enables assessment of the orientation of joint replacement components, including their axial rotational alignment. The accuracy of the method for calculating axial rotational alignment has been evaluated using a skeleton model. Within the 20 degrees limits of arm position the accuracy was found to be on average 1.4 degrees for the humerus and 2.2 degrees for the ulna. PMID- 8498190 TI - Enthesopathy as the presenting feature of X-linked hypophosphatemia. A case report. AB - X-linked hypophosphatemia has a wide spectrum of clinical presentation. I describe a woman in whom diffuse enthesopathy was the only manifestation. The diagnosis was established from the family history. The severity of the enthesopathy did not relate to the severity of the biochemical changes. PMID- 8498191 TI - Irreducible antero-medial dislocation of the radius. A case of biceps tendon interposition. PMID- 8498192 TI - Excision of the scaphoid bone. A case report with 7-year follow-up. PMID- 8498193 TI - Mineral and mechanics of bone fragility fractures. A review of fixation methods. PMID- 8498194 TI - Undisplaced femoral neck fracture. To operate or not to operate? PMID- 8498195 TI - Prelogical relics in language development. PMID- 8498196 TI - Language families. AB - The "genetic" relatedness of languages and their grouping into "families" is a metaphor taken from biology. The family tree model fails to account for the mutual influence of languages; hence the "wave" theory. Family relationships are set up by systematically recurring phonetic differences, rather than similarities. The 4,000 languages are grouped in about 50 language families:linguistics tries to find their common features, called "language universals". PMID- 8498197 TI - Functional anatomy of human speech. AB - The outlines of an investigation into side differences between the Planum temporale (The Geschwind-Levitzky areas) of ten human brains are given. Volume of this area and cell numbers are clearly asymmetric, the left side being consequently larger by 38-34% over the same area at right. Cell density (cell No/volume) is virtually the same on both sides. Some comments upon the data are being made. PMID- 8498198 TI - Cortical DC-potentials in identification of the language-dominant hemisphere: linguistical and clinical aspects. AB - In order to find a non-invasive method for determining the hemispheric dominance for language, we studied cortical activation patterns during language processing by means of electrophysiological techniques: DC-potentials were recorded from frontal, central, temporal and parietal electrode positions in 28 right-handed normal subjects and in 16 patients with a history of transient loss of speech and known hemispheric dominance. Subjects were asked to find as many synonyms as possible within 6 seconds to either a concrete or an abstract noun. This task caused a highly significant left-hemispheric lateralization over frontal and central, but not over temporal and parietal cortical areas. Search for synonyms to abstract nouns yielded frontal left-hemispheric dominance in 93% of all normal subjects, search for synonyms to concrete nouns in 85%. Inter-electrode correlation coefficients were higher during processing of abstract word categories than during processing of concrete categories. In all patients, frontal and central lateralization corresponded to their hemispheric dominance as determined from clinical data. Advantages as well as inconveniences of this technique are discussed and compared to other invasive and noninvasive tools of assessing speech lateralization. PMID- 8498199 TI - Brain mapping in thinking and language function. AB - Regional cerebral blood flow, rCBF, is coupled to regional cerebral metabolism and changes in rCBF reflects changes in neuronal activity. rCBF studies have provided information about the functions of a great number of cortical regions in the normal human brain. Outside the motor areas and sensory association areas there are areas committed to the transformation of information retrieved or generated within the brain itself. Language is processed within these regions. In contrast to the general clinical impression the functional mapping methods reveal that there is a large number of cortical regions activated bilaterally during language processing. Pure intrinsic brain work causes a profound activation of the cerebral cortex. Different types of thinking are seen to activate different sectors of the cortical space. PMID- 8498200 TI - The effects of electrostimulation and of resective and stereotactic surgery on language and speech. AB - A fairly comprehensive survey is offered of the effects which cortical and sub cortical electrical stimulation have on language and speech. A survey is also given of the verbal consequences of resections or coagulations which generally follow electrical stimulation. PMID- 8498201 TI - Clinical forms of aphasia. AB - A survey is given on the history of knowledge of aphasia and on the necessity and possibilities of classification of aphasic disability. Also the association of clinical syndromes of aphasia with particular damage to the brain is outlined. For Wernicke's aphasia (fluent aphasia with comprehension deficit) a superior posterior temporal lesion is obligatory. The persistent jargon aphasia is associated with a lesion of the supramarginal gyrus. Broca's aphasia is seen with posterior inferior frontal lesions, but additional central and subcortical components are involved in persisting deficit. The lesions producing transcortical motor aphasia involve the supplementary speech area of Penfield. Transcortical sensory aphasia is related to lesions that overlap the watershed area between the middle cerebral and the posterior cerebral arteries. PMID- 8498202 TI - Aphasia in bilinguals. AB - The neurophysiological and the neurolinguistic basis of multilingualism is not yet fully elucidated. A study of the occurrence of aphasia in multilingual patients and the pattern of recovery may help to clarify some unsolved problems. For e.g. is the ability to use a second language stored in a different area of the left hemisphere and what is the extent of involvement of the right hemisphere in language skills? When recovery from aphasia occurs, what factors determine the rate of recovery of different languages and the priorities of recovery? To understand some of the problems, a study of aphasia in multilinguals was conducted in Madras, South India, where multilingualism is common. 88 patients were studied with 40 healthy controls, using standard protocols. It was found that the pattern of recovery was dispersed widely in time, rate, level, degree and between the languages known. No support was obtained for the notion that the patients' mother tongue recovers first, nor was support found for the importance of language proficiency viewed globally. Evidence was found that the languages in which routine thinking, mental calculations and praying were carried out were the ones most resistant to damage in brain insults. It is interesting that these functions are all highly overlearned, acquired early in life and used frequently over the course of many years. Another observation made was that the incidence of crossed aphasia was fairly high, in both uni- and multi-linguals, with the latter showing a slightly higher incidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498203 TI - The role of music and song in human communication. AB - It is only on the higher level of abstraction and generalization that the two human branches of acoustic communication, speech and music are separated from each other. Speech is primarily adjusted to the conceptual-verbal symbols and representation of an objectified, static world. In the linguistic communication the main role is played by the elements of noise, the consonants. It has never been doubted that music is a kind of communication, the mediator of human relationships, but it has been a question what music wants to express. Since the Pythagoreans, some believe to find the key to interpreting its message in the commun quantifiable nature of the musical medium and the cosmos. Another historical tradition considered music as the direct expression of human emotions. Representants of the doctrine of imitation derived music from the intonation of speech and the text seems for many to be a support to "understand" music. Music separated from the primary source of sound phenomena and their direct sensual effect constructed a specific communication system. It possesses an inestimable potential richness of discrete pitches and times, colours and sound intensity. The infinite potentials of successive and simultaneous combinations are suitable for erecting the audible, dynamic models of human relations and types of behaviour, internal events and interactions, different situations. European polyphony established a strictly regulated, closed syntax of musical communication which comes close to conceptual precision. Its logic is based upon the natural potentials of the kinship of pitches and the human organ of hearing. The live, mobile network of the relations thus created is regulated by a further developed quasi-binary logic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498204 TI - Operations on gliomas involving speech centres. AB - One hundred patients with gliomas of the dominant hemisphere, who survived for more than one year after operation, have been analysed. In all of them radical tumour removal had been attempted. Already preoperatively 58 of them had signs of speech deficit. Postoperatively 65% improved and only 15% deteriorated with regard to their speech function. Therefore it seems not to be justified to deny operative tumour removal to patients with gliomas located within or near the speech areas. PMID- 8498205 TI - The surgery for epilepsy with speech arrest. AB - The problems confronting patients with epilepsy, their families, and the surgeons wishing to help such patients, are discussed. It is important for physicians in other specialties to realize that epilepsy surgery is not nowadays complex, difficult, painful or uncertain; furthermore such operations are based on finding and removing focal lesions rather than "epileptogenic cortex" and the result in terms of integration of the patient into society is much improved if such intervention is performed while the patient is young, with time to gain academic and social skills after the operation. The selection of patients suitable for operation is discussed as well as methods of determining which hemisphere is dominant for speech and whether or not the focal lesion involves language centres. The majority of patients with drug resistant epilepsy suitable for operation have abnormalities in one temporal lobe. The pathological lesion is described and the advantages and disadvantages of various operations for temporal lobe epilepsy discussed. Extra-temporal cortical resection in the dominant hemisphere is also considered, particularly with reference to the preservation of language function. It is important that neurosurgeons realise that MRI and CT scanning have transformed epilepsy surgery from being a rather nebulous, time consuming art, to being for the majority of patients, a clear cut, straight forward procedure firmly based on "Oslerian" pathological principles. Far too few patients are being offered an operation (which renders 60-70% seizure free); neurosurgeons should respond to this challenge. PMID- 8498206 TI - Lateralisation of speech centre in left-handedness due to cerebral and extracerebral lesions. AB - This report is based on a study of a small sample of five patients who were initially right-handed and became left-handed due to loss of function in the right arm after extracerebral causes such as polio or injury. Carotid amytal tests in these patients showed that all of them still had the speech centre in the left hemisphere. As expected, lateralised neuropsychological brain function tests showed no significant differences between right and left brain. In infantile right hemiplegia due to atrophic left brain lesions, the speech centre had shifted to right side in 10 out of 15 patients. Neuropsychological tests showed sparing and protection of dominant left brain functions. PMID- 8498207 TI - Psychological mechanisms of speech rehabilitation in aphasic patients. AB - The theoretical basis of speech rehabilitation and some inherent mechanisms of language/speech, that could be used to overcome speech disorders, are discussed. Among them: Stimulation of speech functions of the right hemisphere, structures of functional systems according to Luria, modular systems in cognitive neuropsychology, and the importance of the use of new processing strategies. PMID- 8498208 TI - Communication in animals. AB - The paper deals with the antecedents of human speech in animals, more precisely with the problems of continuity versus discontinuity in communication between the different species of vertebrates. It puts emphasis on higher classes of mammals, namely monkeys and apes. Three ancient structures and mechanisms are listed which may have a role as forerunners of the development of human speech: (1) the activity of the mimic muscles of the cheeks and of the jaws, (2) the evolution of sound-producing specialized membranes in the laryngeal respiratory passages, and (3) the development of hemispheric asymmetries of the brain, which culminated in the emergence of the specific speech areas of the dominant hemisphere in humans. The history of the research of animal language cannot avoid the survey of the fascinating trials made on anthropoid apes. The paper briefly summarizes the four approaches (American Sign Language, plastic tokens, keyboard systems and mimics) with the conclusion that continuity can be demonstrated in brain lateralization and in cognitive abilities, but a marked discontinuity between animal communication and human speech is evident. PMID- 8498209 TI - Features of computer language: communication of computers and its complexity. AB - Motivated by computer science, in particular, by applications to data security, electronic correspondence and cryptography, interactive proofs extend the 2000 years old, well established notion of mathematical proof. The key to these development is complexity which is defined as the minimum amount of a certain resource needed to complete a computational task. In this paper, the idea of an interactive proof system and its application in computer science is illuminated on everyday examples, without giving technical details. PMID- 8498210 TI - Computer and the thought process. AB - Modelling of brain is an eternal problem and was revitalized by arrogant claims of some computer scientists. Several basic results of mathematics, especially in problems of uncertainty, computational complexity and logic prove limits of computation and indications that the brain works otherwise. The complexity of brain is not accessible by current electronic technology. However, brain research and computer science can learn a lot from each other by revealing relevant analogies. PMID- 8498211 TI - Beaumont and St. Martin. PMID- 8498212 TI - MR imaging to detect chest wall and pleural involvement in patients with lymphoma: effect on radiation therapy planning. AB - OBJECTIVE: The purpose of this study was to determine the influence that accurate MR detection of chest wall and pleural disease has on the type and extent of radiation therapy subsequently performed in patients with thoracic lymphoma. MATERIALS AND METHODS: MR images and CT scans of the chests of 57 patients who had biopsy-proved lymphoma were retrospectively examined for evidence of involvement of the chest wall and pleura. For patients with thoracic lymphoma, we compared radiation portals and dosage designed by using information from MR images with portals and dosage designed by using information from chest radiographs and CT scans. RESULTS: Chest wall or pleural disease was detected in 22 of the 57 patients examined. Chest wall disease was identified on MR images in 20 patients (29 sites) and pleural disease in 14 patients (16 sites). Chest wall and pleural disease were identified on CT scans in seven and five patients, respectively. Of the 15 patients who received radiation therapy, three (20%) had treatment planning altered, either by increasing the area exposed to radiation or by increasing the radiation dose, because of findings noted only on MR images. CONCLUSION: Chest wall and pleural sites of disease that may be detected only on MR images can be important in designing appropriate radiation portals and dosage for patients who have chest lymphoma. PMID- 8498213 TI - Tumefactive Pneumocystis carinii infection in AIDS: report of three cases. PMID- 8498214 TI - Coexistent intralobar and extralobar pulmonary sequestration: imaging findings. PMID- 8498215 TI - Superficial thrombophlebitis of the breast (Mondor's disease): mammographic findings. PMID- 8498216 TI - Sonography in AIDS-related cholangitis: prevalence and cause of an echogenic nodule in the distal end of the common bile duct. AB - OBJECTIVE: The purpose of this study was to determine the prevalence and cause of an echogenic nodule in the distal end of the common bile duct seen on sonograms in patients who have AIDS-related cholangitis. SUBJECTS AND METHODS: Sonograms of the liver and bile ducts were obtained in 15 patients who had AIDS-related cholangitis. Both 3.75- and 5-MHz transducers were used in all patients. The appearance of an echogenic nodule in the distal end of the common bile duct was compared with the results of endoscopic retrograde cholangiograms in 12 patients and with biopsies of the papilla of Vater in the first five cases. RESULTS: Sonograms showed a hyperechoic nodule in the distal end of the common bile duct in 10 of the 15 cases. Visualization was improved after oral administration of water. The finding correlated with edema of the papilla of Vater noted on retrograde cholangiograms in eight cases. Biopsy of the papilla of Vater in five cases showed an inflammatory infiltrate. The nodule became smaller in one patient when cholestasis improved after treatment for cryptosporidiosis. CONCLUSION: An echogenic nodule was detected in the distal end of the common bile duct on sonograms in two thirds of patients who had AIDS-related cholangitis. Our findings suggest the abnormality is caused by edema of the papilla of Vater. PMID- 8498217 TI - Routine operative cholangiography during laparoscopic cholecystectomy: feasibility and value in 107 patients. AB - OBJECTIVE: Laparoscopic cholecystectomy is becoming a popular alternative to open cholecystectomy. However, the technical aspects of this new procedure increase the risk of injuring the bile ducts. The purpose of this study was to determine the feasibility and value of performing cholangiography during laparoscopic cholecystectomy. MATERIALS AND METHODS: We retrospectively reviewed the clinical and operative cholangiographic findings of the first 107 patients undergoing laparoscopic cholecystectomy at Hotel-Dieu de Montreal between August 1990 and August 1991. RESULTS: Operative cholangiography was attempted in 98% of patients; the success rate was 71%. Eight anatomic anomalies of the biliary tract that were of surgical importance were found as well as 10 cases of stones in the common bile duct, eight of which were unsuspected. No biliary tract injuries occurred. With experience, surgical cannulation of the cystic duct for injection of contrast material can be done quickly without major difficulty, and cholangiograms of excellent diagnostic quality can be obtained. CONCLUSION: Our results show that operative cholangiography is feasible and useful in patients undergoing laparoscopic cholecystectomy. PMID- 8498218 TI - CT arterial portography of the abdomen: effect of injecting papaverine into the mesenteric artery on hepatic contrast enhancement. AB - OBJECTIVE: The purpose of this study was to determine the effect of precontrast injection of papaverine hydrochloride into the superior mesenteric artery on the degree of contrast enhancement of the hepatic parenchyma during CT arterial portography (CTAP, CT with injection of contrast material into the superior mesenteric artery). SUBJECTS AND METHODS: Twenty-two patients were included in this study. All patients had a baseline unenhanced CT scan and then had CTAP performed with transcatheter injection of 150 ml of nonionic iodinated contrast material (30 g iodine/100 ml) at a rate of 2 ml/sec. Eleven patients received a precontrast injection of 40 mg of papaverine hydrochloride via catheter into the superior mesenteric artery, and 11 patients had CTAP without papaverine hydrochloride. Attenuation of the liver was measured before and after contrast administration in both groups of patients. For each CTAP section, the absolute hepatic enhancement (postcontrast attenuation--precontrast attenuation) and the relative hepatic enhancement ([absolute hepatic enhancement/precontrast attenuation] x 100) were calculated. Also, the mean absolute enhancement and the mean relative enhancement for the entire liver were calculated for each patient. RESULTS: The mean relative enhancement (+/- SD) of hepatic parenchyma was 192 +/- 54% with papaverine hydrochloride and 146 +/- 26% without papaverine hydrochloride. Relative enhancement was significantly higher when papaverine hydrochloride was used (p < .02). The mean absolute enhancement (+/- SD) of hepatic parenchyma was 123 +/- 25 H with papaverine hydrochloride and 91 +/- 19 H without papaverine hydrochloride. Absolute enhancement was significantly higher in patients who had papaverine hydrochloride (p < .01). CONCLUSION: The results show that precontrast transcatheter infusion of papaverine hydrochloride increases the degree of contrast enhancement of the liver during CTAP. PMID- 8498219 TI - The first radiology journals. PMID- 8498220 TI - Delayed leaks and fistulas after esophagogastrectomy: radiologic evaluation. AB - OBJECTIVE: Although breakdown of the esophagogastric anastomosis often occurs as a complication of esophagogastrectomy during the early postoperative period, it is not well recognized that anastomotic leaks and fistulas may occur during the late postoperative period (more than 1 month after surgery). The purpose of our study was to determine the radiologic appearance and clinical significance of these late leaks and fistulas. MATERIALS AND METHODS: A review of radiology records at our hospital from 1985 to 1991 revealed 37 patients who had upper gastrointestinal contrast studies an average of 13.3 months after esophagogastrectomy. RESULTS: Six patients (16%) had anastomotic leaks or fistulas that occurred during the late postoperative period. Four patients were asymptomatic; three had contrast studies that showed thin, blind-ending tracks extending from the anastomosis into the mediastinum, and the fourth had an esophagogastric fistula. One of the blind-ending tracks later progressed to a gastropleural fistula that was treated with antibiotics and drainage. One symptomatic patient had a gastropleural fistula, and the other had a gastrobronchial fistula. Both fistulas were surgically repaired. None of the leaks or fistulas was associated with recurrent tumor. CONCLUSION: Anastomotic leaks or fistulas may be detected on contrast studies obtained more than 1 month after esophagogastrectomy. Some leaks appear as blind-ending tracks that have no clinical significance, but others may be manifested by life-threatening gastropleural or gastrobronchial fistulas that necessitate surgical intervention. PMID- 8498221 TI - Duodenal injuries caused by blunt abdominal trauma: value of CT in differentiating perforation from hematoma. AB - OBJECTIVE: Traumatic duodenal perforation requires emergent surgery, whereas duodenal hematoma can often be treated nonsurgically. We assessed the CT findings in patients with blunt duodenal trauma to determine if CT can be used to differentiate these two duodenal injuries. MATERIAL AND METHODS: Seven consecutive patients with blunt duodenal trauma (three with perforation, four with hematoma) who underwent CT as part of their initial diagnostic evaluation were included in the study. All three perforations and one of four hematomas were surgically proved. Diagnoses of duodenal hematoma in the other three patients were based on typical features on upper gastrointestinal studies and complete resolution of clinical findings after conservative treatment. The CT scans were retrospectively reviewed without knowledge of the specific type of duodenal injury, and the findings were correlated with the results of the gastrointestinal studies and surgical findings. RESULTS: CT showed extraluminal gas or extravasated oral contrast material or both in the right anterior pararenal space in all three patients with duodenal perforation and in none of the patients with duodenal hematoma. Thickening of the duodenal wall and fluid in the right anterior pararenal space were seen in both groups of patients. CONCLUSION: Although the number of patients in the study was small, the results suggest that CT may be useful in differentiating duodenal perforation from hematoma without perforation. Extraluminal gas or extravasated oral contrast material or both were seen in the right anterior pararenal space in all three patients who had perforation and in none of the patients who had hematoma alone. PMID- 8498222 TI - Transvaginal color Doppler sonography of adnexal masses: differences in blood flow impedance in benign and malignant lesions. AB - OBJECTIVE: The purpose of this study was to assess the blood flow characteristics of adnexal masses before surgical excision and to determine whether color flow Doppler sonography is useful for distinguishing benign from malignant masses. SUBJECTS AND METHODS: Thirty-one adnexal masses were evaluated with color flow Doppler transvaginal sonography. The pulsatility index and resistive index were calculated from the waveforms generated from blood flow within the ovary. Twenty five lesions were benign and six were malignant on pathologic examination. Benign lesions included six endometriomas, six mesothelial cysts, three serous and one mucinous cystadenoma, three mature cystic teratomas, two hemorrhagic corpus luteum cysts, one cystadenofibroma, one sclerosing stromal cell tumor, one paratubal cyst, and one ovary that had undergone torsion with infarction. The malignant lesions consisted of three papillary serous cystadenocarcinomas, one granulosatheca cell tumor, one immature teratoma, and one metastasis of colon cancer to the ovaries. RESULTS: Benign tumors and cysts had a significantly higher pulsatility index (mean, 1.93 +/- 1.02; range, 0.23-3.99) and resistive index (mean, 0.77 +/- 0.22; range, 0.2-1.0) than did malignant tumors (pulsatility index: mean, 0.77 +/- 0.33; range, 0.31-1.09; resistive index: mean, 0.5 +/- 0.17; range, 0.27-0.67). However, some overlap in individual values for benign and malignant lesions was found. CONCLUSION: Our preliminary data suggest that high pulsatility and resistive indexes indicate benign adnexal processes; however, considerable overlap in pulsatility and resistive indexes between benign and malignant lesions was noted, and further work is needed before the validity of these factors is proved. PMID- 8498223 TI - MR imaging in the diagnosis of rare forms of ectopic pregnancy. PMID- 8498224 TI - MR evaluation of the anterior cruciate ligament: value of supplementing sagittal images with coronal and axial images. AB - OBJECTIVE: Most studies evaluating the anterior cruciate ligament have focused on sagittal MR images for the diagnosis of injury. Limitations of sagittal images have been reported, however, including nonvisualization and incomplete visualization of the ligament. This study was undertaken to assess the value of adding coronal and axial MR images to sagittal images in the evaluation of the anterior cruciate ligament. MATERIALS AND METHODS: We reviewed oblique sagittal T1-weighted, coronal T2-weighted, and axial T2-weighted images to determine the status of the anterior cruciate ligament in 325 patients. All patients had arthroscopy. Sagittal images were initially interpreted alone and then in combination with coronal and axial images. RESULTS: Sagittal T1-weighted images alone had a 94% sensitivity and an 84% specificity for determining the status of the anterior cruciate ligament. A multiplanar evaluation of the anterior cruciate ligament resulted in a change in MR interpretation in 21 patients (6%), which led to an improved sensitivity of 98% and a specificity of 93%. Diagnostic confidence was improved in an additional 14 patients (4%). CONCLUSION: Our results show that the efficacy of MR imaging for the detection of anterior cruciate ligament tears is greater when axial and coronal images are used in combination with sagittal images than when sagittal images are used alone. PMID- 8498225 TI - Lack of correlation between site of wrist pain and location of noncommunicating defects shown by three-compartment wrist arthrography. AB - OBJECTIVE: Communicating defects shown by wrist arthrography often correlate poorly with the location of the patient's symptom(s). No study of wrist arthrography in which noncommunicating defects have been isolated, described, and correlated with the site of patients' symptoms has been reported. The aim of this study was to correlate the site(s) of patients' pain and the location(s) of noncommunicating defects shown by wrist arthrography. MATERIALS AND METHODS: One hundred noncommunicating capsular defects and incomplete defects of the interosseous ligaments and triangular fibrocartilage in 82 patients were identified from 462 three-compartment wrist arthrograms. Correlation between the sites of pain and sites of the noncommunicating defect was described as: (1) exact correlation, (2) ulnar/radial side correlation, (3) ambiguous correlation, or (4) no correlation. Statistical analysis was performed for each type of defect separately, in aggregate for patients who had more than one defect, and by separate analysis using patients' age (less than or greater than 30 years old). RESULTS: Capsular defects were detected in 65 patients, incomplete perforations of the triangular fibrocartilage in 28 patients, and incomplete defects of the scapholunate and lunotriquetral ligament in three patients each. No statistically significant correlation was found between individual defects and symptoms or between the site(s) of symptoms and patterns of multiple noncommunicating defects. Further, age did not influence the degree of correlations (chi 2 = 0.000 0.476, p values = 0.49-1.00). CONCLUSION: Attribution of patient's symptoms to noncommunicating defects shown by wrist arthrography is not reliable. Cases in which site-specific arthrographic defects directly correlate may be fortuitous. Additional studies will be necessary to determine the future role of wrist arthrography in the evaluation of the painful wrist. PMID- 8498226 TI - Sequestra in primary lymphoma of bone: prevalence and radiologic features. AB - OBJECTIVE: Our objective was to determine the prevalence and spectrum of radiologic features of sequestra (detached pieces of bone separated from the involved segment) in cases of primary lymphoma of bone. This is a feature of primary lymphoma of bone that, to our knowledge, has not been reported previously. Recognizing sequestra is important, because a limited differential diagnosis of entities exists when this finding is seen. MATERIALS AND METHODS: We retrospectively reviewed all the clinical and pathologic information and radiologic studies in our archives on 434 cases of skeletal lymphoma. Of these, 246 met our criteria for consideration as cases of primary lymphoma of bone. All cases were pathologically proved. Plain radiographs were available for review in all cases, and CT scans were available in 46. Data on the presence or absence of sequestra, their size and appearance, the bone involved, and the site of involvement were recorded in each case. RESULTS: Sequestra were noted in 28 (11%) of the 246 cases. The size varied from 2 to 45 mm (average, 12 mm), and multiple sequestra were seen in 17 cases. They were seen in the long bones (15 cases), axial skeleton (10 cases), and three other sites (scapula, calcaneus, and third metatarsal). CONCLUSION: Sequestra have been reported in a variety of conditions, including osteomyelitis, eosinophilic granuloma, fibrosarcoma, malignant fibrous histiocytoma, and desmoplastic fibroma. Because sequestra were seen in 11% of the cases of primary lymphoma of bone reviewed in this study, we believe that lymphoma should also be included in the differential diagnosis when a sequestrum is noted on imaging studies. PMID- 8498227 TI - Enthesopathy associated with seronegative spondyloarthropathy: 99mTc-methylene diphosphonate scintigraphic findings. PMID- 8498228 TI - Sonography of the fetal heart: normal variants and pitfalls. AB - Sonographic evaluation of the fetal heart is an important part of obstetric sonography. The sonographer and sonologist should be familiar with the sonographic appearance of the normal fetal heart and with common structural abnormalities. Occasionally, normal structures in or adjacent to the fetal heart may simulate an abnormality. Although one should seek consultative sonography in instances of uncertain or questionable findings, unnecessary referral and concern may be avoided in some cases if the sonologist is familiar with normal variants and pitfalls. In this pictorial essay, we present several such pitfalls that we and others have observed in the four-chamber view (Fig. 1) and in views of the ventricular outflow tracts (Figs. 2 and 3). PMID- 8498229 TI - Abnormalities of the posterior inferior cerebellar artery: MR imaging findings. AB - The purpose of this essay is to review the normal MR appearance of the posterior inferior cerebellar artery (PICA) and to illustrate the MR findings of representative PICA abnormalities. Because of beam-hardening artifacts, the lower posterior fossa is difficult to evaluate with CT. MR imaging is not hampered by these artifacts. Moreover, the superb sensitivity of MR and its multiplanar imaging capability permit excellent diagnostic accuracy in this region. The PICA is well suited for evaluation on routine MR images, particularly because of the inherent contrast (signal void) of large arteries due to rapid flow. MR imaging has greatly improved our ability to noninvasively diagnose abnormalities of cerebral blood vessels and their resultant manifestations. Some of the diseases that affect the PICA include neoplasms, aneurysms, arteriovenous malformations, and occlusions. The MR images in this essay illustrate the normal appearance of the PICA, as well as these pathologic features. T1-weighted (e.g., 600/15 [TR/TE]), proton density-weighted (e.g., 2000/20), and T2-weighted (e.g., 2400/80) MR images were obtained in axial, sagittal, and coronal planes. The PICA can be evaluated with MR angiography also, although the relatively small size and tortuosity of the artery may preclude adequate visualization. PMID- 8498230 TI - Embolization of a dural sinus fistula by direct puncture of the occipital arteries. PMID- 8498231 TI - Diagnosis of carotid artery disease: preliminary experience with maximum intensity-projection spiral CT angiography. AB - OBJECTIVE: Spiral CT allows continuous data to be acquired rapidly, and if a correctly timed IV bolus of contrast material is given, spiral CT angiography can be performed. This study was designed to evaluate spiral CT angiography with maximum-intensity-projection reconstructions for assessing the degree of carotid artery stenosis. SUBJECTS AND METHODS: Spiral CT angiography (of 28 carotid bifurcations in 14 patients) was compared in a blinded fashion with conventional angiography (of 28 bifurcations) and with two-dimensional time-of-flight MR angiography (of 12 bifurcations) to assess degree of stenosis. A nonblinded comparison of the contour of the lumen at the site of stenosis was then made between conventional angiography, spiral CT angiography, and MR angiography. The degree of stenosis was measured in each internal carotid artery and categorized as mild (< 30%), moderate (30-69%), or severe (70-99%) stenosis or as occlusion. Maximum-intensity-projection images were used for the evaluations; however, if calcification was circumferential and the lumen of the carotid artery could not be analyzed in the area of the calcification, the axial source images were used. RESULTS: The results of CT angiography and conventional angiography agreed overall in 25 (89%) of 28 cases (r = .921, p = .05, Spearman rank correlation). The presence of severe stenosis or occlusion was correctly identified in seven of seven cases. In the moderate and mild stenosis categories, 18 (86%) of 21 were correctly identified (r = .802, p = .122). Three internal carotid arteries (11%) had circumferential calcification that necessitated evaluation of the axial source images, and the measurements obtained from the axial images agreed well with angiographic findings. MR angiography correlated well with the various categories of stenosis. However, when we compared MR angiography directly with CT angiography and conventional angiography, we found that the degree of stenosis was overestimated when MR angiography was used. CONCLUSION: Our results show that spiral CT angiography shows normal and abnormal carotid anatomy well when compared with conventional angiography. The short examination time and clear depiction of arterial caliber in areas of stenosis are significant advantages of spiral CT angiography compared with MR angiography. PMID- 8498232 TI - Pleomorphic xanthoastrocytoma. PMID- 8498233 TI - Spiral CT angiography. AB - Spiral CT angiography is a new, minimally invasive technique for vascular imaging that is made possible by combining two recently developed techniques: slip-ring CT scanning and computerized three-dimensional (3D) reconstruction. The purpose of this essay is to illustrate the appearances of various normal and diseased vessels using this technique. PMID- 8498234 TI - Phlegmasia cerulea dolens: treatment by pulse-spray and infusion thrombolysis. PMID- 8498235 TI - Femoral hernia simulating a pseudoaneurysm on color Doppler sonography. PMID- 8498236 TI - An interactive, computer-based atlas of neurologic positron emission tomographic studies for use in teaching. AB - Recent developments in personal computer hardware and software allow the manipulation of radiologic images. We developed an interactive, computer-based atlas of clinical neurologic positron emission tomographic studies for use as an educational resource. A personal computer and multimedia software were used to assemble the clinical case studies. For each clinical case, the user had available the clinical history, positron emission tomographic and correlative anatomic images, study interpretation, discussion, and references. The clinical cases were selected for their educational value, either as a representative example of an abnormality or for their ability to illustrate a common pitfall in positron emission tomographic imaging of the brain. PMID- 8498237 TI - An inexpensive computer-based digital imaging teaching file. AB - Despite a decade and a half of digital imaging in radiology, most radiology teaching files remain film-based. The reasons include the high cost or unavailability of digital acquisition and display devices. In the past few years, a number of excellent exhibits that combine inexpensive microcomputers with radiologic education have been shown at national meetings [1-6]. Unfortunately, many of these methods require esoteric hardware, expensive or proprietary software, or special programming skills. We developed a simple method for creating and disseminating a teaching file of imaging studies obtained with digital techniques. PMID- 8498239 TI - Medical malapropisms. PMID- 8498238 TI - Producing picture-perfect posters. AB - Scientific posters form an integral part of many radiology meetings. They provide the opportunity for interested parties to read the material at an individualized pace, to study the images in detail, and to return to the exhibit numerous times. Although the content of the poster is undoubtedly its most important component, the visual presentation of the material can enhance or detract from the clarity of the message. With the wide availability of sophisticated computer programs for desktop publishing (DTP), one can now create the poster on a computer monitor with full control of the form as well as the content. This process will result in a professional-appearing poster, yet still allow the author the opportunity to make innumerable revisions, as the poster is visualized in detail on the computer monitor before printing. Furthermore, this process is less expensive than the traditional method of typesetting individual sections separately and mounting them on cardboard for display. The purpose of this article is to present our approach to poster production using commercially available DTP computer programs. PMID- 8498240 TI - Teleconferencing for cost-effective sharing of radiology educational resources: potential and technical development. AB - To develop a cost-effective method of sharing educational resources, a dial-up teleconferencing network was implemented between three radiologic sites for a 30 day period of evaluation. By means of standard dial-up telephone channels, compressed video and audio signals displayed radiologic images, slides, and text, allowing residents and faculty from the three sites to participate in sight and sound interactions. Each of the three sites used compressed video/audio coder decoders (codecs) conforming to the Consultative Committee on International Telegraphy and Telephony H.261 standard. Four video cameras were used at each site, and the audio was run in full duplex mode. A multipoint video bridge was used to broadcast codec output signals to the input lines of the other codecs. Our evaluation found audio quality to be suboptimal, but capable of being improved; diagnostic image quality was adequate when a video zoom mode was used; the digital-archive mode of the codec proved advantageous; the H.261 codec permitted participation from all sites; and all conference lecturers were able to conduct their conferences as they were accustomed. Although audio quality and spatial resolution need to be improved, the results of this pilot study imply that dial-up compressed video conferencing has the potential to become a practical, cost-effective method of sharing educational resources by means of interactive radiologic multisite educational programs. PMID- 8498241 TI - Cardiovascular case of the day. Abdominal coarctation due to neurofibromatosis. PMID- 8498242 TI - Cardiovascular case of the day. Aneurysm of aberrant right subclavian artery arising from diverticulum of Kommerell. PMID- 8498243 TI - Cardiovascular case of the day. Anastomotic false aneurysm of a right posterior tibial to lateral tarsal bypass graft. PMID- 8498244 TI - Chest case of the day. Mediastinal abscess. PMID- 8498245 TI - Chest case of the day. Obstructive mucoid impaction due to endobronchial tumor. PMID- 8498246 TI - Chest case of the day. Mycobacterium avium complex pulmonary disease. PMID- 8498247 TI - Abdominal case of the day. Neutropenic enterocolitis associated with acute leukemia. PMID- 8498248 TI - Abdominal case of the day. Inflammatory pseudotumor of the pancreas. PMID- 8498249 TI - Musculoskeletal case of the day. Soft-tissue implant of giant cell tumor. PMID- 8498250 TI - Musculoskeletal case of the day. Aneurysmal bone cyst. PMID- 8498251 TI - Musculoskeletal case of the day. Myelofibrosis. PMID- 8498252 TI - Pediatric case of the day. Pulmonary venoocclusive disease. PMID- 8498253 TI - Pediatric case of the day. Hemangioendothelial sarcoma. PMID- 8498254 TI - Pediatric case of the day. Testicular choriocarcinoma. PMID- 8498255 TI - Neuroradiology case of the day. Lumbar synovial cyst. PMID- 8498256 TI - Neuroradiology case of the day. Carotid arterial dissection. PMID- 8498257 TI - Neuroradiology case of the day. Pineal cyst with cerebral aqueduct obstruction. PMID- 8498258 TI - Operating at the diagnostic margins: image quality considerations. AB - Radiology, as the field of expert image interpretation, has always been faced with questions about the trade-offs between the diagnostic quality of images and other issues related to the care of patients. Historically, image quality has been sacrificed somewhat to reduce the cost of imaging procedures or to reduce radiation exposure of patients, for example. More recently, in order to improve access to imaging information, radiology departments have begun to replace traditional film-based methods with digital techniques, which in some cases have reduced image quality. This again raises the question of how much diagnostic quality can be sacrificed to achieve a competing benefit for the patient (i.e., improved access to the image data). PMID- 8498259 TI - History of the Mallinckrodt Institute of Radiology. PMID- 8498260 TI - Abstracts of scientific papers presented at the annual meeting of the Society of Uroradiology. Naples, Florida, January 1993. PMID- 8498261 TI - Glass foreign bodies. PMID- 8498262 TI - Sarcoidosis manifested as peripheral pulmonary infiltrates. PMID- 8498263 TI - Definition of terms for describing loss of gel from breast implants. PMID- 8498264 TI - Horizontal pulmonary fissure: sonographic appearance. PMID- 8498265 TI - CT findings in scimitar syndrome. PMID- 8498266 TI - Solitary rectal ulcer syndrome: transrectal sonographic findings. PMID- 8498267 TI - Ewing's sarcoma of the hand. PMID- 8498269 TI - Educational programs for deaf students. PMID- 8498268 TI - Additional references for aneurysm of a ductus arteriosus in a neonate. PMID- 8498270 TI - University and college programs for personnel in deafness. PMID- 8498271 TI - Programs for deaf-blind children and adults. PMID- 8498272 TI - Programs and services for the deaf. Supportive and rehabilitative programs. PMID- 8498273 TI - Framework for literacy: 1993 and beyond. PMID- 8498274 TI - Deafness and text-based literacy. PMID- 8498275 TI - Quantitative literacy. PMID- 8498276 TI - Reasoning skills. A key to literacy for deaf learners. PMID- 8498277 TI - The "potential" contributions of cognitive behavior modification to literacy training for deaf students. PMID- 8498278 TI - Deaf culture and literacy. PMID- 8498279 TI - Incorporating a community-oriented approach in primary care. AB - The health care system in the United States depends on primary care services. Yet the limitations imposed by traditional approaches in primary care have resulted in an unrealized potential for primary care. Currently, we rely on the motivation and initiative of persons to acquire the health care services they need, and health care providers have attempted to meet these needs. Community-oriented primary care provides an opportunity for primary care physicians to expand their range of services and their ability to reach out to people. Incorporating community-oriented primary care into primary health care has the potential to make a major contribution in reshaping health care in the United States. PMID- 8498280 TI - Simplifying health care delivery. PMID- 8498281 TI - Ritual circumcision in an infant with von Willebrand's disease. PMID- 8498282 TI - Trichloroethylene exposure. PMID- 8498283 TI - Trichloroethylene exposure. PMID- 8498284 TI - Diary from a week in practice. PMID- 8498285 TI - Nutrition and athletes. AB - Athletes differ from nonathletes in their nutritional requirements. Proper determination of nutritional needs in athletes requires knowledge of the athlete's body-fat composition and daily caloric expenditure. A balanced diet for athletes consists of 60 percent of calories from carbohydrates, 15 percent from protein and 25 percent from fat. Other important considerations include adequate intake of minerals and fluids. PMID- 8498286 TI - Hypertrophic pyloric stenosis. AB - Hypertrophic pyloric stenosis is a gastrointestinal tract disorder common in infancy. The disorder causes projectile vomiting, weight loss, and fluid and electrolyte abnormalities. The problem can usually be diagnosed by clinical symptoms and manual detection of an enlarged pylorus. When the diagnosis cannot be confirmed by these methods, however, imaging studies are relevant. Until recently, plain radiographs and upper gastrointestinal contrast studies have been used to make the diagnosis, but ultrasonography is becoming the method of choice because it is highly accurate and lacks the ionizing radiation inherent in a radiologic procedure. Surgery provides a safe and effective treatment. PMID- 8498287 TI - Depression in primary care: detection, diagnosis and treatment. Agency for Health Care Policy and Research. PMID- 8498288 TI - Vaginal infections: diagnosis and management. AB - Three common infections account for most vaginal symptoms. Successful management depends on accurate identification of the etiologic agent and appropriate treatment. Clinical examination and office laboratory tests are usually adequate to diagnose bacterial vaginosis. Diagnosis of Candida vulvovaginitis and vaginitis caused by Trichomonas may require culture. Bacterial vaginosis is usually treated with a one-week course of metronidazole; treatment during pregnancy and the benefit of concomitant treatment of sexual partners remain points of controversy. Intravaginal application of imidazoles is the recommended initial treatment of Candida vulvovaginitis, although several effective alternative treatments are available. Trichomonas vaginitis usually responds to oral metronidazole, and treatment of sexual partners is recommended. Treatment during pregnancy should be limited because of concern about teratogenic effects. Recurrent or persistent vaginal symptoms require exclusion of the possibility of reinfection or the presence of other conditions (particularly cervicitis); symptoms may respond to prolonged or prophylactic regimens. PMID- 8498289 TI - Answers to questions about the acellular pertussis vaccine. AB - Two acellular pertussis vaccines, which are usually combined with diphtheria and tetanus toxoids, are now licensed for use in the United States. These vaccines are immunogenic and produce fewer adverse reactions than whole-cell pertussis vaccines. At present, acellular vaccines are to be used only for the fourth and fifth booster doses of diphtheria-tetanus-pertussis vaccine in children 15 months of age or older. Efficacy of the acellular vaccines in younger children is currently being investigated. PMID- 8498290 TI - Shellfish-borne illnesses. PMID- 8498291 TI - U.S. Preventive Services Task Force issues scoliosis screening policy. PMID- 8498292 TI - Variability of coronary blood flow reserve assessed by Doppler catheter after successful thrombolysis in patients with acute myocardial infarction. AB - To establish whether abnormal function of small coronary vessels might limit the advantages of thrombolytic treatment, coronary flow reserve in the infarct related artery was measured in nine patients with acute myocardial infarction early after successful coronary thrombolysis by using a Doppler catheter and intracoronary adenosine infusion. In each patient coronary flow reserve was calculated as the ratio between coronary blood flow velocity during the highest tolerated intracoronary dose of adenosine (0.5 mg/min in five patients and 1 mg/min in four patients) and baseline velocity. Coronary flow reserve ranged from 1 to 3 (mean 2 +/- 0.7). No correlation (r = 0.20; p = 0.58) was found between coronary flow reserve and the severity of residual coronary stenosis, which ranged between 23% and 76% (mean 47% +/- 17%). No correlation (r = 0.33; p = 0.39) was found between either coronary flow reserve and the interval between pain onset and administration of the thrombolytic treatment, which ranged between 2.2 and 6 hours (mean 4.2 +/- 1.4 hours). Thus, in patients with acute myocardial infarction, coronary flow reserve early after successful thrombolysis is strikingly variable and may be extremely low despite widely patent epicardial coronary arteries. This restriction of coronary blood flow, probably caused by abnormal function of small coronary vessels, might limit the potential benefit from successful coronary thrombolysis. PMID- 8498293 TI - Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs. AB - Residual coronary stenosis is common after successful thrombolysis for acute infarction. We investigated the role of platelets and the influence of a residual critical stenosis during early reperfusion in survival of reperfused myocardium. The left anterior descending coronary artery was occluded for 90 minutes and reperfused for 6 hours in 5 groups of dogs, 3 with a residual critical stenosis (groups 1 through 3) and 2 without (groups 4 and 5). Thrombocytopenia was produced by an antiserum in groups 2, 3, and 5; group 3 was also made neutropenic by another antiserum. Platelets (groups 1 and 4) and neutrophils (groups 1, 2, 4, and 5) labeled with indium 111 were reinjected at occlusion. Collateral flow was estimated with radioactive microspheres and was statistically similar among groups. Infarct size (percentage of area at risk), revealed by triphenyltetrazolium, was more severe (49.4% +/- 4.0%; p < 0.05) with stenosis (group 1) than without stenosis (group 4: 29.5% +/- 4.6%). Platelet depletion reduced infarct size in group 2 (28.6% +/- 6.3%; p < 0.05 vs group 1) with stenosis, but not in group 5 without stenosis (24.5% +/- 6.2% vs group 4: 29.5% +/- 4.6%). Neutropenia (group 3) did not decrease infarct size in thrombocytopenic dogs. Neutrophil accumulations in reperfused myocardium were similar among groups, but platelets accumulated in greater numbers in reperfused infarcts with stenosis (group 1: 338,581 +/- 52,857/gm; p < 0.05) than without stenosis (group 4: 153,445 +/- 23,949/gm). Therefore a critical stenosis at reperfusion compromises myocardial salvage and increases infarct size by means of a platelet-mediated mechanism. PMID- 8498294 TI - Enhancement of thrombolysis by external ultrasound. AB - The purpose of our study was to assess the efficacy of external ultrasound to enhance in vitro thrombolysis with urokinase or streptokinase. One-hour-, 1-day-, 4-day-, and 6-day-old human blood thrombi (n = 366) were incubated in normal saline solution with three different concentrations of streptokinase (50, 250, and 2000 mu/ml) or urokinase (200, 2000, and 5000 mu/ml). Thrombi were exposed to pulsed ultrasound of 1 MHz at 1.0, 1.5 and 2.2 W/cm2 at different exposure times. The combination of ultrasound (2.2 W/cm2, 30 min) and urokinase or streptokinase enhanced lysis rate by an average of 25% compared with lysis with thrombolytic agents alone (p < 0.05). The enhancement was greater at higher ultrasound power outputs (2.2 W/cm2 > 1.5 W/cm2 > 1.0 W/cm2). At higher-power outputs there was no increase of temperature in the solution containing the thrombus. The extent of lysis was higher with longer ultrasound exposure time and with fresh thrombi. These data suggest that use of external ultrasound has the potential to increase both efficacy and rate of thrombolysis. PMID- 8498295 TI - Coronary stenting for treatment of acute or threatened closure following dissection after coronary balloon angioplasty. AB - We studied 32 patients (age 58 +/- 9 years) who had been treated with a Palmaz Schatz stent after significant dissection complicating percutaneous transluminal coronary angioplasty (PTCA). We attempted to cover the entire site of dissection with prosthesis. The presence of dissection after PTCA was associated with Thrombolysis in Myocardial Infarction grade 0 to 1 flow in 19 patients and grade 2 flow in 13. The stented arteries were: left anterior descending artery in 19 patients, right coronary artery in seven, and left circumflex artery in five. A single stent was implanted in 11 and multiple stents in 21 patients. Angiographic success was achieved in 30 patients (94%). Two patients (6%) had urgent coronary artery bypass graft surgery, two (6%) had a myocardial infarction, and one (3%) patient died. Subacute occlusion occurred in one patient (3%). Angiographic restenosis was found in three of nine patients (33%) with a single stent and 11 of 17 (65%) with multiple stents. Clinical follow-up at 11 +/- 3 months showed the necessity of coronary artery bypass graft surgery in two patients and repeat PTCA in nine (31%). We conclude that coronary stenting is an effective treatment for significant coronary dissection after PTCA with an acceptable incidence of major cardiac events at follow-up. PMID- 8498296 TI - Intravascular ultrasonographic assessment of the results of coronary artery stenting. AB - We studied 12 patients undergoing elective coronary stent implantation for either recurrent restenosis or adverse lesion appearance. By use of a 4.8F 20 MHz intravascular ultrasound catheter, the conventional angioplasty site was examined before and after coronary stent implantation. Quantitative angiographic analysis revealed the expected excellent final result with a group mean poststent diameter reduction of 14 +/- 9% and a cross-sectional area reduction of 22 +/- 13%. Angiographic analysis also indicated an increase in minimum stenosis diameter from 1.8 +/- 0.6 mm after conventional balloon angioplasty to 2.8 +/- 0.3 mm after coronary stent implantation. Quantitative analysis of the corresponding intravascular ultrasound images, however, revealed significant residual endoluminal obstruction. Fractional plaque area remained unchanged from 30 +/- 12% after conventional balloon angioplasty to 32 +/- 11% after stent implantation. The circumferential distribution of plaque increased significantly from 0.44 +/- 0.17 to 0.55 +/- 0.15 (p = 0.03) after stent implantation. Despite the lack of significant change in the ultrasound-determined minimum stenosis diameter after stent placement, there was a borderline significant increase in the plaque-free lumen area (before stent, 6.35 +/- 1.55 mm2; after stent, 7.25 +/ 1.6 mm2; p = 0.06). Thus, in contrast to the substantial improvement in the angiographically assessed residual luminal obstruction after stent implantation compared with the prestent condition, considerably less improvement was found by intravascular ultrasound-assessed examination. Morphometric analysis indicated a tendency toward circumferential remodeling of plaque. The inherently different approaches to vascular imaging represented by contrast angiography and intravascular ultrasound techniques appear to provide complementary information.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498297 TI - Enhanced detection of cardiac allograft arterial disease with intracoronary ultrasonographic imaging. AB - Intracoronary ultrasonographic imaging was performed in 60 patients 0.3 to 9 years (mean 2.9 +/- 1.9) after heart transplantation. By using a 1.8 mm intravascular ultrasonographic catheter, 192 (80%) of 240 angiographically visualized major epicardial coronary arteries (right, left main, anterior descending, and circumflex) were imaged by ultrasonography. Coronary luminal irregularities were detected in 15% of arteries by angiography compared with 34% by ultrasonography (p < 0.0001). The typical abnormality detected by ultrasonography consisted of crescentic and/or concentric intimal and medial thickening. Calcification in vascular lesions was rare (< 1% of arteries studied). Although the prevalence of angiographic abnormalities tended to be time dependent, ultrasonographic abnormalities were more strongly associated with donor age (normal, 22 +/- 8 years, vs abnormal, 33 +/- 10 years; p < 0.0001). Cardiac allograft coronary arterial disease is significantly underestimated by contrast angiography. Intravascular ultrasonography may provide a useful adjunct for identification and serial follow-up of this significant problem. PMID- 8498298 TI - Percutaneous transluminal coronary angioplasty through 6F diagnostic catheters: a feasibility study. AB - This study evaluated the feasibility of performing coronary angioplasty through 6F diagnostic catheters by mainly using over-the-wire balloon systems on 84 lesions in 70 patients. Procedural variables, including vessel opacification and angioplasty outcome, were assessed. Changes in hematocrit after angioplasty were compared for 6F versus 7F and 8F systems. Successful 6F dilatation was performed in 72 (85.7%) of 84 lesions and 58 (82.9%) of 70 patients. Seven of the 12 lesions unable to be dilated with 6F systems were successfully dilated with larger French systems. Coronary artery opacification with the 6F catheters after balloon dilation was less than optimal with the balloon and guidewire still in the catheter. Changes in hematocrit after 6F procedures were significantly less than for 8F procedures (-2.1% vs -4.2%, respectively, p < 0.01) but not for 7F procedures (-2.4%, p = not significant). Potential cost savings for angioplasty with 6F diagnostic catheters could be significant. Thus angioplasty with over-the wire balloon systems in which 6F nontapered diagnostic catheters are used can be performed safely and with less procedural blood loss than with 8F systems. Significant problems encountered with the current catheter design were poor vessel opacification after balloon dilation and difficulties with balloon retraction. PMID- 8498299 TI - Autonomic correlates of late infarct artery patency after first myocardial infarction. AB - Occlusion of the infarct-related artery has recently been associated with an increased risk of sudden death, particularly in patients with poor left ventricular function. Depressed heart rate variability (HRV) also identifies postinfarction patients at an increased risk of sudden death. The correlation between infarct artery patency, left ventricular function, and HRV was therefore examined in 186 survivors of a first myocardial infarction. Predischarge coronary angiography and Holter monitoring were carried out in 186 patients with a first acute myocardial infarction. Coronary angiography was performed because of abnormal predischarge exercise test findings. Mean age (56 +/- 9 years) and the proportions of type and site of infarction did not differ between patients with occluded or patent arteries or between patients who did or did not undergo coronary angiography. The mean left ventricular ejection fraction (EF) was 55 +/- 15% in patients with patent and 49 +/- 14% in those with occluded infarct arteries (p < 0.001), and the EF was < 40% in 17% and 28% of the respective groups (p < 0.05). HRV was < 20 U in 7 (18%) of the 39 patients with an EF < 40% but in only 7 (5%) of the 147 patients with an EF > 40% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498300 TI - Relation of fibrinogen to presence and severity of coronary artery disease is independent of other coexisting heart disease. The ECAT Angina Pectoris Study Group. AB - Six hundred fifty seven patients with angina pectoris underwent coronary angiography after measurement of plasma fibrinogen levels. Coronary artery disease (CAD) was angiographically confirmed in 75% of the patients. Other cardiac disease, either alone or in combination with CAD, was diagnosed in 8% and 11% of cases, respectively; 17% of the patients had no evidence of overt heart disease. Fibrinogen concentrations showed a graded increase according to the severity of coronary stenosis (p = 0.02) but were not significantly associated with any other cardiac heart disease. However, patients with valvular heart diseases had on average a 5.9% elevation of fibrinogen levels as compared to patients without proven cardiac disease (p = 0.08), similar to the observed 6.9% increase for CAD (p = 0.005). On average, patients with cardiomyopathies or pulmonary hypertension had only a 1.6% or 1.2% increase, respectively. The increase in fibrinogen levels associated with CAD was similar in patients with and without coexisting heart diseases. The results demonstrate a significant positive relation of fibrinogen to the presence and severity of CAD irrespective of a possible confounding influence from other cardiac diseases. The results therefore lend support to the hypothesis of a pathogenetic role for fibrinogen as a cardiovascular risk factor. PMID- 8498301 TI - Correlation of adenosine echocardiography and thallium scintigraphy. AB - Echocardiography and thallium-201 imaging with coronary vasodilators such as dipyridamole have been shown to be useful in detecting the presence and prognostic significance of coronary artery disease. Adenosine, a potent and direct coronary vasodilator, has a shorter physiologic half-life than dipyridamole, which exerts its effect by blocking the cellular uptake of adenosine. Because of the potential advantage of dipyridamole, we undertook this study to determine the correlation of adenosine echocardiography with thallium scintigraphy. Forty-two patients (18 men and 24 women; mean age 64) who were unable to undergo treadmill exercise and were known or suspected to have coronary artery disease were studied. A baseline echocardiogram was obtained in four standard views followed by adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Thallium-201 was administered 3 minutes into the infusion while a second echocardiogram was performed. Thallium-201 imaging was begun immediately after the infusion of adenosine and repeated 4 hours later. Sixteen patients underwent coronary angiography within 1 month of the adenosine echocardiogram and thallium-201 study. At the peak infused dose of adenosine there was a significant increase in heart rate (12 beats/min; p = 0.0001) and rate-pressure product (1.3 x 10(3) beats/min x mm Hg; p = 0.02) and statistically insignificant decreases in systolic and diastolic blood pressures. Sixty-two percent of patients experienced side effects during the adenosine infusion, with chest pain, shortness of breath, and flushing occurring most frequently. These side effects resolved within 1 to 2 minutes after the infusion was stopped. Ischemic electrocardiographic changes occurred in 19% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498302 TI - Regional sympathetic innervation of the heart by means of metaiodobenzylguanidine imaging in silent ischemia. AB - Metaiodobenzylguanidine was used to determine regional cardiac sympathetic innervation and whether it is reduced in silent ischemia. Patients with silent ischemia (group 1, n = 6) and angina (group 2, n = 5) and normal subjects (n = 6) underwent single-photon emission tomography at 4 hours. From base to midventricle, uptake increased in group 1 (p < 0.006), group 2 (p < 0.01), and the normal subjects (p < 0.004). In group 1 anterior ventricular uptake was greater than inferior uptake at the midventricle (p < 0.03) and apex (p < 0.05). In group 2 the same relationship was demonstrated at midventricle (p < 0.01) and apex (p < 0.05). Group 2 uptake was only significantly greater than group 1 at midventricle (p < 0.05). Innervation is greatest in midventricle and the apex of the left ventricle and greater in the anterior wall compared with the inferior wall. There is no evidence of reduced innervation in silent ischemia. PMID- 8498303 TI - Complete atrioventricular block complicating inferior acute wall myocardial infarction: short- and long-term prognosis. AB - The incidence of complete atrioventricular block (AVB) in a large group of patients with Q-wave inferior acute myocardial infarction (AMI) was 251 (11%) of 2273 patients. This incidence was significantly higher in women (14%) and patients > 70 years old (15%) than in men and patients < 70 years old (10% and 9%, respectively). Patients with complete AVB exhibited more serious arrhythmic and mechanical complications during hospitalization and included more patients with very high enzyme levels than their counterparts without AVB. The in-hospital mortality rate was 92 (37%) of 251 patients with complete AVB versus 200 (11%) of 1890 in those without AVB (p < 0.0001). After adjustment for age, gender, and important anamnestic, medical, and enzymatic findings, complete AVB emerged as an independent predictor of in-hospital mortality, yielding an odds ratio of 2.0 (90% confidence interval 1.12 to 3.57). The long-term (5-year) mortality rate in hospital survivors was slightly but not significantly higher in patients with complete AVB (28%) during hospitalization than in their counterparts with no AVB (23%). In view of these data, patients with inferior AMI in whom complete AVB develops are at increased risk and may benefit from urgent revascularization; the postdischarge management of survivors with complete AVB should be no different from that of patients without AVB. PMID- 8498304 TI - Electrophysiologic testing in patients who respond acutely to intravenous amiodarone for incessant ventricular tachyarrhythmias. AB - The outcome of patients who receive intravenous amiodarone for suppression of incessant ventricular tachyarrhythmia has not been studied conclusively. We conducted a prospective study in which all patients who responded acutely to intravenous amiodarone and went on to receive a subsequent oral loading dose were subjected to electrophysiologic testing before hospital discharge to determine whether additional or alternative therapy would be required. Among 18 patients (17 with ischemic heart disease) who entered the protocol, 16 had a clinical response to intravenous amiodarone alone (12 patients) or in combination with another antiarrhythmic drug (4 patients) and survived to study. Of these, 10 had monomorphic ventricular tachycardia (VT) when first seen, five had polymorphous VT or ventricular fibrillation (VF), and three had both. In seven patients sustained monomorphic VT was inducible (group 1), and in nine it was not (group 2). The only clinical factor that distinguished group 1 from group 2 was age (group 1 > group 2). Five patients in group 1 and one in group 2 received an implantable cardioverter defibrillator; one patient in group 1 had a successful endocardial resection. During a mean follow-up period of 11 months, four patients in group 1 have had appropriate implantable cardioverter defibrillator discharges, whereas only one patient in group 2 has had a clinical event (sudden death). We conclude that intravenous amiodarone is a highly effective drug used alone or in combination to suppress spontaneous incessant VT/VF. Predischarge electrophysiologic testing, even in patients who have polymorphous VT, has predictive value over and above the observed clinical response. These preliminary results favor predischarge testing and aggressive device treatment in this cohort. PMID- 8498305 TI - Histologic study of chronic catheter cryoablation of atrioventricular conduction in swine. AB - To evaluate the efficacy of catheter cryoablation, we studied histologic changes of the atrioventricular (AV) junction in eight pigs 6 weeks after cryoablation of central conducting tissue. Cryothermia at -60 degrees C was applied to the AV junction through an 8F or 11F cryocatheter with no electrode and was maintained for 3 minutes after complete AV block was obtained. Six weeks later, gross inspection revealed a distinct, oval-shaped scar 5 to 8 mm in length along or above the septal leaflet of the tricuspid valve in each animal. Microscopically, ablated sites were discrete and were replaced by dense connective tissue with no signs of chronic inflammation. Neovascularization was often seen in scar tissue, and small branches of coronary vasculature within lesions appeared patent with mild intimal proliferation. Ablated lesions involved a small area of the summit of the muscular interventricular septum in three animals, but lesions were never found in the base of the aortic wall or aortic valve. The proximal AV conduction system, either the penetrating bundle or a portion of the AV node, was ablated in all five animals with complete AV block. Three animals that did not maintain complete AV block showed scar formation in the atrial septum above the AV node or penetrating bundle; two of these lesions had small islands of viable atrial myocardium embedded within scar tissue. Catheter cryoablation can produce lesions as effectively as those created during open-heart surgery and is a possible procedure for treatment of intractable supraventricular tachycardia. Improvements in technique or in the cryocatheter may be needed to create more reliably located and homogeneous scar. PMID- 8498306 TI - Atrial natriuretic factor release during rapid ventricular pacing: interplay between autonomic and hemodynamic stimulants. AB - Plasma levels of atrial natriuretic factor (ANF) and norepinephrine are markedly elevated during episodes of ventricular tachycardia. Although atrial distention appears to be the major stimulus for ANF release, reflex changes in autonomic tone might also contribute. Plasma ANF and norepinephrine levels, sinus node cycle length, systolic blood pressure, and mean right atrial pressure were therefore assessed during rapid right ventricular pacing at 150 beats/min for 10 minutes. In five patients (group 1) observations were made without autonomic blockade, and another five patients (group 2) had ventricular pacing after cardiac autonomic blockade. In group 1 systolic blood pressure fell during ventricular pacing from 122 +/- 4 to 105 +/- 5 mm Hg (p < 0.02), norepinephrine levels increased from 195 +/- 26 to 411 +/- 71 pg/ml (p < 0.02), and sinus node cycle length decreased from 936 +/- 99 to 688 +/- 58 msec (p < 0.02). Right atrial pressure was elevated from 2.6 +/- 0.6 to 7.4 +/- 0.6 mm Hg (p < 0.02), and ANF levels increased from 161 +/- 23 to 240 +/- 26 pg/ml (p < 0.05). Whereas systolic blood pressure, norepinephrine, sinus cycle length, and right atrial pressure returned promptly to baseline levels when ventricular pacing was stopped, ANF levels continued to rise (296 +/- 37 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498307 TI - Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure. AB - Intravenous magnesium is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum magnesium concentrations are associated with frequent arrhythmias and high mortality. This suggests that magnesium administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous magnesium infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum magnesium < or = 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in magnesium concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 +/- 207 hr 1 in patients in whom serum magnesium concentration increased > or = 0.75 mg/dl, but increased by 72 +/- 393 hr-1 in patients with a change < 0.75 mg/dl (p < 0.05). For all patients, the frequency of premature ventricular depolarizations was 283 +/- 340 hr-1 pretreatment and 220 +/- 269 hr-1 following magnesium infusion (p = 0.21). Patients with > or = 300 premature ventricular depolarizations hr-1 demonstrated a decrease from 794 +/- 309 to 369 +/- 223 hr-1 (p < 0.001). Intravenous magnesium administration decreased the frequency of couplets from 233 +/- 505 to 84 +/- 140 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498308 TI - Left ventricular-arterial coupling relations in the normal human heart. AB - This investigation was undertaken to assess left ventricular-arterial coupling relations in the normal human heart under varying loading conditions and inotropic states and thereby to establish whether the working point of the normal human heart is at optimal output or mechanical efficiency under basal hemodynamic conditions. In 22 patients with an atypical chest pain syndrome who had normal coronary arteriograms, left ventricular (LV) pressures, volumes, ejection fractions, and masses at cardiac catheterization, we acquired radionuclide angiograms in duplicate simultaneously with micromanometer LV pressures. These values were derived under control conditions and during methoxamine and nitroprusside infusions with heart rate held constant by right atrial pacing. Seven other patients underwent the same protocol but, in addition, we acquired these parameters during a steady-state, intravenous infusion of dobutamine (5 micrograms/kg/min). The interaction of LV chamber elastance (Ees) and effective arterial elastance (Ea) revealed that the normal human heart was operating at an Ees/Ea ratio of 1.62, a stroke work of 76 +/- 31 gm-m, and a mechanical efficiency (stroke work to pressure-volume area ratio [SW/PVA]) of 0.65 +/- 0.10. With an increase in LV load, the Ees/Ea ratio approached 1 (p < 0.01), LV stroke work increased (p < 0.01), and mechanical efficiency declined (p < 0.01). In contrast, during vasodilation, the Ees/Ea ratio increased to slightly above 2.0 (p < 0.01), LV stroke work decreased (p < 0.001), and mechanical efficiency improved (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498309 TI - Densitometric assessment of regional left ventricular systolic function during graded ischemia in the dog by use of dual-energy digital subtraction ventriculography. AB - Densitometric analysis of images obtained by digital subtraction angiography (DSA) allows for more reproducible and less operator-dependent quantitation of ventricular function. Conventional DSA uses temporal subtraction but is limited by misregistration artifacts. Dual-energy digital subtraction angiography (DE DSA) is immune to such misregistration artifacts. The ability of DE-DSA to quantitate changes in regional ventricular volume resulting from ischemia was tested. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images was used to quantitate regional left ventricular systolic function during four levels of ischemia ranging from mild to severe in open-chest dogs (n = 10). DE-DSA left ventriculograms were obtained by means of central venous injections of iodinated contrast medium. Ischemia was graded according to percentage of systolic wall thickening as measured by sonomicrometry. Phase-matched end systolic images were obtained at each of four levels of ischemia by subtracting an end-systolic control image from each end-systolic ischemic image. Ejection fraction images were obtained at the control level and at each level of ischemia by subtracting an end-systolic image from an end-diastolic image of the same cardiac cycle. The resulting wall motion difference signals represent the changes in regional ventricular volumes and were quantitated by densitometry. Densitometry was able to detect the effect of all levels of ischemia on regional function, even the mildest. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images provides a sensitive technique for detecting and quantitating the changes in regional left ventricular systolic volume that occur with ischemia. PMID- 8498310 TI - The role of transesophageal echocardiography in cardiac donor screening. AB - Transthoracic echocardiography has played a useful role in the screening of cardiac transplant donors. However, transthoracic echocardiograms may be suboptimal in many patients on ventilators. The role of transesophageal echocardiography in cardiac donor screening is unknown. Therefore we compared the potential benefit of transesophageal echocardiography combined with transthoracic echocardiography in 24 (16 men and 8 women) consecutive brain-dead patients with a mean age of 29 +/- 9 years (range 16 to 44 years), who were being considered as cardiac transplant donors. Transthoracic echocardiography was performed immediately before or after transesophageal echocardiography. Transthoracic echocardiography was technically difficult in 7 of 24 (29%) patients. Results of transesophageal echocardiography were abnormal in five of the seven patients and demonstrated left (n = 4) and right (n = 3) ventricular wall motion abnormalities and concentric left ventricular hypertrophy (n = 2). The four patients with wall motion abnormalities were eliminated as potential donors. In 16 of 17 patients with technically adequate transthoracic echocardiograms, transesophageal and transthoracic echocardiographic findings agreed and demonstrated normal hearts in 13 patients, left (n = 2) and right (n = 1) ventricular wall motion abnormalities in two patients, and isolated concentric left ventricular hypertrophy in one patient. In 1 of the 17 patients with a technically adequate transthoracic echocardiographic study, a bicuspid aortic valve was demonstrated by transesophageal echocardiography but not diagnosed by transthoracic echocardiography. Overall seven patients were eliminated as cardiac donors on the basis of transesophageal echocardiograms (n = 7), transthoracic echocardiograms (n = 2), or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498311 TI - Characteristics of structural heart defects in trisomy 9 and their relationship to those in trisomy 13, 18, and 21. AB - The hearts from two live-born full-term infants with nonmosaic trisomy 9 (one complete trisomy 9, one partial trisomy 9) were studied after death. Both demonstrated conal and valvular anomalies associated with ventricular septal defects. These specific malformations are discussed in relation to published cases of trisomy 9 and the cardiac defects of other autosomal trisomies (13, 18, and 21). PMID- 8498312 TI - Acute dose-response effects of intravenous disopyramide in hypertrophic obstructive cardiomyopathy. AB - To evaluate the acute hemodynamic effects of intravenous disopyramide in hypertrophic obstructive cardiomyopathy (HOCM), 25 patients (12 men, 13 women) with an average age of 40 years (range 18 to 70 years) were evaluated while undergoing cardiac catheterization-angiography. Biplane left ventricular angiography was performed with standard intracardiac-systemic hemodynamics, including resting and provoked (after ventricular premature beat) left ventricular outflow tract gradients, by using simultaneous LV and aortic pressures as disopyramide was being administered (total dose 100 mg, bolus 10 mg every 3 minutes). Average baseline thermodilution cardiac output equalled 4.5 +/- 1.2 L/min, with all 25 subjects demonstrating systolic anterior motion of the mitral apparatus (mild, 3 [12%]; moderate, 8 [32%]; severe, 14 [64%]). Although heart rate originally slowed during disopyramide administration, average heart rate increased during the final stages (before, 78 +/- 15 vs after, 82 +/- 13 beats/min; p < 0.05). Systemic aortic pressures increased during intravenous disopyramide (before, 107 +/- 21/71 +/- 19 mm Hg vs after, 120 +/- 28/81 +/- 13 mm Hg; p < 0.05), with a decline in LV end-diastolic pressure (before, 19 +/- 7 vs after, 16 +/- 6 mm Hg; p < 0.01). Maximum LV systolic pressures decreased (before, 193 +/- 32 vs after, 146 +/- 29 mm Hg; p < 0.01), with a substantial reduction in resting LV outflow tract gradients (before, 86 +/- 34 vs after, 27 +/- 20 mm Hg; p < 0.001) in conjunction with less inducible obstruction (before, 124 +/- 33 vs after, 64 +/- 33 mm Hg; p < 0.001). Only minor electrocardiographic changes were seen during disopyramide infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498313 TI - Increased prevalence of abnormal signal-averaged electrocardiograms in older patients who have hypertension with low diastolic blood pressure. AB - Greater mortality in hypertensive patients with the lowest diastolic blood pressure (DBP) values has been reported and may be partially explained by more fatal arrhythmias. The records of 135 patients were reviewed to determine whether the prevalence of an abnormal signal-averaged electrocardiogram (SAECG+), a risk marker for ventricular arrhythmias, was greater in patients who have hypertension with DBP < 85 mm Hg. SAECG+ was present in 31 (39%) of 80 patients with hypertension and 13 (24%) of 55 subjects with normotension p < 0.05. Hypertensive patients were more likely than normotensive subjects to have left ventricular hypertrophy (LVH, p = 0.01) and LV dysfunction (p < 0.01). In multivariate analysis only age and systolic dysfunction emerged as significant predictors of SAECG+. Among 68 hypertensive patients and for whom recent DBP data were available, SAECG+ was present in 18 of 37 with DBP < 85 mm Hg (group 1), 1 of 12 with DBP 85 to 94 mm Hg (group 2, p < 0.05 vs group 1), and 4 of 19 with DBP > 95 mm Hg (group 3, p < 0.05 vs group 1, p = 0.08 vs group 2). There were no significant differences between the three groups of hypertensive patients for coronary artery disease, LVH, systolic dysfunction, or left-sided cardiac chamber enlargement. Multivariate analysis in hypertensive patients indicated that age and DBP were each independently predictive of SAECG+, whereas the indexes of heart disease were not. Within group 1, those with SAECG+ were significantly older (68 +/- 1 vs 59 +/- 1 years, p < 0.01) and more likely to have LVH (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498314 TI - Double-blind evaluation of the dose-response relationship of amlodipine in essential hypertension. AB - To determine the dose-response efficacy of once-daily administration of placebo or a new long-acting calcium channel blocker amlodipine in patients with mild to moderate hypertension, a randomized, multicenter, placebo-controlled, double blind trial was conducted. The study included 210 patients with diastolic hypertension (blood pressure 95 to 114 mm Hg) without major hematologic, renal, hepatic, cardiac, or endocrine abnormalities. After a 4-week single-blind placebo run-in period, patients were given placebo or amlodipine (1.25, 2.5, 5, or 10 mg) daily for 4 weeks. To assess the antihypertensive effect of amlodipine over a 24 hour period, blood pressure and pulse rate at weeks 0 and 4 were recorded for 12 hours after the dose and then again at 24 hours. At the end of the study patients treated with all doses of amlodipine greater than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing positions. Amlodipine, 1.25 mg daily, was also associated with a decrease in standing diastolic blood pressure. Response to treatment was greater in all amlodipine-treated patients than in those receiving placebo. Pulse rate in both the supine and standing positions was not significantly affected by amlodipine. At doses of 2.5, 5.0, or 10.0 mg daily, amlodipine maintained blood pressure below values obtained with placebo throughout the 24-hour period. Treatment with amlodipine was well tolerated and the incidence of side effects was low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498315 TI - Impaired left ventricular filling in borderline hypertensive patients without cardiac structural changes. AB - To determine the effect of borderline hypertension on left ventricular diastolic performance, 16 patients with borderline hypertension who did not have left ventricular hypertrophy and 16 age-sex-matched patients with normotension of similar age and body mass index were investigated. Pulsed Doppler echocardiography was used to record left ventricular filling signals at rest and immediately after supine ergometer exercise. All subjects had normal left ventricular structure and systolic function. At rest the borderline hypertension group in comparison with the normotension group had a depressed peak velocity of early filling (E) (44 +/- 7 vs 54 +/- 10 cm/sec; p < 0.01), no enhanced peak velocity of late filling (A) (52 +/- 8 vs 50 +/- 11 cm/sec; not significant), and a reduced E/A ratio (0.9 +/- 0.2 vs 1.1 +/- 0.3; p < 0.05). Atrial filling time and preejection period were similar in the two groups. The effect of exercise on left ventricular filling velocity in patients with borderline hypertensive resembled that in those with normotension. Percentage changes in E (+14% +/- 12% vs +14% +/- 13%) and A (+13% +/- 8% vs 11% +/- 12%) were equivalent, suggesting a preserved diastolic reserve for exercise in the borderline hypertension group. In conclusion, borderline hypertension appears to be predictive of early filling impairment, and a late filling compensative mechanism is not yet apparent. These findings in borderline hypertension without apparent cardiac damage call for clinical attention to prevent further deterioration in cardiac function. PMID- 8498316 TI - Prediction of cardiovascular death by means of clinical and exercise test variables in patients selected for cardiac catheterization. AB - The objective of this report is the development of a population-specific prediction rule based on clinical and exercise test data that would estimate the risk of cardiovascular death in patients selected for cardiac catheterization. Prospective data and follow-up information were obtained from patients who underwent cardiac catheterization soon after clinical assessment and exercise testing. Males (n = 588) referred for evaluation of coronary heart disease from 1984 to 1990 were selected after exclusion of patients with significant valvular heart disease and patients with prior cardiac surgery. Half had a prior myocardial infarction and half complained of typical angina pectoris. All patients performed a treadmill test and were selected for clinical reasons to undergo coronary angiography within 3 months. Over a mean follow-up period of 2.5 years (+/- 1.4 years), there were 39 cardiovascular deaths and 45 nonfatal myocardial infarctions. The Cox proportional hazards model demonstrated the following characteristics to be statistically significant independent predictors of time until cardiovascular death: history of congestive heart failure (hazards ratio of 4), ST depression on the resting ECG (hazards ratio of 3), and a drop in systolic blood pressure below the resting value during exercise (hazards ratio of 5). Exercise-induced ST depression was not associated with either death or nonfatal myocardial infarction. A simple score based on one item of clinical information (history of congestive heart failure), a resting ECG finding (ST depression), and an exercise test response (exertional hypotension) stratified our patients for 4 years after testing from 75% with a low risk (annual cardiac mortality rate of 1%), 17% with a moderate risk (annual mortality rate of 7%), and 1% with a high risk (annual cardiac mortality rate of 12%, with a hazards ratio of 20 and 95% confidence interval from 6 to 70X). It was concluded that the variables available from the usual noninvasive workup of patients with known or suspected coronary artery disease enable prediction of risk of cardiovascular death. Three quarters of those usually undergoing cardiac catheterization can be identified by simple noninvasive variables as being at such low risk that invasive intervention is unlikely to improve prognosis. PMID- 8498317 TI - Coronary and circulatory support strategies for percutaneous transluminal coronary angioplasty in high-risk patients. AB - PTCA is now applied to patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease, and impaired left ventricular function. To minimize the risk during angioplasty, several coronary and systemic circulation support approaches have been developed as adjuncts to high-risk angioplasty. Local coronary support techniques include the perfusion balloon catheter, the coronary stent, directional coronary atherectomy, laser balloon angioplasty, perfluorocarbon coronary perfusion, coronary sinus retroperfusion, and distal coronary hemoperfusion. Systemic circulatory support includes intraaortic balloon counterpulsation, cardiopulmonary support, the hemopump, and left heart partial bypass. These support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization. PMID- 8498318 TI - Deep hypothermic circulatory arrest during cardiac surgery: effects on cerebral blood flow and cerebral oxygenation in children. AB - Deep hypothermic circulatory arrest has become an essential technique to allow repair of complex congenital cardiac lesions in children. The arrested state has concerned the surgeon, cardiologist, and anesthesiologist alike, and yet deep hypothermic circulatory arrest has been highly successful with a low incidence of neurologic sequelae. Studies of cerebral blood flow and cerebral oxygenation demonstrate that the arrest hypothermic brain does not develop the immediate postarrest hyperemia or hyperoxia seen in normothermic ischemic brain models. However, both hypothermic and normothermic ischemic brains exhibit hypoperfusion beyond the immediate recirculation period, likely coupled with a reduced cerebral metabolic rate. That the hypothermic arrested brain likely becomes anoxic and recovery of the anoxic brain depends in large part on recirculatory hemodynamics suggests that the lack of hyperemia and hyperoxia may play more major roles than was previously believed. The mechanism of protection may be related to suppression of oxygen free radicals. PMID- 8498319 TI - Directional atherectomy: combining basic research and intervention. PMID- 8498320 TI - Oversize balloon atrial septal dilatation: early experience. PMID- 8498321 TI - Graded balloon dilation atrial septostomy as a bridge to lung transplantation in pulmonary hypertension. PMID- 8498322 TI - Fixed-wire balloon dilation of critical pulmonary stenosis. PMID- 8498323 TI - Angina pectoris due to left main coronary artery compression in Eisenmenger ductus arteriosus. PMID- 8498324 TI - Occlusive thrombosis in myocardial bridging. PMID- 8498325 TI - Critical left main stenosis presenting as diffuse ST segment depression. PMID- 8498326 TI - Transmural rupture of a nondissecting aortic aneurysm diagnosed by transesophageal echocardiography. PMID- 8498327 TI - Brucella mycotic aneurysm of ascending aorta complicating discrete subaortic stenosis. PMID- 8498328 TI - Transvenous biopsy of intracardiac tumor under transesophageal echocardiographic guidance. PMID- 8498329 TI - Dual antegrade His bundle pathways with alternating bundle branch block. PMID- 8498330 TI - Cardiogenic seizure with bradyarrhythmia: documentation of the mechanism during asystole. PMID- 8498331 TI - Apical left ventricular lipoma presenting as syncope. PMID- 8498332 TI - Primary intimal sarcoma of the pulmonary trunk simulating pulmonary embolism. PMID- 8498333 TI - Left ventricular outflow tract to left atrial communication due to mitral valve endocarditis. PMID- 8498334 TI - Intracardiac thyroid heterotopia. PMID- 8498335 TI - Solitary left ventricular metastasis of renal cell carcinoma. PMID- 8498336 TI - Initial detection in a teenager of anomalous left coronary artery from the pulmonary artery by color Doppler echocardiography. PMID- 8498337 TI - Natural anticoagulants in smokers. PMID- 8498338 TI - Adenosine AV block. PMID- 8498339 TI - Left ventricle in RV dysplasia. PMID- 8498340 TI - ANF rise during PTCA. PMID- 8498341 TI - Left atrial ball thrombus. PMID- 8498342 TI - Stiff LA syndrome. PMID- 8498343 TI - Heart failure versus CHF. PMID- 8498345 TI - Single-vessel PTCA. PMID- 8498344 TI - ANF in CHF. PMID- 8498346 TI - Q fever-induced EMF. PMID- 8498347 TI - AIDS and primary pulmonary hypertension. PMID- 8498348 TI - Bepridil and agranulocytosis. PMID- 8498349 TI - ECG differentiation of muscular dystrophy types. PMID- 8498350 TI - Dr. Ing and CPR. PMID- 8498351 TI - Septal puncture for balloon mitral valvoplasty. PMID- 8498352 TI - Clinical significance of ANP. PMID- 8498353 TI - Intraoperative tee in aortic valve repair. PMID- 8498354 TI - Static balloon dilatation of the atrial septum. PMID- 8498355 TI - Rate-adaptive cardiac pacing: cost versus technology versus patient benefit. PMID- 8498356 TI - A task-based statistical model of a worker's exposure distribution: Part I- Description of the model. AB - The authors present a task-based model to describe a single worker's exposures to a single airborne chemical toxicant. The model accounts for variability in short term time-weighted average (TWA) exposure values within a task, and for variability in arithmetic mean exposure levels between tasks. For a given workday, the 8-hour TWA value is equated with the sample mean of an appropriate number of short-term TWAs arising from stratified random sampling of short-term TWAs with proportional allocation by task. The model accounts for autocorrelation in the stochastic process that generates successive short-term TWA values. Due to the underlying random process, a given type of workday with regard to the set of task times has an associated distribution of 8-hour TWA values; the variance of this distribution increases with increasing autocorrelation in the time series of short-term TWAs. A worker's total distribution of 8-hour TWAs is a mixture of these day-specific distributions weighted by the relative frequency of each type of workday; the variance of the total distribution increases with greater day-to day variability in the array of task times. PMID- 8498357 TI - A task-based statistical model of a worker's exposure distribution: Part II- Application to sampling strategy. AB - A task-based statistical model of a worker's exposure distribution for an airborne chemical toxicant is applied to estimating the long-term average exposure level, mu. The precision in estimation is represented by the variance of the sample estimator, denoted by Var[mu]. A traditional sampling strategy consists of integratively measuring the 8-hr time-weighted average exposure level on randomly selected workdays, and computing the sample mean; this strategy is termed "simple one-stage cluster sampling," where each 8-hr workday is a cluster of thirty-two 15-min periods. Three alternative strategies involving measurements of 15-min TWAs are examined: simple random sampling of 15-min periods, and stratified random sampling of 15-min periods with proportional allocation by task, and with optimum allocation by task. All four survey designs provide unbiased estimates of mu. However, for a fixed cost, the stratified sampling designs may provide a lower Var[mu] than simple one-stage cluster sampling for less work time monitored. PMID- 8498358 TI - Physiological responses of firefighting students during simulated smoke-diving in the heat. AB - While wearing a self-contained breathing apparatus and fire-protective clothing, 35 healthy firefighting students aged 19-27 years performed smoke-diving (entry into a smoke-filled room) during a simulated shipboard fire. The mean (+/- SD) ambient temperature inside the simulator was 119 +/- 12 degrees C, and the task lasted 17 +/- 4 min. All subjects were fit according to their maximal oxygen consumption, which was 52.4 +/- 5.2 mL/min/kg (4.08 +/- 0.45 l/min). During the smoke-diving the average heart rate was 150 +/- 13 beats/min (79 +/- 6% of maximal heart rate attained in a cycle-ergometer test), and the peak heart rate was 180 +/- 13 beats/min (95 +/- 6% of maximal heart rate). The estimated oxygen consumption was 2.4 +/- 0.5 L/min (60 +/- 12% of maximal oxygen consumption). Neither ability to tolerate stress (as determined by the instructors) nor previous experience in smoke-diving tasks seemed to influence the heart rate or estimated oxygen consumption during experiment. Smoke-diving was physically very demanding even for the young and fit subjects, showing the importance of regular evaluation of the health and physical fitness of every firefighter who has to carry out smoke-diving tasks. PMID- 8498359 TI - The importance of width in asbestos fiber carcinogenicity and its implications for public policy. AB - Evidence from human epidemiology, experimental animal implantation and inoculation studies, and lung burden studies show that fibers with widths greater than 1 micron are not implicated in the occurrence of lung cancer or mesothelioma. Furthermore, it is generally believed that certain fibers thinner than a few tenths of a micrometer must be abundant in a fiber population in order for them to be a causative agent for mesothelioma. These conclusions are fully consistent with the mineralogical characteristics of asbestos fibers, which, as fibrils, have widths of less than 1 micron and, as bundles, easily dissagregate into fibrils. Furthermore, the biological behavior of various habits of tremolite shows a clear dose-response relationship and provides evidence for a threshold between fiber width and tumor experience in animals. Public policy in regulating mineral fibers should incorporate this knowledge by altering the existing federal asbestos fiber definitions to reflect it. PMID- 8498360 TI - Evaluation of sampling and analytical methods for the determination of chlorodifluoromethane in air. AB - In January 1989, the Occupational Safety and Health Administration (OSHA) published revised permissible exposure limits (PELs) for 212 compounds and established PELs for 164 additional compounds. In cases where regulated compounds did not have specific sampling and analytical methods, methods were suggested by OSHA. The National Institute for Occupational Safety and Health (NIOSH) Manual of Analytical Methods (NMAM) Method 1020, which was developed for 1,1,2-trichloro 1,2,2-trifluoroethane, was suggested by OSHA for the determination of chlorodifluoromethane in workplace air. Because this method was developed for a liquid and chlorodifluoromethane is a gas, the ability of NMAM Method 1020 to adequately sample and quantitate chlorodifluoromethane was questioned and tested by researchers at NIOSH. The evaluation of NMAM Method 1020 for chlorodifluoromethane showed that the capacity of the 100/50-mg charcoal sorbent bed was limited, the standard preparation procedure was incorrect for a gas analyte, and the analyte had low solubility in carbon disulfide. NMAM Method 1018 for dichlorodifluoromethane uses two coconut-shell charcoal tubes in series, a 400/200-mg tube followed by a 100/50-mg tube, which are desorbed with methylene chloride. This method was evaluated for chlorodifluoromethane. Test atmospheres, with chlorodifluoromethane concentrations from 0.5-2 times the PEL were generated. Modifications of NMAM Method 1018 included changes in the standard preparation procedure, and the gas chromatograph was equipped with a capillary column. These revisions to NMAM 1018 resulted in a 96.5% recovery and a total precision for the method of 7.1% for chlorodifluoromethane. No significant bias in the method was found. Results indicate that the revised NMAM Method 1018 is suitable for the determination of chlorodifluoromethane in workplace air. PMID- 8498361 TI - Reducing exposures during the pouring operations of a brass foundry. AB - The focus of this exposure assessment and control technology study was a brass foundry and the lead exposures of workers involved in the transportation and pouring of metal. Controls in place at the foundry included ventilation systems at the furnace and along the continuous and stationary pouring lines. Real-time measurements were made to determine which tasks were the primary exposure sources, and a hand-held aerosol monitor was used to measure real-time aerosol exposures (as a surrogate for lead) in the workers' breathing zones. Data were collected over two 30-min sampling periods while worker activities were monitored using a video camera. Analysis of the data showed that the greatest aerosol exposures occurred during the transportation of an unventilated, full ladle, resulting in an average concentration of at least twice that of the other tasks. The study concluded that the addition of exhaust ventilation such as a moveable hood and duct system during the ladle transport and pouring tasks, and the implementation of a side draft hood at the pigging area, could result in a reduction of worker exposure to aerosols during the continuous pouring operation by up to 40%. The controls and techniques suggested in this study could be applied to pouring operations throughout the industry to reduce worker exposure to metal fumes. PMID- 8498362 TI - The difficulties with low-level asbestos exposure assessments in public, commercial, and industrial buildings. AB - A method by which the airborne concentration of asbestos, low enough to substantiate that a significant health risk does not exist, is presented. The method is different from that used for the determination of occupational exposure, which is shown to be inadequate in this concentration range and a justification of how this alternative procedure might be used to achieve compliance is put forward. The difficulties associated with both the physical measurement and the significance of the concentrations that are determined are discussed. PMID- 8498363 TI - Exercise thallium-201 scintigraphy after thrombolytic therapy with or without angioplasty for acute myocardial infarction. AB - Scant data are available concerning the application and results of exercise thallium-201 (Tl-201) scintigraphy after acute myocardial infarction (AMI) treated with thrombolytic therapy. The goals of this study were to determine the ability of exercise Tl-201 scintigraphy to detect inducible ischemia and to identify multivessel coronary artery disease (CAD) in 88 consecutive postinfarction patients who received thrombolytic therapy and underwent both predischarge noninvasive testing and coronary angiography. Exercise-induced Tl 201 redistribution on quantitative scintigraphy was significantly more prevalent than exercise ST-segment depression (48 vs 14%, p < 0.001). Sensitivity and specificity of exercise ST depression alone for identification of multivessel disease was 29 and 96%, respectively. Sensitivity of a remote Tl-201 defect for multivessel CAD detection was 35 and 87%, respectively--not significantly different from values for ST depression alone. When considered as a single variable, the presence of either ST depression or a remote Tl-201 defect was associated with a 58% sensitivity (p < 0.05, compared with either ST depression or Tl-201 redistribution alone), but a somewhat diminished specificity of 78%. There was no difference in extent or severity of angiographic CAD in patients with multivessel CAD with or without inducible ischemia. In conclusion, this study shows that exercise Tl-201 imaging is more sensitive than exercise Tl-201 imaging is more sensitive than exercise ST depression for detection of residual ischemia during submaximal exercise in patients who received thrombolytic therapy for AMI. The combination of the presence of either Tl-201 redistribution or ischemic ST depression was better than either variable alone for identifying patients with multivessel CAD. PMID- 8498364 TI - Comparison of models for quantitative left ventricular wall motion analysis from two-dimensional echocardiograms during acute myocardial infarction. AB - To develop quantitative analysis of regional left ventricular wall motion in the absence of a gold standard, an objective statistical measure to compare models of wall motion is described. This measure can be derived from wall motion analysis of subgroups of patients with different patterns of wall motion. A priori knowledge of the exact localization of wall motion abnormalities is not needed. Two-dimensional echocardiograms were analyzed from 79 patients with myocardial infarction. The following 4 models were compared: Model I was based on the descent of the base toward the stable apex during systole. Models II and III measured area reduction with fixed- and floating-reference systems, respectively. Model IV was the centerline model. Classification by the electrocardiogram of the myocardial infarction as anterior (n = 37), posterior (n = 17) and inferior (n = 25) provided the a priori probability for classification of myocardial infarction. The a posteriori probability for classification of myocardial infarction was derived from the detection of wall motion abnormalities by echocardiographic analysis. The mean difference between a posteriori and a priori probability is a measure for the diagnostic value of the model, and was measured for 200 regions/patient. Use of the described measure revealed model I to be the most informative model and model III the least informative. Thus, the described statistical measure contributes to the development of regional wall motion analysis. PMID- 8498365 TI - Prognostic significance from 10-year follow-up of a qualitatively normal planar exercise thallium test in suspected coronary artery disease. AB - A normal exercise thallium-201 scintigram has been shown to confer an excellent prognosis over a 1- to 4-year follow-up period. However, progression of coronary disease could result in cardiovascular mortality with increasing time. Therefore, the vital status of 309 patients with normal stress thallium myocardial imaging was determined after an average of 10.3 years. Deaths were classified as cardiac or noncardiac. Statistical analysis was performed using Kaplan-Meier survival curves. Standardized mortality ratios were calculated and compared with those of an age- and sex-matched general population. Follow-up was complete in 288 patients (93%). Of 18 deaths, only 3 were cardiac; the remaining 15 were mainly secondary to cancer. Thus, cardiac mortality was 1% and total mortality 6.3% at 10 years. In addition, both all-cause and cardiac mortality rates were significantly less than would be expected in an age- and sex-adjusted segment of the general population. Thus, normal exercise thallium scintigraphy retains its high negative predictive value for death < or = 10 years after initial testing. This supports the use of stress thallium imaging to predict which patients with suspected coronary artery disease are at low risk for cardiac death and thus do not need invasive testing. PMID- 8498366 TI - Treatment of long coronary artery narrowings with long angioplasty balloon catheters. AB - Balloon angioplasty of long coronary artery narrowings has been associated with a lower rate of acute success, and a higher rate of acute complications and restenosis than that observed for short narrowings. Angioplasty catheters with longer length balloons (30 and 40 mm) are now available, and the objective of this study was to determine the acute and long-term success for patients with long coronary artery narrowings treated with these longer balloons. All patients with long narrowings (> or = 10 mm) treated with long balloons at 1 institution over a 1-year period were identified (93 narrowings in 89 patients), and acute and long-term outcomes were carefully documented. Procedural success (residual stenosis < or = 50%) was 97%. Abrupt closure occurred in 6% and major dissection in 11% of narrowings. Clinical success (procedural success without in-hospital death, bypass surgery or myocardial infarction) was achieved in 90% of patients. Repeat catheterization was performed in 61 patients (76% of those eligible), and restenosis was found in 50 to 55%, depending on the definition used. The treatment of long coronary artery narrowings using angioplasty catheters with longer balloons leads to high rates of acute success. However, there is a high rate of restenosis. New interventional devices for long lesions should be compared with long balloons in a randomized controlled trial. PMID- 8498367 TI - Effects of diet and lifestyle changes on atherosclerotic risk factors after 24 weeks on the Indian Diet Heart Study. AB - In a randomized, single-blind, controlled trial, 621 patients were assigned either intervention diet A (group A, 310 patients) or control diet B (group B, 311 patients) for a period of 24 weeks. After 24 weeks as revealed by dietary questionnaires, group A patients received: (1) a diet with a higher percentage of calories from fruits and vegetables and complex carbohydrates; (2) a higher polyunsaturated/saturated fat ratio diet; and (3) a larger amount of soluble dietary fiber, antioxidant vitamins and minerals and low saturated fat and cholesterol than group B. Group A patients also did more physical and yogic exercises than group B. Adherence to diet and exercise was obtained through questionnaires and information obtained was quantified into a formula. After 24 weeks, the overall score of diet and exercises was significantly higher in group A than in group B. There was a significant decrease in serum total cholesterol (13.3%), low-density lipoprotein cholesterol (16.9%), triglycerides (19.2%), fasting blood glucose (19.5%) and blood pressures (11.5/6.2 mm Hg) in the intervention group compared with initial levels and changes in group B. The effect of exercise on the decrease in risk factors was additive. Within group A, overall score for diet and exercise was greater in 1 subset of 116 patients in the intervention group which had maximal lifestyle changes. A separate analysis of data in this subgroup revealed a greater decrease in risk factors compared with risk factor changes in the remaining 194 patients with less higher overall score; this indicated that the relation of lifestyle changes with reduction in risk factors may be of causal nature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498368 TI - Prospective evaluation of day-to-day reproducibility of upright tilt-table testing in unexplained syncope. AB - To evaluate the day-to-day reproducibility of upright tilt-table testing, 109 patients with unexplained syncope prospectively underwent testing on 2 consecutive days using a uniform protocol. Results of testing on 2 separate days were concordant in 69 of 109 patients (63%), and discordant in 40 of 109 patients (37%). Thirty-six of 109 patients (33%) had vasodepressor syncope on 1 or both days of testing. Nineteen of 30 patients (63%) with vasodepressor responses on the first day did not reproduce this response during the second day of testing. An additional 6 patients with an initial negative tilt test had a vasodepressor response on the second day. Only 11 of 36 patients (31%) had reproducible vasodepressor responses on both days of testing. Patients with reproducible vasodepressor responses had a significantly higher mean number of preceding clinical syncopal events than patients with 2 normal tests (p < 0.02) or nonreproducible results (p < 0.04). In addition, these patients had a significantly longer duration of clinical symptoms relative to patients with 2 tests that yielded negative results (p < 0.008) and nonreproducible results (p < 0.01). The elapsed time between the most recent clinical event and the performance of tilt-table testing was not significantly different among the 3 groups, and did not appear to influence the outcome of testing. These data show that vasodepressor responses elicited by upright tilt-table testing show day-to day variability in many patients, a finding that may limit the interpretation of initial and follow-up test results. PMID- 8498369 TI - Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. AB - Plasma endothelin concentrations were evaluated in 53 chronic, congestive heart failure (CHF) patients with or without history of systemic hypertension, as well as in 9 with hypertension only and in 22 healthy control subjects. Plasma renin, aldosterone and atrial natriuretic peptide, as well as clinical and hemodynamic data were determined. In patients with CHF, big endothelin-1 was, independent of hypertension history, significantly greater than in hypertensive patients with normal cardiac function and in control subjects (both p < 0.0001). Patients with severe CHF had significantly greater big endothelin-1 values than did those with moderate CHF. During 12-month follow-up, 11 patients with CHF underwent heart transplantation, and 9 died; these patients had significantly greater big endothelin-1 concentrations than did the 33 clinically stable patients (p < 0.001). Big endothelin-1 and atrial natriuretic peptide correlated with right atrial pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction, effort capacity and severity of CHF (New York Heart Association functional class). PMID- 8498370 TI - Comparison of results of percutaneous balloon valvuloplasty in patients with mild and moderate mitral stenosis to those with severe mitral stenosis. The North American Inoue Balloon Investigators. AB - Most reported studies of percutaneous balloon valvuloplasty in adults with acquired mitral stenosis have used patients with severely stenosed valves. The risks and benefits of valvuloplasty were examined in a multicenter registry of patients to determine whether balloon valvuloplasty can effectively dilate less severely obstructed valves, and to clarify the role of this procedure in symptomatic patients with mild and moderate mitral stenosis. The study groups were derived from the North American Inoue Balloon Valvuloplasty Registry. Full hemodynamic data were available in 264 patients; 45 (17%) with mild or moderate mitral stenosis (mitral valve area > or = 1.3 cm2) were compared with the remaining 219 with severe mitral stenosis (valve area < 1.3 cm2). Percutaneous balloon valvuloplasty was performed using the anterograde transseptal technique with an Inoue balloon. The mean age of patients with mild and moderate mitral stenosis was 53 +/- 13 years, and all were symptomatic with a mean New York Heart Association functional class of 2.9 +/- 0.7. Balloon valvuloplasty resulted in an increase in calculated mitral valve area from 1.4 +/- 0.1 to 2.3 +/- 0.7 cm2 (p < 0.05), and a final valve area > or = 1.9 cm2 was achieved in 37 patients (82%). There were no procedural deaths, but complications included right atrial perforation, transient ischemic attack and emergency surgery for severe mitral regurgitation. One-year follow-up evaluation revealed symptomatic improvement in most patients (mean New York Heart Association class 1.4 +/- 0.6; p < 0.0001). However, 2 patients needed repeat valvuloplasty for restenosis, and 5 had mitral valve replacements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498371 TI - Early and late results of percutaneous mitral valvuloplasty for mitral stenosis associated with mild mitral regurgitation. AB - To assess the influence of mild mitral regurgitation (MR) on the initial and long term results of percutaneous mitral valvuloplasty (PMV), the baseline characteristics, early results and follow-up of 102 consecutive patients with mild MR before PMV (group I) were prospectively analyzed and compared with those of 186 consecutive patients without MR (group II). Age, gender and symptomatic status were similar in both groups, but more patients in group I were in atrial fibrillation (70 vs 54%, p < 0.05) and had had a previous episode of pulmonary edema (25 vs 14%, p < 0.05). On echocardiography, patients in group I had larger left atria (58 +/- 12 vs 53 +/- 10 mm, p < 0.05) and more calcified mitral valves (score 1.9 +/- 0.8 vs 1.5 +/- 0.7, p < 0.05), but the total echocardiographic score (8.0 +/- 2 vs 7.3 +/- 2) was similar in both groups. Baseline hemodynamic data were also similar in both groups. On multivariate analysis, group I patients were only independently associated with more calcified mitral valves and larger left atria. PMV success (area gain > or = 50% without complications) was similar (88 vs 86%) in both groups, but mitral valve area gain was smaller (0.8 +/- 0.3 vs 1.0 +/- 0.3 cm2, p < 0.05) in group I. After PMV an increase in the severity of MR > or = 2 grades (17 vs 6%, p < 0.05) occurred more frequently in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498372 TI - Balloon mitral commissurotomy for mitral restenosis after surgical commissurotomy. AB - Balloon mitral commissurotomy (BMC) was performed in 113 patients. Of these patients, 27 (24%) (25 women and 2 men, aged 49 +/- 13 years) had recurrent mitral stenosis 13 +/- 6 years (range 5 to 29) after surgical commissurotomy. Eleven patients (41%) were considered at high risk for surgery. BMC resulted in an increase in mitral valve area from 1.1 +/- 0.3 to 1.9 +/- 0.7 cm2 (p < 0.0001), and a decrease in mean mitral gradient from 16 +/- 7 to 6 +/- 3 mm Hg (p < 0.0001). An optimal result of BMC (increase in valve area > or = 25% with a post-BMC valve area > or = 1.5 cm2) was obtained in 18 patients (67%). The results did not differ from those observed in the 86 patients of our entire series without prior surgical commissurotomy. Patients with an optimal result of BMC had a more recent surgical commissurotomy and lesser morphologic alterations of the mitral valve than did those with a nonoptimal result. Patients with echocardiographic scores < 10 had an 80% success rate of BMC; however, this rate decreased to 29% for those with scores > or = 10. One patient (4%) died from a cerebrovascular accident. Clinical follow-up at 1 year showed persistent clinical improvement in 89% of patients with an optimal result of BMC; 72% were in New York Heart Association class I and 17% in class II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498373 TI - Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy. AB - To assess autonomic nervous activity in patients with cardiomyopathies, analysis of heart rate variability was performed using 24-hour ambulatory electrocardiograms in 14 patients with idiopathic dilated cardiomyopathy (IDC), 15 with hypertrophic cardiomyopathy (HC) and 18 healthy subjects. Heart rate variability during the night and daytime was calculated using fast-Fourier transform, and power spectra were quantified in 2 frequency bandwidths: 0.00 to 0.15 Hz (low-frequency power [LF]) and 0.15 to 0.50 Hz (high-frequency power [HF]). Log(HF) was used as an index of parasympathetic nervous activity, and log(LF/HF), of sympathetic nervous activity. Log(HF) was significantly lower and log(LF/HF) was significantly higher in IDC. These changes were related to ejection fraction. In HC, lower log(HF) and higher log(LF/HF) were recognized only during the night, and these changes were independent of the degree of myocardial hypertrophy. Our results indicated attenuation of parasympathetic activity and enhanced sympathetic activity in HC during the night, and also in IDC. Assessment of autonomic imbalance by analysis of heart rate variability may be useful for understanding the pathophysiology of cardiomyopathies. PMID- 8498374 TI - Usefulness of transesophageal echocardiography in the pediatric catheterization laboratory. AB - Transesophageal echocardiography was performed in 51 children (aged 2 to 14 years, mean 4; weight 9 to 50 kg, mean 21) undergoing elective diagnostic or therapeutic cardiac catheterization. The interventional procedures were percutaneous balloon dilation of pulmonary (n = 8) and aortic (n = 2) valve stenosis, percutaneous closure of patent ductus arteriosus (n = 8), and attempted occlusion of Pott's anastomosis by the double umbrella device (n = 1). The diagnostic catheterizations were performed on preoperative children of whom 5 had undergone previous palliative procedures. Precise placement of the balloon across the valve, timing of balloon inflation and deflation according to real-time monitoring of ventricular function and immediate evaluation of results and complications were accomplished with transesophageal monitoring. The exact position of distal and proximal umbrellas of patent ductus occlusive devices was checked on transesophageal imaging and completeness of occlusion controlled on color Doppler. The only relevant information in the preoperative cases was the detection of a septic thrombus in a severely ill patient. With more experience and smaller probes, transesophageal echocardiography may become a new method of monitoring cardiac catheterization also in smaller children where it may reduce duration of the procedure and amount of contrast material. PMID- 8498375 TI - "Infantile" form of the scimitar syndrome with pulmonary hypertension. AB - Twenty-five newborns and infants aged < 1 year with the scimitar syndrome and pulmonary hypertension from 12 European pediatric centers were examined. Cardiac failure and severe respiratory insufficiency were always present. In 23 cases, pulmonary hypertension was due to a large shunt between abnormal arteries originating from the abdominal aorta and supplying the lower part of the right lung (vascular sequestration). In the last 2 cases, pulmonary hypertension was secondary to stenosis of the common trunk of the right pulmonary veins. Three of 10 patients who received only medical treatment survived; 2 are doing well, with pulmonary arterial pressures that have returned to normal, and the other had severe residual pulmonary hypertension. Six of 15 patients who underwent surgery survived. There were 5 ligations of a patent ductus arteriosus with 5 deaths, 3 pulmonary resections with 2 deaths, 1 dilation of a tight stenosis of the common trunk of the right pulmonary veins with 1 death, and 6 ligations of the abnormal arterial vessels with 5 surviving patients who are in good condition. Ligation of the abnormal arterial vessels appears to be the best type of treatment. PMID- 8498376 TI - Management evolution of pulmonary atresia and intact ventricular septum. AB - To examine the impact on survival and clinical course of incorporating the morphologic classification of the right ventricle into the evolving management strategy for babies with pulmonary atresia and intact ventricular septum, the surgical results and follow-up status of the first 62 consecutive patients managed in this hospital between 1979 and 1990 were reviewed. Before 1984, all 23 babies from group I underwent primary right ventricular outflow reconstruction irrespective of right ventricular morphology and size. Since 1984, depending on the morphology and size of the right ventricle, 39 babies from group II had either closed transventricular pulmonary valvotomy (n = 31) or a shunt operation (n = 8). There were 10 hospital (43%) and 2 late deaths (total mortality 52%) in our group I patients. Three of the 11 long-term survivors had cyanosis at rest but none had any residual pressure gradient across the pulmonary outflow. Group II had 6 hospital (15%) and 4 late deaths (total mortality = 26%). Of the 29 long term survivors, 9 had a second-stage right ventricular outflow reconstruction, 8 had balloon valvuloplasty and 2 had successful Fontan operation. At the latest follow-up, 5 children from this group have cyanosis at rest, 1 has a residual gradient (55 mm Hg) across the infundibulum, and 3 have right ventricular dysfunction. The hospital and total mortality for babies in group II was significantly lower than that in group I (p < 0.01). These data suggest that tailoring the treatment to the right ventricular anatomy results in a lower overall mortality although long term postoperative hemodynamic abnormalities are observed in both groups. PMID- 8498377 TI - Doppler echocardiographic evidence of left ventricular diastolic dysfunction in ankylosing spondylitis. AB - Although cardiac involvement in the form of conduction abnormalities or aortic regurgitation occurs in 5 to 10% of patients with ankylosing spondylitis, few studies have assessed left ventricular (LV) function. This study assesses the prevalence of both systolic and diastolic LV dysfunction and other cardiac abnormalities in patients with ankylosing spondylitis who have no clinical cardiac manifestations. Fifty-nine patients (49 men and 10 women, mean age 42 +/- 10 years) underwent full clinical examination, electrocardiography, 24-hour Holter monitoring and 2-dimensional, M-mode and Doppler echocardiography. Mean disease duration was 17 +/- 9 years (range 1 to 42). Seventeen patients had evidence of noncardiac extraarticular manifestations. Precordial examination was normal in all. An age- and sex-matched control group of 44 healthy subjects was also studied. On echocardiography, abnormal LV diastolic function was detected in 12 patients (20%). Prolonged isovolumic relaxation time, prolonged deceleration time, reduced rate of descent of flow velocity in early diastole (EF slope) and reversal of the early and late peak transmitral diastolic flow velocities (E/A ratio) were noted in 9 patients. In 3 patients there was an increased E/A ratio, reduced deceleration time and increased EF slope. Mild aortic regurgitation and mitral regurgitation was seen in 1 and 3 patients, respectively. No abnormalities of left atrial size, LV systolic or diastolic dimensions or wall thicknesses were noted. There was no correlation between the presence of LV diastolic dysfunction and age, disease severity, disease duration, or the presence of extraarticular manifestations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498378 TI - ST-segment depression during sleep in obstructive sleep apnea. AB - It was hypothesized that obstructive sleep apnea may precipitate myocardial ischemia, reflected by ST-segment depression, in some patients during sleep. Overnight sleep studies and simultaneous 3-channel Holter monitoring were performed on 23 consecutive patients with obstructive sleep apnea without a history of coronary artery disease. Each patient was randomly assigned to nasal continuous positive airway pressure for the first half of the night. An episode of significant ST depression was defined as > 1 mm from baseline for > 1 minute. The total duration (minutes) of ST depression was indexed to the total sleep time (minutes per hour of sleep). Seven patients (30%) had ST depression during sleep. In all 7 patients the duration of ST depression decreased during nasal continuous positive airway pressure (30 +/- 18 vs 11 +/- 13 minutes per hour of sleep) in association with a reduction in the apnea-hypopnea index (65 +/- 35 vs 7 +/- 6/hour), arousal index (49 +/- 14 vs 6 +/- 4/hour) and the duration that oxygen saturation was < 90% (44 +/- 27 vs 12 +/- 23% total sleep time). When patients were not on nasal continuous positive airway pressure, the apnea-hypopnea and arousal indexes were higher during periods of ST depression than when ST segments were isoelectric, whereas oxygen saturation was not different. These 7 patients underwent exercise testing, which was positive for inducible myocardial ischemia in 1 patient. It is concluded that ST depression is relatively common in patients with obstructive apnea during sleep and that the duration of ST depression is significantly reduced by nasal continuous positive airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498379 TI - Safety of dobutamine stress for thallium-201 myocardial perfusion tomography in patients with asthma. AB - Many patients undergoing investigation for coronary artery disease are unable to exercise adequately due to physical or psychological reasons. Thallium-201 imaging using dipyridamole or adenosine may then be a suitable method of assessing myocardial perfusion. In patients with asthma, these drugs are contraindicated because of the risk of provoking bronchospasm. This study assesses the safety of dobutamine for thallium-201 myocardial perfusion imaging in patients with asthma who were unable to perform adequate exercise. Dobutamine was infused at rates < or = 40 micrograms/kg/min in 30 asthmatic patients for thallium-201 emission tomography. The severity of the airway reactivity ranged from mild to severe (bronchodilator treatment ranging from inhaled beta 2 agonists alone to maximal therapy including oral steroids). Coronary angiography was performed in 20 patients. Minor side effects of dobutamine were frequent, but did not limit the infusion rate. There were no episodes of bronchospasm, but tolerable dyspnea occurred in 8 patients who had reversible ischemia; this rapidly resolved with termination of the infusion. There were no serious cardiac complications, but chest pain occurred in 67% of patients. Thallium-201 images were abnormal in 10 of 11 patients with coronary artery disease (sensitivity 91%) and normal in 7 of 9 with normal coronary arteries (specificity 79%). Dobutamine thallium-201 myocardial perfusion tomography is a safe procedure in patients with asthma. PMID- 8498380 TI - Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate. AB - The dual purposes of this study with positron emission tomography were to measure the effects of dobutamine on myocardial blood flow and oxidative metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13) ammonia in quantitating flow in normal subjects. Flow was quantitated with N-13 ammonia at rest and at peak dobutamine infusion (40 micrograms/kg/min) in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at rest and peak dobutamine infusion using the clearance rate of C-11 acetate, k mono (min-1). A 2 compartment kinetic model was applied to the early phase of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure products were 7,318 +/- 1,102 and 19,937 +/- 3,964 beats/min/mm Hg, respectively, and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77 +/- 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer. Rest and dobutamine flows estimated with C-11 acetate were highly correlated with those determined with N 13 ammonia (r = 0.92). k mono increased from 0.05 +/- 0.01 to 0.18 +/- 0.02 min 1, and correlated highly with the increase in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase in cardiac demand associated with dobutamine is highly correlated with an increase in supply and oxidative metabolism. C-11 acetate is a unique tracer that can be used to image both flow and metabolism simultaneously. PMID- 8498381 TI - Effects of metoprolol on heart rate variability in survivors of acute myocardial infarction. PMID- 8498382 TI - Reciprocal changes as the presenting electrocardiographic manifestation of acute myocardial ischemia. PMID- 8498383 TI - Ratio of ST-segment and myoglobin slopes to estimate myocardial salvage during thrombolytic therapy for acute myocardial infarction. PMID- 8498384 TI - A respiratory exchange ratio equal to 1 provides a reproducible index of submaximal cardiopulmonary exercise performance. PMID- 8498385 TI - Circadian variation in the success rate of intracoronary thrombolysis for acute myocardial infarction. PMID- 8498386 TI - Exercise stress tests after cardiac transplantation. PMID- 8498387 TI - Comparison of balloon dilation and stent implantation to maintain patency of the neonatal arterial duct in lambs. PMID- 8498388 TI - The connection between health promotion and health-care costs: does it matter? PMID- 8498389 TI - Two-year results of a randomized controlled trial of a health promotion program in a retiree population: the Bank of America Study. AB - OBJECTIVE: To evaluate the effectiveness of a health promotion program in a retiree population in terms of health risk reduction and reduction in medical costs. DESIGN: Randomized controlled trial. SUBJECTS: Bank of America retirees (n = 4,712), divided into 33 retiree club regions, were randomized into 3 groups and followed for 24 months by patient report and claims experience. Group 1, the intervention group, received a low-cost ($30/year), individualized, serially reinforcing health promotion program including risk appraisal, recommendation letters, and self-management materials, delivered entirely through the mail. Group 2 received risk appraisals only, without feedback, for the first 12 months and subsequently the full intervention for the second 12 months. Group 3 was followed with claims data only. Participation rates of 57% at 1 year and 47% at 2 years were achieved. MAIN RESULTS: Overall health risk scores improved by 12% at 12 months compared with control (p < 0.001) and by 23% (from baseline) at 24 months (p < 0.001). Individual health habit changes were favorable for all parameters studied, and were highly statistically significant for most variables. Similar health risk reductions were seen in age groups of 55 to 65 years, 65 to 75 years, and over 75. Cost reduction differences were more than 20% by self report (p < 0.01) and 10% by claims experience (p = 0.02) at 12 months. For the randomized controlled period of the first 12 months, reductions averaged $164 in the intervention group contrasted with an average increase of $15 in the combined control groups. CONCLUSION: Risk reduction programs directed at retiree populations can improve health risk status and can reduce costs. PMID- 8498390 TI - Blood pressure responses after carotid surgery: relationship to postoperative baroreceptor sensitivity. AB - BACKGROUND AND PURPOSE: Among hypertensive patients after carotid surgery, a group of patients with increased baroreflex sensitivity was identified. In the other group of hypertensive patients, blood pressure and reflex sensitivity were unchanged postoperatively. We hypothesized that a partial readjustment of baroreceptor sensitivity would produce more stable blood pressure profiles. METHODS: In order to test this hypothesis, a prospective, long-term follow-up study was designed. Blood pressure was monitored in 18 hypertensive and 6 normotensive patients during 6 months using a self-measurement technique. In addition, continuous 24-hour blood pressure monitoring was performed 6 months after surgery. The mean values and the ranges (amplitudes) of systolic and diastolic blood pressure were calculated as indicators for the stability of the circulatory system. RESULTS: Hypertensive patients with unchanged postoperative baroreceptor sensitivity showed significantly more pronounced instabilities of their blood pressure profiles (amplitudes of systolic and diastolic blood pressure p < 0.05 to p < 0.001). A relationship between baroreceptor function and antihypertensive therapy could also be demonstrated, with adequate therapy being much more difficult in patients with reduced or unchanged baroreceptor sensitivity. CONCLUSIONS: In contrast to vascular surgery on the aorta or in the region of the lower limbs, carotid surgery is frequently associated with blood pressure changes, demonstrating the essential role of the baroreceptors in the carotid sinus for the regulation of postoperative blood pressure. Since it seems to be the variability of blood pressure, and not the blood pressure level alone, that is critical, close blood pressure monitoring--allowing for an assessment of blood pressure variability--appears to be of particular importance in such patients. PMID- 8498391 TI - Anthropometric and pulmonary function test profiles of outpatients with stable chronic obstructive pulmonary disease. AB - PURPOSE: To determine the prevalence of abnormalities in the nutritional status, and their correlation with pulmonary function test results, in a population of outpatients with stable chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: During 1 year of study, body weight, height, triceps skinfold, arm muscle circumference, and pulmonary function parameters were assessed in 126 patients. On the basis of body mass index (BMI = weight/height2) of less than 20, 20 to 27, and greater than 27, the patients were divided into underweight (n = 29, 23%), normal weight (n = 67, 53.2%), and overweight (n = 30, 23.8%), respectively. RESULTS: Diffusing capacity for carbon monoxide (DLCO), both as absolute and percent predicted, differed significantly among the three groups, being lowest in the underweight and highest in the overweight patients. A significant and positive correlation was present between BMI as the independent variable and DLCO, forced expiratory volume in 1 second, and its ratio to forced vital capacity. A significant and negative correlation existed between BMI and residual volume and its ratio to total lung capacity. CONCLUSION: A substantial number of stable COPD patients (46.8%) have nutritional abnormalities. BMI is a simple and accurate indicator of nutritional status in these patients. BMI correlates significantly with some tests of pulmonary function. PMID- 8498392 TI - Glucose modulation of the disposal of an acute potassium load in patients with end-stage renal disease. AB - PURPOSE: Extrarenal potassium disposal plays an important role in the tolerance of an acute potassium load and is particularly critical in patients with renal failure. Insulin is known to stimulate this disposal by enhancing potassium uptake into the cells. Since dietary potassium is generally ingested in combination with carbohydrates, the predictable stimulation of endogenous insulin release may blunt the expected increase in plasma potassium. The goal of the current study was to evaluate the effect of oral glucose on the disposition of an acute oral potassium load in hemodialysis patients and in normal controls. PATIENTS AND METHODS: Eight hemodialysis patients and eight normal control subjects were studied after an overnight fast. Each subject received an oral load of potassium chloride elixir (0.25 mmol/kg). Plasma potassium was measured at baseline and at 30-minute intervals for 3 hours. On a separate study day, the subjects underwent the identical protocol, with the addition of 50 g of oral glucose to the potassium load to stimulate endogenous insulin release. The identical two experimental protocols were repeated in each subject during concomitant beta blockade with propranolol. RESULTS: The maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (0.93 +/- 0.08 versus 0.52 +/- 0.04 mmol/L, p < 0.001). Concomitant oral glucose markedly blunted the maximal rise in potassium levels in both experimental groups (0.40 +/- 0.09 and 0.22 +/- 0.07 mmol/L, respectively, p < 0.005 versus potassium alone). With concomitant beta blockade, the maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (1.11 +/- 0.12 versus 0.72 +/- 0.09 mmol/L, p = 0.02). Concomitant oral glucose again markedly blunted the maximal increase in potassium in both experimental groups (0.72 +/- 0.09 and 0.39 +/- 0.06 mmol/L, respectively, p < 0.01 versus potassium alone). The potassium load in the absence of glucose did not produce changes in plasma insulin concentration in either experimental group. The potassium load in combination with oral glucose load produced more sustained hyperinsulinemia in the dialysis patients than in the control subjects. CONCLUSIONS: Exogenous glucose, by stimulating endogenous secretion of insulin, enhances extrarenal disposal of a potassium load. This protective effect of exogenous glucose against hyperkalemia is independent of adrenergic stimulation. The beneficial effect of exogenous glucose defends against the development of severe hyperkalemia after dietary potassium ingestion, and is critically important in hemodialysis patients, due to their negligible renal potassium excretion. PMID- 8498393 TI - Triage practice guideline for patients hospitalized with congestive heart failure: improving the effectiveness of the coronary care unit. AB - BACKGROUND: Decisions regarding the appropriate timing for transfer of patients hospitalized with congestive heart failure from the coronary care unit (CCU) to the medical ward are often not based on well-founded medical data. We investigated the potential safety and effectiveness of a practice guideline recommending early "step-down" transfer of low-risk patients with congestive heart failure. PATIENTS AND METHODS: We studied the use of a practice guideline for 384 patients hospitalized with congestive heart failure in a hypothetic experiment. The guideline stated that patients without any of the following conditions may be suitable for transfer to a nonmonitored bed 24 hours after admission: acute myocardial infarction or ischemia, complications, active or planned cardiac interventions, unstable comorbidity, worsening clinical status, or lack of response to diuretic therapy. Patients with any of the above conditions were classified as higher risk and potentially not suitable for early transfer. RESULTS: Life-threatening complications were 15.2 times more likely (95% confidence interval [CI] 2.2, 70, p = 0.001) and death 14.6 times more likely (95% CI 2.1, 68, p = 0.001) if the patient was classified as "high risk" rather than "low risk" by the guideline. The negative predictive value and sensitivity of the practice guideline for detecting patients who had life threatening complications were 99.2% and 96.4%, respectively. Thirty-one percent of patients with congestive heart failure hospitalized in either the CCU or intermediate care unit were at low risk and potentially suitable for transfer to a nonmonitored bed 24 hours after admission. Use of the guideline would have reduced intermediate care unit lengths of stay from 2.91 days to 2.22 days and CCU length of stay from 2.06 to 2.04 days had it been used to triage patients with congestive heart failure. This reduction in length of stay would have resulted in 172 more intermediate care unit bed-days available per year to accommodate additional patients. On initial review, at least one cardiologist reviewer judged that use of the guideline may have adversely affected quality of care for 4% (95% CI 1%, 7%) of patients. After a consensus among the cardiologist reviewers, it was judged that the guideline may have adversely affected care for only 0.8% of patients (95% CI, 0%, 2.3%), and that no patient (95% CI 0%, 2.3%) would have had an unexpected life-threatening complication because of the guideline. CONCLUSIONS: Use of a practice guideline has the potential to reduce the intermediate care unit lengths of stay for selected low-risk patients with congestive heart failure. PMID- 8498394 TI - Value of a simple measure of estrogen status for improving the diagnosis of coronary artery disease in women. AB - PURPOSE: To determine the potential impact of estrogen status on the pretest and postexercise test diagnostic accuracy of exercise testing. PATIENTS AND METHODS: The study comprised a total of 234 women and 326 men who underwent exercise testing followed by coronary angiography. We performed incremental logistic regression analysis of pretest (age, symptoms, smoking, diabetes, cholesterol level) with and without estrogen status (defined according to menopausal and oral estrogen status) and exercise test (two ST-segment and three non-ST-segment) variables separately for men and women. Outcomes were assessed by receiver operating characteristic (ROC) curve area analysis. RESULTS: Estrogen status was an independent pretest predictor of angiographic coronary disease. Pretest ROC curve areas: women without estrogen status = 0.79, women with estrogen status = 0.85, men = 0.78 (women with estrogen status versus other groups, p < 0.001). Postexercise test ROC curve areas: women without estrogen status = 0.83, women with estrogen status = 0.87, men = 0.88 (women without estrogen status versus other groups, p < 0.001). CONCLUSION: Consideration of estrogen status allowed for a significant improvement in the pretest clinical diagnosis of coronary disease in women. When these improvements were added to the results of exercise testing, the diagnostic accuracy of the combined clinical and exercise test data was similar for men and women. Estrogen status may be an important diagnostic clinical variable in women with suspected coronary disease. PMID- 8498395 TI - Sleep apnea in male patients with the fibromyalgia syndrome. AB - PURPOSE: Fibromyalgia is a common pain syndrome that is often associated with sleep disturbances. The most characteristic pattern noted on formal sleep study is alpha-wave intrusion on delta-wave sleep. This nonrestorative sleep pattern may be endogenous, or caused by any of a number of sleep disturbances. Our goal was to determine the frequency of sleep apnea and its relationship to a nonrestorative sleep pattern in our patients with fibromyalgia syndrome. PATIENTS AND METHODS: All new fibromyalgia patients seen in the Rheumatology Clinic at Fitzsimons Army Medical Center were screened using history and physical examination for suspicion of sleep apnea. When this condition was suspected, the patients underwent formal polysomnography to delineate any sleep disturbance. RESULTS: Four of 92 women, and 13 of 25 men with the new diagnosis of fibromyalgia syndrome underwent polysomnography. Of the women, 2.2% (2 of 92) had significant sleep apnea at formal evaluation; both were obese and had obstructive findings. In contrast, 44% (11 of 25) of the men had significant sleep apnea. CONCLUSIONS: Sleep apnea is not a significant cause of fibromyalgia symptoms in females. In male patients with fibromyalgia, sleep apnea was observed in a large percentage. Fibromyalgia may be a marker for occult sleep apnea in males. PMID- 8498396 TI - Economic impact of inappropriate blood transfusions in coronary artery bypass graft surgery. AB - PURPOSE: In addition to historically important issues of blood inventory and blood safety, the costs of blood transfusion are anticipated to have an increasingly important impact on transfusion practices. To address this, we analyzed costs of blood support given to patients undergoing coronary artery bypass graft (CABG) surgery, along with costs of blood components whose transfusions were identified to be unnecessary. PATIENTS AND METHODS: Blood components transfused as part of a previously reported national, multicenter audit of 30 adult patients each at 18 institutions undergoing primary, elective CABG surgery were reviewed. RESULTS: The range of blood purchase costs among institutions was broad, varying over two-fold. The range of red cell units transfused varied over 10-fold, and the range of total components transfused varied over 40-fold. The number of blood components transfused unnecessarily represented 27% of all blood units transfused, ranging from 7% to 43% among institutions. Inappropriate transfusions accounted for 47%, 32%, and 15% of all platelet, plasma, and red cell units transfused. The mean institutional cost for all blood components transfused per patient was $397 +/- $244. The cost per patient of components transfused inappropriately was 24% of this, or $96 +/- $89 (mean +/- SD). CONCLUSION: These costs could be reduced with practice guidelines and quality improvement programs aimed at reducing the number of inappropriate transfusions. PMID- 8498397 TI - Alcoholism: the keys to the CAGE. AB - PURPOSE: To compare the efficiency of screening for alcoholism using two different introductions to the CAGE questions. PATIENTS: Forty-three alcoholics on inpatient medical and surgical services were identified through random distribution of the Michigan Alcoholism Screening Test. METHODS: Participants were randomized to two groups receiving different introductions to the CAGE questions. Group I was introduced by a simple open-ended question. Group II patients were asked first to quantitate the volume and frequency of their drinking. The outcome measures were the scores on the four CAGE questions recorded by an independent observer. RESULTS: Eighteen of 21 (86%) patients in Group I admitted to prior attempts to cut back on their drinking as compared with 8 of 22 (36%) in Group II (p = 0.002). Likewise 10 of 21 (49%) patients in the first group admitted to annoyance compared with just 3 of 22 (14%) in Group II. The average scores per patient in the two groups were significantly different: Group I = 2.52 versus Group II = 1.23 (p = 0.0002). Using a screening CAGE score of two or more to identify an alcoholic patient, the open-ended introduction identified 95% of the alcoholics compared with only 32% when the closed-ended introduction was used (p < 0.0001). CONCLUSION: Our study demonstrates that the sensitivity of the CAGE questionnaire in screening for alcoholism is dramatically enhanced by an open-ended introduction. In contrast, the sensitivity of these questions is greatly reduced when preceded by inquiries that seek to define the quantity and frequency of drinking. PMID- 8498398 TI - Iodide prophylaxis in Poland after the Chernobyl reactor accident: benefits and risks. PMID- 8498399 TI - Respiratory failure and eosinophilia in a young man. PMID- 8498400 TI - Long-term survival after fluconazole therapy of candidal prosthetic valve endocarditis. PMID- 8498401 TI - Importance of pathologic Q waves in patients with dilated cardiomyopathies. PMID- 8498402 TI - Post-traumatic stress disorder presenting as fibromyalgia. PMID- 8498403 TI - Erythermalgia secondary to vasculitis. PMID- 8498404 TI - Infective "mycotic" aortic root aneurysm following coronary artery bypass grafting. PMID- 8498405 TI - Correction of hyponatremia and development of central pontine myelinolysis. PMID- 8498406 TI - Hypoglycemia due to insulin autoantibody. PMID- 8498407 TI - Association of inflammatory bowel disease and bacterial endocarditis. PMID- 8498408 TI - Aldosterone secretion in patients treated with simvastatin and ACE inhibitors. PMID- 8498409 TI - Complications of fetal blood sampling. AB - To examine the incidence and significance of complications related to percutaneous fetal blood sampling, we reviewed all the articles published in the English literature on this procedure. Risks of complications and adverse outcomes depend mainly on the gestational age at the time of the procedure, the operator's experience, and the indication for the procedure. To determine the incidence of fetal losses, we pooled the data from series with > 100 cases. After exclusion of cases where some fetal pathologic condition was present, we determined the incidence of adverse outcomes in a low-risk population. In this population fetal blood sampling performed by an experienced operator carries about a 1.4% risk of fetal loss before 28 weeks' gestation and a 1.4% risk of perinatal death (after 28 weeks). PMID- 8498410 TI - Effect of advancing gestational age on the frequency of fetal ductal constriction in association with maternal indomethacin use. AB - OBJECTIVE: The objective of this study was to determine whether indomethacin is associated with an increased incidence of constriction of the human fetal ductus arteriosus with advancing gestational age. STUDY DESIGN: A retrospective analysis of fetal echocardiograms performed in 44 patients with premature labor or hydramnios treated with indomethacin (25 mg orally every 6 hours) was undertaken. Fisher's exact test, Kaplan-Meier survival analysis, and log-rank techniques were used; a value of p < 0.05 was considered statistically significant. RESULTS: The frequency of ductal constriction was similar for fetuses of singleton and multiple gestations. A dramatic increase in constriction was noted at 32 weeks' gestation when the rate of compromise approached 50%. CONCLUSIONS: The use of indomethacin should be restricted to gestational ages of < 32 weeks. In multiple gestations each fetus should be evaluated by echocardiography, because the ductal response may vary between individual fetuses. PMID- 8498411 TI - Frequency of glove perforations and subsequent blood contact in association with selected obstetric surgical procedures. AB - OBJECTIVE: One purpose of this prospective investigation was to assess the frequency of glove perforations and subsequent blood contact associated with selected obstetric procedures. The second purpose was to assess the relative risk of perforation among different members of the surgical team and determine if time of day or urgency of the procedure affected the frequency of perforation. STUDY DESIGN: Over a 3-month period, obstetric personnel were asked to double glove for all surgical procedures. After surgery, they placed their gloves in plastic bags and noted the type of procedure, time of day, and position on the surgical team. They also indicated whether they were aware of a glove tear and, if so, whether blood or fluid was on their hands. Gloves were tested for injury by two methods: by inflating them with air and subsequently immersing them in water to detect air bubbles and by directly filling them with water to observe for leaks. RESULTS: A total of 540 glove sets (2160 individual gloves) were examined; 407 sets were from cesarean deliveries, 65 from puerperal tubal ligations, and 68 from vaginal deliveries. Sixty-seven of the sets (12.4%, 95% confidence interval 9.6% to 15.2%) had at least one hole; the total number of holes was 78. Sixty-six holes were in the outer glove only, and 7 were in the inner glove only. In five sets (0.9%, 95% confidence interval 0.5% to 1.3%) there were matching holes in the outer and inner gloves. In two of these cases (0.4%, 95% confidence interval 0.1% to 0.7%) the surgeons noted blood on their hands at the conclusion of the procedure. The difference in frequency of injury in outer versus inner gloves was highly significant (p < 0.005). Forty-six of the 78 holes (59%) were on the thumb or first two fingers of the nondominant hand. Only 2 (3%) of the glove tears were recognized by the surgeon. There was no difference in frequency of glove tears when cesarean sections were classified as urgent versus nonurgent. There also was no difference in frequency of glove tears in procedures performed at night compared with those during the daytime. Surgical nurses had 36% of all glove injuries and were more likely than physicians or medical students to sustain perforations (p < 0.005). Primary surgeons and first assistants were more likely than second assistants to sustain glove injuries (p < 0.05). For primary surgeons and first assistants, level of training did not significantly affect the frequency of glove perforations. CONCLUSIONS: Glove perforations occur in approximately 12% of obstetric surgical procedures. Surgical nurses are at greatest risk for perforation. Double gloving reduces the likelihood of penetrating injury to the inner glove and subsequent risk of blood contact. PMID- 8498412 TI - Risk factors associated with uterine rupture during trial of labor after cesarean delivery: a case-control study. AB - OBJECTIVE: The purpose of our study was to thoroughly investigate the risk factors of uterine rupture in patients undergoing trial of labor after cesarean section. STUDY DESIGN: We conducted a case-control study of 70 patients with prior cesarean delivery with uterine rupture during trial of labor between January 1983 and June 1990. The risk factors of uterine rupture were identified, and the estimates of the relative risks were reported. RESULTS: The risk of uterine rupture was increased in patients who had an excessive amount of oxytocin, who had experienced dysfunctional labor, and who had a history of two or more cesarean deliveries. Epidural anesthesia, macrosomia, history of successful vaginal delivery after cesarean section, unknown uterine scar, and history of cesarean delivery because of cephalopelvic disproportion were not associated with uterine rupture. CONCLUSIONS: We recommend that all patients with a history of cesarean delivery be observed closely for progression of labor. Recognition of an active-phase arrest disorder, despite adequate augmentation with oxytocin, requires operative delivery. PMID- 8498413 TI - Fetal pancreatic beta-cell function in pregnancies complicated by maternal diabetes mellitus: relationship to fetal acidemia and macrosomia. AB - OBJECTIVE: Our purpose was to investigate the relationship between fetal pancreatic beta-cell function and fetal acidemia and macrosomia in pregnancies complicated by maternal diabetes mellitus. STUDY DESIGN: A cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, was performed. In 32 pregnancies complicated by maternal diabetes mellitus cordocentesis was performed at 36 to 39 weeks' gestation for the measurement of umbilical venous blood pH, PO2, PCO2, lactate, and glucose concentration; plasma insulin immunoreactivity; and insulin/glucose ratio. A reference range for plasma insulin and insulin/glucose ratio was constructed by studying fetal blood samples from 80 women who did not have diabetes mellitus. RESULTS: Mean umbilical venous blood pH was significantly lower and plasma insulin immunoreactivity and insulin/glucose ratio were significantly higher than the appropriate normal mean for gestation. There were significant associations between (1) maternal and fetal blood glucose concentrations (r = 0.95, p < 0.0001), (2) fetal blood glucose and plasma insulin immunoreactivity (r = 0.57, p < 0.01), (3) fetal plasma insulin immunoreactivity and blood pH (r = -0.39, p < 0.05), and (4) fetal insulin/glucose ratio and degree of macrosomia (r = 0.76, p < 0.0001). CONCLUSION: Fetal pancreatic beta-cell hyperplasia is implicated in the pathogenesis of both fetal acidemia and macrosomia. PMID- 8498414 TI - Deviation in amniotic fluid optical density at a wavelength of 450 nm in Rh immunized pregnancies from 14 to 40 weeks' gestation: a proposal for clinical management. AB - OBJECTIVES: Our purpose was to study deviations in values of amniotic fluid optical density at 450 nm in Rh-immunized pregnancies in the second and third trimesters and to propose a clinical management plan. STUDY DESIGN: A total of 789 amniotic fluid single and serial values of deviations in optical density at 450 nm were performed on Rh-immunized pregnancies from 14 to 40 weeks' gestation. The relationship of the deviations in amniotic fluid values of optical density at 450 nm to varying degrees of fetal disease were examined. RESULTS: In Rh-negative fetuses (unaffected) amniotic fluid values rise until 22 to 26 weeks before decreasing to term. In fetuses at risk of dying in utero, values are higher and trends rise. A clinical management plan was devised on the basis of the amniotic fluid findings of deviations in optical density at 450 nm. CONCLUSIONS: A clinical management scheme consisting of four zones is outlined. Rh-negative fetuses have minimal invasive procedures. Fetuses at risk of death undergo early cordocentesis for evaluation and therapy. Values that fall in between can be separated into two zones on the basis of the degree of risk. PMID- 8498415 TI - Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen/progesterone ratio of human fetal membranes at parturition. AB - OBJECTIVE: Our purpose was to measure the activity of the reversible enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase around parturition with estrogen and progestogen substrates. STUDY DESIGN: Classic kinetic studies and explant cultures were used to determine kinetic parameters and net enzyme activities in both oxidative and reductive directions for both sets of substrates. RESULTS: Affinity constant values for estrone, estradiol, and 20 alpha-dihydroprogesterone were 1 to 8 mumol/L. Affinity constant for progesterone was 9 to 25 mumol/L. Maximal velocities for all substrates in the chorion were 20- to 70-fold higher than in amnion and severalfold higher for estrogen substrates compared with the progestins. Around parturition there was a significant change toward net formation of the stronger estrogen (estradiol) and the weaker progestin (20 alpha dihydroprogesterone), suggesting an increase in the local estrogen/progesterone ratio. CONCLUSION: The enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase may be an important regulator of the local estrogen/progesterone ratio in fetal membranes around the time of parturition. PMID- 8498416 TI - Preservation of ovarian tissue in adnexal torsion with fluorescein. AB - OBJECTIVE: Our purpose was to assess the ability of fluorescein to intraoperatively detect viable fallopian and ovarian tissues involved in adnexal torsion. STUDY DESIGN: This prospective study was performed at Los Angeles County+University of Southern California Women's Hospital. Participants were female patients 18 to 45 years old with adnexal torsion confirmed at exploratory celiotomy. Five milliliters of 10% fluorescein were injected intravenously, and the involved untwisted adnexa was observed under ultraviolet light. Nonfluorescent tissue was resected and histologically evaluated. RESULTS: Eleven patients were entered into the study. Mean age was 25 years (range 15 to 42). Eight patients (72%) had preservation of involved ovarian tissue. No complications were associated with this procedure. Only three patients (28%) underwent oophorectomy. CONCLUSION: The use of intravenous fluorescein appears to be a valuable adjunct in the management of adnexal torsion. Application of this technique in reproductive-aged patients resulted in a three-quarter reduction in oophorectomy procedures. PMID- 8498417 TI - Postpartum depression and companionship in the clinical birth environment: a randomized, controlled study. AB - OBJECTIVE: Postpartum depression is a common feature of childbearing and is the cause of considerable morbidity. We have explored the possibility that clinically oriented care during labor may contribute to its occurrence. STUDY DESIGN: Of 189 nulliparous women laboring in a familiar community hospital, 92 were allocated by randomized, sealed envelopes to receive additional companionship from one of three volunteer labor companions recruited from the community. RESULTS: The group receiving support attained higher self-esteem scores and lower postpartum depression and anxiety ratings 6 weeks after delivery. CONCLUSION: In the clinical labor environment companionship modifies factors that contribute to the development of postnatal depression. We emphasize the importance of paying attention to the psychosocial environment in which labor takes place, to facilitate adaptation to parenthood. PMID- 8498418 TI - Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. AB - OBJECTIVE: Our objective was to characterize the short-term effects of maternal medications on breast-fed infants. STUDY DESIGN: A cohort of 838 infants breast fed by women who were taking medications was prospectively studied, and the incidence of adverse reactions in the infants during maternal therapy was recorded by telephone interviews. RESULTS: No major adverse reactions necessitating medical attention were observed in 838 breast-fed infants. However, 94 women (11.2%) reported infants' minor adverse reactions that did not require medical attention to the following maternal medications: (1) Antibiotics 19.3% (32/166); (2) analgesics or narcotics 11.2% (22/196); (3) antihistamines 9.4% (8/85); (4) sedatives, antidepressants, or antiepileptics 7.1% (3/42); and (5) others 9.9% (43/435). The most common minor adverse effects varies among drug categories, as follows: Antibiotics caused diarrhea (21/32); (2) analgesics or narcotics caused drowsiness (11/22); (3) antihistamines caused irritability (6/8); and (4) sedatives, antidepressants, or antiepileptics caused drowsiness (2/3). By identifying the 31 most frequently used drugs in our cohort, we have provided the first information on safety of breast-feeding during maternal therapy with such drugs as terfenadine, diphenhydramine, astemizole, dimenhydrinate, chlorpheniramine, 5-aminosalicylic acid, and alprazolam. CONCLUSIONS: The short-term effects, if any, of most maternal medications on breast-fed infants are mild and pose little risk to the infants. PMID- 8498419 TI - Single- and multiple-dose pharmacokinetics of a low-dose oral contraceptive in women with chronic renal failure undergoing peritoneal dialysis. AB - OBJECTIVE: Our purpose was to compare the pharmacokinetic parameters of oral administration of a 35 micrograms ethinyl estradiol, 1 mg norethindrone pill in peritoneal dialysis patients and normal women. STUDY DESIGN: A single-dose study was performed with five patients and four controls, followed by a multiple-dose study with five subjects in each group. Pharmacokinetic parameters were calculated by noncompartmental analysis and statistical analysis performed with Mann-Whitney U testing. RESULTS: There is no difference in the pharmacokinetic parameters for norethindrone in peritoneal dialysis patients compared with normal women. During multiple dosing an increased area under the concentration curve and decreased apparent oral clearance was observed for ethinyl estradiol in peritoneal dialysis patients compared with normal women. CONCLUSION: Peritoneal dialysis patients have decreased apparent oral clearance of ethinyl estradiol, leading to slightly higher serum concentrations compared with women with normal renal function. The clearance of norethindrone is the same in peritoneal dialysis patients and normal women. PMID- 8498420 TI - Fetal plasma interferon gamma concentration in normal pregnancy. AB - OBJECTIVE: Our purpose was to investigate changes with gestation in fetal plasma interferon gamma concentration. STUDY DESIGN: A cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, was performed. Enzyme-linked immunoassay was used to measure plasma concentration in 54 fetal blood samples obtained by cordocentesis or cardiocentesis at 12 to 37 weeks' gestation. RESULTS: The concentration of interferon gamma in fetal plasma decreased exponentially from a mean of 1.2 U/ml at 12 weeks' gestation to a mean of 0.5 U/ml at 37 weeks (r = 0.460, p < 0.001). CONCLUSIONS: The presence of high levels of fetal interferon gamma in the first trimester suggests that it may play an important role in early fetal immunologic development. Furthermore, this study has established reference ranges for interferon gamma that may be of value in the prenatal diagnosis of congenital infection. PMID- 8498421 TI - Dietary calcium and manganese effects on menstrual cycle symptoms. AB - OBJECTIVE: This exploratory study was designed to determine whether dietary calcium and manganese affect menstrual symptoms in healthy women. STUDY DESIGN: Ten women with normal menstrual cycles completed the Menstrual Distress Questionnaire each cycle during a 169-day, live-in metabolic study of calcium and manganese nutrition. Women were assigned in a double-blind, Latin-square manner to each of four 39-day dietary periods: 587 or 1336 mg calcium per day with 1.0 or 5.6 mg manganese per day. Responses were analyzed by repeated-measures analysis of variance. RESULTS: Increasing calcium intake reduced mood, concentration, and behavior symptoms generally (p < or = 0.05), reduced pain during the menstrual phase of the cycle (p = 0.034), and reduced water retention during the premenstrual phase (p = 0.041). In spite of increasing calcium intake, lower dietary manganese increased mood and pain symptoms during the premenstrual phase (p < or = 0.05). CONCLUSION: Dietary calcium and manganese may have a functional role in the manifestation of symptomatology typically associated with menstrual distress. PMID- 8498422 TI - The epidemiology of placenta previa in the United States, 1979 through 1987. AB - OBJECTIVE: Placenta previa can cause serious, occasionally fatal complications for fetuses and mothers; however, data on its national incidence and sociodemographic risk factors have not been available. STUDY DESIGN: We analyzed data from the National Hospital Discharge Survey for the years 1979 through 1987 and from the Retrospective Maternal Mortality Study (1979 through 1986). RESULTS: We found that placenta previa complicated 4.8 per 1000 deliveries annually and was fatal in 0.03% of cases. Incidence rates remained stable among white women but increased among black and other minority women (p < 0.1). In addition, the risk of placenta previa was higher for black and other minority women than for white women (rate ratio 1.3, 95% confidence interval 1.0 to 1.7), and it was higher for women > or = 35 years old than for women <20 years old (rate ratio 4.7, 95% confidence interval 3.3 to 7.0). Women with placenta previa were at an increased risk of abruptio placentae (rate ratio 13.8), cesarean delivery (rate ratio 3.9), fetal malpresentation (rate ratio 2.8), and postpartum hemorrhage (rate ratio 1.7). CONCLUSION: Our findings support the need for improved prenatal and intrapartum care to reduce the serious complications and deaths associated with placenta previa. PMID- 8498423 TI - Effects of maternal ingestion of low-dose aspirin on the fetal cardiovascular system. AB - OBJECTIVE: Our purpose was to assess fetal central and regional hemodynamics in normal fetuses using two-dimensional, range-gated pulsed Doppler echocardiography in pregnant women on chronic baby aspirin regimen (87 mg). STUDY DESIGN: Fifteen fetuses exposed to maternal chronic ingestion of baby aspirin were compared with 26 control fetuses. Longitudinal studies of the umbilical artery waveform and blood flow through the fetal right and left ventricles were obtained every 4 weeks during gestation in a group of fetuses exposed to daily maternal intake of 87 mg of aspirin. Pulsed Doppler waveforms were obtained below the tricuspid and mitral valves, at the level of the descending aorta (below the ductus), and at the level of the fetal renal artery as it enters the kidney. All tracings were recorded on a strip chart and analyzed with a digital light-pen and graphic overlay system. Peak systolic velocity and minimal diastolic velocity were obtained for the umbilical and fetal renal artery. Peak flow velocity and velocity time integral of the pulsed Doppler waveforms of the atrioventricular valves were calculated. Acceleration time/ejection time ratio was obtained for the descending aorta. RESULTS: No significant differences were found among the two groups in either central or regional circulation. CONCLUSION: Chronic daily maternal ingestion of baby aspirin does not significantly affect the central and regional circulation of the fetus. PMID- 8498424 TI - Detection of Chlamydia trachomatis by the polymerase chain reaction in the cervices of women with acute salpingitis. AB - OBJECTIVE: Our objective was to determine whether an increased prevalence of Chlamydia trachomatis could be detected by the polymerase chain reaction as opposed to culture in the cervices of women with acute salpingitis. STUDY DESIGN: Endocervical samples from 15 women with laparoscopy-verified acute salpingitis and 20 women seeking medical help for conditions other than pelvic pain were tested for Chlamydia trachomatis with the polymerase chain reaction. The oligonucleotide primer pairs used were specific for a 144 bp region of the major outer membrane protein that contained a single EcoRI endonuclease cleavage site. The detection of a 144 bp band that was cleaved by EcoRI to a 103 bp band denoted a Chlamydia trachomatis-positive sample. Cervical samples were cultured for Chlamydia trachomatis with the use of McCoy cells. The lymphocyte proliferative response to Chlamydia trachomatis elementary bodies was also determined. RESULTS: Nine of the 15 women (60%) with salpingitis had positive results when tested with the polymerase chain reaction for cervical Chlamydia trachomatis. Only two of these women (13%), both of whom had positive results when tested with the polymerase chain reaction, had cultures that were positive for Chlamydia trachomatis (p < 0.02). Among the 20 other women, only two patients with cervicitis had positive cultures for Chlamydia. Those women plus two women with unexplained recurrent abortions had positive polymerase chain reaction test results for Chlamydia trachomatis. A lymphocyte proliferative response to Chlamydia trachomatis was detected in five of eight women with salpingitis, as well as three of the other four patients, all of whom had positive polymerase chain reaction test results; lymphocytes from the remaining women were unresponsive. Follow-up cervical samples were obtained 4 to 6 months after treatment from six of the patients with salpingitis who had positive polymerase chain reaction test results; at that time five had negative polymerase chain reaction test results for Chlamydia trachomatis. CONCLUSION: The polymerase chain reaction appeared to be more sensitive and more rapid than culture in detecting Chlamydia trachomatis in the cervices of women with acute salpingitis. This assay may be of value for the early diagnosis of chlamydial infections. PMID- 8498425 TI - Emergency peripartum hysterectomy. AB - OBJECTIVES: By means of hospital-based data over 9 years we sought to evaluate the clinical indications and incidence of emergency peripartum hysterectomy by demographic characteristics and reproductive history. STUDY DESIGN: From the obstetric records of all deliveries at Brigham and Women's Hospital between Oct. 1, 1983, and July 31, 1991, we identified all women undergoing emergency peripartum hysterectomy, calculated crude and adjusted incidence rates, conducted statistical tests of linear trends and heterogeneity, and observed the clinical indications preceding the onset of this procedure. RESULTS: There were 117 cases of peripartum gravid hysterectomy identified during this period, for an overall annual incidence of 1.55 per 1000 deliveries. The rate increased with increasing parity and was significantly influenced by placenta previa and a history of cesarean section. The incidence by parity increased from one in 143 deliveries in nulliparous women with placenta previa to one in four deliveries in multiparous women with four or more deliveries with placenta previa. Likewise, the incidence increased from one in 143 deliveries in women with one prior live birth and a prior cesarean section to one in 14 deliveries in multiparous women with four or more deliveries with a history of a prior cesarean section. Both these trends were highly significant (p < 0.001). Abnormal adherent placentation was the most common cause preceding gravid hysterectomy (64%, p < 0.001), with uterine atony accounting for 21%. Although no maternal deaths occurred, maternal morbidity remained high, including postoperative infection in 58 (50%), intraoperative urologic injury in 10 patients (9%), and need for transfusion in 102 patients (87%). CONCLUSIONS: The data identify abnormal adherent placentation as the primary cause for gravid hysterectomy. The data also illustrate how the incidence of emergency peripartum hysterectomy increases significantly with increasing parity, especially when influenced by a current placenta previa or a prior cesarean section. Maternal morbidity remained high although no maternal deaths occurred. PMID- 8498426 TI - Meconium testing for cocaine metabolite: prevalence, perceptions, and pitfalls. AB - OBJECTIVES: We determined the prevalence of prenatal cocaine use in a racially mixed sample of urban and suburban mothers and correlated its use with maternal demographics and newborn measurements. STUDY DESIGN: Meconium from 621 consecutive newborns delivered at two university-affiliated urban hospitals were assayed for benzoylecgonine. Maternal and infant characteristics were linked anonymously with the results. Statistical analysis included t test, Fisher's exact test, Duncan's multiple range analysis, and analysis of covariance, with a value of p < 0.05 considered significant. RESULTS: We found that 3.4% of meconium samples had benzoylecgonine levels exceeding 0.1 micrograms/ml. Its presence was statistically correlated with maternal and neonatal characteristics. A nurse's opinion of cocaine use was correct 22% of the time. CONCLUSIONS: Prenatal cocaine use was statistically associated with multiparity, multigravidity, late-onset and clinic-based prenatal care, public assistance, nonwhite race, and low academic achievement. A nurse's opinion was a poor predictor of maternal cocaine use. Cocaine-exposed infants were significantly smaller, and this correlated best with nonwhite background. PMID- 8498427 TI - Detection of Chlamydia trachomatis in semen by the polymerase chain reaction in male members of infertile couples. AB - OBJECTIVE: Our objective was to evaluate the presence of asymptomatic Chlamydia trachomatis infection by means of the polymerase chain reaction in male members of couples with previously undiagnosed infertility. STUDY DESIGN: Twenty-eight infertile-couples who had negative cultures or negative results when tested by deoxyribonucleic acid probe for Chlamydia trachomatis in semen and cervical samples were studied. Semen samples were tested for Chlamydia trachomatis by means of the polymerase chain reaction. Sera from both partners were diluted 1:128 and tested for immunoglobulin M antibodies to Chlamydia. Sera and ejaculated sperm were evaluated for the presence of antisperm antibodies. Semen analyses were also performed. RESULTS: Chlamydia trachomatis was identified in semen from 11 (39.3%) of the male partners. Its detection correlated with the presence in the ejaculate of motile sperm containing antisperm antibodies (p < 0.01). Either antisperm immunoglobulin G, immunoglobulin A, or both were located on sperm only from 5 (45.5%) of the 11 men whose results were positive when tested for Chlamydia trachomatis. Similarly, immunoglobulin G or immunoglobulin A antibodies to sperm were only detected in 5 (45.5%) of the spouses of men with Chlamydia in semen. Immunoglobulin M antibody to Chlamydia trachomatis was identified in only one of the men. However, antichlamydial immunoglobulin M antibodies were present in sera from 6 (54.5%) female partners of men with seminal Chlamydia trachomatis but in none of the other 17 women (p < 0.01). CONCLUSION: Although undetected by culture of deoxyribonucleic acid probe of semen samples, Chlamydia trachomatis was nevertheless identified in semen of some symptom-free men by the polymerase chain reaction. This is probably a result of the increased sensitivity of the polymerase chain reaction to detect Chlamydia trachomatis. The increased prevalence of an autoimmune response to sperm in men with this organism in their semen suggests that a subclinical chlamydial infection may activate an immune response to sperm. A similar association between Chlamydia trachomatis in semen and circulating antisperm antibodies in female partners indicates that Chlamydia may also induce an immune response to sperm in women. Infertility in these couples may be the result of a direct inflammatory response in the cervix or endometrium to repeated Chlamydia exposure or of the ability of Chlamydia to evoke an immune response to spermatozoa. PMID- 8498429 TI - Clinical characteristics and outcome of twin gestation complicated by preterm premature rupture of the membranes. AB - OBJECTIVE: Our purpose was to report the clinical characteristics and outcome of twin pregnancy complicated by preterm premature rupture of membranes. STUDY DESIGN: Pregnancy outcome is compared between 99 twin pregnancies and 99 well matched singleton pregnancies complicated by preterm rupture of the membranes. RESULTS: Preterm premature rupture of membranes occurs more frequently in twin than singleton gestations (7.4% vs 3.7%, p < 0.001, odds ratio 2.1). Midtrimester premature rupture of membranes (< 26 weeks' gestation) complicated 1.37% of twin gestations (18.2% of those with preterm premature rupture of membranes) versus 0.52% of singleton gestations (p < 0.001, odds ratio 2.71). The mean gestational age at preterm premature rupture of membranes was 30.1 +/- 4.3 weeks. The median latency to delivery for twins was 1.1 days with 91% of patients delivered within 7 days (vs 1.7 days, 90% delivered at 7 days for singleton gestations). Latency was prolonged with preterm premature rupture of membranes < 30 weeks' versus > or = 30 weeks' gestation (p = 0.03). The nonpresenting infant more frequently had hyaline membrane disease and required more oxygen therapy than the presenting infant. No significant differences in infectious morbidity, cord prolapse, or abruptio placentae were seen between twin and singleton gestations. CONCLUSION: This investigation provides the basis for patient counseling and management subsequent to preterm premature rupture of membranes in twin gestation. PMID- 8498428 TI - Association between pregnancy-induced hypertension and asthma during pregnancy. AB - OBJECTIVE: Pregnancy-induced hypertension is an important cause of maternal mortality, intrauterine growth retardation, and perinatal mortality. We examined the relationship between pregnancy-induced hypertension and asthma. STUDY DESIGN: The study population consisted of 24,115 women without a history of chronic systemic hypertension who were delivered of live born and stillborn infants at Mount Sinai Medical Center between January 1987 and December 1991. Pregnancy induced hypertension was defined as blood pressure of at least 140/90 mm Hg or an increase of > or = 30 mm Hg in systolic pressure or > or = 15 mm Hg in diastolic pressure. RESULTS: There was a significant association between pregnancy-induced hypertension and asthma during pregnancy (chi 2 = 17.86, p < 0.001). In addition, there was a significant upward trend in the incidence of asthma during pregnancy in women without, with moderate, and with severe pregnancy-induced hypertension (Mantel-Haenszel chi 2 = 11.8, p = 0.001). Logistic regression analysis demonstrated that the association between pregnancy-induced hypertension and asthma during pregnancy persisted after adjustment for the confounding factors of race or ethnicity, maternal age, parity, and prepregnancy weight (adjusted odds ratio 2.52, 95% confidence interval 1.47 to 4.35, p = 0.0008). An association between pregnancy-induced hypertension and a history of asthma was also found (chi 2 = 11.2, p = 0.001). However, after adjustment for potential confounders, this association failed to achieve statistical significance (adjusted odds ratio 1.2, 95% confidence interval 0.97 to 1.53, p = 0.083). CONCLUSION: Both pregnancy induced hypertension and asthma might be caused by a third factor affecting smooth muscle reactivity. PMID- 8498430 TI - Hormone replacement therapy and risk of breast cancer: results from epidemiologic studies. AB - OBJECTIVE: We combined data from published reports of the relation between estrogen use and breast cancer. We specifically addressed the hypothesis that the addition of progestins to estrogen therapy reduces the risk of breast cancer. STUDY DESIGN: A meta-analysis was performed. RESULTS: Replacement hormone therapy is not associated with increased risk of breast cancer in women who have ever used it (relative risk 1.02, 95% confidence interval 0.93 to 1.12). However, current use is associated with increased risk (relative risk 1.40, 95% confidence interval 1.20 to 1.63). Although there was no significant trend with increasing duration of use, women with > or = 10 years of estrogen use had a relative risk of 1.23 (95% confidence interval 1.08 to 1.40). However, data on use of estrogen plus progestins combined from four studies indicate that risk is not reduced and that the overall relative risk is 1.13 (95% confidence interval 0.78 to 1.64). Further, risk did not vary in strata of family history or benign breast disease. CONCLUSION: Although these results exclude a large effect of hormone therapy on risk of breast cancer, we are unable to rule out some risk associated with current or long-term estrogen use. PMID- 8498431 TI - Does "idiopathic" preterm labor resulting in preterm birth exist? AB - OBJECTIVE: In an effort to elucidate possible causes of preterm labor, we undertook a prospective study of 50 patients consecutively admitted with intact membranes and preterm labor who eventually had a preterm delivery despite the use of tocolysis. STUDY DESIGN: A comprehensive evaluation plan was instituted. This included a detailed history and physical examination, targeted ultrasonography, amniocentesis for Gram stain, culture, and glucose determination, laboratory analysis for infection (complete blood cell count, urinalysis, and cervical and urine cultures) and for antiphospholipid antibody syndrome (antinuclear antibody, lupus anticoagulant, anticardiolipin antibody), pathologic examination of the placenta, and a urine toxicology screen. RESULTS: The following groups of possible causes of preterm labor were identified: (1) faulty placentation, 50% (25/50); (2) intrauterine infection 38% (19/50); (3) immunologic factors, 30% (15/50); (4) cervical incompetence, 16% (8/50); (5) uterine factors, 14% (7/50); (6) maternal factors 10% (5/50); (7) trauma and surgery, 8% (4/50); (8) fetal anomalies, 6% (3/50); and (9) idiopathic conditions, 4% (2/50). Among the 50 patients two or more possible causes were identified in 58% (29/50). CONCLUSION: We suggest that an exhaustive evaluation plan can identify possible causes in the majority (96%) of cases of "idiopathic" preterm labor that result in preterm delivery. PMID- 8498432 TI - The use of saline solution as a contrast medium in suspected diaphragmatic hernia and renal agenesis. AB - OBJECTIVE: Our purpose was to determine the value of saline solution instillation as a contrast medium in suspected congenital diaphragmatic hernia and renal agenesis. STUDY DESIGN: Intrathoracic (n = 3) or intraperitoneal (n = 2) instillation was performed in five cases of suspected congenital diaphragmatic hernia. Amnioinfusion combined with intraperitoneal instillation was performed in five cases of suspected renal agenesis. RESULTS: Instillation clearly demonstrated the diaphragmatic defect in four of the five cases. In the cases with suspected renal agenesis, amnioinfusion led to recognition of a previously unsuspected sirenomelia, and intraperitoneal instillation demonstrated empty renal fossae in four cases. The final fetus with bilateral renal agenesis was thought antenatally to have a contralateral multicystic kidney. CONCLUSIONS: We suggest that intrathoracic or intraperitoneal saline solution instillation is a useful diagnostic procedure in carefully selected cases where confident ultrasonic diagnosis is often difficult and yet would significantly alter management. In cases of severe oligohydramnios amnioinfusion is a complementary procedure. In 80% of cases in this series there was significant improvement in visualization after the procedure. PMID- 8498433 TI - Incisional hernias after major laparoscopic gynecologic procedures. AB - OBJECTIVE: Our purpose was to determine the incidence of incisional hernias after operative laparoscopy. STUDY DESIGN: A retrospective case review was performed. RESULTS: The frequency of incisional hernias at extraumbilical 10 and 12 mm trocar insertion sites was one in 429 (0.23%) cases and five in 161 (3.1%) cases, respectively; the difference is statistically significant (p = 0.007, Fisher's exact test). Incisional hernias were also significantly more common if the fascia was left open (p = 0.021), although three of the five hernias at 12 mm trocar sites occurred after attempted closure of the underlying fascia. CONCLUSION: The underlying fascia should be closed whenever a 10 mm or larger trocar is placed at an extraumbilical site during laparoscopy. The peritoneum may also require closure at 12 mm trocar sites if the trocar is placed through, rather than lateral to, the rectus sheath. PMID- 8498434 TI - Dynamic ultrasonographic imaging of the third stage of labor: new perspectives into third-stage mechanisms. AB - OBJECTIVE: Dynamic ultrasonographic imaging of the third stage of labor was performed to document ultrasonographic findings and to present new perspectives into third-stage mechanisms. STUDY DESIGN: Twenty-five normal deliveries and five with prolonged third-stage labor were studied. RESULTS: Normal third-stage labor could be divided into four phases: (1) latent phase, characterized by thick, placenta-free wall and thin, placenta-site wall; (2) contraction phase, with thickening of placenta-site wall (from < 1 cm to > 2 cm); (3) detachment phase, in which the placenta completes its separation and detaches; and (4) expulsion phase, with a sliding movement of the placenta. Although oxytocic agents were routinely used, they do not seem to influence the findings. In five cases with retained placenta the placenta-site wall was initially thin. In four of them it became thick, and the placenta was removed by traction of the cord, whereas in the fifth case the placenta-site wall remained thin and the placenta had to be removed manually. CONCLUSION: Shearing forces seem to tear the decidual septae and thereby separate the placenta. This process is completed only when the placenta-site wall attains full thickness. In cases of prolonged third-stage labor, traction of the cord should be applied only when this phase is completed and the actual sliding movement of the placenta is observed. PMID- 8498435 TI - Twin gestation: fetal presentation as a function of gestational age. AB - OBJECTIVE: Our objective in this study was to evaluate the rate of spontaneous version in twin gestation throughout the third trimester. STUDY DESIGN: Serial ultrasonographic examinations were performed on 119 consecutive patients with twin gestation. The incidence of spontaneous version as a function of gestational age was calculated. RESULTS: The mean birth weight and gestational age at delivery were 2640 gm and 37 weeks, respectively. Nineteen percent had birth weight discordancy, and 37% were delivered by cesarean section. The incidence of spontaneous version decreased from 60% at 28 to 30 weeks' gestation to 25% to 30% at term. The lowest incidence of spontaneous version was observed in pregnancies with a cephalic-cephalic presentation (7%). All other presentations were relatively unstable. Neither the patients' parity nor the presence of birth weight discordancy, the placental location, or the amniotic fluid volume had a significant association with the incidence of spontaneous version. CONCLUSION: These data should be incorporated into the routine antepartum counseling of patients with twin gestation. Their use in this capacity may result in a decreased cesarean delivery rate if clinicians realize that malpresentations may spontaneously resolve before the onset of labor. PMID- 8498436 TI - Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. AB - OBJECTIVE: We evaluated the relationship between delayed care of symptomatic pelvic inflammatory disease and impaired fertility. STUDY DESIGN: We used data from a cohort of women with clinically recognized pelvic inflammatory disease. Case patients were women with either ectopic pregnancy or infertility (n = 76); controls were women with intrauterine pregnancies (n = 367). RESULTS: Women who delayed seeking care for pelvic inflammatory disease were three times more likely to experience infertility or ectopic pregnancy than women who sought care promptly after adjustment for age, organism, year of diagnosis, and history of recent gynecologic events (95% confidence interval = 1.27, 6.11). This association was strongest for women with chlamydia; 17.8% (18/101) of those who delayed seeking care had impaired fertility, whereas 0.0% (0/13) of those who sought care promptly suffered known sequelae. CONCLUSIONS: Women with pelvic inflammatory disease who delay seeking care are at increased risk for infertility and ectopic pregnancy. Furthermore, our data suggest that prompt evaluation and treatment of chlamydial pelvic inflammatory disease can prevent these sequelae. PMID- 8498437 TI - A comparison of visual and automated methods of analyzing fetal heart rate tests. AB - OBJECTIVES: Our objective in this study was to compare evaluation and clinical implications of visual versus computerized analysis of nonstress tests. METHODS: Nonstress tests of 575 high-risk patients were analyzed visually and by a computer using the Oxford Sonicaid System 8000. Standard reactivity criteria were used for visual assessment; the System 8000 used an algorithm with the Dawes Redman criteria. RESULTS: Ninety-six percent of nonstress tests that met Dawes Redman criteria were reactive by visual analysis; 93% of reactive nonstress tests met Dawes-Redman criteria. Only 30% of tests that failed Dawes-Redman criteria were nonreactive, whereas 44% of nonreactive tests failed to meet Dawes-Redman criteria. Sensitivities, specificities, and positive and negative predictive values were similar for both approaches. Additional tests or interventions would have occurred in 9% of the cases analyzed by System 8000 and in 49% of the cases analyzed visually. CONCLUSIONS: Although these approaches rate nonstress tests differently, their diagnostic performances are similar. Automated fetal heart rate testing may become an acceptable alternative to conventional visual analysis. PMID- 8498438 TI - Comparative analysis of progesterone and placental protein 14 measurements in the evaluation of luteal function. AB - OBJECTIVE: Our purpose was to investigate the diagnostic accuracy of single or summed measurements of progesterone and placental protein 14, a progestin dependent endometrial glycoprotein, in the evaluation of luteal function. STUDY DESIGN: Forty-five healthy women had daily blood measurements of luteinizing hormone, progesterone, and placental protein 14 during one menstrual cycle. RESULTS: Thirty-nine women had normal and six had deficient luteal function on the basis of serial progesterone determinations. Luteal insufficiency was not accurately diagnosed by single progesterone or placental protein 14 values or by integrated placental protein 14 measurements. In contrast, the condition was correctly identified in all but one cycle when the sum of progesterone on days 4 and 7 was < 49 nmol/L (15.4 ng/ml). A poor correlation was found between peak or integrated measurements of progesterone and placental protein 14. CONCLUSION: Measurement of serum progesterone, but not placental protein 14, on 2 days of the midluteal phase provides a convenient and reliable test of luteal function. PMID- 8498439 TI - Flow cytometric crossmatch and early pregnancy loss in women with a history of recurrent spontaneous abortions who underwent paternal leukocyte immunotherapy. AB - OBJECTIVE: The purpose of our study was to evaluate the clinical significance of flow cytometric crossmatch in managing women with unexplained recurrent spontaneous abortions who have been immunized with paternal leukocytes. STUDY DESIGN: Two-color flow cytometric crossmatch was performed after immunotherapy in 69 women with recurrent spontaneous abortions to detect maternal immunoglobulin G antibodies against paternal T lymphocytes. A positive flow cytometric crossmatch was determined by a > or = 20 channel increases (256 channel linear scale-log amplification) in the fluorescence intensity of the T-cell peak. We analyzed the clinical correlation between flow cytometric crossmatch results and subsequent pregnancy outcome in those patients using the Fisher exact test. RESULTS: In 46 subsequent pregnancies among 69 immunized women the incidence of early subsequent pregnancy wastage was only 6 (17.1%) of 35 in flow cytometric crossmatch-positive patients and 7 (63.6%) of 11 in flow cytometric crossmatch-negative patients (p < 0.01). CONCLUSIONS: These data indicate that a two-color T cell flow cytometric crossmatch predicts subsequent pregnancy outcome in patients undergoing immunotherapy for recurrent spontaneous abortion. PMID- 8498440 TI - Umbilical and placental vessels: modifications of their mechanical properties in preeclampsia. AB - OBJECTIVES: Our objective in this study was to assess the basic mechanical properties of umbilical and chorionic vessels of placentas delivered after both normal and preeclamptic pregnancies. STUDY DESIGN: Placentas were selected when the parturient women were admitted to the delivery room. Normal pregnancy (n = 17) was characterized by delivery at term (38 to 40 weeks) after uncomplicated pregnancy without any medication. Preeclamptic pregnancy (n = 7) was characterized by delivery after 28 weeks of pregnancy (28 to 39 weeks) after sustained hypertension and proteinuria. Arteries and veins from the umbilical cord and chorionic plate were prepared in rings for in vitro study in tissue baths. Passive and active (on stimulation by potassium chloride or serotonin) mechanical properties of these vessels were studied. RESULTS: In vessels from normal pregnancy, responsiveness, but not sensitivity, was increased with increasing passive tension on vessels until optimal tension was reached. The passive stretch-tension curve was shifted downward in umbilical veins and upward in umbilical arteries and chorionic veins obtained from preeclamptic mothers in comparison with normal parturient women. In the absence of passive tension, contractions in response to potassium chloride were produced in all umbilical veins and some chorionic veins from preeclampsia but not from normal pregnancy. Developed wall tension curves in chorionic vessels from preeclampsia were shifted upward. In umbilical veins and arteries and in chorionic veins, the optimal passive tension was lower in tissues from preeclampsia than in tissues from normal pregnancy. CONCLUSION: Our results indicate that both passive and active mechanical properties of umbilical vessels are modified after pregnancy complicated by preeclampsia. PMID- 8498441 TI - Sex chromosome composition of complete hydatidiform moles: relationship to metastasis. AB - OBJECTIVE: Complete hydatidiform moles have a substantial risk for subsequent development of persistent or metastatic gestational trophoblastic tumor. We evaluated the hypothesis that presence of a Y chromosome in a complete hydatidiform mole confers an increased risk for developing metastatic gestational trophoblastic tumor. STUDY DESIGN: The polymerase chain reaction was applied to archival paraffin-embedded molar-tissue to identify Y chromosome-positive dispermic moles in patients who did or did not develop metastatic disease. To reduce the chances of analytic error, consensus polymerase chain reaction primers directed at homologous but different genes present on both X and Y chromosomes were used. RESULTS: Y-chromosome sequences were identified in 7.7% (1/13) of the metastatic group and 9.1% (2/22) of the nonmetastatic group, a statistically insignificant difference. CONCLUSION: We are unable to confirm any increased risk for metastasis in Y chromosome-positive compared with Y chromosome-negative complete hydatidiform mole. PMID- 8498442 TI - Transabdominal thin-gauge embryofetoscopy: a technique for early prenatal diagnosis and its use in the diagnosis of a case of Meckel-Gruber syndrome. AB - OBJECTIVE: Our aim was to develop and evaluate a transabdominal endoscopic technique to visualize the embryo or fetus with thin-gauge needles and submillimetric fiberoptic endoscopes. METHODS: Under ultrasonographic guidance, an 18- or 19-gauge thin-wall needle was introduced into the uterus of 28 patients undergoing first-trimester or early second-trimester termination of pregnancy. A 0.7 mm endoscope was threaded through the lumen of the needle after removal of the stylet. Visualization of the embryo-fetus was attempted before 14 weeks' gestation (n = 20). From 16 to 20 weeks (n = 8), the needle and endoscope were directed to the placental insertion of the umbilical cord, and a cordocentesis was performed. RESULTS: Excellent visualization of the surface anatomy of fetuses from 7 to 13 weeks was obtained in 85% of cases (17/20). A diagnosis of Meckel Gruber syndrome was made at 11 weeks' menstrual age by visualizing postaxial polydactyly and an occipital encephalocele. Endoscopically assisted cordocentesis allowed visualization of the lumen of the umbilical vein and of the blood flow within it. CONCLUSION: Endoscopic visualization of the embryo or fetus can be performed transabdominally in the first trimester with small-delivered endoscopes. This represents a clear advantage over previous endoscopic approaches to the human pregnancy. Potential applications of this technique include a precise description of fetal anatomy and physiologic features, diagnosis of anomalies, and therapeutic fetal interventions. PMID- 8498443 TI - Maternal and fetal cardiorespiratory responses to adenosine in sheep. AB - OBJECTIVE: We determined the cardiorespiratory effects of maternal adenosine administration on the ewe and fetus. STUDY DESIGN: Adenosine was infused intravenously to five pregnant ewes as graded (25 to 400 micrograms/min per kilogram) and constant (200 micrograms/min per kilogram) infusions and as a single injection (200 micrograms/kg). Heart rate, arterial pressure, and arterial blood gases and pH were monitored in the ewe and fetus; the data were analyzed with two-way analysis of variance with Duncan's test. RESULTS: Graded adenosine infusion produced a dose-dependent rise in maternal heart rate and hemoglobin concentration and a fall in diastolic and mean arterial pressures, effects that were maintained during 1 hour of constant infusion. Single injections transiently lowered diastolic pressure and induced a biphasic change in heart rate consisting of a bradycardia followed by a tachycardia with a return to control values. Adenosine administration to the ewe did not affect maternal arterial blood gases and systolic pressure nor alter fetal heart rate, arterial pressure, or arterial blood gases. CONCLUSION: Although adenosine causes cardiovascular changes in pregnant ewes, the effects are well tolerated and do not significantly affect the cardiorespiratory status of the fetus. PMID- 8498444 TI - Ontogeny of angiotensin II vascular smooth muscle receptors in ovine fetal aorta and placental and uterine arteries. AB - OBJECTIVE: Our purpose was to determine if differences in angiotensin II vascular smooth muscle receptor binding account for the attenuated fetal placental and systemic responses to infused angiotensin II relative to maternal responses and for the differences between umbilical and fetal systemic responses. STUDY DESIGN: Using plasma membranes prepared from the medial layer of fetal aorta, fetal placental artery, and maternal uterine artery obtained between 107 and 134 days of ovine gestation (n = 17), we measured and compared angiotensin II receptor binding density (in femtomoles per milligram of protein) and affinity (in nanomoles per liter) in radioligand binding studies with iodine 125-angiotensin II. Maternal and fetal plasma angiotensin II were also compared. RESULTS: A single class of high-affinity receptor was identified in all arteries. Although the binding density was similar at < 100 and > 130 days for fetal aorta (388 +/- 87 [SE] vs 262 +/- 56), placental artery (319 +/- 95 vs 235 +/- 54), and uterine artery (46 +/- 6 vs 50 +/- 13), values for fetal arteries exceeded those for uterine arteries (p < or = 0.018) in spite of higher fetal plasma angiotensin II (74 +/- 18 vs 30 +/- 8 pg/ml, p < 0.01). Affinity did not differ between arteries and, except for fetal aorta (1.4 +/- 0.2 vs 2.1 +/- 0.4, r = 0.49, p = 0.045), was unchanged during late gestation. CONCLUSION: Differences between fetal and maternal responses and fetal placental and systemic responses to infused angiotensin II in sheep do not reflect alterations in total angiotensin II vascular smooth muscle receptor binding density or affinity. PMID- 8498445 TI - Effects of labetalol on uterine blood flow and cardiovascular hemodynamics in the hypertensive gravid baboon. AB - OBJECTIVE: The purpose of this study was to investigate the effects of labetalol on uterine blood flow and cardiovascular parameters in acutely instrumented, hypertensive gravid baboons. STUDY DESIGN: During the latter half of pregnancy six gravid baboons were acutely instrumented, with ultrasonic flow probes placed on ipsilateral, external iliac, and uterine arteries and a flow-directed pulmonary artery catheter in the pulmonary artery. After a stable arterial pressure baseline was obtained, norepinephrine was infused to increase mean arterial pressure by at least 20%. A 20-minute hypertensive steady state was obtained. Labetalol at 0.5 and 1.0 mg/kg was randomly infused, followed by a 2.0 mg/kg dose, each over 1 minute. A 20-minute recovery period followed every labetalol infusion, allowing the hypertensive steady state to reestablish. External iliac and uterine blood flow measurements were continuously recorded during the baseline and experimental trials. Mean arterial blood pressure, heart rate, pulmonary artery and capillary wedge pressure, central venous pressure, and cardiac output were obtained at 5, 10, and 15 minutes during each steady state and after each labetalol infusion. RESULTS: Labetalol at all dosages significantly reduced the mean arterial pressure and the systemic vascular resistance at 1.0 and 2.0 mg/kg. External iliac blood flow was not consistently significantly reduced; however, uterine blood flow was significantly reduced after the 1.0 and 2.0 mg/kg labetalol dosages (p < 0.05). Although uterine vascular resistance tended to increase after the 1.0 and 2.0 mg/kg doses, statistical significance was not achieved. CONCLUSION: Low-dose labetalol (0.5 mg/kg) significantly reduces the pharmacologic hypertensive gravid baboon's mean arterial blood pressure without adversely affecting uterine blood flow. PMID- 8498446 TI - Selecting human chorionic gonadotropin immunoassays: consideration of cross reacting molecules in first-trimester pregnancy serum and urine. AB - OBJECTIVE: We investigated the variation in human chorionic gonadotropin results found with different commercial kits. Levels of human chorionic gonadotropin and related molecules were determined in pregnancy serum and urine and compared with the specificities of different laboratory, office, and home test kits. STUDY DESIGN: Total human chorionic gonadotropin (nicked+nonnicked), nonnicked human chorionic gonadotropin, free beta subunit, and beta core fragment were measured in 242 serum samples and 125 urine samples from early pregnancies. RESULTS: In serum, in the 2 weeks after the missed period when most pregnancy tests are performed, median levels of total, nonnicked, and beta human chorionic gonadotropin (total+free beta+beta core) were similar (< or = 12% difference). Individual values, however, varied significantly. For nonnicked human chorionic gonadotropin, values ranged from 41% to 145% and for beta from 101% to 145% of the total human chorionic gonadotropin level. In urine individual nonnicked values varied from < 1% to 148% and beta values from 102% to 547% of the total human chorionic gonadotropin level. A survey of 29 kits revealed that 10 were types detecting total human chorionic gonadotropin, five detecting nonnicked only, and 14 were beta assays. CONCLUSIONS: Results from total, nonnicked, and beta human chorionic gonadotropin kits are not necessarily interconvertible. Individual variations in levels of nicked human chorionic gonadotropin, free beta and beta core, and differences in their recognition by immunoassays causes discordant results. PMID- 8498447 TI - Augmentation of polynuclear aromatic hydrocarbon metabolism of human placental tissues of first-trimester pregnancy by cigarette smoke exposure. AB - OBJECTIVE: Polynuclear aromatic hydrocarbons are important components of cigarette smoke. The toxicity of polynuclear hydrocarbons depends on their metabolic biotransformation by tissues. This study was performed to assess the effects of cigarette smoke exposure on polynuclear aromatic hydrocarbon metabolism in the human placental tissues of first-trimester pregnancy. STUDY DESIGN: The expression of essential enzymes that metabolize polynuclear aromatic hydrocarbons and regulate toxic metabolism, aryl hydrocarbon hydroxylase, epoxide hydrolase, and glutathione S-transferase, were determined by immunocytochemical staining of the specific enzymes in first-trimester placental samples from both smoker and nonsmoker donors. The overall polynuclear aromatic hydrocarbon metabolism by such tissues was quantitated by a radiometric assay with benzo[a]pyrene substrate in placental villi tissues and also in isolated trophoblast cells or in cultured trophoblast cells in the presence of polynuclear aromatic hydrocarbon agent. RESULTS: Immunocytochemical staining revealed that aryl hydrocarbon hydroxylase was localized on trophoblast cells of first trimester placentas from smoker donors. Epoxide hydrolase was present in stromal and trophoblast cells, and glutathione S-transferase (pi) was present in trophoblast cells of both nonsmoker and smoker subjects. In addition, the overall metabolism of polynuclear aromatic hydrocarbon xenobiotics in such tissues (8 to 11 weeks) of donors who smoked cigarettes was observed to be increased compared with that of nonsmokers by radiometric assay of metabolic products. The increased polynuclear aromatic hydrocarbon metabolism from such exposure was also shown in isolated and purified trophoblast cells of first-trimester placental villi and in culture of such trophoblast cells of nonsmoker donors with polynuclear aromatic hydrocarbon by the same assay procedure. CONCLUSIONS: Therefore, contrary to previous assumptions, these data demonstrate that cigarette smoke exposure increases the polynuclear aromatic hydrocarbon metabolism of placentas even during the early stages of pregnancy. Augmented polynuclear aromatic hydrocarbon metabolism may produce genotoxic metabolites deleterious to conceptus development. PMID- 8498448 TI - Collagenase, its inhibitors, and decorin in the lower uterine segment in pregnant women. AB - OBJECTIVE: It is postulated that collagenase activity in the cervix and lower uterine segment is important for dilatation at the time of labor. If so, the enzyme must partially escape from control by inhibitors. A second hypothesis is that an elevated ratio of decorin (dermatan sulfate proteoglycan) to collagen may also contribute to the dilatation process. STUDY DESIGN: The activity of collagenase, its natural inhibitors (tissue inhibitor of metalloproteinase-1 and alpha 2-macroglobulin), elastase, hydroxyproline (collagen), and decorin were quantified in biopsies of the lower uterine segment at term (not dilated) and during active labor. RESULTS: Collagenase concentration is 23 times higher in the cervix of patients in labor than at term. The sum of alpha 2-macroglobulin plus tissue inhibitor of metalloproteinase-1 increased only twofold in labor, as did elastase. The ratio of decorin to collagen doubled. CONCLUSION: The imbalance caused by collagenase increasing much more than its inhibitors may contribute to collagen breakdown and dilatation. Neutrophils may be responsible for much of this increase of collagenase. The increased ratio of decorin to collagen supports the hypothesis that the interaction of these two components is important in dilatation. PMID- 8498449 TI - Effect of rapid intravenous crystalloid infusion on uteroplacental blood flow and placental implantation-site oxygen delivery in the pregnant ewe. AB - OBJECTIVE: Our purpose in this study was to investigate the effects of rapid intravenous crystalloid infusion on placental implantation-site blood flow and oxygen delivery in the near-term pregnant ewe. STUDY DESIGN: Maternal left ventricular, femoral arterial and venous, and bilateral fetal hind limb arterial catheters were placed in nine near-term ewes 5 days before the start of the study. Maternal and fetal arterial blood gas values, maternal hemodynamic measurements, and maternal organ blood flows (microsphere technique) were obtained before and after the intravenous infusion of 2.0 to 2.5 L of normal saline solution. Myometrial and placental implantation-site vascular resistances and oxygen delivery were calculated. The t test for paired comparisons was used for statistical analysis, with p < or = 0.05 considered significant. RESULTS: Significant postinfusion increases in maternal mean arterial pressure, placental implantation-site blood flow, and skin, skeletal muscle, and renal blood flows were recorded. In the six animals that demonstrated a fall in hemoglobin concentration, a significant increase in placental implantation-site oxygen delivery and a significant decrease in placental implantation-site vascular resistance were also seen. No significant changes were seen in myometrial blood flow or myometrial vascular resistance. CONCLUSION: Rapid intravenous crystalloid infusion selectively increases placental implantation-site blood flow in the near term pregnant ewe and may improve oxygen delivery to the fetus, especially if hemodilution occurs. PMID- 8498450 TI - Gestational diabetes alters human placental vascular responses to changes in oxygen tension. AB - OBJECTIVE: Our objective was to study tone responses caused by hypoxia, reoxygenation, and hydrogen peroxide in human placental vessels from gestational diabetic and normal term pregnancies. STUDY DESIGN: Isolated placental arteries and veins from women with well-controlled gestational diabetic and uncomplicated term pregnancies were precontracted with U46619 under 5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) and then exposed to hypoxia (95% nitrogen/5% carbon dioxide) atmosphere (PO2 8 to 10 torr) for 5 to 7 minutes followed by rapid reoxygenation. Cumulative doses of hydrogen peroxide (1 to 100 mumol/L) were added at 2-minute intervals. The studies were conducted in both the presence and the absence of endothelium. Prostaglandin involvement was examined by treatment with indomethacin. Analysis of variance and t test statistics were used. RESULTS: After incubation under 5% oxygen, hypoxia caused a larger prostaglandin-independent relaxation in arteries and veins of women with gestational diabetes than in normal vessels. Placental vessels of women with gestational diabetes were found to undergo a significantly larger contraction than normal vessels when exposed to posthypoxic reoxygenation or micromolar concentrations of hydrogen peroxide. Both responses were eliminated and reversed to a relaxation by pretreatment with 10 mumol/L indomethacin in both gestational diabetic and normal vessels, consistent with mediation through the formation of prostaglandins. Removal of the endothelium did not appear to alter any of the observed responses. CONCLUSIONS: Gestational diabetes produces an enhancement of the observed relaxation caused by hypoxia and the contraction produced by reoxygenation or hydrogen peroxide. PMID- 8498451 TI - Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus. AB - OBJECTIVE: Our purpose was to investigate the role of the endothelium in the human uterine arterial response to norepinephrine in the nonpregnant and pregnant states. STUDY DESIGN: Tissue was obtained from six pregnant and six nonpregnant women undergoing cesarean section or hysterectomy. Uterine radial arteries were isolated and subjected to norepinephrine dose-response curves with and without intact endothelium. RESULTS: Responses were obtained over a dose range of 10(-8) to 10(-4) norepinephrine. Initially there was no difference between vessels from pregnant and nonpregnant patients, but removal of the endothelium significantly increased the response in vessels from pregnant women. Addition of nitro-L arginine methyl ester when the endothelium was intact did not alter the dose response curves. CONCLUSIONS: In pregnancy human uterine radial arteries are more sensitive to norepinephrine than during the nonpregnant state. This increase is countered by an endothelium-derived relaxing factor. The factor is unlikely to be nitric oxide. PMID- 8498452 TI - Expression of different potassium channels in cells isolated from human myometrium and leiomyomas. AB - OBJECTIVE: Electrophysiologic characteristics of human myometrial and leiomyomatous cells isolated in culture were investigated. Both types of cell were shown to be smooth muscle cells by immunofluorescence. STUDY DESIGN: Voltage activated potassium currents were recorded by whole-cell patch-clamp techniques and analyzed for differences in expression, voltage-dependence, kinetics, and inactivation. RESULTS: Depolarizing-voltage steps from -90 mV to +30 mV elicited two types of noninactivating outward currents that differed in their kinetics in 83% (n = 36) of normal cells in culture for 3 to 5 days; 6% responded with fast (3.5 milliseconds) outward inactivating currents; 11% in culture for 1 day responded only with long-lasting inactivating currents (33.2 +/- 7.2 milliseconds). Cells isolated from leiomyomas responded preferentially (65%, n = 31) with fast (3.3 +/- 0.1 milliseconds) outward inactivating currents; 35% responded with noninactivating outward currents similar to those from normal cells. CONCLUSION: Different potassium channel currents, noninactivating and inactivating, are predominantly expressed in cells isolated from human myometrium and leiomyomas, respectively. PMID- 8498453 TI - Premenstrual symptoms and beverage consumption. PMID- 8498454 TI - Questionable category of nonmaternal death. PMID- 8498455 TI - More about low maternal serum human chorionic gonadotropin and unconjugated estriol values in triploidy. PMID- 8498456 TI - Simplified urethrocystovaginal suspension as treatment for stress urinary incontinence. PMID- 8498457 TI - The Clarke ligator. PMID- 8498458 TI - Laparoscopic radical hysterectomy with paraaortic and pelvic lymph node dissection? PMID- 8498459 TI - Longitudinal follow-up of chronic pelvic pain and occurrence of new symptoms 5 to 7 years after laparoscopy. PMID- 8498460 TI - Cervical adenocarcinoma or cervical extension. PMID- 8498461 TI - Midtrimester selective delivery of an acardiac twin. PMID- 8498462 TI - Prediction of behind-the-wheel driving performance in patients with cerebral brain damage: a discriminant function analysis. AB - Rehabilitation specialists, particularly occupational therapists, are often involved in evaluating clients' fitness to resume driving after cerebral damage due to head injury or stroke. Their available methods include separate or combined administration of predriver, simulator, and behind-the-wheel evaluations. However, use of these methods without a theoretical model on which to base test selection has yielded some criticism and little research about the effectiveness of these methods in predicting driving performance. Using the authors' Cybernetic Model of Driving as the basis for assessing abilities and behaviors relevant to driving outcome, this study sought to determine the effectiveness of the evaluation methods by discriminant analysis and measurements of sensitivity in predicting behind-the-wheel failures. Comprehensive evaluations of 106 patients revealed that residual deficits in cognition per se did not render a person unfit to drive and underscored the importance of considering behaviors in determining fitness. The methods of evaluation were shown to be relatively sensitive in predicting outcome; off-road and on-road evaluation reached sensitivities of 90% and 92% with the inclusion of behavioral measures. Formulae for predicting outcome based on methods of evaluation are provided and reasons for failures in behind-the-wheel evaluations are discussed. PMID- 8498463 TI - The effects of options on performance of an art project in adults with mental disabilities. AB - The relationships among the presence of options, interest, preference, choice, meaning, purpose, and performance in occupation are central to occupational therapy knowledge. This study examined whether giving adults with mental disabilities options at the beginning of an art occupation would motivate them to paint more than when not given options. The sample consisted of 13 men and 9 women; ages ranged from 24 to 76. The subjects were yoked in pairs. One subject from each pair was given a choice of which of five ceramic objects to paint. The second subject was instructed to paint the same type of object that the first subject had chosen. Three days to 1 week later, roles were reversed. The number of times the subject applied the paint to the object after dipping the brush into paint was recorded by the researcher. Each subject was also timed with a stopwatch from the first time paint was applied to the time the subject indicated completion of the activity. The Wilcoxon matched-pairs signed-ranks test revealed that subjects painted significantly more (Z = 2.9, p < .01) when they had a choice than when they did not have a choice. PMID- 8498464 TI - Using a sensory integrative approach to treat self-injurious behavior in an adult with profound mental retardation. AB - The treatment of self-injurious behavior in adults with mental retardation is a major challenge. A critical review of the literature compares sensory-based treatment studies by behavioral psychologists with sensory integrative treatment studies by occupational therapists. In general, therapists have used direct intervention in concentrated daily sessions. This report includes a single subject study that (a) demonstrates the clinical reasoning involved in the assessment and treatment planning process, (b) documents the efficacy of multiple short treatment sessions spread throughout the day, and (c) presents an alternative model of service provision in which direct care staff provide sensory and adaptive activities under the supervision of an occupational therapist. The use of sensory integration with adults with profound handicaps is presented as a valid application of a theory and treatment that was originally developed from work with higher functioning children with learning disabilities. PMID- 8498465 TI - The effect of life review reminiscence activities on depression and self-esteem in older adults. AB - The purpose of the study was to investigate the effect of life review reminiscence activities on reported depression and self-esteem. The study used a pretest-posttest experimental design in which 24 well older adults living in a retirement community were randomly assigned to experimental and comparison groups. The experimental group participated in six life review sessions, after which all subjects were readministered the Beck Depression Inventory and the Rosenberg Self-Esteem Survey. An analysis of covariance indicated that life review reminiscence activities did not significantly affect depression and self esteem. These findings imply that participation in life review activities did not negatively affect this sample of well older adults and that life review reminiscence is a worthwhile activity for this age group. PMID- 8498466 TI - Grip strength of children aged 3 to 7 years using a modified sphygmomanometer: comparison of typical children and children with rheumatic disorders. AB - The standard methods for testing grip strength can cause pain and inhibit accuracy of results when persons have rheumatic diseases. The first purpose of this study was to gather data on grip strength of typical children 3 to 7 years of age using the modified sphygmomanometer technique. Modified grip strength testing requires the person to squeeze an inflated sphygmomanometer (blood pressure device). Gender, age, height, weight, hand preference, and grip strength of 273 children 3 to 7 years old were recorded. Results illustrate that grip strength increases steadily from younger to older children. No differences were noted related to height, weight, or grip strength between girls and boys. The second purpose of this study was to compare the grip strength of a preliminary sample of children with rheumatic disorders to the grip strength of a sample of typical children. Results indicate that grip strength of the sample of 17 children with rheumatic disorders was significantly lower. This study offers therapists some guidance about grip strength expectations for children aged 3 to 7 years that can then be applied to a variety of special populations. PMID- 8498467 TI - Cognitive performance in senile dementia of the Alzheimer's type: the Kitchen Task Assessment. AB - The Kitchen Task Assessment (KTA) is a functional measure that records the level of cognitive support required by a person with Senile Dementia of the Alzheimer's Type (SDAT) to complete a cooking task successfully. The results allow the clinician to help caregivers understand the level of support the impaired person needs to perform daily living tasks. This paper presents the validity and internal consistency of the KTA. Data were collected from 106 persons diagnosed with SDAT. Construct validity was established by examining the relationship between subjects' performance on the KTA and standard neuropsychological measures. PMID- 8498468 TI - Hand function evaluation: a factor analysis study. AB - The purpose of this study was to investigate hand function evaluations. Factor analysis with varimax rotation was used to assess the fundamental characteristics of the items included in the Jebsen Hand Function Test and the Smith Hand Function Evaluation. The study sample consisted of 144 subjects without disabilities and 22 subjects with Colles fracture. Results suggest a four factor solution: Factor I--pinch movement; Factor II--grasp; Factor III--target accuracy; and Factor IV--activities of daily living. These categories differentiated the subjects without Colles fracture from the subjects with Colles fracture. A hand function evaluation consisting of these four factors would be useful. Such an evaluation that can be used for current clinical purposes is provided. PMID- 8498469 TI - Self-feeding system for an adult with head injury and severe ataxia. AB - This report describes a customized self-feeding system designed to increase the independence of a person with a head injury who is unable to use his arm for self feeding. The client has spastic hemiparesis in the right upper extremity and profound ataxia in the left upper extremity. Due to the severity of these disabilities, the client required total assistance at every meal since his injury 6.5 years ago. The self-feeding system described consists of an adapted spoon, a spoon holder, a scoop dish, and a dish stand. The client scoops food from the scoop dish with the adapted spoon held in his mouth and then transfers the spoon to a magnetic holder for positioning. This adaptation allows the client to position the spoon with his chin without demanding fine motor coordination. The self-feeding system is evaluated with a BAB single case research withdrawal design. Results indicate that this self-feeding system provides a viable alternative to assisting independence in self-feeding as measured by the cost benefit ratio and nutrition intake. The client used the self-feeding system for 12 months at the rehabilitation center and has continued using the equipment at his nursing home. PMID- 8498470 TI - Differences in values and goals of occupational therapy students. AB - This study compared professional values and goals of three levels of occupational therapy students: (a) seniors in baccalaureate programs (n = 337), (b) students in professional master's programs (n = 95), and (c) students in postprofessional master's programs (n = 62). Demographic characteristics including gender, age, and college background were also examined. Significant differences were identified between the baccalaureate group and the postprofessional master's group for three professional goals: (a) making a theoretical contribution to the profession, (b) performing research in the profession, and (c) educating occupational therapy students. Significant differences were also noted for four professional values. Intellectual stimulation was more often chosen by postprofessional master's students; exciting life and comfortable life were more often chosen by baccalaureate students, and helpfulness was more often chosen by the baccalaureate and postprofessional master's students. It was concluded that determining the professional values and goals of occupational therapy students may generate implications for career counseling, recruitment, increased work force, decreased attrition, and future curriculum planning. PMID- 8498471 TI - Computer applications that streamline test scoring and other procedures in occupational therapy. PMID- 8498472 TI - Psychosocial occupational therapy: time to cast off the gloom and doom. PMID- 8498473 TI - ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation. AB - Tight junctions restrict diffusion of hydrophilic solutes through the paracellular pathways of columnar epithelia. It is now apparent that the barrier function of tight junctions is physiologically regulated. Current models of the tight junction envisage junctional subunits consisting of extracellular "kisses" between plasma membranes of adjacent cells, intramembrane components represented by freeze-fracture fibrils, and cytoplasmic elements of the cytoskeleton. Insights into functional relationships between these various components of tight junctions should be provided by mapping component interrelationships in states of altered junctional permeability. Here we define the spatial distribution of ZO-1 during a state of physiological regulation of intestinal absorptive cell tight junctions. Enhanced permeation of absorptive cell junctions in response to activation of apical membrane Na(+)-solute cotransporters does not lead to redistribution of the ZO-1 pool, as judged from quantitative ultrastructural immunolocalization studies employing two different ZO-1 antibodies. Surprisingly, ZO-1, which normally localizes under junctional kisses/fibrils, focally persists at sites where junctional kisses/fibrils are cleared. These findings suggest that 1) spatial redistribution of ZO-1 does not contribute to physiological regulation of junctions elicited by activation of Na(+)-solute cotransport and 2) ZO-1 and junctional fibrils may spatially dissociate during such regulated states. PMID- 8498474 TI - Diaphragmatic fatigue assessed by 31P-magnetic resonance spectroscopy in vivo. AB - We tested whether fatigue of the piglet diaphragm is associated with inadequate oxidative metabolism as measured by magnetic resonance spectroscopy (MRS). An MRS measured ratio of inorganic phosphate to phosphocreatine (Pi/PCr) > or = 1 was taken as evidence of inadequate oxidative metabolism. Piglets (n = 10) underwent phrenic nerve pacing for 90 min with stimulation frequency of 30 Hz and duty cycle of 0.33. In a separate group of six piglets PCr, Pi, ATP, and intracellular pH were measured by in vivo MRS, and diaphragmatic blood flow was measured with radioactive microspheres at control, 2, 10, 45, 60, and 90 min of pacing. Transdiaphragmatic pressure fell from 25 +/- 3 to 15 +/- 2 mmHg (61 +/- 5%) at 2 min and remained depressed in a separate group of four piglets (P < 0.05). Conversely, compound action potential amplitude remained constant for the first 10 min of pacing and fell to 68 +/- 5% of control at 45 min (P < 0.05). Pi/PCr rose from a control value of 0.32 +/- 0.06 to 0.92 +/- 0.23 at 2 min and 0.79 +/- 0.03 at 10 min (P < 0.05) before returning toward control at 45-90 min. O2 delivery increased from 4.6 +/- 1.2 to 24.7 +/- 4.8 ml.min-1.100 g-1 at 2 min and 18.4 +/- 2.2 ml.min-1.100 g-1 at 10 min (P < 0.05) but then fell to lower levels at 45-90 min. ATP and intracellular pH remained constant except for a decline in pH to 6.98 +/- 0.09 at 45 min (P < 0.05) from the control value of 7.26 +/- 0.06.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498475 TI - Modulation of rabbit aortic Ca(2+)-activated K+ channels by pinacidil, cromakalim, and glibenclamide. AB - Rabbit aortic smooth muscle microsomes were isolated and large-conductance Ca(2+) activated K+ (BK) channels incorporated into planar lipid bilayers. The selectivity sequence and relative permeability ratios for monovalent cations was K+ (1.0) > Rb+ (0.68) > NH4+ (0.14) >> Na+, Cs+ (< 0.05). Application of pinacidil or cromakalim (0.05-10 microM) shifted the probability of opening (Po) voltage relationship in the hyperpolarizing direction. The concentrations of pinacidil and cromakalim required to increase Po 50% of the maximum value at -40 mV were 0.96 +/- 0.04 and 0.52 +/- 0.03 microM, respectively. Neither pinacidil nor cromakalim altered the voltage sensitivity of the channel (11-13 mV/e-fold change in Po). Kinetic analysis of data at -40 mV demonstrated that pinacidil (1 microM) decreased the length of time the channel dwelled in its long-closed state by 50% from 173 +/- 50 to 86 +/- 19 ms. No significant change was observed for the open time constant (20 ms). Glibenclamide (10 microM) had no effect on Po of BK channels. However, glibenclamide reversed the pinacidil- or cromakalim stimulated increase in Po of BK channels. These data suggest that both cromakalim and pinacidil increased the probability of opening of single rabbit aortic large conductance Ca(2+)-activated K+ channels and that this channel modulation may contribute to the vasorelaxant properties of these drugs. PMID- 8498476 TI - Artifactual expression of maxi-K+ channels in basolateral membrane of gallbladder epithelial cells. AB - To patch clamp the basolateral cell membrane, sheets of Necturus gallbladder epithelium were stripped of the subepithelial tissue layers and affixed apical side down on cover slips coated with Cell-Tak [F. Wehner, L. Garretson, K. Dawson, Y. Segal, and L. Reuss. Am. J. Physiol. 258 (Cell Physiol. 27): C1159 C1164, 1990]. In 90% of the patches we observed K+ channels identical to the maxi K+ channels previously demonstrated in the apical membrane (Y. Segal and L. Reuss. J. Gen. Physiol. 95: 791-818, 1990). To ascertain whether these channels were present in the native tissue, we carried out intracellular-microelectrode studies. We tested for activation of basolateral membrane K+ conductance by depolarization or by elevation of intracellular Ca2+ and for tetraethylammonium sensitivity of the basolateral membrane voltage and fractional resistance. The results were negative, indicating that maxi-K+ channels are not expressed in the basolateral membrane of the "intact" epithelium. Using the same intracellular microelectrode protocol on the apical membrane, we demonstrated the presence of an apical K+ conductance attributable to maxi-K+ channels. Additional experiments revealed a Ba(2+)-sensitive basolateral K+ conductance in the native epithelium. We conclude that in the stripped preparation there is artifactual expression of maxi-K+ channels. In addition, the native basolateral membrane K+ channels either are not expressed in this preparation or have a low conductance and cannot be discerned from the background noise. PMID- 8498477 TI - Role of calcium in organic osmolyte efflux when MDCK cells are shifted from hypertonic to isotonic medium. AB - Madin-Darby canine kidney (MDCK) cells accumulate the nonperturbing osmolytes myo inositol and betaine when grown in hypertonic medium. When returned to isotonic conditions, there is a transient basolateral efflux of these osmolytes, contributing to regulatory volume decrease. Using fura-2 fluorescence, we estimated intracellular calcium concentrations after switching MDCK cells from 500 to 300 mosM medium. Cell calcium increased 565 +/- 93 nM within 5 min. Lowering extracellular calcium inhibited the increase in cell calcium and osmolyte efflux when cells were shifted from 500 to 300 mosM medium. The calcium channel blockers lanthanum and nifedipine also inhibited osmolyte efflux after the shift from 500 to 300 mosM. In the absence of change in medium tonicity, increasing cell calcium by exposure to 1 microM ionomycin did not alter osmolyte efflux. As in PAP-HT25 cells, the cytochrome P-450 inhibitors ketoconazole and SKF-525A inhibited the efflux of both osmolytes caused by a reduction in osmolarity. Thus an early rise in cell calcium that is dependent on extra cellular calcium and a pathway blocked by inhibitors of cytochrome P-450 oxidase are critical in regulation of osmolyte efflux when MDCK cells are shifted from hypertonic to isotonic medium. PMID- 8498478 TI - ATP depletion induces an increase in the assembly of a labile pool of polymerized actin in endothelial cells. AB - Depletion of cellular ATP is associated with profound effects on the cytoskeleton, particularly disruption of microfilaments. We examined this process in bovine pulmonary artery endothelial cells by inducing differential reductions of cellular ATP using mitochondrial inhibition and variable amounts of glucose. Reduction of cellular ATP to levels < 40% of control produced discrete stages in the visible disruption of microfilaments. Using the deoxyribonuclease I assay, a reversible 11% decrease in monomeric (G) actin occurred in conjunction with microfilament disruption. Polyacrylamide gel electrophoretic (PAGE) analysis of the detergent-insoluble cytoskeleton did not reveal any differences in actin content between normal or ATP-depleted cells. Image analysis of adherent endothelial cells that had been fixed and stained with N-(7-nitrobenz-2-oxa-1,3 diazol-4-yl)-phallacidin revealed that an increase of F-actin of approximately 20% occurred in cells depleted of ATP. If the cells were lysed with detergent before fixation, the increase in F-actin was lost. PAGE analysis and electron microscopy of detergent-soluble material from the cells obtained by ultracentrifugation directly demonstrated the presence of a labile pool of F actin within the cells, which increased with ATP loss. These observations suggest that ATP may play an important role in the organization and remodeling of microfilaments within cells. PMID- 8498479 TI - Chronic exercise alters contractility and morphology of isolated rat cardiac myocytes. AB - Chronic exercise training elicits positive adaptations in cardiac contractile function and ventricular dimension. The potential contribution of single myocyte morphological and functional adaptations to these global responses to training was determined in this study. Left ventricular cardiac myocytes were isolated from the hearts of sedentary control (Sed) or exercise-trained (TR) rats. Training elicited an approximately 5% increase in resting myocyte length (Sed, 121.0 +/- 2.0 vs. TR, 126.7 +/- 2.0 microns; P < 0.05), whereas resting sarcomere length and midpoint cell width were unaffected. These data suggest that longitudinal myocyte growth contributes to the training-induced increase in end diastolic dimension. Single myocytes (28 degrees C) were stimulated at 0.067 and 0.2 Hz and shortening dynamics assessed at extracellular Ca2+ concentrations ([Ca2+]o) of 0.6, 1.1, and 2.0 mM. In both groups, maximal extent of myocyte shortening (ESmax) increased as [Ca2+]o increased and decreased as contraction frequency increased. TR myocytes were more strongly influenced by the effects of [Ca2+]o and frequency. At 0.067 Hz and 2.0 mM, ESmax was greater in TR than in Sed myocytes. The magnitude of this difference decreased as [Ca2+]o was reduced. At 0.2 Hz, ESmax was similar in Sed and TR myocytes at 2.0 mM [Ca2+]o. As [Ca2+]o was reduced, ESmax decreased more rapidly in TR than in Sed myocytes; at 0.6 mM, ESmax was greater in Sed than in TR myocytes. Our data indicate that chronic exercise influences cardiac contractile function at the single myocyte level. This study also provides evidence in support of the hypothesis that chronic exercise influences myocyte Ca2+ influx and efflux pathways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498480 TI - ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. AB - We explored the possibility that ATP-sensitive potassium (KATP) channels exist in urinary bladder smooth muscle, since synthetic openers (e.g., lemakalim) of KATP channels in other tissues relax bladder smooth muscle. Unitary currents through single potassium channels and whole cell potassium currents were measured in smooth muscle cells isolated from the detrusor muscle of the guinea pig bladder. Lemakalim (10 microM) increased whole cell K+ currents by 50 pA at -80 mV with 60 mM external K+ when the cells were dialyzed with 0.1 mM ATP and 140 mM K+. Glibenclamide (10 microM), a sulfonylurea blocker of KATP channels in other tissues, inhibited the entire lemakalim-stimulated current as well as 19 pA of the steady-state K+ current. Glibenclamide-sensitive K+ currents were not dependent on voltage. Increasing intracellular ATP from 0.1 to 3.0 mM reduced the glibenclamide-sensitive K+ current in both the presence and absence of lemakalim by about fourfold. External barium (100 microM) which blocks KATP channels in skeletal muscle reduced KATP channel currents in bladder smooth muscle by 50% at 80 mV. Lemakalim (10 microM) increased the open-state probability of single K+ channels in outside-out patches (with 0.1 mM internal ATP) by sixfold. The single channel conductance was approximately 7 pS at 0 mV with a physiological K+ gradient. This single-channel conductance was in accord with estimates of conductance made from noise analysis of the lemakalim-induced whole cell current. Glibenclamide inhibited these channels. The number of channels per cell was estimated to be approximately 425. We conclude that urinary bladder smooth muscle has KATP channels and that these channels can be opened by the K+ channel opening drug, lemakalim, and blocked by external glibenclamide and barium. We propose that modulation of these channels may regulate bladder contractility. PMID- 8498481 TI - Mechanisms of regulatory volume decrease in UC-11MG human astrocytoma cells. AB - Swelling of astrocytes commonly occurs after cerebral ischemia and other brain injuries. Because these cells constitute 20-25% of human brain volume, their swelling is a major factor in the morbidity and mortality associated with cerebral edema. Many cells, including astrocytes, resist or reverse the tendency to swell by activating transport pathways that lead to a regulatory volume decrease. Here we report the results of studies designed to elucidate the mechanisms of the regulatory volume decrease that occurs after astrocytes are swollen by exposure to hypotonic medium. Using UC-11MG cells, a well characterized, human, astrocytoma-derived line, we observed an increase in membrane permeability to both K+ and Cl- during regulatory volume decrease, consistent with a net loss of these ions. Neither the increase in K+ exit nor the regulatory volume decrease was affected by bumetanide, an inhibitor of anion cation cotransport. On the other hand, the increased K+ efflux, as well as the regulatory volume decrease, was blocked by Gd3+, suggesting a putative role of stretch-activated cationic channels in the process of volume regulation. Although increases in intracellular free Ca2+ were also observed during hypotonic treatment, they occurred well after the onset of the regulatory volume decrease. Furthermore, the regulatory volume decrease was not affected by blocking the intracellular free Ca2+ increase with dimethyl 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid or by removal of extracellular Ca2+. These results indicate that the regulatory volume decrease in UC-11MG cells may involve stretch activated channels that operate independently of changes in intracellular free Ca2+. PMID- 8498482 TI - Sulfate concentrations and transport in human bronchial epithelial cells. AB - Inorganic sulfate concentrations in the cytoplasm of human bronchial epithelial cells exceeded levels in the bathing medium under all circumstances tested. Cell sulfate concentrations were directly related to medium sulfate concentrations and inversely related to medium chloride concentrations. In physiological media there was a sulfate compartment of approximately 0.3 mM that exchanged very slowly with extracellular sulfate. In media lacking chloride, sulfate was accumulated by the cells to a level as high as 2 mM. Sulfate uptake was markedly inhibited by external chloride and by stilbene sulfonic acid derivatives but was not affected by sodium in the medium. Efflux of 35SO4(2-) was stimulated by both chloride and sulfate in the bathing medium but inhibited by stilbenes. The following compounds had no effect on sulfate movements: phorbol esters, adenosine 3',5'-cyclic monophosphate derivatives, and okadaic acid. Changes in medium tonicity were likewise without effect. Our results suggest that human bronchial epithelial cells maintain a steady-state disequilibrium for inorganic sulfate. Furthermore, sulfate appears to exist in at least two compartments in the cells: one that is slowly exchangeable with sulfate in the medium and another exchangeable compartment that is of negligible size in physiological media but that becomes very large in media lacking chloride. Sulfate is transported by an anion exchanger of broad specificity that is not influenced by substances known to modulate chloride channels. PMID- 8498483 TI - Effect of volume changes on a potassium current in rabbit corneal epithelial cells. AB - Patch-clamp recordings from rabbit corneal epithelial cells have identified a large-conductance (167 pS in symmetrical 150 mM KCl) K channel that is the major contributor to the whole cell current (J. L. Rae and G. Farrugia. J. Membr. Biol. 129: 81-87, 1992). We report here on the regulation of this channel by changes in cellular osmolality and/or volume. Exchanging the bath solution with a hyposmotic (225 or 150 mosM) solution resulted in cellular swelling and selective activation of the K current (126 +/- 86 and 273 +/- 184% increase, respectively). Hyperosmotic solution changes (380 mosM) resulted in cell shrinkage and deactivation of the K current (44.2 +/- 21% decrease). Similar increases in the cell volume and whole cell current were observed on increasing (in perforated patch experiments) the chloride ion concentration (50 mM) in the pipette intracellular solution (127 +/- 63% increase). These changes were accompanied by marked shifts in the resting membrane voltage. We conclude that the K channels in these cells can respond to alteration in cellular osmolality or volume, resulting in changes in the whole cell current and resting voltage. PMID- 8498484 TI - Purine nucleoside formation in rat skeletal muscle fiber types. AB - To determine the capacity for purine nucleotide degradation among skeletal muscle fiber types, we established energy-depleted conditions in muscles of the rat hindlimb by inducing muscle contraction during ischemia. After 5, 10, 15, or 20 min of ischemic contractions, representative muscle sections were freeze-clamped and analyzed for purine nucleotides, nucleosides, and bases. Fast-twitch muscle sections accumulated about fourfold more IMP than the slow-twitch red soleus muscle. Inosine begins to accumulate at < 0.5 mumol/g IMP in slow-twitch muscle and at approximately 2 mumol/g IMP in fast-twitch muscle. This suggests that inosine is formed intracellularly by 5'-nucleotidase acting on IMP and that the activity and/or substrate affinity of the 5'-nucleotidase present in slow-twitch muscle may be higher than in fast-twitch muscle. At similar concentrations of precursor IMP, slow-twitch muscle has a greater capacity for purine nucleoside formation and should be more dependent on salvage and de novo synthesis of purine for the maintenance of muscle adenine nucleotides. Fast-twitch muscles are better able to retain IMP for subsequent reamination due to their lower capacity to degrade IMP to inosine. PMID- 8498485 TI - Mg2+ buffering in cultured chick ventricular myocytes: quantitation and modulation by Ca2+. AB - To characterize the Mg2+ buffering of cultured chick ventricular myocytes, cytosolic Mg2+ was increased by liberating Mg2+ normally chelated by ATP upon total depletion of ATP content. Because the total Mg content and cell volume remained constant during this time, the difference between the amount of Mg2+ liberated (2.7 mM) and the 0.9 mM increase in cytosolic Mg2+ activity measured fluorometrically with mag-fura-2 indicates a sizable Mg2+ buffering. A new term, the Mg2+ buffer coefficient (BMg), was derived to quantify this buffering. We also determined that cytosolic Mg2+ activity increased by only 0.6 mM in cells acutely exposed to zero external Ca2+ during ATP depletion. In the absence of extracellular Ca2+, the basal cytosolic Ca2+ activity (alpha Ca2+i) was reduced by 72%, whereas the increase in alpha Ca2+i induced by ATP depletion was substantially blunted; no difference in either the time course of adenine nucleotide changes or the Ca and Mg content was observed. The BMg value calculated for these cells indicates that Mg2+ buffering is substantially greater in the absence of extracellular Ca2+ (2.5) than when extracellular Ca2+ is present (1.4), indicating that alpha Ca2+i affects cytosolic Mg2+ activity in ventricular myocytes. Therefore the Mg2+ buffering of ventricular myocytes appears to be comprised of at least two components: 1) a Ca(2+)-insensitive adenine nucleotide pool and 2) a Ca(2+)-sensitive nonadenine nucleotide pool. PMID- 8498486 TI - Inhibition of Na-K-2Cl cotransport and bumetanide binding by ethacrynic acid, its analogues, and adducts. AB - The inhibitory effect of ethacrynic acid (EA) and a variety of its derivatives on Na-K-2Cl cotransport in avian erythrocytes was investigated. The most potent compound tested was the adduct of EA with L-cysteine, with an IC50 of 7.2 x 10( 7) M. EA itself, dihydro-EA, EA-D-cysteine, and adducts of EA with other sulfhydryl (-SH) compounds were much less potent. The mechanism of action of EA and EA-L-cysteine differed in several respects: 1) EA-L-cysteine acted more rapidly than EA (half times of < 1 and 4 min, respectively, at 37 degrees C); 2) the action of EA-L-cysteine was reversible by washing, whereas that of EA was not; and 3) the degree of inhibition by EA-L-cysteine varied with medium [K], whereas that of EA did not. The inhibitory effects of both EA-L-cysteine and EA were affected by medium [Na] and [Cl]. We conclude that EA-L-cysteine does not "deliver" EA to transport-related -SH residues or act as an alkylating agent but has some stereospecific effect on cotransport that is a property of the entire molecule. EA does appear to inhibit cotransport by alkylating -SH residues, as closely related compounds lacking the ability to covalently react with such groups were reversible, and other -SH reagents (e.g., N-ethylmaleimide) also inhibited cotransport. EA, EA-L-cysteine, and EA-D-cysteine all inhibited [3H]bumetanide binding to membranes from activated avian erythrocytes at concentrations similar to those that inhibited cotransport. It is possible that the EA and bumetanide types of diuretics interact with closely apposed sites on the Na-K-2Cl cotransporter. PMID- 8498487 TI - Electrogenic Na+ absorption of rat distal colon is confined to surface epithelium: a voltage-scanning study. AB - There is no quantitative assignment of large intestinal electrogenic Na+ absorption to surface epithelium and crypts so far. We determined the spatial distribution of electrogenic Na+ absorption to crypts and surface epithelium of rat late distal colon using a modified voltage-scanning technique. Voltage deflections resulting from external 30-Hz current were sensed by an extracellular microelectrode stepping at 0.7 Hz above crypt openings or surface epithelium. Local conductances were calculated applying a planar model of electrical field distribution to surface epithelium and a electrostatic disk source model to the crypts. These models were confirmed by methodological experiments where the electrode position was varied in vertical and horizontal direction. Electrogenic Na+ absorption was detected by blocking apical Na+ channels by mucosal 0.1 mM amiloride. Under control conditions surface epithelium contributed 44% (2.0 +/- 0.2 mS/cm2) and crypts 56% (2.6 +/- 0.2 mS/cm2) to the total conductance of 4.6 +/- 0.4 mS/cm2. Electrogenic Na+ absorption was induced by 6 h in vitro incubation in a medium containing 3 nM aldosterone. This caused a short-circuit current (ISC) of 12.1 +/- 0.8 mumol.h-1.cm-2, which was paralleled by a 2.5-fold increase in surface epithelial conductance to 5.1 +/- 0.4 mS/cm2, whereas crypt conductance was not significantly altered (3.0 +/- 0.2 mS/cm2). Amiloride reversed ISC to -0.8 +/- 0.1 mumol.-1.cm-2 and decreased surface epithelium conductance to 2.3 +/- 0.3 mS/cm2 but again had no significant effect on crypt conductance (2.5 +/- 0.3 mS/cm2). Sham incubation (no hormones added) for 6 h neither induced electrogenic transport nor altered local epithelial conductances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498488 TI - Role of Na-K-Cl cotransport in vascular endothelial cell volume regulation. AB - Vascular endothelial cells have been shown previously to possess a highly active Na-K-Cl cotransport system that mediates the major portion of total K influx and is regulated by a variety of vasoactive hormones and neurotransmitters. These observations suggest that the cotransporter may be an important component of endothelial cell function. The present study was conducted to investigate the role of Na-K-Cl cotransport in regulation of endothelial cell volume. Cultured bovine aortic endothelial cells were exposed to media of varying tonicities and Na-K-Cl cotransport activity assessed as bumetanide-sensitive K influx. Increasing the extracellular tonicity by increments as small as 10 mosM was found to cause significant stimulation of cotransport activity, and lowering tonicity reduced activity of the transporter. Exposure of endothelial cells to hypertonic medium was also found to increase bumetanide-sensitive net uptake of Na and K and total cellular Na and K content. Endothelial cell volume was evaluated by [14C]urea determination of intracellular water space in endothelial monolayers and by electronic cell sizing of suspended cells. Treatment of the cells with agents that stimulate Na-K-Cl cotransport activity was found to increase cell volume, whereas cotransport-inhibiting agents decreased cell volume. Exposure of the cells to hypertonic medium caused a rapid decrease in cell volume, followed by a regulatory volume increase that was greatly attenuated by bumetanide. The volume recovery was partially inhibited by the Na-H exchange inhibitor amiloride and was nearly abolished by bumetanide and amiloride in combination. Endothelial cells of pulmonary artery and cerebral microvessels were also found to exhibit increased Na-K-Cl cotransport activity on exposure to hypertonic media. These findings suggest that Na-K-Cl cotransport is of major importance in endothelial cell volume regulation. PMID- 8498489 TI - G protein coupling of human platelet V1 vascular vasopressin receptors. AB - We used several approaches to identify the G protein coupled to V1 vascular arginine vasopressin (AVP) receptors of human platelets. In purified platelet membranes, high-affinity specific binding of [3H]AVP but not that of the V1 vascular antagonist [3H]d(CH2)5Tyr(Me)AVP was modulated by guanosine 5'-O-(3 thiotriphosphate) or sodium fluoride both in the presence and absence of MgCl2. AVP failed to modify the [alpha-32P]GTP labeling pattern or the cytosolic translocation of the 24- to 27-kDa GTP-binding proteins. AVP-stimulated GTPase activity of platelet membranes was blocked by antibodies specific for the COOH terminal of the Gq alpha protein. AVP increased labeling of a 42-kDa platelet membrane protein by the photoreactive GTP analogue [alpha-32P]azidoanilido GTP. Immunoblotting of platelet proteins with various G protein-specific antibodies revealed that the 42-kDa protein labeled with [alpha-32P]azidoanilido GTP was immunoblotted only by antibodies specific for the alpha-subunit of GQ-11. Thus V1 vascular AVP receptors of human platelets are coupled in a divalent cation dependent manner to a G protein belonging to the Gq-11 family. PMID- 8498490 TI - Effects of exercise and weight loss on leucine turnover in different types of obesity. AB - These studies were performed to determine whether protein turnover during exercise and after weight loss is influenced by obesity and body fat distribution. Leucine carbon flux was measured before, during, and after 2.5 h of bicycle exercise in 10 upper body obese, 9 lower body obese, and 6 nonobese, age matched, premenopausal women. The obese women then followed an energy-restricted diet for 16 wk, resulting in approximately 8 kg weight loss. Baseline leucine carbon flux was greater (P < 0.01) in obese women than in nonobese women but decreased in a similar fashion in response to exercise in all groups. There were no differences between upper body and lower body obese women during exercise. After weight loss, baseline leucine carbon flux decreased (P < 0.05) similarly in both groups of obese women and was further suppressed by exercise. Thus obesity phenotype has no specific effect on either baseline protein turnover or the antiproteolytic response to moderate intensity exercise or weight loss. We conclude that the previously observed defect in insulin suppression of leucine flux in upper body obese women appears related to insulin resistance and does not represent an inherent abnormality of protein metabolism. PMID- 8498491 TI - Myofibrillar protein synthesis in young and old men. AB - We tested the hypothesis that healthy older men (> 60 yr old) have a slower rate of myofibrillar protein synthesis than young men (< 35 yr old). Myofibrillar protein synthesis was determined by the in vivo incorporation of L-[1-13C]leucine into myofibrillar proteins obtained by muscle biopsy. Subjects were eight young (21-31 yr) and eight older (62-81 yr) men, all healthy and moderately active. There was no significant difference in the mean height and weight of the two age groups, but the older group had 12% less lean body mass (determined by 40K counting) and 21% less muscle mass (estimated by urinary creatinine excretion). Upper leg strength was approximately one-third lower in the older subjects according to isokinetic dynamometry. The fractional rate of myofibrillar protein synthesis was 28% slower in the older group (0.039 +/- 0.009 vs. 0.054 +/- 0.010 %/h, mean +/- SD, P < 0.01). Total myofibrillar protein synthesis, estimated as total myofibrillar mass (from creatinine excretion) times the fractional synthesis rate, was 44% slower in the older group (1.4 vs. 2.5 g/h, P < 0.001). Whole body protein synthesis, assessed as the difference between leucine disappearance rate and leucine oxidation, was marginally slower (8%, P = 0.10) in the older group, but not when the data were adjusted for lean body mass. Myofibrillar protein synthesis was a smaller fraction of whole body protein synthesis in the older group (12 vs. 19%). Reduced myofibrillar protein synthesis may be an important mechanism of the muscle atrophy associated with aging. PMID- 8498492 TI - Endogenous neuropeptide Y regulates thyroid blood flow. AB - Neuropeptide Y (NPY) is present in thyroid sympathetic nerve fibers. To assess the involvement of endogenous NPY in the regulation of thyroid function, a NPY antiserum was produced in a rabbit, characterized, and used for immunization of normal and hyperthyroid rats. Plasma thyroxine, thyroid-stimulating hormone (TSH), thyroidal, and other organ blood flows (BF) were measured in anesthetized (ketamine and pentobarbital sodium) male Sprague-Dawley rats at 1 h after intravenous administration of 1 ml of the antiserum, normal rabbit serum, or saline. Immunization against NPY had no effect on the plasma levels of thyroxine, TSH, or arterial blood pressure, but it significantly increased thyroidal BF in normal rats. In the hyperthyroid rats (treated with 5 micrograms.100 g body wt .day-1 thyroxine for 6 days), the NPY antiserum reversed the hyperthyroidism induced decrease in thyroid BF and significantly increased duodenal and testicular BF values, but it did not alter BF values in four other organs. These results indicate that endogenous NPY regulates thyroid BF in normal rats. They also provide an example of NPY involvement in the pathophysiological adjustment of some organs to hyperthyroidism. PMID- 8498493 TI - Skeletal unloading decreases production of 1,25-dihydroxyvitamin D. AB - The plasma concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] decreases during skeletal unloading and increases when normal weight bearing is restored. To determine whether these changes in plasma 1,25(OH)2D reflect changes in production, metabolic clearance, or both we measured the kinetics of 1,25(OH)2D metabolism in rats whose skeletons were normally loaded, unloaded, or reloaded after a period of nonweight bearing. Skeletal unloading produced a transient but striking fall in the production (-73%) and plasma concentration (-72%) of 1,25(OH)2D without having a significant effect (< 20%) on metabolic clearance. Skeletal reloading returned production to normal. Bone formation predictably decreased during unloading and returned to normal after return to weight bearing. No consistent changes in blood ionized calcium, plasma immunoreactive parathyroid hormone (irPTH), or plasma phosphorus occurred. These data suggest that the changes in plasma 1,25-(OH)2D associated with changes in skeletal weight bearing primarily reflect changes in 1,25(OH)2D production. The data provide no evidence that the changes in 1,25(OH)2D production are a consequence of changes in blood ionized calcium, plasma irPTH, or phosphorus. PMID- 8498494 TI - Radioactively iodinated cyclo(His-Pro) crosses the blood-brain barrier and reverses ethanol-induced narcosis. AB - Cyclo(His-Pro) (cHP) is a peptide widely distributed in the central nervous system (CNS) and peripheral tissues that can affect brain function after either peripheral or CNS administration. This suggests that cHP may be a neuromodulator capable of crossing the blood-brain barrier (BBB). We, therefore, studied the ability of radioactively labeled cHP (I-cHP) to cross the BBB. We found that I cHP can cross the BBB in either the direction of blood to brain or brain to blood by nonsaturable mechanisms. The rate of entry of I-cHP into the CNS was low in comparison with other peptides, especially considering its relatively low molecular weight and high lipid solubility. However, this slow entry was offset by a long half-life in blood and extreme enzymatic resistance, allowing cHP to accumulate in the CNS. This accumulation was sufficient to allow intravenous cHP to reverse ethanol-induced narcosis, an effect mediated through the CNS. The rate of entry of I-cHP was resistant to conditions that alter the passage of some other substances across the BBB or that have been shown to affect cHP metabolism such as aging, diabetes, and pretreatment with aluminum. Entry of cHP into the brain was not retarded by binding to serum proteins. Significant amounts of I-cHP entered the serum, brain, and other tissues after intraperitoneal administration, the route used in many studies of cHP. Taken together, these results show that cHP is a highly stable peptide that, after intravenous injection, slowly enters the brain by a nonsaturable mechanism in amounts large enough to affect such aspects of the CNS as ethanol-induced narcosis. PMID- 8498495 TI - Effect of sodium intake on insulin sensitivity. AB - To examine the effects of sodium intake on insulin sensitivity, we performed euglycemic insulin clamp studies (40 mU.m-2.min-1) in eight healthy normotensive nondiabetic white males (age = 36 +/- 5 yr; wt = 66 +/- 3 kg) after 5 days on high (200 meq/day)- and low (10 meq/day)-sodium diets administered in random order. High sodium intake was associated with significantly greater urinary sodium excretion (160 +/- 7 vs. 8 +/- 2 meq/day; P < 0.0001), suppression of plasma aldosterone (7 +/- 3 vs. 38 +/- 6 ng/dl; P < 0.001) and renin (1.5 +/- 0.2 vs. 6.0 +/- 0.9 ng.ml-1.h-1; P < 0.005) levels, but no change in blood pressure (116 +/- 3/63 +/- 2 vs. 114 +/- 3/64 +/- 2 mmHg; P = not significant). The rate of glucose infusion during the clamp was significantly reduced during the high- vs. low-sodium diet (279 +/- 19 vs. 334 +/- 24 mg.m-2.min-1; P < 0.01). This impairment in insulin sensitivity was not related to changes in serum potassium, epinephrine, norepinephrine, cortisol, or growth hormone but was highly correlated with an increment in circulating free fatty acid levels during high sodium intake (r = 0.82, P < 0.05). These data suggest that 1) high sodium intake may exacerbate insulin resistance by increasing circulating free fatty acids, and 2) differences in sodium intake may influence measures of insulin sensitivity in other disease states. PMID- 8498496 TI - Effects of hyperinsulinemia on the subsequent hormonal response to hypoglycemia in conscious dogs. AB - The aim of this study was to determine if differing periods of prior hyperinsulinemic nonhypoglycemia can modify the subsequent counterregulatory response to hypoglycemia. Experiments were carried out on 19 normal 18-h fasted conscious dogs. Insulin was infused intraportally at 8 mU.kg-1.min-1 for 3 h on two occasions and 3.5 h on a third separate occasion. This resulted in similar steady-state arterial insulin levels during each protocol (4,370 +/- 433 pmol/l). Each animal was maintained at a similar plasma glucose nadir (2.8 +/- 0.6 mmol/l) for 2 or 2.5h, depending on the protocol. In protocol I (n = 7) plasma glucose was allowed to fall to the desired hypoglycemic plateau by 30 min. In a second group of dogs (protocol II, n = 5) there was a 30-min period of euglycemic hyperinsulinemia followed by a 30-min fall (similar to protocol I) in plasma glucose. In a third group of dogs (protocol III, n = 7), there was an initial 15 min period of euglycemic hyperinsulinemia followed by a 45-min fall in plasma glucose. Differing periods of euglycemic hyperinsulinemia had distinct effects on subsequent counterregulation. During the final 2 h of hypoglycemia the incremental area under the curve (AUC) for glucagon was significantly greater in protocol I vs. II (3.0 +/- 1.0, -0.5 +/- 0.2 micrograms.l-1.min-1, P < 0.02, respectively). Conversely, catecholamine levels were increased in protocol II (30 min prior hyperinsulinemic euglycemia) compared with protocol I (epinephrine 1,448 +/- 268, 855 +/- 119 nmol.l-1.min-1; norepinephrine 244 +/- 30, 166 +/- 23 nmol.l-1.min-1, respectively, P < 0.05). During protocol III, glucagon and catecholamine levels were intermediate between protocols I (no euglycemic hyperinsulinemia) and II (30 min euglycemic hyperinsulinemia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498497 TI - Insulin resistance is localized to skeletal but not heart muscle in type 1 diabetes. AB - To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle 1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498498 TI - Zinc metabolism and metallothionein expression in bone marrow during erythropoiesis. AB - Zinc metabolism and metallothionein induction in rat bone marrow were investigated during induced erythropoiesis. Redistribution of body zinc was measured with 65Zn after acute blood loss in rats fed zinc-restricted or zinc adequate diets. Uptake of 65Zn by bone marrow was related to time after blood loss, metallothionein induction, and dietary zinc status. Increased 65Zn uptake by marrow of zinc-restricted rats suggests a minimal amount of zinc is necessary to support expansion of the erythrocytic compartment. Zinc induction of marrow metallothionein also occurred in rats in which anemia was produced using phenylhydrazine. Anemic rats which were administered zinc had higher concentrations of marrow metallothionein compared with control rats. Induction of marrow metallothionein by zinc in nonanemic rats required prior treatment with erythropoietin. Percoll fractionation showed marrow metallothionein was most abundant in erythroblasts. These experiments suggest metallothionein synthesis occurs in erythropoietin-sensitive precursor cells in the marrow in response to increased zinc accessibility. PMID- 8498499 TI - FSH secretory pattern and degree of concordance with LH in amenorrheic, fertile, and postmenopausal women. AB - Pulsatile secretion of gonadotropin was investigated in amenorrheic patients and in fertile and postmenopausal women to assess both follicle-stimulating hormone (FSH) episodic secretion and its temporal coupling with luteinizing hormone (LH). Three groups of amenorrheic patients were studied: hyperandrogenic (n = 20), hypogonadotropic (n = 51), and normogonadotropic (n = 31). Nineteen fertile women (during the follicular and luteal phases of the cycle) and sixteen postmenopausal women were investigated as reference groups. All subjects demonstrated the presence of a distinct pulsatile pattern with LH and FSH pulses/4 h as follows: hyperandrogenic 3.95 +/- 0.26 and 3.85 +/- 0.2, hypogonadotropic 3.76 +/- 0.26 and 3.9 +/- 0.16, normogonadotropic 3.5 +/- 0.2 and 3.9 +/- 0.17 LH and FSH pulses/4 h, respectively (means +/- SE). Normal controls showed 4.1 +/- 0.2 and 3.1 +/- 0.2 pulses/4 h for LH (P < 0.05) and 3.2 +/- 0.1 and 3.6 +/- 0.3 pulses/4 h for FSH, during follicular and luteal phases, respectively. Postmenopausal women showed 3.6 +/- 0.2 and 3.0 +/- 0.3 pulses/4 h for LH and FSH, respectively. Specific concordance (SC) index demonstrated that LH and FSH were significantly and simultaneously secreted in all groups. Conversely, LH and FSH were not temporally related during the luteal phase. In conclusion, we report a distinct FSH episodic secretion and its temporal linkage with LH pulses irrespective of plasma concentrations of gonadal steroids in secondary amenorrhea. PMID- 8498500 TI - Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells. AB - The effects of skeletal unloading on osteoblastic cells were evaluated in tail suspended rats. Hindlimb elevation for 14 days induced osteopenia, decreased histomorphometric indexes of bone formation in tibial metaphysis, and reduced plasma osteocalcin and alkaline phosphatase (ALP) levels compared with controls. The in vitro proliferation of osteoblastic cells isolated from the endosteal bone surface of suspended tibias was decreased by 42 and 31% at 2 and 4 days of culture, respectively, compared with controls, as shown by [3H]thymidine labeling and cell number. The proliferation of ALP-positive marrow stromal cells was also decreased by 20-24% at 1 and 2 days of culture. However, ALP activity in bone derived cells and marrow stromal cells was not different in unloaded and control rats, and the number of bone cells synthesizing osteocalcin, osteonectin, and type I or type III collagen was identical in the two groups. The results indicate that the inhibition of bone formation induced by skeletal unloading is related to a decreased proliferation of putative osteoblast precursor cells present along the endosteal bone surface and in the marrow stroma. PMID- 8498501 TI - Impaired epidermal growth factor production in genetically obese ob/ob mice. AB - Epidermal growth factor (EGF) is a potent inhibitor of adipose differentiation in vitro and delays adipose tissue development in vivo. Here we show that in the homozygous male obese mice the level of EGF in the submaxillary gland and plasma is significantly lower than in the glands and plasma of age-matched control littermates. This EGF deficiency in ob/ob mice was observed as early as 5 wk of age when obesity had just become apparent and was also found in adult mice. The level of prepro-EGF mRNA expression in the submaxillary gland was also lower in obese mice than in control littermates. However, the level of kidney prepro-EGF mRNA was the same in mice with both phenotypes, suggesting that the regulation of prepro-EGF mRNA expression is different in both tissues. These results indicate that genetic obesity in mice is accompanied by a decrease in the production of EGF. PMID- 8498502 TI - Triiodothyronine receptor complex in developing rat brain and pituitary. AB - In vitro saturation analysis combined with nuclear 3,5,3'-triiodothyronine (T3) quantification was used to examine the changes in T3 binding parameters in rat pituitary and cerebrocortical nuclei from fetal day 14 to postnatal day 20. T3 receptors were first detectable in neuronal, glial, and pituitary nuclei on fetal days 14, 17, and 18, respectively. Thereafter T3 receptor concentrations in neuronal, glial, and pituitary nuclei increased throughout the developmental period studied, reaching maximal levels during neonatal life (1,129, 1,025, and 635 fmol/mg DNA, respectively). T3 levels in pituitary, neuronal, and glial nuclei also increased during development there being a 35-, 34-, and 120-fold rise between fetal days 16-18 and the 20th postnatal day. Endogenous T3 receptor occupancy throughout the experimental period increased six- to ninefold in the three types of nuclei. The presence of T3 receptor complex in the pituitary and cerebrocortical nuclei during perinatal development lends further support to the hypothesis that T3 may be an important factor in determining the differentiation and development of these cells. PMID- 8498503 TI - Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats. AB - This work reports the roles of the concentration of lactate and of fatty acids on lactate uptake by liver cells isolated from fed or 24-h starved rats. Hepatocytes isolated from fed rats released lactate and pyruvate. The addition of lactate shifted the lactate balance from net release to net utilization, with a threshold at approximately 2 mM. Lactate favored its own utilization by 1) increasing the lactate-to-pyruvate ratio (L/P) and 2) inhibiting hepatic glycolysis. The addition of oleate to the cells elicited 1) a net reduction of the release of lactate and pyruvate in basal conditions, 2) a marked decrease in the threshold of lactate utilization, down to values close to 0.5 mM, and 3) an important stimulation of the utilization of lactate, at physiological concentrations of 2-3 mM. These changes in lactate utilization induced by oleate were accompanied by a parallel increase of the L/P. Oleate acted by decreasing the cellular concentrations of pyruvate. Such an effect was mediated by 1) an inhibition of glycolysis and 2) a rise in pyruvate utilization toward glucose. Moreover, it seems that the capacity of various fatty acids to stimulate lactate utilization depends on their rate of oxidation by the liver. In liver cells isolated from 24 h starved rats, in keeping with the activation of gluconeogenesis, lactate was utilized by hepatocytes even at low concentrations. Because of the low glycolysis and of the high utilization of pyruvate in these cells, the presence of oleate only induced a moderate increase of lactate utilization (+32%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498504 TI - Effect of spaceflight on human protein metabolism. AB - Nitrogen balance and the whole body protein synthesis rate were measured before, during, and after a 9.5-day spaceflight mission on the space shuttle Columbia. Protein synthesis was measured by the single-pulse [15N]glycine method. Determinations were made 56, 26, and 18 days preflight, on flight days 2 and 8, and on days 0, 6, 14, and 45 postflight. We conclude that nitrogen balance was decreased during spaceflight. The decrease in nitrogen balance was greatest on the 1st day when food intake was reduced and again toward the end of the mission. An approximately 30% increase in protein synthesis above the preflight baseline was found for flight day 8 for all 6 subjects (P < 0.05), indicating that the astronauts showed a stress response to spaceflight. PMID- 8498505 TI - Hepatic glucose production during the labeled IVGTT: estimation by deconvolution with a new minimal model. AB - A method for the estimation of hepatic glucose production during a labeled intravenous glucose tolerance test (IVGTT) is proposed. Stable-label IVGTT data in normal subjects have been considered. The method is based on deconvolution and uses a new two-compartment minimal model of glucose kinetics to describe the time varying impulse response of the glucose system. A new model of glucose kinetics was needed because the available single-compartment minimal model, specifically developed to interpret labeled IVGTT data, provided a nonphysiological pattern of hepatic glucose production. The new minimal model has two novel features: glucose kinetics are described by a two-compartment structure, and insulin exerts its action on the irreversible loss of the slowly exchanging glucose pool. The deconvolution scheme used to reconstruct hepatic glucose production is described in detail both in terms of computational aspects and reliability. Confidence limits of the reconstructed hepatic glucose production in each individual are derived by taking into account both the measurement error of the data and the uncertainty associated with the description of the impulse response. Physiological plausibility of the time course of hepatic glucose production provided by this new method is discussed. The ability of the new model to reconstruct hepatic glucose production considerably enriches the kinetic portrait of glucose metabolism that can be obtained from the minimal-model analysis of labeled IVGTT data. PMID- 8498506 TI - K+ currents in rabbit esophageal muscularis mucosae. AB - Single cells were obtained from esophageal muscularis mucosae of the rabbit using enzymatic dispersion. Their electrophysiological properties were studied with both conventional whole cell and nystatin-perforated patch techniques. The latter technique was used to prevent "washout" of intracellular constituents and to maintain endogenous buffering of Ca2+. The average resting potential of these cells was -54 +/- 3.2 mV in the conventional recording and -51 +/- 4.4 mV in perforated patch recordings. In the current-clamp mode, regenerative responses were consistently observed in perforated patch recordings, but not when conventional whole cell gigaseal methods were used. Conventional whole cell voltage-clamp methods revealed outward currents on depolarization from a holding potential of -70 mV. These currents were inhibited by extracellular tetraethylammonium (TEA, 5-10 mM) and CoCl2 (4 mM), indicating that the predominant outward current is a Ca(2+)-activated K+ current. In the presence of TEA, inward Ca2+ currents were unmasked. In contrast, when the nystatin perforated patch technique was used, depolarizations resulted in a net inward current followed by an outward current. The outward current was inhibited by CoCl2 (2 mM) and TEA (5 mM) to the same extent as in conventional recordings. A second component of K+ current was observed in both types of recordings when extracellular Ca2+ influx was abolished and also in the presence of TEA. This slowly activating persistent K+ current resembled a delayed rectifier K+ current. These studies show that the rabbit tunica muscularis mucosal cells possess voltage-activated Ca2+ and K+ channels as well as the capability to elicit action potentials. PMID- 8498507 TI - Inhibition of gastric acid secretion by oxyntomodulin and its 19-37 fragment in the conscious rat. AB - Oxyntomodulin (Oxm) is a hormone, released from the intestine during digestion. Its target tissue is the gastric mucosa, where it inhibits acid secretion. It contains the 29-amino acid glucagon moiety, extended at its COOH-terminal end by an octapeptide. The glucagon moiety contains a basic doublet (Arg17-Arg18). Our working hypothesis was that the mode of action of Oxm may imply a processing of the molecule at the Arg-Arg doublet, releasing Oxm-(19-37). We compared the effect of Oxm with that of Oxm-(19-37) on gastric acid secretion in the conscious rat provided with a chronic gastric fistula. The acid secretion was plateau stimulated by a perfusion of either pentagastrin or histamine. Whereas Oxm or Oxm (19-37) had no effect on basal acid secretion, both peptides inhibited pentagastrin (0.5 micrograms.kg-1.h-1)- and histamine (0.4 mg.kg-1.h-1) stimulated acid secretion in a dose-dependent manner. When the metabolic clearance rate for each peptide was taken into account, the 19-37 fragment was as potent as the whole Oxm, regardless of the type of stimulant. When the dose of pentagastrin was increased from 0.175 to 1.1 micrograms.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) also increased. In contrast, when the dose of histamine was increased from 0.25 to 1.2 mg.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) decreased. Oxm-(19-37) (70-140 pmol/kg) displayed the same behavior as the whole molecule under both types of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498508 TI - Effect of varying the rate and pattern of gastric distension on its sensory perception and motor activity. AB - The aim of the present study was to see if varying the rate and pattern of gastric distension affected its motor and sensory responses to distension. A balloon was used to carry out distensions in male volunteers at constant rates of 20, 50, 100, and 200 ml/min. In addition rapid (75 ml/s) intermittent distensions (RID) were carried out with the use of a large hand-held syringe. Subjects were asked to indicate the first perception of the balloon, fullness, and discomfort. Increasing the rate of ramp distension caused all sensations to occur at higher volumes and higher pressures and reduced the frequency and amplitude of phasic oscillations in gastric pressure. During RID, the same sensations were experienced at much reduced volumes but were poorly sustained. These data suggest that ramp and RID are likely to induce gastric sensations by activating different populations of receptors. The responses to ramp distension are compatible with the activation of stretch receptors situated in parallel with the muscle elements, whereas RID appear to be activating a different population of rapidly adapting mechanoreceptors possibly situated in the mucosa. PMID- 8498509 TI - Attenuation of endotoxin-induced intestinal microcirculatory damage by eicosapentanoic acid. AB - The major objective of this study is to investigate whether oral administration of eicosapentanoic acid (EPA) has any preventive effect on endotoxin-induced microcirculatory damage of rat small intestine. EPA in a daily dose of 300 mg/kg was orally given to male Wistar rats for 3 wk. Submucosal microvessels of the ileum were observed by intravital microscopy equipped with a high-speed video camera system after the intra-arterial infusion of endotoxin at a dose of 2 mg.kg 1.h-1. The number of sticking leukocytes was significantly increased at 30 min after the treatment of endotoxin especially along the smaller branch of intestinal venules. It reached the maximal plateau at 45 min after treatment. The pretreatment of EPA significantly attenuated the increase in sticking leukocytes induced by endotoxin. A platelet-activating factor (PAF) antagonist 2-[N-acetyl-N (2-methoxy-3-octadecylcarbamoyloxy propoxycarbonyl) aminomethyl]-1 ethylpyridinium chloride (CV-6209) significantly prevented the increased leukocyte sticking to the same extent as EPA treatment. Thirty minutes after endotoxin infusion, red blood cell (RBC) velocity was significantly decreased in both arterioles and venules. RBC velocity appeared to be continuously decreased thereafter and reached its minimum value at approximately 60 min. EPA treatment was revealed to prevent the decrease in RBC velocity of microvessels induced by endotoxin. CV-6209 also significantly attenuated the decreased RBC velocity. The remarkable elevation of PAF content in the ileal mucosa as observed by endotoxin infusion was also significantly attenuated by administration of EPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498510 TI - Protection against hydrophobic bile salt-induced cell membrane damage by liposomes and hydrophilic bile salts. AB - Under physiological circumstances, cell membrane damage is not evident in biliary systems, despite the fact that hydrophobic bile salts are known to induce such damage by their detergent effects. The aim of this study was to determine the cytoprotective effects of liposomes and hydrophilic bile salts against hydrophobic bile salt-induced cell membrane damage, with the use of hemolysis of erythrocytes as a model of cytotoxicity. Washed human erythrocytes were incubated for 10, 30, 60, 90, and 120 min in buffered media (pH 7.45) containing increasing concentrations of different bile salts (1, 2.5, 5, 25, 50 mM). The cytotoxicity of the bile salts was found to be dose and time dependent and was correlated to the degree of the hydrophobicity of the bile salts as determined by the retention factor in reversed-phase high-performance liquid chromatography. Hydrophobic bile salt-induced hemolysis was reduced by liposomes and hydrophilic bile salts. Cytoprotection by liposomes was related to the degree of saturation of the fatty acyl chains, and cytoprotection by hydrophilic bile salts was related to their hydrophilicity. These in vitro findings indicate that vesicles may play a role in protection against cell membrane damage by hydrophobic bile salts in biliary systems and that such damage may be caused by an imbalance between hydrophobic and hydrophilic bile salts. PMID- 8498511 TI - Multiple kinases phosphorylate the pancreatic cholecystokinin receptor in an agonist-dependent manner. AB - The cholecystokinin (CCK) receptor on the rat pancreatic acinar cell is a guanine nucleotide-binding protein (G protein)-coupled receptor, which was recently demonstrated to be phosphorylated in response to agonist stimulation (Klueppelberg et al., J. Biol. Chem. 266: 17744-17746, 1991). In this work, we establish that this receptor is phosphorylated in response to a variety of homologous and heterologous secretagogues and that these phosphorylation events represent action by more than one protein kinase. One subgroup of kinases includes one or more isotype of protein kinase C (PKC), and is capable of playing a role in homologous and heterologous desensitization. A second subgroup of kinases that acts on the CCK receptor was defined by its resistance to 10 microM staurosporine, which was shown to inhibit all PKC in these cells. The activity of the second group of kinases was observed only in response to occupation of the CCK receptor by high concentrations of native hormone, raising the possibility of a "receptor-specific kinase." Similar to the prototypical kinase, beta-adrenergic receptor kinase (beta-ARK), this activity was inhibited in permeabilized cells by heparin. Furthermore, like this enzyme activity, beta-ARK was shown to be resistant to staurosporine. Based on its action on a G protein-coupled receptor, its activation at high concentrations of native agonist, and its pattern of inhibition, we believe that the staurosporine-insensitive CCK receptor kinase activity represents either beta-ARK or a closely related member of the receptor specific kinase enzyme family. PMID- 8498512 TI - Secretin receptors mediating rat forestomach relaxation. AB - Frozen sections of the rat stomach were incubated with 125I-labeled porcine secretin, and then secretin binding sites were localized by autoradiography. Saturable binding was observed only in the muscularis externa (circular and longitudinal smooth muscle layers) of the proximal nonglandular forestomach. Saturable binding was quantitated by densitometry. 125I-porcine secretin bound to a single class of high-affinity binding sites with a dissociation constant of 0.6 nM. Porcine and rat secretins were nearly equipotent in inhibiting saturable 125I porcine secretin binding, and vasoactive intestinal polypeptide, peptide histidine-isoleucine, and glucagon were much weaker. Carbachol (100 microM) stimulated a sustained increase in tension in forestomach muscle in vitro, and porcine secretin caused relaxation of this stimulated contraction. We conclude that rat forestomach smooth muscle expresses a high-affinity specific secretin binding site that mediates relaxation. This putative secretin receptor may mediate some of the actions of secretin on gastric motility. PMID- 8498513 TI - Capsaicin treatment blocks development of hyperkinetic circulation in portal hypertensive and cirrhotic rats. AB - To investigate a possible role of primary afferent innervation in the pathogenesis of hyperkinetic circulation in cirrhosis or portal hypertension, we used capsaicin to denervate the primary afferent nerves. Rat pups were injected with capsaicin (50 mg/kg) or a vehicle and were allowed to grow. When they reached young adulthood, operations to induce portal hypertension by portal vein stenosis or cirrhosis by bile duct ligation were performed. A control group had sham operation. Cardiac output and regional blood flows were measured in unrestrained conscious rats by radioactive microspheres. Capsaicin-treated portal hypertensive and cirrhotic rats had cardiac output and systemic vascular resistance similar to sham-operated rats, whereas the vehicle-treated portal hypertensive and cirrhotic rats showed the hyperkinetic circulation. No hemodynamic effect of capsaicin on sham-operated rats was detected. Capsaicin treated rats did not demonstrate a splanchnic or renal hyperemia, but the percentage of cardiac output in these vascular beds was similar to controls. These results suggest that capsaicin treatment blocked the generalized vasodilatation in cirrhotic and portal hypertensive rats. Arterial pressure and heart rate were not modified in any group. These results show that denervation of capsaicin-sensitive primary afferent nerves in cirrhotic and portal hypertensive rats blocked the expected development of hyperkinetic circulation. We conclude that primary afferent innervation may be important in the genesis of hyperdynamic circulation in portal hypertension and cirrhosis. PMID- 8498514 TI - Cl-HCO3 and Cl-OH exchanges mediate Cl uptake in apical membrane vesicles of rat distal colon. AB - This study describes Cl-HCO3 and Cl-OH exchanges as the mechanism for Cl uptake by apical membrane vesicles (AMV) of rat distal colon. Although HCO3 gradient stimulated 36Cl uptake was additionally stimulated by the additional presence of a pH gradient, pH gradient-stimulated 36Cl uptake was not further enhanced by a HCO3 gradient. HCO3 gradient-stimulated and OH gradient-stimulated 36Cl uptake was not inhibited by voltage clamping, with K and its ionophore valinomycin, but was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, an anion exchange inhibitor, with an apparent inhibitory constant of 7.8 and 106.0 microM, respectively. Increasing intravesicular OH concentration in the absence of HCO3 (with fixed extravesicular Cl concentration) yielded a sigmoidal curve for 36Cl uptake. In contrast, increasing intravesicular OH concentration in the presence of equimolar intra- and extravesicular HCO3 (25 mM) yielded a saturable hyperbolic curve. Increasing extravesicular Cl concentration saturated both HCO3 gradient-stimulated and OH gradient-stimulated 36Cl uptake, with a kinetic constant for Cl of approximately 11.9 and 22.6 mM, respectively. We conclude that Cl uptake in AMV of rat distal colon occurs via two separate anion (Cl-HCO3 and Cl-OH) exchange processes. We speculate that one of these two anion exchanges may be responsible for transcellular Cl movement, while the other may be important in the regulation of intracellular pH homeostasis. PMID- 8498515 TI - Hepatocyte horseradish peroxidase uptake is saturable and inhibited by mannose terminal glycoproteins. AB - In the liver, horseradish peroxidase (HRP) is thought to be taken up via mannose receptor-mediated endocytosis by non-parenchymal cells (NPC) and via fluid-phase endocytosis by hepatocytes. When we attempted to inhibit NPC uptake of HRP with mannan in the whole perfused rat liver, > 80% of HRP uptake was eliminated. Liver cell fractionation revealed that mannan not only inhibited HRP uptake by NPC (91%) but also by hepatocytes (81%). In isolated hepatocytes, HRP uptake was linear over 60 min and saturable in the range of 0 to 200 mg/l (Vmax = 4.3 ng.mg protein-1.min-1; Km = 8.3 mg/l). Mannan inhibited uptake competitively (Ki = 2.0 2.5 mg/l). At high concentrations of HRP, a nonsaturable component of HRP uptake became evident (k = 2.8 pg.mg protein-1.min-1.mg HRP-1.l-1). Hepatocyte uptake of HRP was inhibited by other glycoproteins and glycopeptides with mannose-terminal groups, as well as by mannan, but not by asialofetuin (ASF) or bovine serum albumin. Hepatocyte uptake of 125I-labeled ASF, which is taken up via the asialoglycoprotein receptor, was saturable and not inhibited by mannan. HRP binding to hepatocytes, determined at 4 degrees C, was also inhibited by mannan. Quantification of contamination of the parenchymal cell fraction by NPC by cell counting and by pronase digestibility suggested our results could not be explained by contamination of hepatocytes by NPC. At concentrations used for most morphological studies (1,000-10,000 mg/l), fluid-phase endocytosis accounts for much of HRP uptake. However, at low concentrations, a saturable low-capacity mechanism is responsible for most HRP uptake by the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498516 TI - Biological activity of metabolites of PGD2 on canine proximal colon. AB - The responses of the canine colonic epithelium to the metabolites of prostaglandin D2 (PGD2) were compared with those elicited by the parent prostanoid. Dose-response relations to PGD2 showed three distinct patterns: 1) a dose-dependent decrease in short-circuit current (Isc) at lower concentrations followed by a dose-dependent increase at higher concentrations; 2) dose-dependent decreases, with no increase even at the highest concentrations tested; and 3) dose-dependent increases in Isc, with no decreases at any concentration. The colon responded differently to the two enzymatically derived metabolites 13,14 dihydro-15-keto-PGD2 (DK) and 11 beta-PGF2 alpha. The former consistently produced only dose-dependent decreases in Isc, while the latter elicited only dose-dependent increases. Pretreatment of tissues with 11 beta-PGF2 alpha altered the responses to PGD2 such that only decreases were noted. Conversely, pretreatment with DK caused PGD2 to elicit only increases in Isc. The nonenzymatically derived PGJ2 elicited responses comparable to those seen with PGD2. Pretreatment of tissues with indomethacin abolished responses to 11 beta PGF2 alpha as well as its isomer, PGF2 alpha, suggesting the involvement of a cyclooxygenase product. Responses to PGE2 were, however, amplified. Cross desensitization was noted between the two isomers. Tissues desensitized to either 11 beta-PGF2 alpha or PGF2 alpha were responsive to DK as well as PGE2; however, tissues desensitized to PGE2 were unresponsive to 11 beta-PGF2 alpha. Thus the canine colonic epithelium responds not only to PGD2 but also to its derived metabolites. Variability in the response to PGD2 between animals could stem from differences at the receptor level and/or differential production of these metabolites. PMID- 8498517 TI - Characteristics of basolateral Cl- transport by gastric surface epithelium in Necturus antral mucosa. AB - Conventional and ion-selective microelectrodes were used to characterize transport of Cl- across the basolateral cell membranes of gastric surface epithelium in isolated preparations of gastric antrum of Necturus. Conventional, voltage-sensing electrodes were used to evaluate changes in membrane potentials and resistances during removal of Cl- from the nutrient perfusate. Liquid ion exchanger Cl(-)-selective microelectrodes were constructed and validated to measure intracellular Cl- activity (aiCl). Our data indicate that 1) aiCl (range 12-25 mM) is close to that predicted if Cl- is distributed across the cell membranes by electrochemical equilibrium, 2) aiCl is not influenced by changes in luminal Cl- content but is susceptible to changes in nutrient Cl- content, 3) Cl- conductances cannot be detected in the basolateral membrane and changes in membrane potentials do not influence aiCl, and 4) Cl- accumulation across the basolateral membrane depends on Na+ and the level of [K+] in the nutrient solution. Inhibition of K(+)-dependent Cl- accumulation, in the absence of nutrient Na+ or in the presence of the inhibitor bumetanide, was demonstrated. These findings suggest that basolateral Na(+)-K(+)-Cl- cotransport is important in regulating cell Cl- levels in surface cells of the gastric antrum in Necturus. PMID- 8498518 TI - Adaptive cytoprotection in the small intestine: role of mucus. AB - Gastric mucosal injury induced by strong irritants can be dramatically reduced by pretreating the mucosa with mild forms of the same irritant. This phenomenon has been termed "adaptive cytoprotection." The aim of the present study was to use in vivo and in vitro approaches to study adaptive cytoprotection in the small intestine using physiologically relevant concentrations of oleic acid. Anesthetized rats were instrumented for perfusion of the proximal jejunum with 10 or 40 mM oleic acid (in 20 mM sodium taurocholate). Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr labeled EDTA. Perfusion of the lumen with 40 mM oleic acid produced a 10-fold increase in 51Cr-EDTA clearance, which was not affected by a previous perfusion with 10 mM oleic acid, i.e., no adaptive cytoprotection. In another series of experiments, oleic acid was placed in the lumen rather than perfused, and mucosal epithelial integrity was assessed histologically. Intraluminal placement of 10 mM oleic acid resulted in the generation of a mucus layer over the epithelium. Subsequent placement of 40 mM oleic acid did not produce significant epithelial cell injury, i.e., adaptive cytoprotection. In in vitro studies, mucin (1, 5, and 10 mg/ml) was layered over confluent monolayers of Caco-2 cells prior to addition of 2 mM oleic acid in 4 mM sodium taurocholate. The epithelial cell injury induced by oleic acid was inhibited by mucin in a dose-dependent manner. Further studies indicate that mucin does not prevent, but simply delays, the onset of cell injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498519 TI - Gastric axial forces in experimentally delayed and accelerated gastric emptying. AB - The aim of this study was to assess the relationship between altered axial forces and gastric emptying of solids by experimentally inhibiting or stimulating gastric axial forces by intraduodenal lipid or intravenous erythromycin, respectively. In 15 healthy volunteers, we simultaneously measured gastric emptying of solids by scintigraphy, gastroduodenal motility by manometry, and forces along the longitudinal axis of the distal stomach by an axial force transducer. When 25% of the radiolabel had emptied from the stomach, subjects (n = 5 in each group) received normal saline (controls), intraduodenal lipid, or intravenous erythromycin. The test period consisted of the infusion period (10 min) and the subsequent 30 min. Lipid significantly reduced and erythromycin increased axial forces compared with control (lipid: median 0.6 N [0-1.4 interquartile range (IQR)]; erythromycin: median 18.2 N (16.5-20.5 IQR); control: median 4.7 N (3.9-5.2 IQR); P < 0.01). Similarly, antral phasic pressure activities were different relative to control. Gastric axial forces correlated significantly with gastric emptying (Spearman rank correlation = 0.86; P < 0.01). These data are consistent with the hypothesis that axial forces affect gastric emptying of solids and suggest that measurement of axial forces provides an assessment of overall gastric propulsion during the emptying of solids. PMID- 8498520 TI - Regulation of taurine transport in human colon carcinoma cell lines (HT-29 and Caco-2) by protein kinase C. AB - The effect of phorbol 12-myristate 13-acetate (PMA), a phorbol ester known to stimulate protein kinase C, on taurine transport was studied in the human colon carcinoma cell line HT-29. PMA (1 microM) was found to inhibit taurine uptake in confluent monolayers of this cell line by approximately 70% after pretreatment of the cells with the compound for 1 h (IC50 = 42.7 +/- 2.6 nM). The inhibitory effect of PMA on the taurine transporter could be confirmed by using beta alanine, another substrate for the transporter. Kinetic analysis of taurine uptake indicated that the PMA effect was associated with a decrease in the maximal velocity (954 +/- 26 vs. 676 +/- 28 pmol.10 min-1.mg of protein-1) and an increase in the Michaelis-Menten constant (9.8 +/- 0.5 vs. 13.3 +/- 1.0 microM). The inhibition of taurine uptake could be blocked by cotreatment of the cultures with staurosporine, an inhibitor of protein kinase C. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate had no effect. Treatment of the cells with PMA did not alter the uptake of leucine and lysine, stimulated the uptake of aspartic acid, and inhibited the uptake of proline. The PMA effect on taurine uptake was not prevented by cycloheximide, actinomycin D, colchicine, or cytochalasin D. Comparison of the taurine transport activity in HT-29 cells with that in Caco-2, another human colon carcinoma cell line, revealed that the latter cell line also expressed the taurine transporter but at a much reduced level (about one-fifth compared with HT-29).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498521 TI - Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell conditioned medium and PDGF. AB - In normal liver, lipocytes are the principal reservoir for retinoids, which are stored as retinyl esters. In liver injury, lipocytes activate into myofibroblast like cells, which lack retinoid. We examined mechanisms of retinoid loss using a culture model in which lipocyte activation is provoked by exposure to Kupffer cell-conditioned medium (KCM) (S.L. Friedman and M. J. P. Arthur, J. Clin. Invest. 84: 1780-1785, 1989). In lipocytes exposed to KCM, there was approximately 11-fold more retinol in medium than in untreated cells, without release of retinyl esters. Both bile salt-dependent and -independent retinyl ester hydrolase was entirely intracellular, suggesting that the increase in retinol was due to intracellular hydrolysis; activity of bile salt-independent hydrolase was increased in KCM-treated lipocytes. Release of retinol was serum dependent and inhibited 40% by antibodies to platelet-derived growth factor (PDGF). The addition of 10 nM PDGF to serum-free KCM also induced retinol release. Lipocyte expression of mRNAs for cellular retinol-binding protein, retinoic acid receptor (RAR)-alpha, and RAR-beta was unchanged after exposure to KCM. In summary, activation of cultured lipocytes by KCM is accompanied by serum- and PDGF-dependent release of retinol; a similar mechanism may underlie retinoid loss by activated lipocytes in vivo. PMID- 8498522 TI - Transcellular eicosanoid synthesis in cocultures of alveolar epithelial cells and macrophages. AB - We have examined the importance of the relative capacities for arachidonic acid (AA) liberation and oxygenation as determinants of the magnitude of transcellular eicosanoid synthesis in cocultures of [3H]AA-prelabeled alveolar macrophages (AM) and [14C]AA-prelabeled alveolar epithelial cells (AEC). Taking advantage of our previous observation that over time in culture, AEC exhibit increases in AA release (plateau at day 4) that precede increases in cyclooxygenase capacity (maximal at day 7), we studied cocultures of freshly harvested AM together with AEC at culture days 2, 4, and 7. In this model, ionophore stimulation resulted in transcellular eicosanoid synthesis via the bidirectional transfer of free AA, with AM synthesizing their exclusive 5-lipoxygenase products leukotriene B4 and 5 hydroxyeicosatetraenoic from AEC-derived AA, and AEC synthesizing their exclusive cyclooxygenase metabolites prostaglandin E2 and prostacyclin from AM-derived AA. 14C-labeled 5-lipoxygenase products were synthesized by cocultures in the rank order: day 4 > day 2 > day 7, paralleling the relative amounts of unmetabolized AEC-derived [14C]AA. Transcellular flow of [14C]AA to the AM 5-lipoxygenase pathway was also favored when the AEC cyclooxygenase pathway was inhibited with indomethacin. Inhibition of the AM 5-lipoxygenase pathway with the compound MK 886 similarly resulted in the accumulation of unmetabolized AM-derived [3H]AA and greater synthesis of 3H-labeled prostanoids. We conclude that 1) the quantity of unmetabolized AA made available by one cell is an important determinant of the extent to which the fatty acid is utilized for transcellular eicosanoid synthesis by the second cell; 2) the fate of AA derived from a donor cell is influenced by the expression of AA oxygenation pathways in both the donor cell and the recipient cell; and 3) intercellular exchange of AA favors its shunting from an inhibited oxygenation pathway to an uninhibited one. PMID- 8498523 TI - pH-induced calcium transients in type II alveolar epithelial cells. AB - Although both intracellular pH (pHi) and intracellular Ca2+ concentration ([Ca2+]i) are highly regulated and have important metabolic effects in alveolar epithelial cells, little is known about the interrelationship between these two ions in alveolar epithelial cells. The present study examined changes in [pH]i and [Ca2+]i in isolated alveolar epithelial cells using the fluorescent dyes SNARF-1 and fura-2. Basal pHi values in freshly isolated and cultured alveolar epithelial cells were 7.27 and 7.24, respectively. Resting [Ca2+]i values in freshly isolated cells (53 +/- 5 nM) were lower than those in cultured type II cells (107 +/- 21 nM). pHi increased rapidly after addition of 25 mM NH4Cl in both cultured and freshly isolated cells and then decreased back toward baseline over the following 10 min. The rise in pHi was associated with a transient increase in [Ca2+]i. Resuspension of cells in an NH4Cl-free solution resulted in rapid intracellular acidification, which recovered over the subsequent 10 min. Removal of sodium or addition of 1 mM amiloride to the external solution slowed the rate of recovery from intracellular acidification, consistent with the participation of Na(+)-H+ exchanger in this process. In freshly isolated cells, [Ca2+]i increased following acidification and then decreased as the cells recovered from an acid load. In cultured cells, [Ca2+]i also increased following acidification but then remained elevated over the subsequent 10 min. The recovery of [Ca2+]i toward baseline values in fresh cells following acidification was dependent on the presence of external sodium. These data demonstrate that both increases and decreases in pHi of alveolar epithelial cells are associated with increases in [Ca2+]i and suggest that some of the metabolic effects of altering pHi may be secondary to increases in [Ca2+]i. The dependency of [Ca2+]i recovery following acidification on external sodium raises the possibility that freshly isolated type II cells have Na(+)-Ca2+ exchangers that contribute to the regulation of [Ca2+]i. PMID- 8498524 TI - Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs. AB - We studied the relationship between mode of activation of isolated human eosinophils and in situ responsiveness in isolated tracheal smooth muscle (TSM) of guinea pigs. Human peripheral blood eosinophils were activated with either 10( 7) M phorbol myristate acetate (PMA) or 10(-6) M formyl-methionyl-leucyl phenylalanine (fMLP) + 5 micrograms/ml cytochalasin B (CYB), and activation was confirmed by measurement of eosinophil peroxidase (EPO) secretion by kinetic assay. EPO secretion was similar after activation with fMLP+CYB (10.2 +/- 3.2% of total eosinophil content) and PMA (10.0 +/- 2.8% of total content; P = NS). Topical application of 6 x 10(6) eosinophils/cm2 activated with fMLP+CYB to the TSM segment caused 0.51 +/- 0.14 g/cm active tension (AT) in five preparations (P < 0.03 vs. baseline); cells activated with PMA caused no contractile response (0.04 +/- 0.03 g/cm AT, P = NS vs. baseline). Both PMA- and fMLP+CYB-activated cells caused augmentation of muscarinic responsiveness of guinea pig trachealis. The dose of intravenous acetylcholine required to cause a threshold response (ED0.3) was -7.3 +/- 0.1 log mol/kg at baseline vs. -8.7 +/- 0.5 log mol/kg after treatment with fMLP+CYB-activated eosinophils (P = 0.05) and -6.9 +/- 0.1 log mol/kg at baseline vs. -7.5 +/- 0.1 log mol/kg after PMA-activated cells (P < 0.01). Both AT and augmented muscarinic responsiveness were blocked by pretreating the eosinophils with 200 microM A-63162, an inhibitor of 5 lipoxygenase, before activation with fMLP+CYB. We demonstrate that eosinophils activated comparably (as assessed by EPO secretion) cause augmented muscarinic responsiveness and/or direct contraction of guinea pig TSM through secretion of a product of the 5-lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498525 TI - Variable glutathione levels and expression of antioxidant enzymes in human endothelial cells. AB - We have investigated the relationship between intracellular glutathione levels and the inducibility of the mRNAs encoding the major antioxidant enzymes Cu,Zn superoxide dismutase (Cu,Zn SOD), catalase (CAT), glutathione peroxidase (GP), and the stress protein heme oxygenase (HO) following exposure of human umbilical vein endothelial cells (HUVEC) to either hypoxanthine-xanthine oxidase or 95% O2. Treatment of HUVEC with 2 and 200 microM buthionine sulfoximine (BSO) for 16 h reduced total glutathione (GSH) levels by 51 and 95%, respectively, whereas treatment with 100 microM diethylmaleate (DEM) for 24 h increased the cellular GSH content by 58%. None of these treatments affected the responsiveness of HUVEC to a subsequent oxidant challenge, in terms of antioxidant enzymes activities and mRNA levels. On the contrary, HO mRNA was significantly induced by both BSO and DEM, as well as by hyperoxia, albeit to a different extent. We conclude that intracellular redox changes do not appear to regulate the expression of the mRNAs encoding Cu,Zn SOD, CAT, and GP. Furthermore, factors other than endogenous thiols may play a role in the control of HO mRNA expression. PMID- 8498526 TI - Neutrophil-activating peptide-2 in patients with pulmonary edema from congestive heart failure or ARDS. AB - We carried out studies to determine whether the neutrophil-activation peptide-2 (NAP-2) plays a role in the recruitment and/or degranulation of neutrophils into the lungs of patients with the adult respiratory distress syndrome (ARDS) or congestive heart failure (CHF). NAP-2 precursors plus NAP-2 (beta-thromboglobulin like antigen) were measured in lung fluids and plasmas with a radioimmunoassay, and NAP-2 was separated from its precursors by high-performance liquid chromatography. Pulmonary edema fluids (PEFs) from patients with CHF contained higher concentrations of the beta-thromboglobulin-like antigen than PEFs from patients with ARDS, and bronchoalveolar lavage fluids (BALs) from patients with ARDS contained higher concentrations of beta-thromboglobulin-like antigen than BALs from normal subjects. beta-Thromboglobulin-like antigen concentration was 4.1-fold greater in PEFs from patients with CHF than in their plasmas. Chemotactically active NAP-2 was also demonstrated in PEFs but not in plasmas from patients with CHF and ARDS. These data suggest that significant platelet degranulation occurred into the lungs of the patients with CHF and that NAP-2 and other platelet constituents may contribute to fluid formation in patients with CHF. PMID- 8498527 TI - Fetal rat lung type II cell differentiation in serum-free isolated cell culture: modulation and inhibition. AB - Undifferentiated fetal rat lung epithelial cells were isolated on gestational days 15 or 17 (term 22 days) and cultured in a defined medium. On plastic, most of the cells developed structurally abnormal lamellar bodies. On a basement membrane matrix (BMM), they sequentially accumulated glycogen and formed typical lamellar bodies. Biochemical analysis of the latter indicated that they had a phospholipid composition typical of surfactant for cells on BMM but not on plastic and that surfactant protein A appeared on BMM only. Progressing maturation from day 1 to day 6 in culture was demonstrated for 17-day cells on BMM by a sevenfold increase of labeled precursor incorporation into surfactant phospholipids. Exposure to medium conditioned by 21-day fetal fibroblasts enhanced incorporation already after a 1-day culture. The antisteroid RU 486 had no effect on differentiation, whereas transforming growth factor-beta, a factor produced by lung mesenchyme at early fetal stages, inhibited it markedly. Alveolar epithelial type II cells appear to be committed early, but their maturational process would be prevented until a definite gestational stage. PMID- 8498528 TI - Characterization of monocrotaline pyrrole-induced DNA cross-linking in pulmonary artery endothelium. AB - Monocrotaline pyrrole (MCTP) is a putative, toxic metabolite of the pyrrolizidine alkaloid, monocrotaline (MCT). When given intravenously to rats, it produces a delayed and progressive injury to the vasculature of the lungs that results in pulmonary hypertension and right heart hypertrophy. Dysfunctional endothelium and vascular leak are early signs of overt injury to the lung. When administered to endothelial cell cultures, MCTP causes cell enlargement, delayed and progressive cytotoxicity, and inhibition of proliferation in surviving cells. MCTP is a bifunctional alkylating agent which binds to DNA and other macromolecules. To examine DNA-MCTP interactions in endothelium, MCTP-induced DNA cross-linking was characterized in cultures of porcine endothelial cells (PECs) derived from pulmonary artery. MCTP caused DNA cross-linking in a dose-dependent manner that was consistent with its ability to inhibit cell proliferation. PECs exposed to MCTP for 48 h developed cross-linking that was maximal at 2 days and remained significant through 10 days. Increasing the duration of PEC exposure to the medium to which MCTP had been added was associated with increased DNA cross linking. These results indicate that MCTP causes DNA cross-linking, which may explain the inhibition of cell proliferation observed in pulmonary endothelial cells in vitro. The long-lasting nature of DNA cross-linking and its dose relatedness are consistent with the delayed and progressive effects of MCTP on endothelial cells in vitro and on pulmonary vasculature in vivo. PMID- 8498529 TI - Decrease in Gs protein expression may impair adenylate cyclase activation in old kidneys. AB - The possibility that alteration in stimulatory guanine nucleotide-binding protein (Gs) expression may contribute to the blunting of renal parathyroid hormone (PTH) stimulated adenylate cyclase in aged rats was examined. Using rat cDNA probe, we identified a Gs alpha-subunit (Gs alpha) of 1.9 kb. Age did not alter the size of Gs alpha mRNA. The level of Gs alpha mRNA [normalized to poly(A)+ RNA] was decreased 23%, which was consistent with our previous report that Gs alpha protein decreased in senescence. In contrast, mRNA level of Gi alpha 2 increased with age. Level of beta-actin mRNA did not change with age. Nuclear runoff assay was performed to determine the transcription rate of Gs mRNA. Synthesis of poly(A)+ RNA and total RNA was reduced 39% and 37%, respectively, in nuclei prepared from old kidney, which suggested a general decline in RNA synthesis capacity in old rats. Our results also showed the transcription rate of Gs alpha mRNA in aged rats was reduced 89%, a decrease far exceeding that observed for total RNA or poly(A)+ RNA. We concluded that the decrease in steady-state level of Gs alpha mRNA was specific and probably was due to a reduction in the transcription activity. Thus alteration in Gs transcription may contribute, at least in part, to the impaired renal adenylate cyclase activation in aged rats. PMID- 8498530 TI - LPS-induced MCP-1, IL-1 beta, and TNF-alpha mRNA expression in isolated erythrocyte-perfused rat kidney. AB - The capacity of the lipopolysaccharide (LPS)-stimulated isolated erythrocyte perfused rat kidney (IEPK) to produce monocyte chemoattractant protein-1 (MCP-1), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) mRNA was investigated. The IEPK was chosen to exclude the influence of circulating neutrophils and monocytes that can produce both these mediators when exposed to LPS. The control minimal LPS group (LPS < 10 pg/ml) showed a small increase in mRNA expression for MCP-1, IL-1 beta, and TNF-alpha in the cortex and medulla after 80 min of perfusion when compared with the unperfused left kidney in which no IL-1 beta or TNF-alpha mRNA and only minimal amounts of MCP-1 mRNA were detected. LPS stimulation (1 microgram/ml for 40 or 80 min) increased MCP-1, IL-1 beta, and TNF-alpha mRNA expression, which was found predominately in peritubular capillary endothelial cells by in situ hybridization. The changes were not due to a marked perturbation of LPS on renal hemodynamics. The renal vascular resistance (RVR) remained constant (40 min LPS exposure) or increased only slightly during the last 5-10 min (80 min LPS exposure) compared with a progressive increase in RVR of the minimal LPS group. The hemodynamic effects of LPS on the IEPK appear to counteract the gradual increase in RVR seen in the minimal LPS group. PMID- 8498531 TI - K infusion corrects thick ascending limb Cl reabsorption in K-depleted rats by an aldosterone-independent mechanism. AB - Others have provided evidence that thick ascending limb (TAL) NaCl reabsorption is aldosterone dependent in adrenalectomized animals. In rats fed a K-free diet, plasma K concentration ([K]) is reduced and plasma aldosterone concentration [Aldo] is decreased. Because aldosterone release is regulated by extracellular fluid (ECF) [K], the purpose of the present study was to determine whether aldosterone deficiency mediates inhibition of TAL NaCl transport in K-depleted rats (K-Dep). Cl reabsorption was measured in functionally isolated loop segments microperfused in vivo (22 nl/min) using a modified perfusate that minimizes proximal nephron reabsorption. The results of our studies show that the defect in TAL Cl reabsorption in K-Dep rats is quantitatively significant and can be rapidly reversed by the acute systemic infusion of K. However, acute administration of aldosterone, in the presence of sustained K-Dep, failed to reverse the impairment in TAL Cl reabsorption in K-Dep rats. Furthermore, acute infusion of K, in the presence of an aldosterone antagonist, in K-Dep rats rapidly corrected the defect in TAL Cl reabsorption. Additional studies showed that despite normalization of ECF [K] by acute K infusion in K-Dep rats, plasma [Aldo] failed to increase. In contrast, acute infusion of KCl in control rats increased plasma [Aldo] by 46%, but Cl reabsorption was unchanged. In summary, these results provide conclusive evidence that the correction of defective TAL Cl reabsorption in response to the acute administration of K in K-Dep rats occurs via an aldosterone-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498532 TI - Regulation of renal epithelial cell endocytosis of calcium oxalate monohydrate crystals. AB - The earliest events in the formation of kidney stones are unknown. The most common crystal in kidney stones, calcium oxalate monohydrate (COM), when added to cultures of monkey kidney epithelial cells (BSC-1 line), was internalized by 19% of the cells after 30 min. COM crystal endocytosis was enhanced by serum, ADP, and epidermal growth factor, which are potent mitogens for these cells. Endocytosis of COM crystals was inhibited by diverse molecules including Tamm Horsfall glycoprotein (THP), the tetrapeptide arginine-glycine-aspartic acid serine, fibronectin, transforming growth factor-beta 2, and heparin. The capacity of THP, fibronectin, or heparin to inhibit endocytosis was mediated by an interaction of these molecules with cells, not by coating the crystals. Thus renal epithelial cell endocytosis of COM crystals can be regulated by diverse molecules including THP, the most common protein found in human urine. Crystal endocytosis and subsequent cellular responses could be important pathogenic steps in nephrolithiasis. PMID- 8498533 TI - Effect of plasma prolactin on sweat rate and sweat composition during exercise in men. AB - We investigated the role of the exercise-induced elevation of plasma prolactin (PRL) concentration on sweat rate and composition during prolonged exercise in men. Two groups of healthy young males (20-26 yr old) showing a high (high responders; n = 8) or a low (low responders; n = 7) response of plasma PRL concentration to exercise were studied during a 60-min period of exercise on a cycle ergometer (65% maximum O2 consumption) in warm conditions (26.2 +/- 0.1 degrees C; 57 +/- 1% relative humidity), 1 h after receiving 1.25 mg bromocriptine (BRC) per os or a placebo. In high responders, administration of BRC totally abolished the threefold increase in plasma PRL observed in response to exercise with placebo [placebo, 10 +/- 2 (rest) and 30 +/- 2 micrograms/l (exercise); BRC, 9 +/- 1 (rest) and 8 +/- 1 microgram/l (exercise)]. The latter was associated with a significant decrease in sweat rate (2.7 +/- 0.5 to 1.9 +/- 0.3 microliter.cm-2.min-1) and a significant increase in sweat Na+ concentration (57 +/- 7 to 68 +/- 5 mmol/l). BRC also reduced the small response in plasma PRL concentration observed in low responders [placebo, 10 +/- 1 (rest) and 15 +/- 1 microgram/l (exercise); BRC, 9 +/- 1 (rest) and 7 +/- 1 microgram/l (exercise)], but this was not associated with any change in sweat rate (2.2 +/- 0.2 to 1.9 +/- 0.3 microliter.cm-2.min-1) or in sweat Na+ concentration (63 +/- 10 to 64 +/- 9 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498534 TI - Short-term effect of aldosterone on vasopressin-sensitive adenylate cyclase in rat collecting tubule. AB - Because previous studies indicated that, in the rat collecting tubule, vasopressin (AVP)-sensitive adenylate cyclase (AC) is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such a control also exists in the short term. Therefore, we investigated the in vivo and in vitro effects of aldosterone on AC activity in cortical and outer medullary collecting tubules (CCD and OMCD, respectively) from adrenalectomized rats. Injection of aldosterone (10 micrograms/kg body wt) to adrenalectomized rats restored within 3 h AVP-sensitive AC activity in the CCD and OMCD up to the levels observed in the corresponding segments of adrenal intact rats. Similarly, incubating CCD or OMCD from adrenalectomized rats for 2.5 h in the presence of 10(-8) M aldosterone enhanced AVP-sensitive AC activity up to values similar to those found in normal rats. In vitro stimulation of AVP sensitive AC activity was dose dependent with regard to aldosterone [apparent affinity constant (K0.5) approximately 10(-9) M], appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. In addition, it was totally abolished by the antimineralocorticoid spironolactone, whereas the specific glucocorticoid antagonist RU 38486 had no effect. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in that process. PMID- 8498535 TI - Endothelin-1 and endothelin-3 binding to rat nephrons. AB - The existence of endothelin (ET) receptor subtypes has recently been implicated in the different biological effects of ET in various tissues. Indeed, the cDNAs for two types of ET receptors, ETA and ETB, have been cloned. To further gain insights into ET function in the kidney we examined 125I-labeled ET-1 and ET-3 binding to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts as well as glomeruli showed moderate binding. There was low, although not significant, ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of binding of ET-1 and ET-3 using cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3; apparent dissociation constants were 2.05 +/- 0.72 and 2.58 +/- 0.32 nM, and maximal binding capacity values were 0.408 +/- 0.058 and 0.511 +/- 0.047 fmol/mm, respectively. Displacement of 125I-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Furthermore, a specific ETB agonist, BQ 3020, almost completely inhibited 125I-ET 1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ 123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally. PMID- 8498536 TI - Organic osmolytes in acute hyponatremia. AB - The defense of brain volume during hyponatremia cannot be explained by the losses of brain sodium and potassium. We have examined the brain losses of organic osmolytes in rats after 24 h of severe hyponatremia induced by the administration of vasopressin and 5% dextrose in water. Normonatremic controls and animals with intermediate plasma sodium concentration ([Na]) were produced in vasopressin treated animals by the administration of isocaloric gavages containing varying amounts of NaCl and free water. The animals were killed at 24 h by decapitation, and one brain hemisphere was quickly frozen in liquid nitrogen for organic osmolyte determinations. When compared with controls (plasma [Na] = 139 +/- 1.5 mM), hyponatremic animals (plasma [Na] = 96 +/- 1 mM) had significantly reduced brain contents for sodium, potassium, chloride, glutamate, myo-inositol, N acetylaspartate, aspartate, creatine, taurine, gamma-aminobutyric acid, and phosphoethanolamine. Plasma [Na] was highly correlated (P < 0.001) with the brain contents for sodium, potassium, and organic osmolytes. Whereas the observed increase in brain water during hyponatremia was only 4.8%, by calculation, brain swelling without brain organic osmolyte losses would have been 11%, an amount that jeopardizes survival. PMID- 8498537 TI - Ammonium and bicarbonate transport in isolated perfused rodent ascending limbs of the loop of Henle. AB - Ammonium accumulates in the renal medullas of antidiuretic animals, presumably due to countercurrent multiplication, driven by NH4+ absorption from ascending loops of Henle in the outer and inner medulla. Active absorption of NH4+ occurs in the thick ascending limb (TAL). But the passive transport properties of NH3 in the TAL and the transport of ammonium or HCO3- in the ascending thin limb (ATL) have not been studied in rodents. To investigate the potential role of the ascending limb segments in medullary accumulation of ammonium, we perfused isolated subsegments of the chinchilla ATL and of the rat ATL and TAL. After imposing concentration gradients of total ammonia or total CO2 across ATL subsegments, we found very high rates of transfer of both substances, implying that at physiological flow rates the tubule luminal fluid quickly equilibrates with the interstitium. In the medullary TAL, we found a passive NH4+ permeability of 17 x 10(-5) cm/s but a relatively low NH3 permeability of < 0.003 cm/s. The low NH3 permeability prevents backleak of NH3 when NH4+ is actively transported from the lumen. We conclude that the ATL acts as an equilibrating segment and the TAL has special permeability properties that enhance net ammonium absorption and therefore enhance medullary ammonium accumulation. PMID- 8498538 TI - Endothelin activation of phospholipase D: dual modulation by protein kinase C and Ca2+. AB - Previous work from this laboratory has identified an endothelin (ET) type A (ETA) receptor on cultured rat renal medullary interstitial cells (RMIC), coupled to phosphatidylinositol-specific phospholipase C (PI-PLC), dihydropyridine insensitive receptor-operated Ca2+ channels, and phospholipase A2. The current studies explored a role for ET stimulation of phosphatidylcholine-specific phospholipase D (PC-PLD) in intracellular signaling of this cell type. ET stimulated PLD activation, as measured by phosphatidic acid (PA) or phosphatidylethanol (PEt) accumulation, in a time- and concentration-dependent manner. Inhibition of diacylglycerol (DAG) kinase by ethylene glycol dioctanoate or 6-(2)4-[(4-fluorophenyl)-phenylmethylene]-1-piperadinyl]ethy l-7-methyl-5H - thiaxolo-[3,2-alpyrimidin]-5-one (R 59022) failed to blunt PA accumulation, indicating that PLD, and not DAG, was the source of PA. Inhibition of PA phosphohydrolase (PAP) by propranolol increased late accumulation of PA, suggesting that the prevailing metabolic flow was in the direction of PA to DAG. Phorbol 12-myristate 13-acetate (PMA) augmented ET-evoked PEt accumulation, whereas downregulation of protein kinase C (PKC) obviated agonist-induced PEt production. PMA augmentation of PLD activity proceeded independent of cytosolic free Ca2+ concentration. Ca2+ derived from either intracellular or extracellular sources enhanced ET-related PEt accumulation but was without effect in PKC downregulated cells. Collectively, these observations indicate that ET stimulates PLD production in RMIC. PKC is the major regulator of this process, with Ca2+ playing a secondary, modulatory role. In addition, these data suggest that PC-PLD is coupled to the ETA receptor. PMID- 8498539 TI - Activity of 11 beta-hydroxysteroid dehydrogenase in toad bladder: effects of 11 dehydrocorticosterone. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) transforms circulating glucocorticoids to their "biologically inert" 11-dehydro derivatives. Isoforms of 11 beta-OHSD with different cofactor requirements and biochemical properties [Michaelis constant (Km) and maximal velocity (Vmax)] exist in the kidney. Since epithelial cells derived from the toad bladder also contain this enzyme, we wished to further characterize its properties in prepared cell homogenates. 11 beta-OHSD from toad bladder demonstrated a clear preference for NAD+ over NADP+ as a cofactor similar to that observed in renal cortical collecting duct (CCD) cells. Furthermore, 11 beta-OHSD had a rapid onset of action. The apparent Km for corticosterone was 16.3 x 10(-8) M, a value comparable to that observed for enzyme from CCD, and a Vmax of 4.8 x 10(-12) mol.mg protein-1.min-1. The end product, 11-dehydrocorticosterone (compound A), influenced enzyme activity; it increased 11 beta-OHSD activity at corticosterone concentrations below the apparent Km for the enzyme and inhibited 11 beta-OHSD activity at corticosterone concentrations above the Km for the enzyme. The inhibitory effects of compound A appeared noncompetitive with an apparent equilibrium constant (Ki) of 2.8 x 10( 7) M. Consistent with its inhibitory action on 11 beta-OHSD, compound A (10(-6) M) enhanced the short-circuit current response to corticosterone (10(-7) M) in the intact toad bladder (experimental 2.03 +/- 0.33 vs. control 1.40 +/- 0.17 times above baseline; n = 7, P < 0.01). Thus 11 beta-OHSD in toad bladder resembles the isoform found in CCD, and compound A may be biologically important as a regulator of 11 beta-OHSD. PMID- 8498540 TI - Effect of morphine on uptake of immunoglobulin G complexes by mesangial cells and macrophages. AB - Focal glomerular sclerosis is the predominant renal lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the uptake of immunoglobulin G (IgG) complexes by cultured mesangial cells (MC) and macrophages (MP). Pre-incubation of morphine (10(-6) M) decreased uptake of IgG complexes [morphine, 66,577 +/- 6,248 vs. control, 95,735 +/- 5,227 counts.min-1 (cpm).mg protein-1; P < 0.02] by MC. Morphine (10(-4)-10(-6) M) also inhibited (P < 0.01) uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-labeled low-density lipoprotein by MC. MP pretreated with morphine (10(-6) M) also showed significantly (P < 0.02) lower uptake of IgG complexes (control 94,959 +/- 4,980 vs. morphine, 58,360 +/- 11,608 cpm/mg protein). Binding studies carried out at 4 degrees C on MC and MP indicated that morphine did not modulate surface binding of IgG complexes. Naloxone, a morphine antagonist, also produced a rather decreased (P < 0.05) uptake of IgG complexes by both MP and MC and did not inhibit the effect of morphine on the uptake of IgG complexes. In vivo studies indicated that morphine-treated rats had a higher (P < 0.05) accumulation of aggregated human IgG complexes (125I-labeled ahIgG) in their glomeruli when compared with untreated rats (control rats, 256,929 +/- 40,008 cpm/g protein vs. experimental rats, 398,317 + 51,512 cpm/g). Increased accumulation of 125I-ahIgG in the glomeruli from morphine-treated rats may either be related to increased delivery of 125I-ahIgG into the mesangium or be a result of decreased drainage of 125I-ahIgG from the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498541 TI - Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy. AB - The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction. PMID- 8498542 TI - Aluminum inhibits bone nodule formation and calcification in vitro. AB - Cells isolated from neonatal mouse calvariae can be induced to form mineralized nodules after exposure to ascorbic acid and beta-glycerophosphate. To determine whether aluminum inhibits nodule formation and subsequent mineralization, cells isolated from neonatal mouse calvariae were induced to form nodules and incubated with increasing concentrations of aluminum (10(-7) to 10(-5) M). Compared with control and 10(-7) M aluminum-supplemented cultures, the number of nodules formed and the number of nodules calcified were reduced in cells incubated with 10(-6) and 10(-5) M aluminum. The cumulative net calcium uptake into the nodules and their final calcium content were also decreased with 10(-6) and 10(-5) M aluminum. After 10 and 18 days of incubation, aluminum did not affect DNA synthesis or release of alkaline phosphatase but significantly inhibited collagen production. Thus aluminum induced a dose-dependent inhibition of nodule formation and calcification that may be related to its inhibition of collagen production. PMID- 8498543 TI - Enhanced HCO3 secretion by distal tubule contributes to NaCl-induced correction of chronic alkalosis. AB - Free-flow micropuncture studies show depressed net HCO3 reabsorption in the surface distal tubule of rats undergoing correction of chronic metabolic alkalosis induced by NaCl infusion. The present studies used in vivo microperfusion of the rat distal tubule to investigate whether the described reduction in net HCO3 reabsorption was due to decreased luminal H+ secretion or to increased HCO3 secretion. Animals with correcting alkalosis had higher HCO3 secretion in this nephron segment than did animals with maintained alkalosis regardless of whether the perfusing solution was initially Cl free (-27.6 vs. 16.6 pmol.mm-1.min-1, P < 0.01) or contained 40 mM Cl (-31.5 vs. -23.0 pmol.mm 1.min-1, P < 0.01); H+ secretion was not different between animals with correcting and maintained alkalosis. Animals without alkalosis (control) demonstrated no differences in H+ or HCO3 secretion in response to NaCl infusion. These studies demonstrate that enhanced HCO3 secretion mediates the depressed net HCO3 reabsorption observed in the distal tubule of rats undergoing NaCl-induced correction of chronic metabolic alkalosis. PMID- 8498544 TI - Mechanism of ischemia-enhanced aminoglycoside binding and uptake by proximal tubule cells. AB - Preceding ischemia or concurrent hypotension is known to enhance aminoglycoside nephrotoxicity; however, the underlying mechanisms responsible have not been determined. To investigate the effect of preceding mild ischemia on cellular gentamicin handling, brush-border membrane vesicle binding and in vivo cellular gentamicin uptake were quantified using [3H]gentamicin as a tracer. Fifteen minutes of ischemia resulted in a marked increase in apical membrane gentamicin binding (2.8 +/- 0.4 vs. 4.9 +/- 0.8 nmol/mg protein, P < 0.01). This increase was associated with an increased number of binding sites (3.7 +/- 0.3 vs. 9.1 +/- 2.3 nmol/mg protein, P < 0.01) and a reduced binding affinity (11.8 +/- 2.2 vs. 27.7 +/- 10.4 microM, P < 0.01). This increase in gentamicin binding was accompanied by alterations in apical membrane phospholipids including a doubling of phosphatidylinositol (PI) levels (13.8 +/- 0.4 vs. 27.5 +/- 3.1 nmol/mg protein, P < 0.01). Furthermore, treatment of apical membrane vesicles with PI specific phospholipase C markedly reduced the difference in gentamicin binding between paired control and ischemic membrane fractions. Increased gentamicin binding was associated with increased in vivo uptake of gentamicin by S1/S2 and S3 cells. Outer cortical uptake of gentamicin increased from 2.18 +/- 0.39 to 2.68 +/- 0.27 nmol/mg protein (P < 0.01) after 15 min of ischemia and 4 h of reperfusion. Juxtamedullary uptake also increased from 1.39 +/- 0.31 to 1.75 +/- 0.12 nmol/mg protein (P < 0.01). Immunocytochemical techniques, utilizing immunogold labeling, showed gentamicin was taken up via the receptor-mediated endocytic pathway by S1/S2 and S3 cells. After ischemic injury gentamicin was localized in abnormal intracellular accumulations in S3 but not S1 or S2 cells. Taken together, these data indicate ischemia results in a marked increase in apical gentamicin binding due to increases in apical PI content. This is associated with increased internalization by S1/S2 and S3 cells and abnormal intracellular compartmentalization of gentamicin within S3 cells. PMID- 8498545 TI - Effects of IGF-I on renal function in patients with chronic renal failure. AB - Insulin-like growth factor I (IGF-I) has been shown to increase glomerular filtration rate and renal plasma flow in rats and humans with normal renal function. However, rats with reduced renal function are resistant to these effects. To determine whether IGF-I affects glomerular filtration rate and renal plasma flow in humans with reduced renal function, we administered recombinant human IGF-I (rhIGF-I) to patients with moderate chronic renal failure. Four patients whose baseline inulin clearances were 21.9, 23.2, 34.9, and 55.1 ml.min 1.1.73 m-2 were placed on a 1 g.kg-1.day-1 protein diet and studied over a 10-day period (0-10). On days 4-7, 100 micrograms/kg of rhIGF-I was subcutaneously administered twice daily to the patients. The effects of rhIGF-I on levels of circulating IGF-I, inulin clearance, p-aminohippurate (PAH) clearance, kidney volume, plasma glucose, plasma and urine calcium and phosphate, and urine sodium and protein were determined. Administration of rhIGF-I increased levels of circulating IGF-I, inulin clearances, PAH clearances, and kidney size in each of the four patients receiving the growth factor. IGF-I did not cause weight gain, natriuresis, proteinuria, or hypoglycemia. Plasma calcium and phosphate were not affected by rhIGF-I. However, the percent tubular reabsorption of filtered phosphate was increased. We conclude that administration of rhIGF-I can enhance glomerular filtration rate and renal plasma flow at least in some humans with moderately reduced renal function. The enhancement is associated with an increase in kidney volume. PMID- 8498546 TI - Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs. AB - The objective of the present study was to characterize the role of adenosine in myocardial ischemic preconditioning in the canine heart. Preconditioning with 5 min of ischemia resulted in a marked reduction in infarct size after 60 min of left circumflex coronary artery occlusion and 5 h of reperfusion in barbital anesthetized dogs compared with dogs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.05). Pretreatment with either the nonselective adenosine receptor antagonist PD 115199 or the selective adenosine A1 receptor antagonist 8 cyclopentyl-1,3-dipropylxanthine blocked this protective effect, although in the absence of preconditioning neither of the antagonists affected infarct size. Intracoronary infusion of two different doses of adenosine or dipyridamole over a 5-min period before a prolonged 60-min occlusion period did not mimic preconditioning; however, intracoronary infusion of a combination of adenosine and dipyridamole produced a significant reduction in infarct size (13.6 +/- 4.1%), which was abolished by pretreatment with the ATP-dependent potassium (KATP) channel antagonist glibenclamide. These results suggest that activation of adenosine A1 receptors produces myocardial preconditioning in the canine heart by opening KATP channels. PMID- 8498547 TI - Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats. AB - Arterial smooth muscle from hypertensive rats shows an increased membrane permeability to K+ that depends on Ca2+ influx. To define the mechanism of this membrane alteration, we tested the hypothesis that Ca(2+)-dependent K+ current (IK(Ca)) is increased in arterial muscle membranes from genetically hypertensive rats. Single-channel K+ currents measured in cell-attached and inside-out aortic membrane patches from spontaneously hypertensive rats (SHR) were compared with those from normotensive Wistar-Kyoto rats (WKY). Inside-out patches from both rat strains showed a predominant 225 pS, Ca(2+)- and voltage-dependent K+ channel in symmetrical 145 mM KCl solutions, which was blocked by tetraethylammonium [concentration for half-maximal block (IC50) < or = 0.3 mM]. In cell-attached patches of aortic muscle cells bathed in physiological salt solution, this channel [IK(Ca) channel] showed a fivefold higher open-state probability (NPo) in SHR as compared with WKY. This increased NPo of SHR IK(Ca) channels in membranes of intact aortic muscle cells was not correlated with an altered membrane potential in current-clamped SHR myocytes or with changes in cytosolic free Ca2+ concentration in fura-2-loaded aortic muscle cells. However, inside-out aortic membrane patches from SHR showed more detected IK(Ca) channels per patch, a higher IK(Ca) channel NPo, and a greater total patch current than their WKY counterparts. Further analysis revealed a greater Ca2+ sensitivity of SHR than WKY IK(Ca) channels. These results suggest that IK(Ca) channel function is altered in isolated membrane patches of arterial muscle from genetically hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498548 TI - A role for nitric oxide in active thermoregulatory vasodilation. AB - We have shown previously that an increase in ear blood flow velocity (EBF) in the conscious, chronically instrumented rabbit during whole body heating (WBH) involves active neurogenic vasodilation that is abolished by local nerve block. This study was designed to test the potential role of nitric oxide (NO) in rabbit ear neurogenic vasodilation during hyperthermia. Rabbits were instrumented for the measurement of arterial pressure, heart rate, and EBF (Doppler ultrasound). A catheter was also placed in the left lingual artery for administration of drugs to the left ear. WBH was achieved by circulating warm water through a rubber pad placed around the rabbit. Internal temperature was measured with a rectal thermocouple. During WBH, bolus injections of N omega-nitro-L-arginine (L-NNA), a false substrate for the formation of NO, were given via the lingual artery (10( 5) M, 4-5 ml total) to determine whether NO was involved in the increase in EBF. During WBH, left ear vascular conductance (EVC) increased from 0.07 +/- 0.03 to 5.87 +/- 0.73 kHz/100 mmHg and right EVC from 0.20 +/- 0.13 to 4.49 +/- 1.73 kHz/100 mmHg. When EVC was maximum, L-NNA was administered into the left lingual artery. EVC began to decrease after a latency of 23 min. At 56 +/- 8 min, left and right EVC had decreased to 0.18 +/- 0.10 and 0.23 +/- 0.11 kHz/100 mmHg, respectively (P < 0.05). Subsequent infusions of L-arginine, the true substrate for NO formation, restored EVC. These results suggest that NO is involved in active vasodilation during heating in the rabbit ear. PMID- 8498549 TI - Hypercapnia slightly raises blood volume and sizably elevates flow velocity in brain microvessels. AB - The increase in local cerebral blood flow (LCBF) caused by hypercapnia may be mainly accomplished by raising the velocity of plasma and/or red blood cell (RBC) flow through the microvessels and not by perfusing more capillaries. This suggestion was tested in awake rats exposed to 8% CO2 and in control rats. LCBF was measured by the 14C-labeled iodoantipyrine method. The volume of blood in small parenchymal microvessels was estimated from the distribution spaces of 125I labeled serum albumin (RISA) and 55Fe-labeled RBCs. Hypercapnia elevated LCBF 2.0 to 3.5-fold in the 40 brain areas studied, marginally raised the RBC spaces, and significantly increased the RISA and whole blood distribution spaces (approximately 25 and 19%, respectively). These changes in microvessel distribution volumes could be the result of perfusing a slightly larger fraction of capillaries (recruitment), increasing microvessel diameter somewhat, or both. With hypercapnia, the mean transit times fell to approximately 45% of control, which indicated that LCBF was mainly increased by raising the velocity of RBC and plasma flow through already perfused microvessels. Overall, few, if any, capillaries or other microvessels were recruited by hypercapnia. PMID- 8498550 TI - Protective effects of histidine during ischemia-reperfusion in isolated perfused rat hearts. AB - We investigated the efficacy of histidine in reducing ischemia-reperfusion (I/R) induced myocardial injury in isolated perfused rat hearts. In I/R hearts, the contractile function and coronary flow were 59 +/- 10 and 78 +/- 6% of control. Perfusion with histidine resulted in significant increase in contractility (94 +/ 4%) and coronary flow (92 +/- 4%). The incidence of arrhythmias during reperfusion was 100% (10 out of 10) in the I/R hearts with an average duration of 12.22 +/- 1.55 (SE) min. The duration of arrhythmias was shortened to 8.24 +/- 1.46, 2.15 +/- 0.9, and 2.49 +/- 1.50 min with 10, 25, and 50 mM histidine, respectively. The duration of sinus rhythm increased from 6.26 +/- 1.56 min in I/R hearts to 10.66 +/- 1.55, 14.99 +/- 1.61, and 17.18 +/- 0.95, and 11.73 +/- 0.93 min after perfusion with 10, 25, and 50 mM histidine, and superoxide dismutase (SOD)-catalase-mannitol, respectively. Electron microscopy revealed significant ultrastructural damage of myocytes in I/R hearts, which included swelling of the mitochondria and disruption of both the sarcolemma and the myofibrils. Histidine reduced the ultrastructural damage in a dose-dependent fashion. In general, the protective effect of histidine was superior than SOD catalase-mannitol. We conclude that histidine protects myocardium against I/R damage most likely by a singlet oxygen scavenging mechanism. PMID- 8498551 TI - Albumin modulation of paracellular permeability of pig vena caval endothelium shows specificity for pig albumin. AB - We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had Lp,e values of 1.30 +/- 0.81 x 10(-7) cm.s-1.cmH2O-1 (n = 9) and Re values of 13.8 +/- 2.6 omega.cm2 (n = 3). Vessels kept in PSA had Lp,e values of 0.257 +/- 0.125 x 10(-7) cm.s 1.cmH2O-1 (n = 5) and Re values of 21 +/- 6.3 omega.cm2 (n = 4). The differences between Lp,e and Re in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of Lp,e. Lower Lp,e and higher Re in PSA as compared with those in BSA suggest that specificity for the autologous albumin is a general phenomenon in mammalian endothelium and that albumin binding to specific sites is associated with its permeability effect. PMID- 8498552 TI - Cardiac effects of acetylcholine in rat hearts: role of endothelium-derived relaxing factor and prostaglandins. AB - We examined the effects of acetylcholine (ACh) on coronary perfusion pressure (CPP) and force of cardiac contraction (FCC) in isolated rat hearts. Perfusion of hearts with ACh increased both CPP and the FCC, whereas cardiac contraction rate fell. These effects of ACh were abolished by atropine but were not affected by the beta 1-adrenergic antagonist metoprolol. The nonselective beta-adrenergic antagonist propranolol decreased ACh-mediated increase in FCC but did not affect the rise in CPP. Pretreatment of hearts with cyclooxygenase inhibitor indomethacin or thromboxane (Tx) A2-endoperoxide receptor antagonist SQ 29,548 decreased ACh-mediated increase in CPP and FCC, suggesting release of TxA2 in the microvasculature, which may partially account for the increase in CPP and FCC with ACh infusion. In contrast to the effect of indomethacin and SQ 29,548, pretreatment of hearts with endothelium-derived relaxing factor (EDRF) synthetase inhibitor NG-monomethyl-L-arginine (L-NMMA) or guanylate cyclase inhibitor methylene blue potentiated ACh-mediated increase in CPP and attenuated the increase in FCC, suggesting that ACh-mediated increase in CPP is modified by basal EDRF release. Thus the cardiac effects of ACh are related to muscarinic receptor activation, and the release of prostaglandins and EDRF modulates the effects of ACh in isolated rat heart. PMID- 8498553 TI - Blood-to-tissue clearance vs. lymph analysis in determining capillary transport characteristics for albumin in skin. AB - The blood-to-tissue clearance of radioactive albumin and a lymphatic flux analysis were used to evaluate the transport properties of albumin in the canine hindpaw. A prenodal lymphatic was cannulated, and lymph was collected for a 2-h control period. Thereafter venous pressure was elevated between 7 and 31 mmHg. After 2 h of increased venous pressure, the radioactive tracer was given intravenously. During the next 2 h lymph was sampled, and at the end of this time tissue and blood samples were obtained. The experiments showed that, of the tracer filtered in excess of control at increased venous pressure, an estimated 21% was cleared via the lymphatics and 79% was retained in the tissue. As a percentage of total tracer flux at increased venous pressure, 9% (measured) was drained by lymph and 91% was retained in the tissue. Of the fluid filtered in excess of control at increased capillary pressure, 70% (measured) was drained via the lymphatics and 30% was retained in the tissue in the same period. Twice the amount of endogenous albumin filtered across the capillary wall was drained via the lymphatics during the experimental period. The lymphatic washout of endogenous albumin from the interstitium will cause an underestimation of the capillary reflection coefficient and overestimation of the permeability-surface area product. Because of the loss of tracer from the tissue, the opposite occurs when the blood-to-tissue clearance of radioactive albumin is used. PMID- 8498554 TI - Effects of E. coli sepsis and myocardial depressant factor on interval-force relations in dog ventricle. AB - We examined whether depressed left ventricular (LV) contractility during Escherichia coli sepsis in dogs was due to a decrease in the fractional release of calcium from the sarcoplasmic reticulum (SR) or a reduction in calcium content in this organelle. To indirectly assess SR calcium availability in a right ventricular (RV) trabecular muscle preparation, we utilized functional indexes of cellular myocardial calcium metabolism, which included rapid-cooling contracture (RCC), an indicator of SR calcium content, and postrest contraction (PRC), an index of calcium availability from the release compartment of the SR. Measurements were made during steady-state stimulation at 0.5 and 1.5 Hz, during which time rest intervals of 30-240 s were periodically imposed. SR calcium availability was measured in RV trabeculae of dogs subjected to 4 h of E. coli sepsis and was compared with calcium availability measured in nonseptic dogs. We further characterized a filterable cardiodepressant substance (FCS), which has been previously shown to be associated with LV depression in this model, to determine whether it produced changes in calcium metabolism similar to those found in sepsis. The results showed that calcium availability from the SR of septic dogs was not impaired. Furthermore, FCS was found in the 10,000- to 30,000 mol wt fraction of plasma and produced changes in PRC in canine trabeculae that were similar to those produced during sepsis. We conclude that, as assessed by PRC and RCC, SR calcium content and release are not impaired in sepsis. PMID- 8498555 TI - Segmental calculation of left ventricular wall stresses. AB - A procedure for calculating left ventricular wall stresses segmentally was devised. Rectangular coordinates of the wall surfaces as seen in longitudinal section were plotted with the long axis as the x-axis. For each cavity point, a third-order polynomial (cubic spline) was fitted to the point together with several adjacent points on either side of it; the cavity radius (normal to cavity surface) at the point was found algebraically from the spline's coefficients. Each cavity radius was matched with the most symmetrical one from the opposite cavity surface. The point of intersection of the cavity radius with the outer surface was found, and a midwall point was identified from logarithmic means of cavity and outer radial lengths. For each midwall point, a cubic spline was fitted to that point together with several adjacent points on either side of it, and the midwall radius at that point was determined algebraically from the spline's coefficients. Each midwall radius was matched to the most symmetrical one from the opposite midwall. The locus of points at equal radial distances from opposite midwalls forms the axis. The midwall radius of curvature (r theta) orthogonal to the meridian at each point was taken as the radial distance from the midwall to the axis. Midwall meridional radius of curvature (r phi) was calculated from the spline's coefficients. Thickness (h) was calculated from intersections between the midwall radius and the inner and outer surfaces. For each point, meridional tension (T phi) was calculated as T phi = Pr theta/2, and hoop tension (T theta) was calculated as T theta = (Pr theta/2)(2 - r theta/r phi) where P is transmural pressure. Stresses were calculated as tensions divided by thicknesses (sigma phi = T phi/h, sigma theta = T theta/h), or more directly as sigma phi = Pr theta/2h and sigma theta = (Pr theta/2h)(2 - r theta/r phi). This procedure was validated with simple chamber shapes, and it has been applied to left ventricles. PMID- 8498556 TI - Muscle metaboreflex control of vasopressin and renin release. AB - Dynamic exercise causes an increase in circulating blood levels of renin and vasopressin (AVP), yet the afferent mechanisms responsible for release of renin and AVP during exercise are poorly understood. Partial ischemia of active skeletal muscle induces a reflex pressor response, termed the muscle metaboreflex. Does muscle metaboreflex activation induce release of renin and AVP? The muscle metaboreflex was activated in conscious, chronically instrumented dogs during mild treadmill exercise (3.2 km/h, 0% grade) via graded partial occlusion of terminal aortic blood flow. Decreasing hindlimb perfusion to 40% of the control level during exercise significantly increased systemic arterial pressure (SAP) and heart rate (HR) from 103.4 +/- 2.4 to 166.7 +/- 4.2 mmHg and from 111.6 +/- 9.9 to 141.9 +/- 3.9 beats/min, respectively. However, only small nonsignificant changes in arterial plasma renin activity and AVP concentration occurred [control: renin = 0.46 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, AVP = 0.53 +/- 0.17 pg/ml; metaboreflex activation: renin = 0.77 +/- 0.33 ng ANG I.ml 1.h-1, AVP = 1.09 +/- 0.34 pg/ml]. The experiments were repeated after ganglionic blockade (hexamethonium 10 mg/ml and atropine 0.2 mg/ml iv) to attenuate the reflex increase in SAP. In this setting, metaboreflex activation caused SAP to increase from 91.6 +/- 4.3 to only 114.7 +/- 6.8 mmHg and the reflex tachycardia was abolished (153.7 +/- 5.8 to 159.3 +/- 6.1 beats/min, P > 0.05). With the reflex pressor response markedly attenuated, AVP increased from 2.53 +/- 0.81 to 34.38 +/- 6.59 pg/ml with muscle metaboreflex activation, whereas no significant changes in renin activity occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498557 TI - Differential action of plasma and albumin on transcapillary exchange of anionic solute. AB - We tested two hypotheses to account for the reduction in coupling of anionic solute to water flow (solvent drag) in microvessels during perfusion with plasma compared with albumin. Solvent drag is determined by both hydraulic conductivity (Lp) and solute reflection coefficient (sigma). Accordingly, decreased solvent drag during plasma perfusion must be the result of an increase in sigma (hypothesis 1) or reduction of Lp (hypothesis 2) or some combination of both mechanisms. These hypotheses were assessed by measuring Lp, sigma, and diffusive solute permeability (Psd) to the anionic protein alpha-lactalbumin in frog mesenteric exchange microvessels during plasma or albumin perfusion. The solute permeability coefficient to alpha-lactalbumin (Ps alpha-lactalbumin) was lower during exposure to plasma than bovine serum albumin (BSA) [(Ps alpha lactalbumin)plasma/(Ps alpha-lactalbumin)BSA = 0.31 +/- 0.11 (means +/- SE, n = 9)]. Solute reflection coefficient to alpha-lactalbumin (sigma alpha-lactalbumin) was 0.69 +/- 0.02 in plasma and 0.34 +/- 0.03 in BSA (n = 7). Lp was not significantly influenced by perfusate protein composition (Lp plasma/Lp BSA = 1.02 +/- 0.11; n = 20). These data lead to the conclusion that the actions of plasma are to confer charge selectivity for anionic solute and, to a lesser extent, modify the porous pathways of the microvessel wall. Taken together, these results indicate that porous pathways contribute significantly to macromolecular flux in plasma-perfused vessels. PMID- 8498558 TI - Adenosine regulates coronary blood flow during increased work and decreased supply. AB - Adenosine may mediate coronary vasodilation during work-related hyperemia and during ischemia. We tested whether adenosine blockade with 8-p sulfophenyltheophylline (PSPT) prevented dobutamine-induced hyperemia or magnified the reductions in flow due to vasopressin. Control (n = 8) and test (n = 7) dogs received paired infusions of dobutamine (70 micrograms/min iv for 5 min). Test dogs received PSPT (10 mg/kg iv) between doses. In both groups, paired infusions elicited comparable increases in oxygen consumption. However, in test dogs, the hyperemia was reduced significantly. Thus adenosine mediates the hyperemia of dobutamine. Separately, control dogs (n = 9) received vasopressin (0.6 microgram ic over 5 min); test dogs (n = 7) received PSPT before vasopressin. Vasopressin maximally increased coronary resistance by 3 min; effects were gone by 10 min. With PSPT, coronary resistance was increased further and remained high beyond 10 min. Thus adenosine-mediated vasodilation moderates the severity and duration of ischemia. These results indicate the importance of adenosine in mediating coronary flow during increased demand and reduced supply. PMID- 8498559 TI - PAF increases capillary pressure but not vascular permeability in isolated blood perfused canine lungs. AB - We determined the effects of platelet-activating factor (PAF) on pulmonary vascular resistance, lung weight, and microvascular permeability in isolated canine lungs perfused at constant pressure with autologous blood. PAF caused a dose-dependent increase in total pulmonary vascular resistance (Rt) and pulmonary capillary pressure assessed as double-occlusion pressure. PAF (33 micrograms; n = 7) caused a 10-fold increase in Rt and a decrease in precapillary-to postcapillary vascular resistance ratio from 0.97 +/- 0.10 to 0.38 +/- 0.03, suggesting predominant pulmonary venoconstriction. Shortly after PAF, lung weight decreased transiently and then increased, reaching a plateau above baseline (112.5 +/- 1.6%) at 30 min. In lungs perfused in the antidromic direction from the pulmonary vein to the artery (n = 5), PAF (33 micrograms) produced marked precapillary vasoconstriction, consistent with pulmonary venoconstriction, and a remarkable and sustained decrease in lung weight below baseline by 30 min. Vascular permeability, measured 30 min after PAF using the capillary filtration coefficient and isogravimetric capillary pressure, did not change significantly from baseline. Thus we conclude that PAF produces lung weight gain by means of an increase in capillary pressure predominantly due to pulmonary venoconstriction without significant changes in vascular permeability in isolated blood-perfused canine lungs. PMID- 8498560 TI - Effects of acetylcholine on spontaneous contractions in isolated bovine mesenteric lymphatics. AB - The effects of acetylcholine (ACh) on spontaneous contractions in isolated bovine mesenteric lymph vessels were investigated. ACh ranging from 3 x 10(-8) M to 10( 5) M produced dose-dependent negative chronotropic and inotropic effects on the spontaneous contractions. In the lymph vessels without endothelium, ACh at the same concentration range had no significant effect on the spontaneous contractions. Atropine (10(-9) and 10(-8) M) caused a parallel shift to the right of the dose-chronotropic response curve for ACh. The pA2 value of atropine to ACh in the negative chronotropic effect was 8.90 +/- 0.20 (n = 6). Aspirin (10(-5) M) produced no significant inhibition of the ACh-induced negative chronotropic and inotropic effects. NG-monomethyl-L-arginine (L-NMMA; 3 x 10(-5) M) significantly suppressed the ACh-induced negative responses on spontaneous contractions. In the same lymphatic segments, L-arginine (10(-4) M) reversed completely the inhibition by L-NMMA of the ACh-induced responses. These results suggest that low concentrations of ACh produce negative chronotropic and inotropic effects on spontaneous contractions in bovine mesenteric lymphatics and that the responses may be mediated by nitric oxide or its related compound released from the endothelial cells through activation of low-affinity muscarinic receptors. PMID- 8498561 TI - 2-Chloroadenosine prevents phorbol ester-induced depletion of protein kinase C in porcine coronary artery. AB - In this study we investigated the role of the adenosine analogue 2 chloroadenosine (CAD) in the regulation of protein kinase C (PKC) in porcine coronary artery. Arterial rings were contracted with endothelin-1 (ET-1; 10(-10) to 10(-7) M) and phorbol 12,13-dibutyrate (PDBu; 10(-7) M) after incubating them for 1 and 2 days with PDBu (200 nM) in the presence and absence of CAD (10(-4) M). Chronic exposure to PDBu alone attenuated ET-1-induced contractions, while inclusion of CAD during incubation protected against the PDBu-induced blunting of ET-1-induced contraction. Similarly, PDBu (10(-7) M)-induced contraction of the arterial rings was attenuated upon chronic incubation with PDBu, and once again, inclusion of CAD showed an improved response to PDBu-induced contraction when compared with PDBu alone. Incubation with PDBu (200 nM) for 20 min caused the PKC translocation from cytosol to membrane, whereas CAD totally blocked this translocation. Chronic (1 and 2 days) incubation with PDBu caused a substantial depletion of PKC activities in cytosol and membrane. The presence of CAD protected the PDBu-induced depletion of PKC in both cytosol and membrane. To replete PKC, after incubation with the drugs, the arteries were incubated in the absence of drugs for another 2 days. Arteries incubated with PDBu in the presence and absence of CAD recovered significantly in their response to ET-1 as well as PDBu. These results indicate that CAD protects against the PDBu-induced activation and depletion of PKC in porcine coronary artery. PMID- 8498562 TI - A stable L-arginine-dependent relaxing factor released from cytotoxic-activated macrophages. AB - It has been known that cytotoxic-activated macrophages release an unstable vasorelaxing substance, nitric oxide. We have found that a more stable relaxing factor is released from those cells. This factor seems to be synthesized from L arginine. It acts through the activation of soluble guanylate cyclase without affecting membrane potential. It has little charge at nearly neutral pH, and its molecular weight is < 500. PMID- 8498563 TI - Postischemic oxygen radical production varies with duration of ischemia. AB - Oxygen radicals have been implicated in the pathogenesis of myocardial injury. Enhanced chemiluminescence is a sensitive technique for continuous nondestructive measurement of oxygen radical generation. Using an isolated perfused rat heart model, we studied the effect of variable durations of ischemia on oxygen radical generation and postischemic myocardial function. Peak postischemic oxygen radical generation was higher with an intermediate period of ischemia (11.5 min; 528 +/- 53 counts/s) than with either a shorter period (5 min; 328 +/- 21 counts/s) or a prolonged period (40.8 min; 286 +/- 53 counts/s). The magnitude of oxygen radical generation did not correlate with postischemic mechanical function, although it was related to the duration of ischemia with regard to brief and intermediate periods of ischemia (both associated with limited mechanical damage). The increased reperfusion chemiluminescence seen with the intermediate versus the brief ischemic insults can be explained by time-dependent enhancement of the mechanisms present during ischemia that serve to increase oxygen radical generation during reperfusion. In contrast, the longer period of ischemia, resulting in severe mechanical dysfunction, was associated with lower levels of chemiluminescence than observed with an intermediate ischemic duration. This most likely results from the irreversible myocardial injury associated with prolonged ischemia and the consequent inability to generate oxygen radicals. We conclude that, although reperfusion-associated enhancement of myocardial free radical generation may be related to mild to moderate postischemic mechanical dysfunction (stunning), this mechanism may not be of importance in the generation of irreversible reperfusion myocardial injury. PMID- 8498564 TI - Prostanoid synthesis in response to high CO2 in newborn pig brain microvascular endothelial cells. AB - Hypercapnia-induced cerebral vasodilation involves prostanoids in newborn pigs. However, the source of prostanoids has not been determined. The current study was designed to address the hypothesis that piglet cerebral microvascular endothelial cells increase their synthesis of prostanoids in response to high CO2. Microvascular endothelial cells, smooth muscle cells, and glia were isolated and grown in primary culture. They were identified morphologically and by indirect immunofluorescence staining. Cerebral microvascular endothelial cell cultures from newborn pigs produced equal amounts of 6-ketoprostaglandin (PG) F1 alpha (stable hydrolysis product of PGI2), PGE2 and a small amount of PGF2 alpha under basal conditions. Administration of calcium ionophore A23187 to the endothelial cells increased release of all three prostanoids in a dose- and time-dependent manner. Exposure of piglet cerebral microvascular endothelial cells to higher than normal CO2 increased the production of 6-keto-PGF1 alpha and PGE2 but not of PGF2 alpha. The enhanced prostanoid biosynthesis was concentration dependent, peaking at 14% CO2, and was detected during the first 10 min exposure to 14% CO2. Hypercapnia-induced increased synthesis of prostanoids was blocked dose dependently by the simultaneous addition of PGH synthase inhibitor indomethacin. High CO2 did not increase prostanoid production by cerebral microvascular smooth muscle cells or glia, although A23187 enhanced prostanoid formation by both cell types. These data show that high CO2 stimulates prostanoid synthesis by newborn pig cerebral microvascular endothelial cells, which is consistent with an involvement of cerebral vascular endothelium in hypercapnia-induced vasodilation. PMID- 8498565 TI - Measurement of blood pressure and heart rate by telemetry in conscious, unrestrained marmosets. AB - A system is described for the continuous measurement of blood pressure, heart rate, and motor activity by telemetry in conscious marmosets freely moving in their home cages. Consistent diurnal variations in these parameters were observed under standard conditions, although these parameters were sensitive to changes in the environment. Blood pressure values were similar to those measured by nontelemetric methods in conscious, restrained marmosets. However, heart rate was lower, indicating that telemetry is less stressful. The suitability of this system for assessing the effects of blood pressure-lowering drugs was evaluated. An acute or a prolonged treatment with a converting enzyme inhibitor of marmosets maintained on a low-sodium diet induced a fall in blood pressure as previously observed using nontelemetric methods. With telemetry, however, more accurate information on the duration of response and the effects of the treatment on the diurnal rhythms was obtained. These observations demonstrate the advantages of telemetry for evaluating the hemodynamic effects of drug treatments under physiological conditions. PMID- 8498566 TI - Purification and regulation of an AMP-specific cytosolic 5'-nucleotidase from dog heart. AB - The major enzyme responsible for adenosine production during myocardial hypoxia or ischemia is 5'-nucleotidase. We purified an AMP-specific 5'-nucleotidase to homogeneity from the 150,000-g supernatant of dog heart homogenate using phosphocellulose, DEAE-cellulose, and ADP-agarose affinity chromatography. Sodium dodecyl sulfate-poly-acrylamide gel electrophoresis of the purified enzyme yielded a single protein band of 43 kDa. The molecular mass of the holoenzyme, determined by gel filtration and sucrose density-gradient centrifugation, was approximately 166 kDa, suggesting a tetrameric structure. Dog heart cytosolic 5' nucleotidase was active at physiological pH (6.8-7.8) and demonstrated a preference for AMP over IMP as substrate. The enzyme exhibited sigmoidal saturation kinetics, with half-maximal activity at 2.6 mM AMP in the absence of ADP. ADP (0-250 microM) activated cytosolic 5'-nucleotidase by increasing maximal velocity and affinity for AMP. The enzyme was inhibited by 4 mM ATP, but 5' nucleotidase activity increased as [ATP] was reduced. Mg2+ was required for activity, with maximal activation at approximately 3.5 mM free Mg2+. These data suggest that the regulation of AMP-specific cytosolic 5'-nucleotidase by adenine nucleotides and free Mg2+ may be important in the production of adenosine during conditions promoting ATP hydrolysis, such as myocardial hypoxia or ischemia. PMID- 8498567 TI - Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats. AB - To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats. PMID- 8498568 TI - Characterization and mechanisms of H2O2-induced contractions of pulmonary arteries. AB - We studied H2O2-induced contractions of isolated rabbit intrapulmonary arteries mounted in standard tissue baths. All vessels were pretreated with a thromboxane A2/prostaglandin H2 receptor antagonist, SQ 29,548, to block immediate transient contractions to H2O2 and to isolate slowly developing sustained contractions. When exposed to H2O2 (0.1, 0.2, 0.3, 0.6, and 1.0 mM) for 30 min, vessels contracted in (0.1, 0.2, 0.3, 0.6, and 1.0 mM) for 30 min, vessels contracted in a concentration-dependent fashion between 0.1 and 0.3 mM H2O2; contractions at 0.6 and 1.0 mM H2O2 were not significantly different from those at 0.3 mM H2O2. During recovery (90 min) from H2O2 exposures, baseline tension was significantly greater, but active tension (10 microM phenylephrine) was significantly less for vessels previously exposed to 0.6 and 1.0 mM H2O2. Contractions to 0.3 mM H2O2 were not blunted by the following interventions: 1) endothelium rubbing, 2) incubation in Ca(2+)-free 100 microM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) Krebs-Ringer solution, 3) incubation in the Ca(2+)-free solution and depletion of ryanodine (20 microM)-sensitive Ca(2+) stores, or 4) pretreatment with the protein kinase C inhibitor 1-(5 isoquinolinylsulfonyl)-3-methyl-piperazine (20 microM). However, contractions were depressed by approximately 50% when vessels were pretreated with the phospholipase C/serine esterase inhibitor 2-nitro-4-carboxy-phenyl-N,N diphenylcarbamate (50 microM). These results suggest that slow-developing contractions to H2O2 are concentration dependent and may result, in part, from activation of a serine esterase(s) and/or phospholipase C. PMID- 8498569 TI - Subepicardial fiber strain and stress as related to left ventricular pressure and volume. AB - In a mathematical model of the mechanics of the left ventricle (LV) by Arts et al. (1), assuming uniformity of fiber stress (sigma f) and fiber strain (delta epsilon f) in the wall during the ejection phase, fiber stress and fiber strain were related to LV cavity pressure (Plv), LV cavity volume (Vlv) and wall volume (Vw) by the following pair of equations: sigma f = Plv (1 + 3 Vlv/Vw) and delta epsilon f = 1/3 delta ln (1 + 3 Vlv/Vw). The ratio of Vlv to Vw appeared to be the most important geometric parameter, whereas the actual LV shape was of minor importance. The relationships on fiber strain and stress were evaluated experimentally in six anesthetized open-chest dogs during normal and elevated (volume loading) end-diastolic LV pressure. Subepicardial fiber strain was measured simultaneously in 16 adjacent regions of the LV anterior wall, using optical markers that were attached to the epicardial surface and recorded on video. Changes in Vlv were measured by use of four inductive coils sutured to the LV in a tetrahedric configuration. Vw was measured postmortem. During control as well as hypervolemia the following results were found. At the anterior free wall of the LV, the slope of the estimated linear relationship between measured and calculated fiber strain was 1.017 +/- 0.168 (means +/- SD), which is not significantly different from unity. Calculated fiber stress corresponded qualitatively and quantitatively with experimental results reported on isolated cardiac muscle. Calculated subepicardial contractile work per unit of tissue volume was not significantly different from global pump work as normalized to Vw. These findings support the assumption of homogeneity of muscle fiber strain and stress in the left ventricular wall during the ejection phase. Furthermore, average values of fiber stress and strain can be estimated on the basis of measured left ventricular pressure and volume. PMID- 8498570 TI - Effect of carotid sinus stimulation on resistance and critical closing pressure of the canine hindlimb. AB - Sympathetically mediated changes in blood pressure are thought to occur through changes in arterial resistance (Ra). To test whether the critical closing pressure (Pcrit) could also play a role, we pump-perfused the vascularly isolated canine hindlimb at constant flow. Carotid sinuses were isolated and both vagus nerves cut. Carotid sinus (Pcar), arterial, perfusion (Pper), and venous (Pv) pressures and flow to the hindlimb (Q, electromagnetic flow probe) were measured. By decreasing pump flow to zero over time periods of 1-10 s and measuring the pressure at zero-flow, it was possible to estimate arterial compliance and Pcrit. Ra was calculated as (Pper - Pcrit)/Q. Venous resistance was calculated as (Pel - Pv)/Q, where Pel is the pressure in the compliant region obtained by the double occlusion technique. Raising Pcar from 115 +/- 7 to 203 +/- 10 mmHg (n = 6) decreased Pcrit from 49.7 +/- 4.3 to 25.9 +/- 2.6 mmHg and Ra from 10.7 +/- 1.2 to 6.8 +/- 0.9 mmHg.min.100 g-1.ml-1 (P < 0.05). Lowering Pcar from 119 +/- 6 to 71 +/- 6 mmHg (n = 6) increased Pcrit from 37.0 +/- 3.3 to 61.0 +/- 8.5 mmHg and Ra from 10.0 +/- 1.6 to 14.0 +/- 2.4 mmHg.min.100 g.ml-1 (P < 0.05). Arterial compliance increased when Pcar was raised (P < 0.05) and decreased when Pcar was decreased (P < 0.1). Venous resistance did not change when Pcar was altered. In conclusion, changes in carotid sinus stimulation alters blood flow to the hindlimb through changes in both Pcrit and Ra. PMID- 8498571 TI - Bradykinin-induced elevations of hydraulic conductivity display spatial and temporal variations in frog capillaries. AB - Bradykinin, a vasodilator, increases permeability to macromolecules in postcapillary venules. Recent studies indicate that vasodilators elevate water flux from frog mesenteric capillaries. Thus we hypothesized that bradykinin would also increase transcapillary water flux. Arteriolar (ac), true (tc), and venular (vc) capillaries were identified within the microvascular network of frog mesentery. Each capillary was cannulated in situ and perfused with control (frog Ringer and 10 mg/ml bovine serum albumin) and then bradykinin test (10(-7) M) solutions. Hydraulic conductivity (Lp) increased across the network (1.8, 5.3, and 11.0 x 10(-7) cm.s-1.cmH2O-1 for ac, tc, and vc, respectively). Bradykinin test Lp normalized to control (LpBKN/LPC) was elevated threefold (n = 37). Lp for ac (n = 12) was elevated 3.5-fold and oscillated with time. Lp for tc (n = 13) increased fivefold within the first 5 min of exposure and then dropped. Lp for vc (n = 12) was not different from control. Location- and time-dependent responses of Lp indicate that capillaries forming microvascular networks have individual responses to bradykinin. PMID- 8498572 TI - Polymorphonuclear leukocyte-derived O2-reactive species activate primed platelets in human whole blood. AB - The activation of human platelets by polymorphonuclear leukocytes (PMN) was investigated in human whole blood challenged with "priming" concentrations of arachidonic acid or collagen in the presence or absence of N-formyl-Met-Leu-Phe (FMLP), a selective activator of PMN. With the use of arachidonic acid or collagen alone at priming concentrations or FMLP alone, no platelet response was observed. In contrast, FMLP in combination with arachidonic acid or collagen caused irreversible platelet aggregation with thromboxane A2 production. Platelet response to FMLP-activated PMN was enhanced by superoxide dismutase and blocked by catalase or the NADPH oxidase inhibitor diphenyliodonium, suggesting a role for the O2-.-H2O2 system in this cellular interaction. This was corroborated by experiments with exogenously added H2O2, which mimicked FMLP effects in the activation of primed platelets in whole blood. The present investigation indicates that platelets primed with minute amounts of arachidonic acid or collagen can be activated, in human whole blood, by oxygen-reactive species released by PMN. PMID- 8498573 TI - CaATPase content is lower in cardiac sarcoplasmic reticulum isolated from old rats. AB - The rate of oxalate-facilitated ATP-dependent calcium uptake by the calcium pump, calcium adenosinetriphosphatase (CaATPase), is 30-40% slower in the sarcoplasmic reticulum (SR) isolated from the hearts of senescent Fischer 344 male rats. To determine the underlying mechanism, cardiac SR was isolated from 11- to 12-mo-old (adult) and 22- to 24-mo-old (senescent) male Fischer 344 rats. The yield of SR and contamination by other membrane organelles were similar between the groups. The rate of calcium uptake by the homogenate and isolated SR was 28-44% slower (P < 0.05) in the senescent group. In the isolated SR the calculated maximal velocity (Vmax) of CaATPase activity as a function of varying concentrations of ATP or calcium was 20-30% lower (P < 0.05) in the senescent group; however, the affinities for both calcium and ATP of CaATPase activity were unaltered. The lower Vmax was matched by a decreased (P < 0.05) content of calcium-dependent phosphoenzyme (EP) in the SR isolated from the senescent rats. Thus the ratio of enzyme activity to phosphoenzyme content (Vmax/EP) was similar between the groups. The immunoreactive CaATPase protein was 22 +/- 2% lower in the SR from the senescent rats. Taken together the data indicate that the major mechanism underlying the slower calcium transport by cardiac SR isolated from old rats is a lower content of the CaATPase protein. PMID- 8498574 TI - Cardiocyte contractile performance in experimental biventricular volume-overload hypertrophy. AB - Previous studies have shown that the right ventricle (RV) appears to tolerate volume overloading better than does the left ventricle (LV). To determine whether this dichotomous response is due to intrinsic differences in the contractile performance of volume hypertrophied RV vs. LV cardiac muscle cells, or cardiocytes, we characterized the contractile performance of cardiocytes isolated from an experimental feline model of biventricular volume overload (n = 7 cats), wherein a peripheral arteriovenous fistula (AVF) produced an identical duration and degree of volume overload for both ventricles; sham-operated cats served as the appropriate controls (n = 7). Cardiocyte contractile function was defined by laser diffraction measurement of sarcomere motion. For the AVF cats, there was a 2.4-fold increase in cardiac output, a significant increase in the RV and LV weight-to-body weight ratios, and a significant increase in cell surface area for the RV and LV cardiocytes. Despite this, cardiocyte contractile function in the AVF cats was entirely normal. Thus there was no significant difference between RV and LV cardiocytes from control cats in the extent or velocity of sarcomere shortening either in 1 cP superfusate or in higher viscosity superfusates, and comparison of RV and LV cells from the AVF cats to those from sham-operated cats again revealed no significant differences. Furthermore, cardiocyte relengthening properties showed no significant differences between AVF and control groups. In summary, this study shows that contractile dysfunction is not an inherent property of either RV or LV cardiac muscle cells hypertrophying in response to substantial volume overloading when preload is increased but afterload is normal. PMID- 8498575 TI - Stopped-flow epicardial lymph pressure is affected by left ventricular pressure in anesthetized goats. AB - We measured epicardial lymph pressure (Plymph) in the anesthetized goat (n = 5 goats). To study the transmission of systolic left ventricular pressure (PLV) to Plymph, the effect of an increase in PLV caused by clamping of the descending aorta on Plymph was evaluated. Peak systolic PLV was 131 +/- 4 (+/- SE) mmHg during control (43 beats) and 188 +/- 4 mmHg when elevated due to aortic clamping (157 beats). Peak systolic Plymph was 24.8 +/- 1.0 and 34.8 +/- 1.1 mmHg during control and elevated PLV, respectively. In the first beat of elevated PLV, peak Plymph did not change, although the pressure waveform did. In the subsequent beats, Plymph increased proportionally with increased PLV. When PLV was decreased back to control, Plymph also decreased but did not reach control level until after three beats. The relationship between normalized Plymph and normalized PLV is given by Plymph = 0.70 x PLV + 0.09. The results show that PLV does affect Plymph in a normal beating heart. PMID- 8498576 TI - Differential sensitization of cardiac actions of adenosine in rats after chronic theophylline treatment. AB - To determine the effect of chronic adenosine receptor blockade on atrial responsiveness, we administered theophylline to rats in their drinking water (0.6 mg/ml) for 2 wk. Inotropic and chronotropic responses to the adenosine receptor agonists N6-cyclopentyladenosine (CPA) and 5'-(N-ethylcarboxamido)-adenosine (NECA) were then measured in isolated atria from treated and control animals. The indirect (antiadrenergic) actions of CPA and NECA on force and rate, measured during beta-adrenergic receptor stimulation by isoproterenol, were markedly sensitized (2- to 10-fold reductions in the agonist concentration needed to obtain a half-maximal response) after theophylline. The sensitization was homologous because inotropic and chronotropic responses to carbachol were not affected by theophylline. The direct negative inotropic and chronotropic actions of CPA and NECA, measured without concomitant beta-adrenergic stimulation, were not sensitized after theophylline. The number of atrial A1-receptors, measured by antagonist radioligand binding (maximum specific binding at saturation), was increased by 22% in theophylline-treated rats [66.2 +/- 3.4 vs. 54.3 +/- 1.9 (control) fmol/mg protein, P < 0.05]. Competition binding indicated that the fraction of coupled (high-affinity) receptors was unchanged. The number of ventricular A1-receptors was increased to a similar extent without any change in coupling. Thus chronic dietary theophylline upregulated cardiac A1-adenosine receptors without changing coupling state or affinity and sensitized rat atria to the indirect, antiadrenergic, inhibitory inotropic and chronotropic actions of adenosine receptor agonists. PMID- 8498577 TI - Smooth muscle myosin heavy chains combine to form three native myosin isoforms. AB - Two smooth muscle myosin heavy chains (MHC; SM1 and SM2) of approximately 204 and 200 kDa exist in smooth muscle cells and can be visualized on reducing sodium dodecyl sulfate (SDS)-polyacrylamide gels. Chymotryptic digestion of the native myosin molecule results in two fragments: heavy meromyosin (HMM) and light meromyosin (LMM). LMM is the alpha-helical coiled-coil carboxy terminal half of the molecule containing the difference peptide between SM1 and SM2. Electrophoresis of the LMM fragments on a reducing SDS-polyacrylamide gel resolves two subunits from the two MHC [LM1 from SM1 (approximately 100 kDa) and LM2 from SM2 (approximately 95 kDa), where LM1 and LM2 are LMM from SM1 and SM2, respectively]. CuCl2 oxidation of the LMM fragment forms intramolecular disulfide bonds between adjacent cysteines on the two LMM fragments. When the native LMM is oxidized with CuCl2 and run on a nonreducing SDS-polyacrylamide gel, three bands are observed, which migrate at approximately 195, 190, and 185 kDa (bands 1, 2, and 3). Excision of these bands and electrophoresis on a reducing SDS polyacrylamide gel show their subunit composition. Band 1 is composed solely of LM1. Band 2 is composed of an equal ratio of LM1 and LM2, and band 3 is composed solely of LM2. Using a variety of biochemical procedures, along with nonreducing SDS-polyacrylamide gels, we interpret these results to indicate that there are three smooth muscle myosin isoforms that result from the various combinations of the two smooth muscle MHC (SM1 homodimer, SM1-SM2 heterodimer, and SM2 homodimer). PMID- 8498578 TI - Potentiated state contractions in isolated hearts: effects of ischemia and reperfusion. AB - To investigate mechanisms underlying the contractile dysfunction during myocardial "stunning," potentiated contractions were studied in Langendorff perfused rabbit hearts paced at 2.5 Hz. Isovolumetric left ventricular pressure (LVP) and the first derivative of LVP (dP/dt) were measured via a balloon. Potentiated contractions, elicited after 3 s of rest (postrest potentiation, PRP) or with paired pulses (paired-pulse potentiation, PPP) were first characterized in nonischemic conditions. Exposure to 5 nM ryanodine changed PRP into postrest depression [control, 134 +/- 1.7% (SE); ryanodine, 65 +/- 3.4%; n = 5] but did not decrease PPP (control, 125 +/- 7.2%; ryanodine, 141 +/- 14.5%). When sarcolemmal Ca2+ influx was decreased by 0.2-2 microM verapamil, PRP increased (control, 136 +/- 3.7%; 1 microM verapamil, 214 +/- 23.8%; n = 5), whereas PPP was maintained (control, 134 +/- 8.0%; 1 microM verapamil, 154 +/- 11.5%). During ischemia, both PRP and PPP were increased above preischemic values (from 128 +/- 1.9 to 355 +/- 60.4% and from 122 +/- 5.4 to 313 +/- 37.4%, respectively, n = 5). Changes of potentiation of dP/dt were qualitatively similar to those of LVP. On reperfusion, rest potentiation transiently decreased (PRP of dP/dt: 127 +/- 6% preischemia vs. 112 +/- 3% at 2 min postischemia; n = 6). However, PPP increased during the first 20 min of reperfusion (PPP of dP/dt: 184 +/- 22% preischemia vs. 236 +/- 34% postischemia; n = 6). This transient depression of PRP during reperfusion suggests an impairment of sarcoplasmic reticulum function in stunned myocardium, at least during the early phase of reperfusion. PMID- 8498579 TI - Area postrema and aortic or vagal afferents converge to excite cells in nucleus tractus solitarius. AB - Area postrema neurons enhance baroreflex function, perhaps by augmenting baroreceptor afferent processing in the nucleus tractus solitarius (NTS). If so, NTS neurons should receive convergent excitatory inputs from area postrema neurons and baroreceptors. The aims of this study were to record extracellular activity of NTS neurons to determine whether 1) area postrema and aortic baroreceptor afferents converged in NTS, 2) area postrema and vagal afferents converged in NTS, and 3) the convergent inputs were facilitative. Studies were performed in pentobarbital sodium- or alpha-chloralose-anesthetized rabbits. Forty-six of 194 NTS neurons received inputs from the area postrema and aortic depressor nerve. Twelve of the 23 inputs showed facilitative summation; unit response rate evoked by paired inputs (79%) doubled the predicted (calculated) response rate for simple addition (37%). Fifty-eight of 114 NTS neurons received excitatory inputs from the area postrema and vagus. Eleven of the 13 inputs showed facilitative summation; unit response to paired inputs (87%) doubled the predicted response (44%). Area postrema neurons may augment the processing of aortic and vagal inputs by NTS neurons and, hence, enhance the reflex output of these afferent pathways. PMID- 8498580 TI - Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel. AB - Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U 74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498581 TI - Identification of SV40 large T-antigen-associated proteins in cardiomyocytes from transgenic mice. AB - A cell line derived from transgenic mice expressing the SV40 large T-antigen oncogene in the heart was used to identify cardiomyocyte targets for T-antigen binding. A novel protein of molecular mass of 193 kDa was identified as an associated protein by virtue of its ability to be co-immunoprecipitated with multiple anti-T-antigen antibodies. Two previously described proteins, p120 and p53, were also observed to complex with T-antigen in transformed cardiomyocytes. In addition, several proteins that cross-reacted with either anti-T-antigen or anti-p53 antibodies were identified. Two of these proteins, of apparent molecular masses of 250 and 110 kDa, were only observed in cardiomyocytes. Expression of a third cross-reacting protein of a molecular mass of 180 kDa appeared to be dependent on the growth status of the cells. These proteins may be important constituents of the cardiomyocyte cell cycle, as well as potential cellular targets for myocardial regeneration. PMID- 8498582 TI - Vasopressin contributes to the cardiovascular response to dynamic exercise. AB - Vasopressin is a powerful vasoconstrictor that is released into the systemic circulation during exercise. We tested the hypothesis that this peptide contributes to the cardiovascular response during treadmill exercise in the pig. Seventeen miniswine were instrumented with epicardial electrocardiogram leads, left atrial and aortic catheters, and a left ventricular pressure transducer for measurement of heart rate (HR), regional blood flow, arterial blood pressure (MAP), and myocardial contractility [first derivative of left ventricular pressure (dP/dt) at 40 mmHg developed pressure] at rest and during exercise. At a work intensity of 80% of each animal's maximal HR reserve, exercise-induced increases in MAP, HR, dP/dt at 40 mmHg developed pressure, and cardiac output were measured. On a separate day, the workload performed by each animal was replicated in the presence of selective vasopressin V1-receptor inhibition using the specific V1 antagonist, [d(CH2)5Tyr(Me)]arginine vasopressin (10-14 micrograms/kg iv). During exercise, MAP was lower (96 +/- 3 vs. 104 +/- 2 mmHg) and cardiac output was higher (13.5 +/- 0.6 vs. 12.6 +/- 1.0 l/min) in the presence of V1-receptor blockade than during unblocked conditions, respectively. Furthermore, we observed an attenuation of exercise-induced decreases in blood flow to the colon. Increases in vascular resistance in the stomach, small intestine, colon, and pancreas also were diminished by V1-receptor inhibition. However, HR and myocardial contractile responses to exercise were not affected. These results suggest that vasopressin contributes to increases in MAP and to the redistribution of cardiac output during dynamic exercise in the miniswine. PMID- 8498583 TI - Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury. AB - To test the possible involvement of superoxide radicals in the pathogenesis of reperfusion injury, we synthesized a superoxide dismutase (SOD) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalently linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protective effects of SM-SOD on regional cerebral blood flow, intracranial pressure, cardiac index, vascular permeability, and neurological outcome were investigated using a model of global brain ischemia in dogs. Intra-arterial injection of SM-SOD (10 mg/kg) just before reperfusion increased reactive hyperemia (SM-SOD, 160 +/- 36 ml.100 g-1.min-1, means +/- SD, n = 6; control, 100 +/- 34 ml.100 g-1.min-1, n = 6, P = 0.015), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 +/- 14 ml.100 g-1.min-1; control 17 +/- 6 ml.100 g-1.min-1, P = 0.003), vascular permeability, and neurological outcome without affecting the cardiac index. These results indicate that superoxide radicals and/or their metabolite(s) might play a critical role in the pathogenesis of reperfusion injury in the brain. PMID- 8498584 TI - Nonlinear heart model predicts range of heart rates for 2:1 swinging in pericardial effusion. AB - We analyze two mathematical models of Rigney and Goldberger (14) of heart swinging in large pericardial effusions. Both models represent the torques due to the outflow of blood from the heart. The first assumes that the duration of systole does not vary with heart rate (in beats/min), whereas the second assumes that it varies linearly with heart rate. We examine the motion of the heart for heart rates between 50 and 200 and for a range of initial positions and velocities. Both models predict that the heart swings once every other beat (2:1 swinging, giving rise to electrical alternans) in a discrete range of heart rates and swings once per beat otherwise; both models explain the appearance and disappearance of 2:1 swinging mathematically. The first model predicts a rate range from 105 to 116 for the occurrence of 2:1 swinging. The second model predicts the same qualitative behavior but with 2:1 swinging occurring at heart rates between 88 and 119, which agrees well with published clinical data showing 2:1 swinging at heart rates between 90 and 144. We describe an analysis program for ordinary differential equations that analyzed the models quickly and automatically. PMID- 8498585 TI - Albumin fraction and measurement of total protein concentration. AB - The standard curve of a typical colorimetric assay for total protein is often nonlinear and dependent on the albumin fraction of the protein standard. We developed a simple mathematical transformation to make the standard curve linear and a computational method to correct for differences in albumin concentrations among the samples. This method uses data from total protein assays on two sets of standards (albumin and gamma globulin) and provides accurate measures of total protein over the full range of albumin fractions. Comparison of this two-standard method with the a method that uses only albumin as a standard shows that this method prevents physiologically significant overestimations in total protein concentration and calculated protein osmotic pressure differences in the lungs. PMID- 8498586 TI - Long-term survival of AT-1 cardiomyocyte grafts in syngeneic myocardium. AB - The long-term viability of cardiomyocyte grafts in the adult myocardium was tested. AT-1 cardiomyocytes, a differentiated tumor line derived from transgenic mice expressing an atrial natriuretic factor-simian virus 40 T antigen fusion gene, were grafted directly into the myocardium of syngeneic animals. Viable grafts were detected as long as 4 mo postimplantation. Thymidine uptake studies suggested that the grafted cardiomyocytes retained mitotic activity. The presence of AT-1 cardiomyocyte grafts and the associated myocardial remodeling were not accompanied by overt cardiac arrhythmia. Electron microscopic analyses showed that the majority of the grafts were juxtaposed directly to the host myocardium and were not encapsulated. This study indicates that the myocardium can serve as a stable platform for cells that have been manipulated in vitro and suggests that cardiomyocyte grafts may provide a useful means for the local delivery of recombinant molecules to the heart. The long-term survival of the AT-1 cardiomyocytes in the heart also raises the possibility that similar grafting approaches may be used to replace diseased myocardium. PMID- 8498587 TI - Evidence that heterogeneity of cerebral blood flow does not involve vascular recruitment. AB - Recent studies indicate that blood flow to cerebral cortex is not homogeneous but may vary both spatially and temporally. In addition, some investigators have reported that capillaries and arterioles can be recruited to increase cerebral blood flow, an issue that is extremely controversial. The goal of this study was to determine whether recruitment of cerebral blood vessels is an important mechanism in spatial and temporal heterogeneity of cerebral blood flow. In seven anesthetized ventilated rats, different fluorescent tracers were injected 45 and 10 s before decapitation. In addition, [14C]iodoantipyrine also was injected 10 s before decapitation. After the brains were sectioned, fields in the cerebral cortex were examined microscopically for fluorescence and processed for measurement of cerebral blood flow with techniques of quantitative autoradiography and image analysis. With examination of 24 +/- 2 (SE) points in cerebral cortex of each rat, similar numbers of small blood vessels (< or = 10 microns) were counted that contained fluorescent tracers injected 45 and 10 s before decapitation (346 +/- 48 and 355 +/- 42 vessels/mm2, respectively; P > 0.05). Large blood vessels (20-60 microns; 73 +/- 6 vessels in each rat) contained both fluorescent tracers. In addition, adjacent regions of high and low blood flow contained similar numbers of small and large vessels. Our findings indicate that vascular recruitment is not an important mechanism in temporal or spatial heterogeneity of cerebral blood flow. PMID- 8498588 TI - Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide. AB - The purpose of this study was to determine whether glucocorticoids exert inhibitory feedback on lipopolysaccharide (LPS)-induced fever, stress-induced fever (exposure to an open field), and plasma concentrations of interleukin-6 (IL 6)-like and tumor necrosis factor-alpha (TNF)-like activity in biotelemetered rats. Injections of LPS (50 micrograms/kg) or exposure to an open field (30 min) led to significantly higher fevers in adrenalectomized (ADX) rats than in sham ADX rats. To test the hypothesis that higher fevers were specifically the result of an absence of glucocorticoids, the glucocorticoid antagonist RU 38486 (20 mg/kg) was administered orally to rats with intact adrenal glands. The RU 38486 treated rats had higher plasma concentrations of IL-6-like activity and developed significantly higher fevers than did vehicle-treated rats. Rats injected intracerebroventricularly with 10 ng RU 38486 also developed higher fevers. Other ADX animals were implanted subcutaneously with replacement corticosterone pellets before exposure to an open field or injection with LPS. In response to an open field or injection with LPS, ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in stressed animals (100 mg pellets) developed fevers that were significantly lower than those observed in ADX rats given placebo pellets, but that were not different from fevers in sham ADX rats given placebo pellets. ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in unstressed animals (25-mg pellets) developed fevers that were significantly higher than those observed in sham-ADX rats given placebo pellets, but that were not different from fevers in ADX rats given placebo pellets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498589 TI - Rapid changes in metabolic cold defense and GDP binding to brown adipose tissue mitochondria of rat pups. AB - To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled. PMID- 8498590 TI - Arterial pulse pressure and vasopressin release in humans during lower body negative pressure. AB - The hypothesis was tested that narrowing of arterial pulse pressure (PP) is a determinant of arginine vasopressin (AVP) release in humans. Six normal males completed a two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg, respectively, for 10 min each. None of these subjects experienced presyncopal symptoms. Arterial plasma AVP and plasma renin activity (PRA) (at 2 min intervals) only increased subsequent to a decrease in PP (invasive brachial arterial measurements) and stroke volume (ultrasound Doppler technique, n = 4). Simultaneously, mean arterial pressure did not change. A selective decrease in central venous pressure and left atrial diameter (echocardiography, n = 4) at LBNP of -20 mmHg did not affect AVP or PRA, whereas arterial plasma norepinephrine increased (n = 4). During LBNP, significant (P < 0.05) intraindividual linear correlations were observed between log(AVP) and PP in four of the subjects with r values from -0.75 to -0.99 and between log(PRA) and PP in all six subjects with r values from -0.89 to -0.98. In conclusion, these results are in compliance with the hypothesis that narrowing of PP in humans during central hypovolemia is a determinant of AVP and renin release. PMID- 8498591 TI - Renal and systemic adaptation to sodium restriction in aging rats. AB - The influence of age on the systemic and renal adaptation to dietary sodium restriction was assessed in 10-, 20-, and 30-mo-old female WAG/Rij rats. In control conditions, mean arterial pressure (MAP) was similar in all rats and plasma renin activity (PRA) was lower in 30- than in 10- and 20-mo-old rats (2.5 +/- 0.6, 5.1 +/- 0.4, and 3.9 +/- 1.0 ng ANG I.ml-1.h-1, respectively). Dietary sodium restriction was associated with a reduction in MAP in 30-mo-old rats, whereas no change occurred in 10- and 20-mo-old rats. Impairment in the early (days 1-6) renal adaptation to salt restriction was observed in 30- compared with 10- and 20-mo-old rats (6-day cumulative sodium excretion of 728 +/- 139, 437 +/- 53, and 478 +/- 37 mumol, respectively). During the 7- to 12-day period, MAP stabilized in the oldest rats and cumulative sodium excretion became similar to that of other age groups. The early increase in PRA and urinary aldosterone excretion observed in 10- and 20-mo-old rats was consistently blunted in 30-mo old rats. These findings suggest that the delayed response of the renin angiotensin-aldosterone system has a major role in the impaired renal and systemic adaptation to dietary sodium removal in senescent rats. PMID- 8498592 TI - A mathematical model of oscillatory insulin secretion. AB - Insulin is secreted in sustained oscillatory fashion from isolated islets of Langerhans. This finding has led to the assumption of an underlying synchronizing process that coordinates insulin oscillations. This assumption was tested by developing a mathematical model of oscillatory insulin secretion in which we included degree of synchrony as a parameter. We first evaluated insulin oscillations in perifused isolated rat islets, using spectral analysis to determine their regularity and frequency. A parsimonious mathematical model was developed to account for these characteristics. The model postulates a group of secretory units discharging at discrete intervals with the same underlying period. Variation from two sources, phase differences between units (synchrony) and regularity within units, is introduced by adding two normally distributed random variables with standard deviations (Sg and Si, respectively) to the secretory period. Sets of 100 simulations for different values of Sg and Si were run. Results of the simulations suggest that the system tolerates a relatively large degree of asynchrony yet still demonstrates regularity of oscillations on spectral analysis. Comparison with perifusion data suggests that a moderate degree of asynchrony between islets can best account for the pattern of insulin oscillations observed. This model provides a theoretical basis for the study of mechanisms for insulin oscillations. PMID- 8498593 TI - Cholecystokinin octapeptide decreases food intake in white-crowned sparrows. AB - White-crowned sparrows maintained on short days (9:15-h light-dark cycle) were peripherally injected with 1.0, 4.0, and 16 micrograms/kg ip of cholecystokinin octapeptide (CCK-8). Meal size over the subsequent 30 min was significantly depressed in a dose-dependent fashion. Water intake was not affected. The anorexic effect caused by 4.0 micrograms/kg was attenuated by 100 micrograms/kg of the type-A CCK receptor antagonist MK-329 but not by 300 micrograms/kg of the type-B CCK receptor antagonist L 365,260, suggesting that CCK-induced suppression of food intake in this species is mediated by a CCK-A receptor. Administration of both CCK-A and CCK-B receptor antagonists alone resulted in no change in meal size. These experiments suggest that white-crowned sparrows, when weight stable, respond to CCK-8 in a manner comparable with several mammalian species. PMID- 8498594 TI - The 10-Hz sympathetic rhythm is dependent on raphe and rostral ventrolateral medullary neurons. AB - We studied the effects of brain stem and spinal lesions on the 10-Hz rhythms in left and right inferior cardiac sympathetic nerve discharge (SND) of baroreceptor denervated, decerebrate cats. Unilateral medullary lesions [parasagittal section 1.5 mm lateral to midline, radiofrequency lesion of the rostral ventrolateral medulla (RVLM), or chemical inactivation (muscimol) of the RVLM] dramatically reduced the 10-Hz rhythmic discharges in the two nerves. Power in the 10-Hz band of ipsilateral inferior cardiac SND was reduced more than that in contralateral SND. In contrast, bilateral parasagittal medullary sections or microinjection of muscimol into the medullary raphe uniformly reduced the 10-Hz rhythmic discharges of both nerves. Unlike unilateral medullary lesions, rostral pontine or cervical spinal hemisection reduced the 10-Hz discharges of only the ipsilateral inferior cardiac nerve. The chemical inactivation experiments demonstrate that the 10-Hz rhythm in SND is dependent on medullary raphe and RVLM neurons. Moreover the experiments with unilateral lesions demonstrate a mutually facilitatory interaction of medullary circuits that are responsible for the 10-Hz rhythmic discharges in sympathetic nerves located on opposite sides of the body. PMID- 8498595 TI - Calcium sensitivity of skinned ferret EDL, soleus, and cremaster fibers. AB - The properties of the contractile system at different times of the year in the ferret extensor digitorum longus (EDL), soleus and cremaster muscles were examined by using chemically skinned (Triton X-100) preparations. The results show clear differences in calcium sensitivity between these skeletal muscles. The apparent calcium threshold for activation was lower in soleus than in EDL, while calcium concentrations ([Ca2+]) required to obtain the half-maximal tension, expressed as pCa50 (-log[Ca2+]), was lower in EDL than in soleus muscle. In fact, pCa50 obtained in fast and slow fibers by fitting the experimental data points by a modified Hill equation was 5.92 +/- 0.02 (n = 9) and 6.09 +/- 0.03 (n = 11) respectively. So EDL appears to be a typical fast-twitch muscle and soleus a typical slow-twitch muscle. Adult ferret cremaster muscle was composed of two types of fibers during the quiescent period similar to EDL and soleus, and only one type that was intermediate between EDL and soleus in the breeding period, as assessed by pCa50 values. These annual modifications in calcium activation of adult ferret cremaster muscle could be related to changes in the function of these muscles and may be correlated with seasonal variations of sexual activity. PMID- 8498596 TI - On the suppression of food intake in experimental models of colitis in the rat. AB - We measured daily food intake and body weight in rats before and after the induction of colitis by intrarectal administration of either 2,4,6 trinitrobenzenesulfonic acid in ethyl alcohol (TNBE) or 4% acetic acid (AA). Administration of TNBE or AA induced inflammation in the distal colon, which was reflected by a significant increase in myeloperoxidase (MPO) activity in the colon. On days 1, 2, and 3 after induction of colitis by TNBE, food intake fell by 80, 70, and 50%, respectively, compared with pretreatment values; food intake returned to normal by day 4. Body weight fell within 24 h after induction of colitis and remained 10% less than control for at least 5 days. Colitis induced by AA produced a similar pattern and degree of decreased food intake and weight loss. Treatment with the 5'-lipoxygenase inhibitor MK-886 significantly reduced concentrations of leukotriene B4 in the colon of TNBE-treated rats but did not affect food intake. In contrast, the cyclooxygenase inhibitor indomethacin decreased prostaglandin E2 concentrations in the colon but also attenuated the suppression of feeding by 52 and 64% on the first 2 days after induction of colitis by TNBE. These results identify a specific prostaglandin-mediated suppression of feeding in the rat with acute colitis induced by TNBE and illustrate the utility of this model for studying mechanisms underlying anorexia associated with inflammation of the gastrointestinal tract. PMID- 8498597 TI - Effects of drinking on thirst and vasopressin in dehydrated elderly men. AB - Inhibition of dehydration-induced arginine vasopressin (AVP) secretion and thirst depends on removal of osmotic and hemodynamic stimuli as well as on preabsorptive oropharyngeal factors that reduce thirst and AVP secretion on drinking before correction of the water deficits. Plasma atrial natriuretic peptide (ANP) levels may also change with drinking. Therefore, the thirst and plasma responses to oral water loads (10 ml/kg) in 10 healthy old (64-76 yr) and young (20-32 yr) 24-h water-deprived men were investigated. After 24-h water deprivation plasma sodium, osmolality, and AVP were increased similarly in both groups (P < 0.001). Plasma ANP levels fell after dehydration similarly in both groups (P < 0.05) but were always higher in the older group (P < 0.05). However, although thirst increased in both groups (P < 0.05), this was significantly less in the elderly (P < 0.05). After the water load, thirst was reduced in both groups throughout the study (P < 0.05). However, plasma AVP fell immediately after drinking only in the young group and rose to postdeprivation levels after 15 min. Plasma AVP was not different from postdeprivation throughout in the old group and after 15 min in the young group presumably because the water load was insufficient to replace their water deficits. In the young group only, plasma ANP rose to 182 +/- 43% of postdeprivation levels at 3 min after drinking (P < 0.05). These results demonstrate reduced oropharyngeal inhibition of AVP secretion after drinking in healthy elderly men but maintained inhibition of thirst. PMID- 8498598 TI - Intracellular compartmentation of organic anions within renal cells. AB - Epifluorescence microscopy and video-image analysis were used to measure the distribution of the monovalent organic anion fluorescein (FL) within the cells of three organic anion-secreting renal epithelia: crab urinary bladder (a proximal tubule analogue), opossum kidney (OK) cells in culture, and intact teleost proximal tubules. In all three preparations the intracellular FL distribution was nonuniform. Two distinct intracellular compartments were detected, one being diffuse and cytoplasmic and the other punctate. With low FL concentrations in the medium (1 microM and below) dye accumulation in the punctate compartment exceeded that of the cytoplasm. In crab bladder epithelium FL uptake into both compartments was inhibited by external probenecid, p-aminohippurate (PAH), and LiCl and stimulated by 10-50 microM external glutarate, suggesting that the punctate compartment loaded by a two-step mechanism: transport into the cytoplasm at the basolateral membrane, followed by accumulation at specific intracellular sites. Experiments in which FL was microinjected into OK cells directly demonstrated movement of FL from the cytoplasmic to the punctate compartment. Accumulation in the latter was specific, i.e., inhibitable by coinjected PAH and probenecid, and energy dependent. Together, these findings indicate that during secretion organic anions are sequestered within renal cells. The role of sequestration in overall transport remains to be determined. PMID- 8498599 TI - Angiotensin II-induced endothelium-dependent relaxation of fowl aorta. AB - In the domestic fowl, angiotensin II (ANG II) decreases blood pressure in vivo and causes endothelium-dependent relaxation of aortic smooth muscles in vitro. To characterize ANG II-induced vasorelaxation, we compared endothelium-dependent vasodilatory effects of [Asp1,Val5]-ANG II (fowl ANG II) and acetylcholine (ACh) with the endothelium-independent vasorelaxing effect of sodium nitroprusside (SNP) on isometric tension of fowl aortic rings. Hemoglobin (Hb), gossypol, and N omega-nitro-L-arginine methyl ester (L-NAME), inhibitors for endothelium-derived relaxing factor (EDRF) in mammalian blood vessels, partially inhibited vasorelaxation induced by ANG II and ACh in fowl. Hb also markedly attenuated SNP induced vasorelaxation, but not 8-bromoguanosine 3',5'-cyclic monophosphate induced relaxation. 3,4,5-Trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) or the removal of Ca2+ from the bathing medium attenuated the ACh-induced relaxation but did not significantly reduce vasorelaxation induced by ANG II or SNP. In the zero Ca2+ medium, aortic rings showed tachyphylaxis to ACh, while ANG II caused tachyphylaxis regardless of the presence or absence of external Ca2+. Furthermore, pretreatment of the ring with a high dose of ACh abolished the vasorelaxation response to ANG II, suggesting that ACh and ANG II may share a common Ca2+ pool. Calmidazolium, a calmodulin antagonist, abolished the vasorelaxation induced by ANG II and ACh but not that by SNP. Comparison of the vasodilatory effects of several ANG II analogues on fowl aortic rings showed an approximate potency order of [Asp1,Val5]-ANG II = [Asp1,Ile5]-ANG II > [Asn1,Ile5]-ANG II = [Sar1,Ile5]-ANG II > [Val5]-ANG III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498600 TI - Abdominal vagotomy decreases the satiating potency of CCK-8 in sham and real feeding. AB - To compare the effect of total abdominal vagotomy on the satiating potency of cholecystokinin COOH-terminal octapeptide (CCK-8) in sham feeding and real feeding, we administered CCK-8 intraperitoneally (2, 4, and 8 micrograms/kg) 1 min before a sham feeding or real feeding intake test. CCK-8 was at least as potent for inhibiting intake during sham feeding as it was during real feeding. Total abdominal vagotomy decreased the satiating potency of all three doses of CCK-8 equally in both feeding conditions. These results are consistent with the proposal that abdominal vagal afferent fibers are as necessary for the mediation of the satiating effect of CCK-8 in sham feeding as they are in real feeding. PMID- 8498601 TI - Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin. AB - Angiotensin (ANG) can produce a biphasic arterial pressure response, i.e., an increase followed by a decrease. Because ANG type 1 (AT1) receptors mediate the pressor response to ANG, we hypothesized that the opposing depressor action is mediated by the ANG type 2 (AT2) receptors. In thiobutabarbital (Inactin) anesthetized rats bolus injections of angiotensin III (ANG III; 100, 300, and 1,000 ng/kg iv) produced peak increases in MAP at 20 s of 13.4 +/- 1.4, 20.1 +/- 2, and 27.5 +/- 2.8 mmHg and maximum decreases in pressure at 120 s of -6.3 +/- 1.5, -6.8 +/- 2.2, and -11.4 +/- 4.9 mmHg. During blockade of the AT1 receptors with DuP 753 (losartan, 10 mg/kg) the increases in MAP were eliminated (P < 0.01), whereas the depressor responses (-24.7 +/- 8, -32.8 +/- 9.3, and -42.0 +/- 10.0 mmHg) were significantly (P < 0.05) larger. In separate groups of rats, combined blockade of both AT1 and AT2 receptors eliminated all changes in MAP in response to ANG III, whereas blockade of AT2 receptors alone enhanced the pressor response to ANG III. During AT1 receptor blockade angiotensin II also caused consistent decreases in pressure, which were inhibited during combined blockade of AT1 and AT2 receptors. Therefore, we have demonstrated that the AT2 receptors mediate a depressor response to ANG. PMID- 8498602 TI - Induction and prevention of low-T3 syndrome in exercising women. AB - To investigate the influence of exercise on thyroid metabolism, 46 healthy young regularly menstruating sedentary women were randomly assigned to a 3 x 2 experimental design of aerobic exercise and energy availability treatments. Energy availability was defined as dietary energy intake minus energy expenditure during exercise. After 4 days of treatments, low energy availability (8 vs. 30 kcal.kg body wt-1.day-1) had reduced 3,5,3'-triiodothyronine (T3) by 15% and free T3 (fT3) by 18% and had increased thyroxine (T4) by 7% and reverse T3 (rT3) by 24% (all P < 0.01), whereas free T4 (fT4) was unchanged (P = 0.08). Exercise quantity (0 vs. 1,300 kcal/day) and intensity (40 vs. 70% of aerobic capacity) did not affect any thyroid hormone (all P > 0.10). That is, low-T3 syndrome was induced by the energy cost of exercise and was prevented in exercising women by increasing dietary energy intake. Selective observation of low-T3 syndrome in amenorrheic and not in regularly menstruating athletes suggests that exercise may compromise the availability of energy for reproductive function in humans. If so, athletic amenorrhea might be prevented or reversed through dietary reform without reducing exercise quantity or intensity. PMID- 8498603 TI - Modulation of tissue-type plasminogen activator by retinoids in rat plasma and tissues. AB - In this study the effect of vitamin A status and retinoid treatment on the activity of tissue-type plasminogen activator (TPA) and its inhibitor, plasminogen activator inhibitor-type 1 (PAI-1), in plasma and in several tissues was investigated in BN/BiRij rats. Hypervitaminosis A and retinoic acid treatment increased plasma TPA activity by approximately 50%, but PAI-1 activity was not affected. The effect of retinyl palmitate treatment on plasma TPA activity was already significant after 5 days and continued for at least up to 8 wk. Isotretinoin treatment affected neither plasma TPA nor PAI-1 activity. In plasma of vitamin A-deficient rats, TPA activity was decreased by a factor of three, whereas PAI-1 activity was increased twofold. Modulation of plasma TPA activity by vitamin A status and retinoic acid treatment was associated with similar changes in tissue TPA activity. This suggests that the changes in plasma TPA activities might be the result of changes in tissue TPA synthesis. PMID- 8498604 TI - Role of the spinal cord in generating the 2- to 6-Hz rhythm in rat sympathetic outflow. AB - In baroreceptor-denervated animals, sympathetic nerve discharge (SND) displays a 2- to 6-Hz rhythm. Current theories suggest that this rhythm is generated by a neural oscillator in the medulla. In urethan-anesthetized rats, we have examined the effect on the 2- to 6-Hz rhythm of lumbar SND produced by 1) altering the firing pattern of a major output of this medullary network [the rostral ventrolateral medulla (RVLM)] and 2) disrupting the interactions between medulla and spinal cord (SC). Microinjection of muscimol [gamma-aminobutyric acid (GABA) agonist] unilaterally or a mixture of kynurenic acid (KYN; broad spectrum, excitatory amino acid antagonist) and bicuculline (GABAA antagonist) bilaterally into RVLM produced little effect on the 2- to 6-Hz rhythm. Intrathecal injection of KYN or transection of the cervical SC also had little effect once SND had been restored by intrathecal injection of kainic acid (excitatory amino acid agonist). Thus, whereas an excitatory input to the spinal cord is required for the generation of basal SND, patterning of this input is not critical for production of the 2- to 6-Hz SND rhythm that, in this species, may be essentially of spinal origin. PMID- 8498605 TI - Coronary blood flow in vivo in the coho salmon (Oncorhynchus kisutch). AB - The effects of adrenergic agonists on dorsal aortic blood pressure, cardiac output, and coronary blood flow were studied in unrestrained coho salmon, Oncorhynchus kisutch. Resting coronary blood flow was 0.43 ml.min-1.kg body mass 1, which represented 1.1% of cardiac output or approximately 0.5 ml.min-1.g-1 compact ventricular mass calculated on 40% of total ventricle mass. Coronary blood flow was phasic and continuous throughout the cardiac cycle; flow seems to be affected by the ventricular contraction, with a peak flow occurring during diastole and a nadir in early systole. Epinephrine injections into the dorsal aorta resulted in a rapid increase in coronary blood flow in association with a rapid increase in dorsal aortic blood pressure. Subsequently there was also a slower increase in coronary vascular resistance, which could be blocked by phentolamine, indicating an alpha-adrenergic vasoconstriction. Isoprenaline injection produced an increase in coronary blood flow and a large reduction in coronary vascular resistance. The coronary vasodilatation was blocked by propranolol, indicating that it may be partly due to a beta-adrenergic vasodilatation. Preliminary results showed a marked increase in coronary blood flow associated with exposure to environmental hypoxia. PMID- 8498606 TI - Suppression of sham feeding by intraintestinal nutrients is not correlated with plasma cholecystokinin elevation. AB - To test the possibility that blood-borne cholecystokinin (CCK) participates in suppression of sham feeding by intestinal nutrients in rats, we examined the ability of oleate, maltose, L-phenylalanine (L-Phe), and casein to suppress sham ingestion of 15% sucrose solution. Plasma CCK concentrations were measured in parallel experiments in which the same intestinal nutrients were infused in rats that were not feeding. Intraintestinal oleate suppressed sham feeding and elevated plasma CCK concentrations. Casein infusion produced plasma CCK concentrations similar to those produced by oleate but did not suppress sham feeding. Both maltose and L-Phe suppressed sham feeding but failed to significantly elevate plasma CCK. Previously we demonstrated that CCK receptor antagonists attenuate suppression of sham feeding by intestinal infusion of either oleate or maltose, suggesting that endogenous CCK participates in suppression of sham feeding by some intestinal nutrients. The results of the study reported here suggest that plasma CCK levels after nutrient infusion are not correlated with suppression of sham feeding. Therefore, the mechanism of CCK's participation in nutrient-induced suppression of sham feeding may not depend on stimulus-induced elevation of plasma CCK. PMID- 8498607 TI - ATP-MgCl2 restores gut absorptive capacity early after trauma-hemorrhagic shock. AB - The aim of this study was to determine whether ATP-MgCl2 as an adjunct to resuscitation has any beneficial effect on the depressed gut absorptive capacity (GAC) after hemorrhage and, if so, whether alterations in whole blood viscosity (WBV) are, in part, responsible for those effects. Rats were anesthetized, a laparotomy was performed (i.e., trauma induced), and blood vessels were cannulated. The animals then underwent fixed pressure (40 mmHg) hemorrhage, followed by resuscitation with lactated Ringer solution. One group received 50 mumol/kg ATP-MgCl2 and another received saline during resuscitation. At 2 and 4 h after the end of hemorrhage, a 1-h D-xylose absorption test was performed. Viscosity determinations were made at corresponding time points in another set of rats subjected to sham hemorrhage, acute hemodilution, or hemorrhage and resuscitation. Results show that xylose absorption is depressed after hemorrhage and resuscitation and that ATP-MgCl2 restored it to normal. D-Xylose absorption was inhibited by glucose, indicating a facilitated transport process. Furthermore, WBV was reduced by the administration of ATP-MgCl2. Thus ATP-MgCl2 improves GAC early after hemorrhage and resuscitation, possibly by reducing WBV, and may be a useful adjunct to resuscitation, allowing for early enteral nutrition. PMID- 8498608 TI - Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. AB - The protective effect of vitamin E supplementation on exercise-induced oxidative damage was tested in 21 male volunteers. Nine young (22-29 yr) and 12 older (55 74 yr) sedentary male subjects participated in a double-blind protocol and received either 800 IU dl-alpha-tocopherol or a placebo daily. After 48 days, vitamin E supplementation significantly increased alpha-tocopherol in plasma and skeletal muscle. Subjects then performed a bout of eccentric exercise at 75% of their maximum heart rate by running down an inclined treadmill for 45 min. All vitamin E-supplemented subjects excreted less (P < 0.05) urinary thiobarbituric acid adducts after the exercise bout than placebo subjects at 12 days postexercise (35 and 18% above baseline in young and old supplemented groups, respectively, vs. 60 and 80% in young and old placebo groups, respectively). After exercise, the initial difference in alpha-tocopherol concentration of muscle between young placebo and vitamin E-supplemented groups was diminished and muscle lipid conjugated dienes tended to increase (P = 0.09) in placebo subjects. Placebo subjects had a significant decrease in major fatty acids of muscle biopsy taken immediately after exercise. When normalized for the hemoconcentration effects of exercise, the plasma concentration of vitamins E and C and uric acid showed no significant change. The alterations in fatty acid composition, vitamin E, and lipid conjugated dienes in muscle and in urinary lipid peroxides in controls after eccentric exercise are consistent with the concept that vitamin E provides protection against exercise-induced oxidative injury. PMID- 8498609 TI - Endothelium-derived factors modulate contraction of bronchial smooth muscle. AB - Experiments were designed to determine how changes in the ratio of specific vascular endothelium-derived factors might affect reactivity of bronchial smooth muscle. The epithelium was mechanically removed from rings of third-order canine bronchi, and the rings were suspended in organ chambers for measurement of isometric force. Rings of pulmonary artery were cut; in some the endothelium was mechanically removed. The arterial rings were everted and pairs, with and without endothelium, were incubated with control solution, NG-monomethyl-L-arginine (L NMMA), indomethacin, or both L-NMMA and indomethacin for 90 min. They were then inserted into the lumen of the bronchial rings. Cumulative concentration-response curves to acetylcholine and 5-hydroxytryptamine were obtained. There was no significant difference in response between bronchi containing arteries with or without endothelium incubated with control solution. Contractions of bronchi containing arteries without endothelium, incubated in either L-NMMA or indomethacin, increased from control. However, in rings containing arteries with endothelium, incubation with either inhibitor decreased bronchial contractions. Incubation with both inhibitors eliminated the difference. These results suggest that the vascular endothelium produces factors that can both contract and relax bronchial smooth muscle. With inhibition of production of either nitric oxide with L-NMMA or prostanoids with indomethacin, release of other endothelium derived factors occurs that attenuates contractions of bronchial smooth muscle. Therefore, an imbalance in the ratio of production of endothelium-derived factors may contribute to bronchospastic disorders. PMID- 8498610 TI - Prior, duplicate, repetitive, fragmented, and redundant publication and editorial decisions. PMID- 8498611 TI - Preventing substance use: rethinking strategies. PMID- 8498612 TI - Paradigms and prevention. PMID- 8498613 TI - Distinguishing health expectancies and health-adjusted life expectancies from quality-adjusted life years. PMID- 8498614 TI - Alcohol, the heart, and health. PMID- 8498615 TI - Commentary: alcohol, the heart, and public policy. PMID- 8498616 TI - The conflict between public health goals and the temperance mentality. AB - OBJECTIVES: The prevailing view today is that alcohol consumption is unambiguously a social and public health problem. This paper presents evidence to balance this view. METHODS: Evidence of beneficial effects of alcohol against coronary artery disease is examined, together with cultural reasons for resistance in the United States to the implications of this evidence. RESULTS: Alcohol use reduces the risk of coronary artery disease--the major cause of heart disease, America's leading killer--even for those at risk for such disease. Moreover, recent research indicates that alcohol continues to reduce risk at the higher levels of drinking measured in general populations. However, with consumption of more than two drinks daily, these gains are increasingly offset by greater mortality from other causes. CONCLUSIONS: Educators, public health commentators, and medical investigators are uneasy about findings of healthful effects of drinking. A cultural preoccupation with alcoholism and the negative effects of drinking works against frank scientific discussions in the United States of the advantages for the cardiovascular system of alcohol consumption. This set has deep roots in American history but is inconsistent with public health goals. PMID- 8498617 TI - High-density lipoprotein cholesterol and alcohol consumption in US white and black adults: data from NHANES II. AB - OBJECTIVES: High-density lipoprotein (HDL) cholesterol is known to be positively related to moderate alcohol consumption from studies in selected populations. This study describes the association in a representative sample of the US adult population. METHODS: Stratification and multivariate regression analyses were used to examine HDL cholesterol levels and alcohol consumption. RESULTS: Fewer women than men reported consumption of alcohol at any frequency. Similar percentages of Whites and Blacks reported alcohol consumption. Age-adjusted mean HDL cholesterol levels were higher among alcohol drinkers than among nondrinkers in all sex-race strata. Mean HDL cholesterol levels of Whites and Blacks of both sexes increased consistently with increased frequency of consumption of beer, wine, and liquor. With age, education, body mass index, smoking, and physical activity controlled for, there were higher age-adjusted HDL cholesterol levels with increasing reported quantities of alcohol consumed. Daily or weekly use of alcohol led to an increase of 5.1 mg/dL in mean HDL cholesterol level, whereas consumption of 1 g of alcohol led to an increase of 0.87 mg/dL. CONCLUSION: Even if there is a causal association between alcohol consumption and higher HDL cholesterol levels, it is suggested that efforts to reduce coronary heart disease risks concentrate on the cessation of smoking and weight control. PMID- 8498618 TI - Alcohol-related mortality in California, 1980 to 1989. AB - OBJECTIVES: This study sought to examine the impact of alcohol use and misuse on mortality in California during the 1980s. METHODS: Alcohol-Related Disease Impact estimation software and California vital statistics data were used to calculate alcohol-related mortality, mortality rates, and years of potential life lost. Statistical tests were applied to detect significant differences in death rates by sex and race/ethnicity. Time trends in death rates for a subset of alcohol defined diagnoses were examined using regression analysis. RESULTS: An estimated 6.2% of all deaths for California residents during 1989 were related to alcohol, making it one of the top 10 leading causes of death. Injury diagnoses were major contributors to the total estimated number of alcohol-related deaths and years of potential life lost before age 65. Alcohol-related mortality rates were significantly higher for men and for Blacks. However, age-adjusted death rates for alcohol-defined diagnoses declined significantly from 1980 to 1989. CONCLUSIONS: A structured data-base approach to analyzing mortality data represents an important advance for alcohol research that has implications for policy and program planning. Future refinements and enhancements to the disease impact estimation methodology will add precision to determining how alcohol use and misuse affect public health in California. PMID- 8498619 TI - Alcohol and drug problems among diverse health and social service populations. AB - OBJECTIVES: This study responds to clinical and research interest in identifying alcohol- and drug-related problems in health and social service agency populations. These problems are associated with a variety of illnesses and social problems, and community agencies serve important screening functions. METHODS: Indicators of problematic alcohol and drug use are compared across representative samples of clients within a county's alcohol, mental health, and drug treatment systems; hospital emergency rooms; primary health clinics; criminal justice and welfare systems; and general population. RESULTS: Agencies followed a consistent rank ordering in the prevalence of substance abuse indicators. Highest prevalences were found in the populations of behavioral health agencies, including alcohol, drug, and mental health treatment facilities and criminal justice, followed by welfare agencies. General medical agencies served populations with the lowest prevalence and problem severity. CONCLUSION: Health and social service agencies provide significant opportunities for the screening and referral of individuals with problematic alcohol and drug use. Although behavioral agencies have higher potential for referral and intervention, general medical services may be more effective in conducting prevention and early case finding activities. PMID- 8498620 TI - Level of education and alcohol abuse and dependence in adulthood: a further inquiry. AB - OBJECTIVES: Prospectively gathered data were used to reexamine and to strengthen previously described observations about education and the risk of alcohol abuse and dependence. The hypothesis was that individuals who dropped out of high school and those who entered college but failed to get a college degree might be at increased risk for an alcohol disorder. METHODS: Study subjects were selected between 1980 and 1984 by taking probability samples of roughly 3000 adult household residents at each of the five Epidemiologic Catchment Area Program survey sites. To assess the occurrence of psychiatric conditions, staff administered the Diagnostic Interview Schedule soon after sampling and again at follow-up, roughly 1 year later. RESULTS: Individuals who had dropped out of high school were 6.34 times more likely to develop alcohol abuse or dependence than were individuals with a college degree. For those who had entered college but failed to achieve a degree, the estimated relative risk was 3.01. To extend these analyses, estimates for annual incidence were calculated, and an exploratory evaluation of interaction is presented. CONCLUSIONS: If these findings can be replicated, they should help identify subgroups at higher risk for the development of alcohol disorders. PMID- 8498621 TI - The prevalence of alcohol-related mortality in both sexes: variation between indicators, Stockholm, 1987. AB - OBJECTIVES: The purpose of this study was to analyze the prevalence rates of alcohol-related mortality--according to various indicators--in both sexes in Stockholm, Sweden. METHODS: A study of alcohol involvement at death was undertaken for all 668 deceased persons aged 15 through 54 years in 1987 in Stockholm. Death certificates, autopsy information, police records, and information about earlier conviction were analyzed. RESULTS: When different measures of estimation were compared, there were great differences in the prevalence rates of alcohol involvement. According to the death certificates, 9.2% of the males and 11.2% of the females had alcoholism, alcohol intoxication, pancreatitis or liver cirrhosis as underlying cause of death. When all accessible information was used, potential alcohol involvement was found in 57.5% of the male and in 32.2% of the female deaths. There was a marked association between earlier drunken driving and alcohol involvement. After reevaluation of the diagnoses with autopsy findings, the number of cases with cardiac enlargement and suspected cardiomyopathy increased from 10 to 62. CONCLUSION: The results point to the serious underdiagnosis of alcohol involvement in death certificates and the misclassification of important causes of death (i.e., liver cirrhosis and cardiac disease); they also call for increased efforts regarding prevention. PMID- 8498622 TI - Predictors of alcoholism in young Swedish men. AB - OBJECTIVES: The purpose of the study was to assess risk indicators for admission for alcoholism in young men. METHODS: Level of alcohol consumption and background variables were analyzed in a survey of 49,464 Swedish conscripts. Admissions to psychiatric care were registered during a 15-year follow-up. RESULTS: A strong association was found between level of alcohol consumption at conscription and future admission for alcoholism. The strongest risk indicator for admission for alcoholism, however, was "Contacts with police or child care authorities," with an odds ratio of 4.9. CONCLUSIONS: For conscripts reporting moderate alcohol consumption at conscription there was a clear association between an increasing burden of risk indicators and future alcoholism. Among men who already had a high level of alcohol consumption at conscription, additional risk indicators, with the exception of psychological factors, had relatively little impact on future admission for alcoholism. Poor emotional control and early symptoms of mental disorder, however, were instrumental not only in enhancing the risk for high consumption at conscription, but also in enhancing the risk for high consumers to become abusers or addicted. PMID- 8498623 TI - From beer to crack: developmental patterns of drug involvement. AB - OBJECTIVES: Prior research has identified developmental stages in drug use in adolescence, from substances that are legal for adults to illicit drugs. The position of crack in patterns of drug involvement remains to be established. METHODS: The analyses are based on a sample (n = 1108) representative of 12th graders attending New York State public and private schools. From reported ages of first use of five classes of drugs (alcoholic beverages, cigarettes, marijuana, cocaine but not crack, crack), alternate models of progression were tested for their goodness of fit through log-linear models. RESULTS: The sequence involves at the earliest stage the use of at least one licit drug, alcohol or cigarettes. Subsequent stages involve marijuana and cocaine; crack is the last drug in the sequence. The results confirm the more important role of alcohol among males and cigarettes among females in the progression into various drug classes. Age of first drug use at a lower stage is a strong predictor of further progression. CONCLUSIONS: The developmental pattern of drug involvement identified in the early 1970s still characterizes adolescent pathways of drug involvement in the late 1980s. PMID- 8498624 TI - Preventing adolescent drug use: long-term results of a junior high program. AB - OBJECTIVES: Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents, few have assessed the long term effects of such programs. Such information is essential for judging how long prevention benefits last. This paper reports results over a 6-year period for a multisite randomized trial that achieved reductions in drug use during the junior high school years. METHODS: The 11-lesson curriculum, which was tested in 30 schools in eight highly diverse West Coast communities, focused on helping 7th and 8th grade students develop the motivation and skills to resist drugs. Schools were randomly assigned to treatment and control conditions. About 4000 students were assessed in grade 7 and six times thereafter through grade 12. Program effects were adjusted for pretest covariates and school effects. RESULTS: Once the lessons stopped, the program's effects on drug use stopped. Effects on cognitive risk factors persisted for a longer time (many through grade 10), but were not sufficient to produce corresponding reductions in use. CONCLUSIONS: It is unlikely that early prevention gains can be maintained without additional prevention efforts during high school. Future research is needed to develop and test such efforts. PMID- 8498625 TI - Preschool children at high risk for measles: opportunities to vaccinate. AB - OBJECTIVES: In 1989 and 1990 the United States experienced a measles epidemic with more than 18,000 and 27,000 reported cases, respectively. Nearly half of all persons with measles were unvaccinated preschool children under 5 years of age. We sought to identify potential sites for vaccine delivery. METHODS: Preschool children with measles were surveyed in five inner cities with measles outbreaks in 1989 to 1990 to assess the children's use of health care services and federal assistance programs before contracting measles. RESULTS: Of 972 case children surveyed, 618 (64%) were eligible for measles vaccination at measles onset. Of those, 93% had previously visited a health care provider (private physician, public clinic, hospital emergency department, or hospital outpatient department) and 65% were enrolled in a federal assistance program (AFDC, WIC, or food stamps). Based on parent-reported reasons for health care visits, in Dallas and New York City, health care providers of 24% of 172 children may have missed at least one opportunity to administer measles vaccine. CONCLUSIONS: Many potential opportunities exist to raise the vaccination coverage of unvaccinated preschool children. These opportunities depend on (1) health care providers taking advantage of all opportunities to vaccinate, and (2) immunization services being linked to federal assistance programs. PMID- 8498626 TI - Congenital hypothyroidism screening and the cutoff for thyrotropin measurement: recommendations from The Netherlands. AB - OBJECTIVES: There is little agreement as to the optimal cutoff point for thyrotropin testing in primary thyroxine screening programs for congenital hypothyroidism. Most programs in the United States use a cutoff point of 10% of the lowest thyroxine values, whereas in the Netherlands a cutoff point of 20% is used. Therefore, the results of the Dutch program may provide valuable information about the optimal cutoff point. METHODS: The frequency distribution of screening thyroxine values was studied in all cases of permanent primary congenital hypothyroidism (n = 481) detected in 1,601,603 screened children born during the period from January 1, 1981, to December 31, 1989, in the Netherlands. RESULTS: Programs using a 10% cutoff point would have missed 1.5% of cases. Above the 10% cutoff point, the marginal costs increase quite rapidly because of the escalating numbers of thyrotropin measurements necessary to detect one case of permanent primary congenital hypothyroidism: 20,000 in the range of 11% to 15% and 40,000 in the range of 16% to 20%. CONCLUSIONS: Based on these findings, a cutoff point of at least 10% is recommended. PMID- 8498627 TI - A meta-analysis of adolescent smoking prevention programs. AB - OBJECTIVES: A large number of studies evaluating adolescent smoking prevention programs have been published. Systematic quantitative reviews of this literature are needed to learn what does and does not work. The present meta-analysis focuses on the efficacy of school-based programs. METHODS: Evaluations of 94 separate interventions were included in the meta-analysis. Studies were screened for methodological rigor and those with weaker methodology were segregated from those with more defensible methodology; major analyses focused on the latter. RESULTS: Behavioral effect sizes were found to be largest for interventions with a social reinforcement orientation, moderate for interventions with either a developmental or a social norms orientation, and small for interventions with the traditional rational orientation. Attitude effect sizes followed the same pattern, but knowledge effect sizes were similar across all four orientation categories. CONCLUSIONS: Because behavioral effect represents the fundamental objective of programs for prevention of adolescent tobacco use, the present results indicate that school-based programs should consider adopting interventions with a social reinforcement, social norms, or developmental orientation. PMID- 8498628 TI - Cardiovascular diseases in a Canadian Arctic population. AB - OBJECTIVES: The purpose of this study was to review cardiovascular mortality, morbidity, and risk factors in the multiethnic population of the Northwest Territories, Canada. METHODS: We analyzed death certificates and hospital records, and used a community health and examination survey. RESULTS: The age standardized mortality rate for ischemic heart disease (but not for other heart diseases or stroke) among the Northwest Territories population was lower than among the Canadian population. Among the indigenous Inuit/Eskimos and Indians, the age-standardized mortality rate for all circulatory diseases was lower than Canadians. Among Indian women, the rate approached the Canadian rate and exceeded that of Inuit and non-Natives. Compared with residents of Manitoba, Northwest Territories Inuit adults had a higher prevalence of smoking in all age-sex groups. Obesity was prevalent among older Inuit women and hypertension among young Inuit men. Except for women aged 25 to 44, the total cholesterol and triglyceride levels among Inuit were lower than or not different from Manitoba residents. Relatively high levels of high-density lipoprotein were found in older Inuits. CONCLUSIONS: The epidemiologic pattern of cardiovascular diseases in Arctic Canada differs from that among non-Native, southern Canadians. Rapid sociocultural changes may alter the situation, and health agencies must anticipate such transitions and intensify culturally appropriate control programs. PMID- 8498629 TI - Moderate drinking and coronary heart disease mortality: evidence from NHANES I and the NHANES I Follow-up. AB - Data from the National Health and Nutrition Examination Survey, conducted from 1971 through 1974, and the National Health and Nutrition Examination Survey Follow-up, conducted from 1982 through 1984, were used to test for a beneficial effect of moderate alcohol consumption on coronary heart disease mortality among White men and women. Evidence of such an effect was found for White men; accelerated time-to-failure models showed 3% to 4% longer life spans for moderate drinkers than for nondrinkers or light drinkers. PMID- 8498630 TI - Acculturation and alcohol consumption in Puerto Rican, Cuban-American, and Mexican-American women in the United States. AB - Data from the Hispanic Health and Nutrition Examination Survey were used to examine the influence of acculturation on alcohol consumption among Puerto Rican, Cuban-American, and Mexican-American women in the United States. Acculturation was found to be positively related to frequency of consumption and probability of being a drinker among all three groups. A positive relationship was also evident for total drinks consumed among Cuban-American women, and volume (drinks per occasion) and total drinks consumed among Mexican-American women. PMID- 8498631 TI - Two random repeat recall methods to assess alcohol use. AB - Two random repeat recall methods were compared with a summary measure to assess alcohol use. Subjects (n = 142) were randomly assigned to one of two groups; they were called either on 14 random days during three 30-day waves and asked about drinking yesterday, or on 2 random days during each wave and asked about drinking in the past week. Follow-up telephone interviews obtained summary measures for each wave. Random repeat methods generally obtained higher estimates. However, the high dropout rate makes questionable the feasibility of using this approach with general population samples. PMID- 8498632 TI - Telephone vs face-to-face interviewing in a community psychiatric survey. AB - This study compared telephone with face-to-face interviewing in a community psychiatric survey. Two groups of women were investigated, Holocaust survivors and Europe-born respondents who were in prestate Israel during World War II. Both were administered the Psychiatric Research Interview Demoralization Scale and a short item scale investigating World War II experiences. Results showed a high compliance rate to the telephone mode. The subjects' scores in the two modes were highly correlated. Telephone interviewing seems to be a reliable and efficient method in areas with a well-developed network of subscribers. PMID- 8498633 TI - Religious advance directives: the convergence of law, religion, medicine, and public health. AB - Because of the deep interpersonal significance of decisions made at the end of life, it is not surprising that religion has played an important role in patient and family decision making. Specific religious concerns about death and dying have led to religious advance directives. Advance directives offer a case study of models of interaction between religious communities and secular institutions. This paper examines why such directives have been created and how they may affect health care decisions. An analysis of their strengths and weaknesses concludes that specific religious instructions are unnecessary in written directives and may undermine both the religious and health care goals of patients. PMID- 8498634 TI - Helping nurse-midwives provide obstetrical care in rural North Carolina. PMID- 8498635 TI - New York City's Metropolitan Area Breast Cancer Awareness Partnership. PMID- 8498636 TI - Excise tax increases and cigarette sales. PMID- 8498637 TI - Pennsylvania's birth rates after Medicaid abortion restrictions. PMID- 8498638 TI - Women's sexual behaviors: only half the picture. PMID- 8498639 TI - Bone marrow transplantation using alternative donors. Mismatched related donors or closely matched unrelated donors. AB - PURPOSE: Bone marrow transplantation has been used with increasing frequency for the treatment of children with leukemia that is resistant to conventional therapy or in cases that have initial features indicating a poor prognosis. PATIENTS AND METHODS: For those children who are in need of a transplant but who do not have a matched sibling as bone marrow donor, transplantation can be performed with marrow from either a closely matched unrelated donor or from a partially matched family member. RESULTS: Comparable results have been reported for transplants using either one of these alternative types of donor marrow, but these results are not as good as those using HLA-matched siblings as donors. CONCLUSIONS: Delays in engraftment, increased infection rates, and complications related to graft-versus-host disease makes transplants using marrow from alternative donors more difficult and less successful. Improved methods to control graft-versus-host disease and greater ability to prevent infections, particularly opportunistic viral infections, will increase the success rate for marrow transplants using alternative donors. In addition, expansion of the National Marrow Donor Registry increases the likelihood of finding unrelated donors for children requiring such transplants. PMID- 8498640 TI - Choosing an alternative bone marrow donor among available family members. AB - PURPOSE: Bone marrow transplantation (BMT) can be curative for patients with hematological malignancies, marrow failure syndromes, and certain metabolic disorders. However, fewer than half of the patients who could benefit have a donor who is either an HLA-matched sibling or a phenotypically similar unrelated volunteer. PATIENTS AND METHODS: The opportunity for allogeneic bone marrow transplantation is significantly increased by the use of partially mismatched, haploidentical related donors. The likelihood of finding a donor within the family is dependent on the acceptable degree of mismatch on the unshared chromosome. The degree of mismatch is expected to be approximately 10% for a one antigen mismatch, 20-30% for a two-antigen mismatch, and > 95% for a three antigen mismatch. Improvements in transplant techniques designed to enhance engraftment and to prevent the development of severe acute and chronic graft versus-host disease have increased the feasibility of utilizing this readily available donor pool. Obviously, the ability to use a three-antigen mismatched related donor would make bone marrow transplantation available for almost every patient. RESULTS: Recent studies combining in vitro and in vivo immunomodulation of donor lymphocytes have resulted in consistent engraftment and control of acute graft-versus-host disease. CONCLUSIONS: These findings provide encouragement that there may need be no restriction on the availability of allogeneic marrow transplants as a therapeutic option for appropriate candidates. PMID- 8498641 TI - Autologous bone marrow transplantation in childhood acute lymphoid leukemia with use of purging. AB - INTRODUCTION: Chemotherapy alone is rarely curative for children with recurrent acute lymphoid leukemia (ALL). Although allogeneic bone marrow transplantation has been reported to provide disease-free survival rates of from 40 to 70%, its application is severely limited by the lack of sibling donors. The use of autologous bone marrow transplantation (ABMT) allows the application of therapy of comparable intensity to a larger number of patients. A potential problem associated with transplanting autologous marrow, the reinfusion of residual leukemic cells in the harvested marrow, can be addressed through purging. The most widely used purging techniques involve either immunologic or pharmacologic techniques. PATIENTS AND METHODS: Since 1980, the Dana-Farber Cancer Institute has had an active autologous bone marrow transplantation program for children with recurrent ALL. Sixty-six children underwent autologous marrow transplants with a conditioning regimen consisting of teniposide, cytarabine, cyclophosphamide, and total body irradiation. This was followed by infusion of autologous marrow purged with two monoclonal antibodies directed against CD9 and CD10 and complement. RESULTS: Twelve patients died of acute complications, 26 experienced relapse of ALL, one patient had acute myeloid leukemia 6 years after marrow transplant, and 27 remain in continuous complete remission. The event-free survival rate was 47% for patients with a first remission of at least 2 years, as compared with a rate of 10% for those with a shorter first remission. Since 1989, we have used a new conditioning regimen consisting of fractionated total body irradiation followed by high-dose etoposide and cyclophosphamide for patients with a short first remission. For the first 11 patients, the event-free survival rate is 61%. LITERATURE REVIEW: We reviewed reports of 552 patients with ALL who underwent ABMT at 17 centers. To our knowledge, only four series, including our own, were limited to pediatric patients. Some form of purging was used in 483 (87%) patients. Although conditioning regimens varied greatly, more than 80% of patients received at least total body irradiation and cyclophosphamide. Failure of engraftment was reported in only three patients. The rates of disease-free survival in these series clustered between 25-35%. The most common cause of treatment failure after ABMT was relapse, which occurred in 40-85% of patients. Early deaths from toxicity occurred in 5-21% of patients. Two studies attempted to compare the results of allogeneic and autologous bone marrow transplantation by using the same conditioning regimen for all. Neither series reported significant differences in overall survival. PMID- 8498642 TI - The graft-vs.-leukemia effect. Implications for post-marrow transplant antileukemia treatment. AB - PURPOSE: Over the past 30 years, evidence supporting the existence of an antileukemic effect of allogeneic bone marrow has rapidly expanded. Early animal studies demonstrated this "graft-vs.-leukemia" (GVL) effect in association with graft-vs.-host disease (GVHD). PATIENTS, METHODS, AND RESULTS: Clinical evidence for the GVL effect derived from experience in allogeneic bone marrow transplantation (BMT) includes the following: the association of GVHD, both acute and chronic, with a decreased rate of leukemic relapse, the occurrence of a higher relapse rate following identical twin transplants compared to allogeneic major histocompatibility complex-matched sibling transplants, the decrease of GVHD and increase of leukemic relapses with T-cell depletion of donor bone marrow, and that allogeneic marrow transplants without GVHD have a lower leukemic relapse rate compared to identical twin transplants and T-cell depleted transplants. In addition, some reports indicate that modifying the immunosuppressive regimens (consisting of cyclosporine A or methotrexate) that are aimed at prevention of GVHD can affect leukemic relapse rates. Although the mechanism of this GVL effect is poorly understood, there are several favored hypotheses. Cytotoxic T cells, which may mediate GVH effects, could also mediate a GVL effect. There may also be T cells with specificity for destroying leukemic blasts alone. The natural killer/lymphokine-activated killer cytotoxic cell may play a role in the GVL effect. These nonspecific cytotoxic cells can be activated with cytokines induced in the transplant setting. Finally, the GVL effect could be secondary to the in vivo induction of various cytokines that either have direct antileukemic effects or that induce leukemic differentiation. Advances in our basic understanding of the immune system and its activation, and the availability of purified immunoregulatory cytokines, have revealed new ways to induce GVL-like effects. Promising results with therapy based on use of interleukin-2 in solid tumors have been seen. It is hoped that these advances will enable the "antileukemic" components of the GVL effect to be prospectively controlled (as part of the technique of marrow transplant) and intentionally used as leukemic therapy in patients undergoing bone marrow transplantation. PMID- 8498643 TI - Neuropsychologic consequences of long-term human immunodeficiency virus infection. The hemophilia growth and development study. PMID- 8498644 TI - Hemophilia growth and development study. Design, methods, and entry data. AB - PURPOSE: The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. PATIENTS AND METHODS: Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. RESULTS: Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. CONCLUSIONS: Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison. PMID- 8498645 TI - The reversibly sickled cell. AB - PURPOSE: We have developed and applied simple techniques for the detection of irreversibly and reversibly sickled cells (ISCs and RSCs) in blood samples. Both ISCs and RSCs are found in the venous and arterial circulation, and sickling and unsickling occurs continuously in the tissues and arterial blood, respectively. PATIENTS AND METHODS: Using these techniques, we have studied the number of RSCs and ISCs in 100 children with sickle cell disease (SS) and 20 with sickle cell C disease (SC). RESULTS: Both RSC and ISC numbers were significantly higher in blood samples of children with SS than those with SC disease. The number of RSCs and ISCs bears a direct relationship to the severity of the hemolytic process but has a negative relationship to the frequency of vaso-occlusive crises. CONCLUSIONS: The manifestations of sickle cell disease appear not to be the result of large numbers of circulating sickled cells randomly lodging in vessels but more likely are the result of local vascular stasis with subsequent sickling and vaso-occlusion. PMID- 8498646 TI - Pediatric histiocytosis. Characterization, prognosis, and oral involvement. AB - PURPOSE: Forty-five children with histiocytosis were reviewed to characterize such a group and to establish the prevalence of oral involvement. In addition, patients with and without oral disease were compared for severity of disease, response to treatment, and incidence of recurrent disease. PATIENTS AND METHODS: There were more boys (62.2%) than girls (37.8%) among the patients studied. About half (53.3%) were < 2 years of age. Approximately half of all patients had two or fewer affected organ systems at diagnosis. The average length of treatment was 46 weeks. RESULTS: A total 75.6% of patients were alive without disease at the completion of data collection, 15.6% died from the disease, 4.4% were alive with active disease, and 4.4% were alive with unknown status. Of the patients, 55.6% had long-term sequelae, and oral sequelae were present in 22.2% of the sample. In all, 28.8% of the patients exhibited oral symptoms at diagnosis, while 44.4% had oral involvement at some point during the course of the disease. Patients with oral symptoms were treated significantly longer and had more systemic therapy when compared with those without oral disease. PMID- 8498647 TI - Magnetic resonance imaging of the brain and neuropsychological evaluation in children treated for acute lymphoblastic leukemia at a young age. AB - PURPOSE: To evaluate the adverse late effects of ALL treatment on cognitive functions and brain morphology; to integrate the results of a neuropsychological and neuroradiological study. PATIENTS AND METHODS: Cranial magnetic resonance imaging (MRI) and neuropsychological assessments (NA) were performed in 35 children treated for acute lymphoblastic leukemia (ALL) with cranial irradiation (CI) and intrathecal and intravenous methotrexate. Patients were under the age of 7 years (MD: 3.5 years) at diagnosis; median follow-up at MRI and NA was 8 years since diagnosis. RESULTS: MRI's were classified as definitely abnormal in 51% and as probably abnormal in another 17% of the patients. White matter damage was most frequently seen. MRI abnormalities were not related to CI dose or age at diagnosis. Patients showed significantly lower scores, compared to the norm group on measures of intelligence, verbal auditory memory, visual motor integration, and fine motor functioning. Lower scores significantly correlated with higher CI dose (25-32 Gy compared to 18-20 Gy) and younger age at diagnosis (< 4.0 years compared to > or = 4.0 years). Forty percent of the patients had to be referred to schools for learning disabled. CONCLUSIONS: ALL treatment, including CI and MTX, at a young age is associated with persistent cognitive impairment and MRI abnormalities. However, no correlation was found between MRI results and neuropsychological or academic performance. PMID- 8498648 TI - Serum interleukin-6 and fever at diagnosis in children with acute leukemia. AB - PATIENTS AND METHODS: We examined serum interleukin (IL)-6 and tumor necrosis factor (TNF) alpha levels at initial diagnosis in acute leukemic children in order to clarify the roles of these cytokines on the febrile and hematological responses in the disease. RESULTS: IL-6 levels were significantly higher in 34 leukemic children than in 18 healthy controls and 15 patients with various malignant diseases in long remission (p < 0.0001). Three patients with apparent bacterial infections showed especially high IL-6 levels of > 100 pg/ml. In all the leukemic children, the high IL-6 levels at initial diagnosis had decreased to a low range at the time of complete remission, regardless of the use of antibiotics. In 10 of 14 leukemic children, TNF levels were high at diagnosis and then decreased to undetectable levels at remission. The relationship between IL 6/TNF levels and clinical/laboratory findings in leukemic children at diagnosis was also examined. Serum IL-6 significantly correlated with elevated body temperature (BT) (p < 0.001) and C-reactive protein (CRP) levels (p < 0.001), but not with other parameters such as leukocyte and platelet counts, hemoglobin levels, lactate dehydrogenase, and serum immunoglobulin. On the other hand, serum TNF did not show any statistical linkage with these parameters. CONCLUSION: These data provide evidence for the role of IL-6 in the pathogenesis of tumor-related fever and other acute phase responses in acute leukemia. PMID- 8498649 TI - Central nervous system disease associated with Langerhans' cell histiocytosis. AB - PURPOSE: To study the pathogenesis of central nervous system (CNS) lesions in Langerhans' cell histiocytosis (LCH), discuss their differential diagnosis and suggest guidelines for their management. PATIENTS AND METHODS: Central nervous system (CNS) disease with Langerhans' cell histiocytosis (LCH) is a poorly understood disorder. Most commonly, the hypothalamic-pituitary region is involved, leading to diabetes insipidus (DI) or other endocrinopathies. We report four patients in whom lesions in the pons, cerebellum, basal ganglia, cerebral white matter, or optic nerve and tract were demonstrated by magnetic resonance imaging (MRI). RESULTS: Three developed a progressive neurological disorder with cerebellar and pontine symptoms leading to severe disability--in one patient to blindness and death--in spite of various treatment approaches. In the fourth patient, who had MRI examinations to evaluate long-standing DI, CNS lesions were detected in the absence of neurological symptoms. There was no correlation between activity of LCH, severity and course of the CNS disease, or morphology of the lesions on MRI. Brain biopsy was performed in the three symptomatic patients and revealed cerebellar atrophy in one. Normal brain tissue was obtained from two patients. In none of the patients could autoantibodies to nervous system tissue be detected in serum or cerebrospinal fluid. CONCLUSION: Based on clinical, pathological, and MRI findings in our four patients and on information in the literature, we conclude that the CNS disease associated with LCH, although insufficiently understood, is likely to be a manifestation of histiocytosis in the brain, and we propose guidelines for the management of patients with this disorder. PMID- 8498650 TI - Acute myeloid leukemia after single-agent treatment with etoposide for Langerhans' cell histiocytosis of bone. AB - The first case of secondary leukemia (FAB M3 microgranular variant) after single agent chemotherapy with etoposide is described. The peculiar morphology and the absence of previously described cytogenetic abnormalities make this case of interest and emphasize the need for further study of epipodophyllotoxin-related leukemia. PMID- 8498651 TI - Choriocarcinoma in children. PMID- 8498652 TI - Muscle pain after outpatient laparoscopy--influence of propofol versus thiopental and enflurane. AB - The incidence and pattern of postoperative muscle pains was studied in 155 healthy women undergoing outpatient laparoscopic surgery who were assigned randomly to one of five treatment groups. Group 1 (control) received thiopental and succinylcholine, 1 mg/kg, followed by enflurane and nitrous oxide. Group 2 received d-tubocurarine, 3 mg, followed by succinylcholine, 1.5 mg/kg, but was otherwise similar to Group 1. Groups 3 and 4 were similar to Group 1, but received propofol instead of thiopental, and Group 4 also received a variable rate propofol infusion instead of enflurane. Finally, Group 5 was similar to Group 3, but received atracurium instead of succinylcholine. Muscle fasciculations were often observed in Groups 1, 3, and 4, but were attenuated in Group 2 and absent in Group 5. Overall, postoperative shoulder pain occurred in 81%, 72%, and 29% of patients on the first, second, and third postoperative days, respectively. The incidence of this symptom did not differ among the five groups. Neck pain occurred less frequently than shoulder pain in each group, and also occurred less often in Group 5 than in Group 1. Muscle stiffness occurred less often than muscle pain, and also occurred less frequently in Group 5 than in Group 1. In conclusion, succinylcholine contributes to neck pain and muscle stiffness after laparoscopic procedures. Compared to thiopental and enflurane, the use of propofol for induction and/or maintenance of anesthesia failed to alter the incidence of postlaparoscopic muscle pain or stiffness. PMID- 8498653 TI - The effect of perfusion flow on oxidative metabolism during cardiopulmonary bypass. AB - The influence of perfusion flow rate on whole-body oxygen consumption (VO2), central venous hemoglobin oxygen saturation (SVO2), and central venous arterial oxygen tension (PVO2) during hypothermic hemodilutional nonpulsatile cardiopulmonary bypass was investigated in 20 patients undergoing coronary artery bypass grafting. In 10 patients, the perfusion flow was 2.4 L.min-1 x m-2 (Group I), whereas a flow of 1.2 L.min-1 x m-2 was used in the other 10 patients (Group II). When the body temperature was 29.7 +/- 1.2 degrees C (Group I) and 29.6 +/- 0.8 degrees C (Group II), mixed venous and arterial blood were sampled simultaneously, and whole-body oxygen consumption was calculated. Data collected during hypothermia were compared with the corresponding values achieved after rewarming to 37 degrees C. In both groups, the whole-body oxygen consumption during hypothermia was lower by about 45% than the VO2 after rewarming. However, SVO2 during the low perfusion flow was not significantly different from SVO2 after rewarming, whereas the temperature-corrected PVO2 was significantly lower. In contrast, the high-perfusion flow provided luxury perfusion as evident by the high SVO2, and maintained the temperature-corrected PVO2 within the normothermic range. Thus, maintenance of the normothermic perfusion flow rate during moderate hypothermic hemodilutional cardiopulmonary bypass may provide a safety margin that may compensate for unexpected increase of oxygen consumption or decrease of oxygen delivery. PMID- 8498654 TI - The effect of the pericardium on right and left ventricular diastolic functions during isoflurane anesthesia. AB - We examined the effects of the pericardium on diastolic function of the right and left ventricles during isoflurane anesthesia. The diastolic properties of the ventricles were assessed by indices of isovolumetric relaxation such as -dP/dt, dP/dt25, and time constant for relaxation, and by end-diastolic pressure. In seven mongrel dogs, anesthesia was initially induced by the administration of pentobarbital and maintained with alpha-chloralose. Two 7F microtipped pressure transducers were inserted into the right and left ventricles, and a flow-directed pulmonary artery catheter was placed in the pulmonary artery. After a left thoracotomy, opening and closing the pericardium was performed at 0% isoflurane, 1.3% isoflurane, and 2.6% isoflurane. Isoflurane 1.3% and 2.6% produced a decrease in cardiac output in association with a decrease in -dP/dt and an increase in time constant for relaxation of both ventricles, suggesting that isoflurane may depress isovolumetric relaxation of both ventricles. Isoflurane also increased end-diastolic pressure of the left ventricle. With 0% isoflurane, pericardial opening did not significantly change the diastolic properties of either ventricle and other hemodynamics. Pericardial opening at 1.3% and 2.6% isoflurane increased cardiac output without any significant changes in -dP/dt and time constant of either ventricle, but with significant decreases in end diastolic pressures of both ventricles. We conclude that the pericardium may have a constraining effect on the diastolic properties, especially end-diastolic pressure, but not on isovolumetric relaxation of both ventricles during isoflurane anesthesia. PMID- 8498655 TI - Early administration of amrinone does not impair regional metabolism of O2 or lactate and, by improving myocardial performance, preserves myocardial blood flow in the ischemic canine heart. AB - The inotropic and vasodilating effects of amrinone can upset the balance of O2 supply and demand by changing those components in opposite directions simultaneously. We used a canine model of acute coronary artery occlusion to test our hypothesis that early administration of amrinone (before failure of the heart) would have beneficial effects on hemodynamic status and regional metabolism during ischemia, even before heart failure. Twenty dogs anesthetized with thiamylal were subjected to 50%, 75%, and 100% occlusion of the left anterior descending coronary artery. Half of the dogs were given a bolus injection of amrinone (0.75 mg/kg) 1-2 min before each occlusion, immediately followed by continuous infusion (10 micrograms.kg-1 x min-1) during occlusion; the other half did not receive amrinone (control). Hemodynamic and metabolic variables were measured in the ischemic area (the left anterior descending coronary artery) and in a nonischemic area (the circumflex vein). Amrinone not only decreased heart rate, left ventricular systolic and end-diastolic pressures, and mean pulmonary arterial pressure during constrictions but also maintained contractility, stroke volume index, and stroke volume index/left ventricular end diastolic pressure before and during constrictions. Regional myocardial blood flow in ischemic areas decreased with amrinone during constrictions but was still higher than in untreated animals. Regional ischemic and nonischemic metabolic variables (metabolism of intracoronary potassium, CO2, O2, glucose, and lactate) were similar for both groups and changed to the same extent. Amrinone appears to improve left ventricular performance and increase blood flow to ischemic myocardium while not worsening regional metabolic effects during various grades of ischemia in the dog. PMID- 8498656 TI - Heparin prevents the vasodilating actions of protamine on human small mesenteric arteries. AB - Despite the wide clinical use of protamine, the precise mechanisms of its hypotensive effects during reversal of heparin anticoagulation have not been elucidated fully. We, therefore, investigated the effects of protamine on isolated human small mesenteric arteries, both in the absence and presence of heparin, employing the isometric tension recording method. Protamine exerted vasodilating actions in the absence of heparin: 1) protamine (> or = 50 or 150 micrograms/mL) inhibited (P < 0.05) both norepinephrine (1 microM)- and high K+ (40 mM)-induced contractions in the presence of extracellular Ca2+ both in endothelium-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 microM)-induced, but not caffeine (10 mM)-induced, contractions in the absence of extracellular Ca2+. Such vasodilating actions were blocked almost completely in the presence of heparin. We conclude that only protamine, but not a heparin-protamine complex, has a vasodilating action on the human arteries. PMID- 8498657 TI - Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs. AB - The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498658 TI - The effect of nicardipine on carotid blood flow velocity, local cerebral blood flow, and carbon dioxide reactivity during cerebral aneurysm surgery. AB - We studied the effects of nicardipine (initial infusion rate 0.5 micrograms.kg-1 x min-1) on blood flow velocity in the internal carotid artery, local cerebral blood flow (LCBF), and carbon dioxide reactivity in 20 patients undergoing craniotomy for cerebral aneurysm clipping under isoflurane anesthesia. The blood flow velocity in the internal carotid artery was measured at T0 and T3 by a 20 MHz pulsed ultrasound Doppler flowmeter. LCBF was measured by the thermal gradient blood flow meter. Group A consisted of 10 patients with a good neurologic status (Hunt and Kosnik Grade I); Group B consisted of 10 patients with a poor status (Grades II-IV). Nicardipine was infused until the mean arterial blood pressure decreased to about 75% of the initial value and was maintained at this level until the completion of aneurysm clipping. The measurements of hemodynamics and LCBF were performed after the exposure of the internal carotid artery (T0), and 10 and 30 min after the start of nicardipine (T1 and T2, respectively), before aneurysm clipping (T3), and 30 min after its discontinuation (T4). Carbon dioxide reactivity [% ALCBF/APaCO2 (%/mm Hg)] was evaluated at T0, T3, and T4. Mean arterial blood pressure decreased after nicardipine infusion in both groups. LCBF did not change during nicardipine infusion in either group. Blood flow velocity increased significantly in Group A after nicardipine infusion from 45.1 +/- 6.9 to 51.5 +/- 6.4 cm/s (P < 0.05), but in Group B flow velocity did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498659 TI - Ventilatory response to carbon dioxide in term infants after halothane and nitrous oxide anesthesia. AB - The purpose of this study was to determine whether the ventilatory response to CO2 is depressed in term infants after halothane and N2O anesthesia. Ventilatory response to CO2 was determined by using a maskless CO2 response test in which a ventilation ratio is calculated from measurements of transcutaneous PCO2 (PtcCO2). Ventilation ratio represents the fractional increase in ventilation that occurs in response to inspired CO2. Eight infants were studied who were at least 36 wk gestational age and 12 +/- 4 wk postnatal age, did not have apnea in the perioperative period (values are means +/- SD). Ventilation ratio measured with a 4%-inspired-CO2 stimulus increased significantly after anesthesia (3.5 +/- 0.8 vs 3.0 +/- 0.5, P = 0.02). Baseline PtcCO2 was significantly lower after anesthesia than before anesthesia (37 +/- 4 vs 42 +/- 3, P < 0.01) which may reflect the development of a relative metabolic acidosis. (The occurrence of postoperative metabolic acidosis was in fact documented in another group of eight infants.) Ventilatory response to CO2 was not depressed after halothane and nitrous oxide anesthesia in these term and near-term infants. PMID- 8498660 TI - The pharmacokinetics of droperidol in anesthetized children. AB - Despite the wide use of droperidol to reduce nausea and vomiting in children, its pharmacokinetics have not been described in pediatric patients. Twelve ASA Class I-II children, undergoing tonsillectomy and adenoidectomy, received standardized anesthesia; none of the children received premedication. After induction of general anesthesia, droperidol (0.05 mg/kg) was injected intravenously as a bolus. Droperidol plasma concentrations were determined by radioimmunoassay. Pharmacokinetic data were analyzed by model-independent methods. The pharmacokinetic parameters (mean +/- SD) for the studied population were elimination half-life: 101.5 +/- 26.4 min, mean residence time: 127.2 +/- 28.6 min, volume of distribution at steady state: 0.58 +/- 0.29 L/kg and clearance: 4.66 +/- 2.28 mL.kg-1 x min-1. The clearance and volume of distribution at steady state values are lower than those reported for the adult population, and they apparently decreased in a parallel fashion. The smaller volume of distribution at steady state is consistent with the lipophilic distribution of droperidol and the reduced content of adipose tissue in children. The elimination half-time and mean residence time values are similar to those reported previously for adults. The relatively short half-life of droperidol for our pediatric population does not explain its extended antiemetic action. It does, however, reaffirm that the pharmacokinetic duration of a drug's action is only one of the determinants of its clinical duration. PMID- 8498661 TI - A randomized double-blind comparison of epidural sufentanil versus intravenous sufentanil or epidural fentanyl analgesia after major abdominal surgery. AB - This randomized double-blind study compared epidural sufentanil (SEPI) with intravenous sufentanil (SIV) or epidural fentanyl (FEPI) analgesia in 45 patients after major abdominal operations. On first complaint of severe postoperative pain, SIV patients were given a 15-micrograms bolus and then a 5 micrograms/h infusion of sufentanil intravenously. SEPI patients were given the same bolus and infusion, but epidurally. FEPI patients had a 60-micrograms bolus and 20 micrograms/h infusion of fentanyl epidurally. All patients also received a bolus injection and then an infusion of coded saline via the alternate route. Analgesic requirements were tailored continuously to individual needs by patient-controlled supplementary boluses of 3.1 micrograms of sufentanil or 12.5 micrograms of fentanyl, or by 50% reduction in opiate infusion rate at predetermined intervals. Pain scores, circulatory variables, and respiratory rate did not differ between groups. Mean opiate dose requirements (+/- SD) to maintain analgesia for 24 h were 202 +/- 43 micrograms (SIV), 149 +/- 45 micrograms (SEPI), and 627 +/- 226 micrograms (FEPI). The relative analgesic potencies (AP) calculated from the equianalgesic dose requirement ratios were 1.4 for AP-sufentanil IV/EPI and 4.2 for AP-epidural F/S. SIV patients required more supplementary boluses than SEPI patients, were more sedated during the entire treatment, and had higher PaCO2 and higher serum sufentanil concentrations within the first 3 h of treatment. In addition, severe respiratory depression occurred in four SIV patients soon after the start of treatment, despite serum sufentanil concentrations of less than 0.3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498662 TI - Equivalence of postoperative analgesia with patient-controlled intravenous or epidural alfentanil. AB - The analgesia and the frequency and severity of oxyhemoglobin desaturation related to alfentanil administration were compared in 32 patients randomly selected to receive patient-controlled analgesia (PCA) by either the epidural (EPI) or intravenous (i.v.) route for a mean period of 16 h after major abdominal surgery. Bolus increments of 250 micrograms of alfentanil with a lockout interval of 5 min for i.v. and of 10 min for EPI route were administered by a programmable pump. Oxygen saturation (SpO2) was monitored for 16 h, using a pulse oximeter; data were collected continuously and stored every 30 s via an interface connected to a computer. For the purpose of analysis, SpO2 was divided into six categories: 95%-100%, 90%-94%, 85%-89%, 80%-84%, 75%-79%, and 70%-74%. Both routes provided similar degrees of analgesia at rest and on coughing. Maximum pain relief was obtained earlier in the i.v. group (P < 0.01). The total consumption of alfentanil was 13,141 +/- 3471 micrograms (mean +/- SD) in the i.v. group and 8000 +/- 4213 micrograms in the EPI group (P < 0.001). The effects on SpO2 were not statistically different between the two groups. Cumulative time spent in each saturation category was similar for the EPI and i.v. groups. Severe desaturation episodes, defined as SpO2 < or = 85% for at least 60 s, occurred in 69% of patients in the EPI group and 56% in the i.v. group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498663 TI - Potassium channel openers attenuate atrioventricular block by bupivacaine in isolated hearts. AB - Our purpose was to test if pinacidil and bimakalim (EMD 52692 or SR 44866), which are ATP-sensitive K+ (K+ATP) channel openers, can attenuate bupivacaine-induced atrioventricular (AV) block. Bupivacaine-induced AV block was studied in 24 isolated guinea pig hearts with or without either pinacidil or bimakalim. Hearts were perfused at 55 mm Hg with a modified Krebs' perfusate. Variables monitored were: heart rate, AV conduction time, left ventricular pressure, coronary flow, and myocardial oxygen extraction. Bupivacaine was infused at a constant concentration of 4 microM to induce first degree AV block and 15-25 microM to induce second degree heart block. During a stable AV block (e.g., first degree, 2:1, 3:2, or 4:3), K+ channel openers, pinacidil (up to 30 microM) or bimakalim (up to 2 microM) were added to perfusate containing bupivacaine. The effects of K+ channel openers were also examined in the presence of the selective K+ATP channel blocker, glibenclamide (2.2 microM). On the average, 4 microM bupivacaine prolonged AV conduction by 53%, and decreased heart rate by 13%, left ventricular pressure by 26%, coronary flow by 6%, and percent oxygen extraction by 7%. In the presence of bupivacaine, pinacidil and bimakalim additionally decreased left ventricular pressure and oxygen extraction, markedly increased coronary flow, and attenuated the prolongation of AV conduction by 20% with no further change in heart rate. The beneficial effect of bimakalim on AV block was reversed by glibenclamide. Second degree AV block produced by higher doses of bupivacaine was converted to first degree AV block by either pinacidil or bimakalim in 6 of 8 and 7 of 8 hearts, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498664 TI - Cardiac electrophysiologic effects of articaine compared with bupivacaine and lidocaine. AB - Articaine is a local anesthetic structurally different from lidocaine and bupivacaine in that it contains a thiophene ring. We compared its cardiodepressant effects with those of lidocaine and bupivacaine in a randomized, blinded study using the isolated rabbit heart preparation. The hearts were removed quickly from thiamylal anesthetized/killed animals. The right septal wall was placed in a warm, aerated, Tyrode's solution-perfused chamber. The effects of the three local anesthetics on action potentials from the Purkinje fiber (PF) and ventricular muscle (VM) tissues were determined. Bupivacaine (17.4 microM) and articaine (141 microM) depressed action potential overshoot, amplitude, and maximal rate of depolarization (Vmax) by similar amounts. Bupivacaine's effects persisted significantly longer than articaine and lidocaine (P < 0.05). Rate dependent decreases in steady-state (SS) Vmax were obtained with all three drugs. At their highest concentrations, bupivacaine (17 microM) and lidocaine (85 microM) produced decreases in SS Vmax from the first Vmax response. However, articaine (141 microM) increased SS Vmax at 1 and 2 Hz and only decreased SS Vmax at 3 Hz. During superfusion of a "bolus concentration" of the local anesthetics, bupivacaine blocked PF-VM conduction significantly longer than either articaine or lidocaine (P < 0.001). Articaine, at ten times its observed clinical blood concentration was significantly less cardiodepressant in these in vitro experiments than bupivacaine at five times its observed clinical blood concentration. PMID- 8498665 TI - A comparison of epidural 1% ropivacaine and 0.75% bupivacaine for lower abdominal gynecologic surgery. AB - A randomized double-blind study was performed to compare ropivacaine and bupivacaine in epidural anesthesia for intraperitoneal surgery. Forty-four patients undergoing epidural anesthesia for intraperitoneal lower abdominal gynecologic surgery received 20 mL of either 1% ropivacaine or 0.75% bupivacaine via an epidural catheter. There was no difference between the two drugs in the onset, extent, and duration of sensory and motor block. Satisfactory conditions for surgery were produced in the same number of patients in each group. The cardiovascular changes and the overall incidence of adverse reactions were similar for both drugs. It is concluded that ropivacaine is an effective and safe alternative to bupivacaine when used in epidural anesthesia for lower abdominal, intraperitoneal surgery. PMID- 8498666 TI - Spinal cord blood flow after intrathecal injection of a N-methyl-D-aspartate receptor antagonist or an adenosine receptor agonist in rats. AB - Evaluation of spinal cord blood flow (SCBF) is important as a preclinical screening for potential neurotoxicologic side effects before introducing new therapeutic drugs for intrathecal (IT) administration. This study was undertaken to determine whether two drugs with possible antinociceptive effects, the N methyl-D-aspartate receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1 phosphonic acid (CPP) and the adenosine agonist R-phenylisopropyladenosine (R PIA), would affect SCBF after IT administration in the rat. SCBF was measured 30 min after IT injection of either saline, 4 nmol of CPP or 10 nmol or R-PIA in anesthetized rats by quantitative autoradiography with [14C]iodantipyrine as a tracer. No differences in SCBF were found between groups treated with saline or CPP. In the group where R-PIA was administered IT, grey matter blood flow was 10% greater than in the group that received saline, whereas no differences were found in white matter blood flow or in the grey/white matter ratio between the groups. We concluded that neither CPP nor R-PIA, when administered IT to anesthetized rats in provocative doses within the upper pharmacologic dose range, reduces SCBF in rats 30 min after IT injection. This indicates that neither neurotoxicologic nor antinociceptive effects are likely to occur due to decrease in SCBF. Our results do not indicate that these drugs should be avoided for the treatment of pain. PMID- 8498667 TI - Pharmacodynamics of atracurium in clinical practice: effect of plasma potassium, patient demographics, and concurrent medication. AB - To determine which factors influenced the pharmacodynamics of atracurium in clinical practice, the steady-state plasma concentration of atracurium for 90% paralysis (Cpss90) was measured in 100 adult patients. Neuromuscular block was maintained at 88%-92% of the control response by adjusting the target concentration being delivered by preprogrammed intravenous atracurium infusion. The Cpss90 was measured empirically from plasma samples taken when the block had been stable for 15 min with no adjustment in the infusion rate for 20 min. To describe how factors influenced the Cpss90 of atracurium, a model was developed by multiple stepwise linear regression analysis. Influencing variables retained in the final model were plasma potassium concentration, intraoperative administration of gentamicin, and premedication with papaveretum and hyoscine. The model predicted that the Cpss90 of atracurium would decrease with decreasing serum potassium according to the relationship log10(Cpss90) = 2.380 + 0.171 x [K mmol/L] (n = 100; ANOVA, P < 0.001). Intraoperative administration of gentamicin modified this relationship resulting in a 25.1% decrease in the predicted Cpss90 (n = 15; ANOVA, P < 0.001). Premedication with papaveretum and hyoscine also modified this relationship resulting in a 21.2% decrease in predicted Cpss90 (n = 30; ANOVA, P < 0.001). The model predicted that administration of both would decrease the Cpss90 by 41.0%. Patients aged > or = 70 yr had a slight, but statistically insignificant, increase in the Cpss90 compared to younger adult patients. No other factor was found to influence the Cpss90, including patient sex, body fluid, and other drugs administered in the perioperative period, including calcium channel antagonists and ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498668 TI - Effect of body build on the clearance of atracurium: implication for drug dosing. AB - To determine factors that influenced the clearance (Cl) of atracurium, 80 adult patients of varying body build were given an atracurium infusion according to a predetermined profile, which was scaled by lean body mass (LBM). Cl was estimated at 50-60 min by the constant infusion rate required to maintain the steady-state plasma concentrations. The efficacy of scaling the absolute Cl estimate by body build variables, in which the absolute Cl estimate is divided by the body build variable to achieve similar scaled estimates in all patients, was assessed by the bias and precision of the individual scaled Cl estimates to those in patients with a "normal" body build (23%-27% body fat). The efficacy of scaling the dose of atracurium by differing body build variables to achieve similar plasma concentrations was also assessed by bias and precision, in which the plasma concentrations from an infusion scaled by other body build variables were generated by linear simulation. Body size, as quantified by LBM, total body mass (TBW), height, and body surface area, had a significant influence on Cl, with the effect best described by LBM (respective R2, 0.487, 0.368, 0.265, 0.445). No other factors could be identified, including blood pH, serum creatinine, and drugs given during the peroperative period. The efficacy of scaling Cl by TBW (absolute Cl estimate divided by patient TBW) to achieve similar estimates in all patients was poor; Cl.TBW estimates varied inversely with patient body fat content and resulted in obese patients having smaller estimates, a mean bias of 29%, compared with those in patients with a normal body build (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498669 TI - Electrical stimulation as a substitute for the tail clamp in the determination of minimum alveolar concentration. AB - Circumstances may preclude the use of standard stimuli, namely tail clamp or surgical incision, to determine minimum alveolar concentration. In rats anesthesized with isoflurane, an alternative stimulus, electrical currents (10, 15, 20, or 40 V; biphasic pulses of 6.5 ms duration; 50 Hz), gave results comparable to those obtained with the tail clamp and the results did not change with repeated measurements if care was taken to avoid desensitization by exhaustion of a particular set of electrodes. The 40 V stimulation gave slightly higher values (4%; P < 0.006) than tail clamp, but the difference was too small to be of experimental significance. More importantly, the higher voltages produced desensitization after fewer attempts at stimulation. In addition to these results with isoflurane, we found that 15 V stimulation and tail clamp produced comparable minimum alveolar concentration values for halothane and for desflurane. PMID- 8498670 TI - Volatile anesthetic requirements differ in mice selectively bred for sensitivity or resistance to diazepam: implications for the site of anesthesia. AB - One approach to elucidating the general anesthetic target has used genetic selection procedures, wherein animals are bred for sensitivity or resistance to general anesthetics and correlations are sought with a specific neuronal structural or functional defect. For example, murine strains have been developed that are either sensitive or resistant to the obtunding effects of diazepam, as assessed by their ability to maintain balance on a rotating rod. The present study explored whether diazepam-sensitive (DS) and diazepam-resistant (DR) mice might also be similarly divergent in the obtunding response to general anesthetics, by testing the requirements for halothane and enflurane in these strains. Using a carousel enclosed in a chamber, the end-point of loss-of righting reflex was defined. For both anesthetics, the DS groups had a lower median effective dose (ED50, %atm) than did the DR group, and the reductions paralleled diazepam susceptibility. For example, with halothane, the ED50 for the DS group was 0.72 +/- 0.022 (SE); the ED50 for the DR group was 0.87 +/- 0.030 (P < 0.0001). Similar results were obtained with enflurane. Such findings associate an inbred difference in response to diazepam with altered volatile anesthetic requirement, suggesting that these two phenotypes are mediated by a common underlying mechanism. PMID- 8498671 TI - Endotracheal tube cuff pressure increases significantly during anterior cervical fusion with the Caspar instrumentation system. AB - To determine whether endotracheal tube cuff pressure increases significantly with surgical retraction and cervical spine distraction during anterior cervical spine surgery with Caspar instrumentation, we prospectively studied 10 patients undergoing this procedure. The tracheas of all patients were intubated with a Mallinckrodt Hi-Lo endotracheal tube. Tracheal tube cuff pressures measured with a transducer system were 42.4 mm Hg +/- 7.0 mm Hg (SEM) after intubation and cuff inflation. Air was removed from the endotracheal tube cuff until the trachea was just barely sealed at a cuff pressure of 15.2 mm Hg +/- 1.6 mm Hg. The endotracheal tube cuff pressure was readjusted to "just-seal" pressure before the surgeons introduced the Caspar instrumentation. The cuff pressure with traction and distraction was 43.2 mm Hg +/- 5.0 mm Hg. This pressure was significantly increased from the "just-seal" pressure, and from the cuff pressure after instrumentation was discontinued (9.8 mm Hg +/- 2.3 mm Hg). We conclude that anterior cervical spine surgery with Caspar instrumentation is associated with a significant increase in endotracheal tube cuff pressure. PMID- 8498672 TI - Nitrous oxide causes myocardial ischemia when added to propofol in the compromised canine myocardium. AB - We sought to determine the influence of nitrous oxide on the compromised heart during propofol anesthesia. This study investigated the cardiovascular effects of the combination propofol and nitrous oxide (N2O). Seven beagles were monitored to measure global and regional left ventricular function. Recordings both before and after critical constriction (CC) of the left anterior descending coronary artery (LAD) were performed after propofol, 300 micrograms.kg-1.min-1, and 10 min after exposure to and discontinuation of 67% N2O. Data were analyzed with ANOVA for repeated measures at 95% confidence level. In the absence of CC, N2O caused moderate, reversible hemodynamic depression (LVdP/dtmax, -13.8%; cardiac output, 17.2%; LAD coronary blood flow, -10.9%) and no regional dysfunction. After CC global hemodynamic depression was of similar magnitude (LVdP/dtmax, -19.9%; cardiac output, -9.2%; stroke volume, -9.2%) but did not recover completely. Systolic shortening in the compromised area decreased (-30.3%) and postsystolic shortening developed to represent 20.3% of total shortening. Despite only moderate hemodynamic depression, 67% N2O causes substantial regional dysfunction in compromised myocardium when added to propofol. PMID- 8498673 TI - Effects of sevoflurane, isoflurane, and halothane on mechanical and electrophysiologic properties of canine myocardium. AB - We studied the effects of sevoflurane on contraction and membrane potentials in isolated canine ventricular muscle strips. Sevoflurane (> 0.5%) depressed electrically induced contraction in a dose-dependent manner. Moreover, sevoflurane did not show stimulation frequency-dependent depression in contraction as shown with local anesthetics. The inhibitory effect was more pronounced in high-K+ Tyrode's solution than in normal Tyrode's solution, suggesting that sevoflurane may inhibit transmembrane Ca2+ influx. In contrast, isoflurane and halothane were equally effective in depressing electrically induced contractions in normal and high-K+ Tyrode's solution. In electrophysiologic experiments, sevoflurane at higher concentrations (> 2.0%) depressed both overshoot and the plateau phase of the action potentials. These depressant effects were more pronounced in high-K+ Tyrode's solution. Resting membrane potential was not affected by sevoflurane. We conclude that depression of myocardial contractility by sevoflurane may be due to a block of the transmembrane calcium influx. PMID- 8498674 TI - Plasma inorganic fluoride levels with sevoflurane anesthesia in morbidly obese and nonobese patients. AB - Administration of several of the inhaled anesthetics result in plasma inorganic fluoride concentrations that are higher in obese compared to nonobese patients. Sevoflurane, a new inhaled anesthetic, is metabolized to inorganic fluoride; however, plasma inorganic fluoride levels with sevoflurane anesthesia in obese subjects have not been evaluated. We studied plasma inorganic fluoride concentrations during and after sevoflurane surgical anesthesia in morbidly obese (n = 13, body mass index > 35) and nonobese (n = 10) patients. Sevoflurane anesthesia in 60% nitrous oxide/40% oxygen was administered with a semiclosed circle absorption system. Mean anesthetic duration was 1.4 minimum alveolar anesthetic concentration (MAC) hours (sevoflurane MAC = 2.05%) for both groups. Pre- and postoperative blood urea nitrogen, creatinine, and liver function tests were evaluated. Venous blood samples were obtained during and after anesthesia for plasma inorganic fluoride analysis. In six morbidly obese and nonobese patients arterial blood samples were obtained during and after sevoflurane anesthesia for determining sevoflurane blood concentration. Plasma fluoride concentrations during and after anesthesia did not differ between morbidly obese and non-obese groups. Peak plasma inorganic fluoride ion concentrations were 30 +/- 2 mumol/L (mean +/- SEM) in obese and 28 +/- 2 mumol/L in nonobese patients 1 h after discontinuing anesthesia. The hourly rate of change of fluoride ion concentration in plasma during anesthesia was similar between the groups. The maximal recorded plasma fluoride concentrations were 49 mumol/L in an obese patient and 42 mumol/L in a nonobese patient. Pre- and postoperative hepatic and renal tests did not differ significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498675 TI - The new Tec6 desflurane vaporizer. AB - The Tec 6 vaporizer is an electrically heated, thermostatically controlled, constant temperature, pressurized, electromechanically coupled dual circuit, gas/vapor blender. The pressure in the vapor circuit is electronically regulated to equal the pressure in the fresh gas circuit. At a constant fresh gas flowrate, the operator regulates vapor flow with a conventional concentration control dial. When the fresh gas flowrate increases, the working pressure increases proportionally. At a specific dial setting at different fresh gas flowrates, vaporizer output is constant because the amount of flow through each circuit is proportional. Independent confirmation of vaporizer performance and design characteristics awaits vaporizer availability. PMID- 8498676 TI - Anesthetic implications of adults with congenital heart disease. AB - In adults with congenital heart disease who are confronted with noncardiac surgery, perioperative risks can be reduced, often appreciably, when problems inherent to this patient population are anticipated. The first necessity is to clarify the diagnosis and to be certain that appropriate information is obtained from a cardiologist with adequate knowledge of congenital heart disease in adults. Physiology and anatomy can vary significantly among patients who superficially carry identical diagnoses and would seem to fit under the same rubric. Elective noncardiac surgery should be preceded by clinical cardiovascular assessment, including reviewing clinical and laboratory data and securing necessary diagnostic studies. Preoperative assessment should be performed far enough in advance of the anticipated surgery to allow for critical assessment of the data. Appropriate cardiovascular laboratory studies to be obtained or reviewed include electrocardiograms, chest radiographs, echocardiograms, and cardiac catheterization data (which may include specialized intracardiac electrophysiologic testing). Congenital heart disease in adults is a new and evolving area of special interest and expertise in cardiovascular medicine. Multidisciplinary centers for the care of these patients are being developed. The 22nd Bethesda Conference recommended that these centers include anesthesiologists with special expertise in managing patients with congenital heart disease among their consultants. These anesthesiologists can function either as attending anesthesiologists when patients require noncardiac surgery, or as consultants and resource individuals to other anesthesiologists. Adults with congenital heart disease may present with age-related acquired cardiovascular and noncardiovascular disorders in addition to postoperative cardiac residua and sequelae, all of which require meticulous preoperative planning and consultation before noncardiac surgery is performed. We recommend that, particularly in larger departments of anesthesiology, select members of the department serve as consultants to anesthesiologists and to other members of the medical staff for these cases, especially when large numbers of adults with congenital heart disease are to be treated. PMID- 8498677 TI - Temperature maintenance during prolonged thoracoabdominal aneurysm repair by a simple heat exchanger in a centrifugal perfusion circuit. PMID- 8498678 TI - Splenic rupture after electroconvulsive therapy. PMID- 8498679 TI - Anesthetic management of a patient with factor XI deficiency and factor XI inhibitor undergoing a cesarean section. PMID- 8498680 TI - An unusual case of epidural failure. PMID- 8498681 TI - Desmopressin and DDAVP. PMID- 8498682 TI - How painful is insertion of a spinal needle? PMID- 8498683 TI - Acute basilic vein thrombosis associated with an anesthetic for craniotomy. PMID- 8498684 TI - Severe acute normovolemic hemodilution and survival. PMID- 8498685 TI - Enhancing limited intravenous access. PMID- 8498686 TI - Difficult ventilation caused by profuse hemorrhage after dislodging a tooth. PMID- 8498687 TI - Double-lumen endobronchial tube intubation using a retrograde wire technique. PMID- 8498688 TI - Is the internal jugular vein cannulated during insertion or withdrawal of the needle during central venous cannulation? PMID- 8498689 TI - A complication of fiberoptic intubation. PMID- 8498690 TI - Difficulty with the nonskiving epidural needle. PMID- 8498691 TI - Headache after spinal anesthesia for cesarean section: a comparison of the 27 gauge Quincke and 24-gauge Sprotte needles. PMID- 8498692 TI - Venous O2 saturation reflects the balance between supply and demand of oxygen. PMID- 8498693 TI - Epidural halothane vapor: a new way for an old anesthetic? PMID- 8498694 TI - Job analysis 1992: infection control practitioner. AB - The Certification Board of Infection Control directed its Research Subcommittee to compose a Job Analysis Committee in 1991. This 9-member Job Analysis Committee, in collaboration with Applied Measurement Professionals, Inc., conducted a job analysis of ICPs during 1992. The reassessment of the previous Certification Board of Infection Control task analysis, formation of a job analysis survey tool, and the actual job-analysis process and its results are described in this article. The previous and newly revised test specification outlines are compared. The national Certification Examination for Infection Control for November 1993 will reflect the efforts of this endeavor. PMID- 8498695 TI - Nosocomial infections in pediatric patients: a prevalence study in Spanish hospitals. EPINE Working Group. AB - BACKGROUND: The magnitude of the problem of nosocomial infection in children has never been studied in Spain. METHODS: In 1990, a nationwide cross-sectional study was conducted to determine the prevalence of nosocomial infection and associated risk factors. RESULTS: Among 38,489 patients surveyed, 4081 were pediatric patients. Three hundred forty-five patients (8.4%) had active nosocomial infection at the time of the survey. Pediatric intensive care units (29.7%), hematology (23%), and special units (22%) showed the highest rates. Infections were most common in patients younger than 1 year (prevalence, 12.3%). Frequencies of nosocomial infection by site were as follows: bloodstream, 22.1%; urinary tract, 13.1%; lower respiratory tract, 12.3%; postoperative wound, 8%; gastrointestinal tract, 7.6%; skin, 6.5%; eye, 5.8%; and others 24.6%. The factors most closely associated with a higher prevalence of nosocomial infection in pediatrics were as follows: age younger than 1 year, surgery, moderate and severe baseline risk, number of diagnoses, and all categories of extrinsic risk factors. The most frequent etiologic agents were gram-positive bacteria (45.8%). CONCLUSIONS: Although the overall prevalence is at an acceptable level, future efforts should be focused on developing more effective prevention strategies in specific areas. PMID- 8498696 TI - Sputum quality: can you tell by looking? AB - BACKGROUND: Nurses are responsible for the collection of sputum samples for culture in most institutions, yet they receive little formal training on what a good specimen looks like. METHODS: Three hundred thirty-three consecutively collected expectorated sputum samples and tracheal aspirates were examined to determine the relationship of macroscopic specimen appearance (watery, mucoid, mucopurulent) to specimen quality (good, fair, poor). RESULTS: Of the expectorated sputum samples, 21% were watery, 65% were mucoid, and 14% were mucopurulent. Sixty-five percent of the expectorated sputum samples were good or fair, regardless of appearance. Eighty-seven percent of mucopurulent expectorated sputum samples were good or fair. In the remaining nonmucopurulent specimens, however, there were no predictable markers of specimen quality. CONCLUSIONS: The only specimens that were predictably good were those that were mucopurulent yellow, yellow, or tracheal aspirates. PMID- 8498697 TI - Higher overall nosocomial infection rate because of increased attack rate of methicillin-resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus has become a frequent cause of hospital-acquired infectious disease. However, the impact of methicillin resistant S. aureus on the overall nosocomial infection rate has not been clearly defined. METHODS: The University of Alabama at Birmingham Hospital is a tertiary care facility and participant in the National Nosocomial Infections Surveillance system. Prospective, hospital-wide surveillance for nosocomial infections was conducted for 8 months per year during 1986 through 1991. RESULTS: The total nosocomial infection rate increased from 4.5% in 1987 to 5.9% in 1990. This was temporally associated with a rise in the attack rate of methicillin-resistant S. aureus from 0% to 0.4%. The remainder of the increase was caused by other gram positive microorganisms, including methicillin-sensitive S. aureus. We identified methicillin-resistant S. aureus most commonly in the surgical intensive care unit and as a cause of lower respiratory tract infections. In contrast, methicillin sensitive S. aureus was most frequently found in the neurologic intensive care unit and as the etiologic agent of surgical wound infections. CONCLUSIONS: Methicillin-resistant S. aureus has become a common nosocomial pathogen. There has been no decrease in the attack rate of methicillin-sensitive S. aureus or other gram-positive cocci. The total nosocomial infection rate has increased as a result equally of the emergence of methicillin-resistant S. aureus and of the renewed activity of other gram-positive pathogens. Methicillin-resistant S. aureus has added to the overall burden of nosocomial infectious disease. PMID- 8498698 TI - Stress distributions in the maxillary complex from orthopedic headgear forces. AB - The present study was conducted to investigate stress distributions in the maxillary complex from headgear forces by means of three-dimensional finite element analysis. A posteriorly-directed force of 1.0 Kgf was applied to the maxillary first molars in the directions parallel and 30 degrees inferior to the occlusal plane. In the lower regions resisting posterior displacement of the complex, large normal and shear stresses were observed. Meanwhile, the regions resisting upward displacement experienced larger than normal stresses. A downward force produced slightly larger stresses than a parallel force and varied the nature of stresses from compressive to tensile or vice versa in the temporozygomatic suture. Thus, the stress distributions in the sutures varied according to their anatomic locations relative to force directions. The maxillary complex exhibits postero-inferior displacement with clockwise rotation from the horizontal headgear force. This becomes more prominent as the direction of force becomes more inferior. PMID- 8498699 TI - Evaluation of the vertical forces generated by the cervical biteplate facebow. AB - The biteplate facebow has been recommended for use in the correction of Class II malocclusions with deep overbites. This facebow is similar in design to the conventional cervical facebow with the addition of an inner bow metal plate. The plate presses against the maxillary incisors and prevents the patient from fully closing, thus acting as a biteplate. A test apparatus was constructed to simulate the force system present during application of the facebow. In this study, high resolution force transducers were used to measure the intrusive forces on the maxillary and mandibular incisors. Static force analysis techniques were then used to calculate the vertical force component of the first molars. Analyses were performed using a wide range of relative bow angles, neck strap tensions of 200 grams and 400 grams, and various mandibular incisor occluding forces. The molar eruptive forces of the biteplate facebow are found to exceed those of the standard cervical facebow by a low of 158% to a high of 537%, depending on the neck strap tension and the inner bow/outer bow angle. While the intrusive forces on the maxillary incisors were excessive, no intrusion is anticipated because the biteplate disarticulates the posterior teeth and the eruption of the unopposed maxillary molars would likely cause the occlusal plane to tip in a counter clockwise direction. Consequently, the overbite correction would be obtained through maxillary molar eruption accompanied by occlusal plane tipping. Before considering use of the biteplate facebow, a patient's anticipated growth pattern, the magnitude of the intrusive forces and the treatment objectives should be evaluated. PMID- 8498700 TI - Physiologic drift of the mandibular dentition following first premolar extractions. AB - A retrospective study of two groups of patients was conducted to evaluate the physiologic drift, or "driftodontics", of the mandibular teeth following the extraction of four first premolars. Group 1 included 32 patients who underwent early extraction in the mixed dentition stage at a mean age of 10.4 years; they were followed for approximately 2.5 years postextraction. Group 2 included 20 patients whose premolars were extracted after the permanent dentition had fully erupted. Their mean age at the time of extraction was 14.2 years, followed by a 0.8 year observation period. Except for the extractions, no other mandibular therapy was rendered. The results show no differences in rates of molar movements between groups. The molar apex moved mesially approximately 0.6 mm/yr; the molar cusp moved mesially approximately 1.2 mm/yr. In contrast, there were marked group differences in movements of the mandibular incisors and canines; rates of change were significantly greater in Group 2 than in Group 1. The canines drifted laterally and distally into the extraction sites while the incisors became more upright over basal bone and less crowded. Incisor irregularity decreased 1.3 mm/yr in Group 1 and 5.5 mm/yr in Group 2. The group differences in amounts of tooth movement were accounted for by changes in incisor crowding. PMID- 8498701 TI - Analyses of craniofacial and dental morphology in monozygotic twins discordant for cleft lip and unilateral cleft lip and palate. AB - The Michigan Cleft Twin Sample data was analyzed in order to investigate dental arch and craniofacial morphology. The present study consisted of 12 monozygotic twins discordant for either cleft lip or unilateral cleft lip and palate. Individuals having CL (repaired) alone did not differ from their unaffected counterparts in dental arch and skeletal morphology. Repaired UCLP subjects were characterized by having a shorter and more posteriorly positioned maxilla. Although reduction of dental arch width as a result of scar contraction following surgery was evident, the effects of scar tissue pull did not affect maxillary basal width. PMID- 8498702 TI - The effects of sterilization on the tensile strength of orthodontic wires. AB - The purpose of this study was to evaluate the effect of sterilization on the tensile strength of 0.016" beta-titanium, nickel titanium and stainless steel wires. Three common methods of sterilization--autoclaving, dry heat and ethylene oxide--were evaluated in three test trials involving zero, one and five sterilization cycles. For each of the test trials, five pieces each of 0.016" TMA, 0.016" Sentalloy and 0.016" Tru-chrome stainless steel wires were sterilized using a standard autoclave. Five other pieces of each of the same wires were sterilized in a dryclave, while an additional five pieces of each of the three wire types were sterilized using ethylene oxide. The ultimate tensile strengths of the wires were then determined using an Instron Universal Testing Machine. The data were compared for statistical differences using analysis of variance. The results showed that dry heat sterilization significantly increased the tensile strength of TMA wires after one cycle, but not after five cycles. Autoclaving and ethylene oxide sterilization did not significantly alter the tensile strength of TMA wires. Dry heat and autoclave sterilization also significantly increased the tensile strength of Sentalloy wires, but the mean strength after five sterilization cycles was not significantly different than after one cycle. Ethylene oxide sterilization of Sentalloy wires did not significantly alter the tensile strengths of that wire. There were no significant differences in the tensile strengths of the stainless steel wires following zero, one or five cycles for any of the sterilization methods. PMID- 8498703 TI - Force generation by orthodontic coil springs. AB - Nickel titanium (NiTi) coil springs are a new development in orthodontics, designed to produce light continuous forces. This study compares the force delivery by NiTi open and closed coil springs during unloading (de-activation) to that provided by comparable stainless steel (SS) springs. Open-coil springs (0.010 x 0.035 inch) were compressed from their initial length of 15 mm to 6 mm and the forces generated with spring recovery recorded. Closed-coil springs (0.009 x 0.035 inch) were distracted from their initial length of 3 mm to 9 mm and the force recorded as the spring recovered. The closed-coil NiTi springs produced light continuous forces of 75-90 g over the distraction range of 6 mm while the open-coil springs produced forces of 55-70 g within the 9 mm compression range. SS springs produced heavier forces, ca. 200 g, for an activation of 1 mm and the generated force increased rapidly as the activation was increased. The findings indicate that NiTi coil springs deliver optimal forces for orthodontic tooth movement over a longer activation range than comparable SS springs. PMID- 8498704 TI - In vivo bonding of orthodontic brackets with glass ionomer cement. AB - The adhesion of orthodontic bracket bases was examined in vivo 24 to 32 hours after bonding with glass ionomer cement (GIC). In contrast to bonding with composite resin, with GIC there is no need to etch the enamel surface of the tooth. Conventional metal brackets with mesh pad, bonded with GIC, showed an average shear bond strength of 3.6 +/- 1.1 MPa, approximately one-fourth the bond strength of composite resin. Fracture sites were found exclusively at the mesh/GIC interface. Bonding between GIC and enamel must, therefore, be stronger than bonding between conventional resin and enamel. An experimental attachment with a modified base, consisting of brass rings 4 mm in diameter with a retention groove, was designed. In these experimental cases, fractures were found at the base/GIC interface and at the enamel/GIC interface. Shear bond strength of the experimental base was as high as 5.8 +/- 1.0 MPa. These values approached those of brackets bonded with composite resin and acid etching. Bond strengths of up the 3 MPa which occur during orthodontic treatment were achieved. Clinical trials with GIC bonding thus seem feasible and are being initiated. PMID- 8498705 TI - The limitations of orthodontic treatment. AB - There is probably nothing in the orthodontist's diagnostic repertoire that will precipitate an adrenaline rush faster than a first examination of a mixed dentition patient who has an obvious skeletal problem. Everyone present in the examination room expects the doctor to manage the problem with some gadget...the same way that produced favorable results for the three playmates in the neighborhood who originated the referral. But intellectually, the clinician knows conventional treatment may not be in this individual's best interest and must intuitively develop a definition of "The Limitation of Orthodontic Treatment." PMID- 8498706 TI - Case report: four permanent second molar extractions. AB - A patient who had earlier undergone four second molar extractions and who demonstrated Class II buccal segments and major incisor crowding was treated with the relatively unusual extraction pattern of maxillary lateral incisors. The treatment resolved the crowding and created Class II buccal segments with maxillary canines substituted for extracted lateral incisors. Favorable tooth anatomy produced an acceptable esthetic result accomplished with a predictable outcome over a reasonable duration of treatment. The sequential panoramic radiographs show evidence of the third molars spontaneously progressing toward positions that may result in their successful substitution for the earlier extracted second molars. A relatively unorthodox treatment plan made possible resolution of a difficult existing clinical situation using relatively routine treatment procedures. PMID- 8498707 TI - Case report TM: early intervention makes nonextraction, nonsurgical treatment possible. AB - An early phase of treatment limited to orthopedic change as well as the elimination of injurious oral habits makes possible a nonextraction, nonsurgical approach to treatment. Although careful timing and excellent cooperation are essential, it is hard to fault the long-term results of this treatment plan. PMID- 8498708 TI - Maxillary canine-first premolar transposition, associated dental anomalies and genetic basis. AB - Maxillary canine-first premolar (Mx.C.P1) transposition, an uncommon dental anomaly involving positional interchange of the two teeth, was studied using a sample of 43 subjects with the abnormality. Data were recorded on sidedness, sex, race, tooth agenesis, and peg-shaped maxillary lateral incisors for each case. Mx.C.P1 transposition occurred bilaterally in nearly one-quarter of the sample and favored female expression (sex ratio, M1:F3.8) and left-side occurrence (61% of unilateral cases). Familial occurrence was noted, as was a predilection for white subjects. Tooth agenesis (excluding third molars) and/or peg-shaped maxillary lateral incisors accompanied Mx.C.P1 transposition in 49% (21) of the subjects, four to ten times the normal rate of occurrence. Data from this study and the analysis of previously published cases provided strong evidence that Mx.C.P1 transposition is a disturbance of tooth order and eruptive position resulting from genetic influences within a multifactorial inheritance model. PMID- 8498709 TI - Construction of a library of bovine genomic fragments enriched in CpG islands. AB - A procedure is described to isolate DNA probes from the bovine genome that are enriched in sites for the so-called rare cutter restriction endonucleases. A collection of SacII (CvCGCGG)-Hin-dIII fragments from bovine sperm was established in the plasmid Bluescript. 180 clones were picked at random and analysed for the presence of inserts with sites for the following rare cutters: EagI, BsshII, NarI, MluI, NruI, NaeI: 70% of the clones contained at least 1 site and 5% contained four different such sites. 22.8% had multiple sites for one or more of the rare cutters tested. Sequence analysis for 16 clones confirmed the cloning of DNA with a G+C content and a proportion of CpG vs GpCs indicative of CpG islands. PMID- 8498710 TI - Biochemical characterization of the bovine genetic kappa-casein C and E variants. AB - Analysis of elution profiles of enzymatic and CNBr digests of kappa-caseins C and E, and sequencing of most relevant peptides allowed the chemical characterization of both genetic variants. They differ from their B and A allelic counterparts by a single substitution, His97/Arg and Gly155/Ser, respectively. Electrophoretic behaviour of the investigated C and E variants was in good agreement with the observed amino acid replacements. PMID- 8498711 TI - Short interspersed nuclear element (SINE) sequences of the Bovidae. AB - DNA sequences from Bovidae (cattle, goats and sheep) in the EMBL nucleotide database contain several short interspersed repeated sequences (SINEs). Three different SINEs have been found: Bov-A2, containing two 115-bp A elements; Bov tA, a tRNA pseudogene coupled to an A element; and Bov-B of 560 bp or less and partially homologous to the A element. Bov-A2, Bov-tA and Bov-B occupy about 1.8%, 1.6% and 0.5%, respectively, of the bovine genome as represented in the nucleotide database. Apart from a tRNA-like sequence in both Bov-tA and the porcine SINEs, there was no similarity with the porcine SINEs. Apparently, the artiodactyle SINEs were established after the divergence leading to the Suidae and Bovidae but before the radiation within these families. Oligonucleotides were designed for a specific amplification of DNA from Bovidae. PMID- 8498712 TI - Use of isoelectric focusing to define major histocompatibility complex class I polymorphism in goats. AB - We have used biochemical methods to extend and improve serological class I typing using a panel of 77 Swiss goats of the Saanen breed, comprising dam-offspring combinations from six half-sib sire families and several unrelated animals. Of these animals class I molecules were precipitated from cell lysates with the mAb B1.1G6 and HC10. Immunoprecipitates were analysed by SDS-PAGE and 1D-IEF. There was a good agreement between class I serological types and IEF banding patterns. We have identified three new class I specificities and subdivided the Be17 specificity. IEF has enabled us to make planned immunizations to produce antisera to the new specificities. New evidence for the expression of a second class I locus product in the Be7 haplotype has been found. PMID- 8498713 TI - Association between the bovine major histocompatibility complex and chronic posterior spinal paresis--a form of ankylosing spondylitis--in Holstein bulls. AB - A highly significant association was found between the bovine MHC class I antigen BoLA-A8 and a form of vertebral osteophytosis/ankylosing spondylitis known as chronic posterior spinal paresis (PSP) in Holstein bulls (P < 0.001). In a population study, restricted to unrelated bulls, BoLA-A8 was significantly associated with PSP (P = 0.0015) with a relative risk of 34.6. In a family study, one PSP bull, BoLA A8/A20, sired 13 offspring. BoLA-A8 was significantly associated with PSP (P = 0.0008). All five PSP sons inherited the A8 allele and the eight healthy sons each inherited the A20 allele. In three other families a complete association of BoLA-A8 and PSP was observed. Lod score analysis, using all available families, indicated a significant linkage between BoLA and PSP (lod score = 6.9). Based on clinical observation, pathology, age/sex predilection, and a strong association with a class I MHC molecule, this inflammatory disease appears analogous to the human condition known as ankylosing spondylitis. PMID- 8498714 TI - Polymorphism of erythrocyte glucosephosphate isomerase in sheep. AB - An electrophoretic analysis of glucosephosphate isomerase (GPI) in seven Italian sheep populations suggests that this locus is more polymorphic than previously supposed. The observed phenotype distributions are in agreement with the hypothesis of the existence of three codominant alleles, GPI*F, GPI*S and GPI*N, GPI*S being the most frequent (0.935 divided by 1.000). PMID- 8498715 TI - A new alpha S1-casein allele in bovine milk and its occurrence in different breeds. AB - A new alpha S1-casein variant (alpha S1-CN F) with a frequency of 0.009 was demonstrated in a genetic resource of German Black and White Cattle by isoelectric focusing in polyacrylamide gels and by polyacrylamide gel electrophoresis under alkaline conditions. alpha S1-CN F was not present either in German Holstein Friesians, which originate from crossing Holstein Friesians with German Black and White Cattle, or in milk samples from eight other breeds in Germany. PMID- 8498716 TI - A highly polymorphic bovine microsatellite locus: BM2113. PMID- 8498717 TI - A porcine polymorphic microsatellite locus (S0031). PMID- 8498718 TI - Polymorphism in an A- and T-rich element in the beta-haemoglobin locus in sheep. PMID- 8498719 TI - Dinucleotide polymorphism at the bovine histamine H1 receptor locus. PMID- 8498720 TI - ILSTS005: a polymorphic bovine microsatellite. PMID- 8498721 TI - ILSTS006: a polymorphic bovine microsatellite. PMID- 8498722 TI - Five polymorphic bovine microsatellites (ILSTS010-014). AB - We report a set of five new bovine microsatellite polymorphisms based on (CA)n repeats. They are highly polymorphic and thus represent valuable markers for genome mapping. PMID- 8498723 TI - How to present data for publication. PMID- 8498724 TI - Genetics of allergy. PMID- 8498725 TI - Wheezing, hypoxia, and dyspnea in a 62-year-old woman. AB - This patient presented with dyspnea, hypoxia, and generalized wheezing; however, her pulmonary function testing did not suggest asthma. Subsequent evaluations for conditions that may mimic asthma were not helpful. An invasive procedure (pulmonary angiogram) was required to diagnose pulmonary embolism, a potentially life threatening but treatable condition. The angiogram was performed despite nondiagnostic ventilation and perfusion scans because of a high index of suspicion for pulmonary embolism. In our patient, observation revealed episodes of sudden tachycardia, dyspnea, and increased wheezing which further raised our suspicion. Because pulmonary emboli can have such protean manifestations, it would be wise to consider pulmonary emboli in any patient with presumed asthma who has symptoms out of proportion to his or her pulmonary function testing and/or is not responding to treatment. PMID- 8498726 TI - One organization or two? The cases for two cooperative, independent societies versus reorganization into one society. The White Paper Committee of the American College of Allergy and Immunology. PMID- 8498727 TI - ACAI Board of Regents position statement on merger. PMID- 8498728 TI - Systemic anaphylaxis from low dose methotrexate. PMID- 8498729 TI - Successful oral acyclovir desensitization. AB - A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy. Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity. Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity. Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens. Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity. This report is an example of acyclovir hypersensitivity and successful oral desensitization. PMID- 8498730 TI - Safety and efficacy of terfenadine/pseudoephedrine versus clemastine/phenylpropanolamine in the treatment of seasonal allergic rhinitis. AB - A double-blind, randomized, placebo-controlled, parallel trial was conducted to compare the efficacy and safety of terfenadine, 60 mg (immediate release)/pseudoephedrine hydrochloride, 120 mg (controlled-release) (T/Ps) and clemastine fumarate, 1.34 mg (immediate-release)/phenylpropanolamine, 75 mg (sustained-release) (C/Ph) in a combination tablet b.i.d. in 178 patients (12-59 years of age) with symptoms of seasonal allergic rhinitis. After seven days of treatment, the total symptom scores recorded in the diaries of 175 patients showed that both therapies had a highly significant overall treatment effect when compared with placebo (P < or = .02). The overall level of improvement, as well as improvement of individual symptoms, was similar with the two therapies. Total symptom scores assigned by physicians to 170 patients showed significant and similar levels of improvement with both therapies when compared with placebo (P < .01). The two therapies were also similar on physicians' evaluations of overall effectiveness. Both therapies relieved most histamine-mediated symptoms as well as nasal congestion, although only T/Ps showed improvement of the latter symptom in both the patients' diaries and physicians' evaluations. Among 178 patients, drowsiness and fatigue occurred more often in the C/Ph group (25% and 11.7% for the two adverse events, respectively) than in the T/Ps group (10.2% and 1.7%, respectively). The incidence of insomnia and dry mouth/nose/throat was higher with T/Ps (23.7% and 11.9%, respectively) than with C/Ph (6.7% and 3.3%, respectively). No serious or unexpected adverse events were reported. These results indicate that T/Ps and C/Ph are both superior to placebo and equally effective in the treatment of symptoms of seasonal allergic rhinitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498731 TI - Myocardial infarction induced by coronary vasospasm after self-administration of epinephrine. AB - A case of a 30-year-old man who developed a myocardial infarction after self administering an Epi-Pen for an episode of idiopathic anaphylaxis is reported. The patient had numerous risk factors for coronary artery disease, and it was suspected that epinephrine-induced coronary spasm caused the infarct. The Epi-Pen Junior may be indicated in such adults with numerous risk factors for coronary artery disease who are at risk for recurrent anaphylaxis. PMID- 8498732 TI - Dyspnea in acute asthma: relationship with other clinical and physiologic variables. AB - This investigation comprised 58 patients (35 men, mean age 61 years) with acute asthma: mean FEV1 35% of the predicted. The dyspnea score (Borg's scale), breathing rate, pulse rate, blood pressure, FEV1, and PEF were measured on arrival and 30, 60, and 150 minutes after bronchodilator treatment. The level of clinical severity was evaluated using Hedstrand's asthma severity scale. The variables that correlated most closely with dyspnea score at arrival were asthma severity score (r = .51 P < .001) and breathing rate (r = .38, P < .01). The measurement of airflow obstruction with the closest correlation to improvement in dyspnea was FEV1 expressed as a percentage of the pretreatment value (r = -.30* after 30 min, r = -.42** after 60 and r = -.34* after 150 minutes, *P < .05, **P < .01). When examining the intraindividual correlation between the change in dyspnea score and FEV1, a correlation coefficient of more than 0.80 was found in 74% of the patients. Of 18 patients with an increase in FEV1 of less than 20% of baseline, 11 had a decrease in dyspnea score in 3 or more categories. We conclude that there is a discrepancy in the treatment of acute asthma between the effect on dyspnea and airflow obstruction, the clinical implication of which remains to be investigated. PMID- 8498733 TI - Small intestinal mucosa IgE plasma cells and specific anti-cow milk IgE in children with cow milk protein intolerance. AB - In a prospective study we looked for the presence of both IgE plasma cells in small bowel mucosa and specific serum IgE antibodies to cow milk in children suspected of cow milk protein intolerance. Thirty-one children with complaints possibly due to cow milk intolerance were submitted to two consecutive cow milk elimination/challenge tests. The diagnosis of cow milk protein intolerance was confirmed in 16 of our 31 patients on the basis of two positive elimination/challenge tests. IgE plasma cells were found in nine of 16 patients with proven cow milk protein intolerance and in only one of the 15 patients without cow milk protein intolerance (p < .01). The RAST for cow milk was positive in six of 16 infants with cow milk protein intolerance and in two of the 15 other infants. Serum IgE level was of no value for the diagnosis of cow milk protein intolerance. Neither of these diagnostic procedures was sensitive enough to be used as a screening test for cow milk protein intolerance. Furthermore, the relationship between specific IgE antibodies for cow milk and the presence of mucosal IgE plasma cells was poor: five of nine infants with cow milk protein intolerance and the presence of mucosal IgE plasma cells had negative RASTs for cow milk. PMID- 8498734 TI - Reproducibility of allergen-induced asthma and associated increase in bronchial responsiveness to methacholine in asthmatic children. AB - We studied the reproducibility of early (EAR) and late (LAR) asthmatic response to allergen challenge in 13 asthmatic children (four girls, age range: 10 to 17 years) sensitized only to Dermatophagoides pteronyssinus (Dp). Further, changes in bronchial responsiveness to inhaled methacholine following LAR were examined by measuring PC20FEV1 methacholine after 24, 48, and 72 hours. We carried out two carefully controlled allergen challenges with the same allergen dose within 4 to 6 weeks, at least 3 weeks apart, in each subject. On each study day, a bronchial challenge with methacholine was performed before and at different intervals after LAR. We found that EAR (maximal % fall in FEV1 within the 1st hour) measured on two different days was highly reproducible (37.8% +/- 8.9 and 38.7% +/- 12.1; CR: 12.1; Ri: 0.92; CoV: 15.1). Late asthmatic response (maximal % fall in FEV1 between 2nd and 12th hour) was also highly reproducible (47.5% +/- 12.4 and 46.1% +/- 13.4; CR: 10.1; Ri: 0.96; CoV: 10.1). All patients showed increases in nonspecific bronchial responsiveness to methacholine after LAR. Geometric mean PC20 M measured before the two allergen challenges was 0.609 mg/mL and 0.620 mg/mL, respectively. These values significantly decreased 24, 48, and 72 hours after LAR (after 1st allergen challenge: 0.086, 0.116, and 0.295 mg/mL; after 2nd allergen challenge: 0.075, 0.141, and 0.263 mg/mL). Ratio changes in PC20 methacholine (pre-allergen PC20 methacholine/lowest postallergen PC20) were highly reproducible (Ri: 0.95). We concluded that bronchial response to allergen challenge and the associated increase in responsiveness to methacholine are highly reproducible in well selected asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498735 TI - IgG deficiency in adults with recurrent respiratory infections. AB - Total IgA, IgM, IgG, and IgG subclasses were measured in 136 consecutive adults with recurrent respiratory infections. Sinus and chest radiographs were also obtained. IgG antibodies to H. influenzae and tetanus toxoid were determined in 27 immunodeficient subjects. Fifty-eight of the 136 were deficient in some immunoglobulin isotype, three in IgA, three in IgM, and 52 in total IgG or one or more IgG subclasses. The most common IgG deficiencies were single IgG subclass deficiencies, particularly IgG3 or IgG4, and a mild decrease in total IgG (between 450 and 650 mg/dL). In 21/27 subjects with IgG deficiency, the response to booster immunization was blunted, even when IgG1 and IgG2 were normal. Thirty eight patients were smokers, 37 being > 40 years of age at the onset of respiratory infections. Twenty patients were nonsmokers, 19 being < 40 years of age at the onset. In conclusion, adults with recurrent respiratory infections frequently have some variant of IgG deficiency, often associated with a functional impairment of specific antibody response. Smoking may represent a risk factor for IgG deficiency in adults. PMID- 8498736 TI - Relationships between asthma mortality and treatment. PMID- 8498737 TI - Thresholds for aspirin intolerance. PMID- 8498738 TI - Vertical ground reaction force distribution during experimentally induced acute synovitis in dogs. AB - The pattern of vertical ground reaction force redistribution among limbs during episodes of acute synovitis of the stifle in 12 mixed-breed dogs was investigated as an adjunct to a blinded nonsteroidal anti-inflammatory drug efficacy study. Without regard to drug efficacy groupings, the redistribution of vertical forces before and during the acute synovitis episode was evaluated by analysis of gait, using a force platform. Acute synovitis was induced by intrasynovial injection of sodium urate crystals. Simultaneously, each dog was given 1 of 4 treatment regimens, including IV injection of sterile saline solution (as a negative control), phenylbutazone (as a positive control), or 1 of 2 proprietary nonsteroidal anti-inflammatory drugs. Postinjection analyses took place at 2, 4, 8, 12, 24, and 36 hours. The peak vertical force redistribution in the 3 untreated limbs of the dogs was described. The greatest redistribution was observed 4 hours after substance injection when the synovitis was clinically at maximum. Thereafter, there was steady improvement and the dogs had a clinically normal gait 24 hours after substance injection. During synovitis, peak vertical force increased in the contralateral hind limb. During the more severe synovitis episodes, force was decreased in both forelimbs. There was good correlation between severity of lameness and peak vertical force response in the contralateral hind limb. Results of the study indicate that the untreated limbs of the same animal should not be used as a control during acute lameness studies. PMID- 8498739 TI - Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglandin E2 values in horses. AB - In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyzed for cell counts, protein concentration, cytologic variables, and tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) values. Tumor necrosis factor and IL-6 activities and WBC count were also measured in blood. To monitor local inflammation, skin temperature of each carpus was imaged, using a thermographic scanner prior to each sample collection time. Horses had minimal systemic effects. Mean (+/- SEM) rectal temperature increased significantly to 39.02 +/- 0.15 C only at PIH 18 after intra-articular injection of LPS. One horse had signs of mild depression from PIH 7 to 18, but its vital signs did not change appreciably. Each horse had mild signs of discomfort in the LPS-injected limb from PIH 1 to 3 until PIH 8 to 10. Mean peak surface temperature of the LPS injected carpi was significantly higher than that of control carpi from PIH 8 to 144 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498740 TI - Prevalence of mycoplasmal and ureaplasmal recovery from tracheobronchial lavages and prevalence of mycoplasmal recovery from pharyngeal swab specimens in dogs with or without pulmonary disease. AB - The prevalence of mycoplasmal and ureaplasmal recovery from tracheobronchial lavage specimens and the prevalence of mycoplasmal recovery from pharyngeal swab specimens from dogs with (n = 38) or without (n = 26) pulmonary disease were determined. Similar mycoplasmal recovery rates were found for tracheobronchial lavage specimens from dogs > or = 1 year old with (21%) or without (25%) pulmonary disease. Prevalence of mycoplasmal recovery from tracheobronchial lavages was significantly associated with pulmonary disease among dogs < 1 year old (P = 0.04), and with dogs that had concurrent Bordetella (P = 0.006) and Streptococcus (P = 0.05) isolations. Among dogs with pulmonary disease, mycoplasmas were significantly (P = 0.02) more prevalent in dogs with septic inflammation than in dogs with nonseptic inflammation of the tracheobronchial tree. Ureaplasmas were only isolated from a tracheobronchial lavage specimen of 1 dog with pulmonary disease and from none of the dogs without pulmonary disease. Most dogs with (84%) and all dogs without pulmonary disease had mycoplasmas isolated from the pharynx. Seemingly, mycoplasmas are part of the normal pharyngeal flora of most dogs and normal inhabitants of the lower airway in about a fifth to a fourth of the canine population > or = 1 year old. Dogs < 1 year old with pulmonary disease and dogs with concurrent Bordetella or tracheobronchial streptococcal isolations may be more susceptible to mycoplasmal colonization of the lower airways. Seemingly, ureaplasmas are rarely associated with pulmonary disease, and are not normal inhabitants of the trachea and bronchi of dogs. PMID- 8498741 TI - Effect of Corynebacterium pseudotuberculosis phospholipase D on viability and chemotactic responses of ovine neutrophils. AB - Corynebacterium pseudotuberculosis phospholipase D (PLD) significantly affected viability of ovine neutrophils after 24 hours' exposure. This effect was more marked in cells that ingested PLD emulsified in oil. Treatment of neutrophils with PLD significantly (P < 0.05) reduced the ability of these cells to migrate toward activated sheep serum. The PLD was not chemotactic, but it activated normal sheep serum, producing factors that were chemotactic for neutrophils. PMID- 8498742 TI - Association between clinical lameness and Borrelia burgdorferi antibody in dairy cows. AB - Results of an ELISA, indirect fluorescent antibody (IFA) test, and immunoblot analysis (western blotting) for antibody to Borrelia burgdorferi in a sample of 216 lactating dairy cows were compared. The microscopic microtitration agglutination test for antibody to 6 serovars of Leptospira interrogans was also performed to evaluate possible cross-reactivity between B burgdorferi and L interrogans. Using western blotting as the standard test against which the ELISA and IFA test were compared, the ELISA had greater sensitivity (50% in summer and 38% in spring) with similar specificity (83 and 82%), compared with the IFA test (sensitivity, 6 and 5%; specificity, 90 and 83%). In addition, seropositivity to B burgdorferi, using the ELISA, was not found to be associated with seropositivity to L interrogans serovars. A matched case-control study evaluating the association between clinical lameness and antibody to B burgdorferi was performed in lactating dairy cows of 17 Minnesota and Wisconsin herds. Sera from case and control cows matched by herd, parity, and stage of lactation were evaluated, using an ELISA for B burgdorferi antibody during 2 seasons. High B burgdorferi antibody values were associated with clinical lameness in dairy cows (P = 0.006 in summer and P = 0.04 in spring). PMID- 8498743 TI - Controlled tests of activity of several antiparasitic compounds against natural infections of Haemonchus contortus and other helminths in lambs from a flock established in 1962. AB - Antiparasitic activity of several compounds was evaluated over a long period (about 25 years) in the same flock of sheep. Haemonchus contortus was of special interest, including its relation to drug resistance, especially to thiabendazole and other benzimidazoles, in addition to phenothiazine. Eleven compounds were evaluated in 15 controlled tests, done between 1966 and 1989 in naturally infected lambs (n = 145) born and raised on the same pasture. Sheep were first placed on the pasture in 1962, and a few more were added thereafter. Internal parasites in these sheep were classified in 3 general categories: indeterminate exposure to parasiticides; H contortus, resistant to thiabendazole; and H contortus, resistant to phenothiazine. The parasitic infections probably became more homogeneous after several years because of few introductions of outside sheep after initial establishment of the flock. Activity against naturally acquired internal helminths was evaluated for cambendazole (CBZ: dosage, 20 mg/kg of body weight), fenbendazole (FBZ: 5 or 7.5 mg/kg), mebendazole (MBZ: 10 mg/kg); oxfendazole (OFZ: 3.5 or 10 mg/kg), oxibendazole (OBZ: 10 mg/kg); parbendazole (PBZ: 15 mg/kg), phenothiazine (PTZ: 550 mg/kg); pyrantel pamoate (PRT: 25 mg base/kg), tetramizole (TET: 15 mg/kg); thiabendazole (TBZ: 30 or 44 mg/kg), and trichlorfon (TCF: 100 mg/kg). Thiabendazole was used more often (9 tests) than the other compounds. Thiabendazole was more active against mature H contortus in later years than when first used in 1966, although it was never 100% effective. Efficacy against immature H contortus for TBZ did not exceed 86%. Activity against immature and mature stages of this parasite was good overall for the other benzimidazoles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498744 TI - Intrastadial and interstadial transmission of Anaplasma marginale by Boophilus annulatus ticks in cattle. AB - The 1-host tick Boophilus annulatus was found to transmit anaplasmosis in cattle transstadially. Anaplasma marginale was invariably transmitted when ticks that had been pulled off Anaplasma-infected calves either after 7 days (as fully engorged larvae) or after 14 to 15 days (as fully engorged nymphs) were transferred within 4 days to susceptible calves. Three morphologically different A marginale isolates, 1 round (tailless) and 2 with different types of appendages (tailed) were transmitted by the ticks. These findings might explain the overlap of the geographic distribution of the disease and that of Boophilus spp in some areas of the world. PMID- 8498745 TI - Detection of Toxoplasma gondii antigen-containing immune complexes in the serum of cats. AB - Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii antigen containing IgM immune complexes (T gondii-specific IgM-IC) and IgG immune complexes (T gondii-specific IgG-IC) in the serum of cats were developed. Serum from clinically ill, naturally infected cats; healthy, naturally infected cats; and healthy cats experimentally inoculated with T gondii was assayed. All combinations of T gondii-specific IgM, IgG, antigens, IgM-IC, and IgG-IC were detected in naturally infected and experimentally infected cats. Clinically ill cats and cats with ocular signs of toxoplasmosis were more likely than healthy cats to have T gondii-specific IC in serum. It was concluded that T gondii specific IC form in the serum of cats, may play a role in clinical disease development, and affect the results of T gondii-specific IgM, IgG, and antigen serologic assays. PMID- 8498746 TI - Detection of Akabane viral antigen and immunoglobulin-containing cells in ovine fetuses by use of immunoperoxidase staining. AB - Akabane virus (AKV) strain OBE-1 was inoculated IV into 17 pregnant sheep. Ten fetuses infected at 29 to 45 days of gestation and examined 29 to 30 days later had AKV antigen in the following groups of cells: neuroglial cells in the brain and spinal cord, ganglion cells in the cranial and abdominal ganglia, layer of ganglion cells in the retina, ganglion cells (Auerbach's plexus) in small intestine, hepatocytes, cells in the arterial wall of mesenteric membrane, and trophoblast cells in the placenta. Prior to detection of circulating virus neutralizing antibody, immunoglobulin-containing cells were found initially at 59 days of gestation in the peripheral portion of white pulp tissue in the spleen. After that, numbers of immunoglobulin-containing cells gradually increased. These results indicated that AKV may have strong affinity for neuronal and ganglional cells in infected fetuses and immunoglobulin-containing cells might be considered the earliest immunologic response to AKV replication in the fetus. PMID- 8498747 TI - Immunocytochemical localization of type A influenza virus nucleoprotein in chicken kidney, using freeze substitution technique for tissue fixation. AB - Kidney tissues were removed from euthanatized mature White Leghorn chickens 4 days after IV inoculation with type A influenza virus. The kidney tissues were then fixed at -70 C, using a freeze substitution technique. Type A influenza virus nucleoprotein was readily detected in the nuclei and cytoplasm of the proximal and distal tubular epithelial cells by immunocytochemistry, and the sharpness of the immunomarker in the cells indicated minimal antigen migration during fixation and tissue section preparation. This tissue fixation technique also resulted in good preservation of cellular morphology. The freeze substitution technique of tissue fixation is an excellent alternative to cryostat cut acetone-fixed tissue sections or conventional chemical fixation of paraffin embedded tissues for in situ immunocytochemical localization of type A influenza virus nucleoprotein antigen. PMID- 8498748 TI - Neuromuscular blockade by use of atracurium in anesthetized llamas. AB - Anesthesia was induced in 8 healthy llamas by administration of guaifenesin and ketamine, and was maintained with halothane in oxygen. On 2 separate experimental days, atracurium was given to induce 95 to 99% reduction of evoked hind limb digital extensor tension (twitch). For the first part of the study, atracurium was given IV as repeat boluses, with muscle twitch strength being allowed to return without intervention to 75% of baseline after each bolus before the subsequent bolus was given. A total of 5 bolus doses of atracurium was given. For the first bolus, 0.15 mg/kg of body weight IV, and for subsequent boluses, 0.08 mg/kg, induced desired relaxation. Onset of relaxation was slightly more rapid for repeat, compared with initial, bolus. Duration of relaxation and recovery time were similar to initial and repeat doses. Maximal twitch reduction was observed in 4 +/- 0.2 minutes (mean +/- SEM). Duration from maximal twitch reduction to 10% recovery was 6.3 +/- 0.4 minutes. Twitch recovery from 10 to 50% of baseline took 11.6 +/- 0.6 minutes. Twitch recovery from 10 to 75% recovery took 19.5 +/- 1.1 minutes. Recovery from 10% twitch to 50% fade took 12.8 +/- 0.5 minutes. Fade at 50% recovery of twitch was 39 +/- 0.02%. Significant (P < 0.05) animal-to-animal variation was observed in twitch recovery times. For the second part of the study, atracurium was initially given IV as a 0.15-mg/kg bolus, followed by infusion for 1 to 2 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498749 TI - Pharmacokinetics of ibuprofen in lactating dairy goats. AB - Pharmacokinetic variables of ibuprofen were studied in 6 adult lactating dairy goats after single administration of the drug (14 and 25 mg/kg of body weight, IV, and 50 and 100 mg/kg, PO). Each of the goats was given all doses, with a minimum of 1 week between doses. Ibuprofen concentration in serum was analyzed by use of high-performance liquid chromatography. The lower limit of detection for the ibuprofen assay was 50 ng/ml. Ibuprofen pharmacokinetic variables after IV administration best fit an open two-compartment model. Geometric mean (range) volume of distribution at steady state was 0.16 (0.11 to 0.19) and 0.17 (0.15 to 0.19) L/kg, and terminal half-life was 1.08 (0.79 to 1.70) and 1.27 (1.03 to 1.88) hours, for ibuprofen dosages of 14 and 25 mg/kg, respectively. After 50 and 100 mg/kg administered orally, bioavailability was 90.8 and 106%, respectively. Area under the curve increased linearly with dose administered. Adverse effects were not observed in goats given ibuprofen. PMID- 8498750 TI - Effects of long-term administration of clenbuterol in mature female rats. AB - Female Sprague-Dawley rats were treated IM with 0, 2.5, 25, and 50 micrograms of clenbuterol HCl/kg of body weight/d for 21 days. In all treated rats, significant increase in body weight gain (P < 0.05) and improvement in feed conversion ratio (P < 0.05) were recorded. Hydrometra was observed in the uterus of treated rats, and histologically, it was possible to see dilatation of luminal glands and ovarian alterations. Clenbuterol treatment induced significant (P < 0.05) increase in uterine estrogen receptor concentration of rats treated with the 2 higher doses. Treatment apparently failed to enhance the rate of oxidative and conjugative biotransformations, except for glucuronidation of p-nitrophenol (P < 0.05). On the basis of the data obtained, we could affirm that high doses of clenbuterol affect the female reproductive system of rats inducing, almost in part, estrogen-like modifications, but probably by a different mechanism of action correlated to intense adrenergic stimulation. PMID- 8498751 TI - Effect of a specific platelet-activating factor antagonist on cardiovascular and peripheral cellular responses to colonic ischemia and reperfusion in anesthetized ponies. AB - The role of platelet-activating factor in mediating the cardiovascular and peripheral cellular responses to large-colon ischemia and reperfusion, was explored in anesthetized ponies. A specific platelet-activating factor (PAF) antagonist (WEB 2086) was administered to a group of 6 ponies, and another 6 ponies (controls) were given an equivalent volume of saline solution, prior to 1 hour of large-colon torsion. After correction of the torsion, ponies were monitored during the reperfusion period. Significant (P < 0.05) hypotension and metabolic acidosis developed in all ponies after correction of colonic torsion, cardiac index increased initially, but then decreased significantly (P < 0.05) over the study period. Mean times between correction of torsion and onset of cardiac failure and death were not different between groups. Significant (P < 0.05) thrombocytopenia developed during the reperfusion period in control ponies, but not in WEB-treated ponies. Blood leukocyte concentration in control ponies was more variable and significantly (P < 0.05) decreased immediately upon reperfusion, compared with that in WEB-treated ponies. We conclude that although the cardiovascular responses to colonic ischemia and reperfusion are not prevented by use of a specific PAF-antagonist, specific peripheral cellular responses are mediated by PAF. PMID- 8498752 TI - Effects of short-term cast immobilization on equine articular cartilage. AB - Hexosamine concentration (an index of proteoglycan content), DNA content (an index of cellularity), and [35S]sulfate incorporation (an index of proteoglycan synthesis) of articular cartilage were measured in biopsy specimens from medial proximal sesamoid bone, medial condyle of the third metacarpal bone, and proximal dorsal rim of the proximal phalanx in both metacarpophalangeal joints of 6 adult horses. One limb was then placed in a fiberglass cast that extended down from the proximal portion of the metacarpus and enclosed the hoof; the other limb was not casted. After 30 days of stall confinement, additional specimens were taken from the medial proximal sesamoid bone, medial condyle of the third metacarpal bone, midproximal portion of the proximal phalanx, distal portion of the proximal phalanx, and proximal portion of the middle phalanx of both limbs for comparison. Immobilization resulted in an apparent decrease in the hexosamine content of the cartilage when the 30-day immobilized vs 30-day mobilized specimens were analyzed. This decrease was accentuated by opposing trends in the 2 limbs. The immobilized cartilage tended to lose hexosamine, whereas the mobilized limb tended to gain hexosamine during the 30-day period; a similar trend also was seen with [35S] incorporation, but this trend was not statistically significant. The largest change was a significant increase in glycosaminoglycan synthesis in the mobilized limb, compared with little change in the immobilized joint cartilage. We concluded that contralateral limbs are unsuitable for controls in immobilization studies because of their biological response to increased weight bearing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498753 TI - Diagnosis of naturally acquired type-I and type-II diabetes mellitus in cats. AB - After IV administration of 0.5 mg of glucagon/cat, glucose tolerance and insulin secretory response were evaluated in 10 lean cats, 10 obese cats, and 30 cats with diabetes mellitus. Blood samples for glucose and insulin determinations were collected immediately before and at 5, 10, 15, 30, 45, and 60 minutes after IV administration of glucagon. Baseline serum insulin concentration and insulin secretory response were used to classify diabetes mellitus in the 30 cats as type I or type II. Mean (+/- SEM) baseline and 30-minute serum glucose concentrations in obese cats were significantly (P < 0.05) decreased, compared with values in lean cats, but were similar at all other blood sample collection times. Serum glucose concentration in diabetic cats was significantly (P < 0.05) greater than values in obese and lean cats at all blood sample collection times. Two statistically different insulin responses to IV administration of glucagon were seen in diabetic cats. Of the 30 diabetic cats, 23 had minimal insulin secretory response after glucagon administration (ie, serum insulin concentration was at or below sensitivity of the insulin assay). Seven diabetic cats had baseline serum insulin concentration similar to that of obese cats and significantly (P < 0.05) greater than that of lean cats and of the other 23 diabetic cats. In these 7 diabetic cats, serum insulin concentration increased after glucagon administration. Total insulin secretion was not significantly different between these 7 diabetic cats and the lean and obese cats, and was significantly (P < 0.05) greater than total insulin secretion in the other 23 diabetic cats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498754 TI - Transcutaneous oxygen monitoring for predicting skin viability in dogs. AB - Transcutaneous oxygen (PO2-TC) monitoring is commonly used in human medicine for evaluating skin viability. The application of transcutaneous monitoring for evaluating skin viability in dogs was investigated. The changes in PO2-TC values were measured from 16 avascular skin flaps created along the lateral hemithoraces of 4 dogs. Transcutaneous oxygen values were serially recorded from the vascular base and avascular apex of each flap for 12 hours after surgery. A single transcutaneous measurement was obtained from each flap base and apex 24 hours after surgery. Serial arterial blood gas analyses were obtained to compare central oxygen values with PO2-TC values. Full-thickness skin biopsy specimens were harvested from the base and apex of each flap 24 hours after surgery. The flaps were observed for 4 days and then excised for histologic examination. A subjective grading scale was used to assess histologic changes. Throughout the 12 hour period and at 24 hours, a statistically significant difference was found between the PO2-TC values for apices and bases of the flaps. The mean PO2-TC for all bases was 90.9 mm of Hg +/- 3.3 SEM, and the mean PO2-TC for all apices was 21.2 mm of Hg +/- 1.8 SEM. The mean regional perfusion index (apex PO2-TC/base PO2-TC) was 0.23 +/- 0.02. The subjective numbers assigned to the biopsy specimens were statistically evaluated by using a paired Student's t test and a Wilcoxon signed-rank test. A significant difference was found between the numbers for the collective bases and apices with both tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498755 TI - Evaluation of skin viability in dogs, using transcutaneous carbon dioxide and sensor current monitoring. AB - Transcutaneous oxygen monitoring is commonly used in human beings to assess skin viability. Little attention has been directed toward the use of transcutaneous carbon dioxide (PCO2-TC) monitoring for the same purpose. The application of PCO2 TC monitoring for evaluating skin viability in dogs was investigated. The changes in PCO2-TC and local power reference (LPR) values were measured from 16 skin flaps created along the lateral hemithoraces of 4 dogs. Transcutaneous PCO2 and LPR values were serially recorded from the base and apex of each flap for 12 hours. A single measurement was obtained from each flap base and apex 24 hours after surgery. Arterial blood gas analyses were obtained to compare central PCO2 values with peripheral skin PCO2 values. The flaps were observed for 4 days and then harvested for histologic examination. Full-thickness skin biopsy specimens were obtained 24 hours after surgery and when the flaps were harvested to evaluate the viability of the apex and base of the flaps. A subjective grade was assigned to all skin biopsy specimens during histologic examination. For all measurements, a significant difference was found between the PCO2-TC values for apices and bases of the flaps. The mean PCO2-TC for all bases was 52.66 mm of Hg +/- 2.24 (SEM), and the mean PCO2-TC for all apices was 106.4 mm of Hg +/- 2.44. The regional carbon dioxide index (apex PCO2-TC/base PCO2-TC) was 2.02. A significant difference was not found between the LPR values for bases and apices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498756 TI - Evaluation of the caudoventral portion of the mandible as a donor site for corticocancellous bone for periodontal surgery in dogs. AB - Corticocancellous bone graft was obtained from the caudoventral portion of the mandible of 8 dogs. The recipient site was an alveolar jugal and alveolar defect from vital root amputation of the mesiobuccal root of the maxillary fourth premolar. Anatomic observations of 20 canine cadavers indicated that guidelines for harvesting bone from the caudoventral portion of the mandible of dogs were the mesial aspect of the masseteric fossa, the distal aspect of the roots of the first mandibular molar, and the ventral aspect of the mandibular canal. The mean weight of corticocancellous bone harvested was 0.4 +/- 0.1 g. Harvested corticocancellous bone was adequate to fill recipient sites measuring a mean volume of 105.0 +/- 28.5 mm3. Histologic evaluation of the recipient site revealed progressive osseous integration of the bone-graft site during a mean follow-up period of 3.5 +/- 1.9 months. There was normal bone healing of the donor site without adverse effects on the mandibular molars or neurovascular structures of the mandibular canal. Vital amputation sites receiving silver amalgam had evidence of plasmacytic/lymphocytic inflammation associated with residual silver amalgam in the bone-graft area. The caudoventral portion of the mandible may be used as a donor site for autogenous corticocancellous bone in periodontal surgery of dogs. PMID- 8498757 TI - Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices. AB - OBJECTIVE: Comparison of the safety and efficacy of endoscopic sclerotherapy and ligation for the treatment of bleeding esophageal varices. DESIGN: Randomized, controlled trial. SETTING: An urban county hospital. PATIENTS: Patients with clinically severe bleeding from esophageal varices. INTERVENTION: A total of 77 patients were randomly assigned to receive sclerotherapy or ligation at the initial endoscopic examination. Treatment was repeated weekly until variceal obliteration was achieved. After eradication, patients had endoscopic examinations every 3 months or for any episode of rebleeding. Recurrent varices were treated with the originally assigned form of endoscopic therapy. MEASUREMENTS: Patients were assessed for further bleeding, for transfusion requirements, for time in hospital, for variceal eradication, for number of treatment sessions required, for complications, for treatment failure, and for risk of death. RESULTS: Rebleeding tended to be less frequent with ligation than with sclerotherapy: 10 of 38 (26%) compared with 17 of 39 (44%) (difference, 17% [95 CI, -4% to 38%]), but results in the two groups were comparable for blood transfusions, for length of hospital stay, and for risk of death. Comparison of Kaplan-Meier estimates of time to rebleeding and death showed no statistical differences between treatments. Complications were less common in the ligation group: fewer patients in the ligation group had esophageal strictures (0 of 38 compared with 13 of 39 [33%]; P < 0.001) and had complicated esophageal ulcers (1 of 38 [2.6%] compared with 6 of 39 [15%]; P = 0.11). In addition, fewer ligation treatments were required to achieve variceal eradication (4.1 +/- 0.3 compared with 6.2 +/- 0.4; P < 0.001). CONCLUSION: Endoscopic ligation causes statistically fewer local complications than sclerotherapy and achieves variceal eradication more rapidly. Ligation is a viable alternative to sclerotherapy and may have some advantages as a treatment for bleeding esophageal varices. PMID- 8498758 TI - Minocycline compared with doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis. AB - OBJECTIVE: To compare the efficacy and tolerability of minocycline versus doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis. DESIGN: Randomized, double-blind trial. SETTING: Sexually transmitted disease clinics. PATIENTS: 151 men and 102 women with nongonococcal urethritis, mucopurulent cervicitis or whose sexual partner had either condition or a positive culture for Chlamydia trachomatis. INTERVENTIONS: Minocycline, 100 mg nightly, or doxycycline, 100 mg twice daily, each administered for 7 days. MEASUREMENTS: At each visit (days 14 +/- 3, 28 +/- 5, and 49 +/- 7) patients were questioned regarding symptoms, signs, drug compliance, and sexual contact. Cultures for C. trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis were obtained at each visit. RESULTS: 253 patients were enrolled (133, doxycycline; 120, minocycline). Chlamydia trachomatis was initially isolated from 31% of men and 39% of women. Men with a positive smear had a higher symptom/sign score (P < 0.001) and were more likely to have chlamydia (P = 0.004). Positive endocervical smears were not associated with symptoms or signs (P > 0.2) but correlated with isolation of chlamydia (P < 0.001). One hundred sixty-two patients (64%) completed the study. The proportion with urethritis or cervicitis did not differ by treatment group at any follow-up visit (P > 0.08). Unprotected sexual contact did not affect clinical or microbiological cure rates. Adverse effects occurred more frequently in the doxycycline group (men: 43% versus 26%; P = 0.05; women: 62% versus 35%; P = 0.009). Although the proportion with dizziness did not differ by drug administered (P = 0.1), dizziness was reported more often by women (11% versus 3%). CONCLUSIONS: Minocycline, 100 mg nightly, was as effective as doxycycline, 100 mg twice daily, each given for 7 days in the treatment of nongonococcal urethritis and mucopurulent cervicitis. Vomiting and gastrointestinal upset occurred more frequently in the doxycycline group. PMID- 8498759 TI - Dose-response effects of methadone in the treatment of opioid dependence. AB - OBJECTIVE: To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: A methadone treatment research clinic. PATIENTS: Participants (n = 247) were opioid dependent patients with a high rate of cocaine use. INTERVENTION: All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day. Individual counseling and group therapy were included. MEASUREMENTS: Treatment retention and illicit drug use as determined by intensive urine monitoring. RESULTS: Retention was better for patients who remained on active medication. By treatment week 20, retention was 52.4% for the 50-mg, 41.5% for the 20-mg, and 21.0% for the 0-mg group (50 versus 0 and 20 versus 0, P < 0.05; 50 versus 20, P > 0.05). Only the 50-mg treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg and 0-mg groups, respectively; P < 0.05) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20- and 0-mg groups, respectively; P < 0.05). CONCLUSIONS: There is a dose-response effect for methadone treatment. Doses as low as 20 mg may improve retention but are inadequate for suppressing illicit drug use. PMID- 8498760 TI - Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group. AB - OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis. PMID- 8498761 TI - Reduction of lower extremity clinical abnormalities in patients with non-insulin dependent diabetes mellitus. A randomized, controlled trial. AB - OBJECTIVE: To evaluate the effect of a patient, health care provider, and systems intervention on the prevalence of risk factors for lower extremity amputation in patients with non-insulin-dependent diabetes. DESIGN: Blinded, randomized, controlled trial. SETTING: Academic general medicine practice. PARTICIPANTS: Of the 395 patients with non-insulin-dependent diabetes who underwent the initial patient assessment, 352 completed the study. INTERVENTION: The 12-month intervention was multifaceted. Patients received foot-care education and entered into a behavioral contract for desired self-foot care, which was reinforced through telephone and postcard reminders. Health care providers were given practice guidelines and informational flow sheets on foot-related risk factors for amputation in diabetic patients. In addition, the folders for intervention patients had special identifiers that prompted health care providers to: 1) ask that patients remove their footwear, 2) perform foot examinations, and 3) provide foot-care education. RESULTS: Patients receiving the intervention were less likely than control patients to have serious foot lesions (baseline prevalence, 2.9%; odds ratio, 0.41 [95% CI, 0.16 to 1.00]; P = 0.05) and other dermatologic abnormalities. Also, they were more likely to report appropriate self-foot-care behaviors, to have foot examinations during office visits (68% compared with 28%; P < 0.001), and to receive foot-care education from health care providers (42% compared with 18%; P < 0.001). Physicians assigned to intervention patients were more likely than physicians assigned to control patients to examine patients' feet for ulcers, pulses, and abnormal dermatologic conditions and to refer patients to the podiatry clinic (10.6% compared with 5.0%; P = 0.04). CONCLUSIONS: An intervention designed to reduce risk factors for lower extremity amputations positively affected patient self-foot-care behavior as well as the foot care given by health care providers and reduced the prevalence of lower extremity clinical disease in patients with diabetes. PMID- 8498762 TI - Transient systolic dysfunction after relief of cardiac tamponade. PMID- 8498763 TI - Hypothyroidism and primary pulmonary hypertension: an autoimmune pathogenetic link? PMID- 8498764 TI - The teaching and practice of cardiac auscultation during internal medicine and cardiology training. A nationwide survey. AB - OBJECTIVES: To assess the time and importance given to cardiac auscultation during internal medicine and cardiology training and to evaluate the auscultatory proficiency of medical students and physicians-in-training. STUDY DESIGN: A nationwide survey of internal medicine and cardiology program directors and a multicenter cross-sectional assessment of students' and housestaff's auscultatory proficiency. SETTING: All accredited U.S. internal medicine and cardiology programs and nine university-affiliated internal medicine and cardiology programs. PARTICIPANTS: Four hundred ninety-eight (75.6%) of all 659 directors surveyed; 203 physicians-in-training and 49 third-year medical students. INTERVENTIONS: Directors completed a 23-item questionnaire, and students and trainees were tested on 12 prerecorded cardiac events. MAIN OUTCOME MEASURES: The teaching and proficiency of cardiac auscultation at all levels of training. RESULTS: Directors attributed great importance to cardiac auscultation and thought that more time should be spent teaching it. However, only 27.1% of internal medicine and 37.1% of cardiology programs offered any structured teaching of auscultation (P = 0.02). Programs without teaching were more likely to be large, university affiliated, and located in the northeast. The trainees' accuracy ranged from 0 to 56.2% for cardiology fellows (median, 21.9%) and from 2% to 36.8% for medical residents (median, 19.3%). Residents improved little with year of training and were never better than third-year medical students. CONCLUSIONS: A low emphasis on cardiac auscultation appears to have affected the proficiency of medical trainees. Our study raises concern about the future of this time-honored art and, possibly, other bedside diagnostic skills. PMID- 8498765 TI - Genetic relatedness of lymphoid malignancies. Transformation of chronic lymphocytic leukemia as a model. AB - OBJECTIVE: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer. DATA SOURCES: An English-language medical literature search was done using MEDLINE (1982 to 1992) and CANCERLIT (1982 to 1992). An extensive manual search of the literature that included meeting abstracts and reports was also done. Approximately 500 articles, abstracts, and book chapters were identified; 102 were selected for detailed analysis. DATA ANALYSIS: Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities. CONCLUSIONS: In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event. PMID- 8498766 TI - Reasons for increasing administrative costs in hospitals. AB - OBJECTIVE: To evaluate trends in administrative expenditures by examining changes in administrative costs compared with other areas of the hospital budget, changes in expenditures for patient care departments compared with nonpatient care departments, and departments with a greater number of regulatory requirements compared with those with fewer regulatory requirements. DESIGN: Annual hospital operating budgets submitted to Blue Cross were examined for an 8-year period from 1983 to 1990. PARTICIPANTS: Seventy hospitals in Western Pennsylvania. MEASUREMENTS: Annual operating expenditures. RESULTS: Total administrative expenditures showed a larger growth rate (90%) than service departments (29%), ancillary services (30%), professional care (52%), miscellaneous expenses (70%), and the total hospital budget (45%). Administrative costs increased from 10.6% as a proportion of the total hospital budget in 1983 to 13.9% in 1990. These increases were seen regardless of hospital size. Departments with a greater number of regulatory obligations had a greater increase in expenditures (84%) than did departments with fewer regulatory requirements (5%). However, overall expenditures in departments with direct patient care responsibilities did not increase appreciably faster (44%) than in departments not providing clinical services (46%), possibly reflecting the fact that administrative costs may be increasing equally in both areas. CONCLUSIONS: Administrative costs were found to be one of the fastest growing components of hospital budgets. Future research should determine the effect of these increases on the quality of patient care. PMID- 8498767 TI - Changing patterns of medical practice: protein restriction for chronic renal failure. AB - The use of dietary protein restriction for renal failure has fluctuated during the past 125 years. These fluctuations reflect not only the state of medical knowledge but also social, economic, and cultural factors. Factors inhibiting use of dietary treatment have been its status as an aspect of hygiene rather than as active therapy; the opinions of dominant practitioners and scientists around midcentury, including a presumption that renal adaptation to a high-protein diet must be appropriate; fear of malnutrition and a cultural belief in the virtue of dietary protein; unwillingness by physicians and patients to restrict consumption or lifestyle; and professional identification with the technologies of dialysis and renal transplantation. Factors promoting dietary treatment have been rediscovery of previous work on protein-induced renal injury; a sense that homeostatic compensations could have adverse consequences; federal incentives to curb consumption of scarce resources such as renal dialysis; and the integration of research on, and therapeutic use of diet into scientific medicine. A large ongoing study of dietary protein restriction to limit renal injury will add to our knowledge of this treatment; its application will surely be informed by social and cultural considerations. PMID- 8498768 TI - Transfusion history and cancer risk in older women. AB - OBJECTIVE: To test the hypothesis that history of blood transfusion is associated with an increased incidence of cancer in older women. DESIGN: Prospective cohort study. SETTING: General community in the state of Iowa. PARTICIPANTS: Random sample of 37,337 cancer-free Iowa women ages 55 to 69 years. MEASUREMENTS: Transfusion history was assessed with a mailed questionnaire completed in January 1986. Cancer incidence in 5 years was ascertained by a population-based cancer registry. RESULTS: Women who had ever received a blood transfusion were at an increased risk for non-Hodgkin lymphoma (relative risk (RR) = 2.20; 95% CI, 1.35 to 3.58) and kidney cancer (RR = 2.53; CI, 1.34 to 4.78). The relative risks for these cancers were greater with decreasing time from first transfusion. No increased risk occurred for cancers of the breast, lung, uterine corpus, ovary, pancreas, colon, rectum, skin (melanoma), or for all cancers considered together. CONCLUSION: These findings suggest that previous blood transfusion may be a risk factor for non-Hodgkin lymphoma and kidney cancer but is not associated with the most common neoplasms. PMID- 8498769 TI - Tribute. PMID- 8498770 TI - Endoscopic ligation of esophageal varices. PMID- 8498771 TI - Superantigens and microbial pathogenesis. PMID- 8498772 TI - Diagnosing sinusitis. PMID- 8498773 TI - Modulation of diabetes mellitus in AIDS. PMID- 8498774 TI - Accrediting correctional health care. PMID- 8498775 TI - Survey of residents about their programs. PMID- 8498776 TI - Reporting clinical trial results. PMID- 8498777 TI - Training generalists to do procedures. PMID- 8498778 TI - Physician disclosure of financial incentives. PMID- 8498779 TI - [Barrett's esophagus: current attitude]. PMID- 8498780 TI - [Cancer of the gallbladder. Epidemiology, diagnosis and prognostic factors]. AB - Between 1978 and 1986, 77 cases of primary gallbladder carcinoma were recorded in the Calvados Digestive tumors Registry (covering a population of 589,559 inhabitants) among 125 extra-hepatic bile duct carcinomas. The crude incidence was 2.4/100,000 in females and 0.6 in males (sex-ratio = 3.8). Cholelithiasis was demonstrated in 81.3%. Gallbladder carcinoma was diagnosed correctly preoperatively in only 13.5%. Out of the 74 operated patients, there were only 6 mucosal or sub-mucosal carcinomas and liver involvement was present in 40%. Diagnosis was made post-operatively on the resected specimen in 13 patients (non reoperated) Operative mortality was 24%. The overall survival was 14.7% at one year, 4% at 5 years (median = 3 months). In multivariate analysis the prognostic factors were: curative resection (9 patients, 3-year survival: 55%), parietal extension, liver involvement. No significant trend in prognosis could be demonstrated during the study period. PMID- 8498781 TI - [Value and limitation of ultrasound-guided percutaneous drainage in acute lithiasic cholecystitis]. AB - The aim of this study was to evaluate the results of ultrasound guided percutaneous cholecystostomy in the treatment of acute calculous cholecystitis. From July 1987 to December 1980, 32 patients (mean age = 80) were treated prospectively by this procedure. There was only one death (3%). Successful treatment was achieved in 70% of the patients and was related with mobilization of the gallstone impacted in the infundibulum of the gallbladder. When mobilization of the impacted stone cannot be obtained, surgery is indicated within one week, as later surgery is much more difficult. Twenty-three percent of the patients successfully cured later died from non biliary disease; this indicates the very poor condition of most of the patients. In our experience, percutaneous cholecystostomy is a safe and minimally invasive procedure in the treatment of elderly high-risk patients presenting with acute calculous cholecystitis. PMID- 8498782 TI - [Fractures of the navicular bone. Apropos of 48 cases]. AB - Fracture of the navicular bone is rare and sometimes difficult to diagnose. Surgical treatment with direct osteosynthesis gives good results except in the case of fractures of the tubercles. In view of the poor postoperative course of fracture-dislocations, immediate talo-navicular-cuneiform arthrodesis may be proposed. PMID- 8498783 TI - [Mini-invasive surgery. Towards the surgery of the year 2000]. PMID- 8498784 TI - What's new in thoracic surgery? PMID- 8498785 TI - [Isolated portal vein thrombosis: a rare complication of chronic pancreatitis]. AB - In chronic pancreatitis (CP) portal vein thrombosis (PT) is a less well known complication than splenic vein thrombosis (ST). In the literature up until 1990, 26 cases with PT, have been reported and only 10 cases presented a isolated PT, without ST. We report a new case of isolated PT without ST in a non alcoholic man, who presented with gastroesophageal CP and a cavernomatous transformation of the portal vein. No varices ere detected by endoscopy; because the risk of bleeding was very small, a prophylactic treatment was unnecessary. The pancreas was resected preserving the spleen and cavernomatous transformation or the periportal veins and the patient was cured from his pains. The surgical tactic is an original treatment, particularly when curable pancreatic cancer is suspected. PMID- 8498786 TI - [Surgical treatment of multivisceral intra-abdominal recurrences and metastases]. AB - From 1988 to 1990, 467 patients were operated a total of 850 times for malignant intra-abdominal tumours. Analysis of these 850 operations revealed that 205 were performed for recurrences with or without metastasis and 59 were performed for metastasis. The operations for recurrences were elective in 158 cases and consisted of 86 local radical procedures and 72 non-radical procedures. 47 operations for recurrences were performed as emergency procedures and were non radical in 45 cases. With 55 of 59 operations for metastasis the majority of these operations was performed electively and locally radical. The majority for metastases were performed electively and were locally radical. The majority of life-threatening emergency situations were controlled (129 of 141 operations, 92%) and two-thirds of these patients left hospital with a satisfactory quality of life (Karnofsky index > 50 in 83 of the 141 operations). Consequently, repeated operations and the combination of surgery with adjuvant therapy can control malignant disease for several years with a satisfactory quality of life. PMID- 8498787 TI - [Intra-epithelial cancer of the cervix uteri. Epidemiological and therapeutic evolution. Apropos of 207 cases]. AB - Through a retrospective study of 207 CIN III of the cervix uteri, with a medial follow-up of 6 years, the authors are showing the evolution in the management of that pathology. Different reasons are invoked: 1) the practice of systematic Papanicolaou smears reveals dysplasia of the cervix in younger women, justifying treatments that preserve obstetrical future; 2) the histological classification is now well established, the old terminologies is being replaced by the international term of CIN III. 3) the colposcopy can localize the transformation zone, allowing more conservative treatments. The treatment of reference was initially hysterectomy and is now conization for non-menopausal women; but this conservative evolution is not yet finished. PMID- 8498788 TI - [Para-hiatal gastric strangulation after Toupet's operation]. AB - An exceptional case of incarcerated para-hiatal hernia with gastric necrosis, developing 7 years a Toupet procedure, is reported. To our knowledge, this is the first reported case of this complication after a surgical anti-reflux procedure without diaphragmatic counter incision. The mechanism, diagnostic difficulties and treatment are discussed. PMID- 8498790 TI - [Surgical videotapes: content and style]. PMID- 8498789 TI - [Intestinal perforation by a fish bone. Apropos of a case and review of the literature]. AB - We report a case of transverse colon perforation by a fish bone (Grouper) in a toothless-old female. A review of the literature revealed a great variety of foreign bodies which may cause perforations at variable sites of the gastrointestinal tract. Fish bones were responsible for 46% of intestinal perforations in a review of 24 cases collected in 1984. Advanced age and poor patient dentition, as well as mental debility constitute predisposing factors for the swallowing of foreign bodies. Emergency radiology may be required. An exaggerated inflammatory reaction may give rise to a misleading pseudo tumor appearance. We agree that a well conducted and well analysed clinical history associated with a careful pathologic examination are very helpful in the diagnosis. PMID- 8498791 TI - [Traumatic bilateral testicular dislocation]. AB - The authors report one case of bilateral traumatic dislocation of the testes. A rapid analysis of literature enable to emphasize the usual mechanism (motorcycle accident), different anatomic types and therapeutic behaviour; immediate closed reduction and more often, surgical orchidopexy. PMID- 8498792 TI - [Protection of invention "in the medical field"]. PMID- 8498793 TI - [Imaging of the future in celiosurgery]. PMID- 8498794 TI - [Positioning of the patient for esophageal hiatus surgery]. AB - A prospective study was conducted to determine the best position of patients undergoing esophageal hiatus surgery. Three positions were compared: 1) use of a cushion; 2) use of the operating table block, and 3) the ordinary supine position. Twenty-four consecutive patients undergoing surgical approach to the esophageal hiatus were placed successively in the three positions. The distance between the xiphoid process and the hiatus area was shorter in positions 1 and 2 by an average of 0.8 cm as compared with position 3 (p < 0.001). The angle determined by the xiphoid process and a horizontal line passing through the hiatas area was 14 degrees and 8 degrees, more when the cushion and the block were used, respectively, as compared with the supine position (p < 0.01). We recommend the use of the cushion in hiatal surgery, affording better exposure and therefore a more comfortable approach to the hiatal area as compared with the supine position. PMID- 8498795 TI - [The school of surgery in Lyon. Past--present--future]. PMID- 8498796 TI - [Markers of hemostasis and myocardial infarction in persons under 40 years of age]. AB - Coronary disease before the age of 40 has special clinical and pathogenic features. The authors sought evidence of the existence of abnormalities of hemostasis markers in 39 patients aged under 40, several weeks after a myocardial infarction (MI). Blood samples were drawn a mean of 8 months after the MI. These laboratory studies included assay of C and S proteins, fibrinogen, clotting factors VII and VIII and antithrombin III, as well as detection of any possible circulating anticoagulant. Plasma levels of platelet factor 4 (PT4) and of beta thromboglobulin (BTG) were measured in the same sample, enabling determination of the BTG/PF4 ratio. Only fibrinogen and plasma levels of platelet proteins were abnormal, revealing a significant difference between patients with multi-vessel disease and those with single vessel disease or free of severe angiographic lesions. Platelet activation appeared to persist some time after the MI, chiefly in patients with multi-vessel disease, and showing no relation to either age or treatment. Conclusions require prudence in view of difficulties in interpreting plasma assays of PF4 and of BTG. PMID- 8498797 TI - [Angioplasty of the subclavian arteries. Immediate and mid-term results]. AB - The authors report the immediate and mid-term results of a retrospective study concerning 30 attempted angioplasties in 30 patients with tight stenosis of the subclavian artery. The cohort consisted of 23 men with a mean age of 57.5 and 7 women with a mean age of 57.7. Twenty three patients had symptoms and 7 were asymptomatic. There were 2 technical failures related to impossibility of passage through the stenosis. There were two complications during the immediate postoperative period in the form of obstruction at the arterial puncture site with no long term functional consequences. Clinical evaluation after a mean follow-up of 32.5 months showed that 25 (89.2%) of 28 patients with a good primary result were improved from a clinical and/or blood pressure after a mean follow-up of 34.5 months in 19 (82.6%) of the 23 patients undergoing this investigation. This study confirms the satisfactory efficacy of subclavian angioplasty with a low complication rate. It would seem legitimate to suggest angioplasty as first line treatment of stenosis of the subclavian artery and to reserve surgery for failures or contraindications to the technique. PMID- 8498798 TI - [Systematic cardiovascular evaluation and hypercholesterolemia. Results in 200 asymptomatic patients]. AB - This study reports the results of routine evaluation to detect coronary and carotid atherosclerosis in 200 asymptomatic and hypercholesterolemic patients (48 +/- 10 years: 72.5% men). All patients underwent physical examination, blood lipid profile, an exercise test and cervical echo-doppler. If the exercise electrocardiogram was abnormal, a thallium isotope scan and/or coronary arteriography were performed. Hypercholesterolemia was severe (3.03 +/- 0.52 g/l). 77.5% of patients had pure hypercholesterolemia. Carotid atherosclerosis in the form of plaque (27.5%) or stenosis (3.5%) was found in 31% of patients. This carotid atheroma was commoner in older patients (51.9 +/- 9 years as against 47 +/- 10 years, p < 0.01). Twenty patients (10%) had electrical signs of ischemia provoked by exercise. Six of them had a normal thallium isotope scan and did not undergo coronary arteriography. Coronary arteriography was abnormal in 10 patients (5%): 7 had stenotic lesions and 3 showed evidence of spasm during the methylergometrine test. In total, the hypercholesterolemic patients investigated here were characterised by subclinical atherosclerosis which was frequent but certainly underestimated by non-invasive studies. The existence of an atherosclerotic lesion is an additional argument in favour of starting cholesterol-lowering treatment. PMID- 8498799 TI - [Vasculitis complicating treatment with streptokinase: delayed allergic reaction]. AB - The authors report a case of vascular purpura occurring eleven days after the injection of streptokinase for a myocardial infarction. This adverse event falls within a context of hypersensitivity vasculitis (type III). In this particular case, imputation to the thrombolytic agent was established by the official method for the imputation of adverse or toxic effects of drugs. Routine renal function studies were normal. The outcome was satisfactory following rest only but the existence of a mixed cryoglobulinemia, responsible secondarily for cold-related distal ischemic symptomatology of the lower limbs led to the successful prescription of a short course of corticosteroids. PMID- 8498800 TI - [Isolated pericardial metastasis of digestive cancer disclosed by tamponade]. AB - The authors report a case of a single secondary tumour of the pericardium presenting as tamponade and occurring three years after sigmoidectomy for an adenocarcinoma of the colon. Gastrointestinal investigations confirmed the absence of any local tumour recurrence. The originality of this case lies in the presentation and isolated nature of this metastasis. Attempted surgical excision failed which, in view of the patient's good general condition, led to suggestion of FUFOL type chemotherapy. PMID- 8498801 TI - [A new case of false aneurysm of the superior mesenteric artery]. AB - We report a case of successful management of a false aneurysm of the superior mesenteric artery. The only helpful clinical manifestations were episodes of previous abdominal pain and a history of bacterial endocarditis. The surgical management involved endo-aneurysmorrhaphy. The patient's post-operative course was unremarkable. PMID- 8498802 TI - [Dilated cardiomyopathy in acromegaly worsening under octreotide treatment. Apropos of a case]. AB - Dilated cardiomyopathy associated with acromegaly is rare, but may improve with octreotide, a somatostatin analogue. The authors give the first description here of paradoxical worsening in cardiac function during such treatment, with the onset of episodes of acute decompensation following each attempt at starting treatment. Thus worsening was confirmed objectively by a challenge test with octreotide: increased dyspnea, fall in shortening fraction and in echocardiographic cardiac output (of 17 to 14% and 4 to 3 l/min respectively), a decrease in isotopic ejection fraction from 15 to 6% and this in parallel with efficacy regarding hormone levels of GH and IGF1 and a reduction in tumour size by CT scan. No further episode of decompensation occurred after treatment was stopped permanently. The patient underwent a transplant 3 months later. Suppression of the positive inotropic effect of GH by octreotide, associated with an increase in peripheral resistance is suggested. A negative inotropic effect of this hormonal analogue on too advanced a case of heart disease is also a possibility. PMID- 8498803 TI - [Dilated cardiomyopathy disclosing dermatopolymyositis. Management]. AB - Cardiac involvement in dermatopolymyositis is common but rarely symptomatic. Cardiac failure as the presentation is very rare. No correlation exists between the severity of muscular involvement and cardiac involvement. Myocarditis is not uncommon and must be borne in mind if CK MB are above 3% of total CK. It is always associated with electrocardiographic abnormalities. Corticosteroids remain first line treatment. They generally lead to regression of cardiac problems which are usually of secondary importance. If cardiac involvement is severe, the spectacular action of venoglobulins should lead to their use being envisaged from the outset, combined with corticosteroids. PMID- 8498804 TI - [Thrombolysis and acute venous thromboembolic disease]. AB - Thrombolytic agents are widely used as first line treatment in severe acute pulmonary embolisms. While their indications are well defined, no controlled trial exists to provide definite evidence of their ultimate effectiveness in terms of mortality. Nevertheless, therapeutic advances and the good results obtained in terms of satisfactory changes in hemodynamic and angiographic parameters have led to renewed evaluation at the present time of the ways in which they are used in thrombo-embolic disease: administration of thrombolytics as repeated boluses in order to decrease the risk of hemorrhagic complications; and extension of the indications of thrombolysis to the venous component of thrombo-embolic disease. PMID- 8498805 TI - [Effects of urapidil by intravenous injection on pulmonary circulation and cardiac function in left ventricular failure]. AB - The hemodynamic effects of urapidil were studied in 10 patients with secondary pulmonary hypertension investigated for the purpose of possible inclusion on a heart transplant waiting list. All patients gave their consent to participate. Nine patients had a dilated cardiomyopathy and 1 three-vessel coronary disease with diffuse hypokinesia. All were treated with digitalis, diuretics, converting enzyme inhibitors or calcium antagonists. Hemodynamic effects were measured 5 and 25 minutes after the slow intravenous injection of 50 mg of urapidil. Urapidil caused a significant decrease in pulmonary pressures (-20%) and total pulmonary resistance (-42.5%). The fall in systemic arterial resistance was of the same degree (41.5%). The fall in pulmonary arterial resistance was also significant ( 26%). The increase in cardiac output was +35%, with no change in left ventricular myocardial function indices. Thus, in patients with congestive left ventricular failure and secondary pulmonary hypertension already treated with vasodilators, urapidil resulted in a hemodynamic improvement after intravenous administration, demonstrating a synergistic action with that of other vasodilators. This synergistic action could be used to test pulmonary arteriolar vasodilatation reserves during the hemodynamic assessment of patients in whom a heart transplant is contemplated. PMID- 8498806 TI - Multifocal motor neuropathy: response to human immune globulin. AB - Multifocal motor neuropathy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis. Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immune globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distal, limb weakness for 5 to 18 years. Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serum titers of anti-GM1 IgM antibody. All patients were treated with HIG, 1.6 to 2.4 gm/kg, given intravenously over 3 to 5 days. Strength improved in all patients 3 to 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement varied from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 of 8 patients. The serum anti-GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conclude that HIG may be an effective therapy for patients with MMN. PMID- 8498807 TI - Campylobacter jejuni strains from patients with Guillain-Barre syndrome belong mostly to Penner serogroup 19 and contain beta-N-acetylglucosamine residues. AB - Campylobacter jejuni was isolated from stool cultures from 14 (30%) of 46 patients with Guillain-Barre syndrome and from 6 (1.2%) of 503 healthy persons, and the difference was highly significant (p < 0.0001). In addition, serological evidence of recent C. jejuni infection was found in 5 of 29 patients with negative stool cultures. Therefore, 41% of patients were associated with C. jejuni infection. Ten of 12 (83%) isolates from patients with Guillain-Barre syndrome belonged to Penner serogroup 19, which is a rare serogroup in sporadic patients with C. jejuni enteritis. In the lectin typing study, all serogroup 19 strains from patients with Guillain-Barre syndrome were shown to contain terminal beta-N-acetylglucosamine residues on their cell surface, but serogroup 19 strains from patients with enteritis were not. PMID- 8498808 TI - Retinal ganglion cells in Alzheimer's disease and aging. AB - Optic nerve and retinal ganglion cell (GC) degeneration are possible explanations for the poor visual function reported in patients with Alzheimer's disease (AD). We investigated whether GC loss could be attributed to AD compared with control subjects by measuring the spatial density of GC (cells/mm2) with methods previously used to analyze the GC distribution of young normal retinas. Retinas from 4 autopsy-confirmed, severely demented patients with AD and 4 age- and sex matched control subjects (ages, 66-86 yr for both groups) without history of dementing or ocular disease were prepared as unstained whole mounts. There was no evidence for loss of GC within the central 43 degrees of vision in patients with AD. The density of GC subserving the central 11 degrees of vision was reduced by one-fourth in both AD and control eyes compared with retinas from young adults, as was GC density in a wedge of nasal retina. This loss may contribute to deficits in visual function found in aged individuals, whether or not they have dementia. PMID- 8498809 TI - Risk factors for late-onset Alzheimer's disease: a population-based, case-control study. AB - Our current knowledge of risk factors for Alzheimer's disease is limited and primarily addresses early-onset disease. This study aimed to determine the risk factors for late-onset Alzheimer's disease using a case-control approach. Ninety eight cases and 216 controls were gathered from an ongoing population survey on aging and dementia in Stockholm (the Kungsholmen Project). We found a high relative risk (3.2; 95% confidence interval, 1.8-5.7) with the presence of at least one first-degree relative affected by dementia. Among all the other risk factors, alcohol abuse (relative risk, 4.4; 95% confidence interval, 1.4-13.8) and manual work (relative risk for men of 5.3; 95% confidence interval, 1.1-25.5) emerged as positively associated. No clear association was found with a family history of Parkinson disease, advanced parental age at index delivery, season of birth, or previous head trauma. In conclusion, our data suggest that the main risk factor for late-onset Alzheimer's disease is a family history of dementia, as has been previously reported for early-onset disease. Moreover, alcohol abuse and occupational exposure might play a specific role for this form of the disease. PMID- 8498810 TI - Relationships between extrapyramidal signs and cognitive function in a community dwelling cohort of patients with Parkinson's disease and normal elderly individuals. AB - The relationship between extrapyramidal sign (EPS) severity and cognitive function was investigated in 184 patients with idiopathic Parkinson's disease (PD) and 301 normal elderly individuals from a community-dwelling cohort in northern Manhattan, New York City. Fifty-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of memory, orientation, abstract reasoning, language, construction, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD patients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but without overt idiopathic PD, showed widespread cognitive changes, including impairment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia. PMID- 8498811 TI - A population-based study of multiple sclerosis in twins: update. AB - This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors. PMID- 8498812 TI - Epileptic seizures after subarachnoid hemorrhage. AB - We studied predictive factors for the occurrence of epilepsy in 381 consecutive patients admitted within 72 hours after they had a subarachnoid hemorrhage from a ruptured intracranial aneurysm. Fits occurring in the presence of hyponatremia or within 12 hours after the initial bleed, rebleeding, or aneurysm surgery were classified as associated with these acute events and we did not regard these fits subsequent epileptic seizures. Thirty-five patients (9%) had one or more epileptic seizures, 12 hours to 1,761 days after the initial bleed (median value, 18 days). The following variables were included in the analysis: sex, age, history of hypertension, history of cardiovascular disease, loss of consciousness at ictus, sum score on the Glasgow Coma Scale on admission, sum score for the amount of cisternal blood and presence of intraventricular blood based on the initial computed tomography (CT) scan, occurrence of ictal seizures (seizures occurring within 12 hours after the onset), acute hydrocephalus, rebleeding, delayed cerebral ischemia, fluid intake, treatment with tranexamic acid, ventricular drainage, and aneurysm surgery. After multivariate analysis by means of Cox proportional hazards model with stepwise forward selection of the variables, a high cisternal blood score and rebleeding proved to be significantly related to epilepsy (hazard ratio = 2.06, p = 0.040; and hazard ratio = 3.02, p = 0.016), even after the exclusion of 28 patients who received perioperative prophylactic anticonvulsant therapy (hazard ratio = 2.31, p = 0.022; and hazard ratio = 3.65, p = 0.006, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498813 TI - Ocular torsion and tilt of subjective visual vertical are sensitive brainstem signs. AB - Deviations of the position of the eye in the roll plane, ocular torsion (OT), and the subjective visual vertical (SVV) were systematically studied in 111 patients with acute vascular brainstem lesions. Of the 111 patients, 104 (94%) showed a direction-specific pathological tilt of the static SVV in our series. Seventy-one (83%) of 86 patients exhibited pathological static OT of one (47%) or both (36%) eyes. OT and SVV tilts are therefore sensitive signs in acute unilateral brainstem disorders. Measurements of SVV and OT may prove to be useful components of the neuro-ophthalmological evaluation. With respect to the directions of pathological tilt, SVV and OT are generally in the same direction. Based on neuroimaging, we conclude that all unilateral brainstem lesions caudal to the upper pons cause ipsiversive OT of one or both eyes, with concurrent ipsiversive tilts of SVV adjustments; all lesions rostral to this pontine level cause contraversive tilts of OT and SVV. Evidence is presented that pathological tilts of OT and SVV are secondary to a dysfunction of the tonic bilateral vestibular inputs that stabilize the eyes and head in normal upright position in the roll plane and dominate our perception of verticality. PMID- 8498814 TI - Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/magnetic resonance scan. AB - Cerebral lymphoma is usually identified on computed tomographic/magnetic resonance scan as a homogeneously contrast-enhancing periventricular mass lesion. We present 10 patients with cerebral lymphoma who had nonenhancing tumor on computed tomographic (2 patients) or magnetic resonance scan (8 patients) either at the time of diagnosis or recurrence. The absence of enhancement caused diagnostic delay in all patients and suggests that tumor resides behind an intact blood-brain barrier, raising important therapeutic implications in the design of chemotherapeutic regimens. PMID- 8498815 TI - Dopamine agonist treatment of antegrade amnesia from a mediobasal forebrain injury. AB - We studied the persistent antegrade memory impairment in a woman whose brain had been surgically impaled, leaving a 1-cm-wide mediobasal tract of encephalomalacia that extended just anterior to the septal nuclei and medial to the nucleus accumbens. In a blinded, controlled, alternating repeated-measures protocol, bromocriptine significantly improved her verbal learning, functional memory, and daily recall, perhaps by acting on neurons that had been disconnected from the ventral tegmental tract's dopaminergic inputs. PMID- 8498816 TI - Progress and promise 1992: a status report on the NINDS. Implementation plan for the decade of the brain. PMID- 8498817 TI - Molecular genetics in neurology. PMID- 8498818 TI - Human immunodeficiency virus type 1 infection of the nervous system: pathogenetic mechanisms. AB - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with characteristic virological, clinical, and neuropathological findings in adults and children. Productive infection in the brain and spinal cord occurs in blood-derived macrophages, resident microglia, and multinucleated giant cells. Previous work implicated indirect mechanisms for neurotoxicity by HIV-1 gene products or by factors secreted from HIV-1--infected macrophages. However, this cannot explain the paradox between the small numbers of infected cells and the widespread tissue pathology. Based on recent studies from our laboratories, we suggest that HIV-1--infected macrophages can initiate neurotoxicity, which is then amplified through cell-to-cell interactions with astrocytes. Macrophage-astrocyte interactions produce cytokines tumor necrosis factor-alpha and interleukin-1 beta and arachidonic metabolites that cause astroglial proliferation and neuronal injury. Inevitably, the astrogliosis serves to amplify these cellular processes while brain infection maintains itself in macrophage and microglia and possibly in astrocytes (by restricted infection). These findings, taken together, provide fresh insights into how low numbers of productively infected cells could elicit progressive and devastating neurological impairment during HIV-1 disease, and suggest therapeutic strategies to interrupt the pathological process. PMID- 8498819 TI - The molecular biology of brain ischemia: trendy genes in sick neurons. PMID- 8498820 TI - Tremors are additive. PMID- 8498821 TI - Can neurologists survive or thrive with health care reform? AB - The economics of present-day health care and the politics of recent elections will forever change the practice of neurology. Managed care, outcomes research, limits on price and volume of services, diagnostic and treatment restraint, divestiture of ownership in health facilities, malpractice reform, increased use of preventive services, and administrative simplifications will all be part of the new practice of medicine, and hence neurology. The challenge for neurologists will be to define cost-effective neurological services, put greater emphasis on the most prevalent and costly diseases of the nervous system, and convince primary care providers and patients of their value. Health care reform is an opportunity and challenge for neurologists to improve patient access while achieving acceptable financing mechanisms. PMID- 8498822 TI - Dementia in Parkinson's disease: biochemical evidence for cortical involvement using the immunodetection of abnormal Tau proteins. AB - In order to elucidate the neurochemical basis of the dementia of Parkinson's disease, we compared samples of cerebral cortex from 24 nondemented parkinsonian patients and parkinsonian patients with various degrees of dementia, with those from patients with Alzheimer's disease and control subjects, using a quantitative Western blot analysis. An anti-paired helical filaments antibody was used for the immunodetection of the abnormally phosphorylated Tau proteins 55, 64, and 69, which are known to be specific and reliable biochemical markers of Alzheimer-type neurofibrillary degeneration. The frequency and intensity of immunodetection of the abnormal Tau triplet were higher in the demented parkinsonian subgroups than in the nondemented parkinsonian subgroup in the prefrontal area, temporal cortex, and entorhinal cortex but not in either the occipital or the cingular cortex. A quantification of abnormal Tau triplet by densitometry showed that unlike the results obtained in Alzheimer patients, the intensity of lesions in the cerebral cortex of the most demented parkinsonian patients was more severe in the prefrontal area versus the temporal area. This study (1) gives biochemical evidence for Alzheimer-type changes in the cortex of demented parkinsonian patients and (2) suggests that lesions of the prefrontal cortex may significantly contribute to the occurrence of cognitive changes at least in some patients with Parkinson's disease. PMID- 8498823 TI - The clinical and topographic spectrum of cerebellar infarcts: a clinical-magnetic resonance imaging correlation study. AB - We studied 34 consecutive patients with non-mass-producing cerebellar infarcts using a standard protocol of investigations including magnetic resonance imaging (MRI). We analyzed the topography of infarcts to determine the involved arterial territories and we correlated the findings with neurological dysfunction and potential causes of stroke. Sixteen patients had an infarct in the territory of the posterior inferior cerebellar artery (PICA); 2, in the territory of the anterior inferior cerebellar artery (AICA); 13, in the territory of the superior cerebellar artery (SCA); and 8 had junctional infarcts between the territories of the medial and lateral branches of the PICA or PICA/SCA territories. PICA or medial PICA territory infarcts were manifested by acute vertigo and truncal ataxia, while the patients with lateral PICA territory infarcts presented with unsteadiness, limb ataxia and dysmetria without dysarthria. Patients with infarcts in the AICA territory were characterized by limb and trunk ataxia associated with signs of lateropontine involvement. Patients with SCA territory infarcts presented with dysarthria, unsteadiness and/or vertigo, limb ataxia, and dysmetria. Cardiac embolism was the main cause of large infarcts in the territories of the PICA (8/16) or SCA (4/7). Multiple small infarcts were associated with vertebrobasilar atherosclerosis (8/12). These clinical-MRI correlations allow better definition of the topographic and etiological spectrum of cerebellar infarction, which was previously based on pathological studies in subjects with severe infarction. PMID- 8498824 TI - Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor. AB - The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor. PMID- 8498825 TI - Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions. AB - It is now well established that clinically stable patients with relapsing remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] < 3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients. PMID- 8498826 TI - Defecatory function in Parkinson's disease: response to apomorphine. AB - We evaluated the effects of the dopaminergic agent apomorphine on defecation and anorectal function in patients with Parkinson's disease (PD). A gastrointestinal symptom survey, extrapyramidal assessment, defecating proctogram, and anorectal manometric study were performed in 8 subjects with PD. Basal studies showing abnormalities were repeated following apomorphine administration. Prior defecographic abnormalities were normalized following apomorphine injection in 1 of 3 subjects and significant improvements in manometric parameters were observed in all 5 subjects who underwent repeat anorectal manometry. We conclude that apomorphine can correct anorectal dysfunction in PD, and that these abnormalities may be a consequence of dopamine deficiency secondary to the PD process. These findings may also have therapeutic implications. PMID- 8498827 TI - Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives. AB - We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1 5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3 14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5 18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation. PMID- 8498828 TI - Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson's disease. AB - Regional and global metabolic rates for glucose were estimated using 18F fluorodeoxyglucose and positron emission tomography in 10 patients with a clinical likelihood of striatonigral degeneration (2 men and 8 women; mean age, 61.8 +/- 6.9 years; mean disease duration, 4.7 +/- 2.2 years; mean Hoehn and Yahr score, 3.5 +/- 0.8). Measures of brain glucose metabolism in these patients were compared with those for 10 age-matched normal volunteers, 10 disease severity matched patients with Parkinson's disease (PD), and 10 disease duration-matched patients with PD. Normalized glucose metabolism was significantly reduced in the caudate (p < 0.03) and putamen (p < 0.003) as compared with that in normal and PD control subjects, and discriminated patients with striatonigral degeneration from control subjects (p < 0.002). Putamenal hypometabolism in patients with striatonigral degeneration correlated significantly with quantitative ratings of motor disability (p < 0.02). These results suggest that quantitative 18F fluorodeoxyglucose positron emission tomography techniques may be useful in supporting a diagnosis of striatonigral degeneration in life, and in objectively assessing disease severity and potential therapeutic interventions. PMID- 8498829 TI - Skew deviation with ocular torsion: a vestibular brainstem sign of topographic diagnostic value. AB - Fifty-six patients with unilateral brainstem infarctions presenting with skew deviation of the eyes were analyzed for static vestibular function in the roll plane. Ischemic lesions were allocated to the level and side of the brainstem by the clinical syndrome and neuroimaging. Two findings of clinical relevance were obtained: (1) All skew deviations were ipsiversive (ipsilateral eye was undermost) with caudal pontomedullary lesions and contraversive (contralateral eye was lowermost) with rostral pontomesencephalic lesions. (2) All skew deviations were associated with concomitant ocular torsion and tilts of subjective visual vertical toward the undermost eye. Thus, skew deviation or more correctly, ocular skew torsion is a sensitive brainstem sign of localizing and lateralizing value. Evidence is presented that the ocular skew torsion sign indicates a vestibular tone imbalance in the roll plane secondary to graviceptive pathway lesions. PMID- 8498830 TI - X-linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course. AB - An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before. PMID- 8498831 TI - Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors. AB - In patients with malignant gliomas, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) may discriminate tumor progression from radionecrosis. We evaluated data from 50 patients undergoing FDG-PET for suspicion of tumor progression. Forty-nine were treated with surgery, 48 with radiotherapy, and 37 with chemotherapy. Twenty-one had intensive radiotherapy with either three daily treatments in two 5-day periods and intravenous carboplatin (17) or interstitial brachytherapy or stereotactic radiotherapy. Twenty underwent surgery after magnetic resonance imaging/FDG-PET; 9 demonstrated increased uptake of FDG and evidence of tumor, whereas 6 had decreased uptake and no evidence of tumor. In 5 patients, there was no correlation (all had intensive radiotherapy). In 17 patients who received bromodeoxyuridine intravenously just before surgery, the bromodeoxyuridine labeling index corresponded to the histological appearance in all but 2 patients (both had received intensive radiotherapy). In 30 patients without surgery, decreased uptake of FDG suggested prolonged survival; increased uptake of FDG did not predict survival. Eight of 10 with intensive radiotherapy had decreased label uptake. We conclude FDG-PET for evaluation of patients with possible recurrent tumors requires more study. In patients with intensive radiotherapy, FDG-PET results cannot be correlated accurately with tumor progression. PMID- 8498832 TI - Systemic histiocytosis presenting as multiple sclerosis. AB - A patient resembling one with progressive multiple sclerosis in clinical presentation and by magnetic resonance imaging was studied in detail. Some features atypical for multiple sclerosis prompted a persistent search for an alternative cause. The diagnosis of a non-Langerhans systemic histiocytosis involving brain and bone was established and showed a partial response to radiation therapy. This patient illustrates the continued importance of a broad approach to the evaluation of possible multiple sclerosis, with particular attention to atypical features. PMID- 8498833 TI - Pretectal eyelid retraction and lag. AB - We report 2 patients who had eyelid retraction and eyelid lag with minimal impairment of vertical gaze. In both patients, magnetic resonance imaging demonstrated a circumscribed unilateral lesion immediately rostral and dorsal to the red nucleus involving the lateral periaqueductal gray area. Our clinical and radiological findings support the existence of a premotor eyelid control center in the region of the nucleus of the posterior commissure. PMID- 8498834 TI - Recurrent stroke caused by spondylotic compression of the vertebral artery. PMID- 8498835 TI - Immune-mediated demyelination. AB - The Guillain-Barre syndrome (GBS) and multiple sclerosis (MS) are thought to result from aberrant immune responses to myelin antigens. Recent evidence to implicate the cytokine tumor necrosis factor-alpha (TNF-alpha) and the intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of these disorders is reviewed. In GBS, elevated serum concentrations of TNF-alpha are detectable in 20 to 50% of patients. TNF-alpha released from autoreactive T cells, macrophages, or microglia may contribute to inflammatory demyelinative processes by upregulating the expression of recognition molecules on antigen-presenting cells; by cytotoxic damage to endothelium; by stimulating the secretion of inflammatory mediators; by directly injuring the myelin sheath; or by interfering with impulse propagation. Its pathogenic potential in GBS is underscored by findings in experimental autoimmune neuritis. Soluble ICAM-1, originating from T cells, macrophages, endothelium, or glial cells, circulates at increased concentrations in serum and cerebrospinal fluid of patients with active MS. ICAM-1 may be crucially involved in the migration of autoreactive T lymphocytes from blood to brain. Whether ICAM-1 can serve as a marker of acute inflammatory events in MS associated with clinical relapses warrants further investigation. TNF-alpha and ICAM-1 could be targets for antigen nonspecific treatment approaches to the inflammatory demyelinating diseases GBS and MS. PMID- 8498836 TI - Clinical determinants of dementia related to stroke. AB - Among 251 patients examined 3 months after the onset of acute ischemic stroke, we diagnosed dementia in 66 (26.3%) by using modified DSM-III-R criteria based on neuropsychological, neurological, functional, and psychiatric examinations. We used a logistic regression model to derive odds ratios (ORs) for clinical factors independently related to dementia in this cross-sectional sample. Dementia was significantly associated with age, education, and race. A history of prior stroke (OR = 2.7) and diabetes mellitus (OR = 2.6) was also independently related to dementia, but hypertension and cardiac disease were not. Stroke features associated with dementia included lacunar infarction compared with all other subtypes combined (OR = 2.7) and hemispheric laterality in relation to brainstem or cerebellar location. There was a predominance of dementia in patients with left-sided lesions (OR = 4.7), an effect not explained by aphasia. Dementia was especially common with infarctions in the left posterior cerebral and anterior cerebral artery territories. A major dominant hemispheral syndrome (reflecting size and laterality) was also independently associated with dementia (OR = 3.9). We suggest that dementia after ischemic stroke is a result of multiple independent factors, including both small subcortical and large cortical infarcts especially involving the left medial frontal and temporal regions, with additional contributions by demographic and vascular risk factors. PMID- 8498837 TI - Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. AB - The pathogenesis of the dementia associated with human immunodeficiency virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify any correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction in the brains from 24 HIV-infected patients with and without dementia and 9 HIV-uninfected control subjects. Levels of tumor necrosis factor-alpha messenger RNA were significantly higher and levels of interleukin (IL)-4 messenger RNA were significantly lower in demented compared to nondemented HIV-infected patients. Demented patients also had lower IL-1 beta levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL-6, transforming growth factor-beta 1 and -beta 2, monokine induced by gamma interferon-2 (MIG-2), or interferon gamma messenger RNAs. IL-10 and IL-2 messenger RNAs were undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV-positive patients were similar to those in HIV-negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor-alpha in the development of neurological dysfunction. Increased levels of tumor necrosis factor-alpha messenger RNA were not associated with increased levels of IL-1 beta messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498838 TI - Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? AB - Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiotherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with radiotherapy alone. The effect of neurosurgical excision plus radiotherapy was compared with radiotherapy alone in a prospectively randomized trial with 63 evaluable patients with systemic cancer and a radiological diagnosis of single brain metastasis. Radiotherapy was given to the whole brain by a novel scheme of 2 fractions per day of each 2 Gy for a total of 40 Gy. Before randomization, patients were stratified by site (lung cancer vs nonlung cancer) and status of extracranial disease (progressive vs stable). Survival as such and functionally independent survival (FIS; defined as World Health Organization performance status < or = 1 and neurological function < or = 1) were compared between both treatment arms. The combined treatment compared with radiotherapy alone led to a longer survival (p = 0.04) and a longer FIS (p = 0.06). This was most pronounced in patients with stable extracranial disease (median survival, 12 vs 7 mo; median FIS, 9 vs 4 mo). Patients with progressive extracranial cancer had a median overall survival of 5 months and a FIS of 2.5 months irrespective of given treatment. Improvement in functional status occurred more rapidly and for longer periods of time after neurosurgical excision and radiotherapy than after radiotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498839 TI - Elevated serum levels of tumor necrosis factor-alpha in Guillain-Barre syndrome. AB - Activated T lymphocytes and macrophages play a putative role in the the pathogenesis of Guillain-Barre syndrome. Both cell types secrete tumor necrosis factor-alpha, a cytokine that has well-recognized toxic effects on myelin, Schwann cells, and endothelial cells. We determined serum and cerebrospinal fluid concentrations of tumor necrosis factor alpha in 26 patients with Guillain-Barre syndrome, 27 patients with other polyneuropathies, 30 patients with neurological diseases of the central nervous system, and 14 healthy control subjects. Markedly increased serum levels were detected in 14 patients (54%) with Guillain-Barre syndrome and to a significantly lesser extent, in patients with other polyneuropathies (26%) and in neurological control subjects (23%). Tumor necrosis factor-alpha was not detected in the cerebrospinal fluid of patients with Guillain-Barre syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain-Barre syndrome correlated directly with disease severity and these concentrations returned to normal in parallel with clinical recovery. These findings emphasize the complexity of the immune response in patients with Guillain-Barre syndrome and suggest that tumor necrosis factor alpha may be important in the pathogenesis of peripheral demyelination in this disorder. PMID- 8498840 TI - Evidence for mitochondrial dysfunction in patients with alternating hemiplegia of childhood. AB - Phosphorus magnetic resonance spectra of resting muscle were obtained from 4 patients with alternating hemiplegia of childhood. All patients had abnormally high resonance intensities from inorganic phosphate and an abnormally low calculated cytosolic phosphorylation potential. Two of the 4 patients had abnormally low resonance intensities from phosphocreatine and an abnormally high calculated cytosolic free adenosine diphosphate concentration. These abnormalities are indicative of mitochondrial dysfunction. The combination of a central nervous system disorder and evidence of mitochondrial dysfunction in muscle suggests that alternating hemiplegia of childhood may represent a previously unrecognized phenotype of mitochondrial disease. PMID- 8498841 TI - The Golgi apparatus of motor neurons in amyotrophic lateral sclerosis. AB - The Golgi apparatus plays a key role in the posttranslational processing of polypeptides destined for secretion, incorporation into plasma membranes, and fast axoplasmic transport. Dispersion or fragmentation of the Golgi apparatus, experimentally induced by microtubule-disrupting agents, is associated with decreased secretion of immunoglobulins and insulin. The Golgi apparatus is also involved in targeting of lysosomal enzymes and in the endocytosis of certain hormones, receptors, and toxins. There is a paucity of information on this important organelle in human neuropathological conditions. Using an organelle specific antiserum we have examined by immunocytochemistry the Golgi apparatus of motor neurons in the spinal cord in 4 patients with amyotrophic lateral sclerosis and 1 patient with Werdnig Hoffmann's disease, 1 with infantile neuronal degeneration, 1 with adult-type familial bulbospinal atrophy, 1 with mitochondrial myopathy with cytochrome c oxidase deficiency, 1 with centronuclear myopathy, and 1 with Duchenne's muscular dystrophy, and in 9 age-matched control subjects. In all motor neuronopathies examined and in the patient with mitochondrial myopathy, 20 to 85% of neurons counted had "fragmented" Golgi apparatus. In age-matched control subjects and the other 2 patients with myopathies, 0 to 1.65% of motor neurons had fragmented Golgi apparatus. These findings suggest that the Golgi apparatus of motor neurons is involved in patients with amyotrophic lateral sclerosis and related motor neuron diseases, and perhaps in patients with certain fatal primary myopathies. PMID- 8498842 TI - Reduction of low-molecular-weight acid phosphatase activity in Alzheimer brains. AB - Recent studies in Alzheimer brains have shown aberrant protein phosphorylation, suggesting an alteration in protein kinases and/or phosphoprotein phosphatases. In the present study, the activity of acid phosphatase was investigated in samples prepared from postmortem normal human and Alzheimer brains. p-Nitrophenyl phosphate, a nonprotein phosphoester, was used as a substrate for acid phosphatase. The separation profile on Sephadex G-100 gel filtration chromatography revealed that two major forms of high-molecular-weight and low molecular-weight acid phosphatase were present in the crude extracts of both rat and human brains. Another class of zinc ion (Zn2+)-dependent acid p-nitrophenyl phosphatase was also detected in rat and human brains. In Alzheimer brains, the low-molecular-weight acid phosphatase activity was significantly decreased compared to that in control brains; however, the high-molecular-weight and Zn(2+) dependent acid phosphatase activity in control and Alzheimer brains was not different. These results suggest that reduced activity of the low-molecular weight acid phosphatase, which possesses phosphotyrosine protein phosphatase activity, might be linked to aberrant protein tyrosine phosphorylation found in Alzheimer brains. PMID- 8498843 TI - Amygdaloid sclerosis in temporal lobe epilepsy. AB - Hippocampal sclerosis is the sole abnormality found in approximately 65% of all temporal lobe specimens resected for intractable temporal lobe epilepsy. Up to 27% of en bloc temporal lobectomy specimens, however, show no definitive pathological changes. The lateral amygdaloid nucleus from 8 consecutive patients who underwent temporal lobectomy in whom no definitive hippocampal pathology was present and corresponding tissue from 8 consecutive patients with hippocampal sclerosis were subjected to quantitative estimation of neuronal density and astrogliosis. As compared to amygdaloid tissue from autopsy control subjects with no history of neurological disease, both the patient group with and that without hippocampal sclerosis consistently exhibited severe neuronal loss and gliosis with no quantitative differences between the two groups. Blinded clinical review of both groups of patients revealed that the development of hippocampal sclerosis was associated with a history of early brain insult; this history was absent in patients with isolated amygdaloid sclerosis. Neuropsychological testing prior to surgery demonstrated that patients with hippocampal sclerosis displayed a greater degree of memory impairment than did those without hippocampal sclerosis. We conclude that amygdaloid sclerosis occurs in the absence of hippocampal sclerosis, and that these patients form a distinct group with no history of early brain insult and milder memory impairment than that seen in patients afflicted with hippocampal sclerosis. PMID- 8498844 TI - Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis. AB - Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancestry is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non Scandinavian correlations may reflect predominantly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural environment, is part of the complicated picture of MS as a disease of place. PMID- 8498845 TI - Coexistence of hereditary motor and sensory neuropathy type Ia and IgM paraproteinemic neuropathy. AB - A patient with minimal motor dysfunction dating from early childhood developed more rapidly progressive distal weakness and positive sensory symptoms due to peripheral neuropathy in the fourth decade of life. DNA analysis showed the partial duplication of chromosome 17p associated with hereditary motor and sensory neuropathy type Ia. In addition, the patient had an IgM paraproteinemia and the typical morphological features of IgM paraproteinemic neuropathy on nerve biopsy. PMID- 8498846 TI - Molecular genetic characterization of an X-linked form of Leigh's syndrome. AB - We report a patient with necrotizing encephalomyelopathy (Leigh's syndrome) associated with a deficiency of pyruvate dehydrogenase complex activity. The underlying mutation is an A to C transversion in the pyruvate dehydrogenase complex E1 alpha subunit gene. As the E1 alpha subunit is encoded on the X chromosome, this observation confirms that some patients with Leigh's syndrome may potentially exhibit X-linked inheritance. PMID- 8498847 TI - Human leukocyte antigens in Fisher's syndrome. AB - We performed human leukocyte antigens (HLA) typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen. PMID- 8498848 TI - Clinical neurophysiology education in residency. PMID- 8498849 TI - Efficacy of felbamate monotherapy. PMID- 8498850 TI - [Rectal involvement secondary to prostatic adenocarcinoma]. AB - Rectal involvement secondary to adenocarcinoma of the prostate is uncommon and carries a poor prognosis. Distinguishing secondary from primary rectal tumors is mandatory, since each condition warrants a completely different treatment. There are at least five forms of clinicopathological involvement, depending on the rectal wall invasion and its consequences. We report on 6 cases, 4 had been diagnosed when rectal invasion was present, the enteric involvement appeared during the process in 1 patients and the other had prostate carcinoma coexisting with squamous cell carcinoma of the anus. PMID- 8498851 TI - [Chemotherapy in prostatic carcinoma]. AB - Carcinoma of the prostate has been treated by monochemotherapy, polychemotherapy, intraarterial chemotherapy, combined chemo and hormone therapy and growth factor antagonists. Difficulties exist in evaluating the efficacy of chemotherapy due to the scant number of patients treated and the different criteria used to assess response. Monochemotherapy has achieved a response rate (complete and partial) of less than 20% in randomized studies and that obtained with polychemotherapy is only slightly higher. The studies that have been conducted comparing these two treatment modalities have not clearly demonstrated the superiority of the latter. The duration of response is short and is measured in weeks. There is no standard treatment. Adriamycin, fluorouracil and cyclophosphamide appear to be the most effective cytostatic agents. There is no evidence that chemotherapy improves survivorship, and in comparison to symptomatic treatment, the former has been superior. The combination of chemotherapy with hormone therapy as a first line of treatment can improve the response rate slightly and enhance survivorship, although further studies are warranted to determine this definitely. Recruitment with androgens increases the response, but may entail risks. The growth factor antagonists have extended the therapeutic possibilities in prostate carcinoma, but further studies are warranted to determine its true value. PMID- 8498852 TI - [Treatment of ureteral stenoses with modelling catheter (12 Fr. caliber)]. AB - We present the results achieved by catheter dilatation in 31 cases of ureteral strictures of different etiologies, using a large caliber (12 Fr) double pigtail catheter. The patients had a mean follow up of at least two years. The catheter was left indwelling for 2 1/2 months. The success rate was 74.2%, with few and unimportant complications. However, in 3 cases with strictures of a tuberculous etiology the long-term success rate dropped to 33.3%. The results indicate that ureteral stents of a caliber larger than that used normally, increase the success rate in dilatation of ureteral strictures. PMID- 8498853 TI - [Echo-guided biopsy in renal transplant]. AB - A prospective study of 64 biopsies was undertaken to determine the efficacy of ultrasound-guided biopsy of renal grafts. All the biopsies were performed using real-time ultrasound guidance and a Tru-Cut biopsy needle. Sixty-two (97%) of the biopsies were diagnostic; a total of 85 punctions (mean 1.3) were performed. Forty-seven (73.4%) biopsies contained cortical issue, 15 (23.4%) cortical and medullary, and 2 (3.2%) medullary tissue alone. Mild hematuria was observed in 8 (12%) and there were no major complications. Four of the 8 cases (50%) with hematuria required dialysis, while the remaining 4 (50%) did not (p > 0.05). Concerning the type of tissue obtained and the complications, 5 (62.5%) of the patients whose biopsies contained medullary tissue presented complication (p < 0.05) ascribable to the depth of the punction. The mean number of biopsy punctions with hematuria was 1.5 (p < 0.05). In our view, ultrasound-guided biopsy is a highly effective technique for obtaining valid biopsy specimens of the renal graft, which reduces the risk of complications in this percutaneous procedure. PMID- 8498854 TI - [Paratesticular rhabdomyosarcoma: report of a case]. AB - A case of paratesticular rhabdomyosarcoma in a 17-year-old patient is described. The clinical features, diagnostic and therapeutic aspects of this rare tumor type are briefly discussed. PMID- 8498855 TI - [Bladder carcinosarcoma. Report of 2 cases]. AB - Two additional cases of this rare bladder tumor are described. The immunohistochemical analyses confirmed the histological diagnosis of this aggressive tumor type. The choice of treatment for the tumor and its metastasis is influenced by its rarity. PMID- 8498856 TI - [Carcinoma of the prostate metastasized to mandible simulating primary parotid tumor]. AB - We report a case of prostate carcinoma metastatic to the mandible that had been initially suspected as being a primary carcinoma of the parotid with lymph node metastasis. The present case underscores the diverse forms of manifestation of prostate carcinoma. PMID- 8498857 TI - [Adrenal pseudocyst: clinicopathologic study of a case]. AB - Herein we describe a case of a hemorrhagic adrenal pseudocyst that had been initially suspected as being a renal adenocarcinoma. The intraoperative anatomopathological study of the specimen permitted performing conservative surgery. The diagnosis and pathogenesis of this uncommon disease entity are discussed. PMID- 8498858 TI - [Leiomyoma of the female urethra]. AB - Leiomyoma of the urethra is a small, benign and extremely rare tumor of mesenchymal origin. To date, about thirty cases have been reported in the literature. A case of leiomyoma of the urethral meatus that had been incidentally discovered is described. The anatomopathological aspects are presented and the clinical and therapeutic problems are discussed. PMID- 8498859 TI - [Urinary tract involvement as the first clinical manifestation of adenocarcinoma of the colon]. AB - A patient with a previous history of left renal colic and no evidence of passing calculi was admitted to hospital for exacerbation of the urinary condition. The IVP and US evaluation revealed a ureteral stop which appeared to be extrinsic on retrograde uretero-pyelography. Surgery disclosed a large urinoma in the lumbar fossa. The compromised ureteral segment was removed and the pathological analysis of the surgical specimen revealed infiltration from adenocarcinoma. A primary tumor was sought early postoperatively due to irregular constipation referred by the patient. Finally, adenocarcinoma of the sigmoid colon was found. Only 8 similar cases of urinoma from extravasation due to ureteral obstruction secondary to a tumor have been reported in the literature up to 1982. PMID- 8498860 TI - [Gonadal stromal tumor in childhood. Report of a case. Comments]. AB - A case of testicular gonadal stromal tumor in an 8-month-old boy is described. Patient evaluation revealed no hormonal alterations. The patient underwent orchidectomy and has remained tumor-free at two years follow-up, which meets the well-established criteria for benign tumors. A detailed anatomopathological description is presented. PMID- 8498861 TI - Cyst of seminal vesicle with ectopic ureter and ipsilateral renal dysplasia: case report. AB - A case of ectopic ureter in a cystic seminal vesicle associated to a microkidney is presented. The diagnosis was established by history, physical examination, CT and direct contrastography by perineal access. Treatment consisted of excision of the cystic seminal vesicle with the ectopic ureter and dysplasic kidney. PMID- 8498862 TI - [Biographical sketch of Martin de Castellanos de Maudes]. AB - During the Renaissance and Baroque periods, when surgical specialization still remained in obscurity in Europe, Spanish Urology had already started to excel. The specialty, however, had not yet been institutionalized in our country and remained outside the pale of the Universities. But, as in a guild, the techniques were taught and learned, transmitted from teacher to student, and the interest of the Crown in institutionalizing and protecting the activities of these professionals was manifest. Of these, Martin de Castellanos de Maudes was renowned and became the first professor to hold the Chair of Urology in the history of medicine, and perhaps the most important surgeon of the Golden Age. He clearly deserves more recognition and should occupy his corresponding place among the pioneers of our specialty. PMID- 8498863 TI - [Preservation of the bladder neck fibers in radical prostatectomy]. PMID- 8498864 TI - Comparative studies of the induction of erectile response to film and fantasy in diabetic men with and without neuropathy. AB - The present study deals with the diabetic neuropathies prevailing in men. In this investigation 100 insulin-dependent diabetes mellitus (IDDM) and 314 non-insulin dependent diabetes mellitus (NIDDM) patients with and without an objective evidence of neuropathy, having an age span in between 15 and 60 years and a duration of diabetes distributed over 1-33 years, were included along with their age-matched nondiabetic controls. The diabetic subjects were evaluated for the induction of erectile responses. Investigation of induction of erectile responses to erotic stimulation by film and fantasy revealed striking results in diabetic patients with established neuropathy. Both IDDM and NIDDM patients with neuropathy exhibited a highly significant decrease (P < .0005) in penile diameter and length, penile arterial pulse amplitude, both systolic and diastolic blood pressures, and heart rate compared to controls of the same age group. However, both IDDM and NIDDM patients without neuropathy showed a nonsignificant difference in the above-mentioned parameters compared to control subjects. A nonsignificant association of induction of erectile responses to erotic stimulations among IDDM and NIDDM patients with and without neuropathy was also observed, suggesting that impotence and altered erectile responses are likely to be associated with an increased frequency to autonomic neuropathy in these patients irrespective of their type of diabetes. PMID- 8498865 TI - Late gonadal function and autoimmunization in familial testicular torsion. AB - Testicular torsion, one of the most common pediatric urological emergencies, is rarely familial. This study deals with the sixth recorded family with familial testicular torsion and the effects on the spermatogenesis and the appearance of testicular autoantibodies in three affected subjects (two brothers, aged 18 and 15 years, and their father, aged 48 years). The father and one of the brothers, who had peripubertal unilateral testicular torsion, presented normal fertility and oligozoospermia, respectively. The other brother, who had a history of bilateral testicular torsion, did not present pubertal development until he was 18 years old and he needed substitutive testosterone therapy. Sperm autoantibody titer increased only in the two cases with unilateral torsion and remained unmodified at a 5-year follow-up. The results indicate that testicular torsion can cause variable degrees of spermatogenesis impairment and induce development of autoantibodies against spermatozoa and gonadal antigens. The persistence of fertility in the father and the progressive spermatogenesis recovery in one of the affected sons suggest that the damaging effects of these autoantibodies deserve further investigation. PMID- 8498866 TI - Retrograde ejaculation accompanying hyperprolactinemia. AB - A patient, 38 years of age with 10 years of infertility, suffered from an ejaculation disorder for 2 years. Based on a diagnosis of retrograde ejaculation, sperm retained in the bladder was collected and homologous artificial insemination was carried out, but pregnancy was not achieved. The subject was examined at the Department of Urology and hormone tests were conducted showing hyperprolactinemia, hypogonadotropinemia, and hypotestosteronemia. A CT scan showed a pituitary tumor. Administration of 7.5 mg/day of bromocriptine was initiated to treat this tumor. Antegrade ejaculation recurred 1 month after administration, and pregnancy was achieved from normal sexual intercourse 5 months after administration. PMID- 8498867 TI - Treatment of varicocele and male fertility. AB - Ninety-six patients with varicocele were followed for 4 years in a prospective randomized study. Seventeen patients were excluded from the study in accordance with exclusion criteria. In 26 patients varicocele was treated surgically and 12 patients were treated either by sclerosation or embolization. Forty-one patients with varicocele had no therapy. In 54 patients oligoasthenozoospermia and in 25 normozoospermia was certified. In the group of patients without treatment, the pregnancy rate in the women was higher (22/41, or 53.7%) than in the group receiving treatment (13/38, or 34.2%). The difference was not statistically significant. After therapy, sperm concentration increased and sperm motility improved also. The differences were not statistically significant. The study showed that varicocele therapy bears no influence on male fertility. PMID- 8498868 TI - Orosomucoid levels in the seminal plasma or fertile and infertile men. AB - Orosomucoid levels were measured in the seminal plasma of 185 men divided in a) twelve groups according to etiological diagnosis of infertility and b) two groups on the basis of the normal or abnormal spermiogram. There was no significant difference of the concentration of seminal plasma orosomucoid between the controls and the patients of the other groups. There was no correlation between seminal plasma orosomucoid concentration and sperm concentration, as well as between seminal plasma orosomucoid level and sperm motility. The evaluation of orosomucoid in the seminal plasma is not of diagnostic value in the workup of male infertility. PMID- 8498869 TI - Concentrations of intracellular sex steroids in human spermatozoa. AB - In an attempt to determine whether human spermatozoa contain steroid hormones, the immunoreactive levels of progesterone, testosterone, and estradiol-17 beta were measured in the extracts of sonicated specimens of sperm obtained as ejaculates from husbands of infertile couples (n = 67, age 26-44 years). In the range of sperm concentration between 3.0 and 869.6 million per ejaculate (143.2 +/- 13.6 mean +/- SEM), the concentrations were as follows: progesterone 127.3 6685.4 fmol/ml (1434.5 +/- 178.6), testosterone 98.3-2219.1 fmol/ml (611.6 +/- 49.0), and estradiol-17 beta 33.0-678.1 fmol/ml (206.9 +/- 19.7). Using Pearson's correlation coefficient, the steroid hormone levels correlated significantly with the total sperm number (p < .02). The spermatozoa contained small but measurable amounts of the sex steroids. PMID- 8498870 TI - Tail beat frequency of human sperm: evaluated with sperm head fixation method and computer-assisted semen analysis. AB - Tail beat frequency (TBF) of individual sperm in 15 semen samples was evaluated with a sperm head fixation method (SHFM). Motility parameters of the semen samples were also measured with computer-assisted semen analysis (CASA). The TBF obtained from SHFM correlated best with beat cross-frequency obtained from CASA. The TBF measured soon after sperm head fixation also correlated well with total motility and rapid motility, but not with progress motility and critical motility measured with CASA. SHFM is a simple method for the study of tail beat frequency and the TBF of individual sperm is closely related to the overall motility in a semen sample. PMID- 8498871 TI - Effect of heparin on human spermatozoa migration in vitro. AB - In an in vitro model, the number of human sperm cells migrating to wells containing heparin was significantly higher than those migrating to control wells. In humans a statistically significant chemotactic effect was noted in a 0.05 mg/ml in incubation medium. PMID- 8498872 TI - Effect of early antibiotic treatment on the formation of sperm antibodies in experimentally induced epididymitis. AB - This investigation was conducted to evaluate whether or not experimentally produced epididymitis could induce the development of cytotoxic sperm antibodies and if effective antibiotic therapy could reverse the development of immunity to sperm. Escherichia coli was injected into the tail of the epididymis in adult Lewis rats to induce epididymitis and was allowed to incubate for 24 h, 72 h, 8 days, or 15 days. Serum titers of cytotoxic sperm antibodies at these time intervals were determined. Sperm antibody titers began to rise 3 days after inoculation, peaked, and plateaued at 8 days. The titers were negligible in the control rats. Two other groups of rats were inoculated with E. coli in a similar manner and were treated with tetracycline 25 mg/kg/day starting at either 24 h or 8 days after inoculation, for 7 days. The antibody titers became negligible in these two treated groups, the results being statistically significant when contrasted with the infected but untreated groups (p < .001 and < .05, respectively, for the 24-h and 8-day groups). However, histological examination of the antibiotic-treated and untreated specimens revealed significant inflammation and infection of the epididymis in both treated groups. Testicular alterations were consistent in both groups. It is concluded that epididymitis consequent to infection with E. coli can induce cytotoxic antibody formation in Lewis rats. Treatment with appropriate antibiotics may suppress the antibody response either through a direct immunosuppressive effect of the antibiotic or through a decrease in the antigenic load of killed sperm secondary to eradication of the infection. PMID- 8498873 TI - Variation in antisperm antibody response following transection of male genital tract in Lewis rats. AB - Genital tracts of male Lewis rats were transected at various levels to determine whether this may influence antisperm antibody response. Adult male rats underwent bilateral transection of the vas deferens (group I, n = 9), mid-epididymis (group II, n = 10), and efferent duct (group III, n = 9). Group IV (n = 10) underwent a sham operation. Sera were collected by retro-orbital puncture before the operative procedure and monthly for 3 months postprocedure. Sperm-reactive immunoglobulins IgG, IgA, and IgM were measured individually as well as combined in serum by enzyme-linked immunosorbent assay (ELISA) using lithium diiodosalicylate (LIS)-solubilized washed rat caudal epididymal sperm. The maximal immune response was seen in all groups at 2 months postprocedure. Antibody response defined as the net ELISA absorbance reading for the combined immunoglobulin group were (mean +/- SEM): group I = 120 +/- 16, group II = 156 +/ 23, group III = 190 +/- 20, and group IV = 116 +/- 22. The highest antibody response was noted in the efferent duct group, which was statistically (p < .05) greater than the sham-operated and vas deferens groups. In the efferent duct group the highest immunoglobulin response was observed in the IgG class, which was significantly higher (p < .05) than the IgA and IgM classes. The transection of the male genital tract at different levels leads to variation in antisperm antibody response and that sperm located at different sites along the genital tract may differ in their autoantigenic potential. PMID- 8498874 TI - Microinjection of human sperm into perivitelline space of hamster eggs: comparison with zona-free hamster egg penetration of human sperm. AB - Micromanipulation of human sperm and oocyte has been utilized to facilitate fertilization of those patients with male factor due to oligoasthenospermia or those patients with repeated fertilization failure in an in vitro fertilization (IVF) program. Before manipulating human gametes, one needs experience with animal models. Our objective was to perform subzonal insertion of human sperm into hamster eggs and to compare the result with that of sperm penetration assay (SPA) using zona-free hamster eggs. Semen samples were obtained from 15 fertile donors with normal semen analysis and the motile sperm were collected by swim-up procedure. Microinjection was performed by injecting a varied number of sperm into the perivitelline space of 222 hamster eggs pretreated with sucrose solution (0.1 M). The rate of damage of eggs during microinjection was 7.2% (16/222). The rates of penetration in the microinjection group were 5.1% (4/79) for 1-5 sperm injected, 10.9% (11/101) for 6-10 sperm injected, and 11.5% (3/26) for 11-15 sperm injected. The average rate of penetration per egg was 8.7% (18/206), and the polyspermic rate was 11.1% (2/18). Simultaneously SPA was performed in each sample of semen as a positive control, and the average rate of penetration of SPA was 51.4% (108/210). The rate of penetration in the microinjection group was significantly smaller (p < .05) than that in the SPA group. Whether the penetration rate and polyspermic rate in a hamster model reflect similar results in human oocyte requires further investigation. However, the hamster egg provides an ideal model to develop a micromanipulation technique for human beings. PMID- 8498875 TI - Testicular compression during exercise: serum testosterone levels. AB - Serum testosterone levels are increased in athletes after short-term exercise. To investigate whether mechanical compression could contribute to this increase, we subjected 14 male volunteers to mechanical testicular compression via a pneumatic cuff. The serum testosterone levels were sampled at time intervals before, during and after compression. There was a rise in mean serum testosterone levels of 16.7 18.2%, with a maximal increase at 1.5 min after compression was released. Mechanical compression alone did not explain the rise in serum testosterone, although it may have a contributory role. PMID- 8498876 TI - Psychotherapy and bulimia nervosa. Longer-term effects of interpersonal psychotherapy, behavior therapy, and cognitive behavior therapy. AB - OBJECTIVE: To determine whether cognitive behavior therapy (CBT) for bulimia nervosa has a specific therapeutic effect and determine whether a simplified behavioral treatment (BT) of CBT is as effective as the full treatment. DESIGN: Randomized controlled trial involving three psychological treatments. Two planned comparisons, CBT with interpersonal psychotherapy (IPT), and CBT with BT. Closed 12-month follow-up period. Independent assessors. SETTING: Secondary referral center. PATIENTS: Seventy-five consecutively referred patients with bulimia nervosa. Patients with concurrent anorexia nervosa were excluded. INTERVENTIONS: Cognitive behavior therapy, IPT, BT conducted on an individual outpatient basis. There were nineteen sessions over 18 weeks. Six experienced therapists administered all three treatments. There was no concurrent treatment. MAIN OUTCOME MEASURE: Frequency of binge eating and purging. RESULTS: High rate (48%) of attrition and withdrawal among the patients who received BT. Over follow-up, few patients undergoing BT met criteria for a good outcome (cessation of all forms of binge eating and purging). Patients in the CBT and IPT treatments made equivalent, substantial, and lasting changes across all areas of symptoms, although there were clear temporal differences in the pattern of response, with IPT taking longer to achieve its effects. CONCLUSIONS: Bulimia nervosa may be treated successfully without focusing directly on the patient's eating habits and attitudes to shape and weight. Cognitive behavior therapy and IPT achieved equivalent effects through the operation of apparently different mediating mechanisms. A further comparison of CBT and IPT is warranted. The behavioral version of CBT was markedly less effective than the full treatment. PMID- 8498877 TI - A 2- to 7-year follow-up study of 54 obsessive-compulsive children and adolescents. AB - OBJECTIVE: Due to the generally poor prognosis previously reported for patients with obsessive-compulsive disorder (OCD), this report systematically assessed the outcome of patients who had had access to new psychopharmacologic treatments to determine whether there had been any long-term gains and if there were any predictors of outcome. DESIGN: Prospective follow-up study of a cohort of consecutive pediatric patients with OCD who had participated in controlled treatment (clomipramine hydrochloride) trials and then received a variety of interim treatments. PATIENTS: Fifty-four children and adolescents were reevaluated 2 to 7 years (mean, 3.4 +/- 1.0 years) after initial clomipramine treatment. Information for 48 (89%) of the patients was from direct interview and for the remaining six (11%) from at least two sources. RESULTS: On follow-up, 23 of the subjects (43%) still met diagnostic criteria for OCD, and only three (6%) could be considered in true remission. Thirty-eight subjects (70%) were taking psychoactive medication at the time of follow-up. Although OCD symptoms continued, the group as a whole was significantly improved at follow-up, with only 10 subjects (19%) rated as unchanged or worse. A worse OCD outcome score at follow-up was predicted in a stepwise multiple regression by (1) more severe OCD symptoms score after 5 weeks of clomipramine therapy, (2) lifetime history of a tic disorder, and (3) presence of parental Axis I psychiatric diagnosis (R2 = .31, P < .01). CONCLUSIONS: With new treatments available, most patients with pediatric OCD can expect significant longterm improvements but not complete remission. This study supports previous reports of the chronicity and intractability of the disorder, as there still remained a significant subgroup of subjects who exhibited continued morbidity despite multiple interventions. PMID- 8498878 TI - A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. AB - OBJECTIVE: To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. DESIGN: Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. SETTING: Outpatient clinic. PATIENTS: A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. MEASURES: Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. RESULTS: Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. CONCLUSION: Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored. PMID- 8498879 TI - Outcome after rapid vs gradual discontinuation of lithium treatment in bipolar disorders. AB - OBJECTIVE: Withdrawal of bipolar mood disorder (BP-I) patients from prolonged, stable lithium maintenance has a high risk of early recurrence, particularly of mania. We thus compared risks of stopping lithium rapidly vs gradually. DESIGN: Outpatients undergoing clinically determined discontinuation of lithium treatment at different rates were followed up prospectively to 5 years. Risks and timing of new episodes were analyzed. PATIENTS: Subjects (N = 64) with a DSM-III-R BP disorder, previously stable on lithium monotherapy for 18 to 120 months (mean, 3.6 years) were followed up clinically after discontinuing lithium (elected in prolonged wellbeing in 67%). None was unavailable for follow-up, and subtyping (BP-I or BP-II) remained stable. RESULTS: Within 5 years, 75% had a recurrent episode; BP-I patients were 1.5-times less likely than BP-II to remain in remission. Polarity of first-recurrent and onset episodes was 80.8% concordant. Overall risk of a new episode of mania was significantly greater after rapid (< 2) than gradual (2 to 4 weeks discontinuation (5-year hazard ratio = 2.8); the difference in risk of depression was even greater hazard ratio = 5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio = 5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio = 4.3) than at later times (2 to 5 years), when courses of "survival" over time were nearly parallel in both discontinuation groups. CONCLUSIONS: Risk of early recurrence of BP disorder following discontinuation of lithium maintenance is elevated, but may be both predictable (timing and polarity) and modifiable by gradual discontinuation. PMID- 8498880 TI - A prospective follow-up of patients with bipolar and primary unipolar affective disorder. AB - OBJECTIVE: As part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression, the comparative course of manic depressive (bipolar) and primary unipolar patients was assessed. DESIGN: Systematic evaluation using structured instruments every 6 months for a period of 5 years with the recording of remissions, new episodes, and subsequent hospitalizations. PATIENTS: The number of subjects varied somewhat depending on the analyses conducted. For a comparison of course in bipolar patients and unipolar patients, 148 bipolars were compared with 172 unipolar patients. RESULTS: Both unipolar and bipolar patients were more likely to have episodes if they had episodes prior to index admission. Likewise, prior hospitalizations predicted multiple hospitalizations in follow-up. Chronicity was significantly more prevalent among unipolar depressives but in both unipolar and bipolar patients, chronicity diminished over time. Bipolar patients were more likely than unipolar patients to have multiple episodes at the 2-year and 5-year follow-ups. In bipolar patients, there was no difference in the number of episodes in follow-up between males and females but in unipolar patients, females were significantly more likely to have subsequent hospitalizations and episodes than males. Treatment variables did not relate to these differences. A family history of mania or schizoaffective mania predicted multiple episodes in bipolar patients but not in primary unipolar depressives. A family history of all affective illness (mania, schizoaffective mania, bipolar II illness, and depression) did not predict a multiple-episode course in either bipolar or unipolar illness. In unipolar patients, the independent variables leading to multiple-episode course in follow-up are being female, an early age of onset, and prior episodes. CONCLUSIONS: As a result of this systematic follow-up study, new data add to the distinction between bipolar and primary unipolar patients both as regards number of episodes in follow-up and also as regards risk factors that are associated with the multiple-episode course. PMID- 8498881 TI - Alprazolam in the treatment of premenstrual syndrome. A double-blind, placebo controlled trial. AB - OBJECTIVE: To evaluate the efficacy of alprazolam in the treatment of premenstrual syndrome. DESIGN: A randomized, double-blind, placebo-controlled, crossover trial of alprazolam during eight menstrual cycles. SETTING: Outpatient clinic at the National Institute of Mental Health, Bethesda, Md. PARTICIPANTS: Twenty-two women with prospectively confirmed premenstrual syndrome entered this study. All subjects were either self-referred or were referred by their physicians. All reported having regular menstrual cycle lengths, were taking no medication, and were free of current or recent medical or psychiatric illness. Two subjects did not complete the trial. INTERVENTION: Participants were assigned to receive alprazolam or placebo as follows: cycle 1, 0.25 mg of alprazolam or placebo three times daily beginning on menstrual cycle day 16; cycle 2, 0.50 mg of alprazolam or placebo three times daily according to the regimen during the first cycle; cycles 3 and 4, 0.75 mg of alprazolam or placebo three times daily from menstrual cycle day 16 and continued throughout the fourth menstrual cycle to evaluate the efficacy of relatively long-term (approximately 6 weeks) treatment with alprazolam. MAIN OUTCOME MEASURES: Daily self-report symptoms ratings were completed during the entire study period. RESULTS: We observed no significant differences in the severity of premenstrual symptom ratings during alprazolam administration compared with placebo on any scale except the Beck Depression Inventory Scale. The Beck Depression Inventory ratings demonstrated a statistically (F1,19 = 7.1, P < .05), but not clinically, significant improvement in depressive symptoms during alprazolam administration compared with placebo. CONCLUSION: Our findings do not support alprazolam as a uniformly effective treatment for the symptoms of premenstrual syndrome. PMID- 8498882 TI - Rapid eye movement sleep eye movements in schizophrenia and depression. AB - OBJECTIVE: To investigate the specificity of rapid eye movement (REM) sleep eye movement measures in schizophrenics, depressives, and nonpsychiatric controls. DESIGN: Survey. SETTING: Inpatient psychiatric hospital. STUDY PARTICIPANTS: Volunteer sample of male veterans who met Research Diagnostic Criteria (RDC) for schizophrenia (n = 21) or major depressive disorder (n = 24), or male veterans recruited from the community with no history of psychiatric illness (n = 13). Patients with a concurrent RDC diagnosis of alcoholism were excluded. After data collection, three schizophrenics, two depressives, and one nonpsychiatric control were eliminated because of two or fewer REM periods on either of the two recording nights. INTERVENTION: None. MAIN OUTCOME MEASURE: Computer-detected total night and within-night measures of REM sleep eye movement density, ie, the ratio of eye movement counts to stage REM minutes. RESULTS: Using a 95% confidence interval, schizophrenics, depressives, and nonpsychiatric controls did not differ in total night or within-night measures of eye movement density. Within nights, eye movement density increased across REM periods in the schizophrenics and nonpsychiatric controls; the depressives showed a flatter within-night distribution associated with their older age. CONCLUSIONS: A broad range of REM sleep eye movement densities characterize both schizophrenics and depressives and substantially overlaps the normal range. Abnormalities of REM sleep eye movement activity should not be considered a biological marker for affective illness. PMID- 8498883 TI - Clinical practice guidelines. Good news, bad news, or no news? AB - Clinical practice guidelines for primary care providers that address the detection, diagnosis, and treatment of depression may have an impact on psychiatric practice as well as on general medical education and the research agenda. This commentary highlights the conceptual and scientific issues that surrounded the development of these guidelines and speculates on their potential practical impact, particularly on psychiatry. PMID- 8498884 TI - Clinical psychopharmacologic practice. The need for developing a research base. AB - The advent of psychotropic drugs has enormously improved psychiatric care. Nonetheless, our practice is not optimum. Current knowledge is not regularly applied. It has been repeatedly shown that the majority of patients with psychiatric illness go undiagnosed, and even if diagnosed, they are inappropriately or ineffectively treated, both by clinical psychiatrists and by primary care practitioners. Improved care depends on practitioner education, often referred to as "technology transfer." PMID- 8498885 TI - Can antidepressants induce rapid cycling? PMID- 8498886 TI - Can antidepressants induce rapid cycling? PMID- 8498887 TI - Can antidepressants induce rapid cycling? PMID- 8498888 TI - Single photon emission computed tomography in obsessive-compulsive disorder. PMID- 8498889 TI - A neuroanatomy of obsessive-compulsive disorder. PMID- 8498890 TI - [A study on the prevalence of bronchial asthma in school children in western districts of Japan--comparison between the studies in 1982 and in 1992 with the same methods and same districts. The Study Group of the Prevalence of Bronchial Asthma, the West Japan Study Group of Bronchial Asthma]. AB - The prevalence of bronchial asthma in school children was examined both in 1982 (55,388 children) and in 1992 (45,674 children) in 11 western districts of Japan. Both studies were conducted with the same Japanese version of a modified ATS-DLD children's questionnaire in the same districts. RESULTS: 1) The study in 1992 established a prevalence rate of 5.6% in males and 3.5% in females with an overall average of 4.6%, which was 1.4 times higher than that of 10 years ago. The higher prevalence was observed in every grade of school children and in all districts. 2) The study in 1992 showed no differences based on the grades of the school children were in. The prevalence rate in males was 1.6 times higher than that in females with fewer regional differences than in the 1982 study. 3) Higher prevalence rates were found in those who had histories of respiratory diseases during their infancy, family histories of allergic disease or who lived in urban areas. The prevalence rate was 13.3% in children living in urban areas with family histories of bronchial asthma. 4) The prevalence rate of wheezing was 5.2%, which was 1.3 times higher than that of 10 years ago. The rate had increased in every district, but it decreased as the children moved into higher grades. PMID- 8498891 TI - [Effect of thromboxane receptor antagonist, BAY u 3405 on the late phase pulmonary response in guinea pigs]. AB - The effect of the specific thromboxane (Tx)A2 receptor antagonist, BAY u 3405 on the late asthmatic response (LAR) was investigated in guinea pigs which are sensitized actively with Ascaris suum antigen. Respiratory resistance (Rrs) of awake guinea pigs was measured by 30 Hz oscillation method for 6 hours after antigen challenge. %Rrs was calculated as the increase rate of Rrs to baseline Rrs (pre-challenge value). Ten mg/kg of BAY u 3405 or vehicle (0.5% methyl cellulose) was administered orally after the end of immediate asthmatic response, i.e., 2 hours after antigen challenge. %Rrs of the control group at 4 and 5 hours after antigen challenge were 101.4 +/- 27.5% and 77.5 +/- 19.9%, respectively. Those of the BAY group were 32.5 +/- 6.2% and 23.5 +/- 5.0%, respectively. %Rrs of the BAY group were significantly lower than those of the control group at both timings (p < 0.05). No significant difference was shown between the BAY group and the control group in the results of the bronchoalveolar lavage (BAL) 4 hours after challenge. Concerning the results of BAL at 6 hours after challenge, the total cell count and its segment, eosinophils count and lymphocytes count in the BAY group were 274.9 +/- 70.5, 62.5 +/- 13.1, 11.3 +/- 3.3 (x 10(5) cells), respectively, resulting in significantly smaller numbers (each p < 0.05) than those in the control group which were 491.9 +/- 55.1, 198.6 +/- 43.9, 32.1 +/- 7.3 (x 10(5) cells), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498892 TI - [Results of 29-year study of hoya (sea-squirt) asthma in Hatsukaichi, Hiroshima prefecture]. AB - As remarkable improvements have been made to the working environment and working methods of oyster shucking workers during the past 30 years, a study was made on the effects of these improvements on hoya (sea-squirt) asthma and the following results were obtained. 1) The prevalence of hoya (sea-squirt) asthma among oyster shucking workers was 36.0%, 30.1%, 21.7%, 22.0%, 18.0%, and 26.6% in 1963, 1968, 1976, 1984, 1988, and 1992, respectively. Accompanying the improvements made to the working environment and working methods, asthmatic symptoms failed to develop in some of the patients through engaged in oyster shucking work. Thus, those with symptoms actually accounted for 36.0%, 18.7%, 15/8%, 7.4%, 8.4%, and 8.0% of the workers, respectively. 2) The proportion of serious cases among the patients rapidly decreased from 29.2% in 1963 to 0% after 1984. On the other hand the proportion of slight cases was 35.4% in 1963, but after 1988 all the cases were slight cases. 3) During the period from 1984 to 1992, the number of those newly engaged in oyster shucking work was 74. The number of those who developed hoya (sea-squirt) asthma during this period was 8 or 10.1%. All the cases were asthma of the rhinitis type. 4) The number of workers who did not develop asthmatic symptoms though engaged in oyster shucking work was 53 in 1984, 40 in 1988, and 49 in 1992. Of this number, 31% are now under hyposensitization therapy, 57.0% have received this therapy in the past, and 12.0% have not received any therapy. PMID- 8498893 TI - Clinical effects of complex spa therapy on patients with steroid-dependent intractable asthma (SDIA). AB - The clinical effects of spa therapy (swimming training in a hot spring pool+inhalation of iodine salt solution+fango therapy) were examined in 52 patients with steroid-dependent intractable asthma (SDIA). Clinical effects were found in 36 of the 52 (69.2%) patients with SDIA. The efficacy was higher in the patients between the ages of 41 and 50 (87.5%) and between 51 and 60 (84.2%) than in those in the other age groups. Regarding clinical asthma types, the efficacy of spa therapy was higher in patients with type Ia-2 (83.4%), type Ib (77.8%) and type II (80.0%) than in those with type Ia-1 (54.2%). Efficacy seemed to be related to airway inflammation: the proportion of neutrophils and eosinophils in bronchoalveolar lavage (BAL) fluid was higher in patients with marked and moderate improvement compared with those with slight and no improvement. Ventilatory function was improved by complex spa therapy. %MMF and %V25 values increased by more than 20% after therapy in patients with type Ia-2, Ib and II asthma. Bronchial hyperreactivity to methacholine was suppressed after therapy. Any decreased function of the adrenocortical glands expressed by low serum cortisol levels improved after therapy, accompanied by a reduction in the dose of glucocorticoids necessary to control asthma attacks. PMID- 8498894 TI - [The effect of fluticasone propionate topically dosed prior to the pollen scattering season on cellular infiltration into the surface of nasal mucous membrane in patients with Japanese cedar pollinosis]. AB - In order to examine fluticasone propionate's mechanism of inhibiting nasal allergic symptoms, topical dosing of FP to patients with Japanese cedar pollinosis was started before the pollen scattering season, and the kinetics of basophilic cells and eosinophils which infiltrated into the surface of nasal mucous membrane were observed. Patients with Japanese cedar pollinosis were divided into two groups. Before and in the early period of the pollen scattering season, one group received FP and the other group a placebo, topically into the nostrils. In the mid and late season, both groups were treated with FP topical dosing. The study was carried out in the double blind manner. In the pre-, early and late season, specimens were scraped from the nasal mucosal surface, basophilic cell and eosinophil counts in the specimens were measured, and histamine and ECP contents in the specimens were also determined. Topical use of FP starting pre-season significantly inhibited symptoms of Japanese cedar pollinosis, as well as accumulation of basophilic cells and eosinophils in the nasal mucosal surface. Histamine and ECP contents in the nasal specimens tended to decrease with the topical use of FP. PMID- 8498895 TI - [Effect of capsaicin on the migration of eosinophils into the bronchi of guinea pigs]. AB - Substance P (SP), a potent neuropeptide, which is localized in the sensory nerves and released by many physiological stimuli has been implicated in airway neurogenic inflammation. We have studied the effects of capsaicin (CAP), which releases tachykinins (TK) from the sensory nerves, on eosinophil (EOS) recruitment in the airway in guinea pigs in vivo. Male guinea pigs were used. The respiratory resistance (Rrs) of the guinea pigs were measured by an oscillation technique and histological studies of the right main bronchus were carried out. Exposure to inhaled CAP resulted in a significant increase in Rrs with PC200 CAP of 0.97 +/- 0.25 (x 10(-6) M) (n = 5). This stimulation also provoked striking eosinophilia in the right bronchus in a dose-dependent manner. A neutral endopeptidase (NEP) inhibitor, phosphoramidon, potentiated CAP-induced EOS infiltration. By contrast, pretreatment with [D-Pro2, D-Trp7,9]-SP, an analogue of SP and its receptor antagonist, diminished the response. We conclude that CAP induced tachykinin release is capable of causing striking eosinophilia in the lung in vivo. This mechanism may contribute to airway inflammation in patients with asthma. This would provide further support for a link between tachykinin and bronchial eosinophilia in asthma. PMID- 8498896 TI - [Role of opioid peptide in rheumatoid arthritis--detection of methionine enkephalin and leucine-enkephalin in synovial tissue]. AB - A relationship between rheumatoid arthritis (RA) and endocrinological abnormality has been suspected for many years. In the present study, we immunohistologically identified the presence of methionine-enkephalin (Met-enk) and leucine-enkephalin (Leu-enk), in synovial tissues collected from RA patients and determined the amount of these peptides and interleukin 1 beta (IL-1 beta) in the culture supernatant of tissue explants by RI and ELISA. Synovial membrane samples obtained by biopsy during artificial joint replacement and plasma samples simultaneously collected from 11 RA patients (11 joint) diagnosed as having classic or definite RA according to the diagnostic criteria of the American Rheumatism Association were used. All 11 patients were females and aged between 36 and 64 years (mean: 45.8 years). As a result of immunohistological standing (ABC method), Met-enk was detected in vascular endothelial cells and Leu-enk in superficial cells, vascular endothelial cells and interstitial cells. Leu-enk concentrations (42.3 +/- 15.8 pg/ml) were higher in the culture supernatant of the synovial membrane than in the plasma (20.7 +/- 13.3 pg/ml). Furthermore, in the culture supernatant the concentration of Leu-enk was positively correlated with that of IL-1 beta (r = 0.789). These findings suggest that Met-enk and Leu enk are locally produced by synovial tissues and may exert an immunological and/or inflammatory role in RA synovitis. PMID- 8498897 TI - [Morphology and function of intra-hepatic lymphocytes derived mast cells]. AB - We have examined the functional characteristics of mast cells grown in tissue culture from intra-hepatic lymphocytes of mice (IHL-MC) and compared them with mast cells grown from bone marrow (BMC-MC). Intrahepatic lymphocyte derived mast cells had the functional characteristics of cultured mast cells. These cells were stained by alcian blue, had a lower histamine content than rat peritoneal mast cells (considered to be a model of connective tissue type mast cells) and responded to Ca2+ ionophore and IgE receptor mediated stimulation. However, there were some differences between IHL-MC and BMC-MC. IHL-MC had a higher histamine content and lower growth activity by T-cell derived factor than BMC-MC. PMID- 8498898 TI - [5th spring meeting of the Japanese Society of Allergology. Tokyo, Japan. May 27 28, 1993. Abstracts]. PMID- 8498899 TI - Multicenter study with recombinant human erythropoietin. AB - A multicenter study with recombinant human erythropoietin (rh-EPO) was carried out. Of 172 hemodialysis patients with anemia selected for the study from 20 hospitals and clinics, 77 were males and 95 females (mean age 53.9 years). A starting dose of 1,500 U of rh-EPO (Epoetin beta) was administered intravenously at the end of every dialysis session. If the efficacy was not acceptable, the dose was increased to 3,000 U. When the target hematocrit was achieved (30%), the total dose was decreased. The results of the study were excellent relative to those of other multicenter studies with regard to efficacy, safety, and changes in laboratory data. The incidence of hypertension was lower in our study compared with other reports because we used a low initial dose. The efficacy of rh-EPO therapy was determined earlier and more reliably by reticulocytes than by hematocrit or hemoglobin. Prompt iron supplement therapy is recommended with careful observation of serum iron and ferritin. PMID- 8498900 TI - Adverse events of subcutaneous recombinant human erythropoietin therapy: results of a controlled multicenter European study. AB - In a controlled European multicenter study, clinical tolerance of subcutaneously administered recombinant human erythropoietin (rh-EPO) therapy and its influence on the course of illness in 362 hemodialyzed patients (162 males, 200 females) from 16 European dialysis centers was studied. Of these, 181 patients served as a control group in the first year and received rh-EPO therapy in the second year. Of the 837 adverse events that occurred, 277 were classified as serious and 560 as nonserious. Thirty-two deaths have been reported for the study population: 18 in the control group and 14 in the therapy group. The individual analysis of the serious adverse events including death demonstrates a protective effect of rh-EPO on the high-risk cardiovascular situation of dialysis patients. Hypertension was no problem, and under rh-EPO therapy an increase in resistance to infection was observed. Subcutaneous rh-EPO treatment might have an even better safety profile than intravenous application. PMID- 8498901 TI - Some topics in bio-fluid mechanics. AB - Recently, several biomedical phenomena have been studied from the internal fluid dynamic point of view because their causes are attributed mostly to flow phenomena. The present paper reviews some current topics related to the unsteady flows, first in the large blood vessels and then in the lung, and shows how they are studied from the engineering point of view. PMID- 8498902 TI - Biochemical definition of the uremic syndrome and possible therapeutic implications. PMID- 8498903 TI - A new therapeutic approach to dialysis amyloidosis: intensive removal of beta 2 microglobulin with adsorbent column. AB - Amyloidosis, in which amyloid protein consists of beta 2-microglobulin (beta 2 M), is both a common and a serious complication of long-term hemodialysis. The mechanism of its development is not completely understood. Since beta 2-M is an amyloid protein, it is essential to try to remove as much of it as possible. A specific adsorbent of beta 2-M has been developed for use in direct hemoperfusion. The adsorbent is a porous cellulose bead to which hydrophobic organic compound is bound covalently. A combination of a high-flux membrane dialyzer and an adsorption column (BM-01) would make it possible to efficiently eliminate beta 2-M. Dialysis with a combination of direct hemoperfusion (DHP) and an adsorption column led to the elimination of more than 200-300 mg of beta 2-M. We observed 5 patients who received treatment with this column (BM-01) in combination with high-flux dialysis 3 times a week for periods of 1 week (3 patients), 6 months (1 patient), or 14 months (1 patient). It is demonstrated that the adsorbent column (BM-01) provides an intensive method to eliminate beta 2-M from the blood with no serious adverse effect. It thus has the potential to suppress the progression of dialysis amyloidosis. The use of this adsorbent column (BM-01) in combination with a high-flux dialyzer may present an improved approach to removing beta 2-M from the body. PMID- 8498904 TI - Focusing on membranes. PMID- 8498905 TI - Adequacy of dialytic therapy: Hydra complex and statistical concealment. PMID- 8498906 TI - Monitoring of the blood response in blood purification. AB - A principal objective of monitoring the blood response in procedures such as hemodialysis and cardiopulmonary bypass is to achieve an enhanced understanding of the relationship between blood component alterations and the biomaterials employed. The aim in a study of blood-biomaterial interactions of deriving a correlation between a characteristic of the biomaterial and a representative parameter of the blood response can be influenced in a clinical situation by antithrombotic agents, multimaterial contact, device utilization, blood condition, drug therapy, and the nature of the application. The selection of parameters representative of the blood response may require a compromise between the advantages of multiparameter assessment and the benefit of measuring a single parameter by a consistent methodology. Representative parameters are protein adsorption, platelet reactions, intrinsic coagulation and the contact activation phase, fibrinolysis, leukocyte alterations, and complement activation. Assessment during clinical application can be approached by consideration of blood response patterns. PMID- 8498907 TI - Future trends in renal replacement therapy. PMID- 8498909 TI - Abstracts from the 5th Annual Meeting of the International Society of Cardio Thoracic Surgeons. Kumamoto, Japan, July 22-24, 1992. PMID- 8498908 TI - Bionics in renal replacement therapy. PMID- 8498910 TI - The natural history of orthopaedic enthusiasms. PMID- 8498911 TI - The orthopaedic workforce in Queensland now and into the twenty-first century. AB - The objectives of this study were to determine the number and distribution of orthopaedic surgeons in Queensland at present and to assess the adequacy of trainee intake for the future. Characteristics of the orthopaedic workforce in Queensland in 1990 were analysed with regard to the total number of orthopaedic surgeons, their regional distribution, their ratio to the population and their age distribution. Similar statistics were derived for the years 1981 and 1986 and trends were examined. By projecting these trends, the number of surgeons likely to be practising in 2001 was estimated. Using projected population figures, the number of orthopaedic surgeons required in 2001 was calculated, assuming an optimum ratio of surgeons to population of one per 25,000. It was found that in 1990 sufficient orthopaedic surgeons were practising in Queensland but that there was some maldistribution. With the increased intake of five new training registrars per year, the number of orthopaedic surgeons in Queensland in 2001 should be appropriate, as long as current trends continue. PMID- 8498912 TI - Laparoscopic cholecystectomy and management of choledocholithiasis. AB - The advent of laparoscopic cholecystectomy (LC) has led to a reassessment of the approach to the management of choledocholithiasis. In a consecutive series of 418 patients undergoing LC, common bile duct (CBD) stones were suspected pre operatively in 130 patients. Forty-five of the patients (35%) were found to have CBD stones on either pre-operative endoscopic retrograde cholangiopancreatography (ERCP; 20) or on operative cholangiography (OC; 25). Common bile duct stones were detected on OC in a further 12 of 288 patients (4.2%) without pre-operative suspicion of choledocholithiasis. Of the total of 57 patients with CBD stones, the duct was cleared by pre-operative ERCP and endoscopic sphincterotomy (ES) in 15 patients. In 13 patients, two of whom had had a pre-operative ERCP and ES, duct clearance was achieved by relaxing the sphincter pharmacologically and flushing the CBD via the OC catheter. One patient had an on-table ERCP and ES with successful stone extraction during LC. Eleven patients were converted to open operation with bile duct exploration. Sixteen patients had a postoperative ERCP. In five patients the CBD stones had passed spontaneously in the time between LC and ERCP. Ten patients required ES to clear the duct of stones. One patient had a failed ERCP and is still awaiting a repeat. The remaining patient was scheduled, but did not return for follow-up ERCP. In summary, pre-operative ERCP was indicated in less than 10% of patients in this series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498913 TI - Thoracoscopy: a useful diagnostic and therapeutic procedure. AB - This study was performed to review the place of thoracoscopy in the diagnosis and treatment of intrathoracic disorders. A combined retrospective and prospective review was undertaken of the first 50 patients who underwent diagnostic or therapeutic thoracoscopy in Ballarat. Recurrent pleural effusions (29), pneumothoraces (7), or diffuse or localized lung disease (14) were the main indications. Thoracoscopy was performed in conjunction with pleural or lung biopsy, excision of cysts, or pleurodesis. Patient tolerance of the procedure was excellent with minimal postoperative pain. Operative morbidity rates were very low (< 4%). The low mortality rate was related to underlying disease processes. Hospital stay was short. The long-term results were excellent. Adequate tissue was obtained on biopsy in most cases, cure achieved for pneumothoraces, and permanent palliation after talc pleurodesis for malignant effusions approached 80%. PMID- 8498914 TI - Pneumogastrogram in the diagnosis of perforated peptic ulcer. AB - Early diagnosis and surgical intervention is important in the management of peptic ulcer perforation. This study looks at the value of a pneumogastrogram in the diagnosis of patients suspected of having a perforated peptic ulcer. One hundred and twenty-nine patients were studied. Pneumogastrogram increased the diagnostic yield of pneumoperitoneum from 66% following plain erect X-ray examination to 91%. The procedure was free of complications. PMID- 8498915 TI - Management of acute bleeding gastric malignancy. AB - Gastric malignancy was the cause of bleeding in 35 of a consecutive series of 2260 cases (1.5%) treated with upper gastrointestinal haemorrhage. Fifteen patients came to emergency surgery (43%). In 13 of 30 early endoscopies performed the lesion was thought to be benign (43%) and seven of these cases came to emergency surgery. Two patients died after 15 emergency operations (13%) compared with 15 deaths after 109 emergency operations (14%) for benign gastric ulcer during the same period of study. A total of four patients with malignant ulceration died after surgery in 33 cases (12%), two after 15 emergency operations and two after 18 elective procedures. The only significant predictors of urgent surgery for malignant ulcer were shock on admission and active bleeding or visible vessel on endoscopy. Resection of gastric malignancy was performed in 29 patients during initial admission and in four cases at a subsequent admission giving a final resection rate of 91%. Of the 28 patients with adenocarcinoma, 19 had localized disease (Stage I or II) (68%). Nine patients were treated by total gastrectomy, five at an initial elective procedure and four at a second procedure. PMID- 8498916 TI - Gastroduodenal tuberculosis. AB - Nine patients with gastroduodenal tuberculosis (GDTB) were seen over a period of 2 years at a tertiary level referral institute. Clinical presentation of GDTB is similar to that of peptic ulcer disease. Endoscopic biopsy and/or laparotomy and biopsy establish the diagnosis. Medical treatment is the mainstay of therapy, although surgical intervention may be required for the management of complications. Gastroduodenal tuberculosis should be suspected in patients, residing in areas where the disease is endemic, with a short history suggestive of peptic ulcer disease and an early onset of gastric outlet obstruction. PMID- 8498917 TI - Metastatic carcinoma in the neck: a clinical computerized tomography scan and ultrasound study. AB - Metastatic cervical lymph node involvement is a major determinant of treatment planning and prognosis of upper aerodigestive tract tumours. If the metastatic tumor invades the carotid artery wall then complete tumour excision is not possible unless carotid artery ligation or replacement is planned. A prospective study was performed to assess the role of palpation, computerized tomography (CT) and B-mode ultrasound scanning in the detection of metastatic cervical lymph node involvement in patients with upper aerodigestive tract tumours. In particular, detection of carotid artery wall invasion by tumour was examined. Thirty-two neck dissection specimens were available for histopathological confirmation of findings. Palpation under general anaesthesia was 87.5% sensitive and 87.5% specific in the detection of involved nodes. If a positive finding was defined as detection of a node greater than 15 mm in largest diameter, CT scanning was 78.6% sensitive and 93.8% specific, and the sensitivity of ultrasound was 81.3% and specificity was 84.6%. Ultrasound scanning was sensitive in excluding carotid artery wall invasion, identifying five out of five cases with one false positive and no false negative reports. The combination of palpation under general anaesthesia and B-mode ultrasound imaging provides a sensitive means of detecting the presence of metastatic cervical lymphadenopathy and invasion of the carotid artery wall. PMID- 8498918 TI - The role of computerized tomography in aorto-iliac vascular disease. AB - Computerized tomography (CT) now has a definite place in the assessment of aortic vascular disease. In a study of 96 patients with abdominal or thoracic aorto iliac problems, CT proved most useful in the management of haemodynamically stable patients with abdominal aortic aneurysms that were suspected of leaking. The complex anatomy associated with thoracic and abdominal aneurysms and aortic dissection was clearly defined. The interpretation of scans on postoperative aortic graft patients was difficult and less often helpful. The incidental finding of aortic disease during abdominal scans for a variety of other indications was infrequent and seldom contributed to patient management. The indications for CT have become far more selective. PMID- 8498919 TI - Laparoscopic assisted right hemicolectomy with Valtrac BAR (Biofragmentable Anastomotic Ring) ileotransverse anastomosis. AB - Laparoscopic techniques have been employed in a group of medically compromised patients requiring right hemicolectomy, permitting a shorter and lower placed abdominal incision than may have been expected with a conventional surgical approach. In eight patients requiring right hemicolectomy, full mobilization of the right colon from the caecum to the proximal transverse colon was performed laparoscopically. Resection and anastomosis then proceeded through a small right sided transverse abdominal incision. End to end ileotransverse anastomosis was performed in each instance employing the Valtrac BAR (Biofragmentable Anastomotic Ring) compressive anastomotic technique. The average operating time was 133 min. There was no mortality, but one patient developed pulmonary complications and three developed minor wound infections. An additional three patients developed urinary tract infections. There were no anastomotic complications. The average postoperative stay was 10 days. This study has indicated that laparoscopic techniques can be successfully applied to large bowel surgery, and may be of benefit to high risk patients. PMID- 8498920 TI - Results of a policy of selective immediate fistulotomy for primary anal abscess. AB - A prospective study of a policy of selective immediate fistulotomy in the management of acute primary anal abscesses was performed. Eighty-nine patients (74%) underwent simple drainage only, as no internal openings were found during drainage of pus (group A). Thirty-one patients (26%) had drainage of pus and immediate fistulotomy (group B). Follow up for groups A and B occurred at a median of 122 weeks (104-136 weeks) and 121 weeks (104-136 weeks), respectively. No patient in group A had residual problems with anal continence whilst two patients (6.5%) from group B had minor anal incontinence following the initial procedure (p = 0.07). Ten patients from group A (11%) and four patients from group B (13%) developed recurrent anal sepsis. The overall rate of recurrent sepsis was 11.7%. In those patients who had incision and drainage alone, 90% of those who developed a recurrence and 71% of those who did not develop a recurrence grew gut-associated organisms from pus obtained during the initial drainage of the acute abscess, giving a positive predictive value for recurrence of 13.8% for a culture of gut-associated organisms. The positive predictive value for recurrent sepsis for both groups taken together for a culture of gut associated organisms was 28.2%. Patients with acute primary anal abscess should be treated with simple drainage. PMID- 8498921 TI - An epithelial cyst of the suprasellar region. AB - A case of a 26 year old woman with increasing headaches due to a suprasellar cyst is described. Histology was consistent with an epithelial cyst with features resembling both Rathke's cleft cysts and enterogenous cysts. The differential diagnosis and treatment of suprasellar cysts is discussed. PMID- 8498922 TI - Hereditary non-polyposis colorectal cancer (Lynch syndrome I) in a 13 year old male. AB - A case of adenocarcinoma of the colon is reported. It presented in a family with hereditary non-polyposis colorectal cancer (HNPCC). Colonoscopic screening at a young age is recommended in such families. It also suggests a genetic basis for colorectal carcinogenesis in this family. Three of the members of this family also have peptic ulceration and an association between this syndrome and HNPCC is postulated. PMID- 8498923 TI - Hydatidemesis: a bizarre presentation of abdominal hydatidosis. AB - A 31 year old male presented with high grade fever and abdominal pain of 20 days duration. At the age of 9 he had been operated on for a solitary retroperitoneal hydatid cyst and had been asymptomatic until the age of 21 when he sustained a blunt injury to the abdomen. An exploratory laparotomy for splenic rupture revealed multiple intra-abdominal hydatid cysts, which were removed. The patient remained well until the present episode. An ultrasound examination revealed multiple intra-abdominal hydatid cysts. Seven days after admission, the patient developed hydatidemesis (hydatid cysts and membranes in the vomitus) and hydatidenteria (passage of hydatid membranes in the stools), and his pain and fever subsided. A Gastrografin study and a computerized tomography (CT) scan revealed hydatid cysts communicating with the stomach and duodenum. In view of his disseminated recurrent abdominal hydatidosis, he was treated with high dose, long-term albendazole along with regular follow up. This is the first documented case of disseminated abdominal hydatidosis presenting with a cystogastric fistula and hydatidemesis. PMID- 8498924 TI - Gastric, hepatic and small bowel infarction due to radiation aortitis in a 42 year old woman. PMID- 8498925 TI - Common bile duct obstruction due to intraluminal metastatic melanoma. AB - Although metastatic melanoma is renowned for its propensity to spread to a wide range of sites, symptomatic metastases within the biliary tree are very rare. A patient with a past history of melanoma who presented with obstructive jaundice and in whom computerized tomography (CT) scanning revealed a spherical filling defect 1 cm in diameter at the lower end of the common bile duct is reported. The obstructing lesion was thought likely to be a gallstone. However, on surgical exploration it was found to be a polypoid melanoma metastasis, freely mobile within the lumen of the lower duct but attached to its wall by a thin stalk. There was no evidence of metastatic melanoma elsewhere in the abdomen. The tumour was removed without difficulty, completely relieving the obstructive jaundice. The patient remains well 14 months later, with no evidence of recurrent visceral melanoma. PMID- 8498926 TI - Carcinoma of the thyroid gland and Gardner's syndrome. AB - A patient known to be suffering from Gardner's syndrome who developed carcinoma of the thyroid gland is presented. A review of the literature reveals that this relationship is not fortuitous and that it has the following characteristics: female predominance (89%), youth (< 30 years in 78%), papillary form (88%), multicentricity (70%) and thyroid carcinoma preceding diagnosis of hereditary polyposis in 30%. Hereditary polyposis patients affected by familial polyposis coli are at significant risk of developing extracolonic malignant tumours, and require life-long surveillance. Palpation of the thyroid gland and possibly ultrasound examination of the neck should be part of the routine follow up of these patients. PMID- 8498927 TI - Endometrial cancer: trends in incidence and survival: a preventable disease? AB - Endometrial cancer is the commonest gynaecological cancer. Its relative increase in incidence over recent decades has been generally associated with a reduction in mortality. Evidence is presented to show a considerable variation in incidence worldwide; Australia, like England and Wales, has a comparatively low incidence. The incidence is highest in parts of the United States where it has shown an annual fall of nearly 3% between 1973 and 1987. The influence of hysterectomy, oral contraception and hormone replacement therapy at the menopause are discussed relative to incidence and prevention of the disease. Obesity and its prevention are also shown to have an influence on incidence and its ethnic variation worldwide. Despite a minor improvement in survival in FIGO published figures, the recent COSA-UK-NZ 'high risk' trial highlights the importance to the patient of closely monitored clinical trials. PMID- 8498928 TI - An unusual vaginal foreign body. PMID- 8498929 TI - Vaginal delivery after caesarean section. PMID- 8498930 TI - Is there a lower limit for birth-weight/gestational age and antenatal steroid therapy. PMID- 8498931 TI - Hysterectomy in Australia. PMID- 8498932 TI - Breech presentation in South Australia, 1987-1989. AB - This study compares the maternal, obstetrical, labour and pregnancy outcome characteristics of 2,412 breech-presenting births with 17,946 vertex-presenting births. Mothers of babies presenting as breeches were significantly more likely to have had a previous miscarriage, an obstetric complication, a threatened miscarriage or threatened labour during the current pregnancy, or Caesarean section than mothers of babies with vertex presentation. The babies presenting as breeches had significantly more neonatal morbidity and perinatal mortality. They showed higher rates of suspected intrauterine growth retardation, prematurity, low birth-weight, low Apgar scores and congenital anomalies. The overall perinatal mortality for breech presentations was almost 9 times higher than for vertex presentations. Unconditional multiple logistic regression analysis showed that, even after adjusting for low birth-weight and the presence of congenital anomalies, breech presentation still showed a statistically significant association with perinatal death. The study alludes to the possibility that breech presentation, in a significant number of cases, may not be coincidental but a marker for some preconceptional or prenatal disturbance. The study also shows an excess of breech presentations in females which is unexplained and may point to a genetic or hormonal susceptibility of the fetus. PMID- 8498933 TI - Placenta praevia: does uterine activity cause bleeding? AB - Twenty-two women > 24 weeks' gestation with a central placenta praevia were monitored to determine if an increase in uterine activity precedes bleeding in patients with central praevias. Monitoring of all subjects began at 26.3 +/- 4.4 weeks and continued until 37 weeks (or delivery if preterm). All subjects had at least one haemorrhage, 7 women had 2, and 4 subjects had 3 episodes of bleeding. Only 3 patients delivered at term while the remainder (86%) delivered preterm. The gestational age at first episode of bleeding was 29.1 +/- 3.6 weeks and at delivery was 34.3 +/- 3.3 weeks. Nine women (41%) had an increase in uterine activity above baseline the day or the day preceding the first haemorrhage. The increase in uterine activity was not statistically significant when compared to the 6 days prior to bleeding when all 22 patients were considered. PMID- 8498934 TI - The significance of recurrent polyhydramnios. AB - A study of 30 women who had polyhydramnios in more than 1 pregnancy revealed that 8 of the 36 resultant pregnancies (22.2%) were associated with diabetes mellitus, 14 (37.8%) with fetal macrosomia, and the perinatal mortality was 16.2% (6 of 37). The incidence of major fetal malformations or abnormalities was 18.9% (7 of 37); 4 of the 6 deaths resulted from malformations (anencephalus (2), hydrocephalus (1), nonimmune hydrops (1)), and the other 2 deaths were from hyaline membrane disease associated with prematurity. Recurrent polyhydramnios occurred in 1 in 1,720 pregnancies. The onset was acute in 3, subacute in 2 and chronic in 31, the perinatal deaths in these categories being 2, 1 and 3 respectively. The risk of recurrent polyhydramnios is the risk of fetal malformation and premature delivery. The latter may be preventable by prompt therapy with indomethacin, and serial amniocentesis if this therapy fails. PMID- 8498935 TI - Induction of labour in pregnancy complicated by cardiac disease. AB - Twenty one pregnant patients with cardiac disease had induction of labour for various obstetric reasons with a modified oxytocin infusion method. All of them went into labour and delivered within 20 hours. Twenty patients delivered vaginally. Three neonates had birth asphyxia (Apgar score < 7) and 1 of them died on the 4th day from prematurity. No adverse effect of oxytocin infusion on maternal cardiac status was observed and all of the women went home in good condition. Induction of labour with a modified oxytocin infusion is a safe and effective alternative for selected gravidas with cardiac disease where elective delivery is warranted. PMID- 8498936 TI - ECG waveform analysis in intrapartum fetal monitoring. AB - Intrapartum cardiotocography (CTG) has a high false positive rate and, in the absence of facilities for fetal scalp blood sampling, is associated with increased operative deliveries for 'fetal distress'. It is presently possible to obtain a representative fetal ECG signal using the fetal scalp electrode. There is renewed interest in fetal ECG waveform analysis in the hope that it will improve the specificity of detecting intrapartum fetal hypoxia when there is an abnormal fetal heart rate pattern. Two portions of the fetal ECG are potentially useful: the ST waveform (T/QRS ratio) and the PR interval correlated with the RR interval. Animal experiments suggest that changes in the ST waveform, increase in the T wave amplitude in particular, reflect myocardial anaerobic metabolism. Clinical studies have shown poor correlation between the T wave changes and fetal heart rate changes. There is also concern that the sensitivity of the ST waveform changes for fetal acidaemia may be poor. More information is required before its use is incorporated into routine clinical practice. PMID- 8498937 TI - Pregnancy hazards associated with low maternal body mass indices. AB - Analysis of the obstetric records of 41,955 public patients with singleton pregnancies at the Mater Misericordiae Mothers' Hospital, South Brisbane, showed a significant association (increased odds ratio) between Low Maximum Pregnancy Maternal Body Mass Index (Quetelets Index 20-24.6 and maternal anaemia, the use of intravenous tocolysis, low birth-weight (< 1,500 g and < 2,500 g), low Apgar score (< 7 at 5 minutes) and perinatal mortality. Parturients with a Very Low Body Mass Index (Quetelets Index < 20) had even greater odds ratios in respect of the above obstetric hazards. Both the Low and Very Low Body Mass Index cohorts had significantly reduced risks of having hypertension (both essential and preeclamptic) or having their labours induced or augmented. The results are presented as odds ratios with confidence limits after controlling for the potentially confounding covariables of maternal age, parity, smoking habits and gestational age. PMID- 8498938 TI - Measurement of blood pressure during pregnancy: evaluation of the 'TriCUFF'. AB - Previous surveys have revealed that a major source of error in measuring blood pressure in pregnant women is failure to use a large cuff when necessary. We have tested the hypothesis that this problem could be overcome by using a single cuff containing automatically selected inflation bladders of appropriate size, the TriCUFF. We compared readings obtained with the TriCUFF with those obtained using standard adult or large (obese) cuffs in 51 pregnant women. Thirty nine had normal upper arm circumferences (< 34 cm) and 12 increased arm circumferences (> or = 34 cm). The TriCUFF overestimated standard cuff systolic and diastolic (phase IV) readings by 2 (0-4) mmHg (mean, 95% confidence limits) (p < 0.05). There was no difference between readings for women with large arms. Agreement between readings by both methods was acceptable for clinical practice in most cases. Use of the TriCUFF could significantly improve the accuracy of blood pressure recording in pregnant women. PMID- 8498939 TI - A controlled trial of amnioinfusion: the prevention of meconium aspiration in labour. AB - The purpose of this study was to examine the effect of amnioinfusion on the incidence of meconium aspiration syndrome, perinatal asphyxia and obstetrical intervention rate amongst patients with moderate and thick meconium-stained liquor. A total of 112 patients were studied in a prospective fashion; 60 received amnioinfusion and 52 served as controls. We have shown that amnioinfusion is a simple, relatively inexpensive and safe procedure. It benefits the patient in terms of reduction in the likelihood of operative intervention (specifically Caesarean section) for fetal distress and improvement in neonatal outcome with reduced frequency of neonatal acidaemia. PMID- 8498940 TI - Chlamydia trachomatis infections in female tertiary students. AB - Chlamydial infection of the endocervix was identified in 19.8% of 258 University students undergoing pelvic examination in a Student Services Health Clinic. The majority of consultations were for routine Papanicolaou smear. Chlamydial infection was present in 50% (12 of 24) of the women who had clinical evidence of mucopurulent cervicitis. PMID- 8498941 TI - Postoperative vomiting factors in IVF patients. AB - Postoperative vomiting patterns were documented in 504 patients having general anaesthesia for oocyte retrieval for in vitro fertilization or related procedures and compared with patient preoperative history and expectations, response to ovarian hyperstimulation, and details of the anaesthesia. The results showed that the likelihood of vomiting was related to peak plasma oestradiol level and the patient's expectation based on previous experience of anaesthesia. PMID- 8498942 TI - Side-effects and complications of outpatient hysteroscopy. AB - Outpatient hysteroscopy and biopsy was performed on 403 occasions. Complications were rare (< 1%). Side-effects occurred in 70% of patients but rarely required treatment. Preoperative explanation of the type, severity and frequency of side effects reduces patient anxiety at the time when side-effects occur. PMID- 8498943 TI - Submucous fibroids: clinical profile and hysteroscopic management. AB - Fifty submucous fibroids were removed by hysteroscopic resection from 37 patients with abnormal uterine bleeding. Thirty-seven fibroids were completely resected and 13 incompletely resected. Nine patients also had rollerball endometrial ablations. The average follow-up period was 14 months (4 to 51 months) in 33 patients available for follow-up. All of these patients had cure of their symptoms, 3 after repeat operations. The 1 immediate complication was a postoperative infection. A normal uterine cavity was found in 13 of 14 patients examined by office hysteroscopy at follow-up. PMID- 8498944 TI - Laparoscopic culdotomy. AB - Laparoscopic culdotomy has been performed in 32 patients. The indications for the procedure included the removal of organs or tissue excised by operative laparoscopy, excision of vaginal endometriosis involving the pouch of Douglas and drainage of a pelvic haematoma. The surgical technique is described and no complications resulted from this technique. Laparoscopic culdotomy has advantages for the removal of lumps exceeding 1 cm, and for the drainage of a pelvic haematoma or pelvic abscess. It is also an integral step in the removal of infiltrating endometriotic lesions in the pouch of Douglas which are attached to the vagina. PMID- 8498945 TI - The residual adnexa syndrome. AB - The clinical profile of a group of 208 women who presented with residual adnexal disease subsequent to hysterectomy was studied retrospectively; 121 patients had the uterus removed vaginally and 87 per abdomen. The majority of the patients had the hysterectomy at less than 40 years of age, with a mean and median age of 33 years, and more than 60% presented with adnexal symptoms and signs within 5 years of hysterectomy. A detailed analysis of the symptoms and signs and pathology of the removed uterus in both groups was similar although as expected there was an associated finding of prolapse in a significant number of those treated by vaginal hysterectomy. There were significant delays both in the definitive diagnosis of subsequent residual adnexal disease and definitive treatment. The pathological changes in the removed residual adnexa were varied, but with a high incidence of inflammatory changes involving both the tube and ovary. This was particularly evident in those patients in whom the uterus had been removed by the vaginal route, suggesting that this may be related to the usual fixation or approximation of the conserved tube to the vaginal vault at the time of vaginal hysterectomy. PMID- 8498946 TI - The efficacy of the pipelle endometrial biopsy in detecting endometrial carcinoma. AB - The purpose of this study was to determine the efficacy rate of the Pipelle endometrial biopsy sampler (Pipelle de Cornier) (1) in detecting endometrial carcinoma, and to analyze the tumour variables that may influence the success rate. Thirty seven women with known endometrial carcinoma were tested preoperatively; there were 25 correct diagnoses (67%), the remaining 12 cases (33%) failed to demonstrate the correct diagnosis: 4 showed 'atypical epithelium', 2 showed 'atypical hyperplasia', 3 showed 'nonspecific epithelium' and the remaining 3 showed 'necrotic hyalinized material'. All cases were analyzed with respect to several tumour parameters, including the degree of differentiation, tumour volume, depth of invasion, and the extent to which the tumour filled the endometrial cavity. Poor results were obtained in well differentiated, low volume, and minimally invasive tumours, i.e. most early tumours, precluding its use as a screening tool. A positive biopsy can save patients the time, cost, and inconvenience of a dilatation and curettage. However, in the light of these findings, a nonspecific finding should be interpreted with caution. PMID- 8498947 TI - Menstrual blood loss measurement with gynaeseal. AB - The diagnosis of menorrhagia is usually based on the subjective complaint of heavy menstrual bleeding, although up to 50% of women describing menorrhagia have measured menstrual loss within normal limits. Treatment is usually started without first establishing an objective diagnosis, because menstrual blood loss measurement is not widely available to clinicians. Current laboratory methods of measuring menstrual loss involve extraction of menses from sanitary wear. Many women find collection of sanitary wear unacceptable and laboratory staff find the menstrual extraction procedure unpleasant and time-consuming. We investigated the use of Gynaeseal, a vaginally placed latex menstrual seal, in women with normal menstrual loss (n = 10) and menorrhagia (n = 12) with regard to its suitability for the measurement of menstrual loss and efficacy as alternative sanitary protection. Twenty-one of the 22 women found the device easy to insert, but 16 found it messy to remove. All of the 6 couples having coitus found the device caused no discomfort. All women with menorrhagia and 4 of 12 women with normal menstrual losses were dissatisfied with the menstrual seal provided by gynaeseal. Gynaeseal does not contain menstrual blood efficiently in women with menorrhagia and is therefore unsuitable for the measurement of menstrual blood loss. PMID- 8498948 TI - Family planning practices among Lebanese, Turkish and Vietnamese women in Sydney. AB - This paper is based on some of the data collected in a fertility and family planning survey conducted in 1988 among a probability sample of 980 married immigrant women in Sydney. The sample consisted of 507 Lebanese, 250 Turkish and 223 Vietnamese women. This study has revealed differences within and between the 3 migrant groups and the general population. Fertility among the 3 groups, but particularly among the Lebanese, was relatively high. While most women understood about birth control, there was a heavy reliance on traditional methods. Incidence of sterilization and hysterectomy was low compared to the general population. Use of abortions as a method of birth control was quite common among the Turkish women. Most women relied on their doctors for contraceptive advice and there was little knowledge and even less use of family planning and women's health centres. The study revealed an unmet need for culturally sensitive family planning information and services to these women. PMID- 8498949 TI - A prospective randomized study comparing the clinical effects of a norethisterone and a levonorgestrel containing low dose oestrogen oral contraceptive pills. AB - The two types of low dose oral contraceptives one containing levonorgestrel the other containing norethisterone have been compared in a randomized prospective study. We have found that cycle control was much poorer with the norethisterone pill and would therefore recommend that if the norethisterone-containing pill needs to be prescribed then either the 1 mg or the 'synphasic' preparation should be considered. PMID- 8498950 TI - Management dilemmas with major placental abruptions in the midtrimester. PMID- 8498951 TI - A case of spontaneous resolution of nonimmune hydrops fetalis. AB - Spontaneous intrauterine resolution of severe nonimmune hydrops fetalis has been rarely reported in the literature. A case of severe fetal hemolytic anaemia with hydrops fetalis but subsequent spontaneous resolution is reported along with a discussion of possible aetiologies. PMID- 8498952 TI - Active chronic peptic ulcer disease complicated by gastric outlet obstruction in pregnancy. AB - A case of active peptic ulcer disease in a primigravida at 29 weeks' gestation is presented, with a literature review. This particular case was complicated by gastric outlet obstruction, a complication which has not been previously reported in the obstetric literature. Although an uncommon diagnosis in pregnancy, the investigations for peptic ulcer disease should be actively pursued. Treatment can prevent serious complications. PMID- 8498953 TI - Spinal cord injury after forceps rotation: the role of glioneuronal heterotopias. PMID- 8498954 TI - Catamenial epilepsy. PMID- 8498955 TI - Ectopic pregnancy contralateral to unilateral GIFT. PMID- 8498956 TI - Pelvic actinomycosis in association with an intrauterine device. AB - A case of pelvic actinomycosis is described which occurred in association with the use of an intrauterine device (IUD). Initially medical management alone was used, but surgical intervention was necessitated for multiple pelvic abscesses. We would strongly recommend that any IUD be removed should it be associated with actinomyces on genital smears and/or culture. If sepsis is also apparent, IUD removal with use of long-term antibiotics is required. PMID- 8498957 TI - Leiomyoma of the female urethra. PMID- 8498958 TI - [Genetic engineering of human insulin. II. Exclusion HPLC of biotechnological precursors. Factors affecting resolution and selectivity]. AB - Mechanisms of the exclusion-sorption interaction of insulin-containing proteins with the column support in accordance with the chemical and three-dimensional structure were considered. The weak adsorption of the linear proinsulin and fusion protein in non-denaturing conditions, and dynamics of the SDS-protein complex's formation in denaturing conditions were studied. The obtained results are used for SE HPLC analysis of the main products and intermediates at essentially all steps of the recombinant human insulin production. PMID- 8498959 TI - [Synthesis of a partially purified fragment of salmon calcitonin 1-16 using a phenylhydrazide protective group]. AB - The partially protected fragment Boc-Cys(Acm)-Ser(Bu(t))-Asn-Leu-Ser(Bu(t))-Thr (Bu(t))-Cys(Acm)-Val-Leu-Gly-Lys(Boc)-Leu-Ser(Bu(t))-Gln-Glu(OBu(t ))- Leu-OH of salmon calcitonin was synthesized by the segment condensation in solution. Segments were synthesized by the DCC/HOBt method in solution with phenylhydrazide as a semipermanent protecting group for the carboxyl function of the C-terminal residue. The phenylhydrazide group was removed by oxidation with air oxygen catalyzed by copper pyridine complexes under mild conditions. The segments were then condensed by the DCC/HOBt method according to the scheme (6 + 3) + (3 + 4). The proposed scheme makes it possible to product the partially protected fragment 1-16 of salmon calcitonin on the gram scale. PMID- 8498960 TI - [Synthesis of lipophilic and fluorescent derivatives of N-acetylmuramoyl-L-alanyl D-isoglutamine]. AB - Synthesis of lipophilic derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) by condensation of the C-terminal amino acid moiety in MDP molecule with phosphatidylethanolamine was carried out. Fluorescent lipophilic derivatives of MDP were synthesized by condensation of MDP with phosphatidylethanolamines labelled in the hydrophobic moiety, e.g. 1-acyl-2-[9(10)-(4-pyrenyl)stearoyl]-sn glycero-3-phosphoethanolamine and pyrenylphosphatidylethanolamine. PMID- 8498961 TI - [Biopolymer fragments, containing glycosylphosphate residues. 12. Synthesis of glycosylphosphosugars, containing 2-acetamido-2-deoxy-alpha-D mannopyranosylphosphate residues including a fragment of the Neisseria meningitidis A capsule antigen]. AB - 2-Acetamido-3,4,6-tri-O-benzoyl-2-deoxy-alpha-D-mannopyranosyl hydrogen phosphonate was synthesised and used for the first syntheses of glycosyl phosphosugars containing N-acetylmannosamine residue. The phosphodiesters prepared include ManNAc(alpha)-P-6Man(alpha)Me, an analogue of the fragment of some lysosomal glycoproteins, and ManNAc(alpha)-P-6ManNAc(alpha)Np, a derivative of the fragment of the capsular antigen from Neisseria meningitidis A. PMID- 8498962 TI - [Study of the interaction of alpha-tocopherol with phospholipids, fatty acids, and their oxygenated derivatives by (31)P-NMR spectroscopy]. AB - Interaction of alpha-tocopherol with phospholipids, oleic, ricinoleic acids and linoleic acid hydroperoxides was investigated by means of 31P NMR spectroscopy on a model artificial membranes containing egg phosphatidylcholine and lysophosphatidylcholine. alpha-Tocopherol was shown to support the bilayer organization of lysophospholipids, whereas its introduction into the lecithin water system stimulated the hexagonal phase formation. Free fatty acids exhibited a synergism to alpha-tocopherol, the effect of the hexagonal phase formation being at most increased by oxygenated acids--ricinoleic acid and linoleic acid hydroperoxides. In accordance with the experimental data, a conclusion about modifying and structuring action of alpha-tocopherol was made. Origin of the alpha-tocopherol's modulating effect on the membrane structure and a possible role of hexagonal phase forming upon its action in the course of peroxidation of lipids was discussed. PMID- 8498963 TI - The renin-angiotensin paradigm. Practical therapeutical consequences of basic research. AB - The challenge in hypertension research is the elucidation of the primary, genetic causes of elevated blood pressure. The basic information on how a cell, an organ, and the whole body function resides within the chromosomes, the individual genes and their DNA sequence. The problem with understanding primary (genetic) hypertension in man is that several genes are involved in the cardiovascular control mechanisms and that the genetics are complex. In addition, environmental factors which act over long time-spans confound the genotype/phenotype relationship individually, within a family, and regionally. This shows that while monogenetic, dominant traits and diseases such as some lipid disorders may be studied with relative ease, polygenetic diseases like primary hypertension remain puzzles, which make well defined experimental models as well as new strategies in the genetics of human primary hypertension mandatory. The availability of new molecular biological techniques enables us to conduct genetic linkage studies in humans and in animal models on a more extensive basis. Using gene technology it is possible to introduce new, additional genes in normotensive and hypertensive animals. It is also possible, in the mouse, to delete or mutate specific genes, and similar technology is being developed for use in the rat. This marks the important transition from classic breeding, the experiments of nature, to "high tech" genetics with previously impossible and unparalleled opportunities and the use of this in formation and methodology for clinical medicine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498964 TI - Tissue renin: focus on vascular angiotensin formation. AB - Local vascular formation of angiotensin (Ang) peptides was investigated in isolated, plasma-free perfused rat hindquarters. Analysis of perfusate by high performance liquid chromatography and radioimmunoassay demonstrated spontaneous releases of Ang I and II from hindlimb vasculature. Captopril suppressed Ang II and increased Ang I levels. Formation of Ang peptides was abolished by bilateral nephrectomy but unaltered by subtotal 5/6 nephrectomy. Infused renin was taken up by hindlimb vasculature and led to substantial increases of local Ang formation and perfusion pressure. Both effects were sensitive to captopril (CAS 62571-86-2) and to the renin inhibitor H-142 (H-Pro-His-Pro-Phe-His-Leu-Val-Ile-His-OH). Conversion of Ang I to Ang II in hindquarter vasculature was approximately 75% and completely suppressed by captopril. Evidence for and against local vascular synthesis of renin is briefly discussed. In conclusion, the data indicate substantial local vascular formation of Ang I and II which, however, appears to be mainly due to plasma-derived renin. PMID- 8498965 TI - The cardiac renin-angiotensin system. From basic research to clinical relevance. AB - Local, tissue-resident renin-angiotensin systems are increasingly being recognized as important neurohumoral regulatory units which may act independently of the circulating system. Here, the evidence supporting the existence, functional integration, and physio-pathological role of the cardiac renin angiotensin system is reviewed. The elements of the catalytic cascade of the system, renin, angiotensinogen, angiotensin-converting enzyme, and the specific angiotensin receptor have all been identified in cardiac tissues as synthesized there by local expression of the respective genes. Modulation of gene expression in response to various perturbations has been demonstrated, and may be regulated independently of the plasma or other tissue renin-angiotensin systems. In isolated hearts, generation of the biologically active peptides, angiotensin I and II, has been documented, establishing the capability of this system to act as a functionally integrated catalytic pathway for the production of angiotensin II. Through its specific receptors angiotensin mediates profound effects on cardiomyocyte function and, as we are beginning to learn, on structure and growth. The remarkable therapeutic potential of drugs that inhibit the renin angiotensin system in a number of cardiovascular disorders emphasizes the likely role that the cardiac RAS plays in health and disease. Continued efforts at elucidating the precise nature of this role will not only enhance our understanding of this system, but also translate into further clinical progress. PMID- 8498966 TI - The renin-angiotensin system in the brain. Localization and functional significance. AB - Many neuropeptides have been localized in brain areas involved in cardiovascular regulation. In some cases, regulatory systems which have been originally described in other organs have been found in the brain. A prominent member of this group is the renin-angiotensin system. All of its known components have been localized in the central nervous system and angiotensin II has numerous actions in the central regulation of cardiovascular homeostasis. In addition there are actions which go beyond an active role in the control of blood pressure; these include behavioural actions and the regulation of thirst. The brain renin angiotensin system interacts with other neurotransmitters such as the catecholaminergic system and may act as a neuromodulator. PMID- 8498967 TI - Localization of components of the renin-angiotensin system and site of action of inhibitors. AB - The renin-angiotensin system plays an important role in the regulation of blood pressure and fluid and electrolyte homeostasis. Components of this system, renin, angiotensin converting enzyme (ACE) angiotensinogen, angiotensin II and angiotensin II receptors have been found in many tissues including kidney, adrenal, blood vessels and in discrete brain regions. This suggests that in addition to circulating angiotensin II, endogenous tissue renin-angiotensin system may also be important in cardiovascular control and maintaining fluid balance. Inhibitors for ACE are used successfully in the treatment of hypertension and chronic heart failure. In experimental animals, these inhibitors are found to block ACE in the kidney, lung, adrenal, blood vessels and the forebrain circumventricular organs after oral administration. The time course of tissue ACE inhibition correlated closely with the blood pressure lowering effect of these drugs. Most ACE inhibitors are unable to penetrate the blood-brain and blood-testis barriers. However, the more lipophilic drugs do penetrate the blood brain barrier, especially after chronic administration. The potential use of inhibitors for renin and angiotensin II receptors for the treatment of hypertension are being explored. An inhibitor for the AT1 angiotensin receptor, losartan (CAS 124750-99-8), which has potent antihypertensive effect, demonstrated dose and time dependent inhibition of AT1 receptors in the kidney and adrenal. Losartan also crossed the blood-brain barrier after acute peripheral administration suggesting additional possible central sites of action. PMID- 8498968 TI - Dependence of angiotensin production in transgenic mice carrying either the human renin or human angiotensinogen genes on species-specific kinetics of the renin angiotensin system. AB - In order to study the functional role of the renin-angiotensin system in the control of blood pressure, projects were initiated using transgenic mice carrying either the human renin gene or the human angiotensinogen gene. To extend the usefulness of the transgenic model system of hypertension research, a two-tiered strategy for generation of transgenic mice with high blood pressure has been developed. This unique system allows the establishment of transgenic lines with a strict species specificity of the renin-angiotensinogen reaction exhibited by transgene products that are regulated in a tissue specific manner. In this report, the strategy concerning the "two-tiered method" is presented and evidence is provided the overproduction of angiotensin occurs only in the combined reaction with human renin and human angiotensinogen expressed in transgenic mice. PMID- 8498969 TI - Angiotensin II receptors: cloning and regulation. AB - Angiotensin II subtype 1 (AT1) receptor cDNA was cloned by expression cloning from bovine adrenal cortical cells. Human AT1 receptor was also cloned. These receptors were found to have a seven transmembrane structure. The receptor seems to interact with more than one type of G-proteins. AT1 consists of subtypes. cDNA for AT1A was cloned from rat kidney and that for AT1B was cloned from rat adrenal by plaque hybridization. They have similar base sequences in the coding region but are different in non-coding regions. Their functional implication is not clear. The regulation of the receptors occur at many stages. Expression of mRNA is studied in cultured rat mesangial cells. It was down regulated by angiotensin II and cAMP. On the other hand in whole body experiments, chronic infusion of angiotensin II was shown to upregulate adrenal AT1, and bilateral nephrectomy or losartan (CAS 124750-99-8) administration reduced AT1 mRNA expression. In addition to AT1 and AT2 the presence of a new subtype AT3 has been shown. PMID- 8498970 TI - Prostaglandin-mediated actions of the renin-angiotensin system. AB - The adequate biological function of the renin-angiotensin system in blood pressure regulation and volume control involves additional factors for a fully balanced response. This includes arachidonic acid-derived lipid mediators, the eicosanoids. Angiotensin II (Ang II) causes (AT1)-receptor mediated stimulation of phospholipase C, resulting in generation of IP3 (inositol triphosphate) and activation of protein kinase C, elevated cytosolic Ca+ and stimulation phospholipase A2. These processes culminate in the generation of cell-specific eicosanoids and their autocrine action on the generating cell or paracrine effects on cells in the vicinity. In vascular tissue, liberated arachidonic acid is mainly converted into vasodilator prostaglandins, i.e. prostacyclin (PGI2) and PGE2. These prostaglandins may attenuate any direct Ang II-induced vasoconstriction, lower systemic vascular resistance and stimulate renal sodium excretion. In some vessels, arachidonic acid released by Ang II may also be converted to vasoconstrictor eicosanoids, i.e. thromboxane A2, PGF2 alpha and 12 HETE. The biological significance of endogenous eicosanoid generation becomes evident if vasoactive eicosanoids become limiting factors for maintaining homoiostasis, i.e. in the fetal circulation, Bartter's syndrome and congestive heart failure where vasodilating eicosanoids (PGE2, PGI2) are involved in maintenance of low vascular resistance and reduced or absent vasoconstriction by Ang II. Vasoconstrictor eicosanoids (thromboxane A2, PGF2 alpha, 12-HETE) contribute to high blood pressure in (renovascular) hypertension and pregnancy induced hypertension. Alternatively, generation of vasodilator prostaglandins may be reduced in these situations. The vascular renin-angiotensin system is subject to the action of a number of drugs and chemicals, most notably specific inhibitors of the angiotensin-converging enzyme and drugs affecting kidney function (furosemide) and/or vessel tone (propranolol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498971 TI - Angiotensin II receptor antagonists. AB - The development of novel non-peptide compounds with high affinity for-angiotensin II (Ang II) receptors has greatly facilitated the subclassification of Ang II receptors into AT1- and AT2-receptor subtypes. Whereas PD 123177 (1-(4-amino-3 methylphenyl)methyl-5-diphenyl-acetyl-4,5,6,7-tetrahydro- 1H-imidazol [4,5 c]pyridine-6-carboxylic acid) is the prototypical antagonist for AT2-receptors, DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1 H-tetrazol-5-yl)biphenyl-4 yl) methyl) imidazole, losartan) is the prototypical antagonist for AT1 receptors. So far, non-selective non-peptide Ang II receptor antagonists have not been identified although AT1/AT2 selectivity ratios of 17 and 37 have already been reported for BIBS 39 (4'-[(2-n-butyl-6- cyclohexylaminocarbonylamino benzimidazole-1-yl)-methyl] biphenyl-2-carboxylic acid) and BIBS 222 (2-n-butyl-1 [4-(6-carboxy-2, 5-dichlorobenzoylamino)-benzyl]-6-N-(methylaminocarbonyl)- n pentylaminobenzimidazole). Functional studies with AT1-antagonists indicate that Ang II antagonism at the receptor level can be rather complex. Experimental data suggests that not only are receptor binding kinetics involved, but also that additional binding sites, and possibly even AT1 subtypes, are involved. The antihypertensive activity of the AT1-antagonist DuP 753 is demonstrated in a high renin (2K 1C) and a low renin (TGRmREN2) hypertensive rat model. The kidney especially is very sensitive to Ang II and this organ seems to be a target for Ang II receptor antagonists. This can be demonstrated with experiments on the isolated rat kidney. PMID- 8498972 TI - The renin system and new understanding of the complications of hypertension and their treatment. AB - The renin-angiotensin-aldosterone hormonal axis is the major long-term servocontrol for regulation of both arterial blood pressure and sodium balance. It supports normotension or hypertension via angiotensin vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. Normally, in the presence of hypertension or sodium-volume excess, plasma renin activity promptly falls to zero. Accordingly, any renal secretion of renin in the face of high blood pressure is abnormal. In established essential hypertension varying degrees of abnormal plasma renin activity operate to cause or sustain the hypertension; only very low plasma renin values reflect a normal renal response. Human hypertensive disorders comprise a spectrum of abnormal plasma renin-sodium volume products. High renin, intensely vasoconstricted, hypovolemic forms (e.g., malignant, renovascular) are one extreme of the spectrum; "wet"-volume-excess low renin forms are the other extreme (e.g., primary aldosteronism, low-renin essential hypertension). These varying, but abnormal renin-sodium products are caused by a renal lesion in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium despite systemic hypertension and sodium excess. Thus, hypertensive patients cannot suppress their renin secretion normally. The hypertension from this renal lesion is correctable by agents that reduce renin secretion or block its effect (beta blockade, CEI, renin inhibition, or angiotensin II antagonism). None of these agents lower blood pressure after binephrectomy, verifying the renal origin of renin in the cardiovascular control system. In essential hypertension, the plasma renin level appears as a continuous variable associated with greater risk of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498973 TI - Acute effects of a pseudo-tetrapeptide as renin inhibitor on blood pressure and renin-angiotensin system of sodium-repleted and sodium-depleted hypertensive patients. AB - The blood pressure and renin-angiotensin system effects of the new renin inhibitor, SR 43845 ([N-(pyridyl-3-propionyl)-phenylalanyl- histidyl-(3S,4S) ACHPA-isoleucylamino]-2-methyl-2-dihydroxy-1,3-propane), were studied in 12 hypertensive patients on a normal sodium intake who received a 30-min infusion of intravenous SR 43845 at one of 3 doses: 30, 100 or 300 micrograms/kg (4 patients per group). Eight further patients were infused with the 300 micrograms/kg dose 24 h after 80 mg furosemide orally. In sodium-repleted patients, the 30, 100 and 300 micrograms/kg doses induced a rapid fall in diastolic blood pressure (DBP) which culminated at 4.5, 7.5 and 3.9 mmHg, respectively. Salt depletion increased the renin inhibitor-induced fall in DBP to 10.8 mmHg. DBP was back to baseline at 60 min after starting the lowest dose and 180 min after starting the highest dose. Heart rate did not change. In four of the sodium-depleted patients, 50 mg captopril was given orally at T = 180 min, when blood pressure had returned to baseline. The decrease in BP (8.8 mmHg) was similar to that initially obtained with the renin inhibitor (10.1 mmHg). Plasma angiotensin (Ang) I was dose dependently reduced by 62, 93 and 92% of baseline values 10 min after the start of the infusion in sodium-repleted patients, and by 90% in sodium-depleted patients; it returned to baseline in both situations between 180 and 360 min. Plasma Ang II levels changed in parallel with those of plasma Ang I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498974 TI - Discovery of remikiren as the first orally active renin inhibitor. AB - Angiotensin converting enzyme (ACE) inhibitors are used for the treatment of hypertension and congestive heart failure. However, ACE not only cleaves angiotensin I but is also responsible for the degradation of bradykinin. Therefore, renin inhibitors which block the system at an early step without influence on bradykinin should be devoid of side effects. Since renin has a very strong species specificity, it was necessary to develop new techniques to measure arterial pressure as well as hypertension models in primates in order to select orally active renin inhibitors. Remikiren (Ro 42-5892, CAS 126371-83-3) is a very potent renin inhibitor in vitro (IC50 for human renin = 0.7 nmol/l) and in vivo. Despite short lasting biochemical changes the arterial blood pressure decrease induced by remikiren is very long lasting (over 24 h). Several in vivo experiments have shown that remikiren is specific for renin and does not decrease arterial pressure by an unrelated mechanism. In sodium depleted monkeys, the blood pressure decrease induced by remikiren was similar to the blood pressure decrease induced by cilazapril, an ACE inhibitor. Clinical results seem to confirm the preclinical findings and show that remikiren is indeed a potent orally active renin inhibitor inducing a long lasting blood pressure decrease. PMID- 8498975 TI - Inhibitors of the renin-angiotensin system. Clinical pharmacology studies on kinetics, dynamics and concentration-effect relationships. AB - Drug induced modification of the renin-angiotensin system is of established benefit in the treatment of hypertension and heart failure. The responses to the angiotensin converting enzyme (ACE) inhibitor enalapril (CAS 75847-73-3) have been studied in essential hypertension and normotensive controls. The kinetics and dynamics of enalapril have been characterised in an integrated concentration effect model to identify factors underlying responsiveness to the ACE inhibitor. In addition models to predict the response to long-term treatment from changes after the first dose have been developed. Enalapril response could be described by a non linear (Emax) model defined by two parameters - the maximum response (Emax) and the drug concentration required to cause 50% of the maximum response (C50). Acute dosing accurately predicted the Emax after 6 weeks treatment. In addition to individual pharmacokinetics, pretreatment blood pressure was the most important determinant of response to enalapril. In caucasian salt-replete essential hypertension neither age nor plasma renin activity were major factors. However, in states of sodium restriction and/or diuretic treatment, the response to enalapril was greatly increased. The angiotensin II receptor antagonist, losartan has been reported to be without effect on blood pressure in salt-replete normals. Salt restriction together with furosemide for 3 days led to dose-related falls in blood pressure in normal subjects after losartan 25-100 mg. Concentration-effect analysis can be used to describe blood pressure responses, to predict the responses to long-term treatment and also to identify quantitatively important factors determining the response in individual patients. PMID- 8498976 TI - [Clinical findings with inhibitors of the renin-angiotensin system]. AB - Cardiovascular diseases are often associated with increased activity of the systemic and/or local renin-angiotensin systems. Hence, with respect to the coronary vessels, it has been demonstrated that in patients with severe heart failure inhibition of the renin-angiotensin system with an angiotensin converting enzyme (ACE) inhibitor clearly reduces resistance in the systemic, renal and cardiovascular systems. This reduction in resistance improves the blood supply to the failing heart while, at the same time, diminishing the external workload. It is most likely this effect that contributes towards the improved progression of the underlying disease observed after ACE inhibitor administration. The clinical efficacy of ACE inhibitors in patients who had been subjected to repeated coronary angioplasty has, however, been disappointing. Although these agents exerted a clear inhibitory effect on neo-intima proliferation after balloon dilatation performed on animals, it was not observed in patients with coronary artery disease and did not prevent restenosis. In patients suffering from heart failure there is an increase in sympathetic tone and a decrease in parasympathetic tone. An increase in activity of the renin-angiotensin system produces an increase in sympathetic activity at the level of the peripheral sympathetic synapses and vagus blockage via its effect on the vagal centres in the postremal area. Both effects can be clearly diminished by administering ACE inhibitors. Although high sympathetic tone and low parasympathetic activity are indicators of low life expectancy in heart failure, a clear correlation between the incidence of sudden cardiac death and the changes in autonomic nervous system activity has not yet been established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8498977 TI - [The use of angiotensin converting enzyme inhibitors in practice]. AB - Angiotensin converting enzyme (ACE) inhibitors have been accepted as drugs of first choice in the treatment of hypertension beside beta-blockers, diuretics and calcium antagonists. ACE inhibitors are effective, well tolerated and produce a small rate of adverse effects. They may be used in mild, moderate and severe hypertension of essential or renal origin regardless of age and sex. Since long term studies are missing, knowledge is lacking whether ACE inhibitors have the same beneficial effects on cardiovascular morbidity and mortality as diuretics and beta-blockers. ACE inhibitors represent one of the best established and documented therapies of chronic congestive heart failure. When ACE inhibitors are added to the conventional treatment of congestive heart failure, the mortality will be reduced in all states of congestive heart failure. PMID- 8498978 TI - Inhibitors of the renin-angiotensin system. AB - Inhibition of the renin-angiotensin system with angiotensin-converting enzyme inhibitors is well established as a treatment modality for hypertension and congestive heart failure. While converting enzyme inhibitors are well tolerated, they still have some side effects, which rightly or wrongly are attributed to the lack of specificity of the target enzyme for the renin-angiotensin cascade. The attempt is therefore made to inhibit the more specific enzyme renin or to block the angiotensin II receptor. While so far renin inhibitors are generally hampered by insufficient oral bioavailability, potent orally active angiotensin II antagonists are currently in clinical development. Both pharmacologic principles, renin inhibition and angiotensin II antagonism, have been shown to actively reduce blood pressure of hypertensive patients. It remains to be seen whether these newer compounds will be able to replace the converting enzyme inhibitors and exhibit even fewer untoward effects. PMID- 8498979 TI - Building partnerships: culinary groups offer opportunities for spreading the nutrition message. PMID- 8498980 TI - Croup and related disorders. PMID- 8498981 TI - Response to Lundberg's "Perspective" in the April 1992 Bulletin. PMID- 8498982 TI - Success rates for rehabilitation of vascular amputees: implications for preoperative assessment and amputation level. PMID- 8498983 TI - Reconsideration of the routine and preferential use of lidocaine in the emergent treatment of ventricular arrhythmias. PMID- 8498984 TI - Comment on 'A distribution-moment model of energetics in skeletal muscle. PMID- 8498985 TI - Closure of wounds under tension with the pulley suture. PMID- 8498986 TI - Initial preparations for amalgam. PMID- 8498987 TI - Actuarial five-year survival estimates. PMID- 8498988 TI - Breast augmentation and the risk of subsequent breast cancer. PMID- 8498990 TI - Protein structure prediction. PMID- 8498989 TI - Breast augmentation and the risk of subsequent breast cancer. PMID- 8498991 TI - Regulated medical waste: is any of it infectious? PMID- 8498992 TI - Bilateral surface coils in MR breast imaging: potential hazards. PMID- 8498993 TI - Noninvasive diagnosis of idiopathic dilated cardiomyopathy. PMID- 8498994 TI - Gemfibrozil-lovastatin-associated myalgia. PMID- 8498995 TI - Some considerations on reversible dilated cardiomyopathy due to thyrotoxicosis. PMID- 8498996 TI - Brain damage following hyponatremia: what is the determinant? PMID- 8498997 TI - Does acyclovir worsen late varicella? PMID- 8498998 TI - Pretraining for international medical graduates. PMID- 8498999 TI - Headaches in children younger than 7 years: are they really benign? PMID- 8499000 TI - Postoperative pain thresholds. PMID- 8499001 TI - Use of the laryngeal mask and face mask by inexperienced personnel. PMID- 8499002 TI - Reverse digital artery flaps: a note of caution regarding cold intolerance. PMID- 8499003 TI - Castleman disease in POEMS syndrome with elevated interleukin-6. PMID- 8499004 TI - The attribution of lung cancer to asbestos. PMID- 8499005 TI - Inflammatory abdominal aortic aneurysm. PMID- 8499006 TI - Sherlock Holmes. PMID- 8499007 TI - Promoting primary care: where to start? PMID- 8499008 TI - OSHA breaks a rule. PMID- 8499009 TI - High cholesterol levels in patients with panic disorder. PMID- 8499010 TI - Assessing the risk of airway obstruction following laryngeal mask insertion. PMID- 8499011 TI - Anaesthetists, nurses and pre-operative visiting. PMID- 8499012 TI - Modification to the Sprotte spinal needle. PMID- 8499013 TI - Clinical relevance of raised soluble serum interleukin-2 receptor concentrations in cystic fibrosis. PMID- 8499014 TI - Recurrent parotitis. PMID- 8499015 TI - The application of results of some studies of California Seventh-Day Adventists to the general population. PMID- 8499016 TI - Letting vegetative patients die. PMID- 8499017 TI - Urodynamic investigation in elderly women. PMID- 8499018 TI - Diversion from custody. PMID- 8499019 TI - Toronto clinic takes new approach to neurologic injury, damage. PMID- 8499020 TI - Enhancement of complement-mediated killing of Neisseria gonorrhoeae by antibodies to lipopolysaccharide of Escherichia coli J5. PMID- 8499021 TI - Psychosocial support during high-risk pregnancy. PMID- 8499022 TI - Endocrine effects of HIV infection. PMID- 8499023 TI - The efficacy of optic nerve sheath decompression for anterior ischemic optic neuropathy and other optic neuropathies. PMID- 8499024 TI - Control of bacteria in dental water supplies. AB - A simple device which releases chlorhexidine acetate into dental unit water supplies is described. The device comprised methyl methacrylate resin containing 40% by weight of chlorhexidine powder, cast into a rod shape and placed in a reservoir. After initial cleaning by flushing with hypochlorite, five dental units were fitted with the device and five units acted as controls. The device successfully kept four units virtually free of bacteria over a 3-month period but effective cleaning of the tubing within the units was found to be essential for success. Sustained release of chlorhexidine offers one means of tackling the problem of contaminated water in dental units, without resorting to complex pumping or metering systems. PMID- 8499025 TI - Managing urinary tract infection. PMID- 8499026 TI - Undergraduate medical education. AB - Pressures from students and teachers, from professional bodies, and from changes in the way health care is delivered are all forcing a rethink of how medical students should be taught. These pressures may be more intense in London but are not confined to it. The recommendation the Tomlinson report advocates that has been generally welcomed is for more investment in primary care in London. General practitioners have much to teach medical schools about effective ways of learning, but incentives for teaching students in general practice are currently low, organising such teaching is difficult and needs resources, and resistance within traditional medical school hierarchies needs to be overcome. Likewise, students value learning within local communities, but the effort demanded of public health departments and community organisations is great at a time when they are under greater pressure than ever before. The arguments over research that favour concentration in four multifaculty schools are less clear cut for undergraduate education, where personal support for students is important. An immediate concern is that the effort demanded for reorganising along the lines suggested by Tomlinson will not leave medical schools much energy for innovating. PMID- 8499027 TI - Peak bone mass and osteoporosis prevention. AB - The incidence of osteoporotic fractures increases with advancing age. Despite advances in therapy, reversal of bone loss in established osteoporosis remains problematic and deformities and disability due to fractures often persist. Therefore the logical approach to osteoporosis treatment is preventive. Risk of fracture is determined largely by bone density, which is the end result of peak value achieved at skeletal maturity and subsequent age- and menopause-related bone loss. Thus the determinants of peak bone density and bone loss require full characterization. Environmental and lifestyle factors are important determinants of bone density, particularly physical activity and diet. For example, muscle strength and physical fitness predict bone density, so that regular moderate exercise may help maintain bone mass but probably does not reverse loss. Long term calcium intake appears to be important for achievement and maintenance of peak bone density, especially in males. Smoking and excessive alcohol intake are deleterious to bone mass. Cultural norms in diet, lifestyle and physical activity obviously have an impact on bone density. Genetic factors have a strong role in determining the wide range in 'normal' peak bone mass. Moreover we have found strong genetic determinants of rates of change of bone mass in the lumbar spine and similar trends for sites in the femoral neck. We have shown previously that genetic factors influence bone turnover indices, particularly osteocalcin. Investigating these relationships with restriction fragment length polymorphisms, we have identified variants of the vitamin D receptor gene which predict osteocalcin levels and presumably bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499028 TI - Undergraduate medical education. PMID- 8499029 TI - Toxic shock syndrome after minor surgery. PMID- 8499030 TI - Managing urinary tract infections. PMID- 8499031 TI - Toronto clinic's new approach. PMID- 8499032 TI - Decision support systems for diabetes management. PMID- 8499033 TI - [The complement system: a fascinating biological chain of events]. PMID- 8499034 TI - Chronic heart failure in the community. PMID- 8499035 TI - [Subjective cognitive disorders in schizophrenia]. AB - The current status of the subjective cognitive disorders (SCD) in schizophrenia is examined Hypothetically, SCD are ascribed to impairments of information processing, however studies on the relationship between SCD and information processing are scarce and contradictory. The psychometric properties of most SCD' scales are not enough studied, but they seem to have a high interrater reliability, internal consistency and concurrent validity. The number of SCD is related to female sex, and inversely to educative level and the lack of insight into illness. In the acute stage of illness, the SCD are associated to positive symptoms and they can then reflect the process activity of the schizophrenia. In the remission stage of illness, the SCD are related to negative symptoms and they are the subjective experience of the psychological deficit. A theory of the SCD in the framework of the vulnerability/stress model of schizophrenia is proposed. PMID- 8499036 TI - Who won't tell: predictors of refusal to report number of sex partners. AB - Data from 1475 respondents to a telephone survey are used to examine whether those who refused to report the number of their sex partners in the 12-month period prior to the interview are more likely to engage in HIV risk behaviours than those who did report this number. Logistic regression shows that refusal is associated with being single of low education (OR(adj) = 8.0, 95% CI 2.7-23.7), using condoms in the last year (OR(adj) = 4.2, 95% CI 1.6-11.1), self-reporting of HIV-risk behaviours (OR(adj) = 3.6, 95% CI 1.3-9.6), and being male (OR(adj) = 2.7, 95% CI 1.1-6.6). These associations apply only to a subsample of individuals who provided complete information for HIV risk and other related behaviours. Results from the total sample indicate that individuals in our study who did not report their number of partners are more likely to have characteristics that are compatible with a higher probability of HIV risk practices. This pattern of associations suggests that refusers are indeed at higher risk for HIV infection than those sexually active individuals who did report the number of partners. PMID- 8499037 TI - Focal cortical dysplasia in children with localization-related epilepsy: EEG, MRI, and SPECT findings. AB - A retrospective analysis was conducted of 9 children with focal cortical dysplasia and localization-related epilepsy who underwent epilepsy surgery. Focal cortical dysplasia includes malformed lesions with extensive abnormalities of neuronal morphology, architecture, and lamination. The patients were examined by EEG and video EEG telemetry, CT, MRI, and SPECT using 99mTc-HmPAO. EEG disclosed interictal localized epileptiform activity in 8 patients and nonepileptiform activity with slow waves in 1. Ictal EEG telemetry demonstrated a predominantly localized seizure onset in 8 patients and MRI demonstrated an abnormal loss of gray and white matter distinction in 6. Decreased regional cerebral blood flow (rCBF) was detected in 4 patients by interictal SPECT, and increased rCBF in the same epileptogenic focus in 2 by postictal SPECT. Pathologic analysis found focal cortical dysplasia in 8 patients. One had extensive focal polymicrogyria, pachygyria, and extensive white matter heterotopias. It is concluded that MRI can detect focal cortical dysplasia, which corresponds to the epileptogenic focus on EEG, and SPECT may help to detect a functional abnormality in the same region. PMID- 8499038 TI - Natural history of ventricular dilatation in preterm infants: prognostic significance. AB - Cerebral ultrasounds were prospectively performed in 100 infants weighing 1,500 gm or less in order to evaluate the prognostic significance of ventricular dilatations and their associated findings. There was no difference in the incidence of ventricular dilatation (24%) between patients with or without periventricular hemorrhage (PVH). Although patients with PVH developed ventricular dilatation significantly earlier than infants without PVH, no differences were observed in severity, location, head circumference growth, or intracranial pressure between the groups. Ventricular dilatation was statistically related to PVH grade III and PVH with parenchymal involvement; grades moderate-to-severe of periventricular echogenicity; and cystic periventricular leukomalacia (PVL). Ventricular dilatation persisted longer than 6 weeks in 61% of infants and had irregular margins in 62%. The latter were significantly related to cystic PVL. Seventy-seven of 100 infants examined were followed until 20 months corrected age. Ventricular dilatation mainly when persistent and with irregular margins was associated with handicaps. We conclude that ventricular dilatation is frequent in very low-birth weight infants. Furthermore, its occurrence may be independent of PVH. Persistent ventricular dilatation with irregular margins, even in its mild forms, suggests a parenchymal lesion and guarded prognosis. PMID- 8499039 TI - Neurologic findings in neonates with intrauterine cocaine exposure. AB - To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function, 30 term infants were evaluated prospectively: 14 cocaine exposed and 16 unexposed. Cocaine-exposed infants had significantly lower mean birth weights, birth lengths, and head circumferences than urine-negative controls. Neurologic abnormalities among cocaine-exposed newborns included hypertonia of any type (86% vs 33%), axial hypertonia (79% vs 19%), plantar extension (46% vs 19%), and coarse tremor (57% vs 12%). The degree of hypertonia was sufficiently severe to warrant a diagnosis of "hypertonic tetraparesis" in 64% of cocaine-exposed and 12% of unexposed infants (P = .007). This diagnosis was highly correlated to small head size (r = 0.48; P = .01). Persistent tonic downward gaze was evident in two neurologically abnormal cocaine-exposed newborns. Gaze abnormalities improved slightly over the next 3 weeks of observation. One such infant re-evaluated at 6 months of age revealed resolution of tonic downward gaze and neurologic findings. We conclude that prenatal cocaine exposure is associated with tone and movement abnormalities in newborn infants. PMID- 8499040 TI - Multiple syndromes of 3-methylglutaconic aciduria. AB - The most common clinical syndromes associated with 3-methylglutaconic aciduria are presented. In some patients these syndromes are multisystemic, progressive disorders of unknown etiology. Tissues deriving significant energy through oxidative metabolism (notably brain and cardiac muscle) are most often affected and in some the primary defect may reside within the mitochondrial respiratory chain. Although increasing biochemical evidence suggests that 3-methylglutaconic aciduria may correlate with deranged mitochondrial energy metabolism, the biochemical origin of 3-methylglutaconic acid and the significance of its increased excretion remain unknown. This review describes these syndromes and illustrates the necessity of urinary organic acid analysis to assist in the differential diagnosis. PMID- 8499041 TI - EKG abnormalities in pediatric patients with myotonic dystrophy. AB - Electrocardiographic (EKG) abnormalities are frequent in patients with myotonic dystrophy; cardiac complications may lead to significant morbidity and mortality. The charts of 17 pediatric patients with myotonic dystrophy were reviewed to ascertain the frequency of EKG abnormalities and cardiovascular symptoms. Fifteen of 17 patients had abnormal EKGs with sinus bradycardia being the most common abnormality. Only 1 of 17 patients had cardiovascular symptoms. Four patients had moderate to severe weakness and 3 of them had a conduction disturbance (i.e., first-degree AV block or intraventricular conduction delay). Two of the remaining 13 patients with mild weakness had conduction disturbances. No pediatric patients had progressive EKG abnormalities during follow-up. Baseline EKG study of pediatric patients with myotonic dystrophy is recommended because abnormalities are frequent and usually asymptomatic. Frequent follow-up EKGs are probably unnecessary unless the patient is symptomatic or has heart block. PMID- 8499042 TI - Ventriculitis in infants: diagnosis by color Doppler flow imaging. AB - A color Doppler flow imaging technique was used to study the dynamics of cerebrospinal fluid (CSF) in infants with meningitis. Eight infants with bacterial meningitis (6) or aseptic meningitis (2) were studied with color Doppler imaging of CSF flow for a total of 18 times. In 2 infants with bacterial meningitis, Doppler sonograms of CSF flow were obtained in the aqueduct during the acute stage. The CSF flow demonstrated a to-and-fro motion which was synchronized with cardiac pulsations and respiration. The detection of CSF flow on color Doppler flow imaging in the aqueduct may indicate the existence of ventriculitis. Color Doppler flow imaging is useful for the evaluation of CSF flow dynamics in infants. PMID- 8499043 TI - Predictive value of placebo methylphenidate. AB - The effects of methylphenidate in 20 children with attention-deficit disorder between the ages of 7 and 12 years were assessed in a double-blind, placebo/drug counterbalanced study. Measures of outcome included the Teacher Rating Scale and Abbreviated Parent Rating Scale: digits, words, and visual sequencing; motor control; and a maze test. The Teacher Rating Scale placebo-drug difference correlated more significantly with the outcome measures than the baseline-drug difference. The study underlines the validity of a multimeasure placebo/drug trial in evaluating the efficacy of methylphenidate in children with attention deficit disorder. PMID- 8499044 TI - Neonatal glycine encephalopathy: biochemical and neuropathologic findings. AB - A patient with neonatal glycine encephalopathy who had severe neurologic retardation, spasticity, and seizures died at 17 years of age. Glycine concentration was markedly elevated in brain tissue, especially in the cerebellum. Neuropathologic study revealed spongy myelinopathy throughout the central nervous system and calcium oxalate crystals in the cerebellum, which are probably derived from degradation of glycine. Myelinopathy appeared to be static compared to neonatal patients. The neurologic manifestations of neonatal glycine encephalopathy are probably due to neurotransmitter abnormalities, not to myelin damage. PMID- 8499045 TI - Lipoma on surface of centroparietal lobes. AB - A 4-year-old Japanese boy with an intracranial lipoma above the surface of the left centroparietal lobes is reported. Paresthesia occurred in the right lower extremity. This symptom continued for 30 min and recurred several times a day. Three weeks after onset, the paresthesia disappeared spontaneously. Ten months after onset, generalized tonic seizures occurred. Routine cranial computed tomography at onset revealed no remarkable lesion, but subsequently full scans, including the slice at the top of the cerebrum, revealed low-density areas on the surface of the left centroparietal lobes. T1-weighted magnetic resonance imaging revealed a hyperintense area in the same regions. The intensity of these areas was decreased by the fat saturation technique; therefore, an intracranial lipoma at a very rare site was diagnosed. PMID- 8499046 TI - Association of progressive myoclonic epilepsy and spinal muscular atrophy. AB - It is well known that certain hereditary diseases of the nervous system sometimes occur concurrently within particular families. This report presents a Yugoslav family of Hungarian origin in whom 2 brothers had progressive myoclonic epilepsy and proximal weakness and atrophy of muscles. Electromyography and muscle biopsy confirmed neurogenic atrophy. Electroencephalography disclosed paroxysmal spike and-wave and polyspike-and-wave complexes with photic-induced myoclonic jerking. The combination of these clinical features is extremely rare and probably constitutes a clinical syndrome that has not been reported previously. PMID- 8499047 TI - Childhood polymyositis as a paraneoplastic phenomenon. AB - Childhood polymyositis and dermatomyositis are rare conditions that are not generally associated with malignancy even though an association between adult onset and malignancy has been reported. A child is presented with typical polymyositis in whom an immunoblastic sarcoma subsequently became manifest; the literature also is reviewed concerning the association between malignancy and these childhood conditions. PMID- 8499048 TI - Burkitt's lymphoma presenting as Tolosa-Hunt syndrome. AB - An 11-year-old girl presented with acute, severe symptoms resembling Tolosa-Hunt syndrome. Response to corticosteroids was rapid and satisfactory, but of short duration. Cranial magnetic resonance imaging demonstrated a supra- and parasellar mass and the abdominal ultrasound demonstrated a round tumor. Histopathologic study of the abdominal mass revealed Burkitt's lymphoma. PMID- 8499049 TI - Benign paroxysmal tonic upward gaze. PMID- 8499050 TI - Approach to diagnosis of oxidative metabolism disorders. AB - Mitochondrial oxidation of a variety of substrates produces the bulk of energy requirements for most cell types. Impairment of oxidative metabolism may result in a broad spectrum of clinical signs and symptoms. A disorder of oxidative metabolism should be suspected when an unexplained association of signs and symptoms occurs, particularly when it is progressive, involving organs with no common embryologic origin. Encephalopathy and myopathy are a particularly suspect combination. Numerous specific disorders affect oxidative metabolism. Lactate elevation frequently occurs and additional laboratory abnormalities often assist in focusing investigation. Diagnostic specificity may require, in addition to the blood and urine studies, tissue sampling, cerebral imaging, in vivo studies of tissue energetics, or molecular genetic analysis. PMID- 8499051 TI - Does phenobarbital used for febrile seizures cause sleep disturbances? AB - The effect of phenobarbital on total sleep time, night awakenings, and lengthy awakenings was examined as part of a randomized trial of children with febrile seizures; information about sleep patterns was gathered by parental observation. Children were between ages 8-36 months at enrollment and were examined subsequently for 2 1/2 years. Night awakenings were not more common in children assigned to phenobarbital except for those who were poor sleepers at the beginning of the study. Total sleep time was no different in children assigned to phenobarbital than in those assigned to placebo. It is concluded that sleep problems reported in most young children with febrile seizures treated with phenobarbital did not exceed those reported in children treated with placebo, but a subset of predisposed children did experience an increase in night awakenings. PMID- 8499052 TI - Standardized lung function testing. Official statement of the European Respiratory Society. PMID- 8499053 TI - Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. PMID- 8499054 TI - Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. PMID- 8499055 TI - Airway responsiveness. Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. PMID- 8499056 TI - Symbols, abbreviations and units. Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. PMID- 8499057 TI - Affinity immunoblotting studies on the restriction of autoantibodies from endemic pemphigus foliaceus patients. AB - Endemic pemphigus foliaceus or Fogo Selvagem (FS) is an autoimmune blistering skin disease mediated by autoantibodies directed against components on the surface of subcorneal keratinocytes. All patients have high titers of these autoantibodies in the IgG4 subclass as determined by indirect immunofluorescence on frozen skin sections. In addition, patients may also have autoantibodies in other IgG subclasses, particularly IgG1, but the titers in these subclasses are significantly lower than those found in the IgG4 subclass. We have now found that in addition to isotype preference, autoantibodies from FS patients show clonal restriction as evidenced by oligoclonal banding on isoelectric focusing after probing with extracts from both human and bovine epidermis. Both IgG1 and IgG4 exhibit oligoclonal banding, but the distribution of these bands in the pH gradient differs for these two subclasses. Whereas the IgG4 oligoclonal bands are distributed throughout the IgG4 pH range, IgG1 banding appears to be concentrated in the more basic region of the IgG1 pH range. This finding suggests that the IgG1 autoantibodies have undergone selective somatic mutation by a negatively charged autoantigen. Similar findings have been reported for pathogenic DNA autoantibodies associated with SLE. The wide distribution of IgG4 banding suggests that this response may have followed the IgG1 response and has not undergone selective mutation. Both IgG1 and IgG4 appear to be Ca++ dependent autoantibodies. PMID- 8499058 TI - Association of ANCA isotype and affinity with disease expression. AB - The association of ANCA isotype and affinity with disease expression is reviewed and new data on IgA ANCA levels and affinity in relation to disease activity are presented. Differences in the IgG ANCA subclass distribution exist between active disease and remission, with high affinity IgG3 ANCA present at the onset of disease. IgM ANCA, with or without associated IgG ANCA, correlates with pulmonary haemorrhage and disappears at remission. IgA ANCA are mainly found in patients presenting with Henoch-Schonlein purpura (HSP), and are directed against a distinct autoantigen of approximately 50 kD. The level and affinity of IgA ANCA also correlate with disease activity in HSP. Isotype as well as antibody specificity appear to be major determinants of disease expression. PMID- 8499059 TI - ANCA anti-idiotype antibodies and the treatment of systemic vasculitis with intravenous immunoglobulin. AB - The presence of anti-idiotype antibodies (anti-id) to anti-neutrophil cytoplasm autoantibodies (ANCA) in intravenous immunoglobulin (IVIg) and remission sera from patients with systemic vasculitis, and the use of IVIg as an alternative therapeutic agent in open studies, has suggested a role for idiotypic regulation in the normal control of these disorders. Clinical benefit with IVIg has been reported in 15/16 patients, with sustained remission in eight. The ability of IVIg to produce lasting remission has been associated with a fall in ANCA levels and stimulation of endogenous immunoglobulin production. IVIg has the potential to influence the pathogenetic process in patients with vasculitis at several stages, and an influence on the idiotypic regulation of ANCA may explain the observed clinical responses and point to possible targets for more specific immunotherapy in the future. PMID- 8499060 TI - Cellular immune responses and pathogenesis in c-ANCA positive vasculitides. AB - Very little is known about the cellular immune response in c-ANCA (classical anti neutrophil cytoplasm antibodies) positive vasculitides or Wegener's granulomatosis (WG). The present review is mainly based on published and unpublished observations of the Cattegat Study Group of Wegener's Granulomatosis. Immunohistochemical examinations of nasal biopsies from untreated patients with active WG revealed the presence of substantial amounts of cells belonging to the immune system (CD3+, CD4+, CD8+, CD20+, CD38+ and CD68+). The IgG response of peripheral mononuclear cells from untreated WG patients to PWM and EBV stimulation was significantly depressed when examined by the reverse haemolytic plaque forming cell assay. T lymphocyte proliferation was observed by in-vitro stimulation with extract of human neutrophil alpha granules, containing the autoantigen for c-ANCA, proteinase-3, only in patients with c-ANCA and active disease. Electron microscopy of biopsies from nasal lesions in untreated patients with active WG did not show structural abnormalities of the organelles of macrophages, giant cells or epithelioid cells. It is concluded that the immune response leading to c-ANCA production involves the full spectrum of immunocompetent cells normally engaged in IgG production to a foreign antigen. This would be in agreement with a theory of cross reactivity of proteinase-3 with a microbial antigen as a pathogenetic mechanism. PMID- 8499061 TI - The role of the endothelium in systemic vasculitis. AB - The critical role played by the vascular endothelium in the development of vasculitic disease will be discussed within this article, attention being focused on the pathogenesis of the primary vasculitides, particularly Wegener's granulomatosis, microscopic polyarteritis and Kawasaki disease. Under normal circumstances the endothelium constitutes a barrier to the efflux of plasma proteins into the extracellular tissues, serves to maintain an anti-coagulant environment and forms a platform upon which many important biological processes take place. Alteration of the balance of these functions by inflammatory mediators and cytokines leads to the formation of a pro-coagulant environment, fluid leakage and increased adhesivity of the endothelium for neutrophils and lymphocytes. Both neutrophils and lymphocytes have the capacity to damage the endothelium directly, by the secretion of oxygen radicals, enzymes and other cytotoxic molecules, or indirectly by the secretion of cytokines which may alter the biological properties of endothelial cells, a process called endothelial activation. The role played by antibodies to the endothelium and to neutrophil cytoplasm components in mediating vascular injury in systemic vasculitis is also discussed and, finally, injury precipitated by components of the coagulation/thrombotic system. PMID- 8499062 TI - Pre-emptive renal transplantation in children and adolescents. AB - Forty-three out of 204 children received their first renal transplant without prior dialysis. In order to evaluate the outcome of pre-emptive transplantation, two groups were compared retrospectively. The groups consisted of 28 children who received their transplants either without prior dialysis (ND) or after a varying period of dialysis (D). They were matched by age, year of transplantation, immunosuppressive regimen, donor source, and original disease. The percentage of living related donors was 50% in each group. Patient survival was identical in both groups; one patient died in each group due to infection in the early post transplantation period. The 5-year graft survival rates were 89% in the ND group versus 72% in the D group. The functional parameters graft function, anemia, hyperparathyroidism, hypertension, and the growth rates tended to be slightly better in the ND group than in the D group. The differences, however, were not significant. We conclude that pre-emptive transplantation is a safe procedure that shortens the period of uremia and is, therefore, recommended for children with end-stage renal failure. PMID- 8499063 TI - Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile. AB - The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69 +/- 0.20, post 0.84 +/- 0.23, P < 0.05), lower serum cholesterol levels (pre 6.8 +/- 1.0, post 5.8 +/- 1.2, P < 0.05), lower mean arterial pressure (pre 111 +/- 14, post 102 +/- 8, P < 0.05) and a lower hypertension index (pre 2.45 +/- 2.77, cur 1.62 +/- 1.70, P < 0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly. PMID- 8499064 TI - Intestinal distribution of hyaluronan in small bowel allografting in the rat. AB - Hyaluronan (hyaluronic acid; HA) was demonstrated and quantified in small bowel tissue at different times after small bowel transplantation. Semiallogeneic or semisyngeneic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease (GVHD). In normal rat small bowel, HA was present in the villous lamina propria and around medium-sized vessels in the interstitium of the crypt area. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt area where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection, and on day 6 there was a threefold increase compared to the values in syngeneic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. In specimens from animals suffering from GVHD, no significant changes in water or HA content and distribution were observed until day 12. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value in differentiating between graft rejection and GVHD. PMID- 8499065 TI - Gastrointestinal surgical emergencies following kidney transplantation. AB - This study reports major gastrointestinal complications in a group of 416 patients following kidney transplantation. Three hundred and ninety-nine patients received a cadaveric kidney while the other 17 received a living related organ. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, and cyclosporin. Perforations occurred in the colon (n = 6), small bowel (n = 4), duodenum (n = 2), stomach (n = 1), and esophagus (n = 1). There were five cases of acute pancreatitis, four of upper gastrointestinal and two of lower intestinal hemorrhage, two of acute appendicitis, one of acute cholecystitis, one postoperative mesenteric infarction, and two small bowel obstructions. Fifty percent of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or episodes of acute rejection. Ten percent of the complications had an iatrogenic cause. Of the 31 patients affected, 10 (30%) died as a direct result of their gastrointestinal complication. This high mortality appears to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications can be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol. PMID- 8499066 TI - Early prediction of renal allograft loss beyond one year. AB - Despite significant improvements in the results of renal transplantation since the introduction of cyclosporin, graft loss beyond the 1st year remains a significant and unresolved problem. In a retrospective analysis, 348 cyclosporin treated renal transplant recipients with a functioning graft at 12 months were studied. Forty-eight patients in whom graft failure occurred in the 2nd and 3rd years were compared to 300 patients who maintained graft function beyond this time. Both groups were comparable with respect to donor and recipient features. Factors reflecting recipient immunological responsiveness--sensitization, previous transplantation and early rejection episodes--continued to affect graft survival beyond the 1st year. Surprisingly, there was a higher incidence of prior transfusion in the group with graft failure in the 2nd and 3rd years than in those with longer function (65% vs 24%). Serum creatinine levels at 3 and 6 months were also predictive of graft loss amongst patients with a functional graft at 1 year. It remains to be answered whether new immunosuppressive drugs and strategies will overcome these risks for late graft loss. PMID- 8499067 TI - Liver transplantation in patients with situs inversus. AB - Situs inversus has been considered an absolute contraindication to liver transplantation due to technical difficulties. Associated vascular malformation and distorted anatomy may make the procedure even more complicated or impossible. Only three cases of patients with abdominal situs inversus who underwent successful liver transplantation have been reported in the English literature. We describe two additional patients with situs inversus who suffered from biliary atresia and underwent successful liver transplantation. The preoperative evaluation and the operative procedure are presented, and technical difficulties are discussed. Since biliary atresia is associated with polysplenia syndrome, including vascular malformation and visceral malposition, we suggest that each case be extensively evaluated preoperatively to determine the size requirement for the donor liver and the feasibility of reconstruction. PMID- 8499068 TI - Aortoiliac reconstruction in preparation for renal transplantation. AB - Aortoiliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984-1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure. PMID- 8499069 TI - A plea for an algorithm. PMID- 8499070 TI - Prevention of transmission of HIV by organ and tissue transplantation. HIV testing protocol and a proposal for recommendations concerning donor selection. AB - Human immunodeficiency virus (HIV) can be transmitted by solid organ and some forms of tissue transplantation. Although routine screening of organ and tissue donors for anti-HIV antibodies was implemented in most Western European countries and North America in 1985, several recent case reports indicate that a definite, albeit very small, risk of HIV transmission still remains. The screening tests that are currently used cannot rule out a false-negative test result occurring during the window period. Moreover, massive transfusion of the donor during the donor procedure may result in an undetectable anti-HIV antibody titer (by dilution of donor blood) that consequently leads to a false-negative test result. These risks of HIV transmission via transplantation and important issues in HIV testing are discussed in detail. Furthermore, several recommendations for the prevention of transmission and a protocol for HIV testing for both organ and tissue donation are presented. These may serve as intermediary guidelines until official ones, such as already exist for blood donation, are defined by the transplantation communities. The exclusion of donors whose behavior may place potential recipients at risk for HIV infection is essential. A thorough heteroanamnesis of the donor's next of kin during the donor procedure should provide sufficient information about donor history to enable a decision to be made in this respect. Special attention is given to the question of whether the existing donor selection criteria for blood donation should be applied in a similar way to organ donation since the strict application of selection criteria may limit the number of available donor organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499071 TI - Partial kidney transplantation: a successful kidney transplantation in a child with severe cardiac failure by surgical mass reduction of an adult donor kidney. AB - We report on a trial of partial kidney transplantation performed on a low body weight child with impaired cardiac function due to mitral valve stenosis and uremic cardiomyopathy. The weight of the donated kidney was successfully reduced by one-third using bench surgery in order to obtain sufficient graft perfusion and function. Our procedure is justified when a graft is too large to be adequately perfused in a recipient suffering from cardiac failure. PMID- 8499072 TI - Dysarthria and cerebellar ataxia: late occurrence of severe neurotoxicity in a liver transplant recipient. AB - Neurological complications of cyclosporin (CyA) therapy are frequent, usually occurring within the 1st month after transplantation. Though leukoencephalopathy is one of them, it is rarely documented. Here we report the case of an anti-HCV positive patient with cirrhosis who underwent liver transplantation and developed cyclosporin-induced leukoencephalopathy. The presenting symptoms were dysarthria, difficulty walking, and dysphagia. They were first noted 6 months after transplantation in association with an episode of recurrent HCV acute hepatitis. White matter abnormalities were evident on computed tomography (CT) scanning and magnetic resonance (MR) imaging. This condition improved to some degree after cyclosporin withdrawal. To our knowledge this is the second reported case of CyA neurotoxicity occurring late after liver transplantation. Moreover, the association with acute hepatitis suggests the possibility of graft dysfunction as a contributing and triggering factor. PMID- 8499073 TI - Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation. A case report. AB - We discuss the case of a 30-year-old primipara woman who developed a liver rupture as a complication of the HELLP syndrome. A liver necrosis and bleeding made a hepatectomy necessary. A portocaval shunt was able to maintain the patient until she underwent urgent liver transplantation. In an excellent state of recovery, the woman and her baby were discharged from the hospital 66 days after having been admitted. PMID- 8499074 TI - A case for cytokines as effector molecules in the resolution of virus infection. AB - Some cytokines are known to have potent antiviral activity in vitro, and recent work shows that severely immunodeficient mice, which lack conventional effector T cells, can still recover from virus infection provided these factors are present at sites of virus replication. Here Alistair Ramsay, Janet Ruby and Ian Ramshaw discuss these findings and raise fundamental questions concerning the physiological role of cytotoxic T cells in the resolution of virus infection. PMID- 8499075 TI - Extracellular matrix proteins in intrathymic T-cell migration and differentiation? AB - Intrathymic T-cell migration and differentiation is not completely understood. Here, Wilson Savino and colleagues argue that certain interactions between differentiating thymocytes and thymic epithelial cells are mediated by extracellular matrix proteins and that these interactions influence intrathymic migration events and thymocyte differentiation. PMID- 8499076 TI - The cytokine wall chart. PMID- 8499077 TI - Interleukin 1 receptors in the brain and endocrine tissues. AB - Immune activation is often accompanied by profound alterations in neurological and endocrine function, such as fever, increased somnolence, decreased appetite, activation of the hypothalamic-pituitary-adrenal axis, and suppression of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes. These well-recognized systemic responses to injury and infection have been attributed to circulating pro-inflammatory cytokines, the best characterized of which is interleukin 1 (IL-1). Here Emmett Cunningham and Errol De Souza discuss the mechanisms by which blood-borne IL-1 might affect such changes in the nervous and neuroendocrine systems. PMID- 8499078 TI - Distinct roles for CD4 and CD8 as co-receptors in antigen receptor signalling. AB - The co-ordinated interactions of multiple membrane molecules with the T-cell receptor for antigen (the TCR-CD3) are prerequisite for T-cell activation. In this review we consider the involvement of CD4, CD8, and CD45 on the two lymphocyte lineages. Experiments from many laboratories have provided concordant results leading to the consensus that CD4 and CD8 are functional analogues, providing similar supplementary signals to those generated through the TCR-CD3 complex on MHC class-II- and MHC class-I-restricted T cells, respectively. However, recent results demonstrate striking differences in the coreceptor functions of CD4 and CD8. These differences reflect the distinct properties of the molecules themselves, which in turn are associated with CD45 involvement in the activation of CD4+ and CD8+ T cells. PMID- 8499079 TI - The roles of CD8 in cytotoxic T lymphocyte function. AB - The CD8 glycoprotein of cytotoxic T cells is both an adhesion protein and a cosignalling receptor. These functions are regulated by signals from the T-cell antigen receptor complex (TCR-CD3), and CD8 acts to couple TCR occupancy to second messenger pathways. Here Anne O'Rourke and Matthew Mescher examine the roles of CD8 in activating the adhesion and signalling cascade initiated by antigen binding. PMID- 8499080 TI - Cord-blood lymphocyte populations. PMID- 8499081 TI - [The risk approach and maternal mortality: a Latin American perspective]. AB - Maternal mortality in Latin America and the Caribbean is a health problem that reflects the existing inequalities in the Region, as expressed in the loss of more than 28,000 women every year as a result of abortions and complications of pregnancy, childbirth, and the puerperium. This situation is associated with the limited coverage and low quality of health and family planning services and, in particular, with the tremendous unmet need for family planning services in many countries of the Region. The risk approach is proposed as an effective method for enhancing health care, especially in the area of maternal and child health. Systematically applied, this method will help to improve reproductive health. PMID- 8499082 TI - [Attitude and behavior regarding breast self examination among health professionals in Chile]. AB - This study was carried out from April to December 1990 in the commune of Valdivia, Chile and involved 207 physicians, nurses, midwives, and nurse midwives. The objective was to determine the relationship between subjective attitude and personal behavior on the part of these health professionals with regard to the practice of monthly breast self-examination (BSE). The data were collected by means of an instrument designed to measure attitudes, which was prepared by Victoria Lee Champion (1984) on the basis of the health beliefs model of Becker, et al. (1974). Also included were questions aimed at ascertaining the personal and sociodemographic background of the professionals surveyed and their knowledge of several aspects of breast cancer and BSE. The information collected was subjected to the following tests of validity and reliability: Person product moment correlation coefficient r, split half method, Spearman-Brown R coefficient, Cronbach alpha coefficient, and the Chi-square test to determine the degree of association between the variables. The results showed that although 79% of the women studied had ample knowledge of many aspects of breast cancer and 82% were aware of the benefits of BSE, only 28% practiced it on a monthly basis. It is alarming that health professionals, who are responsible for teaching prevention measures to other people, have yet to assume responsibility for protecting their own health insofar as early detection of breast cancer is concerned. PMID- 8499083 TI - How the first enzyme electrode was invented. PMID- 8499084 TI - The Dutch Biosensor Research Program. PMID- 8499085 TI - Polymer membrane-based ion-, gas- and bio-selective potentiometric sensors. AB - Recent progress in the design of new polymer membrane-based potentiometric ion-, gas- and bio-selective electrodes in chemistry laboratories at the University of Michigan (Ann Arbor) is reviewed. Emphasis is placed on describing the performance of devices for measuring anions (e.g., salicylate, thiocyanate, chloride and heparin) and gases (e.g., ammonia, carbon dioxide and oxygen) in biological samples, both in vitro and in vivo. Beyond direct measurement of key ions and gases in complex matrices, some of the new membrane electrode systems reported can serve as base transducers for the development of biosensors containing integrated biological reagents, including enzymes and antibodies. New approaches for mass fabricating solid-state ion and biosensor devices as well as future directions for research in the entire field of polymer membrane sensors are also described. PMID- 8499086 TI - Study of immunoglobulin G thin layers obtained by the Langmuir-Blodgett method: application to immunosensors. AB - Nowadays, immunosensors play a leading part in the field of bioanalytical chemistry research. As with any biosensor, they need appropriate transducers and a suitable technique to immobilize the active biocomponents. In this study, two transduction modes were chosen: mass effects (quartz microbalance measurements) and geometric and dielectric effects (capacitance measurements). The Langmuir Blodgett (LB) method appears to be quite suitable for generating biospecific surfaces. This work has focused on the detection of staphylococcal enterotoxin B, the corresponding antibody being immobilized at the surface of fatty acids by a variant of the LB method. The composition of the film and the nature of antibody fatty acid interactions were studied by means of the two transducers mentioned above. FTIR (Fourier transform infra-red) spectroscopy and protein diagnostic assay. Influence of several parameters (pH, ionic strength, transfer pressure, antibody concentration in the subphase) was investigated. The immobilization rate reached its maximum when experimental conditions allowed optimal electrostatic interactions. In this case, the quartz crystal microbalance response, in air, reached 55 Hz per monolayer of immobilized immunoglobulin G and the equivalent capacitance variation, measured in liquid media, was around 300 pF cm-2. Activity of the biospecific LB films, when binding enterotoxin, was checked by the classical ELISA (enzyme immuno-linked assay) technique. PMID- 8499087 TI - An activated sludge-based biosensor for rapid IC50 estimation and on-line toxicity monitoring. AB - The RODTOX (Rapid Oxygen Demand and TOXicity tester), an activated sludge-based respirographic biosensor, is a device for on-line monitoring of the short-term biochemical oxygen demand (stBOD) and potential toxicity of incoming wastewater on the basis of on-line interpretation of respirograms resulting from pulse additions of either calibration substrate or sample. The principle of toxicity detection is based on the comparison of calibration respirograms before and after receiving a potential toxicant. In this paper, the results of the RODTOX as an on line toxicity monitor are presented. In addition, a simple and fast procedure to estimate the IC50 of a toxicant has been developed, and its validity and good repeatability demonstrated. The performance of this procedure is compared with that of the Microtox test. PMID- 8499088 TI - Three-dimensional imaging for evaluation of head and neck tumors. AB - OBJECTIVE: To determine the usefulness of three-dimensional imaging in addition to computed tomography in presurgical examination of patients with head and neck tumors. DESIGN: Two-dimensional computed tomographic information from 31 patients with oral facial tumors was converted to three-dimensional images. SETTING: University teaching hospital. PATIENTS OR OTHER PARTICIPANTS: A consecutive sample of 31 patients with oral facial tumors. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Improved treatment planning with the use of three-dimensional images used in conjunction with computed tomographic scans. RESULTS: The three dimensional images from patients with minimal tumor invasion of bone or with massive soft-tissue tumors allowed easy appreciation of tumor dimensions, an important factor in treatment planning. In patients with small soft-tissue tumors with no evidence of bone involvement on two-dimensional scans, massive tumors with complete bone destruction, and recurrent tumors, the three-dimensional representations added little to the obvious presentation of the two-dimensional scans. CONCLUSIONS: Three-dimensional imaging is a useful adjunct to diagnosis and treatment planning in patients with minimal tumor invasion of bone or with massive soft-tissue tumors. PMID- 8499089 TI - Regional chemotherapy for recurrent squamous head and neck cancers through a saphenous vein interposition graft. AB - Regional chemotherapy for head and neck cancers is effective, but the intra arterial catheter is not without problems. We interposed a segment of saphenous vein within the carotid system to administer chemotherapeutic agents percutaneously via the arterialized venous segment. From 1983 to 1990, saphenous vein interposition graft was performed after radiotherapy in 24 patients with persistent or recurrent squamous head and neck cancers, which were also considered unresectable. There was no operative mortality. Two patients developed thrombosed vein graft; another two had wound infection; and one patient had a neck hematoma. Cisplatin was administered percutaneously every week via the saphenous vein graft. The response rate was 64% (complete response, 23%; partial response, 41%), and the 5-year actuarial survival rate was 31%. The 1-year survival rates for patients with complete, partial, and no response were 80%, 33%, and 13%, respectively. Saphenous vein interposition graft is a safe and convenient way of delivering intra-arterial chemotherapy, and it provides significant palliation for patients with recurrent nonresectable squamous head and neck cancers after radiotherapy. PMID- 8499090 TI - Comparison of intra-arterial and intravenous infusion of cisplatin for head and neck squamous cell carcinoma in a modified rat model. AB - To study intra-arterial infusion of chemotherapeutic agents, human squamous carcinoma cells were obtained from the FaDu cell line and were implanted in athymic rats (rnu/rnu). The xenografts were grown and then were reimplanted on a vascular pedicle and were completely isolated from the surrounding tissue. The vascular isolation of these pedicles was confirmed radiographically and histologically. After 26 days of growth, an osmotic pump was implanted to deliver either saline, intra-arterial cisplatin, or intravenous cisplatin to the vascular pedicle. Platinum levels were identified in the tumors following intra-arterial and intravenous infusions, demonstrating the usefulness of this model for delivery of antineoplastic agents. We were unable to detect differences between tumor groups for final tumor volume, tumor platinum levels, and tumor histology with the one-dose schedule used. We were able to show a remarkable uniformity of the tumor platinum levels with varying serum platinum levels with intra-arterial and intravenous infusion of cisplatin. The toxicity of each drug administration method was assessed by levels of renal platinum and rat serum creatinine and blood urea nitrogen. No differences in toxicity with the dose administrated. We believe the immunodeficient rat with a xenografted isolated vascular pedicle is an excellent model to study the effect of intra-arterial therapeutic modalities on head and neck squamous cell carcinoma. PMID- 8499091 TI - Perforating osteotomies in rhinoplasty. AB - While perforating lateral osteotomies have been previously described by other authors, most of the current literature emphasizes only sliding lateral osteotomies. Therefore, we present our experience with 106 consecutive rhinoplasties performed with perforating lateral osteotomies with a minimum 2 year follow-up. The perforating lateral osteotomy technique used in these rhinoplasties is described in detail and is compared with those techniques previously reported for perforating lateral osteotomies in rhinoplasty. Anatomical considerations are discussed. The results with the perforating lateral osteotomy technique have been excellent and are also presented. We think that perforating lateral osteotomies are an important and useful part of the rhinoplasty armamentarium. PMID- 8499092 TI - The treatment of rhinophyma. 'Cold' vs laser techniques. AB - OBJECTIVE: To compare laser surgery and sharp blade excision of rhinophyma. DESIGN: Retrospective study of 23 patients treated surgically for rhinophyma. SETTING: Four academic tertiary referral medical centers. PARTICIPANTS: All 23 patients had moderate or major rhinophyma. INTERVENTION: Sixteen patients had laser surgery. Seven patients had sharp blade excision. OUTCOME MEASURES: Length of the procedure, preservation of normal tissue, the need for skin grafting, intraoperative pain and discomfort, intraoperative bleeding, postoperative pain and discomfort, postoperative bleeding, complications, and end results (all listed in the literature as advantages of laser surgery). RESULTS: No difference in length of surgery, preservation of normal tissue, complications, postoperative pain, and end results. No need for skin grafting in both procedures. Less intraoperative and postoperative bleeding, easier and smoother procedure, and more comfortable postoperative care with laser surgery. CONCLUSIONS: Our results do not agree with most of the list of advantages attributed to laser rhinophyma surgery in the literature. PMID- 8499093 TI - Small incision laser lift for forehead creases and glabellar furrows. AB - A new technique for eliminating or reducing glabellar frown lines and forehead creases with a small (3- to 5-cm) incision, KTP (potassium [K]-titanyl-phosphate) laser (Laserscope), and endoscope (Karl Storz) has been performed on 62 patients over the last 18 months. This endolaser technique takes advantage of the unique properties of the frequency-doubled Nd:Yag (neodymium:yttrium aluminum garnet) (KTP) laser coupled with an optimized quartz contact probe. It enables the surgeon to incise or excise the procerus, corrugator, and frontalis muscles, with little or no bleeding, at a distance from a small incision immediately behind the hairline. This small incision frontal lift has been as effective as the standard forehead lift in rejuvenation of the upper face, avoiding the paresthesias, scalp itch, headaches, periorbital ecchymosis, and hair loss that are common sequelae of the forehead lift. Recovery time has been markedly reduced. PMID- 8499094 TI - Finite element analysis of airflow in the nasal valve. AB - We digitized the outline of the nasal cavity from images obtained after applying contrast material to the nose. A computer-aided simulation of flow was undertaken in the sagittal plane in the anterior nasal cavity. Previous work on the nasal valve was reviewed. Our results showed that the nasal valve is an oblique structure bounded laterally by the caudal end of the upper lateral cartilage, medially by the septum, and ventrally by the inferior rim of the piriform aperture. We found that this rim, projecting from the floor of the nose, produces an uneven distribution of airflow through the valve with most of the flow occurring in the ventral segment. Removal of this rim should result in a more even distribution of flow across the valve. PMID- 8499095 TI - Ciliary beating frequency in chronic sinusitis. AB - Ciliary beating frequency, one component of mucociliary function, was measured outside of the sinus in vitro with a photoelectric method in 150 patients with chronic sinusitis and in 26 control subjects. In the mucosal samples of 35 patients (23%), no ciliary activity was seen. Ciliary beating frequency in maxillary sinus mucosa of the rest of the 115 patients (77%) was, as an average, 16.6 +/- 3.0 Hz (range, 10.9 to 23.3 Hz) and it was 15.9 +/- 2.6 Hz (range, 13.2 to 22.8 Hz) for the control patients. No differences in ciliary beating frequency were found according to quality of sinus secretion, prevalent respiratory allergy, or mucosal thickness. However, in sinuses with purulent secretion, ciliary beating frequency was slightly better (P < .05) than in "empty" sinuses. The study suggests that in many cases of chronic sinusitis, the sinus mucosa still has a capacity to recure. PMID- 8499096 TI - Erythromycin therapy for otitis media with effusion in sinobronchial syndrome. AB - Chronic sinusitis is frequently associated with chronic lower respiratory tract diseases, and the association is referred to as sinobronchial syndrome (SBS). This study was carried out to determine the incidence of otitis media with effusion in the patients with sinobronchial syndrome and to investigate the efficacy of low-dose and long-term erythromycin therapy for otitis media with effusion associated with sinobronchial syndrome. We have found a high incidence of otitis media with effusion in patients with sinobronchial syndrome, the morbidity rate being 54% in 50 cases studied. This ear disease seems to be the major cause of hearing disturbance in patients with sinobronchial syndrome. Sixteen patients with both sinobronchial syndrome and otitis media with effusion were given low-dose and long-term erythromycin therapy (erythromycin base, 600 mg/d for more than 4 months); of these, 13 became effusion-free and most subjects showed improvement in the symptoms of sinobronchial syndrome. The erythromycin therapy thus seems to be exceedingly effective for the treatment of sinobronchial syndrome and associated otitis media with effusion. PMID- 8499097 TI - Synthetic prostaglandin E1 misoprostol as a treatment for tinnitus. AB - OBJECTIVE: A pilot study to determine if the synthetic prostaglandin E1 misoprostol is effective in treating severe tinnitus, to test the hypothesis that tinnitus production is related to prostaglandin metabolism. DESIGN: Blinded, placebo controlled, hemicrossover. SETTING: House Ear Clinic, Los Angeles, Calif. PATIENTS: A volunteer and convenience sample of 24 subjects complaining of severe tinnitus was recruited from mailings, telephone calls, and the clinic population. The patients were not preselected except to be in otherwise good health. INTERVENTION: Subjects were started on a regimen of placebo or 200 micrograms/d of misoprostol. The dosage was increased every 5 days by 200 micrograms until a total of 800 micrograms/d was achieved. After 1 month of drug administration, the placebo group was crossed over to the active drug phase. MAIN OUTCOME MEASURES: Outcome was measured in terms of subjective reports of tinnitus severity, sleep patterns, and ability to concentrate. RESULTS: Eight (33%) of the 24 patients reported improvement during the active drug phase. There were no placebo responders. Responders reported improvement in tinnitus severity, sleep, and concentration. CONCLUSIONS: Findings support the contention that prostaglandins may be useful in the treatment of tinnitus. Further studies with larger samples are needed before widespread use of this intervention can be recommended. PMID- 8499098 TI - High-frequency monitoring for early detection of cisplatin ototoxicity. AB - Cisplatin can cause irreversible hearing loss initially detectable as impairment of high-frequency hearing with progression to lower frequencies. Many patients receiving cisplatin are too ill to tolerate lengthy audiometric testing. Therefore, a rapid and sensitive high-frequency monitoring strategy to detect cisplatin-induced ototoxicity is needed. Serial conventional (0.25 to 8 kHz) and high-frequency (> or = 8 kHz) threshold monitoring was performed in patients receiving cisplatin, resulting in 84% of ears showing hearing loss, of which 71% were detected first in frequencies of 8 kHz or greater. By analysis according to an individualized, specific high-frequency range, early identification of hearing loss occurred in 94% of ears showing change. This five-frequency procedure is a sensitive detector of ototoxicity and is proposed as an alternative monitoring protocol for patients receiving cisplatin who cannot tolerate extended testing. PMID- 8499099 TI - The cause of aural polyps in children. AB - This 20-year retrospective review identifies 35 pediatric patients with aural polyps in an attempt to assess for clinical predictors of significant otopathologic conditions. Chronic otitis media (43%), cholesteatoma (29%), and retained tympanostomy tubes (23%) were the common causes. Unusual causes included mycobacterial infection and Langerhans' cell histiocytosis. Multivariate analysis revealed the co-occurrence of conductive hearing loss at presentation to be a significant clinical predictor (P = .03) of cholesteatoma; the histopathologic finding of keratin-induced giant cell reaction was nonspecific in this respect. Cholesteatoma was also prevalent in recurrent polyp cases, suggesting the need for prolonged follow-up in those children whose initial clinicopathologic evaluation does not yield a definitive diagnosis. PMID- 8499100 TI - Neonatal otitis media. An update. AB - Neonatal otitis media may be an isolated infection or part of a more complex sepsis syndrome. Because early studies suggested that the microbiologic characteristics of neonatal otitis media included a high risk of gram-negative coliforms and Staphylococcus aureus, tympanocentesis was recommended routinely. Subsequent studies have supported empiric medical therapy in selected patients, reserving tympanocentesis for patients in whom medical treatment fails. Because of these conflicting recommendations, records from 37 neonates with otitis media who underwent tympanocentesis from 1986 through 1991 were studied retrospectively. Cultures in one outpatient (11%) and four inpatients (13%) yielded Escherichia coli, all of which were sensitive to amoxicillin. No cultures of S aureus were identified. Sterile cultures and pneumococcus isolates were found most frequently. No septic or intracranial complications were noted. All patients were discharged on regimens of routine antibiotics for otitis media. PMID- 8499101 TI - Carbon dioxide laser serial microtrapdoor flap excision of subglottic stenosis. AB - The recent development of microspot micromanipulators for the carbon dioxide laser with 250-microns spot sizes has greatly facilitated the extension of endolaryngeal procedures to children and neonates. It is possible to accurately develop microtrapdoor flaps within the limited exposures in the pediatric subglottis. We have used serial microtrapdoor flaps in the excision of subglottic scar tissue in eight children. In five children, the stenosis was improved with relief of stridor. In three children, the flaps were used as an adjunct to laryngotracheoplasty. The surgical techniques of this procedure are detailed in this report. PMID- 8499102 TI - Sensorineural hearing loss associated with birdshot retinochoroidopathy. AB - We treated a patient with birdshot retinochoroidopathy, an autoimmune eye disease. An autoimmune sensorineural hearing loss developed, probably due to endolymphatic hydrops. To our knowledge, the association of these two conditions has not been recorded previously. PMID- 8499103 TI - Acute otitis media with transient sensorineural hearing loss. A case study. AB - A patient had acute otitis media with transient sensorineural hearing loss. Early symptoms included otalgia, progressive sensorineural hearing loss, and tinnitus with inflammation of the tympanic membrane. During the second week a conductive component emerged resulting in a 60-dB mixed loss in the 2- to 4-kHz region. The conductive component lasted 15 days while the sensorineural hearing loss recovered more slowly, with complete recovery at 6 months. Audiologic measures included conventional and extended high-frequency audiometry, 226-Hz and multifrequency tympanometry, binaural speech recognition, auditory brain-stem response, and psychoacoustic tuning curves. PMID- 8499104 TI - Simultaneous presentation of malignant external otitis and temporal bone cancer. AB - Malignant external otitis and squamous cell carcinoma of the external auditory meatus are both characteristically seen in the older population. While some of the signs and symptoms of these two diseases are similar (otalgia, otorrhea, bone destruction on computed tomographic scan), they have rarely been reported in the same patient. We present an unusual case of temporal bone cancer and malignant external otitis presenting concurrently in an elderly, nondiabetic host. Precipitating factors and diagnostic criteria are discussed. This case illustrates the importance of an adequate biopsy specimen in all patients presenting with presumed "classic" malignant external otitis. Consideration must also be given for the existence of malignant external otitis in the presence of carcinoma. Finally, evolution of malignant external otitis in this patient following aural irrigation supports previous suggestions that this disease may be induced iatrogenically. PMID- 8499105 TI - Mycosis fungoides involving the cervical esophagus. AB - Review of the otolaryngologic literature reveals no case reports of mycosis fungoides involving the esophagus. Post-mortem studies report 12 cases of esophageal involvement in 131 autopsies of patients with mycosis fungoides. We describe a 54-year-old man with mycosis fungoides involving the larynx, hypopharynx, and esophagus. Treatment consisted of radiation to this area, with resolution of the patient's hoarseness and dysphagia. The charts of 96 patients with mycosis fungoides treated at our institution were retrospectively reviewed. Three additional cases involving the aerodigestive tract, but not the esophagus, were found. Esophageal mycosis fungoides was an incidental finding in two of seven autopsies at our institution. PMID- 8499106 TI - E-PTFE (Gore-Tex) suspension cervical facial rhytidectomy. AB - Restoration of a well-defined, youthful-looking, cervicomental angle is not easily achieved. The classic rhytidectomy is now often supplemented by lipectomy and platysmamodifying procedures. Still, irregularities of neck contour are bothersome, and for the short, stocky neck, results at times fall short of a patient's and surgeon's expectation. Insertion of an E-PTFE (expanded polytetrafluorethylene [E-PTFE]; tradename, Gore-Tex, W. L. Gore Associates Inc, Flagstaff, Ariz) soft-tissue patch as a sling to support the floor of the mouth and redefine the cervicomental angle for a smoother neck contour is described. This method was used in seven patients presenting with problematic aging neck. The first three patients needed readjustment of the E-PTFE membrane. This evolving method seems to offer a superior, more lasting result for the correction of an obtuse cervicomental angle. PMID- 8499107 TI - Pathologic quiz case 2. Chordoma. PMID- 8499108 TI - Pathologic quiz case 1. Capillary hemangioma. PMID- 8499109 TI - Right hemisphere performance and competence in processing mental images, in a case of partial interhemispheric disconnection. AB - The objective of this study was to analyze dynamic aspects of right hemisphere implementation in processing visual images. Two tachistoscopic, divided visual field experiments were carried out on a partial split-brain patient with no damage to the right hemisphere. In the first experiment, image generation performance for letters presented in the right visual field (/left hemisphere) was undeniably optimal. In the left visual field (/right hemisphere), performance was no better than chance level at first, but then improved dramatically across stimulation blocks, in each of five successive sessions. This was interpreted as revealing the progressive spontaneous activation of the right hemisphere's competence not shown initially. The aim of the second experiment was to determine some conditions under which this pattern was obtained. The experimental design contrasted stimuli (words and pictures) and representational activity (phonologic and visuo-imaged processing). The right visual field (/left hemisphere: LH) elicited higher performance than the left visual field (/right hemisphere, RH) in the three situations where verbal activity was required. No superiority could be found when visual images were to be generated from pictures: parallel and weak improvement of both hemispheres was observed across sessions. Two other patterns were obtained: improvement in RH performance (although LH performance remained superior) and an unexpectedly large decrease in RH performance. These data are discussed in terms of RH cognitive competence and hemisphere implementation. PMID- 8499110 TI - Configural coding, expertise, and the right hemisphere advantage for face recognition. AB - Expertise in recognizing faces is associated with configural coding and configural coding is associated with a right hemisphere advantage for face recognition. Therefore one would expect the orientation-specific LVF (left visual field) advantage for face recognition to be moderated by expertise. The present experiments examined the effect of expertise with face ethnicity on the LVF advantage. In Experiment 1 subjects showed expertise-related use of configural coding, but no orientation-specific LVF advantage. In Experiment 2 subjects with high hemispheric arousal asymmetry showed an orientation-specific LVF advantage, but no expertise-related use of configural coding. Low arousal asymmetry subjects showed the opposite pattern. These results suggest that different kinds of configural coding may underlie ethnicity-related expertise effects and laterality effects in face recognition. PMID- 8499111 TI - Hemisphere and gender differences in mental rotation. AB - Hemisphere and gender differences in mental rotation for tachistoscopically presented stimuli were assessed in 40 right-handed university students. Twenty male and 20 female subjects each were individually administered (via computer) a mental rotation task which included 10 stimulus presentations at each of eight angular disorientations (0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees) in each visual half-field (VHF) for a total of 160 trials. Analyses of variance performed on reaction time and accuracy data revealed only a main effect for orientation. A typical mental rotation function for both the left VHF and the right VHF for both genders resulted; however, no gender x visual field interaction was found. Lack of hemisphere and gender differences provide further evidence questioning the interpretation of right-hemisphere male superiority for spatial tasks. Investigation into factors such as task complexity, stimulus familiarity, and task demands may lend further insight into hemisphere and gender differences in mental rotation. PMID- 8499112 TI - Spatial memory in alcohol-dependent subjects: using a push-button maze to test the principle of equiavailability. AB - The principle of equiavailability states that once the locations in a spatial array are learned, then all locations in the array are simultaneously available in memory (Levine, Jankovic, & Palij, 1982). To test the application of this principle, 21 nonamnesic, alcohol-dependent, male subjects and 20 demographic and ability-matched male control subjects were required to learn a series of push button maze paths and to perform shortcut or retrace movements on the paths. The results for the control subjects conformed to the principle of equiavailability. In contrast, the alcohol-dependent subjects did not show equiavailability. This pattern of results is interpreted as evidence of a spatial memory deficit in the alcohol-dependent subjects. PMID- 8499113 TI - Perceptual processing of pattern goodness by left and right hemispheres. AB - Two experiments tested perceptual processing of Garner and Clement's (1963) good and poor five-dot patterns by the left and right hemispheres. Two (good) patterns were from four-member equivalence sets, and the other (poor) pattern was from an eight-member equivalence set. One of the good patterns formed a T shape that could be processed as a linguistic unit. In Experiment 1, 80 right-handed subjects made same-different judgments for lateralized 200-msec paired presentations of these patterns. When both presentations were to the RVF/LH, response latency was faster for the T pattern than for the other two. When both presentations were to the LVF/RH, response latency was faster for the two good patterns than for the poor pattern. When the first pattern was presented to the RVF/LH and the second was presented to the LVF/RH, response latencies were lower for the two good patterns than for the poor pattern. Also, when the first pattern was presented to the LVF/RH and the second was presented to the RVF/LH, response latency was faster for the T pattern than for the other good pattern which was, in turn, faster than for the poor pattern. Experiment 2 used a duration judgment task (Avant & Lyman, 1975) to test effects of pattern goodness on apparent durations of pre- and postmasked 10-msec pattern presentations. With left hemisphere inputs, presentations of good patterns were judged to be longer than presentations of the poor pattern. When each hemisphere compared the T and the other good pattern, presentations of the T pattern were judged to be longer, and the right hemisphere further discriminated among pattern orientations. Presentations of the T pattern to each hemisphere were judged to be longer than presentations of the poor pattern, and both hemispheres discriminated among orientations of both patterns. These results indicate that the two hemispheres can, during perceptual processing, function cooperatively, and that both prerecognition and conscious perceptual operations are guided by task demands. PMID- 8499114 TI - Episodic effects on picture identification for alcoholic Korsakoff patients. AB - Experience with degraded pictures produces better subsequent identification of these pictures in amnesic patients. To examine the contribution of episodic memory to this facilitation, we compared identification of pictures that were identical to a studied picture, pictures that shared the same name with a studied picture, and new, unstudied pictures. In an initial phase of the experiment, patients clarified each picture until they could name it. During a second phase, they again clarified each picture and judged whether it was identical, similar (same-name), or different from pictures identified in the first phase. Korsakoff patients, as well as alcoholic controls, identified identical pictures faster than same-name pictures, and these in turn were identified faster than new pictures. The Korsakoff patients did show less facilitation than the alcoholic controls, but this difference was eliminated by testing the alcoholics after a week delay. The smaller facilitation in performance shown by amnesics and by alcoholics tested after a delay was accompanied by impaired recognition memory as well as by qualitative differences in recognition performance. The Korsakoff patients tended to label same-name pictures as different while alcoholic controls tested immediately called them identical, a tendency which disappeared when alcoholics were tested after a delay. These findings suggest that Korsakoff patients are influenced by specific episodic information even more than are alcoholic controls. PMID- 8499115 TI - [Mechanism of action of nitrates]. AB - Nitrates' mechanisms of action are reviewed focusing on are reviewed its hemodynamic effects on the systemic circulation and particularly on the coronary circulation. The beneficial effect of its use is discussed both in angina pectoris and heart failure clinical situations. These drugs mechanisms of action are described, particularly at cellular level, explaining its importance as exogenous suppliers of nitric oxide, and the location of its receptors is discussed. Particular attention is given to the tolerance phenomenon observed when they are used in clinical practice. PMID- 8499116 TI - [Nitrates in unstable angina]. AB - Unstable angina is an acute coronary syndrome between stable angina and myocardial infarction, with different clinical and laboratory features. Angiographically, these patients are more likely to have progression of coronary artery disease, vasospastic phenomena and intracoronary thrombus. Sudden plaque rupture, thrombus formation and the occlusion of an epicardial coronary vessel seem to be the underlying pathological mechanism. Patients with unstable angina are at an increased risk of major complications, especially fatal and nonfatal myocardial infarction, justifying an aggressive therapy in an Intensive Coronary Care Unit with beta-blockers, calcium antagonists and, in particular, nitrates, usually in association. The use of antiplatelet agents, namely aspirin, has been proved to be beneficial significantly reducing the risk of death and myocardial infarction. On the other hand, heparin and thrombolytic therapy are still a matter of some controversy, although the former is largely used in the acute phase. Coronary angiography should be done in all patients refractory to medical treatment to allow further management of the underlying coronary lesions by PTCA or coronary bypass surgery. However, some authors have advised a more aggressive attitude, performing the revascularization in an early phase. Randomized studies have shown that, with surgery, only patients with reduced left ventricular function may improve with the procedure, having a better two-year survival rate. Concerning PTCA, although the complication rate is somewhat higher than in the elective procedure, the probability of late infarction and death is significantly reduced in patients in which there was initial success. PMID- 8499117 TI - [Treatment of the acute phase of myocardial infarction with nitrates]. AB - An historical background of the use of nitrates in the setting of acute myocardial infarction gives way to the successive steps this therapy gave in the last 15 years. The pioneer investigations of John Flaherty proving the usefulness of nitroglycerin in reducing infarct size followed by the works by Bussman and Jugdutt notably on the limitation of infarct size but also on the prevention of infarct expansion and ventricular wall thinning are reviewed. The adjunctive role of nitrates in thrombolytic therapy is appraised and its absolute and relative contraindications are pointed out. Finally and based on the statistical works by Yusuf, the real impact of nitrate therapy in mortality of acute myocardial infarction is emphasised. PMID- 8499118 TI - [The use of oral and intravenous isosorbide mononitrate (5-MNi) in the acute phase of myocardial infarction]. AB - OBJECTIVE: To evaluate the hemodynamic effects of 5-IMN in acute myocardial infarct. DESIGN: Open trial. SETTING: Medical ICU at a general hospital. PATIENTS: 19 sequential patients with the diagnosis of AMI and clinical suspicion of pulmonary stasis, with a pulmonary capillary wedge pressure > 12 mmHg and a systolic blood pressure > 90 mmHg. INTERVENTIONS: No vasoactive drugs other than 5-IMN were given during the trial. The following parameters were measured at admission: heart rate (HR), mean blood pressure (BP) (indwelling arterial catheter), right atrial pressure (RAP), pulmonary arterial pressures (PAP), pulmonary capillary wedge pressure (PCWP) and cardiac output (CO). The cardiac index (CI), systolic index (SI), total peripheral resistances (TPR) and pulmonary vascular resistances (PVP) were calculated. The patients were started on 5-IMN either intravenous or oral accordingly to PCWP. The hemodynamic parameters were registered again at 30 min, 1 hour, 2, 6, 8, 24 and 48 hours and 5-IMN was stopped in all the following conditions: Severe hypoxia not improving with 5-IMN or requiring mechanical ventilation. Systolic blood pressure decreasing below 90 mmHg despite an adequate left ventricular filling pressure. Any other clinical condition forcing the use of other vasoactive drugs. MEASUREMENTS AND RESULTS: We discuss the hemodynamic parameters registered on admission and compare them with those obtained 48 hours after treatment with 5-IMN. The patients were divided in two groups according to PCWP: a group of 11 patients with 12 mmHg < PCWP < or = 18 mmHg who were given oral 5-IMN, and a group of 8 patients with PCWP > 18 mmHg and left ventricular failure, who were given an intravenous perfusion of 5-IMN in a dose that could keep PCWP < or = 18 mmHg. The differences between both groups are discussed. In patients with no left ventricular failure, 5-IMN decreased significantly PCWP and TPR, while increasing CO. In patients with PCWP > 18 mmHg there was also a decrease in PCWP and TPR and significant increases in both cardiac and systolic indexes. The decrease in BP was not significant in both groups. CONCLUSIONS: 5-IMN proved to be a safe drug when used during the first 48 hours of myocardial infarct even in patients with PCWP < or = 18 mmHg. It improved hemodynamics in all patients especially in those with left ventricular failure. PMID- 8499119 TI - [The use of nitrates in the treatment of heart failure]. AB - In this revision article, after referring the mechanisms of action of nitrates in the relief of heart failure symptoms, the author presents the results of the controlled studies which show the beneficial effect of the nitrates on heart failure symptoms and mortality. The results of the therapy with nitrates are compared to other heart failure therapies, such as the administration of the angiotensin conversion enzyme (ACE) inhibitors. In spite of the highly favourable results regarding mortality shown by the latest studies with ACE inhibitors, the nitrates still occupy an essential place in the therapy of patients with heart failure, since they have the advantage of a much faster onset of action and are more effective in relieving symptoms than ACE inhibitors. Finally, the author suggests some dosage and administration routes of the nitrates in heart failure. PMID- 8499120 TI - Microvasculature of growing and atretic follicles in the rabbit ovary: a SEM study of corrosion casts. AB - Rabbit ovarian microvasculature, with particular regard to developing and atretic follicles, was studied by scanning electron microscopy (SEM) of vascular corrosion casts. The microvascular network of the follicles was arranged in typical round plexuses of varying shape and size. Four different morphological types of vascular plexuses supplied the follicles: Type 1 (100-250 microns in diameter) consisted of a simple net of thin capillaries that delimited a small empty central cavity. Type 2 (diameter > 250 microns) consisted of a multilayered capillary wall delimiting a large empty central cavity. This wall presented an inner layer made of uniformly distributed dilated and tortuous capillaries with numerous angiogenetic sprouts. Type 3 (diameter of 100-300 microns) lacked the central cavity and comprised randomly arranged thin capillaries. Type 4 (diameter > 250 microns) consisted of a multilayered capillary wall delimiting a central cavity. Its inner layer was made of capillaries not homogeneous in size and course (thin in some areas, sinusoidal in others, sometimes highly dilated). In addition, the wall showed large interruptions (avascular areas) and focal invasion of the central cavity by newly formed vessels. Types 1 and 2 showed the gradual transformation of thin capillaries into sinusoids as has been demonstrated in evolutive follicles. Types 3 and 4, described here for the first time, probably represent the vascular supply to atretic follicles. In particular, Type 3 supplied follicles undergoing obliterating atretic degeneration, whereas Type 4 supplied atretic follicles with hypertrophy of the theca layer. In fact, follicular atresia is a pleiomorphic phenomenon which ends in a regression of the follicles (obliterant atresia), but which may induce a temporary follicular hyperactivation (luteinizing atresia). These changes in the microvasculature prelude the formation of the so called "interstitial gland of the ovary". Furthermore, these data prove that: 1) both thecal capillary vasodilatation and angiogenetic processes basically support the gradual increase of ovarian blood flow during follicle growth; 2) microvascular changes of atretic follicles are possibly related to a type of inflammatory reaction since they seem to be a consequential rather than primary cause of atresia. PMID- 8499121 TI - A histochemical study on glycoconjugates in epithelial cells in the distal colonic mucosa of adult and developing mice. AB - Glycoconjugates were histochemically studied in the distal colon of developing ICR mice in view of the presence of goblet and vacuolated cells. Alcian blue, high iron diamine and periodic acid-Schiff stainings were performed to characterize glycoconjugates. In addition, two lectins, Ulex europeus agglutinin I and Limax flavus agglutinin, were applied to detect fucosyl and sialyl residues, respectively. The reactivities to these stainings, noted from day 18 of gestation, did not seem to undergo any major change throughout their development. The present results suggest that: 1) goblet cells secrete sulfated glycoconjugates containing fucosyl and sialyl residues as terminal sugars; 2) vacuolated cells have glycoconjugates containing sialyl residues but no or few fucosyl residues nor sulfonic groups, and certain sialyl residues in the glycoconjugates are probably O-acetylated or O-acylated at least in part; and 3) the brush border of absorptive cells contains glycoconjugates sialylated and fucosylated to same extent but rarely sulfated. Since glycoconjugates elaborated by goblet and vacuolated cells differ from each other, one should be fully aware of the presence of these two types of mucin-producing cells in the distal colon. PMID- 8499122 TI - Fine structural changes in the postacrosomal region of the hamster and mouse sperm head at the initial stage of gamete interaction in vivo. AB - This report documents ultrastructural changes in the postacrosomal region of the hamster and mouse sperm head at the initial stage of gamete interaction in vivo. Prominent structures were sequentially visualized: first, the periodic substructure crossbridging the postacrosomal sheath to the overlying plasma membrane, and then the small, electron-dense, granular structures lining the outer surface of the postacrosomal sheath. The periodic substructure became visible at the restricted region where the sperm plasma membrane was just prior to or in the act of detaching from the periodic substructure. The granular substances lined up along the external face of the postacrosomal sheath immediately after the detachment of the sperm plasma membrane, but before the complete degradation of the periodic substructure. These structural changes were completed before sperm nuclear decondensation started. The region where the granular structures were visualized was close to that of the antigen recognized by the monoclonal antibody MN13, which is supposed to be involved in the association of the periodic substructure with the overlaying plasma membrane (Toshimor et al., 1991). Based upon these results, we present the progress of events at the initial stage of gamete interaction. PMID- 8499123 TI - Development of granule cells of the rat olfactory bulb: an autoradiographic and electron microscopic study. AB - The rate of migration of immature granule cells of the rat olfactory bulb and polarity of cell-organelles in the migrating granule cells were investigated by 3H-thymidine autoradiographic and electron microscopic methods. The time lag in migration between two points was determined by cross-correlation analysis of labeling indices of the two areas. Granule cells were estimated to take 6 days to migrate rostralwardly from the subependymal layer at the anterior wall of the lateral ventricle to the center of the bulb, and an additional 1 to 6 days to migrate radially from the subependymal layer to the granular layer of the bulb. These results showed that the rate of rostralward migration of granule cells was faster than that of their radial migration. Golgi-electron microscopic as well as routine electron microscopic studies on migrating granule cells revealed that centrioles and Golgi apparatus were located at the base of the leading process that possesses a growth cone at its tip. PMID- 8499124 TI - Functional morphology of the lymphatic system in the monkey diaphragm. AB - A morphological study of the lymphatic system in the diaphragm of adult Japanese monkeys was carried out using intraperitoneal injection with India ink, light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques. For SEM examination of the subperitoneal connective tissue, the peritoneal mesothelium was stripped by either the NaOH/sonication microdissection techniques or the NaOH digestion method. Light microscopy of 1 micron Epon sections and TEM of thin sections demonstrated that lymphatic capillaries were distributed in the subperitoneal connective tissue of the muscular and tendinous portions. Gaps (stomata) between neighboring cells of the peritoneal mesothelium were occasionally encountered. In SEM observations, stomata with oval shapes and various sizes were abundantly seen in the peritoneal mesothelium, but were absent from the pleural mesothelium. It deserves particular note that a large number of foramina were detected in the subperitoneal connective tissue. The cluster of the foramina was similar in appearance to the "macula cribriformis" depicted by KIHARA (1956). Carbon particles injected into the monkey peritoneal cavity passed through the peritoneal stomata and then the macula cribriformis, ultimately to enter the lymphatic capillaries. This paper also discusses the functional implication of the lymphatic system in the diaphragm. PMID- 8499125 TI - Scanning electron microscopy of tenotomized soleus muscles of the rat. AB - The effects of tenotomy on the surface morphology of muscle fibers including myotendinous junctions in the rat soleus muscle were studied by scanning electron microscopy (SEM). Using potassium hydroxide (KOH) and collagenase, the extracellular materials were successfully removed to expose the surface of muscle fibers. When the soleus muscle was tenotomized at both proximal and distal ends, virtually all muscle fibers showed marked alterations of the fiber surface characterized by the formation of numerous transverse grooves and folds along their length. Narrow longitudinal grooves and folds of the sarcolemma were also observed. At myotendinous junctions, the fiber ends showed an over-all rounded shape with several short sarcoplasmic processes, indicating that the processes were significantly retracted. These changes were clearly recognizable at 5 days after tenotomy, and most apparent at one week. Thin-section electron microscopy of the same SEM samples demonstrated that such folding of the sarcolemma was not directly related to the sarcomere pattern of the underlying myofibrils, suggesting that, once formed, the folds and grooves were retained for a certain period of time. At 2 and 3 weeks the surface morphology of the fibers underwent a recovery process of restoring the smooth surface on which the cross-striations of the underlying myofibrils were seen. At the fiber ends, sarcoplasmic processes regrew into slender, wavy and short forms. Such sarcoplasmic processes were greater in number and more elaborate than those in the control muscle. At 5 and 6 weeks the fiber surface resumed an almost normal morphology, except that the sarcoplasmic processes at the fiber end were still shorter and more numerous than those in the control. These observations support our previous results obtained by thin-section electron microscopy that the myotendinous junction undergoes a series of morphological changes of collapse and regrowth of the sarcoplasmic processes, reflecting changes in the underlying myofibrils. In conclusion, the changes in the surface morphology of tenotomized muscle fibers were well correlated chronologically to those of myofibrils such as the central core lesion. PMID- 8499126 TI - Three-dimensional structure of dog Sertoli cells: a computer-aided reconstruction from serial semi-thin sections. AB - The three-dimensional structure of the Sertoli cell in the Korean Jindo dog was investigated by scanning and transmission electron microscopy. Additionally, type A and type-B Sertoli cells were simulated by three-dimensional computer graphic imaging to clarify the anatomical relationship between Sertoli cell and germ cells. Descriptions in the present study are based on examination of the reconstructed type-A cells at stages IV, V and VI of the spermiogenetic cycle and stages VII, VIII and IX of the reconstructed type-B Sertoli cells. Morphologically, three types of Sertoli cell processes were evident: 1) flat club like, elliptical processes bifurcating and trifurcating randomly; 2) slender cord like, tubular processes; and 3) sheet-like processes. The sheet-like processes rested upon more than half the surface of each round spermatid located in the proximity of the Sertoli cell. Curiously, just before spermiation, the apical club-like processes shifted from their initial position at the spermatid head and subsequently covered the disengaged residual body, after which the residual body was no longer evident in the tubule. Though the mechanism for this elimination is not known, the process suggests a reciprocity between the Sertoli and germ cells. An anatomical dissimilarity between type-A and type-B Sertoli cells appeared in the apical region, with the apical club-like processes of the type-B Sertoli cell given off by sheet-like processes as well as by the Sertoli column. At the base of all Sertoli cells, sophisticated sheet-like processes paralleled the basal lamina, tenaciously adhering end-to-end to the sheet-like processes of adjacent Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499127 TI - Proliferation kinetics of macrophage subpopulations in a rat experimental pancreatitis model. AB - The kinetics of rat macrophage proliferation in the inflamed pancreas was analysed using a duct-ligation pancreatitis model. We performed a double immunostaining of pancreatic cryosections using a panel of monoclonal antibodies to either macrophage-specific (ED1, ED2) or macrophage-related (CR3 and Ia) antigens in combination with a cell marker of DNA synthesis (5-bromo-2' deoxyuridine, BrdU). One hour labeling with BrdU revealed each recorded macrophage phenotype to have a very high labeling index (12-28%), peaking on day 2 after induction of pancreatitis. The percentage of each proliferating phenotype also reached 20-40% of the total BrdU+ cells on day 2. The proliferating macrophages consisted of heterogeneous subpopulations including monocyte-like cells and resident macrophages. Their growth occurred in a relatively synchronized fashion, and seemed to be triggered by common proliferative signals. PMID- 8499128 TI - Species-differences in the process of apoptosis in epithelial cells of the small intestine: an ultrastructural and cytochemical study of luminal cell elements. AB - Our previous study demonstrated that in the small intestine of guinea pigs, apoptotic epithelial cells at the villus tips were phagocytosed by lamina propria macrophages, leaving only apical cytoplasmic plates, which thereafter were domed and extruded into the lumen. This finding contrasts with the generally accepted view that effete epithelial cells are simply exfoliated into the lumen. In order to explain this discrepancy, the present study examined luminal cell elements of the small intestine in the guinea pig, rat and mouse; the latter two have been favored species for studying the kinetics of intestinal cells. Light and electron microscopic observations indicated that the luminal fluid of the guinea pig contained numerous cytoplasmic fragments covered with long microvilli and not containing a nucleus; these fragments corresponded with the apical cytoplasm of apoptotic epithelial cells. In the rat and mouse, in contrast, luminal cell elements were represented by round cell bodies possessing a nucleus and microvillous border; the nucleus displayed compaction and segregation of chromatin at the periphery, a microscopic figure characteristic of apoptosis. As far as the rat and mouse are concerned, the present findings support the accepted view that epithelial cells undergoing apoptosis are exfoliated as total, nucleus containing cells. In the guinea pig, in contrast, only an apical thin plate of effete cells is shed off, as our previous studies have suggested. PMID- 8499129 TI - Sinusoidal vessels in the periodontal ligament of hamster incisors: their distribution, structure and possible function. AB - Vascular architecture in the periodontal ligament of hamster incisors was investigated by use of vascular casts under a scanning electron microscope (SEM). In addition to ordinary nutrient blood vessels, anastomosing vessels of large caliber developed, surrounding the incisor. From their characteristic configuration, these vessels were regarded as "sinusoids". The plexus of sinusoidal vessels was connected with capillaries in the papillary layer of the enamel organ at the labial periodontal ligament, and with veins penetrating into the alveolar bone on the lingual side. Transmission electron microscopic (TEM) observation showed that the sinusoidal wall was composed of only a thin layer of endothelial cells, lacking a smooth muscular element, and surrounded by densely arranged collagen fibers. Although the frequent association of Ruffini-type nerve endings with sinusoidal vessels was noted, neither direct contact nor specialized structures between these was recognizable. A possible function of the periodontal sinusoids is discussed on the basis of their distribution and ultrastructural evidence. PMID- 8499130 TI - Titanocendichloride activity in cisplatin and doxorubicin-resistant human ovarian carcinoma cell lines. AB - The activity of a new organometallic compound, titanocendichloride, was evaluated in doxorubicin- and cisplatin-resistant human ovarian carcinoma cell lines in vitro. Titanocendichloride showed no cross resistance to doxorubicin in two multidrug resistant sublines of A2780. Furthermore, the cell line A2780 CP3, which is about 20-fold resistant to cisplatin was only 2.5-fold resistant to titanocendichloride, indicating a lack of cross resistance between the two metal compounds. These results were confirmed in vivo where titanocendichloride showed a much stronger inhibitory effect in cisplatin-resistant human ovarian carcinoma xenografts than cisplatin. PMID- 8499131 TI - Non-organic somatic symptoms in cancer. AB - Somatic symptoms considered as unrelated to cancer or grossly out of proportion to the known pathology were systematically assessed in a group of 98 consecutively referred cases. Subjects with prominent somatic symptoms (somatisers) had depression (53%), anxiety (12%) and atypical somatoform disorder (27%). During follow-up, somatisers with depression showed clinical improvement whereas those with atypical somatoform disorder showed no improvement or deteriorated. Methods of distinguishing the cause of somatic symptoms in cancer patients are discussed. PMID- 8499132 TI - Trends in neuroblastoma in Great Britain: incidence and mortality, 1971-1990. AB - Incidence and mortality rates for neuroblastoma in Britain from 1971 onwards were examined using data from the population-based National Registry of Childhood Tumours. Incidence throughout 1971-1990 was within the range previously reported from Europe, North America and Oceania. The age-standardised rate rose, however, by 26% between 1971-1975 and 1986-1990, and there were increases of 36% both among infants aged under one year and also among children aged 1-9. There was a pattern of increasing risk with more recent years of birth up to 1985. It is implausible that improved diagnosis could explain the increase in rates since 1971, though it may account for a marked decrease in recorded incidence at the age of 10-14. Age-standardised mortality fell by 27% between 1971-1975 and 1981 1985, but rose again during 1986-1990. This was the result of a halt in the improvement in survival rates for neuroblastoma combined with a substantial and as yet unexplained increase in incidence. PMID- 8499133 TI - Platelet proaggregating activity of human colorectal tumour cell lines does not correlate with the degree of differentiation. AB - Six human colorectal tumour cell lines with various degrees of differentiation were studied. Each of the cell lines studied showed an in vitro platelet proaggregating activity, represented by the induction of typical aggregation waves. This activity was dose-dependent and probably related to a thrombin dependent mechanism. However, the degree of cell differentiation did not correlate with the proaggregating activity. In fact, significant differences were observed between the two well differentiated cell lines, while a comparison between well and poorly differentiated cell lines did not reveal any difference. These results were confirmed by the ultrastructural observations, indicating that similar platelet-tumour cell interaction may be found in all the cell lines studied. The present results suggest that platelet proaggregating activity of the human colorectal tumour cell lines under investigation is unrelated to their degree of differentiation. PMID- 8499134 TI - Potentiation of EO9 anti-tumour activity by hydralazine. AB - EO9[3-hydroxy-5-aziridinyl-1-methyl-2(1H-indole-4,7-dione)prop-bet a-en-alpha-ol] has been selected for phase I evaluation in Europe. Activity has been seen previously in a highly refractory, necrotic mouse adenocarcinoma (MAC 16) but EO9 is shown here to be inactive against early tumours (MAC 15A and MAC 13) and a well vascularised, well-differentiated established adenocarcinoma (MAC 26). EO9 becomes active against MAC 26 tumours when hydralazine (10 mg/kg) is administered 1 min after EO9. Co-administration of hydralazine decreases EO9 plasma clearance and increases plasma area under the curve values (0.053 to 0.115 micrograms h/ml). These pharmacokinetic changes are accompanied by anti-tumour activity but no increase in bone marrow toxicity so this therapeutic gain may be due, at least in part, to microenvironmental changes resulting from hydralazine induced tumour vascular shutdown. PMID- 8499135 TI - From triazines and triazenes to temozolomide. PMID- 8499136 TI - Is vasectomy a risk factor for prostate cancer? AB - Recently, several case-control studies have suggested that vasectomy may predispose to prostate cancer. Other studies have found no increase in risk. All of these studies have a number of limitations. Taken together, these studies do not provide convincing evidence that vasectomy increases the risk of prostate cancer. However, in view of the high prevalence of prostate cancer and the growing worldwide importance of vasectomy as a form of contraception, further epidemiological research is warranted. After briefly commenting on the experimental studies we will examine the epidemiological studies in more detail. This will be done by first summarising the designs and main findings of the most relevant published studies and then discussing methodological issues relating to the studies taken as a whole. Finally, we will present conclusions and offer recommendations for future research. PMID- 8499137 TI - Possible biological mechanisms for a relationship between vasectomy and prostatic cancer. AB - Four hypotheses have been reviewed, each of which might serve as a hypothetical biological explanation for a relationship between vasectomy and prostate cancer. The endocrine hypothesis is the only one of these with any firm data to support it, although the majority of the available data does not lend credibility to that theory. The other hypotheses are purely speculative with no hard data to support them. In conclusion, it seems highly unlikely, but not impossible, that there is a biological mechanism supporting a relationship between vasectomy and prostate cancer. PMID- 8499138 TI - Testicular cancer after vasectomy: origin from carcinoma in situ of the testis. AB - Vasectomy is a commonly used male contraceptive procedure. Reports have indicated that vasectomy is associated with an increased risk of development of germinal testicular cancer. Carcinoma in situ of the testis (CIS) is a preinvasive lesion which precedes germinal testicular cancer. CIS is almost always found in the tissue adjacent to a germinal testicular cancer. It is believed that CIS is a malignant gonocyte formed during embryogenesis. We have studied the testicular tissue from 5 previously vasectomised patients with testicular cancer and found CIS in the tissue adjacent to their cancer as well as changes in the epididymis of the patients. We discuss the findings and conclude that testicular cancers occurring after vasectomy is not an exception from the rule that testicular cancer originates from CIS. Thus, there is no causal relationship between vasectomy and testicular cancer, but vasectomy might precipitate the development of testicular cancer from the preinvasive CIS lesion. PMID- 8499139 TI - Vasectomy and testicular cancer: epidemiological evidence of association. PMID- 8499140 TI - Follow-up of breast cancer patients stage I-II. PMID- 8499141 TI - The correlation of proliferation rates to prognosis in human renal cell carcinoma. PMID- 8499142 TI - Myeloprotective effect of medroxyprogesterone acetate (MPA) PMID- 8499143 TI - Current issues in the management of clinical stage I testicular teratoma. PMID- 8499144 TI - Vasectomy and risk of cancers of prostate and testis. PMID- 8499145 TI - The therapeutic challenge of gliomas. PMID- 8499146 TI - Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. AB - Temozolomide, a new oral cytotoxic agent, has been given to 28 patients with primary brain tumours. Treatment was given at a dose of 150 mg/m2/day for 5 days (i.e. total dose 750 mg/m2) escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2/day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4 week intervals. A major improvement in computer tomography (CT) scan was noted in 5/10 patients with astrocytomas recurrent after radiotherapy, with a major clinical improvement but minor improvement on CT scan in one further patient. Reduction in the size of the CT lesion was also observed in 4/7 patients with newly diagnosed high grade astrocytomas given 2-3 courses of temozolomide prior to irradiation. 1 patient with recurrent medulloblastoma had a clinical response in bone metastases. Temozolomide was well tolerated with little subjective toxicity and usually predictable myelosuppression and is a promising new drug in the treatment of primary brain tumours. PMID- 8499147 TI - Chemotherapy administration and data collection in an EORTC collaborative group- can we trust the results? AB - As part of a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group, 15 centres took part in a programme to evaluate the quality of treatment delivered and data collected. The centres were visited and facilities for treatment and data management were reviewed. Source data in randomly selected patient hospital records were compared with information which had previously been completed on case record forms and returned to the EORTC Data Centre. The review included 71% of the patients entered into the study and 76% of the treatment cycles. Chemotherapy was prepared by nurses or clinicians in 58% and by pharmacists in 42% of the centres and was administered by specialist nurses in 67% of the hospitals. 8776 items were checked with source data. 3.4% were incorrect, 0.2% were missing and 30% could not be verified as correct (mainly related to the lack of recording of toxicity data in hospital records). The mean doses of chemotherapy delivered and treatment intervals were those stipulated in the protocol but 21% of the cycles were delayed for avoidable reasons. Several modifications to the procedures for running chemotherapy trials were suggested by this survey including the use of a systematic checklist for recording toxicity and chemotherapy administration and the development of quality assurance programmes in other collaborative groups and single centres to ensure that published results are credible. PMID- 8499148 TI - Indication and limits of megatherapy and bone marrow transplantation in high-risk neuroblastoma: a single centre analysis of prognostic factors. AB - 76 patients with high risk neuroblastoma were treated with one (41 patients) or two consecutive courses (35 patients) of megatherapy. Autologous bone marrow transplantation was scheduled after each megatherapy. Univariate analysis confirmed two prognostic factors in this heterogeneous study population: no bone lesions before megatherapy and age at diagnosis of less than 2 years with 5-year progression-free survival rates of 51% (P < 0.0007) and 53% (P < 0.025), respectively. Both factors were shown to be of independent prognostic significance using the Cox proportional hazard model. Identification of prognostic factors should help to define the interest and limits of megatherapy. We consider that elective megatherapy followed by innovative treatments appears justified in patients with persisting bone disease. In contrast, megatherapy has to be re-evaluated for patients showing a more favourable response pattern and/or young age, ideally in a randomised, prospective trial. PMID- 8499149 TI - Breast conserving therapy in patients with relatively large (T2, T3) breast cancers by preoperative irradiation and myocutaneous LD flap reconstruction. A new technique in breast conservation. AB - We investigated the feasibility of breast conserving treatment (BCT) in patients with large (T2, T3) breast cancers, by combining preoperative radiotherapy and tissue replacement after wide excision by a myosubcutaneous flap transposition. The treatment consisted of 50 Gy whole breast irradiation followed by a 15-25 Gy iridium implant to the primary tumour with 2 cm margins. Four weeks after completion of the radiotherapy, wide excision of the original tumour area with a 1 cm margin and an axillary dissection was performed. In the same session the breast was reconstructed with an ipsilateral latissimus dorsi transposition flap. The treatment results in the first 6 patients are encouraging with respect to treatment toxicity and cosmetic outcome. The clinical tumour response after radiotherapy was difficult to evaluate. However, microscopic evaluation showed residual tumour in all specimens with (focal) involvement of the surgical margins in two. With a minimum follow-up of over 2.5 years no tumour recurrences in the breast have occurred. PMID- 8499150 TI - CA 125 serum levels in the early post-operative period do not reflect tumour reduction obtained by cytoreductive surgery. AB - In order to assess whether CA 125 serum levels reflect the outcome of cytoreductive surgery, CA 125 antigen levels were determined prior to and after debulking surgery in 50 ovarian cancer patients and compared to CA 125 serum levels before and after surgery in a control group of 140 patients undergoing laparotomy for various malignant or benign diseases. A significant CA 125 decrease in the first post-operative week was seen in 56% of ovarian cancer patients whereas 26% remained stable and 18% showed a significant increase after surgery. Although removal of tumour had been complete in all 14 stage I-II ovarian carcinomas, only 2 of these patients showed a subsequent significant CA 125 decrease after cytoreductive surgery, while 4 patients showed a significant increase. Such increases of CA 125 following surgery were also seen in uterine carcinomas (30%), in gastrointestinal carcinomas (75%) and in patients after laparotomy for benign gynaecological diseases (23%). CA 125 pre-treatment levels were significantly lower in patients with post-operative increases than in patients with stable or decreasing CA 125 patterns. Patients with stable CA 125 levels also had lower CA 125 pretreatment levels compared to patients with a post operative CA 125 decrease. Post-operative increases were observed for at least 2 weeks after debulking in the case of ovarian cancer. Pre-operative levels of these patients were either within the normal range or moderately elevated. Serial measurements during surgery in partial debulking showed a rapid CA 125 decline within 24 h followed by increasing CA 125 values thereafter. Our data indicate that CA 125 serum levels in the direct post-operative period do not always reflect the outcome of cytoreductive surgery. There appears to be an effect on CA 125 levels caused by the abdominal surgical procedure itself. Consequently, CA 125 levels after abdominal surgery should be interpreted with caution. PMID- 8499151 TI - Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer. AB - The ability of oestrogen and progesterone receptor (ER and PgR, respectively) status to discriminate recurrence-free survival (RFS) among a cohort of consecutively accrued 952 postmenopausal patients has been studied. None of the cohort members investigated were treated with adjuvant therapy. Using a graduated scale of receptor status [low, intermediate and high receptor levels (< 10 vs. 10 107 vs. > or = 108 fmol/mg cytosol protein, respectively)] instead of the more commonly used dichotomous subdivision (positive vs. negative), ER level significantly discriminated between groups of patients with long vs. short RFS. Contrary to our expectations, patients with highest ER levels have as poor a prognosis as ER-negative patients, while patients with intermediate ER levels have longest RFS. The group of patients with ER levels > or = 108 fmol/mg cytosol protein comprises 47% of the cohort. The independent significance of overexpression of ER as a prognostic factor among this patient group is demonstrated in multivariate analysis where ER level is more significant than either grade of anaplasia or tumour size. PgR status did not significantly predict RFS among these patients. While the highest ER levels predispose for poorer prognosis among postmenopausal patients, it is precisely this group that experiences greatest benefit from adjuvant treatment with tamoxifen. Thus, patients who might otherwise go untreated due to their node-negative status can be readily identified and offered adjuvant treatment. PMID- 8499152 TI - Prognostic value of clinical, laboratory, and histological characteristics in multiple myeloma: improved definition of risk groups. AB - Follow-up data of 320 multiple myeloma (MM) patients entering the German Myeloma Treatment Group (GMTG) trial MM01 were analysed for factors predicting overall (OAS) and tumour related survival (TRS). Response to primary induction chemotherapy was relevant for prognosis if a limit of 25% tumour cell mass (TCM) reduction was used to separate responders from non-responders. Furthermore, TCM, histological grading of myeloma cells, degree of bone marrow infiltration, haemoglobin, platelet counts, calcium, creatinine, albumin, beta 2M, and Bence Jones proteinuria correlated to both OAS and TRS. Age was relevant for OAS only. The multivariate analysis revealed histological grading, TCM and platelets as the most reliable prognostic factors. Based on these data the Durie/Salmon classification could be improved by defining poor prognosis patients (50% TRS: 16 months) characterised by pretreatment platelets of < or = 150,000 and/or poorly differentiated myeloma cell morphology. Patients lacking both risk factors displayed 50% survival times of 46 months in stage III and 88 months in stage II. PMID- 8499153 TI - Phase I and pharmacokinetic study of brequinar (DUP 785; NSC 368390) in cancer patients. AB - Brequinar (DUP 785, NSC 368390) is a 4-quinoline carboxylic acid derivative with broad spectrum antitumour activity in experimental models that acts as an antimetabolite by specific inhibition of de novo pyrimidine synthesis. We performed a phase I study of brequinar administered as a 10 min intravenous (i.v.) infusion for 5 consecutive days, every 4 weeks. 67 evaluable patients were entered in this study and a total of 130 courses were administered at doses ranging from 2 to 350 mg/m2. The dose-limiting toxicity was myelosuppression with predominant thrombocytopenia. Myelosuppression was dose-related and non cumulative, with considerable interpatient variability depending on haematological risk factors. The maximum tolerated dose of brequinar was 210 mg/m2/day in poor risk patients whereas patients with good risk haematological profile tolerated higher doses (up to 350 mg/m2/day). Other non-limiting toxicities included nausea and vomiting, mucositis and skin reactions. Brequinar plasma pharmacokinetic profiles were biphasic with alpha half-life ranging from 0.1 to 0.7 h, and beta half-life ranging from 1.5 to 8.2 h. Increase in brequinar area under the plasma concentration versus time curves (AUC) was nonlinear. Day 5 brequinar pharmacokinetics obtained in 21 patients indicated a significant increase in AUC (47%) and half-life beta (133%) compared to day 1 pharmacokinetics in the same patient. Brequinar plasma AUC and the per cent change in platelet count at nadir were correlated (P < 0.001). Although no objective response was observed in this study, one minor response was noted in cervical lymph nodes of a Hodgkin's disease patient. PMID- 8499154 TI - Hormonal therapy for metastatic renal cell carcinoma combined androgen and provera followed by high dose tamoxifen. AB - The purpose of this phase II study was to determine the effectiveness of hormonal therapy with combined high dose androgen and provera or tamoxifen in patients with advanced renal cell carcinoma. 30 patients with metastatic renal cell carcinoma received testosterone propionate 100 mg intramuscularly (i.m.) 5 times weekly plus provera 400 mg (i.m.) twice weekly until disease progression developed. 20 patients, most of whom had previously failed to respond to androgen and provera, received tamoxifen 100 mg/m2 daily. Of the 30 patients treated with androgen and provera, 3 (10%) developed partial responses of brief duration. 2 of 20 patients (10%) experienced tumour response with tamoxifen, one instance of complete disappearance of pulmonary metastases in a patient whose primary tumour was questionably persistent at post mortem and another case demonstrating disease stability. Combined hormonal therapy offers very little therapeutic advantage in advanced renal cell carcinoma. Tamoxifen, in high dose, exerts anti-tumour effects in a small cohort of cases. PMID- 8499155 TI - [Professional strength creates enthusiasm and growth. Interview by Siv Barstad]. PMID- 8499156 TI - [6500 students are without school health services. Interview by Erik Larsen]. PMID- 8499157 TI - [Why should nurses lead their own profession?]. PMID- 8499158 TI - [ISV (Institute for Nursing Science) together with physicians]. PMID- 8499159 TI - [Operating room gets emergency help. Interview by Marit Fonn]. PMID- 8499160 TI - [Give patients identity. Interview by Siv Barstad]. PMID- 8499161 TI - [Nursing under a different sky: Greece]. PMID- 8499162 TI - [St. Lucia: safe sex instead of abstinence]. PMID- 8499163 TI - [Nursing assistants, inspite of unemployment, stick to being nurses]. PMID- 8499164 TI - [Electroshock--witchcraft or wrong treatment?]. PMID- 8499165 TI - [Watching the watchers. Interview by Bjorn Arild Ostby]. PMID- 8499166 TI - [Student guidance: KS (Community Centreal Organization) aims for labor rights. Interview by Kjell Arne Bakke]. PMID- 8499167 TI - [Alarming number of "English disease" among immigrant children. Interview by Ingrid S Stephensen]. PMID- 8499168 TI - [Nursing under a different sky: Ecuador]. PMID- 8499169 TI - [Latvians on a Norwegian tour]. PMID- 8499170 TI - [The next baby will be called Angerlartoq]. PMID- 8499171 TI - [Responsible but not free of failure]. PMID- 8499172 TI - [Women-unfriendly employers]. PMID- 8499173 TI - [A year of their lives. Interview by Bjorn Arild Ostby]. PMID- 8499174 TI - [Nursing in barn odors. Interview by Marit Fonn]. PMID- 8499176 TI - [Nursing under a different sky: Lesotho]. PMID- 8499175 TI - [Nurse in the storm. Interview by Bodil M Skarseth]. PMID- 8499177 TI - [Violated women get help. Interview by Marit Fonn]. PMID- 8499178 TI - [Safe childbirth as a goal. Joint responsibility for the woman in labor]. PMID- 8499179 TI - [Safe childbirth as a goal. The worst conceivable seldom happens. Interview by Bjorn Arild Ostby]. PMID- 8499180 TI - [Safe childbirth as a goal. Midwives at a course]. PMID- 8499181 TI - [Home services are insufficient]. PMID- 8499182 TI - [Women's world]. PMID- 8499183 TI - [French nurses ready for new fight. Interview by Kjell Arne Bakke]. PMID- 8499184 TI - [Nursing under a different sky: Besham]. PMID- 8499185 TI - [Employed via personnel bank. Interview by Bjorn Arild Ostby]. PMID- 8499186 TI - [Limiting access to drugs]. PMID- 8499187 TI - [AIDS in Tanzania]. PMID- 8499188 TI - The Family and Medical Leave Act of 1993: an overview. PMID- 8499189 TI - Nurse-physician collaboration: the time is now! PMID- 8499190 TI - Leadership action: nurse executives share their first-class ideas. PMID- 8499191 TI - Creating partnerships: transforming the physician-nurse executive relationship. PMID- 8499193 TI - Time, time, time--the secret to physician involvement in CQI. PMID- 8499192 TI - Reflections on collaboration: an interview with Mary Doherty. PMID- 8499194 TI - Extradural abscess after central neural block. PMID- 8499195 TI - Closed-loop feedback controlled administration of alfentanil during alfentanil nitrous oxide anaesthesia. AB - We have studied the automatic administration of alfentanil during alfentanil nitrous oxide anaesthesia in 11 patients using a closed-loop feedback control system based on EEG analysis. We chose a median EEG frequency of 2-4 Hz as the EEG set point. The slope of the asymptote to the cumulative dose requirement was used to define an effective therapeutic infusion of alfentanil. Median EEG frequency (mean (SD)) during the feedback period was 3.03 (0.45) Hz. The average effective therapeutic infusion of alfentanil was 0.140 (0.032) mg min-1. We conclude that EEG feedback control may be useful in assessing and defining the dose requirements of alfentanil. PMID- 8499196 TI - Comparison of the effect of EMLA cream, subcutaneous ring anaesthesia and a double cuff technique in the prevention of tourniquet pain. AB - We have examined the effect of EMLA on tourniquet pain and compared it with those of subcutaneous ring anaesthesia (SRA), a double cuff technique and a single cuff (control) during i.v. regional anaesthesia. The durations of analgesia (mean 57.3 (SD 16.6) min) and tolerance (72.3 (13.9) min) to tourniquet inflation in the EMLA group were comparable to those in the SRA group (54.1 (16.2) min and 68.3 (19.0) min), but significantly (P < 0.05) greater than those in the control group (30.0 (10.7) min and 45.6 (14.0) min). The double cuff technique was the most effective method, with 91.5 (14.9) min duration of analgesia. We conclude that EMLA provided a significant analgesic effect on tourniquet pain compared with the control group, but a relatively limited analgesic effect compared with a double cuff technique. PMID- 8499197 TI - Comparison of in vitro contracture testing with ryanodine, halothane and caffeine in malignant hyperthermia and other neuromuscular disorders. AB - In vitro exposure of living skeletal muscle to ryanodine has been proposed as a potentially specific test for malignant hyperthermia (MH). In this study we have compared in vitro contracture responses to halothane, caffeine and ryanodine in skeletal muscle specimens obtained from 155 patients attending for diagnosis of susceptibility of MH and also from six patients having muscle biopsy for diagnosis of other neuromuscular disorders. Although the ryanodine contracture test was not specific for MH, the results suggest it may greatly aid (in conjunction with the standard halothane and caffeine contracture tests) the accurate phenotyping of individuals that is essential for the further genetic analysis of MH. PMID- 8499198 TI - Prejunctional action of neostigmine on mouse neuromuscular preparations. AB - We have studied the effects of neostigmine on the mouse diaphragm and triangularis sterni isolated nerve-muscle preparations. Mechanical responses of the muscle, end-plate potentials and miniature end-plate potentials, and extracellularly recorded nerve ending currents were recorded. In the mouse diaphragm nerve-muscle preparations, neostigmine 1 mumol litre-1 continued to produce some antagonism of tubocurarine-induced block after cholinesterase had been inactivated completely by diisopropyl fluorophosphate 22 mumol litre-1. In the mouse triangularis sterni preparation, neostigmine 0.1-1 mumol litre-1 increased the quantal content of the end-plate potential in a concentration dependent manner. This effect appeared to be sufficient to account for the cholinesterase-independent antagonistic action to tubocurarine under the conditions of the experiments. Neostigmine 1-100 mumol litre-1 depressed the amplitude of the K+ currents of the perineural waveforms in a concentration dependent manner, and this may account for its ability to increase the quantal content of the end-plate potential. Although inhibition of acetyl-cholinesterase is the main mechanism of action of neostigmine, the drug also exerts an additional direct action on motor nerve endings to block the delayed rectifier K+ channels and enhance transmitter release. This effect occurred at clinically relevant concentrations of neostigmine. Physostigmine and pyridostigmine did not possess this additional action. PMID- 8499199 TI - An alternative method of increasing PCO2 using apnoea and continuous positive airway pressure. AB - We have examined the use of continuous positive airway pressure (CPAP) and apnoeic oxygenation for restoration of spontaneous breathing at the end of anaesthesia after controlled ventilation. We studied 45 adult patients without a history of acute or chronic respiratory disturbances. Anaesthesia was induced with thiopentone or propofol and maintained with nitrous oxide and enflurane in oxygen. The patients were normocapnic during artificial ventilation. At the end of surgery, the lungs were ventilated for 5 min with oxygen and then given a CPAP of 8 cm H2O. Spontaneous ventilation was regained after a mean of 5 min and an arterial blood sample was obtained at the third breath. All patients were well oxygenated (PO2 mean 43.5 kPa, range 21-76 kPa) when spontaneous ventilation started. The pH was close to 7.28 in most cases (mean 7.28, range 7.21-7.32), and PCO2 varied in the range 6.6-9.9 kPa (mean 7.9 kPa). It is concluded that the method is safe with regard to oxygenation and acid-base balance. PMID- 8499200 TI - Ventilatory effects of morphine, pethidine and methadone in children. AB - The ventilatory effects of single i.v. doses of morphine 0.1 mg kg-1, pethidine 0.67 mg kg-1 and methadone 0.1 mg kg-1 were compared after ophthalmic surgery in an open, randomized study in 30 children aged 3-8 yr. Ventilatory changes after each drug had distinctive profiles, with appreciable individual variation. Acutely, the decrease in ventilatory frequency was greater with pethidine and methadone than with morphine. The acute decrease in oxygen saturation was greater with methadone and pethidine than with morphine. Methadone produced a greater and longer lasting increase in end-tidal carbon dioxide and greater decrease in end tidal oxygen than morphine or pethidine. Changes in end-tidal carbon dioxide and oxygen concentrations and saturation were most transient after pethidine and of longest duration after methadone. No child developed apnoea or hypoventilation requiring assistance. PMID- 8499201 TI - Comparison of midazolam with propofol for sedation in outpatient bronchoscopy. AB - We have compared sedation for fibreoptic bronchoscopy provided by incremental doses of midazolam with that provided by a computer-controlled infusion of propofol. These two methods were compared in terms of operator and patient acceptability, anxiolysis, effects on systolic arterial pressure and oxygen saturation. Tests were made also of memory and motor reactions, before and 60 min after the end of the procedure. Acceptability to operators and patients was high in both groups. There were no significant differences between the groups in systemic arterial pressure or anxiolysis. Oxygen saturation decreased in both groups (propofol group median 83% (range 69-95%); midazolam group median 86% (range 77-95%)) (ns). The median recovery time was 5 min (range 5-10 min) in the propofol group and 10 min (range 5-40 min) in the midazolam group (P < 0.01). Memory and motor reaction times 60 min after the end of the procedure did not differ from baseline in the propofol group, but were significantly impaired in the midazolam group. PMID- 8499202 TI - Comparison of infusion rates of three i.v. anaesthetic agents for induction in elderly patients. AB - We have compared the effect of different rates of injection of 2.5% thiopentone, 0.5% methohexitone and 0.2% etomidate for induction of anaesthesia in 90 premedicated, elderly patients. The agents were administered by infusion pump at rates of 1200 ml h-1, 600 ml h-1 and 300 ml h-1, respectively until anaesthesia was induced as judged by loss of verbal contact with the patient. The times for induction were significantly greater with the slower infusion rates (thiopentone 41 s, 57 s and 91 s (P < 0.001); methohexitone 44 s, 62 s and 84 s (P < 0.01); etomidate 48 s, 59 s and 87 s (P < 0.001)). The doses were significantly smaller (P < 0.001) with the slower infusion rates for all three agents (thiopentone 5.0, 3.7 and 2.8 mg kg-1; methohexitone 1.00, 0.75 and 0.56 mg kg-1; etomidate 0.26, 0.15 and 0.11 mg kg-1). For each drug there was no significant difference in induction characteristics, oxygen saturation, heart rate or mean arterial pressure, at the different infusion rates. PMID- 8499203 TI - Haemodynamic changes produced by inhalation anaesthetics in the presence of phosphodiesterase inhibition. AB - We have investigated the circulatory effects of halothane and isoflurane in the presence of the phosphodiesterase inhibitor, enoximone, in 20 patients, ASA class III, aged 40-70 yr, undergoing coronary artery bypass grafting. After induction of anaesthesia (midazolam, fentanyl, etomidate and pancuronium) all patients received enoximone 0.5 mg kg-1, followed, 10 min later, by either halothane 1 MAC (group I; n = 10) or isoflurane 1 MAC (group II; n = 10). Haemodynamic variables were measured and blood samples (arterial and mixed venous) were obtained before (control, t0), 5 (t1) and 10 (t2) min after the injection of enoximone and immediately (t3) and 5 (t4) min after steady state conditions with halothane or isoflurane, as verified by the end-expiratory concentration. Heart rate, mean arterial pressure (MAP), mean pulmonary artery pressure, pulmonary capillary wedge pressure and right atrial pressure were recorded. Cardiac (CI) and stroke volume indices, systemic (SVR) and pulmonary vascular resistance, oxygen availability (QO2), oxygen consumption and oxygen extraction rate were calculated using standard formulae. MAP decreased significantly in both groups after bolus injection of enoximone (group I: 11%; group II: 7%). Under steady state conditions with the volatile anaesthetics, a further significant decrease in MAP was observed (group I: 12%; group II: 12%). Enoximone produced a significant increase in CI (group I: 25%; group II: 27% compared with control). After administration of isoflurane, CI remained essentially unchanged, while halothane decreased CI significantly by 20%. In both groups, SVR decreased significantly after administration of enoximone (group I: 26%; group II: 24%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499204 TI - The value of pre-emptive analgesia in the treatment of postoperative pain. PMID- 8499205 TI - Comparison of nasal cannulae with face mask for oxygen administration to postoperative patients. AB - Thirty postoperative patients were allocated randomly to receive oxygen by Hudson face mask at 4 litre min-1 (group I) or 2 litre min-1 (group II) via nasal cannulae. From 22:00 on the first night after operation, the position of the nasal cannula or face mask was observed for 8 h using video and oxyhaemoglobin saturation (SpO2) recorded simultaneously. In group I the mask remained on and positioned correctly in five patients. In the 10 other patients it was removed a total of 28 times, 17 for nursing tasks, for a median time of 2 min 39 s (range 30 s to 7 h 40 min 40 s). In group II the nasal cannula was removed once in one patient for 16 min 38 s and eight times in another for a total of 1 h 18 min 7 s. Average SpO2 with mask on was 98% (range 96.1-99.9%), with mask off 95% (range 89.8-98.8%) and with cannula 97% (range 90.8-99.3%). We conclude that nasal cannulae are more likely to remain in position than face masks and maintain an adequate saturation in most patients. PMID- 8499206 TI - Relationship between volume of distribution of atracurium and body weight. AB - We have determined the central and steady state volumes of distribution of atracurium 0.25 mg kg-1 in 41 healthy adult patients. Volume of distribution, corrected for body weight (ml kg-1); correlated negatively with body weight (r = 0.612 for central volume of distribution; r = -0.737 for the steady state volume of distribution). When expressed as an absolute volume, neither central nor steady state volume of distribution correlated significantly with body weight (r = 0.120 and r = 0.131, respectively). These data cast doubt upon the necessity for the dose of atracurium to be related to body weight in the healthy adult population. PMID- 8499207 TI - Effect of radiant heat on the metabolic cost of postoperative shivering. AB - Hypothermia and postoperative shivering are uncomfortable and may be dangerous. This study demonstrates that postoperative shivering may be controlled quickly and effectively with radiant heat, thereby reducing oxygen consumption and increasing thermal comfort. PMID- 8499208 TI - Metabolic effects of propofol and flunitrazepam given for sedation after aortic surgery. AB - Sixteen patients who had undergone abdominal aortic surgery were allocated randomly to receive either propofol (total dose 3.2 (SEM 0.3) mg kg-1 h-1) or flunitrazepam (total dose 15 (2) micrograms kg-1 h-1) for 16 h after operation. Metabolic effects of sedation were assessed using a Deltatrac metabolic monitor. Initiation of sedation induced a 25% decrease in VO2 in both groups. The decrease was about 40% at 16 h. VO2 increased within 30 min after discontinuation of propofol and stabilized at values considerably less than the immediate postoperative value. A similar but slower increase was noted with flunitrazepam. While the propofol loading dose reduced the Buffington index and should therefore be avoided, no cardiovascular side effects were noted with the maintenance infusion. Weaning from ventilatory support was achieved within 15 (2) min and 264 (108) min after discontinuation of propofol and flunitrazepam, respectively. PMID- 8499209 TI - Hepatic elimination of diazepam: interactions with albumin, desflurane and sevoflurane. AB - We have studied the effect of sevoflurane and desflurane on the hepatic elimination of diazepam, by incubating slices of rat livers in a closed system. Protein free and protein containing (albumin 10 g litre-1) buffers were used to examine the effect of the anaesthetics on enzyme activity and diazepam binding to albumin. Both anaesthetics (in concentrations of 0.5, 1.5 and 3.0 mmol litre-1) reduced the elimination of diazepam slightly in the absence of albumin, while the presence of the protein increased elimination to a maximum of 30% at the greatest concentration of the anaesthetics. These data support previous observations that volatile anaesthetics may interact pharmacokinetically with both liver enzyme activity and drug binding to albumin. PMID- 8499210 TI - Anaesthetic properties of dimethylthiourea. AB - We have examined dimethylthiourea, a potent scavenger of free radicals, for its anaesthetic properties in mice and rats. In mice, dimethylthiourea abolished the righting reflex at intraperitoneal doses greater than 1.5 mg g-1 bodyweight; in rats, it decreased the MAC value for isoflurane in a dose-dependent fashion. Dimethylthiourea 0.5 g kg-1 decreased isoflurane MAC by 23%; at a dose of 2.0-4.0 g kg-1, it abolished the response to tail clamp. Doses of 4.0 g kg-1 were lethal in the presence of isoflurane. A serum concentration of dimethylthiourea approximately 1 mg ml-1 produced a 50% reduction in isoflurane MAC. These anaesthetic properties of dimethylthiourea may influence experimental studies that examine the biochemical and physiological properties of this agent. PMID- 8499211 TI - Spontaneous excitatory movements during recovery from propofol anaesthesia in an infant: EEG evaluation. AB - Spontaneous excitatory movements have been observed during recovery from propofol anaesthesia in children. Epilepsy has been postulated as a possible mechanism to explain these movements. We report the first case in which these spontaneous excitatory movements were studied using simultaneous multichannel EEG recordings. PMID- 8499212 TI - A continuous subdural block. AB - We describe a case of accidental subdural block, after attempted extradural puncture for Caesarean section. Fractionation of the local anaesthetic dose led to avoidance of more serious complications. Subdural fentanyl and a continuous low-dose subdural infusion were used satisfactorily for intraoperative management and postoperative analgesia. As little as 0.5 ml of bupivacaine, hourly, provided satisfactory analgesia over a 15-h period. PMID- 8499213 TI - Possible venous air embolism with a new water jet dissector. PMID- 8499214 TI - Fresh gas requirements of an enclosed afferent reservoir breathing system in anaesthetized, spontaneously breathing adults. AB - Using two methods of determining the onset of rebreathing, we have determined the minimum fresh gas flow rate (VF) of the Ohmeda enclosed afferent reservoir breathing system (EAR) in anaesthetized, spontaneously breathing adults. Rebreathing as defined by the Kain and Nunn criteria did not occur when the VF/VE ratio was greater than 0.70. A mathematical model was used to calculate the degree of rebreathing at each VF. From this model, rebreathing did not occur when VF was 0.86 VE or more and this value of VF/VE is considered appropriate to eliminate rebreathing in clinical practice. PMID- 8499215 TI - Spinal extradural abscess: pursuit of vigilance. AB - A case of delayed extradural abscess and quadriplegia after extradural steroids is presented. Nine other cases of extradural abscess from the literature are reviewed to illustrate the influence of continuity of hospital admission and informed surveillance on successful outcome when extradural infection arises after extradural medication. A Medic-Alert system is proposed as a means of improving vigilance and neurological outcome for patients at risk. Careful study of the cost-effectiveness of such a scheme is recommended. PMID- 8499216 TI - Lumbovertebral syndrome after extradural blood patch. PMID- 8499217 TI - Intermittent vs continuous extradural infusion of bupivacaine during labour. PMID- 8499218 TI - Does etomidate cause haemolysis? PMID- 8499219 TI - Transthoracic endoscopic sympathectomy. PMID- 8499220 TI - Transthoracic endoscopic sympathectomy. PMID- 8499221 TI - Pre-emptive extradural analgesia. PMID- 8499222 TI - Metabolic effects of cholecystectomy. PMID- 8499223 TI - Vip-induced cross-talk between G-proteins in membranes from rat anterior pituitary cells. AB - In order to study the activation mechanism of heterotrimeric G-proteins by agonist-liganded receptors, GTP gamma S binding to membranes was measured in rat adenohypophyseal cells after addition of dopamine (DA) or vasoactive intestinal peptide (VIP), which, respectively, inhibit and activate pituitary adenylyl cyclase. G-protein subunit present in anterior pituitary cells was characterized by either ADP-ribosylation catalysed by Bordetella pertussis and cholera toxins or by immunoblot using specific antisera. Binding of GTP gamma S was found to depend upon GTP gamma S and Mg2+ concentrations; it was sensitive to pretreatment of the cells with cholera and Bordetella pertussis toxins (IAP). DA increased binding of the nucleotide. Paradoxically, VIP decreased the rate of GTP gamma S binding; the effect was suppressed by prior treatment of the cells with either cholera toxin or IAP. VIP also increased [33P]ADPribose incorporation in Gi/Go proteins catalysed by IAP. Forskolin was also able to decrease GTP gamma S binding, thus suggesting that the binding of forskolin with the adenylyl cyclase catalytic unit might activate Gs proteins through an increased interaction between Gs and adenylyl cyclase. Taken together, these results suggest that VIP, as well as forskolin, may both accelerate the activation of Gs and suppress the inhibitory effect of activated Gi/Go-proteins. Interactions between Gs and Gi/Go subunits mediated by beta gamma and/or adenylyl cyclase might thus result in a kinetic coupling of transduction pathways involving distinct G-proteins. PMID- 8499224 TI - Altered cellular signalling and decreased platelet sensitivity to adenosine in insulin-dependent diabetic patients with proliferative retinopathy. AB - Platelets from patients with insulin-dependent diabetes with proliferative retinopathy showed the same reactivity to ADP as those from control subjects. Responsiveness of platelets to the aggregation inhibitor adenosine and to the analogue N-ethylcarboxamidoadenosine was decreased in diabetes. In contrast, responsiveness to the anti-aggregatory effects of prostaglandin I2 was not significantly altered in diabetes. Platelets from diabetic patients exhibited decreased formation of cyclic AMP in response to N-ethylcarboxamidoadenosine compared with those from control subjects. In contrast, when adenylyl cyclase was stimulated by prostaglandin I2 or by forskolin, no differences in cyclic AMP formation were observed between control and diabetic platelets. Diabetes was associated with an apparent loss of high-affinity binding of [3H]N ethylcarboxamidoadenosine to platelet membranes. Possible mechanisms that could contribute to this diabetes-induced change in signalling through the platelet A2 adenosine receptor are discussed. PMID- 8499225 TI - Fc epsilon RI and the T cell receptor for antigen activate similar signalling pathways in T cell-RBL cell hybrids. AB - In order to investigate the functional similarities of the high affinity receptor for IgE (Fc epsilon RI) and the T cell receptor for antigen, we have developed a high efficiency polyethylene glycol-mediated fusion method to make somatic hybrids between cells from a mast cell line (RBL-2H3) and cells from T lymphoma cell lines (Jurkat and HPB-ALL). Using flow cytometry to select for the heterologously fused cells, we demonstrated that aggregation of the T cell receptor results in the efficient secretion of [3H]5-hydroxytryptamine from RBL cell-derived granules. In addition, both receptors mediate Ca2+ mobilization in the hybrid cells that is insensitive to inhibition by the protein kinase C activator phorbol-12-myristoyl-13-acetate (PMA). In contrast, Ca2+ mobilization caused by aggregation of Fc epsilon RI in the parent RBL cells is completely inhibited by PMA. The results indicate that these two different receptors for foreign antigen can substitute for each other to trigger responses in the hybrid cells that are unique to each cell type. The methodology employed has general utility for studying signal transduction mediated by mammalian cell surface receptors. PMID- 8499226 TI - Pertussis toxin expression in Drosophila alters the visual response and blocks eating behaviour. AB - Pertussis toxin inactivates certain G-proteins by introducing an ADP-ribose group near the carboxyl-terminus of the alpha-subunit. The major pertussis toxin substrate in Drosophila tissues is Go alpha. We introduced a pertussis toxin gene under control of the hsp70 heat-shock promoter into the Drosophila genome. When heat-shocked, transformed flies produce active pertussis toxin which ADP ribosylates endogenous Go alpha. Pertussis toxin is expressed in photoreceptors, in the lamina of the eye and in epithelial cells lining the gut. As expected from the absence of Go alpha in photoreceptors, pertussis toxin does not affect the photoreceptor component of the Drosophila visual response. However, it abolishes light on- and off-transients in the electroretinogram. These transients normally arise from the lamina, a tissue where Go alpha transcripts have been detected. Pertussis toxin expression also blocks embryonic development and shortens the lifetime of adult Drosophila. Following heat-shock, transformed adults are active, but they fail to take up nutrients because they stop eating. High energy metabolites are significantly depleted shortly after pertussis toxin expression is induced and the flies die within 48 h. PMID- 8499227 TI - A role for inositol-glycan mediators and G-proteins in insulin action. PMID- 8499228 TI - [Productivity and teaching]. PMID- 8499229 TI - [Gastroschisis: study of teratogenic factors]. AB - The medical and surgical treatment of gastroschisis has improved in the last decades leading to better survival rates. Since in our institution there were the same cyclic variations in the incidence as in other large series in the literature, we have reviewed the epidemiological factors that can be at the origin of such variations. We studied 20 different variables in our patients in a case-control basis. Only five of them were significantly different between cases and controls. (Birth weight, gestational age, infection, drugs during the first three months of gestation and maternal age). The results point to the role of environmental factors more relevant in the etiology of gastroschisis than genetic ones. PMID- 8499230 TI - [Digestive irrigation, new perspectives]. AB - The hydroelectric and pH alterations that produce the digestive irrigation previous to the surgery, have justified the fulfillment of this study, addressed to design a kind of solution to be used at pediatric patients. It has been used two solutions: one of them proposed by Davis (S_I), and the other (S_II), is Davis' solution modification, in which it is decreased the quantity of polyethylene glycol (PEG-4000) and it is increased the concentration of bicarbonate. The analysis of the results demonstrated the superiority of the second solution avoiding the tendency to the acidosis that show the Davis' solution. PMID- 8499231 TI - [Alkaline gastroesophageal reflux. Diagnosis by double-channel pH measurement]. AB - Alkaline gastroesophageal reflux (AGER) has been documented in adult subjects, but few in pediatrics. 24-hours double pH-monitoring was performed in 40 nonrefluxers (control group) and 69 gastroesophageal reflux (RGE) children to quantify AGER. Esophageal phmetric variables were measured at 4 and 7 levels; gastric variables were measured at 4. Forty cases were classified into acid GER, 15 into acid alkaline GER (mixed), 8 into AGER, and 6, with clinical, manometric or endoscopic evidence of GER into "silent" GER. The acid and mixed GER groups had longer periods of acid exposure in esophagus than control, AGER and "silent" GER groups. All groups had long periods of pH > 7 in esophagus. In conclusion, the double gastroesophageal pH monitoring, by verifying the source of alkaline reflux into the esophagus had advantage of better quantifying alkaline reflux over single pH monitoring. AGER might be more frequent in pediatrics than adults. PMID- 8499232 TI - [Helicobacter pylori infection and duodeno-gastric reflux]. AB - We have studied and measured the duodenogastric reflux in 11 children with chronic abdominal pain and Helicobacter pylori (HP) through 24-hours gastric pH metric studies. All parameters evaluated: Number of reflux episodes (NR 92.87 +/- 27.66), number of reflux episodes longer than 5.0 minutes (NR > 5M 11.45 +/- 4.68), longest reflux episode (LR 67.37 +/- 45.57) and alkaline reflux area (AA 604.89 +/- 443.54) had significative differences against a normal group (40 children). We concluded that duodenogastric reflux and HP are frequent together. PMID- 8499233 TI - [Meshed graft fixation with synthetic glue (Nobecutan) in pediatrics]. AB - Burns in children carry many age-related problems. Maintenance of immobility and cleanness of absorbent dressings are very difficult, especially in infancy and large wounds. These problems are very important when meshed skin grafts are used. Graft survival is disturbed by patient movements and septic colonization, especially in the early postoperative period. Over a two years period we have been applying Nobecutan as meshed skin graft fixation procedure, antiseptic and protecting wound coat. The use of Nobecutan is a time-saving technique. No sutures nor staples are employed, which is very important when working with burned children. No local adverse effects, nor prolongation of wound healing had been observed. PMID- 8499234 TI - [Topical treatment with oxybutynin chloride in neurogenic incontinence]. AB - Intravesical oxybutynin chloride was administered to 12 children with neurogenic bladder and incontinence who had unacceptable side effects. Urodynamic studies showed hyperreflexia was eliminated or improvement in 100% of them and low compliance was improved (88%), with a mean increase in bladder volume to 123% and a mean decrease of filling pressure to 24 cm H2O. Six patients became completely dry (50%), 4 continent period was increased and 2 did not improve. No systemic effects were observed. PMID- 8499235 TI - [Differentiated thyroid carcinoma in childhood: multicenter review of the club of pediatric oncology]. AB - The club of paediatric oncology of the Sociedad Espanola de Cirugia Pediatria conducted a retrospective and multicentric study on differentiated thyroid carcinoma in children. Seventeen cases from four hospitals were reviewed. Initial surgery in all cases consisted of partial or total thyroidectomy, associated in 76% of cases by cervical node removal. In 6 patients (35%) tumoral mass relapsed and 13 cases (76%) hypothyroidism was observed as a post-surgical sequela (in one patient, furthermore dysphonia and hypoparathyroidism persisted). Total survival rate in the series is 100%; one patient is currently diagnosed of node relapsed and remaining patients are disease-free. A diagnostic protocol based on echography, gammagraphy and biopsy is proposed. Oncology surgery i.e. tumoral and healthy tissue resection with node removal in one operation is recommended. With this approach, although we tend to place the patient in hypothyroidism and therefore susceptible to substitutive therapy, the multiple relapses observed in the review would be avoided. Prolonged follow-up guarantees early diagnosis of possible tumoral recurrence. PMID- 8499236 TI - [Surface microscopic patterns of an experimental model of surgically induced carcinogenesis]. AB - An experimental model of carcinogenesis is developed by authors, using internal urinary diversion in Wistar rats. Results show the transformation of normal digestive pattern, discovering proliferative-inflammatory changes at the first time which after go to an histiotypical tumorous pattern. They conclude at the carcinogenicity of the presented surgical model and is described the evolution of the superficial morphological pattern during the tumorigenic process. PMID- 8499237 TI - [Isolated congenital stenoses of the extrahepatic bile ducts]. AB - Congenital isolated strictures of the extrahepatic bile ducts are very rare, with only eleven cases reported until 1990. We report two infants (3 and 2 months old, respectively) one of them with a choledocal stenosis and the other with a congenital stricture of the common hepatic duct and spontaneous perforation of the biliary tract. Dilatation of the distal stricture with insertion of T-tube was performed during surgical act. We get success with this technique in both cases. PMID- 8499238 TI - [Acute gastric volvulus in a patient with asplenic syndrome]. AB - A 18 month-old boy with asplenic syndrome was admitted to our hospital with a twelve hours history of mucous vomiting, abdominal pain and a round epigastric mass. It was diagnosed as having a gastric volvulus and an emergency laparotomy was performed. The stomach was situated at the right side and a mesenterioaxial volvulus was found, with cyanosis of the antrum. The gastrophrenic and gastrosplenic ligaments were absent. The clinical and radiological characteristics of asplenic syndrome are reviewed. The pediatric surgeons must be aware of the digestive malformations of the asplenic syndrome, because some of that like malfixation of the stomach could be the cause of an acute abdomen. PMID- 8499239 TI - [Acute abdomen of unusual cause in children]. AB - The acute abdomen in childhood is in most cases caused by an acute appendicitis and rarely it is secondary to other diseases. It is for that reason, that we present two cases extremely rare of acute abdomen: the first one was an abdominal Actinomycosis secondary to acute appendicitis that looked like a tumor and the second that was an acute omentitis due to pinworms. PMID- 8499240 TI - [7 years' experience with hepatic transplantation in children]. AB - Between the 7th of June 1985 and december 1991, 71 liver transplants (LTx) were performed in 60 patients (pts) with ages ranging from 8 months to 14 years and weight between 4 and 38 kg. Sixty-two percent were cholestatic diseases (32 biliary atresia, 3 sclerosing cholangitis and 2 biliary paucity), 25% metabolic hepatic-based diseases (6 glycogen storage disease, 4 Byler disease, 3 tyrosinaemia and 2 alpha-1-antitrypsin deficiency) and 13% miscellaneous diagnosis (2 post-hepatitic cirrhosis, 2 autoimmune hepatitis, 2 fulminant hepatitis and one case of cholesteryl ester storage disease and one case of Budd Chiari disease). Primary non-function was observed in 4 cases (5.5), severe bacterial infection in 4 pts. (5.5%), severe viral infection in 2 (3%), arterial thrombosis in 2 (3%), arterial rupture in 1 (1.5%), recurrence in 3 cases (5%) and chronic rejection in two (3%). Two patients were in III and IV coma respectively prior to surgery. Intraoperative mortality was nil. Total mortality was 19 cases, which represents an actuarial survival rate of 70%. Our philosophy has always been to offer this treatment to all patients candidates for LTx. In some end-stage situation it is very difficult to objectively assess their possibilities and when necessary refuse the only opportunity the patient has. Nevertheless, results are satisfactory. IN CONCLUSION: 1. LTx in children has been confirmed in our programme over 7 years as efficient treatment for end-stage liver diseases. 2. Advances in the therapeutic arsenal and increased experience have notably improved the progress of these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499241 TI - Effect of acute and chronic hyponatremia on blood-brain barrier function in the rat. AB - To study whether acute or chronic hyponatremia alters blood-brain barrier (BBB) permeability, rats made hyponatremic by constant desmopressin acetate infusion were studied by NMR spectroscopy and imaging. On constant volume ventilation and nitrous oxide, acute (1- and 2-day) and chronic (7- and 14-day) hyponatremic and normonatremic controls were infused with 0.25 M HCl. Despite reducing blood pH by at least 0.35 in < 50 min, brain pH, measured by 31P NMR, was unaffected in any group. As a second test of BBB function, gadolinium-DTPA (Gd-DTPA) was injected intravenously in these five groups. Coronal slice 1H NMR images obtained before and after Gd-DTPA showed image intensity changes in multiple areas outside brain, but neither control nor hyponatremic rats showed any differences in cortex, white matter or cerebellum. To ascertain whether the threshold for BBB disruption was altered, hypertonic mannitol (1.5, 2.0 or 3.0 mL) was injected rapidly into one internal carotid artery and pre- and post-Gd-DTPA images obtained. In both control and hyponatremic rats only the largest dose caused detectable Gd-DTPA leakage into brain. Thus, BBB function appears intact in both acute and chronic hyponatremia since neither H+ nor GD-DTPA penetrated the barrier and resistance to mannitol disruption was unaffected by hyponatremia. PMID- 8499242 TI - Bulk magnetic susceptibility induced broadening in the 19F NMR of suspended leukemic cells. AB - The relevance of bulk magnetic susceptibility (BMS) induced broadening to in vivo NMR studies of intact cells has been examined and the significance of the contribution of BMS difference to the resolution of intra- and extracellular resonances was demonstrated. BMS difference between intra- and extracellular compartments was found to limit the resolution of intra- and extracellular 19F resonances of fluoro compounds in leukemic cells. PMID- 8499243 TI - Non-linear regression and variance ratio analysis of time based NMR data. AB - Biomedical NMR experiments rely frequently on data obtained sequentially over time. A method is presented for analysis of time based NMR data, which allows modelling of continuous and discontinuous functions to observed intensity changes by non-linear regression and which uses variance ratio analysis to compare these models statistically. The method eliminates many of the usual problems in the parametric analysis of experimental values obtained at discrete time points and of comparison of the coefficients of model functions which require unsubstantiated assumptions about the distribution of parameters and ignore internal correlations which may exist between such parameters. The variance ratio method is illustrated for multiple time courses obtained with 23Na NMR of perfused rat kidney undergoing hypoxic perturbation in the presence of different treatments. PMID- 8499244 TI - Transmembrane 19F NMR chemical shift difference of fluorinated solutes in liposomes, erythrocytes and erythrocyte ghosts. AB - In erythrocytes suspended in isotonic medium, a number of fluorinated anions showed well resolved 19F NMR resonances from the solute populations in the intra- and extracellular compartments; the intracellular resonances were shifted to higher frequency (low field). In addition 19F NMR resonances of extracellular solutes were shifted to higher frequency when bovine serum albumin was incorporated into the extracellular medium. The dependence of 19F NMR chemical shift on protein concentration was also demonstrated using resealed red cell ghosts and liposomes; in the presence of external hemoglobin, lysozyme and bovine serum albumin, the shift of the external resonances was to higher frequency. In addition, significant high frequency shifts of 19F NMR resonances were evident along with an increase of temperature. The results of the present study further support the contention that the principal physical basis for the shifts is the disruption of direct hydrogen bonds between 19F of the solutes and (primarily) solvent H2O by protein hydration. The 'split peak' phenomenon is of general importance in biological systems where a transmembrane protein-concentration difference exists. PMID- 8499245 TI - Simultaneous 31P NMR spectroscopy and laser Doppler flowmetry of rat brain during global ischemia and reperfusion. AB - The relationship between blood flow and metabolism was studied in halothane anaesthetized, normothermic rats submitted to 30 min global ischemia by four vessel occlusion. Phosphocreatine (PCr), ATP, intracellular pH and intracellular magnesium (pMg) were measured by 31P NMR spectroscopy, and blood flow by laser Doppler flowmetry. Prior to ischemia the PCr/ATP ratio of fully relaxed spectra was 2.4 +/- 0.3, intracellular pH was 7.26 +/- 0.15 and pMg was 3.26 +/- 0.13. Vascular occlusion led to complete cessation of blood flow in four out of eight rats, and to incomplete ischaemia (< 10% of control) in the other four animals. During vascular occlusion EEG flattened and energy metabolism broke down in all but one animal with a residual blood flow of 8% of control. pH declined to 6.70 +/- 0.08. The speed of electrophysiological and metabolic recovery after 30 min ischemia varied considerably from animal to animal. Variability depended mainly on the recirculation delay (i.e., the interval from vascular release to normalization of blood flow) but was independent of residual blood flow during ischemia, pre-ischemic glucose, ischemic or post-ischemic acidosis, or the degree of post-ischemic hypoperfusion. After 3 h recirculation PCr and intracellular pH returned to normal but pMg was slightly increased, and ATP was reduced by up to 50% in all animals except the rat with incomplete breakdown of energy metabolism during ischemia. The dissociation between PCr and ATP is attributed to a loss of total adenylate, the severity of which depends on the quality of post-ischemic recirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499246 TI - Biological applications for small solenoids: NMR spectroscopy of microliter volumes at high fields. AB - In this paper we describe features of an NMR probe designed for the study of small, superfused muscles. We also present the results of an empirical study of the performance characteristics of several configurations of small solenoid coils, ca 2 mm diameter. Our data show that optimal use of the available volume of sample becomes the prime consideration in coil design at this scale. In contrast to large biological samples, for such small coils the equivalent resistance associated with the sample is minor relative to the resistance of the RF coil itself. Thus, substantial improvements in the S/N ratio can be obtained by adopting coil configurations that are inferior electrically, but which can sample a greater volume of tissue. PMID- 8499247 TI - Effects of fish oil on phospholipid metabolism in human and rat liver studied by 31P NMR spectroscopy in vivo and in vitro. AB - The effect of omega 3 fatty acids on the metabolism of the normal liver was studied using 31P NMR spectroscopy. Human subjects were examined before and after 1, 3 and 7 days of supplementation with 50 mL fish oil per day (12 g omega 3 fatty acids). 31P NMR spectra (1.6 T) revealed a significant increase in phosphodiester (PDE) to ATP ratios after 1 and 3 days of fish oil. After 7 days, [PDE]/[ATP] ratios at a TR of 1 s had returned to baseline levels, but [PDE]/[ATP] at a TR of 5 s appeared to remain high. Rats were fed diets containing 50% of the energy from fish oil or normal rat chow (controls) for 14 days. 31P NMR liver spectra in vivo (4.7 T) confirmed increased [PDE]/[ATP] in rats fed fish oil compared to controls, although the difference was only statistically significant at a TR of 1.5 s but not at a TR of 8 s. 31P NMR spectra of rat liver extracts (8.7 T) suggested that increased concentrations of glycerophosphocholine and possibly glycerophosphoethanolamine were responsible for rising PDE levels in vivo. Phosphocholine (PC) concentrations were markedly reduced in rat liver after fish oil. The combined rise in glycerophosphocholine and reduction in PC would be consistent with a shift from the phospholipase C to the phospholipase A1/A2 pathway of phosphatidylcholine breakdown after fish oil consumption. PMID- 8499249 TI - Community care reforms. A guide to the changes. PMID- 8499248 TI - An in vivo 31P MRS study of patients with liver cirrhosis: progress towards a non invasive assessment of disease severity. AB - Fourteen patients with liver cirrhosis of differing severity participated in a one-dimensional chemical shift imaging 31P MRS study of the liver. Patients were divided into two groups according to the severity of their liver disease using Child's classification and the aminopyrine breath test (AB test). Seven normal volunteers without liver disease acted as controls. The phosphomonester (PME) peak in normal subjects was 4.77% (95% confidence interval, CI: 4.11-5.42) of total phosphorus. The PME peak was significantly elevated in both mild cirrhosis [5.80% (95% CI: 5.46-6.14), p = 0.0051, vs normal subjects] and severe cirrhosis [9.64% (95% CI: 8.71-10.57), p = 0.0002, vs normal subjects and p = 0.001, vs mild cirrhosis]. There was a significant negative linear correlation (r = 0.88, p < 0.01) of PME with the percentage dose of 14CO2 excreted over 2 h in the AB test. pH values in patients with mild cirrhosis [7.45 (95% CI: 7.35-7.55)] but not severe cirrhosis [7.36 (95% CI: 7.25-7.47)] were significantly elevated (p = 0.04) compared to normal subjects [7.29 (95% CI: 7.17-7.41)]. Comparison of the peak area of PME at TR = 0.5 s against that using TR = 5.0 s in cirrhotic liver suggested no reduction in T1 of phosphorus metabolites in cirrhosis. A relationship between the severity of liver cirrhosis and a relative increase in PME was demonstrated and this was not due to a reduction of T1. This study highlights the clinical potential of 31P MRS as a non-invasive means of assessing the severity of liver cirrhosis. PMID- 8499250 TI - Community care reforms. Evolution not revolution. PMID- 8499251 TI - Community care reforms. The good, the bad and the ugly. PMID- 8499252 TI - Community care reforms. Brave new world? PMID- 8499253 TI - Nurses work. Campaign action. PMID- 8499254 TI - Nurses work. Sell your initiative. PMID- 8499255 TI - Nurses work. Practice to make perfect? PMID- 8499256 TI - A framework for wound management. AB - This article looks into four of the most commonly used wound dressing products: Scherisorb (now renamed Intrasite), Kaltostat, Lyofoam and Granuflex. Their characteristics and uses are discussed, and a simple framework for choosing the appropriate dressing for individual wounds has been compiled. The author concludes that there is no 'ideal' dressing which can be used at all the stages of the wound healing process. PMID- 8499257 TI - Sampling in non-experimental research. AB - The importance of choosing an appropriate sample in non-experimental research studies is undisputed, but it is an area which causes problems for researchers from many fields, including nursing. The authors illustrate the decisions which must be made when selecting a sample by considering a hypothetical study of the socialisation of student nurses. PMID- 8499258 TI - Pain control: patient and staff perceptions of PCA. AB - In the United Kingdom, patient controlled analgesia (PCA) has been used primarily as a research tool and its place in the treatment of postoperative pain is only slowly being established. The concept of patients being able to control their own pain relief is therefore new to staff and patients. In this study, a small part of a larger study concerned with the personality characteristics and the effectiveness of PCA which formed the basis of the author's PhD research, 70 patients who had used PCA for postoperative pain relief, and 20 nursing and anaesthetic staff, completed a questionnaire about PCA. The results showed a high level of enthusiasm for PCA among all categories of respondents. PMID- 8499259 TI - It is time to be HIV interrogative. PMID- 8499260 TI - Working parents: maternal damnation. PMID- 8499261 TI - Seeing surgical spirits. PMID- 8499262 TI - Purchasing: commission impossible? PMID- 8499263 TI - Realities of health service rationing. PMID- 8499264 TI - Buying a computer. PMID- 8499265 TI - Community care: a psychiatric case for reform. PMID- 8499266 TI - Patient focused care: ceaseless change. PMID- 8499267 TI - Education: a major milestone. PMID- 8499268 TI - Nursing overseas: caring in a divided community. PMID- 8499270 TI - Nurses work. Help yourself. PMID- 8499269 TI - Nurses work. De-stressing distress. PMID- 8499271 TI - Nurses work. Beat the axe. PMID- 8499272 TI - Using Orem's model in psychiatric nursing. AB - While Orem's model has not been extensively applied to psychiatric nursing, there is some evidence (1, 2) of its use in psychiatric hospital settings in the UK. Anticipating that the concept of self-care may well become more readily incorporated into our changing health care system, this article sets out to examine some key aspects which psychiatric nurses may need to take into account when considering the use of the model in practice. PMID- 8499273 TI - Treating systemic lupus erythematosus. AB - Systemic lupus erythematosus is one of the more common rheumatic complaints, affecting mainly women of child-bearing age. It is a life-threatening condition that affects the immune system and causes damage to the main organs of the body. To coincide with Lupus Awareness Week (10-17 April), this article reviews the symptoms, causes, diagnosis and treatment of systemic lupus erythematosus and examines ways in which research is improving management of the condition. PMID- 8499275 TI - The Standard guide to making sense on paper. PMID- 8499274 TI - NVQ assessment for care assistants. AB - This article discusses the findings of a preliminary investigation into the needs of care assistants undertaking a national vocational qualification (NVQ) in health or social care within a nursing and midwifery college. It is part of a longitudinal study which attempts to determine quality indicators for the structure, process and outcomes of NVQ assessment. Preliminary findings indicate that participants are generally satisfied with the structure and process of their NVQ programme, but some concerns regarding pre-access information, programme documentation, access to tutors and work-place assessors and personal study requirements are raised. These issues are discussed within the general arena of adult education and recommendations for appropriate programme development are made. PMID- 8499276 TI - Childcare: smacking of harsh reality. PMID- 8499277 TI - Unnatural selection. PMID- 8499278 TI - Education needed after AZT failure. PMID- 8499279 TI - 'Blind spot' theory for HIV's damaging power. PMID- 8499280 TI - Bosnia: the suffering goes on. PMID- 8499281 TI - Community care reforms. Balancing the budget. PMID- 8499282 TI - Nurses work. Lost in the community? PMID- 8499283 TI - Nurses work. Stewards work. PMID- 8499284 TI - The personal tutor: a teacher's view. AB - The dramatic changes that have occurred in the National Health Service during the last decade have been mirrored in nurse education. Although these changes have had a positive impact, students and tutors may feel they have created additional stress. This article looks at the personal nurse tutor's role in helping students come to terms with events at a vulnerable time in their lives. Scientific and humanistic evidence for the role is presented, and a model is offered as guidance for good practice in personal tutoring. PMID- 8499285 TI - Learning disabilities: promoting 'ordinary life principles'. AB - People with learning disabilities who present challenging behaviours pose significant problems for staff who are keen to encourage in them a sense of community integration. This article relates the efforts of one group of staff in a community home who devised a programme that helped to transform the behaviours of four clients, enabling them to become actively involved in community activities. PMID- 8499286 TI - Rewarding nurses for their performance. PMID- 8499288 TI - Lateral nursing: back complaints to the hilt. PMID- 8499287 TI - School nursing: health promotion for school children. AB - This article discusses the findings of a retrospective study looking at the outcomes, in terms of health promotion of health interviews with children aged ten to 11, between 1989 and 1991. A total of 59 children cared for by three school nurses were available for follow-up. It was found that overall, the health promotion given to children was effective in nearly three quarters of the children seen. Problems with feet were the most commonly reported complaint. The author suggests that other districts should consider introducing health interviews into school nurses' work. PMID- 8499289 TI - Information technology: shareware. PMID- 8499290 TI - Cardiology update. Understanding atherosclerosis. PMID- 8499291 TI - Cardiology update. Using the Dundee Coronary Risk-Disk. PMID- 8499292 TI - Cardiology update. Garlic and the healthy heart. PMID- 8499293 TI - Cardiology update. A flawed policy. PMID- 8499295 TI - Unions support HIV guidance. PMID- 8499294 TI - Haemophilia nurses ask to be warned. PMID- 8499296 TI - Funding cut for HIV and AIDS. PMID- 8499297 TI - New treatment helpful in Kaposi's sarcoma. PMID- 8499298 TI - Homelessness: Portakabin care. PMID- 8499299 TI - A 'New Deal' for nurses too? PMID- 8499300 TI - Nurses work. Survey shows hidden cuts. PMID- 8499301 TI - Nurses work--the outcomes. PMID- 8499302 TI - Bereavement counselling. Coping with a child's death: a case study. AB - The death of a new-born baby causes unbearable pain for parents, family and careers. It is important that these feelings are released if a resolution of the experience of loss is to be achieved. The author presents a short case study showing how he helped one family come to terms with their grief. All names and circumstances have been changed to protect the identities of those involved. PMID- 8499303 TI - Volume reduction of arm lymphoedema. AB - Most of the volume reduction in an 11-day course of compression bandaging for severe cancer-related arm lymphoedema appeared to occur in the first few days. This study therefore compared the volume loss during days 1-4 with 5-11. Fifteen consecutive courses of bandaging were studied. Arm volume was estimated on days 1, 5 and 11. The volume reduction during days 1-4 was compared with days 5-11 using the Wilcoxan Ranked Pairs Test. Seventy nine per cent of the total median volume reduction occurred during days 1-4. The difference between the two periods was highly significant (p < 0.001). The duration of compression bandaging has therefore been reduced to 4 days for severe cancer-related arm lymphoedema in this clinic. PMID- 8499304 TI - Diagnosing hearing loss in children. AB - Hearing loss can have a dramatic effect on a child's development and language acquiring abilities, and can also pose significant strain on parents and siblings. It is therefore important that health visitors and nurses are aware of the signs of hearing loss in very young children, and understand what diagnostic and treatment options are available. The author describes what these options are. PMID- 8499305 TI - Working abroad: no longer an option? AB - Reductions in vacancies and career opportunities in the UK have led many nurses to consider working abroad. With many of the traditional choices such as Australia, the US, Canada and New Zealand also facing recessions, however, job opportunities are becoming increasingly limited, suggests James Buchan. PMID- 8499306 TI - Tomlinson: a social policy perspective (Part 1). AB - This article is the first of two which explore the Report of the Inquiry into London's Health Service, Medical Education And Research (1) (the Tomlinson Report), and consider its origins and implications from a social policy perspective. In this article, the Tomlinson Report will be placed within its historical context and the key events leading up to its commissioning and publication examined. To facilitate the analysis, a 'policy as process model' will be adopted throughout to articulate and emphasise the relationships between the phenomena involved (2). Part two appears next week. PMID- 8499307 TI - Witch hunting HIV in the workplace. PMID- 8499308 TI - The Standard guide to writing effective letters. PMID- 8499309 TI - Rude health. PMID- 8499310 TI - Informed consent: suffer the Children Act. PMID- 8499311 TI - Wound dressing: principles of choice. Pt 2 (continuing education credit). AB - The ability to select an appropriate wound dressing is an integral part of the nurse's role in assisting the wound healing process. The sheer range of dressings available can make that selection seem complex. This Learning Unit is the second of a series designed to help nurses choose appropriate dressings and so improve the care offered to patients and clients. PMID- 8499312 TI - Cigarette smoke causes rapid lipid peroxidation of rat tracheal epithelium. AB - Cigarette smoke-induced lipid peroxidation may be an important mechanism of smoke toxicity, but attempts to demonstrate peroxidation of pulmonary tissues after smoke exposure have yielded conflicting results. To examine this question, we exposed rat tracheal explants to whole smoke for 10 minutes followed by air recovery for periods up to 50 minutes (test), or to air alone (controls) and measured conjugated diene levels in the tissue. A dose-related increase in conjugated diene levels was seen in explants exposed to 1, 3 or 6 puffs of smoke. After exposure to 6 puffs of smoke, there was a progressive increase in conjugated diene levels during the first 10 minutes of air recovery; thereafter, test levels remained at about 1.5 times control. Pretreatment of the explants with superoxide dismutase, catalase, or deferoxamine prevented the increase in conjugated diene levels, and inactivation of the enzymes destroyed their protective effect. We conclude that cigarette smoke rapidly produces lipid peroxidation in tracheal segments in vitro, that the severity of the process is directly related to the amount of smoke exposure, and that inflammatory cells are not required for this effect. Lipid peroxidation in this system appears to be mediated by active oxygen species. PMID- 8499313 TI - Ultrastructural observations in copper-deficient guinea-pig lung cells. AB - Dietary copper deficiency is known to affect metabolism of neutral lipids, phospholipids, prostaglandins, Cu-Zn superoxide dismutase and crosslinks of connective tissues. To investigate the effects of copper deficiency on lung ultrastructure, dietary copper deficiency was induced by feeding female guinea pigs a diet marginally deficient in copper (0.8 microgram Cu/g diet) and compared with those fed a diet sufficient in copper (5.8 micrograms Cu/g diet). After 10 months on the diets, at age 340 days, animals were killed and the lungs removed and processed for electron microscopy to study the changes in cellular morphology. Type II epithelial cells in lung alveoli of copper deficient guinea pigs, revealed larger lamellar bodies, in comparison with lungs of copper supplemented guinea-pigs (2.1 +/- 0.67 vs 1.35 +/- 0.47 microns). Fusion of lamellar bodies had occurred. Lipid droplets were found in the cytoplasm, which, in 20% of these cells, was as a single large lipid droplet approximately 10 microns in diameter. Features of the bronchiolar Clara cells in response to copper deficiency included the formation of packed tubular structures, 50 nm diameter. These tubules resembled smooth endoplasmic reticulums, and occupied 35.6% of the cell profiles by stereologic analysis. Clara cells from copper deficient guinea-pigs also contained many uniform, hexagonal crystal structures, in greater concentration than reported previously. Residual macrophages and monocytes observed in the capillaries contained giant lipid inclusions, which were stained by Sudan Black, indicative of neutral lipids. In this study, we suggest that perturbations in protein, lipid and membrane metabolism resulting from dietary copper deficiency in the guinea-pig may have altered the synthesis or degradation of lipid and protein components of lung cells or prevented their normal secretion into the airways or extracellular spaces. PMID- 8499314 TI - The effects of hexane on rat myocardium: a morphometric and morphological study. AB - Specimens from the left ventricular myocardium of 10 rats that had been exposed to subcutaneously administered hexane for 30 days were morphometrically and morphologically examined. Other than the presence of occasional necrotic fibres in hexane-treated animals, there was little difference in the histological appearance of myofibres in control or experimental specimens. There was a slight reduction in the average diameter of cardiac myofibres after exposure to hexane. Pathological ultrastructural changes of the myofibres were noted in the experimental and not in the control groups. Mitochondrial oedema and necrosis and myofilament disorganization and dissolution were significant changes noted in the experimental group. These pathological changes suggest that hexane, a constituent of glue and benzine, is cardiotoxic. PMID- 8499315 TI - The ultrastructure of rat lung following acute primary blast injury. AB - While a number of workers have described the effects of blast waves upon the lung at both the macroscopic and light microscopic level, studies involving the use of the electron microscope have not been reported. In the experiments reported here the ultrastructural changes seen in lungs from rats exposed to a blast wave impacting on the right side of the chest are described. Considerable damage to the right lower lobe was observed which took the form of tearing of the inter alveolar septa with capillary rupture and intra-alveolar haemorrhage. Changes to the alveolar epithelium and type II pneumocytes were also noted. Lesions were also identified in the left lung; these included intra-alveolar oedema with a minimal amount of interstitial oedema together with increased pinocytosis and isolated rupture of the alveolar epithelium. 'Ballooning' of the endothelium into the lumen of the capillary was also observed. There was an indication that lesions noted in the left lung at the electron microscopic level may be progressive in the first 24 hours following injury. PMID- 8499316 TI - A comparative endpoint study of lesions induced by MoMuSV-m1, MoMuSV-HT1, MoMuSV 124 and MoMuSV-349. AB - Different MoMuSVs produced predictable clinical, gross, and histologic similarities and differences when inoculated into susceptible hosts intraperitoneally. The neoplasms induced by MoMuSV-124 and MoMuSV-349 were histologically indistinguishable. The distribution of the neoplasms was the most widespread in these two groups. Histologically, the neoplasms induced by MoMuSV 124 and MoMuSV-349 were best described as angioproliferative. The neoplasms induced by MoMuSV-HT1 were most accurately described as fibrosarcomas. Histologically, the neoplasms induced by MoMuSV-m1 had characteristics common to neoplasms induced by MoMuSV-124 and MoMuSV-349, but with a less prominent vascular component. All mice inoculated with these MoMuSVs had moderate to severe thymic atrophy. The degree of thymic atrophy associated with both MoMuSV-124 and MoMuSV-349 was histologically more severe than that associated with MoMuSV-m1 and MoMuSV-HT1. Both MoMuSV-HT1 and MoMuSV-m1 had infiltrates of primitive myeloid cells within the spleen. In the case of MoMuSV-m1, there was an apparent leukaemia with infiltrates of similar cells within the bone marrow. With MoMuSV HT1, these primitive cells were confined to the spleen. In summary, this study demonstrated that some of the different strains of MoMuSV (with the exception of MoMuSV-124 and MoMuSV-349), induced histologically distinct lesions in BALB/c mice. PMID- 8499317 TI - An assessment of myeloid colony-forming-cell generation in liquid human bone marrow cultures: influence of accessory cells and cytokines IL-1 alpha, beta and IL-6. AB - Liquid culture of Ficoll isolated human marrow mononuclear cells followed by secondary clonogenic assays has been used to study the involvement of specific accessory cells and cytokines on the kinetics in vitro of human granulocyte macrophage-colony forming cells (CFU-GM). Primary cultures produced an oscillation in CFU-GM numbers, typified by increases in CFU-GM after 4 and 9 days and reductions on days 2 and 4. Cultures of marrow cells depleted of mononuclear phagocytes produced a steady decline in CFU-GM number over a similar period. Removal of T cells was without effect. Comparison of colony assays using conditioned medium (CM) from the human bladder carcinoma cell line 5637 and 5637CM plus interleukin (IL)-3 revealed the decline of CFU-GM in mononuclear phagocyte depleted cultures due to lack of maturation of early myeloid progenitors. The cytokines IL-6 and IL-1 beta were detectable in the supernatant from whole marrow cultures and from cultures depleted of T cells but not in cultures depleted of mononuclear phagocytes. Using neutralizing polyclonal antibodies directed against IL-1 and IL-6, singly or in combination, in whole marrow cultures we showed that anti-IL-6 antibody alone had no effect on the number of colonies detected in the secondary clonogenic assay whilst anti-IL-1 and anti-IL-1 plus anti-IL-6 reduced colony counts by 44 and 83% respectively. Thus, endogenously produced IL-1 and IL-6 are involved in the dynamic changes in CFU-GM numbers when marrow mononuclear cells are cultured. Possible synergistic interactions are discussed. PMID- 8499318 TI - Intracranial metastases of induced lung carcinomas in rats. AB - Through 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA), metastasizing lung carcinomas were induced in 56 Hann: Wistar rats. Among them nine animals had intracranial metastases. Four metastases were localized in the pituitary, three in the choroid plexus of the IIIrd ventricle, one in the choroid plexus of the IVth ventricle, and one in the brain-stem. Thus, the preferential sites of intracranial metastasis were the choroid plexus of the ventricles and the pituitary. No metastatic spread was found in the cerebral hemisphere. Five of the metastatic tumours resembled the primary pulmonary adenocarcinoma. In the other four, the primary was an adenosquamous carcinoma but only adenocarcinomatous components were present in the metastasis. PMID- 8499319 TI - Binding of macrophages and B lymphocytes mediated by dengue virus antigen and the virus-induced helper cytokine. AB - Macrophage (M phi) process dengue type 2 virus (DV) antigen and present it to B cells leading to their clonal expansion and transmit DV-specific helper cytokine (HF) signal to B cells. The present study was, therefore, undertaken to investigate the binding of DV or HF-pulsed M phi with 51Cr- labelled B lymphocytes. The binding was dependent on the number of DV antigen positive M phi or dose of HF, period (peak with DV at 24 h and with HF at 4 h) and temperature of incubation. The binding was significantly increased by treating DV-pulsed M phi with DV-specific helper T cells or HF. Glutaraldehyde fixed M phi (which do not process DV antigen (Rizvi et al. 1989)) had poor binding capacity. The binding was DV- or HF-specific as it was inhibited by treatment of M phi with specific antisera. The findings thus show that M phi and B lymphocytes are actively bridged via DV antigen and HF to effectively transmit the antigen specific signal. PMID- 8499320 TI - Characterization of the murine model of schistosomal hepatic periportal fibrosis ('pipestem' fibrosis). AB - During mild (one to two pairs of worms) and prolonged (23 weeks or more) mouse infections with Schistosoma mansoni, but not with S. japonicum, periovular granulomas and fibrosis were seen to be preferentially located along periportal tissues. This caused fibrotic expansion of the portal spaces on a background of normal-looking hepatic parenchyma, a picture mimicking 'clay pipestem fibrosis' seen in human patients with advanced schistosomiasis. The model was reproduced in outbred and in several strains of inbred mice, and their main characteristics were studied and compared to the human counterpart. A balanced consideration of the similarities and differences between the murine model and human pipestem fibrosis is needed for the adequate utilization of this simple, reproducible and inexpensive experimental model. PMID- 8499321 TI - Effects of a hypercholesterolaemia-inducing diet on biliary electrolytes and lipid secretion in the rat. AB - The effects of a high cholesterol/cholate diet on the biliary secretion of bile acids, cholesterol, phospholipid and inorganic electrolytes in the rat were examined. Wistar rats were fed a hypercholesterolaemia-inducing diet (HID) for 20 days prior to the biliary experiments. Rats fed a standard laboratory diet were used as controls. The HID diet increased plasma cholesterol concentrations and the hepatic content of total, free and esterified cholesterol, without changes in ALP*, ALT and AST plasma activities. Bile flow and biliary secretion of bile acids and inorganic electrolytes were markedly increased in the hypercholesterolaemic animals. The stimulated biliary secretion was due to an increase in both the bile acid-dependent and bile acid-independent fractions of bile flow. An increase in the bile acid pool induced by the administration of exogenous cholic acid/cholesterol would account for these changes in bile flow and inorganic electrolyte secretion. Nevertheless, the increase in the bile acid independent bile flow could be also related, at least to some extent, to a higher efficiency of bicarbonate transport into bile. The HID diet also increased both cholesterol and phospholipid biliary outputs, whereas it did not modify the relationship between lipid and bile acid secretion. The lithogenic index of bile was reduced in the rats after the HID regimen due to a relatively higher increase in the biliary outputs of phospholipids and bile acids than of cholesterol. PMID- 8499322 TI - Hepatocyte membrane injury and bleb formation following low dose comfrey toxicity in rats. AB - Comfrey, a popular herbal remedy, contains hepatotoxic pyrrolizidine alkaloids and has been implicated in recent human toxicity. Although alkaloids from other plant sources have been extensively researched, studies on the hepatotoxic effects of comfrey alkaloids are scant. The effects of high dose comfrey toxicity have been studied and the present investigation was undertaken to identify changes associated with relatively low dose toxicity. Eight young adult rats were dosed weekly for six weeks with 50 mg/kg of comfrey derived alkaloids. The animals were dissected one week after the last dose and the livers examined by light and electron microscopy. Changes at the light microscopic level showed vascular congestion, mild zone 3 necrosis and loss of definition of hepatocyte cellular membranes. Extensive ultrastructural abnormalities were identified in the form of endothelial sloughing and the loss of hepatocyte microvilli. A striking finding was florid bleb formation on the sinusoidal borders of hepatocytes. Many blebs were shed into the space of Disse and extruded to fill, and sometimes occlude, sinusoidal lumina. Platelets were frequently found in areas of bleb formation. There was evidence of late damage in collagenization of Disse's space. Hepatocyte bleb formation is known to occur under a variety of pathological conditions but there is little to no information in the literature on the effects, if any, of bleb formation on fibrogenesis and the microcirculation and its role in the pathogenesis of liver disease. The pyrrolizidine alkaloids of comfrey may serve as an experimental tool to study the process of bleb formation and the intimate relationship between hepatocyte and sinusoidal injury in the liver. PMID- 8499323 TI - Response of pediatric low grade gliomas to chemotherapy. AB - Thirteen patients with low grade astrocytomas were treated with alkylating agent or platinum-based chemotherapy regimens. Eleven of these patients received chemotherapy as their initial postoperative treatment modality, and 2 others as treatment for progressive disease postradiation therapy. Responses were objectively determined using CT or MRI. One patient had a complete response (CR), 6 had partial responses (PR), and 3 others had stable disease (SD) as their best response. Clinical responses paralleled those determined objectively. Chemotherapy was well tolerated with the exception of ototoxicity in 4 patients treated with cisplatin. Despite good initial responses, 5 of 6 patients who received no further treatment postchemotherapy (4 PR, 1 SD) developed progressive disease 5-13 months after completing chemotherapy. The remaining 4 patients with objective responses or stable disease (1 CR, 2 PR, 1 SD), all received further postchemotherapy treatment with radiation therapy or surgery, and have not demonstrated disease progression. Our experience suggests that alkylator or platinum-based chemotherapy can successfully delay the growth of these locally infiltrative neoplasms, and should be considered in their primary management. Despite the experience of others, further therapy appears necessary in patients with residual CT or MRI abnormalities postchemotherapy. PMID- 8499324 TI - Germ cell tumors of the basal ganglia and thalamus. AB - The clinicopathological findings in 6 patients with germ cell tumors originating in the basal ganglia and thalamus are presented. Clinical, biological and diagnostic features were somewhat different from germ cell tumors in the pineal region. Early and comprehensive treatment is recommended because of the possible presence of nongerminomatous germ cell components. PMID- 8499325 TI - Endoscopic ventricular surgery. PMID- 8499326 TI - Risk factors in the outcome of children with minor head injury. AB - A subset of children with minor head injury is known to develop serious neurological consequences, but identifying this subset has been difficult. In adults, multiple variables such as skull fracture, Glasgow Coma Scale score, unconsciousness, and amnesia are significant factors that determine whether to admit the patient to the hospital and the patient's outcome. As an objective assessment of neurological function, however, the Glasgow Coma Scale has limited usefulness in children, particularly those under 36 months of age. We report our experience with 937 children having head injuries using a Glasgow Coma Scale modified for children (Children's Coma Scale). During the 6-year study period, 791 of the 937 children (84%) sustained minor head injuries (Glasgow Coma Scale or Children's Coma Scale score of 13, 14, or 15). The mean age of patients was 5.5 years. Males predominated over females by a 2:1 ratio. The most common cause of injury was a fall, followed by a pedestrian/motor vehicle accident. Seven hundred and thirty-nine of the 791 children were alert at the time of admission. Of these, 99 (13.4%) had lesions requiring surgery: 9 had subdural hematomas, 35 had epidural hematomas, 44 had depressed skull fractures, and 11 had other types of lesions. Two children (0.3%) with Glasgow Coma scores of 13 died after subsequent deterioration, 1 of a delayed epidural hematoma, the other of diffuse cerebral edema. Risk factors such as length of unconsciousness, presence of skull fractures, computed tomography findings, posttraumatic seizure, and Glasgow or Children's Coma scores were evaluated for their impact on the patient's outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499327 TI - Shunt obstruction: a preventable complication? AB - Mechanical shunt complications account for more than half of all shunt failures. This study compares the incidence and etiology of mechanical shunt failure in a recent series of 343 pediatric patients with a flow-regulating shunt, Cordis Orbis-Sigma valve (OSV; Cordis, Miami, Fla., USA) to a previous series of 1,719 pediatric patients with standard differential pressure (DP) valves. The 1- and 5 year shunt failure probabilities were 20.1 and 23.6%, respectively, for the OSV valve and 31.1 and 49%, respectively, for the standard DP valves. The incidence of slit ventricles was 8.2% for the OSV and 33.2% for the conventional DP valve. Proximal obstruction remained the commonest cause of failure in both groups. Valve obstruction was higher (18.3 vs. 9.7%) with the OSV, although the obstructions tended to occur mostly in the early postoperative period possibly for debris introduced at the time of insertion. This review of the mechanical complications reported in this and other series suggests that despite the complexity of the interactions between variables associated with the patient, the surgeon and the shunt, mechanical complications are to a significant degree preventable. Verification will require prospective randomized clinical trials. PMID- 8499328 TI - Cervicomedullary compression by separate atlantal lateral mass. AB - Compression of the cervicomedullary junction can result from a variety of congenital craniovertebral anomalies. We report an unusual case of cervicomedullary compression by a free lateral atlantal mass associated with contralateral occipito-atlantal fusion. PMID- 8499329 TI - Type II antagonists impair the DNA binding of steroid hormone receptors without affecting dimerization. AB - Two types of steroid antagonists exert their activity by different mechanisms when bound to the cognate receptor. Type I anti-progestins, such as RU486, induce DNA binding of the human progesterone receptor (hPR), while no hPR/DNA complexes were seen in gel shift assays in the presence of the type II anti-progestin ZK98,299 or RU50,331. ZK98,299-liganded hPR exerted significantly less tight nuclear binding than receptor complexes formed with RU486. Also a type II anti glucocorticoid (RU43,044) was detected which completely abrogated DNA binding of its cognate receptor in vivo. In keeping with the existence of two different classes of anti-progestins, agonist- or RU486-induced hyperphosphorylation of the two hPR isoforms present in the T47D breast cancer cells was not induced by ZK98,299. This lack of hyperphosphorylation was, however, not the cause but most likely the consequence, of the reduced ability of the hPR/ZK98,299 complex to interact with DNA. No "mixed-ligand" heterodimers were formed in vitro between hPR isoform A bound to ZK98,299 and R5020-liganded isoform B, but nuclear co translocation studies indicated that ZK98,299 efficiently induced hPR dimerization in vivo. PMID- 8499331 TI - Wild type and alternatively spliced estrogen receptor messenger RNA in human meningioma tissue and MCF7 breast cancer cells. AB - Human meningiomas are rich in progesterone receptors (PR), which appear to be expressed autonomously. To investigate whether estrogen receptor (ER) variants which do not bind the ligand, but may constitutively induce PR expression, prevail in meningioma, we amplified cDNA by PCR in order to detect mRNA coding for the ER in meningioma which were ER-negative/PR-positive at the protein level. We screened for a portion of the ER which includes the DNA binding domain, the hinge region and the ligand binding domain. For this part of the ER we found a wild type mRNA in all 8 meningiomas tested. No mutations were detected. Apart from this transcript we found two alternatively spliced products missing exons 4 and 7, respectively in 8/8 meningioma specimens. These two products were not exclusive for meningioma, since they were also detected in the MCF7 breast cancer cell line which was used as control. ER deletion mutants missing exon 7 have already been reported [Ref. 1; Molec. Endocr. 5 (1991) 1571-1577]. These are dominant negative. To our knowledge, this is the first report on ER mutants missing exon 4. The presence of ER variants missing exon 4, which is probably not able to bind heat shock protein 90 and therefore may be constitutively active, might explain the autonomous expression of PR in meningioma. PMID- 8499330 TI - Detection of aromatase and keratinocyte growth factor expression in breast tumors using reverse transcription-polymerase chain reaction. AB - It has been proposed that local production of estrogen may contribute to breast tumor growth, in part by regulating growth factor production. In view of this, we studied the expression of mRNAs for aromatase cytochrome P-450, the enzyme which catalyzes estrogen synthesis, and keratinocyte growth factor (KGF), a heparin binding growth factor specific for epithelial cells, in breast tumors. In order to detect mRNAs of low-abundance, reverse transcription-polymerase chain reaction (RT-PCR) was used. RNA from breast tumors and normal breast tissue was reverse transcribed and then amplified using oligonucleotide primers for human aromatase or KGF. Twelve of 15 breast tumor samples yielded variable amounts of aromatase PCR product, but consistently strong KGF PCR signals. Of the three aromatase mRNA negative samples, two gave weak KGF signals while one was negative for KGF. Both aromatase and KGF transcripts were also detected in all five normal breast tissue samples examined. These results indicate that a high proportion of breast tumors have the potential to produce aromatase and KGF, both of which could play important roles in their growth. The results also suggest that RT-PCR can be used to evaluate local expression of growth mediators in tumors. PMID- 8499332 TI - 5 alpha-Dihydro-11-deoxycorticosterone as a mineralocorticoid agonist and antagonist: evidence for a weak mineralocorticoid as an antagonist of potent mineralocorticoids. AB - To evaluate the possibility that 5 alpha-dihydro-11-deoxycorticosterone (5 alpha DH-DOC), a weak mineralocorticoid, is an antagonist of a more potent mineralocorticoid, aldosterone, 0.25 microgram aldosterone was injected into adrenalectomized rats simultaneously with 200-800 micrograms 5 alpha-DH-DOC and urinary Na/K ratio and Na and K excretion were evaluated. Urinary Na/K ratio and Na excretion were significantly lower than those of control rats regardless of whether rats were treated with 0.25 microgram aldosterone alone or 400-800 micrograms 5 alpha-DH-DOC alone. Urinary Na/K ratio and Na excretion of rats given a combination of 0.25 microgram aldosterone plus 400-800 micrograms 5 alpha DH-DOC were significantly higher than those of rats given 0.25 microgram aldosterone alone. None of the treatment caused significant changes in urinary K excretion. The results demonstrate that 5 alpha-DH-DOC, a weak mineralocorticoid, is an antagonist of the sodium-retaining action of a more potent mineralocorticoid, aldosterone. Progesterone which has weak mineralocorticoid activity is also known as an antagonist of more potent mineralocorticoids. The results of the present study demonstrate further evidence that weak mineralocorticoids may work as antagonists of more potent mineralocorticoids. PMID- 8499333 TI - Protein-protein interactions between the DNA-binding domains of nuclear receptors: influence on DNA-binding. AB - The glucocorticoid and thyroid hormone receptors have the capacity to bind as dimers to palindromic DNA-binding sites. Protein-protein interactions between the DNA-binding domains of glucocorticoid receptor dimers restrict the DNA-binding to elements where the half-sites are separated by three base pairs, whereas DNA binding by the thyroid hormone receptor does not appear to require a strict half site spacing. We have previously shown that a five amino-acid segment close the the C-terminal zinc-binding site (D-box) was involved in dimerization of the glucocorticoid receptor (GR) DNA-binding domain (Dahlman-Wright et al., 1991, J. Biol. Chem., 266, 3107-3112). Here we provide functional evidence, using mutated thyroid hormone receptor DNA-binding domains, that this five amino acid segment (D-box) of the GR interacts with the equivalent segment on the second DNA-binding domain in the dimer. In contrast, the thyroid hormone receptor DNA-binding domain binds to palindromic thyroid hormone response elements in a weakly co-operative manner, independent of the D-box. PMID- 8499334 TI - Endocrine differentiation of the XY sex-reversed mouse ovary during postnatal development. AB - When the mouse Y chromosome of Mus musculus domesticus is placed onto the C57BL/6J genetic background, half of the XY progeny develop bilateral ovaries and the female phenotype, but lack regular estrous cyclicity and lose embryos after fertilization. In the present study, we compared the endocrinological activity of XY ovaries with XX ovaries during postnatal development by measuring steroids in the incubation medium by radioimmunoassay. At 1 day postpartum (d.p.p.), production of progesterone and estradiol was significant while testosterone was undetectable in both ovaries. At 14 and 35 d.p.p., amounts of testosterone and estradiol produced by XY ovaries were half of those by XX ovaries. Production of progesterone by XY ovaries was slightly higher than XX ovaries at 14 d.p.p., but only half of that at 35 d.p.p. Addition of gonadotropins increased testosterone production by XX ovaries but not by XY ovaries at either 14 or 35 d.p.p. Progesterone production in XY ovaries at 35 d.p.p. was increased by gonadotropins to a much lesser extent than in XX ovaries. Gonadotropins increased estradiol production similarly in both ovaries at 35 d.p.p. Striking differences were found in the histochemical distribution of 3 beta-hydroxysteroid dehydrogenase between XY and XX ovaries at 14, but not at 35 d.p.p. In conclusion, the XY ovary develops abnormal endocrine features during the postnatal period, which likely lead to the fertility problems at puberty. PMID- 8499335 TI - Identification of progesterone binding sites in the plasma membrane of the filamentous fungus Cochliobolus lunatus. AB - Plasma membrane associated binding sites for progesterone have been identified in the filamentous fungus Cochliobolus lunatus (C. lunatus). The Kd for progesterone determined by Scatchard analysis was 13.9 +/- 5.7 nM and the Bmax was 250-360 fmol/mg protein. A broad ligand specificity of these binding sites is suggested by the observation that all tested steroids, regardless of their capability to act as inducers of the 11 beta-steroid hydroxylase, competed at 250-fold excess with [3H]progesterone binding. A biological role of these plasma membrane associated steroid binding sites is nevertheless suggested since in protoplasts which were devoid of them, 11 beta-steroid hydroxylase could not be induced. Progesterone binding sites were present in the plasma membrane as well as in the cytosol and were detected in this fraction, in contrast to the plasma membrane fraction, only under special experimental conditions in respect to redox state. Kd and Bmax of cytosol binding sites were of the same order of magnitude compared to the plasma membrane progesterone binding sites. Ethisterone and 4-cholesten-3 one which cannot induce 11 beta-hydroxylase competed efficiently for plasma membrane binding sites; ethisterone, however also competed for cytosol binding sites and acted, in contrast with 4-cholesten-3-one, as antagonist in the induction of 11 beta-steroid hydroxylase in C. lunatus. On the basis of presented evidence we concluded that C. lunatus contains binding sites for steroids in the plasma membrane and in the cytosol and that both types of binding site are involved in the process of induction of enzymes which transform steroids in this fungus. PMID- 8499336 TI - Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha tetrahydroprogesterone. AB - The effects of sodium phenobarbital and sodium barbital on the activity of the particulate and cytosolic 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductases (3 alpha-HSORs) of female rat anterior pituitary were investigated. By altering the 3 alpha-HSOR catalyzed conversion of 5 alpha dihydroprogesterone (5 alpha-DHP) to 3 alpha,5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP), these barbiturates could influence the in situ production of 3 alpha,5 alpha-THP. 3 alpha,5 alpha-THP has potent barbiturate-like effects on brain GABAA receptors. Both phenobarbital and 3 alpha,5 alpha-THP can affect gonadotropin release in female rats. In vitro incubations of each 3 alpha-HSOR activity were assayed in the presence of sodium phenobarbital (0.1 to 10.0 mM) or sodium barbital (1.0 to 10.0 mM). Since both 3 alpha-HSOR activities catalyze the reversible oxidoreduction of 5 alpha-DHP and 3 alpha,5 alpha-THP, we examined the effect of these barbiturates not only on the conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP (reductive reaction) but also on the "back conversion" of 3 alpha,5 alpha-THP to 5 alpha-DHP (oxidative reaction). The results indicate that both phenobarbital and, to a lesser extent barbital, significantly affected the activities of the two 3 alpha-HSORs in both reductive and oxidative directions. In the reductive direction, phenobarbital inhibited the activity (33%) of both cytosolic and particulate enzymes which would presumably decrease the levels of 3 alpha,5 alpha-THP. In the oxidative direction, a pattern of stimulation was observed (20 to 100%). Thus, this stimulatory effect on the oxidative conversion of 3 alpha,5 alpha-THP to 5 alpha-DHP, which would presumably also decrease 3 alpha,5 alpha-THP levels, appears correlated with the inhibitory effect of these barbiturates on the reductive conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP. Sodium barbital exhibited somewhat similar effects. These changes suggest that barbiturates can lower 3 alpha,5 alpha-THP levels in the anterior pituitary. The results also suggest the possibility that lowered 3 alpha,5 alpha-THP levels may be involved, at least in part, in the reduction of gonadotropin release by barbiturates. PMID- 8499337 TI - Progesterone and dexamethasone inhibition of estrogen-induced synthesis of DNA and complement in rat uterine epithelium: effects of antiprogesterone compounds. AB - Progesterone (P) blocks estrogen induction of cell proliferation and synthesis of complement C3 in the epithelium of the immature rat uterus. Here it is shown that dexamethasone (Dex) exerts a similar inhibitory effect on these two parameters. Furthermore, analysis of the newly synthesized, secreted proteins produced during a 20 h explant culture period showed that not only does the uterus synthesize complement C3 but it is capable of proteolytically cleaving complement into its biologically active peptides. Since large doses of P are required for its inhibitory effects and since P can interact with the glucocorticoid receptor (GR), the role of the GR in mediating the P effect was questioned. Two antiprogesterone compounds with reportedly differing antiglucocorticoid activity, ZK98.734 and RU486, were tested for their ability to antagonize the inhibitory actions of P and Dex. Attenuation of estrogen-induced epithelial DNA synthesis by either P or Dex was fully overcome by concurrent administration of either ZK98.734 or RU486. On the other hand, while either antagonist was effective against the inhibitory action of P on estrogen-induced complement C3 synthesis, only ZK98.734 was fully effective in blocking inhibition by Dex. Thus, unlike its activity in rat hepatic cells, ZK98.734 is a potent antiglucocorticoid in the immature rat uterus. Because of this antiglucocorticoid activity, differential antagonism of the P response was not possible using these two steroid analogs. Although these observations support the notion of GR mediated inhibition of estrogen action in the uterus, they do not answer the question of whether P might act through a GR mediated pathway. PMID- 8499338 TI - Antiandrogenic property of RU 486: enhancement of estrogen-induced uterine peroxidase activity in the rat. AB - The contragestational steroid RU 486 enhanced the increase in peroxidase activity produced by estradiol in estrogen-primed immature rat uteri and, like the antiandrogen flutamide, RU 486 reversed the inhibitory effect of testosterone on this estrogen-induced response. It antagonized the inhibition produced by progesterone but had no effect on peroxidase induction by itself or in unprimed immature animals. RU 486 also enhanced the effect of estradiol on the synthesis of complement component C3 in the rat uterus. The results confirm that RU 486 possesses antiandrogenic as well as antiprogestational properties. They also suggest that, in normal adult animals, the increase in peroxidase activity in the uterus in response to estrogen is not expressed fully but held in check by other endogenous steroids acting through their individual receptors. PMID- 8499339 TI - Effect of onapristone and medroxyprogesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells. AB - We studied the influence of the antiprogestin onapristone (ZK 98.299) and the progestin medroxyprogesterone acetate (MPA) on the proliferation and hormone receptor levels of the following human breast cancer cell lines: the oestrogen receptor (ER) and progesterone receptor (PR) negative cell line MDA-MB-231 and the ER- and PR-positive cell lines T47-D and SK-BR-3. MPA and onapristone both bind to the cellular PR and can inhibit the proliferation of hormone-dependent cells; PR-negative MDA-MB-231 cells are not inhibited. The growth inhibition of the ER- and PR-positive tumour cells induced by onapristone is accompanied by a significant accumulation of cells in the G0/G1 phase and a reduction of S-phase cells, while MPA does not change the distribution of the cell cycle phases. However, MPA reduces the cellular ER content by 27% and the PR content by more than 80%. Conversely, onapristone does not significantly affect ER and PR levels. The extent of growth inhibition by both drugs differs considerably: onapristone inhibits growth of both receptor positive cell lines (T47-D:39%; SK-BR-3:17%), while MPA affected growth in only SK-BR-3 (61%). These results indicate that even though the two drugs act through the PR, the inhibitory effect on the three cell lines of MPA may depend on ER concentration and its down-regulation, while the inhibitory effect of onapristone is mainly correlated to the PR concentration without significantly affecting ER levels. Since tumour cells with low ER concentration are growth suppressed by onapristone, but not by MPA, it remains to be examined whether antiprogestins should preferably be used in PR-positive tumours with a low ER concentration. PMID- 8499340 TI - The effect of epitestosterone on the plasma levels of LH and FSH in ovariectomized immature rats. AB - Immature ovariectomized female rats primed with estradiol or without estrogen priming were treated with epitestosterone i.p. After 7 h blood was collected and LH and FSH levels were determined. The dose-response relationship was a biphasic one. LH and less markedly FSH levels decreased under epitestosterone treatment with doses up to 10 mg, whereas at higher doses an increase of gonadotrophins was observed. PMID- 8499341 TI - The free androgen index is not valid for adult males. AB - The Free Androgen Index (FAI) was initially proposed as a measure for assessing the circulating testosterone availability in female hirsutism. The extension of its use, by a number of investigators, to males has not been formally justified. An analysis of its derivation from the Law of Mass Action reveals an implied assumption that the binding capacity of sex hormone binding globulin should greatly exceed the concentration of its ligand testosterone. This does not hold in adult males for whom the use of FAI is therefore inappropriate. A comparison of FAI and free-testosterone (determined by centrifugal ultrafiltration) yielded a correlation coefficient (r) of 0.858 for 20 adult females but only 0.435 for 19 adult males. PMID- 8499342 TI - Testosterone induces expression of transforming growth factor-beta 1 in the murine thymus. AB - Castration of adult male mice results in enlargement of the thymus and diminution of peripheral suppressor T cell function. Replacement therapy with physiologic doses of androgens reverses these phenomena. Although the mediators involved are unknown, these effects of androgens on the thymus and peripheral immune system are reminiscent of those reported for transforming growth factor-beta (TGF-beta 1). We examined expression of TGF-beta 1 mRNA and bioactive protein in thymuses from castrate and androgen-replaced animals. Steady-state levels of thymic TGF beta 1 mRNA fell slightly after castration, but rose 2.3-fold after testosterone replacement. Bioactive TGF-beta 1 production by cultured thymic explants also fell following castration to approx. 50% of the levels observed in intact animals. Following 1 week of testosterone replacement in castrate animals, TGF beta 1 bioactivity produced in culture was restored to levels indistinguishable from those observed with explants from intact animals. Reverse transcription/polymerase chain reaction amplification of RNA revealed that thymocytes are a source of the androgen-modulated TGF-beta 1. These results suggest that TGF-beta 1 may mediate effects of androgens on the immune system. PMID- 8499343 TI - Testosterone down-regulates the levels of androgen receptor mRNA in smooth muscle cells from the rat corpora cavernosa via aromatization to estrogens. AB - Androgens down-regulate the levels of androgen receptors (AR) and AR mRNA in the penis and prostate of castrated rats, and are assumed to cause their decrease during sexual maturation in the penile smooth muscle of intact rats. In order to determine whether these effects occur directly at the target cell level, and to what extent they are due to testosterone (T) or to their metabolites, we have measured AR mRNA in cultures of smooth muscle cells from the adult rat corpora cavernosa treated in vitro with sex steroids. T at high concentrations (100 nM) acted like dihydrotestosterone (DHT) in increasing moderately the levels of AR mRNA in both proliferating and contact-inhibited cells. However, when conversion of T to DHT was blocked by the 5-alpha reductase inhibitor finasteride, the levels of AR mRNA were considerably down-regulated by T (10-500 nM), particularly in the contact-inhibited cells. Finasteride by itself was inactive. These effects in both types of cultures were inhibited by platelet derived growth factor (PDGF) (20 ng/ml), a growth factor that up-regulates AR mRNA levels, and by fadrozole (100 nM), an aromatase inhibitor of the T/estrogen conversion. Estradiol (50 nM) was even more potent than T in decreasing AR mRNA levels. With the exception of PDGF none of the treatments affected significantly cell growth, as measured by DNA synthesis and content. Our results indicate that it is possible to modulate in vitro AR mRNA levels in the penile smooth muscle cells, and that under normal conditions DHT and T act as moderate up-regulators. When DHT formation is inhibited, the aromatization pathway of T to estradiol will prevail and induce a pronounced down-regulation of AR mRNA levels. We assume that the in vivo AR down regulation in the penile smooth muscle by androgens is an indirect effect mediated by a paracrine or endocrine mechanism elicited in another tissue. PMID- 8499344 TI - Human endometrial 3 beta-hydroxysteroid dehydrogenase/isomerase can locally reduce intrinsic estrogenic/progestagenic activity ratios of a steroidal drug (Org OD 14). AB - In vitro conversion in human endometrial tissue of Org OD 14 [17 alpha-hydroxy-7 alpha-methyl-19-norpregn-5(10)-en-20-yn-3-one, a 3-keto-delta 5-10-19 nortestosterone derivative structurally related to norethynodrel] to its 4-ene isomer was demonstrated and measured spectrophotometrically and by chromatographic separation of the labeled metabolite from the tritiated precursor. The endometrial isomerase catalyzing this conversion is the 3 beta hydroxy-steroid dehydrogenase/isomerase (3 beta HSD/isomerase), detected by Western blotting as a 42 kDa band, as confirmed by the inhibition of Org OD 14 isomerization with an antibody against this enzyme. The endometrial isomerase activity was found to be higher in secretory than in proliferative tissue and to be influenced by progestins, as suggested by the small but significant increase in activity resulting from exposure of proliferative endometrium to medroxyprogesterone acetate under organotypic culture conditions. In addition to the expected physiologic importance of endometrial 3 beta HSD/isomerase in the local metabolism of circulating steroids of adrenal origin, its presence in the endometrium is likely to have pharmacologic relevance, as illustrated by the local conversion of Org OD 14 to the 4-ene isomer, a metabolite with higher progestagenic and lower estrogenic potencies than those of its precursor. The local, tissue-specific, modification of the precursor would yield intracellular concentration ratios of Org OD 14 to 4-ene isomer in the endometrium significantly lower than those in blood. As a result, the estrogenic effects of Org OD 14 or of its 3-hydroxy metabolites on endometrial cell proliferation are minimized by the local formation of the progestagenic 4-ene isomer. This is a favorable feature of Org OD 14 since it selectively prevents undesirable proliferative stimulation of the endometrium in postmenopausal users while preserving its beneficial effects on other tissues, including bone. PMID- 8499345 TI - Further characterization of the testosterone inducible protein fraction from the mouse fetal male reproductive tract inducing masculine differentiation in vitro. AB - Recently, we identified a protein fraction with phospholipase A2 (PLA2) stimulatory activity (named as PLSP in previous publications) from the fetal male reproductive tract which induced masculine differentiation of the Wolffian duct in vitro. The role of the PLA2-stimulatory activity of this protein was not clear from the past investigations and the present study was designed to elucidate its role. PLSP as expected stimulated snake venom PLA2 and it induced masculinization not only in male explant but also in female explants in a dose-dependent manner in the absence of gonads. However, neither its PLA2-stimulatory activity nor its masculinizing activity was affected after passing it through a PLA2-Sepharose column (a compound expected to eliminate any PLA2 binding component) suggesting that the PLA2-stimulatory activity of PLSP was not at the level of PLA2 enzyme. To investigate whether modulation of the PLA2 substrate by PLSP played a role in producing PLA2-stimulatory activity, we determined the effect of increasing amounts of unlabeled substrate on the PLA2-stimulatory activity induced by PLSP. However, no change in the PLA2-stimulatory activity of PLSP by unlabeled substrate was noticed suggesting against this possibility. The PLA2-stimulatory activity of PLSP, however, was found completely abolished when it was subjected to extensive dialysis, while its protein composition and masculinizing activity remained unaffected. Thus, it appears that PLA2-stimulatory activity of PLSP is associated with a small compound co-purified with masculinizing protein of PLSP and this activity plays no role in inducing masculinization by PLSP. PMID- 8499346 TI - Characterization of 11 beta-hydroxysteroid dehydrogenase of human placenta: evidence for the existence of two species of 11 beta-hydroxysteroid dehydrogenase. AB - The enzyme, 11 beta-hydroxysteroid dehydrogenase converts the active glucocorticoids cortisol and corticosterone to their inactive 11-oxo metabolites cortisone and dehydrocorticosterone, respectively. The properties of the human placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) were studied. The enzyme was active in the oxidative and reductive directions. pH optimum for 11 beta-dehydrogenase activity was in the range of 7-10 and for 11-oxoreductase it was in the range of 5.5-6.0. The crude placental homogenate was unstable. Reductase activity was more labile than dehydrogenase activity. Removal of cytosol enabled the enzyme to retain activity. 11 beta-HSD a membrane bound enzyme was distributed in all particulate subcellular fractions. Addition of detergent released latent activity of 11 beta-dehydrogenase and inactivated 11 reductase activity. Both corticosterone and cortisol were substrates for the enzyme. The Km value with corticosterone as substrate was much lower than with cortisol. The Km values with cortisone and dehydrocorticosterone were similar. PMID- 8499347 TI - In vitro bioassays of non-steroidal phytoestrogens. AB - Some of the isoflavonoids present in human diet as well as in urine are expected to exert biologic effects as they have been reported to bind to estrogen receptors and to be estrogenic in other species. This report describes the in vitro assessment of estrogenic effects of isoflavonoids using human endometrial cells and tissue. The relative estrogenic potencies (EC50 values) of estradiol, 3 dietary isoflavonoids (coumestrol, genistein and daidzein) and one of their metabolites (equol), were estimated by using a recently developed multiwell plate in vitro bioassay based on the estrogen-specific enhancement of alkaline phosphatase (AlkP) activity in human endometrial adenocarcinoma cells of the Ishikawa-Var I line. The maximal AlkP activity elicited by the isoflavonoids tested was as high as that achieved with estradiol and their effects were suppressed by the antiestrogens 4-hydroxytamoxifen and ICI 164,384. These results indicate that estradiol and the isoflavonoids exert their effects on AlkP by similar interactions with the estrogen receptor, with potencies depending on binding affinities. The estrogenic effect of equol was confirmed by another in vitro bioassay, based on the estrogen-stimulated enhancement of prostaglandin F2 alpha output by fragments of human secretory endometrium. PMID- 8499348 TI - Metabolism of the oral contraceptive steroids ethynylestradiol, norgestimate and 3-ketodesogestrel by a human endometrial cancer cell line (HEC-1A) and endometrial tissue in vitro. AB - Human endometrial cancer cells and human endometrial tissue have been extensively used to study steroid hormone action and metabolism. The natural estrogens estradial (E2) and estrone (E1) are known to be metabolized by both cells and tissue with the interconversion of the two steroids and the formation of sulphate conjugates. The aim of the present work was to see if the commonly used oral contraceptive steroids ethynylestradiol (EE2), norgestimate (Ngmate) and 3 ketodesogestrel (3-KDG) were metabolized by a human endometrial cancer cell line (HEC-1A) and human endometrial tissue in vitro. Metabolites were analysed by on line radiometric HPLC. Endometrial tissue was obtained from women undergoing dilation and curettage or hysterectomy operations. In preliminary studies with endogenous estrogens, HEC-1A cells were able to interconvert E1 and E2; the equilibrium favouring the formation of E2. Normal endometrial tissue extensively converted E2 to E1, tumour tissue appeared to catalyse this reaction much less avidly. In addition sulphate conjugates were formed by normal tissue from some patients. Cell line and endometrial tissue was able to hydrolyse estrone 3 sulphate. With EE2 as substrate there was no evidence of phase I metabolism by cell line or tissue. However, conversion to the presumed 3-sulphate conjugate was observed following incubation with normal tissue from some women. Deacetylation of the progestogen Ngmate to norgestrel oxime (NgOx) was complete within 24 h. There was also some loss of the oxime moiety to give norgestrel (Ng) following incubation with HEC-1A cells. Metabolism of Ngmate was also complete within 24 h following incubation with endometrial tissue. There were both qualitative and quantitative differences in metabolite formation between tissue obtained from different women. In contrast, 3-KDG was relatively resistant to metabolism by cell line and tissue. The major metabolite formed by HEC-1A cells accounted for only 3.3 +/- 0.4% of total added radiolabelled steroid and co-chromatographed with 3 alpha-hydroxydesogestrel. Smaller amounts of other radiometabolites were formed. No phase I metabolites of 3-KDG were formed by normal endometrial tissue, however small amounts of radiometabolites appeared to be formed by malignant tissue. These studies have provided evidence to suggest that the oral contraceptives EE2, Ngmate and 3-KDG are metabolized in the human endometrium. Knowledge of the metabolism of these in target tissues such as the endometrium may be pertinent considering the possibility that metabolites may exert specific effects. PMID- 8499349 TI - New identified 15 beta-hydroxylated 21-deoxy-pregnanes in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AB - The identification of 3 new 15 beta-hydroxylated 21-deoxy-pregnanes in the urinary steroid profile of a 4-month-old girl with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is reported here. These steroids were identified by gas chromatography and gas chromatography-mass spectrometry as 3 alpha,15 beta,17-trihydroxy-5 alpha-pregnan-20-one (5 alpha II), 3 alpha,15 beta,17,20 alpha-tetrahydroxy-5 alpha-pregnane, and 3 alpha,15 beta,17,20 alpha tetrahydroxy-5 beta-pregnane (20 alpha DH-II). Two other compounds in the urine, 3 beta,15 beta,17- trihydroxy-5 alpha-pregnan-20-one and 3 beta,15 beta,17 trihydroxy-5 beta-pregnan-20-one were also characterized. The identification of the former 3 steroids was obtained by comparing their methylene unit values and mass spectral data with the corresponding data of the standard steroids synthesized from 15 beta,17-dihydroxy-4-pregnene-3,20-dione. Seven other synthesized and identified 15 beta-hydroxylated steroids were 3 alpha,15 beta,17 trihydroxy-5 beta-pregnan- 20-one (II), 3 alpha,15 beta,17,20 beta-tetrahydroxy-5 beta-pregnane, 15 beta,17-dihydroxy-5 alpha-pregnane-3,20-dione, 15 beta,17 dihydroxy-5 beta-pregnane-3,20-dione, 3 alpha,15 beta-dihydroxy-5 alpha-androstan 17-one (15 beta OH-An), 3 alpha,15 beta-dihydroxy-5 beta-androstan-17-one (15 beta OH-Et) and 3 alpha,15 beta,17,20 beta- tetrahydroxy-5 alpha-pregnane. Of these the latter two have not been reported previously. This study supports the findings that 15 beta-hydroxylated steroids are common in the neonate and could play an important role in the diagnosis of CAH due to 21OHD, where II and the newly identified steroids from this investigation viz., 5 alpha II and 20 alpha DH-II appear the most important 15 beta-hydroxysteroid markers for this disease. PMID- 8499350 TI - Cortisol metabolism in vitro--II. Species difference. AB - It has been suggested that cortisol 6 beta-hydroxylase activity specifically reflects cytochrome P4503A (CYP3A) levels in the liver. However, we have previously reported that the metabolism of cortisol in human liver fractions in vitro is extremely complex and variable, and therefore complete metabolite analysis must be undertaken if 6 beta-hydroxycortisol is to be used as a marker of CYP3A activity. In the present study, the metabolism of [3H]cortisol by hepatic microsomes from various animal species, and by cytosol from male and female rats, has been defined and compared with metabolites formed by human liver microsomes. Metabolites were characterized by co-chromatography with authentic standards, mass spectrometry, and quantified by radiometric HPLC. The results show that all microsomes prepared from animal species studied (male and female rat, male and female guinea-pig, male hamsters and mice) can metabolize cortisol, although the metabolic profiles are both quantitatively and qualitatively different from that obtained with human microsomes. In general the metabolic profiles for animal microsomes are simpler: hamster, mouse and guinea pig show only 6 beta-hydroxylase and 11 beta-dehydrogenase activity, although male rat shows both of these and 20 beta-reductase activity while the female rat possesses all of the above as well as the ability to reduce the A-ring (delta 4-reductase and 3-oxidoreductase activities). The female rat also produces two metabolites undetected in humans. Incubations with male rat cytosol generated 20 beta dihydrocortisone as the major metabolite, and several unidentified minor polar metabolites, whereas female cytosolic products were identical to those generated by human cytosol, the major metabolite being 3 alpha,5 beta-tetrahydrocortisol. In conclusion, our studies have shown that hepatic cortisol metabolism is extremely variable amongst the species investigated and that the hamster provides the simplest model with which to explore cortisol 6 beta-hydroxylase activity. PMID- 8499351 TI - Role of endogenous opioids in progesterone antagonism on oestradiol-induced DNA synthesis in the rat uterus. AB - To probe the possible involvement of endogenous opioid peptides (EOPs) in progesterone (PG) antagonism on oestradiol-17 beta-(OE) induced uterine cell proliferation, the opioid antagonist naltrexone hydrochloride (NTX) and anti [Met5]-enkephalin antiserum (AME) were investigated for their effect on uterine DNA synthesis in ovariectomized rats pretreated with OE and PG 24 h before killing. As an index of DNA synthesis the rate of in vitro incorporation of [3H]thymidine ([3H]TdR) into DNA was measured. The inhibitory effect of PG on OE induced DNA synthesis could be diminished by approximately 42 and approximately 20% by the NTX treatments given directly into the uterine horns 13 and 4h before killing, respectively. Intraluminal AME treatments were only effective when they were administered 13 h before decapitation. Systemic blockade of opioid receptors by intraperitoneal NTX injections given every 6 h to the OE + PG-treated rats did not result in the disinhibition of uterine [3H]TdR incorporation. Our results suggest the involvement of EOPs--including [Met5]-enkephalin--as autocrine/paracrine factors in the PG antagonism on OE-induced uterine DNA synthesis. PMID- 8499352 TI - Laser corneal surgery. Proceedings of the 2nd annual congress of the Summit International Laser User Group. Montreux, Switzerland, September 46, 1992. PMID- 8499353 TI - Excimer laser photorefractive keratectomy for myopia: clinical results in 96 eyes. PMID- 8499354 TI - Photorefractive keratectomy for myopia: 6-month results in 95 eyes. AB - Ninety-five eyes of 91 patients with myopia from -1.00 to -6.00 D (mean -3.40 D, +/- 1.2) were treated with an ExciMed UV2OOLA 193-nanometer excimer laser (Summit Technology, Inc, Waltham, Mass) (with version 5.5 software) with a 5-millimeter ablation zone. At 6 months, 67 eyes (70%) were within +/- 0.50 D, 84 eyes (88%) were within +/- 1.00 D, and 94 eyes (99%) were within +/- 2.00 D. There was an average overcorrection of +0.25 D which had decreased to +0.18 D by 9 months. Best spectacle corrected visual acuity was 6/6 or better in 88 eyes (94%) and six eyes (6%) had a corrected visual acuity of 6/9. Fifty percent of eyes had slight astigmatism (mean 0.68 D, range 0.25 to 2.00 D) and this reduced to 0.33D (0.02 > p > 0.01) at 6 months. PMID- 8499355 TI - Double-blind corticosteroid trial in identical twins following photorefractive keratectomy. AB - The use of topical corticosteroids following excimer laser photorefractive keratectomy (PRK) is widespread, but the role of corticosteroids remains poorly defined. The purpose of this study was to evaluate the use of different corticosteroid postoperative regimens following 193-nanometer excimer PRK in identical twins. Preoperatively, cycloplegic refraction of the left eye of each twin measured -3.00 D sphere. The full correction was treated utilizing the identical technique within the same 30 minute period. The study was conducted in a double-blind fashion and the refraction, corneal clarity, uncorrected and best spectacle corrected visual acuity, and keratometry were assessed over the 6-month study period. Both twins were placed on an identical regimen, tapering their drops over a 3-month period. Corneal clarity was remarkably well preserved with essentially clear corneas observed in both twins. Similarly, both twins achieved 20/15 vision with a cycloplegic refraction of +0.75 D at 6 months. The only difference in the healing pattern was the slightly more rapid visual recovery in twin A. The code was revealed upon the cessation of corticosteroid regimen. Twin A had received fluoromethalone 0.1% and Twin B received dexamethasone 0.1%. Keratometry demonstrated identical flattening. There were no corticosteroid induced intraocular pressure rise or other complications noted. Identical twins presented a unique opportunity to better understand wound healing following laser keratectomy. The results of this limited study indicated that for at least lower degrees of myopia the need for full strength topical corticosteroids remains questionable. PMID- 8499356 TI - Photorefractive keratectomy for myopia: 18-month results in 178 eyes. AB - To evaluate the predictability, efficacy, and stability of myopic photorefractive keratectomy (PRK), we present the results of 18 months of 178 consecutive myopic eyes. Results demonstrated a stable change in the power of the cornea with long term corneal clarity. PMID- 8499357 TI - Photorefractive keratectomy in 202 myopic eyes: one year results. AB - We performed one-step procedures of photorefractive keratectomy (PRK) with the use of the excimer laser (193 nm) on 1519 myopic eyes during 1 year. From this group, we prospectively evaluated visual and refractive results of 202 (13%) consecutive myopic eyes that were followed for more than 1 year. Myopic eyes were divided into two groups according to the amount of myopia: group I, 135 eyes, 87 patients, less than -7.00 D, and group II, 67 eyes, 48 patients (-7.25 D to 13.50 D). The excimer laser system used was the ExciMed 200UV (Summit Technology, Inc, Waltham, Mass), the one-step computer program was fixed at a maximum ablation up to -6.00 D correction. Uncorrected visual acuity of 20/25 or better was achieved in 89.6% of eyes in group I and 47.8% in group II at 1 year. Best spectacle corrected visual acuity was equal to, or better than, the preoperative level in 93.8% of eyes. The difference between attempted and achieved refractive correction was within +/- 1.00 D in 91.4% in group I, and 51.7% in group II. The mean reduction of manifest (spherical equivalent) refraction in group II was 6.84 D at 1 year. Keratometric readings and central corneal thickness showed gradual changes until 6 months after surgery. Corneal haze disappeared in most of eyes at 1 year. The most common subjective complaint was glare and/or decreased vision at night or under dim light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499358 TI - Plume emission, shock wave and surface wave formation during excimer laser ablation of the cornea. AB - Excimer lasers are now used for corneal surgery; however, the physical processes occurring during photoablation of the cornea are incompletely understood. High speed laser-based photographic arrangement was constructed. The temporal resolution was better than 1 ns. The setup could work as a Schlieren arrangement, which is sensitive to the refractive index change caused by the shock wave propagating in the air above the eye. With minor changes the setup was converted into a shadowgraph, which could detect the ablation plume and the waves propagating on the surface of the eye. Due to the impact of the excimer laser pulse onto the surface of the cornea, a shock wave was generated in the air. The shadowgraph clearly showed the ejection of the ablated cornea. The ejection velocity of the plume was found to be over 600 m/s. It was shown for the first time that the recoil forces of the plume are generating a wave on the surface of the eye. The laser-based high speed photographic arrangement is a powerful arrangement in the study of physical effects occurring during photoablation of the cornea. PMID- 8499359 TI - Phototherapeutic keratectomy in nine eyes with superficial corneal diseases. AB - We performed phototherapeutic keratectomy (PTK) in seven patients (nine eyes) with superficial corneal disease such as band keratopathy (one patient), Reis Buckler's dystrophy (one patient, two eyes), granular dystrophy (two patients, three eyes), recurrent granular dystrophy (one patient), postinfection scar (one patient), and corneal scarring after pterygium removal (one patient). All patients received PTK after topical anesthesia with Pontocaine 0.5% and underwent epithelial removal with a surgical blade. We used methylcellulose 1.0% as a surface modulator before laser ablation. Focal ablation of the central cornea with an ablation zone of 5 mm was performed routinely in most eyes and a smoothing technique was applied only in two eyes. All patients were followed for more than 9 months. Uncorrected and corrected visual acuity were significantly improved in six patients (8 eyes) and a mild hyperopic shift occurred in all eyes that received PTK centrally. Mild to moderate corneal haze appeared in these corneas during the first few months after surgery. Some patients avoided the need for keratoplasty. No significant complications occurred after PTK except recurrence of granular deposits in one case of granular dystrophy. We think that PTK with the 193-nanometer excimer laser is indicated in the treatment of some superficial corneal disorders. PMID- 8499360 TI - Bilateral simultaneous myopic PRK as experienced by an ophthalmologist. AB - We have been performing excimer laser photorefractive keratectomy (PRK) and phototherapeutic keratectomy (PTK) since November 1991. As of August 1992, we had done 83 PRKs, of which 28 were bilateral, including two patients who had just 3 days separation between procedures. The majority of our patients requested PRK because of contact lens intolerance in Hong Kong's dusty environment. Some requested bilateral surgery at the same operative session to avoid anisometropia without their contact lenses, as well as to endure only one laser surgery with its attendant discomfort. As the bilateral approach became a routine part of our laser practice, many patients who had opted for unilateral procedures stated that, had they been able to take a little more time off, they also would have preferred this technique. PMID- 8499361 TI - Phototorefractive keratectomy--a personal insight. AB - The author, aged 48, an active Summit excimer laser user, had his own right myopic eye corrected by photorefractive keratectomy. Surgery was performed on April 17, 1992, to an eye with a spherical equivalent of -4.50 D, with a postoperative refraction goal of -0.75. This personal experience has allowed for some practical insights which are helpful in advising patients on expectations after PRK. PMID- 8499362 TI - PRK using an absorbing cell delivery system for correction of myopia from 4 to 26 D in 3251 eyes. AB - An ophthalmic laser unit with a Lambda-Physik LPX excimer emitting 193 nm and a unique beam shaping system was designed at the Complex "Eye Microsurgery." An absorbing cell, used as the main element of the delivery system, allowed us to obtain a precise profile of the laser energy density on the patient's cornea, smoothly changing the corneal refraction with each shot in the whole ablation area. The absorbing cell also allowed for varying the shape of distribution of radiation energy density depending on the patient's corneal shape. We performed more than 7000 photorefractive keratectomy laser operations in myopic patients, and report results in 3251 myopic eyes (approximately 46%) from -4.00 to -26.00 D, up to 4 years after surgery. In eyes with myopia greater than 6.00 D, emmetropia was obtained in 48% of cases; 42% had a residual mild myopia within 5.00 D; and 12% had a residual myopia more than 3.00 D. The corneal haze disappeared in 48.8% of cases; haze not affecting the visual acuity remained in 39%; and clinically significant haze remained in 12.2%. These eyes required a powerful medication or repeated PRK. After surgery, 87.7% of patients needed no spectacle correction. Excimer laser PRK with the use of the forming system efficiently corrects high myopia. PMID- 8499363 TI - The erodible mask in photorefractive keratectomy for myopia and astigmatism. AB - This paper reports a new approach for performing photorefractive keratectomy (PRK) that uses an erodible mask to control shape transfer processes. The advantages of this technique, when compared to conventional PRK performed with mechanical diaphragm, are 1) the possibility of transferring almost any shape onto corneal surface; 2) a smoother corneal surface following photoablation; 3) easier eye fixation; and 4) a controlled humidified environment over ablation zone. We report our experimental study on scanning electron microscopy of polymethylmethacrylate (PMMA) plates ablated using conventional technique versus erodible mask technique; the results showed a smoother surface in the PMMA plate ablated using the erodible mask. We also report our preliminary clinical results of four eyes treated for the correction of myopia combined with astigmatism. Myopia ranged from -2.00 to -10.00 D, and astigmatism ranged from -1.50 to -2.50 D. Three months after surgery, all four eyes were within +/- 1.00 D of myopic attempted correction, but astigmatism was completely corrected only in one eye. No complications or scarring have been reported. We believe the erodible mask could be effective in the correction of myopia and myopic astigmatism, but further improvements are necessary to allow easier alignment of the mask over the eye. All commonly available excimer laser devices produce photorefractive keratectomy as a concentric ablation of the corneal stroma, deeper in the center than in the peripheral part; this is produced by means of an iris or diaphragm which, depending on the type of laser, progressively opens or closes, allowing a greater laser beam delivery in the center.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499364 TI - Keratomileusis for myopia with the excimer laser (Buratto technique): short-term results. AB - We present a prospective clinical study based on the results of 150 consecutive cases of myopic intrastromal keratomileusis cases using the Exci-Med UV200 193 nm excimer laser 193-nanometer (Summit Technology, Inc, Waltham, Mass) to reduce high myopia. The mean and standard deviation of the follow up considered was 3.13 +/- 1.12. The mean preoperative spheroequivalent was -18.96 +/- 3.70 D and -2.32 +/- 2.36 D postoperatively. One hundred twenty-eight eyes (85.3%) were within +/- 1.00 D from the intended correction. In a majority of cases the best spectacle corrected visual acuity was unchanged or improved. No cases of intraoperative complications were observed; postoperative complications are reported. The Buratto technique to correct or reduce high myopia is efficient and safe, while the predictability is satisfactory. PMID- 8499365 TI - Holmium:YAG laser thermokeratoplasty for hyperopia and astigmatism: an overview. AB - The holmium:YAG laser can be used to perform corneal collagen shrinkage and treat refractive errors. Studies are underway for the treatment of hyperopia by shrinking collagen in the peripheral cornea, which produces central and paracentral steepening. There is initial overcorrection followed by a regression of effect postoperatively, which appears to stabilize 4 to 6 months postoperatively. Refinement of current nomograms and definition of the amount of expected regression will enhance its accuracy. The holmium:YAG laser may be superior to radial thermokeratoplasty with a hot needle. Nearly 100 years ago, Lans was the first to report that heating of the cornea could induce collagen shrinkage with resultant corneal curvature changes. Various collagen shrinkage procedures have evolved since then. To date, the most well-known form of collagen shrinkage involves the hot needle and a technique developed by Fyodorov to do radial thermokeratoplasty for hyperopia. This article will review the current state of holmium:YAG laser technology and the advantages it may provide over radial thermokeratoplasty. PMID- 8499366 TI - Excimer laser photoablation of primary familial amyloidosis of the cornea. AB - A 31-year old female underwent lamellar keratoplasty for the treatment of bilateral primary familial amyloidosis of the cornea in 1983 (OS), 1986 (OD), and 1989 (OS). The lesions recurred bilaterally and visual acuity in 1992 was 20/400 in each eye. After debridement of essentially all corneal epithelium, the entire cornea of the left eye was treated with excimer laser phototherapeutic keratectomy (PTK). One month postoperatively, visual acuity was 20/50 and the corneal surface appeared smooth and clear with no evidence of recurrence. Four months postoperatively, the patient continued to be free of recurrence. PMID- 8499367 TI - Photorefractive keratectomy for myopia: six month results of 193 eyes. PMID- 8499368 TI - Bibliography for laser corneal surgery. PMID- 8499369 TI - Photorefractive keratectomy for myopia: preliminary results in 147 eyes. AB - Excimer photorefractive keratectomy (PRK) was performed on 100 consecutive patients (147 eyes) for the correction of myopia. The follow up period ranged from 3 to 16 months (mean, 8). Preoperative myopia ranged from -1.75 to -8.75 D (mean -3.90 D). Patients were divided into three groups for analysis based upon their degree of preoperative myopia: mild (< or = 2.90 D), moderate (-3.00 to 5.90 D), and severe (> or = -6.00 D). Uncorrected visual acuity was 20/40 or better in 88.4% (130/147) overall; 97% of mild, 91% of moderate, and 68% of severely myopic patients. Preoperative astigmatism remained the primary cause of reduced uncorrected visual acuity. Postoperatively, 68% of patients overall had a spherical equivalent refraction within +/- 1.00 D. The majority of treated corneas had trace (53%) to mild (29%) subepithelial haze. One patient with severe myopia developed significant subepithelial opacification postoperatively with partial regression and loss of one line of best spectacle corrected visual acuity. PMID- 8499370 TI - Corneal topographic analysis of photorefractive keratectomy in 175 myopic eyes. AB - Videokeratography is a useful method for postoperative evaluation of photorefractive keratectomy (PRK). The aim of this study was to evaluate the percentage of decentration, the relationship between decentration relative to the corneal apex, postoperative astigmatism, and the relationship between decentration and best corrected Snellen visual acuity. Using the TMS-1 videokeratoscope we analyzed the corneal topography of 175 myopic eyes treated with PRKs ranging between -1.30 D and -15.90 D, performed using the Summit UV200 193-nanometer excimer laser, before and at least 6 months after the procedure. Concerning centration, 122 eyes (75%) were centered within 0.5 mm and 53 eyes (30.3%) were decentered more than 0.5 mm, with nine eyes (5.1%) being decentered more than 1 mm. There was a correlation between best spectacle corrected visual acuity and the amount of decentration. The higher attempted corrections showed greater amounts of decentration. Postoperative induced astigmatism was greater in the group with the highest decentration (1.81 +/- 2.64 D) than in the one with lower decentration (0.09 +/- 0.50 D). The most severe complication induced by a decentered PRK is an increase of postoperative astigmatism. PMID- 8499371 TI - Effect of centering excimer laser PRK on refractive results: a corneal topography study. AB - Computer-assisted analysis of corneal topography, using an EyeSys Corneal Analysis System instrument, was performed on 20 normally sighted human eyes that underwent excimer laser photorefractive keratectomy (PRK) to correct high myopia from 6.00 to 17.00 D (mean 10.90 +/- .SD 2.90 D). Ablations utilized one or two zones, at a single time, with an ExciMed UV200 193-nanometer excimer laser (Summit Technology, Inc, Waltham, Mass). Mean follow up was 28.9 weeks (+/- 13). Decentered treatment caused an average error of 1.06 D in the attempted refractive result. PMID- 8499372 TI - Excimer laser photorefractive keratectomy to correct residual myopia after radial keratotomy. AB - We performed excimer laser photorefractive keratectomy (PRK) on 10 undercorrected myopic eyes of nine patients with residual myopia, (N = 2, > -6.00 D, N = 8, 2.00 -5.75 D) after radial keratotomy. Patients' mean age was 32.1 years. The time interval between radial keratotomy and PRK ranged from 12 to 90 months (mean 35). All patients after PRK were followed 9 months or more. Nine months following PRK, uncorrected visual acuity ranged from 20/25 to 20/50 in all cases. Mean manifest refractive changed from -5.06 D preoperatively to -0.66 D after surgery, and the mean keratometric power changed from 41.40 +/- 1.56 D to 38.48 +/- 1.77 D. Persistent corneal haze (grade 1) was noted only in one eye at 9 months and no other significant complications occurred. Therefore, excimer laser PRK appears to be a good method to correct residual myopia after radial keratotomy. PMID- 8499373 TI - Correction of myopic anisometropia with photorefractive keratectomy in 15 eyes. AB - Photorefractive keratectomy (PRK) was performed to correct postoperative myopia and anisometropia in 15 eyes: seven eyes following IOL implantation, six eyes after radial keratotomy, and two eyes after corneal transplantation. The results for the first IOL group were similar to simple PRK in cases of myopia. The RK group showed a tendency for overcorrection. Penetrating keratoplasty eyes showed, after 6 months, changing and moderate haze. PMID- 8499374 TI - Photorefractive keratectomy for myopia from 6.00 D to 10.00 D. AB - Surgical correction of mild and high myopia using excimer laser photorefractive keratectomy (PRK) remains controversial. We present a retrospective study of 40 consecutive PRK procedures performed to reduce myopia ranging from -6.00 D to 10.00 D. Postoperative follow up was 24 months. The mean preoperative spheroequivalent refraction was -8.12 +/- 1.52 D; postoperatively it was -2.31 +/ 1.25 D. In 26 of 40 eyes (65%) we observed a regression of the refraction effect after 6 months. In 85% of eyes a persistent corneal haze (+1 grading) was observed at the end of follow up. Photorefractive keratectomy to correct or reduce mild or high myopia is simple and safe but had poor predictability and significant refractive regression in this series. PMID- 8499375 TI - Multistep photorefractive keratectomy for high myopia. AB - Nineteen human myopic eyes exceeding -8.00 D underwent multi-step excimer laser photorefractive keratectomy (PRK) with 6-month follow up. We performed two or three step PRK at the same time according to the amount of myopia present. The preoperative refraction ranged from -8.87 D to -16.99 D (mean -12.28 D). The mean attempted correction was 7.83 D. Six months after surgery, the mean refraction was -2.23 D. Keratometry demonstrated stable flattening of the cornea, and pachometry showed central cornea thinning. Seventeen eyes had clear or trace corneal haze. Above results showed multi-step PRK is a safe and relatively efficient procedure for correction of high myopia, but long-term follow up will be necessary to determine the stability of this procedure. PMID- 8499376 TI - Randomized study of single vs double exposure in myopic PRK. AB - Multizone PRK has been suggested to increase the predictability of higher myopic corrections. The technique consists of dividing the intended correction between two or three different concentric ablation zones, achieving less depth and a smoother ablation profile. We randomized 24 eyes with refractions between -6.00 and -9.00 D for single or double ablation-zone PRK. At 1 year no significant difference in refraction and complications were found between the two treatments. The multizone PRK technique may be safely employed to reduce the maximum central depth of the keratectomy in high myopics. PMID- 8499377 TI - Clinical experience of two-step photorefractive keratectomy in 19 eyes with high myopia. AB - The maximum myopic correction with one-step ablation in excimer laser photorefractive keratectomy (PRK) using the ExciMed UV200 LA 193-nanometer excimer laser (Summit Technology, Inc, Waltham, Mass,) is only up to 6.00 D because of a fixed computer program. We performed a simultaneous two-step PRK procedure for nearly full correction on 19 eyes of 19 patients with myopia ranging from -8.00 to -13.50 D. We clinically evaluated the results of this modified technique at 6 months, or more, after surgery. In the two-step PRK procedure, we attempted in the first-step of a maximum correction of -6.00 D (including up to -7.50 D) with 4.5-millimeter ablation zone. The second step was performed immediately thereafter to correct the remaining myopia with a 5.0 millimeter diameter ablation. Mean preoperative manifest refraction was -9.77, D and mean postoperative manifest refraction was -1.09 D at 6 months after two-step PRK. Uncorrected visual acuity of 20/40 or better was achieved in 74% of 19 eyes (two were amblyopic eyes). Corneal subepithelial haze was trace or +1 in all cases at 3 months, but faded out after 3 months. Transient intraocular pressure elevation occurred in one case. No other significant complications developed. Long-term follow up will be required to evaluate the results of two-step PRK. PMID- 8499378 TI - Photorefractive keratectomy for myopia: single vs double-zone treatment in 166 eyes. AB - We studied 58 single-zone and 58 double-zone treatments; attempted correction ranged between 6.50 and 10.00 D. There were no significant differences in the age or sex in the two groups. All the eyes received the same topical corticosteroid therapy. Refractive outcome showed a greater overcorrection in the double-zone than in the single-zone treatments, but the difference was not statistically significant (F = 3.17, p = 0.07). The refractive error shifted toward myopia significantly over time (F = 561.34, p < 0.0001). In the first-, third- and sixth month follow up, the mean refractive error was +2.39 (+/- SD) +/- 1.94, +0.45 +/- 1.54, and -0.60 +/- 1.50 D in the single-zone treatments, while in the double zone ones they were +1.95 +/- 2.49, +0.87 +/- 2.85 and +1.34 +/- 2.57 D, respectively. The Student's T test demonstrated a statistically significant difference of refractive outcome between the two groups only at 6 months (T = 3.788, p < 0.0001). Corneal haze decreased during follow up (F = 123.38, p < 0.0001) and was more severe in the single-zone than in the double-zone treatments (F = 9.28, p = 0.002). The Student's T test showed a significant difference at 6 months (T = 2.877, p = 0.006). The double-zone procedure appeared to be safer than the single-zone, but a longer follow up period and a greater number of treatments are required to draw final conclusions. PMID- 8499379 TI - Visual, refractive, and patient satisfaction results following bilateral photorefractive keratectomy for myopia. AB - Reports of the visual, refractive, and patient satisfaction results after photorefractive keratectomy (PRK) are now becoming available. The visual, refractive, and patient satisfaction results of 52 patients after bilateral excimer laser photorefractive keratectomy for myopia were studied. Patient satisfaction was measured using a five-part questionnaire. Initial patients obtained an overcorrection which necessitated adjusting the programmed correction to 75% of targeted correction. PMID- 8499380 TI - Efficacy of corticosteroids in reversing regression after myopic photorefractive keratectomy. AB - Topical corticosteroids are given commonly after photorefractive keratectomy (PRK). We present six eyes treated for correction of myopia ranging between -6.00 and -8.00 D, to whom corticosteroid drops were given and then suspended. Each eye had an increase in myopia with a mean of 2.00 D (range 1.00 to 3.50 D). All were then treated with topical dexamethasone (0.1%) four times per day for at least 15 days, and all showed decreases in myopia with partial or complete recovery of the intended correction (mean: 1.625 D; range 1.00 to 3.50 D). All of these refractive variations were documented by corneal topography. In one eye, refractive and topographic variations were detected by 3 days after corticosteroid treatment was initiated and they increased for 15 days. We believe corticosteroids can modulate refractive changes after PRK. PMID- 8499381 TI - Effect of corticosteroids in postoperative care following photorefractive keratectomies. AB - Since the start of photorefractive keratectomy (PRK) Seiler has recommended the use of topical corticosteroids during the first 3 months after surgery. The rationale for this treatment was to diminish the inflammatory reaction as well as to control the keratocytes from producing collagen and creating scars. Our knowledge of corneal wound healing in general, and after PRK in particular, is very limited and the action of corticosteroids is still unclear. Corticosteroids, when given in comparatively large topical doses, create problems. Between 15 and 30% of patients are corticosteroid responders with increased intraocular pressure. This is a threat to the eye, and also a burden for the doctor as intraocular pressure has to be checked during the treatment. The risk for cataract formation after longer periods of topically administered corticosteroids also has been discussed. In order to decrease the rise in intraocular pressure, FML has been used in place of dexamethasone. During the 4 years follow up after PRK it has been reported that a number of patients do not regress or get a scar formation if they have not used corticosteroids in the postoperative period. The reasons to avoid topical corticosteroids in some patients are a misunderstanding of their instructions, or those who have had a history of herpes infection or glaucoma. A double-masked study of the effects of corticosteroids after PRK was performed by Gartry, et al in a small group of patients. After 6 months, the results revealed that there were no differences between the corticosteroid and the non-corticosteroid group. However, the standard deviation was high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499382 TI - Course of subepithelial corneal haze over 18 months after photorefractive keratectomy for myopia [corrected]. AB - This study of 285 myopic eyes treated with photorefractive keratectomy (PRK), with a maximum follow up of 18 months, was designed to analyze the clinical subepithelial significance of corneal haze after excimer laser PRK. The treatment parameters included an ablation zone diameter from 3.6 to 5 mm, ablation rate from 0.22 to 0.25 micron pulse, fluence of 180 mJ/cm2, and frequency of 10 Hz. All patients used a standard topical corticosteroid regimen. A statistical analysis of the subjective haze grading showed a maximum at 3 months (mean grading, 1.03) and a decrease to 0.38 at 18 months. Haze is statistically greater with higher amounts of treatment (p = .003 between 2.00 D and 3.00 D groups, p = .0002 between 2.00 D and 6.00 D groups). In males (p = .0004), and in ablations less than 4.5 mm diameter (p = .0002) but no difference was found related to age. The overall frequency of clinically significant haze was 11.5% with a mean age of 35.1 years and a mean attempted correction of -5.71 D. This frequency increased to 24% in the 6.20 D to 9.90 D group and 38.6% in the 4.4 mm and less group, and it decreased to 8.6% in the 1.00 D to 6.00 D group and 6.6% in the 4.5 and 5 mm group. All patients with significant haze gave a history of discontinued use of corticosteroids. We suggest there exists a significant haze risk group in which the absence of steroid or discontinuation of corticosteroids will lead to significant haze. PMID- 8499383 TI - Contrast sensitivity under photopic conditions in photorefractive keratectomy: a preliminary study. PMID- 8499384 TI - Halos--a problem for all myopes? A comparison between spectacles, contact lenses, and photorefractive keratectomy. AB - After photorefractive keratectomy (PRK) using excimer lasers (193 nm) many patients report the presence of halos around light sources at night. However, halos are not unique to PRK patients, as they are a common observation in myopic contact lens wearers. We present an objective measurement of the halos using a computerized technique. The patient fixated on a red cross within a white circle in the center of a video monitor which served as the halo source. The screen surrounding the circle was not illuminated. The operator controlled the movement of the white spot and moved the spot toward the halo source until the subject indicated when the cursor was at the outer parameter of the halo. Measurements were made at 30 degree intervals around the halo source and expressed as square degrees. The study found that spectacles, soft contact lenses, and excimer laser surgery were superior to hard contact lenses in terms of the size of the halo. A mean value of 2.51 square degrees was obtained for spectacles wearers compared with 3.18 square degrees for soft contact lenses, 3.14 square degrees for excimer laser patients with 4-millimeter ablation zone, 2.76 square degrees for excimer laser patients with a 5-millimeter ablation zone, and 89.5 square degrees for hard contact lenses. It appears that this device is very useful for measuring the halo size after excimer laser PRK. We concluded that halos were not a problem for our patients after excimer laser photorefractive keratectomy. PMID- 8499385 TI - Phototherapeutic keratectomy: long-term results in 166 eyes. AB - One hundred sixty-six eyes with corneal disease were treated with the excimer laser in order to ablate opacities, irregularities, or to improve wound healing. Postoperative follow up time was 15 months (range 6 to 28 months). An individual goal was set for each patient and 84% achieved the goal. The visual acuity change is given for each subgroup. Phototherapeutic keratectomy (PTK) was shown to be an advantageous surgical method, where the success is in the careful preoperative evaluation. One problem with the technique is the induced hyperopia. PMID- 8499386 TI - Philosophy and technique for excimer laser phototherapeutic keratectomy. AB - Phototherapeutic keratectomy (PTK) with the excimer laser has been shown to be effective in removing anterior corneal pathology and smoothing surface irregularities. Blocking agents are important in PTK. The techniques we present seek to balance therapeutic effect and refractive error change. Successful PTK depends on thorough preoperative assessment and attention to intraoperative detail. Clinical research has demonstrated that the excimer laser is an effective tool, not only for correcting myopic refractive errors, but also for treating various types of anterior corneal pathology. We present our PTK techniques that reflect recent refinements. PMID- 8499387 TI - Phototherapeutic keratectomy in corneal diseases. AB - We present our clinical strategy to treat corneal diseases with the excimer laser. Nine eyes with recurrent erosion after trauma, three eyes with band keratopathy, and one eye with secondary crystalline deposits and a leukoma adherens after perforating injury underwent excimer laser phototherapeutic keratectomy (PTK). The patients with recurrent erosion had at least six episodes in the 12 months, the other patients suffered from severe pain. The recurrent erosions were treated with 15 pulses (193 nm, 180 mJ/cm2, 10 Hz) after removing the epithelium. There was only one new episode within 6 months after treatment in a patient who failed to follow the postoperative therapeutic regimen. In the patients with band keratopathy we removed the calcium deposits mechanically and then used masking fluids to obtain a smooth surface. The crystalline deposits in the patient with leukoma adherens could be removed but recurred after 4 months; the patient still suffered from glare. PMID- 8499388 TI - Phototherapeutic keratectomy: strategies and results in 12 eyes. AB - As part of a multicenter study of excimer laser procedures, we performed phototherapeutic keratectomy (PTK) on 12 eyes in 11 patients. Three eyes had superficial corneal scarring, two Salzmann's degeneration, two Reis-Buckler's dystrophy; and one each with recurrent lattice dystrophy in a corneal graft, band keratopathy, recurrent erosion syndrome, after pterygium scarring, and contact lens related keratopathy. Indications for treatment included poor visual acuity, severe glare symptoms, ocular surface discomfort, recurrent erosions, and monocular diplopia. Follow up ranged from 1 to 4 months. Best spectacle corrected visual acuity improved in ten eyes with no eyes suffering loss of best spectacle corrected visual acuity. A hyperopic refractive shift was found in eight of 12 treated eyes. Corneal surface regularity improved in six of 12 eyes and worsened in one eye as measured by computerized corneal topographic analysis. Ten patients (11 eyes) noted improvement in their visual perception and subjective symptoms. We review various strategies of phototherapeutic keratectomy designed to treat particular corneal disorders: patient selection criteria to optimize clinical outcome are reviewed as well. PMID- 8499389 TI - Phototherapeutic keratectomy for Reis-Buckler's dystrophy. AB - Reis-Buckler's dystrophy has been a difficult management problem with generally poor long-term results from the conventional treatment techniques of penetrating and lamellar keratoplasty. Phototherapeutic keratectomy (PTK) is now the standard method of managing this anterior corneal disease when intervention is required. We have treated nine eyes with Reis-Buckler's dystrophy, including two in whom previous penetrating keratoplasty had been performed. All of our patients achieved substantial visual improvement from an average visual acuity of 6/60 to 6/9, and all had complete cessation of recurrent erosions. PMID- 8499390 TI - Photorefractive keratectomy in 472 eyes. AB - Between July 1990 and July 1992, 472 eyes were treated with photorefractive keratectomy (PRK) using the ExciMed UV200 193-nanometer excimer laser (Summit Technology, Inc, Waltham, Mass). The sphere equivalent refractions ranged between -1.25 and -9.60 D, with less than 1.25 D of astigmatism. Eyes with refractive error up to -6.00 D were treated with a spherical ablation, as determined by the surgeon's decision and the algorithm built into the laser software. In this group, 92% had a refraction within 1.00 D of intended correction. Eyes with more than -6.00 D of myopia were treated with a dual-zone procedure, using a nomogram developed by the author. After 6 months, 45% of eyes had a refraction within +/- 1.00 D, and 84% were within +/- 2.00 D of emmetropia. Excimer PRK up to -6.00 D is safe and predictable; above -6.00 D it is less predictable. PMID- 8499391 TI - Toward more reliable printed stereo. AB - The printing and displaying of pictures as stereo pairs has been widespread for a long time, and yet it is still a common experience that published stereo pairs can be difficult to fuse, can cause eye-strain, can give a false or confusing sense of depth, and are sometimes even front-to-back inverted. This short note is intended to describe simply how to minimize or eliminate these common problems. The method is to match the focus and the convergence cues at the viewer's eyes, and to calculate the geometry reliably and accurately to better than the crude approximation now almost universally in use. Experience has shown that stereo so printed is acceptable to many people who normally cannot use the technique, and that a more secure sense of positioning and depth can be achieved. PMID- 8499392 TI - Pharmacophoric pattern matching in files of three-dimensional chemical structures: characterization and use of generalized torsion angle screens. AB - This paper describes the use of generalized torsion angles for the screening of conformational searches in databases of three-dimensional chemical structures. A generalized torsion angle is defined as the dihedral angle between two vectors, A1-A2 and A3-A4, in which none, some, or all of the vectors A1-A2, A2-A3, and A3 A4 correspond to formal chemical bonds. The screens consist of a set of four atoms together with an associated angular range, and are identified by a statistical analysis of the frequencies of occurrence of these features in the Cambridge Structural Database. These frequencies are discussed, and the effectiveness of the screens is demonstrated by an extensive series of searches for representative pharmacophoric patterns. PMID- 8499393 TI - A new approach to the automatic identification of candidates for ligand receptor sites in proteins: (I). Search for pocket regions. AB - The work presented here is aimed at the topographical analysis of localized regions of receptor proteins leading to the identification of pocket areas (superficial depressions or internal cavities), which may play the role of receptor sites. An algorithm is described that yields complete information about the position of each cavity or superficial depression relative to any point of the protein molecules, as well as detailed information on the atoms constituting it. The applicability of this algorithm to the automatic identification of candidate receptor sites in a receptor protein is also discussed using the typical receptor structure dihydrofolate reductase-methotrexate complex. PMID- 8499394 TI - Reproduction of correct electrostatic field by charges and dipoles on a closed surface. AB - A general algorithm based on the Green function theorem has been developed to correctly reproduce electrostatic fields inside a closed space by point charges and point dipoles on the surface surrounding the space. For actual computations, limited numbers of point charges, including charge pairs replacing point dipoles, are enough to approximate the inner fields. As examples, reaction fields were reproduced by the current surface charges and dipoles for the dielectric models, where a monopole, dipole, or quadrupole was individually set at the center in a vacuum sphere surrounded by high dielectric continuum. The potentials due to those reaction fields agree well with the analytical ones. As an application of this method to the analysis of the electronic structure of the active site of a protein, a combination of the continuum dielectric model and ab initio molecular orbital calculation was carried out. Other applications to molecular dynamics and quantum mechanical calculations are also discussed. PMID- 8499395 TI - Volume-rendering representations of ab initio electron densities. AB - Many molecular properties are three-dimensional scalar fields, making the representation of their values throughout the molecular volume a four-dimensional problem. Volume rendering offers a means of graphically displaying the value of a property throughout a volume. In this paper we present the result of an interface of the ab initio electronic structure program. GAUSSIAN 85, and the interactive volume-rendering program, VOXEL-VIEW PLUS, and its initial application: the representation of electron densities for acetylene and difluoroacetylene, and transition structures for the corresponding vinylidene isomerizations. PMID- 8499396 TI - MoG: molecular graphics software for the Commodore Amiga. AB - As recently described by Garavelli, the Commodore Amiga 3000 computer is "nearly ideal" for desktop molecular modeling. The chief drawback to date, has been the lack of suitable software. This paper describes a new desktop molecular modeling package, MoG, which is suitable for both research and educational use. The speed of the Amiga 3000 means that MoG competes very favorably with software on IBM-PC machines, and its graphics capabilities allow excellent space-filling representations. The availability of cheap software-compatible home-computer versions of the Amiga places interactive molecular graphics within the reach of many senior high-school students, undergraduates and graduate students. PMID- 8499397 TI - Excretion of thromboxane metabolites in healthy women after cessation of smoking. AB - Cigarette smokers, but not former smokers, excrete more thromboxane A2 (TxA2) metabolites in the urine than do lifelong nonsmokers, which suggests chronic activation of their platelets. To further characterize the effect elicited by smoking on platelet function, we followed the change in urinary excretion of the 2,3-dinor (Tx-M) and 11-dehydro (dTx) metabolites of TxA2, analyzed by gas chromatography/mass spectrometry and radioimmunoassay, respectively, in eight healthy women who quit habitual smoking and compared it with the recovery of these metabolites after a single dose of acetylsalicylic acid (ASA). Tx-M and dTx before cessation of smoking were approximately 550 and 600 pg/mg creatinine, respectively. Within 3 days after quitting smoking, Tx-M and dTx had dropped to stable levels of approximately 300 and 350 pg/mg, respectively. The rates of change in excretion of Tx-M and dTx after smoking cessation were more rapid (p < 0.02 and 0.02, respectively) than those observed during the recovery of platelet function after a single dose of ASA. The excretion of 2,3-dinor-6-keto prostaglandin F1 alpha, a metabolite of prostacyclin, was not affected by smoking cessation. We conclude that cigarette smoking elicits an increase in platelet activity in the absence of vascular injury. This increase is reversible within the life span of the platelets. PMID- 8499398 TI - Plasma fibrinogen and its correlates in Japanese and US population samples. AB - In a preliminary 1987 study, we reported that the plasma fibrinogen level was significantly higher in Caucasian American men than Japanese men. To confirm this finding, we used data from 1,020 Japanese men and women in a 1989-1991 Akita, Japan, population study and from > 15,000 men and women from the 1986-1989 Atherosclerosis Risk in Communities (ARIC) Study. To examine further the correlates of plasma fibrinogen level, subsamples of nonsmoking Akita Japanese (n = 150) and Minneapolis Caucasians (n = 150) were also studied separately in 1990. Compared with the Japanese in the Akita study, Caucasians and African Americans in ARIC had a 23-40 mg/dL higher age-adjusted fibrinogen level for men and a 25 67 mg/dL higher level for women. In the subsample, the mean plasma fibrinogen value was 288 mg/dL in Caucasian men and 248 mg/dL in Japanese men (test for difference: p < 0.001). Women showed a similar racial difference: 300 mg/dL in Caucasians and 257 mg/dL in Japanese (p < 0.001). There were weak but positive correlations of plasma fibrinogen with age and body mass index and weak inverse correlations with alcohol intake, high density lipoprotein cholesterol, and triglycerides in most of the sex-race groups. For women, plasma fibrinogen was positively associated with menopause and inversely associated with the use of hormone replacement therapy. Total fish intake was inversely associated with plasma fibrinogen in all sex-race groups, and the association was statistically significant for Caucasian men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499399 TI - Plasma fibrinogen level is not elevated in young adults from families with premature ischemic heart disease. AB - Several epidemiological studies have found that the plasma fibrinogen level is a risk factor for ischemic heart disease (IHD), similar in importance to the serum cholesterol level. A family history of IHD is also a significant risk factor for IHD, statistically independent of the serum cholesterol level. Whether the familial risk for IHD is related to genetic control of the fibrinogen level is unknown. Estimates of the genetic contribution to the variance in plasma fibrinogen levels vary markedly. We previously found elevated levels of cholesterol and factor VII in young subjects with a familial history of premature IHD. In the present study we chose to measure fibrinogen, factor VII antigen, and total cholesterol levels in 43 asymptomatic first-degree relatives (< 50 years old) of patients with premature IHD and in 43 age- and sex-matched asymptomatic young adults at low risk of IHD. No subjects in either group were smokers. The mean plasma fibrinogen level of the high-risk group (259 mg/dL) did not differ significantly from that of the low-risk group (250 mg/dL; p > 0.4). In contrast, the high-risk group had significantly higher mean factor VII antigen (p < 0.001) and mean serum cholesterol (p < 0.0001) than the low-risk group. These data argue against the hypothesis that genetic determination of the plasma fibrinogen level is a common pathophysiological mechanism responsible for familial risk of IHD. PMID- 8499400 TI - Impaired chylomicron remnant clearance in familial combined hyperlipidemia. AB - Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test. The chylomicron remnant clearance (Sf < 1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05 +/- 12.84 hours x [mg/L]) compared with control subjects (25.1 +/- 5.4 hours x [mg/L]; p = 0.01). Postprandial lipoprotein particle size and composition in the Sf > 1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54 +/- 0.09 mmol/L) than in control subjects (0.89 +/- 0.05 mmol/L; p < 0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94 +/- 25 and 427 +/- 57 milliunits/mL, respectively) and control subjects (126 +/- 16 and 362 +/- 33 milliunits/mL, respectively). In FCH, a 54% reduction (p < 0.05) of plasma triglycerides to 2.63 +/- 0.41 mmol/L by drug treatment resulted in an enhanced, but not normalized, clearance of chylomicron remnants (39.4 +/- 6.0 hours x [mg/L]). Univariate regression analysis revealed that in FCH subjects the changes in fasting plasma apolipoprotein C-III concentrations after therapy were significantly associated with the changes in chylomicron remnant AUC-RP (r = 0.87; p = 0.02). Delayed elimination of atherogenic chylomicron remnants may contribute to the increased risk of premature atherosclerosis in FCH. PMID- 8499401 TI - Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects. AB - The relations of cholesteryl ester transfer protein (CETP) activity to the distribution of low density lipoproteins (LDLs) and high density lipoproteins (HDLs) were investigated in fasting plasma samples from 27 normolipidemic subjects. LDL and HDL subfractions were separated by electrophoresis on 20-160 g/L and 40-300 g/L polyacrylamide gradient gels, respectively. Subjects were subdivided into two groups according to their LDL pattern. Monodisperse patterns were characterized by the presence of a single LDL band, whereas polydisperse patterns were characterized by the presence of several LDL bands of different sizes. To investigate the influence of lipid transfers on LDL patterns, total plasma was incubated at 37 degrees C in the absence of lecithin:cholesterol acyltransferase (LCAT) activity. The incubation induced a progressive transformation of polydisperse patterns into monodisperse patterns. Under the same conditions, initially monodisperse patterns remained unchanged. Measurements of the rate of radiolabeled cholesteryl esters transferred from HDL3s to very low density lipoproteins (VLDLs) and LDLs revealed that subjects with a monodisperse LDL pattern presented a significantly higher plasma CETP activity than subjects with a polydisperse LDL pattern (301 +/- 85%/hr per milliliter versus 216 +/- 47%/hr per milliliter, respectively; p < 0.02). In addition, when total plasma was incubated for 24 hours at 37 degrees C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from HDLs to apolipoprotein B containing lipoproteins was greater in plasma with monodisperse LDL than in plasma with polydisperse LDL (0.23 +/- 0.06 versus 0.17 +/- 0.06, respectively; p < 0.02). These results indicated that in normolipidemic plasma, CETP could play an important role in determining the size distribution of LDL particles. The analysis of lipoprotein cholesterol distribution in the two groups of subjects sustained this hypothesis. Indeed, HDL cholesterol levels, the HDL:VLDL+LDL cholesterol ratio, and the esterified cholesterol:triglyceride ratio in HDL were significantly lower in plasma with the monodisperse LDL pattern than in plasma with the polydisperse LDL pattern (p < 0.01, p < 0.01, and p < 0.02, respectively). Plasma LCAT activity did not differ in the two groups. Plasma CETP activity correlated positively with the level of HDL3b (r = 0.542, p < 0.01) in the entire study population. Whereas plasma LCAT activity correlated negatively with the level of HDL2b (r = -0.455, p < 0.05) and positively with the levels of HDL2a (r = 0.475, p < 0.05) and HDL3a (r = 0.485, p < 0.05), no significant relation was observed with the level of HDL3b.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8499402 TI - Lipoprotein[a] as a risk factor for preclinical atherosclerosis. AB - Elevated mean levels of lipoprotein[a] (Lp[a]) have been associated with symptomatic cardiovascular diseases such as clinically manifest myocardial infarction (MI), coronary artery disease, restenosis of coronary artery vein grafts after bypass, and a family history of MI. Associations of Lp[a] with arterial wall thickening in asymptomatic individuals previously have not been addressed and are evaluated in this report among participants of the Atherosclerosis Risk in Communities (ARIC) Study. Intima-media wall thickening in the extracranial carotid arteries was assessed noninvasively with B-mode ultrasonography; Lp[a] was measured as its total protein component. Individuals with wall thickening > or = 90th percentile of the population maximum far-wall thickness were pair matched to participants < 75th percentile of wall thickness by race, gender, center, 10-year age group, and time of examination. These selection criteria yielded 492 matched pairs, with 395 white pairs and 97 black pairs. The mean Lp[a] protein level for all black participants was 174.6 micrograms/mL compared with 77.8 micrograms/mL for whites. Conditional logistic regression analysis for the association of Lp[a] with case-control status yielded a statistically significant prevalence odds ratio (OR) estimate of 1.49, based on a 1-SD difference in Lp[a] protein, after adjusting for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen, hypertension, and cigarette smoking. None of these risk factors significantly altered the OR, in agreement with reports that Lp[a] is unaffected by environmental influences. In addition, no differential effect of Lp[a] protein on case-control status (effect modification) was observed by race, gender, low density lipoprotein cholesterol, or fibrinogen in this population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499403 TI - Lipid transfer protein-mediated distribution of HDL-derived cholesteryl esters among plasma apo B-containing lipoprotein subpopulations. AB - The substrate specificity of lipid transfer protein has been examined in whole plasma in vitro by following the redistribution of high density lipoprotein (HDL) derived [3H]cholesteryl ester (CE) into apolipoprotein (apo) B-containing lipoproteins using density gradient ultracentrifugation. HDL-derived [3H]CEs were incubated with plasma or isolated lipoprotein classes (very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein [LDL] subpopulations from the HDL donor) with and without lipoprotein lipase for 0.5-6 hours at 37 degrees C. After incubation, lipoproteins were separated into 38 fractions after density gradient ultracentrifugation, and radioactivity, protein, and cholesterol were monitored across the profiles. These studies indicate that 1) lipid transfer protein activity varied among the individuals as well as within an individual; 2) the majority of the [3H]CE was associated with LDL; 3) in most individuals (71%), more HDL-derived [3H]CE distributed within the buoyant LDL density region; and 4) the distribution of HDL-derived [3H]CE was similar to the distribution of lipoprotein lipase-derived "remnant" particles within buoyant LDL. These in vitro studies support the hypothesis that HDL-derived [3H]CEs vary in their distribution among apo B-containing particles and that more HDL-derived [3H]CEs are transferred to lipoproteins within the buoyant LDL density range. Additional studies suggest that lipoprotein heterogeneity within this density range, such as the presence of remnant-like lipoproteins, may contribute to the selective distribution of HDL-derived [3H]CE into buoyant LDL. PMID- 8499405 TI - Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits. AB - To investigate whether exercise training can modulate endothelium-dependent vasorelaxation, male New Zealand White rabbits were divided into either control or training groups. The training animals were trained on a treadmill with a running speed of 0.88 km/hr on a 0 degree grade for 10-60 minutes/day, 5 days/week for 8 weeks. After exercise training, the resting heart rate was lowered (p < 0.05). At the end of the experiments, three vessel segments, i.e., the thoracic aortas, the pulmonary arteries, and the common carotid arteries, were isolated and precontracted with norepinephrine. Acetylcholine-stimulated endothelium-derived relaxing factor (EDRF) release was assessed by bioassay in the presence of indomethacin (10(-5) M). Basal release of EDRF was examined by the addition of hemoglobin. In addition, the relaxing responses of the thoracic aortas and pulmonary arteries to A23187, a calcium ionophore, and to sodium nitroprusside, a direct vasodilator of vascular smooth muscle, were compared between control and trained groups to further investigate possible underlying mechanisms. The results indicated that after exercise training 1) both the thoracic aorta and pulmonary artery, but not the carotid artery, became more sensitive to acetylcholine-induced vasorelaxation; 2) no significant differences in basal release of EDRF between control and trained rabbits were observed; and 3) there were no significant differences in the vascular responses to A23187 or sodium nitroprusside between the two groups. Our data suggest that exercise training may enhance endothelium-dependent vasodilation to acetylcholine via the stimulated EDRF release and that this elevated sensitivity to acetylcholine may not be caused by the alteration of the relaxing response in vascular smooth muscle. PMID- 8499404 TI - Increased production rates of LDL are common in individuals with low plasma levels of HDL cholesterol, independent of plasma triglyceride concentrations. AB - Reduced plasma levels of high density lipoprotein (HDL) cholesterol are associated with increased risk for coronary heart disease. Although plasma HDL levels are, in general, inversely related to plasma triglyceride (TG) concentrations, a small proportion of individuals with low HDL cholesterol concentrations have normal plasma TG levels. We wished to determine whether subjects with low plasma levels of HDL cholesterol could be characterized by common abnormalities of lipoprotein metabolism independent of plasma TGs. Therefore, we studied the metabolism of low density lipoprotein (LDL) apolipoprotein B (apo B) and HDL apolipoprotein A-I (apo A-I) in subjects with low plasma HDL cholesterol concentrations with or without hypertriglyceridemia. Nine subjects with low plasma HDL cholesterol levels and normal levels of plasma TGs and LDL cholesterol were studied. Autologous 131I-LDL and 125I-HDL were injected intravenously, and blood samples were collected for 2 weeks. LDL apo B and HDL apo A-I levels were measured by specific radioimmunoassays. Fractional catabolic rates (FCRs, pools per day) and production rates (PRs, milligrams/kilogram.day) for each apolipoprotein were determined. The results were compared with those obtained previously in nine subjects with low plasma HDL cholesterol levels and hypertriglyceridemia and in seven normal subjects. The normal subjects had an HDL apo A-I FCR (mean +/- SD) of 0.21 +/- 0.04. Despite large differences in plasma TG levels, the HDL apo A-I FCRs were similar in the low-HDL, normal-TG group (0.30 +/- 0.09) and the low-HDL, high-TG group (0.33 +/- 0.10), although only the latter value was significantly increased versus control subjects (p < 0.03). Increased apo A-I FCRs were associated with reduced HDL apo A-I levels in both groups of patients. Apo A-I PRs were similar in all groups. In contrast, LDL apo B PR was increased approximately 50% in the low-HDL, normal-TG group (19.3 +/- 6.6; p < 0.01) compared with normal subjects (12.5 +/- 2.6). There was a strong trend toward a greater LDL apo B PR in the low-HDL, high-TG group (17.6 +/- 4.5; p = 0.06 versus normal subjects) as well. LDL apo B FCRs were similar in all three groups. LDL apo B concentrations were also increased in the group with low HDL cholesterol and normal TG levels. Both groups with low HDL cholesterol levels had cholesterol-depleted LDL and HDL particles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8499406 TI - Platelet-associated factor XIII as a marker of platelet activation in patients with peripheral vascular disease. AB - In the past several years, monoclonal antibodies have been developed that distinguish between resting and activated platelets in vitro. These antibodies recognize epitopes expressed on membrane proteins or soluble proteins, such as factor XIIIa and thrombospondin, that bind only to activated platelets. We have used fluorescence flow cytometry to determine whether three such antibodies can detect platelet activation in patients with severe peripheral vascular disease (PVD). Using two activation-specific monoclonal antibodies and a polyclonal antiserum to factor XIII a-chain, we have examined the platelets from PVD patients, age-matched control subjects who were free of detectable PVD, and unmatched control subjects. Cells analyzed as platelets were identified by their light-scatter profile and their reactivity with monoclonal anti-glycoprotein Ib. The platelets of patients with PVD showed no increase in binding of activation dependent 1B3 (directed against a 180-kD membrane protein) compared with age matched control subjects (p = 0.780). Similarly, there was no difference between PVD patients and control subjects in activation-dependent CD63 expression. Conversely, the binding of anti-factor XIII a-chain was significantly higher than in the control groups (p < 0.001). These data suggest that the detection of soluble factors that bind to activated but not resting platelets may be of use in the detection of pathological in vivo platelet activation. PMID- 8499407 TI - Childhood consumption of dietary polyunsaturated fat lowers risk for coronary artery atherosclerosis in African green monkeys. AB - This study was designed to test the hypothesis that consumption of diets enriched in polyunsaturated fatty acids beginning at birth and continuing into young adulthood would lower the risk for atherosclerotic coronary heart disease early in life through their effects on plasma lipid and apolipoprotein concentrations while supporting good health and normal development. Accordingly, African green monkeys (n = 140) were raised on atherogenic diets (0.8 mg cholesterol per kcal) enriched with either saturated or n-6 polyunsaturated fatty acids. Breast milk from mothers fed the polyunsaturated fat diet became enriched in polyunsaturated fatty acids relative to the saturated group; thus, the period of nursing also reflected the dietary fatty acid shift. Age, gender, and dietary fat type independently affected plasma lipid and apolipoprotein concentrations. Age effects were similar for all lipid and lipoprotein variables; the concentrations were low immediately after birth, increased dramatically during the first 4-6 months of life, and then attained levels similar to those of adult animals by 2 years of age. Significant differences by gender were found such that females maintained lower total plasma cholesterol concentrations and higher high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations. Dietary fat effects were age dependent. Before weaning at 5 months of age, total plasma cholesterol and apoB concentrations were lower in animals consuming polyunsaturated fat, and this pattern was maintained into young adulthood. Lower concentrations of plasma triglycerides, HDL cholesterol, and apoA-I for polyunsaturated fat-fed animals were found only in the postweaning period (6-60 months of age). Since this pattern of response to dietary polyunsaturated fat in the juvenile animals was similar to that for adult animals fed these same diets in which there was less atherosclerosis and because subsequent studies have documented less coronary artery atherosclerosis in the polyunsaturated fat-fed juveniles, we conclude that early dietary intervention was beneficial in this group for lowering the risk of coronary artery atherosclerosis. The results in this primate model support the concept that intervention to modify coronary heart disease risk that is initiated early in childhood will have beneficial effects. PMID- 8499408 TI - Coronary arteriosclerosis in dogfish (Scyliorhinus canicula). An assessment of some potential risk factors. AB - Coronary myointimal lesions are described in the dogfish (Scyliorhinus canicula). These lesions are similar to those previously described in salmonids and are characterized by breaks in and disappearance of the inner elastic layer and intimal thickening as a result of inclusions of fibers and smooth muscle cells. Lesions are associated with all the branching points in the main subepicardial conal coronary arteries that supply the heart. Intimal thickenings were rare in other parts of these arteries. However, we found extensive lesions unassociated with branching points in two main intramyocardial ventricular arteries that supply the ventricular spongy myocardium. We carried out a statistical study of the incidence and severity of these intramyocardial lesions in relation to several potential risk factors. Intimal thickenings were present in 90.5% of the fish specimens and 40% of the histological sections. Sex, reproductive stage, plasma triacylglycerol, and cholesterol (total and related to high-density lipoproteins) were not significantly related to either the incidence or severity of lesions. Total fish length was significantly correlated with the lesion severity index (r = 0.33, p < 0.01). We also found significant differences in incidence related to the location of lesions. The middle areas of the intramyocardial branches, very close to the atrioventricular canal, were more affected than the cranial and caudal areas. The dorsal and ventral artery walls were also more affected than the lateral ones. The preferential location of the lesions in areas presumably subjected to mechanical stress because of a bifurcating bloodstream or the pulsatile flow throughout the atrioventricular canal suggests that coronary arteriosclerosis in dogfish is an age-related process, with hemodynamic factors playing a primary or secondary pathogenetic role. This disease seems not to be related to some factors suggested for salmonids, such as reproductive cycle, anadromous migration, river pollution, or plasma lipid concentration. PMID- 8499409 TI - Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study. AB - Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499410 TI - Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits. Possible mechanisms. AB - We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques. PMID- 8499411 TI - Microalbuminuria is a marker of left ventricular hypertrophy but not hyperinsulinemia in nondiabetic atherosclerotic patients. AB - Microalbuminuria predicts cardiovascular events in diabetic and nondiabetic patients. For a better understanding of the physiopathological importance of microalbuminuria in atherosclerotic disease, we evaluated the relation between urinary albumin excretion and arterial blood pressure, left ventricular mass, insulin, and lipid levels. The studies were conducted in patients with atherosclerotic peripheral vascular disease. Urinary albumin excretion (studied by nephelometry; an average of triplicate collections from 8 PM to 8 AM), causal blood pressure, echocardiographic left ventricular mass index and wall thickness, plasma immunoreactive insulin and C-peptide (both basally and after a 75-g oral glucose load), blood lipids, and fibrinogen were studied in eight normal subjects and 20 nonobese, nondiabetic male patients with angiographically documented atherosclerotic peripheral vascular disease and preserved renal function, 12 of whom were either hypertensive or on antihypertensive treatment. Eight patients were microalbuminuric (urinary albumin > 20 micrograms/min) and 12 were not. Ankle-arm index and calf and foot transcutaneous oxygen tension were reduced in comparison with normal control subjects but superimposable between the two patient groups to indicate a comparable clinical progression of the vascular disease. In the microalbuminuric subjects, left ventricular mass index was greater, interventricular septum was thicker, and cardiac hypertrophy was more frequent than in nonmicroalbuminuric patients. The prevalence of hypertension tended to be greater and systolic blood pressure values were higher in the presence of microalbuminuria. Overall, a highly significant relation existed between urinary albumin excretion and left ventricular mass. Systolic blood pressure was greater and a history of arterial hypertension was more frequent among microalbuminurics, whereas diastolic blood pressure values showed a statistically significant correlation with both variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499412 TI - Potentiation of the vasospastic response to angioplasty by pretreatment with fluoxetine. A study in the atherosclerotic rabbit. AB - There is evidence that angioplasty-induced vasospasm is mediated by serotonin (5 hydroxytryptamine [5-HT]) release from platelets. We tested the hypothesis that pretreatment of the atherosclerotic rabbit with fluoxetine, a platelet-uptake inhibitor of 5-HT, would reduce vasospasm after balloon angioplasty. Short-term administration of fluoxetine reduced platelet 5-HT uptake to 4% of baseline. Daily administration of fluoxetine for 7 days reduced whole-blood 5-HT levels to 28% of baseline. Thus, fluoxetine inhibited platelet 5-HT uptake in this model as predicted. Contrary to our expectations and despite the substantial reduction in whole-blood 5-HT levels, pretreatment with fluoxetine for 1 week resulted in augmentation of angioplasty-induced vasospasm in atherosclerotic rabbits. Intraperitoneal administration of fluoxetine produced vasoconstriction in normal rabbits that was augmented by 5-HT and not reversed with LY53857, a specific serotonin receptor antagonist. We postulate that this new observation is probably a result of the inhibition of the clearance mechanism for serotonin, with resultant enhancement of the effect of serotonin released by the activated platelets that are deposited on the vessel wall surface at the time of angioplasty. A direct effect of fluoxetine on serotonergic receptors is a second possible mechanism for the observed effect. PMID- 8499413 TI - Inhibition of smooth muscle cell proliferation and experimental angioplasty restenosis by beta-cyclodextrin tetradecasulfate. AB - Heparin inhibits smooth muscle cell proliferation in vitro, a property that makes it potentially useful in preventing restenosis after angioplasty. Its utility in this setting is limited by the inability to use high doses (secondary to anticoagulant effects) and the need for subcutaneous administration. We tested the ability of beta-cyclodextrin tetradecasulfate (CDT), a nonanticoagulant synthetic heparin mimic, to inhibit smooth muscle cell proliferation in vitro and tested its efficacy when orally administered for the prevention of angioplasty restenosis in a rabbit atherosclerosis model. Vascular smooth muscle cells were cultured from rabbit aortas by the explant technique. Passaged cells were plated at low density in microtiter plates in the presence or absence of varying concentrations of heparin or CDT in culture medium containing 10% fetal calf serum. Using both 3H-thymidine incorporation and total protein assays, both heparin and CDT caused a similar dose-dependent inhibition of proliferation. We next tested the effect of orally administered CDT in the prevention of restenosis in focal femoral artery arteriosclerotic lesions created in hypercholesterolemic New Zealand White rabbits by air-dessication endothelial injury and subsequent peripheral angioplasty. Animals were followed up for 1 month and were fed normal chow supplemented by tap water with or without CDT. In animals receiving the highest concentration of CDT (2 mg/mL drinking water), the percentage of arterial cross-sectional area with intimal hyperplasia decreased from 50.5 +/- 1.7% (control) to 26.9 +/- 2.2% (p < 0.001), with the intimal/medial ratio being decreased from 1.4 +/- 0.4 to 0.5 +/- 0.2 (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499414 TI - Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice. AB - MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia. PMID- 8499415 TI - [Pathology of the placenta. XIII. Pathological anatomy of the placenta and placental insufficiency]. AB - An account is given of morphological issues relating to placental insufficiency. Variable manifestations of placental insufficiency in foetuses and newborns are described in some detail. Reference is made to morphological clues useful in diagnosing causes of placental insufficiency. It proved to be particularly difficult to find quantitatively recordable parameters for such diagnosis, comparable to morphological indicators resulting from various placental measurements or from determination of exchange area and thickness measurement of placental basal membranes. Most of these quantitative methods, after all, would not even be applicable to routine examination. All the other diagnostic criteria of placental insufficiency are part of obstetrics (placental hormone production, measurement of uterus circulation and of intervillous space). In a more specialized section of this paper, reference is made to various pathologico anatomic patterns of placental disorders and their specific relevance to placental insufficiency. Circulatory disorders (maternal side), placental inflammation, impaired maturation and obliterative endarteriitis were the most common findings in this order. PMID- 8499416 TI - Gastric vascular ectasia in cirrhosis. AB - Eight cases of upper gastro-intestinal bleeding associated with liver cirrhosis are reported in this paper. Morphological studies revealed gastroduodenal ulceration with severe vascular changes in the mucosa and submucosa layer. Capillary dilatation was seen in the superficial region of the mucosa. Thick walled and tortuous vessels similar to angiodysplasia were noted in the submucosa. The latter vessels were surrounded by scar-like connective tissue considerably thickening the gastric submucous layer. It is assumed that scar-like thickening of the submucous layer surrounding the tele-angiectatic vessels causes microcirculatory disorders thus giving rise to bleeding ulcers. PMID- 8499417 TI - [Characterization of granulation and cicatrical tissue of chronic gastric ulcer. A light and electron microscopic investigation]. AB - Conventional histological and immunohistochemical methods as well as electron microscopy were used to investigate floor and margins of chronic ventricular ulcers of gastrectomy samples taken from 55 patients aged between 20 and 61 years. A distinction could be made between a superficial and a deep layer of granulation tissue as well as between instable and stable cicatricial tissue. Broadening of the superficial, immature layer of granulation tissue together with dystrophic alterations in the latter were shown to be signs of ulcer progression, whereas broadening and maturation of deeper layers of granulation tissue as well as thickening of the stable cicatricial zone were interpreted as morphological indicators to ulcer healing. The balance was instable among different zones of the ulcer wall and could possibly be shifted to either side, activation or healing of the ulcer. The direction actually taken by the process could be seen from the morphological pattern. PMID- 8499418 TI - [Immune tolerance in Masugi nephritis]. AB - Induction of immunotolerance was studied in the autologous phase of experimental rabbit glomerulonephritis. The glomerulonephritis was induced by intravenous injection of duck anti-rabbit glomerular basement membrane globulin into rabbits. One single intravenous injection of that nephrotoxis immunoglobulin (20 mg/kg body weight) into rabbits was followed by glomerulonephritis with glomerular hypercellularity and proteinuria. Another group of rabbits was pretreated on their first day of age, using 1.5 mg/animal of immunoglobulin from duck. Nephritis did not grow manifest when the animals received another injection (20 mg/kg body weight), after eight weeks. Passive (intracutaneous) Arthus reaction (triggered by duck immunoglobulin) was recordable with equal intensity from either group. PMID- 8499419 TI - Interaction of magnesium and calcium in meningioma. AB - Ca and Mg contents were determined in 57 meningiomas. Techniques included atomic absorption spectrometry, topochemical detection and electron probe analysis. Elastic fibres demonstrated positive reaction with reagents for detection of Mg. One third of the tumours showed Mg levels higher than Ca levels. The findings gave rise to discussion on the importance of competition and antagonism between Ca and Mg for the formation of calcified structures. As the collagen producing propensity of meningiomas is mediated by interaction with Mg, we speculate that, in addition to the amount of Mg required for basic cell functions, increased Mg levels are needed, especially in the fibromatous variant. PMID- 8499420 TI - [Disease-modifying factors in chronic polyarthritis. Correlations amongsystemic vasculitis, secondary amyloidosis, septic infections and occurrence of miliary epitheloid-cell granuloma. A review of autopsies]. AB - The following findings were obtained from autopsies performed on 169 deceased with chronic polyarthritis (CP): systemic vasculitis in 26 cases (15.4%), systemic secondary amyloidosis in 32 cases (18.9%), sepsis in 13 cases (7.7%) and miliary epithelioid-cell granulomatosis (probably tuberculosis) in six cases (3.6%). Vasculitis was combined with amyloidosis in five patients, with sepsis in two and with miliary epithelioid-cell granulomatosis in four. Critical random check, using the Mann-Whitney test, did not support significance of relationship between vasculitis and amyloidosis or fatal sepsis, whereas significant correlations were found to exist in CP cases between vasculitis and miliary epithelioid-cell granulomatosis (P < 0.005). The latter had no effect on the severity of vasculitis, but the incidence of the granulomatous type of vasculitis was higher with significance (P < 0.02). The conclusion is that biopsy evidence of granulomatous vasculitis in CP patients should be followed by systematic clinical search for miliary tuberculosis because of above-average incidence of that combination. PMID- 8499421 TI - Coronary atherosclerosis and chemical trace elements in the hair. A canonical correlation study of autopsy subjects, using an atherometric system and the X-ray fluorescence analysis. AB - An atherometric system (AS) was used to study coronary atherosclerotic lesions of a sample of 73 autopsy subjects. The content of nine chemical elements in the hair (K, Ca, Zn, Br, Sr, Pb, S, Cl, Cu) and the rates Zn/Cu and Ca/K were determined by energy dispersive X-ray fluorescence (EDXRF) analysis. Some canonical correlation analyses (CCA) were made of different combinations of chemical elements contents and of the following descriptive arterial variables of As: fatty streaks, fibrous plaques, severe (complicated plus calcified), plaques, and total atherosclerosis and the three weighted indices of AS, i.e. obstruction, stenosis and benignity. The arterial variables were obtained from the three major epicardial branches of the coronary arteries. Similar CCA analyses were performed to correlate chemical elements of the hair with some heart variables of AS, such as heart weight and estimated total volume of myocardium damaged by fibrosis and/or necrosis. The most remarkable results were as follows: Combinations of Pb, Ca/K, Zn/Cu and Fe, Ca/K, Zn/Cu were always strongly correlated with fatty streaks, fibrous plaques and severe plaques of the three coronary artery branches and the total coronary artery system, with the only exception of the left circumflex coronary artery when Fe was included. Similar results were recorded from obstruction, stenosis and benignity indices of AS. These two combinations of chemical elements were also correlated with the heart variables of AS. When the group of elements was integrated by Br, Ca/K, Zn/Cu, there were significant results with the heart variables, but not with the arterial variables of the AS. PMID- 8499422 TI - Collagen content in porcine myocardium and its impact on gross anatomical heart data, thyroid gland and adrenals. AB - 60 fattening pigs of the Leicoma breed were studied. The material was of high homogeneity (age 185 +/- 2 days, body weight 114 kg). The animals were raised and slaughtered under low-stress conditions. Collagen levels in both heart ventricles of each of the animals were morphometrically evaluated and were correlated with gross anatomical and histological data of the total body, heart, thyroid and adrenal cortices. The measured data are expected to be a representative basis for a pig breed with solid cardiovascular stability. The importance of the collagen content of the myocardium and factors of influence on it are discussed. PMID- 8499423 TI - [Osteochondrodysplasias. Prenatal diagnosis and pathological-anatomic findings]. AB - Prenatal sonographic investigations were applied for malformations to 7,194 foetuses, between October 1985 and April 1992, with 28 cases of osteochondrodysplasia (OCD) and one case of dysostosis being dissected. Included were 20 cases of lethal osteochondrodysplasia, among them two cases of lethal hypophosphatasia, five cases of thanatophoric dysplasia, one case each of Type II shortrib (polydactyly) syndrome (VERMA-NAUMOFF) and metatropic dysplasia, three cases of campomelic dysplasia and eight cases of Type II A imperfect osteogenesis. Also observed were eight cases of nonlethal OCD, among them three cases of diastrophic dysplasia and five of achondroplasia. Dysostosis was recorded from one case and was diagnosed as Type V acrocephalosyndactyly (Pfeiffer). Identification of a specific OCD proved to be difficult in the second or third trimenon. Hence, the form of OCD was prenatally diagnosed only in ten of all cases investigated. Tentative diagnosis was first established from the postmortem radiograph. Additional malformations and other abnormalities then were detected by complementary pathologico-anatomic processing of findings. The final diagnosis was derived from radiological, pathologico-anatomic and histological findings. Diagnosis of this constitutional osteopathy is quite difficult and calls for interdisciplinary cooperation between gynaecologists, neonatologists, paediatric surgeons, radiologists, geneticists and pathologists. More effective counselling of affected families is the major purpose of all the efforts involved. PMID- 8499424 TI - Nerve-like myoid differentiation in sclerosing adenosis of breast. A diagnostic pitfall. AB - A surgically excised lesion from the breast of a 33 year old woman showed apart from cystic disease sclerosing adenosis with distinct myoid differentiation. The myoid bundles were wrapped around original ductules producing a misleading picture which simulated tangentially cut nerves, infiltrated by tumour glands. Immunohistochemically, actin positivity and S-100 protein negativity confirmed the nature of the lesion as sclerosing adenosis. PMID- 8499425 TI - Cognitive distortion in depressed adolescents. AB - Cognitive theories of the etiology of depression in adulthood have received widespread acceptance. To date there is little evidence of the role of cognitive distortion in the etiology of depression among adolescents. This study was conducted to determine whether or not cognitive distortion differentiates depressed adolescents from non-depressed adolescents. The Dysfunctional Attitude Scale, a measure of cognitive distortion, was administered to three groups of adolescents: clinically depressed; non-depressed with non-psychotic psychiatric disorders; and a non-clinical group of adolescents without psychiatric disorders. A subset of the depressed patients was re-administered the scale after they had clinically recovered from the depressive episode. The depressed adolescents had significantly greater cognitive distortion than the non-depressed adolescents. Remission of the depressive disorder was associated with a significant reduction in cognitive distortion, although the level of cognitive distortion was still significantly higher than normal. PMID- 8499426 TI - Single photon emission computerized tomography in obsessive compulsive disorder: a preliminary study. AB - Patterns of cerebral perfusion in patients with obsessive compulsive disorder were evaluated using single photon emission computerized tomography. Eleven patients, who satisfied the DSM-III-R criteria and Research Diagnostic Criteria for the disorder, were evaluated using the distribution of 99m-Tc-HMPAO as a radiotracer. The Yale-Brown Obsessive Compulsive Scale was administered to each patient to assess the severity of their symptoms. The images obtained were evaluated qualitatively and semi-quantitatively by a physician in nuclear medicine who was blind to the patients' diagnoses. Eight of the 11 patients demonstrated asymmetric perfusion of the basal ganglia; the left side showed impaired perfusion in six patients. PMID- 8499427 TI - Reduction in suicidal ideation with SSRIs: a review of 459 depressed patients. AB - This paper is a review of 459 outpatients treated in double-blind clinical drug trials using similar protocols which compared the clinical responses to specific serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, mixed norepinephrine serotonin reuptake inhibitors, serotonin-2 antagonists and placebo. Although improvements in the total score on the Hamilton Rating Scale for Depression did not differ significantly among the groups, there were differences in the profile of response based on analysis of the items of the scale. The most striking difference was the significantly more rapid and effective improvement in depressed mood and the lessening of suicidal ideation among the patients treated with specific serotonin reuptake inhibitors. PMID- 8499428 TI - Neurobehavioral study of borderline personality disorder. AB - The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup. PMID- 8499430 TI - Toward maintenance of competence. PMID- 8499429 TI - A preliminary study of the relationship between central auditory processing disorder and attention deficit disorder. AB - Fifteen boys aged six to ten who met the criteria for attention deficit disorder (ADD) were compared with ten boys who did not have ADD in a double-blind, placebo controlled, single-crossover study of methylphenidate. To assess the degree of overlap between ADD and central auditory processing disorder (CAPD), all subjects were assessed on parent and teacher behavior rating scales, as well as a battery of CAPD tests at baseline and after three and six weeks of treatment. Twelve of the 15 subjects with ADD and none of the subjects without ADD met the criteria for CAPD. The subjects with ADD also responded to stimulant treatment on the measures of both ADD and CAPD. The overlap in the symptomatology of these disorders, the finding that the criteria for both disorders were met in 12 of 15 cases and the sensitivity of both ADD and CAPD measures to treatment with methylphenidate suggest that ADD and CAPD are closely related disorders. The implications of these results are three-fold. First, sustained attention is a critical feature of performance on CAPD tests and the current diagnostic criteria for CAPD make a clinical separation of the two disorders problematic. Second, stimulants appear to be a useful treatment for the symptoms of both ADD and CAPD. Third, CAPD tests may be a useful measure of ADD symptomatology and response to stimulants. PMID- 8499432 TI - Multiple magnesium ions in the ribonuclease P reaction mechanism. AB - The ribozyme ribonuclease (RNase) P cleaves precursor transcripts to produce the mature 5'-end of tRNAs. This hydrolysis reaction has a divalent cation requirement that is primarily catalytic, rather than structural; RNase P can be considered a metalloenzyme. Kinetic analysis shows that the RNase P catalytic mechanism has a cooperative dependence upon Mg2+ concentration. At least three Mg2+ ions are required for optimal activity, suggesting a multiple metal ion mechanism. The 2'-OH at the site of substrate cleavage may act as a ligand for a catalytically important Mg2+: deoxyribose substitution reduces the apparent number of Mg2+ bound from three to two and increases the apparent dissociation constant for Mg2+ from the micromolar to the millimolar range. In addition to these cation effects, the deoxyribose substitution reduces the rate of catalysis by 3400-fold; substitution with 2'-O-methyl at the cleavage site reduces the catalytic rate 10(6)-fold. If we presume no significant conformational effects of the substitutions, these results suggest that the 2'-OH serves as hydrogen-bond donor. The kinetic analysis of the catalytic mechanism is based upon the characterization of the pH dependence of the reaction. There is a hyperbolic (saturable) dependence on hydroxide concentration, with the half-maximal rate achieved at pH 8.0-8.5. The rate of the cleavage step is about 200 min-1 at pH 8.0, which is 500-fold faster than the steady-state parameter kcat. PMID- 8499431 TI - Can drugs cause depression? A review of the evidence. AB - Drug-induced depressive disorders are classified in the DSM-III-R as organic mood syndrome, depressed type. The ability of certain drugs to cause depression is of clinical relevance because organic mood syndrome is a component of the differential diagnosis of depressive symptoms. Consequently, psychiatric textbooks often provide different lists of drugs thought to be capable of causing depression. Strong evidence supporting the existence of causal associations is often lacking. There is no specific drug for which there is definitive evidence of a causal association with depressive symptoms or depressive disorders. Nevertheless, for a number of drugs, the evidence is suggestive, although not conclusively, of a causal association. Despite this, rational decisions about the continuation or discontinuation of drugs can often be made. In this paper, the literature is reviewed and guidelines are suggested for the management of patients with depressive symptoms which may be related to drugs. PMID- 8499433 TI - Structure and stability of an early folding intermediate of Escherichia coli trp aporepressor measured by far-UV stopped-flow circular dichroism and 8-anilino-1 naphthalene sulfonate binding. AB - The refolding kinetics of Escherichia coli trp aporepressor were monitored using stopped-flow far-ultraviolet circular dichroism and 8-anilino-1-naphthalene sulfonate fluorescence spectroscopy. Significant gains in secondary structure and the development of hydrophobic surface, respectively, were observed within the dead time of mixing (4-5 ms). These initial increases, or burst phase amplitudes, plotted as a function of final urea concentration, exhibited sigmoidal, coincident unfolding transition curves. The transition curves were fit to a two state model, and the resulting free energies of folding in the absence of denaturant were found to be similar (approximately 3.3 kcal/mol). Three subsequent slow refolding phases exhibited relaxation times and amplitudes similar to those previously observed for tryptophan fluorescence [Gittelman, M. S., & Matthews, C. R. (1990) Biochemistry 29, 7011-7021]. These results support the proposals that a stable, monomeric intermediate is rapidly formed during the folding of trp aporepressor and that this species contains a significant amount of secondary structure and hydrophobic surface. This early intermediate is then processed through folding and association reactions that result in the formation of the remaining secondary, tertiary, and quaternary structure. PMID- 8499434 TI - The Leptomonas collosoma spliced leader RNA can switch between two alternate structural forms. AB - We have used a combination of physical and molecular biological techniques to examine the structure of Leptomonas collosoma spliced leader RNA. We confirm the general features of the previously proposed structure for the 3' half of the RNA, in which a single-stranded region is flanked by two stem loops. However, we find that the 5' half of the RNA, which contains the splice site, has two competing secondary structures which differ only slightly in stability and which can interconvert on a fast (<1 s) time scale. In the favored conformation, a stable hairpin helix is augmented by conserved complementarity between the splice site and the 5' end of the SL RNA. This putative helix has anomalous nuclease sensitivity and thermal stability features, suggesting that it is probably coupled by unknown tertiary interactions to other nucleotides in the 5' half molecule. The structure offers intriguing parallels with RNA-RNA interactions in the mammalian splicing system. PMID- 8499435 TI - Reaction of modified and unmodified tRNA(Tyr) substrates with tyrosyl-tRNA synthetase (Bacillus stearothermophilus). AB - Three species of tRNA(Tyr) have been examined as substrates for the transfer reaction of the tyrosyl-tRNA synthetase (TyrRS) from Bacillus stearothermophilus: Escherichia coli tRNA(Tyr), B. stearothermophilus tRNA(Tyr) expressed in E. coli, and B. stearothermophilus tRNA(Tyr) that has been transcribed in vitro. The binding of the first two substrates to TyrRS may be readily monitored by stopped flow studies of tryptophan fluorescence to give the rate and equilibrium constants. The in vitro-transcribed tRNA(Tyr), which lacks the modified bases queuosine and 2-(methylthio)-N6-isopentenyladenosine in the anticodon loop, does not cause a significant change in tryptophan fluorescence upon binding. The three tRNA(Tyr) substrates exhibit very similar steady-state kinetics in the charging reaction. Pre-steady-state kinetics of the transfer reaction, monitored by stopped-flow measurements of the change in protein fluorescence on the addition of tRNA(Tyr) to the E.Tyr-AMP complex, show two exponential changes for the modified tRNA(Tyr) substrates. The first is that due to substrate binding. The second has an identical rate to the single change observed for the reaction with the in vitro-transcribed tRNA(Tyr) and to that monitored by quenched-flow measurements on the formation of Tyr-tRNA(Tyr). Hence, the transfer reaction can be observed by stopped-flow. The dissociation constants (KtRNA) of tRNA from the enzyme and rates of tyrosine transfer (k4) show that all three tRNA molecules are kinetically equivalent substrates for TyrRS. The value of k4 is also similar to that found for authentic tRNA(Tyr) from B. stearothermophilus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499436 TI - Use of binding energy in catalysis: optimization of rate in a multistep reaction. AB - The role of binding energy in optimizing the overall rate of catalysis by the tyrosyl-tRNA synthetase from Bacillus stearothermophilus has been investigated by measuring the rate constants for transfer of tyrosine from engineered mutants to tRNA. The residues chosen for mutation are those that were previously identified as binding tyrosyl adenylate and contributing to the rate constant for its formation. It was previously found that tighter binding of the tyrosyl adenylate was accompanied by an increase in the rate constant for its formation. A new linear free energy relationship is presented that links the two. We now find that the rate constant for transfer of Tyr from Tyr-AMP to tRNA decreases with increasing stability of the E.Tyr-AMP complex on mutation of Thr-51. Position 51 is the one that is found to be the most variable of the binding-site residues among the enzymes from different species. The tightness of binding of the intermediate is thus a compromise, since stabilizing the intermediate speeds up the first step but slows down the second. The rate constants for activation and transfer by wild-type enzymes are very similar, which is optimal for the rate of the overall reaction. Those for the mutants diverge so that the rate of overall catalysis is lower. PMID- 8499437 TI - Modularity of protein function: chimeric interleukin 1 beta s containing specific protease inhibitor loops retain function of both molecules. AB - Although it is widely recognized that many proteins contain discrete functional domains, it is less certain whether smaller, less obviously discrete, units of structure will retain their specific function when transplanted into a different context. The observation that the potent inflammatory cytokine human interleukin 1 beta has the same overall structure as soybean trypsin inhibitor (STI) (Kunitz) prompted us to replace a tight turn in the cytokine sequence with the large loop in soybean trypsin inhibitor that binds to the active site of trypsin. Wild-type interleukin 1 beta (IL-1 beta) is highly resistant to proteolysis, but the chimeric STI/IL is specifically cleaved by trypsin, apparently in the inserted loop. Other chimeric interleukins have also been constructed, by replacing the same tight turn with inhibitory loops from other protein protease inhibitors: turkey ovomucoid inhibitor (TOI), a chymotrypsin inhibitor, and alpha 1 antitrypsin (AT), an elastase inhibitor. Although these loops come from proteins not related structurally to interleukin 1, they confer specific protease sensitivity or inhibition on the chimeric cytokine. The cytokine properties of these chimeric interleukins have also been evaluated. The chimeras formed from human IL-1 beta and all inhibitory loops tested bind to the interleukin 1 receptor with reasonable affinity. The typical cellular effects of IL-1, however, are not observed with all the recombinant proteins, thus confirming that receptor binding and signal transduction can be uncoupled. When these results are taken together with the results of site-directed mutagenesis of IL-1, reported in this paper and elsewhere, they allow the receptor and intracellular transduction sites on the protein to be mapped in detail. PMID- 8499438 TI - Water-induced transitions in the K+ requirements for the activity of pyruvate kinase entrapped in reverse micelles. AB - The activity of pyruvate kinase was studied in reverse micelles formed with cetyltrimethylammonium bromide, n-octane, hexanol, and various amounts of water. In systems with 100% water, K+ is an essential activator of pyruvate kinase [Kachmar, J. F., & Boyer, P. D. (1953) J. Biol. Chem. 200, 669-683]; i.e., without and with K+, the activities observed were 0.07 and 300 mumol/(min.mg), respectively. In the micellar system with 3.6% water (v/v), pyruvate kinase exhibited an activity of about 45 mumol/(min.mg), in the absence of K+. The kcat was about 450 times larger than that in 100% water without K+. Km values for ADP and phosphoenolpyruvate differed, but not markedly from those in 100% water with or without K+. The kinetics of pyruvate kinase in reverse micelles were not affected by K+. The activity curve of pyruvate kinase in reverse micelles without K+ in a pH range of 6.0-8.5 was almost superimposable to that of the enzyme in 100% water with K+, and it differed drastically from that in 100% water without K+. The fluorescence emission spectra of pyruvate kinase in 100% water exhibited a blue shift of 3 nm upon the addition of ligands (Mg2+, phosphoenolpyruvate, and K+) that cause a transition of the enzyme to its active state. Without ligands, the entrapment of pyruvate kinase in reverse micelles with 3.0% water produced a blue shift of nearly 2 nm with respect to that of the enzyme in 100% water without ligands. As water was raised to 7.0% (v/v), the maximal emission shifted to longer wavelengths; these changes paralleled the appearance of the K(+) dependent activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499439 TI - Mass spectrometric identification and quantitation of arachidonate-containing phospholipids in pancreatic islets: prominence of plasmenylethanolamine molecular species. AB - D-Glucose induces insulin secretion from beta-cells of pancreatic islets by processes involving glycolytic metabolism and generation of ATP. Glucose also induces hydrolysis of beta-cell membrane phospholipids and accumulation of nonesterified arachidonate, which facilitates Ca2+ entry and the rise in beta cell Ca2+ concentration that is a critical signal in the induction of insulin secretion. Glucose-induced hydrolysis of arachidonate from beta-cell phospholipids is mediated in part by an ATP-stimulated, Ca(2+)-independent (ASCI) phospholipase A2 (PLA2), which, in vitro, prefers plasmalogen over diacylphospholipid substrates, but it is not known whether islets contain plasmalogens. We have identified and quantitated the major species of arachidonate-containing phospholipids in pancreatic islets by high-performance liquid chromatographic and mass spectrometric analyses. Arachidonate has been found to constitute 30% of the total islet glycerolipid fatty acyl mass. Ethanolamine phospholipids contain 30% of total islet arachidonate, and 44% of that amount resides in three plasmenylethanolamine molecular species with residues of palmitic, oleic, or stearic aldehydes in the sn-1 position. These endogenous islet plasmenylethanolamine species are hydrolyzed more rapidly than phosphatidylethanolamine species by islet ASCI-PLA2 in vitro and are also hydrolyzed in intact islets stimulated with secretagogues. ASCI-PLA2-catalyzed hydrolysis of islet plasmenylethanolamine species in vitro is inhibited by a selective haloenol lactone suicide substrate (HELSS) which is sterically similar to plasmalogens, and HELSS also inhibits all temporal phases of both eicosanoid release and insulin secretion from secretagogue-stimulated pancreatic islets. Islet beta-cell ASCI-PLA2-catalyzed hydrolysis of arachidonate from endogenous plasmenylethanolamine substrates may be an intermediary biochemical event in the induction of insulin secretion. PMID- 8499440 TI - Lipid bilayer partitioning and stability of camptothecin drugs. AB - The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to determine (1) the structural basis of drug binding to lipid bilayers, (2) the lipid bilayer stability of each drug's alpha-hydroxylactone moiety, a pharmacophore which is essential for antitumor activity, and (3) the site of drug binding in the bilayer. Equilibrium affinities of camptothecin and related congeners for small unilamellar vesicles composed of electroneutral dimyristoylphosphatidylcholine (DMPC) or negatively charged dimyristoylphosphatidylglycerol (DMPG) were determined using the method of fluorescence anisotropy titration. Experiments were conducted in phosphate buffered saline (PBS) at 37 degrees C and overall association constants (K values) were determined. Of the seven compounds studied, the new compound 9 chloro-10,11-methylenedioxy-(20S)-camptothecin (CMC) was found to display the highest membrane affinities (KDMPC = 400 M-1, KDMPG = 320 M-1), followed by 10,11 methylenedioxy-camptothecin and camptothecin, which exhibited KDMPC and KDMPG values of 100 M-1 or greater. Topotecan displayed markedly reduced binding to lipid bilayers (KDMPC = 10 M-1, KDMPG = 50 M-1). HPLC assays were subsequently employed to assess the relative stabilities of the lactone ring of membrane-bound drugs. Our results clearly indicate that lipid bilayer interactions stabilize the lactone moiety of camptothecin drugs. In comparison to half-lives in PBS (37 degrees C) of 17 and 19 min for camptothecin and CMC, respectively, DMPC- or DMPG bound drugs were found to be stable even for periods up to 72 h. Iodide quenching data indicate that membrane-bound camptothecin intercalates between the lipid acyl chains, in a protected environment well removed from the aqueous interface. In this manner lipid bilayer interactions stabilize the lactone ring structure of camptothecins and thereby conserve the biologically active form of each medication. PMID- 8499441 TI - Electric potentiation, cooperativity, and synergism of magainin peptides in protein-free liposomes. AB - Magainins, positively charged peptides present in the skin of Xenopus laevis, are known to permeabilize free-energy transducing membranes. Structural studies in otherwise protein-free model systems show alpha-helical magainins parallel to the membrane water interface. However, functional studies in biological membranes suggest that magainins operate as oligomeric complexes. Here we investigate whether magainins function as oligomers in protein-free liposomes also. We report that they do exhibit strong positive heterocooperativity. The magainins, magainin 2 and PGLa, act synergistically. Both activity and cooperativity are enhanced by net negative charge of the liposomal membranes. A transmembrane electric potential, negative inside, enhanced the activity of the peptides. We propose a model in which (i) binding to the surface of the membrane, mainly guided by electrostatic interactions, occurs and (ii) the bound form is in equilibrium with an n-meric complex of magainins spanning the membrane. PMID- 8499442 TI - Evidence that the hormone binding domain of steroid receptors confers hormonal control on chimeric proteins by determining their hormone-regulated binding to heat-shock protein 90. AB - Previously, it has been shown that the hormone binding domain of the glucocorticoid receptor acts as a transferable regulatory cassette that can confer hormonal control onto chimeric proteins [Picard, D., Salser, S. J., & Yamamoto, K. R. (1988) Cell 54, 1073-1080]. The hormone binding domain of the glucocorticoid receptor contains its site of interaction with the 90-kDa heat shock protein, hsp90 [Dalman, F. C., Scherrer, L. C., Taylor, L. P., Akil, H., & Pratt, W. B. (1991) J. Biol. Chem. 266, 3482-3490]. We have now transfected COS cells with cDNAs for fusion proteins containing beta-galactosidase and portions of the glucocorticoid receptor, and we demonstrate a correlation between hormone regulation of fusion protein localization and binding of the fusion proteins to hsp90. The hormone binding domain (residues 540-795) of the rat glucocorticoid receptor is sufficient for conferring hormone regulation onto a fusion protein and for intracellular binding of a fusion protein to hsp90. The hormone binding domain of the rat glucocorticoid or the human estrogen receptor is also sufficient to permit reticulocyte lysate-mediated refolding of a fusion protein into association with hsp90. Consistent with the results of fusion protein localization in intact cells, binding of a fusion protein to hsp90 blocks binding of antibody directed against the NL1 nuclear localization signal of the glucocorticoid receptor. These observations argue strongly that the hormone binding domain of the glucocorticoid receptor confers hormonal control of fusion proteins by conferring hormone-regulated binding to hsp90. PMID- 8499443 TI - Curvature, order, and dynamics of lipid hexagonal phases studied by deuterium NMR spectroscopy. AB - Solid-state deuterium (2H) NMR spectroscopy enables one to study both equilibrium and dynamical properties of membrane constituents at the molecular level and can yield significant insights regarding the organization of non-bilayer lipid aggregates. We have investigated a representative unsaturated phosphatidylethanolamine, viz., 1-perdeuteriopalmitoyl-2-linoleoyl-sn-glycero- 3 phosphoethanolamine, PLPE-d31, in the lamellar, or L alpha, phase and the reversed hexagonal, or HII, phase. Phosphorus-31 (31P) NMR studies of PLPE-d31 in the HII phase revealed that the chemical shift anisotropy of the phosphoethanolamine head groups, delta sigma, was scaled by the expected geometrical factor of -1/2 relative to the lamellar state. However, we found the occurrence of a further reduction in the 2H NMR quadrupolar splittings, delta vQ, of the 2H-labeled palmitoyl acyl chain segments. These observations point toward the role of interfacial curvature with regard to properties of reverse hexagonal phase lipids, and indicate that the pivotal position or neutral surface of approximately constant area may lie near the glycerol or polar head group region. Variations in the acyl chain packing due to curvature of the aqueous interface yield significant differences in the segmental order profiles as determined by 2H NMR spectroscopy. The latter reflect the local orientational order of the acyl chains and can be used together with simple statistical theories to extract positional or structural information. Average projected acyl chain lengths and mean interfacial or cross-sectional areas for PLPE-d31 in the different phases have been calculated. In addition, we describe a new means of estimating the radius of curvature of HII phase lipid aggregates utilizing 2H NMR spectroscopy, which is based on the difference between the lamellar and hexagonal phase order profiles. Here the radius of curvature, Rc, is defined as the distance from the center of the water core to the lipid/water interface, near the carbonyl segments of the acyl chains, giving Rc = 25.4-28.1 A for PLPE-d31 in the HII phase at 60 degrees C. This value is in good agreement with previous X-ray diffraction studies of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Alternatively, the data yield for the radius of the central water core that Rw = 17.8-20.5 A at 60 degrees C. The differences in geometry also lead to higher quadrupolar echo relaxation rates (R2e) for the lipid acyl segments closest to the aqueous interface in the HII versus the L alpha phase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8499444 TI - Relationship between annexin V tryptophan exposure, calcium, and phospholipid binding. AB - Annexin V is a Ca(2+)-dependent phospholipid-binding protein that may have one or more membrane-related functions, including inhibition of blood coagulation. The fluorescence of the single tryptophan of annexin V was used to monitor Ca2+ and/or phospholipid binding in terms of emission wavelength, emission intensity, and susceptibility to acrylamide quenching. In the absence of phospholipid, Ca2+ titration showed a strong red shift of the wavelength of maximal emission to approximately 345 nm, where a small increase in intensity occurred and was half maximal at approximately 3 mM Ca2+. The Stern-Volmer quenching constant due to acrylamide was only 5.2 M-1 for annexin V alone, indicating limited aqueous exposure of the tryptophan, but 36 M-1 for a Ca(2+)-bound form, indicating full exposure. Binding to both negatively charged and zwitterionic phospholipids was accompanied by a very large increase in fluorescence emission intensity, a red shift, and low exposure to acrylamide. Calculated concentrations of Ca2+ near the surface of negatively charged vesicles suggested that the exposure of tryptophan by Ca2+ binding to annexin V was sufficient for binding of the protein to all vesicles tested, including those composed of oleic acid and phosphatidylcholine (PC), but not to those composed of pure PC. When binding to PC was monitored, the phenomena associated with phospholipid binding were observed separately, at higher Ca2+ concentration, from the red shift and the high exposure to acrylamide due to Ca2+ binding alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499445 TI - Exchange, efflux, and substrate binding by cysteine mutants of the lactose permease of Escherichia coli. AB - In this study, wild-type lac permease and lac permease mutated at each of the eight cysteinyl residues in the molecule were solubilized from the membrane, purified, and reconstituted into proteoliposomes. Lactose equilibrium exchange and efflux activities of mutants with Ser in place of Cys117, Cys176, Cys234, Cys333, Cys353, or Cys355 are essentially the same as wild-type permease. In contrast, mutants in Cys148 and Cys154 exhibit diminished exchange and efflux activities. These mutants in Cys148 and Cys154, except for the C148S mutant, have previously been shown to slow down active transport as well [Van Iwaarden, P.R., Driessen, A. J. M., Menick, D. R., Kaback, H.R., & Konings, W. N. (1991) J. Biol. Chem. 266, 15688-15692]. C148S permease shows monophasic kinetics with a high apparent KM with respect to external lactose in the exchange reaction under nonequilibrium conditions, whereas wild-type permease exhibits biphasic kinetics with both a high and low KM component. Moreover, the absence of the low Km pathway in the C148S permease is correlated with the absence of a high-affinity binding site for p-nitrophenyl alpha-D-galactopyranoside (NPG). Interestingly, the affinity of the permease for NPG appears to increase with the hydrophobicity of the side chain at position 154 (Ser < Cys < Gly < Val). Finally, the presence of a high-affinity binding site for NPG in C154V is consistent with the biphasic exchange kinetics exhibited by this mutant. The results are discussed in the context of a model in which lac permease has two substrate binding sites, a catalytic site and a regulatory site. PMID- 8499446 TI - Acyl group transfer from the sn-1 position of phospholipids in the biosynthesis of n-dodecyl palmitate. AB - The wax ester n-dodecyl palmitate is shown to be synthesized by retinal pigment epithelial membranes. The biosynthesis of this ester is phospholipid dependent and occurs via the transfer of a palmitoyl group from the sn-1 position of lecithin to n-dodecanol. When retinal pigment epithelial membranes are used as the source of enzyme, the apparent Michaelis constant for n-dodecanol in this process is 65.8 microM, and the maximal velocity for n-dodecyl palmitate synthesis is 16.2 nmol/(h.mg of protein). The enzymatic activity is membrane associated and shows a maximum velocity between pH8 and pH9. This transesterification process appears to be similar to the lecithin retinol acyl transferase reaction and is a further example of acyl group transfer reactions from the sn-1 position of phospholipids. PMID- 8499447 TI - Flow-flash study of the reaction between cytochrome bo and oxygen. AB - The reaction between reduced cytochrome bo from Escherichia coli and oxygen has been studied using flash photolysis of the CO complex of the reduced protein after rapid mixing with oxygen. Absorbance changes were monitored in the alpha and Soret spectral regions. Two kinetic phases taking place at catalytically competent rates could be detected. The apparent rate constant obtained for both the first and second phase showed a hyperbolic dependence on the oxygen concentration. For the first phase, we obtained limiting first- and second-order rate constants at saturating and low oxygen concentrations of 4.5 x 10(4) s-1 and 1.6 x 10(8) M-1 s-1, respectively. The corresponding values for the second phase were 5 x 10(3) s-1 and 1.7 x 10(7) M-1 s-1. The first phase accounted for 30% of the total absorbance change in the Soret band (430 nm) and 15% of the total absorbance change in the alpha band (555 nm). These reactions are followed by a very slow phase with a lifetime of about 1 s. We have also studied the interaction between the fully oxidized enzyme and hydrogen peroxide, and we have found that peroxide binding induces an absorbance increase in the alpha band and a red shift of the Soret band. A consideration of the magnitude of the absorbance changes taking place during the first phase suggests that this reaction includes at least partial oxidation of the low-spin cytochrome b. PMID- 8499448 TI - Fourier transform infrared difference spectroscopy of the nicotinic acetylcholine receptor: evidence for specific protein structural changes upon desensitization. AB - We have previously reported a new method based on Fourier transform infrared spectroscopy for probing conformational changes that occur upon the binding of ligands to the nicotinic acetylcholine receptor (nAChR) [Baenziger, J. E., Miller, K. W. & Rothschild, K. J. (1992) Biophys. J. 61, 983-992; Baenziger, J. E., Miller, K. W., McCarthy, M. P. & Rothschild, K. J. (1992) Biophys. J. 62, 64 66]. Spectra are recorded using attenuated total reflection both in the presence and absence of agonists. The resulting nAChR "resting-to-desensitized" difference spectra reveal small highly reproducible infrared bands which can arise from vibrations of the agonist and structural changes in the nAChR membrane during the conversion of the receptor from the resting to desensitized state. In this work we have used a combination of different agonists and an antagonist along with isotopic labeling to assign bands in these spectra. nAChR membranes pretreated with the competitive antagonist alpha-bungarotoxin exhibit no bands above the noise level (approximately 10(-5) au) demonstrating that vibrations of the unbound agonist do not contribute to the normal difference spectrum. In contrast, bands in the resting-to-desensitized difference spectra are identified which can be assigned to the bound agonist, providing a means to probe its interaction and orientation in the binding site. Additional difference bands are due to secondary structural changes of the protein, perturbation of tyrosine(s), and changes in carboxyl groups possibly from Asp and/or Glu residues. Remarkably, some of these spectral changes are similar to those detected during the bleaching of the photoreceptor membrane protein rhodopsin. PMID- 8499449 TI - Reversible electrochemistry of fumarate reductase immobilized on an electrode surface. Direct voltammetric observations of redox centers and their participation in rapid catalytic electron transport. AB - Fumarate reductase (Escherichia coli) can be immobilized in an extremely electroactive state at an electrode, with retention of native catalytic properties. The membrane-extrinsic FrdAB component adsorbs to monolayer coverage at edge-oriented pyrolytic graphite and catalyzes reduction of fumarate or oxidation of succinate, depending upon the electrode potential. In the absence of substrates, reversible redox transformations of centers in the enzyme are observed by cyclic voltammetry. The major component of the voltammograms is a pair of narrow reduction and oxidation signals corresponding to a pH-sensitive couple with formal reduction potential E degree' = -48 mV vs SHE at pH 7.0 (25 degrees C). This is assigned to two-electron reduction and oxidation of the active-site FAD. A redox couple with E degree' = -311 mV at pH 7 is assigned to center 2 ([4Fe-4S]2+/1+). Voltammograms for fumarate reduction at 25 degrees C, measured with a rotating-disk electrode, show high catalytic activity without the low-potential switch-off that is observed for the related enzyme succinate dehydrogenase. The catalytic electrochemistry is interpreted in terms of a basic model incorporating mass transport of substrate, interfacial electron transfer, and intrinsic kinetic properties of the enzyme, each of these becoming a rate determining factor under certain conditions. Electrochemical reversibility is approached under conditions of low turnover rate, for example, as the supply of substrate to the active site is limited. In this situation, electrocatalytic half wave potentials, E1/2, are similar for oxidation of bulk succinate and reduction of bulk fumarate and coincide closely with the E degree' value assigned to the FAD. At 25 degrees C and pH 7, the apparent KM for fumarate reduction is 0.16 mM, and kcat is 840 s-1. Accordingly the second-order rate constant, kcat/KM, is 5.3 x 10(6) M-1 s-1. Under the same conditions, oxidation of succinate is much slower. As the supply of fumarate to the enzyme is raised to increase turnover, the electrochemical reaction eventually becomes limited by the rate of electron transfer from the electrode. Under these conditions a second catalytic wave becomes evident, the E1/2 value of which corresponds to the reduction potential of the redox couple suggested to be center 2. This small boost to the catalytic current indicates that the low-potential [4Fe-4S] cluster can function as a second center for relaying electrons to the FAD. PMID- 8499450 TI - Characterization of the quaternary structure and conformational properties of the human stem cell inhibitor protein LD78 in solution. AB - The human LD78 protein (sometimes referred to as human macrophage inflammatory protein-1 alpha) has been shown to protect multipotential hemopoietic stem cells from the effects of cytotoxic agents. Administration of the recombinant stem cell inhibitor molecule LD78 as an adjunct to chemotherapy has potential clinical benefit in reducing or preventing the neutropenia associated with this treatment. At physiological ionic strength, the 8-kDa LD78 molecule exists as soluble, heterogeneous, multimeric complexes of mass ranging from 100 to > 250 kDa. The hydrodynamic and structural properties of LD78 have been determined in various buffer solutions using analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy. The results demonstrate that defined, homogeneous monomer and tetramer forms of LD78 can be prepared which display distinct conformational properties. The combined use of hydrodynamic and spectroscopic analysis provides an insight into the pathway and molecular mechanics of LD78 self-association. PMID- 8499451 TI - Expression of glycosylated and nonglycosylated human transferrin in mammalian cells. Characterization of the recombinant proteins with comparison to three commercially available transferrins. AB - The coding sequence for human serum transferrin was assembled from restriction fragments derived from a full-length cDNA clone isolated from a human liver cDNA library. The assembled clone was inserted into the expression vector pNUT and stably transfected into transformed baby hamster kidney (BHK) cells, leading to secretion of up to 125 mg/L recombinant protein into the tissue culture medium. As judged by mobility on NaDodSO4-PAGE, immunoreactivity, spectral properties (indicative of correct folding and iron binding), and the ability to bind to receptors on a human cell line, initial studies showed that the recombinant transferrin, is identical to three commercial human serum transferrin samples. Electrospray mass spectrometry (ESMS), anion-exchange chromatography, and urea gel analysis showed that the recombinant protein has an extremely complex carbohydrate pattern with 16 separate masses ranging from 78,833 to 80,802 daltons. Mutation of the two asparagine carbohydrate linkage sites to aspartic acid residues led to the expression and secretion of up to 25 mg/L nonglycosylated transferrin. ESMS, anion-exchange chromatography, and urea gel analysis showed a single molecular species that was consistent with the expected theoretical mass of 75,143 daltons. In equilibrium binding experiments, the nonglycosylated mutant bound to HeLa S3 cells with the same avidity and to the same extent as the glycosylated protein and the three commercial samples. These studies demonstrate conclusively that carbohydrate has no role in this function. PMID- 8499452 TI - PCR cloning, sequence analysis and expression of the cybC genes encoding soluble cytochrome b-562 from Escherichia coli B strain OP7 and K strain NM522. AB - The cybC genes encoding cytochrome b-562 from B and K strains of Escherichia coli were shown to differ in size following their isolation by in vitro amplification using the polymerase chain reaction. Nucleotide sequencing of the genes and flanking regions revealed the discrepancy was due to a 26 bp deletion at the 5' end of the K strain sequence that included the initiation codon. Expression studies confirmed that the K strain gene was untranslated. These data indicate that the cybC gene product is non-essential in E. coli. PMID- 8499453 TI - Inhibition of mitochondrial translation by calmodulin antagonist N-(6-aminohexyl) 5-chloro-1-naphthalenesulfonamide. AB - The possible role of calmodulin in mitochondrial functions was investigated in Ehrlich ascites tumor cell and mouse liver mitochondria employing sulfonamide compounds as calmodulin indicators. N-[6-Aminohexyl)-5-chloro-1 naphthalenesulfonamide (W7), the most potent of the sulfonamide compounds, inhibited mitochondrial protein synthesis and oxidative phosphorylation. The inhibitors had no significant effect on mitochondrial cytochrome c oxidase, oligomycin-sensitive ATPase and NADH dehydrogenase activities. Depletion of endogenous ATP pool seemed to be the main mechanism of inhibition of mitochondrial translation by sulfonamides. The results also show that mitochondria from hepatic tissues are relatively less sensitive to sulfonamide drugs as compared to the Ehrlich ascites tumor cell mitochondria. Results of Ca2+ autoradiography revealed 2-3-fold higher levels of calmodulin-like Ca2+ binding protein in extracts from Ehrlich ascites tumor cell mitoplasts as compared to mitoplasts from mouse liver. These results suggest cell and tissue specific variations in Ca(2+)-dependent processes in the mitochondrial compartment. PMID- 8499454 TI - Synergistic activation of the human red cell calcium ATPase by magnesium and vanadate. AB - The Ca(2+)-ATPase activity of human red cells was studied on calmodulin-free membrane fragments after previous incubation with Mg2+ and vanadate. In the presence of EGTA (5 mM), the activity was slightly affected by either ion alone. However, when added together, both Ca2+ affinity and Vmax were increased up to levels found with calmodulin (0.3 microM). This synergistic activation was not abolished by proteinase inhibitors (iodoacetamide, 10 mM; leupeptin, 200 microM; pepstatin A, 100 microM; phenylmethanesulfonyl fluoride, 100 microM), neomycin (200 microM), washing with EDTA (5 mM) or by both incubating and washing with delipidized serum albumin (1 mg/ml). During preincubation under optimal Mg2+ and vanadate conditions, the replacement of K+ by Na+ or Li+ was without effect. Co2+ or Zn2+ (10 mM) could not substitute for Mg2+, whereas Mn2+ almost replaced it at equimolar amounts. By contrast, addition of ATPMg (2 mM) decreased the activation by about one-half. Like calmodulin, pretreatment with Mg2+ plus vanadate also increased the affinity for ATP and elicited appearance of a second (low) affinity site (apparent Km = 120 microM). The fluorescence depolarization of 1,6-diphenyl- and 1-(4-trimethylammonium phenyl)-6-phenyl 1,3,5-hexatriene incorporated into membrane fragments was not affected after preincubating with Mg2+, vanadate or Mg2+ plus vanadate. The results show that Mg2+ and vanadate are acting neither via proteolysis or fatty acid production nor by facilitating phospholipid metabolism or altering membrane fluidity. They may be enhancing the Ca(2+)-ATPase activity by stabilizing the E1 conformer or promoting an enzyme conformation which facilitates the E2-E1 transition. PMID- 8499455 TI - ATP-driven potassium transport in right-side-out membrane vesicles via the Kdp system of Escherichia coli. AB - The ATP-generating system described by Hugenholtz, J., Hong, J.-S. and Kaback, H.R. ((1981) Proc. Natl. Acad. Sci. USA 78, 3446-3449) has been used to synthesize ATP up to 1.8 mM in right-side-out membrane vesicles from Escherichia coli. This ATP level was sufficient to drive uptake of potassium ions via the Kdp ATPase. In the kdp wild type strain about 110 nmoles K+/mg membrane protein were accumulated. This process was still partially sensitive to the well-known inhibitors of P-type ATPases, orthovanadate and bafilomycin B1. PMID- 8499456 TI - The acute effects of the creatine analogue, beta-guanidinopropionic acid, on cardiac energy metabolism and function. AB - 1. Perfusion of isolated rat hearts with 150 mM beta GPA led to the linear accumulation of intracellular P beta GPA (approx. 150 nmol/min per g (dry wt.)) after an initial lag period of 20 min. 2. This accumulation of intracellular P beta GPA was accompanied by a decrease in PCr (30%) and an increase in total phosphagen content (20%). These results show that PCr was not equally replaced by P beta GPA, but was degraded at the expense of beta GPA phosphorylation to produce a net increase in cardiac phosphagen content. Correspondingly, total phosphate (the sum of PCr, P beta GPA, Pi and ATP) was increased, indicating that there was no cellular necrosis and that the sarcolemma remained intact throughout the perfusion. 3. An increase in Pi and decrease in ATP also occurred concomitantly with P beta GPA accumulation, indicating that ATP synthesis was not keeping up with demand. This may be due to the gradual replacement of PCr by the less efficient phosphagen, P beta GPA, resulting in inadequate transduction of energy and hence an imbalance between energy demand and supply. However, the increased hyperosmolarity of the perfusate may be partly responsible for these effects on cardiac energy metabolism, as perfusion with 150 mM mannitol produced a similar decrease in ATP, but a smaller rise in Pi. 4. Perfusion with either 150 mM beta GPA or mannitol led to a significant intracellular alkalosis (max. pHi 7.3), which was reversed on returning to normal perfusate. In addition, both hyperosmolar perfusions led to a significant reduction in cardiac frequency (40 and 15%, respectively). However, only beta GPA caused significant negative inotropism. The time-courses for the changes in cardiac frequency and pHi did parallel the increase in P beta GPA. This suggests that both hyperosmolarity and the production of P beta GPA during beta GPA perfusions determine the degree of negative chronotropism, but that hyperosmolarity alone causes alkalosis and beta GPA phosphorylation, a decrease in developed tension. 5. When hearts, acutely loaded with P beta GPA were perfused with control medium, the levels of ATP, PCr and P beta GPA stabilised to produce a new steady state. There was no decrease in P beta GPA concentration during this procedure, implying that beta GPA efflux was negligible. PMID- 8499457 TI - The diffusional transport of water and small solutes in isolated endothelial cells and erythrocytes. AB - The diffusional permeability coefficients, PD, for tritiated water (3HHO) 14C antipyrine (AP) and 14C-iodoantipyrine (IAP) in isolated calf pulmonary artery endothelial cells and dog erythrocytes are measured with the linear diffusion technique at 11.5, 15, 20 and 37 degrees C. The PD values for both cell populations follow the sequence 3HHO > IAP > AP at each of the temperatures. PD for water is higher in the erythrocyte compared to the endothelial cells. The differences in PD for AP and IAP in the erythrocytes and endothelial cells are not dramatic and are similar to the differences seen in comparing permeation of the same solute through bilayers of different composition. A comparison of the values of PD calculated for the endothelial cells with those for isolated capillaries and the structured endothelium in whole lungs validates the use of the isolated cells as models for the endothelial cells in situ. Incubation of the endothelial cells with cis-vaccenic acid or cholesterol produces a reduction in PD for water and antipyrine. These data are analyzed in terms of Stokesian and non-Stokesian diffusion. The interpretation which best accommodates the data is that the phospholipid area of the membrane, rather than the hydrocarbon core, provides the greatest resistance to permeation for these solutes. PMID- 8499458 TI - Uptake of phosphate by rat hepatocytes in primary culture: a sodium-dependent system that is stimulated by insulin. AB - Primary cultures of rat hepatocytes take up phosphate by a saturable Na(+) dependent process. Thus the plasma membrane possesses an N(+)-Pi cotransporter of the type described for many cell types, e.g., kidney proximal tubular cells and enterocytes. Coupling to Na+ overcomes the barrier to anion entry represented by the membrane potential. At 0.12 mM Pi, the effect of Na+ is cooperative with a Hill coefficient of 1.7 suggesting two sodium sites per molecule of carrier. At 37 degrees C, the Km (for Pi) and Vmax for the sodium-dependent fraction of Pi uptake are approx. 1 mM and 0.35 nmol Pi/min per mg cell protein, respectively. Insulin stimulates Vmax four-fold with no significant effect on Km. Pi uptake in the absence of sodium is not affected by insulin. The stimulation by insulin could be of metabolic significance. Glucose phosphorylation at the expense of ATP is raised in liver following insulin stimulation, and thus, initially there may be an increased demand for Pi for oxidative phosphorylation until new steady state conditions of hexose phosphate concentrations and of ATP turnover become established. PMID- 8499459 TI - The reduction of the inhibitory effect of aluminum on Na+ efflux in barnacle muscles fibers by preinjecting phosphate. AB - The object of the present study was to test the hypothesis that the pre enrichment of single muscle fibers from the barnacle Balanus nubilus with inorganic phosphate may protect the basal Na efflux from the inhibitory effect of Al injection. This approach was adopted in the light of evidence that the preinjection of ATP fails to stop the Na efflux in unpoisoned fibers from falling following the injection of Al. The results of the experiments are as follows: (i) Preinjection of K2HPO4 into unpoisoned fibers reduces the magnitude of the inhibitory effect on the basal Na efflux of injected Al in a dose-dependent manner but fails to completely stop it from occurring. (ii) Injection of K2HPO4 following Al into unpoisoned fibers fails to arrest or reverse the inhibitory effect of injected Al. (iii) Injection of K2HPO4 in a concentration as high as 0.5 M is without effect on the course of the basal Na efflux. (iv) Injection of K2HPO4 into ouabain-poisoned fibers fails to stop Al from stimulating the ouabain insensitive Na efflux. Injection of K2HPO4 following peak stimulation by injecting Al is also without effect. (v) Injection of K2HPO4 in a concentration as high as 0.5 M is without effect on the course of the ouabain-insensitive Na efflux. Collectively, the results obtained with unpoisoned 'hypersensitive' fibers are consistent with the view that a significant fraction of the injected inorganic phosphate binds Al3+, and hence protects the basal Na efflux from the untoward action of Al3+. PMID- 8499460 TI - Induction of a 23 kDa stress protein by oxidative and sulfhydryl-reactive agents in mouse peritoneal macrophages. AB - The synthesis of 23 kDa protein was enhanced when mouse peritoneal macrophages were exposed to oxidative agents such as hydrogen peroxide and menadione, or to sulfhydryl-reactive agents such as diethylmaleate, cadmium chloride and sodium arsenite. After 11 h exposure to these agents the 23 kDa protein was one of the actively synthesized proteins in the macrophages. Under similar conditions the 34 kDa protein previously identified as heme oxygenase, was induced and its synthesis preceded that of the 23 kDa protein. Neither the 23 kDa or the 34 kDa protein was induced by hyperthermia. Conversely, the various oxidative and sulfhydryl-reactive agents employed here did not induce the major heat shock proteins in the macrophages. When the macrophages were activated by bacterial lipopolysaccharide or other stimulants, many proteins are known to be induced, however, the 23 kDa and 34 kDa proteins were not induced. The 34 kDa protein, i.e., heme oxygenase, has been found to be stress-induced in various types of cell, but not the 23 kDa protein. This suggests that the 23 kDa protein is a stress protein predominantly expressed in macrophages. PMID- 8499461 TI - Isolation and influenza virus receptor activity of glycophorins B, C and D from human erythrocyte membranes. AB - (1) Glycophorins (GPs) AM, AN, B, C and D were each isolated into a high state of purity from human erythrocyte membranes by a combination of lithium diiodosalicylate (LIS)-phenol extraction, gel-filtration with Bio-Gel A1.5m and HPLC with LiChrospher 1000 TMAE. (2) GPs-B, -C and -D reacted with influenza A and B viruses as well as GPs-AM and -AN and the order of reactivities against two viruses of the glycophorins was as follows: GP-B > GP-C > GP-AM = GP-AN >> GP-D for the former virus and GP-C > GP-B > GP-AM = GP-AN >> GP-D for the latter virus. PMID- 8499462 TI - Fluorescence anisotropy studies on the interaction of the short chain n-alkanols with stratum corneum lipid liposomes (SCLL) and distearoylphosphatidylcholine (DSPC)/distearoylphosphatidic acid (DSPA) liposomes. AB - Previously, the action of the short chain n-alkanols (from C1 to C5) and isopropanol as possible enhancers on the transport of lipophilic and polar/ionic permeants across hairless mouse skin was investigated. In the present study, the steady-state fluorescence anisotropy was measured as a means of estimating the changes in fluidity caused by the n-alkanols at different depths in the stratum corneum lipid liposomes (SCLL). Some selected experiments with the distearoylphosphatidylcholine (DSPC)/distearoylphosphatidic acid (DSPA) liposomes were performed for relative comparisons. The effects of the n-alkanols on polarity sensitive parameters such as fluorescence lifetimes, fluorescence quantum yield ratios, and emission maxima were studied in the SCLL. The polarity of the bilayer decreased as the fluorescent probe was placed closer to the bilayer center and the n-alkanols did not alter this gradient. Assessment of the depth-dependent effects of the n-alkanols using SCLL showed that most of the significant changes in fluidity induced by the n-alkanols were observed at intermediate depths (C2-C9) and there was little or no increase in fluidity in the deep hydrophobic region close to the bilayer center. These results suggest that the short chain n-alkanols work as effective 'fluidizing' agents at the intermediate depths (C2-C9) in the bilayer. PMID- 8499463 TI - The distribution of intracellular calcium chelator (fura-2) in a population of intact human red cells. AB - Using quantitative fluorescence microscopy of red cells loaded non-disruptively with 1-2.5 mmol/l cells of fura-2, we examined the distribution of the incorporated free chelator among and within individual cells. Cytoplasmic hemoglobin quenched the effective fluorescence yield of fura-2 by a factor of about 100. All red cells were found to fluoresce upon excitation at 380 nm, and the fluorescence intensities they emitted at 510 nm were approximately +/- 20% about the mean intensity, indicating a fairly uniform distribution of incorporated chelator among the cells. Red cells loaded with these high levels of fura-2 retained their biconcave shape, and a comparison between their transmission images at 415 nm and their fura-2 fluorescence images suggests that the concentration of fura-2 was also uniform throughout the cytosol. These results validate assumptions made in earlier experiments with non-fluorescent incorporated Ca2+ chelators, and demonstrate the feasibility of fura-2 and Ca2+ imaging of intact red cells, despite considerable quenching of probe fluorescence by hemoglobin. PMID- 8499464 TI - In-vitro stability and cytostatic activity of liposomal formulations of 5-fluoro 2'-deoxyuridine and its diacylated derivatives. AB - The water-soluble antineoplastic agent 5-fluoro-2'-deoxyuridine (FUdR) was encapsulated in the water phase of liposomes of different lipid compositions. The retention of this drug upon storage and during contact with plasma was assessed. It was found that, upon refrigeration, diffusion of FUdR across the liposome bilayer was considerably faster when the drug was encapsulated in fluid-type liposomes (egg PC/PS/CHOL) than in solid-type liposomes (DSPC/DPPG/CHOL). With either composition, leakage of the drug from the liposomes was accelerated upon contact with plasma. To achieve improved liposomal retention of the drug, FUdR was converted to a lipophilic prodrug by esterifying the free hydroxyl groups in the deoxyribose moiety with fatty acids of different chain lengths. Thus FUdR dipalmitate (C-16) and FUdR-dioctanoate (C-8) were synthesized and incorporated in liposomes. The dipalmitoyl derivative could be incorporated upto 13 mol% in solid-type liposomes but to only 2 mol% in fluid-type liposomes. Freeze-fracture electron microscopy revealed no major differences between control liposomes and those containing the prodrug. FUdR-dipalmitate was found to be firmly associated with the liposomal bilayer in both liposome-types: no exchange of the pro-drug with blood constituents or hydrolysis by serum esterases could be registered when the liposomes were incubated with serum. On the other hand, liposome-incorporated FUdR-dioctanoate was found to be readily extracted from the liposomes by serum components (predominantly albumin) and was found to be degraded rapidly by serum esterase activity. The antitumor activity of FUdR-prodrugs was determined using C26 colon adenocarcinoma cells. This cell line was found to be highly sensitive to FUdR. Liposomal FUdR-dioctanoate inhibited cell growth in the same concentration range as unesterified FUdR. FUdR-dipalmitate, however, was more than two orders of magnitude less potent in inhibiting cell proliferation. Its antiproliferative activity was dependent on the liposome-type used: when incorporated in fluid-type liposomes, antiproliferative activity of FUdR dipalmitate was several-fold higher than in solid-type liposomes. The difference in antitumor activity between FUdR-dipalmitate and FUdR-dioctanoate and between FUdR-dipalmitate in the fluid- and solid-type liposomes could be explained by differences in the rate of hydrolysis of the prodrugs to FUdR by esterase activity in the tumor cells or in the growth medium. PMID- 8499465 TI - Two yeast peroxisomal proteins crossreact with an antiserum against human sterol carrier protein 2 (SCP-2). AB - An antibody raised against human sterol carrier protein 2 (SCP-2) crossreacts with two yeast peroxisomal proteins. These proteins have apparent molecular weights of 35 and 58 kDa. Subfractionation of peroxisomes revealed that the 58 kDa species is a soluble matrix protein, whereas the 35 kDa protein is membrane bound. Treatment of isolated peroxisomal membranes with 0.25 M KCl released the 35 kDa crossreactive protein into the soluble supernatant. However, lipid transfer activity could be attributed neither to the 35 kDa nor to the 58 kDa protein. PMID- 8499466 TI - Structural domain mapping and phosphorylation of human erythrocyte pallidin (band 4.2). AB - Pallidin (band 4.2) is a major protein of the human erythrocyte membrane, and plays an important but as yet undefined role in maintaining the normal shape and lifespan of the erythrocyte. The pallidin protein has been purified by a new procedure which yields a protein which is > 97% pure as judged by gel electrophoresis, while pallidin purified by our original procedure is only approx. 85% pure. The new form of the protein is unstable in physiological salt solutions. However, taking advantage of its high purity, we have used the new form of the protein to produce a structural domain map of its principal tryptic fragments. We also show that pallidin can be phosphorylated by a red-cell membrane kinase which partially co-purifies with it, and has properties similar to the catalytic subunit of cAMP-dependent kinase. Both cAMP-dependent kinase and the red-cell kinase phosphorylate the same tryptic domains on the pallidin protein. Our results show that endogenous pallidin on the red-cell membrane is a poor substrate for the kinase, possibly because it is fully phosphorylated, or inaccessible to the kinase. PMID- 8499467 TI - Divalent cations, phospholipid asymmetry and osmotic swelling in electrically induced lysis, cell fusion and giant cell formation with human erythrocytes. AB - We have previously reported that acidic phospholipids are exposed at the surface of human erythrocytes when the cells are subjected to electrical breakdown. It has now been shown that the prothrombinase assay, which was used previously for the determination of acidic phospholipids, is specific for phosphatidylserine under the conditions of our experiments. In the light of this finding, we have investigated and characterised factors that govern cell lysis, cell fusion, and the formation of giant cells induced by electrical breakdown with human erythrocytes in media of low ionic strength. Divalent cations (1.1 mM) protected the cells against haemolysis, in the order Mn2+ > Ca2+ > Ba2+ > Mg2+ >> Zn2+, whereas about 99% of the cells lysed immediately on breakdown in the presence of Na+ or K+ (2.1 mM), or Al3+ (0.95 mM). The lengths of pearl chains of fused erythrocytes formed was similarly greatest with Mn2+ and decreased progressively with Ba2+, Zn2+, Ca2+ and Mg2+. No cell fusion occurred with Na+, K+, or Al3+. It is suggested that interactions with phosphatidylserine, which is exposed at the cell surface by electrical breakdown, may enable Mn2+, Ba2+ and Ca2+ ions to inhibit cell lysis (via membrane resealing) and facilitate cell fusion. Following electrically-induced cell fusion, erythrocytes round-up into giant cells. It has previously been proposed that Ca2+ ions accelerate the rounding-up process. However, data are presented which show that, as with erythrocytes treated with Sendai virus, the formation of rounded, giant cells following cell fusion depends on the osmotic swelling properties of permeabilised erythrocytes. Osmotic swelling may also have induced any hemi-fused cells present to fuse completely. Zn2+ ions anomalously enabled erythrocytes to round-up very rapidly into giant cells following electrical breakdown. This phenomenon may result from an interaction of Zn2+ ions with cysteine groups in membrane proteins, which decreases the immediate loss of ions that occurs when erythrocytes are subjected to electrical breakdown in low-ionic-strength media. PMID- 8499468 TI - Polycation-induced enhancement of epithelial paracellular permeability is independent of tight junctional characteristics. AB - The nature of polycation-induced change in transepithelial permeability was investigated in strains I (tight) and II (leaky) MDCK epithelial monolayers. Apical exposure to poly(L-lysine) (PLL, mol. wt. (MW) approximately 20,000) induced a dose-dependent increase in transepithelial conductance (GT) in both strains which correlated with increasing transepithelial flux of extracellular markers (thiourea/inulin) indicating that PLL enhanced paracellular permeability in these epithelia. Coincident with the increase in GT, PLL also induced an inward short circuit current (Isc) which was associated with the early phase of the increase in GT and may be responsible for part of it. Morphological studies showed that immunofluorescent staining of the tight junction protein, ZO-1, was abolished following PLL exposure. In addition, F-actin staining in monolayers challenged with PLL demonstrated breaks in the zonulae occludentes at the apical surface. PLL had similar effects on monolayers of T84 and HCT-8 human intestinal cells indicating that polycation action may be general for a range of epithelial types. We conclude that epithelial exposure to polycations results in opening of the paracellular route by mechanisms which are independent of tight junction characteristics. PMID- 8499469 TI - Identification of a hepatic plasma membrane glutathione S-transferase activated by N-ethylmaleimide. AB - Rat liver plasma membranes exhibit membrane-bound glutathione S-transferase activity. The specific activity in isolated canalicular membranes was 83 +/- 8 mU/mg protein and 50 +/- 3 mU/mg protein in the sinusoidal membranes. Whereas microsomal and outer mitochondrial glutathione S-transferases were stimulated seven and four-fold with N-ethylmaleimide, respectively, the plasma membrane activity was activated two-fold. Western blot analysis, using an antibody against the microsomal glutathione S-transferase, shows the presence of a 17 kDa protein in canalicular and sinusoidal membrane fractions. The antibody reaction was about three-fold higher in the canalicular compared to the sinusoidal membrane fraction. These data support the conclusion that the plasma membrane glutathione S-transferase is closely related to the microsomal and outer mitochondrial membrane enzyme. PMID- 8499470 TI - Monoclonal antibodies against luminal membranes of renal proximal tubules which are kidney-specific. AB - After immunization with porcine brush-border membrane proteins, 11 monoclonal antibodies were generated which react with proximal tubules. Their antigenic polypeptides were characterized with respect to apparent molecular weight, histochemical localization in porcine and human kidney, and tissue distribution in pig. In porcine kidney, six antibodies bind selectively to the proximal tubule whereas the others also react with other nephron segments. With the exception of one antibody which reacts with the luminal and the basolateral membrane of the porcine proximal tubule, the other antibodies specific for the proximal tubule only stain the brush-border membrane. Four of them react along the entire length of the porcine proximal tubule, whereas one (R1A2) binds to the S3-segment in pig and to the entire length of the proximal tubule in man. This indicates that segment-specific expression may be species-dependent. Testing the antibodies in 21 different extrarenal tissues it was found that three of the antibodies, specific for the brush-border membrane in renal proximal tubules, only react in kidney. Two of these are specific for pig kidney whereas one also reacts with human kidney. This antibody (N4A4) is directed against a polypeptide with an apparent molecular weight of 400,000. Electron microscopic immunohistochemistry showed that N4A4 binds to the intervillus region of the brush-border membrane and to subapical vesicles. PMID- 8499471 TI - DIDS inhibition of deformation-induced cation flux in human erythrocytes. AB - The permeability of human erythrocytes to sodium, potassium and calcium increases when the cells are deformed by shear. We now report that the anion-exchange inhibitor DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) inhibited 55 60% of the deformation-induced flux with an apparent K1/2 of 1 microM. Covalently bound DIDS was also effective. In cells partially derivatized at 0 degrees C (pH 7.4), anion exchange and the deformation flux were inhibited in parallel, implying that lysine a is the site of inhibition for both fluxes. Ektacytometry showed that DIDS does not inhibit by lowering the cell's ability to deform. Crosslinking of lysines in Band 3 was not required for inhibition of the stress flux, as demonstrated by electrophoretic analysis of chymotrypsin-cleaved Band 3 after DIDS treatment. Chymotrypsin cleavage itself did not affect the cation flux rates. DNDS, an anion exchange inhibitor that binds to the chloride site on Band 3 but is unable to derivatize lysine a, is an ineffective inhibitor of the deformation flux. Other high-affinity inhibitors of anion exchange were also relatively ineffective against the deformation flux, and anion exchange itself was unchanged by shear. These results suggest that 55-60% of the deformation induced cation movement traverses a route that includes Band 3, but is distinct from the pathway utilized by anion exchange. Chloride-dependent cation pathways do not participate in the stress induced cation flux, since complete exchange of intracellular chloride for sulfate had no effect on the rates. Deformation of erythrocytes by laminar shear appears to increase the non-specific cation permeability. PMID- 8499472 TI - Polymer-derivatized technetium 99mTc-labeled liposomal blood pool agents for nuclear medicine applications. AB - By using the lipophilic chelator, dipalmitoylphosphatidylethanolamine diethylenetriaminetetraacetic acid (DPPE-DTTA), lipid vesicles may be prepared labeled on their surface with technetium 99m. When technetium-labeled vesicles were injected intravenously into rabbits, the half-life for clearance of the label from the circulation was less than 30 min. By further incorporating a synthetic phosphatidylethanolamine-monomethoxypoly(ethylene glycol) 5000 conjugate (PE-MPEG) the circulation half-life of the radiolabel was increased, liver uptake decreased and exchange of technetium from the vesicle surface suppressed, depending upon both the DPPE-DTTA and PE-MPEG content. For vesicles containing 20 mol% DPPE-DTTA, incorporation of PE-MPEG had no effect upon the circulation half-life of the radiolabel, however, for vesicles containing 2 mol% DPPE-DTTA, incorporation of more than 4 mol% PE-MPEG increased the circulation half-life of the label to more than 12 h. Less than 2 mol% PE-MPEG or 8 mol% ganglioside GM1 were, however, ineffective at increasing the circulation half life of surface-bound technetium. It was shown that unilamellar lipid vesicles with DPPE-DTTA can be lyophilized in the presence of external sucrose, subsequently rehydrated with no change in vesicle size and labeled with technetium. It is suggested that polymer-derivatized, technetium-labeled vesicles may prove a useful substitute for technetium-labeled red blood cells as a vascular marker in various nuclear medicine procedures and that lyophilization/rehydration provides a possible route to realization of such vesicles in a pharmaceutically useful form. PMID- 8499473 TI - Membrane changes in lipopolysaccharide-stimulated murine B lymphocytes associated with cell activation. AB - The lateral diffusion of the fluorescent lipid analog 3,3' dioctadecylindocarbocyanine iodide (DiI) was measured in the membranes of murine B lymphocytes treated with the B cell mitogen lipopolysaccharide (LPS). The mobility of DiI, as measured by fluorescence photobleaching recovery (FPR) techniques, was temperature-dependent with a value of 6.1.10(-9) cm2 s-1 at 37 degrees C. Untreated cells exhibited this diffusion coefficient over 72 h in culture. In contrast, DiI mobility decreased to 2.0.10(-9) cm2 s-1 at 37 degrees C in membranes of LPS-stimulated lymphocytes 24 h following LPS exposure. Interestingly, this decreased lipid lateral diffusion was not accompanied by any change in surface immunoglobulin lateral diffusion which remained essentially unchanged at 3.6-4.3.10(-11) cm2 s-1 over 72 h. To determine whether LPS effects on lipid lateral diffusion were due to insertion of LPS into the cell plasma membrane, we examined TRITC-LPS diffusion in B lymphocytes from LPS-responsive Balb/c and C3Heb/FeJ mice and from hypo-responsive C3H/HeJ mice. DiI and TRITC LPS mobility decreased more than 50% in LPS-stimulated Balb/c and C3Heb/FeJ cells by 72 h. On C3H/HeJ lymphocytes, there was no change in DiI or TRITC-LPS lateral diffusion throughout the incubation period. These data indicate that B lymphocyte membrane composition is altered in LPS-activated lymphoblasts and that the decreased lateral diffusion of lipid probes does not result from membrane perturbation by LPS insertion into the lipid bilayer. Further, similarities between TRITC-LPS and DiI lateral diffusion suggest that most LPS molecules interact non-specifically with B cell membranes, presumably by acyl chain insertion of the lipid A moiety. PMID- 8499474 TI - Kinetic study of A-type current inactivation in Lymnaea neurons. AB - Macroscopic inactivation of A-current was studied in internally perfused Lymnaea neurons under voltage clamp conditions. Inactivation kinetics were satisfactorily described by the sum of two exponentials, suggesting the presence of two type inactivation. The kinetics of recovery from inactivation were exponential. The rate constants of the fast phase of inactivation gamma f(V) rose steeply with depolarization exposing the pronounced plateau in the range from -30 to 0 mV. The time course of inactivation in this potential range was more closely approximated with the sum of three exponentially decaying components. Calcium and hydrogen ions strongly affected the fast phase of inactivation. Calcium gave a positive shift of a part of the gamma f(V) curve on the left of the plateau. Raising the pH caused a negative shift of the right-hand branch of the gamma f(V) curve. It was shown that these effects are associated with Ca2+ and H+ binding to some specific sites of the channel protein. Two models give good fits with the experimental data. They include two pathways for fast inactivation. Calcium and hydrogen ions are assumed to selectively affect the voltage-dependent transitions related to these pathways of inactivation. PMID- 8499475 TI - Stimulation of microsomal chemiluminescence by ferritin. AB - The ability of ferritin to catalyze rat liver microsomal chemiluminescence was determined in the absence and presence of the redox cycling agent paraquat, and with either NADPH or NADH as reductant. Microsomal chemiluminescence was used as a index of lipid peroxidation. In the absence of added ferritin, NADPH-dependent microsomal light emission was 4-fold greater than the NADH-dependent reaction, and was not sensitive to superoxide dismutase, catalase or DMSO. Ferritin stimulated NADPH-, but not NADH-dependent chemiluminescence in a time- and concentration-dependent manner. The stimulation by ferritin was completely sensitive to superoxide dismutase, but not to catalase or DMSO, suggesting the requirement for superoxide to mobilize iron from ferritin. An iron ligand was not required for the stimulation by ferritin; the addition of certain ligands such as EDTA, DETAPAC or desferrioxamine resulted in inhibition of the stimulation by ferritin. Paraquat potentiated the effect of ferritin on microsomal chemiluminescence with NADPH as cofactor and was weakly stimulatory with NADH. The potentiation by paraquat plus ferritin was prevented by superoxide dismutase and was further elevated by ligands such as ATP. Chemiluminescence proved to be a more sensitive parameter than production of thiobarbituric acid-reactive components to evaluate the stimulation of oxygen radical production by iron released from ferritin, in the absence or in the presence of paraquat. PMID- 8499476 TI - Trichoderma reesei has no true exo-cellulase: all intact and truncated cellulases produce new reducing end groups on cellulose. AB - Adsorption to and formation of insoluble reducing end groups on cellulose was studied for intact enzymes and catalytic domains, 'cores', of the four major cellulases from Trichoderma reesei, CBH I, CBH II, EG I and EG III. Individual enzymes were incubated with NaBH4-reduced, phosphoric acid swollen Avicel (regenerated cellulose) or with filter paper. Adsorption onto regenerated cellulose was rapid (equilibration reached within 2 min), but was slow onto filter paper (not completed after 24 h). On both substrates, less was bound of the core domains than of the intact enzymes. After reaching a maximum in adsorption, all the core domains except CBH I core were released again. In general, the desorption of the core enzymes was much faster than the rate of substrate conversion. All enzymes produced new reducing end groups on both substrates, and thus none of them is a true exo-cellulase. However, both the rate of formation and the amount was considerably higher for the EG enzymes than for the CBH's, which may justify the classification of cellulases into two groups, although the difference is quantitative rather than qualitative. EG III was the most endo-active of the enzymes, and CBH I the least. PMID- 8499477 TI - Dielectric measurements on electro-manipulation media. AB - The permittivity and conductivity of solutions of sugars and sugar alcohols, such as are suitable for electric-field work on cells, were measured. The range of concentrations was 0-3 M (subject to solubility), and the frequency range was that commonly used in dielectrophoresis prior to electrofusion (200 kHz-2 MHz). This was widened to 30 kHz-12 MHz, when dispersive behaviour was found. A parallel-plate impedance chamber with variable electrode-spacing, suited to stable measurements in these low-conductivity aqueous media, was used. Errors due to electrode polarisation were effectively removed by linear regression of the series parameters against electrode distance, as well as by subtraction of data obtained on KCl solutions of comparable conductivity. The permittivity of the sugar solutions decreased as only approximately linear functions of concentration, so that a description in terms of both first- and second-order molar dielectric increments (delta 1 and delta 2) provided a better description of the behaviour than a single linear increment (delta). Sugar solutions of concentration of 1.2 M or less showed no change in permittivity or conductivity over the measured frequency range (i.e., were dispersion-free). On the other hand, various high-density media showed dispersion. The stabilised silica sol 'Percoll' showed dispersion over the whole frequency range; solutions of sucrose (at above 1.2 M concentration), as well as of proprietary high-density solutes ('Metrizamide' at above 0.5 M and 'Nycodenz' at above 0.75 M) showed dispersion above 0.6 MHz. Although these media are of interest for electro-manipulation (they can be used to prevent sedimentation), their dispersive properties may make them unsuitable for use with radio-frequency fields. PMID- 8499478 TI - A novel lectin in rabbit serum binds H type 1, H type 2 and N-acetyl lactosamine structures. AB - A novel lectin (RSL) which recognizes blood group H type 1 and type 2 (Fuc alpha 1-->2Gal beta 1-->3/4GlcNAc beta-R), and N-acetyllactosamine (Gal beta 1- >4GlcNAc beta-R) was purified from rabbit serum using affinity chromatography on Synsorb H type 2 beads, gel filtration and preparative polyacrylamide gel electrophoresis. The lectin agglutinated human O type red cells, and the hemagglutination reaction was inhibited by H type 1 and type 2 haptens, N acetyllactosamine and human salivas from secretor individuals. The molecular weight of the lectin was estimated to be approximate 650,000 and 65,000 on Sephacryl S-400 gel filtration and SDS-polyacrylamide gel electrophoresis, respectively. PMID- 8499479 TI - The effect of sequence variations and structure on the cytolytic activity of melittin peptides. AB - The importance of various amino acid residues in melittin for cytolytic function against mammalian cells was assessed by use of a monoclonal antibody to the C terminal region, synthesis of peptide analogues and chemical modification of specific residues. A monoclonal anti-melittin antibody directed to the basic C terminal region inhibited cytolytic activity. Consistent with this, deletion of one of the two Lys Arg sequences at the C terminal end of the peptide reduced cytolysis 8-fold, although significant activity was still present. A similar reduction in activity was also found with a synthetic analogue which had the reverse sequence to melittin. In contrast, when the last 6 residues of the C terminal region were transferred to the N-terminus, a peptide with markedly reduced activity was obtained. Chemical modification of lysine and arginine residues of melittin indicated that lysine was only minimally important for functional activity compared with arginine which was essential. In particular, our results demonstrate that substitution of serine for lysine 7 has no significant effect on the activity of the peptide and suggest that this residue is important only in maintaining the amphipathic helix of the peptide. PMID- 8499480 TI - Phosphate-dependent glutaminase of rat skeletal muscle. Some properties and possible role in glutamine metabolism. AB - A relatively high activity (26.7 nmol/min per mg mitochondrial protein) of phosphate-dependent glutaminase (EC 3.5.1.2; L-glutamine amidohydrolase) was found in rat skeletal muscle (mixed type from hindlegs) mitochondria incubated in 200 mM potassium phosphate (pH 8.2); the activity was lower in rat heart and diaphragm mitochondria. Phosphate-dependent glutaminase was also found in human skeletal muscle mitochondria, but the activity was about 3-5 times lower than in rat skeletal muscle. Multiplying the specific activity of mitochondrial glutaminase by the amount of mitochondrial protein present in 1 g of rat skeletal muscle the maximum glutaminase activity was found to be 0.352 mumol/min per g wet tissue. The rat skeletal muscle enzyme appears to be similar in many respects to phosphate-dependent glutaminase of the kidney (e.g., S0.5 for glutamine, K0.5 for phosphate, the pH activity profile, inhibition by glutamate). These properties make the skeletal muscle enzyme very similar to the 'kidney type' glutaminase isoenzyme of rat tissues. A significant difference between rat kidney and skeletal muscle enzymes is their adaptive response during acidosis. While the kidney enzyme increases during acidosis, the skeletal muscle glutaminase activity does not. A possible role of glutaminase in the glutamine metabolism in rat skeletal muscle is discussed. PMID- 8499481 TI - Isolation, partial characterization and complete amino acid sequence of the toxic phospholipase A2 from the venom of the common viper, Vipera berus berus. AB - A basic, toxic phospholipase A2 was purified from the venom of Vipera berus berus (Vbb) by a single purification step, using hydrophobic chromatography. The primary structure of isolated protein was established from peptides generated by Gly-specific papaya proteinase IV, beta-trypsin, CNBr and mild acid hydrolysis. The enzyme consists of a single chain of 122 amino acid residues with 14 Cys in positions characteristic for the phospholipase A2 subgroup IIA. As far as we know, this is the first complete Vipera berus phospholipase A2 amino acid sequence reported. PMID- 8499482 TI - Nitrogen metabolism during liver regeneration. AB - Nitrogen metabolism was investigated in regenerating liver-bearing rats through the following parameters: (1) liver aminoacid content, (2) plasma and urinary urea and creatinine, (3) plasma and urinary oxypurines, uric acid and allantoin. Two groups of aminoacids were considered: (1) the essential aminoacids (phenylalanine, tyrosine, isoleucine, lysine, leucine, valine, arginine, histidine and methionine); (2) the non-essential aminoacids (aspartic acid, asparagine, glutamic acid, glutamine, alanine, glycine, serine, threonine and proline). Some of the first group tended to decrease, and those of the second group to increase, immediately after partial hepatectomy. Few ketogenic aminoacids are probably oxidized to provide energy. The flux of aminoacids for gluconeogenesis is minutely controlled, therefore, those of the second group being spared at first and set aside for protein synthesis, which increases on the second and third days after partial hepatectomy. Plasma and urinary urea, oxypurines, uric acid and allantoin did not show any significant variations after partial hepatectomy. The conclusion emerging from the present research is that, although variations in aminoacid composition and metabolism and in purine nucleotide metabolism have been demonstrated to occur in the regenerating liver, the overall nitrogen catabolism, as reflected by the principal end products, does not undergo substantial variations. The remaining liver is able to fulfil this function. PMID- 8499483 TI - An analysis of intracellular 23Na relaxation using the double-quantum filtered NMR signal from the perfused rat salivary gland. AB - The intracellular sodium of the perfused rat mandibular salivary gland was measured by double-quantum filtered 23Na-NMR spectroscopy at 2.34, 4.7 and 8.45 T. Biexponential relaxation of the intracellular 23Na signal was observed, and its intensity was increased by administration of acetylcholine with ouabain at 25 degrees C. The transverse and longitudinal relaxation rate constants were determined by the 'transverse experiment' (D-90 degrees-tau/2-180 degrees-tau/2 90 degrees-delta-90 degrees-acquire) and the 'longitudinal experiment' (D-180 degrees-tau-54.7 degrees-delta-90 degrees-acquire), respectively. From observed dependencies on B0 and temperature (5-37 degrees C), a possibility of exchange between two populations of intracellular Na+ was suggested. A small fraction of Na+ is in the slow-motion condition (with a quadrupole coupling constant of approx. 1.75 MHz and a correlation time of 6 x 10(-8) s). The major portion of intracellular Na+ is in the extreme narrowing condition with a transverse relaxation rate constant of approx. 100 s-1, which corresponds to a viscosity of approx. 5 cP. PMID- 8499484 TI - HT29-18-C1 intestinal cells: a new model for studying the epithelial transport of drugs. AB - A polarized differentiated subclone of HT29, a human colon carcinoma cell line, was used to measure the passage of drugs across the intestinal epithelium. These cells, HT29-18-C1, when grown on permeable filters, formed tight monolayers of high electrical resistance (> 400 omega cm2). Electron micrographs revealed the presence of numerous apical microvilli and well developed junctional complexes. The transepithelial passage of various drugs was studied: the transepithelial permeability coefficients ranged from 0.8 x 10(-6) cm/s for fluorescein, to 4.8 x 10(-5) cm/s for the most lipophilic molecule, testosterone. For the five compounds tested, there was a coarse correlation between the apparent transepithelial permeability coefficient and the octanol/buffer distribution coefficient. The HT29-18-C1 subclone thus represents a new in-vitro model for studying the intestinal absorption of drugs. PMID- 8499485 TI - Phorbol ester treatment of two megakaryoblastic cell lines, CMK and UT-7, induces specific protein composition changes with non-coincident time-courses. AB - The expressions of platelet-specific glycoprotein(GP)s Ib, IIb and IIIa were analyzed in 2 megakaryoblastic cell lines: CMK and UT-7. Phorbol-12 myristate 13 acetate (PMA) treatment of CMK induced expressions of GPs IIb and IIIa that peaked on the 4th day post-treatment, while treated UT-7 cells showed maximal levels of these GPs during the 6-8th days. Antibody staining to detect the formation of GPIb alpha after PMA induction showed the presence of the intact GP in UT-7 and the degraded form in CMK. In UT-7, synthesis of GPIIb mRNA increased on days 4-6 after PMA treatment, in parallel with the increase of GPIIb. PMA increased the cytoskeletal protein (actin and myosin) contents in both lines, but in contrast to the two GPs, the increase in these proteins started immediately after PMA addition to the cells. Cell surface proteins of CMK and UT-7 cells were rapidly modified after PMA induction. Especially notable were the degradations of 93-kDa and 140-kDa proteins that occurred on days 1-2 after PMA treatment. These studies demonstrate that the expression of platelet-specific proteins shows a different time dependency than the increment of cytoskeletal proteins, indicating that the syntheses of these two classes of proteins are most likely induced through different mechanisms. PMID- 8499486 TI - Induction of metalloproteinase activity in human T-lymphocytes. AB - Matrix metalloproteinases are thought to play major roles in a wide array of normal and pathological processes. These proteinases are involved in the degradation of the extracellular matrix and are believed to facilitate the movement of cells from one site to another. In the current study, we examined the expression of the 92 kDa gelatinase activity (MMP-9) by the human T-lymphoma cell line, HSB. Proteinase activity was greatly elevated when cells were treated with TPA. This induction was initially observed at 6 h post-TPA treatment and continued to increase up to 48 h. Proteinase induction was inhibited by actinomycin D and cycloheximide, indicating that nascent RNA and protein synthesis were required. Staurosporine, an inhibitor of protein kinase C activity, suppressed the TPA-induction of gelatinase activity. Our results suggest that TPA induces the 92 kDa gelatinase activity by activating protein kinase C. TGF-beta also induced proteinase activity, although to a lesser extent than TPA. Several criteria indicate that this enzyme is a member of the family of matrix metalloproteinases: (1) this activity was inhibited by EDTA, 1,10 phenanthroline and TIMP; (2) this activity bound to a gelatin-agarose affinity resin; (3) it has a mass of approx. 92 kDa on SDS-polyacrylamide gels; (4) it cleaves gelatin and (5) the inducible proteinase cross reacts with antiserum to MMP-9. PMID- 8499487 TI - Nitric oxide is produced during TNF killing of U937A cells but does not contribute to the cytotoxic process. AB - Proinflammatory cytokines, including TNF, stimulate nitric-oxide free radical production in a variety of tissues through the induction of the enzyme nitric oxide synthase. As free radicals are considered likely candidates in the cytotoxic action of TNF, we examined nitric oxide production in TNF-sensitive U937A and TNF-resistant U937A/R cells and its potential role in TNF-induced cytotoxicity. TNF stimulated U937A nitrite production through a process that was abolished by the competitive inhibitors of nitric-oxide synthase N-omega-nitro-L arginine methyl ester (NAME) and N-G-monomethyl-L-arginine (NMMA) without inhibition of TNF-induced cytotoxicity. TNF also increased nitrite production in TNF-resistant U937A/R cells. In addition, the cytotoxic action of TNF was independent of L-arginine substrate availability. Thus, although cytokine inducible nitric oxide production is emerging as an effective antitumour mechanism, here, TNF clearly exerted potent antitumour activity against U937A cells through a nitric-oxide-independent mechanism. PMID- 8499488 TI - Coordinate induction of acyl-CoA binding protein, fatty acid binding protein and peroxisomal beta-oxidation by peroxisome proliferators. AB - Acyl-CoA binding protein (ACBP) and fatty acid binding protein (FABP) are important intracellular lipid binding proteins. The purpose of the present experiments was to test the hypothesis that peroxisome proliferators induce ACBP in rat hepatocytes as has been shown previously for FABP. The effects of two structurally dissimilar peroxisome proliferators perfluorodecanoic acid (PFDA) and clofibric acid (CPIB) were examined in primary rat hepatocyte cultures in a chemically defined media. Both compounds alter lipid metabolism in primary rat hepatocytes in a similar fashion, although PFDA is more potent than CPIB at inducing peroxisomal beta-oxidation. In addition, PFDA and CPIB compete with long chain fatty acids for binding to FABP but do not compete with long-chain acyl-CoA esters for binding to ACBP. The concentration of ACBP and FABP was increased in peroxisome proliferator-treated hepatocytes relative to vehicle controls within 48 h of treatment. Evidence is given to support increases in ACBP and FABP mRNA being the cause of the increased protein levels by peroxisome proliferators. In addition, the peroxisome proliferators PFDA, perfluorooctanoic acid and ciprofibrate induced hepatic ACBP following in vivo administration to rats indicating that this phenomena is not exclusive to in vitro systems. Therefore, ACBP appears to be a member of the peroxisome proliferator loci, a group of lipid metabolizing proteins, including FABP, which are regulated by peroxisome proliferators such as fibric acids and perfluorinated fatty acids. PMID- 8499489 TI - Insulin and platelet-derived growth factor acutely stimulate glucose transport in 3T3-L1 fibroblasts independently of protein kinase C. AB - Insulin and platelet-derived growth factor (PDGF) are mitogenic for murine 3T3-L1 fibroblasts. Both these mitogens acutely stimulate glucose transport by 2-4-fold in these cells, evident within minutes of agonist exposure. The tumour promoter and protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) also stimulates glucose transport by 2-3-fold over a similar time frame, suggesting that protein kinase C may be involved in the mitogenic action of insulin and PDGF in this cell line. In an attempt to address this, we have measured intracellular sn-1,2-diacylglycerol (DAG) levels in response to insulin, PDGF and PMA. We show that PDGF and PMA induce a rapid elevation in intracellular diacylglycerol levels, but insulin was without effect. In addition, we have shown that PMA and PDGF, but not insulin, stimulate protein kinase C activity. However, depletion of protein kinase C by overnight exposure to PMA, abolished PMA-stimulated glucose transport but had no effect on insulin- and PDGF-stimulated glucose transport, suggesting that the stimulation of glucose transport by these mitogens does not involve protein kinase C. The use of the selective protein kinase C inhibitor, Roche 31-8220, which inhibited PMA-stimulated glucose transport, but was without effect on insulin- and PDGF-stimulated glucose transport further supports this conclusion. Taken together, these data argue against a role for protein kinase C in the stimulation of glucose transport in 3T3-L1 fibroblasts caused by acute exposure to insulin or PDGF. PMID- 8499490 TI - A newly recognized action of cholecystokinin on pancreatic acini-release of lactate dehydrogenase. AB - In the course of examining the actions of the cholecystokinin octapeptide (CCK-8) on pancreatic acini we found that CCK-8 can stimulate release of the large molecular-weight cytoplasmic protein, lactate dehydrogenase (LDH) by as much as 6 fold. CCK-8-stimulated LDH release is mediated by a CCK-preferring receptor, detectable at 100 pM CCK-8, maximal at 100 nM CCK-8, constant for up to 30 min, reversible, not desensitized, and dependent on oxidative metabolism and incubation temperature but not on calcium in the extracellular medium. This action of CCK-8 is blocked by inhibitors of protein kinases, staurosporine, H-7, H-8 and H-9, but not by calmodulin antagonists, chlorpromazine, trifluoperazine or W-7. This action of CCK-8 on LDH release is not reproduced by TPA, 8Br-cAMP or A23187. Thus, it appears to be mediated by a previously uncharacterized protein kinase or an isoform of protein kinase C that is not maximally stimulated by TPA. PMID- 8499491 TI - Effect of bradykinin on cytosolic calcium in neuroblastoma cells using the fluorescent indicator fluo-3. AB - Neuroblastoma cells were used to examine the effect of chronic exposure to increased concentrations of glucose, galactose, or L-fucose on bradykinin stimulated intracellular calcium release using the calcium indicator fluo-3. Bradykinin caused a concentration dependent increase in the intracellular calcium concentration and phosphoinositide hydrolysis in neuroblastoma cells. Norepinephrine, carbachol, serotonin, and thapsigargin also increased the calcium concentration. Treatment of the cells with 10(-6) M bradykinin exhausts calcium release such that the successive treatment of the cells with norepinephrine, carbachol, or serotonin results in no secondary response. In contrast, bradykinin treatment of the cells following exposure to norepinephrine, carbachol, or serotonin caused a secondary increase in calcium release. These results suggest that several hormone responsive calcium pools may exist in neuroblastoma cells or that norepinephrine, carbachol, or serotonin may not fully stimulate calcium release. Bradykinin-stimulated calcium release is not effected by chronic exposure of the cells to increased concentrations of glucose, galactose, or L fucose. Suggesting that hormone-stimulated calcium release is not an abnormality that develops in neural cells exposed to conditions that mimic the diabetic milieu. In addition, these studies provide evidence that fluo-3 is a good fluorescent indicator for the study of calcium mobilization in cultured neuroblastoma cells. PMID- 8499492 TI - Specific dephosphorylation of phosphopeptides by the yeast alkaline phosphatase encoded by PHO8 gene. AB - Partially purified nonspecific phosphate-repressible alkaline phosphatase from Saccharomyces cerevisiae encoded by PHO8 gene (rALPase), efficiently dephosphorylates phosphohistones and a variety of phosphopeptides. The pho8 mutant, constructed by disruption of the chromosomal counterpart of the PHO8 gene, is lacking in phosphatase activity toward phosphopeptides, confirming that this activity is actually due to rALPase. rALPase activity tested on phosphopeptides is maximum in the pH range 6.5-7.5 and the Km values for these substrates are in the micromolar range, suggesting a possible physiological relevance of this enzyme as a protein phosphatase. rALPase dephosphorylates phosphotyrosyl more efficiently than phosphoseryl peptides, but is poorly active on phosphothreonyl peptides. Its specificity towards synthetic peptides and insensitivity to specific inhibitors and activators of authentic protein phosphatases indicate that rALPase differs from both Ser/Thr- and Tyr-specific protein phosphatases. This conclusion is consistent with the lack of homology with any class of known protein phosphatases. PMID- 8499493 TI - Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: a longitudinal case study using 123I-IMP SPECT. AB - Serial assessments of regional cerebral blood flow were performed using 123I-IMP SPECT in two schizophrenic and three schizophreniform patients with persistent auditory hallucination. The initial SPECT study in the period with prominent auditory hallucination revealed an increased accumulation of 123I-IMP in the left superior temporal area which corresponded to the auditory association cortex. In the follow-up SPECT study performed after clinical improvement, the distribution of 123I-IMP had normalized. One of the case with schizophrenia showed a similar increased uptake of 123I-IMP in the left superior temporal area in the third SPECT scan performed when a psychotic relapse with auditory hallucination occurred. MRI scans in two of the five patients demonstrated reduced volume of the temporal lobes. These findings suggest that the auditory hallucinations in schizophrenia may be involved in functional hyperactivity in the left superior temporal cortex which might be based partly on structural abnormalities in the temporal lobes. PMID- 8499494 TI - Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: relevance to neurodegenerative disease. AB - We studied heat shock protein (HSP) synthesis by cultured human neuroblastoma cells in response to either hyperthermia or high levels of superoxide anion (oxygen free radical). Both treatment modalities resulted in induced synthesis of the same major HSP species with an additive effect on the latter and on cell growth inhibition upon combined treatments. Exposure to superoxide anion in the presence of the free radical scavenging enzymes, superoxide dismutase and catalase improved cell survival and prevented HSP induction. These findings suggest a common mechanism by which various forms of injury, such as hyperthermia, cause HSP induction, that is, via oxidative stress or increased production of oxygen free radicals. Increased expression of some HSPs has been detected in association with the pathological lesions that characterize some neurodegenerative diseases such as the neurofibrillary tangles of Alzheimer's disease. This, in turn, suggests that chronic oxidative stress may play a role in the pathogenesis of these disorders. PMID- 8499495 TI - A quantitative magnetic resonance imaging study of patients with schizophrenia. AB - Twenty patients with schizophrenia and ten normal control subjects underwent magnetic resonance imaging of the brain. The volumes of several brain structures were measured using a computer image analysing system. The schizophrenic patients had significantly smaller left parahippocampal volume and larger left temporal horn volume than the control subjects. A larger body of the right lateral ventricle could be estimated in the schizophrenics, but this difference was not significant. In the patient group a non-significant negative correlation was established between the presence of positive symptoms and the left temporal horn volume. There was no significant correlation between the temporal horn and temporal lobe or medial temporal structures. Our results indicate that the left medial temporal structure or left temporal lobe may be involved in schizophrenia and that temporal horn enlargement does not simply represent volume loss of the surrounding tissue. PMID- 8499496 TI - DSM-III-R personality disorders in outpatients with non-bipolar depression: the frequency in a sample of Japanese and the relationship to the 4-month outcome under adequate antidepressant therapy. AB - We investigated the frequency of personality disorders (PDs) and the relationship between the presence of PD and the 4-month outcome of depression under adequate antidepressant therapy in a Japanese sample of 96 outpatients with non-bipolar major depression. The diagnosis of PD was made using a structured interview method (the Structured Clinical Interview for DSM-III-R Personality Disorders) and after severe depressive symptoms were reduced. Any one kind of PD was found in 54.2% of the sample. The most frequent was avoidant (35.4%), obsessive compulsive (22.9%), narcisstic (18.8%), and dependent (16.7%) PDs. The frequencies of these PDs in our study, except narcisstic PD, were about the same as those reported in previous studies with a matched setting for the PD diagnosis. Compared with patients without PD, a worse outcome was found in patients with PD, especially patients with multiple PDs from multiple PD clusters. There was no evidence that a specific PD or PD cluster especially worsens the outcome of depression. PMID- 8499497 TI - The impact of gender and age at onset on the familial aggregation of schizophrenia. AB - Some recent family studies have shown that the familial risk for schizophrenia is higher in female than in male schizophrenics. It is debated whether the risks for the other disorders, such as schizotypal personality disorder or affective disorders in families of schizophrenics are similarly influenced by the proband's gender. Also, the reason for the effect of proband's gender on the recurrence risk for schizophrenia has not been clarified. This family study (159 probands, 589 first degree relatives) confirms that schizophrenia, but also schizophrenia spectrum disorders were more frequent in families of female compared with male schizophrenics. Neither age at onset in probands nor the interaction between gender and age at onset in probands had a relevant impact on the risk figures in relatives. Affective disorders occurred in families independently of the probands' gender. Aetiological heterogeneity or ascertainment bias may account for the modifying effect of proband's gender in schizophrenia. PMID- 8499498 TI - Mental and somatic health and need for care in octo- and nonagenerians. An epidemiological community study. AB - Mental and somatic illness, utilization of psychosocial facilities and need for care in persons aged 85 years and older were examined. Data were based on a representative community sample (n = 402) of Munich city. A total of 358 (89%) subjects of the sample were interviewed, 42 subjects (10.5%) refused, and 2 persons could not be traced. Dementia and depression had the highest prevalence of mental disorders according to the AGECAT (automated geriatric examination for computer assisted taxonomy) computer program of the Geriatric Mental State Interview. In all, 23.6% of the interviewees fulfilled criteria for depression, 25.4% for dementia. We analysed somatic illness according to mental status, the utilization of psychosocial facilities and need for care with regard to mental and somatic illness. PMID- 8499499 TI - The Zurich Study. XVII. Sexual abuse in childhood. Frequency and relevance for adult morbidity data of a longitudinal epidemiological study. AB - In the course of a 10-year longitudinal investigation of young Swiss adults, childhood sexual abuse was assessed at the age of 30 years. It was reported by 11.5% of women and by 3.5% of men; 56% of the females had been abused by relatives (none of the males), 20% by fathers. Abuse cases tended to be more depressed and anxious; they reported more suicide attempts and more sexual problems than controls and also slightly more psychiatric symptoms and neuroticism. Childhood familial risk factors were more frequent for abuse cases than for controls. Depression at adult age was more strongly connected with early familial risk factors than with early sexual abuse. PMID- 8499500 TI - Prediction of short-term outcome of neurotic-depressive inpatients. Results of an empirical study of 134 inpatients. AB - A study was carried out involving 134 neurotic-depressive inpatients (according to ICD-9) treated with cognitive behaviour therapy and in a subgroup additionally with antidepressants. Using standardized rating instruments, a large set of potential predictor variables was tested. After cross-validation according to the split-half technique, only very few of these proved to be suitable as predictors for the main outcome criteria. These predictors included certain aspects of social functioning before index admission, intensity of depressive symptoms at admission and the degree of self-evaluated mood disturbances three weeks after admission. Several predictors known from the literature could not be reproduced in this study, demonstrating the well-known instability of most predictor findings. On the other side, the predictor profile of the neurotic-depressive patients was quite similar to that found in endogenous depressives, a result which might--together with other findings, such as the response of neurotic depressives to antidepressants--question the traditional subclassification of functional depressive states into these subgroups. PMID- 8499501 TI - Effects of light treatment on sleep structure in seasonal affective disorder. AB - Twelve outpatients with seasonal affective disorder (depression, winter type) were treated by 1 h of bright light exposure for five mornings. The intervention produced a significant reduction in depression scores, but no change was seen in the sleep electroencephalographic variables recorded after light treatment. Significant changes were seen, however, in ratings of subjective sleepiness. The acrophase of the circadian sleepiness rhythm was phase advanced, the mean level of the sleepiness rhythm was diminished, and the mean values of sleepiness scores were reduced at 8 and 10 a.m. This minimal influence of bright light on sleep structure is unlikely to explain the well-documented antidepressant effect. PMID- 8499502 TI - Antibodies to brain tissue in sera of schizophrenic patients--preliminary findings. AB - The sera of 30 patients suffering from schizophrenia (DSM III) and 30 neurological controls were tested for antibrain antibodies in a blind indirect immunofluorescence assay. We found IgG- and IgM-binding in the sera of 22 patients, but only 4 out of the 30 age- and sex-matched controls. The binding was mainly directed to neurons from the frontal cortex and septal areas, areas, which are regarded as important in the development of schizophrenic illness. These preliminary data are presented, to encourage other immunological studies in schizophrenia research. PMID- 8499503 TI - Causal attributions in psychiatric patients. AB - An instrument for a systematic assessment of attributions that psychiatric patients have about their disorder is presented together with some preliminary results, for example on differences between sex and diagnostic groups. The comparison with a sample of (mostly untreated) students demonstrates that causal attributions in psychiatric patients should be assessed with specifically designed instruments. The presented scale may help to investigate longitudinally the course of causal attributions during treatment. PMID- 8499504 TI - The impact of President Clinton's healthcare reform proposal on CRNA practice. PMID- 8499505 TI - Fat embolism syndrome. AB - The fat embolism syndrome is a moderately rare, often fatal, complication of trauma injuries, especially those involving long-bone fractures. The syndrome is a complex of cardiac, respiratory, and neurological symptoms that can initially present in ways that make diagnosis difficult or mimic other disorders. This article reviews the syndrome's pathophysiology, diagnostic signs, clinical manifestations, preventive and supportive measures, and the problems associated with anesthetic management of patients with the syndrome. PMID- 8499506 TI - Comparison of the effect of insulated and noninsulated head covers on heat loss during abdominal surgery. AB - Hypothermia is experienced by all patients undergoing major surgical procedures. Hypothermia can lead to postoperative complications affecting oxygenation with neurologic, immunologic, and metabolic consequences. Current methods of heat conservation used in the operating room include blanket warmers, fluid warmers, and anesthesia circuit warmers. These methods are often inadequate at maintaining a patient's body temperature. The current study used a post-test-only control group design. Subjects in the treatment group had an insulated head cover applied within 1 minute of arrival in the operating room, while those in the control group did not. All subjects had routine heat conservation measures (blanket warmers, fluid warmers, and anesthesia circuit humidifiers). Following induction of anesthesia, subjects' temperatures were measured using an esophageal stethoscope with thermistor probe at 10 and 70 minutes. Results showed no significant differences between groups at either time point. PMID- 8499507 TI - Ketorolac and propofol administration for prevention of nausea and vomiting in patients undergoing minor gynecologic surgery. AB - This clinical review explores the efficacy of the nonsteroidal antiinflammatory agent, ketorolac tromethamine, added to an anesthetic regimen utilizing intravenous propofol. Both agents have been shown to reduce the incidence of nausea and vomiting postoperatively when administered to patients undergoing minor gynecologic surgery. Because the incidence of nausea and vomiting is significantly reduced when ketorolac is used in place of opioids to attenuate postoperative pain, it would appear to be an appropriate choice of agent to use following propofol anesthesia. The use of this combination of drugs may not only reduce the incidence of postoperative nausea and vomiting in patients undergoing minor gynecologic surgery, but could reduce the duration of hospitalization and enhance recovery from anesthesia. PMID- 8499508 TI - [Pathogenic features of the genus Leishmania]. PMID- 8499509 TI - [Disease caused by Mycobacterium kansasii in patients with HIV infection]. AB - BACKGROUND: To describe the clinical features and response to therapy in Mycobacterium kansasii disease among HIV infected patients, an increasing problem in our setting. METHODS: A retrospective survey of all charts from patients with HIV infection with Mycobacterium kansasii infection recorded between April 1985 and December 1991. RESULTS: A total of 13 patients were identified. All of them had clinically significant respiratory tract samples with a definite M. kansasii isolation. Only three had disseminated disease. In all but two cases, CD4 cell count at diagnosis time was lower than 200/mm3. Chest X-ray films showed interstitial pattern (8 cases) or alveolar condensation (3 cases) and lung cavities were seen in 4 patients. All patients with lung disease and one with disseminated disease responded well to anti-tuberculous therapy. CONCLUSION: Mycobacterium kansasii produces disease in advances stages of HIV-induced immunosuppression. The most common primary location is pulmonary, but disseminated forms can also be seen. The infection can be controlled with standard anti-tuberculous therapy. PMID- 8499510 TI - [Estimation of infection by Aspergillus fumigatus in mice infected experimentally by the respiratory route]. AB - BACKGROUND: To evaluate a new chitin detection technique for the quantification of Aspergillus fumigatus infection in organs from air-borne infected mice. METHODS: Different groups of mice were air-borne infected with A. fumigatus spores. The mortality rate was studied as well as the extension of the infection by means of colony counts (UFC) and quantification of chitin . RESULTS: The inhalation of A. fumigatus spores by non-immunosuppressed mice produces a 34% mortality rate, with an initial invasion of lung tissue followed by the spleen, kidneys, heart and liver thereafter. CONCLUSION: The quantification of chitin in involved organs allowed us to estimate the degree of organ-specific fungal infections and perhaps could be an useful method for studying the pathogenesis of A. fumigatus infections. PMID- 8499511 TI - [Usefulness of the API ZYM system for the identification of Legionella sp]. AB - BACKGROUND: The identification of Legionella genus is usually difficult, time consuming, and expensive. We decided to study the usefulness of API-ZYM system (Biomerieux) for Legionella species identification. METHODS: A total of 96 strains (82 from Legionella genus and 14 from other bacterial genus) were included. We studied 19 different enzyme activities and we proceed following the manufacturers directions, with an incubation time for galleries of 4 hours at 37 degrees C. RESULTS: Seventeen out of the 19 enzyme activities were uniformly positive or negative for Legionella sp. Thus, the sensitivity of these activities was 100% in identifying Legionella sp. Valine and cystine-arylamidase gave variable reactions for Legionella sp. strains. When the results of these enzyme test were compared to those of the control strains (Haemophilus influenzae, Pseudomonas aeruginosa) we observed that alkaline phosphatase, esterase, esterase lipase, acid phosphatase and naphthol-AS-BI-phosphohydrolase in one side and esterase, esterase-lipase and leucin-arylamidase in the other side were able to differentiate Legionella sp. strains from P. aeruginosa and H. influenzae, respectively. CONCLUSION: API SYM system is a simple, accurate and reproducible method for the identification of Legionella sp. PMID- 8499512 TI - [Evaluation of a new automated system for the determination of antifungal sensitivity]. AB - BACKGROUND: To evaluate a new semi-automatized system (ATB-Fungus, Bio Merieux, Spain) for antifungal in vitro susceptibility testing in yeast. METHODS: We studied the susceptibility of 91 yeast strains (22 Candida albicans, 18 Candida parapsilopsis, 18 Candida krusei, 17 Candida tropicalis, 11 Candida glabrata, 5 Candida guillermondii) against amphotericin B, flucytosine, ketoconazole, miconazole, econazole and nystatin, by means of "ATB-fungus" and agar diffusion and only against systemic usage antifungal agents by agar-dilution method. RESULTS: The correlation between "ATB-fungus" and diffusion method and agar dilution was 100% for amphotericin B, except for Candida krusei and C. tropicalis strains. This correlation rate was lower for fluocytosine and ketoconazole, without major differences between species. There is an absolute concordance between the system under evaluation and agar diffusion method regarding nystatin. For the two azole drugs remaining (miconazole and econazole) the correlation found for Candida glabrata was 100% and for C. parapsilopsis 95% with agar diffusion method. Candida glabrata was the single species that showed better correlation with all three methods, while major differences were seen with C. krusei and C. tropicalis. CONCLUSIONS: Although "ATB-fungus" seems to be a nearly well standardized method for antifungal susceptibility testing, more studies are required for assessing its reproducibility and also to determine when, how and for which antifungal agents would be a valid procedure. PMID- 8499513 TI - [The western immunoblotting technique in atypical situations of Rickettsia conorii infection. Presentation of 2 cases]. AB - BACKGROUND: During the last few years the application of Western immunoblotting in the study of human infection by Rickettsia conorii has led to the development of a new method of serologic diagnosis of the Mediterranean exanthematous fever. METHODS: The pattern of reactivity of serum samples sequentially obtained in the course of infection versus R. conorii antigens (Malish 7 strain) purified in discontinued density gradient and separated by SDS-PAGE was analyzed by Western immunoblotting. RESULTS: The presence of typical profiles of rickettsial infection similar to those observed in the common forms of presentation of the Mediterranean exanthematous fever was demonstrated in a case of accidental infection transmitted via aerosol and followed by an incomplete clinical picture after the early administration of specific antibiotic therapy and in a patient with signs and symptoms characteristic of Mediterranean exanthematous fever in whom the results of indirect immunofluorescence tests were repeatedly negative. CONCLUSIONS: Western immunoblotting may be a specially useful technique as a complementary procedure in the laboratory to guide in the diagnosis of Mediterranean exanthematous fever in special situations. PMID- 8499514 TI - [The post-antibiotic effect]. PMID- 8499515 TI - [Plantar dermatomycosis in a Guinean patient]. PMID- 8499516 TI - [Prolonged fever and pulmonary lesions in an intravenous drug addict]. PMID- 8499517 TI - [The treatment of pneumococcal meningitis]. PMID- 8499518 TI - [Optimization of the reading of antibiotic sensitivity by microdilution in Pseudomonas aeruginosa from cystic fibrosis using the oxidase test]. PMID- 8499519 TI - [Candida lipolytica, a new opportunistic pathogen]. PMID- 8499520 TI - [Soft chancre and Haemophilus ducreyi: a disease and a microorganism on the rise in Spain?]. PMID- 8499521 TI - [Isolation of Stomatococcus mucilaginosus from blood cultures]. PMID- 8499522 TI - [Campylobacter jejuni sepsis in a patient with HIV infection and chronic hepatopathy]. PMID- 8499523 TI - [Evaluation of blood culture in the diagnosis of tuberculosis and other mycobacterioses in immunocompromised patients]. PMID- 8499524 TI - [Pan-sinusitis with bacteremic cavitated pneumonia caused by group C Streptococcus]. PMID- 8499525 TI - [Empyema caused by Pasteurella multocida resistant to penicillin]. PMID- 8499526 TI - [Isolation of Vibrio alginolyticus in 2 cases of otitis externa]. PMID- 8499527 TI - [Meningococcal bacteremia and reactive arthritis]. PMID- 8499528 TI - [Mobiluncus in a breast abscess]. PMID- 8499529 TI - [An increase in the incidence of pneumococcal meningitis?]. PMID- 8499530 TI - [Primary care intervention in tobacco addiction]. PMID- 8499531 TI - [The primary health care tutor]. PMID- 8499532 TI - [Outbreak of rubella in Puerto de Santa Maria (Cadiz)]. AB - OBJECTIVE: To find the frequency of cases of German measles and its spread according to the variables of age, gender, the position regarding vaccination and time; to identify groups at risk in line with the above variables and find out how efficacious vaccination is. DESIGN: Crossover, descriptive study. SETTING: Catchment area of the Pinillo Chico Health Centre in Puerto de Santa Maria (Cadiz). PATIENTS AND OTHER PARTICIPANTS: Between March and June, 1991, there was an outbreak of 175 cases of German measles in our catchment area. We included in the study 149 of these, for whom an epidemiological index card had been filled out. Cases were defined in line with the CDC criteria of a probable or confirmed case. The frequency of cases for the different groups were calculated and compared using the Chi squared test. MAIN MEASUREMENTS AND RESULTS: More than 95% of those affected were aged between 15 months and 26 years (average age 13). There were only significant gender differences, in proportion to the general population, for the 9 to 11 age-group for girls and 12 to 16 for boys. The frequency of cases was significantly greater in males than in females in the 12 to 16 and 17 to 21 age-groups (p < 0.05); and in females than males in the 9 to 11 group (p < 0.05). The frequency of cases between those vaccinated and those not vaccinated also showed significant differences for all the age and gender groups (p < 0.05). Efficacy of vaccination was 81.51%, being over 70% in all age groups. CONCLUSIONS: Studying outbreaks at the Primary Care level assists the identification of susceptible groups and planning of a course of action. PMID- 8499533 TI - [Undergraduate training in primary health care: 6 years' experience at the University of Alicante]. AB - OBJECTIVE: To assess the opinion of medical students on the teaching offered in the Primary Care context (TOPC). DESIGN: Observational and crossover study. The assessment used an opinion questionnaire. PARTICIPANTS: 296 sixth-year medical students between 1987 and 1992. INTERVENTIONS: The TOPC consisted of four weeks stay in a Health Centre with an eminently practical programme. However this also included hour-long theoretical seminars on the most important Primary Care questions and the student's completion of a research project related to Primary Care. RESULTS: The students expressed satisfaction with the TOPC (average score of 4 out of 5). Moreover this satisfaction increased over the five years (from 3.7 to 4.6, p = 0.0001). They believed the TOPC to be useful (3.6 to 4.7, p = 0.0001) and relevant to their future professional activity (3.1 to 4.6, p = 0.0001). They thought that the tutors were very competent (4 out of 5, with no significant variation) and the Health Centres' teaching facilities suitable (3.8 to 4, with no significant variation). Finally, they considered that TOPC should become a compulsory undergraduate subject (3.9 out of 5). CONCLUSIONS: Medical students give a positive rating to the Primary Care teaching offered and believe it should be integrated into the Medicine syllabus as a compulsory subject. PMID- 8499534 TI - [Hepatitis B vaccination in children and adolescents]. AB - OBJECTIVE: This study's main aim was to investigate the immunogenicity of genetic recombinant vaccine in children and adolescents in Madrid, with the intention of determining the length of protection according to the titer of antibodies. A second aim was that of finding the optimum vaccine dosage, in order to suggest possible courses of action leading to an adequate strategy of vaccination. DESIGN: Crossover study. SETTING: Three educational centres in Madrid. PATIENTS AND OTHERS PARTICIPANTS: 1,184 pupils between 5 and 17 years old. INTERVENTIONS: Each individual was given three doses of Engerix B recombinant vaccine in the deltoid area at 0, 1 and 6 months. The vaccine dosage was 10 micrograms for children under 12 and 20 micrograms for those aged 12 and over. MAIN MEASUREMENTS AND RESULTS: The pre-vaccination markers were determined. A month after completing the vaccination, the titer of antibodies was quantified using the Abbott laboratories' microenzyme-immunoanalysis technique. The overall seroprotection rate was 98.9%. The MGT of the titer of antibodies was 9,283.2 mUI/ml. The seroprotection rates were similar among children under 12. The rates were also similar among those who were 12 or over, with titers of antibodies showing significantly higher in the children aged 12 or over. CONCLUSIONS: Given the good results obtained, we consider that the children will be protected for about 10 years. We suggest that all children and/or adolescents should be vaccinated as a means of controlling Hepatitis B. The recommended dosage for children under 8 is 10 micrograms and for those aged 8 and over, 20 micrograms. PMID- 8499535 TI - [Influence of sex, age, and profession on transient work disability at a health center]. AB - OBJECTIVE: To analyse whether the variables of gender, age and type of job of those in full-time work affect short-term unfitness for work (SUW) in a study undertaken within our health area. DESIGN: A prospective and retrospective study of all the SUW. SETTING: Primary Care. An urban Health Centre. PARTICIPANTS: Those people with full-time jobs registered at the Centre. MAIN MEASUREMENTS AND RESULTS: The entire 1098 certificates of SUW issued in 1990 were processed. The population pyramid and job distribution among those in full-time work was obtained by a random sample of 5% of the active population. When time off for maternity (TOM) was excluded, women accounted for 44.8% of SUW and men 55.2%. There were no significant differences with the percentages these figures represent for the active population as a whole. The number of SUW per 100 people in work was 15.9 for men and 21.5 and 17.4 for women (including and excluding TOM, respectively). The average length of SUW, excluding maternity, was 27.06 days for men and 26.8 for women. On the question of age, those under 19 and over 40 contributed least to the SUW percentage. Additionally, those under 19 and over 60 were the proportions of the population least prone to SUW. On the question of type of job, we found a higher contribution to absenteeism than expected within Groups 3 and 4 and less in Groups 0/1, 5 and 7/8/9. The longest average length of time for SUW was in Group X (84.2 days/SUW). CONCLUSIONS: Excluding TOM, gender does not appear to be a variable that affects SUW. Age group and type of job are variables affecting SUW. It will be necessary to undertake research into whether there are additional social or labour factors which might explain. PMID- 8499536 TI - [Evaluation of the effectiveness of personalized and frequent dietetic counseling in the treatment of obesity]. AB - OBJECTIVE: To evaluate the effectiveness of a nursing intervention (personal and ongoing dietary counselling) on the treatment of obese patients. DESIGN: A quasi experimental intervention study (prospective, randomized, with a control group and non-blind). SETTING: At the Primary Care level: carried out in two General Medical practices in the city of Valls. PATIENTS AND METHODS: A total of 64 obese patients (Body Mass Index > 27) who had not carried out any hypocaloric dieting in the previous 30 days were included in the study. The patients were drawn from both practices. In a random manner, 32 were assigned to the control group and 32 to the intervention group. There were 7 losses: people who did not attend all the appointments. INTERVENTIONS: A standard diet was distributed to the intervention group. They had a fortnightly appointment in the nursing station, where their data were recorded and they received personal dietary counselling. The control group patients were only handed and explained the diet; and given appointments at 2 and 4 months in order to check their weight. MAIN MEASUREMENTS AND RESULTS: The average weight loss at 2 months was 3.9 kg in the intervention group and 2.2 kg in the control group (SD p < 0.05). At four months, the weight loss was 2.9 kg in the control group and 4.5 kg in the intervention group (no SD). CONCLUSIONS: Given the scant difference between the weight losses observed in both groups, the conclusion is that, although they are effective, the efficiency of these types of intervention is low. The resources required are excessive, considering that at the end a weight loss at 2 months of little relevance and at 4 months of no significance, in comparison with the control group, is obtained. PMID- 8499537 TI - [Team cohesiveness: opinions of a group of primary health care professionals from Salamanca]. AB - OBJECTIVE: To assess the view of a group of Primary care professionals on their level of perception of group cohesiveness in their teams' work dynamic. DESIGN: A descriptive and sectional study. SETTING: Four urban health centres in Salamanca with a recognised teaching activity. PARTICIPANTS: Both health professionals and those outside the Health Service, working in Primary Care, who had been members of their teams for more than a year (N = 90). MEASUREMENTS AND MAIN RESULTS: Descriptive statistics and "Chi squared" tests were employed. PARTICIPATION: 72%. A high level of agreement on the need for team work (95.23%). They perceived their group cohesiveness as being very low (84.21% affirmed that they encounter problems of cohesiveness). The main statements concerning this lack of cohesiveness were: "lack of common objectives" (25.5%), "intolerance between workers" (20.13%), "work not shared" (19.46%) and "the taking of decisions individually" (19.44%). The main causes given were: lack of support from Management (23.74%) and too little training for team work (21.58%). CONCLUSIONS: There is a high degree of conviction that the team work model is the most efficacious way of developing Primary Care. However in three of the four teams questioned, there were serious problems preventing the teams' reaching an adequate level of group cohesiveness. PMID- 8499538 TI - [Utilization of a continuing care center by the child population, assessing the need of care delivered by pediatricians]. AB - OBJECTIVE: To discover the paediatric demand at a child health clinic (CHC) and its hourly spread. Based on this, to see if the attendance of paediatricians is justified during the hours covered by the CHC. To evaluate, too, whether consumers properly use the CHC. DESIGN: Descriptive, crossover, non-random study. SETTING: Primary Care. PARTICIPANTS: All children under 14 attended at Soria's urban Primary Care centre between 31 January and 31 March, 1991, by the paediatricians and general practitioners. MEASUREMENTS AND MAIN RESULTS: Paediatricians attended 49.8% of the consultations, which covered 17.7% of the weekly opening-time. Nine per cent of children were breast-fed. The most common reasons for attending were: temperature (48%) and cough (20%). The most common diagnoses were tonsillitis (29.4%), Acute Respiratory Infection (16%) and otitis (12.3%). Emergency treatment was given in 4.5% of cases. Prescriptions were given for 94.7% of cases and 1.6% were referred to hospital. CONCLUSIONS: Paediatric demand is to a high degree occasioned by infectious, respiratory and ENT conditions. The proportion of referrals to hospital and the application of treatment in the Primary Care centre indicate insufficient use by the consumer. On the basis of the present study, we are unable to determine whether the presence of paediatricians is justified or not. PMID- 8499539 TI - [The reflection groups in primary health care. I. Their origin]. PMID- 8499541 TI - [Neuropathic ulcers with torpid course ina diabetic patient. An indication for systematic pelvic echography?]. PMID- 8499540 TI - [Weekly continuing information: Current Contents-On-Diskette]. PMID- 8499542 TI - [Simulated consultation with actors for teaching clinical interviews]. PMID- 8499543 TI - [Ewing's sarcoma as final diagnosis of consultation for shoulder pain]. PMID- 8499544 TI - [Neurinoma as cause of lumbar pain: management of lumbago in primary care]. PMID- 8499545 TI - [Our protocols for chronic patients, are they maximalist or realistic?]. PMID- 8499546 TI - [Total arrhythmia due to atrial fibrillation. The primary care approach]. AB - OBJECTIVE: To evaluate the aetiological understanding of auricular fibrillation, the control of ventricular frequency and treatment with anticoagulant drugs and plasmatic antiaggregants. DESIGN: Descriptive study. SETTING: The study was carried out in the Just Oliveras Primary Care Centre (Basic Health Area) in L'Hospitalet de Llobregat, Barcelona. PATIENTS AND OTHERS PARTICIPANTS: Between May and December, 1991, the clinical records of 59 patients with auricular fibrillation was checked. MEASUREMENTS AND MAIN RESULTS: The predisposing factors found were as follows: arterial hypertension, 34%; alcohol intake, 23%; valvulopathy, 19%; ischaemic cardiopathy, 14%; and other cardiopathies, 10%. The average ventricular frequency found was 83 beats per minute. The most common drugs used were digitalis and amiodarone, this latter either alone or with other drugs. Out of a total of 21 patients suffering valvulopathy, 9 received treatment with coumarin. Of these 5 presented mitral valvulopathy and 3 a double mitral lesion. Eight patients (13.5%) received acetylsalicylic acid and 4 (6.8%) took other plasmatic antiaggregants. We can conclude that hyperthyroidism has little relevance as a cause of TA x AF. Each patient's possibilities for cardioversion were not assessed in depth. There were an excessive number of patients who had not had antiaggregant/anticoagulant treatment. Finally, we consider that amiodarone, given to control ventricular response, is over-used. PMID- 8499547 TI - [A prevalence study of tuberculous infection in the schoolchild population in the 1st year of general basic education in Logrono]. AB - OBJECTIVE: To find the extent and spread of endemic tuberculosis in La Rioja and assess its tuberculosis control programme. DESIGN: Prevalence study. SETTING: Both public and private EGB (general basic education) schools in Logrono. PATIENTS AND OTHERS PARTICIPANTS: All students registered for the first year of EGB. MEASUREMENTS AND MAIN RESULTS: A tuberculin test, consisting of two international units (IU) of PPD-23 with tween 80, was carried out. We obtained a prevalence of tubercular infection of 1.12 +/- 0.58%, with a 95% confidence interval and standard error calculated at 0.29%. CONCLUSIONS: The rate of prevalence of tubercular infection in children doing the first year of EGB in La Rioja is high, as seen in the high rates of incidence and carriers. The findings support the appropriateness of continuing with this type of study, for two reasons. The first is the need to establish the annual risk of infection (ARI) in order to monitor how endemic tuberculosis evolves in our community and assess the tuberculosis control programme. The second reason is that, by checking infected children, it becomes possible to prevent or treat new cases of tuberculosis and find possible unknown sources and future reservoirs of infection. PMID- 8499548 TI - [Primary care research: the content of articles published in scientific journals]. AB - OBJECTIVE: The quantifying, by subject area, of research published in scientific journals on primary health care, in five different cultural/geographic areas. DESIGN: Descriptive study. SETTING: Scientific journals on primary health care. PARTICIPANTS: Original articles published in 1991 in the following journals on primary health care (general practice): Atencion Primaria, Canadian Family Physician, Family Practice, Journal of Family Practice and Scandinavian Journal of Primary Health Care. INTERVENTIONS AND MAIN RESULTS: The classification adopted here was that used in the research into primary health care by the Canadian Association of Family Physicians. The five journals between them published 263 original articles. Articles on organisation and provision of health services constituted 42% of the total; next in frequency were articles on epidemiology (18%) and on psychosocial concerns. Methodological studies and research into training and professional kills represent a scarce 6% and 8% respectively. CONCLUSIONS: The most commonly occurring subject in primary health care research is research on services. In the future it would be desirable to develop other areas (the clinical and psycho-social areas, methodology, and training). PMID- 8499549 TI - [An evaluation study of a scale of diabetological education in primary care]. AB - OBJECTIVE: To devise and evaluate a scale of measurement which would permit evaluation at primary care level, of the knowledge that diabetic patients have of diabetes. Secondly, to ascertain the level of knowledge of the sample of diabetic patients attending the Xixona Health Centre. DESIGN: Non-longitudinal, observational, descriptive study. SETTING: Primary health care (health centre). MEASUREMENTS AND MAIN RESULTS: The degree of internal consistency of the diabetes scale of knowledge (DISK) attained a Cronbach Alpha value of 0.87. The coefficients of correlation of each of the factors--defined a priori (general knowledge, diet, exercise, hygiene and self-regulation)--oscillated between 0.77 and 0.83. The Garret index of corrected difficulty was at 0.64. The homogeneity of each item with the questionnaire showed values above 0.31. The reliability measured by means of the KR20 index was 0.86. The odd-even coefficient of reliability was at 0.89. The mean level of correct answers was 70%. A relation was found between the level of knowledge and the variables age and years the patient had been subject to the condition. No relation was found with the treatment, sex, glycaemia or HbA1C level, nor educational level. CONCLUSIONS: The indices obtained by the scale can be considered to be judiciously acceptable, both in terms of their internal consistency and their ability to characterise. The DISK (ECODI) is, then, a valuable tool in the field of primary health care. PMID- 8499550 TI - [The telephone accessibility of the prior appointment program]. AB - OBJECTIVE: To determine the ease of access by telephone when making medical appointments. DESIGN: Cross-sectional, observational, random sample. SETTING: Primary care, Murcia Region. PATIENTS AND OTHER PARTICIPANTS: Centres with a previous appointments system (n = 25) and a random sample of the 276 practitioners involved (n = 97). We ruled out 4 practitioners for not having a telephone in their outer consulting room. MEASUREMENTS AND MAIN RESULTS: We made telephone calls until we had obtained appointments with each of the practitioners, across three hour blocks. The result was an average of 2,333 calls/appointment, with a deflection of 2,271. The mode and median were 1, and the range 26. We found differences in the distribution of the calls across the three blocks (p < 0.05). Comparing rural centres with urban, we found a lower average number of calls in the first two blocks (p < 0.01). CONCLUSIONS: Telephone accessibility is at an appropriate level, both in rural and urban areas. PMID- 8499551 TI - [The teaching health centers of Barcelona. The opinions of residents]. AB - OBJECTIVE: To examine different aspects of the teaching health centres (THC) in the province of Barcelona as evaluated by the ex-residents (Exc-R) from general practice and community medicine (GP&CM). DESIGN: Descriptive study, gathering information by means of a self-administered postal questionnaire, with an addressed reply envelope. SETTING: Barcelona teaching unit (BTU). PARTICIPANTS: Eighty-one general practitioners whose qualifying years were 1987-89, 1988-90 and 1989-91, and who did their last residents year in the THC of the BTU. MEASUREMENTS AND MAIN RESULTS: There are significant differences (p < 0.05) between the various THC, in terms of: quality of teaching material and library; evaluation of the tutor in terms of attendance of classes and comment on medical histories; and average evaluation of tutor by the Ex-R. CONCLUSIONS: We propose that anonymous evaluations made by residents of their tutors should be generalised and used for, amongst other purposes, maintaining or revoking the accreditations of specific THC or tutors. PMID- 8499552 TI - [Reflection groups in primary health care. II. Some theoretical and technical elements]. PMID- 8499553 TI - [The prevention and treatment of migraine]. PMID- 8499554 TI - [Research on primary care. The process of evaluating proposals presented to the Fondo de Investigacion Sanitaria]. PMID- 8499555 TI - [Triazolam: its handling in primary care]. PMID- 8499556 TI - [Minor surgery in primary care]. PMID- 8499557 TI - [Can the saturation of hospital emergency services be resolved via primary care?]. PMID- 8499558 TI - [Down's syndrome and changes in thyroid function]. PMID- 8499559 TI - [Stevens-Johnson syndrome secondary to carbamazepine]. PMID- 8499561 TI - The relationship between factor VII coagulant activity and factor XII activation induced in plasma by endogenous or exogenously added contact surface. AB - The contribution of various enzymes in the activation of factor VII, determined from the increase in factor VII coagulant activity (VIIc), was investigated following the exposure of citrated plasma to low temperature. The contact system of coagulation was initiated either by the contact surface present in certain plasmas (i.e. plasma from women in late pregnancy) or by micellar stearate added to plasma diluted with an equal volume of buffer (plasma from normal healthy subjects or from women in late pregnancy). With either of the contact surfaces, increase of VIIc and the concentration of enzymes derived from factor XII (XIIa) depended on the potency of the contact surface. The stearate-induced VIIc in diluted plasmas from women in late pregnancy or from normal subjects was inhibited by 60-70% in the presence of anti-factor IX monoclonal antibody. VIIc was not increased in XII-deficient plasma following the addition of stearate. The addition of purified human factor XII to this plasma restored the increase in VIIc and the activation of factor XII. In factor IX-deficient plasma, the stearate-induced increase in VIIc was only 38% of that seen in normal plasma and was restored by the addition of purified factor IX. Similarly in factor XI deficient plasma, the stearate-induced increase in VIIc and the factor XII activation were 48% and 69% of that found in normal plasma. The addition of EDTA (2 mM) did not alter the extent of factor XII activation induced by contact surface, but it did inhibit the rise in VIIc. It is concluded that in the presence of contact surface the activation of factor XII and the sequential activation of factor XI and of factor IX results in the activation of factor VII. Activated factor IX is responsible for the major part of the factor VII activation whereas the rest may be through the direct activation by XIIa. PMID- 8499562 TI - Screening for fibrinolysis inhibitory effect of synthetic thrombin inhibitors. AB - Fibrin plate assay (FPA) and thrombelastography (TEG) were used to assess the antifibrinolytic effects of D-Phe-Pro-Arg-H (1), the prototype of peptide aldehyde inhibitors of thrombin, and two of its more stable derivatives, D-MePhe Pro-Arg-H (2) and Boc-D-Phe-Pro-Arg-H (3). Inhibition of plasmin generation by tissue plasminogen activator, urokinase and streptokinase were studied by both FPA and TEG while that of plasmin could only be examined by FPA. TEG was more sensitive than FPA in general and for the detection of streptokinase inhibition in particular. Derivative (3) was 2-50 times more inhibitory than (1) or (2) depending on the enzyme studied and the assay system used. The thrombin selectivities of (1)-(3) were defined as the thrombin to fibrinolytic enzyme potency ratios. Data obtained by the FPA and thrombin time assay indicated (1) and (2) to be 2-80 times more selective for thrombin than (3). On the other hand, the values determined by TEG and recalcification assay showed the thrombin selectivity of (2) to be two to three times higher than that of (1), and (3) to have no such selectivity. According to TEG studies, (1) and (2) assisted rather than inhibited fibrinolysis by reducing the elasticity of human plasma clots. PMID- 8499563 TI - RGD-containing peptides inhibit adhesion of 293 cells transfected with GpIIb/IIIa to fibrinogen: comparison to inhibition of platelet aggregation. AB - Cyclic RGD-containing peptides caused a dose-dependent inhibition of binding of human embryonic kidney cells transfected with recombinant GpIIb/IIIa (r293 clone B) to human fibrinogen coated on to non-tissue culture plates. The inhibitory activity, IC50, of a panel of seventeen RGD-containing peptides ranged from 0.12 to 89.2 microM. These IC50 values correlated with those determined by the inhibition of platelet aggregation (r = 0.99). Even though there was a correlation, there were differences between the platelet aggregation and the bioadhesion assay. The binding of r293 clone B to fibrinogen was not increased by ADP suggesting that GpIIb/IIIa expressed on the surface of r293 clone B cells may be in the 'activated' form. Moreover, preincubation of r293 clone B cells with a monoclonal antibody (mAb) specific for GpIIIa (4B12) resulted in a dose-dependent decrease of binding to fibrinogen while a mAb specific for GPIIb (2D2) had no effect. Neither of these mAbs inhibited platelet aggregation. The binding of r293 clone B cells to fibrinogen required Ca2+ or Mg2+. This cell-based bioadhesion method can provide a tool for screening potential GpIIb/IIIa antagonists and investigating the interaction of GpIIb/IIIa and fibrinogen not possible with platelet aggregation. PMID- 8499564 TI - A new rat model of arterial thrombosis with a platelet-rich head and an erythrocyte-rich tail: thrombolysis experiments with specific thrombin inhibition. AB - A model for thrombolysis in rats was developed. Repeated, focal external heating was applied to the carotid artery which leads to the development of a cyclic blood flow with slow, steady decreases followed by abrupt increases. When this cyclic blood flow stops spontaneously, the entire arterial segment (approximately 10 mm) can be demarcated with snares to create an arterial thrombus of fixed size, with a platelet-rich head and an erythrocyte-rich tail. The usefulness of the model was tested by evaluating the thrombolysis induced by a low dose of recombinant tissue-type plasminogen activator (rt-PA) alone and rt-PA in combination with standard heparin and recombinant hirudin. Re-canalization of the artery was measured as blood flow and as the residual 125I-radioactivity in the artery at the end of the experiment, resulting from 125I-fibrinogen incorporated during the formation of the thrombus. Both blood flow and 125I-activity measurements show that hirudin, but not heparin in combination with rt-PA, significantly improves thrombolysis, which is in accordance with previous experimental findings. It is concluded that the model, with a thrombus resembling the thrombus found in man after coronary occlusion, enables complicated experiments with thrombolysis frequently performed only in large animals to be performed in rats. PMID- 8499565 TI - Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency. AB - The molecular basis of hereditary type I and type II protein C deficiency was studied in a panel of 14 unrelated Austrian families. By direct sequencing of the nine exons and their splice junctions sequence alterations were found in one of the protein C alleles in all but one subject. In twelve subjects a single alteration was found whereas in one subject one of the protein C alleles carried two sequence abnormalities. Whenever DNA from family members was available (11 of the 14 cases) cosegregation of the protein C deficiency with the mutation was observed. In contrast to what has been found previously in a panel of Dutch patients with hereditary protein C deficiency, none of the 14 mutations occurred in more than one family. Only two of the genetic defects (157Arg-->Stop and 178Arg-->Gln) have been found previously in other geographic locations. These data confirm the large genetic heterogeneity of protein C deficiency. PMID- 8499566 TI - The role of tissue factor in the production of thrombin. AB - Tissue factor is now widely accepted to be the major physiological initiator of blood coagulation. The importance of this protein to normal haemostasis may be inferred from the clinical effects of factor VII deficiency and by the fact that congenital tissue factor deficiency has not been described. Tissue factor is a single polypeptide with an established amino acid sequence that may be divided into cytoplasmic, extracellular and transmembrane regions. There are no close structural similarities with other proteins although tissue factor may be a member of the cytokine receptor family. This paper reviews current knowledge of the role of tissue factor in the production of thrombin with particular reference to its expression, location, control and relevance to haemostasis. PMID- 8499567 TI - Active site and exosite binding of alpha-thrombin. AB - alpha-thrombin possesses at least three independent binding sites for substrate, inhibitor and effector molecules. The S1 subsite of the active site is specific for an arginine side group while S2 is a more extended apolar site. The fibrinogen recognition exosite, which usually operates in concert with catalysis, appears to circumnavigate about a third of the surface, although evidence suggests that recognition of a tetra- or pentapeptide sequence is sufficient. Another highly electropositive region of thrombin, which binds the second kringle of prothrombin through salt bridges, is also most likely the heparin binding site. All three sites display distinct binding modes with different molecules. In the active site, these can arise from different optical enantiomorphs combined with reversal of main chain direction, while in the fibrinogen anion binding exosite, certain peptide side chains (hydrophobic) are tolerated of imprecision or are not relevant for binding or undergo a conformational change in substrate binding. Such apparently indiscriminant behaviour easily accounts for the diversity of thrombin functions at the molecular level. PMID- 8499568 TI - A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis. AB - A heterozygous CGG-->TGG (Arg 15-->Trp) substitution was detected in a family with inherited type II protein C deficiency and recurrent venous thrombosis. The mutation, which co-segregates with the deficiency state, occurs in a conserved pentapeptide within the gamma-carboxyglutamic acid (Gla) domain of the protein. PMID- 8499569 TI - A decade of psychiatric consultation with elderly patients in a Dutch general hospital. AB - A retrospective case study of ten years of psychiatric consultation with elderly in a Dutch general hospital is presented. The number of psychiatric consultations is increasing more than would be expected from admission rates or demographic changes. Of these, 25.4% were diagnosed as suffering from mood disorder and 34.1% from organic mental disorder. Somatic and psychiatric diagnoses alone seem inadequate to describe the severe problems of this specific group of patients. PMID- 8499570 TI - Relationships between social and health factors and depression in old age in a multivariate analysis. AB - This community-based epidemiological survey concerns relationships between social and health factors and depression in a Finnish population aged 60 years or over. A multivariate analysis based on log-linear models is used in this study. The log linear model showed five interactions for the depressed men and eight for the depressed women surveyed. These indicated that the depressive persons had experienced detrimental events either of an interpersonal nature or concerning health status more often than those who were not depressed. A positive connection between life stress and depression was found even though no cause-and-effect relationship could be defined. Social stress factors seemed somewhat important prior to the onset of depression in the women studied, whereas stressful health factors played a significant role for the men. Despite this, the log-linear models for the selected variables used here did not point to a combination of interactions between a high incidence of current social stress factors and a high incidence of stressful health factors during the six-month period prior to the onset of depression. PMID- 8499571 TI - May you live amidst interesting dichotomies--from manifest behavior to molecular biology. PMID- 8499573 TI - Hearing impairment and psychosis. AB - The study explores the relationship between hearing impairment and psychotic illness in twenty hospitalized patients (aged 55-77) using as controls twenty age matched community-based older subjects with no psychiatric illness. All subjects received full psychiatric evaluations and comprehensive audiologic assessments. Data were analyzed by discriminant analysis and ANOVA. Experimental subjects were found to have significantly poorer unilateral pure tone averages (PTA) and significantly poorer bilateral speech discrimination ability than control subjects. Patients with a mood disorder had poorer unilateral PTAs than controls, but did not exhibit significantly poorer speech discrimination. Subjects with specifically paranoid ideation were found to have significantly better left ear speech discrimination than nonparanoid subjects. Our data suggest that hearing impairment should possibly be considered a potential risk factor for the development of psychosis in the elderly. PMID- 8499572 TI - Mental disorders and the use of psychotropic drugs in an 85-year-old urban population. AB - The prevalence of mental disorders was studied in a representative sample of 85 year-olds living in Gothenburg, Sweden, (n = 494). All subjects were examined by a psychiatrist, whose diagnoses were defined according to the DSM-III-R criteria. In the sample, the prevalence of dementia was 29.8%, and of any other mental disorder was 24.3%. Psychotic disorders were present in 4.7%, depressive disorders in 12.6%, and anxiety disorders in 10.5%. Anxiety disorders were more common in women than in men. Of all subjects, 42.5% used a psychotropic drug (men 30.1%, women 47.6%, p < 0.001), 34.2% used anxiolytic-sedatives, 14.0% used antidepressants, and 5.7% used neuroleptics. Women used significantly more anxiolytic-sedatives and antidepressants than did men. Of those with no mental disorders, 29.1% used a psychotropic drug. Although the prescription of psychotropic drugs was high, only one fifth of those with depressive disorders received antidepressant drug therapy and one tenth of those with psychotic disorders received neuroleptics. PMID- 8499574 TI - Alzheimer's disease is rare in Cree. AB - A community survey and subsequent clinical assessment of 192 Cree aged 65 years and over registered in two Reserves in Northern Manitoba identified only one case of probable Alzheimer's disease among eight cases of dementia, giving a prevalence of 0.5% for Alzheimer's disease and 4.2% for all dementias. This contrasted with an age-adjusted prevalence of 3.5% for Alzheimer's disease and 4.2% for all dementias in an age-stratified sample of 241 English-speaking residents of Winnipeg. Although it was not so for all dementias, the difference between the groups for prevalence of Alzheimer's disease was highly significant (p < .001). The age-specific patterns of all dementias in the two groups were significantly different, however (p = .0254). PMID- 8499575 TI - A study of the problems older adults encounter when using a mnemonic technique. AB - This study explored problems older adults experience when using a mnemonic technique known as the method of loci. Older subjects received six hours of imagery, judgment, and relaxation pretraining followed by mnemonic training for either four or six hours (Regular or Extended training, respectively). At the end of training, subjects were given a list of the constituent steps of the method of loci and asked to indicate which, if any, were problematic. The factor structure of the relations among the problems varied according to the length of the training subjects received. Specifically, the factor structure of the difficulties reported by the Regular training group reflected problems with using the steps involved in the application of the method of loci, whereas for the Extended training group the factor structure reflected problems with abilities called upon in using the technique. Thus, even with Extended training, subjects may need additional pretraining to develop specific abilities necessary for the successful application of the mnemonic. PMID- 8499576 TI - Institutional respite care: benefits and risks for dementia patients and caregivers. AB - Thirty-seven dementia patients and their caregivers were studied before and after a two-week in-hospital respite stay. Institutional respite care did not alter behavior problems in dementia patients, nor did changes in performance of activities of daily living (ADLs) by Alzheimer's disease (AD) patients exceed those expected from disease progression. Caregivers exhibited an improvement in burden and depression during the respite study, but levels returned to baseline following the patient's return home. PMID- 8499577 TI - Gender roles in a geriatric therapeutic community. AB - During the years 1983-1989 an action research/intervention study in a 40-bed Finnish home for the elderly had as its goal the development of a modified therapeutic community. This paper focuses on the gender roles. Logistic regression analysis indicated that males (N = 17) were best differentiated from females (N = 38) by extramural functional activity, extramural social passivity, religious neutrality, passivity in contacts with a personal nurse, and better education. These five explanatory variables correctly predicted gender in 84% of the cases. These mild gender differences reflect the traditional sex roles of an agrarian Finnish village and were seen mainly as a positive phenomenon. The findings, and some other gender identity themes in the elderly, also were illustrated by qualitative case material. These data suggested that the therapeutic community of aged people should permit active preservation of even conservative and stereotyped gender roles, thereby aiding in the defense and continuity of their often frail identity. The search for new role elements should be supported as well, however, because some elderly continue to develop their gender roles during their final years. PMID- 8499578 TI - The impact of geriatric medical services on mental state. AB - The purpose of this paper was to determine the impact of geriatric medical services on mental state by reviewing all controlled trials of such services. Two computer data bases were searched for relevant articles published from January 1980 to August 1990, and the bibliographies of retrieved articles were searched for additional references. Eleven reports were located that met the four inclusion criteria: original study, published in English or French, controlled trial (nonrandomized or randomized) of a geriatric medical service, and inclusion of at least one measure of mental state in the study. Ten reports met the validity criteria for intervention studies. There was little evidence that geriatric medical services improved the mental state of aged patients; all trials had limitations in design and measures. These findings challenge mental health professionals in two ways: first, services must be developed to address the apparently unmet mental health needs of aged medical patients; second, research methods must be developed to measure the impact of these services. PMID- 8499579 TI - Comparative hepatic transport of desglycylated and cyclic metabolites of rilmazafone in rats: analysis by multiple indicator dilution method. AB - Rilmazafone (RZ) is an orally active sleep inducer which can be activated to its cyclic form (M1) via the labile desglycylated metabolite (DG). In this scheme, RZ is exclusively metabolized to DG and M1 by aminopeptidases in the small intestine. The concentration of M1 in the systemic plasma after oral administration of RZ has been reported to be higher than that observed after administration of M1, due to the lower hepatic extraction of DG than M1 (Koike et al., Drug Metab. Dispos., 16, 609 (1988)). In the present study, the disposition of DG and M1 in rat liver was investigated, using the multiple indicator dilution method. The hepatic availabilities (F) of DG and M1, assessed from the recovery into the hepatic vein, were 0.16 and 0.07, respectively, which was consistent with the previous in vivo finding that the first-pass elimination of M1 was greater than that of DG. The kinetic analysis based on the distributed model showed that the influx (k'1) and efflux (k'2) rate constants for M1 were larger than those for DG, whereas no significant difference in the sequestration rate constant (k'3) was observed between the two ligands. Based on the concept proposed by Miyauchi et al. (J. Pharmacokinet. Biopharm., 15, 25 (1987)), it was suggested that the determinant factor of the hepatic intrinsic clearance was the influx clearance for both ligands, because the values of k'2 for each ligand were much smaller than the respective k'3 values. It was concluded that the higher plasma concentration of M1 after oral administration of RZ than that observed after administration of M1 is due to the fact that the hepatic uptake of DG is lower than that of M1. PMID- 8499580 TI - Pharmacokinetics of fluvoxamine maleate after increasing single oral doses in healthy subjects. AB - The pharmacokinetics of fluvoxamine after single oral administration of 25, 50, and 100 mg fluvoxamine maleate was studied in a three-way cross-over study in 12 healthy male subjects. Fluvoxamine was administered orally in a solution. For dose-proportionality, AUC, and Cmax-dose relationships were evaluated by linear regression. Plasma concentrations increased in a linear dose-dependent manner in the dose range between 25 and 100 mg; t1/2 and Tmax showed no significant differences among treatments. Fluvoxamine was well tolerated. PMID- 8499581 TI - Nonlinear elimination and hepatic concentration of conjugation-metabolite of valproate in guinea-pigs. AB - The plasma clearance and metabolic rate characteristics of valproic acid (VPA) were studied using guinea-pigs placed on various (0.08-9 mumol ml-1 = 11-1303 micrograms ml-1) steady-state plasma concentrations (Css) by constant intravenous (i.v.) infusion. The total clearance (CL) was significantly decreased at plasma concentration of 0.61 mumol ml-1 (88 micrograms ml-1). The metabolic clearance of VPA was apparently biphasic. The maximum metabolic rate (Vmax) and the Michaelis Menten constant (Km) for the primary (Vmax1, Km1) and the secondary (Vmax2, Km2) pathways were Vmax1 = 1.52 mumol min-1 kg-1, Km1 = 0.15 mumol ml-1, Vmax2 = 24.98 mumol min-1 kg-1 and Km2 = 11.70 mumol ml-1, respectively. The Km1 value was within clinical therapeutic concentration range. The formation of conjugated VPA (cjVPA) metabolite in liver was shown to be saturable. Plasma protein binding of VPA was also nonlinear. The dose-dependent decrease in metabolic clearance was counterbalanced by the increased unbound fraction (fu), resulting in a relatively constant apparent clearance of VPA over a wide concentration range. The hepatic concentration of VPA was not significantly different from the plasma unbound concentration, again over a wide concentration range. The biliary and hepatic concentrations of VPA were not significantly different; but the concentration ratio of cjVPA in bile compared with that of VPA in liver decreased against hepatic concentration of VPA, which suggests a saturable conjugation rate. The Km value estimated from hepatic cjVPA production as a function of plasma VPA concentration was comparable with the Km1 value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499582 TI - Disposition of SK&F L-190144 in rats and monkeys after oral, intravenous or ocular administration. AB - The objective of the study was to investigate the systemic disposition of 14C SK&F L-190144 after single intravenous (10 mg kg-1) and oral (200 mg kg-1) doses to rats and after single intravenous and ocular doses (0.33 mg kg-1) to monkeys. After the intravenous dose, the blood concentration-time profile of 14C-SK&F L 190144 followed a rapid triexponential decline with half-lives of 2.5, 15, and 246 min in rats and 3, 19, and 2520 min in monkeys. The 14C-label in blood was mainly the parent compound. The terminal elimination half-life detected in rats using the urinary excretion rate-time data was 700 min. The total body clearance values were 17.6 +/- 2.1 (mean +/- SD, n = 6) and 1.11 +/- 0.41 (n = 4) ml min-1 kg-1 for rats and monkeys, respectively. Both species had similar values of volume of distribution at the terminal phase, 4 to 6 l kg-1, and similar excretion patterns, approximately 60 per cent and 30 per cent of the dose were excreted in the urine and feces, respectively. 14C-SK&F L-190144 was not absorbed orally in rats with the majority of the dose recovered in the feces. Following ocular administration to monkeys, the plasma drug concentrations peaked at 8 h post-dosing but did not reach a biexponential elimination phase until 18 h post dosing, suggesting slow systemic absorption of drug from the ocular site. The monkeys excreted 42 per cent of the dose in urine and 50 per cent in feces after ocular administration. This increase in fecal excretion compared to the intravenous route of administration may have been due to the slow absorption by the ocular and nasal tissues altering the relative proportions of drug elimination via the renal and hepatic routes, or to a proportion of the dose passing into the gastrointestinal tract and exiting unabsorbed. Study results demonstrate similar excretion patterns and volume of distribution after intravenous administration in both species. The slow terminal elimination phase in monkeys was attributed to the low body clearance. The low oral bioavailability was possibly due to the poor partitioning behavior of the drug (logarithm of partition coefficient -2.6). A significant fraction of the dose was absorbed in the body via the ocular route. PMID- 8499583 TI - Pharmacokinetics and pharmacodynamics of valproate analogs in rats. II. Pharmacokinetics of octanoic acid, cyclohexanecarboxylic acid, and 1-methyl-1 cyclohexanecarboxylic acid. AB - The pharmacokinetics of valproic acid (VPA) and three structural analogs, octanoic acid (OA), cyclohexanecarboxylic acid (CCA), and 1-methyl-1 cyclohexanecarboxylic acid (MCCA), were examined in female Sprague-Dawley rats. All four carboxylic acids evidenced dose-dependent disposition. A dose-related decrease in total body clearance was observed for each test compound, suggesting the presence of saturable elimination processes. Furthermore, the apparent volume of distribution for these compounds was, with the exception of CCA, dose dependent, indicating that binding to proteins in serum and/or tissues may be saturable. Both VPA and MCCA exhibited enterohepatic recirculation, although the degree of recirculation appeared to be dose- and compound-dependent. Significant quantities of both VPA and MCCA were excreted in the urine as base-labile conjugates, presumably representing glucuronides. In contrast, OA and CCA were not excreted in the urine as base-labile conjugates and did not evidence enterohepatic recirculation. CCA displayed apparent Michaelis-Menten kinetics, although the calculated Km was dose-dependent. The results suggest that relatively minor changes in chemical structure have a marked influence on the metabolism and disposition of low molecular weight carboxylic acids. PMID- 8499584 TI - Pharmacokinetics and bioavailability of medroxyprogesterone acetate in the dog and the rat. AB - Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and 10 mg MPA and a single intravenous dose of 1 mg MPA. Rats received single oral doses of 0.2, 1, 5, and 20 mg kg-1 MPA and multiple oral doses (14 daily doses) of 0.2, 5, and 20 mg kg-1 MPA. Dog plasma MPA levels from the intravenous dose were characterized by a triexponential decay with disposition half-lives of 0.3, 1.8, and 21.6 h. A Loo-Riegelman analysis of the dog plasma MPA levels from oral doses indicated absorption was not a simple first-order process. The Weibull Function was used to characterize the absorption kinetics of MPA. The oral absorption of MPA in dogs appears to be dose-linear over the dosage range studied, and the absolute bioavailability was estimated at 27 per cent. Rat plasma MPA levels from single and multiple oral doses were analyzed by a non-compartmental approach. AUC and Cmax values were not dose linear over the dosage range studied; indicative of the self-induced metabolism of MPA. Exposure of similar dosages of MPA to both the rat and the dog resulted in similar plasma profiles and pharmacokinetics. PMID- 8499585 TI - Cocaine disposition in discrete regions of rat brain. AB - It has been proposed that various effects of psychoactive drugs on the central nervous system may be related to the capacity of the drug to selectively concentrate in specific regions of the brain. In rat brain, cocaine effects on striatal and nucleus accumbens dopaminergic systems show quantitative differences. However, the disposition of cocaine in various brain regions has not been reported. In the present studies we examined the cocaine concentrations over time in serum and discrete brain regions of the rat after single intraperitoneal (i.p.) injection. At different time points (5, 10, 20, 30, 60, 120, and 240 min) after i.p. injection of cocaine hydrochloride (10 mg kg-1, free base) the rats were decapitated and cocaine in serum and various brain regions was quantitated by a specific gas liquid chromatographic method. There was large inter-individual variability in different rats at each time-point. The disposition pattern of cocaine in rats after i.p. administration was similar to that observed in humans after intranasal administration. Initial absorption rate was rapid and, on average, the peak levels of cocaine were achieved in 10 min. The cocaine levels remained relatively high over the next 50 min indicating continual absorption, and then declined with a rate such that the levels 4 h after cocaine administration were undetectable in most of the animals. The overall changes in cocaine levels in various brain regions paralleled the serum concentrations. The area under the cocaine concentration-time curve (AUC) revealed more than three fold differences in cocaine accumulation in various brain regions. This unequal disposition of cocaine may be responsible in part for differential biochemical effects in different brain regions. PMID- 8499586 TI - Dual effect of valproic acid on the pharmacokinetics of phenytoin. AB - To evaluate the effects of valproic acid on the disposition of phenytoin, a single dose of 600 mg valproic acid and multiple doses of valproic acid (200 mg four times a day for 5 days) were administered together with a single oral dose of 600 mg phenytoin to 12 young male volunteers. Fraction of unbound phenytoin and the area under curve (AUC) of the total and unbound phenytoin in plasma were compared with the control phase in which only 600 mg phenytoin was given. Valproic acid increased the unbound fraction of phenytoin in both single- and multiple-dose studies by 15 per cent and 41 per cent, respectively. Single-dose valproic acid increased the total AUC of phenytoin by 11 per cent. Multiple-dose valproic acid decreased the total AUC by 7 per cent. Single- and multiple-dose valproic acid increased the unbound AUC by 25 per cent and 18 per cent, respectively, probably due to the inhibition on the metabolizing enzymes. We concluded that there are at least two mechanisms involved in valproic acid phenytoin interaction. Whereas valproic acid displacing phenytoin on the plasma protein decreased the total drug concentration of phenytoin, the enzyme inhibition by valproic acid increased both the total and unbound concentration of phenytoin. The two conflicting mechanisms may result in different effects on the total plasma concentration of phenytoin. Therapeutic drug monitoring based on the total concentration of phenytoin may be misleading when valproic acid is co administered. PMID- 8499587 TI - Increased NGF mRNA expression in denervated rat skin. AB - Using a coupled reverse transcription and competitive polymerase chain reaction protocol, we have measured Nerve Growth Factor (NGF) mRNA expression in adult rat skin following its denervation. By 2-4 days, levels of NGF mRNA were increased approximately 5-10 fold over levels in innervated skin, remaining increased for up to at least 2 weeks. In situ hybridization carried out on skin samples revealed that the NGF message was expressed not only in the distal nerve pathways but also in non-nerve associated cells, such as dermal fibroblasts, and in the basal epidermal layer. Denervated skin evokes a NGF-dependent collateral sprouting from neighbouring intact sensory axons. The new findings indicate that an increased NGF production is associated with the increased availability of NGF in such skin, and that cutaneous nerves have a role in regulating this NGF production. PMID- 8499588 TI - Arachidonic acid augments potassium currents in rat neocortical neurones. AB - We analysed the effects induced by arachidonic acid on voltage-dependent outward currents generated by rat neocortical neurones in culture in the presence of Na+ and Ca2+ channel blockers. These currents, recorded with whole-cell voltage clamping techniques, were presumably carried by K+ and were characterized by an early transient and a late persistent component. Extracellular application of arachidonic acid (50 microM) enhanced both components of the voltage-dependent K+ response by 15-29% (n > 20 cells). These effects were reversible and not observed when a low dose (50 microM) of indomethacin was present in the bath (n = 7 cells). We conclude that one or more of the arachidonic acid metabolites of the cyclooxygenase pathway might be involved in the modulation of outward currents in neocortical cells in culture. PMID- 8499589 TI - BDNF protection of basal forebrain cholinergic neurons after axotomy: complete protection of p75NGFR-positive cells. AB - To elucidate the role of brain derived neurotrophic factor (BDNF) in the protection of cholinergic neurons in the basal forebrain, recombinant human BDNF and as a positive control, human recombinant nerve growth factor (NGF), were infused for 20 days into the lateral ventricle of adult rats with fimbrial transections. BDNF and NGF administration protected cholinergic basal forebrain cells from degenerative changes after axotomy, as assessed with immunohistochemical analysis of the two cholinergic marker proteins ChAT and p75NGFR. Both BDNF and NGF treatment completely prevent the lesion induced loss of p75NGFR-positive cells in the septal area of animals with fimbrial transections. This finding contrasts with the result obtained with ChAT immunohistochemistry, where BDNF treatment protects only part of the population of neurons which disappear following the transections. These findings are compatible with the view that there is a cascade of events induced in cholinergic neurons by the transections, so that ChAT expression is lost before p75NGFR expression, and that BDNF reduces degenerative events in the entire population of cholinergic neurons, maintaining some of them as p75NGFR-positive but ChAT negative cells. PMID- 8499590 TI - Involvement of phospholipase A2 in axonal regeneration of brain noradrenergic neurones. AB - We have previously reported that antidepressants such as desipramine (DMI) induce axonal regeneration of brain noradrenergic neurons. In the present experiments, the role of phospholipase A2 (PLA2) in the regeneration of brain noradrenergic axons was studied. Symmetrical sites of the rat frontal cortex were pretreated with 6-hydroxy-dopamine (6-OHDA). Then, the same cortical site of one hemisphere was infused with DMI, while the corresponding site of the other hemisphere was infused with DMI plus 4-bromphenacyl bromide (BPB), a PLA2 inhibitor. The DMI induced axonal regeneration was attenuated by BPB, while the PLA2 activator melittin induced the regeneration of noradrenergic axons. These findings suggest that activation of PLA2 is involved in the regeneration of brain noradrenergic axons. PMID- 8499591 TI - Vomeronasal epithelial cells of the adult human express neuron-specific molecules. AB - Immunohistochemical localization of three molecular markers, neuron-specific enolase (NSE) and protein gene product (PGP) 9.5 for neurons and neuroendocrine cells, and olfactory marker protein (OMP) for olfactory receptor neurons (ORNs) was investigated in the vomeronasal epithelium (VNE) of adult humans. NSE- and PGP 9.5-immunoreactive cells were identified in the VNE. ORNs in the olfactory epithelium of approximately age-matched controls were immunoreactive for the three markers. Most NSE-immunoreactive cells in the VNE were bipolar and similar in shape to the NSE- and PGP 9.5-immunoreactive ORNs. The results indicate that the adult human VNE contains cells expressing two molecular markers characteristic of neurons and that these cells bear a striking morphological similarity to ORNs. PMID- 8499592 TI - Cortical potentials in humans reflecting the direction of object motion. AB - In the monkey, cortical areas can be localized which are specific for the processing of form, colour, or motion, and it is expected that the human visual cortex is organized in a similar way. The recording of scalp potentials generated by neural activity of underlying cortical areas is a non-invasive method which can be used to study the functional organization of the visual cortex with a high temporal resolution. In the present study we recorded slow cortical potentials from normal subjects to investigate how motion stimuli of variable complexity are processed in human visual cortex. The results show that the pattern of cortical activation is dependent on the type of stimulus. When random dots were moving within the entire stimulus field, or during counterphase flicker, maximal activation occurred over occipital electrode sites. During object motion a pronounced activation is recorded at parietal locations, with the direction of object motion being reflected by the time course of this activation. PMID- 8499593 TI - Calcyclin--Ca(2+)-binding protein homologous to glial S-100 beta is present in neurones. AB - The aim of this work was to confirm the presence of calcylin in brain and to identify calcyclin positive cells. Calcyclin was identified in brain soluble proteins that were bound to phenyl-sepharose in a calcium dependent fashion. Specific antibodies against calcylin were found to stain subsets of brain neurones such as neurones in Ammons horn of hippocampus, granule cells in cerebellum, and neurones in brain stem. Glial cells which contain large amounts of S-100 beta protein were calcyclin negative. These results indicate that calcyclin is present in neurones, but not in glial cells. PMID- 8499594 TI - NMDA antagonists partially protect against MPTP induced neurotoxicity in mice. AB - Recent studies show that N-methyl-D-aspartate (NMDA) antagonists protect against neurotoxicity induced by local injections of 1-methyl-4-phenylpyridinium (MPP+) in both the substantia nigra and the striatum. The present studies examined whether either systemic administration of the non-competitive NMDA antagonist MK 801 or the competitive NMDA antagonists CGP39551 and LY274614 would protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic toxicity in mice. Administration of MK-801, CGP39551 or LY274614 for 24 hours partially but significantly attenuated striatal dopamine (DA) depletions induced by MPTP at both 24 h and 1 week. These results support the hypothesis that MPTP neurotoxicity involves a secondary excitotoxic mechanism mediated by NMDA receptors. Such a mechanism may play a role in the etiology of Parkinson's disease. PMID- 8499595 TI - Memory-related processing of complex sound patterns in human auditory cortex: a MEG study. AB - Responses of the human brain to a complex sound pattern were recorded with a 24 channel magnetometer. The sound pattern consisted of 9 successive 50 ms segments, each with a different frequency. An infrequent change in the frequency of one of the segments elicited a magnetic mismatch response (MMNm) which peaked at about 200 ms after the deviant segment onset and resembled the electrical mismatch negativity (MMN). The equivalent current dipole which best explained the MMNm was located in the supratemporal auditory cortex, suggesting that a memory trace for the sound pattern was stored in that region. PMID- 8499596 TI - Nerve growth factor immunoreactivity in the anterior pituitary of the rat. AB - Nerve growth factor (NGF) has long been recognized for its neurotrophic actions upon sensory and sympathetic neurons of the PNS and upon cholinergic neurons of the CNS basal forebrain. Much evidence, however, suggests that potential reciprocal interactions between NGF and various endocrine systems may also occur. In the present investigation we used immunohistochemical techniques to investigate whether NGF is found within the adult rat pituitary, thereby suggesting a possible interaction within this critical neuroendocrine gland. Our results indicate that NGF immunoreactivity is present only within the anterior lobe of the male and female rat pituitary and is exclusively localized within cells immunoreactive for thyroid stimulating hormone (TSH). PMID- 8499597 TI - NMDA receptors in frog semicircular canals. AB - The effects of competitive (2-amino-5-phosphonovaleric acid) and noncompetitive (Mg2+, ketamine and kynurenic acid) NMDA receptor antagonists were tested in isolated semicircular canals of the frog. All these antagonists reduced the resting firing rate recorded from the whole ampullar nerve of the posterior canal. This suggests that NMDA receptors are present at the cytoneural junctions between hair cells and afferent nerve terminals in frog vestibular organs. PMID- 8499598 TI - The cerebrospinal fluid from patients with prolactinoma promotes neurite growth of sensory neurones. AB - The cerebrospinal fluid (CSF) of patients with hypophysis adenomas was used to investigate its effect on organotypic cultures of dorsal root ganglia (DRG) of 10 11 day old chick embryo. Only the CSF from patients with prolactinoma showed a neurite-stimulating effect compared with other hypophysis adenomas. PMID- 8499599 TI - TGF alpha stimulation of phosphatidylinositol hydrolysis in mesencephalic cultures requires neuron-glia interactions. AB - To elucidate the role of TGF alpha as a growth factor in the developing brain and to obtain information on signal transduction mechanisms mediating these effects, we measured the hydrolysis of phosphatidylinositol (PI) in cultures from fetal rat brain cells. Stimulation of PI breakdown induced by TGF alpha was observed in cultures of mesencephalic cells containing both neuronal and non-neuronal cells, whereas TGF alpha was ineffective in both pure neuronal and pure glial cultures. These findings are compatible with the view that TGF alpha plays a role during brain development and that its actions on PI hydrolysis, requires the presence of neuronal and glial cells. PMID- 8499600 TI - Transient expression of the NR2C subunit of the NMDA receptor in developing rat brain. AB - Pharmacologically distinct NMDA-glutamate receptor subtypes have been reported in brain. We have studied the developmental expression of the mRNA encoding the NMDA receptor NR2C subunit in the rat brain by in situ hybridization. In contrast with the adult where no hybridization signal was detected in the hippocampus, a significant signal was seen in this formation during a restricted developmental period (P7-P14). The labelling covered large parts of the hippocampus including in particular the stratum radiatum, pyramidal and oriens layers of the CA1 area. The role of the NR2C subunit in neonatal NMDA receptor properties is discussed. PMID- 8499601 TI - Modifications of thalamo-cortical circuitry in rats prenatally exposed to ethanol. AB - The present study aimed to investigate the organization of thalamo-cortical connections in adult rats exposed to ethanol during the last week of foetal life. Animals underwent thalamic injections of lectin-conjugated HRP. Results demonstrate that the thalamic-recipient zone of sensorimotor cortex is significantly thinner in ethanol-exposed than in control cases. Animals exposed to ethanol also display aberrant thalamo-cortical terminations in layer 5a. Neurones of origin of cortico-thalamic projections are normally located in layers 5 and 6; they appear quantitatively comparable in control and ethanol-exposed cases. Developmental alterations underlying the establishment of anomalous thalamo-cortical relationships are discussed. PMID- 8499602 TI - MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture. AB - Cultures of hippocampal neurones have been used to study a possible correlation between the pattern of dendritic growth and post-translational modification of Microtubule-Associated Protein 2 (MAP2). During the first three days in vitro, a small increase in the total amount of MAP2 is observed, whereas the level of phosphorylation increases exponentially, being particularly dramatic after three days in vitro. Analysis of dendrite morphology by MAP2 immunofluorescence, revealed a parallel exponential growth in dendrite arborization with maximum rates at the third day of culture. We propose a correlation between dendrite arborization and phosphorylation of MAP2, that could be mediated by the establishment of cell contacts. PMID- 8499603 TI - Anti-neurone antibodies are not characteristic of amyotrophic lateral sclerosis. AB - Autoantibodies, a suggested cause of motor neurone degeneration in amyotrophic lateral sclerosis (ALS), were sought immunohistochemically after applying diluted sera to sections of normal human spinal cord. Serum from a case of paraneoplastic motor neurone disease provided a positive control, giving strong staining of motor neurones for IgG but not IgM. The sera of 11 of 21 ALS patients contained IgG that could bind to motor neurones, but similar antibodies occurred also in 5 of 8 subjects with other nervous system disorders and in 3 of 9 neurologically normal controls. Bound IgM was more weakly stained than IgG, and was seen as often with control as with ALS sera. These findings do not support the notion that humoral autoantibodies mediate neuronal destruction in ALS. PMID- 8499604 TI - Expression of protein kinase C isozymes in rat glial cell line. AB - To study the presence and distribution of various isozymes of PKC in glial cells, immunofluorescent studies were performed on a cortical glial cell line cultured derived from rat cerebral cortex and analyzed by a highly sensitive automated laser cytometric device, ACAS-570 (Adherent Cell Analysis and Sorting). The antibodies tested were against alpha, beta, gamma and epsilon isozymes of PKC, and the catalytic domain (cd), i.e. antibody against the cd to all isozymes of PKC. The data indicate that rat cortical glial cell line expresses at least three isozymes of PKC, epsilon, beta, and alpha, the degree of intensity of immunofluorescence being epsilon > beta > alpha. The immunofluorescence for PKC cd was the most intense. PMID- 8499605 TI - Levodopa toxicity in foetal rat midbrain neurones in culture: modulation by ascorbic acid. AB - Levodopa, a dopamine (DA) precursor administered to patients with Parkinson's disease (PD), produces at 25-200 x 10(-6) M concentrations a dose-dependent reduction of 3H-DA uptake in foetal rat midbrain cultures. Also, a decrease in the number of viable cells and tyrosine hydroxylase (TH) positive neurones, plus disruption of the overall neuritic network are observed concurrently with an elevation of quinone levels in the culture medium. Ascorbic acid (AA), which abolished the quinone overproduction, partially prevented these effects. Though levodopa neurotoxicity in vivo is as yet unproven, AA may reduce vulnerability of endogenous or grafted DA neurones in patients with PD. PMID- 8499606 TI - Characterization of endothelin-A receptors in the cerebral circulation. AB - Endothelin-1 (ET-1), a 21-amino acid peptide produced by the vascular endothelium, mediates contraction. In the present study we demonstrate that both ET-1 (Emax: 238 +/- 29% of potassium contraction) and ET-2 (Emax: 231 +/- 36%) produce strong concentration-dependent contractions of circular segments of guinea-pig middle cerebral artery, whereas ET-3 has only weak effects (Emax: 32 +/- 13%). FR 139317 (10(-6) M), a selective endothelinA (ETA) receptor antagonist, shifted the ET-1 response curve to the right (pD2:7.86 +/- 0.09 with and 8.76 +/- 0.09 without the antagonist) in a competitive manner (pA2 = 6.83). These findings are the first to show the presence of ETA receptors in cerebral vessels. PMID- 8499607 TI - Unsaturated fatty acids induce inhibition of the A1-adenosine receptor in rat brain membranes. AB - We examined the effect of fatty acids (FA) and some other bioactive lipids on A1 adenosine receptor (A1-AR) binding in rat brain membranes using the selective agonist (3H)-N6-cyclohexyladenosine [(3H)CHA]. A significant reduction in ligand binding was observed at micromolar concentrations of unsaturated fatty acid with the following potency: oleic < arachidonic < decosaenoic < linoleic < linolenic acid. The other tested compounds: lysophospholipids, platelet-activating factor (PAF) and GM1-ganglioside were without effect on A1-AR expression. The inhibition with unsaturated FA was non-competitive and partially reversed by albumin. The A1 AR agonist binding inhibition evoked by unsaturated FA in many respects is similar to that observed previously following ischaemia and may be contributory to the increased excitability of post-ischaemic brain. PMID- 8499608 TI - CGRP-immunoreactivity in Merkel cells and nonmyelinated nerve plexuses of dog skin. AB - In dog skin Merkel cells, calcitonin gene-related peptide (CGRP) immunoreactivity was consistently encountered at the subcellular dense-core granule region. The immunogold particles used as a marker for CGRP, were located specifically in and around the dense-core granules. They were also found in the surrounding cytoplasm close to the dense-core granules. Nerve terminals supplying the Merkel cell were CGRP-negative. CGRP-immunoreactive nonmyelinated nerve fibres were also found in the same specimen. These nonmyelinated nerve fibres were ensheathed by Schwann cell cytoplasm. The gold particles were only located in the dense-core granules of the axis cylinders. It is concluded that a CGRP-like substance predominantly accumulates in the dense-core granules of dog Merkel cells as well as in cutaneous nonmyelinated fibres. PMID- 8499609 TI - Responses of cultured adult monkey trigeminal ganglion neurons to capsaicin. AB - The sensitivity of adult primate (Macaca mulatta) trigeminal ganglion neurons to capsaicin was studied using whole-cell recording techniques. Neurons responding to capsaicin (9 out of 14) generated inward currents of up to 3.0 nA (median = 0.23 nA; interquartile range = 1.19 nA) upon drug application measured at -60 mV. Capsaicin-sensitive neurons had longer action potential (AP) durations than capsaicin-insensitive neurons. PMID- 8499610 TI - Genetic aspects of the organization of legumin genes in pea. AB - We have compared physical and genetic maps of the region around the legJ gene in pea. In this vicinity there are four B-type legumin genes, arranged as two close pairs. The detection of a recombination event within this gene cluster allows the orientation of this group of genes within the surrounding linkage group to be determined. The relationship between physical and genetic distances in this region is discussed, as are the implications of this for relating physical and genetic maps elsewhere in the pea genome. PMID- 8499611 TI - Modulation of cellular polyamines in tobacco by transfer and expression of mouse ornithine decarboxylase cDNA. AB - In an attempt to modulate the metabolism of polyamines in plants, Agrobacterium tumefaciens strains were produced which contained either a full-length or a 3' truncated mouse ornithine decarboxylase (ODC) cDNA under the control of the cauliflower mosaic virus 35S promoter. Plants of Nicotiana tabacum cv. Xanthi were used for transformation with these two strains of Agrobacterium. Transformations were confirmed by Southern hybridization and amplification by polymerase chain reaction. Two plants containing the full-length cDNA (ODC-12 and ODC-30) and two containing the truncated cDNA (12701-2 and 12701-31) were selected for further experiments. Northern blot analysis indicated that transcription was occurring and western blot analysis detected a polypeptide of ca. 50 kDa that was unique to the plants transformed with truncated ODC cDNA. In order to distinguish between the native and the mouse ODC in the transformed tissues, enzyme activity was assayed at pH optima for the two enzymes, i.e. pH 8.2 and 6.8, respectively. Substantially higher levels of ODC activity were seen at pH 6.8 (optimum for mouse ODC) in the transformants as compared to the controls. This ODC activity was inhibited by alpha-difluoromethylornithine and anti-mouse ODC antisera in a manner consistent with that reported for the mouse ODC. Analysis of cellular polyamines showed significantly elevated levels (4-12 fold) of putrescine in callus derived from transformed plant tissues as compared to the controls. The modulation of polyamine biosynthesis in plants by these techniques should allow us to further analyze the role of these ubiquitous compounds in plant growth and development. PMID- 8499612 TI - Regulatable endogenous production of cytokinins up to 'toxic' levels in transgenic plants and plant tissues. AB - The effects of expressing a chimeric gene consisting of a soybean heat shock gene promoter and a sequence that encodes an enzyme catalyzing the synthesis of a potent phytohormone, the cytokinin iPMP, have been analyzed in transgenic tobacco plants. The production of cytokinin endogenously produced several effects previously undocumented. The differentiation of shoots independent of exogenous cytokinin from heat-treated transgenic plant leaf explants demonstrates that long term heat treatments do not interfere with complex developmental processes. This extends the potential usefulness of heat shock gene promoters to conditionally express genes during windows of development that span several weeks. PMID- 8499613 TI - GTP-binding proteins in plants. PMID- 8499614 TI - Isolation and characterization of a rice cDNA clone encoding ATP/ADP translocator. AB - We isolated a rice cDNA clone which encodes an open reading frame of 382 amino acids. Its deduced amino acid sequence corresponds to an ATP/ADP translocator protein. Its homology with a maize ATP/ADP translocator was 83.9% in nucleotide sequence, and 90.2% of the amino acid level. Expression of this gene is regulated by such external stresses as salinity and low temperature. PMID- 8499615 TI - Circadian rhythmicity in the expression of a novel light-regulated rice gene. AB - We have identified and analyzed cDNAs corresponding to a single-copy gene from rice, designated lir1, whose expression exhibits dramatic diurnal fluctuations. The cDNAs encode a putative protein of 128 amino acids with no homology to known proteins. Lir1 mRNA accumulates in the light, reaching maximum and minimum steady state levels at the end of the light and dark period, respectively. The oscillations of lir1 mRNA abundance persist after the plants have been transferred to continuous light or darkness. Plants germinated in the dark have very low levels of lir1 mRNA, whereas plants germinated in continuous light express lir1 at an intermediate but constant level. These results indicate that lir1 expression is controlled by light and a circadian clock. PMID- 8499616 TI - Nucleotide sequence of a genomic gene encoding tritin, a ribosome-inactivating protein from Triticum aestivum. AB - A genomic gene of tritin, a ribosome-inactivating protein (RIP) from Triticum aestivum, was cloned using a barley RIP gene as a probe. The 5'-non-coding region has potential TATA boxes and three sequences homologous to the binding sequence of the transcriptional activator protein Opaque-2 which activates maize RIP gene expression. The cloned DNA encoded tritin consists of 275 amino acids with no secretion signal sequence. The coding region of tritin was expressed in Escherichia coli using lac promoter and yielded a protein similar to the native one, as determined by SDS-polyacrylamide gel electrophoresis and immunological analysis. PMID- 8499617 TI - Analysis of nuclear proteins interacting with a wheat alpha/beta-gliadin seed storage protein gene. AB - The promoter region (-524 to -46) of the wheat alpha/beta-gliadin seed storage protein gene was analyzed for interactions with nuclear proteins from developing wheat seeds. Six complexes were detected within the first 165 bp upstream of the transcriptional start site. One of the proteins was a non-sequence specific AT binding protein. The remaining five proteins bound in a sequence specific manner. One (CABP) mapped to a conserved CA-rich element at -134 to -112 while another (PalBP) mapped to an adjacent, palindromic sequence at -112 to -106. Three proteins (CTBPs 1-3) formed complexes at two, independent homologous sites. The activities of four of the binding proteins, CTBPs 1-3 and CABP, exhibited similar patterns of expression during seed development: they first appeared at early to mid stages, reached a maximum at mid stage and subsequently decreased, paralleling the pattern of gliadin mRNA accumulation. The non-specific AT-binding protein was detected at relatively high levels only at mid development. PalBP activity, on the other hand, first appeared at mid stage and was present at a constant level throughout later stages of development. The results suggest that the binding proteins may regulate gliadin expression in an antagonistic manner. PMID- 8499618 TI - Characterization of an ethylene-responsive glutathione S-transferase gene cluster in carnation. AB - In this paper we present the structural analysis of two tightly linked genes from the glutathione S-transferase (GST) gene family in carnation (Dianthus caryophyllus). Southern blot analysis and restriction endonuclease mapping revealed a single cloned region of the carnation genome was highly homologous to the previously characterized ethylene-responsive GST mRNA expressed in flower petals during senescence. Nucleotide sequencing of this region revealed the presence of two tandemly arranged genes designated GST1 and GST2. Comparison of the nucleotide sequences of the cloned genomic region with the previously characterized GST cDNA clone pSR8 revealed that GST1 contains the entire transcription unit in 10 exons interrupted by 9 introns. The transcription unit of GST2 was found to be very similar to GST1 with complete conservation of intron position. In addition, the length and nucleotide sequences of the two genes' introns were highly conserved. GST2 was not completely represented by the cloned genomic region, missing the 3' portion of the transcription unit. Primer extension analysis indicated a single transcriptional start site for transcripts which accumulate in senescing carnation petals. The 5'-flanking sequences of GST1 and GST2 were compared and regions of homology and divergence identified. These upstream sequences were compared with other plant ethylene-responsive genes and GST genes and several sequence motifs of potential importance in the regulation of GST expression were identified. A chimeric gene constructed between -1457 bp of the 5'-flanking DNA of GST1 and the coding region of beta-glucuronidase was found to confer ethylene-inducible expression in flower petals following delivery of the construct into tissue by particle bombardment. PMID- 8499619 TI - Expression, organisation and structure of the genes encoding the waxy protein (granule-bound starch synthase) in wheat. AB - A full-length cDNA clone representing the waxy protein (GBSSI) isolated from a hexaploid wheat developing grain cDNA library has been used to characterise the organisation and expression of the waxy genes in wheat. The genes are organised as a triplicate set of single copy homeoloci on chromosome arms 4AL, 7AS and 7DS. The genes are active throughout grain filling where the main 2.3 kb transcript accumulates to high levels. The 2.3 kb transcript is not expressed in leaves where the presence of a related, but less homologous, transcript of 1.6 kb suggests that a different set of genes operates. Gel analysis and purification of the waxy protein isolated from starch granules, followed by N-terminal amino acid sequencing in conjunction with data from hybrid select translation experiments and sequence analysis of the cDNA, shows that the mature protein has a molecular weight of 60kDa (615 amino acids) and that the preprotein includes a chloroplast/amyloplast transit peptide of 7kDa (75 amino acids). Analysis of the derived amino acid sequence and alignment with five other plant waxy proteins shows that they exhibit substantial homology. The wheat protein differs from all others in that it contains an 11 amino acid insertion towards the N-terminus. The protein contains the conserved motif KTGGL found in other waxy proteins and which has been implicated as the active site in glycogen synthase. PMID- 8499620 TI - Construction of a Chlamydomonas reinhardtii mutant with an intronless psbA gene. AB - Efficient chloroplast transformation systems now available allow the manipulation of the evolutionarily highly conserved psbA gene in the eucaryotic organism Chlamydomonas reinhardtii. Two copies of this gene in the inverted repeat region of the chloroplast genome contain four large group I introns. To analyse possible functions of these introns and to generate a mutant for simplified psbA gene manipulations, a psbA cDNA fragment was introduced into a psbA deletion mutant using the biolistic transformation method. A transformant with no introns in the psbA gene has been obtained and represents the first example of the removal of a complete set of introns from a chloroplast gene. The newly generated strain is photosynthetically competent and contains no detectable recipient genome copies. The loss of all four introns appears to be phenotypically silent. PMID- 8499621 TI - Regulation of vascular integrins. PMID- 8499622 TI - Differentiation and proliferation of hematopoietic stem cells. AB - Available evidence indicates that qualitative changes in hematopoietic stem cells and progenitors, such as the decision of stem cells to self-renew or differentiate, or selection of lineage potentials by the multipotential progenitors during differentiation (commitment), are intrinsic properties of the progenitors and are stochastic in nature. In-contrast, proliferative kinetics of the progenitors, namely survival and expansion of the progenitors, appear to be controlled by a number of interacting cytokines. While proliferation and maturation of committed progenitors is controlled by late-acting lineage-specific factors such as Ep, M-CSF, G-CSF, and IL-5, progenitors at earlier stages of development are controlled by a group of several overlapping cytokines. IL-3, GM CSF, and IL-4 regulate proliferation of multipotential progenitors only after they exit from G0 and begin active cell proliferation. Triggering of cycling by dormant primitive progenitors and maintenance of B-cell potential of the primitive progenitors appears to require interactions of early acting cytokines including IL-6, G-CSF, IL-11, IL-12, LIF, and SF. Currently, this simple model fits our understanding of the interactions of growth factors with hematopoietic progenitors. Naturally the model risks oversimplification of a very complex process. However, because the model is testable, it will hopefully challenge investigators to design new experiments to examine its validity. PMID- 8499623 TI - Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells. AB - The forkhead gene (FKH) regulates morphogenesis in Drosophila. It is the prototype of a new family of transcriptional activators. Partially degenerate oligonucleotides to two conserved amino acid sequences of this family were used to prime a polymerase chain reaction (PCR) amplification of HEL cell cDNA. Two unique clones, designated H3 and H8, were isolated that contained homologies to FKH. A third novel clone, 5-3, was isolated by low stringency screening of a chronic myelogenous leukemia cDNA library using H8 as a probe. H3 and 5-3 are preferentially expressed in restricted hematopoietic lineages, while the expression of H8 was ubiquitous. Southern analysis showed that FKH 5-3 is conserved through yeast, which is rare among tissue-specific transcription factors. The H3 and 5-3 clones provide evidence that FKH family members are present in a tissue-restricted manner in humans. PMID- 8499624 TI - An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation. AB - The 8;21 translocation is one of the most common chromosomal translocations in acute myelogenous leukemia (AML), accounting for 40% of pediatric AML with French American-British (FAB)-M2 morphology. The chromosomal breakpoints have recently been identified at the molecular level and shown to involve the AML1 gene on chromosome 21 and the ETO gene on chromosome 8. Translocation results in the consistent fusion of these genes on the der(8) chromosome, resulting in the production of a novel chimeric gene and message. Using oligonucleotide primers derived from the AML1 and ETO cDNAs, we were able to amplify a specific fusion transcript from 26 of 26 patients with t(8;21) by a reverse transcriptase polymerase chain reaction (PCR) approach. DNA fragments of identical size were generated from each case including two with complex translocations. Studies on the sensitivity and specificity of this approach show that PCR analysis can be used as a rapid, accurate, and sensitive means for detecting this chromosomal abnormality, and for following the patients' response to therapy. PMID- 8499625 TI - The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura. AB - Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due to autoantibody-induced destruction of platelets. Several forms of therapy have been used, including corticosteroids, splenectomy, danazol, and a variety of immunosuppressants. We studied the mechanism of action of some of these treatments by evaluating patients' platelet-associated autoantibodies (PAAb) and platelet count before and serially following therapy. Treatment with corticosteroids, splenectomy, cyclophosphamide, and combination chemotherapy resulted in a progressive decrease in PAAb associated with an improvement in the platelet count, and appeared to act by primarily affecting autoantibody production. Conversely, PAAb levels either remained stable or increased during vincristine or danazol therapy despite improvement in the platelet count, suggesting that the major effect of these agents was decreased platelet removal by the reticuloendothelial (RE) system. PMID- 8499626 TI - Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. AB - The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown. PMID- 8499627 TI - Selection of an HEL-derived cell line expressing high levels of platelet factor 4. AB - A platelet factor 4 (PF4)-expressing cell line, HELNeo, was derived from the human erythroleukemia cell line, HEL. This was achieved by stable transfection of HEL cells with a construct containing the rat PF4 promoter driving the gene coding for resistance to neomycin, followed by selection of neomycin-resistant clones. HELNeo cells were all nonadhering and about 5% of the cells had polyploid nuclei (> or = 8N), as compared with 1% in HEL cells. Immunohistochemistry showed that about 90% of the HELNeo cells contained PF4, whereas only approximately 5% of the HEL cells contained PF4. No significant parallel enrichment was observed for other megakaryocytic markers, such as the glycoprotein complex IIb/IIIa, von Willebrand factor, and platelet activation-dependent granule to external membrane glycoprotein (PADGEM), which were present to a similar extent in both HEL and HELNeo lines. The increased expression of PF4 in HELNeo cells was confirmed by transient expression assays and was associated with a fivefold increase in trans acting factors binding to the PF4 promoter. These cells should be a rich source for purifying trans-acting factors binding to the PF4 gene. Moreover, our study shows how a lineage-specific promoter may be used to generate lineage-specific cell lines from a multilineage hematopoietic cell line. PMID- 8499628 TI - Activin A suppresses proliferation of interleukin-3-responsive granulocyte macrophage colony-forming progenitors and stimulates proliferation and differentiation of interleukin-3-responsive erythroid burst-forming progenitors in the peripheral blood. AB - We examined the effects of activin A on the proliferation and differentiation of immature hematopoietic progenitors prepared from peripheral blood (PB) using methylcellulose and liquid-suspension culture. In a kinetic analysis, colony formation by PB granulocyte-macrophage colony-forming unit (CFU-GM) was delayed in a dose-dependent manner by the addition of activin A only when stimulated with interleukin-3 (IL-3), but not when stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF) plus G-CSF. DNA-synthesizing CFU-GM was increased by IL-3, but this effect was abolished by activin A. In contrast, PB erythroid burst forming unit (BFU-E) was accelerated by the addition of activin A only when exposed to IL-3 plus erythropoietin (Epo), but not when exposed to Epo or Epo plus SCF. DNA-synthesizing BFU-E was increased by IL-3 and activin A, alone and additively in combination. In a mixed culture of myeloid and erythroid progenitors, activin A increased the numbers of BFU-E and CFU-Mix colonies at concentrations of 1 and 10 ng/mL and decreased the number of CFU-GM colonies in a dose-dependent manner. However, in a liquid-suspension culture of erythroid progenitors, activin A decreased total cell count and the percentage of hemoglobin-containing cells only when cells were exposed to IL-3 plus Epo. These results indicate that activin A suppresses the proliferation of IL-3-responsive CFU-GM progenitors and stimulates the proliferation and differentiation of IL-3 responsive BFU-E progenitors, and suggest that activin A acts as a commitment factor of immature hematopoietic progenitors for erythroid differentiation. PMID- 8499629 TI - BCR-ABL gene rearrangement and expression of primitive hematopoietic progenitors in chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is characterized by an initial chronic phase of expanded yet orderly clonal hematopoiesis that is distinguished by the BCR-ABL gene rearrangement. We found that although the mature myeloid compartment in patients with CML was expanded and entirely derived from the dominant leukemic clone, the primitive hematopoietic progenitor compartment did not show a corresponding expansion and was substantially enriched for cells without the BCR ABL gene rearrangement. More importantly, primitive progenitors exhibiting the BCR-ABL gene rearrangement did not express either the BCR-ABL hybrid mRNA or fusion protein (P210). Expression of P210 protein and BCR-ABL mRNA increased with myeloid commitment in vivo as well as with growth factor-induced proliferation and differentiation of the primitive CML progenitors in vitro. This differential expression of BCR-ABL between primitive and mature CML progenitors may explain the expansion of the leukemic clone at the level of mature myeloid progenitors and granulocytes without a concomitant expansion of primitive CML progenitors. Because BCR-ABL mRNA is minimally expressed or may be absent in primitive CML progenitors, these cells may escape detection by reverse transcriptase-polymerase chain reaction and eradication by antisense oligonucleotides targeted against BCR ABL mRNA. PMID- 8499630 TI - Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells. AB - We have used two in vitro models to identify genes whose expression may serve as markers of lineage commitment during the development of hematopoietic stem cells. One system involves the development in vitro of blastocyst-derived embryonic stem cells into embryoid bodies. The second involves culturing of day 3.5 blastocysts in vitro under conditions that support their development into yolk saclike cysts. In both cases, hematopoietic cells arise in a manner that closely mimics the normal process occurring in the yolk sac of the early mouse embryo. We have focused our analysis on the expression of mRNAs for 15 hematopoietic growth factor receptor genes and other genes expressed in a hematopoietic lineage specific manner. Although some growth factor receptor genes are apparently expressed constitutively during in vitro development, there are several classes of genes that undergo a highly consistent pattern of induction in both model systems. Genes induced early include those encoding the shared beta subunits of the interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors; those induced at intermediate times include the c-fms, G-CSF receptor, and CD34 genes; and a gene induced late during in vitro development is the IL-7 receptor gene. The defined temporal order for the expression of these genes suggests that they may be useful as markers for multiple stages in the development of different hematopoietic cell lineages during embryogenesis. PMID- 8499631 TI - Biochemical, immunological, and in vivo functional characterization of B-domain deleted factor VIII. AB - Coagulation factor VIII (FVIII) is a cofactor in the intrinsic pathway of blood coagulation for which deficiency results in the bleeding disorder hemophilia A. FVIII contains a domain structure of A1-A2-B-A3-C1-C2 of which the B domain is dispensable for procoagulant activity in vitro. In this report, we compare the properties of B-domain-deleted FVIII (residues 760 through 1639, designated LA VIII) to wildtype recombinant FVIII. In transfected Chinese hamster ovary (CHO) cells, LA-VIII was expressed at a 10- to 20-fold greater level compared with wildtype FVIII. The specific activity of purified LA-VIII was indistinguishable from wild-type recombinant FVIII and both exhibited similar thrombin activation coefficients. Wildtype recombinant-derived FVIII and LA-VIII also displayed similar timecourses of thrombin activation and heavy chain cleavage. However, compared with wildtype recombinant-derived FVIII, the light chain of LA-VIII was cleaved fivefold more rapidly by thrombin. Addition of purified von Willebrand factor (vWF) did not alter the kinetics of thrombin cleavage or activation of either wildtype recombinant-derived FVIII or LA-VIII. The immunogenicity of LA VIII was compared with wildtype FVIII in a novel model of neonatal tolerance induction in mice. The results did not detect any immunologic differences between wildtype FVIII and LA-VIII, suggesting that LA-VIII does not contain significant new epitopes that are absent in wildtype FVIII. LA-VIII was tolerated well on infusion into FVIII-deficient dogs and was able to correct the cuticle bleeding time similar to wildtype recombinant factor VIII. In vivo, LA-VIII was bound to canine vWF and exhibited a half-life similar to wildtype recombinant FVIII. These studies support that B-domain-deleted FVIII may be efficacious in treatment of hemophilia A in humans. PMID- 8499632 TI - Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state. AB - The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state. PMID- 8499633 TI - Human interleukin-10 can directly inhibit T-cell growth. AB - Human interleukin-10 (IL-10) inhibits T-cell proliferation and cytokine production in the presence of monocytes. In this study, we have investigated whether IL-10 can directly inhibit T cells. Highly purified peripheral blood T cells containing less than 0.1% CD14+ cells and unresponsive to phytohemagglutinin (PHA), were growth-inhibited by IL-10 when stimulated with immobilized OKT3 monoclonal antibody (MoAb; 55.4% inhibition). This effect was neutralized by the murine MoAb 19F1 directed against human IL-10. In addition, IL 10 inhibited by 52.5% the proliferation of a human tetanus toxoid-specific T-cell clone (TM11) induced by immobilized OKT3 MoAb in the absence of antigen presenting function. T-cell growth inhibition by IL-10 did not reflect a cytokine induced change in the kinetics of T-cell response to immobilized OKT3 MoAb, and was observed over a wide range of cell and OKT3 MoAb concentrations. Addition of 1% to 5% monocytes to highly purified peripheral blood T cells resulted in the emergence of proliferation to PHA and to soluble OKT3 MoAb, but did not significantly affect levels of growth inhibition by IL-10 in the presence of immobilized OKT3 MoAb. Similarly, addition of 10% monocytes to the TM11 T-cell clone resulted in the emergence of proliferation in response to tetanus toxoid, but did not significantly influence growth inhibition by IL-10 in the presence of immobilized OKT3 MoAb. When stimulated with immobilized OKT3 MoAb in the absence of accessory cells, T cells secreted IL-2. Secretion of IL-2 under these conditions was inhibited by IL-10 (51.5% inhibition). Thus, IL-10 can directly inhibit growth and IL-2 production in T cells triggered by immobilized OKT3 MoAb in the absence of monocytes. PMID- 8499634 TI - Identification of a distinct low-affinity receptor for human interleukin-4 on pre B cells. AB - Biotinylated interleukin-4 (IL-4) was used to examine IL-4 receptor (IL-4R) expression on a range of human B-cell lines by flow cytometry. Using high concentrations of biotinylated IL-4, we have identified a novel low-affinity IL-4 receptor expressed at high levels on pre-B lines. Expression of this low-affinity receptor did not correlate with detected mRNA levels for the previously cloned receptor or with reactivity of two anti-human IL-4R monoclonal antibodies (MoAb). Radiolabeled IL-4 cross-linking studies using pre-B lines showed a doublet of 65 to 75 Kd in contrast to the 110- to 130-Kd molecule detected on cells expressing the cloned IL-4R. A soluble IL-4 binding protein (IL-4bp) was purified from the supernatants of three pre-B lines expressing the low-affinity receptor on their surface. IL-4bp could block both IL-4-mediated CD23 induction on tonsil B cells and IL-4-induced inhibition of proliferation of the pre-B line JM1. Partial N terminal amino acid sequence was obtained from purified IL-4bp that confirmed this protein to be novel. A 12 amino acid peptide based on the IL-4bp sequence was used to produce a polyclonal antiserum that was reactive with purified IL 4bp, and also bound to the surface of pre-B cells but not to murine CTLL cells transfected with the human IL-4R. Blocking MoAb against the previously characterized high-affinity receptor inhibited IL-4-mediated proliferation of hIL 4R+ CTLL cells but had no effect on IL-4-induced inhibition of JM1 cell proliferation, and only partially inhibited IL-4-mediated CD23 and sIgM induction and proliferation of tonsil B cells. The data presented here provide evidence for a novel cell-surface expressed low-affinity IL-4R that also exists as a biologically active soluble IL-4 binding protein. PMID- 8499635 TI - Fibrin and fibrinogen degradation products with an intact D-domain C-terminal gamma chain inhibit an early step in accessory cell-dependent lymphocyte mitogenesis. AB - Although the low molecular weight degradation products of fibrinogen (FgDP) and fibrin (FbDP) are known to inhibit lymphocyte blastogenesis, the effect of purified macro-molecular FgDP and FbDP (molecular weight, 90 to 200 Kd) is unclear. We have examined the effect of these latter FgDP and FbDP and find that products that contain the D domain inhibit lymphocyte proliferation in response to T-cell mitogens, allogeneic mononuclear leukocytes, and anti-CD3 in vitro. Plasmic digestion of D1 in the absence of calcium with removal of the C-terminal end of the gamma chain or disruption of the gamma-gamma C-terminal cross-link site of D-dimer (DD) by puffadder venom (PAV-D) abrogates their inhibitory potential. Prior incubation of monocytes with DD or D1 inhibits subsequent lymphocyte transformation. Binding studies with radiolabeled DD and PAV-D confirm that monocytes interact only with DD. This specific binding may be competitively inhibited by monoclonal antibodies to CD11b/CD18 or by peptide analogues of the C terminal gamma chain of fibrinogen that mimic the adhesion recognition site of integrins. We postulate that DD and D1 bind to CD11b/CD18 on adherent monocytes and modulate lymphocyte activation. These products are typically present in the plasma of patients with disseminated intravascular coagulation with sepsis and could therefore influence inflammatory processes in vivo. PMID- 8499636 TI - Persistent polyclonal lymphocytosis in human immunodeficiency virus-1-infected patients. AB - In this study we describe the clinical, morphologic, immunologic, and genetic features of a chronic peripheral blood lymphocytosis associated with posttraumatic splenectomy in patients with human immunodeficiency virus-1 (HIV-1) infection. Among a series of 2,365 consecutive HIV-1 seropositive cases investigated, eight patients were selected for the presence of more than 4,000 lymphocytes/mm3. All cases were characterized by a lymphocytosis with cytoplasmic azurophilic granules; in three patients the hematologic picture was superimposable with that of lymphoproliferative disease of granular lymphocytes. Phenotypic analysis of lymphocytes showed a prevalent CD3+CD8+ pattern. In vitro evaluations, including the response to mitogens and interleukin-2 and the cytotoxic assays, showed an unimpaired lymphocyte function in the majority of our patients, even in those with advanced stages of the syndrome. The analysis of the configuration of the T-cell receptor (TCR) beta and gamma genes showed a polyclonal pattern of rearrangement. At the mean follow-up time of 45 +/- 8 months, one patient died of overdose when the clinical conditions were stable; all the other patients are alive, although disease progression was documented in two. Our results indicate that a chronic polyclonal lymphocytosis may be associated with HIV-1 infection; this finding seems to be restricted to patients who have undergone splenectomy. The demonstration of a still uncompromised immune system together with a silent clinical course in the patients under study also suggest that splenectomy per se does not favor an aggressive clinical behavior of HIV-1 infection. PMID- 8499637 TI - Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. AB - The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS. PMID- 8499638 TI - Variability of 11q23 rearrangements in hematopoietic cell lines identified with fluorescence in situ hybridization. AB - We mapped and ordered 17 cosmid, phage, and plasmid clones to chromosome 11, bands q22-q24, using fluorescence in situ hybridization (FISH). We then analyzed four hematopoietic cell lines with 11q23 rearrangements, Karpas 45, SUP-T13, RC K8, and Karpas 422, using these probes. The studies showed that the translocation breakpoints of the Karpas 45 and SUP-T13 cell lines, which were derived from T cell malignancies, were located in the same breakpoint cluster region of the MLL gene as the RS4; 11 cell line and patients with the t(9;11), t(11;19), and t(6;11) described previously. We confirmed that the translocation breakpoint of the RC-K8 cell line was located telomeric to the MLL gene, and found that the derivative 11 chromosome of the Karpas 422 cell line, which had been thought to contain a t(4;11) (q21;q23), was in fact formed through a deletion and an inverted tandem repeat of part of 11q. PMID- 8499639 TI - Propagation of Waldenstrom's macroglobulinemia cells in vitro and in severe combined immune deficient mice: utility as a preclinical drug screening model. AB - Waldenstrom's macroglobulinemia (WM) represents an indolent incurable human B cell tumor. We have successfully established a permanent cell line, WSU-WM, without growth factors or viral transformation, from the pleural effusion of a 60 year-old man with IgM kappa WM. Phenotypic characterization of WSU-WM shows IgM lambda and expression of other B-cell markers. Karyotypic analysis shows a male chromosome complement with several clonal aberrations, including t(8;14)(q24;q32). Molecular characterization shows deletion of kappa and rearrangement of lambda light chain genes indicating a class switching. Both the secretory (s mu) and membrane (m mu) components of IgM are expressed. In addition, the breakpoint on 8q24 is downstream of exon 3 of the c-myc oncogene. WSU-WM grows in liquid culture and soft agar. When cells were injected subcutaneously in immune deficient mice, six of seven SCID mice developed subcutaneous tumors as opposed to three of seven in the athymic nude mice. When a WSU-WM SCID tumor was passaged in vivo in the SCID mice, the take rate was 100%. This xenograft model and a soft agar disk-diffusion assay were used to test the efficacy of standard chemotherapy agents against this tumor in vivo and in vitro, respectively. The cell line and the assays described herein can be used as a model to facilitate the discovery of new therapeutic agents or modalities for this disease. PMID- 8499640 TI - Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias. AB - The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL-1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD-1/BCL-1 proto oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)-associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13) associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation. PMID- 8499641 TI - Autocrine and paracrine growth control by granulocyte-monocyte colony-stimulating factor of acute lymphoblastic leukemia cells. AB - Blast colony assays were performed on freshly obtained bone marrow samples from 19 newly diagnosed or relapsed children with acute lymphoblastic leukemia (ALL) of B lineage to determine the effect of added granulocyte-monocyte colony stimulating factor (GM-CSF). Of the 19 marrow samples tested, 7 responded to GM CSF with a mean increase in ALL blast colonies of 346%. Blast cells from one of the responders chosen for flow cytometric study showed expression of GM-CSF receptors on 38% of cells. These findings prompted us to establish five ALL cell lines of diverse phenotypes to examine the expression of GM-CSF and GM-CSF receptor genes in human leukemia, and to determine the role of GM-CSF in autocrine and paracrine growth control of ALL cells. One line, termed G2, manifested a GM-CSF-mediated autocrine pattern of cell growth with the following features: G2 blast colony growth in a serum-free system without added growth factor was density dependent; exogenous GM-CSF augmented G2 colony formation when the cells were seeded at low density; G2 cells constitutively expressed mRNA for GM-CSF and GM-CSF receptor; G2 cells also produced and secreted measurable amounts of GM-CSF into cell culture supernatant; and, monoclonal anti-GM-CSF antibodies abolished G2 colony growth when added to cultures with cells seeded at low density without growth factors. Of the other four ALL cell lines, three expressed mRNA for GM-CSF receptor and responded in vitro to added GM-CSF with increased blast colony growth; however, none of these four cell lines expressed mRNA for constitutive production of GM-CSF. A fifth ALL cell line lacked receptors for GM-CSF and did not respond in clonogenic assays to added GM-CSF. Thus, a bioregulator of normal hematopoiesis plays a central role in autocrine growth control of G2 ALL cells, and an important paracrine growth-promoting role in three of four other ALL cell lines. PMID- 8499642 TI - gamma-Interferon in multiple myeloma: inhibition of interleukin-6 (IL-6) dependent myeloma cell growth and downregulation of IL-6-receptor expression in vitro. AB - In multiple myeloma, malignant plasma cells from most patients with active disease proliferate spontaneously when cultured for 5 days in vitro. This spontaneous proliferation is related to the endogenous production of interleukin 6 (IL-6), the major myeloma-cell growth factor. A 50% inhibitory dose (100 U/mL) of human recombinant gamma-interferon (hr gamma-IFN) blocked the proliferation of myeloma cells almost completely in all 19 patients analyzed. This inhibition was not caused by suppression of endogenous IL-6 production and was also observed in the presence of an excess of hrIL-6. hr gamma-IFN was also completely inhibitory in four human myeloma cell lines (HMCL) whose growth is totally dependent on the addition of exogenous hrIL-6. This inhibition was associated with a 47% to 73% decrease in membrane IL-6-binding gp80 protein as well as with a 90% decrease in the amount of gp80 mRNA in HMCL. These results are in line with recent reports indicating that gamma-IFN inhibited several IL-6-dependent biologic processes. They suggest a need to reconsider why previous preliminary clinical trials failed to demonstrate a beneficial effect of gamma-IFN in multiple myeloma. PMID- 8499643 TI - Expression of unusual immunophenotype combinations in acute myelogenous leukemia. AB - Immunophenotypes for 272 patients with acute myelogenous leukemia (AML) were analyzed using a panel of 22 antibodies. Numerical evidence for unusual coexpressions (present in normal marrow at < or = 0.1%) of surface markers on > or = 10% of the blast cells was found in 85% of all cases. Asynchronous expression of myeloid differentiation antigens occurred in 70% of the cases. Unusual coexpression of T-lymphoid, B-lymphoid, or natural killer (NK) markers with myeloid markers occurred in 38%, 13%, and 21%, respectively, of all AML cases. Two- and three-color analyses confirmed coexpression in 15 of 15 cases, and indicated that these percentages are an underestimate, because coexpression can be demonstrated in cases without numerical overlap. These data indicate that the unusual coexpression of normal differentiation antigens is a common occurrence in AML. Markers in 12 of 13 patients were similar between presentation and relapse, and in two patients, unusual phenotypes detected at first relapse were shown at second relapse, indicating these immunophenotypes are stable in the majority of AML patients. Significant correlations were found between t(8;21) cytogenetics and coexpression of CD19 with CD15 or CD34, t(9;22) and coexpression of CD19 and CD34, and t(15;17) and coexpression of CD2 and myeloid antigens. Multiparameter fluorescence analysis allows detection of unusual phenotypes when the blast counts are < 5% (classical remission). Analysis of 16 patients in remission indicated the presence of presentation phenotypes in 0.2% to 7.9% of the lymphocyte + blast light scatter region, representing 0.03% to 1.4% of the total nucleated marrow cells. Of the 16 patients with > or = 4 months follow-up after detection of these cells, 6 of 6 patients with > or = 0.2% unusual presentation phenotypic marrow cells have relapsed, while 9 of 10 patients with < 0.2% remain in remission. The detection of cells with the unusual presentation phenotype may reflect residual AML cells, and their increase may predict relapse. PMID- 8499644 TI - Single-cell analysis of Hodgkin and Reed-Sternberg cells: molecular heterogeneity of gene expression and p53 mutations. AB - We have used a single-cell based polymerase chain reaction (PCR) amplification technique to examine the gene expression pattern in single Hodgkin's and Reed Sternberg (H&RS) cells from seven patients with Hodgkin's disease. Single cells were isolated from lymph nodes obtained at diagnosis (5 of 7 patients) or in first or second relapse (2 of 7 patients). Gene expression was examined by hybridization to a panel of 22 cDNA probes. Forty-nine H&RS cells (and 23 CD3+ or CD20+ lymphocytes as controls) from four patients with nodular sclerosing Hodgkin's disease (HD) and one patient each with lymphocyte predominant and mixed cellularity HD were successfully analyzed by PCR. This analysis provides evidence that single H&RS cells can coexpress genes characteristic of several hematopoietic lineages (monocytes and lymphocytes). Genes characteristic of activated lymphoid cells are expressed in most H&RS cells. Heterogeneity of expression for certain genes between different cases was found and may eventually define molecular subgroups of HD. These findings indicate that H&RS cells of HD resemble activated hematopoietic cells. Phenotypically similar cells from different cases exhibit characteristic molecular differences. In one patient, 5 of 7 single RS cells showed identical p53 cDNA mutations at codon 246 on specific reverse transcriptase [RT]-PCR and sequencing of exons 5 through 8. The novel experimental approach may provide a valuable tool for understanding the molecular events in newly diagnosed Hodgkin's disease and progression of the disease. PMID- 8499645 TI - Appearance of nuclear factors that interact with genes for myeloid calcium binding proteins (MRP-8 and MRP-14) in differentiated HL-60 cells. AB - Myeloid calcium binding proteins MRP-8 and MRP-14 were induced, and their genes were coordinately expressed, during differentiation of human leukemia HL-60 cells into macrophage-like cells after treatment with 1,25-dihydroxyvitamin D3 (VD3). Both MRP-8 and MRP-14 mRNAs appeared on the day after VD3 treatment. Their level reached a peak on day 2, and then quickly declined. Nuclear factors that interact with the 5'-upstream regions of MRP-8 and MRP-14 genes were studied with gel mobility-shift assays. Two factors (MP8FI and MP8FII) that interacted with 379 bp (426-48 bp upstream from the transcription-initiation site of MRP-8 gene) and 67 bp (-47 - +20) DNA fragments, respectively, were found in the cells treated with VD3 for 1 day. MP8FI and MP8FII were present neither in the nuclei of untreated HL-60 cells, nor in the nuclei of the cells treated with VD3 for 6 days. Human monocytic leukemia THP-1 cells, which constitutively expressed MRP genes, had MP8FII but not MF8FI. MP8FII was found to interact with the 19-mer sequence located just upstream of the TATA box. Also, two factors that bound to the different upstream regions (-400 - -150 and -149 - +50) of MRP-14 gene were detected in the differentiated HL-60 cells. One of these, MP14FI, appeared on day 1, but on day 6 its concentration greatly decreased. The other, MP14FII, was found in greater quantity on day 6 than on day 1. MP14FI, but not MP14FII, was found in THP-1 cells. These factors may be involved in the expression of MRP-8 and MRP-14 genes in VD3-differentiated HL-60 cells. PMID- 8499646 TI - Coinduction of granulocyte-macrophage colony-stimulating factor release and lymphokine-activated killer cell susceptibility in monocytes by interleukin-2 via interleukin-2 receptor beta. AB - Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. By a 5-hour 51Cr-release assay, monocytes cultured in IL-2 were found to gain increasing susceptibility to LAK cells with time and this effect was dose dependent. Maximal susceptibility was obtained with a 4-day culture in 1,000 U/mL of IL-2. Monocytes were also found to release GM-CSF in response to IL-2 using a CSF-dependent cell line, Mo7e. Because IL-2-induced GM-CSF release coincides with LAK lysis of IL-2 cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM-CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells. PMID- 8499647 TI - Deoxygenation-induced changes in sickle cell-sickle cell adhesion. AB - The tendency for sickle cells to adhere to each other is increased in oxygenated sickle blood in parallel with cell density. The increased adherence of these cells occurred despite their reduced deformability and diminished ability to form rouleaux. Using a method developed in our laboratory, we measured the yield stress: a sensitive index of cell-cell adhesion of deoxygenated suspensions of sickle cells. Deoxygenation of whole sickle blood to 30 to 50 mm Hg caused a significant increase in yield stress of all sickle blood samples. Deoxygenation caused a significant increase in yield stress of both dense and light sickle cells. Deoxygenation-induced increases in yield stress occurred at higher oxygen tensions for dense (> 55 mm Hg) than for light sickle cells (< 45 mm Hg). The increase in yield stress on deoxygenation was correlated with hemoglobin polymerization as assessed morphologically by sickling or by changes in relative viscosity. Thus, deoxygenation-induced cell sticking must involve small areas of strong membrane adhesion because the changes in yield stress occurred despite a reduction in rouleaux formation and surface area of membrane contact. Sickle trait red blood cells also exhibited increased yield stress on deoxygenation but only under hypertonic conditions where sickling occurred. Thus, deoxygenation induced cell adhesion did not require prior membrane damage because it occurred in sickle trait cells. No change in yield stress was seen when deoxygenated sickle cells were suspended in buffer, but the addition of physiologic amounts of fibrinogen to buffer restored the deoxygenation-induced increase in cell adhesion. We speculate that the increase in sticking among sickle cells on deoxygenation results from spicule formation and may involve interaction of fibrinogen and possibly other plasma proteins with the cell membrane. PMID- 8499648 TI - Characterization of the autologous antibodies that opsonize erythrocytes with clustered integral membrane proteins. AB - In earlier studies we presented evidence that the clustering of the integral membrane protein, band 3, can serve as a signal for immune recognition and clearance of senescent or abnormal erythrocytes from circulation. In this study, we have exploited the capacity of 1 mmol/L Zn+2 to mildly and reversibly cluster band 3 in situ to characterize the nature of the autologous antibodies specific for the clustered state. We report that the autologous IgG elute almost exclusively in a high molecular weight complex with other proteins when C12E8 detergent extracts of Zn clustered membranes are chromatographed on Sepharose CL 6B. The complex was also seen to contain complement component C3, hemoglobin, and a cross-linked oligomer of band 3. Autologous IgG and complement were virtually absent from all other fractions. When the band 3 clusters were disaggregated by removal of the Zn+2, the autologous IgG eluted from the erythrocyte surface. Collection of this IgG and use of the antibody in immunoblots of erythrocyte membranes showed that the band 3 monomer, dimer, and oligomers were the major antigenic species. Except for a minor unidentified band at approximately 78,000 d, no other proteins were significantly stained. Curiously, band 3 showed an uneven staining pattern, with oligomers and the leading edge of the monomers appearing more intensely than expected from their abundances in the Coomassie blue-stained gels. Typing of the same autologous IgG with monoclonal antibodies specific for the different subclasses of IgG showed the presence of only subtypes 2 and 3. Taken together, these data suggest that a specific population of autologous IgG recognizes sites of integral membrane protein clustering (a common lesion in senescent and abnormal red blood cells) and that the antigen within these clusters involves an aggregated state of band 3. PMID- 8499649 TI - Reconstitution of human immunoglobulin VH repertoire after bone marrow transplantation mimics B-cell ontogeny. AB - Reconstitution of the human Ig repertoire after allogeneic and autologous bone marrow transplantation (BMT) was followed by analysis of the expression of the six VH families using in situ hybridization on BM cells at 30, 60, and 90 days postgraft. Our results indicate that during the early post-transplantation period, the expressed repertoire of VH is dramatically affected: VH3, the major expressed family in adult B cells, is decreased two- to threefold and is compensated by transient overexpression of the other families, especially VH4, VH5, and VH6. Similar results were observed in allogeneic and autologous grafted patients. Kinetics of reconstitution mimics normal repertoire development described in ontogeny, although normalization, as compared with the adult pattern, may take as long as 1 year. PMID- 8499650 TI - Favorable treatment outcome in children with acute myeloid leukemia and Down syndrome. PMID- 8499651 TI - Characterization of 24 porcine (dA-dC)n-(dT-dG)n microsatellites: genotyping of unrelated animals from four breeds and linkage studies. AB - Twenty-four PCR primer pairs were designed for the detection of porcine microsatellites. Polymorphism was investigated in 76 unrelated animals from four different breeds: Duroc, Landrace, Hampshire, and Yorkshire. Compared with human microsatellites, a general lower heterozygosity was detected; however, for each microsatellite a significant variation between breeds in number of alleles and heterozygosity was seen. Mean heterozygosity was found to be significantly higher (P < 0.01%) in the Yorkshire breed than in the other three breeds. Linkage analyses with the CEPH linkage packet were performed in a backcross family comprising 45 animals, of which 43 had informative meioses. Ten of the microsatellites could be assigned to six different linkage groups, demonstrating that linkage mapping with microsatellites can be carried out with great efficiency in a relatively small number of animals. Four of the linkage groups represent Chromosomes (Chrs) 4, 6, 7, and 8 respectively, while two linkage groups are unassigned. PMID- 8499652 TI - Targeted cloning of a subfamily of LINE-1 elements by subfamily-specific LINE-1 PCR. AB - Subfamily-specific LINE-1 PCR (SSL1-PCR) is the targeted amplification and cloning of defined subfamilies of LINE-1 elements and their flanking sequences. The targeting is accomplished by incorporating a subfamily-specific sequence difference at the 3' end of a LINE-1 PCR primer and pairing it with a primer to an anchor ligated within the flanking region. SSL1-PCR was demonstrated by targeting amplification of a Mus spretus-specific LINE-1 subfamily. The amplified fragments were cloned to make an SSL1-PCR library, which was found to be 100-fold enriched for the targeted elements. PCR primers were synthesized based on the sequence flanking the LINE-1 element of four different clones. Three of the clones were recovered from Mus spretus DNA. A fourth clone was recovered from a congenic mouse containing both Mus spretus and Mus domesticus DNA. Amplification between these flanking primers and LINE-1 PCR primers produced a product in Mus spretus and not in Mus domesticus. These dimorphisms were further verified to be due to insertion of Mus spretus-specific LINE-1 elements into Mus spretus DNA and not into Mus domesticus DNA. PMID- 8499653 TI - Assignment of the rat genes coding for dopa decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2). AB - By use of rat cDNA probes and a panel of cell hybrids segregating rat chromosomes, the genes encoding three pyridoxal 5'-phosphate (PLP)-dependent decarboxylases--namely, DOPA-decarboxylase (Ddc), glutamic acid decarboxylase 1 and 2 (Gad1 and Gad2)--were assigned to rat Chromosomes (Chrs) 14, 3, and 17, respectively. If one takes into account chromosome localizations in the human and the mouse, the present results (i) show that a synteny group is retained on rat Chr 14, human Chr 7, and mouse Chr 11 (Ddc); (ii) strengthen the homology relation known between rat Chr 3 and human and mouse Chrs 2 (Gad1); (iii) suggest that rat Chr 17 has no extensive homology to any human chromosome; and (iv) suggest the order (Prl, Fdp)--Tpl2--Gad2 on the rat Chr 17. PMID- 8499654 TI - Mapping of the beta-lactoglobulin gene and of an immunoglobulin M heavy chain like sequence to homoeologous cattle, sheep, and goat chromosomes. AB - With a combination of non-isotopic in situ hybridization and simultaneous fluorescent R-banding, this study presents the first map of the short arm of sheep Chromosome (Chr) 3 and of the homoeologous cattle and goat Chrs 11 with two DNA sequences: the beta lactoglobulin gene (LGB) and an immunoglobulin M heavy chain-like sequence (IGHML). The results are in agreement with the high degree of banding pattern similarity, previously reported, among cattle, sheep, and goat karyotypes. PMID- 8499655 TI - Mapping of multiple mouse loci related to the farnesyl pyrophosphate synthetase gene. AB - The prenyltransferases are a class of enzymes involved in the synthesis of sterol and nonsterol isoprene compounds. We report here the chromosomal mapping of nine loci in the mouse that hybridize to the cDNA for the enzyme farnesyl pyrophosphate synthetase (FPS), a prenyltransferase that catalyzes the synthesis of an intermediate common to both the sterol and nonsterol branches of the isoprene biosynthetic pathway. Mapping was performed with genomic DNA from a mouse-hamster somatic cell hybrid panel, and by linkage analysis with recombinant inbred strains and the progeny of an interspecific backcross. The mapped loci have been designated farnesyl pyrophosphate synthetase-like-1 (Fpsl-1) on mouse Chromosome (Chr) 3; Fpsl-2 on Chr 4; Fpsl-3, Fpsl-4, and Fpsl-5, dispersed on Chr 10; Fpsl-6 on Chr 12; Fpsl-7 on Chr 13; Fpsl-8 on Chr 17; and Fpsl-9 on Chr X. It is presently unclear which of these loci encode active prenyltransferases and which may correspond to pseudogenes. The strongly hybridizing loci provide convenient genetic markers for seven mouse chromosomes. PMID- 8499656 TI - Reassignment of the H-ras-1 gene to the Hbb-terminus region of mouse chromosome 7. PMID- 8499657 TI - Corrected centromere orientation for mouse chromosome 19 MIT markers. PMID- 8499658 TI - Molecular markers that define the distal ends of mouse autosomes 4, 13, and 19 and the sex chromosomes. PMID- 8499659 TI - Genetic mapping of the mouse gene encoding dipeptidyl aminopeptidase-like proteins. PMID- 8499660 TI - Ethylene glycol monomethyl ether (EGME) exposure of male mice produces a decrease in cell proliferation of preimplantation embryos. AB - In this study using an aggregation chimera assay we examined male mice exposed to a nonmutagenic reproductive toxicant, EGME, for the transmission of impaired viability to their progeny preimplantation embryos. Prior to their aggregation into pairs, one of the embryos was labeled with a viable dye fluorecein isothiocyanate (FITC) to determine the relative cellular contribution from each partner embryo when chimeras were dissociated 30 to 35 h later (2 to 3 cell cycles). Direct cell-cell contact of embryos derived from exposed males and embryos from control males creates a competitive situation that has been shown to confer a cell proliferation disadvantage to the embryo from an exposed parent. The cell proliferation disadvantage is expressed as a "proliferation ratio": number cells from an experimental embryo/total chimera cell number. Male mice were exposed to EGME by gavage for 5 days with 0, 50, 200, 750, or 1500 mg/kg and were serially mated with unexposed female mice for the next 7 weeks. Proliferation ratios were significantly decreased in the 50, 200, and 750 mg/kg dose groups at week 4, which corresponds to the pachytene spermatocyte stage of spermatogenesis. Proliferation ratios were also significantly decreased in the 1500 mg/kg group at week 5. Due to transient infertility in this dose group, there were not sufficient numbers of embryos to evaluate for week 4. These results indicate that male mice exposed to EGME transmitted adverse effects to their progeny embryos that were expressed as an embryonic cell proliferation disadvantage in the chimera assay. PMID- 8499661 TI - Embryonic losses after 10-week administration of cobalt to male mice. AB - Cobalt toxicity was evaluated in the dominant lethal assay (DLA) to determine whether the detrimental effects of cobalt on spermatozoa would have an impact on offspring. Male B6C3F1 mice were treated with cobaltous chloride (400 ppm Co) for 10 weeks and mated. Neither the stage nor rate of development in vitro of 2-cell embryos to blastocyst from cobalt-treated males was affected. There was an increase in preimplantation losses and a decrease in total and live births, but no change in postimplantation losses from litters at day 19 of gestation. Fertility of the males was maintained during the 10-week cobalt treatment period, decreased during the DLA, and recovered over the next 6 weeks. Sperm parameters at the end of DLA and the recovery period showed that cobalt decreased all parameters measured at 12 weeks, but these parameters, except concentration, recovered to control levels by 18 weeks. Tissue concentrations of cobalt measured by atomic absorption analysis were increased in liver, kidney, testis, and epididymis after 12 weeks of cobalt treatment. We conclude that cobalt affected preimplantation losses in the DLA by compromising the fertility of treated males. PMID- 8499662 TI - Drug intoxication during pregnancy: a study with central registries. AB - By linking two health registries, one on all infants born and one on hospital discharges, 424 infants were identified born after pregnancies when the mothers had been hospitalized for an intoxication, mainly with drugs. In 126 infants, exposure had occurred during the organ forming period, 99 of them because of suicidal or accidental overdosage of drugs; 70 of these were psychoactive drugs. None of the 70 infants had a congenital malformation, but the upper 95% confidence limit includes a 10% risk increase. An effect on low birth weight rate was seen only after drug complications following medical treatments during weeks 12 to 30. The study supports an earlier study from Hungary that reported that drug intoxication during pregnancy does not carry a substantial teratogenic risk. PMID- 8499663 TI - Acetazolamide with caffeine causes exencephaly in "resistant" SWV mice. AB - Pregnant SWV mice were treated on day 9 of gestation (PC) with 50 mg/kg of caffeine (CAFF), 200 mg/kg (LD) or 1000 mg/kg (HD) of acetazolamide (ACZM), or a combination of both agents, or on day 8 PC with both agents (ACZM + CAFF). Untreated (UNTD) and vehicle-treated (VEH) groups served as controls. The SWV strain is widely reported to be resistant to ACZM; it was resistant to ACZM or CAFF + ACZM when treated on day 9 of gestation, but a significant frequency of malformations, primarily exencephaly, was produced by ACZM + CAFF on day 8 PC. This study provides evidence that ACZM, coupled with a subteratogenic dose of caffeine can produce abnormalities in the "resistant" SWV mice, using the endpoint of exencephaly on day 8 of gestation. The mean number of ossified caudal vertebrae in day-9 treatments and ossified cervical vertebral centra in day-8 treatments were reduced. The frequency of ossification of the first cervical vertebra (C1) was reduced from 93% in UNTD to 39% in HD-ACZM day 9 PC and 69% in HD-ACZM + CAFF day 9 PC groups, and was also significantly reduced in the HD-ACZM + CAFF day-8 treated group. PMID- 8499664 TI - Angiotensin-converting enzyme inhibitors have no effect on ovulation and ovarian steroidogenesis in the perfused rat ovary. AB - The null hypothesis of this study was that the angiotensin-converting enzyme inhibitors, captopril and teprotide, would not reduce the number of ovulations in vivo and in vitro in the rat. Captopril (in three regimens) was administered continuously beginning prior to pregnant mare's serum gonadotropin and hCG to trigger ovulation. The number of in vivo ovulations were counted. Ovaries similarly primed with pregnant mare's serum gonadotropin were dissected and perfused in media with hCG and captopril (two regimens) or teprotide (one regimen). The number of in vitro ovulations and steroid production in the perfusions were evaluated. The results were evaluated by the Student's t test. Power calculations gave only a 20% chance of missing a 16% difference in ovulations or steroidogenesis. There was no inhibition of ovulation or change in steroid production in angiotensin-converting enzyme treated rats in vivo or in vitro. While angiotensin II has been shown to be an important mediator in the mechanism of ovulation, angiotensin-converting enzyme inhibition via captopril or teprotide does not result in angiotensin II antagonistic effects. Hypothetical mechanisms to explain this paradox are presented. PMID- 8499665 TI - Acute and permanent growth effects in the mouse uterus after neonatal treatment with estrogens. AB - Acute and late effects of neonatal estrogen treatment were studied in NMRI mice treated with diethylstilbestrol (DES) or estradiol-17 beta (E2) on days 1 to 5 after birth (estrogenized females). The uterine wet weight (UWW) response in 6 day-old females, after 5 daily treatments with DES, had a peak at a daily dose of 10(-2) micrograms DES and declined with higher doses. Females (26-day-old) treated with DES or E2 neonatally had a reduced UWW response to a challenge with DES; on a dose basis, DES was more effective neonatally than E2. A single injection with DES or E2 in the neonatal period stimulated mitotic activity in the uterine horn epithelium; the UWW response to a 24-h DES pulse increased from day 2 to 6 after birth, but the uterine epithelial mitotic rate response decreased. Epidermal growth factor (EGF) was a more potent stimulator of mitotic activity than DES or E2. DES inhibited mitotic activity in the uterine cervical epithelium; EGF protected from this DES effect. In adult estrogenized females, EGF-induced uterine stimulation of 3H-thymidine incorporation subsided more rapidly than in control females; uterine epithelium did not respond to EGF in vitro. Uterine stroma of adult estrogenized females is postulated to house a population of cells under nonovarian proliferation control while the uterine epithelium may be under influence of an ovary-dependent proliferation inhibiting factor that is gradually lost under culture conditions. PMID- 8499666 TI - Otis workshop on risk assessment. PMID- 8499667 TI - Principles of neurobehavioral teratology. PMID- 8499668 TI - Neurobehavioral teratology of isotretinoin. PMID- 8499670 TI - Arbitrary limits in scientific journals. PMID- 8499669 TI - Caffeine effects on meiotic maturation in hamster oocytes in vitro. PMID- 8499671 TI - Is statistical significance testing useful in interpreting data? AB - Although P values and statistical significance testing have become entrenched in the practice of biomedical research, their usefulness and drawbacks should be reconsidered, particularly in observational epidemiology. The central role for the null hypothesis, assuming an infinite number of replications, and the dichotomization of results as positive or negative are argued to be detrimental to the proper design and evaluation of research. As an alternative, confidence intervals for estimated parameters convey some information about random variation without several of these limitations. Elimination of statistical significance testing as a decision rule would encourage those who present and evaluate research to more comprehensively consider the methodologic features that may yield inaccurate results and shift the focus from the potential influence of random error to a broader consideration of possible reasons for erroneous results. PMID- 8499672 TI - Two cases of cervical pregnancy following in vitro fertilization and embryo transfer to the lower uterine cavity. PMID- 8499673 TI - Polycystic ovarian disease (PCOD)--pregnancy rate and outcome in in vitro fertilization. PMID- 8499674 TI - A comparative study of three ovulation induction protocols in polycystic ovarian disease patients in an in vitro fertilization/embryo transfer program. AB - PURPOSE: This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilization-embryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients were treated with clomiphene citrate (CC) plus human menopausal gonadotropin (hMG) (CC/hMG group), with purified menofollitropin (pFSH) plus hMG (pFSH/hMG group), and with pFSH/hMG plus gonadotropin releasing hormone analogue (GnRH-a) (analogue group). In the analogue group the suppression of luteinizing hormone (LH) with GnRH-a decreased the number of follicles < 12 mm on the day of human chorionic gonadotropin (hCG) administration and the number and percentage of immature oocytes retrieved and increased the percentage of mature oocytes retrieved. RESULTS: However, fertilization rates of oocytes, cleaved embryo rates, pregnancy rates following replacement, and pregnancy outcomes were not different. CONCLUSION: Although the suppression of the hypothalamic-pituitary ovarian axis with GnRH-a in PCOD patients improved follicular synchrony and oocyte maturity, none of the ovulation induction protocols was superior to the others with respect to pregnancy rates and pregnancy outcomes. PMID- 8499675 TI - Selection criteria for human embryo transfer: a comparison of pyruvate uptake and morphology. AB - PURPOSE: Pyruvate uptake is higher in human embryos developing to the blastocyst stage than those arresting at cleavage stages. To investigate whether pyruvate uptake provides an improved criterion for selecting embryos for transfer, we have measured uptakes by individual embryos noninvasively over 24-hr periods between the first day (day 1) postinsemination and embryo transfer on day 2 to 3 and correlated the levels with implantation and pregnancy outcome. RESULTS: The mean uptake was significantly lower for embryos that implanted than for those which failed to implant: 22.9 +/- 1.0 and 27.1 +/- 0.6 pmol/embryo/hr, respectively on day 2, and 22.4 +/- 1.5 and 26.9 +/- 0.8 pmol/embryo/hr, respectively, on day 3, but the wide range of uptakes by individual embryos was overlapping. CONCLUSION: We conclude that pyruvate uptake as the sole criterion for embryo selection cannot predict which embryos will implant after transfer. Assessment of embryos using morphological and developmental criteria, therefore, remains the most consistent, though inefficient, indicator of pregnancy potential. PMID- 8499676 TI - Transfer of embryos into the uterus: how much do technical factors affect pregnancy rates? AB - OBJECTIVE: Our objective was to identify the effect on outcome of (a) ultrasound assisted embryo transfer, (b) the use of different embryo transfer catheters, and (c) the length of time the patients remain in the supine position after embryo transfer. SETTING: The setting was a private fertility center. SUBJECTS: This was a prospective study of 178 in vitro fertilization and embryo transfers (IVF-ET) and 63 frozen embryo replacements (FER). RESULTS: The pregnancy rate was 28.7% following IVF-ET and 31.8% for FER. Ultrasound-assisted transfer did not affect the outcome (29 vs 30.3%). There was no difference in the performance of the Wallace and Frydman catheters with regard to outcome (30.3 vs 30.7%). Although there was an increase in pregnancy rate as the time interval in the supine position after ET increased, this needs a larger study. CONCLUSION: The parameter studies did not affect the outcome of IVF/ET or FER. Some factors encouraged us to recommend ultrasound-assisted transfer in some cases, and the use of a Frydman catheter for transfer and to encourage the supine position after transfer for longer periods. PMID- 8499678 TI - Comparison of cycle outcome for gamete intrafallopian transfer alone and in combination with intrauterine embryo transfer. AB - As an alternative to embryo cryopreservation, the efficacy of intrauterine transcervical transfer of a small number of embryos resulting from fertilization of supernumerary oocytes obtained during a GIFT cycle (GIFT-ET) was assessed in this investigation. Data from 72 consecutive GIFT (N = 27) and GIFT-ET (N = 45) cycles were retrospectively reviewed. Age and infertility diagnoses were similar among the two groups. Clinical pregnancy, ongoing pregnancy, and abortion rates per retrieval were not significantly different between the two groups. We conclude that GIFT-ET offers no advantage over GIFT alone and that cryopreservation of all supernumerary embryos with intrauterine transfer in subsequent cycles would maximize pregnancy rates from a single oocyte aspiration and GIFT procedure. PMID- 8499677 TI - Multiple attempts at embryo transfer: effect on pregnancy outcome in an in vitro fertilization and embryo transfer program. AB - PURPOSE: This study derives from the observation that a correlation exists between failed first attempts (FFA) at embryo transfer caused by one or more embryos remaining in the catheter and reduced pregnancy rates (20.3 vs 3.0%). The aim of this study was to examine the relationship between failed first attempts at transfer and contamination of the transfer set; the related aspects of cervix dilatation and late embryo transfer were also investigated. RESULTS: The following observations were made. Retention of embryos in the transfer sets significantly reduced the pregnancy rate (P = 0.015); catheters contaminated with blood and cervical mucus indirectly contributed to this effect by increasing the incidence of failed first transfer attempts. Even though cervical dilatations, if indicated by uterus sounding, were done 2 days before embryo transfer, no pregnancies were effected in these 18 cases (P = 0.0001). Late transfers of embryos, due to delayed fertilization or slow cleavage rates, yielded a pregnancy rate of 10.5%. CONCLUSION: The approach of immediately retransferring retained embryos does not solve the problem of reduced pregnancy rates in FFA cases. It is suggested that ET should be repeated 1 day later in FFA cases in an attempt to improve pregnancy rates. PMID- 8499679 TI - Evaluating the effect of age on endometrial responsiveness to hormone replacement therapy: a histologic ultrasonographic, and tissue receptor analysis. AB - OBJECTIVE: Our objective was to characterize the endometria of women of various ages placed on similar estrogen/progesterone replacement regimens prior to attempted donor embryo transfer using histologic, ultrasonographic, and steroid receptor markers in order to determine if advancing age has a detrimental effect on uterine responsiveness to pharmacologic sex steroid replacement therapy. STUDY DESIGN: This was a prospective open clinical trial. Functionally agonadal women aged 25 to 60 years receiving hormone replacement therapy underwent transvaginal ultrasound examination of the uterus followed by a timed endometrial biopsy on artificial cycle day 21. Endometrial histology and estrogen and progesterone receptors were analyzed from biopsy material. Subjects were assigned to three groups according to age: Group I, aged 25 to 39 years (n = 48); Group II, aged 40 to 49 years (n = 61); and Group III, aged 50 to 60 years (n = 13). Endometrial preparation was accomplished in all patients using the same sequential regimen consisting of oral micronized estradiol and intramuscular progesterone. RESULTS: Similar histologic, ultrasonographic, and steroid receptor characteristics were noted in all groups of patients regardless of age. A normal appearing midluteal secretory endometrium was demonstrated histologically in 85% of biopsies. However, 15% of biopsies exhibited intraluminal papillary excrescences within the glands and/or increase in the normal gland-to-stroma ratio. Three patients, one from each group, did not initially respond to replacement therapy and required further treatment. CONCLUSION: Functionally agonadal women exhibit normal or near normal endometrial responses to sex steroid replacement therapy designed to imitate the natural cycle through the sixth decade of life. PMID- 8499680 TI - Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism. AB - OBJECTIVE: The study investigated the neuropsychological status of women with induced hypoestrogenism. DESIGN: An ABA design was employed in which neuropsychological measures were repeated prior to, during, and after induction of hypoestrogenism with leuprolide acetate. SETTING: The study took place in a medical school affiliated in vitro fertilization clinic. INTERVENTIONS: Leuprolide acetate was administered to all subjects as part of in vitro fertilization. METHODS: Eighteen women receiving in vitro fertilization treatment underwent neuropsychological testing before, during, and after treatment with leuprolide acetate and gonadotrophins. The neuropsychological test battery was selected on the basis of previous patients' symptomatic complaints during periods of hypoestrogenism with leuprolide acetate. RESULTS: Depending upon the tests administered, some individuals showed significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances. However, in terms of group statistics, only two-point discrimination and delayed recall memory test performance proved significant. Not all measures were sensitive for the group, as many tests displayed a balance between individuals who showed practice effects and those who showed detrimental effects. CONCLUSIONS: For a substantial portion of individuals, hypoestrogenism can result in statistically significant or clinically noteworthy problems with memory, dexterity, and two-point discrimination. PMID- 8499681 TI - A self-programmable in vitro fertilization/gamete intrafallopian transfer patient database management system for MacIntosh computers. AB - PURPOSE: Our purpose was to develop a data processing system for a large in Vitro Fertilization/Gamete Intrafallopian Transfer (IVF/GIFT) practice which would (1) require minimal data entry time, (2) be easy to operate, (3) be simple to construct (no knowledge of procedural language or programming necessary), and (4) quickly collate and reduce data. RESULTS: A database management system was successfully constructed on an Apple MacIntosh computer which met the above criteria. The key elements of this database were its user-friendly features (MacIntosh-based system), adaptability (user was constantly able to update and revise the program as informational needs changed), and ability to perform complex searches and data analyses imposed by the individual operators. CONCLUSIONS: The software and hardware described in this report were found to be highly effective in meeting the ever-changing administrative and clinical needs of our IVF/GIFT program. PMID- 8499682 TI - Plasmanate as a medium supplement for in vitro fertilization. AB - PURPOSE: The purpose of this study was to evaluate the use of Plasmanate, a protein preparation containing human serum albumin and mixed globulins to autologous preovulatory maternal serum, as an in vitro fertilization (IVF) medium supplement. Plasmanate was used most often in cases involving unexplained infertility, sperm antibodies, and endometriosis or when serum was unavailable. RESULTS: In a retrospective analysis of 1019 consecutive IVF cycles, Plasmanate was used as the protein supplement to the fertilization medium in 28.6% and maternal serum was used in 71.4% of the attempts. Attempting to eliminate the effects of different medium lots and laboratory conditions, 450 matched patient cycles were compared using the two protein supplements. Finally, the effects of Plasmanate versus maternal serum were compared in prospective randomized trial on patients diagnosed with tubal infertility who were attempting IVF for the first time. The clinical pregnancy rate was 34% for the Plasmanate group versus 24% for those using maternal serum in the retrospective investigation. However, this trend was reversed in the prospective trial. CONCLUSION: Although further investigation is necessary, it appears that Plasmanate is an appropriate protein substitute in patient cases where serum is absent or unsuitable. PMID- 8499683 TI - Complications of transvaginal ultrasound-directed follicle aspiration: a review of 2670 consecutive procedures. AB - PURPOSE: Complications following transvaginal ultrasound-directed follicle aspiration are rare, making it difficult to assess their true incidence. During a 4-year prospective study the complications arising from a series of 2670 consecutive procedures were monitored. RESULTS: Vaginal hemorrhage occurred in 229 (8.6%) of the cases, with a significant loss (> 100 ml) in 22 (0.8%). Postoperative pelvic infection occurred in 18 (0.6%) of the cases. Hemorrhage from the ovary with hemoperitoneum formation was seen on two occasions and necessitated emergency laparotomy in one instance. A single case of pelvic haematoma formation from a punctured iliac vessel was also recorded; this settled without intervention. Of the 18 cases with infection, 9 were severe with pelvic abscess formation; microbiological examination of the pus from these cases suggests that the most common route of infection in such cases is probably by direct inoculation of vaginal organisms into the peritoneal cavity by the collecting needle. CONCLUSION: The low incidence of pelvic infection questions the value of using prophylactic antibiotics. No increased risk of infection was demonstrated in cases with preexisting peritoneal damage. PMID- 8499684 TI - The impact of D-Trp6 luteinizing hormone-releasing hormone (LH-RH) on carbohydrate metabolism. AB - BACKGROUND: The population exposed to repeated cycles of gonadotropin-releasing hormone analogue treatment before in vitro fertilization is growing rapidly. Sex steroids have been shown to induce changes in carbohydrate metabolism. In view of the effect of gonadotropin-releasing hormone analogues on sex steroid levels, it seems of interest to investigate carbohydrate metabolism following treatment with these compounds. PURPOSE: Our purpose was to assess possible changes in glucose tolerance following administration of the long-acting gonadotropin-releasing hormone and analogue, D-Trp6 LH-RH. DESIGN: A 3-hr oral glucose tolerance test with 100 g glucose was performed on all patients, before and after 6 weeks of treatment. RESULTS: No significant changes in either glucose tolerance or insulin levels following treatment with D-Trp6 LH-RH were demonstrated in the group of 25 women investigated. CONCLUSION: With respect to carbohydrate metabolism, D-Trp6 LH-RH may safely be administered to healthy women. Further studies are still required to assess the safety of this GnRH analogue when treating potentially diabetic and diabetic patients. PMID- 8499685 TI - A fast and efficient method for simultaneous X and Y in situ hybridization of human blastomeres. AB - PURPOSE: To use a 6-hr fluorescence in situ hybridization (FISH) procedure involving fluorochrome-labeled probes to determine the gender of blastomeres from arrested biopsied human embryos. RESULTS: Simultaneous detection of X and Y chromosomes was performed on 68 blastomeres with this technique. The FISH efficiency for gender determination was 95.5% (65/68). In addition, rehybridization with chromosome 8-specific probes was performed to determine the ploidy of blastomeres with more than two sex chromosomes. CONCLUSION: This technique offers an alternative to polymerase chain reaction for the preimplantation diagnosis of X-linked diseases and can also be used for ploidy assessment. PMID- 8499687 TI - The influence of osmolality on mouse two-cell development. PMID- 8499686 TI - Enhanced embryo development of rabbit oocytes fertilized in vitro with platelet activating factor (PAF)-treated spermatozoa. AB - PURPOSE: The purpose of this study was to determine the effects of PAF treatment of rabbit spermatozoa on in vitro fertilization and subsequent blastocyst formation. Rabbit spermatozoa were exposed to PAF (10(-7) M), lyso-PAF (10(-7) M), or HIS (385 mOsm/kg) for 15 min prior to insemination of ovulated oocytes. Fertilized oocytes were cultured to the hatched blastocyst stage. RESULTS: Fertilization rates with PAF were significantly higher than those of fresh (P < 0.001), lyso-PAF-treated (P < 0.01), HIS-treated (P < 0.05) spermatozoa. Two-cell embryos produced from oocytes inseminated with PAF-treated spermatozoa had significantly higher hatched blastocysts than oocytes inseminated with fresh (P < 0.01), lyso-PAF-treated (P < 0.05), or HIS-treated (P < 0.05) spermatozoa. CONCLUSION: We conclude that PAF treatment of spermatozoa increases fertilization rates and subsequent embryonic development. PMID- 8499688 TI - Subzonal insertion, a possible treatment for "defective oocytes". PMID- 8499689 TI - What school nurses really do--a study of school nurse utilization. AB - The functions of twelve school nurses in a large metropolitan school district were examined in relation to utilization of health services and student time lost from school using health problem categories. Findings suggest absentee data and utilization are valuable outcome measures supporting the importance of school health programming. PMID- 8499690 TI - Nutritional beliefs and practices of adolescent athletes. AB - Recent research suggests that the adolescent athlete is neither aware of nor prepared for the dual demands of sound nutritional practices in general and those demanded by his or her chosen sport activities. The dietary practices of young athletes fail to meet the energy requirements for high performance and may also threaten their well-being. To ascertain the dietary practices and beliefs of an adolescent athlete population, a survey was conducted among high school students who were engaged in at least one sport. The results show that students were consuming excessive fats and sugars, and failed to recognize nutritional practices critical to the demands of athletics. PMID- 8499691 TI - A partnership to save children's lives--the school nurse/Medic Alert kids program. AB - The Medic Alert Foundation, in a soon-to-be-launched national program, seeks to educate families about Medic Alert and how its emergency information service helps prevent emergencies from becoming tragedies. This report discusses the role the school nurse plays in determining which children are at risk, what needs to be done, and how Medic Alert can provide the needed protection. PMID- 8499692 TI - Youth coping with sexual orientation issues. AB - Youth who are struggling with the issue of sexual orientation often are aware of hostile attitudes within their families, schools, communities and among their peers, but are unable to find help. These young people are subject to humiliation, rejection, social isolation, and physical assaults, as well as life threatening STDs and HIV. Resultant emotional and behavioral symptoms may bring them to the attention of the school nurse, who is often perceived as the most accepting and accessible resource within the school setting. This article provides background information on homosexuality, suggestions for leadership in providing intervention, and resources to help the school nurse reach out to these unserved youth. PMID- 8499693 TI - Nursing practice management: Lili, aged 12, was diagnosed with rheumatic fever in the fourth grade. PMID- 8499694 TI - Computer use in the health office. PMID- 8499696 TI - Violence in the American family. PMID- 8499695 TI - Family patterns and primary prevention of family violence. AB - Although services for victims and treatment programs for batterers have priority in efforts to ameliorate family violence, primary prevention programs are also essential. The importance of primary prevention lies not only in the suffering which can avoided, but also because it is unlikely that sufficient treatment resources can be allocated to match the magnitude of the problem. The latter point is illustrated by the results of a study of nationally representative samples of 2,143 families (studied in 1975) and 6,002 families (studied in 1985). These studies show that a minimum of 16% of American couples experienced an assault during the year of the study, and that about 40% of these involved severely violent acts, such as kicking, biting, punching, choking, and attacks with weapons. These studies also identified risk factors that can serve as the focus for primary prevention, for example, early marriage, male dominance in the family and use of physical punishment. Educational and therapeutic efforts, and economic changes, which encourage equality and which teach the skills necessary for an equal relationship, can help prevent family violence. PMID- 8499697 TI - All in the family. PMID- 8499698 TI - Breaking the cycle of silence: a nurse's view. PMID- 8499699 TI - The health care provider's role in domestic violence. PMID- 8499700 TI - Should we admit immigrants with AIDS? PMID- 8499701 TI - Child abuse and neglect in New Jersey: an overview. PMID- 8499702 TI - Elder abuse. PMID- 8499703 TI - Spouse abuse--case studies. PMID- 8499704 TI - Child abuse--infant case studies. PMID- 8499705 TI - Elder abuse--case studies. PMID- 8499706 TI - Elder abuse--a case study. PMID- 8499707 TI - Implementation of PSDA: how are we doing? PMID- 8499708 TI - Oregon's plan for health care rationing. PMID- 8499709 TI - Abuse: breaking the cycle of violence: the victim's perspective. PMID- 8499710 TI - Casemix update. PMID- 8499711 TI - Specialisation and competency standards issues and developments. PMID- 8499712 TI - St George Hospital intensive care unit. PMID- 8499713 TI - Sharon McKinley, professor of nursing in critical care, University of Technology Sydney, Australia. PMID- 8499714 TI - One units experience in instigating change in an intensive therapy unit. AB - Critical care management and staffing levels are under constant review to ensure efficient staff utilisation and to apply structural efficiency principles. The staffing of our general intensive care unit was reviewed and reorganised creating what we believed to be an unsafe environment. As a group of Clinical Nurse Specialists (CNS) and critical care Registered Nurses (RN) we investigated the after hours management of the unit using a retrospective study and a current practice survey which we submitted to our administration. The data collected provided us with a strong case against reclassification of the Team Leader position and illustrates the need for clinicians to look objectively into current issues to support all discussions and concerns. PMID- 8499715 TI - Technology assessment applied: a comparison of ophthalmic diagnostic techniques to detect diabetic retinopathy among Aboriginal people in central Australia. AB - Diabetes mellitus is one of the non-communicable diseases that has accompanied Aboriginal exposure to Western life style. The prevalence of diabetes mellitus is higher in the Aboriginal population than in non-Aboriginal Australians (Holding, 1985) and many Aboriginals who have diabetes mellitus develop diabetic retinopathy. Early detection facilitates treatment and prevention of blindness, a sequela of diabetic retinopathy. This paper describes the use of technology assessment as a framework for comparing two diagnostic technologies, fundal camera and ophthalmoscope, for use with Aboriginal people in central Australia. PMID- 8499716 TI - HIV/AIDS and nursing: an ethical debate. AB - The purpose of this discussion is to provide the reader with a dual opportunity. It encompasses various ethical paradigms and concepts, thus broadening the horizons of those interested in the ethical processes. Furthermore, it deals with issues pertaining to AIDS/Human Immunodeficiency Virus (HIV) in an ethical framework. The discussion is designed not to provide answers, but rather to create a foundation for future postulation and discussion based on ethical issues arising from the complexities of AIDS/HIV. AIDS/HIV is discussed in three ways. The first perspective deals with the client's right to treatment, and the quality of treatment each should be able to expect. The second is the nurse's role in the care of clients with AIDS/HIV. It encompasses the right of refusal of a nurse to care for an HIV positive client if directed to do so. These arguments culminate in a final discussion which deals with discrimination; however, discrimination is presented in a predominantly ethical context. PMID- 8499717 TI - Will legislation make a difference? PMID- 8499718 TI - Reflections on a night shift in accident and emergency. PMID- 8499719 TI - Psychological and cultural mediator. PMID- 8499720 TI - Problem teeth. PMID- 8499721 TI - Student nurses' specialty choice: the influence of personality and education. AB - Before and after a nine week psychiatric-mental health (PMH) nursing program of their Diploma course, 51 second year student nurses completed a questionnaire on which they rated their interest in 14 nursing specialties. They also completed measures of personality and attitudes to psychiatric treatment. Factor analysis showed that students' initial specialty interests fell into three groups that were termed 'procedural', 'child/infant orientated', and 'action orientated'. After the PMH program, the popularity and interrelationships of specialty choice changed substantially. Community and psychiatric nursing became more popular, whereas some of the 'procedural' specialties became less so. Correlations showed that the more conservative nurses initially selected the more traditional nursing specialties, and there were statistically significant relationships between psychological defence style and specialty choice. These findings have implications for nursing specialty choice and recruitment. PMID- 8499723 TI - Rural nursing--at the crossroads? PMID- 8499722 TI - Documentation dilemma. PMID- 8499724 TI - No more 'only a nurse'. PMID- 8499725 TI - Nurses' liability in doctor-nurse relationships. AB - An exploration of the concepts of professional liability and its application to nursing, with particular emphasis on civil liability. It defines the concept of vicarious liability and explains its origins and purpose. The issue of personal liability and when this is applicable to the nurse is also addressed. A significant part of the discussion confronts the issue of liability in doctor nurse relationships in clinical practice. PMID- 8499726 TI - [Clinical and experimental studies on sanpin therapy for chronic cervical diseases]. AB - Chronic cervical diseases belong to the category of precancerous diseases whose treatment is important in preventing cervical cancer. 135 cases were treated with Sanpin preparations therapy after exclusion of heart, liver, kidney and cancerous diseases. After the treatment of 2-3 months, 133 cases were cured. Two cases have not finished their treatment courses and so have been excluded from the study. Among them, 110 have been followed up for 1 to 11 years. All of the patients with pretreatmental hypertrophic cervices had normal sizes after the treatment. The cure rate of cervical erosion was 83.81% and the cure rate of cervical neoplasms was 91.84%. The basic studies of toxicology, pharmacology, pharmacochemistry and genetic toxicology of the Sanpin pills and rods have been done. Results showed that this therapy was safe so long as its indications and contraindications were handled correctly and the drug was given routinely. This therapy is simple, economical, safe and effective. After short training, it can be applied in county and township hospitals. PMID- 8499727 TI - [Treatment of ABO blood type incompatibility caused early abortion with traditional Chinese medicine]. AB - This results of 30 cases with the history of abortion due to ABO blood type incompatibility treated with traditional Chinese medicine (TCM) were reported. The titer of serum IgG anti A/B antibody were determined in these patients. Antibody titer < or = 1:128 before pregnancy or < or = 1:64 after pregnancy were treated with TCM till delivery. 25 cases gave birth at full term, 5 cases were before term. Abortion, stillbirth or hemolytic newborn death were not found. The lower the maternal serum IgG anti A/B titer, the lower the incidence of hemolytic jaundice; while the earlier the treatment after pregnancy, the lower the occurrence of hemolytic jaundice also. PMID- 8499728 TI - [Clinical study of the treatment of endometriosis with promoting blood circulation and stasis removing method]. AB - The treatment of endometriosis by blood circulation promoting and stasis removing method is based on the experience carried in the "Ji Yin Gang Mu" and the fact that this disease belongs to the category of pelvic stagnant blood. The study group consisted of 53 women with endometriosis. They were manifested as dysmenorrhea, menoxenia, ovarian chocolate cysts and enlarged uterus. The control group consisted of ten women with normal regular menstrual cycle. This article deals with the method of using the hemodynamic index of uterus arterial blood flow. After treatment the blood flow amount of uterus arteries of 53 cases (study group) obviously decreased and their uterus arterial blood flow speed reduced markedly as compared with pretreatment status, (P < 0.001 and P < 0.01) respectively, while pre-treatment group was significantly higher than that of control group (P < 0.001). After medical treatment for 3.5 months, symptoms such as dysmenorrhea and menstrual disorder basically disappeared. 22 ovarian chocloate cysts became smaller and 16 disappeared. The pregnancy rate was 45%. The data of this study suggest that the mechanism of treatment of promoting blood circulation to remove stasis might be closely related to the regulation of physico-chemical characteristics of blood and the adjustment of the function of hemodynamics. PMID- 8499729 TI - [Clinical and experimental studies on royal made ping an dan in preventing motion sickness]. AB - Royal Made Ping An Dan (PAD) is a royal clandestine prescription of the Qing Dynasty Imperial hospital for emperors, empresses, ministers, imperial maids and eunuchs. Experimental study confirmed; (1) PAD had apparent peripheral effect in inhibiting vomiting and improving mental state (P < 0.05). (2) PAD possessed markedly sedative effect (P < 0.05). (3) PAD was able to strengthen the defence ability of gastric mucosa and decreased its damage induced by chemical irritation. (4) PAD could markedly relieve the spasm of intestinal smooth muscle in vitro. (5) PAD could inhibit the growth of common pathogenic bacteria in intestine and stomach such as B. coli and B. dysenteriae. (6) The study of toxicology suggested that PAD was safe for clinical use. The clinical results showed that PAD possessed the effect in preventing 274 persons on motion sickness. The total effective rate of PAD group was 83.9%, while that of Dramamine group was 60.8%. PAD revealed better effect than that of Dramamine. Therefore, the authors realize that PAD is a better preventive drug for motion sickness. PMID- 8499730 TI - [Clinical and experimental study on yifei jianshen mixture in preventing and treating infantile repetitive respiratory infection]. AB - In recent years, the incidence of infantile repetitive respiratory infection has been increasing. In order to prevent and treat this disease, the authors suggest that pathogenesis of this disease is mainly due to insufficiency of Lung, Spleen and Kidney, which caused the Qi Deficiency and Blood Stasis Syndrome, and thus formulated Yifei Jianshen Mixture (YFJSM). The clinical and experimental study was carried out accordingly. The results showed that this mixture could increase the immune function of human body, and improve microcirculation, and has the function of warming up Yang and replenishing Qi, nourishing blood and activating blood circulation and eventually of preventing and treating diseases. 305 cases were clinically observed, the total effective rate being 95.1%. The effect of treatment is obviously better than that of control using Yupingfeng powder (P < 0.01). The adrenocortical function, plasma nucleotide, immune function, microcirculation and others were the main technical indexes of models, which were nearly the same as clinical study. The toxicity test also showed that the YFJSM was non-toxic and had no side effect. The study proved that the mixture was highly effective and had no side effect. PMID- 8499731 TI - [Analysis of clinical effect and experimental study of 13 herbs anti-cough dyspnea decoction in the treatment of chronic bronchitis]. AB - In treating chronic bronchitis, the effect of 13 Herbs Anti-Cough-Dyspnea decoction was better than that of other traditional prescriptions such as Ephedria-almond decoction etc. The effective rate of this decoction in relieving cough, sputum, bronchial spasm and eliminating wheezing sound were 98.6%, 98.32%, 91.52% and 85.35% respectively. The total effective rate was 98%. The animal experiment revealed that the decoction was given to isolated trachea after medication for 30 min, the effective rate in easing bronchial spasm was 99.1 +/- 30.2%, which was two times than that of other prescriptions. PMID- 8499732 TI - [Research on immune complex in situ type glomerulonephritis treated with mai-luo tong in rabbits]. AB - Applying c-BSA to duplicate immune complex in situ type glomerulonephritis in rabbits and treating it with Blood Circulation Promoting and Stasis-Removing Drugs Mai-Luo-Tong, the results showed that proteinuria in the treated group was decreased significantly, as compared to the control group (P < 0.01). Under light and electron microscope, although glomerular basement membrane was irregularly thickened and subepithelial dense electron deposits were found in both groups, but histopathologic damage in the treated group less than that of control one. In the treated group micro-thrombus, erythrocytes and platelets aggregation, leukocytes impaction were not seen within glomerular capillary. Also in the treated group mesangial cell proliferation and granulocyte infiltration were decreased significantly (P < 0.01) and there was no apparent glomerular fibrosis in former group. PMID- 8499733 TI - [Effects of dachengqi decoction and rhubarb on cellular electrical activities in smooth muscle of the guinea-pig taenia coli]. AB - The effects of Dachengqi decoction (DCQ) and Rhubarb (Rb) on spontaneous cellular electrical activities of guinea-pig's taenia coli has been studied by intracellular microelectrode technique. DCQ and Rb could both improve depolarization of cell membrane, speed up the burst of slow wave potential (when drug concentration was 1%, P > 0.05; 10% or 20%, P < 0.05), which was dose dependent. At the same concentration, the effects of Rb were more significant than that of DCQ. These results suggested that DCQ and Rb enhanced directly the cellular electrical excitability so as to strengthen the contraction of colon, is one of the mechanisms of these drugs in cellular level on diarrhea action. The ionic basis of the effects might be that DCQ and Rb reduced the K+conductance of cell membrane in rest state. PMID- 8499734 TI - [Experimental study on kidney invigorating and lipid reducing decoction-yishen jiangzhi tang in the treatment of chronic renal failure]. AB - In exploring the effect of treatment of supporting the body resistance on chronic renal failure, a chronic renal failure model of rat was created by gastroperfusion of adenine and evaluation was made on the therapeutic effect of Kidney Invigorating and Lipid Reducing Decoction (KILRD). The mental state and body weight of the treated group have recovered well with polyuria and proteinurea improving, BUN and Creatinine decreasing, which appeared to be superior to the naturally recovered group. Renal pathological examination showed that: although the renal parenchymal damage was not reversed but its compensation was satisfactory with compensatory hypertrophy appearing in unaffected nephron. The dominant reaction in the affected area was polynucleomacrocytosis, foreign body granulamatosis, and interstitial lymphocytic infiltration, the fibrosis was inevident, while the above-mentioned condition in the naturally recovered group was relatively more serious, with fibrosis being observed. It was indicated that KILRD could increase the compensatory capacity and immunity, promote protein synthetization and improve renal function. The study on KILRD proved to be a significant conservative medical treatment for chronic renal failure. PMID- 8499735 TI - [Progress on combined traditional and Western medicine therapy in the treatment of medium and advance stage of esophago-cardial cancer]. PMID- 8499736 TI - [New aspects in the use of i.v. immunoglobulins. Workshop. Travemunde, 10-12 September 1992. Proceedings]. PMID- 8499737 TI - [High-dose immunoglobulin therapy of hyperbilirubinemia in rhesus incompatibility]. AB - We conducted a multicenter controlled trial to test the hypothesis that high intravenous doses of immunoglobulin (HDivIg) can modulate the bilirubin production and reduce the frequency of exchange transfusions in newborn infants with rhesus incompatibility. Thirty-four patients with rhesus incompatibility proven by positive direct antiglobulin test (Coombs test) were randomly assigned to conventional treatment including phototherapy, with or without additional HDivIg at 500 mg/kg given over 2 h, as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polacek by more than 2 mg/dl. The results in 32 infants were analyzed. In the HdivIg-treated group, 2 of 16 (12.5%) children required exchange transfusions, whereas it became necessary in 11 of 16 (69%) in the control group (p < 0.005). Bilirubin levels in the HDivIg-treated group were lower despite a reduced frequency of exchange transfusions. We conclude that HDivIg by a yet unknown mechanism reduces bilirubin serum levels in children with rhesus incompatibility and the need for exchange transfusions. PMID- 8499738 TI - [High-dose immunoglobulin therapy of rheumatoid arthritis]. AB - Eight patients suffering from severe rheumatoid arthritis were treated with high dose human immunoglobulin. Doses of 500 mg/kg were administered intravenously in the morning on 4 consecutive days. Improvement of arthritic symptoms was indicated by a significant decrease of the Ritchie index, the number of swollen joints, and the duration of morning stiffness as well as an increase of grip strength. The improvement lasted up to 4 months. In 2 patients the disease activity increased again after 4 weeks. Investigations of laboratory parameters demonstrated a significant reduction of the acute-phase response. Parallel investigations of immunological parameters revealed a decrease of Il-6 levels in the sera. Therefore, we suggest a decreased activation status of the monocyte macrophage system and T cells as a possible mode of action of high-dose immunoglobulin therapy in rheumatoid arthritis. PMID- 8499739 TI - [Use of intravenous immunoglobulins for immunomodulating therapy of inflammatory rheumatic diseases]. AB - The use of immunosuppressive and long-acting antirheumatic drugs in the treatment of rheumatic diseases is often limited by their side effects. Therefore, it is urgent to search for drugs which are better tolerated and which are at least as effective. Several studies have been performed using intravenously administered immunoglobulins in rheumatoid arthritis patients and in small groups of patients suffering from other connective tissue diseases. The results demonstrate a rapid onset of clinical improvement in patients who respond to this treatment. The tolerance has been excellent so far. This therapy is immunomodulating, since it induces changes in B- and T-lymphocyte function, especially in immunoregulatory T cell subpopulations. Future work should focus on the establishment of treatment schedules and on the definition of patient subgroups which might benefit most from intravenous immunoglobulin therapy. PMID- 8499740 TI - [Immunomodulating therapy of systemic juvenile rheumatoid arthritis: administration of high-dose intravenous gamma globulin]. AB - Two children of 9 and 10 years suffering from severe systemic juvenile rheumatoid arthritis were treated intravenously with high-dose human immunoglobulin. Treatment was performed every 4 weeks for 7 and 18 months, respectively. Improvement of arthritic symptoms was demonstrable by significant decreases of Ritchie index and number of swollen joints and the disappearance of heated joints in one patient. The other patient was free of arthritic symptoms since the introduction of immunoglobulin therapy. Clinical symptoms of systemic illness were markedly improved and no relapse was seen. Laboratory parameters also improved, including erythrocyte sedimentation rate, C-reactive protein, hemoglobin, and serum iron levels. Parallel investigations of immunological parameters revealed a decrease of serum Il-1 beta and Il-6 levels and a diminished in vitro production of Il-1 beta, Il-6, and tumor necrosis factor alpha. Therefore, we suggest a decreased activation status of the monocyte macrophage system as one possible mode of action. PMID- 8499741 TI - [Modification of systemic signs and elastase in neutrophilic granulocytes in inflammatory rheumatic diseases in childhood by immunoglobulin therapy]. AB - Eight children suffering from various rheumatic diseases were treated with high dose intravenously administered immunoglobulins. Signs of the disease were well controlled by this treatment. In all cases the levels of neutrophilic granulocyte elastase decreased during treatment, while there was no improvement of joint disease. PMID- 8499742 TI - [Intravenous administration of immunoglobulins in systemic lupus erythematosus: review of the literature and initial clinical experiences]. AB - About 10 years ago, the first reports about the successful treatment of autoimmune thrombocytopenia with high-dose intravenously administered immunoglobulins (ivIg) were published. Since this time ivIg have been tried for treating almost any autoimmune disease. However, reports about this treatment modality are only anecdotal. So far, ivIg are a widely used and accepted treatment only for autoimmune thrombocytopenia and Kawasaki disease. During the last years many groups tried to gain a better understanding of the mechanisms by which ivIg exert their effects in autoimmune diseases. In systemic lupus erythematosus (SLE) only case reports are available which describe encouraging positive effects of ivIg especially in patients with cytopenia and vasculitis. However in some cases a serious impairment of renal function after ivIg therapy has been reported. This was seen mainly in SLE patients who already had renal involvement before ivIg therapy was started. Therefore, extreme caution should be exercised in these patients until we know more about the pathophysiology of this side effect. We have treated 6 SLE patients with high-dose ivIg (400 mg/kg, 5 days). One patient had a remission for 6 months, another patient for 36 months; in 2 patients with preexisting reduced renal function we observed two acute renal failures and in 1 patient a decrease of the renal function 1 month after ivIg treatment. These preliminary data demonstrate the necessity of controlled clinical trials to prove the effectiveness, to define indications, to find the optimal dosage, and to study the possible mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499743 TI - [New therapeutic aspects in Kawasaki syndrome and personal experiences]. AB - Kawasaki disease is an inflammatory disease of unknown etiology. The prognosis depends mainly on cardiac, mostly coronary involvement which can be significantly reduced with the use of immunoglobulins. The current recommended therapy consists of a single dose of immunoglobulins (2 g/kg i.v.) combined with acetylsalicylic acid. During 1984-1992 we diagnosed Kawasaki disease in 35 patients. Three of them not treated with immunoglobulins developed coronary aneurysms. PMID- 8499744 TI - [Intravenous immunoglobulins in bronchial asthma: a therapeutic alternative?]. AB - Treatment of severe bronchial asthma usually requires the use of steroids. Given the known side effects of steroid treatment, potential alternative therapeutical strategies are currently evaluated; among others, intravenously administered immunoglobulins (ivIg) may be considered. In one study of 5 children with bronchial asthma and IgG subclass deficiency, an improvement of asthma was demonstrated in 4 out of the 5 patients under ivIg treatment over several months. In another study on ivIg treatment in 8 immunocompetent children with steroid dependent asthma, there also was an improvement of asthma, leading to a reduction in the required steroid dose; furthermore, there was a diminution in skin prick test reactivity. At present, only speculations can be made about the possible mechanisms of action. PMID- 8499745 TI - [High-dose immunoglobulin treatment of epilepsy in children]. AB - High-dose, intravenously administered immunoglobulins have been successfully applied to a few cases of childhood epilepsy and led to a reduction of the seizure frequency in a number of studies. In the present study 4 patients with myoclonic-astatic petit mal or myoclonic absence were treated with intravenously administered immunoglobulins (400 mg/kg for 5 days). Deterioration occurred in 1 patient, 1 patient showed no effect, and 2 patients showed a partial and transient response. Theoretically, the rationale for immunoglobulin therapy in epilepsy is based on the assumption of autoimmune mechanisms as being the underlying pathogenesis. However, a review of the literature showed that the few studies available differ in the forms of epilepsy treated and the effects obtained. No study correlated the effects of immunoglobulin administration with a presumptive autoimmune disorder. As a result, high-dose intravenous immunoglobulin treatment of childhood epilepsy remains empirical and the group of patients who might benefit from such a treatment continues to be poorly defined. PMID- 8499746 TI - [Detection of endotoxin in plasma: specificity and value for development and prognosis of infection]. AB - A number of problems may be involved in the detection of endotoxin in plasma of patients using LAL (Limulus amebocyte lysate). When collecting blood or processing samples, contamination with endotoxin or its adsorption to material must be avoided. In our laboratory a kinetic LAL microtiter assay was developed that takes into account plasma-related interferences with the LAL endotoxin reaction by performing an internal standardization in each sample. Negative results do not absolutely exclude the involvement of endotoxins in the underlying disease. High levels of endotoxins do not necessarily reflect the severeness of the clinical status of the patient. Due to nonendotoxin-specific reactions with some complete lysates, false-positive levels may result, e.g., following immunoglobulin therapy. In spite of these limitations, the LAL test remains a valuable tool in the evaluation of gram-negative infections. PMID- 8499747 TI - [Continuous measurement of peripheral oxygen availability in skeletal muscle of patients with infection]. AB - In patients with sepsis, a pathologic oxygen uptake supply dependence due to an oxygen extraction defect was suggested to result in tissue hypoxia--a hypothesis which is discussed controversially. In order to determine more directly whether the oxygen transport to tissue was reduced in patients with sepsis, the distribution of skeletal muscle pO2 was measured intermittently by polarographic needle electrodes in 28 patients with sepsis for 7 days. Comparison of intermittent with continuous measurements by pO2 catheters showed a close linear relation (r = 0.88; p < 0.001) and acceptable agreement. Therefore, continuous measurement of skeletal muscle pO2 by pO2 catheters can be used as an estimate of mean skeletal muscle pO2. Neither by intermittent nor by continuous measurements, skeletal muscle hypoxia was detected in patients with sepsis. In contrast, the skeletal muscle pO2 was statistically significantly higher on days with septic state (44.1 +/- 10.3 mm Hg) than on days with intermediate (30.1 +/- 8 mm Hg) and nonseptic (26.8 +/- 5.1 mm Hg) states. From our data we infer that the hypothesis of tissue hypoxia in sepsis must be questioned at least for the skeletal muscle. The increase of skeletal muscle pO2 in sepsis, however, suggested that oxygen utilization within skeletal muscle decreased the more severe the stage of sepsis was. A decreased oxygen utilization within tissue, which may result from a 'downregulation' of oxygen-dependent metabolic pathways, might account for a decreased oxygen extraction of peripheral tissue in sepsis. PMID- 8499748 TI - [Preventive and therapeutic use of intravenous administration of immunoglobulins in intensive care patients in pediatrics]. AB - The intravenous infusion of immunoglobulin preparations (ivIg) still is no established mode of therapy for neonatal septicemia or for the prevention of nosocomial infections in premature infants. Some recent studies show a decrease in nosocomial infections by ivIg infusions. However, a significant reduction in infections by any specific pathogen has not been demonstrated; the specific antibody content of the ivIg preparations in relation to these pathogens has not been examined. No statistical differences were found regarding duration of hospitalization, morbidity, or mortality of premature infants. ivIg seem to have positive effects on neonatal isoimmune thrombocytopenia or on thrombocytopenia caused by maternal immunothrombocytopenic purpura. There is also evidence that ivIg could have a positive effect on the course of Guillain-Barre syndrome, although this has not been proven for children. PMID- 8499749 TI - [Early immunoglobulin therapy in high risk patients for infection after heart surgery]. AB - The efficacy of early supplemental intravenous immunoglobulin G (ivIgG) treatment was investigated in 41 patients at risk for sepsis following cardiac surgery (APACHE II score > or = 19 on the 1st postoperative day). The ivIgG preparation (Psomaglobin N) was chosen because of its reported high antibody titers and effectiveness in animal models against gram-positive microorganisms, preponderant as infective agents after heart surgery. The control group consisted of a historical cohort of 42 cardiac surgical patients of comparable pretreatment disease and sepsis severity. Following ivIgG therapy on the 1st and 2nd days after surgery, we found a marked improvement in disease severity (fall in APACHE II scores) in contrast to the control patients, especially evident in the high risk group of patients with an APACHE II score > or = 24 on the 1st postoperative day (n = 26). In this group, ivIgG therapy led to higher (p < 0.05) response rates defined as a score decrease > or = 7 within 4 days (ivIgG-treated patients 54%, controls 19%), and a reduction in mortality (ivIgG-treated patients 46%, controls 76%; p = 0.08). Given the good comparability of the study groups, the results of this trial indicate, despite its nonrandomized design, that early supplemental ivIgG treatment seems to decrease disease severity and probably also improve the prognosis in APACHE II score identified high-risk patients after cardiac surgery. PMID- 8499750 TI - [Passive immunotherapy for treatment of endobronchitis in cystic fibrosis]. AB - Chronic endobronchial infection with Pseudomonas aeruginosa is a major clinical problem in cystic fibrosis, a genetic disorder of epithelial ion transport and mucus secretion. Functional defects in the opsonic antibody response to critical surface antigens of P. aeruginosa, including lipopolysaccharide and mucoid exopolysaccharide (alginate), have been implicated in the initial colonization and/or persistence of infection of the respiratory tract of cystic fibrosis patients with this bacterium. These defects are correctable in vitro with functional opsonic antibodies against P. aeruginosa present in intravenously administered immunoglobulins (ivIg). Moreover, functional opsonic polyclonal and monoclonal antibodies against P. aeruginosa are protective in animal models of chronic pseudomonal endobronchitis. Two pilot studies on passive immunotherapy with ivIg--one with standard ivIg and one with hyperimmune globulin enriched with anti-Pseudomonas lipopolysaccharide antibodies (Psomaglobin N)--have demonstrated safety and short-term efficacy in terms of improved pulmonary function. Multicenter placebo-controlled trials of passive immunotherapy with conventional ivIg and hyperimmune globulin enriched with antibodies against P. aeruginosa alginate are planned in the United States. PMID- 8499751 TI - [Serum IgG concentrations and antibody titer of burn patients after preventive intravenous IgG substitution with a Pseudomonas immunoglobulin]. AB - In a randomized clinical trial 30 patients with burn injury received supportive therapy with a Pseudomonas hyperimmunoglobulin (Psomaglobin N). The control group received no additional therapy. The patients of both groups were between 15 and 60 years of age and had a full-thickness burn of 30-70% of the body surface area with inhalational trauma being optional. The whole trauma was classified and scored with the 'Abbreviated Burn Severity Index' (which allows another extra score point for inhalational trauma). Both groups underwent the same intensive care unit treatment with preference to early wound excision and wound grafting following functional aspects of reconstructive surgery. Bacteriological monitoring was performed on suspicion of wound infection and bacteremia by taking wound swabs and blood cultures. The supportive treatment group received a total of 250 mg/kg hyperimmunoglobulin on days 3, 5, 7, 10, and 13. Of 30 patients in the control group 16 had an additional inhalation trauma, and 8 of those (50%) died (only 1 of 14 patients without inhalation trauma died). In the group receiving supportive treatment, 23 out of 30 patients had an inhalation trauma, and 8 of those (35%) died (1 of 7 patients without inhalation trauma). In both groups with inhalation injury, the patients were at risk of developing bacteremia: 13 of 23 of the immunoglobulin-treated patients and 12 of 16 patients of the control group. Bacteremic controls died at a lower score than bacteremic immunoglobulin-treated patients (8.6 vs. 10.3 points).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499752 TI - [Laboratory diagnosis of immune deficiency]. AB - Highly specialized, state-of-the-art diagnostic tests are available for identifying congenital and acquired immune defects. These methods should only be resorted to when less complicated means have created suspicion of an immune defect. The case history, including the family history, represents the core of the diagnostic procedure. Initially, only simple clinical investigations are indicated. These should enable the physician to exclude or delimit a defect in the immune system which then can be defined more closely by specific tests. Screening includes clinical chemistry (erythrocyte sedimentation rate, total serum protein, serum electrophoresis, C-reactive protein, blood count including differential blood count, ferritin, urine analysis, and a quantitative assay of the immunoglobulins A, G and M), bacteriological, serological, and radiological investigations, and finally skin tests with recall antigens. Thereby, it is usually possible to reliably detect primary B cell defects with humoral antibody deficiency syndromes. Lymphocyte subset counts, immunoelectrophoresis, and bone marrow biopsy are necessary for the differential diagnosis, or for the confirmation, of malignant lymphatic proliferation, especially in adults. IgG subclass defects as well as granulocyte dysfunction and complement defects must be excluded in patients who are susceptible to bacterial infection despite normal immunoglobulin concentrations. In suspected cases of primary or secondary (HIV, cytomegalovirus, Epstein-Barr virus) T cell defects, lymphocyte subset counts and, where applicable, T cell function tests are indicated. The majority of secondary immunodeficiency syndromes, in which the primary disease is known, do not currently require specialized diagnosis. Nevertheless, monitoring of the lymphocyte subsets in HIV-positive patients has already become standard practice in health care (for evaluating the prognosis and deciding on the therapy). PMID- 8499753 TI - [Early detection of patients at risk for infection after heart surgery]. AB - Since sepsis is a major cause of mortality after cardiac surgery, early identification of the patients at risk of developing septic complications is of considerable importance. In the present study on 110 patients after elective heart surgery, we, therefore, examined scoring systems as well as various single parameters with regard to an early prediction of septic complications. In a first step, the Elebute score definition for postoperative sepsis in general surgery patients (score > or = 12) could be confirmed for cardiac surgery patients as well. Septic complications, defined as an Elebute score > or = 12 on > or = 2 days, occurred in 16 patients and were associated with a significantly worse prognosis than in non-septic patients (mortality 69 vs. 1%). Consequently, other more practicable parameters were investigated: five additional scores (APACHE II, Goris, HIS, SAPS, SSS) were comparable and superior to plasma levels of elastase and neopterin, haemodynamic data, and clinical parameters in predicting septic complications as early as by the 1st postoperative day. For reasons of practicability and availability, the APACHE II score (predictive values: positive 86%, negative 96%, Youden index 0.73; diagnostic cut off point: > or = 19 on the 1st postoperative day) seemed to be best suited. Therefore, this was further investigated within a consecutive prospective study (independent group of 106 patients) which confirmed an APACHE II score > or = 19 as discriminating criterion (mortality 36 vs 0%). Thus, the APACHE II score may be useful for prospective screening, with the intention to treat, of patients after cardiac surgery who are at risk of postoperative septic complications. PMID- 8499754 TI - [Immunoglobulin therapy in patients after autologous and allogeneic bone marrow transplantation]. AB - Following bone marrow transplantation many patients are suffering from an impaired immunoglobulin production. Treatment with intravenous immunoglobulin has significantly reduced the incidence of infections as well as severe graft-versus host disease during the early posttransplant period. However, no complete protection of the patients has been achieved. According to our own observations, especially patients with a decreased production of IgM antibodies seem to have an increased risk of cytomegalovirus-induced pneumonitis. During the late posttransplant period, patients with IgG subclass deficiency are at risk of acquiring gram-positive infections. However, randomized studies investigating the effect of immunoglobulin treatment during the late posttransplant phase have not yet been conducted. PMID- 8499755 TI - [Immunoglobulin substitution in malignant lymphoma]. AB - Substitution with intravenously administered immunoglobulin seems to be indicated in lymphoma patients with acquired immunoglobulin deficiency, i.e., primarily patients with chronic lymphocytic leukemia and multiple myeloma. Infectious complications, mainly of the upper airways, are a major cause of morbidity and mortality in these patients. The immunoglobulin levels are correlated with stage of the disease, frequency of infections, and patient survival. Besides immunoglobulin deficiency, there are less well characterized defects of cellular immunity. Three prospective studies evaluating the effectiveness of immunoglobulin substitution in patients with chronic lymphocytic leukemia and myeloma have been published. A dose of 400 mg/kg or 10 g of immunoglobulin was administered intravenously every 3 or 4 weeks. A reduction of bacterial infections, but not of deaths due to infectious complications, was observed. The treatment was usually well tolerated with few side effects. However, to date it has not been established which patient subgroups really benefit from immunoglobulin therapy in terms of improvement of quality of life. Thus a general recommendation of immunoglobulin therapy in chronic lymphocytic leukemia and multiple myeloma can at present not be made. PMID- 8499756 TI - [Mechanisms of immune modulation in immune thrombocytopenia]. AB - Since Imbach's publication in 1981 on the effect of high-dose intravenous immunoglobulins in idiopathic thrombocytopenia of childhood, many studies have been performed in order to elucidate their mechanism of action. In this review, the author tries to illustrate the mechanisms which are currently discussed and which are sufficiently supported by experimental data. PMID- 8499757 TI - [Therapy of autoimmune thrombocytopenia in adults]. AB - Autoimmune thrombocytopenic purpura (AITP) is an immune disease characterized by the destruction of antibody-coated platelets in the reticuloendothelial system. It is a relatively common hematologic problem. The diagnosis is established by exclusion of differential diagnoses. Clinically, an acute and a chronic form of AITP can be distinguished. We discuss the different treatment modalities based upon data provided by various studies on AITP. If treatment with glucocorticoids or with immunoglobulins fails, or after unsuccessful splenectomy, then experimental treatment strategies may have to be used. Some of these treatments are described with reference to their mode of action and therapeutic benefit. PMID- 8499758 TI - [High-dose immunoglobulin therapy of aplastic syndrome]. AB - Idiopathic pure red-cell aplasia was successfully treated by high-dose intravenous immunoglobulin infusions (HDivIg) in 2 patients; 1 of these patients was refractory to other immunosuppressive drugs. We have observed responses to this therapy also in 3 of 5 patients--without pretreatment--with severe aplastic anemia. HDivIg treatment had no significant side effects; patients with aplastic syndromes could be treated as outpatients. Patients responding to HDivIg demonstrated different response patterns to ciclosporin A. Sequential treatment of aplastic syndromes with high-dose prednisone, HDivIg and ciclosporin A was effective in 6 of 7 patients. The results in this pilot study are comparable to those with other immunosuppressive strategies in patients with severe aplastic anemia who lack a bone marrow donor. Optimal dosage, sequence, and duration of this treatment modality remain to be defined. PMID- 8499759 TI - Radioiodine turnover studies as a means to predict stable intrathyroidal iodine stores and comments upon its use in the diagnosis and treatment of hyperthyroidism. AB - Stable intrathyroidal iodine pool (ITI) is known to affect both diagnosis and treatment of hyperthyroidism. Very few laboratories have facilities to measure ITI. In our department x-ray fluorescence was routinely used for more than 15 years. We report here that it is possible to predict the ITI by means of classic 131I turnover studies and at least distinguish hyperthyroid patients with a small ITI pool ("small pool" patients) from those with a large ITI. It could be shown from a retrospective study (selected hyperthyroid patients, n = 118) that (1) in our area the small pool patients represent the majority as opposed to the situation in the United States, (2) that there was a highly significant negative correlation (p < 0.001) between the PB 131I at 24 h and ITI, and (3) that the non small pool patients were more resistant to treatment than the others. In a prospective study of 91 consecutive patients with a thyroid problem, it was be shown that in the euthyroid group no correlation could be found between ITI on the one hand and 131I uptake and PB 131I at 24 h or urinary iodine on the other. In the hyperthyroid patients a strong negative correlation was again found between ITI and PB 131I (p < 0.001), stronger than with 131I uptake p = 0.093). No correlation existed with urinary iodine. In a second prospective study of hyperthyroid patients (n = 56), it was confirmed that measuring the PB 131I could classify hyperthyroid patients into non-small pool and small pool subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499760 TI - Prevalence of fractures in postmenopausal women with thyroid disease. AB - We interviewed 300 white postmenopausal women (160 with thyroid disease, 140 without thyroid disease) to investigate whether having thyroid disease or taking thyroid hormone increased the prevalence of having a hip, vertebral, or forearm fracture. Thirty-seven (23%) women with thyroid disease and 45 (32%) women without thyroid disease had had a fracture, and there were no significant differences between these groups in the number or type of fractures. Dose of thyroid hormone and duration of therapy or disease did not affect fracture occurrence in women with thyroid disease. Women with a history of hyperthyroidism (9 of 32) or thyroid cancer (2 of 11) appeared to have their first fracture earlier (p < 0.01) than women without thyroid disease. In summary, women taking thyroid hormone for a variety of thyroid disorders do not appear to have an enhanced prevalence of a hip, vertebral, or forearm fractures, but women with a history of hyperthyroidism may have a propensity for their fractures to occur earlier in life. PMID- 8499761 TI - Distinguished service award. PMID- 8499762 TI - Colonic excretion of iodide in normal human subjects. AB - Patterns of fecal radioiodine excretion were studied in seven normal young men with intact, unblocked thyroid glands, who received repeated oral daily doses of [125I]iodide in an attempt to achieve isotopic equilibrium. Fecal radioactivity was assumed to have originated either in the circulating inorganic radioiodine (radioiodide) compartment or in the circulating hormonal protein-bound iodine (PBI) compartment. Activity in the PBI compartment was measured directly in serum samples from which radioiodide had been removed by dialysis or resin treatment. Activity in the radioiodide compartment was measured by the difference between total and hormonal radioiodine, and also as a projection from the rate of urinary excretion of radioiodine. These compartments were fitted to the observed sequential fecal radioiodine data in each subject to identify the origins of the fecal radioactivity, using the SAAM modeling program. The fraction of fecal radioactivity attributable to iodide was 0.55 +/- 0.35 (mean +/- SD) (geometric mean 0.44, range 0.25-0.96). In all cases, at least some contribution from the iodide compartment was required for model fit to the observed pattern of fecal radioiodine excretion. These data demonstrate that, despite long-existing opinion to the contrary, iodide is an important component of intestinal iodine excretion in humans. This finding explains the presence of colonic activity in postradioiodide images of athyreotic patients. PMID- 8499763 TI - Role of subunit sialic acid in hepatic binding, plasma survival rate, and in vivo thyrotropic activity of human chorionic gonadotropin. AB - Previous studies have shown that desialylation of human chorionic gonadotropin (hCG) results in a sharp enhancement of its affinity for thyroid thyroid stimulating hormone (TSH) receptors, transforming it from a weak to a potent antagonist of adenylate cyclase activity in vitro. Because most of the information on the structure-function relation of hCG as a thyroid stimulator has been derived from in vitro experiments, the present studies were undertaken to assess the role of its sialic acid residues in the expression of its thyrotropic activity in vivo. hCG and its various desialylated forms, viz., intact-alpha asialo-beta, asialo-alpha-intact-beta, and asialo-hCG (ashCG), were initially characterized in terms of their immunoreactivities and receptor-binding abilities as assessed in the rat testis assay. In neither assay did hCG or its variants exhibit a major discordance in activity. In the mouse bioassay, intact hCG (150 micrograms) proved to be a thyroid stimulator of considerable potency, exceeding the response induced by 0.2 mIU bovine TSH (bTSH), as measured by 125I release into the blood after 2- and 8-h intervals. Remarkably, both asialo-alpha-intact beta and ashCG significantly stimulated the mouse thyroid in this assay, though to a lesser degree than hCG itself. However, in the same assay intact-alpha asialo-beta was inactive. Studies of the survival of hCG and its variants in the circulation of the mouse, as assessed by radioimmunoassay (RIA) in multiple serum samples drawn over 30 min, showed hCG to have a long half-life, whereas ashCG was cleared very rapidly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499764 TI - Antithyroid and goitrogenic effects of coal-water extracts from iodine-sufficient goiter areas. AB - Goiter in iodine-sufficient areas has been linked to water-borne goitrogens in watersheds and aquifers rich in coal and shale. In the present study, the potential antithyroid and goitrogenic effects of coal-water extracts (CWE) were investigated in vivo in rats after chronic and acute oral administration of CWE, and in vitro by a thyroid peroxidase (TPO) enzyme system. CWE was prepared by continuous extraction of ground (40 mesh) Appalachian coal with goitrogen-free water (GFW). Female Buffalo rats fed on Purina iodine-rich diet (12 micrograms I /day/rat), were given ad lib CWE (50 mg/ml; approximately 20 mL/day/rat) or GFW (controls) for 2 months. At the end of the experiment, 125I 1 microCi, was injected i.p. and 4 h later the thyroid glands were removed, weighed, and analyzed histologically and for total 125I and 125I-labeled compounds. Rats on CWE had larger thyroid glands [7.2 +/- 0.3 mg/100 g (mean +/- SE) vs 5.0 +/- 0.5 controls; p < 0.005] with distinct histological changes of smaller thyroid follicles, some with columnar epithelium, and with more dense colloid than in controls, and had significant inhibition of the coupling mechanism for production of thyroid hormones [125MIT + DIT/125T3 + T4: 5.1 +/- 0.2 vs 3.9 +/- 0.1 controls, p < 0.005; and 125T3 + T4 (%): 10.6 +/- 0.3 vs 12.6 +/- 0.4 controls, p < 0.005]. Female Sprague-Dawley rats under the same conditions as Buffalo rats were given acutely by GI tube 2 mL of CWE (5 g/mL) or GFW (controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499765 TI - Endemic cretinism: toward a unifying hypothesis. AB - Based on our data, the clinical picture of endemic cretinism results from the product of two pathophysiological events. Both events share a common feature, namely iodine deficiency, but act at different points in time. The first event occurs in all cretins and represents the prenatal action of thyroid hormone deficiency on brain development, transmitted vertically from mother to fetus, resulting in the neurological disorder of endemic cretinism. A consistent pattern and intensity of neurological, intellectual, and audiometric deficit is common to and equally present in all types of endemic cretin. The nature of these deficits points to an intrauterine insult to the developing fetal nervous system around the time of the midtrimester. The second event represents the postnatal action of thyroid hormone deficiency on somatic as well as brain development. Whereas previous workers had attributed the differences in the clinical presentation of endemic cretinism to the presence or absence of neurological features (i.e. prenatal hypothyroidism), the distinction between the types of endemic cretin can be related to the length and severity of postnatal thyroid hormone deficiency. Endemic cretins with predominant neurological features have had only transient hypothyroidism in the postnatal period, evidenced by their near normal thyroid function and by a lack of hypothyroid clinical features. By contrast, cretins with marked myxedematous features were characterized by permanent and severe postnatal thyroid hormone deficiency. These cretins, in addition to signs of neurological damage, were typically dwarfed, sexually immature, with marked clinical features of myxedema. This second event, influenced by the thyroid gland's morphologic response to its environment (goiter or thyroid atrophy), dictates the final clinical outcome. In conclusion, our hypothesis states that the clinical expression of endemic cretinism is determined by the sum of two pathophysiologic processes. The first process is fetal hypothyroidism which results in the neurological damage of the disorder and the second process is the duration and magnitude of postnatal hypothyroidism which dictates the final clinical appearance. PMID- 8499766 TI - Influence of frequency of previous pregnancies on the prevalence of thyroid nodules in women without clinical evidence of thyroid disease. AB - In a region with insufficient alimentary iodine supply (Kiel, Northern Germany) the prevalence of thyroid nodules was studied by means of ultrasonography in 212 healthy women (36-50 years old) in four groups of 53 women each with 0, 1, 2, and 3-5 previous pregnancies. Goiters were found in 28.3% (15 of 53) of the women without children and in 28.9% (46 of 159) of the women with children. There was no significant increase of goiter prevalence according to the number of pregnancies. We detected thyroid nodules in 21.2% (45 of 212). Only 9.4% (5 of 53) of the women without previous pregnancies had thyroid nodules, but 25.1% (40 of 159) of the women with pregnancies in the past had nodules, the difference being statistically significant (p < 0.05). We observed nodules in 11 of 53 women with 1 child (20.7%), in 11 of 53 women with 2 children (20.7%), and in 18 of 53 women with 3-5 previous pregnancies (33.9%). We propose that, in regions with borderline or insufficient alimentary iodine supply, accentuated iodine deficiency during pregnancies due to increase of iodine requirement is a probable cause for the higher prevalence of thyroid nodules in women with previous pregnancies. PMID- 8499767 TI - Neopterin, biochemistry and clinical use as a marker for cellular immune reactions. AB - Large amounts of neopterin are produced and released from human macrophages on stimulation with interferon-gamma. Neopterin is biologically stable, and it can be easily quantified in human body fluids. Neopterin measurements are useful to monitor allograft recipients to detect immunological complications. In autoimmune diseases, neopterin concentrations reflect the extent and activity of the disease. In infectious syndromes and in patients with cancer, neopterin concentrations provide prognostic information. In addition to providing clinically useful information, neopterin monitoring allows insight into the immunopathogenesis of a variety of diseases. PMID- 8499768 TI - Hereditary angioedema: uncomplicated maxillofacial surgery using short-term C1 inhibitor replacement therapy. AB - We report on the successful use of a pasteurized C1 inhibitor (C1-INH) concentrate during dental surgery of a patient affected by hereditary angioedema. The patient recovered fully without complications or side effects. Within 30 min, the first 1,000 U of C1-INH concentrate raised C1-INH concentration from 19 to 55% and function from 40 to 90% of the normal mean. When measured 4 h after the second injection, a further increase of the C1-INH concentration to 86% and a function of 106% relative to the normal mean was observed. Within 2 weeks C1-INH concentration returned to pretreatment level, while the function remained above this value. Serum liver enzyme values did not change and no anti-C1-INH alloantibodies were detected 10 months post-replacement therapy. We conclude that in patients affected by C1-INH deficiency, dental surgery and likely other traumatic procedures can be safely performed in conjunction with C1-INH replacement therapy even without preliminary treatment. PMID- 8499769 TI - Measurement and characterization of histamine and methylhistamine in human urine under histamine-rich and histamine-poor diets. AB - A radioimmunoassay for histamine was used to measure histamine and 1 methylhistamine (MH) in human urine samples. The detection limit of this assay was 2 ng/ml for histamine and 0.5 ng/ml for MH. Cation exchange high performance liquid chromatography (HPLC) on a Bio-Gel TSK SP-5 PW column with gradient elution was capable of separating histamine from its precursor L-histidine and its metabolites MH and 1-methylimidazole acetic acid (MIAA). The concentration of MH-immunoreactive materials in healthy volunteers with no dietary restrictions was 202 +/- 92 micrograms/24 h (mean +/- SD; n = 14). The excretion of MH-like material, expressed as micrograms of MH per 24 h, was not significantly different before or after the intake of histamine-rich food: 217 +/- 88 vs. 276 +/- 135 micrograms/24 h (n = 10). However, in urine samples collected in individual fractions, the levels of MH immunoreactivity were significantly increased after a histamine-rich meal in comparison to the corresponding fractions which were taken a day earlier at the same time intervals after a histamine-low diet (p < 0.03). HPLC characterization of MH immunoreactivity revealed the presence of histamine, MH and a compound with the same retention time as MIAA. The ratio of histamine, MH and MIAA in controls without dietary restrictions, as determined by HPLC analysis, was 50 +/- 6, 47 +/- 5 and 3 +/- 1%, respectively. After a histamine rich meal the ratio was 97 +/- 2% for histamine, 1% for MH and 2 +/- 1% for MIAA. PMID- 8499770 TI - Effects of interferon-alpha-2b on the clinical course, inflammatory skin infiltrates and peripheral blood lymphocytes in patients with severe atopic eczema. AB - Increased serum IgE and enhanced susceptibility to viral infections, decreased levels of interferons, lymphocytic skin infiltrates and IgE-bearing epidermal Langerhans cells are striking features in patients with atopic eczema (AE). Since the hyper-IgE syndrome is known to improve under alpha-interferon (alpha-IFN) therapy, we treated 7 patients with severe AE and high serum IgE exclusively with 3 x 10(6) units IFN alpha 2b thrice weekly for 3 months. Before treatment the skin infiltrates mainly consisted of CD3+/CD4+/TcR alpha/beta + lymphocytes, whereas the CD3+/CD8+ phenotype was limited to about 10% of cells. After 6 weeks of therapy, epidermal inflammation with CD4+ and CD8+ cells was reduced but dense infiltrates remained in papillary perivascular areas. Expression of TcR gamma/delta, HLA-DR and CD25 showed no significant changes. Initially high serum IgE and soluble CD23 as well as cell-bound IgE dropped under therapy, whereas a short-term elevation in serum IL-2 receptor was observed. On peripheral blood lymphocytes slightly reduced expression of HLA-DR, LFA-1, CD23 and ICAM-1 was seen after 100 days. LFA-3 expression became reduced in 4 patients, the CD4/CD8 ratio decreased in all cases. After an initial therapeutic response of all patients, significant longer-lasting improvement of the skin lesions could only be observed in 2 of 7 patients. The data of our long-term study suggest that systemic IFN alpha 2b treatment leads to a remarkable reduction in epidermal inflammation but does not significantly influence cutaneous cell subsets. Immunomodulatory effects became obvious by reduced peripheral cell subsets expressing TcR alpha/beta, MHC class II and adhesion molecules. PMID- 8499771 TI - CD23/Fc epsilon RII expression on phytohemagglutinin-A- or phorbol-12myristate 13acetate-Ca(2+)-activated human tonsil T cells. AB - The low-affinity Fc receptor for IgE, CD23/Fc epsilon RII, has been expressed in T cell lines and pathologic T cells, but its presence on normal human T cells is still debated. We studied the expression of CD23/Fc epsilon RII on purified T cells from normal peripheral blood mononuclear cells (PBMC) or tonsil T cells stimulated with 10 micrograms/ml phytohemagglutinin A (PHA) or phorbol 12myristate- 13acetate (PMA) Ca2+. Using two-dimensional flow cytometry, the tonsil T-cell-enriched population showed > 10% of CD23/Fc epsilon RII expression when coexpressed with the CD3 antigen. CD4+ T cells appear to be principally involved in the expression of CD23/Fc epsilon RII, although we were unable to detect a clear expression of CD23/Fc epsilon RII in PBMC that were activated with either PHA or PMA Ca2+. PHA stimulation resulted in the release of IgE binding factor (IgEBF). The induction of CD23/Fc epsilon RII expression in PHA- and PMA Ca(2+)-activated T cells was enhanced by IL-4, but not by IgE or IL-6. IL-4 also augmented the PHA- and PMA-Ca(2+)-induced release of IgEBF. The addition of supernatant from the Epstein-Barr virus (EBV)-infected cell line to PHA- or PMA Ca(2+)-stimulated tonsil T cells did not increase CD23/Fc epsilon RII expression. The expression of CD23/Fc epsilon RII mRNA was detected in RNA prepared from a tonsil T-cell-enriched population by Northern blot analysis. PMID- 8499772 TI - Steroid-induced depletion of mucosal mast cells and eosinophils in intestine of athymic nude rats. AB - In conventional rats, we have previously demonstrated that corticosteroid treatment caused macrophage engulfment and destruction of intestinal mucosal mast cells and eosinophils by 24 h without evidence of local tissue destruction, inflammation or secretion of rat mast cell protease II. As the growth and survival of these cells appear to be dependent on factors derived from T lymphocytes, we examined the response in congenitally athymic rnu/rnu rats and euthymic rnu/+ rats 35 days after parasitic infection. Rats were injected intraperitoneally with 1 mg dexamethasone and sections of jejunum were examined at 0, 7, 13 and 24 h. The numbers of mucosal mast cells significantly decreased in both groups and became less than 30% of the original values at 24 h. Tissue mast cell protease decreased similarly. However, protease in serum did not increase and there were no inflammatory changes at any time. The numbers of eosinophils also rapidly decreased and became less than 20% at 24 h in both rnu/rnu and rnu/+ rats. By electron microscopy, we saw granular changes (fusion) in mast cells and nuclear changes (apoptosis) in eosinophils by 7 h after corticosteroid in athymic rats. Macrophage engulfment of these cells was observed at 7 and 13 h. Our results suggest that inflammatory cell depletion by macrophages is not dependent on suppression of typical thymus-derived T lymphocytes, and may be due either to direct effects of steroids on the cells themselves, or indirectly upon cells other than T cells which normally supply maintenance and growth factors for them. PMID- 8499773 TI - The role of complement-derived chemotactic factors in lung injury induced by preformed immune complexes. AB - Our previous studies have suggested a role for complement fragments presumably activated by immune complexes in patients with hypersensitivity pneumonitis. The present study has shown that circulating complement depletion by cobra venom factor resulted in the reduction in severity of immune-complex-mediated pulmonary inflammation. The activity of chemotactic factors for neutrophils generated in bronchoalveolar lavage fluids in complement-depleted animals was significantly diminished to 61.2% compared to the undepleted animals. In addition, reduced activity of chemotactic factors resulted in a marked reduction of accumulation of neutrophils in bronchoalveolar lavage fluids indicating that chemotactic factors play an important role in the sequestration of neutrophils on the alveolar side of the lung. In conclusion, chemotactic factors in bronchoalveolar lavage fluids which preceded the accumulation of polymorphonuclear cells are partially derived from complement. PMID- 8499774 TI - Peptide-containing nerve fibers in human airways: distribution and coexistence pattern. AB - The occurrence, distribution and coexistence pattern of an array of neuropeptides and tyrosine hydroxylase in the human larynx, trachea, bronchi and lungs were studied by immunocytochemistry. A rich supply of nerve fibers containing vasoactive intestinal peptide (VIP) was seen close to blood vessels, glands and nonvascular smooth muscle. Pituitary adenylate cyclase-activating peptide (PACAP) containing fibers were numerous among bundles of smooth muscle. Moderate numbers of helospectin-containing nerve fibers were seen in the nonvascular smooth muscle. The majority of neuropeptide Y (NPY)-containing fibers were located in the nonvascular smooth muscle; some fibers also occurred around blood vessels and glands. Substance P (SP) and calcitonin gene-related peptide (CGRP)-containing fibers were generally few and distributed beneath the epithelium, among bundles of smooth muscle, around blood vessels and glands. A conspicuous finding was the lack of SP- and CGRP-containing fibers within the respiratory epithelium. Galanin containing nerve fibers were moderate in number among bundles of smooth muscle. Tyrosine hydroxylase-containing fibers were numerous around blood vessels and glands. The majority of the VIP-containing nerve fibers present in nonvascular smooth muscle also stored PACAP and helospectin. A subpopulation of VIP containing fibers in both vascular and nonvascular smooth muscle and around glands stored NPY. Additionally, galanin was found to occur in many VIP containing fibers located among bundles of smooth muscle. PMID- 8499775 TI - Gm allotypes as indicators of non-atopic and atopic bronchial asthma. AB - 69 Caucasian children, 34 with non-atopic and 35 with atopic bronchial asthma, demonstrated different, Gm-associated IgG antibody responsiveness. The non-atopic bronchial asthma group showed a preponderance of the Gm(a,'',g) haplotype, while the atopic study group showed a preponderance of the haplotype with the alternative allotypes on all IgG subclass loci, namely Gm(f,n,b). Patients with non-atopic bronchial asthma showed a significantly increased frequency of the phenotypes containing the Gm(a,'',g) haplotype, namely the Gm(a,'',g/a,'',g) and Gm(a,'',g/f,'',b), and an increased number of individuals were homozygous G2m('','') on the IgG2 locus. The 2 asthma groups showed different characteristic IgG subclass patterns, the non-atopic group with significantly decreased IgG2 and IgG3, especially those of the Gm(a,'',g/a,'',g) phenotype, and the atopic group with significantly increased IgG1 and IgG4, especially those of the Gm(f,n,b/f,n,b) phenotype. The characteristic IgG subclass patterns originate from the different Gm phenotypes found in the 2 groups. The results emphasize the presence of qualitatively and quantitatively different IgG molecules in non atopic and atopic bronchial asthma patients and show the interest in studying IgG genes and IgG molecules as markers of pathogenesis. G2m('','') homozygosity is a new important marker of non-atopic bronchial asthma. PMID- 8499776 TI - DNA typing with digoxigenin-11-dideoxyuridinetriphosphate-labelled oligonucleotide probes enables non-radioactive analysis using a dual detection system: application for screening HLA-DQA1 polymorphisms. AB - We describe a standardized, highly sensitive, nonradioactive detection procedure for HLA class-II typing of DQA1 alleles and suballeles which has important and cost-effective application in studying HLA disease associations. The procedure involves polymerase chain reaction-based target DNA sequence amplification and dot blotting followed by stringent hybridization with digoxigenin-11 dideoxyuridine triphosphate 3'-end-labelled allele-specific oligonucleotide probes. The dual detection system described here makes this procedure very versatile. PMID- 8499777 TI - Immediate and delayed (late-phase) dermal contact sensitivity reactions in guinea pigs. Passive transfer by IgG1 antibodies, initiation by mast cell degranulation, and suppression by soybean proteinase inhibitor. AB - Specific immediate and delayed (24-hour) local dermal reactivity to oxazolone and dinitrochlorobenzene (DNCB) was passively transferred to naive guinea pigs by the intradermal injection of immune guinea pig serum and its IgG1 fraction. In both actively sensitized and passively sensitized animals, neutrophils were the major cells present in the immediate reaction to the specific contactant. Basophils and mononuclear cells were the major cells present in the delayed reaction to the contactant. This late-phase reaction is, therefore, a cutaneous basophil hypersensitivity (CBH) response. The serum factor that passively transferred this CBH response was stable when heated at 56 degrees C for 1-4 h. Since transfer factor, cutaneous basophil hypersensitivity factor and guinea pig IgE are heat sensitive, these factors probably made little or no contribution to this response. Because proteinase inhibitors are known to inhibit mast-cell degranulation in vitro, we tested the effect of soybean proteinase inhibitor in vivo. This inhibitor suppressed both the immediate and the delayed skin reactivities mediated by intradermal contactant-specific IgG1. These studies support the following concept: IgG1 in guinea pigs (and IgE in human beings) sensitize mast cells to specific antigens. Such antigens degranulate mast cells, releasing histamine and other mediators for the immediate hypersensitivity reaction, and cause mast cells to produce cytokines that recruit basophils, eosinophils and mononuclear cells for the late-phase (CBH) reaction. PMID- 8499778 TI - Clonal analysis of human T-cell responses to fractionated house dust mite antigens (Dermatophagoides pteronyssinus). AB - In the present study, we investigated the cellular basis of house dust mite driven immune responsiveness in an atopic individual with perennial rhinitis. We established 40 human T-cell clones (CD3+, 4+, 8-) reactive to Dermatophagoides pteronyssinus (Dp) antigen under the restriction of HLA-DR. By using the crude Dp antigen and its 14 molecular weight (MW) fractions, we analyzed the distribution of T-cell-recognizing sites in the whole Dp extract. We tested T-cell-mediated immunity through two parameters; the identification of Dp fractions inducing T cell proliferation, and the ability of T-cell clones to secrete IL-2, IL-4, and IFN-gamma. According to a prominent peak among fraction-driven T-cell proliferation, we observed that T-cell clones that recognized 45,000- to 95,000 MW fractions were common, while clones reactive to 15,000- to 25,000-MW fractions were less frequent. Several clones were also reactive to antigens of Dermatophagoides farinae or other insects. Based on the responses of cloned T cells, we observed at least 9 distinct T epitopes in crude Dp antigen. These T cell clones had a heterogenous secretory pattern of cytokines. T-cell clones showed no association between their ability to produce regulatory cytokine and their recognition of particular Dp fractions. PMID- 8499779 TI - Fibrinogen: A new cardiovascular risk factor? PMID- 8499780 TI - Advising patients about fat intake. PMID- 8499781 TI - Health services. Our window to a tobacco-free world. PMID- 8499782 TI - Radiology rounds. Adrenal myelolipoma. PMID- 8499783 TI - New LCDC fax service. Putting current communicable disease information at your fingertips. PMID- 8499784 TI - Dermacase. Arthropod bites. PMID- 8499785 TI - Risks to hearing from a rock concert. AB - We measured noise exposure and temporary threshold shift (TTS) from a rock concert for 22 volunteers, using dosimetry, questionnaires, and audiometry. Most (81%) participants showed TTS of 10 dB or more 5 to 25 minutes after exposure; of these, 76% showed continued TTS at 40 to 60 minutes. Family physicians should counsel patients about the risks of recreational noise. PMID- 8499786 TI - Laboratory investigations in general practice. AB - Forty-eight family physicians completed a 10-item questionnaire about their use of laboratory investigations, and "ordered" tests for five clinical vignettes, estimating the cost of tests ordered. Physicians practising less than 10 years ordered more tests and overestimated the cost. Patients' expectations and risk of litigation affected test-ordering behaviour. Strategies to manage resources dedicated to laboratory investigations are explored. PMID- 8499787 TI - Effect of location on family medicine residents' training. AB - A survey of family medicine residents trained at community-based or hospital based centres suggested differences in experience and in career plans. Community based residents saw more patients in the same family, believed they knew the community better, made more housecalls, expected to use allied health professionals more frequently, and were more likely to choose a small community practice. PMID- 8499788 TI - Health promotion. Strategies for family physicians. AB - The current emphasis on health promotion raises questions among experienced health professionals. Many wonder whether such care differs from what we have always done and have doubts about cost effectiveness and government motives. This paper explores the latest meaning of the term health promotion, the evolution of strategies to promote health, and the implications of these strategies for practising family medicine. PMID- 8499789 TI - Advance directives in family practice. AB - Family physicians can play an important role in helping patients and their families to discuss life-sustaining treatments and to complete advance directives. This article reviews the legal status of, and empirical studies on, advance directives and addresses some important clinical questions about their use relevant to family practice. PMID- 8499790 TI - Critical appraisal of review articles. AB - Review articles are an important source of clinical information for family physicians. However, the volume of available reviews is vast and their scientific quality varies enormously. Family physicians must be able to identify trustworthy reviews quickly. This article outlines practical and flexible guidelines for critical appraisal and discusses the respective roles of review articles and original research reports in guiding clinical practice. PMID- 8499791 TI - Knee effusion after total knee replacement. AB - The various causes of effusions in artificial knees can be divided into four groups: implant related, technique related, interface problems, and infection. Diagnosis can be made from the patient's history and a clinical examination. Treatment is usually surgical revision. PMID- 8499792 TI - Asthma and anaphylactoid reactions to food additives. AB - Presumed allergic reactions to hidden food additives are both controversial and important. Clinical manifestations include asthma, urticaria, angioedema, and anaphylactic-anaphylactoid events. Most adverse reactions are caused by just a few additives, such as sulfites and monosodium glutamate. Diagnosis is suspected from the history and confirmed by specific challenge. The treatment is specific avoidance. PMID- 8499793 TI - Managing advanced multiple sclerosis. AB - Multiple sclerosis is one of the most common neurologic conditions in Canada. Many individuals with MS eventually develop the progressive form of the disease. The neurologic and psychosocial manifestations of the later stages of MS are numerous. Family physicians ought to have some understanding of patients with advanced MS and some knowledge of how to manage them. PMID- 8499794 TI - [The pneumococcal vaccine. Its efficacy in patients 55 and over]. AB - Three recent articles are examined in which research using the double-blind randomised clinical trial, the case control study, and the quasi-cohort study is described. Understanding the advantages and disadvantages of these methods makes it easier to grasp the pneumococcal vaccine controversy and make an informed choice. PMID- 8499795 TI - Seizure prophylaxis for brain tumour patients. Brief review and guide for family physicians. AB - Brain tumours are relatively uncommon, but family physicians are sometimes confronted with the somewhat unnerving task of carrying on the day-to-day management of these patients. The authors examine some of the problems encountered in preventing seizures among brain tumour patients. Using illustrative clinical cases and a review of the relevant literature, guidelines are provided for the institution, maintenance, and in some cases discontinuation of seizure prophylaxis for this group of patients. PMID- 8499796 TI - Mutagens and carcinogens in foods. Epidemiologic review. AB - Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID- 8499797 TI - Achalasia in pregnancy. A case of a rare coexistence. PMID- 8499798 TI - Change and challenge: Part 1. PMID- 8499799 TI - Interview with Kawohionapuaikai'ulani (the most beautiful flower in heaven). Interview by Ina May Gaskin. PMID- 8499800 TI - Direct entry midwifery education: caught in the middle of the maternity care crisis and a political-educational debate. PMID- 8499801 TI - There is something drastically wrong with the way we organize health care in the United States. PMID- 8499802 TI - Japan: pill vetoed for fear of AIDS. PMID- 8499803 TI - On midwifery exams. PMID- 8499804 TI - "My version". PMID- 8499805 TI - I'm six and a half months pregnant and have been predominantly a vegetarian for eight years. PMID- 8499806 TI - The cutting edge. 104 hospitals with the highest cesarean section rates (37% and over). PMID- 8499807 TI - Children at birth. PMID- 8499808 TI - Midwifery is not the practice of medicine. PMID- 8499809 TI - Interview with Sue Cookson. Interview by Ina May Gaskin. PMID- 8499811 TI - WHO at the crossroads. PMID- 8499810 TI - The selected list. PMID- 8499812 TI - Universal named testing of pregnant women for HIV. PMID- 8499813 TI - Where are the women in studies of coronary heart disease? PMID- 8499814 TI - Paternal preconceptional radiation exposure in the nuclear industry and leukaemia and non-Hodgkin's lymphoma in young people in Scotland. AB - OBJECTIVE: To determine if a relation exists between paternal exposure to relatively high levels of radiation in the Scottish nuclear industry and the risk of leukaemia and non-Hodgkin's lymphoma is subsequently conceived children. DESIGN: Matched case-control study with three controls for each case. SETTING: The whole of Scotland. SUBJECTS: The fathers of 1024 children with leukaemia and 237 children with non-Hodgkin's lymphoma diagnosed in Scotland below the age of 25 among those born in Scotland since nuclear operations began (in 1958) and the fathers of 3783 randomly chosen controls. The fathers of 80 children with leukaemia and 16 with non-Hodgkin's lymphoma in north Cumbria were also covered since some workers at one Scottish nuclear site live over the border in that area. Details of all fathers were then matched against records of the nuclear industry. MAIN OUTCOME MEASURES: Paternal preconceptional radiation exposures, particularly relatively high levels, both lifetime and in the six and three months before conception. RESULTS: No significant excess was observed in any subgroup and there was no significant trend: fathers of three controls but no cases were exposed to lifetime preconceptional levels of 100 mSv or greater (Fisher's exact p value 0.84). In the six months before conception, fathers of two cases and three controls received 10 mSv or more, odds ratio 2.3 (95% confidence interval 0.31 to 17.24). In the three months before conception the fathers of one case and two controls received 5 mSv or more, odds ratio 1.7 (0.10 to 30.76). The results for leukaemia and non-Hodgkin's lymphoma combined were similar. CONCLUSIONS: No significant excess of leukaemia or of leukaemia and non Hodgkin's lymphoma was found at any radiation level in any preconceptional period. PMID- 8499815 TI - Effects of computer generated reminder charts on patients' compliance with drug regimens. AB - OBJECTIVE: To investigate whether a reminder chart improved patients' compliance with their drug regimen after discharge from hospital. DESIGN: Patients were randomly allocated to one of four groups. Two groups received the reminder chart: one also received routine counselling from a nurse and the other received structured counselling from a pharmacist, which included an explanation of the reminder chart. The other two groups received only counseling, either from a nurse or from a pharmacist. Patients were visited about 10 days later: they were questioned about their drug regimen, and their compliance was measured by tablet counting. SETTING: The pharmacy in a district general hospital and patients' homes. PATIENTS: 197 patients being discharged from hospital who were regularly taking two or more drugs. INTERVENTION: An individualised reminder chart, which listed each person's medicines and when they were to be taken and was automatically generated by a medicine labelling computer. MAIN OUTCOME MEASURES: Patient's compliance with and knowledge of their drug regimen. MAIN RESULTS: Of the patients who received the reminder chart, 83% (95% confidence interval 74% to 90%) correctly described their dose regimen compared with 47% (37% to 58%) of those without the chart (p < 0.001). The mean compliance score was 86% (81% to 91%) in both groups not given the reminder chart; 91% (87% to 94%) in the group given the chart without an explanation; and 95% (93% to 98%) in the group given the chart and an explanation. A mean compliance score of > 85% was achieved by 63% (53% to 73%) of patients without a reminder chart and by 86% (78% to 93%) of those receiving the chart (p < 0.001). CONCLUSIONS: An automatically generated reminder chart is a practical and cost effective aid to compliance. PMID- 8499816 TI - Abnormalities of sleep in patients with the chronic fatigue syndrome. AB - OBJECTIVE: To determine whether patients with the chronic fatigue syndrome have abnormalities of sleep which may contribute to daytime fatigue. DESIGN: A case control study of the sleep of patients with the chronic fatigue syndrome and that of healthy volunteers. SETTING: An infectious disease outpatient clinic and subjects' homes. SUBJECTS: 12 patients who met research criteria for the chronic fatigue syndrome but not for major depressive disorder and 12 healthy controls matched for age, sex, and weight. MAIN OUTCOME MEASURES: Subjective reports of sleep from patients' diaries and measurement of sleep patterns by polysomnography. Subjects' anxiety, depression, and functional impairment were assessed by interview. RESULTS: Patients with the chronic fatigue syndrome spent more time in bed than controls (544 min v 465 min, p < 0.001) but slept less efficiently (90% v 96%, p < 0.05) and spent more time awake after initially going to sleep (31.9 min v 16.6 min, p < 0.05). Seven patients with the chronic fatigue syndrome had a sleep disorder (four had difficulty maintaining sleep, one had difficulty getting to sleep, one had difficulty in both initiating and maintaining sleep, and one had hypersomnia) compared with none of the controls (p = 0.003). Those with sleep disorders showed greater functional impairment than the remaining five patients (score on general health survey 50.4% v 70.4%, p < 0.05), but their psychiatric scores were not significantly different. CONCLUSIONS: Most patients with the chronic fatigue syndrome had sleep disorders, which are likely to contribute to daytime fatigue. Sleep disorders may be important in the aetiology of the syndrome. PMID- 8499818 TI - Inaccuracy of FHSA registers: help from electoral registers. PMID- 8499817 TI - Coronary artery surgery: are women discriminated against? AB - OBJECTIVE: To determine whether the sex differences in access to cardiac surgery observed in the United States exist in the United Kingdom. DESIGN: Retrospective analysis of routinely collected data. SETTING: South West Thames and North West Thames regional health authorities. SUBJECTS: 8564 patients discharged from hospital with a principal diagnosis of coronary heart disease in 1987-8 in South West Thames region and 15243 discharges in North West Thames region in 1990-1. MAIN OUTCOME MEASURES: Performance of angiography or coronary artery bypass surgery. RESULTS: In all age groups and among patients with a principal diagnosis of either angina or chronic ischaemia men were significantly more likely than women to undergo revascularisation in both regions. Using multiple logistic regression to control for potential clinical and demographic confounders, the male to female odds ratio for revascularisation among all cases was 1.59 (95% confidence interval 1.25 to 2.03) in South West Thames region and 1.47 (1.32 to 1.63) in North West Thames region. CONCLUSION: There appears to be a systematic difference in the treatment received by men and women in the United Kingdom. The reasons for this are uncertain. PMID- 8499819 TI - Hemiplegia after measles, mumps, and rubella vaccination. PMID- 8499820 TI - Hyponatraemic convulsion associated with desmopressin and imipramine treatment. PMID- 8499821 TI - Muscle cramps related to corticosteroids. PMID- 8499822 TI - Psychomotor retardation and semistuporous state with paroxetine. PMID- 8499823 TI - Treatment of streptococcal pharyngitis with amoxycillin once a day. AB - OBJECTIVE: To evaluate treatment of group A beta haemolytic streptococcal pharyngitis with amoxycillin once daily compared with phenoxymethylpenicillin three or four times a day. DESIGN: Randomised controlled study of consecutive patients presenting with symptoms suggestive of group A beta haemolytic streptococcal pharyngitis in whom culture of a throat swab yielded positive results. SETTING: Five family medicine practices. SUBJECTS: 157 patients aged over 3 years who required treatment with antibiotics. MAIN OUTCOME MEASURES: Clinical response, bacteriological response, days at work and school lost, and compliance. RESULTS: During the period of the study 393 patients presented with symptoms suggesting streptococcal pharyngitis; 157 of them had throat swabs that yielded positive results on culture. Eighty two were treated with phenoxymethylpenicillin and 75 with amoxycillin. No difference was observed in the clinical response, days at work and school lost (139 days for 64 patients taking phenoxymethylpenicillin v 100 days for 57 patients taking amoxycillin; p > 0.2), or residual positive cultures after two days (6 (7.3%) v 3 (4%); p > 0.5). A significant difference in the bacteriological response was found after 14 days (5 (6.1%) v 0; p < 0.04) with no positive cultures observed in the amoxycillin group. CONCLUSIONS: These findings support the hypothesis that amoxycillin once daily is as effective as phenoxymethylpenicillin in the treatment of group A beta haemolytic streptococcal pharyngitis. PMID- 8499824 TI - Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing. AB - OBJECTIVE: To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens. DESIGN: Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae. SETTING: Family practice teaching clinic in a university hospital. PATIENTS: 411 women presenting for a smear test. MAIN OUTCOME MEASURES: Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear. RESULTS: Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups. CONCLUSION: Reports of inflammatory changes on cervical smear testing are a poor indicator of infection. PMID- 8499825 TI - Diagnosis and treatment of malaria in Britain. PMID- 8499826 TI - Sample size for beginners. AB - The common failure to include an estimation of sample size in grant proposals imposes a major handicap on applicants, particularly for those proposing work in any aspect of research in the health services. Members of research committees need evidence that a study is of adequate size for there to be a reasonable chance of a clear answer at the end. A simple illustrated explanation of the concepts in determining sample size should encourage the faint hearted to pay more attention to this increasingly important aspect of grantsmanship. PMID- 8499827 TI - The new NHS: the second year. Budget holding: here to stay? PMID- 8499828 TI - ABC of sleep disorders. Nocturnal asthma. PMID- 8499829 TI - Thyroid eye disease. Disfiguring and capricious condition. PMID- 8499830 TI - Thyroid eye disease. More treatment options. PMID- 8499831 TI - Thyroid eye disease. Patients need joint care. PMID- 8499832 TI - Bad teeth and myocardial infarction. Smokers neglect their teeth. PMID- 8499833 TI - Bad teeth and myocardial infarction. Roles for white cells and fibrinogen. PMID- 8499834 TI - Transgenic pigs under stress. PMID- 8499835 TI - New clinics for HIV testing. Improve public access. PMID- 8499836 TI - New clinics for HIV testing. New clinics offer choice. PMID- 8499837 TI - New clinics for HIV testing. Upgrade existing services. PMID- 8499838 TI - Antenatal screening for Down's syndrome. PMID- 8499839 TI - Effect of tamoxifen on bone. PMID- 8499840 TI - Racial discrimination. Prejudice exaggerated. PMID- 8499841 TI - Racial discrimination. Secrecy not the answer. PMID- 8499842 TI - Guidelines for HIV. Health workers have rights too. PMID- 8499843 TI - Guidelines for HIV. Health workers need protection. PMID- 8499844 TI - Guidelines for HIV. Sensible approach restores confidence. PMID- 8499845 TI - HIV Guidelines for HIV. Cost of compulsory HIV testing. PMID- 8499846 TI - Chlamydial respiratory infections. PMID- 8499847 TI - Patients with brain injuries. PMID- 8499848 TI - Treating hyperhidrosis. PMID- 8499849 TI - Screening: reasons to be cautious. PMID- 8499850 TI - Health care reform. PMID- 8499851 TI - Open access upper gastrointestinal endoscopy. PMID- 8499852 TI - Influence of socioeconomic factors on attaining targets for reducing teenage pregnancies. AB - OBJECTIVE: To determine the rate of pregnancy and outcome in teenagers in areas of different socioeconomic conditions, and to assess the implication for achievement of government and local targets in reducing unwanted pregnancies in teenagers. DESIGN: Records of pregnancies were obtained from hospital discharge files and rates of live and still births and abortions calculated for each postcode sector. Postcodes were grouped by categories of deprivation and by local government district. SETTING: Tayside, Scotland. SUBJECTS: Teenage girls admitted to National Health Service hospitals for delivery or abortion in 1980-90. MAIN OUTCOME MEASURES: Conception in girls aged under 16 by area of residence and relative proportion leading to live births or terminations. Rate of different outcomes in girls under the age of 20 by area of residence. RESULTS: The pregnancy rate in girls aged under 16 was three times as high, and in all girls under 20 six times as high in the most deprived areas as in the most affluent areas. The proportion of teenage pregnancies ending in abortions was higher in the affluent areas, where two out of three ended in abortion compared with one out of four in the deprived areas. CONCLUSIONS: Although there was a higher pregnancy rate in teenagers in more deprived areas, the proportion ending in abortion was greater in more affluent areas, possibly due to social and parental pressure. The wide geographical variation in patterns of teenage pregnancy indicates the need for a small area rather than a regional approach to setting targets and devising measures of achieving them. PMID- 8499853 TI - Risk factors for development of microalbuminuria in insulin dependent diabetic patients: a cohort study. Microalbuminuria Collaborative Study Group, United Kingdom. AB - OBJECTIVE: To investigate the risk factors for the development of persistent microalbuminuria in insulin dependent diabetic patients. DESIGN: Four year follow up of a cohort of diabetic patients. SETTING: Outpatient departments of teaching and district general hospitals in England. SUBJECTS: 148 non-microalbuminuric, non-hypertensive insulin dependent diabetic patients. MAIN OUTCOME MEASURES: Urinary albumin excretion rate and arterial blood pressure. RESULTS: 137 patients completed four year follow up, of whom 11 developed persistent microalbumin-uria (albumin excretion rate > or = 30 micrograms/min on at least two consecutive occasions), giving a cumulative frequency of 8%. 103 remained normoalbuminuric and 23 exhibited intermittent microalbuminuria. At baseline the persistent microalbuminuric group had had significantly raised blood pressure (mean 137.9 (SD 14.9)/82.3 (7.6) v 123.5 (13.2)/72.8 (9.1) mm Hg), glycated haemoglobin concentration 10.4% (2.0%) v 8-9% (2.0%), and albumin excretion rate (median (interquartile range) 17.5 (13.0-22.3) v 4.8 (3.7-6.7) micrograms/min) (p < 0.05 for all) compared with the normo-albuminuric group. Blood pressure and glycated haemoglobin remained significantly higher in the persistent microalbuminuric group throughout the study (p < 0.05). Multiple regression analysis showed initial albumin excretion rate, blood pressure, and smoking to be significant determinants of persistent microalbuminuria (p < 0.02). CONCLUSION: In insulin dependent diabetic patients with poor glucose control, which may initially increase albumin excretion rate, an early rise of arterial pressure and smoking are implicated in the development of persistent microalbuminuria. PMID- 8499854 TI - Variable mercaptopurine metabolism in children with leukaemia: a problem of non compliance? PMID- 8499855 TI - Prescribing costs in dispensing practices. AB - OBJECTIVE: To examine differences in prescribing between dispensing and non dispensing practices. SETTING: The 108 practices covered by Lincolnshire Family Health Services Authority. DESIGN: Analysis of prescribing data for 1990-1 from PD2 reports from the Prescription Pricing Authority in relation to data on practice characteristics obtained from Lincolnshire Family Health Services Authority; and aggregated level 3 prescribing and cost information (PACT data) for 10 selected drugs from the Prescription Pricing Authority to examine amounts prescribed. MAIN OUTCOME MEASURES: Prescribing cost per patient, items per patient, and cost per item in dispensing and non-dispensing practices. RESULTS: Dispensing practices had higher prescribing costs per patient than non-dispensing practices. This difference held for non-dispensing patients within dispensing practices. Structural features failed to explain the differences in prescribing cost, except for the higher numbers of elderly patients in dispensing practices (which explained 13% of the difference) and the number of partners (5%). The main determinant of the difference was the lower use of generic drugs in dispensing practices (84%). Dispensing patients were prescribed lower quantities of drugs on average for each item. CONCLUSIONS: Dispensing practices could reduce their prescribing expenditure to that of non-dispensing practices by increasing their prescribing of generic drugs. The shorter prescribing intervals for dispensing patients may be due to dispensing fees being related to the number of prescribed items. PMID- 8499856 TI - Prophylaxis against malaria for travellers from the United Kingdom. Malaria Reference Laboratory and the Ross Institute. AB - To provide revised guidance on malaria prevention for the medical advisers of travellers from the United Kingdom going overseas to malarious areas, a committee of those most involved in giving advice and with specialist expertise in the United Kingdom agreed a policy document. There is a need for all travellers to be aware of the risk of malaria and to take measures to avoid being bitten by anopheline mosquitos, especially at night. Chemoprophylaxis is recommended also for most malarious areas. In view of the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and proguanil, mefloquine is added to the list of recommended drugs for more areas than in the past, and is the preferred chemoprophylactic for east and central Africa. Chloroquine with proguanil continues to be widely appropriate. Detailed recommendations are given for each country. Travellers out of reach of prompt medical assistance are advised to carry treatment doses of a standby drug: halofantrine, Fansidar, or quinine. The need for full compliance with any regimen is emphasised. No prophylaxis is totally effective. Malaria must be considered in the differential diagnosis of any fever in someone who has visited an endemic area within the past year. PMID- 8499857 TI - Thomas McKeown and Archibald Cochrane: a journey through the diffusion of their ideas. AB - In the 1970s Thomas McKeown and Archibald L Cochrane were two of the most influential voices in criticizing the dominance of medical thinking. A bibliometric study of the citations to McKeown's The Role of Medicine: Dream, Mirage or Nemesis and Cochrane's Effectiveness and Efficiency: Random Reflections on Health Services was performed from the publication of each book until 1988 to study how their ideas have been disseminated. During the study period 430 papers in the Science Citation Index or the Social Sciences Citation Index cited Cochrane's book, 133 cited McKeown's, and 166 cited both. The citations came mainly from original papers published in journals of internal medicine or public health and epidemiology (35%) and written by authors from the United States or the United Kingdom. Cochrane's book was cited most frequently in medical journals, suggesting a higher degree of penetration of his ideas among medical scientists. Although the dominance of original papers among the citations suggests that these books have been important in stimulating new knowledge, the main problems that McKeown and Cochrane identified--namely, the relatively small impact of clinical medicine on health outcomes and the poor use of scientific methods in clinical practice--are still with us. PMID- 8499858 TI - The new NHS: the second year. East Birmingham: all change. PMID- 8499859 TI - Tuberous sclerosis and polycystic kidney disease. PMID- 8499860 TI - ABC of sleep disorders. Unexpected presentations of sleep apnoea: use of CPAP in treatment. PMID- 8499861 TI - Letter from Peru. A country torn apart by violence. PMID- 8499862 TI - Low back pain. Abnormalities rare on x ray examination. PMID- 8499863 TI - Low back pain. Consider compromised blood supply. PMID- 8499864 TI - Low back pain. Related to emotional disorder. PMID- 8499865 TI - Low back pain. Serial epidural injections effective. PMID- 8499866 TI - Mycobacteria and sarcoidosis. Clinical studies support link. PMID- 8499867 TI - Mycobacteria and sarcoidosis. BCG ineffective against sarcoidosis. PMID- 8499868 TI - Gangliosides in neurological diseases. PMID- 8499869 TI - Urinary albumin excretion. Timed urine collections advisable. PMID- 8499870 TI - Urinary albumin excretion. Intermittent excreters warrant investigation. PMID- 8499871 TI - Oral versus intramuscular vitamin K in newborn infants. PMID- 8499872 TI - Informed consent. PMID- 8499873 TI - SHO training. Consultants need time to teach. PMID- 8499874 TI - SHO training. Assessment initiative in accident and emergency. PMID- 8499875 TI - SHO training. Medical unit struggles with proposals. PMID- 8499876 TI - SHO training. Partial shifts difficult in medicine. PMID- 8499877 TI - [Values of the flow-volume curve in healthy children from Cracow]. AB - Basing on results of spirometric tests performed in 180 healthy children from Cracow (age range 8-16 years) the following parameters of the flow-volume curve were calculated: FVC, FEV1, FEV1/FVC, PEF, FEF25-75%, FEF50%, FEF75%. Due to statistically significant differences in the above mentioned indices related to sx, normograms were calculated for boys and girls. It was found that the exponential function characterises the best relation between volume and height, and the multinomial function flow values and height. PMID- 8499878 TI - [Effect of treatment at a health resort in a plains climate on peak expiratory flow values in preschool children with respiratory disorders]. AB - PEF is the most widely used parameter to assess airflow limitations of the airways. The aim of the study was to assess the value of climatic treatment in the sub-mountainous region on PEF values in pre school age children with various respiratory diseases, inhabitants of the upper silesian industrial region. In 113 children (age 4-6) PEF values were recorded at the beginning and end of the 21 day stay at the sanatorium. PEF was recorded using the Vitalo-graph meter. The results of the study revealed an increase of PEF values was statistically significant. PMID- 8499879 TI - [Aspirin-sensitive urticaria; a clinical study]. AB - In the paper clinical characteristics of patients with aspirin-induced urticaria were performed. The group of 71 patients, 49 women (69%) and 22 men (31%), mean age of sensitivity symptoms demonstration--32.5 years, underwent allergological, laryngological and histamine dihydrochloride inhalatory tests. Nasal polyps were found in 2 persons (2.8%), atopic diseases in 23 persons (32.3%) and at least one feature of atopy in 37 persons (51.9%). 49 subjects (69%) suffered from urticaria which was not associated with ingestion of aspirin. In 22 patients urticaria developed solely due to aspirin. Urticaria not associated with aspirin had been presents for 2 weeks to 30 years before the onset of sensitivity to aspirin. The authors conclude that aspirin-sensitive urticaria results from concomitance of two different phenomena in one person, i.e. sensitivity to aspirin and urticaria not associated with ingestion of the drug. PMID- 8499880 TI - [Urticaria-angioedema type of sensitivity to aspirin and other nonsteroidal anti inflammatory drugs; diagnostic value of anamnesis and challenge tests with acetylsalicylic acid in detecting this sensitivity]. AB - The aim of the paper was to estimate the value of challenge tests with acetylsalicylic acid in diagnosis of ASA-induced urticaria. The study was performed in 71 persons with suspected urticaria/angioedema type of sensitivity to ASA. The anamnesis confirmed sensitivity in 67 examined patients (94.4%) and showed that the sensitive patients usually suffered from extensive urticaria (37 persons, i.e. 55.5%) after ingestion of ASA. Eight persons (12%) reacted with loss of consciousness and 4 (6.0%) with oedema of the larynx. Oral challenge test with acetylsalicylic acid was performed in 53 examined persons, in 49 (92.4%) of which it was positive. Threshold doses of acetylsalicylic acid ranged from 40 to 300 mg. In 11 persons the test was repeated and in 8 performed three times. It was observed that both the threshold acetylsalicylic acid doses and the time of appearance of the sensitivity symptoms were changeable. All ASA-sensitive reacted to indomethacin in the similar way as to ASA. Paracetamol, on the other hand, was well tolerated by all 25 tested patients with urticaria/angioedema type of sensitivity to ASA. PMID- 8499881 TI - [Effect of correcting funnel chest on respiratory function]. AB - The authors discuss the results of pulmonary function tests performed at rest in 25 patients treated for pectus excavatum. Surgical correction of the lesion was performed by resection of the deformed costal cartilages, longitudinal and transversal sternotomy, stabilization of the anterior chest wall with Kirschner wires. Control tests carried out 6 months following the surgical correction. In cases of severe deformation of the chest wall a decrease of pulmonary function indices was evident. Following the surgical correction all spirometric indices increased. PMID- 8499882 TI - [Usefulness of microscopic examination of bronchial cellular material for lung cancer diagnosis and determination of cell type]. AB - Results of microscopical examination of airway material (sputum, bronchoscopy) were analysed in 563 patients with lung cancer. Bronchoscopic material was examined from all patients, while sputum only from 352. Sputum was always analysed prior examination of bronchoscopic material cancer cells were found in material from lower airways in 366 patients (65%), correct cell typing was achieved in 286 (78.1%). Cancer cells were present in the sputum in 28.1% of the analysed patients and in 60% of the material obtained during bronchoscopy. In 178 patients with squamous cell lung cancer, cancer cells were found in 64.9% while correct cell typing was found in 83.4%. In 183 patients with small cell lung cancer, neoplastic cells were found in 72.6% of the cases while correct cell typing was achieved in 88.7%. In 144 patients with adenocarcinoma cancer cells were found in 53.4% while correct typing was present in 64.9%. In 18 cases of large cell lung cancer, cancer cells were present in 50%, and correct cell typing was achieved in 22.2%. Differences were statistically significant between small cell lung cancer and adenocarcinoma. Correct cell typing was statistically more often significant in patients with squamous cell lung cancer or SCLC in comparison with the other types. Significant results of positive cytology was found when analysing localisation of the tumor. In cases of central tumor cytology was positive in 60% of the cases, while in peripheral tumors it was positive only in 43.9% of the cases. The size of the tumor did not affect the sensitivity of the cytological examination. PMID- 8499883 TI - [The problem of allergic pulmonary aspergillosis in children in light of personal observations]. AB - 67 children (age range 4-17 years) with severe asthma were examined for the presence of allergic pulmonary aspergillosis 28 of these underwent long term steroid therapy. The following parameters were analysed: medical history, clinical state, chest radiograms, microbiological examination of the sputum, precipitating IgG antibodies, skin prick tests with aspergillus, level of specific IgE antibodies. The authors did not find any single child that met the diagnostical criteria of allergic pulmonary aspergillosis. Only in 4 serum specific IgE antibodies were found but the precipitin and skin prick tests were negative. The children did not present typical clinical symptoms of pulmonary allergic aspergillosis. It seems worthwhile to re-examine these children in a few years. PMID- 8499884 TI - [Plasma cell granuloma of the lung]. PMID- 8499885 TI - [Non-malignant esophago-bronchial fistulas]. AB - Pathogenesis, diagnosis and treatment of non-malignant esophago-bronchial fistulas is discussed. A case report of a 60 year old woman with such a disorder is presented. Surgical treatment completely cured this patient. PMID- 8499886 TI - [Thymoma as a rare case of mediastinal tumor]. PMID- 8499887 TI - [Peribronchial granulomatosis imitating the neoplastic process]. PMID- 8499888 TI - [Diagnostic difficulties with pleural mesothelioma]. AB - An increase in the incidence of mesothelioma is presently seen. The current views on pathogenesis and diagnosis of this malignancy are presented. Early and final diagnosis are hampered by heterogenecity of clinical, macroscopic and microscopic features of this tumor. PMID- 8499889 TI - [Bronchial carcinoids]. PMID- 8499890 TI - [Bronchiolitis in infancy as a cause of wheezing]. PMID- 8499891 TI - Probiotic use of lactobacilli in the human female urogenital tract. PMID- 8499892 TI - Characterization of the serum requirement for macrophage-mediated killing of Treponema pallidum ssp. pallidum: relationship to the development of opsonizing antibodies. AB - Serum pools were collected from rabbits bled at various times after intra testicular infection with Treponema pallidum ssp. pallidum. These were tested for their ability to opsonize T. pallidum and promote killing of the organisms by macrophages. Compared to normal sera, significant opsonization was first seen on day 10 of infection as measured by both ingestion (P < 0.001) and macrophage mediated killing (P = 0.006); significant levels of functional antibodies persisted through 300 days of infection. Although opsonic activity peaked early in infection, antibodies that promoted optimal macrophage-mediated killing developed much later, suggesting that these two functions may represent activities of antibodies with differing specificities or affinities. The initial development of antibodies that augment both phagocytosis and killing corresponds with the in vivo clearance of treponemes from the primary site of infection. These observations support the hypothesis that macrophages are the major effector mechanism for elimination of T. pallidum during early syphilis infection. PMID- 8499893 TI - Simplified method for the interpretation of immunoblots for Lyme borreliosis. AB - Interpretation of immunoblot results for Lyme borreliosis remains an area of controversy. This study was undertaken to devise a simple method which incorporated distinctions between specific and non-specific bands. A numerical value was assigned to bands reflecting their relative importance. This scheme was evaluated with sera from 61 forestry workers, which were previously tested by immunoblotting and interpreted subjectively. These results were reported as five separate categories representing levels of reactivity. A total of 72% (44) of sera fell into the same categories as they were originally reported. The method was also assessed with 40 sera routinely submitted for Lyme borreliosis serology. These were interpreted by two members of staff without previous experience of immunoblotting. Their results gave 80% and 72.5% agreement with those of an experienced person used to reading immunoblots for Lyme borreliosis. PMID- 8499894 TI - The effect of Mycoplasma arthritidis infection on the kinetics of colloidal carbon clearance in mice. AB - The activity of phagocytes from A/J mice was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. Phagocytic activity was significantly depressed 12 h post-infection (P = 0.001) and returned to normal values at 24 h. For animals examined 2 and 7 days post-infection, the overall phagocytic activity increased significantly (P < 10(-4). Phagocytic activity gradually decreased and returned to that of the control group by the end of the fourth week. The relative weights of liver and spleen were significantly increased from the 2nd day post infection (P = 0.0028 and P = 0.0014 respectively) and remained increased until the end of the experiment. The early depressive effect on phagocytic activity may be related to superantigen activity with the production of mediators such as macrophage deactivating factor. The later expansion of the macrophage population might bring about the stimulation of autoreactive clones of T and B cells and be responsible for the chronic arthritis that developed in the mycoplasma treated mice. PMID- 8499895 TI - Immunological activity of lipopolysaccharide of Helicobacter pylori on human peripheral mononuclear blood cells in comparison to lipopolysaccharides of other intestinal bacteria. AB - Lipopolysaccharide of Helicobacter pylori was tested for its mitogenicity and for its ability to stimulate cytokine release in human peripheral blood mononuclear cells (PBMC) of healthy and H. pylori-infected blood donors. Mitogenicity in PBMC induced by H. pylori LPS was similar to that induced by Campylobacter jejuni lipopolysaccharide, but lower than that induced by Escherichia coli lipopolysaccharide in the H. pylori negative blood donor group. Furthermore, H. pylori LPS was able to induce tumour necrosis factor (TNF) interleukin 1 (IL-1) and interleukin 6 (IL-6) secretion of PBMC. Compared with the ability of C. jejuni and E. coli lipopolysaccharides to stimulate cytokine release, H. pylori lipopolysaccharide induced a significantly lower TNF and IL-1 secretion of PBMC than the other tested bacterial lipopolysaccharides. Similar amounts of IL-6 release were obtained by stimulation of PBMC with H. pylori and C. jejuni lipopolysaccharides, whereas a higher IL-6 release was measured by stimulation with E. coli lipopolysaccharide. The results of this study suggest that H. pylori lipopolysaccharide has a lower immunological activity than lipopolysaccharides of other intestinal bacteria. This is probably due to its unusual acylation and phosphorylation pattern of lipid A. PMID- 8499896 TI - Antibodies to Bordetella pertussis adenylate cyclase toxin in neonatal and maternal sera. AB - To investigate the high prevalence among infants of antibodies to Bordetella pertussis adenylate cyclase toxin (ACT), cord-blood sera were examined for antibodies to ACT, filamentous hemagglutinin (FHA) and pertussis toxin (PT) using immunoblot analysis. Antibodies reactive with ACT were the most prevalent in neonatal sera. Similar reactivity of IgG with ACT was found in each sample of a given neonatal-maternal pair, yet IgM reactive with ACT was virtually absent in neonatal sera, suggesting that antibodies to ACT are maternally derived. Antibodies to ACT might come from infection or childhood vaccination of the mothers since pertussis vaccines from all US manufacturers elicited antibodies to ACT in mice. Alternatively, these antibodies may have been elicited by a cross reactive antigen such as Escherichia coli alpha-hemolysin, since all of the neonatal and maternal sera contained antibodies reactive with alpha-hemolysin. PMID- 8499897 TI - Heat-labile and heat-stable haemolysins of Campylobacter jejuni. AB - During studies on the virulence mechanisms of Campylobacter jejuni clinical isolates it became apparent that some strains produced one or more haemolysins and some did not. There was no great difference between Group C (cholera-like) strains and Group D (dysentery-like) strains. The protein haemolysin(s) showed a spectrum of activity against erythrocytes from different animals; with maximum activity against rabbit and minimal activity against chicken erythrocytes. The results suggested a two-stage activation mechanism for haemolysis which involved a multi-hit lytic activity. It was concluded that the C. jejuni haemolysins were not identical to those described in other organisms and they may be involved in iron acquisition in vivo. PMID- 8499898 TI - Isolation of the human Xp21 glycerol kinase gene by positional cloning. AB - The gene for human glycerol kinase deficiency (GK) maps in Xp21.3 in a critical region of about 50-250 kb located distal to the Duchenne muscular dystrophy gene (DMD) by analysis of patient deletions and YAC contigs. We have used a genomic exon amplification strategy to isolate potential exons from two cosmids which mapped to this interval. The genomic exons were used to isolate six overlapping cDNA clones from human fetal liver which encode the X-linked glycerol kinase gene. The cDNA clones map to cosmids, YAC clones and deletions in patients which define the GK critical region and also hybridize to several autosomal fragments and one Xq fragment in genomic DNA. The GK gene is expressed most in human liver with three transcript sizes of 1.85, 2.7, and 3.7 kb. Sequence analysis of 1.5 kb of several overlapping liver cDNA clones predicted a protein with approximately 63% similarity to the E. coli and B. subtilis glycerol kinase genes. The liver cDNA clones have sequence identity with four genomic exons and the 3' untranslated region from an Xp21.3 cosmid thus indicating that this is the expressed GK gene which when deleted in patients gives rises to GK deficiency. PMID- 8499899 TI - Human olfactory marker protein maps close to tyrosinase and is a candidate gene for Usher syndrome type I. AB - Olfactory marker protein (OMP) shows olfactory neuron-specific expression in rodents. We recently reported tight linkage on mouse chromosome 7 of OMP to the shaker-1 deafness mutant, between the tyrosinase and globin loci. Here we isolate and map the human homologue. Our results show that OMP maps immediately centromeric to tyrosinase on the long arm of human chromosome 11. Genetic linkage to this region has recently been established for Usher Syndrome Type I, an autosomal recessive blindness and deafness disorder and a putative homologue of the shaker-1 mutant. OMP is thus a candidate gene for both congenital deafness defects. PMID- 8499900 TI - Assignment of a gene locus involved in craniosynostosis to chromosome 5qter. AB - Craniosynostosis, the abnormal development of the calvarial sutures, occurs as an autosomal dominant trait in many clinically distinct syndromes. We performed linkage analysis of a provisionally novel type of autosomal dominant craniosynostosis in a large three generational family. Linkage was established between the craniosynostotic locus and D5S211, a locus defined by the short tandem repeat polymorphism (STRP) marker Mfd 154 in distal 5q. The maximum LOD score, Zmax, was 4.8 at a recombination fraction of zero. No significant linkage was found with markers located 30 cM and more proximal to D5S211. The findings assign the craniosynostotic locus in this family to a telomeric region in the long arm of chromosome 5. Linkage analysis with Mfd 154 in other autosomal dominant craniosynostotic syndromes should reveal whether these disorders are caused by mutations of genes at the same or at different loci. PMID- 8499901 TI - A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein. AB - Three cDNA transcripts corresponding to complementation group C of Fanconi anemia (FA) were recently cloned. We confirm that the correct reading frame was reported and that a protein of an apparent molecular mass of 60 kDa is translated. A T-to C transition at base 1,661 in the open reading frame is the only change found to date in the FA(C) cell line, resulting in a codon substitution from leucine554 to proline. Using site directed in vitro mutagenesis, we demonstrate that this mutation completely abolishes the activity of the FACC protein as analyzed by functional complementation assay. The physiological significance of this mutation is thus confirmed. PMID- 8499902 TI - Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22. AB - Genetic linkage analysis has been instrumental in mapping the gene for X-linked agammaglobulinemia (XLA) to the proximal long arm of the human X chromosome, to Xq22. Due to the relative rarity of this disease the localization of the gene within Xq22 has remained imprecise. We have investigated twenty-nine families affected by XLA and have found no recombinants with the DXS178 locus in over 30 informative meioses. DXS178 is now the most reliable and informative locus for use in pre-natal diagnosis and carrier detection of XLA. In addition, we have identified new closely linked proximal and distal flanking markers for XLA, DXS442 and DXS101, respectively. These loci are separated by 2cM, considerably reducing the extent of DNA within which the XLA locus can be contained. This will open up the way for more directed positional cloning efforts for the isolation of the XLA gene. PMID- 8499903 TI - Multiplex PCR of three dinucleotide repeats in the Prader-Willi/Angelman critical region (15q11-q13): molecular diagnosis and mechanism of uniparental disomy. AB - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation disorders caused by a deficiency of paternal (PWS) or maternal (AS) contributions for chromosome 15 by either deletion or uniparental disomy (UPD). To further study the molecular mechanisms involved in these disorders and to improve molecular diagnostic methods, we have isolated three dinucleotide repeat markers in the PWS/AS critical region. An Alu-CA PCR method was used to isolate CA-repeat markers directly from yeast artificial chromosome (YAC) clones identified by probes IR4-3R (D15S11), LS6-1 (D15S113), and GABAA receptor B3 (GABRB3). Three markers with 6-11 alleles and 73-83% heterozygosities were identified and analyzed by multiplex PCR. Gene-centromere mapping was performed on a panel of ovarian teratomas of known meiotic origin, and showed the most proximal marker, IR4-3R, to be 13 cM (95% confidence limits: 7-19 cM) from the centromere of chromosome 15. Molecular diagnostic studies were performed on 20 PWS and 9 AS patients. In 17 patients with deletions, the parental origin of deletion was determined. Ten PWS patients were shown to have maternal heterodisomy. Since these markers are only 13 cM from the centromere, heterodisomy indicates that maternal meiosis I nondisjunction is involved in the origin of UPD. In contrast, two paternal disomy cases of AS showed isodisomy for all markers tested along the length of chromosome 15. This suggests a paternal meiosis II nondisjunction event (without crossing over) or, more likely, monosomic conception (due to maternal nondisjunction) followed by chromosome duplication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499904 TI - High rate of multilocus deletion in a human tumor cell line. AB - The nature of recessive mutations at the autosomal locus encoding the purine salvage enzyme adenine phosphoribosyl transferase (APRT) was analyzed in a highly malignant human tumor cell line (the colorectal carcinoma line SW620). Mutant strains resistant to the purine analog 8-azaadenine were obtained in two steps. The first step selection for partial drug resistance produced strains hemizygous for APRT as a result of high frequency loss of one allele. In the second step selection, low frequency base substitutions, small deletions, or insertions produced complete azaadenine resistance. Luria-Delbruck fluctuation analysis of each step of this process indicated that the rate of mutation resulting from allele loss was over 100-fold greater than the rate of mutation resulting from base substitution. There was no reproducible difference in the rate of loss of either of the two APRT alleles even though one maps to a rearranged chromosome. Similarly base substitution rates for the two alleles were not significantly different. Polymorphic loci surrounding APRT on chromosome 16 band q24 were lost together with the selected gene in all isolates while polymorphic loci on the short arm of the chromosome were retained. Thus the high frequency loss of APRT in SW620 appears to be the result of multilocus deletions. SW620 derivatives behaving as heterozygotes were also obtained in the first step selections, but these constituted only 5% of isolates. PMID- 8499905 TI - Genomic position influences spontaneous mutagenesis of an integrated retroviral vector containing the hprt cDNA as target for mutagenesis. AB - We have used five isogenic human lymphoblastoid cell lines each containing a retroviral vector at a different position in the genome to assess the influence of these positions on spontaneous mutagenesis. The vector contains the hamster hprt cDNA and the neo gene, both genes are transcribed from the retroviral LTR promoter. The rates of mutation leading to a HPRT- phenotype during growth in non selective medium differed up to 60-fold in the five retroviral integrates, ranging from 5.9 x 10(-6) to 3.5 x 10(-4) mutations per cell generation. From each of the cell lines approximately 20 independent mutants were analyzed by Southern blot analysis. In two cell lines all mutations were caused by inactivation of the LTR promoter (presumably by DNA methylation), whereas in another cell line the estimated rate of this mutation is 1000-fold lower. Another important class of mutation is homologous recombination between the LTRs. This accounts for at least half of the mutants in the other three cell lines. Mutants carrying deletions or point mutations form a minor fraction of the mutant distribution. Mutations confined to the hprt cDNA sequences only were studied by selecting HPRT- mutants in the presence of G418. Even for this subset of mutations the rates can vary at least 10-fold between the different genomic positions, ranging from 4.2 x 10(-7) to 5.1 x 10(-6). We conclude therefore that mutations leading to a HPRT- phenotype are quantitatively as well as qualitatively different in the studied cell lines. This suggests that spontaneous mutagenesis in a gene is dependent on its position in the genome. PMID- 8499906 TI - Low-copy-number repeat sequences flank the DiGeorge/velo-cardio-facial syndrome loci at 22q11. AB - DiGeorge syndrome and velo-cardio-facial syndrome are associated with deletions within 22q11. In attempting to refine the shortest region of overlap for these syndromes we have employed fluorescence in situ hybridisation. The results obtained for some probes indicate the presence of low-copy-number repeat families dispersed through proximal 22q. Several primate species have been examined for the presence or absence of two sequences mapping to pter-22q11. The results suggest a relatively recent evolutionary origin for these sequences and the loss of one sequence during the course of primate evolution. PMID- 8499907 TI - The identification of a third fragile site, FRAXF, in Xq27--q28 distal to both FRAXA and FRAXE. AB - FRAXA is unique amongst fragile sites in that it is intimately involved with a specific clinical phenotype, the fragile X syndrome. Whilst the majority of fragile X individuals have been found to have a characteristic mutation in the FMR1 gene, a small proportion of individuals exhibiting fragility have no such mutation. Investigation of the site of chromosome fragility in these FMR1 mutation negative, fragile X site positive individuals, has identified a second site of fragility, FRAXE. However, the presence of FRAXE has not explained all such cases. Here we describe a fragile X site positive, FMR1 mutation negative family, in which chromosome fragility is not due to the FRAXA or FRAXE but is due to a third site designated FRAXF. Using fluorescent in situ hybridisation (FISH) this site is shown to lie over 1Mb distal to FRAXA. The identification of a third fragile site in this small region of the X chromosome provides an opportunity to extend our studies of the molecular nature of chromosome fragility. PMID- 8499908 TI - Exclusion of the 15q locus as a candidate gene for severe childhood autosomal recessive Duchenne-like muscular dystrophy in Brazilian families. PMID- 8499909 TI - Identification of a 3' acceptor splice site mutation (g2610c) in the acid sphingomyelinase gene of patients with Niemann-Pick disease. PMID- 8499910 TI - A large deletion at the 3' end of the rhodopsin gene in an Italian family with a diffuse form of autosomal dominant retinitis pigmentosa. PMID- 8499911 TI - Cloning of the X-linked glycerol kinase gene. PMID- 8499912 TI - Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue. AB - cDNA clones from a human adult testis cDNA library were isolated and sequenced as part of a programme to produce expressed sequence tags (ESTs). ESTs were used routinely to search DNA and protein sequence databases. One clone (142) showed 60% identity to the Bacillus subtilis glycerol kinase gene at both the DNA and amino acid sequence levels. Analysis of DNA from somatic cell hybrids carrying deleted X chromosomes, has shown that clone 142 detects homologous sequences between Xp21.2-p22.1 (the interval containing the locus responsible for glycerol kinase deficiency--GKD). These sequences are deleted in two patients with GKD. Clone 142 also detects homologous sequences on Xq and at several autosomal loci. The sequences of clone 142 and two further cDNA clones isolated from a human foetal brain cDNA library are presented. PMID- 8499913 TI - The organization and conservation of the human Surfeit gene cluster and its localization telomeric to the c-abl and can proto-oncogenes at chromosome band 9q34.1. AB - The mouse Surfeit locus contains an unusually tight cluster of six housekeeping genes (Surf-1 to -6) which are unrelated by sequence homology. Using a mouse Surfeit locus probe, a 16 kb clone has been isolated which contains the human Surf-1 and Surf-3 genes and regions of the human Surf-2 and Surf-5 genes. The organization and juxtaposition of these human Surfeit locus genes are the same as found in the mouse. Using the human clone as a biotinylated probe for fluorescence in situ hybridization (FISH) we have confirmed the location of the human Surfeit locus to chromosome band 9q34. Metaphase spreads of human chronic myeloid leukemic cells containing the t(9;22)(q34;q11) translocation involving The c-abl gene at 9q34.1 an acute nonlymphocytic leukemic cells containing the t(6;9)(q34;p23) translocation involving the can gene at 9q34.1 were analyzed by FISH using the human Surfeit clone as a probe. These analyses locate the human Surfeit locus telomeric to the c-abl and can genes at chromosome band 9q34.1. PMID- 8499914 TI - Point mutation in a 3' flanking sequence of the alpha-1-antitrypsin gene associated with chronic respiratory disease occurs in a regulatory sequence. AB - A point mutation in the 3' flanking sequence of the alpha-1-antitrypsin gene is associated with chronic respiratory disease. This study demonstrates that the mutation occurs in a motif that binds a nuclear factor. A direct consequence of the mutation is the loss of specific binding. Functional studies with constructs containing this region downstream of a reporter gene in the sense orientation demonstrated that the wild type sequence increased expression compared with control promoter plasmid and there was a significant reduction in expression by the mutant sequence. These effects were demonstrated in three distinct cell lines suggesting an ubiquitous rather than a tissue-specific effect. However, transacting factors may influence the response in different tissues. The mutation does not appear to affect basal expression of the protein as the plasma concentration of alpha-1-antitrypsin is normal in individuals who carry the mutation. However, the binding and functional studies suggest that it may reduce the three- to four-fold rise in plasma alpha-1-antitrypsin concentration that occurs during inflammation. PMID- 8499915 TI - Rapid physical mapping of YAC inserts by random integration of I-Sce I sites. AB - We have developed a novel strategy, based on the random insertion by homologous recombination of artificial I-Sce I sites within mammalian repetitive DNA sequences, which should greatly facilitate the high resolution physical mapping of large DNA fragments cloned in YAC. A set of transgenic yeast strains containing appropriately spaced I-Sce I sites within the YAC insert defines a series of nested physical intervals against which new genes, clones or DNA fragments can be mapped by simple hybridisation. Sequential hybridisation using such a series of nested YAC fragments as probes can also allow the rapid sorting of phage or cosmid libraries into contigs. This approach, which has been applied to a YAC containing a 460 kb insert from the mouse X chromosome, may also have applications for the restriction mapping of large genomic segments, mapping of exons and the search for homologous genes. PMID- 8499916 TI - The carboxyl-terminal half of type VII collagen, including the non-collagenous NC 2 domain and intron/exon organization of the corresponding region of the COL7A1 gene. AB - The COL7A1 gene, which encodes type VII collagen, has been implicated as a candidate gene for dominantly and recessively inherited forms of dystrophic epidermolysis bullosa. In this study, hamster and human cDNA clones, which encode the previously uncharacterized carboxyl-terminal portion of type VII collagen, have been isolated and characterized. The previously uncharacterized carboxyl terminal NC-2 non-collagenous domain is shown to be comprised of 161 amino acids in humans, 170 amino acids in hamster and to contain 8 conserved cysteines in each species. The 6 most carboxyl-terminal cysteines are contained in a conserved motif similar to domains found in Kunitz protease inhibitors, and most closely resembling a similar motif found in the carboxyl-terminal globular domain of the alpha 3 chain of type VI collagen. Also contained in the highly acidic NC-2 domain are a number of potential sites for phosphorylation by casein kinases. Human genomic clones containing 24 exons of COL7A1 were isolated and characterized. The NC-2 domain is encoded by 7 of these exons, which include a junctional exon encoding the end of the collagenous region and the beginning of the NC-2 domain and a final exon encoding the end of the NC-2 domain and 333 bp of 3' untranslated sequences. Comparison of hamster and human sequences shows the region surrounding the junction of the collagenous and NC-2 domains to be particularly conserved. This region is likely to contain residues involved in the proteolytic removal of the NC-2 domain and cysteines involved in formation of the disulfide linkages which stabilize type VII collagen dimers. PMID- 8499917 TI - Genetic linkage between von Hippel-Lindau disease and three microsatellite polymorphisms refines the localisation of the VHL locus. AB - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25-p26 and presymptomatic diagnosis using linked DNA markers is available. We have previously mapped the VHL disease gene to a 4 cM interval between D3S1250 and D3S18. To increase access to presymptomatic diagnosis and to accelerate progress towards isolating the VHL disease gene we attempted to identify microsatellite DNA markers linked to the disease gene by genetic linkage analysis in 29 families. We found significant linkage between the VHL disease gene and dinucleotide (CA) repeat polymorphisms at D3S1038 (Zmax = 22.24 at theta = 0.01, CI 0.0001-0.06), D3S1110 (Zmax = 11.32 at theta = 0.07, CI 0.03-0.14) and D3S651 (Zmax = 7.73 at theta = 0.04, CI 0.008 0.13). We localised D3S1038 between D3S1250 and D3S601, and mapped D3S1110 and D3S651 centromeric to D3S1250. Multipoint linkage analysis mapped the VHL disease locus between D3S1038 and D3S18 with the maximum likelihood at D3S601. There was no evidence of locus heterogeneity. This study has (i) identified three microsatellite DNA markers in chromosome 3p25 linked to the VHL disease gene and (ii) narrowed the target region for the isolation of the VHL disease gene by positional cloning techniques. These findings will improve the management of families with VHL disease by improving the accuracy and availability of presymptomatic diagnosis using linked DNA markers, and will accelerate progress towards isolating the VHL disease gene. PMID- 8499918 TI - Allele non-amplification: a source of confusion in linkage studies employing microsatellite polymorphisms. AB - Microsatellite polymorphisms provide highly informative readily detectable markers for human linkage studies. This paper reports apparent non-Mendelian inheritance of a dinucleotide repeat polymorphism due to allele non amplification. The previously hidden allele was revealed and Mendelian inheritance restored when a new CA strand primer was used for amplification. Sequencing of the hidden allele identified a single base substitution at the 3' most position of the binding site for the original CA strand primer. Allele non amplification is a potential source of confusion in linkage studies employing polymorphisms detected by the polymerase chain reaction. It should be considered whenever apparent non-Mendelian inheritance or non-paternity are encountered. PMID- 8499919 TI - Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians. AB - DNA samples of patients from around the world have been sequenced to precisely define the mutations in the factor IX gene resulting in hemophilia B. This study compares the patterns of independent mutation between 127 Caucasian and 44 non Caucasian patients with hemophilia B. Caucasians and non-Caucasians are found to have similar patterns of transitions and transversions (both at CpG and at non CpG sites) as well as insertions, deletions, microdeletions, and complex changes (chi 2 = 2.71, p = 0.922). An analysis of subgroups of transitions and transversions shows similar patterns among Caucasians and non-Caucasians (chi 2 = 2.98, p = 0.83). If the subset of non-Caucasian samples (24) in which the mutation is known to have occurred outside of the United States, Canada, and Europe (UCE) is compared to the Caucasian subset, the above conclusions are unchanged. The invariant nature of this pattern of mutation is most simply compatible with a predominance of endogenous processes or common mutagen exposure rather than mutagen exposure specifically associated with non-Caucasian status or non-Western lifestyle. PMID- 8499920 TI - Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene. AB - The mutation causing myotonic dystrophy (DM) has recently been identified as an unstable CTG trinucleotide repeat located in the 3' untranslated region of a gene encoding for a protein with putative serine-threonine protein kinase activity. In this report we present the genomic sequences of the human and murine DM kinase gene. A comparison of these sequences with each other and with known cDNA sequences from both species, led us to predict a translation initiation codon, as well as determine the organization of the DM kinase gene. Several polymorphisms within the human DM kinase gene have been identified, and PCR assays to detect two of these are described. The complete sequence and characterization of the structure of the DM kinase gene, as well as the identification of novel polymorphisms within the gene, represent an important step in a further understanding of the genetics of myotonic dystrophy and the molecular biology of the gene. PMID- 8499921 TI - The isolation of cDNAs within the Huntington disease region by hybridisation of yeast artificial chromosomes to a cDNA library. AB - Flanking recombination events have defined the Huntington Disease gene candidate region to between D4S10 and D4S98, about 2.2Mb. Because of the large size of the candidate region and the likely large number of genes within it we decided to screen cDNA libraries with probes generated from whole Yeast Artificial Chromosomes (YACs) containing parts of this region. We have thus far used 4 YACs ranging in size from 180kb to 600kb covering 880kb and have isolate 13 cDNA clones, 7 of which are unique. Three of the 13 clones contain parts of the 3' untranslated region of the alpha-adducin gene. One YAC of 600kb could not be purified from two yeast chromosomes, therefore this YAC probe had a net complexity of 1.8Mb. Even so this probe identified a cDNA from the HD candidate region indicating that very large YACs may be used as probes. PMID- 8499922 TI - Identification of two point mutations and a one base deletion in exon 19 of the dystrophin gene by heteroduplex formation. AB - Two thirds of the Duchenne muscular dystrophy population have either gene deletions or duplications. The nondeletion/duplication cases are most likely the result of point mutations or small deletions and duplications that cannot be easily identified by current strategies. The major obstacle in identifying small mutations is due to the large size of the dystrophin gene. We selectively screened 5 DMD exons containing CpG dinucleotides in 110 DMD patients without detectable deletions or duplications. Nonsenses mutations are frequently due to a C- to -T transition within a CG dinucleotide pair. To screen for the nonsense mutations, we used the heteroduplex method. Utilizing this approach, we identified 2 different nonsense mutations and a single base deletion all occurring in exon 19. This is the first report of a clustering of small mutations in the dystrophin gene. PMID- 8499923 TI - No mutation in codon 713 of the amyloid precursor gene in schizophrenic patients. PMID- 8499924 TI - Molecular characterization of the H319Q galactosemia mutation. PMID- 8499925 TI - DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency. PMID- 8499926 TI - Reassignment of pEFD70.3 (D18S23) to human chromosome band 21q22.2 (D21S412) by physical mapping. PMID- 8499927 TI - pMCT108.2 is a chimaeric clone which physically maps to human chromosome bands 9q33 (D9S203) and 18q21.1 (D18S24). PMID- 8499928 TI - Dinucleotide repeat polymorphism at locus D19S207, close to the myotonic dystrophy (DM) gene. PMID- 8499929 TI - Two novel sequence polymorphisms of the human carnitine palmitoyltransferase II (CPT1) gene. PMID- 8499930 TI - A centromeric microsatellite probe on chromosome 3: LIB 9-95ca (D3S1338). PMID- 8499931 TI - Dinucleotide repeat polymorphism at the D22S268 locus. PMID- 8499932 TI - Microsatellite repeat polymorphism at the D13S197 locus. PMID- 8499933 TI - A new polymorphic probe on chromosome 22q (XD6) (D22S313). PMID- 8499934 TI - Nutritional ergogenic aids: caffeine. PMID- 8499935 TI - Chromium picolinate is an efficacious and safe supplement. PMID- 8499936 TI - Prevalence of eating disorders in elite female athletes. AB - This study examined the prevalence of eating disorders (ED) and the possible difference between ED symptoms and true ED by using questionnaires as compared with an interview and clinical evaluation in Norwegian elite female athletes (n = 522) from 35 sports and nonathletic controls (n = 448). In addition to the 117 athletes classified as "at risk" to develop ED, 90 subjects were randomly chosen, comprising 30 athletic controls, 30 at-risk nonathletes, and 30 nonathletic controls. All were interviewed and clinically examined. A significantly higher number of athletes (18%) than controls (5%) were found to actually suffer from ED, particularly athletes competing in sports in which leanness or a specific weight were considered important. When results from the screening study were compared to those from the interviews and clinical examinations, a significant underreporting of ED among athletes was demonstrated. The athletes also reported the use of other pathogenic methods in the screening study compared to what they reported in the interview. Nonathletes more correctly reported the use of pathogenic methods but overreported the prevalence of ED. Thus the issue of using questionnaires alone or in combination with personal interview/clinical examination merits further investigation. PMID- 8499937 TI - Differences in the effects of carbohydrate food form on endurance performance to exhaustion. AB - This investigation examined the metabolic and performance effects of ingesting solid compared to slurried carbohydrate food (bananas) between two prolonged exhaustive exercise bouts. Eight highly trained male triathletes performed four exhaustive endurance tests (ET), each separated by at least 2 weeks. Each ET consisted of a 90-min run followed by 90 min of cycling, both at 70% VO2max. Workloads were then gradually increased on the cycle, and subjects continued to cycle until exhausted. They then rested for 20 min and ingested one of the following: an artificially sweetened placebo drink (P), slurried bananas (SL), or solid bananas (SO). Bananas were given in equal portions relative to each subject's body weight. Subjects cycled to exhaustion a second time at 70% of their VO2max, at which point the mean blood glucose concentration for the combined carbohydrate treatments was significantly higher than that from the P treatment. The mean glucose concentration from the SL treatment did not differ significantly from the SO treatment. These data demonstrate that solid bananas are as effective as slurried bananas in maintaining plasma glucose and in enhancing endurance exercise performance. PMID- 8499938 TI - Failure to find increased TEM at rest and during exercise in aerobically trained and resistance trained subjects. AB - This study examined the metabolic response to a 763-kcal mixed meal at rest and during 30 min of exercise at 50% maximal oxygen consumption (VO2max) in 8 aerobically trained (AT), 8 resistance trained (RT), and 8 untrained (UT) subjects. Oxygen consumption (VO2) was measured minute by minute during 30 min of exercise by indirect calorimetry on 2 nonconsecutive days (postabsorptive exercise, PA; and postprandial exercise, PP). Total VO2 consumed and total caloric expenditure during the PA and PP conditions were similar for the three groups, indicating that prior food intake did not affect energy expenditure during exercise. Consequently, TEM during exercise did not differ significantly among the groups. Respiratory exchange ratio (R) differed significantly only during the PA condition, with the AT group exhibiting significantly lower R values compared to the RT group, and significantly lower R values compared to the UT group. These data suggest that the consumption of a meal 30 min prior to exercise does not increase TEM during exercise in AT, RT, and UT subjects. PMID- 8499939 TI - The effects of intermittent liquid meal feeding on selected hormones and substrates during intense weight training. AB - This study examined the effects of feeding a liquid meal during weight training on selected hormones and substrates. Ten male subjects were given a meal (MW) or nonnutritive placebo (W) before and intermittently during a 2-hr weight training session, and a meal before and intermittently during 2 hours of rest (M). Serum insulin increased from 12.2 +/- 1.2 and 11.2 +/- 1.3 before feeding to 37.2 +/- 4.8 and 45.0 +/- 5.0 mU.ml-1 during exercise in MW and M, respectively, and remained elevated for 120 min. Insulin remained at resting levels in W throughout the experiment. Glucose increased from 5.20 +/- 0.16 and 4.82 +/- 0.20 before feeding to 6.23 +/- 0.30 and 6.0 +/- 0.36 mmol.l-1 at the beginning of exercise in MW and M. Glucose declined during the first 15 min of exercise in MW and M but remained at or above resting levels for 120 min in MW. Lactate increased above 5.9 mmol.l-1 in W and MW during exercise. Glucagon remained unchanged in all groups. Perceived exertion during exercise was 8.5 +/- 0.16 for MW and 8.3 +/- 0.18 for W. Feeding a liquid meal before and during weight training exercise can increase serum insulin and maintain blood glucose for a prolonged period. PMID- 8499940 TI - Diet and exercise strategies of a world-class bodybuilder. AB - This study presents the diet and exercise strategies of a world-class body builder during an 8-week precompetition period. Weighed food records were kept daily, and body fat, resting metabolic rate (RMR), VO2max, blood lipids, and liver enzymes were measured. Two hrs of aerobic exercise and 3 hrs of weight training were done daily 6 days/week. Mean energy intake was 4,952 kcal/day (54 kcal/kg) and included 1,278 kcal/day from medium-chain triglycerides (MCT). Diet without MCT provided 76% of energy from carbohydrate, 19% from protein (1.9 g protein/kg), and 5% from fat. Micro-nutrients were consumed at > or = 100% of the RDA, except for zinc and calcium, without supplementation. Mean RMR was 2,098 kcal/day and represented 43% of energy intake. VO2max was 53 ml.kg-1.min-1. Underwater weighing showed that body fat decreased from 9% to 7%. Blood lipids were normal, but two liver enzymes were elevated (alanine and aspartate aminotransferase). This world-class bodybuilder achieved body fat goals by following a nutrient dense, high energy, high carbohydrate diet and an exercise program that emphasized both aerobic and anaerobic metabolism. PMID- 8499941 TI - Diet and weight changes of female bodybuilders before and after competition. AB - This study assessed nutritional and body weight patterns in 6 female bodybuilders approximately a month before and after a competition. The women kept dietary and body weight records and two of them also agreed to collect morning urine samples to provide information about their menstrual cycle. All women lost weight before and gained weight after competition. Energy intake was modestly restricted and the subjects consumed a moderate-protein, low-fat, high-carbohydrate diet just prior to competition. Energy intake doubled, and total grams of fat increased approximately tenfold just after competition. Urinary data indicated that the cycle following competition was prolonged, with reduced reproductive hormone concentrations. In summary, the women practiced extreme dietary control while preparing for a competition but followed the event with a higher energy and fat intake. These changes in diet and body weight may contribute to the disturbances previously observed in the menstrual cycle of these athletes. PMID- 8499942 TI - The last shall be first. PMID- 8499943 TI - Anchored reference loci for comparative genome mapping in mammals. AB - Recent advances in gene mapping technologies have led to increased emphasis in developing representative genetic maps for several species, particularly domestic plants and animals. These maps are being compiled with two distinct goals: to provide a resource for genetic analysis, and to help dissect the evolution of genome organization by comparing linkage relationships of homologous genes. We propose here a list of 321 reference anchor loci suitable for comparative gene mapping in mammals and other vertebrate classes. We selected cloned mouse and human functional genes spaced an average of 5-10 centiMorgans throughout their respective genomes. We also attempted to include loci that are evolutionarily conserved and represented in comparative gene maps in other mammalian orders, particularly cattle and the domestic cat. We believe that the map may provide the basis for a unified approach to comparative analysis of mammalian species genomes. PMID- 8499944 TI - Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. AB - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized by progressive and variable involvement of tissues predominantly derived from the neural crest and a predisposition toward malignancies. The NF1 gene encodes neurofibromin, a GTPase-activating protein containing a GAP-related domain (NF1-GRD) that is capable of down-regulating ras by stimulating its intrinsic GTPase activity. We report a homozygous deletion of most of NF1 in one of eight malignant melanoma cell lines leading to loss of detectable mRNA and protein, as well as the apparent absence of protein and mRNA in another melanoma. This data suggests that NF1 can function as a tumour suppressor gene in the development or progression of malignant melanoma. PMID- 8499945 TI - Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. AB - Individuals with neurofibromatosis type 1 (NF1) have an increased risk of developing benign and malignant tumours. The NF1 gene is thought to be a tumour suppressor gene, yet no direct proof at the molecular level exists to support this hypothesis. Here we describe a neurofibrosarcoma from a patient with NF1 with loss of heterozygosity for all chromosome 17 polymorphisms tested. On the remaining chromosome 17 homologue, a 200 kilobase (kb) tumour specific deletion of NF1 was demonstrated. This is the first example of a homozygous inactivation of NF1 at the molecular level in a malignant tumour from an NF1 patient and the results strongly support the tumour suppressor gene hypothesis for this disease. PMID- 8499946 TI - A major susceptibility locus to murine lung carcinogenesis maps on chromosome 6. AB - Lung tumours represent a major cause of death in humans, and although smoking represents the main pathogenetic factor, inheritance also plays a part. However, the identification of possible predisposing genetic factors is difficult, because of their low penetrance. We took advantage of murine strains that are genetically susceptible or resistant to lung tumour development, to map murine genes associated with susceptibility to lung carcinogenesis. An F2 population of urethan-treated A/J x C3H/He mice was scored with 83 genetic markers. A chromosome 6 distal region, spanning mice was scored with 83 genetic markers. A chromosome 6 distal region, spanning 35 centiMorgans, contained a major lung tumour susceptibility locus. No other chromosomal region was significantly associated with lung tumour development. PMID- 8499947 TI - Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. AB - We have conducted a detailed structural analysis of 90 kilobases (kb) of the HLA Class III region from the Bat2 gene at the centromeric end to 23 kb beyond TNF. A single contig of 80 kb was sequenced entirely with a group of four smaller contigs covering 10 kb being only partly sequenced. This region contains four known genes and a novel telomeric potential coding region. The genes are bracketed by long, dense clusters of Alu repeats belonging to all the major families. At least six new families of MER repeats and one pseudogene are intercalated within and between the Alu clusters. The most telomeric 3.8 kb contains three potential exons, one of which bears strong homology to the ankyrin domain of the DNA binding factors NF kappa B and I kappa B. PMID- 8499948 TI - Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age. AB - The study of DNA polymorphisms has permitted the determination of the parental and meiotic origin of the supernumerary chromosome 21 in families with free trisomy 21. Chromosomal segregation errors in somatic cells during mitosis were recognized after analysis of DNA markers in the pericentromeric region and (in order to identify recombination events) along the long arm of chromosome 21. Mitotic errors accounted for about 4.5% (11 of 238) of free trisomy 21 cases examined. The mean maternal age of mitotic errors was 28.5 years and there was no association with advanced maternal age. There was no preference in the parental origin of the duplicated chromosome 21. The 43 maternal meiosis II errors in this study had a mean maternal age of 34.1 years-the highest mean maternal age of all categories of chromosomal segregation errors. PMID- 8499949 TI - Multiple self-healing squamous epitheliomata (ESS1) mapped to chromosome 9q22-q31 in families with common ancestry. AB - A gene (ESS1) predisposing to the development of multiple invasive but self healing skin tumours (squamous cell epitheliomata) is tightly linked to the polymorphic DNA marker D9S53 (9q31) with a maximum lod score of 9.02 at a recombination fraction of 0.03. Multipoint linkage analysis demonstrates that the disease locus is most likely to lie between D9S58 (9q22.3-31) and ASSP3 (9q11 q22). Comparison of markers associated with ESS1 in independently ascertained families suggests a common origin of the disease and defines the location of ESS1. Haplotype studies indicate that the disease locus is most likely to lie between D9S29 (9q31) and D9S1 (9q22.1-q22.2). PMID- 8499950 TI - X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. AB - During mammalian development, one of the two X chromosomes in female embryos is randomly inactivated in the somatic cell in order to achieve gene dosage compensation. But is X inactivation established simultaneously or is it accomplished over time in a lineage-dependent fashion? We have examined this question in mouse embryos carrying an X-linked lacZ transgene. This transgene is subject to inactivation and the loss of beta-galactosidase activity provides a direct indication of X inactivation in individual cells. We find that X inactivation proceeds with different schedules in different somatic tissues, and the notochord, the heart, cranial mesoderm and the hindgut are among the last tissues to undergo X inactivation. PMID- 8499951 TI - Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation. AB - Haemophilia B Leyden is characterized by low childhood levels of factor IX which gradually increase after puberty, eventually resulting in a return to health. The disease is the result of single nucleotide substitutions within a 40 bp region encompassing the major transcriptional start site. We have characterized transcription factor binding sites within the factor IX promoter. Five sites were identified and a Leyden mutation at nucleotide -5 was shown to interfere with the binding of proteins to one of three newly identified sites. The correlation between the post-pubertal recovery of these mutants and the induction of the transcription factor DBP led us to the discovery of a synergistic interaction between DBP and C/EBP responsible for the recovery of normal transcriptional activity of the -5 mutant promoter and may play a role in the resolution of other Leyden mutants. PMID- 8499952 TI - Towards gene therapy for haemophilia B using primary human keratinocytes. AB - Haemophilia B might be permanently cured by gene therapy--the introduction of a correct copy of the factor IX gene into the somatic cells of a patient. Here, we have introduced a recombinant human factor IX cDNA into primary human keratinocytes by means of a defective retroviral vector. In tissue culture, transduced keratinocytes were found to secrete biologically active factor IX and after transplantation of these cells into nude mice, human factor IX was detected in the bloodstream in small quantities for one week. This is the first demonstration of a therapeutic protein reaching the bloodstream from transduced primary keratinocytes. This may have implications for the treatment of haemophilia B and other disorders. PMID- 8499953 TI - Lorenzo goes to Hollywood. PMID- 8499954 TI - Marfan gene dissected. PMID- 8499955 TI - Clinical management of the menopausal woman. AB - It is estimated that in the future, in industrialized countries, physicians will spend the majority of their time treating women over 65. In terms of the individual female patient, women may expect to live one-third of their lives after menopause. The hot flashes that are experienced by most postmenopausal women, in many cases for 5 years or more, are the most common indications for estrogen replacement therapy, and there are studies showing lower levels of estradiol and estrone in women severely afflicted than in those who are not. A long-range indication for estrogen replacement therapy is osteoporosis, which in the U.S. causes 700,000 bone fractures annually, of which 300,000 are femoral neck (hip) fractures. Another common fracture in this group is vertebral fracture, which is six to ten times as common in postmenopausal women as it is in men of middle or old age. Another condition thought by a majority of researchers to benefit from estrogen replacement therapy is cardiovascular disease. In fact, it is well demonstrated that there is significant reduction of cardiovascular risk in healthy users and in women with other risk factors. Atrophy of mucosal surfaces of the genitourinary tract is treated both by systemic administration of estrogen and by topical administration of estrogen-containing cream. Certain conditions, grouped together as the "menopausal syndrome," may also be indications for estrogen replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499956 TI - Hormone replacement therapy and cardiovascular disease. AB - Cardiovascular disease is the chief cause of death among women in industrialized countries. Even breast cancer deaths, at 100/100,000 annually, are only 20% those from cardiovascular disease. However, the research effort in the area of cardiovascular disease among postmenopausal women is far smaller than those for osteoporosis or cancer. In postmenopausal women, the risk of cardiovascular disease rises dramatically, and among the elderly exceeds that of males. Although there is overwhelming evidence that HRT reduces the incidence, many physicians assume that it may cause hypertension and thrombosis, perhaps under the mistaken impression that HRT has the same side effects as the first generation of steroid contraceptives. A number of studies have demonstrated that cardiovascular mortality of postmenopausal women on HRT decreases by approximately one-half. The main epidemiologic evidence for this is a series of case-control and prospective (cohort) studies. Some 20 studies over the last 15 years could be briefly summarized by saying that approximately one third found cardiovascular risk among HRT users to be reduced by > 50% compared with non-users; one third found risk reductions < 50%; and one third found increased risks. HRT appears to affect a large number of risk factors associated with cardiovascular disease; but many formerly thought to be of significance have little clinical relevance, whereas some factors, such as peripheral vascular resistance and certain prostanoids, are apparently much benefited. The benefits of HRT for lipid factors (HDL cholesterol, LDL-cholesterol, etc.) are well known, but recent evidence indicates that changes in these lipids account for only 20-25% of the cardiovascular benefits of HRT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499958 TI - Clinical experience with Systen, a new transdermal form of hormone replacement therapy. AB - Transdermal therapeutic systems (TTSs) represent an important advance in the evolution of hormonal replacement therapy. Not only do these formulations offer an advantage over oral dosing forms with respect to various pharmacokinetic characteristics, but also their lack of first-pass hepatic metabolism results in a highly favorable safety profile. Two multicenter studies have recently evaluated the efficacy, safety and patient acceptability of a new estradiol containing TTX, Systen. Systen is a thin, transparent patch that contains 3.2 mg micronized 17 beta-estradiol within a novel drug delivery system. In Study 1, 196 postmenopausal women were treated continuously or cyclically for 5 months with Systen. About half of the study participants had been switched from another form of ERT. The results showed that Systen was effective and well tolerated, independent of whether it was used continuously or cyclically by "starters" or "switchers." Eighty-seven percent of the subjects rated Systen as very comfortable to wear. In Study 2, 549 postmenopausal women were randomized to six cycles of treatment with either Systen or an older TTS, Estraderm. Once again, both patches were effective and well tolerated. However, Systen was associated with fewer adverse skin reactions and was significantly superior to Estraderm with respect to patch adhesiveness and patient assessment of treatment convenience. These differences between the two patches reflect progressive refinements in TTS technology. PMID- 8499957 TI - Oral versus transdermal hormone replacement therapy. AB - Loss of ovarian function at the menopause results in an increased risk for cardiovascular disease and osteoporosis. Hormone replacement therapy (HRT) in postmenopausal women may reduce or remove this increased risk. The high hepatic bolus seen with oral steroid administration, which may produce unwanted metabolic effects, is avoided by transdermal administration. We studied the metabolic effects of transdermal HRT in comparison with oral HRT or no treatment in 96 healthy postmenopausal women over 3 years. Treatment consisted of either continuous oral conjugated equine estrogens, 0.625 mg daily, with sequential oral dl-norgestrel, 0.15 mg daily, for 12 days per month or continuous transdermal estradiol-17 beta, 0.05 mg daily, with sequential transdermal norethindrone acetate, 0.25 mg daily, for 14 days per month. We measured bone biochemistry and density, serum lipids, lipoproteins and apolipoproteins, and glucose, insulin, and C-peptide concentrations following an intravenous glucose bolus. Minimal modelling analyses provided measures of glucose and insulin kinetics. Both HRT regimens were effective in preventing bone loss, and produced generally favourable lipid and lipoprotein changes. Progestin addition prevented increases in HDL2 cholesterol, but lowered triglycerides. Transdermal estrogen lowered triglycerides, whereas oral estrogen increased them. Furthermore, oral HRT resulted in a deterioration in glucose tolerance and an overall increase in insulin secretion. Transdermal HRT appears at least as effective as oral HRT in preventing postmenopausal osteoporosis, and produces as good, if not better, changes in metabolic risk markers for cardiovascular disease. PMID- 8499959 TI - Prevention and treatment of osteoporosis with hormone replacement therapy. AB - Osteoporosis is characterized by decreased bone mass and increased susceptibility to fractures. The clinical consequences of osteoporosis are fracture, most commonly seen at the wrist, the spine and the hip. The prevalence of osteoporotic fracture is extremely high, with almost 50 percent of 70-year-old women having had at least one osteoporotic fracture. The prevalence in men is lower but may constitute a larger problem than expected. Osteoporotic fracture is therefore a significant cause of morbidity and mortality and represents a major problem of health care. Bone is the site of substantial metabolic exchanges, with bone resorption and formation continuing throughout life. The turnover processes are carried out by osteoclasts and osteoblasts in specialized cellular units. After cessation of growth, the skeleton probably consolidates to reach the peak bone mass at the age of 35-40 years. The relatively slow subsequent age-related bone loss occurs in both men and women, but women are additionally exposed to accelerated bone losses after the menopause. Oestrogen deficiency is the dominating pathogenetic factor for osteoporosis in women and is the drug of choice for prevention and treatment. Today it is established that hormone replacement therapy (HRT), using estrogen alone or estrogen plus a progestogen, can prevent osteoporosis in postmenopausal women. The greatest benefit from HRT is obtained if instituted shortly after menopause. However, the literature contains clear evidence that HRT prevents the bone loss in all stages of the postmenopausal life. A recent study of hormone replacement therapy of women with symptomatic osteoporosis has furthermore demonstrated that the incidence of fractures was significantly reduced during therapy. PMID- 8499960 TI - Kinetics and pharmacology of estrogens in pre- and postmenopausal women. AB - With the approach of the menopause and the cessation of ovarian estrogen production, a number of uncomfortable and/or dangerous conditions may be manifested, and are all indications for estrogen replacement therapy. Various routes of estrogen administration are available--oral, subcutaneous implant, intravaginal, and transdermal--each having advantages and disadvantages. There is also a choice possible among replacement hormones, which include the natural estrogens, such as estradiol and estropipate; synthetic estrogens, for example, ethinyl estradiol and diethylstilbestrol; and conjugated equine estrogens. Depending on both route of administration and choice of hormone, there are great differences demonstrable in kinetics and pharmacologic characteristics, which have not been reflected, however, by highly significant differences in clinical outcome so far. PMID- 8499961 TI - Epidemiology and the menopause: a global overview. AB - There are 470 million women aged 50 years and older living in the world today, in other words, older than the average age of natural menopause throughout recorded history. Only 50 years ago, even in developed countries, the average women did not live to be 50 years of age. The result of this increased survival is that more and more women are living for longer and longer periods of time after their menopause. What are the implications of prolonged life after the menopause? Most of the current interest in the menopause is prompted by its possible relation to chronic diseases, most notably reproductive cancers, osteoporosis, and heart disease. All of these conditions are more common in women after the menopause, and two of them are directly influenced by the use of replacement estrogen. Thus, estrogen replacement reduces the risk of osteoporotic fractures by about 50%, and unopposed estrogen doubles or triples the risk of endometrial cancer. The risk of these conditions without treatment differs in different countries and populations, and consequently the benefit of hormone replacement will differ. The largest potential benefit of estrogen replacement therapy is the prevention of heart disease. In countries with a relatively high risk of heart disease, observational studies suggest that estrogen reduces this risk by 50%. In other areas, where heart disease in women is much less common, the use of estrogen to prevent heart disease in otherwise healthy women is inappropriate given the uncertain relation of long-term estrogen therapy to the risk of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8499962 TI - CEO poll. Who heads up systems integration right now? PMID- 8499963 TI - The race to integrate. Who will be the leaders? AB - Who will integrate care in the health networks emerging across the U.S.? The question is far from academic, as systems integration moves forward dramatically. In our overview, we look at the challenges, conceptual and practical, of partnering. The integration taking place in southeast Michigan "didn't happen overnight," say those involved. But the Blue Cross partnership with two large health systems is transforming health care delivery in that area. The leaders in the Fallon Healthcare Organization in Worcester, MA, say physician direction has been a key to their success. Two Arkansas employers facing the same benefits crisis worked together on costs and ended up redirecting care delivery for employees. Three rural Pennsylvania hospitals faced growing resources issues together and found themselves building a regional alliance. PMID- 8499964 TI - Policy. Paying & delivering: insurers and providers find road to reform is a two way street. PMID- 8499965 TI - Technology's next test. Regional systems laying groundwork for post-reform technology planning. PMID- 8499966 TI - Strategic planning. From the ground up: planting the seeds of network development. AB - It is critical to understand and accept the intense effort and planning needed for successful network development. No model exists that can be immediately implemented successfully. Every organization involved in network development will have to become familiar with the issues, benefits and risks, as well as involve the key stakeholders, which include administration, board and health professional providers from physicians through allied professionals. The outcome of this development can be a very successful, efficient new delivery model that will benefit the users, the payers and the providers. Although difficult and sometimes boring, the methodical and thorough movement through the process of developing a regional community network can greatly enhance outcome. The shared vision of the network should be exciting, and should make participants search for the clear image of what will be developed. All should work jointly as partners to accomplish that vision. Although there may be facilitation and assistance, it will be the providers and stakeholders who will be most affected by the network. It is their commitment, effort, energy and experience that will lead to success. PMID- 8499967 TI - Networking. Southwest Georgia: Columbus partnership targets health status of 10 county area. PMID- 8499968 TI - HIAA President Bill Gradison. Interview by Frank Cerne. PMID- 8499969 TI - Corporate culture: lessening the impact of layoffs on survivors. PMID- 8499970 TI - Data watch. Key features of employee health benefits plans. PMID- 8499971 TI - JCAHO manual sets standards on information management. PMID- 8499972 TI - Low-key, low-cost 'education' for physicians sparks savings. PMID- 8499973 TI - Maryland association strives to improve indicator project. PMID- 8499974 TI - Managed care mergers create 'accountable' health care plans. PMID- 8499975 TI - Can APNs (advance practice nurses) be independent gatekeepers? Yes. PMID- 8499976 TI - Reform and our ability to lead. PMID- 8499977 TI - Urinary tract prostheses and their biocompatibility. PMID- 8499978 TI - A cooling jacket to reduce renal damage during transplantation. AB - There is evidence that warming of the cadaver kidney during transplantation is deleterious to its subsequent function. A simple cooling jacket to delay kidney warming during implantation is described. A controlled study of the temperature rise in 5 porcine kidneys exposed to body temperature showed significant reductions in renal core and cortical temperatures at 60 min from above 30 degrees C to below 13 degrees C when using the jacket. Advantages of this device in practice and some practical points in its use are discussed. PMID- 8499979 TI - Collecting duct carcinoma of the kidney. AB - Collecting duct carcinoma (CDC) is a recently recognised histological variety of renal carcinoma (RC) considered to arise from the epithelium of the collecting ducts. Diagnosis of this entity depends on well defined gross and microscopic criteria and is supported by a characteristic immunostaining pattern. The clinical features of these patients, the natural course of the disease and its response to treatment have not been clearly established. Between 1980 and 1990 we treated 12 patients (median age 43 years, range 16-62) with collecting duct carcinoma of the kidney. In addition to being relatively young, each patient had a strong family history of associated malignancies. Survival was short (median 22 months) and 11 patients presented with locally advanced or metastatic disease. PMID- 8499980 TI - Prophylactic role of extracorporeal shock wave lithotripsy in the management of nephrocalcinosis. AB - Electromagnetic extracorporeal shock wave lithotripsy (ESWL) was performed with a standard Siemens Lithostar on parenchymal calcifications in 10 medullary sponge kidneys in order to evaluate the eventual benefit of preventive lithotripsy. The results of shock wave lithotripsy on precaliceal calcifications were disappointing and have been related to the lack of expansion during shock wave interaction and to the impaired drainage of particles. Three patients also had large impacted ureteric stones and in such cases ESWL remains the treatment of choice. PMID- 8499981 TI - The mobile lithotriptor: an answer for the smaller centre. AB - The mobile lithotriptor is a new method of providing extracorporeal shock wave lithotripsy (ESWL) directly to the smaller urological centres. The unit, containing a Dornier HM4 lithotriptor, has treated 135 patients with a total of 168 treatments in 2 centres in the Oxford region. The overall success rate was 87% with no serious morbidity or mortality. The results compare well with the results from larger centres and the system is cost-effective. We suggest that it is one of the best methods of providing ESWL to the smaller urological centres. PMID- 8499982 TI - Pharmacological options for the treatment of acute ureteric colic. An in vitro experimental study. AB - The effects of opiate and non-steroidal anti-inflammatory agents on the in vitro canine ureter were compared using a new model for the assessment of ureteric pharmacology. A pressure measuring catheter attached to a pressure transducer and pre-calibrated pen recorder was ligated into the lumen of 2.5 cm segments of normal canine ureter. The segments were immersed in an organ bath at physiological pH and temperature and spontaneous contractility was observed in 90% of them. Morphine had a spasmogenic effect on ureteric activity which was unaffected by naloxone. This effect was similar to that of histamine and prostaglandin F2 alpha and was abolished by chlorpheniramine but not by cimetidine. Pethidine produced a transient stimulation followed by inhibition of ureteric activity which was unaffected by naloxone. Both indomethacin and diclofenac produced an abrupt inhibition which was reversible with prostaglandin F2 alpha. These data suggest that pethidine or a non-steroidal anti-inflammatory agent may by virtue of their spasmolytic effects be a superior choice of therapy for the acutely obstructed ureter. PMID- 8499983 TI - Surgical versus endoscopic treatment of non-malignant uretero-ileal anastomotic strictures. AB - The classical treatment of uretero-ileal anastomotic strictures after Bricker uretero-ileostomy is open surgical revision. Recent progress in endourology has provided a number of alternatives. The success rate of these endoscopic techniques is less than the success rate of the open surgical revision. PMID- 8499984 TI - Lumbar epidural blockade for management of pain in interstitial cystitis. AB - Thirteen patients with interstitial cystitis (IC), whose predominant symptom was pelvic or urethral pain, were treated with a series of lumbar epidural local anaesthetic blocks over an 18-month period. Response was evaluated by interview and with voiding diaries and visual analogue scales (VAS) for pain. Of the 55 injections given, immediate pain relief (lasting longer than 24 h) was obtained from 41 (75%). The duration of subsequent pain relief varied considerably, ranging from 2 to 75 days (mean 15.1). Pain relief was accompanied by significant improvement in sleep habit and quality of life. A good correlation was noted between verbally expressed pain and the recorded VAS pain scores. Urinary frequency and average voided volumes were unaffected by treatment. Two patients failed to obtain any relief. Apart from minor transient backache at the injection site, there were no complications from the procedure. Lumbar sympathetic epidural blockade is an excellent means of providing pain relief in interstitial cystitis. PMID- 8499985 TI - Tethered cord syndrome: an unusual cause of adult bladder dysfunction. AB - Tethered cord syndrome is a complication of spinal dysraphism. The tethering of the cord does not permit the normal cranial migration of the conus within the vertebral canal and this results in neural dysfunction due to a traction neuropathy. Although this condition commonly presents in childhood, less severe degrees of tethering may remain asymptomatic until adult life. The clinical features, imaging and management of 5 adults with this condition are reviewed. Both urological and neurosurgical intervention are aimed at preservation of function as, unlike the sensorimotor deficit that commonly complicates this condition, improvement in bladder function is uncommon following cord release. PMID- 8499986 TI - Intralesional alpha interferon therapy in papillary superficial transitional cell carcinoma of the bladder. A pilot study. AB - The tolerability, toxicity and therapeutic efficacy of recombinant interferon alpha-2a (rIFN alpha-2a), administered by intralesional injection, were evaluated in 15 patients with papillary superficial transitional cell carcinoma of the bladder, rIFN alpha-2a was delivered endoscopically in a single weekly dose of 3 x 10(6) IU for 4 weeks (total 12 x 10(6) IU). Transurethral resection of residual tumours was then performed. The response to treatment was assessed according to ultrasonographic, endoscopic and pathological findings. One patient achieved complete remission, 6 partial remission, 6 minor remission and 2 stabilisation of disease. All patients completed the course of treatment. A mild, transient, flu like syndrome was documented after every injection. Immunological findings suggest that the antitumour effects of rIFN alpha 2a are not mediated through the immune system. PMID- 8499987 TI - Interstitial cystitis: correlation with nerve fibres, mast cells and histamine. AB - Interstitial cystitis (IC) is a painful condition in the urinary bladder of unknown aetiology and pathogenesis. To assess the contribution of the nervous system to IC a biopsy was taken from 6 patients with IC and from a control group of 6 patients with non-ulcerative IC. Mast cells were counted and histamine measured in bladder washings from all patients. There were significantly more nerve fibres within the sub-urothelium and detrusor muscle in chronic IC than there were in non-ulcerative IC. The bladder washings from all patients with IC contained mast cells and histamine, while only occasional mast cells and traces of histamine were found in washings from patients with non-ulcerative IC. There was a good correlation between the number of nerve fibres and number of mast cells as well as between the number of nerve fibres and the amount of histamine. PMID- 8499988 TI - Results of treatment with pollen extract (Cernilton N) in chronic prostatitis and prostatodynia. AB - We report the results of a prospective study with the pollen extract, Cernilton N, in a dose of 1 tablet tid for 6 months for the treatment of chronic prostatitis syndrome in 90 patients. The factors documented before and after 3 and 6 months' treatment were digital rectal examination (DRE) of the prostate, uroflowmetry, bacterial studies, leucocyte counts in urine and measurement of complement C3/coeruloplasmin in the seminal fluid. The patients were divided into 2 groups: those without associated complicating factors (CFs) (n = 72) and those with complicating factors, i.e. urethral strictures, prostatic calculi, bladder neck sclerosis (n = 18). In the group without CFs, 56 (78%) had a favorable response; 26 (36%) were cured of their symptoms and signs and 30 (42%) improved significantly with an increase in flow rate, a reduction in leukocyturia in the post-prostate massage urine (VB3) and a decrease in complement C3/coeruloplasmin in the ejaculate. In the patients with CFs only 1 patient showed a response. Complicating factors should be considered in patients who fail to respond to treatment within 3 months. Cernilton N was well tolerated by 97% of patients. PMID- 8499989 TI - Interstitial laser coagulation of the prostate. An experimental study. AB - We describe a percutaneous, low power, interstitial method of controlled coagulation of prostatic tissue by laser light which may prove an alternative or adjunct to existing therapy for benign and malignant prostatic disease. One or more 200-600 micron diameter fibres were implanted within the substance of the elderly male beagle prostate (n = 11) through which Neodymium-Yttrium Aluminium Garnet (Nd-YAG) laser energy could be transmitted. Using longer exposures (400 1500s) and lower powers (1-2W) than used in routine endoscopic laser therapy, well defined areas of coagulative necrosis could be created with little tissue charring or damage to the fibre. For an energy dose of 1000J a lesion approximately 1 cm in diameter resulted at 4 days. Ultrasound scanning methods could detect the fibre(s), the area(s) of coagulation and the healed lesions. Treatments were well tolerated. At 6 weeks the treated areas of canine prostate healed by fibrosis surrounding an area of cystic degeneration. Multiple fibre experiments produced larger volume lesions relevant to more extensive cancer or to the coagulation of benign adenomatous hyperplasia causing outflow symptoms. This technique may prove of value for the treatment of moderate benign enlargement of the prostate and for the destruction of small, focal prostatic tumours. PMID- 8499990 TI - Transrectal ultrasound examination of the prostate: complications and acceptance by patients. AB - Transrectal ultrasound scan (TRUS) of the prostate was performed on 511 patients, 391 of whom also underwent between 1 and 5 transrectal 1.2 mm core biopsies. The infection rate in the whole group was 4.1%; 32% of the patients were given antibiotic prophylaxis with norfloxacin 400 mg twice daily for 1 week and in this group the infection rate was 0.8%. In the remaining patients, who received 400 mg norfloxacin at the time of biopsy and another 400 mg the same evening, the infection rate was 5.6%. The only risk factor identified for post-biopsy infection was steroid medication. Only minor discomfort (or none at all) was reported by 95% of patients during the examination procedure. If TRUS was combined with core biopsy 92% reported either minor or no discomfort. Of 78 patients who experienced both finger-guided fine needle aspiration biopsy and TRUS-guided core biopsy 82% preferred the latter procedure. TRUS and core biopsy proved acceptable to most patients. Antibiotic treatment with 2 tablets of norfloxacin failed to prevent infection. PMID- 8499991 TI - Multiple transrectal ultrasound-guided prostatic biopsies--true morbidity and patient acceptance. AB - Transrectal ultrasound (TRUS) is becoming more widely used as a method of investigating prostatic disease. This study investigated the acceptance of this technique in 89 patients undergoing evaluation for suspected malignant disease. The true morbidity associated with TRUS and TRUS-guided biopsy was evaluated. Serious complications were rare, but minor complications were frequent. Careful counselling is recommended prior to the procedure in order to minimise the patients' anxiety and ensure that if complications do occur they are dealt with swiftly and appropriately. PMID- 8499992 TI - Prevalence and outcome of renal impairment at prostatectomy. AB - Of 382 patients undergoing prostatectomy in Oxford in 1985 the prevalence of renal impairment (defined as plasma urea > 14 mmol/l or plasma creatinine > 200 mumol/l) was 8%; prostatectomy patients had significantly higher plasma ureas than age-matched patients undergoing herniorrhaphy and cholecystectomy in the same hospitals in the same year. A review of the case records of men with renal impairment showed that case history could not predict renal impairment. Although few case notes gave follow-up information, it was evident from the information available that recovery of renal function after prostatectomy did not occur invariably. Renal impairment in men undergoing prostatectomy represents substantial and unrecognised morbidity. PMID- 8499993 TI - Re-evaluation of indications for percutaneous nephrostomy and interventional uroradiological procedures in pelvic malignancy. AB - Twenty-two patients with advanced cancer involving the pelvis were treated by percutaneous uroradiological techniques. Percutaneous nephrostomy was performed for renal failure or urosepsis or before chemotherapy. In 8 patients, ureteric stents were also placed by the antegrade route, across malignant ureteric strictures, following nephrostomy. In another 8 patients, the ureteric obstruction could not be crossed and permanent nephrostomies were required. Fifteen patients were able to achieve a useful life but in the other 7 patients there was no improvement in their quality of life and they all died 1 month after intervention. Percutaneous nephrostomy also contributed to the death of 1 patient. Not all obstructed kidneys require drainage and in patients with disseminated or advanced disease involving the pelvis, the indications for intervention need to be individually assessed. An improvement in laboratory criteria of renal function following intervention does not necessarily result in improvement in quality of life. This retrospective study highlights the difficulty in selection of patients with advanced disease for intervention and previously suggested guidelines for intervention are reviewed. PMID- 8499994 TI - Treatment of stage I testicular tumours. AB - Between 1980 and 1989, 138 patients with stage I carcinoma of the testes were treated and followed up; 81 patients had seminoma and 57 had non-seminomatous tumours. Between January 1980 and December 1983, patients with seminoma were treated by orchiectomy, followed by complementary radiotherapy to aortic and ipsilateral pelvic nodes. Retroperitoneal lymph node dissection (RPLND) was performed in patients with non-seminomatous tumours. After January 1984 the treatment strategy was changed and orchiectomy was followed by a surveillance policy in all histological types. In seminoma patients, 1 of 36 patients (3%) treated with complementary radiotherapy and 5 of 45 (11%) on the surveillance policy relapsed. All achieved a complete response after chemotherapy. In non seminomatous tumours, 3 of 21 patients (14%) treated with complementary lymphadenectomy relapsed, in contrast to 11 of 36 (31%) surveillance policy patients. All patients who relapsed obtained a complete response with chemotherapy. All patients are currently free of disease. There were no differences in survival between both treatment policies. We conclude that a wait and see policy in stage I testicular tumours is feasible and provides the same results as more interventionist practices. PMID- 8499995 TI - Prediction of recovery in antenatally diagnosed hydronephrosis. AB - A series of 335 children with antenatally diagnosed hydronephrosis which persisted after the postnatal period was prospectively assessed. Idiopathic hydronephrosis (85 patients) and pelviureteric junction obstruction (73 patients) were the commonest conditions. All patients with idiopathic hydronephrosis were managed conservatively; 87% have had a complete resolution of hydronephrosis and 13% have remained unaltered. No patient managed conservatively has shown a deterioration in renal function. PMID- 8499996 TI - Fetal ureteric reflux: a follow-up study. AB - The findings in 21 children (17 males) with ureteric reflux diagnosed in the first 3 months of life and likely to have been present antenatally are described; 19 were followed up for between 2 and 8 years. Reflux was grade 3 and bilateral in 13 babies. Radioisotope studies showed evidence of renal parenchymal abnormalities in 45% of non-infected refluxing kidneys. Nonoperative treatment was adopted initially. The reflux disappeared completely in 6 children: evidence that it would do so was apparent within 2 years. Two children developed pelviureteric junction obstruction that was secondary to the dilatation accompanying the reflux. Anti-reflux surgery was performed in 10 children because the degree of reflux and upper urinary tract dilatation were increasing. Operative treatment for fetal ureteric reflux of advanced grades should be considered if there is no improvement after 2 years; gigantic reflux may otherwise ensue. PMID- 8499997 TI - Multifocal bilateral oncocytomas. PMID- 8499998 TI - Nephrogenic adenoma of the ureter complicating genitourinary tuberculosis. PMID- 8499999 TI - A cautionary tale of the modified "pluck" nephroureterectomy. PMID- 8500000 TI - Percutaneous management of emphysematous pyelonephritis. PMID- 8500001 TI - Adult prostatic rhabdomyosarcoma. PMID- 8500002 TI - Transitional cell carcinoma in a Camey enterocystoplasty. PMID- 8500003 TI - The Mathieu operation. Is a urethral stent mandatory? PMID- 8500004 TI - Preliminary vascular control before renal exploration for trauma. PMID- 8500005 TI - Suprapubic catheter--an unusual cause of acute retention. PMID- 8500006 TI - Re: Personal computers and urological research. P.G. Carter et al. Br. J. Urol., 69, 456-459, 1992. PMID- 8500007 TI - Molecular analysis of the plasmid-borne bed gene cluster from Pseudomonas putida ML2 and cloning of the cis-benzene dihydrodiol dehydrogenase gene. AB - Pseudomonas putida ML2 contains a large catabolic plasmid, pHMT112, carrying genes that encode the dioxygenase and dehydrogenase involved in the catabolism of benzene via the ortho or beta-ketoadipate pathway. pHMT112 was derived from a larger and less stable plasmid in P. putida ML2 following growth on succinate as carbon and energy source but was, however, stably maintained in P. putida even in the absence of selection for growth on benzene. Cleavage sites for the restriction endonucleases DraI, XbaI, and BamHI were mapped on the plasmid. A region of the plasmid, downstream of the benzene dioxygenase genes (bedC1C2BA), was found to encode the cis-benzene dihydrodiol dehydrogenase gene (bedD). Recombinant Escherichia coli containing bedC1C2BAD genes was found to express benzene dioxygenase and dehydrogenase activity, indicated by the production of catechol when incubated in the presence of benzene. Hybridization using benzene dioxygenase genes as probes was used to construct a restriction map of the 35.5 kb XhoI-DraI fragment on which the bed operon was located. PMID- 8500008 TI - Cereal grain digestion by selected strains of ruminal fungi. AB - The ruminal fungi Orpinomyces joyonii strain 19-2, Neocallimastix patriciarum strain 27, and Piromyces communis strain 22 were examined for their ability to digest cereal starch. All strains digested corn starch more readily than barley or wheat starch. Orpinomyces joyonii 19-2 exhibited the greatest propensity to digest starch in wheat and barley, whereas the digestion of these starches by N. patriciarum 27 and P. communis 22 was limited. Media ammonia concentrations were lower when fungal growth was evident, suggesting that all strains assimilate ammonia. Fungi formed extensive rhizoidal systems on the endosperm of corn, but O. joyonii 19-2 was the only strain to form such systems on the endosperm of wheat and barley. All strains penetrated the protein matrix of corn but did not penetrate starch granules. Starch granules from all three cereals were pitted, evidence of extensive digestion by extracellular amylases produced by O. joyonii 19-2. Similar pitting was observed on the surface of corn starch granules digested by N. patriciarum 27 and P. communis 22, but not on wheat and barley starch granules. The ability of ruminal fungi to digest cereal grains depends on both the strain of fungus and the type of grain. The extent to which fungi digest cereal grain in the rumen remains to be determined. PMID- 8500009 TI - Accumulation of intracellular carbon reserves in relation to chloramphenicol biosynthesis by Streptomyces venezuelae. AB - Two chloramphenicol-producing strains of Streptomyces venezuelae accumulated small amounts of polyhydroxybutyrate during exponential growth; the compound disappeared from the mycelium as the cultures entered stationary phase. Depletion of polyhydroxybutyrate coincided with chloramphenicol production but the amount of polymer stored in the mycelium was insufficient to supply the precursor requirement for biosynthesis of the antibiotic. Accumulation of polyhydroxybutyrate in the S. venezuelae strains was appreciably lower than in two other streptomycetes examined. Glycogen and lipids accumulated in the mycelium of S. venezuelae 13s during the stationary phase, after nitrogen depletion; under the culture conditions used, they were the principal storage compounds in S. venezuelae. Trehalose was absent from the mycelium in vegetative cultures grown under nonsporulating conditions but it was abundant in spores obtained from submerged and surface cultures. Glycogen and polyhydroxybutyrate were absent from spores. PMID- 8500010 TI - Pulsed-field gel electrophoresis applied for comparing Listeria monocytogenes strains involved in outbreaks. AB - Recent food-borne outbreaks of human listeriosis as well as numerous sporadic cases have been mainly caused by Listeria monocytogenes serovar 4b strains. Thus, it was of interest to find out whether a certain clone or a certain few clones were responsible for these cases and especially for outbreaks. We used pulsed field gel electrophoresis of large chromosomal DNA restriction fragments generated by ApaI, SmaI, or NotI to analyse 75 L. monocytogenes strains isolated during six major and eight smaller recent listeriosis outbreaks. These strains could be divided into 20 different genomic varieties. Thirteen of 14 strains isolated during major epidemics in Switzerland (1983-1987), the United States (California, 1985) and Denmark (1985-1987) demonstrated indistinguishable DNA restriction patterns. In contrast, strains responsible for the outbreaks in Canada (Nova Scotia, 1981), the United States (Massachusetts, 1983), France (Anjou, 1975-1976), New Zealand (1969), and Austria (1986) and some smaller outbreaks in France (1987, 1988, 1989) were each characterized by particular combinations of DNA restriction patterns. Seventy-seven percent of the tested strains could be classified into the previously described ApaI group A (Brosch et al. 1991), demonstrating a very close genomic relatedness. Because 49% of the epidemic strains selected for this study belonged to phagovar 2389/2425/3274/2671/47/108/340 or 2389/47/108/340, fifty-six additional strains of these phagovars, isolated from various origins, were also typed to determine whether differences in DNA restriction profiles between epidemic and randomly selected strains of the same phagovars could be pointed out. Variations in DNA patterns appeared more frequently within randomly selected strains than within epidemic strains. PMID- 8500011 TI - Superoxide dismutase activity in root-colonizing pseudomonads. AB - Several saprophytic fluorescent pseudomonads that are aggressive root colonizers express similar specific activities of superoxide dismutase during growth in liquid culture. The pseudomonads have the potential to produce hydrogen peroxide sensitive and hydrogen peroxide insensitive isoforms of superoxide dismutase with distinct mobilities in nondenaturing polyacrylamide gel electrophoresis. Synthesis of the hydrogen peroxide insensitive form is enhanced by limited iron availability, by exposure to Mn2+, and to a lesser extent by external sources of superoxide anion. Unlike Pseudomonas aeruginosa, a root-colonizing strain of Pseudomonas putida did not show regulation of isoform pattern by phosphate availability. A plasmid potentially encoding the pseudomonad hydrogen peroxide sensitive form complemented the superoxide dismutase deficiency in a mutant of Escherichia coli lacking expression of both Fe and Mn genes. Contact between the plant root and pseudomonad or E. coli cells that lack or express superoxide dismutase did not influence superoxide anion production from root surface enzymes. The pseudomonad and the superoxide dismutase deficient and producing E. coli strains survived exposure to the root equally well. Only the hydrogen peroxide sensitive isoform of superoxide dismutase was detected in P. putida cells associated with bean root surfaces. PMID- 8500012 TI - Nitroaromatic compounds serve as nitrogen source for Desulfovibrio sp. (B strain). AB - A sulfate-reducing bacterium, Desulfovibrio sp. (B strain), isolated from a continuous anaerobic digester, used various nitroaromatic compounds such as 2,4 dinitrophenol, 2,4-dinitrotoluene, and 2,6-dinitrotoluene as sole nitrogen sources for growth and also used these compounds as electron acceptors in the absence of sulfate in the culture medium. More than 60% of the nitroaromatics were transformed within 6 days of incubation. The organism also used aniline as sole nitrogen source, but not as an electron acceptor. Desulfovibrio sp. (B strain) did not use nitroaromatics as sole source of carbon and energy. The nitro groups in the aromatic ring were reduced and reductively deaminated to ammonia, which was used as nitrogen source, leaving the aromatic ring intact. Even though this organism did not degrade the nitroaromatics completely, it may be useful in degrading nitroaromatics in contaminated soil and water containing other aromatic degraders in a syntrophic culture system under anaerobic conditions. PMID- 8500013 TI - Kasugamycin inhibition of nonsense suppression by thymine-requiring strains of Escherichia coli K12. AB - Thymine-requiring strains of Escherichia coli suppress nonsense and frame-shift mutations. This appears to occur during translation, suggesting that the lack of activity of an enzyme thymidylate synthase, required for the synthesis of a DNA precursor, alters the fidelity of translation. The aminoglycoside antibiotic kasugamycin, which enhances translational accuracy in vitro, prevents thymine requiring cells from suppressing. The inhibition of suppression by kasugamycin is not prevented by the introduction of two different kasugamycin-resistance mutations, although the dose required for inhibition increases. These observations support the conclusion that suppression occurs during translation. PMID- 8500014 TI - Postgraduate training: new and improved or "a real mess"? PMID- 8500015 TI - Where is the evidence? PMID- 8500016 TI - Issue of sexual exploitation of patients by physicians. PMID- 8500017 TI - Nazi medicine. PMID- 8500018 TI - Nazi medicine. PMID- 8500019 TI - Nazi medicine. PMID- 8500020 TI - Radiography of the ankle. PMID- 8500021 TI - Radiography of the ankle. PMID- 8500022 TI - Savings at what cost? PMID- 8500023 TI - Hemophilia and HIV infection. PMID- 8500024 TI - Epidural analgesia during labour. PMID- 8500025 TI - Active euthanasia: should polls be action guides? PMID- 8500026 TI - Canadian physicians and euthanasia: 4. Lessons from experience. PMID- 8500027 TI - Compensating occupational diseases: a medical and legal dilemma. PMID- 8500028 TI - Group A Streptococcus: a re-emergent pathogen. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. AB - Rheumatic fever is still rare in North America but must continue to be considered in the appropriate clinical setting. Invasive or severe GABHS disease remains unusual and is unlikely to be missed by the practitioner; however, it is essential that GABHS infection be considered as a possible cause of a severe sepsis-like syndrome. Currently the routine management of GABHS infection is unchanged; however, heightened awareness of the infection's rare, more serious complications is needed. PMID- 8500029 TI - Alberta euthanasia survey: 1. Physicians' opinions about the morality and legalization of active euthanasia. AB - OBJECTIVE: To ascertain the opinions of a sample of Alberta physicians about the morality and legalization of active euthanasia, the determinants of these opinions and the frequency and sources of requests for assistance in active euthanasia. DESIGN: Cross-sectional survey of a random sample of Alberta physicians, grouped by site and type of practice. SETTING: Alberta. PARTICIPANTS: A total of 2002 (46%) of the licensed physicians in Alberta were mailed a 38-item questionnaire in May through July 1991; usable responses were returned by 1391 (69%). RESULTS: Of the respondents 44% did believe that it is sometimes right to practice active euthanasia; 46% did not. Moral acceptance of active euthanasia correlated with type of practice and religious affiliation and activity. In all, 28% of the physicians stated that they would practice active euthanasia if it were legalized, and 51% indicated that they would not. These opinions were significantly related to sex, religious affiliation and activity, and country of graduation. Just over half (51%) of the respondents stated that the law should be changed to permit patients to request active euthanasia. Requests (usually from patients) were reportedly received by 19% of the physicians, 78% of whom received fewer than five. CONCLUSIONS: This survey revealed severely disparate opinions among Alberta physicians about the morality of active euthanasia. In particular, religious affiliation and activity were associated with the polarized opinions. The desire for active euthanasia, as inferred from requests by patients, was not frequent. Overall, there was no strong support expressed by the physicians for the personal practice of legalized active euthanasia. These data will be vital to those involved in health education and public policy formation about active euthanasia in Alberta and the rest of Canada. PMID- 8500030 TI - Alberta euthanasia survey: 2. Physicians' opinions about the acceptance of active euthanasia as a medical act and the reporting of such practice. AB - OBJECTIVE: To ascertain the opinions of Alberta physicians about the acceptance of active euthanasia as a medical act (the "medicalization" of active euthanasia) and the reporting of colleagues practising active euthanasia, as well as the sociodemographic correlates. DESIGN: Cross-sectional survey of a random sample of Alberta physicians, grouped by site and type of practice. SETTING: Alberta. PARTICIPANTS: A total of 2002 (46%) of the licensed physicians in Alberta were mailed a 38-item questionnaire in May through July 1991; usable responses were returned by 1391 (69%). RESULTS: Although only 44% of the respondents considered active euthanasia morally "right" at least 70% opted to medicalize the practice if it were legal by restricting it to be performed by physicians and to be taught at medical sites. Even though active euthanasia is criminal homicide in Canada, 33% of the physicians stated that they would not report a colleague participating in the act of anyone, and 40% and 60% stated that they would not report a colleague to medical or legal authorities respectively. Acceptance or rejection of active euthanasia as a medical act was strongly related to religious affiliation and activity (p < 0.01). CONCLUSIONS: This survey about active euthanasia revealed profound incongruities in the opinions of the sample of Alberta physicians concerning their ethical and social duties in the practice of medicine. These data highlight the need for relevant modifications of health education policies concerning biomedical ethics and physicians' obligations to society. PMID- 8500031 TI - Medical direction and control of emergency medical services in Canada. AB - OBJECTIVE: To determine the level of physician involvement in prehospital emergency medical services (EMS) in Canada, as compared with published principles of medical control and direction. DESIGN: Mail and telephone survey by means of a questionnaire from March to November 1991. SETTING: All Canadian provinces and territories. PARTICIPANTS: Fifty-six key prehospital EMS physicians, senior government administrators and senior representatives of the agencies responsible for licensing physicians in each province or territory. MAIN OUTCOME MEASURES: Responses to questions regarding the legislation, organization, administration, practice and regulation of medical direction and control by physicians in each province or territory. RESULTS: EMS legislation describing medical direction and control was completely lacking in five provinces and both territories and was incomplete in the remainder. Provincial guidelines written by physicians for prehospital patient care were present in only four provinces. Formal organization of medical directors varied from none to partially remunerated networks. Regional medical-director systems were present in three provinces, and local medical directors were required for all communities in three. Most rural ambulance services were found to engage physicians only when there was local interest. CONCLUSIONS: The level of physician involvement in the medical direction and control of EMS appears to be inconsistent across Canada and insufficient in most jurisdictions, as compared with accepted principles. PMID- 8500032 TI - Guidelines for the investigation of individuals who were place under surveillance for tuberculosis post-landing in Canada. Canadian Thoracic Society, the Tuberculosis Directors of Canada and the Department of National Health and Welfare. AB - There are 2 parts to this article. Part 1 is a preamble, jointly prepared by Immigration and Overseas Health Services, Medical Services Branch and the Bureau of Communicable Disease Epidemiology, LCDC, Department of National Health and Welfare, to provide background information regarding the medical assessment of immigrants prior to landing in Canada. Part 2 is a set of guidelines for the investigation of individuals who were placed under surveillance for tuberculosis post-landing in Canada. It was jointly prepared by the Canadian Thoracic Society, the Tuberculosis Directors of Canada and the Department of National Health and Welfare in consultation with the provincial and territorial epidemiologists and has been approved by the Canadian Lung Association and the Canadian Thoracic Society. PMID- 8500033 TI - Guidelines for the identification, investigation and treatment of individuals with concomitant tuberculosis and HIV infection. Bureau of Communicable Disease Epidemiology, Canada Department of National Health and Welfare. AB - The following recommended guidelines, jointly prepared by the Canadian Thoracic Society, the Tuberculosis Directors of Canada, and the Department of National Health and Welfare in consultation with the provincial and territorial epidemiologists, AIDS coordinators and HIV caregivers, and approved by the Canadian Lung Association and the Canadian Thoracic Society are provided to assist health care workers who are caring for patients in the overlapping group. PMID- 8500034 TI - Duchenne muscular dystrophy, cystic fibrosis, myotonic dystrophy: gene to protein. PMID- 8500035 TI - An address on what shall I do about it? 1929. PMID- 8500036 TI - The death of a doctor. PMID- 8500037 TI - CMA launches major campaign to support new MDs' right to practise. PMID- 8500038 TI - Fiscal problems forcing provinces to take closer look at health care fraud. PMID- 8500039 TI - Marathon man. PMID- 8500040 TI - Organization helps travellers cope with medical problems while abroad. PMID- 8500041 TI - Threat of skin cancer changing the way Australians live. PMID- 8500042 TI - Native health care: "unless you look at the broader picture, you can get lost". PMID- 8500043 TI - Hospitals' use of computer-based information systems raises legal issues. PMID- 8500044 TI - Spanish flu outdid WWI in number of lives claimed. PMID- 8500045 TI - Love of honour, dread of shame: medical services on the Plains of Abraham. PMID- 8500046 TI - History has given Quebec medicine a special flavour. PMID- 8500047 TI - Frances Redmond: a pioneer in community health in Vancouver. PMID- 8500048 TI - Canadian National Breast Screening Study: public health implications. PMID- 8500049 TI - The NBSS and public health policy. PMID- 8500050 TI - Canadian National Breast Screening Study. Public health implications: a clinician's perspective. PMID- 8500051 TI - What's in a gender? PMID- 8500052 TI - An evaluation of breastfeeding promotion literature: does it really promote breastfeeding? AB - Breastfeeding pamphlets are being produced for new mothers by both commercial and nonprofit sources in increasing quantities. A regional lactation committee decided to evaluate these materials on the basis of accuracy, degree of positive approach to breastfeeding, readability and compliance with the WHO/UNICEF Code on the Marketing of Breast Milk Substitutes. Results indicate that materials produced by non-profit sources scored higher in positive approach accuracy and WHO Code compliance compared with commercial sources. Only 2 of 22 pamphlets in the sample were written within the recommended reading level of Grade 5-8. None of the materials met all of the criteria for good promotional breastfeeding literature. PMID- 8500053 TI - [Characteristics of 2829 women who obtained an abortion at the Family Planning Clinic at the Laval University Hospital Center]. AB - Induced abortion rates have remained stable in Canada for the last ten years, while, in Quebec, they have been on the rise since 1970. This descriptive study was performed in a family planning clinic in Quebec City where induced abortion is available on demand until 16 weeks of gestational age and was obtained by 2,829 women over a period of 20 months during 1988-90. These women were mostly young unmarried and well educated; being at school or in the workforce, they used abortion to postpone childbearing. This study underlines the need for a better understanding of the determinants of both induced abortion and contraceptive use and of the psychosocial aspects of induced abortion. PMID- 8500054 TI - Sharps utilization and disposal in British Columbia physicians' offices. AB - To determine the pattern of sharps utilization and disposal in British Columbia physicians' offices, a questionnaire was mailed to all office-based physicians belonging to the British Columbia Medical Association (BCMA). 1,167 physicians (25%) responded. Over 166,000 sharps per month were used by responding physicians, a per physician use of 95 per month. 67% of physicians used a specific plastic container for sharps disposal and 22% used a recycled container. 40% of the used containers were returned to a hospital or laboratory for disposal; 29% contracted out to a waste removal company, 18% placed with regular office garbage and 4% taken directly to a landfill or incinerator. Most offices (64%) had access to an autoclave or chemclave but few physicians (2%) sterilized their sharps waste prior to disposal. The recommended options for discarding used sharps containers in the office setting are: return to a hospital or laboratory for processing with their infectious waste; removal by a waste disposal service; or sterilization followed by disposal with regular garbage. PMID- 8500055 TI - Job satisfaction of Canadian public health nutritionists. AB - This study investigated the job satisfaction of public health nutritionists employed in provincial and municipal/regional departments of health in Canada. 153 (78%) of all eligible Canadian public health nutritionists responded to a mailed questionnaire. 89% of respondents indicated that overall, they were very satisfied or satisfied with their jobs. Although only 5% were dissatisfied or very dissatisfied, 31% would have doubts about recommending the profession to young people today, and 30% would choose a different profession if they could start again. Nutritionists who would recommend the profession had significantly higher (p < .05) levels of overall job satisfaction. Analysis of 23 job dimensions showed that nutritionists were most satisfied with their professional independence and stimulation. They were least satisfied with financial rewards and opportunities for advancement. The study provides direction on actions that may be taken to increase job satisfaction among Canadian public health nutritionists. PMID- 8500056 TI - Mortality among employees at a hydrometallurgical nickel refinery and fertilizer complex in Fort Saskatchewan, Alberta (1954-1984). AB - We examined the mortality experience of 1,643 male hydrometallurgical nickel refinery and fertilizer employees who were employed at Sherritt Gordon Limited in Fort Saskatchewan, Alberta for at least 12 continuous months during the years 1954 to 1978. Mortality ascertainment was obtained utilizing the Canadian Mortality Data Base maintained by Statistics Canada and covered the years 1954 through 1984. Cause-specific mortality analyses were accomplished using male, age and calendar-year adjusted death rates for Canada and the province of Alberta. Total mortality was observed to have been significantly below expectation. Statistically significant fewer observed deaths were found for circulatory disease, ischemic heart disease and deaths due to accidents, poisonings and violence while the category "other forms of heart disease" demonstrated a statistically significant elevation of observed deaths. No association was found in this study between employment at the Sherritt Gordon hydrometallurgical nickel refinery and the subsequent development of respiratory cancer. PMID- 8500057 TI - Monitoring of drug utilization in public health surveillance activities: a conceptual framework. AB - The surveillance of individual and aggregate patterns of prescribed medication can potentially provide some very useful information to those involved in public health. At present however, this activity has attracted relatively little attention in Canada. This article will introduce a conceptual framework with which to examine the possibilities of prescription drug monitoring as a tool for public health surveillance. The sources of data available to undertake this activity as well as their limitations, will be presented along with some recent concrete applications. PMID- 8500058 TI - Physiological profile of fire fighters compared to norms for the Canadian population. AB - The purpose of this study was to determine the physical fitness level of Canadian fire fighters and to compare them to norms for Canadians of similar age and sex. The subjects were 1,303 male fire fighters from the Montreal fire department between the ages of 19 and 58 years. The subjects were categorized into four age groups: 19-29 years (n = 351), 30-39 years (n = 408), 40-49 years (n = 408), and 50-59 years (n = 136). Physical fitness was evaluated using the Canadian Standardized Test of Fitness. The test battery included: 1) pre-test screening, 2) anthropometric assessment, 3) cardiovascular, 4) flexibility and 5) muscular endurance measurements. Compared to the norms for the Canadian population of similar age, the fire fighters have: 1) higher body mass, body mass index and waist-to-hip ratio, 2) higher flexibility, 3) higher muscular endurance and 4) lower cardiovascular endurance. The lower cardiovascular endurance of the fire fighters was attributed to elevated body mass and an elevated heart rate response to the step test. It is unknown whether the heart rate response reflects long term effects of exposure to carbon monoxide and vapours from combustible materials and chemicals. PMID- 8500059 TI - Factors associated with self-reported use and non-use of assistive devices among impaired elderly residing in the community. AB - We report an analysis of data from the Health and Activity Limitation Survey (HALS) pertaining to the use of assistive devices. The focus is on elderly people reporting an impairment who did not use assistive devices. The degree of impairment, type of impairment, and socio-demographic variables were analyzed for their association with non-use of assistive devices. The non-use of assistive devices was often found to be consistently and strongly correlated for women who report social isolation, less education and who reside in rural areas, suggesting that these groups could be the target for policy initiatives. PMID- 8500060 TI - Motor vehicle traffic accidents in Canada, 1978-87 by time of occurrence. PMID- 8500061 TI - Evaluation of an influenza vaccination program for nursing home staff. PMID- 8500062 TI - Health and productivity savings from increased alcoholism treatment in Ontario. PMID- 8500063 TI - Trend highlights from the Ontario Student Drug Use Survey, 1977-1991. PMID- 8500064 TI - To BSE or not to BSE? That is the question. PMID- 8500065 TI - Breast cancer. PMID- 8500066 TI - [Effect of personality disorders on response to cognitive behavioral therapy of panic disorder with agoraphobia]. AB - This study measures the effect of personality disorders on the efficacy of treatment of agoraphobia. Forty-one patients suffering from panic disorder with agoraphobia are evaluated for the presence of a personality disorder (according to DSM-III-R criteria) before the onset of treatment. The treatment consists in 14 sessions of behavioural cognitive therapy. Various measures of agoraphobic avoidance are obtained before (pre-test) and after the end of treatment (post test, three month follow-up). Effect of treatment reaches statistical and clinical significance for all patients. Grouping of patients according to presence or absence of personality disorder shows no significant difference between the groups before or after treatment on scores of agoraphobia. A subgroup of patients with dependent personality disorder does not differ on measures of agoraphobic avoidance from patients without personality disorders or with other personality disorders. The discussion points out methodological limitations, differences in our study from other studies regarding the effect of personality on the treatment outcome of panic disorder with agoraphobia, as well as possibilities for future studies. PMID- 8500067 TI - [Consultation-liaison psychiatry: a prospective study in a general hospital milieu]. AB - This study was conducted in Halifax, Nova Scotia, in a 740 bed university general hospital. For a period of two years, a prospective collection of data on 692 psychiatric consultations showed that 60% of all consultations came from internal medicine departments. Medical and psychiatric comorbidity was found in 50% of the patients; depression was diagnosed in 27.5% of the cases but schizophrenia in only 1.7%. Suicidal ideation was reported by 24% of the patients, 11.6% of them wishing to die imminently. More than 50% of suicidal patients were under 35 years of age; 42% of them were dependent on alcohol. Almost 30% of the patients seen in consultation admitted to being addicted to alcohol, 22% to benzodiazepines and 14% to illicit drugs. Among the ex-alcoholic patients, a significant dependence in benzodiazepine use was found. The patients with addictions to street drug had a greater suicide risk and were at the same time abusing alcohol. This paper will describe the overall functioning of a consultation-liaison psychiatric service and will analyze the impact of psycho-active substance abuse in a general hospital setting. The results will be compared with those in the literature. PMID- 8500068 TI - Patients' characteristics and consumer satisfaction on an inpatient child psychiatric unit. AB - This paper reports the results of a chart review and consumer satisfaction evaluation of referrals to a tertiary care child psychiatric inpatient unit. The evaluation involved an examination of the types of child and family difficulties treated during the period of the study; the nature and extent of assessment, treatment and follow-up; treatment outcome and parental perception of factors related to treatment outcome; and the satisfaction of both the parents and referral sources. Results indicated that children admitted for treatment were a heterogeneous group with severe difficulties from families with a number of problems. Most parents and referring therapists were very satisfied with the treatment, recommendations and follow-up provided. Significant correlations were observed between the parents' and referring therapist's satisfaction with the service and the extent to which home based problems were addressed during the child's stay in hospital. In addition, some suggestions are given for strategies to improve services. The findings are discussed with special reference to the value of program evaluations for inpatient child psychiatric services. PMID- 8500069 TI - The symptom structure of panic attacks in depressed and anxious patients. AB - This study examined the panic symptom profiles of three diagnostic groups: those with panic disorder and no history of major depression; those with panic disorder with a history of major depressive episode but no current depression; and those current major depression with panic disorder. Patients were compared on the frequency of specific panic attack symptoms based on structured interview responses. The symptom profiles of all three groups were significantly correlated. The patients with past and current depressive episodes had the most similar symptom structure. PMID- 8500070 TI - Deinstitutionalization: the Italian experience. PMID- 8500071 TI - Comprehensive community care without long stay beds in mental hospitals: trends from an Italian good practice area. AB - Despite the scientific evidence that long stays in mental hospitals are clinically deleterious, inhumane and probably not cost-effective, this practice still occurs in most Western countries. The continued use of long stay beds in mental hospitals is a policy decided by many authorities, including psychiatrists. Alternatives to the mental hospital exist and may limit the use of hospital beds through comprehensive community care that also includes proper residential provisions. Alternatives may also decrease, but not impede the tendency to chronicity in some patients, who become long term users of these community services. Italy passed a law in 1978 prohibiting admissions to mental hospitals and encouraging the development of community care. In South Verona, Italy, the policy has been properly implemented and evaluated. Data from the case register and intensive studies of a cohort of patients will be used to show that long stay hospitalization can be discontinued while meeting the needs of the most severely handicapped patients. Implications of South Verona's experience for future training of psychiatrists will also be discussed. PMID- 8500072 TI - Recent trends in mental health services in Italy: an analysis of national and local data. AB - This paper reviews trends in Italian mental health services after the implementation of the 1978 Mental Health Act. Data available at the national level on public and private inpatient services, community mental health centres, residential and day care facilities are presented and discussed. Findings from two case-register areas, where comprehensive community services according to the Mental Health Act have been implemented, are discussed. Public mental hospitals are no longer used for psychiatric treatment, except for a small number of long stay patients. General hospital psychiatric units are the only setting in the public sector where psychiatric patients can be admitted. In private mental hospitals, the number of residents has decreased, while admissions have remained stable. However, community services are unevenly distributed and residential facilities are generally lacking. Little is known about quality of care provided, although data from some pilot studies are encouraging. Stable admission rates to forensic mental hospitals suggest that the criminalization of mentally ill has not increased. The effect of changing patterns of mental health care on suicide rates are discussed. PMID- 8500073 TI - [Utilization of expert systems in psychiatry]. AB - Are expert systems liable to be used as consultants in psychiatry? Most expert systems deal with an over-restricted part of psychiatry and cannot be a real help in everyday care. Moreover, most of them are not actually validated (the comparison between the system's and the expert's conclusions in a few cases is not enough). Another problem is that they reflect the uncertainties of nosographic problems. Validation of such systems needs the careful checking of the logical structure of the underlying nosography, the fitness of the structure's knowledge base and the fitness of the inference engine. Moreover, the naive use of the system by untrained clinicians is the best means of validation since it provides real life proof of the ability of expert systems to make diagnoses in unselected cases where the need for a common diagnostic reference is clear (for example, epidemiologic, psychopharmacological ornosographic research). Some of the best known expert systems in the field of psychiatry are reviewed and another expert system, Adinfer, is presented. Developed since 1982, Adinfer is a forward-tracking level O system (in its simplified version for micro-computers). The knowledge base is a translation of the DSM-III-R into production rules. The program has been included in several software packages and used in many clinical studies, both among psychiatrists and physicians. The program has been validated with 1,141 unselected cases, and with 47 physicians: an 83% agreement rate was found between the system's and the physician's diagnoses, taking into account that the clinicians were asked to give their conclusions according to their usual nosography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500074 TI - Mood disorders: developmental and precipitating events. AB - A consecutive sample of 298 mainly non psychotic outpatients was classified according to DSM-III criteria. The differences in the reports from childhood and the precipitating events among the various subgroups of mood disorders (bipolar disorder, major depression, cyclothymic disorder, dysthymic disorder) and a residual group of patients with other mental disorders were examined. The patients in the non bipolar group reported more traumatic childhood experiences than the patients in the bipolar group. Precipitating events among patients in the group with major depression consisted more often of acute external stressors. Developmental factors and precipitating events in adulthood seem to be relevant in differentiating between the depressive disorders. The study supports the validity of the unipolar-bipolar distinction. The cyclothymic group seem to be a special variant of the major mood disorders. PMID- 8500075 TI - [Child development: primary influences, primary stages and foundations of psychotherapy]. AB - Recent research on child development and on infant-mother psychotherapy is reviewed. The problem of continuity or discontinuity of early patterns is thus brought out, as well as the possibility of change under the influence of environmental modifications or in psychotherapy. After briefly presenting the most often proposed mechanisms to explain change, the possibility is suggested that such change could be better conceptualized by using fundamental modes of development that can be particularly observed in mother-infant or parent-young child interaction. PMID- 8500076 TI - Schizoaffective disorders and negative symptoms. PMID- 8500077 TI - Hysteria--100 years after Charcot. PMID- 8500078 TI - Overdiagnosis of ADD. PMID- 8500079 TI - Pharmacological issues in the treatment of bipolar disorder: focus on mood stabilizing compounds. AB - The acute and chronic pharmacotherapy of bipolar disorder requires an understanding of the pharmacology of very dissimilar compounds--the mood stabilizers (lithium, carbamazepine and valproate) and several classes of antidepressants. No definitive data are available on the primary mode of action of mood stabilizers, and those used show no single pharmacological property. On the other hand, the pharmacokinetics and dynamics of these compounds are well studied. PMID- 8500080 TI - Rapid cycling bipolar disorder and its treatment with valproate. AB - A large subgroup of lithium-resistant manic patients are rapid cyclers and as many as 82% of them exhibit poor responses to lithium. Thus, a substantial percentage of poor responses to lithium is accounted for on the basis of rapid cycling. Although controlled trials have demonstrated the efficacy of carbamazepine for the treatment of rapid cycling bipolar disorder, the response to carbamazepine frequently deteriorates. Furthermore, its ability to auto-induce and hetero-induce drug metabolism complicates its routine use. These findings suggest that substantial numbers of rapid cyclers do not respond to either carbamazepine or lithium and that additional mood stabilizers are needed. Our recent findings on 101 rapid cycling bipolar patients continue to support the impression that valproate has marked antimanic efficacy and poor to moderate antidepressant properties. Most patients with mixed states exhibited good antimixed state responses but then became depressed. Predictors of a good antimanic response included decreasing or stable episode frequencies and non psychotic mania. Predictors of a good antidepressant response were non psychotic mania worsening over the years of the illness and absence of borderline personality disorder comorbidity. These open prospective trials, as well as other positive reports of valproate's efficacy in bipolar rapid cycling, await replication with ongoing, controlled maintenance trials. PMID- 8500081 TI - Treatment guidelines for valproate in bipolar and schizoaffective disorders. AB - An increasing number of uncontrolled and controlled studies have shown that the anticonvulsant drug valproate is effective for the acute and prophylactic treatment of some patients with bipolar disorder, including those who respond inadequately to or cannot tolerate treatment with lithium or carbamazepine. Uncontrolled studies suggest that valproate may be effective in some patients with schizoaffective disorder. In this article, studies of the efficacy of valproate for the treatment of bipolar and schizoaffective disorder are briefly reviewed, and clinical guidelines for its use in these patients are presented. PMID- 8500082 TI - Putting ethics into education. AB - Health care professionals are increasingly aware of the moral dimensions of their practice, and nurses are no exception. Changes in technology, in society and in nursing itself are demanding that nurses have ethical knowledge and skills. No matter what their area of clinical practice, today's nurses are increasingly confronted with ethical problems and the need to make ethical decisions. PMID- 8500083 TI - User fees: fair cost containment or a tax on the sick? AB - The federal government's reduction in transfer payments for health and education, in combination with a severe recession, has put provincial and territorial health ministries, health professionals and hospital administrators under immense financial pressure. In response, user fees are being discussed as one way to maintain medicare. Yet, charging levies for health services presents numerous ethical problems. User fees would end the universality of and accessibility to health care for many Canadians. Hence, they would constitute an unfair tax on the sick and the poor. The hardest hit would be the elderly, children, women, aboriginal people, the disabled and the chronically ill. PMID- 8500084 TI - You are your ethics. AB - The true extent of nurses' moral agency is to be found in their everyday encounters with clients. Yet, in today's procedure-bound health care institutions they have little freedom to exercise this morality. PMID- 8500085 TI - The right to refuse psychotropic drugs. AB - The right to refuse medical treatment has been accepted by the courts, health care personnel and consumers throughout Canada and the United States. Yet for some situations, the right to refuse medical treatment remains a matter of serious public debate. One of the most complex of these circumstances occurs when an institutionalized person is to be treated with a psychotropic drug. PMID- 8500086 TI - Questions of life and death. AB - The continuous evolution of health care technology has brought with it a growing need to evaluate the quality of the lives it saves or prolongs. Do Not Resuscitate (DNR) orders, euthanasia and living wills all raise the issue of who decides about the quality of a person's life. Although nurses and other health care professionals have developed codes of ethics to deal with these difficult evaluations, ethics are not law. Ethics are derived from culture, religion and societal and individual concepts of morality. Law is the set of rules a society chooses to enact and enforce. Real difficulty arises when health care providers must face a situation where personal and professional codes of ethics clash with the law. PMID- 8500087 TI - Anencephalic tissue transplantation. AB - The moral issue of whether to use organs from anencephalic newborns continues to perplex philosophers, physicians, nurses and others. In Canada, the medical profession has taken a firm stance that using these organs is not an ethical practice. Does this stance have a firm footing? Countering it are a number of arguments for using these organs. In addition, parental autonomy is limited by the present practice of having doctors control the decision. PMID- 8500088 TI - Ethics, the law and clinical decisions. AB - Many nurse educators wonder how they can teach their students to make ethical decisions. The Newfoundland School of Nursing has found a unique way to address this nebulous ability: the Moot Court. The Moot Court (or mock trial) enables students to explore the legal and ethical issues that arise in an imaginary court case. PMID- 8500089 TI - [Feminist strategies in nursing science]. AB - This article is the first of a two-part series that will be completed in next month's issue. The article illustrates through examples how nursing has the potential for sexual bias. It also demonstrates how the feminist movement can contribute to improving nursing practice. This month, the views of Peggy Chinn are discussed, outlining myths that limit the development or hinder the progress of non-sexist education in nursing. Myths that have become traditional, scientific male-centred methodologies now solidly rooted in the health care community are identified. The author explains that once the myths are identified, they should be extracted and isolated from the context of nursing. This is the way feminist research can be useful. Next month the author will define the feminist approach and how it applies to specific aspects of women's health. PMID- 8500090 TI - [Ethics: a challenge for education]. AB - Because of new advances in biomedical science and bio-technology, nurses are confronted with dilemmas for which no easy solutions are available. For this reason, it is becoming increasingly crucial that nursing students develop moral judgement. Nursing students find it difficult to relate the principles of ethics (moral conduct, duty and judgment) to concrete nursing situations. Blondeau (1986) believes the case study to be one of the most effective teaching strategies that can be used to raise moral sensitivity. However, it is very difficult to use this strategy with young adult students. The authors believe that if students learn ethical principles prior to the case study they will become aware of ethical problems and will be better prepared to discuss in depth ethical implications. They designed a self-learning module and compared the results with an equivalent group of students. Post-test cognitive results showed a difference between the two groups. Students using the new case study module expressed great satisfaction with the format, utilization and attitudes of this module. The approach proved useful since students were able to learn at their own pace. The time previously used to teach ethical principles was then allotted to class discussions and the process of ethical decision-making. PMID- 8500092 TI - Refugee health practices. PMID- 8500091 TI - Carseat study. PMID- 8500093 TI - Widows and decision-making. PMID- 8500094 TI - Fluorescent in situ hybridization assessment of chromosome 7 copy number in uncultured lung and kidney cells. AB - Trisomy 7 is common in cells cultured from nonneoplastic lung and kidney tissues, but the frequency of trisomy 7 in uncultured lung and kidney has not been determined. In this study, we used fluorescent in situ hybridization (FISH) to assess chromosome 7 copy number in uncultured interphase nuclei from lung and kidney specimens. All specimens had low level mosaicism for trisomy 7(1.5-5.25%), but control experiments indicated a potential wide margin of error in quantifying these events. PMID- 8500095 TI - Recurrent appearance of 14q+ chromosome associated with lymphoid crisis of Ph positive chronic myelogenous leukemia. AB - The 14q+ chromosomal anomaly commonly found in cases of lymphoid neoplasm recurrently occurred during the lymphoid crisis of a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). At presentation lymphoblasts, with pre-B phenotype increased, and both the Ph and 14q+ were found in the same metaphases. After treatment with vincristine and prednisolone, the patient entered into the chronic phase, and only a Ph was detected in 100% of the cells examined. The 14q+ reappeared at the recurrence of the lymphoid crisis, and then disappeared in the second chronic phase. The BCR/ABL mRNA, which is specific for CML, was detected in the blastic cells by a method using reverse transcriptase and polymerase chain reaction. The rearrangement of the immunoglobulin heavy chain gene (JH gene) was also detected in the blastic cells. These results suggest that the 14q+ was closely associated with the lymphoid crisis of the CML patient. PMID- 8500097 TI - Isodicentric Philadelphia chromosome in accelerated phase of chronic myeloid leukemia. AB - We describe a case of chronic myeloid leukemia (CML) associated with the finding of an isodicentric Philadelphia chromosome [idic(Ph)] during the accelerated phase of the disease. Chromosome study was carried out on bone marrow aspirate cells, obtained and cultured 5 months after the clinical diagnosis. The presence of an isodicentric Philadelphia chromosome was found in 90% of the analyzed metaphases; among the remaining observed metaphases, 6% showed two idic(Ph) chromosomes, 2% a t(9;22), and 2% a normal karyotype. The patient died 7 months after the clinical diagnosis, and 2 months after our chromosome study. The observation of idic(Ph) during CML has seldom been reported and the few cases studied have been inconsistently correlated with the course of the disease. In the present case, the finding of an idic(Ph) and the short patient survival from the time of clinical diagnosis may suggest the observed chromosome aberration as a factor associated with a poor prognosis. PMID- 8500096 TI - Molecular analysis of transforming growth factor beta in giant cell tumor of bone. AB - Giant cell tumor of bone (GCT) is a primary bone neoplasm with unique cytogenetic findings including telomeric associations. Elevated expression of message RNA for transforming growth factor beta (TGF beta), but not transforming growth factor alpha (TGF alpha), has been reported in this tumor. Further investigation of GCT was undertaken to determine whether genetic loci for TGF beta in GCT patients with and without chromosome abnormalities are altered. Due to the reported TGF beta overexpression in GCT, qualitative and quantitative Southern blot analyses with TGF beta 1 and TGF beta 2 and an internal control probe (p3-21) were performed with tumor DNA and DNA from normal tissue on ten patients with GCT and control individuals. No obvious TGF beta 1 or TGF beta 2 gene alterations were detected. Normal copy numbers were calculated when comparing tumor and normal DNA from GCT patients as well as DNA from control individuals. Abnormal chromosome findings, including telomeric associations, marker chromosome, double minutes, chromosome fragments, ring chromosomes (possibly representing intra-chromosome telomeric associations), and polyploid cells were observed in seven of the ten patients with GCT. Chromosomes 11, 16, 19, 20, and 21 were most commonly observed in telomeric associations, with the terminus of the long arm of chromosome 19 being the most frequent. We conclude that there are no TGF beta 1 or TGF beta 2 gene alterations detected in GCT with the methodologies described, and that telomeric associations are a reproducible cytogenetic characteristic of this neoplasm. PMID- 8500098 TI - Chromosome 22 heterozygosity is retained in most hyperdiploid and pseudodiploid meningiomas. AB - Hyperdiploid or pseudodiploid modal chromosome numbers were found characterizing six human meningiomas, and all six tumors were disomic for chromosome 22. The scarce previous reports on the subject suggest that, in these cytogenetic subgroups of meningiomas, duplication of the retained chromosome 22 occurs after the loss of the other member of the pair, thus correlating well with the main characteristic of meningiomas, that is, losses of 22. To verify this question, molecular genetic analyses were performed on DNA pairs from blood and tumoral samples of all six cases, using polymorphic markers for chromosome 22. Restriction fragment length polymorphism studies failed to show any loss of heterozygosity for markers located on this chromosome in all six cases, suggesting that a different mechanism to that previously proposed might take place in the hyperdiploid or pseudodiploid meningiomas; perhaps a submicroscopic involvement (microdeletions or inactivating mutations) of the meningioma locus (both alleles) may result in an effect similar to that produced by monosomy 22 (which probably unmasks recessive mutations on the retained allele), enhancing the development of meningiomas. PMID- 8500099 TI - Cellular radiosensitivity of patients with different types of neurofibromatosis. AB - Skin fibroblast cell strains were developed from nine Saudi patients with different types of neurofibromatosis (NF) and nine healthy subjects (controls), and their radiosensitivity was compared following chronic exposure to gamma radiation at a dose rate of 0.0076 Gy/min (1 Gy = 100 rads). Cells from both normal appearing skin and cafe-au-lait spots of the different NF patients (7 out of 9) clearly showed increased radiosensitivity, with D10 (dose resulting in 10% survival) values of 2.0-4.4 Gy for the former and 3.0-4.8 Gy for the latter, compared to the normal controls (with D10 values of 6.1-10.6 Gy). These data provide further evidence of an association of enhanced cellular sensitivity to chronic irradiation with NF regardless of the classes they belong to. Hypersensitivity to specific carcinogens may, thus, be a factor responsible for the increased propensity to cancer in these patients. PMID- 8500100 TI - Deletion(2)(p23) abnormality in a case of secondary acute myeloid leukemia. AB - We report a case of acute myeloid leukemia (M5a of the FAB classification), secondary to the myelodysplastic syndrome, showing a deletion of the short arm of chromosome 2 at p23 in the bone marrow cells. In addition, a duplication of chromosome 13,dup(13)(q12q14) was found. PMID- 8500101 TI - Lack of mutations in the P53 gene exons 5 to 8 in ataxia-telangiectasia. AB - Alterations of the TP53 tumor suppressor gene are present in various human malignancies and in the dominantly inherited Li-Fraumeni syndrome. Recently, a cell cycle checkpoint pathway involving p53 and GADD45 has been identified as defective in ataxia-telangiectasia. Using single strand conformation polymorphism analysis of PCR products, we looked for TP53 mutations in DNA of patients with AT. We did not find any mutation in 6 patients, suggesting that TP53 mutations are not directly involved in the cancer susceptibility observed in AT. PMID- 8500102 TI - Loss of chromosome Y in prostatic cancer cells but not in stromal tissue. PMID- 8500103 TI - Chromosome 12 origin in rings and giant markers in well-differentiated liposarcoma. PMID- 8500104 TI - A combination of lipopolysaccharide and B-cell growth factor increases lymphocyte metaphase yields in B-cell chronic leukemia. PMID- 8500105 TI - Fifth International Workshop on Chromosomes in Solid Tumors. Overview. PMID- 8500106 TI - p53 and the Li-Fraumeni syndrome. AB - The Li-Fraumeni familial cancer syndrome was initially described in 1969 in a retrospective epidemiologic review of more than 600 pediatric sarcoma patients. The clinical definition of the syndrome has been refined in the last two decades by prospective analyses of several families. Despite these exhaustive studies, the gene or genes responsible for the unusual constellation of tumors in these families remained elusive until 1990, when it was demonstrated that germline abnormalities of the p53 tumor suppressor gene could account for the occurrence of cancer in many classic Li-Fraumeni families. Identification of the molecular events that yield this phenotype has led many researchers to pursue several lines of investigation to improve our understanding of the significance of such alterations. We discuss the clinical, epidemiologic, genetic, and biologic aspects of the association between p53 and the Li-Fraumeni family cancer syndrome. PMID- 8500107 TI - Cytogenetic survey of 32 cancers of the prostate. AB - Cytogenetic studies after short-term culture were performed on 32 adenocarcinomas of the prostate from patients without prior treatment. The tumor specimens, ranging from stage B1 to D1, were obtained by radical prostatectomy or diagnostic biopsies. Fourteen tumors showed a normal diploid chromosome complement in all metaphases examined. Clonal chromosomal alterations were detected in 16 tumor samples and the remaining two cases contained double minute (dmin) chromosomes in some cells. The most frequent numerical changes included loss the Y chromosome and trisomy 7, both found in four cases. The only recurrent structural aberration was del(10)(q24), seen in three cases both as a sole anomaly and within multiple rearrangements. Six patients showed cytogenetically unrelated clones. The occurrence of the chromosomal changes found in this study shows no relationship to certain histopathologic characteristics of the tumors. The recurrent finding of del(10)(q24) as sole anomaly and the evidence for clonal evolution in one patient demonstrates that this change is an early karyotypic event which may be important for the pathogenesis in at least a subset of prostatic cancers. PMID- 8500108 TI - Application of the direct beta counter Matrix 96 for cytotoxic assays: simultaneous processing and reading of 96 wells using a 51Cr-retention assay. AB - To assess the cytotoxic activity of immune cells, we have developed a 51Cr retention assay in which the radioactivity retained by 51Cr-labeled target cells, following coincubation with cytotoxic cells, is monitored using the automated Matrix 96 beta counter. The Matrix 96 is designed for simultaneously counting 96 samples isolated from a 96-well microplate. It uses 96 uniform and independent detectors operating on the principle of avalanche gas ionization in the Geiger Muller mode. Samples must be dry because the detectors are of the open-window type. Therefore, samples from the 96 wells of the microplate are simultaneously harvested onto a filter using the MicroMate 196, a 96-well cell harvester, dried and quantified in the Matrix 96. Usually the 51Cr isotope is measured by the detection of gamma radiation in gamma counters. The Matrix 96, however, monitors Auger electrons, which are also emitted by 51Cr. We have shown that the retention assay can be used to monitor the cytotoxic activity of activated lymphocytes including lymphokine-activated killer cells and tumor-infiltrating lymphocytes against various tumor cell lines. This assay is most suitable for experiments in which low E/T ratios are sufficient to detect highly cytotoxic cells, such as clone screening in cloning assays or in limiting-dilution analysis assays. These assays involve processing and reading large numbers of microplates. In this case, the retention assay monitored in the Matrix 96 will improve the work flow and decrease the amount of radioactive waste. PMID- 8500109 TI - Antitumor response independent of functional B or T lymphocytes induced by the local and sustained release of interleukin-2 by the tumor cells. AB - Transfection of tumor cells with a vector containing the entire coding sequence of human interleukin-2 (hIL-2) was previously shown to convert the tumorigenic murine fibrosarcoma line CMS-5 into a non-tumorigenic line. The failure of the IL 2-secreting tumor to grow in conventional (immunocompetent) mice was attributed to the activation of CD8+ T cells that exhibited tumor specificity and memory. In order to determine whether or not the IL-2 produced by the tumor may be activating tumor cytotoxic effector cells other than B or T cells we have repeated this study using immunodeficient SCID and SCID-beige mice as syngeneic tumor recipients. In contrast to the rapid growth of the wild-type tumor, the hIL 2-transfected cells (N2A/IL2/CMS5) did not grow, or grew more slowly and regressed, in the mice that lack functional B and T cells. The inhibition of tumor growth associated with the local release of IL-2 was reversed in mice treated with antiasialo-GM1 antibodies specific for natural killer (NK) lineage cells. In contrast to the studies with conventional mice, the IL-2-dependent effector cells in the immunodeficient mice exhibited no evidence of memory. In vitro analysis of spleen cells from tumor-bearing mice revealed the presence of effector cells able to lyse YAC-1 target cells as well as the wild-type CMS-5 and the IL-2-transfected variant tumor lines but unable to lyse P815 cells. The pattern of selective target cell killing and the kinetics of killing were indistinguishable from those observed using tumor necrosis factor alpha (TNF alpha) the mediator associated with natural cytotoxicity cell killing of tumor cells. Histopathology of the IL-2-secreting tumors in SCID mice reveals the presence of infiltrating lymphoid cells and macrophages that were not observed in the CMS-5 tumors. Consistent with the notion that the tumor killing in the SCID mice was mediated by TNF alpha, mice bearing IL-2-secreting tumors had elevated levels of serum TNF alpha and little or no effector cell activity, or TNF alpha was found in tumor-bearing mice treated with anti-asialo-GM1 antibody. The results indicate that the cytokine-induced tumor regression observed in the IL-2 transfected tumors is a more complex phenomenon than previously recognized and one that is mediated by effector cells of the NK cell and/or monocyte/macrophage lineages, in addition to CD8+ T cells. PMID- 8500110 TI - A mouse/human chimeric anti-(ganglioside GD3) antibody with enhanced antitumor activities. AB - Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin has been focused on as a target molecule for passive immunotherapy. We have cloned the cDNA encoding the immunoglobulin light and heavy chains of an anti-GD3 monoclonal antibody KM641 (murine IgG3, kappa), and constructed the chimeric genes by linking the cDNA fragments of the murine light and heavy variable regions to cDNA fragments of the human kappa and gamma 1 constant regions, respectively. The transfer of these cDNA constructs into SP2/0 mouse myeloma cells resulted in the production of the chimeric antibody, designated KM871, that retained specific binding activity to GD3. Indirect immunofluorescence revealed the same staining pattern for chimeric KM871 and the mouse counterpart KM641 on GD3-expressing melanoma cells. When human serum and human peripheral blood mononuclear cells were used as effectors in complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity respectively, the chimeric KM871 was more effective in killing GD3 expressing tumor cells than was the mouse counterpart KM641. Intravenous injection of chimeric KM871 markedly suppressed tumor growth in nude mice. The chimeric KM871, having enhanced antitumor activities and less immunogenicity than the mouse counterpart, would be a useful agent for passive immunotherapy of human cancer. PMID- 8500111 TI - IgM monoclonal antibody JD118 recognizes an inducible antigen target for human complement-mediated cytotoxicity against neoplastic B cells. AB - Cancer therapy using unconjugated monoclonal antibodies (mAb) has been limited by the lack of immune effector function of the mAb and antigenic modulation. JD118 is a cytotoxic murine IgM mAb with reactivity restricted to a subset of normal B cells, some monocytic series cells, and a large percentage of B cell hematopoietic neoplasms including acute and chronic leukemias and lymphomas. Specificity was determined on several hundred normal and neoplastic, hematopoietic and non-hematopoietic cells and tissues, as well as progenitor cells. JD118 was able to kill fresh human leukemias and lymphomas in the presence of human serum as a complement source with an LD50 of 100 ng/ml. At this mAb concentration, fewer than 4% of more than 10(5) available target sites were bound. Killing was not affected by changes in antigen expression observed during the cell cycle nor by loss of cell-surface targets via antigenic modulation. Cytotoxicity could be achieved with human serum diluted as low as 5%, suggesting that complement depletion in vivo should not limit activity. Autologous human serum could be used effectively as a complement source. The JD118 antigen target has not been identified, but it appears to be a glycoprotein. Up-regulation of antigen expression on normal B cells and chronic lymphocytic leukemia cells in vitro resulted in antigen-negative neoplasms becoming positive and thus targets for JD118 killing. The restricted expression, potent cytotoxic characteristics, and potential for up-regulation of its antigen make JD118 a possible candidate for ex vivo autologous bone marrow purging and in vivo therapeutic trials in patients with B cell neoplasms. PMID- 8500112 TI - The development and purification of a bispecific antibody for lymphokine activated killer cell targeting against the rat colon carcinoma CC531. AB - In vivo targeting of lymphokine-activated killer (LAK) cells to tumour deposits by bispecific monoclonal antibodies (bimAb) may be a way to improve adoptive immunotherapy. We developed a bimAb against adherent LAK (ALAK) cells and colon tumour CC531 in Wag rats. The bimAb was produced by somatic hybridization of two mouse hybridomas, one producing monoclonal antibodies (mAb) against CD8 (IgG2b, OX8), and the other producing mAb against a CC531-associated antigen (IgG1, CC52). A bimAb-producing clone was selected by an enzyme-linked immunosorbent assay with CC531 tumour cells. BimAb were purified from ascitic fluid by protein A affinity chromatography. Each of five pooled peak fractions was analysed by flow cytometry for the presence of bimAb. Most bimAb were found in a fraction that was eluted at pH 4.5 from protein A. FPLC analysis of this fraction revealed that no parental antibodies were present. The OX8 x CC52 bimAb greatly increased conjugate formation in vitro between ALAK cells and CC531. Results of 51Cr release assays with CC531 as target cells and ALAK cells as effector cells were not significantly different in the presence or in the absence of the bimAb. The methods we used here, a cell enzyme-linked immunosorbent assay and flow cytometry, are simple methods for development and purification of a bimAb when a functional selection method is not a priori available. The OX8 x CC52 bimAb we developed this way may increase in vivo tumour targeting of ALAK cells and thus augment antitumour effect in vivo. PMID- 8500113 TI - Factors, including transforming growth factor beta, released in the glioblastoma residual cavity, impair activity of adherent lymphokine-activated killer cells. AB - Adherent lymphokine-activated killer (A-LAK) cells were obtained from peripheral blood lymphocytes of patients with recurrent glioblastoma. In vitro features of A LAK cultures were assessed in comparison to those of non-adherent lymphokine activated killer (NA-LAK) cells of the same patients with regard to cytotoxic activity, proliferation and surface markers. Only in a minority of cases did A LAK cells show a markedly higher cytotoxicity on K562, Daudi and allogeneic glioblastoma cells. Nevertheless, A-LAK cells proliferated significantly better than NA-LAK and contained higher percentages of CD16+, CD56+ and CD25+ cells, indicating that A-LAK cells from these patients represent a subpopulation of lymphocytes enriched for activated natural killer cells. We also investigated whether immunosuppressive factor(s) were present in the tumour bed of recurrent gliomas. To this end, samples of glioblastoma cavity fluid (GCF), which accumulates in the cavity of subtotally removed tumour, were recovered and tested for the presence of immunosuppressive activity. All GCF samples analysed were shown to inhibit in vitro proliferation and antitumour cytotoxicity of 1-week cultured A-LAK cells in a dose-dependent manner. Such GCF activity was effectively antagonized by a transforming growth factor beta (TGF beta) neutralizing antibody, indicating the involvement of TGF beta in lymphocyte inhibition. These results show that in the tumour cavity remaining after subtotal glioblastoma resection a marked immunosuppressive activity, probably due to local release of TGF beta, is present; such activity may negatively influence the therapeutic effectiveness of local cellular immunotherapy. PMID- 8500114 TI - [Paroxysmal atrial fibrillation: the significance of the dynamic behavior of the atrial cycle]. AB - The aim of this study was to evaluate the dynamic atrial endocardial activation pattern during atrial fibrillation and to investigate the electrophysiologic changes related to the self-termination of the arrhythmia. Twenty patients with daily recurrences of lone paroxysmal atrial fibrillation episodes underwent electrophysiological study with contemporary recording of the atrial signal in high right atrium, low right atrium and coronary sinus. Sixty episodes lasting longer than 1 min were recorded, 22 spontaneous and 38 induced with a single extrastimulus. A significant correlation has been demonstrated for the mean of 100 consecutive intervals evaluated at the arrhythmia onset and the atrial functional refractory period (R = 0.73, p < 0.001). Mean FF length increased significantly in the minute preceding self-termination of atrial fibrillation in all the 3 recording sites. On the contrary, a significant decrease of mean FF length was documented in long lasting episodes. Self-termination of atrial fibrillation episodes implies a peculiar pattern of intra-atrial interval. Therefore the analysis of FF intervals seems to have pathophysiological implication and may be applied also to evaluate pharmacological interventions. PMID- 8500115 TI - [Transesophageal Doppler study of pulmonary venous flow: the role of atrial contraction]. AB - Pulmonary venous flow (PVF) pattern can be easily recorded by using transesophageal Doppler echocardiography. Recent reports suggest that the analysis of PVF pattern could be useful to better understand the role of atrial contraction on left ventricular filling. In order to evaluate the effect of loss of atrial contraction, we studied 50 consecutive patients with atrial fibrillation. We then compared the PVF pattern of atrial fibrillation with the normal pattern obtained from 20 healthy subjects. The reversal flow (A wave) resulting from atrial contraction was lost in patients with atrial fibrillation. The systolic flow was composed by 1 wave in almost all the patients and the peak velocity was reduced compared to normal sinus rhythm. On the contrary, the diastolic flow was increased comparing to normal subjects. In atrial fibrillation the flow shifted from systolic to diastolic filling. The restore of sinus rhythm induced a normalization of PVF pattern. PMID- 8500116 TI - [Primary mesothelioma of the pericardium: diagnostic methods. A case report]. AB - Clinical picture and diagnostic methods in a patient with primary pericardial mesothelioma are described. Echocardiography shows an intrapericardial mass in direct continuity with left ventricular wall. Magnetic resonance imaging is essential to define mass dimension and extension and show cardiac wall and contiguous tissues infiltration. The histological characteristics are defined by using TAC-guided needle biopsy and needle aspiration. PMID- 8500117 TI - [Percutaneous valvuloplasty in mitral stenosis]. AB - Since May 1991 to July 1992, 83 patients (mean age 49 +/- 13 years, 17 males and 66 females) underwent percutaneous mitral valvuloplasty according to Inoue's technique. Following Wilkins' criteria echo-score was < or = 8 in 46 patients and mono-commissural calcifications were present in 8 cases. Sixteen (19%) patients had previous surgical mitral commissurotomy and 15 (18%) had previous embolic events. The indications for the procedure were given on the basis of the echo score (ideal cases with score < or = 8). All patients but 2 were successfully treated. Two patients who developed mitral regurgitation grade 3+/4+ were referred to elective surgery. Mitral valve area increased from 1.1 +/- 0.2 to 2 +/- 0.3 cm2 (p < 0.001) and transvalvular pressure gradient fell from 16 +/- 5 to 6 +/- 3 mmHg (p < 0.001). Patients with previous surgical commissurotomy had a lower increase in mitral valve area than patients without previous surgery (p < 0.02). Patients with echo-score > 8 presented a more evident increase in mitral regurgitation than patients with good valvular anatomy, even if this difference was not significant. At 6 and 12 month follow-up respectively 2 and 1 restenosis occurred, but in 1 of these cases the residual valvular area was > 1.5 cm2. The authors conclude that in selected patients with mitral stenosis percutaneous mitral valvuloplasty seems to be an effective and safe treatment. Furthermore, immediate and middle-term results show that this technique can be performed without adjunctive risks and with satisfactory results also in cases of no ideal clinical and/or valvular conditions (echo-score > 8, previous surgical commissurotomy, history of embolism, mono-commissural calcifications). PMID- 8500118 TI - Efficacy of caries preventive strategies. Proceedings of the scientific conference of the European Academy of Paediatric Dentistry. Mary 5-6, 1992, Noordwijkerhout, the Netherlands. PMID- 8500119 TI - Systemic use of fluoride--other methods: salt, sugar, milk, etc. AB - An analysis of the literature evaluated the caries-protective effects of various methods of fluoridation. Salt fluoridation (250 or 350 mg F/kg) can be considered as equivalent to fluoridation of drinking water. Existing evidence suggests that milk fluoridation cannot be considered equivalent to fluoridation of either drinking water or salt because of problems of consistent delivery. Sugar, beverages (including tea), as well as fluoride-rich mineral waters are likely to be of only limited importance for caries prevention, but may be effective on an individual basis. PMID- 8500120 TI - Efficacy of preventive agents for dental caries. Systemic fluorides: water fluoridation. AB - The effectiveness of fluoridation has been documented by observational and interventional studies for over 50 years. Data are available from 113 studies in 23 countries. The modal reduction in DMFT values for primary teeth was 40-49% and 50-59% for permanent teeth. The pattern of caries now occurring in fluoride and low-fluoride areas in 15- to 16-year-old children illustrates the impact of water fluoridation on first and second molars. The secular changes in caries in Hartlepool, a natural fluoride area in the North East of England, shows only a modest change between 1949 and 1989. Information on the pre-eruptive effects of water fluoridation has been reviewed, suggesting that fluoridation should start at birth to provide optimal protection to primary teeth. At 15 years of age, the maximum DMFS reduction in a fluoridated area was due about half to the pre eruptive and about half to the post-eruptive effect of fluoride. PMID- 8500121 TI - Role of fluoride toothpastes in a caries-preventive strategy. AB - While the clinical relevance of fluoride toothpastes per se is firmly established, the multifactorial processes involved in causation and prevention of caries render it difficult to define their exact role in an overall caries preventive strategy. Therefore, an indirect pragmatic approach was chosen: the interpretation of secular trends in caries prevalence and other parameters is used to estimate the relative importance of this method of topical fluoride administration and to compare it with the contributions by other methods of prevention. All methods of caries prevention, with the exception of population administered measures such as fluoridation of drinking water or domestic salt, can only work when applied regularly and conscientiously. For this reason behavioural aspects such as compliance and the chances for widespread (if not universal) application have to be considered. There is indirect evidence that toothbrushing with fluoride toothpastes is a highly probable explanation for the decline of caries prevalence in developed countries since the 70s; moreover, toothbrushing, and the use of therapeutic dentifrices, is considered to meet spreading compliance because a 'healthy mouth' becomes more and more socially desirable in growing numbers of subpopulations. PMID- 8500122 TI - Evaluation of the use of topical fluoride gel. AB - Professionally applied topical fluoride should be used judiciously and is indicated only in patients with moderate or high caries activity. While the anti caries effectiveness of acidulated phosphate fluoride gels has been clinically documented, the 2% neutral NaF gel has not been adequately tested, and further clinical verification is needed. Daily use of a self-applied fluoride gel is recommended for patients undergoing orthodontic treatment or to those affected with xerostomia as a result of disease or head and neck radiation therapy. The dental profession and the public should be well informed on the proper use of clinically proven products to achieve optimum effectiveness and minimize the risk of fluoride ingestion. PMID- 8500123 TI - Fluoride mouthrinses and fluoride varnishes. AB - The cariostatic efficacy of rinsing with a 0.05-0.2% neutral sodium fluoride solution has been clearly demonstrated, especially in supervised school-based programmes in moderate and high caries risk children. The cost-benefit effect, however, is questionable in populations with low caries prevalence, and fluoride rinsing programmes are gradually being replaced by more individual fluoride therapy comprising combinations of fluoride toothpastes, tablets, or varnishes. Fluoride varnishes were developed as individual alternatives to conventional topical fluoride application and are today gaining acceptance for clinical application. Two varnishes, Duraphat containing 5% wt NaF and Fluor Protector with 0.9% wt fluor silane, are available commercially. The clinical effects seem to depend mainly on application frequency, especially in high caries risk groups. The cost-benefit effect is high, but can be increased by delegating application to auxiliary personnel in conjunction with regular dental visits. Toxicologically both fluoride mouthrinses and fluoride varnishes are safe if used as directed. PMID- 8500124 TI - Slow-release fluoride. AB - The latest evidence supports the concept of frequent applications of relatively low concentrations of fluoride for the elimination of caries, even in situations of high caries challenge. Dental materials exhibit a 'burst effect', and the fluoride release is short-lived. Intra-oral devices in the form of copolymer membranes or glass devices cause an elevation of salivary F levels for up to 2 years in animals and humans and have led to increased F uptake in enamel. Caries reduction has been achieved in rats using the copolymer device, and, at present, human caries trials using the copolymer and glass devices are under way in the USA and Leeds, respectively. These intra-oral devices hold great promise to target financial resources for prevention in groups of the population with high caries levels, in particular low socio-economic groups including ethnic minorities and the handicapped. PMID- 8500125 TI - Diet counselling and behaviour change. AB - A number of questions related to oral as well as general health seem to be relevant to a discussion on development of counselling techniques aimed at changing various types of health-related behaviour in man, such as dietary habits, smoking, and alcohol use. This paper discusses dietary counselling and behaviour change in dental practice. PMID- 8500126 TI - Efficacy of sweeteners and sugar substitutes in caries prevention. AB - The caries-preventive efficacy of sweeteners and sugar substitutes is not clearly established on an epidemiological scale. A review of cariogenicity assessments in vitro and in vivo as well as of human clinical caries trials, however, clearly demonstrates that the replacement of sugar by such products has a caries preventive effect. The clinical relevance of some bacteriostatic and/or cariostatic properties ascribed to saccharin, aspartame, and xylitol remains to be corroborated. PMID- 8500127 TI - Relative consumption of sucrose and other sugars: has it been a factor in reduced caries experience? AB - This paper examines the impact on the development of caries, especially on the proximal and the free smooth surfaces, that follows the reduction in sucrose consumption and the increase in consumption of the monosaccharides in the United States and Great Britain. Laboratory evidence shows that sucrose has a special role in proximal- and smooth-surface caries because of its ability to produce extracellular polysaccharides with the mutans streptococci, thus increasing plaque's ability to adhere to the enamel surface. Evidence from human studies, however, is less clear about the relative cariogenicity of the various sugars, possibly because experimental conditions are difficult to maintain in such studies. In the USA sucrose consumption has been diminishing for some year and is now only 47% of the total sugar consumption of 61 kg per person annually. The change in Britain has been less pronounced, sucrose there in 1984 constituted 83% of total consumption of 47.9 kg per person. Sucrose consumption in Britain is, therefore, higher than in the United States, even though the average total consumption of all sugars is higher in the USA. Limited data suggest that proximal- and smooth-surface lesions also constitute a higher proportion of caries incidence in Britain than in USA, and a cause-and-effect hypothesis between these factors is explored. Dietary education for oral health should harmonize with that for general health by emphasizing sensible food choices, which generally means selection of low-fat, low-sugar foods. PMID- 8500128 TI - Extrinsic and intrinsic sugars: a review of recent UK recommendations on diet and caries. AB - Development of caries in man is associated with dietary sugars, but the relationship between sugar contents of individual foods and their cariogenic potential is unclear. A recent report categorized dietary sugars as intrinsic (mainly fruit and vegetable) and extrinsic (mainly added sugars, milk, and fruit juices) and concluded that consumption of extrinsic sugars (except milk) should be replaced with that of intrinsic sugars. This paper examines briefly the dental consequences of the recommendations. PMID- 8500129 TI - Salivary counts of mutans streptococci and lactobacilli and past caries experience in caries prediction. AB - Clinical and salivary factors were compared with each other for the ability to predict 3-year caries increment in a group of 122 teenagers. The group was screened according to two levels of salivary mutans streptococci and lactobacilli and comparable levels of baseline caries experience (DFS). The risk for caries was validated at three different levels. Sensitivity, specificity, and the positive and negative prediction values were calculated for each level. The results showed that the baseline caries experience was better or as powerful as the salivary tests in predicting future caries increment at comparable screening and validation levels. PMID- 8500130 TI - Antimicrobial strategies in the prevention of dental caries. AB - Antimicrobial agents, applied either professionally or delivered from dentifrices or mouthwashes, could reduce caries by controlling plaque formation, suppressing cariogenic species, or by inhibiting bacterial metabolism. Chlorhexidine has proven anticaries activity; other agents might also prevent caries by means of their antiplaque properties. Sugar substitutes stabilize the microflora by reducing the number of acid challenges to plaque and stimulating saliva flow; some also have antimicrobial properties, especially against mutans streptococci. Vaccines have been prepared from purified antigens of mutans streptococci. These vaccines confer protection in non-human primates, but have yet to be tested in a human clinical trial. PMID- 8500131 TI - Sealants revisted: an update of the effectiveness of pit-and-fissure sealants. AB - The first sealant clinical trials used cyanoacrylate-based materials. These were replaced by dimethacrylate-based products which were marketed. A major difference between marketed sealants is their method of polymerization. First-generation sealants were initiated by ultraviolet light, second-generation sealants are autopolymerized, and third-generation sealants use visible light. Over time, clinical retention was found to be greater for second generation as compared with first-generation sealants. Five to 7 years after initial application the pits and fissures of approximately one third of teeth treated with first-generation sealants were fully protected as compared with two thirds of the teeth treated with second-generation sealants. First-generation, ultraviolet light initiated, sealants are no longer marketed. Clinical reports indicate that retention is similar for second- and third-generation systems, but longer clinical evaluations are necessary. A recent innovation is the addition of fluoride to sealants. Fluoride release to the saliva from a fluoride sealant system is rapid, but clinical studies are needed to determine if the fluoride addition improves caries inhibition. PMID- 8500132 TI - Integrated caries prevention: effect of a needs-related preventive program on dental caries in children. County of Varmland, Sweden: results after 12 years. AB - Twenty years ago the caries prevalence in Swedish children was among the highest in the world; within Sweden, it was highest in the County of Varmland. Ongoing clinical research projects were initiated to evaluate the separate and combined effects of preventive measures, and in 1978 a preventive program, based on caries risk assessment, was introduced for 3- to 19-year-olds in the county. The effects were monitored by a computerized epidemiological system. From 1979 to 1991, caries prevalence and incidence decreased by 75-90 and 75-85%, respectively. The percentage of caries-free 3-year-old children increased from 51 to 94%, and in 12 year-old children, the caries prevalence decreased from 6.5 to 1.0 DFS, the lowest in Sweden. The program is very cost-effective, and in 1990 the mean annual treatment time per child was the lowest in Sweden. Currently, new methods of caries risk prediction and integrated caries prevention are being developed, with special reference to cost-effectiveness. PMID- 8500133 TI - Systemic fluorides: drops and tablets. AB - Fluoride drops and tablets are effective caries-inhibiting agents which exercise their benefit through mainly topical means. Results of caries trials in which drops or tablets were used in the home vary from excellent to poor, depending on the compliance rates of both parents and offspring. Delivery in schools has also produced reductions of > 80%, and as poor as 20%, again possibly dependent on teacher vigilance. The pre-natal controversy re fluoride tablet benefits has only recently been tested under a true double-blind protocol and resulted in a non significant effect, although the trend was in favour of those whose mothers had taken F- tablets during pregnancy. Hence, while at the individual level, the slow intra-oral dissolution of fluoride tablets can be of great benefit for coronal caries in children, adolescents, and possibly medically compromised adults (with or without root caries), their contribution on a community basis cannot readily be compared with that of water or salt fluoridation. Although fluoride tablets have been held responsible for an increase in fluorosis prevalence, data which were assessed blind now exist to show that a daily dosage of 0.25 mg fluoride from birth is not associated with dental fluorosis, if additional fluoride products are not used injudiciously over the same period. PMID- 8500134 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8500135 TI - Intracellular calcium mobilization by inositol 1,4,5-trisphosphate: intracellular movements and compartmentalization. AB - Intracellular calcium ion (Ca2+) changes in NIH-3T3 fibroblasts responding to inositol 1,4,5-trisphosphate (IP3) injections have been monitored using high resolution digital imaging of the calcium indicator Fura-2. Ester loaded and microinjected indicator report radically different patterns of Ca2+ change during the IP3 response. These differences arise from intracellular compartmentalization of the ester loaded indicator which can seriously distort reported Ca2+ levels. Prominent among these aberrant responses is a signal in which Ca2+ levels in the cell nucleus appear to exceed those in the rest of the cell, and an apparent slowing of the Ca2+ recovery time-course throughout the cell when temperature is increased. Similar behavior is observed in other cell types. Judicious use of both loading techniques can provide information on Ca2+ movements into organelles that might otherwise escape detection. The Ca2+ rise normally measured in bulk or integrated single cell measurements is a complex mix of cytosol/nucleus and organellar changes. Much, if not all, of the observable organellar change is an accumulation, not release, of Ca2+ following the IP3 injection. The Golgi apparatus is a conspicuous early site for this accumulation, and mitochondria show a large, temperature sensitive uptake that is capable of limiting the maximal Ca2+ change during the response. PMID- 8500136 TI - Thimerosal induced changes of intracellular calcium in human endothelial cells. AB - We have measured the effects of the -SH oxidizing agent thimerosal on the intracellular calcium concentration in single endothelial cells from human umbilical cord vein. Application of 1 microM thimerosal after a 10 s prepulse of 10 microM evoked oscillations of intracellular calcium. Concentrations higher than 10 microM induced a few oscillations which were followed by a long lasting increase in intracellular calcium between 120 and 980 nM at 10 microM thimerosal, between 250 and 1290 nM at 100 microM. The plateau level of the thimerosal induced increase in intracellular calcium depended on the extracellular calcium concentration, and was clearly decreased in calcium free solution. It was also reduced if the extracellular potassium concentration was increased to 140 mM. Nickel (5 mM) did not block the elevation of intracellular calcium. Thimerosal induced quenching of the Fura-2 fluorescence in Ca2+ free solutions containing 1 mM Mn2+. These effects indicate that thimerosal opens a pathway for Ca2+ entry from the extracellular side. The amount of calcium which could be released by histamine was drastically reduced after initiation of the thimerosal response. If refilling of Ca2+ stores was prevented by incubation of the cells in Ca2+ free solution, histamine still induced a transient, but not maintained, increase in [Ca2+]i. After application of thimerosal in Ca2+ free solutions to prevent refilling of the stores, a transient increase in [Ca2+]i could still be recorded but the histamine response on [Ca2+]i almost disappeared indicating a discharge of Ca2+ stores by thimerosal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500137 TI - Calcium mobilization and cell proliferation activated by extracellular ATP in human ovarian tumour cells. AB - The effects of ATP on cell proliferation and intracellular calcium concentration ([Ca2+]i) were examined in a human ovarian cancer cell line (OVCAR-3). Micromolar concentrations of ATP promoted a biphasic rise in [Ca2+]i representing a phase with a rapid peak followed by a phase in which the rise was slower and sustained. When the influx of extracellular calcium was blocked by calcium chelation to EGTA, the ATP stimulated rise in [Ca2+]i was rapid and monophasic. Voltage sensitive calcium channel blockers like nifedipine and verapamil had no effect on the action of ATP while prenylamine totally blocked calcium influx. ATP inclusion in the medium significantly stimulated growth of OVCAR-3 cells. Fetal calf serum (FCS) increased [Ca2+]i with similar biphasic kinetics representing both the entry of extracellular calcium and release of calcium from intracellular stores. FCS also caused a substantial increase in cell growth. From these experiments it was concluded that an increase in [Ca2+]i is obligatory for stimulation of cell growth in OVCAR-3 cells and that this increase probably requires a contribution from the entry of extracellular calcium. The involvement of both pertussis toxin sensitive G-protein and protein kinase C in ATP induced responses was indicated by the data showing interference of the response by pertussis toxin and phorbol myristate acetate. PMID- 8500138 TI - Characterization of Ca2+ signals generated by extracellular nucleotides in supporting cells of the organ of Corti. AB - ATP has been demonstrated to act as a co-transmitter or neuromodulator in various physiological processes. There is recent evidence that ATP receptors, characterized as P2 purinergic receptors, are expressed in the sensory hair cells of the auditory organ. The aim of the present study was to know whether other cell types of the organ of Corti, the supporting cells, were also sensitive to external ATP. In both types of supporting cells considered in this study, Deiters' cells (DCs) and Hensen's cells (HEs), extracellular ATP at sub micromolar concentrations evoked a transient increase in [Ca2+]i as monitored with fluorescence microscopy using the calcium probe Indo-1. An apparent Kd of 0.5 and 0.9 microM was determined for DCs and HEs, respectively. Furthermore, we demonstrated that ATP stimulated Ca2+ release from internal stores in DCs, but not in HEs. Dynamic calcium imaging by confocal laser scanning microscopy of ATP induced Ca2+ mobilization demonstrated a calcium wave propagation in the cell body of DCs which originated in the phalangeal processes, suggesting a functional organization of Ca2+ sequestering stores in DCs. PMID- 8500139 TI - Classification of headache: methods and empirical data. Satellite meeting of the VIth International Headache Society Congress. Washington, D.C., 29 June 1992. Proceedings. PMID- 8500140 TI - The Ad Hoc Committee on Headache Classification. PMID- 8500141 TI - Headache classification: status praesens. PMID- 8500142 TI - Diagnosing migraine: are the criteria valid or invalid? AB - Making a clinical diagnosis is a thought process but we do not know how we remember, let alone think. Migraine attacks are dynamic, with symptoms evolving, progressing and regressing during 4-72 h. Some of us attempt to abstract criteria from this "drama", others try to see the whole "play" as a stage performance. However, we are dependent on patients' descriptions and must carefully evaluate the responses to our questions. Describing pain quality--translating feelings into words--is especially difficult. Patients can be led or misled by questions, particularly if posed by insensitive questionnaires applying rigid criteria. Nevertheless, criteria are essential for the inclusion or exclusion of patients in drug trials or a series when special investigations are being conducted, but not in a difficult diagnostic case when there are two concomitant headaches or when trying to help someone cope with migraine. PMID- 8500143 TI - The need for interaction between the "top-down" and "bottom-up" approaches to migraine. PMID- 8500144 TI - Reliability in headache diagnosis. AB - The reliability of headache diagnosis using the criteria of the International Headache Society (IHS) has not been well studied. One definition of reliability refers to the reproducibility of diagnoses assigned to the same individual at different times. Reproducibility of diagnosis should be assessed using different clinicians at different times, with or without specific diagnostic instruments. A diagnosis may be unreliable because of variability in diagnostic criteria, in the clinical information used to assign diagnoses, or in the interpretation and application of clinical information to a given set of diagnostic criteria. Reliable diagnostic methods are essential to the development of valid diagnostic methods, as well as for the identification of headache risk factors, biological markers, and effective treatments. An approach to studying the reliability of the International Headache Society criteria is outlined, modeled after the extensive studies conducted in the area of psychiatric diagnosis. PMID- 8500145 TI - Development of diagnostic criteria for headache syndromes: lessons from psychiatry. AB - This paper reviews the development of diagnostic criteria for the psychiatric disorders in order to provide a model for the development of classification of headache. The strengths and weaknesses of the current psychiatric classification system, and procedures that have been instituted to strengthen the next version of the classification are described. The problems that characterized the successive versions of the criteria are highlighted in order to stimulate future developments of diagnostic criteria for headache syndromes. Recommendations for application of these principles to headache classification are presented. PMID- 8500146 TI - Migraine headache: epidemiology and health care utilization. AB - Population-based studies of headache can help inform the development of diagnostic criteria. In population-based studies, migraine has been consistently revealed as a common disabling condition that affects males and females of all ages. From data obtained in a national survey of the United States population, we show that the prevalence of migraine and the frequency of attacks increase as household income decreases. Disability from attacks is not related to income. In contrast, physician diagnosis is more likely as household income increases. Moreover, physician diagnosis is more likely among females, older cases, those more likely to experience disability, and migraine sufferers reporting nausea (males), vomiting, and visual and sensory aura. Analysis of our data leads us to conclude that the symptoms most strongly associated with diagnosis may provide the greatest concern and interest on the part of physicians to make a diagnosis, even though other migraine-related symptoms are more common in the population and in clinical settings. Finally, among migraine sufferers with severe disability, a very large proportion do not receive the benefits of medical diagnosis and treatment. Though most migraine sufferers use OTC medications, given the frequency and associated disability of their migraine attacks, current therapy appears unsatisfactory. PMID- 8500147 TI - Validation of diagnostic criteria for migraine in the Zurich longitudinal cohort study. AB - This paper reports the results of a systematic assessment of the validity of the specific diagnostic criteria for migraine without aura, as defined by the International Headache Society (IHS), in a longitudinal epidemiologic sample of young adults who were selected from the general population of Zurich, Switzerland. Systematic modification of each of the IHS criteria for migraine without aura yielded one-year weighted prevalence rates ranging from 24% for the unmodified IHS criteria to 9% for the most restrictive definition of migraine. The major implications of the findings for the IHS criteria are: (a) they provide adequate coverage to classify the majority of subjects with headache in the general population; (b) there is little overlap between migraine and tension-type headache, suggesting that the criteria define moderately independent subgroups; (c) the criteria for migraine without aura appear to be too unrestrictive for application in the community, particularly among young adults at the peak period of incidence of migraine; (d) the criteria for "aura" need more precise operationalization; and (e) models of validation of the diagnostic criteria suggest that Criterion D of the IHS criteria for migraine without aura should be modified to require both gastrointestinal symptoms and photophobia and phonophobia. PMID- 8500148 TI - Classification of headache: methods and empirical data. Background and introduction. PMID- 8500149 TI - Diagnostic screen for assessment of the IHS criteria for migraine by general practitioners. AB - This study examines the sensitivity and specificity of a self-report screen for the diagnosis of migraine according to the IHS criteria in a sample of 1049 employees of the French National Railways. The diagnosis of migraine derived from the self-report instrument was compared to an unstructured diagnostic interview conducted by a neurologist specialized in the diagnosis and treatment of headache. The sensitivity of the diagnostic screen was poor, but the specificity was excellent. Optimal cut-off points for the questionnaire were determined by the Receiver Operator Characteristics (ROC) method. Assessment of the specific IHS criteria for migraine revealed that the following criteria failed to discriminate subjects with migraine from non-cases: "aggravation by physical activity" and "photophobia and phonophobia". Implications of the findings for modification of the IHS criteria were discussed. PMID- 8500150 TI - Evaluation of the nosology of chronic tension-type headache. AB - Tension-type headache is one of the problematic classes of the IHS classification of headache. Based on the data of 211 cases of chronic tension-type headache modified criteria are proposed for the diagnosis of chronic tension-type headache. In order to provide optimal discrimination between migraine and tension type headache it is recommended that the severity of characteristic migraine symptoms, which also frequently occur at a mild level of intensity among patients with tension-type headache, be incorporated into the diagnostic criteria for this headache. Specifically, mild photophobia and phonophobia, and headache aggravation by physical activity should not be used as exclusion criteria for tension-type headache. PMID- 8500151 TI - A headache clinic-based approach to field trials of the International Headache Society criteria. AB - Criteria for the diagnosis of headache disorders have recently been developed but require empirical validation. We present an approach to the evaluation of headache criteria in a headache clinic: define the group of headache sufferers to be studied, obtain data used in establishing the diagnosis, apply the diagnostic criteria and assess their usefulness. In applying this method to a group of patients with chronic daily headache, we found that approximately one-third would not fit the current criteria for chronic tension-type headache. We conclude that empiric validation of headache criteria based on subjective data is a complex and iterative process. Operational criteria for headache diagnosis to be used by primary care physicians should be validated in that setting and ideally should be relatively simple. PMID- 8500152 TI - Chronic daily headache. PMID- 8500153 TI - A personal view of the classification and definition of drug dependence headache. AB - A review of the literature indicates that drug-induced headache exists. The criteria of the International Headache Society proposed for the diagnosis of "headache induced by chronic substance use or exposure", however, need to be modified in order to identify all patients with this headache form. PMID- 8500154 TI - An epidemiological approach to the nosography of chronic daily headache. AB - Chronic daily headache (CDH), a heterogeneous group of headaches, includes different forms that occur daily, or almost daily, over a prolonged period of time. The nosography of this group is still a matter of debate, and in the most recent classification of the IHS (1988) only a few types of CDH are included: chronic tension-type headache, coexisting migraine. This study is an epidemiological approach to identifying the clinical features of CDH and the possible factors involved in changing episodic headache in CDH. Ninety CDH outpatients were investigated using a computerized record chart. The main observed forms were: (a) chronic tension-type headache--migraine with interparoxysmal headache, an evolved form of migraine in which a constant low severity headache develops between attacks; (b) transformed migraine, an evolved form of migraine with progressive worsening of the disease which reaches the level of continuous pain with the disappearance of typical migraine attacks. Interval headaches in migraine with interparoxysmal headache partly fulfil the IHS criteria for chronic tension-type headache. Analgesic drug abuse plays a prominent role in inducing CDH and in determining its clinical features. PMID- 8500155 TI - Transformed migraine. AB - Chronic tension-type headache, which is included in the International Headache Classification, is present in only a minority of patients who present with chronic daily headache. The majority have what is termed transformed migraine, with a history of distinct episodes of migraine in the initial years which progresses into chronic daily headache. These patients with transformed migraine exhibit mixed features of migraine and chronic tension-type headache. Two distinct types of transformed migraine are identifiable, namely those related to excessive intake of medications (drug-induced transformed migraine) and those unrelated to excessive use of medications. The clinical features of transformed migraine and the drug-induced variety are described. The need for revision of the International Classification to include chronic daily headache and the subtypes of transformed migraine is pointed out. PMID- 8500156 TI - Headache classification prior to the Ad Hoc criteria. PMID- 8500157 TI - Summary and recommendations for classification of headache. PMID- 8500158 TI - IHS Classification: present and future. PMID- 8500159 TI - The centromere frontier: kinetochore components, microtubule-based motility, and the CEN-value paradox. PMID- 8500160 TI - Through thick and thin: wasting, obesity, and TNF alpha. PMID- 8500161 TI - A putative modular domain present in diverse signaling proteins. PMID- 8500162 TI - Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos. AB - Xotch is a Xenopus homolog of Notch, a receptor involved in cell fate decisions in Drosophila. Using an extracellular deletion construct, Xotch delta E, we show that Xotch has a similar role in Xenopus embryos. Broad expression causes the loss of dorsal structures and the expansion and disorganization of the brain. Single blastomere injections of Xotch delta E induce autonomous neural and mesodermal hypertrophy, even in the absence of cell division. Xotch delta E inhibits the early expression of epidermal and neural crest markers yet enhances and extends the response of animal caps to mesodermal and neural induction. Our data suggest a mechanism for the function of Notch homologs in which they delay differentiation and leave undetermined cells competent to respond to later inductive signals. PMID- 8500163 TI - Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate. AB - The identity of cell types generated along the dorsoventral axis of the neural tube depends on inductive signals that derive from both mesodermal and neural cells. To define the nature of these signals, we have analyzed the differentiation of cells in neural plate explants. Motor neurons and neural crest cells differentiate in vitro from appropriate regions of the neural plate, indicating that the specification of cell fate along the dorsoventral axis of the neural tube begins at the neural plate stage. Motor neuron differentiation can be induced by a diffusible factor that derives initially from the notochord and later from floor plate cells. By contrast, floor plate induction requires contact with the notochord. Thus, the identity and patterning of neural cell types appear to involve distinct contact-mediated and diffusible signals from the notochord and floor plate. PMID- 8500164 TI - Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized. PMID- 8500165 TI - Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. AB - The epidermis is believed to contain two types of proliferating cells: stem cells and cells with a lower capacity for self-renewal and higher probability of undergoing terminal differentiation (transit amplifying cells). We report that keratinocytes with characteristics of stem cells can be isolated from cultured human epidermis on the basis of high surface expression of beta 1 integrins and rapid adhesion to extracellular matrix (ECM) proteins. Among keratinocytes there was a log linear relationship between the relative level of beta 1 integrins on the cell surface and proliferative capacity; furthermore, the cells with the highest colony-forming efficiency adhered most rapidly to type IV collagen, fibronectin, or keratinocyte ECM. Proliferating keratinocytes that adhered more slowly had characteristics of transit amplifying cells: after one to five rounds of division, all of their daughters underwent terminal differentiation. Since stem cells can be isolated to greater than 90% purity on the basis of their adhesive properties, it will now be possible to investigate the mechanisms that regulate the fate of their progeny. PMID- 8500166 TI - Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. AB - With the aim of identifying novel regulators of adipocyte differentiation, we have cloned and characterized preadipocyte factor 1 (pref-1), a novel member of the epidermal growth factor (EGF)-like family of proteins. Pref-1 is synthesized as a transmembrane protein with six tandem EGF-like repeats. In preadipocytes, multiple discrete forms of pref-1 protein of 45-60 kd are present, owing in part to N-linked glycosylation. While pref-1 mRNA is abundant in preadipocytes, its expression is completely abolished during differentiation of 3T3-L1 preadipocytes to adipocytes. Moreover, constitutive expression of pref-1 in preadipocytes, which in effect blocks its down-regulation, drastically inhibits adipose differentiation. This indicates that pref-1 functions as a negative regulator of adipocyte differentiation, possibly in a manner analogous to EGF-like proteins that govern cell fate decisions in invertebrates. PMID- 8500167 TI - Bos1p, an integral membrane protein of the endoplasmic reticulum to Golgi transport vesicles, is required for their fusion competence. AB - BOS1 encodes an integral endoplasmic reticulum (ER) membrane protein and genetically interacts with three other yeast genes (BET1, SEC22, and YPT1) whose products are required for membrane traffic between the ER and the Golgi apparatus. Using an assay that reconstitutes transport at this stage of the pathway, we find that anti-Bos1p antibody blocks protein export after vesicles bud from the ER but prior to fusion with the Golgi. Additionally, the depletion of Bos1p from the ER leads to the formation of transport-incompetent vesicles. Carrier vesicles, immunoisolated with anti-Bos1p antibody, are approximately 50 nm in size. These vesicles contain Bos1p, Sec22p, and Ypt1p, but not Bet1p. The functional interactions of Bos1p with Ypt1p and Sec22p may be necessary for the fusion competence of the ER to Golgi transport vesicles. PMID- 8500168 TI - FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. AB - Alpha factor induces arrest of yeast a cells in G1 and transcription of genes involved in mating. Prior work indicates that FUS3, a member of the MAP kinase family, and FAR1, whose molecular activity is unknown, contribute to cell cycle arrest by inhibiting G1 cyclins. Here we show that FAR1 is a substrate for FUS3 and that this phosphorylation regulates association of FAR1 with CDC28-CLN2 kinase. We show also that FAR1 is phosphorylated in vitro by the CDC28-CLN2 complex and in vivo in a CDC28-dependent manner. Mutational analysis of FAR1 reveals a correlation between its ability to associate with CDC28-CLN2 and to arrest the cell cycle. These results suggest that FAR1 protein is the link between the signaling pathway and the cell cycle machinery. PMID- 8500169 TI - Identification of essential components of the S. cerevisiae kinetochore. AB - We have designed and utilized two in vivo assays of kinetochore integrity in S. cerevisiae. One assay detects relaxation of a transcription block formed at centromeres; the other detects an increase in the mitotic stability of a dicentric test chromosome. ctf13-30 and ctf14-42 were identified as putative kinetochore mutants by both assays. CTF14 is identical to NDC10/CBF2, a recently identified essential gene that encodes a 110 kd kinetochore component. CTF13 is an essential gene that encodes a predicted 478 amino acid protein with no homology to known proteins. ctf13 mutants missegregate chromosomes at permissive temperature and transiently arrest at nonpermissive temperature as large-budded cells with a G2 DNA content and a short spindle. Antibodies recognizing epitope tagged CTF13 protein decrease the electrophoretic mobility of a CEN DNA-protein complex formed in vitro. Together, the genetic and biochemical data indicate that CTF13 is an essential kinetochore protein. PMID- 8500170 TI - Nucleosomal organization of telomere-specific chromatin in rat. AB - Rat liver interphase chromosomes have telomeres 20-100 kb in length. Micrococcal nuclease digestion of nuclei cleaves telomeres with a uniform 157 bp periodicity, producing soluble particles that sediment in sucrose gradients exactly like oligonucleosomes. The monomeric telomere particles comigrate with nucleosome core particles on nucleoprotein and DNA gels but do not bind H1. DNAase I cleaves telomere nucleoprotein into a series of bands spaced by about 10.4 bp and with the same intensity distribution as bands from bulk nucleosomes. Removal of H1 from chromatin alters the sedimentation properties of telomeres in parallel with bulk chromatin. Thus, telomeres of mammals are constructed of closely spaced nucleosomes, in contrast with the telomeres of lower eukaryotes, which show no evidence of nucleosomal structure. PMID- 8500171 TI - Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA. AB - Cauliflower mosaic virus 35S RNA contains a 600 nt leader with several small open reading frames that by themselves inhibit translation of downstream coding regions. In the context of the whole leader and in certain plant cells, however, translation of downstream coding regions is allowed. This translation is dependent on the RNA 5' terminus and other elements of the leader. However, its central portion is dispensable or can be modified by insertion of an energy-rich stem-loop structure or long coding region with many internal AUG codons. We conclude that this region can be by-passed (shunted) by the scanning complex. Shunting was also observed in trans between two separate RNA molecules. PMID- 8500172 TI - 3' splice site recognition in S. cerevisiae does not require base pairing with U1 snRNA. AB - The conserved nucleotides 9 and 10 of U1 small nuclear RNA (snRNA) have been proposed to base pair with either 5' exon or 3' splice site sequences. In S. pombe, U1 snRNA pairing with the conserved 3' splice site is required for the first step of splicing and viability. In contrast, we show that S. cerevisiae U1 mutants at positions 9 and 10 are fully functional. Splicing of several genes is normal in these strains, ruling out an essential base pairing between U1 snRNA and 3' splice sites. U1 snRNA positions 9 and 10 are shown to be involved in 5' splice site selection through their interaction with exon sequences. Our results demonstrate that some snRNA-pre-mRNA interactions are not evolutionarily conserved and that 3' splice site recognition occurs by different mechanisms in various organisms. PMID- 8500173 TI - A spring-loaded mechanism for the conformational change of influenza hemagglutinin. AB - Influenza hemagglutinin (HA) undergoes a conformational change that induces viral fusion with the cellular membrane. The structure of HA in the fusogenic state is unknown. We have identified a sequence in HA that has a high propensity for forming a coiled coil. Surprisingly, this sequence corresponds to a loop region in the X-ray structure of native HA: the loop is followed by a three-stranded, coiled-coil stem. We find that a 36 residue peptide (LOOP-36), comprising the loop region and the first part of the stem, forms a three-stranded coiled coil. This coiled coil is extended and stabilized in a longer peptide, corresponding to LOOP-36 plus the residues of a preceding, short alpha helix. These findings lead to a model for the fusogenic conformation of HA: the coiled-coil stem of the native state extends, relocating the hydrophobic fusion peptide, by 100 A, toward the target membrane. PMID- 8500174 TI - Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus. AB - Mice deficient in the gene encoding the peptide transporter associated with antigen processing (TAP1) have drastically reduced levels of surface expression of MHC class I molecules and few CD8+ T cells. Addition of class I binding peptides to cultured fetal thymi from TAP1 mutant mice invariably allowed the rescue of class I expression, while only some of these peptides promoted the positive selection of CD8+ T cells, which were polyclonal and specific for the peptide-MHC complex. A nonselecting peptide was converted to a mixture of selecting peptides when the residues involved in the interaction with TCRs were altered. A mixture of self-peptides derived from C57BL/6 thymi induced positive selection of CD8+ T cells at concentrations that gave relatively low class I surface expression. The implication of these observations is that self-peptides determine, in part, the repertoire of specificities exhibited by CD8+ T cells. PMID- 8500175 TI - Harrison Echols (1933-1993) PMID- 8500176 TI - Development and behavior in bacteria. PMID- 8500177 TI - RNA recognition: a family matter? PMID- 8500178 TI - Protein localization and asymmetry in the bacterial cell. PMID- 8500179 TI - How and why bacteria talk to each other. PMID- 8500180 TI - Signal transduction in the mammalian cell during bacterial attachment and entry. PMID- 8500181 TI - Prokaryotic plant parasites. PMID- 8500182 TI - Spatially localized rhomboid is required for establishment of the dorsal-ventral axis in Drosophila oogenesis. AB - The establishment of dorsal-ventral asymmetry of the Drosophila embryo requires a group of genes that act maternally. None of the previously identified dorsal ventral axis genes are known to produce asymmetrically localized gene products during oogenesis. We show that rhomboid (rho), a novel member of this group, encodes a protein that is localized on the apical surface of the dorsal-anterior follicle cells surrounding the oocyte. Loss of rho function causes ventralization of the eggshell and the embryo, whereas ectopic expression leads to dorsalization of both structures. Thus, spatially restricted rho is necessary and sufficient for dorsal-ventral axis formation. We propose, based on these observations and double mutant experiments, that the spatially restricted rho protein leads to selective activation of the epidermal growth factor receptor in the dorsal follicle cells and subsequently the specification of the dorsal follicle cells. PMID- 8500183 TI - Passover: a gene required for synaptic connectivity in the giant fiber system of Drosophila. AB - Passover (Pas) flies fail to jump in response to a light-off stimulus. The mutation disrupts specific synapses of the giant fibers (GFs), command neurons for this response. Pas was cloned from a P element-induced allele. The cDNA encodes a putative membrane protein of 361 amino acids. Null, hypomorphic, and dominant alleles were sequenced. In the adult central nervous system, and in the pupa during GF synapse formation, Pas is consistently expressed in the GF and in a large thoracic cell in the location of its postsynaptic targets. Pas establishes a new gene family. The Drosophila ogre protein, required for postembryonic neuroblast development, is 47% identical; the C. elegans Unc-7 protein, which when mutated alters the connectivity of a few neurons, is 33% identical. PMID- 8500184 TI - Lumenal proteins of the mammalian endoplasmic reticulum are required to complete protein translocation. AB - The role of the lumenal contents (reticuloplasm) of the endoplasmic reticulum (ER) in protein translocation was determined by in vitro analysis. Depletion of the reticuloplasm from mammalian rough microsomes revealed two distinct stages of the translocation reaction. The first stage, translocation up to and including signal peptide cleavage, was insensitive to the loss of the reticuloplasm, whereas the second stage, net transfer of the nascent chain into the ER lumen, was reticuloplasm dependent. In reticuloplasm-depleted membranes, signal-cleaved and glycosylated translocation intermediates were observed to transit free from the translocation channel to the cis, or cytoplasmic, side of the membrane. This translocation defect was complemented by reconstitution of lumenal proteins into depleted membranes. We propose that lumenal proteins are necessary for unidirectional protein translocation in mammalian ER. PMID- 8500185 TI - The binding of AP-1 clathrin adaptor particles to Golgi membranes requires ADP ribosylation factor, a small GTP-binding protein. AB - The small GTP-binding protein, ADP-ribosylation factor (ARF), has previously been shown to mediate the binding to Golgi membranes of the coatomer of non-cathrin coated (COP-coated) vesicles. We now report that ARF is also required for the binding of the AP-1 adaptor protein of clathrin-coated vesicles to Golgi membranes. The binding of coat proteins from both clathrin- and COP-coated vesicles requires an additional Golgi membrane-associated factor. These results suggest that a mechanistic similarity underlies diverse types of vesicle coats. PMID- 8500186 TI - Ultradian components of the sleep-wake cycle in babies. AB - Behavioral states may be analyzed as expressions of underlying cyclic activity involving several physiological systems. The human sleep-wake cycle in the first year of life shows, in addition to the establishment of circadian rhythmicity around the second month, the dynamics of its ultradian components, as can be seen in the more or less gradual decline of the polyphasic pattern. To detect these changes, we have analyzed the sleep-wake cycle of five babies of different ages (3, 4, 9, 11, and 13 months) observed for 5 consecutive days (Monday through Friday), 10 h (08:00-18:00 h) per day at a kindergarten by the first author, and during the night (18:00-08:00 h) by the parents. Behavioral observations were designed for minimizing interference with the babies' habits. Sleep/wake data were arranged in 60-min intervals, and the relative amount of time spent asleep per interval constituted the time series submitted for statistical analysis. The five resulting time series were submitted to spectral analysis for detecting the composition of frequencies contributing to the observed sleep/wake cycle. Several frequencies were thus obtained for each baby in the ultradian and circadian domain, ranging from one cycle in 2.0 h to one cycle in 24 h. The circadian component was the strongest rhythmic influence for all individuals except for the youngest (3-month-old) baby, who showed a semicircadian component as the main frequency in the power spectrum. Three individuals showed ultradian frequencies in the domain of 3-4 h. Differences in the spectra derive from three possible, and probably not exclusive, causes: 1) ontogenetic changes, 2) different masking effects, and 3) individual differences. PMID- 8500187 TI - Sleep inertia: best time not to wake up? AB - Sleep inertia is a brief period of inferior task performance and/or disorientation immediately after sudden awakening from sleep. Normally sleep inertia lasts < 5 min and has no serious impact on conducting routine jobs. This preliminary study examined whether there are best and worst times to wake up stemming from circadian effects on sleep inertia. Since the process of falling asleep is strongly influenced by circadian time, the reverse process of awakening could be similarly affected. A group of nine subjects stayed awake for a 64-h continuous work period, except for 20-min sleep periods (naps) every 6 h. Another group of 10 subjects stayed awake for 64 h without any sleep. The differences between these two groups in performance degradation are expected to show sleep inertia on the background of sleep deprivation. Sleep inertia was measured with Baddeley's logical reasoning task, which started within 1 min of awakening and lasted for 5 min. There appeared to be no specific circadian time when sleep inertia is either maximal or minimal. An extreme form of sleep inertia was observed, when the process of waking up during the period of the circadian body temperature trough became so traumatic that it created "sleep (nap) aversion." The findings lead to the conclusion that there are no advantages realized on sleep inertia by waking up from sleep at specific times of day. PMID- 8500188 TI - Circadian rhythm of blood pressure and heart rate in cardiopathic patients before and after heart transplantation. AB - The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitorings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24 h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation, the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation. PMID- 8500189 TI - Circadian time structure of cardiovascular characteristics in human pregnancy. AB - Conventional time-unspecified single measurements of blood pressure and heart rate may be misleading because they may be influenced, among other factors, by the patient's emotional state, position, diet, and external stimuli. All of these effects depend on the stages of a (mathematical) spectrum of rhythms and trends with age. The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) chronobiologic data processing, assesses early cardiovascular disease risk, e.g., in pregnancy. We have used this approach to quantify changes in 24-h synchronized (circadian) characteristics of cardiovascular variables in two consecutive pregnancies of a clinically healthy woman. Blood pressure and heart rate were automatically monitored, with few interruptions, at 1-h intervals, each time for at least 48 consecutive h, and for a total of 76 days of monitoring in each pregnancy. Circadian parameters of those circulatory variables were computed for each single day of measurement by the least-squares fit of a 24-h cosine curve. Regression analysis of parameters thus obtained revealed patterns of variation of circadian rhythm-adjusted means and amplitudes with gestational age. In both pregnancies, the predictable variability of the circadian-rhythm-adjusted mean of blood pressure can be approximated by a second-order polynomial model on gestational age: a steady linear decrease in systolic, diastolic, and mean arterial blood pressure up to the 22nd week of pregnancy is followed by an increase in blood pressure up to the day of delivery. This longitudinal study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure and heart rate and also allows the establishment of prediction and confidence limits for cardiovascular parameters in a healthy pregnancy. PMID- 8500190 TI - Pharmacokinetics of single-dose administration of naproxen at 10:00 and 22:00 hours. AB - The pharmacokinetics of naproxen was studied in 12 healthy male volunteers after a single oral dose of 500 mg at 10:00 and 22:00 h. Ingestion of drug at 22:00 h delayed the occurrence of peak serum levels (p < 0.0212). None of the other pharmacokinetic parameters exhibited any significant diurnal variations. PMID- 8500191 TI - Personal light dosimetry in permanent night and day workers. AB - Light exposure was measured in six day and six night watches (working 12-hour shifts five days in a row) during 48 h on work days and 48 h on days off using a photocell with a sensitivity corresponding to photopic vision. The photocell was mounted on a frame of spectacles, thus measuring in viewing direction. Light exposure was low both in night and day watches; however, in night watches exposures were significantly lower: On work days, night watches spent a mean of 13 min above 1,500 lx, day watches 52 min; on days off, night watches spent 3 min above 1,500 lx but day watches 89 min. Unexpectedly, night watches had no higher exposure during days off. We suspect that this is due to a light avoidance tendency in permanent night workers. High negative correlations between the acrophases of subjective state (e.g., alertness and mood) and light exposure in night watches indicate that bright light would probably increase desynchronization between subjective state, sleep, and activity. PMID- 8500192 TI - Circadian time-dependent kinetics of theophylline and its modulation by phenobarbital pretreatment in rats. AB - The pharmacokinetics of theophylline (TPH, 10 mg/kg i.v.) were assessed in rats (natural light-dark span, June 9-10) after i.p. pretreatment with saline and 80 mg/kg phenobarbital (PB), respectively, for 3 consecutive days at either 07:00 h or at 19:00 h. Serum concentrations of TPH were assayed by high-performance liquid chromatography. No significant differences of the elimination rates of TPH could be found between the times of TPH administration (clearance: 1.17 +/- 0.17 ml/kg/min at 07:00 h vs. 1.23 +/- 0.17 ml/kg/min at 19:00 hours). PB premedication markedly accelerated TPH elimination. The increase in clearance values was more expressed when TPH was injected at 07:00 h than at 19:00 h (2.48 +/- 0.67 vs. 2.06 +/- 0.41 ml/kg/min, p < 0.01). PMID- 8500193 TI - Adrenalectomy or superior cervical ganglionectomy modifies the nocturnal increase in rat pineal type II thyroxine 5'-deiodinase. AB - We studied the response of type II thyroxine 5'-deiodinase (5'-D) activity to superior cervical ganglionectomy (SCGX) or adrenalectomy (ADX) in the rat pineal gland and other tissues. The results show that no difference was found between controls and SCGX animals during the day, but at night, SCGX modified the day night cycle of 5'-D activity in the pineal gland. In the same way, ADX did not modify the enzyme activity during the day in pineal gland, harderian gland, hypophysis, or brain frontal cortex (BFC). However, in brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1 adrenergic stimulation by blood circulating catecholamines, 5'-D activity is significantly decreased. At the time point of maximal pineal 5'-D activity in controls (02:00 h), ADX animals did not exhibit the nocturnal increase of the enzyme activity that occurs with control rats. Moreover, at 04:00 h ADX did not show any effect on pineal 5'-D activity. These results seem to suggest that the presence of catecholamines in blood is necessary for the pineal 5'-D activity nocturnal increase, although it does not participate in regulating the basal enzyme activity during the day. PMID- 8500194 TI - Phase resetting of the human circadian pacemaker with use of a single pulse of bright light. AB - Since the initial studies reporting that light can alter the phase position of the human circadian system, there has been increasing interest in the use of bright light as a tool for manipulating the phase position of the circadian pacemaker. Exposure protocols typically require subjects to receive 2-5 h of exposure over several circadian cycles. As a consequence, bright light treatment can involve a considerable time investment. However, recent studies indicate that a single pulse of bright light can produce significant phase shifts in the circadian pacemaker. If a single pulse of bright light can produce significant phase-shifting effects, multiple-pulse designs may be unnecessary. This study examined the phase-shifting effects of a single 4-h pulse of bright light (12,000 lux) in 14 male and one female subject aged between 19-45 years. With use of a "constant routine" to estimate circadian phase, a single 4-h pulse of light produced significant shifts in the phase of the core temperature rhythm. The timing of the exposure, relative to the core temperature rhythm, determined the degree and direction of the phase shift. Exposure immediately prior to habitual bedtime produced a mean phase delay in the core temperature of 2.39 h (SD = 1.37 h). In contrast, exposure immediately following habitual wake-up produced a mean phase advance of 1.49 h (SD = 2.06 h). In addition, the magnitude of the shift increased the closer the light pulse was to the individual's estimated endogenous core temperature minimum. There was, however, considerable interindividual variability in this relationship.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500195 TI - Recognition of nucleic acid base by tryptophan-containing peptides: spectroscopic study on interaction of N-acetylTrp-(Gly)m-Asp-(Gly)n-TrpNHCH3 (m = 0-2, n = 0-2) with guanine base. AB - As part of the designs of tryptophan-containing peptides which possess specific binding ability for each nucleic acid base, a series of N-acetylTrp-(Gly)m-Asp (Gly)n-TrpNHCH3 (m = 0-2, n = 0-2) were chemically synthesized, and their abilities to form complexes with a guanine base were examined by the fluorescence and 1H-NMR methods. Fluorescence titration suggested the most preferential stacking interaction of the Trp-Gly-Asp-Trp sequence with the base. Analysis of low-field shifts of guanine N2-amino protons showed the hydrogen bond pairing with the Asp carboxyl side chain and its favorable formation for the -Gly-Asp-Trp peptide sequence. On the other hand, the largest up-field shift of guanine H8 proton was observed for Trp-Gly-Asp-Trp peptide, although its shifting degree caused by the stacking interaction with the Trp indole ring was not so significant. Thus, both spectroscopic methods indicated the Trp-Gly-Asp-Trp sequence to be most suitable for the guanine base recognition, which is constituted with the intimate cooperation of the hydrogen bond formation between the Asp carboxyl and guanine NH2 groups and the stacking interaction of the base with two neighboring Trp indole rings. This sequence preference would also be possible in acidic circumstances where the guanine N7 atom is protonated. A tentative interaction model is proposed based on these spectroscopic results. PMID- 8500196 TI - Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 1H- and 13C-nuclear magnetic resonance spectroscopy, and its enantioface-differentiating ability. AB - Analyses of the 1H- and 13C-nuclear magnetic resonance (1H- and 13C-NMR) spectra of the cyclooctapeptide cyclo (L-Phe-L-Pro-Gly-L-Pro)2 (3) in CDCl3 with the aid of the C-H correlated spectroscopy (C-H COSY) two-dimensional NMR spectrum (Fig. 2) suggested that two kinds of C2-symmetric conformation with all trans and cis trans-trans-trans forms coexist. When 0.5 eq of CsSCN or 1 eq of D- and L PheOMe.HCl (D/L ratio = 1/2) was added to a solution of the cyclooctapeptide (3) in CDCl3, the 1H- and 13C-NMR spectra (Fig. 3) suggested the presence of only one C2-symmetric conformation (all trans), resulting from the formation of complexes with CsSCN or D- and L-PheOMe.HCl. The 13C-NMR spectra of the complexes of the cyclooctapeptide (3 or 4) with D- and L-PheOMe.HCl displayed separate resonances for each carbon atom of D-PheOMe.HCl and L-PheOMe.HCl. Furthermore, the ability of 3 to distinguish the D from the L enantiomer, is superior to that of 4 (Table II). PMID- 8500197 TI - New fluorinated dopamine D2 ligands with benzofuran skeleton. The synthesis and in vitro evaluation. AB - New fluorinated ligands with N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,3 dihydrobenzofuran-7-carboxamide skeleton, which are useful as a prototype to develop 18F labelled in vivo radiotracer for positron emission tomography (PET), were synthesized, and their binding affinities for the dopamine D2 receptors were investigated. Fluorine atom was introduced at C-4 of the pyrrolidine ring (10) or at ethyl substituent at C-5 of the dihydrobenzofuran moiety (20). The in vitro IC50 values of these ligands for the dopamine D2 receptors which were determined by their ability to inhibit the binding of [3H]spiperone binding in rat striatal membrane were 17 and 36 nM, respectively. Thus, the fluorinated compounds 10 and 20 may be possible candidates for further in vivo investigation. PMID- 8500198 TI - Synthesis and antiinflammatory and analgesic properties of 2-amino-1H benzimidazole and 1,2-dihydro-2-iminocycloheptimidazole derivatives. AB - 2-Amino-1H-benzimidazoles (3) and 1,2-dihydro-2-iminocycloheptimidazoles (4) were synthesized and evaluated for antiinflammatory and analgesic activities. The compounds in the series 3 were synthesized via phenylthioureas (6) or 2-chloro-1H benzimidazole (12). Most of 4 were synthesized by two methods. One was the reaction of carbodiimides (14) with 2-amino-2,4,6-cycloheptatrien-1-one (method A). The other was the reaction of guanidines (15) with 2-chloro-2,4,6 cycloheptatrien-1-one (method B). Some of the compounds 3 and 4 exhibited potent antiinflammatory and analgesic activities when compared to timegadine (1) or tiaramide hydrochloride (HCl) (17). It was of interest that 1-(2-benzothiazolyl) 2-cyclohexylimino-1,2-dihydrocycloheptimid azole (4e) showed superior analgesic activity to timegadine or tiaramide HCl (ED50 = 1.7 mg/kg p.o. in the acetic acid induced writhing test, ED30 = 14.0 mg/kg p.o. in Randall-Selitto method) in spite of no effect on prostaglandin E2 synthesis. PMID- 8500199 TI - Chemical modification of an antitumor alkaloid, 20(S)-camptothecin: E-lactone ring-modified water-soluble derivatives of 7-ethylcamptothecin. AB - 7-Ethylcamptothecin (1d), a model which does not have any site on the A-ring for further modification was converted into water-soluble derivatives by opening the E-ring lactone. 1d was heated in N,N-dimethylenediamine to yield amide 2a, and this was then acylated to furnish 3a-q, which were soluble in water as their HCl salts. The propionyl (3b), butyryl (3c) and methylthiopropionyl (3h) derivatives showed higher activity than the sodium salt of 1d. The acyl group makes the derivatives more lipophilic, and ease of hydrolysis of amide 2a to 1d is thought to be necessary for significant activity. PMID- 8500200 TI - Methods of evaluation of release of carbon dioxide from effervescent suppositories. AB - Two different test methods were studied for the evaluation of release profiles of carbon dioxide, CO2, from effervescent suppositories. Three lots of commercial suppositories containing sodium bicarbonate and anhydrous sodium dihydrogen phosphate were used. The volume of CO2 released from these suppositories in normal saline with or without polysorbate 80 as a medium was measured with a gas burette. In the measurement performed using the apparatus without stirring, method 1, only 60% of CO2 was released from the suppositories in the medium without polysorbate 80. In this measurement, a native release profile was detected because the medium was not stirred. In the case with stirring, however, method 2, 100% was released from those suppositories in the medium containing 1% polysorbate 80 with comparatively low standard deviations. These findings indicate that method 1 is most beneficial for a test comparing the effects of various factors such as additives and melting points on the release profiles of CO2 from the effervescent suppositories. However, this method is not practical for quality control of formulations because of the incomplete release of CO2; method 2, in contrast, is useful because of its complete release and low standard deviations. These results suggest that methods 1 and 2 for release tests of CO2 are most applicable to the early and late formulation studies of effervescent suppositories, respectively. PMID- 8500201 TI - Synthesis, structure and antitumor activity of a new water-soluble platinum complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato(2-)-O2] platinum(II). AB - The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with 2,4 dioxopentanoic acid gave a water-soluble complex, (1R,2R-cyclohexanediamine N,N')[2-hydroxy-4-oxo-2-pentenoato (2-)-O2] platinum(II). The structure of the complex was determined by X-ray crystal analysis. The data indicated a chelation of the acetylacetonato part of 2,4-dioxo-pentanoic acid to platinum(II). The complex showed moderate antitumor activity against murine leukemia L1210 in mice (T/C = 195% at a dose of 200 mg/kg) and high activity against cisplatin-resistant L1210 leukemia (T/C = 275% at a dose of 25 mg/kg). PMID- 8500202 TI - Syntheses of 3-substituted 1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine 5,7(1H,6H)-diones (6-phenyl analogs of toxoflavin) and their 4-oxides, and evaluation of antimicrobial activity of toxoflavins and their analogs. AB - 6-Phenyl analogs of toxoflavin (1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine 5,7(1H,6H)-diones ) (7a--f) and their 4-oxides (8a-f) were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (6a-f) of 6-(1 methylhydrazino)-3-phenyluracil (5). Both sets of compounds, 7a-f and 8a-f, gave the corresponding 1-demethyl derivatives (10a-f) upon treatment with nucleophiles such as dimethylformamide (DMF) and acetic acid under heating. The activities of toxoflavins (1a-e), toxoflavin 4-oxides (3a-e) and their 6-phenyl analogs (7a-f and 8a-f) against a variety of bacterial and fungal strains were examined. Most of the compounds showed strong inhibitory activities against gram-positive bacteria. Among the compounds, 1c, 1d, 1e, and 3c exhibited the strongest inhibitions of Micrococcus lutea (0.5 micrograms/ml minimal growth-inhibitory concentration) and Staphylococcus aureus 4R (1 microgram/ml), as well as Bacillus subtilis and Staphylococcus aureus (1-2 micrograms/ml). Most of the compounds had strong antifungal activity (2-100 micrograms/ml minimal growth-inhibitory concentration) against Candida albicans and Saccharomyces cerevisiae. PMID- 8500203 TI - Evaluation of the final deprotection system for the solid-phase synthesis of Tyr(SO3H)-containing peptides with 9-fluorenylmethyloxycarbonyl (Fmoc)-strategy and its application to the synthesis of cholecystokinin (CCK)-12. AB - Acidolytic deprotection and cleavage conditions for an acid-labile Tyr(SO3H) containing peptide were systematically examined with respect to acid, temperature, and scavenger. The 90% aqueous trifluoroacetic acid (TFA)-based reagent systems (90% aqueous TFA/m-cresol and 90% aqueous TFA/m-cresol/2 methylindole) at 4 degrees C were found to minimize the deterioration of Tyr(SO3Na) in the peptide. The latter deprotection/cleavage system was applied to the 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase synthesis of cholecystokinin (CCK)-12 on an acid-labile PAL-linked support (PAL = peptide amide linker), with Fmoc-Tyr(SO3Na)-OH as a building block. PMID- 8500204 TI - Absolute configuration of L-methionine sulfoximine as a toxic principle in Cnestis palala (Lour.) Merr. AB - An unusual amino acid, L-methionine sulfoximine (1), has been isolated from the fresh seeds of Cnestis palala (Lour.) Merr. [Connaraceae]. The absolute configuration of the natural sulfoximine (1) was confirmed to be 2(S)-methionine S(S)-sulfoximine [(2S,SS)-2-amino-4-(S-methylsulfonimidoyl)-n-butanoic acid] by comparison of the [alpha]D value and IR spectrum with those of authentic samples obtained through the optical resolution of synthetic materials. Acute toxicity of the seeds of C. palala in a beagle dog was also studied. PMID- 8500205 TI - Application of the solid dispersion method to the controlled release of medicine. III. Control of the release of slightly water soluble medicine from solid dispersion granules. AB - In order to control the release rate of slightly water soluble medicine by using the solid dispersion (SD) method, the SD was prepared with a water soluble polymer and the slightly soluble medicine, and the medicine release from the solid dispersion granules was studied. The SD granules were prepared by the evaporation of ethanol after dissolving into ethanol a slightly water soluble medicine (flurbiprofen (FP)) and soluble polymers (hydroxypropyl cellulose (HPC)). HPC has four grades of molecular weight. The release rate of FP from SD was measured by the rotating basket method (JP XII). The release rate of FP from the SD granules was markedly larger than that from FP powder, and it was larger with a lower HPC molecular weight. It is speculated that these results were mainly based on the molecular dispersion state of FP and HPC in SD. PMID- 8500206 TI - Use of high performance liquid chromatography for increased assay sensitivity of beta-lactamase activity in bile. AB - A study to develop a sensitive method for measuring beta-lactamase activity in bile was conducted. Since separation of substrate from biological components is required to increase the assay sensitivity and to achieve an accurate assay of beta-lactamase activity, high performance liquid chromatography (HPLC) was used for separation and analysis of the substrates (cephaloridine for cephalosporinase, benzylpenicillin for penicillinase and cefuloxime for cefuloximase). In addition, conditions for increased assay sensitivity were also studied and optimal substrate concentrations and reaction times were determined. beta-Lactamase activity of 0.05 munit/ml in bile was detected using the HPLC assay method which is a significant improvement when compared to the direct spectrophotometric method which has a detection limit of approximately 10 munit/ml. PMID- 8500207 TI - Regional vs general anaesthesia in orthopaedics. PMID- 8500208 TI - New guidelines for preoperative fasting. PMID- 8500209 TI - Techniques for post-op pain management in the adult. AB - Nurse-administered analgesia is simple, universally accessible, and cost effective. This route of administration must be fully explored and exploited to gain maximal analgesia at minimal cost. Combined, balanced multimodal analgesia with NSAIDs and opioids used preoperatively to prevent pain should be encouraged. Intraoperative analgesia should not consist solely of opioids, but also local anaesthetics and NSAIDs. Postoperatively, balanced analgesia should continue and when the patient is able to tolerate fluids the oral route of administration should be used. The solution to improved postoperative analgesia lies in exploitation and liberalization of traditional analgesic drugs and techniques. We do not need new pharmacology or new technology. We need to use the drugs and techniques we already have in a much more effective and efficient fashion. Anaesthetists have been at the forefront of delivering superb analgesia to patients after extensive major surgical procedures using epidural analgesia and patient-controlled analgesia. We must focus on postoperative pain management of all patients to ensure that optimal analgesia is provided throughout the institution. This requires a multi-disciplinary team of health care professionals and a multi-modal array of analgesics. This approach represents a change from current practice. Considerable time and energy has been invested in the development of the clinical practice guidelines and they deserve our consideration as we manage patients now and in the future. PMID- 8500210 TI - Blunt thoracic trauma: anaesthesia, assessment and management. PMID- 8500211 TI - New inhalational agents--desflurane and sevoflurane. PMID- 8500212 TI - Practical CO2 monitoring in anaesthesia. PMID- 8500213 TI - Anaesthetists' role in neonatal resuscitation and care of the newborn. PMID- 8500214 TI - Anaesthesia for the aging patient. PMID- 8500215 TI - Fetal monitoring and anaesthesia for fetal distress. PMID- 8500216 TI - Oxygen transport. PMID- 8500217 TI - New iv induction anaesthetics. PMID- 8500218 TI - Pain control in the pediatric patient--the role of anaesthesia. PMID- 8500219 TI - Metabolic basis of the synergistic antitumor activities of 5-fluorouracil and cisplatin in rodent tumor models in vivo. AB - The biochemical mechanism of the synergy of 5-fluorouracil (FUra) and cisplatin (CDDP) was studied using transplantable tumors in rodents in vivo. The reduced folate 5,10-methylenetetrahydrofolate (CH2FH4) and its precursor tetrahydrofolate (FH4) are essential cofactors for the formation of a tight ternary complex of thymidylate synthase (TS) and 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) derived from FUra. Intraperitoneal administration of CDDP (5 mg/kg) inhibited the incorporation of exogenous L-methionine into ascitic tumor cells and increased the levels of CH2FH4 and FH4 in ascitic Yoshida sarcoma and P-388 cells transplanted into rats and mice to levels about 2-3 times those measured in cells from animals that were not treated with CDDP. Preincubation with 10(-6) M FUra in Hanks' medium inhibited [6-3H]-2'-deoxyuridine incorporation into DNA of tumor cells from CDDP-treated rats 3 times more than that into cells from untreated rats, indicating that the inhibition of TS by FdUMP derived from FUra was enhanced in the presence of CH2FH4. Intraperitoneal administration of CDDP on day 1 and continuous infusion of FUra from day 1 to day 6 had synergistic effects in inhibiting tumor growth in Yoshida sarcoma-bearing rats. Oral administration of UFT, a combined form of 1 M tegafur and 4 M uracil, for 7 consecutive days beginning at 24 h after tumor implantation and a single i.p. injection of CDDP on day 1 had a significantly greater effect than did either agent alone. These results suggest that CDDP significantly enhances FUra cytotoxicity by inhibiting intracellular L-methionine metabolism and consequently increasing the reduced folate pool in mammalian tumor models in vivo. PMID- 8500220 TI - Antitumor activity and cytotoxicity of a new ankinomycin derivative, 3'-,11 dibutyryl ankinomycin. AB - Ankinomycin is a new antitumor antibiotic found in the culture broth of Streptomyces sp. SF2587. Ankinomycin showed marked cytotoxicity and antitumor activity against some murine leukemias, but the activity against murine solid tumors was rather weak because of its strong acute toxicity. We synthesized ankinomycin acyl derivatives and examined their antitumor activity. Among the derivatives, 3',11-dibutyryl ankinomycin (AN1006) exhibited the highest antitumor activity. The antitumor activity of AN1006 was dependent on the administration schedule, and on the most effective schedule, AN1006 showed activity comparable with that of Adriamycin (ADM) against murine solid tumors and leukemias. AN1006 showed a cytotoxic spectrum different from that of ADM, exhibiting cytotoxicity stronger than that of ADM against colon carcinoma, stomach carcinoma, and some leukemia cell lines. According to these in vitro effects, AN1006 showed antitumor activity superior to and equal to that of ADM against human colon xenografts and stomach carcinoma xenografts in athymic nude mice, respectively. AN1006 was effective against multidrug-resistant tumors in vitro and in vivo. AN1006 is an interesting candidate for further evaluation. PMID- 8500221 TI - A slow-release methotrexate formulation for intrathecal chemotherapy. AB - Optimal anticancer treatment with cell cycle phase-specific antimetabolites requires a sustained maintenance of cytotoxic drug levels. However, drugs that can be administered intrathecally have short half-lives in cerebrospinal fluid (CSF) and require repeated administrations by lumbar punctures, which are painful and inconvenient. Implantable pumps are expensive and require surgery. In a rat model, a lipid-based formulation of methotrexate (Depo/methotrexate) was tested for extended maintenance of therapeutic CSF concentration after a single injection. The half-life of methotrexate in CSF after an intracisternal injection of Depo/methotrexate was 5.4 days compared to 0.30 days for unencapsulated methotrexate. This 18-fold increase in methotrexate half-life may make Depo/methotrexate useful for intrathecal chemotherapy of neoplastic meningitis. PMID- 8500222 TI - Enhancement of antitumor activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C. AB - UCN-01 (7-hydroxy-staurosporine) is a potent and selective inhibitor of protein kinase C (PKC), one of several protein kinases examined. UCN-01 itself was shown to exhibit antitumor activity in vitro and in vivo in oncogene-activated human and murine tumor cell lines. Since the mechanism(s) of action of UCN-01 is thought to be different from those of alkylating agents, including mitomycin C (MMC), we tested the combined effect of UCN-01 with MMC on human epidermoid carcinoma A431 cells. UCN-01 potentiated the antiproliferative activity of MMC and yet it did not affect the growth of the cells in vitro. However, other nonselective protein kinase inhibitors, such as staurosporine, K-252a, KT6124 (a derivative of K-252a) and H7, did not enhance the activity of MMC. Isobologram analysis revealed that the interaction of UCN-01 with MMC was synergistic in its antiproliferative activity. A DNA histogram of A431 cells treated with both UCN 01 and MMC showed a block in the cell cycle at the G1/S phase. However, a histogram of cells treated with UCN-01 or MMC alone showed a G1 or a G2M block, respectively. The combined effect of UCN-01 with MMC was further examined in vivo in xenografted A431 cells in nude mice. The combination of both drugs in a single i.v. injection exhibited greater antitumor activity than MMC and UCN-01 alone (P < 0.01). This synergistic antitumor effect was also confirmed in two other solid tumor cell lines, i.e. human xenografted colon carcinoma Co-3 and murine sarcoma 180. The same was observed in the i.v.-inoculated P388 leukemia model, in which we saw an increased lifespan of mice when UCN-01 was combined with MMC. These results suggests the feasibility of using UCN-01 in clinical oncology, especially in combination with alkylating agents such as MMC. In addition, this combination therapy might be a novel chemotherapeutic approach to MMC-insensitive tumors in clinical trials. PMID- 8500223 TI - Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles. AB - Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers. We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors. L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7. Mean particle size was 1.88 +/- 0.89 microns, and the entrapment efficiency was 93.08% +/- 2.96%. F-Ann was prepared as a suspension (particle size < or = 0.2 microns) in 10% DMSO. Drug levels were measured by fluorescence spectrometry after extraction with chloroform. The extraction ratio ranged between 60% and 90% for both drugs in most tissues. Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, sixfold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors. Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain. Heart AUCs were similar with all three drugs. Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX. The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system. The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated. PMID- 8500224 TI - Preclinical antitumor activity of orally administered platinum (IV) complexes. AB - Several novel platinum (IV) mixed ammine/amine dicarboxylate dichlorides of general structure [Pt(IV)Cl2(OCOY)2NH3(XNH2)], where Y is aliphatic or aromatic and X is alicyclic or aliphatic, known to be particularly well absorbed following oral administration, were evaluated by that route for their antitumor activity. Testing of the Pt(IV) derivatives took place concomitantly with i.v. administered cisplatin and carboplatin in two s.c. staged tumor models, the murine M5076 sarcoma and human A2780 ovarian carcinoma. Based upon repetitive experiments which included an evaluation of different vehicles and treatment schedules, each of the orally administered Pt(IV) dicarboxylates was reproducibly active in the M5076 tumor, producing mean maximum gross log cell kill (LCK) values of between 1.5 and 2.0, and lifespan increases, reflected by mean maximum treated/control median survival (T/C) values, of 139-151%. Cisplatin and carboplatin given i.v. yielded mean maximum LCK of 3.5 and 2.5, respectively, as well as mean maximum T/C values of 166% and 164%, respectively, in the same tumor model. The best of the derivatives in the M5076 experiments, JM-216 [ammine/cyclohexylamine diacetato dichloride Pt(IV)], produced LCK values that averaged only 0.5 lower than that of carboplatin, and increases in lifespan not significantly different than that of carboplatin. Against the A2780 tumor, the Pt(IV) dicarboxylates produced individual best effects of between 0.8-1.1 LCK, based on data from two or three experiments. The mean maximum LCK values for cisplatin and carboplatin were 1.8 and 2.2 LCK, respectively. JM-225, ammine/cyclopentylamine diacetato dichloride Pt(IV), was active in two of three experiments, including one result comparable to that of carboplatin. The Pt(IV) mixed ammine/amine dicarboxylate dichlorides represent a novel class of Pt derivative capable of expressing oral antitumor activity in both murine and human tumor models. PMID- 8500225 TI - Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach. AB - Ten patients with histologically documented peritoneal mesothelioma were treated with intraperitoneal cisplatin 200 mg/m2, sodium thiosulfate rescue and etoposide 65-290 mg/m2 every 4 weeks for a maximum of six cycles. All had epithelial or mixed epithelial-fibrous histology. Toxicity was tolerable, with 50% sustaining grade 3 or 4 granulocytopenia. There was one episode of neutropenic fever. Grade 2 peripheral neuropathy occurred in one patient, grade 1 in five patients. Complete remission occurred in one of five patients with measurable disease. Median survival for patients whose tumors were surgically debulked to < 2 cm residua prior to treatment was 22 months, while it was 5 months for those with measurable, surgically inaccessible disease (P = 0.0731 by Cox regression proportional hazard model). These data suggest that patients who present with resectable disease may benefit from an aggressive adjuvant approach. This possibility warrants prospective testing in a randomized clinical trial. PMID- 8500226 TI - Interactions of vinblastine and vincristine with methotrexate transport in isolated rat hepatocytes. AB - The accumulation of methotrexate (MTX) in the presence of vinblastine (VBL) and vincristine (VCR) was studied in isolated rat hepatocytes. In accordance with our recent study on vindesine (VDS), we found VBL and VCR to reduce net MTX accumulation significantly at 15 min after MTX addition. Drug concentrations of 100 microM VBL and 500 microM VCR led to 67% and 82% reductions in intracellular MTX, respectively. Since there was only a slight inhibition of MTX efflux by 100 microM VBL, the accumulation data demonstrate that the major effect of VBL is on MTX influx. Dixon-plot analyses are suggestive of competitive inhibition of the MTX influx, yielding inhibition constants (Ki values) of 55 microM for VBL and 110 microM for VCR. Since the Ki values correspond grossly to plasma levels obtained in humans shortly after the infusion of therapeutic doses of the vinca alkaloids studied herein, the interaction with MTX uptake could serve to diminish the toxicity of MTX to nonmalignant cells. PMID- 8500227 TI - Phase I trial of a 5-day infusion of L-leucovorin plus daily bolus 5-fluorouracil in patients with advanced gastrointestinal malignancies. AB - The combination of leucovorin [(6d,l)-5-formyl-tetrahydrofolate] and 5 fluorouracil (5-FU) has increased efficacy compared to 5-FU alone as treatment of advanced colorectal cancer. Leucovorin is metabolized to methylene tetrahydrofolate, which potentiates the antitumor actions of 5-FU by forming a ternary complex of thymidylate synthase, fluorodeoxyuridine and methylene tetrahydrofolate. Only l-leucovorin is metabolized to methylene tetrahydrofolate and forms this ternary complex. However, d-leucovorin may not be inert. d Leucovorin may impair cellular uptake and metabolism of l-leucovorin, thereby inhibiting the actions of l-leucovorin. Because of this possible limitation to the effectiveness of racemic leucovorin, we have begun to explore the effects of the pure, biologically active isomer, l-leucovorin. In this phase I trial, patients with advanced gastrointestinal malignancies were treated with a 5-day continuous infusion of l-leucovorin and daily intravenous boluses of 5-FU at 370 mg/m2. The dose of l-leucovorin was escalated in groups of three patients at four doses, 200 mg/m2 per day, 400 mg/m2 per day, 700 mg/m2 per day and 1000 mg/m2 per day. Treatment was repeated every 28 days. Seventeen patients with advanced gastrointestinal cancers entered the trial. Sixteen patients were evaluable for toxicity. Toxicity was similar to that expected for leucovorin plus 5-FU. The most common severe toxicities (and the number of patents affected) were: diarrhea (2), mucositis (2), nausea/vomiting (1), and abdominal/rectal pain (2). The maximum tolerated dose of l-leucovorin was 700 mg/m2 per day. Twelve patients were evaluable for response. One complete, one partial and one minor response were observed. All responses occurred among the nine patients with colorectal carcinomas. The combination of l-leucovorin and 5-FU is well tolerated by patients and appears active for treatment of advanced colorectal carcinomas. Additional clinical trials are necessary to determine if l-leucovorin is more effective than d,l-leucovorin for modulating the effectiveness of 5-FU. PMID- 8500228 TI - Effect of O6-benzylguanine on the response to 1,3-bis(2-chloroethyl)-1 nitrosourea in the Dunning R3327G model of prostatic cancer. AB - The DNA-repair protein O6-alkylguanine-DNA alkyltransferase is known to protect tumor cells from the antitumor effects of carmustine (BCNU). This repair protein was inactivated in Copenhagen rat prostate tumors by treatment with O6 benzylguanine in attempts to increase the effectiveness of BCNU therapy. The alkyltransferase activity in the liver, kidney, lung, and prostate of Copenhagen rats was 66, 37, 65, and 122 fmol/mg protein, respectively. The activity in the Dunning R3327G rat prostate tumor was found to be 129 and 126 fmol/mg protein from intact and castrated animals, respectively. The level of this protein remained low in the tissues and tumors of rats for up to 24 h and slowly began to rise at 36 h following an i.p. injection of 80 mg/kg O6-benzylguanine. Animal survival and body weight as well as tumor volumes were monitored in rats bearing prostate tumors in the flank area that had received no treatment, O6 benzylguanine alone, BCNU alone (5.5-60 mg/kg), or 80 mg/kg O6-benzylguanine 1 h prior to BCNU (5.5 mg/kg). When O6-benzylguanine was combined with BCNU therapy, there was a regression in tumor growth that was not observed in animals treated with an equal dose of BCNU alone. A similar regression in tumor growth was observed in animals treated with a higher dose of BCNU alone (45 mg/kg); however, this regimen was more toxic than O6-benzylguanine plus BCNU (5.5 mg/kg) as determined by animal weight loss. The mean weight loss observed in animals treated with BCNU alone and in those given the combination was 24% and 6%, respectively. Histopathology revealed that animals receiving either BCNU alone or the combination had a decrease in all types of bone marrow cells, a loss of intestinal crypts, and a decreased number of lymphocytes in the spleen. The enhancement of the antitumor effect on BCNU by pretreatment with O6-benzylguanine supports a role for this therapy in the treatment of prostate cancer. PMID- 8500229 TI - Vinorelbine high-affinity binding to human platelets and lymphocytes: distribution in human blood. AB - Using [3H]-vinorelbine, we demonstrated the presence of saturable and time dependent high-affinity binding sites on human platelets and lymphocytes. The dissociation constant and binding-site values observed were 200 +/- 38 nM, 20.0 +/- 2.2 amol/platelet, and 155 +/- 20 amol/lymphocyte, respectively. Among other blood components, saturable low-affinity binding of vinorelbine to alpha 1-acid glycoprotein, serum albumin, and lipoproteins was observed. The binding to erythocytes was nonsaturable. Given the relative concentrations of these carriers, vinorelbine mainly distributes in the platelet compartment in blood (> 70%), and the amount of free vinorelbine in plasma relative to the total amount in blood is < 2%. It is suggested that because of the preferential retention of vinorelbine by platelets, variations in the platelet count are very likely to produce changes in the free blood fraction of vinorelbine. PMID- 8500231 TI - The vasodilator-heart failure trials (V-HeFT). PMID- 8500230 TI - Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine. AB - Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5 Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6-7 days. Delayed high dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa. PMID- 8500232 TI - The Vasodilator-Heart Failure Trials (V-HeFT). Mechanistic data from the VA Cooperative Studies. Introduction. PMID- 8500233 TI - The influence of atrial fibrillation on prognosis in mild to moderate heart failure. The V-HeFT Studies. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Atrial fibrillation occurs commonly in heart failure; however, its importance in terms of prognosis is controversial. METHODS AND RESULTS: We assessed the relation of atrial fibrillation on first Holter monitor to morbidity and mortality in mild to moderate heart failure in 632 patients in the Veterans Affairs Vasodilator-Heart Failure Trial (V-HeFT) I and 795 patients in V-HeFT II: Ninety-nine patients in atrial fibrillation and 533 patients in sinus rhythm were followed for a mean of 2.5 years (range, 6 months to 5.7 years) in V-HeFT I; 107 patients in atrial fibrillation and 688 patients in sinus rhythm in V-HeFT II were followed for a mean of 2.5 years (range, 6 months to 5.0 years). V-HeFT I compared treatment with prazosin, hydralazine-isosorbide dinitrate, and placebo, whereas V-HeFT II compared hydralazine-isosorbide dinitrate with enalapril. Follow-up evaluations included serial Holter monitors, serial metabolic exercise testing, hospitalization data, and clinical examinations. In V-HeFT I, cumulative mortality at 2 years was 0.34 for patients with atrial fibrillation and 0.30 for patients in sinus rhythm (p = 0.25). Overall cumulative mortality was 0.54 for atrial fibrillation patients and 0.64 for sinus rhythm patients (p = 0.86). In V HeFT II, cumulative mortality at 2 years was 0.20 for patients with atrial fibrillation and 0.21 for patients with sinus rhythm (p = 0.68), and overall cumulative mortality was 0.46 for atrial fibrillation patients and 0.52 for those in sinus rhythm (p < 0.46). Sudden death was not increased with atrial fibrillation in V-HeFT I patients (p = 0.64) or in V-HeFT II (p = 0.68). By multivariate analysis, the relative mortality risk for atrial fibrillation was 0.95 in V-HeFT I and 0.76 in V-HeFT II: Metabolic exercise testing, showed no significant difference in mean change in peak oxygen consumption between patients with atrial fibrillation and those with sinus rhythm in V-HeFT I and a slight decrease late in V-HeFT II: Hospitalization rate for heart failure was not increased in either study. The embolic event rate was not increased for atrial fibrillation patients: 3% versus 4.9% of patients in sinus rhythm (p = 0.41) in V HeFT I and 4.0% versus 6.0% in V-HeFT II patients (p = 0.44). A secondary analysis compared mortality of patients in atrial fibrillation with that of patients in sinus rhythm on all Holters: Mortality was not increased overall (p = 0.72 in V-HeFT I and p = 0.35 in V-HeFT II). CONCLUSIONS: Atrial fibrillation does not increase major morbidity or mortality in mild to moderate heart failure. PMID- 8500234 TI - Influence of age on mechanisms and prognosis of heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Advanced age is commonly thought to carry a poor prognosis in congestive heart failure, but the case has not been established. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I and II) provided a large data base to assess the effect of age on hemodynamic profiles and survival in the failing heart. METHODS AND RESULTS: Patients were stratified into four categories according to age: < or = 55, 56-60, 61-65, and > 65 years. The distributions of treatments and baseline characteristics from history, physical findings, and laboratory data were analyzed for differences across age categories. Survival curves were calculated for age strata according to treatment, presence or absence of coronary artery disease, ejection fraction, and peak oxygen consumption. Risk ratios for age and treatment categories showed no consistent trend of treatment effect on mortality. Age was significantly associated with coronary artery disease, hypertension, rhythm disturbances, systolic blood pressure, ejection fraction, and peak oxygen uptake, but successive age strata did not show incremental changes. Survival curves did not show progressively steeper slopes with advancing age. In V-HeFT I, the oldest patients did have the poorest survival, but age interacted with the presence of coronary artery disease and randomization into the placebo group. CONCLUSIONS: Contrary to intuitive thinking, age alone did not shorten the survival in congestive heart failure patients who were < 75 years old and receiving optimal therapy. PMID- 8500235 TI - Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: In congestive heart failure patients, a single measurement of left ventricular ejection fraction (LVEF) provides important prognostic information. The importance, if any, of improvement or worsening in serial LVEF has not been defined. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT) data base was analyzed to determine the prognostic importance of LVEF changes. METHODS AND RESULTS: The data bases for V-HeFT I (n = 642) and V HeFT II (n = 804) were analyzed. All patients had heart failure with documented exercise intolerance and abnormal LVEF or cardiac dilatation by chest x-ray or echocardiography. Radionuclide LVEF was obtained at baseline, within 6 months, and at least yearly after randomization to treatment. Cumulative survival subsequent to LVEF follow-up measurements was calculated for strata defined by LVEF change from baseline. In V-HeFT I, patients treated with hydralazine/isosorbide dinitrate (H-I) experienced a significant (p < 0.001) increase in LVEF and a survival advantage over those treated with placebo and prazosin. In V-HeFT II, both treatment groups showed significant improvements in LVEF, with the increase with H-I greater than that with enalapril, and enalapril provided a significant survival advantage over H-I. Change (> 5) in LVEF from baseline at 6 months (V-HeFT I) and 1 year (V-HeFT II) were the strongest predictors of mortality among the serial measurements and were significant after adjustment for therapy and baseline LVEF. Baseline clinical variables were not helpful in predicting the patients who would experience an improvement in LVEF. CONCLUSIONS: In patients with heart failure, serial measurements of LVEF provide additional important prognostic information. Vasodilator therapy with H-I is associated with an improvement in LVEF and prognosis. Vasodilator therapy with enalapril improves LVEF less than H-I but provides an additional survival benefit. PMID- 8500236 TI - Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V HeFT VA Cooperative Studies Group. AB - BACKGROUND: The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure. METHODS AND RESULTS: Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death. CONCLUSION: Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical. PMID- 8500237 TI - Influence of prerandomization (baseline) variables on mortality and on the reduction of mortality by enalapril. Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V-HeFT II). V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diuretic therapy for chronic congestive heart failure (CHF) in the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V-HeFT II). METHODS AND RESULTS: Patients were randomly assigned to receive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active control treatment. Baseline variables were examined to determine their impact on risk of mortality and on relative response to treatment. Mortality rates were significantly higher in patients with severe ventricular arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impairment on a quality-of-life questionnaire, and high plasma norepinephrine or renin levels; and in patients in New York Heart Association (NYHA) classes III and IV. Coronary artery disease, duration of CHF, and patient age were not predictive of mortality. Enalapril reduced mortality significantly compared with hydralazine/isosorbide dinitrate in patient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril conferred significantly greater protection from mortality than hydralazine/isosorbide dinitrate in patients in NYHA classes I and II and in patients without arrhythmias or with < or = 10 premature ventricular contractions per hour. CONCLUSIONS: Of the prerandomization characteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia severity, and NYHA class identified subgroups of patients who benefited most from treatment with enalapril; a treatment interaction across strata was detected only for plasma norepinephrine and NYHA class. In no patient subgroup was the mortality with enalapril treatment significantly higher than the mortality with hydralazine/isosorbide dinitrate treatment. PMID- 8500238 TI - Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Congestive heart failure is a clinical syndrome characterized by neuroendocrine activation. Measurements of plasma norepinephrine and plasma renin activity were performed in the Vasodilator-Heart Failure Trial II (V-HeFT II) to characterize the effect of therapy on neuroendocrine activation and to examine the responses to therapy among patients with different degrees of activation. METHODS AND RESULTS: The baseline median plasma norepinephrine value (n = 743) was 490 pg/mL and the baseline median plasma renin activity (n = 737) was 6.9 ng.mL-1 x hr-1. Baseline plasma renin activity and plasma norepinephrine correlated poorly with each other (r = 0.12), implying that these two neuroendocrine systems are being activated by separate processes. By univariate analysis, the logarithms of the plasma norepinephrine (p < 0.0001) and the plasma renin activity (p = 0.01) were significantly related to all-cause mortality. In a multivariate analysis that included other significant univariate prognostic variables (i.e., baseline ejection fraction, peak oxygen consumption during exercise, and cardiothoracic ratio), log plasma norepinephrine but not plasma renin activity remained a significant (p = 0.02) predictor of mortality. Baseline plasma norepinephrine correlated poorly with baseline left ventricular ejection fraction (r = -0.18), peak oxygen consumption (r = -0.15), and cardiothoracic ratio (r = 0.11). Neither the plasma norepinephrine (r = 0.09) nor the plasma renin activity (r = 0.18) was closely associated with a quality of life assessment at baseline. The baseline plasma norepinephrine level in patients randomized to enalapril (mean, 593 +/- 388 [SD] pg/mL; n = 372) and to hydralazine and isosorbide dinitrate (mean, 544 +/- 297 pg/mL; n = 371) were similar. Thirteen weeks after randomization, plasma norepinephrine did not change (-5 +/- 393 pg/mL) in 312 patients randomized to enalapril but increased significantly by 74 +/- 311 pg/mL (p < 0.0001) in 300 patients assigned to hydralazine-isosorbide dinitrate. The plasma norepinephrine increased significantly more in patients assigned to hydralazine-isosorbide dinitrate than those on enalapril at both 13 weeks (p = 0.01) and at 1 year (p = 0.04) (90 +/- 302 pg/mL [n = 240] versus 14 +/- 376 pg/mL [n = 265]). Based on previous reports and examination of survival among several plasma norepinephrine strata, the baseline plasma norepinephrine data were grouped into three relatively homogeneous strata for further analysis. The cumulative mortality was significantly different between the three strata (p < 0.0001). The patients with plasma norepinephrine > 900 pg/mL had a higher mortality than those with corresponding values from 601 to 900 pg/mL or < 600 pg/mL. The survival benefit of enalapril compared with hydralazine-isosorbide dinitrate was most evident in those patients with a plasma norepinephrine value > 900 pg/mL. Although the plasma renin activity was not strongly associated with survival, patients in the upper quartile (> 16 ng.mL-1 x hr-1) had the worst prognosis. Among this group, the patients on enalapril demonstrated significantly better survival than those on hydralazine-isosorbide dinitrate (p = 0.02). CONCLUSIONS: This study confirms that plasma norepinephrine is an independent predictor of prognosis in patients with congestive heart failure. Hydralazine-isosorbide dinitrate treatment, unlike enalapril treatment, was associated with increased plasma norepinephrine concentration during the first year of follow-up. The enalapril group had a significantly lower mortality, and this survival benefit of enalapril as compared with hydralazine-isosorbide dinitrate was most evident among patients with the most marked neuroendocrine activation. Neuroendocrine activation is an important prognostic factor for patients with congestive heart failure and is an important determinant of the differential response to vasodilators. PMID- 8500239 TI - Enalapril decreases prevalence of ventricular tachycardia in patients with chronic congestive heart failure. The V-HeFT II VA Cooperative Studies Group. AB - BACKGROUND: Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death. METHODS AND RESULTS: Male patients aged 18 75 years with chronic heart failure were randomized to enalapril or hydralazine isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence. CONCLUSIONS: In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia. PMID- 8500240 TI - Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Recognition of the complex pathophysiology of heart failure and its high mortality has emphasized the need for prognostic markers that can be used in clinical assessment as well as in the design of mortality trials. Data from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V HeFT I, 642 patients; V-HeFT II, 804 patients) were therefore examined to determine the influence of prerandomization measurements on subsequent mortality. METHODS AND RESULTS: Patients entered into these trials were men with cardiac dysfunction and reduced peak exercise capacity. Measurements included in this analysis were left ventricular ejection fraction (EF) measured by radionuclide angiography, peak bicycle exercise oxygen consumption (VO2), cardiothoracic ratio (CTR) measured on a chest x-ray, ventricular arrhythmias assessed in a core laboratory by short-term Holter monitoring, plasma norepinephrine and plasma renin activity measured in a core laboratory only in V-HeFT II, and a variety of diagnostic and demographic data. The variables related only weakly to each other. EF, VO2, and CTR were powerful independent predictors of all-cause mortality in both studies. Ventricular arrhythmia was a significant independent predictor in V HeFT II but not in V-HeFT I. Plasma norepinephrine but not plasma renin activity measured in V-HeFT II also had independent prognostic value. Other variables did not exert an independent effect on mortality. CONCLUSIONS: Optimal assessment of the mortality risk in an individual or a group of individuals with heart failure uses measurement of EF, peak VO2, CTR, plasma norepinephrine, and the presence of ventricular arrhythmias. PMID- 8500241 TI - Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: To better define the effects of long-term vasodilator therapy on exercise performance in chronic congestive heart failure, we compared placebo with prazosin and with the combination of hydralazine and isosorbide dinitrate (Hyd-Iso) in 642 men over a 5-year period in V-HeFT I. METHODS AND RESULTS: Patients were randomized (double-blind) to 20 mg of prazosin daily or 300 mg of hydralazine plus 160 mg daily of isosorbide dinitrate or placebo. We compared enalapril (20 mg daily), a converting enzyme inhibitor, with Hyd-Iso in 804 men over another 5-year period in V-HeFT II: Background therapy in both trials consisted of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incremental work rates to a symptom-limited peak end point. Gas exchange anaerobic threshold (ATge) measurement was performed in the second trial. In V-HeFT I, an increase in peak VO2 with Hyd-Iso compared with placebo approached significance at 2 months (p < 0.16) and was significant (p < 0.04) at 1 year. In V-HeFT II, Hyd-Iso significantly increased peak VO2 compared with enalapril (p < 0.01 at 3 months, p < 0.02 at 6 months and 2 years). The changes in ATge measurements were not statistically different between the two treatment groups in V-HeFT II: CONCLUSIONS: Combination therapy with Hyd-Iso was more effective in increasing peak VO2 than placebo, prazosin, or enalapril in patients with mild-to-moderate congestive heart failure. Long-term data were confounded by mortality and other events, which may have led to an underestimate of the benefits of Hyd-Iso over placebo and an underestimate of the long-term benefits of enalapril on exercise performance. Therefore, short-term improvement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality. PMID- 8500242 TI - Echocardiographic variables as prognostic indicators and therapeutic monitors in chronic congestive heart failure. Veterans Affairs cooperative studies V-HeFT I and II. V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Echocardiographic indexes of ventricular function have become indispensable in clinical cardiology but have not been tested as prognostic markers or therapeutic monitors in clinical trials. In two Veterans Administration trials on heart failure (Vasodilator-Heart Failure Trials I and II, V-HeFT I and II), echocardiographic variables were analyzed as predictors and monitors and were compared with other indicators of cardiac performance. METHODS AND RESULTS: Echocardiograms were recorded before randomization and at follow-up intervals. Baseline measurements of left ventricular internal diameters (LVIDd, LVIDs), wall thickness (THd, THs), radius to thickness ratios (Rd/THd, Rs/THs), and mitral E-point septal separation (EPSS) were evaluated as predictors of mortality individually, in multivariate regression models with each other, and with nonechocardiographic predictors. Within-subject changes were compared between treatment groups. Cumulative survival curves were compared between strata formed by cut-points of EPSS and Rs/THs data. In Cox regression analyses, EPSS, LVIDs, and Rs/THs were significant predictors of mortality. In V-HeFT I, Rd/THd was a predictor in the presence of ejection fraction and peak oxygen uptake. In patients with EPSS > or = 21, there was an 83% increase in mortality in the subgroup of patients with Rs/THs > or = 2.5 compared with Rs/THs < 2.5 (p = 0.003), whereas there was no statistical difference for EPSS < 21. EPSS showed improvement in patients treated with hydralazine-isosorbide dinitrate compared with placebo at 2 and 18 months and a trend toward deterioration between 36 and 66 months. In V-HeFT II, there were no differences between enalapril and hydralazine-isosorbide dinitrate groups at follow-up. CONCLUSIONS: Echocardiographic variables, EPSS, LVIDs, and Rs/THs were shown to be predictors of mortality and monitors of treatment for heart failure in clinical trials. PMID- 8500243 TI - Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V HeFT VA Cooperative Studies Group. AB - BACKGROUND: Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. METHODS AND RESULTS: The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. CONCLUSIONS: Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators. PMID- 8500244 TI - Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. METHODS AND RESULTS: Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, his family, and/or hospital records. Hospitalization data also were obtained for patients who had died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission. In Vasodilator-Heart Failure Trial (V-HeFT) I, no significant difference in number of patients hospitalized or number of hospitalizations was noted among the treatment groups, although there was a trend for fewer and delayed cardiac hospitalizations in the hydralazine plus isosorbide dinitrate arm in which the survival was greater. In V-HeFT II, no difference in hospitalizations was apparent between the enalapril and hydralazine plus isosorbide dinitrate arms. Univariate predictors of hospitalization for all causes were reduced peak oxygen consumption (VO2) during exercise (p < 0.0001), reduced exercise duration (p < 0.0001), increased cardiothoracic ratio on chest radiograph (p < 0.0001), increased age (p < 0.03), and use of antiarrhythmic drugs (p < 0.013), whereas multivariate predictors were reduced peak VO2 (p < 0.0001), use of antiarrhythmic drugs (p < 0.015), and increased cardiothoracic ratio (p < 0.03). Univariate predictors of hospitalization for heart failure were peak VO2 (p < 0.0001), LVEF (p < 0.0001), reduced exercise duration (p < 0.0001), elevated cardiothoracic ratio (p < 0.0001), and elevated plasma norepinephrine (p < 0.0001). Multivariate predictors were exercise duration (p < 0.0001), LVEF (p < 0.04), elevated cardiothoracic ratio (p < 0.03), plasma norepinephrine (p < 0.0005), and coronary artery disease (p < 0.02). Time to first hospitalization, cause specific or overall, was considerably shorter for patients with baseline peak VO2 < 10 mL.kg-1 x min-1 compared with those with peak VO2 > 15 mL.kg-1 x min-1. CONCLUSIONS: Despite better survival in patients randomized to hydralazine plus isosorbide dinitrate compared with placebo and better survival in patients randomized to enalapril compared with hydralazine plus isosorbide dinitrate, no significant differences between the treatment groups were apparent in the incidence of hospitalization or time to first hospitalization for congestive heart failure, for cardiac reasons other than congestive heart failure, or for other causes. V-HeFT I and V-HeFT II data demonstrate no treatment effect on hospitalization, perhaps reflecting in part the effectiveness of the Veterans Affairs special heart failure clinics in dealing with worsening heart failure on an outpatient basis. Identification of predictors of hospitalization were similar in both studies. PMID- 8500245 TI - Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: Left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. We examined the relation between LV ejection fraction at rest, oxygen consumption at peak exercise (VO2), patient and physician assessments of clinical severity, and other clinical attributes in 804 patients with moderate heart failure. METHODS AND RESULTS: Ejection fraction correlated weakly with VO2, and mean ejection fraction was related to severity of symptoms. There was a statistical association between the patient's self-assessed quality of life questionnaire score and the physician-assigned New York Heart Association (NYHA) functional class; NYHA class was statistically associated with exercise performance. To identify other factors that might influence exercise capacity, comparisons of clinical attributes were made between patients grouped by VO2 within each stratum of LV function. Exercise performance was inversely related to plasma norepinephrine levels within the ejection fraction < 25% stratum. The percentage of patients reaching their anaerobic threshold was not different between groups, yet the peak heart rate increased with VO2 within all strata. Elevated venous pressure and cardiomegaly were inversely related to exercise performance. CONCLUSIONS: Clinical scales based on physician and patient assessment of symptoms were statistically associated with exercise capacity but do not accurately predict individual exercise performance. The strong association of heart rate response to exercise performance suggests that the variability of the chronotropic response to exercise contributes to differences in exercise capacity among patients with a similar degree of LV dysfunction. PMID- 8500246 TI - Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group. AB - BACKGROUND: The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial. METHODS AND RESULTS: The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II: Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL.kg-1 x min-1 in V-HeFT I and 13.7 mL.kg-1 x min-1 in V-HeFT II: Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p = 0.10 in V-HeFT I and p = 0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events. CONCLUSIONS: The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified. PMID- 8500247 TI - Spectral EEG parameters in patients with tick-borne encephalitis: a follow-up study. AB - Follow-up of spectral EEG parameters were reported for five patients with serologically verified tick-borne encephalitis. Comparisons were made for clinical data and findings of EEG analysis (power probability mapping, peak-power frequencies, and alpha/theta power ratios) were compared. A prominent feature of the EEG abnormality was the marked attenuation of background alpha activity. The peak-power frequency and absolute power analysis of three patients showed significant hemispheric asymmetry in the alpha and theta bands respectively. EEG topograms demonstrated persistent theta power fields in one patient. Alpha/theta power ratio was a reliable indicator for the recovery of rhythmic EEG activity during the convalescence. Reorganization of alpha activity appeared to lag behind the clinical improvement, its course was different from patient to patient. Because of the discrepancy of bioelectric and clinical findings the authors recommend long-term EEG monitoring in patients with tick-borne encephalitis. PMID- 8500248 TI - The effects of severe bruxism on sleep architecture: a preliminary report. AB - Analysis of sleep in 5 severe bruxists revealed consistent sleep abnormalities. These abnormalities consisted of decreased REM latency (90%), decreased percentage of REM sleep (85%), and increased number of sleep stage transitions (75%). This sleep pattern suggests that bruxing can have a deleterious effect on sleep in otherwise healthy individuals. This effect on sleep can in the long run lead to difficulty in daytime functioning similar to the effects of sleep apnea or nocturnal myoclonus. These data also reveal a significant first night effect, hence future attempts at replicating and expanding these findings should take that into consideration. The small number of subjects studied, the lack of a standardized assessment of their daytime functioning, the lack of information regarding the degree of teethware and daytime bruxing activity limit the generalizability of our findings. A controlled study with a larger sample size can help further delineate the nature of such sleep changes as well as their impact on the patient's overall functioning. PMID- 8500249 TI - Pain as a manifestation of seizure disorder. AB - Seizures can manifest in a variety of different clinical presentations. These include motor signs and symptoms, somatosensory and special sensory, psychic and autonomic signs and symptoms, and loss of impairment of consciousness. However, pain is a very uncommon clinical manifestation of a seizure. We describe a case where paroxysmal, acute-onset, right-sided arm-hand and facial pain was the initial and prominent manifestation of the seizure and was accompanied by interictal and ictal electrographic changes. PMID- 8500250 TI - Ictal midline epileptiform discharges. AB - Epileptiform discharges arising from the midline (Fz, Cz, Pz) are relatively uncommon. They have been found more frequently in children, are often activated by sleep, and correlate well with clinical seizures. Only a few studies discuss the issue of midline spikes, and all of them deal with interictal activity. We report 8 patients (age range 5 weeks to 17 years) in whom ictal midline discharges were recorded from scalp EEG. The following clinical seizures were recorded: complex partial, simple sensory and myoclonic. The ictal EEG showed spike and spike and slow wave complexes, rhythmic theta, background attenuation, and paroxysmal fast activity. Based on reports of animal experiments and on the variety of types of clinical seizures and their ictal EEG correlates in the patients reported here, it is suggested that the midline scalp EEG discharges do not represent the anatomical focus of origin of the seizures. They probably reflect secondary extension and summation of a remote source of epileptogenic activity. PMID- 8500251 TI - EEG monitoring during carotid surgery: who should do the monitoring? AB - EEG monitoring was carried out by an EEG technician during 100 consecutive carotid endarterectomies in a community hospital. The technician's rating of the EEGs correlated with an inhouse electroencephalographer's interpretation and with historical published data. We conclude that intraoperative EEG monitoring during carotid endarterectomies can adequately be carried out by a competent EEG technician provided adequate physician backup and supervision are available. PMID- 8500252 TI - The usefulness of one to two hour video EEG monitoring in patients with refractory seizures. AB - Video EEG monitoring for 1-2 hours was performed on 100 outpatients (57 females and 43 males) with refractory seizures or frequent paroxysmal events. Patients' ages ranged from 8 days to 67 years (mean age 21). At least one clinical seizure or paroxysmal event was observed in 66 patients; 24 of these patients had subtle seizures that would be difficult to observe without videotape monitoring. The combination of videotape and EEG monitoring was able to confirm the diagnosis in 80 cases. The referral diagnosis was changed in 37 patients; they included changes in seizure types in 17 epileptic patients; 10 patients were found to have pseudoseizures and 10 patients had nonepileptic neurological disorders. The yield of EEG seizure activity differed significantly between video EEG monitoring and routine EEG recording (p < 0.001). EEG seizure activity was reported in 77 patients with video EEG monitoring compared to 49 patients with routine EEG recording. We conclude that outpatient video EEG monitoring yields more information on the presence or absence of seizures and their types, improving patient management, and averting the need for prolonged inpatient intensive monitoring. PMID- 8500253 TI - Pure left hemianacousia: clinical and neurophysiological study. AB - Hemianacousia is a pure sensory deficit revealed by an abnormality of dichotic listening test associated with an asymmetry of late auditory evoked potentials. We report a case of a patient with pure left hemianacousia. LAEPs, MLAEPs and P300 were recorded. Left hemisphere N90 wave amplitude was significantly reduced over the right hemisphere. CT scan revealed a right temporal hematoma which seemed to correspond to area 41. PMID- 8500254 TI - Test of repeated operations and logistic regression as to the efficacy of brain mapping. AB - The object of this paper is to apply two new methods, those of repeated observations and logistic regression in order to verify the validity of qEEG. These methods are applied using children with hyperactivity and attentional disorders, according to DSM III-R. The results of sensitivity and specificity were similar. PMID- 8500255 TI - Sodium valproate: quantitative EEG and serum levels in volunteers and epileptics. AB - Twelve healthy adults and 12 epileptics had quantitative EEG tests while taking valproic acid. The results indicated that the total power of dominant frequency band and the frequency of dominant occipital rhythm were relatively stable in healthy awake adults. A single 400 mg oral dose of sodium valproate had similar influence on the total power of dominant frequency band in both healthy adults and epileptics. The total power of dominant frequency band tended to rise at 2 and 6 hours after medication in subjects with serum VPA concentrations reaching a peak after 2 hours. There was a tendency to rise at 4 and 8 hours in subjects with serum VPA concentrations which peaked after 4 hours. The curve of the total power with time had two peaks. A single oral dose of sodium valproate did not have a marked influence on the frequency of dominant rhythm in the occipital areas in healthy adults or in epileptics. PMID- 8500256 TI - Multipoint linkage analysis in X-linked juvenile retinoschisis. AB - Thirteen families with X-linked juvenile retinoschisis (XLRS) were studied in order to evaluate the linkage relationship between the XLRS locus (RS) and seven X-chromosomal DNA markers. Linkage was found between RS and DXS9 (theta max = 0.11, Zmax = 4.17), DXS16 (theta max = 0.06, Zmax = 7.72), DXS41 (theta max = 0.06, Zmax = 8.13) and DXS43 (theta max = 0.03, Zmax = 6.11). Recombinants were found between RS and all loci studied. Multipoint linkage analysis and recombination analysis significantly favour the order of Xpter-(DXS9, (DXS16 DXS43))-RS-DXS41-Xcen. PMID- 8500257 TI - Familial complex chromosomal rearrangement resulting in duplication/deletion of 6q14 to 6q16. AB - A familial complex chromosomal rearrangement (CCR) was ascertained through a mentally retarded, dysmorphic individual. Carriers of the CCR have the karyotype 46,XX or XY, t(6;15)(q16;q21), ins(3;6)(q12;q14q16), and malsegregation of the CCR resulted in loss of the segment 6q14 to 6q16 in the proband, and in an additional copy of the same segment in three members of the extended family. The proband has features similar to other reported cases with deletion of 6q1. The individuals with duplication of 6q14 to 6q16 have moderate mental retardation, short stature, obesity, microcephaly, brachycephaly, a short smooth philtrum, central hair whorl, simian creases, 5th finger brachydactyly and skeletal disproportion. In the 4-generation family, CCR carriers have a 20% empiric risk of phenotypically abnormal livebirths. PMID- 8500258 TI - Nager acrofacial dysostosis: minor familial manifestations supporting dominant inheritance. AB - We report on a girl with Nager acrofacial dysostosis, three of whose relatives had variable mild anomalies of the thumb. The possible relationship of such minor features to the radial limb anomalies in the proposita provides further evidence that the Nager syndrome can be the manifestation of a dominantly inherited disorder with very variable expressivity. PMID- 8500259 TI - Del(2q)--cause of the wrinkly skin syndrome? AB - We report the cases of a mother and her two sons with del(2) (q32). Their phenotypes are compared with those of 20 individuals reported previously in the literature. All described cases apparently have identical deletions. Common manifestations include small size at birth, retarded growth and development, cranio-facial dysmorphism and skeletal and ocular anomalies. Our patients also have symptoms of the wrinkly skin syndrome (WSS), which is characterized by the wrinkling of the abdominal skin and of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, musculoskeletal anomalies, microcephaly, mental retardation and an old appearance. Our three patients show a striking pattern in skin biopsies when viewed by light microscopy, and a peculiar grimacing was noted in the boys. Their serum copper and caeruloplasmin levels are slightly raised. PMID- 8500260 TI - Late-onset familial amyloid polyneuropathy with the TTR Met 30 mutation in France. AB - Four unrelated French cases of familial amyloid polyneuropathy are reported. Clinical onset ranged from the sixth to the ninth decade. Sensory signs were predominant initially in the lower limbs; motor changes, and in one case autonomic involvement, appeared later. Amyloid disease was clinically limited to the peripheral nervous system. In two cases, there was no evidence of familial disease. DNA analysis was performed in these four patients and in two children of Patient 1. Restriction analysis of amplification products of exon 2 of the transthyretin gene was positive for the valine 30 to methionine mutation. These four unrelated patients live in different areas of France. Further studies are needed to determine whether these mutations have a common origin and whether they are related to the Portuguese mutation. PMID- 8500261 TI - Normal immunological status in four patients with ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC-syndrome). AB - Lobster-claw deformity of the extremities, clefting of the primary and secondary palate, ectodermal dysplasia, and atresia of the lacrimal system are common features of the ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC syndrome). The patients often suffer from repeated infections of eyes, upper respiratory tract and urogenital system. To exclude an immunodeficiency as cause of the infectious predisposition in patients with EEC-syndrome, we screened the immunosystem in four related patients with EEC-syndrome. All patients were found to present normal immunoglobulin production, complement activity, lymphocyte-, and granulocyte function. We conclude that recurrent infections observed in the EEC-syndrome are not caused by an immunological defect, but seem to result solely from anatomical anomalies. PMID- 8500262 TI - Attitudes towards prenatal diagnosis and selective abortion among patients with retinitis pigmentosa or choroideremia as well as among their relatives. AB - Genetic counselling endeavours to be nondirective. However, the availability of prenatal diagnosis may direct clients towards accepting and using these methods. It is time to investigate the attitudes of clients in order to monitor the psychological and social effects of new genetic techniques. As prenatal diagnosis was possible for choroideremia (C), but not for retinitis pigmentosa (RP) in 1988 89, we used a questionnaire to compare the attitudes of C and RP patients, their relatives and C carriers to prenatal diagnosis. The response rate was low (35%) and no significant differences between RP and C groups came to light. However, C carriers accepted prenatal diagnosis and also selective abortion more easily, but, on the other hand, they showed more uncertainty than did the other groups. This indicates that the availability of prenatal diagnosis may confuse those concerned. In general, about 60% of all the respondents had a positive attitude to the prenatal diagnosis of RP or choroideremia, though only about 30% would use if for abortion. Over 80% of all the respondents wanted to know the opinion of the genetic counsellor. PMID- 8500263 TI - Exclusion map of the gene for neuraminidase from 10(pter-->p15.1) PMID- 8500264 TI - Eronen syndrome identical with DOOR syndrome? PMID- 8500265 TI - The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation. AB - In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection. PMID- 8500266 TI - Spontaneous recovery from the Guillain-Barre syndrome is associated with anti idiotypic antibodies recognizing a cross-reactive idiotype on anti-neuroblastoma cell line antibodies. AB - The presence of suppressive antibody activity in sera from patients spontaneously recovered from the Guillain-Barre syndrome was investigated by analyzing the ability of postrecovery serum to inhibit anti-neuroblastoma cell line antibody binding in sera from seven patients in the prerecovery phase or with a chronic form of the disease. All 12 recovered patients analyzed were found to have inhibitory IgG antibodies in their postrecovery sera, of which the F(ab')2 fragments mediated the inhibitory effect. The pattern of inhibition suggests that about half of the patients share cross-reactive idiotypes of high affinity. The efficiency of the inhibition mediated by anti-idiotypic antibodies in spontaneously recovered patients was twice as high as that mediated by anti idiotypes present in therapeutical preparations of polyclonal immunoglobulins for intravenous use (IVIG). Affinity chromatography of IVIG and serum from a recovered Guillain-Barre syndrome patient on autoantibody-containing F(ab')2 fragments revealed, first, that inhibitory anti-idiotypic antibodies are specifically retained on autoantibodies and, second, that these antibodies constitute less than 1% of the total IgG antibody content. PMID- 8500267 TI - In vitro tumor necrosis factor production by mononuclear cells from lepromatous leprosy patients and from patients with erythema nodosum leprosum. AB - The production of tumor necrosis factor (TNF) by Mycobacterium leprae-stimulated phagocyte cells, isolated from lepromatous leprosy patients (LL) and normal individuals, was evaluated, using the highly TNF-sensitive mouse fibrosarcoma cell line WEHI164cl13. Mononuclear cells, isolated from all individuals studied, showed a low level of spontaneous TNF production, except for patients undergoing erythema nodosum leprosum (ENL), in which we found significantly higher levels of TNF. Addition of M. leprae to the phagocyte cell culture enhanced TNF production in all groups studied, except in the group with untreated leprosy patients. Strongest M. leprae-induced TNF release was found in mononuclear cell cultures derived from ENL patients. Patients in the postreactional state showed significantly higher TNF levels than healthy controls. These findings support the idea that TNF plays a key role in the complex symptomatology of ENL. PMID- 8500268 TI - The relationship between serum titers of autoantibodies to C1q and age in the general population and in patients with systemic lupus erythematosus. AB - The aim of the present study was to assess the relationship between age and titers of autoantibodies to C1q (C1qAb) in individuals randomly selected out of the general population and in systemic lupus erythematosus (SLE) patients. Serum samples of 659 randomly selected individuals and 169 SLE patients were divided into 6 age groups from 20 to 79 years. IgG and IgA C1qAb titers were measured by ELISA. The highest titers of IgG and IgA C1qAb in sera of randomly selected individuals were found in the oldest age groups. In serum of SLE patients the highest titers of IgG C1qAb were found in the youngest age groups, whereas IgA C1qAb titers did not change with aging. It is concluded that the distribution pattern of IgG and IgA C1qAb titers in serum of individuals randomly selected out of the general population is similar to that of other autoantibodies. The increased titers of IgG C1qAb in serum of young patients with SLE suggest a role of these antibodies in the pathogenesis of the disease. PMID- 8500269 TI - GM3 as a target of anti-lymphocytic ganglioside antibodies in AIDS patients. AB - IgG antibodies reacting with the GM3-comigrating band extracted from pooled AIDS lymphocytes were detected in 33.3% of AIDS patients sera, in 8% of asymptomatic anti-HIV-positive subjects, in none of the sera obtained from asymptomatic anti HIV-negative drug abusers, from patients with acute B and chronic C hepatitis, and from healthy donors. All positive sera reacted selectively with the GM3 comigrating band obtained from AIDS lymphocytes but not with the corresponding band from normal lymphocytes. The lymphocytic ganglioside autoantigen was revealed as GM3. In addition, two main data were shown: (a) AIDS lymphocytes have an increased concentration of GM3 and (b) the ceramide of AIDS lymphocytic GM3 has a different percentual composition of fatty acids in contrast to control cells. It is suggested that these quantitative and qualitative changes might be responsible for the appearance of circulating anti-lymphocytic GM3 antibodies. PMID- 8500270 TI - In vivo and in vitro suppression of T-cell receptor alpha/beta CD4- CD8- T lymphocytes by cyclosporine A. AB - We treated a patient with a combined immunodeficiency and disease pathology resembling GvHD with cyclosporine. This disorder was characterized by exfoliative dermatitis, lymphadenopathy, and lymphocytosis of a novel T-cell phenotype (CD3+ TCR alpha/beta+ CD4- CD8-). The patient's peripheral blood T cells had elevated cytolytic activity and expressed increased levels of IL2R, HLA-DR, and CD45RO. Treatment with CsA resulted in marked clinical improvement, resolution of the lymphocytosis, and reduced cytolytic activity of peripheral blood T cells. T-cell HLA-DR and IL2R expression was reduced by cyclosporine, but CD45RO remained intact on virtually all circulating T cells. CsA also inhibited the cytolytic activity and cytokine production of in vitro cultured TCR alpha/beta+ CD4- CD8- cell lines. Our data suggest that alleviation of the patient's clinical symptoms resulted from cyclosporine-mediated suppression of proliferation, cytotoxicity, and inflammatory cytokine production of TCR alpha/beta+ CD4- CD8- T lymphocytes in vivo. The response of this patient to cyclosporine, which was similar to that seen in true GvHD, provides further evidence that these conditions share common pathogenetic pathways. PMID- 8500271 TI - Characterization of the progression signal for human T-cell proliferation provided by monoclonal antibodies to the CD3-TCR complex. AB - Following T-cell activation, two distinct stages in the proliferative response can be identified. The first stage or state of competence (G0 to G1 transition) is defined by the acquisition of the ability of activated T cells to proliferate in response to growth factors. The second or progression phase relates to the progression of cells to DNA synthesis in response to exogenous growth factors (e.g., IL-2) or inducers of growth factor synthesis (e.g., phorbol esters). In the present manuscript we provide evidence that soluble monoclonal antibodies (mAbs) to CD3 or the T-cell receptor (TCR), similar to the phorbol esters, can induce IL-2 production and cell proliferation in competent but not resting T cells. The data indicate the role of CD3-TCR complex triggering not only as an "activating or competence signal" but demonstrate its capacity to signal in the progression phase as well. However, there were distinct differences when competent T cells were stimulated by phorbol ester compared to soluble antibodies to CD3 or TCR. Antibodies to the CD3-TCR complex, when compared to phorbol ester, induced less proliferation in competent, memory T cells (CD45RO) than in competent, naive T cells (CD45RA). In contrast to phorbol ester, the induction of IL-2 transcription and cell proliferation in competent cells by soluble mAbs BMA 031 (anti-alpha/beta T-cell receptor) or OKT3 (anti-CD3) was inhibited by cyclosporin A (CsA). This implies that in activated T cells there is a step between activation of the CD3-TCR complex and the point(s) of action of phorbol ester that is susceptible to CsA in activated cells. Alternatively, the data may indicate involvement of different regulatory elements with different sensitivities to CsA for the induction of IL-2 transcription by phorbol ester or antibodies to the CD3-TCR complex. PMID- 8500272 TI - Cloning of a human IgM autoantibody bearing a cross-reactive idiotype in a lambda expression vector: a new approach to studying autoantibodies. AB - The monoclonal antibody 4B4 is a human IgM,kappa which expresses a cross-reactive lupus-associated idiotype and has anti-Sm binding activity. We find that the VL nucleotide sequence of 4B4, like the 4B4 VH region, is encoded by unmutated germline genes. The 4B4 VH and VL were cloned into the ImmunoZap lambda expression vector to produce three recombinant immunoglobulin polypeptides. These recombinant polypeptides expressed, respectively, either the 4B4 VH or VL alone or a VH/VL heterodimer. ELISA showed that the VH/VL heterodimer retained anti-Sm antibody activity. The 4B4 idiotype was found predominantly on the VH. This report describes: (i) a method for producing recombinant immunoglobulin molecules from an IgM-secreting B cell line and (ii) the ability of recombinant antibody fragments expressed in Escherichia coli to retain the structural and antigenic properties of the native molecule. PMID- 8500273 TI - A major portion of polymorphonuclear leukocyte and T lymphocyte migration to arthritic joints in the rat is via LFA-1/MAC-1-independent mechanisms. AB - The importance of the leukocyte CD11/CD18 beta 2 integrins for leukocyte adhesion and for leukocyte migration to inflamed tissues is well recognized. However, the role of CD11/CD18 molecules and their subtypes, such as LFA-1 and MAC-1, in leukocyte migration to arthritis is not known. Here we report the effects of a new monoclonal antibody (mAb) TA-3, which recognizes and blocks rat LFA-1 (CD11a/CD18), on the migration of 51Cr-labeled rat blood polymorphonuclear leukocytes (PMNL) and 111In-labeled spleen T lymphocytes into the inflamed joints of rats with adjuvant arthritis and to dermal inflammation. The mAb MRC OX-42, which reacts with and blocks rat MAC-1 (CD11b/CD18), was also evaluated. In established arthritis, iv anti-LFA-1 (TA-3) inhibited, up to 50% (P < 0.006) of PMNL accumulation in the talar and metatarsal joints but had no effect on T lymphocyte migration to the joints. In the same animals, anti-LFA-1 partially (35 50%) inhibited PMNL accumulation in acute dermal inflammation induced by zymosan activated serum (ZAS, C5ades Arg), IL-1 or endotoxin (P < 0.01) and suppressed T lymphocyte migration to dermal DTH, IFN-gamma, LPS, and poly-I:C-induced inflammation by 60-80%. Anti-MAC-1 (OX-42) by itself had no effect on PMNL migration. Anti-MAC-1 combined with anti-LFA-1 did not inhibit PMNL or T lymphocyte migration to joints any more than anti-LFA-1 alone. However, the addition of anti-MAC-1 to anti-LFA-1 further inhibited PMNL migration to acute dermal inflammation by up to 90%. These findings demonstrate that LFA-1 on PMNL plays a major role in PMNL migration but not in T cell migration to arthritic joints. MAC-1 on PMNL appears less important. Furthermore, while LFA-1 and MAC-1 on PMNL and LFA-1 on T lymphocytes mediate much of the migration to dermal inflammation, the migration of these cells to arthritis has a major LFA-1/MAC-1 independent component. PMID- 8500274 TI - Monoclonal antibodies to heparan sulfate inhibit the formation of thrombin antithrombin III complexes. AB - As components of the cell surface and extracellular matrix, heparan sulfate proteoglycans play an important role in the function of most organs, including the vasculature. Autoimmunity to heparan sulfate (HS) glycosaminoglycan epitopes may play a role in tissue injury. Tight skin (TSK) mice suffer a disease resembling scleroderma, an autoimmune disease associated with alterations in the extracellular matrix of the skin and other organs, as well as vascular injury. Studies of autoimmunity to HS were performed in TSK mice employing a solid-phase radioimmunoassay for the detection of anti-HS antibody. An increase in the clonal frequency of hybridomas secreting anti-HS antibody was noted in TSK mice compared to that in control mice. Liquid-phase competitive inhibition specificity studies of IgM and IgG anti-HS monoclonal antibodies demonstrated little cross-reactivity with other glycosaminoglycans. Some cross-reactivity, albeit at lower affinity, with phosphorylated antigens including DNA, cardiolipin, and RNA polymerase were noted. Negatively charged sulfate groups and carboxyl groups played a role in the immunodominant site. Monoclonal antibodies to HS inhibited the binding of HS to antithrombin III and the formation of thrombin-antithrombin III complexes. These results demonstrate autoimmunity to HS in TSK mice. The results also indicate that HS is a high-affinity antigen of pathological significance for anti-DNA and anti-phospholipid antibodies. Thrombosis induced by polyclonal anti-phospholipid antibodies may be mediated by a subset of these antibodies with high affinity for HS. Anti-HS antibodies may promote a procoagulant state by the blockade of HS binding to antithrombin III, inhibiting the accelerated formation of thrombin antithrombin III complexes. PMID- 8500275 TI - Neopterin levels in plasma during a longitudinal study in an area endemic for malaria. AB - Neopterin levels in plasma were measured during a longitudinal study of 75 patients living in an area endemic for malaria. The maximum levels were observed in August/September, the period of peak transmission of the disease. During the dry season, levels remain elevated. No relationship was found between the level of neopterin and the individual's immune status against malaria. Tumor necrosis factor (TNF), activated T lymphocytes subpopulations, soluble interleukin 2 receptors, and anti-circumsporozoite protein antibodies were not correlated with neopterin levels during the period of peak transmission. In contrast, neopterin levels were correlated with anti-Plasmodium falciparum antibodies detected by immunofluorescence. It was concluded that, in a population of chronic parasite carriers subjected to repeated infestations, neopterin was a good indicator of slowly acquired immunity in stable transmission area, but it poorly reflected acute immune responses. PMID- 8500276 TI - Leukocyte adhesion deficiency syndrome: insights into the molecular basis of leukocyte emigration. AB - Important insights into the molecular basis of leukocyte emigration have come from studies of the leukocyte adhesion deficiency (LAD) syndrome, a rare heritable disorder caused by deficiency of the leukocyte beta 2 integrin receptor CD11/CD18. Severely affected patients exhibit a profound defect in neutrophil emigration to tissue. In vitro and in vivo studies demonstrate that the CD11/CD18 complex is the major determinant of the firm adhesion and transendothelial migration of neutrophils. The inability of CD11/CD18-deficient neutrophils to adhere to and migrate across endothelium results in a profound defect in neutrophil emigration to tissue which leads to recurrent infection. The careful investigation of the LAD syndrome has also helped to characterize CD11/CD18 independent adhesion pathways such as the selectin receptors and the beta 1 integrin receptor VLA-4. Interestingly, although the LAD syndrome clearly establishes the importance of the beta 2 integrin receptors in host defense, inhibition of CD11/CD18 function may represent a novel approach to the therapy of inflammatory and immune disorders. PMID- 8500277 TI - Chronic granulomatous disease: the solving of a clinical riddle at the molecular level. AB - Chronic granulomatous disease is an uncommon inherited disorder of phagocytes in which the defective production of microbicidal oxidants leads to an enhanced susceptibility to bacterial and fungal infections. Despite the near uniform absence of the respiratory burst in CGD phagocytes, there is a striking clinical and genetic heterogeneity in this disorder. The recent elucidation of the molecular basis of CGD now provides an explanation for this heterogeneity. CGD is caused by a defect in any one of four components of NADPH oxidase, the enzyme responsible for the generation of the antimicrobial oxidants. X-linked inheritance is seen in approximately 65% of patients and results from mutations in the gene encoding the gp91-phox subunit of the cytochrome b558 component of the oxidase. The remaining 35% of patients inherit CGD in an autosomal recessive manner due to mutations in the genes encoding the remaining three oxidase components: p22-phox (chromosome 16), p47-phox (chromosome 7), and p67-phox (chromosome 1). Deletions, insertions, and point mutation leading to premature stop codons, amino acid substitutions, and splice site defects have all been identified. Most CGD patients have mutations unique to their families. The diversity of these mutations and the multiple genes affected provide an explanation for the clinical and genetic heterogeneity of CGD. PMID- 8500278 TI - Lymphokine regulation and the role of abnormal regulation in immunodeficiency. AB - T cell-derived lymphokines mediate or modulate various aspects of the immune response and immunodeficiency states related to abnormalities in lymphokine production or regulation are now being recognized. One example of this is seen in the fetus and neonate, in whom a physiologic immunodeficiency appears to reflect in part deficient production of certain lymphokines, including interferon-gamma, IL-4, and IL-5. The deficiency in production of these lymphokines appears to reflect to a large extent the paucity of memory T cells during these periods of life. Diminished lymphokine production has also recently been implicated as the cause for three cases of primary severe combined immunodeficiency. In disorders associated with excess IgE production, including allergy, hyper IgE syndrome, and Omenn's syndrome, excess IL-4 production relative to the production of interferon gamma may play a contributory role. Regulation of the production of these and other T cell-derived lymphokines appears to be affected predominantly by control of lymphokine gene transcription, the basis for which is just now becoming understood at a molecular level. The elucidation of these regulatory mechanisms offers the promise for understanding the basis for disordered lymphokine production in immunodeficiency states. PMID- 8500279 TI - Regulation of antibody responses: the role of complement and adhesion molecules. AB - To analyze the importance of cell surface-associated molecules in modulating the immune response by facilitating T/B cell interaction, we used the T cell dependent antigen, bacteriophage phi X174. Taking advantage of "experiments of nature", we studied specific antibody synthesis in patients with deficiencies of complement components or of the adhesion molecule CD11/CD18 (leukocyte adhesion defect, LAD) and guinea pigs and dogs with early complement component deficiency. Following intravenous injection of bacteriophage phi X174 into normal subjects or animals, a primary response consisting of IgM, a secondary response consisting of IgM and IgG, and a tertiary, predominantly IgG response can be distinguished. Patients and guinea pigs deficient of early complement component and LAD patients responded to repeated phage immunization with depressed antibody titers, lack of or inadequate amplification, and failure to switch from IgM to IgG, suggesting a defect in generating antigen-specific memory cells. Several mechanisms have to be considered: (i) The complement portion of the antigen-antibody complement complex facilitates the accumulation and trapping of antigen in lymphoid organs, thus improving the response to Ag at low concentrations. (ii) Immune complexes preferentially bind to antigen-specific B cells, cells expressing Fc receptors, or CR2 and CR3, the receptors for C3bi. (iii) The weak binding established between the MHC-II/Ag complex and the TCR complex is strengthened through the binding of several adhesion molecule pairs. (iv) Receptor-ligand binding initiates activation signals. The concept of binding/signaling via interacting molecules is further supported by the observation that mAb 60.3, recognizing the beta chain of CD11/CD18, blocks in vitro synthesis of antibody to bacteriophage by primed PBMC. PMID- 8500280 TI - Putative mechanisms of the effect of intravenous gamma-globulin. PMID- 8500281 TI - In vivo dissection of lymphocyte signaling pathways. AB - Attempts to dissect signaling pathways leading from the T cell antigen receptor to the cell interior rely primarily on careful biochemical analysis of changes in cellular metabolism provoked by ligand. An alternative approach tests hypotheses regarding the mechanism of T cell activation by altering the representation of putative signaling molecules in otherwise normal lymphocytes using gene manipulation techniques. Rigorous implementation of this strategy has defined crucial roles for two protein tyrosine kinases, p56lck and p59fyn, in T cell signaling pathways. Working from this strong foundation, a molecular description of the T cell activation sequence may now be achievable. PMID- 8500282 TI - The role of the major histocompatibility complex in autoimmunity. AB - In the case of many autoimmune diseases, HLA genes are the genes most closely associated with disease susceptibility. Recent major advances in the ability to determine particular HLA genotypes in individuals now allow us to identify the precise alleles most closely associated with disease. Rheumatoid arthritis, long known to be associated with HLA-DR4, provides a good model for review of this progress, demonstrating how methodologic advances have led to an improved understanding of the immunogenetic basis of this disease, with implications for both pathogenesis and potential therapeutic interventions. PMID- 8500283 TI - The rheumatic diseases of children: reflections on the past, present, and future. PMID- 8500284 TI - The politics of closing state mental hospitals: a case of increasing policy gridlock. AB - There are political and administrative barriers to closure of the remaining state mental hospitals. Some of these barriers owe their existence to the current lack of community-based alternatives for the care and treatment of the severely mentally ill. In addition, uncertainty of the future funding and regulatory commitment of state governments to community programs contributes to an unwillingness by influential groups to recommend or implement closure. Finally, other barriers include rigid budgetary processes, the self-interest of public employees, and the lack of consensus in the decision making process. The result is that even when the case for closure of a state mental hospital is convincing, these political and administrative factors can cause "policy gridlock." This article describes how such policy gridlock occurs and offers several suggestions as to how it can be prevented. PMID- 8500285 TI - Assessing levels of adaptive functioning: the Role Functioning Scale. AB - This paper reports data on reliability and validity of the Role Functioning Scale (RFS) a measure of level of functioning of adults in four domains. Psychometric properties were tested on an inner city sample of 112 psychiatrically disturbed and well, predominantly African-American, low-income mothers of young children. The RFS has good interitem, test-retest, and interrater reliability. The four scales and global RFS Index discriminated accurately between well and disturbed subjects. The Global RFS Index was significantly correlated with self-esteem and degree of disturbance. Individual scales demonstrated predicted relationships with quality of child-rearing and other independent behavioral indices. Results are discussed in terms of the unique information provided by the RFS and its potential contribution to treatment planning. PMID- 8500286 TI - Potential risk factors for rape in three ethnic groups. AB - This article describes the frequency of possible risk factors that emerged during a cross-cultural study of psychosocial response to sexual assault among African American, Hispanic, and non-Hispanic white women presenting for treatment at a major urban rape treatment center. Of 881 victims screened, 51% had no observable risk factors while 49% fell into categories of variables that previous research has associated with increased vulnerability. Included were mental disability (psychiatric or developmental), a prior history of rape or incest, tourist or visitor status (site unfamiliarity), and homelessness. Ethnic groups differed significantly in these categories, suggesting socioeconomic and cultural variables that may affect rape statistics and that should be taken into account in rape prevention programs in the community. PMID- 8500287 TI - Perceived costs and benefits of membership in a self-help group: comparisons of members and nonmembers of the Alliance for the Mentally Ill. AB - We assess the utility of looking at the costs/barriers and benefits/incentives of belonging to an Alliance for the Mentally Ill (AMI) self-help group. Support for bimotivational factors of costs and benefits was found. Comparisons were made between members vs. nonmembers and between more active vs. less active members. Implications for theory and application are discussed. PMID- 8500288 TI - Developing a systems approach to caring for persons with borderline personality disorder. AB - Most community mental health centers have not established a treatment approach for seriously ill persons with borderline personality disorder that is multi focused, coordinated, comprehensive, and continuous. The authors propose that the systems approach to caring for persons with schizophrenia (Stein, Diamond, & Factor, 1990) be modified and tested for its efficacy in helping seriously ill persons with borderline personality disorder. The rationale for proposing this model of care and its underlying principles and clinical components is described in this paper. PMID- 8500289 TI - Detection of substance use disorders in severely mentally ill patients. AB - Severe mental illness is frequently complicated by substance use disorder. Approximately half of the severely mentally ill patients treated in acute care psychiatric settings have abused one or more of these substances. Despite the high rate of comorbidity, substance use disorders are generally not detected in acute care psychiatric settings, leading to incorrect diagnoses and ineffective treatments. The reasons for nondetection are complex, and research is needed to refine instruments and procedures for the detection of substance abuse in the severely mentally ill population. Nevertheless, clinicians can make better use of existing techniques of multimodal assessment to increase significantly the rate of accurate detection. PMID- 8500290 TI - The status of community mental health centers ten years into Block Grant Financing. AB - This study tracks the 761 community mental health centers which received federal grants as of 1981 and assesses their status 10 years after the shift to Block Grant financing. Contrary to what had been predicted (Biegel, 1982), the vast majority of centers remained open (88.3%), a small proportion were involved in mergers (8.5%) and an even smaller percentage closed (3.3%). No pattern was evident as to which centers closed or merged by type of initial funding, although some states showed a concentration of mergers and closures. Data from the 1988 Inventory of Mental Health Organizations are used to characterize the centers still in operation by facility type, ownership, service mix and revenue mix. In 1988, federally funded CMHCs accounted for 34% of the total patient episodes treated and 22.7% of the total revenues reported by specialty mental health providers in the United States. PMID- 8500291 TI - [Treatment of patients with acute myocardial infarct using angiotensin convertase inhibitors]. PMID- 8500293 TI - [Information resources in medicine]. PMID- 8500292 TI - [Klement Weber--4 March 1890, Domazlice--5 May 1971, Prague]. PMID- 8500294 TI - [Ischemic disease of the lower extremities]. PMID- 8500296 TI - On foods and vessels. PMID- 8500295 TI - [The decision-making process in indications for monitoring in patients with cardiac arrhythmia]. PMID- 8500297 TI - Effects of short-term oral digoxin on left ventricular diastolic filling in patients with ventricular dysfunction. An echo-Doppler study. AB - 34 patients with ventricular dysfunction (18 in NYHA class II and 16 in NYHA class III heart failure) whose clinical status was stabilized by diuretics and systemic vasodilators, entered a randomized trial to compare the effects of short term oral digoxin and active placebo on left ventricular diastolic function, non invasively evaluated by echo-Doppler transmitral left ventricular filling flow. At baseline patients were subdivided by reversal--the ratio of peak early (E) and late (A) transmitral filling velocities--E/A < 1 (group I) or normal--E/A > or = 1 (group II) echo-Doppler E/A ratio; group II exhibited a shorter deceleration time (125 +/- 20 ms vs 198 +/- 38 ms, p > 0.05) and isovolumic relaxation time (64 +/- 15 ms vs 93 +/- 10 ms; p < 0.05) as well as a higher peak E velocity (85 +/- 28 cm/s vs 54 +/- 20 cm/s; p < 0.05), ("restrictive" left ventricular filling pattern). After 4 weeks, no changes in all echo-Doppler parameters were noted in group I in response to either oral digoxin or active placebo. Clinical amelioration (defined as reduction by at least one functional class) was observed in 3 patients after digoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500298 TI - The prevalence of insulin resistance in essential hypertension. AB - The prevalence of insulin resistance and/or glucose intolerance (IR/GI) was evaluated in 98 patients with essential hypertension of various stages: a) Almost 35% of them had an abnormal or diabetic glucose tolerance test and 47% of the total number suffered from either/both IR/GI. b) The prevalence was high from stage I essential hypertension, which pointed to an early development of IR/GI, and no further increase during the development of hypertension was found if no antihypertensive drugs influencing IR/GI were taken by the patients. c) Obesity doubled the prevalence of IR/GI. d) No changes in total and HDL cholesterol or triglycerides were found in patients with IR/GI or stage-dependent. e) The presented criteria could be used for the diagnosis of IR/GI in clinical practice. PMID- 8500299 TI - [Early results and complications of percutaneous transluminal coronary angioplasty]. AB - The authors summarize the early results of coronary angioplasty in 234 patients, with special emphasis on complications. The follow-up group included 182 men (77.8%) and 52 women (22.2%) with a mean age of 52 (34-74) years. Single-artery involvement prevailed (216 patients, 92.3%); multiple artery involvement was diagnosed in 18 patients (7.7%). Overall, dilatation was performed in 273 stenoses; of this number, 213 procedures were successful (78.0%). The primary success rate in the whole group was 76.9% (180/234). The highest success rates were attained in concentric stenoses (88.8%), the lowest ones in complete occlusions (53.8%). Complications were present in 36 patients (15.3%), of this number 14 patients (5.9%) developed acute arterial occlusion; the complications were less severe in 22 patients (9.4%). Of the 14 patients with acute occlusion, eight (3.5%) developed severe complications. One female patient (0.43%) died, one (0.43%) had emergency surgery, and six (2.6%) developed uncomplicated acute myocardial infarction. Perfusion was restored by multiple dilatation in four patients; arterial occlusion, with good collateral circulation, did not result in myocardial infarction in two. Other complications were less severe and had no sequelae including, most often, arterial spasm (3.4%), large dissection demonstrated by angiography (2.6%), protracted hypotension (0.8%), and ventricular fibrillation in one case (0.43%). The article also considers the factors raising the risk of severe complications of coronary angioplasty, and the potential for their prevention and treatment. Coronary angioplasty, employed in an increasing number of patients with symptomatic stenosing atherosclerosis of the coronary arteries, is an effective method successful in 85-95% of patients. The complication rate, while low, is not absolutely negligible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500300 TI - [Cardiac hypertrophy in hypertension--clinical significance and possibilities of control]. AB - Left ventricular hypertrophy constitutes an essential risk factor for sudden death, myocardial infarction and heart failure. The death rates of patients with ECG-demonstrated cardiac hypertrophy are 4.8 times as high as those of healthy subjects. Cardiac hypertrophy is associated with a substantially increased incidence of ventricular arrhythmias. The condition is treatable in most patients. While the most effective group of drugs for controlling cardiac hypertrophy are ACE inhibitors; methyldopa, calcium antagonists, and beta blockers have also proved useful in the management of cardiac hypertrophy in hypertension. Diuretics other than indapamide are not appropriate for treating cardiac hypertrophy. An additional benefit of ACE inhibitor administration is they can favourable affect increased levels of collagen in the hypertrophic myocardium. The prognosis of hypertensive patients, whose treatment has lead to regression in cardiac hypertrophy in hypertension, is markedly better than that of patients in whom regression fails to be achieved. A role in the development of cardiac hypertrophy in hypertension, in addition to the blood pressure level, is played by a number of mechanisms; it is the genetic factor which has received most attention recently. As the prognosis of hypertrophic patients has been found to correlate more closely with left ventricular weight, determined by echocardiography, than with blood pressure, echocardiography should be employed more often in the future to help optimize antihypertensive therapy. PMID- 8500301 TI - A computer program for designing clinical trials with arbitrary survival curves and group sequential testing. AB - We present a program, mhghseq, for designing a clinical trial to compare two treatments. For a user-specified hypothesis and a user-specified alternative, mhghseq finds the number of subjects required to achieve a given size and power. It permits each treatment to have an arbitrary survival curve and it allows for group sequential testing. It provides solutions for small samples as well as for large samples. There may be a follow-up period after accrual is completed. Tests may be one or two-sided, either the log-rank or the Gehan test may be used, and either of two commonly used boundary forms--the O'Brien-Fleming or Pocock boundary forms--may be specified. Although mhghseq relies primarily on simulation to produce results, the large sample sequential boundary for the log-rank test optionally may be computed with an algorithm given here that is different from ones used in the past for this purpose. PMID- 8500302 TI - Design, methods, and conduct of the Optic Neuritis Treatment Trial. AB - The Optic Neuritis Treatment Trial (ONTT) was an investigator-initiated, multi centered, randomized, controlled clinical trial supported by cooperative agreements and grants. It was designed to evaluate the efficacy and safety of oral prednisone or intravenous methylprednisolone followed by oral prednisone as compared with oral placebo. The primary outcome measures were contrast sensitivity and visual field; secondary measures were visual acuity and color vision. Four hundred fifty-seven patients were followed for a minimum of 6 months and a maximum of 3 years. This article describes the design and the methods used to implement the ONTT. PMID- 8500303 TI - Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT). AB - The Visual Field Reading Center (VFRC) was established to assess visual field testing in the Optic Neuritis Treatment Trial (ONTT), to train and certify ONTT technicians, and to monitor the quality of the visual fields through evaluation of the technical aspects of the visual field testing. We describe the functions of the VFRC personnel and the standardized test protocols developed by the VFRC for Humphrey and Goldmann perimetry. We also describe the VFRC procedures for training and certifying visual field technicians, double-checking the eligibility of ONTT patients, assessing the quality of the visual field data, and processing visual field data. In addition, we describe the principles applied by the director and associate director of the VFRC in their clinical classification of the various localized and diffuse visual field defects observed in the Humphrey and Goldmann visual fields. The VFRC has processed more than 14,000 Humphrey and Goldmann visual field tests. The visual field quality control procedures and visual field defect classification process have been shown to be quite reproducible. Through quality control assessment procedures, we have been able to pinpoint a variety of problems at an early stage and promptly implement corrective measures. The standardized test protocols, technician training and certification procedures, and quality control assessment techniques used by the VFRC for the ONTT may serve as a model for future clinical trials employing visual field data as an outcome measure. These procedures can also be used to enhance visual field reliability in ophthalmological practices. PMID- 8500304 TI - Interim analysis in the pharmaceutical industry. PMA Biostatistics and Medical Ad Hoc Committee on Interim Analysis. PMID- 8500305 TI - Concerning Silverman's suspended judgment article "The most noble goal of medicine" published December 1991. PMID- 8500306 TI - Exclusion of "noncompliant" individuals from clinical trials. PMID- 8500307 TI - Simple explanations for complex systems: surprising and unexpected outcomes. PMID- 8500308 TI - A method for the analysis of randomized trials with compliance information: an application to the Multiple Risk Factor Intervention Trial. AB - The standard approach to analyzing randomized trials ignores information on postrandomization compliance. Application of these methods results in estimates that may lack the desired causal interpretation. We employ a new method of estimation and analyze data from the Multiple Risk Factor Intervention Trial (MRFIT) to estimate the causal effect of quitting cigarette smoking. Our procedure utilizes a method proposed by Robins and Tsiatis and allows us to take advantage of postrandomization smoking history without requiring untenable assumptions about the comparability of compliers and noncompliers. We contrast the performance of our method and the standard intent-to-treat analysis in the MRFIT data and in simulated data in which compliance rates are varied. PMID- 8500309 TI - How many stratification factors are "too many" to use in a randomization plan? AB - The issue of stratification and its role in patient assignment has generated much discussion, mostly focused on its importance to a study or lack thereof. This report focuses on a much narrower problem: assuming that stratified assignment is desired, how many factors can be accommodated? This problem is investigated for two methods of balanced patient assignments; the first is based on the minimization method of Taves and the second on the commonly used method of stratified assignment. Simulation results show that the former method can accommodate a large number of factors (10-20) without difficulty but that the latter begins to fail if the total number of distinct combination of factor levels is greater than approximately n/2. The two methods are related to a linear discriminant model, which helps to explain the results. PMID- 8500310 TI - Recruitment of participants in the Lung Health Study, I: Description of methods. AB - The recruitment experience is described for a large multicenter clinical trial, the Lung Health Study, which required the screening of more than 73,000 male and female smokers aged 35-60. This paper summarizes the plans, methods, and recruiting experience of the 10 participating clinical centers. Recruitment proposals were prepared by each clinical center as part of the contract application process. Recruitment directors and staff were appointed whose primary responsibility was recruitment. Only one clinical center retained its original plan throughout; most clinical centers achieved their recruitment goals by supplementing their originally proposed strategies with one or more methods. The most frequently used methods were worksite, public site, mass mail, telephone, media, and referral strategies. The most significant contributions to the success of the recruitment process were the willingness and initiative of the clinical centers' staff to explore alternative techniques that would take advantage of local circumstances and their ability to incorporate as many workable recruitment methods as necessary to achieve the goal. PMID- 8500311 TI - Design of the Lung Health Study: a randomized clinical trial of early intervention for chronic obstructive pulmonary disease. AB - The Lung Health Study is a multicenter randomized clinical trial. Participants are smokers aged 35-60 with spirometric evidence of moderate lung function impairment. The objective of the trial is to determine whether a program of smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in pulmonary function over a 5-year follow-up period. This paper describes the background, design, sample size (approximately 6000 participants), and power estimates for the trial, as well as the treatment program and the rationale for the choice of inhaled bronchodilator. Plans for analysis of changes in pulmonary function parameters and for analysis of participants' survival and smoking-related morbidity are also discussed. PMID- 8500312 TI - Recruitment of participants in the Lung Health Study, II: Assessment of recruiting strategies. AB - The Lung Health Study (LHS), a multicenter randomized clinical trial of treatment to prevent chronic obstructive pulmonary disease (COPD), recruited, over a 28 month period, 5887 smokers aged 35-60 who had evidence of mild airflow obstruction on pulmonary function testing. The LHS participants were identified from a pool of over 73,000 age-eligible smokers who underwent the initial pulmonary function screening tests. Methods of recruitment in the 10 centers are here classified into five general strategies: worksites, public sites, mail/phone, media, and other. This paper deals with the results of each of these general methods and their effectiveness in producing participants eligible for the study. The most effective strategies proved to be mail/phone and media. Ongoing monitoring and a flexible approach to recruitment characterized the most successful clinics. Over the recruitment period, LHS clinics shifted their emphasis away from worksite and public site strategies and tended to focus on variations of the mail/phone strategy. Female screenees who passed first-screen eligibility criteria were more likely than males to refuse further participation. PMID- 8500313 TI - Monitoring recruitment effectiveness and cost in a clinical trial. AB - Recruitment effort and costs in clinical trials are very often underestimated. As funding constraints increase, more precise estimates of costs as well as methods to monitor effectiveness are needed. However, few studies exist that report recruitment cost effectiveness and costs. The study reported here was developed in Portland, Oregon as an ancillary study to the Lung Health Study. The authors developed a monitoring and evaluation system to track response rates and costs associated with each of five recruitment methods. These methods include (1) media (TV, radio, newspapers), (2) neighborhood promotion, (3) direct mail, (4) worksite promotion, and (5) referral by other study participants. The analysis is limited to a 6-month period (April 1-September 30, 1987) or the middle phase of recruitment. During the study period, 46% were recruited from media, 30% from neighborhood promotion, 1.5% from direct mail, 11% from worksites, and 12% from referrals. Neighborhood promotion and direct mail were least cost-effective, media most cost-effective, with worksite and referral moderately cost-effective. The cost-effectiveness of media promotion is explained in part by the limited number of media sources in Portland, making it possible to reach a large audience with less effort, as well as the ability to provide rapid feedback to media sources. We conclude that the effectiveness of recruitment in a clinical trial is maximized by using multiple overlapping recruitment strategies coupled with a monitoring system that can provide rapid feedback regarding the effectiveness and costs of each strategy. PMID- 8500314 TI - Recruiting healthy participants for a large clinical trial. AB - The Lung Health Study (LHS) is a multicenter randomized clinical trial evaluating treatments for the prevention of chronic obstructive pulmonary disease (COPD). Participants are otherwise healthy smokers with borderline abnormal lung function, who are at relatively high risk of developing COPD. LHS recruiting efforts in the city of Winnipeg, Canada, resulted in the screening of 9,062 people (21% of age-eligible smokers) and randomization of 577 participants. Approximately 50% of the screenees were obtained by direct mail with follow-up telephone calls, while another 14% of the screenees were obtained at worksites. Other recruiting methods included use of mass media, passive displays at community events, and interviewer-aided mall recruiting. Screening rates (percent of the total age-eligible population in Winnipeg screened) were inversely related to age, although eligibility rates were directly related to age. Screening rate was inversely related to indicators of socioeconomic status independent of smoking status. However, randomization rates (percent of the age-eligible population which was randomized) were directly related to socioeconomic status, in part because exclusions for medical reasons were also inversely related to socioeconomic status. Eligibility at initial screening was not related to the recruiting method, but the likelihood of randomizing eligible participants was significantly greater at this clinic for those recruited via mass media and workplace screening than for those recruited by direct mail, and significantly less when recruited at community events. PMID- 8500315 TI - Corneal transplantation with donor corneas stored in moist chamber and chondroitin sulfate-containing medium. AB - Two donor cornea preservation methods, moist chamber and chondroitin sulfate containing medium, were prospectively compared clinically. Paired corneas from 11 donors were divided into two groups: moist chamber group (mean preservation time 9.1 h) and Optisol (Chiron Co., Irvine, CA, U.S.A.) group (mean preservation time 70.8 h). They were compared in terms of their clinical course, corneal thickness, and endothelial density. Recipient age, sex, and diseases were matched between the groups. Nine of 11 corneas in the moist chamber group, and 10 in the Optisol group remained clear at 6 months after surgery. Decreases of the endothelial density were 28.4% in the moist chamber group, and 30.1% in the Optisol group at 6 months after surgery. No differences were found in either endothelial density or corneal thickness throughout the observation period. It was shown that the corneoscleral preservation using chondroitin sulfate-containing medium was as useful as the conventional moist chamber preservation. Considering the requirement for longer donor preservation time, corneoscleral preservation should be adopted in areas other than the United States. PMID- 8500316 TI - Protective properties of viscoelastic substances (sodium hyaluronate and 2% hydroxymethylcellulose) against experimental free radical damage to the corneal endothelium. AB - Hydrogen peroxide (H2O2) has potent oxidant properties due to the action of free radicals (OH.) induced from its degradation. The free radicals specie derived from H2O2 are extremely toxic to the corneal endothelium and quickly induce corneal edema. In the present work, in order to ascertain the endothelial cell protection from viscoelastic substances, we have studied experimental corneal endothelial cell damage caused in the rabbit eye after intracameral injection of different H2O2 concentrations, with and without previous filling and washing out of two widely used viscoelastic substances from the anterior chamber such as 1% sodium hyaluronate (Healon) and hydroxypropylmethylcellulose (HPMC). We observed a dose-dependent endothelial damage in the controls. The experimental groups protected with Healon or HPMC showed statistically fewer corneal endothelial cell lesions than the control group (p < 0.001) for all of the concentrations used. Healon showed superior protective properties than HPMC at higher H2O2 concentrations (100 mM). However, HPMC was superior with 1 and 10 mM peroxide. From this experimental evidence, we conclude that Healon and HPMC are effective as protectors against the corneal endothelial lesions caused by free radicals. This finding may explain some of the beneficial effects of these viscoelastic substances. PMID- 8500317 TI - Artificial tear composition and promotion of recovery of the damaged corneal epithelium. AB - In severe dry eye syndromes the corneal epithelium is compromised with development of punctate erosions and increased permeability. In the present study the ability of artificial tear solutions to promote recovery of the corneal epithelial barrier was determined by measurement of corneal uptake of 5,6 carboxyfluorescein (CF). Corneas of anesthetized rabbits were exposed to 0.01% benzalkonium for 5 min to increase epithelial permeability. The cornea was then exposed to an artificial tear solution for 1.5 h followed by measurement of CF uptake. During exposure to three commercial isotonic, nonpreserved solutions and a solution preserved with polyquaternium-1, CF uptake decreased significantly but did not return to control. No recovery of the epithelial barrier occurred during exposure of corneas to nonpreserved hypotonic solutions. During exposure to an experimental tear solution with an electrolyte composition similar to human tears, buffered with bicarbonate, CF uptake returned to control levels. Bicarbonate is an essential component of this solution because the same formula buffered with borate or without buffer was ineffective in promoting recovery of the damaged corneal epithelium. PMID- 8500318 TI - Recruitment and screening experience for a clinical trial involving tear concentrations of a new drug. AB - The process of recruitment and screening of volunteers for clinical research studies has not been thoroughly evaluated in the ophthalmic literature. The data for the current report were derived from a double-masked randomized clinical trial designed to evaluate and compare the effective tear level concentrations of three topical ophthalmic medications. Subjects were recruited from the general population and were healthy volunteers on no medications. Tear volume was measured by the Schirmer test with anesthesia; acceptable results were in the range of 10-25 mm/5 min. Study enrollment was limited to 32 subjects per week, with a total sample size goal of 320. The study population, 18-45 years of age, consisted primarily of white male college students. Nine hundred fifty-seven volunteers were recruited. Of the 498 of these subjects that reported for screening (52%), 459 (48%) were actually screened, and 320 (33%) were enrolled. The overall prevalence of an abnormal Schirmer test (< 10 or > 25 mm/5 min in either eye) in the screened population was 22%. The frequency of decreased tear production (13%) was slightly greater than that of increased tear production (9%). An abnormal Schirmer test was the primary reason for ineligibility. The completion rate for those enrolled was 96%. This type of information is valuable when designing a clinical trial, especially with regard to budgetary, time table, and sample size estimations. PMID- 8500319 TI - Keratoglobus. AB - Twelve adult patients with keratoglobus are described. Associated ocular conditions included orbital pseudotumor, vernal keratoconjunctivitis in three patients, chronic marginal blepharitis with chronic eye rubbing, and glaucoma after penetrating keratoplasty surgery. Hydrops occurred in 19 of the 21 eyes with keratoglobus. Surgical procedures to treat keratoglobus included large diameter lamellar and penetrating keratoplasty, and limbus-to-limbus epikeratoplasty. PMID- 8500320 TI - Ciprofloxacin ointment versus ciprofloxacin drops for therapy of experimental Pseudomonas keratitis. AB - To compare the efficacy of ciprofloxacin hydrochloride ointment with that of ciprofloxacin drops for treatment of experimental Pseudomonas keratitis, rabbit eyes were infected by intrastromal injection of 10(3) colony-forming units (CFU) log-phase P. aeruginosa. Infected and uninfected eyes were treated with either 0.3% ciprofloxacin ointment applied hourly for 6 h or 0.3% ciprofloxacin drops applied every 15 min for 6 h. Infected eyes treated with the ointment or drop vehicle alone served as placebo controls. Ciprofloxacin ointment significantly reduced the number of viable bacteria (CFU) per cornea more than four logs compared to the placebo control (p < 0.0001). Ciprofloxacin drops significantly reduced the number of bacteria (CFU) per cornea > 7 logs as compared with placebo treated controls (p < 0.0001). Ciprofloxacin ointment may be a useful adjunct to conventional topical drops for therapy of bacterial keratitis. PMID- 8500321 TI - Association of corneal arcus with ultrasonographically assessed arterial wall thickness and serum lipids. AB - Ophthalmological examination was made for 447 hypercholesterolemic middle-aged Eastern Finnish men participating in the Kuopio Atherosclerosis Prevention Study (KAPS) in order to evaluate the prevalence of corneal arcus, its risk factors, and possible association with atherosclerosis. The degree of atherosclerosis was assessed by ultrasonographic examination of carotid and femoral arteries. Corneal arcus in either eye was observed in 51.4% of the participants. Old age and high LDL cholesterol concentration were associated with the presence of corneal arcus. Corneal arcus had a close relationship with ultrasonographically assessed atherosclerosis. PMID- 8500322 TI - Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. AB - In this study we investigated the properties of corneal aldehyde dehydrogenase (ALDH) in keratoconus corneas using various electrophoretic techniques combined with immunochemical and zymographic identification. Normal corneas and other pathologic corneal buttons obtained during keratoplastic surgery were used as a control. A significant (p < 0.001) lower enzymatic activity was found in keratoconus epithelial extracts (3.1 +/- 2.1 IU/mg protein) compared with normal controls (5.5 +/- 2.6 IU/mg protein), whereas no significant differences were observed in the stromal and endothelial extracts. No significant differences were observed for the corneal ALDH thermolability behavior, nor did any marked changes occur in the position of the 54- and 88-kDa species when comparing the pathologic corneas and normal controls. On the other hand, isoelectric focusing analysis showed a different pattern for the pathologic corneas as compared with controls. Moreover, native-polyacrylamide gel electrophoresis analysis showed that normal corneas exhibit three bands, whereas keratoconus and other pathologic corneas only show two bands. The shift from the three-band pattern to the two-band pattern could be reproduced in vitro using reducing agents, such as glutathione. PMID- 8500323 TI - Alkali-degraded cells generate a respiratory burst stimulant for neutrophils. AB - Alkali treatment of whole cornea produces a high molecular weight polypeptide causing a respiratory burst in neutrophils. The current study was conducted to determine if this stimulant could be elicited from cultured or scraped corneal cells (epithelium, keratocytes, or endothelium). Fresh or previously frozen epithelium, endothelium, and stroma were isolated from bovine eyes, alkali treated, and tested for the presence of the respiratory burst stimulant. The same procedure was performed on cultured bovine epithelium, keratocytes, and endothelium. To determine if the stimulant is specific to corneal cells, the component parts of human blood (cellular and extracellular) were separated, treated with alkali, and tested individually. Activation of the respiratory burst of polymorphonuclear leukocytes (PMNs) was used as a marker for the presence of the stimulant. All alkali-degraded cell samples, except red blood cells, produced a respiratory burst when added to viable PMNs. Alkali-treated plasma induced weak stimulation. Bovine corneal epithelium was alkali-treated and separated by high performance liquid chromatography (HPLC) according to molecular size. The stimulant was shown to have a high molecular weight by its recovery in HPLC fraction number 7. These results demonstrate that the PMN stimulant originates from cells. This PMN stimulant is proposed as an inflammatory mediator in the alkali-injured cornea. PMID- 8500324 TI - The effect of aldose reductase inhibitor on the corneal epithelium. AB - Recent studies of diabetic corneal epitheliopathy have shown that diabetic aphakic patients suffer from an enlarged cell area. This study focuses on a 41 year-old diabetic woman whose mean cell area before treatment was 1,101 +/- 275 microns 2. Seven months after treatment it decreased to 723 +/- 253 microns 2. This case shows that through the application of topical aldose reductase inhibitor, the mean cell area in diabetic aphakic patients can decrease toward a normal number. PMID- 8500325 TI - Agenesis of Bowman's layer. A histopathological study of four cases. AB - Congenital absence of Bowman's layer has been described in Peters' anomaly, sclerocornea, and osteogenesis imperfecta type II. More commonly, Bowman's layer is absent secondary to inflammatory or degenerative processes of the cornea. We present three cases of bilateral absence of Bowman's layer in otherwise unremarkable corneas that were unassociated with other ocular or systemic abnormalities. In a fourth case, similar absence of Bowman's layer was present in a patient with osteogenesis imperfecta type III. In all four cases, the absence of Bowman's layer was unassociated with any evidence of scarring or inflammation. By electron microscopy, the stroma was composed of regularly arranged collagen fibers with a uniform fiber diameter throughout. In the case of osteogenesis imperfecta type III, there was mild irregularity of the anteriormost stroma. The lack of inflammation or scarring in these four cases lead us to conclude that they represent a true congenital absence, or agenesis, of Bowman's layer. PMID- 8500326 TI - Bilateral severe keratomalacia after acute pancreatitis. AB - A rare bilateral severe keratomalacia occurred in an emaciated alcoholic, 57-year old white man with acute necrotic pancreatitis. The patient had a 10-year history of chronic alcoholism. Laboratory and clinical findings were consistent with the diagnosis of a fat malabsorptive and malnutrition syndrome secondary to chronic and acute alcoholic pancreatitis. Visual acuity of both eyes was limited to light perception. Bilateral corneal necrosis after acute pancreatitis has not previously been reported. PMID- 8500327 TI - Trimethoprim-sulfamethoxazole for scleritis associated with limited Wegener's granulomatosis: use of histopathology and anti-neutrophil cytoplasmic antibody (ANCA) test. AB - Ophthalmic involvement may be noted in < or = 58% of Wegener's granulomatosis cases, scleritis being one of the most frequent and potentially devastating manifestations. Cytotoxic immunosuppressive drug therapy is effective treatment for this disorder but potentially highly toxic. Recent uncontrolled and anecdotal reports have suggested a possible therapeutic role for a much less toxic agent, trimethoprim/sulfamethoxazole, in limited Wegener's granulomatosis. We report a patient who had a conjunctival nodule and scleritis. Biopsy of the nodule suggested Wegener's granulomatosis, confirmed serologically with serum anti neutrophil cytoplasmic antibody (ANCA) testing. Treatment with oral trimethoprim/sulfamethoxazole was successful. Clinical response was paralleled by normalization of serial anti-neutrophil cytoplasmic antibody titers. This case is the first well-documented ophthalmologic report of limited Wegener's granulomatosis responding to trimethoprim/sulfamethoxazole and adds to the body of literature suggesting a potential role for this drug in selected cases of limited Wegener's granulomatosis. PMID- 8500328 TI - Subconjunctival fibrosis after conjunctival autograft. AB - While largely successful, the use of a conjunctival autograft in the exposed scleral bed following a pterygium excision can result in postoperative complications. We report two cases of a previously undescribed complication: subconjunctival fibrosis at the harvest site of the graft. In one case, the fibrosis caused an asymptomatic, purely cosmetic defect; however, in the other case, the scar tissue constricted the extraocular movement with resultant diplopia. We call attention to this complication as it can affect visual function; we discuss its management and prevention. PMID- 8500329 TI - Design and methods of The Collaborative Corneal Transplantation Studies. The Collaborative Corneal Transplantation Studies Research Group. AB - The Collaborative Corneal Transplantation Studies (CCTS) is a set of two multicenter clinical trials designed to investigate the efficacy of donor recipient human leukocyte antigen matching and crossmatching. High-risk penetrating keratoplasty patients were enrolled through six clinical centers for either the Antigen Matching Study or the Crossmatch Study. All patients were subject to a common set of examinations, treatments, and evaluation procedures. Standard procedures for the identification of high-risk patients, administration of postoperative medications, and recognition and treatment of immunologic allograft reactions were developed and used successfully. These procedures may serve as guidelines for studies in corneal transplantation. Adoption of these methods by other investigators would facilitate evaluation and comparison of results. PMID- 8500330 TI - Biomicroscopic and histopathologic observations after corneal laser photocoagulation in a rabbit model of corneal neovascularization. AB - Corneal neovascularization complicates many anterior segment diseases. Corneal laser photocoagulation using yellow light (577 nm) has been shown to reduce corneal neovascularization. No histopathologic studies of the effects of this treatment on the eye have been reported, however. Target (cornea) and nontarget (iris, lens, retina, and choroid) ocular tissue were studied 1, 24, and 48 h and 5 days after yellow dye corneal laser photocoagulation in a rabbit model of corneal neovascularization. Biomicroscopic examination of the corneas revealed intracorneal hemorrhage in five of 24 (21%) eyes of nonpigmented rabbits. Faint lenticular opacities were observed in two eyes of pigmented rabbits 24 h after laser treatment. Histopathologic examination revealed increased cellularity (neutrophils) (p < 0.005) in the cornea, increasing from 1 h after treatment, peaking 24 h later, and persisting past 5 days. Distortion of the corneal lamellae by red blood cells occurred in eyes in which intracorneal hemorrhage developed. These results indicate that corneal laser photocoagulation using yellow light is a relatively safe procedure for reducing corneal neovascularization. PMID- 8500331 TI - Ascorbic acid and proliferation of cultured rabbit keratocytes. AB - The effect of ascorbate and L-ascorbic acid 2-phosphate (P-Asc), a stable derivative of ascorbate, on the growth of cultured rabbit keratocytes was examined. In a 12-day culture, P-Asc (0.05-0.1 mM) and ascorbate (0.05 mM) enhanced the growth of the cells, whereas 0.1-1.0 mM ascorbate was cytotoxic to the cells. An increase in the concentration of P-Asc up to 1.0 mM resulted in no further change in the cell growth. The effect of 0.1 mM P-Asc was observed after the confluency had been achieved in the culture. The lower toxicity of P-Asc may be due to its stability. The presence of both 0.1 mM P-Asc and mouse epidermal growth factor in the medium stimulated cell growth to a higher degree than each factor alone. The results suggested that these two factors enhance the growth of keratocytes in a different manner. PMID- 8500332 TI - Effects of BSS and BSS+ irrigation solutions on rabbit corneal transendothelial electrical potential difference. AB - Measurements of electrical potential difference across isolated rabbit corneal endothelium (transendothelial electrical potential difference, TEPD) were used to evaluate the effect of two commonly used commercially prepared intraocular irrigation balanced salt solutions, BSS and BSS+, together with our own standard bicarbonate-containing control solution (BS). The highest and most durable TEPD values were obtained by using BSS+; TEPD began at 550 microV, peaked at 600 microV 1 h later, and then decreased slowly down to some 300 microV after about 8 h. Gassing BSS+ with an air/5% CO2 mixture was optimal; gassing it with air reduced the TEPD values slightly, by about 10%. On the other hand, perfusion with BSS gassed with air had a rapid and marked adverse effect; the TEPD, which began at some 500 microV, fell down precipitously to about 50 microV after 1 hour. In contrast, perfusion with BSS on the endothelial side with the addition of BS to the stromal side, both sides being gassed with an air/5% CO2 mixture, maintained the TEPD at levels near those obtained with BSS+. We attribute the adverse effect by BSS to the absence of bicarbonate in it. From these and past results, we conclude that BSS cannot be recommended for intraocular use as a properly balanced saline solution. PMID- 8500333 TI - Effects of growth factors on wound healing in serum-deprived kitten corneal endothelial cell cultures. AB - The influence of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF) I and II on wound healing was investigated in a corneal endothelial system with minimal mitotic activity, using serum-deprived kitten corneal endothelial-cell cultures. After wounding, growth factors were added and wound diameter was evaluated. The DNA synthesis was determined by 3H-thymidine labeling. Wounds did not close in the control cultures grown in serum-free medium without growth factors. The IGF I or II, alone (10 and 100 ng/ml) or added (10 ng/ml) to EGF or bFGF, had no significant effect on wound closure or thymidine uptake. With EGF or bFGF (10 ng/ml), wounds closed after 15 days. Wounds closed after 10 days with EGF or bFGF (100 ng/ml) alone or with the combination of EGF and bFGF (each at 10 ng/ml). Combined EGF and bFGF (each at 100 ng/ml) did not enhance wound closure further. Thymidine uptake was significantly higher in cultures treated with EGF or bFGF (10 ng/ml) than in controls. The uptake could be increased, if both growth factors were combined, but only to the same level achieved with a single factor at 100 ng/ml. This study showed that EGF and bFGF, but not IGF I or II, enhanced wound closure and DNA synthesis in a corneal endothelial cell system that had minimal mitotic activity. PMID- 8500334 TI - A prospective, masked clinical trial of trifluridine, dexamethasone, and artificial tears in the treatment of epidemic keratoconjunctivitis. AB - Epidemics of viral conjunctivitis are a major public health problem in the Far East. No treatment has been shown to shorten the duration of illness. We studied the clinical course of epidemic keratoconjunctivitis in 74 patients during an outbreak of nearly 3,000 cases in late 1988 at a U.S. military base in the Philippines. Patients were randomly assigned to treatment with trifluridine, dexamethasone, or artificial tears, and examined in a double-masked fashion. There was no significant difference between the results of the three treatments. No bacterial cultures were positive. The prompt use of patient isolation, identification of nonadenoviral red eyes, and symptomatic treatment without steroids, antiviral, or antibiotic medication is recommended in cases of epidemic keratoconjunctivitis. This is the largest series of cases of epidemic keratoconjunctivitis with laboratory confirmation reported from the Philippines. PMID- 8500335 TI - Stability and activity of vancomycin in corneal storage media. AB - Gentamicin is the only antibiotic currently added to commercially available corneal storage media. To reduce the potential for bacterial dissemination from donor corneal tissue to the recipient eye, we evaluated the addition of vancomycin to corneal storage media. When added to Dexsol at a concentration of 200 micrograms/ml, vancomycin levels were maintained, showing a 7% decrease in vancomycin concentration per month, measured < or = 90 days after its addition. Human corneas were stored in gentamicin-free Dexsol (Chiron Ophthalmics, Inc., Irvine, CA, U.S.A.) containing 150 micrograms/ml vancomycin. Corneal tissue levels of vancomycin determined by agar diffusion bioassay were 201, 226, 292 micrograms/ml at 1, 3, and 7 days of storage respectively, suggesting that corneal tissue concentrates vancomycin with time. No differences in endothelial cell count or cell death were seen in corneas stored in Dexsol (containing gentamicin) or Dexsol plus vancomycin when followed for < or = 14 days. Vancomycin added to corneal storage media should reduce the potential for endophthalmitis due to gentamicin-resistant organisms. PMID- 8500336 TI - Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action. AB - Bupivacaine is a local ocular anesthetic with a long duration of action when administered by retrobulbar injection. To determine the potential for the use of bupivacaine as a topical ocular anesthetic, the onset and duration of action and toxicity of various concentrations of bupivacaine were studied after instillation in rabbit eyes. The onset and duration of action were not significantly different from that of topical 0.5% proparacaine. Increasing the pH of the bupivacaine solution from 5.7 to 6.5 nearly doubled the duration of action, but the increase was not sufficient to be clinically important. Slit lamp biomicroscopic examination and scanning electron microscopy showed that bupivacaine was less toxic to the corneal epithelium than 0.5% proparacaine. Healing after keratectomy was significantly more rapid in eyes treated with 0.75% bupivacaine, compared with eyes treated with 0.5% proparacaine. These results suggest that bupivacaine may be less toxic to the corneal epithelium than proparacaine and could be clinically useful for topical ocular anesthesia, particularly if pharmacologic modifications can increase the duration of anesthesia provided by this drug. PMID- 8500337 TI - Corneal asphericity and visual function after radial keratotomy. AB - Corneal asphericity was measured before and after surgery in 81 radial keratotomy eyes. Asphericity was calculated between keratoscope rings 2 and 9, representing corneal diameters of 2.3 mm and 7.6 mm. Statistical methods were used to assess the relationship between postoperative asphericity and undilated, uncorrected visual acuity. Smaller radial keratotomy clear zones resulted in greater negative asphericity after surgery (R = 0.74, p < 0.0001). For eyes with smaller clear zones of < 4.0 mm, postoperative negative asphericity was high (mean -6.44). Eyes in this smaller clear zone range had better uncorrected visual acuity if they possessed higher levels of negative asphericity (Mann-Whitney U test, p < 0.0001). The study suggests that eyes with smaller clear zones gain a beneficial increase in depth of field as the degree of negative asphericity increases. The study offers this as one reason that radial keratotomy patients with residual refractive error often have better uncorrected visual acuity than expected. PMID- 8500338 TI - Ultraviolet light-induced pathology in the eye: associated changes in ocular aldehyde dehydrogenase and alcohol dehydrogenase activities. AB - Adult male C57BL/6J inbred mice were subjected to ultraviolet radiation (UVR) exposure (302-nm peak wavelength; average intensity 282 microW/cm2) for 1 h and monitored for ocular aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activity changes over a period of 25 days. Dramatic reductions in activities were observed by 4-6 days postexposure, resulting in enzyme levels of 15-16% of control animals. Major decreases in corneal enzyme levels were predominantly responsible for these changes. Ocular morphology was observed throughout using a photoslit-lamp biomicroscope, with maximum corneal clouding occurring at days 4-6. These data support earlier proposals for major roles for these corneal enzymes in assisting the cornea in protecting the eye against UVR induced tissue damage. PMID- 8500339 TI - Fibroblast growth factor-1 receptor messenger RNA expression in corneal cells. AB - The polymerase chain reaction (PCR) and hot-blotting methods were used to identify fibroblast growth factor (FGF) receptor-1-specific messenger ribonucleic acid (mRNA) sequences in cDNA samples prepared from human corneal endothelial cell cultures with proliferative and senescent morphology, an ex vivo corneal epithelium sample, two primary corneal epithelial cell cultures, two third passage corneal epithelial cell cultures, and two stromal fibroblast cultures. The PCR primers used in this study distinguished mRNAs coding for three aminoterminal motifs (alpha, beta, and gamma) of the FGF receptor-1 that are derived by alternative splicing from a single genomic sequence. Messenger RNA molecules coding for FGF receptor-1 amino-terminal motif were detected in corneal endothelial and epithelial cells. The alpha and beta amino-terminal motif, but not the gamma amino-terminal motif, mRNAs were detected in stromal fibroblasts. The gamma motif lacks a known signal sequence for membrane translocation and is thought to represent an intracellular form of the FGF receptor-1. Identification of mRNA coding for FGF receptor-1 along with the previous identification of basic FGF mRNA and protein in corneal endothelial, epithelial, and stromal fibroblast cells suggests an autocrine and/or paracrine role for basic FGF in the physiology of the cornea. PMID- 8500340 TI - Successful treatment of microsporidial keratoconjunctivitis with topical fumagillin in a patient with AIDS. AB - There recently have been several reports of microsporidial keratoconjunctivitis caused by the organism Encephalitozoon hellem. However, treatment of this infection has been largely ineffective. We report a case of a 35-year-old Hispanic woman with AIDS and E. hellem keratoconjunctivitis confirmed with light, electron, and immunofluorescence microscopy that resolved promptly with topical fumagillin, a crystalline antibiotic with proven efficacy against Encephalitozoon species. No corneal or systemic toxicities were noted using the dosage and preparation employed (10 mg/ml suspension in balanced salt solution). An easily prepared, topical fumagillin suspension appears to be a safe, effective treatment for E. hellem keratoconjunctivitis. PMID- 8500341 TI - Recurrent corneal infections in a patient with the acquired immunodeficiency syndrome. AB - A 29-year-old female intravenous drug abuser infected with the human immunodeficiency virus suffered recurrent, bilateral corneal infections over an 11-month period. Multiple infectious organisms were responsible, including capnocytophaga species, Candida albicans, Staphylococcus aureus, coagulase negative staphylococcus, and a-streptococcus. One eye was eviscerated because of corneal perforation and loss of vision; the second eye has maintained good vision. Predisposing factors usually associated with corneal infections were absent. Treatment was complicated by extremely poor patient compliance, ongoing intravenous drug abuse, and concurrent multiple extraocular medical problems. PMID- 8500342 TI - Dellen causing disappearance of Vogt's limbal girdle (II): A compressive phenomenon? AB - The cornea remains clear and avascular partly as a result of the compactness of the stromal lamellae. Loosening of these lamellae promotes loss of corneal transparency and peripheral vascularisation. Conversely, increased compactness of corneal tissue may possibly result in resorption of certain peripheral opacities. We report a case in which increased corneal compactness, produced by dellen formation, resulted in the disappearance of a type II Vogt's limbal girdle. PMID- 8500343 TI - Enterococcal infectious crystalline keratopathy. AB - Two patients developed infectious crystalline keratopathy (ICK) 9 and 11 months after penetrating keratoplasty. In both cases, cultures yielded enterococcus sensitive to vancomycin. The first patient developed diffuse loss of corneal and conjunctival epithelia after 24 h of treatment with vancomycin eyedrops, whereas the second patient did not respond after 14 days of topical vancomycin therapy. Both patients eventually required penetrating keratoplasty. Enterococcus is a ubiquitous bacterium resistant to many antibiotics that should be suspected of causing ICK. PMID- 8500344 TI - Sleep problems in childhood. AB - Sleep, like eating and toileting, is an individual physical requirement that changes with time as the child matures. Although much about a child's sleep is biologically determined, extrinsic factors, usually through the parents, also mold the child's sleep behavior. Normal sleep for a child is restful to the child and not excessively disruptive to others. Sleep problems interfere with the quality of the child's sleep and frustrate or frighten caretakers. Several sleep problems have their origins in normal sleep behavior from an earlier age. Some, the parasomnias, are caused by self-limited biologic diatheses. Many sleep problems have psychosocial triggers. Sleep disorders only rarely are a primary medical problem that is adequately treated with medication (e.g., narcolepsy). Good history-taking, often accompanied by diary-keeping, will usually identify the problem--the first step in effective treatment. Treatment of a sleep disorder in the pediatrician's office can start with educating caretakers about normative sleep for the age of the child and providing information regarding the cause and natural course of the problem. Treatment also may involve behavioral or psychological intervention or both, but medication is generally not indicated. When needed for short-term treatment, mild sedatives such as antihistamines are used most often. More serious sleep or behavioral problems should be acknowledged by the primary care pediatrician, followed by referral to an appropriate specialist. Inquiry into a child's sleep habits at each well-child visit, coupled with appropriate anticipatory guidance, could make an important contribution to the child and family by preventing problems with sleep and identifying sleep problems early in their evolution. Pediatricians and parents can work together to help children develop good sleep habits that fulfill the child's evolving sleep requirements within the context of the family's needs and expectations. PMID- 8500345 TI - A new rapid air-drying technique for scanning electron microscopy using tetramethylsilane: application to mammalian tissue. AB - A new rapid air-drying technique for scanning electron microscopy (SEM) with results comparable to critical point drying (CPD) has been developed. In earlier studies a trematode parasite and a fungus were used as test specimens. Here the application of the new method for SEM of some mammalian tissue is described. The method is based on drying the tissues from an organo-silicon compound whose physical and chemical properties make it the most appropriate fluid for tissue drying. PMID- 8500346 TI - Comparison of the antiproliferative effects of colon mitosis inhibitor, thyroliberin and the somatostatin analog octreotide on rat colonic mucosal epithelial cells. AB - The effects of colon mitosis inhibitor (CMI), thyroliberin (TRH), and the somatostatin analogue octreotide (SMS 201-995) on rat colonic mucosal epithelial cell proliferation were studied. As an index of cell proliferation the incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used. It was found that all three peptides inhibited the colonic mucosal epithelial cells proliferation, but the time course of inhibition was different. The effect of SMS 201-995 occurred 12 h after the peptide injection, while CMI and TRH suppressed the proliferation after 24 h. These observations suggest that the mechanisms of the antiproliferative actions of somatostatin and of related tripeptides CMI and TRH are different. PMID- 8500347 TI - Heat shock genes in the willistoni group of Drosophila: induced puffs and proteins. AB - Seven species of the willistoni group of Drosophila were comparatively analysed for their response to heat shock and anoxia, both at the transcriptional (induced puff) and translational (induced protein) levels. The number of induced puffs varied among the species, but were concentrated at chromosomes 3 and XR. One puff present under control (25 degrees C) conditions was found to increase in size in response to stress in all species. Proteins of 83 and 70 kD were induced in all species in response to heat shock, as well as proteins of 50 and 32 kD, but not reported for other species of Drosophila under similar conditions. The number and size of the small heat shock proteins induced, as expected, showed considerable interspecific variability. PMID- 8500348 TI - Induction of micronuclei in peripheral blood lymphocytes of patients treated for rheumatoid or osteo-arthritis of the knee with dysprosium-165 hydroxide macroaggregates or yttrium-90 silicate. AB - The advantages of radiation synovectomy, using preparations containing dysprosium 165 (Dy-165), over conventional materials based on yttrium-90 (Y-90) include a more ideal spectrum of decay energies, and a much shorter half-life permitting quicker and more efficient treatment. A new therapeutic agent, Dy-165 hydroxide macroaggregates, has been developed for the treatment of arthritis making use of these advantages. As part of a clinical trial of this material 42 patients were examined for micronucleus frequency in their peripheral blood lymphocytes prior to, and 2 weeks after, radiation synovectomy using Dy-165 hydroxide macroaggregates or Y-90 silicate. In the majority of patients from each treatment group no significant increase in micronucleus frequency was observed. This indicates that in these cases leakage of material from the site of treatment was not resulting in detectable irradiation of circulating cells irrespective of the choice of radiopharmaceutical. The maximum increase in micronucleus frequency observed corresponded to a radiation dose to circulating cells of approximately 0.3 Gray. PMID- 8500349 TI - Taurine distribution in different cat muscles as visualized by immunohistochemistry: changes with stimulus state. AB - The distribution of endogenous taurine in the cardiac pectinate muscle, the intestinal wall smooth muscle and in nine striated muscles of the cat was studied by immunohistochemistry. It was found that taurine-like immunoreactivity (TLI) is distributed homogeneously in the cardiac and smooth muscles selected where it is present in every single fibre. In contrast, TLI appeared unevenly distributed in eight out of nine skeletal muscles, the soleus being atypical. Under resting conditions, TLI is present in only a portion of the fibre population, the proportion being specific for each muscle. Under nerve stimulation the TLI negative/positive ratio increased, suggesting release activity, while an opposite trend occurred after denervation. Glutamate-like immunoreactivity (GLI), although present in every fibre, showed a stronger reaction in those fibres positive to taurine, suggesting parallel movements of both amino acids. Results are discussed in terms of two functional possibilities. PMID- 8500350 TI - Detection of DNA strand breaks induced by hydroxyl radicals in nuclear and chromosomal chromatin by electron microscopy. AB - Chinese hamster Don cells were treated with 10 mM hydrogen peroxide. DNA strand breaks induced by hydroxyl radicals were amplified in 3' termini by an exonuclease III digestion, resulting in single stranded DNA motifs. In situ detection of these motifs was performed on chromatin fibres of isolated whole mounted nuclei and chromosomes by a random priming procedure, using biotinylated dUTP which bound a gold-tagged streptavidin. This approach facilitated the location of hydroxyl radical induced DNA breaks, specifically on 20-30 nm diameter chromatin fibres, by transmission electron microscopy. PMID- 8500351 TI - In situ hybridization localizes the human OTF3 to chromosome 6p21.3-->p22 and OTF3L to 12p13. AB - Otf-3 (Octamer-binding transcription factor 3) is an octamer binding protein encoded by the murine gene Otf-3. Otf-3 belongs to a multigenic family and maps to the mouse Chromosome 17 between the Q and T regions within the major histocompatibility complex (MHC). We report the mapping of the human homologue: OTF3, to human chromosome 6p21.3-->p22 within or close to the human MHC class I region. Furthermore, one OTF3-like copy (OTF3L) is localized to 12p13. PMID- 8500352 TI - Chromosome studies in hypoptopomatinae (Pisces, Siluriformes, Loricariidae). II. ZZ/ZW sex-chromosome system, B chromosomes, and constitutive heterochromatin differentiation in Microlepidogaster leucofrenatus. AB - Cytogenetic analysis of two local populations of Microlepidogaster leucofrenatus showed a basic diploid chromosome number (2N) of 54 in both populations. Some fishes were found to have a 2N = 55 or 56 chromosomes due to the presence of one or two large heterochromatic B chromosomes. Specimens of M. leucofrenatus from the Poco Grande stream had 24 metacentrics, 24 submetacentrics, four subtelocentrics, and one submetacentric homomorphic pair in males and one submetacentric/subtelocentric heteromorphic pair in females, whereas individuals of this species from the Marumbi River had 22 metacentrics, 24 submetacentrics, four subtelocentrics, two acrocentrics, and one submetacentric/subtelocentric heteromorphic pair in females. The occurrence of the heteromorphic pair in the females was due to the presence of an extra C-banded segment on the W chromosome. Ag-NORs in both populations were located interstitially on the short arm of the largest metacentric pair. The Poco Grande population had less constitutive heterochromatin than did the Marumbi River population. The speciation process in this fish species is discussed on the basis of heterochromatin distribution. PMID- 8500353 TI - Meiotic abnormalities in hybrid mice of the C57BL/6J x Mus spretus cross suggest a cytogenetic basis for Haldane's rule of hybrid sterility. AB - Light- and electron-microscopic analyses of chromosomal pairing and recombination in F1 and first-backcross generation mice of the C57BL/6J x Mus spretus cross revealed a variety of meiotic irregularities that could contribute to meiocyte loss and infertility. Pachytene anomalies included univalency, partially paired bivalents, homolog-length inequalities, nonhomologous pairing, and associations of asynapsed autosomal segments with the X chromosome. These phenomena were most prevalent in F1 males, which are invariably sterile. Although F1 females were qualitatively fertile, breeding data indicated significant reproductive impairment. Molecular analyses of X-linked and pseudoautosomal loci in sterile and fertile backcross males revealed that the failure of X-Y pairing and recombination is correlated with heterozygosity within the pseudoautosomal regions of the X and Y chromosomes. In addition to impairing fertility, the synaptic disturbances (such as localized asynapsis and nonhomologous pairing) observed in F1 individuals can potentially alter recombinational patterns, thereby contributing to the genetic-map distortion observed with this interspecific cross. Together, the cytogenetic and reproductive data suggest that sex-related differences in the gametogenic process, quantitative differences in the incidence of synaptic irregularities in female and male meiosis, and phenomena associated with the X and Y chromosomes comprise the etiological basis of the sex-biased F1 sterility. The differential gender-related effects of these cytogenetic phenomena may constitute the underlying basis of Haldane's rule in mammals. PMID- 8500354 TI - Repeated primed in situ labeling: formation and labeling of specific DNA sequences in chromosomes and nuclei. AB - A new version of our previously published PRINS (PRimed IN Situ labeling) method is presented. It represents a significant improvement in the detection of specific DNA sequences in situ. The idea is to perform the reaction repeatedly, rather than just once. This change of strategy results in a localized accumulation of sequence-specific labeled DNA, resulting in up to a 15-fold amplification of the signal as compared to the standard PRINS method. Interestingly, the retention of the labeled DNA is so good that it stays within the chromosomal band where it is synthesized, provided that the reaction is not performed an excessive number of times. The key trick is the performance of the procedure on small glass slides in PCR tubes, thereby avoiding the use of cover slips. In addition, use of the small glass slides seems to give less variance when the signals are quantified in a fluorescence microscope. PMID- 8500355 TI - Assignment of genes for interleukin-8 receptors (IL8R) A and B to human chromosome band 2q35. AB - The human genes encoding the interleukin 8 receptors type A and B were assigned to chromosome 2 by polymerase chain reaction amplification and by Southern analysis of a panel of human x rodent somatic cell hybrid DNAs. The IL8R genes were further localized by in situ hybridization to band 2q35. PMID- 8500356 TI - The gene coding for erythrocyte protein band 7.2b (EPB72) is located in band q34.1 of human chromosome 9. AB - Human erythrocyte integral membrane protein band 7 (also termed protein 7.2b or stomatin) is involved in the Na+/K+ permeability of red cells. A cDNA clone coding for this protein was used as a probe to determine the chromosomal localization of the gene (EPB72). Southern blot analysis of somatic cell hybrid DNA panels localized the human EPB72 gene to chromosome band 9q34.1. PMID- 8500357 TI - Sex chromatin in hair roots--25 years later: fluorescence in situ hybridization of hair root cells for detection of numerical chromosome aberrations. AB - The applicability of fluorescence in situ DNA hybridization to hair root preparations for the detection of numerical chromosome anomalies is demonstrated. This simple method yields a high number of scorable nuclei, allowing rapid identification of epithelial cell chromosome composition. In clinical genetics, this technique may become useful in cases where other types of cells are difficult to obtain. PMID- 8500358 TI - Arthroplasty in the sequelae of congenital hip dysplasia. AB - The authors report their experience in the surgical treatment of the sequelae of congenital hip dysplasia, more specifically, 125 arthroplasties performed in 116 patients, with specific reference to the technical difficulties encountered and the various surgical methods used. This review suggests that prosthetization yields a high percentage of good results (77%) and constant remission of pain. Nonetheless, joint function, particularly when motion was severely compromised before surgery, or when dislocation was very severe (Crowe grades III and IV), is not always restored. PMID- 8500359 TI - Carpal tunnel syndrome in hemodialyzed patients. AB - A total of 18 hemodialyzed patients submitted to surgery for the treatment of carpal tunnel syndrome are examined. In all of the cases pre- and postoperative EMG and biopsy were performed. Six months after surgery all of the patients showed improved pain symptoms, in 66% there was good recovery of sensitivity and of the function of the hand: these results were confirmed by EMG monitoring. In all of the biopsies amyloid deposits, particularly diffused in the tendinous and nervous sheaths, were observed. At 2-year follow-up 75% of the patients showed recurrence of pain symptoms. Thus, surgery does not seem to definitively resolve symptoms. PMID- 8500360 TI - Ancient schwannoma of the motor branch of the median nerve: a clinical case. AB - The authors present a case of ancient schwannoma of the motor branch of the median nerve. An accurate peroperative diagnosis was not possible despite the use of MRI. Sectioning of the nerve was required as the tumor could not be enucleated. PMID- 8500361 TI - The "Tour Eiffel" double Rush nail in the treatment of fractures of the lower limb. AB - The authors reviewed 73 patients treated by delayed osteosynthesis with a "Tour Eiffel" double Rush nail. The cases involved fracture of the lower third of the femur in 20 patients, fracture of the proximal third of the tibia in 24 cases, and fracture of the distal third of the tibia in 29. The results indicate the effectiveness of the method, despite the fact that its use was reduced as a result of the introduction of the Grosse-Kempf nail. This is however the method of choice for tibial meta-diaphyseal fractures associated with fracture of the tibial plateaux and complex and comminuted fractures of the distal fourth of the tibia. Moreover, this method must be used three-six weeks after the fracture, when the callus formation is in progress. PMID- 8500362 TI - The anchor nail in osteosynthesis of fractures of the humerus. AB - Osteosynthesis with a humeral anchor nail may be listed along with other methods of intramedullary fixation for the treatment of diaphyseal fractures. The authors report their experience with 33 cases of humeral fractures treated between July 1987 and July 1991. Results were excellent in 61% of the cases, good in 24%, and fair in 15%; no particular complications were reported. The authors believe that the anchor nail constitutes a system of osteosynthesis involving only a small amount of trauma, and allowing for positive elastic stability for the consolidation of the fracture, as well as being a sufficiently safe system so that immobilization in plaster may be avoided. When compared with other systems of intramedullary fixation, the anchor nail is more effective than the Rush nail from a mechanical point of view, and the Kuntscher nail from a biological one. PMID- 8500363 TI - The correction of anterior flat foot in Apert's syndrome. PMID- 8500364 TI - A case of traumatic plastic deformation of the forearm in the adult. AB - Traumatic plastic deformation is a rare occurrence in childhood and is exceptional during adult age. The authors report one case of the lesion occurring in a patient aged 20 years; they emphasize the need for adequate treatment, and formulate a pathogenetic hypothesis with a biomechanical basis. PMID- 8500365 TI - Fracture of the coracoid process associated with fracture of the clavicle: description of a rare case. AB - The authors report on a case of fracture of the coracoid process associated with fracture of the clavicle. Open reduction and internal fixation of the coracoid process lead to a good clinical and radiographic outcome. PMID- 8500366 TI - Anesthesiologic findings in surgery for the treatment of trauma of the pelvis. AB - The authors discuss the numerical increase in fractures of the acetabulum and the extent of surgical indications for their treatment, emphasizing the modernness and the usefulness of methods used to save blood in this type of surgery, which often involves a considerable loss. Out of 150 operations performed between 1985 and 1990 for trauma of the pelvis, 35% of the patients was not transfused with homologous blood, 25% was transfused with 1 U, 40% with several units (4.7 U on the average). Generally, the average quantity of erythrocytes transfused per patient was 2 U (440 ml). PMID- 8500367 TI - The gamma nail and the compression-sliding plate in the treatment of pertrochanteric fractures: anesthesiologic aspects. AB - The authors compare the results obtained in a group of 100 patients submitted to pertrochanteric osteosynthesis during the year 1991 (50 with a gamma nail and 50 with a compression-sliding plate) based on parameters of anesthesiology. The same type of anesthesiology was used in all 100 of the patients, as similar were the general clinical conditions of the patients, ASA classification, and the mean value of preoperative hemoglobin. The gamma nail proved to be preferable in terms of a shorter amount of time required for surgery, a minor loss of blood intra and postoperatively, and minor incidence of complications. PMID- 8500368 TI - Patellar realignment in recurrent subluxations and dislocations: long-term results. AB - A total of 41 patients affected with recurrent subluxations or dislocations of the patella treated with different surgical methods between 1972 and 1981 were examined. Radiographic and clinical monitoring according to Crosby-Insall in 35 patients ranges from 10 to 20 years, with the following results: excellent: 17%; good: 69%; fair: 14%; poor: 0; recurrent dislocations or subluxations: 0. PMID- 8500369 TI - Medical malpractice involving colon and rectal disease: a 20-year review of United States civil court litigation. AB - To determine objectively the causes of malpractice litigation involving colon and rectal disease, a retrospective review was undertaken of all cases tried in the U.S. federal and state civil court system over a 21-year period from 1971 through 1991. Ninety-eight malpractice cases were identified from a computerized legal data base, involving 103 allegations of negligence. Allegations fell into five major categories: 1) failure to timely diagnose disease, principally colorectal cancer and appendicitis (n = 44/103; 43 percent); 2) iatrogenic colon injury (n = 25/103; 24 percent); 3) iatrogenic medical complications during diagnosis or treatment (n = 16/103; 15 percent); 4) sphincter injury with fecal incontinence, resulting from anorectal surgery or midline episiotomy (n = 10/103; 10 percent); and 5) lack of informed consent, especially regarding extent of procedures or risk of endoscopy (n = 8/103; 8 percent). These data may aid in design of risk prevention strategies related to the diagnosis and treatment of colorectal disease. PMID- 8500370 TI - Surgery for symptomatic hemorrhoids and anal fissures in Crohn's disease. AB - This study was undertaken to determine the outcome of surgery for symptomatic hemorrhoids and anal fissures in patients with known Crohn's disease. Seventeen patients underwent surgery for symptomatic hemorrhoids. Fifteen of these 17 patients' wounds healed without complication. Twenty-five patients underwent 27 operations for anal fissures. Twenty-two of these patients had uncomplicated wound healing by two months. Long-term follow-up, which was at a mean of 11.5 years in the hemorrhoid patients and 7.5 years in the fissure patients, revealed that only three patients required proctectomy, none as a direct result of surgery. Patients with severe symptoms secondary to anal fissures and hemorrhoids, who are known to have Crohn's disease and who cannot be controlled with conservative medical management, may undergo surgery on a highly selective basis when the disease is in the quiescent state. Proctectomy is not an inevitable outcome. PMID- 8500371 TI - Malignant potential in flat elevations. AB - Ninety-nine colonoscopically removed flat elevations were examined. They were divided into two groups: Group 1--flat elevations 1 to 5 mm in diameter (55 cases)--and Group 2--flat elevations 6 to 10 mm in diameter (44 cases). Group 2 had a higher percentage of adenomas (86.4 percent) than Group 1 (67.3 percent). In adenoma cases (flat adenomas), Group 2 tended to show a higher degree of dysplasia. The rates of mild and moderate dysplasia were 83.8 percent and 16.2 percent in Group 1 vs. 1.70 percent and 13.2 percent in Group 2, respectively. Group 2 contained six cases (15.8 percent) of intramucosal carcinoma (severe dysplasia), while there were no cancer cases in Group 1. Both malignancy rate and degree of dysplasia were size dependent; the larger the lesion the more severe the dysplasia. Our study also revealed that small flat elevations tend to contain higher numbers of nonneoplastic lesions than do larger lesions. Increased detection of nonneoplastic lesions seems to have contributed to an overall decline in the malignancy rate of flat elevations in recent reports. PMID- 8500372 TI - Intrarectal ultrasound in the evaluation of perirectal abscesses. AB - Experience with intrarectal ultrasonography (IRUS) is limited for the evaluation of perianal sepsis. The purpose of this article is to report our experience with IRUS in evaluating 24 cases of suspected perianal abscess and fistula. IRUS was performed intraoperatively using a Bruel & Kjaer (Model #1846; Naerum, Denmark) endoanal ultrasound scanner with a 7-MHz transducer. After completion of the IRUS, careful anorectal examination and appropriate surgical therapy were performed. At surgery, 19/24 patients were found to have perirectal abscesses, with all 19 cases correctly identified preoperatively by IRUS. In 12 cases (63 percent), IRUS correctly defined the relationship between the abscesses and sphincters by Parks' classification. At surgery, internal openings of fistulous tracts were found in 14/19 cases, but IRUS identified only 4/14 (28 percent). In 6/24 cases, IRUS and clinical evaluation did not demonstrate a perirectal abscess. The role of IRUS in the evaluation of perirectal abscess is evolving. Certainly, uncomplicated abscesses can be managed without ultrasonography. However, IRUS can be an adjunct to careful evaluation of complex perianal suppurative disease. PMID- 8500373 TI - Morphology of dynamic graciloplasty compared with the anal sphincter. AB - Dynamic graciloplasty for fecal incontinence includes gracilis muscle transposition around the anal canal as a new sphincter and subsequent electrical stimulation. The aim of electrical stimulation is to transform the gracilis fast twitch, "fatigue-prone" fibers into slow-twitch, "fatigue-resistant" fibers to achieve a sustained tonic contraction. The latter is considered essential for sphincter function. Therefore, the following features of transposed gracilis muscle morphology were studied in nine patients before and after electrical stimulation: 1) the percentage of Type I fibers, 2) the lesser diameter of these fibers, and 3) the positive collagen staining area. Furthermore, the external and sphincter and gracilis muscle histology was investigated in six autopsy cases. The mean percentage of Type I, slow-twitch, fatigue-resistant fibers in transposed gracilis muscle increased from 46 percent before electrical stimulation to 64 percent (P < 0.01, paired Student's t-test) after electrical stimulation. The mean lesser diameter of these fibers did not change significantly (from 32 to 29 microns), and the mean percentage of collagen increased from 4 percent before electrical stimulation to 7 percent (P < 0.01) afterward. The external sphincter in cadavers demonstrated a predominance of Type I fibers (80 percent) with a lesser diameter of 23 microns and a high percentage (12 percent) of collagen. Gracilis muscle histology was uniform at six different sample sites in these cadaver dissections. We conclude that electrical stimulation induces histologic changes in transposed gracilis muscle, allowing this muscle to function as an external anal sphincter. PMID- 8500374 TI - Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. AB - From 1980 to 1985, 471 patients with resectable rectal and rectosigmoid cancer were randomly allocated to receive either preoperative short-term high-dose irradiation (25.5 Gy in one week) for all patients or prolonged postoperative radiotherapy (60 Gy in seven to eight weeks) only for patients with a Dukes B or C lesion. After a minimum follow-up of five years, the local recurrence rate was statistically significantly lower after preoperative than after postoperative radiotherapy (13 percent vs. 22 percent; P = 0.02). No difference in overall survival was noted (P = 0.5). To evaluate possible late side effects on the bowel, urinary bladder, or skin after surgery and additional preoperative or postoperative radiotherapy, all patients included in the randomized trial, together with 58 patients from a preceding pilot study with the same preoperative regimen, were studied in a prolonged follow-up program. The hospital files of all patients were re-examined. Of the patients who were carefully examined, 176 had a survival exceeding five years and 19 had a survival exceeding 10 years. Overall, 7 percent (33/464) either were operated upon or have had a radiologic diagnosis of small bowel obstruction: 14/255 (5 percent) after preoperative irradiation, 14/127 (11 percent) after postoperative irradiation, and 5/82 (6 percent) after surgery alone. The cumulative risk of developing a bowel obstruction was significantly increased after postoperative radiotherapy. Among the 98 patients alive after preoperative irradiation, significant morbidity from the bowel was noted in 11 patients, from the urinary bladder in two, and from the skin in six. In the postoperatively treated group of 34 patients, the bowel, urinary bladder, and skin morbidity were significant in five, two, and five patients, respectively. Corresponding morbidity in 44 nonirradiated patients was seen in five, one, and two patients, respectively. It is concluded that preoperative, short-term, high-dose radiotherapy decreases the local recurrence rate relative to postoperative radiotherapy, with no indications of increased late morbidity after a follow-up of 5 to 10 years. PMID- 8500375 TI - Role of the seton in the management of anorectal fistulas. AB - PURPOSE: To identify the incidence of major fecal incontinence and recurrence after staged fistulotomy using a seton. METHODS: A five-year retrospective chart review of 116 patients (70 males and 46 females) ranging in age from 18 to 81 years (mean, 42 years), in whom setons were placed as part of a surgical procedure for anorectal fistulas, was carried out. Follow-up ranged from 2 to 61 months (mean, 23 months). RESULTS: Setons were employed to identify and promote fibrosis around a complex anorectal fistula as part of a staged fistulotomy in 65 patients (56 percent). Other indications for seton placement included 24 women with anteriorly situated high transsphincteric fistulas (21 percent) and three patients with massive anorectal sepsis (floating, freestanding anus) (2.5 percent). In addition, setons were used to preclude premature skin closure and promote controlled long-term fistula drainage in 21 patients with severe anorectal Crohn's disease (18 percent) and in three patients with AIDS (2.5 percent). Major fecal incontinence (requiring the use of a perineal pad) occurred in five patients (5 percent), and recurrent fistulas were noted in three (3 percent). CONCLUSIONS: Staged fistulotomy using a seton is a safe and effective method of treating high or complicated anorectal fistulas. PMID- 8500376 TI - Randomized trial comparing diathermy hemorrhoidectomy with the scissor dissection Milligan-Morgan operation. AB - Twenty consecutive patients (12 male and 8 female) with second-degree, third degree, or thrombosed hemorrhoids were randomly allocated to undergo either diathermy hemorrhoidectomy (n = 10) or a scissor dissection Milligan-Morgan hemorrhoidectomy (n = 10). No significant difference was found in the postoperative pain score between the groups. On a scale of 0 to 10, the mean daily pain score in the diathermy group was 4.0, and it was 4.1 in the scissor dissection group. Nor was there any significant difference in the length of inpatient stay (diathermy group, 3.5 days; scissor dissection group, 4.0 days) or in the time between the operation and the first bowel action (diathermy group, 2.0 days; scissor dissection group, 3.0 days). Diathermy hemorrhoidectomy has no significant advantage over the scissor dissection classical Milligan-Morgan hemorrhoidectomy. PMID- 8500377 TI - Quality of life after restorative proctocolectomy with a pelvic ileal reservoir compares favorably with that of patients with medically treated colitis. AB - There remains some reluctance among physicians to refer patients for restorative proctocolectomy (RP). They argue that their patients would be worse off with a pouch because of the attendant problems of urgency and frequent bowel actions. The aim of this study was to compare quality of life in patients who had undergone RP with that of patients with ulcerative colitis on long-term medical treatment. A detailed questionnaire and the Hospital Anxiety and Depression (HAD) test were completed by 103 patients who had undergone RP and by 95 patients with ulcerative colitis on medical treatment and in remission attending a gastroenterology clinic. Patients with a pouch had a greater frequency of bowel action [five times per 24 hours (range, 4-7) vs. two times per 24 hours (range, 1 3); P < 0.001] but less urgency of defecation [12/103 (11.7 percent) vs. 69/95 (72.6 percent); P < 0.001] than patients with medically treated colitis. Efficiency of evacuation, discrimination between flatus and feces, use of perianal pads, and perianal soreness were similar. Use of antidiarrheal medication was more common in the pouch group [53 of 103 patients (51.5 percent) vs. 3 of 95 patients (3.2 percent); P < 0.05], whereas use of topical steroids was more common in medically treated patients [40 of 95 patients (47.1 percent) vs. 9 of 103 patients (8.7 percent); P < 0.05]. Limitation of social activity and HAD scores were significantly higher in medically treated patients. Quality of life for patients with a pouch appears to be as good as that for patients with medically treated colitis. PMID- 8500378 TI - MMPI assessment of patients with functional bowel disorders. AB - This prospective study was undertaken to assess personality differences among patients with chronic pelvic floor disorders. Sixty patients (43 females and 17 males) of a mean age of 58 (range, 33-87) years with fecal incontinence (n = 19), constipation (n = 30), or levator spasm (n = 11) had a mean duration of symptoms of 35 (range, 2-50) years. The Minnesota Multiphasic Personality Inventory (MMPI) was utilized for psychologic assessment for all patients prior to treatment. Mean scores for scales 1 (hypochondriasis), 2 (depression), and 3 (hysteria) were significantly elevated for the levator spasm group (71, 75, and 73, respectively). A similar pattern was seen for the constipation group, where the mean scores for scales 1 and 2 were significantly elevated (70 and 74, respectively) with a moderate elevation on scale 3 (68). The hypochondriasis (1), depression (2), and hysteria (3) scales are referred to as the "neurotic triad," and profile patterns such as these indicate that these subjects may manifest their psychologic distress as physical symptoms. By contrast, the fecal incontinence patients were within the normal range on all scales. The information from these MMPI profiles can be used to understand the personality and emotional composition of these patients to assist in their evaluation and treatment. PMID- 8500379 TI - Determination of inflammatory bowel disease activity by breath pentane analysis. AB - PURPOSE: Quantitative determination of breath pentane, an alkane generated by peroxidation of cellular fatty acids, has been used as a noninvasive determinant of inflammation. Herein we report the first examination of the relationship between breath pentane and intestinal inflammation in humans. METHODS: Patients (N = 33), either with a known history of inflammatory bowel disease (IBD) with symptoms of relapse or with no known history of but having symptoms consistent with IBD, were evaluated with indium-111-labeled leukocyte imaging to assess the presence of active inflammation. At the time of the indium scan, the exhaled breath of the patients was obtained via a collecting tube. Gas chromatography was used to quantify the pentane content, and these values were compared with graded indium scans. RESULTS: The range of breath pentane found in our population (36 determinations in 33 patients) was from 0 to 38.4 nmol/l of exhaled air. For patients with negative scans, the mean pentane was 2.1 nmol/l, for intermediate scans 3.1, for positive scans 4.3, and for nonintestinal nuclide imaging 5.5 [P = 0.005 by analysis of variance (ANOVA)]. CONCLUSIONS: We have previously demonstrated the correlation of breath pentane with gross and histologic evidence of intestinal inflammation in a rodent colitis model. This current study also demonstrates that pentane analysis can be correlated with inflammatory bowel disease activity in humans. PMID- 8500380 TI - Colonic necrosis following sodium polystyrene sulfonate (Kayexalate)-sorbitol enema in a renal transplant patient. Report of a case and review of the literature. AB - The authors present the case of a patient who developed near total colonic necrosis shortly after renal transplantation. The onset of symptoms was temporally related to the administration of sodium polystyrene (Kayexalate; Sanofi Winthrop Pharmaceuticals, New York, NY)-sorbitol enemas for treatment of hyperkalemia. Three similar cases have been reported in the literature. The presence of uremia and the use of sorbitol appear to be common denominators in the pathophysiology of this complication. It is suggested that Kayexalate sorbitol enemas be avoided in renal transplant patients. PMID- 8500382 TI - Third level hemodynamics: guiding clinical decisions. PMID- 8500381 TI - Fibrin sealing of irradiated bowel anastomoses. PMID- 8500383 TI - Therapeutic listening: key intervention for several nursing diagnoses. AB - Listening is the intervention of choice for several nursing diagnoses common to critically ill patients. Yet, because the patients often cannot talk long and nurses are busy, listening can be difficult to implement in critical care. PMID- 8500384 TI - Meeting the challenge. PMID- 8500385 TI - Comparison of blood pressure measurement methods in critically ill children. AB - Blood pressure measurement has been studied by many researchers, resulting in the development of BP measurement recommendations and guidelines for various age groups and clinical situations. Blood pressure measurement in critically ill children has not been studied extensively and requires additional research to validate the efficacy of various BP measurement methods in this unique patient population. In this study, the differences among direct, oscillometric, and doppler blood pressure measurements were compared in twelve critically ill children. PMID- 8500386 TI - Infective endocarditis: a challenging diagnosis. AB - The critical care nurse plays a key role in the management and care of the patient with Infective Endocarditis. The nurse's sensitive assessment of post operative cardiac surgery patients helps to identify this complication in the early stages so that early antibiotic therapy can improve outcomes for patients with this complication. Likewise, the nurse's assessment which uncovers a history of recent dental techniques or drug abuse helps identify this complication in newly-admitted patients. By administering and evaluating the success of antibiotic therapy the nurse helps the patient combat the Infective Endocarditis. PMID- 8500387 TI - Withdrawing treatment from the hopelessly ill. Part 1: The ethical case. AB - The ICU exists so that critically ill patients can receive highly technical, specialized care which will support physiologic function until recovery can occur. When the patient cannot sustain life without the assistance of technology, and recovery is known to be unlikely, withdrawal of treatment may be appropriate. Nonetheless, withdrawal of life-sustaining treatment is often complex ethically and emotionally. The following case submitted by a DCCN reader illustrates the challenge of treatment withdrawal issues in critical care. PMID- 8500388 TI - Strategies for writing a competitive research abstract. AB - This article focuses on the process of preparing research abstracts for submission to scientific meetings of professional organizations. Perspectives on the process of specifying an abstract's focus, choosing a scientific meeting, selecting the type of presentation, developing an abstract, and writing an abstract in its form are presented. PMID- 8500389 TI - Denial: an adaptive response. AB - Denial is a common nursing diagnosis for cardiac patients; yet, not all denial situations are bad. This author describes when denial is actually a successful coping mechanism and describes how to decide when to intervene and when to allow the patient to use this coping technique. PMID- 8500390 TI - Infection control: a career option for the critical care nurse. AB - Infection control is a nursing career option that offers variety, autonomy, expert status, and lifelong learning. The critical care nurse's experience with invasive procedures, knowledge of physiology, and readiness to handle the unexpected are an excellent background for this role. PMID- 8500391 TI - Thrombotic thrombocytopenia purpura: nursing during the acute phase. AB - Thrombocytopenia and anemia related to Thrombotic Thrombocytopenia Purpura cause multi-system complications requiring critical care nursing during the acute stages. The nurse's detailed assessment helps identify or prevent many of these complications. PMID- 8500392 TI - Differentiating chest pain: advanced assessment techniques. AB - Clinical reasoning of the critical care nurse is enhanced by use of the "PQRST" Mnemonic in differentiating cues related to emerging patterns of chest pain. The subjective expression of chest pain can vary depending on one's cultural background. Nurses who become aware of their own cultural beliefs and values are more sensitive to the cultural influences in patients' responses. PMID- 8500393 TI - Unit-based product evaluation: Part 1: Comparison of pulmonary artery and tympanic membrane temperature. AB - Although new products go through rigorous study before FDA approval, it is still important to evaluate the product for use with your nursing protocols and patient population. This author describes a product evaluation project conducted in the critical care units at her agency and gives advice on how to set up similar product evaluation studies in your setting. PMID- 8500394 TI - Unit-based product evaluation: Part 2: Planning product evaluation studies. AB - This second article in this set gives you advice on how to set up your own product evaluations. Critical care nurse managers, educators, and Clinical Nurse Specialists, researchers, and even staff nurses are planning product evaluation studies to determine what equipment best meets the needs of the nurses and patients in their units. If you are interested in evaluating a product you are considering or have recently acquired, here are tips on how to develop a unit based product evaluation. PMID- 8500395 TI - Mandatory HIV testing: a timely controversy. AB - Incidence of infection with the human immunodeficiency virus (HIV) has increased to epidemic proportions. Strategies are needed to prevent transmission of the virus. One strategy, mandatory HIV testing of nurses, is controversial. Both sides of this issue are debated in this article. PMID- 8500396 TI - [Truth at the bedside. Ethical problems in the nursing professions]. PMID- 8500397 TI - [The first duty of freedom is to set itself limits]. PMID- 8500399 TI - [On necessary renounciations in old age]. PMID- 8500398 TI - [Reverence for life. Thoughts on Albert Schweitzer's ethics]. PMID- 8500400 TI - [Care versus self-determination. Thoughts on generally valid ethics that can be realized in everyday life]. PMID- 8500401 TI - [Teaching of ethics. Problems in the introduction of ethics]. PMID- 8500402 TI - [Ethics education in nursing--presentation of problems]. PMID- 8500403 TI - [Reasons for a separate ethics course in nursing education]. PMID- 8500404 TI - [Concept of a teaching unit "Introduction to Ethics"]. PMID- 8500405 TI - ["Teachers' Training Course"--a work shop meeting for the teaching of ethics in the healing professions]. PMID- 8500406 TI - [Academy for ethics in medicine]. PMID- 8500407 TI - [Limitations in medicine. Challenge and threat]. PMID- 8500408 TI - [Ethical requirements in the care of the elderly]. PMID- 8500409 TI - [The problem of truth disclosure in pediatric oncology]. PMID- 8500410 TI - [Limits to the obligation of medical treatment in severely disabled newborns. Revised form of 1992 Einbeck recommendations of the German Society for Forensic Law of 1986]. PMID- 8500411 TI - [Computer-assisted realization of the rules for nursing personnel. Report of experiences in data interpretation by bar code]. PMID- 8500412 TI - [A Q fever epidemic in Berlin. The epidemiological and clinical aspects]. AB - An epidemic of Q fever in Berlin affected at least 80 patients (45 females, 35 males; age range 1-75 years). Sheep were identified as the focus of infection: they had been brought to a veterinary clinic because of nonspecific symptoms. The peak incidence of the infection was in April and May, 1992. Most of the patients were staff or students at the veterinary clinic. This is the most northern and, at the same time largest, Q fever epidemic recorded in Germany over the last 28 years. The complement fixation reaction (CFR) was not helpful diagnostically in the acute stage of the disease as it remained negative in the first 14 days (CFR < or = 1:5). Most of the patients had sudden fever to over 40 degrees C, severe headache and dry cough. Pulmonary infiltrates were seen in the chest radiograph of 8 of the 10 patients presented in this contribution. Auscultation was largely negative. Two patients had signs of hepatic involvement (GPT as high as 71 U/l). The drug of choice was doxycycline at a dosage of 200 mg twice daily for 14 days. PMID- 8500413 TI - [Extrathoracic prolapse of the pulmonary parenchyma after a bout of coughing with spontaneous serial rib fractures]. AB - A 54-year-old man with an feverish infection of the lower respiratory tract developed severe pain in the lateral and basal part of the left thorax after a severe coughing bout. A haematoma occurred at the site and it looked as though tissue evaginated at that spot on coughing and pressing. The clinical diagnosis was pneumonia and abnormal mobility of the eighth to tenth rib on the left with crepitations. The chest radiograph demonstrated fractures of these ribs and extrathoracic sickle-shaped collection of air in the left laterobasal area. Computed tomography additionally showed prolapse of pulmonary tissue on pressing. This was thus a case of "cough fracture", complicated by herniation of lung tissue. There was no evidence of incarceration of lung tissue and, as the patient was very obese, surgery was not indicated. Symptoms and signs of infection regressed on symptomatic and antibiotic treatment. The rib fractures healed as pseudoarthroses. Lung tissue prolapse on pressing was still present 3 months later. PMID- 8500414 TI - [The diagnosis and therapy of childhood speech disorders]. PMID- 8500415 TI - [The diagnosis of reactive arthritis. The possibilities and limits]. PMID- 8500416 TI - [Nocturnal asthma: circadian rhythm or sleep-related breathing disorders?]. PMID- 8500417 TI - [Vasovagal syncope after vascular puncture]. PMID- 8500418 TI - [Autonomic diabetic neuropathy of the gastrointestinal tract]. PMID- 8500419 TI - [The etiology of essential hypertension]. PMID- 8500420 TI - [The epidemiology of stomach carcinoma from the surgical viewpoint. The results of the German Stomach Carcinoma Study 1992. The German Stomach Carcinoma Study Group]. AB - In a prospective multi-centre study data were collected on 1,999 patients (1273 men, 726 women; mean age 62.3 [19-99] years) with gastric carcinoma, admitted to one of 19 surgical departments in Germany between 1.4. 1986 to 30. 6. 1989. Previously treated patients as well as those with synchronous or metachronous tumours and carcinoma of the gastric stump had been excluded. The resection rate for gastric carcinoma was 82.7%, i.e. resection was no longer possible because of the advanced tumour stage in nearly 20%. The tumour was located in the upper third of the stomach in 30%, the antrum in 26.3%. An intestinal type of growth was present in 51.9%. An early carcinoma was diagnosed in 16.9% of operated patients; it had already metastasized to regional lymph nodes in 16.5%. Nearly 70% of patients with resectable tumours had metastases to the regional lymph nodes, with distant metastases in 30%. An advanced tumour stage (UICC stage IIIB or IV) was present in 43%. Exclusively surgical treatment is not effective in these cases. PMID- 8500421 TI - [Late valvular dysfunction after mechanical mitral valve replacement]. AB - 14 years after a Bjork-Shiley prosthesis had been implanted because of combined mitral failure, a 68-year-old woman complained of progressive decrease of physical powers combined with apnoea, retrosternal feeling of pressure and tachycardiac atrial fibrillation. Five weeks later, onset of cardiac decompensation with dyspnoea at rest and signs of congested pulmonary circulation were noted. Echocardiography revealed stenosis of the mitral valve prosthesis. The patient was operated on two days later. It became evident that the patency of the prosthesis was greatly obstructed by connective tissue which had proliferated at the ventricular side. The original valve prosthesis was replaced by a St. Jude bi-leaflet valve. The likelihood of prosthesis dysfunction must always be considered if there is a deterioration in the patient's condition after a long uncomplicated postoperative course following cardiac valve replacement. PMID- 8500422 TI - [The cellular mechanisms of atherogenesis]. PMID- 8500423 TI - [The immune defect in kidney failure. I. The clinical manifestations]. PMID- 8500424 TI - [Hepatitis B vaccination in the immunosuppressed]. PMID- 8500425 TI - [Ochronosis]. PMID- 8500426 TI - [The therapy and prevention of gastroduodenal lesions]. PMID- 8500427 TI - [The Saccharomyces boulardii therapy of HIV-associated diarrhea]. PMID- 8500428 TI - [Venous thrombosis and hereditary protein C deficiency]. PMID- 8500429 TI - The chromosome 6p epilepsy locus: exploring mode of inheritance and heterogeneity through linkage analysis. AB - Juvenile myoclonic epilepsy (JME) is a common form of adolescent-onset, generalized epilepsy. JME is genetically linked to the HLA locus on chromosome 6. Families of JME patients also have a significant recurrence of other forms of generalized epilepsy. We used the linkage data to investigate the mode of inheritance of JME and the associated electroencephalographic (EEG) traits at the HLA-linked locus. We investigated how robust the linkage results were when we changed the assumptions of mode of inheritance and penetrance and whether absence and clonic-tonic-clonic in JME families are influenced by the same gene locus as JME. Our results show that the finding of linkage is stable within a wide range of assumptions of penetrance and mode of inheritance, and that the EEG traits seen in unaffected family members reflect the actions of the same gene that is involved in the expression of JME. Our data also suggest that the same locus is responsible for non-JME forms of epilepsy seen in JME families, and that either different doses of the disease allele at the JME locus may lead to different epilepsy phenotypes or that another locus influences the final disease phenotype. PMID- 8500430 TI - Progressive myoclonus epilepsies: clinical and genetic aspects. AB - The progressive myoclonus epilepsies (PMEs) are a group of rare genetic disorders previously shrouded in nosological confusion. Recent advances have clarified the features of these disorders and provided a rational approach to diagnosis. The major causes of PME are now known to be Unverricht-Lundborg disease, myoclonus epilepsy ragged-red fiber (MERRF) syndrome, Lafora disease, neuronal ceroid lipofuscinoses, and sialidoses. Over the past 3 years, a series of molecular genetic findings have further refined the understanding of the PMEs. The specific mutation responsible for many cases of MERRF has been identified, and the genes for Unverricht-Lundborg disease and for juvenile neuronal ceroid lipofuscinosis have been linked to chromosomes 21 and 16, respectively. Although the PMEs are among the rarest of the inherited epilepsies, because of molecular genetic discoveries they may soon be the best understood at the neurobiologic level. PMID- 8500431 TI - Animal models of inherited epilepsy. AB - A significant proportion of the childhood epilepsies have a genetic component. Therefore, animal models that can be bred for seizure expression may provide important information regarding the mechanisms by which molecular defects result in the neuronal hyperexcitability states collectively termed "epilepsy." Because of the rate and ease of breeding, rodent models are the most commonly used. The genetically epilepsy-prone rat has motor seizures in response to auditory stimuli. It is likely that the seizures are generated in the inferior colliculus because of an abnormality in the noradrenergic system. The seizure predisposition is inherited as an autosomal dominant trait. The genetic absence epilepsy rat has age-related spontaneous seizures characterized by motor arrest and head drops that are correlated with generalized spike-wave on the electroencephalogram (EEG). The seizure generating mechanism appears to be located in the lateral thalamic nuclei. The epileptic mongolian gerbil demonstrates behavioral arrest followed by myoclonic, tonic, and tonic-clonic seizures in response to unfamiliar environments. The underlying neuroanatomy involves hippocampal-cortical interactions indicative of a partial epilepsy. The tottering mouse has absence and myoclonic seizures, a 6- to 7-Hz ictal spike-wave EEG, and noradrenergic hyperinnervation that are linked to a mutation on chromosome 8. Hippocampal network hyperexcitability has been found with normal neuronal intrinsic properties. Stargazer is a mouse mutant with almost identical clinical and electrographic features as found in tottering. However, the genetic defect is located on chromosome 15 and no abnormalities of norepinephrine have been discovered. The El mouse demonstrates ictal automatisms in response to vestibular stimulation. Metabolic and structural abnormalities have been found in the hippocampus. Linkage to chromosomes 9 and 2 have been reported recently. The dilute brown agouiti mouse demonstrates motor seizures in response to auditory stimuli. Chromosomes 4 and 17 are linked to seizure expression. Thus, a variety of models exist to study the genetic, biochemical, structural and electrophysiological mechanisms that underlie the predisposition and expression of the inherited epilepsies. PMID- 8500432 TI - The absence epilepsies. AB - Four syndromes comprise the absence epilepsies. Each is classically associated with the absence seizure, although other syndromes also have absence attacks as part of their repertoire. The most common syndrome is childhood absence epilepsy; it usually occurs in the age range of 6-7 years. The absence seizures may occur many times daily, and the electroencephalographic (EEG) characteristics are the most typical of the absence epilepsies. The second form of absence epilepsies is juvenile absence epilepsy; it begins near puberty and may represent a continuum from the childhood form. Myoclonic seizures are more common than in the childhood form, and the spike-wave discharges in the EEG are often faster than that seen in childhood absence epilepsy. The third form of absence epilepsy is juvenile myoclonic epilepsy, characterized especially by myoclonic jerks in the morning; these attacks occasionally progress to generalized tonic-clonic seizures. The final form of absence epilepsy is epilepsy with myoclonic absences, a rare disorder with a specific form of absence seizures. The absence seizure itself is observed to a greater or lesser extent in all of these syndromes. This seizure is a curious event, and its causes are poorly explained by current knowledge of the fundamental mechanisms of the epilepsies. Although the etiology of the absence seizure at a biochemical level is unknown, some studies suggest that certain low threshold calcium ion currents (T currents), which are partially controlled by GABA-B mechanisms, may activate burst firing of thalamic neurons, initiating an absence seizure. The evidence of a genetic predisposition for the absence epilepsies is overwhelming.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500433 TI - Benign focal epilepsies of childhood. AB - Until relatively recently, genetic influences in partial seizures were thought to be of minimal importance. However, with further identification of childhood benign partial seizures it is becoming clear that inheritance plays a major role in the pathogenesis of these seizures. Diagnostic criteria proposed for benign partial seizures include absence of neurologic or intellectual deficits, family history of epilepsy, onset of seizures after age 2 years, stereotyped brief seizures, frequent nocturnal occurrence, spontaneous remission in adolescence, and electroencephalograms (EEGs) demonstrating spikes with a distinctive morphology and localization superimposed on normal background activity. The two most commonly described benign partial epilepsies of childhood are benign Rolandic epilepsy (BRE) and benign occipital epilepsy (BOE). Both disorders begin in childhood, are associated with characteristic EEG patterns, have seizures that are easily controlled with medication, often are familial, and have an excellent prognosis. The other benign partial seizure disorders in children that have been described are not as well studied as BOE and BRE, and the role of inheritance pattern, if any, is less clear. PMID- 8500434 TI - Metabolic and degenerative diseases associated with epilepsy. AB - Identifying the specific etiology of epilepsy is often difficult. The search for the cause often leads the clinician to suspect inborn errors of intermediary metabolism and other degenerative metabolic diseases. Although these uncommon diseases are often difficult to determine, a correct diagnosis is critical for treatment and genetic counseling. A review of the relevant biochemistry will aid in understanding the pathophysiology of seizures in these conditions. The stream lined approach to the initial laboratory evaluation that is offered will enable the clinician to screen for most metabolic and degenerative diseases that are associated with epilepsy. PMID- 8500435 TI - Epilepsy in the setting of neurocutaneous syndromes. AB - The neurocutaneous syndromes are characterized by congenital dysplastic abnormalities involving the skin and nervous system. The commonest neurocutaneous syndromes manifesting epilepsy are tuberous sclerosis and the Sturge-Weber syndrome. Neurofibromatosis and other lesser-known entities, such as epidermal nevus syndrome, are also known to be accompanied by epilepsy. These syndromes are not related to one another. This article reviews what has been learned about the epileptic syndromes in these disorders. PMID- 8500436 TI - Hypochondriasis and somatization in college women: a personal projects analysis. AB - Although the descriptive features of hypochondriasis and somatization have been widely studied, the motivational correlates (goal representations) of individuals manifesting abnormal illness patterns have not been considered. The Personal Projects Analysis method (Little, 1983) was used to contrast the health and nonhealth goals of female undergraduates. Subjects selected 10 goals for evaluation along a series of dimensions. When health pursuits alone were examined, hypochondriasis on the Minnesota Multiphasic Personality Inventory was found to correlate directly with goal appraisal dimensions subsumed by an anxiety absorption factor and inversely with dimensions characterizing rewardingness, thus suggesting a negativity of health goal construal. Somatizers also pursued more health-related projects than did nonsomatizers; nonhealth goal cognition did not relate as strongly to hypochondriasis. Finally, using discriminant function analysis, goal representations were shown to significantly and substantially differentiate somatizers from nonsomatizers. PMID- 8500437 TI - Risky decision making and allocation of resources for leukemia and AIDS programs. AB - Traditional judgment and decision-making paradigms were expanded to include differential reactions to persons with leukemia or AIDS. Experiments 1 and 2 adopted Tversky and Kahneman's risky-decision-making task and found support for different value functions for the 2 patient groups when choosing between treatment programs. From these results, the subjective value of saving a fixed number of lives appears to be greater for persons with leukemia than for persons with AIDS. Experiment 3 provided additional data concerning differential perceptions of the causes of AIDS. This proved to be a useful means of classifying Ss who did and did not devalue the lives of persons with AIDS. PMID- 8500438 TI - Stress and affiliation: hospital roommate effects on preoperative anxiety and social interaction. AB - Fifty-three preoperative men were studied who were assigned to a hospital roommate who varied in terms of the similarity of the roommate's health problem and surgical status. The similarity of a roommate's particular type of health problem to that of the patient exerted little detectable influence. However, patients assigned to a preoperative roommate were more anxious compared with those assigned a postoperative or nonsurgical roommate. Affiliation was also significantly greater with fellow preoperative roommates compared with postoperative roommates. The possibility that the obtained roommate effects on anxiety are mediated directly by affiliation is explored. Additional mechanisms and theoretical implications for basic research involving social comparison, stress, and affiliation relationships are discussed. Practical considerations for hospital policy also are considered. PMID- 8500439 TI - Short-term effects of occupational stressors on daily mood and health complaints. AB - This article related daily changes in 2 job conditions, workload and social interaction with co-workers and supervisors, to daily mood and health complaints. Fifty-two air traffic controllers (ATCs) completed measures of subjective well being and perceived job conditions on 3 consecutive days; objective indicators of daily workload (air traffic volume and visibility at the airport) were also obtained. The results indicate that increases in job stressors are associated with a same-day deterioration in physical and psychological well-being. On days in which workload was perceived to be high, ATCs reported more health complaints and moods that were more negative and less positive. On days in which there was greater air traffic volume (objectively measured), ATCs reported moods that were more negative. On days in which interactions with co-workers and supervisors were described as more distressing, ATCs reported moods that were more negative and less positive. PMID- 8500440 TI - Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students. AB - The relationship of individual differences in repressive coping styles with differences in antibody titer to Epstein-Barr viral capsid antigen (EBV-VCA) were investigated in a normal, healthy college population made up of people previously exposed to EBV. Each of 54 1st-year undergraduates completed a battery of physical-status questions and items pertaining to potential behavioral immunomodulatory confounds, along with the Taylor Manifest Anxiety Scale (T-MAS) and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Ss reporting high and middle levels of anxiety had higher antibody titers to EBV, suggesting poorer immune control over the latent virus, as compared with the low-anxious group. Similarly, high-defensive Ss had higher antibody titers than their low-defensive counterparts, and neither group differed from the middle group. PMID- 8500441 TI - Physicians' liking for their patients: more evidence for the role of affect in medical care. AB - Correlates of physicians' liking for their patients were examined among 17 internists at a health maintenance organization and 530 of their patients 70 years of age and older. Analyses were conducted for the entire sample as well as for individual physicians, whose results were combined by meta-analysis. Both kinds of analysis showed that patients were more liked when they were in better health (based on psychometric measures of social, emotional, functional, and overall self-rated health) and when they were more satisfied with their care. In addition, male patients were liked more than female patients, and physicians who were female and less experienced liked their patients more. PMID- 8500442 TI - Substance use and memory for health warning labels. AB - This article reports the relationship between substance use and memory for health warnings for cigarettes, smokeless tobacco, and alcohol. Measures of substance use and recognition memory for warning labels were collected from 2 samples of college students (n = 288 and n = 243). It was hypothesized that if health warnings were noticed and remembered, then users, because they were often exposed to the warning labels, would have more accurate memory for the risks written on the containers of these products than nonusers. Prior research had not confirmed this relationship. In Study 1, a statistically significant correlation was obtained between use and recognition memory for both cigarettes and smokeless tobacco. The effects for cigarettes and smokeless tobacco were replicated in Study 2 and observed for alcohol as well. PMID- 8500443 TI - Sleep disorders in children. AB - Many children experience some type of sleep problem. Often, these are transient problems with no long-lasting sequelae. But in certain cases, sleep problems may significantly impact on functioning and well-being. Sleep disorders in children can be classified into two major categories. Dyssomnias include those disorders that result in difficulty either initiating or maintaining sleep or involve excessive sleepiness. Parasomnias are disorders that disrupt sleep after it has been initiated but do not result in complaints of insomnia or excessive sleepiness. Even though sleep disorders in children are common, not enough is known. This article reviews the dyssomnias and parasomnias experienced by children, discusses methodological limitations of the studies reviewed, and presents future directions for research in this field. PMID- 8500444 TI - Contributions to patient adherence: is it time to share the blame? AB - Poor adherence to treatment is well recognized and contributes significantly to treatment failures in medical care. Studies examining contributing factors have focused predominantly on the patient. Studies examining provider influences have primarily examined communication styles or educational practices. Di Matteo et al. show, in this issue of Health Psychology, that other characteristics of the provider may influence patient behavior. Particularly interesting is the finding that baseline adherence predicts adherence 2 years later. Although this study opens the door to an examination of provider characteristics and their influence on patient behavior, care needs to be taken to avoid too rapid an acceptance of the discrete findings. The study used self-report by interview, a measure that can be significantly biased. However, this study provides future avenues to explore using more objective measures of patient adherence. PMID- 8500445 TI - Physicians' characteristics influence patients' adherence to medical treatment: results from the Medical Outcomes Study. AB - The influence of physicians' attributes and practice style on patients' adherence to treatment was examined in a 2-year longitudinal study of 186 physicians and their diabetes, hypertension, and heart disease patients. A physician-level analysis was conducted, controlling for baseline patient adherence rates and for patient characteristics predictive of adherence in previous analyses. General adherence and adherence to medication, exercise, and diet recommendations were examined. Baseline adherence rates were associated with adherence rates 2 years later. Other predictors were physician job satisfaction (general adherence), number of patients seen per week (medication), scheduling a follow-up appointment (medication), tendency to answer patients' questions (exercise), number of tests ordered (diet), seriousness of illness (diet), physician specialty (medication, diet), and patient health distress (medication, exercise). PMID- 8500446 TI - Symptom representations and affect as determinants of care seeking in a community dwelling, adult sample population. AB - The cognitive and emotional determinants of health-care utilization were assessed for middle-aged and older adults matched on age, gender, and health status. Both members of a pair were interviewed when either initiated a medical visit. Interviews were based on a self-regulatory model that assumed that Ss would use symptoms to create and update representations and coping procedures. Care seekers reported more symptoms than did matched controls but did not report more symptoms than did matched controls with new symptoms. The mere presence of atypical symptoms was insufficient to trigger care seeking. Care seeking is driven by well developed representations of a serious health threat, perceptions of inability to cope with the threat, advice to seek care, and life stress. PMID- 8500447 TI - Menstrual cycle and premenstrual syndrome: modifiers of cardiovascular reactivity in women. AB - Fifteen women prospectively diagnosed with PMS and 15 non-PMS women were each tested twice for cardiovascular stress reactivity and behavioral performance, once during the follicular phase and once during the luteal phase of their cycle. Although blood pressure and heart rate responses to stress did not differ across the menstrual cycle in either group of women, for the non-PMS women, differences in hemodynamic responses were observed across the 2 phases. The luteal phase was associated with greater stroke volume responses and lesser vascular tone. For the PMS women, none of their cardiovascular measures differed across their cycle. Instead, these women showed significantly attenuated blood pressure and heart rate responses compared with non-PMS women, irrespective of cycle phase. PMID- 8500448 TI - Role of health locus of control beliefs in cancer screening of elderly Hispanic women. AB - This study examined the health locus of control beliefs of elderly Hispanic women and relation between frequency of breast self-examination (BSE), attention to health-related information, and recency of Pap smear and physician breast examination. As hypothesized, holding a belief that health outcomes are controlled by oneself (internal control) was positively related to screening behaviors over which one has a high degree of personal control, such as frequency of BSE and attention to health-related information. Belief that medical professionals control health outcomes was positively related to physician dependent screening activities, such as recency of Pap smear and physician breast exam. The findings confirm the specificity of association between health control beliefs and preventive behaviors and demonstrate the importance of these beliefs in medical screening by Hispanic women. PMID- 8500449 TI - Autonomy, relatedness, and the initiation of health risk behaviors in early adolescence. AB - This study examined the relationships among sociodemographic characteristics, family processes, and the initiation of health risk behaviors in early adolescence. Subjects were 189 6th and 7th graders from a public middle school. A path-analytic model was used to analyze data. Results showed that students who received autonomy support from parents were less likely to initiate sexual intercourse. Students who were emotionally detached from their parents were more likely to fight and use substances. Those who were emotionally detached tended to come from families with low levels of cohesion and acceptance. Sociodemographic variables, such as family structure, gender, and ethnicity, had both direct and indirect effects on health risk behaviors, but the indirect effects were quite small. PMID- 8500450 TI - Women's decision making about mammography: a replication of the relationship between stages of adoption and decisional balance. AB - The motivational and cognitive processes of behavior change in the area of screening mammography were investigated. A total of 676 women, 40 to 79 years old, were recruited for telephone interview through random selection from designated census tracts and were asked questions that assessed mammography stage of-adoption and decisional balance constructs from the trans-theoretical model of behavior change. Two definitions of stage of adoption were used. Analysis of covariance showed that a history of regular screening and an intention to continue having the exam were associated with a more favorable decisional balance. Results replicated a prior investigation and demonstrated the usefulness of stage of adoption and decisional balance as guides for designing stage-matched interventions to increase rates of mammography. PMID- 8500451 TI - Factors associated with severity of depression and high-risk sexual behavior among persons diagnosed with human immunodeficiency virus (HIV) infection. AB - Whereas some people appear to cope after learning that they have human immunodeficiency virus (HIV) infection, others experience depression and suicidal ideation. In this study, 142 persons with HIV infection were administered the Center for Epidemiological Studies Depression Scale (CES-D). High levels of depression were predicted by lower perceived social support, attributions that health was influenced more by chance, high-risk sexual behavior practices, and greater number of HIV illness symptoms and greater duration of time knowing of one's own positive serostatus. Ongoing high-risk sexual behavior practices were predicted by higher levels of recreational drug use and of depression. These findings highlight the need for improved mental health services for persons with HIV conditions. PMID- 8500452 TI - Effects of treatment for intestinal parasites and malaria on the cognitive abilities of schoolchildren in Zaire, Africa. AB - Ninety-seven Zairian schoolchildren were evaluated for cognitive ability, health status, and quality of home environment. Children successfully treated for serious types of chronic intestinal parasites demonstrated significant improvements in K-ABC Spatial Memory, supporting this task as one of the more sensitive measures to changes in general health and neurological integrity. These findings were not obtained for successful treatment of low-grade malaria infection. Children initially negative for intestinal parasites tended to come from more economically and socially favorable home environments. They also demonstrated more dramatic improvements in visual-spatial analysis tasks. The implication is that the home environment factors conducive to chronic infestation with intestinal parasites are markers for favorability of the developmental milieu affecting long-term intellectual development. PMID- 8500453 TI - Decision-making orientation and AIDS-related knowledge, attitudes, and behaviors of Hispanic, African-American, and white adolescents. AB - How adolescents' personal sense of directedness (i.e., peer, parent, or self directed orientation) affects the decision-making processes of adolescent students regarding AIDS-related knowledge, attitudes, beliefs, behaviors, and skills (KABBS) is examined. The sample consisted of 10th-grade students in 8 public high schools (N = 2,515) in Dade County (greater Miami), Florida. The findings showed that decision-making orientation and directedness was a significant predictor of AIDS-related KABBS of adolescents. Overall, the level of AIDS-related KABBS that were associated with low risk was found significantly more often among self-directed students and least often among peer-directed students. The findings of this study suggest that future preadult health-risk research should incorporate the concept of differences of information processing across adolescents. PMID- 8500454 TI - Correct and incorrect interpretations of correlations between risk perceptions and risk behaviors. AB - Correlations between risk perceptions and risk behaviors are used by investigators to answer 2 important and easily confused questions: Are individuals' perceptions of their personal risk accurate, correctly reflecting their precautions and their risk-increasing behaviors? and Does recognition of high personal risk cause people to adopt precautions to reduce that risk? Researchers who use survey data to investigate these questions often look at the wrong correlations to get their answers. Furthermore, as members of a population adopt precautions and change their risk status, correlations between perceived risk and risk behavior in this population also change. A mathematical model of precaution adoption--allowing a bidirectional relationship between perception and behavior--is used to illustrate the different correlations between risk perception and risk behavior that can be examined and the changes in correlations that can occur with the passage of time. Recommendations are provided concerning the correlations most appropriate for answering each of the 2 preceding questions. Which correlation is appropriate to answer the second question varies depending on whether a study is begun before people have taken precautions or after ample time to take precautions has already passed. PMID- 8500455 TI - An investigation of the validity of the quality of Well-Being Scale with pediatric oncology patients. AB - The usefulness of the Quality of Well-Being scale (QWB) in a sample of pediatric cancer patients was investigated. The parents of 30 children who were 4 to 18 years old and who were being treated for cancer, were administered the QWB. Performance status ratings from the parents and physician, toxicity ratings, treatment information, and routine laboratory values were also collected. Correlational analyses indicated that QWB scores were significantly related to ratings of performance status and that children who had experienced more surgeries and hospitalizations were assessed as more impaired on the QWB. The child's age, toxicity of treatment experience to date, and laboratory values were not significantly related to QWB findings. The potential utility of the QWB as a component of quality-of-life assessment is discussed. PMID- 8500456 TI - Study of pH-dependent structural transition in telomeric sequences by two dimensional gel electrophoresis. AB - We have applied the method of two-dimensional gel electrophoresis to study a pH dependent structural transition in plasmid carrying the Tetrahymena telomeric sequence, (G4T2)n. A study of the two-dimensional patterns makes it possible to obtain energetic characteristics of the transition. We have obtained the nucleation energy of the structure. It proved to be two times lower than the nucleation energy of H-DNA determined before for a d(AG)n insert. The finding partly explains the formation of an eclectic structure in telomeric sequences. We also studied the effect of Zn++ ions on the two-dimensional patterns of gel electrophoresis. Our data show that Zn++ ions can significantly affect the transitions themselves. This finding leads to reinterpretation of numerous data on probing of structural transitions in DNA by the S1 nuclease. PMID- 8500457 TI - Pulsed field agarose gel electrophoresis in the study of morphogenesis: packaging of double-stranded DNA in the capsids of bacteriophages. AB - To understand how comparatively simple macromolecular components become biological systems, studies are made of the morphogenesis of bacteriophages. Pulsed field agarose gel electrophoresis (PFGE) has contributed to these studies by: (i) improving the length resolution of both mature, linear, double-stranded bacteriophage DNAs and the concatemers formed both in vivo and in vitro by the end-to-end joining of these mature bacteriophage DNAs, (ii) improving the resolution of circular conformers of bacteriophage DNAs, (iii) improving the resolution of linear single-stranded bacteriophage DNAs, (iv) providing a comparatively simple technique for analyzing protein-DNA complexes, and (v) providing a solid-phase quantitative assay for all forms of bacteriophage DNA; solid-phase assays are both less complex and more efficient than liquid-phase assays such as rate zonal centrifugation. Conversely, studies of bacteriophages have contributed to PFGE the DNA standards used for determining the length of nonbacteriophage DNAs. Among the solid-phase assays based on PFGE is an assay for excluded volume effects. PMID- 8500458 TI - Pulsed-field polyacrylamide gel electrophoresis: basic phenomena and applications. AB - Pulsed-field gel electrophoresis (PFGE) using polyacrylamide gels, termed pulsed field polyacrylamide gel electrophoresis (PF-PAGE), had been developed for the effective separation of linear DNAs from circular ones [1]. The first generation PF-PAGE employed horizontal polyacrylamide gels run in a contour-clamped homogeneous electric field (CHEF) apparatus. The second generation system, using a vertical slab gel in a discontinuous buffer system and field inversion gel electrophoresis (FIGE), was found to be easier to handle and requires a much shorter time for separation than the previous one [2]. In this report, basic aspects of the second generation PF-PAGE, such as the effects of a discontinuous buffer system and field inversion on the DNA migration in polyacrylamide gels, were investigated. The results indicate that the periodic inversion of electric field can broaden the resolving capability of polyacrylamide gels, enabling DNAs that otherwise fail to enter polyacrylamide gels to be resolved in such systems. Successful and possible applications of PF-PAGE techniques are also discussed. PMID- 8500459 TI - The 0.7 to 3.3 megabase chromosomes from Candida, Kluyveromyces, and Pichia provide accurate size standards for pulsed field gel electrophoresis. AB - Pulsed field gel electrophoresis was used to size intact chromosomal DNAs from Candida albicans, Kluyveromyces lactis, Pichia scolyti, and Pichia mississippiensis by optimization methods using, as size standards, concatenated bacteriophage lambda DNA, and intact and NotI digestion products of Schizosaccharomyces pombe chromosomal DNAs. These newly sized fungal DNAs can now serve as convenient and accurate size standards for DNA molecules between 0.7 and 3.3 megabases (Mb). These size standards are valid over a wide range of different electrophoretic conditions. PMID- 8500460 TI - Two-dimensional motion of DNA bands during 120 degrees pulsed-field gel electrophoresis. AB - The position and velocity of a band of double-stranded, linear DNA from bacteriophage G were measured during 120 degrees pulsed-field gel electrophoresis, using a video micrometer. Both the x and y coordinates were determined simultaneously in the plane of a 1% agarose gel; x is the mean drift direction. For pulse durations T greater than the tube renewal time T*, the path traced by the band of 670 kb DNA in the xy plane was in remarkably good accord with that predicted by Southern's ratchet model. However, the measured instantaneous velocity vx showed a sharp backward spike each time the field changed direction, with amplitude about twice the mean drift velocity. This spike is not consistent with models which assume a constant curvilinear velocity of DNA in a tube, nor with the biased reptation model without fluctuations. The corresponding measurements of vy showed a sharp positive spike with amplitude more than 3 times the plateau velocity in the y direction; neither model predicted this. The sharp velocity spikes are consistent with the idea that, for T > T*, a large fraction of the DNA chains are stretched into U-shaped or herniated configurations. When the field changes direction, the arms of the U's and the hernias recoil rapidly in response to intramolecular DNA chain tension. Because the base of a U or hernia is fixed by gel fibers, the center of mass of the chain recoils backward every time the field changes direction. PMID- 8500461 TI - Effect of one-dimensional pulsed-field gel electrophoresis on linear and circular DNA. AB - A summary of the three main one-dimensional pulsed-field strategies (zero integrated field, forward-biased field, and high frequency modulation) used for separating DNA molecules without band inversion within a preselected size range is given. Each of these strategies has size-specific features which make separations up to 6 Mbp possible. We applied the same methodology to circular DNAs varying in size from 2 kbp to about 4 Mbp. The migration of intermediate sized circular plasmids (50 kbp-400 kbp) under these pulse conditions remains unexplained. On the other hand, preliminary results show that the migration of very large molecules, which are expected to be circular, comigrate with linear chromosomes of the same size under certain pulse conditions. We hypothesize that sample preparation, or the effect of the pulsed field, can create breakage and linearize very large circular DNAs, or that very large circular DNAs (> 2 Mbp) act like linear DNAs of the same size when submitted to one-dimensional pulsed field gel electrophoresis conditions. The most likely possibility is that some of the circular DNAs have been linearized with one break during sample preparation, giving rise to a band at about 4 Mbp. The circular DNAs with more than one break may form an indistinguishable smear. PMID- 8500462 TI - Biased sinusoidal field gel electrophoresis for the separation of large DNA. AB - In agarose gel electrophoresis, in a steady, continuous field, it is well known that the mobility mu, versus size M relation for linear DNAs (L-DNAs) can be divided into three regimes: Ogston regime I for small DNAs, where M dependence of mu, is weak; entangled but unstretched regime II for intermediate-size L-DNAs (of M < 20 kbp), where mu, sigma M-1 so that efficient fractionation is possible; and entangled and stretched regime III for large L-DNAs, where M dependence of mu s is again weak. Although mu s and the regimen boundaries can be altered by adjusting the gel concentration Cgel and/or the field strength E, the features of the M dependence of mu s are essentially unchanged. As to the effect of DNA topology on mu s, we found that in dilute gels (Cgel < 1.0 wt%) coiled, circular DNAs (C-DNAs) of 2-7 kbp size migrate faster than L-DNAs of comparable size, while in concentrated gels (Cgel > 1.5 wt%) C-DNAs migrate much slower than L DNAs. To facilitate separation of large DNAs in the regime III range, we proposed biased sinusoidal field gel electrophoresis (BSFGE), which utilizes a sinusoidal field of strength Es and frequency f superposed on a steady bias field of strength Eb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500463 TI - DNA electrophoresis in polymer solutions: Ogston sieving, reptation and constraint release. AB - The electrophoresis of long polyelectrolytes is considered theoretically, with special attention to duplex DNA. We first discuss quantitative approaches to determine unambiguously the entanglement properties of polymer solutions. Following an idea proposed by Grossman and Soane, we then assume that the "mesh" size of the solution plays the role of a dynamic "pore size" in order to apply theories for gel electrophoresis. In the framework of the Ogston model, we predict that duplex DNA up to 1 kb or more should be separable in dilute (i.e. nonentangled) solutions of high molecular weight polymers. In an entangled solution, and for DNA larger than the pore size, we use a recently developed fluctuation-reptation model to predict the range of sizes in which separation should be possible as a function of electric field E and pore size zeta b. For zeta b larger than the Kuhn length of DNA, we predict a separation up to a size N*scaling as E-1 zeta b-1. For zeta b smaller than the Kuhn length, two different regimes are expected. For small electric fields (typically of the order of 10 V/cm), N*should be proportional to E-1 zeta b-3/2, whereas for high electric fields such as encountered in capillary electrophoresis, we expect that N*is proportional to E-2/5 zeta b-12/5. These predictions are qualitatively different from earlier ones. Finally, we demonstrate that the finite lifetime of the "pores" in an entangled solution (as opposed to a gel) may lead to a new migration mechanism by constraint release, which is not size-dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500464 TI - Dynamics of DNA under pulsed-field gel electrophoresis as analyzed from birefringence rise and decay. AB - The orientation of DNA induced by electrophoretic transport in agarose gel has been studied by optical birefringence. From its field-free decay, it is clearly demonstrated that the degree of orientation results from two processes: alignment along the electric field (stretching of the end-to-end vector) and elongation of the primitive path in the gel (overstretching). Separation of the two contributions allows the experimental determination of the effective charge per base pair, the gel pore size seen by the reptating molecule, the reptation time, the degree of overstretching and the mean relaxation time of the overstretching. Their field and DNA length dependences compare well with theoretical predictions. Similarly, the time at which overstretching presents an overshoot in the rise of the orientation follows closely the predictions of a model based on the evolution of J-shaped conformations. The recovery of such conformations is studied by a sequence of two pulses with variable delay time. The use of directly measured or extrapolated characteristic times and fields in the design of efficient pulse schemes for pulsed-field gel electrophoresis is emphasized. PMID- 8500465 TI - Cellular automaton simulation of pulsed field gel electrophoresis. AB - We describe simulation techniques well suited to detailed investigation of the microscopic behavior of DNA during electrophoretic separation in the diffusive regime. Long polymers moving diffusively in a medium are simulated using microscopic Monte-Carlo steps. Simulations rely upon a recently introduced two space abstract polymer that enables fine-grained massively parallel simulation. Tests of the two-space polymer dynamics are reviewed. The scaling with polymer length of the size and relaxation time of isolated polymers are shown to agree with universal scaling relations. The relaxation time is found to be significantly faster than the alternative bond-fluctuation method. Simplicity of implementation enables simulation on cellular automaton machines (CAM) including CAM-6, and a prototype of the new CAM-8, as well as other massively parallel architectures. Preliminary simulations of polymers migrating under an external field through a random medium of obstacles in two dimensions are described. Two sequences of simulations are performed, with different obstacle densities corresponding to pore sizes larger and smaller than the polymer radius of gyration. In the dilute medium polymers are characteristically draped on single obstacles. In the denser medium draping across multiple obstacles results in reduced orientation in the field direction. A demonstration of rapid 90 degrees field direction switching results in polymer motion toward the expected intermediate direction. PMID- 8500466 TI - Progress in developing improved programs for pulsed field agarose gel electrophoresis of DNA. AB - Details are described here for using a rotating gel to perform pulsed field agarose gel electrophoresis (PFGE) with programmable control of the following variables: magnitude of the electrical field, polarity of the electrical field, temperature of the gel and position of the rotating disk upon which the agarose gel rests. By use of this procedure for programmable control, modes of PFGE have been explored that have the following characteristics: (i) resolution by DNA length is completely lost for DNA shorter than a critical length that increases as the pulse times increase, and (ii) resolution by DNA length is enhanced for longer DNAs that are shorter than a second critical length. This window of resolution can be moved to the position of the 2-6 Mb chromosomes of Schizosaccharomyces pombe. PMID- 8500467 TI - Influence of the agarose matrix in pulsed-field electrophoresis. AB - Properties of agarose potentially relevant to PFGE (pulsed-field gel electrophoresis) are reviewed, and some new information is presented. Agarose polymers appear to have molecular weights in the range of 100,000 to 200,000 Da, but this is not tightly related to the effective gel strength. Agarose has some residual charge, and hence exhibits electroendosmosis (EEO). It is possible to markedly increase the speed of separation of DNA molecules by using agarose of low EEO, especially in low ionic strength, non-borate buffers. This increase is especially noticeable in the relatively long experiments required for separation of large DNAs. It is also possible to increase the range of separation in a single run by use of step gradients of agarose concentration, which allows visualization of yeast chromosomes and lambda-phage restriction fragments in the same lane. Because of the strong influence of concentration on separation, it may be useful for investigators to control water content and related variables. Our lack of knowledge of the detailed microstructure of gels may be barrier to complete understanding of PFGE. PMID- 8500468 TI - "Flip-flop" orientation of agarose gel fibers in pulsed alternating electric fields. AB - The orientation of the agarose gel matrix in pulsed electric fields has been studied by transient electric birefringence. Two types of agarose with different degrees of charge were studied, in addition to agarose solutions and gels containing beta-carrageenan, a stereoisomer of agarose, and polyacrylamide. Agarose gels exhibit normal orientation behavior when short, high voltage pulses are applied to the gel. The sign of the birefringence is positive and the relaxation times are consistent with the orientation of dangling fiber ends parallel to the electric field. When long, low voltage pulses, of the amplitude and duration used for pulsed field gel electrophoresis, are applied to the gel, completely different orientation effects are observed. The amplitude of the birefringence (i.e., extent of orientation) is much larger than expected from the high field results, and the birefringence decay curves contain multiple components of opposite sign. The relaxation times are consistent with the orientation of long agarose chain bundles or fibers, as well as large three dimensional domains. Chain bundles or fibers of the lengths observed in the agarose gels are also observed in agarose solutions, suggesting that the fibers that are free to orient in the gels had previously formed in the sol phase and are only weakly integrated into the matrix structure. In rapidly reversing low voltage electric fields, the sign of the birefringence of the agarose gels reverses from positive to negative in phase with the reversing electric field. This alternating change in the sign of the birefringence suggests that the agarose fibers "flip-flop" in orientation from parallel to perpendicular every time the electric field reverses its direction. Similar effects are observed for agarose gels with different charge densities. The flip-flop orientation and reorientation of agarose fibers within the matrix in reversing electric fields may decrease the microscopic viscosity of the gel, increasing the mobility of large DNA molecules migrating through the gel during electrophoresis. Polyacrylamide gels do not exhibit an anomalous reversal of the sign of the birefringence in reversing electric fields. Hence, the orienting fibers in these gels do not change their direction of orientation in reversing electric fields. Extensive orientation is observed in beta-carrageenan gels, similar to that observed in agarose gels. However, little orientation occurs in polyacrylamide gels, which are chemically crosslinked.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8500469 TI - Job design and job stress in office workers. AB - A model to look at various job components that affect individual well-being and health was developed drawing from the job design and job stress literature. Briefly stated, the model proposes job control to be a primary causal determinant of the stress outcomes. The effects of perceived demands, job content, and career/future concerns were hypothesized to influence the stress outcomes only to the extent of their influence on job control. This was tested in a population of government office employees in various clerical, professional, and managerial jobs all of which involve the use of computers. Results indicated that job control was not a crucial determinant of the stress outcomes, that job demands and career/future concerns were consistent determinants of the stress outcomes, and that job content, demands, and career/future concerns did not influence the stress outcomes through job control as described by the proposed model. The differentiation of job control levels to define specific relationships with stress outcomes and other job elements was shown to be useful because different levels of job control were associated with different stress outcomes and job elements. PMID- 8500470 TI - Physical workload, perceived exertion, and output of cut wood as related to age in motor-manual cutting. AB - Physical workload, output of cut wood, and perceived exertion were studied among 15 younger (mean age 29 years) and 16 older (mean age 59 years) lumberjacks, using a chainsaw and paid on a piece-rate basis. Oxygen consumption was measured with portable equipment, while heart rate was measured telemetrically. The oxygen consumption for all working phases was 1.8 +/- 0.2 l/min (means +/- SD) (younger) and 1.5 +/- 0.2 l/min (older), which corresponded to 49 +/- 4% and 53 +/- 7% of maximal oxygen consumption estimated in ergometer bicycle exercise test. A negative relationship was found between relative oxygen consumption at work and maximal oxygen consumption (ml/kg/min). Mean heart rates for all working phases were 138 +/- 10 beats/min (younger) and 126 +/- 17 (older). The heart rate differed between the working phases, and was significantly higher for both groups during bunching than during the other operations. The output of cut wood did not differ significantly between the groups. Slight but significantly relationships were found between output of cut wood and maximal oxygen consumption (ml/kg/min) and oxygen consumption (ml/kg/min) during work. Rating of perceived exertion (RPE) and simultaneous heart rate recordings during cycle tests and field studies showed significant correlations between heart rate and RPE values during cycling in both groups. RPE values and heart rate in the field showed a slight correlation (younger) and not at all (older). PMID- 8500471 TI - Separating the endogenous and exogenous components of the circadian rhythm of body temperature during night work using some 'purification' models. AB - Ten nurses have been studied for a period of about ten days during which they had rest days and between two and seven successive night shifts. Rectal temperature and wrist movement were monitored throughout, and the nurses kept an activity log. The process of adjustment to night work was assessed by comparing shifts in body temperature with those in mid-sleep, using the mean of the values during rest days as a control in both cases. When raw temperature data were used, the measured shifts were significantly greater than when the temperature data were first modified or 'purified' by a series of methods that took into account the direct effects upon temperature of sleep and physical activity. The greater the 'purification' of the data--whether by using an activity profile derived from a wrist accelerometer or the subject's own log--the less rapid did adjustment to night work appear to be. We conclude that conventional measurements of the adjustment of the temperature rhythm to night work that make use of raw data over estimate it due to masking effects. We suggest also that the purification methods that we have developed can be used in the field and enable estimates to be made of the size of masking effects caused by sleep and activity, as well as the shift of the endogenous component of the circadian rhythm. PMID- 8500472 TI - A psychophysical approach to determine the frequency and duration of work-rest schedules for manual handling operations. AB - The primary objectives of this study were: (1) to test whether rest allowances could be ascertained using a psychophysical methodology; and (2) to examine the effects of gender and frequency of handling on work-rest schedules. Two experiments were conducted, each experimental session at 4h. A psychophysical methodology was used where the subject was given control of the working and resting durations. The results of the study indicated that: (1) the total working time decreased and the total resting time decreased with an increase in the frequency of handling; (2) high frequency tasks required more frequent rest allowances; (3) for the same manual handling tasks, women needed more frequent and longer allowances than men; (4) experience with the manual handling of material reduced the variability collected from the psychophysical methodology. The application of the psychophysical methodology in industry is discussed. PMID- 8500473 TI - The effects of a pneumatic stool and a one-legged stool on lower limb joint load and muscular activity during sitting and rising. AB - Nine healthy male subjects rose from four different stools. The 'ordinary' stool (K) was set at normal chair height, approximately 50 cm, and the 'low ordinary' stool (O), the one-legged stool (T), and the pneumatically-sprung stool (S) were all approximately 32 cm high. The moments of force in the hip, knee, and ankle joints were calculated with a semidynamic technique using a Kistler force plate and video. EMG in four leg muscles was recorded. The part of bodyweight carried by the different stools when the subjects were sitting was measured, and the subjects estimated the effort of rising, using the Borg scale. The low ordinary stool gave higher knee and hip moments than the ordinary stool. Use of the pneumatic stool reduced the knee and hip moments to a level comparable with that of the ordinary stool. The reduction in moment compared with the one-legged stool (T) and the low ordinary stool (O) was significant, both in the knee (p < 0.005) and the hip (p < 0.001). Rising from the three low stools gave no significant differences in mean maximum muscle activity in any of the muscles investigated. The subjects estimated that the pneumatic stool and the ordinary stool were the easiest to rise from. The part of bodyweight carried by the ordinary stool and the low ordinary stool, both around 80% when sitting, was significantly higher than for the two other stools (p < 0.005). It was concluded that a pneumatic stool can be a useful device to workers who work in low positions and rise frequently. PMID- 8500474 TI - Biomechanical and epidemiological investigation of carpal tunnel syndrome at workplaces with high risk factors. AB - This paper deals with the problem of carpal tunnel syndrome (CTS) through investigations of both biomechanical and epidemiological data on seventeen high risk jobs. Biomechanical data were collected from continuous recording of prehension muscular efforts and wrist angular flexion-extension positions for each hand. In order to characterize both static and dynamic behaviours of signals, nine angle and four force indices were built for each hand. The epidemiological data evaluated the probability to contract the CTS (prevalence) on the dominant hand, the non-dominant hand, and both hands simultaneously. Biomechanical and epidemiological data were evaluated using multiple correspondence factor analysis which may consider heterogeneous variables to clarify non-linear relations in a very large data set. The CTS occurred twice more frequently on the two hands together (average 20%) than on the dominant hand alone. Such a result confirmed the outcome of other studies that non-occupational factors could be more important than occupational factors. The prevalence for both hands was highly correlated with the frequency of flexion and use of high forces. High or low flexions appeared to be a greater risk factor than high or low extensions. PMID- 8500475 TI - Direct observation of driving, self reports of driver behaviour, and accident involvement. AB - Forty-eight drivers answered a set of written questions about their driving style and drove a pre-defined, mixed urban and motorway route under observation. For 20 drivers there was a second observer in the car to check on inter-observer reliability. Relationships were examined between self-reports of driver behaviour and observers' reports, and between both of these and the number of accidents in which the drivers had been involved in the past three years. The results indicated that there was good inter-observer agreement on a number of important variables including speed, calmness, and attentiveness. Inter-observer reliability for other variables was less good; among these were preferred distance to car in front, use of indicators, and aggressiveness. Observers also showed good agreement on overall ratings of driver skill and safety. Observed speed on the motorway correlated well with drivers' self reports of normal driving speed. Observer ratings of calmness correlated significantly with self reports of calmness. Also observer ratings of attentiveness and carefulness correlated significantly with self-reports of deviant driving behaviour. Observed speed on the motorway showed a clear positive correlation with self-reported accident involvement. The results indicate that self-reports of certain aspects of driver behaviour can be used as surrogates for observational measures, thus providing a convenient extension to the researcher's methodological armoury. One such aspect is speed which appears to play an important role in accident involvement. PMID- 8500476 TI - Antibody response to a major human Pneumocystis carinii surface antigen in patients without evidence of immunosuppression and in patients with suspected atypical pneumonia. AB - IgG and IgM antibodies to a purified human Pneumocystis carinii surface antigen (gp95) were measured in 694 serum specimens from two different population groups using an EIA technique. In a population of 441 patients with no evidence of immunosuppression, the percentage of persons positive for IgG antibodies to gp95 was significantly lower in the age group 1 to 9 years (30%, 23/77) compared to persons 10 to 19 years old (56%, 49/88). In the age group 1 to 14 years there was a significant correlation between the percentage of persons with IgG antibodies to gp95 and age. In 106 consecutive patients under evaluation due to atypical pneumonia, 76 patients showed no change in the titre of antibodies to Legionella spp. or Mycoplasma pneumoniae in two consecutive serum samples. Three of these 76 patients (4%) demonstrated an increase in the level of IgG antibodies to gp95 in the paired samples. One of these patients had a verified Pneumocystis carinii pneumonia, and the two others were elderly men in whom no microbiological diagnosis of the pneumonia was established. Thus, it is concluded that IgG antibodies to gp95 develop in the majority of nonimmunosuppressed persons before the age of 13. Furthermore, Pneumocystis carinii pneumonia should be considered in the differential diagnosis in patients suspected of having atypical pneumonia. PMID- 8500477 TI - Pneumonia caused by Nocardia nova and Aspergillus fumigatus after cardiac transplantation. AB - Nocardia nova, a newly established species of the Nocardia asteroides complex, has recently been characterized as a human pathogen. This report of a case of pneumonia caused by Nocardia nova and Aspergillus fumigatus in a patient after cardiac transplantation is the first reported infection caused by Nocardia nova following its detailed description. Accurate identification and susceptibility testing of the Nocardia nova isolate allowed successful oral therapy with clarithromycin when therapy with sulfisoxazole was not tolerated. PMID- 8500478 TI - A cluster of four cases of Mycobacterium haemophilum infection. AB - Four cases of infection with Mycobacterium haemophilum occurred at a single hospital in a seven-month period. Only 22 cases have been reported since 1976. All four patients were immunocompromised; two had AIDS and two were the first known recipients of allogeneic bone marrow transplants (BMT) to develop the infection. One BMT recipient died of Mycobacterium haemophilum pneumonia. The organism requires hemin or ferric ammonium citrate and incubation of media at 30 degrees C for optimum growth. Clinicians and microbiologists should consider infection with Mycobacterium haemophilum, particularly when specimens are from immunocompromised patients with unexplained illness and/or when acid-fast bacilli are seen on smear. PMID- 8500479 TI - Disseminating infection with Scytalidium dimidiatum in a granulocytopenic child. AB - A 13-year-old Moroccan boy in The Netherlands developed fever and a lesion resembling ecthyma gangrenosum on the abdomen during cytostatic drug treatment for a lymphoblastic B-cell lymphoma. Scytalidium dimidiatum was cultured from blood and the abdominal skin lesion. The patient was successfully treated with amphotericin B. The fungus Scytalidium dimidiatum is a fairly common plant pathogen in tropical and subtropical countries and is known to cause dermatomycoses in humans in these areas. This case demonstrates that it is necessary to be aware that immigrants from these areas can import their own fungal flora, some members of which may cause life-threatening disease in the case of patients with immune suppression. PMID- 8500480 TI - Evaluation of two enzyme immunoassays for rapid detection of group B streptococci in pregnant women. AB - The performance of two enzyme immunoassays for rapid detection of group B streptococci (GBS) was evaluated in comparison to culture using cervical swabs from 191 pregnant women. Ten percent of the women harboured GBS. There were two positive results in the Icon assay (Hybritech), both in women with heavy growth in the culture, and four positive results in the Quidel assay (Quidel), two in the women with heavy colonization and one each in women with moderate and light growth of GBS respectively. The sensitivity of both assays was low, being 11% (2/18) for the Icon assay and 24% (4/17) for the Quidel assay. The specificity of both assays was 100%. Both assays could detect > or = 10(6) group B streptococci per swab. A positive result justifies ampicillin prophylaxis due to the high risk for the newborn. A negative result should be confirmed by rapid culture techniques. PMID- 8500481 TI - Identification of Staphylococcus epidermidis and Staphylococcus hominis from blood cultures by testing susceptibility to desferrioxamine. AB - Testing susceptibility to desferrioxamine has recently been described as a method for the identification of Staphylococcus epidermidis. This method was compared to a commercial test and the tube coagulase test for the identification of staphylococci from blood cultures and other fluid specimens. A total of 216 isolates was tested over a 13-month period. Sensitivity of the desferrioxamine test in identifying isolates of Staphylococcus epidermidis and Staphylococcus hominis was 97.3%, while specificity was 91.8%. When isolates displaying discrepant desferrioxamine results were characterized using recently described interpretive criteria, sensitivity and specificity of the desferrioxamine test improved to 100%. The desferrioxamine test was reliable, inexpensive and simple to perform, and should prove useful in the diagnostic laboratory. PMID- 8500482 TI - Marked decrease in susceptibility of Shigella to ampicillin and cotrimoxazole in Israel. PMID- 8500483 TI - Investigation of high negative values obtained with the chlamydiazyme enzyme immunoassay for detection of Chlamydia trachomatis. PMID- 8500484 TI - Evaluation of a latex agglutination test in the diagnosis of rubella infection. PMID- 8500485 TI - Cross-reaction of spontaneous capsule-deficient Haemophilus influenzae type b mutants with type-specific antisera. PMID- 8500486 TI - Incidence of hospital-acquired infection and length of hospital stay. AB - Two different measures of hospital-acquired infection (HAI), risk per discharge and incidence rate, were used to analyse the incidence of 225 primary HAIs detected in 3,090 patients in an 11-month survey. Longer hospital stay was associated with a greater risk of developing HAI, but the strength of the association was different for the two measures used. Day-specific incidence rates were found to vary, with a peak between the 14th and 19th days of hospitalisation. Similar patterns were observed when the data were stratified by age, sex and operation. Methods for calculating HAI should control for the length of hospital stay. Further studies are required to clarify the mechanisms that affect the temporal pattern of incidence of HAI observed with length of hospitalisation. PMID- 8500487 TI - Serological response to coagulase-negative staphylococci in patients with peritonitis on continuous ambulatory peritoneal dialysis. AB - Sera and dialysis effluent from 20 patients on continuous ambulatory peritoneal dialysis (CAPD) with coagulase-negative staphylococcal (CNS) peritonitis were examined by immunoblotting for antibody activity against CNS. Immunoblotting was highly sensitive and demonstrated significantly greater antibody activity in serum and dialysate of infected patients compared with that of uninfected CAPD patients or healthy volunteers. Fourteen of 20 infected CAPD patients had strong antibody activity (> 7 bands); one patient had equivocal activity. Five patients had weak antibody activity, two of whom suffered from recurrent peritonitis with distinguishable CNS strains despite a satisfactory CAPD technique. One patient with a poor CAPD technique had strong antibody activity, but suffered from recurrent peritonitis. Examination of sequential sera suggested that seroconversion occurred soon after insertion of the Tenckhoff catheter, possibly in the absence of clinical infection. Antibody activity against a 25 kDa staphylococcal protein was significantly associated with peritonitis. PMID- 8500488 TI - Frequency of enterovirulent Escherichia coli in diarrhoeal disease in The Netherlands. AB - To assess the role of enterovirulent Escherichia coli in The Netherlands, faecal samples of 279 patients (108 children, 171 adults) with diarrhoea and 100 healthy controls were investigated in a prospective study. Enterovirulent Escherichia coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enteropathogenic Escherichia coli (EPEC), verocytotoxin producing Escherichia coli (VTEC) and enterotoxigenic Escherichia coli (ETEC). The rate of isolation of EPEC was 6.5% in patients with diarrhoea and 2.0% in asymptomatic persons. During the study period, no VTEC were isolated from patients with diarrhoea. ETEC were isolated from two persons, both of whom had experienced diarrhoea and had returned from travel in (sub)tropical areas. Our results suggest that diarrhoea is sporadically caused by ETEC among the indigenous population of The Netherlands, and is mainly associated with travel in endemic areas. Furthermore, the presence of EPEC probe-positive strains in the stool need not always be accompanied by symptoms of diarrhoea. PMID- 8500489 TI - Cell-associated haemolytic activity of Helicobacter pylori. AB - Helicobacter pylori cells cultured on solid medium were quantitatively tested for haemolytic activity against erythrocytes of man, sheep, the guinea pig and rabbit. Using 4-day and 8-day cultures of two standard strains (ATCC 43504, IMMi 676), human erythrocytes were not lysed by 10% bacterial suspensions. Rabbit erythrocytes were the most sensitive to 8-day cultures. Hot-cold incubation yielded the highest haemolysis titres. The extent of haemolysis strongly correlated with the number of bacterial cells. Supplementation of the test medium (PBS, pH 7.4) with L-cysteine, dithiothreitol, MgCl2, EDTA, cholesterol, lecithin or sphingomyelin did not influence the haemolysis titres. They were significantly reduced in the presence of pronase E, human serum, bovine serum albumin or CaCl2, and by heat treatment of the bacteria. Supplementation of the test medium with cardiolipin strongly increased the haemolysis titres. Comparing the cell associated haemolytic activity of 18 strains, the titres ranged from < 2 to 64, with a median titre of 16. No correlation was found between the haemolytic activity and phospholipase C activity of the cell suspensions. It was concluded that the formation of lysophosphatides and non-enzymatic factors rather than a sulphydryl-activated cytolysin or phospholipase C are responsible for the cell associated haemolytic activity. This property may be involved in the pathogenicity and virulence of Helicobacter pylori. PMID- 8500490 TI - Histopathological characterization in carcinoma of the endometrium. Comparison between biopsy and pathological examination of specimen. AB - On the basis of a case series of 577 patients affected by carcinoma of the endometrium treated during the period 1963-1989 in the Gynecologic Institute of the Padua University, the present work examines the reliability of endometrial biopsy aiming at the correct histopathologic diagnosis, through comparison with the subsequent histologic examination of the surgical specimen. It is shown how simple biopsy alone allows for correct diagnosis of histotype in 91.6% of cases of adenocarcinoma, while the reliability of such an examination is reduced, respectively, to 30.7% in adenoacanthoma and to 37.5% in adenosquamous histotypes. PMID- 8500491 TI - Syndrome of primary multiple endometrial, breast, ovarian and colon adenocarcinoma. AB - Incidence, manifestation time and treatment results were studied in 356 patients with synchronous and metachronous primary multiple tumours, who made 4.4% of 8065 primary patients with endometrial (1400), breast (5450) and ovarian (1215) cancer. 244 of 356 polyneoplasia patients (68.5%) had adenocarcinoma of the mentioned sites colon. Risk factors for the appearance of polyneoplasia were established. After the radical treatment, polyneoplasia prognosis was not generally worse than that of solitary tumours. PMID- 8500492 TI - Relative risk of development and active detection of primary multiple endometrial, breast and ovarian cancer. AB - The cumulative relative risk of polyneoplasia and the factors which influence it were retrospectively studied in 8065 primary patients (1400 endometrial cancer, 5450 breast cancer, 1215 ovarian cancer). In breast cancer the cumulative risk of patients developing synchronous corpus uteri cancer is 13.9 times higher than in the general population. In corpus uteri cancer patients risk of breast cancer 9.0. The indices mentioned increase from the age of 40-59 years and in the first stage. In prospective research mammography and ultrasonic examination of the pelvis were carried out in 481 patients of primary corpus uteri cancer. Asymptomatic initial patients of primary corpus uteri cancer. Asymptomatic initial breast cancer of the first stage was detected in 1.9%, 19 times more frequently than in the controls (24.29 practically healthy women). Among 318 primary breast cancer patients cytologic examination of endometrial material allowed us to detect endometrial cancer in 2.4% (6 times more frequent than in the controls), and under echography ovarian cancer of the 1.st-2.rd stages was diagnosed in 1.3%. PMID- 8500493 TI - The role of the endocrine factors and obesity in hormone-dependent gynecological neoplasias. AB - Between September 1990 and February 1992, we studied 70 women of post-menopausal age, of whom 33 were affected by hormone-dependent gynecologic tumors and 37 by other pathologies, measuring estrogens, androgens, SHBG and also measuring excess fat and its distribution. The aim of our research was to ascertain what relation there was between adipose tissue, taking account central or peripheric localization, the levels of sex steroids and the onset of endometrial and breast cancer. In the group of tumor patients, we found a quantity of fat mass greater than in the control group (p < 0.05); there was, beside, in the first group, an inverse proportional correlation between the SHBG levels and BMI, and between SHBG and the fat mass (P < 0.05). We also observed an inverse relation between the levels of testosterone and SHBG (P < 0.05). These findings confirm the role that the adipose tissue and androgens would have on the globulin production, which in turn would reflect on the percentage of potentially active steroids in endometrial and mammary tissues. We also wished to ascertain if the distribution of fatty tissue (prevalently abdominal or prevalently gluteo-femoral) could have different endocrine-metabolic consequences. We found a directly proportional relation between an index of central obesity, the T/L Ratio, and the levels of DHA-S (P < 0.05), but the significance of this relation is not clear, inasmuch as DHA-S is one of the least active of the androgens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500494 TI - Hyperinsulinemia as a factor modifying sensitivity of endometrial carcinoma to hormonal influences. AB - In 22 patients with endometrial carcinoma, Stage I-III (mean age 57.8 years) with obesity, initial and reactive hyperinsulinemia (during glucose load) was revealed. Significant correlations between values of "peak" and field-square of the insulin secretion curve and cytoplasmatic receptors to Estradiol and Progesterone in the tumor were found. In a group of the patients with high values of reactive hyperinsulinemia significantly larger amounts of steroid hormone receptors in the tumor were determined as compared to the group of the patients who had low insulinemia values. On considering these data a possible conclusion was reached as to the modifying influence of hyperinsulinemia on sensitivity of endometrial carcinoma to hormone receptor synthesis in the tumor by insulin. PMID- 8500495 TI - The role of insulin and renin in the pathogenesis of hormone-dependent neoplasias. a). Insulin. AB - Weight increase is frequently observed in women of menopausal age and the androgens secreted at the ovarian level are converted into estrogens at adipose tissue level, because of the presence of specific enzymes, the aromatases. Insulin and the androgens reduce the synthesis of Sex Hormone Binding Globulin (SHBG) at the hepatic level, thus increasing the amount of free steroids able to act at the level of the hormone-dependent tissues. Besides, the insulin stimulates androgenic synthesis at the level of the ovarian stroma in postmenopausal women. In this research, we studied 83 postmenopausal women, 41 with hormone-dependent pathologies and 42 affected by other pathologies, and we observed that women affected by breast and endometrial neoplasias presented a reduced tolerance to glucose, a higher level of circulating androgens, a large quantity of fatty tissue and a SHBG concentration inversely proportional to insulin level. These results suggest that the ovarian synthesis of androgens increase in women in postmenopausal age affected by hormone-dependent pathologies, and that insulin may play a part in the pathogenesis of such neoplasias. PMID- 8500496 TI - The role of insulin and renin in the pathogenesis of hormone-dependent neoplasias. b). Renin. AB - Recently, a prorenin-renin-angiotensin system which could be correlated to the reproductive function, although independent from the renal renin-angiotensin complex, has been observed also at ovarian level. It had been supposed that the renin itself by influencing the metabolism of steroid hormones is responsible for the pathogenesis of hormone-dependent neoplasias, endometrial and breast carcinoma. This would lead to the consideration of hypertension as a primary risk factor for such pathologies and not only as secondary to obesity. This research has not, however, revealed significant relations between the plasmatic concentration of renin and the hormone variation responsible for the pathogenesis of hormone-dependent neoplasias. PMID- 8500497 TI - Criteria of endometrial carcinoma sensitivity to hormone therapy: pathogenetic type of the disease and the tumor reaction to tamoxifen. AB - The results of assay of receptorial status of tumor in 152 primary patients with endometrial carcinoma are presented. It was shown that a 10-day course of preoperative Tamoxifen therapy (course dose 0.6 g) was able to increase significantly concentrations of nuclear estradiol receptors and cytoplasmatic progesterone receptors in the tumor. This phenomenon followed morphological changes in the tumor and was established in both hormone dependent type (72.7%) and hormone independent type of endometrial carcinoma (45.5%). The assay of the dynamics of receptorial status of primary endometrial carcinoma under influence of Tamoxifen before surgery might be an informative test for selection of sensitive patients with poor prognosis for prolonged hormone therapy in remission to prevent development of recurrencies. PMID- 8500498 TI - Morphological aspects of the hormone-induced pathomorphosis of endometrial carcinoma. AB - The paper presents the results of treatment of 488 patients with primary endometrial carcinoma. All patients received adjuvant hormonotherapy (oxyprogesterone caproate, and some patients previously oestrogens) in combination with surgery and postoperative irradiation. The study of tumor morphology on ultrastructural level and by histochemical methods provided additionally useful findings. Depending on the degree of changes in the tumor structure after hormone therapy it appeared possible to distinguish the following varieties of results: 1) Complete regression of tumor. 2) An increase in structural and functional differentiation as compared with the initial level differentiation of tumor. 3) Absence or doubtful effect. In the paper the working classification of malignant adrenogenic tumors of the uterus is presented. PMID- 8500499 TI - Favourable influence of adjuvant hormone therapy by oxyprogesterone caproate (OPC) and by its combination with tamoxifen on 5-year survival rate of surgical and combined treatment of primary endometrial carcinoma patients. AB - In a prospective and randomized study comprising 540 primary endometrial carcinoma patients the influence of adjuvant hormone therapy by Oxyprogesterone caproate (OPC) and by its combination with Tamoxifen on the corrected survival rates after surgical and combined (surgical and irradiation) therapy was investigated. As was shown OPC administered preoperatively and after surgical and combined therapy from 6 up to 36 months increased the corrected survival rates as compared with that in patients who did not receive hormone treatment. Combination of OPC and Tamoxifen administered additionally to surgical and combined therapy increase the corrected survival rate at the 5th year by 19%. One can conclude that adjuvant hormone therapy in endometrial carcinoma patients who have unfavourable prognosis of the disease must be administered for not less than 3 years in order to obtain prolongation of remission of the disease. PMID- 8500500 TI - Optimal variants of treatment of stage I endometrial carcinoma and its choice. AB - 2195 patients affected by endometrial carcinoma were treated at the Tbilisi and the St. Petersburg Oncological Institutes from 1968 to 1987. The incidence of different stages was respectively: I 78.8%; II 11.6%; III 9.0%; IV 0.4%. Adenocarcinoma was the histotype more frequently observed and the grade of differentiation was respectively: G1 39.3%; G2 51.3%; G3 9.4%. The incidence of lymphnodal invasion was equal to 6.2% in I Stage, 12.2% in II Stage and 37.8% in III Stage. In Stage I surgery was the treatment of choice in all cases and in the 70.5% of cases additional treatments were added: in G1, G2 grade endometrial cancer additional hormone therapy, remote irradiation and postoperative hormone therapy were used, whereas in G3 tumours intracavitary irradiation was frequently added in the St. Petersburg Institute. The 5 year survival rate of patients at Stage I was equal to 70.9% in retrospective analysis (1968-1982) and 84.6% in patients followed prospectively (1983-1987). PMID- 8500501 TI - Endometrial cancer treatment today. AB - The Authors stress the role of surgery in the clinical management of endometrial cancer. The half Century case-series of Padua Gynaecologic Institute is considered. PMID- 8500502 TI - Geographic peculiarities of endometrial and cervical cancer incidence in five continents (review). AB - The review of references and data on endometrial and cervical cancer incidence in five continents (1970, 1976, 1982, 1987) are presented. The increase in cervical cancer rates in the developing countries of Asia, Africa and Latin America has been recorded. The hormonedependent tumours (endometrial, breast cancer) prevail in the economically developed countries of Europe and North America. They have shown a tendency to increase since the end of the 70's. The possible causes of peculiarities in oncogynecological incidence have been discussed. PMID- 8500503 TI - Selective screening of hormonodependent tumours in women's reproductive system organs. AB - The study is devoted to research of the selective screening possibilities for revealing of hormonodependent tumours of the reproductive system organs in women (endometrial carcinoma, ovarian and breast cancer). The detection of risk factors of cervix uteri cancer, endometrial carcinoma, ovarian and breast cancer has been carried out with the help of a case-control study (311 patients with cancer and 14,872 controls). On the basis of the established risk factors by means of mathematical methods the optimized calculation programmes of individual risks and models in the formation of risk groups of hormonodependent tumours (control 0.32%) have been detected. Through this approach the practical significance of hormonedependent tumours of the selective screening of the reproductive system organs in women has been augmented. PMID- 8500504 TI - Endometrial cytology for the prevention and early diagnosis of endometrial neoplasias. AB - One hundred and forty women, aged between 46 and 70 years, were submitted to periodic colpocytologic, colposcopic and cytologic endometrial checking. None of the patients had been treated by estrogenic therapy. We evaluated the possible morphologic modifications of the endometrium over time by periodic cytologic checks, personalized on the basis of the anamnestic and actual risks of the patients. From the data it was noted that the endometrium in pre- and in post menopause may present changes in the absence of substitutive therapies. In fact in women in post-menopause we found 33% of atrophic endometria at first check, going down to 22.3% at the second, while the incidence of hyperplasia increased slightly. At the second check we always diagnosed 2 cases (2.6%) presenting atypia, confirmed by subsequent curettage. At the third check an increase was observed of atrophic endometria (41.8%) and a reduction of focal hyperplasia (4%). Among women in pre-menopause there was a high incidence of endometria with focal hyperplasia, 37.5% at the first check, 40.6% at the second and 39.6% at the third; hyperplasia in 11.5% of cases at first check, 12.5% at the second and 6.3% at the third; presence of atypia in 1.5% of cases at the second check and 3.2% at the third. Curettages subsequently confirmed diagnosis in these last three patients. In the cases where small fragments of endometrial tissue appeared in the cytological sample we found good agreement between histologic and cytologic diagnoses; the latter slightly overestimated focal hyperplasia and diffuse hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500505 TI - Oxygen radicals induce pulmonary vasoconstriction in pigs without activating plasma proteolytic cascade systems. AB - The effects of infusion of the oxygen radical generating system, hypoxanthine xanthine oxidase, on pulmonary hemodynamics and plasma proteolytic systems, as the plasma kallikrein-kinin and fibrinolytic systems, were studied in pigs by infusion of xanthine oxidase into the pulmonary circulation. A marked pulmonary vasoconstriction and increase in vasculature resistance with a maximum after 25 min was observed. The effects were attenuated by indomethacin, allopurinol and catalase. During the 130-min observation time there were no signs indicating activation of either the plasma kallikrein or the plasma fibrinolytic systems. PMID- 8500506 TI - Is there a pericardial restriction to the cardiac secretion of atrial natriuretic factor? AB - Atrial natriuretic factor (ANF) is secreted from atrial myocytes in response to increased atrial wall stress caused by increased transmural pressure. This study investigates whether the presence of an intact pericardium restricts the ANF secretory response to an increment in left atrial pressure caused by acute aortic constriction in anaesthetized open-chest pigs. The rise in ANF plasma concentration secondary to constriction was higher when the pericardium had been surgically opened than when it was left intact. Furthermore, an opened pericardium led to a larger increase during constriction in left atrial diameter as measured by sonomicrometry. The results suggest that the intact pericardium restricts the cardiac release of ANF secondary to aortic constriction, probably by restricting left atrial dilatation. PMID- 8500507 TI - Influence of biosynthetic human growth hormone on the biomechanical strength development in skin incisional wounds of diabetic rats. AB - The influence of biosynthetic human growth hormone (b-hGH) on the mechanical strength development of skin incisional wounds in diabetic rats has been investigated after 4, 7 and 21 days of healing. Diabetes caused decreased mechanical strength of the wounds. After 21 days of healing, the diabetic animals treated with b-hGH from 7 days before wound infliction had an increased maximum load (14%) compared with the untreated diabetic animals. After 4 and 7 days of healing, no differences in the biomechanical strength of diabetic wounds with and without b-hGH treatment were found. The diabetic animals receiving b-hGH showed a significant increase in body weight compared with the untreated diabetic animals. In the diabetic animals, the blood glucose concentration was increased by treatment with b-hGH. In conclusion, treatment with b-hGH from 7 days before operation can counteract the reduced mechanical strength of skin wounds in diabetic rats on day 21. PMID- 8500508 TI - Liver regeneration following 68% partial orthotopic liver transplantation in the rat. AB - Liver regeneration following transplantation in 'small for size' conditions is not fully understood. We therefore evaluated the regenerative response of transplanted partial liver grafts in outbred rats without the use of immunosuppression and compared it to liver regeneration following resection. The transplanted livers showed enhanced regeneration compared to controls. We suggest that this is caused by activation of the immune system. PMID- 8500509 TI - Preservation of small bowel grafts--a comparison with two standard solutions. AB - This study investigates the use of EuroCollins (EC) and University of Wisconsin (UW) solution, two major preservation fluids, for small bowel preservation. After in situ flushing, grafts were cold-stored at 4 degrees C with either EC for 30 min (group 1a), 6 h (group 1b) and 12 h (group 1c) or with UW for 30 min (group 2a), 6 h (group 2b) and 12 h (group 2c). Using UW, cold ischemia was extended to up to 18 h (group 2d). As a control, small intestines were flushed and stored for the same time periods in cold saline (group 3a-c). Survival in group 1b was 66% versus 100% in group 2b. After 12 h 80% survived in group 2c, but there were not survivors in group 1c. After 18 h of cold storage, survival was only observed in group 2d (25%). Saline was ineffective after 6 h of preservation. Histology at the end of preservation revealed characteristic changes for EC (intracellular vacuoles) and UW (amorphic granules). We conclude that with UW small bowel can be preserved for up to 12 h. PMID- 8500510 TI - Histopathologic and flow cytometric analysis of colorectal polyps resected at endoscopy. AB - Forty-seven colorectal polyps of various histologic types were studied using retrospective flow cytometric (FCM) DNA analysis to determine the prevalence of aneuploid cell populations and whether they were associated with any particular histologic features. Overall, 6 of 47 polyps (12.8%) contained DNA aneuploid cells, comprising 4 adenomatous polyps, 1 of 12 with mild atypia (8.3%), 2 of 19 with moderate atypia (10.5%) and 1 of 4 with severe atypia (25.0%), and 2 of 4 polyps (50.0%) with histologic features of carcinoma in situ (CIS). The incidence of DNA aneuploid cells in CIS was significantly higher than that of all adenomatous polyps (p = 0.043). All of the 8 hyperplastic polyps were diploid. The detection of aneuploidy as a marker of increased risk for malignant transformation was possible even in colorectal adenomas measuring < or = 10 mm. These results show that retrospective FCM analysis can detect DNA aneuploidy in adenomatous polyps and that DNA aneuploidy may occur before histologic evidence of invasive carcinoma. PMID- 8500511 TI - Adipose tissue and muscle volume determination by computed tomography in acromegaly, before and 1 year after adenomectomy. AB - The adipose tissue volume, skeletal muscle and skin volume and visceral organ volume were determined using the multiscan CT (computed tomography) technique in 15 patients with acromegaly. The examinations were performed before treatment and 1 year after transsphenoidal adenectomy. The mean body weight did not change significantly after treatment; 91.3 kg and 92.3 kg pre and postoperatively in men and 66.7 kg and 65.9 kg in women respectively. The total adipose tissue volume increased by 7.11 (59.2%, P < 0.01) in the male group and 3.9 1 (20.3%, P < 0.05) in the female group. Muscle and skin mass and visceral organ mass decreased significantly after treatment. The muscle and skin mass decreased by 3.6 1 ( 7.4%, P < 0.01) in males and by 3.2 1 in females (-11.5%, P < 0.02). The corresponding decrease in visceral organ mass was 1.5 1 (-17.0%, P < 0.01) in males and 1.0 1 (15.4%, P < 0.05) in females respectively. On average, the fractions of adipose tissue in the subcutaneous trunk and the intra-abdominal depots increased after treatment, while the fractions of adipose tissue in the limbs and the head and neck region decreased. The change in adipose tissue distribution pattern reached significance (P < 0.005) in men only. PMID- 8500512 TI - Effects of acute respiratory acidosis on water and electrolyte transport in the human ileum. AB - Animal experiments have shown that acute respiratory acidosis stimulates water, Na and Cl absorption and HCO3 secretion in the ileum. The aim of this study was to investigate whether the human ileum also responds to changes in systemic acid base balance. Seven healthy volunteers (mean age 24, range 21-29 years) underwent segmental ileal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. A 30 cm test segment was perfused under steady state conditions with a plasma-like electrolyte solution containing PEG as a non absorbable volume marker. After a control period, respiratory acidosis (blood pCO2 56.2 mmHg, pH 7.29 and [HCO3] 26.4 mmol l-1) was induced by CO2-breathing over a period of 50 min. Acute respiratory acidosis stimulated net HCO3 secretion in patients secreting HCO3 and reduced absorption in patients exhibiting net HCO3 absorption. These changes were immediate and appeared to be at least partly reversible. Net water, Na, K and Cl movement were not affected. The data suggest that HCO3 transport in the human ileum responds to acute respiratory acidosis. PMID- 8500513 TI - Lipid synthesis and apolipoprotein gene expression in hepatocytes in primary culture from (puromycin-induced) nephrotic rats. AB - Primary culture of hepatocytes from puromycin aminonucleoside-induced nephrotic rats were used to discriminate between the hepatic and extra-hepatic contribution to the hyperlipidemia occurring in the nephrotic syndrome. De novo lipogenesis and utilization of exogenous fatty acids were not modified in nephrotic hepatocytes as compared to controls. In contrast 2.2 and 5.3-fold more triacylglycerol and phospholipids were secreted respectively by nephrotic hepatocytes than by controls. Triacylglycerol overproduction was not associated with an increase either in apo B mRNA level or in apo B synthesis or secretion measured by [35S]-methionine incorporation and immunoprecipitation. We also observed a significant increase in apo AI and apo E synthesis and secretion by nephrotic hepatocytes. This increase was correlated with a greater amount of apo AI and apo E mRNA than in controls. The overproduction of apo AI and apo E by nephrotic hepatocytes might intervene in the clearance of plasma lipoproteins and the redistribution of plasma cholesterol. PMID- 8500514 TI - Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females. AB - Obesity is associated with dyslipidaemia and increased morbidity and mortality from premature atherosclerosis and diabetes mellitus. Particularly, hypertriglyceridaemia is a characteristic finding in patients with obesity. In addition, the elevated levels of triglycerides may be an important risk factor for development of the obesity-related complications. Lipoprotein lipase activity in skeletal muscle tissue (mLPL) has previously been found to be an important factor regulating the concentration of serum triglycerides. To describe the relationship between mLPL, triglycerides and fatness/fat distribution in more detail we have investigated these parameters under basal conditions and during insulin stimulation in 20 obese females. During hyperinsulinaemia (204 microU ml 1) for 4 h the mLPL activity decreased from 528 +/- 52 nmol FFA g-1 to 412 +/- 44 (P < 0.001). Basal mLPL was negatively correlated with serum triglycerides (r = 0.48, P < 0.05) and positively correlated with HDL-cholesterol (r = 0.58, P < 0.01). Employing multiple variance analysis it was found that both BMI and WHR were negatively correlated to mLPL, however, the impaired lipid profile (high triglyceride, low HDL-cholesterol, high FFA) could only be related to BMI and not to WHR in these obese females. However, reduced insulin-action (insulin resistance) was closely related to abdominal fatness determined by WHR both in relation to the insulin-effect on mLPL as well as for the insulin-effect on whole body glucose metabolism (clamp-study).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500515 TI - A comparison of three diuretic regimens in heart failure. AB - Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment 1) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 (P < 0.02) and 6.7% lower during treatment 3 (P < 0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P < 0.05) and 18% lower during treatment 3 (P < 0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand. PMID- 8500516 TI - Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration. AB - HMG-CoA reductase inhibitors effectively reduce the concentration of low density lipoproteins (LDL) in plasma. Lipoprotein(a) [Lp(a)] may be as atherogenic as LDL. A few studies, only one of which was placebo controlled, suggest that the HMG CoA reductase inhibitors either do not affect Lp(a) or they increase Lp(a). The response of Lp(a) to HMG-CoA reductase inhibition has not been related to apolipoprotein(a) phenotypes in previous studies. We conducted a double-blind, placebo controlled study of pravastatin in 51 patients with familial hypercholesterolemia (FH) (n = 43) or probable FH (n = 8). All patients had LDL cholesterol concentration above 4.1 mmol l-1 despite treatment with diet and bile acid sequestration. In patients assigned to pravastatin (n = 34), the mean concentrations of total cholesterol and LDL cholesterol fell significantly (P < 0.01) when compared to placebo. Lp(a) increased (P < 0.01) from a mean (+/- SD) of 33.6 +/- 40.8 mg dl-1 to 41.1 +/- 46.1 mg dl-1 on pravastatin but was unchanged during placebo treatment. The percentage increase in Lp(a) was the same in patients with different apo(a) phenotypes, and hence the absolute increase in Lp(a) was greatest in patients with the low molecular weight apo(a) phenotypes. PMID- 8500517 TI - Abnormalities in left ventricular diastolic function in male patients with rheumatoid arthritis without clinically evident cardiovascular disease. AB - Epidemiological studies have suggested that patients with rheumatoid arthritis (RA) have increased mortality due to cardiovascular disease. We studied cardiac performance in 12 asymptomatic male patients with RA and 14 control subjects to elucidate early disturbances in cardiac function. In echocardiography, isovolumic relaxation time was longer (64 +/- 6 vs. 49 +/- 3 ms, mean +/- SEM, P = 0.010) and peak filling rate (134 +/- 10 vs. 159 +/- 6 mm s-1, P = 0.015) lower in patients with RA than in control subjects, reflecting an impairment in left ventricular diastolic function. Left ventricular systolic function assessed by radionuclide angiocardiography at rest and during exercise was similar in both groups. There were no differences between the patients with RA and control subjects in the heart rate, systolic blood pressure and oxygen uptake during peak exercise. Left ventricular diastolic function is impaired in spite of normal left ventricular systolic function in patients with RA without clinically evident cardiovascular disease and this may contribute to the excess of cardiovascular mortality in patients with RA. PMID- 8500518 TI - Gemfibrozil increases apolipoprotein A-I and cholesterol concentrations in human peripheral lymph. AB - Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18-60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A-I concentration of 30-108% (mean, 66%; P < 0.01), and in lymph cholesterol concentration of 35-100% (mean, 59%; P < 0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A-I concentration (mean, +7%) and plasma total cholesterol concentration (-7%) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood-endothelium interface increases the transfer of apo A-I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells. PMID- 8500519 TI - Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. AB - The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development. PMID- 8500520 TI - Synovial IgG rheumatoid factors show evidence of an antigen-driven immune response and a shift in the V gene repertoire compared to IgM rheumatoid factors. AB - We have established IgG rheumatoid factor (RF)-secreting hybridoma cell lines from the synovial tissues of three patients from whom we have previously characterized several IgM RF. The IgG RF bind human and rabbit IgG and form intracellular complement-fixing complexes indicative of a self association process in vivo. Nucleotide sequence analysis revealed that two IgG RF used VHIII gene segments, while one used a VHI gene segment. The VL gene usage consisted of a V kappa 1, a V lambda 2 and a V kappa 4/V kappa 6 hybrid, confirming our previous findings that many different VL genes can contribute to RF specificity. Although the IgG RF used VH genes from the same families that dominated the IgM RF response, two of the actual gene segments employed were not found among the IgM RF. In contrast to IgM RF, which in general were not very mutated, the IgG RF showed somatic mutations characteristic of an antigen-driven immune response. PMID- 8500521 TI - Modulation of interferon-gamma receptor during human T lymphocyte alloactivation. AB - Previous work has shown that neutralization of physiologically secreted interferon(IFN)-gamma or blockade of its receptor during T lymphocyte activation inhibits both proliferation and cytotoxic T lymphocyte generation, suggesting that IFN-gamma plays a crucial role in T lymphocyte induction and differentiation. In this study, the kinetics of the surface expression of the 90 kDa IFN-gamma receptor (IFN-gamma R) was followed during human mixed lymphocyte reaction (MLR) to alloantigens. IFN-gamma R mRNA is constitutively expressed on resting peripheral blood lymphocytes emerging from nylon wood column (NW-PBL) and its expression increases two- to threefold on alloactivated NW-PBL. IFN-gamma R protein is poorly expressed on the membrane of resting CD3+ cells, but up modulates after 3-day MLR and sharply down-modulates at day 6. Both the p55 and the p75 chains of interleukin-2 receptor (IL-2R) were shown to up-modulate in parallel with IFN-gamma R, whereas they were still highly expressed at day 6. After alloactivation, IFN-gamma and IL-2 secretion starts at 24 h, peaks at day 3 and decreases just when IFN-gamma R and IL-2R begin to up-modulate. Proliferation peaks at day 6. Lastly, stimulation with distinct cell populations showed that the intensity of lymphocyte proliferation, IFN-gamma R membrane up-modulation, and IFN-gamma and IL-2 secretion are regulated in a parallel manner, thus suggesting that they are interrelated. Taken as whole these results demonstrate that increased expression of IFN-gamma R on T lymphocytes can be a critical event during their activation, and strongly support the hypothesis that IFN-gamma/IFN gamma R interaction provides a signal for its progression. PMID- 8500522 TI - Expression of complement receptor 2 (CR2) on HTLV-1-infected lymphocytes and transformed cell lines. AB - The expression of complement receptor 2 (CR2) has been demonstrated in established HTLV-1-transformed cell lines and in 12 studied de novo infected peripheral blood lymphocytes cultures, using 2 HTLV-1 sources. The simultaneous detection of CR2 and HTLV-1 antigens in both co-cultivated and supernatant infected peripheral blood lymphocytes suggest that the increased CR2 expression is in tandem with the increasing HTLV-1 antigen expression. CR2 up-regulation seen during polyclonal activation is presumably in response to a viral protein, although a cellular factor has not been ruled out. Increasing CR2 expression during early infection suggests its possible involvement in selection or development of subsequent transformation events. Variable levels of CR2 in immortalized cell lines argue against its obligate expression of function in the maintenance of the transformed state. The expression of CR2 in cellular activation of T cells may be stage restricted. This study also expands the cellular distribution for CR2. PMID- 8500523 TI - Systematic study of human alpha beta T cell receptor V segments shows allelic variations resulting in a large number of distinct T cell receptor haplotypes. AB - The variation of the alpha beta T cell receptor (TCR) results mainly from rearrangements of germ-line V, D and J elements combined with the processes of N- and P-region addition. In addition to this extensive diversity, diallelic polymorphism is also recognized in V regions of beta loci. Four such polymorphisms have previously been defined, but the full extent of such variation has not yet been established. To investigate allelic polymorphism, we used a strategy based V locus-specific polymerase chain reaction and single-strand conformation polymorphisms. Studying the two V beta 2 loci and the V alpha 8.1 locus, we found that all exhibited a coding polymorphism. One of the V beta 2 loci proved to be the first multiallele segment to be recognized, with three common variants. The second V beta 2 locus, for which none of the two alleles has been identified in cDNA, appeared in fact to be a V beta orphon, in abnormal location on the chromosome 9. A yeast artificial chromosome containing part of the TCRB locus allowed us to place the first V beta 2 segment on the known map to define haplotypes with two other polymorphic segments: V beta 1 and V beta 6.7. Multiple distinct haplotypes result from combinations between these polymorphic loci, showing that V beta regions are highly variable between individuals. Two alleles exist at the V alpha 8.1 segment and both are expressed. This represents the first example of a frequent coding polymorphism for TCRA gene. The distribution of allele frequencies for these segments suggest the action of balancing selection. These data add a further dimension to TCR polymorphism and suggest new candidates to explore TCR-encoded susceptibility to autoimmune diseases. PMID- 8500524 TI - Exon skipping without splice site mutation accounting for abnormal immunoglobulin chains in nonsecretory human myeloma. AB - The proliferating plasma cells of patient COM with nonsecretory myeloma synthesized truncated 42 kDa gamma 1 chains made of a complete constant region but devoid of variable domain. In the absence of light chain expression, the shortened gamma chains were retained intracellularly and were subsequently degraded within 12 h. COM neoplastic plasma cells contained short gamma 1 heavy chain transcripts in which the leader peptide exon was directly joined to the CH1 exon using the regular splice sites. However, study of the productive gamma gene showed that the skipped variable exon was bounded by normal splicing signals and that the adjacent intron organization was not altered. Since this unusual splicing pattern was maintained when COM gamma gene was transfected in murine plasmocytoma cells, exon skipping possibly relates to the modified structure of COM variable region. The latter showed a 2-base pair deletion introducing a translation frameshift in the VH region and a DNA insertion at the VH-DJH junction consisting in a perfect duplication of the first 54 nucleotides of the recombined DJH segment. The lack of light chain production by COM cells was explained by alterations of the variable region of the rearranged kappa gene leading to abnormally spliced transcripts. PMID- 8500525 TI - Alloreactive cytotoxic T cells can develop and function in mice lacking both CD4 and CD8. AB - Using the technique of homologous recombination in embryonic stem cells, a mouse strain without functional CD4 and CD8 genes has been generated. Surprisingly, these mice contain significant numbers of alpha beta T cells. Although mice deficient for CD8 only do not show any cytotoxic response when their T cells are stimulated with either alloantigen or viral antigen, the CD4-8- mice do generate alloreactive cytotoxic T cells. These cytotoxic T cells bear the alpha beta T cell receptor and recognize major histocompatibility complex class I antigens. In addition fully allogeneic skin transplants were rejected but skin transplants expressing only minor transplantation antigens were not. Virus-specific cytotoxic T lymphocytes were also not detected. It seems that alloreactive cytotoxic T cells can be induced and exert their effector function in vitro and in vivo in the absence of CD8, and that they can develop and mature in vivo without the CD8 molecule or the signals it might provide. PMID- 8500526 TI - The assembly of H2-Kb class I molecules translated in vitro requires oxidized glutathione and peptide. AB - Association of the mouse major histocompatibility complex (MHC) class I heavy chain H2-Kb with mouse beta 2-microglobulin (beta 2m) was studied in an in vitro translation system. Formation of stable class I complexes was found to be dependent on the presence of presentable peptides and oxidized glutathione, which promotes the formation of disulfide bridges. Translocation of peptides into microsomes was demonstrated by showing that a radioiodinated peptide containing an N-glycosylation acceptor site became glycosylated. Class I complex formation was observed only when heavy chains and beta 2m were translated simultaneously, and thus occurs in the microsomes and not after their solubilization. However, peptide binding takes place only after solubilization of the microsomes. The class I complexes translated in vitro show the same specificity and length preference for peptides as their counterparts in RMA-S cells. Assembly of in vitro translated class I complexes was found to occur also in the absence of peptides, resulting in the formation of unstable molecules that are stabilized by incubation with peptides. PMID- 8500527 TI - Agents that activate protein kinase C rescue sheep ileal Peyer's patch B cells from apoptosis. AB - The ileal Peyer's patch (PP) is the major site of B cell production and is a site of immunoglobulin gene diversification in the sheep. Within the ileal PP follicles there is both intense proliferation and death of B cells. We have previously demonstrated that most, if not all of this death can be attributed to apoptosis. Likewise, ileal PP B cells die rapidly by apoptosis in culture--after 6 h many cells appear pyknotic and about 50% of cellular DNA is fragmented. We now show that the DNA fragmentation and cell death of ileal PP B cells can be almost completely abrogated during the first 12 h of culture by the addition of the phorbol esters, phorbol dibutyrate (PBu2) or phorbol myristate acetate. This inhibition of apoptosis could be sustained for greater than 24 h by the concomitant addition of both PBu2 and the Ca2+ ionophore A23187. However, the rescue of B cells from apoptosis by PBu2, with or without Ca2+ ionophore, was prevented by macromolecular synthesis inhibitors or inhibitors of protein kinase C activation. Furthermore, treatment of cultures with PBu2, with or without Ca2+ ionophore, resulted in an activated B cell phenotype and a three- to fourfold increase in cell proliferation. We conclude that protein kinase C activation in conjunction with an increase in intracellular [Ca2+] can provide the signals necessary to rescue ileal PP B cells from apoptosis, and speculate that these ileal PP B cells are destined to die unless they receive a signal that rescues them from the death pathway. PMID- 8500528 TI - Membrane cofactor protein (MCP, CD46) in seminal plasma and on spermatozoa in normal and "sterile" subjects. AB - A sperm protein of molecular mass 43 kDa (the spermatozoa membrane cofactor protein, smMCP) and a seminal plasma protein of 60 kDa (ssMCP) were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with four monoclonal antibodies (mAb) against membrane cofactor protein (MCP, CD46). These proteins served as factor I cofactors for the cleavage of methylamine-treated C3 (C3ma), the activity of which was blocked by M75, an MCP cofactor-activity-blocking mAb. Thus, these semen proteins are antigenic and functional homologous of MCP. On SDS-PAGE analysis these MCP migrated as single band proteins which differed from the two-band forms of MCP expressed on other cells. smMCP was N-glycosylated but not O-glycosylated, while ssMCP was O glycosylated: after deglycosylation of these proteins bands were detected at 38 40 kDa and 43 kDa on SDS-PAGE, respectively. These semen MCP are therefore, structurally different from the conventional MCP. ssMCP in both normal and "sterile" subject groups was determined by sandwich enzyme-linked immunosorbent assay. Seminal plasma in the two groups contained 250-700 ng/ml ssMCP. The difference between the two groups was marginal, although samples from normal subjects tended to show higher concentrations of ssMCP than samples from "sterile" subjects. No molecular difference was observed with ssMCP and smMCP in the two groups by SDS-PAGE/immunoblotting analysis. Immunohistochemical analysis suggested that MCP was positive in glandular epithelial cells and the lumen of the prostate, and in most intra-lumen cells of the testis. Using antibody M177, solubilized prostate and testis were analyzed by immunoblotting and compared with other cell MCP. The major band of MCP in the testis, but not in the prostate, was of 60 kDa, which aligned with ssMCP. No band of testis or prostate MCP, however, aligned with smMCP. ssMCP may be produced in the testis, while the origin of smMCP remains unknown. We hypothesize that ssMCP is important in the survival of spermatozoa, protecting them against local secretion of immunoglobulin and complement in the female genital tract, and that smMCP, which is expressed on acrosome-reacted spermatozoa, plays an essential role in the interaction of spermatozoa with oocytes. PMID- 8500529 TI - HLA-DR beta chain residue 86 controls DR alpha beta dimer stability. AB - Major histocompatibility complex class II molecules exist in two forms, which can be distinguished on the basis of their stability in sodium dodecyl sulfate (SDS) as SDS-stable and SDS-unstable alpha beta dimers. The ratio of stable vs. unstable alpha beta dimers varies between murine H-2 alleles and isotypes, but the molecular basis for this observation is unknown. Here we show that for the human HLA-DRB1 and HLA-DRB3 gene products this ratio is controlled by the valine/glycine dimorphism at position 86. Haplotypes coding for DR beta chains with a valine at position 86 express higher numbers of stable dimers compared to similar haplotypes expressing DR beta chains with a glycine at that position. Reverse-phase high-performance liquid chromatography analysis of iodinated peptides, which were eluted from DR dimers with either a DRB1*1101 or a DRB1*1104 beta chain which differ only at position 86, indicated that these DR dimers contain (partially) distinct sets of peptides. The valine/glycine dimorphism is highly conserved, present in most HLA-DR alleles and influences peptide-binding. Analysis of the occurrence of the Val86 and the Gly86 gene products revealed that these are not equally present in the population. Depending on the DR specificity either the Val86 of Gly86 allelic variant is favored. Thus, the natural, highly conserved dimorphism at HLA-DR beta chain position 86 influences peptide selection. The dimorphism is therefore likely to influence antigen presentation and forms the molecular basis for the observed differences in stability of Val86- and Gly86-containing DR dimers in the presence of SDS. PMID- 8500530 TI - Induction of CD3 delta epsilon omega by phorbol 12-myristate 13-acetate. AB - The effect of phorbol 12-myristate 13-acetate (PMA) on the synthesis, assembly and processing of the components of the T cell receptor (TcR) was studied with special focus on the CD3 omega chain. Treatment of the human leukemic T cell line Jurkat with PMA increased the synthesis of the Ti alpha, CD3 gamma and CG3 zeta chains two- to threefold and the synthesis of Ti beta and CD3 delta epsilon omega complexes five- to sevenfold as assessed by metabolic labeling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by scanning densitometry. The amount of total assembled TcR complexes increased approximately threefold and the maturation of the TcR was not affected as determined by analysis of oligosaccharide side chain processing in the Golgi apparatus. Activation of Jurkat cells with anti-CD3 monoclonal antibody, calcium ionophore, or mitogenic lectins did not affect the synthesis of the TcR components. In other cells studied (the human leukemic T cell line CEM, a panel of variants of the Jurkat T cell line and peripheral blood mononuclear cells) PMA also increased the synthesis of the TcR components. However, for all cell lines studied the amount of TcR complexes expressed on the cell surface was decreased after 16 h of PMA treatment. Based on these results we propose a role of CD3 omega in retention of TcR complexes. From PMA-treated CEM cells more than 50-fold the amount of CD3 delta epsilon omega complexes was immunoprecipitated as compared to the amount obtained from untreated Jurkat cells, and these observations indicate that the CEM cell line may be a qualified candidate for purification of CD3 omega. PMID- 8500531 TI - Mouse Crry/p65 is a regulator of the alternative pathway of complement activation. AB - Like man, mouse has evolved a unique set of regulatory proteins which provide protection from complement-mediated damage to self membranes. The recently described mouse protein Crry/p65 has been shown to inhibit classical complement pathway C3 deposition on cell membranes in which it is expressed. In two distinct experimental systems, we now further delineate the regulatory activity of Crry/p65 and demonstrate its inhibitory effect on alternative complement pathway C3 activation. First, significant inhibition of mouse alternative pathway C3 deposition was demonstrated on neuraminidase-treated human K562 cells expressing recombinant Crry/p65. Second, using a baculovirus technique, recombinant Crry/p65 was synthesized as a soluble molecule and then purified. This molecule was found to inhibit mouse C3 deposition on the surface of zymosan, a potent alternative complement pathway activator. These studies, combined with our earlier findings, demonstrate that Crry/p65 can regulate both the classical and alternative complement pathways. Crry/p65 must, therefore, exert its effects prior to, or at the level of, the C3 convertases, in a fashion similar to that of human membrane cofactor protein and/or decay-accelerating factor. These studies provide further proof of the hypothesis that Crry/p65 is an evolutionarily unique, complement regulatory protein which has developed in mouse. PMID- 8500532 TI - Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D. AB - Mouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r-adipsin) were produced in rabbits. Anti-r-adipsin IgG was shown to bind to radiolabeled r-adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of anti-r adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4-h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti-r-adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti-r-adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo. PMID- 8500533 TI - T cell receptor beta chain dimers on immature thymocytes from normal mice. AB - During T cell development the T cell receptor (TCR) beta chain is expressed before the TCR alpha chain. Experiments in TCR beta transgenic severe combined immune deficiency (SCID) mice have shown that the TCR beta protein can be expressed on the cell surface of immature thymocytes in the absence of the TCR alpha chain and that the TCR beta protein controls T cell development with regard to cell number, CD4/CD8 expression and allelic exclusion of the TCR beta chain. Subsequent experiments have shown that on the surface of thymocytes from TCR beta transgenic SCID mice the TCR beta protein can be expressed in a monomeric and dimeric form whereas only the dimeric form was found on the surface of a TCR beta transfected, immature T cell line. The results presented here show that normal thymocytes from 16-day-old fetuses likewise express only the dimeric form and that the monomeric form on the surface of thymocytes from transgenic mice results from glycosyl phosphatidylinositol linkage. Our results show for the first time that under physiological conditions a TCR beta dimer can be expressed on the cell surface without the TCR alpha chain. PMID- 8500534 TI - In vivo priming effect during various stages of ontogeny of an influenza A virus nucleoprotein peptide. AB - In vivo priming of cytotoxic T lymphocytes (CTL) by an influenza virus nucleoprotein (NP) peptide was studied at various stages of development. Adult mice immunized twice with the NP peptide in complete Freund's adjuvant and incomplete Freund's adjuvant, respectively, produce significant CTL responses. Neonates immunized at birth with large amounts of NP peptide and boosted twice with the peptide during adulthood, also mount a weak but significant CTL response. By contrast, offspring from mothers immunized with the NP peptide at days 15, 17, and 19 of pregnancy showed unresponsiveness to the peptide subsequent to a similar regimen of peptide immunization at the age of 1 month. The data indicate that the contact of T cell precursors with antigen during fetal life induces CTL tolerance, whereas, after birth the precursors are not susceptible to tolerogenic signals. PMID- 8500535 TI - The gene loci for immunoglobulin heavy chains in precursor B cell lines from a patient with severe combined immunodeficiency appear able to participate in DNA rearrangement but have a germ-line configuration. AB - In a previous study (Immunogenetics 1988. 27:330) with Epstein-Barr virus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the numbers of B cells and T cells were markedly reduced. Although based on their surface markers these cell lines appeared to be at an early stage of B cell differentiation, the gene loci for immunoglobulin heavy chains (IgH) retained the germ-line configuration on both chromosomes in almost all the transformants. In this study, we found that the enhancer sequence, located between the JH and mu genes, was hypomethylated and an abundance of the germ-line Cmu transcript was detected in these cell lines by Northern hybridization. These results suggest that the chromatin structure of the IgH gene locus in these cell lines is accessible to VDJ recombinase and is able to participate fully in DNA rearrangement. By contrast, we did not detect transcripts of the RAG-1 and RAG-2 genes, which are required for V(D)J recombination at gene loci for immunoglobulin and T cell receptors. Thus, it seems likely that these cell lines fail to initiate the V(D)J recombination process because of some deficiency in the formation of VDJ recombinase, which includes the inability to express RAG genes. PMID- 8500536 TI - Head posture in obstructive sleep apnoea. AB - In growing subjects, obstruction of the upper airway may lead to excessive vertical facial development. According to the soft-tissue stretching hypothesis (Solow and Kreiborg, 1977) this could be due to an increased cranio-cervical angulation triggered by the airway obstruction. The present study aimed to examine the effect of airway obstruction on cranio-cervical posture in a sample of adult patients with severe obstructive sleep apnoea (OSA). Lateral cephalometric radiographs taken in the natural head position (mirror position) were obtained from 50 male patients aged 28-70 with polysomnographic diagnosis of obstructive sleep apnoea. The Apnoea Index ranged from 21 to 98 episodes per hour with a mean of 54.6. Control samples were available from previous cephalometric studies of head posture in five samples of healthy subjects and one sample of congenitally blind subjects. The average cranio-cervical angle, NSL/OPT, was found to be extremely large (mean 104.1, SD 9.1) exceeding the average values in the control samples by 1-2 standard deviations (P < 0.001). It is suggested that the large cranio-cervical angle in OSA patients is a physiological adaptation aiming to maintain airway adequacy while the head, and thus the visual axis, is kept in its natural relationship to the true vertical. The findings thus provide evidence for the hypothesis that upper airway obstruction may trigger an increase in the cranio-cervical angulation. PMID- 8500537 TI - Electrothermal debonding of ceramic brackets. An in vitro study. AB - Two different kinds of devices for electrothermal debonding of ceramic brackets are evaluated. Thirty human premolars were bonded with two types of ceramic brackets. Both devices were tested for electrothermal removal of the two bracket types. The pulpal wall temperature increase during electrothermal debonding was recorded in vitro under various circumstances. After debonding, the fracture site was located. The data were compared to the temperature rise after simulated exposure of the teeth to warm beverages. Irreversible pulp damage due to electrothermal debonding of ceramic brackets with both instruments is not to be expected because the obtained results stayed below established primate threshold temperatures and significantly below that of the stimulated control groups. A significant difference was noted when air cooling was initiated during electrothermal debonding. Fracture site location was significantly different in the two ceramic bracket types after electrothermal debonding. PMID- 8500538 TI - The tensile bond strength of new and rebonded stainless steel orthodontic brackets. AB - The study investigated the effect on the tensile/peel bond strength of the variables associated with the bracket base, the enamel surface, and the type of adhesive when both new and used brackets were rebonded to a previously bonded enamel surface. The tensile/peel bond strength was firstly evaluated for three different types of stainless steel orthodontic bracket/base combinations. The cast integral base gave a significantly lower bond strength than the foil-mesh and photo-etched bases. Following debonding, a group of new brackets were bonded to the teeth using a chemically-activated or a light-cured adhesive. The old adhesive had been removed from the enamel by either a hand scaler or a tungsten carbide bur. The rebonded new brackets demonstrated a small, but statistically significant fall in bond strength. No differences were found between the enamel preparations or the adhesives. A further group of previously debonded brackets were rebonded to the same teeth. The bracket bases were prepared by either smoothing with a green stone or heating in a bunsen flame followed by sandblasting and electropolishing. Highly significant falls in bond strength were obtained with all the bases. No significant differences were found between the two methods of bracket preparation. PMID- 8500539 TI - Reliability of landmark recording on film and digital lateral cephalograms. AB - The aims of this study were: (a) to evaluate reliability of landmark location in digital processed images of film cephalograms of varying quality with that obtained in the films, and (b) to evaluate the pattern of error in landmark location with the two techniques. The sample consisted of 20 original cephalograms (OQ), 10 'high' quality images (Q1), and 10 'average' quality images (Q2). Measurements on films were performed using a digitizer connected to a PC and controlled by a cephalometric program, while measurements on digital images were obtained using a mouse and a cephalometric program for landmark sampling. To assess the digital images (DQ), the films were video recorded (B/W video camera), digitized (matrix = 512 x 512 x 8), stored in a PC, and displayed on a quality monitor. Fifteen cephalometric landmarks were recorded by three observers twice on each of the 20 images by the two methods. Mean x- and y-values were calculated for each landmark to obtain the best estimate of each landmark position. Comparisons between the OQ and DQ group, and between the subgroups of different film quality were performed (Wilcoxon's rank sum test). In general, measurements from the OQ images were more reliable than from the DQ images (P < 0.02). The pattern of recording error also differed between the two techniques, OQ images being more reliable along the x-axis (P < 0.01), while along the y-axis, reliability was not significantly different between the two groups. Q1 and Q2 images did not differ significantly in either group (P > 0.05). A difference was, however, observed between OQ2 and DQ2 images (P < 0.02), while this was not the case for OQ1 and DQ1 images. The generally lower reliability for measurements on the digital images could be ascribed to the much larger error, especially in the y-axis, for the Q2 images. PMID- 8500540 TI - Comparison of human dental and craniofacial maturation on prenatal profile radiographs. AB - The present study reveals new data concerning the prenatal interrelationship between maturation of teeth and basicranial bones. By using radiographs of the mid-sagittal tissue segment of 43 human craniums, the developmental relationship between a well-defined stage of the central maxillary incisor development and the development of the basicranium was determined. Histological controls were performed to verify the radiographic findings. The study shows a close connection between the incisor development and the cranial development. Furthermore, comparisons are performed to the generally used parameters for prenatal growth, i.e. the crown-rump length (CRL) and the gestational age (GA). A thorough understanding of developmental interactions between the teeth and cranium is important for the understanding of normal, as well as pathological craniofacial development, including tooth development. PMID- 8500541 TI - Orthodontic tooth movement into edentulous areas with reduced bone height. An experimental study in the dog. AB - The present study was performed in order to test the hypothesis that the height of supporting bone and connective tissue attachment will be maintained around teeth bodily moved into areas of reduced bone height. During a pre-experimental period, areas with markedly reduced bone height were produced in the mandible of 4 beagle dogs through extraction of the 4th premolars and subsequent surgical reduction of the bone height in the extracted sites to a level corresponding to half the root length of the 3rd premolar. Following healing, one of the third premolars was bodily moved in a distal direction into the area of reduced bone height, while the contralateral premolar served as a non-moved control. After 6 months of active tooth movement, the teeth were retained in their new position for a further 2 months before biopsies of test and control tooth sites were sampled. Radiographic evaluation showed that a bodily movement had been achieved with no or only minimal vertical displacement of the teeth. The histological analysis revealed that none of the teeth, orthodontically moved or not, had experienced loss of connective tissue attachment. Although a greater distance between the cemento-enamel junction and the bone crest was found on the pressure side of the orthodontically moved test teeth in comparison to the contralateral, non-moved control teeth, the bone level at all test teeth was more coronally positioned than the original, reduced bone level in the area into which the test teeth had been moved. Hence, these findings indicate that a tooth with a normal height of periodontal support can be orthodontically moved into an area of markedly reduced bone height with maintained height of the supporting apparatus. PMID- 8500542 TI - A three-dimensional analysis of bone and soft tissue to bone ratio of movements in 17 Skeletal II patients following orthognathic surgery. AB - The three-dimensional changes in the bone and the ratio of soft tissue to bone movement were investigated in a group of 17 Skeletal II patients following orthognathic surgery. CT scans were taken for each patient pre-operatively and 1 year post-operatively. The scans were superimposed, radial measurements calculated, and the changes illustrated by two separate colour scales. There was a constant ratio of movement over the maxillae with the central part of the upper lip being moved in a 1:1 ratio, increasing to a 1.25:1 ratio over the canine regions and 1.5:1 ratio over the paranasal areas. In the mandible there was a constant ratio of 1.25:1 over the chin, mentalis, and canine regions bilaterally. The ratio reduced to 1:1 over the body of the mandible. PMID- 8500543 TI - Monocyte-mediated restoration of density-dependent growth control and induction of cell death in tumor cell populations. AB - It is shown in a serum-free system with human cells that during monocyte/tumor cell interactions signals are generated which restore the principles of density dependent inhibition of growth in tumor cell populations. Tumor cells that fail to comply with these principles are induced to die. This cell death is an active process in target cells involving protein biosynthesis and tumor cell-derived signals. PMID- 8500544 TI - Melatonin inhibits proliferation and melanogenesis in rodent melanoma cells. AB - The effects of melatonin on proliferation and on the induction of melanogenesis in rodent melanoma cells were investigated. It was found that melatonin at low concentrations (0.1-10 nM) inhibited cell growth but had no effect on melanogenesis, while at high concentrations (> or = 0.1 microM) it inhibited the induction of melanogenesis but not cell growth. These effects were specific since corresponding concentrations of the direct precursor and product of melatonin degradation N-acetylserotonin (N-Ac-5HT) and 5-methoxytryptamine (5MT), respectively, did not have any effect on cell proliferation or melanogenesis. At very high concentration (100 microM) both N-Ac-5HT and melatonin could stimulate melanoma proliferation while 5MT inhibited it. The demonstration of differential and unparalleled effects of melatonin on cell proliferation and melanogenesis suggests that melatonin can regulate or modify both processes via different mechanisms. PMID- 8500545 TI - Identification of Drosophila wing imaginal disc proteins by two-dimensional gel analysis and microsequencing. AB - We have combined high-resolution two-dimensional (2D) gel electrophoresis with microsequencing techniques in order to identify proteins in the 2D gel database of wing imaginal discs of Drosophila melanogaster. First, a high-resolution 2D gel separation pattern of the [35S]methionine-labeled polypeptides from CME W2 cells, a stable cell line derived from wing imaginal discs, is presented and compared with the standard pattern of polypeptides of wing imaginal discs. These studies reveal significant qualitative and quantitative alterations in polypeptide expression between both samples. Second, we carried 2D PAGE to the preparative level using the CME W2 cell line mixed with radioactively labeled wing imaginal discs in order to identify some common polypeptides and subsequently characterized them by microsequencing techniques. Using these methods we obtained partial amino acid sequences of several Drosophila proteins of the 2D gel protein database. As an illustration we present 12 of them: 8 corresponding to proteins already known in Drosophila and the 4 showing homologies with proteins of other organisms. PMID- 8500546 TI - Gene modulation accompanying differentiation of normal versus malignant keratinocytes. AB - Using tetradecanoylphorbol 13-acetate (TPA), a known inducer of epithelial cell differentiation, and Northern blot analysis, we investigated in normal versus well-differentiated malignant keratinocytes the modulation of genes implicated in their growth or differentiated function. In normal keratinocytes transient c-fos induction was detected within 30 min after stimulation and was followed by rapid down regulation of the proto-oncogenes c-myc and epidermal growth factor receptor. Within hours after stimulation mRNA levels for three well-characterized differentiated keratinocyte products, involucrin, interleukin-1 beta (IL1-beta), and fibronectin, were induced, as were those for a growth arrest and DNA damage inducible (GADD 153) gene and a small proline-rich (SPR1) gene, both known to be associated with differentiation but with of as yet unknown functions. Heat shock protein 70 gene was initially down regulated and was induced only after 48 h. The well-differentiated malignant keratinocyte cell line differed in that the c-fos, GADD, SPR1, and IL1-beta genes had several-fold higher induction, but involucrin mRNA was undetectable and fibronectin mRNA was only minimally induced after TPA stimulation. Malignant cells reached terminal differentiation faster than normal keratinocytes as measured by inability to exclude trypan blue dye, and in situ hybridization using a riboprobe for the differentiation-associated SPR1 gene showed that normal keratinocytes constitutively express this transcript while malignant keratinocytes with virtually identical morphology and growth rate do not. These studies greatly expand our understanding of gene activation and down regulation during normal keratinocyte differentiation and imply that a malignant cell line, even when retaining the phenotype of normal cells, differs in its response to outside stimuli, furnishing at best an imperfect model for investigating the molecular mechanisms of cellular differentiation. PMID- 8500547 TI - Modulation of SPARC expression during butyrate-induced terminal differentiation of cultured human keratinocytes: regulation via a TGF-beta-dependent pathway. AB - Expression of SPARC (secreted protein acidic and rich in cysteine), a 43-kDa extracellular matrix-associated glycoprotein involved in tissue remodeling, was quantitated during normal human keratinocyte (NHK) growth in culture and as a function of sodium n-butyrate (NaB)-induced differentiation to mature enucleate cornified envelopes (CEs). Low levels of SPARC expression were observed in the basal-like cells of control NHKs, with isolated cells showing intense SPARC expression on the ventral surface. After addition of NaB, SPARC expression increased and the pattern of expression shifted to one involving predominantly suprabasal cells (i.e., spinous cells, pre-CEs, and mature CEs). Dense deposits of SPARC often surrounded the mature CEs. Flow cytometric analysis indicated that approximately 13% of NHKs expressed SPARC within 24 h of seeding into culture. This fraction of SPARC+ cells increased with time and peaked immediately postconfluence (31.3 +/- 6.3% SPARC+). Cellular SPARC expression then decreased to baseline levels during entrance into plateau phase growth. SPARC was detectable in all phases of the cell cycle. SPARC levels were more intense and heterogeneous within the G2/M and G1 phases while S phase cells exhibited relatively homogeneous, low intensity, SPARC expression. During NaB-induced NHK differentiation, SPARC intracellular content increased prior to the onset of CE formation (i.e., 2 days after its addition) followed by a period of extracellular accumulation which coincided with the time of maximal CE generation (i.e., Days 4 and 5 after NaB addition). Correlation of cell size with anti-SPARC immunoreactivity revealed a predominance of SPARC expression in cells with a suprabasal phenotype. NHKs cultured on fibronectin (FN), an established modulator of epidermal cell maturation in vitro, showed a similar response to NaB. In general, however, the level of NaB-induced SPARC expression was considerably reduced in FN cultures correlating with a lower efficiency of CE formation. Induced SPARC expression was, in large part, dependent on autocrine transforming growth factor-beta (TGF-beta) production since incubation in the presence of NaB+neutralizing antibodies to TGF-beta inhibited both the expression of SPARC by 72% and development of mature CEs. PMID- 8500548 TI - Regulation of collagen synthesis in human dermal fibroblasts in contracted collagen gels by ascorbic acid, growth factors, and inhibitors of lipid peroxidation. AB - Ascorbic acid has been shown to stimulate collagen synthesis in monolayer cultures of human dermal fibroblasts. In the present studies, we examined whether the presence of a collagen matrix influences this response of dermal fibroblasts to ascorbic acid. Fibroblasts and collagen were mixed and allowed to gel and contract for 6 days to form a matrix prior to determining the concentration and time dependence for ascorbic acid to affect collagen synthesis by fibroblasts within the matrix. Collagen synthesis was stimulated at levels at or above 10 microM ascorbic acid and was maximal after 2 days of treatment. This concentration and time dependence is similar to that of cells grown in monolayer cultures. The effects of transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) were also examined in this model. TGF-beta increased and FGF inhibited collagen synthesis in the gels, as has been shown for cells in monolayer cultures. The effects of potential inhibitors of lipid peroxidation induced by ascorbic acid were also examined in these matrices and compared to previous results obtained in monolayer cultures. Propyl gallate, cobalt chloride, alpha,alpha-dipyridyl, and alpha-tocopherol inhibited the ascorbic acid-mediated stimulation of collagen synthesis while mannitol had no effect. Natural retinoids inhibited total protein synthesis without the specific effect on collagen synthesis that was seen in monolayer cultures. These results indicate that ascorbic acid stimulates collagen synthesis in fibroblasts grown in a collagen matrix in a manner similar to that found in monolayer cultures. In contracting collagen gels, however, the magnitude of the effect is less and retinoids do not specifically inhibit collagen synthesis. PMID- 8500549 TI - Growth and physiological functions of vascular endothelial cells in a new serum free medium (SFM). AB - Endothelial cells grown in vitro are widely used for the study of vascular physiology and pathology. The high levels of serum supplementation normally used in endothelial cell culture may create problems in experimental design or in interpretation of results. A serum-free medium (SFM) has been designed specifically for culture of nonhuman vascular endothelial cells. Growth as well as retention of various physiological markers in this medium was demonstrated in large-vessel endothelial cells from bovine, porcine, ovine, and canine species. Cells from all species tested took up DiI-acetylated LDL. Factor VIII-related antigen was demonstrated in cultures of bovine and canine cells. Bovine and porcine cells were shown to have retained the ability to produce prostacyclin. Further supplementation of the SFM with various lipid-containing additives failed to stimulate either growth or prostacyclin production. PDGF produced by bovine, porcine, and canine endothelial cells was measured and found to be present at lower concentration than in serum supplemented cultures. All cells grown in SFM exhibited the histiotypic "cobblestone" morphology normally associated with cultured endothelial cells. While not optimized for culture of human endothelial cells, short-term growth < or = 4 passages) of human umbilical vein endothelial cells was achieved by supplementing the SFM with hydrocortisone, bovine pituitary extract, and epidermal growth factor. PMID- 8500550 TI - DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death. AB - Cytotoxic T lymphocyte (CTL)-mediated lysis is accompanied by fragmentation of target cell DNA into an oligonucleosome ladder, a hallmark of apoptosis. Is this a fortuitous coincidence, or could CTL be inducing lysis by activation of the suicide signal? In this report we demonstrate that CTL-mediated target cell death can be blocked with the drug aurintricarboxylic acid (ATA). The abrogation of death correlates with the inhibition of DNA fragmentation. While ATA prevented DNA fragmentation, it failed to significantly alter protein, RNA, or DNA synthesis in the cell lines over the dose range used. In addition, there was no inhibition of cell-cell interaction or granule exocytosis during CTL-mediated killing. ATA also significantly inhibited the cytolysis and DNA fragmentation mediated by isolated cytolytic granules, as well as the granular protein fragmentin. We developed an assay in which target cells could be separated from CTL after binding and programming for lysis. Once they had received the "kiss of death," target cells could be rescued from lysis (as indicated by inhibition of DNA fragmentation and increased target cell viability) by treatment with ATA. These results suggest that ATA blocks target cell death by inhibition of DNA fragmentation, and further, that chromatin degradation is a cause rather than a result of cell death in CTL-mediated lysis. PMID- 8500551 TI - Antiproliferative effect of DNA polymerase alpha antisense oligodeoxynucleotides on breast cancer cells. AB - Antisense oligonucleotides appear to offer considerable promise as sequence specific inhibitors of gene expression. Different cellular targets for oligodeoxynucleotides with oncologic interest have been identified such as oncogenes, growth factors, and cell cycle-related genes. DNA polymerase alpha (pol alpha) plays a relevant role in DNA synthesis and cell proliferation. Pol alpha gene expression is constitutive throughout the cell cycle and its mRNA content and activity are related to the growth rate and neoplastic phenotype. The effects of a 18-mer pol alpha antisense oligomer on the proliferation of the MDA MB 231 breast cancer cell line have been investigated. After 48 h in culture with oligomers (10 microM), about 50% growth inhibition was observed in antisense treated cells, as evaluated by 3-(4,5-dimethythiazol-2yl)-2,5-diphenyltetrazolium bromide assay and cell count. [3H]Thymidine incorporation exhibited a 90% inhibition of DNA synthesis associated to 64% accumulation of cells at the G1-S border of the cycle as by flow cytometry, at 24 h. Northern hybridization and SDS PAGE of immunoprecipitated MDA-MB 231 cell lysates revealed a decreased expression of pol alpha mRNA and a reduction of the 180-kDa polypeptide, respectively. Collectively, the data further confirm the relevance of pol alpha in the replicative cycle, as well as strengthen the potentiality of the antisense strategy for the control of gene expression and cell growth. PMID- 8500552 TI - Evidence for transmembrane anchoring of extracellular matrix at acetylcholine receptor clusters. AB - Clusters of nicotinic acetylcholine receptor (AChR) in cultured rat myotubes are organized into rectilinear arrays of receptor-rich and receptor-poor domains. Extracellular matrix (ECM) molecules, including fibronectin, heparan sulfate proteoglycan, laminin, and type IV collagen, codistribute with AChR in these clusters. We have examined the stability of this association. We disrupted the AChR clusters in intact myotubes with sodium azide, an energy metabolism inhibitor, and with culture medium free of Ca2+. We also altered or extracted proteins from detergent-isolated AChR clusters by treating with buffers of low ionic strength or alkaline pH or with insoluble chymotrypsin. Each of these treatments dispersed AChR clusters and, simultaneously, caused fibronectin, heparan sulfate proteoglycan, laminin, and type IV collagen to disperse from AChR rich strips of membrane. Control experiments indicated that insoluble chymotrypsin had no direct effect on the ECM at AChR clusters. It did, however, remove spectrin and the receptor-associated 58-kDa protein from the cytoplasmic surface of receptor clusters. Thus, the ECM at AChR clusters is disrupted by an agent acting at the cytoplasmic surface of the membrane. We discuss the possibility that both AChR and ECM are bound to a common membrane skeleton and the implications this may have for synaptogenesis. PMID- 8500553 TI - Stage-specific expression and localization of MENT, a nuclear protein associated with chromatin condensation in terminally differentiating avian erythroid cells. AB - Polyclonal antibodies have been raised against a non-histone protein (MENT) which has been previously shown to be associated with the repressed chromatin of mature chicken erythrocytes and to promote the in vitro condensation of chromatin of immature erythrocyte nuclei. Here we report that the expression pattern of MENT closely follows chromatin condensation in maturing avian erythrocytes of definitive and primary lineages. Accumulation of MENT correlates more strongly with chromatin condensation than does accumulation of histone H5. In addition to being present in erythrocytes, the protein was also found in neutrophil nuclei and an immunofluorescence reaction was observed with embryonic (nucleated) thrombocytes. MENT was not detected in other chicken tissues (brain, liver, testis). In intact erythrocytes, MENT immunofluorescence was found in foci close to the nuclear periphery, while in isolated, decondensed nuclei, the fluorescence signal was uniformly distributed. In neutrophil nuclei, containing approximately 10 times more MENT than adult erythrocytes, intense staining associated with the peripheral heterochromatin was observed. These findings are discussed in regard to a possible mechanism for chromatin condensation by MENT. PMID- 8500554 TI - Cholesterol content of the rat lens is lowered by administration of simvastatin, but not by pravastatin. AB - The influence of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors pravastatin and simvastatin on lens cholesterol metabolism was investigated in the rat. Short-term organ culture experiments with explanted lenses from 21-day-old Wistar rats showed that simvastatin was at least 35 times more effective than pravastatin in inhibiting cholesterol synthesis. In vivo the cholesterol content of the rat lens increased linearly with age. Experiments were designed to answer the question whether simvastatin and pravastatin inhibit lens cholesterol synthesis in vivo, which would result in a reduced cholesterol accumulation in the lens with age. Young Wistar rats were weaned at an age of 21 days and had ad libitum access to a chow supplemented with 10-100 mg vastatin kg 1 (drug consumption: 1.5-15 mg vastatin kg-1 body weight day-1, respectively) or no additions for 3 weeks. Both drugs induced the HMG-CoA reductase activity in rat liver microsomes (isolated after 1, 2 and 3 weeks of treatment) to a similar extent. This indicates that the two drugs inhibited hepatic cholesterol synthesis to a comparable extent. During the whole treatment period no significant differences between control and drug-treated animals could be observed when the wet weight and protein content of the lenses were considered. However, a striking difference between the control group and pravastatin group (50 mg drug kg-1 diet) on the one hand and the simvastatin group (50 mg drug kg-1 diet) on the other was observed when the cholesterol content of the lenses were compared as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500555 TI - Separation of the rabbit ciliary body epithelial layers in viable form: identification of differences in bicarbonate transport. AB - Sections of whole ciliary (CB) dissected from Dutch belted rabbits were incubated for 2 hr at 36 degrees C in a 30 microM Ca2+ Ringer's. This incubation resulted in the spontaneous dissociation of the two cell layers comprising this epithelium, each remaining firmly cohesive with its own basement membrane. The inner limiting membrane with its adherent non-pigmented epithelium (NPE) was then mechanically removed from the surface exposing the apical surface of the pigmented epithelium (PE). Ultrastructural examination revealed no noxious effects in most cells although gross morphological changes in the NPE cells were noted. The newly separated layers were loaded with the cell-permeable acetoxymethyl ester form of the fluorescent probe BCECF. Most cells of both layers acquired stable BCECF fluorescence indicating viability. To achieve a preliminary evaluation of differences in PE and NPE bicarbonate transport, dye loaded tissues were perfused in a flow-through chamber which was mounted on a microscope equipped for quantitative epifluorescence. The intracellular pH (pHi) of groups of cells (5-10) was derived from the ratio of emission intensities generated by excitations at 490 and 440 nm. In Hepes-buffered Ringer's the pHis for the PE and NPE were 7.20 +/- 0.10 and 7.33 +/- 0.14 (+/- S.D., n = 6), respectively. Replacement of 28 mM Hepes by 28 mM HCO3-/5% CO2 led to a 0.13 pHi increase in the PE and a decrease of 0.27 U in the NPE. The pHi responses of the two cell layers to removal and/or reintroduction of Na+ and/or Cl- were also highly dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500556 TI - Development and fate of interphotoreceptor matrix components during dysplastic photoreceptor differentiation: a lectin cytochemical study of rod-cone dysplasia 1. AB - The autosomal recessive retinal degeneration rod-cone dysplasia 1 (rcd1) affects Irish setter dogs during early postnatal development. The disease is the result of a cyclic guanosine monophosphate metabolic abnormality and morphological evidence of disease onset correlates with initiation of photoreceptor outer segment formation. Rod photoreceptors are affected earlier and more severely than cones. Postnatal development of specific interphotoreceptor matrix (IPM) constituents was examined in tissue sections and extracted matrix preparations from control and affected dogs using peanut agglutinin (PNA) and wheat germ agglutinin (WGA) lectin cytochemistry. These lectins bind two photoreceptor specific domains through their affinity for specific terminal carbohydrate sequences present on proteoglycans and glycoproteins in the IPM. Development of rod and cone matrix domains in the normal dog occurs in parallel to the development and differentiation of outer segments (between postnatal days 10 and 60 in the dog); during this period the lectin specificity or distribution in the rcd1 retina did not differ from the normal control. Structural changes of the matrix domains were present and reflected the morphological alterations of the diseased and degenerating photoreceptor cells. Cone domains were present around severely degenerated cone cells as long as these cells were found within the interphotoreceptor space. The matrix domain investing surviving cones did not differ significantly from the normal to indicate an altered binding specificity or structure. The rod domain was still present around rod inner segments in late degeneration. The matrix domains are present in the IPM as long as the photoreceptor cell body remains in the interphotoreceptor space; photoreceptor loss results in disappearance of the matrix. We detected no change in matrix composition or distribution with the lectins used, either during development or degeneration, despite the serious biochemical and structural abnormalities of the photoreceptor cell that are characteristic of the disease. PMID- 8500557 TI - Hyperbaric oxygen inhibits the growth of cultured rabbit lens epithelial cells without affecting glutathione level. AB - Studies on human patients and experimental animals indicate that hyperbaric O2 can opacify the lens nucleus and damage the lens epithelium in vivo. Here we investigate the effects of hyperbaric O2 on cultured rabbit lens epithelial cells (LECs). When the cells were exposed to 50 atm O2 (99% O2 + 1% CO2) for 3 hr there were no immediate effects on morphology, viability and transport processes (uptake of 86Rb and 14C-alpha AIB). In addition, the O2 treatment did not lower the high level of reduced glutathione or increase the low level of oxidized glutathione. However, 50 atm O2 did produce a near doubling in the glycolytic rate which maintained ATP at levels only slightly lower than normal. Although the 3-hr O2 treatment was not lethal, it completely inhibited cell division for 2 days. After 2 days, growth was initiated and, at day 7 the rate of growth was faster than the controls (control cells were treated with ambient air or 50 atm N2 for 3 hr). Cells treated with 8 atm O2 for 3 hr exhibited a slowed rate of growth, relative to controls, while exposure to 2 atm O2, did not inhibit mitosis. Changes in morphology (multilayering and elongation) of cells exposed to 50 atm O2, but not the controls, were evident 7 days after the 3-hr exposure. The incorporation of [35S]methionine into individual polypeptides and [3H]thymidine into DNA was significantly inhibited immediately following a 3-hr treatment with 50 atm O2, but both parameters recovered within 2 days. DNA strand breaks were observed in LECs following hyperbaric O2 treatment as low as 4 atm O2 for 3 hr and increased with higher pressures of O2, but not N2. Treatment with 50 atm O2 nearly doubled the activity of the DNA repair enzyme, poly-ADP-ribose polymerase, and decreased the level of its substrate NAD+; the latter effect was reduced by 3 aminobenzamide, an inhibitor of the enzyme. Thus, although LECs tolerated brief exposures to high pressures of O2 without cell death, DNA damage occurred at relatively low pressures of O2. All of the effects of hyperbaric O2 on LECs occurred without any alteration of the normal levels of reduced and oxidized glutathione. It appears that GSH is important in maintaining cell viability during exposure to an elevated level of O2, but that it is incapable of preventing O2-induced effects on growth and DNA. PMID- 8500558 TI - Molecular cloning and nucleotide sequence of a cDNA encoding recoverin from human retina. AB - In the process of photoreceptor signal transduction, light initiates an enzymatic cascade that leads to hydrolysis of cyclic GMP (cGMP) and closure of cGMP-gated sodium-calcium channels resulting in photoreceptor hyperpolarization. Recoverin is a calcium-binding protein that is thought to reverse the effects of light on cGMP levels by activating guanylate cyclase. Guanylate cyclase produces cGMP to overcome the cGMP-hydrolysing effect of phosphodiesterase, and reopens the sodium calcium channels in photoreceptor outer segments. We have cloned and sequenced a cDNA encoding recoverin in human retina. The human nucleotide sequence is 88% identical to the bovine sequence, and contains a 600-base pair (bp) open reading frame encoding 200 amino acids. In situ hybridization of cultured Y79 human retinoblastoma cells with a radioactive recoverin cDNA probe showed intense, specific labeling of the cytoplasm, indicating the presence of mRNA encoding recoverin. Direct sequencing of a Y79 retinoblastoma cDNA polymerase chain reaction (PCR) product confirmed the presence of recoverin in this human cell line. PMID- 8500559 TI - Regional differences within the external 'duct' of the rat exorbital lacrimal gland. AB - The lacrimal cord is the fibrous structure that extends between the rat exorbital lacrimal gland and the eyelid. Disagreement exists about the number of ducts it contains and with which lid the orifice is associated. Therefore, 18 lacrimal cords from adult rats were studied by light microscopy. Additionally, in five specimens the continuations of the major ducts were observed immediately intraglandularly. Adjacent to the exorbital lacrimal gland, the lacrimal cord may contain six or more ducts. Farther toward the eye, it has five, four, and then three ducts; the latter typically at about its midpoint. Close to the infraorbital gland two or one are present. Approaching the temporal aspect of either lid, the ducts of both the infraorbital and exorbital lacrimal glands course within the lacrimal cord and usually merge. In some adult rats, when the eyelids are retracted laterally, it is evident that a crescentic fold of the palpebral conjunctiva contains a vertical pair of whitish, convex structures, the 'temporal canthal domes'. When present, one can serve as a marker for the duct orifice located close to the conjunctival fornix. Pseudostratified columnar epithelium lines the ducts from the orifice to the region of the infraorbital lacrimal gland. From the latter toward the exorbital lacrimal gland the epithelium may become pseudostratified cuboidal. That type exists close to and immediately within the exorbital gland. The variation in duct number within the lacrimal cord would have physiological consequences. By analogy with the circulatory system, it is expected that flow would occur more slowly within the multiple ducts in and near the exorbital lacrimal gland than in the one or two near the canthus. Where flow is slower, contact time of the secretion with the duct epithelium would be greater. Thus, modification of the lacrimal secretion is likely not to occur uniformly in the duct system but would take place primarily in and near the exorbital lacrimal gland rather than toward the duct orifice. PMID- 8500560 TI - Primary open-angle glaucoma alters retinal recovery from a thiobarbiturate: spatial frequency dependence. AB - Electrophysiological responses of the retina to a series of grating stimuli (6 768 min of arc/phase) were recorded in seven sessions using normal Beagles and in 21 sessions using Beagles afflicted with inherited glaucoma. A 15 degrees and a 30 degrees field, centered around the animal's area centralis, were used to stimulate the central retina. Two recording series were completed on each animal, with both stimulus sizes presented in each recording session. The first recording took place 30 min, and the second 2 hr, after the injection of thiamylal sodium. The signals recorded from the toroidal 15 degrees of the retina of the glaucomatous dogs during the second recording were significantly larger than those of the first recording. This difference was found only for the larger (> 48 min of arc/phase) gratings. No significant differences were found between the first and second recordings from the central 15 degrees of glaucomatous dogs, nor at any site in the normal dogs. PMID- 8500561 TI - N,N-dimethyladriamycin for treatment of experimental proliferative vitreoretinopathy: efficacy and toxicity on the rabbit retina. AB - N,N-Dimethyladriamycin (Me-2-ADM) derives from adriamycin (doxorubicin) by N methylation of its aminosugar moiety. In contrast to the parent agent, Me-2-ADM lacks mutagenicity and carcinogenicity. To evaluate its suitability for treatment of proliferative vitreoretinopathy (PVR), we studied the ability of Me-2-ADM to prevent traction retinal detachment in a model of PVR in rabbits. The model was created by intravitreal injection of 25,000 homologous dermal fibroblasts after vitreous gas compression. Two days after fibroblast injection, 5, 10 or 30 nmol Me-2-ADM was administered into the vitreous cavity. The control group received sham injections. All control eyes developed traction retinal detachments. Administration of 5 nmol Me-2-ADM slightly reduced the rate of retinal detachments to 90%. No retinal detachments occurred in the group treated with 10 nmol Me-2-ADM while 11% of eyes treated with 30 nmol Me-2-ADM developed retinal detachments. At day 28 of the study, light microscopic examination of retinas treated with 30 nmol Me-2-ADM revealed severe retinal damage while no such damage was present in eyes treated with 10 nmol. To exclude early retinal damage, 10 nmol Me-2-ADM were injected into eyes that had undergone vitreous gas compression but no fibroblast injection. On day 3, 7, and 14 after drug administration, ERGs were recorded simultaneously from drug treated and sham treated (contralateral) eyes. Light microscopy and transmission electron microscopy (TEM) were performed. Only transient ERG changes were observed at day 7, which recovered by day 14. All morphological findings in drug exposed eyes were in the range of normal when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500562 TI - Structure of the bovine transducin gamma subunit gene and analysis of promoter function in transgenic mice. AB - Transducin, the major photoreceptor guanine nucleotide-binding protein (G protein), is composed of three polypeptides: alpha, beta and gamma subunits. The transducin gamma subunit (T gamma) is expressed preferentially in photoreceptors. To study the control mechanisms for photoreceptor-specific expression of the T gamma gene, clones of the bovine T gamma gene were isolated from a bacteriophage genomic library, and the structure of the gene, including a portion of its 5' flanking region, was characterized. The gene consists of three exons and two introns. The first intron is 91 base pairs (bp) long and is located in the region corresponding to the 5'-untranslated sequence of the T gamma mRNA. The second intron is 5.3 kilobases (kb) long and splits the protein-coding region centrally. A bovine Alu-type repetitive sequence and putative Ret-1 and AP-1 binding site sequences are located in the 5'-flanking region. To investigate promoter function, 1.4 kb of DNA from the 5'-flanking region was joined to the prokaryotic chloramphenicol acetyltransferase (CAT) gene, and the chimeric bovine T gamma gene was used to generate a line of transgenic mice. CAT activity was readily detected in the retinas of the transgenic mice, but was absent in brain, heart, kidney, liver, lung, spleen and other tissues. These results suggest that the 1.4 kb 5'-flanking region of the bovine T gamma gene contains conserved sequence elements that direct tissue-specific expression. Human T gamma cDNA clones were characterized, and a short homologous region of the human T gamma gene promotor was obtained by polymerase chain reaction (PCR) amplification for comparison with the bovine promoter. PMID- 8500563 TI - Osmotic properties of the frog retinal pigment epithelium. AB - The water permeabilities of the membranes of the frog retinal pigment epithelial cells (RPE cells) were studied by means of double-barrelled, ion-selective microelectrodes. The cells were loaded with tetramethylammonium ion (TMA+) or with choline ions (Ch+) which served as intracellular volume markers. The intracellular activities of tetramethylammonium ions (TMAi+) and choline ions (Chi+) were measured with K+ selective intracellular microelectrodes. Intracellular activities of K+ and Cl- were also measured, and these ions were investigated as intracellular volume markers. The osmolarity on retinal side of the epithelium was changed abruptly. The rates of change in TMAi+ were linearly related to the changes in extracellular osmolarity in the range between (-46) (+46) mosmol l-1. The osmotic water permeability of the retinal membrane, Lp,r, estimated from these experiments was 3.8 x 10(-4) cm sec-1 (osmol l-1)-1. For an osmotic gradient of 23 mosmol l-1 there was no difference between Lp,r determined with Ch+, TMA+ and Cl- as intracellular volume markers. This rules out any specific biological artifacts of the volume measurement. Intracellular K+ was not suitable as intracellular volume marker, since the initial rates of change in the intracellular K+ activity were about 30% lower than the rates of change in TMAi+ when osmotic gradients less than +/- 46 mosmol l-1 were applied. Among the exogenous volume markers, TMA+ was found more reliable than Ch+. For osmotic gradients larger than 23 mosmol l-1 the volume change recorded with Ch+ was smaller than that recorded with TMA+ as volume marker. Since the membrane permeability for Ch+ was 23 times larger than for TMA+, this suggests that Ch+ left the cells during higher rates of shrinkage. The cells acted almost as ideal osmometers, since the steady-state changes in intracellular osmolarity closely reflected the retinal extracellular osmolarity changes. It is concluded that the osmotic water permeability of the retinal membrane is larger than that of the choroidal membrane. This suggests that the rate limiting step for osmotic water movements between the eye and the blood is the choroidal membrane of the retinal pigment epithelium. PMID- 8500564 TI - Photoreceptor degeneration and altered distribution of interphotoreceptor matrix proteoglycans in the mucopolysaccharidosis VII mouse. AB - Recent studies suggest that chondroitin sulfate proteoglycans in the retinal interphotoreceptor matrix (IPM) play a role in maintaining photoreceptor viability. We report herein studies on the retinas from mice with mucopolysaccharidosis type VII (MPS VII), a storage disorder resulting from virtual absence of beta-glucuronidase, an enzyme that is involved in the lysosomal degradation of chondroitin sulfate and other beta-glucuronide containing proteoglycans. The distribution of IPM chondroitin sulfate proteoglycans was examined by immunohistochemistry and lectin-based histochemistry, and compared with the morphology of photoreceptor and retinal pigmented epithelial (RPE) cells at various ages in MPS VII-affected mice. A number of lectins and antibodies were employed that react with epitopes of IPM chondroitin sulfate proteoglycans, including Triticum vulgaris agglutinin (WGA), Arachis hypogaea agglutinin (PNA), Phaseolus vulgaris agglutinin (PHA-L), and an antibody directed against chondroitin 6-sulfate (AC6S). In MPS VII-affected animals, slight shortening of photoreceptor outer segments occurs between postnatal months 1 and 8. This is associated with changes in the distribution of some of the IPM chondroitin sulfate proteoglycans and hypertrophy of the retinal pigmented epithelium due to the accumulation of cytoplasmic membrane-bounded vesicles. WGA- and PHA-L-, but not AC6S-binding glycoconjugates accumulate within the RPE of affected mice during this time. Immunoreactive chondroitin 6-sulfate is not observed within the RPE of affected animals, probably since the antibody employed does not label free chondroitin sulfate glycosaminoglycan fragments. A loss of the normal apical-basal distribution of chondroitin 6-sulfate and PHA-L binding IPM proteoglycans is apparent by 4 postnatal months. In contrast, WGA binding proteoglycan remains uniformly distributed through 8 months. Pyknotic photoreceptor nuclei are observed in months 2-5 and photoreceptor loss is observed by 6 months. Cone photoreceptor loss appears to occur prior to that of rod photoreceptors. These observations suggest that the absence of beta glucuronidase in the RPE of MPS VII mice may lead to an altered distribution of at least some IPM chondroitin sulfate proteoglycans. The resultant changes in the biochemical composition and/or physical structure of the IPM may affect subsequently its photoreceptor cell-supportive function leading to photoreceptor degeneration. PMID- 8500565 TI - Collagen type I mRNA levels in cultured human lamina cribrosa cells: effects of elevated hydrostatic pressure. AB - In primary open-angle glaucoma, elevated intraocular pressure is associated with distortion and reorganization of the connective tissue plates of the lamina cribrosa. We have previously postulated that the resident cells of the lamina cribrosa may respond to elevated intraocular pressure by altering the biosynthesis or degradation of extracellular matrix. To determine the response of lamina cribrosa cells to increased pressure, we have compared cultures of human lamina cribrosa cells, from five individuals, maintained under control and pressurized conditions in vitro. Cells from third to fifth passage cultures of human lamina cribrosa subjected to elevated hydrostatic pressure (50 mm Hg) for 7 days changed shape from flat and polygonal to elongated, synthesized and secreted increased amounts of collagen type I as shown by immunofluorescent localization, and exhibited increased mRNA levels of collagen type I (199 +/- 36% of control) (mean +/- S.D.), as determined by slot-blot hybridization. In contrast, beta actin mRNA levels were unchanged, indicating that the effects of elevated pressure are probably relatively selective. Our data indicate that elevated pressure increases the synthesis of collagen Type I by human lamina cribrosa cells in vitro. In vivo, lamina cribrosa cells may react to changes in their environment by modulating, specifically, changes in the mRNA levels, production, and secretion of extracellular matrix macromolecules. The relationship of these changes in extracellular matrix to those observed in glaucoma remains to be determined. PMID- 8500566 TI - Experimental autoimmune anterior uveitis (EAAU). III. Induction by immunization with purified uveal and skin melanins. AB - The pathogenicity of uveal tissue and melanin has been a controversial subject for a long time. The present new approach has elucidated some of the problems. Melanin granules have been extracted from bovine choroid, iris, hair and skin, and from human, monkey and rabbit choroid. The melanin granules have further been purified by detergent extractions, and are free from pathogenic retinal antigens. Lewis rats immunized with microgram doses bovine choroidal or iris melanin protein (in Freund's complete adjuvant or Hunter's adjuvant, combined with pertussis toxin) develop severe experimental autoimmune anterior uveitis (EAAU). No retinitis or pinealitis is found. The other melanins are weakly uveitogenic or inactive. The relative pathogenicity of the various melanins seems to be related to tissue and species specificity. The responsible hypothetic pathogenic structure UP-X (uveal pathogen X) is highly stable and resists proteolytic digestion by various enzymes. Its pathogenic activity is destroyed by hot 6 N HCl or longlasting 0.5 N NaOH treatment. In view of its chemical and immunological features it is probably identical to the pathogen PEP-X of bovine retinal pigment epithelial melanin. UP-X-induced EAAU can be transferred by spleen cells, and is suppressed by cyclosporin showing that a T-cell-mediated pathogenic mechanism predominates. It resembles human anterior uveitis by its specific location, its transient nature, and sparing of the retina. In these respects EAAU differs from retinal photoreceptor antigen-induced forms of EAU where retinitis with photoreceptor damage is a main feature. The involvement of melanin in human ocular diseases is discussed. PMID- 8500567 TI - Characterization of adenosine A2 receptors in bovine retinal membranes. AB - Two classes of extracellular receptors for adenosine, A1 and A2, have been demonstrated in the mammalian retina. Our laboratory has previously reported the pharmacological characteristics of the mammalian retinal A1 receptors. We now report our characterization of retinal A2 receptors based on data obtained from both adenylate cyclase assays and radioligand binding studies. [3H]-5'-N ethylcarboxamidoadenosine (NECA) in the presence of 10 nM cyclopentyladenosine (CPA, which selectively binds to A1 receptors) or [3H]-CGS 21680 were used to label the A2 binding sites. Using [3H]-NECA (plus CPA), two populations of binding sites, having Kds of 106 nM and 9.4 microM, were determined. [3H]-CGS 21680, a derivative of NECA which has been demonstrated to be highly selective for A2 receptors in brain synaptic membrane preparations was more potent than NECA at the higher affinity population of A2 sites, and saturation analysis revealed the presence of both a high affinity site, Kd of 18 nM, and a lower affinity site having a Kd of 4.3 microM. The high affinity site labeled by [3H] CGS 21680 corresponds to the A2a receptor. Using either radioligand, guanosine triphosphate-dependent shifts to a single population of binding sites were observed. Despite the differences in affinities revealed by the two radioligands for the high affinity A2 site, both [3H]-CGS 21680 and [3H]-NECA were competitively displaced by increasing concentrations of a variety of adenosine receptor agonists and antagonists, and exhibited an identical rank order of potency that is consistent with that reported for high affinity A2a receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500568 TI - Characterization of adenosine A2 receptors in bovine retinal pigment epithelial membranes. AB - The pharmacological characteristics of adenosine A2 receptors are described for membranes prepared from bovine retinal pigmented epithelial (RPE) cells. RPE cells were isolated after removal of retina, lysed by freeze-thawing, and membranes separated from cytoplasmic components. A single population of adenosine binding sites is present in RPE membranes, as determined from saturation analysis and competition binding assays. From Scatchard plots, this single class of binding sites exhibited low affinity for adenosine receptor agonists. These low affinity sites were labeled by [3H]-N-ethylcarboxamido-adenosine (NECA) or [3H] CGS 21680 and Kds of 423 and 5.3 microM were determined for each radioligand, respectively. NECA-mediated stimulation of adenylate cyclase demonstrated that these binding sites represent adenosine receptors. No high affinity A2a binding sites were detected in RPE membranes by either saturation studies, or by competition with adenosine A1-selective agonists which only displaced radioligand binding at high micromolecular concentrations. The low affinity A2 receptor on RPE differs from the high affinity A2a receptor characterized in bovine retinal membranes, but may be similar or identical to the lower affinity A2b receptor detected in retinal membranes as well as other tissues. PMID- 8500569 TI - Detection of ascorbic acid in the eye of the early chicken embryo by silver staining. AB - Ascorbate is found in high concentrations in the aqueous, lens and retina of a variety of animal species. Several functions have been proposed for this, including a vital role in aqueous secretion. We investigated the possible presence of ascorbate in the early embryonic chicken eye as a marker for the differentiation of the ciliary epithelium. Embryonic chicken eyes were processed for histochemical demonstration of ascorbate by silver staining. A strongly positive reaction was found in the interstitial matrix between the lens rudiment and the optic vesicle of the 2-day chicken embryo. By 3 days, with lens and optic cup separating from each other, the silver grains were concentrated in the vitreous cavity, primarily in a band-like configuration between the lens equator and the rim of the optic cup, which is the presumptive ciliary epithelium. A weaker reaction was seen in the lens vesicle and primitive neural retina. During the second and third day of incubation the optic vesicle is just beginning to expand. The appearance of ascorbic acid in the newly formed vitreous cavity at this time may indicate its importance in the biosynthesis of the matrix that is filling the expanding optic vesicle. PMID- 8500570 TI - Cloning of a human lacrimal lipocalin secreted in tears. PMID- 8500571 TI - Distribution of peripherin/rds mRNA in cone-dominant squirrel retina. PMID- 8500572 TI - Are crystallins designed for high intracellular stability? PMID- 8500573 TI - Fanconi anemia diagnosis and the diepoxybutane (DEB) test. PMID- 8500574 TI - Autologous transplant for CML revisited. AB - A chronic myelogenous leukemia (CML)-like disease can be induced in mice by infecting hematopoietic stem cells with a BCR/ABL-containing retrovirus; serial transplantation produces either normal or leukemic animals. In many patients with CML, autografting produces transient Philadelphia chromosome (Ph)-negativity, but Ph-negative hematopoiesis is prolonged in some cases. These and other observations suggest that at diagnosis, CML patients may have substantial numbers of normal stem cells in their marrow, which may in certain circumstances regain a proliferative advantage if leukemic hematopoiesis can be suppressed by intensive chemotherapy. Thus autografting may have the capacity to restore normal hematopoiesis for long periods in patients not eligible for treatment by allogeneic bone marrow transplantation. PMID- 8500575 TI - The role of lymphoid cells in hematopoietic regulation. AB - The present review has summarized evidence supporting the existence of different lymphoid subsets with opposing effects on hematopoietic cell growth (Table 1); specifically; a) growth stimulation resulting from the release of interleukins and granulocyte-macrophage colony-stimulating factor (GM-CSF) by particular subsets of lymphocytes and resting natural killer (NK) cells and b) growth inhibition resulting from the release of interferon (IFN) and tumor necrosis factor (TNF) by stimulated NK, B and lymphokine-activated killer (LAK) cells and inhibitory T lymphoid subsets. The systematic examination of the physiologic relevance of lymphoid subsets would add an important element to a more comprehensive model of hematopoietic regulation that might hold promise in future clinical applications. PMID- 8500576 TI - Characterization of an eosinophilic leukemia cell differentiation factor (ELDF) produced by a human T cell leukemia cell line, HIL-3. AB - An adult T cell leukemia cell line, HIL-3, constitutively secretes a factor which induces the phenotypical and functional eosinophilic differentiation of a human eosinophilic leukemia cell line, EoL-1. Biochemical characteristics of the factor, termed eosinophilic leukemia cell differentiation factor (ELDF), were examined. ELDF was precipitated by 35 to 65% saturated ammonium sulfate from the culture supernatants of HIL-3 cells (HIL-3 sup). ELDF was eluted in a peak corresponding to a molecular weight of 30 to 40 kd by gel filtration. Isoelectric focusing in the Rotofor showed that ELDF had isoelectric points of 5 to 6. ELDF was trypsin-sensitive and stable to heat treatment at 65 degrees C for 30 minutes but labile at 80 degrees C or pH lower than 3. Half of the activity adhered to lentil-lectin but not to Con-A, indicating that a part of ELDF is glycoprotein with an N-linked carbohydrate moiety, which did not seem to be essential for ELDF activity. The biochemical characteristics of ELDF and blocking experiments using cytokine-specific neutralizing antibodies suggest that ELDF is different from gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5) and interleukin-2 (IL-2), which may exist in HIL-3 sup, and that ELDF may be a previously unrecognized leukemia differentiation factor. PMID- 8500577 TI - Increased granulopoiesis after sequential administration of transforming growth factor-beta 1 and granulocyte-macrophage colony-stimulating factor. AB - Transforming growth factor-beta 1 (TGF-beta 1) is an inhibitor of the growth and differentiation of immature hematopoietic progenitors in vitro; however, we have demonstrated that TGF-beta 1 can promote granulopoiesis in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We therefore examined the effect of the combined administration of TGF-beta 1 and GM-CSF in vivo. First, TGF-beta 1 enhanced the specific binding of GM-CSF (2.0-fold) on bone marrow cells, reaching a maximum 40 hours after injection, while the specific binding of interleukin-3 (IL-3) was unaffected. Using GM-CSF-specific binding to determine the optimal regimen for cytokine administration in vivo, we found that the administration of TGF-beta 1 and GM-CSF in sequence increased myelopoiesis. Total numbers of colony-forming units-granulocyte/macrophage (CFU GM) and myeloblasts per femur were increased above the level obtained with the simultaneous injection of TGF-beta 1 plus GM-CSF, GM-CSF alone or TGF-beta 1 alone. Further, the sequential administration of TGF-beta 1 and GM-CSF resulted in enhanced numbers of mature granulocytes in both the bone marrow and peripheral blood. In contrast, the sequential combination of TGF-beta 1 and GM-CSF did not enhance the numbers or increase the recovery of erythroid cells in the bone marrow. These results show that TGF-beta 1 in vivo as in vitro has a multifunctional effect on bone marrow progenitors, and by using an optimal combination of TGF-beta 1 and GM-CSF in vivo, one can selectively increase both the central and peripheral granulopoietic compartments. PMID- 8500578 TI - MDS-like experimental myelodysplasia: multilineage abnormal hematopoiesis in transgenic mice harboring the SV40 large T antigen under an immunoglobulin enhancer. AB - The SV40 large T gene under the control of immunoglobulin enhancer induced hyperproliferation of multilineage hematopoiesis in transgenic mice. Huge splenomegaly was the major gross abnormality; mice were rather anemic, and neither leukoerythroblastosis nor invasion into tissues such as liver, kidneys or lymph nodes was common. In the latter phases of the disease, the proliferating cell type tended to shift to a variety of single-lineage hematopoiesis, but the majority of mice still showed the presence of multilineage hematopoiesis; such cells were somewhat dysplastic but low in neoplastic potential. A long-term observation by transplantation of the hematopoietic cells into lethally irradiated C57BL/6 mice resulted in a variety of neoplastic growths in the recipients; not only was myelodysplastic hypercellularity seen, but also single lineage hematopoietic malignancies such as B cell lymphomas/leukemias, histiocytic malignancies and even myeloid leukemias. The disease bore the proliferative feature solely in the spleen and bone marrow, and the transition from multilineage myelodysplasia into single-lineage hematopoiesis at some frequency is reminiscent of myelodysplastic syndromes (MDS) in humans. The results that the SV40 large T antigen was expressed in every proliferating cell, and that there was no apparent increase in any colony-stimulating cytokine(s), together with the results of the transplantation assays, suggested that the hyperproliferation of the hematopoietic cells was a direct consequence of the expression of SV40 large T antigen in these cells themselves. PMID- 8500579 TI - A cell-kinetics model for radiation-induced myelopoiesis. AB - A mathematical model of time-dependent cellular damage, repair, killing and repopulation of bone marrow following treatments with ionizing radiations is described. Effects from variable dose rates, multiple exposures, different radiation sources and arbitrary intervals between treatments can be modeled by ordinary differential equations. Of several unique features, the most unusual is that rate constants for injury, repair, killing and proliferation of cells are evaluated by likelihood analysis of animal mortality data. Results indicate that a relatively radioresistant pool of bone marrow cells mediates the proliferation of the hematopoietic stem cells. Applications include modeling of 1) myelopoietic integrity as a function of time and dose rate, 2) the whole-body survival curve (at any point in the treatment protocol) for cells critical to myelopoiesis, 3) a prompt dose equivalence from any completed portion of a therapeutic schedule and 4) potential gain from schedule changes during the course of the treatment. PMID- 8500580 TI - Are stem cells exposed to ionizing radiation in vivo as effective as nonirradiated transfused stem cells in restoring hematopoiesis? AB - Are the stem cells that survive graded doses of ionizing radiation as effective in restoring hematopoiesis in irradiated mice as transfused nonirradiated stem cells? This question was addressed by determining animal dose mortality and 10 day colony-forming units (CFU-S) survival curves and then replotting the percent animal survival against the number of CFU-S surviving the different doses of radiation, and by determining the number of nonirradiated CFU-S injected into fatally irradiated mice that result in a CFU-S dose mortality response curve. The number of CFU-S surviving per mouse after doses of radiation resulting in 95, 50 and 5% animal survival were calculated to be 520, 300 and 153, respectively. From the transfused CFU-S dose mortality curve of otherwise fatally irradiated mice (8.5 Gy), the number of transfused normal CFU-S required for 95, 50 and 5% animal survival was estimated to be 153, 24 and 3, respectively. The ratios of surviving CFU-S to nonirradiated, injected CFU-S are: at 95% survival (6.3 Gy), 3.4; at 50% survival (6.88 Gy), 12.5; and at 5% survival (7.4 Gy), 51.0. These data show that, in addition to a reduced number of CFU-S, as radiation dose increases, the quality of surviving CFU-S responsible for 30-day survival decreases. By implication, the long-term repopulating cell (LTRC) that is now known not to be the 10-day CFU-S must also decrease. PMID- 8500581 TI - Human Philadelphia chromosome-positive chronic myeloid leukemia: a potential model for antisense therapy. AB - We have developed an in vivo model of human chronic myeloid leukemia (CML). A peripheral blood (PB) sample of Philadelphia (Ph) chromosome-positive CML cells in lymphoid blast crisis was transplanted intravenously (IV) into sublethally irradiated severe combined immunodeficient (SCID) mice, and this resulted in engraftment with systemic proliferation. Growth of leukemia was monitored by PB cell morphology and by flow cytometric analysis of murine PB cells labelled with an anti-human leukocyte antigen (HLA) monoclonal antibody. Human cells were first detected in the PB at 4 weeks and comprised a mean of 57% of the total nucleated cells in the PB of these mice by 15 weeks. The Ph chromosome was retained and the population has been successfully passaged. BCR/ABL fusion gene expression was detected in a subsequent passage. Experiments are underway to use this in vivo model to assess the antileukemic activity of BCR/ABL antisense oligonucleotides. PMID- 8500582 TI - Dirofilaria immitis: effect of fluoromethyl ketone cysteine protease inhibitors on the third- to fourth-stage molt. AB - D. immitis third-stage larvae (L3) were cultured with fluoromethyl ketone cysteine protease inhibitors. By Day 5 in culture, none of the larvae cultured with 0.1, 0.2, 0.6, or 1.0 mM benzyloxycarbonyl-Phe-Ala-CH2F (Z-Phe-Ala-CH2F) has molted, while 63.2% of larvae in media without inhibitor had molted. At the two lower concentrations of inhibitor more larvae had initiated, but not completed, the molt. In addition to Z-Phe-Ala-CH2F, four other fluoromethyl ketone derivatives, Z-Phe-Arg-CH2F, amorpholine urea-(Mu)-Leu-Phe-CH2F, Mu-Tyr-Phe-CH2F, and Mu-Phe-Phe-CH2F, were tested to determine their effects on L3 in culture. All fluoromethyl ketones tested except Z-Phe-Arg-CH2F inhibited molting. Larvae cultured in inhibitors were determined to be alive as judged qualitatively by motility and quantitatively by reduction of 3-(4,5-diethylthiazol-2-yl)-2,5 diphenyltetrazolium. Electron microscopy demonstrated that L3 which were unable to molt after being cultured in a fluoromethyl ketone derivative had synthesized the new fourth-stage (L4) cuticle but had not shed the L3 cuticle. The same fluoromethyl ketone derivative that did not inhibit molting, Z-Phe-Arg-CH2F, was a slightly less effective inhibitor of larval extract-initiated hydrolysis of the synthetic peptide substrate, Z-Val-Leu-Arg-7-amino-4-methyl coumarin. L3 were also cultured through the molt in media containing the synthetic peptide substrate Z-Val-Leu-Arg-4- methoxy-B-naphthylamide to examine cysteine protease activity in situ. Fluorescence as seen on Days 0-4 during the molting process was first observed on the anterior tip of the larvae, and subsequently in the pharynx, with progression down the L4 as it shed the L3 cuticle. PMID- 8500583 TI - Entamoeba histolytica trophozoites: a surface-associated cysteine protease. AB - The purpose of this work was to define cell surface proteases on Entamoeba histolytica trophozoites. Molecular sizes of 2-mercaptoethanol-activated proteases were determined in several ameba cell fractions. Inhibited proteases were resolved in SDS-polyacrylamide gels and then defined by their ability to digest bovine albumin during electrophoretic migration of ameba bands through a stacking gel containing albumin. This second gel revealed nine gaps of digestion along the horizontal albumin line corresponding to proteases with molecular weights of 195, 175, 150, 124, 102, 70, 45, 36, and 28 kDa. The 70-kDa protease proved to be the most active in plasma membrane, in whole membrane fractions, and in total extracts of ameba. This protease appears to be an integral membrane component as it was reconstituted in an artificial membrane system in its active form, as well as because it was present on the surface of glutaraldehyde-fixed amebas. These results demonstrate that amebic trophozoites contain on their surface a very active protease, which may play a role in the digestion of host components. PMID- 8500584 TI - Trypanosoma vivax: evidence for only one RNA polymerase II largest subunit gene in a trypanosome which undergoes antigenic variation. AB - Previous studies suggested a correlation between antigenic variation in Kinetoplastida and the presence of two RNA polymerase (pol) II largest subunit genes in these organisms. We have found that Trypanosoma vivax, an African trypanosome which undergoes antigenic variation, is an exception, and has only one pol II largest subunit gene, indicating that probably neither of the two pol II genes found in other African trypanosomes is uniquely required for antigenic variation. PMID- 8500585 TI - Cytosolic free calcium in Plasmodium falciparum-infected erythrocytes and the effect of verapamil: a cytofluorimetric study. AB - The free Ca2+ ion concentration, measured by means of the fluorescent indicators Indo-1 and Fluo-3, has been compared in normal and parasitized erythrocytes from synchronized in vitro cultures of human blood infected with Plasmodium falciparum. The cells were loaded with the calcium probes in the form of their acetoxymethylesters. P. falciparum-infected red blood cells gradually accumulate more free Ca2+ ions than uninfected cells. The increased Ca2+ concentration is preferentially located inside a rather large central area, corresponding to the position and size of the parasite. In contrast, the Ca2+ concentration outside this area is not higher than that in normal red blood cells. This rise in calcium content becomes significant at the end of the ring stage. The concentration measured in 36-hr schizonts reaches two times that measured in uninfected erythrocytes, and it peaks to four times control values in 44-hr schizonts. The Ca2+ channel blocker verapamil (10 to 20 microM), added on the 24th hr of culture, slows down or blocks the parasite's growth at the trophozoite stage. However, the free Ca2+ concentration measured on infected red blood cells at different times after verapamil addition does not differ from that obtained in the absence of verapamil. These results demonstrate that the bulk of the free Ca2+ load of P. falciparum-infected erythrocytes is located inside the parasite or its parasitophorous vacuole. These data also indicate that the increased Ca2+ influx in P. falciparum-infected erythrocytes does not take the route of verapamil-sensitive Ca2+ channels. It also appears that the inhibitory effect of verapamil on the parasite's maturation does not depend on a change in its Ca2+ content. PMID- 8500586 TI - Schistosoma mansoni: identification and protective immunity of adult worm antigens recognized by T lymphocytes of outbred Swiss mice immunized with irradiated cercariae. AB - Percutaneous exposure of outbred Swiss mice to 500 Schistosoma mansoni (Egyptian strain) cercariae attenuated by 25,000 rad gamma radiation, twice at a 4-week interval, led to 80% protection against challenge with 100 live unattenuated cercariae compared to unimmunized control mice. The S. mansoni molecules that induce protective immunity in this model are not as yet identified. The capacity of an immunogen to induce efficient protective immunity depends largely on its T cell-activating potential, as T cells are required both for eliciting long lasting antibody formation and for antibody-independent cell-mediated immunity. To define such T cell antigen in S. mansoni, soluble adult worm antigens (SAWA) were separated by SDS-PAGE and electrotransferred onto nitrocellulose paper. Thirteen bands, identified by their M(r) were tested in T cell Western assays for their ability to stimulate proliferation of lymph node cells from 23 mice immunized with irradiated cercariae for the second time 2-5 weeks earlier. Lymphocytes from all mice responded to only a few (maximum of 6) bands. The response rate for the 13 SAWA bands tested ranged from 0-43%. These findings suggest a heterogeneity in T cell responses of individual mice to each of the SAWA bands and have implications that should be considered in the selection of immunogens to be assayed for anti-Schistosomiasis mansoni protective capacity. A highly significant protection against S. mansoni challenge in outbred Swiss mice was obtained exclusively following vaccination with a cocktail of soluble adult worm T cell immunogens that are recognized by 30-40% of individuals. PMID- 8500587 TI - The divergence of Trichomonas vaginalis virus RNAs among various isolates of Trichomonas vaginalis. AB - Trichomonas vaginalis virus is a double-stranded (ds) RNA virus found in the parasitic protozoan T. vaginalis. To examine the possible existence of related viruses in various T. vaginalis strains and isolates, we screened 20 such isolates and found the characteristic 5.5-kb viral ds RNA in 16 of them. An additional 0.5-kb ds RNA band was also identified in 10 of these virus-infected T. vaginalis isolates. In a local isolate T1, this 0.5-kb ds RNA cross-hybridized with the 5.5-kb ds RNA. Preliminary evidence from CsCl buoyant density gradient centrifugations suggests that the two ds RNA species are encapsidated in separate viral particles by the same capsid protein. The 5.5-kb ds RNA in isolate T1 exhibited moderate hybridization with the prototype 5.5-kb ds RNA in T. vaginalis stratin NIH-Cl. Little cross-hybridization was observed among the 5.5-kb ds RNAs from T. vaginalis isolates JH32A No. 4, T1 and T5, although the viral proteins in these isolates are of similar molecular weight and share common epitopes as viewed by Western blotting. Hybridization characteristics of the 5.5-kb ds RNAs in individual isolates were further analyzed, and the results suggest great ds RNA divergence among the T. vaginalis viruses. Interestingly, the 0.5-kb ds RNA in different isolates of T. vaginalis also exhibited divergence in patterns closely associated with that of the 5.5-kb ds RNA. PMID- 8500588 TI - Wuchereria bancrofti: freeze-fracture study of the epicuticle of microfilariae. AB - The freeze-fracture technique was used to analyze the surface of microfilariae of Wuchereria bancrofti. The examination of thin sections showed that the epicuticle is formed by two closely apposed membrane-like structures, appearing as hepta laminated structures. Freeze-fracture replicas revealed the presence of two fracture faces. The outer one is smooth but presents rosette-like structures. The inner face, which is in contact with the hypodermal cells, presents a large number of particles. PMID- 8500589 TI - Identification of mRNA-binding proteins of the lower trypanosomatid Leptomonas collosoma. PMID- 8500590 TI - Plasmodium chabaudi: a short-term in vitro culture method and its application to chloroquine resistance testing. PMID- 8500591 TI - Plasmodium falciparum: a molecular view of protein transport from the parasite into the host erythrocyte. PMID- 8500592 TI - A brief history of proteoglycans. PMID- 8500594 TI - Molecular cloning and analysis of the protein modules of aggrecans. AB - The large aggregating chondroitin sulfate proteoglycan of cartilage, aggrecan, has served as a prototype of proteoglycan structure. Molecular cloning has elucidated its primary structure and revealed both known and unknown domains. To date the complete structures of chicken, rat and human aggrecans have been deduced, while partial sequences have been reported for bovine aggrecan. A related proteoglycan, human versican, has also been cloned and sequenced. Both aggrecan and versican have two lectin domains, one at the amino-terminus which binds hyaluronic acid and one at the carboxyl-terminus whose physiological ligand is unknown. Both lectins have homologous counterparts in other types of proteins. Within the aggrecans the keratan sulfate domain may be variably present and also has a prominent repeat in some species. The chondroitin sulfate domain has three distinct regions which vary in their prominence in different species. The complex molecular structure of aggrecans is consistent with the concept of exon shuffling and aggrecans serve as suitable prototypes for comprehending the evolution of multi-domain proteins. PMID- 8500593 TI - Isolation and purification of proteoglycans. AB - Purification of a protein typically involves development of a quantitative assay to track protein integrity (e.g. enzyme activity) during subsequent isolation steps. The generalized procedure involves choosing the source of the protein, defining extraction conditions, developing bulk purification methods followed by refined, more selective methods. The purification of proteoglycans is often complicated by a) limited source quantities, b) necessity of chaotropic solvents for efficient extraction, c) their large molecular size and d) lack of defined functions to enable purity (i.e. activity, conformation) to be assessed. Because the usual goal of proteoglycan purification is physical characterization (intact molecular weight, core protein and glycosaminoglycan class and size), the problems of a suitable assay and/or native conformation are avoided. The 'assay' for tracking proteoglycan isolation typically utilizes uronic acid content or radiolabel incorporation as a marker. Once extracted from their cellular/extracellular environment, proteoglycans can be isolated by density gradient centrifugation and/or column chromatography techniques. Recent advances in the composition of chromatographic supports have enabled the application of ion-exchange, gel permeation, hydrophobic interaction and affinity chromatography resins using efficient high-pressure liquid chromatography to proteoglycan purification. PMID- 8500595 TI - The link proteins. AB - Aggregates of chondroitin-keratan sulfate proteoglycan (aggrecan) and hyaluronic acid (hyaluronan) are the major space-filling components of cartilage. A glycoprotein, link protein (LP; 40-48 kDa) stabilizes the aggregate by binding to both hyaluronic acid and aggrecan. In the absence of LP, aggregates are smaller (as estimated by rotary shadowing of electron micrographs) and less stable (they dissociate at pH 5) than they are in the presence of LP. The proteoglycan aggregate, including LP, is dissociated in the presence of chaotropes such as 4 M guanidine hydrochloride. On removal of the chaotrope, the complex will reassociate. This forms the basis of the isolation of LP from cartilage and has been described in detail elsewhere. Tryptic digestion of the proteoglycan aggregates results in a high molecular weight product that consists of hyaluronic acid to which is bound LP and the N-terminal globular domain of aggrecan (hyaluronic acid binding region; HABR) in a 1:1 stoichiometry. The amino acid sequences of LP and HABR are surprisingly similar. The amino acid sequence can be divided into three domains; an N-terminal domain that falls into the immunoglobulin super-family and two C-terminal domains that are similar to each other. The DNA structure echoes this similarity, in that the major domains are reflected in three separate exons in both LP and HABR. The two C-terminal domains are largely responsible for the association with HA and are related to two recently described hyaluronate-binding proteins, CD44 and TSG-6. A variety of approaches, including analysis of the forms of LP found in vivo, rotary shadowing and analysis of the sequence in the immunoglobulin-like domain, have shed considerable light on the structure-function relationships of LP. This review describes the structure and function of LP in detail, focusing on what can be inferred from the similarity of LP, HABR and related molecules such as immunoglobulins and lymphocyte HA-receptors. PMID- 8500596 TI - Small proteoglycans. AB - In this review the structure and functions of two non-related proteoglycan families are discussed. One family represents a group of extracellular matrix macromolecules characterized by core proteins with leucine-rich repeat motifs. Within this family special attention is given to those members which carry chondroitin or dermatan sulfate glycosaminoglycan chains. The second family is characterized by repeat sequences of serine and glycine. Their members are products of a single core protein gene and are characteristic constituents of secretory vesicles in cells of the haematopoietic lineage. PMID- 8500597 TI - Proteoglycans of basement membranes. AB - Proteoglycans carrying either heparan sulfate and/or chondroitin sulfate side chains are typical constituents of basement membranes. The most prominent proteoglycan (perlecan) consists of a 400-500 kDa core protein and three heparan sulfate chains. Electron microscopy and cDNA sequencing show a complex and elongated domain structure for the core protein which in part is homologous to that of the laminin A chain. This structure may be varied by alternative splicing and proteolysis. Integration into basement membranes probably occurs by heparan sulfate binding to laminin and collagen IV, core protein binding to nidogen and by limited self assembly. The proteoglycan is in addition a cell-adhesive protein which is recognized by beta 1 integrins. Several more proteoglycans with smaller core proteins (10-160 kDa) apparently exist in basement membranes but are less well characterized. Biological functions include control of filtration through basement membranes and binding of growth factors and protease inhibitors. PMID- 8500598 TI - Nervous tissue proteoglycans. AB - The structure, biosynthesis, localization, and possible functional roles of nervous tissue glycosaminoglycans and proteoglycans were last reviewed several years ago. Since that time, there has been an exponential increase in publications on the neurobiology of proteoglycans. This review will therefore focus on reports which have appeared in the period after 1988, and especially on those concerning the properties of individual characterized nervous tissue proteoglycans. Related areas such as the regulation of glycosaminoglycan biosynthesis and the roles of cell surface proteoglycans in adhesion and growth control are covered in other contributions to this special topic issue. PMID- 8500599 TI - Altered proteoglycan gene expression and the tumor stroma. AB - Tumor stroma is a specialized form of tissue that is associated with epithelial neoplasms. Recent evidence indicates that significant changes in proteoglycan content occur in the tumor stroma and that these alterations could support tumor progression and invasion as well as tumor growth. Our main hypothesis is that the generation of tumor stroma is under direct control of the neoplastic cells and that, via a feedback loop, altered proteoglycan gene expression would influence the behavior of tumor cells. In this review, we will focus primarily on the work from our laboratory related to the altered expression of chondroitin sulfate proteoglycan and its role in tumor development and progression. The connective tissue stroma of human colon cancer is enriched in chondroitin sulfate and the stromal cell elements, primarily colon fibroblasts and smooth muscle cells, are responsible for this biosynthetic increase. These changes can be reproduced in vitro by using either tumor metabolites or co-cultures of human colon carcinoma cells and colon mesenchymal cells. The levels of decorin, a leucine-rich proteoglycan involved in the regulation of matrix assembly and cell proliferation, are markedly elevated in the stroma of colon carcinoma. These changes correlate with a marked increase in decorin mRNA levels and a concurrent hypomethylation of decorin gene, a DNA alteration associated with enhanced gene expression. Elucidation of decorin gene structure has revealed an unexpected degree of complexity in the 5' untranslated region of the gene with two leader exons that are alternatively spliced to the second coding exon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500601 TI - Characterization of adenosine deaminase (ADA)-negative B-lymphoblastoid cells cocultured with ADA-positive fibroblasts. AB - A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 mumol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 x 10(5) and 1 x 10(6) cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA negative cells proliferated well when the ratio of ADA-positive cells/ADA negative cells was over 1/10. PMID- 8500602 TI - Circadian variation in serum cortisol and circulating neutrophils are markers for circadian variation of bone marrow proliferation in cancer patients. AB - Serum cortisol, circulating white blood cells and DNA cell cycle distribution in bone marrow cells were measured during daytime (11.00) and at midnight (24.00) over single 24-hour periods in 15 cancer patients. The neutrophils and fraction of bone marrow cells in S-phase showed the same circadian variation as cortisol with higher values in daytime as compared to midnight in 11 patients with a normal cortisol rhythm (p < 0.05). The lymphocytes, eosinophils and basophils all had significantly higher values at midnight as compared to daytime. There were significant correlations between cortisol and neutrophils, lymphocytes, eosinophils and basophils. The correlation between neutrophils and fractions of bone marrow cells in S-phase and S + G2/M-phase were highly significant (r = 0.74, p = 0.0001 and r = 0.72, p = 0.0001, respectively). In 8 of 13 patients (61.5%) without bone marrow infiltration both cortisol and neutrophils showed identical circadian variation as bone marrow cells in S-phase and S + G2/M-phase. Furthermore, for the total series a significant correlation between S-phase, cortisol and neutrophils was found by multiple regression analysis (p < 0.0001). These findings strengthen the possibility of using the circadian variation in cortisol and neutrophils as marker rhythms for circadian variation in bone marrow proliferation, thus allowing optimization of cytotoxic therapy and individualization of chronotherapy. PMID- 8500600 TI - Cytokines and proteoglycans. AB - Cytokines play an important regulatory role in the metabolism of proteoglycans. Proteoglycans are found in plasma membranes, but predominantly in the extra cellular matrix. In the latter they are quantitatively and qualitatively essential components. Especially in a tissue like cartilage without any blood vessels, the cells are dependent on cytokines for the communication among themselves in the extra-cellular matrix and also for communication with the 'outside world'. Various cytokines have been found to be able to penetrate the extra-cellular matrix and inhibit, respectively stimulate the proteoglycan synthesis. Also, the degradation of proteoglycans can be stimulated, respectively inhibited by several cytokines. In addition, some cytokines have been found which regulate the effects of the other cytokines. With respect to proteoglycan metabolism a complex cytokine network is emerging. Furthermore it is becoming increasingly clear that proteoglycans are connected to the cytokine network by their own bioactive functions. First, they possibly possess cytokine activities themselves. Second, they can function as receptors, protectors, inactivators and storage ligands for cytokines. So the proteoglycans are clearly involved in the feedback signalling from the extra-cellular matrix to the cells that are synthesizing this extra-cellular matrix. Together with agonistic or antagonistic cytokines they are involved in the regulation of proteoglycan turnover during balanced or unbalanced metabolism in normal, respectively pathological situations. PMID- 8500603 TI - Observations on two members of the Swedish family with congenital dyserythropoietic anaemia, type III. AB - Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28c (1c = haploid DNA content) and 48c respectively, and some DNA synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with 3H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins Dolichos biflorus and Ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents. PMID- 8500604 TI - Mononuclear cells from peripheral blood of untreated hairy-cell leukaemia patients enhance the growth of BFU-e. AB - To further characterise the regulation of haematopoiesis in hairy-cell leukaemia (HCL), we investigated the effect of mononuclear cells from peripheral blood (PBMNC) of untreated HCL patients on the in vitro growth of BFU-e. The effect was tested in an autologous system employing post-treatment HCL PBMNC, and in an allogeneic system. A significant enhancing effect of the pre-treatment HCL PBMNC was seen. In contrast to studies by others, IFN-alpha consistently inhibited the growth of BFU-e from normal donors, from pre- and post-treatment HCL PBMNC, and mixtures thereof. Since PBMNC from patients with very high percentages of circulating hairy cells (HC) also had an enhancing effect, HC was a likely source of one or more enhancing factors. Thus, even though we cannot exclude a minor inhibitory activity of the HC by our assay, their net effect seems to be enhancing, and therefore it seems unlikely that the HC is directly responsible for the anaemia in HCL. PMID- 8500605 TI - Metabolic evidence of cobalamin deficiency in bone marrow cells harvested for transplantation from donors given nitrous oxide. AB - Nitrous oxide inactivates cobalamin, but clinically apparent sequelae ensue in nondeficient individuals only when exposure is prolonged. The gas is widely used in anesthesia, therefore, and is commonly given to donors during harvesting of their bone marrow cells for transplantation. The present study shows that nitrous oxide administered for only 75-120 minutes induced mild but unequivocal DNA synthetic abnormalities attributable to cobalamin deficiency in the harvested marrow cells of 4 out of 5 donors; the deoxyuridine suppression test in these 4 patients showed abnormal results more than 4 standard deviations above the reference mean. Metabolic evidence of cobalamin deficiency in cryopreserved cells diminished only slightly when they were thawed and retested 1 day later, but was no longer detectable in cells thawed and tested on the 3rd day. In contrast, cells harvested under nitrous oxide-free anesthesia in 4 subjects showed no evidence of cobalamin deficiency in the deoxyuridine suppression test. These results demonstrate that even relatively brief exposure to nitrous oxide induces cobalamin deficiency in harvested bone marrow cells, and that the cells remain metabolically impaired for more than 24 hours. Although clinical sequelae are not apparent at this time, the several potential implications of our findings indicate that the use of nitrous oxide in bone marrow transplantation needs to be evaluated further. PMID- 8500606 TI - Phospholipid determination in platelets, plasma and red cells of patients with chronic myeloproliferative disorders. AB - Red cell phospholipids (PLs) were assessed in 11 patients with essential thrombocythemia and 5 patients with polycythemia vera. Platelet and plasma PLs were also determined in 10 of these patients, and the results were compared with studies performed in 16 healthy volunteers. The amount of platelet PLs in patients was similar to controls (556 +/- 90 mmol/10(9) cells, versus 481 +/- 91 mmol/10(9) cells), as was the percentage of the main specimens of these compounds, including phosphatidylserine (11.1 +/- 0.8%), which is relevant for platelet procoagulant activity. We did not find differences between red cell PLs of patients (300 +/- 60 nmol/10(9) cells), versus controls (289 +/- 71 nmol/10(9) cells), and the sphingomyelin/phosphatidylcholine ratio in these cells was the same in both groups (0.75 +/- 0.1). Finally, we did not detect any alteration in the amount of plasma PLs specimens. PMID- 8500607 TI - Salting-out procedure for isolation of DNA from stored bone marrow slides for PCR. PMID- 8500608 TI - Thrombocytopenia (TP) in HIV infection. PMID- 8500609 TI - Cutaneous lymphoma with symmetrical onset. PMID- 8500610 TI - The cis/trans interconversion of the calcium regulating hormone calcitonin is catalyzed by cyclophilin. AB - The cytosolic peptidyl-prolyl cis/trans isomerase cyclophilin from pig kidney can accelerate catalytically the cis/trans isomerization of prolyl peptide bonds. One and two-dimensional 1H NMR spectroscopy was used to prove that the polypeptide hormone calcitonin is a substrate for cyclophilin. Isomerization of only one of the two prolyl peptide bonds is catalyzed significantly. The efficiency of catalysis was calculated by lineshape analysis and NOESY spectroscopy. Cyclosporin A completely blocks the effect of the enzyme on the conformational dynamics of the polypeptide. PMID- 8500611 TI - Carboxyl group hydrogen bonding in X-ray protein structures analysed using neutron studies on amino acids. AB - A method is proposed to make a distinction between ionized and neutral carboxyl groups in X-ray protein structures. This is based on an analysis of the relative hydrogen bonding populations and bond-length bond-valence correlations in high precision neutron studies of amino acids and small peptides. With the help of this method, four amino acid residues containing carboxyl groups in the refined structure of triclinic hen egg-white lysozyme have been analysed. Two of these, Glu-35 and Asp-52, are involved in lysozyme function, while the other two, Glu-7 and Asp-101, form a protein-protein inter-molecular contact in the triclinic structure. PMID- 8500612 TI - Bile salt-stimulated lipase in human milk. Evidence that bile salt induces lipid binding and activation via binding to different sites. AB - Human milk bile salt-stimulated lipase ensures efficient triacylglycerol utilization in breast-fed newborns. For activity against long-chain triacylglycerol, primary bile salts are a prerequisite. Bile salts also protect the enzyme from inactivation by intestinal proteases. We have studied the effect of different bile salts on activation, protease protection, lipid binding, and enzyme inactivation, caused by an arginine modifying agent. Based on the results we propose a model involving two bile salt binding sites; one activation-site specific for primary bile salt, and another, less specific, lipid binding promoting site at which also secondary bile salt binds. Binding to this latter site induces binding of enzyme to emulsified substrates but binding promoting site at which also secondary bile salt binds. Binding to this latter site induces binding of enzyme to emulsified substrates but without subsequent lipolysis. PMID- 8500613 TI - Production of biologically active light chain of tetanus toxin in Escherichia coli. Evidence for the importance of the C-terminal 16 amino acids for full biological activity. AB - The activity of the light (L) chain of tetanus toxin, and of mutants constructed by site-directed mutagenesis, was studied by expression and purification of the proteins from E. coli. Wild-type recombinant L chain (pTet87) was active in the inhibition of exocytosis from cultured bovine adrenal chromaffin cells, although at a level 5-15% of that of L chain purified from tetanus toxin. L chain mutants which terminated at Leu-438 (pTet89), or which contained a Cys-to-Ser mutation at residue 439 (pTet88) were equally as active as the full-length recombinant protein. The reduced activity of pTet87 L chain correlated with C-terminal proteolysis of the protein upon purification. A tryptic fragment derived from native light chain and which terminated at Leu-434 also showed reduced activity in the exocytosis assay, consistent with a requirement of the C-terminal region of the L chain for maximal activity. pTet87 L chain, but neither of the mutants, could be associated with purified H (heavy) chain to form a covalent dimer which induced the symptoms of tetanus in mice. The ability to form biologically active toxin using recombinant L chain will be of great value in structure-function studies of tetanus toxin. PMID- 8500614 TI - A synthetic peptide mimics troponin I function in the calcium-dependent regulation of muscle contraction. AB - A new technique for treating skinned cardiac muscle fibers has been developed in which troponin I is extracted, giving rise to unregulated fibers. The effect of the 12-residue troponin I peptide on these fibers indicates that this region of troponin I is solely responsible for muscle relaxation (inhibition of force). Furthermore, troponin I peptide-troponin C reconstituted fibers are stable through several contraction-relaxation cycles indicating the peptide can switch binding sites between actin and troponin C. The troponin I peptide can substitute for the native protein as part of the calcium-sensitive molecular switch that controls muscle regulation. PMID- 8500615 TI - Calcium dependent activation of the NF-AT transcription factor by p59fyn. AB - A reporter gene under the control of a T-cell antigen receptor element was activated in Jurkat cells by antigen receptor triggering or by a combination of phorbol myristate acetate, which activates protein kinase C, and a calcium ionophore. Both these signals were necessary for expression of the reporter gene. When co-transfected with a construct capable of overexpressing the tyrosine kinase p59fyn, the reporter gene was activated by PMA alone. Thus p59fyn could replace the calcium ionophore but not activation of protein kinase C. The activation by p59fyn plus PMA was blocked by EGTA and by the immunosuppressant drug cyclosporin A. PMID- 8500616 TI - Conformational changes of the alpha 1-proteinase inhibitor affecting its cholesterol binding ability. AB - The effect of conformational changes of the alpha 1-proteinase inhibitor (alpha 1PI) on alpha 1PI-cholesterol complex (1:2 mol/mol) formation in vitro was studied with electrophoretic and gel chromatographic methods. Native alpha 1PI was modified by adding free thiol agents such as glutathione, cysteine HCl, or DL homocysteine, by heating, or by cleavage with pancreatic elastase or trypsin. Conformational changes of the alpha 1PI molecule induced by these procedures were all accompanied by a loss of its ability to bind cholesterol in vitro under standard experimental conditions. The data suggest alpha 1PI-cholesterol binding to be affected by both direct and indirect modifications of the alpha 1PI reactive center, that is situated on a mobile peptide loop. PMID- 8500617 TI - Mobility in pyruvate dehydrogenase complexes with multiple lipoyl domains. AB - High-field NMR studies were carried out with genetically-reconstructed pyruvate dehydrogenase (PDH) complexes of Escherichia coli containing from zero to nine lipoyl domains per lipoate acetyltransferase (E2p) subunit. The only significant differences between the NMR spectra were the increasing intensities of the signals derived from the lipoyl domains and their associated linkers, and the much enhanced signal from the E3-binding domain and its linker in complexes that are devoid of lipoyl domains. The results suggest an explanation for the presence of three lipoyl domains per E2p subunit in the wild-type PDH complex, based on its greater inherent mobility, and potentially more efficient active-site coupling, than any of the other complexes. PMID- 8500618 TI - Molecular characterization of the red visual pigment gene of the American chameleon (Anolis carolinensis). AB - The red sensitive visual pigment of the American chameleon, Anolis carolinensis, is unique in having absorption maximum some 50 nm further into the red than any other terrestrial vertebrate examined. We report here the isolation and sequence determination of the genomic DNA clone for the Anolis red visual pigment gene. Phylogenetic analysis shows that this gene is most closely related to the gecko green and chicken red visual pigment genes. We identified nine Anolis-specific amino acid replacements, seven of which reside in transmembrane domains and might contribute to the red-shift of the Anolis visual pigments. PMID- 8500619 TI - Folding topology and DNA binding of the N-terminal fragment of Ada protein. AB - Three amino terminal fragments of Escherichia coli Ada protein (39 kDa) with different molecular masses (14 kDa, 16 kDa and 20 kDa) were prepared in large quantities from an E. coli strain harboring plasmids constructed for the overproduction of the truncated proteins. The three fragments can be methylated to an extent similar to that of the intact molecule. The methylated 16 kDa fragment specifically binds to the ada box on a DNA duplex. NMR analyses revealed that the 14 kDa fragment comprises two alpha-helices and a beta-sheet with parallel and anti-parallel mixed strands. A comparison of the 15N-1H HMQC spectra of the fragments has led to the conclusion that this tertiary structure within the 14 kDa fragment is retained in the larger 16 kDa and 20 kDa fragments. PMID- 8500620 TI - Prediction of a novel topology in the N-terminal, 14 kDa fragment of Ada protein. AB - Previously determined protein structures have been analysed, in order to find folding motifs similar to that proposed by NMR spectroscopy, for the N-terminal, 14 kDa fragment of the Ada protein. The analyses reveal only limited similarities with the NMR-derived structural data and strongly suggest that this region of the Ada protein adopts a previously unobserved topology. Characteristic structural features, which arise from the inferred chain connectivity, are examined through comparisons with other structures. Using this information, the topology of the Ada protein 14 kDa fragment has been predicted in order to provide structural data not yet attainable from NMR experiments. PMID- 8500621 TI - Non-covalent binding of the heavy atom compound [Au(CN)2]- at the halide binding site of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. AB - The Na[Au(CN)2] heavy atom derivative contributed considerably to the successful elucidation of the crystal structure of haloalkane dehalogenase isolated from Xanthobacter autotrophicus GJ10. The gold cyanide was located in an internal cavity of the enzyme, which also contains the catalytic residues. Refinement of the dehalogenase-gold cyanide complex at 0.25 nm to an R-factor of 16.7% demonstrates that the heavy atom molecule binds non-covalently between two tryptophan residues pointing into the active site cavity. At this same site also chloride ions can be bound. Therefore, inhibition of dehalogenase activity by the Au(CN)-2 presumably occurs by competition for the same binding site as substrates. PMID- 8500622 TI - Post-translational processing and Thr-206 are required for glycosylasparaginase activity. AB - Lysosomal glycosylasparaginase is encoded as a 36.5 kDa polypeptide that is post translationally processed to subunits of 19.5 kDa (heavy) and 15 kDa (light). Recombinant glycosylasparaginase has been expressed in Spodoptera frugiperda insect cells enabling the precursor and processed forms to be isolated and their catalytic potential determined. Only the subunit conformation was functional indicating glycosylasparaginase is encoded as an inactive zymogen. The newly created amino terminal residue of the light subunit following maturation, Thr 206, is believed to be involved in the catalytic mechanism [1992, J. Biol. Chem. 267, 6855-6858]. Here we have constructed two amino acid substitution mutants replacing Thr-206 with Ala-206 or Ser-206 and demonstrate that both destroy enzyme activity. PMID- 8500623 TI - Peptide sequencing identifies MSS1, a modulator of HIV Tat-mediated transactivation, as subunit 7 of the 26 S protease. AB - Subunit 7 is an integral component of the human erythrocyte 26 S protease. Peptide sequence analysis reveals that 22 amino acids from the N-terminus of subunit 7 correspond exactly to the N-terminus of MSS1, a modulator of HIV gene expression. Additional internal peptides from subunit 7 obtained by CNBr cleavage also match 100% with the deduced amino acid sequence of MSS1. Based on the fact that directly sequenced peptides from subunit 7 are identical to more than 12% of the hypothetical translation product of MSS1, and the fact that the molecular weight of subunit 7 (49 kDa) corresponds to the predicted molecular weight of MSS1 (48,633 Da), we conclude that subunit 7 is MSS1. PMID- 8500624 TI - Evolutionary relationships between yeast and bacterial homoserine dehydrogenases. AB - The Saccharomyces cerevisiae HOM6 gene, encoding homoserine dehydrogenase (EC 1.1.1.3) was cloned and its nucleotide sequence determined. The yeast homoserine dehydrogenase shows extensive homology to the homoserine dehydrogenase domains of the two aspartokinase-homoserine dehydrogenases from Escherichia coli as well as to the homoserine dehydrogenases from Gram positive bacteria. Sequence alignment reveals that the yeast enzyme is the smallest homoserine dehydrogenase known, owing to the absence of a C-terminal domain endowed with the L-threonine allosteric response in Gram positive bacteria. Accordingly, the S. cerevisiae enzyme appears to be a naturally occurring feedback resistant homoserine dehydrogenase. Our results indicate that homoserine dehydrogenase was originally an unregulated enzyme and that feedback control acquisition occurred twice during evolution after the divergence between Gram positive and Gram negative bacteria. PMID- 8500625 TI - Influence of liver environment on the maturation of isolated epiphyseal chondrocyte transplants. AB - To study the phenomenon of chondrocyte hypertrophy, rat or mouse isolated epiphyseal chondrocytes were transplanted into the kidney, spleen or liver for 7 days. Each transplant had its own control transplanted intramuscularly. Rat chondrocytes were also placed on a chorioallantoic membrane of chick embryos, incubated for 11 days and transferred for the next 11 days either onto another chorioallantoic membrane or into rat muscle. The surface area of largest lacunae cross-sections in cartilage produced by transplants was measured as an indicator of chondrocyte hypertrophy. In cartilage from the chorioallantoic membrane chondrocytes remained small but hypertrophied after transfer into a muscle. Lacunae in seven-day-old cartilage nodules in the liver were considerably larger than in muscle, kidney or spleen. After 7 days matrix calcification was observed only in liver transplants. Thus, liver environment, stimulated chondrocyte hypertrophy. Taken together these results suggest that chondrocytes are unable to hypertrophy spontaneously and that the rate of hypertrophy is subjected to regulation by extra-cartilaginous factor(s). PMID- 8500626 TI - Changes in the distribution of blood vessels in the rat cerebral hemisphere injured during early postnatal period. AB - A response of the vascular network of rat cerebral hemisphere to injury inflicted neonatally and on the postnatal day 6 was examined. After the neonatal injury, no change could be recorded, however, following similar lesion made in 6-day-old rats zones of significantly increased vascular density were observed. The data indicate a significant change in the reactivity of cerebral blood vessels to injury occurring during the earliest period of postnatal development. This phenomenon is considered to be parallel to a similar developmental increase in the ability of astroglia to form a reactive gliosis. PMID- 8500627 TI - Ehrlich ascites tumour cell spreading is induced upon contact with immobilized isolated fibroblast plasma membranes and fibronectin. AB - Ehrlich ascites tumour (EAT) cells normally growing in suspension, adhere and spread upon contact with fibroblasts. Changes in EAT cell morphology and adhesiveness induced in contact with purified fibroblast plasma membranes, fibroblast extracellular matrix and fibronectin were investigated. EAT cells adhered readily to glass covered with fibroblast extracellular matrix or fibronectin, but they did not spread. Immobilization of fibroblast plasma membranes or fibronectin on nitrocellulose restored EAT cell ability to spread. Tumour cells spread on immobilized plasma membranes or fibronectin maintained a "fried egg" morphology, while these spread on living fibroblasts were rather elongated. EAT cells preincubated with anti-fibronectin serum lost their ability to adhere to any of the tested substrata: living and fixed fibroblasts, fibroblast extracellular matrix, nitrocellulose with immobilized fibroblast plasma membranes or fibronectin. When anti-fibronectin serum was applied only to these substrata and it was washed out before EAT cell plating, EAT cell adhesion and spreading were not significantly changed. Extraction of extracellular matrix components from immobilized fibroblast plasma membranes did not influence EAT adhesion and spreading. The results are discussed with reference to the specific role of fibronectin in the growth of EAT cells as a solid tumour or suspension. PMID- 8500628 TI - Addition of iron and zinc complexes to Eagle's Minimal Essential Medium is sufficient to induce and support the proliferation of B16 melanoma cells. AB - It was observed that the addition of zinc and iron tartrate complexes to the Eagle's Minimal Essential Medium was sufficient to support the proliferation of murine B16 melanoma cells in this simple extracellular protein-free medium. The addition of these trace elements to the serum-depleted EMEM induced growth of B16 cells as did the addition of serum. This implicates that this test, often used in the search for mitogenic factors, does not discriminate between the real mitogens and the nutrients necessary for cell growth. PMID- 8500629 TI - Nuclear bodies in Paneth cells of the rat. AB - Three types of nuclear bodies were identified in the Paneth cells of rat small intestine: simple nuclear bodies (type I), small complex nuclear bodies (type III) and large complex nuclear bodies (type IV). The entire simple nuclear bodies and the capsules of complex nuclear bodies were composed of 5 nm filaments. The core of small complex nuclear bodies resembled the interchromatin, while the core of large complex nuclear bodies resembled the granular and fibrillar components of the nucleolus. The Paneth cells of the rat small intestine were found to be especially rich in nuclear bodies: about 80% of nuclear profiles contained one or more sections through nuclear bodies. We suggest that a large number of nuclear bodies in Paneth cells is related to a high rate of protein synthesis in these cells. PMID- 8500630 TI - Comparison of nuclear protein SH/DNA ratio in species differing in 2C DNA content and dynamics of DNA endoreplication. AB - Double fluorescence staining with o-phthalaldehyde (OPT) and propidium diiodide (PI) was applied to measure the nuclear protein SH/DNA ratio in species differing in 2C DNA content. It has been shown that protein SH/DNA ratio decreases along with the increase in 2C DNA content. In endosperm, this ratio is higher than in meristematic nuclei of the same species. PMID- 8500631 TI - Chloramphenicol, an inhibitor of mitochondrial protein synthesis, inhibits myoblast fusion and myotube differentiation. AB - Chloramphenicol (100 micrograms/ml), an inhibitor of mitochondrial protein synthesis, inhibits the fusion of myoblasts isolated from chick embryo pectoral muscle in both, serum supplemented and serum-free culture conditions. This inhibition of myotube formation appeared reversible only in the defined media. Tryptose phosphate broth and nucleosides, when added in the presence of chloramphenicol, were able to restore the cell capacity to proliferate but not to fuse and differentiate. PMID- 8500632 TI - New zodiacal influences on Chinese family formation: Taiwan, 1976. AB - Although Chinese folklore holds that the Dragon Year is an auspicious time to have a birth, notable increases in Chinese fertility in Dragon Years did not occur before 1976. Demographic explanations for the belated occurrence of this phenomenon rely on the notion of natural fertility: that is, couples' lack of modern contraception had kept such decisions outside the realm of choice. The decomposition performed in this article, however, shows that the bulk of the 1976 Dragon Year baby boom on Taiwan was due to strategies that had always been available: marriage timing, abortion, and coital behavior. The natural fertility paradigm thus is insufficient in explaining the motivation for this behavior and should be complemented by institutional approaches. PMID- 8500633 TI - Fertility in Botswana: the recent decline and future prospects. AB - Recent estimates of fertility in Botswana suggest a rapid decline of more than two births per woman between 1981 and 1988. This paper proposes that the baseline fertility was overestimated but that nonetheless fertility declined by about one birth per woman during the 1980s. The decline in fertility was linked to a deterioration in social and economic conditions caused by a major drought in the early 1980s and to the increased availability of family planning services in the same period. Fertility apparently began to rebound in the late 1980s in response to improved conditions, which came about as a result of a successful drought relief program. Future declines in fertility depend on the continued success of the family planning program, particularly in rural areas. PMID- 8500634 TI - A new look at the determinants of nonnumeric response to desired family size: the case of Costa Rica. PMID- 8500635 TI - Writing the names: marriage style, living arrangements, and first birth interval in a Nepali society. AB - Using data from a Nepali population, this analysis argues that marriage style and postmarital living arrangements affect coital frequency to produce variations in the timing of first birth after marriage. Event history analysis of the first birth interval for 149 women suggests that women's autonomy in marriage decisions and marriage to cross-cousins accelerate the pace of entry into first birth. Extended-household residence with reduced natal kin contact, on the other hand, significantly lengthens the first birth interval. These findings are consistent with previous arguments in the literature while offering new evidence for the impact of extended-family residence on fertility. PMID- 8500636 TI - Marriage selection and mortality patterns: inferences and fallacies. AB - Researchers have long wondered whether marital-status differences in mortality arise largely from selection mechanisms or from causal processes typically known as marriage protection. Unfortunately, many investigators have relied on aggregate patterns of mortality differentials--such as age schedules of excess mortality in the single population or the relationship between the level of excess mortality and the relative size of the single population--to make inferences about the relative importance of selection and causal processes. In this paper, a simple mathematical simulation model is used to demonstrate that many inferences derived from observed patterns are simply not justified. This finding highlights the importance of prospective data for assessing the relative importance of selection and causal factors in accounting for the excess mortality of the unmarried. PMID- 8500637 TI - Gender differences in economic well-being among the elderly of Java. AB - With populations aging rapidly in many developing nations, issues of economic dependency among the elderly are of increasing importance. Using data from a 1986 survey of the elderly on Java, Indonesia, I describe gender differences in economic well-being and identify characteristics associated with economic disadvantage. At both the individual and the household level, older women have fewer resources than older men. Even within categories of support (work income and remittances), women have lower levels of well-being. Gender differences in household-level economic well-being are due primarily to differences in household structure and in levels of skills. Gender differences in individual receipts (from all sources) are more complicated, but can be understood more clearly with reference to gender differences in skills levels (literacy, language, job skills), current work status and authority, and domestic authority. PMID- 8500638 TI - Income growth among nonresident fathers: evidence from Wisconsin. AB - This study examines the changes over time in the personal incomes of nonresident fathers--whether divorced or nonmarital--in Wisconsin. Using data from the Wisconsin Court Record data base and the Wisconsin Department of Revenue, the authors examine the incomes of these fathers over the first seven years following a divorce or the initiation of a paternity suit. They also study separately the income patterns of initially poor nonresident fathers and fathers whose nonresident children receive welfare. The most important finding is that the incomes of nonmarital fathers, which typically are low in the beginning, increase dramatically over the years after paternity establishment--often to a level comparable with the incomes of divorced fathers. On the basis of their findings, the authors conclude that failing to establish child support obligations for nonresident fathers simply because their incomes are initially low does not appear justified. PMID- 8500639 TI - Locational returns to human capital: minority access to suburban community resources. AB - The suburbanization of racial and ethnic minorities is analyzed in terms of the locational resources provided by their communities of residence. In suburbs in the New York CMSA, non-Hispanic whites and Asians, on average, live in communities with higher average socioeconomic status, while Hispanics and blacks live in the less desirable suburbs. Models predicting suburban socioeconomic status for each racial/ethnic group show that whites and Hispanics receive consistent returns on income, acculturation, and family status. Asians' locational patterns differ because they are unrelated to measures of acculturation; for blacks, locational outcomes correspond least to any of these human capital characteristics. PMID- 8500640 TI - Black suburbanization in the 1980s. PMID- 8500641 TI - The socioeconomic costs of teenage childbearing: evidence and interpretation. AB - There is little evidence to support the reasons suggested by Hoffman et al. for treating the results based on the NLSYW as outliers. There is even some evidence that might lead one to favor the NLSYW estimates. After some investigation, which of the range of within-family estimates across data sets is most accurate remains unsettled (although exploring differences in cross-sectional estimates from the sisters subsamples seems promising). In addition, we believe there is evidence to support the hypothesis that within-family estimates are upwardly biased because of within-family heterogeneity and endogeneity, but the importance and magnitude of such bias is also an open question. Although we have highlighted here what we believe to be the main points of disagreement between ourselves and Hoffman et al., we hope readers will not lose sight of the areas of agreement between the two studies, which are substantial, or of the empirical support for our key findings that Hoffman et al.'s replication study has provided. To us, the findings of both studies suggest that future research should account empirically for potential biases from (possibly unmeasured) heterogeneity in family background. Because the prevailing beliefs about the consequences of teen childbearing have been based on cross-sectional comparisons that lack detailed family background controls, these beliefs now should be open for reconsideration and should be subjected to reevaluation. Several recent empirical attempts have been made to take heterogeneity or endogeneity bias into account. These studies support this conclusion and caution against drawing causal inferences from existing estimates of the effects of teen births. We continue to recognize the limitations of currently available methods and data for accounting for unobserved heterogeneity and selectivity (e.g., Griliches 1979; Manski 1989). Therefore we encourage the enhancement of data sets and the continued empirical investigation of questions that have been raised about possible biases of sibling estimation and other methodological approaches. We hope that with new rounds of research, advances will continue to further the understanding of these important social processes. Given the difficulty of accounting adequately for selection into teen childbearing across and within populations, and even within families, and given the conflicting within-family estimates, we believe that the size of any "true effects" of teen births on socioeconomic status must be considered an open question. PMID- 8500642 TI - Cell surface C-reactive protein of rainbow trout lymphocytes. AB - C-reactive protein (CRP) expressed on rainbow trout (Oncorhynchus mykiss) lymphocytes was investigated to determine what role CRP might have on lymphocyte function. C-reactive protein was detected on the surface (S-CRP) of 25% of peripheral blood lymphocytes (PBL) and 4% of head kidney lymphocytes (HKL) by flow cytometry of cells labelled with biotinylated rabbit anti-rainbow trout CRP IgG and fluorescent-coupled avidin. Purified CRP, when added to cells in culture, bound to both PBL and HKL. Stimulation of PBL and HKL by concanavalin A, phytohemagglutinin, or lipopolysaccharide increased the percentage of S-CRP positive cells, which suggests the production of CRP by lymphocytes. Treatment of lymphocytes with anti-rainbow trout CRP IgG and complement decreased the number of S-CRP-positive cells. PMID- 8500643 TI - Glucocorticoid effects on natural and humoral immunity in mallards. AB - Two studies were conducted to determine the effects of dexamethasone (DEX) on immune function in mallard ducks. Each day ducks were injected intramuscularly with DEX at doses ranging from 0.2-4.0 mg/kg for 28-30 days. Physiologic effects consistent with high dose glucocorticoid (GC) treatment were observed at the 4 mg/kg dose, and included significant body weight loss, lowered hematocrit, and elevated alanine aminotransferase (ALT) activity. At all doses, effects of DEX on the immune system were observed. When DEX was given at 0.2 mg/kg/day, significant suppression of primary IgG antibody titers to sheep erythrocytes (SRBC) was observed. At 1 mg/kg/day, primary IgM and secondary IgM and IgG titers were suppressed as well. These doses of DEX also produced significant elevation in natural killer cell (NKC) activity of peripheral blood mononuclear cells (PBMNC). Removal of adherent cells from the PBMNC prior to NKC assay eliminated the enhancement in NKC activity. Based on these results, it was postulated that the elevation in NKC activity may be due to suppression by DEX of monocyte production of prostaglandin-E2 (PGE-2) resulting in the release of NKC activity from the inhibitory effects of PGE-2. This hypothesis was supported by a measured decrease in PGE-2 production during the NKC assay by cells from DEX-treated birds. Furthermore, an enhanced NKC activity could be reproduced in vitro with the addition of indomethacin or DEX to NKC cultures containing adherent cells from PBMNC. Direct effects of DEX on nonadherent cell NKC activity and lymphocyte viability were only observed at high concentrations (10(-4) M) of DEX, while the phagocytic activity of adhered blood monocytes was inhibited at 10(-6) M DEX. The suppressed phagocytic activity may contribute to the suppressed antibody responses observed in DEX-treated birds. Together, these results support an indirect immunomodulatory effect of DEX on NKC activity and perhaps antibody responses in vivo via altered monocyte function in mallard ducks. PMID- 8500644 TI - J-chain-positive cells in immunodeficient chickens. AB - Before and after hatching, J-chain-positive cells (JPC) were observed by immunoelectron microscopy in lymphoid tissues from chickens that had been chemically bursectomized (Bx) in ovo. These JPC were detected in spleens both of normal and Bx birds. Subcellular localization of J chains showed more variations in normal than Bx chickens. From these findings, JPC could be divided into JPC subpopulations in chickens. PMID- 8500645 TI - In vitro phenoloxidase activity in the blood of Ciona intestinalis and other ascidians. AB - The presence and activation of phenoloxidase in the blood of Ciona intestinalis and other ascidians was investigated in vitro. In C. intestinalis, phenoloxidase was found to exist in the cells as a proenzyme and to be activated by proteases. The microbial carbohydrates, LPS or laminarin, also enhanced enzyme activity but a similar effect was not achieved with other sugars. Calcium was not essential for enzyme activity and no enzyme suppression was seen at high calcium concentrations. Prophenoloxidase activation by LPS was further found to be dose related and inhibited by PTU and tropolone. Since benzamidine and STI reduced phenoloxidase activity in cell lysate supernatants, activation may involve other factors, possibly a serine protease. Lastly, as phenoloxidase activity was detected in the blood cells (usually the morula cells) of eight other ascidian species, it appears that it is widely distributed in the blood of this group of invertebrates. PMID- 8500646 TI - Localized expression of the H-ras proto-oncogene during Ilyanassa development. AB - We have immunostained Ilyanassa embryos with an antibody to the ras protein and shown that the ras gene (1) is not expressed from early cleavage through the gastrula stage, but (2) is expressed during organogenesis by both normal and lobeless embryos, (3) that the ras protein is first synthesized from the third day of development in the normal embryo and from the fifth day of development in the lobeless embryo, and (4) that the expression of the ras protein is localized in mesodermal lineages of both normal and lobeless embryos. PMID- 8500647 TI - A model for pattern formation of hypostome, tentacles, and foot in hydra: how to form structures close to each other, how to form them at a distance. AB - A model for head, tentacle, and foot formation in Hydra is proposed. The model shows that systems which suggest a positional information scheme may be realized by a set of hierarchically coupled pattern forming systems: a structure generates the precondition for a second structure but excludes this structure locally. In this way, a well-regulated neighborhood of structures is enforced. According to the model, head, tentacle, and foot formation are under the control of separate activator-inhibitor systems. These systems are coupled via the source density. The head activator increases the source density and the activation takes place preferentially in regions of highest source density. The foot activation has the opposite behavior. It appears at the lowest source density and lowers the effective source density further. Therefore, head and foot activation appear preferentially at opposite positions of the field. Tentacle activation occurs in the region of highest source density that is not occupied by a primary head activation. Tentacle activation requires a certain threshold level of the source density. As shown by computer simulations, the model accounts for many so far unexplained observations, such as during regeneration the tissue obtains tentacle like properties until the newly formed hypostome displaces the tentacles into a subhypostomal region. Since no direct inhibition between head and foot is involved, both structures can appear close to each other in experimental situations. The dramatic effects of treatment with diacylglycerol, such as the formation of new tentacles preceding the formation of additional hypostomes, become understandable under the simple assumption that the agent increases the source density. Budding is regarded as a trigger of a second head activator maximum. Budding can occur only beyond a minimum distance from the head due to the head inhibitor and beyond a minimum distance from the foot since the source density would be too low there. The model accounts for the periodic spacing of secondary structures around a primary organizing region such as that found in the arrangement of leaves and flower elements in plants around the primary meristem. Similarities to the vulva development of Caenorhabditis elegans and to the segmentation of insects are discussed. PMID- 8500648 TI - Development of myelin mosaicism in the optic nerve of heterozygotes of the X linked myelin-deficient (md) rat mutant. AB - The oligodendrocyte population of the optic nerve has been suggested to arise either from a radial migration of neuroepithelial cells of the optic stalk or from the longitudinal migration of progenitor cells into the optic nerve from the brain, via the optic chiasm. Female heterozygotes of the X-linked myelin deficient (md) rat trait show a marked mosaic pattern of myelination of the optic nerves. This degree of mosaicism is not observed in other parts of the central nervous system. A total of 235 optic nerves from female rats of from 3 weeks to 24 months of age were examined by light microscopy. Nerves (104), from rats of all ages, showed defects in myelination consisting of distinct patches of non myelination, often sharply demarcated from adjacent areas of normally myelinated axons. In some animals the abnormality was grossly apparent as areas of transparency within the intact optic nerves. In the majority of optic nerves showing mosaicism, defects in myelination were observed along the whole length of the nerve. However, a worsening of the defect toward the retinal end of the nerve was noted in 15 optic nerves, and an additional 11 nerves showed a defect in this region alone. It was also found that a number of rats had mosaicism in only one optic nerve. The preferential involvement of the retinal end of the optic nerves, and the asymmetrical involvement of the optic nerves within individual rats, is interpreted as indirect evidence in support of the proposed longitudinal migration of the oligodendrocyte precursor into the optic nerve. PMID- 8500650 TI - Dynamics of germ plasm localization and its inhibition by ultraviolet irradiation in early cleavage Xenopus embryos. AB - In the spawned Xenopus egg, germ plasm is found as cytoplasmic islands spread over a wide cortical region of the vegetal pole. However, by the blastula stage, the same material is found concentrated into a few large blastomeres at the floor of the blastocoel. Components of the germ plasm can be specifically labeled with a fluorescent dye, DiOC6(3), permitting the dynamic movements of germ plasm localization to be followed in live embryos via time-lapse confocal scanning optical microscopy. During the first cell cycle, the small islands initially appear to be fixed to the vegetal yolk mass and to move with it during the cortical rotation. After rotation, the islands appear to be released from the vegetal yolk mass and to begin fusing with one another. During early cleavages, the germ plasm aggregates into large islands at the vegetal pole in a movement dependent on microtubules. Two distinct actions can be discerned: (1) a continuous process of local fusing and (2) periodic surface contraction waves (SCWs) that gather the islands toward the vegetal pole. These SCWs are inhibited by ultraviolet irradiation of the vegetal pole. Near the vegetal pole, germ plasm patches ingress into the embryo's interior along the cleavage furrow in periodic movements contemporaneous with the SCWs. PMID- 8500649 TI - Two types of neonatal-to-adult fast myosin heavy chain transitions in rat hindlimb muscle fibers. AB - Adult fast myosin heavy chain (MHC) isoforms are accumulated in fibers of rat hindlimb skeletal muscle which initially contain neonatal MHC at birth. The specific factors controlling these transitions are not known, but in rat and mouse muscle tissue the transition between the neonatal and adult fast MHC proteins does not appear to require continuous innervation. We have reinvestigated the role of innervation in the neonatal-to-adult fast MHC protein and mRNA transitions that occur in developing rat fast-twitch muscles using immunohistochemistry and S1 nuclease mapping. We find that neonatal MHC containing developing fibers exhibit different responses after denervation at birth regarding the disappearance of neonatal MHC and the accumulation of adult fast MHC isoforms. Immunohistochemistry shows that one fiber population loses neonatal MHC and accumulates adult fast IIB (or possibly IIX) MHC over a period of 2-3 weeks, whereas in the other population neonatal MHC does not decrease nor does the adult fast IIA isoform accumulate to high levels. The results of S1 analysis of mRNAs show that the levels of neonatal MHC mRNA do not decrease in muscles denervated at birth. We also demonstrate that in young adult rats this mRNA is reexpressed in denervated or paralyzed muscles. Since the appearance of IIB mRNA has been previously shown to be nerve-independent (S.D. Russell, N. Cambon, B. Nadal-Ginard, and R.G. Whalen, 1988, J. Biol. Chem. 263, 6370-6374), these results suggest that fibers containing neonatal MHC in rat hindlimb muscles at birth are already differentiated (i.e., preprogrammed) to accumulate either the adult fast IIA or IIB MHC isoforms and that the neonatal-to-adult MHC transitions occurring in these two fiber populations are controlled by different mechanisms. PMID- 8500651 TI - Extracellular matrix (mesoglea) of Hydra vulgaris III. Formation and function during morphogenesis of hydra cell aggregates. AB - Hydra, as a member of the phylum Cnidaria, is characterized by a body lining organized as an epithelial bilayer with an intervening extracellular matrix (ECM) termed the mesoglea. Previous studies have established that the mesoglea has components indicative of mammalian ECM such as type IV collagen, laminin, fibronectin, and heparan sulfate proteoglycan, and these components appear to play a critical role in hydra head regeneration. A remarkable feature of hydra is its ability to reorganize into its adult structure within 96 hr to 7 days from pellets formed from dissociated hydra cells. This regenerative model has been termed the hydra cell aggregate system. The present study has been designed to characterize the biogenesis of mesoglea in hydra cell aggregates and to determine its role in morphogenesis of aggregates. We find that hydra cell aggregates first form an epithelial bilayer by 12 hr of development and then subsequently develop a mesoglea. Morphogenesis of hydra structure then follows formation of the mesoglea. Immunofluorescence studies indicate that mesoglea components are first deposited between the epithelial bilayer by about 12-17 hr of pellet formation, and pulse-labeling studies indicate that the translation rate of matrix components peaks by 48-72 hr of development. Ultrastructural studies indicate that a mature mesoglea is formed by 48-96 hr of pellet formation. Drugs such as beta-aminoproprionitrile and 2,2'-dipydridyl, which interfere with the cross linking of collagens, and p-nitrophenyl-beta-D-xylopyranoside, which interferes with the addition of GAG moieties to proteoglycan core molecules, were found to reversibly block development of hydra cell aggregates. Transmission electron microscopy studies indicate that these drugs affect the ultrastructure of the mesoglea. In addition, both polyclonal and monoclonal antibodies raised to isolated mesoglea were found to block development of hydra cell aggregates. These studies indicate that (1) mesoglea formation is rapid and precedes morphogenetic processes during aggregate development, and (2) formation of mesoglea is essential for normal morphogenesis of hydra cell aggregates. PMID- 8500652 TI - Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans. AB - In Caenorhabditis elegans hermaphrodites, morphogenesis of the vulva culminates in a process called vulval eversion, whereby a passageway is made from the uterus through the vulva to the outside of the animal. We have screened for mutations causing abnormal eversion of the vulva (evl mutations) to identify new genes involved in vulval development, and found that evl mutants are relatively common after EMS mutagenesis. We also hoped to identify genes involved in lin-12 mediated cell fate decisions, since lin-12 null mutants have abnormally everted vulvae, but none of the 68 evl mutations recovered in our screen appeared to be good candidates for genes that function with lin-12. Initial genetic and phenotypic analysis of 30 evl mutations revealed that all affect the development of the uterus, but only some affect the vulval precursor cell lineages. We used laser ablation to show that the uterus and anchor cell are important for correct vulval eversion in wild type; the anchor cell is important early in the L3 stage, before the vulval cells have been generated, but not later, when vulval eversion occurs. We conclude that certain evl mutations may influence vulval eversion by primarily affecting the development of the somatic gonad, while others may affect processes required in the development of both structures. PMID- 8500653 TI - Laminin variants and integrin laminin receptors in developing and adult human smooth muscle. AB - Distribution of laminin variant chains and of laminin-binding beta 1-associated alpha integrin subunits was studied in human arterial and visceral smooth muscle during development using the immunofluorescence method. In aortic media of 10 week-old fetuses (early fetal stage of development), B1, B2, and A chains were found, and at 27 weeks of gestation (late fetal step), in addition, the S chain was revealed. In the major part of adult aortic media, staining for the B1 chain was substituted by staining for the S chain. A reasonable explanation for this is that the basement membrane of arterial SMCs contains the A-B1-B2 laminin trimer at the early fetal stage of development, a mixture of A-B1-B2 and A-S-B2 variants during the late fetal period, and the A-S-B2 form in adult media. In the intimal thickening of adult arteries, staining for A and S chains was decreased, and the B1 chain was detected, thus suggesting coexistence of A-B1-B2 and A-S-B2 variants similar to the fetal aorta. These data led us to propose that maturation of arterial SMCs is accompanied by a switch from expression of A-B1-B2 to A-S-B2 laminin, the only protein variant associated with the differentiated SMC phenotype. The M chain was not detected in fetal and adult arterial smooth muscle. In differentiated visceral SMCs from adult colon, in contrast to arterial medial SMCs, B1, S, B2, and A chains, i.e., both B1 chain- and S chain-containing laminin molecules, were present. Similar to vascular smooth muscle, the expression of A and S laminin chains in SMCs of the intestine was developmentally regulated. Of the four beta 1-associated alpha integrin subunits that have been shown to recognize laminin (alpha 1, alpha 2, alpha 3, and alpha 6), only alpha 1 was revealed during the early fetal stage of development in smooth muscle of the arteries and digestive tract. alpha 3 appeared in aortic media only during the late fetal period. In adult arterial media and smooth muscle of the colon, alpha 1 and alpha 3 were the major potential laminin-binding integrins. The spatial temporal distribution of laminin variants in developing and adult smooth muscle suggests that a variant laminin (possibly A-S-B2) interacting with its receptor (alpha 1 beta 1 or alpha 3 beta 1) may be important for maintenance of the differentiated SMC phenotype in vivo. PMID- 8500654 TI - Expression of activin mRNA during early development in Xenopus laevis. AB - Activins are members of the transforming growth factor-beta superfamily, a class of peptide growth factors that can regulate the growth and differentiation of a variety of cell types. In mesoderm induction assays, activins A and B were shown to be very potent inducers and it was only recently demonstrated that they are crucial for initial mesoderm induction in Xenopus embryos. To determine the source of activin protein for initial mesoderm induction and to investigate whether activins may play further roles in embryonic development we have examined the localization of the mRNAs encoding the activin beta A and beta B subunits in Xenopus embryos. Activin beta A and beta B mRNAs are found in the follicle cells surrounding oocytes but not in oocytes themselves or fertilized eggs. During embryogenesis activin mRNA is first detected after the midblastula transition and expression increases as development proceeds. Activin beta B mRNA is homogeneously distributed during blastula and early gastrula stages but restricted to the dorso-anterior region in neurula stage embryos. At the early tailbud stage activin expression becomes confined to the brain, eye analgen, visceral pouches, otic vesicles, and the anterior notochord. PMID- 8500655 TI - Delta function is required for bristle organ determination and morphogenesis in Drosophila. AB - Analyses of Delta (Dl) temperature-sensitive mutants reveal that reductions in Dl function during metamorphosis of Drosophila melanogaster can lead to multiplication or loss of bristle organs on the adult notum, depending on the developmental interval during which such mutants are pulsed at restrictive temperature. Site-dependent macrochaeta multiplication or loss results from pulses 0-21 hr after puparium formation (APF). Microchaeta multiplication results from pulses 7-30 hr APF, while microchaeta loss results from pulses 24-47 hr APF. Supernumerary bristle organs that develop in Dl mutants consist of the normal complement of trichogen, tormogen, neuron, and thecogen cells, and appear to arise due to the specification of super-numerary bristle first-order precursor (pI) cells within proneural groups in the developing notum. Loss of complete bristle organs in Dl mutants is correlated with the differentiation of all four progeny of the pI cell into neurons. We conclude that Dl function is required for cellular interactions central to the correct specification of pI cells within proneural groups, as well as for morphogenesis of the bristle organ itself. PMID- 8500656 TI - Sperm chemotaxis during the process of fertilization in the ascidians Ciona savignyi and Ciona intestinalis. AB - Ascidian sperm were activated and attracted to all of the surface of a whole egg. When the whole egg was separated into follicle cells, chorion and test cells, and the egg itself (naked egg), spermatozoa were activated and exhibited chemotaxis toward the vegetal pole of the naked egg. Such activation and chemotaxis were not observed around isolated follicle cells or chorion with follicle cells and test cells, suggesting that a substance released from the vegetal pole of the egg which activates the sperm and orients them to it in the perivitelline space. The chemotaxis index, which was calculated by a newly proposed method, showed that sperm-attracting activity vanished when the egg deformed, suggesting that the release of attractant through the plasma membrane is terminated at the time of fertilization. The supernatant of the egg suspension (egg seawater) showed strong sperm-activating and sperm-attracting activities, which were dialyzable, heat stable, and resistant to proteinases. Thus, these activities may be initiated by a nonproteinaceous small molecule. Spermatozoa which were previously activated with theophylline without the egg factor showed chemotactic behavior to the tip of the capillary in which egg seawater was enveloped. However, spermatozoa exhibited only activation around the tip of the capillary with theophylline. This indicates that sperm activation and chemotaxis could be controlled under a separative mechanism. PMID- 8500657 TI - Perinatal phenotype and hypothyroidism are associated with elevated levels of 21.5- to 22-kDa basic fibroblast growth factor in cardiac ventricles. AB - Control of cardiomyocyte growth and differentiation may be exercised, in part, at the level of expression of endogenous growth factors such as bFGF (basic fibroblast growth factor), believed to act locally, in an autocrine or paracrine fashion. Examination of bFGF accumulation by extract fractionation and immunoblotting indicated a 4-fold increase of an 18-kDa bFGF in adult compared to newborn rat heart ventricles. In contrast, a 22-kDa bFGF species, found to be the predominant form in newborn ventricles, displayed a 2.5-fold decrease in extracts from adult (compared to neonatal) ventricles. Since newborn rats are physiologically hypothyroid, the effect of thyroid status on the accumulation of 22-kDa bFGF in the heart was examined. A 21.5- to 22-kDa bFGF showed a 5-fold increase in extracts from hyperthyroid rat heart ventricles, compared to those from euthyroid controls. The 21.5- to 22-kDa bFGF was essentially unaffected by thyroid status in extracts from brain. Our data point to a correlation between immature or differentiated cardiac phenotype and the predominance of 21- to 22.5 kDa or 18-kDa bFGF species, respectively. Elevated levels of 21.5- to 22-kDa bFGF detected in cardiac ventricles in either physiological or experimentally induced hypothyroidism indicates that thyroid hormone may, directly or indirectly, down regulate accumulation of the higher molecular mass forms of bFGF in the heart. PMID- 8500658 TI - The SpEGF III gene encodes a member of the fibropellins: EGF repeat-containing proteins that form the apical lamina of the sea urchin embryo. AB - We have identified a gene in the sea urchin Strongylocentrotus purpuratus that encodes a protein with multiple epidermal growth factor(EGF)-like motifs. The SpEGF III cDNA sequence predicts a 570 amino acid protein with a complex domain structure similar to that of the fibropellins--the protein products of the SpEGF I gene. A putative hydrophobic leader sequence is followed by an EGF-like motif, a domain similar to complement Cls, seven tandem EGF-like repeats, and a carboxy terminal domain similar to avidin. The 2.9-kb SpEGF III mRNA is expressed from a single copy gene. SpEGF III mRNA is present at low levels in unfertilized eggs and during early cleavage, then rapidly increases in abundance between late morula and mesenchyme blastula stages to maximal levels maintained through subsequent stages. Polyclonal antisera from SpEGF III fusion proteins reveal that the protein is a 100-kDa fibropellin which is present in unfertilized eggs but does not accumulate substantially until the mesenchyme blastula stage. The protein is localized to the apical lamina, a structurally complex component of the extracellular matrix that is made up of three major proteins, two of which are the differentially spliced products of SpEGF I. The size and localization of the SpEGF III protein, and the results of immunoprecipitation assays which reveal that it is tightly associated with the products of SpEGF I, indicate that it is the third major protein component of the apical lamina. The timing of SpEGF III protein accumulation is coincident with an increase in the structural complexity of the apical lamina, and with the developmental period when the apical lamina plays an important role in gastrulation. PMID- 8500659 TI - Identity of two rat testis cDNAs. PMID- 8500660 TI - [EEG and psychophysiologic parameters in athletes with various styles of competitive activity]. PMID- 8500661 TI - [Various biochemical and functional parameters of the state of the body during long-term operator activity under extreme conditions]. PMID- 8500662 TI - [Adaptation potential of students in various phases of the ovarian-menstrual cycle]. PMID- 8500663 TI - [Differences in monthly variations of mental efficiency in healthy women as a function of the intro-extraversion factor]. PMID- 8500664 TI - [Vision and driving. Specifics of the work of a transport vehicle operator]. PMID- 8500665 TI - [Response of the human external ear muscles to sound and the probable mechanism of accompanying subjective phenomena]. PMID- 8500666 TI - [Recording of brain kinesthetic evoked potentials as a new method for studying human sensorimotor function in health and in disease]. PMID- 8500667 TI - [Choice of a descriptive model for the elastic properties of human lungs]. PMID- 8500668 TI - [Objective evaluation of professional talents of vocalists]. PMID- 8500669 TI - [Effect of exertion on contrast sensitivity]. PMID- 8500670 TI - [Age-related features of intracardiac hemodynamic shifts in healthy children during submaximal exertion as registered by echocardiography]. PMID- 8500671 TI - [Homeostatic parameters as a criterion for predicting the mastery rank of heavy weight wrestlers]. PMID- 8500672 TI - [Training effect of high-frequency electric stimulation on the human anterior tibial muscle. I. Effect on muscle force and cross-sectional area]. PMID- 8500673 TI - [Interrelationship between hematologic and muscular parameters of the oxygen transport system and work capacity level of people in endurance training]. PMID- 8500674 TI - [Study of the metabolic characteristics of slowly- and rapidly-contracting fibers in human skeletal muscle using 31P-nuclear magnetic resonance spectroscopy]. PMID- 8500675 TI - [Do potassium ions affect the contractile force of skeletal muscles during the development of fatigue?]. PMID- 8500676 TI - [Isokinetic exercise and voluntary activation before and after fatigue of the musculus quadriceps femoris]. PMID- 8500677 TI - [Electrophysiologic correlates of initiation and termination of voluntary movement]. PMID- 8500678 TI - [Cardiac regulatory mechanisms at rest in top level athletes]. PMID- 8500679 TI - [Clinico-physiologic methods of examination in staged diagnosis and management of patients with acute heart diseases]. PMID- 8500680 TI - [Blood pressure responses to orthostasis in arterial hypertension. II. Diagnosis of early stages of the disease]. PMID- 8500681 TI - [Information load during mental activity and asthenic syndrome]. PMID- 8500682 TI - [Topography of brain electric potentials in schizophrenia with depression syndrome and thought disorders]. PMID- 8500683 TI - [Role of biorhythmologic processes in adaptation mechanisms and correction of regulatory dysfunctions]. PMID- 8500684 TI - [The problem of oxygen regimen under extreme conditions]. PMID- 8500685 TI - Let our voices be heard and amplified. The time is now! AB - The future health and well-being of all our citizens is at stake. We must make our voices heard, we must amplify their effect by mobilizing our entire society. We are doing this not for ourselves, but for the country, for all our citizens, and for our future generations. As citizens, we are obliged to help our administration and Congress set their agenda. If there was ever a time to voice the need to support biomedical research, it is now. Please give this your highest priority. If we do not take up this responsibility, we will have no one else to blame if medical progress is retarded due to inadequate funding. Rise to the occasion and meet the challenge. Let our voice be amplified and be heard, loudly and clearly. Do not wait; do not postpone even for a moment. NOW. PMID- 8500686 TI - On giraffes and peer review. PMID- 8500687 TI - The reductive pentose phosphate cycle for photosynthetic CO2 assimilation: enzyme modulation. AB - The reductive pentose phosphate cycle (Benson-Calvin cycle) is the main biochemical pathway for the conversion of atmospheric CO2 to organic compounds. Two unique systems that link light-triggered events in thylakoid membranes with enzyme regulation are located in the soluble portion of chloroplasts (stroma): the ferredoxin-thioredoxin system and ribulose 1,5-bisphosphate carboxylase/oxygenase-Activase (Rubisco-Activase). The ferredoxin-thioredoxin system (ferredoxin, ferredoxin-thioredoxin reductase, and thioredoxin) transforms native (inactive) glyceraldehyde-3-P dehydrogenase, fructose-1,6-bisphosphatase, sedoheptulose-1,7-bisphosphatase, and phosphoribulokinase to catalytically competent forms. However, the comparison of enzymes reveals the absence of common amino acid sequences for the action of reduced thioredoxin. Thiol/disulfide exchanges appear as the underlying mechanism, but chloroplast metabolites and target domains make the activation process peculiar for each enzyme. On the other hand, Rubisco-Activase facilitates the combination of CO2 with a specific epsilon amino group of ribulose 1,5-bisphosphate carboxylase/oxygenase and the subsequent stabilization of the carbamylated enzyme by Mg2+, in a reaction that depends on ATP and ribulose 1,5-bisphosphate. Most of these studies were carried out in homogeneous solutions; nevertheless, a growing body of evidence indicates that several enzymes of the cycle associate either with thylakoid membranes or with other proteins yielding supra-molecular complexes in the chloroplast. PMID- 8500688 TI - Perianesthetic thermoregulation and heat balance in humans. AB - General anesthesia markedly impairs normal control of body temperature, reducing the threshold (triggering core temperature) for thermoregulatory vasoconstriction from approximately 37 to approximately 34.5 degrees C. Sweating and active vasodilation thresholds similarly are increased, widening the range of temperatures not triggering regulatory compensations from approximately 0.2 to approximately 4 degrees C. However, once initiated, the gains (slopes of response intensity vs. core temperature curves) and maximum intensities of thermoregulatory responses are nearly normal. Intraoperative core temperature initially decreases rapidly because anesthetic-induced inhibition of tonic thermoregulatory vasoconstriction causes a core-to-peripheral redistribution of body heat. The subsequent slower, linear decrease in body temperature results from heat loss exceeding metabolic heat production. And finally, after 3-4 h of anesthesia, core temperature stabilizes at an abnormally low value. In patients experiencing minimal heat loss, and therefore not becoming sufficiently hypothermic to trigger vasoconstriction, this plateau can be passive steady state in which heat loss equals production. Conversely, patients becoming sufficiently hypothermic will trigger thermoregulatory vasoconstriction that both decreases cutaneous heat loss and sequesters some metabolic heat in the core. Epidural and spinal anesthesia also cause core hypothermia by inhibiting tonic thermoregulatory vasoconstriction, producing an internal redistribution of heat from the warm core to cooler peripheral tissues. Core hypothermia provokes thermoregulatory responses including vasoconstriction (above the block level) and shivering. Nonetheless, many patients feel warmer after induction of regional anesthesia, apparently because perceived skin temperature is elevated. The following review will focus on anesthetic-induced impairment of normal thermoregulatory control and the resulting alterations in heat balance. PMID- 8500689 TI - Growth hormone-releasing hormone and interleukin-1 in sleep regulation. AB - Growth hormone-releasing hormone (GHRH) and interleukin-1 (IL-1) are putative endogenous sleep-promoting substances. Evidence is reviewed showing that, 1) GHRH and IL-1 promote non-rapid eye movement sleep (NREMS); 2) if their production is enhanced, sleep is enhanced; and 3) if they are inhibited using either specific antibodies or peptide antagonists, sleep is reduced. Both are in the brain and both are also indirectly linked to sleep/wake cycles by various other evidence, e.g., growth hormone release and IL-1 plasma levels vary in phase with sleep/wake cycles. Finally, their actions are directly linked to each other; e.g., IL-1 induced growth hormone release is mediated via GHRH. The evidence reviewed strongly implicates both GHRH and IL-1 as key components in humoral sleep regulation. Humoral theories of sleep regulation are complementary to neural theories; both mechanisms affect each other and undoubtedly continuously interact to regulate sleep/wake cycles. PMID- 8500690 TI - Spermidine/spermine N1-acetyltransferase--the turning point in polyamine metabolism. AB - Polyamines are thought to have several vital roles in cell growth and differentiation. The highly regulated polyamine metabolic pathway provides cells with the ability to finely control the intracellular concentration of these ubiquitous polycations. Although earlier studies of regulation of polyamine content were concentrated on the biosynthetic reactions, recently the importance of the catabolic processes, particularly the highly regulated acetylation step in polyamine degradation, has become apparent. This work has led to an understanding of how a cell may, in a tightly controlled manner, facilitate the breakdown, excretion, cycling, and/or intracellular shuttling of the polyamines. This myriad of possibilities appears to be regulated initially at a single rate-limiting enzymatic step, the N1-acetylation of spermidine or spermine, by spermidine/spermine N1-acetyltransferase (SSAT). Recent cloning of the human SSAT gene has facilitated a more detailed study of this enzyme. SSAT appears to have a role in the determination of tumor sensitivity to a new class of antineoplastic agents. The further study of SSAT and the associated polyamine metabolism should provide a better understanding of the regulation and function of these cations. PMID- 8500691 TI - Lysine 2,3-aminomutase: is adenosylmethionine a poor man's adenosylcobalamin? AB - The interconversion of lysine and beta-lysine, which is catalyzed by lysine 2,3 aminomutase, is formally similar to the isomerization reactions catalyzed by adenosylcobalamin-dependent aminomutases. However, lysine 2,3-aminomutase is activated by S-adensoylmethionine and not by adenosylcobalamin. Lysine 2,3 aminomutase also contains [FeS] clusters, Co(II), and pyridoxal 5'-phosphate, all of which are required for maximum activity. Lysine 2,3-aminomutase acts through a mechanism akin to that of the adenosylcobalamin-dependent enzymes in which substrate radicals are intermediates. However, the 5'-deoxyadenosyl moiety of S adenosylmethionine mediates hydrogen transfer in place of the 5'-deoxyadenosyl moiety of adenosylcobalamin. 5'-Deoxyadenosine is an intermediate in adenosylcobalamin-dependent reactions and in the reaction of lysine 2,3 aminomutase. The 5'-deoxyadenosyl radical, derived either from adenosylcobalamin or S-adenosylmethionine, appears to participate in these reactions. Similarly, the ribonucleotide reductase from Lactobacillus leichmanii is activated by adenosylcobalamin, whereas the ribonucleotide reductase from anaerobically grown Escherichia coli is activated by S-adenosylmethionine and an activating enzyme. The 5'-deoxyadenosyl radical seems to participate in the activation of both reductases. Therefore, both adenosylcobalamin and S-adenosylmethionine appear to serve as sources of 5'-deoxyadenosyl radicals in nature. S-Adenosylmethionine is not as chemically elegant a molecule as adenosylcobalamin, so it may be regarded as "a poor man's adenosylcobalamin." PMID- 8500692 TI - Stereochemistry of a multistep/bipartite methyl transfer reaction: thymidylate synthase. AB - Atomic structures of thymidylate synthase (TS) reveal key steps in a multi-step reaction and show quantitatively how conformation change is involved in mediating the methyl transfer reaction catalyzed by TS. Numerous alterations in TS produced by mutation, screened by complementation, and further characterized can be understood in terms of the structure and profound structure change required during the TS reaction. PMID- 8500693 TI - Sensory circumventricular organs and brain homeostatic pathways. AB - Circumventricular organs (CVOs), small structures bordering the ventricular spaces in the midline of the brain, have common morphological and endocrine-like characteristics that distinguish them from the rest of the nervous system. Among their unique features are cellular contacts with two fluid phases--blood and cerebrospinal fluid--and neural connections with strategic nuclei establishing circuitry for communications throughout the neuraxis. A variety of additional morphological and functional characteristics of the CVOs implicates this group of structures in a wide array of homeostatic processes. For three of the circumventricular organs--the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT), and the area postrema (AP)--recent findings demonstrate these structures as targets for blood-borne information reaching the brain. We propose that these three sensory CVOs interact with other nuclei in the maintenance of several homeostatic processes by way of neural and humoral links. We emphasize the collective role of brain CVOs in the maintenance of body fluid homeostasis as a model for the functional integration of these fascinating "windows of the brain" within central neurohumoral systems. PMID- 8500694 TI - Structure-function properties of human platelet 12-lipoxygenase: chimeric enzyme and in vitro mutagenesis studies. AB - Mutant and chimeric lipoxygenases were expressed in human embryonal kidney 293 cells to assess the importance of amino acids and domains for catalytic activity and positional specificity of molecular oxygen insertion. Histidines 360, 365, and 540, when changed to glutamine residues, completely abolished human platelet 12-lipoxygenase activity. Altered histidines at positions 355, 383, and 392 retained enzymatic activity. The former three histidines could possibly serve as ligands for the catalytically essential non-heme iron atom. Amino acids adjacent (residues 398-417) to the five centrally located histidines conserved among all plant and animal lipoxygenases controlled to a limited extent the positional specificity of oxygenation of 12-lipoxygenase. Variant A417I and the triple variant K416Q/A417I/V418M, designed to introduce 15-lipoxygenase substitutions, transformed the platelet 12-lipoxygenase that synthesizes exclusively 12 hydro(pero)xy-eicosatetraenoic acid (12-H(P)ETE) to an enzyme capable of 10-20% 15-lipoxygenation. When all amino acids between positions 398-429 of 12 lipoxygenase had the corresponding 15-lipoxygenase sequence, the enzyme made 66% 15-lipoxygenase products. The latter enzyme had markedly reduced enzyme activity, though, indicating an apparent shift in the optimal alignment of substrate at the active site for hydrogen atom abstraction. The platelet enzyme could not be altered to form 5-lipoxygenase products by similar manipulations of sequence within this region. Chimeric enzymes consisting of an NH2-terminal segment from one lipoxygenase and the COOH terminus from another lipoxygenase or large substitutions resulted in nonfunctional enzymes. NH2-terminal extensions, but not short deletions, could be tolerated functionally. These studies provide some new insights into lipoxygenase structure-function in the absence of an unresolved three-dimensional structure. PMID- 8500695 TI - 65-kDa protein binds to destabilizing sequences in the IFN-beta mRNA coding and 3' UTR. AB - The transient expression of human interferon (IFN-beta) gene in response to viral induction is regulated both at the transcriptional and posttranscriptional levels. The decrease in levels of IFN-beta mRNA, which requires protein synthesis, is due to transcriptional repression as well as a rapid turnover of beta mRNA. Previous studies have shown the presence of two destabilizing sequences, one in the 3' untranslated region (UTR) and the other in the coding region. We have shown in this study that the coding region destabilizing element resides in the 3' end of the coding region (+538 to +637) and that the degradation does not require the translation of IFN-beta mRNA through its coding region. In addition, we have identified three domains of 19, 20, and 29 nucleotides long that specifically bind a 65-kilodalton (kDa) cytoplasmic protein. One of the binding sites is in the 3' end of the coding region and the other two in the 3' UTR. All these regions are AU-rich and show considerable homology to each other. Interestingly, the levels of the 65-kDa protein was increased after poly rI.rC induction. We suggest that this 65-kDa protein is a component of the IFN-beta mRNA destabilizing complex or plays a role in the degradation of IFN-beta mRNA. PMID- 8500696 TI - Chronic gastritis: prevalence in the French population. CIRIG. AB - Chronic gastritis (CG) which can be associated with severe complications, is a frequent phenomenon in gastroenterological practice. No data concerning the prevalence of GC are available in France. The aim of this study was to evaluate the prevalence of CG on biopsy specimens in the French population. All outpatients coming from different towns of seven French areas and undergoing an upper endoscopy on one or two randomly selected consecutive days were included in the study. A case report form was filled out and 5 biopsy specimens were taken from the fundus and antrum. Pathologists graded the specimens on the basis of Whitehead's classification. Seven hundred and forty-two patients were enrolled by 102 private gastroenterologists. Mean age was 53 years; 52% were males. Endoscopically, the gastric mucosa was abnormal in 53%. Superficial and atrophic CG was diagnosed in 53% of cases. Superficial gastritis was observed in 101 patients (14%), antral chronic atrophic gastritis (CAG) in 189 (26%) and fundic CAG in 17 (2%). Patients with CAG were significantly older than the other patients. There were more smokers and heavy alcohol drinkers in the group of CAG patients. Endoscopy and histology were in accordance in only 55.2% of the patients: most cases of CAG were not detected by endoscopy. These results are similar to other studies in European populations. The principal pattern among the various types of gastritis was CAG. The other forms were rare. Autoimmune gastritis was uncommon in this French population (4% of the CAG patients). PMID- 8500697 TI - [Electrogastrography: responses to food and sham feeding and relationships with gastric emptying of solids in men]. AB - Cutaneous electrogastrography is a non invasive method to study gastric electromechanical activity. The aim of this work was to determine the amplitude of electrogastrographic (EGG) activity a) during fasting, b) after a meal, c) following vagal stimulation by sham feeding, and to determine the relationship between gastric emptying of solids and EGG activity. EGG activity was recorded in eight healthy subjects in various experimental conditions, twice after sham feeding, twice after a meal, and once during the simultaneous scintigraphic assessment of gastric emptying of the solid component of a meal. During one of the sham feeding tests, subjects were intubated and acid secretion was measured. The EGG signal amplitude was continuously monitored and an intercorrelation function (IF) was calculated using the Fast Fourier Transforms of electrical activity recorded by 2 cutaneous electrodes placed on the epigastric area. During fasting, IF was usually of low amplitude with occasional short increases of amplitude. Sham feeding without intubation rarely induced an early and brief increase in IF amplitude (2 of 8 subjects). Sham feeding-induced acid secretion was negatively correlated with IF amplitude (r = 0.78, P = 0.02) suggesting a motor inhibition associated with vagally stimulated acid secretion. When given orally, meals induced an increase in IF amplitude, but there was major intra- and interindividual variations. There was no significant correlation between the IF increase and the half emptying time for solids (r = 0.62, P = 0.10). This study shows that the high variability of EGG activity during fasting considerably hampers the analysis of changes induced by any stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500698 TI - [Multivariate analysis of clinical signs, parameters of anorectal manometry, defecography, transit time of radiopaque markers in 76 patients complaining of fecal incontinence]. AB - The aim of this study was to evaluate clinical symptoms, disease past-history, and parameters of anorectal manometry, defecography, and radiopaque pellet transit time in anal incontinence by multivariate analysis. We studied 76 patients, 68 women and 8 men, who complained of anal incontinence, excluding that due to obstetrical lesions. All patients were asked to complete a standard questionnaire. Results indicated that: a) hemorrhoidectomy, hysterectomy, and cholecystectomy appeared to play a role, b) daily incontinence for air or liquid stools is more frequent after hemorrhoidectomy, c) decreased resting pressure of the upper part of the anal canal was observed mainly after hysterectomy, d) decreased resting pressure of the upper part of the anal canal could be a factor of poor prognosis after treatment, e) anal incontinence in men was secondary to traumatic lesions of the anal sphincter in 7 of 8 cases. PMID- 8500699 TI - [Systemic manifestations associated with chronic inflammatory bowel diseases]. PMID- 8500700 TI - [Digestive hemorrhage caused by congestive gastropathy in a patient with liver cirrhosis: emergency treatment by transjugular intrahepatic portosystemic anastomosis]. AB - A 34-year-old woman with liver cirrhosis and portal hypertension was admitted for gastric bleeding due to congestive gastropathy. Her past medical history included 4 episodes of variceal rupture within the last 5 months. As medical treatment was a failure, an emergency transjugular intrahepatic portosystemic shunt was successfully performed, resulting in a marked drop in portal pressure (from 32 to 15 mm Hg) and a subsequent arrest of acute hemorrhage. Four months later, no recurrent bleeding has been observed and the shunt has remained patent as documented by duplex Doppler sonography. PMID- 8500701 TI - [Portal cavernoma compressing the bile duct. Apropos of three cases]. AB - Three cases of biliary tract compression caused by a cavernous transformation of the portal vein are reported. Revealing symptoms of biliary disease were anicteric and asymptomatic cholestasis in one patient, and cholangitis and obstructive jaundice in one case each. Endoscopic retrograde cholangiograms showed that the compression was located in the common bile duct in two cases and in the main bile duct in one. The responsibility of the portal cavernoma was established by the disappearance of jaundice after splenorenal shunt in one case. Biliary consequences of a portal cavernoma are very uncommon. Compression by the turgescent venous network combined with a sclero-inflammatory reaction of the biliary tract are the most likely causes. PMID- 8500702 TI - [Angiosarcoma of the aorta revealed by an intestinal metastasis]. AB - We report a case of aortic endothelioma revealed by intestinal metastasis in a man who was admitted for severe anemia, left heart failure, and fatal ileo mesenteric infarction. This is the 13th published case of aortic endothelioma, and the first case revealed by intestinal metastasis. It illustrates the value of the magnetic resonance imaging for the detection of an aortic tumor when intestinal angiosarcoma has been diagnosed. The surgical treatment could improve an otherwise very poor prognosis. PMID- 8500703 TI - [Membranous glomerulonephritis associated with primary biliary cirrhosis: a pathogenic role of anti-M2 antibodies?]. PMID- 8500704 TI - [Prevalence of hepatitis C virus antibodies in a hospital population]. PMID- 8500705 TI - [Acute cytolytic hepatitis and morbilliform eruption caused by ingestion of griseofulvin]. PMID- 8500706 TI - [Cholestasis induced by roxithromycin in a patient with a past history of pregnancy intrahepatic cholestasis]. PMID- 8500707 TI - [Ultrasound endoscopic study of esophageal wall in systemic scleroderma]. PMID- 8500708 TI - [Ultrasound endoscopic aspect of lymphocytic gastritis]. PMID- 8500709 TI - [Diabetes mellitus revealing chronic pancreatitis of probably tuberculous origin]. PMID- 8500710 TI - [Arteriovenous malformations and hormonal contraceptives]. PMID- 8500711 TI - [Liver abscess revealing Crohn's disease]. PMID- 8500712 TI - [Determination of serum bile acids in hepatic pathology]. PMID- 8500713 TI - Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests. AB - Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests. PMID- 8500714 TI - [The patient complaining about fecal incontinence does not complain without reason ...]. PMID- 8500715 TI - [Validation and clinical and epidemiological use of a serologic test recommended in the diagnosis of Helicobacter pylori infection]. AB - A commercial serologic test using purified antigens of Helicobacter pylori has been evaluated in the diagnosis of this infection. In a series of 250 patients undergoing endoscopy with antral biopsies for cytology, histology and culture, serology was positive in 68 of 71 patients with a positive culture (sensitivity: 96%) and negative in 67 of 69 patients with a normal mucosa and no microorganisms on biopsy (specificity: 97%). In the entire series, serology was positive in 33 patients with no infection on biopsies (13%). In a group of 205 blood donors, we confirmed an increasing prevalence with age, ranging from 13% in subjects less than 30 years old to 38% in subjects more than 60 years old. PMID- 8500716 TI - Effect of epidermal growth factor on gastric blood flow in rats: possible role in mucosal protection. AB - BACKGROUND: The mechanism by which epidermal growth factor (EGF) protects the gastric mucosa against injury is unclear. Whether EGF has any effect on gastric blood flow has not been reported. METHODS: Using an ex vivo gastric chamber preparation, the effect of EGF on gastric blood flow in rats was studied by laser Doppler flowmetry. Measurements of blood flow and mucosal damage were made in both intact and sialoadenectomized rats with graded doses of EGF at basal condition and after topical application of absolute ethanol. RESULTS: Sialoadenectomy alone increased ethanol-induced gastric mucosal lesions (P < 0.05) but had no significant effect on blood flow. EGF pretreatment resulted in both a reduction in ethanol-induced gastric mucosal injury as well as a significant increase in blood flow compared with controls (both P < 0.05). Graded doses of EGF (3.12-25 micrograms) resulted in an dose-dependent increase in gastric blood flow (r = 0.68; P < 0.001), which correlated inversely with the degree of mucosal damage (r = -0.72; P < 0.001). CONCLUSIONS: Mucosal protection by EGF is accompanied by an increase in gastric blood flow; this action may contribute to its mucosal protective effect. PMID- 8500717 TI - Effects of enteral nutrition and ethanol on cytochrome P450 distribution in small intestine of male rats. AB - BACKGROUND: Alcohol and nutrition are important factors regulating hepatic cytochrome P450 isozymes. The current studies were conducted to determine if intestinal P450 isozymes were similarly regulated. METHODS: Adult male Sprague Dawley rats were infused intragastrically with control or ethanol-containing diets. Western blot analysis was used to study CYP1A, CYP2B, and CYP3A isozymes in microsomes of three regions of the small intestine and liver. RESULTS: Compared with rats eating standard rat food, rats receiving the total enteral nutrition diet had reduced expression of several P450 isozymes in the intestine, especially in the jejunal region. Two CYP1A forms were detected by Western blot analysis in the small intestine with electrophoretic mobilities corresponding to hepatic CYP1A1 and CYP1A2. These forms appeared to be differentially regulated. Long-term ethanol treatment resulted in reduction of CYP3A and CYP1A apoprotein levels in the jejunal region. CONCLUSIONS: The P450 isozymes examined displayed differing intestinal distributions, responded to dietary manipulations, and were affected by ethanol treatment in a fashion not coordinated with that observed for hepatic isozymes. PMID- 8500718 TI - Sucrose: a novel permeability marker for gastroduodenal disease. AB - BACKGROUND: Nonsteroidal anti-inflammatory agents (NSAIDs) commonly cause asymptomatic gastroduodenal damage that may be clinically severe. At present the only method to determine the presence or absence of such damage is by invasive techniques such as endoscopy. Because distal small intestinal damage can be noninvasively detected with oral permeability tests, the hypothesis that gastroduodenal damage could be detected using similar methods was examined in the present study. RESULTS: Animal data are presented suggesting that sucrose represents an ideal probe molecule to detect increased gastroduodenal permeability in a site-specific manner. With gastroduodenal damage, caused by either ethanol or NSAIDs, sucrose permeability is increased. Furthermore, because sucrose is rapidly degraded within the small intestine, this probe does not detect small intestinal damage, making it specific for the upper gastrointestinal tract. Finally, a pilot study in humans is presented to show the use of this technique in evaluating human gastric permeability. CONCLUSIONS: Sucrose represents a novel permeability probe with specificity for damage of the upper gastrointestinal tract. In animals and humans it appears useful to noninvasively detect gastroduodenal injury caused by several agents. PMID- 8500719 TI - Is small intestinal permeability really increased in relatives of patients with Crohn's disease? AB - BACKGROUND: Patients with Crohn's disease have increased intestinal permeability, which may precede the development of clinical disease and be involved in disease pathogenesis. Subsequent studies have suggested that, as a group, first-degree relatives of patients with Crohn's disease do not have significantly increased small intestinal permeability rates. The present study proposes that conventional data analysis, used in these studies, may be inappropriate and has overlooked an important observation. METHODS: Lactulose and mannitol permeabilities were defined in healthy controls and in patients with Crohn's disease and their first degree relatives. RESULTS: Intestinal permeability in relatives was similar to that in the control group, but a subpopulation had abnormally high permeability rates in the absence of clinical evidence for disease. Raw data from another investigator confirmed this finding in an additional study; consequently, it is concluded that the original hypothesis is still viable. A small proportion of individuals, at high risk of developing Crohn's disease, have increased intestinal permeability. CONCLUSIONS: Increased intestinal permeability may precede clinical manifestations of Crohn's disease. PMID- 8500720 TI - p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. AB - BACKGROUND: The molecular basis of colorectal dysplasia and carcinoma arising in ulcerative colitis is poorly understood. Loss of heterozygosity involving the tumor suppressor gene p53 occurs frequently in neoplastic ulcerative colitis lesions. Point mutation affecting p53 is associated with loss of heterozygosity in other cancers. Therefore, it was determined whether p53 point mutation occurs in ulcerative colitis-associated neoplasia. METHODS: Single-strand conformation polymorphism analysis, DNA sequencing, and loss of heterozygosity studies were performed on 45 patients with ulcerative colitis-associated dysplasia and carcinoma. RESULTS: Point mutations were detected in 26 lesions from 20 patients, including 18 carcinomas, 6 dysplasia-associated masses, 1 flat dysplasia, and 1 lymph node metastasis. In two cases, identical p53 mutations were observed in both carcinoma and adjacent dysplasia. Missense mutations causing amino acid substitutions as well as nonsense mutations resulting in premature stop codons were seen. Tandem mutations, in which more than 1 sequence alteration occurred on the same allele of p53, were also detected. Point mutation was accompanied by loss of the other p53 allele in 8 of 10 patients informative for both loss of heterozygosity and mutation assays. CONCLUSIONS: These findings suggest that inactivation of p53 by mutation and loss of heterozygosity is a common mechanism of malignant transformation in ulcerative colitis. They also imply that in contrast to sporadic colorectal carcinoma, ulcerative colitis-associated neoplastic progression may involve p53 inactivation at relatively early, noninvasive stages. PMID- 8500721 TI - Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. AB - BACKGROUND: The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. METHODS: A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. RESULTS: There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. CONCLUSIONS: It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids. PMID- 8500722 TI - Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus. AB - BACKGROUND: A marked suppression of acetylcholine (ACh) release from myenteric nerves in the inflamed intestine of rats infected by Trichinella spiralis has been shown. In this model, there is increased expression of interleukin 1 beta (IL-1 beta) in the myenteric plexus. Therefore, the ability of IL-1 beta to alter ACh release in longitudinal muscle-myenteric plexus (LMMP) preparations from noninfected rats was examined. METHODS: LMMP preparations were loaded with [3H]choline before stimulation by KCl or electrical field stimulation. ACh release was recorded by measuring 3H in the superfusate. Experiments were performed in the presence or absence of human recombinant IL-1 beta. RESULTS: IL 1 beta had no immediate effect on the basal or stimulated release of ACh. A marked suppression of ACh release was observed in tissues that had been preincubated with IL-1 beta for 60 minutes or more. The effect of IL-1 beta was concentration and time dependent with maximum suppression occurring with 10 ng/mL of the cytokine after a 90-minute incubation. The action of human recombinant (hr) IL-1 beta was abolished by boiling the cytokine for 20 minutes and was prevented by preincubating the cytokine with neutralizing antibody. The IL-1 beta effect was also blocked by cycloheximide and was spontaneously reversible after 60 minutes. CONCLUSION: It was concluded that IL-1 beta suppresses ACh release via the formation and release of a protein mediator that could be another cytokine, including IL-1. Based on these findings, we consider IL-1 beta a putative mediator of the changes in cholinergic nerve function observed in the inflamed rat intestine. PMID- 8500723 TI - Antral G-cell and D-cell numbers in Helicobacter pylori infection: effect of H. pylori eradication. AB - BACKGROUND: It has recently been recognized that Helicobacter pylori infection is associated with abnormalities in the regulation of gastrin secretion. We investigated whether there was a relationship between H. pylori infection and G cell and D-cell numbers. METHODS: The numbers of antral G cells and D cells were compared between 20 patients with duodenal ulcer and 24 volunteers, 12 with and 12 without H. pylori infection. The effect of eradication of H. pylori infection on G-cell number was also evaluated. Antral mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of gastrin and somatostatin. RESULTS: The number of G cells was significantly (P < 0.02) less in patients with duodenal ulcer than in either infected or uninfected controls (3.7 +/- 0.3 vs. 6.2 +/- 0.6 and 5.3 +/- 0.5 G cells per gland for infected and uninfected controls, respectively). The ratio of G-cells to D-cells was similar in duodenal ulcer patients (2.2) and uninfected controls (2.0). It was found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, it is not associated with a change in the numbers of antral G cells or D cells in patients with duodenal ulcer. CONCLUSIONS: It is concluded that H. pylori infection-associated increase in gastrin secretion appear to be related to local factors regulating G-cell function. PMID- 8500724 TI - Evaluation of new occult blood tests for detection of colorectal neoplasia. AB - BACKGROUND: Hemoccult II, the guaiac-based fecal occult blood test used in most colorectal cancer screening programs, has an unsatisfactory sensitivity for asymptomatic colorectal neoplasms. We evaluated the relative performance of four fecal occult blood tests, directed against various components of the hemoglobin molecule. METHODS: All tests, Hemoccult II, HemoccultSENSA (a more sensitive guaiac test), HemeSelect (an immunochemical test specific for human hemoglobin), and HemoQuant (the heme-porphyrin assay), were performed by 107 patients with symptomatic colorectal cancer and 81 patients with predominantly asymptomatic adenoma. Hemoccult-SENSA and HemeSelect were performed by 1,355 screenees. RESULTS: HemeSelect and Hemoccult-SENSA had significantly higher sensitivity for colorectal cancer (97% and 94%, respectively) than the other tests. HemeSelect had the highest sensitivity for adenomas; in 45 patients with large (> or = 10 mm) adenomas, sensitivity was 76% for HemeSelect, 60% for HemoccultSENSA, and 42% for both Hemoccult and HemoQuant. In the screenees, estimated specificity was 97.8% for HemeSelect and 96.1% for Hemoccult-SENSA. CONCLUSIONS: HemeSelect and Hemoccult-SENSA have the highest levels of sensitivity for detection of colorectal neoplasia, but the immunochemical test HemeSelect provides the best combination of specificity and sensitivity. PMID- 8500725 TI - Small intestinal growth caused by feeding red kidney bean phytohemagglutinin lectin to rats. AB - BACKGROUND: Plant lectins are present in significant quantity in a variety of food sources. The aim of this study was to determine if they stimulated growth of the intestine. METHODS: Germ-free and conventional rats were pair fed purified phytohemagglutinin lectin (PHA) or equivalent casein in a fully nutritious diet. PHA was instilled into in situ jejunal and ileal loops. Organ weight, length, DNA, protein content, morphometry, and [3H]thymidine uptake into jejunal crypt cells were measured. RESULTS: A trophic response occurred in the small intestine (jejunum greater than ileum) because of PHA (P < 0.001), was sustained by continued exposure, and was reversible on reinstitution of the control diet (P < 0.05). The intestinal microbial flora in conventional animals that were fed PHA augmented the growth-stimulatory effects of PHA on intestinal weight (P < 0.01). PHA caused fecal protein, fat, and mucous glycoprotein levels (P < 0.001) to increase in germ-free animals. PHA increased jejunal mucosal crypt depth and crypt mitotic activity (P < 0.05); DNA content (P < 0.05) and [3H]thymidine uptake (P < 0.01) into crypt cells was increased. No increase in plasma or tissue content of gastrin, enteroglucagon, or peptide YY was observed on PHA exposure, and there was no increase in organ weight of the liver, kidney, or colon. CONCLUSIONS: PHA stimulated growth of rat small intestine when present in the diet or instilled in the bowel lumen. PMID- 8500726 TI - Regulation of canine gallbladder motility by brain peptides. AB - BACKGROUND: Brain peptides alter most gastrointestinal functions, but their effects on gallbladder motility have not been examined in detail. METHODS: Studies were conducted in awake, male beagle dogs. RESULTS: Of 30 brain peptides evaluated, thyrotropin-releasing hormone (TRH) and calcitonin gene-related peptide (CGRP) inhibited CCK- and meal-induced gallbladder contraction. These responses were abolished by ganglionic blockade. Truncal vagotomy prevented the central inhibitory action of TRH but not that of CGRP, whereas noradrenergic blockade prevented the central inhibitory action of CGRP but not that of TRH. Muscarinic blockade did not prevent the relaxing effect of cerebral TRH but pretreatment with the vasoactive intestinal peptide (VIP) antagonist, (4Cl-D-Phe6 Leu17)VIP, significantly attenuated gallbladder relaxation induced by cerebral TRH: the combination of both VIP and muscarinic antagonists abolished TRH-induced gallbladder relaxation. alpha-Adrenergic receptor blockade but neither beta adrenergic blockade nor adrenalectomy abolished gallbladder relaxation induced by cerebral CGRP. Intravenous infusion of VIP and norepinephrine inhibited CCK induced gallbladder contraction and these responses were abolished dose dependently by intravenous infusion of (4Cl-D-Phe6-Leu17)VIP and phentolamine, respectively. CONCLUSIONS: Cerebral TRH inhibits canine gallbladder contraction by stimulation of vagal outflow and subsequent release of VIP acting via its specific receptor whereas cerebral CGRP inhibits gallbladder contraction by stimulation of sympathetic, noradrenergic outflow via alpha-adrenergic receptors. PMID- 8500727 TI - Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium. AB - BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally. PMID- 8500728 TI - Altered small intestinal smooth muscle function in Crohn's disease. AB - BACKGROUND: Studies in animals indicate that inflammation causes changes in smooth muscle contractility. Because Crohn's disease is associated with altered motility, this study investigated the contractility of intestinal muscle resected from patients with or without Crohn's disease. METHODS: The isometric contraction of muscle strips from the small bowel of 36 patients with and 24 patients without Crohn's disease was examined. RESULTS: In longitudinal muscle from patients with Crohn's disease, there was a 55% increase in maximum contraction induced by carbachol but not histamine, but there was no change in the 50% effective dose (ED50) for these agonists. In contrast, in circular muscle from patients with Crohn's disease there was a sevenfold decrease in the ED50 value for carbachol but no change in maximum contraction. There was a 2.5-fold increase in the maximum response to histamine, but no change in ED50, in circular muscle from patients with Crohn's disease. However, there was no change in KCl-induced contraction between the two groups. The carbachol responses were atropine sensitive. Histamine responses were blocked by the H1 antagonist mepyramine but were not altered by a diamine oxidase inhibitor. All responses were tetrodotoxin insensitive. CONCLUSION: These results show altered receptor-mediated contraction in small intestinal muscle in patients with Crohn's disease. PMID- 8500729 TI - Rat duodenal iron-binding protein mobilferrin is a homologue of calreticulin. AB - BACKGROUND: Mobilferrin is a water soluble 56-kilodalton protein isolated from human and rat duodenal mucosa. It binds iron and other transitional metals in vivo and in vitro and is postulated to play a role in their absorption and intracellular metabolism. The purpose of this study was to characterize mobilferrin. METHODS: Mobilferrin was characterized by identification of the N terminal amino acid sequence, two-dimensional protein electrophoresis, and studies of mobilferrin and homologues using anti-mobilferrin antibody and competitive metal binding. RESULTS: The N-terminal amino acid sequence of mobilferrin was Asp-Pro-Ala-Ile-Tyr-Phe-Lys-Glu-Gln-Phe-Leu-Asp-Gly-Asp-Ala-Ser Thr- and is a homologue of calreticulin (calregulin). The proteins had a similar molecular mass (56 kilodalton) and isoelectric point (4.7). Anti-mobilferrin antibodies react with calreticulin. Both proteins bind iron and calcium but have a greater affinity for iron. CONCLUSIONS: Mobilferrin and calreticulin are homologues that bind iron with greater affinity than calcium and other transitional metals. Competitive binding of metals by mobilferrin provides insight into the absorptive pathway shared by both essential and toxic transitional metals. PMID- 8500730 TI - Extracellular matrix composition influences insulinlike growth factor I receptor expression in rat IEC-18 cells. AB - BACKGROUND: The composition of the extracellular matrix (ECM) as well as insulinlike growth factor I (IGF-I) receptor density vary along the crypt-villus axis. We determined whether components of the ECM influence IGF-I receptor expression in IEC-18 rat small intestine crypt cells. METHODS: IEC-18 cells were cultured on plastic, collagen type IV, Matrigel, and laminin at the plateau and proliferative growth phases. Receptor affinity (Kd) and number (Bmax) were determined by competitive binding of 125I-IGF-I in the presence of increasing concentrations of unlabeled IGF-I. Receptor isolation was performed by affinity cross linking. Messenger RNA (mRNA) for IGF-I receptor was quantified by Northern analysis. RESULTS: Specific binding of IGF-I > IGF-II > insulin was observed. A 130,000-molecular weight protein was identified by cross-linking, consistent with the alpha subunit of the IGF-I receptor. Scatchard analysis revealed no effect of ECM on IGF-I binding affinity. In contrast, the Bmax was 18% lower for plateau phase cells cultured on Matrigel vs. plastic and was 42% lower for cells cultured on laminin vs. collagen type IV. The Bmax for proliferative growth phase cells was decreased when cultured on Matrigel vs. plastic and was 10-fold less than for cells cultured at the plateau growth phase. Northern analysis revealed that IEC 18 cells cultured on Matrigel had less mRNA for IGF-I receptor than cells cultured on plastic. CONCLUSIONS: The rate of cell proliferation and the composition of the ECM influence IGF-I receptor expression in IEC-18 cells. PMID- 8500731 TI - Leucine and phenylalanine kinetics in compensated liver cirrhosis: effects of insulin. AB - BACKGROUND: The pathogenesis of the altered ratio of branched-chain amino acid to aromatic amino acid concentration in liver cirrhosis is poorly known. We explored the possible link between altered amino acid concentrations and kinetics in cirrhosis. METHODS: Post-absorptive leucine and phenylalanine rates of appearance (Ra) and their response to insulin were studied in patients with compensated, nondiabetic cirrhosis and in controls. RESULTS: In the cirrhotics, concentration of postabsorptive phenylalanine was greater and that of alpha-ketoisocaproate lower than in controls, whereas concentration of leucine was comparable. Leucine Ra was lower, phenylalanine Ra was greater, and the ratio of leucine Ra to phenylalanine Ra was markedly decreased (P < 0.001) in patients vs. controls (2.40 +/- 0.23 vs. 3.67 +/- 0.19, respectively). During an euglycemic hyperinsulinemic clamp, glucose disposal was reduced and leucine Ra was suppressed more profoundly in cirrhotics than in controls, whereas suppression of phenylalanine Ra was comparable. CONCLUSIONS: In compensated liver cirrhosis, postabsorptive phenylalanine Ra is increased with respect to leucine Ra, suggesting the existence either of altered amino acid pools and/or transport or of abnormally sequenced proteins and/or peptides. Insulin resistance is restricted to glucose, but not to amino acid metabolism. PMID- 8500732 TI - Bacterial translocation in the portal-hypertensive rat: studies in basal conditions and on exposure to hemorrhagic shock. AB - BACKGROUND: Portal hypertension is associated with altered intestinal motor and mucosal function. The aim of this study was to determine whether portal hypertension, per se, or in association with acute hemorrhagic shock, predisposes to the translocation of bacteria across the intestine. METHODS: Translocation to both mesenteric lymph nodes and blood was compared in three groups of rats: portal-hypertensive (single-stage calibrated stenosis of portal vein), sham operated, and unoperated controls. Half of the animals in each group were exposed to hemorrhagic shock. RESULTS: In the basal state, translocation to both mesenteric lymph nodes (portal hypertension vs. sham vs. controls, 411.5 +/- 119 vs. 151.1 +/- 42.6 vs. 18.1 +/- 12.6 colony-forming units [CFU]/g; P < 0.05) and blood (portal hypertension vs. sham vs. controls, 100% vs. 30% vs. 0% positive blood cultures; P < 0.05) was significantly increased in the portal-hypertensive animals. Furthermore, translocation was strikingly increased in these animals after hemorrhagic shock (mesenteric lymph node cultures, portal hypertension vs. portal hypertension with shock, 411 +/- 119 vs. 1018.2 +/- 372.2 CFU/g; P < 0.05). CONCLUSIONS: Portal hypertension promotes bacterial translocation, especially in relationship to acute hemorrhage. These findings may, in part, explain the susceptibility of patients with liver disease to sepsis of enteric origin. PMID- 8500733 TI - Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. AB - BACKGROUND: Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS: Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS: All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS: TPGS (20-25 IU.kg-1.day 1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis. PMID- 8500734 TI - The endothelin-1 binding site in rat liver tissue: light- and electron microscopic autoradiographic studies. AB - BACKGROUND: Endothelin (ET) is known as a vasoconstrictive substance. The receptors for ET have been shown in various organs. However, little is known about the endothelin-1 (ET-1) binding sites in the liver. The aim of this study was to examine ET-1 binding sites in the liver. METHODS: ET-1 binding sites in rat liver were studied in vivo by light- and electron-microscopic autoradiography using 125I-ET-1. RESULTS: Light-microscopic autoradiographic observation revealed strong localization of grains in the sinusoidal lining cells of the hepatic lobule and a small number of grains in the luminal space of the portal vein and central vein. In the hepatic lobule, more grains were located in the periportal region, and the quantity tended to decrease from the midzonal to the pericentral region. Electron-microscopic autoradiographic observation revealed grains in Ito cells and in the endothelial cells of the portal vein, central vein, and hepatic sinusoids. CONCLUSIONS: These results suggest that ET-1 acts on Ito cells and on endothelial cells of the hepatic sinusoids, portal vein, and central vein and that its action is related to hemodynamics of the liver, particularly regulation of the microcirculation of the hepatic sinusoids. PMID- 8500735 TI - The nature and prognosis of severe cryptogenic chronic active hepatitis. AB - BACKGROUND: Cryptogenic chronic active hepatitis may be an autoimmune or viral disease. Our aims were to determine the clinical features, human leukocyte antigen phenotype, and response to corticosteroid therapy of severe cryptogenic chronic active hepatitis and to compare it with these other diseases. METHODS: Twelve patients with cryptogenic hepatitis were compared with 94 patients with autoimmune hepatitis and 30 patients with chronic viral hepatitis. RESULTS: Patients with cryptogenic hepatitis were indistinguishable from those with autoimmune hepatitis by age, gender, and individual laboratory and histological findings. HLA B8 (75% vs. 49%, P = 0.2), DR3 (71% vs. 51%, P = 0.5), and A1-B8 DR3 (57% vs. 38%, P = 0.6) occurred as commonly in each group. Patients with cryptogenic hepatitis entered remission (83% vs. 78%, P > 0.9) and failed treatment (9% vs. 11%, P > 0.8) as frequently as those with autoimmune hepatitis during corticosteroid therapy. In contrast, patients with chronic viral hepatitis had lower biochemical abnormalities, less frequent multilobular necrosis at presentation, and different human leukocyte phenotypes than those with cryptogenic or autoimmune disease. CONCLUSIONS: Severe cryptogenic hepatitis has a clinical expression, genetic phenotype, and corticosteroid responsiveness that is similar to autoimmune hepatitis. It may be an autoimmune disorder that has escaped detection by conventional immunoserological markers. PMID- 8500736 TI - The effect of chloroquine administration on two experimental models of acute pancreatitis. AB - BACKGROUND: Recent experimental findings have suggested that activation of trypsinogen by cathepsin B within acidic pancreatic acinar cell cytoplasmic vacuoles may be a critical early event in both secretagogue and diet-induced pancreatitis. The weak base chloroquine accumulates within acidic intracellular compartments, raises their pH, and can inhibit proteolysis as well as cathepsin B. METHODS: We have investigated the effect of in vivo chloroquine administration on both secretagogue and diet-induced experimental pancreatitis to determine if raising the pH of cytoplasmic vacuoles in these models of pancreatitis would have a protective effect. RESULTS: Infusion of chloroquine (5 mg.kg-1.h-1) resulted in the uptake and concentration of chloroquine in the pancreas, an increase in the pH of acinar cell acidic compartments, and interference with the pH-dependent sorting of lysosomal hydrolases from digestive enzyme zymogens. However, chloroquine administration did not have a protective effect against the hyperamylasemia, the pancreatic edema, the morphological changes or the mortality that is associated with these models of pancreatitis. CONCLUSIONS: These observations lead us to conclude that raising the pH of acinar cell acidic compartments by in vivo administration of chloroquine does not prevent either secretagogue or diet-induced pancreatitis. PMID- 8500737 TI - Two mechanisms of inhibition by bile on luminal feedback regulation of rat pancreas. AB - BACKGROUND: Pancreatic exocrine secretion in conscious rats is regulated by luminal protease activities. A decrease in protease activities results in pancreatic hypersecretion (luminal feedback regulation). Although bile has been known to affect this regulation, the mechanism is not clear. In the present study, the effect of bile in the intestinal lumen on luminal feedback regulation was examined. METHODS: Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. Because the rate of enzyme secretion varies in individual rats, porcine trypsin was infused instead of pancreatic juice. Graded doses of porcine trypsin were infused with bile or Tris buffer containing 10 mmol/L CaCl2 instead of bile. RESULTS: The trypsin activities in the proximal quarter of the small intestine were similar in rats infused with bile and with Tris buffer containing 10 mmol/L CaCl2 (without bile); however, increments of pancreatic secretions of fluid and protein were significantly higher in rats without bile infusion than in those with bile infusion. Infusion of calcium-free Tris buffer resulted in significantly lower trypsin activity. CONCLUSIONS: The results indicate that bile has two inhibitory mechanisms on pancreatic secretion, one stabilizing luminal trypsin, the other independent of luminal trypsin activity. PMID- 8500738 TI - Cholesterol and bile acid biodynamics after total small bowel resection and bile diversion in humans. AB - BACKGROUND: In humans, the patterns of cholesterol and bile acid biodynamics in the absence of the small intestine are not yet known. They are described in two parenterally fed patients several months after total enterectomy and bile diversion. METHODS: After an intravenous pulse of [3H]cholesterol, a long-term study involved the analysis of both the decay in the specific activity of plasma cholesterol and the biliary outputs of sterols and bile acids. RESULTS: Plasma cholesterol input reached 2-3 g/day (vs. 1 g/day in healthy patients), mostly from synthesis. As assessed by sterol balance, whole body cholesterol synthesis approximated 6 g/day (vs. 0.6-0.8 g/day). Unusually, about 60% of the newly synthesized cholesterol was eliminated, without prior transit into the bloodstream, from the liver into the bile. Bile acid conversion concerned over 90% (vs. 40%-50%) of the cholesterol meant to be excreted, issued from plasma or hepatic synthesis. In addition to cholic and chenodeoxycholic acids, one patient secreted up to 1 g/day of 7-epicholic acid. CONCLUSIONS: The stimulation (up to 10-fold) of the cholesterol and bile acid synthesis, stronger than that observed following ileal bypass or resection or complete bile diversion, could well be partially linked to the absence of small bowel tissue per se. PMID- 8500739 TI - Gallstone cholesterol content is related to apolipoprotein E polymorphism. AB - BACKGROUND: The genetically determined phenotypes of apolipoprotein E are related to variations in lipoprotein levels and in the enterohepatic metabolism of cholesterol and bile acids. The present study was designed to elucidate the role of apolipoprotein E polymorphism in gallstone formation. METHODS: Apolipoprotein E phenotype was determined in 169 consecutive cholecystectomy patients and in 200 controls. The cholesterol content of the gallstones (n = 169), the presence of cholesterol monohydrate crystals of fresh gallbladder bile (n = 142), and the nucleation time (n = 35) were also analyzed. RESULTS: The median cholesterol content of the gallstones was higher in the apolipoprotein E4 category (phenotypes E4/4 and E4/3, 97%) than in the E3 (E3/3, 78%) and E2 patients (E2/2 and E2/3, 76%, P = 0.0003). In E4 patients, cholesterol crystals were found immediately after surgery in 27 of 40 (68%), whereas in E3 and E2 groups in 36 of 88 (41%), and 4 of 14 (29%) of the patients (P = 0.0001). The median nucleation time in E4 patients (2.5 days) was shorter than in patients with E3 (5.5 days) or E2 (6.0 days) (P = 0.0016). CONCLUSIONS: These data indicate that apolipoprotein E polymorphism affects cholesterol content of cholelithiasis. We suggest that this phenomenon is mediated by the altered formation of cholesterol monohydrate crystals in different apolipoprotein E phenotypes. PMID- 8500740 TI - Acute relapsing pancreatitis as a complication of papillary stenosis after endoscopic sphincterotomy. AB - Endoscopic sphincterotomy has proven to be a safe alternative to surgery for selected types of biliary disease. Despite a relatively low morbidity, postprocedure complications are well described. This report presents an experience with three patients in whom acute relapsing pancreatitis developed as a possible complication of papillary stenosis after endoscopic sphincterotomy. None of the patients had a previous history of elevations in serum amylase levels before endoscopic sphincterotomy. After procedure, pancreatitis and subsequently acute relapsing pancreatitis with documented stricture of the pancreatic duct orifice developed in all three patients. After surgical transduodenal sphincteroplasty, no new episodes of acute relapsing pancreatitis occurred. PMID- 8500741 TI - Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor. AB - Chronic hepatitis B virus (HBV) infection is still a major cause of liver disease for which no definite therapy is available. We describe here a hepatitis B surface antigen (HBsAg) carrier patient with active viral replication (HBV DNA positive) who was treated for leukemia by bone marrow transplantation (BMT) from an HBV immune donor. Following BMT from the antibody to hepatitis B core antigen (anti-HBc) positive/anti-HBs positive bone marrow donor, immune reconstitution of the recipient's bone marrow resulted in clearance of the circulating HBsAg, as well as HBV DNA. The patient acquired immunity against HBV, which lasted for more than 8 months posttransplantation. Therefore, this report provides evidence that adoptive transfer of specific immunity against HBV through allogeneic BMT may lead to clearance of persistent HBV infection. Furthermore, the data support the hypothesis that the HBsAg carrier state is most probably the result of an inefficient immune response against HBV, implying that clearance of HBV may be facilitated by adoptive cellular immunotherapy. PMID- 8500742 TI - Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients. AB - Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia. PMID- 8500743 TI - Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. AB - BACKGROUND: It is not widely appreciated that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the duodenum. We reviewed the adverse effects of NSAIDs on the large and small intestine, the clinical implications and pathogenesis. METHODS: A systematic search was made through Medline and Embase to identify possible adverse effects of NSAIDs on the large and small intestine. RESULTS: Ingested NSAIDs may cause a nonspecific colitis (in particular, fenemates), and many patients with collagenous colitis are taking NSAIDs. Large intestinal ulcers, bleeding, and perforation are occasionally due to NSAIDs. NSAIDs may cause relapse of classic inflammatory bowel disease and contribute to serious complications of diverticular disease (fistula and perforation). NSAIDs may occasionally cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs, however, frequently cause small intestinal inflammation, and the associated complications of blood loss and protein loss may lead to difficult management problems. The pathogenesis of NSAID enteropathy is a multistage process involving specific biochemical and subcellular organelle damage followed by a relatively nonspecific tissue reaction. The various possible treatments of NSAID-induced enteropathy (sulphasalazine, misoprostol, metronidazole) have yet to undergo rigorous trials. CONCLUSIONS: The adverse effects of NSAIDs distal to the duodenum represent a range of pathologies that may be asymptomatic, but some are life threatening. PMID- 8500744 TI - Permeability in Crohn's disease: altered barrier functions in healthy relatives? PMID- 8500745 TI - Fecal occult blood tests: what's new? PMID- 8500746 TI - Laser photoablation of Barrett's epithelium: burning issues about burning tissues. PMID- 8500747 TI - Differences in amino acid kinetics in cirrhosis. PMID- 8500748 TI - Hepatoprotective properties of ursodeoxycholic acid. PMID- 8500749 TI - The gastrin (or is it CCK-B?) receptor on the parietal cell is cloned. PMID- 8500750 TI - 10 g of fat per day may keep gallstones away. PMID- 8500751 TI - Biliary acidification and gallstone calcification. PMID- 8500752 TI - Renal effects of amino acid administration in cirrhosis. PMID- 8500753 TI - Animal models for Helicobacter pylori. PMID- 8500754 TI - Immunoproliferative small intestinal disease or celiac disease. PMID- 8500755 TI - Regulation of canine gastric mucin synthesis and phospholipid secretion by acid secretagogues. PMID- 8500756 TI - The timing of p53 inactivation in chronic ulcerative colitis. PMID- 8500757 TI - Thromboxanes, indomethacin, and experimental colitis. PMID- 8500758 TI - Intergenic sequences from the heat-shock protein 83-encoding gene cluster in Leishmania mexicana amazonensis promote and regulate reporter gene expression in transfected parasites. AB - Regulation of expression from hsp83 gene cluster encoding heat-shock protein (HSP) 83 of the protozoan parasite Leishmania mexicana amazonensis (L.m.a) was examined. The first gene from this cluster, along with 8 kb of flanking sequences, was cloned, and intergenic region (IR) sequences were found upstream from the cluster. L.m.a. parasites were electroporated with a plasmid (pICI) in which the chloramphenicol acetyltransferase (CAT)-encoding gene (cat) was cloned between two IRs derived from an internal repeat unit of the hsp83 cluster, resulting in CAT activity at 26 degrees C. Exposure of cells transfected with this plasmid to a 35 degrees C heat shock led to an increase in CAT activity, within a range similar to that observed for the accumulation of hsp83 steady state mRNA at 35 degrees C. S1 analysis of the hsp83 mRNA showed that the major part of the IR was transcribed and mostly present as 3' non-translated extensions. Deletion analysis of the flanking regions indicated that the presence of IR sequences, both upstream and downstream from cat, was critical to its expression. Partial deletions that removed the original AG splice acceptor site (leaving 289 bp upstream) and downstream IR sequences (leaving 200 bp) did not eliminate CAT activity. However, this combined deletion altered the effect of temperature on cat expression in transfected cells, as compared with the activity measured in cells transfected with the original plasmid. PMID- 8500759 TI - Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms. AB - The biliary glycoprotein (BGP)-encoding gene is a member of the human carcinoembryonic antigen (CEA) gene family. We have now cloned several mouse Bgp cDNAs from an outbred CDR-1 mouse colon cDNA library, as well as by reverse transcription-PCR amplification of colon RNA. The distinguishing features of the deduced Bgp protein isoforms are found in the two divergent N-terminal domains, the highly conserved internal C2-set immunoglobulin domains, and an intracytoplasmic domain of either 10 or 73 amino acids (aa). The cDNA structures suggest that these mRNAs are produced through alternative splicing of a Bgp gene and the usage of multiple transcriptional terminators. The Bgp deduced aa sequences are highly homologous to several well characterized rat hepatocyte proteins such as the cell CAM105/ecto-ATPase/pp120/HA4 proteins. Oligodeoxyribonucleotide probes representing the various cDNA isoform domains revealed predominant transcripts of 1.8, 3.1 and 4.0 kb on Northern analyses of mouse colon RNA; some of these bands are actually composed of several co migrating transcripts. The transcripts encoding the long intracytoplasmic-tailed Bgp proteins are expressed at one-tenth the relative abundance of the shorter tailed species. We have previously demonstrated that several mouse Bgp cDNAs, when transfected into eukaryotic cells, express BGP proteins at the cell surface and function in vitro as cell adhesion molecules, much like their human and rat counterparts. The expression of the many Bgp isoforms at the surface of epithelial cells, such as colon, suggests that these proteins play a determinant role, through self- or heterologous contact, in renewal and/or differentiation of their epithelia. PMID- 8500760 TI - Functional starch-binding domain of Aspergillus glucoamylase I in Escherichia coli. AB - We have fused three starch-binding domains (SBD) encoding gene fragments (residues 511-616, 495-616 and 481-616) of glucoamylase I (GAI) to the 3' end of the Escherichia coli malE gene encoding maltose-binding protein (MBP). The fusion proteins were produced in E. coli and were purified by chromatography on cross linked amylose. Factor Xa digestion of the fusion proteins resulted in the release of functional SBD fragments which were separated from MBP on the basis of their differential binding to cross-linked amylose. The amino acid (aa) composition of the purified SBD fragments agreed with the respective amino acid compositions of GAI. The sizes of the SBD fragments were 11.9, 13.8 and 15.6 kDa, respectively. PMID- 8500761 TI - Construction of a UMP synthase expression cassette from Dictyostelium discoideum. AB - We have prepared a DNA cassette containing the UMP synthase (UMPS)-encoding gene (PYR5-6) from Dictyostelium discoideum. This gene contains no introns and can be used for expression of the UMPS protein. Due to the high percentage of AT in the flanking regions, useful restriction sites were absent, therefore the PYR5-6 was subcloned as three separate parts, manipulated, and religated to make a full length clone. After reconstructing the coding region, we examined its functionality by introducing this gene under the control of the yeast GAL1 promoter into several uracil-requiring mutants of Saccharomyces cerevisiae. These studies demonstrated that the reconstructed PYR5-6 gene was functional and could complement independent ura3 and ura5 mutations in yeast. PMID- 8500762 TI - Cloning of the Eh cdc2 gene from Entamoeba histolytica encoding a protein kinase p34cdc2 homologue. AB - To understand better growth regulation in the protozoan parasite, Entamoeba histolytica (Eh), a homologue of the cdc2 gene encoding the yeast cyclin dependent protein kinase, p34cdc2, has been cloned and sequenced. This gene, called Eh cdc2, contains a 79-bp intron located in the same place as the second of four introns in the Schizosaccharomyces pombe cdc2 gene. The sequence of an Eh cdc2 cDNA confirms the conserved eukaryotic splice donor (GT) and acceptor (AG) sites and shows that Eh is able to splice mRNAs. The spliced Eh cdc2 open reading frame is 291 amino acids (aa) long, encoding an M(r) 33,806 protein. The primary sequence of Eh cdc2 is most like those of cdc2 homologues Eg1 of Xenopus laevis and CDK2 of man (52% aa identity with each) and codes for (i) the serine (Ser), threonine (Thr), and tyrosine residues phosphorylated in p34cdc2 proteins, (ii) 32 of 33 aa conserved in other Ser/Thr protein kinases, and (iii) the sequence PVTSVRE instead of PSTAIRE found in most p34cdc2 proteins. This is the first cell division-cycle regulatory protein homologue, as well as the first intron identified from Eh. PMID- 8500763 TI - Common sequence elements are important for transcription and replication of the extrachromosomal rRNA-encoding genes of Tetrahymena. AB - Three types of conserved sequence elements have previously been identified in the generally non-conserved, 5' non-transcribed spacer region of the rRNA-encoding gene (rDNA) of Tetrahymena species. In vivo and in vitro experiments have identified the start point (tsp) for rDNA transcription. Comparative sequence analysis suggested that the type-I sequence element was likely to function as the promoter for rDNA transcription. We have used in vitro transcription assays to demonstrate that sequences in the 3' half of the type-I repeat located proximal to the tsp are essential for the accurate initiation of rRNA synthesis. These sequences define the 5' boundary of the core or minimal promoter element and include the sequences which function in rDNA replication and maintenance in the homologous regions in two upstream type-I sequence elements. These sequences may bind factors important for both the transcription and replication of rDNA. PMID- 8500764 TI - Cloning and expression of the gene encoding Acacia confusa trypsin inhibitor that is active without post-translational proteolysis. AB - A recombinant plasmid containing the coding regions for Acacia confusa trypsin inhibitor (ACTI) has been constructed and expressed in Escherichia coli cells, as a fusion protein between ACTI and glutathione S-transferase (GST). The GST-fusion was produced as a soluble protein which did not require denaturing agents such as urea to solubilize it. The recombinant ACTI (reACTI) was obtained by treating the GST-fusion protein with thrombin. Both the reACTI and fusion protein have a strong inhibitory effect on trypsin activity without post-translational proteolysis. PMID- 8500765 TI - Tobacco mosaic virus infection of transgenic Nicotiana tabacum plants is inhibited by antisense constructs directed at the 5' region of viral RNA. AB - Antisense (AS) versions of two 51-nucleotide (nt) sequences near the 5' end of tobacco mosaic virus (TMV) RNA have been shown to inhibit in vitro translation of the adjacent gene that encodes both the 126- and 183-kDa proteins. These DNA fragments have been cloned into the binary vector, pMON530, such that either the nopaline synthase (Nos) promoter or cauliflower mosaic virus (CaMV) 35S RNA promoter is used to drive synthesis of the corresponding sense and AS RNAs. Transgenic Nicotiana tabacum cv. Xanthi nn plants containing these constructs were challenged with TMV. Plants expressing the AS orientation of a 51-nt TMV leader sequence, under the control of the CaMV 35S promoter, were found to be resistant to infection when inoculated with up to 100 times the concentration of TMV which produced severe infections in control plants. Systemic accumulation of TMV RNA and progeny virus was diminished 15 to 30-fold in these plants. Accumulation of the viral coat protein was diminished 6 to 7-fold implying a selective inhibition of TMV replication. PMID- 8500766 TI - Localization of adjacent binding domains for cellular proteins over the minute virus of mice P4 promoter by site-specific photoaffinity labelling. AB - A photoaffinity labelling (PHL) procedure was used to localize the specific binding sites for A92L fibroblast nuclear proteins on the minute virus of mice (MVM) P4 promoter. We describe a chemical and biochemical method for the construction of precisely modified photoreactive (phr) DNA probes. In this method, a phenylazide group is attached to the DNA fragment by coupling SASD [sulfosuccinimidyl-2-(p-azidosalicyl-amido)ethyl-1,3'-dithiopro pio nate] to the primary amino group of the linker arm present at any predetermined position. These phr probes would identify, upon photocrosslinking, only those proteins which bind to the location of the phr group. Specifically, two phr probes representing the 139-172 bp region of the MVM P4 promoter were constructed in which the highly phr phenylazide group was attached with a linker at nucleotide 168, towards the side of the GC box proximal to the TATA box. The PHL studies with these photoprobes revealed that although the proteins of 95 and 120-kDa bind near nt 168 of the P4 promoter, the 120-kDa protein requires the region between the TATA box and the GC box for binding to the MVM P4 promoter. PMID- 8500767 TI - Identity of a major 3-deoxyglucosone-reducing enzyme with aldehyde reductase in rat liver established by amino acid sequencing and cDNA expression. AB - We have purified a rat liver enzyme that catalyzes the NADPH-dependent reduction of 3-deoxyglucosone (3-DG), a major intermediate in the Maillard reaction and a potent cross-linker responsible for the polymerization of proteins. Comparison of the amino acid (aa) sequences of nine peptides obtained from the rat 3-DG reducing enzyme by lysylendopeptidase digestion with the aa sequence of human aldehyde reductase (ALR) [Bohren et al., J. Biol. Chem. 266 (1991) 24031-24037] strongly suggested that the purified enzyme was rat ALR. We cloned the cDNA encoding ALR from a rat kidney cDNA library using a human ALR cDNA fragment, amplified by polymerase chain reaction, as a probe. All nine peptides identified in the purified rat 3-DG-reducing enzyme were found in the aa sequence deduced from the rat ALR cDNA. Moreover, cell extract from COS-1 cells transfected with the rat ALR cDNA exhibited NADPH-dependent 3-DG-reducing activity and cross reacted with antiserum raised against the purified rat 3-DG-reducing enzyme. All the above data indicate clearly that the 3-DG-reducing enzyme is identical with ALR. Northern blot analysis of total mRNA from a variety of rat tissues showed fairly high levels of expression of ALR mRNA. This suggests that sufficient ALR is present to detoxify 3-DG when it is formed through the Maillard reaction in vivo. PMID- 8500768 TI - Regulation of expression of the gene encoding human acid beta-glucosidase in different cell types. AB - Acid beta-glucosidase (beta Glc) activity and mRNA levels were measured in several human cell lines, and found to vary over 50-fold. A comparison between relative levels of beta Glc enzyme and mRNA levels revealed three patterns. The first group, including epithelial, lymphoblast, histiocyte, glioblastoma and astrocytoma cell lines, showed a direct relationship between relative levels of mRNA and enzyme activity, indicating that mRNA levels play an important role in determining enzyme activity. The second group, including fibroblast, promyelocyte and neuroglioma cell lines, also showed a direct relationship between beta Glc enzyme and mRNA levels within this group, but had enzyme activities that were approximately sixfold higher than expected, when compared with enzymes within the first group. The third pattern was exhibited by a single monocyte cell line, which showed high levels of beta Glc mRNA, but only intermediate levels of enzyme activity. These results suggest that although beta Glc mRNA levels play a major role in regulating beta Glc activity, other mechanisms also influence enzyme levels in certain cell lines. These results also demonstrate the importance of examining several different cell types when considering mechanisms of housekeeping gene regulation. Additionally, culturing cells in the presence of the beta Glc-specific inhibitor, conduritol-B-epoxide, did not affect beta Glc mRNA levels, and cells derived from normals had levels of beta Glc mRNA comparable to those from Gaucher disease patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500769 TI - The complete sequences of plasmids pFNeo and pMH-Neo: convenient expression vectors for high-level expression of eukaryotic genes in hematopoietic cell lines. AB - The eukaryotic expression vector, pFNeo, confers resistance to the antibiotic G418 and directs hematopoietic-specific expression of proteins under the control of the long terminal repeat from the Friend spleen focus-forming virus. Here, we report the entire nucleotide sequence of pFNeo. We have also constructed and sequenced a pFNeo-based expression vector (pMH-Neo) that carries an improved multiple cloning site region for easier subcloning. The utility of both vectors was demonstrated by transfection of murine T-cell hybridomas by electroporation. Transfection with either pFNeo or pMH-Neo yielded a high frequency (1 in 2 x 10(4)) of G418-resistant cell lines. PMID- 8500770 TI - Sequence determination of variable region genes of two human monoclonal antibodies against Neisseria meningitidis. AB - Nucleotide sequences for the variable regions of both the heavy and light chains for two human monoclonal antibodies have been determined. Both antibodies are directed against an outer membrane protein of Neisseria meningitidis, and their genes show a low resemblance to germline sequences. PMID- 8500771 TI - The human ribosomal protein S6 gene: isolation, primary structure and location in chromosome 9. PMID- 8500772 TI - A nursing home bill of rights. PMID- 8500773 TI - Fluoroquinolones: how to use (but not overuse) these antibiotics. AB - The fluoroquinolone antibiotics are relatively new agents with long serum half lives, a high degree of bioavailability, and a broad spectrum of activity against many gram-negative and some gram-positive organisms. They are useful in a range of clinical settings but should not be considered as first-line treatment of many infections. Specific indications include chronic osteomyelitis caused by multiple resistant gram-negative bacilli, chronic bacterial prostatitis refractory to other oral antibiotics, complicated urinary tract infections, and empiric therapy of suspected bacterial GI infections. Quinolones may also be considered when patients are allergic to a conventional agent, when infections are caused by multiple-resistant gram-negative bacilli, or when the toxicity of an alternate therapy is greater. PMID- 8500774 TI - The cataract revolution: what the primary care physician needs to know. AB - Older patients often come first to their primary care physicians with complaints of blurred vision associated with cataracts. An initial office-based diagnosis includes a simple patient history and examination of the retina with an ophthalmoscope. Early referral for an ophthalmologic examination is recommended. Deciding which patients are candidates for surgery depends largely on the cataract's impact on individual lifestyle and ability to function. Patients should be informed of the risks and benefits of surgery as well as some measures that may delay the need for it. Postsurgical complications, although uncommon, require immediate diagnosis and treatment. PMID- 8500775 TI - HIV infection in older patients: when to suspect the unexpected. AB - The number of AIDS patients over age 60 has risen steadily in the past decade. The number of transfusion-acquired AIDS cases probably has peaked--or will soon peak. Homosexual (or bisexual) behavior remains the predominant risk factor for AIDS until the seventh decade. Disease progression appears to be more rapid in the elderly, although the observed shorter survival time may result from a delay in diagnosis. Symptoms of HIV infection are often nonspecific, such as fatigue, anorexia, weight loss, and decreased physical and cognitive function. The five most common opportunistic infections in older HIV-infected patients are Pneumocystis carinii pneumonia, tuberculosis, Mycobacterium avium complex, herpes zoster, and cytomegalovirus. A number of features of HIV-related dementia may help to distinguish it from Alzheimer's disease. PMID- 8500776 TI - Identification of the product of tetP gene: a possible mechanistic basis for tetracycline resistance in Clostridium perfringens. AB - Using cloning and in vitro protein synthesis we identified the polypeptide product of the tetP gene of Clostridium perfringens which is responsible for conferring resistance to tetracycline. Two EcoRI fragments invariably share the resistance determinant in all of the Clostridium perfringens isolates that we studied. Likewise, two proteins of 10 and 20 kDa were found to be conserved in all of the recombinant clones. The 10 kDa protein appears to be responsible for the constitution of the expression of tetP gene in C. perfringens. PMID- 8500777 TI - Sporulation and synthesis of extracellular proteinases in Bacillus subtilis are more temperature-sensitive than growth. AB - Bacillus subtilis 115 grew in a medium with amino acids and glucose with the maximum specific growth rates mu of 1.20-1.10/h in the temperature range of 45-48 degrees C. Activity of the extracellular neutral proteinase excreted by 1.3 mg/mL dry mass during 8 h of the postexponential and stationary growth phases decreased from its maximum value of 0.23 TU/mL at 40 degrees C to 0.13 and 0.06 TU/mL at 45 and 48 degrees C, respectively. Formation of the extracellular serine proteinase decreased even more - from 0.18 TU/mL at 40 degrees C to 0.06 and 0.03 TU/mL at 45 and 48 degrees C, respectively. Sporulation, expressed as the portion of sporangia with refractile spores at the 6th h of the stationary phase decreased from 46% at 40 degrees C to 17 and 3% at 45 and 48 degrees C, respectively. PMID- 8500778 TI - Antimicrobial activity determined in strains of Bacillus circulans cluster. AB - Wild-type strains of the genus Bacillus were screened for antimicrobial activity. Two strains exhibited antimicrobial activity against Micrococcus luteus and were identified as Bacillus polymyxa MIR-23 and Bacillus circulans MIR-13. Bacillus polymyxa MIR-23 was active against Escherichia coli, Pseudomonas aeruginosa and Aspergillus niger, whereas Bacillus circulans MIR-13 did not show activity against these microorganisms. Bacillus subtilis ATCC 6633 and B. polymyxa ATCC 10401 were used as standard antibiotic-producer strain and showed different antimicrobial profiles and yields from B. polymyxa MIR-23. The different antimicrobial profile of the two selected strains could possibly be used as a taxonomic marker. PMID- 8500779 TI - Antimicrobial effects of some dicarbonyl and tricarbonyl sugar hydrazone derivatives. AB - Several dicarbonyl and tricarbonyl sugars were prepared by the use of fungal enzymes and the antimicrobial effects of their N,N-diphenylhydrazine derivatives were tested. G+ bacteria were more sensitive than G- bacteria especially in the group of disubstituted compounds. Peracetyled derivatives were not active. No inhibition of yeast growth was found. PMID- 8500780 TI - Primary biodegradation of amine oxide and quaternary ammonium amphiphiles. AB - Biodegradation of two amphiphilic "soft" antimicrobially active derivatives of lauric (dodecanoic) acid, a quaternary ammonium salt and an amine oxide bearing an amide or ester group, was followed using microorganisms from activated sludge. Primary biodegradation was determined by ion-selective electrodes, total biodegradation as the chemical oxygen demand. Though organic ammonium salts quickly undergo primary biodegradation, the rest of the molecule is difficult to destroy. In contrast, amine oxides are easily biodegradable. PMID- 8500781 TI - Ultracytochemical localization of dihydroorotate dehydrogenase in mitochondria and vacuoles of Saccharomyces cerevisiae. AB - The coenzyme-independent dihydroorotate dehydrogenase (EC 1.3.3.1) linking the pyrimidine biosynthetic pathway to the respiratory chain, was ultracytochemically localized by the tetrazolium method in derepressed exponential-phase cultures of Saccharomyces cerevisiae. Biochemical analysis showed a considerable variation of this enzyme activity in inverse proportion to the aeration of the yeast cultures. The assay also showed that after prefixation of yeast cells with 1% glutaraldehyde at 0 degrees C for 20 min, approximately one-half of the enzyme activity was preserved. The cytochemical reaction mixture contained dihydroorotate (2 mmol/L), thiocarbamyl nitroblue tetrazolium (0.44 mmol/L), phenazine methosulfate (0.16 mmol/L) and KCN (1.7 mmol/L) in Tris-HCl buffer (100 mmol/L) of pH 8.0. The osmicated formazan deposits features envelopes of mitochondria and of nuclei and were prominent in the mitochondrial inclusions and in the vacuolar membranes. The latter sites of dihydroorotate dehydrogenase activity represent biosynthetic activity in yeast vacuoles, still generally assumed to function as yeast lysosomes and storage organelles. In the light of the generally observed invasions of juvenile yeast vacuoles into mitochondria, the enzymic sites observed in mitochondrial inclusion were considered as evidence of the interactions of yeast vacuoles and mitochondria. Transfer of vacuolar membranes with dihydroorotate dehydrogenase activity into mitochondrial matrix is suggested. PMID- 8500782 TI - Antimicrobial spectrum of bacteriocin-like substances produced by rumen staphylococci. AB - Five strains of rumen coagulase-negative adherent and ureolytic staphylococci were obtained as bacteria producing bacteriocin-like substances or lantibiotics. All examined staphylococci produced inhibitory agents which showed a wide range of inhibition against Gram-positive and Gram-negative indicator organisms from different sources. Clear zones of inhibition (diameter 1-6 mm) dominated. Most bacteriocin-like substances produced by the strains were stable and sensitive to trypsin, susceptible to chloroform vapours and heat-sensitive. PMID- 8500783 TI - Dopamine agonists in Parkinson's disease: a look at apomorphine. AB - Apomorphine is a D1 and D2 dopamine receptor agonist with anti-parkinsonian properties qualitatively similar to those seen with L-dopa. It was first used in the treatment of Parkinson's disease by Schwab in the 1950s but owing to its short duration of action, the need for parenteral administration, and adverse reactions including nausea, vomiting, postural hypotension and sedation, it was not widely prescribed. In the early 1970s, Cotzias confirmed its potent anti parkinsonian effects and that some of its secondary effects were diametrically opposite to those seen with L-dopa. The advent of peripheral dopamine receptor antagonist drugs, which counteract the unwanted effects of apomorphine, and the development of new drug delivery systems including insulin pens and ambulatory mini pumps have led to the resurrection of apomorphine for the treatment of Parkinson's disease. Over the last five years in Europe, the drug has proved to be a major advance in the treatment of refractory "on-off" oscillations in Parkinson's disease. It has also been used as a diagnostic test for dopaminergic responsiveness in Parkinson syndromes and tremors of uncertain aetiology. The drug has also proved particularly useful in dealing with certain "off-period" disabilities, including pain, bladder dysfunction, dystonia and gastro-intestinal symptoms. Continuous steady state infusion of apomorphine by mini-pump may reduce the severity of "on" phase dyskinesias over time. The drug has also proved useful in the clinical pharmacological investigation of the pathophysiology of the motor response to dopaminergic drugs in Parkinson's disease and the occurrence of involuntary movement sequences. Neuropsychiatric side-effects are relatively infrequent when compared with ergolene dopamine agonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500784 TI - Carbocisteine improves the mucociliary transport rate in rats with SO2-induced bronchitis. AB - In order to study the effect of carbocisteine on the mucociliary function of the respiratory tract, we performed a double-blind study on rats with SO2-induced (400 ppm) hypersecretion. During the experimental bronchitis, the treated group of rats received carbocisteine through a stomach tube at a dose level of 500 mg/kg for 15 days, whereas the untreated group of rats received distilled water. After killing the rats, and following lung excision, the respiratory mucus was scraped off and collected by using a glass capillary. The mucus degree of purulence was macroscopically estimated and the mucus transport rate was measured by using the frog palate technique. The mean mucus relative transport rate, measured on the frog palate, was 0.60 +/- 0.17 in the untreated group and was significantly higher (P < 0.01) in the treated group (0.73 +/- 0.14). Carbocisteine also significantly altered (P < 0.01) the mucus macroscopical aspect, leading to a decrease in the number of rats with purulent mucus. These results suggest that carbocisteine maintains an efficient mucus transport rate, leading to a less infected respiratory tract. PMID- 8500785 TI - Dose-response study of metoclopramide in gastroesophageal reflux in infancy. AB - Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H1 and H6, entered a double-blind placebo controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal (n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C1h. No side effects were observed. A similar study should be performed after repeated dosing regimen. PMID- 8500786 TI - Effect of famotidine on renal transplant patients treated with ciclosporine A. AB - The influence of a 7-day course of 40 mg famotidine administered orally on the pharmacokinetics of ciclosporine A at steady-state has been investigated in 10 renal transplant patients. Famotidine did not appear to significantly alter the pharmacokinetics of ciclosporine A. This might be ascribed to the limited potential of famotidine for inhibiting microsomal enzyme function. Moreover, plasma creatinine concentrations and creatinine clearance remained stable. Our results suggest that famotidine has no noticeable interaction with ciclosporine A. PMID- 8500787 TI - Molecular defect in human erythropoietic protoporphyria with fatal liver failure. AB - We investigated the molecular basis of ferrochelatase in a Japanese patient with erythropoietic protoporphyria (EPP), complicated by fatal liver failure, and defined a novel point mutation in the ferrochelatase gene. cDNAs were synthesized using Epstein-Barr-virus-transformed lymphoblastoid cells from the proband. cDNA clones encoding ferrochelatase in the proband were isolated by amplification using the polymerase chain reaction. There were two sizes of ferrochelatase cDNAs; one was normal in size, the other being smaller. Sequence analysis of the abnormally sized cDNA clones revealed that they lacked exon 9 of the ferrochelatase gene. Genomic DNA analysis demonstrated that the proband had the abnormal allele and that it contained a G to A point mutation at the first position of the donor site of intron 9. An identical mutation was detected in the affected family members of the proband by allele-specific oligonucleotide hybridization analysis. EPP is inherited in an autosomal dominant manner in this family. PMID- 8500788 TI - HLA-A/B haplotye frequencies among U.S. Hispanic and African-American populations. AB - HLA-A/B haplotype frequency tables were developed for U.S. Hispanic and African American populations from data collected from paternity cases. Two Hispanic tables were developed; one was based on data from Hispanics in the northeast U.S. and Florida and designated the Caribbean table whilte all other Hispanics were included in a table designated the Mexican table. The total number of individuals whose haplotypes were included in the Caribbean, Mexican, African-American tables was 1635, 2230, and 3134, respectively. Statistical comparisons were made of haplotype frequencies among these tables and tables previously reported. PMID- 8500789 TI - The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. AB - The maternal transmission of Leber hereditary optic neuropathy (LHON) can be explained by the mitochondrial DNA mutation. However, the characteristic mode of inheritance, i.e. male predominance and reduced penetrance with late onset in females, suggests the simultaneous involvement of an X-linked gene in development of optic atrophy. We have assessed such a two-locus model of mitochondrial and X linked genes in Japanese LHON pedigrees. The goodness-of-fit test on individual male sibship data with a presumed heterozygous mother from maternal lines showed an excellent fit for the 1:1 segregation of a putative X-linked gene, thus supporting the two-locus model in the Japanese pedigrees tested. A calculated frequency of the X-linked gene was 0.10. We could not determine whether the present value is different from the reported one (= 0.08). On the other hand, the estimated penetrance for a heterozygous female was 0.196 +/- 0.039, which was about twice as high as the reported value (= 0.111) with a 5% level of significance. Such a high penetrance may primarily arise from a low threshold of LHON manifestation, suggesting the ethnic difference between the LHON pedigrees in Japan and in other countries. PMID- 8500790 TI - FFU complex: an analysis of 491 cases. AB - A study of 491 patients with femur-fibula-ulna (FFU) complex is presented. The term FFU complex has been proposed for cases in which the femur, fibula and/or ulna show defects, which tend to be associated. These cases are usually sporadic. Some rare anomalies of the arms which are present are particularly frequent in FFU complex. These are amelia, peromelia of humerus, humero-radial synostosis and defect of ulna. In our study, 491 patients were investigated for involvement of limb malformations. Our results, showing nearly equal proportions of the most common malformations in four analysed groups (with one, two, three and four limbs affected) supports the hypothesis that even if one arm or one leg only is affected, the cases may still be classifiable as FFU complex. There is a striking asymmetry in presence and in degree. All malformations are more often unilateral than bilateral. Upper limbs are affected more often than lower limbs. The right side and the male sex are preferentially affected. The limb malformations present in the FFU complex are different from those seen in most other types of limb defects, so there is virtually no overlap between FFU and other limb malformations. Some arguments in favour of early somatic mutation as a cause are discussed. PMID- 8500791 TI - Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation. AB - The differential diagnosis of the genetic bleeding disorders, hemophilia A and von Willebrand disease, is occasionally confounded by the close molecular relationship of coagulation factor VIII and von Willebrand factor (vWF). This report describes the autosomal inheritance of a hemophilia A phenotype due to a mutation of vWF that results in defective factor VIII binding. The proband was a female patient with low levels of factor VIII activity. Polymerase chain reaction (PCR) amplification and DNA sequencing were employed to examine exons encoding the putative factor VIII binding domain of vWF. The patient was found to be homozygous for a single point mutation causing a Thr-->Met substitution at amino acid position 28 in the mature vWF subunit. The phenotypic expression of the mutation was determined to be recessive because heterozygous family members were clinically unaffected. Recombinant vWF containing the observed amino acid substitution was expressed in COS-1 cells. The mutant vWF was processed and secreted normally, and was functionally equivalent to wild-type vWF in its ability to bind to platelets. However, the mutant failed to bind factor VIII, demonstrating that the mutation was functionally related to the observed hemophilia phenotype. The family we describe demonstrates the recessive inheritance of a recently recognized class of genetic bleeding disorders, we call "autosomal hemophilia." We conclude that vWF mutation may be an under recognized cause of hemophilia, especially in cases where the inheritance pattern is not consistent with X-linked transmission. PMID- 8500792 TI - A parental combination analysis for ABO-HP interaction in a Bengali population. AB - Blood samples from 577 couples and their 657 offspring of Bengali caste group derivation were used to study interactions between ABO blood groups and haptoglobin (HP) systems. There was no significant sex difference in HP distribution among the parents. Significantly higher incidences of HP*1 allele were noted in the offspring of ABO-incompatible parental combinations in comparison with those in the offspring of ABO-compatible parents. PMID- 8500793 TI - Human zinc finger gene ZNF23 (Kox16) maps to a zinc finger gene cluster on chromosome 16q22, and ZNF32 (Kox30) to chromosome region 10q23-q24. AB - Two members of the KOX gene family, ZNF23 (KOX16) and ZNF32 (KOX30), have been mapped by in situ hybridization to chromosome regions 16q22 and 10q23-q24, respectively. The map location of ZNF23 and ZNF32 placed these zinc finger protein genes near to chromosome loci that, under certain in vitro conditions, are expressed as fragile sites (FRA16B, FRA16C) and (FRA10D, FRA10A, FRA10B and FRA10E). Human zinc finger gene ZNF32 maps to a chromosome region on 10q23-24 in which deletions have been observed associated with malignant lymphoma on 10q22-23 and with carcinoma of the prostate on 10q24. ZNF23 is located on 16q22 in a chromosomal region that has been involved in chromosome alterations characteristic of acute myeloid leukemia. A second Kox zinc finger gene (ZNF19/KOX12) was recently mapped to the same chromosome region on human chromosome 16q22. In the analogous murine position, the murine zinc finger genes Zfp-1 and Zfp-4 are found in the syntenic 16q region of mouse chromosome 8. Thus, ZNF19 and ZNF23 might be members of an evolutionarily conserved zinc finger gene cluster located on human chromosome 16q22. PMID- 8500794 TI - Molecular cytogenetic characterization of three familial cases of satellited Y chromosomes. AB - Three families in which a satellited Y chromosome (Yqs) was segregating without apparent phenotypic effect were re-investigated with non-isotopic in situ hybridization methods. Active nucleolus organizer regions were seen in the distal long arm region of all Yqs chromosomes studied and in situ hybridization with the probe D15Z1 showed that, in all three families, the Yqs was the result of a 15p;Yq translocation. In one case, an additional focus of D15Z1 hybridization was seen on 21p. PMID- 8500795 TI - Charcot-Marie-tooth disease 1A (CMT1A) associated with a maternal duplication of chromosome 17p11.2-->12. AB - We report here the second case of Charcot-Marie-Tooth disease 1A (CMT1A) with a cytogenetically visible de novo direct duplication of 17p11.1-->17p12. A male child who was initially referred for developmental delay and dysmorphism was subsequently shown to have significantly reduced motor nerve conduction velocities characteristic of CMT1A. This patient was not informative for the DNA markers mapping to the CMT1A region; however, with DNA markers pA10-41 and EW503 that map proximally and distally with respect to the disease locus, a dosage difference was observed between the two alleles. Comparison with parental genotypes indicated a de novo maternal duplication. Pulsed field gel analysis using probe VAW409R3a indicated that a 500-kb SacII junction fragment usually associated with CMT1A was absent in this patient. These findings confirm that the disease phenotype is probably caused by a gene dosage effect. PMID- 8500796 TI - Duplication of the short arm of the X chromosome in mother and daughter. AB - An 11-year-old girl with short stature, mental retardation, and mild dysmorphic features was found to have an inverted duplication of most of the short arm of the X chromosome [dic inv dup(X)(qter-->p22.3::p22.3-->cen:)]. Her mother, who is also short and retarded, carries the same duplication. Fluorescence in situ hybridization with an X chromosome library, and with X centromere-specific alpha satellite and telomere probes, was useful in characterizing the duplication. In most females with structurally abnormal X chromosomes, the abnormal chromosome is inactivated. Although the duplicated X was consistently late replicating in the mother, X chromosome inactivation studies in the proband indicated that in 11% of her lymphocytes the duplicated X was active. PMID- 8500797 TI - Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. AB - We have investigated the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene and identified two new alleles of the system. We have shown that the polymorphism is caused by the variable copy number of an 86-bp sequence, by using the polymerase chain reaction and primers immediately flanking the repeat region, and by direct sequencing. The repeat region contains three potential protein-binding sites and therefore the variable copy number may have functional significance. PMID- 8500798 TI - A 40-nucleotide repeat polymorphism in the human dopamine transporter gene. AB - A new polymorphic 40-nucleotide repeat in the human dopamine transporter gene is described. It may underlie individual differences in susceptibility to several neuropsychiatric diseases. PMID- 8500799 TI - A beta-galactosidase gene mutation identified in both Morquio B disease and infantile GM1 gangliosidosis. PMID- 8500800 TI - Actinomycosis mimicking carcinoma of the maxillary sinus. AB - Human actinomycosis may pose a diagnostic problem at times and is often mistaken for a neoplasm. A thirty-five year old male was clinically diagnosed as a case of carcinoma of the right maxillary sinus on the basis of history, clinical presentation and radiologic findings. Tissue biopsy was negative for malignancy on three consecutive occasions. Microscopic examination showed bits of granulation tissue and fragments of filamentous structures. On microbiological examination, Actinomyces israelii was isolated and fungus culture was negative. Long term Penicillin treatment caused disappearance of all signs and symptoms. The report highlights the importance of bearing in mind the fact that certain rare, chronic, suppurative granulomatous infections, like actinomycosis, may mimic malignancy. PMID- 8500801 TI - One stage reconstruction of extensive abdominal wall defect with bilateral tensor fascia lata (TFL) flaps. AB - An extensive anterior abdominal wall defect, measuring 20cm x 20cm following a wide excision for recurrent abdominal wall tumor, was reconstructed with extended bilateral TFL flaps. Minimal sequelae have been observed in three year follow-up. Inspite of both sides TFL used for the reconstruction, patient has no difficulty in walking and day-to-day activities. PMID- 8500802 TI - Endobronchial leiomyoma. AB - Two rare cases of endobronchial leiomyoma are presented. Both cases presented with suppuration and destruction of ipsilateral lung. The diagnosis was confirmed by biopsy and pneumonectomy performed. The world literature of previously reported twenty two cases is reviewed and salient features elaborated. The tendency to treat such cases with antitubercular drugs in a country were tuberculosis is endemic should be deplored. PMID- 8500803 TI - Mucosal melanomas of the upper aerodigestive tract. AB - Mucosal melanoma of the upper aerodigestive tract is a rare disease with a relentless inexorable course. This lesion involved the nasal cavity, maxillary sinus and palate in two cases each all of whom underwent a radical excision. The disease did not respond to radiotherapy in two patients with nasopharyngeal involvement. One other patient died of distant metastasis within five weeks of diagnosis. Despite surgery offering variable disease free periods, the prognosis remains guarded. PMID- 8500804 TI - Fine needle aspiration cytology in the diagnosis of mass lesions of the salivary gland. AB - Fine needle aspiration was performed on 101 patients with mass lesions of the salivary gland. In 98 patients satisfactory material was obtained. This could be correlated with the histology done in 54 cases. There were 12 inflammatory lesions; 52 benign and 34 malignant tumors. Of the malignant tumors 32 were primary salivary tumors and one case each of lymphoma and leukemia. The overall accuracy was 97 per cent. There were no false positives but one false negative diagnosis. In two cases there was a discrepancy of tumor type between the cytology and histopathology; these were due mainly to sampling errors. This study documents that cytomorphology can characterise a wide range of histologically described lesions including the rare epithelial myoepithelial tumor. The application of stringent criteria in the diagnoses of salivary lesions, even inflammatory conditions like chronic sialadenitis, avoids over-diagnosis. Both inflammatory and neoplastic lesions may be cystic. These cystic lesions may prove to be a pitfall in cytology. Reaspiration of cystic lesions especially from residual solid areas greatly improves accuracy. We suggest that a fore-knowledge of tumor type preoperatively greatly reduces surgery in clinically questionable salivary lesions. PMID- 8500805 TI - Neutropenic enterocolitis and cecal perforation in acute lymphatic leukemia. AB - A ten year old boy who died of the consequences of an infrequent gastrointestinal complication, whilst on induction chemotherapy for acute lymphatic leukemia, is being reported. Recent trends in the diagnosis and management of typhilitis or neutropenic enterocolitis have been reviewed. PMID- 8500806 TI - Gastric teratoma in infants--a report of two cases. AB - Gastric teratoma is an exceeding rare lesion seen most often in male infants. Two cases of gastric teratoma, the first in a three and half month male, and the second in a one year old male child are reported. In the first case, the tumour was more solid, while in the second case it was a solid-cystic mass. These two cases represent the additions to the few, limited, known gastric teratomas reported in the world literature. PMID- 8500807 TI - Sarcoma-like nodule in ovarian mucinous tumour (a case report). AB - Sarcoma-like mural nodule, a morphologically benign epulis-like tumour with osteoid formation in the wall of mucinous tumour of borderline malignancy is described. The pattern simulated those of malignant giant cell tumour of soft part and was considered to be a reactive process that has no effect on the prognosis of the patient. This case, second to be reported from India and is in addition to the other thirteen cases reviewed. The case under report had in addition osteoid-formation which have not been reported in the literature. PMID- 8500808 TI - Carcinoma of lung with special reference to adenocarcinoma (an autopsy study of 122 cases). AB - We report morphological observations on 122 autopsied cases of lung carcinoma during the years 1974-1989, with emphasis on 44 cases of adenocarcinoma. Adenocarcinoma was the commonest histological type encountered (36%), confirming the trend reported in Western countries. It was also noted that nearly 50% of cases of adenocarcinoma were in the central zone, which is contrary to reported literature. 92% of small cell carcinoma, 87% of epidermoid carcinoma, 64% of combined carcinomas and 48% of adenocarcinomas were centrally located, while 91% of bronchioloalveolar carcinomas and 88% of large cell carcinoma were located peripherally. Of the 44 cases of adenocarcinoma, 23 were peripheral and 21 were central. In ten out of the 21 cases of central adenocarcinoma the tumour was confined to the bronchial tree without any parenchymal involvement. This type of gross morphology has not been described in adenocarcinoma so far. In the other 11 cases, there was a tumour in the lung parenchyma involving the bronchus. In these cases, it was not possible to decide whether bronchial involvement was primary or secondary, but bronchial obstruction due to a polypoid mass was present in three of these cases. PMID- 8500809 TI - Bone scans in neuroblastoma. AB - Eighty-Six patients of neuroblastoma ranging in age from four months to 15 years were studied with 99m Tc-MDP for total skeletal survey over a period of seven years (1983-1990). The diagnosis of neuroblastoma was based on bone marrow examination, FNAC, lymph node biopsy, histopathology. Bone imaging was performed three hrs. after intravenous administration of 99m Tc-MDP. Out of 86 patients, 45 patients had positive bone scan showing osseous concentration in 122 sites and extraosseous concentration in 34 sites. Seven patients had liver metastases. None of these liver metastases showed concentration of MDP. Fourteen patients underwent surgery for the primary tumour at the time of bone scanning. Ten patients were studied at the time of follow up, of which four patients showed good response as bony metastases were not demonstrated on bone scintigraphy and X rays. In conclusion, bone scan is an useful test in neuroblastoma in delineating the bony metastases and also in assessing the efficacy of chemotherapy in these patients. PMID- 8500810 TI - Diagnostic use of filarial antibody and antigen isolated from hydrocele fluid for human filariasis. AB - Paired samples of serum and hydrocele fluid of filarial patients associated with hydrocele were analysed for filarial antibody and antigen. Sera samples showed higher titers of filarial antibody and antigen compared to their corresponding hydrocele fluid samples. HFIgG isolated from hydrocele fluid was equally useful as FSIgG isolated from serum and detected filarial antigen in 23 out of 26 microfilaraemic sera, 7 out of 10 chronic sera and 3 out of 18 endemic normal sera by inhibition ELISA. Filarial antigen was isolated from hydrocele fluid. In inhibition ELISA antigen fraction, HFA-9 (20-25 kDa) isolated by sodium-dodecyl sulphate-polyacrylamide gel electrophoresis showed high reciprocal antigen titer of 2048. This active antigen fraction was evaluated for its diagnostic utility in comparison with Wuchereria bancrofti microfilariae excretory-secretory antigen (Wb mf ES Ag) in inhibition ELISA. Both antigen preparations detected filarial antigen in about 80% of microfilaraemic sera, 60% chronic sera and 20-30% of endemic normal sera. This study showed that antibody and antigen isolated from hydrocele fluid were equally sensitive as FSIgG and Wb mf ES Ag in the detection of filarial antigen by inhibition ELISA. Thus hydrocele fluid may be used as an alternative source for the isolation of antibody and antigen of immunodiagnostic importance. PMID- 8500811 TI - Biochemical and morphological changes of spermatozoa in progestin-androgen injected rats. AB - Bimonthly injections (im) of medroxyprogesterone acetate (MPA, 5 mg/0.2 ml) and testosterone enanthate (TE, 2.5 mg/0.2 ml) to rats for 30 and 60 days induced oligospermia. The sperms from epididymis had defective metabolism, alterations in their morphology, viability and acrosome integrity. Thus this altered sperm function resulted in reduction in the fertility rate of MPA+TE treated animals. PMID- 8500812 TI - Correlation of phospholipid loss in goat whole blood with solvochromic properties of antiamebics like emetine, metronidazole and diloxanide furoate. AB - Phospholipid content of whole blood lipid decreases significantly when goat blood is incubated for different length of time with different amebicidal agents (e.g., emetine, metronidazole and diloxanide furoate). The plots of relative per cent phosphate loss against incubation period show biphasic nature and suggest that the rates of phospholipid loss bears some relation with the drug's lipophilicity (log P in 1 octanol/water system). The absolute phospholipid loss seems to be governed by the drug's aquasolubility. Implication of these finding were discussed in terms of their clinical profiles assuming that the loss of phospholipid is due to drug's binding with the phospholipid layer in amebic cyst coat, being the first step which may trigger a chain of events leading to the onset of drug action. PMID- 8500813 TI - Antidiabetic effects of a glycoside of leucopelargonidin isolated from Ficus bengalensis Linn. AB - Glycoside of leucopelargonidin isolated from the bark of F. bengalensis demonstrated significant hypoglycemic, hypolipidemic and serum insulin raising effects in moderately diabetic rats with close similarities to the effects of a minimal dose of glibenclamide. The main difference observed in their effects was that the former significantly enhanced the fecal excretion of sterols and bile acids while the later has no such action even though both controlled hypercholesteremia. PMID- 8500814 TI - Aluminum ingestion alters behaviour and some neurochemicals in rats. AB - Effect of aluminum (Al) has been investigated on the brain of rats exposed to this metal (500 mg Al/liter in drinking water) daily for 180 days. A significant reduction in the spontaneous locomotor activity was noticed after 90 and 180 days of Al exposure to the rats, the magnitude of the change being almost identical at both the time intervals. Aluminum exposure also produced significant deficits in acquisition and retention of learned response in active avoidance situation, these changes being time dependent. A significant retardation of the extinction of the learned task was noted in Al exposed rats especially at 180 days. There was significant increase in the lipid peroxidation and decrease in the activity of Mg(2+)-ATPase and Na+,K(+)-ATPase in the brain of rats at 180 days after Al exposure. The increase in the contents of the metal was maximum in rest of the brain region (87% of control) followed by hippocampus and cerebral cortex (59% of controls), cerebellum and corpus striatum (43% and 44% of controls, respectively) after 180 days. Whether Al is responsible to initiate neurotoxic effects by producing changes in the structure and function of the plasma membrane needs further investigations. PMID- 8500815 TI - A hemolytic protein from cultured mycelia of mushroom, Termitomyces clypeatus. AB - A hemolytic protein was purified from cultured mycelia of T. clypeatus. Some of the physico-chemical properties of the hemolysin were studied. The protein was analysed to be a lipoprotein and delipidation removed its hemolytic property. The monomeric protein subunit of the lipoprotein had a molecular weight of 64,000. Mode of action of the hemolysin were studied by observing protections of sugar and lipid components to hemolysin mediated lysis of red blood cells. It was observed that the hemolysin possibly interacted with the phospholipid components of the blood cells causing lysis. PMID- 8500816 TI - Biochemical studies on stimulation of mouse peritoneal macrophages by interaction with preformed immune complexes. AB - Mouse peritoneal macrophages (MPM) were observed to be stimulated by both in vivo and in vitro interactions with preformed HSA-anti HSA immune complexes (IC) having different antigen-antibody ratios. This was indicated by cellular alterations in morphology, increase in cellular protein and lysosomal enzyme contents and a marked fall in 5' nucleotidase level. Analysis of cellular proteins of IC-elicited cells by SDS-polyacrylamide gel electrophoresis showed accumulation of 80, 47, 33, 28, 18 and 14 kDa proteins. Insoluble immune complexes at equivalence (IC-Eq) was found to be more effective in the stimulation process as compared to the soluble antigen excess complexes (IC-Ag). These IC-elicited cells secreted lesser amounts of lysosomal hydrolases when explanted in culture medium as compared to resting cells, whereas in vitro stimulation of resident MPM with IC resulted in enhanced lysosomal hydrolase release. IC-induced lysosomal secretion was time and dose dependent and varied with the nature of the complexes. Complement coated immune complexes (IC-CC) induced maximum enzyme secretion followed by IC-Eq and IC-Ag. PMID- 8500817 TI - Hydrolytic enzymes of rhesus placenta during Plasmodium cynomolgi infection: ultrastructural and biochemical studies. AB - Placenta in monkey demonstrated altered pathophysiology after P cynomolgi infection. The electronmicroscopic observations showed slight complete focal necrosis of the placental tissue, besides alterations in total protein, phosphatases and proteinases. These changes in cellular constituents of placenta during malaria infection may be responsible for malfunctioning of the organ and in turn, abnormal development of foetus. PMID- 8500818 TI - Interaction of exercise and age on substrates of carbohydrate metabolism. AB - Changes in blood lactate, pyruvate, glucose and tissue glycogen were used as indices to evaluate the extent of effects of physical conditioning in young and old male rats. Rats were trained on a running wheel and swimming tank for 10 weeks. Biochemical estimations of lactic acid (LA) pyruvic acid (PA) and glucose (GL) in plasma and glycogen in cardiac and slow-twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) skeletal muscles of trained animals were conducted and compared with those of sedentary control rats. Blood parameters showed a decrease upon training in both young and old rats, though of variable significances, between exercise types. Glycogen levels in the cardiac and skeletal muscles increased in all groups with the exception in SOL of older trained animals. Hepatic glycogen exhibited an insignificant increase in all groups. Results suggest that, though the trends of responses of both young and old rats to exercise follow a comparable path, the magnitudes of changes are definitely impressed upon appreciably by increasing age. PMID- 8500819 TI - Impact of electropolarity treatment on contractile kinetics of gastrocnemius muscle of toad (Bufo melanostictus) during denervation. AB - The twitch properties of denervated muscle were found to be altered contributing to the derangement in the contractile machinery of the denervated muscle. Cathodal polarity treatment minimized the fluctuations and tried to restore denervated muscle back to normalcy to some extent. The anodal polarity treatment was not able to produce favourable effect. The differential effect of polarity treatment on the contractile kinetics of the denervated muscle is discussed. PMID- 8500820 TI - In vivo effect of cyanate on serum and eye lens in rat. AB - Supplementation of cyanate in rats caused a significant decrease in serum GSH and increase in calcium and phosphate level both in serum and lens. Consequently, these changes led to induce acidosis uremia in serum and hypercalcemia and hyperphosphatemia in lens which may be possible causing factor for cataract. PMID- 8500821 TI - Insecticidal activity of Ranunculus sceleratus (L.) against Drosophila melanogaster and Tribolium castaneum. PMID- 8500822 TI - Effect of dietary methionine and inorganic sulfate with and without calcium supplementation, on urinary calcium excretion of guinea pigs (Cavia porcellus). AB - Supplementation of sodium sulfate and DL-methionine along with the standard diet to guinea pigs nearly doubled the urinary calcium in 6 weeks. This was probably due to decreased tubular reabsorption of calcium which was complexed with sulfate in the tubular lumen. A mild calcium load didn't further enhance calcium excretion in sodium sulfate supplemented group, but did so in methionine supplemented group. It may be due to methionine which might have increased the intestinal absorption of calcium. Both of these compounds increased citric acid excretion and decreased magnesium excretion. PMID- 8500823 TI - Embryonic/fetal mortality after exposure to tritiated water in pregnant Swiss albino mice during different gestation periods. AB - Pregnant Swiss albino mice were given a priming injection(im) of tritiated water (HTO) at the dose rate of 2.3 and 5 microCi/ml body water (74, 111 or 185 KBq/ml body water) at 0, 6 and 14 day post conception (d.p.c.) and were subsequently maintained on tritiated drinking water ad libitum during preimplantation (0-5 d.p.c.), organogenetic (6-12 d.p.c.) or fetal (14-18 d.p.c.) period, respectively. On day 18 of gestation the females were sacrificed by cervical dislocation to record the implant sites per dam and embryonic/fetal mortality. Significant reduction was observed in average implant sites per dam when the females were exposed to any of the three doses during the preimplantation period due to embryonic resorption before implantation. However, the same was found to be within the normal range when mothers were exposed during the organogenetic or fetal period. Prenatal mortality (embryonic resorption/fetal death) was higher after in utero exposure to different doses during preimplantation period as compared to organogenetic period, but mortality did not occur after exposure to any of the doses during the fetal period. Occurrence of mortality was found to be dose dependent. PMID- 8500824 TI - Reduction of UV-induced mitotic delay by caffeine in BUdR-substituted plasmodia of Physarum polycephalum. AB - Chromosomal DNA of the synchronously mitotic plasmodia of P. polycephalum was substituted with 5-bromo-2'-deoxyuridine, by growing the plasmodia during S phase, on a medium containing this nucleoside analog. A strong synergism was observed between bromodeoxyuridine and UV-irradiation, in late G2-irradiated plasmodia in that, the mitotic delay obtained in them was much more than a simple sum of the delays induced by these two agents individually. It was also observed that the mitotic delay in this system is reduced significantly by different concentrations of caffeine applied immediately after irradiation and there was a stage specificity in this effect. The reduction in mitotic delay was maximum (80%) in those plasmodia irradiated 20-30 min before control metaphase, when mitogenic factors also reach their maximum activity in this system. It is proposed that the mitotic delay reducing effect of caffeine is due to its ability to promote the activity of the mitogenic factors, largely independent of the system which is responsible for monitoring the state of the chromosomal DNA. PMID- 8500825 TI - Changes in catalase activity during follicular growth, atresia and luteinization in rat ovary. AB - Quantitative changes have been observed in the catalase activity during follicular growth, induced atresia and in corpora lutea of cycle and pregnancy. Large growing and preovulatory follicles showed higher enzyme activity as compared to the smaller follicles; the activity was mainly present in the thecal layer of the preovulatory follicle. After the blockade of ovulation with barbiturate, the activity increases significantly in the whole follicle and also in the thecal layers till third day of ovulation and afterward it declines on 5th day, suggesting that rise in catalase activity may exert a protective function against lytic actions of peroxide which is known to be produced in the ovary during several metabolic and steroidogenic events. The corpora lutea of the cycle showed significantly less enzyme activity than the corpora lutea of pregnancy. The significance of catalase activity during follicular and corpus luteum degeneration is discussed. PMID- 8500826 TI - Thyrotropin releasing hormone-induced potentiation of spinal monosynaptic reflex in rats in vitro. AB - Superfusion of thyrotropin-releasing hormone (TRH) in neonatal rat spinal cord in vitro produced dose (0.01-1.00 microM) dependent potentiation of monosynaptic reflex (MSR) which was maximum (44% of control) at 1 microM of TRH. But no ventral root depolarization was observed with TRH (1 microM) although potassium concentration out side ([K+]0) when increased produced a depolarization at the magnitude of 0.2 mV/mM of [K+]0. TRH-induced potentiation of MSR was not altered in spinal cords, obtained from the animals pretreated with 5,7 dihydroxytryptamine or 6-hydroxydopamine. Neither serotonin antagonists (spiperone, ketanserin, cyproheptadine or 3-troponyl-indole-3-carboxylate) nor adrenergic antagonists (phentolamine or haloperidol) could attenuate TRH-induced potentiation. Inhibition of MSR observed in the spinal cord elicited by stimulating the adjacent dorsal root was unaffected by TRH. The results suggest that, TRH potentiates MSR by directly acting on the motoneurons, without involving presynaptic serotonergic or catecholaminergic neuronal systems or the disinhibition of pre- or post-synaptic inhibition in the spinal cord. PMID- 8500827 TI - Effect of verapamil post-treatment in myocardial reperfusion injury. AB - Effect of verapamil post-treatment (0.2 mg/kg bolus, followed by 0.01 mg/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (20 min) followed by 1 hr of reperfusion was studied in open chest pentobarbitone anaesthetized dogs. In control dogs 1 hr of reperfusion failed to cause any improvement of depressed myocardial contractility (LVdP/dtmax and LVEDP) caused by 20 min of ischemia, which confirmed the earlier reported phenomenon of 'Stunned Myocardium'. Myocardial ischemia caused a significant loss of high-energy phosphate (HEP) content of the affected myocardium (ATP decreased by 60% and CP decreased by 75% of non-ischemic level). Following 1 hr of reperfusion, myocardial ATP was not replenished, though creatine phosphate became near normal. When verapamil was administered just before reperfusion, it showed a profound beneficial effect on the incidence of fatal reperfusion arrhythmias. At the end of 1 hr of reperfusion in this group, the recovery of the myocardial contractility was incomplete, but a significant replenishment of the myocardial HEP content was observed. Thus verapamil post-treatment can prevent reperfusion induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depressant effect. PMID- 8500828 TI - Induction of prophage lambda by nitrofurantoin and its modulation by butylated hydroxytoluene, sodium arsenite and alpha tocopherol. AB - Nitrofurantoin induced prophage-lambda in E. coli K12 strain GY5027(lambda) in a dose dependent manner, the maximum induction being 10-fold the spontaneous induction level and the maximum efficiency of induction 74%. The lever extract used as a metabolizing mixture enhanced the induction level significantly. Chloramphenicol at a concentration of 20 micrograms/ml inhibited the prophage induction by nitrofurantoin, indicating that the induction required concomitant protein synthesis. Butylated hydroxytoluene(BHT) and sodium arsenite enhanced the nitrofurantoin induced prophage-lambda induction in E. coli GY 5027(lambda) cells in a dose dependent manner. The maximum modulations in induction level (I/Io) were achieved with 100 micrograms/ml BHT and 250 micrograms/ml sodium arsenite corresponding to a nitrofurantoin concentration of 15 micrograms/ml and were found significant on statistical analysis. alpha-tocopherol, however, did not produce any effect on the prophage-lambda induction by nitrofurantoin. PMID- 8500829 TI - 5'-Nucleotidase activity in retinol deficiency induced albino rats. AB - Retinol deficient rat liver, kidney and spleen showed a significant decrease in their enzyme activity (36% to 50%) compared to controls. The lectins could stimulate the enzyme activity in retinol deficient group by 57.6 to 92%, compared to controls (13.3% to 74%). Detergents increased the enzyme activity in retinol deficient tissue microsomes by 4.5%-80% in comparison to controls (10.3% to 119%). The results reveal alterations in membrane structure induced by retinol deficiency. PMID- 8500830 TI - Biotin deficiency causes alterations in glycosaminoglycans and glycoproteins in rat aorta. AB - Biotin deficiency produced by feeding raw egg white caused decrease in the concentration of many glycosaminoglycans (GAG) in the aorta in rats fed standard laboratory diet and atherogenic diet. This decrease has been observed to be due to the increased activity of enzymes involved in the degradation of GAG and glycohydrolases which cleave the carbohydrate components of glycoproteins. PMID- 8500831 TI - Mechanism of blood sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia chirayita. AB - Mechanism of blood sugar lowering by the crude/impure swerchirin (SWI) isolated from the hexane fraction of Swertia chirayita was investigated. Single oral administration of SWI (50 mg/kg, body wt) to fed CF rats induced about 60% (max.) fall in blood glucose by 7 hr post-treatment. This was associated with marked depletion of aldehyde-fuchsin stained beta-granules and immunostained insulin in the pancreatic islets. In vitro, glucose uptake and glycogen synthesis by muscle (diaphragm) was significantly enhanced by the serum of SWI-treated rat. At 100, 10 and 1 microM final concentration, SWI greatly enhanced glucose (16.7 mM) stimulated insulin release from isolated islets. It is therefore concluded that SWI lowers blood glucose level by stimulating insulin release from islets of Langerhans. PMID- 8500832 TI - Susceptibility of different rat tissues to non-enzymatic protein glycosylation in experimental diabetes. AB - Hyperglycemia was induced in Sprague-Dawley rats by alloxan and maintained for 2, 6 and 10 weeks without insulin treatment. Levels of glycosylated plasma proteins, hemoglobin and glycosylated tissue proteins of aorta, heart, kidney, liver and brain were estimated at these intervals. Protein glycosylation was observed to increase linearly as a function of period of hyperglycemia in all the tissues studied, except brain, in the following order: aorta > heart > kidney > liver. Protein glycosylation, leading to formation of covalently modified advanced glycosylated products and protein-protein adducts, may reflect disposition of these tissues to diabetic complications. PMID- 8500833 TI - Effect of new diamidines against Leishmania donovani infection. AB - The impact of interamidine distance on antileishmanial activity of new aryldiamidines have been evaluated against amastigotes of L. donovani in hamster. Of the 20 compounds tested, only four (2,8-diamidino-9,10-dihydrodibenzoxepin; 2,7-diamidinoxanthone; 2,7-diamidinothioxanthone and 2,7-diamidinoxanthene) showed significant inhibition (more than 80%) of multiplication of amastigotes in spleen. The interamidine distance in the structure appears to have bearing on antileishmanial activity. The observations made are likely to evoke new understanding on the structure activity relationship of diarylamidines. PMID- 8500834 TI - Chromosomal break points in irradiated and ethyl methane sulphonate treated leucocytes of patients with Down syndrome. AB - Frequencies of chromosomal damage in the peripheral leucocytes of patients with Down syndrome, on exposure to gamma rays (2Gy) or ethyl methane sulphonate (EMS, 1x 10(-4) M), were assessed. Analysis of break points in the chromosomes of irradiated cells revealed a non-random occurrence. Six of the break points observed in EMS-treated cells were found to overlap with those recorded in irradiated cells. Thirteen break points observed were found to correlate with the location of cancer-specific break points and four of these coincided with the bands where oncogenes have been located. Two break points were localised to the same bands as that of known heritable fragile sites. PMID- 8500835 TI - Induction and characterization of premature chromosome condensation in Drosophila synkaryons and implications to dosage compensation. AB - Premature chromosome condensation (PCC) was induced in Drosophila melanogaster cell hybrids, with Drosophila mitotic cells and interphase cells at different phases (G1,G1-S,S,S-G2 of the cell cycle, and from male and female, using standard cell fusion technique with polyethylene glycol (PEG). A combination of Feulgen and autoradiography was used to enhance the resolution of the PCC plates. It was possible to identify the characteristics of PCC's at G1, S and G2, and the transitory intermediate phases, which are comparable with respect to the characteristics of PCC's previously described for other species. Using the combined Feulgen-autoradiography technique it was possible to critically resolve the different phases including the transitory intermediate phases in greater detail. Analysis and comparison of results obtained from M (female) x S (female/male) and M (female) x G2 (female/male) hybrids have revealed that the X chromosome from the male could be identified as a distinct acrocentric entity which showed clear allocyclic, heteropycnotic characteristics. The results thus lead us to suggest that the X chromosome in such synkaryons is indeed early replicating as is the X chromosome of male larval salivary gland of Drosophila. The X chromosome morphology is also distinctly at an advanced stage of the cell cycle. On the basis of these findings it is concluded that X chromosome is hyperactive in the normally dividing diploid cells. PMID- 8500836 TI - Lack of correlation between mating activity and EST-1 polymorphism in three natural and laboratory populations of Drosophila bipectinata. AB - Est-1 polymorphism and mating activity have been studied in three natural populations of D. bipectinata and after 10 generations of their maintenance in the laboratory. The results indicate that the enzyme Est-1 variation was not significant within natural populations within F10 generation and also between different natural populations and F10 generation indicating the role of balancing selection in the maintenance of enzyme polymorphism in both natural and laboratory conditions. On the other hand, there was variability in the mating activity within natural populations and within F10 generation and also between natural population and F10 generation. However, there was no correlation between Est-1 polymorphism and mating activity. PMID- 8500837 TI - Epidermal water permeation in vertebrates: an in vitro study using tritiated water. AB - Structural lipids play an important role in the water holding property of the skin. beta emitters are known to pass through the skin barrier. A permeability cell was constructed and tritiated water was used to determine the rate of in vitro water permeation through the epidermis. The epidermal sheets from different classes of vertebrates were compared for water permeation. Some of the samples were treated with solvents, surfactants and conditioners, to fathom permeability changes of the epidermis after these treatments, at various time intervals. Solvent treated epidermal sheets show very high degree of permeation, both in rat pup skin and pigeon skin. Glycerol, Brij 99 and beewax treated skin shows negligible permeation; or rather, helps in retention of water compared to normal and solvent treated skin. Comparison of water permeation in rat, pigeon and lizard skin shows that the reptilian integument is more efficient, as it allows very less permeation of water compared to the avian and mammalian epidermis. These observations suggest that tritiated water could be used for determining in vitro water permeation through the epidermis. PMID- 8500838 TI - Modification of radiation damage in transformed mammalian cells by 5-bromo-2 deoxy-uridine and 2-deoxy-D-glucose. AB - The effects of 2-deoxy-D-glucose (2-DG) and 5-bromo-2-deoxy-uridine (BrdU) on gamma ray (60Co) induced damage were studied in monolayer cultures of transformed mammalian (BHK-21) cells. Micronuclei formation and changes in DNA content dispersion were used as indices of cytogenetic damage. Exposure of cells to BrdU (0.8 microM) for nearly two cell cycles before irradiation significantly increased micronuclei formation in exponentially growing cells. Incubation of irradiated cells under suboptimal growth conditions (in HBSS) for 4 hr, instead of growth medium, decreased the manifestation of damage. However, post irradiation presence of 2-DG (5 mM, equimolar with glucose; 4 hr) in growth medium or HBSS significantly increased radiation damage. The effects of 2-DG treatment following irradiation in plateau phase were quantitatively less. These results suggest that: (i) radiation induced DNA lesions leading to micronuclei formation in BrdU incorporated cells are partly repairable; (ii) 2-DG could increase radiation induced cytogenetic damage in transformed mammalian cells, possibly by inhibiting the cellular repair processes; and (iii) combination of 2 DG treatment may decrease the BrdU doses required for radiosensitization of proliferating tumour cell populations. PMID- 8500839 TI - Effectiveness of a unani therapy (sangesarmahi) in management of urinary stone disease. AB - A Unani medicine called fish stones, an isolate from the skull of Channa sp. when given to stone bearing patient daily in 3 equally divided doses (25 mg/capsule) for 5 days, spontaneously voided the stone in 36% of the stone patients during 5 days of therapy. The therapy did not influence the urinary chemistry and was not a powerful expulsion agent of stone but did effect on ureteric muscles to facilitate the movement of stone down the urinary tract. In guinea pigs, the therapy could not reduce the intensity of experimentally induced hyperoxaluria but showed several other beneficial effects. It decreased urinary uric acid and mucoprotein levels, serum LDH and ALT level; prevented rise in liver LDH and GAO activities and kidney-LDH activity. Histological examination revealed decreased intensity of calcification in liver, kidney and bladder tissues. PMID- 8500840 TI - Effect of hepatoprotective ayurvedic drugs on lipolytic activities during CCl4 induced acute hepatic injury in albino rats. AB - Daily treatment of CCl4(3 ml/kg body wt) for 7 days induced acute hepatic necrosis in albino rats. Treatment of CCl4 caused significant alterations in the activities of acid lipase, alkaline lipase, lipoprotein lipase of liver, kidney and adipose tissue and hormone sensitive lipase of adipose tissue of albino rat. Administration of hepatoprotective ayurvedic drugs (kumari asav, kumari kalp, arogyavardhini and tamra bhasma) concomitant with CCl4 counteracted the action of CCl4 on lipolytic enzymes exhibiting hepatoprotection. The possible physiological significance of alterations in lipolytic enzymes during hepatic necrosis induced by CCl4 and hepatoprotection by the above ayurvedic drugs is discussed. PMID- 8500841 TI - Additive effect of alcohol and nicotine on lipid metabolism in rats. AB - Administration of alcohol along with nicotine in rats showed an increase in the concentration of cholesterol, triglycerides, phospholipids and free fatty acids in serum and various tissues compared to that of alcohol fed rats. The increased cholesterogenesis was evidenced by the increased activity of HMG CoA reductase, increased incorporation of labelled acetate in to cholesterol and decreased hepatic degradation of cholesterol to bile acids. The concentration of cholesterol in HDL lipoprotein fraction decreased, while in LDL + VLDL fraction increased. Administration of nicotine along with alcohol is found to enhance the lipogenic tendency of alcohol in rats. PMID- 8500842 TI - Subcellular distribution of superoxide dismutase and catalase in human malarial parasite Plasmodium vivax. AB - Endogenous superoxide dismutase (SOD) has not been found to be present in P. vivax, a human malarial parasite and therefore it adopts and concentrates SOD from the host cell erythrocytes. It is demonstrated here that this adopted SOD from the host gets localized in lysosomes (10 k and 100 k fractions) of the malarial merozoites. P. vivax parasites were also found to contain very low levels of catalase, presumably as a result of contamination or adoption from the host red cell materials. It is therefore suggested that P. vivax merozoites are deficient in enzymes which are protective against the reactive oxygen species. PMID- 8500843 TI - Fetotoxic and teratogenic potential of substituted phenylurea herbicide, isoproturon, in rats. AB - Effect of isoproturon (0.225, 0.45 and 0.90 g/kg/day) administered (po) from day 6 through 15 of gestation was studied on pregnant rats and their offsprings. There were no distinct clinical signs other than dose-related depression and drowsiness of pregnant rats. None of the animals died due to toxicity of isoproturon. At higher doses, decreased maternal body weight was observed during the advanced stage of pregnancy. The litter size, fetal weight and crown-rump and transumbilical lengths were decreased. There was increase in fetal resorption frequency and the number of fetuses with stunted growth. The compound had no effect on fetal sex ratio. No major visceral and skeletal malformations were observed. The study indicates fetotoxic potential of the compound. PMID- 8500844 TI - Effect of felodipine on serum lipid profile in short term streptozotocin-diabetes in rats. AB - Lipid lowering effect of calcium antagonists is well documented in high fat fed rats and in hypertensive patients. In order to study their effect on lipid profile in experimental diabetes, felodipine 5 mg/kg/day per oral for 4 week was given to rats with streptozotocin-diabetes of 8 week duration. Serum total cholesterol and triglycerides were estimated in non-fasting rats at the end of the study period using Ranbaxy diagnostic kits. Diabetic rats had a significant elevation of both total cholesterol and triglycerides. In diabetic rats felodipine treatment produced a significant reduction of the serum triglycerides while there was no change in the serum total cholesterol. In control rats the drug did not produce any significant alteration in the levels of both total cholesterol and triglycerides. PMID- 8500845 TI - In vitro effect of 5-hydroxytryptamine on concanavalin-A agglutinability and multiplication of Entamoeba histolytica. AB - Six isolates of E. histolytica isolated and maintained by serial passage in modified Boeck and Drbohlav's medium were used in this study. When five of the isolates were grown in the above medium with 5-hydroxytryptamine (5-HT) added to the overlay, the agglutinability of the amoebae by concanavalin- A (con-A) was significantly increased compared to corresponding control cultures. Four isolates of E. histolytica grown with 5-HT had 1.5 to 2 times higher counts than the control cultures. Similarly the con-A agglutinability and counts of cultures of NIH-200 (an axenic strain of E.histolytica) were enhanced when grown in association with 5-HT. PMID- 8500846 TI - Effect of alpha-tocopherol on doxorubicin-induced changes in rat heart lysosomal enzymes. AB - Effect of doxorubicin on heart lysosomes were studied in rats with or without the administration of alpha-tocopherol. Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. alpha-tocopherol (400 mg/kg body wt) was co administered orally for 2 months. Activities of acid phosphatase, beta-D glucuronidase, cathepsin-D and beta-D-galactosidase were decreased in heart lysosomes but increased significantly in serum. A significant increase in lysosomal lipid peroxide level was noted. alpha-tocopherol co-administration reduced the lipid peroxide level as well as maintained the above mentioned enzyme activities. PMID- 8500847 TI - Dietary protein and cholesterol metabolism in small intestines. AB - Effect of quality and quantity of dietary protein on blood cholesterol and cholesterol metabolism in small intestines of rat was examined. Compared to casein, bengalgram in the diet decreased blood and intestinal cholesterol. It is suggested that this effect may be due to low levels of leucine in bengalgram protein and less release of insulin, an activator of HMG CoA Reductase. Low casein in the diet (12%) caused a decrease of blood and intestinal cholesterol while high casein in the diet (24%) caused a decrease of intestinal cholesterol only. It is suggested that both qualitywise and quantitywise, dietary protein influences body cholesterol. It is known that the nature and the quality of dietary fat and carbohydrates directly influence the metabolism of cholesterol. The dietary proteins might also have a significant role. Proteins are needed for the synthesis of enzymes required for the anabolism and catabolism of cholesterol and a few protein-aminoacids like leucine have a direct influence on cholesterol metabolism. Bengalgram was chosen for studying the effect of the quality of protein on cholesterol metabolism as there are reports in the literature that bengalgram feeding reduces blood cholesterol. Different amounts of casein containing diet were used in a separate set of experiments to investigate the effects of low and high protein diets on cholesterol metabolism i.e. quantitative effects of dietary protein. For many years, liver was enjoying the privilege of maintaining the homeostasis of blood cholesterol. Recently it has been shown that small intestines also synthesises considerable amounts of cholesterol. Hence, cholesterol metabolism was investigated separately in duodenum, jejunum and ileum. PMID- 8500848 TI - Influence of alpha-tocopherol on doxorubicin-induced lipid peroxidation, swelling and thiol depletion in rat heart mitochondria. AB - Effect of alpha-tocopherol on doxorubicin-induced swelling in rat heart mitochondria was studied in vitro. Mitochondria was isolated from control and alpha-tocopherol treated rats. Various concentrations of doxorubicin were added to mitochondrial suspension. Swelling, lipid peroxidation and thiol depletion were measured. Concentration and time dependent increase in swelling was noted with increase in lipid peroxidation and thiol depletion in mitochondria isolated from control rats. In alpha-tocopherol treatment, thiol depletion is significantly prevented with reduced lipid peroxidation and swelling. PMID- 8500849 TI - Effect of age on susceptibility of carcinogen benzidine-hydrochloride. AB - Susceptibility of carcinogen (benzidine hydrochloride) was checked by degranulation technique in rats of three different (young, adult and old) age groups. The dose response curves of these three different groups showed different per cent degranulation. Comparative data of dose response of benzidine hydrochloride observed on the basis of RNA/Protein ratio basis showed that old animals were more susceptible to carcinogens than young and adult animals. PMID- 8500850 TI - Rotavirus infection among children in Bombay. AB - From December 1984 to December 1986 samples of faeces were collected from 273 children and 50 adults suffering from acute diarrhea and from an equal number of control subjects. Presence of rotavirus was looked for by electron microscopy (EM), latex slide agglutination (LA) and enzyme-linked immunosorbent assay (ELISA). Of the 273 children 63 (23.0%) showed presence of rotavirus, with maximum incidence of 25.7% in 6 to 24 months age group. Out of 63 positive cases, 10 were associated with bacterial pathogens and 3 with protozoal--parasitic agents. In the remaining 50, rotavirus was the sole pathogen identified. Among the 273 age matched control children without diarrhoea only 3 (1.1%) showed presence of rotavirus. None of the adults showed presence of rotavirus. Rotavirus diarrhoea was more prevalent in cooler months of the year and in crowded houses. LA gave less number of positive results than ELISA but was cheaper and quicker. It is concluded that rotavirus is an important cause of infantile diarrhoea in Bombay. PMID- 8500851 TI - Blood pressure levels in diabetes mellitus. AB - Levels of fasting plasma glucose, body mass index, serum total lipids, serum total cholesterol, serum triglycerides and blood pressure of 177 Libyan diabetic patients were determined. The respective mean values were 212.4 +/- 5.6 mg/dl, 26.6 +/- 0.45 kg/m2, 825.7 +/- 20.5 mg/dl, 176.4 mg/dl, 144 +/- 5.8 mg/dl and 135.3 +/- 1.7/83 +/- 0.89 mm Hg. The mean levels of all variables except plasma glucose are significantly higher in the female patients than their male counterparts. Correlations were present between blood pressure levels and age/body mass index/serum total lipids. There was a significant correlation between systolic pressure levels and the duration of diabetes. Serum cholesterol and serum triglyceride levels correlated with diastolic blood pressure levels only. PMID- 8500852 TI - Primary leiomyoma of ovary. AB - Two cases of primary ovarian Leiomyoma are presented for their rarity. One of these cases clinically presented as an indirect inguinal hernia into labium majus a condition not reported earlier in the literature. PMID- 8500853 TI - Quality assurance in blood banks. PMID- 8500854 TI - Is endothelin involved in the pathogenesis of hypertension? AB - Endothelins are a family of potent vasoconstrictor peptides released by endothelial cells. The production of endothelin-1 (ET-1) can be stimulated by aggregating platelets and angiotensin II. It is inhibited by increases in intracellular concentration of cyclic GMP. ET-1 causes biphasic changes in arterial blood pressure and of peripheral resistance in several vascular beds: an initial transient decrease (due to release of nitric oxide, prostacyclin, or both from the endothelium) followed by a sustained increase (mainly due to direct activation of vascular smooth muscle). The vasoconstriction induced by the peptide is inhibited by increases in cyclic GMP. Few studies, except in pregnant women with preeclampsia or eclampsia, indicate that the circulating levels of the peptide are augmented in hypertension. Likewise, the information available on changes in responsiveness to endothelins in blood vessels from hypertensive animals is controversial. Until the effect of selective antagonists on the production or action of the peptide can be determined in hypertensive patients, caution must be exerted when implying a role for endothelin in the pathophysiology of hypertension. PMID- 8500855 TI - Potential role of endothelin in hypertension. Controversy on endothelin in hypertension. PMID- 8500856 TI - Renal morphological changes after sinoaortic denervation in dogs. AB - The present study investigates morphological renal lesions in sinoaortic denervated dogs 1 (n = 6) and 18 (n = 5) months after sinoaortic denervation compared with sham-operated controls (n = 8). After 1 month, a marked hyalinization and moderate thickening of the media of arterioles and small interlobular arteries were observed. These changes associated with edema and intimal thickening led to a narrowing of the lumen. In glomeruli, increase of mesangial matrix was focally present in all cases and associated with mesangial proliferation. In four of six cases, some glomeruli appeared retracted, with a large urinary space. A focal area of interstitial fibrosis occurred in just one case. After 18 months, similar but more pronounced vascular lesions were present, with marked hyperplasia of the media. Glomerular changes were characterized by mesangial lesions associated with focal glomerular sclerosis and thickening of Bowman's capsule. Tubulointerstitial lesions were more prominent in this group, with the presence of tubular epithelial changes and casts. Focal interstitial fibrosis, infiltrates, or both were demonstrated in all cases. These morphological lesions were associated with an increase in arterial blood pressure, proteinuria, and natriuresis and a decrease in urinary kallikrein. These results show that chronic sinoaortic denervation in dogs is associated with renal lesions similar to those observed in other well-established experimental and clinical hypertensive states. PMID- 8500857 TI - Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans. AB - To evaluate the role of the sodium pump in resistance control in vivo, we studied vascular responses to potassium, which produces vasodilation by the activation of vascular Na+, K(+)-ATPase, in normotensive volunteers receiving a high salt diet compared with volume-depleted subjects receiving diuretic treatment. Forearm blood flow was measured by strain-gauge plethysmography during small increments in local concentrations of potassium with intrabrachial arterial infusions of KCl. Infusions of 0.12 and 0.24 mEq/min KCl increased forearm blood flow and decreased forearm vascular resistance in a dose-dependent fashion. But the simultaneous intrabrachial arterial infusion of 2 micrograms/min ouabain, a Na+,K(+)-ATPase inhibitor, could blunt the decremental response of vascular resistance to 0.12 mEq/min KCl. The decrements of vascular resistance with KCl infusions divided by the initial resistance were significantly less with ouabain compared with those without ouabain (43 +/- 4% versus 57 +/- 3%, p < 0.01). This suggests that potassium produces vasodilation by the activation of vascular Na+,K(+)-ATPase activity. Similarly, salt loading (180 mEq NaCl for 7 days) after treatment with diuretics could attenuate percent decrements of resistance with KCl infusions (39 +/- 3% versus 53 +/- 2%, p < 0.01), whereas vascular resistance responses to sodium nitroprusside, a nonspecific vasodilator, and to verapamil, a calcium antagonist, did not change with salt loading after volume depletion. Therefore, salt loading could attenuate forearm vascular response to potassium specifically, as did the administration of ouabain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500858 TI - Sucrose does not raise blood pressure in rats maintained on a low salt intake. AB - Diets high in sucrose or fructose have been shown by others to induce a modest elevation of blood pressure in rats. The present experiments were conducted to determine whether the sucrose-induced increase of blood pressure is dependent on the intake of sodium chloride. Four groups of Sprague-Dawley rats were studied: 1) a group maintained on a low salt diet and distilled water (0.45% sodium chloride, no added sucrose), 2) a low salt-high sucrose group (0.45% sodium chloride diet and 7% sucrose in distilled water), 3) a high salt group (4% sodium chloride diet and distilled water), and 4) a high salt-high sucrose group on a diet adjusted daily to maintain the same high intakes of sodium chloride and sucrose as those of groups 2 and 3. Systolic blood pressures were measured by tail-cuff plethysmography during weeks 1-3 of treatment, and direct mean arterial blood pressures were recorded in conscious animals during week 4. Animals on the high salt diet gained weight more slowly than those on the low salt intake. On the low sodium chloride intake, blood pressures were not affected by high dietary sucrose (group 1 versus 2). In contrast, on the high sodium chloride intake, blood pressures were 10-14 mm Hg higher in sucrose-drinking animals than in water drinking animals (group 3 versus 4). The increments in blood pressures of the high sodium chloride-high sucrose group were not accompanied by greater increments in body weight compared with the animals on the high sodium chloride intake alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500859 TI - Captopril or conventional therapy in hypertensive type II diabetics. Three-year analysis. AB - The effects of long-term treatment with captopril and conventional therapy on albuminuria and metabolic parameters were compared in 74 hypertensive type II diabetics with normal serum creatinine. Patients were treated double-blind with either captopril monotherapy or combined with hydrochlorothiazide or therapy with metoprolol, hydrochlorothiazide, or both for 36 months. The treatment was titrated to achieve goal diastolic blood pressure of < or = 85 mm Hg. The reductions in blood pressures during treatment were similar in patients with (n = 21) and without (n = 53) microalbuminuria treated with either captopril or conventional therapy. No significant changes in albuminuria occurred in normoalbuminuric patients with either therapy. Although albuminuria fell in nearly all patients with microalbuminuria treated with captopril, it rose in eight of 12 patients on conventional therapy, with macroalbuminuria developing in two of them. Renal function was preserved by both types of treatment in both patient groups. Long-term treatment with either conventional therapy or captopril did not alter metabolic variables. We conclude that captopril alone or in combination decreases albuminuria and prevents the development of macroalbuminuria in hypertensive type II diabetics with persistent microalbuminuria. The renoprotective effect of this agent, however, remains to be demonstrated with longer term data on renal function. Aggressive antihypertensive treatment with either captopril or conventional therapy appears to be effective in preventing the onset of microalbuminuria in most normoalbuminuric patients. In contrast, with previous short-term studies, the use of converting enzyme inhibitors or conventional therapy did not cause adverse metabolic effects. PMID- 8500860 TI - Effect of diltiazem on glomerular heparan sulfate and albuminuria in diabetic rats. AB - Calcium entry blockers, particularly diltiazem, have been shown to lower not only systemic blood pressure but also improve proteinuria in non-insulin-dependent diabetic patients. The presence of proteinuria is attributed to the loss of glomerular heparan sulfate, which confers a negative charge on the basement membrane. In the present study, we evaluated the efficacy of diltiazem in lowering blood pressure and proteinuria in diabetic rats and also examined the possibility that diltiazem prevents proteinuria through glomerular preservation of heparan sulfate. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg). One group of diabetic rats was treated with diltiazem (25 mg/L) in drinking water for 20 weeks. Another group of diabetic rats and a group of nondiabetic rats were given tap water only. Systolic blood pressure was measured at 4, 8, 12, and 20 weeks. Urinary excretion of albumin was done at 4, 8, 12, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of [35S]sulfate. Diltiazem lowered blood pressure significantly in diabetic rats at 8, 12, and 20 weeks. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from normal rats. Characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Diltiazem therapy returned not only glomerular synthesis but also various fractions of heparan sulfate to normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500861 TI - Atrial natriuretic peptide in non-modulating essential hypertension. AB - To evaluate the atrial natriuretic peptide response to angiotensin II (Ang II) infusion in non-modulating hypertension, we studied 31 men with essential hypertension. These patients were subdivided into groups of low renin patients (n = 8), non-modulators (n = 11), and modulators (n = 12) according to their renin profile and ability to modulate renin and aldosterone responses to a graded infusion of Ang II (1.0 and 3.0 ng/kg per minute) on a low Na+ intake (10 mmol Na+ per day). During basal conditions, plasma atrial natriuretic peptide was higher (p < 0.05) in low renin patients (16.34 +/- 2.67 fmol/mL) than in both modulators (10.59 +/- 4.29 fmol/mL) and non-modulators (9.85 +/- 2.64 fmol/mL). During Ang II infusion, plasma atrial natriuretic peptide significantly increased in both low renin (27.67 +/- 2.61 fmol/mL at 60 minutes, p < 0.01) and modulating (20.36 +/- 3.07 fmol/mL at 60 minutes, p < 0.05) patients, whereas it did not change in non-modulators (13.94 +/- 4.39 fmol/mL, NS). After 5 days on a high sodium intake (200 mmol Na+ per day), plasma atrial natriuretic peptide rose in modulating (20.61 +/- 2.31 fmol/mL, p < 0.01 versus low sodium intake), non modulating (20.11 +/- 6.48 fmol/mL, p < 0.01 versus low sodium intake), and low renin (26.13 +/- 3.81 fmol/mL, p < 0.001 versus low sodium intake) hypertensive patients. When the Ang II infusion was repeated with a high sodium intake, plasma atrial natriuretic peptide increased again in low renin and modulating patients, whereas it did not change in non-modulators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500862 TI - Microalbuminuria in essential hypertension. Reduction by different antihypertensive drugs. AB - The effects of four different antihypertensive drugs (the Ca(2+)-channel blocker felodipine, the beta-blocker metoprolol, the angiotensin converting enzyme inhibitor ramipril, and the alpha-blocking agent doxazosin) on microalbuminuria and renal hemodynamics were evaluated in a double-blind, crossover study in 17 patients (10 women, seven men, aged 39 +/- 14 years) with mild-to-moderate essential arterial hypertension and microalbuminuria. Patients were studied after a 2-week placebo phase preceded by 2 weeks off all medication and after 12 weeks of treatment with each drug. Between each drug treatment, there was another 14 day placebo washout period. At the end of the study, we performed two additional 2-week placebo periods. After each placebo and treatment period, we measured albumin excretion during a 3-day collecting period. Renal hemodynamics were assessed by clearance techniques (inulin and p-aminohippurate clearance) at the end of the first and last placebo periods and after each treatment period. All drugs reduced mean arterial pressure and microalbuminuria to a similar and statistically significant (p < 0.05) extent (mean arterial pressure: placebo phase, 116 +/- 5 mm Hg; felodipine, 101 +/- 4 mm Hg; metoprolol, 101 +/- 5 mm Hg; ramipril, 101 +/- 4 mm Hg; doxazosin, 102 +/- 5 mm Hg; urinary albumin excretion: placebo phase, 46 +/- 50 mg/day; felodipine, 18 +/- 23 mg/day; metoprolol, 14 +/- 12 mg/day; ramipril, 16 +/- 16 mg/day; doxazosin, 14 +/- 14 mg/day). Mean arterial pressure levels and urinary albumin excretion returned to baseline after the last placebo period (110 +/- 6 mm Hg and 40 +/- 46 mg/day, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500863 TI - Mechanics and composition of cerebral arterioles in renal and spontaneously hypertensive rats. AB - The purpose of this study was to examine effects of hypertension on mechanics of cerebral arterioles in nongenetic and genetic models of chronic hypertension. Pressure (servo null) and diameter were measured in pial arterioles of anesthetized renal hypertensive rats (one-kidney, one clip), uninephrectomized normotensive rats, spontaneously hypertensive rats, and normotensive Wistar-Kyoto rats. During maximal dilatation with EDTA, external diameter of pial arterioles at 70 mm Hg pial arteriolar pressure was not significantly different in renal hypertensive and normotensive rats (86 +/- 5 [mean +/- SEM] versus 84 +/- 4 microns) but was less in spontaneously hypertensive rats than in Wistar-Kyoto rats (81 +/- 3 versus 92 +/- 3 microns; p < 0.05). Cross-sectional area of the arteriolar wall (histological) was greater in renal hypertensive than in normotensive rats (1,360 +/- 131 versus 952 +/- 89 microns 2; p < 0.05) and in spontaneously hypertensive rats than in Wistar-Kyoto rats (1,294 +/- 97 versus 817 +/- 86 microns 2; p < 0.05). The stress-strain relation obtained from pressure-diameter data during maximal dilatation with EDTA indicated that distensibility of pial arterioles, when fully relaxed, was greater in renal hypertensive and spontaneously hypertensive rats than in normotensive and Wistar Kyoto rats. We used point-counting stereology to quantitate composition of pial arterioles in renal hypertensive rats. Cross-sectional area of smooth muscle and elastin was significantly greater in renal hypertensive than in normotensive rats (smooth muscle, 947 +/- 108 versus 620 +/- 62 microns 2; elastin, 101 +/- 11 versus 55 +/- 6 microns 2; p < 0.05), whereas cross-sectional area of collagen and basement membrane was not significantly different in the two groups (collagen, 6 +/- 1 versus 5 +/- 1 microns 2; basement membrane, 120 +/- 12 versus 104 +/- 8 microns 2). Thus, we conclude that 1) cerebral arterioles undergo hypertrophy in both renal hypertensive and spontaneously hypertensive rats; 2) cerebral arterioles in renal hypertensive rats do not undergo "remodeling" with a reduction in external diameter, whereas external diameter is smaller in spontaneously hypertensive than in Wistar-Kyoto rats; 3) distensibility of cerebral arterioles, when fully relaxed, is increased in renal hypertensive rats and is greater in spontaneously hypertensive than in Wistar-Kyoto rats; and 4) the distensible components of the arteriolar wall are increased disproportionately in cerebral arterioles of renal hypertensive rats, which may contribute to increases in arteriolar distensibility. PMID- 8500864 TI - Psychophysiological reactivity and cardiac end-organ changes in white coat hypertension. AB - This study aimed 1) to assess whether patients with an exaggerated blood pressure response to the doctor's presence ("white coat" effect) also display a pattern of enhanced blood pressure reactivity to mental stress and physical exercise and 2) to determine the presence of left ventricular structural and filling abnormalities in patients with white coat hypertension. We studied 56 (40 men) consecutive patients (mean [SD] age, 46.4 [9.1] years) whose clinic blood pressure was repeatedly high. Patients were classified as having white coat hypertension (n = 20) if both their mean daytime (from 7 AM to 11 PM) ambulatory systolic and diastolic blood pressures were less than 134 and 90 mm Hg, respectively. Patients were considered to have persistent hypertension (n = 36) if daytime systolic blood pressure was 134 mm Hg or more or diastolic blood pressure was 90 mm Hg or more. Eighteen subjects with clinic blood pressure lower than 140/90 mm Hg served as a normotensive control group. Blood pressure reactivity from baseline to mental arithmetic, isometric handgrip, and cycle ergometry did not display any difference among the three groups. The white coat hypertensive group had left ventricular mass index lower than the persistent hypertensive group but higher than the normotensive group. Doppler indexes of left ventricular diastolic filling displayed similar abnormalities in the white coat and persistent hypertensive groups compared with the normotensive group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500865 TI - Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs. AB - The present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamics and renin release in the canine nonfiltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (p < 0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 +/- 1.3 to 67.4 +/- 1.2 mm Hg. However, with a higher rate of endothelin-1 infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5 +/- 1.3 and 51.5 +/ 1.8 mm Hg (p < 0.01), whereas renal blood flow was reduced from 154.5 +/- 15 to 83.0 +/- 9.5 and 53.5 +/- 9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9 +/- 5.6 to 26.6 +/- 4.9 units/min per gram kidney weight (p < 0.01), and it fell further to 16.1 +/- 4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500866 TI - Accuracy of a continuous blood pressure monitor based on arterial tonometry. AB - A validation study of the continuous noninvasive tonometric blood pressure monitor called JENTOW was performed in 20 normotensive subjects and 10 hypertensive patients. Tonometric and intra-arterial blood pressures were simultaneously recorded at supine rest and during a Valsalva maneuver and tilting test. The results of the strict evaluation of the instrument's capacity for reproducing intra-arterial blood pressure were as follows: 1) The overall frequency response of the transcutaneous blood pressure-monitoring system based on arterial tonometry was flat, with negligible delay to intra-arterial blood pressure in the range of 0-5 Hz. 2) The largest discrepancy between intra arterial and tonometric pressure waveforms was found at the early systolic phase; except for this phase, the tonometric waveform was almost equal to the intra arterial waveform. 3) The beat-to-beat variability of tonometric pressure corresponded to that of intra-arterial pressure almost perfectly in the physiologically significant frequency range of 0-0.5 Hz. 4) During resting conditions, the averages of the systolic and diastolic values measured tonometrically corresponded well to those measured intra-arterially. 5) The changes in the between-method discrepancy of blood pressure values during the Valsalva maneuver were statistically significant but small (< 5 mm Hg). 6) No significant effect of postural tilting was found on the between-method discrepancy. We conclude that this method is clinically acceptable and reliable except for its limited capacity for recording the higher frequency intra-arterial waveform and for responding to the relatively rapid and large transient changes in blood pressure. PMID- 8500867 TI - Enhanced blood pressure response to cyclooxygenase inhibition in salt-sensitive human essential hypertension. AB - To evaluate the influence of salt sensitivity on the blood pressure response to oral indomethacin treatment, we studied 35 hospitalized essential hypertensive patients (24 men and 11 women, aged from 40 to 55 years). During a normal NaCl intake (120 mmol Na+ per day), patients were assigned to receive in a randomized double-blind fashion either 200 mg indomethacin (25 patients) or placebo (10 patients) for 5 days. Two weeks after the interruption of indomethacin treatment, during which the normal NaCl intake was continued, salt sensitivity was assessed by giving each patient a high (220 mmol Na+ per day for 10 days) and then a low (20 mmol Na+ per day for 10 days) NaCl diet. Blood pressure changes were evaluated, and the measurement taken at the end of the 2 weeks under normal sodium intake was considered baseline blood pressure. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both low and high periods of sodium intake. In salt-resistant patients treated with indomethacin (n = 12, nine men and three women, mean age 50.5 +/- 3.7 years), neither blood pressure (systolic blood pressure from 150.8 +/- 11.2 to 154.6 +/- 9.3 mm Hg, NS; diastolic blood pressure from 99.3 +/- 2.1 to 101.1 +/- 4.4 mm Hg, NS) nor the urinary Na+ excretion (from 108.1 +/- 20.9 to 97.9 +/- 9.1 mmol/24 hr, NS) was significantly affected by the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500868 TI - Bacterial antigenic variation, host immune response, and pathogen-host coevolution. PMID- 8500869 TI - Role of M protein in pharyngeal colonization by group A streptococci in rats. AB - As the initial step in infection, group A streptococci (GAS) colonize either the nasopharyngeal mucosa or the skin of humans. A number of virulence factors have been implicated in the colonization phase of pathogenesis based upon their in vitro activities, but the in vivo data supporting their role in colonization of the host tissues is lacking. In this investigation, the potential requirement for M protein in pharyngeal colonization by GAS was explored by using near-isogenic strains in experimental animals studies. Fischer rats were infected by intranasal and oral inoculation with both M-positive and M-negative Streptococcus pyogenes strains. Colonization of the pharyngeal area by the streptococci was monitored at various time intervals. Both M-positive and M-negative strains colonized during the first week following infection, indicating that M protein was not necessary for this initial colonization. Two M-positive strains of S. pyogenes were recovered from the rats up to 23 weeks following inoculation, while the colonization levels for M-negative strains decreased rapidly in the second and third weeks, becoming negligible by the fourth week. This indicates a potential role for M protein in the persistence of colonization at this mucosal surface. Colonization of rats with either M-positive strain of S. pyogenes also resulted in the appearance of salivary and serum antibody responses. This in vivo model should allow further investigation into factors required for GAS disease, including the examination of the potential role of the host immune response both in modulation of the pharyngeal surface and in modulation of antigenic changes in M protein or other surface factors. PMID- 8500870 TI - Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection in mice. AB - Resistance against acute and chronic infection with Taxoplasma gondii in BALB/c and CBA/Ca mice was compared. Intraperitoneal inoculation of either 20, 40, or 80 cysts of the ME49 strain resulted in mortality rates in BALB/c mice of 12% (2 of 17), 50% (6 of 12), and 75% (9 of 12), respectively, within 3 weeks after infection (acute stage). There was no mortality in the CBA/Ca mice for any of the doses. In marked contrast, CBA/Ca mice were highly sensitive to chronic infection with developing toxoplasmic encephalitis; they began dying 2 months after infection with 10 cysts of the ME49 strain, and mortality reached 53% (16 of 30) by the sixth month postinfection. No mortality (0 of 20) was observed in the chronically infected BALB/c mice. CBA/Ca mice had markedly more cysts in their brains than BALB/c mice in the chronic stage. Severe inflammatory changes were observed only in the brains of CBA/Ca mice. Interestingly, in the acute stage (the first 3 weeks), numbers of cysts in the brains were significantly greater in CBA/Ca than BALB/c mice, whereas only BALB/c mice showed mortality in that time period. No inflammatory changes were observed in brains of BALB/c mice during the acute stage of the infection. Thus, resistance against chronic infection appears to be regulated by a mechanism(s) that is different from those conferring resistance against acute infection. There was no difference in gamma interferon levels in sera between CBA/Ca and BALB/c mice during the acute stage. However, during the chronic stage, only BALB/c mice had detectable levels of gamma interferon in their sera. PMID- 8500871 TI - Development of a trehalose 6,6'-dimycolate model which explains cord formation by Mycobacterium tuberculosis. AB - Trehalose 6,6'-dimycolate (TDM) is a glycolipid of mycobacteria that displays an unusual toxicity and has been reported to be a virulence factor for Mycobacterium tuberculosis. Lack of understanding of the toxicity has impeded acceptance of TDM as a virulence factor. We previously reported that the toxicity of TDM depends on its presentation as a surface monolayer consisting of 30% trehalose and 70% exposed mycolic acid moieties. This paper further investigates the structure of the TDM monolayer. It began with the observation that beads coated with TDM, but not with closely related analogs, aggregate to form organized structures resembling the cords of virulent mycobacteria. This implied that the TDM molecules in the monolayer were arranged in an organized structure. This structure was investigated by real-time kinetic microscopy, scanning electron microscopy, and gross observations of the adhesion patterns of TDM-coated beads. In each of these models, the structures induced by TDM differed from those of analogs or other amphiphiles studied. These observations were used to construct a model of the structure of TDM monolayer which envisions linear arrays of TDM molecules arranged in a circumferential pattern on beads with discontinuities only at the two poles. PMID- 8500872 TI - Immunocompromise in gnotobiotic pigs induced by verotoxin-producing Escherichia coli (O111:NM). AB - A verotoxin-producing Escherichia coli serotype O111:NM strain (strain 10049; verotoxin 1 positive) persistently infected experimentally inoculated gnotobiotic pigs, causing attaching-effecting intestinal lesions and chronic diarrhea. Experiments were performed to determine whether persistent infection might be associated with immunocompromise of the host of this organism. Pigs inoculated with this strain had a significant reduction in peripheral blood lymphocytes and lower antibody titers to sheep erythrocytes compared with control pigs. Compared with pigs given a verotoxin-negative pathogenic strain of the same serotype (O111:NM, strain 2430), pigs inoculated with the verotoxin-positive strain had lower peripheral lymphocyte counts and proliferative responses to concanavalin A, phytohemagglutinin, and pokeweed mitogens. The results of this study suggest that strain 10049 has an immunocompromising effect on gnotobiotic pigs. PMID- 8500873 TI - Local and systemic immune responses in murine Helicobacter felis active chronic gastritis. AB - Helicobacter felis inoculated per os into germfree mice and their conventional non-germfree counterparts caused a persistent chronic gastritis of approximately 1 year in duration. Mononuclear leukocytes were the predominant inflammatory cell throughout the study, although polymorphonuclear cell infiltrates were detected as well. Immunohistochemical analyses of gastric mucosa from H. felis-infected mice revealed the presence of mucosal B220+ cells coalescing into lymphoid follicles surrounded by aggregates of Thy-1.2+ T cells; CD4+, CD5+, and alpha beta T cells predominated in organized gastric mucosal and submucosal lymphoid tissue, and CD11b+ cells occurred frequently in the mucosa. Follicular B cells comprised immunoglobulin M+ (IgM+) and IgA+ cells. Numerous IgA-producing B cells were present in the gastric glands, the lamina propria, and gastric epithelium. Infected animals developed anti-H. felis serum IgM antibody responses up to 8 weeks postinfection and significant levels of IgG anti-H. felis antibody in serum, which remained elevated throughout the 50-week course of the study. PMID- 8500874 TI - Characterization of pertussis toxin analogs containing mutations in B-oligomer subunits. AB - The S2, S3, and S4 subunit genes of pertussis toxin (PT) from Bordetella pertussis were subjected to site-directed mutagenesis, and the resultant PT analogs were assayed for altered biological properties. PT analogs S2(T91,R92,N93) delta and S2(Y102A,Y103A) exhibited reduced binding to fetuin. Several PT analogs with mutations in the S2, S3, or S4 subunit showed reduced in vitro toxicity, as measured in the Chinese hamster ovary (CHO) cell clustering assay. In particular, PT analogs S3(Y82A) and S3(I91,Y92,K93) delta retained 10% or less residual toxicity. These mutants also exhibited significantly lower mitogenic and hemagglutinating activities and reduced in vivo activities, as measured by the histamine sensitization and leukocytosis assays. The S4(K54A,K57A) PT analog had significantly reduced CHO cell clustering activity, though other biological activities remained unaffected. PT analogs S1(E129G)/S3(Y82A) and S1(E129G)/S3(I91,Y92,K93) delta displayed a cumulative effect of the S1 and S3 mutations for both in vitro and in vivo toxic activities. These PT analogs, as well as S1(R9K,E129G)/S3(K82A) and S1(R9K,E129G)/S3(I91,Y92,K93) delta, still expressed an epitope which elicits a neutralizing antitoxin antibody and were protective in the mouse intracerebral challenge test. Recombinant pertussis vaccines based on PT analogs with detoxifying mutations in multiple subunits may thus represent the next generation of improved whooping cough vaccines. PMID- 8500875 TI - Adhesion of Yersinia enterocolitica to purified rabbit and human intestinal mucin. AB - Interactions between Yersinia enterocolitica and purified intestinal mucins from rabbit and humans were investigated. Plasmid-bearing virulent organisms (but not plasmid-free nonvirulent bacteria) bound well to both mucins, suggesting that adherence was controlled by the virulence plasmid. Examination of binding to 14 different preparations of purified human intestinal mucin (8 preparations obtained from normal subjects and 6 samples from patients with cystic fibrosis) revealed no differences between normal and cystic fibrotic mucins in ability to serve as a binding substrate for virulent Y. enterocolitica. Analyses of binding curves suggested the presence of a single type of noninteracting receptor for Y. enterocolitica in both rabbit and human mucins with similar (but not necessarily identical) structures. Virulent bacteria bound to polystyrene through hydrophobic interactions that could be disrupted by treating the organisms with tetramethyl urea. In contrast, binding of plasmid-bearing Y. enterocolitica to intestinal mucin was not susceptible to tetramethyl urea and therefore does not appear to involve hydrophobic interactions. Prior incubation of organisms with mucin significantly inhibited binding to polystyrene, suggesting that mucin can mask hydrophobic adhesins on the bacterial surface. Hapten inhibition studies revealed that the monosaccharides galactose and N-acetylgalactosamine and the disaccharide lactose could markedly reduce (but not abolish) bacterial adherence to mucin but other monosaccharides and the RGD peptide had no effect on mucin binding. We conclude that virulent Y. enterocolitica is capable of interacting with the carbohydrate moiety of intestinal mucin. These interactions appear to be plasmid mediated and not hydrophobic. PMID- 8500876 TI - Evidence for possible involvement of an elastolytic serine protease in aspergillosis. AB - A number of isolates of Aspergillus fumigatus obtained from the hospital environment produced extracellular elastolytic activity. This activity was found to be catalyzed by a single 33-kDa protein which was purified and characterized to be a serine protease. A. fumigatus, when grown on the insoluble structural material obtained from murine and bovine lung, produced the same extracellular 33 kDa elastolytic protease, indicating that this enzyme is likely to be produced when the organism infects the lung. Polymerase chain reaction with an oligonucleotide primer based on the N-terminal amino acid sequence of the elastolytic enzyme yielded a cDNA which was cloned and sequenced. The active serine motif showed more similarity to subtilisin than to mammalian elastase. The amino acid sequence showed 80% identity to the alkaline protease from Aspergillus oryzae. Screening of hospital isolates of Aspergillus flavus showed great variation in the production of elastolytic activity and a much lower level of activity than that produced by A. fumigatus. The elastolytic protease from A. flavus was shown to be a serine protease susceptible to modification and inactivation by active serine and histidine-directed reagents. This protease cross-reacted with the antibodies prepared against the elastolytic protease from A. fumigatus. Immunogold localization of the elastolytic enzyme showed that A. fumigatus germinating and penetrating into the lungs of neutropenic mice secreted the elastolytic protease. An elastase-deficient mutant generated from a highly virulent isolate of A. fumigatus caused drastically reduced mortality when nasally introduced into the lung of neutropenic mice. All of the evidence suggests that extracellular elastolytic protease is a significant virulence factor in invasive aspergillosis. PMID- 8500877 TI - Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. AB - Immunity against shigellosis has been shown to correlate with the presence of antibodies specific for Shigella lipopolysaccharide (LPS). We here propose a new candidate vaccine for shigellosis composed of purified Shigella flexneri 2a or Shigella sonnei LPS hydrophobically complexed with group C type 2b Neisseria meningitidis outer membrane protein proteosomes. Immunization of mice either orally or intranasally with this complex induced specific homologous anti-LPS antibodies in both intestinal and respiratory secretions as well as in sera. Strong anamnestic responses were found after two or three immunizations. LPS alone, alkaline-detoxified LPS, or alkaline-detoxified LPS complexed with proteosomes was not effective. Oral or intranasal immunization of guinea pigs with two or more doses of this proteosome-LPS vaccine elicited homologous protection against Shigella keratoconjunctivitis (Sereny test). These data demonstrate that proteosomes can be used as an effective mucosal vaccine delivery system and that orally or intranasally administered acellular vaccines can protect against Shigella infections. PMID- 8500878 TI - Rapid dissemination by the agent of Lyme disease in hosts that permit fulminating infection. AB - We determined whether the agent of Lyme disease (Borrelia burgdorferi) disseminates more rapidly following deposition in hosts that permit fulminating infection than in hosts in which infection is relatively benign. Thus, individual infected nymphal deer ticks (Ixodes dammini) were permitted to engorge on the ears of C3H mice, and the site of attachment was excised at intervals thereafter. Infection in each mouse was determined by serology and by examining previously noninfected ticks that had engorged on these mice. These results were compared with data obtained similarly by using the CD-1 strain of mice in which the agent is relatively nonpathogenic. When the site of inoculation was ablated within 2 days after the infected tick became replete, dissemination was aborted. Spirochetemia could not be demonstrated in any of these mice. We conclude that Lyme disease spirochetes disseminate from the feeding lesion of an infecting tick more rapidly in certain highly spirochete-susceptible mice than in others in which pathogenesis is less severe. PMID- 8500879 TI - Immunoglobulin class and subclass distribution of antibodies reactive with the immunodominant antigen of Actinobacillus actinomycetemcomitans serotype b. AB - The aims of this study were to determine the immunodominant antigens of Actinobacillus actinomycetemcomitans serotype b (Aab) for the different immunoglobulin (Ig) classes and subclasses and to determine the relative levels of these different Igs in serum. Seropositive early-onset periodontitis patients were sampled, and the Ig classes IgG, IgA, and IgM and subclasses IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 were studied. Reactivity with Aab antigens was assessed by using the Western blot (immunoblot) in limiting dilution analysis and radioimmunoassay with sera from 13 early-onset periodontitis subjects. A smeared antigen in the upper portion of the immunoblots, typical of high-molecular-weight LPS, was immunodominant for IgG, IgA, IgM, IgG1, IgG2, IgG3, IgA1, and IgA2. This smeared antigen was present in every patient for all of these Igs at the endpoint. A few additional antigens were also present at the endpoint in some patients, but none were present in more than half of the subjects. The distribution of antibody titers by Ig classes reactive with the Aab immunodominant antigen was IgG > IgA > IgM. The distribution of antibody titers by IgG subclass was IgG2 > IgG1 approximately IgG3. Further quantitation by radioimmunoassay revealed that the mean concentration of IgG2 (65.7 micrograms/ml) was significantly greater than that of IgG1 (8.8 micrograms/ml). The IgA subclass distribution was IgA1 >> IgA2, with IgA1 apparently being second only to IgG2. Therefore, the Aab antigen eliciting the highest antibody level in virtually all Ig classes and subclasses appeared to be lipopolysaccharide, and IgG2 was markedly elevated over all other serum Ig classes or subclasses reactive with Aab. PMID- 8500880 TI - Concomitant loss of conformation and superantigenic activity of staphylococcal enterotoxin B deletion mutant proteins. AB - The T-cell-stimulating activity of staphylococcal enterotoxin B (SEB) is an important factor in the pathogenesis of certain staphylococcal diseases. To investigate the immunologically active domains of the SEB molecule, we have produced truncated fragments of recombinant SEB by C-terminal and N-terminal deletions. The fragments were expressed as fusion proteins with protein A, including a cleavage site to remove the protein A part. Mutant proteins were tested for the ability to stimulate human resting T cells and SEB-reactive T-cell clones. Deletion of only 9 amino acids from the C terminus leads to complete loss of T-cell-stimulating activity. Removing further amino acids from the SEB molecule did not lead to a reexpression of T-cell-mitogenic activity. A mutant protein, however, in which the 9 C-terminal amino acids were replaced with a tail of 68 amino acids encoded by the vector was fully active. Two mutant proteins with N-terminal deletions of 60 and 81 amino acids were inactive as well. A neutralizing monoclonal antibody against a conformational epitope lost binding with all the inactive mutant proteins only, whereas a monoclonal antibody recognizing an epitope involved in emetic activity reacted with all mutant proteins. These results suggest that even small deletions at the C terminus affect the three-dimensional conformation of the SEB molecule. PMID- 8500881 TI - In vivo production of exotoxin A and its role in endogenous Pseudomonas aeruginosa septicemia in mice. AB - We have examined the production of Pseudomonas aeruginosa exotoxin A (ETA) and its role in endogenous bacteremia in mice. Mice given P. aeruginosa D4 orally died of bacteremia between days 10 and 13 following cyclophosphamide-induced leukocytopenia. In this model, serum endotoxin was detected beginning on day 7 by the Limulus assay and P. aeruginosa was cultured from blood beginning on day 9. ETA and tumor necrosis factor alpha (TNF) were also detected in serum by enzyme linked immunosorbent assay beginning on day 9. Purified ETA did not stimulate the production of TNF in normal mice primed with a synthetic derivative of muramyl dipeptide in the absence of endotoxin. However, ETA enhanced and primed endotoxin induced TNF production in mice. The mortality rate of mice given ETA mutant PAO PRI (5.0%) was significantly lower than that of mice given the parent strain (78.8%). These data indicate that ETA may be an important factor in the occurrence of P. aeruginosa bacteremia and/or the death of mice. Also, ETA may be responsible for enhancing the production of a lethal dose of TNF in the presence of endotoxin in P. aeruginosa bacteremia. PMID- 8500882 TI - Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori. AB - Our previous work has shown that Helicobacter pylori specifically recognizes gangliotetraosylceramide, gangliotriaosylceramide, and phosphatidylethanolamine in vitro. This binding specificity is shared by exoenzyme S from Pseudomonas aeruginosa, and monoclonal antibodies against this adhesin prevent the attachment of H. pylori to its lipid receptors. We now report the use of a novel, versatile affinity matrix to purify a 63-kDa exoenzyme S-like adhesin from H. pylori which is responsible for the lipid-binding specificity of this organism. PMID- 8500883 TI - Identification of a Staphylococcus aureus extracellular matrix-binding protein with broad specificity. AB - A staphylococal surface protein capable of binding several extracellular matrix glycoproteins was purified as a result of our attempts to identify a receptor(s) for bone sialoprotein (BSP) on Staphylococcus aureus cells. Proteins from different staphylococcal strains were solubilized in sodium lauryl sulfate, separated by polyacrylamide gel electrophoresis, blotted onto Immobilon P membranes, and probed with 125I-BSP. Several bacterial proteins bound the radiolabeled ligand, and various strains expressed different repertoirs of BSP binding proteins. Major BSP-binding proteins with apparent M(r)s of 72,000 or 60,000 were present on most strains, and these proteins were further studied. The 72- and 60-kDa proteins were preferentially expressed when bacteria were cultured in Luria broth compared with when they were cultured on tryptic soy broth, and the abundance of the proteins could be correlated to an increased 125I-BSP binding. Both the 72-kDa and the 60-kDa proteins were solubilized by extraction of cells with 1 M LiCl and were purified by cation-exchange chromatography. Amino acid composition analysis of the purified 72-kDa protein indicated a high content of lysine (11.9%) and hydrophobic amino acids (28.0% combined). In Western ligand blotting (immunoblotting) experiments, the 72-kDa protein bound not only BSP but also radiolabeled fibronectin, fibrinogen, vitronectin, thrombospondin, and, to some extent, collagen. Addition of the purified 60-kDa protein to S. aureus cells did not inhibit binding of the different ligands but in some cases resulted in an augmentation of the binding of 125I-ligand. Purified 60-kDa protein could hemagglutinate sheep erythrocytes at a concentration of 61 micrograms/ml. The agglutination reaction was inhibited by high concentrations of fucose, mannose, or melibiose. These data suggest that the purified proteins may serve as bacterial receptors with broad specificity for matrix glycoproteins and that the proteins may act as carbohydrate-binding proteins. PMID- 8500884 TI - Attaching and effacing locus of a Citrobacter freundii biotype that causes transmissible murine colonic hyperplasia. AB - Citrobacter freundii biotype 4280 produces attaching and effacing (AE) lesions in the large intestine of laboratory mice and is the causative agent of transmissible murine colonic hyperplasia. AE lesions are also produced by enteropathogenic Escherichia coli in humans. Southern analysis revealed that biotype 4280, but not 20 other strains of C. freundii, contained DNA homologous to the eae (E. coli attaching and effacing) gene which is necessary for AE activity by enteropathogenic E. coli in vitro. We have cloned and determined the nucleotide sequence of the C. freundii eae homolog. Our findings suggest that the eae locus of C. freundii biotype 4280 is necessary for AE activity and has a role in the pathogenesis of transmissible murine colonic hyperplasia. PMID- 8500885 TI - Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites. AB - Passive transfer of monoclonal antibodies (MAbs) against malaria circumsporozoite (CS) proteins protects animals against malaria. Active immunization with synthetic or recombinant peptides induces a level of polyclonal antibodies to sporozoites comparable to those found after passive immunization but does not provide comparable protection. In the Plasmodium yoelii system, synthetic or recombinant peptide-induced antibodies have never been shown to protect. The current studies were designed to determine whether immunogen structure (native protein versus synthetic peptide) or immunoglobulin G (IgG) subclass of antibodies was responsible for the absolute differences between protective, passively transferred MAbs and nonprotective, actively induced polyclonal antibodies. In this study we produced two MAbs, QGP-S1 (IgG1) and QGP-S2 (IgG2b), by immunization with a synthetic peptide based on the P. yoelii CS major repeat, (QGPGAP)4, conjugated to keyhole limpet hemocyanin. These MAbs were compared tp NYS1 (IgG3), an anti-CS protein MAb previously produced by immunization with irradiated P. yoelii sporozoites, which recognizes (QGP GAP)2. QGP-S1 and QGP-S2 passively transferred protection. However, when compared with NYS1, there was a hierarchy of protection, NYS1 > QGP-S1 > QGP-S2. There was no correlation between antibody level at challenge as determined by immunofluorescent antibody test against sporozoites or enzyme-linked immunosorbent assay against (QGPGAP)2 or apparent antibody avidity for (QGPGAP)2 by sodium thiocyanate elution assay. The data demonstrate that a synthetic peptide can induce protective antibodies and that a specific antibody subclass is not required for protection. Work to determine whether antibody affinity or fine specificity can explain the hierarchy of protection among the MAbs is under way. PMID- 8500886 TI - The putative arthritogenic cationic 19-kilodalton antigen of Yersinia enterocolitica is a urease beta-subunit. AB - The gene coding for a putative 19-kDa arthritogenic antigen of Yersinia enterocolitica O:3 (A. K. H. Mertz et al., J. Clin. Invest. 87:632-642, 1991) was cloned and sequenced after amplification of part of the gene by the polymerase chain reaction using degenerate primers, inferred from the amino acid sequence. The deduced amino acid sequence of the antigen showed similarity to small subunits of ureases from several different organisms, including the jack bean urease. Screening of a genomic library of Y. enterocolitica O:3 with a 19-kDa antigen-specific DNA probe allowed recombinant clones containing the entire urease operon to be obtained. These clones expressed urease activity in Escherichia coli. PMID- 8500887 TI - Outer membrane protein YadA of enteropathogenic yersiniae mediates specific binding to cellular but not plasma fibronectin. AB - The binding of bacteria or bacterial products to host proteins of tissue extracellular matrix may be a mechanism of tissue adherence. We investigated interactions of the plasmid-encoded outer membrane protein YadA, which confers pathogenic functions on enteropathogenic yersiniae, with fibronectin. Attachment of YadA-positive and YadA-negative recombinant Yersinia enterocolitica strains to cartilage-derived human cellular fibronectin and human plasma fibronectin in the solid phase revealed that YadA mediates binding of yersiniae to cellular fibronectin in a saturable, concentration-dependent manner. The interaction could be inhibited by an anti-YadA-specific anti-serum. An anti-beta 1-integrin antibody and the synthetic peptide G-R-G-D-S-P, representing the binding site for alpha 5 beta 1-integrin on fibronectin, did not block attachment of YadA-positive yersiniae to cellular fibronectin, indicating a binding site for YadA on cellular fibronectin independent of the R-G-D-S-containing site. By contrast, YadA failed to mediate binding to plasma fibronectin immobilized on nitrocellulose or plastic surfaces. These observations provide evidence for the hypothesis that the binding region for YadA in cellular fibronectin is not present in plasma fibronectin. This study is the first report on differential binding of bacteria to splicing variants of fibronectin. Further experiments might answer the question whether binding of YadA to cellular fibronectin contributes to the pathogenesis of yersiniae, both to the initial adhesion of the bacteria to the matrices of the host and to the arthritogenic potential of enteropathogenic yersiniae. PMID- 8500888 TI - Effect of abrogation of natural killer cell activity on the course of candidiasis induced by intraperitoneal administration and gastrointestinal candidiasis in mice with severe combined immunodeficiency. AB - Candida albicans CFU per gram of tissue recovered from livers, spleens, and kidneys of 12 severe combined immunodeficiency (scid) and 12 BALB/c mice 5 days after intraperitoneal (i.p.) administration of 10(7) C. albicans cells were not significantly different. Nine scid mice given normal rabbit serum (NRS) as a control and eight scid mice given anti-asialo-GM1 (alpha-ASGM1) had C. albicans CFU per gram recovered from livers and spleens 1 week after i.p. administration of C. albicans that were not significantly different, despite virtual elimination of natural killer (NK) cell activity in mice treated with alpha-ASGM1. At 2 weeks after i.p. administration, despite significantly increased NK cell activity in eight infected NRS-treated scid mice and virtual elimination of NK cell activity by alpha-ASGM1 treatment of eight scid mice, C. albicans CFU per gram recovered from livers and kidneys were not significantly different. At 2 weeks after intragastric administration of 2 x 10(6) C. albicans cells, eight NRS- and eight alpha-ASGM1-treated scid mice had identical proportions colonized with C. albicans and similar C. albicans CFU per gram recovered from feces. There was no evidence of hematogenous dissemination in either group. Similar results were seen 1 week after intragastric administration of 10(7) C. albicans cells. We conclude that NK cell activity is increased by i.p. administration of C. albicans in scid mice, but nontheless, abrogation of NK cell activity is not associated with enhanced susceptibility to candidiasis induced by i.p. administration and also is not associated with enhanced susceptibility to gastrointestinal colonization or hematogenous dissemination after intragastric administration of C. albicans. PMID- 8500889 TI - Facilitation of complement-dependent killing of the Lyme disease spirochete, Borrelia burgdorferi, by specific immunoglobulin G Fab antibody fragments. AB - In the absence of specific antibody, Borrelia burgdorferi is resistant to the bactericidal action of complement, despite the capacity of the spirochete to activate complement. Complement-mediated killing of B. burgdorferi requires the presence of antiborrelial immunoglobulin G (IgG). The effect of bactericidal IgG takes place after formation of the C5 convertase. Therefore, we examined the ability of Fab fragments from bactericidal IgG to mediate killing of B. burgdorferi by complement. The complement-activating domain of IgG, the Fc fragment, was not required for killing of borreliae, as monovalent Fab fragments prepared from immune IgG were also able to mediate killing. However, the killing efficiency of the Fab fragments was less than that of intact IgG, suggesting that the bactericidal activity of IgG is enhanced by divalency. IgG Fab-mediated killing occurred without increased complement activation or C3 fluid-phase consumption. Cell killing proceeded via the classical complement pathway, as no killing of Fab fragment-sensitized cells was observed in human serum deficient in C2. These results demonstrate directly that the bactericidal effect of anti-B. burgdorferi IgG is independent of the complement-activating properties of the antibody. PMID- 8500890 TI - Effects of Listeria monocytogenes and Yersinia enterocolitica on cytokine gene expression and release from human polymorphonuclear granulocytes and epithelial (HEp-2) cells. AB - The gene expression and cytokine release of the proinflammatory cytokines interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) after infection of human epithelial cells (HEp-2 cells) and polymorphonuclear granulocytes (PMNs) were investigated by using isogenic pairs of Listeria monocytogenes and Yersinia enterocolitica strains. By polymerase chain reaction assisted mRNA amplification and RNA dot blot analysis, we showed that PMNs and HEp-2 cells expressed enhanced levels of mRNA encoding IL-1 beta, IL-6, and TNF alpha after bacterial infection. Concomitant with the enhanced mRNA level, an increased secretion rate of IL-1 beta, IL-6, and TNF-alpha from PMNs as assessed by enzyme-linked immunosorbent assay was observed. HEp-2 cells after infection also released IL-6 and TNF-alpha into the cell supernatant, while no IL-1 beta release was detected. Cellular coincubation experiments were carried out with Transwell chambers. Our studies revealed that the coculture of PMNs and HEp-2 cells led to an increased IL-1 beta and IL-6 release. In contrast, after infection with the invasive bacteria, reduced levels of TNF-alpha were measured. Our data show that PMNs secrete the proinflammatory cytokines IL-1 beta, IL-6, and TNF-alpha within some hours after infection with L. monocytogenes and Y. enterocolitica and that cellular interactions with epithelial cells alone via soluble mediators influence the net amount of released proinflammatory cytokines. PMID- 8500891 TI - OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection. AB - C3H mice were actively immunized with outer surface protein A (OspA) at different intervals after infection with Borrelia burgdorferi to determine the effect of postexposure vaccination on the course of murine Lyme borreliosis. Mice were vaccinated with an OspA-glutathione transferase fusion protein or glutathione transferase (control) in complete Freund's adjuvant; vaccination was followed by two weekly booster injections in incomplete adjuvant. Two weeks after the final booster injection, organs were cultured for B. burgdorferi (blood, spleen, skin, and bladder) and examined for histopathology (joints and hearts). When vaccination was commenced in the early stages (5 to 14 days) of infection, active immunization with OspA partially cleared spirochetes from the bloodstream but did not eliminate them from other tissues or alter the course of joint or heart disease. Commencement of vaccination at 60 days after infection (at which time joint or heart disease is resolving), however, reduced both the number of mice and individual joints with arthritis, a result suggesting an acceleration of the resolution phase of the disease. Postexposure immunization with OspA may partially alter the course of murine Lyme arthritis but does not eliminate infection. PMID- 8500892 TI - Specific antibody to Haemophilus somnus in the bovine uterus following intramuscular immunization. AB - Sources of anti-Haemophilus somnus antibody in bovine uterine secretions following intramuscular immunization and subsequent intrauterine inoculation of killed H. somnus were investigated. Holstein cattle (n = 21) were immunized with a 270-kDa outer membrane protein from H. somnus (omp-270) by intramuscular injection. At estrus, the cattle were given an intrauterine inoculum of a heat killed suspension of a homologous strain of H. somnus containing omp-270 (n = 7), a heterologous strain of H. somnus lacking omp-270 (n = 7), or phosphate-buffered saline (n = 7). Uterine secretions were sampled by saline lavage immediately prior to inoculation and at 6, 24, 48, 72, 96, and 120 h after inoculation. Immunoglobulin G subclass I (IgG1) and IgG2 antibody specific for omp-270 were detectable in estrous uterine secretions of all systemically immunized cattle from which an adequate sample was obtained. IgM antibody specific for omp-270 was detected in serum following immunization but was not consistently detected in the uterine secretions of any animal. IgA antibody specific for omp-270 was not detectable in either serum or uterine secretions following immunization or intrauterine inoculation. Ratios of antibody to immunoglobulin and ratios of immunoglobulin to albumin in serum and uterine secretions indicated that about half the IgG1 and essentially all the IgG2 in secretions originated in the serum. Relative titers of IgG1 and IgG2 omp-270-specific antibodies in the uterine lumen and serum gave no evidence for selective transport of either subclass from serum into local secretions. Neither heterologous nor homologous intrauterine inocula detectably altered the serum contribution to antibody in uterine secretions within the sampling period. On the basis of these results, development of a systemic IgG2 antibody response may provide the basis for local immunological protection in the bovine reproductive tract. PMID- 8500893 TI - Expression of catalytically active recombinant Helicobacter pylori urease at wild type levels in Escherichia coli. AB - The genes encoding Helicobacter pylori urease, a nickel metalloenzyme, have been cloned and expressed in Escherichia coli. Enzymatic activity, however, has been very weak compared with that in clinical isolates of H. pylori. Conditions under which near wild-type urease activity was achieved were developed. E. coli. SE5000 containing recombinant H. pylori urease genes was grown in minimal medium containing no amino acids, NiCl2 was added to 0.75 microM, and structural genes ureA and ureB (pHP902) were overexpressed in trans to the complete urease gene cluster (pHP808). Under these conditions, E. coli SE5000 pHP808/pHP902) expressed a urease activity up to 87 mumol of urea per min per mg of protein (87 U/mg of protein), a level approaching that of wild-type H. pylori UMAB41 (100 U/mg of protein), from which the genes were cloned. Poor catalytic activity of recombinant clones grown in Luria broth or M9 medium containing 0.5% Casamino Acids was due to chelation of nickel ions by medium components, particularly histidine and cysteine. In cultures containing these amino acids, 63Ni2+ was prevented from being transported into cells and was not incorporated into urease protein. As a consequence, M9 minimal medium cultures containing histidine or cysteine produced only 0.05 and 0.9%, respectively, of active urease produced by control cultures containing no amino acids. We conclude that recombinant H. pylori urease is optimally expressed when Ni2+ transport is not inhibited and when sufficient synthesis of urease subunits UreA and UreB is provided. PMID- 8500894 TI - Proteus mirabilis urease: histidine 320 of UreC is essential for urea hydrolysis and nickel ion binding within the native enzyme. AB - Proteus mirabilis urease, a nickel-containing enzyme, has been established as a critical virulence determinant in urinary tract infection. An amino acid sequence (residues 308 to 327: TVDEHLDMLMVCHHLDPSIP) within the large urease subunit, UreC, is highly conserved for every urease examined thus far and has been suggested to reside within the enzyme active site. Histidine residues have been postulated to play a role in catalysis by coordinating Ni2+ ions. To test this hypothesis, oligonucleotide-directed mutagenesis was used to change amino acid His-320 to Leu-320 within UreC. The base change (CAT for His-320 to CTT for Leu 320) was confirmed by DNA sequencing. The recombinant and mutant proteins were expressed at similar levels in Escherichia coli as detected by Western blotting (immunoblotting) of denaturing and nondenaturing gels. Specific activities of the enzymes were quantitated after partial purification. Strains expressing the mutant enzyme showed no detectable activity, whereas strains expressing the recombinant enzyme hydrolyzed urea at 149 mumol of NH3 per min per mg of protein. In addition, the mutant enzyme was able to incorporate only about one-half (58%) of the amount of 63Ni2+ incorporated by the active recombinant enzyme. While the mutation of His-320 to Leu-320 within UreC does not affect expression or assembly of urease polypeptide subunits UreA, UreB, and UreC His-320 of UreC is required for urea hydrolysis and proper incorporation of Ni2+ into apoenzyme. PMID- 8500895 TI - Evidence that mannans of Candida albicans are responsible for adherence of yeast forms to spleen and lymph node tissue. AB - We have described a unique binding system between Candida albicans yeast-form cells and the marginal zone of mouse spleen (16). The chemical nature of the fungal adhesin(s) involved in this binding phenomenon was examined. A fraction obtained by 2-mercaptoethanol extraction (2-ME extract) of fungal cells caused a dose-response inhibition of yeast cell adherence to splenic marginal zone sites and also to subcapsular and medullary sinuses of mouse popliteal lymph nodes. Latex beads coated with the 2-ME extract showed a pattern of spleen and lymph node tissue binding identical to that observed with yeast cells. The extracted adhesins retained their binding activity in vivo. When 0.5 mg of the 2-ME extract was given intravenously to mice, spleen tissue removed up to 3 h later showed over 80% inhibition of yeast cell binding to the spleen marginal zone, and over 50% inhibition was retained for at least 24 h. The adhesins bound to a concanavalin A affinity column and were eluted by 0.5 M alpha-methyl-D mannopyranoside, and the eluted adhesins were designated Fr.II. Fr.II was further fractioned by DEAE-Sephacel ion-exchange column chromatography, and one especially active and abundant fraction was designated Fr.IIa. The adhesin moiety appeared to be carbohydrate, because the activity of Fr.IIa was destroyed by 20 mM sodium periodate or by 5 U of alpha-mannosidase, but boiling (30 min) or proteinase K (100 micrograms/ml) treatments had no effect. Chemically, whereas the 2-ME extract contained significant amounts of protein and mannose, Fr.IIa consisted of over 98% mannose and less than 0.5% protein. These data strongly suggest that the mannan portion within a mannoprotein is responsible for the binding of yeast cells to splenic marginal zone and to subcapsular and medullary sinuses of mouse lymph node tissue. PMID- 8500896 TI - Experimental Yersinia enterocolitica infection in euthymic and T-cell-deficient athymic nude C57BL/6 mice: comparison of time course, histomorphology, and immune response. AB - To elucidate the role of T lymphocytes in primary infection with Yersinia enterocolitica, we investigated the elimination rate of this pathogen, the histomorphology of tissue lesions, and the immune responses of athymic T-cell deficient C57BL/6 nude mice and their euthymic littermates after parenteral infection with Y. enterocolitica of serotype O:8. While a low inoculum of 3 x 10(2) Y. enterocolitica cells (about 0.01 times the median lethal dose for normal C57BL/6 mice) was cleared by normal C57BL/6 mice within 7 to 10 days, athymic nude C57BL/6 mice developed progressive infections after this inoculum, leading to death on days 20 to 25 postinfection (p.i.). While normal C57BL/6 mice experienced short-term transient infections, nude mice exhibited a biphasic, progressive infectious process. Thus, in the early phase (days 1 to 7 p.i.), a rapid influx of CD11b/18-positive cells (Mac-1 antigen) and natural killer cells was evident in the spleens and livers of the nude mice. The late phase (from day 8 p.i. onward) was characterized by a rapid progression of the infection and a further influx of CD11b/18-positive cells into the liver accompanied by an increase in bacterial counts and development of tissue lesions particularly in the liver and spleen. In normal mice, granuloma-like lesions composed of CD11b/18 , CD4-, and CD8-positive cells could be observed. However, granulomata were not found in nude mice. Yersinia-specific immunoglobulin G antibodies appeared on day 15 p.i. in the sera of normal mice, while nude mice failed to develop significant antibody titers. Adoptive transfer of Yersinia-specific T cells into athymic nude mice mediated resistance to Y. enterocolitica infection and restored both the ability of granuloma formation and the production of specific antibodies. In summary, the data presented herein strongly suggest that T lymphocytes play an essential role in the defense of C57BL/6 mice against Y. enterocolitica. PMID- 8500897 TI - Release of stress proteins from Mesocestoides corti is a brefeldin A-inhibitable process: evidence for active export of stress proteins. AB - Substantial evidence indicates that molecules released by infectious organisms affect virulence and influence immunity to infection. The characterization of extracellular molecules and their mechanism of release is therefore critical to understanding host-parasite relationships. The cestode parasite Mesocestoides corti is known to release at the larval stage several molecules including the heat shock proteins hsp70 and hsp60. In this report, it is shown that several molecules released by M. corti, including 70- and 60-kDa proteins, are induced by a temperature shift from room temperature to 37 degrees C. Such a shift is comparable to the thermal stress of parasites transmitted from insect vector to vertebrate host. By drug inhibition studies and Western blot (immunoblot) analyses, it is shown that M. corti hsp70 and hsp60 as well as other released molecules are actively exported. The active release of stress proteins by parasites has not been described and may play a critical role in the disease process. PMID- 8500898 TI - Sequence analysis of scrA and scrB from Streptococcus sobrinus 6715. AB - The complete nucleotide sequences of Streptococcus sobrinus 6715 scrA and scrB, which encode sucrose-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system and sucrose-6-phosphate hydrolase, respectively, have been determined. These two genes were transcribed divergently, and the initiation codons of the two open reading frames were 192 bp apart. The transcriptional initiation sites were determined by primer extension analysis, and the putative promoter regions of these two genes overlapped partially. The gene encoding enzyme IIScr, scrA, contained 1,896 nucleotides, and the molecular mass of the predicted protein was 66,529 Da. The hydropathy plot of the predicted amino acid sequence indicated that enzyme IIScr was a relatively hydrophobic protein. The gene encoding sucrose-6-phosphate hydrolase, scrB, contained 1,437 nucleotides. The molecular mass of the predicted protein was 54,501 Da, and the encoded enzyme was hydrophilic. The predicted amino acid sequences of the two open reading frames exhibited approximately 45 and 70% identity with those encoded by scrA and scrB, respectively, from Streptococcus mutans GS5. Homology also was observed between the N-terminal region of the S. sobrinus 6715 enzyme IIScr and other enzyme IIs specific for the glucopyranoside molecule, all of which generate glucopyranoside-6-phosphate during translocation and phosphorylation of the respective substrates. The sequence of the C-terminal domain of the S. sobrinus 6715 enzyme IIScr shared significant homology with enzyme IIIGlc from Escherichia coli and Salmonella typhimurium and with the C-terminal domain of enzyme IIBgl from E. coli, indicating that the two functional domains, enzyme IIScr and enzyme IIIScr, were covalently linked as a single polypeptide in S. sobrinus 6715. The deduced amino acid sequence of the gene product of S. sobrinus scrB shared strong homology with sucrase from Bacillus subtilis, Klebsiella pneumoniae, and Vibrio alginolyticus, suggesting conservation based on the physiological roles of these proteins. PMID- 8500899 TI - Variability of osp genes and gene products among species of Lyme disease spirochetes. AB - A comparison of the osp operon in 24 Lyme disease isolates, including representatives from each of the three established species, Borrelia burgdorferi, Borrelia garinii, and group VS461, was conducted. Several properties were assessed to determine whether the variability observed in this operon was reflective of the species of the isolate. At the transcriptional level, start site and Northern (RNA) blot analyses were conducted. B. garinii and VS461 group isolates were found to possess an untranslated leader sequence 6 nucleotides longer than that observed in B. burgdorferi isolates. By Northern blot analyses all Lyme disease isolates, except the B. garinii isolate VS102, were found to produce a polycistronic full-length ospAB message. Isolate VS102 produced a truncated message lacking the ospB portion of the transcript. Southern blot analyses suggest that the deletion occurred at the DNA level and was not due to a posttranscriptional event. Analysis of the outer surface proteins by two dimensional gel electrophoresis demonstrated that the OspB isoelectric points were variable, with the OspB of B. garinii isolates exhibiting a pronounced acidic shift. The reactivity of different isolates to OspA and -B monoclonal antibodies and to a hyperimmune anti-ospAB serum was also variable. The results presented here demonstrate genotypic and phenotypic heterogeneity in the osp operon at both the inter- and intraspecies levels. The results have implications concerning the use of the osp genes or their gene products in the development of a Lyme disease vaccine, as diagnostic markers of Lyme disease, and in subtyping of Lyme disease isolates. PMID- 8500900 TI - The cellular source of interleukin-6 during Listeria infection. AB - The cellular source of interleukin-6 (IL-6) during infection of mice with Listeria monocytogenes was investigated both in vitro and in vivo. Peritoneal cells taken at intervals from infected mice and cultured in vitro without added stimulus produced high titers of IL-6 peaking 2 days postinfection in a time course similar to that observed in vivo. Adherent cells with the morphology of macrophages were a major source of this IL-6. Spleen cells similarly harvested at intervals and cultured with heat-killed Listeria or heat-killed Brucella organisms as specific and nonspecific stimuli, respectively, showed two distinct IL-6 responses: (i) an early-phase response up to 5 days after infection when IL 6 production was elicited by either a specific or nonspecific stimulus, and when depletion of T cells had no effect, and (ii) a later response 7 to 10 days after infection when very high levels of IL-6 were produced in response to a specific stimulus. This response was lost when T cells were depleted in vitro or in vivo or in spleen cell cultures from mice with severe combined immunodeficiency. However, studies in vivo failed to show an important role for T cells governing serum IL-6. We conclude that most of IL-6 detected in vivo is produced by nonlymphocytes. Whether IL-6 produced by T lymphocytes in local foci of infection has any role in resolution of that infection is unknown. PMID- 8500901 TI - Helicobacter mustelae and Helicobacter pylori bind to common lipid receptors in vitro. AB - Helicobacter pylori is a recently recognized human pathogen causing chronic active gastritis in association with duodenal ulcers and gastric cancer. Helicobacter mustelae is a closely related bacterium with similar biochemical and morphologic characteristics. H. mustelae infection of antral and fundic mucosa in adult ferrets causes chronic gastritis. An essential virulence property of both Helicobacter species is bacterial adhesion to mucosal surfaces. The aim of this study was to determine whether H. mustelae binds to the same lipids shown previously to be receptors for H. pylori adhesion in vitro. By using thin-layer chromatography overlay and a receptor-based enzyme-linked immunosorbent assay, H. mustelae was found to bind the same receptor lipids as H. pylori, namely, phosphatidylethanolamine and gangliotetraosylceramide. In addition, both H. pylori and H. mustelae bound to a deacylplasmalogen phosphatidylethanolamine. In contrast to H. pylori, H. mustelae binding to receptors was unaffected by motility or viability. Murine monoclonal and bovine polyclonal antibodies against exoenzyme S, and exoenzyme S itself (from Pseudomonas aeruginosa), inhibited binding of H. mustelae to phosphatidylethanolamine and gangliotetraosylceramide. These findings show that H. mustelae binds in vitro to the same lipid receptors as H. pylori and suggest that the adhesion of H. mustelae to such species is mediated by preformed, surface-exposed adhesins which include an exoenzyme S-like protein. PMID- 8500902 TI - Immune responses and resistance to Toxoplasma gondii in mice immunized with antigens of the parasite incorporated into immunostimulating complexes. AB - Immunostimulating complexes were prepared with antigens extracted from tachyzoites of Toxoplasma gondii and were used to immunize mice. The major antigens incorporated into the immunostimulating complexes were the P30 and P22 antigens and an antigen with an approximate molecular weight of 6,000. Other antigens of molecular weights above 30,000 were also present. High antibody titers to T. gondii antigens and a delayed-type hypersensitivity reaction were noted for the immunized mice. Challenge of these mice with tachyzoites injected interperitoneally or with oocysts administered orally resulted in a statistically significant (P < 0.001) conditional probability of survival compared with that of controls. In contrast, the differences between immunized mice and controls challenged with tissue cysts did not attain statistical significance. PMID- 8500903 TI - Human submandibular-sublingual saliva promotes adhesion of Candida albicans to polymethylmethacrylate. AB - The purpose of this study was to identify components of saliva that interact with Candida albicans in solution and that may modulate adhesion to dental acrylic (polymethylmethacrylate [PMMA]) surfaces. Saliva-derived pellicles extracted from C. albicans blastoconidia and hyphal-form cells mixed with fresh human submandibular-sublingual saliva (HSMSL) contained predominantly high- and low molecular-weight mucins (MG1 and MG2, respectively). In contrast, few components from fresh human parotid saliva were adsorbed to yeast cells. Coating PMMA beads with HSMSL significantly enhanced (10-fold) adhesion of both growth forms of C. albicans compared with human parotid saliva (2-fold), suggesting a role for mucins in adhesion. HSMSL-enhanced adhesion was completely abolished by preadsorbing HSMSL with either blastoconidia or hyphal-form cells prior to coating PMMA. However, coating PMMA with purified salivary mucins or the addition of mucin to preadsorbed saliva did not enhance or restore adhesion to levels found with fresh HSMSL. Adhesion assays employing guanidine-treated fresh HSMSL showed a complete lack of Candida binding, suggesting that subjecting HSMSL to dissociating conditions may alter a property of salivary mucins crucial for C. albicans adhesion. Protease and glycosidase treatment of yeast cells significantly reduced adhesion to HSMSL-coated PMMA. In addition, preincubation of C. albicans with mannose and galactose inhibited adhesion to HSMSL-coated PMMA. These results suggest that mucins may play a role in C. albicans adhesion to saliva-coated PMMA and that a glycoprotein on the yeast surface may be involved in these events. PMID- 8500904 TI - Immunogenicity of overlapping synthetic peptides covering the entire sequence of Haemophilus influenzae type b outer membrane protein P2. AB - Haemophilus influenzae type b is a major cause of bacterial meningitis in young children. Antibodies against the outer membrane protein P2 are protective in the infant rat model of bacteremia. To identify conserved, surface-exposed, and protective epitopes of P2, 17 overlapping peptides covering the entire sequence of the protein were synthesized. Antisera from mice, guinea pigs, and rabbits raised against chromatographically purified P2 were tested for their reactivities to the peptides by enzyme-linked immunosorbent assays (ELISA). Three major linear immunodominant B-cell epitopes were mapped to residues 53 to 81, 241 to 265, and 314 to 341 of mature P2. Human convalescent-phase antisera also reacted strongly with these three epitopes. Rabbit antisera against all peptide-keyhole limpet hemocyanin conjugates except two peptides containing residues 8 to 19 and 302 to 319 recognized the corresponding peptides in ELISA and reacted with P2 on immunoblots. Immunization with all unconjugated peptides, except the 19 N terminal residues, induced very strong peptide-specific antibody responses, and these antisera reacted with P2 on immunoblots. Rabbit antisera raised against peptides corresponding to residues 1 to 14, 125 to 150, 193 to 219, and 241 to 319 also recognized P2 purified from H. influenzae nontypeable isolates. Identification of these immunodominant B-cell epitopes and conserved regions is a first step toward the rational design of a universal H. influenzae vaccine. PMID- 8500905 TI - Isolation of avirulent clones of Candida albicans with reduced ability to recognize the CR2 ligand C3d. AB - Four clones of the yeast Candida albicans, isolated on the basis of their tolerance to clotrimazole, were compared with their parental strains in terms of growth, morphology, virulence, and cell surface complement receptor activity. In a newly described synthetic medium, these clones, designated C1, C2, N, and P, produced germ tubes or pseudohyphae, but no true hyphae, in a pattern which was specific for each strain. The growth of each clone at 37 degrees C, under conditions which favor the filamentous growth form of the organism, was equal to that of the parental strain (H12). The pathogenicity of each clone was tested in an intravenous mouse model. None of the mice infected with the tolerant clones but all of the mice infected with H12 developed severe renal candidiasis after infection with 1.4 x 10(6) to 2.0 x 10(6) CFU/ml. The number of CFU of each clone from the mouse kidney was reduced about 3 or 4 orders of magnitude in comparison with the wild type. As a correlate, we measured the complement receptor activity (CR2 and CR3) of each clone. The C3 ligands, iC3b and C3d, were conjugated to sheep erythrocytes (E) sensitized with antibody (A) to the erythrocytes (EA). We found that all tolerant clones showed reduced recognition of C3d-bearing sheep erythrocytes (EAC3d) in rosetting assays. Clone P showed more than an 80% reduction in rosetting of EAC3d in comparison with H12 cells. In contrast, recognition of iC3b (EAiC3b) by each of the clones was similar to that by H12 cells. When dithiothreitol extracts of clone P and H12 were compared by immunoblot, both quantitative and qualitative differences in reactivities were observed with antibodies specific for the Candida C3d receptor and with antiserum from a patient with chronic mucocutaneous candidiasis. PMID- 8500906 TI - Mechanisms of attachment of Mycoplasma arthritidis to host cells in vitro. AB - Although other investigators have reported that Mycoplasma arthritidis failed to attach to several types of mammalian cells in vitro, we showed that it attached well to rat synovial fibroblasts, lung cells, and skin cells but not to kidney cells, suggesting that receptor sites are unequally expressed or distributed among different rat tissues. M. arthritidis also attached poorly to canine kidney and to baby hamster kidney cells, although it did attach to human fetal lung and fetal amnion cells. Four M. arthritidis strains, two virulent and two avirulent, all attached equally well to rat lung cells. Attachment was inhibited by trypsinization, suggesting that the major adhesins are protein. Fab' fractions of rabbit antisera against four M. arthritidis strains partially inhibited adherence of both homologous and heterologous strains, although not to the same extent, indicating some degree of antigenic heterogeneity among their adhesins. A filter cloned variant of M. arthritidis 158p10p9, designated LC1, attached poorly compared with the parent strain. Missing from this variant were two proteins migrating within the 81- to 90-kDa range by polyacrylamide gel electrophoresis; in their place was a 24-kDa antigen that may be a truncated version of one of these proteins. A monoclonal antibody that partially inhibited attachment recognized all these peptides by Western immunoblotting. An additional attachment inhibiting monoclonal antibody recognized a 71-kDa antigen present in both low adherence and fully adherent populations. The low-adherence variant LC1 induced slightly but significantly less arthritis in Lewis rats than did a fully adherent clone. PMID- 8500907 TI - A bacterial protease perturbs the paracellular barrier function of transporting epithelial monolayers in culture. AB - Tight junctions between cells and adhesion to the substratum maintain the barrier function of epithelia throughout the body. Damage to the epithelial barrier by microbial products allows penetration of bacteria and promotion of infection. We studied the effects of Pseudomonas elastase (PE) on the barrier function of epithelia by using Madin-Darby canine kidney (MDCK) epithelial cells; these cells form tight junctions (zonula occludens [ZO]) in vitro. PE decreased electrical resistance across the monolayers in a concentration- and time-dependent manner. Immunostaining of selected proteins of the ZO and zonula adherens was used to explore the effects of PE on junctional proteins. PE-treated monolayers of MDCK cells had markedly decreased immunostaining of ZO-1, a protein of the ZO, but light microscopy of PE-treated cells revealed no obvious morphologic changes. A chromium release assay indicated that, even with marked changes in transmonolayer electrical resistance, the permeability defect was not due to membrane disruption. Fluorescence staining of F-actin indicated diminution of cellular microfilaments in PE-treated cells, but E cadherin (uvomorulin), a protein of the zonula adherens, was unaffected by the enzyme. Elastases from porcine pancreas and human leukocytes with similar enzymatic activity (6 U/ml) did not decrease transmonolayer electrical resistance or degrade ZO-1. These results suggest that PE disturbs the barrier function of epithelial monolayers, in part, by changing the cell architecture and altering at least one protein of the ZO. PMID- 8500909 TI - Iron acquisition by Helicobacter pylori: importance of human lactoferrin. AB - Helicobacter pylori is known to be an etiologic agent of gastritis and peptic ulcer disease in humans. However, the mechanism by which this organism acquires iron has not been studied. For this investigation, H. pylori was grown in iron restricted medium. Siderophore production was not detected by chemical assays, and the strains were unable to use enterochelin and pyochelin for growth in low iron media. Human lactoferrin supported full growth of the bacteria in media lacking other iron sources, but neither human transferrin, bovine lactoferrin, nor hen ovotransferrin served as a source for iron. Since lactoferrin was found in significant amounts in human stomach resections with superficial or atrophic gastritis, the iron acquisition system of H. pylori by the human lactoferrin receptor system may play a major role in the virulence of H. pylori infection. PMID- 8500908 TI - Influence of genes from the major histocompatibility complex on the antibody repertoire against culture filtrate antigens in mice infected with live Mycobacterium bovis BCG. AB - C57BL/10 and C57BL/6 mice (H-2b); B10 congenic mice with f, k, p, q, r, and s H-2 haplotypes; B10 mice with recombinant g2, o2, a, h2, h4, i5, and bq1 H-2 haplotypes; and B6 mice with major histocompatibility complex (MHC) mutant bm1 and bm13 (class I) and bm12 (class II) haplotypes were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and examined by Western immunoblot analysis for serum antibodies against BCG culture filtrate antigens, following a boost injection with live BCG or with BCG culture filtrate. Parental B10 and B6 mice reacted very intensely with three culture filtrate protein bands with estimated molecular masses of 37, 38, and 40 kDa. Response against the 40 kDa protein was stronger following a boost injection with live BCG than following a boost with culture filtrate. Sera from mice with f, p, i5, bm1, and bm13 haplotypes reacted strongly, with both the 37-38- and 40-kDa antigens, and sera from mice with q and bq1 haplotypes showed a somewhat weaker reaction. Sera from mice with r, s, and bm12 haplotypes reacted against the 37-38-kDa antigen but not against the 40-kDa antigen, and sera from mice with the h2 haplotype reacted only with the 40-kDa antigen but not with the 37-38-kDa antigen. Sera from mice with the k, g2, o2, a, and h4 haplotypes showed, at most, a very weak reaction with the 37-38- and 40-kDa antigens. These results demonstrate that MHC genes profoundly affect the antibody repertoire used against culture filtrate antigens in mice infected with live M. bovis BCG. In particular, as shown in mice with the recombinant H-2 haplotype and in class II mutant bm12 mice, the I-A heterodimer controls the recognition of the immunodominant 40-kDa antigen. By using crossed immunoelectrophoresis, this 40-kDa antigen was identified as antigen 88 according to the reference system of Closs et al. for BCG antigens. PMID- 8500910 TI - A siderophore production mutant of Bordetella bronchiseptica cannot use lactoferrin as an iron source. AB - Bordetella bronchiseptica secreted a hydroxamate siderophore when grown in Fe depleted medium. A Tn5lac insertion mutant of B. bronchiseptica, DBB22, did not produce this hydroxamate siderophore and was incapable of using lactoferrin as an Fe source. Our data suggest that B. bronchiseptica uses a siderophore for removal of Fe from lactoferrin and transferrin rather than relying upon a receptor for these host Fe-binding proteins. PMID- 8500911 TI - Expression of contact-dependent cytolytic activity by Mycobacterium tuberculosis and isolation of the genomic locus that encodes the activity. AB - We investigated the presence of cytolytic activity in the virulent H37Rv and attenuated H37Ra strains of Mycobacterium tuberculosis and in the vaccine strain Mycobacterium bovis BCG. The virulent strain H37Rv expressed > 3-fold more contact-dependent cytolytic activity than the attenuated strain H37Ra, and the vaccine strain M. bovis BCG did not produce cytolytic activity. We also isolated an approximately 3.2-kbp fragment of the M. tuberculosis H37Rv genome that was capable of inducing this contact-dependent hemolytic activity in a nonhemolytic strain of Escherichia coli. PMID- 8500912 TI - Kinetics of serum and ocular antibody responses in susceptible mice that received a secondary corneal infection with Pseudomonas aeruginosa. AB - When susceptible C57BL/6J mice were infected with Pseudomonas aeruginosa in one eye and then reinfected in the previously uninfected contralateral control eye either 4 or 8 weeks after the primary infection, approximately 20 to 30% of the mice receiving a 4-week reinfection regimen restored corneal clarity within 4 weeks, while almost all of the 8-week-reinfected mice restored corneal clarity within 3 to 6 days postinfection. However, the rate of bacterial clearance was the same in both sets of mice despite the presence of opsonophagocytic antibodies only in the 8-week-reinfected mice. As determined by enzyme-linked immunosorbent assay, immunoglobulin G was the major immunoglobulin in both serum and ocular tissue of both mouse sets, and the immunoglobulin G level was two- to fourfold higher after the 8-week secondary infection than in the 4-week-reinfected mice. PMID- 8500913 TI - Relationship between loss of pigmentation and deletion of the chromosomal iron regulated irp2 gene in Yersinia pestis: evidence for separate but related events. AB - The irp2 gene, coding for a 190-kDa iron-regulated protein (HMWP2), and the hemin storage locus (hms), which determines Yersinia pestis pigmentation, are each located on a large chromosomal fragment which carries virulence genes and deletes spontaneously. To determine whether the two loci are located on one unstable fragment or on two different excisable DNA segments, the pigmentation status and the presence of irp2 in 43 strains of Y. pestis isolated in various parts of the world were examined. Three different types were observed: Pgm+ Irp2+ (39.5%), Pgm Irp2- (44.2%), and Pgm- Irp2+ (16.3%). No Pgm+ Irp2- strain was found. These three types were also recovered in vitro from the parental strain Saigon 55-12-39 (Pgm+ Irp2+), but again, no Pgm+ Irp2- colony was observed. Pgm- Irp2- derivatives were obtained from a single Pgm- Irp2+ colony, indicating sequential loss of the two traits. The fact that the genomic SpeI restriction patterns obtained by pulsed-field gel electrophoresis were specific for each of the three variants suggested that distinct large-scale chromosomal rearrangements had occurred in the Pgm- Irp2+ and Pgm- Irp2- derivatives. The virulence of Pgm- Irp2+ bacteria in mice was ca. 10(7)-fold lower than that of the Pgm+ Irp2+ strains injected subcutaneously but was not significantly decreased when injected intravenously. In contrast, the Pgm- Irp2- microorganisms were markedly less pathogenic (10(6)-fold) than the Pgm+ Irp2+ strains injected intravenously and were 100 times less virulent than the Pgm- Irp2+ strains injected subcutaneously. PMID- 8500914 TI - Primary swine intestinal cells as a model for studying Campylobacter jejuni invasiveness. AB - Swine small-intestinal enterocytes were used to test the invasiveness of Campylobacter jejuni. The cells were removed from the small intestines of 6-h-old piglets by enzymatic digestion. Two clinical C. jejuni isolates invaded swine enterocytes at significantly higher frequencies than an Escherichia coli control strain. The recovered colonies of C. jejuni T13192 appeared to be highly mucoid and invaded tissue culture cells (INT 407) at higher frequency (0.14%) than the parental strain (0.003%). The data not only support the previous in vitro findings regarding the invasiveness of C. jejuni but also suggest that invasiveness of C. jejuni may be an in vivo virulence attribute. PMID- 8500915 TI - Purification and characterization of streptolysin O secreted by Streptococcus equisimilis (group C). AB - Streptolysin O (SLO) was purified from culture supernatants of group C streptococci. The final product was either the complete, native molecule (SLOn [pI, 6.0]) with the N-terminal sequence (Asp)-Ser-Asn-Lys-Gln-Asn-Thr-Ala-Asn-Thr Glu-Thr- or a large fragment (SLOf [pI, 7.3]) with the N-terminal sequence Ala Pro-Lys-Glu-Met-Pro-Leu-Glu-Ser-Ala-Glu-Lys-Glu-Glu-Lys-. PMID- 8500916 TI - Production of interleukin-6 by human and murine mononuclear leukocytes stimulated with Plasmodium antigens is enhanced by pentoxifylline, and tumor necrosis factor secretion is reduced. AB - When pentoxifylline was present during stimulation of human mononuclear leukocytes with Plasmodium falciparum exogenous antigens, an increase in interleukin-6 production was observed simultaneously with a reduction of tumor necrosis factor secretion. Similar results were obtained in murine macrophages stimulated with P. vinckei antigens. This indicates the independence of interleukin-6 and tumor necrosis factor secretion in response to malaria antigens. PMID- 8500917 TI - Controlled, double-blind, multicenter clinical trial of iron protein succinylate in the treatment of iron deficiency in children. AB - A total of 502 children up to the age of 14 years were treated for iron deficiency or overt anemia. ITF 282 was prescribed to 256 children, and a commercially available ferrous polystyrene sulphonate preparation to 246, in a randomized double-blind, double-dummy, ten-center trial. One oral vial of ITF 282 (60 mg iron) was administered once a day to children weighing up to 40 kg; and twice a day to children with body weight equal or superior to 40 kg. In the reference group, oral vials of polystyrene sulphonate (52.5 mg iron) were administered once a day to children weighing up to 40 kg, and twice a day to children weighing 40 kg or more. Treatments lasted 60 days. The treatments' efficacy and tolerability were evaluated taking into consideration: special hematology, symptomatology, safety hematology and hematochemistry, urinalysis. At the end of treatment, the trend was detected to the normalization of the main hematologic parameters in both groups (hemoglobin, hematocrit, ferritin, blood iron, transferrin saturation, MCHC). Although in the first month the reference treatment appears to provide somewhat faster results, significantly greater values of blood iron are observed at the end of the observation in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was, although not significant, in favor of ITF 282, with a failure rate of 18.0 vs 24.0%. The general tolerance, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 13 patients complained of 13 events (1 heartburn, 6 constipation, 6 abdominal pain) vs 48 events reported by 43 patients with the reference medication (1 heartburn, 2 epigastric pain, 14 constipation, 14 abdominal pain, 3 skin rash, 14 vomiting). These observations confirm that, although the most modern preparations of ferrous ions exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease (with the use of more "physiologic" preparations in which the iron is reversibly bound to a protein carrier) the prevalence and, tendentially, duration and intensity of such events without prejudice for the clinical efficacy. Therefore, the good clinical tolerability of ITF 282 effectively removed one of the main obstacles to the correct compliance with iron treatments (necessarily to be taken long-term), as reduced the risks of undesired events in a particularly susceptible population subgroup, such as children. PMID- 8500918 TI - Midazolam and flunitrazepam: pharmacokinetics and effects on night time respiration and body movements in the elderly. AB - In a double-blind crossover study, the pharmacokinetics and effects on night-time respiration and body movements of midazolam 7.5 mg, flunitrazepam 1 mg, and placebo were studied in 5 elderly insomniac patients with the static charge sensitive bed-method (SCSB). In a supine position, the gastrointestinal absorption rate of flunitrazepam (tmax 0.6 h) was faster than that of midazolam (tmax 0.95 h). The elimination phase half-life of midazolam was about twice as long as reported earlier in healthy adult volunteers, but ageing did not affect the elimination of flunitrazepam. The shape of the serum concentration-time curve of both benzodiazepine derivatives was quite similar. The sleep of these five insomniacs became more peaceful and the respiration more regular during midazolam and flunitrazepam, compared with placebo. Both benzodiazepines significantly decreased body movements and the cumulative movement time remained shorter throughout the night, compared with placebo. Total variability (VI) was clearly decreased with flurazepam, and a similar but not statistically significant tendency was seen with midazolam, compared with placebo. Accordingly, the proportion of quiet sleep (QS) increased (p = 0.014) and the proportion of active sleep (AS) decreased (p = 0.019) with both benzodiazepines, compared with placebo. This reflects the changed control of respiration by higher brain structures. No signs of increased respiratory resistance (i.e. ballistocardiographic respiratory amplitude variation BRV < 60%) were seen with either of the drugs or placebo. There were no differences in the subjects' own estimation of their sleep during medication with these drugs. Only the sleep onset latency was shorter with flunitrazepam compared with midazolam and placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500919 TI - The role of metabolites in a bioequivalence study 1: loxapine, 7-hydroxyloxapine and 8-hydroxyloxapine. AB - Loxapine is a drug which is used in the treatment of psychotic disorders. The drug is extensively biotransformed in humans to produce a variety of metabolites, some of which have pharmacological activity. Seven-hydroxyloxapine is 4-5 times more active than the parent drug, although its concentrations in plasma are relatively low. Eight-hydroxyloxapine, on the other hand, is inactive, but is present in higher concentrations in plasma than the parent drug. In the present randomized crossover study to evaluate the bioequivalence of two dosage forms containing loxapine, the parent drug and its 7-hydroxy and 8-hydroxy metabolites were monitored for up to 96 hours after the administration of the test or reference formulations. Estimates of average bioavailability (AUC- infinity, AUC0t and Cmax) were obtained by the difference of the least squares means of log test and log reference. A 90% confidence interval for the log difference was derived from the within-subject error. The test of bioequivalence requires the 90% confidence band so calculated to fall entirely within an imposed regulatory interval of 80-125%. The results showed the two formulations to be bioequivalent in terms of the log mean differences and 90% confidence bands calculated for all three analytes. In fact, the within-subject variabilities of the metabolites were relatively low, so that the 90% confidence intervals for ln AUC0 infinity, ln AUC0t and ln Cmax calculated for the metabolites, were narrower that those for the parent drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500920 TI - Variation of Cmax and Cmax/AUC in investigations of bioequivalence. AB - In order to enable the setting of regulatory criteria for the equivalence of absorption rates on a sound scientific basis, the variation of Cmax/AUC and Cmax was evaluated. Under most conditions, the variation of Cmax/AUC was 10-25% higher than that of AUC independently of the variability of the extent of absorption. By contrast, the variation of Cmax was 50-60% higher than that of AUC and was strongly dependent on the variability of the extent of absorption. Therefore, it is recommended that for establishing the equivalence of absorption rates, the 90% confidence limits for the percentage ratio of the Cmax/AUC values of two drug products should be (based on their logarithmic averages or medians) between 75 and 133%. Regulatory decisions based on Cmax, while not favored, should expect that the 90% confidence limits for the percentage ratio of the Cmax values of two drug products be (based on their logarithmic averages or medians) between 70 and 143%. These recommendations parallel and are contingent upon the internationally harmonized criterion for the equivalence of extents of absorption which requires that the 90% confidence limits for the percentage ratio of two AUC values (based on their logarithmic averages or medians) be between 80 and 125%. PMID- 8500921 TI - Effects of nocloprost (9 beta-chloro-16,16-dimethyl PG E2) on absorption and disposition of antipyrine and sulfamethazine in healthy volunteers. AB - Prostaglandins are known to interfere with drug metabolizing processes. Nocloprost (9 beta-chloro-16,16-dimethyl PG E2) is a promising new cytoprotective prostaglandin in clinical evaluation for the treatment of ulcer disease and prophylaxis of gastric lesions caused by NSAID. Pharmacokinetic interactions of 400 micrograms nocloprost with 15 mg/kg antipyrine and 500 mg sulfamethazine (all given p.o.) were studied with a controlled, single-blind crossover trial in 16 healthy male volunteers (age 22-25 years, body weight 63-94 kg, body height 175 187 cm) in order to measure potential interferences with oxidative and conjugative drug metabolism. All individuals were extensive metabolizers of debrisoquine, 9 were slow and 7 rapid acetylators of sulfamethazine. Antipyrine and its major metabolites were measured in serum respectively, urine with the HPLC-method, sulfamethazine and its acetylated metabolite with a colorimetric technique. Nocloprost premedication (30 min prior to the test drugs) did neither interfere significantly with the oxidative processes involved in the disposition of antipyrine nor with the N-acetylation of sulfamethazine. Higher metabolic and renal clearance values of sulfamethazine in slow acetylators were most likely the result of the affected drug absorption. Nocloprost significantly reduced absorption rates of antipyrine and sulfamethazine in the group of slow but not of rapid acetylators. The extent of bioavailability remained unchanged. This phenomenon was certainly caused by the effects of the cytoprotective prostaglandin on those gastrointestinal functions which are determinants of drug absorption. PMID- 8500922 TI - Cocaine: a neonatal perspective. AB - This paper focuses on cocaine misuse as it impacts on neonates born at Grady Memorial Hospital in Atlanta, Georgia. The majority of infants of cocaine-using mothers (ICAM) appear clinically normal and pass through the "normal nursery." However, the longer hospital stay for the smaller, sicker ICAMs means that many cocaine-exposed sick infants are in the hospital at any time. The misperceptions of the pregnant cocaine-misusing woman often cause the ICAM to be born prematurely. The prematurity then superimposes other potential threats on the infant. Further, the environmental chaos into which these mothers and infants return following discharge may also contribute to the difficulties seen among these children. Finally, there are unanswered questions that have to be confronted by the hospital staff. These include ethical questions related to the "costs" of care to the cocaine-exposed infant. PMID- 8500923 TI - Relations of coping effort, coping strategies, perceived stress, and cigarette smoking among adolescents. AB - Coping strategies may influence adolescent smoking behaviour because they provide alternative behavioral and cognitive outlets which facilitate or inhibit smoking, or because they are expressions of general coping effort to smoke or not smoke. The present investigation examined three possibilities regarding how coping strategies versus coping effort compare as predictors of adolescent smoking: (1) general coping effort to not smoke may be a better predictor of adolescent smoking behaviors than are specific coping strategies; (2) coping strategies may be relatively better predictors of smoking behaviors; or (3) these two constructs may be relatively better predictors of different parameters of smoking behavior. Analytic strategies included calculation of a series of multiple regression models, involving (a) 11 coping strategies previously studied in adolescent smoking research, (b) a new simple measure of coping effort to not smoke, and (c) perceived stress, as concurrent predictors of four smoking-related items. Of the 11 coping strategies, partying, relaxation, seeking spiritual guidance, and getting revenge were related to at least one of the four cigarette smoking items. Only coping effort was directly related to recent smoking behavior, whereas only the coping strategies were related to cumulative smoking. Both types of items predicted refusal self-efficacy and intention to smoke in the future. Apparently, these two types of items show unique as well as common predictive variance. These results suggest that coping strategies are related to cumulative smoking for reasons other than motivation to not smoke. PMID- 8500924 TI - Role reversals in families of substance misusers: a transgenerational phenomenon. AB - Fifty adult methadone maintained opiate misusers were seen with their spouse and/or family of origin in outpatient therapy as part of a Veterans Administration Research project supported by NIDA. Family treatment was offered in an attempt to improve and enhance family relationships/social supports and to aid in the decrease or cessation of drug use. In this study, 42 of the 50 patients had parents who were substance misusers. The subjects were evaluated by constructing a Three-Generational Family Tree to define and clarify the nature of problems across the generations. Success or failure was measured by the Addiction Severity Index (ASI) which assessed drug use, problems with family, health, social relationships, legal difficulties, and employment as well as psychiatric symptoms. A recurrent problem of the "absent father" was identified across both generations studied. Thirty of the 50 opiate misusing men had absent fathers (usually due to alcohol or other drug misuse) and 27 of these 30 became absent fathers (also usually due to substance misuse) when they had children of their own. The absence of a father produced major developmental problems seen in these families. Particularly important was the "Parentified Child," forced to prematurely assume adult responsibilities. This age inappropriate role assumption was common in both the patients and their children, and was seen as a contributor to the initiation of drug misuse. A structured clinical intervention is described using the three-generational family tree to bring out these relationship issues, followed by supportive family therapy to restructure wounded family relationships from the family of origin and to bring about appropriate role expectations in the marital families. The findings suggest an improvement in legal difficulties, drug use, and psychiatric symptoms. PMID- 8500925 TI - Recidivism in a cohort of juvenile detainees: a 3 1/2-year follow-up. AB - We report some results from a longitudinal study of juvenile detainees. In extending previous analyses, we sought to determine whether the youth's alcohol or other drug use and their emotional/psychological problems at entry into the detention center predicted subsequent arrests for new offenses during the 36 months and 42 months following their initial interviews. Statistically significant relationships were found between the youths' demographic characteristics (age, race, gender) and cocaine use at initial interview (as measured by urinalysis), and recidivism. The policy implications of these findings are discussed. PMID- 8500926 TI - The incidence of pathological gambling among Native Americans treated for alcohol dependence. AB - The prevalence rate of potential and pathological gambling was examined among Native American and Caucasian patients (n = 85) being treated for alcohol dependence. Previous studies with alcohol-dependent (mainly Caucasian) populations revealed 10-15% to have gambling problems. This study, the first to measure pathological gambling among a Native American population, utilized the South Oaks Gambling Screen and was administered in a group setting, between 1/91 and 4/91 on the alcohol treatment ward of the Ft. Meade Veterans Administration Hospital. Results showed that 22% of the Native Americans studied (compared to 7.3% Caucasian), scored in a range indicating a probable pathological gambling addiction. Furthermore, 41% of the Native Americans studied (compared to 21.3% Caucasian) admitted to some difficulty with gambling. Education and treatment is encouraged to help stem projected radical increases in pathological gambling and related problems among this cultural group as Native American gambling becomes widespread. PMID- 8500927 TI - High school pupils' attitude and experience with drugs in Holon, Israel. AB - Five hundred and eight high school pupils filled out questionnaires concerning their attitudes and experience in the use of drugs: 3.15% had used drugs at least once. The beginning age was 14.36 +/- 1.55. Boys consumed more than girls (68.75 vs 31.25%). Pupil's permissive attitudes were in significant correlation with the following: controversy with parents (p < .05); breaking rules (discipline and property) (p < .05); drug consumption (p < .001); and positive parents' and friends' attitude toward drugs (p < .003). According to the pupils, the three main motives for beginning to take drugs were curiosity, peer influence, and existence of personal difficulties and/or seeking pleasure. The pupils' knowledge in the topic of drugs came from TV (92.5%, newspapers and periodicals (77.5%), and school (75%). PMID- 8500928 TI - Osteochondral allografts for osteochondritis dissecans and osteonecrosis of the femoral condyles. AB - Osteochondral allografts were used in 11 patients with osteochondritis dissecans and 4 with osteonecrosis of the femoral condyles. The lesions were mainly in the medial condyle in 13 cases, and in the weightbearing area in 10. The grafts had a mean size of 6 cm2; 8 were kept in hypothermia at 4 degrees C for less than 24 h and 7 were stored at -80 degrees C with cryoprotection. After an average follow up of 3.2 years, only 2 patients needed a further operation, one for nonunion and the other for a fracture of the graft. The others had improved clinically and showed radiological union of the graft with preservation of the joint space. PMID- 8500929 TI - Quantitative analysis of revascularisation and new bone formation in experimental bone grafts. The use of an image input and processing system. AB - Revascularisation and new bone formation in bone grafts has been extensively studied by histological techniques, but the images obtained are very complex and consequently difficult to evaluate quantitatively. We report similar analyses in experimental bone grafts using newer computerised digital techniques. Fresh autografts and fresh and frozen allografts were used. The histological analogue images from them were input digitally into an image processor. The amount of revascularisation and new bone formation could then be quantified in the different grafts. This system has proved to be a useful method of evaluation which could be applied to the quantitative analysis of other histological images. PMID- 8500930 TI - The ultrastructure of articular cartilage of the chicken's knee joint. AB - The articular cartilage and synovial membrane of immature and mature chicken knee joints were studied by light, scanning and transmission microscopy. The findings differed from human articular cartilage and we conclude that the chicken knee joint is not suitable as a model for human joint degeneration. PMID- 8500931 TI - Long term follow up of haemophilic arthropathy treated by Au-198 radiation synovectomy. AB - Intra-articular injection of Au-198 (gold synoviorthesis) has been used in the treatment of repeated haemarthroses of the elbows, knees, or ankles in 64 haemophiliacs. These patients had continued to have joint haemorrhages despite appropriate, episodic, substitutive therapy over a period of more than six months. Follow-up for an average period of 14 years in one knee in 38 male haemophiliacs showed 8 good, 23 fair, and 7 poor results with regard to their joint scores. It is concluded that Au-198 is an effective agent for radiation synovectomy, particularly in the early stages of the disease with minimal radiographic changes. It appears to reduce the incidence of haemarthrosis and to slow the rate of evolution of radiographic changes. PMID- 8500932 TI - Posterior tibial nerve palsy after intramedullary nailing. AB - Three cases of posterior tibial nerve palsy following reamed intramedullary nailing of the tibia are presented. This is a rare complication causing considerable morbidity. The possible mechanisms of neural injury are reviewed and guidelines for prevention are outlined. PMID- 8500933 TI - Radial artery entrapment. A rare complication of posterior dislocation of the elbow. AB - Vascular injuries may occur as complications of elbow dislocation and usually involve the brachial artery. A case report is presented in which only the radial artery was compromised as a result of the dislocation. PMID- 8500934 TI - [Acetabulum without cement. Short-term results of a series of 112 threaded cups]. AB - Between January 1982 and December 1987 we used 112 threaded acetabular cups in 102 patients undergoing total hip replacement. The clinical and radiographic results of 107 implants are reported in this survey. Using the functional grading of the hip advocated by Merle d'Aubigne and Postel, 62% can be classified as excellent, very good or good. On x-ray only 35% of the cups show neither radiolucency at the bone-implant interface nor migration of the component. There is a statistically significant correlation between a radiolucency in 2 of the 3 areas at the bone-implant interface and the clinical result. The revision rate for failure of the cup is 11.6% (13 implants). The actuarial survival of the threaded cup decreased from 0.95 in the 1st year to 0.75 in the 5th year after implantation. Analysis of our failures and of published data suggest that the problem lies in the lack of primary bone integration. We describe our difficulties in assessing risk factors, in interpreting the radiographs and in the intraoperative determination of component instability. The disappointing short term results have prompted us to abandon the use of threaded cups. PMID- 8500935 TI - Anterior cervical fusion with the Caspar instrumentation system. AB - We reviewed 106 consecutive patients who had undergone anterior cervical fusion with the Caspar instrumentation system between 1984 and 1989. Preoperative diagnoses were cervical spondylosis in 73 patients, a traumatic lesion in 12, ossification of the posterior longitudinal ligament in 9, cervical disc herniation in 6, and tumour or miscellaneous lesions in 6. In the 106 patients, 56 had two levels fused and 27 had three levels fused. At an average duration of follow-up of 4 years and 7 months, nonunion occurred in 3 of the 83 patients with multiple level fusions. Screw loosening occurred in 8 of the 106 patients, but there was no oesophageal perforation. PMID- 8500936 TI - The results of surgical treatment of lumbar arachnoiditis. AB - Forty patients with lumbar arachnoiditis, following previous operations, were classified into 4 myelographic types. Most patients with type I images had herniated disc symptoms with unilateral leg pain and limited straight-leg raising. Patients with types II and III myelographic appearances had bilateral leg pain, absent ankle jerks, weakness, cramps and signs of diffuse sensory deficit; some also had neurogenic claudication and urinary sphincter dysfunction. All patients with type IV had dysesthesia. Twenty-three of the 40 patients underwent reoperation and those with types I and II had acceptable results, but poor results occurred in those with types III and IV myelograms. PMID- 8500937 TI - Spinal cord evoked potentials in cervical and thoracic myelopathy. AB - We have studied 70 patients who underwent surgical decompression with or without fusion for cervical and/or thoracic myelopathy to assess the value of spinal cord evoked potentials (SCEP). The 70 patients included 42 with cervical spondylotic myelopathy, 10 with ossification of the posterior longitudinal ligament of the cervical spine and 18 with thoracic ligamentous ossification. Abnormal SCEP occurred in 88% of the patients with cervical myelopathy. Early recovery in intra and postoperative SCEP was associated with a better result. The severity of myelopathy correlated significantly with an abnormal SCEP in thoracic myelopathy. SCEP may reflect the severity of disease, and early recovery of intraoperative SCEP may also predict neurological improvement. PMID- 8500938 TI - Giant cell tumour of bone. A surgical approach to grade III tumours. AB - Thirty-one patients with giant cell tumours of bone (BGCT) were treated at our hospital by a conservative approach between 1975 and 1988. 94% of the tumours were grade III (Campanacci) and the follow up was from 2 to 13 years. In the 20 patients who had a modified intralesional excision (curettage) with bone grafting and cement, 5 recurrences occurred. There was one soft tissue recurrence in the 11 patients who had marginal or wide excisions. All recurrences were in grade III lesions. We conclude that grade III BGCT can be treated by modified intralesional excision provided the articular surfaces and part of the metaphysis are intact. PMID- 8500939 TI - Examination and evaluation of surgical margins in bone tumours. Comparative pre- and postoperative CT and MR imaging. AB - An objective method of evaluating surgical margins and the extent of limb preserving surgery is described in a study of 10 malignant bone tumours. The resected specimen was imaged by computerised tomography and magnetic resonance, and the appearances compared with the preoperative images of the tumour. CT was better than MR for detecting bony changes, but MR was more satisfactory for showing the extraosseous and intramedullary outline of the tumour. These two methods should therefore be combined. Intralesional excision is an absolute indication; marginal excision a relative indication for reoperation. PMID- 8500940 TI - [Multiple perforation in cryogenically preserved bone allografts. Comparative histological and microradiographic study of perforated and non-perforated allograft in sheep]. AB - Incorporation of massive cortical bone allografts in the human is slow and remains incomplete. Late biopsies of implanted allografts or histological studies of explanted allografts always show the partial substitution of necrotic bone by new bone from the host. The aim of the present study was to evaluate the value of drilling the massive deep-frozen cortical allografts in order to induce osteogenesis. Thirteen sheep were operated on and a standard segment of the proximal ulna was removed and the gap filled either by an unperforated allograft or by a perforated one. Based on histological and microradiographic examination, a complete substitution of the perforated allografts was observed but in this model no statistically significant difference was observed between perforated and unperforated allografts. Further study is needed to assess the effect of the perforations. PMID- 8500941 TI - High noon for U.S. health care reform. AB - A growing popular movement besieges a health policy status quo near financial as well as moral bankruptcy. A single-payer, Canadian-style national health program would assure universal, egalitarian coverage; democratic, rather than corporate, control of key policy choices; financing based on ability to pay; and cost controls that spare needed care as well as health workers' standard of living. Despite a misinformation campaign (generously funded by insurance and pharmaceutical firms) that slanders the Canadian experience, most Americans favor a national health program. The public health community should fight for no less. PMID- 8500942 TI - Questions and answers about managed competition. AB - The Managed Competition strategy for health care financing reform would push most people into cut-rate versions of health maintenance organizations chosen for them by their employer and owned by an insurance company. Many of those who currently enjoy good coverage would be forced into bare bones plans, and would forfeit the right to choose their health care provider. There is little evidence that the rigidly multi-tiered system created by Managed Competition would be more efficient or less expensive than the current U.S. system, and administrative costs would likely rise. Promises to expand coverage for the uninsured are likely to fall by the wayside if cost containment fails, and no current Managed Competition proposals address long-term care. In rural areas including at least 30 percent of the U.S. population, price competition central to the Managed Competition strategy is untenable since a long hospital or other provider cannot compete with itself. Managed Competition would empower vertically integrated corporate health care insurer/providers and disempower patients and the clinical work force. PMID- 8500943 TI - The politics of reform: public health insurance in Canada. AB - The centerpiece of Canadian health policy is a system of public health insurance covering the cost of hospital and medical services for all Canadians. The author analyzes the historical development of this policy and critically assesses its structure and dynamics. He argues that health insurance was won by Canadian workers through protracted industrial and political struggle. At the same time, health insurance was accommodated to the existing structure of power and privilege within the health care delivery system, which precluded a significant shift in the distribution of health care consumption and perpetuated the "irrationality" of a system that treats health as a problem located in the sphere of personal consumption. PMID- 8500944 TI - More myths and misconceptions: a reply to comments on an article. AB - Two issues in the debate about the relative economic success of Canada's health care system require clarification. First, while the upward trends in the share of health expenditures in GNP and in real per capita health expenditures have been similar in Canada and the United States for the last 30 years, only the latter has increased at a significantly lower rate since the early 1970s. Second, the trends in health expenditures are similar in Canada and the United States. The author therefore speculates that an explanation for the similarity in health expenditure trends may transcend international borders. PMID- 8500945 TI - Bush's and Clinton's fat cats. AB - As the 1992 presidential race went into full swing, Republican and Democratic fundraisers were busy soliciting $100,000 donations from corporations, labor unions and wealthy individuals. This kind of money is supposedly illegal in presidential campaigns, but both parties have found a way to launder it: by channeling it through their state affiliates and calling it "soft money." Whatever its name, it is compromising the integrity of the system. PMID- 8500946 TI - The other drug lords. AB - To gain an understanding of how hard it will be to control skyrocketing health care costs in the United States, consider one small part of the health care system: the pharmaceutical industry. Every time Congress threatens to crack down on drug costs or reduce government support for the industry, the pharmaceutical firms crank out PAC contributions and deploy their lobbyists. The upshot: drug companies get to charge what they want while holding onto millions of dollars' worth of government giveaways, including tax breaks and generous patent protection. PMID- 8500947 TI - How the U.S. press covers the Canadian health care system. AB - The U.S. media dwell on what they perceive as the shortcomings of the Canadian health care system, and minimize the advantages of providing free medical care for all. Focusing on specialization and high-tech treatments as the most important measure of health care quality, the media overlook the importance of greater access to medical care in promoting health. At the same time, the U.S. media are reluctant to cite the higher infant mortality rates and lower life expectancy rates in the United States compared with Canada. PMID- 8500948 TI - The Work Environment Board and the limits of social democracy in Canada. AB - A Work Environment Board was established to deal with all workplace health and safety issues within the Potash Corporation of Saskatchewan from 1978 to 1982. The Board was an experiment, established because of the observed deficiencies of the mandatory joint occupational health and safety committees that were legislated by the province in 1972. The administrators of the occupational health and safety program observed the problems faced by workers on these committees. An experiment was therefore established in one of the province's crown corporations that would transform the joint committee into a Work Environment Board with wider powers to deal with work environment matters within the corporation. In addition, a Work Environment Fund was established to enable the worker members on the Board to do their own research and to get the information they wanted. The Work Environment Board was frustrated by the fact that corporate leaders were not prepared to extend worker rights on the health and safety committees within the respective mines. Rather, they viewed health and safety reforms as part of an overall strategy of quality of work life. The social democratic government was not prepared to extend worker rights and to threaten management prerogatives. Now that there are three New Democratic Party (social democratic) governments in Canada, it appears that these governments are prepared to initiate technical improvements, but not the extension of worker rights in work environment matters. PMID- 8500949 TI - Conflicting agendas, interests, and actors in disease prevention policy-making: business, labor, and the High Risk Act. AB - During 1985-1988, the U.S. Congress considered and nearly passed the controversial "High Risk Act." This article analyzes the case in terms of a class dialectic perspective that views contradictory class interests, the political economy context, intraclass divisions, and institutional biases favoring dominant class interests as important, underlying factors in shaping the character, course, and outcome of the policy-making process. These concepts are used as the basis for explicating the political conflicts surrounding the legislation, the course of its consideration by the Congress, and its ultimate defeat. The sharp labor-business conflicts over the bills are shown to be closely tied to the legislation's potential effects upon their class-based economic and ideological/political interests. The course of Congressional consideration of the legislation is demonstrated as strongly influenced by contextual factors and intraclass divisions, especially those within the business community. Finally, indirect and direct institutional biases favoring business interests are shown to be particularly relevant to the legislation's defeat. In conclusion, the author develops a series of lessons regarding the disease prevention policy-making process which illustrate how the political dynamics and outcomes associated with episodes of occupational health policy reform may be interpreted through a class dialectic perspective focusing upon class interests, divisions, and struggle. PMID- 8500950 TI - Thinking and rethinking AIDS: implications for health policy. AB - In the United States, we see three main phases in the construction of the history of AIDS, with each having very different implications for health and social policy. In the first, AIDS was conceived of as an epidemic disease, a "gay plague," by analogy to the sudden, devastating epidemics of the past. In the second, it was normalized as a chronic disease, similar in many ways to diseases such as cancer. In the third, the authors propose a new historical model of a slow-moving, long-lasting pandemic, a chronic infectious ailment manifested through myriad specific HIV-related diseases. The new paradigm of AIDS incorporates the positive aspects of both earlier conceptions. It emphasizes, like the plague model, the etiology, transmission, and prevention of disease but rejects its assumption of a time-limited crisis. It takes from the chronic disease model an appropriate time frame and concern with the clinical management of protracted illness but insists on the primacy of prevention. The authors criticize both infectious and chronic disease models for their individualistic conceptions of disease and their narrow strategies for disease prevention. They further argue that the traditional distinction between, and approaches to, infectious and chronic diseases need to be rethought for other diseases as well as for AIDS. PMID- 8500951 TI - Changes in poverty, income inequality, and the standard of living in the United States during the Reagan years. AB - The record of economic well-being in the 1980s belied Reagan's claim that Americans would be better off if they scaled back the welfare state and cut tax rates. Though the standard of living rose, its growth was no faster than during 1950-1980. Income inequality increased. The rate of poverty at the end of Reagan's term was the same as in 1980. Cutbacks in income transfers during the Reagan years helped increase both poverty and inequality. Changes in tax policy helped increase inequality but reduced poverty. These policy shifts are not the only reasons for the lack of progress against poverty and the rise in inequality. Broad social and economic factors have been widening income differences and making it harder for families to stay out of poverty. Policy choices during the Reagan Administration reinforced those factors. PMID- 8500952 TI - The health status of women in the world-system. AB - The health status of women is examined within the context of a global political economy. The authors present a beginning attempt to model some key macrolevel processes linked to the health of women. In particular, a structural modeling technique known as LVPLS (or "soft modeling") is used to empirically test one recent formulation of world-system theory. The findings give added emphasis to the importance of the larger economic forces that affect women's health. PMID- 8500953 TI - How socioeconomic status affects birth and death rates in rural Kerala, India: results of a health study. AB - Data relating to birth and death were collected from throughout the state of Kerala, India, in a health survey conducted by the Kerala Sastra Sahitya Parishad, a voluntary organization. In this study, the authors analyze birth and death rates as calculated from the sample of 9,940 households (57,665 persons), with respect to other variables such as region, religion, and socioeconomic status. In order to study the effect of socioeconomic factors on birth and death rates, a socioeconomic status rating (SES rating) was developed, taking into account such factors as income, education, housing conditions, and land ownership. Socioeconomic status was found to have a definite influence on birth and death rates, with higher socioeconomic status resulting in lower birth and death rates. This effect was independent of such confounding variables as age structure of the population, religion, and region. The higher risk of mortality among the poorer households can partly be explained by the material deprivation: the higher birth rates could be the result of poorer educational attainments. PMID- 8500954 TI - Higher education for public health leadership. AB - The primary health care approach to public health stresses recognition of economic, political, and social determinants of health. In practice, briefly trained community health workers provide people with education and health care, but they require sound supervision. Such tasks of leadership require higher education. This demands more schools of public health of independent status, as well as stronger departments of community medicine within schools of medicine. Independent schools of public health throughout the world are much stronger than preventive medicine departments in medical schools, as measured by full-time faculty, scope of teaching and research, and candidates enrolled. To train properly for leadership, such independent schools in the developing world should be multiplied by 12 times to meet the needs. Leadership requires basic preparation in the full scope of public health knowledge, along with skills of effective management. PMID- 8500955 TI - We're number one! (Really?) Work and productivity. PMID- 8500956 TI - Dr. John Hamilton, 1943-1990. An appreciation. PMID- 8500957 TI - Special issue: Forensic treatment. PMID- 8500958 TI - Forensic psychiatric services in Britain: a current review. PMID- 8500959 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Treatment at Alabama's Taylor Hardin Secure Medical Facility. PMID- 8500960 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Massachusetts Treatment Center. PMID- 8500961 TI - Community-based forensic treatment of insanity acquittees. PMID- 8500962 TI - Mental health treatment services in Quebec for persons accused or convicted of criminal offences. PMID- 8500963 TI - Ontario's maximum security hospital at Penetanguishene: past, present, and future. PMID- 8500964 TI - Treatment and security: the dual nature of forensic psychiatry. PMID- 8500965 TI - Identity and development: the Dr. Henri van der Hoeven Kliniek in the nineties. PMID- 8500966 TI - Treatment of mentally ill offenders in Germany: with special reference to the newest forensic hospital--Straubing in Bavaria. PMID- 8500967 TI - Rhetoric and reality: what do we know about the English special hospitals? PMID- 8500968 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Introduction. PMID- 8500969 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Forensic treatment at Atascadero State Hospital. PMID- 8500970 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Treatment at Michigan's Forensic Center. PMID- 8500971 TI - Forensic treatment in the United States: a survey of selected forensic hospitals. Treatment services at Kirby Forensic Psychiatric Center. PMID- 8500972 TI - Perfusion in the anterior tibial muscle measured by laser Doppler flowmetry after graded periods of hindlimb ischemia in rats. AB - In the present study laser Doppler flowmetry was used to evaluate skeletal muscle perfusion before and after acute hindlimb ischemia in rats. Three laser Doppler microprobes were placed in the anterior tibial muscles of both legs. Six animals were used as non-ischemic controls and 22 animals were subjected to complete ischemia in the left hindlimb for 0.5 to 4.5 hr. By calculating a perfusion index based on recordings from the left and the right leg, a continuous measurement of relative perfusion could be performed. Reactive hyperemia was demonstrated after ischemia of shorter than 2 hr duration. After longer occlusion periods, the reperfusion decreased with increasing duration of ischemia. It is concluded that the use of laser Doppler microprobes offers possibility for continuous evaluation of relative microvascular blood flow in normal and postischemic skeletal muscle, and that the technique would be useful in experimental studies concerning ischemia-reperfusion injury of skeletal muscles. PMID- 8500973 TI - The effect of hypocapnia on skeletal muscle microcirculatory blood flow, oxygenation and pH. AB - Hypocapnia is known to decrease blood flow and tissue oxygen tension in the brain and the splanchnic organs, but there are few and contradictory results in skeletal muscle. The aim of the present study was to investigate the effect of hypocapnia on microcirculatory blood flow, local skeletal muscle PO2 (PtO2) and pH (pHt). Blood flow was measured using laser-Doppler flowmetry (LDF) and a multichannel antimony microelectrode served for PtO2 and pHt measurements. These parameters were studied in six anesthetized and mechanically ventilated rabbits during normocapnia (arterial PCO2 4.4 kPa), hypocapnia (PCO2 2.3 kPa) and finally a second period of normocapnia (PCO2 4.5 kPa). During normocapnia the relative LDF flux was 100 +/- 53% (mean +/- SD), decreased to 80 +/- 48% (p < 0.01) during hypocapnia and returned to 103 +/- 51% during the second period of normocapnia (N.S.). The PtO2 was 3.2 +/- 1.2 kPa, 2.9 +/- 0.8 kPa (p < 0.05) and 3.2 +/- 1.0 kPa (N.S.), respectively. pHt remained unchanged, although there was a significant arterial alkalosis (pH increased 0.10 units, p < 0.01). These results show that hypocapnia induces a 20% decrease in LDF flow and a 9% reduction in PtO2 with an unchanged pHt level. In this skeletal muscle model, the decrease in microcirculatory blood flow due to vasoconstriction leads to a reduction in both tissue oxygenation and in the removal of acid metabolites, which counteract a developing tissue alkalosis. PMID- 8500974 TI - Microvascular changes associated with high salt intake and hypertension in Dahl rats. AB - This study was undertaken to determine if an active reduction in small arteriole diameters or functional closure of these vessels contributes to increased vascular resistance in inbred hypertensive Dahl salt-sensitive (SS/Jr) rats. Fluorescence microscopy was used to study the spinotrapezius muscle arteriolar network in SS/Jr fed high (7%) or low (0.45%) salt diets for 4 weeks. Dahl salt resistant (SR/Jr) rats fed high or low salt diets were also studied to evaluate the exclusive effect of dietary salt on the microvasculature. High salt intake did not alter arterial pressure in SR/Jr, but caused marked hypertension (mean arterial pressure = 168 mm Hg) in SS/Jr. The diameter of large (arcade bridge) arterioles was significantly smaller in SS/Jr than SR/Jr, regardless of diet. The establishment of hypertension in SS/Jr was accompanied by an active diameter reduction in the intermediate (arcade) arterioles. However, there were no differences among groups in the density of perfused small arterioles or their diameters, and arteriolar density did not change with abolition of vascular tone in any group. In both strains, high salt intake reduced the passive diameter of large arterioles by 20%. Therefore, the establishment of hypertension in SS/Jr rats is associated with increased tone of proximal, but not distal, arterioles. In addition, distal arteriole rarefaction (functional or structural) does not contribute to increased spinotrapezius muscle resistance at this stage of salt induced hypertension. The salt-induced reduction in passive arteriolar diameters suggests that high salt intake alone can alter the structural and/or mechanical properties of the arteriolar wall. PMID- 8500975 TI - Two light attenuation models for automatic diameter measurement of the blood vessels. AB - The Lambert-Beer's law of the absorption of the light by blood in a vessel is used to model the light attenuation by a blood vessel that is transilluminated. Two models are used for an automatic vessel diameter determination for intravital microscopy. Some requirements for the photometric system have to be met in order to reduce errors due to light scattering. In these conditions, a videodensitometric pattern of the cross-section of the vessel can be fitted by the different models in order to obtain the diameter of the vessel. The first model proposed uses a uniformly distributed red blood cell column. A non-linear estimation of the diameter is done with the Levenberg-Marquardt method in 2 sec, using a regular PC386 microcomputer. The second one takes in account the presence of a plasma layer and computes the diameter of the red blood cell column and the diameter of the vessel in one minute. These models can be used for pharmacological studies or for a better understanding of the formation of a transilluminated intravital image. They can also be used for angiographic images. PMID- 8500976 TI - Laser Doppler flowmetry, transcutaneous oxygen pressure and thermal clearance in patients with vascular intermittent claudication. AB - In the present study, heat thermal clearance (HTC) was compared to laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (tcPO2), measured on the forefoot of 17 patients with vascular intermittent claudication and 10 controls in various positions at rest and after a treadmill exercise test. The mean ankle brachial systolic pressure ratio (ABSP) of the patients, measured using ultrasonic Doppler velocimetry, was 0.53 +/- 0.05. Their walking distance was 480 +/- 100 meters, the treadmill exercise being stopped as soon as pain sensation. No statistically significant difference was found between patients and controls for HTC, LDF, tc P02, forefoot and ankle skin temperatures. Statistically significant differences between patients and controls occurred in the sitting position for tcPO2, in standing position for HTC and after treadmill exercise for tcPO2 and LDF. When assuming the sitting position HTC did not vary significantly in patients and decreased in controls, LDF decreased and tcPO2 increased in both groups. After treadmill exercise, HTC in patients did not vary compared to supine values and HTC decreased in controls, tcPO2 remained unchanged in controls and decreased in patients, LDF increased in controls and decreased in patients. No significant correlations were found between the different techniques measured at rest in patients and controls. However in patients, after the treadmill test, LDF correlated with the walking distance (r = 0.667) and with ABSP (r = 0.641), HTC inversely correlated with the walking distance (r = -0.680) and ABSP (r = 0.577). Laser Doppler, tcPO2 and HTC are useful as tools to understand the alterations of cutaneous microcirculation of the lower limbs in patients with V.I.C.. However their results need to be interpreted with caution because these methods do not measure directly blood flow. PMID- 8500977 TI - A clinical comparison of two laser Doppler instruments. Fiber-optic probe versus integrated probe. AB - Two instruments for laser Doppler fluxmetry were compared; a diode laser (Diodopp) with a He-Ne gas laser (Periflux Pf1d). Spatial variability during baseline registration and temporal variability during 3 standardized provocation tests (suprasystolic occlusion, tilting and inspiratory gasp) were evaluated in 20 healthy volunteers. The coefficient of variation (= CV) of the registrations on four adjacent places did not show any significant difference between both instruments. The biological zero obtained during 5 minutes vascular occlusion was always zero with the Diodopp and 4 (3-5) (median, [minimum-maximum]) Perfusion Units with the Periflux. The hyperaemic response measured by both instruments was less pronounced during the Diodopp registration (percentage LDF increase 173% (15 350) vs 354% (86-1100), p < 0.001). Although the CV of the LDF parameters obtained by the Diodopp during the standardized provocation tests was almost always lower then with the Periflux, only occasionally the differences reached statistical significance. We concluded that both laser Doppler instruments are of equal value. The reproducibility of the Diodopp is slightly better, but the hyperaemic response after occlusion is registrated in a different way by both instruments. PMID- 8500978 TI - Skin capillary erythrocyte velocity and mean 24 hour ambulatory blood pressure level. AB - This study aimed to examine the relation between capillary dynamics and parameters of ambulatory blood pressure (BP) recordings in a range covering very low to high BP (mean arterial BP: 70-140 mm Hg). A total number of 45 subjects underwent a 24 h ambulatory BP recording at 30 min intervals. The subjects did not receive any medication. Then the subjects were subdivided in 5 categories along their mean 24 h arterial BP values < 80, 80-90, 91-105, 106-115, > 115 mm Hg. Nailfold capillaries were examined at the level of the fourth finger using TV microscopy. Our results demonstrate that erythrocyte velocity could be maintained relatively constant (mean velocities 700-800 microns/s) within the ambulatory mean arterial blood pressure range of 80-115 mm Hg. For very low and high blood pressures significant decreases (p < 0.01) were noted. Using office mean arterial blood pressure comparable results were obtained. PMID- 8500979 TI - NMR and the study of pathological state in cells and tissues. PMID- 8500980 TI - Aspects of amphibian metamorphosis: hormonal control. PMID- 8500981 TI - Biomineralization and eggshells: cell-mediated acellular compartments of mineralized extracellular matrix. PMID- 8500982 TI - Kinetics of alpha-dicarbonyls reduction by L-glycol dehydrogenase (NAD+) from Enterobacter aerogenes. AB - L-glycol dehydrogenase from Enterobacter aerogenes shows a high affinity by NADH (Ks = 2-4 microM; Km = 4.3-9.7 microM), which indicates that it must operate in vivo saturated with this coenzyme. Michaelis and dissociation constants for the reduction of the carbonyl substrates assayed (diacetyl, 2,3-pentanedione, methylglyoxal and ethyl pyruvate) are similar to those reported for other diacetyl reducing enzymes. The kinetic mechanism followed by these reactions has also been studied. Our results prove that the reduction of diacetyl and ethyl pyruvate takes place via an Ordered Bi-Bi system with the coenzyme as the leading substrate. Methylglyoxal and 2,3-pentanedione are reduced by the same mechanism or by a Theorell-Chance one. PMID- 8500983 TI - In vitro studies of natural killer cell activity in post traumatic stress disorder patients. Response to methionine-enkephalin challenge. AB - Attempts to define biological parameters that may be specifically associated with the pathophysiology of post traumatic stress disorder (PTSD) have met with only limited success, reflecting perhaps the practical limitations resulting from the high frequency of comorbidity of this condition with Axis I, II and III psychiatric diagnoses. We now report our studies on natural killer cell activity (NKCA), and the response of this cellular immune function to an in vitro methionine-enkephalin (MET) challenge in a population of Vietnam veterans with PTSD. Due to the characteristics of our PTSD patients, our protocol included four sex-matched, age-comparable control groups: (1) chronic alcoholics, (2) chronic drug abusers excluding alcohol, (3) chronic users of alcohol and other drugs of abuse and (4) drug-free, healthy volunteers. Although these groups did not significantly differ in their "baseline" NKCA, significant findings emerged from their response to preincubation with MET (10(-10), 10(-8) and 10(-6) M; 40:1 effector-to-target cell ratio). To minimize interindividual variations in the expression of NKCA each subject was used as its own control. Whereas peptide challenge resulted in an increase in NK lytic function in a subpopulation of group four (one or more MET concentrations, 8 out of 22 subjects), it produced mixed results in samples from individuals in group 2, and in general failed to elicit NKCA changes in the samples from participants in groups 1 and 3. Nine of the thirteen PTSD patients responded to MET preincubation with decreases in NKCA, which in five of them reached values below 20% of baseline for the three peptide concentrations tested. These findings may suggest that the "stress factor" in Vietnam veterans with PTSD plays a role in downmodulating NK lytic function in response to an in vitro MET challenge, an effect that appears to be potentiated by the use of drugs of abuse other than alcohol. The possible clinical relevance of these findings, including the identification of a subgroup of PTSD patients on the basis of immunological tests such as the one described in this work, deserves further investigation. PMID- 8500984 TI - Heterogeneity of splenic natural suppressor cells induced in mice by treatment with cyclophosphamide. AB - Administration of high dose cyclophosphamide (CY, 200 mg/kg body weight) to adult mice induces transient, nonspecific suppressor activity in the spleen of treated animals. Characterization of the CY-induced natural suppressor (NS) cells which inhibit mixed lymphocyte reactions revealed a heterogeneous population of lymphocytes expressing the CD8 T cell marker and the B220 B cell marker, as well as cells bearing the granulocyte-monocyte marker CD11b. On a cell per cell basis the most potent of these suppressors were found to be positive for CD11b. Inhibitory activity was also detected in the CD8-, CD11b-, B220- compartment of CY-spleen, suggesting the presence of null NS cells. The fact that several phenotypically distinct cell populations contribute to the overall inhibitory effect of CY-spleen cells indicates that natural suppression defines an activity rather than a specific cell type. Interestingly, NS activity was observed to reside solely within the fraction of CY-spleen that is agglutinable with soybean agglutinin or wheat germ agglutinin, suggesting that expression of receptors for these plant lectins is a universal characteristic of CY-induced NS cells, regardless of their lineage. CY-spleen cell-mediated suppression of lymphoproliferative responses was found to be partially dependent on DNA synthesis and totally dependent on protein synthesis, but did not require cell cell contact, indicating the production of soluble suppressor factor(s). PMID- 8500985 TI - Effects of inhibitors of arachidonic acid metabolism on serotonin release from rat basophilic leukemia cells. AB - Mast cells can release arachidonic acid (AA) metabolites as well as preformed mediators with IgE mediated stimulation, and these mediators are considered to play an important role in allergic reactions. The coincident release of preformed mediators and AA metabolites suggests that AA metabolism is related to mast cell degranulation. To clarify the relationship between mast cell degranulation and AA metabolism, the effects of various A cascade inhibitors on rat basophilic leukemia cell (RBL) mediator release induced by either anti-IgE or A23187 were examined. 5,8,11,14-eicosatetraynoic acid (ETYA) inhibited both PGD2 and LTC4/D4 generation, and partially inhibited serotonin release. Nordihydroguaiaretic acid (NDGA) caused complete inhibition of LTC4/D4 generation, and partial inhibition of PGD2 generation and serotonin release. The cyclooxygenase inhibitor, indomethacin, and the specific 5-lipoxygenase inhibitor, L-651,392 completely inhibited PGD2 and LTC4/D4 generation, respectively, without affecting release of other mediators. Both PGD2 and LTC4/D4 generation were abolished by the combination of indomethacin and L-651,392, however, serotonin release remained intact. HPLC analysis showed that no shift to other AA metabolites occurred after the treatment with these inhibitors. Mepacrine, a phospholipase A2 inhibitor, completely inhibited PGD2 and LTC4/D4 generation, as well as AA release itself, without affecting serotonin release. Therefore, neither AA metabolism nor AA release is necessary for RBL degranulation. PMID- 8500986 TI - Complement enhancement of HIV infection is mediated by complement receptors. PMID- 8500987 TI - Immunostimulatory potential of smokeless tobacco extract in in vitro cultures of murine lymphoid tissues. AB - Despite numerous studies on the general toxicologic effects of smokeless tobacco (ST) little immunotoxicologic information is available. As a first step in assessing the potential activity of ST on the immune system, the effects of an aqueous extract of ST was studied in in vitro cultures of mouse lymphoid cells. There was a significant increase in the proliferation of spleen cells cultured with different concentrations of ST extract. The polyclonal IgM antibody responses as determined by protein A plaque assay were also elevated in ST stimulated spleen cell cultures. Similar immunostimulatory results were seen in the mesenteric lymph node cell cultures also. ST extract was able to stimulate the spleen cells of the immune defective CBA/N mice. The mitogenic ability of ST extract may not be due to lipopolysaccharide (LPS) contamination as determined by its response in the LPS resistant C3H/HeJ mice spleen cells. ST extract was mitogenic not only to B cells but also to T cells. However the magnitude of response was less in T cells than in B cells. The proliferation of T cells was not accompanied by secretion of IL-2 or expression of IL-2 receptors on T cells. However there was an increase of IL-1 activity in spleen cells cultured with ST extract. Finally, activation of B or T lymphocytes by ST did not result in the elevation of intracellular calcium levels. Since ST is consumed orally, the chronic immunostimulation by ST in oral mucosal lymphoid tissues may be associated with the increased incidence of gingivitis, leukoplakia and oral cancer seen in human ST users. PMID- 8500988 TI - Tamoxifen: a caveat on the con side of the debate. PMID- 8500989 TI - Tamoxifen: a caveat on the pro side of the debate. PMID- 8500990 TI - Extraction of lipomas: a simple technique. AB - Benign lipomas are among the most common subcutaneous fatty tumors. They are often solitary, more common in women and occur frequently during the fourth and fifth decades. They usually involve the posterior neck, back and thighs, and the great majority are less than 2 cm in diameter. Malignant transformation is extremely rare, and they usually do not require treatment. However if removal is desired, surgical excision is curative. In this article we present a simple method of resecting large lipomas measuring 4 cm to 10 cm in diameter. PMID- 8500991 TI - Occurrence of members of the insulin superfamily in central nervous system and digestive tract of protochordates. AB - Antisera specific for mammalian insulin-like growth factor 1 (IGF-1) and mammalian insulin and the double immunofluorescence technique were used for this study. IGF-1-like-immunoreactivity was localized in entero-endocrine cells in the gastro-intestinal tract of the protochordates Ciona intestinalis and Branchiostoma lanceolatum. Some of the specimens also showed IGF-1-like immunoreactive (-IR) perikarya and fibers in the central nervous system. Whilst in rat endocrine pancreas, IGF-1-IR and insulin-IR occurred in different cell populations, in Ciona and Branchiostoma the vast majority of entero-endocrine cells and central neurons were IGF-1-like- +insulin-IR. A minor portion exhibited IGF-1-like-IR alone. For further characterization of the IGF-1-like-IR material, in Ciona intestinalis, peptides related to IGF-1 were identified by radioimmunoassay and gel chromatography. In accordance with the immunohistochemical results, IGF-I-like-IR was detected both in cerebral ganglion and in gastro-intestinal tract. Using acid gel chromatography, in Ciona gastro intestinal tract the IGF-1-like-IR was found to occur in two peaks, with apparent molecular weights of approximately 16 kDa and 3 kDa. Absorption studies with insulin- and IGF-related peptides, with crude extracts and the peak material obtained after gel chromatography, indicated that the IGF-1-like peptides in Ciona are different from mammalian insulin and IGF-1. The findings are in accordance with the presence of a common insulin/IGF precursor molecule in protochordates. PMID- 8500992 TI - In situ hybridization: mRNA levels of secretogranin II, VGF and peptidylglycine alpha-amidating monooxygenase in brain of salt-loaded rats. AB - The mRNA levels of secretogranin II (SgII), VGF and peptidylglycine alpha amidating monooxygenase (PAM) were studied in brains of salt loaded rats by in situ hybridization. In these rats the levels of the message for secretogranin II and VGF were increased in the paraventricular, supraoptic and retrochiasmatic nuclei and in the subfornical organ. The increases ranged from 416 to 721% for SgII and from 778 to 890% for VGF. The PAM message was also elevated in these brain regions; however, the maximal increase was only 221%. We conclude that the message for all secretory peptides investigated so far, i.e. vasopressin, galanin, secretogranin II and VGF are upregulated to a similar degree in the hypothalamus of salt-located rats. The relative increase in mRNA for the enzyme peptidylglycine alpha-amidating monooxygenase occurred to a much lower extent, and was comparable to the limited changes previously seen for carboxypeptidase H. PMID- 8500993 TI - The effects of three different demineralization agents on osteopontin localization in adult rat bone using immunohistochemistry. AB - Immunohistochemical localization of osteopontin, a phosphorylated acidic glycoprotein, was compared in adult rat femur fixed in 4% paraformaldehyde at 4 degrees C for 48 h and demineralized at 4 degrees C in ethylenediaminetetraacetic acid (EDTA), modified Jenkin's solution, or 15% formic acid, until radiographs indicated demineralization was complete. Formic acid was also evaluated at room temperature. EDTA solution (15 days) resulted in intense staining of osteocytes, periosteal osteoclasts and osteoblastic cells in osteonal bone. Osteoblasts were negative in the periosteum. No megakaryocyte staining was present; however, occasional neutrophils in the bone marrow were non-specifically stained. Demineralization in modified Jenkin's solution (16 days) showed osteopontin localization in bone matrix, hypertrophic and articular chondrocytes, and osteocytes. In cortical bone, almost all cement lines demarcating osteons showed very dense labeling. In the bone marrow, occasional megakaryocytes were immunopositive and neutrophils were non-specifically stained. Jenkin's produced non-specific staining of skeletal muscle and connective tissue. Formic acid demineralization (14 days, 4 degrees C) resulted in osteopontin expression in osteoblasts, osteocytes, osteoclast precursors, bone matrix, osteoid, cement lines, and chondrocytes; osteoclasts, although present in very low numbers, were also positive. More labeled osteoblasts could be identified compared to Jenkin's demineralization. Also more intense non-specific staining of the bone marrow neutrophils was obtained than with Jenkin's. Harsh, rapid demineralization with formic acid (4 days, room temperature) produced a loss in antigenicity demonstrated by a reduction in staining intensity not experienced with the 4 degrees C protocol; however, osteopontin was still localized in bone matrix and hypertrophic zone chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500994 TI - Predominant periportal expression of the phosphoenolpyruvate carboxykinase gene in liver of fed and fasted mice, hamsters and rats studied by in situ hybridization. AB - Zonal expression of phosphoenolpyruvate carboxykinase (PCK) mRNA in mouse, hamster and rat liver was studied by in situ hybridization with a radiolabelled rat antisense RNA probe. The abundance of PCK mRNA was determined by Northern blot analysis of total RNA with a digoxigenin-labelled probe. Livers were taken from animals that were sacrificed during the normal day/night cycle and after 29 h fasting. In situ hybridization revealed a heterogeneous distribution pattern of PCK mRNA in the liver of all three species throughout the whole day/night cycle. At the end of the dark period, i.e. at the end of feeding, with rats and mice but at a point of continuous feeding with hamsters, low amounts of PCK mRNA were restricted mainly to the periportal area. At the end of the light period, i.e. at the end of fasting with rats and mice but at a point of continuous feeding with hamsters, PCK mRNA levels were increased to a maximum and extended from the periportal to the intermediate zone. In mouse liver prolonged fasting caused a significant increase in PCK mRNA abundance with a nearly homogeneous distribution within the parenchyma. In hamster and rat liver, however, PCK mRNA levels slightly declined or remained constant, respectively, and the predominant localization of PCK mRNA in the periportal and intermediate zone was preserved. The present data suggest that the heterogeneous zonal activation of the PCK gene was essentially very similar in mouse, hamster and rat liver. PMID- 8500995 TI - Cytochemical characterization of basement membranes in the enamel organ of the rat incisor. AB - Ameloblasts are unique epithelial cells, in that once they have deposited the entire thickness of enamel and the process of maturation begins, they reform a basal lamina-like structure at their apical surface. In order to characterize further this basal lamina, its composition was analysed using (1) lectin-gold cytochemistry for glycoconjugates, (2) high-iron diamine (HID) staining for sulfated glycoconjugates and (3) immunogold labeling for collagen type IV and laminin. The labeling patterns were compared to that of other more "typical" basement membranes found in the enamel organ. Sections of rat incisor enamel organs embedded in Lowicryl K4M were stained with Helix pomatia agglutinin (HPA), Ricinus communis I agglutinin (RCA), wheat germ agglutinin (WGA) and Ulex europaeus I agglutinin (UEA). Samples from the late maturation stage were also reacted en bloc with lectins and embedded in Epon for transmission electron microscopic examination or prepared for scanning electron microscopy. Such samples were also stained with HID and conventionally processed for Epon embedding. Tissue sections were then reacted with thiocarbohydrazide-silver proteinate (TCH-SP). Analysis of the lectin labeling suggested that the region of extracellular matrix immediately adjacent to ameloblasts, where the basal lamina is situated, was intensely reactive with HPA and RCA, moderately reactive with WGA, and weakly reactive with UEA. In general, other basement membranes were mildly reactive with all lectins used. No HID-TCH-SP staining was observed directly over the basal lamina while numerous stain deposits were present over other basement membranes of the enamel organ. Immunolocalization of collagen type IV and laminin yielded a weak and variable labeling over the basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8500997 TI - Screening microbial metabolites for new drugs--theoretical and practical issues. PMID- 8500996 TI - Transient expression of a ventricular myosin heavy chain isoform in developing chicken intrafusal muscle fibers. AB - Sections of chicken tibialis anterior and extensor digitorium longus muscles were incubated with monoclonal antibodies against myosin heavy chains (MHC). Ventricular myosin was present in developing secondary intrafusal myotubes when they were first recognized at embryonic days (E) 13-14, and in developing extrafusal fibers prior to that date. The reaction in intrafusal fibers began to fade at E17, and in 2-week-old postnatal and older muscles the isoform was no longer recognized. Only those intrafusal fibers which also reacted with a monoclonal antibody against atrial and slow myosin contained ventricular MHC. Intrafusal myotubes which developed into fast fibers did not express the isoform. Hence, based on the presence or absence of ventricular MHC, two lineages of intrafusal fiber are evident early in development. Strong immunostaining for ventricular MHC was observed in primary extrafusal myotubes at E10, but the isoform was already downregulated at E14, when secondary intrafusal myotubes were still forming and expressed ventricular MHC. Only light to moderate and transient immunostaining was observed in coexisting secondary extrafusal myotubes, most of which developed into fast fibers. Thus at the time when nascent muscle spindles are first recognized, differences in MHC profiles already exist between prospective intrafusal and extrafusal fibers. If intrafusal fibers stem from a pool of primordial muscle cells, which is common to intrafusal and extrafusal myotubes, they diverged from it some time prior to E13. PMID- 8500998 TI - A novel class of platelet activating factor antagonists from Phoma sp. AB - Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation in vitro with an IC50 of 1.26 microM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs. PMID- 8500999 TI - Isolation and structure determination of novel phosphatidylinositol turnover inhibitors, piericidin B5 and B5 N-oxide, from Streptomyces sp. AB - In the course of a screening program for inhibitors of epidermal growth factor (EGF)-induced phosphatidylinositol turnover in human epidermoid carcinoma cell line A431, we discovered two novel compounds of the piericidin family from the culture broth and mycelia of a Streptomyces strain MJ288-OF3. We named them piericidin B5 and B5 N-oxide. By NMR and mass spectrometric analyses, the molecular formulas of piericidin B5 and B5 N-oxide were determined to be C27H41NO4 (MW 443) and C27H41NO5 (MW 459), respectively. Piericidin B5 and B5 N oxide inhibited phosphatidylinositol turnover of A431 cells with IC50S of 10.0 micrograms/ml and 1.1 micrograms/ml, respectively. PMID- 8501000 TI - Pradimicin S, a new pradimicin analog. I. Taxonomy, fermentation and biological activities. AB - A directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of HeLa-T4 cells expressing CD4 antigen and BSC-1 cells expressing gp-120 led to the isolation of pradimicin S, a new member of the pradimicin family. The producing strain (AA0851) was characterized as a new species of Actinomadura for which the name Actinomadura spinosa sp. nov. is proposed. Production of pradimicin S by strain AA0851 was significantly improved by addition of ferrous sulfate (0.1-0.4%) to the production medium. Pradimicin S showed potent activity against human immunodeficiency virus (HIV) LAVBRU strain in a CPE assay, and moderate activity against influenza virus type A. The antibiotic was active against a wide variety of fungi and yeasts in vitro and demonstrated in vivo efficacy against a systemic Candida albicans infection in mice. PMID- 8501001 TI - Pradimicins T1 and T2, new antifungal antibiotics produced by an actinomycete. I. Taxonomy, production, isolation, physico-chemical and biological properties. AB - Pradimicins T1 and T2, new members of the pradimicin family of antibiotics, were produced by an actinomycete strain AA3798. Pradimicin T1 exhibited potent activity against a wide spectrum of fungi in vitro and demonstrated efficacy against systemic Candida albicans and Aspergillus fumigatus infections in mice. PMID- 8501002 TI - Pradimicins T1 and T2, new antifungal antibiotics produced by an actinomycete. II. Structures and biosynthesis. AB - Pradimicins T1 and T2 are new members of the pradimicin family of antibiotics produced by an actinomycete strain AA3798. Pradimicins T1 and T2 are dihydrobenzo[a]naphthacenequinones substituted with 3 and 2 sugar moieties, respectively. The salient feature in their structures is an L-xylose attached to the phenolic hydroxyl group at C-11. Bioconversion experiments using a blocked mutant B-54 of strain AA3798 not only explored a plausible biosynthetic pathway of pradimicins T1 and T2, but also provided evidence of 5S,6S configuration. PMID- 8501003 TI - TAN-1057 A-D, new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus. Taxonomy, fermentation and biological activity. AB - Two Gram-negative bacteria were found to produce the new antibacterial antibiotics TAN-1057 A, B, C and D. The producing bacteria were characterized and designated as Flexibacter sp. PK-74 and PK-176. These antibiotics were active against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. TAN-1057 A inhibited protein biosynthesis in Escherichia coli and S. aureus. It showed excellent protective effects against an experimental methicillin-resistant S. aureus infection in mice. PMID- 8501004 TI - Incorporation of carbon-14 in the biosynthesis of the macrolide antibiotic, LL F28249-alpha. AB - A total of 76 mCi of 14C LL-F28249-alpha, nemadectin (1), having a specific activity of 35.2 microCi/mg was isolated from a fermentation using a mixture of approximately 600 mCi of 14C carboxyl labeled acetate, propionate and isobutyrate. Nemadectin was used to synthesize carbon-14 labeled moxidectin which is being developed as a highly efficient ectoparasitic anthelminth. The labeled positions were determined by 13C NMR analysis of 13C nemadectin which was obtained by similar incorporation of 13C carboxyl labeled acetate, propionate and isobutyrate. PMID- 8501005 TI - New virginiamycin M1 derivatives: synthesis, cholecystokinin binding inhibitory and antimicrobial properties. PMID- 8501006 TI - Synthesis and antifungal activity of pradimicin derivatives. Modifications of the sugar part. AB - Modifications at the sugar part of pradimicins were carried out by glycosidations of the aglycones or chemical transformations of natural pradimicins and their antifungal activity was evaluated. Among them, some of the D-xylose-modified derivatives (14, 17, 24) showed activity comparable to that of pradimicin A. The structure-activity relationships obtained through there studies clarified the role of the sugar part in the manifestation of antifungal activity: The 5-O-(6 deoxy-beta-D-sugar) is essential for activity and 2'-epi, 3'-oxo and 4'-deoxy sugar derivatives retain activity against yeasts. PMID- 8501007 TI - Chemical modification of erythromycins. IX. Selective methylation at the C-6 hydroxyl group of erythromycin A oxime derivatives and preparation of clarithromycin. AB - Although erythromycin A contains five hydroxyl groups, regioselective methylation at the C-6 hydroxyl group was achieved to the extent of 90% when a 9-O substituted erythromycin A 9-oxime was employed as substrate. The methylation and its selectivity are dependent on an O-protecting group at the 9-oxime, solvent, base, and methylating reagent. In particular, the use of a polar aprotic solvent is indispensable for the methylation. Among the 9-oxime derivatives, 2'-O,3'-N bis(benzyloxycarbonyl)-N-demethylerythromycin A 9-[O-(2-chlorobenzyl)oxime] was the most important intermediate for the synthesis of clarithromycin (6-O methylerythromycin A). PMID- 8501008 TI - Octapeptide derivatives of teicoplanin antibiotics. AB - A series of octapeptide derivatives of teicoplanin-A2 component 2 (CTA/2), its aglycone (TD), and the L-lysyl derivatives of an amide of CTA/2 and TD, were prepared by condensation of the terminal amino group with N-hydroxysuccinimidyl esters of tert-butyloxycarbonyl (BOC) L- and D-amino acids, followed by acidic (TFA) removal of the BOC protecting function. The antimicrobial properties of these compounds were compared with those of the corresponding unmodified antibiotics and their N15-acetyl derivatives. The most active derivatives were the octapeptides with N-terminal glycine or lysine whose in vitro activity was comparable to that of the parent teicoplanins. The glycinyl and lysyl derivatives of CTA/2 showed better activity than CTA/2 against clinical isolates of Staphylococcus epidermidis and S. haemolyticus for which teicoplanin MICs were relatively high. No significant difference in their antibacterial activity was observed between octapeptides containing L- or D-lysine. PMID- 8501009 TI - N63-carboxamides of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin and deglucoteicoplanin. AB - The synthesis and biological properties of a series of N63-carboxamides of 15-N alkylated derivatives of teicoplanin A2 (CTA) and its aglycone (TD) are described. Among the compounds, those carrying hydrophilic groups or ionizable amino functions on the N15-alkyl chain are more soluble in water than parent N15 methylated or unmodified amides. Selected compounds were more active in vitro than CTA or TD, and a few of them were also slightly more efficacious in vivo than the parent antibiotics in streptococcal septicemia in the mouse. Their degree of activity varied with the structure and length of the N15-alkyl chains. PMID- 8501010 TI - A new antibiotic, structurally related to leptomycin A, flattens the morphology of v-ras(ts) NRK cells. PMID- 8501011 TI - Aspochalasin E, a new antibiotic isolated from a fungus. PMID- 8501012 TI - Antibiotic AC6H, a new component of tetrocarcin group antibiotics. PMID- 8501013 TI - Beta-cyanoglutamic acid, a new antifungal amino acid from a streptomycete. PMID- 8501014 TI - BU-4704, a new member of the xanthocillin class. PMID- 8501015 TI - Competitive inhibition of squalene synthetase by squalestatin 1. PMID- 8501016 TI - Deacetylation effect of N,N-dimethylvancosamine in saptomycins D and E. PMID- 8501017 TI - Acid degradation studies of 6-deoxyerythromycin A. PMID- 8501018 TI - Respirantin, a novel insecticidal cyclodepsipeptide from Streptomyces. PMID- 8501019 TI - TTL auto flash in close-up photography. PMID- 8501020 TI - Disease prevention and the biomedical image. PMID- 8501021 TI - TTL auto flash--Part 2: The TTL auto system as a manual flash meter for close-up photography. PMID- 8501022 TI - Biological photographic collections: Truman Blocker, Jr. History of Medicine collections. PMID- 8501023 TI - Photographic enhancement of (PVDF) western blots using ultraviolet radiation. PMID- 8501024 TI - 100,000 slides later: a four-year history of producing computer-generated slides. PMID- 8501025 TI - TQM in the healthcare industry. PMID- 8501026 TI - Gel-cel lead-acid batteries for biophotographic applications. PMID- 8501027 TI - Artificial hearing. PMID- 8501028 TI - Adhere today, here tomorrow: oral bacterial adherence. PMID- 8501029 TI - Hydrolysis of urea by Ureaplasma urealyticum generates a transmembrane potential with resultant ATP synthesis. AB - When urea is added to Ureaplasma urealyticum, it is hydrolysed internally by a cytosolic urease. Under our measuring conditions, and at an external pH of 6.0, urea hydrolysis caused an ammonia chemical potential equivalent to almost 80 mV and, simultaneously, an increase in proton electrochemical potential (delta p) of about 24 mV with resultant de novo ATP synthesis. Inhibition of the urease with the potent inhibitor flurofamide abolished both the chemical potential and the increase of delta p such that ATP synthesis was reduced to approximately 5% of normally obtained levels. Uncouplers of electrochemical gradients had little or no effect on these systems. The electrochemical parameters and ATP synthesis were measured similarly at three other external pH values. Any change in delta p was primarily via membrane potential (delta psi), and the level of de novo ATP synthesis was related to the increase in delta p generated upon addition of urea and more closely to the ammonia chemical potential. Although the organisms lack an effective mechanism for internal pH homeostasis, they maintained a constant delta pH. The data reported are consistent with, and give evidence for, the direct involvement of a chemiosmotic mechanism in the generation of around 95% of the ATP by this organism. Furthermore, the data suggest that the ATP-generating system is coupled to urea hydrolysis by the cytosolic urease via an ammonia chemical potential. PMID- 8501030 TI - Dual response regulators (NarL and NarP) interact with dual sensors (NarX and NarQ) to control nitrate- and nitrite-regulated gene expression in Escherichia coli K-12. AB - Two sensor proteins, NarX and NarQ, mediate nitrate regulation of anaerobic respiratory gene expression. Either of these sensors is sufficient to signal the presence of nitrate to the response regulator protein, NarL, a transcriptional activator and repressor. Two observations suggested the existence of a second response regulator that is also involved in nitrate regulation. First, narL null mutants retain residual nitrate induction of fdnG operon expression; this residual induction is absent in narX narQ double-null strains. Second, nitrate induction of aeg-46.5 operon expression is substantially enhanced in narL null strains (M.H. Choe and W.S. Reznikoff, J. Bacteriol. 173:6139-6146, 1991). We found that this nitrate induction requires either the NarX or the NarQ protein, consistent with the existence of a second response regulator. We designate this second regulator NarP. We isolated insertion mutants that are defective in aeg 46.5 operon expression. These insertions are in the narP gene, which encodes a response regulator that is 44% identical to the NarL protein. Null alleles of narP abolished aeg-46.5 induction and also eliminated the residual NarL independent nitrate induction of fdnG operon expression. Both the NarX and NarQ proteins communicate with both the NarP and NarL proteins. We found that the primary signal for NarP-dependent aeg-46.5 operon induction is nitrite rather than nitrate. By contrast, nitrite is a relatively weak signal for NarL-dependent induction. In narX null strains, nitrate was an efficient signal for NarL dependent induction, and this induction required the NarQ protein. We conclude that, in wild-type strains, the NarQ protein communicates the presence of nitrite to both the NarP and NarL proteins and that the NarX protein inhibits this communication with the NarL protein. PMID- 8501031 TI - Cloning and genetic characterization of the Helicobacter pylori and Helicobacter mustelae flaB flagellin genes and construction of H. pylori flaA- and flaB negative mutants by electroporation-mediated allelic exchange. AB - Helicobacter pylori is one of the most common human pathogens. It causes chronic gastritis and is involved in the pathogenesis of gastroduodenal ulcer disease and possibly gastric carcinoma. Helicobacter mustelae is a bacterium closely related to H. pylori that causes gastritis and ulcer disease in ferrets and is therefore considered an important animal model of gastric Helicobacter infections. Motility, even in a viscous environment, is conferred to the bacteria by several sheathed flagella and is regarded as one of their principal virulence factors. The flagellar filament of H. pylori consists of two different flagellin species expressed in different amounts. The gene (flaA) encoding the major flagellin has recently been cloned and sequenced. Here we report the cloning and sequencing of two highly homologous new flagellin genes from H. pylori 85P and H. mustelae NCTC 12032. The nucleotide sequence of the H. pylori gene proved that it encoded the second flagellin molecule found in H. pylori flagellar filaments. The genes were named flaB. The H. mustelae and H. pylori flaB genes both coded for proteins with 514 amino acids and molecular masses of 54.0 and 53.9 kDa, respectively. The proteins shared 81.7% identical amino acids. The degree of conservation between H. pylori FlaB and the H. pylori FlaA major flagellin was much lower (58%). Both flaB genes were preceded by sigma 54-like promoter sequences. Mapping of the transcription start site for the H. pylori flaB gene by a primer extension experiment confirmed the functional activity of the sigma 54 promoter. To evaluate the importance of both genes for motility, flaA- and flaB-disrupted mutants of H. pylori N6 were constructed by electroporation-mediated allelic exchange and characterized by Western blot (immunoblot) analysis and motility testing. Both mutations selectively abolished the expression of the targeted gene without affecting the synthesis of the other flagellin molecule. Whereas flaA mutants were completely nonmotile, flaB mutants retained motility. PMID- 8501032 TI - Functional studies of yeast glucokinase. AB - Glucose phosphorylation capacity is known to be in excess of glucose flux in Saccharomyces cerevisiae wild type but not in a mutant strain lacking the two hexokinases but still having glucokinase. Nonetheless, we show here that in the latter strain, as in the wild type, the internal concentration of glucose is apparently low during growth on glucose and that additional glucokinase activity does not increase glucose flux. The glucokinase-dependent strain accumulates substantial amounts of glucose internally in batch culture after exhaustion of glucose, as well as from maltose. In both of these situations, low concentrations of radioactive glucose provided to the medium are used with incomplete, if any, mixing with the internal pool. Furthermore, in contrast to activity of hexokinase and other enzymes, little glucokinase activity is revealed by toluene treatment of cells. These results may point to a connection between glucose entry and its phosphorylation by glucokinase, but separate explanations for the various findings are also possible. PMID- 8501033 TI - Characterization of an iron-regulated promoter involved in desferrioxamine B synthesis in Streptomyces pilosus: repressor-binding site and homology to the diphtheria toxin gene promoter. AB - Desferrioxamine B is the main siderophore of Streptomyces pilosus. Its production is induced in response to iron limitation. Two genes involved in desferrioxamine production have been cloned and were found to be translated from a polycistronic mRNA that is produced only under conditions of iron limitation (T. Schupp, C. Toupet, and M. Divers, Gene 64:179-188, 1988). Here we report the nucleotide sequence of the desferrioxamine (des) operon promoter region. The transcriptional start site was localized by S1 nuclease mapping. Deletion analysis defined a 71 bp region downstream of the -35 region that is sufficient for iron regulation in the original host, S. pilosus, and also in Streptomyces lividans. Site-directed mutagenesis was used to create a mutation that abolishes iron repression. Two iron-independent mutants were obtained by deletion of part of a 19-bp region with dyad symmetry which overlaps the -10 promoter region and the transcriptional start site. The putative repressor-binding site identified by these constitutive mutations is not homologous to the consensus binding site of the Escherichia coli central iron repressor, Fur (ferric uptake regulation), but is similar to the DtxR-binding site in the iron-regulated promoter of the corynebacterial diphtheria toxin gene. PMID- 8501035 TI - Analysis of mutants of Salmonella typhimurium defective in the synthesis of the nucleotide loop of cobalamin. AB - The CobIII region of the cobalamin (CBL) biosynthetic (cob) operon of Salmonella typhimurium encodes functions necessary for the synthesis of the nucleotide loop of CBL and comprises three genes, designated cobU, cobS, and cobT (26). Complementation studies identified two classes of CobIII mutants: (i) 34 mutants were complemented by a plasmid carrying the cobU+ gene, and (ii) 27 mutants were complemented by a plasmid carrying the cobS+ gene; none of the mutants tested was complemented by the cobT+ clone, a result suggesting that no cobT mutations were isolated. These data were consistent with those of complementation studies done with F' cobUST plasmids, which also suggested that the CobIII region comprises two complementation groups. A plasmid carrying cobUS+ was sufficient to complement a deletion of the entire CobIII region, a result suggesting that CobT was not required for CBL biosynthesis. Nutritional studies done with synthetic putative intermediates of the CobIII pathway were performed to further classify cobIII mutants. A subset of cobU mutants were found to be responsive to exogenous dicyano-cobinamide-GDP, while cobS mutants were found to be responsive only to CBL. These results are consistent with the adenosyl-cobinamide kinase GTP:adenosyl-cobinamide-phosphate guanylyltransferase and CBL synthase activities proposed for CobU and CobS, respectively. The cobIII genes under the control of the T7 promoter were overexpressed, and the resulting polypeptides were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three polypeptides with apparent molecular masses of 22, 26 and 39 kDa, consistent with the predicted masses for CobU, CobS, and CobT, respectively, were detected. PMID- 8501034 TI - Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. AB - Salmonella typhimurium synthesizes cobalamin (vitamin B12) de novo under anaerobic conditions. Of the 30 cobalamin synthetic genes, 25 are clustered in one operon, cob, and are arranged in three groups, each group encoding enzymes for a biochemically distinct portion of the biosynthetic pathway. We have determined the DNA sequence for the promoter region and the proximal 17.1 kb of the cob operon. This sequence includes 20 translationally coupled genes that encode the enzymes involved in parts I and III of the cobalamin biosynthetic pathway. A comparison of these genes with the cobalamin synthetic genes from Pseudomonas denitrificans allows assignment of likely functions to 12 of the 20 sequenced Salmonella genes. Three additional Salmonella genes encode proteins likely to be involved in the transport of cobalt, a component of vitamin B12. However, not all Salmonella and Pseudomonas cobalamin synthetic genes have apparent homologs in the other species. These differences suggest that the cobalamin biosynthetic pathways differ between the two organisms. The evolution of these genes and their chromosomal positions is discussed. PMID- 8501036 TI - Signal sequence processing is required for the assembly of LamB trimers in the outer membrane of Escherichia coli. AB - Proteins destined for either the periplasm or the outer membrane of Escherichia coli are translocated from the cytoplasm by a common mechanism. It is generally assumed that outer membrane proteins, such as LamB (maltoporin or lambda receptor), which are rich in beta-structure, contain additional targeting information that directs proper membrane insertion. During transit to the outer membrane, these proteins may pass, in soluble form, through the periplasm or remain membrane associated and reach their final destination via sites of inner membrane-outer membrane contact (zones of adhesion). We report lamB mutations that slow signal sequence cleavage, delay release of the protein from the inner membrane, and interfere with maltoporin biogenesis. This result is most easily explained by proposing a soluble, periplasmic LamB assembly intermediate. Additionally, we found that such lamB mutations confer several novel phenotypes consistent with an abortive attempt by the cell to target these tethered LamB molecules. These phenotypes may allow isolation of mutants in which the process of outer membrane protein targeting is altered. PMID- 8501037 TI - A new putative sigma factor of Myxococcus xanthus. AB - A third putative sigma factor gene, sigC, has been isolated from Myxococcus xanthus by using the sigA gene (formerly rpoD of M. xanthus) as a probe. The nucleotide sequence of sigC has been determined, and an open reading frame of 295 residues (M(r) = 33,430) has been identified. The deduced amino acid sequence of sigC exhibits the features which are characteristic of other bacterial sigma factors. The characterization of a sigC-lacZ strain has demonstrated that sigC expression is induced immediately after cells enter into the developmental cycle and is dramatically reduced at the onset of sporulation. A deletion mutant of sigC grows normally in vegetative culture and is able to develop normally. However, in contrast to the wild-type cells, the sigC deletion mutant cells became capable of forming fruiting bodies and myxospores on semirich agar plates. This suggests that sigC may play a role in expression of genes involved in negatively regulating the initiation of fruiting body formation. PMID- 8501038 TI - Isolation and characterization of the ndhF gene of Synechococcus sp. strain PCC 7002 and initial characterization of an interposon mutant. AB - The ndhF gene of the unicellular marine cyanobacterium Synechococcus sp. strain PCC 7002 was cloned and characterized. NdhF is a subunit of the type 1, multisubunit NADH:plastoquinone oxidoreductase (NADH dehydrogenase). The nucleotide sequence of the gene predicts an extremely hydrophobic protein of 664 amino acids with a calculated mass of 72.9 kDa. The ndhF gene was shown to be single copy and transcribed into a monocistronic mRNA of 2,300 nucleotides. An ndhF null mutation was successfully constructed by interposon mutagenesis, demonstrating that NdhF is not required for cell viability under photoautotrophic growth conditions. The mutant strain exhibited a negligible rate of oxygen uptake in the dark, but its photosynthetic properties (oxygen evolution, chlorophyll/P700 ratio, and chlorophyll/P680 ratio) were generally similar to those of the wild type. Although the ndhF mutant strain grew as rapidly as the wild-type strain at high light intensity, the mutant grew more slowly than the wild type at lower light intensities and did not grow at all under photoheterotrophic conditions. The roles of the NADH:plastoquinone oxidoreductase in photosynthetic and respiratory electron transport are discussed. PMID- 8501039 TI - Nucleotide sequence of the celG gene of Clostridium thermocellum and characterization of its product, endoglucanase CelG. AB - The nucleotide sequence of the celG gene of Clostridium thermocellum, encoding endoglucanase CelG, was determined. The open reading frame extended over 1,698 bp and encoded a 566-amino-acid polypeptide (molecular weight of 63,128) similar to the C. thermocellum endoglucanase CelB (51.5% identical residues). The N terminus displayed a typical signal peptide, followed by a catalytic domain. The C terminus, which was separated from the catalytic domain by a 25-amino-acid segment rich in Pro, Thr, and Ser, contained two conserved stretches of 22 amino acids closely similar to those previously described in other cellulases from the same organism. Expression of the gene in Escherichia coli was increased by fusing the fragment coding for the catalytic domain in frame with the start of the lacZ' gene present in the vector. A low- and a high-M(r) form of the protein were purified. The two forms displayed identical enzymatic properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that both forms consist of a major polypeptide of M(r) 50,000 and two minor polypeptides of M(r)s 49,000 and 48,000, resulting from heterogeneous proteolytic cleavage at the C terminus. An antiserum raised against the forms purified from E. coli reacted with an immunoreactive polypeptide of M(r) 66,000, which was associated with the extracellular cellulolytic complex of C. thermocellum known as the cellulosome. PMID- 8501040 TI - Identification of genes encoding components of the swarmer cell flagellar motor and propeller and a sigma factor controlling differentiation of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus possesses two distinct motility systems, the polar system used for swimming in liquid environments and the lateral system used for swarming over surfaces. Growth on surfaces induces swarmer cell differentiation and expression of the lateral motility system. Mutants, created by transposon mutagenesis of a clone expressing lateral flagellin and gene disruption in V. parahaemolyticus, were unable to swarm and failed to make lateral flagellin; therefore, unlike the case for the polar system, there is one gene (lafA) encoding lateral flagellin. In addition to lafA, other genes required for swarming but not for swimming were identified by gene replacement mutagenesis. The nucleotide sequence of the clone determined open reading frames (ORFs) and deduced amino acid sequences showed similarities to flagellar components of other bacteria: flagellin, hook-associated protein (HAP2), motor components, and flagellar sigma factor (sigma 28). Many sigma 28 factors have been shown to recognize cognate promoters; however, expression of lafA in Escherichia coli required LafS, and E. coli sigma 28 did not substitute. Also, there were no sequences preceding genes encoding flagellin or HAP2 resembling the sigma 28 consensus promoter. The product of the sigma-like gene seems to be a unique member of the sigma 28 cluster. It appears the result of requiring expression for immunodetection of flagellin clones was that the sigma locus was fortuitously cloned, since the sigma and lafA loci were not contiguous in the chromosome. This work initiates identification and placement of genes in a scheme of control for swarmer cell differentiation; three levels have been identified in the transcriptional hierarchy. PMID- 8501041 TI - Reductive pentose phosphate-independent CO2 fixation in Rhodobacter sphaeroides and evidence that ribulose bisphosphate carboxylase/oxygenase activity serves to maintain the redox balance of the cell. AB - Whole-cell CO2 fixation and ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) activity were determined in Rhodobacter sphaeroides wild-type and mutant strains. There is no obvious difference in the levels of whole-cell CO2 fixation for the wild type, a form I RubisCO deletion mutant, and a form II RubisCO deletion mutant. No ribulose 1,5-bisphosphate-dependent CO2 fixation was detected in a form I-form II RubisCO double-deletion mutant (strain 16) or strain 16PHC, a derivative from strain 16 which was selected for the ability to grow photoheterotrophically with CO2 as an electron acceptor. However, significant levels of whole-cell CO2 fixation were detected in both strains 16 and 16PHC. Strain 16PHC exhibited CO2 fixation rates significantly higher than those of strain 16; the rates found for strain 16PHC were 30% of the level found in photoheterotrophically grown wild-type strain HR containing both form I and form II RubisCO and 10% of the level of the wild-type strain grown photolithoautotrophically. Strain 16PHC could not grow photolithoautotrophically in a CO2-H2 atmosphere; however, CO2 fixation catalyzed by photoheterotrophically grown strain 16PHC was repressed by addition of the alternate electron acceptor dimethyl sulfoxide. Dimethyl sulfoxide addition also influenced RubisCO activity under photolithoautotrophic conditions; 40 to 70% of the RubisCO activity was reduced without significantly influencing growth. Strain 16PHC and strain 16 contain nearly equivalent but low levels of pyruvate carboxylase, indicating that CO2 fixation enzymes other than pyruvate carboxylase contribute to the ability of strain 16PHC to grow with CO2 as an electron acceptor. PMID- 8501042 TI - Inhibition of expression of the tryptophanase operon in Escherichia coli by extrachromosomal copies of the tna leader region. AB - Expression of the tryptophanase (tna) operon in Escherichia coli is regulated by catabolite repression and transcription attenuation. Expression is induced by the presence of elevated levels of tryptophan in a growth medium devoid of a catabolite-repressing carbon source. Induction requires the translation of a 24 residue coding region, tnaC, located in the 319-nucleotide transcribed leader region preceding tnaA, the structural gene for tryptophanase. Multicopy plasmids carrying the tnaC leader region were found to inhibit induction of the chromosomal tna operon. Mutational studies established that this inhibition was not due to inhibited transcription initiation, translation initiation, tryptophan transport, or enzyme activity. Rather, multicopy tnaC plasmids inhibited induction by preventing tryptophan-induced transcription antitermination in the leader region of the tna operon. Translation of the single Trp codon in tnaC of the multicopy plasmids was shown to be essential for this inhibition. We hypothesize that translation of the Trp codon of the leader peptide titrates out a trans-acting factor that is essential for tryptophan-induced antitermination in the chromosomal tna operon. We postulate that this factor is an altered form of tRNATrp. PMID- 8501043 TI - Analysis of the periplasmic [NiFe] hydrogenase transcription unit from Desulfovibrio fructosovorans. AB - Two genes, hynA and hynB, encode the two subunits of the periplasmic [NiFe] hydrogenase in Desulfovibrio fructosovorans. Sequencing downstream from hynB revealed a third open reading frame (hynC) that has the potential for encoding a polypeptide showing 21% identity with the HyaD, HoxM, and HupD proteins, belonging to putative operons encoding Escherichia coli hydrogenase 1, Alcaligenes eutrophus H16 membrane-bound hydrogenase, and Rhizobium leguminosarum uptake hydrogenase, respectively. Northern (RNA) blotting with a structural gene probe revealed the existence of a major transcript of 2.9 kb, which is the appropriate length to contain the two hydrogenase subunits only. In addition, two minor 4.4- and 5.8-kb transcripts that could contain hynABC and additional genes were found. The 5' end of the most abundant [NiFe] hydrogenase mRNA was found 170 bp upstream from the translational start site of hynA. The sequences at -10 and 35 relative to the transcriptional starting site showed 55% homology with the consensus sequences of the Escherichia coli sigma 70-type promoter. The cloning of that particular region as a promoter to control transcription of the lacZ gene in E. coli DH5 alpha or the hynA, hynB, and hynC genes in D. fructosovorans MR400 led to strong expression in both systems. PMID- 8501044 TI - Sequence and molecular characterization of a DNA region encoding a small heat shock protein of Clostridium acetobutylicum. AB - A DNA region of Clostridium acetobutylicum containing a gene (hsp 18) with significant homology to a family of small eukaryotic heat shock proteins was cloned and sequenced. It is the second reported sequence of a low-molecular weight heat shock protein from gram-positive bacteria and is induced not only by heat shock but also at the onset of solventogenesis, as determined by Northern (RNA) blot analysis, thus confirming the results of an earlier study performed at the protein level (A. Pich, F. Narberhaus, and H. Bahl, Appl. Microbiol. Biotechnol. 33:697-704, 1990). By primer extension analysis, a transcriptional start site was identified 149 bp upstream of hsp18. This site was preceded by a region that exhibits high homology to the consensus promoter sequences of gram positive bacteria, as well as sigma 70-dependent Escherichia coli. A direct repeat structure was detected in the -35 region. The promoter is located 196 bp from the start of a potential regulatory tRNA(Thr)ACG gene involved in the shift to solventogenesis which is transcribed in the opposite direction. A putative rho independent transcription termination structure was identified at the 3' end of hsp18. PMID- 8501045 TI - The Escherichia coli K-12 "wild types" W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels. AB - The widely used and closely related Escherichia coli "wild types" W3110 and MG1655, as well as their common ancestor W1485, starve for pyrimidine in minimal medium because of a suboptimal content of orotate phosphoribosyltransferase, which is encoded by the pyrE gene. This conclusion was based on the findings that (i) the strains grew 10 to 15% more slowly in pyrimidine-free medium than in medium containing uracil; (ii) their levels of aspartate transcarbamylase were highly derepressed, as is characteristic for pyrimidine starvation conditions; and (iii) their levels of orotate phosphoribosyltransferase were low. After introduction of a plasmid carrying the rph-pyrE operon from strain HfrH, the growth rates were no longer stimulated by uracil and the levels of aspartate transcarbamylase were low and similar to the levels observed for other strains of E. coli K-12, E. coli B, and Salmonella typhimurium. To identify the mutation responsible for these phenotypes, the rph-pyrE operon of W3110 was cloned in pBR322 from Kohara bacteriophage lambda 2A6. DNA sequencing revealed that a GC base pair was missing near the end of the rph gene of W3110. This one-base-pair deletion results in a frame shift of translation over the last 15 codons and reduces the size of the rph gene product by 10 amino acid residues relative to the size of RNase PH of other E. coli strains, as confirmed by analysis of protein synthesis in minicells. The truncated protein lacks RNase PH activity, and the premature translation stop in the rph cistron explains the low levels of orotate phosphoribosyltransferase in W3110, since close coupling between transcription and translation is needed to support optimal levels of transcription past the intercistronic pyrE attenuator. PMID- 8501046 TI - In Azotobacter vinelandii hydrogenase, substitution of serine for the cysteine residues at positions 62, 65, 294, and 297 in the small (HoxK) subunit affects H2 oxidation [corrected]. AB - The essential role of the small (HoxK) subunit of hydrogenase of Azotobacter vinelandii in H2 oxidation was established. This was achieved by modification of the two Cys-X2-Cys amino acid motifs at the N and C termini of the HoxK subunit (Cys-62, -65, -294, and -297). The Cys codons were individually mutated to Ser codons. Modifications in these two motifs resulted in loss of hydrogenase activity. At the N terminus, the mutations of the codons for the motif Cys-62-Thr Cys-64-Cys-65 decreased the activity of hydrogenase to levels no higher than 30% of those of the parental strain. H2 oxidation with the alternate electron acceptors methylene blue and benzyl viologen was decreased. H2 evolution and exchange activities were also affected. Cys-64 possibly substitutes for either Cys-62 or Cys-65, allowing for partial activity. Mutation of the codons for Cys 294 and Cys-297 to Ser codons resulted in no hydrogenase activity. The results are consistent with alterations of the ligands of FeS clusters in the HoxK subunit of hydrogenase [corrected]. PMID- 8501047 TI - Physical map of the Streptomyces lividans 66 genome and comparison with that of the related strain Streptomyces coelicolor A3(2). AB - A physical map of the chromosome of Streptomyces lividans 66 ZX7 was constructed by ordering the macrorestriction fragments generated from the genomic DNA with the restriction enzymes AseI and DraI. AseI and DraI linking cosmids (i.e., recombinant cosmids including either AseI or DraI sites) were isolated from a gene bank and used as hybridization probes against Southern transfers of pulsed field gel electrophoresis (PFGE) restriction patterns. The DraI sites were precisely mapped by PFGE analyses of AseI-DraI double digests and hybridization with the AseI junctions. The 16 AseI and 7 DraI fragments were aligned as a single chromosome of about 8,000 kb. The data supported the interpretation that the chromosome is a linear structure. The related strain Streptomyces coelicolor A3(2) M145, recently mapped by H. Kieser, T. Kieser, and D. A. Hopwood (J. Bacteriol. 174:5496-5507, 1992), was compared with S. lividans at the level of the genomic structure by hybridizing the linking cosmids to Southern transfers of PFGE patterns. In spite of little apparent similarity in their restriction patterns, the comparison of the physical maps revealed a common structure with an identical ordering of the cosmid sequences. This conservation of the map order was further confirmed by assigning genetic markers (i.e., cloned genes and DNA elements relevant to the unstable region) to the AseI fragments. PMID- 8501048 TI - Fine-structure analysis of the P7 plasmid partition site. AB - The par region of bacteriophage P7 is responsible for active partition of the P7 plasmid prophage into daughter cells. The cis-acting partition site was defined precisely as a 75-bp sequence that was necessary and sufficient to promote correct segregation of an unstable vector plasmid when the two P7 partition proteins, ParA and ParB, were supplied in trans. Roughly the same region was necessary to exert partition-mediated incompatibility. The minimal site contains an integration host factor (IHF) protein binding site bracketed by regions containing heptamer repeat sequences that individually bind ParB. An additional sequence forms the left boundary of the site. Site-directed mutations in the latter sequence, as well as the IHF motif and the rightmost ParB box, blocked site function. Although the P7 site shares 55% sequence identity with its counterpart in bacteriophage P1, functional interactions between the partition sites and the Par proteins of the two plasmids were entirely species specific in vivo. The P1 sequence has similar IHF and ParB binding motifs, but the left boundary sequence differs radically and may define a point of species-specific contact with the Par proteins. No evidence was found for the existence of a functional P7 analog of the P1 parS core, a small subregion of the P1 site that, in isolation, acts as an enfeebled partition site with modified incompatibility properties. PMID- 8501049 TI - Adhesion and growth rate of Clostridium cellulolyticum ATCC 35319 on crystalline cellulose. AB - The rate of tritiated-thymidine incorporation into DNA was used to estimate Clostridium cellulolyticum H10 growth rates on Avicel cellulose, taking into consideration both the unattached cells and the cells adhered to the substrate. The generation time on cellobiose calculated from the data on cell density (4.5 h) agreed well with the generation time calculated by tritiated-thymidine incorporation (3.8 h). Growth on Avicel cellulose occurred when bacteria were adhered to their substrate; 80% of the biomass was detected on the cellulose. Taking into consideration attached and free bacteria, the generation time as determined by thymidine incorporation was about 8 h, whereas by bacterial-protein estimation it was about 13 h. In addition to the growth rate of the bacteria on the cellulose, the release of adhered cells constituted an important factor in the efficiency of the cellulolysis. The stage of growth influenced adhesion of C. cellulolyticum; maximum adhesion was found during the exponential phase. Under the conditions used, the end of growth was characterized by an acute release of biomass and cellulase activity from the cellulose. An exhaustion of the accessible cellulose could be responsible for this release. PMID- 8501050 TI - The plasmid-encoded urease gene cluster of the family Enterobacteriaceae is positively regulated by UreR, a member of the AraC family of transcriptional activators. AB - Ureolytic clinical isolates of Providencia stuartii, Salmonella spp., and some Escherichia coli strains contain large urease-encoding plasmids. Expression of urease activity from these isolates is induced at least 20-fold by urea. In order to facilitate studies on the regulatory mechanism controlling this urea-inducible expression, the plasmid-encoded urease genes were inserted into the low-copy number vector pRK415, to form pSEF70. Deletion mutagenesis of pSEF70 demonstrated that between 1.3 and 1.6 kb of DNA upstream of ureD (the first of seven urease genes clustered in an operon-like fashion) was required for a urease-positive phenotype. An open reading frame coding for a 34.1-kDa polypeptide was found in the DNA sequence of this upstream region. This open reading frame has been designated ureR, for urease regulator. A urea-inducible promoter region was identified upstream of ureD. Transcription from this promoter was activated only when ureR was present in trans. The predicted ureR gene product contains a helix turn-helix motif and shows significant amino acid similarity to the AraC family of transcriptional activators. We conclude that urea-dependent expression from the plasmid-encoded urease gene cluster requires ureR and that ureR codes for a positive regulatory element controlling transcription of at least one essential urease gene, ureD. PMID- 8501052 TI - Arsenic efflux governed by the arsenic resistance determinant of Staphylococcus aureus plasmid pI258. AB - The arsenic resistance operon of Staphylococcus aureus plasmid pI258 determined lowered net cellular uptake of 73As by an active efflux mechanism. Arsenite was exported from the cells; intracellular arsenate was first reduced to arsenite and then transported out of the cells. Resistant cells showed lower accumulation of 73As originating from both arsenate and arsenite. Active efflux from cells loaded with arsenite required the presence of the plasmid-determined arsB gene. Efflux of arsenic originating as arsenate required the presence of the arsC gene and occurred more rapidly with the addition of arsB. Inhibitor studies with S. aureus loaded with arsenite showed that arsenite efflux was energy dependent and appeared to be driven by the membrane potential. With cells loaded with 73AsO4(3 ), a requirement for ATP for energy was observed, leading to the conclusion that ATP was required for arsenate reduction. When the staphylococcal arsenic resistance determinant was cloned into Escherichia coli, lowered accumulation of arsenate and arsenite and 73As efflux from cells loaded with arsenate were also found. Cloning of the E. coli plasmid R773 arsA gene (the determinant of the arsenite-dependent ATPase) in trans to the S. aureus gene arsB resulted in increased resistance to arsenite. PMID- 8501051 TI - Flagellin gene transcription in Bordetella bronchiseptica is regulated by the BvgAS virulence control system. AB - The products of the bvgAS locus activate expression of a majority of the known Bordetella virulence factors but also exert negative control over a class of genes called vrg genes (bvg-repressed genes). BvgAS negatively controls the production of flagella and the phenotype of motility in Bordetella bronchiseptica. In this study flaA, the flagellin gene, was cloned and characterized to facilitate studies of this negative control pathway. An internal flaA probe detected hybridizing sequences on genomic Southern blots of Bordetella pertussis, Bordetella parapertussis, and Bordetella avium, although B. pertussis and B. parapertussis are nonmotile. FlaA is similar to the FliC flagellins of Salmonella typhimurium and Escherichia coli, and flaA complemented an E. coli flagellin mutant. Insertional inactivation of the chromosomal flaA locus eliminated motility, which was restored by complementation with the wild-type locus. Analysis of flaA mRNA production by Northern (RNA) blotting and primer extension indicated that negative regulation by BvgAS occurs at the level of transcription. The transcriptional start site of flaA mapped near a consensus site for the alternative sigma factor, sigma F, encoded by fliA in E. coli and S. typhimurium. Consistent with a role for a fliA analog in B. bronchiseptica, transcriptional activation of a flaA-lacZ fusion in E. coli required fliA and a flaA-linked locus designated frl.frl also efficiently complemented mutations in the flagellar master regulatory locus, flhDC, of E. coli. Our analysis of the motility phenotype of B. bronchiseptica suggests that the Bordetella virulence control system mediates transcriptional control of flaA through a regulatory hierarchy that includes the frl locus and an alternative sigma factor. PMID- 8501053 TI - Analysis of the Ros repressor of Agrobacterium virC and virD operons: molecular intercommunication between plasmid and chromosomal genes. AB - The virulence genes of the Agrobacterium tumefaciens Ti plasmid are regulated both positively and negatively. The products of the genes of the virC and virD operons play an important role in host specificity and T-DNA processing. These operons are transcribed in opposite directions and therefore bear diametrically oriented promoters. These promoters are positively regulated by the VirG protein, which is believed to be activated through phosphorylation by a histidine kinase encoded by the virA gene. The virC and virD operons are also regulated by a 15.5 kDa repressor protein encoded by the ros chromosomal gene. A mutation in ros causes the constitutive expression of virC and virD in the complete absence of the VirG protein. It appears, therefore, that the Ros repressor interacts with the regulatory region of these operons. The Ros repressor is shown here to bind to an upstream sequence (Ros box) comprising 40 bp bearing a 9-bp inverted repeat, TATATTTCA/TGTAATATA, in the promoter region of these operons. The affinity for this sequence is specific and tenacious, since the addition of at least a 20,000-fold excess of competitor DNA failed to remove the Ros protein coding sequence from the Ros box. DNase I footprint analysis showed that the Ros box overlaps the binding site of VirG (Vir box). This result suggests that virC and virD transcription is modulated by Ros and VirG proteins. PMID- 8501054 TI - Amino-acylation site mutations in amino acid-activating domains of surfactin synthetase: effects on surfactin production and competence development in Bacillus subtilis. AB - The part of the srfA operon of Bacillus subtilis that contains the region required for competence development is composed of the first four amino acid activating domains which are responsible for the incorporation of Glu, Leu, D Leu, and Val into the peptide moiety of the lipopeptide surfactin. Ser-to-Ala substitutions were made in the amino-acylation site of each domain, and their effects on surfactin production and competence development were examined. All of the mutations conferred a surfactin-negative phenotype, supporting the finding that the conserved Ser in the amino-acylation site is required for peptide synthesis. However, none of the mutations affected significantly competence development or the expression of a lacZ fusion to the late competence operon comG. This, coupled with recent findings that only the fourth, Val-activating, domain is required for competence, suggests that some activity, other than amino acylation and perhaps unrelated to peptide synthesis, possessed by the fourth domain is involved in the role of srfA in regulating competence development. PMID- 8501055 TI - LcrG, a secreted protein involved in negative regulation of the low-calcium response in Yersinia pestis. AB - The purpose of this study was to define the function of LcrG, the product of the first gene in the lcrGVHyopBD operon of the low-Ca(2+)-response (LCR) virulence plasmid of Yersinia pestis. We created a Y. pestis strain having an in-frame deletion in lcrG. This nonpolar mutant had an abnormal LCR growth phenotype: it was unable to grow at 37 degrees C in the presence of 2.5 mM Ca2+ ("Ca2+ blind") but was able to grow at 37 degrees C when 18 mM ATP was present. At 37 degrees C it failed to downregulate the expression and secretion of its truncated product (LcrG), V antigen, and YopM. All of these mutant properties were complemented by plasmids carrying normal lcrG. However, a nonpolar lcrE mutation and an lcrH mutation (both also causing a Ca(2+)-blind phenotype) were not complemented in this way. The Y. pestis parent strain expressed LcrG at 37 degrees C in the presence and absence of Ca2+ and transported it to the medium when Ca2+ was absent. We identified two LCR-regulated loci, lcrD and yscDEF, required for this transport. Complementation analysis of the Y. pestis lcrR strain previously shown to lack the expression of LcrG showed that the loss of LcrG but not of LcrR caused the Ca(2+)-blind phenotype of that mutant. Taken together, the results show that LcrG is a negative regulator of the LCR, perhaps functioning in Ca2+ sensing along with LcrE. PMID- 8501056 TI - Positive regulation of phenolic catabolism in Agrobacterium tumefaciens by the pcaQ gene in response to beta-carboxy-cis,cis-muconate. AB - An Escherichia coli system for generating a commercially unavailable catabolite in vivo was developed and was used to facilitate molecular genetic studies of phenolic catabolism. Introduction of the plasmid-borne Acinetobacter pcaHG genes, encoding the 3,4-dioxygenase which acts on protocatechuate, into E. coli resulted in bioconversion of exogenously supplied protocatechuate into beta-carboxy cis,cis-muconate. This compound has been shown to be an inducer of the protocatechuate (pca) genes required for catabolism of protocatechuate to tricarboxylic acid cycle intermediates in Rhizobium leguminosarum biovar trifolii. The E. coli bioconversion system was used to explore regulation of the pca genes in a related bacterium, Agrobacterium tumefaciens. The pcaD gene, which encodes beta-ketoadipate enol-lactone hydrolase, from A. tumefaciens A348 was cloned and was shown to be adjacent to a regulatory region which responds strongly to beta-carboxy-cis,cis-muconate in E. coli. Site-specific insertional mutagenesis of the regulatory region eliminated expression of the pcaD gene in E. coli. When the mutation was incorporated into the A. tumefaciens chromosome, it eliminated expression of the pcaD gene and at least three other pca genes as well. The regulatory region was shown to activate gene expression in trans. The novel regulatory gene was termed pcaQ to differentiate it from pca regulatory genes identified in other microbes, which bind different metabolites. PMID- 8501057 TI - Multiple effects of lcrD mutations in Yersinia pestis. AB - Plasmid pCD1 of Yersinia pestis contains a low-calcium response stimulon responsible for the temperature- and calcium-regulated expression and secretion of proteins involved in virulence, which include the V antigen and Yops. We have previously shown that insertional inactivation of the bicistronic lcrDR operon abolished the calcium requirement for growth at 37 degrees C and reduced expression of the V antigen and Yops. In this study, we constructed and characterized three mutants having nonpolar lcrD deletions. All three mutants lost the two main low-calcium response properties: a calcium requirement for growth at 37 degrees C and strong expression of the V antigen and Yops. The effects on virulence gene expression occurred at both the levels of transcription and secretion. The growth, transcription, and secretion defects could be at least partially complemented for two of the lcrD mutants by providing lcrD in trans. A third mutant could not be complemented, and a plasmid carrying this mutation had a dominant negative effect over normal LcrD function. In the three mutants, the amount of mutant LcrD protein detectable in immunoblots was inversely related to the amount of complementation. Taken together, these data indicate that LcrD function involves the interaction of LcrD with another molecule. PMID- 8501058 TI - Heat shock proteins DnaJ, DnaK, and GrpE stimulate P1 plasmid replication by promoting initiator binding to the origin. AB - Binding of the P1-encoded protein RepA to the origin of P1 plasmid replication is essential for initiation of DNA replication and for autoregulatory repression of the repA promoter. Previous studies have shown defects in both initiation and repression in hosts lacking heat shock proteins DnaJ, DnaK, and GrpE and have suggested that these proteins play a role in the RepA-DNA binding required for initiation and repression. In this study, using in vivo dimethyl sulfate footprinting, we have confirmed the roles of the three heat shock proteins in promoting RepA binding to the origin. The defects in both activities could be suppressed by increasing the concentration of wild-type RepA over the physiological level. We also isolated RepA mutants that were effective initiators and repressors without requiring the heat shock proteins. These data suggest that the heat shock proteins facilitate both repression and initiation by promoting only the DNA-binding activity of RepA. In a similar plasmid, F, initiator mutants that confer heat shock protein independence for replication were also found, but they were defective for repression. We propose that the initiator binding involved in repression and the initiator binding involved in initiation are similar in P1 but different in F. PMID- 8501059 TI - High-frequency transformation of a methylotrophic yeast, Candida boidinii, with autonomously replicating plasmids which are also functional in Saccharomyces cerevisiae. AB - We have developed a transformation system which uses autonomous replicating plasmids for a methylotrophic yeast, Candida boidinii. Two autonomous replication sequences, CARS1 and CARS2, were newly cloned from the genome of C. boidinii. Plasmids having both a CARS fragment and the C. boidinii URA3 gene transformed C. boidinii ura3 cells to Ura+ phenotype at frequencies of up to 10(4) CFU/micrograms of DNA. From Southern blot analysis, CARS plasmids seemed to exist in polymeric forms as well as in monomeric forms in C. boidinii cells. The C. boidinii URA3 gene was overexpressed in C. boidinii on these CARS vectors. CARS1 and CARS2 were found to function as an autonomous replicating element in Saccharomyces cerevisiae as well. Different portions of the CARS1 sequence were needed for autonomous replicating activity in C. boidinii and S. cerevisiae. C. boidinii could also be transformed with vectors harboring a CARS fragment and the S. cerevisiae URA3 gene. PMID- 8501060 TI - Functional characterization of a replication initiator protein. AB - Functional domains in the RepI replication initiator protein have been identified by classical and site-directed mutagenesis techniques. Mutations conferring an increase in plasmid copy number contained alterations in a key position of a putative helix-turn-helix DNA binding motif. The mutations did not appear to affect autorepressing functions. Regions of RepI important for autorepression were localized as well. Two classes of mutations resulting in diminished autorepression functions were identified. One class was distinguished by an elevated copy number, while the other class remained at the wild-type copy number level. Analysis of the various mutations leading to changes in copy number or autorepressing functions suggest that in some cases the autorepression and initiating functions of the RepI protein are separable. Finally, analysis with deletion clones suggests that the trans-acting autorepressing functions of RepI might depend on intermolecular coupling control. PMID- 8501061 TI - Rhizobium fredii and Rhizobium meliloti produce 3-deoxy-D-manno-2-octulosonic acid-containing polysaccharides that are structurally analogous to group II K antigens (capsular polysaccharides) found in Escherichia coli. AB - The polysaccharide components from cultured cells of Rhizobium fredii USDA205 and Rhizobium meliloti AK631 were extracted with hot phenol-water and separated by repetitive gel filtration chromatography. Polyacrylamide gel electrophoresis, nuclear magnetic resonance spectrometry, and gas chromatography analyses showed that both of these bacterial species produce unique polysaccharides that contain a high proportion of 3-deoxy-D-manno-2-octulosonic acid (Kdo). These polysaccharides, which constituted a major portion of the extracted carbohydrate, are not excreted into the growth media (i.e., they are not extracellular polysaccharides) and are structurally distinct from the lipopolysaccharides. The primary structure of the preponderant polysaccharide from R. fredii USDA205 was determined by high-performance anion-exchange liquid chromatography, nuclear magnetic resonance spectrometry, fast atom bombardment-mass spectrometry, and gas chromatography-mass spectrometry; it consists of repeating units of [-->3)-alpha D-Galp-(1-->5)-beta-D-Kdop-(2-->]n. This molecule is structurally analogous to the constituents of one subgroup of K antigens (capsular polysaccharides) produced by Escherichia coli. Polysaccharides of this type have not previously been identified as components of rhizobial cells. The Kdo-containing polysaccharide from R. meliloti, which has not been completely characterized, appears to be structurally related to that of R. fredii. PMID- 8501062 TI - Identification, sequencing, and targeted mutagenesis of a DNA polymerase gene required for the extreme radioresistance of Deinococcus radiodurans. AB - Deinococcus radiodurans and other species of the same genus share extreme resistance to ionizing radiation and many other agents that damage DNA. Two different DNA damage-sensitive strains generated by chemical mutagenesis were found to be defective in a gene that has extended DNA and protein sequence homology with polA of Escherichia coli. Both mutant strains lacked DNA polymerase, as measured in activity gels. Transformation of this gene from wild type D. radiodurans restored to the mutants both polymerase activity and DNA damage resistance. A technique for targeted insertional mutagenesis in D. radiodurans is presented. This technique was employed to construct a pol mutant isogenic with the wild type (the first example of targeted mutagenesis in this eubacterial family). This insertional mutant lacked DNA polymerase activity and was even more sensitive to DNA damage than the mutants derived by chemical mutagenesis. In the case of ionizing radiation, the survival of the wild type after receiving 1 Mrad was 100% while survival of the insertional mutant extrapolated to 10(-24). These results demonstrate that the gene described here encodes a DNA polymerase and that defects in this pol gene cause a dramatic loss of resistance of D. radiodurans to DNA damage. PMID- 8501063 TI - Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli. AB - We demonstrate here that Escherichia coli synthesizes two different glycinamide ribonucleotide (GAR) transformylases, both catalyzing the third step in the purine biosynthetic pathway. One is coded for by the previously described purN gene (GAR transformylase N), and a second, hitherto unknown, enzyme is encoded by the purT gene (GAR transformylase T). Mutants defective in the synthesis of the purN- and the purT-encoded enzymes were isolated. Only strains defective in both genes require an exogenous purine source for growth. Our results suggest that both enzymes may function to ensure normal purine biosynthesis. Determination of GAR transformylase T activity in vitro required formate as the C1 donor. Growth of purN mutants was inhibited by glycine. Under these conditions GAR accumulated. Addition of purine compounds or formate prevented growth inhibition. The regulation of the level of GAR transformylase T is controlled by the PurR protein and hypoxanthine. PMID- 8501064 TI - Physical and functional characterization of the Bacillus subtilis spoIIM gene. AB - The spoIIM locus of Bacillus subtilis is the most recently discovered of six genetic loci in which mutations can prevent the synthesis of a normal asymmetric septum or prevent migration of the septal structure to engulf the forespore compartment of the sporangium. Ultrastructure studies of a spoIIM mutant confirmed a block prior to the completion of engulfment. Introduction of a spoIIM mutation into a panel of strains containing lacZ fusions belonging to different regulatory classes allowed us to determine that the spoIIM gene product is required for the efficient expression of genes transcribed by sigma G-associated RNA polymerase but is not required for the expression of sigma F-controlled genes, including spoIIIG, which encodes sigma G. The results of complementation studies, gene disruption analysis, and DNA sequencing revealed that the spoIIM locus contains a single sporulation-essential gene encoding a polypeptide with a predicted molecular mass of 24,850 Da. The predicted spoIIM gene product is highly hydrophobic and very basic, and it does not exhibit significant homology to sequence files in several major data bases. PMID- 8501065 TI - Evidence that the spoIIM gene of Bacillus subtilis is transcribed by RNA polymerase associated with sigma E. AB - We have investigated the temporal and spatial regulation of spoIIM, a gene of Bacillus subtilis whose product is required for complete septum migration and engulfment of the forespore compartment during sporulation. The spoIIM promoter was found to become active about 2 h after the initiation of sporulation. The effects of mutations on the expression of a spoIIM-lacZ fusion were most consistent with its utilization by sigma-E-associated RNA polymerase (E sigma E). A unique 5' end of the in vivo spoIIM transcript was detected by primer extension analysis and was determined to initiate at the appropriate distance from a sequence conforming very closely to the consensus for genes transcribed by E sigma E. A partially purified preparation of E sigma E produced a transcript in vitro that initiated at the same nucleotide as the primer extension product generated from in vivo RNA. Ectopic induction of sigma E synthesis during growth resulted in the immediate and strong expression of a spoIIM-lacZ fusion, but an identical fusion was completely unresponsive to induced synthesis of either sigma F or sigma G under similar conditions. The results of plasmid integration excision experiments in which the spoIIM gene was reversibly disrupted by a temperature-sensitive integrational vector suggested that spoIIM expression is required in the forespore compartment, but direct examination of subcellular fractions enriched for mother cell or forespore material indicated that spoIIM expression cannot be confined to the forespore. We conclude that spoIIM is a member of the sigma E regulon and that it may be transcribed exclusively by E sigma E. We discuss the implications of this conclusion for models in which activation of sigma E in the mother cell is proposed to be a part of the mechanism responsible for initiating separate programs of gene activity in the two sporangium compartments. PMID- 8501066 TI - High-efficiency gene inactivation and replacement system for gram-positive bacteria. AB - A system for high-efficiency single- and double-crossover homologous integration in gram-positive bacteria has been developed, with Lactococcus lactis as a model system. The system is based on a thermosensitive broad-host-range rolling-circle plasmid, pG+host5, which contains a pBR322 replicon for propagation in Escherichia coli at 37 degrees C. A nested set of L. lactis chromosomal fragments cloned onto pG+host5 were used to show that the single-crossover integration frequency was logarithmically proportional to the length of homology for DNA fragments between 0.35 and 2.5 kb. Using random chromosomal 1-kb fragments, we showed that homologous integration can occur along the entire chromosome. We made use of the reported stimulatory effect of rolling-circle replication on intramolecular recombination to develop a protocol for gene replacement. Cultures were first maintained at 37 degrees C to select for a bacterial population enriched for plasmid integrants; activation of the integrated rolling-circle plasmid by a temperature shift to 28 degrees C resulted in efficient plasmid excision by homologous recombination and replacement of a chromosomal gene by the plasmid-carried modified copy. More than 50% of cells underwent replacement recombination when selection was applied for the replacing gene. Between 1 and 40% of cells underwent replacement recombination when no selection was applied. Chromosomal insertions and deletions were obtained in this way. These results show that gene replacement can be obtained at an extremely high efficiency by making use of the thermosensitive rolling-circle nature of the delivery vector. This procedure is applicable to numerous gram-positive bacteria. PMID- 8501067 TI - Regulation of cohesion-dependent cell interactions in Myxococcus xanthus. AB - Myxococcus xanthus has two nearly independent genetic systems, A and S, which appear to mediate adventurous (single-cell) movement and social (group) movement, respectively. In addition to a notable reduction in group movement, social motility mutants exhibit decreased biofilm formation, cell cohesion, dye binding, fibril production, and fruiting body formation. The stk-1907 allele, containing transposon Tn5 insertion omega DK1907, was introduced into wild-type cells and many social motility mutants. This allele, which was epistatic to most social motility mutations, caused wild-type and most mutant cells to exhibit increased group movement, cell cohesion, dye binding, and production of cell surface fibrils. The presence of the stk-1907 allele in dsp mutants, which almost completely lack cell surface fibrils, did not result in these phenotypic changes; therefore, stk-1907 is hypostatic to dsp mutations. Those mutants which exhibited increased group movement and cell cohesion with the stk-1907 allele also had increased fruiting body formation, but no significant changes in spore production were observed. These results suggest that fibrils may mediate cell cohesion, dye binding, and group movement. Additionally, the results suggest that the dsp locus contains genes involved in subunit synthesis, transport, and/or assembly of fibrils. The wild-type and mutant alleles of stk were cloned and studied in merodiploids. The mutant allele is recessive, suggesting that Tn5 omega DK1907 caused a null mutation in a gene which acts as a negative regulator of fibril synthesis. The stk-1907 allele appears to cause utilization of the A motility system for group movement, possibly because of increased fibril production. PMID- 8501068 TI - Effect of dsp mutations on the cell-to-cell transmission of CsgA in Myxococcus xanthus. AB - The dsp locus contains genes involved in the subunit synthesis and/or assembly of fibrils that radiate outward from the Myxococcus xanthus cell surface and attach to other cells. The csgA gene encodes an extracellular protein morphogen which is essential for fruiting body development. The question of whether fibrils are involved in the transmission of CsgA to adjacent cells was investigated in three ways. First, the dsp and csgA mutants were mixed in a ratio of 1:1 and allowed to develop; fruiting bodies containing spores derived from the csgA mutant were formed, suggesting efficient CsgA transfer. Second, the csgA mutation affected expression of many developmentally regulated genes differently from the way dsp affected their expression. Third, the expression of one developmentally regulated gene, which was partially expressed in csgA and dsp backgrounds, was almost completely inhibited in the presence of both mutations, suggesting that its promoter is regulated independently by two distinct stimuli, one that is csgA dependent and one that is dsp dependent. Together these results argue that fibrils are not necessary for cell-to-cell transmission or perception of CsgA, and their precise function remains unknown. PMID- 8501069 TI - The acetyl substituent of succinoglycan is not necessary for alfalfa nodule invasion by Rhizobium meliloti Rm1021. AB - Rhizobium meliloti Rm1021 requires a Calcofluor-binding exopolysaccharide, termed succinoglycan or EPS I, to invade alfalfa nodules. We have determined that a strain carrying a mutation in the exoZ locus produces succinoglycan that lacks the acetyl substituent. The exoZ mutant nodules alfalfa normally. PMID- 8501071 TI - Structures of the modified folates in the extremely thermophilic archaebacterium Thermococcus litoralis. AB - The chemical structures of the two modified folates present in Thermococcus litoralis were established. These compounds, each containing a core structure of 1-[4-[[1-(2-amino-7-methyl- 4-oxo-6-pteridinyl)-ethyl]amino]phenyl]-1-deoxy-[1 alpha-D- ribofuranosyl]-ribitol, were characterized. The five position of the ribose in this core structure was beta-linked to the C-1 of a poly-beta (1-->4)N acetylglucosamine having a chain length of four or five N-acetylglucosamine residues. Thus, these compounds are N-acetylglucosamine homologs of the modified folates found in Pyrococcus furiosus. PMID- 8501070 TI - Temperature-sensitive sporulation caused by a mutation in the Bacillus subtilis secY gene. AB - A thermosensitive sporulation mutant of Bacillus subtilis containing a mutation in the secY gene was isolated and characterized. No asymmetric septum specific to the sporulation was detected by electron microscopy at the nonpermissive temperature, indicating that the block occurred at a very early stage of sporulation. Furthermore, competence development in the mutant cell was affected even at the sporulation-proficient temperature. It is assumed that the SecY protein of B. subtilis has multiple roles both in the regulation of spore formation and in stationary-phase-associated phenomena. PMID- 8501072 TI - The Chlamydia trachomatis Mip-like protein is a lipoprotein. AB - The Mip-like protein of Chlamydia trachomatis is similar to the Mip protein of Legionella pneumophila and may be equally important for the initiation of intracellular infection. This article presents data which identify the chlamydial Mip-like protein as a lipoprotein. The amino acid sequence of the Mip-like protein contains a signal peptidase II recognition sequence, as is seen in procaryotic lipoproteins. Palmitic acid was incorporated into the recombinant chlamydial Mip-like protein. Globomycin, known to inhibit signal peptidase II, inhibited processing of the recombinant Mip-like protein. Labelling of chlamydial organisms with palmitic acid revealed incorporation into the native Mip-like protein. PMID- 8501073 TI - Spatial and temporal accumulation of mRNAs encoding two common lignin peroxidases in Phanerochaete chrysosporium. AB - Accumulation of peroxidases and their mRNAs was localized in colonies of Phanerochaete chrysosporium sandwiched between perforated polycarbonate membranes. Northern (RNA) blot analyses of colonial rings and in situ hybridizations with specific probes for manganese(II)-dependent peroxidase (MnP 1) and lignin peroxidase (LiP H8) mRNAs indicated that the expression of MnP-1 and Lip H8 genes started simultaneously in the central area of 3-day-old colonies. With time the signals for both transcripts spread to more-peripheral areas while decreasing in intensity. Furthermore, the appearance of MnP protein, as detected with specific immune serum, immediately followed accumulation of the MnP-1 mRNA transcript. However, LiP protein could be detected only some time after accumulation of LiP H8 mRNA. PMID- 8501074 TI - Localization of the codA gene on the Escherichia coli chromosome. PMID- 8501075 TI - Physical map location of the new artPIQMJ genes of Escherichia coli, encoding a periplasmic arginine transport system. PMID- 8501076 TI - Physical mapping of the scattered methionine genes on the Escherichia coli chromosome. AB - Methionine is an important amino acid which acts not only as a substrate for protein elongation but also as the initiator of protein synthesis. The genes of the met regulon, which consists of 10 biosynthetic genes (metA, metB, metC, metE, metF, metH, metK, metL, metQ, and metX), two regulatory genes (metJ and metR), and the methionyl tRNA synthetase gene (metG), are scattered throughout the chromosome. The only linked genes are metK and metX at 63.6 min, metE and metR at 86.3 min, and the metJBLF gene cluster at 89 min. metBL form the only met operon. PMID- 8501077 TI - New partnerships. PMID- 8501078 TI - Pemberton osteotomy for residual acetabular dysplasia in children who have congenital dislocation of the hip. AB - We reviewed the results for fifty-two hips in forty-two patients who had had a Pemberton pericapsular osteotomy between 1968 and 1984 as treatment for residual acetabular dysplasia of the hip. The average age of the patients at the time of the osteotomy was four years. The average duration of follow-up was ten years. At the time of the most recent follow-up, forty-two of the fifty-two hips had a rating of Severin class IA, an essentially normally developed hip. The results of the Pemberton osteotomy were unpredictable if there had been necrosis of the femoral head (without infection) preoperatively. We believe that the Pemberton osteotomy is a safe, effective procedure for the treatment of acetabular dysplasia in patients who have congenital dislocation of the hip. PMID- 8501079 TI - One-stage release of congenital circumferential constriction bands. AB - A one-stage release of circumferential congenital constriction bands was performed in four extremities (three patients). No wound problems occurred, even when there had been marked swelling of the extremity distal to the band. The one stage release facilitated postoperative care, and there was no need for additional periods of anesthesia or for additional operations, which are necessary when this problem is treated with a release performed in two or three stages. PMID- 8501080 TI - Congenital vertebral displacement. AB - We defined congenital vertebral displacement as displacement at a single vertebral level that results in an abrupt displacement of the neural canal. We reviewed the data on 642 patients who had congenital vertebral abnormalities and identified ten who had congenital vertebral displacement. There were two patterns of deformity: Type A (eight patients) consisted of displacement in the sagittal plane only, and Type B (two patients), rotatory, transverse, and sagittal displacement. The spinal deformity was usually noted in infancy. Neurological deficits were identified at the time of presentation or developed later in six patients. Two patients had a sudden onset of paraplegia after slight trauma, two had a gradual onset of neurological abnormalities, and two had neurological abnormalities when they were first seen. Three patients had congenital anomalies of the spinal cord. We found marked mechanical instability intraoperatively in five patients, and we believe that the instability in combination with compression of the spinal cord resulted in myelopathy. We recommend combined anterior and posterior arthrodesis of the spine for the treatment of this disorder. We believe that decompression of the spinal cord is indicated for patients who have a neurological deficit of recent onset or a progressive neurological deficit. Decompression of the spinal cord may also be indicated for the treatment of long-standing deficits after spinal stability has been obtained. PMID- 8501081 TI - Revision of the acetabular component without cement after total hip arthroplasty. Three to six-year follow-up. AB - One hundred and thirty-eight consecutive revisions of an acetabular component were performed in 132 patients between 1983 and 1986. The revision prosthesis was a hemispherical component that was coated with porous titanium mesh and was secured to the pelvis with a variable number of screws. There were seventy-five women and fifty-seven men, and the mean age at the time of the revision was fifty two years (range, twenty to seventy-nine years). Due to defects in the acetabulum, 80 per cent of the hips were treated with bone grafts, usually a mixture of local autogenous graft and freeze-dried allograft. One hundred and twenty-four patients (129 hips) were available for follow-up, at a mean of forty four months (range, thirty-six to eighty months). Seven hips (5 per cent) were revised again: four because of infection and three because of instability. There were no revisions for loosening without infection, and none of the components migrated in the absence of infection. Radiolucent lines were common and usually corresponded to regions in which allograft had been used. All bone grafts united by twelve months. Non-contained medial grafts underwent a phenomenon of resorption, consolidation, and remodeling to a sclerotic rim by twenty-four months. There were no complications related to placement of the screws. The results in this series were superior to results of revisions of acetabular components with the use of cement, which were associated with rates of failure of almost 10 per cent after a similar duration of follow-up. The technique of maximization of host-bone coverage and of packing of all defects with cancellous autogenous graft or allograft, or both, was successful for all classes of acetabular deficiencies. PMID- 8501082 TI - Long-term complications after total knee arthroplasty with or without resurfacing of the patella. AB - The long-term complications related to the patella were retrospectively evaluated for 891 knees (684 patients) that had had a total arthroplasty, with or without resurfacing of the patella, with use of an unconstrained, condylar, posterior cruciate-preserving prosthesis. The study population comprised two groups of patients who were similar in size, age, sex distribution, and diagnosis. One group (396 knees [303 patients]) had had a total knee arthroplasty with patellar resurfacing and the other group (495 knees [381 patients]) had had the same procedure without resurfacing. The average duration of follow-up was six and one half years (range, two to fifteen years). The decision to resurface the patella was based on subjective inspection of the articular surface and on assessment of patellar tracking at the time of the operation. Resurfacing was performed if there was loss of cartilage, exposed bone, gross surface irregularities, or tracking abnormalities. Complications occurred an average of three years (range, immediately postoperatively to nine years) after the operation in the group that had had resurfacing and an average of four years (range, immediately post operatively to ten years) postoperatively in the group that had not had resurfacing. In the group that had had resurfacing, there was loosening of the patellar component in five knees, patellar subluxation in four knees, fracture of the patella in three knees, rupture of the patellar tendon in three knees, and chronic peripatellar pain in one knee. In the group that had not had resurfacing, the complications included patellar subluxation in five knees, rupture of the patellar tendon in two knees, and chronic peripatellar pain in fifty-one knees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501083 TI - Evaluation of the medial soft-tissue restraints of the extensor mechanism of the knee. AB - We performed an anatomical dissection of the medial soft-tissue retinacular fibers that restrain lateral patellar displacement and found that the medial patellofemoral ligament inserts not only on the patella but also on the undersurface of the distal aspect of the quadriceps mechanism. The deep capsular layer contained substantial retinacular fibers that were associated with the medial patellomeniscal ligament. Functional studies of the relative contributions of the medial soft-tissue restraints in the prevention of lateral patellar displacement were also performed. Twenty-five fresh-frozen specimens of the knee, obtained after amputations (nineteen specimens) or from cadavera (six specimens) were tested biomechanically on a universal testing instrument. We ranked the soft tissue restraints, in order of their relative contributions to the restraining force, on the basis of the percentage of force provided by the retinacular and ligamentous tissue that resisted the lateral displacement of the patella. The medial patellofemoral ligament, although varying in size and importance, was found to be the major medial soft-tissue restraint that prevented lateral displacement of the distal knee-extensor mechanism, contributing an average of 53 per cent of the total force. The patellomeniscal ligament and associated retinacular fibers in the deep capsular layer of the knee, which were previously thought to be functionally unimportant in the stabilization of the patella, contributed an average of 22 per cent of the total force. The previously described retinacular fibers (the patellotibial band) were functionally unimportant in the prevention of lateral displacement. PMID- 8501084 TI - The effects of sectioning of the posterior cruciate ligament and the posterolateral complex on the articular contact pressures within the knee. AB - Articular contact pressures in ten cadaveric knees with intact ligaments were measured with the use of film and a model that simulated non-weight-bearing resistive extension of the knee. The measurements were repeated after sequential sectioning of the posterior cruciate ligament and the posterolateral complex (the posterolateral capsule, the popliteus muscle and tendon, and the lateral collateral ligament). Patellofemoral pressures and quadriceps load were most significantly elevated after combined sectioning of the posterior cruciate ligament and the posterolateral complex. Medial compartment pressure was significantly elevated after sectioning of the posterior cruciate ligament. The results coincided with, and may partially explain, the clinical findings associated with these types of ligamentous injuries. PMID- 8501085 TI - Use of a tourniquet in the internal fixation of fractures of the distal part of the fibula. A prospective, randomized trial. AB - A prospective, randomized trial was undertaken to determine the rate of complications after the use of a tourniquet during open reduction and internal fixation of simple, closed fractures of the distal part of the fibula. Forty patients were operated on with use of a tourniquet (Group 1) and forty patients, without use of a tourniquet (Group 2). The average duration of the operation was significantly different between the two groups (41 +/- 9 minutes for Group 1 compared with 53 +/- 12 minutes for Group 2 [p = 0.026]). There were more complications in the patients in Group 1, two of whom had an isolated deep-vein thrombosis of the calf. The wound was possibly infected in eleven patients (seven in Group 1 and four in Group 2 [p < 0.05]) and frankly infected in three patients, all in Group 1 (p < 0.05). The plaster-of-Paris cast needed to be changed in three patients from Group 1. The patients in Group 1 returned to work an average of one week later than those in Group 2. The mean duration of follow up was eighteen months (range, nine to thirty-two months). Given the lower prevalence of postoperative complications and the shorter time to recovery for the patients in Group 2, we believe that it is justified not to use a tourniquet in the operative treatment of simple, isolated fibular fractures. PMID- 8501086 TI - Scanning electron-microscopic and magnetic resonance-imaging studies of injuries to the patellofemoral joint after acute transarticular loading. AB - To examine the effects of transarticular loading on articular cartilage and subchondral bone, we used a canine model that we had developed previously, in which a standardized load of approximately 2000 newtons is delivered across the patellofemoral joint. The purpose of the study was to define and describe the initial changes, as seen on histopathological and magnetic resonance-imaging studies, that occur in the early stages after injury to the joint by transarticular loading. Scanning electron microscopy was used to define the extent and characteristics of the fractures produced in the subchondral bone of four patellae that were examined on the day of loading. We found multiple, extensive fractures through the zone of calcified cartilage and the subchondral bone, frequently with step-off displacement, and with little or no change in the gross appearance of the articular cartilage. Specimens from four patellae were examined histologically two weeks after loading, and the observed changes were correlated with those that had been demonstrated by scanning electron microscopy. Fractures through the zone of calcified cartilage and the subchondral bone, with step-off displacement, were prominent. Clefts were present in the surface of the articular cartilage and, in some areas, there was a focal loss of proteoglycan from the extracellular matrix, as indicated by the complete absence of staining with safranin O. Six dogs were examined one year after loading. There was healing of the subchondral fractures and restoration of proteoglycan in the extracellular matrix. However, superficial clefts and fissures were still present in the articular cartilage. Sequential magnetic resonance-imaging studies were also carried out on these six dogs, at two, eight, sixteen, thirty-six, and fifty-two weeks after loading. Two weeks after loading, all knees had soft-tissue swelling, effusion, and a decreased marrow signal in the medullary cavity of the patella. The decreased marrow signal and effusion were still present eight weeks after the impact, and then the findings gradually returned to normal. One year after loading, it was found that the histopathological changes had not been progressive; in fact, they had been ameliorated and, to some extent, reversed by repair processes. The early, severe magnetic resonance-imaging changes had also been reversed, so that this study demonstrated normal findings by one year after loading. PMID- 8501087 TI - Antibiotic-leaching from polymethylmethacrylate beads. AB - Aminoglycoside-impregnated polymethylmethacrylate beads, which are used to deliver antibiotic directly to infected sites in the musculoskeletal system, are available as a manufactured product or they can be mold-made by a pharmacy or hand-rolled by the orthopaedist in the operating suite. We investigated the leaching of antibiotic from each of these types of beads. Our hypothesis was that the elutions of antibiotic from the three types of beads are similar. Three study groups (hand-made, mold-made, and manufactured beads), each composed of four five bead subsets, were formed so that twenty beads of each type were tested. Each bead was leached daily in a two-milliliter aliquot of normal saline solution throughout a sixty-day period, and the aminoglycoside concentration in twenty of these aliquots was determined. Analysis of variance showed no statistically significant differences when the antibiotic elutions within each subset, between the different subsets, and between the three groups were compared. The clinically important finding of this investigation is that the leaching characteristics of the three types of aminoglycoside-impregnated beads are equivalent when the beads have been fabricated out of comparable materials. PMID- 8501088 TI - Reflex sympathetic dystrophy after operative procedures on the lumbar spine. AB - Between July 1987 and April 1991, reflex sympathetic dystrophy developed in eleven patients after a posterior operation on the lumbar spine. The average age of the patients was forty-four years (range, twenty-eight to sixty years). The preoperative diagnosis had been lumbar spondylolisthesis or lumbar instability, associated with degenerative disc disease or with osteoarthrosis of a facet joint. Ten patients had posterior stabilization with bilateral arthrodesis and interpedicular fixation, with use of plates or screws; the remaining patient had a posterior hemilaminotomy of the fourth and fifth lumbar vertebrae, partial discectomy, and foraminal decompression of the fifth lumbar-nerve root. After the operation, all patients had burning pain, vasomotor dysfunction, and dystrophic changes in the lower limb and foot; in four patients, the symptoms were bilateral. The symptoms began four days to twenty weeks after the operation. The patients were followed for nine months to four years. Treatment was most successful in four of six patients who had had at least one nerve-block of the sympathetic lumbar trunk in addition to physiotherapy. PMID- 8501089 TI - The plantar incision for procedures involving the forefoot. An evaluation of one hundred and fifty incisions in one hundred and fifteen patients. AB - Between 1984 and 1990, 172 plantar incisions were used in 137 patients. Eighty nine of these patients returned for a personal interview and examination, twenty six were interviewed by telephone, and twenty-two were lost to follow-up. Of the eighty-nine patients (124 incisions) who returned for follow-up examination at an average of twenty-five months (range, six to seventy-seven months), eighty-five (96 per cent) were pleased with the result of the plantar incision. None of these patients had altered their activities, and only three had modified their selection of footwear. Of the twenty-six patients who were interviewed by telephone, twenty-five (96 per cent) were pleased with the result. Thus, 110 (96 per cent) of 115 patients (150 plantar incisions) were satisfied with the result. The plantar incision may be used for resection of an interdigital neuroma (primary or recurrent); drainage of an abscess; removal of a foreign body; sesamoidectomy; lateral release of the first metatarsophalangeal joint; or excision of an invaginated keratotic plug (intractable plantar keratosis), a metatarsal head, the plantar aspect of a metatarsal head, or an intermetatarsal bursa. PMID- 8501090 TI - Comparison of tibiofemoral joint forces during open-kinetic-chain and closed kinetic-chain exercises. AB - The purpose of this study was to analyze forces at the tibiofemoral joint during open and closed-kinetic-chain exercises. Five healthy subjects performed maximum isometric contractions at 30, 60, and 90 degrees of knee flexion during open kinetic-chain extension, open-kinetic-chain flexion, and closed-kinetic-chain exercises. Electromyographic activity of the quadriceps and hamstrings, as well as load and torque-cell data, were recorded. Tibiofemoral shear and compression forces were calculated with use of a two-dimensional biomechanical model. The results showed that, during the open-kinetic-chain extension exercise, maximum posterior shear forces (the resisting forces to anterior drawer) of 285 +/- 120 newtons (mean and standard deviation) occurred at 30 degrees of knee flexion and maximum anterior shear forces (the resisting forces to posterior drawer) of 1780 +/- 699 newtons occurred at 90 degrees of knee flexion. The closed-kinetic-chain exercise produced significantly less posterior shear force at all angles when compared with the open-kinetic-chain extension exercise. In addition, the closed kinetic-chain exercise produced significantly less anterior shear force at all angles except 30 degrees when compared with the open-kinetic-chain flexion exercise (p < 0.05). Analysis of tibiofemoral compression forces and electromyographic recruitment patterns revealed that the closed-kinetic-chain exercise produced significantly greater compression forces and increased muscular co-contraction at the same angles at which the open-kinetic-chain exercises produced maximum shear forces and minimum muscular co-contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501091 TI - Total hip replacement without cement for non-inflammatory osteoarthrosis in patients who are less than forty-five years old. AB - Forty-two patients (forty-four hips) who, at an age of less than forty-five years, had a total hip replacement without cement for the treatment of non inflammatory osteoarthrosis, were followed for three to seven years (average, four and one-half years). At the latest follow-up evaluation, thirty-seven hips (84 per cent) had an excellent Harris rating; three (7 per cent), good; one (2 per cent), fair; and three (7 per cent), poor. The mean Harris hip score was 92 points, compared with 43 points before the operation. Two hips (5 per cent) had a revision due to complications. In another hip, there was a progressive radiolucent line around the femoral component, increased shedding of beads, and a low score for fixation and stability, according to the criteria of Engh et al. We concluded that total hip arthroplasty without cement, at least for the time period studied, has a high rate of success for the management of patients less than forty-five years old who have non-inflammatory osteoarthrosis of the hip. PMID- 8501092 TI - The association of age, race, and sex with the location of proximal femoral fractures in the elderly. AB - A retrospective study of the data on 27,370 hospital discharges of patients who had been admitted to non-federal Maryland hospitals from 1979 through 1988 for a fracture of the proximal part of the femur and who had been at least sixty-five years old at the time of the fracture showed that the ratio of trochanteric fractures to fractures of the femoral neck increased linearly with age in white and black women. For men, this ratio was stable across age-intervals, being slightly more than one in white men and less than one in black men. Black patients who had a fracture of the hip were more likely than white patients to have a subtrochanteric, open, or femoral neck fracture. The rate of occurrence of fractures of the hip was highest in white women; the rate decreased successively in white men, black women, and black men. The higher over-all rate of fractures of the hip in white patients was disproportionately influenced by the much higher rate of trochanteric fractures in these patients. PMID- 8501093 TI - Cauda equina syndrome occurring nine years after a gunshot injury to the spine. A case report. PMID- 8501094 TI - Recurrent spontaneous hemarthrosis nine years after a total knee arthroplasty. A presentation with pigmented villonodular synovitis. PMID- 8501095 TI - The use of lasers in orthopaedic procedures. PMID- 8501096 TI - The management of fractures with soft-tissue disruptions. PMID- 8501097 TI - Frederic W. Rhinelander, M.D. 1906-1990. PMID- 8501098 TI - The effects of burn blister fluid on keratinocyte replication and differentiation. AB - The optimal clinical care of burn blisters has not been determined. The effects of burn blister fluid and control serum on epidermal cell proliferation and differentiation were determined. Both burn blister fluid and serum decreased the cell responses necessary for healing of the burn wound by approximately 40%. The degree of suppression varied from 81% to 28% dependency on the specific burn blister fluid and cell tested. These data suggest that reepithelialization may be inhibited beneath burn blisters. We conclude that in most cases burn blisters should be debrided. PMID- 8501099 TI - Cytotoxicity to human leukocytes by topical antimicrobial agents used for burn care. AB - We tested two topical antimicrobial agents (TAAs), silver sulfadiazine and mafenide acetate, to determine their cytotoxic effects when human lymphocytes and neutrophils were incubated with the agents in vitro for 30 minutes. Dilute concentrations of both TAAs markedly inhibited neutrophil respiratory burst activity and mitogen-stimulated lymphocyte proliferation (p < 0.05). The components of silver sulfadiazine (silver and sulfadiazine) were separately tested, and each component inhibited both neutrophil and lymphocyte functions. Mafenide acetate markedly decreased intracellular Ca+2 flux in lymphocytes. The effects of the TAAs were partially reversed when cells were washed and resuspended in medium after they were exposed in vitro to the TAAs. Commonly used TAAs may contribute to local immune dysfunction in the patient with burns. Because evidence suggests that T lymphocytes may participate in wound healing, prolonged treatment with TAAs may also effect certain aspects of wound healing. PMID- 8501100 TI - The inhibition of fibroblast proliferation by a novel monokine: an in vitro and in vivo study. AB - We have identified a product of rabbit macrophages that inhibits fibroblast proliferation. Tested in vitro against several fibroblast populations, this monokine inhibited rabbit conjunctival fibroblast proliferation by 85% (p = 0.005), human conjunctival fibroblast proliferation by 88% (p = 0.005), human hypertrophic scar fibroblast proliferation by 85% (p = 0.005), and human keloid fibroblast proliferation by 79% (p = 0.005). Additionally (in an in vivo model), this monokine was injected into healing rabbit wounds and inhibited fibroblast proliferation by 33% after 7 days (p = 0.0001) and by 27% after 2 weeks (p < 0.0001). Preliminary analysis of the active factor demonstrates that it is not species-specific, has a molecular weight less than 3000 d, is resistant to degradation by trypsin and carboxypeptidase A, is heat-stable, and is produced by macrophages largely in the first 3 days of culture. PMID- 8501101 TI - Keratinocyte allografts accelerate healing of split-thickness donor sites: applications for improved treatment of burns. AB - Grafting with split-thickness autograft skin remains the most effective method for treating burn wounds. When insufficient donor sites are present, decreasing the time required for healing of available donor sites permits more frequent reharvests to continue the grafting process. Cultured human keratinocytes speed wound healing by providing cover and by producing growth factors and extracellular matrix proteins. In this study we compare the rates of healing induced by allografts of cultured keratinocytes applied to split-thickness donor sites with healing by a standard treatment. Sheets of cultured human keratinocytes derived from neonatal foreskins are applied to a portion of a split thickness donor site while the remainder is covered with a temporary skin substitute. The wound is inspected at 5, 7, 9, 11, 14, 17, 20, and 23 days. Biopsies are obtained at 7 days for light and electron microscopy. In 10 patients the average time to healing for sites covered with keratinocytes was 6.6 +/- 1.96 days compared with 12.6 +/- 4.32 days for control sites (p < 0.002). By day 7 most keratinocyte-covered sites showed reepithelization with the formation of a basement membrane and hemidesmosomes at the dermal-epidermal junction. Control areas were unhealed without epithelial coverage. The reepithelized donor sites from three patients treated with cultured keratinocytes were reharvested. In each case these grafts took, and they were equivalent to skin used from donor sites harvested for the first time. Keratinocyte allografts speed healing of split thickness donor sites, thereby increasing the availability of autograft skin for burn wound coverage. PMID- 8501102 TI - Acute adrenal insufficiency in the patient with burns. AB - Acute adrenal insufficiency is an uncommon but devastating complication of severe burn injury. The diagnosis is rarely made antemortem. Acute, fatal, adrenal insufficiency developed in three patients among 807 critically ill patients with burns treated at this institution during the past 6 years. Thermal injuries elevate corticosteroid secretion for weeks after injury, severely stressing the adrenal glands. Overload of the hypothalamic-pituitary-adrenal axis is thought to make this system unusually vulnerable to acute infarction. Although the actual mechanism of adrenal hemorrhage is not clear, the combination of excessive adrenocorticotropic hormone stimulation and hemodynamic instability have been implicated in its evolution. Survival may be too short for characteristic Addisonian metabolic changes to develop. Acute adrenal insufficiency is a rare event that is historically associated with meningococcemia, although any life threatening illness may precipitate this catastrophe. Therefore, when a sudden deterioration in the patient with thermal injuries is encountered, adrenal insufficiency must be considered. PMID- 8501103 TI - Five percent mafenide acetate solution in the treatment of thermal injuries. AB - A 5% mafenide acetate solution was used in the treatment of 669 patients with thermal injuries. This solution was used as the initial topical antibacterial agent in the treatment of the acute burn wound in 276 patients. It was initiated during the intermediate and chronic phases of burn wound therapy in 393 patients. Acid-base derangements did not occur. Discontinuation of therapy because of the patient's pain was necessary in fewer than 1% (17 of 669) of all patients treated. The incidence of rash and pruritus was extremely low. Effective antibacterial activity was achieved. This solution appears to be an effective, safe, and versatile antibacterial agent that produces minimal side effects and is useful in all phases of burn wound management. PMID- 8501104 TI - Methicillin-resistant Staphylococcus aureus eradication in a burn center. AB - Methicillin-Resistant Staphylococcus aureus and its detection, virulence, and significance relative to morbidity, epidemics, and cost have been widely discussed in the literature. Although some experts recommend against attempting to eradicate the organism, our health center decided that under the circumstances this course should be pursued. This article describes the outbreak of Staphylococcus aureus, the rationale for pursuing its eradication, the measures successful in doing so, and the relative costs involved. PMID- 8501105 TI - Auditory and neuropsychiatric behavior patterns after electrical injury. AB - Major electrical injury causes widespread tissue destruction. Slow and incomplete functional recovery after electrocution-type injury has led clinicians to suspect residual brain damage. One hundred and one consecutive patients who were admitted to the hospital because of electrical injury were studied. Forty-eight had electric-current injury. The other 53 had flash, contact, or arcing burns (electrical injury without passage of current). A primary study cohort of 16 patients with electric-current injury and 18 patients who had electrical injury without passage of current received specialized trauma-based psychiatric treatment, which was coordinated with serial auditory and neurologic studies. This strategy served to highlight discrepancies between preinjury and postinjury performance. Twelve of 16 patients with electric-current injury showed neurobehavioral (organic) dysfunction after 1 year, which implied brain damage; eight showed persistent auditory changes. Four of 18 patients who had electrical injury without passage of current met criteria for post-traumatic stress disorder after 1 year; none had neurobehavioral or auditory dysfunction. These findings indicate that patients with electric-current injury are at risk for permanent auditory dysfunction and brain damage, whereas those with other types of electrical burns are not. PMID- 8501106 TI - Safety and efficacy of debridement under anesthesia in patients with burns. AB - Burn wound debridements requiring blunt or sharp manipulations are extremely painful even when large nonanesthetic doses of morphine are used. In this study we describe the use of debridement while the patient is under anesthesia (DUA) when manipulation of the wound is required. Seventy-one debridements were performed on 46 patients. One patient required additional fluids during the DUA, but no deaths, extensive blood losses, or significant changes in nutrition attributable to the DUA occurred. The mean number of required DUAs was 1.6 per patient compared with 6.0 per patient reported in a previous study from the same burn center that involved standard parenteral analgesic doses of morphine sulfate. Patients were completely anesthetized during the procedure. Therefore, they were free of pain and were amnestic for the experience. We conclude that DUA is a safe, efficacious procedure that permits full relief from the pain usually experienced during a manipulative burn wound debridement. PMID- 8501107 TI - Technical considerations in the selection and performance of walkers. AB - The walker is a mobility aid that provides a portable base of support. People of all ages use different kinds of walkers for a variety of reasons. With the correct walker, many people stroll along at the same pace as their companion. Today, walkers are available in a variety of styles and colors and have numerous accessories. It is the purpose of this article to describe the various types and models of walkers and accessories that are available. Our goal is not to recommend or rate the walkers but to help you find the right walker. The ultimate selection of a walker will depend on a cooperative effort between the physiatrist, physical therapist, and medical equipment supplier. Before you purchase a walker you should test it out to decide if it is the right one for you. The physical therapist who supplies your walker should adjust for your height and should check the physical fit of the equipment. Moreover, the physical therapist should demonstrate the proper gait for walking. During the past few years radical changes have occurred in the design and style of walkers. We expect this trend to continue with more attractive, easier-to-use products to be introduced regularly. If you think that your walker is outdated and is not adapting to your lifestyle, talk with your physiatrist regarding alternatives. Today, walkers are as different as their users. Find the best one for you by taking a test walk in your home and community. PMID- 8501108 TI - Patients with burns are successful in work hardening programs. AB - The W.O.R.K. Center at Tampa General Hospital is a facility accredited by the Commission on Accreditation of Rehabilitation Facilities for work hardening and specializes in assisting injured workers in returning to work. The most successful diagnostic group has been the burn injury population referred from the Tampa Bay Regional Burn Center. Eleven patients with burn injuries with an average total body surface area of 20.7% were referred to the W.O.R.K. Center for evaluation and admission to The Work Hardening Program. Ninety-one percent returned to work after discharge from the program compared with a 60% return-to work rate for the total work hardening population at this facility. The success of the program may be attributed to an early referral process and the emphasis on rehabilitation in treating the patient with burn injuries. Work hardening provides a structured, goal-oriented approach in preparing the patient with burn injuries to reenter the work force. PMID- 8501109 TI - President Clinton's health care strategy. PMID- 8501110 TI - Development of computerized registry for the patient with burns: Part I. PMID- 8501111 TI - Study of hope in patients with critical burn injuries. AB - The purpose of this study was to determine which factors patients with critical burn injuries would identify as affecting their feelings of hope; specific attention was given to the influence of nursing actions on these feelings. The nonprobability purposive sample consisted of nine white male patients who had been admitted to a large burn center in the Southwest. Content analysis technique was used to determine the nursing behaviors that influenced the patients' levels of hope. Hope in this study is viewed as a dynamic process with past, present, and future dimensions. The majority of factors that subjects identified as affecting their levels of hope evolved from the present dimension. This study indicates that factors that affected each subject's level of hope were contingent upon where the patient was in the psychological recovery process that occurs after burn injury. Accordingly, the efficacy of specific nursing actions is contingent upon consideration of these same factors. PMID- 8501112 TI - Does the use of an enteral feeding tube with a pH-sensitive tip facilitate enteral nutrition? AB - Enteral feedings are often used to achieve adequate, cost-effective nutritional support. Placement of feeding tubes is accomplished by either a trained nurse or physician form a nutritional support team. A radiographic examination is required to confirm proper placement. These examinations are expensive and delay initiation of feeding while radiographs are taken and evaluated. A new enteral feeding tube (pH-FT) that incorporates a permanent pH-sensitive tip into a small bore feeding tube has been developed. A detachable meter is used to monitor pH. This study was undertaken to determine if the pH-FT was reliable in determining placement as compared with radiograph interpretation. Twenty inpatients (14 males and six females) with diagnoses including major burn, trauma, and gastrointestinal disease were intubated with the use of pH-FT. Measurement of pH was taken at the time the radiographic examination was done. Reference pHs used include the following: stomach, 1.1 to 2.0; stomach in the presence of antacids/H2 blockers, 3.5 to 5.0; and the duodenal, 6.0 to 7.3. Of the 20 patients studied, there were four in whom the pH assessment indicated stomach placement with 100% radiograph confirmation. Sixteen patients had duodenal placement indicated by pH assessment, with radiograph confirmation in 88% (14) of the patients. Two patients had a pH indicating duodenal placement, and radiographic examination showed placement to the pH-FT in the stomach. Two benefits of the pH-FT would be decreased cost and earlier initiation of enteral feeding when the radiographic examination and interpretation are eliminated. PMID- 8501113 TI - Thermal injuries caused by ignition of volatile substances by gas water heaters. AB - Based on the cumulative data of this tertiary care facility over the past 25 years, one out of every 70 pediatric patients admitted to our institution sustained their injuries during an explosive event instigated by the ignition of volatile substances from gas water heaters. The majority of injuries related to gas water heaters can be prevented by decreasing the temperature setpoint of the heater, by protecting the heater element itself, and by elevating the water heater to 18 inches above the floor. The first two issues have been adequately addressed; however, gas-fueled water heaters continue to be installed at floor level. Current national guidelines are too rigid and do not adequately address water-heater installation in private residences. Although general prevention campaigns target appropriate storage of volatile substances, they rarely address the explosive potential of gas water heaters in combination with combustible fumes. PMID- 8501114 TI - Sexual health promotion of the patient with burns. AB - An extensive literature review reveals that the sexuality concerns of patients with burns are rarely a focus. The author introduces the initiation of the PLISSIT (permission, limited information, specific suggestions, intensive therapy) model in the sexual health promotion of the patient with burns. Human sexuality is a profound facet of the total personality. Sexuality encompasses much more than sexual activity or functioning. This article focuses on the resultant impact of burn injuries on the patients' sexuality concerns and expressions, from admission through rehabilitation, with appropriate intervention for sexual health promotion. PMID- 8501115 TI - Time-resolved electron microscopic analysis of the behavior of myosin heads on actin filaments after photolysis of caged ATP. AB - The interaction between myosin subfragment 1 (S1) and actin filaments after the photolysis of P3-1-(2-nitrophenyl)ethyl ester of ATP (caged ATP) was analyzed with a newly developed freezing system using liquid helium. Actin and S1 (100 microM each) formed a ropelike double-helix characteristic of rigor in the presence of 5 mM caged ATP at room temperature. At 15 ms after photolysis, the ropelike double helix was partially disintegrated. The number of S1 attached to actin filaments gradually decreased up to 35 ms after photolysis, and no more changes were detected from 35 to 200 ms. After depletion of ATP, the ropelike double helix was reformed. Taking recent analyses of actomyosin kinetics into consideration, we concluded that most S1 observed on actin filaments at 35-200 ms are so called "weakly bound S1" (S1.ATP or S1.ADP.Pi) and that the weakly bound S1 under a rapid association-dissociation equilibrium with actin filaments can be captured by electron microscopy by means of our newly developed freezing system. This enabled us to directly compare the conformation of weakly and strongly bound S1. Within the resolution of deep-etch replica technique, there were no significant conformational differences between weakly and strongly bound S1, and neither types of S1 showed any positive cooperativity in their binding to actin filaments. Close comparison revealed that the weakly and strongly bound S1 have different angles of attachment to actin filaments. As compared to strongly bound S1, weakly bound S1 showed a significantly broader distribution of attachment angles. These results are discussed with special reference to the molecular mechanism of acto-myosin interaction in the presence of ATP. PMID- 8501116 TI - Purification and properties of transgelin: a transformation and shape change sensitive actin-gelling protein. AB - We have purified the transformation and shape change sensitive isoform of an actin associated polypeptide doublet previously described by us (Shapland, C., P. Lowings, and D. Lawson. 1988. J. Cell Biol. 107:153-161) and have shown that it is evolutionarily conserved as far back as yeast. The purified protein: (a) binds directly to actin filaments at a ratio of 1:6 actin monomers, with a binding constant (Ka) of approximately 7.5 x 10(5) M-1; and (b) causes actin filament gelation within 2 min. Although these activities are controlled by ionic strength (and may be mediated by positively charged amino acid residues) the molecule remains as a monomer irrespective of ionic conditions. EM reveals that the addition of this protein to actin filaments converts them from a loose, random distribution into a tangled, cross-linked meshwork within 1 min, and discrete tightly aggregated foci after 10 min. By use of an "add-back" cell permeabilization system we can rebind this molecule specifically to actin filaments in cells from which it has previously been removed. Since the protein is transformation sensitive and gels actin, we have named it transgelin. PMID- 8501117 TI - Fluorescence anisotropy imaging microscopy maps calmodulin binding during cellular contraction and locomotion. AB - Calmodulin is a calcium transducer that activates key regulatory and structural proteins through calcium-induced binding to the target proteins. A fluorescent analog of calmodulin in conjunction with ratio imaging, relative to a volume indicator, has demonstrated that calmodulin is uniformly distributed in serum deprived fibroblasts and there is no immediate change in the distribution upon stimulation with complete serum. The same fluorescent analog of calmodulin together with steady state fluorescence anisotropy imaging microscopy has been used to define the temporal and spatial changes in calmodulin binding to cellular targets during stimulation of serum-deprived fibroblasts and in polarized fibroblasts during wound healing. In serum-deprived fibroblasts, which exhibit a low free calcium ion concentration, a majority of the fluorescent analog of calmodulin remained unbound (fraction bound, fB < 10%). However, upon stimulation of the serum-deprived cells with complete serum, calmodulin binding (maximum fB approximately 95%) was directly correlated with the time course of the elevation and decline of the free calcium ion concentration, while the contraction of stress fibers continued for an hour or more. Calmodulin binding was also elevated in the leading lamellae of fibroblasts (maximum FB approximately 50%) during the lamellar contraction phase of wound healing and was spatially correlated with the contraction of transverse fibers containing myosin II. Highly polarized and motile fibroblasts exhibited the highest anisotropy (calmodulin binding) in the retracting tails and in association with contracting transverse fibers in the cortex of the cell. These results suggest that local activation of myosin II based contractions involves the local binding of calmodulin to target proteins. The results also demonstrate a powerful yet simple mode of light microscopy that will be valuable for mapping molecular binding of suitably labeled macromolecules in living cells. PMID- 8501118 TI - Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein. AB - The cadherin cell adhesion system plays a central role in cell-cell adhesion in vertebrates, but its homologues are not identified in the invertebrate. alpha Catenins are a group of proteins associated with cadherins, and this association is crucial for the cadherins' function. Here, we report the cloning of a Drosophila alpha-catenin gene by low stringent hybridization with a mouse alpha E catenin probe. Isolated cDNAs encoded a 110-kD protein with 60% identity to mouse alpha E-catenin, and this protein was termed D alpha-catenin. The gene of this protein was located at the chromosome band 80B. Immunostaining analysis using a mAb to D alpha-catenin revealed that it was localized to cell-cell contact sites, expressed throughout development and present in a wide variety of tissues. When this protein was immunoprecipitated from detergent extracts of Drosophila embryos or cell lines, several proteins co-precipitated. These included the armadillo product which was known to be a Drosophila homologue of beta-catenin, another cadherin-associated protein in vertebrates, and a 150-kD glycoprotein. These results strongly suggest that Drosophila has a cell adhesion machinery homologous to the vertebrate cadherin-catenin system. PMID- 8501119 TI - Epiligrin, a component of epithelial basement membranes, is an adhesive ligand for alpha 3 beta 1 positive T lymphocytes. AB - The cutaneous T cell lymphomas (CTCL), typified by mycosis fungoides, and several chronic T cell mediated dermatoses are characterized by the migration of T lymphocytes into the epidermis (epidermotropism). Alternatively, other types of cutaneous inflammation (malignant cutaneous B cell lymphoma, CBCL, or lymphocytoma cutis, non-malignant T or B cell type) do not show evidence of epidermotropism. This suggests that certain T lymphocyte subpopulations are able to interact with and penetrate the epidermal basement membrane. We show here that T lymphocytes derived from patients with CTCL (HUT 78 or HUT 102 cells), adhere to the detergent-insoluble extracellular matrix prepared from cultured basal keratinocytes (HFK ECM). HUT cell adhesion to HFK ECM was inhibitable with monoclonal antibodies (mAbs) directed to the alpha 3 (P1B5) or beta 1 (P4C10) integrin receptors, and could be up-regulated by an activating anti-beta 1 mAb (P4G11). An inhibitory mAb, P3H9-2, raised against keratinocytes identified epiligrin as the ligand for alpha 3 beta 1 positive T cells in HFK ECM. Interestingly, two lymphocyte populations could be clearly distinguished relative to expression of alpha 3 beta 1 by flow cytometry analysis. Lymphokine activated killer cells, alloreactive cytotoxic T cells and T cells derived from patients with CTCL expressed high levels of alpha 3 beta 1 (alpha 3 beta 1high). Non adherent peripheral blood mononuclear cells, acute T or B lymphocytic leukemias, or non-cutaneous T or B lymphocyte cell lines expressed low levels of alpha 3 beta 1 (alpha 3 beta 1low). Resting PBL or alpha 3 beta 1low T or B cell lines did not adhere to HFK ECM or purified epiligrin. However, adhesion to epiligrin could be up-regulated by mAbs which activate the beta 1 subunit indicating that alpha 3 beta 1 activity is a function of expression and affinity. In skin derived from patients with graft-vs.-host (GVH) disease, experimentally induced delayed hypersensitivity reactions, and CTCL, the infiltrating T cells could be stained with mAbs to alpha 3 or beta 1 and were localized in close proximity to the epiligrin-containing basement membrane. Infiltrating lymphocytes in malignant cutaneous B disease (CBCL) did not express alpha 3 beta 1 by immunohistochemical techniques and did not associate with the epidermal basement membrane. The present findings clearly define a function for alpha 3 beta 1 in T cells and strongly suggest that alpha 3 beta 1 interaction with epiligrin may be involved in the pathogenesis of cutaneous inflammation. PMID- 8501120 TI - Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix. AB - PDGF is a powerful mitogen initially identified within platelets, but also shown to be produced by a wide variety of cell types. PDGF is encoded on two separate genes. These give rise to three polypeptides, PDGF B and two forms of PDGF A (SA and LA), resulting from alternative splicing of the PDGF A gene primary transcript. We report that in CHO cells transfected with PDGF gene constructs and producing moderate levels of PDGF homodimers, much of the PDGF LA and B produced, but little if any SA, is found in the matrix laid down beneath the cells. Immunoreactive PDGF in cells, and in matrix below expressing cells, was visualized by laser confocal microscopy. Western blotting of protein in matrix extracts, cell extracts, and secreted into the growth medium was used to demonstrate that the range of PDGF A polypeptides seen in the matrix was overlapping with those reported previously to be cell associated in cell types such as NIH3T3 and COS 7. This suggests that attachment to matrix or cell surface may be alternative fates for these polypeptides, with fate dependent on the characteristics of the producing cells. Immunoreactive PDGF A and B could be partially released by incubation of matrix material with heparin but not with other glycosaminoglycans. Digestion of matrix with chondroitin ABC lyase but not heparitinase or collagenase displaced some PDGF from its attachment sites. The results indicate attachment of PDGF to matrix proteoglycans, at least partly through the glycosaminoglycan moieties, and perhaps to additional components. The significance of matrix deposition for PDGF action is discussed. PMID- 8501121 TI - Fibronectin binding site in type I collagen regulates fibronectin fibril formation. AB - Mov13 fibroblasts, which do not express endogenous alpha 1(I) collagen chains due to a retroviral insertion, were used to study the role of type I collagen in the process of fibronectin fibrillogenesis. While Mov13 cells produced a sparse matrix containing short fibronectin fibrils, transfection with a wild type pro alpha 1(I) collagen gene resulted in the production of an extensive matrix containing fibronectin fibrils of normal length. To study the amino acids involved in the fibronectin-collagen interaction, mutations were introduced into the known fibronectin binding region of the pro alpha 1(I) collagen gene. Substitution of Gln and Ala at positions 774 and 777 of the alpha 1(I) chain for Pro resulted in the formation of short fibronectin fibrils similar to what was observed in untransfected Mov13 cells. Type I collagen carrying these substitutions bound weakly to fibronectin-sepharose and could be eluted off with 1 M urea. The effect of this mutation on fibronectin fibrillogenesis could be rescued by adding either type I collagen or a peptide fragment (CB.7) which contained the wild type fibronectin binding region of the alpha 1(I) chain to the cell culture. These results suggest that fibronectin fibrillogenesis in tissue culture is dependent on type I collagen synthesis, and define an important role for the fibronectin binding site in this process. PMID- 8501122 TI - Multiple negative elements in a gene that codes for an extracellular matrix protein, collagen X, restrict expression to hypertrophic chondrocytes. AB - During skeletal development, chondrocytes go through several stages of differentiation. The last stage, chondrocyte hypertrophy, occurs in areas of endochondral ossification. Mature hypertrophic chondrocytes differ from immature chondrocytes in that they become postmitotic, increase their cellular volume up to eightfold, and synthesize a unique set of matrix molecules. One such molecule is a short collagenous protein, collagen X. Previous studies have shown that collagen X is not expressed by other cell types and that its specific expression in hypertrophic chondrocytes is controlled by transcriptional mechanisms. To define these mechanisms, plasmid constructs containing the chicken collagen X gene promoter and 5' flanking regions fused to a reporter gene (chloramphenicol acetyl transferase, CAT) were transfected into primary cultures of collagen X expressing and nonexpressing cells. A construct containing a short (558 bp) promoter exhibited high levels of CAT activity in all cell types (fibroblasts, immature, and hypertrophic chondrocytes). Adding a 4.2-kb fragment of 5' flanking DNA to this construct resulted in a dramatic reduction of CAT activity in fibroblasts and immature chondrocytes, but had no effect in hypertrophic chondrocytes. Addition of three subfragments of the 4.2-kb fragment to the initial construct, either individually or in various combinations, showed that all subfragments reduced CAT activity somewhat in non-collagen X-expressing cells, and that their effects were additive. Unrelated DNA had no effect on CAT activity. The results suggest that multiple, diffuse upstream negative regulatory elements act in an additive manner to restrict transcription of the collagen X gene to hypertrophic chondrocytes. PMID- 8501123 TI - Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. AB - Previous work from our laboratories has demonstrated that: (a) the striated collagen fibrils of the corneal stroma are heterotypic structures composed of type V collagen molecules coassembled along with those of type I collagen, (b) the high content of type V collagen within the corneal collagen fibrils is one factor responsible for the small, uniform fibrillar diameter (25 nm) characteristic of this tissue, (c) the completely processed form of type V collagen found within tissues retains a large noncollagenous region, termed the NH2-terminal domain, at the amino end of its alpha 1 chain, and (d) the NH2 terminal domain may contain at least some of the information for the observed regulation of fibril diameters. In the present investigation we have employed polyclonal antibodies against the retained NH2-terminal domain of the alpha 1(V) chain for immunohistochemical studies of embryonic avian corneas and for immunoscreening a chicken cDNA library. When combined with cDNA sequencing and molecular rotary shadowing, these approaches provide information on the molecular structure of the retained NH2-terminal domain as well as how this domain might function in the regulation of fibrillar structure. In immunofluorescence and immunoelectron microscopy analyses, the antibodies against the NH2-terminal domain react with type V molecules present within mature heterotypic fibrils of the corneal stroma. Thus, epitopes within at least a portion of this domain are exposed on the fibril surface. This is in marked contrast to mAbs which we have previously characterized as being directed against epitopes located in the major triple helical domain of the type V molecule. The helical epitopes recognized by these antibodies are antigenically masked on type V molecules that have been assembled into fibrils. Sequencing of the isolated cDNA clones has provided the conceptual amino acid sequence of the entire amino end of the alpha 1(V) procollagen chain. The sequence shows the location of what appear to be potential propeptidase cleavage sites. One of these, if preferentially used during processing of the type V procollagen molecule, can provide an explanation for the retention of the NH2-terminal domain in the completely processed molecule. The sequencing data also suggest that the NH2-terminal domain consists of several regions, providing a structure which fits well with that of the completely processed type V molecule as visualized by rotary shadowing. PMID- 8501124 TI - Early lipid intermediates in glycosyl-phosphatidylinositol anchor assembly are synthesized in the ER and located in the cytoplasmic leaflet of the ER membrane bilayer. AB - Glycosylated phosphoinositides serve as membrane anchors for numerous eukaryotic cell surface glycoproteins. Recent biochemical and genetic studies indicate that the glycolipids are assembled by sequential addition of components (monosaccharides and phosphoethanolamine) to phosphatidylinositol. The biosynthetic steps are presumed to occur in the ER, but formal proof of this is lacking. We describe experiments designed to establish the subcellular location of the initial steps in glycosyl-phosphatidylinositol (GPI) anchor biosynthesis and to define the transmembrane distribution of early biosynthetic lipid intermediates. The experiments were performed with the thymoma cell line BW5147.3. A subcellular fractionation protocol was used to show that early biosynthetic steps in GPI assembly, i.e., synthesis and deacetylation of N acetylglucosaminyl phosphatidylinositol, occur in the ER. GPI biosynthetic intermediates were synthesized by incubating the microsomes with UDP-[3H]GlcNAc, and the transmembrane distribution of the labeled lipids was probed with phosphatidylinositol-specific phospholipase C (PI-PLC). Treatment of the radiolabeled microsomes with PI-PLC showed that > 70% of the N-acetylglucosaminyl phosphatidylinositol and glucosaminyl phosphatidylinositol could be hydrolyzed, indicating that the two lipids were primarily distributed in the cytoplasmic (outer) leaflet of the microsomes. Similar cleavage results were obtained using Streptolysin O-permeabilized thymoma cells. When permeabilized cells were incubated with UDP-[3H]GlcNAc and treated with PI-PLC, approximately 85% of the radiolabeled N-acetylglucosaminyl phosphatidylinositol and glucosaminyl phosphatidylinositol could be cleaved, indicating that they were accessible to the enzyme. The cumulative data indicate that early GPI intermediates are primarily located in the cytoplasmic leaflet of the ER, and are probably synthesized from PI located in the cytoplasmic leaflet and UDP-GlcNAc synthesized in the cytosol. PMID- 8501125 TI - Advances in cellular construction. PMID- 8501126 TI - Utilization of microgravity bioreactors for differentiation of mammalian skeletal tissue. AB - Bioreactor cell and tissue culture vessels can be used to study bone development in a simulated microgravity environment. These vessels will also provide an advantageous, low maintenance culture system on space station Freedom. Although many types of cells and tissues can potentially utilize this system, our particular interest is in developing bone tissue. We have characterized an organ culture system utilizing embryonic mouse pre-metatarsal mesenchyme, documenting morphogenesis and differentiation as cartilage rods are formed, with subsequent terminal chondrocyte differentiation to hypertrophied cells. Further development to form bone tissue is achieved by supplementation of the culture medium. Research using pre-metatarsal tissue, combined with the bioreactor culture hardware, could give insight into the advantages and/or disadvantages of conditions experienced in microgravity. Studies such as these have the potential to enhance understanding of bone development and adult bone physiology, and may help define the processes of bone demineralization experienced in space and in pathological conditions here on earth. PMID- 8501127 TI - Cultivation of cell-polymer cartilage implants in bioreactors. AB - Cartilage implants for potential use in reconstructive or orthopedic surgery can be created by growing isolated cartilage cells (chondrocytes) in vitro on synthetic, biodegradable polymer scaffolds. The scaffolds provide specific three dimensional structures which support cell proliferation and biodegrade in a controlled fashion in parallel to cellular regeneration of cartilaginous tissue. Cartilage implants based on chondrocytes and fibrous polyglycolic acid scaffolds were recently shown to closely resemble normal cartilage histologically as well as with respect to cell density and matrix composition (collagen, glycosaminoglycan) [Freed et al., J Biomed Mater Res 27:11-23, 1993a]. These findings form the basis for developing straightforward procedures to obtain implants for clinical use from small, autologous cartilage specimens without any limitations in terms of availability of donor tissue or implant dimensions. Chondrocyte growth and cartilage matrix regeneration on polymer scaffolds are interdependent and also depend on in vitro tissue culture conditions. Under static culture conditions, cell growth rates are diffusionally limited due to increasing cell mass and decreasing effective implant porosity resulting from cartilage matrix regeneration. Optimization of the in vitro culture environment is thus essential for the cultivation of large, clinically useful cartilage implants. Preliminary studies indicate that major improvements can be achieved using bioreactors that provide efficient mass transfer and controlled shear rates at the cell and implant surfaces. PMID- 8501128 TI - Use of microgravity bioreactors for development of an in vitro rat salivary gland cell culture model. AB - During development, salivary gland (SG) cells both secrete factors which modulate cellular behavior and express specific hormone receptors. Whether SG cell growth is modulated by an autocrine epidermal growth factor (EGF) receptor-mediated signal transduction pathway is not clearly understood. SG tissue is the synthesis site for functionally distinct products including growth factors, digestive enzymes, and homeostasis maintaining factors. Historically, SG cells have proven difficult to grow and may be only maintained as limited three-dimensional ductal type structures in collagen gels or on reconstituted basement membrane gels. A novel approach to establishing primary rat SG cultures is use of microgravity bioreactors originally designed by NASA as low-shear culture systems for predicting cell growth and differentiation in the microgravity environment of space. These completely fluid-filled bioreactors, which are oriented horizontally and rotate, have proven advantageous for Earth-based culture of three-dimensional cell assemblies, tissue-like aggregates, and glandular structures. Use of microgravity bioreactors for establishing in vitro models to investigate steroid mediated secretion of EGF by normal SG cells may also prove useful for the investigation of cancer and other salivary gland disorders. These microgravity bioreactors promise challenging opportunities for future applications in basic and applied cell research. PMID- 8501129 TI - Studies of chondrogenesis in rotating systems. AB - A great deal of energy has been exerted over the years researching methods for regenerating and repairing bone and cartilage. Several techniques, especially bone implants and grafts, show great promise for providing a remedy for many skeletal disorders and chondrodystrophies. The bioreactor (rotating-wall vessel, RWV) is a cell culture system that creates a nurturing environment conducive to cell aggregation. Chondrocyte cultures have been studied as implants for repair and replacement of damaged and missing bone and cartilage since 1965 [Chesterman and Smith, J Bone Joint Surg 50B:184-197, 1965]. The ability to use large, tissue like cartilage aggregates grown in the RWV would be of great clinical significance in treating skeletal disorders. In addition, the RWV may provide a superior method for studying chondrogenesis and chondrogenic mutations. Because the RWV is also reported to simulate many of the conditions of microgravity it is a very useful ground-based tool for studying how cell systems will react to microgravity. PMID- 8501130 TI - Three-dimensional growth and differentiation of ovarian tumor cell line in high aspect rotating-wall vessel: morphologic and embryologic considerations. AB - Cancer of the ovary is the leading cause of death from gynecologic malignancy. To understand better these aggressive tumors, the development of in vitro models to study human ovarian cancer is critical. However, the establishment of long-term cell lines has been difficult, due to the generalized poor survival of patient tumor cells grown in primary culture. Satisfactory culture systems for ovarian tumor cells have therefore been limited. To study cellular interactions involved in the growth and differentiation of these tumors, a cell line was established from a mixed mullerian tumor of the ovary. This cell line, designated LN1, was cultured on microcarrier beads in the high aspect rotating-wall vessel. The tumor cells grown in this vessel readily proliferated without a requirement for cocultivation with a supportive cell layer. Evaluation of cellular morphology by phase contrast light microscopy and scanning electron microscopy revealed the presence of three-dimensional multicellular aggregates consisting of multiple cell-coated beads bridged together, as well as scattered aggregates of LN1 cells proliferating as spheroids free in suspension. In contrast to conventional culture systems, culture in the high aspect rotating-wall vessel facilitated the generation of multiple cell types that could be recovered. These results illustrate the ability of this culture system to provide the biological conditions necessary for pluripotent cell growth. PMID- 8501131 TI - Prospects for use of microgravity-based bioreactors to study three-dimensional host-tumor interactions in human neoplasia. AB - Microgravity offers unique advantages for the cultivation of mammalian tissues because the lack of gravity-induced sedimentation supports three-dimensional growth in batch culture in aqueous medium. Bioreactors that simulate microgravity but operate in unit gravity provide conditions that permit human epithelial cells to grow to densities approaching 10(7) cells/ml on microcarriers in suspension, in masses up to 1 cm in diameter, and under conditions of low shear stress. While useful for many different applications in tissue culture, this culture system is especially useful for the analysis of the microenvironment in which host matrix and cells interact with infiltrating tumor cells. Growth in the microgravity based bioreactor has supported morphological differentiation of human colon carcinoma cells when cultured with normal human stromal cells. Furthermore, these co-cultures produced factors that stimulated goblet cell production in normal colon cells in an in vivo bioassay. Early experiments also suggest that the microgravity environment will not alter the ability of epithelial cells to recognize and associate with each other and with constituents of basement membrane and extracellular matrix. These findings suggest that cells grown in bioreactors that simulate aspects of microgravity or under actual microgravity conditions will produce tissues and substances in sufficient quantity and at high enough concentration to promote characterization of molecules that control differentiation and neoplastic transformation. PMID- 8501132 TI - Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. AB - BHK-21 cells were cultured under various shear stress conditions in an Integrated Rotating-Wall Vessel (IRWV). Shear ranged from 0.5 dyn/cm2 (simulated microgravity) to 0.92 dyn/cm2. Under simulated microgravity conditions, BHK-21 cells complexed into three-dimensional cellular aggregates attaining 6 x 10(6) cells/ml as compared to growth under 0.92 dyn/cm2 conditions. Glucose utilization in simulated microgravity was reduced significantly, and cellular damage at the microcarrier surface was kept to a minimum. Thus, the integrated rotating wall vessel provides a quiescent environment for the culture of mammalian cells. PMID- 8501133 TI - pH sensitivity of epidermal growth factor receptor complexes. AB - The association/dissociation binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture have been measured at 4 degrees C as a function of extracellular pH from pH 5-9. At pH 8, steady-state total binding is maximal. As pH is lowered to 6.5, total binding monotonically decreases dramatically. It changes further only slightly between pH 6.5 and 5 to about 20% of the maximum binding value. Scatchard binding plots at pH 7.5 and above show the commonly observed concave-upward, non-linear curve; as pH is lowered, this plot becomes much more linear, indicating that the "high affinity" bound receptor population is greatly diminished. Application of our ternary complex binding model [Mayo et al., J Biol Chem 264:17838-17844, 1989], which hypothesizes complexation of the EGF-bound receptor with a cell surface interaction molecule, indicates that pH may have some direct effects on ternary complex formation, but the major effect is on EGF-receptor dissociation. PMID- 8501134 TI - A point mutation in the 5' splice region of intron 7 causes a deletion of exon 7 in adenosine deaminase mRNA. AB - An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BAD05 derived from a Japanese patient with severe combined immunodeficiency was characterized. As previously reported, one allele of BAD05 expresses undetectable ADA mRNA, and the other allele produces an aberrant mRNA without exon 7. Genomic ADA DNA of BAD05 spanning from a portion of exon 6 to a portion of exon 8 was amplified by PCR. The amplified fragments were cloned into a vector, and 8 clones were isolated and sequenced. The analytical result showed a single base change of G to A at the invariant 5' GT of intron 7 of ADA gene in one allele of BAD05, which accounts for the elimination of exon 7 during splicing. PMID- 8501135 TI - Binding of tissue-type plasminogen activator to human melanoma cells. AB - We have shown (Bizik et al., Cell Regul 1:895-905, 1990) that tPA can activate plasminogen on the surface of human melanoma cells in the presence of alpha 2 macroglobulin (alpha 2M) secretion. In the present study, we investigated the binding of tPA on the surface of Bowes melanoma cells, selected since they lacked production of PAI-1 and alpha 2M. Elution of tPA from the cell layers indicated that polylysine (5 micrograms/ml) and tranexamic acid (10 mM), an analog of lysine, were the most efficient agents for disrupting the interaction between tPA and cell surface component(s). Using a panel of monoclonal antibodies against individual domains of tPA revealed that an antibody directed to the kringle-2 domain of tPA interfered most significantly with cell-surface plasmin generation. As tPA is a glycoprotein, interactions between the tPA sugar moieties and cell surface were also tested by the use of a series of monosaccharides. N-acetyl-D glucosamine (100 mM) was the most potent sugar to release tPA from melanoma cells, but the results indicated that the oligosaccharides of tPA play only a supportive role in the binding of tPA to the cell surface. Quantitative comparison of the cell surface localized tPA, which was eluted by tranexamic acid, with the total cellular tPA showed that cell surface bound tPA could represent up to 10%. We conclude that tPA interacts with the melanoma cell surface in a similar manner as has been described for binding of tPA to fibrin and to the putative endothelial cell surface receptor. PMID- 8501136 TI - Binding and subcellular distribution of cyclosporine in human fibroblasts. AB - The uptake, binding, and subcellular sites of accumulation of [3H]-cyclosporine (CS) in two human gingival fibroblast strains, GN 23 and GN 54, have been examined. GN 23 responds to CS treatment with a decrease in collagenolysis, while GN 54 does not. Binding of the drug was determined using [3H]-CS concentrations ranging from 10(-5) to 10(-8) M in the absence or presence of excess unlabeled CS (1 mM). The binding of the drug to both strains was specific and reached a plateau within 10 min, remaining at that level for up to 1 h. Scatchard analysis of the specific binding of [3H]-CS to the responsive GN 23 strain revealed two dissociation constants: KD = 5 x 10(-8) M (1.2 x 10(7) sites/cell) and KD = 1.4 x 10(-6) M (2.2 x 10(8) sites/cell). GN 54, on the other hand, had only one class of low affinity binding site (KD = 0.47 x 10(-6) M [1.2 x 10(8) sites/cell]). Unlabeled CS (0.01-1 mM) inhibited the binding of [3H]-CS in a dose-dependent manner to both strains, as did the calmodulin antagonist W-7, to a lesser extent. However, W-7 inhibited CS binding much more efficiently in GN 54 than in GN 23, suggesting that calmodulin may be the predominant CS receptor in GN 54. In both strains, 70% of the drug accumulated in the crude nuclear fraction after a 1 min incubation, with very little (< or = 4%) being membrane associated, and the remainder was in the cytosol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501137 TI - Drosophila acidic ribosomal protein rpA2: sequence and characterization. AB - A cDNA encoding the Drosophila melanogaster acidic ribosomal protein rpA2 was cloned and sequenced. rpA2 is homologous to the Artemia salina acidic ribosomal protein eL12'. In situ hybridization to salivary gland polytene chromosomes localizes the rpA2 gene to band 21C. It is a single copy gene, with an mRNA of 0.8 kb. Two-dimensional gel electrophoresis of Drosophila ribosomal proteins followed by immuno-blotting showed that the rpA2 protein has an apparent relative mobility in SDS of 17 kD and an isoelectric point less than pH 5.0. Although the Drosophila gene rp21C may be the same as rpA2, the reported sequences differ. Comparisons of the aligned nucleotide sequences coding for the acidic ribosomal proteins rpA1 and rpA2 of Drosophila with those of other eukaryotes support the view of two separate, though closely related, groups of acidic proteins. Comparison with the Artemia homologues suggests that nucleotide identity may have been conserved by some constraint that acts in addition to the requirement for substantial similarity of amino acid sequences. PMID- 8501138 TI - High mannose type N-linked oligosaccharides on endothelial cells may influence beta 2 integrin mediated neutrophil adherence in vitro. AB - We report herein on the role of N-linked oligosaccharide processing of endothelial cell surface proteins on the adhesion of neutrophils. Monolayers of human umbilical vein endothelial cells were treated for 24 h with deoxymannojirimycin (DMJ), an inhibitor of golgi mannosidase I, which results in changes in glycoprotein processing, and then incubated with neutrophils to examine their ability to adhere to the treated endothelial cells. Treatment with DMJ, which leads to accumulation of high mannose type oligosaccharides, resulted in a twofold increase in adherence of phorbol ester (PMA) activated neutrophils compared to attachment to untreated endothelial cells. This adherence was likely mediated by the beta 2 integrin, Mac-1, and could be specifically inhibited with monoclonal antibodies to ICAM-1 and to the integrin beta 2 subunit. Similarly, IL 1 treatment resulted in a beta 2 integrin mediated increase in neutrophil adherence to the DMJ treated endothelial cells in a dose dependent manner. However, the IL-1 induced adherence was not significantly inhibited by the anti ICM-1 antibody, thus, suggesting the presence of other inducible components on the endothelial cell surface. Our results demonstrate that alterations in glycosylation of N-linked oligosaccharides, resulting in the synthesis of high mannose type sugars on molecules that may interact with the beta 2 integrins, leads to an increased adherence of PMA activated neutrophils to endothelial cells. PMID- 8501139 TI - Enhanced phosphorylation of a 65 kDa protein is associated with rapid induction of stress proteins in 9L rat brain tumor cells. AB - Induction of heat-shock proteins and glucose-regulated proteins in 9L rat brain tumor cells can be differentially elicited by sodium arsenite, cadmium chloride, zinc chloride, copper sulfate, sodium fluoride, and L-azetidine-2-carboxylic acid. The kinds of stress protein induced by the above chemicals varied considerably, mainly determined by the nature and the concentration of the chemicals, as well as the treatment protocols. In addition, at the concentrations where stress proteins can be induced, the above chemicals were able to suppress general protein synthesis and were cytotoxic. Enhanced phosphorylation of a protein with an apparent molecular weight of 65 kDa was detected during the induction of stress proteins except in azetidine treatments during which uptake of phosphate by the cells was impaired after prolonged incubation. The phosphate moiety on the 65 kDa phosphoprotein appeared to be alkaline-stable and two dimensional gel electrophoresis revealed that the phosphoprotein resolved into four isoforms with isoelectric points ranging from 5.1 to 5.6. Enhanced phosphorylation of the same protein was also detected in heat-shocked and withangulatin A-treated 9L cells in which stress proteins were induced. It is suggested that this phosphoprotein may be a common target for heat stress response-stimulated phosphorylation and important in the further metabolic responses of the cell to stress. PMID- 8501140 TI - Clinical review 46: Clinical utility of inhibin measurements. AB - New and specific assays, probably based on two-site assay technology, for various forms of circulating gonadal peptides are likely to be available within the next few years and these in turn should open up a range of potential clinical applications, particularly in andrology, management of ovulatory disorders, and especially ovarian and perhaps other malignancies. Current inhibin assays are already proving to be of great value in ovarian cancer management. The recent demonstration that inhibin subunits and dimeric activin are present in the human adrenal also raises the possibility that measurement of inhibin and activin may ultimately be applicable to the study of adrenal disorders. PMID- 8501141 TI - Prospective use of bisphosphonates in osteoporosis. PMID- 8501142 TI - The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women. AB - The effects of oral alendronate treatment on spinal bone mineral density and biochemical markers of bone turnover were assessed in women in the early postmenopausal period. Sixty-five women were treated with placebo or 5, 20, or 40 mg alendronate daily for 6 weeks in a double blind study. Treatment with alendronate decreased both urinary markers of bone resorption (pyridinolines, hydroxyproline, and calcium) and serum markers of bone formation (osteocalcin and alkaline phosphatase) in a dose-dependent fashion. This short term treatment with alendronate also produced a dose-dependent increase in lumbar bone mineral density measured 7.5 months after the completion of therapy. Median percent changes in integral spinal bone mineral density, as assessed by dual x-ray absorptiometry, were -2.3, -1.2, +0.7, and +1.2 after treatment with placebo and 5, 20, and 40 mg alendronate, respectively. Treatment with alendronate was well tolerated and produced no fever; gastrointestinal intolerance was no more common than with placebo treatment. Short term alendronate treatment in early postmenopausal women decreased bone turnover and increased vertebral density. PMID- 8501143 TI - Activation of the somatotropic axis by testosterone in adult males: evidence for the role of aromatization. AB - To determine whether testosterone modulates the somatotropic axis in adult males, we compared 24-h GH secretion (from 20-min sampling, using Cluster analysis) and insulin-like growth factor-I (IGF-I) levels of five hypogonadal men (aged 20-32 yr) with those of six normal men (aged 21-27 yr), and examined the effects of testosterone replacement (testosterone enanthate 250 mg im monthly). To elucidate whether the action of testosterone on the somatotropic axis is direct, or requires the aromatization of testosterone to estradiol, we also examined the effects of the nonsteroidal antiestrogen, tamoxifen (20 mg/day for 3 weeks), on 24-h GH secretion and IGF-I levels in the normal men and in four of the hypogonadal men during concurrent testosterone treatment. Compared to the normal men, the hypogonadal men had significantly reduced mean GH pulse amplitude (3.1 +/- 0.6 vs. 8.4 +/- 1.7 micrograms/L, P < 0.05), but not pulse frequency. Testosterone treatment resulted in a significant increase in 24-h mean serum GH (0.7 +/- 0.2 to 1.4 +/- 0.2 micrograms/L, P < 0.05), mean GH pulse amplitude (3.1 +/- 0.6 to 5.2 +/- 0.8 micrograms/L, P < 0.01) and serum IGF-I (0.9 +/- 0.1 to 1.1 +/- 0.1 U/mL, P < 0.05). In the normal men, tamoxifen significantly reduced 24-h mean serum GH (1.1 +/- 0.3 to 0.5 +/- 0.1 micrograms/L, P < 0.05), mean GH pulse amplitude (8.4 +/- 1.7 to 4.7 +/- 0.4 micrograms/L, P < 0.05), and serum IGF-I (1.0 +/- 0.1 to 0.7 +/- 0.1 U/mL, P < 0.001). In the hypogonadal men on testosterone replacement, tamoxifen lowered 24-h mean serum GH (1.3 +/- 0.2 to 0.6 +/- 0.2 micrograms/L, P < 0.01), mean GH pulse amplitude (5.5 +/- 1.0 to 2.4 +/- 0.8 micrograms/L, P < 0.01), and serum IGF-I (1.2 +/- 0.1 to 0.8 +/- 0.1 U/mL, P < 0.05). We conclude that testosterone plays an important role in the modulation of the male somatotropic axis in adulthood, as appears to be the case in puberty, and that this effect is partly dependent on the aromatization of testosterone to estradiol. PMID- 8501144 TI - In vivo somatostatin receptor imaging in medullary thyroid carcinoma. AB - Using in vivo scintigraphy with the 111In-labeled somatostatin analog octreotide, tumor localizations were demonstrated in 11 of 17 patients (65%) with medullary thyroid carcinoma (MTC). Tumor localizations in the liver in 7 patients, and in the thyroid in 1 patient were not detected on octreotide scintigraphy, most probably because of normal uptake of labeled octreotide in these organs. Specific somatostatin receptors were demonstrated in vitro on all 5 investigated tumors which had also been visualized in vivo, as well as on 1 tumor that was not. Immunohistochemically, somatostatin was present in 1 of 6 tumors that were visualized in vivo, and in neither of 2 tumors that were not. The ratio of serum calcitonin over carcino-embryonic antigen concentrations was significantly higher in patients whose MTCs were visualized during octreotide scintigraphy than in those whose tumors were not. We have formed the following conclusions: 1) In the majority of patients with metastatic MTC, tumor sites can be visualized using octreotide scintigraphy, although this technique is insensitive in detecting liver metastases or intrathyroidal tumor; 2) The visualization of MTC during in vivo somatostatin receptor imaging correlates with the in vitro presence of somatostatin receptors; 3) The immunohistochemical presence of somatostatin in the tumor does not seem to influence the outcome of in vivo somatostatin receptor imaging; and 4) Higher serum calcitonin over carcino-embryonic antigen ratios in patients whose MTC is visualized during octreotide scintigraphy might imply that somatostatin receptors are present on more differentiated MTC. PMID- 8501145 TI - Acute effects of high fat and high glucose meals on the growth hormone response to exercise. AB - The health promoting, anabolic effects of physical activity may be mediated, in part, by an exercise-associated increase in GH. However, little is known about the acute effects of diet on exercise-induced GH release. We hypothesized that a single meal could attenuate the GH response to exercise by modulating substances like somatostatin, insulin, or glucose. Eleven healthy young adults performed 10 min of high intensity, standardized cycle ergometry in the morning following an overnight fast. On separate days they ingested a noncaloric placebo liquid meal or an isovolemic, isocaloric liquid meal high in either fat or glucose. Venous blood samples were obtained before and for 90 min after exercise began, whereas gas exchange data were measured breath by breath. Peak mean oxygen consumption (VO2) was, on average, 9-fold greater than preexercise levels in all groups. Although there was no difference in preexercise GH levels, mean peak, postexercise GH was 54% lower after the high-fat meal compared with placebo (P < 0.01). Modest decreases in GH response to exercise after the high-glucose meal were not statistically significant. Mean serum somatostatin was significantly higher after the high-fat meal compared with both high glucose and placebo meals. This study demonstrates that exercise-induced GH release can be significantly attenuated by the contents of a single preexercise meal. The high fat meal increased circulating somatostatin and was associated with an inhibition of the GH secretion. The data provide a possible specific mechanism to explain how diet can acutely modulate the anabolic effects of exercise. PMID- 8501146 TI - The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. AB - Plasma low density lipoproteins (LDL) comprise multiple discrete subclasses, differing in size, density, and chemical composition. Gradient gel electrophoresis of LDL has demonstrated three common subclass patterns based on the predominant LDL subclass: large LDL, designated subclass pattern A; small LDL particles, designated subclass pattern B; and an intermediate pattern. Genetic studies have demonstrated that these patterns are inherited, but several lines of evidence suggest that environmental factors are important in the phenotypic expression of the pattern. The LDL B pattern is associated with increased levels of plasma triglyceride, reduced high density lipoprotein (HDL), and obesity. To better define the role of environmental factors on LDL phenotypic expression, we determined LDL patterns in patients with the acquired immunodeficiency syndrome (AIDS), an infection characterized by hypertriglyceridemia and weight loss. Similar to previous studies, plasma triglyceride levels were increased, whereas plasma cholesterol, LDL cholesterol, and HDL cholesterol levels were decreased in the AIDS subjects compared to those in age-matched controls. The percentage of AIDS subjects with the LDL B phenotype was increased 2.5-fold, demonstrating an increased prevalence of the LDL B phenotype in an acquired form of hypertriglyceridemia. For each LDL phenotype in AIDS, serum triglyceride levels were higher than the same phenotypic pattern in controls, with the most marked elevations in triglycerides found in AIDS subjects with the LDL B phenotype. In contrast to what was observed in controls, HDL cholesterol levels were decreased in all AIDS subjects and were unrelated to LDL pattern. Total and LDL cholesterol levels were higher in controls with the LDL B phenotype than in those with the LDL A phenotype, but there was no difference in total and LDL cholesterol in AIDS subjects with LDL B compared to A. On multiple regression analysis in subjects with AIDS, plasma triglyceride levels, age, and HDL cholesterol all contribute to the occurrence of the LDL B phenotype, but elevations in plasma triglyceride levels are the strongest independent predictor. Body mass index was not a predictor of LDL B phenotype in AIDS. These results suggest that disturbances in triglyceride metabolism that are caused by AIDS lead to the appearance of the LDL subclass B phenotype and provide further evidence that environmental or disease states that perturb lipid metabolism can produce an increased prevalence of the LDL B phenotype. PMID- 8501147 TI - Systemic growth hormone does not affect human sleep. AB - Subsequent to sleep onset, GH concentrations increase markedly, suggesting a stimulatory influence of sleep on GH secretion. However, results have been inconsistent as to whether GH conversely exerts a significant influence on sleep. Hence, the effects of exogenous administration of GH and of GH secretion stimulated by GH-releasing hormone (GHRH) on sleep were reexamined in 3 experiments in healthy male volunteers. In Exp I, 12 men participated on 3 experimental nights, receiving a constant iv infusion of 5 IU GH (between 2100 0700 h), an im bolus injection of 5 IU GH at 2100 h, and placebo. In Exp II, the effects of a short iv infusion of a high dose of 48 IU GH (between 2345-2315 h) on sleep were evaluated in 3 men. In Exp III, the effects of continuous infusion of 30 micrograms/h GHRH (between 2200-0700 h) on sleep were compared to the placebo condition in 10 men. Experiments were double blind, within-subject, cross over comparisons and included an adaptation night before experimental nights. On all nights, the subjects went to bed at 2300 h and were awakened at 0700 h. Administration of GH elevated plasma GH and somatomedin-C levels throughout the night (P < 0.005). Neither im administration of 5 IU GH nor iv administration of 5 and 48 IU GH had any effect on the total sleep time or the time spent in different sleep stages during the whole night or in the first and second halves of sleep time. Infusion of GHRH increased nocturnal GH secretion (P < 0.005), but the episodic pattern of GH secretion was maintained. However, sleep remained unchanged during GHRH infusion. From these results we conclude that in healthy man, systemic GH has no physiological role for sleep regulation. PMID- 8501148 TI - A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri. AB - Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed. PMID- 8501149 TI - The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors: structural studies of the TSH-R and the alpha-subunit of Gs in human thyroid neoplasms. AB - The development and progression of thyroid tumors are associated with phenotype specific mutations of genes involved in growth control. Thyroid cell growth is controlled in part by the interaction of TSH with its receptor, with subsequent activation of the GTP-binding protein and its effector, adenylyl cyclase. The resulting increase in intracellular cAMP stimulates growth in thyrocytes. The TSH receptor (TSH-R) is a seven-transmembrane domain receptor. Intracellular domains of the TSH-R important for signal transduction and which may serve as targets for mutational activation have been defined. In addition, mutations at specific loci of the alpha-subunit of G-protein in human thyroid tumors have been described. We examined 92 benign and malignant neoplastic thyroid tissues for possible mutations of the intracytoplasmic domains of the TSH-R known to be involved in signal transduction and for mutations within the hot spots of Gs alpha. Screening was carried out by single strand conformation polymorphism (TSH-R) or denaturing gradient gel electrophoresis (Gs alpha) of polymerase chain reaction-amplified tumor DNA. No mutations were observed in the cytoplasmic domains of the TSH-R, except for a neutral base substitution in codon 460 (GCG [Ala]-->GCA [Ala]) in 3 tumors, which was also present in constitutional DNA from the affected individuals. A heterozygous mutation of codon 201 of Gs alpha (GGT [Arg]-CAT [His]) was observed in a nodule from an adenomatous goiter. In addition, a codon 227 mutation (CAG [Glu]-CAT [His]) was identified in a follicular adenoma. We conclude that mutational activation of the intracytoplasmatic domains of the TSH R is not a significant mechanism of thyroid tumorigenesis, whereas putative activating mutations within exons 8 and 9 of Gs alpha occur infrequently in some benign follicular tumors. PMID- 8501150 TI - Biochemical assessment of bone formation and resorption in acromegaly. AB - The effects of chronic GH and insulin-like growth factor-I (IGF-I) excess on bone metabolism were examined by measuring serum markers of bone formation and urine markers of bone resorption as well as vertebral bone densities in patients with active acromegaly. Fasting serum GH levels were elevated in all 27 patients (31 +/- 11 micrograms/L). Serum calcium levels were within the normal range, except in 3 of 27 (10%) patients with mild hypercalcemia. Urinary calcium excretion, however, was increased in 6 (22%) patients despite mainly normal serum PTH and 1,25-dihydroxyvitamin D levels, suggesting a direct renal GH and/or IGF-I mediated calciuric effect. Urinary hydroxyproline/creatinine excretion was increased in all except 1 patient and correlated with plasma IGF-I levels (r = 0.49; P < 0.02; n = 22). A more specific indicator of bone collagen turnover, urinary type I collagen cross-linked N-telopeptide, was elevated in all except 1 patient and correlated with serum GH (r = 0.47; P < 0.02), IGF-I (r = 0.60; P < 0.005), and urinary hydroxyproline/creatinine excretion (r = 0.62; P < 0.001). Serum bone Gla protein (osteocalcin), a specific marker of osteoblastic activity, was also increased in 50% of the patients and correlated with urinary N telopeptide (r = 0.47; P < 0.02), but not with serum GH or IGF-I concentrations. Trabecular bone density, as determined by quantitative computerized tomography of the lumbar spine, was increased in only 1 patient; 13 others had subnormal bone density. The results suggest that in long-standing acromegaly, osteoblastic and osteoclastic activities are increased. Vertebral trabecular bone mass is usually reduced. Urinary collagen cross-links may serve as a more specific marker of bone resorption in acromegaly. PMID- 8501151 TI - The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men. AB - To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and after treatment with either amlodipine (5 mg) or placebo capsule twice daily for 7 days by determining serum insulin, glucose, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and cortisol in the fasting state and during an oral glucose tolerance test. Amlodipine treatment 1) lowered fasting serum insulin (from 273 +/- 19 to 200 +/- 17 pmol/L; P < 0.0005) and glucose (from 5.4 +/- 0.1 to 5.1 +/- 0.1 mmol/L; P < 0.02), 2) reduced the area under the curve for glucose (from 1342 +/- 25 to 1198 +/- 23 mmol/L.min; P = 0.0001) and the area under the curve for insulin (from 155.5 +/- 7.8 to 103.9 +/- 4.3 nmol/L.min; P = 0.0001) during the oral glucose tolerance test, 3) increased fasting serum DHEA-S (from 5.19 +/- 0.37 to 7.95 +/- 0.58 mumol/L; P = 0.0001) and androstenedione (from 5.65 +/- 0.65 to 6.83 +/- 0.53 nmol/L; P < 0.01), and 4) decreased fasting serum cortisol (from 538 +/- 35 to 494 +/- 26 nmol/L; P < 0.05). Fasting serum androstenedione declined slightly in the placebo group (from 5.96 +/- 0.60 to 5.74 +/- 0.57 nmol/L; P < 0.005), but no change occurred in glucose tolerance, fasting serum DHEA-S, or cortisol. We conclude that amlodipine treatment improves glucose tolerance, reduces fasting and glucose-stimulated serum insulin levels, increases serum DHEA-S and androstenedione levels, and decreases circulating cortisol. PMID- 8501152 TI - Enhanced ovarian steroid secretion before implantation in early human pregnancy. AB - Previous studies have compared ovarian steroid production in the luteal phase of nonconceptive and conceptive cycles. Some investigators reported higher preimplantational levels of progesterone in conceptive cycles vs. nonconceptive cycles, but other studies have found no differences. Many of these results were difficult to interpret because the studies included infertile women and/or women who received exogenous hormones. In this study we have characterized the profiles of gonadotropin secretion and ovarian steroid response during early pregnancy in a population of spontaneously ovulating women and compared them to those in nonconceptive cycles of recently fertile women. Blood samples were collected daily during the luteal phase from 24 women during 51 cycles of artificial insemination with donor semen. Cycles were segregated to those from women who had a successful term pregnancy (normal group) and those having an early spontaneous abortion (SAB group) and were also classified as nonconceptive or conceptive based on measurements of hCG. Serum LH and FSH did not show marked differences between nonconceptive and conceptive cycles in the periimplantation period in either the normal or SAB group. In the normal group, estradiol concentrations were significantly higher in conceptive cycles than in nonconceptive cycles beginning 6 days after the LH peak and continuing through the end of the cycle, while differences in progesterone concentrations bordered on or exceeded significance during the same time period. In the SAB group, preimplantation differences in pituitary gonadotropin and ovarian steroid secretion were not observed, whereas the postimplantation hCG concentrations in the SAB group were significantly lower than those in the normal group. It is reasoned that embryos with defective post-implantation hCG secretion may have had this defect before detection of hCG in serum, thus accounting for the lack of stimulation of steroid secretion in these pregnancies. These findings suggest that the enhanced ovarian steroid secretion in conceptive cycles may be due to a gonadotropic stimulus from the preimplantation embryo. PMID- 8501153 TI - Growth hormone insensitivity associated with elevated circulating growth hormone binding protein in children with Alagille syndrome and short stature. AB - The purpose of this study was to assess GH sensitivity in children with Alagille syndrome (syndromic intrahepatic bile duct paucity) by examining their response to short term administration of recombinant human GH (rhGH). Serum levels of insulin-like growth factor-I (IGF-I) were low despite elevated overnight integrated serum GH concentrations. Administration of rhGH (0.05 mg/kg.day for 3 days) to four growth-retarded children with Alagille syndrome did not significantly alter the serum concentrations of IGF-I and insulin, blood urea nitrogen, or urinary calcium excretion. In contrast, circulating IGF-I increased 2-fold in two children with Alagille syndrome and normal stature. In the control group, consisting of seven prepubertal children with GH deficiency, the predicted changes in response to rhGH in serum concentrations of IGF-I and insulin, urea nitrogen, and urinary calcium excretion were observed. Serum GH-binding protein levels, measured by a ligand-mediated immunofunctional assay, were significantly higher in children with Alagille syndrome than in children with cirrhosis or GH deficiency. We conclude that growth-retarded children with Alagille syndrome are insensitive to GH. The growth disturbances and metabolic defects may be due in part to failure to increase IGF-I concentrations in response to GH, implying that growth-retarded children with Alagille syndrome may benefit from IGF-I treatment. PMID- 8501154 TI - Immunological characterization and immunocytochemical localization of an oviduct specific glycoprotein in the human. AB - The objective of the current study was to generate a polyclonal antibody toward a previously described 110- to 130-kilodalton (kDa) human oviductal glycoprotein and to use the antibody to detect the protein in tissue sections, tissue culture media, and oviductal flushings. The polyclonal antibody was generated in male rabbits against the 110- to 130-kDa glycoprotein partially purified from hydrosalpinx fluid. Segments of human oviducts were either cut into 2- to 3-mm pieces and cultured for 24 h, or fixed and embedded in Araldite for light and electron microscopic immunocytochemistry. The protein was only present in midcycle oviductal flushings and was most evident in culture medium samples obtained at midcycle when analyzed on Western blots. No cross-reactivity was observed with proteins in human serum or human endometrial and cervical explant culture media. Immunoperoxidase staining was observed in the apical granules of the secretory cells lining the oviductal lumen. No staining was noted in other parts of the oviduct or in sections of human endometrium and cervix. Indirect immunogold localization demonstrated specific clustering of gold particles over the apical granules of the secretory cells. In summary, a polyclonal antibody to a 110- to 130-kDa human oviductal glycoprotein was successfully generated. This protein is found in the secretory cells and is released into the oviductal lumen. The synthesis of this protein appears to require elevated levels of estrogen and may play a role in early reproductive events occurring within the oviduct. PMID- 8501155 TI - Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism. AB - The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism. A similar disturbance may occur in secondary hyperparathyroidism, but direct in vivo comparisons of PTH secretion in normal subjects and those with secondary hyperparathyroidism have not been made. Thus, 13 patients with end-stage renal failure and secondary hyperparathyroidism and 20 healthy volunteers underwent dynamic tests of PTH secretion. Changes in ionized calcium were induced by 2-h iv infusions of calcium gluconate or sodium citrate on consecutive days, and the sigmoidal relationship between serum ionized calcium and PTH levels was examined. During sodium citrate infusions, serum ionized calcium levels decreased by 0.21 +/- 0.04 and 0.20 +/- 0.05 mmol/L, respectively (mean +/- SD), in normal volunteers and dialyzed patients (P = NS). Serum PTH levels rose from 27 +/- 7 to 107 +/- 33 pg/mL in controls and from 480 +/- 238 to 859 +/- 412 pg/mL in dialyzed subjects; thus, maximum PTH levels were 396% of preinfusion values in normal subjects, but only 79% greater than baseline values in dialyzed patients (P < 0.001). During the first 30 min of calcium infusions, the increase in serum ionized calcium did not differ between groups, but PTH levels fell more rapidly in normal volunteers; values were 24% of preinfusion levels in controls, but only 56% of the baseline in dialyzed patients (P < 0.01) after 30 min. Minimum PTH levels were attained after 50 min of calcium infusion in normal volunteers and after 70 min in dialyzed patients. The derived values for set-point were 1.21 +/- 0.04 and 1.24 +/- 0.06 mmol/L, respectively, in control and dialyzed subjects (P = NS). These results do not support the contention that the set-point for calcium-regulated PTH secretion is greater than normal in patients with secondary hyperparathyroidism due to end-stage renal disease. PMID- 8501156 TI - Bombesin reduces food intake in lean man by a cholecystokinin-independent mechanism. AB - This double blind study was undertaken to determine whether infusion of bombesin (BBS) inhibits the intake of a carbohydrate-rich meal in nine lean healthy subjects and whether inhibition of food intake by BBS is mediated by cholecystokinin (CCK). During infusion of BBS, the amount of food eaten was decreased compared to that after saline infusion (482 +/- 74 vs. 602 +/- 68 g; P < 0.01). Subjective criteria of satiation were also significantly affected by BBS infusion (P < 0.05). Administration of the CCK receptor antagonist loxiglumide (CR1505) to six of the subjects did not prevent the decrease in food intake due to BBS (365 +/- 69 g) or the subjective criteria for satiety. Furthermore, the amount of food eaten during loxiglumide treatment alone (537 +/- 109 g) was not different from that during control saline infusion. In conclusion, infusion of BBS inhibits the intake of a carbohydrate-rich meal by a CCK-independent mechanism. PMID- 8501157 TI - Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism. AB - Clinical, radiological, histological, and anatomical features in 2 patients with necrotizing infundibulo-hypophysitis are reported. The patients presented with a combination of diabetes insipidus and hypopituitarism. Each was found to have a sellar mass lesion with an abnormally thickened enlarged pituitary stalk that intensively enhanced on contrast magnetic resonance imaging. They were suspected to have pituitary tumors with suprasellar extension. However, tissue obtained at transphenoidal surgery revealed necrosis, fibrosis, and chronic inflammation; there was no evidence of infiltrative, infective, or neoplastic disease processes. Postoperatively, they continued to have diabetes insipidus and hypopituitarism despite radiological improvement and steroid therapy. Several clinical and anatomical features distinguish these 2 cases from classical lymphocytic hypophysitis, the most common entity in the differential diagnosis. Specifically, diabetes insipidus has not been observed preoperatively in 30 cases of lymphocytic hypophysitis, but was present in the 2 cases reported. Histological evidence of tissue necrosis present in these 2 cases is not a feature of lymphocytic hypophysitis. Pituitary stalk involvement on magnetic resonance imaging or computed tomographic scan present in these 2 cases is highly unusual in lymphocytic hypophysitis. Finally, 29 of 30 cases of lymphocytic hypophysitis were females, whereas the 2 cases reported are men. On the basis of these disparate findings, we suggest that these 2 cases represent a unique syndrome, which may be recognized clinically and radiologically. PMID- 8501158 TI - Estimation of daily cortisol production and clearance rates in normal pubertal males by deconvolution analysis. AB - To investigate daily cortisol production and clearance rates in a group (n = 18) of normal unstressed pubertal males, we applied deconvolution analysis to serum cortisol concentrations obtained every 20 min for 24 h. Subject-specific characterization of adrenocortical secretory episodes, cortisol production rate, and serum hormone half-life for nine early pubertal (Tanner I or II; early) and nine late pubertal (Tanner IV or V; late) subjects was undertaken to assess potential roles of sexual maturation and changing gonadal steroid hormone concentrations on glucocorticoid physiology. The estimated cortisol production rate for the early group [16.8 +/- 1.3 mumol/m2 x day (6.1 +/- 0.4 mg/m2 x day)] was indistinguishable from that of the late subjects [14.8 +/- 1.4 mumol/m2 x day (5.3 +/- 0.5 mg/m2 x day)]. No differences were observed between the two pubertal groups in the secretory burst frequency and half-duration, mass of cortisol released per secretory episode, average maximal rate of hormone secretion, and serum cortisol half-life. A significant diurnal pattern of cortisol secretion was observed for all subjects manifest by nyctohemeral variations in the frequency of adrenocortical secretory bursts, the amplitude (maximal rate of cortisol secretion) and the mass of cortisol released per secretory episode. Maximum serum hormone concentrations occurred between 0706 and 1114 h. We conclude that in normal pubertal males: 1) cortisol production rates as estimated by deconvolution analysis are in agreement with other recent independent isotopic estimates, but are lower than many previous estimates; 2) the rise in serum gonadal steroid hormone levels is unassociated with alterations in the production rate or metabolic clearance of cortisol; and 3) increased secretory burst frequency, increased amplitude (maximal rate of cortisol secretion attained within each secretory event), and increased mass of cortisol released per adrenocortical secretory episode give rise to the normal diurnal rhythm of circulating cortisol. PMID- 8501159 TI - Maturational changes of urinary growth hormone excretion in the premature infant. AB - High plasma GH concentrations are observed in the newborn infant. To characterize the maturational change of GH secretion in premature infants, we serially measured 24-h urinary GH excretion in 30 premature infants. The gestational age ranged from 25-37 weeks and birth weight from 468-2415 g. Urinary GH excretion at 1 week of age was negatively correlated with gestational age, birth weight, and length of infants with adequate intrauterine growth. In the infants with 27 weeks of mean gestation (range, 25-28 weeks) mean urinary GH excretion was highest (6.1 micrograms/day) at the first week, decreased to 1.2 micrograms/day by the fourth week, and remained between 0.05 and 0.18 micrograms/day thereafter. When compared to the corresponding conceptional age, there was no postnatal difference in the pattern of GH excretion between infants with 27 and 31 (range, 29-32) weeks of mean gestational age. Persistent hyperexcretion of GH was observed in 4 of the 5 infants with intrauterine or postnatal growth retardation. Our results suggest that the postnatal change of 24-h urinary GH excretion is similar to ontogenic changes of plasma GH in fetus, and GH may have some effects on postnatal growth in premature infants. PMID- 8501160 TI - A prospective randomized trial of antithyroid drug dose in Graves' disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment. AB - Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression). PMID- 8501161 TI - Pituitary volume in men with concurrent heroin and cocaine dependence. AB - Pituitary gland volume was measured in 16 men between the ages of 26-33 with magnetic resonance imaging. Eight male patients had a Diagnostic and Statistical Manual III-Revised, American Psychiatric Association Axis I diagnosis of concurrent opioid and cocaine dependence. The average duration of opioid and cocaine abuse was 7.8 +/- 2.0 and 6.9 +/- 1.4 yr, respectively. All patients were in good physical health as determined by physical examination, blood chemistry, hemogram and hormone analysis, and all tested negatively for the HIV antibody. No patient had any other Diagnostic and Statistical Manual III-Revised Axis I diagnosis or neurological disorder. Eight healthy males served as age-matched control subjects. None of the control subjects had any past or current history of substance abuse or any clinical indication for magnetic resonance imaging. Opioid and cocaine dependent men had significantly larger pituitary gland volumes (730.0 +/- 24.4 mm3) than control subjects (540.0 +/- 26.6 mm3) (P < 0.01). The significant increase in pituitary gland volume in men who abuse opiates and cocaine may be antecedent to detection of abnormal anterior pituitary hormone function. PMID- 8501162 TI - Differential changes in serum concentrations of androgens and estrogens (in relation with cortisol) in postmenopausal women with acute illness. AB - Previous studies of adrenal androgens and estrogens in critical illness were limited by measuring only selected sex steroids and by including men (who have confounding simultaneous changes in gonadal steroids). We evaluated relationships between changes in serum levels of cortisol (F), androgens, estrogens, and gonadotropins in 20 postmenopausal women with acute critical illness to determine if changes in adrenal androgens and estrogens paralleled gonadal axis suppression or adrenal stimulation. Two patterns of changes in sex steroids were observed. Admission serum levels of androstenedione (delta 4-A), estradiol, and estrone, like F, were increased compared to healthy controls (P < 0.0001). delta 4-A and estrone then decreased toward normal by day 5 in parallel with cortisol (r = 0.56 and 0.60). In contrast, admission serum dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) were not elevated and testosterone (T) was decreased in our patients compared to controls (P < 0.0005) in parallel with serum gonadotropin levels. Serum levels of DHEA and T continued to decrease by day 5 in parallel with gonadotropins. We conclude that in agonadal patients with acute critical illness, serum levels of DHEA-S and T are selectively decreased in relation to F, delta 4-A, and estrogens. The decreased serum T levels suggest inhibition of 17 beta-OH-dehydrogenase and/or increased aromatization to estradiol. The marked increase in serum estrogen levels also suggests increased aromatization. The absence of increases in DHEA and DHEA-S suggest enhanced activity of 3 beta hydroxysteroid dehydrogenase and/or inhibition of C17,20-lyase activity of P 450c17. The clinical significance of this marked increase in the ratio of estrogens to androgens in acute illness requires further investigation. PMID- 8501163 TI - Reproductive axis suppression in acute illness is related to disease severity. AB - Changes in the adrenal and thyroid axes in critically ill patients are accentuated by increasing disease severity. However, the relationship of gonadal axis suppression to severity of illness is not well defined. We evaluated serial serum levels of LH, FSH, and testosterone (T) in 59 men and 42 postmenopausal women admitted to critical care units with a spectrum of disease severity. Patients were grouped according to severity of illness by the Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores and by survival. Patients with surgery, renal or hepatic failure, alcohol abuse, endocrine disease, or head trauma were excluded to avoid these confounding factors. In men, mean admission serum T levels in all groups were lower than in healthy controls (P < 0.005). In addition, T levels in men with severe illness (APACHE > 15) were lower than in men with relatively mild (APACHE < 10; P < 0.01) or moderate illness (APACHE 10 15; P < 0.05). These differences were accentuated as hospitalization progressed. In postmenopausal women and men, nadir serum FSH but not LH levels during hospitalization were lower in patients with APACHE greater than 15 than in patients with APACHE scores of 10-15 or less than 15 (P < 0.05). Grouping patients by survival yielded similar results. Analysis of drug effects, age, and PRL did not explain these relationships. We conclude that the degree of both central and peripheral suppression of the reproductive axis in acute illness is related to disease severity. This suppression could not be attributed to other factors known to alter the reproductive axis independently from critical illness (e.g. age, drugs, head trauma, hepatic failure, etc.). These findings further document a general endocrine response to acute illness involving several axes which is graded according to disease severity. PMID- 8501164 TI - Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to Graves' disease in a Caucasian population. AB - Graves' disease (GD) is an autoimmune disease of the thyroid gland. Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition to GD. We have previously reported an increased frequency of HLA DR3/DQ2 in Caucasian patients with GD, and recently the importance of Dw24 encoded by DRB3 gene has been suggested. To further investigate the associations of GD and these genes, 94 unrelated patients with GD and 75 control subjects were typed for HLA-DRB3, -DRB1, -DQA1, and -DQB1, using sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA (PCR SSO). Three findings emerged from these studies. 1) The frequency of subjects positive for DQA1*0501 (GD, 73.4% vs. control 42.7%, P = 0.0001, Pc < 0.001, RR = 3.71) was significantly increased among patients. The frequency of DR3 (GD, 34.0% vs. control 17.3%, P = 0.0146, RR = 2.46), which is in tight linkage disequilibrium with DQA1*0501, was also increased; however, it was not significant when the P value was corrected for the number of antigens tested. Neither DQB1 nor DRB3 alleles were significantly increased in frequency. 2) After exclusion of DR3-positive subjects, DQA1*0501 was still significantly increased (GD, 59.7% vs. control 30.6%, P = 0.0012, Pc < 0.01, RR = 3.35) among patients. 3) The distributions of Dw24 and Dw25,26 (Dw25 or Dw26) did not differ between patients and controls on either DR3 positive or negative groups. These findings suggest that DQA1*0501, or a closely associated unknown gene, confers susceptibility to GD, while Dw24 is not directly involved. The importance of DR3, however, remains to be elucidated, because of the fixed linkage with DQA1*0501. PMID- 8501165 TI - Integrin expression in thyroid cells from normal glands and nodular goiters. AB - To assess the expression of the very late antigens family of the integrin superfamily in normal and diseased thyroid glands, tissue specimens were digested to a single cell suspension and analyzed by flow cytometry with antibodies against the common beta 1 chain and the six alpha chains known to be associated to beta 1. In multinodular goiters, two cell populations were recognized. The thyroglobulin containing follicular cell population, represented the majority of cells; a minor population was composed of leukocytes. In normal glands, more than 97% of follicular cells expressed the beta 1 chain, associated with high levels of alpha 3 and very low levels of alpha 1, alpha 5, and alpha 6. The remaining cells (< 3%) expressed the beta 1 chain with a 10-fold higher intensity, associated with relatively high levels of alpha 1, alpha 5, and alpha 6, in addition to alpha 3. This small subset was much more represented in multinodular goiters, where it ranged from 10-60% of the total follicular cell population. Immunofluorescence on tissue sections showed that very late antigens were mostly located on the basal cell membrane and that in multinodular goiters cells expressing the alpha 1, alpha 5, and alpha 6 chains occurred in clusters. PMID- 8501166 TI - A study of the serum 3,5,3'-triiodothyronine sulfate concentration in normal and hypothyroid fetuses at various gestational stages. AB - We have studied T3 sulfate (T3S) levels, blindly, in coded plasma samples from 21 normal and 3 hypothyroid fetuses at different stages of gestation (19-42 weeks). Fetal plasma samples were obtained by cordocentesis. T3S was detectable in all samples studied, with values ranging from 50-294 (mean +/- SD, 130 +/- 62 pmol/L). Plasma T3S was low (< 45 pmol/L) in all 4 normal adult control subjects studied simultaneously; serum T3S ranged from less than 20 to 130 in another set of 18 control subjects (mean +/- SD, 63 +/- 32 pmol/L). Fetal T3S values were positively correlated with gestational age (r = 0.43; P < 0.05), but not with free T4 (FT4), FT3, or TSH values. In the 3 hypothyroid fetuses at 31, 38, and 40 weeks gestation, respectively, plasma TSH was elevated (26, 98, and 24 mU/L, respectively), FT4 was low (10, 6.7, and 7.5 pmol/L, respectively), and FT3 was normal or high (3.2, 8.2, and 2.2 pmol/L, respectively). However, T3S values in hypothyroid fetuses (88, 133, and 252 pmol/L, respectively) were similar to those in normal fetuses at corresponding gestational ages. We conclude that 1) T3S is detectable in fetal circulation from at least 19 weeks gestation, and its concentration increases with fetal-age; 2) plasma T3S concentrations in the fetus at 19-40 weeks gestation are at least comparable to but generally higher than those in the adult; and 3) plasma T3S levels in hypothyroid fetuses are similar to those in normal fetuses. Recent studies demonstrating the ability of some fetal rat tissues (e.g. cerebral cortex) to desulfate T3S to T3 have suggested a possible role of T3S as a source of T3. Normal T3S in fetal hypothyroidism suggests that T3S may contribute to attenuation of the effects of hypothyroidism during intrauterine life. PMID- 8501167 TI - Selective activation of androgen receptors in the subcortical brain of male cynomolgus macaques by physiological hormone levels and its relationship to androgen-dependent aromatase activity. AB - Aromatase activity (AA) is androgen dependent and independent in subcortical regions of the nonhuman primate brain, but the correlation of androgen receptor (AR) content with AA has not been demonstrated. Thus, we castrated 10 adult male cynomolgus monkeys (Macaca fascicularis) and divided them into 2 groups. One group (n = 6) received empty Silastic capsules, whereas the second group (n = 4) received Silastic capsules filled with testosterone (T). Animals were killed after 3 weeks. Microsomal AA and cytosolic and nuclear AR were determined in specific brain regions dissected from frozen sections. Sera from T-treated subjects contained T, dihydrotestosterone, and LH levels that were not significantly different from the precastration amounts (P < 0.05). Cytosolic AR concentrations declined after T treatment in 12 of 20 brain areas studied (P < 0.05). Nuclear AR levels, on the other hand, were significantly elevated after T treatment (activated) only in the ventral medial nucleus (VMN) and infundibular nucleus/median eminence (P < 0.05). AA distribution was significantly different (P < 0.05) among 20 brain nuclei and subregions. The highest activities were found in the bed nucleus of the stria terminalis, the medial preoptic area, the medial and cortical amygdala, and the VMN. Lesser activities were found in other brain regions. Physiological concentrations of T increased AA only in the VMN and infundibular nucleus-median eminence (P < 0.05). These data suggest that physiological levels of androgens are effective in regulating AA only in those brain areas in which AR are activated. PMID- 8501168 TI - Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. AB - The postpubertal outcome of a group of girls diagnosed of premature pubarche during childhood was assessed 1) to determine the incidence of functional ovarian hyperandrogenism (FOH) through the ovarian-steroidogenic response to the GnRH agonist leuprolide acetate, 2) to validate leuprolide acetate stimulation in FOH diagnosis, and 3) to ascertain whether FOH-predictive biochemical markers exist at the diagnosis of premature pubarche. Of 35 patients (age, 15.4 +/- 1.5 yr), 16 showed hirsutism, oligomenorrhea, and elevated baseline testosterone and/or androstenedione (delta 4-A) levels. Subcutaneous administration of leuprolide acetate (500 micrograms) produced similar increases in gonadotropin levels in oligomenorrheic patients, regularly menstruating patients (n = 19), and controls (n = 12; age, 15.3 +/- 1.3 yr) when tested at 6 h. Of all of the steroids measured, 17-hydroxyprogesterone (17-OHP) and delta 4-A levels 24 h postleuprolide acetate stimulation were significantly higher in oligomenorrheic patients than in the other two groups (P < 0.0001). No overlapping in 17-OHP responses occurred between oligomenorrheic patients and the other groups. Baseline dehydroepiandrosterone sulfate and delta 4-A levels at the diagnosis of premature pubarche correlated with 17-OHP values postleuprolide acetate challenge (r = 0.47; P < 0.005 and r = 0.67; P < 0.0001, respectively). These results show a distinct leuprolide acetate challenge response in 45% of the postpubertal premature pubarche girls studied, suggestive of an increased incidence of FOH, and support the need for continued routine postmenarcheal evaluation of this group of patients. Responses of 17-OHP to leuprolide acetate challenge facilitate the identification of FOH patients, establish this test as a reliable diagnostic tool in FOH diagnosis, and confirm the ovaries as the source of hyperandrogenemia in most patients with androgen excess. Although increased 17-OHP responses after leuprolide acetate stimulation seem to occur more frequently in girls with elevated dehydroepiandrosterone sulfate and/or delta 4-A levels at the diagnosis of premature pubarche, specific biochemical markers predictive of FOH in this group of patients are still lacking. PMID- 8501169 TI - Slow baseline growth and a good response to growth hormone (GH) therapy are related to elevated spontaneous GH pulse frequency in girls with Turner's syndrome. AB - Spontaneous growth and growth responses to GH therapy vary considerably among girls with Turner's syndrome. In an attempt to clarify this variability, we assessed growth parameters, 24-h GH profiles, arginine-stimulated serum GH levels, and plasma insulin-like growth factor-I (IGF-I) concentrations in a group of 41 girls with Turner's syndrome with a mean (+/- SD) age of 13 +/- 3 yr (range, 6.7-18.9). We subsequently treated all girls with biosynthetic GH (24 IU/m2 x week) and documented the growth response after 1 yr of therapy. GH profiles were analyzed according to Pulsar and Cluster, and GH secretion rates were calculated by waveform-independent deconvolution (Pulse). Factor analysis selected the mean 24-h GH secretion rate and number of GH peaks according to Cluster and Pulse as the principal GH profile variables to be used for further analysis. The mean (+/- SD) daily pituitary GH secretion rate was 127 +/- 47 micrograms/L.24 h (range, 37-232). The GH secretion rate correlated inversely with body mass index (r = -0.45; P < 0.01; n = 41). There was no relationship between the GH secretion rate and the growth parameters before or after GH therapy. However, the number of GH peaks (Pulse) correlated negatively with baseline height velocity (r = -0.53; P = 0.03) and was a positive predictor for height velocity increment during the first year of GH therapy (r = 0.71, P = 0.001). The mean (+/- SD) IGF-I level was 217 +/- 91 ng/mL (range, 87-413). There was no relationship between GH secretion rate or growth parameters and IGF-I. However, the number of GH peaks correlated negatively with IGF-I (r = -0.49; P = 0.04; n = 17). We conclude that an elevated spontaneous GH pulse frequency pattern is associated with relatively low IGF-I levels and slow baseline growth in girls with Turner's syndrome and that girls with such a pulse pattern may benefit most from exogenous GH therapy. PMID- 8501170 TI - Bone mineral density in patients with chronic hypoparathyroidism. AB - Photon absorptiometry was used to measure skeletal mass in the proximal femur, lumbar spine, and distal radius in 19 females with hypoparathyroidism after operation for either thyroid carcinoma or hyperparathyroidism. Healthy subjects as well as normocalcemic patients who had undergone the same surgical procedure without developing hypoparathyroidism were used as controls. Skeletal mass was measured after a mean postoperative time of 13 and 10 yr in patients operated on for thyroid carcinoma and hyperparathyroidism, respectively. Bone mass was 10-32% greater in hypoparathyroid patients than in controls. In patients with retained parathyroid function after total thyroidectomy and surgical treatment of hyperparathyroidism, bone mass did not differ from that in age-matched healthy controls. Long term T4 medication in doses that suppressed endogenous TSH production was not associated with a decreased bone mass. Reduced PTH production, vitamin D treatment, and calcium supplementation may all have contributed to the increased bone mass found in the patients with postsurgical hypoparathyroidism. PMID- 8501171 TI - Evidence that fluoride therapy increases trabecular bone density in a peripheral skeletal site. AB - We measured the spinal bone density (SBD) and femoral condyle bone density (FCD) in normal and osteoporotic females (n = 219) both before and during fluoride therapy. SBD and FCD in untreated osteoporotics were significantly lower (P < 0.05) than those in the age-matched controls. SBD and FCD were correlated in the untreated (r = 0.62; P < 0.0001) as well as in the fluoride-treated osteoporotics (r = 0.42; P < 0.0001). SBD and FCD were significantly increased (P < 0.05) in response to fluoride therapy. The average rates of increase in FCD and SBD were similar (1.3 +/- 1.3 vs. 1.24 +/- 1.4 mg/cc.month). We conclude that the osteogenic action of fluoride is not limited to the axial skeleton. An increase in trabecular bone density also occurs at peripheral weight-bearing sites such as the femoral condyle. PMID- 8501172 TI - The development of a radioimmunoassay for reverse triiodothyronine sulfate in human serum and amniotic fluid. AB - Sulfated iodothyronines including T4-sulfate (T4S) and T3-sulfate (T3S) have been identified in human serum and amniotic fluid. Little is known, however, about the existence of sulfate conjugation of reverse T3 (rT3S) in man. In this report, we employed a novel, sensitive, and specific rT3S RIA to address this question. The rabbit antiserum to rT3S was highly specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reaction with the antiserum. Only T4S and T3S cross reacted significantly (0.3% and 0.01%, respectively); other analogs cross-reacted less than 0.0001%. The detection threshold of the RIA was 14 pmol/L (1.0 ng/dL). The mean serum rT3S concentration (pmol/L) was 40 in euthyroid subjects. Values were similar in hypothyroid patients (38) and pregnant women (52) but significantly (P < 0.01) elevated to 176 in hyperthyroid patient, 74 in patients with nonthyroid illnesses, and 684 in cord sera of newborns. Serum rT3S increased significantly in hyperthyroid patients 1 day after administration of 1 g sodium ipodate orally. Reverse T3S was detected consistently in amniotic fluid at 14 to 22 weeks of gestation and showed a marked rise 1-3 weeks after intraamniotic administration of 500-1000 micrograms T4. The various data suggest that: (1) rT3S is a normal component of human serum and amniotic fluid; (2) it is derived from metabolism of T4 or rT3; (3) circulating rT3S increases in hyperthyroidism and in circumstances where type I 5'-monodeiodinating activity is low, e.g. nonthyroid illnesses, fetal life, and after administration of ipodate. PMID- 8501173 TI - Endothelin levels in human amniotic fluid at mid-trimester and at term before and during spontaneous labor. AB - Endothelin (ET)-1 is synthesized in human amnion and immunoreactive (ir) ET is present in amniotic fluid in concentrations 10- to 100-times those found in plasma. ET-1 is a potent uterotonin; therefore, the possibility must be considered that ET-1, derived from amnion/amniotic fluid, serves to promote the uterine contractions of human labor. In term pregnancies, after labor begins, the amniotic fluid normally becomes divided into the upper and forebag compartments as the fetal presenting part is engaged in the maternal pelvis. The forebag tissues are exposed in the vagina because of cervical dilatation. Vaginal fluid contains microorganisms, bacterial toxins, and cytokines, e.g., interleukin-1 beta, that oblige an inflammatory reaction. Increased ET-1 formation in these tissues of the forebag would be indicative that the greater rate of ET-1 formation and entry into amniotic fluid was an aftereffect of labor, not a cause of parturition. The levels of irET in amniotic fluid during the midtrimester of human pregnancy, 93.3 +/- 7.4 pmol/L (mean +/- SEM, n = 38), were significantly greater than those in amniotic fluid at term before the onset of labor, 39.8 +/- 4.1 (n = 33, p < 0.01). The levels of irET in the upper compartment during labor, 45.5 +/- 3.5 pmol/L (n = 40), were not significantly different from those in amniotic fluid before labor, but were significantly less (p < 0.01) than those in amniotic fluid of the forebag, 82.1 +/- 5.2 pmol/L (n = 125). These findings are suggestive that increases in the concentration of ET in amniotic fluid at parturition are confined to the forebag and are the result of ET formation after labor begins. Inflammation of the tissues lining the forebag compartment of the amniotic fluid is a normal consequence of labor. Therefore, the entry of inflammatory response mediators, some of which are uterotonins, viz., ET and prostaglandins, into forebag amniotic fluid is an aftereffect of labor and not indicative of a role for these agents (in amniotic fluid) in the initiation of parturition. In a subset of the amniotic fluids from normal pregnancies at term, prostaglandin (PG) levels also were determined. There was a highly significant correlation between the levels of irET and PGE2 in the forebag compartment (p < 0.0001); there was no correlation between irET and PGE2 levels in the upper compartment or in amniotic fluid collected at term prior to labor onset.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501174 TI - Are failed-fertilized human oocytes useful? PMID- 8501175 TI - Human follicular fluid from pre-ovulatory follicles in patients undergoing in vitro fertilization inhibits the in-vitro growth of gram-positive micro organisms. AB - In this study, we assessed the antibacterial activity of human follicular fluid obtained from patients undergoing oocyte aspiration for in-vitro fertilization and embryo transfer. Gram-positive and Gram-negative microorganisms and Candida albicans were added to the follicular fluid and broth cultures which served as controls. Follicular fluid was shown to be inhibitory against Gram-positive microorganisms; this inhibition was probably due to lysosyme and progesterone. Growth of Gram-negative micro-organisms and C. albicans were, however, supported by follicular fluid incubation. PMID- 8501176 TI - Effects of gonadotrophin-releasing hormone agonists (GnRHa) on follicle and oocyte quality. AB - This review summarizes the main clinical and research studies on direct and indirect effects of gonadotrophin-releasing hormone agonists (GnRHa) on follicles and oocytes in animals and humans. There is evidence for extra-pituitary actions of GnRHa, especially on follicle growth, follicular steroidogenesis, and oocyte meiotic maturation. Different effects have been reported from using various GnRHa molecules. However, a direct effect of GnRHa on oocyte quality in gonadotrophin stimulated cycles has not yet been demonstrated. Observed high pregnancy rates per ovarian puncture in in-vitro fertilization cycles using GnRHa, at least in long protocols, might result from higher numbers of oocytes recovered following administration of large doses of gonadotrophins, despite the fact that these oocytes may have a lower ability to fertilize and grow. Although there are obvious clinical advantages of using GnRHa for ovarian stimulation, more studies are needed to clarify the effects of these treatments at ovarian and uterine levels. PMID- 8501177 TI - Steroid production in cultured thecal cells obtained from human ovarian follicles. AB - During follicular maturation there is a co-ordinated hormonal regulation of the theca and granulosa cells. It is generally believed that granulosa cell proliferation and differentiation are promoted mainly by follicle stimulating hormone (FSH) and that luteinizing hormone (LH) regulates the function of the theca cells. The aim of the present study was to examine the effect of LH/human chorionic gonadotrophin (HCG) on steroid production in human thecal cells. Isolated follicles (5-20 mm) were obtained during the follicular phase of the menstrual cycle in 10 women undergoing gynaecological laparotomy for reasons unrelated to ovarian pathology. The leading follicle(s) was excised and dispersed cells of the theca interna layer were isolated through combined mechanical and enzymatic techniques. The thecal cells were cultured 4-6 days with and without LH/HCG. Medium levels of androstenedione, testosterone and progesterone were measured by radioimmunoassay. Isolated thecal cells, cultured for 6 days, showed a high sensitivity to stimulation by LH/HCG. Steroid secretion was highest during days 0-2 and then declined gradually. LH/HCG stimulated steroid production in a dose-dependent way with the maximal stimulatory effect of LH at a concentration of 1-10 ng/ml, and of HCG at 0.01-0.1 IU/ml. The important question, especially in clinical situations, of the optimal level of LH for normal follicular maturation, remains to be answered. The present study is compatible with the view that thecal cell steroidogenesis in vivo is close to maximally stimulated by normal basal LH levels. PMID- 8501178 TI - Effects of synthetic growth hormone-releasing factor in women treated with gonadotrophin. AB - To evaluate the effects of synthetic growth hormone-releasing factor (GRF) in women with idiopathic infertility who were treated with human menopausal gonadotrophin (HMG), 13 women with this condition were randomly assigned to undergo treatment with HMG-GRF (500 micrograms twice daily) or HMG-placebo. Conception occurred in four of six women (14 cycles) who received HMG-GRF and in one of seven women (22 cycles) who received HMG-placebo. No difference was found in the amount of HMG and the duration of HMG required to induce ovulation between the two groups of patients. The overall serum growth hormone and insulin-like growth factor I concentrations were higher in the GRF than in the placebo group. No difference was found in serum oestradiol or inhibin concentrations between the two groups. Our results suggest that in women with idiopathic infertility, administration of GRF does not decrease the duration or the amount of HMG required to induce ovulation. However, it appears that in this small group concomitant treatment with GRF increases the pregnancy rates in women who are treated with HMG (4/14 cycles compared with 1/22 cycles). PMID- 8501179 TI - An aggressive philosophy in controlled ovarian stimulation cycles increases pregnancy rates. AB - To assess the effect of timing of human chorionic gonadotrophin (HCG) administration in ovarian stimulation cycles, the serum oestradiol concentration and follicle profile were compared with the clinical pregnancy rate in 582 ovarian stimulation-intra-uterine insemination (OS-IUI) cycles and 3917 in-vitro fertilization-embryo transfer (IVF-ET) cycles. The pregnancy rates increased exponentially with increasing oestradiol in both OS-IUI and IVF-ET cycles (R2 = 0.720, P < 0.001) but then decreased in OS-IUI cycles when the oestradiol concentration exceeded 5000 pmol/l (R2 = 0.936, P < 0.004) at HCG administration. In OS-IUI cycles the percentages of cycles with three or more mature follicles (> or = 18 mm diameter) increased up to an oestradiol concentration of 5000 pmol/l then declined, mirroring the pregnancy rate (R2 = 0.900, P = 0.01). The exponential increase in pregnancy rate with increasing oestradiol concentration in IVF-ET cycles suggests that high oestradiol concentration does not have a deleterious effect on endometrial receptivity. The decrease in pregnancy rate in OS-IUI cycles when oestradiol concentration exceeded 5000 pmol/l reflected fewer mature follicles, resulting from premature administration of HCG to avoid severe ovarian hyperstimulation syndrome (OHSS). We recommend that HCG administration be delayed until multiple follicles have reached maturity, and reducing the risk of severe OHSS by converting high risk OS-IUI cycles to IVF-ET, or if funds or facilities are unavailable, transvaginally draining all but four or five mature follicles. PMID- 8501180 TI - Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women. AB - The role of dopamine and opiates in the suckling-induced suppression of gonadotrophin secretion and prolactin release was investigated during lactational amenorrhoea in fully breastfeeding women at 12 weeks post-partum. A total of 26 women, 20 using non-steroidal methods of contraception and six using the progestogen-only pill, Noriday (POP), breastfed their babies on demand at a frequency of 3.6 +/- 0.2 suckling episodes during the 8 h study period while blood samples were collected at 10-min intervals. Five hours after the start of sampling six women were given the dopamine antagonist metoclopramide (10 mg, i.m.) while four women received saline. In a second experiment, six women using nonsteroidal contraception and three women on the POP received an i.v. infusion of the opiate antagonist naloxone (1.6 mg/h) for 2 h, while four women using non steroidal contraception and three women on the POP were infused with saline. Two hours after the i.m. injection or start of infusion all women were given an i.v. injection of 10 micrograms gonadotrophin releasing hormone (GnRH) and samples were collected for a further 1 h. All samples were assayed for luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin. Plasma concentrations of oestradiol were < 60 pmol/l in all women and they remained amenorrhoeic for at least 10 weeks after the study. Pulsatile release of LH was only observed over the 5 h pre-treatment period in 10 of the 20 non-steroid taking women (1-3 pulses/5 h), and in one of the six women (1 pulse/5 h) on POP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501181 TI - Combined oestrogen-progestin treatment of vaginal haemorrhage following gonadotrophin-releasing hormone agonist therapy of uterine myomas. AB - Three pre-menopausal women with uterine myomas were treated with leuprolide acetate depot and experienced profuse vaginal bleeding 7-11 weeks after initiation of treatment, despite profound oestradiol suppression. In each case, leuprolide therapy was discontinued and the women were treated with combination oral contraceptives and ferrous sulphate. Vaginal bleeding ceased within 24-48 h of oral contraceptive treatment in all women. Haemoglobin concentrations were restored to normal values and all women underwent definitive surgical treatments after 4-6 weeks of oral contraceptive treatment without the need for homologous blood transfusion. The final pathology report revealed focal necrosis of submucous myomas in all cases. PMID- 8501182 TI - A case of permanent endometrial hypotrophy after long-term use of oral contraceptives. AB - We report the case of a 32-year-old patient who after 14 years of uninterrupted use of low-dose, combined, oral contraceptive agents presented permanent endometrium damage. The patient was referred for prolonged unexplained infertility with medical history negative for any kind of endometrial trauma or subclinical endometritis. After the suspension of the oral contraceptives the patient showed a particular discrepancy between a prompt recovery of the menstrual cycle and absolute inability to obtain a normal endometrial growth. The poor endometrial response appeared during cycles of ovarian stimulation as well as during cycles of hormone replacement. A review of the literature and theoretical interpretations have been attempted in the discussion. PMID- 8501183 TI - Does contraception modify the risk of endometriosis? AB - Long episodes of regular, prolonged, abundant menstrual flows are generally agreed to increase the risk of endometriosis. Since oral oestrogen-progestogen combinations reduce and intra-uterine contraceptive devices increase menstrual flow, an effect on the risk of development of endometriosis in women utilizing these forms of contraception could be expected. Analysis of the most recent epidemiological observations shows no consensus on a possible relationship between use of cyclic oral contraceptives and endometriosis, with an increase, a decrease, and no effect on the risk of developing the disease all being reported. A lower relative risk of endometriosis in previous users of the intrauterine contraceptive device was only found in two series, most of the other data suggesting a rise in risk or no effect. Further studies on the relationship between type of contraception and endometriosis are needed to demonstrate whether the risk of development of the disease could be influenced, and whether well tolerated, relatively inexpensive, long-term treatment might be available for symptomatic patients not desiring offspring. PMID- 8501184 TI - Anti-nidatory effect of a single, early post-ovulatory administration of mifepristone (RU 486) in the rhesus monkey. AB - The hypothesis that post-coital administration of mifepristone (RU 486) as a single dose in the early luteal phase can be an effective anti-nidatory strategy was tested using the rhesus monkey as the experimental model. Incidence of pregnancy, vaginal bleeding patterns, profiles of menstrual cyclicity and of serum levels of progesterone and oestrogen were examined following administration of RU 486 as a single dose of 10 mg/kg and 2 mg/kg body weight on the second day after ovulation. In control monkeys (group 1; n = 5) receiving the vehicle alone (benzyl benzoate:olive oil, 1:4, v/v) there was a 60% pregnancy rate. Following s.c. administration of RU 486 at both doses, no pregnancy was recorded in a total of 33 treatment cycles in 12 monkeys. Five monkeys received RU 486 at 10 mg/kg s.c. (group 2) in three consecutive cycles. All animals had complete inhibition of implantation; in addition, the treatment cycle length was prolonged (P < 0.001) due to an extension of the luteal phase. The subsequent follicular phase was unaffected. Mild, premature vaginal bleeding during the luteal phase was recorded in five treatment cycles, 3-5 days after drug application. Though the serum profiles of progesterone and oestrogen in these monkeys showed marked individual variations, there was a characteristic progesterone rebound about 18 20 days after drug administration. Monkeys in group 3 were given RU 486 at 2 mg/kg, s.c. either for three consecutive cycles (group 3a; n = 4) or for two consecutive cycles (group 3b; n = 3). Premature luteal phase vaginal bleeding occurred only in four treatment cycles, within 2-6 days post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501185 TI - Cumulative pregnancy rate from one gamete intra-fallopian transfer (GIFT) cycle with cryopreservation of embryos: a practical mathematical calculation. AB - We evaluated the cumulative pregnancy rate from one gamete intra-Fallopian transfer (GIFT) cycle plus subsequent cycles in which embryos cryopreserved at the time of the original GIFT cycle were transferred. All patients who had their first GIFT cycle in our centre between January, 1989 and March, 1991 were included. Ovarian stimulation was accomplished with leuprolide acetate (luteal phase protocol) and a combination of follicle stimulating hormone and human menopausal gonadotrophin. GIFT was performed with three to five oocytes. Excess oocytes were inseminated and good quality embryos were cryopreserved at the 2- to 4-cell stage with 1-2 propanediol. When the GIFT cycle did not result in a pregnancy, uterine transfer of cryopreserved embryos was carried out in subsequent unstimulated cycles. A total of 97 patients had GIFT and 46 pregnancies were achieved (47.4%). A total of 51 patients (52.5%) had embryos frozen; of these, 21 were from the non-pregnant group (41.1%) and 30 from the pregnant group (65.2%) (P < 0.05). Up to now, 22 of them have undergone a frozen thawed embryo transfer cycle, and two of them achieved a pregnancy. Based on these data, patients having a GIFT could theoretically expect a cumulative pregnancy rate of 52.2%. PMID- 8501186 TI - Homologous intra-uterine insemination has no advantage over timed natural intercourse when used in combination with ovulation induction for the treatment of unexplained infertility. AB - The objective was to evaluate the role of homologous intrauterine insemination compared with timed natural intercourse, both combined with ovulation induction, in the management of unexplained infertility. A total of 48 couples presenting at a large teaching hospital infertility clinic with unexplained infertility of at least 3 years duration comprised the main study group, and 36 couples with identical entry criteria but under the care of another clinician made up a parallel control group. A randomized design of treatment cycles with within-group and between-group controls was used. Couples in the main study group were treated with either homologous intra-uterine insemination or timed natural intercourse in gonadotrophin-releasing hormone analogue down-regulated cycles, in which ovulation was induced with human menopausal gonadotrophin and human chorionic gonadotrophin. Alternate cycles were monitored to enable optimum timing of natural intercourse provided within-group controls. Couples in the control group underwent timed homologous intravaginal artificial insemination. Cycle fecundity and pregnancy outcome in treated and control groups were monitored. Cycle fecundity of 0.11 in 85 ovulation-induced cycles was significantly higher than 0.02 in 62 within-group and 0.01 in 103 between-group control cycles. There was no difference in conception rates between homologous intra-uterine insemination and timed natural intercourse cycles with ovulation induction. Of the 11 established pregnancies in the ovulation induced group, nine delivered healthy babies (five singleton, three twin, one triplet) and two were ectopic. Results confirmed the value of active management for couples with long-standing unexplained infertility but failed to demonstrate any advantage of homologous intra-uterine insemination over ovulation induction alone. PMID- 8501187 TI - The efficacy of short-term gonadotrophin-releasing hormone agonists versus human chorionic gonadotrophin to enable oocyte release in gonadotrophin stimulated cycles. AB - One of the reasons for failure to conceive following human menopausal gonadotrophin (HMG) therapy may be due to non-release of oocytes from the follicles. We hypothesized that by using a gonadotrophin-releasing hormone agonist (GnRHa) for a short duration, endogenous release of luteinizing hormone and follicle stimulating hormone may enable oocyte release to occur, similar or superior to the effect of human chorionic gonadotrophin (HCG). This study attempted to compare the efficacy of HCG versus the GnRHa leuprolide acetate to release oocytes and achieve pregnancies and to compare the effectiveness of leuprolide acetate versus a combination of HCG with HMG to release oocytes. Unfortunately due to lack of prior data, many patients preferred to reject leuprolide acetate in favour of HCG, resulting in three times as many patients being treated with HCG in cycle 1; 78.2% of oocytes were released following leuprolide acetate versus only 55.7% with HCG. Interestingly, 87.5% of those females in whom oocyte release failed in cycle 1 with HCG did indeed release with leuprolide acetate in cycle 2, but none of these previous failures released with HCG in cycle 2. Pregnancy rates were equal in those women releasing oocytes, whether treated with HCG or leuprolide acetate. These preliminary data justify a larger randomized study. PMID- 8501188 TI - Chromosome studies in in-vitro fertilization patients. AB - Human fertility problems may be due to chromosomal aberrations in one or both partners. In couples asking for in-vitro fertilization (IVF) the question arises as to whether chromosomal analysis is necessary. We analysed the karyotypes of 72 couples attending our clinic for IVF. Normal chromosomes were found in 131 individuals. One male was found to be a carrier of a Robertsonian translocation t(14q;21q), a second male had a reciprocal translocation t(2;4)(q14;p15) and 11 females exhibited sex chromosome mosaicism. A single cell aberration was demonstrated in 26% (38/144) of all individuals studied. These results clearly show that chromosomal analysis should be performed in couples asking for IVF. PMID- 8501189 TI - Chemical composition and protein source in the capacitation medium significantly affect the ability of human spermatozoa to undergo follicular fluid induced acrosome reaction. AB - We studied the effect of media composition on sperm capacitation, using Biggers Whitten-Whittingham (BWW) medium, Ham's-F10 and a modified Tyrode's medium (HSM) supplemented with bovine serum albumin (BSA) or fetal cord serum (FCS). We evaluated the effect of chemical environment and protein supplementation on the sperm motion parameters of curvilinear velocity and linearity, and on the ability of incubated spermatozoa to undergo follicular fluid induced acrosome reaction. Neither chemical composition nor protein supplementation of capacitation media greatly affected motion parameters after 2 h incubation. Furthermore, chemical composition had only a small effect on the ability of spermatozoa to undergo the acrosome reaction upon exposure to follicular fluid. A higher proportion of spermatozoa underwent acrosome reaction after incubation in HSM (8% control (C); 28% follicular fluid) than in BWW (8% C, 17% follicular fluid) or Ham's F-10 (6% C, 19% follicular fluid). By contrast, protein source proved critical in determining acrosome reaction inducibility. Spermatozoa incubated in BSA supplemented media showed a 4-fold increase in acrosomal discharge when exposed to follicular fluid (6% C, 22% follicular fluid) compared to controls while spermatozoa incubated in FCS were unable to undergo acrosome reaction (6% C, 6% follicular fluid). Simultaneous addition of FCS to BSA capacitation medium blocked acrosome reaction inducibility and the late addition of BSA, after sperm incubation in FCS, did not facilitate acrosome reaction. We propose that an inhibitor of sperm capacitation is present in FCS and therefore, the selection of optimum incubation conditions for spermatozoa may be of critical importance when evaluating or treating infertile patients. PMID- 8501190 TI - Chromosome analysis of human spermatozoa stored in vitro. AB - Two-hundred-sixty-five chromosome spreads from control human sperm samples capacitated in TEST-yolk buffer at 4 degrees C and 232 chromosome spreads from sperm samples incubated in vitro in Biggers-Whitten-Whittingham (BWW) for 24 h at room temperature prior to capacitation, were studied after fusion of sperm cells with zona-free hamster eggs. Sperm cells were provided by two volunteer donors. The results indicate an increase in chromosome structural abnormalities after in vitro incubation of the spermatozoa from 1.8 to 7.7% in donor no. 1 and from 4.5 to 12.5% in donor no. 7. Overall, structural abnormalities increased 3.3-fold. The number of aneuploid spermatozoa and the sex ratio did not change significantly. The implications of the use of different media for storing spermatozoa are discussed. PMID- 8501191 TI - Frequency and predictive value of antisperm antibodies among infertile couples. AB - Although sperm-associated antibody could impair fertility through various mechanisms, the results of follow-up studies do not uniformly confirm that pregnancy rates are lower when one of the infertile partners demonstrates antibody to spermatozoa. We conducted a prospective double-blind cohort comparative analysis in which antibody assay results were not available to physicians or patients for clinical management. The diagnostic protocol included mid-luteal progesterone, semen analysis, hysterosalpingogram and laparoscopy. The serum of each partner was assayed by immunobead testing, tray agglutination testing and a gelatin agglutination test. Data on relevant clinical characteristics and events during follow-up were collected prospectively. Among 471 couples in whom both partners were evaluated, 42 (8.9%) tested positive for anti-sperm antibodies by one or more assays, including 38 (8.1%) male partners and 6 (1.3%) female partners. The number of conceptions was 118/429 (27.5%) in antibody negative couples, 9/38 (23.7%) in male partner-positive couples and 1/6 (16.7%) in female partner-positive couples. With proportional hazards analysis, antibody status in either partner was not a significant independent predictor of time to pregnancy. PMID- 8501192 TI - Improved hatching in mouse embryos brought about by combined partial zona dissection and co-culture. AB - In this study 874 mouse embryos were allocated to six groups including a control, co-culture, and four groups that underwent partial zona dissection (PZD): at the 2-cell (PZD-2) and morula stages (PZD-M) both with and without co-culture. Rates of complete blastocyst hatching on day 5 increased in the following order: control, co-culture alone, PZD-2 alone, PZD-M alone, PZD-2 with co-culture and PZD-M with co-culture (P < 0.00001). PZD-M led to significantly higher rates of complete blastocyst hatching compared to PZD-2 (P < 0.03). This study showed also that co-culture apparently compensates for any minor damage incurred during the PZD technique at the 2-cell and morula stages, (P < 0.01 and P < 0.01) respectively. Therefore PZD and co-culture seem mutually beneficial techniques that promote early blastocyst hatching in the mouse. PMID- 8501193 TI - A simplified method for R banding of human oocyte chromosomes. AB - A simple and reliable R banding technique was developed for karyotyping mature human oocytes. The banding quality obtained is sufficient for the diagnosis of specific aneuploidies and the discrimination between whole chromosomes and separated chromatids. The ability to karyotype human oocytes accurately will facilitate study of the aetiology of chromosomal abnormalities in human concepti. PMID- 8501194 TI - Fractured zona oocytes in in-vitro fertilization cycles stimulated with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin. AB - In order to assess the possible influence of gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin on the occurrence of fractured zona oocytes (FZOs) in in-vitro fertilization (IVF) treatment cycles, we analysed 267 consecutive cycles in 199 patients. In 87 cycles, at least one fractured zona oocyte was recovered, and in 180 cycles only intact zona oocytes (IZOs) were recovered. FZOs represented 5.8% of all oocytes retrieved and 14.8% when only cycles with FZOs were considered. Serum oestradiol concentrations were significantly higher at day -3 and day -2 (P < 0.02) in cycles yielding at least one fractured zona oocyte compared to IZO cycles (day 0 = retrieval day), and there was a higher incidence of G terminal pattern of oestradiol curve (P < 0.01) in cycles with FZOs. The mean numbers of all oocytes retrieved and of mature oocytes were significantly higher in FZO than in IZO cycles (P < 0.001). The fertilization rate of mature oocytes was significantly reduced (P < 0.05) in cycles with one or more oocytes with fractured zonae. There was no significant difference in the number of embryos transferred, pregnancy and abortion rates in both groups. We conclude that although the occurrence of fractured zona oocytes is a frequent event, it does not affect the overall results of our IVF programme. Zona pellucida fragility may be the result of over-maturation of some oocytes. PMID- 8501195 TI - Cytoskeletal organization and zona sensitivity to digestion by chymotrypsin of frozen-thawed mouse oocytes. AB - Mouse oocyte-cumulus masses were added to 1.5 dimethyl sulphoxide (DMSO) + 20% fetal bovine serum (FBS) that had been precooled at +4 degrees C, were frozen by slow cooling to an intermediate temperature of -60 degrees C before being plunged into liquid nitrogen at -196 degrees C, subjected to a controlled thaw, expelled into 1.5 M DMSO + FBS at 4 degrees C, and then washed in medium + FBS at 37 degrees C. Of 7733 oocytes treated, 78.4% were viable (controls; no treatment: 94.2% of 2764 oocytes; cryoprotectant only: 92.2% of 2991 oocytes). The oocyte losses were not due to complete loss of all oocytes from some straws or mice, since analysis of individual straws containing oocytes from a single mouse revealed considerable inter-straw/mouse variation. Amongst surviving oocytes, no significant differences between frozen and control oocytes in spindle, chromosomal or microfilament organization were recorded. Two significant differences were observed: (i) fewer frozen-thawed oocytes had zonae resistant to chymotrypsin digestion, and (ii) spindle organization in control oocytes, but not frozen-thawed oocytes, was improved by 3 h incubation at 37 degrees C. More of the abnormal than the normal frozen-thawed and control oocytes were surrounded by zonae which were resistant to digestion by chymotrypsin. PMID- 8501196 TI - Precise sex selected births of mice following single cell embryo biopsy and Y linked testis-specific gene analysis. AB - We report on the birth of 39 mice following single cell embryo biopsy and precise sex determination following in-vitro fertilization. Polymerase chain reaction was used to amplify fragments of the mouse testis-specific gene sequence (pYMT2/B) on the Y chromosome and the ovary-specific gene (ZP3) sequence on chromosome 5 from the single biopsied cell. Embryo biopsy was not associated with any deleterious effects. PMID- 8501197 TI - Ultrasonographic detection of a live fetus in recurrent spontaneous abortion during the first trimester. AB - To examine whether recurrent spontaneous abortion (RSA) can be distinguished from repeated sporadic spontaneous abortion, the clinical course of 38 cases with three or more consecutive and unexplained first trimester RSAs were retrospectively investigated in this study. For comparison with controls, the clinical course was examined of 38 fertile females, who had had sporadic abortions. In 19 (50%) RSAs and 6 (16%) controls, fetal cardiac activity was demonstrated by ultrasound during the course of pregnancy. The rate of detection of live fetus during pregnancy or at 8 weeks +/- 7 days gestation, was significantly greater in the RSA group compared to the control. The rate of vaginal bleeding before spontaneous abortion was significantly less in the RSA group than in the control group. There was no difference between the two groups in age or gestational age at spontaneous abortion. The patients with RSA were all examined for antiphospholipid antibodies in their sera and these were detected in eight of them. However, there was no difference in the rate of positive fetal cardiac activity between the RSA patients who tested positive or negative for antibody. These results reveal that the clinical course of RSA is very different from the course of sporadic abortion. Although sporadic abortion is a common complication of pregnancy, RSA is not a random repeated abortion, but rather a separate disease from sporadic abortion in normal fertile females. PMID- 8501198 TI - Local medical treatment of interstitial pregnancy after in-vitro fertilization and embryo transfer (IVF-ET): two case reports. AB - Two cases of interstitial pregnancy (one singleton, one heterotopic twins) were confirmed 31 and 34 days after in-vitro fertilization. Serum human chorionic gonadotrophin concentrations were 35,000 and 86,000 mlU/ml, respectively. They were treated conservatively with transvaginal ultrasonically guided intra-ovular injection of either methotrexate in the singleton pregnancy, or potassium chloride into the ectopic sac of the heterotopic twins. No complications were observed. The intra-uterine pregnancy continued and the patient delivered a 3350 g healthy baby at 39 weeks. PMID- 8501200 TI - Selective reduction of multifetal pregnancies in the first trimester using colour Doppler ultrasonography. AB - In pregnancies with multiple gestation, an adverse outcome is directly proportional to the number of fetuses within the uterus, primarily because of an increased predisposition to premature delivery. Although there is a good deal of information about multifetal reduction in triplets and quadruplets and even quintuplets, there is very little on sextuplets, and virtually nothing on septuplets. Among the different techniques proposed for selective termination, two approaches have been more widely adopted: transcervical aspiration and transabdominal needling of the embryo using grey scale ultrasonography, but as yet there is no report on multifetal reduction using colour Doppler ultrasound. A method for selective termination of multiple pregnancy using transabdominal colour Doppler ultrasonography has been described here for the first time in a case of septuplets. PMID- 8501199 TI - Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2. AB - Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas and in fetal adrenal cortex, whereas fetal medullary cells were fetal antigen 1 negative. In adult specimens fetal antigen 1 was exclusively found within the beta cells of the islets of Langerhans and in the adrenals with pronounced staining in the cortex. Our observations suggest that fetal antigen 1 is encoded by the mRNA defined by the cDNA clone pG2, but definitive sequencing and expression studies of this mRNA have not been achieved. PMID- 8501201 TI - Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy? AB - Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function. PMID- 8501202 TI - Delayed interval delivery in quadruplet pregnancy: a case report. AB - A case report of delayed delivery of a quadruplet pregnancy is presented. This quadruplet pregnancy resulted from in-vitro fertilization. To our knowledge, this case represents the first report of quadruplets delivered on three separate days using the technique of delayed interval delivery. All infants survived and are healthy 2 years later. PMID- 8501203 TI - Identification of Leuconostoc spp. by analysis of soluble whole-cell protein patterns. AB - Leuconostoc spp. share several physiologic characteristics, which sometimes makes it difficult to identify these organisms to the species level. We developed a system, based on the patterns of soluble whole-cell proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, that was able to discriminate between the six Leuconostoc spp. that are capable of growth at 37 degrees C. Nine unidentified Leuconostoc-like bacterial isolates that were included in the study did not fit any of the protein profiles of the type strains and may represent new Leuconostoc spp. PMID- 8501204 TI - Polymerase chain reaction for detection of measles virus in clinical samples. AB - A rapid and sensitive one-step reverse transcription polymerase chain reaction assay was developed to detect measles virus (MV) in nasal aspirates from patients with suspected MV infection. Oligonucleotide primers and probe were targeted to highly conserved regions of the matrix gene. Assay conditions were optimized to allow detection of as little as 1 PFU of an MV stock whose titer was known. Extraction of RNA from 38 nasal aspirates and then reverse transcription and MV matrix gene amplification yielded a polymerase chain reaction product of the predicted size in 14 of 14 MV culture-positive patients. Matrix gene amplification provides a rapid, sensitive, and specific supplementary assay to the currently available modalities for MV detection. PMID- 8501205 TI - Detection of polymerase chain reaction-amplified human immunodeficiency virus type 1 proviral DNA with a digoxigenin-labeled RNA probe and an enzyme-linked immunoassay. AB - An enzyme-linked immunoassay (EIA) combined with a solution hybridization (SH) reaction was devised to detect human immunodeficiency virus type 1 (HIV-1) provirus amplified by the polymerase chain reaction (PCR). In this nonisotopic PCR assay, designated PCR-EIASH, a fragment of the HIV-1 gag gene from peripheral blood mononuclear cells (PBMCs) was first amplified with biotinylated primers. The biotinylated amplified DNA segment was reacted in solution with an internal RNA probe labeled with digoxigenin-11-UTP. Hybrids were captured in a microtiter plate coated with streptavidin. Specific bound hybrids were quantitated by the addition of an enzyme-labeled antibody against digoxigenin and a fluorogenic substrate. The hybridization, immunological, and amplification parameters of PCR EIASH were optimized as follows: 12.5 pmol of each primer was used in the PCR; the reannealing reaction of amplified products with the RNA probe, which was used at 0.30 microgram/ml, was completed in 30 min at 70 degrees C in 2x SSC (1x SSC is 0.15 M NaCl plus 0.015 M sodium citrate). Five copies of HIV-1 DNA diluted in a lysate of 100,000 PBMCs from a seronegative control could be detected by PCR EIASH with a signal of 41 +/- 3 fluorescent units above a background noise of 13 +/- 2 fluorescent units. A total of 91 PBMC lysates from 91 seropositive patients sampled once and 20 PBMC lysates from 10 seropositive patients sampled twice were tested in duplicate in the PCR-EIASH; 107 samples were positive in duplicate tests, 1 sample was indeterminate, and 3 samples were negative. Of the latter three samples, one became positive by diluting the cell lysate, suggesting the presence of an inhibitor of Taq polymerase. The three samples negative for HIV-1 by PCR-EIASH were also negative when amplified with SK145-SK39 and detected with 32P-labeled SK102. PMID- 8501206 TI - Isolation of specific DNA fragments of Mycobacterium avium and their possible use in diagnosis. AB - We cloned and sequenced two DNA fragments (DT1 and DT6) from Mycobacterium avium serotype 2 for use in the identification of members of the M. avium-M. intracellulare complex (MAC). Reference strains of MAC belonging to serovars 1 to 28 were examined by using these DNA fragments as probes. The study revealed that the DT6 probe hybridized with DNAs from M. avium strains (serovars 1 to 6, 8 to 11, and 21), while the DT1 probe hybridized with DNAs from serovars 2, 3, 7, 12 to 20, and 23 to 25. DT1- and DT6-derived oligonucleotides were selected for use as primers in a polymerase chain reaction test. Amplification of the DT1 and DT6 sequences may provide the basis for a rapid and reliable assay for the detection of mycobacteria belonging to MAC. PMID- 8501207 TI - Monoclonal antibody-based blocking enzyme-linked immunosorbent assay for specific detection and titration of peste-des-petits-ruminants virus antibody in caprine and ovine sera. AB - A blocking enzyme-linked immunosorbent assay (B-ELISA), using two neutralizing monoclonal antibodies (MAbs), was established and compared with the virus neutralization test (VNT) for detecting specific peste-des-petits-ruminants virus (PPRV) antibody in caprine and ovine sera. This technique was developed because VNT, the only available specific serological test for PPRV and the cross-reactive rinderpest virus (RPV), is time-consuming and unaffordable for most laboratories in regions where both peste des petits ruminants and rinderpest occur. The test depends on the blocking of the binding of the MAb to a specific epitope in the presence of positive serum. Test conditions were optimized by using peste-des petits-ruminants and rinderpest sera that were known to be VNT positive and negative. A blocking format, in which serum is preincubated with a solid-phase PPRV antigen and then incubated with the MAb, yielded levels of sensitivity and specificity superior to those of a competitive format, in which the two reagents are added simultaneously. A threshold value of 45% inhibition, representing the mean for a negative population (n = 277) plus 2.7 standard deviations, was adopted for routine screening. A total of 605 serum samples were screened by B ELISA and the VNT. The sensitivity and specificity of B-ELISA relative to the VNT were 90.4 and 98.9%, respectively. Of 264 field serum samples tested, 11 (4.2%) could not be assayed by the VNT because of contamination or cytotoxicity; the overall agreement quotient between results of the two tests (n = 253) was 0.91. A high correlation (r>/=0.98) was observed between B-ELISA and the VNT for endpoint titration of sera (n=57). Because B-ELISA proved to be nearlyas sensitive and specific as the VNT while being simpler and more rapid, it would be an adequate substitute for the VNT for assessing herd immune status and for epidemiologic surveillance. PMID- 8501208 TI - Detection of Mycoplasma pneumoniae by polymerase chain reaction and nonradioactive hybridization in microtiter plates. AB - In order to improve the diagnosis of a Mycoplasma pneumoniae infection, we developed a polymerase chain reaction (PCR)-based assay. The gene encoding elongation factor Tu (tuf) was selected as the target sequence. Oligonucleotides derived from variable stretches of the tuf gene were able to prime the amplification of a 950-bp fragment exclusively when M. pneumoniae DNA was used as the template. The sensitivity of the assay was increased 10-fold when the amplification products were hybridized with an internal M. pneumoniae-specific oligonucleotide. The use of three to four genome copies for PCR was sufficient for obtaining a hybridization signal. In addition, we substituted radioactive filter hybridization with a microtiter plate assay. Via a biotin moiety of one PCR primer, the amplification products were immobilized on streptavidin-coated microtiter plates. Subsequent hybridization with a digoxigenin-labeled oligonucleotide resulted in the same sensitivity and specificity as those obtained by filter hybridization. Clinical application of the assay was performed on 102 throat swab specimens from patients with respiratory tract infections. Of 21 culture-positive samples, 19 were confirmed to be positive in the PCR-based assay (sensitivity, 90%). Furthermore, 14 of 19 seropositive but culture-negative samples gave a positive hybridization signal. Of 62 culture-negative and seronegative specimens, 60 gave a negative result in our assay (specificity, 97%). Of the 33 samples that were positive in our PCR-based assay, 5 samples initially gave false-negative results because of the presence of inhibitory substances in those specimens. Inhibition of Taq polymerase in these five cases was prevented by an additional step of phenol extraction and subsequent ethanol precipitation. PMID- 8501209 TI - Genotyping by multiplex polymerase chain reaction for detection of endemic hepatitis B virus transmission. AB - A nested polymerase chain reaction (PCR) protocol was developed for rapid genotyping of hepatitis B virus (HBV). During the first PCR round, a universal HBV primer pair was used to amplify the entire pre-S region of the HBV genome. Within the pre-S region, many nucleotide exchanges are observed. These are partly correlated to the serological hepatitis B surface antigen subtypes. Five additional subtype-specific primers were selected from that region which, together with two universal non-group-specific primers, generated specific combinations of two to four DNA fragments of defined sizes. By this approach, 55 hepatitis B surface antigen-positive patients from a pediatric oncology unit in Germany were analyzed. Fifty-four patients who had been infected within 2 years had an identical pattern in the multiplex PCR, suggesting a common source of infection and person-to-person transmission within the unit. One child who was infected 5 years later had a different PCR pattern and, therefore, must have been infected from a different source. Furthermore, 109 serum samples taken from pregnant Cameroonian women and 25 serum samples from their babies taken 6 months after birth were analyzed. In one case, mother-to-infant transmission of the virus was demonstrated. Apart from its role in epidemiological studies on HBV, multiplex PCR may also be a useful tool for rapid genetic analysis in other fields if there is a moderate degree of sequence variation which enables the design of specific primers. PMID- 8501210 TI - Chlamydia trachomatis infection in a high-risk population: comparison of polymerase chain reaction and cell culture for diagnosis and follow-up. AB - A study to compare the polymerase chain reaction (PCR) test with the cell culture method in diagnosing urogenital Chlamydia trachomatis infections was performed. From 497 patients (212 women, 285 men) attending an outpatient clinic for sexually transmitted diseases, a total of 814 samples (female patients, cervix and urethra; male patients, urethra) were collected. This total included follow up samples from 35 women and 35 men positive for C. trachomatis by cell culture and/or PCR test, which were collected 2 weeks after treatment with doxycycline (two 100-mg doses per day for 7 days). The PCR test was performed directly on clinical samples without performing phenol-chloroform extraction and ethanol precipitation of DNA. The prevalence of C. trachomatis as measured by positive cell culture was 64 of 497 (12.9%) for all patients, 31 of 212 (14.6%) for women, and 33 of 285 (11.6%) for men. The prevalences as measured by positive PCR test were 71 of 497 (14.3%), 36 of 212 (17.0%), and 35 of 285 (12.3%), respectively. The sensitivities of the cell culture and the PCR test compared with that of true positive samples were 77.5 to 78.4% and 99.0 to 100.0%, respectively. Discrepancies between cell culture and the PCR test were found for 23 of 497 patients (4.9%), 19 of 212 females (9.0%), and 4 of 285 males (1.4%). Nineteen pretreatment samples from 19 patients (4 female endocervical, 13 female urethral, and 2 male urethral samples) were cell culture negative and PCR test positive, while 1 pretreatment female endocervical sample was cell culture positive and PCR test negative. The posttreatment samples from all patients were cell culture negative, but the PCR test remained positive for 3 of 70 patients (1 female endocervical and 2 male urethral samples). One of these samples became spontaneously negative in three more weeks. The medical history of the individual patient and the negative PCR tests after treatment for nearly all patients support our hypothesis that the positive PCR test results were clinically relevant for the cell culture-negative but PCR test-positive but PCR test positive patients of the population studied. PMID- 8501211 TI - Application of polymerase chain reaction to fingerprinting Aspergillus fumigatus by random amplification of polymorphic DNA. AB - A new method for fingerprinting Aspergillus fumigatus by random amplification of polymorphic DNA (RAPD) by using single primers with arbitrary sequences is described. Five primers were examined with 19 isolates from six patients with aspergilloma as well as with A. fumigatus NCPF 2109. Two of the primers (GCT GGT GG and GCG CAC GG, 5' to 3') gave adequate discrimination between isolates, generating five and six types, respectively. Combination of the results obtained with each of these two primers generated 12 types. This compares very favorably with immunoblot fingerprinting and XbaI-generated restriction fragment length polymorphisms on the same isolates. Typeability and reproducibility were good with RAPD, and RAPD was less labor-intensive than immunoblot fingerprinting. RAPD typing results suggested that aspergillomas sometimes contain isolates of more than one type. PMID- 8501212 TI - Occurrence of bacterial endosymbionts in Acanthamoeba spp. isolated from corneal and environmental specimens and contact lenses. AB - Free-living and parasitic protozoa are known to harbor a variety of endosymbiotic bacteria, although the roles such endosymbionts play in host survival, infectivity, and invasiveness are unclear. We have identified the presence of intracellular bacteria in 14 of 57 (24%) axenically grown Acanthamoeba isolates examined. These organisms are gram negative and non-acid fast, and they cannot be cultured by routine methodologies, although electron microscopy reveals evidence for multiplication within the amoebic cytoplasm. Examination for Legionella spp. with culture and nucleic acid probes has proven unsuccessful. We conclude that these bacteria are endosymbionts which have an obligate need to multiply within their amoebic hosts. Rod-shaped bacteria were identified in 5 of 23 clinical Acanthamoeba isolates (3 of 19 corneal isolates and 2 of 4 contact lens isolates), 4 of 25 environmental Acanthamoeba isolates, and 2 of 9 American Type Culture Collection Acanthamoeba isolates (ATCC 30868 and ATCC 30871) previously unrecognized as having endosymbionts. Coccus-shaped bacteria were present in one clinical (corneal) isolate and two environmental isolates. There was no statistical difference (P > 0.8) between the numbers of endosymbiont strains originating from clinical (26% positive) and environmental (24% positive) amoebic isolates, suggesting that the presence alone of these bacteria does not enhance amoebic infectivity. Rods and cocci were found in both clinical and environmental isolates from different geographical areas (Seattle, Wash., and Portland, Oreg.), demonstrating their widespread occurrence in nature. Our findings suggest that endosymbiosis occurs commonly among members of the family Acanthamoebidae and that the endosymbionts comprise a diverse taxonomic assemblage. The role such endosymbionts may play in pathogenesis remains unknown, although a variety of exogenous bacteria have been implicated in the development of amoebic keratitis, warranting further evaluation. PMID- 8501213 TI - Isolation of gram-positive rods that resemble but are clearly distinct from Actinomyces pyogenes from mixed wound infections. AB - Beginning in 1990, gram-positive rods resembling Actinomyces pyogenes were found with increasing frequency in mixed cultures from various infectious processes, most of them from patients with otitis, empyema, pilonidal cysts, perianal abscesses, and decubitus ulcers. Ribotyping and hybridization showed that these gram-positive rods could be divided into five groups not related to known Actinomyces species. Biochemical markers for reliable differentiation into these groups, however, could not be found. Therefore, naming new species is not warranted unless parameters are discovered that allow identification without DNA hybridization. These gram-positive rods have been isolated only in mixed cultures with anaerobes, Staphylococcus aureus, Streptococcus "milleri," enterococci, and gram-negative rods. Their exact role in these possibly synergistic infections needs further investigation. PMID- 8501214 TI - Intracellular bacteria of porcine proliferative enteropathy: cultivation and maintenance in vitro. AB - An obligate intracellular bacterium was isolated from the intestines of all 10 cases of porcine proliferative enteropathy from four different pig farms. The organism grew in a rat enterocyte cell line (IEC-18) and was maintained over 20 passages. The growth of the bacteria was assessed by immunostaining of cells exposed to infection. Infection was not associated with morphological cell change, and growth was confined to cells infected at the time of each transfer of infection and the progeny of these cells. The bacterium is a microaerophilic, cell dependent, curved or rod-shaped, gram-negative bacillus that multiplies freely in the enterocyte cytoplasm. Cell cultures containing the intracellular bacteria appear to be free of other microorganisms, including chlamydiae and viruses. PMID- 8501215 TI - Serotype identification of Actinobacillus pleuropneumoniae by arbitrarily primed polymerase chain reaction. AB - Rapid and accurate determination of the Actinobacillus pleuropneumoniae serotype involved in a disease outbreak is important both in limiting the severity of an outbreak and for tracing the source of the infecting organism. This study describes the use of arbitrarily primed polymerase chain reaction (AP-PCR) as a rapid, precise, and genetically based procedure to identify A. pleuropneumoniae. AP-PCR amplification of bacterial genomic DNA results in specific DNA profiles, which can be used to differentiate currently recognized serotypes. This technique is especially useful for identifying previously nontypeable and serologically cross-reactive A. pleuropneumoniae field isolates. Consecutive passages of isolates on different media, freezing, and subsequent infection of pigs did not alter the AP-PCR genomic profile. We propose the use of M13 and T3-T7 oligodeoxynucleotide primers for diagnostic and epidemiological identification of A. pleuropneumoniae by AP-PCR techniques. PMID- 8501216 TI - Mitomycin immunoblot colony assay for detection of Shiga-like toxin-producing Escherichia coli in fecal samples: comparison with DNA probes. AB - We developed a direct screening immunoblot assay for the detection of Shiga-like toxin (SLT)-producing organisms in stool samples. The assay takes advantage of the phage-mediated nature of SLT production in Escherichia coli and the phage inducing effects of mitomycin. The addition of mitomycin significantly enhanced the amount of toxin available for immunologic detection. By using the mitomycin enhanced immunoblot assay, SLT-producing E. coli could be distinguished from non toxin-producing E. coli and normal stool flora in ratios of 1:1,000 to 1:5,000. The immunoblot assay was examined in a field setting and compared with direct DNA probing for SLT-I and SLT-II. The assay was able to detect SLT-producing E. coli with a high level of sensitivity and specificity. Specificity was markedly improved by using a monoclonal antibody which cross-reacts with both SLT-I and SLT-II B subunits in place of the polyclonal antitoxin sera. We conclude that the mitomycin-enhanced immunoblot colony assay is a rapid and reliable alternative to DNA probing for the detection of phage-mediated SLT-producing organisms in stool samples, especially when the production and use of nucleic acid probes are not feasible. In addition, it permits isolation of positive colonies for further study and confirmation. PMID- 8501217 TI - Collaborative evaluation of the Radiometer Sensititre AP80 for identification of gram-negative bacilli. AB - A multicenter trial of the Sensititre AP80 panel read on the Sensititre AutoReader (Radiometer America, Westlake, Ohio) for the automated identification of gram-negative bacilli was conducted with 1,023 clinical isolates (879 members of the family Enterobacteriaceae plus 144 nonenteric organisms). Assignment of taxa was based on the computer-assisted interpretation of the results of a series of reactions with fluorogenic enzyme substrates after 5 h of incubation, with an incubation interval of approximately 18 h used when indicated. Accuracy was determined initially by comparison with the results obtained with the API 20E or Rapid NFT system (Analytab Products, Plainview, N.Y.). Isolates showing discrepancies were identified by using conventional biochemical profiles. Identifications were available after 5 h of incubation for 918 isolates (90%). Agreements with reference results for members of the family Enterobacteriaceae were 95.3 and 92.5% at the genus and species levels, respectively, and for the nonmembers of the family Enterobacteriaceae, the agreements with reference results were 95.1 and 84.7%, respectively. The Sensititre AP80 panel was found to be simple and convenient to use, allowed for the testing of three isolates per panel, required minimal supplementary testing for completion of identification, performed in a reproducible fashion, and demonstrated an accuracy of same-day identification comparable to that reported for other automated systems. The AP80 panel appears well suited for routine use in the clinical microbiology laboratory as an automated means of identifying both members of the family Enterobacteriaceae and nonenteric gram-negative bacilli. PMID- 8501218 TI - Clonal structure and pathogenicity of Shiga-like toxin-producing, sorbitol fermenting Escherichia coli O157:H-. AB - We compared a collection of sorbitol-fermenting (SF) Escherichia coli O157:H- strains with SF E. coli O157:H45 and non-SF E. coli O157:H7 and E. coli O157:H- strains by pulsed-field gel electrophoresis. The SF E. coli O157:H- strains had identical or closely related XbaI patterns that differed markedly from those for the other E. coli O157 strains. Plasmid content and the presence of Shiga-like toxin-converting phages were determined for the SF E. coli O157:H- strains, indicating that these strains harbor a single 90-kb plasmid. They are lysogenized by toxin-converting phages and harbor the eae gene. Nonmotile E. coli O157 strains were observed to adhere more efficiently to HEp-2 cells than the motile strains. From their phenotypic and genotypic features, the SF E. coli O157:H- strains may well represent a new clone with non-SF E. coli O157:H7 pathogenic characteristics. PMID- 8501219 TI - Expression of hemolytic activity by Plesiomonas shigelloides. AB - More than 90% of the Plesiomonas shigelloides strains that we tested produced a beta-hemolysin, as judged by the results of agar overlay and contact-dependent hemolysis assays. The hemolysin was cell associated, was active against the erythrocytes of various animal species, and was synthesized at both 25 and 35 degrees C. Activity was lost after thermal or proteolytic treatments or after preincubation in the presence of gentamicin; hemolytic activity did not appear to correlate with the previously established 50% lethal doses for seven of these strains. The hemolysin may play a role in iron acquisition in vivo via the lysis of erythrocytes, liberating hemoglobin, or, alternatively, may be involved in gastrointestinal disease. PMID- 8501220 TI - Direct detection of Chlamydia trachomatis in urine specimens from symptomatic and asymptomatic men by using a rapid polymerase chain reaction assay. AB - Screening for Chlamydia trachomatis infection in men has traditionally been limited to men who present with urethral symptoms, thereby limiting the detection of asymptomatic chlamydia infection in men. In order to effectively screen both symptomatic and asymptomatic men, we evaluated a newly developed polymerase chain reaction (PCR) assay, Amplicor C. trachomatis, from Roche Molecular Systems for the detection of C. trachomatis in urine specimens in comparison with urethral culture. A total of 530 male urine specimens were collected from 322 symptomatic and 208 asymptomatic men attending two sexually transmitted disease clinics in Baltimore, Md. The prevalence of C. trachomatis by culture was 9.8% (10.6% in symptomatic men and 8.2% in asymptomatic men). Compared with culture, the sensitivity of the PCR was 92.8%, the specificity was 94.7%, the positive predictive value was 68.4%, and the negative predictive value was 99.1%. Discrepant results between culture and PCR were further analyzed by direct fluorescent-antibody staining of elementary bodies in urine sediment and in culture transport vials and by major outer membrane protein PCR of transport media for specimens with negative culture. The revised sensitivity and specificity of PCR for urine were 95.0 and 99.8%, respectively, and the positive and negative predictive values were 98.7 and 99.1%, respectively. The sensitivity of culture compared with PCR and/or direct fluorescent-antibody staining was 68.4%. These results indicate that the PCR assay is a highly sensitive and specific assay for the detection of C. trachomatis in male urine specimens and provides a noninvasive technique for routine screening of chlamydia infection in both symptomatic and asymptomatic men. PMID- 8501221 TI - Comparative study of procedures for isolation and cultivation of Legionella pneumophila from tap water in hospitals. AB - For the isolation and cultivation of Legionella pneumophila from tap water in hospitals, we compared different media and selection techniques. A second part of the study compared the L. pneumophila yields from different water samples at identical sites. A total of 210 water samples (500 ml each) were collected from two selected sites in each of 21 hospitals. Warm water samples were collected after flow times of 0, 5, 10, and 15 min; in addition, one cold water sample was collected. Filtration was used to concentrate all samples. Following filtration, 0.1 and 1 ml each of untreated samples, heat-treated samples (3 min, 59 degrees C), and acid-treated samples (pH 2.2, 15 min) were spread onto the selective media MWY (SR 118; Oxoid) and BMPA alpha (SR 111; Oxoid), and samples from 12 hospitals were also spread onto GVPC medium (SR 152; Oxoid). A total of 72 (34%) of the 210 samples from 12 hospitals were positive. With respect to the positive Legionella cultures, there was no significant difference between the selective media MWY, BMPA alpha, and GVPC. With the BMPA alpha supplement, more samples were positive following heat treatment (P < 0.05) or acid treatment (P < 0.05) than without any further treatment. For the maximum yield of Legionella colonies with minimum additional microbial flora, acid treatment was the most effective, and by all methods, the GVPC supplement was the most selective. For routine water tests in hospitals for differentiating between systemic and local contamination, acid treatment of the concentrated samples, the use of different selective media, and the correct selection of sampling sites are recommended. PMID- 8501222 TI - Evidence for two genetic variants of Pneumocystis carinii coinfecting laboratory rats. AB - Pneumocystis carinii pneumonia is an oftentimes fatal infection for hosts in an immunocompromised state. The disease occurs in a wide variety of mammals, but the etiologic agent of this disease has been referred to as P. carinii regardless of the host species. However, even within a single host species, such as laboratory rats, distinct varieties of P. carinii have been identified from differences in the electrophoretic migration of chromosomes in agarose gels. Here we present evidence indicating that some laboratory rats can contain two different genetic variants of P. carinii that differ not only in electrophoretic karyotype but also in the presence of a particular repeated DNA sequence, in the presence of an intron in the 18S ribosomal RNA gene, and in the sequence of part of the 18S rRNA gene. Most of the rat colonies studied were infected with P. carinii that contained the repeated DNA and the 18S rRNA gene intron. The other type of rat derived P. carinii, which lacked the repeated DNA and the intron in the 18S rRNA gene, was found as a coinfection with the first. Parasite populations from different coinfected rats contained the two variants in different proportions. PMID- 8501223 TI - Identifying bovine respiratory syncytial virus by reverse transcription polymerase chain reaction and oligonucleotide hybridizations. AB - An assay to identify tissue culture cells infected with bovine respiratory syncytial virus (BRSV) that utilizes reverse transcription (RT), the polymerase chain reaction (PCR), and a synthetic oligonucleotide hybridization probe has been developed. The RT-PCR assay uses a BRSV-specific negative-sense oligonucleotide primer to synthesize cDNA from a BRSV fusion protein mRNA template and another BRSV-specific oligonucleotide primer (positive sense) upstream from the negative-sense primer for PCR amplification. In the presence of mRNA templates of BRSV isolates originating from locations throughout the United States, the BRSV RT-PCR assay resulted in amplified products (381 bp) that were specific to BRSV, as demonstrated in hybridizations with a positive-sense oligonucleotide probe complementary to internal sequences and in sequence comparisons with the F protein of BRSV 391-2. In analysis of the BRSV RT-PCR assay with prototype strains of human RSV subgroups A and B, amplification of a similar 381-bp RT-PCR product was not evident, and no RT-PCR product hybridized with the internal probe. We conclude that the specific ability to amplify DNA sequences of BRSV F protein mRNA by RT-PCR and then to demonstrate the presence of the amplified product with a BRSV-specific oligonucleotide probe will greatly add to the speed, sensitivity, and specificity of BRSV diagnostics. PMID- 8501224 TI - Identification of spheroplast-like agents isolated from tissues of patients with Crohn's disease and control tissues by polymerase chain reaction. AB - Mycobacterium paratuberculosis has been isolated from tissue taken from patients with Crohn's disease and has been implicated in the etiology of this disease. On culture, the organisms appear initially as cell wall-deficient, spheroplast-like forms that are difficult to identify by conventional techniques. Here we examine 30 unidentified cultures by the polymerase chain reaction using primers specific for M. paratuberculosis, Mycobacterium tuberculosis, and Mycobacterium avium restriction fragment length polymorphism type A/I and also by a non-species specific mycobacterial polymerase chain reaction. Six of these cultures, all from Crohn's disease, were shown to contain DNA from M. paratuberculosis. Cultures from both Crohn's disease and controls were found to contain mycobacterial DNA of unknown specific origin. PMID- 8501225 TI - Testing of Streptococcus pneumoniae for resistance to penicillin. AB - The increasing prevalence of penicillin-resistant Streptococcus pneumoniae requires antibiotic susceptibility tests that can be done with greater ease and reliability. We measured the MIC of penicillin for pneumococci by the tube macrodilution method with Mueller-Hinton broth (MHB), Haemophilus Test Medium (HTM), Todd-Hewitt broth with 0.5% yeast extract (THY), and MHB with 3% lysed horse blood (LHB). Eight (19%) and 6 (14%) of 42 pneumococcal isolates failed to generate turbid growth in MHB and HTM, respectively, whereas all pneumococcal isolates did so in THY and LHB. For those strains that replicated to turbidity, the mean MICs of penicillin were lower in MHB and HTM than in THY and LHB, with differences being significant (P < 0.05) for comparisons with LHB. Four isolates appeared to be penicillin susceptible in HTM but were actually moderately resistant in THY and LHB, and two isolates appeared to be moderately resistant but were resistant. A similar failure to detect resistance was seen with MHB. S. pneumoniae ATCC 49619, a moderately penicillin-resistant strain that has been proposed for quality control testing, gave variable results in MHB or THM and appeared to be susceptible to penicillin in some assays, whereas the MICs for S. pneumoniae ATCC 49619 in THY or LHB fell within a twofold dilution range, with geometric means of 0.16 and 0.18 micrograms/ml, respectively. Pneumococcal isolates thus may appear falsely susceptible to penicillin when tested in MHB or HTM. LHB remains the standard medium; however, because THY is an easily prepared clear medium that can be used in automated systems and appears to yield results similar to those obtained with LHB, THY deserves consideration for routine use. PMID- 8501226 TI - Standardization of medium for culturing Lyme disease spirochetes. AB - To standardize the procedure for isolating and culturing Lyme disease spirochetes, we modified the composition of the medium generally used for this purpose (BSK-II) and developed a system for its distribution. This medium contains no gelatin or agarose, and various components are used in proportions that differ from those in BSK-II. Each of the major proteinacious components was screened by substitution in samples of the complete product. The final medium was evaluated for the capacity to grow related spirochetes including Borrelia burgdorferi N40, Guilford, and JD-1 as well as strains of Borrelia hermsii (HS-1) and of Borrelia coriaceae (CO53). Each isolate developed from inocula containing as few as one to five organisms. Doubling time of B. burgdorferi during log-phase growth at 37 degrees C was 10 to 12 h. Lyme disease spirochetes were isolated in this medium from ear punch biopsies and dermal aspirates from naturally infected mice and rabbits, from dermal biopsies from a human patient, and by sampling field-collected deer ticks (Ixodes dammini). Cultured spirochetes remained infective to mice and to ticks. The medium can be stored at -20 degrees C or lower temperatures for at least 8 months without effect on its ability to support growth of small inocula to densities exceeding 10(8) spirochetes per ml. Lyme disease spirochetes remained infective to mice after being stored at -80 degrees C in this medium for at least 8 months. We anticipate that the availability of this standardized medium (Sigma Chemical Co.), supplemented with prescreened rabbit serum, will facilitate comparison of research results between laboratories and may eventually permit definitive clinical diagnosis of Lyme disease based on demonstration of the pathogen. The standardized medium is designated BSK-H. PMID- 8501227 TI - Determination of the optimal cutoff value for a serological assay: an example using the Johne's Absorbed EIA. AB - Traditionally, in order to improve diagnostic accuracy, existing tests have been replaced with newly developed diagnostic tests with superior sensitivity and specificity. However, it is possible to improve existing tests by altering the cutoff value chosen to distinguish infected individuals from uninfected individuals. This paper uses data obtained from an investigation of the operating characteristics of the Johne's Absorbed EIA to demonstrate a method of determining a preferred cutoff value from several potentially useful cutoff settings. A method of determining the financial gain from using the preferred rather than the current cutoff value and a decision analysis method to assist in determining the optimal cutoff value when critical population parameters are not known with certainty are demonstrated. The results of this study indicate that the currently recommended cutoff value for the Johne's Absorbed EIA is only close to optimal when the disease prevalence is very low and false-positive test results are deemed to be very costly. In other situations, there were considerable financial advantages to using cutoff values calculated to maximize the benefit of testing. It is probable that the current cutoff values for other diagnostic tests may not be the most appropriate for every testing situation. This paper offers methods for identifying the cutoff value that maximizes the benefit of medical and veterinary diagnostic tests. PMID- 8501228 TI - Detection and characterization of the eae gene of Shiga-like toxin-producing Escherichia coli using polymerase chain reaction. AB - In this study, the polymerase chain reaction (PCR) was used in the detection of the attaching and effacing (eae) gene of Shiga-like toxin-producing Escherichia coli (SLT-EC). Oligonucleotide primers, complementary to the 5' portion of the eae gene of the enteropathogenic E. coli E2348/69 (O127:H6) and of SLT-EC CL8 and EDL933 (O157:H7), generated PCR products of the predicted sizes with DNA from the majority of human clinical SLT-EC strains tested from O serogroups 5, 26, 103, 111, 121, 128, 145, and 157; all SLT-EC strains of O serogroups 5, 26, and 111 from cattle; and a minority of porcine SLT-EC strains (one strain each from O serogroups 107 and 130 and one rough strain). Five HaeIII digestion profiles were obtained for PCR products generated by amplification of a 2.3-kb DNA fragment from the 5' end of eae. The HaeIII profiles for SLT-EC O serogroups, such as 26, 103, and 157, differed from each other but were consistent among strains within these O serogroups. Oligonucleotide primer pairs complementary to the 3' end of either the O127:H6 E. coli or the O157:H7 eae nucleotide sequence only amplified DNA from E. coli strains from a few of the SLT-EC O serogroups examined. One primer pair with homology to the 3' nucleotide sequence of eae from E. coli O157:H7 appeared to be relatively specific for this O serogroup by PCR. No PCR products were obtained in amplification experiments with the eae primers using DNA from human SLT-EC of O serogroups 38 (1 0f 1) and 91 (3 or 3), 15 of 15 SLT EC strains from edema disease, or 29 of 29 non-SLT-EC strains from pigs and calves with diarrhea. PMID- 8501229 TI - Accuracy of reporting of methicillin-resistant Staphylococcus aureus in a provincial quality control program: a 9-year study. AB - We report the results of a province-wide quality control program in which five methicillin-resistant Staphylococcus aureus strains were circulated to all Ontario laboratories (hospital, private, and public health laboratories) on nine occasions between 1980 and 1989. The level of expression of methicillin resistance in each of the isolates was determined by performing viable colony counts on serial dilutions of methicillin in agar, and each isolate was assigned to an expression class according to previous published criteria (A. Tomasz, S. Nachman, and H. Leaf, Antimicrob. Agents Chemother. 35:124-129, 1991). Over this time there was an improvement in the performance of laboratories in the recognition of three strains that were relatively easy to detect (strains B, C, and E). These strains were of expression class II, and 98% of laboratories reported correct identifications in 1986. Performance in identifying two strains (strains A and D) of expression class I remained poor. Strain A was circulated in two surveys in 1987 and 1989, and laboratories were sent a questionnaire requesting details of the methods used in those two surveys. The methods used by the laboratories were classified into three categories: disk diffusion, single plate screening by agar incorporation, and automated methods, which included premanufactured MIC panels. Between the 1987 and 1989 surveys, there was no change in the performance of the disk diffusion test (60% correct on both occasions), but there was improvement in the sensitivity of the agar incorporation test (36% correct in 1987 and 84% correct in 1989) and in automated methods (43% correct in 1987 and 79% correct in 1989). Over a decade, there was overall improvement in the performance of laboratories in detecting easy-to detect strains, but there were difficulties in detecting organisms of low expression class, and an organism of very low expression class should be designated as a control organism for routine testing of methicillin-resistant s. aureus isolates. PMID- 8501230 TI - Epidemiologic analysis and genotypic characterization of a nosocomial outbreak of vancomycin-resistant enterococci. AB - We are reporting on a nosocomial outbreak of 213 cases of vancomycin-resistant enterococcus infection involving 2,812 enterococcal isolates from patients over a period of 36 months. In 1990, the Enterococcus faecium vancomycin susceptibility rate was found to be 85.7% (36 of 42 cases), and an incidence of 10.9% (42 of 383) was noted. The 1991 data showed E. faecium with a vancomycin susceptibility rate of 61.8% (110 of 178) and an incidence of 26.0% (178 of 684). Subsequently, in 1992, the incidence of E. faecium increased to 34.0% (599 of 1,745), with a decreased vancomycin susceptibility rate of 25.8% (155 of 599). The E. faecalis vancomycin susceptibility rate remained near 97% (1,768 of 1,823) over the 36 month period. Of 115 vancomycin-resistant enterococcus (VRE) clinical isolates identified by the MicroScan MIC Combo-6 panels (Baxter Healthcare, Sacramento, Calif.), the agar dilution method indicated the resistance rate to be 92.3% (106 of 115) (high level), 3.5% (4 of 115) midlevel, and 3.5% (4 of 115) (low level). Genotypic characterization of 32 different VRE isolates by field-inversion gel electrophoresis demonstrated 19 dissimilar restriction endonuclease patterns, with 9 patterns associated with VRE quinolone resistance. Statistical analysis of case-control data for 32 patients with VRE infections indicated a positive association with intrabdominal surgical procedures (odds ratio, 24.12), multidrug therapy (odds ratio, 37.80), preexposure to vancomycin (odds ratio, 20.21), and death (odds ratio, 17.50). PMID- 8501231 TI - Innovative index system for reporting microbiology laboratory results. AB - A new computerized format for presenting microbiology laboratory results has been designed and evaluated. This new system uses an index format providing a concise summary of the status of each test ordered and the results for each test organized by the source of the specimen on the first page of the report. This is followed by complete, detailed microbiology results sorted in reverse chronological order. This new system was significantly (P < 0.05) faster and easier to use than a standard source-category reporting system used in many hospitals. In addition, the index format was overwhelmingly preferred by the individuals evaluating both systems. PMID- 8501232 TI - Fluorometric quantitation of broth-cultured mycoplasmas by using alkaline ethidium bromide. AB - We developed a fluorometric system which does for broth-grown mycoplasmas what turbidimetric analysis does for broth-grown bacteria. It allows one to monitor the growth of broth-grown mycoplasmas at any interval desired. The entire procedure is quick, taking not more than 20 min. The fluorometric readings correlate with colonial growth on agar, making it possible, for the first time, to take readings which closely estimate the CFU present in the culture at a given moment in time. We show that this system can be used to assess the effectiveness of an antimycoplasmal antibiotic and to optimize medium components and that fluorometer readings taken during the logarithmic phase of growth correlate with the DNA content of the viable cells. Use of this methodology will permit investigators to know absolutely the phase of the growth cycle of the culture concomitant with the growth of the culture itself, and since fluorometer readings of culture aliquots can be converted to DNA equivalents, the standardization of mycoplasmal cultures within and between laboratories will be a possibility. PMID- 8501233 TI - Development of an enzyme-labeled oligonucleotide probe for the cholera toxin gene. AB - An alkaline phosphatase-conjugated 30-mer oligonucleotide probe was developed to detect the cholera toxin gene (ctx) in Vibrio cholerae O1. For rapid identification, V. cholerae O1 was grown on selective agar (thiosulfate-citrate bile salts agar) or in alkaline peptone water and organisms were transferred directly to nylon membranes. Lysis of cells, denaturation of DNA, neutralization, and hybridization were carried out on the membrane. These procedures required only 3 h for completion. The results of the hybridization test with 88 clinical and 20 environmental isolates agreed almost exactly with the results of the immunological tests (anti-cholera toxin antibody-sensitized latex agglutination tests). The specificity of the probe was also tested with strains of enterotoxigenic Escherichia coli, V. cholerae non-O1, and Vibrio mimicus. PMID- 8501235 TI - Species distribution of coagulase-negative staphylococcal isolates at a community hospital and implications for selection of staphylococcal identification procedures. AB - A total of 499 coagulase-negative staphylococci (CoNS) were isolated from a variety of clinical specimens at a community hospital. Ten different species and many strains of CoNS were identified. Staphylococcus epidermidis was the most common isolate. The species distribution suggests that S. saprophyticus and, to a lesser extent, S. haemolyticus may be important in urinary tract infections. S. lugdunensis may be a significant isolate from wound infections. Frequently, mixed cultures were found with either multiple species or multiple strains of the same species of CoNS. These mixed cultures could not be detected by colony morphology upon initial overnight incubation of the cultures but could be distinguished following colony development for several days. In addition, sequential positive cultures from an individual patient often yielded different species or different strains of the same species which again could not be detected upon initial observations of colony morphology. Procedures for the identification of the CoNS need to be improved, and microbiology laboratories should consider the use of more definitive identification procedures for the CoNS. PMID- 8501234 TI - Epidemic of diarrhea caused by Vibrio cholerae non-O1 that produced heat-stable toxin among Khmers in a camp in Thailand. AB - An epidemic of a cholera-like disease occurred among Khmers in a camp in Aranyaprathet, Thailand, in May 1990. Of 215 patients with diarrhea, Vibrio cholerae O1 was isolated from 25 (12%) and V. cholerae non-O1 was isolated from 15 (7%). Five of 15 (33%) non-O1 V. cholerae isolates hybridized with two different oligonucleotide probes previously used to detect V. cholerae non-O1 that produces a heat-stable toxin. This is the first description of an epidemic of diarrhea caused by V. cholerae non-O1 that produces heat-stable toxin. PMID- 8501236 TI - Evaluation of the Vitek Systems Gram-Positive Identification card for species identification of coagulase-negative staphylococci. AB - Vitek Systems' Gram-Positive Identification test (GPI) card was evaluated for the ability to identify 12 coagulase-negative Staphylococcus species and subspecies. The bionumber generated from the GPI card was examined for its potential use in epidemiological studies. Results indicated that the GPI card had a high degree of correlation with the conventional methods of identification. The species identified with the greatest accuracy were Staphylococcus epidermidis (92%), S. haemolyticus (95%), S. capitis subsp. capitis (88%), and S. saprophyticus (100%). S. hominis (63%) was identified with the least accuracy. The bionumber was found to have limited epidemiological value because of the frequent occurrence of a few major bionumbers. PMID- 8501237 TI - Identification of a novel group of Serpulina hyodysenteriae isolates by using a lipopolysaccharide-specific monoclonal antibody. AB - A monoclonal antibody to Serpulina hyodysenteriae 8930 was produced and was used to probe pronase-treated cell lysates of S. hyodysenteriae isolates in immunblots. The results showed that the monoclonal antibody was specific for only five closely related S. hyodysenteriae isolates: 8930, 5380, 70A, RMIT 88, and RMIT 97. PMID- 8501238 TI - Comparative assessment of the leprosy antibody absorption test, Mycobacterium leprae extract enzyme-linked immunosorbent assay, and gelatin particle agglutination test for serodiagnosis of lepromatous leprosy. AB - A comparative assessment of three serological methods for leprosy diagnosis (the fluorescent leprosy antibody absorption [FLA-ABS] test, the Mycobacterium leprae soluble-extract enzyme-linked immunosorbent assay [ELISA], and the M. leprae particle agglutination [MLPA] test) was carried out. The objective was to identify their performance in clinical and epidemiological diagnosis of leprosy. The study group included 45 lepromatous leprosy patients under treatment. Specificity was > 95% for all three assays, and sensitivity was 95, 58, and 74% for the FLA-ABS test, the MLPA test, and the ELISA, respectively. The only cross reactivity for M. tuberculosis-infected patients was with the soluble-extract ELISA. Although the FLA-ABS test displayed the highest specificity and sensitivity values, it can only be used in well-developed laboratories, and the patient's clinical and epidemiological background must be considered when results are interpreted because the test remains positive after therapeutic success and could be positive for some household contacts. The MLPA test is easier to perform and interpret, and it is adequate for small laboratories and epidemiological studies intended to detect active untreated or irregularly treated leprosy cases. Therefore, the FLA-ABS and MLPA tests are complementary, and both should be used for serodiagnosis of leprosy. PMID- 8501239 TI - Comparison of the VIDAS RSV assay and the Abbott Testpack RSV with direct immunofluorescence for detection of respiratory syncytial virus in nasopharyngeal aspirates. AB - The sensitivity and accuracy of the VIDAS RSV assay in testing fresh specimens were 82.7 and 87.1%, respectively, whereas specimens previously frozen at -70 degrees C gave a sensitivity of 96.2% and an accuracy of 95.4%. The sensitivity and accuracy of Abbott Testpack RSV were 92.6 and 91.3% for fresh specimens and 86.8 and 88.1% for frozen specimens. The advantages and drawbacks of the two assays are discussed. PMID- 8501241 TI - Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS. AB - Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro. It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined. On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C. albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6. These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients. PMID- 8501240 TI - New latex reagent using monoclonal antibodies to capsular polysaccharide for reliable identification of both oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus. AB - A new latex agglutination test (Pastorex Staph-Plus, Sanofi Diagnostics Pasteur), consisting of a mixture of latex particles coated with fibrinogen and immunoglobulin G for the detection of clumping factor and protein A and latex particles sensitized with monoclonal antibodies directed to Staphylococcus aureus serotype 5 and 8 capsular polysaccharides, was compared with three commercially available rapid agglutination methods for the identification of 220 isolates of S. aureus (61 oxacillin resistant) and 128 isolates of coagulase-negative staphylococci. The sensitivity for identification of S. aureus was high with the Pastorex Staph-Plus test (98.6%) compared with those of the other tests, which ranged from 91.8 to 84.5%. Test sensitivities for the identification of oxacillin resistant S. aureus were as follows: Pastorex Staph-Plus, 95.1%; Pastorex Staph, 73.8%; Staphyslide, 72.1%; and StaphAurex, 49.2%. PMID- 8501242 TI - Evaluation of the RapID NH system for identification of Haemophilus somnus, Pasteurella multocida, Pasteurella haemolytica, and Actinobacillus pleuropneumoniae isolated from cattle and pigs with respiratory disease. AB - Haemophilus somnus, Pasteurella haemolytica, Pasteurella multocida, and Actinobacillus pleuropneumoniae from cattle and pigs with respiratory disease were used to evaluate the RapID NH system (Innovative Diagnostics, Atlanta, Ga.). Minor modifications of the RapID NH system to include animal source and growth requirements would permit the identification of all isolates tested. PMID- 8501243 TI - Direct polymerase chain reaction for detection of human immunodeficiency virus in blood spot residues on filter paper after elution of antibodies: an adjunct to serological surveys for estimating vertical transmission rates among human immunodeficiency virus antibody-positive newborns. AB - Blood spot residues on filter paper circles from which antibodies have been eluted remain suitable for follow-up polymerase chain reaction to detect human immunodeficiency virus (HIV) provirus. A method has been developed for specimen processing and nested polymerase chain reaction amplification with a single tube. HIV-positive specimens can be detected by simple, direct electrophoresis of amplified material to a single copy of provirus. The procedure is particularly suited for survey purposes to estimate rates of vertical transmission of virus among HIV antibody-positive newborns, in whom virus loads may be low. PMID- 8501244 TI - Zygomycotic necrotizing fasciitis caused by Apophysomyces elegans. AB - A case of necrotizing fasciitis of the anterior abdominal wall caused by the zygomycete Apophysomyces elegans in a healthy male following inguinal herniorrhaphy is reported. The portal of entry of the fungus into the incised skin and subcutaneous tissues was probably through either contaminated surgical sutures or postoperative surgical dressings. Broad, aseptate fungal hyphae were seen in the necrosed tissues with an associated necrotizing vasculitis. Extensive tissue debridements and a low dose of amphotericin B were not successful in controlling the rapid invasion of the tissues by the fungus. PMID- 8501245 TI - Two-site comparison of broth microdilution and semisolid agar dilution methods for susceptibility testing of Cryptococcus neoformans in three media. AB - This study evaluated the inter- and intralaboratory agreement between results of the semisolid agar dilution and broth microdilution methods of antifungal susceptibility testing of Cryptococcus neoformans. Three media were tested in two laboratories. The drugs tested were amphotericin B, flucytosine, itraconazole, fluconazole, and Schering 39304. Analysis by kappa statistics revealed good agreement between the laboratories for the two methods. The highest level of inter- and intralaboratory agreement was observed in RPMI 1640 with L-glutamine followed by Eagle's minimum essential medium and yeast nitrogen broth. The broth microdilution method appears more suitable than the semisolid agar dilution method for testing cryptococci because of its ease in performance, cost, and simplicity. PMID- 8501246 TI - Evaluation of a 2-minute anti-human immunodeficiency virus (HIV) test using the autologous erythrocyte agglutination technique with populations differing in HIV prevalence. AB - A total of 1,800 blood specimens (1,000 from healthy blood donors, 300 from patients with sexually transmitted disease, and 500 from intravenous drug users) were simultaneously tested with anti-human immunodeficiency virus enzyme-linked immunosorbent assay (ELISA) kits and a newly developed 2-min test for anti-human immunodeficiency virus based on the principle of autologous erythrocyte agglutination (AGEN Biomedical Limited). We found that AGEN's rapid test was as sensitive and specific as the other ELISA kits. PMID- 8501247 TI - Conventional identification characteristics, mycolate and fatty acid composition, and clinical significance of MAIX AccuProbe-positive isolates of Mycobacterium avium complex. AB - A total of 145 isolates belonging to the Mycobacterium avium complex (MAC) were tested with commercial acridinium ester-labeled DNA probes (AccuProbe, Gen Probe). M. avium and M. intracellulare probes reacted with 102 and 36 isolates, respectively. The remaining seven isolates were clearly positive with the new probe, designated MAIX. Thus, the combined sensitivity of M. avium and M. intracellulare probes was 95.2%. The MAIX probe improved the sensitivity up to 100%. The MAIX probe also reacted with all M. avium (n = 20) and M. intracellulare (n = 20) isolates tested. Three of the seven MAIX-positive isolates were considered clinically significant. We conclude that the new MAIX probe should be used, in addition to M. avium and M. intracellulare probes, for the identification of MAC isolates. Our results also suggest that the probe may be used alone to cover the whole MAC when species differentiation is not required. PMID- 8501248 TI - Development of an enzyme-linked immunosorbent assay method for typing and quantitation of Klebsiella pneumoniae lipopolysaccharide: application to serotype O1. AB - We describe a method for the typing and quantitation of Klebsiella pneumoniae serotype O1 lipopolysaccharide (LPS) based on inhibition in an enzyme-linked immunosorbent assay of a reaction of known O1 LPS antigen and anti-O1 antibody by unknown LPS extracts. Serotype O1 was found in 32% of the 124 K. pneumoniae clinical isolates tested, showing that this serotype is frequent among the eight O serotypes which have been described previously. PMID- 8501249 TI - Mycobacteria in stool specimens: the nonvalue of smears for predicting culture results. AB - A previous recommendation suggests that stool be cultured for mycobacteria only if the smear is positive. We have correlated smear and culture results of 2,176 stool specimens submitted for mycobacterial culture. The sensitivity, specificity, and positive and negative predictive values for smears to predict culture results are 34, 99, 90, and 87%, respectively. We recommend that the stool smear not be used as a screening technique to decide which specimens from at-risk patients should be cultured because it lacks the necessary sensitivity. PMID- 8501250 TI - Antigenic and genetic characterization of Borrelia species isolated from Ixodes persulcatus in Hokkaido, Japan. AB - Ten characteristic strains of spirochetes (HT2, HT7, HT10, HT15, HT17, HT19, HT20, HT22, HT32, and HT59) isolated from Ixodes persulcatus adult ticks in Hokkaido, Japan, were selected and analyzed by polyacrylamide gel electrophoresis, with monoclonal and polyclonal antibodies, and by pulsed-field gel electrophoresis. The protein profiles of the borrelial isolates were variable and markedly different from that of the type strain Borrelia burgdorferi B31. The 41-kDa flagellin protein was present in all isolates, but the outer surface protein A (OspA) was absent in four isolates (HT15, HT2, HT20, and HT32). The molecular weights of the OspA proteins in six isolates were found to differ from one isolate to another. No two isolates examined had the same plasmid profile. These findings show the antigenic and genetic heterogeneity of the Japanese isolates, and some isolates are strikingly different from North American, European, and Asian strains. PMID- 8501251 TI - Isolation of Shigella dysenteriae serotypes 11, 12, and 13 from patients with diarrhea in Bangladesh. AB - Nine isolates of bacteria biochemically resembling Shigella dysenteriae but not belonging to the 10 recognized serotypes were isolated from patients with diarrhea in Bangladesh. Further studies suggested that two, one, and six isolates belonged to the recently recognized S. dysenteriae serotypes 11, 12, and 13, respectively. PMID- 8501252 TI - Detection of immunoglobulin A in urine specimens from children with Campylobacter associated diarrhea by a chemiluminescent indicator-based western immunoblot assay. AB - A Western blot (immunoblot) assay was used to detect Campylobacter-specific immunoglobulin A in urine. Acute-phase urine samples from six children with Campylobacter diarrhea had titers ranging from 2 to 8. The highest titer was detected 4 days postonset. Campylobacter-specific immunoglobulin A was undetectable in the paired convalescent-phase specimens and urine samples from three control children. PMID- 8501254 TI - Isolation of Nocardia asteroides on buffered charcoal-yeast extract agar. PMID- 8501253 TI - Bacterial clump formation at the surface of liquid culture as a rapid test for identification of enteroaggregative Escherichia coli. AB - Forty-one strains of enteroaggregative Escherichia coli formed clumps visible as a scum at the surface of a Mueller-Hinton broth shaker culture. Sixty-one control strains of E. coli did not. Scum formation is a simple, rapid, and inexpensive test for the identification of enteroaggregative E. coli. PMID- 8501255 TI - Orbital malignant peripheral nerve sheath tumors. Treatment with surgical resection and radiation therapy. AB - A series of three patients with primary orbital malignant peripheral nerve sheath tumors (MPNST) is presented. Two of our patients who were treated with surgery and postoperative radiotherapy are free of tumor recurrence. The third patient showed a good response to radiation therapy. While surgical excision remains the mainstay of therapy, our patients demonstrate the usefulness of adjuvant radiation therapy in this condition. PMID- 8501256 TI - Ocular ethambutol toxicity: is it reversible? AB - Delayed onset ocular ethambutol toxicity is usually considered to be reversible following prompt withdrawal of the drug. However, in a series of seven consecutive patients with severe visual deficit due to ethambutol toxicity, only 42.2% (3 of the 7 patients) achieved a visual recovery of better than 20/200 after an average follow-up of 8.3 +/- 2.1 months after stoppage of the drug. On fluorescein angiography, three cases (42.2%) progressed to optic atrophy during the follow-up with permanent visual damage. There were no predisposing or risk factors to contribute toward the poor visual gain. In this background, we recommend discontinuation of ethambutol from the antituberculous regimen. As an additional sidelight, the value of visually evoked potential in the monitoring of patients on ethambutol, especially in cases with early periaxial neuritis, has been emphasised. PMID- 8501257 TI - Visual loss as the initial presentation of nasopharyngeal carcinoma. AB - Eye symptoms and cranial nerve involvement are rather common in nasopharyngeal carcinomas, but early invasion of the optic nerve is very rare. Two cases of nasopharyngeal carcinoma that presented initially with visual loss are reported. PMID- 8501258 TI - Sudden blindness and total ophthalmoplegia in mucormycosis. A clinicopathological correlation. AB - A case of rhino-orbitocerebral mucormycosis is presented, illustrating the serious nature of this disease. Clinical features and their pathological correlations are demonstrated. The need for a high index of clinical suspicion, and an early biopsy of the affected area is emphasized so that the benefits of early diagnosis and therapy may be gained. PMID- 8501259 TI - Transient cortical blindness due to hypertensive encephalopathy. Magnetic resonance imaging correlation. AB - Striking reversible signal intense magnetic resonance imaging (MRI) lesions were observed in the occipital cortex of a 16-year-old girl who presented with an attack of transient cortical blindness as the initial manifestation of hypertensive encephalopathy (HTE). The lesions were seen to best advantage on T2 weighted imaging and were not visible on computed tomography (CT). It is proposed that such occipital lobe MRI lesions likely reflect extravasation of fluid and proteins across the blood brain barrier, damaged as a consequence of cerebral autoregulation failure. PMID- 8501260 TI - Tonic pupil in lymphomatoid granulomatosis. AB - Tonic pupil is due to a lesion of orbital parasympathetic neurons in the ciliary ganglion or short ciliary nerves (1). Precise etiology of the condition remains obscure. In the case described here, development of "tonic pupil" was followed by systemic features typical of lymphomatoid granulomatosis, and diagnosis was confirmed by histology of the skin rash. This case underlines the heterogeneity of the causes of tonic pupil. Vascular occlusion can be a possible mechanism in the pathogenesis of tonic pupil. PMID- 8501261 TI - The four-meter confrontation visual field test. AB - Confrontation visual fields have limited value in testing paracentral vision. We have used a four-meter confrontation test for several years at the Mayo Clinic for screening of the central field. This test can identify paracentral scotomas and macular sparing in a homonymous hemianopia. The optics of this technique parallel those of the two-meter tangent screen examination in which a scotoma is greatly enlarged by doubling the test distance. Although in common usage by some neuro-ophthalmologists, this simple technique is useful as an office screening device for evaluating paracentral vision. PMID- 8501262 TI - Linear nevus sebaceous syndrome. AB - The pathologic terms hamartoma, choristoma, nevus, and phakoma often are confused. We discuss them in relation to a patient with the linear nevus sebaceous syndrome who had a large limbal mass that grew unusually rapidly and was excised. Histopathologic examination showed that it was a complex choristoma composed of lacrimal gland, adipose tissue, and myxomatous tissue. The latter has not been described previously in this disorder. This neuro-oculocutaneous syndrome has been considered one of the phakomatoses. PMID- 8501263 TI - Free air in the cavernous sinus as an incidental finding. AB - Free air within the cavernous sinus was discovered incidentally on a computed tomographic (CT) scan. We suggest that air bubbles were introduced inadvertently when contrast material was injected just prior to CT scanning. On a repeat CT scan 16 days later, the air had disappeared. PMID- 8501264 TI - Unilateral conjugate gaze palsy due to a lesion of the abducens nucleus. Clinical and neuroradiological correlations. AB - We report a case of left-sided horizontal gaze palsy, ipsilateral adduction weakness, and left peripheral facial weakness, all of which indicate the lesion in the left median pontine tegmentum. The enhanced MRIs revealed a discrete left median pontine tegmental lesion, involving the abducens nucleus, MLF, and facial nerve knee. This lesion spared the area of the left PPRF. Among these structures, the area of the abducens nucleus seems to be responsible for the unilateral horizontal gaze palsy. We are not aware of any previous precise neuroradiological documentation of unilateral paralysis of conjugate gaze due to a lesion of the abducens nucleus by sagittal and horizontal MRIs. PMID- 8501265 TI - Quantitative longitudinal assessment of saccades in Huntington's disease. AB - While participating in a controlled study of baclofen as protective therapy, 39 Huntington's disease (HD) patients underwent measurements of horizontal saccade latency and velocity, repeated longitudinally over a 2-year period. Significant worsening of saccade latency and of mean velocity was detected in untreated patients. Although individual variation was great, initial velocity impairment was found to be more prominent in younger patients. Factors are identified that may affect the rate of decline in supranuclear oculomotor function, including age and the severity of illness at the time of initial assessment. We propose that serial quantitative measurement of saccade performance is a useful clinical marker of the rate of disease progression against which the efficacy of treatments may be tested. PMID- 8501266 TI - A comparative study of tear secretion in blepharospasm and hemifacial spasm patients treated with botulinum toxin. AB - In the neuro-ophthalmology clinic at St. Vincent's Hospital, Melbourne, 57 patients with blepharospasm and 50 patients with hemifacial spasm were treated with botulinum toxin. Schirmer tear tests were conducted on all the patients prior to each treatment and at 1 week following treatment where possible. The results were compared with a control group of 107 patients selected by age and sex. The blepharospasm patients were found to have a significantly lower tear secretion than that of the control group, using the Mann-Whitney test (median = 3.5 mm, compared with median-11.0 mm, p < .0001). This did not improve following treatment. The patients with hemifacial spasm did not have significantly different tear secretion from that of the control group (t = 1.0, p > .05). To investigate whether there was any relationship between the symptoms and the result of the Schirmer test, a survey was also conducted on the patients with blepharospasm and hemifacial spasm regarding symptoms, frequency, and type of drops/ointment used. PMID- 8501267 TI - Saccades. PMID- 8501268 TI - Sudden visual field constriction associated with optic disc drusen. AB - We report two patients with optic disc drusen who suffered sudden, concentric constriction of the visual field. Visual acuity remained normal. The involved discs showed no swelling, hemorrhage, or other evidence of anterior ischemic optic neuropathy. We are unable to explain the mechanism or the pattern of visual field loss in these unusual cases. PMID- 8501269 TI - The role of supragingival plaque in the control of progressive periodontal disease. A review. AB - Levels of supragingival plaque and calculus have been related to progressive periodontal disease, and control of supragingival plaque in conjunction with professional tooth cleaning subgingivally forms the basis for the management of progressive periodontal disease. However, the contribution towards the management of progressive periodontal disease brought about by supragingival plaque control alone is not clear. There are studies which address, directly or indirectly, the contribution of supragingival plaque control alone towards the management of progressive periodontal disease. The effects of supragingival plaque control alone have been evaluated clinically, histologically and microbiologically, and taken together, the evaluations suggest that these effects may not be as marked as when professional subgingival tooth cleaning is also performed. These studies, however, given the patterns of periodontal disease found in adults in many communities, can form the basis for advocating high individual levels of supragingival plaque control as a community measure in the management of periodontal disease. Further long-term investigations into this approach may be warranted. PMID- 8501270 TI - The effect of oral irrigation with a magnetic water treatment device on plaque and calculus. AB - Calculus formation on tooth surfaces is analogous to the formation of lime and scale deposits in plumbing. Magnetic water devices have been shown to significantly reduce scale deposits in industry; therefore an oral irrigator with a magnetic water device may have a similar effect on calculus. To test this hypothesis, a double-blind clinical study was established using 64 irrigators, 30 of which had their magnetic devices removed. 54 patients with heavy supragingival calculus were given irrigators at random after prophylaxis. Instructions were given to irrigate twice a day, particularly the lower 6 anterior teeth. The patients were also told not to floss these 6 teeth which were to be the study teeth. They were examined after 3 months and measurements were taken of the accretions adhering to the study teeth. No attempt was made to determine whether the adhering material was hard or soft so it must be assumed that at least some of the measured material was also plaque. The measurements of the group using an irrigator with a magnetic device showed a 44% greater reduction in calculus volume (p < 0.0005) and a 42% greater reduction in area (p < 0.0001) over the group using an unmagnetized irrigator. There appears to be a statistically significant difference in supragingival accretion volumes between conventional irrigation and using an irrigator with a magnetic water treatment device. PMID- 8501271 TI - Scanning electron microscopic observations of early plaque formation in vivo on enamel specimens treated with delmopinol. AB - The aim of this double blind, cross-over, scanning electron microscopic (SEM) study was to compare the effect of topical application of 0.5% delmopinol HCl (aqueous solution) with placebo on early supragingival plaque formation on enamel specimens attached to a maxillary premolar. 3 subjects underwent 2x (placebo and delmopinol treatment, respectively) 7 treatment periods (1/2, 1, 2, 8, 24 hours; 3, 7 days) of undisturbed dental plaque accumulation, during which 2 ml of placebo and delmopinol HCl 0.5%, respectively, were applied topically to all teeth 2x daily. At the end of each period, the specimen was retrieved and processed for SEM. For the specimens obtained after 24 h or less, the number of visible micro-organisms was estimated. For the 3- and 7-day specimens, the area covered by plaque was calculated planimetrically. Large inter-individual differences were observed in the number of bacteria attaching during the first 24 h, with apparently no major differences between delmopinol and placebo. 1 subject showed a bacterial colonization predominated by curved rods throughout the first 8 h. Compared to placebo, the area of the specimens covered by plaque was reduced after 3 and 7 days of delmopinol use, with coccoid cells as the predominant morphotype. Plaque maturity, characterized by the appearance of corncob formations and high numbers of different morphotypes, was not observed on the delmopinol specimens, in contrast to the placebo specimens. The study shows that topical application of 0.5% delmopinol HCl delays and interferes with dental plaque maturation. PMID- 8501272 TI - The effect of a triclosan-containing dentifrice on established plaque and gingivitis. AB - The aim of the present clinical trial was to study the effect on existing plaque and gingivitis of an oral hygiene regimen which utilized a dentifrice which contained triclosan. 120 subjects were recruited for the trial. They were examined for plaque and gingivitis using the criteria of (i) the Turesky modification of the Quigley & Hein plaque index and (ii) the Loe & Silness gingival index. Plaque and gingivitis were assessed in all parts of the dentition and at 6 location points around each tooth. Following a baseline examination, the subjects were stratified in 2 balanced groups based on age, plaque and gingivitis scores. The subjects were randomly assigned to the following treatment: 1 test group used a dentifrice containing triclosan/copolymer/fluoride and 1 control group used a traditional fluoride containing dentifrice. The participants were given the assigned dentifrice and a soft-bristled toothbrush for home use. They were instructed to brush their teeth in the morning and in the evening for one minute each time. They were reexamined 6 weeks, 3 and 6 months after the baseline examination. The findings from the re-examinations revealed that an oral hygiene regimen which utilized a dentifrice which contained triclosan/copolymer significantly reduced pre-existing plaque and gingivitis above what was accomplished by a traditional fluoride containing dentifrice. The improvement of the gingival conditions occurred in all parts of the dentition and at all tooth surfaces and units. In addition, the present data support the hypothesis that triclosan may induce alterations in the quality of existing plaque. PMID- 8501273 TI - The effect of a mouthrinse based on nisin, a bacteriocin, on developing plaque and gingivitis in beagle dogs. AB - The aim of this study was to evaluate the effect of nisin, an antimicrobial peptide, on the development of plaque and gingivitis in beagle dogs when compared with 0.12% chlorhexidine and a placebo. 16 female beagle dogs 1 year of age were brought to optimum gingival health by scaling, root planing and polishing. At the conclusion of the pretreatment phase, the dogs were divided into 4 groups for the application of the test agents and were placed on a plaque promoting diet of Purina Dog Chow softened with water. Test agents included 100 micrograms/ml nisin and 300 micrograms/ml nisin formulated in a vehicle containing 1 mM NaEDTA; negative control comprised of exactly the same formulation but omitting nisin; and 0.12% chlorhexidine as Peridex. Throughout the treatment period, formulations were applied 2x daily to premolar teeth in each quadrant for 1 min using a Monojet syringe. The development of plaque and gingivitis was monitored at 15, 27, 39, 53, 74 and 88 days during the treatment phase using standard measurements of gingival index, plaque index, stain index and bleeding to probing. Throughout the treatment phase, plaque accumulation increased in all groups, but the rate of plaque build-up was less in groups treated with either nisin or chlorhexidine formulations compared with the placebo treated group. The gingival index of dogs in all groups increased throughout the study period. However, from day 27 onward, the groups receiving nisin had lower gingival index scores than did the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501274 TI - Gingivitis, plaque accumulation and plaque composition under long-term use of Meridol. AB - The effectiveness of amine fluoride and stannous fluoride in the prophylaxis of caries and gingivitis is well-known from the literature. The aim of this study was to assess whether these agents could be recommended for long-term use. Under conditions of a clinical double-blind study, the influence of an amine/stannous fluoride rinse on gingivitis, plaque accumulation and the composition of the supragingival plaque was tested over a period of 7 months. 102 persons with signs of chronic gingivitis participated in the study. Gingival indices (GI, SBI) and plaque indices (PlI, API) were recorded at baseline, after 3.5 and 7 months. The composition of the supragingival plaque was evaluated by dark-field microscopy. During the 7 months, the GI decreased in the test group from 1.36 to 0.95, and the SBI from 52.0% to 29.3%. The PlI fell from 1.17 to 0.68, and the API from 61.3% to 50.6% (p < 0.001). No significant changes were recorded in the control group. In the test group, the proportion of cocci in the plaque increased from 58.4% to 68.9% (p < 0.001) while the proportion of rods and other plaque bacteria underwent a significant decrease (p < 0.001). The microflora was stable in the control group throughout the study period. No side-effects of the drug were reported by the probands. The results suggest that long-term use of the amine/stannous fluoride rinse is of benefit to gingival health. PMID- 8501275 TI - Periodontal disease experience in adult long-duration insulin-dependent diabetics. AB - The aim of this study was to analyse periodontal disease experience in 40- to 70 year-old, sex-matched insulin-dependent diabetics and non-diabetics. The study involved 83 diabetics and 99 non-diabetics. The clinical and radiographic examination comprised recordings of number of teeth, presence of plaque, gingival conditions, probing pocket depth and alveolar bone level (main variable). Diabetics aged 40 to 49 years had more periodontal pockets > or = 6 mm and more extensive alveolar bone loss than non-diabetics in the same age-group. There was also a significantly higher number of subjects belonging to classification groups with severe periodontal disease experience among diabetics in that age-group. In the age-groups 50-59 and 60-69 years, no major differences were found. The disease duration in these 3 age groups was 25.6 years, 20.5 years and 18.6 years, respectively, and the age of onset thus appears to be an important risk factor for future periodontal destruction. PMID- 8501277 TI - Dentin demineralization. The effects of citric acid concentration and application time. AB - Preliminary work has shown that the rate of dentin demineralization increases with increasing concentrations of citric acid. This rate subsequently diminishes at much higher concentrations. The purpose of this study was to more precisely identify the citric acid concentration which produces peak dentin demineralization and to determine if this demineralization process is time dependent. Flat dentin surfaces were prepared on the buccal and lingual sides of 15 bovine molars. 8 depressions were made in each dentin surface using a #8 round bur in a high-speed handpiece with air-water coolant. Various concentrations of citric acid solutions (weight per cent) were prepared, e.g., 0%, 10%, 20%, 25%, 30%, 35%, 40%, 65% and their respective pH's recorded. 3 microliters of each citric acid solution were placed in individual depressions on the dentin surfaces and left undisturbed for 1, 2 or 3 min. Cotton pellets were used to soak up the citric acid solution, along with any dissolved calcium, and were subsequently placed in 10 ml of 18 Me omega water. The parts per million calcium found in each water sample were determined using atomic absorption spectrophotometry. Peak dentin demineralization for 1-, 2- and 3-min application times occurred at 30% (pH = 1.55), 25% (pH = 1.62) and 25% (pH = 1.62) citric acid concentrations/(pH), respectively. Dentin demineralization was found to be time-dependent for all citric acid solution concentrations. The clinical significance of these findings is discussed. PMID- 8501276 TI - The effect of subgingival debridement on periodontal disease parameters and the subgingival microbiota. AB - The aim of the present investigation was to analyse the effect of subgingival scaling and root planing in subjects who prior to treatment exercised meticulous supragingival plaque control. 300 subjects were examined at baseline and after 1 and 2 years without treatment. After the year 2 examination, 62 subjects were randomly selected for therapy. They were given detailed instruction in proper self-performed toothcleaning measures and were carefully monitored during the subsequent 2 years. Following the year-4 examination, 2 quadrants, 1 maxillary and 1 mandibular in each subject, were randomly selected for additional therapy. The teeth in the selected quadrants were exposed to subgingival scaling and root planing. The subgingival therapy was repeated until a site no longer bled on gentle probing. This basic therapy was completed within a 2-month period. All subjects were re-examined after another 12-month interval. The examinations at year 4 and 5 included assessment of plaque, gingivitis, probing pocket depth and analysis of samples obtained from the subgingival microbiota at 134 selected sites. The findings from the present study demonstrated: (i) that subgingival scaling and root planing were effective in eliminating subgingival plaque and gingivitis; (ii) that professional therapy resulted in a pronounced reduction of probing depth at sites which at year 4 had a probing depth > 3 mm; (iii) that in non-scaled quadrants, the extension of self-performed plaque control resulted in a continued improvement of the periodontal conditions at sites which at year 4 were < 5 mm deep. PMID- 8501278 TI - The effects of orthodontic tooth movement on the glycosaminoglycan components of gingival crevicular fluid. AB - In this study, gingival crevicular fluid (GCF) was collected from around a canine tooth, in children, before and during orthodontic tooth movement. The aim was to identify and quantify the glycosaminoglycan (GAG) components of GCF and relate them to tooth movement, gingival inflammation, plaque accumulation, pocket probing depth and GCF volume recorded at the site of sampling. GAG in GCF samples, collected for a 15-min period into microcapillary tubes, were separated electrophoretically, stained with Alcian blue and quantified using a laser densitometer. 2 GAG components of hyaluronic acid (HA) and chondroitin sulphate (CS) were identified. The increase in GCF volume during orthodontic tooth movement was only partly due to increased gingival inflammation. GAG levels varied with different types of orthodontic tooth movement. In GCF, levels of CS, in particular, may reflect the changes in the deeper periodontal tissues which could be monitored during orthodontic tooth movements. PMID- 8501279 TI - Dr. Goldstein's selection and interpretation of psychological literature pertaining to the benefits of physical attractiveness. PMID- 8501280 TI - Ethics in dental research: my views. PMID- 8501281 TI - The distribution of saliva and sucrose around the mouth during the use of chewing gum and the implications for the site-specificity of caries and calculus deposition. AB - Over a 20-minute period, subjects expectorated 8 samples of whole saliva (EWS) while chewing gum. Flow rates were calculated, and sucrose was analyzed in these samples as well as in saliva collected on filter paper strips from different tooth surfaces. Salivary film velocity (SFV), based on a 0.1-mm-thick film, was estimated from the clearance half-times of KCl in agarose disks positioned in different regions of the mouth. Salivary flow rate peaked at 5.1 mL/min in the first min but fell to about 1.25 mL/min by the end of the 20 min of gum-chewing. In contrast, flow rate when subjects sucked sour lemon drops averaged about 5.3 mL/min throughout the 20-minute period. The mean salivary sucrose concentration during gum-chewing peaked in the second min at 384 mmol/L (13.1%) but had fallen to 14 mmol/L by the 15-20-minute time interval. The sucrose concentrations on the palatal surfaces of the upper incisors and the facial and lingual surfaces of the lower molars were not significantly different from that in EWS but were much lower on the facial surfaces of the upper incisors and molars, and on the lingual surfaces of the lower incisors. When flow was unstimulated, SFV was 0.8-1.0 mm/min on the facial surfaces of the upper incisors and lower molars but about 5 8 mm/min on the facial surfaces of the upper molars and on the lingual surfaces of the lower incisors and molars.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501282 TI - Simultaneous caries induction and calculus formation in rats. AB - Weanling specific pathogen-free Osborne-Mendel rats were fed a high-calcium, high phosphorus diet with various levels of sucrose and inoculated with Streptococcus sobrinus strain 6715-13WT and Actinomyces viscosus strain OMZ-105 in order to determine whether calculus and caries could develop simultaneously. Rats consumed diets designated RC-16-5, RC-16-25, or RC-16-50 which partially replaced the corn starch component with progressively higher levels of sucrose, thus, to 5, 25, or 50% sucrose. In general, bacterial recoveries of A. viscosus declined with higher sucrose content of the diet, but a pattern of recovery for S. sobrinus was less clear with respect to dietary sucrose. S. sobrinus, however, was recovered at higher percentages from the tooth surface flora at the later two of three sampling dates. Most calculus--identified by the brittle quality, staining characteristics, and apatitic x-ray diffraction patterns of tooth surface deposits--was formed on the maxillary molars, and most carious lesions occurred on mandibular molars. While there was minimal association of the calculus score with the amount of sucrose in the diet, calculus scores increased greatly from 23 to 43 days after infectious challenge. Caries scores, of both fissure and smooth surfaces, by contrast, increased in a dose-response fashion with increasing dietary sucrose and with time. It is thus possible to induce calculus formation and caries simultaneously in specific pathogen-free Osborne-Mendel rats consuming a high-calcium and -phosphorus diet conducive to calculus formation and containing sucrose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501283 TI - Comparison of three different methods for measurement of plaque-pH in humans after consumption of soft bread and potato chips. AB - Three different techniques for measurement of plaque-pH--the sampling, the microtouch, and the telemetric methods--were compared after subjects had consumed different starch products. Ten volunteers, equipped with partial lower prostheses, incorporating a miniature glass pH electrode, refrained from toothbrushing for 3 days. Four products were tested: (1) soft bread, (2) potato chips, (3) 5% starch, and (4) 5% sucrose. The pH of plaque was measured for 45 min by means of all three of the methods. The results showed that the mean pH at 10 min was 1.5 units lower with the telemetric than with the sampling method and 1.0 unit lower with the telemetric than with the microtouch method. Relatively small differences were found among the effects of the four test products for all three methods, with the clearest distinctions among the pH curves being with the microtouch and telemetric methods. The main conclusions from the present investigation are: (1) that there were large differences in pH levels measured with the sampling, the microtouch, and the telemetric methods, even though they ranked the test products in about the same order, and (2) that the two starchy foods, bread and potato chips, were both easily fermented by dental plaque. PMID- 8501284 TI - Power spectral analysis of temporomandibular joint sounds in asymptomatic subjects. AB - Very little has been done to quantify temporomandibular joint (TMJ) sound amplitudes and background noise and to determine the spectrum from healthy TMJs. Thus, the aim of this study was to record acoustically the sounds emitted by healthy TMJs with and without mandibular movements, for determination of baseline spectra. TMJ sounds were recorded bilaterally from 40 subjects with healthy joints by means of a self-developed recording system using miniature capacitor microphones inserted into the earpieces of a medical stethoscope placed in the meatus of the auditory canal. The recordings were performed without mandibular movements and during three consecutive opening and closing movements. The signals were high-pass-filtered at 50 Hz, low-pass-filtered at 2 kHz, and analyzed by fast Fourier transform computation on a 1024-point window (fs = 5 kHz). The linearly weighted average baseline spectrum recorded without motion showed maximum values of 31 dBSPL (sound pressure level) with a standard error of +2 to 3 dB. The linearly weighted average movement spectrum had a peak of 66 dBSPL at 156 Hz and decreased almost linearly by about 40 dB/decade to 25 dBSPL at 2000 Hz with a standard error of +/- 2 dB. Thus, the TMJ sound spectrum of mandibular movements in asymptomatic subjects differed at low frequencies by up to 35 dB from the baseline spectrum in absence of motion. PMID- 8501285 TI - The effect of an occlusal stabilization splint and the mode of visual feedback on the activity balance between jaw-elevator muscles during isometric contraction. AB - The aim of the present study was to gain an insight into the influence of a vertical bite-rise (clenching in intercuspal occlusion vs. clenching on an occlusal stabilization splint), the mode of visual feedback (VF; obtained from the compound masseter signal, from the compound anterior temporalis signal, or from the compound signal of both masseter and anterior temporalis muscles) and the EMG clenching level (10% MVC and 50% MVC) on the muscle balance between the masseter and the anterior temporalis muscles. The muscle balance was quantified as the logarithmic value of the ratio between the summated mean rectified EMG activity of the masseter muscles and this activity of the anterior temporalis muscles. The muscle balance was influenced significantly by the mode of VF (p < 0.01), the muscle balance shifting toward the group of muscles from which VF was obtained. When VF was obtained from the masseter muscles, a decrease in the anterior temporalis EMG activity was observed when the vertical dimension was increased (p < 0.05-0.01). When VF was obtained from the anterior temporalis muscles, the activity of the masseter muscles was raised with respect to that of the anterior temporalis muscles during clenching with a vertical bite-rise (p < 0.05-0.01). When VF was obtained from both groups of muscles, the masseteric EMG activity increased, whereas the anterior temporalis EMG activity decreased. Hence, regardless of the mode of VF, a relatively lower activity level of the anterior temporalis muscles was achieved after insertion of an occlusal stabilization splint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501286 TI - An epidemiological assessment of the chronological distribution of dental fluorosis in human maxillary central incisors. AB - The objectives of this study were: (1) to develop and test a new index, the Chronological Fluorosis Assessment (CFA) Index, for measuring variation in the chronological distribution and intensity of dental fluorosis, and (2) to determine whether the new index was sufficiently sensitive for detection of a decline in dental fluorosis corresponding to the reduction in the waterborne fluoride level in Hong Kong. According to the CFA Index, the cervical, middle, and incisal third divisions of the labial surface of a maxillary central incisor crown are each classified into one of six categories of an ordinal scale of fluorosis. Data from 1295 life-long resident Hong Kong Chinese children exposed to known water fluoride concentrations were analyzed. Fluorosis declined from incisal to cervical in 41% of cases, and a reverse gradient was apparent in 29%. Overall, fluorosis intensity was higher on incisal thirds than on both middle and cervical thirds. However, when tooth thirds were regrouped according to common 16 month developmental periods, in order to control for time-related variation in fluoride concentration, the incisal-middle difference was of reduced statistical significance, and both the incisal-cervical and the middle-cervical differences became insignificant. A regression analysis of CFA Index on cohort indicated a significant cohort-related fluorosis decrease, in relation to cervical, middle, and incisal tooth thirds. It was concluded (1) that fluorosed enamel which forms in chronological sequence tends toward a uniform intensity, and (2) that the new index was sufficiently sensitive for a decline to be measured in dental fluorosis in Hong Kong. PMID- 8501287 TI - Agreement among dentists' recommendations for restorative treatment. AB - Differences among dentists in their decisions to recommend treatment have been studied principally at a "macro" level by examinations of variations in dentists' treatment recommendations for individual patients, or for patients aggregated to the practice level. If reasons for these differences are to be understood, however, a "micro" level examination of differences in dentists' decisions to recommend treatment for individual teeth is necessary. Extent of agreement to recommend treatment among dentists was explored for 1187 teeth in 43 patients. Each tooth was examined by a mean of 6.6 general practitioners. A modified reliability index and distributions of raw levels of agreement were used for quantification of agreement rates across an incomplete cross-classification for practitioners and patients. Overall inter-dentist reliability in recommending individual teeth for treatment was moderate, p = 0.62. Among unrestored teeth with no clinically evident caries, as judged by an independent experienced evident caries, as judged by an independent experienced examiner, reliability in treatment recommendations due to caries was fair, p = 0.51. Reliability was lowest for recommendations concerning previously restored teeth, p = 0.43. Among all teeth receiving at least one recommendation for treatment, only 22% received a unanimous recommendation. Over one-half of all instances of lack of agreement resulted from a single dentist's recommendation differing from those of all other dentists examining the tooth. The results suggest that much of the variation in dentists' practice profiles is due to basic differences in decisions to recommend treatment for individual teeth with specific conditions, and that the presence of previous restorations seems to magnify these differences. PMID- 8501288 TI - Effects of pH, potassium, magnesium, and bacterial growth phase on lysozyme inhibition of glucose fermentation by Streptococcus mutans 10449. AB - The effects of physiological (saliva and plaque fluid) concentrations of potassium and magnesium and growth phase on lysozyme inhibition of glucose fermentation by S. mutans 10449 were investigated. Glucose fermentations were carried out in a pH-stat at pH 7.0 or 5.5. Cells were at least two times more sensitive to lysozyme in the early-to-middle exponential phase compared with the stationary phase. S. sobrinus 6715 exhibited three-fold greater lysozyme resistance than S. rattus BHT or S. mutans 10449. The concentration of potassium which reduced lysozyme inhibition of S. mutans 10449 fermentation by 50% was 0.2 and 10 mmol/L for stationary and exponential phase cells, respectively. Corresponding values for magnesium were < or = 0.01 and 0.50 mmol/L. Potassium and magnesium exhibited little pH dependence in their reduction of lysozyme inhibition of fermentation by exponential- or stationary-phase S. mutans 10449. The results suggest that: (i) lysozyme interaction with stationary-phase cells involves more non-inhibitory modes than with exponential-phase cells, and (ii) lysozyme may be more effective as an antibacterial agent in saliva than in plaque fluid. PMID- 8501289 TI - Fluoride and iron concentrations in the enameloid of lower teleostean fish. AB - Our quantitative elemental analyses with the electron microprobe indicated that the fluoride and iron concentrations in the enameloid of bony fish are related to the phylogeny of fish. The enameloid of some bony fish with high F also contained high Fe. In order to clarify the phylogenetic significance of such a peculiar dual deposition of F and Fe into developing enameloid, quantitative electron microprobe analyses of these elements were made on the teeth of taxonomically lower teleosts. There were significantly different trends of F and Fe concentrations in the enameloid among various forms of lower teleosts. In the Osteoglossiformes, the enameloid of the osteoglossid species contained very low levels of F and Fe, whereas in the single representative of the Mormyroidei, the F was very low but Fe was very high. In the Elopomorpha, the enameloid of the elopiform species contained a medium level of F and high Fe, and that of the anguilliform high levels of F and Fe. In the Salmoiformes, the salmonid species had medium F and high Fe, and in a species of the Esocidae, high F and high Fe levels were found. The stomiiform fish exhibited levels of medium and high F and high Fe. The results of the present study and our previous investigations made on archaic non-teleostean and various teleostean fish indicate that the mechanisms of F and Fe concentrations into developing enameloid are independent of each other, and that the mechanisms of Fe concentration appeared earlier and disappeared later than, or concurrently with, that of the F concentration, in the course of fish evolution. PMID- 8501290 TI - Scanning microradiographic study of the kinetics of subsurface demineralization in tooth sections under constant-composition and small constant-volume conditions. AB - The kinetics of subsurface demineralization of tooth sections has been studied in real-time by scanning microradiography (SMR). Demineralization was carried out: (1) with a large volume of solution buffered to pH = 4 to maintain a constant composition; and (2) in a small constant volume (approximately 3 mL), buffered initially at pH = 4, so that the degree of saturation at the tooth surface increased as the tooth dissolved. At constant composition, the change in lesion depth, Y, with time, T, followed a linear relation, Y = a + bT, for T > 44 +/- 5 h. Before this time, the relation could be approximated by a linear one with different a and b constants. At constant volume, Y = q(1-e-r(T + s)) for all T, where q, r and s are constants. Similar relations, with different constants, were found for the mineral loss per unit area of lesion exposed to acid. These results showed that the process of demineralization under the rather severe conditions used was essentially a surface-controlled process. The change of slope at approximately 44 h and the presence of the constant s in the exponential function were attributed to a change in kinetics after formation of the surface layer. PMID- 8501291 TI - Cytotoxicity and dentin permeability of carbamide peroxide and hydrogen peroxide vital bleaching materials, in vitro. AB - There has been recent concern about the inadvertent exposure of dentin with patent tubules as well as gingiva to bleaching systems containing 10-15% carbamide peroxide or 2-10% hydrogen peroxide for more than a few minutes. The aims of the present study were: (1) to determine the cytotoxicity of dilutions of hydrogen peroxide in cell culture; (2) to measure hydrogen peroxide diffusion from bleaching agents through dentin in vitro; and (3) to determine the risk of hydrogen peroxide-induced cytotoxicity from exposure of dentin to these vital bleaching agents. The 50% inhibitory dose (ID50) of hydrogen peroxide to succinyl dehydrogenase activity in cultured cells was found to be 0.58 mmol/L after 1 h. All bleaching materials demonstrated diffusion of hydrogen peroxide through dentin in an "in vitro pulp chamber" device. The one- and six-hour diffusates of all bleaching agents through 0.5-mm dentin exceeded the ID50 in monolayer cultures. Inhibition of succinyl dehydrogenase activity corresponded to the amount of hydrogen peroxide that can rapidly diffuse through dentin in vitro and reach concentrations which are toxic to cultured cells in less than 1 h. PMID- 8501292 TI - An in vitro and in vivo study of the release of mercury vapor from different types of amalgam alloys. AB - The aim of the in vitro part of the study was to measure the rate of release of mercury vapor from different types of dental amalgam in air, and in air during cyclic dipping into isotonic saline solution or Fusayama solution. The measurements were carried out by means of the Mercollector/Mercometer system, based on atomic absorption spectrophotometry. Both new (age approximately 2 months) and old (age approximately 1.5 years) amalgam specimens were studied. The variations in the rate of release of mercury vapor in air during cyclic dipping into aqueous media were most pronounced during the first day of the 10-day period studied. In air during cyclic dipping into the aqueous media, the conventional amalgam specimens released mercury vapor at lower rates over the whole period than did the dispersed and single-composition types studied. The aim of the in vivo part of the study was to determine the daily release of mercury vapor from amalgam restorations made of alloys of the same types and batches as those used in the in vitro part of the study. A series of measurements was carried out on each of eight subjects before and after amalgam therapy. None of the subjects was occupationally exposed to mercury. The subjects had to follow a standardized schedule for 24 h, where they ate, drank, and brushed their teeth at predetermined times (Berglund, 1990). The amount of mercury vapor released per time unit was measured at intervals of 30-45 min. Samples of urine and saliva were analyzed formercury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501293 TI - An in vitro and in vivo study of toothbrush bristle splaying. AB - The extent to which a toothbrush is worn out, as evidenced by bristle splaying, is an important determinant of cleaning efficacy. In order for this aspect of oral hygiene to be studied, an accelerated means of producing a life-like pattern of bristle splaying was investigated and compared with splaying induced by a human test-panel. Porcelain denture teeth were brushed under a static applied load in a slurry of dentifrice, by means of a revolving "figure 8" motion, for up to 12,000 revolutions. This was found to induce an increase in the degree of splaying (as measured by "wear index") that was well-fitted (R2 = 0.96) by a second-order expression of the form: WI = WIi + Ritj - Ctj2 where WI = wear index, WIi = initial wear index, Ri = initial rate of increase in WI, tj = brushing time measured in either machine revolutions (tr) or weeks of human use (tw), and C = a separate constant for each brushing mode (machine or human panel). The rate of splaying was found to be strongly influenced by the quality of the bristle filament, but not by small differences in toothbrush design. The splaying pattern induced by the machine could not be distinguished visually from that in a set of brushes used at home by human volunteers. A strong correlation was found between the splaying produced by machine-brushing and by a panel who brushed free-style at home for 13 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501294 TI - Fracture toughness of dentin/resin-composite adhesive interfaces. AB - The reliability and validity of tensile and shear bond strength determinations of dentin-bonded interfaces have been questioned. The fracture toughness value (KIC) reflects the ability of a material to resist crack initiation and unstable propagation. When applied to an adhesive interface, it should account for both interfacial bond strength and inherent defects at or near the interface, and should therefore be more appropriate for characterization of interface fracture resistance. This study introduced a fracture toughness test for the assessment of dentin/resin-composite bonded interfaces. The miniature short-rod specimen geometry was used for fracture toughness testing. Each specimen contained a tooth slice, sectioned from a bovine incisor, to form the bonded interface. The fracture toughness of an enamel-bonded interface was assessed in addition to the dentin-bonded interfaces. Tensile bond strength specimens were also prepared from the dentin surfaces of the cut bovine incisors. A minimum of ten specimens was fabricated for each group of materials tested. After the specimens were aged for 24 h in distilled water at 37 degrees C, the specimens were loaded to failure in an Instron universal testing machine. There were significant differences (p < 0.05) between the dental adhesives tested. Generally, both the fracture toughness and tensile bond strength measurements were highest for AllBond 2, intermediate for 3M MultiPurpose, and lowest for Scotchbond 2. Scanning electron microscopy of the fractured specimen halves confirmed that crack propagation occurred along the bond interface during the fracture toughness test. It was therefore concluded that the mini-short-rod fracture toughness test provided a valid method for characterization of the fracture resistance of the dentin-resin composite interface. PMID- 8501295 TI - Curriculum focus: traditional dental education confronts the new biology and social responsibility. AB - The traditional dental education base does not suggest that graduates are prepared only for private general practice. It promises much, much more. It is the beginning of what any graduate may wish or want it to be. In fact it is necessary for new graduates contemplating private practice to seek more in the way of practice management if they plan to be successful in that model. Such is also the case for additional study if one wants to pursue a specialty; further training in the scientific method to undertake research; or further study in education for a teaching career. The predoctoral program promises to be just a beginning, but a sound and sensible beginning. The current foundation model of the predoctoral curriculum continues to serve society and the profession very well. It provides the necessary grounding in the fundamentals of basic medical sciences, clinical biological sciences, and behavioral sciences upon which any graduate can build and pursue a career beyond what is thought to be the traditional role model of the private practice of general dentistry. Faculty members and dental programs can choose, if they desire, to tailor mission statements to reflect a changing emphasis. This could help dental applicants become more thoughtful and self-selective in considering one of many different career options available. Given the emerging demographic profile and trends in needs, the curriculum emphasis could be altered to encourage a change in the balance or proportion of graduates who undertake career options in a postdoctoral experience, in public health, research, teaching, administration, the military, hospital, or specialty practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501296 TI - Traditional patient care model response. PMID- 8501297 TI - The social responsibility model. PMID- 8501298 TI - Response to the social responsibility model: the convergence of curriculum and health policy. PMID- 8501299 TI - The dental scientist model. AB - A case has been presented for strengthening the science-base of the future dentist. Such a development is essential and inevitable and we must plan the changes in the dental education continuum that will facilitate it. Transfer of advanced clinical training to mandatory post-doctoral education will control the economic impact of the change and improve the education of the dentist tomorrow. PMID- 8501300 TI - Response to the dental scientist model. AB - In general, considerable strength and much realism exist in the model as presented by Dr. McHugh. Progress in biological science is central to any scheme anticipating change in medicine, including dental and oral medicine. In my view, there are two weaknesses in his presentation: 1) a perhaps semantic difference with me over whether dentists should be trained as scientists or as individuals who can use science (fact and process); and 2) a substantive difference as to how to reinforce didactic, basic biomedical science in clinical training. PMID- 8501301 TI - A nine year follow-up survey of medical emergency education in dental schools. PMID- 8501302 TI - Preliminary experience with a social work rotation for advanced general dentistry students. PMID- 8501303 TI - The development of a dental student research program. PMID- 8501304 TI - Curriculum guidelines for dental anatomy and occlusion for dental hygiene. Section on Dental Hygiene Education of the American Association of Dental Schools. PMID- 8501305 TI - Curriculum guidelines for dental anatomy. Section on Dental Anatomy and Occlusion of the American Association of Dental Schools. PMID- 8501306 TI - Curriculum guidelines for occlusion. Section on Dental Anatomy and Occlusion of the American Association of Dental Schools. PMID- 8501307 TI - Biotechnologists: their marriages and future. PMID- 8501308 TI - Atherosclerosis--myths, realities and speculations. PMID- 8501309 TI - Value of venous pressure and phlebography in detecting deep vein thrombosis after major surgery and in primary venous disease. AB - A total of 60 patients from high risk group for deep vein thrombosis, which included the patients after major surgery and patients of primary venous diseases, were studied. Peripheral venous pressure measurement performed on 42 cases, detected deep vein abnormality in 6 patients (14.3%) only out of which 2 patients were designated as cases of deep vein thrombosis and 4 of chronic venous stasis syndrome. But phlebography detected deep vein thrombosis in 28 cases (46.6%) and other deep vein abnormalities in rest of the cases. PMID- 8501310 TI - Malignant lymphoma--a 15-year study report. AB - Analysis of incidence of different types of malignancies during 15 years showed occurrence of malignant lymphoma in 192 cases (4.1%). There were 82 cases (42.7%) of non-Hodgkin's lymphoma and 110 cases (57.3%) of Hodgkin's disease. Lymphocytic lymphoma, the major type observed among the non-Hodgkin's lymphoma with 58 cases (30.21%), showed a preponderance of well differentiated type (40 cases). Other cases in this group comprised mixed cellularity (2.08%), histiocytic (3.64%) and unclassified one (6.77%). Analysis of the Hodgkin's disease cases showed majority in it belonged to the mixed cellularity type (44.5%) followed by the lymphocytic predominant type (27.3%), lymphocytic depletion type (18.2%) and nodular sclerosing type (10%). The incidence of 14 cases of extranodal lymphomas was 7.3% among the lymphomas with maximum occurrence in the gastrointestinal tract (42.8%). PMID- 8501311 TI - Long-term outcome following head injury. AB - In a perspective study of follow-up of 141 head-injured patients, neurological, behavioural, neuropsychological and psychosocial parameters of outcome were used to measure the patient's functional status for 18 months. Neurophysical sequelae including seizure disorders were seen in 29 patients. Cortical functional disturbances observed were nominal difficulties in 5 patients, perseveration in 5 patients, disturbed kinetic melodies in 9 patients, frontal acalculia in 4 patients, constructional apraxia in one patient and left side neglect in one patient. These deficits were reversed except in 13 cases. Only 32 patients (22.7%) did not suffer from any behavioural changes. The role of compensation as an aetiologic factor was found in 5 patients. Out of 94 patients in whom scores in memory test was done, 11 patients performed better than their age and education-related norms. Scores in Raven's matrices for level of intellectual performance were done in 71 patients. The score was below 25th percentile in majority (58 cases). Among 130 patients with some jobs, 56 patients (43%) were fully restored. Out of 105 married patients, 45 patients (43%) had disturbed relations after head injury. Seven patients had separation of marriage. Compared to neurological deficits, behavioural and neuropsychological impairments were more prevalent and disabling. Psychosocial outcome, particularly vocational restoration was adversely affected by behavioural changes and cognitive deficits. Need for a multidisciplinary intervention to minimise the avoidable morbidity is emphasised. PMID- 8501312 TI - Unconventional use of oxytocin. AB - Various agents are in wide clinical use for the purpose of inducing and or accelerating labour. Undoubtedly, the most widely used is oxytocin. The present study represents the experience in the use of oxytocin in unconventional obstetric cases. The study comprises 300 cases where oxytocin drip was used for the initiation of labour, acceleration of labour and to control postpartum haemorrhage in both unconventional and conventional cases. The results are analysed and compared in both the groups along with the complications. Oxytocin has proved to be so safe, that there is only one contra-indication to its use and that is a grossly contracted pelvis. PMID- 8501313 TI - Shy-Drager syndrome. PMID- 8501314 TI - Sarcoma botryoides of the vagina. PMID- 8501315 TI - AIDS: perspective and strategy. PMID- 8501316 TI - AIDS and blood transfusion. PMID- 8501317 TI - Postherpetic neuralgia and its managements. PMID- 8501318 TI - Variation in course of hepatitis E in experimentally infected cynomolgus monkeys. AB - Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan. Although all 5 monkeys displayed liver enzyme elevations, viremia, virus secretion in feces, and seroconversion, two different patterns of these parameters were observed. For 4 monkeys, increased alanine aminotransferase (ALT) activity was first observed on days 21-26, viremia occurred before and during enzyme elevation, and the animals seroconverted coincidentally with the end of viremia or shortly thereafter. One of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys. The fifth monkey developed biphasic hepatitis with peaks of ALT activity on days 26 and 54. In this case, viremia and seroconversion were correlated only with the second peak of enzyme elevation and liver histopathology only with the first peak. Viral shedding in this fifth animal lasted two times longer than in other animals. PMID- 8501319 TI - Adenovirus type 8 epidemic keratoconjunctivitis in an eye clinic: risk factors and control. AB - Epidemic keratoconjunctivitis (EKC) due to adenovirus type 8 affected 126 (7%) of 1870 ophthalmology clinic patients during an outbreak. Risk factors and mode of transmission were studied by comparing cases (n = 58) and controls (n = 200) for exposure to risk factors. Pneumotonometry (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.0-27.7), multiple clinic visits (OR, 5.9; 95% CI, 3.3-10.6), and contact with an infected physician (OR, 3.3; 95% CI, 1.2-9.0) were significant risk factors for infection. The hands of 3 patients and 3 physicians with EKC were cultured before and after hand washing to assess adenovirus removal; 3 had hand cultures positive for adenovirus after hand washing. In conclusion, this outbreak appeared to be due to inadequate disinfection of instruments, especially pneumotonometers, and finger-to-eye transmission by health care workers. Hand washing did not reliably remove adenovirus from contaminated fingers. Gloving for exam of eyes with EKC may help prevent transmission. Ophthalmologists with EKC were a significant risk factor for patients and should be furloughed for the duration of communicability. PMID- 8501320 TI - Cross-reacting serum opsonins to meningococci after vaccination. AB - The opsonic activity of sera from healthy volunteers immunized with an outer membrane vesicle vaccine prepared from a Neisseria meningitidis (class 3, 44/76, B:15:P1.7,16), characteristic of the present Norwegian epidemic, has been examined. A marked increase in the phagocytosis of class 3 and nontypeable strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of postvaccination sera. Sera from vaccinees also caused a significant increase in leukocyte oxidative metabolism as measured by luminol enhanced chemoluminescence during phagocytosis of class 3 and nontypeable meningococci. An increase in serum opsonins cross-reacting with class 2 (type 2a) meningococci of different serogroups was not observed, suggesting that future meningococcal outer membrane vesicle vaccine preparations should contain both class 2 and class 3 porins in geographic areas where both class 2 and class 3 strains cause disease. PMID- 8501321 TI - Antigenic and epidemiologic properties of the ET-37 complex of Neisseria meningitidis. AB - A special collection of 336 Neisseria meningitidis strains was established that spanned the genetic variability, as defined by multilocus enzyme electrophoresis, of the ET-37 complex (228 strains isolated in different continents between the 1960s and the 1980s) and of other serogroup C meningococci (108 strains). Of the strains in the ET-37 complex, 90% were serogroup C and 10% were serogroup B. Most ET-37 complex strains were serotype 2a and serosubtype P1.5,2 or P1.5,y; most expressed class IIb pilin. Twenty-six Opa proteins differing in electrophoretic mobility or reactivity with monoclonal antibodies were variably expressed by different members of the ET-37 complex, although only four opa genes were detected in individual strains. Despite this overall diversity, most isolates from any one outbreak were fairly homogeneous. PMID- 8501322 TI - An outbreak of cholera in Maryland associated with imported commercial frozen fresh coconut milk. AB - In August 1991, the first outbreak of cholera associated with an imported commercial food product occurred among persons attending a private picnic. An epidemiologic investigation showed infection with toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, in 4 of 6 persons who had consumed coconut milk imported from Thailand. In addition, the US Food and Drug Administration recovered toxigenic V. cholerae O1, biotype El Tor, serotype Ogawa, from 1 of 6 unopened bags of the same brand (but different shipment) of coconut milk as that consumed by infected persons. Investigation in Thailand of the manufacturing process of the implicated coconut milk showed several sanitary violations, suggesting that contamination had occurred during production. This outbreak suggests a model of entrance of V. cholerae into a population and shows the need to evaluate current methods of maintaining the safety of imported foods in the United States. PMID- 8501324 TI - Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes. AB - The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)-mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD14 of monocytes, rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNF alpha) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNF alpha release, but this inhibition vanished with delaying the time of addition of rBPI23. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS. PMID- 8501323 TI - Effect of antibiotic class and concentration on the release of lipopolysaccharide from Escherichia coli. AB - The ability of six antibiotics from different classes to release radiolabeled lipopolysaccharide (LPS) from a phenotypically smooth galE mutant of Escherichia coli O111:B4 was examined. Antibiotic concentrations were 0.0625-512 micrograms/mL. LPS release increased as a function of the antibiotic concentration, reaching a limit at or near the concentration that killed the majority of bacteria. The maximum amount of LPS released by polymyxin B was 40.6% +/- 0.9%, by gentamicin 58.2% +/- 2.5%, by ciprofloxacin 65.8% +/- 2.5%, by ceftazidime 73.1% +/- 0.9%, by tetracycline 75.3% +/- 10.0%, and by imipenem 79.7% +/- 2.3%. In timed experiments, ceftazidime released 61.9% +/- 1.2%, imipenem 51.1% +/- 8.8%, and tetracycline 39.7% +/- 4.4% of the LPS within the first hour of incubation, whereas polymyxin B released 13.5% +/- 1.9%, gentamicin 9.8% +/- 3.6%, and ciprofloxacin 12.7% +/- 2.6% of the LPS (P < .05). Fluoro radiography and immunoblot analyses revealed similar migration patterns for antibiotic-released and cell-bound LPS on SDS-PAGE gels, suggesting similar O polysaccharide content in the two LPS fractions. The amount and rate of LPS release from an E. coli strain was dependent upon antibiotic class and concentration. PMID- 8501325 TI - Listeria monocytogenes-induced interferon-gamma primes the host for production of tumor necrosis factor and interferon-alpha/beta. AB - Mice acquired an enhanced capacity for the production of tumor necrosis factor (TNF) and the interferons (IFN)-alpha, and -beta shortly after intravenous injection of viable Listeria monocytogenes. By the end of the first day of a sublethal infection, mice were primed to produce 100-1000 times more endotoxin induced serum TNF than is produced by normal mice. Acquisition of the augmented capacity for TNF production was due to L. monocytogenes-induced IFN-gamma. IFN gamma also primed infected mice for IFN-alpha/beta production. However, in addition to IFN-gamma, other L. monocytogenes-induced mechanisms endowed the host with an enhanced potential for the production of IFN-alpha/beta. Antibody mediated depletion of various cell types in vivo revealed that CD8+ cells and NK cells are required for the production of L. monocytogenes-induced IFN-gamma during the first day of listeriosis. PMID- 8501326 TI - Cross-reactivity between Borrelia burgdorferi flagellin and a human axonal 64,000 molecular weight protein. AB - The serum of patients with Lyme neurologic disease contain antibodies that bind to human axonal antigens that cross-react with Borrelia burgdorferi. The sera also bind to SK-N-SH neuroblastoma cells, especially the neuritic processes of these cells. H9724, a murine IgG monoclonal antibody to B. burgdorferi flagellin, binds to an SK-N-SH cell protein of approximately 64,000 apparent molecular weight (M(r)). H9724 immunoprecipitates a protein of the same M(r) (p64) from the cells and from a delipidated preparation of human peripheral nerve. The Lyme disease patient sera that bind to human axons and SK-N-SH cells also bind to the immunoprecipitated p64. Immunologic cross-reactivity between borrelial and human axonal proteins may be involved in the immunopathogenesis of Lyme neurologic disease. PMID- 8501327 TI - Cell-mediated immune response to the recombinant 57-kDa heat-shock protein of Chlamydia trachomatis in women with salpingitis. AB - Peripheral blood mononuclear cells (PBMC) from 9 of 18 women with laparoscopy verified salpingitis proliferated in response to recombinant Chlamydia trachomatis 57-kDa heat shock protein (hsp). In contrast, PBMC from 0 of 10 women with cervicitis, 1 of 5 women with recurrent abortions, and 3 (7.1%) of 42 healthy reproductive-age women were responsive to hsp (P < .001). After passage of the hsp through an endotoxin-removing column, PBMC from 6 of 14 additional women with salpingitis were responsive to hsp, while those from 10 controls, including the 3 previously positive women, were negative. PBMC from all patients responsive to the chlamydial hsp were unresponsive to Mycobacterium bovis 65-kDa hsp. PBMC from 6 of the 15 women with a positive hsp-induced lymphocyte response were unresponsive to C. trachomatis elementary bodies. Induction of a cell mediated immune response to the chlamydial 57-kDa hsp is a common feature of an upper genital tract infection but does not appear to be limited to women with apparent chlamydial infections. PMID- 8501328 TI - Genetic diversity among strains of Mycobacterium avium causing monoclonal and polyclonal bacteremia in patients with AIDS. AB - To define the genetic diversity among Mycobacterium avium isolates from human immunodeficiency virus-infected patients, specimens were cultured prospectively, and isolates obtained from 14 patients (4 with positive blood, stool, and sputum; 6 with positive blood and stool; 3 with positive blood only; and 1 with positive stool only) were studied. Both serotyping and ribotyping had limited ability to discriminate among isolates from different patients, whereas the distinctive restriction fragment profiles resolved by pulsed-field gel electrophoresis indicated that each patient was infected by a unique strain. Of the 13 bacteremic patients, 2 were bacteremic concurrently with 2 distinct strains. The fact that M. avium isolates from AIDS patients exhibit considerable genetic diversity supports the hypothesis that the infection is acquired from various environmental sources. Further, individual patients are not infrequently bacteremic with > 1 strain simultaneously, which may need to be considered in protocols for the diagnosis and management of M. avium disease. PMID- 8501329 TI - Endemic giardiasis in New Hampshire: a case-control study of environmental risks. AB - Giardiasis is the most frequently reported diarrheal disease in northern New England. A case-control study of endemic giardiasis and environmental risk factors among residents of New Hampshire involved 273 cases from the state's 1984 disease registry and 375 controls. Giardiasis was associated with a shallow dug well as a residential water source (odds ratio [OR] = 2.4; 95% confidence interval [CI], 1.3-47.0), a recent history of drinking untreated surface water (OR = 3.4; CI, 2.1-5.5), a history of swimming in a lake or pond (OR = 4.6; CI, 2.4-86.0) or swimming in any natural body of fresh water (OR = 4.0; CI, 2.3 70.0), contact with a person thought to have giardiasis (OR = 2.3; CI, 1.4-36.0), and recent contact with a child in day care (OR = 1.5; CI, 1.0-2.1). Multivariate modeling supported these associations. Shallow wells, relatively common in New Hampshire, have not previously been established as important sources of giardiasis. PMID- 8501330 TI - Kinetics of serum and cellular interleukin-5 in posttreatment eosinophilia of patients with lymphatic filariasis. AB - Peripheral blood eosinophil counts and serum levels and in vitro production of eosinophilopoietic cytokines were assessed before and at frequent intervals after diethylcarbamazine treatment of Bancroftian filariasis. Eosinophil counts peaked at day 7 after the start of treatment (359% +/- 118% of pretreatment levels) and declined to pretreatment levels by day 17. Serum interleukin (IL)-5, undetectable in 14 of 15 patients before treatment, rose sharply but transiently, with peak levels (32 +/- 7 pg/mL) 2 days after diethylcarbamazine treatment. Granulocyte macrophage colony-stimulating factor and IL-3 were not detectable in serum at any time. In vitro mitogen-induced IL-5 levels decreased significantly in 7 of 9 patients 3 days after treatment when serum IL-5 was at near-peak levels. By day 10 IL-5 values increased in 8 of 9 patients compared with treatment values (P < .02). These data define the temporal relation between serum IL-5 levels and the subsequent development of eosinophilia and suggest that lymphocytes are the source of IL-5. PMID- 8501331 TI - Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inoculum effect. AB - Mechanisms to explain the "inoculum effect" have not been elucidated in gram positive infections. A mouse model of group A streptococcal myositis was used to compare the efficacies of two beta-lactams, penicillin and ceftriaxone, and a protein synthesis inhibitor, clindamycin, at three different inoculum sizes. beta lactams were more susceptible to inoculum effects than was clindamycin both in vivo and in vitro (P < .05). The large inocula were hypothesized to reach stationary phase of growth sooner than smaller inocula both in vitro and in vivo. The penicillin-binding protein (PBP) patterns from membrane proteins isolated from mid-log-phase and stationary-phase cultures of Streptococcus pyogenes were compared. Binding of radiolabeled penicillin by all PBPs was decreased in stationary cells; however, PBPs 1 and 4 were undetectable at 36 h. Thus, the loss of certain PBPs during stationary-phase growth in vitro may be responsible for the inoculum effect observed in vivo and may account for the failure of penicillin in both experimental and human cases of severe streptococcal infection. PMID- 8501332 TI - Molecular investigation of human immunodeficiency virus (HIV) infection in a patient of an HIV-infected surgeon. AB - Recall of patients who had been treated by a human immunodeficiency virus (HIV) infected surgeon uncovered 1 previously unknown HIV-seropositive person. Nucleotide sequencing of the gag gene and maximum likelihood phylogenetic analysis were used to investigate the relationships among sequences from the surgeon, the patient, and an anonymous blood donor from whom the patient had received blood products. The likelihoods of all possible pathways of transmission linking these persons were estimated. On these data, transmission from the surgeon to the patient was significantly less likely than from the blood donor to the patient. It is concluded that none of the recalled patients were infected by the surgeon. PMID- 8501333 TI - Human immunodeficiency virus infection among high-risk seronegative prostitutes in Nairobi. AB - To determine the frequency and duration of antibody-negative human immunodeficiency virus (HIV) infection among heterosexually exposed African women, 56 HIV-seronegative female prostitutes in Nairobi were studied. Polymerase chain reaction (PCR) was used to detect HIV DNA in peripheral blood at enrollment, and women were followed prospectively with serologic testing to determine HIV seroincidence. Six women (11%) were infected with HIV by PCR criteria at enrollment. Seroconversion occurred in 5 of these subjects within 1 12 months, while the sixth remained seronegative when last evaluated at 5 months. The cumulative annual seroconversion rate in the entire cohort was 38%. Using maximum likelihood analysis, the mean interval between HIV infection and seroconversion was estimated to be between 3 and 4 months, similar to that described for homosexual men and blood product recipients in the United States. Prolonged HIV infection in the absence of antibodies appears to be uncommon in this setting. PMID- 8501334 TI - Immunogenicity of high-titer Edmonston-Zagreb measles vaccine in human immunodeficiency virus-infected children in Kinshasa, Zaire. AB - The response to Edmonston-Zagreb vaccine (titer, 5.4 log10 pfu) was evaluated among children in a study of perinatal transmission of human immunodeficiency virus (HIV) in Kinshasa. Acute postvaccination adverse events were monitored for 49 HIV-infected and 376 non-HIV-infected infants, and measles antibody responses were assessed by ELISA for 34 HIV-infected and 255 non-HIV-infected infants. There was no increase in the incidence of common symptoms 7-10 days after vaccination. HIV-infected infants were more likely to have detectable prevaccination measles antibody, and seroconversion after vaccination was somewhat lower in HIV-infected (76.5%) than non-HIV-infected infants (85.5%). Seroconversion rates did not differ among children with or without rhinitis or fever at vaccination. High-titer Edmonston-Zagreb vaccine given at 6 months of age has the potential to provide earlier protection against measles; however, this vaccine is no longer recommended for routine use, and two doses of standard titer vaccines remains the preferred option for measles vaccination of HIV infected infants. PMID- 8501335 TI - Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS. AB - The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20 90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single agent therapy for AIDS-associated toxoplasmosis. PMID- 8501336 TI - Safety and immunogenicity of the oral, whole cell/recombinant B subunit cholera vaccine in North American volunteers. AB - A newly formulated, oral, inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was evaluated in US military personnel. In the first study, 74 subjects were given two doses 14 days apart. In the second study, 186 subjects were randomized into four groups; two groups received vaccine with either full (4 g) or half (2 g) strength bicarbonate buffer, and two groups received either full or half strength buffer without vaccine. Mild gastrointestinal symptoms were associated with full buffer (P = .02) but not with the vaccine. In the first study, 36% of all subjects and 55% with low prevaccination titers (< 1:40) had a > or = 2-fold rise in vibriocidal antibody level; > 80% of subjects developed a 4-fold rise in anti-cholera toxin (CT) titers. Post-vaccination IgA and IgG anti-CT titers were approximately 1.5-fold higher among persons receiving full strength buffer (P = .05). The WC/rBS vaccine is safe and immunogenic in North Americans, although some mild gastrointestinal symptoms occur with the high concentration of buffer necessary to protect the B subunit from gastric acid denaturation. Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response. PMID- 8501337 TI - Relationship between humoral immune responses and oral temperature during human shigellosis. AB - The relationship between oral temperature and serum IgA and IgG antibody responses to Shigella sonnei infection was examined in 65 experimentally infected adult volunteers. Although the IgA antibody response appeared to correlate directly with the rise in oral temperature following infection, stepwise regression analysis revealed other associated signs and symptoms as the critical elements underlying this apparent correlation. There was no evidence of a positive correlation between the IgG antibody response and the peak increment in oral temperature after infection. Although published data obtained in vitro suggest that fever might have a potentiating effect on antibody production, no such effect was seen in human volunteers with acute shigellosis. PMID- 8501338 TI - A large outbreak of gastroenteritis caused by diarrheal toxin-producing Bacillus cereus. AB - An outbreak of diarrhea occurred after a university field day. Of 643 attendees who returned mailed questionnaires, 139 (22%) reported illness. Persons who ate barbecued pork, which was unrefrigerated for 18 h after cooking, were five times more likely to become ill than those who did not eat pork (26% vs. 5%; relative risk, 5.4; 95% confidence interval, 1.4-20.9). A leftover pork sample grew a Bacillus cereus isolate, > 10(5) cfu/g, that produced diarrheal toxin. Thirty four percent of ill persons noted onset of illness outside the 6- to 24-h incubation period traditionally ascribed to B. cereus-mediated diarrhea, and an unusually high percentage (23%) noted fever. B. cereus may cause a wider spectrum of disease than previously described. PMID- 8501339 TI - Involvement of interferon-gamma and tumor necrosis factor-alpha in host defense against Rhodococcus equi. AB - Rhodococcus equi is a facultative, intracellular, gram-positive coccobacillus increasingly reported as an opportunistic pathogen in AIDS patients. In vitro, splenic cells of noninfected euthymic mice produced tumor necrosis factor-alpha (TNF alpha) in greater amounts when incubated with live R. equi rather than with killed bacteria. In vivo, interferon-gamma (IFN-gamma) and TNF alpha serum levels of infected euthymic mice remained below the level of detectability. Treatment of infected nude mice, which developed chronic infection, with discontinuous injections of IFN-gamma, TNF alpha, or both did not decrease bacterial colony forming units in liver, spleen, or lungs. However, treatment of infected euthymic mice, which cured a R. equi inoculum within 3 weeks, with anti-IFN-gamma or anti TNF alpha antibodies (or both) significantly increased tissue colony counts. These data argue that, in this murine model, endogenous IFN-gamma and TNF alpha are involved in the cell-mediated immunologic response against R. equi infection. PMID- 8501340 TI - Clofazimine as prophylaxis for disseminated Mycobacterium avium complex infection in AIDS. AB - A randomized, prospective, open-label, treatment versus no treatment community based clinical trial was conducted to evaluate the safety and efficacy of clofazimine as prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with human immunodeficiency virus (HIV) disease. Subjects were 110 patients with a first episode of Pneumocystis carinii pneumonia 2-4 months before enrollment or CD4 lymphocyte counts < or = 100/mm3; they were randomized to receive 50 mg of clofazimine daily or no treatment. Seven patients randomized to clofazimine developed disseminated MAC infection, compared with 6 patients receiving no treatment. Seventeen patients died: 9 in the treatment group and 8 receiving no treatment. Clofazimine at a dose of 50 mg/day is well tolerated by patients with HIV disease. Reduction in CD4 lymphocyte count to < 50/mm3 is a significant predictor of the development of disseminated MAC infection. PMID- 8501341 TI - Interleukin-8 release in baboon septicemia is partially dependent on tumor necrosis factor. AB - The role of tumor necrosis factor (TNF) in interleukin (IL)-8 release in septicemia in the baboon (2-h infusion of live Escherichia coli, 5 x 10(8) cfu/kg) was investigated. Four experiments were done: one control (n = 7) and three with pretreatment to reduce TNF plasma levels. Pretreatment was with anti TNF antibody (anti-TNF) 15 mg/kg, which neutralized circulating TNF (n = 4); 0.5 mg/kg of anti-TNF, which reduced peak TNF from 6.2 ng/mL (controls) to 0.6 ng/mL (n = 4); and a xanthine derivate (HWA138), which reduced TNF to 1 ng/mL (n = 5). With TNF levels < 1 ng/mL, a significant reduction of circulating IL-8 from 10.4 ng/mL (peak) in controls to 1 ng/mL (peak) in anti-TNF-treated animals was found, but with HWA138 only some decrease in IL-8 was seen. Despite high endotoxin levels (10-30 ng/mL peak), neutralization of TNF resulted in diminished release of IL-8 and significantly lower levels of granulocyte elastase. PMID- 8501342 TI - Interferon-gamma protects endothelial cells from damage by Candida albicans. AB - Endothelial cells activated with interferon-gamma (IFN-gamma) have been shown to inhibit the replication of Toxoplasma gondii. To determine if this cytokine protects endothelial cells from damage by Candida albicans, human umbilical vein endothelial cells were pretreated with IFN-gamma and infected with C. albicans; endothelial cell damage was measured by the release of 51Cr. Pretreatment with IFN-gamma decreased the extent of endothelial cell injury caused by C. albicans by up to 100% +/- 8.2%. This diminution of endothelial cell damage was confirmed by scanning electron microscopy. The degree of protection was dependent on the concentration of IFN-gamma, with maximum protection occurring at 13 units/mL. Higher concentrations of IFN-gamma were toxic to the endothelial cells. Pretreating the endothelial cells with this cytokine had no effect on candidal germination and growth, suggesting that IFN-gamma stimulates endothelial cells to become resistant to or inhibit the action of candidal virulence factors. PMID- 8501343 TI - An improved method for the prolonged maintenance of Pneumocystis carinii in vitro. AB - A culture system for rat-derived Pneumocystis carinii was developed that allows the long-term maintenance of viable organisms in vitro. Organisms were derived from the lungs of immunosuppressed rats infected with P. carinii. P. carinii was maintained in culture with human embryonal lung (HEL) fibroblasts and Eagle MEM for up to 42 days. Passage of organisms was done by reinoculation of infected HEL cells with attached P. carinii onto a fresh monolayer of confluent cells. Rats pretreated with trimethoprim-sulfamethoxazole and inoculated with cultured organisms (up to day 42) developed P. carinii pneumonia by 6 weeks while control animals remained uninfected. P. carinii was able to be harvested from these lungs and reintroduced into tissue culture. Cultures have been maintained for up to 6 weeks without a substantial loss of P. carinii viability. In combination with intratracheal inoculation, this system raises the possibility of maintaining stable laboratory strains of P. carinii. PMID- 8501344 TI - Ancylostoma factor Xa inhibitor: partial purification and its identification as a major hookworm-derived anticoagulant in vitro. AB - Soluble protein extracts from adult Ancylostoma hookworms were found to contain an anticoagulant activity that markedly prolonged both the prothrombin time (PT) and partial thromboplastin time (PTT). By chromogenic peptide substrate and clotting time assays, the anticoagulant activity was attributed to a specific inhibitor of clotting factor Xa. The hookworm anticoagulant was partially purified by ion-exchange column chromatography. Those column fractions containing anti-Xa activity by chromogenic assay also prolonged the PT and PTT as well as the factor X (Stypven) clotting time. These data suggest that this potent factor Xa inhibitor is a major anticoagulant from the adult Ancylostoma hookworm. PMID- 8501345 TI - Interaction of lectins with Cryptosporidium parvum. AB - Cell surface carbohydrates from four clinical isolates of Cryptosporidium parvum were analyzed by agglutination assays using a battery of 20 highly purified lectins with affinity for receptor molecules containing N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine, galactose, mannose, glucose, fucose, and N acetyl-neuraminic acid. Tomentine, a lectin from the green seaweed Codium tomentosum, and UEA-II lectin, from Ulex europeus, both of them GlcNAc-specific lectins, agglutinated the oocysts. Subsequent inhibition assay confirmed the presence of this sugar on the surface of Cryptosporidium parvum oocysts. Codium fragile lectin, from another green seaweed, also exhibited agglutination activity against the oocysts. This is the first published demonstration of such an interaction between a human coccidian and lectins from seaweeds. PMID- 8501346 TI - T cell response to Mycobacterium tuberculosis. AB - The T cell-mediated acquired immune response to infection with Mycobacterium tuberculosis, both in humans and in experimental models in the mouse, is a complex event believed to involve a variety of T cell subsets that manifest themselves in numerous functions, including protection, delayed-type hypersensitivity, cytolysis, and the establishment of a state of memory immunity. These functions in turn involve the secretion of an array of cytokines, several of which direct cells of the monocyte/macrophage axis to contain and destroy the invading bacilli. This article reviews the development of these ideas, both from clinical experience and from basic research in animal models. In addition, the newly emerging hypothesis that the secreted or export proteins of M. tuberculosis are the key protective antigens leading to the initial expression of acquired specific resistance to this organism is examined. PMID- 8501347 TI - Use of the human immunodeficiency virus virion as a universal standard for viral RNA quantitation by reverse transcription-linked polymerase chain reaction. PMID- 8501348 TI - Quaternary amine (protamine sulfate) is bactericidal to Staphylococcus epidermidis. PMID- 8501349 TI - Salicylic acid decreases extracellular biofilm production by Staphylococcus epidermidis: electron microscopic analysis. PMID- 8501350 TI - EIA for detection of Rochalimaea henselae-reactive IgG, IgM, and IgA antibodies in patients with suspected cat-scratch disease. PMID- 8501351 TI - Free fatty acids in serum of patients with acute necrotizing or edematous pancreatitis. AB - Serum concentrations of free fatty acids (FFA) were assayed in 20 patients with acute necrotizing pancreatitis (ANP). Pancreatic and peripancreatic fat necrosis was verified on operation and/or by contrast-enhanced computed tomography. For comparison, 20 patients with acute edematous pancreatitis (AEP) were examined. On admission, FFA serum levels were 1.14 +/- 0.12 (SEM) mmol/L in ANP and, thus, significantly (p < 0.03) higher than in AEP (0.78 +/- 0.09 mmol/L). The two groups also differed in the later course: in ANP, the FFA values remained raised (d 5-11:0.86 +/- 0.13 mmol/L; p > 0.05 vs day 1), whereas in AEP, the FFA concentrations normalized within 1 wk (d 2-4:0.52 +/- 0.11 mmol/L; d 5-11:0.39 +/ 0.05 mmol/L; p < 0.05 vs day 1 and p < 0.01 vs ANP). Serum FFA correlated positively with C-reactive protein levels (rs = 0.42; p < 0.01), but has less discriminating potency between ANP and AEP. In AEP, the initial peak may correspond to the disease outburst itself and to unspecific stress. In ANP, the higher and sustained elevation of FFA may predominantly mirror the ongoing pancreatic parenchymal and extrapancreatic fat necrosis, and be pathophysiologically relevant, especially in view of significantly reduced serum albumin levels in ANP. PMID- 8501352 TI - Rat pancreatic phospholipase A2. Purification, localization, and development of an enzyme immunoassay. AB - Phospholipase A2 (PLA2, E.C. 3.1.1.4) was purified from rat pancreatic tissue by heat treatment of the homogenate and use of cation-exchange chromatography on a CM-Sepharose column. The enzyme was apparently homogenous on SDS polyacrylamide gel electrophoresis, and its mol wt was estimated to be 14,400. An antiserum raised against rat pancreatic PLA2 in a rabbit was used in a solid-phase enzyme immunoassay employing inorganic pyrophosphatase (E.C. 3.6.1.1) as the enzyme label. As measured by this assay, the concentration of pancreatic PLA2 in plasma was found to be above normal in rats with hemorrhagic pancreatitis induced by an intraductal injection of sodium taurocholate. PLA2 was localized in pancreatic acinar cells and in the chief cells in the mucosa of the glandular stomach by immunohistochemistry. By immunoelectron microscopy, the immunogold conjugates were mainly located on profiles of zymogen granules in acinar cells. PMID- 8501353 TI - Heterotopic autotransplantation of a pancreas segment with enteric drainage after total or subtotal pancreatectomy for chronic pancreatitis. AB - Four patients with chronic alcoholic pancreatitis and one patient with idiopathic chronic pancreatitis, who had total or subtotal distal pancreatectomies for persistent pain, underwent simultaneous autotransplantation of a pancreas segment to preserve the pancreatic function. The segment was autotransplanted heterotopically to the iliac fossa with anastomosis of the splenic vessels to the iliac vessels to prevent reinnervation, and the pancreatic duct was anastomosed to the intestine to preserve exocrine function. Postoperatively, the patency of the graft vessels was confirmed by angiography in every patient. Complete pain relief has been obtained in all patients with a followup duration of 4-89 mo. Except for one patient who had been treated preoperatively with insulin injections for diabetes, the patients remained normoglycemic without exogenous insulin administration and demonstrated satisfactory insulin secretion during a 75-g oral glucose tolerance test. An exocrine pancreatic diagnostant test using p aminobenzoic acid yielded nearly similar levels to the preoperative value for all patients. Heterotopic autotransplantation of the pancreas segment appears to be effective for preserving pancreatic function, as well as providing permanent pain relief for patients with chronic pancreatitis who require extensive resection of the pancreas. PMID- 8501354 TI - Duration and potency of anticholecystokinin action of subcutaneous and oral loxiglumide on cerulein-stimulated pancreatic exocrine secretion. AB - The duration and the potency of the antiCCK activities of loxiglumide given by sc and oral routes were examined in rats. Pancreatic juice flow and protein output in response to an iv bolus injection of cerulein (100 ng/kg body wt) were measured at specified time intervals from 1-12 h after loxiglumide administration. Subcutaneous loxiglumide (10 g/kg body wt) effectively suppressed cerulein-stimulated protein output for 4 h and pancreatic juice volume for 6 h, when total outputs during a 60-min period after cerulein stimulation were compared with the control value without loxiglumide pretreatment. Oral dose of loxiglumide exerted longer-term anti-CCK activity (protein output: 6 h, pancreatic juice: 8 h) than the same sc dose. In addition, oral loxiglumide showed more potent suppression of protein output than the same sc dose at the corresponding time interval. Higher oral dose of loxiglumide (50 mg/kg body wt) caused longer inhibition on both protein (8 h) and pancreatic juice secretion (12 h). These results suggest that the half-life of loxiglumide given by oral route is longer than that by sc route or that the bioavailability of oral loxiglumide is higher than that of sc dose. The present study demonstrates that loxiglumide, given either by sc or by oral route, has long duration of action in antagonizing responses to exogenously administered cerulein. PMID- 8501356 TI - Serum pancreatic stone protein in pancreatic diseases. AB - Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean +/- SD = 1075.4 +/- 2849.1 ng/mL, n = 33) was significantly higher than that in controls (78.6 +/- 31.8 ng/mL, n = 37, p < 0.01), chronic pancreatitis (156.8 +/- 82.8 ng/mL, n = 32, p < 0.05), and pancreatic cancer (148.468.8 ng/mL, n = 26, p < 0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0 +/- 1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r = 0.22, p < 0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflex from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis. PMID- 8501357 TI - Lengthening in the upper limb. PMID- 8501355 TI - A specific and sensitive radioimmunoassay for rat C-peptide. AB - A sensitive and specific radioimmunoassay for rat serum C-peptide (RCP) has been developed and validated using a guinea pig anti-rat C-peptide antibody to synthetic rat C-peptide. Negligible crossreactivity (< 0.01%) to human proinsulin was observed, whereas human insulin, human pancreatic polypeptide (hPP), porcine insulin, porcine C-peptide, bovine insulin, rat insulin, porcine-PP, and glucagon, respectively, did not produce measurable displacement of RCP tracer. Human C-peptide even in a supraphysiological concentration range crossreacted poorly (< 0.1%). The sensitivity limit of the assay calculated at +/- 3 standard deviations was 24.2pM (0.07 ng/mL). RCP standard concentrations ranged from 25 1600pM. The intraassay- and between assay-coefficient of variations (CV) were 3.5 6.1% and 4.1-9.5%, respectively. The mean percentage recovery of RCP added to rat serum samples was 100.8 +/- 2%. Serum volume dilution from 25 to 100 microL did not significantly alter the expected RCP level. Migration of rat serum C-peptide and that of synthetic RCP were identical in a Sephadex G-50 chromatographic analysis. The mean fasting and postprandial plasma RCP levels in normal rats were 102 +/- 15 pM and 485 +/- 75pM, respectively. RCP levels following intravenous glucose tolerance test in diabetic and nondiabetic rats were consistent with expected patterns. In conclusion, we have developed and validated a rat C-peptide assay that is sensitive, simple, and specific for RCP in serum. The assay provides a reliable tool for studies of diabetes using rodent animal models. PMID- 8501358 TI - Resection of a periosteal osteosarcoma and reconstruction using the Ilizarov technique of segmental transport. AB - The reconstruction of a large diaphyseal bone defect is a surgical challenge. Autologous bone grafts are usually insufficient to bridge the gap and allografts are prone to infection and may pose problems with internal fixation. Another solution is presented for the reconstruction of a large ulnar defect due to tumour resection, using the Ilizarov technique of segmental transport. PMID- 8501360 TI - Thumb replantation: survival factors and re-exploration in 122 cases. AB - We analyzed 122 cases of replantation following complete amputation of the thumb and correlated various factors with rates of survival. The overall survival rate of thumb replantation was 71%. The type of amputation markedly affected survival rate. In minimally damaged amputations, the time period from injury to the start of surgery was the only significant factor related to survival. Other factors such as age, smoking history, amputation level, the number of vessels reconstructed and the method used did not relate statistically to survival. With avulsion amputations, the survival rate of replantation at and proximal to the MP joint was significantly better than replantation distal to the MP joint. 20 thumbs required re-exploration for vascular compromise; nine of these were salvaged (45%). PMID- 8501359 TI - Treatment of post-replantation retardation of bone growth by callus distraction. A report of two cases. AB - Hand and forearm replantation in children may lead to premature closure of the distal radial or ulnar growth-plates. Following successful replantation, bone growth may be retarded, resulting in a length discrepancy between the radius and ulna with secondary deviation of the replanted hand. We present two cases in which callus distraction was employed to correct a length discrepancy. The relative merits of the various treatment options are discussed. PMID- 8501361 TI - Replantation of fingertips. AB - During the period between 1976 and 1990, 207 fingertips have been replanted in 133 male and 55 female patients whose ages ranged from 14 months to 80 years, with an average of 32.7 years. Of the 207 fingers with complete amputation, 131 were injured in zone 1 and 76 in zone 2. The minimum follow-up period was 6 months. The results of zone 1 amputation have been analyzed according to the type of injury. The survival rate was 100% in clean-cut amputation, 95% in blunt-cut, 64.3% in crush and 65.5% in avulsion. From the point of view of survival and function, satisfactory results were obtained in amputations in zone 2, and in all cases in zone 1 that were clean-cut or blunt-cut. PMID- 8501362 TI - The use of the veins of the thenar eminence in digital revascularization and replantation. AB - Use of the small veins of the thenar eminence as an alternative source of vein grafts in distal digital reconstruction is presented. PMID- 8501363 TI - The limit of graft length in the experimental use of muscle grafts for nerve repair. AB - In order to investigate whether there is any length limit for the success of freeze-thawed muscle grafts when used for peripheral nerve repair, an experimental study was undertaken in the rabbit. Previous work has shown 4 cm muscle grafts in the rabbit sciatic nerve to be successful. On this basis 5 cm and 10 cm muscle grafts were inserted into the common peroneal nerve and compared with 5 cm and 10 cm free nerve grafts. Recovery was assessed after 250 days using whole nerve physiology, weights of innervated muscles, and histological examination of the nerve. At both 5 cm and 10 cm the nerve grafts performed significantly better than the muscle grafts, the 10 cm muscle grafts being totally ineffective. The implications of these results for the application of freeze-thawed muscle grafting in peripheral nerve surgery and the possible factors limiting length of grafting are discussed. PMID- 8501364 TI - The spaghetti wrist. Simultaneous laceration of the median and ulnar nerves with flexor tendons at the wrist. AB - The outcome of 15 patients who sustained simultaneous laceration of the median and ulnar nerves with flexor tendons at the wrist is described. Primary nerve repair yielded satisfactory results, the median nerve achieving a better outcome than the ulnar nerve. Most patients regained a functional range of wrist movement. Flexor tendons yielded the poorest results. A functional, albeit impaired outcome can usually be anticipated following this severe injury. PMID- 8501365 TI - Ultrasonography in the diagnosis of carpal tunnel syndrome caused by an occult ganglion. AB - A case is reported of carpal tunnel syndrome caused by an occult ganglion which was diagnosed preoperatively by ultrasonography. PMID- 8501366 TI - The use of ultrasonography in detection of synovitis in carpal tunnel syndrome. AB - The findings of pre-operative ultrasonography of the carpal tunnel were compared with synovial histology in 50 surgically treated wrists with carpal tunnel syndrome. Eight wrists with a massive hypoechoic area (group 3) had synovitis. 28 with a minimal hypoechoic area (group 1) had no evidence of inflammation. 14 with a moderately increased hypoechoic area (group 2) consisted of three with synovitis, four with lymphocytic infiltration and seven without inflammation. Group 3 strongly indicates synovitis, in which case one should consider aetiology other than the idiopathic cause. Bilateral synovial thickening suggests carpal tunnel syndrome as the initial clinical picture of rheumatoid arthritis, and group 1 indicates idiopathic carpal tunnel syndrome provided that there are no primary causes. PMID- 8501367 TI - Prediction of the outcome 24 hours after carpal tunnel decompression. AB - A prospective study has been performed on 47 wrists treated by surgical decompression for carpal tunnel syndrome. In all cases where there was symptomatic relief within the first 24 hours postoperatively, a good or excellent outcome was obtained when the patients were reviewed six weeks after surgery. If subjective improvement was not obtained by 24 hours, a good outcome was still possible but a poor outcome became more likely. PMID- 8501368 TI - An anatomical variation of the palmar cutaneous branch of the median nerve. AB - A case is presented of an anomalous course of the palmar cutaneous branch of the median nerve. Wide and meticulous exposure is necessary to avoid injury to all variations of this nerve and the use of a "safe" incision will not always avoid risk of injury. PMID- 8501370 TI - Malignant schwannoma mistakenly diagnosed as carpal tunnel syndrome. AB - A rare nerve sheath tumour masquerading as carpal tunnel syndrome is described. It arose in a digit, with perineural spread proximally along the median nerve. PMID- 8501369 TI - Haemostasis during carpal tunnel release under local anaesthesia: a controlled comparison of a tourniquet and adrenaline infiltration. AB - A randomized controlled comparison of tourniquet and local adrenaline infiltration for control of bleeding was performed in patients undergoing bilateral carpal tunnel release under local anaesthesia. Visual analogue scores for intra-operative pain were substantially greater for tourniquet (mean score 4.7) than for adrenaline (2.2). Incomplete control of bleeding was responsible for longer operating time and for the surgeons' perception of slightly greater operative difficulty with the use of adrenaline. There were no complications attributable to the use of adrenaline. The use of adrenaline-containing local anaesthesia for carpal tunnel release avoids tourniquet pain and is preferred by patients. PMID- 8501371 TI - Recurrent carpal tunnel syndrome. Clinical testing indicating incomplete section of the flexor retinaculum. AB - Based on five observations of recurrent carpal tunnel syndrome, a distally incomplete section of the flexor retinaculum can be identified on clinical grounds: the wrist flexion test becomes negative and the tourniquet test still remains positive. PMID- 8501372 TI - Fracture dislocation of the fifth metacarpal resulting in compression of the deep branch of the ulnar nerve. AB - A volar fracture dislocation of the base of the fifth metacarpal resulted in compression of the deep branch of the ulnar nerve. Operative correction of the deformity resulted in full recovery. PMID- 8501373 TI - Stabilization of multiple metacarpal fractures: a new use for the Charnley toe fusion clamp. AB - Surgery is often required to ensure adequate reduction and fixation of multiple fractures of the metacarpals. In order to stabilize metacarpal fractures with transverse Kirschner wire fixation, the authors have used a simple modification of the Charnley compression clamp designed for toe fusion. PMID- 8501374 TI - Isolated dislocation of the pisiform bone. AB - A case is reported of dislocation of the pisiform, successfully treated by conservative means. PMID- 8501375 TI - Carpometacarpal dislocation of the thumb associated with fracture of the trapezium. AB - Dislocation of the first carpometacarpal joint combined with a vertical intra articular fracture of the trapezium is a rare injury. A case is described treated by open reduction of the trapezial fracture and reconstruction of the first intermetacarpal ligament using a slip of abductor pollicis longus tendon. PMID- 8501376 TI - Reinsertion of the ruptured ulnar collateral ligament of the metacarpophalangeal joint with an absorbable self-reinforced polylactide tack. AB - 70 patients with total avulsion or rupture of the ulnar collateral ligament of the first metacarpophalangeal joint were treated surgically, using an absorbable self-reinforced poly-L-lactide mini-tack placed through the ligament and a channel in the base of the proximal phalanx. The device stabilized the joint immediately, and 69 ligaments remained stable at 6 months. The subjective result was good or satisfactory in 66 of the cases. One case needed further surgery for pain in the scar and another developed local infection 9 months post-operatively. On the basis of these findings, the new absorbable fixation method seems to be a suitable method for clinical use. PMID- 8501377 TI - Minimal tourniquet pressure to maintain arterial closure in upper limb surgery. AB - Complications of the pneumatic tourniquet used during limb surgery result from excessive direct pressure. Traditional recommendations suggests parameters for maximum pressure and time limits rather than the minimal effective pressure to achieve a bloodless field. A clinical study was undertaken to evaluate the pneumatic tourniquet setting required for adequate haemostasis in the upper limb. The correlations between several possible influencing parameters (age, sex, arm fat thickness, extremity length, systolic, diastolic, and mean blood pressures) and the minimal pneumatic tourniquet pressure at which the peripheral pulse reappeared were studied in 50 patients undergoing surgery, using a Doppler stethoscope. The average Doppler Opening Pressure was 168.5 +/- 42.7 mmHg and the only significant clinical variable was the mean blood pressure. From these results an equation was derived to predict the minimal effective tourniquet pressure. The mean calculated tourniquet pressure was 202.3 +/- 34.2 mmHg, well below the 250 to 300 mmHg previously recommended. The technique consisted of inflating the tourniquet to a pressure of 300 mmHg, then reducing it to the calculated value. A bloodless field was maintained in all patients. PMID- 8501378 TI - An algorithm for acute wrist trauma. A systematic approach to diagnosis. AB - A systematic approach to the acute traumatized wrist is of importance to achieve early diagnosis, with efficient use of advanced imaging modalities. In a 6-month period 641 patients aged 15 years or over were examined using an algorithm for acute wrist trauma in order to secure early and appropriate treatment. In 293 (46%) cases routine radiographic examination supplied sufficient information to establish a fracture diagnosis. All 33 scaphoid fractures (including five scaphoid non-unions) were demonstrated on the initial X-ray examination. In 56 patients (9%) scintigraphy proved useful for selecting cases in need of further radiographic examination. Among 31 patients with focal activity on bone scintigraphy, CT and/or tomography revealed eight distal radial fractures, one fracture of the ulnar styloid, and eight fractures of carpal bones. Fractures were revealed using tomography and/or "hot spot views" in patients with negative CT examinations suggesting that further examinations should be performed in cases with increased focal activity on bone scintigraphy and a negative CT examination. PMID- 8501379 TI - Arthroscopic diagnosis of scapho-lunate instability in the absence of X-ray abnormalities. AB - 26 patients with at least one clinical symptom that could indicate a tear of the scapho-lunate interosseous ligament but normal static and dynamic radiographs were examined by arthroscopy. We found that a diagnosis of scapho-lunate instability could be established by dynamic manoeuvres during radio-carpal and mid-carpal arthroscopy. Five patients were found to have true scapholunate instability. Six tears of the interosseous ligament without instability were also detected but it was doubtful if the tear was the origin of the painful symptomatology. This experience suggests that dynamic manoeuvres during arthroscopy are superior to other methods in diagnosing scapholunate instabilities at the pre-radiographic stage. PMID- 8501380 TI - Scaphoid non-union: factors affecting the functional outcome of open reduction and wedge grafting with Herbert screw fixation. AB - 50 patients with scaphoid non-union were treated by open reduction, anterior wedge bone grafting and internal fixation using the Herbert screw. Intra operative image intensifier control enabled us to insert the screw into the scaphoid accurately. An excellent or good functional outcome was less likely when more than 5 years had elapsed since injury, the non-union was in the proximal third, when sclerosis of the proximal fragment was present, and when reduction of carpal and scaphoid deformity was unsatisfactory. These four factors are believed to be the primary determinants affecting the functional results of the surgical treatment of scaphoid non-union, even when bony union is achieved. PMID- 8501381 TI - Articular fractures of the digits: a prospective study. AB - We report a prospective study of 92 articular fractures of the digits. The treatment protocol was based on functional stability and acceptable alignment rather than on joint congruity. 54% of patients had good results, with 22% fair and 24% poor results being recorded. These results are similar to reports of treatment of finger fractures in general and suggest that for articular fractures of the digits, stability and alignment are more important factors than joint congruity in determining short-term outcome. Compound fractures and those associated with comminution, significant soft tissue damage and marked displacement at presentation have a worse prognosis. PMID- 8501382 TI - Regeneration of the distal phalanx. A case report. AB - A patient who suffered a traumatic avulsion of the distal phalanx of the right index finger is described. Following simple wound toilet and closure, the distal phalanx generated to give an excellent functional result. PMID- 8501383 TI - Tendon transfer to restore extension of the thumb using abductor pollicis longus. AB - 20 patients with rupture or division of extensor pollicis longus (EPL) underwent tendon transfer using abductor pollicis longus (APL). All patients except one were reviewed and examined between 6 and 80 months after surgery. The subjective and objective results were satisfactory and are presented with details of the technique and its advantages and limitations. PMID- 8501384 TI - The extended palmaris longus tendon graft. AB - A technique is described of increasing the length of a palmaris longus tendon graft by including palmar aponeurosis. The additional 5 cm is often useful in treating high flexor tendon ruptures, especially at the wrist level, without the need for an additional incision. PMID- 8501385 TI - Triggering after partial tendon laceration. AB - Triggering and tendon flap formation were studied after a transverse laceration of 50% of the width of the flexor digitorum profundus tendons of the hind limb of 14 adult sheep at various intervals after injury. The tendon laceration was not repaired and there was no post-operative immobilization. Triggering was not caused by bulbous scar formation but by the bunching of the tendon fibres proximal or distal to the laceration site. This bunched part of the tendon appeared to become incorporated into the healing process, with gradual spontaneous resolution of triggering. Failure of incorporation of this bunched part resulted in the formation of a flap in two tendons. PMID- 8501387 TI - A high velocity, high temperature injection injury. AB - A case of high velocity, high temperature injection injury to the right index finger during welding is reported PMID- 8501386 TI - The natural history of adult trigger thumb. AB - 30 consecutive adult patients presenting with trigger thumb (31 thumbs) were entered prospectively into a study to determine the natural history of the condition. Five patients insisted on treatment and could not be followed to resolution, but the rest resolved spontaneously after an average duration of symptoms of 6.8 months (range 2-15). There was a small but non-functional reduction in movement of the thumb in some of the patients: six lost an average of 7 degrees of abduction and ten had an average loss of opposition of 1.4 (Kapandji grade). The remaining patients made a full recovery. PMID- 8501388 TI - Subcutaneous emphysema of the upper limb: an air-gun injury. AB - We describe a case of subcutaneous emphysema of the hand and forearm from an air gun. PMID- 8501389 TI - Prevalence of Dupuytren's contracture and its correlation with degenerative changes of the hands and feet and with criteria of general health. AB - The prevalence of Dupuytren's contracture and its coincidence with degenerative changes in the hands and feet as well as loss of distal pulses, were studied in 574 55-year-old residents of Malmo, Sweden. Dupuytren's contracture occurred in 6% of the subjects studied, predominantly in men. Dupuytren's contracture was more common in men with degenerative changes in the feet and in men with signs of impaired arterial blood flow in the lower limbs. Men with Dupuytren's contracture had significantly less subcutaneous fat tissue, as measured by a triceps skinfold index, than men without Dupuytren's contracture. Other signs of general health, occupational work load or psychosocial factors did not interact with Dupuytren's contracture in the current study. PMID- 8501390 TI - A study of the repeatability of the diagnosis of Dupuytren's contracture and its prevalence in the grampian region. AB - 200 consecutive geriatric patients over 60 years of age (100 men and 100 women) were examined for signs of Dupuytren's contracture and questioned about certain risk factors thought to be associated with the disease. Each patient was examined, independently, by two orthopaedic surgeons. The diagnosis of Dupuytren's contracture was established by the finding of a thickening in the palm fixed to the palmar fascia as a nodule or band. However each patient was also examined for skin tethering, flexion contractures of digits and knuckle pads. The results were then analysed and a Kappa test performed on the data to assess the inter-observer variability in eliciting the signs of Dupuytren's contracture. Using the Kappa test agreement between the two observers was found to be, on average, 1.0 for observing flexion contractures, 0.8 for observing skin tethering, 0.7 for observing palmar nodules and 0.7 for observing knuckle pads. The two observers both made the diagnosis of Dupuytren's contracture in 21% of women and 39% of men. These figures are high compared with previously published data from other centres and confirm the locally held belief that Dupuytren's contracture is particularly prevalent in North-east Scotland. PMID- 8501391 TI - A clinical, ultrastructural and immunochemical study of Dupuytren's disease. AB - Aponeurotic tissue from seven normal subjects and from apparently unaffected branches, nodules and cords of 16 Dupuytren's patients were compared. Control tissue was characterized by polymorphous cells, showing cytoplasmic microfilament bundles, numerous pinocytic vesicles, basement membrane-like structures, and a thick coat of interwoven filaments, and by type I- and III-positive heterogeneous collagen fibrils, fibronectin, vitronectin, decorin and proteoglycans. The clinically normal branches consisted of fibroblast-like cells, small type III highly positive collagen fibrils, fibronectin and proteoglycans. Nodules and fibrotic cords contained fibroblast-like cells, type I and III collagen, fibronectin and proteoglycans. Myofibroblast-like cells in only five out of 16 patients were present. There was no relation between clinical stage and structural alterations; the whole aponeurosis always seemed to be involved; cord retraction would seem to depend on the interactions among fibroblast-like cells and matrix components and among matrix macromolecules themselves. PMID- 8501392 TI - Revascularization of nerve grafts. PMID- 8501393 TI - Scapholunate dissociation occurring with scaphoid fracture. PMID- 8501394 TI - Separation of alveolar macrophages and dendritic cells via autofluorescence: phenotypical and functional characterization. AB - In a previous study we demonstrated that an increase of monocytes and dendritic cells (MDC) was In the current study, the bright autofluorescence of alveolar macrophages (AMs) was used to separate them efficiently from the MDC. Sorting of freshly isolated BAL cells resulted in a high-autofluorescent fraction, consisting predominantly of AMs, and a low-autofluorescent fraction containing the MDC, lymphocytes, and granulocytes. Thus, a clear separation between suppressive (AM) and stimulating (MDC) activity was obtained as shown in antigen specific T cell responses. Flow cytometric parameters, density fractionation, and a series of ED monoclonal antibodies raised against rat macrophage antigens showed that both AMs and MDC were diverse populations. After overnight culture, more than 80% of an MDC population with a density range of 1.065-1.079 changed to a lower density (< 1.056) and morphologically developed into DCs with many processes. Concomitantly, monoclonal antibody ED1 expression changed from a granular pattern to a discrete juxtanuclear spot localization. PMID- 8501395 TI - Cytokine mRNA expression in livers of mice infected with Listeria monocytogenes. AB - Temporally distinct groups of cytokine expression was observed by reverse transcription-polymerase chain reaction assay, in situ hybridization, and immunohistochemistry in the livers of Listeria monocytogenes-infected mice. One group consisted of interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha), and interleukin-10 (IL-10), for which mRNAs were induced within 1 day after challenge. A second group consisted of IL-2 and IL-4, for which mRNA was strongly expressed at 1 day but then suppressed at 3 days into the infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, and IL-6 mRNA constituted a third group, which was increased at 3 days after challenge. Distributions of cytokine mRNA-expressing cells in the liver was observed by in situ hybridization. Cells expressing TNF-alpha and IL-1 alpha mRNA were present throughout liver granulomas, whereas cells that expressed IFN-gamma mRNA were observed mostly along the periphery of granulomas. Cells expressing IL-2, IL-4, IL-6, IL-10, and GM-CSF mRNA were distributed principally in the hepatic sinuses. Cells expressing IL-10 mRNA increased in number early in the infection when L. monocytogenes was multiplying in the liver. We conclude that cytokine mRNA expression during the early phases of L. monocytogenes infection in mice is temporally regulated and that IFN-gamma, TNF-alpha, and IL-1 alpha are expressed by cells associated with hepatic granulomas. PMID- 8501396 TI - Mitogenic signal transduction in T lymphocytes in microgravity. AB - The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin 2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation. PMID- 8501397 TI - Granulocyte activation induced by intense interval running. AB - Activation of granulocytes has been associated with normal immune function, inflammation, and exercise-induced muscle damage. The effect of intense interval running on granulocyte activation was examined by use of flow cytometry, monoclonal antibodies, and spectrophotometric techniques. Eight trained males [maximal oxygen uptake VO2max, mean (SD) = 64.4 (3.6) ml/kg/min; age 30.1 (4.8) years] undertook an intense interval exercise (treadmill running) protocol to exhaustion. Subjects completed an average of 16.5 one-minute runs. Granulocyte expression of CR3 (CD11b), receptor for complement component C3bi (6 and 24 h post-test), and Fc gamma RIII (CD16) (24 h post-test) and the plasma concentration of elastase-inhibitor complex (1 h post-test) increased significantly (all P < .05). Subjects (8 of 8) exhibited a post-test decrease at either 1 or 6 h (P < .01) and a 24-h post-test significant increase (7 of 8; P < .05) in granulocyte 90 degrees light scattering (LS). Plasma lactoferrin (Lf) concentration, although increased by 17% at 6 h post-test, was not significantly different from resting values at any sampling point. Changes in plasma Lf and median channel 90 degrees LS were significantly correlated (r = -.43, P = .04), raising the possibility of monitoring exercise-induced granulocyte activation (degranulation) by flow cytometry. Intense interval exercise appears to induce granulocyte activation, as manifested by release of granule proteins and changes in 90 degrees LS and expression of both Fc and complement receptors. PMID- 8501398 TI - Monocyte urokinase expression: modulation by interleukins. AB - This study delineates the regulatory effect of interleukin-1 (IL-1) and interleukin-2 (IL-2) on monocyte plasminogen activator (PA) activity. Mononuclear phagocytes regulate net PA activity by modulating the expression of urokinase type PA (uPA) and a specific plasminogen activator inhibitor, PAI-2. To understand the regulation of mononuclear phagocyte PA activity, it is important to compare the expression of uPA and PAI-2. In this study, we determined the relative abundance of secreted PA and PA inhibitor activity in human monocyte conditioned medium after stimulation with human recombinant IL-1 or IL-2. In agreement with our previous description of tumor necrosis factor-alpha and interferon-gamma stimulation of mononuclear phagocytes, we found no detectable PA activity in conditioned medium. Both IL-1 and IL-2 had dose-dependent effects, significantly up-regulating PA inhibitor activity in monocyte-conditioned medium (up to 11-fold). To further investigate the mechanism underlying this effect, Northern blot analysis was done to measure steady-state mRNA for uPA and PAI-2. Consistent with the increase in secreted PA inhibitor activity, we found that both IL-1 and IL-2 significantly increased steady-state mRNA for PAI-2. In addition, however, both IL-1 and IL-2 increased steady-state mRNA for uPA. IL-1 appears to increase mRNA for uPA to a greater extent than does IL-2. We conclude that IL-1 and IL-2 modulate monocyte proteolytic activity by increasing expression of uPA and PAI-2 with a resultant predominance of PAI-2. We further conclude that cytokine-specific regulation of plasminogen activity is achieved partly by varying the proportionate expression of uPA and PAI-2. PMID- 8501399 TI - Mechanisms generating functionally heterogeneous macrophages: chaos revisited. AB - Macrophage populations exhibit a wide range of antigenic and functional phenotypes, including cytokine production, response to immunomodulatory stimuli, and clearance of pathogens. The expanding clinical exploitation of recombinant growth factors and cytokines with the potential to regulate the production and function of peripheral macrophage populations necessitates an increased understanding of the mechanisms by which functionally distinct macrophage populations arise as well as the ramifications of macrophage heterogeneity. The present review summarizes recent data which supports multiple mechanisms by which heterogeneous macrophage populations arise: 1) differential signals experienced within diverse tissue microenvironments; 2) developmentally-staged expression of specific functions; 3) clonal variation of myeloid progenitor cells; and 4) alternate hematopoietic stimulation. These data show that the above processes are not mutually exclusive and that each likely contributes to the observed heterogeneity of peripheral macrophage populations. PMID- 8501400 TI - "Stiff red cell syndrome". A review of the treatment of sickle cell disease with pentoxifylline. AB - Pentoxifylline has been used extensively to improve microcirculation, particularly in peripheral vascular disease. Pentoxifylline appears to act by increasing red cell flexibility and inhibiting platelet aggregation and white cell adhesion. For that reason, experimental and clinical studies were initiated to explore its possible usefulness in the prevention of vaso-occlusive crises in sickle cell diseases. The current status of such studies is reviewed. PMID- 8501401 TI - Determination of plasma volume and total blood volume using indocyanine green: a short review. AB - Rapid blood and plasma volume measurements gain increasing interest in order to avoid unnecessary blood transfusions. Only the indocyanine green method seems to satisfy the demand for a fast, safe and reproducible bedside method. We summarized older and newer experiences with this method, and also summarized the results for practical application. PMID- 8501402 TI - HLA class II antigens and interleukin-1 in patients affected by type-II diabetes mellitus and hyperlipemia. AB - In order to evaluate the influence of hyperlipemia on the specific cell defence reaction in type-II diabetes mellitus in humans, 20 diabetics were recruited in this study. They were divided into two groups on the basis of the absence or coexistence of abnormal serum lipid pattern. The lymphocyte and monocyte cells drawn from the type-II diabetic patients with abnormally elevated serum levels of cholesterol and triglycerides showed a decreased expression of major histocompatibility complex (MHC) class-II antigens and an impaired secretion of interleukin (IL-1). Values of MHC class-II antigen expression in diabetics without lipid metabolic alterations were not significantly different from those found in healthy subjects. In conclusion, abnormalities of lipid metabolism often found in type-II diabetes mellitus may play a key role in the impaired specific cell reaction toward infectious diseases of these patients. PMID- 8501403 TI - Correlation of function and energy metabolism in rat ischemic skeletal muscle by 31P-NMR spectroscopy: effects of torbafylline. AB - The aim of this study was to correlate function of rat ischemic skeletal muscle directly with energy metabolism, to investigate the effects of torbafylline, a novel xanthine derivative potentially useful for the treatment of peripheral vascular occlusive disease and other ailments of skeletal muscle, and to get insight into its mechanism of action. Phosphocreatine (PCr), inorganic phosphate (Pi) and pH were estimated at rest, during induced contractions and during the recovery phase after cessation of electrical stimulation in rat hind limb muscles with two weeks unilateral chronic ligation of the femoral artery. Concomitantly, contraction force was measured in terms of tension developed during the stimulation interval. The effects of torbafylline [7-ethoxymethyl-1-(5-hydroxy-5 methylhexyl)3-methylxanthine] on the above parameters were studied after chronic oral gavage (25 mg/kg body weight per day); treatment started the day after surgery and the last drug application was performed the day of the final experiments. Control animals received physiological saline under the same conditions. During rest no major differences could be detected either in PCr and Pi levels or in pH between the different muscles, ischemic or not and treated or not. During compelled contractions, PCr and pH decreased and Pi increased in all muscles. Differences between muscles and treatments emerged as the PCr drop was more pronounced in ischemic saline treated muscles and the Pi increase in drug treated muscles (normal and ischemic) were clearly less marked than in saline treated ones. Contraction force decreased rapidly during the 12 min electrical direct stimulation and fatigability increased from 67% in normal muscle to 88% in ischemic muscle. Drug treatment induced strikingly less fatigability as it was 44.5% in normal and only 62% in ischemic muscle. However, most marked differences in metabolite levels and pH were measured during the recovery period. As an indication of disturbed energy balance, the recovery of PCr, Pi and pH was seriously hampered in ischemic saline treated muscles; especially pH being still significantly decreased during the entire chosen recovery period of 15 min. Torbafylline not only restored function, but also helped the muscle recover faster and better from exhaustion, as all the parameters returned gradually to normal levels. PMID- 8501404 TI - Septo-optic dysplasia associated with polyendocrine dysfunction. AB - Septo-optic dysplasia (SOD) is a rare congenital disease that has been described in association with hypothalamic dysfunction. A case of polyendocrine dysfunction is described in a 22 year-old white female with septo-optic dysplasia. Findings included atrophic optic nerves, a cavum septum pellucidum and a small pituitary gland detected by magnetic resonance imaging. The patient had central diabetes insipidus, Hashimoto's thyroiditis, and gestational diabetes mellitus. A review of the literature is presented. A careful and detailed endocrine evaluation is needed in patients with SOD. PMID- 8501405 TI - Seckel's syndrome: a case report. AB - The authors describe a case similar to the complex syndrome described by Seckel (1960), "dwarf-headed dwarfism." This case differs from others previously reported because of slight hypophyseal hypoplasia with a slight reduction of human chorionic gonadotrophin (HCG) serum levels, and because of the parent's consanguinity (first cousins). A comparative critical examination was carried out on the 44 cases of Seckel's syndrome described in the literature. Only 19 of these cases appear to be comparable with Seckel's description, while the others are dubious, due to incomplete data. Some can be identified as ordinary cases of dwarfism with microcephaly or mental deficit. Until more precise and objective parameters are established, it would be advisable to refer to this particular form of dwarfism as "Virchow-Seckel type dwarf-headed dwarfism," in order to avoid using the more binding term "syndrome" and the misleading term "bird headed." PMID- 8501406 TI - The number of signals in multilead ECGs in individuals. AB - The number of independent signals in multilead electrocardiograms (ECGs) (body surface maps) of individuals have been determined by using two different methods. Both methods are based on an analysis of the eigenvalues of the spatial covariance matrix corresponding to the individual multilead ECG. One method takes only the noise level into account (threshold method). The other method is based on an information theoretic criterion (minimum description length) and uses explicitly the statistical properties of the noise (noise covariance). The analysis was performed on the QRS complexes and ST-T complexes of the multilead ECG of 61 subjects. The noise was estimated from three isoelectric intervals (PQ interval). For the different subjects, 0-14 signals (with a mean of 7 signals) were detected in the QRS interval and 0-9 signals (with a mean of 3 signals) were detected in the ST-T interval. PMID- 8501407 TI - Identification of patients with ventricular tachycardia after myocardial infarction by high-resolution magnetocardiography and electrocardiography. AB - The value of time domain analysis of late fields in the high-resolution magnetocardiogram in the identification of myocardial infarction patients with ventricular tachycardia was investigated in 30 subjects: 10 patients with documented sustained ventricular tachycardia and old myocardial infarction, 10 patients with old myocardial infarction without complex ventricular arrhythmias, and 10 normal volunteers. The duration of the QRS complex in the magnetocardiogram was significantly longer in ventricular tachycardia patients compared to myocardial infarction patients (144 (SD, 33) vs 109 (SD, 8) ms; p = 0.004). The root-mean-square field of the last 60 ms of the QRS complex was smaller in ventricular tachycardia patients than in myocardial infarction patients (830 (SD, 650) vs 1,480 (SD, 730) fT, respectively; p = 0.047). Also, the duration of the low-amplitude signal less than 700 fT was longer in ventricular tachycardia patients than in myocardial infarction patients (47 (SD, 28) vs 28 (SD, 8) ms, respectively; p = 0.048). The sensitivity and specificity in identifying ventricular tachycardia patients were both 80%, and the positive and negative predictive values were 78% and 86%, respectively. High-resolution electrocardiography recorded during the same session performed slightly better: sensitivity 90%, specificity 90%, and positive and negative predictive values 90%. The signal-to-noise ratio of electrocardiogram was higher (approximately 2 x) than that of magnetocardiogram. It is concluded that the new magnetocardiographic technique seems helpful in screening patients at risk of ventricular arrhythmias after myocardial infarction. The results encourage further refinement of the technique and application in prospective studies. PMID- 8501408 TI - Postexercise changes of the QTc interval in patients with recent myocardial infarction. AB - A lack of the QTc ratio decrease at maximal exercise is considered as an index of exercise-induced ischemia in patients with coronary artery disease. The authors studied 51 patients with recent myocardial infarction in order to evaluate the QTc changes with exercise in assessing the presence of remaining ischemic myocardium. All patients were submitted to exercise stress tests, coronary angiographies, and exercise thallium 201 scintigraphies within 3-5 months of the myocardial infarction. Of the patients studied, 18 showed one-vessel disease and 33 showed multivessel disease. All vessels were classified as patent or occluded. In all patients with reversible thallium 201 defects both at distance and in the infarct zone, the QTc interval following exercise either showed a prolongation or no change from the resting electrocardiogram. In patients with only fixed perfusion defects, the QTc shortened at the end of the test. This study showed a low sensitivity and specificity for inducible ST-segment depression compared with the delayed redistribution on the postexercise thallium 201 scintigram. QTc variations at the end of exercise electrocardiograms are valuable as a noninvasive, low-cost identification of residual ischemic myocardium in patients after myocardial infarction. PMID- 8501409 TI - Is silent ischemia on the routine admission ECG an important finding? AB - The authors' objective was to determine if, in the absence of known coronary artery disease, ST-T changes suggestive of silent ischemia on the admission electrocardiogram (ECG) identify a group of patients at high risk for cardiac event or death. A prospective cohort study was undertaken at the university hospital of a tertiary care center. All patients admitted to the hospital during the 5-month study period were screened. The authors found 54 patients with risk factors but no symptoms of coronary artery disease whose admission ECGs showed silent ischemia (ischemia group), and 71 patients with similar risk of coronary artery disease but without admission ECGs showing silent ischemia (control group). Three-week and 6-month incidences of angina, myocardial infarction, and death among patients in the silent ischemia and control groups were compared. Seven (13%) patients in the silent ischemia group had cardiac events or noncardiac death in the subsequent 3 weeks versus one (1%) noncardiac death in the control group (p < 0.02). At 6 months, eight (15%) patients in the silent ischemia group versus two (3%) in the control group had cardiac events (p = 0.02). It is concluded that among patients with risk factors but no symptoms of coronary artery disease, silent ischemia on the admission ECG is associated with an increased likelihood of short-term death or cardiac event. PMID- 8501410 TI - Assessment of global and regional myocardial function using the Minnesota Q/QS codes. A comparison with clinical ECG interpretation. AB - The authors investigated 244 consecutive patients with suspected coronary artery disease by coronary angiography and quantitative left ventriculography to compare the Minnesota Q/QS code (MC) with clinical electrocardiographic (ECG) interpretation. Patients who were suspected to have wall motion abnormalities for reasons other than coronary artery disease for possible regional wall motion abnormalities were excluded. Out of 244 patients, 159 (65%) had wall motion abnormalities. The sensitivity for detecting wall motion abnormalities was 21% for MC 1.1 and 51% for MC 1.1-3, whereas clinical ECG interpretation showed a sensitivity of 73%. Specificity for MC 1.1 was 93% and for MC 1.1-3 it was 84%. Specificity of clinical ECG interpretation (84%) was comparable. Compared to the MC, clinical ECG interpretation showed a stronger association with left ventricular ejection fraction, number of segments with abnormal wall motion, and severity of wall motion abnormality. Anterior myocardial infarction presented more often with clinical ECG changes (71%) and with a Q/QS code (50%) than inferior myocardial infarction (61% and 41%, respectively). In summary, in contrast to clinical ECG criteria, the MC has high specificity at the expense of a low sensitivity. PMID- 8501411 TI - Susceptibility of the right and left canine atria to fibrillation in hyperglycemia and hypoglycemia. AB - The objective of this study was to investigate the changes in the refractory period and in the susceptibility to fibrillation of canine atria associated with different levels of glycemia, and the differences in these parameters between the two atria. In 20 anesthetized, open-chest dogs weighing 24 kg, the effective refractory period was measured by atrial pacing with a run of 8 stimuli (S1-S1 350 ms) followed by a progressively earlier S2 until no stimulation of the atrial tissue occurred. The susceptibility to fibrillation was assessed by applying DC at 2, 3, and 4 V for 3 seconds, 7 times each, on the atrial appendage. If fibrillation occurred and persisted for 3 minutes, a transthoracic synchronized shock was delivered (200 J). The refractory period and the susceptibility to fibrillation were assessed under normoglycemia first, and then under hypo and hyperglycemia, in the right and left atrium successively, in random order. The incidence of induced atrial fibrillation in the right atrium was: hypoglycemia 31.96% (132 of 413 attempts); normoglycemia 24.11% (81 of 336; p < 0.05); and hyperglycemia 20.23% (85 of 420). Results for the left atrium were hypoglycemia 52.06% (215 of 413); normoglycemia 40.18% (135 of 336; p < 0.005); and hyperglycemia 32.86% (138 of 420; p < 0.05). Sustained atrial fibrillation (> 3 minutes) occurred significantly more often under hypo rather than hyperglycemia and stimulated the left rather than the right atrium. The refractory period was shortest under hypoglycemia in the left atrium and longest under normo or hyperglycemia in the right atrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501412 TI - T wave alternans associated with amiodarone. AB - T wave alternans is an intriguing phenomenon widely observed in some experimental conditions, but rare in clinics. The authors describe a case of T wave alternans associated with amiodarone treatment. This electrocardiographic finding spontaneously reverted and was not associated with ventricular arrhythmias or hemodynamic depression. Mechanisms that may be responsible for alternation of the T wave are discussed. PMID- 8501413 TI - Triple ventricular parasystole. AB - This presentation reflects the analysis of an electrocardiographic recording obtained from a patient with hypertensive heart disease. In the initial section of the tracing, fixed coupled monomorphic ectopic ventricular beats occurred in regular trigeminal rhythm. The pattern changed following an atrial extrasystole and several ventricular ectopic beats of various configuration occurred, often in sequence. Analysis demonstrated the presence of three independent parasystolic rhythms, two of which manifested with the character of intermittency, namely they were occasionally reset by extraneous impulses. The interplay of the sinus pacemaker with three parasystolic foci resulted in a very complex arrhythmic pattern. In some periods, however, two out of three ectopic rhythms were inapparent, and the third one manifested with fixed coupled complexes, so that a regular extrasystolic trigeminy ensued, and parasystole was not recognizable. PMID- 8501414 TI - Normal limits of derived vectorcardiogram in Chinese. AB - Derived vectorcardiograms from 503 healthy Chinese individuals (248 men and 255 women) were analyzed to determine the normal ranges of scalar and vector measurements in a Chinese population. In both sexes, the magnitude of the maximal spatial QRS and T vectors decreased significantly with age and was significantly smaller in women in all age groups. The results of this study were concordant with the results of previous studies using the Frank lead system in Caucasians, but the derived vectorcardiogram has the advantage of not requiring any leads additional to those used for recording the conventional 12-lead electrocardiogram. In conclusion, it was found that for healthy Chinese individuals there are significant age and sex related influences on the normal ranges of derived vectorcardiograms. Therefore, vectorcardiographic diagnostic criteria for Chinese individuals should be age-related and sex-related. PMID- 8501415 TI - New trends in the diagnosis and treatment of cardiac arrhythmias. PMID- 8501416 TI - Amiodarone and the thyroid: pharmacological, toxic and therapeutic effects. PMID- 8501417 TI - Sporadic distal renal tubular acidosis and periodic hypokalaemic paralysis in Kashmir. AB - Twenty-one cases of renal tubular acidosis presenting with periodic hypokalaemic muscular weakness, that were seen over an 8-year period, are presented. The biochemical features suggested a diagnosis of distal renal tubular acidosis and absence of family history with negative screening of eighteen families pointed towards the primary sporadic nature of the disorder in nineteen of the cases. Alkali and replacement potassium therapy resulted in immediate and sustained clinical recovery in all the cases. PMID- 8501418 TI - Deficiency of erythropoietin is not responsible for the anaemia associated with cyclosporin treatment of insulin-dependent diabetes mellitus. Canadian-European Randomized Control Trial Group. AB - OBJECTIVES: To explore the possible pathogenetic role of erythropoietin (EPO) in the anaemia associated with cyclosporin (Cs) in newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM). DESIGN: A multicentre randomized placebo controlled prospective trial of Cs immunosuppression for 12 months in IDDM patients. SETTING: Patients were recruited from the out-patient clinics of diabetes centres in Europe and Canada. SUBJECTS: Patients 9-35 years old with a clinical diagnosis of ketonuric IDDM entering less than 6 weeks after diagnosis. 188 patients were originally recruited; 105 patients completed the investigation, 52 patients being treated with Cs, and 53 patients receiving placebo. INTERVENTIONS: Random allocation to receive either Cs or placebo. The initial dose of Cs was 10 mg kg-1 BW day-1. Therapy was maintained for 12 months. MAIN OUTCOME MEASURES: B-Haemoglobin, s-creatinine, and s-EPO concentrations were monitored before, during and after therapy with either Cs or placebo. RESULTS: Blood-haemoglobin (Hgb) fell from 8.5 +/- 0.8 to a nadir of 7.8 +/- 0.9 mmol l-1 at 6 months (P < 0.0001) in IDDM patients treated with Cs but not in the placebo patients (8.5 +/- 0.8 to 8.8 +/- 0.9 mmol l-1, NS). The mean serum EPO levels remained unaltered throughout the 6-month period of Cs and placebo therapy. No significant differences in serum EPO levels between Cs and placebo-treated diabetic patients were found after 6 months of treatment. CONCLUSIONS: The light anaemia associated with Cs therapy in IDDM patients is not related to an insufficient production of EPO, but is caused by other, as yet unknown mechanisms, unrelated to the nephrotoxic action of this drug. PMID- 8501419 TI - Long-term prognosis for diabetic patients with foot ulcers. AB - OBJECTIVE: To evaluate the recurrence of foot ulcers as well as the cumulative amputation and mortality rates in diabetic patients with previous foot ulcers. DESIGN: A prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer with a median follow-up of 4 years. SETTING: A multidisciplinary foot-care team. POPULATION: Five-hundred-and-fifty-eight consecutive diabetic patients with foot ulcers treated between 1 July 1983 and 31 December 1990 were followed to final outcome. Out of these patients, 468 healed either primarily (n = 345) or after minor or major amputations (n = 123) and 90 died before healing had occurred. Those 468 patients who healed were included in this prospective study from the time of healing. MAIN OUTCOME MEASURES: Patients were followed according to a standardized protocol with registration of foot lesions, amputation, morbidity and mortality. Clinical examination was performed twice yearly. RESULTS: After 1, 3 and 5 years of observation 34%, 61% and 70% of the patients, respectively, had developed a new foot ulcer. The recurrence rate of foot lesions was slightly higher among patients who previously had had an amputation (P < 0.05, P < 0.01 and non-significant, respectively). Among patients with previous primary healing the cumulative amputation rates were 3%, 10% and 12% after 1, 3 and 5 years of follow-up compared with 13%, 35% and 48% among those who previously healed after amputation, irrespective of previous amputation level (P < 0.001 at all time points). All amputations except three were initiated by a foot ulcer deteriorating to deep infection or progressive gangrene. The long-term survival ratio was lower among patients healed after previous amputation (80%, 59%, 27%) compared with patients with previously primary healing (92%, 73%, 58%) after 1, 3 and 5 years of observation, respectively (P < 0.001, P < 0.01 and P < 0.001 respectively). The mortality rate was twice as high among primarily healed and four times as high among patients with amputation compared to an age- and sex matched Swedish population. CONCLUSION: These findings stress the need for life long surveillance of the diabetic foot at risk and the necessity of preventive foot care among diabetic patients with previous foot lesions, and particularly among those who had had a previous amputation. PMID- 8501420 TI - Reversal of apparent AIDS dementia complex following treatment with vitamin B12. AB - The human immunodeficiency virus (HIV)-associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B12 levels occur in up to 20% of patients with acquired immune deficiency syndrome (AIDS) and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. We describe a patient with AIDS who presented with an apparent advanced AIDS dementia complex. There was an associated low serum vitamin B12 resulting from malabsorption due to low gastric intrinsic factor secretion. Following treatment with vitamin B12 the symptoms resolved over a 2-month period. We believe that the AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B12 deficiency. PMID- 8501421 TI - GM-CSF in the treatment of a patient with severe methotrexate intoxication. AB - This case report describes the successful treatment of severe methotrexate intoxication in a 72-year-old female patient. Following two prior uneventful courses of a polychemotherapy regimen including low-dose intravenous (i.v.) methotrexate, the patient presented with fever, polymucositis, incipient pyodermia, acute renal failure and pancytopenia 9 days after the third application. Severe methotrexate overdose was confirmed by serum levels. Using a polypragmatic treatment approach focusing on renal function and including granulocyte-macrophage-colony-stimulating factor (GM-CSF) this life threatening and nearly fatal intoxication was successfully treated. This case report demonstrates that GM-CSF might contribute to rapid reconstitution of leukopoiesis once methotrexate serum levels are in the subtoxic range. PMID- 8501422 TI - Insulin and left ventricular hypertrophy. PMID- 8501423 TI - The relations of empathy-related emotions and maternal practices to children's comforting behavior. AB - Examined are the relations of maternal empathy-related characteristics, maternal child-rearing practices, and children's vicarious emotional responding to kindergarteners' and third graders' comforting of a crying infant. Children who exhibited facial personal distress in reaction to the baby cry were less likely to help than were other children. In addition, children's distressed reactions to a different sympathy stimulus (a film) were positively correlated with their distressed reaction to the baby cry; children's self-reported reactions to the sympathy-inducing film also were related to their comforting behavior. For girls, maternal perspective taking was positively related to amount and quality (tone of voice) of comforting behavior. Moreover, maternal use of problem-solving and discussion when their daughters were distressed or anxious were associated with higher levels of girls' helping whereas maternal comforting/affirming in a distressing context was negatively related to helping. The only relation of maternal variables to comforting for boys was a positive correlation between maternal reinforcement and quality of boys' comforting. PMID- 8501424 TI - The relation of mothers' controlling vocalizations to children's intrinsic motivation. AB - Twenty-six mother-child dyads played together in a laboratory setting. Play sessions were surreptitiously videotaped (with mothers' permission), and each maternal vocalization was transcribed and coded, first into 1 of 24 categories and then ipso facto into one of three supercategories--namely, controlling, autonomy supportive, and neutral. The degree of mothers' controllingness was calculated as the percentage of vocalizations coded as controlling. This index was correlated with the intrinsic motivation of their 6- or 7-year-old children, as assessed primarily by the free-choice behavioral measure and secondarily by a child self-report measure of interest and liking for the task. Both correlations were significantly negative, thereby suggesting that the robust laboratory findings of a negative relation between controlling contexts and individuals' intrinsic motivation are directly generalizable to the domain of parenting. Results are discussed in terms of the processes that undermine intrinsic motivation and the means through which parental controllingness is communicated. PMID- 8501425 TI - Trait confirmation and disconfirmation: the development of attribution biases. AB - In the present study, a new method for conducting person perception research, the confirmability paradigm, was adapted for use with children. In the confirmability paradigm subjects are asked how many behaviors they require before attributing positive and negative traits to other people. This new procedure was used to study developmental differences in the amount of information required for trait inference, as well as negativity and egocentric biases in trait attribution. Subjects were 70 children in grades 3 through 5 and 46 college students. The study revealed that traits differ in the amount of behavioral information required for their inference. In addition, a developmental decrease in attribution criteria was detected for various traits. Evidence for a negativity bias in the attribution of several traits was also obtained. Subjects exhibited an egocentric bias in their trait ratings but not in their attribution criteria. The utility of this new approach for the study of person perception is discussed. PMID- 8501426 TI - Children's coping in self- and other-relevant contexts. AB - The purpose of this study was to examine children's coping strategies in situations in which negative events befall the children themselves and contexts in which children observe others in negative situations. Kindergarten and second grade children and their mothers were interviewed about the children's coping strategies in distressing self- or other-relevant contexts (e.g., when the children themselves were socially rejected or when they observed a peer being rejected). According to both child and maternal reports, children were particularly likely to use instrumental coping strategies when they observed another child's distress; they appeared to prefer distracting and avoidant actions, crying, or support from others when they themselves experienced distress. With age, there also was evidence of a decrease in the use of support related strategies, and increases in cognitive restructuring, cognitive avoidance, and direct problem-solving. Several sex differences consistent with gender stereotypes also were noted. PMID- 8501427 TI - Mexican-American mothers' socialization strategies: effects of education, acculturation, and health locus of control. AB - The present study examined maternal education, acculturation, and health locus of control beliefs in relation to parenting strategies that promote the internalization of healthy eating habits in Mexican-American children. Eighty low income Mexican-American mothers and their 4- to 8-year-old children participated in the study. Mother-child interactions during dinner were observed, and mothers were interviewed about the socialization strategies they used to influence their children's food consumption. Results indicated that mothers with more external health locus of control beliefs were less likely to use socialization techniques associated with internalization. Acculturation was negatively related to the use of internalization techniques, with less traditional mothers using more directive strategies. Education did not predict maternal behavior after controlling for health locus of control beliefs. PMID- 8501428 TI - Adolescent risk-taking: an analysis of problem behaviors in problem children. AB - In this study adolescent risk-taking is explored from several theoretical positions: Jessor's problem-behavior perspective, risk-taking as normal and adaptive, adolescent egocentrism, and a decision-making perspective. Adolescents (ages 11-17) referred to mental health clinics (N = 80) completed a risk involvement and perception questionnaire, the Jesness Personality Inventory, and a measure of adolescent egocentrism. For purposes of concurrent validity, a diagnosis was completed by the subject's clinic therapist. As predicted, both Benefit and Risk Perception were significantly correlated with Involvement (in opposite directions), supportive of a decision-making perspective. A configuration of social maladjustment personality correlates in conjunction with a diagnosis of Conduct Disorder showed a strong, positive correlation with Involvement, supporting a problem-behavior perspective. Egocentrism measures were not significantly related to Risk Involvement or Risk and Benefit Perceptions. Adolescent risk-taking is argued to be a multidimensional phenomenon involving personality correlates and cognitive aspects of decision-making. PMID- 8501429 TI - Verb-specific constraints in sentence processing: separating effects of lexical preference from garden-paths. AB - Immediate effects of verb-specific syntactic (subcategorization) information were found in a cross-modal naming experiment, a self-paced reading experiment, and an experiment in which eye movements were monitored. In the reading studies, syntactic misanalysis effects in sentence complements (e.g., "The student forgot the solution was...") occurred at the verb in the complement (e.g., was) for matrix verbs typically used with noun phrase complements but not for verbs typically used with sentence complements. In addition, a complementizer effect for sentence-complement-biased verbs was not due to syntactic misanalysis but was correlated with how strongly a particular verb prefers to be followed by the complementizer that. The results support models that make immediate use of lexically specific constraints, especially constraint-based models, but are problematic for lexical filtering models. PMID- 8501430 TI - Reinstatement of causal information during reading. AB - An on-line word naming probe was used to test whether information presented earlier in a text, and then backgrounded by several sentences, would be reinstated when Ss were required to understand the cause of a currently processed action or event. In Experiment 1, Ss named a probe word that represented an earlier-mentioned cause more quickly when it followed a causal coherence break than when it followed a neutral sentence. Experiments 2 and 3 replicated this effect and examined 2 conditions that may affect the process of reinstating a cause: (a) Inclusion of part of the context in which the cause was originally presented was not necessary to obtain reinstatement of the cause and (b) reinstatement of the cause was not evidenced when it had been disconfirmed earlier in the text. PMID- 8501431 TI - Memory-based automaticity in the discrimination of visual numerosity. AB - In the development of memory-based models of automaticity, it is crucial to specify the nature of the memory representation. Seven experiments with 94 students use a counting task to determine whether a feature (i.e., identity, color, or orientation) is explicitly represented in memory. It is assumed that the degree of transfer to a pattern differing on one feature is determined by that feature's importance in supporting skilled performance. Experiment 1 determined the practice necessary to obtain automaticity. In Experiments 2a, 3a, and 4a, which investigated the nature of the representation after extended practice, changing neither the identity nor color of elements had strong effects on transfer, but changing pattern orientation did impair memory retrieval, thus suggesting that for the counting task, pattern orientation is more important than element identity or color. Experiments 2b, 3b, and 4b replicated these results after limited practice. PMID- 8501432 TI - Modeling intrusions and correct recall in episodic memory: adult age differences in encoding of list context. AB - A model for correct recall and intrusions in cued recall of word lists is introduced. Intrusions are false responses that were correct in an earlier list. The model assumes 3 exclusive states for memory traces after encoding: with a list tag (i.e., with information about list origin), without list tags, and missing. Across lists, a trace can lose its list tag or its content. For retrieval, an optimal strategy of response selection was assumed. Younger and older laboratory-trained mnemonists participated in 2 experiments in which recall of permutations of a single word list across a single set of cues was held constant with individually adjusted presentation times. With correct recall equated to younger adults, older adults were more susceptible to intrusions. Age differences were restricted to model parameters estimating the probability of generation of list tags. Alternative accounts of age differences in context memory are discussed. PMID- 8501433 TI - Speed versus accuracy instructions, study time, and the mirror effect. AB - Attention/likelihood theory is a model of recognition memory designed to explain the mirror effect (Glanzer & Adams, 1985, 1990). The theory and the effect were studied using speed versus accuracy instructions and short versus long exposure of stimuli. Speed versus accuracy instructions during test and short versus long exposure of stimuli during study were used to vary the number of features sampled from stimuli. When the number of features sampled was reduced either by speed instructions or by shorter exposure, recognition performance was impaired. The theory predicts that in such cases, all distances between underlying distributions will contract. That means, moreover, that when recognition accuracy is decreased for old stimuli, it is also decreased for new stimuli. These predictions were supported by the data from three experiments. PMID- 8501434 TI - Eliciting cryptomnesia: unconscious plagiarism in a puzzle task. AB - In three experiments we investigated cryptomnesia (unconscious plagiarism) and source memory using a word-search puzzle task. Subjects first alternated with a "computer partner" in locating words from 4 puzzles. They then attempted to recall their previously generated items as well as to locate additional new words. Substantially more plagiarism was committed in these tasks than was observed in a study by A. S. Brown and D. R. Murphy (1989), in which Ss generated category exemplars. Manipulations of retention interval (Experiment 1) and degree of encoding (Experiments 2a and 2b) reliably influenced plagiarism rates. Source confusions from a modified recognition memory task (Experiment 3) were used as the basis for a unitary relative strength model to explain both source and occurrence (item) forgetting. PMID- 8501435 TI - Steroid metabolism in the cortex and the medulla of the early fetal bovine ovary. AB - Suspensions of cells obtained from the cortex and the medulla of the ovary of early bovine fetuses of 4-10 cm in crown-rump (C-R) length were used for studies of the metabolism of radiolabeled exogenous steroid precursors. Tritiated dehydroepiandrosterone, androstenedione, and testosterone were employed as precursors and their metabolic products were evaluated after separation by thin layer chromatography. The extent of conversion of tritiated dehydroepiandrosterone to androstenedione was higher in cells from medulla than in those from the cortex. Androstenedione was metabolized mainly to estrone, and the percent of transformation was similar in the cortex and the medulla, but the rate of formation of 17 beta-estradiol was higher in the medulla than in the cortex. Furthermore, cells obtained from the cortex and the medulla aromatized testosterone to 17 beta-estradiol at a similar rate. In all cases, the percent of transformation was higher in ovaries from fetuses of 4.0 cm in C-R length than those from fetuses of 9.0-10.0 cm in C-R length. These data suggest that, in the bovine fetal ovary, the activity of 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 beta-hydroxysteroid dehydrogenase predominates in the medulla, whereas aromatase activity is similar in the cortex and the medulla of the early fetal bovine ovary. PMID- 8501437 TI - The mechanism of gastrulation in the white sturgeon. AB - Gastrulation in the white sturgeon, Acipenser transmontanus, involves many of the same processes as in the amphibian Xenopus laevis, but the timing and relative importance of these processes are altered so that they function appropriately in a different type of egg. In both species, convergence and extension result from a combination of radial and mediolateral cell intercalation. In sturgeons, where the blastopore lip forms at the equator, an early phase of thinning and extension of the animal cap moves the marginal zone below the equator during late blastula and early gastrula stages. This early extension without convergence is followed by convergent extension of the dorsal marginal zone after its displacement vegetally. When the animal cap is removed before gastrulation, precluding the initial extension that moves the marginal zone below the equator, autonomous convergence of the lower marginal zone produces an equatorially constricted embryo. Dorsal explants of sturgeon embryos undergo convergent extension similar to that documented in Xenopus (Keller and Danilchik: Development, 103:193-209, 1988), with distinct zones of extension in the involuting and non-involuting marginal zone regions. The extension of cultured explants demonstrates that this morphogenetic behavior is intrinsic to the dorsal tissue. These results show that normal gastrulation depends not only on the function of these independent morphogenetic mechanisms, but also on their mechanical context in the embryo. Experimental analyses and comparison of gastrulation in similar embryos, such as those of Xenopus and sturgeons, reveal both common developmental mechanisms, and variation in their roles. PMID- 8501436 TI - Gastrulation and mesoderm morphogenesis in the white sturgeon. AB - This study presents a detailed description of gastrulation in the white sturgeon, Acipenser transmontanus, using scanning electron microscopy, histology, and time lapse filming and video microscopy. This morphological analysis describes the similarity of gastrula structure in the sturgeon and the amphibian Xenopus laevis, and suggests that the species share many developmental mechanisms. It also identifies important differences, such as the equatorial dorsal lip in sturgeon, and provides a basis for interpreting experiments that test the effect of these differences on gastrulation. The onset of gastrulation in the sturgeon is marked by the appearance of a blastoporal equatorial pigment line that forms as the apices of bottle cells contract and concentrate surface pigment granules. Bottle cell formation at the blastopore lip and involution of surface material through the blastopore are strikingly similar to the equivalent processes in amphibian embryos. As gastrulation continues, a distinct cleft of Brachet forms between pre-involution and post-involution material. Following involution, the prospective axial mesoderm located on the dorsal surface of the late blastula (Ballard and Ginsburg: J. Exp. Zool., 213:69-103, 1980) ingresses from a central zone in the posterior archenteron roof surface in a process that is unlike any in Xenopus, but resembles events in other amphibians (Purcell, 1992; Smith: Dev. Biol., 98:250-254, 1983; King: Biol. Bull., 4:287-300, 1903). The detailed comparison of similarities and differences in gastrulation in different vertebrate lineages yields insights into the function and versatility of common developmental mechanisms. PMID- 8501438 TI - Effect of follicle cells and steroidogenesis on maturation and fertilization in vitro of pig oocytes. AB - Follicle cell numbers, steroidogenesis, and culture conditions were manipulated in a series of experiments designed to identify their effect during in vitro maturation of pig oocytes upon meiotic cycle progression, sperm penetration and male pronuclear formation. In Experiment 1 a static culture system was used to determine the effect of follicle cell numbers on maturation. When the follicle cell number was 3.5 x 10(3) cells per complex or less, cell cycle progression to metaphase II (M-II) and male pronuclear formation were both low (< 30%). Increasing follicle cell numbers to 15 x 10(3) per complex significantly enhanced both meiotic maturation (93%) and male pronuclear formation (83%). A further 10 fold increase in follicle cell numbers (150 x 10(3)), however, reduced subsequent male pronuclear formation (33%). The purpose of Experiment 2 was to determine whether the observed follicle cell effects were influenced by the type of culture system used for oocyte maturation. Comparisons were made between both static and non-static forms of culture. Meiotic progression was significantly depressed when non-static culture systems were used for the maturation of oocyte-cumulus complexes containing low numbers of somatic cells (< 15 x 10(3) cells). However, the addition of somatic cells (follicle shells) to non-static, but not static, culture systems significantly enhanced male pronuclear formation in all groups irrespective of the number of cumulus cells in the oocyte complex. Experiment 3 investigated the effects of the steroid environment on maturation and male pronuclear formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501439 TI - Metamorphosis-dependent recognition of larval skin as non-self by inbred adult frogs (Xenopus laevis). AB - Larval cells in tissues of the anuran tadpole are replaced by adult cells in the corresponding tissue of the frog during metamorphosis. As an extreme example of such replacement, tissues of the tail, which have no counterpart in the adult, are completely eliminated during metamorphosis. We postulated that some immunological recognition mechanism might be involved in this specific elimination of the tail tissue. Our working hypothesis was tested by applying the skin transplantation technique to individuals of the inbred J strain of Xenopus laevis, which accept homografts. We demonstrated that young adults reject skin grafts from larvae. This rejection was immunological in nature because the secondary response of rejection was observed. There was a clear difference in graft rejection between grafts from the tail and those from the body. Grafts of tail skin were rejected irrespective of the metamorphic stages of donors. By contrast, grafts of body skin became acceptable as donors metamorphosed. The mean survival time of the larval skin was much longer than that of major histocompatibility complex (MHC)-disparate skin grafts reported by other investigators, suggesting that the rejection described in the present study is due to disparity in minor histocompatible (minor-H) antigens. We propose the involvement of the immunological recognition mechanism in the process of specific detection and elimination of larval cells in the tail. PMID- 8501440 TI - Rate of establishment of a fertilising population of spermatozoa in the sheep cervix after a single mating at the onset of oestrus. AB - In order to study how soon a population of spermatozoa capable of fertilisation could progress into the cervical canal, the vaginal contents were flushed with a detergent solution at different intervals after mating at the onset of oestrus. Eggs recovered 1 or 2 days later from the oviducts were stained and examined by phase-contrast microscopy. Flushing at 3 minutes after mating did not prevent fertilisation in 44% of instances, whereas similar flushes performed at 6 or 9 minutes completely prevented fertilisation in a total of 26 animals. In the groups flushed at 12 and 15 minutes, the proportion of eggs fertilised was 21% and 24%, respectively, and this increased to 37% after flushing at 18 minutes. An explanation is offered for the paradoxical finding at 3 minutes, and it is concluded that at least 30-60 minutes would be required for adequate colonisation of the cervix with a fertilising population of spermatozoa under the conditions employed in the experiment. However, multiple matings or mating closer to the time of ovulation might act to reduce this interval. PMID- 8501441 TI - Role of prolactin and the gonads in seasonal physiological changes in the collared lemming (Dicrostonyx groenlandicus). AB - On a seasonal basis, collared lemmings undergo a number of physiological and morphological changes. Short photoperiod exposure results in a molt to a white pelage, an increase in body weight, a reduction in relative body fat content, an increase in relative water content, and the development of a bifid claw. Treatment with the dopamine agonist, CB-154, resulted in a reduction in serum prolactin and the development of the white pelage in lemmings housed under 16L:8D, while treatment with the dopamine antagonist, sulpiride, prevented the winter molt in animals transferred to 8L:16D. Castration under 16L:8D resulted in an increase in body weight and an enlargement of the bifid claw. Castrated animals also molted more readily when treated with CB-154 and developed a relatively greater carcass water content. Treatment with CB-154 increased relative carcass fat content. These findings suggest that, in the collared lemming, seasonal changes in pelage parameters are regulated by prolactin, with gonadal hormones playing a modulating role. Body weight, water content, and bifid claw size appear to be influenced by gonadal hormones. PMID- 8501442 TI - Prevalence and incidence of schizophrenic disorders in Portogruaro. An Italian case register study. AB - The authors report a study of treated prevalence and incidence of schizophrenic and related functional psychoses in an area of northeastern Italy (Portogruaro), based on case-register data. Point, 1-year, and lifetime prevalence as well as incidence rates on the adult population for a broad ICD-9 diagnosis of schizophrenia are given. Data over an 8-year period show the incidence around .2/1000, point prevalence around 1.4, 1-year prevalence of 2.7, and lifetime prevalence around 5.2. The rates peak in the 45 to 64 age group on all measures of prevalence. The implications of these findings are discussed in the light of methodological issues in epidemiological studies of schizophrenia and comparisons are made with figures from other countries. PMID- 8501443 TI - Laughter in a psychiatric ward. Somatic, emotional, social, and clinical influences on schizophrenic patients. AB - The study was designed to explore the potential therapeutic effects of humor on hospitalized schizophrenics. For this purpose, in the first stage, we conducted a review of findings in regard to physical health, emotions, psychiatric state, and social behavior. In the second stage, we carried out an experiment with 34 resident patients in two chronic schizophrenic wards who were exposed to 70 movies during 3 months. The experimental group was exposed to humorous movies only, and the control group to different kinds of movies. Before and after the exposure to films for 3 months, both groups were tested on different health, emotional, social, and clinical measures using the Cognitive Orientation of Health Questionnaire, the Shalvata Symptom Rating Scale, blood pressure, heart rate, Perceived Verbal and Motor Aggression (rated by nurses), the Multiple Affect Adjective Check List, the Social Support Questionnaire 6, and the Brief Psychiatric Rating Scale (BPRS; rated by psychiatrists). Covariance analyses yielded significant reductions in Perceived Verbal Hostility, BPRS scales (total score, anxiety/depression), and significant increases in BPRS (activation) and degree of staff support experienced by the patients. The results indicate that the effects of exposure to humor may be mediated by the effects on the staff of the incidental exposure to humorous films. PMID- 8501445 TI - Allusive thinking in parents of schizophrenics. Meta-analysis. AB - Romney (J. Nerv. Ment. Dis. 178:481-486, 1990) performed a meta-analysis of studies examining psychometrically assessed "thought disorder" in the relatives of schizophrenics. He concluded that thought disorder was more prevalent in the relatives of schizophrenics than control subjects. The present review focuses on only those studies that measured "allusive thinking" using the Lovibond-Rapaport Object Sorting Test in parents of schizophrenics. Even when the meta-analysis included this more limited number of studies, it demonstrated that the parents of schizophrenics were 2.42 times more likely to obtain high scores on the Object Sorting Test, confirming replication of the original McConaghy (J. Neurol. Neurosurg. Psychiatry 22:243-246, 1959) finding. This effect remained significant when the original study was excluded from the meta-analysis. The predictive strength of parental Object Sorting Test score as a familial risk factor for the development of schizophrenia is discussed. PMID- 8501444 TI - Heredity and environment in schizophrenia, revisited. The contribution of twin and high-risk studies. AB - Life history study of monozygotic (MZ) twins discordant for schizophrenia led to the 1967 hypothesis that phenotypic schizophrenia was an expression of genotypic vulnerability interacting with prenatal and/or perinatal environmental experience. This report is a selected review of partial answers to five questions facing research efforts that have attempted to clarify the interactive gene environment model of schizophrenia. Follow-up study of the offspring of MZ twins with a diagnosis of schizophrenia and their MZ co-twins without schizophrenia demonstrated equal rates of schizophrenia; hence, each group of offspring carried equal genetic vulnerability for schizophrenia. Magnetic resonance imaging study of MZ discordant twins found that phenotypic schizophrenia was characterized by brain ventricular enlargement and hippocampal reduction in 87-93% of the schizophrenic twins, when compared with their nonschizophrenic co-twins. A longitudinal study of teenage children at differential risk for schizophrenia showed that brain ventricular enlargement in adulthood correlated significantly and positively with genetic risk for schizophrenia and number of perinatal complications, and negatively with birth weight. Significantly greater dysmorphological hand skin signs among schizophrenic MZ twins when compared with their nonschizophrenic co-twins have suggested an in utero second trimester fetal developmental abnormality for the schizophrenic subjects. Simultaneous neuroanatomic, neurophysiological, and neurocognitive evaluation of MZ twin pairs discordant for schizophrenia demonstrated decreased prefrontal physiological cerebral blood flow activation during Wisconsin Card Sorting Test for affected twins correlated with decreased hippocampal volume determined by magnetic resonance imaging. These neurocognitive studies have suggested that schizophrenia involves neocortical-limbic pathology and dysfunction implicated in performance of cognitive tasks requiring working memory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501446 TI - Coping and illness behavior among young adults with panic. AB - The present study investigated illness behavior and coping strategies among young adults with panic (N = 21), with other anxiety disorders (N = 27), and without anxiety disorders (controls; N = 296). The sample represented a cross-section of 29- to 30-year-old adults from the canton of Zurich in Switzerland. Coping was defined as the ways in which subjects react to life stress. Illness behavior was defined as use of medical care and substance consumption. Subjects with panic differed significantly from subjects with other anxiety disorders and controls in their coping strategies by seeking social support, using cognitive avoidance, and using rumination more frequently. Cognitive avoidance and rumination, however, are ineffective and maladaptive ways of dealing with stress. With respect to illness behavior, we found fewer differences. Subjects with panic had more psychiatric consultations and more days off from work than controls, but otherwise, they did not use medical care excessively. Also, their consumption of psychoactive substances was minimal, with the exception of tranquilizers. There was no indication of excessive use of nonpsychiatric medical care. The possible implications of these findings for psychotherapy and diagnostics are discussed. PMID- 8501447 TI - Sensation seeking and novelty seeking. Are they the same? AB - Responses to Zuckerman's Sensation Seeking Scale (SSS) and Cloninger's Tridimensional Personality Questionnaire (which consists of novelty seeking, harm avoidance, and reward-dependence dimensions) have been linked to a variety of behavioral and psychiatric variables. The relationship of these two measures to one another has not been examined previously and, in the present study, is evaluated in a group of men briefly hospitalized for treatment of alcohol and chemical dependence. Total sensation seeking scale scores were significantly correlated (Pearson r) with total novelty seeking scale scores. Set correlation analysis revealed significant overall relationships between sensation seeking and both high novelty seeking and low harm avoidance. Most of these overall relationships were attributable to six subscales, although broad relationships were observed between the SSS disinhibition and novelty seeking subscales, and between a harm avoidance subscale and all SSS subscales. Neither statistical approach identified an association between reward dependence and sensation seeking. PMID- 8501448 TI - Antisocial personality disorder among drug abusers. Relations to other personality diagnoses and the five-factor model of personality. AB - Antisocial personality disorder among drug abusers has been associated with poor drug abuse treatment outcome and greater human immunodeficiency virus infection risk compared with drug abusers without the disorder. Despite this, less is known about the personality trait dimensions of antisocial drug abusers, or about the prevalence of axis II comorbidity among this group. Similarly, little is known about the personality trait dimensions of antisocial drug abusers compared with those with axis II diagnoses other than antisocial or those with no personality diagnosis. The present study compared the personality traits of 203 outpatient opioid drug abusers categorized into either a pure antisocial group (i.e., antisocial diagnosis only), mixed antisocial group (i.e., antisocial plus another axis II diagnosis), other axis II group (i.e., axis II diagnosis other than antisocial), or a non-axis II group. Psychiatric diagnoses were made using a structured interview and personality traits of the four groups were compared using a self-report measure of the five-factor model of personality. As predicted, the mixed group was significantly more prone to neuroticism compared with the pure group, with higher scores on the vulnerability to stress and hostility facets. The mixed group also had a greater score on the neuroticism domain compared with the non-axis II group, with higher scores on five of the six facets. Significant differences were also found on agreeableness. The mixed group had lower scores on this domain (i.e., had higher interpersonal antagonism) compared with the non-axis II group. Somewhat surprisingly, the agreeableness score for the pure group was not significantly different from those of the remaining three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501449 TI - Dream-disturbed sleep in insomnia and narcolepsy. AB - Both patients with narcolepsy and insomnia frequently present clinically with nocturnal sleep disrupted by disturbing dreams. Polysomnographic correlates of these reports are unclear. In this study, 24 patients with psychophysiological insomnia and 16 patients with narcolepsy were compared on selected polysomnographic and self-reported typical dream characteristics. As a group, patients with narcolepsy showed more frightening, recurrent dreams and shorter rapid eye movement (REM) segments when compared with patients with insomnia. However, within the narcolepsy group, there were few correlations between typical dream characteristics and any measure of REM segment length or REM density. In the insomnia group, shorter REM segments and higher REM density were related to typically more vivid, frightening, and disrupted dreaming. We speculate that the mechanisms of disturbed dream recall may be different in insomnia and narcolepsy. PMID- 8501450 TI - Cognitive impairment related to conversion disorder: a two-year follow-up study. PMID- 8501451 TI - Electroencephalographic concomitants of a caffeine-induced panic reaction. PMID- 8501452 TI - Premenstrual mania: two case reports. PMID- 8501453 TI - Obsessive-compulsive disorder onset after removal of a brain tumor. PMID- 8501454 TI - Implicit perception, implicit memory, and the recovery of unconscious material in psychotherapy. AB - A review of the empirical literature on implicit perception and implicit memory reveals that Freud's hypotheses regarding free association, transference, and the recovery of unconscious material in therapy were correct in some areas and incorrect in others. Empirical evidence confirms that--as Freud hypothesized- when implicit (i.e., unconscious) perceptions and memories are made explicit (i.e., conscious), individuals are able to make more logical, realistic judgments and inferences regarding those perceptions and memories. However, empirical evidence does not support Freud's contention that free association is a particularly powerful tool for accessing unconscious material. The implications of these findings for psychoanalytic theory and therapy are discussed, and alternative approaches to accessing unconscious material in psychotherapy are described. PMID- 8501455 TI - How sound is the double-blind design for evaluating psychotropic drugs? AB - Sufficient data have accumulated to raise serious doubts about the integrity of the double-blind design that is presumed to shield psychotropic drug trials from bias and expectations. A major deficit in most drug trials has been the use of inert rather than active placebos. The deficiencies of the double-blind paradigm call for a questioning stance with respect to previous studies of psychotropic drug efficacy. Various possible ways of strengthening the double-blind paradigm are reviewed. PMID- 8501456 TI - Parental psychopathology and disorders in offspring. A study of relatives of drug abusers. AB - Associations between psychopathology among parents and among their offspring were examined among families of drug abusers. Patterns of transmission of disorders were examined in the context of several potential moderator variables, including gender of parent, ethnicity, and type of drug abused by the proband relative. The sample consisted of 492 parents and 673 siblings of cocaine abusers, and 400 parents and 476 siblings of opioid addicts. Results indicated that a) maternal depression was associated with several psychiatric disorders among all groups of offspring; b) paternal alcoholism yielded less powerful effects, showing associations with offspring substance abuse among blacks but not Caucasians; c) incidence of disorders among offspring showed sequential increases depending on whether neither, one, or both parents were affected; and d) there was little evidence for specificity of aggregation of disorders among these families. Results are discussed in terms of implications for empirical studies as well as intervention programming. PMID- 8501457 TI - Buprenorphine versus methadone maintenance for opioid dependence. AB - Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501458 TI - Live and learn: patient education delays the need to initiate renal replacement therapy in end-stage renal disease. AB - During a longitudinal study of the quality of life of end-stage renal disease, 204 patients with deteriorating renal function were identified before dialysis or transplantation was required to preserve their lives. These patients were randomly assigned to either an enhanced or a standard education condition. The enhanced education condition consisted of a specially prepared slide-lecture show concerning kidney diseases and their treatment that was delivered by a trained research assistant. The standard education condition consisted of whatever educational procedures were routinely available at the participating hospital. All but six patients have now started treatment by maintenance dialysis. Individuals in the enhanced education condition survived an average of 4.6 months longer than did those in the standard education group without requiring the initiation of renal replacement therapy. This effect could not be attributed to physical differences between the groups, to cohort effects, to delays in contacting the patients, or to when or where they were identified. Possible mechanisms for this effect are discussed. PMID- 8501459 TI - Differences in illness intrusiveness across rheumatoid arthritis, end-stage renal disease, and multiple sclerosis. AB - Illness intrusiveness derives from illness-induced lifestyle disruptions that interfere with continued involvements in valued activities and interests and is hypothesized to represent a fundamental determinant of the psychosocial impact of chronic conditions. The present investigation compared reported levels of illness intrusiveness across 305 individuals from three chronically ill populations: rheumatoid arthritis (N = 110), end-stage renal disease (N = 101), and multiple sclerosis (N = 94). Although multiple sclerosis was significantly more intrusive, overall, into lifestyles, activities, and interests as compared with rheumatoid arthritis and end-stage renal disease (which did not differ), a significant illness group x life domain interaction indicated that intrusiveness into eight individual life domains differed significantly across the groups and that the pattern of differences varied as a function of the particular life domain involved. Differences in the constellations of signs, symptoms, and treatment regimens associated with a given condition were hypothesized to account for observed differences in illness intrusiveness. PMID- 8501460 TI - Information and psychopathology. AB - Our current understanding of mental processes in health and disease is limited by the absence of a practical model describing the physiology of the mind as an informational system. The mind is described here as a physical system with four functional dimensions that can be interrelated mathematically on the basis of information theory. These variables describe the information processing activities of the mind, and include: a) a state function (g), which is the number of potential states that the system can occupy at a given time and relates to the complexity and activity of the brain; b) a power function (P), the number of state changes per unit time; c) time (t); and d) the relative entropy of the system (R), which describes the ordering of mental states in time. Using these variables, the evolution of states of mind can be described as a trajectory in a multidimensional phase space representing all possible mental states. Ego functions constrain the field of brain states within this space, thereby giving rise to the information content of consciousness and to the individual psyche. Functional mental disorders, as disorders of the psyche, are dysfunctions in the ordering processes that give rise to conscious information. PMID- 8501461 TI - Emotional distress in disaster victims. A follow-up study. AB - One hundred thirteen adult victims of a major Latin American disaster were screened for emotional distress 1 and 5 years after the catastrophe. We used the Self-Reporting Questionnaire to identify emotionally distressed victims. Results indicate that the prevalence of emotional distress decreased from 65% in 1986 to 31% in 1990. However, a comparison of the symptomatology on these two assessments indicates a similarity in the frequency and profiles of symptoms among the distressed. Also, the most frequent symptoms and the strongest predictors of emotional distress were essentially the same. These findings provide empirical support to the clinically observed course of emotional symptomatology of disaster victims and to the focused training of health workers on selected emotional problems that are consistently present over time. PMID- 8501462 TI - Chronic delirium treated by daily dialysis in a patient suffering from chronic renal failure. PMID- 8501463 TI - Effects of various salts on the steady-state enzymatic activity of E. coli alkaline phosphatase. AB - Seventeen salts were tested at various concentrations for their effects on E. coli alkaline phosphatase steady-state activity. Three effects were distinguished: a general ionic strength effect, and weaker cation and anion effects. 1. All salts tested, including those with "noninteracting" cations and anions, stimulate alkaline phosphatase activity usually ca. 100% at moderate (0.05-0.3 M) concentrations. 2. Cations such as Na+ and Li+ produce further increases in activity at concentrations up to 1 M. The noninteracting cations tetramethylammonium and tetrapropylammonium produce lower activities at these concentrations. These do not provide the secondary stimulatory effect of cations such as Na+ or Li+. 3. Anions associated with greater "salting in" effectiveness such as thiocyanate also reduce activity at ca. 1 M concentrations. These latter effects are not dependent on protein concentration so they probably do not involve subunit dissociation. There is little effect on the fluorescence or fluorescence-polarization spectrum of the enzyme so there is no general effect of 1 M salts on the conformation of the protein. The Michaelis constant for the substrate, p-nitrophenylphosphate, and inhibition constant for inorganic phosphate are increased to some extent by salts, but the increase in activity is due to an increase in Vmax. Our working hypothesis is that increased ionic strength weakens electrostatic interactions, enabling noncovalently bound phosphate to dissociate more rapidly. PMID- 8501464 TI - NMR relaxation studies of the interaction of thiocyanate with lactoperoxidase. AB - The interaction of lactoperoxidase, LPO, with its substrate, thiocyanate, SCN-, has been investigated by 13C and 15N NMR relaxation measurements. When 0.1 M SCN , enriched with either 13C or 15N, was titrated with native ferric lactoperoxidase a large change in the spin-lattice relaxation time of the respective nucleus was observed. In the presence of saturating amounts of CN-, a high affinity ligand for the heme iron, a similar but much smaller change in the relaxation time for SCN- was found. Studies of the rate of carbon relaxation as a function of temperature have shown that thiocyanate is in fast exchange between a site on the enzyme and bulk solution. When LPO in either the absence or presence of CN- was titrated with SCN- a linear increase in the relaxation time was observed. Dissociation constants (Kd values) have been determined from a least squares analysis of these data. Apparent distances between the heme iron of lactoperoxidase and either the carbon or nitrogen atoms of bound thiocyanate ion have been determined through application of the Solomon-Bloembergen equation. These distances demonstrate that the observed association does not involve iron thiocyanate coordination, suggesting the possibility of an anion binding site. PMID- 8501465 TI - Binding of the ferric uptake regulation repressor protein (Fur) to Mn(II), Fe(II), Co(II), and Cu(II) ions as co-repressors: electronic absorption, equilibrium, and 57Fe Mossbauer studies. AB - The binding of the repressor protein (Fur) to Fe(II) as co-repressor was studied. Other transition metal ions such as Mn(II), Co(II), and Cu(II) were also studied as models. From the equilibrium studies Kd values of 55, 85, 36, and 10 microM were obtained for the Fur complex with Fe(II), Mn(II), Co(II), and Cu(II), respectively. The ratio of metal to Fur monomer was 1:1 in both the Fe(II) and Mn(II) complexes. Fur mutants were also studied. Electronic absorption spectra of the Co(II) Fur complex gave evidence of a distorted tetrahedral Co(II) site bound to sulfur. Frozen solution 57Fe Mossbauer spectra of the Fe(II) Fur indicated the presence of Fe(II) in a high spin distorted octahedral environment. The role of the metal ion as co-repressor in the binding of Fur to DNA is discussed in view of the above results. PMID- 8501466 TI - Psychosocial factors, alcohol use, and hangover signs among social drinkers: a reappraisal. AB - To reappraise a prior study of hangover signs and psychosocial factors among a sample of current drinkers, we excluded a subgroup termed Sobers, who report "never" being "tipsy, high or drunk." The non-sober current drinkers then formed the sample for this report (N = 1104). About 23% of this group reported no hangover signs regardless of their intake level or gender, and the rest showed no sex differences for any of 8 hangover signs reported. Using multiple regression, including ethanol, age and weight, it was found that psychosocial variables contributed independently in predicting to hangover for both men and women in this order: (1) guilt about drinking; (2) neuroticism; (3) angry or (4) depressed when high/drunk and (5) negative life events. For men only, ethanol intake was also significant; for women only, being younger and reporting first being high/drunk at a relatively earlier age were also predictors of the Hangover Sign Index (HSI). These multiple predictors accounted for 5-10 times more of the hangover variance than alcohol use alone: for men, R = 0.43, R2 = 19%; and for women, R = 0.46, R2 = 21%. The findings suggest that hangover signs are a function of age, sex, ethanol level and psychosocial factors. PMID- 8501467 TI - Bias, prevalence and kappa. AB - Since the introduction of Cohen's kappa as a chance-adjusted measure of agreement between two observers, several "paradoxes" in its interpretation have been pointed out. The difficulties occur because kappa not only measures agreement but is also affected in complex ways by the presence of bias between observers and by the distributions of data across the categories that are used ("prevalence"). In this paper, new indices that provide independent measures of bias and prevalence, as well as of observed agreement, are defined and a simple formula is derived that expresses kappa in terms of these three indices. When comparisons are made between agreement studies it can be misleading to report kappa values alone, and it is recommended that researchers also include quantitative indicators of bias and prevalence. PMID- 8501468 TI - The effect of using different reference dates for control exposure measurement on relative risk estimates in a case-control study. AB - In case-control studies in which case and control enrollment periods are not identical, exposure status for time-dependent variables is often measured relative to a reference date. Using data from a case-control study of the relation between cervical cancer and oral contraceptive (OC) use in which control enrollment began 6 months after the end of case enrollment, we evaluated the effect on odds ratios from using five different reference dates to determine the controls' exposure status. The choice of reference date had little effect on the odds ratios in this study. Reference dates for time-dependent exposure variables should be considered carefully in studies when case and control enrollment periods are not identical. PMID- 8501469 TI - Relative performance of the MAST, VAST, and CAGE versus DSM-III-R criteria for alcohol dependence. AB - A number of instruments have been developed to screen for alcoholism. With the advent of DSM-III and lay administered psychiatric diagnostic instruments, a test of the performance of these screens relative to diagnostic instruments is critical. In this paper, we document the relative effectiveness in a general medical clinic of the Michigan Alcoholism Screening Test (MAST), the Veterans Alcoholism Screening Test (VAST), and the CAGE questions in comparison to the DSM III-R criteria for alcohol dependence as measured in the Composite International Diagnostic Interview (CIDI). All of the screens performed at acceptable levels, but the MAST and VAST tended to have higher performance characteristics. At the recommended cut points, they had higher sensitivity for lifetime alcohol dependence (VAST 95.1%, MAST 90.2%, CAGE 78.0%) as well as higher specificity (VAST 80.3%, MAST 81.7%, CAGE 76.1%). For present alcohol dependence only, at the recommended cut points the MAST and CAGE had sensitivity of 100% but specificity of 62.0 and 61.0% respectively. The VAST had sensitivity of 83.3% and specificity of 89.0%. We conclude that all three perform well relative to DSM-III-R criteria. PMID- 8501470 TI - Factors predicting stage of breast cancer at diagnosis in middle aged and elderly women: the role of living arrangements. AB - We examined whether sociodemographic, health, and psychosocial factors predict stage at diagnosis in 444 women aged 55-84 with newly diagnosed, microscopically confirmed breast cancer. Stage was defined as local or advanced (regional or remote). One of the most interesting predictors of disease stage was living arrangement. The odds of being diagnosed with advanced disease were twice as great among women living with a spouse than among women living alone (95% CL = 1.16, 3.35), after adjusting for the effects of age, body mass index, income, comorbid conditions, smoking, and group membership. For those living with someone other than a spouse, the odds of advanced disease were 1.7 times greater than among those living alone (95% CL = 0.96, 3.06). Middle aged and older women who live alone may be more likely to monitor their own health and to use the health care system, and therefore have a greater chance of being diagnosed at an early stage of breast cancer. PMID- 8501471 TI - Effects on response rates and costs of stamps vs business reply in a mail survey of physicians. AB - In the general population, the use of stamps rather than business reply postage significantly improves response rates in mail surveys. Among physicians, however, a smaller effect might be anticipated due to their greater sophistication. An experiment was conducted to test the hypothesis that stamps would improve response rates and lower costs in a physician survey that included intensive follow up. In 1989, 380 physicians who reported providing primary care were surveyed. The protocol included two mailings, a postcard reminder, and two telephone reminders. Physicians were randomly assigned to receive a return envelope with a first-class stamp or an envelope that had been preprinted "business reply mail" in the first and second mailings. Response rates, calculated as completed surveys divided by eligible physicians, were 83.8 and 72.1% for stamps and business reply respectively, a difference of 11.7 percentage points (p < 0.01). Moreover, the total cost per completed survey was $11.18 for the physicians receiving stamps and $14.25 for the physicians receiving business reply. As in mail surveys of the general public, the use of first-class stamps on return envelopes both improves response rates and reduces cost in surveys of physicians. PMID- 8501472 TI - Validity of diagnoses of chronic diseases in general practice. The application of diagnostic criteria. AB - Certainty of a diagnosis is not only important for the patient but also for morbidity studies. In the absence of a gold standard, agreement with diagnostic criteria is often the best approach in measuring the certainty of a diagnosis. The agreement with diagnostic criteria has been studied for 5 chronic diseases (hypertension, chronic ischemic heart disease, diabetes mellitus, chronic nonspecific lung disease and osteoarthritis) in 7 general practices with a total practice population of 23,534 persons. Agreement with diagnostic criteria is operationalized into 3 categories. For each chronic disease a diagnostic quality measure per general practitioner is computed. Retrospective data have been collected in the practices on 2295 diseases in 1989 patients. Two-thirds of the diagnoses were made in general practice. The agreement with the diagnostic criteria for the cases diagnosed in general practice is high, ranging from 96% true positive cases in diabetes mellitus to 58% in chronic nonspecific lung disease. The highest rate of false positive cases is 4%. On the level of general practitioners diagnostic qualities vary from 62 to 96% true positive cases for the different diseases. The variation in diagnostic quality between general practitioners is substantial. The prevalence rates for the 5 chronic diseases are lower after adjustment by only including true positive cases. Diagnoses of the 5 chronic diseases recorded in general practice are generally valid with low numbers of false positive cases. PMID- 8501474 TI - Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35-49 years. AB - A total of 44,290 men and 24,535 women aged 35-49 have been followed with respect to different causes of death during 13.3 years on average. A detailed history of smoking, together with other important risk factors, were recorded in a standardized way. Compared with the classical American and British studies, the excess mortality for the smokers was largely the same for the majority of causes. The exceptions were cerebrovascular mortality and suicides and accidents, which were more strongly related to smoking in this study. Furthermore, men who smoked only pipe, had nearly the same coronary heart disease mortality as men who smoked only cigarettes. The same applies to lung cancer mortality. Among men who had quit cigarette smoking, the coronary heart disease mortality decreased with time since quitting to almost the level of the never cigarette smokers after 5 years or more. PMID- 8501473 TI - Comorbidity of chronic diseases in general practice. AB - With the increasing number of elderly people in The Netherlands the prevalence of chronic diseases will rise in the next decades. It is recognized in general practice that many older patients suffer from more than one chronic disease (comorbidity). The aim of this study is to describe the extent of comorbidity for the following diseases: hypertension, chronic ischemic heart disease, diabetes mellitus, chronic nonspecific lung disease, osteoarthritis. In a general practice population of 23,534 persons, 1989 patients have been identified with one or more chronic diseases. Only diseases in agreement with diagnostic criteria were included. In persons of 65 and older 23% suffer from one or more of the chronic diseases under study. Within this group 15% suffer from more than one of the chronic diseases. Osteoarthritis and diabetes mellitus are the diseases with the highest rate of comorbidity. Comorbidity restricts the external validity of results from single-disease intervention studies and complicates the organization of care. PMID- 8501475 TI - Quandaries. PMID- 8501476 TI - Design of a prospective study of the pulmonary complications of human immunodeficiency virus infection. The Pulmonary Complications of HIV Infection Study Group. AB - Because no studies have systematically described the pulmonary complications associated with early stages of infection with the human immunodeficiency virus (HIV), the National Heart, Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases jointly initiated a prospective cohort study in 1987 to describe the incidence and course of lung diseases at all stages of HIV infection. This paper describes the ongoing study and highlights some of its unusual features. Six clinical centers from different geographic areas in the U.S. began enrolling participants in 1988, and the resulting cohort comprises 1353 members. HIV seropositive participants were randomized to "intensive" (pulmonary disease screening and follow-up at 3-month intervals) or "routine" (6 month follow-up intervals with annual screening) follow-up to assess the impact of these strategies on patient outcomes. New information from this complex study will lead to a broader understanding of the pulmonary diseases associated with HIV infection and will have relevance to clinical as well as epidemiologic aspects of HIV disease. PMID- 8501477 TI - A randomized trial about the perceived informativeness of new empirical evidence. Does beta-carotene prevent (cervical) cancer? AB - The perceived informativeness of a publication can be assessed by measuring the change in belief it induces among the scientific public, regarding a certain hypothesis. In a randomized trial, we studied the effect of empirical evidence from a clinical experiment and a case-control study on the hypothesis that beta carotene protects against (cervical) cancer. The study population consisted of first authors of recently published patient-oriented research papers. They received an abstract of the clinical experiment, of the case-control study, or a "placebo" abstract. The latter was used to assess the specific effect of the empirical evidence in the two real studies. The change in belief in the hypotheses was expressed as a likelihood ratio (LR). All three abstracts led to a decrease in belief in the hypothesis. The median LRs of the abstracts of the experiment, case-control study and "placebo" were 0.33, 0.45, 0.75 respectively. This paper shows that the belief in a certain hypothesis is influenced by the quality of empirical evidence in a study. The magnitude of change induced by the experimental and case-control abstract had the anticipated order, but the change in belief induced by the "placebo" abstract was larger than we had expected. Reasons for this may be the concise information in the abstract and the variable methodological training of the study population. PMID- 8501478 TI - Widowhood and mortality risk in a community sample of the elderly: a prospective study. AB - Mortality risk during early bereavement was examined in a community sample of 1046 married elderly persons 65 years and over, followed from 1982 to 1988. Cox' regression models with time-dependent covariates were computed to estimate mortality risk, while controlling for pre-widowhood sociodemographic and health related variables. Elderly young-old (65-74) and old-old men (> or = 75) showed slightly elevated age-adjusted relative risks (RR) during the first 6 months of widowhood (RR = 1.69; 95% CI: 0.86-3.31 and RR = 1.79; 95% CI: 0.44-7.28 respectively). These RRs increased slightly after adjustment for pre-widowhood control variables. The age-adjusted RR during early widowhood for young-old women was 2.87 (% CI: 0.81-2.42), which increased to 3.86 (95% CI: 1.11-13.45) after adjustment for sociodemographic and health-related variables. This analysis stresses the usefulness of Cox' regression models with time-dependent covariates to calculate mortality risk for variable periods after onset of widowhood adjusted for pre-widowhood characteristics. However, the power of the study was limited, resulting in mostly insignificant risk estimates and wide confidence intervals. PMID- 8501479 TI - Interviewer versus self-administered questionnaires in developing a disease specific, health-related quality of life instrument for asthma. AB - We wished to determine the extent to which respondents provided the same answers to a health-related quality of life (HRQL) questionnaire in self- and interviewer administered forms. One hundred and fifty patients with asthma who were symptomatic or required treatment at least once a week, and had airway hyperresponsiveness to methacholine aerosol (PC20 < 8.0 mg/ml) participated. Patients completed a 152-item HRQL questionnaire in both interviewer and self administered forms, separated by a 2-week interval, the order determined by random allocation. The percentage of items endorsed by the self-administered approach was significantly higher than that of the interviewer-administered approach overall (46.9 vs 35.8%) (p < 0.0001). The difference was consistent across all six domains; the absolute difference in the proportion of items endorsed varied from 8.9 to 12.3%. The intraclass correlations for the proportion of subjects endorsing an item was 0.84. Self- and interviewer-administered questionnaires yield very similar results in discriminating between subjects, but the self-administered version shows systematically greater HRQL impairment. PMID- 8501480 TI - Socioeconomic and demographic factors that predict where children receive cancer care in Florida. AB - Socioeconomic and demographic factors associated with type of facility (cancer center vs non-cancer center) at which a child with cancer is seen were identified to suggest interventions to increase access to state-of-the-art care. The 2268 children with cancer in Florida (1981-1986) were classified as ever having been seen or not having been seen at a cancer center. Patients referred from one type of facility to another were compared to those not referred. Nineteen percent of children with cancer were never seen at a cancer center. These children were likely to be older (15-19 years of age), have Hodgkin's disease or a brain tumor, reside in a county without a cancer center, or have higher median income. Interventions extending state-of-the-art cancer care beyond cancer centers should target (1) physicians treating adolescent-aged children and (2) patients for whom private insurance may serve as a barrier to referral and protocol therapy. PMID- 8501481 TI - Selection bias from differential residential mobility as an explanation for associations of wire codes with childhood cancer. AB - Several studies of childhood cancer, especially leukemia, in residential areas have reported an association with wire configuration codes. These codes were suggested to be surrogates of electromagnetic field exposure. However, the selection criteria used in several of the studies caused the case and control populations to be non-comparable, especially with respect to residential mobility. Specifically, controls were required to be residentially stable but cases were not. Thus, an artificial association between residential mobility and cancer was created by the subject selection procedure. The present study of 5721 residences in Columbus, Ohio was conducted to learn if bias due to differences in residential mobility, rather than electromagnetic fields, could explain the reported association between wire configuration codes and childhood cancer. It was found that the proportion of homes classified as "high" wire code in the non stable population was 31% greater than the corresponding proportion in the stable population. This finding shows that high wire codes are associated with homes in which the residents are mobile and low wire codes are associated with homes occupied by stable residents. Thus, as a consequence of this association between residential mobility and high wire codes, studies that created an artificial association between residential mobility and childhood cancer will also produce a false association between high wire codes and cancer. PMID- 8501482 TI - Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. AB - The relationship between disability and various musculoskeletal disorders was investigated in 7217 men and women representative of the Finnish population aged 30 years or more. They participated in the Mini-Finland Health Survey and were first screened by interview and questionnaire about limitations in daily activities. The outcome variables were reduced working capacity, an occasional need for assistance in daily activities, and a regular need for assistance in daily activities. In a two-phase medical examination, all cases fulfilling predetermined diagnostic criteria of musculoskeletal, cardiovascular, respiratory and mental disorders and diabetes were recorded independently. In multivariate logistic regression analyses, inflammatory arthritis was the strongest determinant of all forms of disability. Osteoarthritis, especially in the hip, was a strong determinant of both occasional and regular need for assistance, and chronic low back pain was a strong determinant of reduced working capacity and occasional need for assistance among those aged 30-64 years. Other musculoskeletal disorders also determined the prevalence disability, but these relationships were reduced by taking comorbidity into account. A low level of education and a low (less than 20 kg/m2) or very high (at least 35 kg/m2) body mass index represented independent determinants of all forms of disability, and a history of physically strenuous work an independent determinant of reduced working capacity, when disabling illness was adjusted for. The proportion of all forms of disability attributable to musculoskeletal disorders, in models including, age, sex, other disabling illness and significant non-medical determinants of disability, was close to 20%. The disorders with the highest community impact were chronic low back pain among those aged 30-64, osteoarthritis of the hips and knees and inflammatory arthritis. PMID- 8501483 TI - Validity of cardiovascular disease risk factors assessed by telephone survey: the Behavioral Risk Factor Survey. AB - The Behavioral Risk Factor Surveillance System (BRFSS) collects telephone interview data on behaviors for the leading causes of premature death and disability. Its validity has never been adequately studied. The authors replicated BRFSS methodology to validate self-reported cardiovascular disease (CVD) risk factors. Nine-hundred and eleven subjects from three upstate New York counties were interviewed between 1/89 and 5/90. Interviewees were offered physical examinations and laboratory testing for CVD risk factors; 282 men and 344 women participated. The authors studied validity by comparing objectively measured to self-reported CVD risk factors. Sensitivities for self-reported hypertension, hypercholesterolemia, obesity, smoking, and diabetes were: 43, 44, 74, 82 and 75%, respectively. Only smoking sensitivity differed by gender: men, 77%; women, 86%. Specificity was > 85% for all risk factors, except hypercholesterolemia in men (75%). Prevalence was underreported for hypertension, hypercholesterolemia, obesity, and smoking by 43, 50, 25 and 17%, respectively. Results suggest telephone survey research includes physiologic measurements for blood pressure, cholesterol, height, weight, and smoking to validate self reported CVD risk factors. When this is impossible, results such as these can be used, in similar samples, to correct risk factor prevalence rates from telephone surveys for misclassifications. PMID- 8501484 TI - Long-term mortality of Nazi concentration camp survivors. AB - Nazi concentration camp survivors have been shown to have excess mortality in the first 20 years following their release. To determine if this excess persists, Israeli civil servants were studied. Mortality of camp survivors and of other post-war European immigrants was compared 20-41 years following World War II. Using survival analysis and proportional hazards models, no difference in mortality rates was found. PMID- 8501485 TI - Clinical reasoning and the new "non-" nosology. AB - Although seemingly odd, the designations prefixed with "non-" have become a familiar feature of clinical terminology. A common structure of these designations is the partition of a single clinical category into two contrasting ones. Despite the similar "non-" designations, the partitions can have four different functions: dividing one disease into two, aggregating multiple diseases, distinguishing etiologic uncertainty, and negating "legitimate" disease. The "non-" terminology may seem peculiar, but it is based on clinically pertinent distinctions and similarities in disease, reflecting prudent clinical reasoning. PMID- 8501486 TI - Use of prescription and non-prescription drugs in pregnancy. The Baltimore Washington Infant Study Group. AB - We analyzed use of therapeutic drugs during pregnancy by 2752 mothers of infants without major congenital malformations. During pregnancy, 68% of the women used at least one prescription or non-prescription drug. Drug use in pregnancy was significantly more common for women who were white, older, married, better educated, of higher income and occupational status, receiving private prenatal care and not living in urban areas. Number of maternal illnesses, higher socioeconomic status, white race, multiparity and use of recreational drugs explained 26% of reported drug use. The mean number of drugs reported (1.2) underestimates total drug exposure due to exclusion of some drug categories including multivitamins and illicit drugs. Since the majority of women giving birth to normal infants report use of at least one pharmacologic agent during pregnancy, attribution of adverse outcome to drug use in an individual case is rarely justified. PMID- 8501487 TI - The physician as the patient's advocate. American Society of Clinical Oncology Committee of Patient Advocacy. PMID- 8501488 TI - Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group. AB - PURPOSE: We analyzed the long-term results of a Childrens Cancer Group (CCG) randomized study comparing cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) versus LSA2L2 as treatment for childhood non-Hodgkin's lymphoma. The initial results were previously reported (N Engl J Med 308:559, 1983). PATIENTS AND METHODS: A total of 429 patients are reported here, 68 with localized disease and 361 with disseminated disease. The distribution of disseminated-disease patients by histologic type was 164 lymphoblastic, 60 large cell, and 137 undifferentiated lymphomas. Median follow-up duration of surviving patients is 8 years. RESULTS: Event-free survival (EFS) of patients with localized disease was 84% at 5 years. No differences were seen between the two treatment regimens. Results for patients with disseminated disease was dependent on histologic subtype: patients with lymphoblastic lymphoma did better when treated with LSA2L2 (5-year EFS of 64% v 35% for COMP); COMP produced better results for patients with undifferentiated lymphoma (5-year EFS of 50% v 29% for LSA2L2). Results for large-cell lymphoma patients were similar (5-year EFS of 52% for COMP v 43% for LSA2L2). Five percent of patients died of treatment-related complications while on therapy (primarily infections). Only four deaths without progression have been observed off-therapy (two from restrictive lung disease, one from an acute asthma attack, one from colon cancer). Patient survival rates after recurrence were poor. CONCLUSION: Treatment success can be expected in 84% of pediatric patients with localized non-Hodgkin's lymphoma. For patients with disseminated disease, treatment success can be expected in 64% of those with lymphoblastic and 50% of those with undifferentiated or large-cell disease. To date, late adverse events are rare. PMID- 8501489 TI - Cardiac dysfunction following spinal irradiation during childhood. AB - PURPOSE: Although spinal irradiation used in the treatment of CNS malignancies includes a portion of the heart in the radiation field, cardiac effects have not been previously reported. PATIENTS AND METHODS: We compared patients treated for malignancy in childhood with spinal irradiation (n = 26) with patients treated with mediastinal/flank irradiation (n = 47) that included the heart in the radiation field. All patients were more than 1 year from completion of radiation therapy. Patients underwent at least two of the following cardiac evaluations: (1) ECG; (2) 24-hour ambulatory ECG; (3) echocardiogram; and (4) exercise-testing using cycle ergometry. RESULTS: Twelve of 16 patients (75%) in the spinal irradiation group with an assessable exercise test achieved a maximal cardiac index (MCI) below the fifth percentile as compared with 13 of 40 patients (32%) who had received mediastinal/flank irradiation (P = .007). Furthermore, after adjusting for normal heart growth, radiation and anthracycline doses, and follow up time, the group of patients who received spinal irradiation had significantly higher estimated posterior wall stress (P = .002), expressed as the natural logarithm of the ratio of end-diastolic left ventricular internal diameter (LVID) to left ventricular posterior wall thickness (LVPWT), than the group who had received mediastinal/flank irradiation. Finally, eight of 26 patients (31%) in the spinal group had pathologic Q-waves in the inferior leads versus three of 47 (6.4%) in the mediastinal/flank group (P = .001). CONCLUSION: Patients who have received spinal irradiation for pediatric malignancies appear to be at risk for significant cardiac dysfunction. The asymmetric distribution of radiation to a growing heart, as given with spinal irradiation, may be the cause of these findings. PMID- 8501490 TI - Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group. AB - PURPOSE: This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS: From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS: Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION: The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission. PMID- 8501491 TI - Effect of prior interferon alfa therapy on the outcome of allogeneic bone marrow transplantation for chronic myelogenous leukemia. AB - PURPOSE: To determine whether prior interferon alfa (IFN-A) treatment affects the outcome of allogeneic bone marrow transplantation. PATIENTS AND METHODS: We analyzed the outcome of 77 patients with chronic myelogenous leukemia (CML) who received transplants from an HLA-identical donor using a total-body irradiation containing preparative regimen. Engraftment, acute and chronic graft-versus-host disease (GVHD), survival, and disease-free survival were compared between patients who had previously received interferon (IFN+) to those who had not (IFN ). Forty-one patients were transplanted in chronic phase and 36 had more advanced CML. The IFN+ group had received IFN-A in doses of 3 to 5 x 10(6) U/m2 three times a week or more for at least 4 weeks anytime before transplantation. RESULTS: For patients in chronic phase, there were no significant differences between the IFN+ group and the IFN- group in regard to neutrophils recovery more than 1.0 x 10(9)/L (29 v 24), platelet recovery more than 50 x 10(9)/L (33 v 36), incidence of grade II to IV GVHD (23% v 28%), incidence of chronic GVHD (39% v 47%), disease-free survival (46% +/- 11% v 59% +/- 13%), relapse (9% v 11%), or 100-day transplant-related mortality (22% v 16%). In patients with more advanced stage disease, there was also no significant differences between the IFN+ group and the IFN- group in regard to these outcomes. CONCLUSION: Prior treatment with IFN-A did not adversely affect transplant outcome. Further studies are required to better understand the complementary roles of IFN-A and allogeneic bone marrow transplantation for the treatment of CML. PMID- 8501492 TI - Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease. AB - PURPOSE: To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS: Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS: Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). CONCLUSION: Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy. PMID- 8501493 TI - Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma: evidence for a schedule-dependent effect favoring infusional administration of chemotherapy. AB - PURPOSE: This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. PATIENTS AND METHODS: Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C, most (81%) had received D, and a minority (16%) had received E. RESULTS: Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10+ to 38+), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38+). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9+ to 24+). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group. CONCLUSION: Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor prognosis NHL when used as initial therapy, and merits further study in that setting. PMID- 8501494 TI - Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin's disease. AB - PURPOSE: We report an unexpectedly high incidence of hypersensitivity to etoposide among 45 patients with newly diagnosed Hodgkin's disease treated with vinblastine, etoposide, prednisone, and doxorubicin (VEPA) plus radiation. PATIENTS AND METHODS: Twenty-three of 45 patients (51%) had one or more acute hypersensitivity reactions to etoposide administration. The 23 patients were 8 to 18 years of age (median, 15 years); 12 were males. Four patients had experienced prior allergic reactions to antibiotics or intravenous contrast media. RESULTS: Hypersensitivity reactions followed the first or second dose of VEPA in most cases. The reactions occurred at a median time of 5 minutes (range, 3 to 120) from the start of the etoposide infusion. Fifteen patients reacted early (within 10 minutes), four midway through the infusion, and four after completion of the infusion. Signs and symptoms included flushing, respiratory problems, changes in blood pressure, and abdominal pain with or without nausea and vomiting. Respiratory problems included dyspnea, chest pain/tightness, bronchospasm, and cyanosis. Symptoms were alleviated by discontinuing the etoposide infusions and administering diphenhydramine and/or hydrocortisone; epinephrine was required to reverse bronchospasm in three cases. All 23 patients recovered without adverse sequelae and were rechallenged with etoposide. Fifteen patients tolerated subsequent etoposide infused at a slower rate, with antihistamine and/or corticosteroid premedication; five had recurrent hypersensitivity despite these measures. Three of these five developed similar symptoms when teniposide was substituted for etoposide. Three patients who had isolated episodes of hypotension on completion of the etoposide infusion successfully received subsequent infusions without premedication or change in infusion rate or concentration. CONCLUSION: Despite this unexpectedly high incidence of hypersensitivity among Hodgkin's disease patients treated with etoposide, rechallenge with the drug was successful in 78% of cases. PMID- 8501495 TI - Gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy. AB - PURPOSE: To determine the predictive value of gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality treatment. PATIENTS AND METHODS: A retrospective study was performed of 48 patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality therapy. Patients were monitored with whole-body planar scans (34 patients) or chest single-photon-emission computed tomography (SPECT) plus planar abdominal imaging studies (14 patients). Scans were performed at diagnosis, following three to eight cycles of chemotherapy, and after the end of treatment. The value of gallium scans in modifying treatment and predicting outcome was assessed. RESULTS: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum. After chemotherapy, four patients had residual mediastinal activity; two patients with persistent activity on planar scans failed to enter remission and died of disease; two other patients with abnormal activity only seen on SPECT had therapy modified and remain in remission. After chemotherapy, 44 patients had a normal gallium scan. Twelve patients with negative scans relapsed, including nine patients with recurrence above the diaphragm. CONCLUSION: The use of gallium scans after several courses of chemotherapy resulted in a modification of treatment in four patients, including two patients who are apparently cured. However, after negative scans, 20% of patients relapsed above the diaphragm. These results suggest that gallium imaging, including SPECT, is of limited value in predicting disease sterilization, although the number of patients studied with SPECT was small. At present, the major value of gallium scans is to identify patients who may benefit from a modification of treatment. PMID- 8501496 TI - Prognostic role of serum beta 2-microglobulin in Hodgkin's disease. AB - PURPOSE: To evaluate the role of serum beta 2-microglobulin (beta 2M) in the prognosis of patients with Hodgkin's disease. PATIENTS AND METHODS: One hundred sixty previously untreated patients with Hodgkin's disease had serum beta 2M levels determined before initiation of treatment. Serum beta 2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including beta 2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed. RESULTS: Serum beta 2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum beta 2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease. CONCLUSION: Serum beta 2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis. PMID- 8501497 TI - Postoperative radiation therapy for high-risk colon carcinoma. AB - PURPOSE: This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies. PATIENTS AND METHODS: From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only. RESULTS: Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy. CONCLUSION: Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection. PMID- 8501498 TI - Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report. AB - PURPOSE: In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS: Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS: Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION: The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery. PMID- 8501499 TI - A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. AB - PURPOSE: To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer. PATIENTS AND METHODS: One hundred sixty two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry. RESULTS: Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups. CONCLUSION: It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day. PMID- 8501500 TI - High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. AB - PURPOSE: We studied high-dose cyclophosphamide, cisplatin, and carmustine (CPA/cDDP/BCNU) with autologous bone marrow support (ABMS) as consolidation after standard-dose adjuvant chemotherapy treatment of primary breast cancer involving 10 or more axillary lymph nodes. PATIENTS AND METHODS: One hundred two women with stage IIA, IIB, IIIA, or IIIB breast cancer involving 10 or more lymph nodes at surgery were registered; 85 were eligible, treated, and assessable. Patients were treated with four cycles of standard-dose cyclophosphamide, doxorubicin, and fluorouracil (CAF), followed by high-dose CPA/cDDP/BCNU with ABMS. RESULTS: Actuarial event-free survival for the study patients at a median follow-up of 2.5 years is 72% (95% confidence interval, 56% to 82%). Comparison to three historical or concurrent Cancer and Leukemia Group B (CALGB) adjuvant chemotherapy trials selected for similar patients showed event-free survival at 2.5 years to be between 38% and 52%. Therapy-related mortality was 12%; pulmonary toxicity of variable severity occurred in 31% of patients. Quality-of-life evaluations indicate that patients are functioning well without major impairments. CONCLUSION: High-dose consolidation with CPA/cDDP/BCNU and ABMS after standard-dose CAF results in a decreased frequency of relapse in patients with high-risk primary breast cancer compared with historical series at the median follow-up of 2.5 years. Evaluation in a prospective, randomized trial is warranted and currently underway. PMID- 8501501 TI - Cell kinetics as a predictive factor in node-positive breast cancer treated with adjuvant hormone therapy. AB - PURPOSE: The fraction of cells that incorporate 3H-thymidine (3H-dT labeling index [3H-dT LI]) proved to be a prognostic indicator in patients with node negative and node-positive resectable breast cancers treated with locoregional treatment alone or with adjuvant combination chemotherapy. In this study, we assessed the prognostic role of 3H-dT LI alone and in association with other pathologic and biologic variables in a series of 249 women with node-positive breast cancers treated with adjuvant endocrine therapy. PATIENTS AND METHODS: All patients were postmenopausal, had resectable estrogen receptor-positive (ER+) tumors, and had received tamoxifen for at least 1 year after radical or conservative surgery plus radiotherapy. The median follow-up duration was 48 months. RESULTS: The 4-year relapse-free survival (RFS) rates were significantly lower for patients with large tumors (> 2 cm), with more than three positive lymph nodes, with low (< 150 fmol/mg proteins) ER content, without progesterone receptors (PgRs), or with rapidly proliferating tumors. 3H-dT LI provided prognostic information independent of axillary node involvement, ER content, PgR status, and tumor size, with an estimated odds ratio (OR) higher than that of tumor size, lymph node involvement, or ER concentration. In addition, 3H-dT LI and PgR in association were able to identify patients with different risks of relapse within subsets of tumors with less or more than three positive nodes. CONCLUSION: 3H-dT LI provides prognostic information complementary to PgR, tumor size, lymph node involvement, and ER content in the prediction of RFS of postmenopausal patients with node-positive, ER + resectable tumors treated with adjuvant hormone therapy. PMID- 8501502 TI - Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer. AB - PURPOSE: To determine (1) the impact of cyclophosphamide 600 mg/m2 on previously defined relationships between carboplatin area under the plasma concentration versus time curve (AUC) and indices of toxicity and response in women with advanced ovarian cancer; and (2) the relationships between indices of cumulative drug exposure and clinical outcomes. METHODS: Carboplatin AUC = dose/(creatinine clearance [CCr] + 25) and was calculated in 224 women who received carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2. The likelihood of grade 3 or greater myelotoxicity at any carboplatin AUC was compared with the likelihood of myelotoxicity at the same single-agent carboplatin AUC. The nadir count predicted using the University of Maryland single-agent carboplatin dosing formula was compared with the nadir count observed. Received and relative-received dose intensity were calculated. Carboplatin exposure-intensity was defined by substituting cumulative carboplatin exposure for total dose. Relationships were sought between these indices and therapeutic outcomes. RESULTS: The incidence of leukopenia and thrombocytopenia at any carboplatin AUC was greater for the two drug combination than for single-agent carboplatin. The platelet nadir in 83% of patients was less than or equal to the nadir predicted for the same single-agent carboplatin AUC. Despite a narrow range of received dose-intensities, carboplatin exposure-intensity was distributed over a twofold range. There were no relationships between received and relative-received dose-intensity or carboplatin exposure-intensity and time to progression or survival. CONCLUSION: Any carboplatin AUC when administered with cyclophosphamide 600 mg/m2 produces greater myelotoxicity than the same AUC of single-agent carboplatin. Received carboplatin dose-intensity underestimates the range of plasma drug exposure resulting from a fixed carboplatin dosing regimen. Whether higher carboplatin exposures can improve outcome requires prospective validation. PMID- 8501503 TI - Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients. AB - PURPOSE: To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS: From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS: Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION: These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy. PMID- 8501504 TI - Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. AB - PURPOSE: We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy. RESULTS: Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2 , and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years. CONCLUSION: Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment. PMID- 8501505 TI - Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring. AB - PURPOSE: Recent innovations allow the integration of microelectronics into drug packaging, providing a continuous record of the interactions of the patient with the drug package. We hypothesized that adherence to oral tamoxifen, as measured by a pressure-activated microelectronic monitoring device, would be significantly discrepant from traditional measures of patient adherence, ie, patient self report (SR) and pill counts (PCs). PATIENTS AND METHODS: Twenty-six patients receiving oral tamoxifen therapy were assessed by patient SR, PCs, and Medication Event Monitoring System (MEMS; Aprex Corp, Fremont, CA) microelectronic monitoring. A microprocessor in the MEMS cap recorded each opening as a presumptive dose, listing the date, time, and duration of opening for later retrieval on a microcomputer. Patients were not informed that their adherence was to be monitored electronically or that PCs would be performed. RESULTS: A total of 2,102 days (70.1 months) of tamoxifen therapy were monitored; patients were monitored for a mean of 2.92 months of tamoxifen therapy. SR adherence to oral tamoxifen was significantly higher than that suggested by either PCs (SR missed doses only v PC, P = .008) or MEMS adherence monitoring (SR missed doses only v MEMS missed doses only, P = .005; SR dosing-interval errors only v MEMS dosing interval errors only, P < .0001; SR all dosing errors v MEMS all dosing errors, P < .0005). PC data also suggested significantly higher adherence rates than MEMS monitoring. CONCLUSION: Microelectronic adherence monitoring provides both confirmatory and complimentary data regarding adherence behavior, while also allowing for the evaluation of patterns of nonadherence. Patient SRs and PCs likely overestimate the degree to which patients adhere to their tamoxifen regimen. PMID- 8501506 TI - Cancer pain or "total" cancer pain? PMID- 8501507 TI - Peptides and the primary afferent nociceptor. AB - An expanding knowledge of neuropeptides and their function has led to a profound change in our view of how the PAN contributes to pain. In addition to their expected direct action on postsynaptic cells in the dorsal horn, neuropeptides can modify transmitter release from nearby terminals of other PANs and/or diffuse to act on dorsal horn neurons at a considerable distance from their site of release (Fig. 2). Contrary to early expectations and despite the evidence that several neuropeptides excite central nociceptive neurons, there is no clear correspondence between neuropeptide content and physiologically defined classes of small-diameter primary afferents. There is, however, a tendency for populations of afferents innervating different organs to differ consistently in their peptide content. In fact, the peptide content of primary afferents is, in part, determined by specific factors in the tissues that they innervate. Furthermore, peptide content can change dramatically in response to certain prolonged stimuli or nerve damage. The lack of correspondence of peptide content and physiological response pattern, the plasticity of peptide content, its tissue specificity, and the possibility for action at a distance from the site of their release from central PAN terminals strongly suggest that PAN peptides have functions that are fundamentally different from those of the short-range actions of amino acid neurotransmitters that are also found in the PAN. Finally, nowhere is the plasticity of function of the PAN more evident than at its peripheral terminals. Long-term changes are produced in these terminals by a host of peptides that derive from a variety of cell types. The complexity of this transduction process is augmented by the activity-induced release of peripherally active neuropeptides from the PAN itself. In addition to the variety of fundamental neurobiological issues that recent studies of PANs have raised, they have also generated a great deal of clinical interest, in view of the role of the PAN in inflammation and its accessibility for study and for therapeutic intervention. PMID- 8501508 TI - Response dynamics and directional properties of nonspiking local interneurons in the cockroach cercal system. AB - The response properties and directional receptive fields of nonspiking local interneurons in the cercal system of the cockroach are described. Wind-evoked responses were recorded intracellularly, and then analyzed by means of the Wiener kernel method in which a Gaussian white noise signal was used as a stimulus. Cross-correlation between the response and the white noise signal produced first- (linear) and second-order (nonlinear) kernels that were used to define input output characteristics of the interneurons. Three sets of interneurons were distinguished on the basis of kernel analysis. First, responses in interneurons 101, 107, 111, and 203 were characterized predominantly by a differentiating first-order kernel, which suggests a linear relationship to the stimulus. The amplitude and waveform of the kernel changed with the change in stimulus angle, indicating that these four cells are directionally sensitive. Second, responses in interneurons 102 and 103 were also directionally sensitive but highly nonlinear. The first-order kernel was biphasic, whereas the second-order kernel had an elongated depolarizing peak on the diagonal. The response dynamics were accounted for by a cascade of two filters, a linear band-pass filter and a static nonlinear filter, in which the nonlinearity is a signal compression (or a rectification). Third, responses in interneurons 104 and 201 consist largely of the second-order nonlinear component. The second-order kernel, which had an elongated depolarizing peak or a hyperpolarizing valley on the diagonal, did not show any directional preference. The second-order nonlinearity was dynamic, and could be modeled by a band-pass linear filter-static nonlinearity-low-pass linear filter cascade, where the static nonlinearity is a full-wave rectification. The band-pass filter would simply reflect the mechanical property of cercal hair sensilla, whereas the low-pass filter represents the transfer at synapses between the cercal afferents and the interneurons. The nonlinear response thus explains the difference in the directional sensitivity while the differentiating first order kernel explains the velocity sensitivity of the interneurons. We show that 101 and 107 respond most preferentially to wind from the left versus right, whereas 102, 103, 111, and 203 respond to wind from the front versus rear. Thus, it is suggested that there are two subsystems responding maximally to wind displacement along two coordinate directions, one for the longitudinal direction and the other for the transverse direction. On the other hand, the full-wave rectifier nonlinear interneurons are omnidirectional, and thus suggested to code simply the power of the wind displacement. PMID- 8501509 TI - Neural computations for sound pattern recognition: evidence for summation of an array of frequency filters in an echolocating bat. AB - Microchiropteran bats use an auditory sonar system for orientation and prey capture. Many bats use highly structured constant-frequency (CF) and frequency modulated (FM) sonar orientation signals. Mechanisms for sound pattern recognition are important for the perception of these and other types of auditory signals. The processing and recognition of FM sound components appears to be important for certain complex perceptual tasks, including target distance perception. I have conducted behavioral studies using artificial echoes to simulate the conditions of a bat flying toward a target. An innate vocalization response of the bat to the simulated approaching target was used to assess the ability of the bat to analyze the structure of and extract distance information from different types of synthetic FM sound patterns. The bat's performance depended on the structure of the artificial echo. The pattern recognition performance of the bats was similar when they were presented with either a naturally structured artificial CF/FM echo or an artificial CF/FM echo containing an FM component consisting of a series of pure tone steps. The ability of the bats to recognize appropriately the structure of an FM signal constructed from a sequence of pure tones depended on the number of pure tone steps in the series. Noctilio was able to recognize FM sound patterns containing 99 or greater pure tone steps. The minimum required number of pure tone steps could be distributed over different frequency ranges. The bats were able to resolve individual tone steps in the series that were separated by at least 100 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501510 TI - Calcium-induced translocation of synaptic vesicles to the active site. AB - The effect of increasing [Ca2+]o on the positioning of synaptic vesicles relative to the active site in resting coxal neuromuscular junctions of Drosophila was investigated. In normal saline (1.8 mM Ca2+) only a very small percentage of sites possess a vesicle docked under the dense body plate close to the plasma membrane in a readily releasable position. However, after exposure to elevated Ca2+ salines (3.6, 9, 18 mM), an increase in the number of active sites possessing docked vesicles was observed. Also, an increase in the average number of docked vesicles/site was seen. Intracellular recordings from coxal muscle fibers in normal saline and elevated Ca2+ salines were made, and it was observed that exposure to elevated Ca2+ saline caused an increase in miniature excitatory junction potential (mejp) frequency and in multiquantal and clustered mejps. Thus, when the number of active sites possessing docked vesicles increases, the frequency of spontaneous release also increases. Furthermore, when the number of docked vesicles/site increases, the number of multiquantal mejps increases. The data suggest that Ca2+ may be involved in vesicle translocation to the active site, and that the concentration of Ca2+ in the terminal may regulate the number of active sites that possess readily releasable vesicles. The effects of increasing the number of docked vesicles on spontaneous release characteristics are discussed. PMID- 8501511 TI - Texture perception and afferent coding distorted by cooling the human ulnar nerve. AB - The roughness of standardized surfaces (embossed dot arrays or gratings) was compared by scanning them with the little finger of either hand while the ulnar nerve was cooled unilaterally at the elbow; both hands remained warm. Across-hand comparison of roughness showed that a given surface felt smoother on the cooled side. When the surfaces were adjusted to feel equally rough, that on the cooled side would normally have felt appreciably rougher. The effect of the nerve cooling on axonal conduction was monitored during the psychophysical experiments by stimulating the ulnar nerve above the cooled region and recording the EMG of an ulnar-innervated hand muscle. During cooling, large myelinated axons remained unblocked, but prolongation of their absolute refractory period to 5-10 msec left them unable to transmit trains of impulses at high frequencies (Wedensky inhibition). By varying the length of nerve cooled and the cooling temperature, it was shown that the perceptual effects were not due to an increase in the normal temporal dispersion of impulses transmitted by different-sized afferents. The effect of increasing the absolute refractory period on the signals from the various types of cutaneous afferent was modeled mathematically, using earlier human single-fiber responses to dot arrays. It is concluded that the reduction of perceived roughness with nerve cooling is due to Wedensky inhibition, and that the percept of roughness is related to the local contrast in the afferent spatiotemporal image. PMID- 8501512 TI - Hyperactivity and sensitization to psychostimulants following cholera toxin infusion into the nucleus accumbens. AB - Although manipulation of second messenger systems is widespread in cell biology, there are few experiments examining the consequences of such manipulation on behavior. In three separate experiments, we extended earlier work by Miller and Kelly (1975) that examined the behavioral effects of microinfusion of cholera toxin (CTX) into the nucleus accumbens (N. Acc.) in rats. CTX is a bacterial toxin that ADP-ribosylates the Gs transducer protein and stimulates production of cAMP. For Experiment I, three groups of rats received either saline or CTX (50 or 500 ng/microliter) into the N. Acc. Locomotor activity was measured for 4 hr following a single CTX infusion and subsequently for 4 hr on 6 consecutive days. No acute effects on motor activity were observed. However, the 500 ng dose of CTX induced long-lasting hyperactivity that was apparent 24 hr later and that lasted 4 d. A smaller but significant hypermotility occurred on days 4 and 5 following infusion of the 50 ng dose. Site specificity of this effect was investigated in Experiment II by infusion of CTX (250 ng/microliter) into either the N. Acc. or the posterior dorsal striatum (PDS). CTX treatment of the PDS had no behavioral effects while the long-lasting hyperactivity following treatment of the N. Acc. was replicated. In Experiment III the effect of intra-accumbens pretreatment with saline or CTX (10 ng/microliter) on d-amphetamine (0.5 mg/kg, i.p.)- and cocaine (7 mg/kg, i.p.)-induced motor activity was investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501513 TI - Basal versus apical dendritic long-term potentiation of commissural afferents to hippocampal CA1: a current-source density study. AB - Current-source density analysis was used to estimate the magnitude of the synaptic excitation at the basal and apical dendritic synapses of CA1 following commissural stimulation in the urethane-anesthetized rat, before and after a theta-frequency patterned primed burst tetanus. Stimulation of the contralateral CA3 or the contralateral CA1 stratum oriens excited both the basal and apical dendrites in CA1 about equally. However, primed burst tetanization of the contralateral CA3 or CA1 stratum oriens resulted in significant long-term potentiation (LTP) only at the basal dendrites and not at the apical dendrites. Stimulation of the contralateral CA1 stratum radiatum excited the apical dendrites more than the basal dendrites of CA1, but tetanization of this contralateral site gave little change in the apical or basal dendritic excitation. Tetanization of the contralateral CA1 stratum radiatum after an intraventricular administration of bicuculline, a GABAA antagonist, however, resulted in significant LTP at both the apical and basal dendrites. It was concluded that, in the intact hippocampus in vivo, the threshold for LTP at the commissural apical dendritic synapse was high in comparison to that at the basal dendritic synapse and this high threshold may be partly caused by inhibitory interneurons that predominantly synapsed on the apical dendrites. Thus, the basal and apical dendrites of the CA1 pyramidal cells are not equal in their propensity for long-term plasticity. PMID- 8501514 TI - Involvement of a metalloprotease in low-affinity nerve growth factor receptor truncation: inhibition of truncation in vitro and in vivo. AB - The mechanism of low-affinity NGF receptor (LNGFR) truncation was investigated in cultured Schwann cells. Affinity labeling of Schwann cells with 125I-NGF or metabolic labeling with 35S-cysteine showed that truncated NGF receptor (NGF-Rt) was derived from the cell surface form of the receptor. Addition of full-length, exogenous NGF receptor (M(r) = 80 kDa) to Schwann cell membranes resulted in cleavage of the exogenous substrate to NGF-Rt. Investigations into the mechanism of truncation revealed that metalloprotease inhibitors such as phenanthroline, bathophenanthroline, and 8-hydroxyquinoline (8-OHQ) blocked LNGFR truncation in a concentration-dependent fashion. Inhibitors of other protease classes had no effect on truncation. In addition, truncation did not occur at 4 degrees C. It was found that truncation could also occur in Schwann cell membrane preparations, indicating that the putative protease was membrane bound and closely associated with the LNGFR. Metal reconstitution experiments revealed a strong preference toward zinc for the truncating activity, with iron and manganese having slight reconstitution activity in phenanthroline-quenched membranes. To determine if apparent truncation could be inhibited in vivo, the metalloprotease inhibitor 8 OHQ was administered to neonatal rats. 8-OHQ resulted in decreased urine and blood NGF-Rt levels and increased the sciatic nerve LNGFR content; this effect was dose dependent. In adult rats with sciatic nerve crush lesions, 8-OHQ (30-300 mg/kg, t.i.d.) significantly enhanced the rate of sensory neuron regeneration as assessed by the nerve pinch assay. This was accompanied by increased levels of LNGFR in distal nerve segments. These results suggest that Schwann cells possess a metalloprotease-like activity that serves to cleave LNGFR from the surface of these cells. We propose that the putative metalloprotease represents a novel mechanism by which the Schwann cell regulates this particular cell surface protein. Furthermore, increasing the amount of Schwann cell surface LNGFR appears to be of functional significance in that sensory nerve regeneration can be enhanced by inhibition of truncation. PMID- 8501515 TI - An 83 kDa O-GlcNAc-glycoprotein is found in the axoplasm and nucleus of Aplysia neurons. AB - Glycoproteins containing O-linked N-acetylglucosamine (O-GlcNAc) are present in axons of Aplysia neurons (Gabel et al., 1989) and among transcription factors and other proteins in the nucleus of eukaryotic cells (Jackson and Tjian, 1988). A recently discovered pathway in neurons transports proteins through the axon and then into the nucleus (Ambron et al., 1992). If any of the axonal O-GlcNAc glycoproteins use this pathway, then the axon and the nucleus will have these glycoproteins in common. We addressed this issue by using galactosyltransferase and UDP-3H-galactose to label and identify the glycoproteins in three regions of Aplysia neurons: axoplasm, extruded from nerves; nuclei, isolated by manual dissection of single neurons; and cytoplasm, obtained after removal of nuclei. At least 21 glycoproteins were labeled by this procedure; several, at 200, 180, 83, 76, and 66 kDa, from the nucleus and axoplasm comigrated after SDS-PAGE. Radiolabeled galactosyl-N-acetylglucosaminitol was released from the glycoproteins by base/borohydride, thereby verifying the presence of O-GlcNAc. Comparison of the 83 kDa glycoprotein from the nucleus and axoplasm revealed that both were soluble, had multiple O-GlcNAcs, and were bound to WGA. Thus, the 83 kDa constituent is a good candidate to use the axonal transport/nuclear import pathway. PMID- 8501516 TI - Lesions of the perirhinal and parahippocampal cortices in the monkey produce long lasting memory impairment in the visual and tactual modalities. AB - Compared to normal animals, monkeys with bilateral lesions of the perirhinal and parahippocampal cortices (PRPH lesion) were impaired on both a visual and a tactual version of the delayed nonmatching to sample task. In addition, the memory deficit was long-lasting, as indicated by the finding of a significant deficit when the visual version of the delayed nonmatching to sample task was readministered approximately 2 years after surgery. Animals with PRPH lesions performed normally on discrimination tasks in the visual and tactual modalities. Multimodal and long-lasting memory impairments are defining characteristics of human medial temporal lobe amnesia. Accordingly, these results demonstrate important parallels between the memory deficit associated with PRPH lesions and human medial temporal lobe amnesia. These data, taken together with previous findings, suggest that the perirhinal and parahippocampal cortices play an important role in memory function and that these cortical areas are critical components of the medial temporal lobe memory system. PMID- 8501517 TI - Induced cell death in a thalamic nucleus during a restricted period of zebra finch vocal development. AB - A discrete network of forebrain nuclei underlies vocal learning and production in male zebra finches. Three nuclei within this network form a neural pathway that is particularly important for vocal learning in juveniles: area X of the avian striatum projects to the medial dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of any of these nuclei in juvenile birds disrupt normal vocal development, whereas the same lesions in adult birds have no effect on already-learned song. Because numerous studies have shown that neuronal survival in the developing nervous system depends on access to efferent targets, we have investigated the possibility that the survival of DLM neurons is similarly regulated over the course of vocal learning. Thus, the efferent target of DLM (IMAN) was lesioned electrolytically in male birds at various stages of vocal development (20, 40, 60 d of age and adult) and birds were killed either 2, 4, or 6 d postlesion. Electrolytic lesions of IMAN removed the single identified efferent target of DLM projection neurons and axotomized the terminal arborizations of these neurons. Although DLM does not normally lose neurons during vocal development, IMAN lesions in 20-d-old birds yielded numerous pyknotic cells throughout DLM by 4 d postlesion and a two-thirds reduction in DLM neuron density by 6 d postlesion. In contrast, IMAN lesions in adult birds had little or no effect on neuronal survival in DLM. Analysis of 40-d-old birds revealed significant but less substantial cell loss than in 20-d-old birds, whereas 60-d-old birds were not different from adults. The age-related decline in the vulnerability of DLM cells to IMAN lesion-induced death suggests that factors that regulate DLM neuron survival may also be involved in the acquisition of learned vocal behavior in songbirds. PMID- 8501518 TI - Motor innervation of dorsoventrally reversed wings in chick/quail chimeric embryos. AB - In the limb plexus, motor axons destined for limb muscles diverge along separate pathways to innervate muscles derived from either the dorsal or ventral premuscle masses. We have examined the axonal guidance cues involved in this initial, specific pathway choice at the plexus by making dorsoventral (D/V) limb bud reversals prior to innervation. Chick/quail chimeras were used to determine the proximodistal level of the reversal in tissue sections. The specificity of the projections to dorsal or ventral nerve trunks was assessed by retrograde HRP labeling at ages prior to motoneuron death. Axons corrected for the reversal when the level of the graft was proximal to the plexus, and when the reversed limb and its gross nerve pattern were normal. If all of these conditions were not satisfied, aberrant innervation patterns were observed. Axonal trajectories were analyzed within the host tissue, at the host-graft border, and within rotated tissue to determine where along the pathway guidance cues might be located. Special attention was given to cases in which axons compensated for the reversal to project in accord with the positions of their soma in the lateral motor column. In these correcting cases, after normal D/V sorting in the spinal nerves of the host, motor axons altered their trajectories upon entering rotated graft tissue as they approached and traversed the plexus. Because corrections were within rotated tissue and not proximal to it, the D/V pathway cues are unlikely to be long-range target-derived signals, but rather appear to be closely associated with positional information in the plexus region and also more proximally in the tissue surrounding the distal spinal nerves. PMID- 8501519 TI - Semisynthetic sphingolipids prevent protein kinase C translocation and neuronal damage in the perifocal area following a photochemically induced thrombotic brain cortical lesion. AB - A vascular thrombotic lesion localized to the rat sensorimotor cortex was produced following intravenous injection of the photosensitive dye rose bengal, and its activation with a small beam of high-intensity white light focused to the skull overlaying the sensorimotor cortex. In the sensorimotor cortex at various times after the triggering event, two contiguous brain regions with different degree(s) of neuronal damage can be distinguished: (1) a primary thrombotic ischemic core where the majority of cells are dead and (2) a penumbra region surrounding the core lesion in which a slower progressive neuronal degeneration is occurring. Importantly, in both brain regions the neuronal degeneration is associated with the activation and persistent translocation of protein kinase C (PKC) as indicated by an increase in 4-beta-3H-phorbol-12,13-dibutyrate (3H-PDBu) binding. Moreover, the demonstration that in the area penumbra the neuronal degeneration and the persistent translocation of PKC can be inhibited by a pretreatment with dizocilpine (i.e., MK-801) indicates that the dynamics of the progression of the neuronal degeneration are maintained by glutamate accumulating in the extraneuronal fluids. MK-801 additionally prevents the transcriptional activation of several immediate-early genes (IEGs) (e.g., c-fos) and their cognate third nuclear messenger (i.e., c-Fos) expression present in the hemisphere ipsilateral to the lesion. On the other hand, LIGA4 and LIGA20 derivatives of GM1 lysoganglioside reduce the membrane translocation of PKC and the neuronal damage in the penumbra area, but fail to change the increase of IEG expression in the cortex ipsilateral to the lesion. PMID- 8501520 TI - Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease. AB - A two-site ELISA and a bioassay were used to detect NGF-like activity in human brain tissue. Both assays detected mouse NGF and recombinant human NGF with approximately equal sensitivity, whereas the antibodies showed little cross reactivity with the recombinant human proteins NT-3 and brain-derived neurotrophic factor. NGF-like activity was detected in fresh human cortical samples obtained from epileptic patients, with the highest activity observed in the right hemisphere of men. NGF-like activity was subsequently measured in autopsy samples of frontal and occipital cortex from patients with Alzheimer's disease (AD) and from individuals with no history or pathological evidence of AD. Based on both the ELISA and the bioassay measurements, NGF-like activity was significantly elevated in both brain regions in AD. These results demonstrate the feasibility of detecting NGF-like activity in both fresh and postmortem human brain tissue and further suggest that AD is characterized by increased, rather than decreased, levels of cortical beta-NGF. The AD-related increase in NGF may be a consequence of degenerative changes in the basal forebrain cholinergic system. PMID- 8501521 TI - Cellular distribution of dopamine D1 and D2 receptors in rat medial prefrontal cortex. AB - The relative distribution and cellular localization of the dopamine D1 and D2 receptor subtypes were assessed in frozen sections of rat medial prefrontal cortex (mPFC). The D1 and D2 receptor binding sites were labeled with the selective high-affinity antagonists SCH 23390 and N-(p-aminophenethyl)-spiperone (NAPS), respectively, coupled to either Bodipy or Texas red fluorophores. Under the incubation conditions employed, kinetic, competition, and selectivity studies showed that these modified ligands retained pharmacological selectivity. Optimal binding fluorescence was at 100 nM of each ligand, and fluorescence increased linearly from 1 to 15 min of incubation at 2 degrees C. NAPS-Texas red binding fluorescence was inhibited with 10 nM quinpirole (D2 agonist), but not 10 nM SKF 38393 (D1 agonist), while SCH 23390-Texas red binding was inhibited with SKF 38393, but not quinpirole. The localization of dopamine receptor binding was assessed in montages constructed from low-magnification photomicrographs through the depth of the cortex, or in corresponding high-magnification photomicrographs. Cells showing D1- or D2-like receptor binding fluorescence were present in layers II-VI, with the highest density observed in layers V and VI. The addition of mianserin (100 nM, 5-HT2 antagonist) to incubated sections slightly reduced the numbers of labeled cells in each cortical layer, but retained the preferential localization to the deeper layers. Two separate observations supported the idea that the fluorescently coupled ligands were localized to neuronal cell bodies. First, receptor labeling with the fluorescently coupled ligands co-localized almost exclusively to cells in the cortical mantle showing neuron-specific enolase immunoreactivity. Second, a comparison of the cell size distribution taken from adjacent Nissl-stained sections with the size of cells showing D1- or D2-like receptor binding fluorescence revealed complete overlapping of fluorescence with neuronal cell bodies. In mPFC layer VI, the size of cells showing D1-like receptor binding fluorescence was 77.8 +/- 5.1 microns2, similar to non-pyramidal neurons, while that for D2-like receptor binding fluorescence was 108.2 +/- 4.5 microns2, consistent with both large interneurons and small pyramidal cells. Only a small percentage of cells showing D1- or D2-like receptor binding overlapped in size with glia, but this occurred almost exclusively within the white matter region below the cortical mantle. These findings are consistent with the hypothesis that the D1 and D2 receptor subtypes are found on different populations of neurons, although some overlap probably occurs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501522 TI - Delayed pattern discrimination in patients with unilateral temporal lobe damage. AB - Behavioral and neurophysiological studies in macaque monkeys suggest a role of the inferior temporal cortex in pattern discrimination and visual memory. To determine whether this cortical area is also involved in human short-term visual memory, we measured spatial frequency discrimination thresholds for sequentially presented stimuli in 17 patients with unilateral, postoperative focal damage to the temporal cortex (11 left, 6 right hemisphere). These results are compared to those of 17 age-matched control subjects. Contrast detection thresholds and difference thresholds for spatial frequency were determined for spatially truncated sine wave gratings presented in the left and right visual fields. Detection thresholds were measured for sine wave gratings in a spatial two alternative forced-choice procedure for three spatial frequencies [2.5, 5, and 10 cycles (c)/degree] for each hemifield. Discrimination thresholds were determined for two gratings sequentially presented either 4 degrees to the left or right of fixation. Grating contrast was five times the value of detection threshold and reference frequency was 5 c/degree. Within each trial, the gratings were separated in time by 1, 3, and 10 sec interstimulus intervals (ISIs), and subjects signaled which grating had the higher spatial frequency. The results indicate that (1) contrast detection thresholds overall did not differ between patient and control groups; (2) spatial frequency discrimination thresholds were, however, significantly elevated in patients and this elevation was significantly more pronounced in the visual field contralateral to the damaged hemisphere; and (3) patients with inferotemporal damage exhibited higher discrimination thresholds for the longest ISI, whereas patients with medial/superior temporal lobe damage did not show this effect. The results suggest that visual areas in human temporal cortex are involved in the higher visual processes underlying delayed pattern discrimination. PMID- 8501523 TI - In vivo development of voltage-dependent ionic currents in embryonic Xenopus spinal neurons. AB - Initial evidence that electrical excitability is both an early aspect of neuronal differentiation and a developmentally regulated property was obtained from recordings of action potentials in vivo. Subsequently, the analysis of the underlying voltage-dependent currents during early stages of embryogenesis was facilitated by investigation of dissociated neurons and muscle cells differentiating in culture. Calcium and potassium currents play a major role in the differentiation of the action potential of Xenopus spinal neurons, and calcium influx triggers specific features of neuronal differentiation. However, the extent to which differentiation of currents in vitro parallels that in vivo is uncertain. We have undertaken a study of in vivo differentiation of these macroscopic currents in Xenopus embryos. Spinal cords were isolated from embryos at several early stages of neurogenesis. Neurons in these isolated spinal cords were accessible to patch-clamp electrodes. Neuronal currents were recorded within 1 hr to assure that the characteristics of the currents resulted from developmental events occurring in vivo prior to the experiment. Whole-cell voltage-clamp recordings from neurons in these acutely isolated and intact embryonic spinal cords demonstrate that both the delayed-rectifier and inactivating potassium current and a low-voltage-activated calcium current mature in a manner closely parallel to that observed in culture. The results validate those from the culture system and indicate that the spinal cord is another region of the CNS accessible to cellular analysis in an intact preparation. PMID- 8501524 TI - Selective loss of hippocampal granule cells following adrenalectomy: implications for spatial memory. AB - We examined the effects of long-term adrenalectomy (ADX) on hippocampal anatomy and behavioral learning in two spatial memory tasks. We assessed damage throughout the hippocampus by stereological analysis of the dentate gyrus and Ammon's horn. Rats were ADX or sham operated, and then tested in the Morris water maze 12 weeks after surgery, followed by testing on an eight-arm, alternating baited radial maze at 22 weeks postsurgery. Animals were killed 7 1/2 months after surgery. ADX rats had selective volume reduction in the dentate gyrus with no changes in pyramidal regions CA1, CA2, CA3, or CA4. Dentate gyrus damage in some cases occurred throughout the entire rostrocaudal extent of the hippocampus. Analysis of corticosterone serum levels, serum Na+/K+ ratios, and body weight gain suggested that individual differences in dentate gyrus damage appear to be due to incomplete adrenalectomies or remaining ectopic tissue. ADX rats were able to learn in both the Morris water maze and eight-arm radial maze, even when the dentate gyrus was severely damaged (80% volume reduction). However, in the Morris water maze, the ADX rats' learning rate was significantly slower compared to controls. There was no difference between ADX and controls during reversal in either task. These data indicate that damage to the dentate gyrus following long term ADX is severe enough to cause learning impairment in selected learning tasks. Such damage is restricted to the dentate gyrus and can occur throughout the rostrocaudal regions of the hippocampus. PMID- 8501525 TI - Extrinsic factors influence the expression of voltage-gated K currents on neonatal rat sympathetic neurons. AB - Voltage-gated potassium (K) currents are important in controlling a neuron's excitability. We have shown previously (McFarlane and Cooper, 1992) that neonatal superior cervical ganglia (SCG) neurons express three voltage-gated K currents: a noninactivating delayed-rectifier type current (IK), a rapidly inactivating A current (IAf), and a slowly inactivating A-current (IAs). When grown in culture for 4 weeks without other cell types, SCG neurons lose their expression of IAf and IAs, suggesting that an extrinsic factor(s) is involved in controlling the expression of these currents. In vivo, SCG neurons are surrounded by non-neuronal cells. Therefore, in this study we investigated whether the ganglionic non neuronal cells provide a factor required for A-current expression. We show that postnatal day 1 (P1) SCG neurons continue to express IAf and IAs when cocultured with their ganglionic non-neuronal cells. Medium conditioned by ganglionic non neuronal cells mimics the non-neuronal cell influence on IAf and IAs expression, suggesting that the effects of non-neuronal cells are mediated by way of a secreted factor. Ciliary neurotrophic factor, a factor present in peripheral non neuronal cells, had similar effects to those of ganglionic cell-conditioned medium. Moreover, we find that the dependence of IAf on a non-neuronal cell factor is developmentally regulated; P14 neurons grown in culture without other cell types continue to express IAf. However, IAs on P14 neurons maintains its dependence on a factor from non-neuronal cells. Finally, in addition to extrinsic control of voltage-gated K currents, we suggest that SCG neurons use intrinsic mechanisms to coordinate their expression of IAf, IAs, and IK such that changes in one K current are compensated for by reciprocal changes in one or more of the other K currents. PMID- 8501526 TI - Specific high-affinity receptors for neurotrophin-3 on sympathetic neurons. AB - When used at concentrations allowing interactions only with its high-affinity receptors, neurotrophin-3 (NT-3) promotes the survival of sensory neurons isolated from embryonic day 8 (E8) chicks, but not the survival of E11 sympathetic neurons. These sympathetic neurons (which can be rescued by the addition of NGF) display high-affinity receptors for NT-3 (Kd of 1.6 x 10(-11) M) that cannot be distinguished from the high-affinity NT-3 receptors on sensory neurons using equilibrium binding or kinetic criteria. This represents the first example of embryonic neurons that cannot be rescued by the in vitro addition of a neurotrophin in spite of the presence of corresponding neurotrophin high-affinity receptors. At elevated concentrations, beyond the saturation of its high-affinity receptors, NT-3 supports the survival of some E11 sympathetic neurons, an effect that might be mediated by the high-affinity NGF receptor. Using E7 sympathetic neurons, about 40% of the cells initially plated can be rescued in vitro by the addition of low concentrations of NT-3 (but not of NGF) and produce profuse neurites. This indicates that NT-3 may play a role in the early development of some sympathetic neurons. PMID- 8501527 TI - Temporal changes in beta-tubulin and neurofilament mRNA levels after transection of adult rat retinal ganglion cell axons in the optic nerve. AB - Axons of adult mammalian retinal ganglion cells (RGCs) do not regenerate spontaneously after injury in the optic nerve and show a persistent decrease in the rate of transport of tubulin and neurofilament proteins. To investigate further the expression of cytoskeletal proteins in these axotomized CNS neurons, mRNA levels of beta-tubulin and the 150 kDa neurofilament subunit (NF-M) were measured after interrupting the optic nerve 9 mm from the eye. Northern blots of RNA extracted from whole retinas after optic nerve transection showed that the total level of both of these mRNAs fell after injury. To determine if this decrease was a result of the death of axotomized RGCs or reflected changes in individual neurons, RNA probes were hybridized to radial cryostat sections of normal and axotomized retinas from 1 d to 6 months after injury. Grain counts revealed two trends of tubulin expression in RGCs. An early increase in tubulin mRNAs in the axotomized RGCs was followed by a later decrease. Such an increase in tubulin mRNA levels has been correlated with regenerative growth in other neurons. By 1 week after injury, the beta-tubulin mRNA levels decreased to 70% of the control value. Moreover, the time of this fall coincided with the onset of a marked slowing of cytoskeletal transport that follows injury in the optic nerve. In contrast, NF-M mRNA levels dropped immediately after axotomy, and remained at 80% of the control level. It is suggested that the transient increase in tubulin mRNAs may reflect an early regenerative response whose persistence depends on further growth cone interactions with the substrate. PMID- 8501528 TI - The development of synaptic function and integration in the central auditory system. AB - The development of inhibitory synaptic transmission is difficult to assess because the afferents usually arise from intrinsic neurons that are difficult to stimulate independently. The postnatal maturation of excitatory and inhibitory synaptic function was compared in the gerbil lateral superior olive (LSO), where it is possible to stimulate physically discrete afferent projections. Intracellular recordings obtained in a brain slice preparation revealed that transmission was prominent at birth. The EPSPs and IPSPs were up to 2 orders of magnitude longer than in more mature animals. Brief trains of electrical stimulus pulses led to a temporal summation of postsynaptic potentials (PSPs) in 1-14 d animals resulting in prolonged depolarizations or hyperpolarizations. In neonates, the depolarization could exceed 1 sec following a 70 msec stimulus train. The IPSPs in neonates were often of sufficient amplitude to evoke a rebound depolarization or action potential. The number of converging afferents was estimated from the quantized increases in PSP size. There was a significant decrease with age, suggesting that both inhibitory and excitatory afferents were eliminated during the first 3 postnatal weeks. The integration of action potentials with IPSPs was examined with conjoint stimuli to the two afferent pathways, and demonstrated that the effective IPSP duration decreased approximately 20-fold during the first 3 postnatal weeks. The magnitudes and durations of electrical stimulus-evoked PSPs suggest that spontaneous discharge of afferents to the LSO could have a substantial impact on their development, even prior to the response to airborne sound at 12 d. Furthermore, the synaptic responses obtained at 12-14 d postnatal indicated that both amplitude and temporal processing remain compromised. These immature synaptic properties would be expected to compound the inadequacies present in the cochlea and cochlear nucleus. PMID- 8501529 TI - Role of calcium in astrocyte volume regulation and in the release of ions and amino acids. AB - Primary astrocyte cultures exposed to hypotonic media undergo a rapid initial swelling followed by a regulatory volume decrease (RVD), which is associated with the release of ions and amino acids. The Ca2+ dependence of RVD was investigated. Using a method that measures extracellular electrical resistance to measure cell volume changes in substratum-attached cells, we found that when astrocytes were exposed to hypotonic media without calcium, RVD was abolished. The addition of CaCl2 to astrocytes swollen in hypotonic media without calcium caused an almost immediate initiation of volume regulation, with an EC50 of approximately 0.1 mM CaCl2. Swelling of astrocytes in hypotonic medium caused an increased influx of 45Ca2+, which was partially blocked (60%) by 1 microM nimodipine, suggesting that voltage-gated L-type calcium channels were being opened. Previous work had shown that hypotonic media-induced swelling of astrocytes caused membrane potential depolarizations sufficient to open such channels (Kimelberg and O'Connor, 1988). By measuring intracellular free calcium with fura-2, we found that astrocytes swollen in hypotonic medium showed a rapid increase in [Ca2+]i, reaching a peak of approximately 600 nM, followed by a decrease to a sustained plateau (approximately 250 nM) mirroring the time course of volume regulation. The removal of extracellular calcium totally abolished, and the addition of 1 microM nimodipine partially abolished the elevated plateau, while neither affected the initial [Ca2+]i peak. These data suggest that the initial peak of the hypotonic induced rise in [Ca2+]i is caused by release from intracellular stores and that the sustained elevated plateau is due to extracellular calcium influx. The removal of extracellular calcium also abolished swelling-induced K+(86Rb) and 36Cl- efflux, but did not affect the swelling-induced release of 3H-D-aspartate, or 3H-taurine (data not shown). These data indicate that hypotonic-induced aspartate and taurine release is not necessary for RVD in astrocytes swollen by exposure to hypotonic media, since RVD is completely inhibited by the omission of external Ca2+. The addition of 1 mM quinine HCl, which is known to block Ca(2+) activated K+ channels, also abolished both volume regulation and 86Rb+ efflux in hypotonic media-swollen astrocytes in the presence of medium calcium, but did not affect 3H-D-aspartate efflux. We suggest that the swelling of astrocytes in hypotonic media which leads to a rapid membrane depolarization first opens voltage-gated calcium channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501530 TI - Coexpression of multiple acetylcholine receptor genes in neurons: quantification of transcripts during development. AB - A large family of genes encoding subunits of nicotinic ACh receptors (AChRs) has been identified in vertebrates and shown to be expressed in the nervous system. The multiplicity of genes raises questions about which gene products coassemble to produce native receptor subtypes and how the expression of receptor genes is regulated in neurons. We report here that five neuronal AChR genes are expressed in the chick ciliary ganglion at both early and late times in development. Quantitative RNase protection experiments demonstrated that at embryonic day 18 (E18) the ganglion contains about 1800 copies of alpha 7 transcript per neuron, 900 copies of alpha 3 transcript per neuron, and 200-300 copies each of alpha 5, beta 2, and beta 4 transcripts per neuron. The same five genes are expressed at significantly lower levels at E8 but show the same rank order of abundance in transcripts per neuron. Few, if any, transcripts were found for the alpha 2, alpha 4, alpha 8, and beta 3 AChR genes in ciliary ganglion RNA at either E8 or E18. The 6- and 13-fold increases previously reported for two classes of AChRs on the neurons between E8 and E18 approximate the 4-14-fold increases observed here in AChR gene mRNA levels per neuron over the same time period. The alpha 3, alpha 5, alpha 7, and beta 4 genes have previously been correlated with subunits of ciliary ganglion AChRs, but the beta 2 gene has not. The abundance of beta 2 transcripts raises the possibility either that the known AChRs in the ganglion have a more complex subunit composition than previously described or that additional receptor subtypes remain to be discovered. Northern blot analysis revealed no changes in transcript pattern for the alpha 3, alpha 5, and beta 4 genes between E8 and E18; a small change may occur in the transcript pattern for the alpha 7 gene. In situ hybridizations demonstrated that alpha 5 and beta 4 transcripts are expressed in essentially all ciliary ganglion neurons as has been shown previously for the more abundant alpha 3 transcript and inferred for the alpha 7 transcript. The results indicate that neurons can stably coexpress multiple AChR genes, including three of the alpha type, and that transcript levels may be rate limiting for accumulation of AChRs during development. PMID- 8501531 TI - Rapid communication between neurons and astrocytes in primary cortical cultures. AB - The identification of neurotransmitter receptors and voltage-sensitive ion channels on astrocytes (reviewed by Barres, 1991) has renewed interest in how these cells respond to neuronal activity. To investigate the physiology of neuron astrocyte signaling, we have employed primary cortical cultures that contain both neuronal and glial cells. As the neurons in these cultures exhibit synchronous spontaneous synaptic activity, we have used both calcium imaging and whole-cell recording techniques to identify physiological activity in astrocytes related to neuronal activity. Whole-cell voltage-clamp records from astrocytes revealed rapid inward currents that coincide with bursts of electrical activity in neighboring neurons. Calcium imaging studies demonstrate that these currents in astrocytes are not always associated with slowly propagating calcium waves. Inclusion of the dye Lucifer yellow within patch pipettes confirmed that astrocytes are extensively coupled to each other but not to adjacent neurons, indicating that the currents observed are not due to gap junction connections between these cell types. These currents do not reflect widespread diffusion of glutamate or potassium released during neuronal activity since a population of small, round, multipolar presumed glial cells that are not dye coupled to adjacent cells did not display electrical currents coincident with neuronal firing, even though they respond to locally applied glutamate and potassium. These findings indicate that, in addition to the relatively slow signaling conveyed by calcium waves, astrocytes also display rapid electrical responses to neuronal activity. PMID- 8501532 TI - Evidence for "preterminal" nicotinic receptors on GABAergic axons in the rat interpeduncular nucleus. AB - Presynaptic nicotinic ACh receptors (nAChRs) are abundant in the nervous system, where they are thought to regulate the release of various neurotransmitters. Whole-cell recordings performed on rat interpeduncular nucleus neurons using the thin-slice technique showed that nicotine dramatically increased the frequency of postsynaptic GABAergic currents. This effect was observed at low micromolar concentration of agonist; it was mimicked by cytisine, dimethylphenylpiperazinium, and ACh in the presence of eserine. It was blocked by hexamethonium, dihydro-beta-erythroidine, and mecamylamine. The presynaptic action was suppressed in the presence of TTX. A comparable effect of nicotine was found using a preparation of acutely isolated neurons that had retained synaptic terminals attached to their cell body as evidenced by immunoreactivity to synaptophysin and presence of spontaneous GABAergic and glutamatergic synaptic activity. Nicotinic agonists increased the frequency of GABAergic postsynaptic currents, an effect blocked by curare and mecamylamine. This action was also suppressed in the presence of TTX. These data suggest the presence of nAChRs at a preterminal level on axons of intrinsic GABAergic neurons. We propose that, in contrast to presynaptic nAChRs, activation of these "preterminal" nAChRs can trigger a spike discharge and thus have a generalized action on the GABAergic afferent. PMID- 8501533 TI - C-fos expression in the pons and medulla of the cat during carbachol-induced active sleep. AB - Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c-fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c-fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state. PMID- 8501534 TI - Mutually exclusive expression of alternatively spliced FMRFamide transcripts in identified neuronal systems of the snail Lymnaea. AB - The FMRFamide gene of the snail Lymnaea encodes tetrapeptides (FMRFamide/FLRFamide) and heptapeptides (GDPFLRFamide/SDPFLRFamide) on separate exons. In situ hybridization probes specific to these exons were used to map the expression of the two exons in identified neuronal systems of the CNS. Analysis of more than 200 preparations showed that cytoplasmic expression of mRNA was exclusively of one type, with individual neurons expressing either the tetrapeptide or heptapeptide exon. Of the approximately 340 neurons expressing the two exons, the majority (80%) expressed the tetrapeptide exon. The tetrapeptide exon was more widespread, occurring in neurons from all 11 ganglia of the CNS. The heptapeptide was mainly confined to two ganglia (visceral and right parietal), with a small number of cells in three other ganglia. Mapping studies combined with dye marking of identified neurons showed the presence of the tetrapeptide exon in several behaviorally important networks: heart motoneurons, whole body withdrawal response motoneurons, and probably penis motoneurons as well as giant identified neurons (LP1, RPD1). The heptapeptides were prominent in two main clusters of cells (Bgp and Fgp) together with a smaller number of tetrapeptide-expressing cells. PMID- 8501535 TI - Motor axons preferentially reinnervate motor pathways. AB - Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal motor branches and/or muscle, a process termed "preferential motor reinnervation." Collaterals of a single motor axon often enter both sensory and motor Schwann cell tubes of the distal stump; specificity is generated by pruning collaterals from sensory pathways while maintaining those in motor pathways. Previous experiments in the rat femoral nerve model evaluated reinnervation of the femoral motor branch and quadriceps muscle as a unit. In this study, pathway contributions are analyzed separately by denying muscle contact, or by reinnervating muscle through inappropriate, formerly sensory pathways. Motor axons preferentially reinnervate motor pathways, even when these pathways end blindly in a silicon tube. If the femoral nerve is removed as a graft and reinserted with correct or reversed alignment of the sensory and motor branches, more motoneurons reinnervate muscle through correct motor than through incorrect sensory pathways. Motor pathways thus differ from sensory pathways in ways that survive Wallerian degeneration and transplantation as a graft, and that can be used by regenerating motor axons as a basis for collateral pruning and specificity generation. PMID- 8501536 TI - Expression of the nuclear membrane protein statin in cycling cells. AB - Statin is a 57 kD protein previously reported to be expressed by cells in G0. We have studied the detailed distribution of statin immunoreactivity in normal human and rat tissues, and correlated this with investigation of in vitro model systems. By laser confocal microscopy, statin immunoreactivity is localized to the nuclear membrane. In contrast to previous reports, using in vitro model systems we found that statin was also expressed by replicating cells as judged by both co-localization with [3H]thymidine-labelled and Ki67-labelled cells. Furthermore, in a nude mouse xenograft model the number of statin-labelled cells exceeded the number of quiescent cells as assessed by both fraction of labelled mitosis methods and labelling with [3H]thymidine and Ki67. We conclude that although there is an association between expression of the 57 kD nuclear membrane protein statin and growth arrest, this is not absolute and it is expressed in a sub-population of cycling cells. The properties of statin closely resemble those of nuclear lamins, members of the intermediate filament family. PMID- 8501537 TI - Retinoblastoma (Rb) gene product expression in lymphomas. Correlation with Ki67 growth fraction. AB - The retinoblastoma susceptibility gene (Rb) has been characterized as a tumour suppressor gene. Rb protein is involved in cell-cycle control, regulating gene transcription. The absence of Rb protein in inherited retinoblastoma has been proved to be the result of inactivation of both Rb alleles through mutation or deletion, according to the general model for suppressor genes. The frequent detection of Rb gene alterations in human tumours (retinoblastoma, osteosarcoma, bladder carcinoma, small-cell lung carcinoma) and the correlation with clinical outcome found in some tumours prompted us to study Rb gene expression in lymphoid tumours in an attempt to determine whether Rb gene expression is related to histological type and degree of aggressivity in human lymphomas. To establish normal levels of Rb protein, its expression was analysed in vitro on cytospin preparations from normal and pokeweed mitogen (PWM) or phytohaemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBLs), using a monoclonal antibody (PMG3 245). Rb protein expression in vivo was quantified using a computer analysis system (CAS) on frozen sections from reactive and neoplastic lymphoid tissue. As a control of tissue preservation, and to compare Rb expression and growth fraction, the tumours and cells were labelled simultaneously with the Ki67 monoclonal antibody. Normal and stimulated lymphocytes showed a gradual increase of Rb protein during progression of the cell cycle, with a peak in the M phase. G0-G1 cells had no detectable levels of Rb protein, suggesting that the Rb gene may act as a 'status quo' cellular growth fraction control mechanism. In reactive lymphoid tissue, Rb protein was mainly expressed in germinal centres (lymph nodes, tonsils) and cortical thymocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501538 TI - Immunohistochemical staining of ras oncogene product in neoplastic and non neoplastic mesothelial tissues: immunoreactivity for N-ras and lack of immunohistochemical staining for Ha-ras and K-ras. AB - Immunohistochemical staining of 36 malignant mesotheliomas and 45 cases of non neoplastic mesothelium including 20 specimens with signs of hyperplasia were investigated using murine monoclonal antibodies directed against p21 ras protein, Ha-ras protein, K-ras protein, and N-ras protein. All cases of non-neoplastic mesothelium and the majority of the malignant mesotheliomas (78 per cent) showed cytoplasmic and often submembranous immunoreactivity in more than 50 per cent of the cells with both the pan-ras and N-ras antibody. No immunoreactivity was observed for Ha- and K-ras. There was no statistically significant difference with respect to immunoreactivity between neoplastic and non-neoplastic mesothelium or between the various mesothelioma subtypes. PMID- 8501539 TI - p53 immunoreactivity in inflammatory and neoplastic diseases of the uterine cervix. AB - Immunoreactivity for the tumour suppressor gene product p53 is commonly found in many different human malignancies and few premalignant lesions. Data on cervical neoplasms, however, are still lacking. We retrospectively investigated p53 immunoreactivity in 92 lesions of the uterine cervix, including 44 cases of chronic cervicitis, 29 squamous intraepithelial lesions (SILs), and 19 invasive carcinomas. p53 immunoreactivity, confined to the basal cell layer, was detected in 74 per cent of cases showing chronic cervicitis and in all cases with low grade SILs. Conversely, suprabasal and/or diffuse p53 immunoreactivity was exclusively demonstrated in 25 per cent of high-grade SILs and in 74 per cent of invasive carcinomas. The results of this investigation document a high prevalence of p53-immunoreactive malignant tumours of the uterine cervix. In high-grade SILs, p53-immunoreactive cells paralleled the height of involvement by dysplastic changes within the squamous epithelium. A prolonged half-life of the protein is the most likely explanation for the occurrence of p53 immunoreactivity in neoplastic cells. The unexpected finding of p53-immunoreactive cells in inflammatory lesions, though possibly related to an increased proliferation rate of the basal cell compartment, requires further study and underlines the need for a careful approach to p53 immunocytochemistry. PMID- 8501540 TI - Bcl-2 expression in adult and embryonic non-haematopoietic tissues. AB - The B-cell leukaemia/lymphoma-2 (bcl-2) proto-oncogene is unusual as its product appears to provide survival advantage to B cells by blocking apoptosis. In this study, the expression of bcl-2 has been examined in normal non-haematopoietic tissues, embryos, and psoriatic skin by immunohistochemical staining. Bcl-2 protein expression is mainly observed in cell populations with a long life and/or proliferating ability such as duct cells in exocrine glands, basal keratinocytes, cells at the bottom of colon crypts, and neurons. In the skin of both adult and embryo and also embryonic kidney and cartilage, bcl-2 expression was observed in cells which were undergoing morphological transition from undifferentiated stem cells to committed precursor cells. The finding of bcl-2 expression in the terminal differentiated syncytial trophoblast, but not cytotrophoblast, and in some cells responsive to hormone stimulation such as in the endometrium and myometrium suggests that the gene expression may be related to hormone responsiveness. As no bcl-2 localization was seen in the benign hyperproliferative skin condition psoriasis, this does not suggest a straight forward link to proliferation. These observations support the view that the bcl-2 gene may have an important role in cell development, maturation, and the path to terminal differentiation. PMID- 8501541 TI - Metabolic requirements for phorbol ester-induced cytoskeletal changes in renal epithelium. AB - Alteration of the cytoskeleton and cell-substratum adhesion are important in the progression of renal carcinoma. We have previously shown that treatment of normal human renal epithelium with phorbol esters mimics the changes seen in renal carcinoma cells. In this study we have demonstrated that the phorbol ester induced cytoskeletal reorganization is inhibited in the presence of deoxyglucose but not by cycloheximide. We have also shown that treatment of cells with cytochalasin B results in the formation of immature stress fibres restricted to the cell-substratum contact regions. These results suggest that the actin filaments elongate from the focal contacts and that structural rearrangement caused by phorbol esters is an energy-dependent phenomenon but is independent of de novo protein synthesis. PMID- 8501542 TI - Expression and localization of plasminogen activator inhibitor 1 mRNA in transplant kidneys. AB - Fibrinolysis in renal transplant rejection has not been systematically investigated but is known to be impaired. By an in situ hybridization technique, we have studied gene expression of plasminogen activator inhibitor 1 (PAI-1) in human renal tissue showing severe acute vascular rejection (n = 8), clinically irreversible (chronic) vascular rejection (n = 3), mild vascular rejection (n = 8), parenchymal rejection (n = 4), 'normal' kidneys (n = 6), and non-rejecting kidneys (n = 6). The results showed that in 7/8 cases showing severe acute vascular rejection and in all three chronic vascular rejection cases, PAI-1 mRNA was expressed by endothelial cells of arterioles and arteries, and interstitial inflammatory cells but was not detectable in any other groups. The expression of PAI-1 was frequently associated with areas of haemorrhage. Expression of PAI-1 might be expected to promote thrombosis and ischaemia, the catastrophic consequence of severe vascular rejection. In irreversible chronic rejection, this seems to be the principal mode of action. However, our observation that there is expression of PAI-1 in areas of haemorrhage in severe acute vascular rejection may suggest an additional potentially protective role, if it were produced as a response to haemorrhage. PMID- 8501543 TI - Malignant potential of aneuploid pancreatic endocrine tumours. AB - Evaluation of the malignant potential of pancreatic endocrine tumours is difficult by histological criteria alone. Nuclear deoxyribonucleic acid (DNA) cytometric analysis can provide significant prognostic and biological information in a number of solid human tumours. Thus, the DNA profiles and nuclear parameters of 39 patients with pancreatic endocrine tumours diagnosed from 1969 to 1989 were studied, using computerized video image analysis. Of the 39 patients with tumours, 27 cases did not have evidence of metastatic disease at the time of investigation. The majority of these (N = 21) showed a diploid profile. Five were aneuploid and one was tetraploid. In the 12 tumours that proved malignant, three had tissue of both primary tumour and the metastases analysed; six had material only from the primary tumour, although metastatic disease was established clinically; and another three only had tissue from the secondary tumour studied. The majority of the malignant cases were aneuploid (N = 7); three were diploid; one showed a diploid primary but an aneuploid secondary, and one showed a hyperdiploid pattern. The percentage of nuclei with a DNA content greater than 5N (5CER) did not seem to contribute further to the assessment nor did the means of the nuclear areas and shape factors. It appears that ploidy studies may be useful in predicting malignant potential of pancreatic endocrine tumours. There is a high rate of immunostaining for insulin by benign pancreatic endocrine tumours and this may be a useful adjunct to distinguish them from their malignant counterparts. However, there is no statistically significant correlation between the expression of various hormones and the DNA ploidy of tumour cells. PMID- 8501545 TI - Immunohistochemical detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. PMID- 8501544 TI - Induction of drug-metabolizing enzymes in human pancreatic cancer and chronic pancreatitis. AB - Chronic pancreatitis and pancreatic cancer have both been linked with occupational exposure to organic chemicals. These chemicals are known to be metabolized within the liver by the cytochrome P-450 family of enzymes, and indeed are able to induce levels of these enzymes as evidence of their interaction. The purpose of this study was therefore to see if these enzyme systems were altered in chronic pancreatitis and pancreatic cancer. Immunocytochemistry of four phase I drug-metabolizing enzymes (cytochromes P-450 IIIA1, P-450 IIE, P-450 IA2, and NADPH cytochrome P-450 oxido-reductase) and one phase II enzyme [glutathione S-transferase (GST) 5-5] was therefore performed on pancreas and/or liver biopsy samples from organ donors and compared with patients with chronic pancreatitis or pancreatic cancer. In samples from donor subjects, the types and levels of drug-metabolizing enzymes in hepatocytes were similar to those seen in pancreatic acinar cells. In material from patients with chronic pancreatitis or pancreatic cancer, cytochrome P-450 enzyme levels were greater in both the liver and the pancreas than those seen in the donor group, while GST levels were unchanged. Islets of Langerhans showed high levels of P-450 IA2 in the donor group, with clear induction of P-450 IIIA1 and NADPH cytochrome P-450 oxidoreductase in patients with chronic pancreatitis but not in the pancreatic cancer group. Levels of GST 5-5 were also induced in the islets. The present findings raise the possibility of an aetiological relationship between elevated levels of drug-metabolizing enzymes and the subsequent development of disease. PMID- 8501546 TI - An unusual coronary artery origin in a patient with anomalous left coronary artery. AB - In the typical patient with anomalous left coronary artery (ALCA) arising from the pulmonary artery, the left coronary artery arises from within the left or posterior pulmonary sinus. We report a case of ALCA in which the left coronary arose medially from the pulmonary artery above the commissure separating the right and posterior pulmonary sinuses. This unusual origin highlighted some of the problems with the noninvasive diagnosis of ALCA. PMID- 8501547 TI - Doppler evaluation of central venous lines in the superior vena cava. AB - Thrombus formation in the superior vena cava (SVC) complicates the use of central venous catheters. Visualizing the thrombus by two-dimensional echo-cardiography is often difficult. Flow in the SVC can be recorded by using color flow Doppler examinations. Hence SVC flow was evaluated by color flow Doppler in 12 patients before and within 48 hours of central venous catheters. Five patients with catheters in their SVCs, with suspected thrombus or obstruction to the SVC, were also studied. The SVC flow in the subjects before catheter placement was characterized by two distinct peaks, respiratory variability, and maximal velocities between 0.5 and 1.5 m/sec; these were unchanged by the catheters. The five patients with thrombus or obstruction had turbulent flow, loss of a distinct biphasic profile, and increased velocity downstream to the thrombus and decreased velocity upstream. It appears that Doppler study is a worthwhile adjunct to two dimensional echocardiography in the evaluation of catheter-related thrombus, and that an altered SVC flow profile with increased velocity suggests thrombus formation or obstruction or both. PMID- 8501548 TI - Longevity in congenital heart disease: a tribute to pediatric cardiology. PMID- 8501549 TI - Review of studies evaluating ductal patency in the premature infant. AB - A series of investigations has been performed to assess the timing of physiologic closure of the ductus arteriosus in premature infants with and without respiratory distress syndrome. The data from these studies emphasize the concept of physiologic ductal patency and give normative data for expected closure rates through the fourth day of life. On the basis of these data, patency on or beyond the fourth day of life is abnormal irrespective of gestational age, and prematurity, in the absence of respiratory distress syndrome, is not a risk factor for persistent patent ductus arteriosus. We also found that persistent patent ductus arteriosus in larger premature infants (> or = 30 weeks of gestation) with respiratory distress syndrome is relatively uncommon. Last, ductal patency was evaluated in a group of low birth weight infants with severe respiratory distress syndrome in a randomized, double-blind trial of exogenous surfactant administration. We concluded that the beneficial effects of exogenous surfactant are not associated with either a greater clinical need for indomethacin or any increased risk of delayed closure of the ductus arteriosus. PMID- 8501550 TI - Systemic ventricular size and performance before and after bidirectional cavopulmonary anastomosis. AB - In patients eventually requiring Fontan operation, preoperative ventricular dilation is a risk factor for poor postoperative outcome. Bidirectional cavopulmonary anastomosis (BCPA) has been advocated to reduce ventricular volume load and decrease ventricular dilation; however, this effect has not been documented. To determine the effectiveness of this operation at reducing ventricular size while maintaining ventricular function, we reviewed preoperative and early postoperative echocardiograms in 20 patients undergoing BCPA. Ten of these patients also had later follow-up studies. Ventricular size was assessed by measurement of end-diastolic and end-systolic area, and heart rate was recorded at each study time. Ventricular function was assessed by area shortening. Indexed end-diastolic area was significantly smaller after BCPA than before (26.2 +/- 10.5 vs 21.4 +/- 6.5 cm2/m2). Area shortening and heart rate did not change significantly. Patients who had prior systemic-to-pulmonary shunts had a significant decrease in end-diastolic area after BCPA (30.2 +/- 12.2 vs 22.4 +/- 7.3 cm2/m2); those with prior pulmonary artery banding did not have a significant decrease (22.5 +/- 7.2 vs 19.9 +/- 6.5 cm2/m2). Patients with ventricles having left ventricular morphologic features had a significant decrease in end-diastolic area after BCPA (29.2 +/- 10.8 vs 22.8 +/- 6.5 cm2/m2); those with right ventricular morphologic features did not have a significant decrease (19.2 +/- 5.9 vs 18.0 +/- 5.9 cm2/m2). We conclude that BCPA results in a significantly reduced systemic ventricular preload and size while normal ventricular performance is maintained. Other factors such as prior palliation and ventricular morphologic features may affect the magnitude of the decrease in ventricular size seen after BCPA. PMID- 8501551 TI - Distribution and correlates of creatinine clearance in children and adolescents with blood pressure elevation. AB - The kidney has been implicated as both an etiologic factor and as a target organ in patients with essential hypertension. Renal function has not been studied extensively in children and adolescents with essential hypertension. Eighty-eight subjects, aged 6 to 23 years, with blood pressure persistently above the 90th percentile for age were studied. Creatinine clearance was determined from a single 24-hour urine collection. The mean creatinine clearance was 129.3 +/- 55.3 ml/min per 1.73 m2. Multiple regression analysis was used to investigate potential correlates of creatinine clearance. Because creatinine clearance was not normally distributed, the logarithm of creatinine clearance was used as the dependent variable. Body mass index, resting heart rate, and basal supine plasma renin activity were significant direct independent correlates. Peripheral vascular resistance at maximal exercise was an inverse correlate of the logarithm of creatinine clearance. These findings are consistent with previous studies of adults and may provide the basis for strategies to identify young patients with essential hypertension who are at risk for the development of renal dysfunction. PMID- 8501552 TI - Acute changes in endothelin-1 after hemodialysis for chronic renal failure. AB - Endothelin is a recently described, potent renal vascular and systemic vasoconstrictor peptide. To evaluate the response of this peptide to volume contraction, we measured eight baseline and posthemodialysis samples from seven children, aged 14.5 +/- 3 years, with chronic renal failure. Plasma was extracted and endothelin-1 was measured by radioimmunoassay. Dialysis was performed for a 3 to 3 1/2-hour period, and body weight decreased from 38.0 +/- 14.3 to 36.2 +/- 13.8 kg (p < 0.01) during this time. There were no significant changes in heart rate or respiratory rate after dialysis, but blood pressure fell from 127/80 +/- 22/16 to 114/72 +/- 20/21 mm Hg (p = 0.05 for the systolic pressure). Plasma endothelin-1 concentration increased from 1.5 +/- 1.2 pg/ml at baseline to 7.3 +/ 8.9 pg/ml (p = 0.06) after dialysis; the fall in body weight from dialysis correlated with the increase in endothelin (r = -0.75; p = 0.05). Thus volume contraction from hemodialysis is associated with a rise in plasma endothelin-1, which is related to the acute change in body weight. PMID- 8501553 TI - Developmental differences in cardiac myocyte calcium homeostasis after steady state potassium depolarization: mechanisms and implications for cardioplegia. AB - We previously reported developmental differences in the response of cytosolic free calcium ([Cai]) to extracellular potassium ([Kex]) depolarization (cardioplegia) in juvenile (4 weeks post partum) and mature (12 to 18 months post partum) cardiac myocytes (rabbit). Our present study explored the physiologic basis for these observations. Single calcium-tolerant cardiac myocytes were isolated by sequential exposure to proteolytic agents, loaded with a fluorescent probe for calcium (fura-2) and [Cai] measured by standard fluorescence techniques. The response of [Cai] to [Kex] depolarization (30 mmol/L) was determined in the presence of varying levels of extracellular calcium [Caex], verapamil, ouabain, and amiloride. At nominal levels of [Caex] (0 mmol/L), no significant increases in [Cai] from the juvenile (2.1% +/- 3.3%) or mature (8.5% +/- 3.1%) myocytes were seen. At increasing [Caex], there was a progressive increase in the response of [Cai] to [Kex] depolarization in mature animals' cells (191.8% +/- 40.7%) but not in the juveniles' cells (28.0% +/- 11.5%). Exposure to verapamil resulted in an approximate 80% reduction in relative increase in [Cai] in the mature compared with 60% in the juvenile myocytes. Finally, ouabain exposure resulted in a significant increase in the relative change of [Cai] in juvenile cells (30% to 126.4% +/- 39.4%) but not in the adults' cells. This increase in the juvenile myocytes was blocked by amiloride. We conclude that increases in cardiac myocyte [Cai] after [Kex] depolarization occur predominantly through the calcium channel in the mature animal and through sodium-calcium exchange in the juvenile. PMID- 8501554 TI - Transtelephonic echocardiography: successful use in a tertiary pediatric referral center. AB - Recent advances in computers and telecommunications have made transtelephonic echocardiography practical. Our institution is developing a network of transmissional echocardiographic sites at several hospitals in our referral region. We reviewed our initial experience to determine whether transmissional echocardiographic studies (1) gave an appropriate diagnostic impression compared with subsequent videotape review and (2) led to appropriate clinical management (i.e., transfer to a tertiary center or continuation of local care and follow up). From Aug. 1, 1991, to May 31, 1992, we evaluated 47 transmissional studies (diagnoses: 24 normal, 8 patent ductus arteriosus, 6 ventricular septal defect, 2 pulmonary stenosis, 1 ventricular septal defect with interrupted aortic arch, and 6 miscellaneous). Of 47 studies, 39 (83%) were thought to give accurate diagnostic impressions compared with videotape review. Most inaccuracies were due to the selection and transmission of inconclusive information in an otherwise accurate diagnostic study. Only 1 (2%) of 47 studies resulted in an inappropriate clinical decision; a patient's transfer for treatment of a potent ductus arteriosus was delayed 1 day because of an inconclusive transmissional study. We conclude that transmissional echocardiography is useful in the management of pediatric patients with suspected heart disease in a regional referral setting. PMID- 8501555 TI - Echocardiographic determination of left ventricular preload, afterload, and contractility during and after exercise. AB - Left ventricular (LV) performance increases during acute exercise, but the mechanisms for this increase are not known. To determine the feasibility of studying echocardiographic indexes of performance and its determinants (preload, afterload, and contractility) during exercise, and to examine changes in these indexes, we tested 24 normal male subjects (aged 21 +/- 5 years) by echocardiography--at rest; at 25%, 50%, 75%, and 100% maximal oxygen consumption; and immediately, 3 minutes, and 5 minutes after cycle ergometry. The LV performance (shortening fraction), preload (LV end-diastolic dimension), afterload (wall stress), contractility, heart rate, and peak systolic blood pressure were measured. Data could be obtained during 98% of the exercise studies. The LV performance, heart rate, blood pressure, and contractility increased significantly with increasing exercise, reaching peak levels at maximal exercise, and decreased toward resting levels in the post-exercise period. The LV afterload and preload decreased significantly with increasing exercise intensity, reaching nadir levels at maximal exercise, and increased toward resting levels in the post-exercise period. We conclude that echocardiographic measurement of LV performance and its determinants is feasible during exercise. Performance of the LV increases with increasing exercise intensity because of an associated increase in contractility and decrease in afterload. These data will serve as a basis for comparison with those from other patient populations. PMID- 8501556 TI - Balloon atrial septostomy for left ventricular decompression in patients receiving extracorporeal membrane oxygenation for myocardial failure. AB - We describe the use of balloon atrial septostomy to decompress the left ventricle in four patients receiving extracorporeal membrane oxygenation for acute intractable myocardial failure. These patients were becoming clinically worse and had evidence of left ventricular and left atrial hypertension either by direct measurement or echocardiography. Atrial decompression was accomplished by blade septostomy in one patient and by balloon atrial septostomy under echocardiographic guidance at the bedside in three patients. Three of four patients improved after balloon atrial septostomy and survived. This procedure may be helpful in selected patients receiving extracorporeal membrane oxygenation for myocardial failure with evidence of increased left atrial pressure as a result of increased ventricular pressure. PMID- 8501557 TI - Identifying children at high risk for the development of essential hypertension. AB - BACKGROUND AND OBJECTIVES: Because blood pressure (BP) tracks from childhood to adulthood, some have recommended screening to identify children at high risk for the development of essential hypertension as adults. Others, however, have argued against this strategy because they believe that correlations between childhood and adulthood BP levels are too low. To address these issues, we considered prediction of adult BP from childhood levels. DESIGN: Cohort study with follow-up of participants from childhood to early adulthood. SETTING AND PARTICIPANTS: We ascertained BP in 337 schoolchildren from East Boston, Mass., and reexamined 317 (94%) of them 8 to 12 years later, at ages 18 to 26 years. MEASUREMENTS AND DATA ANALYSIS: On each of several visits, 1 week apart (four for children, three for adults), we obtained three BP readings with a random-zero sphygmomanometer. To calculate correlation coefficients (tracking correlations) between childhood and adult BP, we assumed a multivariate normal distribution and used an iterative maximal likelihood approach in a longitudinal model. We then used these correlations in expressions for sensitivity and specificity of childhood BP as a screening test and for positive predictive value for adult BP above specified cutoff points. RESULTS: During the 8- to 12-year interval, tracking correlations, corrected for within-person variability and adjusted for age, sex, smoking, and medication and alcohol use, were 0.55 for systolic BP and 0.44 for diastolic BP. The corresponding positive predictive values indicated that, for example, the probability that a 20-year-old man's true systolic BP will be > 139 mm Hg (> 90th percentile) was 0.44, given that his observed average systolic BP at age 10 years was > 95th percentile (> 117 mm Hg). The sensitivity of a 10-year old boy's systolic BP > 95th percentile to detect systolic BP > 139 mm Hg 10 years later was 0.17. The specificity of his BP < 95th percentile at age 10 years to detect systolic BP < 139 mm Hg at age 20 years was 0.97. For diastolic BP, predictive values and sensitivities were somewhat lower. CONCLUSIONS: After correction for within-person variability, tracking correlations from childhood to early adulthood are higher than previously reported. However, the resulting sensitivities and predictive values for childhood BP as a screening test for adult BP are of only modest magnitude. These data call into question the usefulness of routine BP measurement to identify children at high risk for the development of essential hypertension. PMID- 8501558 TI - Pediatric infective endocarditis in the modern era. AB - Sixty-two cases of endocarditis occurring in children between January 1977 and February 1992 were reviewed and compared with series from the 1970s and early 1980s. Changes in risk factors, pathogens, diagnostic modalities, and outcome were determined. Complex congenital heart disease (22 cases) and unrepaired ventricular septal defect (9 cases) were the most common underlying lesions. A total of 19 children with normal anatomy had endocarditis; 6 had community acquired infection and 13 had hospital-acquired endocarditis (11 of these 13 children had central venous catheters in place, including 7 premature infants). Echocardiograms revealed vegetations in 25 of 49 patients; 24 of these patients had positive echocardiographic findings on the first study. Echocardiographic findings were most often negative in children with complex cyanotic heart disease. Staphylococcus aureus (39%) was the most common pathogen isolated and was associated with a higher incidence of central nervous system complications (p < 0.0015) and a greater need for surgical intervention (p = 0.01) than were other pathogens. Methicillin-resistant S. aureus (eight cases) and coagulase-negative staphylococci (three cases) emerged as important pathogens but were not associated with increased morbidity or mortality rates. Fungal endocarditis (six cases) had a 67% mortality rate. Overall the mortality rate was 11%. Endocarditis remained undiagnosed in seven seriously ill patients until postmortem examination. This study indicates that, during the past decade, important changes in risk factors, pathogens, and the susceptible population have altered the presentation and management of endocarditis in children. PMID- 8501559 TI - Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. AB - To evaluate the significance of early bacteriologic findings in infants and younger children with cystic fibrosis, we divided patients identified at < or = 2 years of age into groups by initial oropharyngeal culture: group NF, normal respiratory flora (n = 17); group SA, Staphylococcus aureus without Pseudomonas aeruginosa (n = 20); group PA, P. aeruginosa without S. aureus (n = 6); group PA/SA, P. aeruginosa and S. aureus (n = 7); and group O, other potentially pathogenic bacteria (n = 31). Follow-up of patients ranged in age from 5.4 to 13 years. At diagnosis, group PA/SA had lower Brasfield scores (p < 0.02) and higher gamma-globulin levels (p < 0.03) than the other groups. Five years after diagnosis, Brasfield scores were significantly lower in groups PA and PA/SA compared with the other groups; mean gamma-globulin levels did not differ significantly among the groups. Groups PA and PA/SA also had evidence of significantly greater obstructive pulmonary disease by spirometry than groups NF and O. Group PA/SA had a 10-year survival estimate of 57%, significantly lower than the 92% to 100% estimates of the other four groups (p < 0.0001). Thus P. aeruginosa in initial oropharyngeal cultures from patients < or = 2 years of age with cystic fibrosis was associated with significantly increased morbidity, and the finding of P. aeruginosa and S. aureus together in initial oropharyngeal cultures with a significantly increased mortality rate during the first 10 years after diagnosis. PMID- 8501560 TI - Outcome of childhood epilepsy: a population-based study with a simple predictive scoring system for those treated with medication. AB - A population-based study was conducted in an attempt to predict which child's epilepsy will remit. Use of data from a regional electroencephalography laboratory allowed identification of all children in Nova Scotia with epilepsy onset from 1977 through 1985 (excluding those with absence and "minor motor" seizures). Children were followed for an average of 7 years. On the basis of clinical characteristics, a multivariate analysis was used to develop a scoring scheme to predict remission (defined as off medication at the end of the follow up period). Survival curve methods were used to estimate the duration of medication treatment for those with remission. Of the 504 eligible patients, approximately 70% became seizure free long enough to discontinue medication. Approximately 70% of those stopping medication a first time remained seizure free. At the end of follow-up, 55% of the total cohort were in remission. At diagnosis, the best predictors of remission were age < 12 years at onset, normal intelligence, no prior neonatal seizures, and fewer than 21 seizures before treatment. If predicted to have a remission, then, on the basis of survival curve analysis, 80% were without medication 100 months after diagnosis. After 12 months of treatment, prediction was enhanced by including a score for the number of seizures between 6 and 12 months on treatment. We conclude that approximately 55% of childhood epilepsy will remit. Our scoring system predicts reasonably accurately who will have a remission and when medication is likely to be discontinued. PMID- 8501561 TI - Biologic factors as predictors of social outcome of epilepsy in intellectually normal children: a population-based study. AB - We studied social outcome for all the normally intelligent children in our province with onset of epilepsy between 1977 and 1985 (excluding absence and "minor motor" seizures). After follow-up averaging 7 1/2 years, the 337 patients were 7 to 28 years of age. Outcome measures were age dependent. Of those old enough to be at risk, the percentage with each unfavorable outcome was as follows: school failure 34%, use of special educational resources 34%, mental health consultation 22%, psychotropic medication 5%, unemployment 20%, social isolation 27%, inadvertent pregnancy 12%, and criminal conviction 2%. In social isolation 27%, inadvertent pregnancy 12%, and criminal conviction 2%. In a multivariate model correcting for number of potential unfavorable outcomes (based on age at end of follow-up), many variables related to epilepsy, seizure control, and electroencephalographic findings were not associated with social outcome. Only two variables were associated with at least one unfavorable outcome- learning disorder (p < 0.001) and more than 21 seizures before treatment was begun (p < 0.03). The only variable with no unfavorable outcome was simple partial seizures (p < 0.003). Sensitivity and specificity of this model were 54% and 68%, respectively, indicating that social outcome for these children was often not related to biologic factors reflected by the medical details and clinical course of their disorder. PMID- 8501562 TI - Unintentional suffocation by rebreathing: a death scene and physiologic investigation of a possible cause of sudden infant death. AB - As part of a 1-year study of sudden unexpected infant deaths in St. Louis, we performed both a specialized death scene investigation and, in selected cases, a physiologic reconstruction of the death scene with a rabbit model. Those cases in which the infant was found face down with nose and mouth covered by bedding were chosen for the physiologic testing; our goal was to assess the potential for lethal rebreathing of expired air. The physiologic studies reconstructed the infants' premortem ventilatory environment by using the head from an infant mannequin positioned on the actual bedding on which an infant had died and a rabbit breathing through the mannequin's nares. The specialized scene investigation was carried out in 31 of 32 deaths from sudden infant death syndrome, diagnosed by the usual methods. Of 31 infants, eight died with their faces downward and covered by bedding, and the bedding was obtained for further study in seven of eight cases. The bedding had low resistance to airflow (6.25 to 22.6 cm H2O/L per second), and caused considerable rebreathing that was lethal to the rabbits in five of seven cases. We conclude that items of bedding in common use are capable of causing lethal rebreathing by prone-sleeping infants whose nose and mouth become covered; suffocation by rebreathing was the probable mechanism of death in a substantial number of these deaths that had been attributed to sudden infant death syndrome. PMID- 8501563 TI - Upper airway resistance in infants at risk for sudden infant death syndrome. AB - To investigate the relationship between sudden infant death syndrome and upper airway obstruction, we studied 14 term infants at a mean age of 11 weeks who had been identified as being at risk for sudden infant death syndrome on the basis of clinical and family histories and polygraphic monitoring. Respiratory efforts during sleep were investigated by esophageal pressure monitoring (all 14 infants) and by monitoring of flow with a pneumotachometer (6 infants). During apparently normal sleep, increased respiratory efforts were shown by intermittent increases in the magnitude of the negativity of esophageal pressure. Mild changes in tidal volume occurred occasionally, always at the lowest monitored esophageal pressure of a breath sequence. These tidal volume decreases had no impact on oxygen saturation but led to a short arousal and decreased respiratory efforts, followed by a return to normal breathing. Occasionally the abnormal increase in upper airway resistance did not lead to an immediate arousal but instead to a short obstructive apnea that was then followed by an arousal. This investigation indicates the importance of arousal mechanisms in maintaining normal breathing during sleep. Any disruption of the arousal mechanisms during sleep (including sleep fragmentation caused by repetitive arousals) may place these infants with increased upper airway resistance at risk for obstructive apnea during sleep. PMID- 8501564 TI - Health of very low birth weight children during their first eight years. AB - To determine the impact of very low birth weight (VLBW) on medical outcomes during childhood, we compared the health of 249 VLBW children born from 1977 through 1979 with that of 363 normal birth weight (NBW) control children at 8 years of age. Measures included the rates of specific illnesses, surgical procedures and accidents, growth, and other physical findings. The number of medical conditions and surgical procedures was significantly greater in the VLBW children than in the NBW control children. Eighteen percent of VLBW versus 5% of NBW children had had respiratory conditions (p < 0.001), mainly before 3 years of age. Surgical procedures were more common both before and after 3 years of age, but accidents occurred with similar frequency. The VLBW children had significantly lower weight, height, and head circumference and more minor physical stigmata. Thus medical illness, surgical interventions, and poor growth attainment are part of the ongoing morbidity of VLBW children during childhood. PMID- 8501565 TI - Congenital diaphragmatic hernia: long-term outcome in neonates treated with extracorporeal membrane oxygenation. AB - As more infants with congenital diaphragmatic hernia (CDH) survive with extracorporeal membrane oxygenation (ECMO), it seems prudent to detail the longterm outcome in these medically complex infants. Eighteen children with CDH treated with postoperative ECMO were recruited for participation in this study. The mean duration of ECMO was 193 hours (range 82 to 493 hours), mean time to extubation after ECMO was 142 hours (range 34 to 312 hours), and median duration of hospitalization was 46 days (range 30 to 181 days). Of the 18 infants, 4 (22%) were discharged home requiring oxygen therapy. At follow-up the notable findings were a high incidence of gastroesophageal reflux and failure to thrive. At both 1 and 2 years of age, 50% of infants were at less than the 5th percentile for weight. At 1 and 2 years of age, 39% and 21%, respectively, were at less than the 5th percentile for weight/length ratio. A total of 16 children (89%) had clinical evidence of reflux, and 8 (44%) were discharged home on a regimen of nasogastric feedings. Reherniation occurred in 4 children (22%) and was more frequent when a patch was used. An electrocardiogram showed right ventricular hypertrophy in 6 (43%); oxygen saturation by pulse oximetry was > 95% in all children, and pulmonary artery pressure was estimated by Doppler echocardiography to be normal in 12 of 14 children examined. The neurodevelopmental outcome (Bayley Scales or Stanford-Binet scale) at 1 to 4 years of age was not dissimilar from that of other ECMO-treated children. Given the severity of illness in the neonatal period, the general health and development of children with CDH surviving after ECMO are good. Surprisingly few children have long-term respiratory complications related to pulmonary hypoplasia. Follow-up in the first few years should be aimed at aggressive nutritional intervention to prevent the growth failure that appears to be prevalent in these children. PMID- 8501566 TI - Pertussis immunization and characteristics related to first seizures in infants and children. AB - In a previous study in which we examined the relationship of pertussis immunization to the onset of neurologic disorders during 1967 and 1968 and during 1972 and 1973 in Denmark, there were 554 children with initial onset of epilepsy and 2158 children with first febrile convulsions. In the study population there were 112 children with epilepsy and 229 children with febrile convulsions for whom the exact date of pertussis immunization and the exact date of the onset of illness were known. We analyzed selected clinical variables by specific time intervals between pertussis immunization and the first seizure. In the children with epilepsy, no relationship was found between time of pertussis immunization and the specific variables that were examined. In contrast, the following characteristics in children with febrile seizures were significantly more common when pertussis immunization had occurred within 3 days, compared with more than 7 days of the event: first seizure more than 10 minutes in duration, the occurrence of more than one seizure, the longest seizure (when there was more than one) more than 10 minutes in duration, and the occurrence of a seizure described as focal. The lack of specific characteristics in epilepsy that had its onset in a temporal relationship to pertussis immunization is further evidence that pertussis vaccine does not cause this disorder. The cause of increased severity of febrile seizures apparently associated with pertussis immunization is unknown. PMID- 8501567 TI - Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate. AB - In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4 months of age and the standard Schwarz vaccine from 9 months of age. Children were followed to the age of at least 3 years. The mortality ratio of the EZ vaccinees compared with control subjects was 1.79 (range, 1.06 to 3.02; p = 0.027) if children were excluded at the time of migration; if deaths after migration were included, the mortality ratio was 1.53 (range, 0.94 to 2.49; p = 0.087). Girls in the EZ group had significantly higher mortality rates than girls in the control group (mortality ratio = 1.95; range, 1.07 to 3.56; p = 0.027); there was no difference for the boys (mortality ratio = 0.98; range, 0.41 to 2.30). Adjustment for background factors in a Cox regression model did not modify these estimates. Furthermore, female recipients of EZ vaccine had more days with diarrhea (relative risk = 1.35; range, 1.17 to 1.56; p = 0.00003) and were more likely than control subjects to visit a health center in the month after vaccination (relative risk = 1.86; range, 1.05 to 3.31; p = 0.027); those who consulted were more likely to die subsequently (mortality ratio = 2.31; range, 0.99 to 5.41; p = 0.054). These observations were unplanned and require confirmation in larger studies. PMID- 8501568 TI - Early severe infantile botulism. AB - Two neonates with a history of diarrhea, abrupt apnea, and suspected sepsis were proved to have infantile botulism. Initial symptoms in both infants suggested other diagnoses. Electrophysiologic studies were important in confirming the diagnosis. Early severe infantile botulism may be rare but should be considered in neonates who have hypotonia and respiratory arrest or a sepsis-like clinical picture. PMID- 8501569 TI - Serial measurements of neuropeptide Y in plasma for monitoring neuroblastoma in children. AB - Neuropeptide Y (NPY) was studied as a marker for neuroblastoma in 12 children. All but one patient with neuroblastoma had elevated plasma NPY concentrations at diagnosis. During treatment NPY values returned to normal in 9 of 12 children. All three children without normalization of plasma NPY values died; two of them had a relapse and the third died of toxic effects. Plasma NPY appears to be a sensitive marker of neuroblastoma. PMID- 8501570 TI - Recurrent metabolic decompensation in profound carnitine palmitoyltransferase II deficiency. AB - A 3-year-old boy had recurrent episodes of lethargy, encephalopathy, and hepatomegaly accompanied by hypoglycemia, elevated liver aminotransferase and creatine kinase values, and nonketotic dicarboxylic aciduria; the serum carnitine level was moderately reduced. Carnitine palmitoyltransferase II activity was decreased in lymphocytes and fibroblasts. Therapy with L-carnitine and a diet low in long-chain triglycerides did not prevent recurrent episodes. PMID- 8501571 TI - Diarrheal deaths in children living in New Mexico: toward a strategy of preventive interventions. AB - We reviewed 26 childhood diarrheal deaths examined by the New Mexico Office of the Medical Investigator, from 1980 through 1989, to identify circumstances surrounding the illness that might lead to strategies for prevention. Children who died were younger than 9 months of age (88%) and were from minority groups (American Indian 54%, Hispanic 23%); 12 (46%) had seen a physician within 3 days of death. Interventions to avert these deaths include educating parents to seek earlier treatment and health care providers to recognize that acutely dehydrating diarrhea can be fatal. PMID- 8501572 TI - Increased energy expenditure in a patient with diencephalic syndrome. AB - Total energy expenditure, measured in an infant with diencephalic syndrome with doubly labeled water, was 30% to 50% higher than that reported for other healthy infants whose energy expenditure was measured by the same technique and 13% higher than the patient's energy intake. This result suggests that the weight loss and cachexia of the diencephalic syndrome are the result of abnormally increased energy expenditure. PMID- 8501573 TI - Abnormalities of the corrected QT interval in familial dysautonomia: an indicator of autonomic dysfunction. AB - We report abnormalities in corrected QT intervals with changes in position and after exercise in patients with familial dysautonomia and confirm the previously reported finding of abnormal heart rate and blood pressure responses. Prolonged corrected QT intervals (> 440 msec) with lack of appropriate shortening with exercise is a noninvasive means of demonstrating an aberration in autonomic regulation of cardiac conduction. PMID- 8501575 TI - Transient myocardial ischemia in infants prenatally exposed to cocaine. AB - This prospective study examined whether neonates of pregnant women who used cocaine during pregnancy are at a risk for the development of transient myocardial ischemia and altered autonomic function, as in adults. We studied 21 of 35 infants with a history of prenatal exposure to cocaine. The ST segment changes and heart rate variability were evaluated from three-channel Holter monitors within 48 hours of birth. The data were compared with those on 20 control infants with similar birth weight, gestational age, and postnatal age. Six infants (29%) who were exposed to cocaine in utero had transient ST segment elevation, versus only one infant (5%) from the control group (odds ratio = 7.6; 95% confidence interval, 1.14, 50.64). Heart rates, results of total power and low-frequency power spectral analyses for heart rate variability, and arrhythmias were not significantly different in the two groups. However, a lower ratio of low to high-frequency power reflected increased vagal activity in cocaine-exposed infants. We conclude that cocaine use in pregnant mothers is associated with transient ST segment abnormalities in their infants. These abnormalities are consistent with transient myocardial ischemia. PMID- 8501574 TI - Comparison of group B streptococcal hyperimmune globulin and standard intravenously administered immune globulin in neonates. AB - Standard intravenously administered immune globulin (IVIG) contains varying amounts of group B streptococcus (GBS) antibody. A GBS hyperimmune IVIG was produced by immunizing plasma donors. The GBS type-specific opsonic activity was > or = 90% in the hyperimmune IVIG at a 1280 dilution-1 versus at a 10 dilution-1 in standard IVIG. Suckling rat survival after GBS type-specific infection was 100% when the rats were treated with hyperimmune IVIG versus < or = 20% with standard IVIG. To evaluate the effect of this product on GBS antibody levels and clinical toxic effects, we randomly administered either GBS hyperimmune IVIG, 500, 250, or 100 mg/kg, or standard IVIG, 500 mg/kg, to 20 neonates with suspected sepsis. No adverse effects were observed. Total and subclass serum IgG levels reflected only the dose; serum GBS type-specific IgG and opsonic activity reflected both the product and dose of IVIG administered. Standard IVIG did not significantly increase serum GBS type-specific IgG, whereas hyperimmune IVIG, 500 mg/kg, produced a fourfold rise for > 6 weeks; more variable increases were observed after 250 and 100 mg/kg doses were given. Serum GBS type-specific opsonic activity correlated with serum GBS type-specific IgG levels (R2 = 0.74; p < 0.0001). Further studies of this or similar products will be necessary to determine whether GBS type-specific antibody improves the outcome of GBS-infected neonates. PMID- 8501576 TI - Effects of venovenous extracorporeal membrane oxygenation on cardiac performance as determined by echocardiographic measurements. AB - We evaluated the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cardiac performance by echocardiographic measurements in 15 infants. Heart rate and blood pressure were also recorded. Echocardiographic measurements included aortic and pulmonary peak blood flow velocities, pulmonary time to peak velocity, left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, and peak systolic wall stress before, during, and after venovenous ECMO. Pre-ECMO echocardiograms showed borderline or normal indexes of cardiac function. After initiation of venovenous ECMO, all infants had normalization and no infant had deterioration of cardiac performance. The inotropic agents dopamine and dobutamine were decreased from average doses of 12 and 3.6 micrograms/kg per minute, respectively, to 3.7 and 1.3 micrograms/kg per minute, respectively, within 8.8 hours of the institution of venovenous ECMO. During this time the mean arterial pressure remained stable, and the heart rate decreased (169 +/- 21 vs 136 +/- 15 beats/min; p < 0.001). During the course of ECMO there were no changes in left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, or aortic peak blood flow velocities. Pulmonary artery peak blood flow velocity (69 +/- 22 vs 92 +/- 28 cm/sec; p = 0.04) and pulmonary time to peak velocity improved (47 +/- 11 vs 65 +/- 16 msec; p = 0.026). We conclude that venovenous ECMO does not have deleterious effects on cardiac performance. PMID- 8501578 TI - Fibrin glue treatment of persistent pneumothorax in a premature infant. AB - Fibrin glue pleurodesis has been used to treat bronchopleural fistulas in adults. We report the successful use of fibrin glue in a premature infant to seal a pneumothorax that had persisted for more than 3 weeks despite high-frequency ventilation. PMID- 8501577 TI - Toxic reaction to salicylate in a newborn infant: similarities to neonatal sepsis. AB - A newborn infant had metabolic acidosis, tachypnea, and hypoglycemia. After the initial diagnosis of neonatal sepsis, she was given antibiotics but failed to respond. Further investigation revealed that her mother had taken aspirin throughout pregnancy. This case illustrates the similarities between symptoms of neonatal sepsis and those of a toxic reaction to salicylate. PMID- 8501579 TI - Randomized study of two doses of didanosine in children infected with human immunodeficiency virus. AB - 2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability. PMID- 8501580 TI - Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome. AB - The pharmacokinetics and safety of HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 +/- 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 +/- 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 +/- 6.8 hours) and plasma concentration after infusion (30.7 +/- 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponential function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 +/- 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 +/- 0.02 L/kg) were different (p < 0.002) from values observed in children's blood samples during 36 hours. Within the pediatric population, no age-related differences in pharmacokinetics could be detected. Drug disposition was unaffected by renal or hepatic dysfunction. Decreased blood pressure was the most frequently reported adverse event; 4 (9%) episodes in 44 infusions were considered possibly related to the study drug. Gram negative bacteremia was documented in 23 (55%) of 42 patients. The overall mortality rate was 31%. Enterobacter cloacae was the most common pathogen isolated. Haemophilus influenzae type b was isolated from one child with sepsis syndrome. We conclude that infusion of HA-1A in children is associated with a low incidence of side effects. The pharmacokinetic-pharmacodynamic behavior of HA-1A in children requires further study to determine whether developmental differences exist and how these differences might affect drug administration. Efficacy remains to be studied. PMID- 8501581 TI - Spontaneous hemorrhage associated with accidental brodifacoum poisoning in a child. AB - A 36-month-old child had spontaneous hemorrhage from her nose, mouth, and urinary tract, and a fall in hemoglobin of 20 gm/L (2 gm/dl). The prothrombin time and partial thromboplastin time were markedly prolonged with a decrease in the vitamin K-dependent factors. The child had ingested brodifacoum, a long-acting rodenticide. Prolonged follow-up and treatment with vitamin K were necessary. PMID- 8501582 TI - Recent advances in cystic fibrosis research. AB - After the discovery of the gene, the next major landmark will be the elucidation of the basic defect of the disorder, which should lead to rational treatments. The accumulating knowledge of mutations and phenotypes allows more accurate testing and screening in selected populations. Considerable information is now available both on the pattern of gene and protein expression in the tissues involved in the disease and on the complex regulation and function of CFTR. In addition, an animal model with which to test therapeutic strategies has become available. Finally, two potential ways to cure the disease have emerged: that which exploits our knowledge of the normal and the mutant protein and their function, and that based on gene therapy. The latter approach is probably beginning to be tested on small groups of patients, and proof of its effectiveness is eagerly awaited. PMID- 8501583 TI - Descriptions of dietary assessment methods. PMID- 8501584 TI - Cytokines and lymphocyte function in children infected with human immunodeficiency virus. PMID- 8501585 TI - Linoleic acid in mature milk from Israeli mothers. PMID- 8501586 TI - Neutrophil counts in newborn infants at high altitude. PMID- 8501587 TI - Criteria for publication of case reports. PMID- 8501588 TI - Characteristics of phenol oxidase of Schistosoma mansoni and its functional implications in eggshell synthesis. AB - It is proposed that the phenol oxidase enzyme of schistosomes and other trematodes has a crucial role in the cross-linking of precursor proteins in the formation of the eggshell. However, to date there is no direct evidence to show that the enzyme catalyzes the reactions necessary for the posttranslational modification of eggshell precursor proteins. In this report we demonstrate that an eggshell precursor protein acts as a substrate for a schistosome fraction that catalyzed the 2 steps in the oxidation of tyrosine. This action of the phenol oxidase-containing worm fraction resulted in the tyrosine-dependent insolubilization and aggregation of the protein, suggesting a role for the enzyme in the posttranslational modification and cross-linking of schistosome eggshell proteins. The enzyme-rich fraction from Schistosoma mansoni catalyzed both steps of the reactions necessary for the conversion of tyrosine residues on putative eggshell precursor protein (p48) to quinones. The parasite fraction also catalyzed the hydroxylation of free L-tyrosine to DOPA (monophenol oxidase activity) and the oxidation of L-DOPA to dopaquinone (diphenol oxidase activity). Both activities of the enzyme are avidly bound to membranous structures, are susceptible to agents known to inhibit a functionally related enzyme, tyrosinase, and may reside on the same protein. PMID- 8501589 TI - Hematozoa from passeriform birds in Louisiana. AB - Blood smears were examined from 935 individuals of 19 migrant and resident bird species collected in Louisiana. Of these, 320 (34.2%) harbored hematozoa. The prevalences of parasites were as follows: Haemoproteus spp. 22.8%, Trypanosoma spp. 6.9%, unidentified microfilariae 5.0%, Plasmodium spp. 3.4%, and Leucocytozoon spp. 1.3%. These data are consistent with other reports from the region. Infections were observed in 33% of the individuals in the 13 migrant species sampled and 33% of the individuals in the 6 resident species. PMID- 8501590 TI - Biochemical, biological, and genetic characterization of a sylvatic isolate of Trichinella. AB - Biological, biochemical, and genetic relationships of Trichinella isolates were assessed and compared from 3 species of Illinois fur-bearing mammals. Tongue muscle collected from 1987 through 1989 from 323 raccoons (Procyon lotor), 9 red fox (Vulpes fulva), and 1 coyote (Canis latrans) were digested and Trichinella muscle larval prevalences and mean intensities (larvae/g) determined. The prevalence and mean intensity of tongue muscle-stage larvae were 2.8% and 44.4% and 326 and 2 larvae/g for raccoon and red fox, respectively. The single coyote examined for muscle larvae was negative. Seven of 13 Trichinella isolates (5 raccoon, 2 red fox) were maintained and amplified in mice. Comparative analyses of DNA from larvae of these isolates and from other Trichinella isolates were performed by dot-blot hybridization using specific repetitive DNA probes. DNA from the 7 Illinois sylvatic isolates reacted with the Trichinella T5 isolate DNA probe pUPB-3.7 and did not cross-react with the Trichinella spiralis probe pBP-2. The sylvatic isolates of Trichinella were also analyzed using 27 allozymes. Their allozymic patterns were similar to Trichinella reference strain T5 from Pennsylvania, except for mannose phosphate isomerase. These results suggest that the Illinois wildlife isolates belong to the Trichinella T5 genotype according to the classification system established by the International Trichinella Reference Centre and as defined here by positive hybridization to the pUPB-3.7 probe. Results from Southern blot analyses using rRNA as a probe and allozyme patterns revealed some heterogeneity among geographical isolates of the T5 genotype. PMID- 8501591 TI - Blood parasites of amphibians from Sichuan Province, People's Republic of China. AB - Two hundred forty-six amphibians from Sichuan Province, People's Republic of China, were examined for blood parasites between April and June 1990. Six trypanosome species were found, 2 of which were not identified because of poor material. Trypanosoma rotatorium (sensu Mayer, 1843) was found in Rana limnocharis and Rana nigromaculata. Trypanosoma chattoni and a T. rotatorium-like species were found in Bufo gargarizans. A sphaeromastigote similar to Trypanosoma tsunezomiyatai was seen in R. limnocharis. The relationship of this parasite to T. chattoni is unclear. Dactylosoma ranarum, Lankesterella minima, and Aegyptianella bacterifera were identified in ranids. Frog erythrocytic virus (FEV) was found in 2 ranids and a bufonid. Differences in shape of FEV and its assumed effect on the host-cell nucleus suggest that different kinds of viruses may be involved. PMID- 8501592 TI - Effects of dehydroepiandrosterone in immunosuppressed rats infected with Cryptosporidium parvum. AB - Cryptosporidium parvum is a coccidian parasite that causes diarrheal disease in animals and humans. Severe cryptosporidial infections were noted in young adult rats immunosuppressed with the glucocorticosteroid dexamethasone (DEX). B-cell and T-cell responses to the mitogens lipopolysaccharide and concanavalin A, respectively, were depressed in the DEX-treated rats. In addition, DEX treatment suppressed serum IgG levels, in vitro IgG production, and natural killer cell activities. Previous results have shown that DEX-immunosuppressed rats treated with dehydroepiandrosterone (DHEA) exhibit significant reductions in cryptosporidiosis as determined by monitoring oocyst shedding in the feces and parasite colonization of the small intestine. Results from this study indicated that B- and T-cell responses to their respective mitogens, serum IgG levels, and in vitro IgG production were greater in DHEA-treated immunosuppressed rats than in untreated DEX-immunosuppressed rats infected with C. parvum. Similar results were demonstrated in DHEA-treated versus normal control rats infected with C. parvum. These results suggest that the effects of DHEA in reducing cryptosporidiosis are the result of a potentiation of the immune system in the immunosuppressed rats. PMID- 8501593 TI - Persistence of a recurrent group of intestinal helminth species in a coyote population from southern Texas. AB - The persistence and interrelationships of a recurrent group of intestinal helminth species in a coyote population from southern Texas were determined; data were collected at 4-yr intervals (1979, 1983, and 1987). The a priori expectation was that a defined recurrent group of helminth species persisted over time and that the respective helminth species were stable in terms of their abundances. The Fager index and subsequent recurrent group analysis indicated a small group of taxonomically unrelated recurring species of helminths that always demonstrated affinities with each other and occasionally with certain of the remaining species. Although there were differences across host subpopulations delineated by sex and age, temporal changes reflective of extrinsic environmental variables acting on certain helminth species appeared to have the greatest effect on recurrent group size and structure. Three of the 8 common intestinal helminth species (Ancylostoma caninum, Oncicola canis, and Alaria marcianae) occurred in all recurrent groups. Thus, there was temporal persistence of a small recurrent group of dominant helminth species that formed the basis of the intestinal helminth community in this coyote population. PMID- 8501594 TI - Diphyllobothrium dendriticum and Diphyllobothrium latum in fishes from southern Argentina: association, abundance, distribution, pathological effects, and risk of human infection. AB - Diphyllobothrium dendriticum and Diphyllobothrium latum are reported for the first time from Argentina. The following species from Lake Moreno (southern Argentina) were studied to determine whether plerocercoids were present: 11 brook trout (Salvelinus fontinalis), 32 perca (Percichthys sp.), 21 pejerrey (Patagonina hatcheri), and 114 rainbow trout (Oncorhynchus mykiss). Brook trout harbored both species (27.3% prevalence of D. dendriticum and 9.0% of D. latum); perca harbored only D. latum (18.7% prevalence); pejerrey were not infected and rainbow trout also harbored both species, with significant association. Diphyllobothrium latum was less abundant (1.4 plerocercoids/fish, 28.0% prevalence) than D. dendriticum (7.2 plerocercoids/fish, 57.8% prevalence) implying a lower health risk for humans. For both parasites, rainbow trout seem to be more important than the other host species studied. There is no evidence that either of the species is more harmful to the host. The lack of significant weight variation of the liver as related to intensity of infection strongly suggests that competition for energy is not an important aspect of the host pathology. PMID- 8501595 TI - Thymus-related cellular immune mechanisms in sex-associated resistance to experimental murine cysticercosis (Taenia crassiceps). AB - The role of sex, thymus, and cellular immune mechanisms in mouse resistance to experimental cysticercosis with Taenia crassiceps was studied in male and female susceptible mice treated with cyclophosphamide, as well as in mice neonatally thymectomized and passively transferred with T-enriched lymphoid cells. High doses of cyclophosphamide increased delayed hypersensitivity and resistance of mice of both sexes without affecting antibody production. Neonatal thymectomy diminished resistance in both sexes but depressed delayed hypersensitivity in females only, without significantly affecting antibody response in either sex. Passive transfer of T-enriched lymphoid cells to thymectomized mice restored resistance to control levels without greatly affecting delayed hypersensitivity. Thus, our results indicate that cell-associated immune mechanisms are implicated in resistance to murine cysticercosis with T. crassiceps. Because neonatal thymectomy nearly equalized the intensity of infection of female and male mice, it is argued that the thymus is importantly involved in the interaction between gonads and the immune system in the control of this cysticercosis. PMID- 8501596 TI - Growth and development of Brugia pahangi larvae under various in vitro conditions. AB - In vitro culture methods were utilized to investigate specific nutritional requirements of Brugia pahangi larvae. Infective third-stage larvae (L3) isolated from Aedes aegypti (Liverpool) mosquitoes were cultured in NCTC 135:IMDM (NI) medium plus various types of serum under 5% CO2/air and 5% CO2/N2 atmospheres. Larvae grew, developed, and molted to the fourth stage (L4); however, further growth and differentiation beyond the mid-L4 were minimal. Serum supplementation was necessary to induce molting of B. pahangi L3s. Iron-supplemented calf serum (FeCS) consistently promoted higher percentages of molting than the other 4 types of serum tested. Specific nutritional requirements for B. pahangi larvae were assessed through testing of supplements known to be important for growth of mammalian cells or other parasites in vitro. Addition of various concentrations and combinations of hemoglobin, insulin, transferrin, selenium, albumin, cholesterol, or a cell feeder layer did not improve larval growth, molting, or survival compared to that obtained with FeCS alone. The L4s derived from in vitro culture, when injected intraperitoneally into jirds, developed to sexually mature, microfilarial-producing adults in a normal in vivo time frame. Developing L4s isolated from jirds molted to young adults in vitro in NI medium plus serum. PMID- 8501597 TI - Selection for a strain of Haemonchus contortus that exhibits periparturient egg rise in sheep. AB - Periparturient egg rise (PPR) is a principal means for some nematode parasites to survive over winter and to provide transmission of infective larvae from ewes to lambs during the spring. Routine laboratory propagation techniques probably have selected for those characteristics that would not promote PPR in conventional laboratory strains of Haemonchus contortus. An established isolate of H. contortus (BPL) was the source of the initial inoculum to select for a strain that readily exhibits characteristics of PPR. The selection process included inoculation of helminth-free pregnant ewes during mid-gestation, collection of nematode eggs during lactation, and storage of infective larvae at 4 C for 4 mo. After 10 generations, the 2 strains, BPL and PPR from lambs and pregnant ewes were compared for reproductive, morphological, and population differences in lambs and pregnant ewes. After lambing, ewes inoculated with the PPR strain had significantly higher fecal egg concentrations. Lambs inoculated with the PPR strain had higher egg concentrations, higher total daily egg production, fewer adult worms, larger female worms, and higher fecundity. Repeated selection in the appropriate host, after prolonged storage of the inoculum, produced a PPR strain of H. contortus morphologically and reproductively distinct from the initial source isolate. PMID- 8501598 TI - Arrested development in a freshwater myxosporean, Myxidium salvelini, following transfer of its host, the sockeye salmon (Oncorhynchus nerka), to sea water. AB - The duration of infections with Myxidium salvelini, a freshwater myxosporean, in the kidneys of anadromous sockeye salmon (Oncorhynchus nerka) smolts from Cultus Lake, Fraser River system, British Columbia, was followed both in fresh water (FW) and in sea water (SW). The smolts were collected at the outlet of the lake as they migrated seaward, were subsequently held captive in M. salvelini-free FW or SW, and were sampled for presence of the parasite biweekly. Initial prevalence of infection was 80% or higher. In FW-held fish, spores were detectable over the 28-wk period of sampling, but the prevalence of infection with spores and prespore forms declined sharply after 22 wk. Nine weeks after the fish were transferred to SW, spores no longer were present but prespore forms continued to be present at high prevalences for up to 25 wk. SW-held fish were reacclimated to FW 4 wk after the last detection of spores. Spore production was resumed in this group of fish within 8 wk and continued for the next 5 wk, when the study was terminated. This indicates that M. salvelini persisted in an arrested prespore form during the SW holding period. This is the first report of arrested development in a prespore stage of a myxosporean. The physiological changes in the kidney that accompany migration of anadromous salmon from fresh to sea water likely inhibit spore production in M. salvelini. In FW salmonids, M. salvelini appears to have an annual life cycle. PMID- 8501599 TI - Relationships of Trichomonas gallinae to the palatal-esophageal junction of ring doves (Streptopelia risoria) as revealed by scanning electron microscopy. AB - Ring doves (Streptopelia risoria) were experimentally infected with pathogenic (virulent) Trichomonas gallinae so that trichomonad activities in the upper alimentary tract, prior to canker formation, could be examined with scanning electron microscopy. Between 6 and 15 hr postinoculation low numbers of ameboid T. gallinae were attached to apical microfolds and cell borders of the palatal esophageal junction squamous epithelium. Initial parasite activities at tightly attached cell borders and apical microfolds suggest that some parasite-secreted factor or factors initiated squamous cell damage, separation, and removal. As squamous cell borders separated, trichomonads invaded areas beneath them and ultimately aided in their complete removal. Accelerated parasite-mediated desquamation, the invasion of increased mucosal surface area by trichomonads, and the eruption and expansion of cankers were the primary changes to the palatal esophageal junction and other upper alimentary tract tissues that occurred between 19 and 240 hr postinoculation. PMID- 8501600 TI - Production of heterogeneous carbohydrate-binding proteins by the host snail Biomphalaria glabrata following exposure to Echinostoma paraensei and Schistosoma mansoni. AB - Hemolymph lectins may play an important role in the internal defense responses of gastropods to parasites. Two groups of known carbohydrate-binding polypeptides, of 150-220 kDa (designated as group 1 molecules, or G1M) and of 75-130 kDa (group 2 molecules, or G2M), were harvested from pooled plasma samples of Biomphalaria glabrata using affinity chromatography and examined using 2-dimensional electrophoresis. Plasma samples were derived from control snails or snails exposed 8 days earlier to the trematodes Echinostoma paraensei or Schistosoma mansoni. Plasma of control and S. mansoni-exposed snails contained little or no G1M, whereas plasma from E. paraensei-infected snails contained G1M covering a broad pI spectrum. G2M resolved as 1-2 isoforms in control plasma and up to 4 relatively faint isoforms in plasma from S. mansoni-exposed snails, and as 5-6 resolvable isoforms in plasma from E. paraensei-infected snails. Plasma from individual snails contained as many as 5 G2M polypeptides following exposure to E. paraensei. Exposure to trematode larvae stimulated production by B. glabrata of increased abundance and diversity of carbohydrate-binding proteins. The 2 trematode species provoked different responses, and 2 B. glabrata strains studied (M line and 13-16-R1 strains) differed from one another in their responses. PMID- 8501601 TI - Ultrastructural characteristics of Babesia odocoilei in vitro. AB - Babesia odocoilei continuously cultured in white-tailed deer (Odocoileus virginianus) erythrocytes was examined by transmission and scanning electron microscopy. Merozoites, trophozoites, intermediate-stage forms, and dividing forms were observed. Merozoites possessed a single nucleus, inner membrane complex, rhoptries, free ribosomes, rough endoplasmic reticulum, and single membrane-bound vesicles. Trophozoites lacked an inner membrane complex and rhoptries. Intermediate stages were characterized by distinct segments of inner membrane complex. Dividing forms ranged from cells with an elongated nucleus to mature daughter cells joined by a ringlike structure. Babesia odocoilei was characterized by its close proximity to the erythrocyte membrane, membranous structures resembling feeding organelles, and reproduction via a method resembling budding sensu stricto. PMID- 8501602 TI - The niche of the gill parasite Dactylogyrus banghami (Monogenea: Dactylogyridae) on Notropis stramineus (Pisces: Cyprinidae). AB - Distribution of the monogenean Dactylogyrus banghami on the gills of the fish Notropis stramineus (Cyprinidae) was described by calculation of mean relative positions and Levins' niche breadths on the linear spatial resource gradients gill filament length and gill arch length. Thirty fish with 276 worms were examined; only 1 of the fish had an additional gill parasite species (Trichodina sp). Worms were more broadly and evenly distributed across the length of the gill arch than they were on the filament (breadths of 0.91 and 0.67, respectively). Mean worm positions were near the center of both resources: 54% of the distance from the arch cartilage on the filament, and 54% from the ventral end of the arch itself. The results are considered consistent with predictions about the niche structures of species in unsaturated noninteractive specialist communities. PMID- 8501604 TI - Nematode larvae in fossilized animal coprolites from lower and middle Pleistocene sites, central Italy. AB - Nematode larvae were found in mineralized animal coprolites collected in lower and middle Pleistocene sites, central Italy. Coprolites collected in 4 paleontological sites dated from 1.5 million years to 30,000 years ago were identified as of Hyaenidae (Mammalia, Carnivora). Checklists available for present-day Hyaenidae did not permit identification of the larvae found. This is one of the most ancient parasite findings in coprolites. PMID- 8501603 TI - Arbitrarily primed polymerase chain reaction of individual Trichinella specimens. AB - Recently, 5 sibling species and 3 other phenotypes were identified in the genus Trichinella. Single primers of arbitrary nucleotide sequence were used to produce random amplified polymorphic DNA starting from decreasing amounts of Trichinella spiralis and Trichinella britovi DNA. Reproducible amplification products from 30 pg of DNA were obtained using 1 of 6 examined primers. These fragments distinguish between 2 European Trichinella species, T. spiralis, showing a 1,350 bp band, and T. britovi, showing 400- and 1,100-bp bands. The developed procedure allows the characterization of crude DNA preparations of single muscle-stage larvae, avoiding time-consuming passages of parasites in laboratory animals. PMID- 8501605 TI - Penetration of Schistosoma mansoni cercariae into a living skin equivalent. AB - We evaluated the use of a living skin equivalent (LSE) as a suitable membrane for Schistosoma mansoni cercarial penetration. LSE is a living artificial skin composed of a dermal layer containing human dermal fibroblasts embedded in a collagen lattice and an epidermal layer consisting of differentiated human keratinocytes. The keratinocytes differentiate into a stratum corneumlike layer, whereas the dermal-epidermal junction forms a layer similar, but not identical to, the basement membrane. We exposed LSE to 50 cercariae for 0, 3, 6, 20, and 30 hr at 37 C, and the percentage of penetration was evaluated by counting cercariae remaining on the LSE surface. No cercarial penetration was observed in the first 15 min of exposure; however, penetration was detected at all other times. Maximum penetration rates were observed at 20 hr (80%). In other experiments LSE was pretreated topically with 0 or 4 micrograms/cm2 linoleic acid, then exposed to between 800 and 1,000 cercariae for 18-20 hr at 37 C. LSE pretreated with linoleate had significantly higher penetration rates than untreated membranes (81% +/- 2.51% vs. 65.9% +/- 6.97%, P = 0.03). Increasing linoleate concentrations from 10 to 40 micrograms/cm2 gradually decreased the ability of cercariae to penetrate the membrane. Some LSE membranes also were processed for light microscopy, and we present photomicrographs showing schistosomulae within the epidermal and dermal layers of the LSE. We conclude that despite the time it takes for cercariae to penetrate LSE, these membranes may allow investigators to examine, in vitro, host-parasite interactions at the level of the skin. PMID- 8501606 TI - Excystment in vitro of Cotylurus cornutus (Trematoda: Strigeidae) metacercariae. AB - An acid-medium pretreatment appeared to be essential for in vitro excystation of Cotylurus cornutus metacercarial cysts. Both acid-pepsin or acid-saline were effective but optimum excystation occurred after 15 min acid-pepsin pretreatment and subsequent 2 hr treatment at 41.5 C in an alkaline bile salt-trypsin medium. The rate of excystation was rapid, reaching 78.1% by 1 hr and increasing to 84.3% after 2 hr. Storage of metacercarial cysts up to 16 wk at 4 C in sterile Locke's 1:1 solution did not alter cyst viability. PMID- 8501607 TI - Intraspecific diversity in the response of Trypanosoma cruzi to environmental stress. AB - Epimastigotes of 5 Trypanosoma cruzi stocks were cultivated in liver infusion tryptose (LIT) medium at 23-35 C or cocultivated with vertebrate cells at 35 C. A temperature decrease from 26 to 23 C resulted in a stable 60% increase in population doubling time. In zymodeme I and II stocks, a temperature increase to 35 C resulted in a transient approximately 25% increase in doubling time during the first month followed by a approximately 30% decrease after 2 mo. A zymodeme III stock did not grow at 35 C. Flow cytometric analyses showed that the total DNA/cell, guanine + cytosine (G-C), and adenine + thymidine content of 2 zymodeme II stocks increased by 3-11% when cultivated in LIT at 35 C, whereas the DNA values of 2 zymodeme I stocks did not change. The increased DNA levels, due predominantly to an increased kinetoplast G-C content, returned to normal levels when the culture temperature was reduced to 26 C. The effects of cocultivation with vertebrate cells at 35 C were identical to cultivation in LIT at 35 C except that the DNA increase in a zymodeme II stock was not stable. Total DNA/cell, nuclear, and kinetoplast DNA decreased by 8-13% upon prolonged cocultivation. No change in total protein, antigen profiles, complement sensitivity, or heat shock protein gene expression was observed as a consequence of culturing the parasites above 26 C. PMID- 8501609 TI - Trichuris vulpis infection in an Indian tribal population. AB - Stools from 28 of the 82 inhabitants on remote Little Andaman Island in India were examined for parasite eggs and cysts. Trichuris trichiura eggs were found in 27, Trichuris vulpis eggs in 5, Strongyloides stercoralis larvae in 3, hookworm eggs in 15, Entamoeba histolytica and Entamoeba coli cysts each in 9, Giardia lamblia in 6, Retortamonas sp. in 3, Iodoamoeba sp. in 2, and Chilomastix sp. in 2 stools. Ascaris lumbricoides eggs were not seen. The occurrence of T. vulpis eggs in 5 stools and the absence of A. lumbricoides eggs were considered unusual findings. PMID- 8501608 TI - Prevalence of Cryptosporidium sp. and Isospora belli among AIDS patients attending Santos Reference Center for AIDS, Sao Paulo, Brazil. AB - From March 1991 to February 1992, 276 stool samples from 131 patients with the acquired immunodeficiency syndrome (AIDS) (average, 2.1 samples per patient) and stool samples from 81 presumed immunocompetent individuals were studied for the prevalence of Cryptosporidium sp. and Isospora belli. The techniques employed were a modified formol-ether concentration, carbol (phenol) auramine staining, and a modified Kinyoun acid-fast method. The prevalence of both coccidia among AIDS patients was 25.9% (34 of 131). Cryptosporidium sp. oocysts were demonstrated in 25 (19.1%) AIDS patients and I. belli in 13 (9.9%). Coinfection for coccidia of both species was found in 4 (3%) AIDS subjects. Among the presumed immunocompetent individuals, coccidia were not demonstrated in their 81 stool specimens. This study, like others, confirms the worldwide importance of these coccidia among AIDS patients and the necessity of suitable techniques for demonstration of oocysts in stool samples. PMID- 8501610 TI - Establishing jurisdiction through forensic parasitology. PMID- 8501611 TI - Maternal observations of ocular alignment in infants. AB - Seventy-five infants of state-registered orthoptists were observed by their mothers from birth to at least 6 months of age, with particular attention paid to the nature of any deviations noticed in the first few weeks. Most of the infants showed brief periods of inaccurate vergence during the first 2 months, with a wide variation in the amount of deviation seen, despite going on to develop normal binocular single vision. Most deviations were transient, unilateral, alternating esodeviations. There was a statistically significant relationship between the time that deviations were noticed and the development of demonstrable binocular convergence. Few exodeviations were found, contrasting with previous studies, and it is suggested that neonates are more likely to achieve binocular single vision when interacting with their mothers. PMID- 8501612 TI - Cyclic strabismus without binocular function. AB - Various forms of cyclic strabismus have been described. A cyclic variation in binocular function modifying a tendency to strabismus is said to be the underlying mechanism. Cyclic esotropia developed in two adult patients, one having no demonstrable binocular function and the other having suffered complete unilateral visual loss in the affected eye. In each case, on the "good days" there was still a manifest esotropia, in contrast to those patients with cyclic esotropia and good binocular function in which the eyes are straight on the "good days." The presence of binocular function is not required for the development of cyclic strabismus, although the level of binocular function is correlated with the ocular alignment on the "good days." PMID- 8501613 TI - Good visual result following early penetrating keratoplasty for Peters' anomaly. AB - Visual results following penetrating keratoplasty for congenital corneal opacities have been generally disappointing, prompting many ophthalmologists to recommend no surgery for congenital, monocular corneal opacities. A 14-day-old boy had a penetrating keratoplasty performed for unilateral Peters' anomaly and microcornea. Visual acuity 49 months after surgery was 20/40 and peripheral fusion was present. Early surgery with early suture removal, amblyopia therapy, frequent clinical examinations, and motivated, well-informed parents were important factors in obtaining a good visual result. PMID- 8501614 TI - Myoblast transfer therapy in the treatment of ptosis: a preliminary study. AB - Congenital ptosis with poor levator function is now managed by frontalis suspension techniques. While this procedure is better than those used in the past, serious shortcomings exist. A technique producing more normal lid function would be a beneficial addition to surgical management. Since congenital ptosis is thought to be a focal myopathy, we investigated the potential of myoblast transfer therapy in myopathic levator palpebrae superioris. Satellite cells harvested from temporalis muscle were grown as clones, labeled with Dil, and transplanted into experimentally myopathic levator muscle of the same animal. Within 2 weeks, the injected cells were found to be incorporated into muscle fibers within the levator basal lamina. The control side appeared myopathic with very little muscle regeneration. The presence of Dil labeled muscle fibers in the experimental muscles strongly suggests their origin from the injected cells. Electron microscopy of nearby sections showed these fibers to be maturing striated muscle. We feel that the development of this technique may make autogenous myoblast transfer therapy a useful treatment for congenital ptosis and other focal myopathies. PMID- 8501615 TI - A comparison of the success rates of resident and attending strabismus surgery. AB - Residency training involves surgery by resident surgeons at various levels of experience and proficiency, supervised by an experienced attending physician. We reviewed the results of strabismus surgery performed at four institutions with two residency training programs. Five hundred twenty-two cases with follow up greater than 6 weeks were evaluated. These cases included 315 attending procedures and 207 resident procedures under direct attending supervision. Success was defined as a strabismic deviation of 8 prism diopters or less. Average postoperative follow-up was 57 weeks and did not differ between groups. There was no statistical difference between the resident success rate of 58% (121/207) and the attending success rate of 69% (217/315) after adjusting for population differences. The average final deviation of the patients postoperatively was 7 delta for the attending group and 10 delta for the resident group. Amblyopia was significantly more frequent in the resident cases (P < .001). Adjustable sutures were used significantly more often in attending cases (P < .0001). This study supports the premise that resident strabismus surgery is as successful as attending surgery. PMID- 8501617 TI - Results of a single lateral rectus resection for divergence and partial sixth nerve paralysis. AB - A single 5.5-millimeter to 8.0-millimeter lateral rectus resection eliminated diplopia in five of six adult patients with divergence paralysis and in all three patients with a sixth cranial nerve paresis. Preoperative distance esotropia ranged from 11 to 20 prism diopters in primary gaze. Prism therapy failed in seven of nine patients. Lateral incomitance was reduced in three patients with a mild limitation of abduction preoperatively, but was not induced in the six patients with divergence paralysis. Significant overcorrection of the near esodeviation did not occur. A single lateral rectus resection can effectively eliminate diplopia in selected patients with divergence and partial sixth nerve paralysis. PMID- 8501616 TI - Bilateral synergistic divergence. PMID- 8501618 TI - Convergence insufficiency in thyroid eye disease. AB - The incidence of convergence insufficiency in patients with thyroid ophthalmopathy and their response to convergence exercise is unknown. Twenty seven consecutive patients with thyroid eye disease (TED) were evaluated prospectively. Six patients with symptomatic convergence insufficiency obtained varying degrees of subjective and objective benefit from treatment. None of the six had other TED-related complaints that required therapeutic intervention. The study findings should alert the clinician to consider convergence insufficiency in patients with TED and nonspecific ophthalmic symptoms. PMID- 8501620 TI - Implantation in children. AB - With the development of posterior chamber lenses and continuous curvilinear capsulorhexis, and with the availability of viscoelastic agents, the use of intraocular lenses (IOLs) in children is becoming more popular. Since 1982, we have implanted posterior chamber IOLs (PC-IOLs) in the capsular bags of 61 cataractous eyes of 46 children and adolescents. The goal was in-the-bag placement facilitated by the use of a small capsulectomy, and, since 1984, by the use of the continuous curvilinear capsulorhexis. Forty-four cataracts were congenital, 13 were traumatic, and 4 were developmental. Cataract extraction with IOL implantation was performed in 16 (26%) preschool cases (ages 2 through 5), in 31 (51%) child cases (ages 6 through 12), and 14 (23%) adolescent cases (ages 13 through 18). Surgical and postoperative complications were minimal. Visual results were good. Fifty-six percent of preschoolers, 87% of children, and 86% of adolescents achieved 20/40 or better best corrected vision, with 79% of the total cohort achieving 20/40 or better. Overall, 35% achieved an uncorrected visual acuity of 20/40 or better. All but two cases had improvement in best corrected vision; if 20/20 was not attained, the cause was mainly due to deprivation amblyopia. Forty-eight percent of patients were within a diopter of emmetropia. PMID- 8501619 TI - Ophthalmic features of Alagille syndrome (arteriohepatic dysplasia). AB - Eight patients with Alagille syndrome (AGS) are reported. In addition to previously reported findings of posterior embryotoxon, pigmentary retinopathy, and choroidal folds, new findings include decreased axial eye lengths, small corneal diameters, and shallow anterior chambers. Optic disc swelling was noted ophthalmoscopically and abnormally increased orbital subarachnoidal fluid was detected through measurements of the arachnoidal diameters with standardized echography. PMID- 8501621 TI - Laser therapy for retinopathy of prematurity. AB - Nine patients were treated with indirect ophthalmoscope argon laser photocoagulation for threshold retinopathy of prematurity (ROP). A total of 16 eyes were treated at an average postconceptional age of 36.31 weeks. All eyes demonstrated regression of threshold ROP. Follow up was between 1 and 14 months postoperatively. Laser photocoagulation for ROP may be an effective alternative in treating high risk levels of ROP. PMID- 8501622 TI - Ocular findings in premature infants with grade IV intraventricular hemorrhage. AB - Grade IV intraventricular hemorrhage (IVH) is a severe complication of premature birth. We retrospectively performed serial exams on 13 infants with grade IV IVH and compared their ocular findings to 11 infants matched by gestational age and birth weight without an IVH. All children in the study were initially examined in the neonatal unit within 8 weeks after birth. Subsequent periodic eye exams were performed until 3 to 7 years of age. Of the 13 grade IV IVHs, there was a 92% incidence of ocular abnormalities, compared to a 73% incidence in the premature group without IVH. The children with grade IV hemorrhages had a statistically significant increased incidence of severe eye disease with resultant visual loss (38%) compared to the non-IVH group. Loss of vision was due to optic atrophy and retinopathy of prematurity. Grade IV IVH children are at high risk for severe eye disease and should have early and frequent ophthalmologic exams. PMID- 8501623 TI - Medial rectus electromyographic abnormalities in Duane syndrome. AB - We report on four patients from the botulinum toxin clinic at Moorfields Eye Hospital with Duane syndrome, who exhibited paradoxical medial rectus activity. EMGs were performed with a standard toxin needle and were qualitative in nature. Current physiodynamic theories as to the etiology of Duane syndrome are based on an aberrant innervation of the lateral rectus. Paradoxical electromyographic activity of the medial rectus may occur in Duane type I syndrome. A possible explanation for this finding is that the medial rectus may receive aberrant innervation but this may not be physiodynamically significant. We postulate that peripheral innervational anomalies may be secondary to, or coexist with, a brain stem anomaly. If an extraocular muscle possesses a dual innervation, then electromyographic abnormalities, without physiodynamic significance, may occur if the recording electrode comes into contact with muscle fibers innervated by a nerve that supplies a small segment of muscle. PMID- 8501626 TI - The quality of medical care. PMID- 8501624 TI - Ocular manifestations of deformational frontal plagiocephaly. AB - Frontal plagiocephaly can be caused by two mechanisms: craniosynostosis and external deformational pressure. Synostotic plagiocephaly is known to be associated with vertical strabismus and contralateral head tilt. Thirteen patients with deformational frontal plagiocephaly were examined to evaluate head position, ocular motility, and alignment. Nine of the patients (70%) were found to have ipsilateral torticollis, but only one patient had strabismus and this was a horizontal deviation not obviously associated with head position. The clinical features of synostotic and deformational plagiocephaly are discussed to distinguish the two conditions, which have a different treatment and outcome. PMID- 8501625 TI - Etiology of eyelid retraction in children: a retrospective study. AB - Eyelid retraction in an adult occurs usually secondary to Graves' ophthalmopathy, but in children the diagnosis is often obscure. To our knowledge, there are no reports reviewing the relative frequency of the various etiologies of eyelid retraction in children. We reviewed the records of our Pediatric Service from 1976 to 1991 and identified 16 children with eyelid retraction. The eyelid retractions were unilateral in 11 cases and bilateral in five cases, and were the result of five different identifiable causes. Unilateral eyelid retraction was associated with congenital aberrant innervation of the third nerve (3), levator fibrosis (2), hemangioma (1), hyperthyroidism (1), craniosynostosis (1) and Down syndrome (1). Bilateral eyelid retraction was associated with either hyperthyroidism (2) or bilateral optic nerve anomalies with vertical nystagmus (2). Seven of our 11 patients with unilateral retraction had an identifiable etiology, and the remaining four patients had incomplete evaluations. Imaging studies were diagnostic in four of nine patients so studied. Based on our findings, we recommend thyroid studies in all patients with eyelid retraction without aberrant innervation, and neuroimaging if thyroid function is normal. PMID- 8501627 TI - Risk factors for posterior capsular pearling after uncomplicated extracapsular cataract extraction and plano-convex posterior chamber lens implantation. AB - We retrospectively reviewed 542 consecutive cases of extracapsular cataract extraction with implantation of a plano-convex laser ridge posterior chamber intraocular lens. We were interested in the incidence and probability of the development of postcapsular epithelial pearling that required laser capsulotomy and the risk factors associated with it. After four years of follow-up, 21% of all cases had developed pearling. Over the same period, the probability of pearling, as determined by the Kaplan-Meier curves, was 29% with a 95% confidence interval between 22% and 36%. After one year of follow-up, the probability of pearling was 5%; after two years, 15%; after three years, 24%. Younger age (50 years or less), larger optic, and smaller IOL were identified as significant risk factors when each of these factors was analyzed separately. When all risk factors were studied together, and after applying confounding statistics, only younger age was identified as a significant risk factor (P = .003). PMID- 8501628 TI - Incidence of posterior capsule opacification in eyes with exfoliation syndrome and heparin-surface-modified intraocular lenses. AB - Conventional poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) and heparin-surface-modified (HSM) IOLs were implanted after extracapsular cataract extraction in 40 human eyes with exfoliation syndrome. The study was double masked and randomized. Two years after surgery 17 cases with HSM IOLs and 15 with PMMA IOLs were examined. We observed that pigment and cell deposits were more frequent on the PMMA than on the HSM IOLs. The incidence of posterior synechia formation was similar in both groups. However, the incidence of neodymium:YAG laser posterior capsulotomy and posterior capsule opacification was more frequent in the PMMA IOL group. Visual acuity did not differ between the two groups before or two years after surgery. The results suggest that in eyes with exfoliation syndrome, implanting an HSM IOL reduces the incidence of posterior capsule opacification often associated with extracapsular cataract extraction. PMID- 8501629 TI - Experimental evaluation of posterior capsule opacification and intraocular lens decentration: comparison of intraocular lenses of 12.5 mm and 14.0 mm diameter. AB - Most posterior chamber intraocular lenses (IOLs) in common use today measure 13.5 mm to 14.0 mm in diameter. Some investigators recommend using smaller lenses (e.g., 12.0 mm to 12.5 mm). To investigate the effect of smaller lenses, experimental phacoemulsification procedures were performed in 16 eyes of white rabbits using two intraocular lens sizes: 14.0 mm and 12.5 mm. Each lens was evaluated for its effects on posterior capsule opacification and optic decentration, two of the most common complications of modern cataract surgery and intraocular lens implantation. The 12.5 mm lens showed a slightly smaller amount of decentration than the larger lens and a comparable amount of posterior capsule opacification. PMID- 8501630 TI - Long-term results of myopic epikeratoplasty. AB - Twenty-three eyes of 20 patients who had had myopic epikeratoplasty were evaluated and the mean 21-month postoperative results (range: 12 to 47 months) tabulated. Average preoperative myopia was -16.7 diopters (D) spherical equivalent (range: -10 to -33 D), and average postoperative refractive correction was 13 D. Of 22 eyes, 17 eyes (77%) were within 4 D of emmetropia. Preoperative visual acuities without correction were between 2/200 and 20/100 (average = 2/40); postoperative acuities were between 2/200 and 20/20 (average = 20/40). Average preoperative best corrected visual acuity was 20/30. Best corrected visual acuities were unchanged or improved in 82% of cases. Re-epithelialization was complete within an average of seven days (range: three to 16 days) postoperatively except in one case in which the lenticule was removed because re epithelialization did not occur. Five cases showed progressive loss of lenticular power. PMID- 8501631 TI - Optics for photorefractive keratectomy. AB - Matrix calculations are applied to Gaussian optics in the study of myopic correction by photorefractive keratectomy. The Colliac matrix formula determines the postoperative anterior curvature radius of the treated cornea. It also calculates the maximal depth of the removed corneal tissue and the ablation zone diameter needed to achieve emmetropia. PMID- 8501632 TI - Biocompatibility of surface-modified intraocular lenses. AB - We evaluated the biocompatibility of three kinds of intraocular lenses: heparin surface-modified, surface-passivated, and regular poly(methyl methacrylate). Each lens type was implanted in 30 eyes. The cases were followed for one year. Biocompatibility was assessed by the degree of postoperative inflammation and capsule opacification. There was no significant difference between the surface passivated and regular groups on both indices, but there was less postoperative inflammation in the heparin-surface-modified group. The incidence of posterior capsule opacification was greater in the heparin-surface-modified group than in the surface-passivated and regular groups, but the difference was not statistically significant. PMID- 8501634 TI - Reduction of postoperative against-the-rule astigmatism by lateral incision technique. AB - A group of 80 preoperative against-the-rule (AR) eyes had cataract removal and intraocular lens implantation with lateral (temporal) incision and suturing. Fifty-six of the 80 eyes had extracapsular cataract extraction (ECCE) and 24 had phacoemulsification (KPE) with capsulorhexis. For both procedures, subgroups (21 of ECCE, ten of KPE) with high preoperative AR astigmatism (> or = -2.0 D) were evaluated. Analysis of the postoperative data provided the following: (1) induced postoperative cylinder decrease, (2) effect of cutting and not cutting sutures, (3) induced axial shift, (4) postoperative astigmatic change as a function of time, and (5) comparative effectiveness of ECCE and KPE lateral incision procedures in reducing postoperative AR astigmatism. PMID- 8501633 TI - Induced astigmatism and its decay with a frown incision. AB - Forty consecutive patients selected for cataract extraction by phacoemulsification were studied to evaluate prospectively the amount of and changes in surgically induced astigmatism from a 5 mm to 6 mm pocket incision with the external opening made convex against the limbus (frown incision). All incisions had an internal corneal valve and were closed by a single X-stitch to counteract the relaxing effect of the pocket in the 90-degree meridian. Surgically induced astigmatism calculated by simple subtraction was 0.64 +/- 0.90 diopters (D) (P < .0001) on the first postoperative day, 0.03 +/- 0.58 D (P = .75) six weeks after surgery, and -0.18 +/- 0.44 D (P = .01) six months after surgery. Calculated from polar equivalents, the induced astigmatism on the first postoperative day was 0.98 D +/- 1.03 D (P = .0001), after six weeks -0.11 D +/- 0.64 D (P = .30), and after six months -0.28 D +/- 0.49 D (P = .0009). On the first postoperative day 42% of eyes had less than 0.5 D of induced astigmatism, 68% had less than 1.0 D, and 79% had less than 1.5 D. After six weeks the respective percentages increased to 61%, 97%, and 97% and after six months to 84%, 100%, and 100%. The distribution of patients with against-the-rule, oblique, and with-the-rule astigmatism preoperatively was nine, 20, and 11, respectively, and 11, 19, and nine after six months. The amount of astigmatism induced from the 5 mm to 6 mm frown incision did not differ from that found in previously published studies of smaller incisions (to about 4 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501635 TI - Modified corneoscleral incision to reduce postoperative astigmatism after 6 mm diameter intraocular lens implantation. AB - I modified the corneoscleral incision for cataract surgery so the incision is located between the 9 o'clock and 12 o'clock positions and termed it the BENT incision (abbreviated from "between nine and twelve o'clock"). I made the incision on 110 patients for phacoemulsification and 6.0 mm diameter poly(methyl methacrylate) intraocular lens implantation and analyzed postoperative corneal astigmatism. The results revealed that the surgically induced astigmatism was 0.3 diopters of with-the-rule shift in the early postoperative weeks and remained virtually unchanged for the subsequent 24 weeks. This amount of astigmatism was significantly smaller and more stable than that of the conventional superior incision performed on 59 patients. A more rapid stabilization of astigmatism after the BENT approach resulted in better uncorrected visual acuity in the early postoperative period. These findings suggest that corneal astigmatism after cataract surgery is affected by the mechanical force of eyelids and extraocular muscles. The BENT incision would effectively minimize the wound-stretching forces and result in earlier stabilization of a lesser degree of postoperative corneal astigmatism. PMID- 8501636 TI - Vector analysis of astigmatism. Adding and subtracting spherocylinders. PMID- 8501637 TI - Contrast sensitivity and visual acuity in patients with early cataracts. AB - In a population of 188 nondiabetic patients with early cataracts or nuclear brunescence, we assessed the degree to which contrast sensitivity function (CSF) provided more information about a patient's visual disability than high contrast visual acuity measurements. Data collected included LOCS II cataract classification, Bailey-Lovie visual acuity (LogMAR score), Lotmar interferometric visual acuity (LI VA), and distance contrast sensitivity function (CSF) using the Vistech 6500. Generalized least squares regression models in which CS was the dependent variable and either LogMAR score or LI VA was among the independent variables were used to ascertain whether CSF provided additional information about visual disability to that provided by LogMAR score or LI VA. Contrast sensitivity function was decreased only by nuclear opalescence at high frequencies (12 to 18 cpd); for all other cataract types and nuclear color, CSF testing provided no more information about cataract-related visual loss than LI VA or LogMAR score. Measurement of CSF using the Vistech 6500 system in patients with early cataracts provides information on visual dysfunction beyond that provided by LogMAR score or LI VA only in patients with nuclear opalescence, and that may not be clinically significant. PMID- 8501638 TI - Long-term results of intraocular lens implantation in pediatric patients. AB - Between 1980 and 1990, 42 eyes of 34 patients (age range: 18 months to 18 years) were implanted with an intraocular lens, with 29 being primary implantations and 13 secondary. The primary implantation group comprised patients with congenital, developmental, and traumatic cataracts. Patients in the developmental and traumatic cataract groups achieved the best visual acuity. Those with congenital cataracts had the poorest visual outcome. Follow-up ranged from a minimum of three months to more than ten years. Overall the patients demonstrated an improvement in visual acuity and the psychological advantage of enhanced visual function without spectacles or contact lenses. We conclude that with proper case selection and a controlled, skilled surgical approach, the use of an intraocular lens for visual rehabilitation in the pediatric age group is a feasible approach. PMID- 8501640 TI - Endocapsular hyphema. AB - A 67-year-old female developed an endocapsular hyphema after uncomplicated extracapsular cataract surgery. With a neodymium:YAG laser capsulotomy, we drained the blood into the vitreous and restored excellent visual acuity. We hypothesize that endocapsular hyphemas may fail to resorb because of sequestration of the clot from the fibrinolytic system of the anterior chamber. PMID- 8501639 TI - Healon GV in extracapsular cataract extraction with intraocular lens implantation. AB - A randomized masked study was performed to compare Healon GV, a new higher molecular weight sodium hyaluronate viscoelastic, with Healon in extracapsular cataract surgery with posterior chamber intraocular lens insertion. Seventy patients were randomly divided into two groups. Postoperative intraocular pressures, pachymetry, endothelial cell counts and morphology, amount of viscoelastic and irrigating solution used, difficulty of surgery, and postoperative flare and cells were measured. Postoperative pressures were not significantly different between the Healon and Healon GV treatment groups, except at the eight-hour observation period, when the pressure was higher in the Healon GV group (P = .02). There was a significant (P = .002) reduction in the amount of viscoelastic required in the Healon GV group. Cell counts and morphology were not significantly different between the groups. Other parameters showed no significant difference. Clinically, Healon GV handled like Healon during instillation into the anterior chamber and aspiration at the end of the case. It did, however, appear to be much more effective at maintaining the anterior chamber, as demonstrated in the smaller amount of viscoelastic required. PMID- 8501641 TI - Radial keratotomy in an elderly patient. AB - A 74-year-old male complained of poor vision and diplopia as a result of cataract extraction and intraocular lens implantation. On refraction, we found -6.25 diopters (D) of myopia in his right eye. The patient, dissatisfied with wearing contact lenses and spectacles to correct vision, opted to have refractive corneal surgery. We performed a four-incision radial keratotomy with a 4 mm clear zone. This resulted in a 3.75 D (-2.5 D residual myopia) reduction in myopia at two months of follow-up. Our results indicate that radial keratotomy may be useful for correcting unacceptable myopia in older patients. PMID- 8501643 TI - Split and lift: nuclear quadrant management for phacoemulsification. AB - A bimanual technique for handling the nuclear quadrants created during "in situ fracture" or "divide-and-conquer" phacoemulsification after capsulorhexis is described. This technique involves lifting the sharp apex of each nuclear quadrant anteriorly, permitting centralization of the quadrant for emulsification. Complications and difficulties associated with other methods of nuclear quadrant handling, such as tumbling and use of high vacuum level settings, are avoided. PMID- 8501644 TI - Exchange of IOGEL hydrogel one-piece foldable intraocular lens for bag-fixated J loop poly(methyl methacrylate) intraocular lens. AB - In 1990, IOGEL lenses placed in the capsular bag were reported to displace into the vitreous after neodymium:YAG (Nd:YAG) laser capsulotomy. We exchanged a bag placed IOGEL lens in one patient after erroneous biometry and capsular opacification. The technique and results of lens explantation, aspiration of Elschnig pearls, and in-the-bag implantation of a modified J-loop poly(methyl methacrylate) (PMMA) lens are demonstrated. Removal of the soft and nonadhesive IOGEL lens was easy. The capsule pockets held patent by the flanges of the taco style IOGEL lens allowed for easy insertion and bag fixation of the J-style loops. Visual acuity improved from 20/60 to 20/20. Centration of the exchange IOL was satisfactory. In a series of 61 Nd:YAG laser posterior capsulotomies, we did not observe the reported tendency of IOGEL lenses to luxate posteriorly. Therefore, we recommend Nd:YAG discission of the posterior capsule as the preferred approach to posterior capsule opacification with IOGEL lenses. However, the technical ease of the technique makes the explantation and replacement of IOGEL lenses by a bag-fixated PMMA IOL a valid option to correct an erroneous biometry. PMID- 8501642 TI - Defects in an injection-molded intraocular lens. AB - Injection-molded intraocular lenses may undergo structural changes when exposed to solvents and fixatives during post-mortem examination. We report a case in which this phenomenon was seen in an injection-molded lens. We were able to duplicate these changes by immersing injection-molded lenses in 60% alcohol for 48 hours. PMID- 8501645 TI - Comparing the cell population on different intraocular lens materials in one eye. AB - We developed a method to evaluate cell adherence to different intraocular lens (IOL) materials in one eye in which we coated one half of the anterior surface of a poly(methyl methacrylate) (PMMA) IOL with poly(dimethyl siloxane), a silicone material. The lenses were implanted in the anterior chamber of rabbit eyes without lens extraction. Postoperative cellular reaction on the IOL surfaces was studied by specular microscopy. The IOLs were fixed in situ, removed from the eyes, and stained with hematoxylin-eosin so we could evaluate the cell population on the silicone and PMMA surface. Fewer cells were scattered on the silicone surface than on the PMMA surface. This method excludes surgical effects and allows a comparison of various IOL materials in the same eye. PMID- 8501646 TI - The gliding nucleus. AB - The lens glide is a disposable sterile plastic piece designed to achieve smooth, easy, safe expression of the nucleus in planned extracapsular cataract extraction. The advantages of the technique include prevention of iris prolapse or iris trauma, controlled nucleus extraction without sudden nucleus expulsion, direction of the nucleus toward the external opening, and prevention of malengagement of the nucleus to the anterior chamber angle or vitreous cavity. Using the glide facilitates extraction of a nucleus through a small limbal or scleral incision. Combining the glide with other modern surgical techniques, such as scleral tunnel small incision, capsulorhexis, and hydrodissection, results in a no-stitch low astigmatic wound and stable intraocular lens fixation in the capsular bag. PMID- 8501647 TI - Consultation section. Phacoemulsification with implantation of an Azar anterior chamber intraocular lens (IOL). PMID- 8501648 TI - Postoperative lens deposits. PMID- 8501649 TI - Occurrence of erroneous anterior chamber depth in the SRK/T formula. PMID- 8501650 TI - Antibacterial concentrations. PMID- 8501651 TI - High hyperopia after radial keratotomy. PMID- 8501652 TI - Effect of contact between lens and capsule. PMID- 8501654 TI - Notes from the American Society of Anesthesiologists annual meeting. PMID- 8501653 TI - The antiplatelet effects of aspirin and related component drugs on the surgical patient. AB - Any medication has potential to cause adverse side effects. Some medications prescribed for a specific function are also widely available as over-the-counter products to treat menstrual discomfort, colds and allergies, or they may act as sedatives. For example, aspirin (ASA), medications that contain ASA, and nonsteroidal anti-inflammatory drugs all have antiplatelet properties. The surgical patient who regularly uses these medications may potentially develop postoperative hemorrhage. PMID- 8501656 TI - Toward a new order: boundary management. AB - According to recent research data, interactions between people will be impacted by four types of psychological boundaries. Each of the boundaries has specific key distinctions that identify them. If the boundary can be identified, then specific skills can be used to facilitate successful, positive interactions between people. These data provide a strong foundation on which managers can build as they develop new skills to cope with new demands. PMID- 8501655 TI - Establishing the reliability and validity of a new instrument: pilot testing. AB - Development of instruments to measure psychosocial variables is a complex process that begins with concept analysis and concludes with pilot testing to establish initial reliability and validity properties. Although the instrument development process is lengthy. PACU nurses are encouraged to follow all steps; if they do not, they will be unsure of what is measured or the meaning of the finding. Discussed here is the final phase of the instrument development process; calculating and analyzing construct validity and internal consistency reliability. An example is given that applies reliability and validity methods to a hypothetical instrument. PMID- 8501657 TI - Caring about the elderly: opportunities and obligations. AB - The number of people age 60 and older worldwide is expected to increase to 612 million by the year 2000. As a whole these individuals are much healthier and lead more active, independent lives than their ancestors. Health care for this growing population presents many challenges, opportunities, and obligations. Nurses who care about the elderly may be lacking the current information and specific educational preparation needed to care for them. The author discusses some important aspects of home care for elderly patients in the ambulatory surgery unit. PMID- 8501659 TI - Of goldmines and gamblers: reclaiming a pioneer spirit. PMID- 8501658 TI - Mission: Philippines 1992. AB - A volunteer mission to the Philippine island of Negros for Operation Smile International in February 1992 is retold. Two Virginia PACU nurses share experiences of the situations and circumstances on their first mission, which profoundly affected their personal and professional outlooks and nursing philosophies. PMID- 8501660 TI - Stamp out whining now! PMID- 8501661 TI - The laryngeal mask airway: tool for airway management. AB - The laryngeal mask airway (LMA) is possibly the most significant recent advance in airway management. Designed to be passed into the hypopharynx without a laryngoscope, the LMA was conceived after bioengineering principles were applied to postmortem specimens of the adult larynx. The LMA has gained widespread, worldwide popularity and was approved for use in the United States in 1992. Sound knowledge of this device is important for all health care workers involved in airway management because it may become a standard item of resuscitation equipment when intubation is difficult. Nurses in the PACU may also be involved in management of anesthetized patients who still have an LMA in place. This article acquaints the reader with the LMA; reviews its design, uses, and limitations; and details some of the controversies related to its use in the PACU. Policies about the LMA need to be defined by PACU nurses and anesthesiologists according to the best information available and the particular requirements of the individual PACU. PMID- 8501662 TI - Management of minor adverse effects encountered during narcotic administration. AB - Presented are four clinical scenarios of patients receiving narcotics to control pain of various etiologies. In all cases minor adverse effects necessitated intervention so that continued use of these agents was possible. The four cases illustrate common adverse effects, including nausea, vomiting, pruritus, and dysphoria, that may occur during narcotic administration. Management strategies to deal with these and other common non-life-threatening effects of narcotic agents are presented. PMID- 8501663 TI - Black looks ... at audit. PMID- 8501664 TI - A look at the statistical overview (or meta-analysis) AB - In essence, the statistical overview (or meta-analysis) does little more than many medical scientists and practising clinicians have been attempting for years: estimating the average size of an effect from an apparently disparate medical literature. The statistical overview provides a method of pooling the results of comparable trials (or observational studies) which, on their own, may be too small to demonstrate a 'statistically significant' effect. The role for the overview is obvious, the method is relatively simple, but the findings have to be interpreted cautiously, since joining the hypothesis post hoc contravenes one of the essential principles of scientific enquiry. The use of the statistical overview and some of its pros and cons are illustrated in four clinical examples. PMID- 8501665 TI - Physicians' attitudes to the autopsy. AB - The overall autopsy rate (excluding coroner's autopsies) at a large teaching district general hospital over a four year period was 16.5%, but individual rates for ten general physicians varied from 5% to 35%. During this period, the mean autopsy rate for general medicine (14%) was significantly lower than rates for cardiology (21%), geriatrics (23%) and paediatrics (36%), but similar to general surgery (13%). Autopsies were widely perceived as being of benefit to education and research, but physicians were often unaware of their value for confirming the diagnosis and for clinical audit, and over-estimated their actual autopsy rates on average by 50%. High rates (18-30%) were associated with consultants who had a definite policy regarding autopsies and had made this clear to their junior staff. Low rates (6-10%) obtained where there was no consultant policy on autopsies, and were frequently attributed by the consultant physicians to failure by their junior staff. Physicians should be more aware of the value of autopsies, and should take responsibility for increasing and monitoring autopsy requests to improve clinical audit, quality assurance and medical education. PMID- 8501666 TI - The economic implications of therapeutic conservatism. AB - We review the pattern of prescribing medicines in the United Kingdom (UK) and compare it with that in other European markets. The prescribing of medicines in Britain has always been more conservative than in other major European markets such as France, Italy, Germany, and Spain, but the difference is becoming more marked. The conservative nature of the British prescription medicine market is indicated by three international comparisons. First, British doctors prescribe fewer items per patient per year than their counterparts in other European countries. Second, they are less likely to prescribe a product containing a new active chemical entity (NCE) than their counterparts in other countries. This resistance to the use of newer medicines has increased over the past decade. Third, British doctors rely on a progressively smaller number of active substances for a greater proportion of their prescriptions. As a result of these trends the pharmaceutical industry--at least as far as its British sales are concerned--is becoming more dependent on the sales of older products and on the occasional 'blockbuster' to finance its research. Declining uptake of new medicines, coupled with increasing pressure on doctors to prescribe cheaper generics instead of branded medicines, reduces the ability of pharmaceutical companies to fund their investment in research into as yet unconquered diseases. This trend could work against the interests of both patients and the British economy. PMID- 8501668 TI - Medical audit: a second report. A comment on the report. PMID- 8501667 TI - Professional attitudes to cardiopulmonary resuscitation in departments of geriatric and general medicine. AB - Cardiopulmonary resuscitation for the elderly has long been a contentious issue. We have established by means of a postal survey the attitudes of 300 consultant geriatricians, 300 consultant physicians and 249 registered nurses to cardiopulmonary resuscitation. We also audited 400 case notes to document current practice in departments of general medicine and medicine for the elderly. No formal resuscitation policies were in operation. Geriatricians were more likely than physicians to make a positive resuscitation decision (p < 0.001), and involve nursing staff in the decision-making (p < 0.001). All professional groups felt age was unimportant in deciding on resuscitation, while the patients' prognoses and their wishes were most important. Case note audit revealed that geriatricians were better at documenting resuscitation decisions. Inappropriate resuscitation of patients is unacceptable. Each department or hospital ought to have agreed guidelines for cardiopulmonary resuscitation. PMID- 8501669 TI - The end of life in medical practice. A review of a report by The Netherlands Central Bureau of Statistics, 1992. PMID- 8501670 TI - 'Do not resuscitate' orders: the need for a policy. AB - The use of 'do not resuscitate' (DNR) orders is widespread in UK hospitals, but until recently there has been no formal policy for this practice. The decision not to resuscitate should be made on ethical and medical grounds. The ethical implications for such decisions are explored. A review of current practice reveals considerable variation in the way in which DNR orders are made. Patients are rarely involved in the decision. There have been failures of communication between doctors and nurses, and between consultants and their juniors. These issues have now come to public and professional attention. There is a need for coherent national and local resuscitation policies that should take into account the medical, ethical and practical aspects of DNR decision making. PMID- 8501673 TI - The MB PhD programme. Training to be a clinician-scientist in the UK. AB - Rapid changes in the universities and in the organisation of the National Health Service are altering the perception of opportunity for clinical scientists in training. Cambridge University has established an integrated programme that combines training in scientific research and clinical medicine leading to the MB, BChir, and PhD degrees. The need for this and other options in the development of careers for aspiring medical researchers is reviewed here. PMID- 8501671 TI - The 'do not resuscitate' decision: guidelines for policy in the adult. AB - The Royal College of Physicians of London, along with a number of organisations, has considered the policy for 'do not resuscitate' (DNR) orders in relation to cardiopulmonary resuscitation (CPR). On the basis of current attitudes towards the more active involvement of patients in such decisions--advance directives (living wills)--and the usual approach in the UK of seeking the views of relatives or next of kin, general guidelines have been drawn up which take into account the results obtained with CPR. The guidelines encompass only the broad principles, as it is envisaged that each hospital or unit will require a more detailed policy according to local circumstances and facilities. Children have not been included because of the special considerations that relate to neonatal resuscitation and the consents required. PMID- 8501672 TI - Better research ethics committees: comments on guidance from the Department of Health and the European Community. PMID- 8501674 TI - Training in neonatal resuscitation: the views of junior paediatricians. AB - Senior house officers and registrars in one region were asked whether they received any training in neonatal resuscitation in this region and what they thought of it. Training in neonatal resuscitation is variable and often falls short of the guidelines of the Royal College of Physicians of London. The majority of the respondents were dissatisfied with the extent and the level of supervision of their training. The structure and content of training in this subject needs to be reviewed. PMID- 8501675 TI - Postgraduate medical education--comparisons between the United Kingdom and Australia. AB - The strength of postgraduate medical education in the United Kingdom lies in the recognition that it is a continuing process from the preregistration year through the training grades into the stage of independent practice. The continuity derives from the support given to postgraduate deans by the universities, regional health authorities and professional colleges whose various contributions and training activities can be coordinated under the umbrella of the dean's office. This contrasts with the Australian scene where the responsibility for medical postgraduate education is still largely divided between the Australian Medical Council, individual state medical boards and the various professional colleges and faculties. Australia, has, however, devised a shorter basic and higher specialist training structure that ensures an earlier and more productive entry to independent practice. Australia has also accepted the principle of recertification which would seem to be a logical sequel to the committed system of defining and maintaining high standards of delivery of health care in the United Kingdom. PMID- 8501676 TI - Common trunk medicine in the EC. PMID- 8501679 TI - Randomised controlled trials: the Cochrane collaboration. PMID- 8501678 TI - Microbes, molecules and man. The Mitchell Lecture 1992. AB - Robert Koch, the discoverer of the tubercle bacillus, has had a seminal influence on the extraordinary progress in the field of infectious diseases in the past 100 years. Koch's postulates defined the germ theory of disease causation. They have now been confirmed and brought up to date by the application of molecular techniques. Developments in molecular genetics have helped in the elucidation of the pathogenesis of meningitis caused by H influenzae and the role of type b capsule as a determinant of bacterial virulence--and satisfied the requirements of Koch's molecular postulates. This new knowledge has contributed to the development of a successful immunoprophylactic strategy for eliminating Hib disease. Studies in Oxford over the past eight years have confirmed the effectiveness and safety of a routine immunisation programme for the UK. PMID- 8501677 TI - Clinical and public health ethics: conflicting or complementary? The Milroy Lecture 1993. PMID- 8501680 TI - Health care and the American College of Physicians. PMID- 8501681 TI - An elective period visit to Pakistan. PMID- 8501682 TI - Osler's two centenary celebrations. PMID- 8501683 TI - Friends and influence: the history of the '42 Club'. PMID- 8501684 TI - Fraud and malpractice in clinical research. PMID- 8501685 TI - Therapeutic conservatism. PMID- 8501686 TI - Therapeutic conservatism. PMID- 8501687 TI - Risks of sedation in endoscopy. PMID- 8501688 TI - Risks of sedation in endoscopy. PMID- 8501690 TI - So, what is a clinical oncologist? PMID- 8501689 TI - Treating hyperthyroidism with radioactive iodine. PMID- 8501691 TI - Collecting, communicating and using information. PMID- 8501693 TI - Generic substitution. PMID- 8501692 TI - Delays to thrombolysis in the treatment of myocardial infarction. PMID- 8501694 TI - Resuscitation status of the elderly. PMID- 8501695 TI - Clinical vignette. A 7-year-old Bernese Mountain dog with anemia. PMID- 8501696 TI - Deafness assessment services by means of the brainstem auditory-evoked response. PMID- 8501697 TI - A retrospective study of the use of total parenteral nutrition in dogs and cats. AB - The records of all dogs and cats receiving total parenteral nutrition (TPN) over a 43-month period were examined retrospectively. Dextrose, amino acids, lipids, electrolytes, and vitamins were administered by central venous catheter according to published nutrient recommendations; 72 dogs and 12 cats were studied, accounting for 380 patient days of TPN. Duration of TPN administration was 1-14 days with a mean of 4.5 days. Most animals required TPN because of gastrointestinal dysfunction, and more than half of them gained weight during TPN administration. Mechanical complications were frequent. Metabolic complications, especially lipid and glucose intolerance, were also commonly seen. Septic complications were the least frequently encountered, but resulted in patient morbidity and may have contributed to mortality. Most animals receiving TPN were returned to enteral nutrition and discharged. For critically ill animals unable to tolerate enteral alimentation, TPN can be supportive therapy in the treatment of the primary disease. PMID- 8501698 TI - Nephrogenic diabetes insipidus in sibling colts. AB - Nephrogenic diabetes insipidus was diagnosed in two full sibling Thoroughbred colts. Each colt had a history of excessive urination. Extreme polydipsia (greater than 80 L per day) was documented in both colts. Inability to concentrate urine in response to water deprivation, infusion of hypertonic saline, or exogenous vasopressin administration indicated insensitivity of the collecting duct epithelial cells to vasopressin. A diagnosis of nephrogenic diabetes insipidus was further supported by a normal increase in plasma vasopressin concentration after water deprivation in the one colt in which such testing was pursued. PMID- 8501699 TI - Pathophysiology and pharmacologic modulation of hepatic fibrosis. AB - Most chronic liver disorders are accompanied morphologically by the deposition of fibrous tissue within the hepatic parenchyma. This fibrotic tissue compromises hepatic function and contributes significantly to hepatic failure. Fibrosis is a dynamic process associated with the continual deposition and resorption of connective tissue. Therapeutic strategies are emerging whereby this dynamic process can be modulated. Since collagen is the major component of the extracellular matrix deposited in hepatic fibrosis, most anti-fibrotic therapies have been directed toward the control of collagen metabolism. After collagen genes are transcribed and translated into precursor procollagen proteins, a number of post-translational modifications that ensure the deposition of structurally sound collagen within the extracellular matrix occur. A number of drugs can specifically modulate collagen biosynthesis at the transcriptional level or at various post-translational stages. These anti-fibrotic drugs include corticosteroids, azathioprine, penicillamine, colchicine, zinc, prostaglandins, cyclosporine, and interferons. The pharmacologic action of these drugs and the clinical role in veterinary and human fibrotic hepatopathies will be discussed. PMID- 8501701 TI - Embryo cloning in cattle: the use of in vitro matured oocytes. AB - In vitro matured (IVM) bovine oocytes were examined to determine their potential viability in embryo cloning. Activation competence, as monitored by pronuclear formation, increased with oocyte age. Oocytes readily formed a pronucleus when challenged with an electrical pulse 30 h after the onset of maturation. Developmental competence of IVM oocytes tended to increase with oocyte age (P = 0.079). Selection of IVM oocytes on the basis of the presence of a polar body 24 h after the onset of maturation and the size of the follicle from which the oocyte was derived improved development of nuclear transfer embryos (polar body positive 25% versus polar body negative 10%, P < 0.05; large follicle oocytes 31% versus small follicle oocytes 14%, P < 0.05). When selected, IVM oocytes were compared with in vivo matured oocytes recovered from superovulated cows and heifers; no difference was detected for the frequency of embryos produced, pregnancies confirmed between days 50 and 60 of gestation, or the number of calves born. We conclude that selected IVM oocytes are equivalent to in vivo matured oocytes when used for bovine embryo cloning. PMID- 8501700 TI - Cerebrospinal fluid composition of cattle with endotoxin-induced mastitis treated with isotonic (0.9%) or hypertonic (7.5%) sodium chloride. AB - This study examined the safety of intravenous hypertonic saline in cattle with experimental gram-negative endotoxemia. Cerebrospinal fluid (CSF) composition was examined in five control cows and eight treated cows 24 hours after the intramammary infusion of 1 mg of endotoxin. Four of the endotoxin challenged cows were treated intravenously with isotonic (0.9%) sodium chloride and four cows were treated intravenously with hypertonic (7.5%) sodium chloride. Decreased CSF osmolality, and sodium and alpha globulin concentrations and increased CSF concentrations of beta globulin were observed in both endotoxin-challenged saline treated groups. No CSF compositional differences were observed between endotoxin challenged cows receiving isotonic or hypertonic saline. Although no cytologic or biochemical evidence of salt poisoning was observed in cows receiving hypertonic saline, significant changes were observed in the CSF composition of both endotoxin-infused saline-treated groups. PMID- 8501702 TI - Requirement of inner cell mass for efficient chorionic gonadotrophin secretion by blastocysts of common marmosets (Callithrix jacchus). AB - The role of the inner cell mass in the induction of chorionic gonadotrophin synthesis and secretion by the trophoblast of the peri-implantation primate blastocyst was studied in common marmoset monkeys. An in vitro system for the culture of blastocysts commencing with blastocysts collected 8 days after conception was developed. Chorionic gonadotrophin measured in the spent culture fluid was first detected in most blastocysts after 3 or 4 days (day 11 or 12) of culture at a time equivalent to implantation in vitro. Initial secretion of chorionic gonadotrophin coincided with development of parietal endoderm and histological appearance of syncytiotrophoblast in the polar trophoblast. Little chorionic gonadotrophin was secreted by blastocysts with a poorly developed, or absent, inner cell mass. Mural trophoblast removed from blastocysts after 2 days of culture (day 10) grew in vitro as a unilaminar vesicle but failed to secrete significant amounts of chorionic gonadotrophin. However, mural trophoblast from older blastocysts (days 13 and 14) after chorionic gonadotrophin secretion had commenced continued to secrete chorionic gonadotrophin, with trophoblast from day 14 blastocysts secreting significantly more than that from day 13. It was concluded from these studies that while mural trophoblast from marmoset blastocysts will proliferate in vitro in the absence of an inner cell mass, efficient induction of chorionic gonadotrophin secretion requires the presence of the inner cell mass or its derivatives. Once chorionic gonadotrophin secretion has commenced, secretion will continue in the absence of the inner cell mass. PMID- 8501703 TI - Evaluation of ram semen motility by a swim-up technique. AB - The turbidity formed as ram spermatozoa swam up into a clear medium was measured using a colorimeter and this was used as an objective index of sperm motility. Wavelengths of 470-475 nm yielded higher optical densities (OD) than did 520-640 nm. The recommended distance between the light beam and semen-medium interface, and operation temperature were 5 mm and 30-37 degrees C, respectively. Of seven media tested, Tris-glucose was preferred on the basis of results, availability and cost. Diluting semen before testing reduced OD, whereas increasing semen concentration (0.6 to 2.4 x 10(9) spermatozoa ml-1) and the total number of spermatozoa used increased OD. OD gradually increased with time in all experiments (P < 0.001). High positive correlations between OD and known percentages of motile spermatozoa (0.82-0.91 at from 5 to 20 min, all P < 0.001) suggest that this swim-up technique, which is objective and inexpensive, is valid for measurement of sperm motility in rams. PMID- 8501704 TI - Changes in activities of superoxide dismutase and lipid peroxide in corpus luteum during pregnancy in rats. AB - Activities of superoxide dismutase (SOD) and lipid peroxide (LPO) were studied in corpora lutea of pregnant rats. SOD activities, both Mn-SOD and Cu,Zn-SOD, gradually increased in the corpora lutea until day 15 of pregnancy and decreased thereafter until day 21 of pregnancy, in a similar manner to serum progesterone concentration. LPO activities remained low until day 15 of pregnancy, but increased rapidly after day 15 to day 21 of pregnancy. Incubation of the dispersed luteal cells from day 15 of pregnancy in vitro showed that FeSO4 and ascorbic acid, which induce lipid peroxidation, significantly inhibited progesterone secretion. The inhibitory effects of FeSO4 and ascorbic acid were blocked by the simultaneous addition of alpha-tocopherol. These results suggest important roles for SOD and LPO in regulating luteal function during pregnancy. PMID- 8501705 TI - Prediction of fertility by mating latency and photoperiod in nulliparous and primiparous meadow voles (Microtus pennsylvanicus). AB - Mating behavior and litter production of female meadow voles (Microtus pennsylvanicus) housed in long (14 h light: 10 h dark; long day; LD) or short (10 h light: 14 h dark; short day; SD) photoperiods were monitored to determine whether the reduced birthrate of SD females resulted from a lack of copulation. All females mated, but fewer SD females gave birth. LD and SD females fell into three distinct groups based on mating latency. The rapid onset group (RO) mated between 7 min and 9 h after pairing, the intermediate onset group (IO) mated between 16-44 h and the late onset group (LO) mated after 58-262 h of male contact. Sixty-seven per cent of LD females were assigned to group RO, 27% to IO, and 6% to LO. In contrast, 30% of SD females were assigned to group RO, 35% to IO and 35% to LO. Fertility was predicted by mating latency. Sixty-nine per cent of RO, 93% of IO and 33% of LO animals gave birth. In a further experiment, a small mouthed cup was added to the environment to serve as an escape for females wishing to avoid mating. Although females did not use the cup to escape male approaches, mating occurred in only 66% of SD females, but was observed in all LD females. In a final experiment, mating latency and litter production were recorded in primiparous LD and SD females initially observed in the first experiment. Group LO was eliminated in parous females; all primiparous LD and SD females mated within 48 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501706 TI - Ovarian angiogenesis in rabbits: endotheliotrophic chemoattractant activity from isolated follicles and dispersed granulosa cells. AB - To test the hypothesis that angiogenesis is an important variable in ovarian folliculogenesis, we measured endothelial cell migration (chemotaxis) in media conditioned by rabbit ovarian cells. Endothelial cell migration, a reliable predictor of angiogenesis in vivo, was stimulated by media conditioned by isolated intact follicles (0.4-2.2 mm in diameter) from either unstimulated or hCG-stimulated (pseudopregnant) rabbits. In separate experiments, endothelial cell migration was also stimulated by granulosa cell-conditioned media. Follicular chemoattractant activity was associated with a molecular weight greater than 30,000 but was not correlated with follicular size or steroid concentrations in the media, although there was no evidence to suggest that the biological activity detected in media conditioned by either intact follicles or dispersed granulosa cells was the same. Demonstration of nonsteroidal chemoattractant activity in media conditioned by intact follicles or by dispersed granulosa cells provides evidence that follicles secrete a vascular chemotactic factor, and is consistent with a role for angiogenesis in follicle growth. PMID- 8501707 TI - Control of photoperiodic inhibition of luteinizing hormone secretion by dopaminergic and serotonergic systems in ovariectomized Ile-de-France ewes supplemented with oestradiol. AB - The role of dopaminergic and serotonergic systems on LH secretion was investigated in Ile-de-France ewes under different artificial inhibitory photoperiodic regimens. All animals were ovariectomized at the end of the breeding season, chronically treated with an oestradiol implant, and subjected to various changes in daylength for 9 months to inhibit or stimulate their LH secretion. Plasma LH concentration was assessed by taking blood samples twice a week throughout the experiment. The effects of acute intravenous injections of the dopaminergic2 receptor antagonist pimozide (0.08 mg kg-1) and the 5 hydroxytryptamine2 (5HT2) receptor antagonist cyproheptadine (3 mg kg-1) on LH pulsatility were assessed during challenges in four different situations: (1) long days (LD); (2) before short-day response (SD); (3) during refractoriness to short days (RSD); and (4) during inhibition by long days (ILD). LH in blood samples collected twice a week remained low during long days (0.59 +/- 0.03; mean +/- SEM), increased 45 +/- 1.5 days after the onset of short days and decreased 132 +/- 4.9 days later when ewes became refractory to short days, whereas ewes subjected to long days after 91 short days stopped their neuroendocrine activity 19 days earlier (113 +/- 4.7) (P < 0.01). In comparison with the pre-injection period, pimozide significantly increased the mean number of pulses in SD and RSD ewes, but not in LD and ILD ewes: SD: 0 versus 0.45 pulses in 4 h (P < 0.02); RSD: 0 versus 0.9 (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501708 TI - Mechanisms and physiological implications of leucocyte chemoattraction into periovulatory ovine follicles. AB - Leucotactic polypeptide was isolated from follicular-conditioned incubation media by ultrafiltration and reverse-phase high performance liquid chromatography. The bioactive fraction was subjected to amino acid analysis and shown to be abundant in glycine, proline and hydroxyproline. These amino acid residues are common to repetitive sequences of alpha collagens. Synthetic collagen-like peptides composed of repeating triplets of glycine, proline and hydroxyproline (GPH x 3, GPH x 9) were active in attracting white blood cells as measured in vitro using a linear under-agarose assay. Accumulation of leucocytes within extravascular spaces of the theca interna was induced by intrafollicular injection of GPH x 3 or bacterial collagenase. Intrafollicular administration of affinity-purified GPH x 3 antibodies during the immediate preovulatory period inhibited thecal extravasation of leucocytes, but did not negate follicular rupture. However, serum concentrations of progesterone were depressed in antibody-treated animals throughout the ensuing luteal phase. This luteal defect was counteracted by injecting leucocytes into the preovulatory follicle. It is concluded that periovulatory follicles of the sheep secrete collagen-like leucotactic peptides. Once drawn into the follicle, resident inflammatory cells are apparently involved in transforming it into a fully functional corpus luteum. PMID- 8501709 TI - Effects of a single brief period of moderate heating of the testes on seminiferous tubules in hypophysectomized rams treated with pituitary extract. AB - An experiment was conducted to examine the appearance of the seminiferous tubule 20 days after a single exposure of the testes of rams to a scrotal temperature of about 42 degrees C for 45 min. Ten of the animals were surgically hypophysectomized and five were simultaneously heated; these rams were treated twice a day with ovine pituitary extract to avoid modifications in the negative feedback from the testes to the pituitary and consequent changes in gonadotrophin secretion. Six intact rams (three heated and three unheated) were also studied. The pituitary extract significantly increased the testis weight and spermatogonial multiplications from A1 spermatogonia onwards. Twenty days after the heat treatment, testis weight was significantly reduced by heating; both tubular and intertubular tissues were affected. The total length of seminiferous tubules per testis was not modified, whereas the mean seminiferous tubule diameter was significantly reduced after heating. The total number of Sertoli cells per testis was not significantly modified, while their mean cross-sectional nuclear area was significantly reduced by heat treatment. A decrease in the number of all germ cells except A0 spermatogonia, from A1 spermatogonia onwards, was observed. The number of round spermatids decreased by 95 and 90%, slightly more than the diplotene primary spermatocytes (76 and 77%) and elongated spermatids (79 and 85%) in hypophysectomized pituitary extract-treated and intact rams, respectively. Round and elongated spermatids would be derived from germ cells that were respectively leptotene and young pachytene primary spermatocytes at the time of heating, whereas diplotene primary spermatocytes would have been type B spermatogonia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501710 TI - Effect of naloxone and pulsatile luteinizing-hormone-releasing hormone infusions on oestradiol-induced luteinizing hormone surges in immature gilts. AB - The aim of the study was to understand why immature 60-day-old gilts produce delayed low amplitude luteinizing hormone (LH) surges in response to oestradiol benzoate. In Expt 1, gilts (n = 36) were challenged with oestradiol benzoate and subsequently received either no further treatment or were infused with saline or various doses of the opioid antagonist, naloxone, for 6-48 h during the expected LH surge (48-96 h after oestradiol benzoate). No differences were observed among groups in the magnitude or duration of the LH surge. In contrast to the other groups, LH concentrations in gilts infused for 48 h with naloxone did not decrease after the surge period. In Expt 2, gilts (n = 34) were challenged with oestradiol benzoate or sesame oil and subsequently received pulses of luteinizing hormone-releasing hormone (LHRH) or saline solution during the expected surge period. Two other groups were fed methallibure to pharmacologically suppress the oestradiol benzoate-induced LH surge. In addition, one of these groups was given pulses of an LHRH agonist (LHRH-A) during the surge period. Within 2 h of the start of pulsatile LHRH infusion, LH increased in sesame oil-treated gilts, but not in oestradiol benzoate-treated gilts, suggesting that the pituitary responsiveness to LHRH in immature gilts is decreased by oestrogen before the onset of the LH surge. Pulsatile LHRH infusion did not enhance the amplitude of oestradiol benzoate-induced LH surges nor did it advance its onset. Feeding methallibure suppressed the oestradiol benzoate-induced LH surge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501711 TI - Relationship between ovulation rate and concentrations of insulin-like growth factor-1 in plasma during the oestrous cycle in various genotypes of sheep. AB - To determine whether concentrations of insulin-like growth factor-1 (IGF-1) in blood of ewes change during the oestrous cycle, oestrus was synchronized for 45 ewe lambs from four genotypes (Finn ewes selected for low ovulation rate (LF), Finn ewes selected for high ovulation rate (HF), unselected control Finn ewes (CF) and Cambridge ewes (CAM)) using progestin sponges and blood samples were taken every day from day 0 (day 0 = day of progestin sponge removal) to day 5, and then every second or third day until 3 days after the next oestrus. Ovulation rates (determined via laparoscopy) following the first oestrus were 1.3, 3.3, 2.0 and 2.1 for LF, HF, CF and CAM groups, respectively. In a second experiment, jugular and utero-ovarian venous blood samples were collected simultaneously from seven Rambouillet crossbred ewes during the mid-luteal phase of an oestrous cycle to determine whether the ovary is a major source of blood IGF-1. In the first experiment, plasma IGF-1 concentrations increased (P < 0.05) between days 0 and 3, and then decreased (P < 0.05) between days 4 and 8 in all groups. IGF-1 concentrations increased again at the subsequent oestrus. There was no significant difference in plasma IGF-1 between HF and LF ewe lambs. Overall, plasma IGF-1 was lowest (P < 0.05) in CAM and highest in CF ewe lambs at all stages. Plasma IGF-1-binding protein activity did not vary with stage of cycle or differ (P > 0.10) among genotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501712 TI - Influence of oxytocin removal from the corpus luteum on secretory function and duration of the oestrous cycle in cattle. AB - Mature heifers (n = 31) were infused with either saline or noradrenaline (0.3 microgram kg-1 min-1) via a cannula inserted into the aorta abdominalis through the coccygeal artery (cranial to the origin of the ovarian artery). Noradrenaline was infused for three periods of 30 min on days 11 and 12 and on days 15 and 16 of the oestrous cycle. After the noradrenaline treatment, saline was given for 1 h in the same way. During each infusion, peripheral blood samples were collected for progesterone and oxytocin determination every 5-10 min and then once a day until oestrus. As a control, four heifers were infused with saline in latin square design on days 11, 12 and on days 15, 16; they were bled once a day until oestrus. Other heifers were infused on the same days, but 1 h after the last infusion of noradrenaline, 500 micrograms of prostaglandin F2 alpha (PGF2 alpha) analogue was injected, to measure any remaining luteal oxytocin. For comparison four heifers were injected with PGF2 alpha analogue alone on day 12 and four others on day 16. Blood samples were taken as described previously. Each infusion of noradrenaline stimulated (P < 0.01) progesterone secretion. There was a significant (P < 0.05) response of oxytocin to each noradrenaline stimulation on days 11 and 12, although on each day the response to the second infusion was reduced and further reduced after the third infusion. On days 15 and 16, only the first noradrenaline infusion caused a clear surge of oxytocin with much smaller increases in oxytocin secretion after subsequent infusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501713 TI - Age-related changes in blood concentrations of FSH, LH and testosterone and testicular morphology in a new rat sterile mutant with hereditary aspermia. AB - A new rat mutant showing aspermia was investigated. Groups of 4-7 mutant male rats were killed at 3, 5, 10, 15 and 25 weeks of age. Examination by microscope showed apparent abnormalities in the seminiferous epithelium from 3 weeks of age onward. Inclusion-like bodies were observed in the cytoplasm of pachytene spermatocytes from 3 weeks old and instead of spermiation, polynuclear giant cells were formed within the seminiferous epithelium after 5 weeks of age. Histological analysis of seminiferous epithelium of adult mutant rats also showed a marked decrease in the number of preleptotene, leptotene and pachytene spermatocytes and tubules containing only spermatogonia and Sertoli cells in the seminiferous epithelium increased with age. However, the combination of other cellular elements of germ cells in the seminiferous epithelium was similar to that in normal rats and the distribution rate of these seminiferous tubules was close to that of normal rats, indicating that cyclicity of seminiferous epithelium was still maintained in the mutant rats despite the lack of spermiation. Plasma concentrations of FSH and LH were significantly higher in the mutant male rats than in normal male rats at 5 and 10 weeks of age onward, respectively. Plasma concentrations of testosterone were lower in the mutant male rats than in normal male rats. Silastic capsules containing testosterone were implanted into the unilateral testis of adult mutant male rats and animals were autopsied 5 weeks later. However, intratesticular administration of testosterone did not affect restoration of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501714 TI - FSH-stimulated follicle development in ewes in high and low body condition and chronically treated with gonadotrophin-releasing hormone agonist. AB - Ovarian follicle development in response to FSH infusion was investigated in Scottish Blackface ewes with high and low body condition scores in which endogenous gonadotrophin secretion and follicle development to > or = 2.5 mm diameter was suppressed using subcutaneous implants containing a GnRH agonist. In two experiments conducted during the normal breeding season, groups of 20 (Expt 1) and 15 (Expt 2) ewes were fed to achieve body condition scores > or = 2.75 (high; H) or < or = 1.75 (low; L). In both experiments GnRH agonist implants were inserted four weeks before FSH was infused for 72 h at 7 micrograms h-1 to group H animals or at 5 micrograms h-1 to group L animals; the infusion rates were designed to ensure similar circulating FSH concentrations in animals of both groups. In Expt 2, additional subcutaneous implants containing oestradiol were inserted 21 days after insertion of GnRH agonist implants and 7 days before the FSH infusion began. In both experiments, FSH infusion was associated with an increase in circulatory concentrations of LH (P < 0.01) and FSH (P < 0.001), but there was no difference with body condition in mean circulating gonadotrophin concentrations, the numbers of ovarian follicles > or = 2.5 mm diameter, the proportion of these follicles that were oestrogenic or the mean rate of oestradiol secretion in vitro. It is concluded that differences in body condition of ewes do not affect the responsiveness of the ovary to FSH, in the presence or absence of oestradiol, as measured by the number, size and steroidogenic capacity of ovarian follicles present following FSH infusion. PMID- 8501715 TI - Relationship between prostaglandin-induced luteolysis and temporary inhibition of myometrial activity in late pregnant cows with ear implants containing progestagen. AB - The influence of luteolysis on myometrial activity in late pregnant cows was studied by measuring electromyographic (EMG) activity and concentrations of progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) in maternal arterial plasma of five cows. Application of two ear implants containing progestagen at day 261 of gestation was followed by an injection of a luteolytic dose of a prostaglandin F2 alpha (PGF2 alpha) analogue (PG) on day 264. Calving was initiated by removal of the implants and a single injection of 5 mg flumethasone on day 270. All calves were born alive at a mean interval of 36 h. After 4 h of hyperactivity immediately following the injection of PG, myometrial activity was almost completely absent for 20 h; before luteolysis the total duration of EMG activity was 7.21 +/- 0.31 min h-1 (mean +/- SEM), during the 4 h after PG 23.61 +/- 3.40 min h-1, and during inhibition 2.70 +/- 0.87 min h-1. After the last period, EMG activity recurred and reached values of 14.52 +/- 3.07 and 11.17 +/- 2.87 min h-1, on days 265 and 269, respectively. Concentrations of progesterone in maternal plasma decreased from 4.17 to 1.14 ng ml-1 within 12 h after PG, whereas concentrations of PGFM in plasma remained low, varying from 15 to 30 pg ml-1. After removal of the implants and injection of flumethasone on day 270, EMG activity increased without an inhibitory phase and reached maximum values around the time of expulsion of the calves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501716 TI - Fine structure of the sperm storage tubules in the box turtle oviduct. AB - The sperm storage tubules of the box turtle (Terrapene carolina) were examined by transmission electron microscopy. Tubules containing spermatozoa were surrounded by 6-8 secretory cells, each of which contains numerous membrane-bound vesicles presumably containing precursors to egg white proteins. The apical membranes of these cells contain microvilli, and the apical lateral membranes possess prominent junctional complexes. Cells comprising the spermatozoa-containing tubules cannot be differentiated from those devoid of spermatozoa. Various quantities of spermatozoa reside free in the lumina of the secretory tubules, and are not in contact with host cells. Only the presence of ducts communicating with the oviduct lumen serve to differentiate the spermatozoa-containing tubules. PMID- 8501717 TI - Hormonal and photoperiod-induced changes in testicular interleukin-1-like factor in bank voles, Clethrionomys glareolus. AB - Testicular interleukin-1-like factor (tIL-1) is a cytokine secreted presumably by Sertoli cells in several mammalian species. The function of this cytokine is unknown: tIL-1 may control meiosis, act as a mitogen for spermatogonia or have both of these functions. The present investigation was conducted to assess tIL-1 activity and its hormonal control in a seasonally breeding photoperiodic mammal during testicular maturation and photoperiod-induced regression. Testicular maturation in long photoperiod (20 h light:4 h dark) was accompanied by the appearance of tIL-1 activity at the age of 32-39 days which increased as full sexual maturity was reached. No significant tIL-1 activity was detected when pubertal development was inhibited or testicular regression induced by subjecting juvenile and adult bank voles to a short photoperiod (6 h light: 18 h dark) for 6 to 8 weeks. Administration of human chorionic gonadotrophin (hCG; 60 IU kg-1) increased tIL-1 activity in sexually mature as well as regressed testes. In the photoregressed voles FSH (1.2 U kg-1) administration, which induced a three-fold increase in testicular weight and stimulated spermatogenesis, did not induce detectable concentrations of tIL-1. Administration of FSH followed by hCG increased tIL-1 activity significantly in the atrophic testis, but this was probably due to hCG, since FSH treatment alone was without effect. In conclusion, in accordance with the proposed role of tIL-1 as a germ-cell mitogen and a meiosis-promoting factor, tIL-1 activity correlated positively with spermatogenic activity during testicular maturation and photoperiod-induced regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501719 TI - In vitro fertilization and embryo development in the marmoset monkey (Callithrix jacchus). AB - Oocytes aspirated from preovulatory (i.e. > or = 2 mm) follicles of marmoset monkeys were graded for maturity according to the degree of cumulus expansion, grade I being most mature and grade IV least mature. After preincubation for 2-5, 9-11 or 21-29 h, 82% of oocytes could be fertilized using epididymal spermatozoa and only 2.3% were polyspermic. Fertilization rate was lowest (60%) in grade IV oocytes and all oocytes preincubated for 2-5 h (53%). Fertilization rate increased to 92% in oocytes preincubated for 21-29 h. Embryos developed in vitro to a mean of eight cells. Embryo development was unaffected by oocyte maturity but correlated with preincubation time. Oocytes preincubated for 2-5 h developed into embryos with significantly fewer cells than those preincubated for 9-11 or 21-29 h (P < 0.001). Fifty-six per cent of embryos showed delayed cleavage and these had fewer cells than non-delayed embryos (P < 0.001). When oocytes were preincubated for 2-5 h, development of all resulting embryos was delayed. However, only 17 and 58% of embryos developing from oocytes preincubated for 9-11 and 21-29 h, respectively, were delayed and this was independent of oocyte maturity. PMID- 8501718 TI - Comparisons of endocrinology and behavioural events during the periovulatory period in Meishan and large-white hybrid gilts. AB - Attainment of puberty, cycle lengths, ovulation rate and endocrinology during the periovulatory period were studied in Meishan (MS) and European Large-White hybrid (LW) gilts. The mean age at onset of puberty of 115 days in MS (n = 20) gilts was younger (P < 0.001) than the 235 days in LW (n = 23). In the MS population studied, ovulation rate was not different (P > 0.1) during the third and fourth oestrous cycles, nor were there differences (P > 0.1) in the mean cycle length over the first three cycles. Overall changes in plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol did not differ significantly (P > 0.1) between the breeds (MS, n = 6; LW, n = 5) during the periovulatory period, but plasma inhibin concentrations were significantly (P < 0.05) higher in the MS. The time intervals from the oestradiol peak concentration and the onset of the LH surge until the onset of behavioural oestrus were significantly different (P < 0.005) between the breeds, with oestrus occurring earlier in the MS. However, no difference (P > 0.1) was found between the groups when the intervals from the peak oestradiol concentration to the onset of the LH surge were compared. These results indicate differences between the breeds, particularly in terms of the age of attainment of puberty and the timing of the onset of behavioural oestrus relative to the oestradiol and LH surges. PMID- 8501720 TI - Pregnancy after subzonal insemination with spermatozoa lacking outer dynein arms. AB - The absence of outer dynein arms in the sperm flagellum induces an abnormal movement pattern associated with male infertility. These spermatozoa can decondense in zona-free hamster oocytes but result in a very low fertilization rate in in vitro fertilization. We hypothesized that subzonal insemination could help achieve fertilization and pregnancy. A randomized prospective trial (five couples, five cycles) comparing subzonal insemination (n = 31 oocytes) and routine IVF (n = 23 oocytes) was carried out. Oocytes were microinjected with 8.5 +/- 3.6 spermatozoa. In a second series (nine cycles), all the oocytes were microinjected with 10.5 +/- 4.3 spermatozoa. In the randomized series, the fertilization rate was 16.1% without polyploidy, whereas no fertilization was obtained after control IVF insemination. In the second series involving nine couples, six of whom were included in the first series, the fertilization rate increased to 57.8% with a 27.8% polyspermic rate. Eighty-eight per cent of the zygotes cleaved normally (29 out of 33). A total of 11 embryo transfers resulted in three pregnancies, one of which terminated one month later, a second being ongoing and the third delivering a healthy girl. A 21.4% pregnancy rate per cycle, with a 37.5% pregnancy rate per couple, justifies the use of subzonal insemination to treat this particular flagellar dyskinesia. PMID- 8501721 TI - Increased testis growth and sperm production in adult rats following transient neonatal goitrogen treatment: optimization of the propylthiouracil dose and effects of methimazole. AB - Treatment of male rat pups with the reversible goitrogen 6-propyl-2-thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth to day 25, increases their testis size and daily sperm production (DSP) at 160 days of age by up to 80% and 140%, respectively. The purpose of this study was to examine the effectiveness of various concentrations of PTU and determine the PTU dose that would maximize testis growth while minimizing side effects such as decreased maternal water consumption and decreased pup growth. Whether this effect was specific to PTU was determined by evaluating the effects of another commonly used goitrogen, methimazole (MMI), in increasing adult testis size and sperm production. Dams were given PTU (0.1-0.0004% w/v) or 0.025% MMI (w/v) in their water from birth to day 25 post partum, then given no further treatment. Thyroxine concentrations were measured in all groups of pups at 25, 35 and 45 days, and testis weight and DSP were determined at 90 days of age. At 25 days of age, thyroxine concentrations were maximally decreased by PTU treatments of 0.0015% or greater; less severe decreases were produced by 0.0004% PTU or 0.025% MMI. Thyroxine concentrations increased in all treated groups at day 35 compared with day 25, and returned to normal by day 45. At 90 days of age, testis weight was increased by about 40% in rats whose mothers had been treated with doses of 0.006% PTU or greater, whereas testis weights in groups given 0.0015 and 0.0004% PTU or 0.025% MMI were increased 31, 15 and 18%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501722 TI - Changes in frequency and force production of the human myometrium with alteration of pH and metabolism. AB - Changes in uterine metabolism and intracellular pH occur with uterine activity and these may in turn alter function. We have investigated the effects of changes in intracellular pH and metabolic inhibition on the spontaneous activity of isolated nonpregnant and pregnant human myometrial strips at 37 degrees C. Intracellular alkalinization resulted in a marked increase in the frequency of contractions in both nonpregnant and pregnant preparations. Intracellular acidification reduced force production in pregnant and nonpregnant preparations. The effects of pH were concentration dependent. Metabolic inhibition (2 mmol cyanide l-1) abolished spontaneous contractions in nonpregnant preparations (ten of ten) but pregnant preparations were able to maintain activity, although at a reduced level (eleven of fifteen). Possible mechanisms involved and relevance to uterine dysfunction are discussed. PMID- 8501723 TI - Early hypophysectomy of sheep fetuses: effects on growth, placental steroidogenesis and prostaglandin production. AB - The factors involved in the control of steroid secretion from the ovine placenta and in fetal growth are as yet unclear. We hypothesized that factors derived from the fetal pituitary may play a role in the production and release of placental steroids and in growth of the fetus, and have investigated the effects of fetal hypophysectomy performed between day 70 and day 79 of gestation (term = 147 days) on systemic concentrations of hormones derived from the placenta, and on fetal growth. Maternal peripheral progesterone, placental lactogen and uterine vein progesterone increased significantly from day 90 in all ewes. Peripheral concentrations of prostaglandin E2 and peripheral and uterine vein oestrone sulfate increased significantly in the control group but not in the fetal hypophysectomy group. Uterine vein prostaglandin E2 increased significantly after day 95 in the control group and after day 105 in the fetal hypophysectomy group. Early fetal hypophysectomy caused marked growth retardation. The weights of the brain, kidneys and liver of hypophysectomized fetuses were the same as those of controls suggesting that their growth is not under pituitary control. In contrast, the weights of heart and lungs were reduced in proportion to body weight, suggesting that heart, lung and carcass growth were under pituitary control. Our data indicate that the fetal pituitary influences the control of placental steroid and prostaglandin E2 biosynthesis after day 90 of gestation in sheep, but that output of other hormones such as placental lactogen is independent of pituitary control, and may determine organ-specific growth parameters that are unaffected by removal of the fetal pituitary. PMID- 8501724 TI - Compartmentalized reactivity of M3/38 (anti-Mac-2) and M3/84 (anti-Mac-3) in the uterus of pregnant mice. AB - Changes in the expression of antigens on mouse uterine or embryonic tissues were examined by enzyme immunocytochemistry. Cryostat sections of uteri from days 1, 8 and 15 of pregnancy were probed with the monoclonal antibodies M3/38 and M3/84, originally defined by their reactivity with macrophage surface antigens (Mac-2 and Mac-3, respectively). In the uterus of pregnant mice, reaction of these antibodies was not limited to leucocytes. M3/38 did not react at detectable levels with cells in the uterus on day 1 but did react with decidual cells immediately surrounding the embryo on day 8. By day 15, the placenta, decidua basalis and metrial gland were intensely positive but the embryo was negative. M3/84 reacted with the luminal side of the endometrium on day 1, the entire decidual mass on day 8, and with all maternal and fetal tissues on day 15. M3/38 was detected in saline-soluble preparations of uterine tissue and had a molecular mass of approximately 32-35 kDa as determined by SDS-PAGE and western blot analysis. The pattern of expression of these molecules suggests a functional relationship to developmental changes that occur at the maternal-fetal interface. PMID- 8501725 TI - Activity of phospholipase C and release of prostaglandin F2 alpha by endometrial tissue from ewes during the oestrous cycle and early pregnancy. AB - Oxytocin appears to play an important role in regulating uterine secretion of prostaglandin F2 alpha (PGF2 alpha) in sheep. Changes in uterine secretion of PGF2 alpha throughout the oestrous cycle and early pregnancy may be due to changes in the intracellular regulatory pathways that control synthesis of PGF2 alpha in response to oxytocin. In this experiment, caruncular endometrial tissue was collected from ewes throughout the oestrous cycle and early pregnancy. Endometrial tissue was incubated in vitro to assess release of PGF2 alpha and activity of phospholipase C (PLC) in response to oxytocin. Release of PGF2 alpha in the presence of arachidonic acid was used to assess the activity of prostaglandin H2 endoperoxide synthase (PGS). In non-pregnant ewes, oxytocin stimulated release of PGF2 alpha from endometrial tissue collected on days 14 and 16, but not on days 4-7, 10 or 12 after oestrus. This coincided with times when oxytocin stimulated the activity of PLC. Release of PGF2 alpha was enhanced by the addition of arachidonic acid to tissues collected on days 12, 14 and 16 after oestrus. As with tissue from nonpregnant ewes, oxytocin could stimulate release of PGF2 alpha on days 14 and 16 of early pregnancy. Yet, oxytocin had no effect on activity of PLC in tissue from pregnant ewes. Release of PGF2 alpha in the presence of arachidonic acid by tissue from pregnant ewes was similar to that in nonpregnant ewes at comparable times after oestrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501726 TI - Immunohistochemical expression of tumour-associated glycoprotein and polymorphic epithelial mucin in the human endometrium during the menstrual cycle. AB - An epitope defined by a second generation murine monoclonal antibody (LU-BCRU-G7) produced against a breast tumour-associated fucosylated glycoprotein of M(r) 230,000 was found to exhibit phase specific reactivity in human endometrium during the menstrual cycle. Distribution and cycle related expression of the LU BCRU-G7 determinant was different from the staining patterns observed with antibodies that react with the polymorphic epithelial mucins, HMFG 1 and NCRC 11, as determined by immunohistochemistry. Initial expression of the LU-BCRU-G7 determinant was associated with the peri-basal region of glandular epithelial cells with maximal staining during the mid-secretory phase. Diffuse cytoplasmic staining was also observed from day 10 to day 26, with a marked increase in the early secretory phase. Reactivity of NCRC 11 also showed maximal expression in the midsecretory phase with no reactivity detected in early and mid-proliferative phases. The HMFG 1 defined epitope exhibited the opposite pattern of expression with maximal reactivity in the proliferative phase and little or no reactivity in the secretory phase. These findings suggest that expression of the LU-BCRU-G7, HMFG 1 and NCRC 11 defined determinants in the human glandular epithelium of the endometrium is differentially hormonally regulated, and may be of value as markers for endometrial function. PMID- 8501729 TI - Segmental distribution of alpha-glucosidase, ornithine decarboxylase and polyamines in the human epididymis. AB - Regional differences in the total activities of the epididymal secretory parameter, alpha-glucosidase, were demonstrated in the 20,000 g supernatants of human epididymal homogenates. A comparison of the enzymic activities in the supernatants and the washings from 12 one centimetre segments of human epididymides indicated an activity peak in segments 3-4 which appeared to be largely intracellular and which presumably reflects the acidic isoenzyme. A second peak in the caudal region, the segmental localization of which was more variable and differed in post-mortem and operation specimens, appeared to be primarily intraluminal. The activities of ornithine decarboxylase (ODC), the rate limiting enzyme in the polyamine pathway, also exhibited regional differences with higher activities in relatively short segments in both caput and caudal portions. Corresponding alterations were also found in the tissue concentrations of the enzyme products, spermidine and spermine. The increased intracellular activities of ODC and alpha-glucosidase in the distal caput segments presumably reflect the transition of epithelium from the efferent to the epididymal ducts. PMID- 8501730 TI - Unexplained infertility. AB - Unexplained infertility is a nebulous diagnosis that is justified only after a thorough and meticulous investigation of both partners. Even if the five basic tests constituting the infertility investigation have not revealed an abnormality, there may be a specific cause. Diagnosing unexplained infertility in this setting is somewhat arbitrary. In such couples, spontaneous pregnancies have been reported, with an average cumulative pregnancy rate of 60% after three years. Some additional testing, however, is appropriate. Treatment of unexplained infertility, however, tends to be empiric if no cause is found. Our current therapeutic plan entails superovulation with intrauterine insemination for at least four cycles. A cycle fecundity in the range of 0.23 may be expected but is highly influenced by the woman's age, with cycle fecundity dropping to as low as 0.05 after age 40. Alternatives to superovulation and intrauterine insemination are direct intraperitoneal injection of sperm with or without oocytes and intrafollicular injection of sperm. Gamete intrafallopian transfer and in vitro fertilization (IVF) are appropriate after a trial of empiric therapy. Our preference is to carry out IVF because the knowledge that fertilization has occurred is important in that fertilization failure is a known cause of unexplained infertility. PMID- 8501727 TI - Comparison of different antibody-conjugate derivatives for the development of a sensitive and specific progesterone assay. AB - Antibodies raised against progesterone with hormone-carrier protein bridges placed at four different carbon positions were used to compare the sensitivity and specificity of homologous and heterologous enzyme-hormone conjugates. All heterologous assays were at least twice as sensitive as the corresponding homologous assays. The best results were obtained by using antibodies against 7 alpha-carboxyethyl-thioether-progesterone with 6 beta-hemisuccinate-progesterone conjugate (or hemimaleate). The sensitivity with human sera was 0.25 ng ml-1 and, the highest crossreaction 10% with 5 beta-pregnane-3,20-dione, and reproducibility, recovery and accuracy were satisfactory. The correlation coefficient with radioimmunoassay in 103 human sera tested was r = 0.915. The assay was successfully applied for the diagnosis of pregnancy in dairy cattle. PMID- 8501728 TI - Effects of pregnancy and lactation on plasma lipid and lipoprotein concentrations, lipoprotein composition and post-heparin lipase activities in Shetland pony mares. AB - The incidence of hyperlipaemia in ponies is highest in mares in late gestation and then early in lactation. Plasma lipid and lipoprotein concentrations were measured to establish the metabolic basis for this and the lipoprotein composition of six healthy Shetland ponies was analysed before pregnancy, in the last six weeks of gestation and one month after foaling. In the pregnant ponies, the concentrations of cholesterol and triglyceride were significantly increased (both P < 0.05) because of increased concentrations of high density lipoproteins (HDL) and very low density lipoproteins (VLDL), respectively (both P < 0.05). The VLDL were significantly enriched in triglyceride and depleted of protein (P < 0.05 in each case), with the majority of cholesterol in the free rather than esterified form. These changes appeared to reflect increased hepatic triglyceride synthesis and VLDL secretion because the activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were unaltered. After foaling, the concentrations of triglyceride and VLDL decreased significantly (both P < 0.05) because of increased lipoprotein lipase activity consistent with the induction of the enzyme in mammary tissue to provide for milk fat synthesis. Plasma cholesterol and HDL concentrations remained high and non-esterified fatty acid concentrations were significantly increased (P < 0.05). The VLDL remained enriched in triglyceride but had normal cholesterol and protein compositions, although the mass of phospholipids was reduced. The changes in plasma VLDL concentration and composition found in the pregnant ponies mimicked those previously reported in ponies with hyperlipaemia and suggested a metabolic basis for the incidence of the disease in late gestation. PMID- 8501732 TI - In vitro fertilization and other assisted reproductive techniques. AB - Each year, thousands of pregnancies are achieved worldwide by in vitro fertilization (IVF) and its modifications, commonly grouped under the general term "assisted reproductive techniques" (ARTs). The IVF program at the University of Southern California (USC) was among the first to be established in the United States and had the distinction of achieving success, in 1981, with the first IVF infant to be born on the West Coast. This paper discusses patient selection, superovulation techniques, methods of follicle aspiration, sperm preparation, embryo transfer procedures and management of the luteal phase of ART cycles. The various ARTs are described, as are the expected success rates. Particular emphasis is placed on the techniques of oocyte donation and unstimulated IVF, both of which play prominent roles in the treatment of infertility in the USC program. PMID- 8501731 TI - Recurrent abortion. AB - Recurrent spontaneous abortion affects about 0.5% of women. The causes of recurrent abortion are fetal and maternal. Most fetal causes are genetic or chromosomal abnormalities. Most maternal causes are congenital or acquired uterine abnormalities. Controversy exists regarding the possible etiology of immunologic factors and lupus anticoagulant activity as causes of recurrent abortion. Performance of histocompatibility locus antigen typing and immunotherapy do not appear to be cost effective or necessary in couples with recurrent abortion. The use of treatment for the presence of lupus anticoagulant or anticardiolipin antibodies has not been found to be superior to no treatment and must be regarded as investigational. PMID- 8501733 TI - Investigation of the female pelvis. AB - Abnormalities of the female pelvis are commonly discovered in the evaluation of infertile couples. A systematic approach to diagnosing pathology requires the careful integration of both noninvasive and invasive testing. Transvaginal ultrasound imaging provides immediate and detailed information regarding the gross anatomy of the pelvis and is both a highly sensitive and specific test when used by skilled observers. Hysterosalpingography remains a helpful adjunct in discovering more subtle abnormalities, such as endometrial polyps and salpingitis isthmica nodosa. Invasive surgical tests are hysteroscopy and laparoscopy. These methods accurately define pathology, and in many cases pelviscopic instruments may be employed as a means of delivering surgical treatment. A systematic approach should be used for evaluating the female pelvis, taking into consideration the rationale behind utilizing various diagnostic procedures. PMID- 8501734 TI - Resident training in a multidisciplinary breast clinic. AB - A multidisciplinary breast clinic was initiated at William Beaumont Army Medical Center involving resident and staff physicians from the Departments of Obstetrics and Gynecology, General Surgery, Radiology and Pathology. During the period August 1988 to May 1989, 2,186 mammograms (MOGs) were screened. For this report, 197 patients were evaluated. Of them, 187 patients had been referred to the breast clinic based on MOG findings. Pathologic specimen correlation with the mammograms was performed on a periodic basis. Thirty-four patients were biopsied based on either physical examination or MOG findings. Biopsy diagnoses included: normal tissue (1), fibrocystic disease (18), sclerosing adenosis (1), fibroadenoma (8), mastitis (1) and intraductal carcinoma (5). The Multidisciplinary Breast Clinic provided improved care through expedited patient management. Resident training was accomplished through refinement of examination and diagnostic skills, management of abnormal MOGs, needle aspiration of breast masses and improved communication between the different medical disciplines. PMID- 8501735 TI - How to critically evaluate positions on obstetric ethics. AB - We identify three tools for the critical evaluation of positions on obstetric ethics. The first is the distinction between descriptive and normative obstetric ethics. The second comprises the "Six Cs" of rigorous ethical analysis and argument: clarity, consistency, coherence, clinical applicability, clinical adequacy and completeness. The third is the avoidance of pitfalls that might arise from failing to acknowledge the inherent limitations of fields that contribute to normative obstetric ethics: law, region, professional consensus, uses of authority and philosophy. PMID- 8501737 TI - Analysis of factors determining the selection of repeated cesarean section or trial of labor in patients with histories of prior cesarean delivery. AB - We investigated the motivation behind procedures in 241 patients with prior cesarean births; 120 had elective repeat cesarean sections and 121 had vaginal birth after cesarean section (VBAC). Patients were of similar age, gravity and parity, but significantly more patients in the repeat cesarean group had their initial surgery because of failure to progress in labor; significantly more patients in the VBAC group had their initial cesarean section because of fetal distress. The main factors behind the decision to attempt VBAC were patient's desire (81.0%), patient's desire and physician's advice (12.4%) and physician's advice (6.6%). The main factors behind the decision to have repeat cesarean sections were medical or obstetric indication (45.8%), patient's desire (31.6%), patient's desire and physician's advice (9.1%) and physician's advice (13.3%). We conclude that it will be difficult to substantially decrease the present rate of repeat cesarean births, and that preventive efforts should be directed toward decreasing the incidence of primary cesarean deliveries. PMID- 8501736 TI - Endocervical brush versus cotton swab for obtaining cervical smears at a clinic. A cost comparison. AB - Use of the nylon endocervical brush has been shown to increase the proportion of Papanicolaou smears with endocervical cells in a variety of populations. Each endocervical brush is approximately 100 times more expensive than the cotton swab that has been used routinely for cervical cytology collection. We sought to determine prospectively whether the endocervical brush would be cost effective by reducing the need for repeat sampling due to Papanicolaou smears' lacking endocervical cells. Cervical cytology specimens showed no endocervical cells in 114 (20%) of 561 women sampled with a cotton swab and Ayre spatula. In contrast, 37 (7%) of 511 women sampled with the endocervical brush and Ayre spatula had no endocervical cells in their specimens. A cost analysis showed that at our clinic, where approximately 3,300 Papanicolaou smears are performed annually, annual savings of > $22,000 would be realized by use of endocervical brushes. PMID- 8501738 TI - The incidence of adynamic ileus in postcesarean patients. Patient-controlled analgesia versus intramuscular analgesia. AB - With the current clinical popularity of patient-controlled analgesia pumps (PCAP) in postoperative pain management, it is prudent to be aware of the possible risk of adynamic ileus formation from intravenous narcotic administration. We hypothesized that prolonged PCAP exposure could delay bowel motility and increase post-operative morbidity. After stringent exclusionary parameters were met, we retrospectively analyzed 170 postcesarean patients who received PCAP medication and compared data with 171 postcesarean patients who received traditional intramuscular (IM) administration. The degree of adynamic ileus formation of moderate and severe intensity was higher in PCAP users (21.8%) vs. IM users (13.5%), P = .02. There was no significant difference in the average cumulative amount of analgesic administered during the first 24 postoperative hours for PCAP (442.2 mg) vs. IM (397.7 mg), reflecting that the mode of narcotic delivery is responsible for ileus formation rather than the dosage. Type of postoperative diet and speed of diet advancement were also factored into the analysis and did not statistically influence the results. We conclude that PCAP usage may increase the morbidity risk for adynamic ileus formation, and that usage should be accompanied with close monitoring of bowel motility. PMID- 8501739 TI - Suboptimal progesterone production in pathologic pregnancies. AB - Serum progesterone (P) levels were determined at the time of routine prenatal registration (227 patients) or upon presentation for evaluation of vaginal bleeding and/or abdominopelvic cramping/pain (135 patients). P associated with a normal intrauterine gestation was 24.63 +/- 4.19 (SD) ng/mL as compared with 6.29 +/- 2.43 ng/mL and 6.02 +/- 2.39 ng/mL for spontaneous abortions and ectopic gestations, respectively. Further, P differed between asymptomatic (11.92 +/- 9.61 ng/mL) and symptomatic patients (4.81 +/- 3.92 ng/mL) who were subsequently shown to have an abnormal gestation. By establishing a P cutoff point of < or = 14.2 ng/mL and < or = 10.5 ng/mL in asymptomatic and symptomatic patients, respectively, 100% screening sensitivity was reached, and therefore no abnormal gestations would escape detection in our study population. P was either in the normal or abnormal range as early as four weeks' estimated gestational age and persisted as such through the luteal-to-placental shift and up to the time of pregnancy loss or 12 weeks' estimated gestational age. Although there was no significant correlation between P and chorionic gonadotropin levels and pregnancy outcome, the binding constant for native chorionic gonadotropin was 15-52 times lower in 12 of 41 cases of spontaneous abortion but not ectopic gestation, suggesting a possible molecular basis for suboptimal P production. P is therefore an excellent adjunctive marker for prediction of early pregnancy outcome, and in some cases qualitative abnormalities in chorionic gonadotropin may dictate its production. PMID- 8501740 TI - Diabetic ketoacidosis in pregnancy resulting from insulin pump failure. A case report. AB - Ketoacidosis remains one of the most serious complications that can occur in the pregnant diabetic. A 36-year-old class D diabetic presented at 35 weeks' gestation with signs and symptoms of diabetic ketoacidosis. The etiology of her ketoacidosis was insulin pump malfunction. The normal physiologic changes associated with pregnancy placed the woman at increased risk for the development of ketoacidosis. The development of ketoacidosis is a well-known complication of insulin administered via pregnancy. We recommend that the insulin pump be used in selected patients in whom close surveillance can be maintained. PMID- 8501741 TI - Laparoscopic diagnosis of puerperal ovarian vein thrombophlebitis. A case report. AB - Puerperal ovarian vein thrombophlebitis is a relatively rare postpartum complication that may result in serious complications. The syndrome may be diagnosed through exploratory surgery or diagnostic imaging, although the best method remains unclear. In one case, open laparoscopy yielded a swift diagnosis and ensured prompt treatment without necessitating further diagnostic studies. PMID- 8501743 TI - Unilateral twin ectopic pregnancy managed by operative laparoscopy. A case report. AB - An unusual case of unilateral twin ectopic pregnancy occurred. The patient was managed successfully by operative laparoscopic salpingostomy. PMID- 8501742 TI - Obstetric and anesthetic considerations in the May-Hegglin anomaly. A case report. AB - The obstetric and anesthetic considerations in the management of a patient with the May-Hegglin anomaly, an autosomal dominant platelet deficiency, are discussed. A review of the medical literature notes three previous case reports of May-Hegglin anomaly in pregnancy. In addition to the two successful pregnancies reported in this paper, there are four infant survivors among the five reported pregnancies. Anesthetic managements included general and spinal anesthesia: the latter employed following platelet transfusion. A successful pregnancy should be anticipated when management includes a well-informed patient and coordinated obstetric and anesthetic care. PMID- 8501744 TI - Metabolic bone status in young women with juvenile chronic arthritis. AB - A group of 26 young women (18-36 years of age) with juvenile chronic arthritis (JCA, duration 8-33 years) was investigated for bone metabolism and mineral status. Six of the patients were receiving longterm corticosteroid therapy, and 5 had received corticosteroid treatment in the past. Serum osteocalcin and urinary hydroxyproline were significantly elevated in 17 and 14 of the 26 patients, respectively, compared with healthy controls. Compared to controls, bone mineral density (BMD) in the lumbar spine was significantly lowered in 6 of 26 patients, all of whom were in the corticosteroid treated subgroup. No correlation was evident between any of the variables measured, except for the association of corticosteroid therapy with low BMD. PMID- 8501745 TI - HLA class II alleles in juvenile dermatomyositis. AB - HLA class II alleles were investigated in 27 Czech patients (11 females and 16 males) with juvenile dermatomyositis. The immunogenetic investigation comprised determination of DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 alleles. Their prevalence was compared with that found in healthy Czech controls. No allele was found significantly more frequently in patients than in controls. PMID- 8501746 TI - Juvenile spondyloarthropathies in 1992. AB - There is some evidence that patients with late onset pauciarticular juvenile chronic arthritis (JCA) should be included among those with spondyloarthropathies, at least during the course of their disease, even if at the onset of the disease we prefer to label them as patients with JCA. The clinical symptoms which could allow us to classify them as spondyloarthritic are frequently absent at the onset of the disease. The gut seems to play a role in the pathogenesis of this form of JCA, though the exact mechanisms must be elucidated further. PMID- 8501747 TI - Prospects in pediatric rheumatology. AB - Although pediatric rheumatology became a specialty during the mid 1970s, a number of clinical, research and therapeutic issues still need to be addressed. New entities need to be clearly defined and definite diagnostic criteria established. Research has identified the involvement of cytokines and genetic factors in juvenile chronic arthritis (JCA), while synthetic histone peptides will allow more thorough research into antinuclear antibodies. No satisfactory drug therapy exists for the treatment of chronic rheumatic disease, though the use of local injections of triamcinolone hexacetonide has modified the prognosis of pauciarticular JCA. Joint replacement requires special consideration, as prostheses need to be constructed according to individual requirement. Finally, the psychological impact of JCA must not be underestimated. PMID- 8501748 TI - An imaginative approach to synovitis--the role of hypoxic reperfusion damage in arthritis. AB - The rheumatoid joint is hypoxic. The loss of the physiologic defense mechanism, reflex muscle inhibition, allows the generation of high intraarticular pressures, particularly during exercise. Hypoxia alters the biochemistry of the synovium and encourages the production of reactive oxygen species (ROS) on reperfusion of blood. In excess, ROS damage tissues, and the products of oxidative damage are detectable in rheumatoid synovial fluid. In addition to damaging proteins, carbohydrates and lipids, cellular and structural damage also occurs. PMID- 8501749 TI - The place of corticosteroid therapy in juvenile chronic arthritis in 1992. AB - Juvenile chronic arthritis (JCA) is a heterogeneous disease, treated with systemic or local corticosteroid therapy. Systemic corticosteroids are indicated in systemic JCA only when nonsteroidal antiinflammatory drugs have failed or cause side effects or if there is evidence of severe pericarditis. Intravenous pulses of methylprednisolone produce little benefit. Corticosteroid therapy must be tapered slowly, and it may take a long time to reach an alternate day regimen. Side effects are the most worrying problem with daily therapy, particularly growth arrest. Some cases of polyarticular JCA with severe functional impairment and unresponsive to other therapies may benefit from systemic corticosteroids. The most powerful drug for the treatment of joints is triamcinolone hexacetonide, which produces excellent responses in two-thirds of knee joint cases treated. Local corticosteroid therapy is also indicated for chronic iridocyclitis. PMID- 8501750 TI - Problems related to systemic glucocorticoid therapy in children. AB - Glucocorticoids (GC) are among the most potent antiinflammatory agents that can be used in the treatment of rheumatic diseases. Their mechanisms of action are multiple and complex. As would be expected of any drug with a wide range of actions, systemic GC have many side effects, some severe and some of which like growth suppression, are specific to childhood. To prescribe GC with an acceptable incidence of side effects, the following recommendations should be heeded: use only in well established indications, use at the lowest possible dose, as a single, daily administration, or as an alternate day regimen whenever possible, use concomitantly with steroid sparing agents (e.g., NSAID, disease modifying agents in rheumatic diseases (DMARD), antiepileptics) and choose the GC with the fewest side effects. PMID- 8501751 TI - Deflazacort in juvenile chronic arthritis. AB - Vertebral crush fracture associated with glucocorticoid therapy causes major morbidity in juvenile chronic arthritis (JCA). Deflazacort (DFZ) may have an advantage over prednisone (PRED) because of its alleged bone sparing properties. Of 34 children with JCA receiving more than 5 mg PRED/day, 31 completed a 1-year, double blind, randomized, comparative trial of DFZ and PRED. Patient characteristics at trial entry were well matched. DFZ and PRED were prescribed in equivalent amounts. DFZ achieved similar disease control to PRED, and was not associated with untoward effects. Joint counts, hematological indices and biochemical values did not differ between treatment groups initially or during the trial. Bone density trends (velocities) in the lumbar spine were measured using dual photon absorptiometry at 3-monthly intervals and trends in bone and soft tissue growth calculated. Lumbar spine bone growth correlated with indices of somatic growth, with wide ranges in each group. Co-variance analysis showed a significant advantage (p < 0.007) of DFZ over PRED when spinal bone density was compared to body surface area and weight. Children taking DFZ showed less weight gain but similar height gain to children taking PRED. Children with poor or no somatic growth showed significant lumbar bone loss only in the PRED group. Of the children originally treated with PRED; 11 were switched to DFZ after completing the double blind study. Data for 26 children treated with DFZ for 1 year were thus available and confirmed a significantly greater rate of spinal bone growth relative to somatic growth, p < 0.002.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501752 TI - Therapy with a new glucocorticoid: effect of deflazacort on linear growth and growth hormone secretion in renal transplantation. AB - In children who have undergone successful renal transplantation, the failure of linear growth, a cushingoid appearance and obesity decrease self-esteem and hamper rehabilitation. Changes in kidney function, growth velocity, weight to height ratio and growth hormone (GH) secretion were studied before, and 2 years after, replacement of methylprednisone (6 +/- 0.3 mg/day; mean +/- SEM) by deflazacort (9.6 +/- 0.5 mg/day) 4 years after renal transplantation in 10 patients aged 9-16 years with stable renal function. Serum creatinine and creatinine clearance did not change significantly during deflazacort treatment. In 8 patients at Tanner stage I, growth velocity increased significantly during the 1st and 2nd year of deflazacort therapy (p < 0.01 and p < 0.005, respectively). Weight to height ratio decreased significantly during the 1st and 2nd year of deflazacort treatment (p < 0.005, p < 0.02, respectively) though in 3 patients, this returned to base levels after 2 years of deflazacort therapy. The mean spontaneous GH secretion increased significantly (p < 0.05). There was a correlation between growth velocity and spontaneous GH secretion during deflazacort therapy. The cushingoid appearance decreased in the majority of patients. Renal function remained stable. PMID- 8501753 TI - Clinical practice in pediatric rheumatology: a review of the Czechoslovak experience. AB - The use of corticosteroid therapy in the treatment of juvenile chronic arthritis in Czechoslovakia is summarized. The indispensability of corticosteroids in pediatric rheumatology is confirmed and some practical aspects of their application are discussed. PMID- 8501754 TI - Future trends in pediatric rheumatology. PMID- 8501755 TI - Sequences of HLA alleles associated with arthritis in adults and children. AB - Adult rheumatoid factor (RF) positive rheumatoid arthritis (RA) and RF positive arthritis of childhood are associated with DRB1*0401 in Caucasians, and DRB1*0405 in Orientals, and in Ashkenazi and nonAshkenazi Jews. Certain other DRB1 alleles (DRB1*0101,1001) which have a similar sequence in the 3rd hypervariable region of the 1st domain are also associated with RA, but they appear to function as weaker risk factors. The difference in the relative strength of the associations is likely to be due to structural differences in the 1st and 2nd variable regions of the first domain of these alleles. Similarities and differences in the HLA associations between North American Caucasoid patients with juvenile arthritis in Dallas, TX, USA, and in Prague, Czechoslovakia, are discussed. PMID- 8501756 TI - Internal organ involvement in juvenile connective tissue disease. AB - Using noninvasive investigative techniques, cardiac, pulmonary and gastrointestinal abnormalities were found in patients with all types of connective tissue diseases. Impedance rheography suggested impaired myocardial function. Abnormalities of pulmonary function included a decrease in diffusing lung capacity for CO (DL) values followed by restrictive ventilatory defects and mild alveolar hyperventilation. The results of endoscopic investigation of the gastrointestinal tract showed inflammatory changes. Ultrasonography revealed dyskinesis of the ducts of the gallbladder and some hepatic and pancreatic structural changes. PMID- 8501757 TI - Heart-lung transplantation for end-stage respiratory disease in cystic fibrosis patients. PMID- 8501758 TI - Population screening in cystic fibrosis. PMID- 8501760 TI - My experience as an adult with cystic fibrosis. PMID- 8501759 TI - Current concepts in physiotherapy. PMID- 8501761 TI - My heart-lung transplant. PMID- 8501763 TI - The role of chemical-induced stress responses in immunosuppression: a review of quantitative associations and cause-effect relationships between chemical-induced stress responses and immunosuppression. AB - Although there is an increasing awareness that drugs and chemicals can modulate the immune system by indirect mechanisms, few compounds have been thoroughly evaluated in this regard. Several environmentally relevant chemicals induce stresslike responses, as indicated by elevated glucocorticoid levels. Comparable glucocorticoid levels induced by physical or psychological stressors are consistently associated with suppression of one or more immunological parameters. Thus, it seems likely that stress-related neuroendocrine mechanisms are important in immunosuppression by some environmental chemicals. Distinguishing direct and indirect (stress-related) mechanisms of immunosuppression is generally possible, and this could be done as a routine part of immunotoxicity assessment. Although it is clear that glucocorticoids can contribute to such immunosuppression, it is also clear that several other neuroendocrine mediators associated with stress responses can be immunomodulatory. Thus, correlation between glucocorticoid levels and immunosuppression does not conclusively demonstrate a cause-effect relationship. Demonstrating such relationships has been difficult, but it has been done in a few cases of drug-induced thymic hypoplasia by monitoring several parameters known to be affected by glucocorticoids and by measuring the ability of a glucocorticoid antagonist (RU 486) or adrenalectomy to block changes in these parameters. A similar strategy might be useful for evaluation of the role of glucocorticoids in drug- or chemical-induced suppression of a variety of immune functions, but the effects of RU 486 on neuroendocrine feedback circuits and the possibility of consequent immunological changes must be considered when the data are interpreted. This approach could also be applied to evaluation of the roles in chemical-induced immunosuppression of other neuroendocrine mediators for which antagonists or agents that block the synthesis or release of the mediator are available. However, it is likely that a comprehensive (and perhaps predictive) understanding of the relationship between chemically induced stress responses and immunosuppression will require more detailed and quantitative elucidation of the mechanisms and regulation of neuroendocrine-immune interactions. PMID- 8501764 TI - Airway constriction by xanthine/xanthine oxidase in guinea pigs in vivo. AB - Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett Rossler method and expressed as a change in ventilation overflow (VO). Inhalation of xanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This airway constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an airway constriction in a concentration-dependent manner (0.1 2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the airway constriction induced by inhaled histamine. However, in SO2-exposed guinea pigs, the inhalation of xanthine/XOD significantly increased the sensitivity to histamine. These results indicate that hydrogen peroxide and other reactive oxygen intermediates produced by xanthine/XOD may cause an airway constriction and airway hyperresponsiveness. PMID- 8501762 TI - Recent advances in cystic fibrosis research. PMID- 8501765 TI - Chronic carbon monoxide exposure in young rats alters coronary vessel growth. AB - The goal of this study was to determine whether chronic monoxide exposure in the developing heart produces long-lasting coronary vasculature alterations. One-day old male rat pups were exposed to 500 ppm CO continuously for 30 d, while littermate controls remained in room air (AIR). At 61 and 110 d of age hearts were removed, perfusion fixed, x-rayed, and processed for analysis of coronary vessel architecture. Body weight (BW) and heart weight (HW) increased with age; the ratio of HW/BW decreased. There were no differences in HW and ventricular dimensions at either age due to prior CO exposure. Morphometric analysis of the fixed hearts from CO-exposed and AIR rats revealed no significant individual group differences in the number of small (27-114 microns) or larger (> 114 microns) vessels in any heart region. The septum (S) in CO rats was an exception: There were more small veins at 61 d of age and more larger veins at 110 d of age. There was a significant increase in the number of small arteries at both ages in the CO rats across all heart regions, and in the smaller veins at 61 d of age. The large vessels in the S at 61 d of age had a significantly greater diameter in CO compared to AIR rats. This was also true for the large arteries in the S and right ventricle (RV) of the 110-d-old rats. Taking all heart regions together, the large arteries in CO rats were larger than in AIR rats. Previous CO exposure significantly increased large artery and total cross-sectional area in the S and RV at 61 d of age, and in RV at 110 d of age. Total cross-sectional area of veins in the S was also increased. Taking all heart regions together, CO significantly increased small artery cross-sectional area at 61 d of age, and small, large, and total artery cross-sectional area at 110 d of age. With one exception (small veins, 110 d of age), there was no effect of CO on vein cross-sectional area. These changes resulted in the percentage of total cross-sectional area contributed by the larger vessels being increased. Pathological examination showed nothing abnormal. The results suggest profound and persistent changes in coronary vessel architecture following chronic neonatal CO exposure. PMID- 8501766 TI - Pulmonary absorption and disposition of [14C]thiophene in rats following nose only inhalation exposure. AB - The absorption, disposition, and metabolism of [14C]thiophene was investigated in rats following nose-only inhalation exposure at 8000 ppm for 1 h. Under these exposure conditions, it was estimated that approximately 16.3% (493 mumol) of the inhaled thiophene was absorbed from the respiratory system. Within 72 h following exposure, a total of 488 mumol of thiophene equivalents (99% of that retained) was excreted, of which 360.4 mumol (73.9% of the total excreted radioactivity) was in expired air, 120.7 mumol (24.8%) was in urine, 3 mumol (0.6%) was in feces, and 3.7 mumol (0.8%) was in the cage wash. Excretion took place primarily within the first 8 h, during which 91% of the total radioactivity excreted was collected. The thiophene equivalents remaining in tissues at 72 h were estimated to total 5.1 mumol (1.0% of the retained radioactivity). Exhaled radioactivity was identified as thiophene. No 14CO2 was detected in the expired air. After 1 h following exposure, the elimination of thiophene equivalents from plasma was monophasic, with a half-time of 3.6 h. The elimination of thiophene equivalents from blood cells was biphasic, with half-times of 2.9 h and 9.1 d. The blood cells/plasma concentration ratios of thiophene equivalents ranged from 3 to 13, with the higher ratio observed at the 12-h time interval. At 72 h after exposure, blood cells contained the highest concentration of thiophene equivalents, approximately fourfold higher than that of the liver, which contained the second highest concentration. Kidney, heart, and lung contained similar but lower concentrations than liver, while brain, fat, and skeletal muscles contained the lowest concentrations. In summary, this study demonstrates that thiophene was absorbed from the respiratory system, and the majority of the absorbed thiophene was eliminated unchanged in the exhaled air, while a smaller fraction was metabolized and eliminated in urine. PMID- 8501767 TI - Teratogenic effects of noise and cadmium in mice: does noise have teratogenic potential? AB - The teratogenicity of combined exposure to noise and cadmium was studied in mice. ICR mice were exposed to a wide octave-band of noise at 100 dB(C) for 6 h on d 7 of pregnancy in one of two ways: continuous exposure or intermittent (15 min on/15 min off). Cadmium sulfate at 1 or 2 mg/kg was intraperitoneally injected on d 7 of pregnancy. Four groups were exposed to both cadmium and noise. On d 18 of pregnancy, fetuses were examined for external and skeletal malformations. Another experiment was performed with two other patterns of noise exposure: continuous exposure for 3 h, and intermittent exposure (5 min on/5 min off) for 6 h on d 7 of pregnancy. In the groups exposed to continuous noise for 6 h, total percentages of malformed fetuses were significantly higher than that in the control group, but there were no significant increases of total percentages of fetal malformations in the combined treatment groups in comparison with the groups given the same dose of cadmium alone. The percentages of skeletally malformed fetuses in groups exposed to 6 h of continuous noise were significantly higher than in groups that received saline or the same dose of cadmium. There were no significant differences in the total percentages of malformed fetuses between the control group and the groups exposed to a total of 3 h of noise, whether continuously or intermittently. Although combined treatment with cadmium and noise resulted in an increase of total percentages of malformed fetuses compared to the same dose of cadmium alone, the interactions between cadmium and noise showed no synergistic effect on teratogenicity. The magnitude of teratogenicity due to noise is much weaker than that of cadmium, and is therefore easily masked by that of cadmium in statistical tests of the significance of differences. PMID- 8501768 TI - Acute and delayed effects of diisopropyl fluorophosphate on body temperature, heart rate, and motor activity in the awake, unrestrained rat. AB - Acute exposure to diisopropyl fluorophosphate (DFP) causes irreversible inhibition of acetylcholinesterase activity, leading to various behavioral and autonomic sequelae including hypothermia, reduced motor activity, and other neurological dysfunctions. To characterize the acute response and recovery of autonomic and behavioral processes to DFP exposure, rats of the Long-Evans strain were implanted with radiotransmitters that allowed the monitoring of core temperature, heart rate, and motor activity in unrestrained animals 24 h/d. These parameters were monitored for 96 h following subcutaneous injection of DFP at a dose of 0, 0.1, or 1.0 mg/kg. Rats given 0 and 0.1 mg/kg DFP displayed an increase in core temperature and motor activity during the first 24 h postinjection. The 1.0 mg/kg group showed a typical hypothermic response for the first 24 h following DFP administration. Core temperature decreased a maximum of 1.9 degrees C by 5 h after DFP and then started to recover, reaching control levels by 17 h after DFP treatment. Motor activity was also depressed during the first 24-h period in the 1.0 mg/kg group. Heart rate was initially elevated above basal levels in all treatment groups for several hours after treatment, but the 1.0 mg/kg group showed a decrease in heart rate at the time when core temperature began its recovery from hypothermia. Core temperature was the only parameter significantly affected by DFP during the 24-96 h recovery phase. The 0.1 and 1.0 mg/kg groups showed a significant elevation in core temperature for the 3 d after DFP administration. The elevation in core temperature during the recovery from DFP treatment may represent an important facet of the acute cholinergic neurotoxicity of organophosphate compounds. PMID- 8501769 TI - Effects of exposure to sulfuric acid-aerosol on airway responsiveness in guinea pigs: concentration and time dependency. AB - We investigated the concentration and time dependency of the effects of exposure to sulfuric acid (H2SO4) aerosol on airway responsiveness. Two hundred and sixteen male Hartley guinea pigs were used. The animals were divided into 3 groups (n = 72/group), with 1 group being exposed to filtered air and the other 2 to 1.0 mg/m3 or 3.2 mg/m3 H2SO4 aerosol. In each group, the animals were divided into 4 subgroups (n = 18/subgroup), with exposure terms of 3 d (24 h/d), 7 d, 14 d, and 30 d. Specific airway resistance (SRaw) under room air (SRaw0) and airway responsiveness were determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Specific airway resistance values under room air (SRaw0) prior to and after exposure were compared. There was no significant change in SRaw0 after the exposure to filtered air, 1.0 mg/m3, or 3.2 mg/m3 H2SO4 aerosol. Our results also showed that exposure to filtered air or 1 mg/m3 H2SO4 aerosol did not cause any significant change in airway responsiveness to inhaled histamine aerosol, expressed as the effective concentration of histamine (EC200His) that produced a doubling of SRawNaCl (SRaw after exposure to aerosol of 0.9% NaCl saline). On the contrary, exposure to 3.2 mg/m3 H2SO4 aerosol induced transient airway hyporesponsiveness after a 3-d exposure [EC200His prior to and after exposure: 1.35 +/- 0.28 and 2.23 +/- 0.22 mM (p < .01), respectively] and then transient hyperresponsiveness after a 14-d exposure [EC200His prior to and after exposure: 1.65 +/- 0.21 and 0.95 +/- 0.23 mM (p < .01), respectively]. Overall, the present results revealed that (1) 1.0 mg/m3 or 3.2 mg/m3 H2SO4 aerosol had no significant effect on SRaw0 during a 30-d exposure period, (2) a high concentration (3.2 mg/m3) of H2SO4 aerosol affected airway responsiveness during the 30-d exposure, while a low concentration (1.0 mg/m3) of H2SO4 aerosol did not, and (3) the effect of exposure to 3.2 mg/m3 H2SO4 aerosol on airway responsiveness was transient and stimulatory or inhibitory, depending on the duration of exposure. PMID- 8501770 TI - Production of complement component C3 in vivo following 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure. AB - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to decrease serum complement C3 levels in female B6C3F1 mice but failed to alter C3 production when added in vitro to either hepatoma cells (both human and mouse hepatoma cells) or mouse primary hepatocytes (Lin and White, 1993a). It has also been demonstrated that mouse liver intracellular C3 levels were not affected following TCDD exposure in vivo, while serum C3 levels were suppressed (Lin and White, 1993b). Therefore, further studies were undertaken to investigate the mechanism by which TCDD modulates newly synthesized serum C3 in vivo. Mouse serum C3 was depleted by an intravenous injection of 50 anti-complement units (ACU)/kg cobra venom factor (CVF). This dose of CVF depleted serum C3 levels to 9% of control at 24 h after treatment. Subsequently, serum C3 levels returned to 19% and 75% of the control level on d 3 and d 5. The recovery of serum C3 was then monitored following an acute oral exposure to 20 micrograms/kg TCDD. In mice exposed to both TCDD and CVF, serum C3 levels reached 15% and 69% of control on d 3 and d 5 after treatment; these results were not significantly different from those of mice treated with CVF alone. Furthermore, when the radiolabeled amino acid [3H]leucine was injected intravenously into either vehicle- or TCDD-treated mice, the incorporation of this labeled precursor into both C3 and other secreted plasma proteins was not inhibited by TCDD. These results demonstrated that TCDD did not decrease newly synthesized C3 in vivo. These studies provide additional support for the concept that TCDD does not act directly on hepatocytes to suppress C3 production. The lower serum C3 levels observed in vivo following TCDD exposure is not the result of a decrease in C3 production by hepatocytes. PMID- 8501771 TI - Whole body exposures to a phosphoric acids aerosol: I. Spontaneous activity effects in wild rodent and avian species. AB - Two inhalation-chamber studies were conducted to assess acute (2-h out-of chamber) and subacute (< or = 6 d postexposure) spontaneous activity effects of whole-body phosphoric acids aerosol exposure(s) in black-tailed prairie dogs (Cynomys ludovicianus) and rock doves (Columba livia). The aerosol was generated using a red phosphorus/butyl rubber (RP/BR) mixture under development as a military obscurant. Each study involved (1) 3 RP/BR target concentration groups [0.0 (controls), 1.0, and 4.0 mg/L], (2) 24 prairie dogs or rock doves (8/group), with gender included as a factor, (3) a successive 3-phase paradigm (2 d preexposure; 4 and 2 d of about 80 min/d exposures to RP/BR for prairie dogs and rock doves, respectively; and 6 d postexposure), and (4) infrared detection of the rodents'/birds' home-cage movements. In-chamber atmospheres were uniform and acceptable for all exposures; median aerosol mass concentrations ranged from 0.76 to 0.89 mg/L and 3.46 to 3.74 mg/L for the 1.0 and 4.0 mg/L groups, respectively, with median phosphoric acid (H3PO4) readings of between 67.2 and 74.3%; median particles were < or = 0.85 microns. Mortality was negligible; no prairie dogs died, but 1 male rock dove died on d 3 postexposure to two 4.0 mg/L target concentrations of RP/BR aerosol. Group x session interactions were significant for the acute activity counts of both species. The acute mean ambulatory (e.g., walking) counts of prairie dogs and the acute mean ambulatory and horizontal (e.g., preening) counts of rock doves exposed to 4.0 mg/L RP/BR aerosol were relatively less than those of the other groups after the first 2 or 1 exposures, respectively. Nevertheless, acute session means for all groups approximated or exceeded the 23 h/d activity measured during the pre- and postexposure phases- data indicating that chamber confinement caused a temporary, sharp increase in activity for both species irrespective of RP/BR aerosol concentrations. No RP/BR concentration-related, subacute shifts in the activity of the rodents/birds were observed. PMID- 8501772 TI - Fungal infections of the genitourinary system. PMID- 8501774 TI - The challenge of kidney transplant nephrectomy. AB - During a 5-year-period 92 kidney transplant nephrectomies were performed and 87% of these kidneys were removed by a subcapsular technique. Surgical complications occurred in 4% of the cases. Renal allograft nephrectomy is a more complex and riskier operation than simple native nephrectomy. PMID- 8501773 TI - Absent ras gene mutations in human adrenal cortical neoplasms and pheochromocytomas. AB - A variety of human tumors have been studied for ras mutations to date. However, little is known about the prevalence and significance of ras gene activation in adrenal neoplasms. Recently, a study of 10 primary human pheochromocytomas found no evidence for ras mutations. To our knowledge no survey of ras mutations in adrenocortical neoplasms has been reported. Therefore, we analyzed deoxyribonucleic acid (DNA) from 17 archival tumors (8 adrenocortical carcinomas, 6 pheochromocytomas, 2 adrenal adenomas, 1 aldosteronoma, 2 fresh pheochromocytomas and 1 fresh benign adrenal gland) for activating mutations at the 12, 13 and 61 codons of N-ras, H-ras and K-ras. DNA was extracted from archival tissues using 3 different methods: a simplified boiling method, a proteinase-K-phenol chloroform extraction and a novel heat-stable protease Thermus rt41A technique. The boiling and heat-stable protease methods provided for more consistent polymerase chain reaction amplifications than the more laborious phenol chloroform method. This heat-stable protease Thermus rt41A method had not been reported previously for use in archival DNA extraction. Polymerase chain reaction amplified the ras gene regions of interest, and mutations were screened by mutation-specific oligonucleotide probe hybridization of Southern and slot blots. Polymerase chain reaction-generated mutation-specific positive and negative controls were used in the hybridization protocol. With these controlled conditions no definite mutations were detected at codons 12, 13 or 61 of N, H or K-ras. Ras activation via point mutations at these codons rarely, if ever, occurs in adrenal neoplasms. PMID- 8501776 TI - The stomach: a new and powerful oxalate absorption site in man. AB - New information is provided regarding the site and nature of intestinal oxalate absorption in man. Intestinal absorption of oxalate was assessed indirectly from the increase in renal oxalate excretion following gastric administration of 5 mmol. oxalate loads. Four different types of loads have been used: sodium oxalate, sodium oxalate plus calcium gluconate, rhubarb and spinach. Studies were performed in 6 adult patients on permanent gastric tube feeding for various reasons. Gastric emptying was blocked by an intrapyloric balloon for the duration of the experiments and the gastric oxalate load was evacuated before the balloon was deflated. Under these conditions calcium oxalate was absorbed to the same extent as soluble oxalate. With increasing gastric loading time there is a linear increase in the urinary oxalate excretion: 15 to 21% of the gastric oxalate load appeared in the urine after 2 hours of loading, 24 to 45% after 4 hours and as much as 62% after 6 hours. These absorption kinetics and our experiment suggest that the stomach is not only just another oxalate absorption site but seems to be the critical site for intestinal oxalate absorption in an intact gastrointestinal tract. This finding opens a new field for the discussion of etiology and pathogenesis of calcium oxalate stone formation. PMID- 8501775 TI - Iron deficiency anemia after successful renal transplantation. AB - In patients with chronic renal failure, renal transplantation improves anemia and the production of erythropoietin. In patients undergoing hemodialysis the administration of recombinant human erythropoietin improves anemia with a decrease in bodily iron stores. Therefore, one would expect a similar decrease after kidney transplantation. We followed the ferric parameters to determine the incidence of iron deficiency anemia in 24 consecutive renal transplant patients for an interval long enough to achieve steady state values of hemoglobin (5.1 +/- 0.8 months). Hematological parameters and serum levels of iron, ferritin and erythropoietin were measured. The patients were divided into 2 groups according to the decrease in serum ferritin: group 1--16 with a decrease in respect to basal values (114 +/- 56 ng./ml.) and group 2--those without modifications (720 +/- 320 ng./ml.). Except for the similar values, group 1 showed greater improvement in anemia (red blood cells 4.3 x 10(6) +/- 1.1 x 10(6) versus 3.7 x 10(6) +/- 1.5 x 10(6)/ml., p < 0.01) and hematocrit index (38.5 +/- 5.2 versus 33.0 +/- 5.1%, p < 0.05). Four patients had microcythemia (mean corpuscular volume 76.6 +/- 1.4 fluid) with lower hemoglobin values than the other patients in group 1 (10.77 +/- 0.42 versus 12.79 +/- 0.42 gm./dl., p < 0.05). Among the 16 patients in group 1, 7 of 8 whose basal serum ferritin was less than 150 ng./ml. achieved ferritin levels of less than 30 ng./ml. In conclusion, our data support that renal transplantation produces a rapid decrease in iron stores and in some cases induces iron deficiency anemia. This fact should be evaluated and treated properly. PMID- 8501777 TI - Effect of orange juice consumption on urinary stone risk factors. AB - The value of orange juice consumption in kidney stone prevention was examined in 8 healthy men and 3 men with documented hypocitraturic nephrolithiasis. They underwent 3 phases of a metabolic study, a placebo phase and 2 treatment phases in which they ingested either 1.2 l. orange juice (containing 60 mEq. potassium and 190 mEq. citrate per day) with meals or potassium citrate tablets (60 mEq. per day) with water and meals. Compared to potassium citrate, orange juice delivered an equivalent alkali load and caused a similar increase in urinary pH (6.48 versus 6.75 from 5.71) and urinary citrate (952 versus 944 from 571 mg. per day). Therefore, orange juice, like potassium citrate, decreased urinary undissociated uric acid levels and increased the inhibitor activity (formation product) of brushite (calcium phosphate). However, orange juice increased urinary oxalate and did not alter calcium excretion, whereas potassium citrate decreased urinary calcium without altering urinary oxalate. Thus, orange juice lacked the ability of potassium citrate to decrease urinary saturation of calcium oxalate. Overall, orange juice should be beneficial in the control of calcareous and uric acid nephrolithiasis. PMID- 8501779 TI - Low energy lithotripsy with the Lithostar: treatment results with 19,962 renal and ureteral calculi. AB - Between November 1988 and January 1992, 19,962 renal and ureteral calculi were treated in the United States using 18 different mobile and 2 fixed base Lithostar lithotriptors. Lithotripsy was performed on 11,516 renal and 8,446 ureteral calculi by 750 urologists using the same technique. The success rate (asymptomatic with stone fragments of 4 mm. or less) for renal stones was 87.9%, the stone-free rate was 68.9% and the retreatment rate was 16.5%. Auxiliary procedures were performed in 32.2% of the renal calculi. The success rate for ureteral calculi was 89.5%, the stone-free rate was 83.5% and the retreatment rate was 10.7%. Auxiliary procedures were performed in 25.5% of the ureteral calculi. The overall success rate was 88.4% stone-free rate 75.5%, retreatment rate 14.0% and auxiliary procedure rate 29.4%. Anesthesia personnel were used in 1.9% of the cases. Low energy extracorporeal shock wave lithotripsy was found to be safe and effective. PMID- 8501778 TI - Increased levels of calbindin-D in serum and urine from patients treated by extracorporeal shock wave lithotripsy. AB - Calbindin-D 28 kDa. is a vitamin D-dependent calcium binding protein that is found mainly in the distal renal tubules and central nervous tissue in humans. Calbindin-D was measured in the serum and urine before, and immediately, 2 hours or 24 hours after extracorporeal shock wave lithotripsy (ESWL*) in 83 consecutive patients. ESWL was performed with the Siemens Lithostar device in 61 patients and with the Dornier MPL9000 lithotriptor in 22. The serum 28 kDa. calbindin-D level was undetectable (less than 20 pg./ml.) in many samples, whereas urinary 28 kDa. calbindin-D could be detected in every sample. The serum 28 kDa. calbindin-D level was usually elevated after ESWL and the concentration in patients treated with the MPL9000 device was greater than in those treated with the Lithostar instrument. Urinary 28 kDa. calbindin-D levels were elevated significantly immediately and at 2 hours after ESWL, and they decreased to the baseline level within 24 hours after ESWL in the Lithostar group but remained consistently significantly elevated after ESWL in the MPL9000 group. This fact may be because the MPL9000 lithotriptor produces a stronger shock wave than does the Lithostar device during ESWL. These results suggest that 28 kDa. calbindin-D is released from damaged distal renal tubule cells into the serum and urine during ESWL and that 28 kDa. calbindin-D is a specific marker for renal damage by ESWL. To our knowledge this is the first clinical study using a sensitive enzyme immunoassay for human 28 kDa. calbindin-D to estimate renal damage during ESWL. PMID- 8501780 TI - Extracorporeal shock wave lithotripsy for distal ureteral stones. AB - A retrospective analysis of distal ureteral calculi treated by extracorporeal shock wave lithotripsy (ESWL*) as the primary mode of therapy was performed. Using the Dornier HM3 unit 312 patients underwent a total of 326 ESWL procedures. Several pretreatment procedures, including placement of ureteral catheters were used to help with stone localization. Early fragmentation and 3-month stone-free rates were analyzed. Of the patients 81% were stone-free at 3 months. We reviewed 27 failures, revealing a higher incidence of impacted stones and stones greater than 1 cm. Complications were few and minor. ESWL is a safe and effective treatment option for distal ureteral calculi. PMID- 8501781 TI - An innovative approach to management of lower third ureteral calculi. AB - A total of 130 patients with symptomatic lower third ureteral calculi underwent 136 treatments by 43 accredited urologists. These treatments were performed at a fixed lithotripsy site and 16 mobile sites using the Medstone lithotriptor from December 1990 through January 1992. The average stone size was 8.16 x 5.14 mm. A total of 126 patients underwent a single treatment and 4 underwent multiple treatment sessions. Of the 126 patients undergoing monotherapy 10 (8%) were lost to followup, while 101 of the remaining 116 evaluable patients (87%) were stone free with a single treatment. The 15 patients in this subgroup who were considered failures and the 4 patients who underwent multiple treatments had overall larger stone sizes. The preoperative stent placement rate was only 32%. The treatments were well tolerated by the patients. Our report confirms a high efficacy rate with the second generation bathless lithotriptor for management of lower third ureteral calculi. The importance of a stable and qualified technical team cannot be overemphasized. PMID- 8501782 TI - Laparoscopic stapled bladder closure: laboratory and clinical experience. AB - We report our experience with closure of the bladder during laparoscopic nephroureterectomy by using a gastrointestinal anastomosis type stapling device designed to deliver 6, 3 cm. rows of 3.5 mm. titanium staples via a 12 mm. trocar. We initially used this stapling device to secure a cuff of bladder in 8 female pigs undergoing laparoscopic nephroureterectomy. Followup in these animals was completed 2 to 6 months postoperatively. Then, 3 patients underwent laparoscopic ureterectomy using the laparoscopic stapler to transect and secure the ureter along with a cuff of bladder. In neither the laboratory nor the clinical situation were any complications encountered due to the transvesical staples (for example extravasation, stone formation, urinary tract infection or abscess formation). Our preliminary results indicate that titanium staples may be an effective method to provide rapid and secure closure of the bladder in patients undergoing either laparoscopic nephroureterectomy or laparoscopic ureterectomy. PMID- 8501783 TI - Modified ileocolonic bladder: 5 years of experience. AB - A total of 25 patients 17 to 78 years old (mean age 61 years) underwent bladder replacement with a modified ileocolonic bladder: 20 underwent construction of the neobladder following cystoprostatectomy for invasive bladder tumor, 4 after cystectomy for severe interstitial cystitis and 1 for undiversion. There were 21 men and 4 women. Followup ranged from 3 to 66 months. There were no perioperative deaths. The early complication (perioperative 3 months) and late complication rates were 18% and 16%, respectively. Complications included ureterocolonic anastomotic strictures in 4 ureters (3 were treated via endoscopic retrograde balloon dilation and 1 with endourological antegrade dilation), urethral strictures in 2 patients, treated by urethral dilation, pancreatitis 2 weeks postoperatively in 1 and mild hypercholoremia without concomitant acidosis in 2. One patient presented 3 years postoperatively with a left mid ureteral stone that was managed by ureteroscopic extraction. Three patients died of recurrent carcinoma (none with urethral recurrence). The daytime continence rate was 100% and the nighttime continence rate was 92%. The ureters in this modified ileocolonic bladder were placed in an anatomically correct position to resemble a trigone near the mouth of the neobladder with the left ureter uncrossed. This placement provided easy visualization and instrumentation of the upper urinary tract. No patient had vesicoureteral reflux. PMID- 8501784 TI - Behavioral therapy for the treatment of refractory interstitial cystitis. AB - The short-term results of behavioral therapy in 42 women with refractory symptoms of interstitial cystitis were retrospectively analyzed. All patients had persistent symptoms at least 2 years in duration despite undergoing a number of empiric therapies. Symptoms included urinary frequency and urgency of at least once every 2 hours during waking hours and persistent pain or discomfort in the suprapubic, perineal or pelvic area. Treatment consisted of diary keeping, timed voiding, controlled fluid intake and pelvic floor muscle training techniques. After a mean of 12 weeks of treatment the inter-voiding interval increased in all patients by a mean of 93 minutes (p < 0.01) and 98% experienced a decrease in the number of micturitions per day by a mean of 9 (p < 0.01). Using a global assessment scale 50% of the patients reported that the symptoms were markedly improved and 38% were improved. These data confirm the short-term efficacy of behavioral therapy in selected patients with symptoms of interstitial cystitis. PMID- 8501785 TI - Percutaneous nephrostomy for treatment of intractable hemorrhagic cystitis. AB - Six patients with severe hemorrhagic cystitis unresponsive to traditional localized therapy were treated with percutaneous nephrostomy for diversion of urine. Bladder hemorrhage ceased in 3 patients, decreased in 2 and was unchanged in 1. In 1 patient with profound thrombocytopenia perirenal hematoma developed as a result of the nephrostomy placement but this complication was self-limited and did not require surgery. Our experience with these 6 patients indicates that nephrostomy diversion is safe and effective in most cases of hemorrhagic cystitis refractory to traditional, nonoperative therapy. Percutaneous urine diversion may obviate the need for surgical urinary diversion in patients who have intractable hemorrhagic cystitis. PMID- 8501786 TI - Enhanced glutathione S-transferase activity and glutathione content in human bladder cancer. Followup study: influence of smoking. AB - Glutathione content and glutathione S-transferase activity have been studied in human bladder specimens obtained from controls and from patients with superficial transitional cell carcinoma (tumor samples and peri-tumor normal tissues from the same patient). After combining an earlier study from our laboratory with the additional material presented (9 healthy controls and 25 transitional cell carcinoma patients), it can be observed that glutathione S-transferase activity was significantly greater in tumor than in peri-tumor normal tissue (34 patients, p < 1 x 10(-7)) or in normal mucosa (17 controls, p < 1 x 10(-3)). Glutathione content was significantly greater in tumor than in peri-tumor normal tissue (p < 5 x 10(-3)) or in normal mucosa (p < 2 x 10(-2)), with this increase being evident only in smokers. When comparing normal mucosa and peri-tumor samples no significant differences were found either for glutathione S-transferase activity or for glutathione content. Results demonstrate the relationship between the glutathione S-transferase/glutathione system and development of transitional cell carcinoma, as well as its role in cellular resistance to chemotherapy. PMID- 8501787 TI - Natural history of urogenital trichomoniasis in men. AB - Although Trichomonas vaginalis is a common sexually transmitted pathogen, the significance and natural history of trichomoniasis remain undefined in the male patient. We conducted a longitudinal study to examine the relationship of T. vaginalis to nongonococcal urethritis in men and to increase our understanding of the natural history of this infection. As previously reported, T. vaginalis was isolated from 50 of 447 men attending a sexually transmitted disease clinic by culture of urethra, first-void urine or external genitalia. Semen cultures proved valuable for documentation in select cases, including 4 instances when concomitant cultures of the external genitalia, urethra and first-void urine sediment were all negative. Spontaneous resolution was documented in 36% of untreated men but 1 asymptomatic man had persistence of T. vaginalis throughout a 4-month period. Nongonococcal nonchlamydial urethritis was documented in 12 of 21 men (57%) at the visit before treatment or spontaneous resolution compared to only 2 (10%) after elimination of T. vaginalis (p < 0.001). These findings suggest that spontaneous resolution of trichomoniasis and prolonged asymptomatic carriage occur in men with trichomoniasis and that T. vaginalis is a treatable cause of urethritis among sexually active men. PMID- 8501788 TI - The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women. AB - The influence of age, parity, duration of previous oral contraceptive use, hysterectomy and menopause on the prevalence of urinary incontinence was evaluated by means of a postal questionnaire in women 46 to 86 years old who resided in the city of Goteborg, Sweden. A sample of 10,000 women from the 7 birth cohorts of 1900 to 1940 was obtained at random from the population register. The overall response rate was 74.6%. The prevalence of urinary incontinence increased (p < 0.001) in a linear fashion from 12.1% in the 1940 birth cohort to 24.6% in the 1900 birth cohort. The prevalence of urinary incontinence in nulliparous women was 7.7% in the 1930 birth cohort and 5.5% in the 1940 birth cohort. The corresponding figures for women who had experienced 1 delivery were 11.1% and 10.6%, compared to 14.0% and 16.4% among women who had had 3 or more deliveries. Urinary incontinence was more prevalent in women who had undergone hysterectomy (p < 0.05). The prevalence of urinary incontinence was unaffected by the duration of previous oral contraceptive use and there was no evidence to suggest that the prevalence of urinary incontinence increased at the time of the last menstrual period. PMID- 8501789 TI - Construction of the neophallus in female-to-male transsexuals: the Amsterdam experience. AB - Until April 1991, 31 phalloplasties were performed in 28 patients at our hospital. Operative techniques and results of the use of the superficial inferior epigastric pedicled skin flap, rectus abdominis myocutaneous pedicled flap and radial forearm free flap for phalloplasty are presented and discussed. Functionally and cosmetically, the microsurgical free flap phalloplasty techniques lead to the best results. In all cases of free flap phalloplasty in our series tactile sensitivity recurred in the neophallus. However, erogenous sensibility should not be expected. We regard use of the infraumbilical flap to be a technique with few indications and it should not be applied to obese patients. Use of the rectus abdominis myocutaneous pedicled flap is a reliable technique. Primary connection of the pars fixa and pars pendulans urethrae often leads to formation of fistulas at the level of the anastomosis. Genital reassignment surgery in female-to-male transsexuals can seldom be achieved in 1 stage and this should be made clear to the patient before any form of surgery is done. PMID- 8501790 TI - What is the best pregnancy rate that may be expected from vasectomy reversal? AB - Pregnancy rates after vasectomy reversal vary among different reporting surgeons. To study those patients who are most likely to achieve pregnancy after vasectomy reversal, and to eliminate the effect of variations in surgical technique and operative findings on surgical outcome, the pregnancy rate after vasectomy reversal was calculated in men who achieved completely and consistently normal postoperative semen analyses (sperm concentration 20 x 10(6)/ml. or more and sperm motility 50% or greater). Of 95 patients who met the study criteria 58 (61.1%) achieved pregnancy and 37 (30.9%) did not. Including an allowance for some patients who will achieve pregnancy beyond the study-followup, it is concluded that the maximum pregnancy probability for vasectomy reversal is approximately 67%. Failure to achieve pregnancy in approximately a third of the patients may be explained by partner infertility, epididymal dysfunction and sperm antibodies. Studies that report pregnancy chances in excess of two-thirds must have different patient demographics and/or different methods of statistical analysis. PMID- 8501791 TI - Evaluation of the acute scrotum by color-coded Doppler ultrasonography. AB - Color-coded Doppler ultrasonography is a combination of real-time sonography and duplex sonography for noninvasive imaging of arterial and venous blood vessels. In 40 patients with acute onset of scrotal pain this diagnostic procedure was correlated with the findings at surgical exploration: 11 had testicular torsion, 4 hydatid torsion, 13 spontaneous detorsion, 2 blunt scrotal trauma and 10 epididymitis. For testicular torsion color-coded Doppler ultrasonography had a sensitivity of 82% and a specificity of 100%, and for epididymitis the sensitivity was 70% and specificity was 88%. Color-coded ultrasonography readily demonstrates testicular perfusion. In cases of incomplete or early torsion some residual perfusion may be detected leading to false-negative results. Despite this fact, color-coded Doppler ultrasonography currently is the most valuable diagnostic modality in the evaluation of the acute scrotum. PMID- 8501792 TI - Is tumor volume an independent predictor of progression following radical prostatectomy? A multivariate analysis of 185 clinical stage B adenocarcinomas of the prostate with 5 years of followup. AB - Tumor volume has been shown to be proportionate to Gleason grade, capsular penetration, seminal vesicle invasion, lymph node metastases and capsular margins of resection. Because these variables are often interrelated, it is crucial to determine which of these parameters provides independent prediction of prognosis in prostate cancer. The current study analyzed 185 men who underwent radial retropubic prostatectomy for clinical stage B adenocarcinoma of the prostate. Patients with seminal vesicle invasion or lymph node metastases were excluded, since these findings are almost invariably associated with progression. All patients were followed for a minimum of 5 years after radical prostatectomy. Only 2 men received postoperative adjuvant therapy. At 5 years after radical prostatectomy 58 men (31%) experienced progression, defined by either an elevated postoperative serum prostate specific antigen level, local recurrence or distant metastases. Although by themselves capsular penetration, tumor volume and per cent of the prostate involved by tumor predicted progression, in a stepwise regression analysis they did not provide independent prognostic information. In this multivariate analysis Gleason score was the best predictor of progression (p < 0.0001); surgical margin was the only other variable that enhanced prediction, although it was less influential than grade (p = 0.018). This strong predictability provided by Gleason score was all the more impressive given the relatively few patients in our study with either low or high grade tumor. Although an accurate preoperative assessment of tumor volume remains desirable for the management of patients with prostate cancer, our study demonstrates that measurement of tumor volume in radical prostatectomy specimens need not be performed as part of the routine pathological analysis of radical prostatectomy specimens, since it does not provide additional information beyond that of Gleason score and the status of capsular margins. PMID- 8501793 TI - Magnetic resonance imaging for detection of prostate cancer metastatic to bone. AB - The diagnosis of prostate cancer metastatic to bone currently is made with plain x-rays, radionuclide bone scans, and acid and alkaline phosphatases. We used magnetic resonance imaging (MRI) in 18 patients with known prostate cancer to resolve conflicting evidence of metastases found on bone scans, plain films and serum enzyme determinations. Of 8 bone scans interpreted as positive MRI was read as negative for metastatic disease in 2. Of 5 negative bone scans 1 MRI study was interpreted as positive. All 5 equivocal bone scans demonstrated no osseous lesions on MRI. In addition, in 6 patients with evidence of bone metastases the serial MRI scans following hormonal therapy demonstrated radiographic and clinical improvement. We conclude that MRI is helpful in the diagnosis of metastatic prostate cancer when other radiographic examinations are enigmatic and that MRI can be used to determine the response to hormonal treatment. PMID- 8501794 TI - Mitomycin C in combination with orchiectomy for newly diagnosed metastatic prostate cancer: preliminary results on a randomized trial. AB - The preliminary results of a randomized trial comparing orchiectomy versus orchiectomy and mitomycin C in 119 newly diagnosed metastatic prostate cancer patients are presented. Of 109 evaluable patients 57 were treated with orchiectomy alone and 52 received adjuvant intravenous mitomycin C. Mean interval to progression was 13 months in the orchiectomy group versus 11 months in the mitomycin C group. Preliminary analysis did not demonstrate a favorable effect of the combination with this chemotherapeutic agent compared to orchiectomy alone (p = 0.3). PMID- 8501795 TI - Ribbon dressing for circumcision. PMID- 8501796 TI - Urological dysfunction in patients with diastematomyelia. AB - Little information exists concerning voiding dysfunction associated with diastematomyelia (splitting of the spinal cord). We present 27 patients 4 days to 62 years old (mean 13 years) who underwent neurosurgical intervention for treatment of this disorder. Of these patients 14 had urological evaluation, with 11 having undergone video urodynamics. Nine patients had minimal urological manifestations. No patient had a urodynamically proved hostile bladder nor evidence of upper urinary tract deterioration. In our experience, patients with a spinal cord fixation syndrome resulting from diastematomyelia not associated with a meningomyelocele appear to have a relatively benign course in terms of the urological manifestations. However, due to the lack of reports concerning the urological findings in this occult dysraphic state, we still suggest upper and lower urinary tract evaluation and followup. PMID- 8501797 TI - Bilateral obstructing ureteral uric acid stones in an infant with hereditary renal hypouricemia. AB - We report on a 15-month-old boy with renal hypouricemia who presented with acute renal failure, anuria and sepsis due to bilateral obstructing ureteral uric acid stones. He was treated successfully with extracorporeal shock wave lithotripsy. Metabolic survey of 10 relatives revealed a rare hereditary disorder in 4 siblings: isolated renal hypouricemia and hyperuricosuria. To our knowledge this is the youngest reported case of hereditary renal hypouricemia and 1 of the youngest patients to be treated with extracorporeal shock wave lithotripsy. PMID- 8501798 TI - Massive hemorrhage from the diverted colon as a complication of rectourethral fistula repair: case report and review. AB - A case of congenital rectourethral fistula with massive hemorrhage from the diverted colon during the postoperative period is reported. The entity of diversion colitis is highly under recognized. The pathology and management are briefly discussed. PMID- 8501799 TI - Urological findings in patients with neurosurgically treated tethered spinal cord. AB - We studied 42 consecutive patients with spina bifida to ascertain the urological relevance of the tethered spinal cord in this condition. We evaluated 35 patients before untethering and 21 with pathological findings after untethering. The main difference after untethering was an increase in bladder capacity in 10 of 17 patients. The general clinical condition improved in 13 patients, was stable in 5 and became worse in 3. PMID- 8501800 TI - Pathogenesis of megalourethra. AB - Idiopathic megalourethra in infants is an enlargement of the pendulous urethra with no evidence of distal obstruction. Two aborted fetuses at 14 and 19 weeks of gestational age exhibited megalourethra with definite complete distal obstruction. The urethras of these 2 fetuses were studied histologically confirming the presence of an uncanalized epithelial core in the glans obstructing the lumen of the patent urethra. Embryologically, this epithelial core is normal but early canalization achieves continuity with the lumen of the penile urethra. In these 2 fetuses canalization was arrested or delayed with complete obstruction of the urethra in the glans and dilatation of the pendulous urethra. In living children with this form of megalourethra the urethra of the glans is patent. Canalization of the epithelial core in the glans of the survivors may have been delayed rather than arrested and may be a cause of megalourethra. PMID- 8501801 TI - Results of renal transplantation in boys treated for posterior urethral valves. AB - The results of renal transplantation in boys treated for posterior urethral valves were evaluated and compared with a matched control group. Patient and graft survival was equal in both groups, although serum creatinine levels were slightly higher in the posterior urethral valves group. Postoperative complications, such as urinary tract infections, occurred more frequently in the posterior urethral valves group. Urodynamic evaluation was performed before transplantation in 11 of 20 patients. Adequate treatment of bladder dysfunction, such as poor compliance and/or hyperreflexia, is essential in diminishing the risks of secondary graft damage due to severe bladder dysfunction. PMID- 8501802 TI - Phallic construction in prepubertal and adolescent boys. AB - During the last 10 years we performed microsurgical phallic reconstruction in 7 prepubertal and 4 adolescent boys. Indications for surgery included post traumatic amputation, circumcision accident, developmental anomalies and micropenis. In addition, we performed phalloplasty on 5 other patients 18 to 24 years old. Total phallic reconstruction consisted of 1-stage microsurgical tissue transfers that included urethral reconstruction, coaptation of erogenous nerves, aesthetic refinement and, in some cases, scrotal reconstruction. All postpubertal patients recovered erogenous sensibility in the reconstructed phallus and the ability to masturbate. Surgical indications, techniques and results are discussed. PMID- 8501804 TI - Perinephric abscess due to a coagulase-negative Staphylococcus: case report and review of the literature. AB - Perinephric abscess is an uncommon urinary tract infection that usually is caused by Staphylococcus aureus as a single pathogen or gram-negative bacilli as part of a polymicrobial process. We describe a man who presented with a right perinephric abscess due to coagulase-negative Staphylococcus as the only pathogen. The patient had bilateral nephrolithiasis, and he was treated successfully with percutaneous drainage of the abscess and parenteral antibiotics. Coagulase negative staphylococci are increasingly reported to cause serious infections. This organism can no longer be routinely dismissed as a contaminant or colonizer. Repeated isolation of coagulase-negative Staphylococcus in the absence of other pathogens must be considered a high risk situation. PMID- 8501803 TI - Synchronous bilateral carcinoma of the adrenal gland: 2 case reports. AB - The existence of synchronous bilateral adrenal masses is an uncommon condition except in the relatively more frequent cases of pheochromocytoma or metastatic tumors. Two cases of synchronous nonfunctioning bilateral adrenal cortex carcinoma, removed during the same operation, are described. The patients currently are receiving hormonal supplementation, and were well 16 and 12 months postoperatively. PMID- 8501805 TI - Extracorporeal shock wave lithotripsy complicated with miliary tuberculosis. AB - We report a case of miliary tuberculosis following extracorporeal shock wave lithotripsy (ESWL*). The patient had right lower caliceal and left distal ureteral calculi on excretory urography. He was hospitalized 50 days after ESWL with fever, weight loss and night sweats. Liver function tests were abnormal and he had hypoxemia. A chest x-ray at hospitalization was normal but a miliary pattern developed 10 days later. Diagnosis was tuberculosis based on culture of sputum in a Lowenstein medium. Liver biopsy confirmed caseating epithelioid granulomas. Antituberculous treatment was successful. We conclude that renal tuberculosis associated with calcification must be ruled out before treatment with ESWL to avoid a possible hematogenous dissemination. PMID- 8501806 TI - Benign retroperitoneal fibrosis and renal cell carcinoma. AB - We report benign retroperitoneal fibrosis associated with renal cell carcinoma in a 56-year-old woman. Based on the preoperative evaluation and initial surgical exploration, the retroperitoneal mass was assumed to be metastatic renal cell carcinoma and chemotherapy rather than surgical resection was offered to the patient. A second opinion was sought and repeat exploration revealed a resectable cell carcinoma and retroperitoneal tissue that was pathologically benign idiopathic retroperitoneal fibrosis. This report emphasizes that a patient with an otherwise resectable primary tumor must undergo multiple, deep biopsies of retroperitoneal masses before making a presumptive diagnosis of malignant retroperitoneal fibrosis secondary to metastatic cancer. PMID- 8501807 TI - Postpartum ovarian vein thrombosis presenting as ureteral obstruction: a case report and review of the literature. AB - Postpartum ovarian vein thrombosis, well described in the obstetrical literature with an incidence approaching 1 in 2,000 pregnancies, can present as a life threatening complication. Although infrequent, thrombophlebitis of the ovarian vein may remain unrecognized and result in pulmonary embolism with dire outcome. Postpartum ovarian vein thrombosis can present initially as an acute ureteral obstruction, making it incumbent upon the urologist to recognize the entity with its associated radiological and clinical findings. A case report is presented to illustrate the disorder. PMID- 8501808 TI - Ogilvie's syndrome: a potential complication of vaginal surgery. AB - Ogilvie's syndrome is a well described disorder of the gastrointestinal tract and is characterized by marked dilatation of the distal colon without mechanical obstruction. There are numerous proposed etiologies for this syndrome, which include an association with certain medical conditions, medications and major abdominal surgery. The occurrence of Ogilvie's syndrome, however, is not widely reported following vaginal operations. We present 3 cases in which procedures on the bladder neck performed through the vagina resulted in the development of postoperative Ogilvie's syndrome. Early diagnosis and treatment of this syndrome are important to avoid significant morbidity and mortality. PMID- 8501809 TI - Gangrenous cystitis: case report and review of the literature. AB - A case of gangrenous cystitis in a 67-year-old woman is reported. Associated etiological factors include invasive recurrent carcinoma of the cervix, radiotherapy and atherosclerosis. Primary infection was not a feature. The patient was treated with antibiotics, bladder drainage and total cystectomy with complete recovery. The etiology and management of this unusual condition are discussed. PMID- 8501810 TI - Percutaneous access to a continent urinary reservoir for removal of intravesical calculi: a case report. AB - Stone formation within urinary reservoirs is a well recognized problem. Various endourological techniques have been used to treat these stones. We report a case in which reservoir calculi were removed via a percutaneous approach. PMID- 8501811 TI - Reconstruction of a near total male urethral defect with a microvascular free flap. AB - We describe a new technique for reconstruction of a traumatic near total male urethral defect. With this procedure a microvascular free flap transfer of the radial forearm skin is used to create a 23 cm. neourethra extending from the urogenital diaphragm to the glans of the penis. This single-stage transfer allows large traumatic wounds to heal, enables the patient to urinate while standing without strictures, and maintains urinary continence. PMID- 8501812 TI - Repeat male genital self-mutilation precipitated by urinary complications of prior repair. AB - Male genital self-mutilation is uncommon, with repeat mutilation even more rare. Our case is unique in that a urological complication of the first mutilating act (meatal stenosis) helped to precipitate the second incident. This case underscores the need not only for immediate urological and psychiatric care at the time of initial mutilation but also for close, combined followup care as well. In the majority of cases, when properly monitored, the men do not repeat the mutilating act. PMID- 8501813 TI - Priapism of the clitoris: a case report following trazodone use. AB - We report a case of painful priapism of the clitoris lasting 24 hours, which was believed to be pathophysiologically associated with the administration of trazodone hydrochloride. Drug-induced unusual erectile activity in the clitoris has been described previously. However, to our knowledge this is the first reported case of drug-induced priapism of the clitoris. Management involved discontinuation of the offending agents and administration of adrenergic agonists to induce clitoral smooth muscle contraction. Clitoral function, proposed to be the ability to engorge and enable extrusion of the glans clitoris, was not obviously adversely affected by the priapistic episode. PMID- 8501814 TI - Re: Radical surgery for advanced prostate cancer and for radiation failures. PMID- 8501816 TI - Morphological and physiological changes in the urinary tract associated with ureteral dilation and ureteropyeloscopy: an experimental study. AB - The gross and microscopic effects of four common modes of ureteral dilation and ureteroscopy were examined in 26 renoureteral units in 13 minipigs. Acutely, ureters subjected to mechanical (bougie, Teflon, or balloon) ureteral dilation and ureteropyeloscopy (UPS) demonstrated active mucosal bleeding with multiple sites of perforation, whereas ureters subjected to hydraulic dilation and UPS were significantly less traumatized. Two weeks after mechanical ureteral dilation and UPS, 3 of 6 ureters were obstructed radiographically, whereas all 7 hydraulically dilated ureters were unobstructed. By 6 weeks, all radiographic evidence of obstruction had resolved in the mechanically dilated group. While 5 of 6 mechanically dilated ureters showed extensive scarring with muscle loss 4 to 6 weeks after dilation, no scarring was seen in those ureters dilated hydraulically. Renal pelvic pressure (RPP) was measured continuously with a nephrostomy catheter in vivo during (bougie, Teflon, balloon and hydraulic) ureteral dilation and UPS. Renal pelvic pressure during rigid ureteroscopy approximated the resting pelvic pressure plus the irrigant height above the kidney or set pressure on a hydraulic pump, plus a "scope effect" which was characterized by a 20 to 25 mm. Hg increase in RPP produced by moving the endoscope in the ureter without flow. The effects on RPP of continuous bladder drainage with a uretheral catheter and renal pelvic decompression with an open ended ureteral catheter passed into the renal pelvis through the ureteroscope working channel were also examined. The maximum RPP was evaluated in vitro in a separate group of 16 freshly harvested pig kidneys of similar weight examined immediately after sacrifice and was found to be 439 mm. Hg. We also studied the immediate and long-term effects of low (< 120 cm. H2O or 90 mm. Hg) versus high (> 200 cm. H2O or 150 mm. Hg) RPP on renal histology. Acutely, high pressure caused diffuse denudation and flattening of the caliceal urothelium, submucosal edema and congestion not seen in calyces subjected to low irrigant pressure. Four to six weeks later, there was a higher incidence of columnar metaplasia, subepithelial nests and pericalyceal vasculitis in calyces subjected to high pressure as compared with those subjected to low irrigant pressure. Acutely, renal tubules subjected to high irrigant pressure demonstrated marked vacuolization and degeneration, whereas tubules subjected to low pressure appeared normal. At 4 to 6 weeks, focal scarring was seen in 5 of 7 kidneys subjected to high irrigant pressure, whereas no scarring was noted in all 6 kidneys subjected to low irrigant pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501815 TI - Combined cavernous compression device and arteriovenous-cavernous fistula: a chronic canine model. AB - In 5 dogs studied over a 3-month period, we evaluated the chronic effects of the combination of deep dorsal vein arterialization with implantation of an inflatable venous compression device. The device was placed around the proximal corpora cavernosa, sparing the left dorsal artery. A left-to-right, end-to-side dorsal artery-dorsal vein fistula was fashioned, and the right dorsal vein was anastomosed to the corpus cavernosum as an end-to-side venocorporeal window. From postoperative day 15, the device was activated twice a day for 3 months. Intracavernous pressure (bilateral) and left dorsal artery blood flow were monitored, and the patency of the anastomoses was evaluated by vascular clamping, arteriography, cavernosography and microscopic dissection. The device was well tolerated, requiring no anesthesia during activation. (A sixth dog developed glanular hyperemia and priapism and was excluded from evaluation). With cuff inflation, the intracavernous pressure was significantly higher on the experimental side (range, 20 to 106 cm. H2O higher; p = 0.028), and arteriography demonstrated contrast flowing in the fistula and window in 3 of 4 dogs in which it was done. Both clamping and microscopic dissection of the specimen showed patency of the anastomoses in all 5 dogs. Histologic examination revealed maintenance of normal cavernous tissue histology. PMID- 8501817 TI - Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice. AB - Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 micrograms./pup/day for days 1 to 3) or 17 beta-estradiol (200 micrograms./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periurethral region of the prostate at the age of 1 year. The dysplastic lesions ranged from mild to severe and, in addition to emergence of nuclear anaplasia, the architectural pattern of the glands was disturbed. Prenatal estrogenization (100 micrograms./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia and occasional dysplasia in the ventral lobe of the prostate, but not in the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and extent of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined estrogen and androgen treatment of neonatally estrogenized mice for 3 months (between 9 and 12 months of age) augmented nuclear dysplasia, but no invasive growth was seen in this group, either. Mild epithelial dysplasia was found in the dorsolateral lobes and coagulating glands of similarly treated control animals. A relation between the activation of certain proto-oncogenes and the development of several cancers has been shown in humans and experimental animals. In the present study, Northern blot analysis of total RNAs showed that the levels of c-myc mRNA were increased in the ventral and dorsolateral lobes, coagulating glands and prostatic urethra of neoDES mice at the age of 9 months. However, it remains to be determined whether the increase in c-myc expression is involved in the development of hyperplastic and dysplastic changes in the prostate of neoDES mice. PMID- 8501818 TI - Sacral root stimulation for controlled micturition: prevention of detrusor external sphincter dyssynergia by intraoperative identification and selective section of sacral nerve branches. AB - Electrical stimulation of the S2 nerve root can be used to produce detrusor contraction and voiding in patients with spinal cord injury, but concurrent stimulation of the external urethral sphincter causes detrusor-sphincter dyssynergia. This has been managed with a second surgical procedure, peripheral transection of the pudendal nerve. In this study, performed in dogs after spinal cord transection, laminectomy and ventral foraminotomy permitted tracing of the S2 root into the pelvis, where its branches were identified by electrical stimulation and urodynamic recording. The pudendal (somatic) branch was sectioned; the autonomic branch innervating the detrusor was preserved. Electrical stimulation of the proximal S2 root then produced detrusor contraction without contraction of the external urethral sphincter. This approach, which requires a single operation and spares pudendal nerve functions mediated by nerve roots other than S2, may enable a neurostimulator to provide effective voiding, without detrusor-external sphincter dyssynergia, in man. PMID- 8501819 TI - Hyperbaric oxygen treatment for experimental cyclophosphamide-induced hemorrhagic cystitis. AB - Acrolein is a toxic metabolite of cyclophosphamide that causes hemorrhagic cystitis in 2 to 40% of treated patients. Hyperbaric oxygen (HBO) is used to treat poorly healing wounds in conditions such as Fournier's gangrene and radiation-induced cystitis. The present study was designed to evaluate the effects of HBO on acute acrolein-induced hemorrhagic cystitis in a rat model. Rats were divided into 4 groups. Group I served as a control and received only HBO prior to sacrifice. Group II received acrolein only, while groups III and IV received acrolein as well as HBO therapy. Hyperbaric oxygen (100% oxygen, 2.8 atmospheres, 90 minutes) was delivered twice a day for 4 days, with group III receiving a fifth HBO treatment just before acrolein and group IV receiving the fifth HBO treatment just after acrolein. After therapy, the amount of urothelial injury was determined morphometrically. Group II untreated rat bladders had only 33% of the urothelium intact after acrolein injury, whereas groups III and IV rat bladders had 93% (p < 0.01) and 55% (p < 0.01) intact urothelium, respectively, after treatment with HBO. The timing of the HBO treatment appeared to be a critical factor, with less injury occurring if the fifth HBO treatment immediately preceded acrolein. These results suggest that HBO may be useful as prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis. PMID- 8501820 TI - Inhibition of prostate cancer growth by estramustine and etoposide: evidence for interaction at the nuclear matrix. AB - Metastatic prostate cancer which is refractory to hormone therapy remains an incurable disease for which there is no effective therapy. We have begun to investigate the nuclear matrix, the RNA-protein network of the nucleus that plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. It was postulated that estramustine phosphate (EMP), an estradiol nitrogen mustard conjugate that binds to the nuclear matrix, might enhance the cytotoxicity of etoposide (VP-16), a topoisomerase II inhibitor that acts at the level of the nuclear matrix. In a nascent DNA synthesis assay, EMP and etoposide interact to selectively inhibit new DNA synthesis on the nuclear matrix. In vitro, EMP and etoposide appeared to act synergistically to inhibit the growth of the metastatic Dunning rat prostate adenocarcinoma cell line Mat-LyLu as well as the metastatic human prostate adenocarcinoma cell line PC-3. In vivo, EMP and etoposide inhibited prostate adenocarcinoma growth in the Dunning Copenhagen rat model. These data have formed the basis of a Phase I/II clinical trial to examine the effect of EMP and etoposide in patients with stage D hormone-refractory prostate cancer. PMID- 8501821 TI - A recombinant form of Pseudomonas exotoxin A containing transforming growth factor alpha near its carboxyl terminus for the treatment of bladder cancer. AB - The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor alpha (TGF alpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/TGF alpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGF alpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/TGF alpha KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGF alpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers. PMID- 8501822 TI - Laparoscopic partial nephrectomy in the pig model. AB - In an effort to further evaluate the potential application of laparoscopy to urologic surgery, we explored the feasibility of using this minimally invasive approach for performing a partial nephrectomy. Nine female pigs underwent laparoscopic partial nephrectomy (LPN) utilizing a plastic cable tie (15 mm. x 4 mm. x 1 mm.) to achieve renal ischemia and an Argon Beam Coagulator probe (ABC) (Birtcher Medical Systems) to fulgurate the transected surface. Six weeks after LPN, 6 pigs underwent creatinine clearance, renin level, arteriography, BP samples and were then killed. The renal remnants were weighed and sectioned for histological studies. These studies revealed excellent function of the renal remnant, no AV fistula, and no evidence of renovascular hypertension. LPN is a feasible, repeatable procedure in the pig. Control of the renal hilum, transient parenchymal compression with a plastic cable, and use of the argon beam coagulator are key elements in performing this procedure. PMID- 8501823 TI - A piece of my mind. In the footsteps. PMID- 8501824 TI - Transplantation pioneer predicts successful xenotransplantation soon. PMID- 8501825 TI - Despite tensions of monitoring world trouble spot, aircraft carrier becomes first to ban tobacco. PMID- 8501826 TI - Foundations join to help end health care barriers. PMID- 8501827 TI - From the Food and Drug Administration. PMID- 8501828 TI - From the Centers for Disease Control and Prevention. Mandatory bicycle helmet use -Victoria, Australia. PMID- 8501829 TI - From the Centers for Disease Control and Prevention. Use of smokeless tobacco among adults--United States, 1991. PMID- 8501830 TI - From the Centers for Disease Control and Prevention. School-based tobacco-use prevention--People's Republic of China, May 1989-January 1990. PMID- 8501831 TI - Diagnostic and therapeutic technology assessment. Use of Teflon preparations for urinary incontinence and vesicoureteral reflux. PMID- 8501832 TI - Blood pressure and serum creatinine. PMID- 8501833 TI - Blood pressure and serum creatinine. PMID- 8501834 TI - Gauging the accuracy of laboratory testing from Medicare data. PMID- 8501835 TI - Gauging the accuracy of laboratory testing from Medicare data. PMID- 8501836 TI - Gauging the accuracy of laboratory testing from Medicare data. PMID- 8501837 TI - Privacy beliefs and the violent family. PMID- 8501838 TI - House staff work hours, supervision, and quality of care. PMID- 8501839 TI - House staff work hours, supervision, and quality of care. PMID- 8501840 TI - HIV infection as leading cause of death among young adults in US cities and states. AB - OBJECTIVE: To describe the extent to which human immunodeficiency virus (HIV) infection has become the leading cause of death among young adults (25 to 44 years of age) in US states and cities of at least 100,000 population. DESIGN: Analysis of underlying causes of death using national vital statistics for 1990 by state and city. Deaths caused by HIV were defined as those with underlying cause assigned a code number of 042, 043, or 044, as established by the National Center for Health Statistics. RESULTS: Infection with HIV was the leading cause of death among young men in five states, causing 29% of their deaths in New York, 28% in New Jersey, 24% in California and Florida, and 16% in Massachusetts. Among young women, HIV was not the leading cause of death in any state. Among young men, HIV infection was the leading cause of death in 64 cities, with the proportion of deaths due to HIV ranging from 16% in Bridgeport, Conn, to 61% in San Francisco, Calif. Among young women, HIV infection was the leading cause of death in nine cities, with the proportion of deaths due to HIV ranging from 15% in Baltimore, Md, to 43% in Newark, NJ. CONCLUSION: In many US communities, HIV infection is the leading cause of death among young men and women, causing a large proportion of deaths in this age group. PMID- 8501841 TI - The completeness of AIDS case reporting in New York City. AB - OBJECTIVE--To assess the completeness of acquired immunodeficiency syndrome (AIDS) case reporting in New York City (NYC), and to determine whether the completeness of reporting differs in various populations. DESIGN--Retrospective record review of hospital laboratory logs, death certificates, hospital discharge records, and patient registries at private physicians' offices and hospital outpatient clinics. SETTING--Public and private hospitals, and private physicians' offices in NYC. PATIENTS--Adults and adolescents with AIDS or with illnesses suggestive of AIDS were identified using both population-based and nonrandom sampling techniques. These persons were matched with the NYC AIDS case registry, and the medical records of nonmatching persons were reviewed to determine whether they met the 1987 Centers for Disease Control and Prevention surveillance case definition for AIDS. MAIN OUTCOME MEASURES--The completeness of reporting was calculated for the five individual projects and for the aggregate database by gender, race/ethnicity, risk, borough of residence, age, first AIDS diagnosis, and year of diagnosis. RESULTS--Of 7015 persons with AIDS identified in the five projects, 5912 (84%) had been previously reported (range, 77% to 89%). The completeness of reporting ranged from 81% to 87% in all major gender, race/ethnicity, risk, borough of residence, and age subgroups. In a multivariate analysis, the odds of being unreported were significantly higher among outpatients in hospital clinics, out-of-state residents, persons with diagnoses other than Pneumocystis carinii pneumonia, and persons recently diagnosed with AIDS. CONCLUSIONS--This study indicates that the NYC AIDS surveillance system functioned effectively during the first decade of the AIDS epidemic. Completeness of-reporting studies are an integral part of AIDS surveillance, providing data that are critical for assessing the validity of the AIDS surveillance database. PMID- 8501842 TI - Declining serum total cholesterol levels among US adults. The National Health and Nutrition Examination Surveys. AB - OBJECTIVE: To examine the secular trend in serum total cholesterol levels of the US adult population. DESIGN: Nationally representative cross-sectional surveys with both an in person interview and a medical examination that included the measurement of blood lipid levels. SETTING/PARTICIPANTS: Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 through 1962, 1971 through 1974, 1976 through 1980, and 1988 through 1991. RESULTS: Mean serum total cholesterol levels in US adults aged 20 through 74 years have consistently declined over the time period 1960 through 1991. More than half of the decline occurred during the time period 1976 through 1991. This decline occurred across the entire distribution of serum cholesterol levels and in all age-sex groups. High-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels have not changed, suggesting that the decline in total cholesterol levels is due to a decline in low-density lipoprotein cholesterol levels. CONCLUSIONS: These results document a continuing and substantial decline in serum cholesterol levels among US adults. They suggest that public health programs, designed to reduce cholesterol levels, are proving successful. The observed downward trend in serum cholesterol levels has coincided with a continuing decline in coronary heart disease mortality. These observations suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol level of US adults to no more than 200 mg/dL (5.17 mmol/L) is attainable. PMID- 8501843 TI - Prevalence of high blood cholesterol among US adults. An update based on guidelines from the second report of the National Cholesterol Education Program Adult Treatment Panel. AB - OBJECTIVE: To estimate the current levels and trends in the proportion of US adults with high blood cholesterol based on guidelines from the second report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP II). DESIGN: Nationally representative cross-sectional surveys. SETTING/PARTICIPANTS: Data for 7775 participants 20 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III) (data collected from 1988 through 1991) and for 9797 participants 20 through 74 years of age from NHANES II (data collected from 1976 through 1980) were used. RESULTS: From the data collection period in NHANES II (1976 through 1980) to the period in NHANES III (1988 through 1991), the proportion of adults with high blood cholesterol levels (> or = 240 mg/dL [6.21 mmol bd) fell from 26% to 20%, while the proportion with desirable levels (< 200 mg/dL [5.17 mmol/L]) rose from 44% to 49%. Currently, using the ATP II guidelines and NHANES III data, 40% of all adults 20 years of age and older would require fasting lipoprotein analysis; and 29% of all adults would be candidates for dietary therapy (as compared with 36%, using NHANES II data). Based on 1990 population data, it is estimated that approximately 52 million Americans 20 years of age and older would be candidates for dietary therapy. Assuming that dietary intervention would reduce low-density lipoprotein (LDL) cholesterol levels by 10%, as many as 7% of all adult Americans (approximately 12.7 million) might be candidates for cholesterol-lowering drugs. This estimate reflects approximately 4 million adults with established coronary heart disease, of whom half are aged 65 years and older, and up to 8.7 million adults without established coronary heart disease, of whom up to 3.1 million are aged 65 years and older. CONCLUSIONS: Substantial progress has been made in reducing the prevalence of high blood cholesterol; yet a large proportion of all adults, approximately 29%, require dietary intervention for high blood cholesterol. PMID- 8501844 TI - Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) PMID- 8501845 TI - Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. AB - BACKGROUND: Red blood cell transfusion is commonly used to augment systemic oxygen delivery to supranormal levels in patients with sepsis. However, clinical studies have not consistently demonstrated that this therapeutic maneuver is accompanied by an increase in oxygen utilization at either the whole-body level or within individual organs. STUDY OBJECTIVES: To determine the effect of red blood cell transfusion on gastrointestinal and whole-body oxygen uptake. DESIGN: Prospective, controlled, interventional study. SETTING: Multidisciplinary intensive care unit of a tertiary care teaching hospital. PATIENTS: Twenty-three critically ill patients with sepsis undergoing mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method. Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability. Measurements were made prior to transfusion of 3 U of packed red blood cells. These were then repeated immediately following transfusion, as well as 3 and 6 hours later. There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours posttransfusion (including those patients with an elevated arterial lactate concentration). However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients. More importantly, we found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r = -.71; P < .001). In those patients receiving blood that had been stored for more than 15 days, the gastric intramucosal pH consistently decreased following the red blood cell transfusion. CONCLUSION: We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. We postulate that the poorly deformable transfused red blood cells cause micro circulatory occlusion in some organs, which may lead to tissue ischemia in some organs. PMID- 8501846 TI - Technology follies. The uncritical acceptance of medical innovation. PMID- 8501847 TI - Rising HIV-related mortality in young Americans. PMID- 8501849 TI - [Studies on urinary apolipoprotein H in diabetics]. AB - In order to elucidate the diagnostic significance of urinary apolipoprotein H (apo H), known as beta 2-glycoprotein I, urinary apo H levels were measured by a non-competitive enzyme immunoassay in diabetics without hypertension and Albustix positive proteinuria. The relationships between urinary apo H levels and urinary albumin (Alb) levels as well as clinical profiles in diabetics were investigated. The mean urinary apo H level in 45 diabetics was 264.2 +/- 189.5 micrograms/g.cr, and significantly higher than that in 41 healthy subjects (120.6 +/- 84.8 micrograms/g.cr, p < 0.01). Diabetics were classified into three groups based on urinary Alb levels; 17 group I patients with normoalbuminuria (U-Alb < 15mg/g.cr), 12 group II patients, whose urinary Alb levels were in between normo- and microalbuminuria (15 < or = U-Alb < 30mg/g.cr) and 16 group III patients with microalbuminuria (30 < U-Alb < or = 300mg/g.cr). The mean urinary apo H level in group I patients, who were regarded as without nephropathy, was 199.2 +/- 109.0 micrograms/g.cr, significantly higher than that in normal subjects (p < 0.01). The mean urinary apo H levels in group II and III were 271.4 +/- 177.1 and 327.8 +/- 246.1 micrograms/g.cr, respectively. These values were also higher than in normal subjects (both of p < 0.01). Urinary apo H levels correlated positively with urinary levels of glycosaminoglycan (r = 0.382, n = 45, p < 0.01), which was regarded as an indicator of the anion loss from glomerular basement membrane to urine, and with urinary N-acetyl-beta-D-glucosaminidase activities (r = 0.378, n = 37, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501848 TI - [Clinical significance of urinary methylguanidine in non-dialyzed patients with chronic renal failure--prediction of progression rate of renal dysfunction]. AB - To clarify a clinical significance of urinary methylguanidine (U-MG, micrograms/dl) in non-dialyzed patients with chronic renal failure, we measured U MG, urinary creatinine (U-Cr, mg/dl) and serum creatinine (S-Cr, mg/dl), concurrently and continually in 36 out-patients whose S-Cr was over 4.0 mg/dl. Fresh urine sample was obtained and U-MG was measured by an enzymic method. S-Cr concentrations (mean +/- SD) at the initiation of dialysis therapy were comparable in non-diabetics and in diabetics, being 13.4 +/- 4.54mg/dl and 8.23 +/- 1.96mg/dl, respectively, with statistical significance (p < 0.01). U-MG/Cr (micrograms/mg. Cr) values were also different between them, being 9.28 +/- 4.97 in non-diabetics and 5.19 +/- 1.29 in diabetics, but with lesser statistical significance (p < 0.05) than S-Cr. U-MG/Cr correlated well with the terms till the initiation of dialysis therapy (r = 0.7189, p < 0.001), more significantly than S-Cr (r = 0.5506, p < 0.001) in parabolic regression analysis. U-MG/Cr were greatly varied among the 7 patients, although whose S-Cr was nearly the same level (6.0-6.9mg/dl). Most importantly, the tendency was found in these patients that the higher U-MG/Cr, the earlier the renal replacement therapy instituted. These results suggests that U-MG/Cr can be reliable parameter to predict the progression rate of renal failure and to help to know when renal replacement therapy should be instituted. PMID- 8501850 TI - [The effects of acute administration of cadmium chloride on renal hemodynamics in rats]. AB - The decreases of glomerular filtration rate (GFR) and renal blood flow (RBF) after acute administration of cadmium have been reported. The recent studies about renal failure induced by heavy metals revealed that the decrease of glomerular ultrafiltration coefficient is an important contributing factor in the onset of acute renal failure and that the changes of renal hemodynamics are less prominent factors. To clarify whether the changes of renal hemodynamics contribute to the decrease of GFR caused by cadmium, we evaluated the changes of renal hemodynamics and inulin clearance after acute intravenous infusion of cadmium chloride in rats. Cadmium chloride was continuously infused at the rate of 3.0 mumol/kg/min into SD rats. Mean arterial pressure was significantly increased immediately after the infusion of cadmium and unchanged during the experiment. 20 minutes after the infusion of cadmium, inulin clearance was decreased by 70% of the control value but RBF and renal vascular resistance (RVR) were unchanged. Filtration fraction was significantly decreased. 30 minutes after the infusion of cadmium, inulin clearance was further decreased by 51% of the control value. At the period, significant decrease of RBF (72% of control value) and increase of RVR (156% of control value) were observed. Urinary excretion of sodium and the ratio of urinary sodium to urinary inulin excretion were unchanged until 20 minute and were significantly decreased 30 minutes after the infusion of cadmium. Urinary volume was not changed throughout the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501851 TI - [A clinical study of persistent hypotension in patients on chronic hemodialysis]. AB - In order to clarify the pathogenesis of hypotension seen in the patients on chronic hemodialysis, we studied the vascular reactivity to exogenous vasoactive substances and the change of plasma ANP level during hemodialysis treatment. The vascular responsiveness to intravenously infused norepinephrine was decreased in hemodialysis patients, particularly in hypotensive group, compared with healthy controls (< 0.05). The blood pressure response to angiotensin II was also diminished significantly in hypotensive patients, compared with normotensive patients (p < 0.05). The plasma ANP concentration before and after each hemodialysis treatment was not different statistically between hypotensive and normotensive patients. Furthermore, the change of plasma ANP concentration was not correlated with the blood pressure change during each hemodialysis procedure. These findings suggest that the decrease of vascular responsiveness may be a factor for causing persistent hypotension in patients on chronic hemodialysis, and that the plasma ANP level is not responsible for the pathogenesis of hypotension. PMID- 8501852 TI - [Circadian blood pressure pattern in the patients with chronic glomerulonephritis]. AB - Circadian blood pressure pattern in the patients with chronic glomerulonephritis was studied by ambulatory 24-hour blood pressure monitoring (ABPM). Subjects were 32 patients and were divided into three groups with various renal function; Ccr of 10 patients were normal (Ccr > or = 70 ml/min), 10 patients 30 < or = Ccr < 70 ml/min and the Ccr were below 30 ml/min in the other 12 patients. Blood pressure levels were significantly higher in reduced Ccr groups as compared with normal Ccr cases. The blood pressure gradient between day-time (7:00-19:00) and sleeping time (1:00-5:00) significantly decreased in the patients with renal impairment as compared with normal Ccr cases. And it positively correlated with Ccr (r = 0.51, p < 0.01). These results indicate that the patients with reduced renal function in chronic glomerulonephritis show abnormal circadian blood pressure pattern and nocturnal hypertension, which may require novel modification of antihypertensive treatment. PMID- 8501853 TI - [Lipid metabolism in daunomycin-induced nephrotic rats (Part 6)]. AB - Lipid metabolism in tissues and HDL were examined in daunomycin-induced nephrotic rats. 1) Daunomycin-induced nephrotic rats showed the decreased phospholipids, the increased cholesterol content in heart. Phospholipids, triglycerides and cholesterol content in brain, lung and spleen were similar in daunomycin-induced nephrotic rats and control rats. 2) Triglycerides content in hepatocytes was decreased in daunomycin-induced nephrotic rats. But, cholesterol esters content in hepatocytes was higher in daunomycin-induced nephrotic rats than control rats. 3) LCAT activity in serum was increased in daunomycin-induced nephrotic rats. 4) Apolipoproteins composition of HDL in daunomycin-induced nephrotic rats showed the increased apoA-I and the decreased apo E. These results show that the increased cholesterol esters in liver tissue are due to hepatocytes in daunomycin induced nephrotic rats. The increased HDL cholesterol content may contribute to the increase of LCAT activity in daunomycin-induced nephrotic rats. The increase of LCAT activity in serum results in the increased apo A-I content in daunomycin induced nephrotic rats. No direct evidence about the incorporation of HDL into liver is obtained from the present experiments and further study will be necessary to clarify this evidence. PMID- 8501854 TI - [Octreotide suppresses the kidney weight and glomerular hypertrophy in diabetic rats]. AB - It was previously demonstrated that initial kidney hypertrophy has been seen in diabetic animals and somatostatin infusion suppresses GFR and serum insulin like growth factor (IGF-1) in diabetic patients. I studied the effects of somatostatin analogue (octreotide) on glomerular hypertrophy in diabetic rats. The animals were randomized into six groups: two groups of streptozocin (STZ) induced diabetic, insulin-treated diabetic and non-diabetic rat groups. One of these three groups were treated with two daily subcutaneous injections of octreotide (10 micrograms x 2) for a period of five weeks. In diabetic rats, body weight, blood sugar, glucose excretion, serum insulin, urinary volume, urinary protein, serum creatinine or creatinine clearance did not differ in diabetic rats with vs. without octreotide injection, but kidney weight (2.97 +/- 0.12 vs. 3.28 +/- 0.08 mg, P < 0.05; mean +/- SEM) and estimated glomerular volume (9.13 +/- 0.22 vs. 12.77 +/- 0.34 x 10(5) microns 3, P < 0.001) were all reduced in diabetic rats with octreotide when compared with untreated diabetic rats. In non-diabetic rats, octreotide reduced body weight (340.3 +/- 6.5 vs. 367.1 +/- 3.8g, P < 0.01) and kidney weight (2.29 +/- 0.08 vs. 2.51 +/- 0.04 g, P < 0.05) when compared with non-diabetic rats without octreotide. Urinary protein excretion (8.57 +/- 1.39 vs. 14.29 +/- 1.53 mg/day, P < 0.05), serum 1GF-1 concentration (956.3 +/- 180.7 vs. 1546.1 +/- 88.1 mg/day, P < 0.05) and estimated glomerular volume (7.69 +/- 0.16 vs. 9.72 +/- 0.15 x 10(5) microns 3, P < 0.001) significantly differed in insulin treated diabetic rats with vs. without octreotide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501855 TI - [Glycerol-loading test in experimental acute renal failure using 31P magnetic resonance spectroscopy of the kidney]. AB - We observed that administration of exogenous glycerol reduces beta-ATP level and increases glycerophosphate level using magnetic resonance spectroscopy (MRS) of the kidney. A new "glycerol-loading test" for use with MRS in rats was developed. Sprague-Dawley rats were anesthetized and the left kidney was exposed and placed on surface coil. 31P-MRS (109.25MHz) of the kidney was performed using 10 microseconds, 90' pulse width and 2.308 sec repetition time with an accumulation of 200 times. MRS was performed 24 hours after induction of acute renal failure in each model of acute renal failure. Glycerol-loading test was performed by the intravenous infusion of 10% glycerol through jugular vein over a 60 min period. MRS was recorded every 10 min during glycerol infusion and for 60 min after cessation of infusion. In normal rats, beta-ATP level in the kidney was decreased to 52.0% of the pre-loading value at 55 min glycerol infusion and recovered to 66.7% 55 min after glycerol infusion was stopped. In the cisplatinum model, the reduction of beta-ATP and the increase of glycerophosphate levels following glycerol-loading was similar to that in normal rats; however, the recovery of beta-ATP level after infusion was stopped was weaker. Rats treated with glycerol and HgCl2 showed rather severe acute renal failure, but the beta-ATP level at 55 min glycerol infusion was 87.3% and 92.4%, respectively, showing difference from that in normal rats. No uptake of glycerol was observed 3 hours after 45 min pedicle clamping.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501856 TI - [Suppressive effect of methylprednisolone on bovine serum albumin nephritis in mice]. AB - Experiments were undertaken to study whether progressive processes of bovine serum albumin (BSA) nephritis in C57BL/B10-BR mice could be prevented by the treatment with methylprednisolone (MPSL), a glucocorticoid. Crescentic glomerulonephritis could be induced in 22 mice with high 95 per cent reproducibility by preimmunization of 0.2 mg of BSA four times every 2 weeks, followed by daily intraperitoneal injections of 50 mg/kg of BSA for 4 weeks (group IV, a control). In groups of 8 mice each, intraperitoneal injection of 50 mg/kg of MPSL was initiated 3 days before preimmunization (group I), before daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group III). In each group, the treatment was continued until the final day of the experiment. In group I, anti-BSA antibody titers, the levels of circulating immune complexes (CIC) and urinary protein was significantly suppressed in comparison with those in group IV. Histologically, diffuse intra- and extra capillary proliferation observed in group IV was apparently inhibited. In group II and III, urinary protein and intra-/extracapillary proliferation were significantly diminished compared with those of group IV in spite of minor or no decrease in antibody titers and the CIC levels. These results suggest that MPSL has a suppressive effect on the progressive processes of immune complex mediated glomerulonephritis through both its immunosuppressive and antiinflammatory actions, especially when used in the early stage of immune reaction. PMID- 8501857 TI - [HLA haplotypes associated with IgA nephropathy]. AB - Forty-four Japanese patients with IgA nephropathy and their relatives were typed for HLA-A, B, C, DR and DQ antigens and their HLA haplotypes were determined. The frequency of DQ4 increased significantly in the patients as compared with that in 100 healthy control persons (Pc < 0.01). DR4 frequency was higher than in the control subjects but revealed no significant difference (p < 0.05, Pc > 0.05). The incidence of DR4-DQ4 haplotype was increased in the patients (54.5%) and A24Cw-B52DR2DQ1 haplotype which is very common in the Japanese population was decreased as compared with controls of general Japanese population. Thirty-nine cases of 44 (88.6%) had DR4 or DR9 and HLA genotypes of DR4/DR 5, 6, 8 and DR9/DR5, 6, 8 were significantly increased as compared with those in the control subjects (P < 0.001). The incidence of DR4 was significantly higher in the patients with macroscopic hematuria as compared with those without (P < 0.01). No specific HLA antigens or HLA haplotypes were related to the prognosis of IgA nephropathy. These findings suggested that HLA haplotypes associated with DR4 DQ4, DR4-DQ3 and DR9-DQ3 as well as those associated with DR5, 6, 8 might be involved in susceptibility to IgA nephropathy, while A24Cw-B52DR2DQ1 haplotype might be resistant to the disease development. PMID- 8501858 TI - [Evaluation of the localizing procedures of primary aldosteronism]. AB - The validity of preoperative localizing procedures was studied in 36 patients with primary aldosteronism due to adrenal adenoma, all of whom were confirmed surgically. Adrenalectomy resulted in normalization of blood pressure and serum potassium. Furthermore, we reviewed the correlation between mass size and some clinical parameters as well as the accuracy of localization procedures. Adopted localization procedures included imaging techniques such as abdominal ultrasonography, computed tomography (CT), adrenal scintiscan, magnetic resonance imaging (MRI) and adrenal venography, and as a functional diagnostic procedure, adrenal venous sampling. Among imaging procedures, CT was the most effective to detect adrenal mass with as high accuracy as 88%, adrenal venography following with 83%. The correct localization was obtained in 60% by adrenal scintiscan and only 39% by ultrasonography. Although MRI was performed only in 2 cases, the smallest adenoma could be detected only by MRI, suggesting that MRI might be useful to detect microadenoma by increased signal intensity. Although adrenal scintiscan had been considered to be useful because of its functional diagnostic characteristics, the correct localization was as low accuracy as 60%, which was not improved by the administration of dexamethasone. To assess the accuracy of lateralization for adrenal venous sampling, we calculated the ratio of aldosterone concentration in adrenal vein to inferior vena cava. When the ratio was more than 10 or less than 1, the correct localization was made.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501859 TI - [Predictability of creatinine clearance from serum creatinine in chronic glomerulonephritis]. AB - We evaluated the formulas of urine-free prediction of creatinine clearance (CCr) for clinical use in the patients with chronic glomerulonephritis (CGN). Subjects were 246 patients with CGN diagnosed by renal biopsy with range from normal renal function to end stage renal failure. CCr were measured exactly with urine collections more than 2 times and compared with the values calculated using four urine-free mathematical formulas of Cockcroft et al, Mawer et al, Konishi et al, and Tozune et al. Strong, statistically significant correlations were observed between CCr estimated with each prediction method and measured CCr (r > or = 0.946). However, the latter two formulas tended to overestimate the values. Predicted errors more than 20% of the formula of Cockcroft et al, were the least. And their formula was the easiest for clinical use because of the simplicity for learning by heart. We conclude that these four formulas can be used with reasonable accuracy in the patients with CGN from normal renal function to end stage renal failure, and the formula of Cockcroft et al, is the most recommendable for clinical use. PMID- 8501860 TI - [Pneumatosis cystoides intestinalis following steroid treatment in a nephrotic syndrome patient: report of a case]. AB - Pneumatosis cystoides intestinalis (PCI) is a relatively rare, benign condition characterized by multiple subserosal or submucosal gas-filled cysts in the bowel wall. The cause and incidence of PCI are uncertain, but the condition is most commonly diagnosed in patients who have chronic obstructive pulmonary disease, gastrointestinal disease (e.g. Crohn's disease, peptic ulcer disease) or collagen disease (e.g. scleroderma, systemic lupus erythematosus). The report of PCI associated with nephrotic syndrome has not be known as far as we have referred. We first experienced a case of PCI with nephrotic syndrome. The patient was a 28 year-old female who had developed nephrotic syndrome in 1977. Although she had been treated by steroid since the onset of the nephrotic syndrome, she was a frequent relapser. She was hospitalized to our hospital on November 1988, due to fourth relapse of the disease. The increasing dosage of steroid (60mg/day) improved general edema and decreased urinary protein, but abdominal pain and fullness occurred seven weeks after the admission. The abdominal radiographs showed air accumulations in the wall of the intestine (probably right sided colon) and retroperitoneum. That finding was confirmed by Barium enema and abdominal computed tomography. We diagnosed the lesions as PCI from the above findings, and high flow oxygen and hyperbaric oxygen therapy improved the symptom of PCI. The etiology of PCI in this case was thought to be mainly a long term steroid treatment. PMID- 8501861 TI - [Clinical analysis of the factors affecting the prognosis of acute renal failure]. AB - Analysis of the factors influencing the prognosis of acute renal failure was carried out in cases experienced during the past 10 years. The factors presumed directly affecting the renal function (acute insults) and coexistent predisposing factors (risk factors) were analysed. The followings were considered to be acute insults: surgery/trauma/burn, drug intoxication, sepsis, hypotension, dehydration, rhabdomyolysis, hepatorenal syndrome, and hypercalcemia/hyperuricemia. Suspected risk factors included age, urine volume, underlying disorders/complications. Risk factors rather than acute insults were related to the outcome of acute renal failure. The mortality rate increased as the associated risk factors increase in number. In non-oliguric cases, maximum serum creatinine level was lower than the anuric cases, however there was no difference in the duration of the impaired renal function between 2 groups. In survival cases, the factors affecting the time for the recovery of renal function were also studied, but no definite factors could be determined. PMID- 8501862 TI - [Nursing and law. The role of the nurse and the law]. PMID- 8501863 TI - [Survey report on nursing education, 1992]. PMID- 8501865 TI - [A critical review on job characteristics model--a focus on levels of analysis issues]. PMID- 8501864 TI - [Professional power of nurses]. PMID- 8501866 TI - [The legal research method; an approach to enhance nursing science]. PMID- 8501867 TI - [Nursing diagnosis of a child with Reye syndrome approved by North American Nurses Association (based on C-Roy)]. PMID- 8501869 TI - [Nursing and law. Nursing in its legal aspects]. PMID- 8501868 TI - [Development or the nursing productivity conceptual framework]. AB - This study was performed to develop the conceptual framework of the nursing productivity. The study efforts were made: (1) to define the concept the nursing productivity, (2) to identify the elements of the productivity, and (3) to determine the relationship among the elements. With the aim, the study employed a descriptive analysis by way of reviewing various references related to the subject. The nursing productivity consists of such elements as the nursing efficiency and the nursing effectiveness which are complementary to each other. The nursing efficiency is the quantitative input/output ratio, while the nursing effectiveness represents the integrated outcome of such sub-elements as the degree of accomplishing nursing goals, the quality of nursing service, consumer's satisfaction, and the degree of improvement of nurse's attitude toward the quality care. The nursing productivity can be estimated by summing up the nursing efficiency and the effectiveness. By employing the system theory model, the elements of the nursing productivity consist of three elements; the input, the process, and the output. By the process elements, the system inputs are transformed to the system outputs nursing efficiency and nursing effectiveness which are input to the system, in turn, through feedback mechanism (Figure 4). PMID- 8501870 TI - [A study on the establishment of a fee system for hospital based home nursing care]. AB - This study was done in order to provide basic data to a Fee System for hospital based Home Health Care services in Korea in the future. It was done by investigating activities provided to possible Home Health Care clients who could be discharged early from general hospitals and then estimating the nursing care fee according to each nursing activity based upon the time used for activity. The subjects of the study were selected by convenience sampling and consisted of 35 clients who might be clients for Home Nursing Care and were presently admitted to a medical-surgical ward of Y University Medical Center located in Seoul, Korea. The data collection period was from September 1, 1991 to September 30, 1991. The research instruments utilized for the study were a client selection criteria for Home Health Care developed by Choo (1991) and a check-list of nursing activity developed by researcher. The results of the study were as follows: 1. There were 44 different nursing activities provided in the seven days but the time was calculated for only 25 of the nursing activities. 2. Fees for the 25 different nursing activities were calculated by multiplying the median of the average wage of a staff nurse having five years experience in an A grade general hospital to the time of the nursing activity. The results were compared with the insurance fee which the government recognized as an appropriate fee for that activity. The nursing activities with a lower calculated fee than the insurance fee were suction, catheterization, exercise education and dressing change. The nursing activities with a higher calculated fee than the government recognized fee were IM injection and vital sign check. 3. There was a range of 1-15 nursing activities provided daily to the client. For the average number of nursing activities per day of 6.26 events the nursing care fee was calculated at W 6136 per day. 4. Based upon the results of the study, a recommendation for a Home Health Care fee per visit based on the nursing activities provided could be formulated for a Home Health Care fee system. It could be formulated as following: 1) Home health Care fee per visit = [(direct nursing fee (direct nursing care time per activity x average nursing wage) + indirect nursing fee) x average nursing activity per visit] + management fee+materials fee+a travel fee. In this way a nursing fee could be calculated based upon the result of the study of the nursing fees per visit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501871 TI - [An analysis on current status of emergency medical services system of the Seoul area]. PMID- 8501872 TI - [A survey of home health nursing service and satisfaction at a home health agency in UTMB]. AB - The purpose of this study was to describe the population of a Medicare/Medicaid home health agency in Galveston, identify their specific needs and assess their satisfaction with the services provided to them. The data obtained will be used to improve home health services in the Galveston agency. RESEARCH QUESTIONS: 1. What nursing care services are required by home health patients? 2. What needs for other services (e.g. therapy service, homemaker/personal care services, social work services) do home health patients have? 3. What other resources do home health patients currently have to meet their needs? 4. What services do nurses provide during a home health visit? 5. How satisfied are home health patients with services received through the agency? METHODOLOGY: Two types of data were collected for this study. Data relating to patient characteristics, need for services and services provided were obtain by a review of home health records. Data relating to patient satisfaction were obtained by mailing a questionnaire to patients after discharge. Patients still receiving services at the end of the data collection period were sent questionnaires at that time. A convenience sample of all patients receiving care through the agency between January and October of 1991 was used. This was a total of 121 patients. All patients receiving care at this agency meet the Medicare/Medicaid eligibility requirement, i.e. they must be homebound and need skilled nursing services, physical therapy or speech therapy on an intermittent basis. Data were analyzed using descriptive statistics. CONCLUSIONS: This predominantly elderly and low income sample of patients was drawn from an agency serving Medicaid clients, as opposed to an agency serving the home care needs of clients covered by insurance or clients who are self-pay patients. Although chronically ill (often with more than one chronic health problem), these clients seemed to be generally able to care for themselves with only short-term home health assistance. Their most common complaints were sensory loss, decreased mobility and nutritional problem.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8501873 TI - [Quality and cost consciousness in nursing]. PMID- 8501874 TI - [Quality and cost consciousness in nursing?]. PMID- 8501875 TI - [Inservice training: resuscitation. Planning and execution of seminars]. PMID- 8501876 TI - [Inservice training--a pillar of professionalism]. PMID- 8501878 TI - [Transcultural nursing. Part of nursing education?]. PMID- 8501877 TI - [Heinz Furst, departmental nurse. Interview by Eva-Maria Krampe]. PMID- 8501879 TI - [The veil hides the unfamiliar. Women in Islam]. PMID- 8501880 TI - [Family--uncooperative?]. PMID- 8501881 TI - [Disposable materials commissions. Environmental protection is everyone's business]. PMID- 8501882 TI - [Psychosocial problems of stoma patients. How can nurses help?]. PMID- 8501883 TI - [Antiquated concepts? Sin and grace]. PMID- 8501884 TI - [Sexuality in the aged]. PMID- 8501885 TI - [Normal dealings with extraordinary people--no utopia but reality]. PMID- 8501886 TI - [Endoscopic therapy of peptic ulcer hemorrhages]. PMID- 8501887 TI - [Candida infections in intensive care patients from the viewpoint of the microbiologist]. PMID- 8501889 TI - [Complete transparency. Report of experiences with the use of Hydrosorb plus]. PMID- 8501888 TI - [Working with cytostatic agents--what is there to be considered?]. PMID- 8501890 TI - [What use is history?]. PMID- 8501891 TI - Radiation safety in the animal house. PMID- 8501892 TI - Genetic variation within and between strains of outbred Swiss mice. AB - The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr 1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains. PMID- 8501893 TI - Influence of chronic oestrogen treatment on severity of hydronephrosis in inbred DDD mice. AB - It has been reported that mice treated chronically with oestrogen (oestradiol propionate) increase their bladder urine volume. Since inbred DDD mice, particularly male DDD mice, lack a protective mechanism against vesicoureteral reflux (VUR), chronic oestrogen treatment may increase the pressure in the renal pelvis and lead to severe hydronephrosis. The present studies were carried out to confirm this hypothesis. Results of a least-squares analysis of variance showed that the severity of hydronephrosis was more severe after treatment with high doses of oestrogen (1.0 and 5.0 mg/kg/week) in entire and castrated male DDD mice. Hydroureter was also observed in the same groups. Intra-vesicular pressure was 7 to 12 cmH2O higher in mice of these groups than in control DDD mice. High doses of oestrogen had no effect on the kidneys of C57BL/6 mice which showed normal protection against VUR, though it increased bladder urine volume. These findings support the hypothesis that hydronephrosis in DDD mice is caused by an incomplete protective mechanism against VUR. PMID- 8501894 TI - Pseudomonas aeruginosa infection in a Chinchilla lanigera. AB - This report describes a case of Pseudomonas aeruginosa infection in a chinchilla. The affected animal displayed a variety of clinical signs including genital swelling, conjunctivitis, anorexia, weight loss, corneal and oral ulcerations and, most unusually, intradermal pustules which developed 8 days after recovery from the initial illness. The occurrence of these pustules has not been documented previously. PMID- 8501895 TI - Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. AB - Segmented, filamentous bacteria (SFBs) form a group of bacteria with similar morphology and are identified on the basis of their morphology only. The relationships of these organisms are unclear as the application of formal taxonomic criteria is impossible currently due to the lack of an in vitro technique to culture SFBs. The intestine of laboratory animals such as mice, rats, chickens, dogs, cats and pigs is known to harbour SFBs. To see whether this extends to other animal species, intestines from 18 vertebrate species, including man, were examined. SFBs were detected with light microscopy in the cat, dog, rhesus monkey, crab-eating macaque, domestic fowl, South African claw-footed toad, carp, man, laboratory mouse and rat, wood mouse, jackdaw and magpie. These results suggest that non-pathogenic SFBs are ubiquitous in the animal kingdom. Among apparently identical animals, there was considerable variation in the degree of SFB colonization. It is suggested that SFB colonization could serve as a criterion of standardization of laboratory animals. PMID- 8501896 TI - Granule cell type cerebellar hypoplasia in a beagle dog. AB - Cerebellar hypoplasia characterized by severe depletion of granule cells and almost intact Purkinje cells was found in a male 19-month-old beagle dog used in a toxicity study. Microscopically, there was a narrow space lacking granule cells between the row of Purkinje cells and the medulla. Gliosis was not seen in any portion of the cerebellum including this space. No significant changes were seen in the Purkinje cells except for occasional cytoplasmic vacuolation. In the molecular layer and medulla, no histopathological abnormalities were observed. PMID- 8501897 TI - Murine cage density: cage ammonia levels during the reproductive performance of an inbred strain and two outbred stocks of monogamous breeding pairs of mice. AB - The Laboratory Animal Breeders Association guidelines recommend a minimum floor area of 300 cm2 for a monogamous pair of inbred/outbred mice or a trio of inbreds. The mean level of ammonia produced during lactation from BALB/c, TO and CD-1 breeding pairs housed in M2 cages with a floor area of 300 cm2 on Day 4 after cleaning was 30 ppm, 87 ppm and 92 ppm, respectively. All 3 strains of mice, particularly the outbred strains, were subjected to high levels of ammonia as compared with human long-term health and safety occupational exposure limits (25 ppm). However, there is a gradient of ammonia within an M2 breeding cage from the nest (19 ppm), to the food hopper, 77 ppm. By housing CD-1 pairs of mice in RM2 cages which have more than double the floor area of M2 cages (676 cm2), the mean level of ammonia during lactation on Day 4 after cleaning was reduced to 26 ppm. The reproductive performance on inbred/outbred strains of mice has to be equated with cage size (floor area) to maintain acceptable levels of ammonia. It is suggested that the recommended minimum floor areas for breeding mice be reviewed. PMID- 8501898 TI - Levels of alpha2 pregnancy-associated glycoprotein in maternal circulation during pregnancy in the mink. AB - This is the first demonstration of alpha 2-pregnancy-associated glycoprotein (alpha 2-PAG) in the mink. Mink alpha 2-PAG exhibits complete immunological cross reaction with dog alpha 2-PAG when analysed in assays employing antisera against canine alpha 2-PAG raised in rabbits. Alpha 2-PAG was quantitated by rocket immunoelectrophoresis in heparin plasma samples obtained from the peripheral circulation of mink during the breeding season. The plasma levels recorded in male mink were significantly lower (23 AU/ml) than the levels recorded in females at any stage of the breeding period. Very early in the breeding season and 2 weeks after delivery the alpha 2-PAG levels were high (> 200 AU/ml) in the circulation of the female mink. Like alpha 2-PAG in the pregnant bitch, mink alpha 2-PAG concentrations reach a local maximum in mid-pregnancy, and a local minimum at term. PMID- 8501899 TI - Comparison of gavage, water bottle, and a high-moisture diet bolus as dosing methods for quantitative D-xylose administration to B6D2F1 (Mus musculus) mice. AB - Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high moisture bolus was selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2F1 mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery. PMID- 8501900 TI - A method for sampling representative muscular venous blood during exercise in rats. AB - A technique for chronic cannulation of the muscular branch of the femoral vein in the rat is described. The method was validated by the application of vascular corrosion casts and comparative analysis of lactate concentration with mixed venous blood and arterial samples taken through the cannulas during lower hindlimb muscle contraction in anaesthetized rats. PMID- 8501901 TI - Guidelines for the care of laboratory animals in transit. Laboratory Animal Breeders Association of Great Britain Limited (LABA) and Laboratory Animal Science Association (LASA). Association of the British Pharmaceutical Industry (ABPI), British Laboratory Animal Veterinary Association (BLAVA), Institute of Animal Technology (IAT), Ministry of Agriculture, Fisheries & Food (MAFF), Universities Federation for Animal Welfare (UFAW), and Animals (Scientific Procedures) Inspectorate. PMID- 8501902 TI - An animal model for in vivo evaluation of tumor glycolytic rates with positron emission tomography. AB - We developed a method for evaluating tumor glycolytic rates in vivo with nude mice injected with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) and a dedicated animal positron emission tomography (PET) scanner. Animals were injected with NR-6 mouse fibroblast tumor cell lines. When tumors achieved a large enough size to be macroscopically visible, quantitative measurements of FDG uptake in vivo were obtained, using both standard nonlinear regression with the FDG tracer kinetic model to generate estimates of model parameters, including KNLR, the rate constant for net phosphorylation of FDG. Additionally, we determined the values of KPAT, the rate constant for net phosphorylation of FDG measured with a non iterative graphical method. Estimates of K were highly correlated (r = 0.95) with both methods, and parametric images of KPAT demonstrate both the tumor location and size, but are also scaled in units of phosphorylation of FDG. The method is suitable for serial studies of tumor glucose metabolism during and after therapeutic interventions, such as chemotherapeutic trials. PMID- 8501903 TI - Patterns of presentation in brain tumors in the United States. AB - This study included 11,111 cases with confirmed primary brain tumors reported by 679 different hospitals in the United States in 1980 and in 1985. The combinations of symptoms and signs in relation to the site of the brain tumors, supratentorial vs infratentorial, were studied. Only one symptom was present in 32.9% and 26.7% of cases with supratentorial and infratentorial tumors. No neurologic sign was detected at the time of diagnosis in 20% and 14.6% of cases with supratentorial and infratentorial tumors, respectively. Considering the clinical stage at diagnosis, no neurologic sign was detected in 21.4% of patients presenting in stages I and II: compared with 11.5% in those presenting in late clinical stages (III & IV). The study confirmed the importance of meticulous history taking for early referral for diagnosis of brain tumors. PMID- 8501904 TI - The spleen can influence the metastasis of AH130 hepatoma cells in rats. AB - The effect of pathophysiological conditions due to disturbance of the spleen is still unclear. We studied the effects of splenectomy in normal and methylcellulose-induced hypersplenic rats on the development of pulmonary metastases created by intravenous injection of ascites containing AH130 hepatoma cells from male Hos-Donryu rats. Growth of metastatic lesions in the lung was not affected by splenectomy in normal rats, but was increased by splenectomy in hypersplenic rats. Overall, there were fewer pulmonary metastases in rats with hypersplenism, but after splenectomy rats with hypersplenism had a significantly greater number of metastases than did normal rats. The metastases rate correlated somewhat with changes in the blood coagulation and T lymphocyte profile. There is a relationship between the spleen and formation of metastases in cancer. Formation of metastases in the lung was affected most by splenectomy in hypersplenism. To elucidate the mechanism by which metastases are formed in the lung under these pathologic conditions, further studies on the exact role of the spleen are required. PMID- 8501905 TI - Effect of insulin-like growth factor 1 on host response to tumor. AB - Oncology patients suffer multiple detrimental metabolic alterations. Among these are catabolism of tumor free body mass to supply nutrients to feed the tumor. This results not only in enhanced tumor growth but also poor wound healing and immunosuppression of the tumor host. Efforts are therefore being directed at finding methods for improving the nutritional status of the tumor host without enhancing tumor growth. We investigated the ability of two hormones, insulin-like growth factor-1 (IGF-1) and insulin, to improve physiologic function in tumor bearing animals. Tumor-bearing animals received a continuous infusion of IGF-1 (2.20 mg/kg/day), insulin (820 microns/kg/day) or placebo via an osmotic minipump for 7 days. All animals were pair fed to eliminate nutritional intake as a variable. The placebo group lost 31.37 +/- 4.3 g of tumor free body mass during the study period. The insulin treated group lost 26.34 +/- 7.42 g and the IGF-1 group lost 5.07 +/- 3.25 g (P < 0.001, ANOVA). IGF-1 treatment failed to alter plasma glucose, lactate, or total amino acid concentration and failed to alter hepatic ketone body concentrations, but did improve hepatic mitochondria redox potential. Finally, IGF-1 improved splenic weight by 110% and splenic lymphocyte count by 300%. In conclusion IGF-1 appears to offer potential in supporting tumor free host body mass without stimulating tumor growth. PMID- 8501906 TI - Cancer of the male breast: the Turkish experience. AB - Twenty-six patients with male breast cancer who were admitted to the Center of Oncology and Nuclear Medicine, Istanbul, Turkey, between 1980 and 1988, were analyzed retrospectively. Median age was 60 years. Most lesions were infiltrating ductal carcinomas (92%). Of 26 lesions, 9 were staged as stage II (35%), 14 as stage III (54%), and 3 as stage IV (11%). All but five patients underwent unilateral mastectomy (81%). Postoperative treatment consisted of radiation therapy combined with chemotherapy in 11 patients (42%), chemotherapy with or without hormonal therapy in 4 (15%), radiation therapy alone in 10 (38%). Radiation therapy was delivered for a mean total radiation dose of 52 +/- 2 Gy (range 30-60 Gy). Chemotherapy consisted of cyclophosphamide, methotrexate and 5 fluorouracil (CMF) in most patients (60%). FAC regimen (5-fluorouracil, Adriamycin, and cyclophosphamide) was given to 6 patients (40%). Six patients were known to have died of breast cancer during follow-up (23%). Fourteen patients were NED (no evidence of disease) at last follow-up (54%). Overall actuarial 5-year survival was calculated to be 37%, and median actuarial survival was 46.6 months. Actuarial 5-year disease-free survival was 27%, and median actuarial disease-free survival was 47.1 months. Only one patient had a local recurrence, and eight patients had 13 distant metastases (31%). Age (P = 0.023), tumor stage (P = 0.055) and nodal status (P = 0.013) were the most significant prognostic factors correlated with the overall survival. PMID- 8501907 TI - Vaginal melanoma and the role of regional chemotherapy. AB - Vaginal melanoma is a rare cancer usually diagnosed as a locally advanced disease. Aggressive surgical management of the primary tumor and local-regional recurrences, combined with the use of adjuvant radiation and chemotherapy, improves disease-free interval and, perhaps, survival times. Techniques of regional chemotherapy allow the delivery of high doses of chemotherapy to the tumor bed, while minimizing systemic toxicities. These treatments can be used to decrease tumor size, render bulky tumors resectable, and decrease the need for radical procedures. Additionally, they may help eradicate clinically inapparent local-regional disease and have a favorable effect on survival times. PMID- 8501908 TI - Giant cell fibroblastoma. AB - A report of a 1 1/2-year-old male child diagnosed as a case of giant cell fibroblastoma is described and the available literature on this neoplasm is reviewed. The tumor consists of a mixture of spindle cells and multinucleated giant cells in a myxoid or collagenous background. The pathological findings and clinical course suggest that these tumors be classified with fibromatoses of childhood. Removal of the tumor with wide excision is sufficient and these patients do not require any form of chemotherapy. PMID- 8501909 TI - The Tikhoff-Linberg procedure in the treatment of sarcomas of the shoulder girdle. AB - The majority of patients with soft tissue or bone sarcomas of the upper extremity can be treated today with limb-saving procedures using combined modality therapies. For patients with a tumor in the shoulder area, sometimes an interscapulothoracic amputation is the only radical surgical treatment. However, in selected cases, in which the tumor does not involve the neurovascular bundle, a limb-sparing alternative might be the Tikhoff-Linberg resection. Normal function of the hand and forearm, with reasonable function of the elbow, can be maintained by this procedure. Four case histories are reported. PMID- 8501910 TI - Neural cell adhesion molecule (NCAM) and perineural invasion in bile duct cancer. AB - Perineural invasion is associated with tumor spreading and an unfavorable prognosis in a variety of cancers. Recently, neural cell adhesion molecule (NCAM) has been reported to be affinitive to neural tissues, which suggests some relationship between NCAM and perineural invasion. This study was designed to elucidate the role of the expression of NCAM on the development of perineural invasion in bile duct cancer. A histopathologic study was performed on 24 patients with bile duct carcinoma who underwent resections. The overall incidence of NCAM expression in the resected specimen was 66.7% and that of perineural invasion was 87.5%. Furthermore, NCAM expression was shown to be positive in 16 (76%) out of 21 cases in whom perineural invasion was observed. A significant positive correlation was found between the expression of NCAM and perineural invasion in bile duct cancer. These results highlight an important role of NCAM in the development of perineural invasion in bile duct cancer. PMID- 8501911 TI - Soft tissue sarcoma: the enigma of local recurrence. AB - Local recurrence following the treatment of soft tissue sarcoma has been long recognized as a grave prognostic sign. Nevertheless, many investigators have recently suggested that local recurrence following limited surgery ("local persistence") may be a manifestation of a tumor's size and metastatic potential and not a cause of tumor cell dissemination. The author reviewed the experience of several investigators with local persistence. This event was not found to be a threat to survival. The author offers an explanation for this unexpected finding. Soft tissue tumors vary widely in their metastatic potential, and patients also may vary widely in their ability to resist the distant implantation of circulating tumor cells. Patients with a low level of host resistance may be more susceptible to both distant metastases and local persistence, and vice versa. Weaker patients succumb to their initial tumor. Patients who survive the circulating tumor cells from their primary tumor may be immunologically prepared to survive the local persistence of a similar volume of tumor without developing distant disease. PMID- 8501912 TI - Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation. AB - Histological and immunohistological prognostic factors for well-differentiated oral squamous cell carcinoma (SCC) were examined in 31 patients. They included 18 males and 13 females aged 42-84 (median 63) years. The tumors were located in the tongue in 13 cases, gingiva in 7, floor of the mouth in 5, cheek mucosa in 4, and palate in 2. Advanced disease (stages III and IV) was found in 92% of patients; 22 were treated by radical surgery and nine by excisional or incisional biopsy, followed by adjuvant chemotherapy and external radiation. The 5-year survival rate in patients with stages III and IV disease was 58% and 33%, respectively. Histologic factors evaluated were tumor cell mitotic counts, degree of lymphocyte and eosinophil infiltration around the tumor, mast cell counts, HLA-DR expression on tumor cells, or surrounding lymphocytes. Multivariate analysis revealed that degree of eosinophilic infiltration and expression of HLA-DR antigen on the tumor cells were significant factors for prognosis (P < 0.05); i.e., heavy eosinophilic infiltration and expression of HLA-DR antigen on tumor cells were signs of an unfavorable prognosis. The interpretation of the present findings are discussed with a review of the literature. PMID- 8501914 TI - The use of Bayesian analysis of PCR-derived genomic DNA sequences to enable a biologically relevant interpretation of immunoglobulin variable region gene expression. AB - We analyzed by means of polymerase chain reactions (PCRs) and DNA sequencing techniques the immunoglobulin heavy chain variable region genes of bone marrow B lineage cells. We first formulated an explanatory model to guide understanding of the biological mechanisms determining both the size of the total available pool of relevant genes and clonal expansion following heavy chain gene rearrangement. We then followed Box's paradigm of criticism and estimation to interpret our experimental findings. PMID- 8501913 TI - Modeling T cell-antigen presenting cell interactions. AB - We present and analyze a model for the interaction of naive T cells with antigen presenting cells (APCs) that results in T-cell activation. We use this model to examine delayed type hypersensitivity (DTH) reactions. We show that responses can be of two types; either the antigen is completely eliminated or the immune system fails to eliminate the antigen and chronic infection results. Both outcomes are characteristic of diseases in which delayed type hypersensitivity is the primary defense mechanism. We compare the effectiveness of two types of APCs macrophages and dendritic cells, in the generation of DTH responses. We conclude that dendritic cells are more suited to the task of stimulating naive T cells than are macrophages, as has recently been argued by Steinman and coworkers. PMID- 8501915 TI - Epithelial cell detachment in the nephrotic glomerulus: a receptor co-operativity model. AB - Detachment of epithelial cells from the glomerular capillary wall correlates with the massive increase in protein leakage across the capillary wall that is characteristic of many renal diseases. We introduce the hypothesis that this detachment process involves three classes of physical events acting at the subcellular level: the receptor-mediated binding of epithelial cells to basement membrane, the transglomerular hydraulic pressure gradient acting to lift the cells off the basement membrane, and a receptor-receptor co-operativity induced by mechanical deformations of the epithelial cell surface. After presenting the available evidence, we explore the hypothesis by means of a simplified, quantitative model of the detachment process. The model is developed by mapping between the stochastic events of cell adhesion receptor binding and the equilibrium statistical mechanics of the Ising model. Monte Carlo simulations predict cell attachment under normal conditions, as expected from experimental data, and detachment at lower receptor binding affinity and/or increased pressure gradient. The normal attached state in the model is found to be particularly sensitive to changes in the receptor-binding affinity. The amount of resistance the cell surface offers to deformation forces is a key determinant of whether the detachment of small clusters of receptors spreads to involve large areas of the plasma membrane, precipitating bulk detachment. PMID- 8501916 TI - The time allometry of mammalian chewing movements: chewing frequency scales with body mass in mammals. AB - For a sample of 26 extant mammalian species, a significant relationship between body mass and chewing frequency was found, in which chewing frequency is proportional to body mass to the -0.128 power. This relationship is similar to previously published data relating stride frequency and body mass in quadrupedal mammals. It was also found that jaw length is proportional to body mass to the 0.312 power, which is consistent with geometric scaling of jaw length. The period of the chewing cycle was found to be proportional to jaw length to the 0.383 power. These results demonstrate that chewing frequency does not scale as metabolic rate, and support the suggestion that the natural frequency of the chewing rhythm may be derived from masses and lengths of the components of the masticatory apparatus alone. PMID- 8501917 TI - Reaction-diffusion coupling in a structured system: application to the quantitative simulation of endplate currents. AB - An approach derived from reaction-diffusion problems is introduced to describe the synaptic endplate current (EPC) at the neuromuscular junction. The model constructed borrows heavily from earlier models, but it takes into account the anisotropic distribution of the different elements participating to the generation of EPC. The transmitter acetylcholine (ACh) is released at the presynaptic membrane, diffuses through the cleft where acetylcholinesterase is homogeneously distributed and then reaches the postsynaptic surface where the receptor is located. The system is defined by a series of partial differential equations which are solved by an explicit difference method. The model predicts amplitudes and time constants in agreement with those observed experimentally, in all the conditions of inhibition of the enzyme or the receptor tested. PMID- 8501918 TI - Entropic profiles of DNA sequences through chaos-game-derived images. AB - A new method to determine entropic profiles in DNA sequences is presented. It is based on the chaos-game representation (CGR) of gene structure, a technique which produces a fractal-like picture of DNA sequences. First, the CGR image was divided into squares 4-m in size (m being the desired resolution), and the point density counted. Second, appropriate intervals were adjusted, and then a histogram of densities was prepared. Third, Shannon's formula was applied to the probability-distribution histogram, thus obtaining a new entropic estimate for DNA sequences, the histogram entropy, a measurement that goes with the level of constraints on the DNA sequence. Lastly, the entropic profile for the sequence was drawn, by considering the entropies at each resolution level, thus providing a way to summarize the complexity of large genomic regions or even entire genomes at different resolution levels. The application of the method to DNA sequences reveals that entropic profiles obtained in this way, as opposed to previously published ones, clearly discriminate between random and natural DNA sequences. Entropic profiles also show a different degree of variability within and between genomes. The results of these analyses are discussed in relation both to the genome compartmentalization in vertebrates and to the differential action of compositional and/or functional constraints on DNA sequences. PMID- 8501919 TI - Somatic mutation, monoclonality and stochastic models of stem cell organization in the intestinal crypt. AB - Among highly proliferating tissues the intestinal tissue is of particular interest. Techniques are available that permit an insight into how intestinal crypts as the basic macroscopic tissue unit are regenerated from a small population of self-maintaining stem cells. However, neither the precise number of these stem cells nor their properties are known. We have recently suggested a model of stem cell organization which explains the life cycle of murine intestinal crypts, their birth (by crypt fission) and extinction rates, as well as their size distribution on a quantitative basis (Loeffler & Grossman, 1991). The model assumptions involve two stochastic branching processes, one for the growth of several independent indistinguishable stem cells and a second for a threshold dependent crypt fission process. New data have now become available challenging the above concept. They relate to the conversion of crypts to monoclonal phenotypic expression after mutagenic events, presumably taking place in single stem cells. A detailed analysis of these data is shown here utilizing a more elaborate version of the above model. The new data are consistent with this model within the range of parameters predicted previously. We conclude that the cellular regeneration of intestinal crypts can be explained on the basis of several indistinguishable stem cells which can replace each other. PMID- 8501920 TI - Accuracy of tRNA charging and codon: anticodon recognition; relative importance for cellular stability. AB - Cellular homeostasis and the mechanisms which control homeostasis are important for understanding such fundamental processes as ageing and the origin of life. Several models have studied the importance of accurate protein synthesis for cellular stability, but these models have not considered the complexities of the translation process in any detail. Here we develop a new model which describes the interplay between aminoacyl-tRNA (aatRNA) synthetases, the cellular pool of charged tRNAs and the process of codon: anticodon recognition. We also take the processive character of the ribosomes into account. In common with previous work, our model predicts that the cellular translation apparatus can either be stable or deteriorate progressively with time. However, because our model explicitly describes different subreactions of the overall translation process, we are also able to assess the relative importance of accurate tRNA charging and codon: anticodon recognition for cellular stability. It appears that the tRNA charging by the aatRNA synthetases plays the key role in controlling the long-term stability of the cell. Ribosomal errors are less important because error-prone ribosomes, being processive, produce mainly inactive proteins which do not contribute to error propagation within the translation machinery. PMID- 8501921 TI - Circulatory models of intact-body kinetics and their relationship with compartmental and non-compartmental analysis. AB - Circulatory models for interpreting the kinetics of substances in vivo explain the kinetics of the intact body with the concepts of organ kinetics. In this paper, it is first shown that classical organ kinetic analysis is incomplete for metabolized substances, and an appropriate extension is developed. It is then discussed how the concepts of the extended organ kinetic analysis apply to circulatory models. At an organ level, it is shown that two impulse responses are necessary to characterize the organ, one relating influx and outflux, and one relating influx and uptake. The consideration of the inlet-uptake path is of fundamental importance for a correct calculation of the organ volume. It is demonstrated that the total volume is the sum of two components, the first related to the inlet-outlet path, the second to the inlet-uptake path. The first term is computable without assumptions, while the second is model-dependent. Analogous results hold at a total-body level. The relationships between circulatory models and compartmental and non-compartmental analysis are also precisely established. The significance of the non-compartmental estimate of the distribution volume is clarified. The usual strategy of compartmental modeling by which losses are placed in peripheral compartments according to a correspondence between tissues and compartments is shown to be misleading. An example concerning glucose kinetics is given. In conclusion, this paper shows that many of the dominating paradigms of organ and total-body kinetic analysis must be revised. PMID- 8501922 TI - An allelocentric view of life-history evolution. AB - For the case of weak selection, random assortment of gametes, and density independent population regulation, we here establish the conditions under which an allele will spread in a population, with particular reference to the life history effects of the allele, its level of dominance, and sex differences in its effects. Our treatment is simpler than that of Charlesworth (1980), but the results are essentially the same. We show that two quantities govern the selective dynamics of a two-allele single-locus system; these are level of dominance, and the difference between the per copy rates of increase of the alleles in homozygous populations. Our main conclusion is that the eventual outcome of evolution is unaffected by an allele's level of dominance, or sex differences in its effects, provided there is no overdominance. However, speed of progress to fixation is, of course, affected by these factors, and equations are derived to show how level of dominance affects speed of progress to fixation. When a dominant allele only affects the life history of one sex, its rate of spread is half that if both sexes are affected. The relationship between actual and intrinsic rates of increase is discussed and formulae are given showing the relationship for the case of weak selection. PMID- 8501923 TI - A cellular automaton model of cancerous growth. AB - A cellular automaton model describing immune system surveillance against cancer is furnished. In formulating the model, we have taken into account the microscopic mechanisms of cancerous growth, such as the proliferation of cancer cells, the cytotoxic behaviors of the immune system, the mechanical pressure inside the tumor and so forth. The model may describe the Gompertz growth of a cancer. The results are in agreement with experimental observations. The influences of the proliferation rate of cancer cells, the cytotoxic rate and other relevant factors affecting the Gompertz growth are studied. PMID- 8501924 TI - A Darwinian function for the orbital cortex. AB - The relationship between evolutionary theory and human psychobiology suffers from a lack of bridging theory concerning Darwinian brain functions. This problem is addressed within the context of the theory that the human brain calculates Darwinian strategies for the long-term organization of behavior. This theory of brain function is tested using the literature of abnormal psychology, particularly phenotypes that appear to lack strategic evaluation of fitness outcomes. It is argued that sociopaths lack such "fitness-calculation", and therefore their behavior leads to reduced fitness, notwithstanding the absence of psychiatric pathology. Accidental, surgical, and congenital lesions to the orbital cortex of the frontal lobes can produce similar behavior, suggesting that the orbital cortex is the seat of strategic fitness-calculation. This bridge between Darwinian theory and brain function opens the way for formal theories of human behavior couched in terms of imminent Darwinian calculation. PMID- 8501925 TI - Evolutionary stability in the asymmetric war of attrition. AB - It is shown that there are at least two evolutionarily stable strategies, or ESSs, in the war of attrition with a role asymmetry when players make an error with a small but positive probability in implementing their strategy choices. This result proves Maynard Smith's original conjecture that players should choose asymmetric pure strategies in the asymmetric war of attrition. It is also in contrast to the standard non-existence result of an ESS in this game under complete information. To derive this result we discretize the original game and apply the limit ESS condition introduced by Selten. The result is also compared with other evolutionary analyses of this game. PMID- 8501926 TI - On sex ratio and inbreeding in malaria parasite populations. PMID- 8501927 TI - Evolutionary paths in strategy space: an improvement algorithm for life-history strategies. AB - Life-history strategies are analysed using a matrix population model. Within this framework an organism can be characterized at a particular time by a suitable state variable such as age or size, or both. A life-history strategy specifies the action an organism takes in each state. Given a life-history strategy one can find the reproductive value of the various states under this strategy. One can then ask whether an organism following the strategy chooses actions to maximize the reproductive value of itself and its offspring in one year's time. It is shown that if it does not, then a simple procedure identifies a life-history strategy with higher fitness. This strategy-improvement result leads to a necessary and sufficient condition by which (globally) optimal life-history strategies in natural populations can be recognized. We can define two life history strategies to be one step away from each other if they specify the same actions at all states but one. Using this concept one can then define a topology on the phenotypic space of all life-history strategies. The topology taken together with a fitness measure defines the landscape of "strategy space". Results on strategy improvement are used to show that, in contrast to the landscapes usually envisaged for genotype space, strategy space is unimodal: there are no local optima other than global optima, and from every strategy one can reach a global optimum by a non-descending path. PMID- 8501928 TI - Intermolecular forces between the motor protein and the filament. AB - Intermolecular forces between motor proteins and filaments were evaluated on the basis of the experimental data of an in vitro motility assay by considering the molecular friction in the movement system. The molecular friction was caused by a different mechanism from that of the hydrodynamic drag. However, the molecular frictional forces apparently gave the same expression as the hydrodynamic frictional forces. The resulting equation was very effective in examining the physical properties of the weak interaction in the dynein-microtubules system from basic experiments carried out by Vale et al. (1989). From careful analysis of their experimental data, it was concluded that the hydrodynamic friction was not dominant, even in the weak binding state. The electrostatic interaction between dynein-heads and microtubules in the weak binding state was analyzed by applying the DLVO (Derjaguin-Landau-Verway-Overbeek) theory in colloid science through the ionic dependence of one-dimensional diffusion. The interacting distance between charges which took part in the weak adhesion was estimated to be 3 nm. In the present study, the molecular mechanism of the sliding velocity was also investigated for the myosin-actin filaments and the kinesin-microtubules systems by fitting the ATP-dependence and the ionic dependence in ATP-driven active sliding. PMID- 8501929 TI - Infusion of autologous platelet rich plasma does not reduce blood loss and product use after coronary artery bypass. A prospective, randomized, blinded study. AB - Prior nonblinded studies have suggested dramatic hemostatic effects and decreased plasma after cardiopulmonary bypass. Platelet rich plasma (8 to 10 ml/kg total body weight) was obtained (Haemonetics Plasma Saver; Haemonetics Corp., Natick, Mass.) from 51 patients undergoing primary coronary artery bypass grafting before heparinization. After double-blinded randomization, the platelet rich plasma was reinfused immediately in the control group or after heparin reversal in the treatment group. Homologous blood product usage, blood loss, and the surgeon's intraoperative subjective assessment of coagulation were evaluated. Additionally, thromboelastography, prothrombin time, partial thromboplastin time, activated clotting time, fibrinogen, platelet counts, and hematocrit values were evaluated before the operation, after heparin reversal, after infusion of platelet rich plasma or control solution, and 2 hours after infusion. The surgeon's subjective assessment of coagulation was not different between control and treatment groups (p = 0.78). According to specific predetermined transfusion guidelines, no statistically significant differences were found in the use of whole blood (p = 0.07), packed red blood cells (p = 0.62), platelets (p = 0.11), total units of blood products (p = 0.45), or in the percentage of patients receiving transfusions (control group 70%, treatment group 71%, p = 0.97). Cumulative amount of blood shed through the chest tube was not significantly different between the groups at any interval but tended toward significance at 4, 6, and 12 hours (p = 0.09, 0.07, and 0.09). The prothrombin time immediately after reinfusion of platelet rich plasma was significantly lower in the treatment group (p = 0.03), but all other laboratory studies were similar at each time interval. Infusion of platelet rich plasma after cardiopulmonary bypass in patients having uncomplicated primary coronary artery bypass grafting has minimal effects on the surgeon's assessment of coagulation, total transfusion requirements, mediastinal drainage, and laboratory studies of coagulation. PMID- 8501930 TI - The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia. AB - The effects on the postischemic myocardium of amrinone and dobutamine were studied in canine hearts that underwent 90 minutes of hypothermic (10 degrees C) arrested ischemia. In an isolated heart preparation cross-circulated by a support dog, left ventricular pressure-volume loops were collected under a constant afterload based on a mock circulatory system and a range of preload conditions controlled by a computerized servo volume pump. Dobutamine (0, 5, 10, 15 micrograms/kg per minute) and amrinone (0, 0.75, 1.5, 3.0 mg/kg) were tested in this order based on the weights of the support dogs in eight experiments. Changes in intrinsic myocardial contractility were analyzed as percent increases in the preload recruitable stroke work area from baselines. Dobutamine exhibited significant dose-related increases in the preload recruitable stroke work area. Amrinone did not produce significant increases in preload recruitable stroke work area at 0.75 mg/kg; amrinone's inotropic effect was equivalent to dobutamine, 5 micrograms/kg per minute at 1.5 mg/kg, and at the maximum dose (3.0 mg/kg) it was equivalent to dobutamine, 10 micrograms/kg per minute. The myocardial energetic efficiency was determined from the analysis of the myocardial oxygen consumption pressure volume area relationship. The y intercept represents the basal metabolic oxygen requirement of the unloaded beating heart, and the slope is inversely proportional to the rate of energy conversion for increasing loading conditions. Dobutamine significantly increased the y intercepts, but it had no effects on the slopes. These changes demonstrate reduced myocardial efficiencies that are consistent with previous reports. Amrinone (0.75 and 1.50 mg/kg) did not result in change of the y intercepts and the slopes of myocardial oxygen consumption pressure-volume area relationship from baseline conditions. The y intercept was increased with amrinone (3.0 mg/kg), although still not significantly higher than baseline and not to the extents of the dobutamine group. Dobutamine did not have any primary effect on coronary resistance, while amrinone significantly reduced coronary resistance in all loading conditions at 1.5 and 3.0 mg/kg. This study demonstrates that the inotropic effects of amrinone tested under this constant afterload preparation were lower than those of dobutamine. Amrinone has a superior profile of myocardial efficiency on the postischemic myocardium since it does not produce the oxygen-wasting effects of the traditional inotropic agents such as the beta agonists. This benefit, together with amrinone's coronary dilating effects, critically improves the supply/demand ratio that may be of importance in certain clinical situations. PMID- 8501931 TI - Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. AB - The performance of a novel bronchoscopic fluorescence imaging system was compared with conventional white light bronchoscopy with a data base of 328 biopsy confirmed sites from 53 patients and 41 volunteers. The two methods were found to have the same specificity (94%); however, the sensitivity of the fluorescence system (72.5%) was found to be 50% greater than that of the white light bronchoscopy (48.4%) in detecting dysplasia and carcinoma in situ. The fluorescence system uses a nonlinear discriminant function combining the red and green image intensity values to form a pseudoimage that, when displayed on an RGB monitor, allows the detection and delineation of abnormal areas. In 15% of the patients with lung cancer, synchronous carcinoma in situ was found in addition to the large invasive cancer. Of the current smokers in this study, 40% had moderate dysplasia and 12% had severe dysplasia. For the ex-smokers 25% had moderate dysplasia, 6% had severe dysplasia, and 13% had carcinoma in situ. Fluorescence imaging may become an important adjunct to conventional bronchoscopic examination to improve our ability to diagnose and stage lung cancer more accurately. PMID- 8501932 TI - Repair of truncus arteriosus in the neonate. AB - From September 1986 through December 1991, 63 patients with truncus arteriosus underwent surgical repair. The management approach evolved over the period of the study from elective primary repair at 3 months of age to elective primary repair in the early neonatal period. Thirty variables were examined as potential risk factors for the outcome events of death, reoperation, and presence of pulmonary vascular morbidity. According to both univariate and multivariate techniques, severe truncal valve regurgitation, interrupted aortic arch, coronary artery anomalies, and age at repair greater than 100 days were important risk factors for perioperative death. In the 33 patients without these risk factors, early survival was 100%. In the 30 patients with one or more of these risk factors, survival was 63%. Pulmonary hypertensive episodes were fewer, and duration of ventilator dependence and pulmonary artery pressure were significantly less in patients undergoing the operation before 30 days of age. Seven patients required reoperation for right ventricular outflow tract obstruction at a mean follow-up time of 23.4 months, with no deaths. In conclusion, interrupted aortic arch, severe truncal valve insufficiency, coronary anomalies, and repair later than 100 days of age were risk factors for death after repair of truncus arteriosus. In the absence of these associations, truncus arteriosus can be repaired with excellent surgical outcome in the neonatal and early infancy period. Repair in the early neonatal period reduces the prevalence of postoperative pulmonary vascular morbidity. PMID- 8501933 TI - Results of a policy of primary repair of truncus arteriosus in the neonate. AB - Although the early mortality for repair of truncus arteriosus has decreased in the modern era, routine correction in the neonate has not been widely adopted. To assess the results of our protocol of early repair, we reviewed 46 neonates and infants undergoing repair of truncus arteriosus at the University of Michigan Medical Center from January 1986 to January 1992. Their ages ranged from 1 day to 7 months (median 13 days) and weights from 1.8 kg to 5.4 kg (mean 3.1 kg). Repair was performed beyond the first month of life in only 8 patients, because of late referral in 7 and severe noncardiac problems in 1. Associated cardiac anomalies were frequently encountered, the most common being interrupted aortic arch (n = 5), nonconfluent pulmonary arteries (n = 4), hypoplastic pulmonary arteries (n = 4), and major coronary artery anomalies (n = 3). Truncal valve replacement was performed in 5 patients with severe regurgitation, 3 of whom also had truncal valve systolic pressure gradients of 30 mm Hg or more. The truncal valve was replaced with a mechanical prosthesis in 2 patients and with a cryopreserved homograft in 3 patients. Right ventricle-pulmonary artery continuity was established with a homograft in 41 patients (range 8 mm to 15 mm), a valved heterograft conduit in 4 (range 12 mm to 14 mm), and a nonvalved polytetrafluoroethylene tube in the remaining patient (8 mm). There were 5 hospital deaths (11%, 70% confidence limits 7% to 17%). Multivariate and univariate analyses failed to demonstrate a relationship between hospital mortality and age, weight, or associated cardiac anomalies. Only 1 death occurred among 9 patients with interrupted aortic arch or nonconfluent pulmonary arteries. Hospital survivors were followed-up from 3 months to 6.3 years (mean 3 +/- 0.4 years). Late noncardiac deaths occurred in 3 patients, all within 4 months after the operation. Actuarial survival was 81% +/- 6% at 90 days and beyond. Despite the prevalence of major associated conditions, early repair has resulted in excellent survival. We continue to recommend repair promptly after presentation, optimally within the first month of life. PMID- 8501934 TI - Anatomic correction of atrioventricular discordance. AB - Between June 1989 and September 1991, 11 patients underwent anatomic correction of atrioventricular discordance. Their ages at operation ranged from 1 to 11 years (mean 6.7 years) and their weights ranged from 7.1 to 31.8 kg (mean 19.1 kg). Atrial situs was solitus in nine and inversus in two patients. Ventriculoarterial connection was discordant in five and was double-outlet right ventricle in six patients. Associated congenital heart defects were seen in all patients, including 10 with ventricular septal defect, eight with atrial septal defect, nine with pulmonary stenosis or pulmonary atresia, seven with tricuspid regurgitation, and four with mitral regurgitation. Five patients had prior Blalock-Taussig shunts. One patient with an intact ventricular septum had repeated pulmonary banding. Anatomic correction consisted of the Senning and Rastelli procedures in three, the Mustard and Rastelli procedures in five, the Senning and arterial switch operations in two, and the Mustard and arterial switch operations in one patient. In addition, mitral valvuloplasty or valvular annuloplasty was performed in three patients. We did not encounter kinking or torsion of the translocated coronary arteries in our three patients with the arterial switch operation. There was one surgical death. The other patients pursued satisfactory postoperative courses (mean follow-up period of 12.6 months). We recommend that anatomic correction for atrioventricular discordance should be indicated, especially in patients with any sign of systemic right ventricular dysfunction. PMID- 8501935 TI - Initial experience with the maze procedure for atrial fibrillation. AB - From January 1991 until May 1992, a total of 14 patients (mean age 48 years) underwent the maze procedure for refractory atrial fibrillation (mean duration, 7 years; mean number of antiarrhythmic medications, six). Three patients had had embolic events, one patient had had a cardiac arrest from flecainide, one had pulmonary fibrosis from amiodarone, and six of ten who were employed were temporarily disabled. Two patients underwent successful mitral valve repair in which the maze procedure was added as a secondary goal of the operation. Postoperative fluid retention was a problem in five patients (36%). Six patients (43%) were temporarily treated with an antiarrhythmic medication. Two patients (14%) with preoperative sick sinus syndrome required pacemakers. One patient was discharged from the hospital but died suddenly less than 1 month after the operation (7% operative mortality) of hyperkalemia caused by acute renal failure. All patients beyond 3 postoperative months (100% "cure") are receiving no antiarrhythmic medications, have sinus rhythm, or have p-wave tracking with ventricular pacing. Atrial contraction has been documented by cinegraphic magnetic resonance imaging studies and by Doppler echocardiography performed when sinus rhythm had resumed. The maze procedure is an extensive operation but is indicated for selected patients who have the severe sequelae of atrial fibrillation. PMID- 8501936 TI - Clinical evaluation with exercise performance in twenty patients who underwent coronary artery bypass grafting with both the gastroepiploic and internal thoracic arteries. AB - Postoperative exercise performance was evaluated in 20 patients who underwent complete coronary revascularization with simultaneous right gastroepiploic artery and internal thoracic artery grafts for ischemic heart disease and exhibited patency of all grafts on postoperative angiograms. Three patients received only arterial grafts, and 17 simultaneously received a saphenous vein graft. Forty five right gastroepiploic artery grafts were harvested during this study, but two were not used because of foci of severe calcification. The right gastroepiploic artery was grafted to the distal right coronary artery in 17 patients and to the distal obtuse marginal branches in three patients, accompanied by an internal thoracic artery graft to the left anterior descending artery in seventeen, to the diagonal branch in three, and to the proximal right coronary artery in one patient. A postoperative exercise test with a bicycle ergonometer was administered 6 to 12 weeks after the operation, and the results are reported after conversion into metabolic units. The preoperative exercise test resulted in 3.6 +/- 1.9 metabolic units for 18 patients tested, and the postoperative metabolic units were 7.8 +/- 1.3 for 20 patients. Left ventricular wall motion was analyzed by regional ejection fraction before and after coronary artery bypass grafting in 14 patients who received an right gastroepiploic artery graft for the right coronary system. The mean regional ejection fraction of the posterobasal or diaphragmatic wall was 28.0% or 28.2% before operation and improved to 43.1% or 43.2% after coronary artery bypass graft, respectively. The flow of right gastroepiploic artery seemed to distribute adequately to the revascularized area. Long-term results have not yet been proved; the use of simultaneous right gastroepiploic artery and internal thoracic artery grafts, however, thus produced excellent results, as seen from improvements in both left ventricular wall motion and early postoperative exercise performance. PMID- 8501937 TI - Inhibition of adenosine deaminase and nucleoside transport. Utility in a model of homograft cardiac valve preimplantation processing. AB - Human cardiac valves are increasingly used in the reconstruction of ventricular outflow tracts and offer performance advantages over porcine and mechanical prostheses; the durability of these replacements has been associated with leaflet interstitial cell viability and a presumed sustained function after implantation. Preimplantation tissue preparation entails sequential steps that are potentially cytotoxic and may therefore affect functional cell survival at thaw. We defined the metabolic consequences of each interval using semilunar cusps from 118 porcine valves to model a homograft preparation with 40 minutes of fixed cadaveric (harvest) ischemia. Fifty-eight valves served as controls and were first processed according to standard cryopreservation protocol; nucleosides were extracted at the end of each step to differentiate independent contributions to high-energy phosphate depletion. Sixty simultaneously harvested leaflets were administered the nucleoside transport inhibitor p-nitrobenzy-thionosine (NBMPR) and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) at procurement, to attempt adenosine salvage and restitution of processing incurred adenine nucleotide losses. High-performance liquid chromatography was used to compare adenosine triphosphate, diphosphate, and monophosphate and diffusible nucleopurines of the control and EHNA/NBMPR-treated groups. Control results indicate that disruption of the adenosine triphosphate-diphosphate cycle occurs independently with antibiotic disinfection and cryopreservation. However, throughout all preparation steps, adenine nucleotides were maintained at harvest (baseline) concentrations in the EHNA/NBMPR valves. This suggests that salvage therapy may protect a significant number of cells from net high-energy phosphate catabolism. If, with further study, the durability of transplanted valves is concluded to benefit from retained leaflet interstitial cell viability, such enhancement of metabolic tolerance to the obligatory processing may facilitate functional recovery. PMID- 8501938 TI - Prosthetic valve endocarditis with ring abscesses. Surgical management and long term results. AB - From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7%). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% +/- 8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good. PMID- 8501939 TI - Effects of hypoxia on intracellular calcium and contractility. PMID- 8501940 TI - Dysphagia lusoria. PMID- 8501941 TI - Particle-induced coronary vasoconstriction: the need for in-line filtration of cardioplegic solutions. PMID- 8501942 TI - Leiomyosarcoma of the lung. PMID- 8501943 TI - Prostaglandin E1 for patients who have both heart and lung failure after cardiotomy. PMID- 8501944 TI - Dilating effects of isosorbide dinitrate on diameter of internal thoracic artery graft. PMID- 8501945 TI - Lengths of different routes for esophageal replacement in a white population. PMID- 8501947 TI - An economic analysis of heart-lung transplantation. Costs, insurance coverage, and reimbursement. AB - Rarely has the cost of heart-lung transplantation received attention. Although the procedure is still largely regarded as experimental, this does not diminish the significance of costs. The National Cooperative Transplantation Study was undertaken to better understand the costs of all transplants, including heart lung transplantation. Data on transplantation charges from date of procedure to discharge were obtained from more than 65% of all heart-lung transplantation programs active in 1988. These programs accounted for 61% of all transplantations performed in 1988. Valid sample survey data (no more than 25 procedures per center) were obtained for 42 patients, or approximately 58% of all procedures done in the United States. Detailed data were also collected on sources of payment and amount reimbursed. Because of outlier data, we report statistical medians, rather than means, as our measure of central tendency. The median charge for heart-lung transplantation was $134,881, with an average hospital stay of 31 days. Total charges fell between $99,535 and $216,639 for 50% of the cases studied. Half of the patients spent between 23 and 49 days in the hospital. Because of the small number of cases available for analysis, it was not meaningful to cross-classify the data according to various prognostic variables. More than 78% of the procedures studied were paid for by private insurers. Reimbursement exceeded 90% of billed charges for 84.6% of the cases analyzed. Despite the experimental status of heart-lung transplantation, insurance reimbursement has been favorable for those heart-lung transplantations that insurers have covered. Nevertheless, the future of heart-lung transplantation is unclear. The availability of donors remains a serious constraint, as is seen in the decrease of procedures performed annually. In fact, lung transplantation now appears to be the preferred approach to the treatment of pulmonary disease. PMID- 8501946 TI - Improved ultrastructural lung preservation with prostaglandin E1 as donor pretreatment in a primate model of heart-lung transplantation. AB - Donor pretreatment with prostaglandin E1 as a pulmonary vasodilator has developed as a simple, effective means to provide excellent preservation in heart-lung transplantation. This study was undertaken to investigate the degree of ultrastructural preservation of the lung with prostaglandin E1 and other pulmonary vasodilators in a primate heart-lung transplantation model. Heart-lung transplantation was performed in 14 African green monkeys. Donor cardiac preservation was achieved with cold crystalloid cardioplegic solution (10 ml/kg). Lung preservation was achieved with cold, modified Euro-Collins solution delivered into the main pulmonary artery (60 ml/kg total). Vasodilator agents were administered intravenously 15 minutes before aortic crossclamping. The heart lung grafts were stored at 4 degrees C for 6 hours. Three groups of animals were studied: five donors with prostaglandin E1 (0.1 to 4.0 micrograms/kg per minute), five donors with prostacyclin (0.1 to 0.35 micrograms/kg per minute), and four donors with nitroprusside (0.8 to 5.0 micrograms/kg per minute). After transplantation, arterial blood gas measurements and lung biopsies were performed at 1- and 3-hour intervals. Five formalin blocks per specimen were sectioned for hematoxylin and eosin staining. Cellular preservation and endothelial cell swelling were evaluated with electron microscopy. The specimens were graded for alveolar hemorrhage, endothelial cell swelling, and cellular preservation (grade 0, minimal, to grade 3, severe) and a mean score was obtained for each preservative agent. Prostaglandin E1-treated specimens demonstrated the least amount of endothelial swelling (mean score of 1.0) compared with prostacyclin- and nitroprusside-treated specimens (mean scores of 1.4 and 2.7, respectively). All nitroprusside-treated specimens demonstrated moderate to severe endothelial cell swelling. Interstitial and alveolar hemorrhage was noted in poorly preserved specimens, but there were no significant differences between groups. We conclude that prostaglandin E1 provides improved cellular preservation by decreasing the extent of endothelial cell swelling as observed on electron microscopy. PMID- 8501948 TI - Time-course of free radical activity during coronary artery operations with cardiopulmonary bypass. AB - Myocardial and pulmonary impairment after cardiopulmonary bypass may be caused by oxygen free radicals produced by reperfusion and by activated neutrophils. Free radical activity was assessed by assays for lipid peroxidation (thiobarbituric acid-reactive material) and phospholipid-esterified diene conjugation (18:2[9,11]/18:2[9,12] molar ratio) in 25 patients during coronary artery operations. Arterial blood samples were obtained before, during the ischemic period, and for 24 hours thereafter. There were no significant changes in free radical indices during the ischemic periods, but after cessation of bypass they increased significantly. Ten minutes after bypass thiobarbituric acid-reactive material rose from 96 (median; range 65 to 145) nmol/gm albumin to 138 (85 to 200) nmol/gm albumin (p < 0.001), and molar ratio rose from 2.23% (0.45% to 7.70%) to 2.51% (0.39% to 7.93%) (p < 0.02). Values of thiobarbituric acid reactive material subsequently decreased, but molar ratio reached a peak at 4 hours after bypass, 2.64% (0.55% to 10.08%) (p < 0.001), thereafter returning to baseline. The postoperative increases in thiobarbituric acid-reactive material and in molar ratio were correlated (r = +0.53; p = 0.006). These increases in thiobarbituric acid-reactive material and in molar ratio were not related to age, preoperative left ventricular function, or the number of grafts performed. Increase in thiobarbituric acid-reactive material correlated with the duration of cardiopulmonary bypass (r = +0.43; p = 0.03). In 10 patients in whom cardiopulmonary bypass was performed using a bubble oxygenator, the increases in thiobarbituric acid-reactive material were significantly greater than in the 15 in whom a membrane oxygenator was used (p < 0.02). These data show that after apparently uncomplicated coronary operations with bypass there is an increase in lipid peroxidation and diene conjugation, indicating increased free radical activity. This increase varies between patients and does not relate to patient or surgical factors but may depend on the type of oxygenator employed during bypass. PMID- 8501949 TI - The optimal glucose concentration for intermittent cardioplegia in isolated rat heart when added to St. Thomas' Hospital cardioplegic solution. AB - The purpose of this study was to determine the mechanisms by which high physiologic concentrations of glucose (11 mmol/L) were protective while even higher concentrations (20 or 50 mmol/L) were harmful when added to St. Thomas' Hospital No. 2 cardioplegic solution. We evaluated the recovery of isolated working rat hearts subjected to 3 hours of hypothermic multidose cardioplegic arrest. The addition of glucose 11 mmol/L was associated with better aortic flow (79.2% +/- 1.3%) than the addition of glucose 1 mmol/L (61.7% +/- 2.7%), 20 mmol/L (73.6% +/- 1.1%), or 50 mmol/L (66.0% +/- 3.2%) (p < 0.01 versus glucose 1 and 50 mmol/L). An increase in glucose concentration from 1 to 50 mmol/L progressively augmented glucose flux from 2.2 +/- 0.33 to 10.4 +/- 0.79 mumol/gm per 3 hours (p < 0.01), but higher glucose concentrations of 20 and 50 mmol/L inhibited glycogenolysis (p < 0.05 versus glucose 1 and 11 mmol/L), so that total glycolysis was decreased and consequently glycolytic adenosine triphosphate production was reduced from 35.9 +/- 0.47 (glucose 11 mmol/L) to 27.5 +/- 1.25 mumol/gm per 3 hours (glucose 50 mmol/L) (p < 0.01). The end products of glycolysis (lactate and protons) did not appear to affect the recovery of the hearts, because both lactate efflux and tissue lactate were highest in the presence of glucose 11 mmol/L and the pH of the cardioplegic effluent was more alkalotic in glucose 11 and 20 mmol/L. Thus a high physiologic concentration of glucose (11 mmol/L) in the cardioplegic solution improved recovery because of an increased glycolytic adenosine triphosphate production during cardioplegic arrest, whereas even higher concentrations of glucose inhibited these effects. PMID- 8501950 TI - Acupuncture treatment of functional non-ejaculation: a report of 70 cases. PMID- 8501951 TI - 225 hiccup cases treated with electromagnetic impulses at erzhong point. PMID- 8501952 TI - A study on the clinical effect and immunological mechanism in the treatment of Hashimoto's thyroiditis by moxibustion. AB - 71 cases of Hashimoto's thyroiditis were treated by moxibustion and their immune function and thyroid function were observed. It was found that moxibustion was able to reduce the thyroid antibodies in the peripheral blood of the patients with hypothyroidism and to recover their thyroid function. It was also found that moxibustion could lower the thyroid antibody secretory levels and ADCC (antibody dependent cell-mediated cytotoxicity) activities of the lymphocytes. In addition, the action of moxibustion in reducing the secretion of thyroid antibodies was related to its action of regulating the proportions of T lymphocyte subsets. The results indicate that the treatment of Hashimoto's thyroiditis by moxibustion is probably accomplished through its effect in regulating the relationship among the T lymphocyte subsets. PMID- 8501953 TI - Treatment of 1000 cases of lumbar soft tissue injury with acupuncture plus exercise. PMID- 8501954 TI - Simple obesity and obesity hyperlipemia treated with otoacupoint pellet pressure and body acupuncture. AB - 161 cases of simple obesity with or without hyperlipemia were treated by pellet pressure on auricular acupoints plus body acupuncture for 3 months in a single blind experiment. Patients on Capsulae Olei Oenothera Erythrosepalae were taken as positive controls. Body weight, circumference of chest, abdomen, arms and legs, the appetite, sleep, bowel movement, blood TC, TG and HDL-C were recorded for comparison. The results indicated that treatment in the auricular and body acupoint group was superior to treatment in the control group. In the acupoint group body weight dropped by an average of 5.04 kg in 84.55% of the patients, who also showed decreased appetite, blood TC and TG. PMID- 8501955 TI - Observations on the treatment of 393 cases of obesity by semen pressure on auricular points. PMID- 8501956 TI - Acupuncture treatment of 139 cases of neurodermatitis. PMID- 8501958 TI - Observations of the effect of otoacupoint pressure on the motor functions of the gallbladder. PMID- 8501957 TI - Clinical and experimental studies of JPYS in reducing side-effects of chemotherapy in late-stage gastric cancer. AB - This article reports a research project undertaken for more than 16 years by the Cancer Department of Guang An Men Hospital. Tonic Jian Pi Yi Shen (JPYS), which nourishes the spleen and kidney, was used in combination with chemotherapy in the treatment of late stage gastric cancer patients for the purpose of promoting completion of the chemotherapeutic course, improving the general condition, ameliorating the reaction in the digestive system, protecting hemopoiesis and strengthening immunocompetence. The results of lab experiments were found to coincide with those of clinical application. PMID- 8501959 TI - Clinical application of medicinal-bar therapy. PMID- 8501960 TI - External application of drugs: absorption and mechanism. PMID- 8501961 TI - Acupuncture therapy for 12 cases of cranial trauma. PMID- 8501962 TI - Clinical observations on the treatment of 98 cases of peptic ulcer by massage. PMID- 8501963 TI - Treating dislocation of small joints of thoracic vertebrae by manipulation with palm pressing and shaking. PMID- 8501964 TI - Keep-fit massage for health preservation (4). PMID- 8501965 TI - Current applications of acupuncture by otorhinolaryngologists. PMID- 8501966 TI - Acupuncture and moxibustion in the treatment of dermatoses. PMID- 8501967 TI - Inhibition of proliferation of human leukaemia 60 cells by methylglyoxal in vitro. AB - Methylglyoxal (2-oxopropanal) is the physiological substrate of the glyoxalase system. When exogenous methylglyoxal (50 microM-1 mM) was added to human leukaemia 60 (HL60) cells in culture (5 x 10(4) cells/ml), inhibition of growth and toxicity was induced. The median growth inhibitory concentration IC50 value was 238 +/- 2 microM. There was little differentiation of HL60 cells induced by methylglyoxal (a maximum of 2% differentiation with 500 microM methylglyoxal). There was no similar toxicity induced by methylglyoxal in corresponding differentiated cells, neutrophils, under the same culture conditions. Cell growth and toxicity induced by methylglyoxal (250 microM) in HL60 cells occurred in the initial 24 h of culture, after which residual surviving cells exhibited normal growth kinetics. It could also be prevented by replacing the culture medium in the initial 6 h of culture; thereafter, irreversible toxicity developed, reaching the maximum value after 24 h of culture. Growth arrest and toxicity induced by methylglyoxal increased with increasing serum composition of the medium. The mechanism of toxicity is unknown. PMID- 8501968 TI - Blood responses under chronic low daily dose gamma irradiation: II. Differential preclinical responses of irradiated female dogs in progression to either aplastic anemia or myeloproliferative disease. AB - Female beagle dogs were chronically exposed to low daily doses of 60Co gamma rays (7.5 cGy day-1) and responded in one of three distinct hemopathological patterns. These patterns, reflective of distinct subgroups, were characterized by (a) low radioresistance resulting in progressive hematopoietic suppression, terminal aplastic anemia (AA), and relatively short (< 400 days) survival (-S-AA subgroup); (b) high radioresistance, initially coupled with strong but aberrant regenerative hematopoiesis, and later with the development of myeloproliferative disease (MPD) ((+)-R-MPD subgroup); and (c) high radioresistance, coupled with an early phase of strong regenerative hematopoiesis, but later with no myeloproliferative disease (+R-nonMPD subgroup). In this study, the changes in circulating blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes and platelets) were sequentially assessed in time and fitted to a flexible, quadratic-linear-type response model previously developed. These analyses provided definition to (a) an initial suppressive, radiotoxic phase and (b) the subsequent recovery phase for each of these subgroups. The magnitude and severity of blood cell loss during the initial suppressive phase was generally greatest in the -S-AA subgroup and lowest in the +R-nonMPD subgroup, with the +R-MPD subgroup showing intermediate level responses. A notable exception included a very high net loss of blood granulocytes by the +R-nonMPD subgroup relative to the other two subgroups. By contrast, the magnitude of blood cell restoration, as well as blood cell maintenance levels during the secondary, recovery phase, was generally highest in the +R-MPD subgroup, of intermediate strength in the +R-nonMPD subgroup, and extremely weak or absent in the -S-AA subgroup. Notable exceptions were in the +R-nonMPD subgroup's high recovery rates of monocyte and lymphocyte blood levels, as well as the high maintenance levels of blood granulocytes during recovery. These results are consistent with our earlier observations of blood responses of chronically irradiated male dogs, in that subgroups of female dogs prone to specific radiogenic hematopathologies (i.e. AA and MPD) can be readily identified and staged in specific preclinical periods by a series of marked differential blood responses. PMID- 8501969 TI - Proposal for a classification of acute myeloid leukaemia based on plastic embedded bone marrow biopsy sections. AB - Traditional approaches to haematological diagnosis of acute myeloid leukaemia (AML) include microscopic examination of peripheral blood (PB) and bone marrow (BM) cells studied in Romanowsky-stained, dry film smears. The routine evaluation of BM aspirates, however, may be disappointing in accurately assessing marrow activity because of the sampling error inherent in the BM aspiration technique, and occasionally may fail to provide a precise diagnosis because BM aspirates cannot be obtained due to packed or fibrotic marrows. Because of the advantages it offers over the conventional method of diagnosis, we have studied Romanowsky stained, thin sections of plastic-embedded BM biopsies from 87 newly diagnosed AML patients. Based on our study, the patients were broadly grouped into four categories: (1) those with hypocellular marrow (haemopoietic cellularity less than 50%), hypoplastic AML; (2) those with some degree of marrow fibrosis, AML with marrow fibrosis; (3) those with homogeneous infiltration of marrow with blast cells; and (4) those with inhomogenous infiltration of marrow with blast cells. Our results show that the proposed classification of AML based on the evaluation of plastic-embedded BM biopsy sections may offer benefits over those afforded by conventional morphologic smear techniques. This may provide significant prognostic information and may have a major impact on patient management. It may also provide a meaningful stratification of the patient population when comparing treatment protocols for newly diagnosed AML patients. PMID- 8501970 TI - Stimulation of HTLV-I expression by subtoxic dose of 3-methylcholanthrene. AB - In vivo infection by HTLV-I is characterized by the lack of virus expression in the host's infected cells and in most cases it is clinically inapparent. The present study shows that exposure of HTLV-I-infected human T-cells to a maximal non-toxic dose of 3-MC remarkably enhances virus expression. This stimulatory effect was demonstrated by showing elevated levels of viral RNA and proteins within the cells and increased virus release to the culture medium. The enhanced virus expression was found to increase the ability of the treated cells to infect normal human peripheral lymphocytes in co-culture. Such data point to the possibility that initiation of a pathogenic process in HTLV-I-infected individuals might result from activating the expression of the latent provirus by environmental carcinogens. PMID- 8501971 TI - Exacerbating factors of radiation-induced myeloid leukemogenesis. AB - The spontaneous incidence of myeloid leukemia in female mice was slightly higher than in male mice, whereas the radiation-induced incidence was significantly lower than in male mice. We also examined whether the incidence of myeloid leukemia was related to inflammatory response. Mice had a piece of cellulose acetate membrane inserted into the peritoneal cavity to cause inflammation. This did not affect the incidence of myeloid leukemia in unirradiated mice at all, but in 2.84 Gy irradiated mice the incidence (35.9% in male, 26.0% in female mice) increased significantly compared with irradiated-only mice (23.9% and 12.0%, respectively). From these results, the physiological fluctuation of humoral factors by means of inflammatory response is considered to increase the development of radiation-induced myeloid leukemia. PMID- 8501972 TI - Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia. AB - Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia. PMID- 8501973 TI - Lymphoblast colony-culture assay in acute lymphoblastic leukemia: a quantitative approach. AB - Lymphoblast colony-culture of adult acute lymphoblastic leukemia (ALL) was studied to explore its clinical implication. Among 13 marrow cultures from ALL patients with full-blown disease, 11 developed leukemic colonies. A type of colony, very similar to a lymphoblastic colony and possibly T-cell in origin, could be found in four cultures of the six control marrows. To minimize the difficulty in differentiating a leukemic blast colony and a normal lymphocyte colony, based solely on morphology, a quantitative approach was used. Since both the mean of blast colony count and the mean of blast percentage of leukemic marrow were significantly higher than those of the control group, mean value plus two standard deviations of the control group were defined arbitrarily as upper normal limits. The defined normal range was then used to examine the relationship between results of the cultures and clinical outcome for the ALL patients. Early relapse or incomplete remission following chemotherapy could be predicted in four patients by these quantitative colony-culture assays 0.5-2 months before full blown disease. The low colony count and low blast percentage in the colony culture assay of the fifth patient is compatible with the clinical observation of continuous remission. One culture, growing clusters only, had an increased blast percentage; this correlated well with cytogenetic relapse two months later. In summary, the quantitative colony-culture assay could detect morphologically unidentifiable leukemic cells in ALL patients with early relapse or incomplete remission. This quantitative colony-culture system, though not ultrasensitive in the detection of minimal residual leukemic cells, was of potential value as a prognostic assay. PMID- 8501974 TI - Clonal haemopoiesis following cytotoxic therapy for lymphoma. AB - Patients successfully treated for lymphoma by conventional cytotoxic therapy are at increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia. In this study we have investigated a group of haematologically normal females in remission from lymphoma for evidence of clonal haemopoiesis as a possible marker for the development of clonal haemopoietic disorders. Unilateral X-inactivation, and hence clonality, can be determined in females heterozygous for X-linked restriction fragment length polymorphisms by differences in methylation between active and inactive X-chromosomes. We have studied methylation patterns at the DXS255 locus and the phosphoglycerate kinase (PGK) gene in 25 females in remission from lymphoma and compared them to 35 normal females. Unilateral X-inactivation was detected in 4/15 patients in remission from lymphoma versus 2/27 normals at the DXS255 locus and in 4/13 treated lymphoma patients versus 0/11 normals at the PGK locus. Six individuals were analysed by both techniques with complete concordance. Unilateral X inactivation was more common following cytotoxic therapy for lymphoma (7/25) than in normals (2/35) (p < 0.025) and in the lymphoma cohort was associated with increasing time from the end of therapy (p = 0.03). Patients in remission from lymphoma have an increased incidence of clonal haemopoiesis compared to normal individuals. This may be due to either the clonal expansion of an abnormal genetically damaged stem cell or a variation of normal haemopoiesis. Prospective studies will establish whether this finding is associated with an increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia. PMID- 8501975 TI - The methylation status of the major breakpoint cluster region in human leukemia cells, including Philadelphia chromosome-positive cells, is linked to the lineage of hematopoietic cells. AB - The Philadelphia (Ph) translocation [t(9;22)(q34;q11)] is the most common genetic abnormality in human leukemia; a transposition of the ABL gene to the major breakpoint cluster region (M-BCR) is associated with the pathogenesis in Ph+ chronic myelogenous leukemia (Ph+ CML) and in some cases of Ph+ acute leukemia (Ph+ AL). Our current understanding of the methylation of human genomes allows us to consider the association between the epigenetic phenomenon and the control of differentiation and proliferation in mammalian cells. In order to determine whether the methylation status of the M-BCR is associated with breakpoint localization in this region and with the lineage of hematopoietic cells, we have examined 28 patients with Ph+ leukemias, including nine with Ph+ AL, six patients with acute myeloblastic leukemia without Ph (Ph- AML), and five patients with Ph- acute lymphoblastic leukemia (Ph- ALL); using the restriction endonuclease isochizomers, MspI and HpaII. In CML patients in the chronic phase, the hypomethylated status within the normal M-BCR allele is heterogeneous. In contrast, patients with Ph+ CML in the lymphoid blast crisis phase exhibited a 2.5/2.7 kb band with a complete disappearance of the germline M-BCR fragment (type L). This pattern is consistently noted in Ph- ALL cells, and the pattern is quite different from that found in myeloid blast crisis or Ph- AML (type M). In patients with M-BCR-nonrearranged Ph+ ALL, it is suggested that the M-BCR methylation patterns are cell-lineage specific but some Ph+ ALL cells had a hypomethylation pattern that was identical to that observed in Ph- AML, suggesting a distinction of genetic diversity of leukemia cells with the Ph chromosome, especially Ph+ AL. PMID- 8501976 TI - Serum levels of a negative regulator of cell proliferation (AcSDKP) are increased in certain human haemopathies. AB - One of the first known effects of the endogenous peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) is to inhibit entry into DNA synthesis of pluripotent haematopoietic stem cells (CFU-S) in mice. A specific anti-AcSDKP polyclonal antibody allows the level of the tetrapeptide by to be determined by enzyme immunoassay with good sensitivity and specificity. We present results demonstrating the presence of AcSDKP in humans: serum levels of 34 healthy controls were found to be between 0.7 and 2.5 pm/ml, regardless of age and sex. High levels were found in 44% of asymptomatic controls but only in 8% of AIDS patients out of a total of 37 patients with HIV. Subsequently, studies of serum levels were performed before treatment in 121 subjects with disorders of the nonlymphoid and the lymphoid lineages. Our results did not demonstrate any decrease in serum levels, however a moderate or marked increase was noted in one-third of the subjects, which was greater in disorders of the non-lymphoid lineages (48% of 72 patients) than the lymphoid lineage (21% of 50 patients). The most significant differences were observed between controls versus patients with myeloproliferative disorders (MPD, 24 patients: p < 0.001), controls versus patients with acute myelogenous leukaemia (AML, 15 patients: p < 0.02), as well as patients with AML versus patients with primary myelodysplastic syndromes (PMDS, 10 patients: p < 0.05). The pathophysiology of these abnormalities is discussed. PMID- 8501977 TI - Effects of H-7 and staurosporine on proliferation and self-renewal of acute myeloid leukemia progenitors. AB - In this study, we compared the impact of two protein kinase (PK) inhibitors, H-7 and staurosporine, on the normal myeloid progenitors (CFU-GM) and acute myeloid leukemia progenitors (AML-CFU) proliferation measured by in vitro clonogenic assay. H-7 and staurosporine displayed a biphasic dose-effect on both CFU-GM and AML-CFU recovery. At the lowest concentration range (0.1 microM to 20 microM for H-7 and 0.1 nM to 1 nM for staurosporine), we observed growth stimulation whereas higher concentrations induced dose-dependent growth inhibition. Moreover, AML-CFU proved to be significantly more sensitive to the inhibitory effect of both H-7 and staurosporine than CFU-GM (3.16- and 2.12-fold, respectively). These results were further confirmed with comparable murine cell line models (FDC-P1, a hematopoietic cell line generated from normal bone marrow and WEHI, a myelomonocytic leukemia cell line). Furthermore, we report that both H-7 and staurosporine present similar inhibitory effects on proliferation (PE1) as on self-renewal (PEs) of AML-CFU. In an attempt to understand more fully the mechanism of action of H-7 and staurosporine, we investigated their impact (when used at their D50) on the human myelogenous leukemia cell line, K562. H-7 and staurosporine induced a transient decrease of cell growth, between 0 and 24 hours, and produced a transient blockade of K562 cells in the S-phase, either 24 or 48 hours after the addition of staurosporine and H-7, respectively. PMID- 8501978 TI - Severe toxicity limits intensification of induction therapy for acute lymphoblastic leukemia. AB - Fourteen adult patients with newly-diagnosed acute lymphoblastic, leukemia (ALL), and lymphoblastic lymphoma, were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission, in an attempt to increase the fraction of patients who are long-term disease-free survivors. The induction regimen included vincristine, prednisone, intermediate-dose cytarabine (Ara-C), and idarubicin, all given during the first week of therapy. This combination led to significant hepatic, gastro-intestinal, infectious, and neurologic toxicity. There was unacceptable treatment-related mortality (29%). After the first eight patients, the study was modified, omitting the Ara-C from the induction phase. Gastrointestinal morbidity was less in the cohort treated without Ara-C; however, infectious morbidity persisted at unacceptable levels and this program was terminated as too toxic to administer. There were nine complete remissions, three early deaths, and two patients with resistant disease. There have been six relapses, three of which occurred in patients who, because of protracted grade III/IV toxicity, were no longer receiving chemotherapy. With a minimum follow-up of 20 months, only three patients are still alive. We conclude that this combination of vincristine, prednisone, Ara-C, and idarubicin, is too toxic to be used as induction therapy for adult patients with ALL and lymphoblastic lymphoma. PMID- 8501979 TI - Structural abnormalities of the X chromosome in non-Hodgkin's lymphoma. AB - It has recently been reported that additional X chromosomes occur in over 30% of B-cell non-Hodgkin's lymphomas (NHL), and that monosomy of the X chromosome occurs in 38% of female patients with T-cell leukaemia or lymphoma. These observations have suggested a possible role for the X chromosome in the evolution of NHL. We have now examined 280 cases of NHL, and have identified 19 examples of structurally altered X chromosomes in the malignant cells from 17 of these cases. These abnormalities were mainly characterized by either a translocation involving Xp22, or a translocation/deletion involving Xq28. The relevance of these observations is discussed with respect to other published reports, and together they suggest that lymphoma-associated oncogenes may exist on the X chromosome at bands p22 or q28. PMID- 8501980 TI - Tissue factor and plasminogen activator inhibitor expression in the differentiation of myeloid leukemic cells. AB - Disturbances in the regulation of the balance between the fibrinolytic and procoagulant properties of leukemic cells may contribute to the coagulopathy of acute leukemia. The coagulant response to a number of stimuli is regulated by the expression of tissue factor, but the role of the plasminogen activator inhibitors, PAI-1 and PAI-2, in contributing to the net coagulant response is not known. In this study, we have examined the production of these proteins by cultured myeloid leukemic cells arrested at different stages of differentiation. Northern blot analysis showed time-dependent and differential production of mRNA for PAI-2 and tissue factor, and to a much lesser extent, PAI-1, in response to the differentiating agent, 12-phorbol-13-myristate acetate. The capacity to synthesize PAI-2 appeared to be related to the stage of myeloid cell differentiation. Examination of the gene products by immunoblot analysis demonstrated multiple forms of PAI-2 in all myeloid cells examined. In addition, a common characteristic of all the myeloid cells was the production of a high molecular weight species of tissue factor which may be a secreted form unique to leukemic cells. Taken together, the findings demonstrate that myeloid leukemic cells are capable of generating a multicomponent coagulant response. PMID- 8501981 TI - Effect of doxorubicin, daunorubicin, and idarubicin on the growth rate of human leukemia cells (K562) studied with image analysis. AB - The effects of doxorubicin, daunorubicin, and idarubicin on the growth of K562 cells were investigated by monitoring the formation of individual colonies in semi-solid culture employing an automated image analysis system. Drug effects were evaluated using short-term exposure (2 h) at clinically achievable drug plasma concentrations. Following drug exposure, heterogeneity in growth patterns was observed which was categorized into three distinct types; (1) continuous growth at a decreased growth rate; (2) limited growth; (3) no growth. In addition to a concentration-dependent decrease of the growth fraction, a reduction of the growth rate of the continuously growing colonies was observed. At equitoxic drug concentrations, comparable changes in growth rate were observed for each of the three anthracyclines studied. It is demonstrated that the fraction of cells which escape drug-induced growth arrest with therapeutically achievable drug concentrations display a significant decrease in growth rate. PMID- 8501982 TI - Leukemic transformation of immortalized FDC-P1 cells engrafted in GM-CSF transgenic mice. AB - Injection of 10(6) immortalized, but non-leukemic, granulocyte-macrophage colony stimulating factor (GM-CSF)-dependent FDC-P1 cells into GM-CSF transgenic hybrid mice with elevated GM-CSF levels led to death within three months with elevated blast cell numbers in the blood, massive organ infiltration by blast cells, and associated anemia and thrombocytopenia. No disease developed within this period in littermate mice injected with 10(6) FDC-P1 cells. All moribund transgenic recipients contained transformed FDC-P1 cells able to produce rapidly-growing transplanted leukemias in syngeneic normal DBA/2 recipients. The leukemias appeared to arise in the primary recipients by independent transformation events. The transformed cells from different mice differed in their in vitro growth characteristics, their ability to produce GM-CSF or multipotential CSF, and in the nature of the transplanted tumors derived from the primary cells. While all primary recipients at death contained fully transformed leukemic cells, the bulk of the large population of FDC-P1 cells appeared either to be untransformed or to have altered characteristics not yet representing full transformation. If the FDC P1 engrafted model has some validity for myelodysplasia, the results suggest that sustained CSF administration to myelodysplastic patients possessing abnormal, potentially preleukemic, granulocyte-macrophage populations may increase the risk of death either from accumulated pretransformed or from fully transformed leukemic cells. PMID- 8501984 TI - T-cell form of chronic lymphocytic leukaemia. PMID- 8501983 TI - Cell populations during tumorigenesis in Eu-myc transgenic mice. AB - Transgenic mice bearing a c-myc oncogene under control of the immunoglobulin heavy chain (Igh) enhancer (Eu-myc mice) (1, reviewed in 2) undergo a reproducible series of developmental stages and die from malignancies of the B lymphocyte lineage. To investigate the cellular events underlying tumorigenesis in this model, we quantified B lymphoid subpopulations and turnover at various stages of this process. An early stage was characterized by the presence in the blood of many large proliferating B lineage cells marked by surface antigen phenotype IgM+l-, B220low, CD5-, Mac-1low. During a prolonged intermediate 'remission' phase of different duration in each mouse, B lymphocytes in the periphery were non-proliferative, few, and of conventional phenotype (IgM+, B220+, CD5-, Mac-1-), while subsets of precursor B cells were both numerous and highly proliferative in the bone marrow. In the final stage of tumorigenesis, large proliferating cells similar in phenotype to those of the early period reappeared and increased rapidly in numbers. This B cell tumorigenic progression occurred independently of interactions with T lymphocytes. Evidence of massive cell death in the bone marrow during the intermediate phase, plus molecular characterization of the final tumors, suggested that the end of the peripheral 'remission' period and entry into the terminal stage of tumorigenesis may be due to a clone of cells acquiring the ability to circumvent normal processes of cell death and elimination that usually regulate the egress of B cells from the bone marrow to the periphery. PMID- 8501985 TI - CLL should be used only for the disease with B-cell phenotype. PMID- 8501986 TI - Lineage commitment in biphenotypic acute leukemia. AB - Acute leukemias (ALs) with phenotypic and genotypic features of several hematopoietic lineages are difficult to classify and may represent the transformation of multipotent stem cells. We have studied immunological features of 200 cases of acute leukemia (109 acute myelogenous leukemia, AML, and 91 acute lymphoblastic leukemia, ALL, according to FAB criteria), including 17 (8.5%) classified as biphenotypic by a scoring system based on the number and specificity of unexpected lineage antigens and which gives more weight to cytoplasmic markers such as myeloperoxidase, CD3, and CD22, and less to other membrane markers. Sixty-eight AML and 42 ALL cases were also examined for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) beta, gamma, and delta genes, and these included 12 biphenotypic AL. The expression of myeloid antigens in ALL was seen in 25% of the cases. All B-lineage ALL had rearrangements and/or deletions of the Ig genes whereas TCR beta, gamma, and delta genes were rearranged in 21%, 52%, and 71%, respectively. TCR delta, gamma and/or beta were rearranged in T-ALL and four out of 13 cases had Ig gene rearrangement. Lymphoid-associated antigens were expressed in 40% of AML cases; those most frequent expressed were CD7 (17%), CD2 (15%), CD19 (10%), and CD10 (7.5%). Evidence of Ig and/or TCR gene rearrangements was detected in 12% of AML cases. There was no correlation between the isolated expression of terminal deoxynucleotidyl transferase (TdT), B, and T-cell antigens with Ig and TCR gene rearrangements. However, in cases of AML defined as biphenotypic because they expressed two or more lymphoid antigens there was a statistically significant correlation between gene rearrangements and lymphoid score (p < 0.001). Our findings support the concept of biphenotypic leukemia as a distinct entity in which there is frequent correspondence between phenotypic and genotypic changes. PMID- 8501988 TI - An evaluation of generic screens for poor quality of hospital care on a general medicine service. AB - In this study, 675 general medicine admissions at a university teaching hospital were reviewed to evaluate six potential generic quality screens: 1) in-hospital death; 2) 28-day early readmission; 3) low patient satisfaction; 4) worsening severity of illness (as determined by an increase in Laboratory Acute Physiology and Chronic Health Evaluation APACHE-L); and 5) deviations from expected hospital length of stay; and 6) expected ancillary resource use. The quality of care for a stratified random sample of admissions were evaluated using structured implicit review (inter-rate reliability, Kappa = 0.5). Patients who died in-hospital were substantially more likely than those who were discharged alive to be rated as having had substandard care (30% vs. 10%; P < 0.001). In contrast, cases who had subsequent early readmissions did not have poorer quality ratings. Similarly, lower patient satisfaction was not associated with poorer ratings of technical process of care. Cases with lower-than-expected ancillary resource use (case-mix adjusted for diagnosis-related group) were more likely to be rated as having received substandard care than those with higher-than-expected resource use (16% vs. 6%; P < 0.05), and there was a similar trend for cases with shorter than expected length of stays. Associations between worsening severity of illness, as determined by APACHE-L scores, and quality were confounded because such patients were more likely to have died in-hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8501987 TI - The effects of unit self-management on hospital nurses' work process, work satisfaction, and retention. AB - A number of innovative practice models have been introduced in an effort to resolve the hospital nursing shortage and improve the working conditions and retention of registered nurses. This study examines the effects of a unit-level self-management model (including salaried compensation and gainsharing) in a number of clinical areas at The Johns Hopkins Hospital in Baltimore, Maryland. In comparisons of nurses on self-managed and traditional nursing units, outcomes examined were nurses' perceptions of their work process, nurses' work satisfaction levels, and nurses' retention. The self-management model is found to increase work satisfaction through effects on two work process variables: coordination of care and effective team performance. The model is also associated with higher retention. Nurses on self-managed units work longer hours but earn increased pay; the effects of hours and pay on work satisfaction and retention are discussed. PMID- 8501989 TI - Discounting in the economic evaluation of health care interventions. AB - Do economic theories that underlie discounting have specific implications for program evaluation in health? In this study, both the contemporary practice and the theoretical foundations of discounting are reviewed. The social discount rate controversy is considered, and the two major concepts (i.e., opportunity cost and time preference) involved in the formulation of a social discount rate are outlined. Also described are the arguments for discounting proposed by thinkers in non-economic disciplines. Finally, the implications of choosing a discount rate for evaluation of individual health care programs are considered. It is argued that the conventional practice of discounting all health care programs at a rate of 5% may not consistently reflect societal or individual preference. Specific recommendations arising from this paper are: 1) given the considerable disagreement at the theoretical level as to the appropriate social discount rate, analysts should be specific about what theoretical approach underlies their choice of rate, especially when the analytic result is sensitive to the discount rate; 2) the discount rate chosen should be appropriate for the perspective of the analysis (social vs. individual vs. institutional, etc.); 3) when appropriate, measures should be taken to avoid double discounting, because some health related outcome measures already incorporate individuals' time preference; and 4) it is suggested that the political process may serve as the appropriate means of reflecting social values in the choice of a discount rate. In addition, the authors argue that a consensus conference approach, with political participation, offers a flexible, pragmatic, and explicit way of synthesizing the empirical, normative, and ethical considerations that underlie choice of a discount rate. PMID- 8501990 TI - Predicting psychosocial risk in patients with breast cancer. AB - Breast cancer is the most common neoplasm in North American women. The psychosocial impact of breast cancer has been extensively studied, and a number of investigators have attempted to characterize women who are at high risk for increased psychosocial morbidity. Although a detailed interview performed by a professional is the clinical standard for psychosocial assessment, such interviews are usually time-consuming and expensive, and thus are rarely performed. This study was designed to develop a strategy for the rapid identification of newly-diagnosed breast cancer patients at risk for psychosocial morbidity. A sample of 227 newly diagnosed breast cancer patients were interviewed systematically by a clinical social worker and were subsequently classified for risk of psychosocial distress in the year after diagnosis. In addition, these women completed a battery of standardized instruments designed to assess quality of life, rehabilitation needs and psychological distress. A logistic regression procedure was used to examine a wide range of variables for their ability to correctly classify the risk of psychosocial distress in this sample. The final model included the Cancer Rehabilitation Evaluation System (CARES) Psychosocial Summary Scale, the Karnofsky Performance Status score and age as the best predictors of psychosocial risk. Subsequently these three variables were used to construct a clinically usable risk prediction model. Additional research should be performed to validate this predictive model. PMID- 8501991 TI - Multiuse of medicines in Finland. AB - The purpose of this study was to investigate the occurrence of multiuse of prescription drugs and its major determinants among Finnish adults. The data were based on three nationally representative and intercomparable health surveys in 1976, 1978-80, and 1987. The study populations were 16,413 in 1976, 13,138 in 1987, and 7,217 in 1978-80. The simultaneous use of at least five prescription drugs was the main outcome measure. In 1976, 4.7% of the study population, and 6.3% in 1987 were multiusers. Of all users of prescription drugs, the proportion of multiusers was 14% both in 1976 and 1987. In 1987, the elderly comprised 55% of all multiusers, whereas their share in 1976 was 44%. The strongest predictor of the multiuse was, as expected, chronic morbidity. Of the various diagnostic groups, the main determinants were cardiac insufficiency, hypertension, asthma, mental disorders, and coronary heart disease. Even allowing for chronic morbidity, age was significantly associated with multiuse, but sex was not. The number of visits to a primary care physician correlated also independently with the multiuse. These findings indicate that the elderly may in part get prescriptions indiscriminately. PMID- 8501992 TI - Effects of an education program for community pharmacists on detecting drug related problems in elderly patients. AB - Community pharmacists are in a position to assume increased responsibility for preventing and resolving drug-related problems in ambulatory patients. Such an expanded role is mandated under provisions of the Omnibus Budget Reconciliation Act of 1990. The need for pharmacist oversight of drug therapy may be most acute in elderly patients. This study reports on a program to teach community pharmacists a process of assessing drug therapy of elderly patients and intervening to correct problems. Community pharmacists (N = 102) were assigned to treatment and control conditions. Both groups targeted patients meeting criteria and enrolled them into the study. Treatment group pharmacists, who participated in a training program, also assessed the medication use of enrolled patients to identify and resolve medication-related problems. Patients (N = 762) were telephoned by researchers 1 month after enrollment for an interview. Comparisons between treatment and control group patients were made on reports of pharmacist activities, knowledge of regimens, compliance, and potential drug therapy problems, such as interactions and side effects. Treatment patients were more likely to report that pharmacists provided information and assessed for problems than were control patients. These differences were maintained on 3-month follow up questionnaires. No differences were found on the odds that patients indicated misunderstanding of regimens, non-compliance, or potential therapeutic problems. PMID- 8501993 TI - Data about mortality. PMID- 8501994 TI - Effects of military experience on mental health problems and work behavior. PMID- 8501995 TI - Variations in the outcomes of care provided in Pennsylvania nursing homes. Facility and environmental correlates. AB - This research study utilizes indicators from federal and state surveys to evaluate variation in outcomes in 438 Medicare certified skilled nursing care facilities in Pennsylvania. First, a standardization function adjusting for patient characteristics known to influence outcomes was developed and estimated. The relationships between organizational and environmental characteristics and the chosen outcome indicators (i.e., differences between the actual and expected rate of mortality, pressure ulcers, urethral catheterization and physical restraints) were then analyzed by weighted least squares regression. Results suggest considerable interfacility variation in rates for these outcome indicators. A portion of this variation is significantly attributable to resident characteristics (P < or = 0.05). However, variation in outcomes in Pennsylvania facilities is also associated with facility characteristics (e.g., size and for profit status), and environmental characteristics (e.g., per capita income and bed supply). Implications for nursing home management and policy are considered. PMID- 8501996 TI - The impact of cancer screening promotion by rural hospitals on cancer detection. AB - Hospitals almost universally provide health promotion programs for community residents. There is a lack of evidence regarding these programs' impact on the detection or prevention of disease. The purpose of the present study was to determine whether rural hospital-based health promotion programs for cancer screening were associated with detection of greater numbers of cancer cases in the communities served by the hospitals over the years that the promotion programs were offered. Data were collected from a survey of 95 rural Iowa hospitals and from state health registry data on 1985-1990 cancer occurrence. Breast and colon cancer screening promotion programs were related to detection of greater numbers of cases, after controlling for population, age and sex. These findings often held for both less advanced and more advanced cancer stages. Promotion of cervical cancer screening was not related to number of cervical cancers detected. The finding that the relationship between screening promotion and cancer detection persists irrespective of stage may have important policy and programmatic implications. PMID- 8501997 TI - Using claims data for epidemiologic research. The concordance of claims-based criteria with the medical record and patient survey for identifying a hypertensive population. AB - In this study, a method was developed to identify health plan members with hypertension from insurance claims, using medical records and a patient survey for validation. A sample of 2,079 patients from two study sites with medical service or pharmacy claims indicating a diagnosis of essential hypertension were surveyed, and the medical records of 182 of the 1,275 survey respondents were reviewed. Where the criteria to identify hypertensive patients used both the medical and pharmacy claims, there was 96% agreement with either the medical record or the patient survey. Where the criteria relied on medical claims alone, the agreement rate decreased to 74% with the medical record and 64% with the patient survey. Where the criteria relied on the pharmacy claims alone, the agreement rate was 67% with the medical record and 75% with the patient survey. Combined evidence from medical service and pharmacy claims yielded a high level of agreement with alternative, more costly sources of data in identifying patients with essential hypertension. As it is more thoroughly investigated, claims data should become a more widely accepted resource for epidemiologic research. PMID- 8501999 TI - Rating journals in health care administration. The use of bibliometric measures. PMID- 8501998 TI - Adherence to continuous screening for colorectal neoplasia. AB - Continuous screening is defined as the periodic provision of an opportunity for diagnostic testing to a population of individuals who are asymptomatic and at increased risk for disease. If screening is offered periodically irrespective of response to an earlier screening invitation, this situation may be referred to as serial screening. When continuous screening is made available only to individuals who had tested previously, population member response is referred to as repeat screening. This study assessed adherence to serial- and repeat-colorectal cancer screening among older adult members of an independent practice association-type health maintenance organization (HMO) in two consecutive rounds of screening. In the first screening round, fecal occult blood tests (FOBTs) were sent to 1,565 subjects who were randomly assigned to receive usual care or behavioral interventions intended to encourage testing. Overall, 647 (41%) subjects completed and returned their tests. In the second screening round, FOBTs were mailed again to all subjects; however, the interventions were discontinued. Logistic regression analysis results shows that first-round testing was a significant independent predictor of serial adherence for subjects older than 65 years of age (odds ratio[OR] = 10.8) and those younger than 65 years of age (OR = 10.9); and a significant negative association between exposure to first-round intervention and serial adherence (OR = 0.5) was found among younger subjects. Among first-round adherers, age was significantly and positively related to repeat adherence (OR = 1.6). However, exposure to first-round intervention and having an abnormal FOBT result were significantly and negatively associated with repeat adherence (OR = 0.5 and OR = 0.4, respectively). The results of this study reported here indicate that previous screening is a strong predictor of serial adherence, and special efforts may be required to achieve high levels of serial and repeat adherence among younger adults. Additional research is needed to understand why persons with abnormal screening test results are unlikely to engage in repeat screening. PMID- 8502000 TI - Evaluating hospital performance with case-mix-adjusted outputs. AB - In this article, we compared hospital efficiency using a multiple input-output approach in two ways: one way used a straightforward count of inpatient days and outpatient services as outputs; and the second used a case mix-adjusted count of inpatient services and outpatient care as outputs. Our results show that there was no difference when we incorporated the case-mix index, either as a weighting device or as a separate output. However, this result may be due to our having a relatively homogeneous sample, (i.e., large metropolitan hospitals). Variations using this approach may occur when using a more heterogeneous sample, such as comparing hospitals of all sizes or rural versus urban hospitals. PMID- 8502001 TI - Specialty changes made by young physicians from graduate training to practice. PMID- 8502002 TI - Performance, characteristics, and case mix in Japanese and American teaching hospitals. PMID- 8502003 TI - Improving choice of prescribed antibiotics through concurrent reminders in an educational order form. PMID- 8502005 TI - [Clinton's health care reform: necessary, expensive, criticized]. PMID- 8502004 TI - Trends in the prescription of psychotropic medications. The role of physician specialty. PMID- 8502006 TI - [Are internship positions threatened?]. PMID- 8502007 TI - [Is it possible to understand the misunderstandings in vascular surgery?]. PMID- 8502008 TI - [Arthritis is toned down in adult-onset Still's disease]. PMID- 8502009 TI - [Time to react against journalistic speculation]. PMID- 8502010 TI - [Discrepancies in the statistics of HIV-positive persons should be corrected]. PMID- 8502011 TI - [Recommended treatment for impotence]. PMID- 8502012 TI - [Occupational injury compensation and justice]. PMID- 8502013 TI - [Should the proposal for reform of family practice include free service?]. PMID- 8502014 TI - [Microdialysis. A unique method for measurements in different tissues of interest for metabolic research]. PMID- 8502015 TI - [A test for direct microbiological diagnosis in the patient. Evaluation and use]. PMID- 8502016 TI - [HIV screening of pregnant women and blood donors]. PMID- 8502018 TI - [Patient dying after streptococcal septicemia. She developed mycotic aortic aneurysm]. PMID- 8502017 TI - [Handicap can be traced by a simple self test. A new screening instrument for population studies]. PMID- 8502019 TI - [Environmental pollution results in morbidity. Physicians' silence is alibi for passivity]. PMID- 8502020 TI - [Case report. A cure against giant intracranial aneurysm]. PMID- 8502021 TI - [New methods should be evaluated before they are widely used]. PMID- 8502023 TI - [The doctoral candidate's work and knowledge measurement. Much debated elements in postgraduate studies]. PMID- 8502022 TI - [Laparoscopic surgery is not a new discovery. Tips about prevention of adverse effects already exist]. PMID- 8502025 TI - [Only the teachers are in favour for grades]. PMID- 8502024 TI - [The Remmelink report is not the only source. Cryptothanasia in the Netherlands- sufficiently documented]. PMID- 8502026 TI - [Long travels should be avoided during late pregnancy]. PMID- 8502027 TI - [The professor should also act as chief physician]. PMID- 8502028 TI - [Huntington's disease. The elusive "gene" is now identified]. PMID- 8502029 TI - [Chernobyl 7 years after the disaster. Increased number of thyroid cancer]. PMID- 8502030 TI - [Treatment with cytostatic agents. Changed practice, thanks to cancer research- not as a consequence of a consensus statement]. PMID- 8502031 TI - [Gaucher disease is treatable. Good results with a new form of enzyme substitution]. PMID- 8502032 TI - [2 cases of severe hemorrhage. Serious injuries in laparoscopic surgery]. PMID- 8502033 TI - [The good death and health care. A contribution to the impossible debate on euthanasia]. PMID- 8502034 TI - [2 unusual cases of uterine rupture. A common labor complication in developing countries]. PMID- 8502035 TI - [Clostridium difficile enteritis complicated by symphysitis. Good effect of fecal streptococci]. PMID- 8502036 TI - [Superselective catheterization. Treatment of sinus thrombosis directly in the thrombi]. PMID- 8502037 TI - [A case report. Psychotic symptoms in a patient with HIV-1 infection]. PMID- 8502038 TI - [Need for evaluation in psychiatry. Mental disorders cost 45 billions per year]. PMID- 8502040 TI - [The golden age of radiology is here. But is there enough gold?]. PMID- 8502041 TI - [Why does the geriatric reform give different compensation to discharged patients?]. PMID- 8502039 TI - [Lorenzo's oil. A realistic presentation of two parents' fight against adrenoleukodystrophy]. PMID- 8502042 TI - [Let the active listing grow without haste]. PMID- 8502043 TI - [A clause of conscience against abortion for students?]. PMID- 8502044 TI - [Field hospital--for whom?]. PMID- 8502045 TI - [Do electromagnetic fields or chemicals cause cancer?]. PMID- 8502046 TI - [Alzheimer's disease. Computer tomography--a good diagnostic method?]. PMID- 8502047 TI - [Hemoconcentration via ANP in pre-eclampsia. A recently discovered peptide antagonist to the RAA system]. PMID- 8502048 TI - [Psychopharmaceuticals and persons seeking asylum. Low prescription rate in refugee camps]. PMID- 8502049 TI - [Surgical glove powder--an overlooked risk. Severe adverse effects are well documented]. PMID- 8502050 TI - [Ventilation systems for operating rooms. More bacteria in the compressed air system]. PMID- 8502051 TI - [Encephalocele with cerebrospinal fistula. An unusual case with life-threatening complications]. PMID- 8502052 TI - [Case report. Electric accident at an ICU]. PMID- 8502053 TI - [Case reports. 2 techniques for emergency coniotomy]. PMID- 8502054 TI - [A pregnant black woman received several wrong diagnoses. Sickle cell disease turned out to be the cause of pain]. PMID- 8502055 TI - [Inquiry on smoking cessation. Smokeless zones support smoking cessation]. PMID- 8502056 TI - [Are the fetuses of brain dead women to be saved?]. PMID- 8502057 TI - [The new debate on brain death is a storm in cup of water]. PMID- 8502058 TI - [Don't let competition destroy competence. Are clinical laboratories at risk?]. PMID- 8502059 TI - [Explicit communication is desirable in psychoanalysis]. PMID- 8502060 TI - [Joint Scandinavian follow-up is valuable for lumbosacral rhizotomy]. PMID- 8502061 TI - [Preparedness against scientific fraud]. PMID- 8502062 TI - [Stroke. Changing treatment]. PMID- 8502063 TI - [Computer-assisted ECG interpretation. How can the new technique be used in health care?]. PMID- 8502064 TI - [Functional dyspepsia. A complaint difficult to treat, demanding individual therapy and active cooperation with the patient]. PMID- 8502065 TI - [Mechanisms and syndromes in stroke. Prognosis and therapeutic effects are dependent on the cause]. PMID- 8502066 TI - [Stroke released the creative force]. PMID- 8502067 TI - [Suppression of bone marrow after drug interaction]. PMID- 8502068 TI - [Why does it happen just to me? Parents' experiences with difficult questions from children with functional disabilities]. PMID- 8502069 TI - [Thoracoscopic surgery. A new alternative in thoracic surgery]. PMID- 8502070 TI - [Glue treatment. A biological double-component glue can replace thoracic surgery]. PMID- 8502071 TI - [Cost effectiveness of British ambulatory surgery. A minimum of personnel provides high quality care]]. PMID- 8502072 TI - [Hans Wigzell about stress and susceptibility to infections. Modern myths are based on wrong sources. Interview by Birgit Wilhelmson]. PMID- 8502073 TI - [Accidental hypothermia. 2 case reports]. PMID- 8502074 TI - [Diffuse pulmonary or cerebral metastases in young women. Pregnancy tests should be included in the examination]. PMID- 8502075 TI - [The importance of compensating for the declining functions in the elderly. Better lighting increases the quality of life]. PMID- 8502076 TI - [Is there a risk of legalization of active euthanasia? Discussion on chronic vegetative conditions is important]. PMID- 8502077 TI - [The abortion rules are liberal also for women from foreign countries. The Judicial Committee grants most of the applications]. PMID- 8502078 TI - [Penny-wise and pound-foolish? Neurosurgery is needed for care of cranial injuries]. PMID- 8502079 TI - [Developing ESWL in Sweden has its advantages]. PMID- 8502080 TI - [Cooperation is A and O for field hospitals]. PMID- 8502081 TI - [The parallelism defense/care?]. PMID- 8502082 TI - [Treatment of bleeding esophageal varices. Endoscopy, interventional radiology or surgery?]. PMID- 8502083 TI - [A follow-up study of children of alcoholic mothers. What happened to the alcohol damaged children?]. PMID- 8502084 TI - [Central dialysis catheters. Lower frequency of septicemia with improved routines]. PMID- 8502086 TI - [Time to put limits on prenatal diagnosis]. PMID- 8502085 TI - [Offer hepatitis B vaccination to the addicts. Transmission of hepatitis B among intravenous drug abusers]. AB - Structured interviews with 75 intravenous drug abusers (IVDAs) in Stockholm showed that, despite their having had several contacts with various medical institutions or prisons, none had been offered vaccination against hepatitis B virus (HBV) infection as recommended by the National Board of Health and Welfare. We conclude that, as failure to offer HBV vaccination to IVDAs contributes to be continued spread of HBV infection in this category, at admission all IVDAs should undergo serological HBV-testing and vaccination be offered to HBV-negatives. PMID- 8502087 TI - [Prenatal diagnosis--ethical aspects. Guidelines from the Ethics Committee of the Medical Society]. PMID- 8502088 TI - [Smokeless health care only with the help of law. Efforts done by the county councils are good but insufficient]. PMID- 8502089 TI - [Treatment after myocardial infarction. Is rapid administration of t-PA + heparin most effective?]. PMID- 8502090 TI - Polymerase chain reaction amplification of DNA from archival celloidin-embedded human temporal bone sections. AB - A method was developed for fast and efficient isolation of DNA from formalin fixed, decalcified, celloidin-embedded human temporal bone sections for subsequent use in polymerase chain reaction (PCR) DNA amplification. The method relies on the use of an enzymatic digestion with proteinase K to release and solubilize the patient's DNA from an individual 20- to 25-microns temporal bone section. The method described should be of great value to those investigators extracting DNA from archival individual human temporal bone sections for polymerase chain reaction assays of specific genetic alterations associated with temporal bone pathologies. The molecular characterization of viral infections, oncogenes, or other etiological agents of disease using PCR could provide important information regarding the etiopathogenesis of many auditory, vestibular, and facial nerve disorders, such as autoimmune hearing loss, congenital hearing losses, Meniere's disease, otosclerosis, or Bell's palsy. PMID- 8502091 TI - Sensorineural hearing loss associated with aortocoronary bypass surgery: a prospective analysis. AB - A prospective, clinical study was undertaken to assess the relationship between aortocoronary bypass surgery (ACBS) and sensorineural hearing loss (SNHL). Between August 1, 1988 and July 31, 1989, 1458 patients underwent ACBS and 181 volunteers were entered into the study based on availability and capability to complete preoperative and postoperative questionnaires and audiometric testing. One hundred forty-five patients completed the study. Intraoperative audiant brainstem response (ABR) testing was performed on 7 patients with essentially normal hearing. Although 4 patients (2.8%) reported a subjective change in hearing on postoperative questionnaires, objective testing did not confirm a significant hearing change in pure-tone, speech discrimination, or speech reception threshold testing. Acute or sudden SNHL within 2 weeks following ACBS was not identified in any patient completing the study. This study did not provide evidence to support a causal relationship between SNHL and ACBS. However, if SNHL does occur following ACBS, the well-established etiology of ototoxic therapy and subsequent SNHL demands exclusion in the absence of conflicting histopathologic information. PMID- 8502093 TI - Role of hyperbaric oxygen therapy in the management of mandibular osteoradionecrosis. AB - Hyperbaric oxygen (HBO) has been used as a tool in the management of osteoradionecrosis (ORN). However, it has not been conclusively proven to be of benefit. The precise role and guidelines for its use also have not been clearly defined. This report retrospectively analyzes 41 patients treated at the Hyperbaric Chamber Unit at the Toronto Hospital (Toronto General Division) with proven mandibular ORN from 1980 to 1985. The results show that 83% of the patients had a significant improvement with HBO therapy, judged by at least a 50% decrease in the size of the exposed bone, closing of the fistulous tract, or complete relief of symptoms. Within the group of patients who were significantly improved, 15% showed complete resolution of ORN. Seven (17%) of the patients did not benefit from the HBO. All seven patients had radiological evidence of dead bone. Based on these observations, the following conclusions can be made: 1. HBO is of benefit in the management of ORN. 2. Patients with ORN may be divided into two groups: mild and severe. 3. Cases of mild ORN will heal with HBO alone, but, in severe ORN, surgery is necessary to remove dead bone. 4. All patients with ORN should receive dental evaluation, local wound care, and a strict oral hygiene regimen. Diseased teeth should be removed prior to radiotherapy. Subsequently, any teeth that became abscessed should be extracted in conjunction with prophylactic HBO. Antibiotics play an ancillary role in the management of ORN. For patients who have received radiation to the mandible, the authors propose regular follow-up in order to detect ORN at a time when HBO can arrest the disease. PMID- 8502092 TI - Salicylate-induced changes in cat auditory nerve activity. AB - The purpose of this study was to measure, in the cat, spontaneous auditory nerve (AN) activity before and after injection with sodium salicylate. Ten cats were anesthetized, and the AN and round window (RW) were surgically exposed. Electrodes were applied to allow recording from three channels, including bipolar electrodes and monopolar electrodes located directly on the auditory nerve, in addition to an RW electrode. Spectral averaging of the spontaneous activity was performed before and during salicylate treatment. An increase in spectral activity near 200 Hz was noted in all cats by 3 hours after salicylate injection. This activity was present in bipolar, monopolar, and RW records, and was temporarily diminished or eliminated by injection of lidocaine. No such spectral changes were found in saline-injected control animals. These results show promise of developing a noninvasive, objective, quantitative measure of tinnitus for studies in animals and in man. PMID- 8502094 TI - Cartilage tympanoplasty for management of retraction pockets and cholesteatomas. AB - Retraction pockets of the tympanic membrane, often associated with dysfunction of the eustachian tube, can be destructive, leading to loss of hearing, ossicular erosion, and development of cholesteatomas. This retrospective study reviews results from 35 patients (38 ears) operated on from January 1988 to June 1991 whose composite cartilage-perichondrial grafts harvested from the tragus were used to reconstruct the tympanic membrane. Early grafts reinforcing the posterosuperior quadrant of the pars tensa showed some failures, with recurrent retraction in the attic. In later grafts, additional placing of cartilage under the pars flaccida prevented failures in the attic. Our indications, initial technique and refinements to the present form, and hearing results are discussed. PMID- 8502095 TI - Comparison of two methods of tonsillectomy. AB - No consensus exists regarding the best method of tonsillectomy. This report concerns two popular methods: 1. electrocautery excision and 2. dissection/snare followed by point coagulation of bleeding sites. To compare these methods, a prospective, randomized, single-blinded study was conducted in which 28 patients had one tonsil removed by dissection/snare and selective cautery of bleeders and the other removed by the electrocautery. Operative time and blood loss were compared. Patients rated the severity of their pain and blood loss postoperatively. Intraoperative bleeding was significantly less on the side of cautery excision, although the operative time was longer. At follow-up, pain was rated worse on the side of cautery excision. PMID- 8502096 TI - Cholinergic agents in the laryngeal chemoreflex model of sudden infant death syndrome. AB - The laryngeal chemoreflex results in apnea, laryngospasm, and cardiovascular changes that can be fatal when a liquid stimulus is placed on the laryngeal mucosa of infant mammals. This study of 35 piglets assessed the effects of the cholinergic agents atropine and edrophonium on this laryngeal reflex response. Atropine, when placed intrathecally, resulted in a significant reduction of apnea as well as a decrease in the cardiovascular changes that occur during the reflex 60 minutes following its injection. Edrophonium, when placed intrathecally, resulted in a significant prolongation of apnea as well as death by asystole in 2 animals during laryngeal stimulation. Atropine placed intravenously also resulted in a significant reduction of apnea length, but required greater than 180 minutes to do so. PMID- 8502097 TI - Use of the holmium: yttrium aluminum garnet (Ho:YAG) laser for cranial nerve decompression: an in vivo study using the rabbit model. AB - A study was designed to evaluate the utility and safety of the holmium:yttrium aluminum garnet (Ho:YAG) laser for precise bony decompression of neural canals. In vivo rabbit studies were performed to measure temperature changes and nerve degeneration which occurred when the facial canal was decompressed with the laser as compared to the diamond burr. Marked temperature elevations were noted with the laser (n = 4), but not with the burr (n = 4). Seven of nine nerves decompressed with the laser revealed moderate to severe degeneration, whereas two control nerves decompressed with the drill demonstrated only minimal degeneration. It is concluded that this laser should not be used for nerve decompression unless better control of temperature elevation can be achieved. PMID- 8502098 TI - Passy-Muir tracheostomy speaking valve on ventilator-dependent patients. AB - Communication for handicapped ventilator-dependent patients is a problem, not only for the patient but also for the healthcare personnel. The inability of these patients to vocalize is a paramount problem in their care. This study evaluates the efficacy of a one-way speaking valve on ventilator-dependent patients and evaluates the resulting effectiveness of their speech. Fifteen ventilator-dependent patients were fitted with the one-way Passy-Muir Tracheostomy Speaking Valve and their communicative skills and ease of vocalization were evaluated. This clinical evaluation was done by the patient, a speech pathologist, two nurses in charge of the patient, and the patient's private physician. No complications were observed in any of the patients. All 15 patients showed marked improvement, not only in speech intelligibility but in speech flow, the elimination of speech hesitancy, and speech time. This ability to communicate enhanced the care given by the healthcare personnel. In conclusion, use of the Passy-Muir Tracheostomy Speaking Valve restored verbal communicative skills of ventilator-dependent patients, facilitated care, and greatly enhanced the mental outlook of these patients without observed complications. PMID- 8502099 TI - Tympanostomy tubes: experience with removal. AB - Whereas the clinical indications for tympanostomy tube placement are well established, the indications for operative tympanostomy tube removal remain unspecified. A 1-year retrospective review done at the Massachusetts Eye and Ear Infirmary revealed 131 tympanostomy tubes to have been removed under general anesthesia. Chronic otorrhea, granuloma formation, tube nonfunction due to blockage, and migration of the tube into the middle ear constituted the surgical indications in 75 cases. The remaining 56 tubes were removed on the physicians' judgment that artificial ventilation was no longer required. Selected cases are presented. While the vast majority of tubes spontaneously extrude uneventfully, a comparatively small number of patients do require operative tube removal. Practice guidelines for surgical tube removal are suggested. PMID- 8502100 TI - Role of radiation therapy in the management of carcinoma in situ of the larynx. AB - Twenty-one patients with carcinoma in situ of the larynx were treated with definitive irradiation from 1959 to 1987. The in situ changes were limited to 1 vocal cord in 19 patients, and to both vocal cords in 1 patient. One patient demonstrated extensive in situ changes involving the vocal cords bilaterally, as well as the anterior commissure, with both supraglottic and infraglottic extension. The mean follow-up from completion of treatment was 6.2 years, with a median of 50 months. Definitive irradiation resulted in a local control rate of 95%. The patient with extraglottic spread of in situ changes experienced a local failure 7 months after completion of treatment and, despite surgical salvage, died of local recurrence. This patient represents the only recurrence in our series. Our data suggest that radiation therapy can provide excellent control in carcinoma in situ limited to the true vocal cord. PMID- 8502101 TI - Manipulating the mobile stapes during tympanoplasty: the risk of stapedial luxation. AB - Manipulating the mobile stapes is a central procedure during tympanoplasty, i.e., mounting a prosthesis onto the stapedial head or dissecting cholesteatoma matrix off the oval window niche. An excessive displacement of the stapedial suprastructure as caused by these manipulations with hand-held instruments might result in a rupture of the annular ligament. Bacteria invading through this perilymphatic fistula threaten the inner ear. In experiments with temporal bones, the author investigated the rupture mechanisms of the annular ligament with definite stapedial manipulations. Leaks, which became detectable by exerting pressure on the inner ear fluid, occur only when all suspension fibers are completely ruptured. Further clinical aspects with different directions of stapedial manipulations are demonstrated. PMID- 8502102 TI - Computed tomography, magnetic resonance imaging, and electromyographic studies of tensor veli palatini muscles in patients with nasopharyngeal carcinoma. AB - One of the factors that induces eustachian tube dysfunction caused by the invasion of nasopharyngeal carcinoma is paralysis of the tensor veli palatini muscle. Electromyography (EMG), computed tomography (CT), and/or magnetic resonance imaging (MRI) were used to study the tensor muscle and the related paratubal structures and parapharyngeal space. This study, from 44 patients with nasopharyngeal carcinoma, showed that 67% of tensor muscles on the side of the symptomatic ear yielded abnormal electromyographic waveforms, which usually indicated a neurogenic disorder. In the majority of the abnormal EMG cases, CT or MRI often revealed that the pharyngobasilar fascia and the tensor muscle were compressed anterolaterally and the upper prestyloid parapharyngeal space was infiltrated. It was found that an abnormal electromyogram of the tensor muscle generally suggested a more advanced T stage and eustachian tube dysfunction. Otitis media with effusion in the stage I cases was usually not caused by paralysis of the tensor muscle. The invasion of some early cancers, especially localized on the torus tubarius, could also cause the effusion. PMID- 8502103 TI - Controlling the caloric labyrinthine stimulus: restoring surface temperature. AB - The duration of the conventional caloric stimulus is too long and the termination of the stimulus is uncontrolled. This study explores the use of a brief terminal "washout" irrigation pulse at 37 degrees C which is intended to 1. shorten the duration of action of the caloric stimulus and 2. eliminate uncertainty over the magnitude and duration of the terminal portion of the thermal labyrinthine stimulus. Twelve normal subjects were tested with 1. conventional 30-second irrigations, 2. 30-second irrigations plus a "washout" pulse, and 3. temperature switching caloric (TSC) irrigations plus a "washout" pulse. Clinical test scores were comparable with all three irrigation methods. The "washout" pulse produced only a slight shortening of the conventional 30-second irrigation responses. PMID- 8502104 TI - Botulinum toxin injection for adductor spastic dysphonia: patient self-ratings of voice and phonatory effort after three successive injections. AB - Ten patients (aged 35 to 70 years) with neurologic adductor spastic dysphonia rated themselves on a 7-point scale of severity for degree of voice improvement and physical effort after a series of three injections of botulinum toxin. Symptoms were noticeably reduced 24 and 48 hours after injection; this improvement was followed by considerable fluctuations in voice quality and phonatory effort. With successive injections, patients differed in their post injection experiences, the time required to reach optimal voice, and the total duration of benefit. The study shows that the course of voice change after botulinum toxin injection is not predictable, uniform, or equal among patients with spastic dysphonia. PMID- 8502105 TI - Extended middle fossa resection of petroclival and cavernous sinus neoplasms. PMID- 8502106 TI - Patient use of 'telemetric' ENG to register nystagmus in the private sphere. PMID- 8502107 TI - Directory of otolaryngological societies. PMID- 8502108 TI - Endoscopic sinus surgery for inverting papillomas. PMID- 8502109 TI - Treatment of otosyphilis. PMID- 8502110 TI - Study on the metabolism of lyso-platelet activating factor (lyso-PAF) in human paranasal sinus mucosa. The cultured ciliated epithelium can convert lyso-PAF to PAF. AB - The conversion of lyso-platelet activating factor (lyso-PAF) to PAF in cultured paranasal sinus mucosa obtained from normal human subjects was studied. The PAF concentration in the medium was determined after addition of lyso-PAF. PAF became detectable at 10 minutes after the addition of 10(-8)M lyso-PAF, and reached a maximum concentration (3.25 x 10(-9)M) at 20 minutes. The PAF level then gradually declined to become undetectable at 60 minutes after addition of lyso PAF. Thus PAF is very unstable having a half-life calculated to be 12.8 minutes with an elimination constant of k = 0.05377 minutes-1. In contrast, lyso-PAF is known to be a stable metabolite of PAF as well as a precursor of PAF. The results obtained from this study suggest that the turnover of lyso-PAF to PAF may play a role in evoking prolonged inflammation in target organs or tissues. PMID- 8502111 TI - Vasorelaxant effect of the potassium channel activator, RWJ 29009, is tissue selective. AB - Potassium channel activators have potential cardioprotective properties, in part due to their ability to increase coronary blood flow. We compared the vasorelaxant properties of potassium channel activators, a calcium channel blocker (nicardipine) and a direct smooth muscle relaxant (sodium nitroprusside) in the canine coronary artery, the femoral artery and the saphenous vein precontracted with 0.03 microM endothelin-1. In the circumflex coronary artery, RWJ 29009, a novel and potent potassium channel activator, maximally relaxed the precontracted rings with an EC50 of 1.9 nM. Cromakalim (EC50 = 220 nM) and nitroprusside (EC50 = 109 nM) were also active. Nicardipine (EC50 = 16.6 nM) produced only a 70% relaxation at 1 microM concentration. In both femoral artery and saphenous vein, all agents relaxed the precontracted rings only at much higher concentrations, and the relaxations were only 75% of maximal relaxation. The results show that while all vasodilators preferentially relax the coronary artery, potassium channel activators appear to be the most selective and potent of these agents. PMID- 8502112 TI - Effect of nitrous oxide exposure on maternal and embryonic S-adenosylmethionine levels and ornithine decarboxylase activity. AB - Nitrous oxide is suspected to be a developmental toxicant in humans. The anesthetic does produce increases in the resorption and malformation frequencies in rodents. The mechanism for the drug's developmental toxicant effects is unknown. Embryonic DNA synthesis is decreased; however, this decrease does not appear to be due to depressed levels of adenine or guanine. In this investigation, we examined the effect of N2O on maternal and embryonic S adenosylmethionine (AdoMet) levels and ornithine decarboxylase (ODC) activity, and the effect of exogenous methionine (Met) on these parameters was also examined. AdoMet and ODC are involved in polyamine synthesis, and polyamines are involved in regulation of macromolecular synthesis. Pregnant rats were treated with N2O for 24 hours beginning on the morning of day 10 of gestation. There was no effect of N2O on maternal hepatic AdoMet or S-adenosylhomocysteine (AdoHcy) levels; there was also no effect on embryonic AdoMet. Embryonic AdoHcy could not be detected in many of the samples; however, N2O treatment did significantly increase the number of embryonic samples in which AdoHcy was detectable. ODC activity was not affected by either treatment in dams but was increased by N2O in embryos. It is possible that the embryotoxic effect of this anesthetic is mediated by alterations in the AdoMet to AdoHcy ratio or to changes in ODC activity and polyamine synthesis. PMID- 8502113 TI - Circadian rhythm of cortical and striatal adenosine receptors. AB - In order to investigate diurnal variations in binding parameters of A1 and A2 adenosine receptors, Kd and Bmax were calculated in mice that had been housed under controlled light-dark cycles for 4 weeks (light on from 7.00 to 19.00 h). A1 cortical receptors were labelled by N6-cyclohexyl-[3H]adenosine, and A1 and A2 striatal receptors by 5'-N-ethylcarboxamido[8-3H]adenosine. Significant differences were found for Bmax values measured at 3-h intervals across a 24-h period. Cyclic variations of the number of binding sites were shown, with a minimum number of A1 and A2 receptors during the light period and a maximum during the dark period. The amplitude for cortical A1 receptors, between 03.00 and 18.00 h, was 39%, while for striatal A1 receptors, between 03.00 and 15.00 h, was 92%. The amplitude for the A2 striatal receptors, between 03.00 and 15.00 h, was 147%. No substantial rhythm was found in the Kd values. These differences in the amplitude could suggest a different physiological modulation of the two adenosine receptor subtype moiety which could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system. PMID- 8502114 TI - Hydroquinone simultaneously induces indole amine 2,3 dioxygenase (IOD) and inhibits tyrosinase in Bufo melanostictus. AB - Hydroquinone administration in Bufo melanostictus causes an induction of indole amine 2,3-dioxygenase in skin and liver while simultaneously inhibiting tyrosinase in these organs. The result is discussed with the reports of higher urinary excretion of abnormal indole metabolites including derivatives of anthranilic acid in vitiliginous subjects (Roychoudhury and Chakraborty, Clinica. Chim. Acta 22, 298, 1968; Kurbanov and Berezov, Vopr. Med. Khim. 22, 683, 1976). PMID- 8502115 TI - In vitro glycation and acetylation (by aspirin) of rat crystallins. AB - In vitro studies with rat lens crystallins were conducted to explore the mechanism by which aspirin (ASA-acetylsalicylic acid) could inhibit cataractogenesis. The purpose of the present study is to show whether gamma crystallin is the primary target for glycation by glucose and acetylation by ASA. Lens soluble fractions from one and seven month old Sprague-Dawley rats were incubated with 5 mM [14C]glucose with and without 10 mM ASA. alpha, beta, and gamma-crystallins were separated by molecular sieve HPLC and specific activities of each crystallin determined. In vitro acetylation was also studied by measuring protein bound [14C]acetyl groups after incubation with [14C]acetyl ASA. There was 2 to 4-fold faster glycation of gamma-crystallin than all other crystallins from 1-month-old rats and ASA inhibited glycation of gamma-crystallin four times more than that of alpha and beta-crystallins, thus showing preferential glycation of gamma-crystallin and its selective inhibition by ASA. [14C]acetyl incorporation showed increased acetylation of gamma-crystallin in one month old rats, whereas in older lenses acetylation of other crystallins predominated. Treatment with 10 mM ASA showed 35% decrease in free -NH2 groups but protein thiols remained unchanged. PMID- 8502117 TI - Dose response characteristics for the hyperglycemic, hyperlactemic, hypotensive and hypocalcemic actions of amylin and calcitonin gene-related peptide-I (CGRP alpha) in the fasted, anaesthetized rat. AB - Amylin, a 37 amino-acid peptide secreted from the pancreatic beta-cells, exerts marked effects on carbohydrate metabolism in intact rats. It has approximately 50% amino-acid identity with the calcitonin gene-related peptides (CGRP) as well as certain shared biological actions. In vivo potencies were determined for four responses (increases in plasma glucose, increases in plasma lactate, decreases in plasma calcium, and depression of arterial pressure). These responses were measured in fasted, lightly anaesthetized rats given single intravenous bolus injections of rat amylin or rat CGRP alpha at doses of 0.01, 0.1, 1, 10, 100 and 1000 micrograms (about 7 pmol/kg-700 nmol/kg). Control animals received an equal volume of saline. The order of potency for the different responses was as follows: (i) increase in plasma glucose concentration, amylin approximately 2 times more potent than CGRP (by ED50) with detectable responses occurring at doses 100-fold less; (ii) decrease in plasma total calcium concentration, CGRP of equal or greater potency than amylin; and (iii) decrease in arterial pressure, CGRP 44-fold more potent than amylin. An increase in plasma lactate occurred with amylin doses 1000-fold lower than the CGRP doses producing such effects. Saturation of the dose-dependent increase in lactate was not observed, so median effective doses (ED50) were not obtained. These results are consistent with the existence of separate receptor systems for amylin and CGRP. The effects of amylin on plasma glucose and lactate concentrations were demonstrable at doses of 0.1 1.0 micrograms (70-700 pmol/kg). These doses produced plasma levels that were within the concentration range previously reported for insulin-resistant rats, supporting the proposal that amylin is a physiologic endocrine regulator of carbohydrate metabolism in vivo. PMID- 8502116 TI - Comparative effects of dehydroepiandrosterone and related steroids on peroxisome proliferation in rat liver. AB - Dehydroepiandrosterone (DHEA) is known to induce peroxisome proliferation and peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) mRNA in the rat liver. We have compared the effects of 6 intermediate metabolites of DHEA on the induction of peroxisome proliferation and PBE mRNA. Administration of epiandrosterone, etiocholanolone, androstenedione, estrone or estradiol for 2 weeks in the diet at 0.45% concentration to adult male F-344 rats failed to induce significant increases in peroxisome proliferation and PBE mRNA when compared to the parent compound DHEA. Dietary administration of 5-androstene-3 beta,17 beta-diol (ADIOL) for 2 weeks at 0.45% concentration caused an increase in PBE mRNA and peroxisome proliferation but to a lesser extent than DHEA. Following a single intragastric dose of DHEA an increase in PBE mRNA level was observed in the liver at 1 hr and continued to 16 hrs., but not with its metabolites. These results strongly suggest that DHEA or possibly another yet to be identified metabolite might be responsible for peroxisome proliferation. PMID- 8502118 TI - Endogenous morphine and codeine in mice--effect of muramyl dipeptide. AB - Administration of morphine exerts many effects on the immune system. On the other hand little attention has been paid to the fact, that endogenous morphine and codeine exists in mammals, including man. This raises the question, whether or not endogenous opiate alkaloids play some role in immunoregulation. In addition muramyl-dipeptide (MDP), product of bacterial cell wall degradation and a potent immunomodulatory agent exhibits a broad spectrum of effects including effects on CNS functions. The present study investigated whether or not the endogenous levels of morphine and codeine are affected by administration of MDP in mice. Marked variation was found in spleen, brain, small intestine and heart in morphine and codeine concentrations. The intraperitoneal administration of MDP produced a significant increase in tissue morphine levels 30 minutes after injection. PMID- 8502119 TI - Cocaine, amphetamine and cathinone, but not nomifensine and pargyline increase calcium inward current in internally perfused neurons. AB - The influence of cocaine, amphetamine, cathinone, pargyline and nomifensine on inward calcium current was studied using internally perfused neurons of the snail Lymnaea stagnalis. While nomifensine and pargyline inhibited inward calcium current in the concentrations 10(-7)-10(-4) M and did not affect them in the concentrations 10(-9)-10(-8) M, cocaine, amphetamine and cathinone had a biphasic action on inward calcium current, causing activation (10-30 percent) at 10(-9) 10(-7) M, and inhibition at higher concentrations. Only cathinone caused a shift of the I-V characteristics of the membrane along the potential axis. It is suggested that drugs of abuse affect membrane excitability and inward calcium current in neurons directly. PMID- 8502120 TI - Recent advances in chronopharmacokinetics: methodological problems. AB - Chronopharmacokinetics deals with the study of the temporal changes in absorption, distribution, metabolism and elimination and thus takes into account the influence of time of administration on these different steps. In the last decade, numerous studies have been devoted to chronokinetics: recent advances will be reviewed in the first part. As representative examples, the main chronokinetic changes of anaesthetics, cardiovascular active drugs and antiinflammatory drugs in men are listed. Temporal changes can be involved at each step of the sequence of pharmacokinetic processes: temporal variations in drug absorption from the gastro-intestinal tract, in plasma protein binding and drug distribution, in drug metabolism (temporal variations in enzyme activity, hepatic blood flow) and in renal drug excretion may play a role. Thus, the time of administration of a drug is an important source of variation which must be taken into account in kinetic studies and particular methodological aspects of chronokinetics are needed. In a chronopharmacokinetic study many factors of variation must be controlled: factors related to the drug itself (influence of food, galenic formulation, drug interactions), subject related-factors (age, gender, pathology, posture, exercise, synchronization) and factors related to the conditions of the administration (single or repeated dosing, constant rate delivery, route of administration). In conclusion, there are some instances in which a chronokinetic study is needed: 1) when possible daily variations in pharmacokinetics may be responsible for time dependent variations in drug effects, 2) when drugs have a narrow therapeutic range, 3) when symptoms of a disease are clearly circadian phase-dependent (e.g. nocturnal asthma, angina pectoris, myocardial infarction, ulcer disease) 4) when drug plasma concentrations are well correlated to the therapeutic effect in case the latter is circadian phase-dependent. Variables influencing pharmacokinetics such as fasting, meals and meal times, galenic formulation, posture, activity-rest, have to be controlled according to the aim of the investigation. The main aim of chronokinetic studies is to control the time of administration which among others, can be responsible for variations of drug kinetics but also may explain chronopharmacological effects observed with certain drugs. PMID- 8502121 TI - Peripherally administered serotonin induces hyperglucagonemia in mice. AB - Peripherally administered serotonin (5-HT) induced a marked increase in the plasma glucagon level in mice. The hyperglucagonemic effects of 5-HT were completely antagonized by methysergide, ketanserin and ritanserin which have a high affinity for 5-HT2 receptors. However, the 5-HT3 receptor antagonist ICS 205 930 and MDL 72222 were without effect. These findings suggest that the activation of the peripheral 5-HT2 receptor induces the increase in plasma glucagon level and that these receptors may play a role in the release of glucagon. PMID- 8502122 TI - Comparison of two radioiodinated ligands of dopamine D2 receptors in animal models: iodobenzamide and iodoethylspiperone. AB - Several iodinated compounds have been developed for in vivo exploration of dopamine D2 receptors by SPECT. It is of great value to understand if the same information could be obtained with different radioligands. For this purpose, we compared in vivo properties of two iodinated ligands, iodoethylspiperone (IES) and iodobenzamide (IBZM), using different pharmacological and lesioning treatments in rats. Cerebral biodistribution performed by ex vivo autoradiograms and dissection of brain areas showed that IES and IBZM bound specifically to D2 receptors since a pre-injection of haloperidol prevented accumulation of both ligands. In contrast, when haloperidol was injected after IES or IBZM, only IBZM was displaced from its binding sites. This could be explained partly by a process of dopamine-dependent internalization with IES. The response to striatal quinolinic acid infusion for lesioning post-synaptic neurons was very different for IES and IBZM. In this model a decrease in IBZM accumulation occurred, corresponding to the loss of D2 receptors located on post-synaptic neurons. In contrast, a unexpected increase in IES accumulation was observed on the lesioned side. From these results we concluded that IES and IBZM, two iodinated ligands belonging to different pharmacological families, bound specifically to dopamine D2 receptors. However they have different properties in animal models. Therefore, it appears that IBZM is a more suitable ligand than IES to detect modifications of D2 receptors by in vivo exploration. PMID- 8502123 TI - Contribution of gastrin to cysteamine-induced gastric acid secretion in rats. AB - The role of circulating gastrin in cysteamine induced gastric acid secretion was examined in conscious male Wistar rats, provided with a portal vein catheter, a jugular vein catheter and a pyloric drainage tube. Intravenous infusion of 0.3 nmol/kg.30 min of gastrin 17-l resulted in serum gastrin concentrations of 1138 +/- 151 pg/ml and gastric acid secretion of 104 +/- 36 mumol H+/kg.30 min. This acid response was abolished by intravenous injection of 60 microliters of a gastrin-antiserum, indicating the efficacy of immunoneutralization with this antiserum in vivo. Intravenous bolus administration of 125 mg/kg of cysteamine induced increases in serum gastrin concentration (864 +/- 96 pg/ml) and gastric acid outputs (107 +/- 27 mumol H+/kg.30 min) not significantly different from the gastrin 17-l infusion experiments. Gastrin antiserum abolished cysteamine-induced gastric acid secretion, indicating that gastric acid secretion induced by 125 mg/kg of cysteamine is largely mediated by circulating gastrin in rats. PMID- 8502124 TI - Plasma natriuretic factor(s) in patients with intracranial disease, renal salt wasting and hyperuricosuria. AB - To test our hypothesis that a circulating factor(s) may be causing the renal salt and urate wasting in patients (pts) with intracranial diseases, we exposed rats to the plasma of these patients and studied sodium and lithium transport. We selected 21 neurosurgical pts, 13 of whom had increased fractional excretion (FE) of urate, and 14 age and sex-matched controls. Plasma from pts and controls were injected IP (0.5 mL) and infused, 0.2 ml prime and 1.8 mL at 0.01 mL/min, to Sprague Dawley rats anesthetized with Inactin. Renal transport of sodium (Na), lithium (Li) and potassium (K) was determined. There were higher mean +/- SEM for FENa, 0.59 +/- 0.07% vs 0.29 +/- 0.05%, P < 0.01, FELi, 36.6 +/- 1.9% vs 24.0 +/- 1.6%, P < 0.001 and K excretion rates, 1.69 +/- 0.13 vs 1.31 +/- 0.09 mumol/min, p < 0.02, in rats infused with plasma of pts as compared to controls, respectively. FENa decreased with increasing dilution of plasma of 2 pts with ICD. There was no difference in mean weight of rats, blood pressure, urine flow rate or insulin clearance between pts and controls. These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption. PMID- 8502125 TI - Mesangial cell proliferation is directly enhanced by sera from patients with renal insufficiency. AB - We undertook the present study to determine whether there is a direct effect of sera from patients with renal insufficiency on mesangial cell proliferation. Growth-arrested mesangial cells were incubated with sera from patients with varying degrees of renal insufficiency and then pulsed with [3H]thymidine. Thymidine uptake was progressively greater with more advanced renal failure and was linearly correlated with (creatinine)-1. This data suggests that serum from patients with loss of renal function contains mitogens capable of directly enhancing mesangial cell proliferation. PMID- 8502126 TI - Neuropeptide Y inhibits pertussis toxin-catalyzed ADP-ribosylation in bovine adrenal chromaffin cell membranes. AB - Evidence is presented that the neuropeptide Y receptor is directly coupled to an inhibitory G protein existing in cultured bovine adrenal chromaffin cell membranes. Pertussis toxin catalyzes the [32P]ADP-ribosylation of a 41 kDa plasma membrane protein. 5'-Guanylylimidodiphosphate inhibited the [32P]ADP labelling of this protein in a dose-dependent manner whereas GTP had no effect. Preincubation of the plasma membranes with high concentrations of neuropeptide Y followed by a brief exposure to a low concentration of 5'-guanylylimidodiphosphate significantly inhibited ADP-ribosylation beyond that observed with 5' guanylylimidodiphosphate alone. These results suggest that the neuropeptide Y receptor in bovine adrenal chromaffin cells is directly coupled to a 41 kDa PTX substrate (presumably the alpha subunit of an inhibitory G protein). PMID- 8502127 TI - Detection of endothelin 1,2 and endothelin-like immunoreactant in wound surface and plasma in mice with thermal injury. AB - Endothelin is a well known vasoconstrictive peptides produced by endothelial cells and has been reported to regulate the systemic circulation. The authors investigated changes in endothelin in plasma and the surface of wounds induced with thermal injury using an experimental ear burn model in mice. At 0, 15, 30, 60, 120 and 180 minutes after thermal injury the plasma endothelin-like immunoreactant levels were 1.50 +/- 0.21, 1.86 +/- 0.36, 2.81 +/- 0.55, 2.62 +/- 0.27, 1.54 +/- 0.14 and 1.25 +/- 0.19 fmol/ml (N = 8), respectively. Endothelin like immunoreactant levels in the plasma increased gradually until 30 minutes after the thermal injury. Endothelin-like immunoreactant content in the ear before thermal injury and at 60 minutes after injury were 7.04 +/- 0.64 and 8.61 +/- 1.24 fmol/ear (N = 8), respectively. The change in endothelin-like immunoreactant after thermal injury originated from endothelin 1,2; that is, the endothelin-1,2 content of the burned ear increased significantly 15 and 60 minutes after thermal injury to 12.52 +/- 0.68 and 11.58 +/- 1.04 fmol/ear, respectively, compared with 1.78 +/- 0.91 fmol/ear (N = 8) obtained before injury. These results suggested that endothelin 1,2 existed in the region of the wound caused by thermal injury. PMID- 8502128 TI - Tentativeness and fervor in cell biology require negative and positive feedforward control. AB - End-product feedback regulates early steps in metabolic pathways, affecting activation and the rate of end-product synthesis. Early formation of end-product also modifies later steps in the synthesis of end-product. We designate this form of regulation feedforward. Negative feedback/feedforward by end-products may result in homeostasis, but also in physiologic tentativeness. Positive feedback/feedforward by end-product gives rise to fervid events. Tentativeness and fervor, due to negative and positive feedforward rather than feedback, explain otherwise puzzling aspects of immunology and endocrinology. PMID- 8502129 TI - The influence of gender in the evaluation of platelet and plasma catecholamines. AB - The platelet and plasma levels of catecholamines (CA) were simultaneously studied in a group of normal subjects in order to find possible sex-related changes in the distribution of CA in these two compartments. No significant differences between males and females were observed, but a marked platelet noradrenaline increase was found in the luteal phase as compared to the follicular phase. Furthermore, the platelet and plasma CA levels were strongly correlated in the male group but not in the female group. These results, while confirming the existence of a menstrual-related variability in noradrenergic activity, suggest a sex-related difference in the dynamic balance between platelet and plasma CA levels. The simultaneous assay of platelet and plasma CA enabled this phenomenon to be revealed, whereas the separate evaluation of platelet or plasma CA levels would not have done so. PMID- 8502130 TI - Alkaline phosphatase activity during sphinganine potentiation of retinoic acid induced differentiation of human promyelocytic leukemia cell line, HL-60. AB - Sphinganine (SP) pre-treatment potentiated the retinoic acid (RA)-induced (4-96h exposures) differentiation and increase of alkaline phosphatase (ALP) activity. A higher percentage of SP pre-treated cells in RA exposures resembled mature myelocytes or granulocytes; greater increase in ALP activity was observed. In cells exposed to RA alone for only a period of 24h, the ALP activity could still increase and reach a similar maximum ALP activity (8.5-10.0 units/mg protein) at 48h as it was under continuous RA treatment. In all cells with longer exposures (24-96h) to RA, SP pre-treatment increased ALP activity to more or less the same higher maximum (14.0-15.5 units/mg protein). SP, added 24h before or concomitantly, but not 24 nor 48h after the addition of RA, could potentiate the RA-induced differentiation and increase of ALP activity. PMID- 8502131 TI - Occurrence and partition of the beta-carboline norharman in rat organs. AB - The beta-carboline norharman was determined in plasma, brain, liver, kidney, spleen, heart and lung of the rat using HPLC with fluorescence detection. In order to improve the speed and sensitivity of this assay an earlier published sample clean-up extraction procedure and HPLC method were adjusted. Norharman was found to be present in plasma as well as in all organs tested, concentrations in organs being about 80 times higher than those in plasma. Intraperitoneal injections of 2 and 100 mg/kg norharman showed that the partition of norharman between organs and plasma is about 3. Only the highest dose was found to have behavioural effects, viz. alerting reactions, a decrease in motor and exploratory activity, sedation, loss of righting reflex and after 30 min complete muscle relaxation, but no catatonia was observed. Norharman was found to be metabolized by the liver with a half live of about 20 min, whereas all other organs tested did not show any norharman clearing capacity. The results suggest that norharman is not likely the cause of psychosis, but a natural sedative and by- or coproduct of a more primary biochemical derangement. PMID- 8502132 TI - Influence of non-L-type calcium channel antagonists on phencyclidine-induced effects in rats. AB - Omega-conotoxin (1 and 2 micrograms/10 microliter i.c.v.), a N-type calcium channel blocker, and amiloride (7.5 and 15 micrograms/10 microliter i.c.v.), a T type calcium antagonist, significantly prevented the EEG and behavioural effects induced by phencyclidine (PCP, 5 mg/kg i.p.) in rats. In accordance with previous studies showing the significant influence of L-type calcium blockers in the same model, these results confirm that the modulation of calcium currents plays a key role in the expression of PCP-induced effects. PMID- 8502133 TI - Effects of cocaine on fetal and postnatal development in mice. AB - The goal of the current investigation was to study the effect of in utero exposure of cocaine on fetal and postnatal development. 48 adult female NIH Swiss mice were used as experimental animal models. Each of the 24 mice were injected intraperitoneally with cocaine HCl at a daily dose level of 45 mg/kg (body weight). Each of the 24 control animals were daily injected with saline. One week after the treatment started, one male was introduced into each female cage. The day the vaginal plug was found was recorded as day one of pregnancy. Both cocaine treated and saline treated animals were subdivided into three subgroups each with 8 animals in each subgroup. Subgroup one was used to obtain midgestational (11 day) fetuses, subgroup two was used to obtain full term fetuses (18 day) and subgroup three was used to obtain pups. Individual fetal weights were taken and each fetus was examined for developmental anomalies. Midgestational fetuses exposed to cocaine had lower body weights than those of the controls. The full term fetuses, however, had similar weight in both experimental and control groups. The pups were weighed every 2 days from day 2 to day 16. The pups showed a slightly wider range of weights in the cocaine treated group as they matured to 16 days. All fetuses and pups revealed no soft tissue anomaly which, along with the weight data, supported our earlier findings. PMID- 8502134 TI - [The use of pulse oximetry in anesthesiology]. PMID- 8502135 TI - [Principles and algorithms for determining blood oxygenation from pulse oximeter measurements]. PMID- 8502136 TI - [A comparative study of five pulse oximeters]. AB - The pulsed oximeters "Satlite" and Satlite Trans" (Datex, Finland), "Biox-3700' (Ohmeda, USA) "OXI" (Radiometer, Denmark), "Danamap-Oxytrak" (Critikon, Johnson & Johnson, USA) are essential and highly precise devices for controlling vital functions of the body during anesthesiologic techniques. The delay time of a response of the pulsed oximeters "Satlite Trans" and "Box-3700" in providing the values of the saturation of arterial blood hemoglobin with oxygen is 40 sec. The pulsed oximeter-personal computer system opens up new possibilities of increasing the quality of monitoring and safety of bronchoscopic studies and operations and allows a protocol of the intervention to be developed. PMID- 8502137 TI - [A proportional electric pneumatic regulator and prospects for its use in apparatus for artificial ventilation of the lungs]. PMID- 8502138 TI - [A study of the thermal regimens of biological tissue and optimization of the parameters of action in local therapy with a low-temperature gas stream]. PMID- 8502139 TI - [Pulse oximetry--a basis of safe anesthesia]. PMID- 8502140 TI - [Comparative characteristics of the irradiation homogeneity of blood in different devices for ultraviolet radiation of the blood]. AB - The value of blood irradiation homogeneity is defined. Some patterns of flowing blood and ultraviolet irradiation are considered. The most homogeneous irradiation has been shown to be reached when the free surface of blood is irradiated. For six different devices, the value of blood irradiation homogeneity is calculated according to the values defined. A new device for ultraviolet flowing blood irradiation is proposed, which allows the greatest value of blood irradiation homogeneity from the known to be obtained. PMID- 8502141 TI - [Use if the pulse oximeter in the intensive therapy and anesthesiology of children]. PMID- 8502142 TI - [The ELON-001 device for evaluating the intensity of the regulatory processes of the body]. PMID- 8502143 TI - [Realization of a membrane gas exchange system using perfluorodecalin]. PMID- 8502144 TI - [Stabilograph]. PMID- 8502145 TI - [Basic stages in the development of photo-oxyhemometry]. PMID- 8502146 TI - [The APC-2 x-ray diagnostic photographic apparatus]. AB - The paper describes the pattern of a X-ray diagnostic apparatus for films and tomography, which has "Storens" and "Stors" Russian working places distinguishing for their high operating characteristics. It also presents the angles and velocities of tomography. The apparatus is equipped with a 50-kW microprocessor controlled feeder. The results of clinical trials of the device are positive. PMID- 8502147 TI - [The possibilities of using fiber optic luminescent light sources in medical biological studies]. AB - The use of optical fibers with luminescent spectrum-displacing admixtures inserted into their core enables the prototherapeutic devices to be designed. The paper provides the principle for designing optofiber luminescent light sources. Experiments with laboratory animals and donor blood have indicated that incoherent homogeneous light may produce effects in regenerating damaged tissue surfaces. PMID- 8502148 TI - [The selection and rationale of a scheme for the construction of cryotherapeutic equipment for local cooling of biological tissue]. PMID- 8502149 TI - [The application of the sample recognition theory for a system of surgical diagnosis in microsurgery]. AB - The paper outlines the applicability of the sample recognition theory to process the data obtained with the use of multifiber optical catheters as part of information systems for diagnostics and visualization for microsurgery. A specific example of synthesizing the image assessment algorithm by employing the sample recognition theory is considered for the visualization system for a laser angioplastic unit. PMID- 8502150 TI - [A method of calculating the parameters of multifiber optic catheters]. AB - The paper underlines the necessity of taking into account the relationship of the basic characteristics of multifiber optical catheters, such as the number, position, and diameters of some fibers, to the informational potentials of diagnostic and imaging systems of the basis of the catheters. The relationship is established by applying discretization theorems. The main points are illustrated by an example of practical angioplastic calculation. PMID- 8502151 TI - [A device for studying respiratory mechanics by the forced oscillation technique]. AB - A new compact device for measuring respiratory impedance is designed. Input respiratory impedance, an impedance of upper airways and respiratory impedance corrected for upper airways shunt can be measured in 2 minutes. The space condition requirements are complied by integrating an oscillation generator, sensors, a mouthpiece with a screen and a reference resistor in the measuring head. The oscillation generator produces small-amplitude forced oscillations (with a tidal volume of about 1 ml) at frequencies f = 7, 10, 13, 16, and 19 Hz. Algorithms of calibration and measurement provide impedance calculation. For 55 different external impedances, complex transmission factors are measured for each of the five frequencies. The standard deviation of amount and phase of complex transmission factors are less than 5% and 0.06, respectively. PMID- 8502152 TI - [Three-dimensional planning of remote gamma therapy on a personal computer]. PMID- 8502153 TI - [A study of the filling of a balloon catheter sheath during inflation]. PMID- 8502154 TI - [Low-silver and silver-free x-ray materials for medical diagnosis]. PMID- 8502155 TI - [Development and production of equipment for extracorporeal blood purification in the PEHAPT Association]. PMID- 8502156 TI - [An automated system for preventive medical examinations at large enterprises]. PMID- 8502157 TI - [Restorative operations on the aortofemoral segment of the iliac artery using a new vascular suturing device]. PMID- 8502158 TI - [Electronic circuits for measuring the level of cryo-agents and regulating heat release for cryogenic apparatus]. PMID- 8502159 TI - [The "Polius-3" apparatus for magnetotherapy and magnetophoresis]. PMID- 8502160 TI - [Modeling in x-ray equipment manufacture]. PMID- 8502161 TI - Methylation of adenine and cytosine in some strains of Fusobacterium nucleatum. AB - DNA from six strains of Fusobacterium nucleatum was examined for possible methylation of adenine or cytosine in the restriction site GATC. F. nucleatum DNA was digested with the restriction enzymes Sau3AI, DpnI and MboI, subjected to electrophoresis in agarose gels and Southern blotting. The blots were hybridized with a polymerase chain reaction (PCR)-amplified DNA probe. Both radioactive and non-radioactive labeling methods were used. Some strains of F. nucleatum were found to be dam methylated or dcm methylated in the sequence GATC; the adenine residue is methylated in strain ATCC 10953, while the cytosine residue is methylated in the strains F1 and F3. Strains F6, ATCC 25586 and Fev1 are probably not methylated in this nucleotide sequence. PMID- 8502162 TI - Adherence of Candida albicans to immobilized extracellular matrix proteins is mediated by calcium-dependent surface glycoproteins. AB - The adherence of Candida albicans to the extracellular matrix proteins type I collagen and fibronectin (Fn) is dependent upon the presence of extracellular calcium. In the absence of calcium, 14 +/- 3% of yeast cells added to type I collagen adhered, whereas 62 +/- 3% of yeast cells adhered in the presence of 2 mM calcium. EDTA and EGTA reduced C. albicans adherence in a dose-dependent manner. Calcium, and to a lesser extent, cesium and magnesium, enhanced yeast cell adherence. The fluorescent probe, terbium (Tb+3), bound to the surface of yeast cells in a dose-dependent manner demonstrating the presence of cationic metal-binding sites on the yeast cell surface. When extracts of C. albicans yeast cells were applied to columns of Fn or gelatin coupled to agarose, two surface proteins of C. albicans were specifically eluted with 10 mM EDTA, 2% alpha methylmannopyranoside or an Arg-Gly-Asp-containing peptide. The fungal proteins had relative molecular masses of 60,000 and 105,000 in the unreduced state. The proteins were present in the cell membrane as well as the cell wall and were demonstrated to be glycoproteins by their ability to bind concanavalin A. Immunoblot analysis of yeast extracts demonstrated that anti-integrin antibodies to the human fibronectin, vitronectin and complement receptor cross-reacted with the Candida 60 kDa glycoprotein. Thus, calcium-dependent fungal cell wall glycoproteins likely related to integrins may be receptors responsible for yeast cell adherence to host tissue such as the extracellular matrix. PMID- 8502163 TI - Stimulation of secretory antibodies against Bordetella pertussis antigens in the lungs of mice after oral or intranasal administration of liposome-incorporated cell-surface antigens. AB - Lipopolysaccharide (LPS) and outer membrane protein (OMP) preparations of Bordetella pertussis were incorporated into multilamellar liposomes composed of soya bean-derived phospholipids which were then used for oral and intranasal immunization of mice. Specific antibody responses of animals immunized by either route were measured in lung washes. A specific IgA response to LPS was detected after immunization with the OMP-containing liposomes but not with the LPS containing liposomes, indicating adjuvant activity of the proteins. The OMP containing liposomes were significantly more effective in inducing immune responses than the OMP preparation alone. Responses were highest when mice were given a booster 30 days after primary immunization. Maximum responses occurred 20 days after the booster but specific antibody was still detected 75 days after the secondary immunization. These results suggest that this liposome antigen delivery system has potential in stimulating secretory antibody responses which may be helpful in protecting against infection from B. pertussis. PMID- 8502164 TI - Exchange of phospholipids between Escherichia coli cells and environment. AB - We studied the exchange of phospholipids between Escherichia coli K-12 cells and the suspension medium containing inactivated guinea-pig serum. In this medium, the release of 3H-labelled phospholipids was proportional both to the quantity of serum and to the temperature of incubation. No phospholipids were released when no guinea-pig serum was added to the medium, or the incubation temperature was 4 degrees C. The release of phospholipids into the medium was accompanied by an uptake of serum phospholipids by the cells, as demonstrated by incorporation of labelled phospholipids from the suspension medium. We conclude that an exchange occurs between the cellular phospholipids and those of the medium. Control tests with 3H-thymidine showed that cellular lysis was not involved. PMID- 8502165 TI - Immunization of mice with Salmonella typhimurium C5 aroA expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin. AB - An attenuated Salmonella strain expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin was constructed by first transforming a methylation-positive, restriction-negative Salmonella with plasmid pJCP20M, a derivative of pBR322 containing the modified pneumolysin gene. Plasmid DNA was then extracted and transformed into Salmonella typhimurium C5 aroA. The transformant (denoted JM8) was capable of constitutively expressing the modified pneumolysin gene in vitro and stably maintained the recombinant plasmid containing the pneumococcal DNA, even in the absence of antibiotic selection. When JM8, or the parental Salmonella C5 aroA carrying pBR322 (denoted JM6), were administered orally to mice, both strains were capable of at least transient colonization of the Peyer's patches. Sera from JM8 mice (but not those fed JM6) had significant anti-pneumolysin IgG and IgA ELISA titres. Intraperitoneal administration of JM8 resulted in higher anti-pneumolysin IgG titres, but lower specific IgA levels. PMID- 8502166 TI - Primary Candida pneumonia. Experience at a large cancer center and review of the literature. AB - We reviewed the experience over 20 years with primary Candida pneumonia among fatal cancer cases at our hospital. Unequivocal evidence of primary Candida pneumonia has been reported in only 55 cases. We report here 31 such cases. Unlike patients with disseminated candidiasis, and contrary to previous studies concentrating on cancer patients, only 9 of our 31 patients had severe neutropenia. In this report, the lack of organ involvement other than the lungs at complete autopsy examination, the exclusion of patients with candidemia, the very high percentage of intrabronchial and intra-alveolar fungal involvement without vascular invasion, and the concomitant presence of candidal esophagitis in some patients suggest that the mechanism of entry of the infectious particles may have been aspiration of oropharyngeal contents. The major clinical manifestations of primary Candida pneumonia are fever and tachypnea. Radiologically, nonspecific patchy infiltrates can be seen. Histopathologically, there is prevalence of bronchopneumonia, hemorrhage, and necrosis. The only accepted criterion for the definitive diagnosis of Candida pneumonia is histologic demonstration of the fungus in lung tissue. In contrast to previous reports, we demonstrated that primary Candida pneumonia can be life-threatening in patients with cancer since it directly contributed to the death of 84% of the patients in the present series. Very little data are available on the therapy and outcome of patients with Candida pneumonia. However, primary Candida pneumonia in the compromised host should be treated as a life-threatening infection with systemic antifungal therapy. PMID- 8502167 TI - Candida krusei fungemia. Report of 4 cases and review of the literature. AB - Candida krusei has recently been increasingly recognized as a pathogen in immunocompromised patients with malignancies. We report four immunocompromised patients with C. krusei fungemia and review the literature. Including our 4 cases, 62 cases of C. krusei fungemia were identified in the literature. Detailed information was available for only 25 patients. The clinical features of patients with C. krusei fungemia are similar to those reported for Candida tropicalis. Most patients were neutropenic and more than one half of the patients had received antifungal therapy and had evidence of gastrointestinal mucosal breakdown before the development of C. krusei fungemia. The overall mortality was 48%. Patients treated with regimens containing amphotericin B had improved survival over patients who received no therapy. Favorable response rates were higher in patients receiving high-dose amphotericin B or high-dose amphotericin B plus flucytosine when compared to patients treated with low-dose amphotericin B. PMID- 8502168 TI - The lung in inflammatory bowel disease. AB - Respiratory involvement in patients with inflammatory bowel disease (IBD) has been reported mainly since 1976. This form of involvement should clearly be separated from interstitial lung disease due to sulfasalazine or mesalamine, although the distinction may be difficult in some cases. We report the data of an ongoing Registry containing 33 cases (23 cases receiving no drug therapy) with ulcerative colitis or, less often, Crohn's disease, who developed varied bronchopulmonary problems. In several cases, the exact diagnosis and the relation of the bronchopulmonary disease to IBD had not been established for many years, thus delaying effective treatment with steroids. In most cases (28/33), respiratory involvement followed the onset of IBD (8 of these 28 cases were postcolectomy), and in the remainder, respiratory manifestations predated the IBD. Patterns of involvement included: 1) Airway inflammation, in the form of subglottic stenosis, chronic bronchitis, severe chronic bronchial suppuration, bronchiectasis, and chronic bronchiolitis. In cases with large airway involvement, endoscopy showed exuberant inflammatory tissue in the airways and narrowing of tracheal and/or bronchial lumen. Histologically, airways were heavily infiltrated by a dense aggregate of inflammatory cells, and there were mucosal ulcerations. 2) Varied patterns of interstitial lung disease, mainly bronchiolitis obliterans with organizing pneumonia, and pulmonary infiltrates and eosinophilia. (3) Miscellaneous other forms of involvement including striking neutrophilic necrotic parenchymal nodules (corresponding histologically to sterile aggregates of neutrophils), and serositis. Steroids were very effective in the majority of cases. Inhaled steroids were of durable benefit in patients with chronic bronchitis, but less often so in those with chronic bronchial suppuration, bronchiectasis, or chronic bronchiolitis. Steroids administered orally led to marked improvement in patients with interstitial lung disease and necrotic nodules, but lacked effectiveness in several patients with severe airway inflammation or chronic bronchiolitis. Intravenous steroids were required in the initial management of life-threatening complications such as asphyxiating subglottic stenosis or extensive interstitial lung disease. Bronchial lavages with methylprednisolone were effective in some patients with severe airway inflammation. Patients with IBD can develop varied inflammatory complications in the lung, and a sizable fraction of these complications is steroid-sensitive. PMID- 8502169 TI - Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. AB - We describe a series of 45 patients with episodic fever of unknown origin (FUO) who meet the classic criteria for FUO. Recurrent or episodic fever is defined as cyclical fever with seeming remission of the disease and fever-free intervals of at least 2 weeks. The traditional mix of infections, malignancies, and inflammatory diseases (multisystem diseases) represent only 20% of the causes of episodic FUO, in contrast to 60 to 70% in cases of continuous fever. The "miscellaneous" group of patients with episodic FUO is the most numerous and about half of the cases remain undiagnosed. This spectrum of causative diseases resembles the spectrum of so-called "prolonged" FUO, i.e., a feverish illness lasting at least half a year. Follow-up of the undiagnosed cases revealed a good prognosis. Only 1 patient died and only 1 more required continuous treatment with corticosteroids. Seven of the 21 undiagnosed cases required intermittent short term treatment with either nonsteroidal anti-inflammatory drugs or corticosteroids. The remaining 14 seem to be "cured". Diagnosis was frequently based on the clinical course and on exclusion of other diseases. Gastrointestinal investigation was useful, but serologic and immunologic tests yielded only minimal benefit. Ultrasonography, computerized tomographic scans, and gallium scintigraphy were diagnostically useful. Invasive procedures are rarely required, and careful ambulatory follow-up is probably the best approach in cases of unresolved episodic FUO. PMID- 8502170 TI - "Circulating anticoagulants: a study of 40 cases and a review of the literature. 1961.": an update. PMID- 8502171 TI - A continuous, simple and rapid method for the detection, extraction and identification of residual antibacterial agents in meat. AB - Most antibacterial agents produced larger inhibition zones and showed lower detectable concentrations on minimal medium (MM) seeded with Bacillus subtilis than on Mueller-Hinton medium. After simple extraction, using a small amount of acetonitrile, from an agar block inside the inhibitory zone produced by each antibacterial agent, identification was carried out by reverse-phase high performance liquid chromatography (HPLC). It is recommended that for inspection of residues MM is superior as a bioassay medium. The continuous, simple and rapid method described may be useful for routine laboratory testing of residual antimicrobial agents in food. PMID- 8502172 TI - Effect of sodium chloride, pH and organic nutrients on the motility of Vibrio cholerae non-01. AB - Using a simple method of semi-solid agar (0.2%) in U-tubes, the effect of temperature, NaCl, pH and nutrients on the motility of environmental Vibrio cholerae non-01 was elucidated. Under aerobic respiration succinate and pyruvate, which are metabolic intermediates, increased the motility rate, with succinate having the greatest influence. Glucose and benzoic acid reduced the motility rate of most of the strains. Optimum motility was obtained at pH 8.6 and 9.1 in all strains examined. Acidic pH 6.1 and alkaline pH 10.0 reduced motility while the strains showed no growth at pH 4.1. The addition of sodium chloride to the media enhanced motility. The incubation temperature also influenced motility with higher rates recorded at 30 and 37 degrees C than at 25 degrees C. PMID- 8502173 TI - Effects of spermine and spermidine on cell division and wall morphogenesis in Saccharomyces cerevisiae. AB - The effect of polyamines (PA) on the synthesis and deposition of wall constituents in Saccharomyces cerevisiae was investigated. Spermidine (Spd) in various doses was ineffective whereas spermine (Sp) in the same concentrations caused a marked inhibition (25-60%) of cell proliferation accompanied by evident morphogenetic malformations. Sp-treated cells were elongated, grouped in small clusters, and showed malformed septa and aberrant wall thickenings. The PATAg technique revealed that the aberrations consisted of an abnormal accumulation of both reactive materials, like 1,3-beta-glucans, and unstained chitin components. Since 1,3-beta-glucan synthases and chitin synthases are inserted in the plasma membrane, whose anionic sites interacted with the cation groups of Sp, it is assumed that the molecule determines a condition resulting in an unregulated activation of the two enzymes. The fact that Spd, which contains three cationic groups instead of the four contained in Sp, is without effect suggests that a compound must have at least four cation sites in order to affect the cell division and wall morphogenesis of S. cerevisiae. PMID- 8502174 TI - Deoxyribonucleic acid relatedness and phenotypic characteristics of oral Streptococcus milleri strains. AB - Strains of oral Streptococcus milleri group were compared with the type strains of Streptococcus anginosus, S. intermedius, and S. constellatus by DNA-DNA hybridization at 60 degrees C. Of the 29 strains tested, twelve, twelve, and two strains were closely related to S. anginosus ATCC 33397T, S. intermedius ATCC 27335T, and S. constellatus ATCC 27823T, respectively. Generally, the strains classified in the S. anginosus group in DNA homology were non-beta-haemolytic and belonged to API S. milleri II and biotype I (lactose fermenting), whereas the strains of S. constellatus group were beta-haemolytic and belonged to API S. milleri I and biotype II (lactose non-fermenting). The strains of the S. intermedius group were all non-beta-haemolytic and belonged to API S. milleri II and mostly biotype II (lactose fermenting). Furthermore, all except one strain of the S. anginosus group were Lancefield group A/serotype a (A/a), ungroupable/serotype b (-/b), C/c, -/d, -/e, F/f or G/k, whereas those of the S. constellatus group were F/-. The strains of the S. intermedius group were -/g, /h, -/i, -/j, or -/-. PMID- 8502175 TI - Drug resistance and broad geographical distribution of identical R plasmids of Pasteurella piscicida isolated from cultured yellowtail in Japan. AB - An MIC test of 12 chemotherapeutic agents performed on 175 strains of Pasteurella piscicida collected from cultured yellowtail (Seriola quinqueradiata) in different areas of Japan from 1989 to 1991 revealed 152 strains (87%) with resistance to combinations of ampicillin (AP), chloramphenicol (CP), kanamycin (KM), nalidixic acid (NA), sulfamonomethoxine (SA), tetracycline (TC), and/or trimethoprim (TMP). The remaining 23 strains were sensitive to all the drugs tested: AP, cefazolin, CP, florfenicol (FF), furazolidone, KM, NA, novobiocin, SA, streptomycin, TC, and TMP. FF showed the most effective antibacterial activity against P. piscicida with MICs ranging from 0.004 to 0.6 microgram/ml. One hundred and forty-nine of the 152 resistant strains carried transferable R plasmids encoding one of the Cp Km Sa Tc, Km Sa Tc, Km Sa, and Sa resistance. The most common resistance marker of transferable R plasmids identified in P. piscicida was Km Sa Tc. R plasmids encoding three different resistant markers were very similar on the basis of their digestion patterns with restriction endonucleases. There was homology among the DNAs of nine transferable R plasmids selected. Our findings suggest that multiple drug resistant strains of P. piscicida carrying transferable R plasmids with the same DNA structure are common in yellowtail farms and that the R plasmid has been retained within the P. piscicida population without change in their DNA structure according to geography and year. PMID- 8502176 TI - Detection of verocytotoxin from stool and serological testing of patients with diarrhea caused by Escherichia coli O157 : H7. AB - The detection of verocytotoxin (VT) in stool and measurement of antibodies against VT and three antigens (unheated-antigen, LPS, and flagellin) of Escherichia coli O157 : H7 in the serum of patients with diarrhea were examined. Five of 14 inpatients during an outbreak had fecal VT2 in stool taken within 5 days of onset to hospitalization. Among these 5, 3 of them also had fecal VT producing E. coli (VTEC) serotype O157 : H7, whereas the other 2 did not. In the passive hemagglutination (PHA) test with formalinized sheep red blood cells sensitized with three VTEC O157 : H7 antigens, 49 (74.2%) of 66 outbreak patients and 3 of 3 sporadic cases had antibodies against both or one of unheated-antigen and LPS of E. coli O157, but none had antibody against flagellin. In addition, anti-VT2 antibody was demonstrated in serum samples from 15 (94%) of 16 inpatients and 2 (4%) of 50 outpatients in an outbreak by a VT-enzyme-linked immunosorbent assay (VT-ELISA). These results showed that serological assay particularly for antibodies against VT and unheated-antigen or LPS of VTEC O157 may provide a useful tool for diagnosis of infection with VTEC O157. PMID- 8502177 TI - Evidence for interference by immune complexes in the serodiagnosis of cryptococcosis. AB - The latex agglutination test was used to compare cryptococcal antigen titers before and after protease treatment in 19 patients with pulmonary cryptococcosis. Antigen was detected by the LA test in 13 of 33 serum samples before protease treatment, and in an additional 13 samples following treatment. Of 26 antigen positive serum samples, 22 (84.6%) showed an increased antigen titer after protease treatment. Using the cell slide agglutination test, antibody was detected in 3 of 19 cases. In one of these 3, antigen could only be detected after protease treatment. Soluble immune complex was prepared in vitro using anti C. neoformans rabbit antiserum and polysaccharide antigen of C. neoformans, and the effects of immune complexes on the LA test were examined. In this experimental model, soluble immune complexes seemed to be observed in antibody excess region, because the antigen titers were increased after the protease treatment. We concluded that C. neoformans capsular polysaccharide antigen and anti-C. neoformans antibody formed soluble immune complexes in patients' sera, which interfered with antigen detection by the latex agglutination test without protease treatment. PMID- 8502178 TI - Release of the outer membrane vesicles from Vibrio cholerae and Vibrio parahaemolyticus. AB - We found numerous small vesicles released from the cell by thin sectioning of the plate culture of Vibrio cholerae and V. parahaemolyticus fixed with the freeze substitution technique. From the broth media of exponentially growing bacteria we could collect the vesicles by the centrifugation but not enough without fixation. The vesicles are encompassed with a membrane structure similar to the outer membrane of these bacteria. The anti-O (Inaba) serum reacted with the surface of the vesicles and the inside of the vesicle are generally filled with an electron dense mass. PMID- 8502179 TI - Antigenic behaviors of two axial flagellar proteins detected in Treponema denticola. AB - Two polypeptide antigens with molecular sizes of 34,000 daltons (34 kDa) and 38 kDa were separated from heated cells of a human clinical treponeme strain G7201 and Treponema denticola ATCC 35404, respectively. The rabbit polyclonal antisera against these antigens were produced and examined for their immunological reactions with the two heated antigens or intact spirochetal cells. Immunoblot analysis showed that the 34-kDa protein was also detected in T. denticola ATCC 35404 and ATCC 33520, and the 38-kDa protein was detected only in the two ATCC strains. Immunoelectron microscopy using the two rabbit antisera and protein A gold complexes demonstrated that the 38-kDa protein antigen was present on the axial flagella of two T. denticola strains, and that the 34-kDa protein was located in the axial flagella of the G7201 cell, but neither in axial flagella nor on outer envelopes of the two ATCC strains cells, suggesting that the native 34-kDa axial flagellar protein of the G7201 strain may be different from that of T. denticola in terms of immunological reactivity. PMID- 8502180 TI - Rickettsia japonica, the etiologic agent of Oriental spotted fever. PMID- 8502181 TI - [Activities of microorganisms isolated from clinical material from dermatophytoses]. AB - Hundred and nine dermatophytes, 14 yeast, 3 bacteria, 11 saprophyte mold were isolated from hair, skin and nail examples of 225 cases. Among isolated dermatophytes, T. rubrum and among yeast species, C. albicans are dominant. PMID- 8502182 TI - [Hepatitis b seroprevalence in hospital personnel]. AB - To investigate the epidemiology of viral hepatitis B (VHB) infection in Ondokuz Mayis University Hospital staff sera of 243 workers and 100 blood donors examined for HBsAg and Anti-HBs with ELISA. The prevalences of HBsAg and Anti-HBs among the workers were 8.6% and 33.7% and among the blood donors were 5 and 24%, respectively. The overall prevalence of donors was 29%. The risk of infection showed a correlation with age and working period but there was no difference according to the jobs and departments. According to these results hospital staff have a great risk for VHB and should be vaccinated for protection from the infection. PMID- 8502183 TI - [Chlamydia trachomatis in conjunctival specimens]. AB - One hundred two patients with signs and symptoms of conjunctivitis and 45 asymptomatic subjects were screened for Chlamydia trachomatis using a direct fluorescent antibody test. 26.5% of the symptomatic and 6.6% of the asymptomatic patients were positive for C.trachomatis. The follicular response rate was significantly higher (p < 0.05) in the symptomatic group than in the asymptomatic population (48.1% and 29.3% respectively). This finding correlated well with chlamydial conjunctivitis. PMID- 8502184 TI - [A case of chronic actinomycosis in a carcinomatous lesion]. AB - A gram positive, catalase-positive Actinomyces viscosus strain has been isolated from cervicofascial carcinomatous lesion. Identification of this human strain of Actinomyces viscosus was carried out with biochemical tests. Tests for catalase, indole, nitrate reduction, methyl red reaction acetoin (VP) and gelatin hydrolysis were done by the procedure recommended by the technique described by Grencser and Slack. Carbohydrate fermentation tests were done with three basal media: Actinomyces fermentation broth, a thioglycolate fermentation base and a brain-heart infusion broth. PMID- 8502185 TI - [Legionnaires' disease following kidney transplantation]. AB - Legionella pneumonia was diagnosed in two patients receiving triple immunosuppressive drug therapy after renal transplantation. High fever was the predominant symptom of these patients. Hyponatremia, leucopenia and anemia were also observed. The disease was diagnosed by immunofluorescence antigen technique and easily controlled with erythromycin therapy. PMID- 8502186 TI - [The transfer of hepatitis B virus (HBV) from HBsAg(+) mothers to their babies]. AB - In this study, Hepatitis B surface antigen (HBsAg) was detected in 3.1% (19/602) of mothers just after delivery. HBsAg positivity was detected in 31% (6/19) in cord blood of newborn infants born from HBsAg positive mothers. Six months later, 15 of the HBsAg positive mothers and their children were screened serologically. HBsAg positivity persisted in only one child (1/15, 6.6%). PMID- 8502187 TI - [In vitro sensitivity of Actinobacillus actinomycetemcomitans to various antibiotics]. AB - In this study, 7 strains of Actinobacillus actinomycetemcomitans (A.a.) were isolated from Localized juvenile periodontitis (LJP) patients and antibiotic susceptibility test by disc diffusion method was utilized. The purpose of this study is to find out the most useful antibiotic against A.a. which is the most important microbial agent in LJP. All seven strains of A.a. were found susceptible to tetracycline, doxycycline, erythromycin, ciprofloxacin and cefuroxime. Two strains were found intermediate susceptible to cephradine. One strain was found resistant to penicillin and another one was found resistant to ampicillin. PMID- 8502188 TI - [Antibacterial and cytotoxic effects of N-butyl-2-cyanoacrylate used as a tissue adhesive]. AB - In this study, the antibacterial and cytotoxic effects of a synthetic tissue adhesive called n-butyl-2-cyanoacrylate (Histoacryl) which provide rapid healing in incision in oral surgical procedures were investigated. The antibacterial effects of Histoacryl were tested by using standard reference strains of Streptococcus pyogenes, Streptococcus mitis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus grown in Mueller-Hinton media (sheep blood supplemented Mueller-Hinton for streptococcus strains) by diffusion technique. The cytotoxic effects were also researched on continuous Vero and primary gingival fibroblast cell cultures by using agar overlay method. In these methods, the inhibition zones produced by Histoacryl were evaluated. As a result, Histoacryl was found to have antibacterial effect on the tested bacteria and produce cytotoxic and cytopathic effects on the tested cell cultures. PMID- 8502189 TI - [Superantigens and antigen recognition of T lymphocytes]. AB - Superantigens are antigens which can stimulate T cells bound to MHC molecules. The conventional foreign antigens are recognized by the T cell within the MHC peptide binding groove. Superantigens differ from conventional antigens. They bind with high affinity to class II MHC molecules outside the antigen binding groove in the absence of antigen processing. The MHC class II/superantigen complexes on antigen presenting cells trigger the proliferation of T cells expressing the TcR-VB gene products. Superantigens can amplify or suppress immune responses. To date, two main groups of superantigens have been described, namely endogenous and exogenous superantigens. Exogenous superantigens are microbial toxins and other protein products. Endogenous superantigens are the products of unlinked genetic loci in mice the best known of which are the murine retroviral gene products. Toxins of S. aureus and S. pyogenes are the best known exogenous superantigens, implicated in Toxic Shock Syndrome. PMID- 8502190 TI - [Hospital infections and the role of the microbiology laboratory in hospital infection control]. PMID- 8502191 TI - Potential use of IgA protease therapy in IgA myeloma patients. AB - Multiple myeloma is generally not cured with conventional cytotoxic chemotherapy. Biologic agents and bone marrow transplantation have been among the newer avenues explored to increase the cure rate. It is suggested that IgA proteases too may be of value in the treatment of IgA myeloma. PMID- 8502192 TI - Looking for a 'superantigen' in AIDS: a possible role for Mycoplasma? AB - The extensive effort made to comprehend the complex immunopathology of human immunodeficiency virus (HIV) infection has resulted in research groups focusing attention on hypotheses as disparate as the possible 'superantigen' potential of HIV and the possible requirement for a Mycoplasma 'cofactor'. Utilizing the recent observation that a Mycoplasma species possesses 'superantigen' properties, this paper attempts to reconcile these seemingly discrepant observations in a model of the acquired immunodeficiency syndrome (AIDS) which builds on the potential contribution of a 'superantigen cofactor' to the ongoing process of HIV infection. A possible role for mycoplasma-induced T-cell proliferation, T-cell dysfunction, B-cell proliferation, and hyperglobulinaemia in the exacerbation of HIV infection is discussed. The relevance of a recent observation regarding protein sequence homology between the mycoplasma adhesion protein and several human class II major histocompatibility complex (MHC) proteins is also examined and incorporated into this model. PMID- 8502193 TI - Acanthosis nigricans--decreased extracellular matrix viscosity: cancer, obesity, diabetes, corticosteroids, somatotrophin. AB - Acanthosis nigricans is a reaction pattern to over a dozen different causes. The skin, most classic in the axilla, is dark, soft, velvet-like with fine folding and papillae. The mechanism of this skin change is decreased viscosity of extracellular matrix (ECM) combined with mechanical extrusion of ECM into papillae extending out from the upper dermis. It occurs in obesity (increased mechanical pressure on ECM), diabetes (decreased quality of glycosaminoglycans) (GAG), excess corticosteroids (decreased quality of GAG), pineal tumors (increased ECM and edema), other endocrine disorders (alterations in the quality of GAG), multiple genetic variants (structural and chemical change), from drugs such as nicotinic acid, estrogens, corticosteroids (weakened or altered GAG) and adenocarcinoma (fractions of depolymerized or altered GAG released from the tumor area are incorporated into and weaken the skin GAG). Acanthosis nigricans was first reported in 1890 as a cutaneous sign of internal malignancy. Acanthosis nigricans presents an opportunity to better understand what is occurring in the ECM in many disorders. The understanding of the association of AN and internal malignancy will expand our understanding of how a neoplasm decreases generalized ECM viscosity. PMID- 8502194 TI - The photo-biochemical basis of infant colic: pineal intracellular calcium concentrations controlled by light, melatonin, and serotonin. AB - Infant crying during the first 3 months of life exhibits a circadian rhythm with peak crying in the evening hours. Intracellular calcium ion within the pineal gland may be influenced by alternating light and dark, melatonin concentrations, and serotonin concentrations which both exhibit circadian rhythmicity. Differences in light by latitude and differences in the ontogenic development of melatonin and serotonin rhythmicity could combine to effect the pineal intracellular concentrations of calcium and result in high levels of infant crying called colic. PMID- 8502195 TI - Dyspermia in men with localized Hodgkin's disease. A potentially reversible, immune-mediated disorder. AB - Localized Hodgkin's disease (HD) is curable in the great majority of patients. However, common programs of chemotherapy for this disease render most men permanently azoospermic. In studies of seminal cryopreservation prior to treatment, it has been recognized that many men with HD are dyspermic at diagnosis. It is hypothesized that this abnormality reflects a change in the cellular regulation of spermatogenesis; specifically an alteration in the balance between distinct sub-populations of lymphocytes which normally either inhibit or stimulate the production of sperm. This change in regulation within the testes is believed to be part of a systemic perturbation which is unrelated to the extent of HD but is potentially reversible with effective treatment of the primary disease. Recognizing the distinction between sperm analyses and fertility status, it is proposed that radiotherapy of localized HD, delivered in a manner that is not toxic to the male gonad, will restore useful spermatogenesis in patients who are dyspermic (and probably subfertile) before treatment is initiated. PMID- 8502196 TI - The cardiomyopathy of Duchenne's muscular dystrophy and the function of dystrophin. AB - Duchenne's muscular dystrophy (DMD) is a common X-linked neuromuscular disease which predominantly affects skeletal and cardiac muscle. The absence of dystrophin, the metabolic defect that causes DMD, leads to a peculiar cardiomyopathy which initially affects the posterior wall of the left ventricle. We review evidence that dystrophin deficient myocytes become dystrophic in order of increasing axial stress upon the myocyte. Thus, dystrophin's function may be that of physically reinforcing the sarcolemma against the axial forces exerted upon the myocyte. PMID- 8502197 TI - Mechanisms of glycation in atherogenesis. AB - Non-enzymatic glycation may affect the arterial wall altering its connective tissue and promoting LDL accumulation. Its recognition by specific receptors and growth factor release, as well as possible alteration of DNA, may stimulate smooth muscle cell proliferation. Free radical generation may favour non enzymatic PUFA degradation and quench NO, which would alter vascular relaxation. All of these aspects may participate in atherogenesis. PMID- 8502198 TI - Zinc in etiology of periodontal disease. AB - Microbial plaque is the main etiological factor of periodontal disease. The bacterial polysaccharides stimulate gingival neutrophils and macrophages to interleukin-1 (IL-1) production. IL-1 causes a complex of redistribution processes with liver as the central organ. Accumulation of zinc in liver and their copper and ceruloplasmin production also elicits increase of copper and decrease of zinc in gingiva. The elevated level of copper in connection with zinc deficiency in gingiva causes the increase of permeability of gingival epithelium for bacteria. The stimulated inflammatory infiltrate produces more IL-1 and the vicious circle is complete. PMID- 8502199 TI - Coronary artery spasm and no spasmogens? AB - Traditionally coronary artery spasm, which is implicated in the pathogenesis of angina, myocardial infarction and sudden death, has been perceived as involving either a powerful spasmogen or larger quantities of a less potent stimulant. The present essay proposes that spasm may occur in the complete absence of any inciting chemical or spasmogen. Sudden intense coronary artery constriction may reflect an abnormality in an intrinsic system of tone regulation involving pacemaker cell discharge, intercellular conduction through gap junctions to adjacent cells, and the cycling of extracellular and bound calcium. Defects in spontaneous tone generation and recovery, may be primary factors in the causation of clinically occurring coronary artery spasm and its sequela. PMID- 8502200 TI - Informed opinion: an exercise in gathering the opinions of experts to facilitate the planning of continuing professional education. AB - In 1989 The English National Board for Nursing Midwifery and Health Visiting reviewed the organisation and provision of continuing professional education in order to identify a new structure which would meet most effectively the changing health care needs of clients and patients. Researchers were engaged in conducting a series of projects looking at key areas of concern in continuing professional education. During the research concern was expressed about levels of practice and preparation for practice. Respondents suggested that practitioners make highly complex decisions for which there is no apparent continuing education preparation. The research director decided that this issue should be explored further by selected individuals from the research team. This paper describes one of the approaches used to explore this area. Using the work of Benner (1984) as a framework for debate during three 1-day workshops, a panel of experts in nursing education and practice explored skill acquisition and attainment of expert clinical practice and considered these in relation to potential continuing educational development strategies for nursing, midwifery and health visiting. The conclusions drawn from this exercise were then 'fed' back to the research team. This paper examines the process of utilising experts in facilitating planning. PMID- 8502201 TI - The need for substance misuse education in health studies curriculum: a case for nursing education. AB - The sharp increase, in recent years, in the use and misuse of psychoactive substances necessitates greater involvement of non-specialist health care workers in the management of problems associated with substance misuse. The need to expand the health studies curriculum in line with current trends in substance use and misuse is recommended. PMID- 8502202 TI - Accounting for power: nurse teachers' and students' perceptions of power in their relationship. AB - In this paper I examine how nurse teachers and students perceive power to operate within their relationship. Interviews and focus group discussions showed that teachers and their students agreed that power operates within three distinct planes: the educational process, interpersonal relationships and learning outcomes. Common perceptions of power distributions within these planes were also demonstrated. A major difference was found to be in the emphasis accorded to power planes. Teachers related more to educational power while students were more concerned with personal power. I suggest how the findings can be applied to resolve seemingly conflicting teacher/student perceptions of power distribution and discuss how students believe they can best be empowered by teachers. PMID- 8502203 TI - Unique theory--is it essential in the development of a science of nursing? AB - This paper is concerned with the struggle to develop unique theories of nursing and their contribution to clinical practice and the nursing profession. The nature of nursing is briefly discussed and the knowledge base explored. It is argued that nursing knowledge is not unique, but the perspective with which the knowledge is applied to practice is unique. This perspective is achieved and defined through unique theories of nursing. The value and contribution of nursing theories in Britain to date is then questioned and critically discussed, with arguments made to show that nursing theory has at times been more concerned with achieving a higher professional status, than with the advancement of clinical practice. The paper concludes with a discussion on the need for theories which define and value all aspects of the art and the science of nursing practice, and are both useful and acceptable to practitioners. PMID- 8502204 TI - Current issues in choosing personal computers. AB - This paper offers a discussion of the main considerations that nurse educators need to make when choosing a personal computer for their own use. Whilst the issues under discussion are targeted at the home user, those same issues are also relevant to the corporate buyer or the manager who is budgeting for a department or college. The paper highlights issues concerning Central Processing Units (CPUs), keyboards and monitors and identifies some of the software applications that are available. PMID- 8502205 TI - The use of music in curriculum evaluation. AB - This article outlines the importance of curriculum evaluation and discusses some reasons for it. In particular, it is concerned with the role of reflection. The article further examines how music can be used as an aid to evaluate a course. PMID- 8502206 TI - The reluctant participant in experiential learning. AB - Experiential learning methods are increasingly being used in nurse education, particularly in the field of interpersonal skills training. One basic tenet of experiential learning is that participation in such learning should always be voluntary. This tenet raises issues for nurse teachers committed to this approach who come upon a student who persistently opts out of taking part in experiential exercises, leading sometimes to indirect attempts to coerce students into participating. This paper examines these issues in the light of evidence as to the effectiveness of experiential learning methods. It concludes that attempts to coerce students into participation can never be justified, but non-participation should be minimised if the teacher employs good practice in conducting experiential learning. PMID- 8502207 TI - Reducing the threat: an experiential exercise to introduce role play to student nurses. AB - Role play is regarded as being a useful learning method for assisting student nurses to improve their interpersonal skills. It can provoke strong feelings in students both for and against its use, and the participation rate in role play exercises tends to be low. This paper describes an experiential exercise designed to introduce the concept of role play to students in a way that is hopefully less threatening than role play 'proper', with the aims of encouraging students to discuss the issues around the use of role play, and to reach a decision as to whether they will participate in role play in the future, and on what terms. It is hoped that the opt-out rate from role playing will be reduced, through students becoming more familiar with the method. PMID- 8502209 TI - Preparing nurses for their role in management. PMID- 8502208 TI - Towards a theory of student-centred nurse education: overcoming the constraints of a professional curriculum. AB - Student-centred learning is an educational philosophy which became popular during the 1960s, but which has gradually fallen from favour as the educational and political climate has changed over the years. This is particularly true of nursing, where the transition to higher education ushered in by Project 2000 has signalled a return to traditional teaching methods such as the lecture and the seminar. This paper argues that the current demands for holistic practice, professional autonomy and primary nursing can best be met by educationalists by employing a student-centred approach to learning. However, it is recognised that a radical student-centred approach will conflict with the constraints imposed on curriculum writers by a professional body, and that a modified strategy is required. The paper goes on to identify several of the more pressing constraints, and suggests some methods for overcoming these problems within a student-centred framework, while maintaining the requirements of a professional training which confers upon the students a license to practise. The paper concludes by suggesting that most problems will only be identified once courses are up and running, and that a new student-centred framework can only emerge from educational practice. Teachers and curriculum writers are therefore encouraged to come together to share ideas and experiences in order to carry forward the theory and practice of student-centred nurse education. PMID- 8502210 TI - Assessment of competence in clinical practice--a review of the literature. AB - Continuous practical assessments for those programmes leading to registration began to be introduced in the UK in the late 1970s and were generally hailed, certainly by educationalists, as being a much more valid, reliable and realistic method of assessment (Quinn 1989). However, now, with the increasing pressures on the role of the ward manager, the introduction of supernumerary status for learner nurses and shorter clinical placements, it could be argued that continuous practical assessment is in great danger of becoming no assessment at all. The extent to which experienced nurses are able to supervise and give the continued feedback on learners' progress that was considered such a significant improvement on the previous systems of assessments is questioned. On examination of the literature, consideration will be given to how experienced nurses measure and help others measure performance. The tools practitioners use to assist them in forming their judgements need to be examined. Are practitioners concerned with students' successful completion of tasks or do they rely on intuitive judgements in the complexity of the 'real life' situation? If intuitive judgements are involved, do they have any foundations, or are they concerned with mere random form completion and personality measures? In particular examination will be made of the various measurement tools available and different approaches to the assessment of competency in the 'real world' of nursing practice. Since the United Kingdom Central Council (UKCC) formally introduced the Nurses' Rules (Nurses, Midwives and Health Visitors Act 1979) in 1983, all courses throughout the UK, leading to registration had to begin to formally prepare students to work towards the achievement of the identified competencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502211 TI - A multifactorial study of test anxiety and coping responses during a challenge examination. AB - Challenge examinations offer registered nurse students enrolled in our baccalaureate nursing programme the opportunity to demonstrate mastery of course content through a testing process. Successful students receive credit for the course while those who are unsuccessful must take the course to proceed in the programme. Faculty observations of registered nurse students during the challenge process suggested this testing was stressful. Therefore, a study was conducted to determine anxiety levels and coping strategies of on-campus and distance education registered nurse students at three different times during the challenge examination process. Differences between the two groups of nursing students on selected demographic variables, past academic performance, anxiety levels and coping strategies were assessed from the perspective of Folkman & Lazarus's (1984) theory of stress and coping. Significant differences were found in anxiety levels, coping strategies and past academic performance by age, marital status, employment and work setting. Several different coping strategies were used. However, problem solving was used extensively by both groups while social support was used more by the on-campus students. The results are discussed in terms of Folkman & Lazarus's theory of stress and coping, and implications for nurse educators are presented. PMID- 8502212 TI - Recommended infection-control practices for dentistry, 1993. Centers for Disease Control and Prevention. AB - This document updates previously published CDC recommendations for infection control practices in dentistry to reflect new data, materials, technology, and equipment. When implemented, these recommendations should reduce the risk of disease transmission in the dental environment, from patient to dental health care worker (DHCW), from DHCW to patient, and from patient to patient. Based on principles of infection control, the document delineates specific recommendations related to vaccination of DHCWs; protective attire and barrier techniques; handwashing and care of hands; the use and care of sharp instruments and needles; sterilization or disinfection of instruments; cleaning and disinfection of the dental unit and environmental surfaces; disinfection and the dental laboratory; use and care of handpieces, antiretraction valves, and other intraoral dental devices attached to air and water lines of dental units; single-use disposable instruments; the handling of biopsy specimens; use of extracted teeth in dental educational settings; disposal of waste materials; and implementation of recommendations. PMID- 8502213 TI - Outbreak of acute illness--southwestern United States, 1993. AB - Beginning in May 1993, cases of acute illness characterized by fever, myalgias, headache, and cough, followed by rapid development of respiratory failure, have been reported to the New Mexico Department of Health (NMDOH), Arizona Department of Health Services (ADHS), Colorado Department of Health (CDH), and Utah Department of Health (UDH). This report presents preliminary findings from an ongoing investigation of this problem, which suggest this illness is associated with a previously unrecognized hantavirus. PMID- 8502214 TI - Selective screening to augment syphilis case-finding--Dallas, 1991. AB - Increased use of crack cocaine and the exchange of sex for drugs have been major contributors to the increased occurrence of syphilis in U.S. urban, minority populations (1-3). Because many persons who use drugs do not voluntarily seek health care (1,4), and because their sex partners are often difficult to locate (5), a substantial number of persons may have undiagnosed syphilis infections, thereby contributing to continuing transmission. Because of the continuing increase in the number of persons in Dallas County (1990 population: 1.8 million), Texas, in whom early syphilis* had been diagnosed, and who had reported having had sex partners at crack motels and crack houses (i.e., places where crack cocaine was sold), in February 1991, the Dallas Countywide Health Department (DCHD) developed a sexually transmitted disease (STD) screening program aimed specifically at those sites. This report describes Dallas County's selective screening program and summarizes results of the program from March 1 through December 31, 1991. PMID- 8502215 TI - Outbreak of multidrug-resistant tuberculosis at a hospital--New York City, 1991. AB - From January 1991 through July 1992, multidrug-resistant (i.e., resistant to at least isoniazid [INH] and rifampin [RIF]) Mycobacterium tuberculosis (MDR-TB) was isolated from 43 (22%) of 198 patients with newly diagnosed TB at a New York City hospital. This report summarizes an epidemiologic investigation by the hospital infection-control, infectious diseases, and employee services staffs and presents information for the 32 patients in whom MDR-TB was diagnosed during January 1991 March 1992 (these were the only patients for whom complete information was available and analyzed). PMID- 8502216 TI - Comprehensive assessment of health needs 2 months after Hurricane Andrew--Dade County, Florida, 1992. AB - On August 24, 1992, Hurricane Andrew struck southern Florida. More than 28,000 houses, mobile homes, and apartment buildings were destroyed, and approximately 107,000 additional dwellings sustained major damage. An estimated 180,000 persons were left homeless; insured damages were estimated at $15.5 billion and total damages at more than $30 billion. During the recovery period, many private and public health-care facilities damaged or destroyed in the storm were not functional. During November 3-13, to help prioritize health needs and direct public health resources, the Dade County Public Health Unit of the Florida Department of Health and Rehabilitative Services conducted a survey to assess health needs and the availability of health-care services during the recovery phase with funds provided by the Federal Emergency Management Agency (FEMA). This report summarizes the results of the survey. PMID- 8502217 TI - Adult Blood Lead Epidemiology and Surveillance--United States, first quarter, 1993. PMID- 8502218 TI - Update: outbreak of hantavirus infection--southwestern United States, 1993. AB - Since May 1993, the New Mexico Department of Health, the Arizona Department of Health Services, the Colorado Department of Health, the Utah Department of Health, the Indian Health Service (IHS), and CDC, with the assistance of the Navajo Nation Division of Health, have been investigating an outbreak of acute illness characterized by a prodrome most commonly including fever, myalgias, headache, and cough, followed rapidly by respiratory failure. Preliminary laboratory findings have suggested this outbreak is associated with infection with a hantavirus or a closely related agent. This report updates the ongoing investigation of this outbreak. PMID- 8502219 TI - Economic impact of motor-vehicle crashes--United States, 1990. AB - Injuries resulting from motor-vehicle crashes are the leading cause of death for persons of every age from 6 through 33 years and have a large economic impact on the general population. This report summarizes an analysis by the National Highway Traffic Safety Administration (NHTSA) of costs for total and alcohol related motor-vehicle crashes during 1990 and estimates the economic impact for police-reported and unreported crashes. PMID- 8502220 TI - HIV prevention through case management for HIV-infected persons--selected sites, United States, 1989-1992. AB - Transmission of human immunodeficiency virus (HIV) infection can be prevented through HIV-prevention case management--a one-on-one client service specifically designed to assist HIV-infected persons in receiving services that will prevent or reduce behaviors that result in further spread of the virus, delay the onset of symptomatic HIV disease, and improve the client's health status. This approach enables HIV-infected persons to enter a stable, ongoing medical-care system and supports prevention goals by providing multiple opportunities to provide risk reduction information and to reinforce safer behaviors. This report summarizes an assessment of HIV-prevention case-management systems in three community health centers (CHCs) during 1989-1992 and provides information regarding self-reported changes in sexual risk behaviors of HIV-seropositive clients. PMID- 8502221 TI - Mortality trends and leading causes of death among adolescents and young adults- United States, 1979-1988. AB - Approximately three fourths of the more than 40,000 deaths each year among persons aged 10-24 years in the United States are related to preventable causes such as motor-vehicle crashes (37%), homicide (14%), suicide (12%), and other injuries (e.g., drowning, poisoning, and burns) (12%). To characterize changes in leading causes of death among adolescents and young adults during 1979-1988, data were analyzed from the vital statistics mortality reporting system maintained by CDC's National Center for Health Statistics. This report summarizes the results of the analysis. PMID- 8502222 TI - Quarterly table reporting alcohol involvement in fatal motor-vehicle crashes. PMID- 8502223 TI - Isolation and expression of a cDNA coding for rat kidney cytosolic cysteine conjugate beta-lyase. AB - The role of rat kidney cysteine conjugate beta-lyase in the production of nephrotoxic thiols from S-cysteine conjugates of xenobiotics has been well established. However, the factors controlling the cellular distribution and substrate specificity of the enzyme have yet to be elucidated. As an approach to this we have isolated a cDNA for cysteine conjugate beta-lyase from a rat kidney cDNA library, using a combination of immunological and hybridization screening. A full length cDNA was sequenced and its identity was confirmed by deduced molecular weight, deduced amino acid composition, the presence of a consensus pyridoxal phosphate (PLP) binding site in the deduced amino acid sequence, kidney specific expression of the corresponding mRNA, and the expression of beta-lyase and glutamine transaminase K activities in tissue culture cells transfected with the cDNA. The cDNA coded for a protein of 48 kDa containing the sequence Ser-Ala Gly-Lys-Ser-Phe, which corresponds closely to the PLP binding site in other PLP containing enzymes. Use of the cDNA to detect beta-lyase mRNA sequences in rat liver and kidney RNA demonstrated that expression was kidney specific and that the mRNA size (2.1 kilobases) was in good agreement with the size of the cDNA. When the cDNA was inserted into the expression vector pUS1000 and transfected into COS-1 tissue culture cells, a 7-10-fold increase in cytosolic beta-lyase and glutamine transaminase K activities could be detected. The use of beta-lyase cDNA for the elucidation of the mechanism of action of this enzyme and for the development of in vitro systems to examine xenobiotic cysteine conjugate toxicity is discussed. PMID- 8502224 TI - Development of polyclonal anti-D2 dopamine receptor antibodies using sequence specific peptides. AB - Multiple subtypes of dopamine receptors with similar properties have been described. Ligands that have been shown to interact with a single subtype of receptor do not yet exist. The use of immunologic methods provides an alternative approach to distinguish receptors and receptor isoforms. Synthetic peptides corresponding to portions of the third intracellular loops of the two isoforms of the rat D2 dopamine receptor were used to elicit polyclonal antipeptide antibodies. Peptide D2-244 is unique to the D2L isoform, whereas peptide D2-284 is present in both the D2L and the D2S isoforms. Rabbits were immunized monthly with peptide coupled to keyhole limpet hemocyanin. The immunogenicity of the peptides was established using a solid-phase radioimmunoassay. Both immunogens elicited antipeptide antibodies within 10 weeks of the primary immunization, with titers of at least 1/10(4). An immunoprecipitation assay using receptors in digitonin-solubilized extracts of rat or canine caudate labeled with the high affinity D2 antagonist 125I-NCQ 298 showed that antipeptide antisera could recognize solubilized D2 receptors. At a dilution of 1/1000, antisera to peptide D2-284 quantitatively immunoprecipitated 125I-NCQ 298 binding sites from both rat and canine striatal tissue, whereas antisera against peptide D2-244 immunoprecipitated 40% of the D2 receptors solubilized from rat caudate. The selectivity of the antisera was determined using 293 cells transfected with cDNA encoding the D2L or the D2S isoform of receptor. Antisera to D2-284, at a dilution of 1/1000, were able to quantitatively immunoprecipitate receptor from both 293-D2L and 293-D2S cells. Antisera to D2-244 were specific for the D2L isoform, immunoprecipitating 125I-NCQ 298 binding sites from 293-D2L cells but not from 293-D2S cells. Anti-D2-284 specifically recognized multiple bands of 100 kDa, 68 kDa, and 50 kDa in immunoblots of denatured preparations of rat caudate. Immunohistochemical studies with anti-D2-284 demonstrated the presence of the D2 receptor in several regions of rat brain. Immunostaining was most dense in the striatum, with a lateral to medial gradient and patches of lighter staining. Immunoreactivity was negligible with preimmune serum or peptide-blocked immune serum. Immunoreactive processes were seen in the nucleus accumbens and ventral pallidum, as well as in the hypothalamus. The high affinity binding of agonist to D2 dopamine receptors was disrupted by anti-D2-284 but not anti-D2-244 antisera, implicating the internal region of the third intracellular loop represented by peptide D2-284 as a potential determinant of receptor-guanine nucleotide-binding protein coupling. PMID- 8502225 TI - Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium. AB - Angiotensin II (AII) binding sites were characterized in human myometrium membrane preparations. The sites were saturable and of high affinity (Kd of 0.09 nM and Bmax of about 200 fmol/mg of protein). PD 123319 completely inhibited 125I AII binding, with an IC50 of 30 nM, whereas L-158,809 (1 microM) had no significant effect on 125I-AII binding. These results indicate that human myometrium contains almost exclusively the AT2 receptor subtype. Association and dissociation studies performed with 125I-AII on human myometrium membranes revealed that AII had a very high affinity for AT2 receptors, with a Kd of 0.01 nM (association rate constant K1 = 1.056 x 10(12) mol-1 min-1; dissociation rate constant K2 = 0.003 min-1). The photoactivable AII analogue [Sar1, Val5, D Phe8(N3)]AII displayed a high affinity for AT2 receptors (IC50 of 0.18 nM), but its radioiodinated form showed poor efficiency in photoaffinity labeling experiments. A newly synthesized photoactivatable analogue of AII, [Sar1, p benzoyl-Phe8]AII, (AII-Bpa), also displayed a high affinity for AT2 receptors of human myometrium (IC50 of 0.3 nM). Photoaffinity labeling experiments were performed with 125I-AII-Bpa, and a high yield (70%) of covalent incorporation to human myometrium membranes was obtained upon photolysis. Covalently labeled receptors were solubilized, denatured, and subjected to polyacrylamide gel electrophoresis. Autoradiography of the polyacrylamide gel revealed a single band, of 68 kDa, and the labeling of this band was completely abolished in the presence of 1 microM PD 123319, indicating selective labeling of the AT2 receptor subtype. These results demonstrate that AII-Bpa is a very efficient tool for selective photoaffinity labeling of the AT2 receptor. PMID- 8502226 TI - Differential regulation of muscarinic receptor mRNA levels in neuroblastoma cells by chronic agonist exposure: a comparative polymerase chain reaction study. AB - The human neuroblastoma line SH-SY5Y expresses three muscarinic receptor genes (m1, m2, and m3). In this study, we have investigated the effect of agonist exposure on the steady state levels of each muscarinic receptor transcript, using a comparative polymerase chain reaction (PCR) assay that allows changes in levels of very rare transcripts to be monitored. Northern blot analysis of cellular RNA revealed the presence of m3 mRNA, whereas PCR amplification of SH-SY5Y cDNA additionally revealed the presence of m1 and m2 transcripts. Cell surface muscarinic receptor number, as assessed by N-[3H]methylscopolamine binding to whole cells, rapidly decreased to 42% of control levels within 1 hr of exposure to 100 microM carbachol; this was followed by a slower decline to 6% of control levels after 48 hr. Total receptor number, measured by binding of [3H]quinuclidinyl benzilate, showed a much slower decline to 21% of control levels after 48 hr of treatment. Comparative PCR analysis showed that each muscarinic transcript was differentially regulated. The level of transcript encoding the major receptor population, the m3 mRNA, was rapidly elevated within 1 hr of agonist challenge and subsequently decreased to about 30% of prestimulation levels within 9 hr; this decrease was sustained for the time course of the experiment. m2 mRNA levels showed a transient increase followed by a decrease to 30% of prestimulation levels after 6 hr but, in contrast to the m3 transcripts, this depression was followed by a transient rise to 270% of prestimulation levels after 24 hr before declining to normal levels by 72 hr after stimulation. Exposure of cells to agonist clearly instigates a complex pattern of changes in levels of receptor and receptor mRNA; comparison of the relative time courses of these changes indicates that the decline in m3 transcripts precedes the loss of muscarinic receptor binding sites. PMID- 8502227 TI - Variation in human thymidylate synthase is associated with resistance to 5-fluoro 2'-deoxyuridine. AB - Two human colorectal tumor cell lines are differentially sensitive to growth inhibition by 5-fluorodeoxyuridine (FdUrd); cell line RCA is less sensitive to FdUrd than is cell line C. Thymidylate synthase (TS), a target of FdUrd, has been purified to homogeneity from both cell lines. Because of differences in the avidity for a folate ligand affinity matrix, TS forms from the cells were purified by two different procedures. Relative to the enzyme from C cells, the enzyme from RCA cells demonstrated higher Km values for the substrates deoxyuridylate and 5,10-methylene-tetrahydrofolate, a lower rate of association of the inhibitor 5-fluorodeoxyuridylate (FdUMP), a similar rate of FdUMP dissociation, and lower enhancement of covalent FdUMP binding by folate derivatives. The activities of the enzymes in situ and the catalytic efficiencies of the purified enzymes were similar. Thus, a cell line that is naturally resistant to FdUrd has been identified that expresses a TS with reduced affinity for FdUMP and 5,10-methylenetetrahydrofolate, relative to the enzyme expressed in a FdUrd-sensitive cell line. PMID- 8502228 TI - Tamoxifen stimulates expression of the c-fos proto-oncogene in rodent uterus. AB - Estrogens regulate the in vivo expression of the c-fos proto-oncogene in rat uterus, and this regulation appears to occur at the transcriptional level. This system thus provides the ability to study the in vivo effects of antiestrogens on specific gene expression in normal estrogen target tissue. Immature rats were treated with estradiol, tamoxifen, or other nonsteroidal antiestrogens, total uterine RNA was isolated, and c-fos transcript levels were monitored by blot analysis. Tamoxifen increases the 2.2-kilobase c-fos transcript approximately 20 fold in 6 hr. This effect is comparable in magnitude to that produced by estradiol, but the maximum response to the hormone occurs in 3 hr. c-fos induction is observed at doses of 0.1-10 mg/kg tamoxifen. The nonsteroidal antiestrogens nafoxidine, Cl-628, and 4-hydroxytamoxifen also induce c-fos expression. The induction of c-fos by both estradiol and tamoxifen is blocked by the progestin medroxyprogesterone acetate. In addition to effects on c-fos mRNA, tamoxifen also increases uterine levels of c-jun, jun-B, and c-myc mRNAs. These results indicate that tamoxifen acts in vivo as an estrogen agonist for activating expression of cellular oncogenes in normal uterine tissue. PMID- 8502229 TI - Marked endogenous activation of the CYP1A1 and CYP1A2 genes in the congenitally jaundiced Gunn rat. AB - The homozygous recessive jaundiced Gunn rat lacks expression of bilirubin UDP glucuronosyltransferase and serves as a model for Crigler-Najjar syndrome type I, in which high and toxic plasma levels of bilirubin result from this genetic defect in bilirubin conjugation. Both rats and humans dispose of this heme waste product by an alternate metabolic route that involves oxidation of the compound, followed by biliary excretion of the more polar metabolites. To determine the role of cytochrome P450 in this process, hepatic levels of cytochrome P450 mRNA and protein were measured in jaundiced and nonjaundiced Gunn rats as a function of age and sex. The mRNA and protein levels of cytochrome P450(CYP) 1A1 and CYP1A2 were markedly elevated in the jaundiced rats at the age of 10 days, compared with their nonjaundiced littermates. Levels of CYP2E1 mRNA and protein did not differ between these rats, indicating that the CYP1A P450 genes were specifically induced. CYP1A1 mRNA and protein levels increased further in the jaundiced animals between 10 days and 1 month of postnatal life but remained undetectable in the nonjaundiced littermates. On the other hand, CYP1A2 mRNA and protein content increased during this time period in both jaundiced and nonjaundiced rats, but at the age of 1 month there were no major differences between the two groups. CYP1A2 mRNA and protein levels were indistinguishable in 3-month-old jaundiced and nonjaundiced Gunn rats, whereas CYP1A1 could not be detected in either group. These data suggest that young jaundiced Gunn rats cope with the degradation of toxic bilirubin by increasing hepatic levels of CYP1A1 and CYP1A2. On the other hand, normal developmental activation of CYP1A2 may provide the alternative pathway for bilirubin degradation in adult animals. This is the first demonstration of the induction of cytochrome P450 gene expression to permit the elimination of an endogenously generated neurotoxic chemical in a genetic disease in which the normal excretory mechanism is impaired. PMID- 8502230 TI - Subsecond modulation of formyl peptide-linked guanine nucleotide-binding proteins by guanosine 5'-O-(3-thio)triphosphate in permeabilized neutrophils. AB - Rapid activation of guanine nucleotide-binding protein (G protein)-mediated signal transduction mechanisms occurs in many tissues. The human neutrophil provides a useful model for studying the mechanisms of these fast processes. Fluorescent chemotactic tetrapeptide and pentapeptide exhibit 30-50% quenching of fluorescence upon binding to the neutrophil formyl peptide receptor, and their binding affinity is strongly regulated by the G protein Gi. We used rapid kinetic spectrofluorometric methods to study the assembly and disassembly of the ternary complex of ligand, receptor, and G protein in digitonin-permeabilized human neutrophils. Binding was studied up to 20 nM ligand, where the half-time for association was 1.2 sec. The rate constant of association was near that for diffusion-limited reactions of ligands and proteins, 2 x 10(7) M-1 sec-1. The rate of uncoupling of formyl peptide receptor from G protein in the presence of high concentrations of guanine nucleotide was > or = 5 sec-1 (i.e., t1/2 of 0.14 sec). Thus, disassembly of the formyl peptide receptor-G protein complex occurs in the millisecond time domain and may be faster than the next step in the signal transduction process. PMID- 8502231 TI - Isolation of glucagon antagonists by random molecular mutagenesis and screening. AB - Glucagon has an important role in the regulation of glucose homeostasis, and glucagon antagonists may be effective therapeutic agents in the control of diabetes mellitus. We were able to identify a number of analogs with antagonist activity by creating libraries of mutant glucagon coding sequences, expressing them in a yeast (Saccharomyces cerevisiae) secretion system, and screening for clones that produce analogs that inhibit the glucagon stimulation of rat hepatocyte membrane adenylate cyclase. These libraries were constructed by allowing random misincorporation during the synthesis of oligonucleotides that contained the complete coding sequence for mammalian glucagon or for an analog (desHis1-glucagon) that had partial antagonist activity. We developed and used a simplified screening assay to test culture broths from > 3500 individual transformant yeast clones for their ability to inhibit glucagon-dependent adenylate cyclase activity. Ultimately, > 20 different analogs with antagonist activity were identified by recovering and sequencing plasmid DNA from yeast strains that were positive in the screening assay. Interestingly, several analogs were identified repeatedly in independent yeast clones and certain amino acid substitutions occurred in more than one analog. This clustering of randomly isolated mutations clearly delineates the regions of the glucagon molecule that are important for designing improved glucagon antagonists. A subset of the antagonists identified in yeast broth were produced by peptide synthesis to confirm their activities as pure compounds. PMID- 8502232 TI - Development of natriuretic peptide analogs selective for the atrial natriuretic factor-R1A receptor subtype. AB - A pharmacological characterization of subtypes of the atrial natriuretic factor (ANF) receptor ANF-R1, found in bovine adrenal cortex and rat papillary membrane preparations, has been carried out using various chimeric analogs based on rat ANF(99-126) [rANF(99-126)] and porcine brain natriuretic peptide 32 (pBNP32). Receptor binding and cGMP production assays in bovine adrenal cortex indicate that replacement of the amino-terminal segment of pBNP32 with that of rANF(99 126) enhances the affinity of the peptide for the ANF-R1A receptor subtype and its stimulation of associated guanylate cyclase activity. In rat kidney papillae, the substitution of amino- and/or carboxyl-terminal portions of pBNP32 with those of rANF(99-126) also results in a large increase in the affinity and agonistic potency for the ANF-R1A subtype but in only modest changes in those for the ANF R1B receptor subtype. Interestingly, in this preparation the chimeric analogs could discriminate by their differential affinities and cGMP production potencies between the two receptor subtypes. In particular, pBNP1, obtained by combining the ring structure of pBNP32 with the amino- and carboxyl-terminal portions of rANF(99-126), is the most selective analog. pBNP1 displays higher affinity and agonistic potency for ANF-R1A receptor than for ANF-R1B receptor, with selectivity ratios between these two subtypes of 632- and 504-fold, respectively. Moreover, an excellent correlation is observed between the affinity of the peptides for the ANF-R1A receptor and their stimulation of particulate guanylate cyclase activity in bovine adrenal cortex (r = 0.99, p < 0.01) and rat papillary (r = 0.97, p < 0.01) membrane preparations. In addition, all the chimeric analogs in this study show affinities similar to those of rANF(99-126) and pBNP32 for the ANF-R2 receptor in NIH-3T3 membrane preparations. Importantly, the chimeric analogs pBNP1 and pBNP3, which contain the core of pBNP32 and the amino-terminal segment of rANF(99-126), display higher affinities for the ANF-R1A receptor type than for the ANF-R2 receptor type. These results indicate that the analogs combining the ring structure of pBNP32 with the amino- and/or carboxyl-terminal segments of rANF(99-126) are more selective for the ANF-R1A receptor subtype than are the natural peptides rANF(99-126) and pBNP32. PMID- 8502233 TI - Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. AB - The metabolism of imipramine by human liver microsomes was examined using a combination of five strategies. Human hepatic microsomes produced N desmethylimipramine (84%), 2-hydroxyimipramine (10%), and 10-hydroxyimipramine (6%). Preincubation of human hepatocytes in culture with beta-naphthoflavone and macrolides exclusively induced the formation of desmethylimpramine (552%, p < 0.05, and 234%, p < 0.003, respectively). Correlations were obtained between rates of imipramine demethylation and cytochrome P-450 (P-450) 1A2 (r = 0.88, p < 0.001) and P-450 3A (r = 0.80, p < 0.02) concentrations in human liver microsomal preparations from 13 different subjects. Anti-P-450 1A2 and anti-P-450 3A antibodies selectively inhibited N-demethylation (80% and 60%, respectively). N Demethylation was completely inhibited when anti-1A2 and anti-3A were added simultaneously. Kinetic studies with human microsomes confirm the contribution of two different enzymes in the N-demethylation. The Km of 1A2 was similar to the high affinity Km in human liver microsomes, whereas the Km of 3A was similar to the low affinity Km in human liver microsomes. P-450 1A2 was apparently more efficient than 3A4 (lower Km and higher Vmax) but was expressed in much lower concentration. Human P-450s 1A2 and 3A4 expressed in yeast efficiently produced desmethylimipramine. These results suggest that P-450 1A2 and P-450 3A4 are the major enzymes involved in imipramine N-demethylation in human hepatic microsomes. Similar experiments were conducted using P-450 2D6, and they confirmed that P-450 2D6 catalyzes imipramine 2-hydroxylation. Interindividual variations in 3A4 hepatic content may explain the large variations in imipramine blood levels observed after uniform dosages and thus may explain the variations in clinical efficacy. Caution might be advised in the clinical use of tricyclic antidepressants when drugs are also administered that induce or inhibit P-450s 3A4 and 1A2. PMID- 8502234 TI - Transcriptional and posttranscriptional regulation of inhibin alpha-subunit gene expression in rat Sertoli cells by 8-bromo-3',5'-cyclic-adenosine monophosphate. AB - FSH is a major regulator of inhibin production in the testis. FSH effects on Sertoli cell inhibin production are believed to be mediated, at least in part, via the cAMP second messenger system. Previously, it has been shown that 8-bromo cAMP (8-Br-cAMP) stimulates inhibin-alpha mRNA levels. This study examines whether the cAMP-induced increase in inhibin-alpha mRNA levels results from increased alpha mRNA synthesis, decreased degradation of mRNA, or both. The effects of cAMP on inhibin-alpha gene transcription were examined using nuclear run-on assays. Furthermore, the ability of 8-Br-cAMP to drive the transcription of chimeric constructs containing a 2.2-kilobase (kb) segment of the 5' regulatory region of the alpha gene placed upstream of the coding region of the luciferase reporter gene was also examined. Data from nuclear run-on assays demonstrated rapid induction of alpha gene transcription by cAMP within 2 h and maximal 4- to 5-fold increase within 4-8 h in primary Sertoli cells. Transfection of TM.4 and JEG.3 cells with an alpha (2.2 kb):luciferase chimeric construct (containing 2.2 kb of the alpha gene 5'-flanking DNA) revealed rapid time dependent induction of luciferase activity by 8-Br-cAMP in these cell types. To examine the effects of 8-Br-cAMP on alpha mRNA stability, cells were pretreated with medium or 50 micrograms/ml 8-Br-cAMP for 24 h before addition of 5 microM actinomycin D to arrest new RNA synthesis, and the decay of alpha mRNA transcripts was assessed over 24 h by Northern analysis and nonlinear regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502235 TI - Mutagenesis of essential functional residues of rat androgen-binding protein/sex hormone-binding globulin. AB - Testicular androgen-binding protein (ABP) and liver (plasma) sex hormone-binding globulin (SHBG) are extracellular carrier proteins that bind androgens with high affinity. Both proteins are encoded by the same gene and have the same primary amino acid sequence. Previous affinity labeling experiments to identify the steroid-binding site of ABP/SHBG led to ambiguous results, implicating various residues from 134 to near the C-terminus. To aid in elucidation of the essential functional residues of ABP/SHBG, we created mutant rat proteins by deletion and site-directed mutagenesis. The mutants were expressed in COS 7 green monkey kidney cells and analyzed for immunoreactive cellular and medium ABP and dihydrotestosterone (DHT) binding properties. Analysis of truncated ABP proteins revealed that removal of 26 or more residues from the C-terminus eliminates secretion and DHT-binding activity. Alteration of amino acid residues by site directed mutagenesis from residue 54 to residue 333 resulted in elimination of DHT binding for 9 of 10 mutants and reduced DHT affinity for one altered protein (ABPGly54-57). Only one of the 10 mutant ABP proteins was secreted by the COS cells. This secreted mutant ABP (ABPArg139) exhibited no detectable DHT-binding activity. Thus, our data demonstrate that modifications of the ABP primary sequence throughout the molecule have a detrimental effect on steroid binding and secretion. These data, taken together with previous affinity labeling experiments, mutagenesis studies, and the conserved residues between rat and human ABP/SHBG, indicate that at least part of active site is located in residues 139-150, but most of the protein is required to maintain the conformation of the active site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502236 TI - Insulin inhibits the estrogen-dependent expression of the chicken very low density apolipoprotein II gene in Leghorn male hepatoma cells. AB - Expression of the very low density apolipoprotein II (apoVLDLII) gene in the chicken is absolutely dependent on estrogen. ApoVLDLII mRNA is expressed in the Leghorn male hepatoma (LMH) cell line in response to estrogen in completely defined medium. Addition of serum to these cultures results in a decrease in apoVLDLII mRNA. Data in this report demonstrate that 1 nM insulin has the same inhibitory effect as 10% serum. Insulin inhibits apoVLDLII mRNA in a dose dependent manner; 100 fM insulin inhibits the estrogen-dependent response by 76%. After transfection of LMH cells with apoVLDLII sequences from an 8.9-kilobase (kb) genomic clone (pApo107) that contains the entire 2.9-kb coding sequence along with approximately 3 kb each of 5'- and 3'-flanking DNA, the estrogen dependent expression of apoVLDLII mRNA from both the endogenous gene and transfected DNA is reduced by insulin. Furthermore, insulin reduces by more than 90% the estrogen-dependent expression from a chimeric construct, pApoCAT, which contains apoVLDLII sequences -900/+1455 cloned 5' of the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. To determine the specificity of the response, expression of the pApoCAT construct was tested with insulin-like growth factor-I and insulin. Three hundred picomolar insulin inhibits the estrogen-mediated CAT activity by 50%. Insulin-like growth factor-I at this concentration has no effect or slightly increases the estrogen-dependent expression of pApoCAT, suggesting that the observed inhibitory action is mediated by the insulin receptor. Consequently, the LMH cells provide an excellent model system in which to study the molecular mechanism of insulin and estrogen interaction in the regulation of gene expression. PMID- 8502237 TI - Inhibition of mouse GATA-1 function by the glucocorticoid receptor: possible mechanism of steroid inhibition of erythroleukemia cell differentiation. AB - Treatment of mouse erythroleukemia (MEL) cells with hexamethylene bisacetamide induces a program of erythrodifferentiation, as judged by an increase in the synthesis of globins and other erythroid-specific products. This induction can be inhibited by glucocorticoids, e.g. dexamethasone. All globin and other erythroid specific genes tested contain GATA response elements (GATA-RE) and can be transactivated by GATA-1, a transcription factor. GATA-1 is highly expressed in erythroid cells, including MEL cells. We noted a glucocorticoid receptor (GR) response element motif near a GATA-RE motif in the promoter region of the mouse beta-major and beta-minor globin genes and about 130 bases away from a GATA-RE in the alpha 1-globin gene promoter and, therefore, investigated the possibility that the dexamethasone-induced inhibition of induced MEL cell differentiation may involve effects of the GR on GATA-1 activity. Evidence obtained from transfection assays and DNA electrophoretic mobility shift assays indicates that the GR binds GATA-1 and interferes with its function before any interaction with DNA, but that the presence of a glucocorticoid response element near a GATA-RE augments the GR effect. The N-terminal 106-amino acid domain of the GR was found to be essential for the effect, possibly by binding to GATA-1. Since GATA-1 is autoregulatory, i.e. it has been shown by others to bind to its own promoter and up-regulate its own transcription, the finding that activated GR can interfere with GATA-1 function may provide an explanation for the inhibition by glucocorticoids of the entire program of erythroid differentiation in MEL cells. That is, by interfering with GATA-1 function, the GR inhibits not only the expression of erythroid structural genes, but may also inhibit the expression of a primary erythroid regulatory gene, GATA-1. It was also shown that the GATA-RE in each of the beta globin promoters responds to mouse GATA-1 in a functional transfection assay. PMID- 8502238 TI - Transcriptional regulation of inhibin beta B messenger ribonucleic acid levels in TM.4 or primary rat Sertoli cells by 8-bromo-cyclic adenosine monophosphate. AB - FSH, a major regulator of inhibin production in the testis, is believed to exert its effects via cAMP second messenger system. Inhibin alpha-subunit gene appears to be regulated by cAMP and has a palindromic cAMP response element sequence TGACGTCA. However, the regulation of the inhibin beta B-subunit gene by cAMP has been less clear. It has been assumed that beta B may not be regulated by cAMP, based mainly on observations that FSH stimulates only alpha, not beta B, mRNA levels, and that the 5'-up-stream regulatory region of the beta B gene does not contain the classical cAMP response element. However, we have observed that 8 bromo-cAMP stimulates beta B mRNA levels in both primary Sertoli (approximately 2 fold) and TM.4 cells (approximately 5-fold). We examined whether this cAMP induced increase in beta B mRNA levels is the result of increased transcription or altered mRNA stability. Data from nuclear run-on assays demonstrate about a 2 fold increase in relative mRNA synthesis rates in primary Sertoli-cells and about a 4- to 5-fold increase in TM.4 cells. Transfection studies in TM.4 and JEG.3 cell lines with beta B:luciferase chimeric reporter gene constructs containing 1.5 kilobases of the beta B 5'-up-stream regulatory region revealed marked cAMP induction of reporter gene activity in both cell types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502239 TI - Developmental regulation of proopiomelanocortin gene expression in the fetal and neonatal rat pituitary. AB - Expression of the POMC gene and secretion of its peptide products are under complex regulation in the pituitary by multiple factors. CRF stimulates POMC transcription and secretion in both adult anterior (AL) and intermediate (IL) pituitary lobes, whereas glucocorticoids have an inhibitory effect on POMC in the AL, but little, if any, effect in the IL. To determine when transcriptional responses elicited by these factors begin during development and whether they undergo changes during ontogeny, we used a solution hybridization/nuclease protection assay with a POMC exon 1-intron A splice junction probe to analyze simultaneously the levels of intron A-containing POMC heterogeneous nuclear RNA (hnRNA) and POMC mRNA in explant fetal and neonatal rat pituitaries. We examined responses to 8-bromo-cAMP, CRF, and dexamethasone (dex) at stages before and after innervation of the IL by dopaminergic neurons from the hypothalamus. Treatment of embryonic day 15 (e15) whole pituitaries with CRF (10(-7) M) for 1 h led to a 2.5-fold increase in the level of POMC hnRNA, while pretreatment with dex (10(-6) M) inhibited the CRF-induced stimulation of POMC transcription. These results demonstrate that by e15, POMC transcription is already responsive to both CRF and dex, and thus, functional receptors (coupled effectively to the POMC promoter) are present by this age. Initial studies of POMC mRNA levels at early postnatal ages showed that 1 mM 8-bromo-cAMP stimulated postnatal day 1 (p1) and p10 AL and neurointermediate lobe (NIL) POMC mRNA levels, and 10(-6) M dex inhibited this stimulation in p1 AL, p10 AL, and p1 NIL, but not in p10 NIL. These studies were extended to examine POMC hnRNA responses at these ages. Treatment with CRF for 1 h increased POMC hnRNA 1.9- and 1.5-fold in p1 and p10 AL, respectively, and pretreatment with dex blocked these CRF-mediated effects on AL POMC transcription. In the NIL on p1, CRF induced a 2-fold increase in POMC hnRNA, which (like that in the AL) was inhibited by 30-min pretreatment with dex; in contrast, on p10, dex did not affect the CRF-induced increase in POMC hnRNA. The glucocorticoid receptor subtype responsible for this effect was identified using treatments with specific agonist and antagonists. The type II receptor agonist RU 28362 had an effect similar to that of dex; at both 10(-6) and 10(-8) M, RU 28362 inhibited CRF-induced increases in POMC hnRNA in p1 NIL and p1 and p10 AL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8502240 TI - C-reactive protein (CRP) binding to the Sm-D protein of snRNPS. Identification of a short polypeptide binding region. AB - C-reactive protein (CRP) binds to chromatin, histones, and small nuclear ribonucleoproteins (snRNPs) through a phosphocholine (PC)-inhibitable, calcium dependent binding site. snRNPs process pre-mRNA to mature mRNA and are composed of small uridine-rich RNAs (designated U1, U2, U5 and U4/U6) and associated proteins. We have shown that CRP binds to snRNPs in intact cells and to the U1 snRNP-specific 70 K protein in cell extracts. To determine whether CRP bound to other snRNP proteins, snRNPs were purified from rabbit thymus extract and CRP binding was assessed by blotting. CRP bound to a protein with the same mobility as Sm-D as well as to the 70 K protein. CRP specifically bound to and precipitated a fusion protein containing full-length Sm-D, confirming the binding of CRP to Sm-D. Binding was inhibited by PC and by EDTA. Binding studies using deletion mutants of the Sm-D fusion protein revealed that CRP binding was mediated by the C-terminal region of Sm-D, a region which binds autoantibodies and is proposed to bind to RNA. A comparison of the peptide regions on different autoantigens suggests that there is a shared motif to which CRP binds. PMID- 8502241 TI - Slow egress of a mouse MHC class I molecule to the cell surface despite its strong association with beta 2-microglobulin. AB - Two H-2D region class I genes from the wild-derived mouse strain B10.GAA37 provisionally encoding the Dw16 and Lw16 molecules, respectively, were transfected into mouse L cells, and the expressed gene products were analyzed serologically by flow cytometry. As expected from nucleotide sequence comparisons, these analyses revealed that several Ld-reactive monoclonal antibodies (mAbs) recognize Lw16 and not Dw16. As detected by flow cytometry of intact L.Lw16 cells and B10.GAA37 splenocytes, and by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) of immunoprecipitates from splenocyte lysates, the alpha 2 domain-reactive mAb 30-5-7 detected less Lw16 than did the alpha 3 domain-reactive mAb 28-14-8, suggesting the existence of two populations of Lw16 molecules: 30-5-7+ 28-14-8+ and 30-5-7- 28-14-8+. Sequential immunoprecipitation studies provided further evidence for these two Lw16 subsets; furthermore, the 30-5-7- 28-14-8+ subset was found predominantly on the cell surface and in association with beta 2-microglobulin (beta 2-m). Pulse-chase studies of B10.GAA37 splenocytes revealed that Lw16, like Ld, is trafficked slowly to the cell surface, whereas Dw16 is trafficked quickly, like most other mouse K and D region class I molecules. Despite these similarities, Lw16 and Ld differ in their association with beta 2-m, in that the immunoprecipitates of Lw16 contained much higher levels of radiolabeled beta 2-m per heavy chain. Together, these studies indicate that the slower trafficking of Lw16 to the surface does not result from a weaker association with beta 2-m, suggesting that other factors, such as peptide ligand-induced assembly, and/or retention by ER-resident proteins play an important role in the trafficking of major histocompatibility (MHC) class I molecules to the cell surface. PMID- 8502242 TI - Control of IgG/Fc glycosylation: a comparison of oligosaccharides from chimeric human/mouse and mouse subclass immunoglobulin Gs. AB - Oligosaccharide profiles were obtained for chimeric mouse-human antibodies corresponding to each of the human IgG subclasses 1-4, and mouse IgG2b antibodies each expressed in the mouse J558L cell line. These antibodies have specificity for the NIP hapten and form a matched set of IgGs. An IgG4 chimeric antibody (B72.3) produced in the chinese hamster ovary (CHO-K1) cell line was also analysed for carbohydrate. Additionally aglycosylated mutants of this IgG4 (B72.3) and anti-NIP mouse IgG2b were analysed. The total lack of carbohydrate found in the aglycosylated site-directed mutants human chimeric IgG4 B72.3 (Asn 297-->Gln) and mouse IgG2b (Asn 297-->Ala) demonstrates that there are no N glycosylation sites other than Asn 297. Therefore glycosylation profiles for all the IgGs analysed reflect carbohydrate attached to this site. Factors such as cell type (A), template direction by the IgG heavy chains (B) and culture conditions (C) are shown to influence IgG glycosylation profiles. (A) The anti NIP IgG antibodies expressed by the J558L cell line may have one or two Gal (alpha 1-->3) Gal residues per oligosaccharide unit, indicative of the presence of (alpha 1-->3) galactosyl transferase in the J558L mouse cell line. (B) The galactosylation profiles obtained for the IgG heavy chains, in particular the preference for galactosylation of the Man (alpha 1-->6) arm rather than the Man (alpha 1-->3) arm, contrary to the beta-galactosyltransferase specificity, suggest that the polypeptide chain may act as a template to influence the extent of galactosylation and hence the proportions of each oligosaccharide incorporated. The IgG2 antibody does not display this galactosylation preference. (C) The extent of galactosylation appears to be influenced by the growth conditions, with the highest levels of galactosylation being found for IgG produced by cells grown in still cultures, rather than cells grown as ascites or in hollow fibre bioreactors. It is concluded that though the profile of glycosylation is controlled predominantly by the glycosylation activity of the cell in which the IgG is expressed, differences between the IgG heavy chain templates of the various subclasses and culture conditions can also influence glycosylation. PMID- 8502243 TI - Induction of a proteoglycan core protein mRNA in mouse T lymphocytes. AB - The mouse T lymphocyte cell line EL4.E1 synthesizes a proteoglycan core protein (PGCP) mRNA which is identical to serglycin mRNA found in mouse bone marrow derived mast cells and a mouse mastocytoma cell line. PGCP mRNA was strongly induced in EL4.E1 cells by phorbol myristate acetate, which also induces mRNAs for several cytokines in these cells. In contrast to the induction of cytokine mRNAs, however, the induction of PGCP mRNA was not inhibited by Cyclosporine. PGCP mRNA was also inducible by allogeneic stimulation of normal mouse spleen cells, and by Con A stimulation of an Interleukin 2-producing T hybridoma cell line. A number of other cell lines expressed an identical or similar, mRNA, including two cytotoxic T cell lines, and three tumor cell lines related to bone marrow-derived cells. The levels of several proteoglycans have previously been reported to increase in cells of bone marrow origin under activating conditions, but this appears to be the first report of an induction of the corresponding PGCP mRNA by immune stimulation of T lymphocytes. PMID- 8502244 TI - CD32C (Fc gamma RIIC) mRNA expression and regulation. AB - The cell surface expression of the CD32 receptors for the Fc portion of immunoglobulin G (Fc gamma RII-CD32) is regulated by agents such as phorbol esters (PMA) and cytokines. In this study, we investigated the effects of PMA and interferon-gamma (IFN-gamma) on the expression of CD32C mRNA in U937 cells. When U937 (CD32+) cells are incubated with either PMA or IFN-gamma a significant enhancement of CD32C mRNA expression is observed with maximum enhancement at 18 hrs post-PMA and IFN-gamma addition. The addition of actinomycin D (ActD), a transcriptional inhibitor, together with either PMA or IFN-gamma diminishes the enhanced levels of CD32C mRNA to the basal levels, indicating that transcriptional regulation is involved in this modulatory process. The addition of cyclohexamide (CX), a protein synthesis inhibitor, to cultures undergoing stimulation with either PMA or IFN-gamma, increased the levels of CD32C mRNA synthesis suggesting that regulatory degradation proteins may be involved. The PMA and IFN-gamma stimulated CD32C mRNA is degraded within 2 hr post-stimulation and this degradation is delayed by the inhibition of de novo protein synthesis. These results, taken together with our previous studies of CD32A mRNA regulation in U937 cells stimulated with PMA, indicate that both the CD32A and C isomer mRNAs are rapidly degraded; however, CD32A and C isomer mRNAs are differentially regulated. At the optimal PMA dose, the time of mRNA stimulation of CD32A and C mRNA varies and the addition of CX to U937 cells together with PMA enhanced the levels of CD32C mRNA but had no effect on CD32A mRNA levels. These results imply that the differential regulation of the two CD32 isomers may result in differential function. PMID- 8502245 TI - Nucleotide sequence of the membrane form of sheep IgM and identification of two C mu allotypes. PMID- 8502246 TI - Pathobiology of parathyroid hormone and parathyroid hormone-related protein: introduction and evolving concepts. PMID- 8502247 TI - Mechanisms of human autoimmune thyroid disease--1992. PMID- 8502248 TI - Current concepts in follicular tumors of the thyroid. PMID- 8502249 TI - Papillary carcinoma. PMID- 8502250 TI - Fine needle aspiration of the thyroid. PMID- 8502251 TI - Pathology of hyperparathyroidism: a practical approach. PMID- 8502252 TI - Pathobiology of the C-cells. AB - This brief review of the pathobiology of C-cells has stressed cellular and molecular aspects of MTC development. In the genetic forms of MTC, an alteration in one or more genes on chromosome 10, through an as yet unknown series of events, results in initial hyperproliferation of C-cells. Subsequent genetic steps, possibly at other chromosome loci, presumably result in selected clonal transformation of the hyperproliferative C-cells at risk for tumor development. Some of these same molecular events are probably operative in the development of sporadic MTC as well. Once MTC has developed, it has the potential to undergo tumor progression events which result in loss of C-cell differentiation. Studies in a culture model of these events have revealed that activation of signal transduction pathways, similar to those active in differentiation of other neural crest-derived cells, can restore differentiation features of normal C-cells to MTC. Continued identification of the molecular factors mediating this restoration should teach us much about the relationships between general neural crest differentiation and that of normal C-cells. It will also reveal much about the pathobiology of C-cells contributing to each step of MTC development. PMID- 8502253 TI - The pathology of medullary thyroid carcinoma and its precursors. PMID- 8502254 TI - Potassium channels from normal and denervated mouse skeletal muscle fibers. AB - The properties of singles K+ channels in normal and denervated muscles were compared using the "patch-clamp" technique. Single channels were recorded from vesicles obtained by stretching bundles of normal and denervated extensor digitorium longus (EDL) muscles. The most frequently observed channel in normal muscles was a high conductance (266 pS) Ca++ activated K+ channel. Although channel density, as estimated by patch recording, showed a significant decrease in denervated muscles, no differences were found in conductance and gating properties. Another voltage-dependent K+ channel (81 pS) was only recorded from normal muscles, but never from denervated ones. In addition, a 35 pS conductance was recorded from both normal and denervated fibers. This channel displayed neither voltage dependence nor sensitivity to tetraethylammonium (TEA). In contrast, another TEA-insensitive (16 pS) channel was recorded only from denervated muscles. We conclude that denervation induces significant changes in the distribution and expression of K+ channels in mammalian skeletal muscles. PMID- 8502255 TI - Acute conduction block in vitro following exposure to antiganglioside sera. AB - We studied the role of antiganglioside antibodies in the pathogenesis of autoimmune neuropathies using an in vitro preparation of a rat sciatic nerve. Human and rabbit sera with high titers of the antibodies were applied to a restricted segment of the sciatic nerve mounted in a recording chamber, and the compound nerve action potentials of the myelinated and unmyelinated fibers were observed. Myelinated fiber conduction became blocked at the segment within a few hours, whereas the unmyelinated fiber conduction remained unchanged. These results suggest that antiganglioside sera directly produce an acute conduction block only in myelinated nerve fibers and that this in vitro model is useful for studying the ionic mechanism by which the acute conduction block occurs. PMID- 8502256 TI - Muscle glucose-6-phosphate dehydrogenase deficiency: restoration of enzymatic activity in hybrid myotubes. AB - A high level of glucose-6-phosphate dehydrogenase (G6PD) activity was observed in myoblasts and myotubes from normal human and mouse cell cultures. However, only a residual amount of activity was observed in myoblasts and myotubes obtained from G6PD-deficient patients (G6PD Mediterranean). Hybrids were formed by the fusion of normal (from human and mouse) and G6PD-deficient myoblasts (from the patients). These hybrids contained a high level of G6PD activity. Hoechst staining permitted to confirm that the enzymatic activity was not restrained to a domain near the competent nuclei. These results suggest that myoblast transplantation could be used to restore normal enzymatic activity in metabolic myopathies. PMID- 8502257 TI - EMG power spectrum of respiratory and skeletal muscles during static contraction in healthy man. AB - Changes in EMG power spectrum during isometric voluntary contraction maintained until exhaustion in the range of 20-80% MVC were studied in three skeletal muscles (adductor pollicis or AP, vastus lateralis, and medialis) and two respiratory muscles (diaphragm and rectus abdominis). Quantitative EMG analysis consisted of computation of the median frequency (MF) of power spectra and also the continuous measurement of EMG power in two bands of high (EH) and low (EL) frequencies using bandpass filters. This allowed the calculation of the H/L ratio and its time constant of decay rate (TC delta H/L) throughout the sustained static contraction. The main results were: (1) highly significant, positive correlations between TC delta H/L and the maximal MF changes and also the endurance time to fatigue; (2) EMG changes were determined early, within the first 10-20 s of contraction; and (3) EL always increased throughout the fatiguing isometric contraction, but EH changes markedly varied within the five muscle groups studied. These observations are discussed in terms of the differences in muscle fiber composition and also the variations in motor unit recruitment. PMID- 8502258 TI - Conduction abnormalities induced by sera of patients with multifocal motor neuropathy and anti-GM1 antibodies. AB - Increased titers of anti-GM1 antibodies have been associated with motor neuron disease and motor neuropathy with or without conduction block. To investigate the pathogenetic role of anti-GM1 antibodies we injected into rat tibial nerves sera from patients with multifocal motor neuropathy and conduction block (MMN) or progressive spinal muscular atrophy (PMA), both presenting anti-GM1 antibodies. Sera of patients with MMN produced reduction of amplitude and dispersion of compound muscle action potential from proximal stimulation. Morphometry revealed demyelination in 6.2% of fibers. Sera of patients with PMA did not produce clear cut electrophysiological or morphological changes. Differential effects of sera from patients presenting high-titer anti-GM1 antibodies, but with distinct clinical syndromes, might depend on differences in anti-GM1 antibody affinity, valency, or ability to fix complement. Alternatively, circulating factors other than, or in addition to, anti-GM1 antibodies present in sera of patients with MMN, but not of PMA patients, might be responsible for conduction abnormalities and reproduce them after passive transfer. PMID- 8502259 TI - Multifrequency characteristics of disposable and nondisposable EMG needle electrodes. AB - The physical properties of recording electrodes coupled with the input characteristics of recording amplifiers can affect motor unit parameters. In recent years, there has been increased use of disposable needle electrodes; thus, a comparison of impedance characteristics with disposable types is of interest. Impedances at 10, 100, 1000, and 10,000 Hz of eight different electrode models including concentric and monopolar, both disposable and reusable, were measured. For all models of monopolar electrodes, no significant difference in impedance was found between disposable and nondisposable types. Intramodel variability was seen, however, with a twofold difference between minimum and maximum impedances for each model. For concentric electrodes, a moderate difference in impedance was found between disposable and nondisposable types, but less intramodel variability was seen; there was also more intermodel variability. To determine whether the measured impedances could affect recorded motor unit potentials, a theoretical analysis was conducted using typical waveforms along with circuit analysis techniques. Electrode impedances as high as 50 times nominal values caused no significant waveform distortion. PMID- 8502260 TI - Recombinant growth hormone treatment of amyotrophic lateral sclerosis. AB - Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced. PMID- 8502261 TI - A comparison of electric and magnetic compound action signals as quantitative assays of peripheral nerve regeneration. AB - The evaluation of peripheral nerve regeneration is of great interest in clinical as well as in experimental situations. However, there are few techniques that give early and quantitative information on the status of the regeneration process. If quantitative assays would be available, different surgical techniques and medications could be evaluated more accurately in relation to axonal ingrowth and functional recovery. The purpose of this study was to investigate the merits of nerve compound action signals (NCASs) recorded electrically and signals recorded with a novel magnetic recording technique. We compared the two techniques in the rabbit peroneal nerve, 2, 4, 6, and 8 weeks after a nerve reconstruction. Our conclusions are that the signals recorded with the magnetic sensor are far more reproducible and less prone to stimulus artifact than the electrically recorded signals. Furthermore, the magnetic recording shows that the number of axons that have regenerated increases with time. Previously, this could only be determined with histological studies. Other ingrowth parameters that can be quantified are the average ingrowth distance, and the variation between axons in ingrowth velocity. PMID- 8502262 TI - Association of IgG anti-GD1a antibody with severe Guillain-Barre syndrome. AB - We earlier reported cases of 2 patients with severe acute Guillain-Barre syndrome (GBS) associated with high-IgG anti-GD1a antibody titer. We now have investigated the autoantibody against GD1a or GM1 in 37 GBS patients using the enzyme-linked immunosorbent assay and have found a statistically significant association between IgG anti-GD1a antibody and the severity of the disease (need of a respirator for more than 1 month and a poor functional prognosis 3 months after neurologic onset). An autopsy which showed severe GBS associated with IgG anti GD1a antibody produced the following findings: (1) severe axonal degeneration and segmental demyelination of peripheral nerves; (2) lymphocytic infiltration; and (3) marked central chromatolysis of the lower motoneurons. PMID- 8502263 TI - Comparison of directly stimulated with axon-reflex-mediated sudomotor responses in human subjects and in patients with diabetes. AB - The muscarinic receptors of human eccrine sweat gland may be directly stimulated by iontophoresis of acetylcholine (direct response; DIR) and indirectly via nicotinic receptors and an axon "reflex" (AXR). Using a specially designed multicompartmental sweat cell and dual sudorometers, we were able to simultaneously record the evoked DIR and AXR responses. On a second day, we repeated the experiment under identical ambient and stimulus conditions but instead obtained silastic imprints of DIR and AXR for morphometry. Studies were done on 24 controls (mean +/- SD = 47.6 +/- 15.1 years) and 23 diabetic subjects (mean +/- SD = 49.6 +/- 16.3 years). In control subjects, sudorometric DIR recordings were consistently larger than AXR. There was no difference in sweat droplet density by sex, but the size of droplets was larger in males. In diabetic patients 3 of 23 had absent AXR but preserved DIR, suggesting that failure of AXR preceded DIR in patients with neuropathy. Patients with mild neuropathy had an overrepresentation of large diameter droplets in the silastic imprints of both DIR and AXR, while patients with severe neuropathy had a markedly reduced density and small diameter droplets. PMID- 8502264 TI - Discharge properties of single motor units in patients with spinal cord injuries. AB - To study neurophysiological correlates of spastic paresis, we analyzed the discharge pattern of single motor units (SMUs) during sustained voluntary contraction from muscles weakened by spinal cord injury (SCI) and from muscles of near normal strength just at or above the level of injury. The average firing rate of SMUs was reduced in patients' biceps brachii and tibialis anterior muscles compared with controls, but not in the triceps brachii. Floating serial correlation coefficients obtained from successive interdischarge intervals were significantly more positive in patients than in controls in all three muscles. One statistical measure of regularity of discharge, akin to a coefficient of variation, was best able to differentiate patient and control SMUs. Increased discharge variability in muscles just above the level of injury suggested that subtle effects of traumatic SCIs were more extended than was clinically apparent. Although consistent statistical differences could be measured, these changes were not specific to SCI, nor were all SMUs equally affected. PMID- 8502265 TI - Adult acid maltase deficiency. AB - A 30-year-old man was referred for neurologic evaluation because of elevated creatine kinase. He had noted symptoms of proximal arm and distal leg weakness for several years, and, on examination, he had weakness in a scapuloperoneal distribution. An electromyogram showed myotonic discharges in the paraspinous muscles, and a muscle biopsy revealed severe vacuolar myopathy. Biochemical analysis of muscle showed acid maltase deficiency. The patient's only brother had childhood-onset acid maltase deficiency and died of respiratory failure at age 27. Acid maltase deficiency may have heterogeneous presentations within a family, and adult AMD can present as a scapuloperoneal neuromuscular syndrome. PMID- 8502266 TI - Progressive sensory radiculopathy responsive to corticosteroid therapy. PMID- 8502267 TI - Isolated dysphagia due to polymyositis. PMID- 8502268 TI - SEPs and CNS magnetic stimulation in syringomyelia. PMID- 8502269 TI - A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. AB - BACKGROUND: Group B streptococci (Streptococcus agalactiae) are a major cause of meningitis and septicemia in neonates and pregnant women, but the importance of group B streptococcal disease in nonpregnant adults has not been clearly defined. METHODS: We conducted a prospective surveillance of the pathogens responsible for meningitis for a period of 24 months in 35 hospitals and a referral laboratory in metropolitan Atlanta. We reviewed the clinical and laboratory records of all the nonpregnant adults identified as having invasive group B streptococcal disease during this period. RESULTS: During 1989 and 1990 there were 424 patients with invasive group B streptococcal disease (annual incidence, 9.2 cases per 100,000 population). Of these patients, 46 percent were 1 month of age or younger, 6 percent were older than 1 month but younger than 18 years of age, and 48 percent were 18 or older. Men and nonpregnant women accounted for 68 percent (n = 140) of all cases among adults (annual incidence, 4.4 per 100,000). Clinical and laboratory records were available for 137. In the nonpregnant adult patients (age, 18 to 99 years), the most common clinical diagnoses were skin, soft-tissue, or bone infection (in 36 percent); bacteremia with no identified source (30 percent); urosepsis (14 percent); pneumonia (9 percent); and peritonitis (7 percent). Risk factors included older age (> or = 60 years), the presence of diabetes mellitus, the presence of malignant neoplasms, and infection with the human immunodeficiency virus. The mortality rate in nonpregnant adults was 21 percent, accounting for 67 percent of all deaths related to group B streptococcal infection during the surveillance period. CONCLUSIONS: Invasive group B streptococcal infection is a major problem not only in pregnant women and neonates but also in nonpregnant adults, especially those who are elderly and those who have chronic diseases. PMID- 8502270 TI - Effect of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. AB - BACKGROUND: In several studies dietary fish oil has been found to have beneficial effect on psoriasis, but the results are contradictory and based mainly on open studies or studies of small numbers of patients. METHODS: In a four-month double blind, multicenter trial, we randomly assigned 145 patients with moderate-to severe psoriasis to receive in their diet either highly purified ethyl esters of n-3 fatty acids ("fish oil"; 6 g of oil per day, containing 5 g of eicosapentaenoic and docosahexaenoic acid) or an isoenergetic amount of corn oil containing mainly n-6 fatty acids. All the patients were advised to reduce their intake of saturated fatty acids. A 48-hour dietary recall was performed, and the fatty-acid pattern in the serum phospholipids was monitored in a subgroup of patients. RESULTS: In the fish-oil group, n-3 fatty acids were increased in serum phospholipids (P < 0.001), the ratio of arachidonic acid to eicosapentaenoic acid decreased (P < 0.001), and the level of n-6 fatty acids decreased (P < 0.001). In the corn-oil group, only docosahexaenoic acid increased significantly (P < 0.05). The ratio of polyunsaturated to saturated fatty acids increased in both groups. Plasma concentrations of triacylglycerol decreased from base line in the fish-oil group (P < 0.05). The score on the Psoriasis Area and Severity Index, as evaluated by the physicians, did not change significantly during the trial in either group. This was also true of a total subjective score reported by the patients, but a selected area of skin in the corn-oil group showed a significant reduction in the clinical signs (P < 0.05). Scaling was reduced from base line in both groups (P < 0.01). The fish-oil group had less cellular infiltration (P < 0.01), and the corn-oil group had improvement in desquamation and redness (P < 0.05). There was no significant difference in clinical manifestations between the groups. Among the patients in the fish-oil group, an increase in the concentration of n-3 fatty acids in serum phospholipids was not accompanied by clinical improvement, whereas in the corn-oil group there was a significant correlation between clinical improvement and an increase in eicosapentaenoic acid and total n-3 fatty acids. CONCLUSIONS: Dietary supplementation with very-long chain n-3 fatty acids was no better than corn-oil supplementation in treating psoriasis. Clinical improvement was not correlated with an increase in the concentration of n-3 fatty acids in serum phospholipids among the patients in the fish-oil group, whereas there was a significant correlation between clinical improvement and an increase in eicosapentaenoic acid and total n-3 fatty acids in the corn-oil group. PMID- 8502271 TI - Brief report: myeloma-associated paraprotein directed against the HIV-1 p24 antigen in an HIV-1-seropositive patient. PMID- 8502272 TI - Prevention and treatment of traveler's diarrhea. PMID- 8502273 TI - Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. PMID- 8502274 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 25-1993. A 67-year-old man with osteolytic lesions of T11 and T12. PMID- 8502275 TI - The changing spectrum of group B streptococcal disease. PMID- 8502276 TI - Psoriasis therapy--observational or rational? PMID- 8502277 TI - Sympathetic-nerve activity during sleep. PMID- 8502278 TI - The health benefits of exercise. PMID- 8502279 TI - Central venous pressure in space. PMID- 8502280 TI - Pathogenesis and treatment of gallstones. PMID- 8502281 TI - Pathogenesis and treatment of gallstones. PMID- 8502282 TI - Pathogenesis and treatment of gallstones. PMID- 8502283 TI - Pathogenesis and treatment of gallstones. PMID- 8502284 TI - Conference unwanted. PMID- 8502285 TI - Biomedical trust fund is proposed to support basic research at NIH. PMID- 8502286 TI - Life sciences take a dive. PMID- 8502287 TI - Smithkline backs sequencing company. PMID- 8502288 TI - Australian state wants claim to native plants. PMID- 8502289 TI - AIDS activists says basic research is underfunded. PMID- 8502290 TI - Rumoured good news raises share price of vaccine company. PMID- 8502291 TI - AIDS: striking the happy media. AB - The past year has seen many controversies about AIDS research and researchers. What productive events have occurred, and what is likely to happen in the next year? PMID- 8502292 TI - AIDS: trends, predictions, controversy. AB - One of the persistent controversies that surfaces in the media about AIDS is whether the heterosexual population is at risk. The latest projections provide an emphatic affirmative. PMID- 8502293 TI - Evolutionary genetics. Siberian mice upset Mendel. PMID- 8502294 TI - Drug design. A rational attack on influenza. PMID- 8502295 TI - Rational design of potent sialidase-based inhibitors of influenza virus replication. AB - Two potent inhibitors based on the crystal structure of influenza virus sialidase have been designed. These compounds are effective inhibitors not only of the enzyme, but also of the virus in cell culture and in animal models. The results provide an example of the power of rational, computer-assisted drug design, as well as indicating significant progress in the development of a new therapeutic or prophylactic treatment for influenza infection. PMID- 8502296 TI - Naturally occurring antibodies devoid of light chains. AB - Random association of VL and VH repertoires contributes considerably to antibody diversity. The diversity and the affinity are then increased by hypermutation in B cells located in germinal centres. Except in the case of 'heavy chain' disease, naturally occurring heavy-chain antibodies have not been described, although antigen binding has been demonstrated for separated heavy chains or cloned VH domains. Here we investigate the presence of considerable amounts of IgG-like material of M(r) 100K in the serum of the camel (Camelus dromedarius). These molecules are composed of heavy-chain dimers and are devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, a finding that calls into question the role of light chains in the camel. Camel heavy-chain IgGs lack CH1, which in one IgG class might be structurally replaced by an extended hinge. Heavy-chain IgGs are a feature of all camelids. These findings open new perspectives in the engineering of antibodies. PMID- 8502297 TI - MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1. AB - Tissue-specific homing of lymphocytes is regulated by interactions with the endothelium of specialized venules, such as the high endothelial venules (HEV) in lymph nodes and mucosal lymphoid tissues. The mucosal vascular addressin, a 58 66K glycoprotein adhesion receptor for lymphocytes, is selectively expressed on HEV of mucosal lymphoid organ and on lamina propria venules and helps direct lymphocyte traffic to these mucosal tissues. We now report the isolation of a complementary DNA that, on transfection into COS cells, encodes immunoreactive addressin that specifically binds the mucosal HEV-binding T-cell lymphoma TK1. The predicted amino-acid sequence defines the mucosal addressin as a novel immunoglobulin family member, MAdCAM-1, with two amino-terminal domains that display strong homology to previously described vascular adhesion receptors for leukocytes, ICAM-1 (ref. 6) and VCAM-1 (ref. 7). The membrane proximal domain is homologous to the third domain (C alpha 2) of another mucosa-associated immunoglobulin family member, IgA1 (refs 8, 9). In addition to the immunoglobulin domains, there is a serine/threonine-rich region which may serve as a backbone to present carbohydrate ligands to lymphocytes. MAdCAM-1 is thus a complex multidomain receptor displaying several structural motifs that may participate in lymphocyte homing interactions. PMID- 8502299 TI - Capturing scarce resources: documentation and communication. AB - When charting does not reflect nursing activities, reimbursement may be denied. Skilled nursing care documentation of quality care rendered allows for reimbursement. Accountability for nursing care goes beyond planning and implementation; it also includes responsible recording and communication of activities. There are many chronic conditions that benefit from nursing intervention yet are not part of admitting diagnoses. Urinary incontinence is an example of a common problem encountered by nurses in hospital settings that requires time, patience, knowledge, and skill to assist those having this condition. It is cost effective to provide the care necessary to improve the treatment and management of urinary incontinence; it is revenue effective to assure that nursing and medical documentation is complete to cover the cost of nursing time and expertise spent providing care to patients with this condition. PMID- 8502298 TI - The origin of HIV-1 isolate HTLV-IIIB. AB - The striking similarity between the first two human immunodeficiency virus type 1 (HIV-1) isolates Lai/LAV (formerly LAV, isolated at the Pasteur Institute) and Lai/IIIB (formerly HTLV-IIIB, reported to be isolated from a pooled culture at the Laboratory of Tumor Cell Biology (LTCB) of the National Cancer Institute) provoked considerable controversy in light of the high level of variability found among subsequent HIV-1 isolates. In November 1990, the Office of Scientific Integrity at the National Institutes of Health commissioned our group to analyse archival samples established at the Pasteur Institute and LTCB between 1983 and 1985. Retrospective analyses have shown that contamination of a culture derived from patient BRU by one from patient LAI was responsible for the provenance of HIV-1 Lai/LAV; the contaminated culture (M2T-/B) was sent to LTCB in September 1983. Our goals were to determine which HIV-1 variants were present in the samples and the sequence diversity among HIV-1 isolates from the earliest stages of the AIDS epidemic. We examined archival specimens and report here the detection of six novel HIV-1 sequences in the cultures used to establish the pool: none is closely related to HIV-1 Lai/IIIB. A sample derived from patient LAI contained variants of both HIV-1 Lai/IIIB and HIV-1 Lai/LAV, and a sequence identical to a variant of HIV-1 Lai/IIIB was detected in the contaminated M2T-/B culture. We conclude that the pool, and probably another LTCB culture, MoV, were contaminated between October 1983 and early 1984 by variants of HIV-1 Lai from the M2T-/B culture. Therefore, the origin of the HIV-1 Lai/IIIB isolate also was patient LAI. PMID- 8502300 TI - Hero making through storytelling: the nurse manager's challenge. AB - Storytelling is an effective way of transferring knowledge and values from one person to another. Stories can cross individual, cultural, and educational differences more powerfully than most other methods of learning. For thousands of years stories have been used for teaching. A hospital in California, Alta Bates Medical Center, has begun to use fairy tales to show the affect employees have on patients. Managing by stories offers an exciting way to approach mentoring, orientation, governance, and patient/family teaching. You can't be everywhere and you can't touch all the people in your unit. Your stories, however, will live around the clock when you are not there. Your stories will guide your unit much more successfully than management based on information alone. Try it! PMID- 8502301 TI - Seize the moment. PMID- 8502302 TI - Changes in health care highlight Clinton's economic plan. PMID- 8502303 TI - Come fly with me. PMID- 8502304 TI - An interview with Kathryn J. McDonagh. AB - Kathryn J. McDonagh, MSN, RN, CNAA, is president of Saint Joseph's Hospital of Atlanta and senior vice president of Saint Joseph's Health System. In this interview she discusses the commitment to excellence and compassionate care which is necessary for a successful health care institution, the role of a nurse as a hospital president, and advises nurse executives who are seeking CEO positions in health care. PMID- 8502305 TI - Hospital culture--why create one? AB - Hospitals, to survive, must be transformed into responsive, participative organizations capable of new practices that produce improved results in both quality of care and service at reduced costs. Creating, managing, and changing the culture are critical leadership functions that will enable the hospital to succeed. Strategic planning and effective implementation of planned change will produce the desired culture. Work restructuring, a focus on quality management along with changes in clinical practices, as well as the care and support processes, are all a part of the necessary hospital cultural revolution. PMID- 8502306 TI - Forecasting ambulatory clinic workload to facilitate budgeting. AB - Concern about controlling health care costs is a driving force in forecasting workload. The availability of computers and spreadsheet software now makes it possible for middle managers to forecast future workload using past workload data. PMID- 8502307 TI - Influencing the rising costs of health care: a staff nurse's perspective. AB - In the current atmosphere of rising health costs and increasing hospital expenditures, nurses must take an active role in seeking solutions to these problems. The staff nurse can positively influence the events that occur when a person is admitted into the hospital and can play a major role in the functioning of the organization as a whole, which in turn affects the larger domains of society. PMID- 8502308 TI - Span of control on nursing inpatient units. AB - Managerial span of control is a concept that is receiving increased attention as nurse executives attempt to maximize human resources within tight fiscal controls. Data are presented to demonstrate variations in spans of control as well as highlight underlying issues that need further clarification. PMID- 8502309 TI - Costing out nursing services: examining the research. AB - A review of 73 published and unpublished studies revealed a lack of agreement on how the terms "direct nursing care" and "total" and "direct nursing costs" are defined. A literature review and specific definitions for future research are presented. PMID- 8502310 TI - Orphan products: drugs and devices for rare diseases. AB - The issues of orphan products include an inadequate definition of orphan status that hampers implementation of the legislation, difficulties in evaluating the products themselves in order to ensure safety and effectiveness, neglect in developing orphan devices, and conflict over creating unnecessary monopolies and excessive profits. However, it has been demonstrated that the ODA is effective in stimulating the development of these much needed drugs and devices. The next efforts therefore can be directed toward increasing the effectiveness and ensuring the equity of the program. PMID- 8502311 TI - Pharmacologic intervention to prevent hemodialysis vascular access thrombosis. PMID- 8502312 TI - Effects of acetate on left ventricular function in hemodialysis patients. AB - Two approaches were chosen to assess the controversially debated influence of acetate on the heart in dialysis patients: (1) To separate acetate effects from influences of dialysis, acetate was infused in 12 chronic dialysis patients with normal systolic function on a dialysis-free day, and left ventricular (LV) function was assessed by LV pressure/volume loops. Hyperacetatemia (3-5 mmol/l) resulted in a decrease in LV preload (LV end-diastolic pressure decreased from 16 +/- 3 to 10 +/- 4 mm Hg, p < 0.01) but had no influence on LV contractility. (2) In 8 dialysis patients without cardiac disease, isovolemic acetate or bicarbonate dialysis was performed. During both procedures, there were comparable changes in serum electrolytes as well as in echocardiographic parameters. LV contractility measured by velocity of circumferential fiber shortening increased during acetate and bicarbonate dialysis (1.47 +/- 0.22 to 1.77 +/- 0.29, p < 0.01; 1.47 +/- 0.21 to 1.70 +/- 0.22 circ/s, p < 0.01). It is concluded that mild hyperacetatemia does not influence LV contractility and that dialysis-induced changes in serum electrolytes are responsible for the increase in LV contractility during dialysis. However, the pronounced acetate effect on LV preload implies considerable therapeutic implications. PMID- 8502313 TI - Lipid peroxidation abnormalities in hemodialyzed patients. AB - In order to test the existence of a possible oxidative damage during hemodialysis, plasma conjugated dienes (CD), plasma and red blood cell (RBC) thiobarbituric acid (TBA) reactants were investigated in 25 patients receiving regular dialysis treatment (RDT). The RBC TBA reactant concentration was significantly increased in RDT patients in comparison with healthy subjects. The extracellular antioxidant systems were evaluated by the assay of plasma antioxidant activity, plasma tocopherol, urate, transferrin, haptoglobin and ceruloplasmin levels. Except urate and transferrin, none of these parameters were different between the two groups. On the other hand, in RDT patients, RBC superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were significantly lower than in healthy subjects. There was an inverse correlation between decreased RBC GPX and RBC TBA reactant concentration. These results show in RDT patients the existence of an oxidizing stress, mainly intracellular, which could be due, in part, to a decrease in SOD and GPX activities. PMID- 8502314 TI - Biometrological evaluation of the stratum corneum texture in patients under maintenance hemodialysis. AB - Xerosis and hydration of the stratum corneum were evaluated in 60 hemodialyzed patients. Xerosis and a low capacitance of the stratum corneum were evidenced in more than 80% of the patients. Pruritus was present in two third of the subjects. We failed to disclose any significant relationship between severity of these three parameters. PMID- 8502315 TI - Renal toxicity mediated by continuous infusion of recombinant interleukin-2. AB - Interleukin-2 (IL-2), a potent lymphokine with antitumoral activity, was used in continuous intravenous infusion for 5 days (18,000,000 IU/m2/day) in 9 treatment cycles in 5 patients with metastatic colorectal carcinoma. During the infusion, patients received aggressive fluid replacement titrated by invasive hemodynamic monitoring, aiming at a stable central volemia. Body weight went up an average of 4.5 kg in 5 days, mean arterial blood pressure dropped slightly from day 1 to day 5 (105.4 +/- 11.6 to 86.1 +/- 12.5 mm Hg, p < 0.05), systemic vascular resistance decreased from 1304.7 +/- 242.1 to 871.7 +/- 237.2 dyn/s/cm-5 (p < 0.05), with stable pulmonary capillary wedge pressure, cardiac output and central venous pressure. The urinary output significantly dropped from 1.9 +/- 1.2 to 0.2 +/- 0.1 ml/min (p < 0.05) with very significant rises in serum creatinine from 76.0 +/- 28.3 to 242.2 +/- 144.9 mumol/l (0.86 +/- 0.32 to 2.47 +/- 1.64 mg/dl) and N acetyl-beta-D-glucosaminidase urinary activity from 4.97 +/- 5.0 to 23.0 +/- 12.1 U/l, and significant decrement of creatinine clearance (1.86 +/- 0.65 to 0.29 +/- 0.27 ml/s or 111.5 +/- 38.9 to 17.1 +/- 16.6 ml/min) and urinary sodium (113.8 +/ 78.3 to 9.0 +/- 6.7 mmol/l). Urine sediment evolved from normal at day 1 to 9.0 +/- 3.7 epithelial cells/mm3 and 6.9 +/- 3.6 brown casts/mm3 (p = 0.001). We concluded that cancer treatment with IL-2 in continuous infusion, even with stable hemodynamics, induces an acute renal failure in most patients treated. PMID- 8502316 TI - Urinary changes in ultra long-distance marathon runners. AB - The urine of 45 athletes, male and female, were studied after completing an ultra long-distance marathon race. Of these athletes, 24.4% were found on screening to have red blood cells in the urine. The urinary mean corpuscular volume (MCV) of red cells was used in an attempt to differentiate between lower and upper urinary tract haematuria. With the exception of 1 athlete, the red cells were not dysmorphic and had an MCV greater than 72 fl. This suggested that the haematuria had an origin from the lower urinary tract. The urinary changes disappeared within 7 days. No definite residual renal damage could be established. PMID- 8502317 TI - Primary glomerulonephritis with predominant mesangial immunoglobulin G deposits- a distinct entity? AB - Six cases of primary glomerulonephritis with predominant IgG deposits in the mesangium are described on the basis of a review of renal-biopsy-proven 1,116 cases with primary glomerulonephritis between 1977 and 1990. All patients were female (6-52 years old). Six patients appeared with microscopic hematuria: 3 with episodes of gross hematuria and 3 with mild proteinuria, but none with the nephrotic syndrome. Renal function was normal except for 1 case (52 years old) complicated with hypertension. Serum levels of immunoglobulins and complements were almost normal. Morphologically minor or focal/segmental glomerular alterations were observed. Immunofluorescence showed that pure mesangial IgG deposition was characterized in all cases, whereas no IgA nor IgM was found in any of them. Mesangial deposition of C3 and C1q was observed in 4 and 3 cases, respectively. Electron microscopy revealed dense deposits within the mesangial area in all cases. The clinical course was benign, and the complication with systemic diseases like a rheumatic disease was not observed. This primary glomerulonephritis is an entity characterized by low incidence in Japan, mild abnormalities in urinalysis, minor glomerular alterations with predominant mesangial IgG deposits and a relative benign course. PMID- 8502318 TI - Effect of radiotherapy on peritoneal function in continuous ambulatory peritoneal dialysis. AB - A 25-year-old male patient underwent abdominal radiotherapy following the discovery of lymphadenopathy associated with a testicular teratoma. Prior to treatment, his peritoneal mass transfer area coefficients were within normal limits. One and 2 months after treatment, peritoneal permeability had increased to the extent that continuous ambulatory peritoneal dialysis was rendered impractical. PMID- 8502319 TI - Glomerulonephritis associated with inflammatory demyelinating polyradiculoneuropathy: a case report and review of the literature. AB - A patient developed relapsing inflammatory demyelinating polyradiculoneuropathy associated with nephrotic syndrome. Renal biopsy showed focal-segmental glomerulosclerosis. The review of the literature disclosed that glomerulonephritis with and without nephrotic syndrome seems to be not uncommon in inflammatory demyelinating polyradiculoneuropathy, such as Guillain-Barre syndrome. membranous glomerulonephritis is the most frequent histologic diagnosis while minimal change nephropathy, 'acute glomerulonephritis' and postinfectious type glomerulonephritis are not often present. This is the first case of inflammatory demyelinating polyradiculoneuropathy associated with nephrotic syndrome due to focal-segmental glomerulosclerosis. Larger prospective studies are necessary and may contribute to the understanding of the pathogenesis of both, glomerulonephritis and inflammatory demyelinating polyradiculoneuropathy. PMID- 8502320 TI - Carbamazepine-induced hyponatremia in a patient with partial central diabetes insipidus. AB - A 51-year-old Japanese man was referred for the evaluation of persistent hyponatremia. The serum sodium level remained around 120 mmol/l despite mild water restriction. His past history included chronic alcoholism, myocardial infarction and lumbar disc herniation. Carbamazepine (200 mg, b.i.d.) has been used for more than 8 years for low back pain. Serum sodium returned to normal after carbamazepine was stopped, and rechallenge produced acute symptomatic hyponatremia (117 mmol/l) on day 2 after a total dose of 600 mg. Hepatic, renal and endocrine function were within normal limits, and the response to a water load (20 ml/kg) was also normal. Partial central diabetes insipidus was diagnosed by his response to water restriction and nasal desmopressin administration. Polyuria and hypernatremia were not evident in this case, probably due to a combination of low solute intake and low, but not deficient, levels of plasma ADH. This case demonstrates that carbamazepine may cause acute hyponatremia even in central diabetes insipidus, probably by sensitizing the distal renal tubules. PMID- 8502321 TI - Psychological problems of kidney transplantation: satisfaction with dialysis therapy and desire for transplantation in hemodialysis patients. AB - Psychological problems of kidney transplantation were examined in 275 hemodialysis patients. Desire for transplantation was significantly lower in aged patients than in nonaged cases. The prevalence of alexithymia which is characterized by difficulty in expressing one's feelings and a lack of fantasy and which may be a clinical feature associated with psychological defense mechanisms was significantly higher in aged than in nonaged patients. The results suggest that aged patients tend to suppress the desire for transplantation by means of psychological defense mechanisms such as 'denial' directed toward transplantation and an unconscious pretence of indifference. From the psychological aspect, reconsideration of the quality of life may be required for hemodialysis patients. PMID- 8502322 TI - Absence of glomerulosclerosis in Watanabe heritable hyperlipidemic rabbits. PMID- 8502323 TI - Acute renal failure caused by two single doses of rifampicin with a year of interval. PMID- 8502324 TI - Rupture of double lumen Hickman catheter at time of removal by surgery--another potentially serious complication. PMID- 8502325 TI - Changes in nutritional status of patients with chronic renal failure on a low protein diet. PMID- 8502326 TI - Fatal disseminated Mycobacterium kansasii infection in a hemodialysis patient. PMID- 8502327 TI - Remission of nephrotic syndrome related to AA amyloidosis after hepatic adenomectomy. PMID- 8502328 TI - Interstitial naive and memory T cells in chronic mesangial proliferative glomerulonephritis. PMID- 8502329 TI - Spontaneous jejunal perforation in continuous ambulatory peritoneal dialysis. PMID- 8502331 TI - New predictive protocol for therapeutic treatment of renal and nonrenal anemias with recombinant human erythropoietin with a simple immunoenzymatic dosage of serum burst-promoting activity (IL-3, IL-4, GM-CSF) PMID- 8502330 TI - Influence of recombinant erythropoietin on the production of endothelin-1 from human umbilical artery. PMID- 8502332 TI - Hemodialysis with a new single stable bicarbonate dialysate. AB - A specified stable bicarbonate/glycylglycine dialysate for hemodialysis (HD) analogous to those introduced by us for continuous ambulatory peritoneal dialysis (CAPD) is described. HD with this single dialysate is simple, easy, safe and of reasonable cost. Results obtained from 6 HD patients proved its superiority against acetate dialysate. Bicarbonate/glycylglycine dialysate is also more stable, harmless and easier to use than bicarbonate dialysate prepared on-line. PMID- 8502333 TI - Differentiation of hematuria using a uniquely shaped red cell. AB - Although variously shaped urinary red cells have been reported in glomerulonephritic hematuria, no specific shapes with concrete definition have been proposed. This made morphological differentiation of hematuria vague and caused different results among different observers. To solve these problems and improve the diagnostic rate, we employed a uniquely shaped red cell, which only appeared in glomerulonephritic hematuria, as a probe for diagnosis. We studied 182 hematuria cases from 90 glomerulonephritic patients and 95 hematuria cases from 68 urological disease patients. Fresh urine was collected and observed by differential interference microscopy. The red cell, referred to as G1, has a distinctive doughnut-like shape with blebs and was highly specific for glomerulonephritic hematuria. Occurrence of G1 cells increased at lower pH an higher osmolality of urine. A presence of 5% or more G1 cells could be an indicator of glomerulonephritic hematuria. Specificity and sensitivity of this criterion were 100 and 73%. However, when only acidic concentrated urine (pH < or = 6.4, osmolality > or = 400 mosm/kg H2O) was used, the specificity and sensitivity increased to 100 and 99.2%, respectively. Glomerulonephritic and urological hematuria were correctly diagnosed by counting the urinary red cells with doughnut-like shape in acidic and concentrated urine. This method seems to be superior to others in diagnostic rate, simplicity and clarity. PMID- 8502334 TI - Decreased lithium clearance in patients with hyperthyroidism. AB - Lithium clearance was studied to investigate proximal tubular function in patients with hyperthyroidism (n = 10) and control subjects (n = 7). Patients with hyperthyroidism showed significantly reduced fractional excretion of lithium (FELi) compared with control subjects (15.0 +/- 1.5%, n = 10, vs. 23.7 +/- 0.6%, n = 7, means +/- SE, p < 0.001). The reduced FELi of the hyperthyroid state was reversed toward control values with treatment by antithyroid drugs (12.6 +/- 2.6 toward 26.8 +/- 2.5% for 5 patients, means +/- SE). Tubular reabsorption of phosphate (TRP) was significantly increased in hyperthyroid patients compared with control subjects (96.1 +/- 0.7 vs. 87.5 +/- 0.7%, p < 0.001), and it returned to control values after the treatment. Our data demonstrate that lithium clearance is decreased and TRP is increased in patients with hyperthyroidism, which suggests that proximal tubular reabsorption of sodium and TRP is increased in hyperthyroidism. PMID- 8502335 TI - Urinary tissue plasminogen activator in renal disease. AB - Whereas plasminogen activator of the tissue-type (t-PA) is present in extracts of kidney parenchyma, only small amounts of the enzyme can be detected in normal urine where the major plasminogen activator is of the urokinase-type (u-PA). These observations suggest the existence of physiological or anatomical barriers that effectively confine t-PA to renal tissue and exclude it from the urine. We examined the notion that disease might breach these barriers and so lead to the appearance of abnormal amounts of t-PA in the urine. Under the conditions of the simple fibrinolytic assay that we have developed, urine samples from 30 normal subjects did not contain detectable amounts of t-PA whereas we were able to demonstrate t-PA in samples from 43 of 65 patients with various forms of renal disease. When positive, therefore, tests for the presence of t-PA in human urine provide evidence for renal disease that may not otherwise be apparent. PMID- 8502336 TI - Effect of urea and indomethacin intake on solute excretion in the syndrome of inappropriate secretion of antidiuretic hormone. AB - Our purpose was to compare the effect of urea and indomethacin on solute excretion in hyponatremic patients with inappropriate secretion of antidiuretic hormone (SIADH). In 6 patients (serum Na: 126 +/- 3 mmol/l), the intake of urea (0.1 g/kg) induced a decrease in sodium excretion while urine osmolality, urine flow and osmotic clearance (Cosm) did not change. In the control group, the urinary flow and Cosm were increased as expected, while sodium excretion tended to increase. In the SIADH group, the decrease in the fractional excretion (FE) of Na+ (FE.Na+) (or FE.Cl-) after urea intake was negatively correlated with urinary urea concentration while the FE.K+ was positively correlated with FE.Na+ (or FE.Cl-), which suggests that the effect of urea on sodium excretion takes place proximally to the distal tubule, probably at the thin ascending limb. After indomethacin intake, FE.Na+ (or FE.Cl-), FE.K+, Fe.osm and Fe.urea decreased in the normal and hyponatremic groups. The mean free water reabsorption relatively to osmolar delivery was lower in SIADH (p < 0.05), and did not change significantly after indomethacin intake. The fact that the decrease of FE.Na+ (or FE.Cl-) after indomethacin was associated with a decrease in FE.K+ suggests that the increase in sodium (or chloride) reabsorption occurred more proximally to the distal tubule (probably a the medullary segment of the thick ascending limb of the loop of Henle). PMID- 8502337 TI - Continuous arteriovenous hemodialysis: outcome in intensive care acute renal failure patients. AB - The clinical outcome of continuous arteriovenous hemodialysis (CAVHD), an alternative to continuous arteriovenous hemofiltration (CAVH) in our intensive care units (ICU) in Uppsala, was evaluated for 2 years. Forty-three patients were included. Pretreatment serum urea and creatinine levels (mean +/- SD) were 36 +/- 13 mmol/l and 420 +/- 147 mumol/l, and during treatment, steady-state levels were 25 +/- 10 mmol/l and 333 +/- 120 mumol/l, respectively (p < 0.0001). On top of acute renal failure (ARF), some patients had multiple organ failure that made it necessary to use mechanical respiration (63%), vasopressor drugs (74%) and aortic balloon pump therapy (5%). The outcome of this treatment was 60% when overall survival was considered. Higher dialysate flow rates (i.e., 25 ml/min) were applied in some patients in whom serum urea levels were persistently rising. The result of this was a notable decrease in the urea and creatinine serum levels. From the results of this 2-year experience, we have found CAVHD a promising alternative to CAVH that can be used as a treatment of choice for ARF in critically ill ICU patients. PMID- 8502338 TI - Predictive value of mitral and aortic valve sclerosis for survival in end-stage renal disease on continuous ambulatory peritoneal dialysis. AB - To determine whether mitral valve or anular sclerosis or calcification (MC) is associated with reduced survival in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD), 53 CAPD patients were followed with echocardiography and Doppler echocardiography over 35 months. Both nonsurvivors and survivors with MC had higher systolic blood pressure before CAPD and calcium-phosphorus products during CAPD treatment than patients without MC (p < 0.05). Serum calcium and phosphorus concentrations, alkaline phosphatase and parathyroid hormone activities were higher in nonsurvivors and survivors with than without MC (p > 0.05). Left ventricular end-diastolic and end-systolic volumes were greater (p < 0.01), ejection fractions were smaller (p < 0.05) in nonsurvivors with than without MC, but not in survivors with versus without MC. Severe MC and grade III mitral valve regurgitation were more frequent in nonsurvivors than in survivors (p < 0.03). No valvular stenoses were found. It is concluded that the development of MC is favored by long-standing predialysis arterial hypertension and by high calcium-phosphorus products during CAPD. Nonsurvivors with MC are characterized by reduced systolic left ventricular function or severe valvular lesions. A close cardionephrologic cooperation is necessary to improve the survival of CAPD patients with these risk factors. PMID- 8502339 TI - Early detection of diabetic nephropathy and criteria for the initiation of therapy. AB - In 86 patients with non-insulin-dependent diabetes mellitus who were negative for proteinuria by a test paper method, the albumin excretion rate was compared to the albumin/creatinine ratio, and a baseline albumin/creatinine ratio value was determined at which therapy to arrest the progression of nephropathy should be initiated. The albumin excretion rate, albumin/creatinine ratio, and urinary creatinine excretion were determined from urine samples obtained at outpatient visits. The reproducibility of time-restricted urine sampling was investigated using the creatinine excretion rate. The mean coefficient of variation was found to be 42%, and inaccurate urine sampling appeared to cause variation in the albumin excretion rate. A significant difference was evident between males and females in creatinine excretion (0.823 +/- 0.152 mg/min for males and 0.577 +/- 0.182 mg/min for females, p < 0.001). The baseline albumin/creatinine ratio value for initiating therapy was established to be 36 mg/g creatinine for males and 51 mg/g creatinine for females. Use of the albumin/creatinine ratio appears to provide a simple and valuable index for determining when to initiate therapy for diabetic nephropathy. PMID- 8502340 TI - Renal function impairment in workers previously exposed to cadmium. AB - Cadmium-induced renal effects were followed (1989) in 16 workers previously exposed to cadmium, who had been shown 5 years earlier to have had tubular damage; all but 1 worker had persistent tubular damage (beta 2-microglobulin > 60 micrograms/mmol creatinine). The mean glomerular filtration rate (GFR) decreased from 77.3 to 71.7 ml/min/1.73 m2, which is 2.0 ml/min more than would have been expected from aging only. There was a negative correlation between loss of tubular function (relative clearance of beta 2-microglobulin) and the ratio of observed versus reference GFRs in accordance with a 1984 study. The results confirm that cadmium-induced tubular damage is irreversible. They also suggest that the glomerular dysfunction after cadmium exposure is irreversible and progressive also after exposure stops. A nonsignificant correlation was found between cumulative cadmium exposure and decreased GFR. PMID- 8502341 TI - Serum glycated albumin and fructosamine in renal dialysis patients. AB - The effect of uraemia on protein glycation was studied by measuring glycated albumin and fructosamine in 50 non-diabetic dialysis patients (31 continuous ambulatory peritoneal dialysis, CAPD, 19 haemodialysis). After correction for serum albumin concentration, glycated albumin (g/100 g) was increased in the haemodialysis group (1.94 +/- 0.40) compared with both CAPD patients (1.46 +/- 0.37; p < 0.001) and controls (1.52 +/- 0.29; p < 0.001), but did not differ between CAPD patients and controls (p > 0.05). Serum fructosamine, corrected for either serum albumin or total protein concentration (mumol/100 g), was raised in CAPD (828 +/- 90, 386 +/- 41, respectively) and haemodialysis patients (802 +/- 123, 391 +/- 42, respectively) compared with controls (609 +/- 69, 332 +/- 27, respectively; p < 0.0001 in all cases), but did not differ between the two dialysis groups (p > 0.05). A single haemodialysis cycle had no effect on the measurement of glycated albumin or fructosamine (p > 0.05). The results confirm that glycated protein levels are generally raised in dialysis patients. In CAPD patients, altered albumin metabolism resulting from large peritoneal losses is likely to have caused a decrease in the amount of albumin glycated, an effect less apparent on the concentration of fructosamine because of the additional contribution of glycated globulins. PMID- 8502342 TI - The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of skeletal muscle in patients with chronic renal failure treated by regular hospital haemodialysis. AB - The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of the anterior tibialis muscle was studied in 10 patients with chronic renal failure treated by regular haemodialysis. Repeat muscle biopsies taken when the target haemoglobin concentration of 11 g/dl was achieved showed an increase in median glycogen content from 35 mg/g fat-free dry muscle to 51 mg/g (p < 0.05). The histological appearance showed a marked improvement in muscle fibre diameters, in particular for the type I fibres and a reduction in cytoarchitectural abnormalities. These changes would be expected to produce an increase in both muscle strength and performance and are most probably a consequence of an increase in muscle oxygen delivery. PMID- 8502343 TI - Bacteremia in patients on chronic hemodialysis. A multicenter prospective survey. AB - A prospective epidemiologic survey of bacterial infections in chronic hemodialysis patients was conducted from September 1, 1989 to February 28, 1990 in 27 dialysis units. Of the 1,455 patients enrolled in the study, 55 presented 63 episodes of bacteremia (incidence of 0.7 bacteremia per 100 patient-months). The portal of entry of sepsis was the vascular access in 50.8% of the episodes. The causative microorganisms were most often gram-positive cocci (69.8%). 23% of the teremic patients had a serum ferritin > 1,000 micrograms/l versus 7% of the nonbacteremic infected patients (p = 0.005). 39.7% of the patients had undergone a surgical operation during the month preceding the bacteremia. Eight patients had a recurrence during the study period and 8 had a metastatic localization: spondylodiscitis 2, septic pulmonary embolus 2, endocarditis 1, arthritis 1, liver abscess 1 and endophthalmia 1. 66% of the episodes required a hospitalization that lasted an average of 20 days. Mortality rate was 6.3%. This prospective study showed a trend towards a reduction in incidence and mortality of bacteremia in patients on chronic hemodialysis. PMID- 8502344 TI - [Candidal bezoar of the urinary tract during Candida albicans septicemia]. AB - We report a case of an obstructing fungus ball of the urinary tract. Typical predisposing factors were present, i.e. bladder catheter, vesico-ureteral reflux, urinary infection, parenteral nutrition, prolonged antibiotherapy, hyperglycemia. Candida albicans septicemia was noted. Diagnosis was made by percutaneous nephrostomy under echographic control allowing urinary sampling (C. albicans) and anterograde pyelography showing an ureteral stenosis. Urinary drainage and local and general administration of amphotericin lead to a complete resolution of the fungus ball and the systemic candidiasis. PMID- 8502345 TI - [T lymphocyte activation induced in vivo in different strains of mice after injection of anti-CD3 antibodies: prevention by an anti- TNF antibody]. PMID- 8502346 TI - [New aspects of extracellular space regulation by aldosterone]. PMID- 8502347 TI - [Current concepts on the alloreactive response]. AB - Many new data have been obtained in the last 4 years about the structure and the functions of Major Histocompatibility Complex (MHC) molecules. Structural data are summarized and the functions of MHC molecules in the presentation of peptides to T cells is described. The high selectivity of peptides binding to MHC molecules is explained. The negative and positive selection of T cells in the thymus is described and the notion of repertoire introduced. The consequences of these new data on the understanding of H2 restriction and alloreactivity are explained. The 4 potential types of alloreactivity are defined: 1) House keeping gene (HKG) peptides bound to allogenic MHC molecules, 2) allogenic peptides (derived from allogenic MHC molecules) bound to allogenic MHC molecules, 3) empty allogenic MHC molecules, 4) allogenic peptides bound to autologous MHC molecules. In fact, the allogenic response is mostly directed toward HKG peptides bound to the allogenic MHC molecules of the graft cells (type 1). The potential role of type 4 alloreactivity in rejection is discussed. PMID- 8502348 TI - [Endothelin and kidney]. AB - Endothelial and epithelial cells release a potent 21-residue peptide, endothelin (ET) which is an endothelium-derived-contracting-factor (EDCF). The peptide causes contraction of vessels and induces sustained blood pressure elevation. Beside its role in the vasoconstriction ET has strong inotropic effect on the myocardium and induces smooth muscle cells contractions. Renal actions, similar to angiotensin and norepinephrine, focus on its potential importance in nephrology. Acute and chronic renal failure showed increased plasma and urinary ET levels. An understanding of the regulation of the release of ET may provide knowledge about the pathogenesis of acute renal failure, the progression of chronic renal failure and cyclosporin A induced toxicity. Further research is needed to substantiate the new and promising perspective of ET in human diseases and therapy. PMID- 8502349 TI - [Cough headache and vertigo as symptoms of the Arnold-Chiari syndrome]. AB - Headache with paroxysmal vertigo were induced by cough in a case of the Arnold Chiari type I malformation. The authors suggest that exertional headache and posterior cranial fossa symptoms of unclear aetiology may indicate presence of the syndrome, and the availability of magnetic resonance imaging made possible the detection of the malformation. PMID- 8502350 TI - [Acute hyponatraemic encephalopathy in a patient on chronic hemodialysis program - a case report]. AB - By the end of a dialysis session the patient had a generalized convulsive seizure. Then meningeal syndrome, right-sided hemiparesis with central lesion of right facial nerve and bilaterally positive extensor plantar response were found. Because of the increase of blood pressure and then increased body temperature the diagnosis of acute hyponatraemic encephalopathy was not made only on the basis of the plasma ionogram (Na+ 110mEq/1) but also after excluding possible subarachnoid haemorrhage and acute cerebrospinal meningitis and encephalitis by cerebrospinal fluid examination. Hyponatraemia found in some patients suffering from chronic renal insufficiency is increased by haemodialysis session. Cerebral oedema which is proportional to natraemia is caused by urea disolation from intracellular to extracellular fluid. This process increases concentration gradient between intracellular and extracellular fluids. The perceptible neurological signs occur as natraemia declines below 120 mEq/l. PMID- 8502351 TI - [Two cases of colloid cysts of the third ventricle with nasal rhinorrhea]. AB - The authors present 2 cases of tumours of third ventricle with intracranial hypertension and cerebrospinal fluid rhinorrhea. The cause of the CSF rhinorrhea most often was thinning of lamina ethmoidalis and dura mater and rarely intussusception of arachnoidea into the intrasellar space in patients with oval orifice for the stalk of pituitary body due to prolonged intracranial hypertension. Efficacious treatment of CSF rhinorrhea comprises not only removing of the tumor but also introducing the valve and in some cases tightening of the base of the anterior and middle fossa. PMID- 8502352 TI - [A case of acoustic neurinoma in a girl aged 13]. AB - A 13-year-old girl with large richly vascularized acoustic neurinoma is reported. The family history and clinical evidence failed to suggest neurofibromatosis in the family. The clinical syndrome included paroxysmal headaches, vertigo, loss of consciousness and left ear hearing loss. The application of Nd-YAG laser during the operation reduced bleeding and enabled radical removal of the tumour. PMID- 8502353 TI - [A case of lumbar glomeruloma]. AB - A case of the patient with atypical localization of glomus tumor in lumbar region is reported. Trigger pain of unusual intensity resistant to pharmacological treatment ceased immediately after the operation. PMID- 8502354 TI - [ Selegiline (Jumex) in the treatment of narcolepsy]. PMID- 8502355 TI - [The effect of the neck rotation test on auditory evoked brainstem potentials in healthy subjects]. AB - The purpose of the study was to assess the effect of neck rotation test on the pattern of brainstem auditory evoked potentials in healthy subjects. The study was carried out on 40 healthy subjects aged 19-26 years using a Neuromatic 2000 C device of Dantec, by the generally accepted method. The records were taken with the patient in lying position with head in neutral position and during head rotation through 60 degrees to the right and then to the left side. A click stimulus was fed into the tested ear, its frequency was 10 Hz and it was repeated 2000 times. The filters used were 100 Hz-2 kHz. The records obtained during neck rotation showed that the latency times of various waves were slightly prolonged on the side of the rotation (but were still within normal limits), while on the contralateral side they were similar to those in normal position. Moreover, neck rotation to the right or to the left side caused a bilateral slight shortening of the latency time (in absolute values) between waves I-III, at the expense of slight prolongation of this time between waves III-V which was still within the variability range of the normal values. PMID- 8502356 TI - [The effect of neck rotation on auditory evoked brainstem potentials in patients with degenerative cervical spine changes]. AB - Using the neck rotation test during recording of auditory brainstem evoked potentials the authors examined 60 subjects aged 16-60 years, including 20 healthy ones and 40 with cervical spondylarthrosis. The Neuromatic 2000 C Dantec device was used. Half the patients with cervical spine changes had also receptive hearing damage of low degree. The study demonstrated that neck rotation affected the latency time of the analysed waves I and II. The time was significantly prolonged in the patients with spondylarthrosis. The authors believe that simultaneous prolongation of the mean latency between waves I-III suggests worse compensation of circulation in patients, especially in the initial part of the auditory pathway. The authors think that the neck rotation test could be used in the study of brainstem auditory evoked potentials as a challenge test. PMID- 8502357 TI - [Trials of monosialoganglioside (Sygen) treatment in ischemic stroke]. AB - 65 patients with ischaemic stroke were treated for 6 weeks by intramuscular injections of Sygen--monosialoganglioside 40 mg daily. The results were double blinded and compared with those in placebo group (Vitamin PP). The results evaluated by Mathew scale did not show any significant differences between both groups. However in the Sygen group we have noticed more patients with very good therapeutic results (almost complete recovery of functions). Immunological studies have not revealed any reaction, which may be considered as a result of allergogenic action of monosialoganglioside. PMID- 8502358 TI - [The effect of azathioprine treatment on IgG subclasses in multiple sclerosis]. AB - IgG and its subclasses: IgG1, IgG2, IgG3 and IgG4 were determined in the CSF and sera from 20 patients with multiple sclerosis before and after treatment with azathioprine. The effect of the treatment on IgG and IgG subclasses intrathecal synthesis was studied as well. There was a decrease in IgG level in the CSF of MS patients after the treatment with azathioprine. This was mainly due to the decrease of IgG1 and IgG2 subclasses levels. There was no evidence of the influence of azathioprine treatment on IgG and its subclasses levels in MS sera as well as on IgG and IgG subclasses intrathecal synthesis. PMID- 8502359 TI - [ Ceftriaxone (Rocephin "Roche") in short-term program of perioperational prophylaxis in neurosurgery]. AB - Own experience is presented in the administration of prophylactic antibiotic treatment in clean neurosurgical operations. The clinical material comprised 131 patients subjected to 138 operations. For prophylaxis ceftriaxone (Rocephin "Roche") was given by the so called short term programme in which 2 g of the drug was given intravenously before the operation, and 1 g after 24 hours. The frequency of postoperative infections was 0.7% in the group. The effectiveness is stressed of the short-term programme of prophylactic antibiotic treatment in the prevention of postoperative infections in neurosurgery emphasizing that operations in emergency cases, perioperative steroid therapy, tumours, craniotomy with free bone flap do not reduce the effectiveness of the method. PMID- 8502360 TI - [Lateral ventricle choroid plexus papillomas in infants]. AB - Choroid plexus papillomas are rare intracranial tumours occurring most frequently in children. In the period 1983-1988 in the neurosurgery department 10 infants were treated for choroid plexus papillomas. Their age was from 4 weeks to 12 months. The diagnosis was based on the results of ultrasonography and CT. Eight patients had shunts implanted for hydrocephalus. In most cases the histological examination demonstrated benign tumours. Radical removal of the lesion was done in 90% of cases, but, despite this, remote results were satisfactory in only 40% of cases. PMID- 8502361 TI - [Treatment of medulloblastomas in children]. AB - Fifty-two children were treated surgically in the years 1980-1987. Their mean age was 5.3 years, range 10 months-13 years. In 58% partial removal of the tumour was done, in 4% only biopsy was performed. Shunt treatment was necessary in 40% cases. The analysis showed that in the cases treated in the years 1980-1984 1 year survival was 75%, 3-year survival was 39%, 5-year survival was 25%. Statistical analysis demonstrated that in the cases treated in the years 1985 1987 the 1-year survival was 95%, 3-year survival was 60%, and 5-year survival was 51%. PMID- 8502362 TI - [Diagnosis and treatment of brain abscesses in children]. AB - Fourty children were treated for brain abscess in the period 1983-1988 at the Neurosurgery Department, Children's Health Centre, Warsaw. Their age was from 4 weeks to 16 years. In 38 cases the treatment was surgical, followed by antibiotic therapy, in 2 cases only antibiotics were given. In 7 cases shunts were implanted for treatment of hydrocephalus developed in infants. Two patients died during the treatment. Problems encountered in various methods of brain abscess treatment are discussed. PMID- 8502363 TI - [Prevention of infection in neurosurgery]. AB - The dangers connected with postoperative wound infection, especially in neurosurgery, are discussed, together with various methods of reduction in the pertinent literature and used in various clinical centres. The review shows that properly used perioperative prophylaxis has reduced markedly the incidence of wound infection, even to zero in elective clean neurosurgical operations. The antibiotics used for this purpose are described, and indications are given concerning the selection of proper antibiotics. PMID- 8502364 TI - [Changes of blood flow velocity in the extracranial and basilar arteries in physiological aging]. AB - The maximal blood flow velocity was assessed in extracranial and cephalad arteries: ophthalmic, supratrochlear, common carotid, superficial temporal, subclavian and vertebral in 150 clinically healthy subjects aged 18 to 80 years using continuous ultrasound 5 MHz wave. In all the arteries the flow velocity was decreasing with age. The degree of velocity decrease varied between various arteries, especially in the common carotid and subclavian arteries, less so in the ophthalmic and vertebral arteries, and least in the supratrochlear and superficial temporal arteries. In a small number of cases the maximal systolic velocity was very low in the supratrochlear and ophthalmic arteries although this velocity and the neurological status were normal in these subjects. PMID- 8502366 TI - [Epilepsy in a child with ring chromosome 14]. AB - A case of epilepsy in a child with ring chromosome 14 is presented. The typical features for the ring chromosome 14 syndrome in 5 years old girl i.e. psychomotor retardation, microcephaly, generalized hypotonia and some dysmorphism were found. Photoanthropometric method by Stengel-Rutkowski et al. for better estimate of dysmorphic pattern was used. It made possible to ascribe the features to partial deletion of the long arm segment of chromosome 14. Computer tomography revealed brain atrophy. PMID- 8502365 TI - [A rare case of dissemination of anaplastic oligodendroma outside the central nervous system]. AB - A rare case is reported of primary brain tumour with histological features of anaplastic oligodendroglioma, with metastases outside the central nervous system. Of interest is a short remission after treatment with cyclophosphamide and vepesid which shows that this type of tumour is sensitive in a way to chemotherapy. PMID- 8502367 TI - Attentional interaction in the split-brain: evidence from negative priming. AB - Negative priming refers to an inhibitory effect, in which responding is slower when an attended target is identical, or related to a previously ignored distractor. It has been suggested that the processes underlying this effect are important for maintaining attentional focus and orientation. A version of this paradigm, in which subjects attended to digits presented to the RVF, and ignored digits presented to the LVF was employed with two split-brain subjects and seven normal controls. The task was to categorize RVF digits as odd or even. Each of the split-brain patients showed significant amounts of negative priming from ignored LVF distractors, as did the normal control subjects. It is concluded that even in the split-brain there are rich attentional interactions with respect to complex attributes encoded within each hemisphere. It is suggested that these rely on interaction between cortical and subcortical processing, and may play an important role in relation to the unified and apparently well integrated behaviour of commissurotomy patients in everyday settings. PMID- 8502368 TI - Left-handedness and old age: do left-handers die earlier? AB - Data are presented on the prevalence of current left-handedness and prior left handedness (switched) in 2787 subjects from 21 to 101 years of age. In addition, data on sex differences, familial sinistrality, hand posture when writing, and education were recorded. Two hypotheses were tested. The elimination hypothesis states that reduced frequency of left-handers in old age is due to reduced longevity. The modification hypothesis states that differences in the number of left-handers between older and younger persons are due to changing patterns of social norms. The results showed a decreasing prevalence of left-handedness across the age span, with 15.22% in the youngest group (21-30 years), but only 1.67% in subjects older than 80 years. There was however a corresponding increase in the number of subjects who had switched hand for writing, 2.69% in the youngest group to 6.75% in subjects 80 years and above. This supports the modification hypothesis and questions the elimination hypothesis. However, the mean percent score was still lower in subjects above compared to below age 40 after correction for hand switching. Thus, although changes in social norms towards left-handers seem to be the most likely explanation, we have not empirically disproved the elimination hypothesis. PMID- 8502369 TI - Monitoring of general knowledge: evidence for preservation in early Alzheimer's disease. AB - The ability to retrieve and monitor factual information was examined in normal old adults and patients with a mild Alzheimer's disease (AD). Subjects were given free recall and multiple-choice recognition tests of 48 general knowledge questions. For both tests, subjects made confidence ratings regarding the certainty of their answers, and they also made feeling-of-knowing ratings for those questions they did not answer in recall. Results indicated a superiority of controls over patients in recall that was somewhat reduced in recognition. However, there were no group differences in any of the slopes relating rating to accuracy: recall and recognition as a function of confidence rating, and recognition of questions not answered in recall as a function of feeling-of knowing. This pattern of outcome indicates that early AD is associated with a deficit in fact-retrieval, although the ability to monitor stored general knowledge may be intact. PMID- 8502370 TI - Dynamic gender-related differences in dichotic listening performance. AB - This experiment investigated dynamic gender-related differences in perceptual asymmetry (PA) in a dichotic task. Twenty right-handed males and 20 right-handed females performed a 200 trial directed attention dichotic listening task using consonant-vowel-consonant nonsense syllables. Men showed a greater right-ear advantage (REA) at the beginning of the test than did women. Over the course of the test the REA in men declined significantly (P < 0.001) whilst in females the REA showed a significant increase (P < 0.001). Thus by the end of the test the REA was greater in females than males. However, the reduced REA in males was entirely due to improved left-ear (LE) performance and the increased REA in females was due to improved right-ear (RE) performance. The change in PA in women is consistent with a dynamic improvement in left hemisphere (LH) syllable processing and in men a dynamic improvement in the transmission of information through the right hemisphere (RH) to the language processing areas in the LH. PMID- 8502371 TI - Hand preference and the incidence of accidental unilateral hand injury. AB - Four hundred and eighty-six individuals gave detailed descriptions of an accidental unilateral hand injury and answered questions about their hand preference. Their handedness data were compared to 402 respondents (matched for sex and age) with no experience of hand injury. The risk of hand injury was similar for right- and left-handers. Individuals with consistent hand preference, regardless of side, were more likely to injure their preferred hand when compared to mixed preference types. The present data argue for a use explanation of hand injury risk (one is more likely to injure the hand that is used most frequently) rather than an explanation based on inherent risk factors present for left- but not for right-handers. PMID- 8502372 TI - Capture errors and sequencing after frontal brain lesions. AB - This study addresses the effect of strong routine associations (capture errors) in hindering the control of on-line serial or sequencing tasks. Patients with focal frontal lobe lesions were significantly inferior to normal control subjects and patients with posterior brain lesions, when conditions that may lead to capture errors were present. The results suggest that the primary dysfunction exhibited by patients with frontal lobe lesions on capture error tasks may lie not in the disengagement from the invalid associations but in focusing attention to alternative strategies of response. PMID- 8502373 TI - Cognitive brain potentials in a three-stimulus auditory "oddball" task after closed head injury. AB - Event-related potentials (ERPs) were recorded in a three stimulus oddball task from 16 patients who had sustained a severe closed head injury at least 6 months before testing, and from 16 control subjects. The stimuli comprised a random sequence of frequent non-target tones (P = 0.70), rare target tones (P = 0.15), and rare novel sounds (P = 0.15). The task requirement was to respond promptly to each target tone. From a latency of 200 msec onwards, the ERPs evoked by frequent non-targets were substantially more negative-going in the head-injured than in the control group. When this difference in the ERPs to the frequent tones was taken into account, there was no evidence to suggest that either the latency or the amplitude of the target-evoked N2 and P3b components differed between the groups. The novel stimuli evoked a prominent P3a component. The amplitude and scalp distribution of this component differed little between the groups, but its peak latency was reliably longer in the head-injured subjects. The findings in respect of the N2 and P3b components suggest that impairments in early processing of task-relevant stimuli are not an invariant feature of closed head injury. The findings regarding P3a suggest that, in the majority of patients, head injury has only a limited effect on the neural systems underlying involuntary shifts of attention. PMID- 8502374 TI - Temporal dissociation of the prehension pattern in Parkinson's disease. AB - This study assesses the reach to grasp movement of eight Parkinson and eight control subjects. The reach was of either 15, 27.5 or 40 cm. The grasp was either of a small (0.7 cm) or a large diameter (8 cm) dowel. When comparing Parkinson to control subjects, no differences were found in the regulation of movement parameters according to changes in object distance or size. However, for Parkinson's disease patients the onset of the manipulation component was delayed with respect to the onset of the transport component. It is proposed that this reflects a deficit in the simultaneous or sequential implementation of different segments of a complex movement. PMID- 8502375 TI - Normal forgetting, impaired acquisition in memory for complex naturalistic scenes by fornix-transected monkeys. AB - As part of an earlier experiment three rhesus monkeys (Macaca mulatta) with fornix transection and three normal control monkeys had learned to discriminate among 320 naturalistic complex scenes. The fornix-transected animals had been much slower than the controls to reach criterion in learning this task, but eventually did so. The present experiment measured long-term forgetting of these scenes. Seven weeks after reaching criterion each animal was retested. All animals showed some forgetting of the scene discriminations they had learned. The amount forgotten was equal in the two groups. These results show that the slower learning of the scenes following fornix transection was not caused by accelerated forgetting. The present findings in fornix-transected monkeys are similar to previous findings in human amnesic patients. PMID- 8502376 TI - Impaired cognitive shifting in parkinsonian patients on anticholinergic therapy. AB - In this study we established that cognitive shifting, an ability that is known to be affected in PD, is more impaired in PD patients, treated with anticholinergics, than in de novo patients. Eleven PD patients on anticholinergic monotherapy were compared with 30 de novo patients. The groups did not differ with respect to age, duration and severity of PD, and depression, nor with respect to general intelligence or attention. We assessed cognitive shifting with three different card-sorting tests. The patients on anticholinergics showed a poorer performance on all card-sorting tests than the de novo patients did. The patients on anticholinergics needed significantly more trials in two card-sorting tests and discovered significantly less categories in total. There was also a significant difference in memory performance, but memory performance did not correlate with any score on the card-sorting tests. This indicates that the performance on card-sorting tests and the memory performance were independent. PMID- 8502377 TI - Event-related potentials in high-functioning adult autistics: linguistic and nonlinguistic visual information processing tasks. AB - Event-related potentials (ERPs) were recorded from high-functioning adult autistics and age- and IQ-matched normal controls during performance of two non linguistic information processing tasks, the Continuous Performance Task (CPT) and Span of Apprehension (SPAN), and an Idiom Recognition Task (IRT) involving idiomatic, literal and nonsense phrases. The autistics exhibited behavioral deficits only when attempting to identify idiomatic phrases. The ERP correlate of that deficit was greatly reduced N400 to idioms. In addition, autistics produced larger N1 amplitudes in all tasks, and larger P3s in the IRT and CPT. PMID- 8502378 TI - Single-character processing in a case of pure alexia. AB - The processing of single characters in a pure alexic patient was studied in an attempt to identify the impairment responsible for his reading disorder. Observations from Experiments 1 to 4 suggested a deficit of identification of alphanumeric stimuli without any impairment affecting the elaboration of a structural description of visual stimulation. Experiment 5 indicated that the identification disorder results from a defect in the selective processes- activation and/or inhibition--that must come into play for achieving an appropriate match between a structural description of the stimulation and representations of the identities of known stimuli. The possible implications of this deficit in single-character identification for word reading are discussed. PMID- 8502380 TI - Career choice and handedness: a survey among university applicants. AB - By means of the Edinburgh Handedness Inventory the patterns of handedness were studied in 16,590 applicant students to several professional courses in a Brazilian university. The distributions of the laterality quotient (LQ) were different for male and female students, with more left-handers found among the males. The LQ's distributions were different for applicants to distinct courses or to blocks of related occupations. However, no differences were observed between left- and right-handers when each sex was studied separately. No statistically significant differences in handedness were found among the students of different courses that were accepted by the university. PMID- 8502379 TI - Changes in visuospatial attention over the adult lifespan. AB - Shifts of visual attention elicited by spatial cues were examined for detection and letter-discrimination tasks in 90 normal adults ranging in age over each decade from the 20s to the 70s. Spatial cues were valid, invalid, or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus onset asynchrony (SOA) between cue and target was varied between 200, 500 and 2000 msec. Reaction time (RT) costs and benefits associated with spatial cueing did not vary with age for: (1) the detection task; (2) the letter-discrimination task with peripheral cues; and (3) the letter-discrimination task with central cues at a short (200 msec) SOA. RT costs and benefits increased with age only for SOAs greater than 200 msec with central cueing in the discrimination task. In general, the efficiency of cue-based shifts of visuospatial attention appears relatively resistant to the effects of adult age up to 79 years. When an age effect was found, RT costs and benefits increased steadily across all age decades, the correlation with age being 0.25 and 0.38 for the 500 and 2000 msec SOAs, respectively. The findings suggest a qualitative difference in the influence of normal adult aging and effects of dementia noted in previous studies; normal aging has only a weak influence on voluntary attention shifts, whereas dementia affects both voluntary and involuntary modes of attention shifting. PMID- 8502381 TI - Do ear advantage scores obtained in a consonant-vowel recall test vary with respect to the required response condition? AB - A dichotic test of monosyllabic CV syllables was administered three times to 56 male right handers and 50 male left handers. During each experimental session the subjects had to perform this dichotic test using a different response condition. On one occasion they were required to verbally report the perceived syllables (speak condition), on another occasion they were asked to write down the syllables they had heard (write condition), and lastly, they were asked to visually recognize the stimuli (visual condition) which were presented onto a monitor screen. The aim of the experiment was to check whether the dichotic test results differ with respect to the required response condition. It was found that ear advantage scores were not influenced by the response condition. PMID- 8502382 TI - Current concepts of migraine pathogenesis. AB - Migraine is a neurovascular reaction to sudden changes in the internal or external environment. Each individual has a hereditary "migrainous threshold," with the degree of susceptibility depending on the balance between excitation and inhibition at various levels of the nervous system. The mechanism of migraine has been presented as an unstable trigeminovascular reflex with a segmental defect in the pain control pathway. This defect permits excessive discharge of part of the spinal nucleus of the trigeminal nerve and its thalamic connections in response to excessive afferent input or corticobulbar drive. The end result is the interaction of brain stem and cranial blood vessels, with the afferent impulses from the latter creating the throbbing (pulsating) character of the headache. Diffuse projections from the locus ceruleus to the cerebral cortex could initiate cortical oligemia and possibly spreading depression. Activity in this system could account for the migrainous aura that may occur quite independently of the headache. The headache phase may be interrupted by therapy aimed at either the central or peripheral end of the trigeminovascular afferent pathway. Strong evidence suggests that serotonin (5-hydroxytryptamine, 5-HT) plays an important part in the genesis of migraine. Whether 5-HT is effective in central pain control pathways, the serotonergic projection to the cerebral cortex, its direct action on the cranial blood vessels, or its action at all three sites remains uncertain. It seems probable that the 5-HT agonists act to terminate migraine through the cerebral and extracranial circulations, whereas medications used for prophylaxis may act centrally. PMID- 8502383 TI - Central neurogenic mechanisms of migraine. AB - Evidence obtained from clinical studies, magnetoencephalography, and 31P magnetic resonance spectroscopy indicates that spreading depression is the underlying basis of migraine aura. Magnetoencephalographic and 31P magnetic resonance spectroscopic evidence also exists to explain interictal central neuronal hyperexcitability in migraine sufferers. A low intracellular brain magnesium concentration may be the link between the physiologic threshold for migraine and the attack itself. PMID- 8502384 TI - Chronic refractory headache. AB - Approximately 40% of patients seen in major headache clinics suffer from chronic daily headache. Of a series of 630 patients with chronic daily headache, 489 were diagnosed with transformed migraine, 84 with chronic tension-type headache, and 57 with new daily persistent headache. Of these patients, 73% overused symptomatic medication, particularly analgesics and ergotamine, and as a result, suffered from drug-induced headache or rebound headache. PMID- 8502385 TI - Migraine in the United States: a review of epidemiology and health care use. AB - According to the American Migraine Study, 17.6% of females and 6.0% of males in the United States currently suffer from severe migraine. These findings are based on the responses of more than 20,000 people to a self-administered questionnaire mailed to respondents. The study reveals that migraine prevalence varies according to age, gender, and income. Despite high rates of headache-related disability, the study also shows that most people with migraine have never been diagnosed by a doctor or treated with prescription medications. To improve diagnosis and treatment of migraine, public health interventions are indicated. PMID- 8502386 TI - Insulinoma and meals ready to eat. PMID- 8502387 TI - Permission granted. PMID- 8502388 TI - Electromagnetic pulse (EMP), Part II: Field-expedient ways to minimize its effects on field medical treatment facilities. AB - Part I of this paper showed that a field commander can expect approximately 65% of his unprotected electronic medical equipment to be damaged by the electromagnetic pulse (EMP) from a single nuclear detonation as far as 2200 km away. Using computer modeling, field-expedient ways to minimize the effects of EMP were studied. The results were: (1) keep wiring near the ground, (2) keep wiring short, (3) unplug unused equipment, (4) run power cabling and tents in a magnetic north-south direction (avoid running power cabling in the east-west direction), and (5) place sensitive equipment in International Organization for Standardization shelters. PMID- 8502389 TI - Patient care outcomes: implications for the Military Health Services System. AB - Policy makers are targeting patient outcomes and the effectiveness of interventions as possible ways to curb spiraling health care costs. Quality assurance/improvement programs are focusing on patient outcomes as a way to evaluate and improve care delivery. Consequently, members of the Military Health Services System need a solid understanding of the current emphasis on the outcomes of care to be knowledgeable participants in the health care changes precipitated by highlighting patient outcomes. PMID- 8502390 TI - The effect of command emphasis and monthly physical training on Army physical fitness scores in a National Guard Unit. AB - Individual fitness, an important component of combat readiness, has been found to be deficient in some Reserve Component units of the United States Army. We evaluated a program of monthly physical training in an environment of increasing emphasis on unit physical fitness in an effort to determine the effect on unit performance on the semi-annual Army Physical Fitness Test (APFT). This program was examined in a retrospective manner to establish its effectiveness over a 6 month period. No statistically significant improvement in APFT scores could be found over the course of the study, suggesting that such a program is not an efficient means of improving unit fitness in the Reserve Components of the United States Army. PMID- 8502391 TI - A case study of a coordinated care program: development and implementation of Fort Sill's Catchment Area Management Project. AB - One of the Department of Defense's initiatives to contain costs of the Civilian Health and Medical Program of the Uniformed Services is the Catchment Area Management (CAM) Demonstration Project. CAM's fundamental coordinated care concept is to contain the military's health care costs by granting the military treatment facility (MTF) commander full clinical and fiscal responsibility for the health care of all beneficiaries within the MTF's catchment area. This article describes the CAM Demonstration Project at Fort Sill during its developmental and implementation phase from June 1989 to April 1991. The six operational goals of the CAM Project are identified and discussed. Additionally, nine essential lessons learned are briefly reviewed. PMID- 8502392 TI - Fort Polk Heart Smart Program. Part I: Background design and significance. AB - This paper introduces three cardiovascular health evaluation and promotion projects targeting military families at Fort Polk, Louisiana. These studies examine dietary behavior and life-styles including tobacco and alcohol use of military wives, physical activity, cardiovascular disease risk factors of military personnel and their families, and other behavioral profiles with the goal of developing a healthy lifestyle modification program for families. Relevant biomedical background and rationale considerations are developed to support the current research. In addition, conclusions drawn from these studies indicate the opportunity for future health promotion programs at other military installations. The studies will provide the background for a manual of operations to conduct health promotions for families on a military base. Further, the model provides the opportunity for a social support mechanism for families during times of stress and military operations. PMID- 8502393 TI - Fort Polk Heart Smart Program. Part II: Cardiovascular risk factor assessment. AB - In order to identify potential abnormalities, a cardiovascular risk-factor screening was developed as part of the Fort Polk Heart Smart Program. Serum lipids and lipoproteins, blood pressure, and selected anthropometric indices were measured on 703 individuals. Overweight was more a problem for females, with over 40% having a body mass index greater than 27. The percentage of subjects exceeding National Cholesterol Education Program guidelines increased with age. Some 30% of white men 30-39 years old and 60% of white men above 40 years old had elevated total cholesterol. These observations provide the basis for a health promotion program for young military families. PMID- 8502394 TI - Fort Polk Heart Smart Program. Part III: Assessment of dietary intake of military wives. AB - Dietary intake of military wives and factors that influence nutrition of military families were examined in 186 military wives--67% white, 18% black, 11% Hispanic, and 4% other. The ages ranged from 19 to 45 years (mean = 28.7 years). The observations show that 1.7 meals per day were shared by all family members. Due to differences in energy intake and RDAs by age, dietary intakes were assessed in two age groups: 19-24 years (N = 51) and 25-45 years (N = 135). For both age groups, total energy intakes were lower than the RDAs, and the dietary composition was 52% carbohydrate (CHO), 14% protein, and 34% fat. Military wives 25-45 years old consumed more CHO in the form of sugar compared to the younger wives, who consumed more CHO in the form of starch. Some families require food stamps and are in the WIC program. There were no age differences in the type of protein or fat consumed, averaging 66% animal protein and 12% saturated fat. Dietary cholesterol intake was 229 mg for wives 19-24 and 243 mg for older wives and, based on approximately 1,900 kcal, dietary cholesterol exceeded 100 mg/1,000 kcal in both age groups. Sodium intake averaged 3.2 g. Forty-five percent of the military wives did not meet two-thirds of the RDA for vitamins D, E, B-6, iron, folic acid, zinc, and magnesium. Less than 20% met two-thirds of the RDA for riboflavin, vitamin A, thiamin, iodine, selenium, and calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502395 TI - Fort Polk Heart Smart Program. Part IV: Lifestyles of military personnel and their families. AB - Lifestyles are major determinants in development of heart disease. Tobacco and alcohol use, physical activity, and hostility, a component of type A, were assessed in a sample of active military men and their wives at Fort Polk, Louisiana. Findings included: (1) a greater frequency of cigarette smoking at Fort Polk compared to national surveys; (2) a higher frequency of alcohol consumption in ages 30-39, and more blacks reported alcohol use than other race groups; (3) a greater frequency of alcohol use at Fort Polk compared to a worldwide military survey; (4) no consistent differences in lipid or blood pressure levels for high and low activity groups of wives; and (5) wives' hostility scores were low, and were not correlated with other cardiovascular risk factors. The implication of lifestyle descriptions is the need for intervention and health promotion, not only for military personnel, but also for their families. The significance of health promotion programs is the eventual reduction of health care costs and the well-being of families and fitness of military personnel. PMID- 8502397 TI - Utilizing field medical equipment to support fixed facilities during major renovation projects. AB - When a fixed facility plans for renovation, the ultimate goal is to provide continuous, cost-effective medical operations. One alternative is to utilize field medical equipment. The Deployable Medical Systems (DEPMEDS), even though designed for battlefield medicine, has been successfully used for six fixed facility renovation projects. As a direct result of various studies, several improvements have been implemented and recommended for the DEPMEDS equipment when used to support fixed facilities. These projects have provided a rich learning experience and have significantly improved the readiness posture of the AMEDD. PMID- 8502396 TI - Serum lipids and lipoprotein profiles of military personnel and their families: Fort Polk Heart Smart Program. AB - Serum lipid and lipoprotein distributions and their correlates were examined in white, black, and Hispanic Army personnel and their families (N = 589) as part of the Fort Polk Heart Smart Program. In general, blacks tended to have higher HDL-C and lower triglycerides and VLDL-C than whites and Hispanics, whereas Hispanics tended to manifest higher triglycerides, VLDL-C, and LDL-C than whites. Unlike black and Hispanic men, white men tended to have lower HDL-C than white women. In contrast to white men, both black and Hispanic men displayed elevated LDL-C compared with black and Hispanic women. A considerable proportion of individuals tended to manifest adverse lipoprotein patterns according to National Cholesterol Education Program guidelines for children and adults. Cigarette smoking and alcohol use were the major contributors to the variance of lipoproteins in men, whereas overweight and oral contraceptive use remained the major factors in this regard for women. These results indicate that early targeting of military personnel and their family members for primary prevention is highly desirable. PMID- 8502398 TI - Combat stress control in the post-war theater: mental health consultation during the redeployment phase of Operation Desert Storm. AB - The redeployment phase of Operation Desert Storm resulted in a number of clinical and casualty management challenges to the mental health support system. Psychological factors affecting post-combat adjustment may be unique to this short, successful operation. Evacuation policy and available assets will be discussed in light of their effects on clinical presentations, and recommendations made for combat psychiatric policy in future foreign interventions. PMID- 8502399 TI - Air Force mental health consultation: a six-year retention follow-up. AB - Follow-up data were collected 68 months after Air Force basic trainees were screened at a mental hygiene clinic. Trainees were given the Millon Clinical Multiaxial Inventory (MCMI) inventory and a clinical interview-recommended disposition. This process resulted in recommendations of immediate discharge for 65 trainees, administrative separation for 52, and return to duty for 48. None of the immediate discharge group served 4 years or more, only 5 of the administrative separation group did so, and 18 of the return to duty group did so. The passive-aggressive, anxiety, and dysthymia scales from the MCMI best differentiated between early discharges and those completing enlistments. Clinical judgment was of limited value in the recommendation of continued service and the trainees' simple referral for consultation was most powerful. PMID- 8502400 TI - The relationship between battle intensity and disease rates among Marine Corps infantry units. AB - Disease and non-battle injury (DNBI) rates were examined in conjunction with casualty rates across two Marine Corps operational scenarios, the assault on Okinawa and the Korean War. DNBI rates increased significantly with battle intensity among Marine infantry battalions involved in both operations. Highly significant positive correlations (p < 0.001) were evidenced between DNBI rate and wounded-in-action (WIA) rate, DNBI rate and killed-in-action rate, and DNBI rate and the preceding week's WIA rate among infantry units in both Okinawa and Korea. The severity of wounds and DNBI rate were also significantly correlated. PMID- 8502402 TI - A retrospective review of orthopedic patients returning from Operations Desert Shield and Desert Storm to an Army Medical Center. AB - A retrospective review of all casualties received related to Operations Desert Shield and Desert Storm was conducted at Madigan Army Medical Center. Of the 180 patients determined to have returned from the Persian Gulf theater of operations, 93 (52%) had at least one orthopedic diagnosis and 84 (45%) were transported with a primary orthopedic diagnosis. The evacuation diagnosis was not substantiated by medical center evaluation in 37 (40%), and 42 (45%) were returned to duty without further treatment. Thirty-five patients (38%) were evacuated for a condition for which they had previously been profiled at least once. Peacetime duty limitations must be accurate and appropriate with respect to potential wartime demands. PMID- 8502401 TI - A prototype multidisciplinary cancer screening clinic for the military medical facility. AB - Optimal treatment of cancer depends upon early diagnosis. With an aging retiree and dependent population, cancer diagnosis and management must be addressed by military medical treatment facilities (MTFs) in a coherent and cost-effective fashion. A prototype multidisciplinary cancer screening clinic is described which interdigitated MTF and local American Cancer Society resources. Sites screened included breast, prostate, skin, cervix, and oral cavity, with mammograms, prostate-specific antigens, PAP smears, and physical exams, as appropriate. Of 194 patient contacts over a 4-hour period, eight cancers were found and subsequently treated (five skin, three prostate). Patient selection criteria, screening results by site, lessons learned, and recommendations for future clinics are discussed. The multidisciplinary screening clinic is readily applicable to the MTF setting, cost-effective, and provides an invaluable service to eligible patients. PMID- 8502403 TI - Dysbaric osteonecrosis of the femoral diametaphysis. AB - A 28-year-old submarine officer was involved in a dysbaric exposure at 155 feet for 21 hours. Subsequent to rescue, he developed a painful osteonecrosis involving over two-thirds of the femoral shaft and distal metaphysis. Pain is totally atypical for a bony injury of this distribution but because of failure to improve after 12 months, he underwent a series of three operations: (1) core biopsy, (2) intramedullary reaming and intramedullary rod fixation of the femur, and (3) bone grafting to a metaphyseal defect in the distal femur. Serial MRI scans were used to follow the progression of his osteonecrosis. This case report documents the first reported dysbaric diaphyseal osteonecrosis requiring surgery and intramedullary fixation to obtain a satisfactory clinical result. PMID- 8502405 TI - Ties that bind. PMID- 8502404 TI - Bilateral breast masses in a man. AB - Other than gynecomastia, bilateral breast masses in a male patient is an unusual occurrence. We present a case of fat necrosis presenting in a male veteran as bilateral palpable breast masses. PMID- 8502407 TI - HHS division of nursing drafts strategy for 1993. PMID- 8502406 TI - Use the language of caring. PMID- 8502408 TI - The concerns of beginning nursing students. PMID- 8502409 TI - A BSN program for the U.S. Army Reserve. PMID- 8502410 TI - Preparation for advanced nursing practice. PMID- 8502411 TI - Teaching gerontological nursing in southern states. PMID- 8502412 TI - The many labors of the International Council of Nurses. PMID- 8502413 TI - Associate degree nursing programs accredited by the NLN 1993-94. PMID- 8502414 TI - Population-based care systems range from managed care to nursing centers. PMID- 8502415 TI - The shift of focus from provider processes to population outcomes. Consumer oriented and population-based care systems. PMID- 8502416 TI - Perspectives on outcome-oriented care systems. PMID- 8502417 TI - Research related to case management. PMID- 8502418 TI - Cautionary notes on innovation in nursing practice. PMID- 8502419 TI - Control or negotiation: a health care challenge. PMID- 8502421 TI - Case management in a small rural hospital. PMID- 8502420 TI - Case management in a retirement community. PMID- 8502422 TI - Population-based managed care: one hospital's experience. PMID- 8502423 TI - Managed care at the Johns Hopkins Hospital. PMID- 8502424 TI - The price of choice: managed care in America. PMID- 8502425 TI - Networks and databases: building blocks for the population-based care system. PMID- 8502426 TI - The clinical practice of supplemental nursing personnel. PMID- 8502427 TI - The ferritin genes: their response to iron status. AB - Iron is a required nutrient which, at high concentrations, can peroxidize cell lipids and other cellular components. To prevent excess iron from damaging cells, it is stored in ferritin, which consists of a shell of protein subunits of two related types, H (heavy) and L (light), surrounding a cavity in which the iron can be deposited. In order to prepare for a rapid increase in ferritin in response to a rise in cellular iron, a large number of dormant ferritin mRNAs are accumulated in the cytoplasm. These can be rapidly activated to yield a large population of ferritin subunits. Regulation is achieved through a 28-nucleotide "stem-and-loop" structure near the beginning of the H- and L-ferritin mRNAs. When this structure is associated with a binding protein (iron regulatory element binding protein, IRE-BP), translation of the ferritin mRNA cannot proceed. However, when intracellular iron accumulates, IRE-BP releases its hold and translation of the mRNA then takes place. IRE-BP has been identified as a cytosolic form of aconitase, containing several fourfold iron-sulfur clusters. Within each cluster one iron atom is labile; this may be the mechanism by which IRE-BP responds to intracellular iron levels. Finally, transcription of the L- and H-genes shows that L is preferentially transcribed in response to increased iron intake, whereas H responds to cell differentiation and other factors. More work is needed to define independent transcription of the individual genes, including regulation of components other than the 28-nucleotide segment. PMID- 8502428 TI - Malnutrition in Iraqi children following the Gulf War: results of a national survey. AB - The community-based Iraq Infant and Child Mortality and Nutrition Survey was designed to estimate mortality and nutritional status of Iraqi infants and children under five years of age after the Gulf conflict of 1991. This article presents results from a nationwide nutritional survey conducted between August 25 and September 5, 1991. A random multistage cluster sample was selected, including a subsample of 2676 children in the anthropometric analysis. The percentage below -2 standard deviations was 21.8% for height-for-age, 11.9% for weight-for-age, and 3.4% for weight-for-height. It is possible that the observed prevalence of wasting was an underestimate, resulting from a survivor bias. This observation suggests that cross-sectional nutritional surveys may not be the most appropriate method for assessing the effect of the Gulf conflict on the nutritional status of children in Iraq. Longitudinal information on child mortality and nutritional status would be more useful in predicting the likelihood of famine. PMID- 8502429 TI - Cow's milk, diabetes, and infant feeding. AB - Recently, a link between the serum level of antibody to cow's milk protein and the onset of insulin-dependent diabetes mellitus in humans was reported. This observation renewed controversy regarding the suitability of cow's milk in infant diets. PMID- 8502431 TI - Do diets high in iron impair manganese status? AB - A recent study investigated the effect of dietary heme- and nonheme iron intake on iron and manganese status in young women. Despite representing only 5% of total dietary iron intake, heme iron was the primary determinant of iron status but had no influence on manganese status. In contrast, diets high in nonheme iron were not associated with better hematologic status, but serum manganese values were lower. PMID- 8502430 TI - Antioxidant nutrition and cataract in women: a prospective study. PMID- 8502432 TI - Low-copper diets increase aortic lipid peroxides in rats. AB - Dietary factors other than fat and cholesterol may contribute to the pathogenesis of cardiovascular disease. One hypothesis states that low dietary copper contributes to risk. In a recent study, rats fed diets marginal or deficient in copper had reduced aortic copper-dependent superoxide dismutase activity, increased generation of aortic lipid peroxides, and reduced aortic prostaglandin production. These vascular changes may contribute to atherogenesis. PMID- 8502433 TI - Plant now; reap later. PMID- 8502434 TI - From a plethora of paradigms to parsimony in worldviews. PMID- 8502435 TI - What constitutes nursing research? PMID- 8502436 TI - The same-thing-yet-different phenomenon: a way of coming to know--or not? PMID- 8502437 TI - Psychological determinism and the evolving nursing paradigm. AB - The purpose of this article is to explore three behaviorist theories and their roles within the evolving paradigm of nursing. The authors suggest that the behaviorist theories of locus of control, self-efficacy, and the health belief model are derived from deterministic philosophical premises. These premises are in direct conflict with the premise of free will. As interpreted by the authors and many others, the emerging paradigm of nursing relies on the free will of the individual, the ability of the individual to choose for himself/herself what course of action to take, to avoid, or to pursue. The authors address the psychological deterministic philosophical premises within the three theories and utilize nursing theories to compare and contrast the views of free will and determinism. Finally, they suggest that the use of borrowed and applied theories should decline when nurse scientists are true to the philosophical assumptions of theories within nursing science. PMID- 8502438 TI - Therapeutic touch and postoperative pain: a Rogerian research study. AB - This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested. PMID- 8502439 TI - Dynamism in practice: parenting within King's framework. AB - A dynamic approach to parenting in a neonatal intensive care unit provides a framework to test King's nursing theory. The framework is based on selected concepts from King's theory of goal attainment and current literature on parenting. The framework stresses the valuational components of human interaction. This article describes an attempt to move neonatal care from medicalization of parenting toward transaction between parents and nurses. PMID- 8502441 TI - Adapting the Neuman systems model for family nursing. AB - Family nursing is in the early stages of development, and there is often difficulty in translating nursing conceptual frameworks into terms that are less abstract and more readily usable in the family practice arena. Yet the conversion of abstract ideas to concrete descriptions is necessary if nursing theory-based practice is to expand. This article describes the client system known as family within the Neuman systems model. Based on clinical data and the experience of nurses using the Neuman model in practice, a description of the family as client is developed. The five variables of Neuman's model are identified and the terms used in describing the family system are clarified. A rationale for the application is also presented. PMID- 8502440 TI - Adaptation to chronic illness: a program of research for testing nursing theory. AB - The adaptation to chronic illness framework, an elaboration of the Roy adaptation model for chronic illness, provided direction for a program of nursing research. The purposes of investigations within the program were (a) to identify predictors of adaptation to chronic illnesses and (b) to determine whether the relationships between the variables differed by diagnostic group. A total of 597 adults, representing various chronic illness groups, participated in longitudinal studies during a seven-year period. Health-related hardiness and engagement in health promotion activities consistently predicted both physiological and psychosocial adaptation in all chronic illness groups. In addition, the individual's perception of the degree of disability caused by the illness was related to psychosocial functioning. Comparison of adaptive responses between the groups revealed significant differences in physiological adaptation but no significant differences in psychosocial adaptation. Results clarify relationships posited using the theoretical framework and support the value of using nursing models to guide nursing research. PMID- 8502442 TI - The caring moment and the green-thumb phenomenon among Swedish nurses. AB - People who have a special gift for gardening are sometimes described as having a green thumb. Likewise, some nurses have a green thumb for nursing. The aims of this study were to identify and describe the characteristics of green-thumb nurses and of caring situations. A descriptive-exploratory design was used, and 16 nurses, recruited by their superiors, participated in semi-structured interviews. The findings revealed that the green-thumb nurse is competent, compassionate, and courageous. The essence of the caring moment was identified as the green-thumb nurse's ability to act on the spur of the moment, using her competence, compassion, and courage. PMID- 8502443 TI - Reversal of female sterilisation: outcome of 210 referrals. AB - AIMS: To determine the outcome of request for reversal of sterilisation and to compare demographic and social factors of women who subsequently withdrew their request with those who proceeded with the reversal assessment and operation. METHODS: Information relating to the sterilisation and regret intervals were sought from 210 women. Demographic and social factors were recorded and the outcome of the reversal request determined. Patients who withdrew or were deferred/declined were compared on relevant factors with the group who proceeded to, or are still planning, the reversal operation. RESULTS: Ninety-two (44%) withdrew before or during the assessment phase. Another 13 withdrew after laparoscopy identified a poor prognosis. Three declared their intention not to conceive after they underwent the reversal operation. To date, 83 have had surgery with the cumulative intrauterine pregnancy rate at 1, 2 and 3 years being 0.46, 0.62 and 0.78 respectively. In comparing those women who proceeded and withdrew, there were no differences in mean age at referral, age at sterilisation, the number of living children nor marital status. The regret interval prior to referral was significantly longer in the women who proceeded (27.9 and 19.5 months respectively, p = 0.03). Those who were highly motivated in their reversal request were also more likely to proceed (p = 0.003). CONCLUSIONS: There is a large dropout rate of women who seek a reversal of sterilisation. Women who regret sterilisation may have sought sterilisation as a solution to problems that were psychosocial rather than contraceptive in nature. We stress the importance of counselling for both sterilisation and its reversal, since in the latter many developmental personality and relationship problems remain unresolved. PMID- 8502444 TI - Women and coronary heart disease. PMID- 8502446 TI - An instance of tungiasis in New Zealand. PMID- 8502445 TI - Importance of diabetic foot admissions at Middlemore Hospital. AB - AIMS: To investigate the costs and mortality associated with admission for diabetic foot problems. METHODS: Identification of patients by codes for diabetes and peripheral vascular disease from routinely collected hospital discharge data. Information was collected retrospectively from charts. Post discharge outcome was assessed by discussion with general practitioners. RESULTS: 357 patients accounted for 503 admissions. 11-15% of patients (n = 49) were admitted for diabetic foot problems. Patients with type 1 diabetes had shorter lengths of stay than those with type 2 diabetes, were more likely to be admitted with chronic renal failure and less likely to be admitted with ischaemic heart disease. Maori and Pacific Island patients with type 2 diabetes were admitted at a younger age than Europeans (53 (SD12) vs 56 (11) vs 69 (13) years respectively, p < 0.001). Admissions for diabetic foot problems resulted in the longest hospital stay in comparison with other causes (19 (1-184) days vs 8 (1-116)) days. Average cost per diabetic foot admission was $12,500 with a total annual cost of over $600,000. CONCLUSION: The diabetic foot is expensive and yet these costs are largely avoidable with improvement in patient education, motivation, monitoring and earlier intervention. It would be better to have in place improved community and hospital care before the predicted growth in the diabetic population associated with ageing. PMID- 8502447 TI - General practitioner fundholding: experimental sideshow or main event of the NHS reforms? PMID- 8502448 TI - Child mortality in New Zealand. PMID- 8502449 TI - Complications of legal abortion. PMID- 8502450 TI - Computerised age/sex registers. PMID- 8502451 TI - Carbon monoxide as cardiotoxin. PMID- 8502452 TI - Occupational overuse syndrome. PMID- 8502453 TI - The Charles F. Prentice Medal Award Lecture 1992: optometry and the preservation of visual health. AB - The discovery that sunlight is the primary causal factor in a family of serious eye diseases is doubly significant because it offers a simple, safe, and inexpensive means of preventing all of them simultaneously. The need for prevention is underscored by the terrible expense of sunlight-related eye diseases--$50 billion for cataract surgery in the U.S. during the past decade, plus the added cost to society of visual impairment and blindness. There is widespread scientific agreement that the use of eyewear with lenses that preferentially absorb the high-energy components of the solar spectrum, including 100% of UV radiation, will substantially reduce the risk of all sunlight-related eye diseases without interfering with visual function. A program to preserve visual health by such means can be based primarily on public education. Because the method of preventing these diseases is the use of appropriate eyewear, this unprecedented opportunity falls within the field of expertise of optometry. PMID- 8502455 TI - Impact of new and emerging instrumentation in optometry. AB - Traditional tests of vision emphasize visual acuity, visual fields, and testing for hereditary color vision defects. New instrumentation for testing vision has proliferated due to advances in our knowledge of the visual system, the availability of new technologies, the introduction of computers into practice, and the expanded scope of optometric practice. Each is discussed in relation to the subsequent symposium papers by other authors. PMID- 8502454 TI - The Glenn A. Fry Award Lecture 1992: aqueous humor proteins: a key for unlocking glaucoma? AB - In this report I summarize recently reported studies which establish the existence of a previously undocumented diffusional pathway for plasma-derived proteins from the ciliary body stroma to the anterior chamber of the normal mammalian eye via the iris root. The data support the hypothesis that nearly all of the plasma-derived protein present in the aqueous humor of the anterior chamber arrives via this pathway, thus by-passing the posterior chamber. Additional studies suggest that some of the protein transported via the pathway is shunted directly into the trabecular meshwork and aqueous outflow pathways. Perfusion studies show how the perfused eyes were later immunohistochemically stained to reveal the distribution and qualitative amounts of serum albumin. These studies strongly suggest that the well-known "wash-out" effect, encountered in experimental studies of aqueous outflow, arises predominantly from wash-out of the protein depot that serves as the anterior diffusional pathway for proteins. Taken as a whole, these studies support the hypothesis that protein is a physiologically relevant and important element in the generation of normal aqueous outflow resistance, possibly more important than glycosaminoglycans (GAG's). PMID- 8502456 TI - New methods for discriminating neural and optical losses of vision. AB - Visual acuity, the premier test of visual function, is analyzed as a three-stage, hierarchical sequence beginning with the detection of spatial contrast, followed by the resolution of that contrast into spatially separate elements, and ending with the identification of a particular arrangement of elements as one of several possible test objects, e.g., a letter in the Snellen alphabet. Each stage in this process has its own inherent limitations which are associated with different stages of the visual pathway. New methods are described for testing each stage of the hierarchy individually for the purpose of identifying the weak link in the chain, thus paving the way for differential diagnosis of optical and neural losses of vision. PMID- 8502457 TI - Role of automation in new instrumentation. AB - In recent years there has been an unprecedented increase in the development of automated instrumentation for ophthalmic diagnostic and assessment purposes. An important part of this growth in automated clinical ophthalmic instrumentation has been directed to perimetry and visual field testing. In less than 15 years automated perimetry has advanced from a laboratory curiosity to become the standard for clinical visual field testing. This paper will provide a brief overview of the impact that automated perimetry has had on current clinical ophthalmic practice and patient management. It is presented as a general example of the influence that automated instrumentation has exerted on the clinical environment. PMID- 8502458 TI - New procedures for detecting early vision losses in the elderly. AB - With the proportion of elderly in the population increasing, and with improving methods for modifying or treating age-related changes affecting the visual system, there is an increasing need for broader and more specific assessments of vision functions in the older patient. As age increases, vision function changes are diverse. Here we discuss methods for the clinical assessment of three of these functions; namely, visual acuity, contrast sensitivity, and disability glare. Visual acuity remains the most useful test of visual function and improved chart designs and scoring methods enhance our ability to detect and monitor change. A variety of different approaches to assessing contrast sensitivity and contrast sensitivity testing should facilitate the diagnostic process and help to predict and explain changes in visual functioning. Disability glare can be expected to become more important in the routine evaluation of the ocular media and for this several new tests have recently become available. PMID- 8502459 TI - New procedures for evaluating vision functions of special populations. AB - Research over the last few decades has demonstrated the rapid development of vision function that occurs in infancy with near-adult levels reached before the age of 1 year. This period of rapid development coincides with the period of maximum sensitivity to insult. These facts emphasize the importance of effective screening techniques for visual disorders. Off-axis photorefraction is described as a new and effective screening technique for detection of refractive errors, media opacities, and strabismus. Separate from screening, a significant need exists for optometric vision evaluations in special populations. Normal infants, developmentally delayed or multi-handicapped children and adults, and cognitively impaired adults are examples of special populations who are difficult to examine with standard optometric techniques. New procedures for measuring visual acuity, contrast sensitivity, color vision, and stereopsis using behavioral or electrophysiological measures are described. Advantages and disadvantages of the different techniques are discussed. PMID- 8502460 TI - Acceptance of different multifocal contact lenses depending on the binocular findings. AB - In a clinical study the subjective acceptance as well as the quality of different visual functions was examined during the wearing of three multifocal lenses (Ciba Spectrum Bifocal, Allergan Echelon, and Essilor Variations). Ten subjects wore each of the 3 contact lens types for a period of 12 to 21 days after the binocular finding (bicentral or disparate vision within the Panum's area); further functions such as contrast or scotopic vision were qualified and/or quantified in a basic examination. All subjects (N = 5) with the binocular finding orthophoria/motorcompensated heterophoria preferred the Ciba Spectrum Bifocal. Furthermore, all visual functions of the 10 test persons were clearly reduced with all 3 multifocal contact lenses. A correlation between the "preferred contact lens and the detailed subjective acceptance" and/or the "subjective acceptance and the functional measurements" could not be proven as statistically significant. PMID- 8502461 TI - Accommodative hysteresis of refractive errors in light and dark fields. AB - We investigated the accommodative hysteresis of the refractive error in the light and also in the dark in 19 healthy young women. We measured refractive error under light and dark conditions using the Nidek Autorefractometer AR 1600 with its target light on or off. Then we measured refractive error in the light and in the dark again after they performed nearwork. Post-task refractive error was measured after reading a magazine for 15 min wearing glasses -3.0 D over their distance correction. Nearwork produced a myopic shift of 0.21 D in the refractive error in the light but no shift in the refractive error in the dark. Refractive error in the dark increased significantly by the near task in eyes with more than 2.0 D of myopia, but it did not increase in eyes with less than 2.0 D of myopia. These apparent differences in the accommodative hysteresis are due to the different pre-task baseline values. If the post-task refractive error is evaluated with the same pre-task baseline value, the accommodative hysteresis does not differ among different refractive errors whether measured in the light or in the dark. PMID- 8502462 TI - Relation between the dark focus of accommodation and refractive error--a cycloplegic study. AB - We measured distance refractive error (Dist R), dark refractive error (Dark R), and cycloplegic refractive error (Cyclo R) in 196 subjects whose ages ranged from 4 to 17 years, using the Canon Autoref R-1. We defined the values of (Dark R- Dist R) as DFcus (Dist R) and those of (Dark R--Cyclo R) as DFcus (Cyclo R) in this study. Although DFcus (Dist R) was larger in less myopic and more hyperopic eyes similar to DFcus (Cyclo R), it was zero or plus in high hyperopic eyes, unlike DFcus (Cyclo R). We found Dist R was more strongly influenced by Cyclo R than was Dark R. It is not adequate to use Dist R as the far point for precise evaluation of the dark focus. We should use the difference between Dark R vs. Cyclo R as the true value of the dark focus of accommodation. PMID- 8502463 TI - Testing the FOCOMETER--A new refractometer. AB - The FOCOMETER, an optometer which measures spherical refractive errors, is intended to provide rural or economically disadvantaged populations spherical prescriptions without the need for complicated protocols, expensive equipment, or electricity. FOCOMETER readings were compared with the spherical equivalent determined from autorefraction and subjective trial lens refractions in children, and with retinoscopy in adults. Over the range of refractive errors tested (-4 to +5 D) reasonably close readings, within one-half a diopter, were found for comparisons with autorefraction and retinoscopy and about one-tenth of a diopter difference was found between subjective refractions and the FOCOMETER. PMID- 8502464 TI - [The weight-bath and its biomechanics]. AB - Authors report about build-up, the biomechanics, the indication, the contraindication and the method of appliance of traction bath. They were the first who made biomechanical calculations so that they could assess the extension power on the different parts of the spinal column as well as on the big joints of the lower limbs during traction bath treatment. The extension power in the traction bath depends on the way of the suspension, the weight of the human body in water, its relative density and the place and size of the weights. Supported by calculations extension power was defined in the suspension point and at any distance from it in unloaded conditions and in loading with various weights. The extension power of the net weight of the body was 2-4 kgs in the suspension point and at the neck (cervical vertebrae) while on the lumbar vertebrae it was the half of that value. The change in the power on the vertebrae (spinal column) was plotted against the body weight, the relative density and the applied weights. PMID- 8502465 TI - [Necrosis of the colon and rectum as a complication of aortic reconstruction surgery]. AB - The author reports on two patients operated on for necrosis of left colon after aorta-bifemoral by-pass reconstruction and presents another by whom ischemic rectum necrosis occurred as complication of aorta aneurysm. The paper deals with the symptomatology, diagnostics, anatomic and surgical technical causes of the serious complication. Results may be improved by early recognition of complication and the consequent performance of examinations related to it. PMID- 8502466 TI - [Smoking and mortality: longitudinal epidemiologic study (1975-1991)]. AB - The authors have started a basic screening examination in one of the industrial districts of Budapest in 1975. The district has nearly 100,000 inhabitants. The aim of the examination was to determine the risk factors of lung cancer. 30,566 persons have participated. The health of all patients has been followed up between 1975-1991. During this period 3,573 patients have moved out of the district. On 26,993 patients they have examined the death ratio, the prospective life-span, in the various age groups divided into subgroups according to their smoking habits. They have studied the formation of death rate in the four risk groups determined by them on the basis of the simultaneous examination of more lung cancer risk-factors (risk-free, moderate, high and superhigh risk groups). During these 16 years the death rate both among the heavy smokers and among patients in the high and superhigh risk groups has been two, three, even almost five times higher than that in the non-smoking and in the risk-free group of the relatively younger age groups of the population (born between 1921-1930 and 1931 1938). The knowledge of these connections makes economic calculations possible in respect of life and health insurance. PMID- 8502467 TI - [The value of transesophageal echocardiography in the detection of left coronary proximal stenosis]. AB - Transesophageal echocardiography was performed in 34 patients before coronary angiography for suspected coronary artery disease to determine the usefulness in the detection of proximal left coronary stenosis. The control group consisted of 18 patients in whom coronaroangiography seemed to be negative. The diameter of the visualized coronary arteries, the systolic and diastolic peak flow velocities were measured. The left main coronary artery was visualized in 32 patients, the left anterior descending artery in 31 and the proximal part of the circumflexus artery in 23 patients of the coronary artery disease group, and in the same rate in the control group. The visualization of the right coronary artery was available only in 20-25% because of technical difficulties. The diastolic peak flow velocity over 60 cm/s in the left anterior descending artery reflected proximal stenosis with high sensitivity. In four patients transesophageal echocardiography was performed before angioplasty and after successful intervention. The high diastolic peak flow velocity significantly decreased in every patient. According to the observations the method can be used to perform morphologic and functional measurements on the left proximal coronary arteries. PMID- 8502469 TI - [Management of the diabetic foot (with special reference to diabetic gangrene)]. PMID- 8502468 TI - [Rare congenital forms of bone marrow deficiency]. AB - Cases of rare congenital forms of aplastic anaemia are presented. Fanconi anaemia is most frequently diagnosed, while reticular dysgenesis, amegakaryocytic thrombocytopenia and dyskeratosis congenita occur exceptionally rarely. A presumably new entity of congenital aplastic anaemia called "RAC" syndrome (retinopathy--aplastic anaemia--central nervous system abnormalities) is presented too. A short summary of the pathomechanism of congenital aplastic anaemias and present therapeutic attempts, including the possible therapeutic use of the newly discovered stem cell factor are described. PMID- 8502470 TI - The consistent 13q14 translocation breakpoint seen in chronic B-cell leukaemia (BCLL) involves deletion of the D13S25 locus which lies distal to the retinoblastoma predisposition gene. AB - Structural rearrangements involving chromosome 13 are frequently seen in B-cell chronic lymphocytic leukaemia. The presence of reciprocal translocations involving 13q14 in 10-15% of cases pinpoints the location of a gene important in leukaemogenesis. In order to characterise the exact location of the 13q14 breakpoint, somatic cell hybrids were constructed between mouse 3T3 cells and leukaemic cells from 5 patients with translocations involving chromosome 13. Hybrid pairs were isolated which carried either of the two derivative chromosomes carrying subsections of 13 and the position of the breakpoint investigated using a series of probes along the length of the chromosome. In all cases breakpoint region associated with rhabdomyosarcoma tumours and proximal to the D13S31 locus which lies in 13q14.3. In three translocations the RB1 gene was deleted as a result of the translocation but in at least one other case the BCLL breakpoint did not involve the RB1 gene, which consistently cosegregated in hybrids carrying other proximal markers. The D13S25 probe, which lies between RB1 and D13S31, however, was deleted in the translocation retaining RB1. It appears therefore that deletion of a gene(s) in this 2Mbp region is a critical event in some cases of BCLL tumorigenesis. PMID- 8502471 TI - p59fyn in rat brain is localized in developing axonal tracts and subpopulations of adult neurons and glia. AB - Expression of the c-fyn proto-oncogene was analysed in the developing and adult rat brain by subcellular fractionation and immunocytochemistry using polyclonal antibodies specific for its protein product (p59fyn). Immunoperoxidase staining revealed widespread localization of p59fyn in developing axonal tracts throughout the fetal (E18) rat brain. fyn immunoreactivity was not observed in most axon rich regions of the adult brain, but continued to be expressed at elevated levels in the adult olfactory and vomeronasal systems. At other sites in the adult rat brain, fyn immunoreactivity was restricted to cell bodies of neuronal subpopulations, especially those in brain stem and hypothalamic nuclei, and to subpopulations of glial cells along axonal tracts in the medulla, optic nerve and white matter of the spinal cord. In the peripheral nervous system, fyn staining was also prominent in Schwann cells. Subcellular fractionation of fetal and adult rat brain confirmed the immunocytochemical localization, demonstrating an enrichment of p59fyn in membranes from a fetal brain fraction containing nerve growth cones, and lower levels in adult brain where there was only a small enrichment in synaptosomal membranes. The developmental regulation of p59fyn suggests that the fyn tyrosine kinase may serve separate cellular roles in axonal growth and specialized functions of mature neurons and glia. PMID- 8502472 TI - Absence of a paused transcription complex from the c-myc P2 promoter of the translocation chromosome in Burkitt's lymphoma cells: implication for the c-myc P1/P2 promoter shift. AB - We have shown recently that pausing of RNA polymerase II (pol II) at the transcription start site regulates expression from the P2 promoter of the proto oncogene c-myc. RNAs initiated at the P2 promoter usually contribute > 80% to steady-state c-myc RNA levels in normal cells. In Burkitt's lymphoma (BL) cells c myc is chromosomally translocated to an immunoglobulin (Ig) gene and preferentially transcribed from the upstream P1 promoter. We have studied the activity of c-myc promoters in two BL cell lines with high expression of P1 RNA. Kinetic nuclear run-on experiments show that the initiation rate at the c-myc P1 promoter in BL2 and BL60 cells is not increased compared with control BJAB cells, whereas the number of paused polymerases at the P2 promoter is greatly diminished. The translocation c-myc gene of BL60 cells was cloned and stably transfected into the BL cell line Raji. The transfected c-myc gene regained the ability to form a paused transcription complex at the c-myc P2 promoter. The data suggest that a paused polymerase at the c-myc P2 promoter impedes transcription from the upstream P1 promoter on a normal c-myc gene. The c-myc gene on the translocation chromosome in BL cells has lost the ability to retain pol II at the P2 promoter, probably by interaction with elements of the adjacent Ig gene locus. PMID- 8502473 TI - ADP-ribosylation of the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle. AB - Using botulinum C3 exoenzyme, which specifically ADP-ribosylates the rho gene products (rho proteins), we examined the role of these proteins in cell cycle progression in Swiss 3T3 cells. Incubation of cell lysates with C3 exoenzyme revealed a single [32P]ADP-ribosylated protein with an M(r) of 23K. This protein was identified as rhoA protein by isoelectric focusing and peptide mapping. When C3 exoenzyme was added to the culture, it ADP-ribosylated the substrate protein in the cells and reduced their growth rate and saturation density. The reduction was dependent on the amount of C3 exoenzyme and on the extent of ADP-ribosylation of the rho protein in the cells. Flow cytometric analysis of logarithmically growing cells showed that the enzyme treatment concentration-dependently accumulated the cells in the G1 phase of the cell cycle. When G1-enriched cells were treated with C3 exoenzyme and cell cycle progression initiated by the addition of serum was monitored, inhibition of G1-S transition was clearly observed. These results suggest that the rhoA gene product plays a critical role in G1-S progression in cultured Swiss 3T3 cells and that the ADP-ribosylation abolishes this activity and causes the cells to accumulate in G1 phase. PMID- 8502474 TI - Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. AB - The various steps of differentiation and maturation in spermatogenesis are well characterized and offer a convenient system to explore the possibility that p53 plays a role in cell differentiation in vivo. In situ hybridization experiments indicate that the p53 gene is expressed in tetraploid primary spermatocytes at the meiotic pachytene stage of the first round of spermatogenesis in young mice. An analysis of spermatogenic cells treated with anti-p53 antibodies reveals that the p53 protein is expressed in a discrete tetraploid cell population, with size and cellular structure parameters characteristic of midpachytene spermatocytes. The specific kinetics of p53 expression in the first round of spermatogenesis and its localization in adult testicular sections, coupled with the fact that the protein is expressed in the largest cells with lower DNA density, suggest that p53 expression is confined to the tetraploid primary spermatocytes of the meiotic pachytene phase. These observations identify p53 protein as a potential member of the meiosis control protein family. PMID- 8502476 TI - Quantification of p53 protein in tumor cell lines, breast tissue extracts and serum with time-resolved immunofluorometry. AB - We have developed a highly sensitive time-resolved immunofluorometric procedure for quantifying mutant or wild-type, human or murine, p53 protein. The method uses monoclonal PAb240 or PAb421 antibodies for capture and a polyclonal rabbit antibody for detection. The final immunocomplex is quantified with an alkaline phosphatase substrate which, when hydrolyzed by the enzyme, forms highly fluorescent long-lived complexes with Tb(3+)-EDTA. The detection limit is approximately 1 pg of protein per assay. The assay was applied for the quantification of p53 protein in lysates from 23 cell lines and overproducers of mutant protein were identified. Eight hundred cancer patients sera tested negative for the presence of p53. We have also applied the quantitative immunofluorometric procedure for measuring mutant p53 protein in breast tumor extracts specifically prepared for steroid hormone receptor analysis. Sixty-four out of the 264 extracts (24%) were positive for p53. Significant negative correlations between levels of p53 and steroid hormone receptors were found. The proposed analytical methodology simplifies the assessment of p53 status in tumor extracts, has many advantages over immunohistochemical techniques and is proposed as a method of choice for routine clinical use and other investigations involving p53. PMID- 8502475 TI - Wild-type p53 induces apoptosis in a Burkitt lymphoma (BL) line that carries mutant p53. AB - All Burkitt lymphoma (BL) biopsies and cell lines carry a c-myc/Ig translocation. The resulting constitutive activation of c-myc is regarded as an essential factor for the progressive growth of the tumor cells. At least 60% of BL cell lines carry a mutated p53 gene as well. It has been shown that the growth of mutant p53 carrying tumor cells could be inhibited by the introduction of wild-type p53. In order to examine whether this also applies to the presumably 'myc-driven' BL cell, we have transfected the Epstein-Barr virus (EBV) negative BL41 cell line with a temperature sensitive p53 mutant (p53-Val135) that expresses p53 with a largely mutant conformation at 37.5 degrees C and mostly wild-type conformation at 32 degrees C. At 37.5 degrees C, the p53-Val135 transfected cells behaved like the parental or neo transfected control cells. However, expression of exogenous wild-type p53 at 32 degrees C resulted in a rapid reduction of the number of viable cells while the parental and neo control cells remained unaffected. Cell death was due to apoptosis as shown by chromatin and nuclear condensation and specific DNA fragmentation. The first signs of apoptosis were evident after 10 h at 32 degrees C and after 3 days 90-100% of the cells had undergone apoptosis. These findings indicate an incompatibility between expression of wild-type p53 and progressive growth of BL cells if their neoplastic development has included a p53 mutation. The question whether apoptosis was induced in by the wild-type protein per se or by the contradictory signals of a constitutively activated c myc and wild-type p53 needs further investigation. PMID- 8502477 TI - Mutation of the serine 15 phosphorylation site of human p53 reduces the ability of p53 to inhibit cell cycle progression. AB - Overexpression of wild-type p53 prevents cells from entering the S phase of the cell cycle. The amino-terminal transactivation region of p53 is phosphorylated by several protein kinases, including DNA-PK, a nuclear serine/threonine protein kinase that in vitro requires DNA for activity. DNA-PK was recently shown to phosphorylate serines 15 and 37 of human p53 (Lees-Miller et al., 1992. Mol. Cell. Biol., 12, 5041-5049). To prevent phosphorylation at these sites, mutants were constructed that changed the codons for serine 15 or serine 37 to alanine codons. Expression of p53-Ala-37 in stably transformed T98G cells blocked progression of the cells into S phase as well as did the expression of wild-type p53. In contrast, p53-Ala-15 was partially defective in blocking cell cycle progression. Several cell clones transformed with the mutant p53-Ala-15 gene expressed normal levels of p53 mRNA but accumulated little or no detectable p53 protein. However, by using a transient expression system driven by a strong cytomegalovirus promoter, we showed that the inability of p53-Ala-15 to fully block cell cycle progression was not due to inadequate levels of expression or to a failure of the mutant protein to accumulate in the nucleus. These results suggest that phosphorylation of Ser-15 may affect p53 function. PMID- 8502478 TI - The core promoter region of the P-glycoprotein gene is sufficient to confer differential responsiveness to wild-type and mutant p53. AB - The overexpression of P-glycoprotein is thought to be responsible for resistance to chemotherapy in some non-responsive cancers. The mechanism by which P glycoprotein is overexpressed in human tumors is poorly understood. However, several lines of evidence suggest that the major regulatory mechanism of P glycoprotein overexpression in human tumors is at the transcriptional level. During tumor progression one of the most commonly observed alterations is mutation of the p53 tumor-suppressor gene. It has been shown that the p53 protein plays a role in transcriptional regulation. To gain insight into the effect p53 protein may have on P-glycoprotein promoter activity, we transiently co transfected plasmids containing the hamster pgp1 or human mdr1 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene with plasmids encoding either wild-type or mutant p53 protein into Chinese hamster ovary (CHO) cells. In this report, we show that wild-type p53 protein represses P-glycoprotein promoter activity, while mutant forms of p53 protein enhance P-glycoprotein promoter activity. Furthermore, we present data which indicate that the transcriptional regulatory effects of p53 are mediated through interactions with pgp1/mdr1 core promoter sequences. These findings have implications for our understanding of the molecular mechanism(s) by which p53 protein functions as a transcriptional regulator of gene expression. In addition, our results suggest a mechanism by which P-glycoprotein may be overexpressed in human cancers that also express mutant forms of p53 protein. PMID- 8502479 TI - Human ERG-2 protein is a phosphorylated DNA-binding protein--a distinct member of the ets family. AB - We describe the identification of the ERG-2 gene products using an antibody raised against recombinant human ERG-2 protein. ERG-2 is a nuclear phosphoprotein and binds to purine-rich sequences (C/G)(C/a)GG-AA(G/a)T. ERG-2 protein, with a half-life of 21 h, is considerably more stable than the short-lived ETS-1 or ETS 2 proteins. Its phosphorylation is stimulated by phorbol myristate acetate (PMA), but not by Ca2+ ionophore treatment. ETS-1 protein is phosphorylated by Ca(2+) dependent events, whereas ERG-2 protein is phosphorylated by activation of protein kinase C, suggesting their involvement in distinct signal transduction mechanisms. The expression of ERG-2 protein is restricted to few cell types and is high in early myeloid cells, indicating that it may function at an early stage of hematopoietic lineage determination. The DNA-binding sequence for ERG-2 protein is identified by using a random oligonucleotide selection procedure. The selected sequence is very similar to the binding sequence determined for human ETS-1 using the same method. Like other ets proteins, ERG-2 is a sequence specific DNA-binding protein and is expressed at higher levels in early myeloid cells than in mature lymphoid cells. These results suggest that it may act as a regulator of genes required for maintenance and/or differentiation of early hematopoietic cells. PMID- 8502480 TI - The hepatitis B virus (HBV) pX transactivates the c-fos promoter through multiple cis-acting elements. AB - The hepatitis B virus (HBV) X protein (pX) stimulates transcription regulated by cis-acting elements that control many viral and cellular genes, including the c myc and the c-fos proto-oncogenes. Using several c-fos promoter deletion mutants, we found the serum-responsive element (SRE) located at -315, the modified TPA responsive element located at -296 (fos-AP-1 binding site, FAP) and the region spanning from nucleotide -220 to -120, which contains an NF1-like site and several stretches of sequence homologous to the AP-2 consensus binding sites, to be responsive to pX. pX does not modify the pattern of the retarded complexes bound to the SRE/FAP region which, in our system, appears to be occupied by SRE binding factors. The activation of the SRE does not involve complex formation between SRE-binding factors and pX, it is not associated with an increase in serum response factor binding to the SRE and it does not determine changes in SRE mobility-shift pattern. PMID- 8502481 TI - Regulated expression of the retinoblastoma gene in differentiating embryonal carcinoma cells. AB - The expression of the retinoblastoma susceptibility (RB) gene was investigated in P19 embryonal carcinoma cells and in these cells induced to differentiate with retinoic acid (RA) or with dimethyl sulfoxide (DMSO). In undifferentiated cells very low levels of RB mRNA and protein were present. DMSO-treated P19 cell cultures develop into mesodermal and endodermal cells and RB expression increased only slightly in these differentiating cells. RA-treated P19 cells develop into neuroectoderm and this differentiation was accompanied by a marked increase in RB expression with mRNA levels increasing 15 fold by 4-6 days following initiation of RA treatment. No such increase occurred in mutant cells that fail to respond to RA. The RB promoter did not appear to be directly activated by RA. Nevertheless, the increase in RB expression in RA-treated cells appeared to be due to enhanced initiation of transcription because cells transfected with a reporter gene driven by the RB promoter expressed the reporter gene with kinetics similar to that of the RB gene. Thus the activation of the RB gene appears to be achieved indirectly by RA-induced factor(s) in differentiating neuroectodermal cells. The post-mitotic neurons that developed in RA-treated cultures contained only the hypophosphorylated form of the RB protein. Recent studies (Clarke et al., 1992; Jacks et al., 1992; Lee et al., 1992) have shown that mice lacking the RB gene have abnormalities in early brain development suggesting that the rapid rise in RB expression and the hypophosphorylation of the protein are essential for neuronal cell differentiation. PMID- 8502482 TI - The cdk2 kinase is required for the G1-to-S transition in mammalian cells. AB - In the cell cycle of fission and budding yeast, the p34cdc2/CDC28 kinase is required for both the G1-to-S and G2-to-M phase transitions. In vertebrates, the homologous p34cdc2 kinase is required for G2-to-M phase transitions but appears to be dispensable for DNA synthesis. We have investigated the function of a related kinase, p33cdk2, using serum-stimulated quiescent human fibroblasts. While the p33cdk2 protein was expressed at constant levels throughout the cell cycle, p33cdk2 kinase activity was first detected a few hours prior to the onset of DNA synthesis. Microinjection of anti-p33cdk2 antibodies blocked cells from entering S phase. Pre-adsorption of these antibodies with cdk2 protein abrogated their blocking effect suggesting that the G1 arrest caused by these antibodies is cdk2-specific. These results indicate that p33cdk2 is required for the G1-to-S phase transition in mammalian cells. We also show evidence to suggest that the cyclin E/p33cdk2 complex is likely to be required for entry into S phase since the timing of the cyclin E-associated kinase activity was coincident with that of p33cdk2 and preclearing of either component abolished the majority of the histone H1 kinase activity present in the lysates harvested from the late G1. PMID- 8502483 TI - The Fli-1 proto-oncogene, involved in erythroleukemia and Ewing's sarcoma, encodes a transcriptional activator with DNA-binding specificities distinct from other Ets family members. AB - The late stages of the erythroleukemias induced by either the replication defective Friend spleen focus-forming virus (SFFV) or the Friend murine leukemia virus (F-MuLV) are associated with the insertional activation of one of two members (Spi-1 or Fli-1) of the Ets protooncogene family of transcriptional factors. Fli-1 is not rearranged or activated in the erythroleukemias induced by SFFV, and similarly Spi-1 is not rearranged or activated in the leukemic cell clones induced by F-MuLV. This strict specificity of integration sites suggests that Fli-1 and Spi-1 may be functionally distinct and transactivate different downstream genes during the progression of multistage Friend erythroleukemia. In this study, we show that the Fli-1 protein, like other Ets proteins, has DNA binding activity and can act as a sequence-specific transcriptional activator. We also show that the Fli-1 and Spi-1 proteins are functionally distinct in that they recognize and transactivate through distinct DNA binding sites. Furthermore, we have identified an octanucleotide core sequence that is required in vitro for optimal binding of Fli-1 to the Drosophila E74 target and the promoter sequence of the human GPIIB gene. PMID- 8502484 TI - p300, and p300-associated proteins, are components of TATA-binding protein (TBP) complexes. AB - The transforming proteins encoded by the adenovirus E1A gene bind to a 300-kDa cellular product, p300, via the N-terminal E1A sequences. Residues important for p300 binding are required for the transformation function of E1A and for other E1A-mediated gene-regulating functions, including activation of cell cycle regulated products and repression of tissue-specific enhancer activity. Recent evidence indicates that p300 is a DNA-binding protein with specific affinity for known enhancer motifs, suggesting that p300 may be a component of transcription factor complexes. The possibility that upstream element-binding factors might interact with basal transcription factors led us to investigate whether p300 interacts, directly or indirectly, with the TATA-binding protein (TBP). We report here that TBP-specific immunoprecipitations show a 300-kDa protein co precipitating with TBP. This protein is lost from the precipitated material if the lysates are boiled in sodium dodecyl sulfate prior to immunoprecipitation, implying that its presence does not result from non-specific antibody cross reactivity, but is dependent on specific association with TBP. The TBP-associated 300-kDa protein and p300 originally defined by E1A association show indistinguishable partial proteolytic digest patterns, indicating that these are identical or closely related species. Moreover, p300-specific complexes and TBP specific complexes include at least two additional common polypeptide species, phosphoproteins of 64 and 59 kDa. These results suggest that p300 interacts with TBP, possibly through intermediate protein-protein associations. They thus provide additional biochemical evidence for postulated protein-protein interactions between upstream regulatory factors and the basal transcriptional machinery. PMID- 8502485 TI - G1 expression and multistage dynamics of cyclin A in human osteosarcoma cells. AB - Cyclin A was initially characterized as a 'mitotic cyclin', believed to function exclusively at the G2-to-M phase transition; however, recent studies have provided compelling evidence that cyclin A additionally functions earlier in the mammalian somatic cell cycle as a putative 'S-phase-promoting factor'. Moreover, numerous inconsistencies have arisen concerning the temporal induction, subcellular localization, subunit configuration, covalent modification and proteolytic destruction of cyclin A, as well as the physiological function of the cyclin A-associated protein kinase complexes. Utilizing precisely synchronized human MG-63 osteosarcoma cells, the present study demonstrates that cyclin A mRNA and protein are clearly expressed in late G1 prior to S-phase entry, as is cyclin A-associated kinase activity and concomitant phosphorylation of the Rb protein. A series of monospecific cyclin A antibodies were generated and utilized to confirm that multiple covalent modifications of cyclin A occur during the course of the cell cycle, and to characterize the subcellular dynamics in additional detail. Pharmacological blockade with mimosine was utilized to further delineate cyclin A expression and to distinguish the temporal induction from the mechanisms of enzyme activation. Subcellular fractionation and immunocytochemical staining localized nascent cyclin A to the cytoplasm, and revealed a distinct translocation to the nucleus during the G1-to-S phase transition. The results of these studies support a multistage model of cyclin A metabolism and enzyme activation. PMID- 8502486 TI - The Vin-1 gene, identified by provirus insertional mutagenesis, is the cyclin D2. AB - The Vin-1 gene was initially identified as a gene whose expression is altered by the integration of proviruses in the Vin-1 common site of integration in retrovirus-induced rodent T-cell leukemias. We have now isolated the Vin-1 cDNA. Sequencing of the Vin-1 cDNA and Vin-1 exons revealed that the proviruses are integrated at the 5' end of the Vin-1 gene in an inverse transcriptional orientation. The sequence of the Vin-1 gene is identical to that of the recently identified G1-phase cyclin D2 gene. The human homolog of the Vin-1/cyclin D2 gene (CCND2) was mapped to chromosome 12, band p13.3, by in situ hybridization, confirming previous mapping data. Our results strongly support a role of the cyclin D2 gene in oncogenesis and thereby implicate altered cell cycle regulation in transformation. PMID- 8502487 TI - DNA sequence analysis of the major breakpoint cluster region of the BCR gene rearranged in Philadelphia-positive human leukemias. AB - We sought sequence characteristics that might explain the apparent high recombination frequency of the 5-kb BglII segment containing M-bcr exons 1, 2 and 3, and the intron to exon 4. An Alu sequence (subfamily Sx), in 5'-->3' orientation, lay in the middle of a 3-kb region that contains the great majority of Philadelphia chromosome breakpoint sites. The breakpoint of only one out of five chronic myeloid leukemia patients, for whom the BCR breakpoint site had been sequenced, was located within this Alu. Other features of interest for recombination were a 51-bp AT-rich region close to the 3' end, six hypervariable minisatellite consensus octamers, GC[A/T]GG[A/T]GG, six lymphoid recombinase heptamer signal sequences, one nonamer and a 16-bp inverted repeat. Dot matrix comparisons of the 5-kb M-bcr sequence with a 3-kb m-bcr2 segment showed significant homology only in corresponding Alu sequences. PMID- 8502488 TI - Detection of c-mos proto-oncogene expression in human cells. AB - Although the human c-mos proto-oncogene has been characterized for more than a decade, very little is known about its protein product and its expression in somatic cells. We generated three human c-mos-specific antisera and report here the detection of c-mos protein in a human neuroblastoma cell line, SK-N-BE2 (BE2). Both Western (immuno-) blot and immunoprecipitation analyses detected a p37 as the major form and p40 and p35 as minor forms of the c-mos protein. Using Northern blot analysis, 3.5- and 1.7-kb c-mos messages were detected. Using a highly sensitive method that combines reverse transcription and the polymerase chain reaction (RT-PCR), c-mos RNA was detected in all the human samples examined. With Western blot analysis, we further showed that c-mos proteins are expressed in cervical carcinoma-derived cell lines. This ubiquitous expression of low levels of c-mos suggests a fundamental role for the c-mos proto-oncogene. PMID- 8502489 TI - Use of the two-hybrid system to identify the domain of p53 involved in oligomerization. AB - We used a yeast-based genetic assay, the two-hybrid system, to characterize the domain of the tumor-suppressor p53 involved in oligomerization. This assay relies on the reconstitution of the function of a transcriptional activator, the yeast GAL4 protein, via the interaction of a protein fused to the DNA-binding domain of GAL4 with a protein fused to the transcriptional activation domain of GAL4. We show by a reconstruction experiment that this approach could detect the interaction of p53 deleted for its N-terminal activation domain with SV40 large T antigen. We then searched a library of human proteins present as activation domain hybrids for proteins that can interact with the hybrid of p53 with the DNA binding domain. This search identified 36 plasmids containing the p53 gene, representing 10 different classes. These results provide an additional in vivo demonstration of p53 oligomerization. The smallest p53 fragment identified from screening the library contained only amino acids 331-393, indicating that this small C-terminal fragment is sufficient to mediate oligomerization. In addition, a mutant p53 protein could bind to the wild-type protein in this assay, providing support for the idea that mutant forms of p53 act in a dominant-negative manner through C-terminal oligomerization with the wild type. PMID- 8502490 TI - Simple sequence repeat polymorphism within the p53 gene. AB - This report describes a new polymorphism, in intron 3 of the p53 gene, which consists of a single repeat of 16 nucleotides, absent in the published wild-type p53 gene sequence. In the Caucasian population tested (n = 82), 28% of individuals were heterozygotes for this polymorphism. Using PCR-based analysis, we were able to demonstrate p53 allelic losses in three of six breast tumors from heterozygote patients tested. PMID- 8502491 TI - The informatics age is upon us. PMID- 8502492 TI - Metabolic screening in the NICU population: a proposal for change. AB - To be an effective preventive pediatric and public health strategy, newborn screening for hereditary metabolic disorders should include 100% of all neonates as the target population. Delaying screening for critically-ill and premature infants places the neonatal intensive care unit (NICU) population at high risk for developing devastating side effects of untreated or late-treated metabolic diseases. A clinical nursing project was undertaken in The Johns Hopkins Hospital NICU to develop specific metabolic screening criteria for this special population. PMID- 8502493 TI - Disaster preparedness for the ICN: evolution and testing of one unit's plan. AB - A plan for the care of technology-dependent premature and critically ill children during a disaster or other emergency requires more guidance than a generic hospital disaster plan can offer. An intensive care nursery (ICN) devised disaster and emergency preparedness policies and procedures specific to its patient population. Staff responses to events such as loss of power, loss of medical gases, and partial evacuation are described. PMID- 8502494 TI - Parental stressors in a pediatric intensive care unit. AB - Parents experience a variety of stressors when their child is hospitalized in an intensive care unit. Thirty-two parents (10 males and 22 females) of children in the pediatric intensive care unit of a children's hospital were surveyed using a revised version of the Carter and Miles (1983) Parental Stressor Scale: Pediatric ICU (PSS:PICU) and one open-ended question to identify their most significant stressors. Some findings agreed with those from previous studies; other results differed. Differences in some areas in fathers' and mothers' perceptions were noted. Two concerns reported were the differences of doctors' opinions regarding the child's care and parents not being able to continually stay with their child. PMID- 8502495 TI - Mothers' stress and close relationships: correlates with infant health status. AB - This descriptive follow-up study focuses on changes in maternal stress and close relationships over the infant's first year and explores the association of these maternal variables with infant health status. After initial interviews at 1 month, mothers of 43 infants completed a follow-up questionnaire when their infants were 13 months old. Women tended to select their husbands or mothers as their closest relations, and 9 women noted that their closest person at 13 months was a different person than at 1 month. Infant hospitalization, but not risk status or major illness in the infant, was significantly related to maternal stress and relationship change. The association among infant hospitalization, greater maternal stress, and less closeness in relationships support the importance of focusing on the whole family in the hospital setting. PMID- 8502496 TI - Understanding the basics of beta thalassemia major. AB - beta thalassemia major, a severe genetic disorder of the red blood cell, affects about 1,400 people in the United States, including children. Clinical management of this disorder has improved significantly in recent years, and ongoing research will lead to an even brighter outlook in the future. PMID- 8502497 TI - The health care safety net. PMID- 8502498 TI - Flumazenil (Mazicon) PMID- 8502499 TI - Home management related to medical treatment for childhood gastroesophageal reflux. AB - Parents caring for a child with gastroesophageal reflux are at risk for impaired home maintenance management because of the challenges they face such as the emotional impact, financial concerns, and difficulty maintaining the strict regime. Nursing interventions related to family education and support assist the families in becoming knowledgeable and compliant while fostering normal growth and development. PMID- 8502501 TI - When parents demand "everything". AB - Critical care professionals may be faced with requests by parents to continue life-sustaining treatment despite professional recommendations to the contrary. Such cases raise complex moral, legal and social issues that require ongoing ethical dialogue in hopes of achieving a social consensus. Professional standards, a statutory framework, case law and the exercise of professional and parental responsibility will also play a role in this dialogue. PMID- 8502502 TI - Pediatric management problems: urinary tract infection. PMID- 8502500 TI - A comparison of growth patterns in breast and bottle-fed infants with congenital heart disease. AB - PURPOSE: To describe the feeding and growth patterns of breast and bottle-fed infants with congenital heart disease. METHODOLOGY: A descriptive correlational design was used to examine relationships between incidence of breast feeding, severity of disease, and patterns of weight gain for 45 mother-infants dyads. FINDINGS: Using chi square analysis, length of hospital stay was found to be significantly related to the decision to switch from breast to bottle feeding. Bottle-fed infants fell significantly off their individual growth curves than did breast-fed infants. CONCLUSIONS: Severity of cardiac defect was not a predictor of the infant's ability to breast feed nor of the duration of breast feeding after discharge. Maternal variables may account for initial failure of breast feeding. PMID- 8502503 TI - Documenting the primary nursing summary note: a leap toward professionalism. AB - A newly developed documentation tool greatly enhances professional nursing practice, empowerment, and interdisciplinary collaboration. The Primary Nursing Summary Note captures the essence of the nursing process, records and validates it in the interdisciplinary patient progress notes, and facilitates the provision of high quality, cost-effective health care. PMID- 8502504 TI - A rare complication of pediatric catheterization. AB - Catheterization is a safe and effective nursing intervention that is taught to almost every nursing student in the country. Most of the complications students are encouraged to prevent include: infection, skin irritation, trauma due to failing to release the bubble when removing the catheter, and obstruction. Rarely are additional problems encountered. Case studies can often alert us to the possibility of rare and unanticipated complications. The following is an example of just such a case study. PMID- 8502505 TI - Future of pediatric advanced practice nursing. PMID- 8502506 TI - Antenatal corticosteroids appear to reduce the risk of postnatal germinal matrix hemorrhage in intubated low birth weight newborns. AB - OBJECTIVE: To determine to what extent the reduced risk in preterm newborns of intracranial hemorrhage attributed to antenatal corticosteroids (ANCS) reflects reductions in the incidence of respiratory distress and its correlates. METHODS: In a sample of 239 very low birth weight newborns recruited for a clinical trial of phenobarbital prophylaxis of subependymal/intraventricular hemorrhage, we explored the relationship between ANCS, the occurrence of germinal matrix hemorrhage (GMH) that first became evident after the 12th postnatal hour, and putative intervening variables such as acidosis, elevated peak inspiratory pressure, pneumothorax-pulmonary interstitial emphysema, and elevated continuous positive airway pressure. RESULTS: In multivariate models adjusting for confounders, newborns exposed to ANCS were at approximately one third the risk of GMH experienced by newborns not exposed to a full course of ANCS. The additions of measures and correlates of respiratory distress severity to these models did not change the GMH risk associated with ANCS. CONCLUSION: The GMH-protective effect of ANCS does not appear to be a consequence of enhanced pulmonary maturation. PMID- 8502507 TI - Effects of time-in-clinic, clinic setting, and faculty supervision on the continuity clinic experience. AB - STUDY OBJECTIVE: To evaluate the effects of setting, type of supervision, and time in clinic on the resident continuity clinic experience. DESIGN: Prospective cohort with preintervention and postintervention measures. SETTINGS: Pediatric residents selected one of three clinic settings for their continuity clinic experience. These included a traditional, university-based clinic, private practice offices, and publicly funded community-based clinics. SUBJECTS: All pediatric residents at the University of Utah Health Sciences Center, July 1985 through June 1991. INTERVENTIONS: Using varied clinic sites, matching residents one or two to one with preceptors for their continuity clinic, increasing continuity clinic from 1 to 2 half-days per week. MEASUREMENTS AND MAIN RESULTS: Residents in private offices had the most varied experience, seeing more patients, more acute care, and a broader age range of patients than residents at other sites. They were more likely both to be observed by their preceptors during patient visits and to observe their preceptors delivering care. Because the number of patients seen per session rose, increasing continuity clinic time from one to two half-days per week more than doubled the number of patients seen per week. Increased time away from hospital did not affect scores on the Pediatric In Training Examination. While test scores were similar for incoming residents, those in private offices scored higher on the final Behavioral Pediatrics Examination (P < .05). CONCLUSIONS: Clinic setting, time in clinic, and faculty supervision affect the quality of the continuity clinic experience. Increased time in clinic resulted in a broader exposure to patients. Residents placed in private offices had a more varied patient mix, were more closely supervised, and seemed to gain primary care skills more rapidly than residents at other sites. PMID- 8502508 TI - Impact of improved survival of very low birth weight infants on recent secular trends in the prevalence of cerebral palsy. AB - OBJECTIVE: To review recent secular trends in the prevalence of cerebral palsy in industrialized countries that have population-based cerebral palsy registries and to estimate such time-trends for the United States, where until recently such registries were absent. DATA SOURCES: Recent epidemiologic studies of cerebral palsy published in peer-reviewed journals in English, and US vital data bearing on the principal demographic determinants of cerebral palsy--birth rates, the birth weight distributions, birth weight-specific mortality risk, and cerebral palsy risk among survivors. RESULTS: Most epidemiologic studies from industrialized countries show a rise in the childhood prevalence of cerebral palsy in recent decades, largely because of the increasing contribution of children of low and very low birth weight to its prevalence. The only demographic determinant of cerebral palsy prevalence that is changing rapidly in the United States is survival of low birth weight and very low birth weight infants. Based on the magnitude of change in the survival of low and very low birth weight infants, it is estimated that childhood prevalence of cerebral palsy rose about 20% between 1960 and 1986 in the United States. CONCLUSION: An apparently unavoidable side effect of the increasing success of newborn intensive care is a moderate rise in the childhood prevalence of cerebral palsy. PMID- 8502510 TI - An environmental intervention to reduce dietary fat in school lunches. AB - OBJECTIVE: To determine whether making a low-fat entree available as one of two choices in an elementary school lunch program would reduce the fat content of meals selected by children. DESIGN: In this before-after trial, students had a daily choice between two entrees, one of which was sometimes low-fat. For 93% of school days during 14 consecutive school months, daily entree choices were recorded for 619,976 student meals. The fat content of entrees was assessed with a computerized nutrient database supplemented by food manufacturer's data. SETTING: Sixteen elementary schools in the Bellevue (Washington) School District. PARTICIPANTS: The number of students eating school lunch averaged 2440 per day, of whom 25% were less than 185% of poverty. INTERVENTION: After a baseline period of 6 months, the intervention increased the number of days per month when one of the two entrees had 30% or fewer calories from fat. MAIN OUTCOME MEASURES: Data for the entire district were combined to estimate for each month the percent of students who selected low-fat entrees and the percent of calories from fat in the average meal selected by students. RESULTS: During the 6 months before the intervention, a low-fat entree was available on 23% of days; it was selected by 39% of students; and the average meal selected by students had 36% of calories from fat. By the end of the 8-month intervention, a low-fat option was available on 71% of days; it was selected by 29% of students; and the fat content of the average meal dropped from 36% to 30% of calories from fat (P = .02). CONCLUSIONS: In this school district, many students, given the choice, selected low-fat entrees. Recommendations for dietary fat were met simply by the environmental intervention of increasing the availability of low-fat foods. PMID- 8502509 TI - Placebo-controlled evaluation of Ritalin side effects. AB - OBJECTIVE: To address the frequency of side effects of Ritalin therapy in children with attention deficit hyperactivity disorder (ADHD) using the Barkeley Side Effects Questionnaire (BSEQ) in a clinical setting. DESIGN: Randomized double-blind placebo-controlled cross-over trial. SETTING: A large rural tertiary care clinic. PATIENTS: 234 consecutive children aged 5 through 15 years who met the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) criteria for ADHD were enrolled. Of these children, 206 had sufficient side effects data for analysis. INTERVENTIONS: 0.3 mg/kg per dose and 0.5 mg/kg per dose Ritalin compared to placebo in separate 2-week trials. Each treatment was given three times a day for 7 consecutive days. MEASUREMENTS AND MAIN RESULTS: Parents, blinded to the treatment assignment, assessed side effects via the BSEQ at baseline and at the end of each of the 4 treatment weeks. Univariate odds ratios (OR) were used to describe the magnitude of differences in observed side effects between Ritalin and placebo weeks of the trial for each of the items on the BSEQ. The frequency of the following side effects significantly increased with Ritalin therapy: insomnia (OR = 3.13, 95% confidence interval [CI] = (1.80,5.42)), appetite disturbance (OR = 19.00, 95% CI = (9.18,39.31)), stomachache (OR = 7.00, 95% CI = (3.29, 14.89)), headache (OR = 5.29, 95% CI = (2.51,11.15)), and dizziness (OR = 7.50, 95% CI = (1.93,29.13)). The frequency of the following side effects significantly decreased with Ritalin therapy: staring and daydreaming (OR = 0.47, 95% CI = (0.27,0.84)), irritability (OR = 0.33, 95% CI = (0.18,0.61)), anxiety (OR = 0.42, 95% CI = (0.23,0.76)), and nailbiting (OR = 0.19, 95% CI = (0.07, 0.53)). The incidence rates of the remaining BSEQ items did not differ significantly between the Ritalin and placebo weeks of the trial. CONCLUSION: The BSEQ proved to be clinically effective in tracking Ritalin side effects and should be incorporated into the routine evaluation and monitoring of ADHD patients for whom stimulants are prescribed. PMID- 8502512 TI - The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. AB - OBJECTIVE: The objective of this study was to address the need for early diagnosis of Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome characterized by a unique cellular hypersensitivity to DNA cross-linking agents, such as diepoxybutane, and by a high risk of malignancies. METHODS: We analyzed data from 370 FA patients enrolled in the American Registry of the International FA Registry. Of these individuals, 220 had congenital malformations; the rest were ascertained based on hematologic abnormalities only or on clinical evaluation and screening following the diagnosis of an affected family member. The probands noted to have congenital malformations at the time of diagnosis were classified into two groups on the basis of their clinical presentation: (1) patients manifesting both congenital malformations and hematologic abnormalities (159 individuals); (2) patients manifesting congenital malformations only (61 individuals). RESULTS: The mean age of diagnosis was 6.6 years and 1.1 years for Groups 1 and 2, respectively. Thus, the majority of FA patients with congenital malformations were not diagnosed until after the onset of hematologic abnormalities. We also report central nervous system, gastrointestinal, and skeletal malformations which previously have not been included as part of the FA phenotype. Our review of the patients enrolled in the International FA Registry indicates that the FA phenotype is more variable than recognized previously. CONCLUSIONS: Testing for sensitivity to diepoxybutane to rule out a diagnosis of FA needs to be applied more widely in patients with congenital malformations. All siblings of affected probands also should have testing, because a lack of concordance of phenotype in affected siblings makes clinical diagnosis unreliable even within sibships. A more timely diagnosis of FA in the preanemic phase is needed to implement appropriate therapy and to enable parents to make informed reproductive decisions. PMID- 8502511 TI - Prone or supine body position and sleep characteristics in infants. AB - OBJECTIVE: To evaluate the potential relation between body position and sleep characteristics in normal infants. PATIENTS: Two groups of 3-month-old healthy infants were evaluated: 40 infants who usually slept supine, and 40 who usually slept prone. The two groups were matched for gender, gestational age, postnatal age, birth weight, and total recording time. RECORDING TECHNIQUES: The 80 infants were studied polygraphically during one night in the pediatric sleep laboratory. They were allowed to fall asleep in their usual sleep position, and every 3 hours were gently turned from prone to supine, or from supine to prone. RESULTS: In each group, 6 infants were excluded from the analysis, because they woke up after having been turned over. In both groups, no significant difference was seen between the prone and the supine body positions for the following variables: number of sleep state changes; number of gross body movements; percent of rapid eye movement sleep; saturation with oxygen, arterial blood levels; number and duration of acid esophageal reflux; rectal temperature; mean respiratory rates; water evaporation rates from the forehead skin; and number or duration of central or of obstructive apneas. In both groups of infants, prone body position was associated with a significant increase in sleep duration (+16%) and in non-rapid eye movement sleep (+25%) and a significant decrease in number of arousals (-40%) and in their duration (-43%). CONCLUSIONS: No explanation has been found for the sleep-promoting effect of prone body positioning. The finding could be of interest to the study of infants' sleep quality, as well as to the potential relation between body positions and sudden death during sleep. PMID- 8502513 TI - Long-term effect of inhaled corticosteroids on growth rate in adolescents with asthma. AB - BACKGROUND: Growth in stature in asthmatic adolescents may be delayed compared to normals as a result of treatment with inhaled corticosteroids (CS) or because of a delay in puberty. However, growth rates in asthmatic children have never been studied when treatment with CS was randomized and when growth was compared with that of matched healthy control subjects. OBJECTIVE: To assess the long-term effect of CS treatment on growth rates in asthmatic adolescents. METHODS: Participants were 40 asthmatic teenagers (mean age 12.8 years) who received randomized treatment with 0.2 mg of albuterol (salbutamol) with either placebo three times a day (BA + PL) or 0.2 mg of budesonide three times a day (BA + CS) for a median period of 22 months in a double-blind controlled study. Growth rates were compared with those of 80 control subjects who were matched for sex, age, height, and duration of follow-up. RESULTS: Growth rates in male patients, but not in female patients, were significantly less than in control subjects (P < .05), a finding consistent with a delay of puberty due to asthma. The mean difference (95% confidence interval) in growth rates between patients treated with BA+PL and their controls was -0.70 (-1.62, 0.22) cm/y; that between patients treated with BA + CS and their controls was -0.44 (-1.25, 0.37) cm/y. The observed mean (SEM) case-control difference between treatment groups was +0.27 (0.58) cm/y in favor of BA + CS. CONCLUSION: Growth retardation observed in adolescents with asthma may be due to a delay in puberty but not to the prescription of 0.6 mg of budesonide daily. PMID- 8502515 TI - Long-term psychosocial sequelae of chronic physical disorders in childhood. AB - OBJECTIVE: This study was designed to examine the long-term psychosocial sequelae of chronic physical disorders that begin during childhood. DESIGN: We analyzed data from a national birth cohort. 12,537 children were followed until age 23 years--76% of all born in Britain during one week in 1958. Of these, 1667 had a chronic disorder before age 16 and 1279 were included in the 23-year follow-up. MEASURES: Outcome measures included self-reported psychological disturbances between ages 16 and 23, scores on the Malaise Inventory, social class, educational qualifications, unemployment, and social activities. RESULTS: The total cumulative incidence rate before 16 years was 109.5 per 1000. Demographic comparisons showed that the group with chronic physical disorders was similar to those free of chronic disorders in all respects except the sex ratio. Men with chronic physical disorders had significantly higher relative risks for abnormal scores on the Malaise Inventory (1.52, confidence interval [CI] 1.13, 2.05); specialist psychological care (1.43, CI 1.00, 2.03); poor educational qualifications (1.26, CI 1.08, 1.47); periods of unemployment (1.20, CI 1.03, 1.41); and less social drinking (1.36, CI 1.15, 1.60). In contrast, women only had a significantly elevated risk for having seen a mental health specialist (1.32, CI 1.02, 1.71). Among the men some of the risks were further elevated for those in specific diagnostic groups. These findings are examined in the light of postulates about the impact of chronic physical disorders as a whole and in an attempt to explain the striking sex differences. For clinicians they provide further reason to justify concern about the psychosocial aspects of care for children with chronic disorders. PMID- 8502514 TI - Estimation of central osteopenia in children with chronic polyarthritis treated with glucocorticoids. AB - STUDY OBJECTIVE: To investigate the degree and determinants of osteopenia in juvenile chronic polyarthritis. DESIGN: Retrospective case-control study of central bone mineral density. SETTING: Rheumatism Foundation Hospital and Kuopio University Hospital, Finland. SUBJECTS: A sample of 43 girls aged 7 to 19 with juvenile chronic polyarthritis treated with systemic glucocorticoids and a control sample of 44 healthy girls matched for age. MAIN OUTCOME MEASURES: Bone mineral density and bone size (width) measured by dual-energy x-ray absorptiometry and bone volumetric density calculated as an approximation of true bone density at both the lumbar spine and femoral neck. RESULTS: The girls with juvenile chronic arthritis had reduced bone mineral density, bone size, and bone volumetric density at both the lumbar spine and femoral neck (statistically significant findings, P = .022 for the bone size of the femoral neck and P < .001 for the other parameters). At the spine, the mean bone mineral density was 80%, the mean bone size 89%, and the mean bone volumetric density 89% of the values in the control group. At the femoral neck, the values were 78%, 93%, and 83%, respectively. The groups were matched for age, but the girls with arthritis were smaller and lighter. In the juvenile arthritis group, the femoral bone mineral density and bone volumetric density and the spinal bone width correlated negatively with the mean glucocorticoid dose. CONCLUSION: Axial bone mineral density is clearly reduced in severe juvenile polyarthritis and is mediated by both decreased bone volumetric density and diminished growth. PMID- 8502516 TI - Monitoring premature infants in car seats: implementing the American Academy of Pediatrics policy in a community hospital. AB - OBJECTIVES: In 1990, the American Academy of Pediatrics (AAP) Committee on Injury and Poison Prevention issued a policy statement which recommended that all infants born at less than 37 weeks gestational age be monitored in their car seat before discharge to identify infants at risk for apnea associated with car seat use. The objective of this report is to summarize the experience of a community hospital in implementing this recommendation, including: education of health professionals about the problem and its management, development of an effective hospital policy and procedure for testing at-risk infants, overcoming logistical difficulties for nursing staff who implement the policy, overcoming liability concerns, and summarizing the clinical results which we observed during a 15 month period. METHODS: MetroWest Medical Center, Framingham Union Campus is a community hospital with a Level II Neonatal Unit with approximately 2200 deliveries annually. Hospital procedures and policies were developed to implement the AAP policy for safe transportation of premature infants. Consequently, infants less than 37 weeks gestation at birth were monitored for a 90-minute observation period for oxygen saturation, apnea, or bradycardia in the car seat that they would be going home in from the nursery. RESULTS: Policies and procedures for car seat monitoring were instituted successfully during 15-month period. Sixteen of 87 (18.4%) monitored infants 26 to 36 weeks gestation had abnormal results. In addition, one 37-week gestational newborn who was monitored because of duskiness during feeds also became apneic and bradycardic in the car seat. CONCLUSIONS: A car seat monitoring program can be incorporated effectively into a Level II community hospital nursery discharge plan provided that appropriate medical staff policies, nursing procedures, and administrative support to deal with the logistics of the program is established. Our monitoring results are consistent with previous reports that premature infants are at risk of desaturation in a car seat. In addition, we have demonstrated that a full-term neonate may also be at risk if other evidence of desaturation (eg, duskiness during feedings) is observed. PMID- 8502517 TI - Efficacy of albumin and diuretic therapy in children with nephrotic syndrome. AB - OBJECTIVE: To examine the efficacy and complications of albumin and diuretic therapy in the treatment of edema due to the nephrotic syndrome. METHODS: The clinical and biochemical effects of 35 treatment courses of albumin and diuretics administered to 21 children with nephrotic syndrome were retrospectively examined. Treatment consisted of intravenous infusion of 25% albumin and furosemide. A second diuretic was administered in addition to furosemide during 10 treatment courses. There was an average of 5 infusions per hospitalization. RESULTS: Albumin and furosemide therapy resulted in a 1.2 +/- 0.2% (SEM) body weight loss per infusion. The administration of albumin with two diuretics did not result in improved weight loss compared to albumin and furosemide alone. Patients whose nephrotic syndrome was in remission at the time of posthospitalization follow-up (n = 8) had a sustained weight loss both during and after albumin and diuretic treatment. Patients with persistent proteinuria (n = 27) transiently lost weight during therapy, but returned to a weight similar to their pretreatment weight at 2-week follow-up. Albumin infusion resulted in hypertension, requiring acute antihypertensive therapy in 16 treatment courses (46%) and increased maintenance antihypertensive therapy in 12 treatment courses (34%). In addition, hypokalemia, hypernatremia, and hyperbicarbonatemia developed in 40%, 17%, and 11% of treatment courses, respectively. Albumin and diuretic therapy resulted in the development of respiratory distress during four treatment courses, including one patient who developed respiratory failure and one patient who developed congestive heart failure. CONCLUSIONS: Albumin and diuretic therapy results in fluid removal and weight loss in children with the nephrotic syndrome; however, this effect is transient unless remission of proteinuria occurs. While this is a retrospective study, the findings suggest that albumin and diuretic therapy can be associated with frequent and potentially serious complications. PMID- 8502518 TI - Coagulopathy screening in children with heparinized central venous catheters. AB - OBJECTIVE: To develop a method of screening for coagulopathy using blood drawn through heparinized central venous catheters. METHODS: Prothrombin time (PT) and activated partial thromboplastin time (APTT) were determined in paired blood samples with and without the addition of protamine, using an automated photo optical method. A concentration of 4 micrograms/mL of citrated whole blood was chosen, based on preliminary experiments. This is sufficient to neutralize the expected heparin contamination in samples drawn through heparinized catheters while causing only a slight prolongation in APTT (due to the anticoagulant effect of protamine). Seventeen paired samples were drawn by venipuncture in patients without known coagulopathy. Twenty-five samples were drawn through heparinized central venous catheters. The first 5 mL of blood drawn from a catheter was discarded to avoid gross heparin contamination. Four samples from patients with coagulopathy were also analyzed with and without the addition of 2.5 micrograms/mL of heparin. RESULTS: Protamine increased PT by 9.0 +/- 0.8% and APTT by 9.0 +/- 3.4% (mean +/- SD) in the samples drawn by venipuncture. For samples drawn through heparinized catheters, 52% had a prolonged APTT, 44% a prolonged PT, and 68% had at least one prolonged test. With the addition of protamine, and after correction for the 9% mean increase in PT and APTT, 4% of samples had a prolonged APTT, 12% had a prolonged PT, and 16% had at least one prolonged test (P = .00006, .014, and .0001). All four samples from patients with coagulopathy were correctly identified as abnormal after the addition of protamine, with or without added heparin. CONCLUSIONS: A protamine-supplemented APTT test on blood drawn through a heparinized catheter may be an adequate screening test for coagulopathy. This procedure reduces discomfort in patients with an indwelling catheter by avoiding venipuncture. PMID- 8502519 TI - Bone mineral content in infants and children with chronic cholestatic liver disease. AB - OBJECTIVE: To assess bone mineral content (BMC) status and serum vitamin D metabolite levels of infants and children with chronic cholestatic liver disease. To determine if severity of bone disease in these patients correlates with serum vitamin D metabolite levels. METHODOLOGY: We measured radial BMC with the use of a single-beam photon absorptiometer and serum vitamin D metabolite levels in 56 patients with chronic cholestasis seen at our institution from 1985 through 1991. Patients were divided into two groups according to age. RESULTS: In group 1 (n = 37; age 2 to 22 months), decreased levels of BMC were seen as early as the first few months of life, with sharp decline observed with increasing age (approaching 3 to 5 standard deviations [SD] below the mean, P < .0003). Older patients (group 2, n = 19; age 2 to 20 years) had BMC values which clustered between 2 and 4 SD below the mean throughout the age range. Although a downward trend also was noted with increasing age, this was not statistically significant. Despite correction for weight-age or height-age, BMC was decreased in most of these patients. No correlation between severity of osteopenia and serum levels of 25(OH)-vitamin D and 1,25(OH)2-vitamin D was observed in either infants or older children. CONCLUSIONS: Decreased bone mineralization, as a complication of chronic cholestatic conditions, is a disease process that begins early in infancy, rapidly worsens with increasing age and hepatic dysfunction, and remains relatively stable in children with more stable liver disease. PMID- 8502520 TI - Accuracy and precision of low-dose insulin administration. AB - OBJECTIVE: To determine the lowest dose of concentrated (U100) insulin that can be reproducibly delivered. METHODS: A telephone survey was used to determine current practices in major pediatric hospitals regarding the administration of low doses of concentrated insulin. A sensitive gravitometric technique was used to determine the error in measurement of low doses of U100 insulin by pediatric nurses and parents of diabetic children. RESULTS: A telephone survey revealed that doses as low as 0.5 or 1.0 U (5 to 10 microL) are routinely administered in pediatric hospitals. In our study of pediatric nurses, attempts to deliver 0.5, 1.0, and 2.0 U resulted in delivered doses of 0.975 +/- 0.315, 1.638 +/- 0.376, and 2.153 +/- 0.435 U (mean +/- standard deviation of the mean), respectively. The use of 0.3-mL syringes compared to 0.5-mL syringes did not improve accuracy or precision. Taken as a group, parents of children with diabetes were more accurate (mean delivered dose of 1.063 +/- 0.276 for the 1-U dose), but the individual means ranged from 0.641 to 1.300 and coefficients of variation ranged from 5% to 33%. Only three of the seven parents could deliver 1.0 U with acceptable precision and accuracy. CONCLUSIONS: When currently available syringes are used, insulin injections of less than 20 microL (2 U of U100) have an unacceptably large error. It is recommended that, in the inpatient setting, diluted insulin be used if the prescribed dose is less than 2.0 U. PMID- 8502522 TI - Duration of positive throat cultures for group A streptococci after initiation of antibiotic therapy. AB - OBJECTIVE: To determine if it is appropriate to recommend that patients with group A beta-hemolytic streptococcal pharyngitis, who are clinically well by the morning after starting antibiotic treatment, can return to school or day care, or if they should wait until they have completed 24 hours of antibiotics as recommended by the American Academy of Pediatrics Committee on Infectious Diseases. METHODS: We examined the duration of positivity of the throat culture after antibiotics were begun as a means of assessing the potential risk of transmission to close school contacts. Forty-seven children (4 to 17 years of age) with pharyngitis and a positive throat culture for group A streptococci in an outpatient, staff model health maintenance organization clinic were enrolled and were randomly selected to receive therapy with either oral penicillin V, intramuscular benzathine penicillin G, or oral erythromycin estolate. Additional throat cultures were obtained and clinical findings were recorded for each child during three home visits in the 24 hours after their initial clinic visit. Acute and convalescent sera were obtained for determination of anti-streptolysin O and anti-DNase B titers. RESULTS: Seventeen (36.2%) of the 47 patients had a positive culture the morning after initiating antibiotic therapy. However, thirty-nine (83%) of the patients became "culture negative" within the first 24 hours. Neither the time interval to the first negative culture nor the presence or absence of group A streptococcal organisms on any single convalescent culture could be predicted by clinical findings. Six of the eight children who failed to convert to a "negative" throat culture within 24 hours of initiating therapy were receiving erythromycin. We could detect no difference in either time to conversion to a negative culture or the presence of a positive culture 24 hours after starting antibiotics between those who demonstrated a significant antibody increase and those who did not. CONCLUSION: The data from this study strongly suggest that children with group A beta-hemolytic streptococcal pharyngitis should complete a full 24 hours of antibiotics before returning to school or daycare. PMID- 8502521 TI - Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying. AB - OBJECTIVE: The pathophysiology of severe reactions to diphtheria-tetanus pertussis (DTP)vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied. DESIGN: Prospective, referral-based surveillance. SETTING: Los Angeles, CA. SUBJECTS: Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization. OUTCOME MEASURES: A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states. RESULTS: Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever > or = 40.5 degrees C only, 4 subjects had persistent crying > or = 3 hours, 6 children had seizures and fever > or = 40.5 degrees C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (> or = 38 degrees C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions. CONCLUSIONS: Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions. PMID- 8502523 TI - Attitudes of mothers, doctors, and nurses toward neonatal intensive care in a developing society. AB - BACKGROUND: The ethical allocation of scarce resources is a major challenge for physicians working in the developing world. Guidelines currently employed by health care workers in the developed world may be considered impractical or inappropriate in the "Third World." OBJECTIVE: To gain insight into the attitudes of doctors, nurses, and mothers of recent neonatal intensive care unit (NICU) survivors toward the utilization and withdrawal of life support in the context of a developing society. DESIGN: Descriptive cohort study. PARTICIPANTS: Thirty three doctors, 20 nurses, and 70 mothers of recent NICU survivors. The cohort of mothers surveyed were predominantly unmarried, poorly educated, and either unemployed or still at school. RESULTS: In response to hypothetical scenarios, mothers exhibited very conservative attitudes toward withdrawal of life support compared to caregivers. Only 2.9% (2/70) of mothers would contemplate any degree of life support withdrawal for infants with probable "moderate" handicap compared with 51.0% (26/51) of the medical staff. One mother (1.4%, 1/70) accepted the concept of withdrawal of life support where extremely poor outcome was anticipated, compared with 85% (45/53) of the caregivers. Doctors and nurses exhibited very utilitarian attitudes toward NICU resource allocation, with emphasis directed toward avoidance of significant handicap. The majority of these caregivers considered the anticipated burden of the handicapped child in the society to be a major factor in the justification of their decision. CONCLUSION: The nonideal conditions under which doctors and nurses work in developing nations mandate resource allocation to be an integral component of NICU care. PMID- 8502524 TI - Measles severity and serum retinol (vitamin A) concentration among children in the United States. AB - BACKGROUND: Studies in developing countries have shown that children with measles have low serum retinol concentrations and that lower retinol levels are associated with measles-related mortality. Vitamin A therapy has been shown to reduce mortality among African children with acute measles. OBJECTIVES: To determine whether serum retinol concentration is low among children with measles in the United States and to determine whether retinol concentration is associated with illness severity. SETTING: Pediatric referral hospital and clinic in Milwaukee, WI, during the measles outbreak of 1989-1990. PATIENTS: One hundred fourteen patients < or = 5 years of age evaluated for serologically confirmed measles with serum obtained within 5 days following rash onset. METHODS: Serum retinol concentration was determined by high-performance liquid chromatography. Clinical data were collected by hospital record review. A modified Pediatric Risk of Mortality (PRISM) score was used to assess physiologic instability as a measure of illness severity. RESULTS: Retinol concentrations ranged from 0.25 to 1.18 mumol/L (median 0.58 mumol/L); 82 (72%) patients had low retinol concentration (< or = 0.70 mumol/L). Median retinol concentrations were lower among hospitalized patients (0.56 vs 0.70, P = .006) and patients with pneumonia (0.52 vs 0.64, P = .02) but higher among children with otitis media (0.63 vs 0.54, P = .01). Higher modified PRISM scores, reflecting greater physiologic instability, were associated with lower retinol concentration (beta coefficient .0147, P = .025). In multivariate analysis, higher modified PRISM scores were associated with lower retinol concentration (beta coefficient -.0144, P = .025) even after controlling for hospitalization, presence of complications, race, age, receipt of Aid to Families With Dependent Children, gender, and interval from rash onset until serum was collected. CONCLUSIONS: Among these children with measles in an urban United States community, retinol concentrations were depressed, and the degree of depression was associated with illness severity. Vitamin A therapy should be considered for children with measles in the United States who require hospitalization. PMID- 8502525 TI - Self-medication in childhood: observations at a residential summer camp. PMID- 8502526 TI - Establishment of primary care continuity experiences in community pediatricians' offices: nuts and bolts. PMID- 8502527 TI - Childhood sexual abuse reported by facilitated communication. AB - Facilitated communication remains an unproven and controversial strategy for nonspeaking children with developmental disabilities. It is possible that the process may be influenced by the facilitator. The evaluation of alleged sexual abuse reported by FC must include a full psychosocial history, complete physical examination for evidence of abuse, and the assessment of the child's communicative competence. The demonstration of communicative competence requires a strategy similar to that utilized with Carla. The successful documentation of the child's communication of general information should precede the pursuit of specific abuse issues. PMID- 8502528 TI - Congenital microgastria and limb reduction defects. PMID- 8502529 TI - Blue sclerae: a sign of iron deficiency anemia in children? PMID- 8502530 TI - Phenolphthalein-induced fixed drug eruption: a cutaneous complication of laxative use in a child. PMID- 8502531 TI - Compartment syndrome following intraosseous infusion. PMID- 8502532 TI - American Academy of Pediatrics AAP Section on Endocrinology and Committee on Genetics, and American Thyroid Association Committee on Public Health: Newborn screening for congenital hypothyroidism: recommended guidelines. PMID- 8502533 TI - American Academy of Pediatrics Committee on Environmental Health: Ambient air pollution: respiratory hazards to children. PMID- 8502534 TI - Who doesn't know this. PMID- 8502535 TI - Self-regulation of energy intake in children, questioned. PMID- 8502536 TI - Preventing lead poisoning in kids: a win-win opportunity. PMID- 8502537 TI - Helicobacter pylori in children with acquired immunodeficiency syndrome. PMID- 8502538 TI - Which is the most appropriate dosage of liposomal Amphotericin-B (AmBisome) for the treatment of fungal infections in infants of very low birth weight? PMID- 8502539 TI - Bilirubin and brain toxicity in neonates: dead but won't lie down? PMID- 8502540 TI - On the association of unilateral thalamic hemorrhage and urinary tract infection. PMID- 8502541 TI - The lead debate goes on. PMID- 8502542 TI - Genomic targeting with purified Cre recombinase. AB - Purified Cre recombinase protein introduced directly into cultured mammalian cells by lipofection catalyzes both site-specific chromosomal integration of a co transfected lox targeting vector and precise excision of genomic DNA flanked by directly repeated lox sites. This procedure eliminates the need to transfect cre expression plasmids to activate recombination at lox sites. We used this simplified procedure to investigate the effect on targeting efficiency of both lox vector design and chromosomal position of the lox target. We show that such chromosomal position effects can exert at least a 50-fold per lox target difference in targeting efficiency in a human osteosarcoma cell line. PMID- 8502544 TI - The identification of hydroxymethyluracil in DNA of Trypanosoma brucei. AB - We have previously reported the detection of two unusual nucleotides, pdJ and pdV, in the DNA of Trypanosoma brucei (Gommers-Ampt et al., 1991). pdJ was found to be a novel nucleotide and is possibly involved in the regulation of variant specific surface antigen gene expression in trypanosomes. Recent evidence suggests that V could be a precursor of J, making V a key compound in the study of the biosynthesis and function of J. We have therefore determined the structure of V and here we present proof that V is HOMeU. The identity is based on a detailed comparison of dV(p) with authentic HOMedU(p), showing: I) co-migration in three different liquid chromatography analyses II) identical UV absorbance characteristics III) identical behavior in acetyl-pentafluorobenzyl derivatization and subsequent Gas chromatography/Mass spectrometry (GC/MS). The GC/MS technique has not been used before to analyse HOMedU purified from biological material. Because of its high sensitivity, it may also be useful for the detection of the low amounts of HOMedU resulting from oxidative damage of DNA. PMID- 8502543 TI - Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure. AB - Deprotection of methylphosphonate oligonucleotides with ethylenediamine was evaluated in a model system. Methylphosphonate sequences of the form 5'-TTTNNTTT, where N was either N4-bz-dC, N4-ibu-dC, N2-ibu-O6-DPC-dG, N2-ibu-dG, N6-bz-dA, or T, were used to determine the extent of modifications that occur during deprotection. Up to 15% of N4-bz-dC was found to transaminate at the C4 position when treated with ethylenediamine. A similar displacement reaction with ethylenediamine was observed at the O6 position of N2-ibu-O6-DPC-dG, and to a much lesser extent of N2-ibu-dG. Side reactions were not observed when oligonucleotides containing N4-ibu-dC, N6-bz-dA, or T were treated with ethylenediamine. A novel method of deprotecting methylphosphonate oligonucleotides was developed from these studies. The method incorporates a brief treatment with dilute ammonia for 30 minutes followed by addition of ethylenediamine for 6 hours at room temperature to complete deprotection in a one pot format. The solution is then diluted and neutralized to stop the reaction and prepare the crude product for chromatographic purification. This method was used to successfully deprotect a series of oligonucleotides at the 1, 100, and 150 mumole scales. These deprotection results were compared to a commonly used two step method and found to be superior in yield of product by as much as 250%. PMID- 8502545 TI - Excision of 3-methylguanine from alkylated DNA by 3-methyladenine DNA glycosylase I of Escherichia coli. AB - Escherichia coli has two DNA glycosylases for repair of DNA damage caused by simple alkylating agents. The inducible AlkA DNA glycosylase (3-methyladenine [m3A] DNA glycosylase II) removes several different alkylated bases including m3A and 3-methylguanine (m3G) from DNA, whereas the constitutively expressed Tag enzyme (m3A DNA glycosylase I) has appeared to be specific for excision of m3A. In this communication we have reexamined the substrate specificity of Tag by using synthetic DNA rich in GC base pairs to facilitate detection of any possible methyl-G removal. In such DNA alkylated with [3H]dimethyl sulphate, we found that m3G was excised from double-stranded DNA by both glycosylases, although more efficiently by AlkA than by Tag. This was further confirmed using both N [3H]methyl-N-nitrosourea- and [3H]dimethyl sulphate-treated native DNA, from which Tag excised m3G with an efficiency that was about 70 times lower than for AlkA. These results can explain the previous observation that high levels of Tag expression will suppress the alkylation sensitivity of alkA mutant cells, further implying that m3G is formed in quantity sufficient to represent an important cytotoxic lesion if left unrepaired in cells exposed to alkylating agents. PMID- 8502546 TI - The nucleolar transcription activator UBF relieves Ku antigen-mediated repression of mouse ribosomal gene transcription. AB - Previously we have shown that the RNA polymerase I (Pol I)-specific transcription factor UBF stimulates transcription by both facilitating transcription complex formation and by relieving repression exerted by a negative-acting factor which competes for binding of the murine factor TIF-IB to the ribosomal gene promoter (1). We have purified and functionally characterized this repressor protein from Ehrlich ascites cells. The final preparation contained two polypeptides with molecular masses of 75 and 90 kDa, respectively. Both polypeptides interact with the rDNA promoter as revealed by UV-crosslinking experiments. The specificity of binding to the ribosomal gene promoter was demonstrated in an electrophoretic mobility shift assay and by DNase footprinting. The biochemical properties of this negative-acting factor closely resemble those of the Ku antigen, a human nuclear DNA-binding heterodimer which is the target of autoantibodies in several autoimmune diseases. Anti-Ku antibodies precipitate the repressor activity and overcome transcription inhibition. The data demonstrate that regulation of Pol I gene transcription may involve an antirepression mechanism as already documented for Pol II genes and suggest that Ku protein may be causally involved in repressor-mediated down regulation of rRNA synthesis. PMID- 8502548 TI - The DNA binding specificity of the basic region of the yeast transcriptional activator GCN4 can be changed by substitution of a single amino acid. AB - The X-ray structure of a GCN4 DNA complex (1) shows, that specific DNA binding of the GCN4 basic region is mediated by a complicated network of base pair and DNA backbone contacts. According to the X-ray structure, alanine -14 of the basic region of GCN4 (we define the first leucine of the leucine zipper as +1) makes a hydrophobic contact to the methyl group of the thymine next to the center of the GCN4 binding site 5' ATGACTCAT 3'. We tested the DNA binding properties of the nineteen derivatives of GCN4, which carry all possible amino acids in position 14 of the basic region. Substitution of alanine -14 of GCN4 by either asparagine or cysteine changes the DNA binding specificity. Serine in this position broadens the specificity for position 1 of the target, whereas other amino acids either retain or decrease GCN4 specificity. PMID- 8502547 TI - Far upstream regions of class II MHC Ea are necessary for position-independent, copy-dependent expression of Ea transgene. AB - The chromatin upstream of the class II MHC Ea gene contains specific, DNase I hypersensitive (DH) sites (groups I-V), overlapping and extending the promoter proximal and distal control regions. To determine whether the Ea DH groups I-V define a functionally important chromatin domain or locus control region (LCR), we have used wild type Ead gene constructs to generate transgenic mouse lines from strains that do not express an endogenous Ea gene product. Constructs contained either DH groups I-V 'Longs' or DH groups I-II 'Shorts', of the hypersensitive sites defined within 20 kb 5' of Ea. We show that position independent, copy number-dependent expression of the Ead gene occurs only with the Long construct (8/8 transgenic mouse lines, over a range of copy numbers, 1 30 copies); in contrast, the Short constructs are subject to position-dependent effects. This suggests that the region delineated by Ea DH groups I-II is necessary but not sufficient as an LCR, which requires the presence of the upstream regions containing DH III-V for complete position-independent, copy number-dependent expression. These results introduce an immunologically important, putative LCR which can be used to target genes to cells of the B cell lineage, as well as to other class II MHC expressing cells, and highlight the importance of chromatin structure analysis as a means to locate DNA regions of regulatory interest which are dispersed over a large distance. PMID- 8502550 TI - Sequence selective double strand DNA cleavage by peptide nucleic acid (PNA) targeting using nuclease S1. AB - A novel method for sequence specific double strand DNA cleavage using PNA (peptide nucleic acid) targeting is described. Nuclease S1 digestion of double stranded DNA gives rise to double strand cleavage at an occupied PNA strand displacement binding site, and under optimized conditions complete cleavage can be obtained. The efficiency of this cleavage is more than 10 fold enhanced when a tandem PNA site is targeted, and additionally enhanced if this site is in trans rather than in cis orientation. Thus in effect, the PNA targeting makes the single strand specific nuclease S1 behave like a pseudo restriction endonuclease. PMID- 8502549 TI - Consensus sequences for good and poor removal of uracil from double stranded DNA by uracil-DNA glycosylase. AB - We have purified uracil DNA-glycosylase (UDG) from calf thymus 32,000-fold and studied its biochemical properties, including sequence specificity. The enzyme is apparently closely related to human UDG, since it was recognised by a polyclonal antibody directed towards human UDG. SDS-PAGE and western analysis indicate an apparent M(r) = 27,500. Bovine UDG has a 1.7-fold preference for single stranded over double stranded DNA as a substrate. Sequence specificity for uracil removal from dsDNA was examined for bovine and Escherichia coli UDG, using DNA containing less than one dUMP residue per 100 nucleotides and synthetic oligonucleotides containing one dUMP residue. Comparative studies involving about 40 uracil sites indicated similar specificities for both UDGs. We found more than a 10-fold difference in rates of uracil removal between different sequences. 5'-G/CUT-3' and 5'-G/CUG/C-3' were consensus sequences for poor repair whereas 5'-A/TUAA/T-3' was a consensus for good repair. Sequence specificity was verified in double stranded oligonucleotides, but not in single stranded ones, suggesting that the structure of the double stranded DNA helix has influence on sequence specificity. Rate of uracil removal appeared to be slightly faster from U:A base pairs as compared to U:G mis-matches. The results indicate that sequence specific repair may be a determinant to be considered in mutagenesis. PMID- 8502551 TI - Two regions of the Escherichia coli 16S ribosomal RNA are important for decoding stop signals in polypeptide chain termination. AB - Two regions of the 16S rRNA, helix 34, and the aminoacyl site component of the decoding site at the base of helix 44, have been implicated in decoding of translational stop signals during the termination of protein synthesis. Antibiotics specific for these regions have been tested to see how they discriminate the decoding of UAA, UAG, and UGA by the two polypeptide chain release factors (RF-1 and RF-2). Spectinomycin, which interacts with helix 34, stimulated RF-1 dependent binding to the ribosome and termination. It also stimulated UGA dependent RF-2 termination at micromolar concentrations but inhibited UGA dependent RF-2 binding at higher concentrations. Alterations at position C1192 of helix 34, known to confer spectinomycin resistance, reduced the binding of f[3H]Met-tRNA to the peptidyl-tRNA site. They also impaired termination in vitro, with both factors and all three stop codons, although the effect was greater with RF-2 mediated reactions. These alterations had previously been shown to inhibit EF-G mediated translocation. As perturbations in helix 34 effect both termination and elongation reactions, these results indicate that helix 34 is close to the decoding site on the bacterial ribosome. Several antibiotics, hygromycin, neomycin and tetracycline, specific for the aminoacyl site, were shown to inhibit the binding and function of both RFs in termination with all three stop codons in vitro. These studies indicate that decoding of all stop signals is likely to occur at a similar site on the ribosome to the decoding of sense codons, the aminoacyl site, and are consistent with a location for helix 34 near this site. PMID- 8502553 TI - Repression of bacteriophage promoters by DNA and RNA oligonucleotides. AB - We are interested in creating artificial gene repressors based on duplex DNA recognition by nucleic acids rather than polypeptides. An in vitro model system involving repression of bacteriophage T7 RNA polymerase initiation has been employed to demonstrate that certain DNA oligonucleotides can repress transcription by site-specific triple-helix formation at two kinds of homopurine operator sequences [Maher, L. J., III, (1992) Biochemistry 31, 7587-7594]. Recognition in the purine motif is based on antiparallel oligonucleotide binding (G.G.C and T.A.T triplets). Recognition in the pyrimidine motif is based on parallel oligonucleotide binding (C+.G.C and T.A.T base triplets). Using this system, we report that the concentration-dependence of repression by DNA oligonucleotides provides triple-helix inhibition constant (Ki) estimates of approximately 2 x 10(-7) M for both purine motif and pyrimidine motif DNA complexes. RNA oligonucleotides are shown to repress promoters overlapping pyrimidine motif operators (Ki = 6 x 10(-7) M), but not purine motif operators. Although competent to hybridize to complementary single strands, RNA oligonucleotides fail to bind the purine motif operator. Partial substitution of deoxyribose residues tends to rescue repressor activity by RNA oligonucleotides in the purine motif. These results suggest prospects for, and constraints on, natural and artificial RNA-based repressors. PMID- 8502552 TI - Identification of two novel mouse nuclear proteins that bind selectively to a methylated c-Myc recognizing sequence. AB - The c-Myc recognizes the sequence CACGTG (Blackwell, T. K., Kretzner, L., Blackwood, E.M., Eisenman, R. N., and Weintraub, H. (1990) Science 250, 1149 1151), and its binding is inhibited by methylation of the core CpG (Prendergast, G. C. and Ziff, E. B. (1991) Science 251, 186-189). We identified two novel nuclear proteins, MMBP-1 and MMBP-2, that bound specifically and under physiological salt condition to the c-Myc binding motif of which cytidine in the CpG sequence was methylated. MMBP-1 was about 42 kD and MMBP-2 was about 63 kD. MMBP-1 was found in specific cells, while MMBP-2 was found in all the cell lines tested, suggesting that MMBP-1 may modulate the role of MMBP-2 in tissue specific manner. We propose that the two proteins play a role in the regulation of c-Myc function through stabilizing or destabilizing the methylation state of the c-Myc binding motif. PMID- 8502554 TI - Timing of replication of beta satellite repeats of human chromosomes. AB - The beta satellite sequences of the human genome are a family of genetic elements consisting of 68-69 bp monomeric units repeated contiguously in long arrays up to 1 Mb in length. We have determined the timing of replication of beta satellite subgroups located in the heterochromatic portion of chromosome 9 and on the acrocentric chromosomes in regions both distal and proximal to the rDNA genes. We report that these dispersed subgroups of beta satellite sequences all replicate late during S phase of the cell cycle. PMID- 8502555 TI - A new method for specific cleavage of megabase-size chromosomal DNA by lambda terminase. AB - The development of methods for cleavage of DNA at specific site(s) that are widely spaced would facilitate physical mapping of large genomes. Several methods for rare and specific cleavage of chromosomal DNAs require a nearly complete methylation of a given type of restriction site except the one that is specifically protected. It is expected that as the target DNA increases in length, it will become less likely to achieve nearly complete methylation. The intron-encoded endonucleases may also provide a capability to cleave megabase sized DNA segments due to their very large recognition sequences. However, there are endogenous cleavage sites in the chromosomes of most organisms. We present here a new method to specifically cleave intact chromosomal DNA using lambda terminase. A plasmid containing two specific cleavage sites (cohesive-end sites) for lambda-terminase was specifically introduced into the E.coli genome and into chromosome V of S.cerevisiae. Chromosomal DNA was prepared from the resulting strains, and then cleaved with lambda-terminase. The results showed that the 4.7 megabase pair (Mb) circular E.coli chromosome and the 0.58-Mb linear yeast chromosome V were specifically cleaved at the desired sites with very high efficiencies. The approach of using the lambda-terminase cleavage reaction is a simple one-step procedure with a high specificity which is particularly suitable for mapping very large genomes of eucaryotes. PMID- 8502556 TI - The SpGAR1 gene of Schizosaccharomyces pombe encodes the functional homologue of the snoRNP protein GAR1 of Saccharomyces cerevisiae. AB - GAR1 is a nucleolar protein which is associated with small nucleolar RNAs (snoRNAs) and which is required for pre-ribosomal RNA processing. In Saccharomyces cerevisiae, the GAR1 gene is essential for cell viability. We have cloned and sequenced the GAR1 gene from the distantly related yeast Schizosaccharomyces pombe. The SpGAR1 gene, which contains two small introns, codes for a 194 amino-acid protein of 20 kDa. A protein sequence comparison indicates that SpGAR1 is 65% identical to ScGAR1. Anti-ScGAR1 antibodies recognize SpGAR1, emphasizing the structural conservation of the protein. Immunostaining of S.pombe cells with these antibodies reveals that SpGAR1 is localized in the nucleolus, as is the case in S.cerevisiae. Moreover, SpGAR1 can substitute for GAR1 in S.cerevisiae, indicating that the two proteins are functionally equivalent. These results suggest a parallel evolutionary conservation of proteins and RNAs with which GAR1 interacts in mediating its pre rRNA processing and viability functions. After fibrillarin, GAR1 is the second protein of the snoRNPs shown to have been conserved throughout evolution. PMID- 8502557 TI - GAL4-I kappa B alpha and GAL4-I kappa B gamma activate transcription by different mechanisms. AB - I kappa B proteins regulate Rel/NF-kappa B transcription complexes through a direct protein-protein interaction. In addition, we have previously shown that certain I kappa B proteins (I kappa B alpha and I kappa B gamma) can act as activators of transcription when fused to the DNA-binding domain of GAL4. We now show that a mutant chicken I kappa B alpha protein that cannot interact with Rel proteins in vitro did not activate transcription when fused to GAL4 in chicken embryo fibroblasts (CEF) and Saccharomyces cerevisiae, and did not inhibit growth in yeast; in contrast, an I kappa B alpha mutant that can still interact in vitro with Rel proteins activated transcription in both CEF and yeast and inhibited growth in yeast. In CEF, GAL4-I kappa B alpha mediated transcription activation was inhibited by co-transfection with an expression vector for a RelA (p65) protein that contained sequences needed for interaction with I kappa B alpha but that was deleted of its transcription activation domain. Therefore, it appears that GAL4-I kappa B alpha activates transcription by interacting with an endogenous Rel family protein in CEF. In contrast, the activation domain from I kappa B gamma behaved as a genuine acidic activator of transcription and did not inhibit growth when expressed in yeast. Since transcription activation and growth inhibition by GAL4-I kappa B alpha mutants in yeast correlated with their ability to interact with vertebrate Rel proteins, our results suggest that these activities of GAL4-I kappa B alpha are mediated through interaction with a Rel like protein in yeast, which is important for cell growth. PMID- 8502558 TI - Structural requirements for efficient translational frameshifting in the synthesis of the putative viral RNA-dependent RNA polymerase of potato leafroll virus. AB - The putative RNA-dependent RNA polymerase of potato leafroll luteovirus (PLRV) is expressed by -1 ribosomal frameshifting in the region where the open reading frames (ORF) of proteins 2a and 2b overlap. The signal responsible for efficient frameshift is composed of the slippery site UUUAAAU followed by a sequence that has the potential to adopt two alternative folding patterns, either a structure involving a pseudoknot, or a simple stem-loop structure. To investigate the structure requirements for efficient frameshifting, mutants in the stem-loop or in the potential pseudoknot regions of a Polish isolate of PLRV (PLRV-P) have been analyzed. Mutations that are located in the second stem (S2) of the potential pseudoknot structure, but are located in unpaired regions of the alternative stem-loop structure, reduce frameshift efficiency. Deletion of the 3' end sequence of the alternative stem-loop structure does not reduce frameshift efficiency. Our results confirm that -1 frameshift in the overlap region depends on the slippery site and on the downstream positioned sequence, and propose that in PLRV-P a pseudoknot is required for efficient frameshifting. These results are in agreement with those recently published for the closely related beet western yellows luteovirus (BWYV). PMID- 8502559 TI - Variant mapping of the Apo(B) AT rich minisatellite. Dependence on nucleotide sequence of the copy number variations. Instability of the non-canonical alleles. AB - Because of its variations in length, the AT rich Hyper-Variable Region (HVR) of the 3' end of the Apolipoprotein B gene is used as a polymorphic maker in genetic studies. It contains a SspI site in its repeated motif and we used this feature to precisely analyse the internal structure of the different alleles found at this locus in a Caucasian population. We performed total digestion on 194 alleles as well as Minisatellite Variant Repeat mapping (MVR mapping: partial digestion) on 54. The results show that the level of length variability (in copy number) of the 5' end of this locus is at least two times higher than that of the 3' end. This could be correlated with the difference in nucleotide sequence between the two parts of the HVR and suggests the dependence on the primary structure of the mechanism that produces length variability. A molecular model is proposed to explain this result. Moreover, the sharp analysis of the minisatellite structure by the distribution of SspI sites reveals differences between long and short alleles, indicating that in most cases, no recombination occurs between alleles of different sizes. Finally the rare alleles exhibit a non-canonical structure. These important points could explain the bimodal distribution of the frequencies of the alleles in the population. PMID- 8502560 TI - Negative regulatory elements upstream of a novel exon of the neuronal nicotinic acetylcholine receptor alpha 2 subunit gene. AB - The expression of the nicotinic acetylcholine receptor alpha 2 subunit gene is highly restricted to the Spiriform lateralis nucleus of the Chick diencephalon. As a first step toward understanding the molecular mechanism underlying this regulation, we have investigated the structural and regulatory properties of the 5' sequence of this gene. A strategy based on the ligation of an oligonucleotide to the first strand of the cDNA (SLIC) followed by PCR amplification was used. A new exon was found approximately 3kb upstream from the first coding exon, and multiple transcription start sites of the gene were mapped. Analysis of the flanking region shows many consensus sequences for the binding of nuclear proteins, suggesting that the 1 kb flanking region contains at least a portion of the promoter of the gene. We have analysed the negative regulatory elements present within this region and found that a silencer region located between nucleotide -144 and +76 is active in fibroblasts as well as in neurons. This silencer is composed of six tandem repeat Oct-like motifs (CCCCATGCAAT), but does not bind any member of the Oct family. Moreover these motifs were found to act as a silencer only when they were tandemly repeated. When two, four or five motifs were deleted, the silencer activity of the motifs unexpectedly became an enhancer activity in all cells we have tested. PMID- 8502561 TI - Unusually biased nucleotide sequences on sense strands of Flavobacterium sp. genes produce nonstop frames on the corresponding antisense strands. AB - From investigation of eight Flavobacterium sp. genes encoding enzyme proteins, it was found that six genes had nonstop frames (NSFs) on the antisense strands, and base sequences of the genes are mainly composed of repeating triplet sequence(s), 5'-GNC-3' (where G and C are guanine and cytosine, and N is either of the four bases), in the reading frames. Thus, we concluded that the biased nucleotide sequences on the sense strands produce NSFs on the corresponding antisense strands. Furthermore, from the precise alignments of both nucleotide and amino acid sequences of two related Flavobacterium sp. genes, nyIB and nyIB', it was found that base replacements might have occurred symmetrically in the codons. That is, transversions between G and C were observed at high frequencies at the first and third positions of codons, but not at the second positions. At the first position, AG base transitions were observed much more than similar CT transitions, whereas CT transitions were found at the third positions at a relatively high frequency. These suggest that symmetrical base replacements in codons might be the main contribution to evolution in Flavobacterium sp. genes. PMID- 8502562 TI - Crystal structure of a Z-DNA hexamer d(CGCICG) at 1.7 A resolution: inosine.cytidine base-pairing, and comparison with other Z-DNA structures. AB - The crystal structure of the deoxyhexamer, d(CGCICG), has been determined and refined to a resolution of 1.7A. The DNA hexamer crystallises in space group P2(1)2(1)2(1) with unit cell dimensions of a = 18.412 +/- .017 A, b = 30.485 +/- .036A, and c = 43.318 +/- .024 A. The structure has been solved by rotation and translation searches and refined to an R-factor of 0.148 using 2678 unique reflections greater than 1.0 sigma (F) between 10.0-1.7 A resolution. Although the crystal parameters are similar to several previously reported Z-DNA hexamers, this inosine containing Z-DNA differs in the relative orientation, position, and crystal packing interactions compared to d(CGCGCG) DNA. Many of these differences in the inosine form of Z-DNA can be explained by crystal packing interactions, which are responsible for distortions of the duplex at different locations. The most noteworthy features of the inosine form of Z-DNA as a result of such distortions are: (1) sugar puckers for the inosines are of C4'-exo type, (2) all phosphates have the Zl conformation, and (3) narrower minor grove and compression along the helical axis compared to d(CGCGCG) DNA. In addition, the substitution of guanosine by inosine appears to have resulted in Watson-Crick type base pairing between inosine and cytidine with a potential bifurcated hydrogen bond between inosine N1 and cytidine N3 (2.9 A) and O2 (3.3-3.A). PMID- 8502563 TI - Definition of a new alpha satellite suprachromosomal family characterized by monomeric organization. AB - We have analyzed more than 500 alphoid monomers either sequenced in our laboratory or available in the literature. Most of them belonged to the well studied suprachromosomal families 1, 2 and 3 characterized by dimeric (1 and 2) and pentameric (3) ancestral periodicities. The sequences that did not belong to the previously known families were subjected to further analysis. About a half of them formed a relatively homogenous family. Its members were on average 80.5% identical and 89.5% homologous to the M1 consensus sequence derived from this group (39 monomers). In the genome they do not form any ancestral periodicities other than a monomeric one, and are found at least in chromosomes 13, 14, 15, 21, 22 and Y. The newly defined family was termed suprachromosomal family 4. Comparison of all 10 alphoid monomeric groups identified so far showed that the M1 sequence is closely related to the J1-D2-W4-W5 homology grouping. Notably the African Green Monkey alpha satellite, also characterized by monomeric construction, appears to be a member of the same group. PMID- 8502564 TI - Genomic sequences capable of committing mouse and rat fibroblasts to adipogenesis. AB - The mouse Swiss 3T3-F442A/3T3-C2 cell system is well suited for the isolation of genes involved in commitment to adipogenesis. 3T3-F442A cells convert to adipocytes with high efficiency in response to confluence and insulin. The sister clonal line 3T3-C2 does not respond to these signals, but can convert to adipocytes when transfected with DNA from 3T3-F442A preadipocytes or from human fat. Human fat-tissue biopsy FO46 DNA transfected into 3T3-C2 gave rise to fat foci after two rounds of transfection and selection. A cosmid library of a subclone of secondary transfectant 3T3-C2/FO46-1 was screened for the human repetitive Alu sequence. Five out of eight Alu+ recombinant clones committed 3T3 C2 cells to adipogenesis. The adipose commitment (AC) activity of one cosmid, p18A4, was found to reside in two small, non-identical, subcloned sequences 1.2kb and 2.0kb in length, each separately able to commit 3T3-C2, precrisis mouse and rat fibroblasts and the multipotential C3H10T1/2 cell line to adipogenesis. We conclude that commitment to adipogenesis can be effected in vitro with high efficiency by transfection of specific sequences into a variety of host cells. PMID- 8502565 TI - The Rb97D gene encodes a potential RNA-binding protein required for spermatogenesis in Drosophila. AB - Many proteins that bind RNA contain a common RNA-binding domain, the RNP motif. We have been studying two Drosophila RNP motif proteins, Hrb98DE and Hrb87F, which are hnRNA-binding proteins. We report here the characterization of the Rb97D gene, which encodes a protein that is closely related to the Hrb proteins in the RNP motif domain, but has a distinctive proline-rich C-terminal domain. The gene is located at 97D on the right arm of the third chromosome, near the rough gene. Multiple transcripts from the Rb97D gene are present at varying levels throughout development. The transcripts are generated by alternative processing in the coding and 3' untranslated regions, and can encode two protein isoforms. Analysis of a mutant containing a P element inserted into the 5' untranslated region of the gene demonstrates that Rb97D is required for male fertility. Possible models for the function of Rb97D in testes are discussed. PMID- 8502566 TI - Accelerated poly(A) loss and mRNA stabilization are independent effects of protein synthesis inhibition on alpha-tubulin mRNA in Chlamydomonas. AB - In Chlamydomonas, the usual rapid degradation of tubulin mRNAs induced by flagellar amputation is prevented by inhibition of protein synthesis with cycloheximide. Evidence is presented that the ability of cycloheximide to stabilize alpha-tubulin mRNA depends on the time of addition. Addition of cycloheximide to cells before induction strongly stabilizes the induced mRNAs, while addition after their synthesis stabilizes them only transiently. Moreover, cycloheximide inhibition does not stabilize the same alpha-tubulin mRNA species in uninduced cells. These results suggest that cycloheximide is not acting to stabilize the induced alpha-tubulin mRNAs simply by preventing ribosome translocation. The stabilized state of tubulin mRNA was found to correlate with its occurrence on smaller polysomes but larger EDTA-released mRNP particles than the unstable state. A second effect of cycloheximide on the metabolism of induced tubulin mRNAs is to accelerate complete poly(A) removal. This effect of cycloheximide inhibition, unlike stabilization, occurs whenever cycloheximide is added to cells, and appears unrelated to stabilization. The effect is shown to be mRNA-specific; poly(A)-shortening on the rbcS2 mRNA is not altered in the presence of cycloheximide, nor do completely deadenylated molecules accumulate. Experiments in which cells were released from cycloheximide inhibition suggest that deadenylated alpha-tubulin mRNAs may be less stable than their polyadenylated counterparts during active translation. PMID- 8502567 TI - The nucleosome repeat length of Kluyveromyces lactis is 16 bp longer than that of Saccharomyces cerevisiae. PMID- 8502568 TI - 16S rDNA sequence analysis of Acholeplasma seiffertii, a mollicute from plant surfaces, and its transfer to mesoplasma, a new genus in the spiroplasma phylogenetic group. PMID- 8502569 TI - Putative tfIIs gene of Sulfolobus acidocaldarius encoding an archaeal transcription elongation factor is situated directly downstream of the gene for a small subunit of DNA-dependent RNA polymerase. PMID- 8502570 TI - A new subfamily of recently retroposed human Alu repeats. PMID- 8502571 TI - Nucleotide sequence of U1 RNA from a green alga, Chlamydomonas reinhardtii. PMID- 8502572 TI - Sequence of the Providencia rettgeri lexA gene and its control region. PMID- 8502573 TI - Complete nucleotide sequence of the non-structural gene of the human influenza virus strain A/WS/33. PMID- 8502574 TI - Complete nucleotide sequence of a hepatitis B virus, subtype adw2, and identification of three types of C open reading frame. PMID- 8502575 TI - Correction of the nucleotide and amino acid sequence of Xenopus laevis 42Sp50. PMID- 8502576 TI - A simple and rapid method for the preparation of gram-negative bacterial genomic DNA. PMID- 8502577 TI - A simple method for identification of point mutations using denaturing gradient gel electrophoresis. PMID- 8502578 TI - Direct sequencing of single primer PCR products: a rapid method to achieve short chromosomal walks. PMID- 8502580 TI - Exon-enriched probe derived from a human chromosome 21 YAC by exon-amplification. PMID- 8502579 TI - Combinatorial infection and in vivo recombination: a strategy for making large phage antibody repertoires. PMID- 8502581 TI - A method to increase the cumulative cleavage efficiency of ribozymes: thermal cycling. PMID- 8502582 TI - An efficient 1-tube PCR method for internal site-directed mutagenesis of large amplified molecules. PMID- 8502583 TI - Polyethylene tube: an alternative support for synthesis and purification of biotin-labeled single-stranded DNA probes. PMID- 8502584 TI - Prevention of photocarcinogenesis by dietary vitamin E. AB - Ultraviolet B (UV-B) irradiation of C3H/HeN mice induces skin cancer. In this study, the ability of dietary d-alpha-tocopheryl acetate to reduce photocarcinogenesis was tested in this murine model. Skin cancers developed in 67.5% of UV-B-irradiated mice by 31 weeks after the first UV exposure. Supplementation with 100 or 200 IU of d-alpha-tocopheryl acetate per kilogram of diet led to a reduction of the incidence to 46% and 19%, respectively. The latter value was significantly different from that found in mice fed the basal diet (p = 0.039, one-sided P value by log-rank test). Skin levels of alpha-tocopherol varied with the dietary dose of d-alpha-tocopheryl acetate. No toxicity was evident in unirradiated mice fed the vitamin E-supplemented diet, but 40% of the UV-B-irradiated mice fed 200 IU of vitamin E per kilogram of diet died by 31 weeks after the first UV-B treatment. Decreased relative spleen weight was observed in the UV-B-irradiated mice fed the vitamin E-supplemented diet. In summary, oral d-alpha-tocopheryl acetate prevented photocarcinogenesis, but at doses that were toxic to inbred C3H/HeN mice after exposure to 8.6 x 10(5) J/m2 of UV-B irradiation. PMID- 8502585 TI - Omega-3 fatty acid modification of membrane structure and function. II. Alteration by docosahexaenoic acid of tumor cell sensitivity to immune cytolysis. AB - Docosahexaenoic acid (DHA, 22:6) is a long-chain omega-3 fatty acid abundant in cold water fish; it is the most unsaturated fatty acid found in biologic systems and is reported to alter membrane structure. To explore DHA's effect on membrane function, we have fused tumor cells with synthetic phosphatidylcholine (PC) containing stearic acid in the sn-1 position and DHA in the sn-2 position (18:0, 22:6 PC) and have found the lipid-modified tumor cells to be more sensitive to cytolysis by alloreactive cytotoxic T lymphocytes. Cold target competition experiments suggested that fusion of tumor plasma membranes with 18:0, 22:6 PC produced a qualitative change in expression of surface antigens recognized by cytotoxic T lymphocytes. We monitored the expression of various epitopes on tumor cells by complement-mediated lysis and radioimmunoassay with monoclonal antibodies against H-2 class I antigens. Our results suggest that membrane-bound DHA increases the expression of some epitopes while decreasing the expression of others and that different tumor lines vary in the magnitude of DHA's effect. Our findings are consistent with a model in which DHA-containing phospholipids segregate into membrane domains, in turn altering the expression of membrane proteins. PMID- 8502586 TI - The interrelationship of weight loss, dietary intake, and quality of life in ambulatory patients with cancer of the lung, breast, and ovary. AB - One hundred four consecutive patients with newly diagnosed small cell lung cancer, metastatic breast cancer, and ovarian cancer in good physical functional condition (performance rating 0-1 on Eastern Cooperative Oncology Group scale) were divided into a weight-losing group (> or = 5% unintentional weight loss within 3 mo; n = 48) and a weight-stable group (n = 56). Dietary intakes in relation to fat-free mass were not different in the two groups. According to the Quality of Life index and the General Health Questionnaire, weight-losing patients had significantly lower quality of life than weight-stable patients. In patients with weight loss, daily intakes of energy and protein correlated significantly with scores on the General Health Questionnaire. This study has shown that many ambulatory cancer patients do not eat enough to maintain weight and that even a moderate weight loss is associated with psychological distress and lower quality of life. PMID- 8502587 TI - Consumption of meat and fruit in relation to oral and esophageal cancer: a cross national study. AB - Using data from 59 countries, we conducted an international comparison study to identify nutritional predictors of age-adjusted oral and esophageal cancer mortality rates. Statistical models accounted for per capita tobacco disappearance data, alcohol consumption, and various measures of socioeconomic status. For oral cancer, stepwise regression results showed protective effects for milk/dairy products (B = -0.030, p < 0.0001) and cabbage consumption (B = 0.391, p = 0.01) and increased risk from vegetable oil (B = 0.072, p = 0.04) and excess animal fat calories (B = 0.344, p < 0.0001) as well as marginally increased risk from cereals (B = 0.008, p = 0.08). Results were obtained after accounting for all background factors, including sex (model R2 = 0.52). For esophageal cancer, stepwise results indicated protective effects for fruit (B = 0.046, p = 0.0006) and total caloric intake (B = -0.013, p < 0.0001) and increased risk from vegetable oil (B = 0.061, p = 0.04) and meat (B = 0.031, p < 0.0001) consumption (model R2 = 0.55). When analyzed separately by sex, results were similar, indicating that the risk factors are probably the same in both sexes, even though women consistently have fewer deaths, on average, from these cancers. On the basis of results from stepwise regression models, we also fitted general linear models for mortality rates of each cancer site, and results were similar in terms of magnitude and direction of effects. Although the evidence provided by this type of analysis using data aggregated by country is limited in terms of control for potential confounding effects and modeling of possible effect modification, an effect of high meat, animal product, or vegetable oil and low fruit and cabbage consumption is consistent with the known biology of these tumors. PMID- 8502588 TI - Alteration of membrane fatty acid composition and inositol phosphate metabolism in HT-29 human colon cancer cells. AB - The present study was designed to investigate the role of membrane fatty acid (FA) composition on inositol phosphate (InsP) release by a human colon tumor cell line. Cells were supplemented for five days in culture with 0, 10, 30, or 100 microM sodium stearate (18:0), linoleate [18:2(omega-6)], or linolineate [18:3(omega-3)]. These FAs were supplied as a complex with FA-free bovine serum albumin. InsP release was examined in these cells with or without stimulation with deoxycholic acid (DCA) after they were labeled with [3H]myoinositol. FA enrichment was found to influence inositol incorporation into membrane lipids. Although 18:0 had no effect, 18:2(omega-6) decreased the incorporation. On the other hand, 18:3(omega-3) increased the incorporation of inositol compared with the cells supplemented with the other FAs, but they were not different from control. Basal release of total InsP was elevated only with supplementation of 10 and 30 microM 18:3(omega-3). FA supplementation with 18:0 at 30 microM and 18:2 at 30 and 100 microM resulted in downregulation of bsal release of InsP. Enrichment of HT-29 cell membranes with polyunsaturated FAs resulted in a significant increase in stimulated release of InsP, but this was not seen with saturated FA supplementation. At 10 microM supplementation, 18:2 had the greatest effect on stimulated InsP release. This effect of 18:2 disappeared at 30 microM. However, the increase in the stimulated InsP release caused by 18:3 occurred at 10 and 30 microM. DCA-stimulated release of InsP was not downregulated by any FA supplementation. This study showed that enrichment of the membranes with polyunsaturated FAs increases the response of the phosphatidylinositol cycle to DCA stimulation. In addition, enrichment with 18:3(omega-3) increases the basal turnover of InsP. It is concluded that alteration of membrane FAs has a profound effect on the phosphatidylinositol cycle. PMID- 8502589 TI - Effects of various preparations of dietary protease inhibitors on oral carcinogenesis in hamsters induced by DMBA. AB - We studied the ability of a soybean extract containing the Bowman-Birk protease inhibitor (BBI), referred to as BBI concentrate (BBIC), purified BBI (PBBI), and the chymotrypsin inhibitor from potatoes to suppress oral carcinogenesis in hamsters induced by 7,12-dimethyl-benz[a]anthracene (DMBA). Application of 1% solutions of BBIC and PBBI five times per week to DMBA-treated hamster cheek pouches were highly effective in suppressing oral carcinogenesis, whereas a 1% solution of the chymotrypsin inhibitor from potatoes did not lead to a significant suppression of carcinogenesis. BBIC and PBBI suppressed carcinogenesis at concentrations ranging from 1% to 0.01% and were equally effective when given as a 1% solution five times per week, three times per week, or once per week. A 1% solution of BBIC suppressed oral carcinogenesis when given at the following times during the assay period: 0-180, 0-90, 14-90, and 45-135 days. Thus, protease inhibitor treatment could be started as late as 45 days after the beginning of the carcinogen exposure and have an irreversible suppressive effect on the carcinogenic process. PMID- 8502590 TI - Increased levels of luminol-enhanced chemiluminescence by rectal mucosa of patients with colonic neoplasia: a possible marker for colonic neoplasia. AB - Increased colonic cell proliferation (CCP) has been reported in patients with colonic neoplasia. Previous studies in rats suggest that increased CCP is closely related to increased reactive oxygen metabolite (ROM) production. We hypothesized that, in humans, ROM production is also involved in increased CCP. Using a chemiluminescence probe, we estimated the levels of ROMs in the rectal mucosa of 37 patients who previously had colonic neoplasia (14 with cancer and 23 with polyps) and 20 control subjects who had normal colonoscopic examination and no history of colonic neoplasia. Normal-appearing rectal mucosa of patients with colonic neoplasia contained significantly higher levels of luminol-enhanced chemiluminescence (LECL) than rectal mucosa of control subjects (p < 0.01). There was no difference in LECL levels between patients with polyps and patients with cancer. Four of 20 controls and 31 of 37 patients had LECL levels 1,000 cpm/mg protein (positive and negative predictive values of 89% and 73%, respectively). Addition of indomethacin, a specific cyclooxygenase inhibitor, to the tissue suspension significantly decreased LECL levels. These preliminary data suggest that 1) ROMs may be involved in both the rate of CCP and the process of malignant cellular transformation, 2) oxidation of arachidonic acid via the cyclooxygenase pathway significantly contributes to the production of ROMs in rectal mucosa, and 3) measurement of the levels of LECL produced by the rectal mucosa may be a sensitive marker to screen for colonic neoplasia. PMID- 8502591 TI - Beta-carotene decreases markers of lipid peroxidation in healthy volunteers. AB - We previously showed that daily intake of beta-carotene, a nontoxic antioxidant, reduces lipid peroxidation as assessed by serum lipid peroxide levels. An alternative method to detect lipid peroxidation is the measurement of pentane in breath. Pentane is a five-carbon hydrocarbon that is released when an omega-6 unsaturated fatty acid undergoes peroxidation. The aim of this study was to see whether graded doses of beta-carotene would affect breath pentane excretion in normal subjects placed on a carotenoid-free liquid diet for two weeks. The subjects were then repleted with either 15 (n = 7) or 120 mg (n = 8) of beta carotene daily for four weeks while continuing the same diet. Serum beta-carotene and breath pentane were measured before and after beta-carotene refeeding. Lipid peroxidation, as assessed by gas-chromatographic measurement of breath pentane, was significantly (p < 0.05) reduced by daily supplements of 120 mg beta-carotene (from 3.7 +/- 0.9 to 2.2 +/- 1.4 nmol/l). However, the decline in pentane exhalation observed with the 15-mg beta-carotene dose did not achieve statistical significance (p = 0.13). PMID- 8502592 TI - [Test with calcitonin as an index of parathyroid function in chronic renal failure]. AB - The aim of this study was to evaluate the clinical usefulness of the calcitonin test in predicting the hyperparathyroid bone disease severity in uremia. 200 IU of synthetic salmon calcitonin was given intranasally to 77 hemodialysed patients with end-stage renal failure. Before the test, serum calcium, PTH and serum alkaline phosphatase had been sampled; serum calcium was determined also in 2 to 4 hours after. The subjects were divided into 3 groups according to their serum PTH levels. Group I consisted of 24 patients with at least 10-fold serum PTH elevation, group II of 34 patients with intermediate values, and group III of 19 patients with serum PTH within normal range. In the group I the mean serum calcium fall was 0.32 +/- 0.16 mmol/l (1.28 +/- 0.64 mg/dl) (p < 0.001) and 0.27 +/- 0.15 mmol/l (1.08 +/- 0.60 mg/dl) (p < 0.001), after 2 to 4 hours respectively. In the group II serum calcium decreased by 0.16 +/- 0.12 mmol/l (0.64 +/- 0.48 mg/dl) after 2 hours and by 0.14 +/- 0.09 mmol/l (0.56 +/- 0.36 mg/dl) after 4 hours; the differences were statistically insignificant. In the group III no reduction in serum calcium was observed. In the whole 77 patients population significant linear correlations between the hypocalcemic response and iPTH as well as serum alkaline phosphatase were found. Our results confirm that the calcitonin-induced hypocalcemia a test can be, in addition to serum alkaline phosphatase and PTH evaluation, a simple and useful index of advanced hyperparathyroid bone disease in hemodialysed patients with chronic renal failure. PMID- 8502593 TI - [The effect of long-term prazosin treatment on plasma follitropin (FSH), lutropin (LH), prolactin, estradiol and testosterone concentration in male patients with essential hypertension]. AB - The influence of prazosin treatment for 12 months on basal and LH-RH stimulated FSH, LH, estradiol and testosterone secretion and basal and chlorpromazine stimulated prolactin secretion was estimated in 15 male patients with essential hypertension. Male hypertensive patients were characterized by significantly elevated FSH and reduced testosterone secretion as compared with controls. In contrast, plasma LH, prolactin and estradiol concentrations were similar in both examined groups. After 12 months of prazosin treatment basal and stimulated LH and prolactin secretion significantly decreased while estradiol secretion significantly increased. Prazosin treatment for 12 months did not influence significantly LH and testosterone secretion. CONCLUSIONS: 1. Data presented in this study suggest the presence of abnormal function of the pituitary--gonadal axis in male patients with essential hypertension. 2. Long-term prazosin treatment shows an inhibitory effect on FSH and prolactin secretion but stimulatory one on estrogens secretion in male hypertensive patients. PMID- 8502594 TI - [Metabolic disorders in android obesity]. PMID- 8502595 TI - [Disorders of uric acid tubular transport leading to hypouricemia]. PMID- 8502596 TI - [Evolution of cutaneous changes observed in cirrhosis patients before and after liver transplantation]. AB - In 11 patients with liver cirrhosis a prospective study concerning the evolution of skin changes before and after liver transplantation was performed. Etiology of the disease was: alcoholic in 5 cases, post-inflammatory in 4 cases and primary biliary cirrhosis in 2. Evolution of: nevi spiders, erythema palmar, changes in nails, Hippocrates fingers, discoloration of legs, bilateral Dupuytren's disease and gynecomastia (in man) were estimated. At the same time sex hormones levels were measured. One month after liver transplantation a reduction of total spiders number as well as the frequency of the erythema palmare and nails changes was observed. During the next few months we observed disappearance of the legs discoloration and signs of gynecomastia and Hippocrates fingers. Only the Dupuytren's contractures remained unchanged. There was no correlation between sex hormones levels and skin changes except decrease of the total testosterone level (p < 0.05) and an increase of free testosterone to total testosterone ratio (p < 0.02) in women and a decrease of estradiol level (p < 0.02) in women and a decrease of estradiol level (p < 0.002) in men after operation. CONCLUSION: skin changes typical for liver cirrhosis can be reversible after liver transplantation. PMID- 8502597 TI - [Technical complications of peritoneal dialysis due to catheter dysfunction]. AB - The authors analysed causes of Tenckhoff peritoneal catheter dysfunction in 17 patients treated with standard peritoneal dialysis during 23.8 +/- 8.7 months. In 8 cases any catheter dysfunction were observed. Exit-site infection/tunnel infection were observed in 5 cases. Catheter obstruction or one-way obstruction of catheters caused by peritonitis was observed in 6 patients and 1/3 of implanted catheters. 3 of these patients were transferred to hemodialysis. Non infective complications/caused mainly by catheter migration/was observed in 3 patients and 1/3 of implanted catheters. In all these cases peritoneal dialysis was stopped. Mean one-year catheter survival was 58.8%, and two-year survival was 17.6%. The authors described the technique of catheter implantation and catheter care after operation. PMID- 8502598 TI - [Thrombolytic treatment of Budd-Chiari syndrome with portal venous thrombosis]. AB - Own material of 7 patients is presented pathology: venous thrombosis involving both hepatic veins and portal system, resulting in severe impairment of liver function and portal circulation, leading up to a fatal end (if not treated). Neither surgical decompression nor liver transplantation is feasible from the technical point of view. Patients were treated with activators of fibrinolysis. In four cases the treatment was effective and resulted in recanalisation of the previously occluded veins. Early re-thrombosis was the reason of death in one case. One patient died 4 years later because of cerebral vascular thrombosis. Two others live over 5 years, symptom-free. The authors consider thrombolytic treatment as a life saving procedure in cases of hepatic and portal venous thrombosis. PMID- 8502599 TI - [Is it possible to transplant kidneys from donors whose death was caused by ethylene glycol intoxication?]. AB - This paper describes 4 patients with a kidney graft from ethylene glycol intoxicated cadaver donors. Our results suggest usefulness of such donors for transplantation. PMID- 8502600 TI - [Treatment of diabetes mellitus with transplantation of Langerhans islets]. PMID- 8502601 TI - [Chronic thromboembolic pulmonary hypertension--not fully recognized clinical entity]. PMID- 8502602 TI - [Oral pulsatile therapy with active vitamin D3 metabolites--an efficient method of parathyroid hormone synthesis suppression in uremic patients with severe hyperparathyroidism. A pilot study]. AB - Standard therapy with orally administered active metabolites of vitamin D3 often does not satisfactorily control the biochemical manifestations of secondary hyperparathyroidism in uremic patients. This may be due to inadequate serum concentrations of 1,25 (OH)2D3 achieved during the treatment. Eighteen patients on chronic hemodialysis (HD) with severe hyperparathyroidism were given high doses of calcitriol (1,25 (OH)2D3) or alphacalcidol (1 alpha-OH-D3) orally, in ten evenings preceding each HD session. The effect of the treatment on circulating parathyroid hormone (PTH), serum hydroxyproline, serum alkaline phosphatase and bone isoenzyme was examined in a pilot study during 5 weeks. Irrespective the preparation given the treatment caused 71.7 +/- 22.2% reduction of intact serum PTH concentration with only moderate rise of serum calcium. A decrease of serum hydroxyproline and activity of alkaline phosphatase with its bone fraction, the direct indexes of bone turnover reduction, was also observed. With ongoing calcium carbonate therapy (3-6 g/day) 5 episodes of mild, asymptomatic hypercalcemia was observed for the 108 times of the total number of examinations; in those cases the dose of alphacalcidol was reduced. Our observations indicate that intermittent administration of 1,25 (OH)2D3 as well as 1 alpha-OH-D3 in high oral doses effectively suppress PTH synthesis in uremic hyperparathyroidism already in a couple of weeks. The effect is similar to that obtained with intravenous administration of the vitamin D3 active metabolites. PMID- 8502603 TI - Metabolism of [14C]propionic acid in broiler chicks. AB - Broiler chicks were given 4 or 120 mumol propionic[1-14C] acid by gavage to determine its chemical fate and distribution of radiolabel among organs and tissues [foregut (crop, gizzard, and proventriculus), intestine (small and large), ceca, liver, and serum]. At 15 and 60 min postgavage, most of the extractable radiolabel remaining in the chicks was found in the foregut. Significantly higher percentages of the administered radiolabel were detected at 15 min in the serum and liver extracts of chicks given 120 mumol of propionic acid than in chicks given only 4 mumol. After 15 min, 41 and 30%, respectively, of the total radiolabel administered was accounted for in extracts of the digestive tract and tissues of chicks given 4 or 120 mumol of [14C]propionic acid. Only about 12% of the administered radiolabel was extracted from body compartments at 60 min postgavage from chicks given 4 mumol of propionic acid. Collection of respired [14C]CO2 during a 3-h postgavage period indicated that orally administered propionic acid is largely (about 75%) used as an energy source or is metabolized and assimilated into body components. The present studies indicate that little if any dietary propionic acid reaches the lower digestive tract and the ceca. PMID- 8502604 TI - Additive amelioration of tibial dyschondroplasia in broilers by supplemental calcium or feed deprivation. AB - Two experiments were conducted to determine the effects of mineral nutrition and early growth rate on tibial dyschondroplasia (TD) in broiler chickens. A corn soybean meal diet with .6% available P (aP) was fed from the day of hatching for 20 days. Experiment 1 had a 2 x 2 x 2 factorial arrangement of treatments with two dietary levels of Ca (1.1 or 1.8% of the diet), two levels of dietary Cl (.22 or .34%), and two feeding systems (ad libitum or deprived of feed for 8 h three times per week on Monday, Wednesday, and Friday beginning at 6 days of age). Experiment 2 was a 3 x 2 factorial arrangement with three levels of Ca (1.14, 1.50, or 1.80%) and two feeding systems (ad libitum or deprivation as in Experiment 1). Nineteen-day BW gain was not affected by treatments in the first experiment. Feed deprivation decreased gain in the second experiment, and gain was increased by the highest Ca level without affecting feed efficiency. Feed deprivation did not affect feed efficiency in either experiment. Dietary Cl level did not affect any variable studied. Supplemental Ca increased bone ash in the first experiment, but not in Experiment 2. Feed deprivation and increasing Ca levels decreased the incidence of TD and the amount of severe lesions. Increasing dietary Ca resulted in a greater accumulation of Ca into the epiphyseal growth plate cartilage. The results suggest that the dietary Ca:aP ratio required for bone integrity in starter chicks may be greater than 2.2:1. PMID- 8502605 TI - Effects of amino acid restriction during starter and grower periods on subsequent performance and incidence of leg disorders in male large white turkeys. AB - Male Nicholas Large White turkeys were fed diets formulated to meet a minimum of 100, 110, or 120% of NRC (1984) amino acid recommendations. There were three periods when 75% of recommended standards were fed: 0 to 3 wk, 0 to 6 wk, or 6 to 12 wk. A fourth (control) group was not restricted at any time. Four pens of 12 males were fed each amino acid by restriction combination. At 18 wk, leg scores were assigned to all birds and representative samples of birds processed for parts yield. All birds fed restricted diets had significantly lower BW at 18 wk than unrestricted controls but did not differ in feed utilization. Dietary amino acid levels significantly influenced BW and feed utilization, but there was no interaction with restriction times. There were no significant effects of amino acid levels or restriction times on incidence of leg disorders. Breast meat yields (quantity and percentage of carcass) were significantly influenced by both restriction time and amino acid levels. There seemed to be little if any compensatory gain following amino acid restriction in these studies. PMID- 8502606 TI - Estrogen receptor binding in the hen hypothalamus and pituitary during the ovulatory cycle. AB - The equilibrium dissociation constant (Kd) and the maximum binding capacity (Bmax) of estrogen receptor in soluble (cytosolic) and insoluble (nuclear) fractions in a hypotonic buffer solution of hypothalamus containing preoptic (HPOA) and median eminence (HMEA) areas and of anterior pituitary (AP) of laying and nonlaying hens were examined by Scatchard analysis of specific [3H]estradiol 17 beta ([3H]-E2) binding. The Kd of receptor in all of the tissues was different neither between soluble and insoluble fractions, nor between laying and nonlaying hens. The Bmax in laying hens was greater in the insoluble fraction and lower in the soluble fraction than that in nonlaying hens, but the total binding capacity (sum of Bmax in the soluble and insoluble fractions) was not different between laying and nonlaying hens. In laying hens, the specific [3H]-E2 binding in the insoluble fraction of HPOA was found to increase at 21 h before ovulation and again at 8 to 6 h before ovulation, and of HMEA and AP at 18 to 11 h before ovulation. No change in the specific [3H]-E2 binding in the insoluble and soluble fractions was found in any of the tissues of nonlaying hens during a 24-h period. The results suggest that in laying hens, estrogen may act on the hypothalamus and pituitary at restricted hours during the ovulatory cycle. PMID- 8502607 TI - Molecular aspects of the synthesis and deposition of hens' egg yolk with special reference to low density lipoprotein. AB - Avian egg yolk contains three main macromolecular constituents: 1) the yolk granules; insoluble particles consisting largely of lipovitellin and phosvitin. They are synthesized in response to hormones in the liver as a precursor protein, vitellogenin, which is soluble in blood. It passes through the oolemma by receptor-mediated endocytosis and is split up enzymically to give fragments that precipitate as granules in the yolk. 2) The livetins; essentially blood serum proteins. The mechanism for their transfer to yolk is not clear. 3) The yolk low density lipoprotein; the major part of yolk (60% of the dry weight). It is synthesized and assembled in the liver as a modified blood very low density lipoprotein, whose main apoprotein is apo B. As with vitellogenin, it enters yolk by endocytosis. Furthermore it is split enzymically to give most of the yolk lipoprotein apoproteins (apovitellenins III to VI). New evidence for the relationship between yolk apoproteins and apo B has been derived from a comparison of the N-terminal amino acid sequences of apovitellenin IV and apo B. PMID- 8502608 TI - Regulation of follicle differentiation by gonadotropins and growth factors. AB - The rate of ovulation is determined by, among other things, the availability of small follicles that can be recruited into the follicular hierarchy. A decrease in the rate of lay with, for instance, aging has been attributed to both an increase in the rate of atresia and a decrease in the number of small, growing follicles that provide the pool from which follicles are selected into the final growth phase (the preovulatory hierarchy). Among the most important endocrine, paracrine, and autocrine factors that mediate follicle growth and differentiation are the gonadotropins and growth factors. A better understanding of gonadotropin growth factor interactions that occur during follicle selection and differentiation should lead to the development of management practices or genetic manipulations (Mendelian or molecular) that will enhance the rate of lay at times during the production cycle when egg production is suboptimal. PMID- 8502609 TI - Fertilization and early embryonic development in poultry. AB - There are two major controllers of development in the early stages of bird embryos. These are: 1) gravity, probably acting through the distribution of yolk and its components, which lays down the initial plans for polarity that are later established firmly through the genes; and 2) the primitive streak, which controls the orderly ingression of the cells and imposes a pattern on the developing tissues. PMID- 8502610 TI - Chimeric chickens and their use in manipulation of the chicken genome. AB - Germline chimeric chickens can be made by injecting dispersed cells from Stage X blastoderms into recipient embryos at an equivalent stage of development. Colonization of the chimera by donor-derived cells is facilitated when the recipient embryo is compromised by exposure to irradiation prior to injection of the donor cells. Donor cells can be genetically manipulated by lipofection mediated gene transfer before they are introduced into the recipient. The genetic modification is expressed in the ectoderm, mesoderm, and endoderm of the chimera after incubation for 96 h. Donor cells can also be cultured as dispersed cells in a monolayer or as whole-embryo explants for at least 48 h before transfer into recipients and retain the ability to enter both somatic and germline tissues in the resulting chimera. A strategy is proposed for the production of transgenic chickens using lipofection-mediated gene transfer to blastoderm cells isolated from Stage X embryos, which are subsequently injected into compromised recipients to yield a germline chimera. PMID- 8502611 TI - Genetic control of sex determination in birds and the potential for its manipulation. AB - The sex determination systems of Drosophila, birds, marsupial mammals, and eutherian mammals are briefly reviewed. Evidence from poultry polyploids, aneuploids, and gynandromorphs suggests that avian sex is determined by Z to autosome ratio and also that avian sex-limited traits may be under both cell autonomous and hormonal controls. To identify aneuploids in avian populations, a cDNA clone linked to both the Z and W chromosomes of many avian groups was used to screen large numbers of psittacine birds and identified five birds with atypical patterns of restriction fragments. Two of these birds were examined by laparoscopy and found to be intersexes. These preliminary observations indicate that structural changes in the Z and W chromosomes result in alterations of sex determination. PMID- 8502612 TI - Photoperiodic control of reproduction in the domestic hen. AB - Egg laying in domestic hens exposed to natural lighting begins shortly after the winter solstice, peaks in early spring, begins to decrease before the fall equinox, and is at its lowest during the late fall and early winter. The seasonal cycle of egg production phase-leads that of the changes in day length. This seeming anomaly can be explained if it is accepted that 1) short days are photoperiodically neutral and do not actively inhibit gonadotropin-releasing hormone (GnRH)-I neurons; and 2) long days are photoperiodically active, transducing both stimulatory and inhibitory inputs to GnRH-I neurons. The development of a long day-induced inhibitory input results in a form of photorefractoriness. Around the winter solstice, photorefractoriness is dissipated by prolonged exposure to short days, allowing GnRH-I neurons to express a photoperiodic-independent, genotype-dependent, level of activity. This is sufficient to stimulate egg laying before the minimum photoperiod for photoinduced gonadotropin release is reached in early spring. When day length begins to decrease after the summer solstice, the photoinduced stimulatory input to GnRH-I neurons is reduced, unmasking the photoinduced inhibitory input. As a consequence, the activity of GnRH-I neurons decreases rapidly and the intensity of egg laying decreases. The minimum and maximum day lengths required to stimulate reproductive function in short-day hens, calculated from the photoperiodic response curves (PRC) for luteinizing hormone release are about 10 and 13 h, respectively, depending on genotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502613 TI - Sperm storage and transport following natural mating and artificial insemination. AB - Recent observations in turkey and chicken hens show that sperm storage in both species is a highly inefficient process. After artificial insemination (AI), less than 1% of spermatozoa inseminated are selected for transport to and enter the sperm storage tubules (SST). It has been shown that the sperm selection process is orchestrated within the vagina and not at the level of the SST. At least two mechanisms are involved in the selection of spermatozoa fit for sperm storage, one being mechanical (motility) and the other biochemical in nature (sperm vaginal mucosa interactions). Furthermore, it was also observed that the sperm storage efficiency in the chicken is dependent upon the logarithm of the number of spermatozoa inseminated. From a practical standpoint, inseminations performed frequently with a moderate number of spermatozoa should be more efficient than inseminations performed with higher doses at longer intervals. Maximal filling of the SST of hens in egg production requires only 1 day for the chicken and 2 days for the turkey. By contrast, the release of sperm from the SST is about seven times faster in the chicken than the turkey hen. The efficiency of oviducal sperm storage is related to a number of factors including age of the hen, stage of the ovulatory cycle when inseminated, and, in the turkey, if the hen was inseminated before or after the onset of egg production. Two different categories should be considered among factors that affect sperm survival in vivo. 1) Factors affecting sperm storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502614 TI - The median eminence as a site for neuroendocrine control of reproduction in hens. AB - Based on events occurring during the genesis of a preovulatory surge of luteinizing hormone (LH) and an ovulatory failure of central origin, the hypothalamic median eminence (ME) is probably a major neuroendocrine control site for reproductive activity in the hen. The ratio of facilitatory to inhibitory (F:I) inputs on LH-releasing hormone (LHRH) neuronal terminals is an important determinant of the ME control site. The word "facilitatory" is defined as "stimulatory or increasing responsiveness to inputs". A relative increase in the F:I ratio of inputs on LHRH neuronal terminals at the ME is apparently involved in the genesis of the preovulatory surge of LH. Both an increase in neuropeptide Y (NPY) facilitatory inputs and a decrease in beta-endorphin (beta END) inhibitory inputs to ME-LHRH neuronal terminals are involved in the increase in the F:I ratio preceding the preovulatory surge of LH. Although the NPY component of this ratio (F) is apparently driven by the preovulatory surge of progesterone (P4) itself, its beta END component (I) might be related to the preovulatory surge of estradiol accompanying or preceding that of P4. As the egg-producing life of the hen progresses, a relative decrease in the F:I ratio on ME-LHRH neuronal terminals occurs. As a consequence of this decrease, stress-related inputs (e.g., feed restriction) can induce an hypothalamic failure of central origin in laying hens ending their 1st yr of production, but not in birds at the start of their egg-laying life. An increase in ME dopaminergic inhibitory inputs (I) on LHRH neuronal terminals is an apparent cause of the ovulatory failure induced by feed restriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502615 TI - A microscopist's view of poultry reproductive tracts and gametes. AB - The investigator using light or electron microscopy to elucidate the histology and ultrastructure of the reproductive organs and gametes of chickens and turkeys is confronted with unique problems. This paper addresses these as well as other more general concerns regarding specimen preparation and laboratory safety. The use of differential interference contrast microscopy coupled with fluorescence microscopy as a means to study the fate of sperm in the oviduct is introduced. PMID- 8502616 TI - Cryopreservation of rooster sperm. AB - Successful cryopreservation of sperm requires: 1) selection of proper diluent; 2) selection of the best cryoprotectant; 3) determination of freezing and thawing rates for optimum retention of fertilization potential; and 4) removal of any materials deleterious to fertility (e.g., glycerol) before insemination. An economically useful process must allow recovery of sperm with sufficient fertilization capacity to enable maximum use of any given superior male. A series of experiments tested a novel semen freezing container (BioPore CryoCell container) having physical characteristics that permit reproducible freezing and thawing plus facile removal of glycerol from the sample after processing. Experiments tested the effect of: a) residual glycerol; b) initial glycerol concentrations on retention of fertility when samples were frozen and thawed at 6 C/min; c) Beltsville Poultry Semen Extender and Minnesota A buffers used during the dialysis procedure; and d) dialysis time. Respectively, the results were: a) .8% (vol/vol) reduced fertility by 5 to 10%; b) 12% glycerol was superior to 10% and 8% glycerol; c) no difference was observed between the two buffers; and d) 90 and 120 min were both superior to 60 min. Numerous pools of rooster sperm cryopreserved in CryoCell containers and dialyzed after thawing in a prototype BioStore environmental control chamber for 90 or 120 min resulted in a mean fertility of 55.6%. This mean fertility of frozen-thawed sperm was based on 3,263 eggs laid by 400 hens on Days +1 through 9 after inseminations on Days -1, 2, and 5. It is likely that broiler stocks might have lower fertility than that obtained from the Barred Plymouth Rock males and the Single Comb White Leghorn females used in these studies. Nevertheless, the procedure described is the first to consistently result in > 50% fertilized eggs as a result of conventional intravaginal insemination (< 200 x 10(6) sperm in 100 microL extender) of sperm processed after thawing by a procedure amenable to the scaleup required for commercial applications. PMID- 8502617 TI - Inhibin in the hen. AB - The role of the gonadal hormone inhibin has not been extensively examined in the hen. A bovine radioimmunoassay kit has been used to assess plasma levels of immunoreactive inhibin throughout the ovulatory cycle, in response to follicle removal, and after stimulation of follicle growth. Homologous chicken radioimmunoassays for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were used to assay plasma gonadotropins. No significant peak of immunoreactive inhibin was detected throughout the ovulatory cycle in spite of a preovulatory surge of LH. Removal of preovulatory follicles caused a decrease of plasma immunoreactive inhibin whereas stimulation of follicle growth with equine chorionic gonadotropin increased plasma immunoreactive inhibin levels. Associated with the fall in inhibin level upon follicle removal is an acute rise in FSH with no concomitant change in LH. PMID- 8502618 TI - The search for deep encephalic photoreceptors within the avian brain, using gonadal development as a primary indicator. AB - A review of the literature was completed on central neural structures regarded to be the site of encephalic photoreceptors in avian species. The photoreceptors are thought to function as endogenous clocks, respond to certain lengths and characteristics of the photoperiod, and serve to activate important physiological events such as gonadal function at the optimal season or time each year. Three sites have been explored: eyes, pineal gland, and deep encephalic photoreceptors within the ventral forebrain. To date the evidence supports the latter as the best candidate for housing specialized neuroendocrine photoreceptors. Within the ventral forebrain, most studies have concentrated on the medial basal hypothalamus (also known as the infundibular tuberal complex), however a second locus, the lobus parolfactorius, has also been identified. Specifically, a group of cerebrospinal fluid (CSF)-contacting neurons in the medial portion of the lateral septal organ (LSO) within the lobus parolfactorius is a second viable candidate. The chick appears to be an excellent model to determine whether or not the CSF-contacting neurons of the medial LSO are deep encephalic photoreceptors. PMID- 8502619 TI - Research note: pharmacokinetics of aditoprim in turkeys after intravenous and oral administration. AB - The pharmacokinetics of aditoprim, a not yet commercialized selective reversible inhibitor of dihydrofolate reductase, were determined in turkeys after intravenous (5 mg/kg BW) and oral (5.46 +/- .44 mg/kg BW) administration. The mean (+/- SD) total body clearance of 26.9 +/- 2.3 mL/min per kg BW was high when compared with that determined for other species, presumably a consequence of the higher metabolic rate of birds. Consequently, mean aditoprim elimination half life was relatively short (3.3 +/- .2 h). As determined in mammalian species, the apparent volume of distribution at steady state was large. Aditoprim in drinking water (100 and 300 mg/L water) provided plasma concentrations between .08 and .19 micrograms/mL. Circadian rhythms with highest concentrations in the late afternoon and lowest concentrations in the morning were observed. Despite its short elimination half-life, aditoprim may still be a valuable antimicrobial for use in avian medicine pending safety, efficacy, and residue depletion studies. PMID- 8502620 TI - Experimental autoimmune anterior uveitis (EAAU): induction by melanin antigen and suppression by various treatments. AB - The uveitogenicity of melanin has been a controversial subject for a long time, presumably as a result of the use of ill-defined preparations in the experiments. We have developed procedures for the preparation of purified uveitogenic melanins from the retinal pigment epithelium and choroid that are free from pathogenic retinal photoreceptor proteins. The active melano-antigen is located at the surface of the melanin granules and is probably identical in both tissues. It retains its pathogenicity in hot polar detergent and during in vitro proteolysis, but it is inactivated by macrophage phagocytosis and hydrolysis in hot hydrochloric acid. Lewis rats immunized with microgram doses of bovine retinal pigment epithelial or choroidal melanin develop severe experimental autoimmune anterior uveitis (EAAU) about 10 days later. Retinitis and pinealitis are not observed. Skin melanin prepared in a similar way evokes EAAU as well, but it is only weakly pathogenic. EAAU cannot be transferred by serum, and its development can effectively be inhibited by antibodies to the inciting antigen and by cyclosporin. Vitamin E treatment of the animals causes a delay in its onset. The results indicate that cell-mediated immunity plays a dominant role in the pathogenesis of EAAU. This is the first time it has been shown that purified ocular and skin melanins are able to induce an autoimmune disease. The relevance of this finding for the study of melanin-related immunopathology in man is discussed. PMID- 8502621 TI - In vivo and in vitro expression of octamer binding proteins in human melanoma metastases, brain tissue, and fibroblasts. AB - The pattern of octamer sequence-specific DNA binding proteins expressed in human melanoma was examined in nuclear extracts of seven surgically-isolated tumors, short-term cultures of these tumors, and 25 human melanoma cell lines to determine the in vivo and in vitro distribution of the melanocytic-associated Oct M1 and Oct-M2 octamer binding activities. In the biopsy tissue and cultured melanoma cells of a metastasis from the cerebellum, two other binding activities (N-Oct-2 and N-Oct-6) in addition to the Oct-M1, Oct-M2 and the generally expressed Oct-1 protein were detected; this profile was consistent with that seen in normal human and mouse brain tissue. Melanoma tissue removed from lymph nodes and cell lines established from them also showed Oct-1, Oct-M1, Oct-M2, and N-Oct 2. N-Oct-2 was distinguished from the comigrating Oct-2A activity by failure to react with Oct-2A-specific antibody. All but one of the 25 melanoma cell lines exhibited Oct-1, Oct-M1, and Oct-M2 and/or N-Oct-2 activity, whereas cultured normal melanocytes expressed only Oct-1 and Oct-M1. In contrast to murine fibroblasts, which express only Oct-1, human fibroblast strains also expressed Oct-2A binding activity, which was confirmed by reactivity with Oct-2A antibody and the presence of Oct-2A mRNA and indicated that Oct-2A has a more general role than that of a lymphoid-specific transcription factor. Overall, the results indicate that expression of neural-specific Oct factors in human melanoma is (1) aberrant compared with normal melanocytes, (2) can be modulated by the surrounding tissue in a brain metastasis, and (3) may be part of the altered program of differentiation accompanying transformation. PMID- 8502622 TI - Vitiligo in two water buffaloes: histological, histochemical, and ultrastructural investigations. AB - Vitiligo, a skin disease, characterized by the spontaneous loss of melanin, has been described in several animals as well as in humans. Most of the reports of large domestic animals have dealt with clinical investigations without morphological data. In this report, the histological and ultrastructural characteristics of two cases of vitiligo in water buffaloes (Bubalus bubalis) are presented. Interestingly, many of the ultrastructural observations for vitiliginous buffaloes resemble those previously described for other species, e.g., humans, mouse, and chicken. These data suggest that one or more forms of human vitiligo may have a similar etiopathogenesis to that of the buffalo. Therefore, it is proposed that vitiliginous buffalo may prove to be a useful animal model for the human disease. PMID- 8502623 TI - Circadian motile activity of erythrophores in the red abdominal skin of tetra fishes and its possible significance in chromatic adaptation. AB - The red abdominal skin of the neon tetra Paracheirodon innesi and the cardinal tetra P. axelrodi was found to blanch at night or in the dark. Melatonin added to the bathing medium caused blanching of the red skin. Microscopic observations of the erythrophores indicated that the erythrosomes aggregated in response to norepinephrine, melanin-concentrating hormone (MCH), and melatonin. Of these compounds, melatonin was the most effective. By contrast, many erythrophores were refractory to MCH. Alpha-melanophore-stimulating hormone, isoproterenol, adenosine, and ATP each caused dispersal of the pigment to some extent. Isoproterenol dispersed the pigment only when an alpha-adrenergic blocker, tolazoline, was present. It appears that the change in color of the abdominal skin is primarily due to increased secretion during the night of the pineal hormone melatonin, while other hormonal and nervous factors may modify the distribution of the pigment in the erythrophores. PMID- 8502624 TI - Muscarinic cholinoceptors that mediate pigment aggregation are present in the melanophores of cyprinids (Zacco spp.). AB - Like melanophores of many teleosts, those of the dark chub, Zacco temmincki, and the common minnow, Z. platypus (Cyprinidae, Cypriniformes) responded to norepinephrine (NE) by the aggregation of pigment. It was further found that some melanophores were responsive to acetylcholine (ACh) in the same way. The response to NE was blocked by an alpha-adrenergic blocker, phentolamine, whereas the response to ACh was not. By contrast, two muscarinic cholinoceptor antagonists, namely, atropine and scopolamine, effectively blocked the action of ACh. The pigment aggregation due to the liberated sympathetic neurotransmitter was blocked by phentolamine but not by cholinergic blockers. These results suggest that, although the melanophores of these species are controlled in an orthodox manner by the sympathetic nervous system, some of them possess extra muscarinic cholinoceptors that also mediate the aggregation of pigment. The present report is the first to describe the presence of cholinoceptors on the chromatophores in species of fish other than those that belong to the order Siluriformes. The evolutionary implications of these findings are discussed. PMID- 8502625 TI - Deficiency of the gene B impairs differentiation of melanophores in the medaka fish, Oryzias latipes: fine structure studies. AB - In an orange-colored variant of the medaka fish, Oryzias latipes, which is homozygous for b allele, the melanophores represent a tissue-specific differentiation, manifesting an amelanotic appearance in the skin, an incomplete melanogenesis in the choroid and the peritoneum, and mosaic phenotype-like melano iridophores in the peritoneum. In a wild-type strain of this species carrying the B gene, all melanophores are terminally differentiated irrespective of the tissues in which they are located. This indicates that the deficiency of B gene impairs the differentiation of melanophores in the medaka. Electron microscopy disclosed that the deficiency of B gene causes deterioration of melanogenesis to occur inside the melanosomes and that the manner of deterioration in the melanophores in the skin, the choroid and the peritoneum is different. The ubiquitous occurrence of reflecting platelet-laden melanophores in the peritoneum of this variant and the total absence of a mosaicism in pigment cells of the wild type strain indicate that the deficiency of B gene predestines melanoblasts distributed in this tissue to an ambiguous state with regard to their differentiation. Little difference is observed between melanosomes maturation in pigment epithelial cells of the orange-colored variant and the wild-type strain, indicating an innocent role of the B gene in their differentiation. PMID- 8502626 TI - Isolation and characterization of high molecular weight melanogenic inhibitors naturally occurring in melanoma cells. AB - Intrinsic melanogenic inhibitors with high molecular weights have been isolated from Greene's amelanotic hamster melanoma by DEAE ion-exchange and gel filtration chromatographies. The native molecular weights of two partially purified inhibitors have been determined to be 15 kDa (beta-type) and 67 kDa (gamma-type), respectively, using HPLC gel filtration. Both types of inhibitors, despite their inability to directly inhibit isolated tyrosinase, have been shown to markedly inhibit melanin formation in cultured B16 cells. In contrast to the beta-type inhibitor, the gamma-type inhibitor can induce depigmentation in B16 cells without abolishing their internal tyrosinase activity. Further, it has been determined that both inhibitors contain various amounts of unsaturated fatty acids, C15:1, C18:1, C18:2, C18:3, C20:3, and C20:4, which exhibit depigmentary activities on cultured B16 cells. C15:1 is low in the beta-type, but high in the gamma-type whereas C18:3 is high in the beta-type but low in the gamma-type. These results suggest that the differential action of these inhibitors is most likely due to the composition of the unsaturated fatty acids. PMID- 8502627 TI - [Acute cystitis in women over 50 years of age. Efficacy of pefloxacin with single dose and norfloxacin for 10 days]. AB - This multicentre, open, randomized trial, involving 482 patients and conducted by private practitioners, compared the effectiveness and safety of a single 800 mg dose of pefloxacin and of a 10 days' course of norfloxacin 400 mg bid. in the treatment of uncomplicated acute cystitis in women aged over 50 years. Clinical effectiveness was evaluated on days 17-19 and 28-32 respectively, and bacteriological effectiveness on days 15-17 and 26-28 respectively. The median time taken for the symptoms to disappear was 2 days with pefloxacin and 3 days with norfloxacin (P < 0.001). Irrespective of the nature of cystitis and the patients' age, no significant difference could be found in eradication of the pathogens. Undesirable side-effects were recorded in 7.8 percent of patients under pefloxacin and in 8.8 percent of those under norfloxacin (P = 0.68); gastrointestinal disorders were predominant. The acceptability of treatment, as judged by the patients themselves, was regarded as excellent by 55 percent of women treated with single dose pefloxacin and by 37.6 percent of those treated with norfloxacin (P = 0.001). PMID- 8502628 TI - [Synchronization of plasma exchange and cyclophosphamide in severe systemic diseases. A consecutive study of 10 patients]. AB - Ten patients with severe systemic diseases, including systemic lupus erythematosus (n = 2), polymyositis (n = 2), essential mixed cryoglobulinaemia (n = 2), rheumatoid arthritis vasculitis (n = 3) and Wegener's granulomatosis (n = 1), were treated with 3 consecutive plasma exchanges synchronized with pulse cyclophosphamide. This therapeutic regimen was applied every 4 weeks initially and thereafter every 6 weeks in case of positive response after the first 3 cycles; it was combined in all patients with corticosteroid therapy. The treatment was administered for severe flare-up of the disease in 7 patients and for failure of previous treatments, including corticosteroids, cyclophosphamide and plasmapheresis, in 3 patients. Three kinds of response were observed: lasting complete remission without relapse after synchronization had ceased in 4 patients, partial clinical remission with post-synchronization relapse in 5 patients, and primary failure without any clinical response to treatment in only 1 patient. These results suggest that repeated plasma exchanges synchronized with cyclophosphamide are effective against progressive autoimmune diseases and in cases where conventionally administered immunosuppressive treatments had failed. However, this type of treatment cannot prevent long-term relapses, and only a prospective study can evaluate its success in terms of survival. PMID- 8502629 TI - [Prolactin adenoma developed during puberty. Diagnosis and long-term course. 9 cases]. AB - Nine patients (2 boys, 7 girls) with prolactinomas diagnosed at puberty were followed for 2 to 20 years. The presenting signs were sexual infantilism (n = 2), amenorrhea-galactorrhea (n = 6) and hypogonadism (n = 1). Growth retardation was also present in 3 cases. The pituitary tumor induced endocranial manifestations in only 2 cases, whereas a suprasellar extension was found in 5 cases with visual field defects in 2 cases. Initial prolactin levels ranged between 132 and 2,400 ng/ml and were unresponsive to TRH (n = 6/7). The hormonal work-up showed decreased GH (n = 4/4); LH, FSH (n = 9/9) or ACTH, TSH (n = 1/9) functions. Seven patients underwent trans-sphenoidal adenomectomy associated with dopaminergic agonist treatment. Two patients were treated with bromocriptine. In the long term, clinical signs (n = 6), hyperprolactinemia (n = 7) or prolactinoma (n = 4) persisted or recurred. These data stress the severity of this disease at this period of life, the therapeutic difficulties and the need for long term follow up of these patients. PMID- 8502630 TI - [Fibrillary glomerulopathies]. AB - Fibrillary glomerulonephritis is characterized by the presence, mainly in the mesangium, of fibrils demonstrated by electron microscopy of the renal parenchyma. There are several varieties of this disease, depending on the size and, above all, the composition of these fibrils. Thus, fibrillary glomerulonephritis in which the fibrils are made of the normal glomerular basement membrane components can be distinguished from a more frequent variety in which the fibrils are composed of circulating proteins deposited in glomeruli. For a long time, amyloid glomerular nephropathy has been the sole representative of the latter variety, but we now know that, beside renal amyloidosis, there is a non-amyloid fibrillary glomerulonephritis the fibrils of which are made of monoclonal or non-monoclonal immunoglobulins. If it were confirmed that the principal member of this variety, described as immunotactoid glomerulopathy, is frequently associated with monoclonal gammapathy, it would represent, together with amyloidosis and light chain deposition, another variety of glomerular lesions which may occur in monoclonal gammapathy. PMID- 8502631 TI - [Microalbuminuria, paucialbuminuria or oligoalbuminuria?]. PMID- 8502632 TI - [Tamponade complicating thrombolysis of clots in the right cardiac cavities following myocardial infarction]. PMID- 8502633 TI - [Convulsive seizures after prevention with chloroquine]. PMID- 8502634 TI - [Listeria monocytogenes in patients with human immunodeficiency virus infection. 2 cases]. PMID- 8502635 TI - [Hypercalcemia, 2 associated mechanisms. Value of the couple assay of parathormone-related hormone and parathormone]. PMID- 8502637 TI - [Febrile pancytopenia in AIDS. Value of bone marrow cell count in the early diagnosis of opportunistic infections]. PMID- 8502636 TI - [Pulmonary replantation. 8 cases among 29 long-term survivors]. PMID- 8502638 TI - [Association of disseminated lupus erythematosus and Hashimoto's thyroiditis. 2 new cases]. PMID- 8502639 TI - [Iliac arterial injuries during celiosurgery]. PMID- 8502640 TI - [Appetite comes with eating, cortisol too. A new cause of Cushing's syndrome]. PMID- 8502641 TI - [Bladder-sphincter complications after peridural anesthesia. 8 cases]. AB - Eight cases of vesico-sphincteric disorders (dysuria and chronic retention of urine) observed after spinal anaesthesia are reported. These symptomatic disorders were caused by a peridural haematoma in 3 cases and by lack of bladder contraction due to an "exhausted detrusor muscle" in 5 cases. The mechanism of the disorders (predominant vesical hypoactivity with sensory disorders) is discussed. The usefulness of urodynamic investigation in determining the physiopathological mechanism(s) and that of electrophysiological exploration in the search for a neurogenic disease is emphasized, as is the need for a preventing treatment (intermittent catheterization) in case of forced bladder detected by systematic recording of postoperative micturitions. PMID- 8502642 TI - [Infectious complications during treatments with interleukin-2]. AB - Between January 1989 and May 1991, 97 patients were treated with interleukin 2 in the Oncology Department of the Avicenne Hospital (Bobigny, France). IL 2 was given over 5 days by continuous infusion through an implantable port. Ten patients (4 males, 6 females), mean age 46 years (36-67) with various cancers (breast 3, kidney 1, melanoma 1, colorectal 5), developed infection: 4 local infections around the port, 1 phlebitis, 4 septicemias, 1 bacteremia were observed. In 9 cases blood cultures were positive: Staphylococcus aureus 5, Staphylococcus epidermidis 3, Streptococcus G 1. In 5 cases the same pathogen was isolated from the port and from the blood. The mean leucocyte count was 10,627/mm3 at the time of infection. The delay between the beginning of interleukin 2 treatment and the infection was 3 months. The mean dose of IL 2 administered before infection was 456 million IU. In all cases infection was controlled without lethal complication by antibiotics and catheter removal. This high incidence (8 percent) of staphylococcal infection is partly due to the skin toxicity of IL 2 and to depressed neutrophil chemotactic response. Prophylactic antibiotics are warranted during IL 2 intravenous therapy. PMID- 8502643 TI - [Treatment of skin lesions. Contribution of tissue expansion]. AB - We report our experience of tissue expansion for removal of skin tumors in 62 patients treated between 1985 and 1991. Thirty-nine complete and 23 partial excisions were performed. Major complications with complete failure occurred in 3 percent of the cases, and minor complications in 10 percent. Skin expansion constitutes a considerable advance in the treatment of benign skin tumors as it reduces the risk of permanent scars and provides a skin that is normal in both quality and colour. In cases where the tumor cannot be entirely removed in one step (e.g. giant hairy naevus, haemolymphangioma) expansion brings quality skin within the most visible areas, enabling complete excisions by re-expansion or skin graft to be contemplated. PMID- 8502644 TI - [Deglutition disorders in Lyme disease with severe neurological involvement]. AB - A 67-year old man consulted for dysphagia to solid food and weight loss. Four years earlier he had developed Lyme disease with severe neurological involvement. Magnetic resonance imaging showed, on T2-weighted sequences, multifocal high intensity signals located in the periventricular white matter and the brain stem. The disorders of deglutition were evaluated by cineradiography and manometry which showed deficient relaxation of the superior esophageal sphincter and delayed initiation of the pharyngeal phase; intrapharyngeal propulsion was preserved. On the basis of these findings cricopharyngeal myotomy was performed with subsequent improvement of the disorders. Treatment with doxycycline was prescribed. The significance of these deglutition disorders as regards infection and neurology is discussed and it should have therapeutic implications. PMID- 8502646 TI - [Transanal excision of villous tumors. Value of the Endo-GIA 30 Multifire clamp]. AB - The authors describe a new surgical procedure applied to the treatment of villous adenoma of the rectum. The mechanical device called Endo-GIA 30 Multifire (Merlin Medical, F69672 Bron), an automatic suture clamp regularly used in laparoscopic surgery, facilitates complete excision of villous adenomas if the tumour is located less than 10 cm from the anal margin. PMID- 8502645 TI - [Diagnosis of acute infectious epidural inflammation. Role of magnetic resonance imaging]. AB - External pachymeningitis, usually caused by Staphylococcus aureus, is a rare pathological entity which is difficult to diagnose at an early stage, has a poor functional prognosis and often requires an emergency surgical treatment. We report three cases in which magnetic resonance imaging provided an early diagnosis of the epidural space infection before severe neurological deficits, such as paraparesis and/or paraplegia, set in. Following an anti-staphylococcal treatment with fluoroquinolone and beta-lactamase-resistant beta-lactam antibiotics with good bone penetration administered intravenously during 4 to 6 weeks, then orally for 5 to 6 months cure without functional sequelae was obtained in all three patients. PMID- 8502647 TI - [Sex steroids. Effects on the carbohydrate metabolism before and after menopause]. AB - The action of female sex steroids on carbohydrate metabolism has clearly been demonstrated by numerous clinical and experimental studies. A beneficial effect of 17 beta oestradiol has been reported on insulin secretion and insulin sensitivity, inducing an improvement of glucose tolerance through an increase of glucose clearance by liver, muscle and adipose tissues. Progesterone has, to a lesser degree, the same stimulant effect on insulin secretion and improves glucose assimilation by the liver, although a relative insulin resistance is observed in the other two tissues. Menopausal hormonal privation does not significantly alter glucose tolerance in the absence of such predisposition factors as overweight or history of gestational or familial diabetes mellitus. The first trials of menopausal substitution with oral synthetic oestrogens, especially in doses of more than 50 micrograms per day, were responsible for the bad reputation of oestroprogestins due to their effects on metabolic parameters. As shown by prescription for contraceptive use, replacement therapy with oral synthetic oestrogens induces a diabetogenic tendency as well as hypertensive, dyslipidaemic and thrombogenic risks, especially when associated with progestins issued from nortestosterone. Reducing the oestrogen doses, using equine sulfoconjugates and selecting non-androgenic progestins has already minimized these deleterious effects. The present availability of oral or percutaneous natural 17 beta oestradiol and of norpregnanes calls for reconsideration of the glucidic risk due to oestroprogestin prescription. A few studies have already shown that in fact they can improve glucose tolerance. The recommended substitution of menopause to prevent atherosclerosis must lead to a better characterization of its glycaemic and insulinaemic effects. PMID- 8502648 TI - [Respiratory virus infections in children]. AB - Eighty to ninety percent of pathogens responsible for acute respiratory infections in children are viruses, but despite advances in virology these organisms are isolated in only 20 to 45 percent of the cases. Studies conducted outside hospitals have provided epidemiological data. The virus most frequently encountered is the respiratory syncytial virus. The main clinical feature of these respiratory viral infections is obstruction of the bronchioles, and their immediate or delayed danger is the risk of chronic obstructive bronchitis. Treatment is symptomatic, but specific antiviral agents, notably ribavirin, are useful in severe infections. PMID- 8502649 TI - [Decalcifying algo-neurodystrophy, osteomalacia, tubulopathy...]. PMID- 8502650 TI - [Gemella haemolysans purulent meningitis]. PMID- 8502651 TI - [Arcanobacterium haemolyticum angina]. PMID- 8502652 TI - [Cutaneous vasculitis and acute renal failure disclosing endocarditis caused by Actinobacillus actinomycetemcomitans]. PMID- 8502653 TI - Site-specific initiation of transcription by RNA polymerase II. AB - RNA polymerase II initiates transcription at specific DNA sequences. Studies using sequence analysis and molecular genetics suggest a simple and universal model of start-site selection by RNA polymerase II. Two consensus sequences occur at fixed positions in promoters from higher eukaryotes and their viruses: the TATA box around -30 and the initiator at the start site of transcription. Both consensus sequences function as positioning elements that control site-specific initiation. As a first step during initiation, the basal transcription factor TFIID binds to the TATA box; regulatory transcription factors can tether TFIID bind to the TATA box; regulatory transcription factors can tether TFIID to promoters without a consensus TATA box. TFIID then directs the assembly of other basal transcription factors and RNA polymerase II into a preinitiation complex. Finally, RNA polymerase II searches for the best match to the initiator consensus about 30 base pairs downstream of the TATA box to select the exact start site. The transcriptional activity of a start-site sequence generally correlates with its similarity to the initiator consensus, suggesting that there is only one type of initiator. PMID- 8502654 TI - Perspectives on intracellular storage and transport of cationic-lipophilic drugs. PMID- 8502655 TI - Role of renal nerves in renal responses to acute volume expansion during pregnancy in rats. AB - To examine the role of the renal nerves in renal responses to acute volume expansion (VE) at Days 17-19 of pregnancy in rats, the diuretic and natriuretic responses to acute VE were measured from intact and denervated kidneys. One group of pregnant rats (Pregnant 1) was treated with the same amount of VE (1 ml/min for 15 min) as age -and sex-matched virgin control rats, and a second group of pregnant rats (Pregnant 2) was treated with a VE corrected for the higher body weight (presumably expanded blood volume) normally observed in late pregnancy (1.38 ml/min for 15 min). Urine flow and sodium excretion were measured before and after VE from innervated and denervated kidneys in anesthetized (Inactin) rats. Mean arterial pressure was not significantly different among the groups. During VE, the increments in urinary flow (UV) rate and sodium excretion (UNaV) from the innervated kidneys of Pregnant 1 rats were significantly smaller (26.5% for UV and 17.0% for UNaV) than those from the innervated kidneys of virgin rats. Although the UV and UNaV were greater in the Pregnant 2 group than in the Pregnant 1 group, these differences were not statistically significant. However, the values were still significantly smaller than those observed in the control group (39.1% for UV and 52.8% for UNaV). Urine flow and sodium excretion from the denervated kidneys of pregnant rats (both groups) were not significantly different from those of denervated kidneys of control rats. These results demonstrate that the reduced diuresis and natriuresis observed during acute volume expansion in pregnant rats may be due to the contribution of tonic renal nerve activity during the third week of pregnancy. PMID- 8502656 TI - Role of angiotensin II receptors in tail skin temperature response to isoproterenol. AB - The objective of these experiments was to assess the possibility that the increase in tail skin temperature (TSK) accompanying administration of the beta adrenergic agonist isoproterenol (ISO) was mediated by angiotensin II (AngII) as a result of stimulation of renin release by ISO. Although AngII is known to be a potent vasoconstrictor in mammals, acute administration of this peptide to rats induces a vasodilation of blood vessels in the tail and an increase in TSK. The objective was approached in several (DuP 753); ways: (i) use of the nonpeptide AngII receptor antagonist losartan potassium (DuP 753); (ii) use of the peptide AngII receptor antagonist saralasin; (iii) use of the AngI-converting enzyme inhibitor captopril, and (iv) chronic administration of AngII. The rationale for these experiments was that blockade of AngII receptors (Experiments 1 and 2), inhibition of the enzyme that converts AngI to AngII (Experiment 3), or down regulation of the AngII receptors (Experiment 4) would be expected to prevent any contribution to the ISO-induced increase in TSK by AngII. The results of these experiments are consistent in revealing that the response of TSK to ISO administration is due in part (approximately 55%) to a direct effect of ISO and in part (approximately 45%) to an indirect effect resulting from the ISO stimulated release of renin from the kidneys and the formation of AngII in the blood. PMID- 8502657 TI - Early renal disease in BHE/cdb rats is less in rats fed beef tallow than in rats fed menhaden oil. AB - The effects of feeding a 1% corn oil-9% menhaden oil or beef tallow diet on the early phase of diabetic nephropathy in BHE/cdb rats was studied. The diet groups were subdivided into rats with or without impaired glucose tolerance. Those fed menhaden oil had renal hypertrophy, mild albuminuria, decreased creatinine clearance, increased urea clearance, and more severe lesion scores than rats fed beef tallow. No differences in glomerular filtration rate, Na+, K+-ATPase activity, sorbitol dehydrogenase, or inositol 1, 4, 5-phosphate were observed. Beef tallow-fed rats had higher serum triglyceride levels and renal cholesterol levels. Renal and hepatic fatty acid profiles reflected the fatty acid profile of the dietary fat. These results suggest that beef tallow conferred a protective effect on the renal tissues of these diabetes-prone rats. PMID- 8502658 TI - Nutritional regulation of insulin-sensitive glucose transporter gene expression in rat cardiac muscle. AB - The effects of fasting and refeeding on the levels of mRNA encoding the insulin sensitive glucose transporter (GLUT4) in rat cardiac and skeletal muscle were investigated using solution hybridization/RNase protection assays with a rat GLUT4 antisense RNA probe. In addition, the effects of these nutritional states on GLUT1 mRNA levels in several non-insulin-sensitive tissues were examined using a GLUT1 antisense RNA probe. Fasting for 48 hr significantly decreased GLUT4 mRNA levels in heart, with levels significantly increased over control levels by 24 hr after refeeding. In contrast, GLUT4 mRNA levels in skeletal muscle increased with fasting and returned to control levels with refeeding. No significant changes in GLUT1 mRNA were seen after fasting and refeeding in several non-insulin-sensitive tissues studied. These results suggest that altered GLUT4 gene expression is observed in different nutritional (insulin) states in insulin-sensitive tissues, and suggests a potential role for insulin in mediating these changes in gene expression. PMID- 8502659 TI - Effects of H-2 and dietary vitamin A on the frequency of dorsoventral vaginal septum. AB - The frequency of dorsoventral vaginal septum (DVS) in mice is determined in part by genes associated with the major histocompatibility complex H-2. Data presented here confirm that one locus (DVS-1) maps centromeric to E alpha and that the second (DVS-2), previously shown to be associated with the S-to-D region, maps to the C4:B144 interval, most likely between Dcp-2 which contributes to glucocorticoid-induced cleft palate susceptibility and Acp which enhances cleft palate susceptibility through the action of vitamin A. Comparisons of data obtained in this laboratory in the periods 1981-1983 and 1985-1990 and observations from the production colony from which many of the strains were purchased revealed minor variations in frequencies of DVS within strains which may be due to differences in ascertainment and/or to environmental factors. The addition of vitamin A to the diet of pregnant mice at a dose that increases the frequency of cleft palate in susceptible strains had no effect on the incidence of DVS. PMID- 8502660 TI - Sleep as a prognostic indicator during infectious disease in rabbits. AB - Infectious disease alters sleep patterns in rabbits, but the recuperative value of enhanced sleep during infectious disease has not been experimentally verified. To evaluate the relationship between specific sleep patterns and the clinical response to infectious disease, we classified sleep patterns in rabbits inoculated with E. coli, S. aureus, or C. albicans on the basis of the duration of the period of enhanced sleep. Patterns characterized by a long period of enhanced sleep were associated with a more favorable prognosis and less severe clinical signs than were patterns characterized by relatively short periods of enhanced sleep followed by prolonged sleep suppression. A contrasting analysis of these data indicated that animals that eventually died demonstrated reduced sleep compared to rabbits that survived the infection. These observations are consistent with the hypothesis that dynamic changes in sleep over the course of an infectious disease aid in recuperation. PMID- 8502661 TI - Tumor necrosis factor induces enzymatic changes in liver comparable to those in extrahepatic cancer. AB - Human recombinant tumor necrosis factor was administered to rats in small doses to determine whether it causes changes in the activity of liver enzymes similar to those observed in cancer growing extrahepatically. Intraperitoneal injection of increasing doses of tumor necrosis factor (20-100 micrograms/kg/day for 5 days) resulted in a 20-50% decrease in hepatic alanine aminotransferase (P < or = 0.05), a 10-20% decrease in aspartate aminotransferase (P < or = 0.04), and a 50 200% increase in alkaline phosphatase (P < or = 0.02). The activity of hepatic 5' nucleotidase was unchanged. In the serum, there was no significant change in the activity of any of the enzymes. Histologically, there was no damage detectable by light or electron microscopic examination of the liver, and no evidence of biliary obstruction. However, in frozen liver sections stained histochemically for alkaline phosphatase, there was a dramatic increase in the activity of this enzyme in hepatocytes, which was confined to the bile canaliculi. There was also a 3- to 9-fold increase in the mitotic activity of hepatocytes. Comparable changes have been reported in the tumor-free liver of animals with cancer. PMID- 8502662 TI - Exercise training improves cardiac performance in diabetic rats. AB - Diabetes mellitus is often associated with a cardiomyopathy characterized by alterations in cardiac metabolism and declines in cardiac performance. We sought to determine whether exercise training would attenuate the depressed cardiac performance seen in diabetic animals. Female rats were divided into four groups: sedentary control, trained control, sedentary diabetics, and trained diabetics. After 1 week of training, we induced diabetes by intravenous injection of streptozotocin (65 mg/kg). We trained animals on a treadmill using a progressive protocol that plateaued at 27 m/min for 1 hr/day, 5 days/week for a total of 8 weeks. We measured cardiac output at a variety of left atrial filling pressures with an isolated working heart apparatus; glucose was the sole metabolic substrate for the heart. Training increased succinate dehydrogenase activity in the soleus muscle of exercised rats, but did not change heart and body weights or plasma glucose and thyroid hormone levels. The diabetic groups exhibited depressed cardiac outputs at high workloads compared to nondiabetics. Training increased the cardiac output of both sedentary and diabetic animals at high, but not low, preloads. We suggest that exercise can attenuate the severity of diabetic cardiomyopathy. PMID- 8502663 TI - Comparative responses of rats to different copper intakes and modes of supplementation. AB - Purified diets deficient in copper and based on either sucrose, egg white, and corn oil or sucrose, casein, corn starch, and safflower oil were fed to young rats. Graded amounts of copper were supplied in drinking solutions with the former diet and by addition to the latter diet; anatomical, chemical, and physiologic responses were compared. Three micrograms Cu/ml and 5 micrograms Cu/g were sufficient to maximize the direct assessments of copper nutriture (copper in blood plasma, heart, and liver). Nutritional adequacy by indirect criteria (heart iron, plasma ceruloplasmin, heart weight divided by body weight, plasma cholesterol, and body weight) generally was found with 3 micrograms/ml and 4 micrograms/g. Anemia was an insensitive characteristic of deficiency. Liver iron was minimized by 4 micrograms Cu/ml and 5 micrograms Cu/g. Most of the differences in response to copper added to water in comparison to copper added to diet probably were explained by the lower amount of copper in the casein diet. Responses to the two dietary regimens were similar when variables were plotted against liver copper. Correlation coefficients with liver copper ranged from 0.52 for liver zinc to 0.96 for heart iron. Liver copper probably is the best index of copper nutriture. PMID- 8502665 TI - Short-term ingestion of a high protein diet increases liver and kidney mass and protein accretion but not cellularity in young pigs. AB - Increased visceral organ mass raises the energy cost of maintenance in animals. To determine the nutritional factors that affect organ size during growth and development, we studied 12 genetically obese 4-week-old pigs for 14 days. The piglets had free access to either a control (17% protein) or a high protein (34%) diet. They were sacrificed after 14 days and their empty gastrointestinal tracts, livers, and kidneys were weighed and samples were analyzed for protein and DNA concentrations. The absolute and relative (percentage of body weight) weights of liver and kidneys were greater in high protein than control piglets: liver (313 vs 246 g, SD = 24, P < 0.09; 3.61% vs 3.18%, SD = 0.04, P < 0.01); kidneys (57 vs 41 g, SD = 4, P < 0.04; 0.66% vs 0.55%, SD = 0.02, P < 0.01). Protein content was greater in high protein than control pigs in both liver (48.2 vs 34.0 g, SD = 3.4, P < 0.03) and kidneys (6.0 vs 4.6 g, SD = 0.5, P < 0.06). Liver and kidney total DNA were unaffected by diet in both groups. The protein to DNA ratio was greater in high protein than control pigs in both liver (45.4 vs 39.0, SD = 0.6, P < 0.01) and kidneys (26.6 vs 24.9, SD = 0.4, P < 0.02). We conclude that when weaned pigs have free access to a high protein diet (2 x requirement) for 2 weeks, liver and kidney protein accretion increases, suggesting cell hypertrophy, with no clear evidence of cell hyperplasia. PMID- 8502664 TI - Regulation of kininogen gene expression and localization in the lung after monocrotaline-induced pulmonary hypertension in rats. AB - Pyrrolizidine monocrotaline (MCT) from plant seed produces pulmonary endothelial cell injury, pulmonary hypertension, and inflammation in rats, providing a useful animal model for studying progressive pulmonary vascular disease. Kininogen is the precursor of proinflammatory kinins and may also exert anti-inflammatory actions by inhibiting cysteine proteinases. Given the potential roles of kininogen in vascular injury and inflammation, we have investigated the regulation of kininogen gene expression in the MCT-induced pulmonary hypertensive rat model. Sprague-Dawley rats, in groups of six, were given a single subcutaneous injection of monocrotatine (60 mg/kg body wt) and sacrificed 10 and 20 days later. Northern blot hybridization using a kininogen cDNA probe showed kininogen gene expression in the liver, lung, and kidney. MCT treatment induced a time-dependent increase in kininogen mRNA levels, whereas it reduced rat alpha 1 antitrypsin and kallikrein-binding protein mRNA levels in the liver. Similarly, kininogen mRNA levels were low in the normal lung and were increased 7.5- and 13.7-fold, respectively, after MCT injection for 10 and 20 days. Immunoreactive kininogen levels in perfused liver and lung extracts of rats receiving MCT injection increased up to 20-fold, as measured by a T-kininogen radioimmunoassay. Western blot analyses showed that a 68-kilodalton immunoreactive kininogen increased in the serum and lung extracts of MCT-treated rats compared to those in the control rats. In control rats, immunostaining for kininogen in the lung was most marked in venous endothelial cells and alveolar macrophages. After MCT treatment, staining for kininogen increased dramatically throughout the lung tissues, often covering the epithelial surfaces of alveoli and bronchi. The present studies have shown that the toxin MCT altered the synthesis and distribution of pulmonary kininogen and suggest that the kininogen/kinin system may be associated with the pulmonary vascular injury, remodeling, and inflammation seen in this animal model. PMID- 8502666 TI - Introduction to HDV genome replication. PMID- 8502667 TI - Hepatitis delta virus-like agents: an overview. PMID- 8502668 TI - Hepatitis delta virus pathogenicity. AB - This review has presented data consistent with the hypothesis that HDV may be directly cytopathic or non-cytopathic depending on the stage of infection. Nevertheless, although a majority of HDV-infected patients show evidence of liver disease, healthy carriers of the virus lead to the suggestion that different healthy carriers of HDV can exist, but particularly in the absence of a florid HBV replication. These results lead to the suggestion that different strains of HDV may result in different disease outcomes. Furthermore, the role of HBV in the pathogenetic process is unlikely to be passive, and some effort should be made to examine carefully the effects of the interplay between HBV variants and HDV and the course and pathogenicity of HDV infection (see Brunetto, this volume). PMID- 8502669 TI - Identification of promoters of hepatitis delta virus RNA transcription on hepatitis delta virus cDNA. PMID- 8502670 TI - Differential roles for HDAg-p24 and -p27 in HDV pathogenesis. PMID- 8502671 TI - Comparison of the presence of two forms of delta antigen in liver tissues of acute versus chronic delta hepatitis. PMID- 8502672 TI - Emergence of the long form of hepatitis delta virus antigen in transfected cells after intrahepatic transfection and during natural infection. PMID- 8502673 TI - Characterization of stable hepatitis delta expressing hepatoma cell lines: effect of HDAg on cell growth. PMID- 8502674 TI - Pathobiology of hepatitis delta virus infection at the cell level. PMID- 8502675 TI - Replication of HDV in the mouse. PMID- 8502676 TI - c-myc expression in cells infected with hepatitis delta virus. PMID- 8502677 TI - Modulation of hepatitis delta virus infection by vaccination with synthetic peptides: a preliminary study in the woodchuck model. PMID- 8502678 TI - Rabbit-derived anti-HD antibodies for HDAg immunoblotting. PMID- 8502679 TI - Immunisation of woodchucks with hepatitis delta antigen expressed by recombinant vaccinia and baculoviruses, controls HDV superinfection. AB - We report the investigation of the role of humoral and cell mediated immune responses on hepatitis delta virus (HDV) superinfection of woodchucks chronically infected with woodchuck hepatitis virus (WHV). The animals were immunised with baculovirus or vaccinia virus recombinant hepatitis delta antigen (HDAg) but none showed detectable anti-HD titres prior to challenge with HDV. Following infection, both immunised and control animals developed HD-antigenaemia first detected after 2-3 weeks and lasting for up to 8 weeks. In spite of the presence of HDAg, in immunised animals HDV-RNA could only be detected by nested PCR in contrast with the controls, which were positive by dot blot hybridisation. No serum HDAg or HDV-RNA was detected after the acute episode over the six month follow-up period but intrahepatic HDAg was reported in post-mortem biopsies carried out at six months. Our results demonstrate that immunisation of woodchucks with HDAg expressed by vaccinia or baculovirus does not elicit a humoral immune response. The finding of a marked antigenaemia in the absence of serum HDV-RNA indicates a significant reduction in the number of circulating infectious virions possibly due to a cytotoxic T-cell response. PMID- 8502680 TI - The effects of using recombinant vaccinia viruses expressing either large or small HDAg to protect woodchuck hepadnavirus carriers from HDV superinfection. AB - Live rVVs expressing either p24 delta or p27 delta were produced and used to immunize woodchuck hepadnavirus carriers. Upon challenge with infectious HDV, circulating HDV RNA levels appeared to be similar in both controls and vaccinees. Although extended follow-up studies of these animals is necessary before making firm conclusions, including an analysis of circulating HDAg levels, these preliminary results provide no evidence for a protective immunity conferred by the rVVs. In contrast, we have shown in other studies that repeated immunization of woodchucks with purified, recombinant p24 delta subunit does confer significant protection against HDV challenge in some of the vaccinees (A. Ponzetto, et al., this volume). The underlying immunological mechanisms responsible for the different outcome of these varied vaccination regimens remain to be elucidated. PMID- 8502681 TI - Towards a vaccine for the prevention of hepatitis delta virus superinfection in HBV carriers. PMID- 8502682 TI - Functional domains of hepatitis delta antigen. PMID- 8502683 TI - Introduction to interactions between hepatitis viruses. PMID- 8502684 TI - Relations between hepatitis delta virus pathogenicity and hepatitis B virus heterogeneity. PMID- 8502685 TI - Acute delta hepatitis in Greek parenteral drug abusers. PMID- 8502686 TI - Suppression of hepatitis delta virus by concurrent hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. PMID- 8502687 TI - Prevalence of wildtype and pre-C HBV variants in HBsAg/anti-HBe positive carriers with chronic hepatitis delta virus infection. PMID- 8502688 TI - Delta hepatitis and infection in North America. PMID- 8502689 TI - An overview of hepatitis D virus infection in Africa and the Middle East. PMID- 8502690 TI - Changing epidemiology and spreading modalities of hepatitis delta virus infection in Greece. PMID- 8502691 TI - Seroprevalence of HDV and HIV in two populations at risk for infection with HBV in Spain. AB - We have studied 1765 patients attending our clinic during 1991, with the aim of determining the prevalence of HDV and HIV infection in our country in two populations at risk for parenteral and sexual HBV transmission. A second objective was to determine whether or not HBV-HIV co-infection was associated with a greater risk for HDV. Our findings indicated that sexual transmission of VHD is not common, unlike parenteral transmission, and that there is a significantly greater prevalence of infection with HDV in Chi-square who have the HBsAg complex and are HIV positive. PMID- 8502692 TI - HDV infection in Cyprus. PMID- 8502693 TI - The epidemiology of hepatitis delta infection in Italy over the last 18 years. PMID- 8502694 TI - Hepatitis B surface antigen and large-form hepatitis delta antigen in HDV assembly: a further study. PMID- 8502695 TI - The natural history of chronic HDV infection. PMID- 8502696 TI - Prognostic significance of IgM anti-HD during interferon therapy. PMID- 8502697 TI - Serological diagnosis of chronic delta infection: correlation between serological markers and hepatitis delta virus RNA in hepatic tissue. PMID- 8502698 TI - New diagnostic assays for the detection of HDV-RNA and HDV-antibodies. PMID- 8502699 TI - Polymerase chain reaction-based detection of hepatitis D virus RNA in patients infected with human immunodeficiency virus. AB - We used the polymerase chain reaction (PCR) to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients were prospectively found to be infected by HDV. Thirty-one anti HIV-positive patients were studied by means of PCR and the results were analysed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in five patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and three were HBV-DNA positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairement in HDV-PCR positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was only evidenced in HDV infected patients in whom 5/19 were positive. This test allowed direct diagnosis of HDV viremia and will be useful for the monitoring of HDV infection. PMID- 8502700 TI - Therapy of chronic delta hepatitis: overview. PMID- 8502701 TI - Therapy of chronic delta hepatitis with alpha- and beta-interferon. PMID- 8502703 TI - Italian trials of interferon alpha in chronic delta hepatitis. PMID- 8502702 TI - Structure and function of the delta virus antigens. PMID- 8502704 TI - Lymphoblastoid interferon in patients with chronic nAnB hepatitis showing relapse during recombinant alpha interferon therapy. PMID- 8502705 TI - Prolonged alpha interferon therapy for chronic delta hepatitis: effect on liver histopathology. AB - Alpha interferon therapy in patients with chronic delta hepatitis treatment was associated with a decrease in serum aminotransferase activities and disappearance or decrease in serum levels of HDV RNA. Serum biochemical and serological changes were associated with amelioration of hepatic injury and a decrease (but not a disappearance) in hepatic HDAg on liver biopsy. Two cases lost HBsAg during therapy, only one of whom had lost hepatic HDAg entirely at the end of therapy. Interestingly, a decrease in HDV replication was associated with an apparent increase in HBV replication in some cases. PMID- 8502706 TI - Modified HDV as a vector for the delivery of biologically-active RNAs. PMID- 8502707 TI - Liver transplantation for viral hepatitis: the current situation. PMID- 8502708 TI - Liver transplantation for patients with hepatitis delta infection. PMID- 8502709 TI - Different aspects of HDV and HBV reinfections and liver disease in orthotopic liver transplant (OLT). PMID- 8502710 TI - Recurrence of HDV infection after liver transplantation. PMID- 8502711 TI - Patterns of hepatitis delta reinfection after liver transplantation and their evolution during a long term follow-up. PMID- 8502713 TI - Hepatitis delta virus disease: an overview. PMID- 8502712 TI - Histopathology of recurrent delta hepatitis in liver transplant. PMID- 8502714 TI - Hepatitis delta virus and the host response: current status and future perspectives. AB - The demonstration that recombinant vaccinia can control the level of viraemia after HDV superinfection raises the possibility that established HBV carriers can be immunized against HDV. Furthermore the likelihood that this protective effect is dependent on the induction of a CTL response to HDV raises the possibility that the therapeutic effect of interferon operates by the induction of this cellular response. The failure of interferon to exert a direct inhibitory effect on HDV replication needs further investigation as does the nature of the immune responses involved in the protective effect induced by immunization with recombinant vaccinia. PMID- 8502715 TI - Analysis of hepatitis B virus envelope proteins in assembly and infectivity of human hepatitis delta virus. PMID- 8502716 TI - Determinants of RNA editing in hepatitis delta virus. PMID- 8502717 TI - Novel targets of anti-hepatitis delta virus therapy. PMID- 8502718 TI - Dimeric and multimeric forms of hepatitis delta virus antigen are present in infected woodchuck liver. PMID- 8502719 TI - Experimental evidence for the secondary structure of the hepatitis delta virus ribozyme. AB - Specific features of a model for the secondary structure of the self-cleaving RNA sequences (ribozymes) of hepatitis delta virus were rigorously tested. Using a self-cleaving form of the antigenomic sequence, mutations were made in the 5' and 3' sequences of each of four duplex regions within the proposed ribozyme structure. Precursor RNA from each variant sequence was prepared and the kinetics of cleavage in 10 mM Mg2+ at 37 degrees was examined. The data was quantified to determine an end point and a first-order rate constant for cleavage with each mutant by fitting the data to the exponential form of the first-order rate equation. With regard to the final extent of cleavage, most mutations in these regions appeared to have little effect, however, the kinetics indicated that disruption of the potential for basepairing resulted in dramatic decreases in the rate constant for cleavage. These results are consistent with the idea that most of the mutations affected ribozyme activity rather than an equilibrium between precursor and cleavage products. Mutations that reduced rates were compensated by changes that restored the potential for Watson-Crick pairing. Ribonuclease probing of ribozyme variants containing mismatches and compensatory changes allowed direct correlation of structural changes with the mutations. This provided an independent validation of the functional kinetic assay. Thus, site directed mutagenesis was consistent with a proposed ribozyme secondary structure containing 4 distinct base-paired regions. PMID- 8502720 TI - Self-cleavage of internally deleted hepatitis delta RNAs. PMID- 8502721 TI - Trans cleavage of RNA substrates by an HDV-derived ribozyme. PMID- 8502722 TI - The major intrinsic light-harvesting protein of Amphidinium: characterization and relation to other light-harvesting proteins. AB - A major light-harvesting complex (LHC) has been obtained from thylakoids of Amphidinium carterae solubilized with digitonin or decylmaltoside and separated by sucrose-gradient centrifugation. The digitonin-LHC forms a dark brown band at approximately 17% sucrose and the decylmaltoside LHC one at approximately 7% sucrose. Excellent energy transfer is retained from chlorophyll c and carotenoid to chlorophyll a. Absorbance and fluorescence excitation spectra show the existence of two major forms of chlorophyll c, one absorbing at 634 nm and the other at 649 nm. Linear dichroism spectra show the Qy transition of both forms of chlorophyll c to be aligned at < 35 degrees to the membrane plane. On sodium dodecylsulfate polyacrylamide gels the complex resolves as a single band of 19 kDa. A partial amino acid sequence shows the N-terminus to be unblocked but modified; there is a persistent ambiguity of Ser/Asn at residue 4 and evidence for multiple but very similar polypeptides within the 19 kDa band. The peptide has strong identity with the N-terminal regions of LHC from Phaeodactylum and Pavlova and LHC 1 of higher plants. Antibodies to the 19 kDa peptide react weakly with LHC of brown algae, diatoms and Prymnesiophytes but not with those of higher plants or Cryptophytes. PMID- 8502723 TI - Pigment complexes of light-harvesting chlorophyll a/b binding protein are stabilized by a segment in the carboxyterminal hydrophilic domain of the protein. AB - In order to identify segments of light-harvesting chlorophyll a/b-binding protein (LHCP) that are important for pigment binding, we have tested various LHCP mutants regarding their ability to form stable pigment-protein complexes in an in vitro reconstitution assay. Deletion of 10 C-terminal amino acids in the LHCP precursor, pLHCP, did not significantly affect pigment binding, whereas deletion of one additional amino acid, a tryptophan, completely abolished the formation of stable pigment-protein complexes. This tryptophan, however, can be exchanged with other amino acids in full-length pLHCP without noticeably altering the stability or spectroscopic properties of pigment complexes made with these mutants. Thus, the tryptophan residue is not likely to be involved in a highly specific interaction stabilizing the complex. A double mutant of LHCP lacking 66 N terminal and 6 C-terminal amino acids still forms pigmented complexes that are virtually identical to those formed with the full-length protein concerning their pigment composition and spectroscopic properties. We conclude that about 30% of the polypeptide chain in LHCP is not involved in pigment binding. PMID- 8502725 TI - Carotenoid-to-bacteriochlorophyll singlet energy transfer in carotenoid incorporated B850 light-harvesting complexes of Rhodobacter sphaeroides R-26.1. AB - Four carotenoids, 3,4,7,8-tetrahydrospheroidene, 3,4,5,6-tetrahydrospheroidene, 3,4-dihydrospheroidene and spheroidene, have been incorporated into the B850 light-harvesting complex of the carotenoidless mutant, photosynthetic bacterium, Rhodobacter sphaeroides R-26.1. The extent of pi-electron conjugation in these molecules increases from 7 to 10 carbon-carbon double bonds. Carotenoid-to bacteriochlorophyll singlet state energy transfer efficiencies were measured using steady-state fluorescence excitation spectroscopy to be 54 +/- 2%, 66 +/- 4%, 71 +/- 6% and 56 +/- 3% for the carotenoid series. These results are discussed with respect to the position of the energy levels and the magnitude of spectral overlap between the S1 (2(1)Ag) state emission from the isolated carotenoids and the bacteriochlorophyll absorption of the native complex. These studies provide a systematic approach to exploring the effect of excited state energies, spectral overlap and excited state lifetimes on the efficiencies of carotenoid-to-bacteriochlorophyll singlet energy transfer in photosynthetic systems. PMID- 8502724 TI - The role of redox-active amino acids in the photosynthetic water-oxidizing complex. AB - The protein environment can dramatically affect the EPR line shape of tyrosine radicals. The alterations can be caused by: (1) a change in methylene geometry caused by different protein steric constraints; (2) a change in spin density caused by a change in protein environment; or (3) covalent modification of the tyrosine. Any or all of these effects may also be important, in some cases, in control of oxidation potential and chemical reactivity. The new signal that has been observed in the YF161D1 PS II mutant has an approximate 1:3:3:1 lineshape. There is no precedent for a 1:3:3:1 EPR signal from a tyrosine in a powder sample. However, as described above, given the diversity of signals from tyrosine radicals, it is impossible to exclude the possibility that the signal arises from tyrosine on this basis. PMID- 8502726 TI - A contribution to the analysis of the psychoanalytic process. AB - The place of analyst-patient interactions in the psychoanalytic change process is much debated. This paper reflects an attempt to identify quite specific relational impacts that flow from the requirements of the psychoanalytic situation itself and are (a) essential to the psychoanalytic process, (b) inseparably tied to interpretation, and (c) of quite broad significance. Relationship factors that are idiosyncratic, iatrogenic, or that involve a nonspecific benign tone are all discussed by way of contrast to features seen as essential to the interpretive process. The published literature is heavily used to develop these points. PMID- 8502727 TI - On the sense of absence: a perspective on womanly issues. AB - Many women express complaints about their mental capacities which are discordant with objective indicators of superior intelligence and functioning. They find their memories unreliable, for example, despite intense efforts to retain facts or ideas. Using clinical material, the author attempts to elucidate how psychic representation of the vagina can contribute to a sense of mental defectiveness, experienced by certain women as peculiarly feminine. The role of such a psychic representation tends to go unrecognized, given that the female genital is usually conceptualized as an "absence" rather than a presence in its own right. PMID- 8502728 TI - On hate in love relationships: the narcissism of minor differences revisited. AB - Among the many reasons that feelings of hate develop in love relationships is the need to find and to exaggerate differences in order to maintain a sense of separateness. Freud's notion of the "narcissism of minor differences" provides a framework within which to understand this need to find disappointing differences in one's beloved. Developmental antecedents of this concern about defining and preserving one's separateness can be identified in both oedipal and preoedipal periods. PMID- 8502729 TI - Creativity: a work in progress. AB - Through the integration of autobiographical, theoretical, and clinical material, the author attempts to describe a developmental path leading to a "creative" solution to object loss. The implications of this model are considered both for the particular type of individual described and for general psychoanalytic theory and technique. PMID- 8502730 TI - The use of an audiotaped analysis in a continuous case seminar. AB - The use of an audiotaped analysis in a continuous case seminar is evaluated. We compare this case seminar to the traditional one in which an analyst presents process notes, and find that the use of the tape lends itself readily to teaching microanalysis, principles of technique, and observation of affect. Listening to anonymous taped sessions allowed for the possibility of a freer climate for discussion, as none of the seminar participants had a personal relationship with the taped analyst. The disadvantages posed by the absence of the analyst during the seminar also are addressed. PMID- 8502731 TI - "Bright spot," a variant of "blind spot". PMID- 8502732 TI - Infant observation and psychoanalytic theory. PMID- 8502733 TI - [A rise in the incidence of teratological changes in Plantago lanceolata L. seedlings of the 5th post-accident reproduction in the 30-kilometer area of the Chernobyl Atomic Electric Power Station]. AB - It was for the first time that of the fifth year of monitoring of Plantago lanceolata L., reproduced within the thirty-kilometer zone of Chernobyl NPP disaster, the authors discovered high incidence of seedlings with various morphological abnormalities. It is suggested that the damages observed are related to the cumulative effect of radiation. PMID- 8502734 TI - [DNA apurinization and apyrimidinization of gamma-irradiated silkworm embryos at different developmental stages]. AB - A study was made of the formation and repair of apurine-apyrimidine (AP) sites in DNA of gamma-irradiated 3- and 7-day embryos of Bombyx mori differing drastically in radiosensitivity. The number of AP-sites in DNA immediately after irradiation was much larger in DNA of 3-day embryos than in DNA of 7-day embryos. The kinetics of the postirradiation recovery of AP sites in DNA of 3- and 7-day Bombyx mori embryos was heterogeneous and varied significantly. PMID- 8502735 TI - [Changes in chromatin conformation induced by ionizing radiations with different LETs in resting and proliferating hepatocytes from rats of different ages]. AB - The method of flow cytometry was used to study conformation changes in rat hepatocyte chromatin exposed to various doses of X-rays and fission neutrons (mean energy of 0.85 MeV). Chromatin decondensation induces by both X-rays and neutrons was shown to be a function of dose. The saturation effect was observed for X-rays doses ranging from 4 to 6 Gy; for fission neutrons no saturation effect was noted within the dose range from 0.5 to 4 Gy. The initial chromatin level, that changed during the cell cycle and upon ageing, influence induction of conformation changes in the chromatin. The authors discuss the dependence of the processes of repair and fixation of damages to hereditary cell structure on the chromatin conformation at the time of exposure. PMID- 8502736 TI - [Patterns in the distribution of chromosome aberrations in the cells of hydrobionts under the action of ionizing radiation and environmental chemical mutagens]. AB - In studying the pattern of chromosome aberration distribution among hydrobiont cells in experimental and natural populations, it has been found that the Poisson distribution of chromosomes among cells occurs under the effect of ionizing radiation and under the combined effect of radiation and a chemical mutagen with a higher efficiency of the former. With the comparable efficiencies of both factors and with the effect of a chemical mutagen alone distribution of chromosome aberrations among cells resembles the geometrical one to a greater extent. PMID- 8502737 TI - [The effect of gamma irradiation on the proliferative activity of the cambial epithelium in a culture of thymus stromal cells]. AB - A study was made of the effect of gamma radiation on proliferation of thymus stroma epithelial cells (EC) of newborn mice (CBA x C57Bl/6)P1 where EC content varied from 55% to 85%. EC proliferation was assessed 24 and 48 h after gamma irradiation by studying the mitotic activity of thymus EC and rate of MTT recovery (which permitted us to determine the nature of proliferating cells by their morphology). The quantitative characteristics of the two methods were identical. The effect of gamma radiation was assessed at various cultivation times. Irradiation at the time of inoculation reduced the proliferation of cells to logarithmic phase of growth. Irradiation with doses of 10 and 20 Gy after two day cultivation inhibited proliferation of thymus EC and with 15 Gy increased the proliferative activity of thymus epithelium. PMID- 8502738 TI - [The effect of intracellular pH on radiation damage to mammalian cells]. AB - In experiments with Chinese hamster cells and Ehrlich ascites tumor cells it has been shown that a decrease in intracellular pH from 7.0 to 6.0, produced by 0.1 M phosphate buffer, ameliorates the radiation injury to cells (DMF = 1.35) with respect to their clonogenic capacity and induction of chromosome aberrations. The rate of repair of DNA single-strand breaks, within the pH range under study, is invariable. PMID- 8502739 TI - [The effect of ionizing radiation on the resistance of rat pancreatic beta cells to streptozotocin]. AB - The effect of subliminal streptozotocin doses of rat pancreas cells was studied 1 and 3 months after 1-Gy gamma irradiation. Streptozotocin injected to irradiated animals caused a drastic decrease in beta-cell function which was manifested by hyperglycemia and less intensive secretion and lesser content of insulin in isolated pancreatic islands, as compared to control. PMID- 8502740 TI - [The formation and viability of hybrid cells in a population after irradiation at lethal doses]. AB - With the use of two genetically labeled lines of Djungarian hamster cells and the method of hybrid selection on a HAT-selective medium it was found that in the irradiated mixed culture of the above cell lines, cells were formed that survived in the conditions of total destruction of irradiated parent cells. The chromosome analysis showed that about 45% of the survived cells were hybrids resulting from the radiation-induced fusion of two initial cell lines. These hybrid cells were capable of reproduction. A subline of hybrid cells was isolated. It is assumed that the radiation-induced process of cell fusion and the formation of viable somatic hybrids might be essential for the survival of cell population in the course of tumor radiotherapy. PMID- 8502741 TI - [The capacity of rat clonogenic precursor cells of the hemopoietic stroma (CFU-F) to recover from radiation damages]. AB - The ability of cell precursors of the haemopoietic stroma (CFU-F), that are present in the bone marrow of adult rats, to recover from potentially lethal and sublethal radiation damages has been investigated. The highest reparability, with respect to potentially lethal damages, is displayed by the most radioresistant CFU-F population, that forms loose colonies (clones) in a culture; the slope of the dose-response curve, not the extrapolation number, changes, and heterogeneity of the CFU-F population is observed. The results obtained confirm the presence of heterogeneity in the population of CFU-F, that was revealed in studying their radiosensitivity by the formation of dense and loose fibroblast colonies in a culture. PMID- 8502742 TI - [The effect of the gas hypoxic mixture GHM-8 on the capacity of the stromal clonogenic cells (CFU-F) in rat bone marrow for postradiation recovery]. AB - The effect of gas hypoxic mixture, containing 8% of O2 (GHM-8), on the ability of cell precursors of haemopoietic stroma (which form colonies (clones) of fibroblasts (CFU-F) in a culture, and are present in the bone marrow of adult rats) to repair potentially lethal and sublethal radiation damages has been investigated. The recovery of CFU-F from potentially lethal damages, that was studied after their delayed survival in a culture following irradiation of animals, proceeds at nearly the same rate in cells irradiated both in the air and in hypoxic conditions (GHM-8). Fractionated irradiation reduces the radioprotective effect of GHM-8 for CFU-F, particularly for the radioresistant subpopulation; the ability of CFU-F to recover from sublethal radiation damages decreases. PMID- 8502743 TI - [The individual glycolysis enzymes in the enterocytes of the rat small intestine studied during exposure to ionizing radiation]. AB - Activity and isoenzyme composition of certain enzymes of glycolysis of rat small intestine enterocytes was studied in the course of exposure to X radiation. Hexokinase activity was shown to increase significantly throughout the entire period of observation. Activity of pyruvate kinase and lactate dehydrogenase was inhibited at early (days 1-3) and increased at later (days 5-10) times of observation. PMID- 8502744 TI - [A comparison of the efficacy of the anticlastogenic action of interferon and of the radiation-adaptive response]. AB - Human lymphocytes, in the in vitro culture, exposed to X-rays (0.05 Gy) or treated with lymphoblastoid interferon (50 IE/ml) in phase G1 were less susceptible to induction of chromosome aberrations, of a chromosome type, by subsequent gamma-radiation (2 Gy) than those exposed to 2 Gy radiation only. The anticlastogenic effect of the pretreatment with interferon was considerably higher than that of preirradiation with X-rays which might be the result of the pleiotropic action of interferon in a cell. PMID- 8502745 TI - [The dynamic behavioral characteristics of rats in a maze after isolated and combined exposures to ionizing radiation and psychoemotional stress]. AB - Rats exposed to ionizing radiation (0.5 Gy) and short-term immobilization stress displayed CNS activation accompanied by diminution of working memory when tested in radial maze. Irradiation, as compared to stress, caused exploratory activity inhibition that led to certain automatism in task fulfillment. Exposure to emotional stress after irradiation modified significantly rat performance causing CNS inhibition and long-term memory decline. PMID- 8502746 TI - [The characteristics of the development of bacterial enterotoxemia and endotoxemia in combined radiation and thermal lesions]. AB - Thermal burn of irradiated rats increases the level and the length of the postirradiation enteroendotoxemia and aggravates the postirradiation impairment of the hematoenterocitic barrier. The pharmacological correction of the small intestine motility and introduction of ciproheptadine, an agent that blocks serotonin receptors, ameliorates the above phenomenon in radiation and thermal injuries. PMID- 8502748 TI - [The antiradiation effectiveness of a mixture of Archangelica officinalis and Ledum palustre extracts in the fractionated gamma irradiation of mice]. AB - In experiments with mice a study was made of the favourable effect of a single dose of a mixture of extracts from Archangelica officinalis and Ledum palustre on the severity of radiation injury induced by fractionated gamma irradiation (doses of 1 and 4 Gy, cumulative dose of 12 Gy). Injection of the mixture prior to the first dose of 4 Gy (given 3 times at a 2-7 day interval) caused a significant decrease in the damaging effect with respect to both the survival rate and the average life expectancy of exposed mice. With fractionated irradiation, the protective effect of the extract mixture increased with decreasing efficiency of the cumulative radiation dose. The results obtained indicate that the mixture used protects the animals from the injury to both the gastrointestinal tract and the haemopoietic system. PMID- 8502747 TI - [The action of gamma irradiation on the luminol-dependent chemiluminescence of activated thymocytes]. AB - The method of luminol-dependent chemiluminescence was used to study the affect of gamma radiation on activation of cells of thymus and bursa of Fabricius upon their adhesion on kapron. Thymocyte activation by adhesion on glass or kapron provoked chemiluminescence which was connected with the development in cells of active oxygen forms. The chemiluminescence amplitude was shown to increase with adhesion of thymocytes exposed to 1-5 Gy radiation and to decrease after a dose of 10 Gy. In cells of bursa of Fabricius, the analogous response to activation or irradiation was not observed. PMID- 8502749 TI - [The antiradiation action of 6-methyluracil]. AB - A single dose of 6-methyluracil (50 mg/kg) administered intraperitoneally to BALB and SHK mice prior to X irradiation (5.0 Gy) produced a pronounced radioprotective effect which was dependent upon the initial antioxidant status of the body, but independent of the effect of the agent on postirradiation leukopenia dynamics. The radioprotective effect of 6-methyluracil was conditioned by its influence on lipid peroxidation regulation and was displayed by the normalization of the antioxidant activity of lipids of radiosensitive organs and tissues and by high activity of superoxide dismutase in the liver and erythrocytes. PMID- 8502750 TI - [A theoretical and experimental study of a modification in the processes of plutonium-239 metabolism in body tissue systems]. PMID- 8502751 TI - [The protective action of calcium alginate in chronic 90Sr uptake into the body]. AB - Strontium 90 was given to rats with the diet over a period of 3 months. Administration of a modified calcium alginate reduced 90Sr deposition in the skeleton by 70-90%. No changes in the digestive organs were observed throughout the above period. PMID- 8502752 TI - [The effect of incorporated cesium-137 on the structure of the erythrocyte membranes]. AB - The influence of incorporated cesium 137 (the absorbed doses of 0.26-0.08 Gy) on the erythrocyte membrane structure has been investigated. It has been shown that chronic internal exposure to gamma radiation causes structural reorganization of erythrocyte membranes at remote postirradiation times (in 3 and 6 months) that influences the annular membrane lipid. PMID- 8502753 TI - [Changes in the retinal structural elements in the early and late periods after neutron exposure]. AB - Local fractionated exposure of a rabbit eye to fast neutrons of 3 Gy (1.5 x 2) and 7.5 Gy (1.5 x 5) induces early reactions of all structural elements of retina, among which dose-dependent degradation of photoreceptor membrane discs and damages to pigmentoepitheliocytes are of prime importance. Further pathomorphogenesis is connected with the surpassing degeneration of a radial glia with respect to destruction of interneuronal synapses and a minor part of neurons. The postirradiation (one and six months after 7.5 Gy irradiation) changes in the blood-retinal barrier are responsible for the disturbances in the glioneuronal complex. PMID- 8502754 TI - Cholesterol metabolism and colon cancer. AB - While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3 methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use low density lipoprotein to support cellular growth, unlike normal fibroblasts. Diminished low density lipoprotein (LDL) receptor (LDL-R) activity is a significant alteration in a metabolic pathway with such fundamental ties to cellular growth and activation (via mevalonate effects on isoprenylation of G-proteins for example), that it is selected for in the development of certain tumors--among them human colonic carcinomas. It would be expected that such a loss would provide a growth advantage to the tumor cell. Preliminary investigation of this hypothesis has shown that LDL will inhibit the proliferative capacity of certain human colonic adenocarcinomas, and that these cells possess a high rate of cholesterol synthesis relative to fibroblasts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8502755 TI - Fat intake and immune response. AB - Changing the concentration or the type of fat intake impacts several aspects of the immune response involving lymphocytes, monocytes, and neutrophils. An increase in the intake of fat inhibited immune response in humans and in several animal models. Polyunsaturated fatty acids (PUFA) of N-6 type lowered immune response in several animal models, but a moderate increase in the consumption of N-6 PUFA by humans did not have any detectable adverse effect on the immune response. In humans, several indices of immune response were inhibited by the N-3 PUFA, but in animals both inhibition and stimulation were found, depending upon the species, the fatty acids used and the index being examined. Whether the absolute amounts or the ratios between individual fatty acids or fatty acid classes are critical in determining their effects on immune response need to be investigated. Manipulation of fat intake has already found limited success in managing some of the disorders of the immune system and further use of this treatment is anticipated. PMID- 8502756 TI - Nutritional implications of the interactions between minerals. AB - It is well recognized that the absorption, retention and metabolism of most essential minerals can be markedly influenced by the presence of antinutrient factors in the diet (i.e. fiber and phytate). However, in addition, interactions can also occur between essential minerals. Indeed, under some circumstances, these interactions can be profound and have significant implications for human health. Interactions between essential minerals can be broadly classified as direct or indirect. Direct interactions are generally competitive phenomena that occur during the intestinal absorption and/or during the tissue utilization of a mineral. Indirect interactions occur when one of the minerals is involved in the metabolism of the other mineral, or when a deficiency or toxicity of one of the minerals results in hormonal changes or tissue damage which affects the metabolism of the other mineral. In this review we have focused our comments on direct interactions between essential minerals, and we present suggested levels at which an excess of a mineral (coined "X") can significantly alter the metabolism of another mineral (coined "Y") for several of the known competitive interactions. This level is characterized as the lowest X/Y ratio of the dietary intakes which has been shown to produce negative consequences on the metabolism of the element Y (assuming the intake of Y is physiological). Moreover, the importance of the physiological status of the animal with regard to the determination of these ratios is discussed. The calculated X/Y ratio at which interactions may be predicted to occur is generally higher than the ratio calculated for most minerals using typical dietary intakes of X and Y in Western type diets. However, ratios which might be predicted to result in negative interactions do occur in select food products, and can be reached as a consequence of supplementation (either through food enrichment or therapeutic use of supplements). In fact, considering the ready availability of dietary supplements, such interactions may become commonplace. Finally, the interactions between essential and non-essential minerals (heavy metals) are briefly discussed, as are indirect mineral interactions. PMID- 8502757 TI - [What does "discomfort in current culture" mean today and what can it be called within the scope of critical political psychology?]. AB - Freud's "Civilization and its Discontents" (1930) serves the author as a point of departure for socio-psychological hypotheses that go beyond the biologistic bias of the late Freudian concept of drive and its approach to the subject in terms of the antagonism of eros and thantos and essay a concrete historical and social diagnosis of present-day "discontent" with our civilization. The view taken by Busch is indebted to the work of Klaus Horn and Alfred Lorenzer, regarding "discontent" as the result of a failed socialisation process of an internal nature, the expression of "damaged subjectivity". Like Freud before him, Busch speculates on the chances for the emergence of a "constitutional intolerance" not only towards war in the traditional sense but also towards the species of war that represents the major threat to mankind today: the technological and industrial warfare waged against the natural foundations of the very existence of homo sapiens on this planet. PMID- 8502758 TI - [Critique of the Freudian cultural concept]. AB - The author takes issue with Freud's understanding of civilization, pointing out that it is both functionalist and individualist and hence takes too narrow a perspective, the reason for this being, in the author's view, Freud's "methodological Hobbesianism". Freud operates on the assumption of drives that are both lower than and prior to the act of establishing civilization. Schmid Noerr contends, however, that as in the last resort Freud can only describe these in cultural/civilizational contexts, the conclusion must be that civilization is not only a normative standard placed over and against such drives but also a form of social organization of semiotic systems extending to the regulation of the emotional significantions incorporated in the drives themselves. PMID- 8502759 TI - [Patricide and the dialectics of enlightenment. The "fatherless society" as a model of psychoanalytic archaeology of modern times]. AB - Proceeding from Alexander Mitscherlich's socio-psychological diagnosis of the fatherless society (1963), the author goes back from there to Freud's "Totem and Taboo" (1912/13) and its treatment of the myth of the origins of culture. Heim reflects on the recurrent failure of culture, its constant relapse into murder and barbarism and sees this in connection with the dialectic nature of enlightenment, the patently intrinsic ambiguity of all progress achieved by homo sapiens. On the one hand, patricide and the advent of a fatherless society promise emancipation from mythic forces; on the other, latent feelings of guilt ensure that those forces remain operative and periodically explode into murderous activity. The fatherless society could only lose the terrors of ambivalence if it were possible to bring to an end the symbolism of the murdered father in the secularized equivalents of the totem, and to resolve the culturally seminal Oedipus complex of the primeval age in the conciliatory figures of post-Oedipal super-ego and ego-ideal. PMID- 8502760 TI - [Changes produce old ghosts anew--the insecure Europe]. AB - Since the fall of the Berlin Wall and the collapse of existing socialist dictatorships, some of the ghosts that we thought to have long since exorcised have returned to haunt us anew-aggressive forms of nationalism, which we have turned a blind eye to for decades, and a violent species of xenophobia on occasion openly homicidal in nature are prominent features of present-day European reality. In Beland's view, such alarming phenomena can only be controlled successfully if we can contrive-both on an individual and collective plan- to de-activate the psychic mechanism of projecting our own evils and flaws onto others (i.e. "foreigners") and to achieve what Melanie Klein calls the "depressive position", i.e. attain to a higher guilt tolerance. This, Beland contends, is the central utopia of European humanism. PMID- 8502761 TI - [Self-criticism and reconciliation capacity]. AB - With reference to empirical socio-psychological studies conducted by the author himself (on prejudices in connection with AIDS, inquiries into attitudes displayed by German and Russian students) and the results of opinion polls on xenophobia, racism and nationalism, the author demonstrates that reconciliation with oneself and others is proportional to the propensity for self-criticism and the ability to recognize and acknowledge personal guilt. Where, by contrast, self hatred and self-devaluation prevail, the tendency towards projection and hatred of others will also be dominant. PMID- 8502762 TI - Temporal variation in the effects of iced water on oral temperature. AB - The effect of iced water on the length of time required for oral temperature measurements to return to baseline in adults at 8:00 a.m. and 4:00 p.m. was examined. Each of the 24 subjects participated at both times of the day and thus served as his/her own control. Using electronic thermometers and standardized iced water solutions, the mean length of time required for oral temperature to return to baseline after ingestion of iced water was 14.04 min at 8:00 a.m. and 10.25 min at 4:00 p.m. This difference was statistically significant, supporting the hypothesized temporal variation in the effects of iced water on oral temperature measurement. PMID- 8502763 TI - Cerebral palsy: evaluation of a model of risk. AB - The purpose of this study was to assess a model of risk for cerebral palsy (CP) in preschool children. The research was structured as a retrospective case control study in which cases (n = 112) were children with CP while controls (n = 153) were either friend referrals or population-based. Data were collected via structured telephone interviews. While significant associations with CP were found on univariate analyses for a number of variables, only four variables- birth weight/gestational age, 5-min APGAR, medication for miscarriage, and urinary tract infection during pregnancy--were found predictive in multivariate analysis. These variables accounted for 36% of the log-likelihood explained by the model. PMID- 8502764 TI - The relationship between physical health and psychological well-being in elderly women: a developmental perspective. AB - Little is known about the physical health and psychological well-being of very old women, although they are one of the fastest growing segments of the population. The relationships among physical health, psychological well-being, and age were investigated using a developmental perspective and a multidimensional approach to the assessment of psychological well-being. Two hundred and forty-three elderly women completed multiple self-report measures of physical health status and psychological well-being. Multiple regression analyses indicated that older age was related to lower levels of purpose in life, personal growth, and positive relationships. Poor health, regardless of age, was associated with more depression and anxiety and lower levels of positive relationships and autonomy. Implications for the nursing care of elderly women are discussed. PMID- 8502765 TI - Relationships among selected antecedent variables and coping effectiveness in postmyocardial infarction patients. AB - Selected theoretical relationships from Lazarus' (1966) model of stress were tested in a convenience sample of 81 postmyocardial infarction clients. Two hypothesized causal models were analyzed. Results from regression analyses indicated 63% of the variance in coping effectiveness was explained by marital status, length of time since hospitalization, perceived availability of social support, uncertainty, degree of threat, coping strategies, and emotions. A revised model that fit the data was proposed. Findings indicated that emotions were an outcome of threat, not coping; threat did not directly affect coping strategies; and coping strategies did not directly influence coping effectiveness. PMID- 8502766 TI - Maternal confidence for labor: development of the Childbirth Self-Efficacy Inventory. AB - The Childbirth Self-Efficacy Inventory (CBSEI) is a self-report instrument that measures outcome expectancies and self-efficacy expectancies for coping with an approaching childbirth experience. The CBSEI scales have excellent internal consistency reliability (.86 to .96) and factor analysis suggested that each CBSEI scale is unidimensional. Validity of the CBSEI was supported by significant positive correlations with the criterion variables of generalized self-efficacy, self-esteem, and internal health locus of control; and significant negative correlations with external health locus of control and learned helplessness. Validity was also supported by significantly higher self-efficacy scores for multiparous as compared to nulliparous pregnant women. PMID- 8502767 TI - Guidelines for using psychometric consultants in nursing studies. AB - Consultation for measurement issues is an increasingly common expectation for many studies, yet there are few published guidelines on the use of psychometric consultants. The role of the psychometrician as research consultant is discussed and questions commonly asked of these measurement experts are identified. Consultation when selecting, revising, and developing data collection instruments is explored. PMID- 8502768 TI - Re: Attentional fatigue. PMID- 8502769 TI - A lingering identity crisis. PMID- 8502770 TI - The role of support surfaces and patient attributes in preventing pressure ulcers in elderly patients. AB - Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers, but there is little information about the effectiveness of different support surfaces. This randomized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer. Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers. Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface. PMID- 8502771 TI - Psychosocial predictors of consumption of sweets following smoking cessation. AB - The use of a theoretical model to predict consumption of sweet-tasting high calorie foods following smoking cessation was investigated. The model included eight predictors: habit, intention, attitudes, subjective norms, self-efficacy, perceived barriers, social support, and smoking cessation. One hundred and fourteen individuals completed pre- and post-questionnaires and made pre- and post-snack choices at smoking cessation programs. Pretest consumption of sweets (habit), pretest intention to avoid eating sweets, and posttest smoking status explained 42% of posttest consumption of sweets. Ex-smokers reported eating more sweets and chose more sweet snacks than did subjects who continued to smoke. PMID- 8502772 TI - Host factors in the pathogenesis of arthritis triggered by infectious organisms. Overview. AB - Individual variability in host immune responses to infectious agents is likely influenced by differences in the repertoires of antigenic peptides bound by self major histocompatibility complex molecules (MHC) and in the repertoires of T-cell receptors expressed in each individual. Moreover, genes regulating the processing of foreign MHC antigens (for example, peptide pump genes and proteosome constituent genes) may also be important in this regard. Infectious organisms may subvert host immune responses through expression of constituents sharing structure homology with host molecules. Such structural mimicry may serve to either promote induction of potentially harmful cross-reactive autoimmune responses or impede effective host responses, thereby favoring persistence of the organism. PMID- 8502773 TI - Soft tissue infections. AB - Several infectious processes ranging in severity from mild to overwhelming that affect the soft tissues are reviewed. Superficial infections such as impetigo, erysipelas, cellulitis, and subcutaneous bursitis are common and, for the most part, can be easily treated. Because suppurative tenosynovitis has the potential to destroy tendons, consultation with a hand surgeon should be obtained immediately. Mycobacterial and fungal tenosynovitis is usually chronic and patients present with a mass which, when excised and examined with appropriate stain and culture, reveals the unexpected diagnosis. Tropical myositis (muscle abscesses) is seen in temperate climates, primarily as a complication of AIDS. Necrotizing fasciitis and gas gangrene represent the hyperacute end of the spectrum of soft tissue restrictions. Although in most cases a history of trauma is present, spontaneous gas gangrene may arise from occult and colonic cancer. Patients do poorly unless immediate and extensive surgery is performed and appropriate antibiotics are given. PMID- 8502774 TI - Nongonococcal bacterial arthritis. AB - The most salient features of nongonococcal bacterial arthritis are reviewed. Factors such as life expectancy, prosthetic joints, arthroscopies, the spread of the AIDS epidemic, and of methicillin-resistant Staphylococcus aureus as modifiers of the course of these arthritides are discussed. PMID- 8502775 TI - Acute rheumatic fever. AB - The diagnosis of acute rheumatic fever has become difficult. A growing number of diseases that were not recognized in the past could fulfill its diagnostic criteria. We emphasize its changing incidence, current knowledge of its pathogenesis, and lesser known clinical features such as pneumonitis, encephalitis and glomerulonephritis. PMID- 8502776 TI - Chlamydia-induced reactive arthritis. AB - Chlamydia trachomatis infection is now recognized as the most prevalent veneral disease in the Western World. The majority of cases of Reiter's syndrome, one type of reactive arthritis, are secondary to sexually transmitted infections. Evidence of urogenital C. trachomatis infection is found in 36% to 61% of cases of Reiter's syndrome. We investigated the prevalence of infection by this organism in a group of patients with spondyloarthropathies. Positive cultures were obtained in 39.4% of patients with Reiter's syndrome, as well as in 22.2% of patients with psoriatic arthritis and in 20% of patients with ankylosing spondylitis. An important percentage of patients also had positive serum antibodies against C. trachomatis (62.1% of patients with Reiter's syndrome), suggesting presence of infection at some point during the course of the disease. Our findings and those from other authors support the use of long-term antibiotic therapy in patients with reactive arthritis, mainly in those in whom positive culture for C. trachomatis has been obtained as well as in their sex partners. PMID- 8502777 TI - Gonococcal arthritis. AB - Disseminated gonococcal infection is a preventable communicable disease. It is an important cause of arthritis in sexually active adults. Prompt recognition and treatment of this common disease results in cure and eliminates unnecessary diagnostic procedures and prolonged hospitalization. PMID- 8502778 TI - Syphilitic arthritis and osteitis. AB - Syphilis again has become a significant clinical problem and clinicians must reacquaint themselves with the classic as well as the changing clinical manifestations, new diagnostic methods, interaction with HIV infections, and outcomes of therapy. Musculoskeletal manifestations can be associated with congenital, secondary, and tertiary syphilis and can mimic a wide variety of rheumatic and systemic diseases of worse prognosis. Musculoskeletal manifestations due to congenital and secondary syphilis usually subside completely after accurate diagnosis and antibiotic therapy. PMID- 8502779 TI - Lyme disease. AB - The clinical features of Lyme disease have been well documented since its description as a distinct clinical entity in 1975. A better understanding of the diversity of Borrelia strains and species that cause the disease as well as new insights into the immunology and pathogenesis of Lyme disease help explain some of the observed variations in clinical manifestations. The diagnosis of Lyme disease may be straightforward when patients in endemic areas present with typical clinical features; however, the diagnosis should be in doubt when the clinical picture is nonspecific or atypical, or a feasible exposure history cannot be obtained. Laboratory diagnosis is primarily based on serologic techniques, but interpretation of test results can be fraught with uncertainty. Treatment with appropriate antibiotics is successful in the majority of cases of Lyme disease. However, some patients may not respond, and in these cases multiple repeated courses are usually ineffective and unwarranted. More data are needed to determine the appropriate treatment of Lyme disease during pregnancy, and the appropriate management of ixodes tick bites. A suitable arthropod vector and a competent animal reservoir host are essential for perpetuating Lyme disease in a geographic location. The intricate ecologic forces at work are well understood in certain endemic areas but are poorly defined elsewhere, particularly where the disease is sporadic or its existence is in question. Prevention of Lyme disease is best achieved through education regarding avoidance of the tick vector. A vaccine using a recombinant form of the OspA protein of B. burgdorferi has been successful in animal models. Whether an effective human vaccine can be developed remains unknown. PMID- 8502780 TI - Candida arthritis. AB - Septic arthritis can be caused by Candida species. Its true incidence is unknown because only a few cases have been reported. Two clinical syndromes have been identified. The first is an isolated monarthritis caused by the direct intra articular inoculation of fungi that inhabit the skin, by means of an injection, or during surgery. The second is the development of a mono- or polyarthritis as a complication of hematogenously disseminated candidiasis. The optimum treatment of this condition is not yet known, although the combination of medical and surgical treatment seems to be the most convenient therapeutic modality. Amphotericin-B continues to be the drug of choice. PMID- 8502781 TI - Other fungal arthritides. AB - Fungi are not a common cause of musculoskeletal infection; however, reports of fungal bone and joint infections have lately surged and are expected to increase more. There is evidence of an increasing incidence of pathogenic and opportunistic fungal infections and emergence of new species of disease-causing fungi, particularly in immunosuppressed patients. Distribution is worldwide, signs of infection can be mild, and chronic evolution as well as delayed diagnosis are common. PMID- 8502782 TI - Parvovirus B19 infection. AB - Human parvovirus B19 is a recently discovered and characterized DNA virus. B19 infection in the community is common and widespread. A number of well-known clinical syndromes have now been ascribed to B19 infection. Of rheumatologic interest, B19 infection causes adult erythema infectiosum which may be associated with a rheumatoid-like syndrome of symmetric polyarthralgia and polyarthritis. Presenting symptoms and signs may be limited to the joints. Some adults develop a chronic arthropathy that needs to be differentiated from early classic rheumatoid arthritis. Evidence for persistent B19 infection suggests that human parvovirus B19 infection may serve as a model for the study of virus-host interactions and the role of viruses in the pathogenesis of rheumatic diseases. PMID- 8502783 TI - Human immunodeficiency virus (HIV) infection and arthritis. AB - A variety of inflammatory arthritic conditions are observed in the setting of HIV infection. The epidemiology of these disorders is a point of current controversy, although it appears that several unique syndromes are clinically associated. The pathogenesis of these disorders remains unclear, but we hope that further work in this area will lend important insights into the mechanisms of both HIV-associated and non-HIV associated rheumatic disease. The overall management of such patients is based on recognizing the underlying HIV infection and the judicious use of antirheumatic drug therapy. Rheumatologists need to be aware of the natural history of HIV infection and its clinical manifestations. PMID- 8502784 TI - Rheumatic manifestation of human leukemia virus infection. AB - Rheumatic disorders associated with retroviruses are described in this article. A recent study of human T-cell leukemia virus type-I (HTLV-I) revealed that it appeared to be associated with the pathogenesis of several immune disorders such as myelopathy, broncho-pneumopathy, Sjogren's syndrome, and arthropathy. HTLV-I associated arthropathy (HAAP) shows remarkable synovial proliferation with nuclear convoluted T-cell infiltration in both synovium and synovial fluid. Synovial cells obtained from HAAP patient-integrated HTLV-I proviral DNA and also expressed mRNA for HTLV-1 tax gene; moreover, HTLV-1 integrated synovial cell clones expressed a high level of mRNA for several oncogene and growth factors compared with HTLV-I non-integrated clones. These findings suggest that HTLV-I is the first exogenous retrovirus that contributes to synovial proliferation with immune disorders in humans. PMID- 8502785 TI - Musculoskeletal syndromes in parasitic diseases. AB - Parasitic infestation can induce a variety of rheumatic syndromes as a result of infiltration of musculoskeletal structures by parasites or an immune mediated mechanism. Parasite-induced symptoms should be considered when arthritis, enthesitis, myositis, or vasculitis develop in patients residing in endemic areas and in certain subsets of the population of developed countries, for example, migrants, travelers, and immunocompromised individuals. Diagnosis is based on the demonstration of infection with a pathogenic parasite, lack of response to anti inflammatory agents, and improvement following antiparasitic therapy. Treatment consists of erradication of the parasite. PMID- 8502786 TI - A decade of studies of human exposure: what have we learned? AB - All four TEAM Studies operated on the basis concepts of probability sampling and direct measurement of exposure. These concepts made possible the discovery that, for nearly all of the 50 or so targeted pollutants, personal exposures exceeded outdoor levels by large margins. The conclusion, corroborated in part by other studies around the world, is that the major sources of exposure are personal activities and consumer products. This result is at odds with most existing environmental legislation, which generally does not deal with products or with indoor air in homes, in favor of regulating "major" stationary and mobile sources. These sources, however, provide only between 2-25% of personal exposure to most of the two dozen or so toxic and carcinogenic VOCs and pesticides included in the TEAM Studies. Several official publications have accepted this point, finding that funding priorities are skewed, with lower-risk problems receiving more funding than higher-risk problems such as indoor air pollution. However, just as exposures are due to small nearby sources, control of exposures can often be instituted by small individual actions. Among these are stopping smoking, reducing or eliminating the use of moth balls and bathroom deodorizers containing p-dichlorobenzene, reducing or eliminating the use of dry-cleaned clothes or airing them out for a day, and maintaining dust-free homes. PMID- 8502787 TI - Limitations to benzene cancer risk assessment by Cox and Ricci. PMID- 8502788 TI - Uncertainty in cancer risk estimates. AB - Several existing databases compiled by Gold et al. for carcinogenesis bioassays are examined to obtain estimates of the reproducibility of cancer rates across experiments, strains, and rodent species. A measure of carcinogenic potency is given by the TD50 (daily dose that causes a tumor type in 50% of the exposed animals that otherwise would not develop the tumor in a standard lifetime). The lognormal distribution can be used to model the uncertainty of the estimates of potency (TD50) and the ratio of TD50's between two species. For near-replicate bioassays, approximately 95% of the TD50's are estimated to be within a factor of 4 of the mean. Between strains, about 95% of the TD50's are estimated to be within a factor of 11 of their mean, and the pure genetic component of variability is accounted for by a factor of 6.8. Between rats and mice, about 95% of the TD50's are estimated to be within a factor of 32 of the mean, while between humans and experimental animals the factor is 110 for 20 chemicals reported by Allen et al. The common practice of basing cancer risk estimates on the most sensitive rodent species-strain-sex and using interspecies dose scaling based on body surface area appears to overestimate cancer rates for these 20 human carcinogens by about one order of magnitude on the average.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8502789 TI - The U.S. EPA Geographic Information System for mapping environmental releases of Toxic Chemical Release Inventory (TRI) chemicals. AB - This study characterizes the environmental releases of toxic chemicals of the Toxic Chemical Release Inventory (TRI) in the southeastern United States by using the U.S. Environmental Protection Agency (EPA) Geographic Information System (GIS) to map them. These maps show that the largest quantities of TRI releases in the Southeast are usually near densely populated areas. This GIS mapping approach takes the first steps in defining those areas in the region which may be potential exposure zones and which could be strategic targets for future risk screening efforts in this geographic area. PMID- 8502790 TI - Upper confidence limits on excess risk for quantitative responses. AB - The definition and observation of clear-cut adverse health effects for continuous (quantitative) responses, such as altered body weights or organ weights, are difficult propositions. Thus, methods of risk assessment commonly used for binary (quantal) toxic responses such as cancer are not directly applicable. In this paper, two methods for calculating upper confidence limits on excess risk for quantitative toxic effects are proposed, based on a particular definition of an adverse quantitative response. The methods are illustrated with data from a dose response study, and their performance is evaluated with a Monte Carlo simulation study. PMID- 8502791 TI - [Corticoids and chronic obstructive bronchopneumopathies]. PMID- 8502792 TI - [Role of anti-infective treatments in the management of chronic obstructive bronchopneumopathies]. PMID- 8502793 TI - [Ventilator weaning after the return home]. PMID- 8502794 TI - [Respiratory rehabilitation in patients with obstructive ventilatory disease]. PMID- 8502795 TI - [Treatment of chronic hypoxemia in COPD]. PMID- 8502796 TI - [Evaluation of the quality of life in persons with COPD]. PMID- 8502797 TI - [Nutritional support in chronic obstructive bronchopneumopathy]. PMID- 8502798 TI - [Symptomatic pharmacological treatment of dyspnea]. PMID- 8502799 TI - [Smoking cessation]. PMID- 8502800 TI - [Role of surgery in the treatment of chronic obstructive pneumopathies]. PMID- 8502801 TI - [Chronic obstructive bronchopneumopathies. An ethical approach]. PMID- 8502802 TI - [Treatment of chronic obstructive bronchopneumopathies]. PMID- 8502803 TI - [Physiopathological basis of COPD treatment]. PMID- 8502804 TI - [Bronchial mucus modifiers, antioxidants and antiproteases]. PMID- 8502805 TI - Kinetic concepts in the treatment of breast cancer. PMID- 8502806 TI - Salvage treatment after local breast cancer relapse. PMID- 8502807 TI - Primary chemotherapy for resectable breast cancer. PMID- 8502808 TI - Radiation therapies for breast cancer: current knowledge on advantages and disadvantages. AB - Radiation therapy continues to be the most effective adjunct to surgery to achieve long-term local control of breast cancer. In this respect it is more effective than both adjuvant cytotoxic therapy and adjuvant tamoxifen. Radiation therapy therefore plays an important role in the primary management of selected groups of breast cancer patients. However, radiation therapy may be related to potentially serious side effects, including ischemic heart disease and pneumonitis. After breast-conserving surgery radiation therapy may also compromise the cosmetic outcome. An appropriate treatment technique and avoidance of excessive treatment is essential to decrease the risk of adverse side effects. Concomitant administration of chemotherapy should probably be avoided, as well as treatment schedules with single fractions in excess of 2 Gy. PMID- 8502809 TI - How to combine adjuvant chemotherapy and radiation therapy. PMID- 8502810 TI - A new paradigm for breast cancer. PMID- 8502811 TI - What did we learn from the results of the international overview about the effects of endocrine therapy? PMID- 8502812 TI - The world overview at 10 years: what did we learn about the results of chemotherapy? PMID- 8502813 TI - From the overview to the patient: how to interpret meta-analysis data. PMID- 8502814 TI - High-dose adjuvant chemotherapy for high-risk breast cancer. PMID- 8502816 TI - Adjuvant systemic therapy: overview. PMID- 8502815 TI - Maintenance tamoxifen after induction postoperative chemotherapy in node-positive breast cancer patients: the Eastern Cooperative Oncology Group Trials. PMID- 8502817 TI - Assessment of quality of life and benefits from adjuvant therapies in breast cancer. PMID- 8502818 TI - Coping and survival in early breast cancer: an update. PMID- 8502819 TI - How to compare quality of life of breast cancer patients in clinical trials. International Breast Cancer Study Group. PMID- 8502820 TI - A laboratory model to explain the survival advantage observed in patients taking adjuvant tamoxifen therapy. PMID- 8502821 TI - Psychosocial issues in breast cancer clinical trials. PMID- 8502822 TI - Quality-of-life considerations in the adjuvant setting: critical review. PMID- 8502823 TI - Long-term sequelae from adjuvant chemotherapy. PMID- 8502824 TI - Long-term toxicity of tamoxifen. AB - Long-term tamoxifen has generally only few and usually mild adverse side effects. More serious, potentially life-threatening toxicities are rare. Aside from the ocular effects, most documented side effects appear to be related to the estrogenic properties of tamoxifen, for instance, thrombembolic disease and endometrial cancer. On the other hand, these properties may also be beneficial, for instance, they may contribute to a decreased risk of cardiac disease and osteoporosis. The potential association between tamoxifen and other possibly estrogenic side effects such as liver cancer and tamoxifen-induced tumor growth in patients with acquired tamoxifen resistance remain controversial. PMID- 8502826 TI - Financial costs, benefits, and patient risk preferences in node-negative breast cancer: insights from a decision analysis model. PMID- 8502825 TI - New endocrine agents for the treatment of breast cancer. PMID- 8502827 TI - Long-term toxicity and economic aspects: critical review. PMID- 8502828 TI - Adjuvant therapy of primary breast cancer: closing summary. PMID- 8502829 TI - Mechanisms of treatment failure. PMID- 8502830 TI - Prognosis of breast cancer patients: how to use what? PMID- 8502831 TI - DNA flow cytometry measurements and their clinical relevance in node-negative breast cancer patients. PMID- 8502832 TI - Tumor stem cells and the curability of early human breast cancer. PMID- 8502833 TI - Review of proliferative variables and their predictive value. PMID- 8502834 TI - Prognosis and prediction for early breast cancer. PMID- 8502835 TI - Trials of breast conservation: a critical review of all options. PMID- 8502836 TI - Selection and technique for lumpectomy. AB - The preoccupation with local recurrence in breast-conserving surgery represents the dominance of anatomic worries over biologic ones and is similar to the concerns that led our ancestors to devise the radical mastectomy which we now know to be an inappropriate solution to the cancer problem. Local recurrence in a conserved breast is not seen to be a cause of distant failure or death, but is often a reflection of metastases in those patients that have them. With the advent of adjuvant chemotherapy, even in node-negative cases, we have seen a conspicuous decline in local recurrence rates. The vast majority of patients with primary breast cancer can be safely and adequately treated by lumpectomy with radiation therapy and axillary dissection. Local recurrence rates are suppressed by the routine addition of adjuvant therapy. Careful attention to the principles of breast-conserving surgery will give the best cosmesis and the best rates of local control. PMID- 8502837 TI - Dealing with the devastation of stroke. PMID- 8502838 TI - Quality of life after stroke: exposing a gap in nursing literature. AB - Cerebrovascular accidents are the third leading cause of death in the United States. Stroke disables two thirds of its survivors; of these, one third are severely impaired. Studies have begun only recently to focus on the emotional and psychosocial aspects of stroke recovery. Research on quality of life has been conducted with clients suffering from cancer and osteoarthritis as well as clients recovering from cardiac surgery; apparently, however, no similar study has been conducted with stroke patients. This article highlights the gap in nursing literature regarding quality of life after a stroke and encourages nurses to conduct research on this topic. PMID- 8502839 TI - Perceived needs of wives of stroke patients. AB - The purpose of the study described in this article was to determine the difference between the importance that wives of hospitalized stroke patients attached to their own needs and the degree to which they felt those needs were met by members of the nursing staff. Fourteen wives whose husbands had survived an initial stroke completed the Stroke Family Inventory, a 27-item self administered questionnaire, and participated in a structured private interview to further explore the impact of the stroke on their lives. The wives were asked to reflect on their needs as perceived during the acute stage (the first 2 weeks) of the stroke. Of the 27 needs identified by the wives, four were perceived to be most important. These were (a) a wife's need to know what she could do to assist with her husband's care, (b) a need to be included in discharge planning for her husband, (c) a need to know that nursing personnel cared about her husband, and (d) a need to know what kind of activities her husband was able and/or would be able to do. Results showed that the wives perceived that 18 (66%) of the 27 needs were not met very well by hospital nursing staffs. PMID- 8502840 TI - Using social support theory to care for CVA patients. AB - The purpose of this article is to describe how social support theory was used to guide the nursing care of patients admitted to a rehabilitation unit in a large teaching hospital in a metropolitan medical center. Criteria from Caplan's Social Support Theory (Caplan & Killilea, 1976) were used to outline a plan that included input from significant others to create a plan for their loved ones who were recovering from left-side CVAs. All nursing care was based on the cognitive and intellectual abilities of the patients. Two case studies are presented to illustrate the use of these nursing protocols. PMID- 8502841 TI - Effect of a supportive-educative nursing intervention on older adults' perceptions of self-care after a stroke. AB - The purpose of this study was to test the effects of an individually focused, guided decision-making intervention on individuals' perception of self-care ability following a stroke. A convenience sample of 68 individuals participating in four stroke rehabilitation programs in southeast Florida participated in the study. A quasi-experimental design using a pretest and a posttest was implemented. Findings indicated the potential effectiveness of this intervention in significantly increasing individuals' perceptions of their self-care ability after a stroke. Implications for practice and future research are discussed. PMID- 8502842 TI - Comparison of the effectiveness of two bowel programs for CVA patients. AB - The purpose of the study described in this article was to compare the effectiveness of two bowel training programs for patients who had experienced a cerebrovascular accident (CVA) and to determine the length of time required to establish a regulated program. A quasi-experimental design was used to compare the existing bowel program that incorporated every-other-day digital stimulation (DS) with a program using daily DS. The convenience sample of 48 CVA patients included 23 in the control group who had DS every other day and 25 in the experimental group who had daily DS. Demographic data showed no significant differences between the two groups. The t-test showed that more subjects in the experimental group established regularity; however, the subjects in the control group who did achieve regularity took less time to do it. Subjects with right side hemiplegia and less mobility required more time to become established. As a result of these findings, the routine protocol for bowel training in this rehabilitation unit has been changed to include daily digital stimulation. PMID- 8502843 TI - The bite of a wolf: systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown etiology that occurs in people who have an aberrant immune system; it affects most major organ systems. People with SLE vacillate between periods of remission and exacerbation, with symptoms of fatigue and chronic pain, and experience disturbances in self-concept. SLE no longer has the high mortality rate of past years due to improved diagnostic tests that allow for earlier detection and treatment. SLE is a complex disease that affects the individual and the family. Rehabilitation nurses should use a holistic approach to treat altered functional ability and help individuals adjust to lifestyle changes associated with chronic illness and/or disability. Nurses with specialized rehabilitation knowledge and skill can help individuals with SLE realize and reach their optimal level of functioning, and thus improve their quality of life. PMID- 8502844 TI - A cardiac rehabilitation compliance assessment tool. AB - The Cardiac Rehabilitation Compliance Assessment (CRCA) tool was developed by the author to facilitate compliance among cardiac rehabilitation patients with their exercise and medical regimen. The 18-item tool is based on a review of the cardiac rehabilitation literature and the results of a telephone survey of cardiac rehabilitation patients who dropped out of an outpatient program (in other words, they had attended fewer than 18 of 36 sessions). The items are organized into six categories. Each item is assigned a value of 0 to 6 by the nurse. Items are totaled to determine if the patient is at high, moderate, or low risk for dropping out of the program and for noncompliance. Individualized motivational care plans can be formulated based on the CRCA assessment data. PMID- 8502845 TI - Discharge of a ventilator-dependent quadriplegic patient from a critical care unit to home. PMID- 8502846 TI - 'My wild nurse'. PMID- 8502847 TI - The accessibility of research findings. PMID- 8502848 TI - The characteristics of clients and public health nurses in child health services interactions. AB - The purpose of this paper is to describe the characteristics of clients (i.e. mothers) and public health nurses in child health services based on interviews of the mothers and the public health nurses. In addition, the meaning of the visit to the participants is described. The data were collected by interviewing 20 mothers in their homes and 20 public health nurses. Grounded theory was used in the data analysis. Four categories describing the clients were found: disengaged clients, interested but shy clients, interested but disappointed clients and eager and responsible clients. Three types of public health nurses were identified according to their own descriptions: families' needs are the more important, balancing and orders are the most identified. Client's satisfaction depended on the mother's mood, the child's behavior during the visit, having the same nurse and especially the public health nurse's character or personality. The paper emphasizes the importance of nursing research on interactions in health care, especially client-public health nurse relationships and their consequences for both parties. PMID- 8502849 TI - The psychogeriatric nurse's decision-making process in a mental hospital. AB - This article looks at the psychogeriatric nurse's decision-making process in a mental hospital. The subjects consist of 26 nurses working on the psychogeriatric wards of one hospital. The data were collected by a questionnaire (N = 26), content analysis of nursing plans (N = 56), and observation of nursing plans meetings (N = 15). The results on the different phases of the decision-making process suggested that nurses had little difficulty with the identification of problems. Data collection tended to concentrate on the physical side of nursing work. The setting of explicit targets for nursing care proved to be difficult. The vast majority of the nurses (85%) felt that decision-making on different nursing alternatives was only moderately or not at all successful. Over half of the nurses felt that their ability to evaluate the outcome of treatment and nursing was either satisfactory or poor. PMID- 8502850 TI - Cases of elder abuse, intervention and hopes for the future, as reported by home service personnel. AB - This study aimed at describing cases of elder abuse reported by witnesses, intervention offered and opinions of further intervention strategies. Home service personnel from various parts of Sweden reported 97 cases. The abused person was a women in 75% of the cases. Many of the abused persons were physically and psychologically handicapped. In most of the cases the perpetrator was a spouse or a child and in one third of the cases they had a caregiving responsibility. Psychological abuse together with financial exploitation was most frequently reported. The perpetrators' possibilities to profit financially from the abused and the family conflicts were commonly reported to be contributory causes. In 75% of the cases intervention was offered. The Swedish welfare system has no specific intervention strategies in case of abuse of the elderly and therefore more possibilities to intervene and more research concerning intervention are needed. PMID- 8502851 TI - Nurse turnover with special reference to factors relating to nursing itself. AB - Nurse turnover may decrease the quality of nursing care due to the loss of knowledge. It also results in high costs for the employer. Hence, the factors contributing to nurse turnover, if correctly understood, are important in order to know how to reduce it. This study aimed at exploring what contributing factors nurses who had decided to leave referred to concerning their decision to resign. A questionnaire was posted to all nurses who had left within one county council and 142 nurses responded. The most important factors behind the decision to leave turned out to be the following: difficult to implement changes, lack of influence and recognition, to much weekend and evening duty as well as the psychological burden inherent in nursing. The importance of the first three factors became significantly more important when those who remained in the geographical area were compared with those who moved or started to study. The findings support the idea that job satisfaction indirectly influences nurses turnover. However, it also points to the fact that what increases job satisfaction in nursing may need further research. Psychological burden for instance has not been taken into consideration before. In order to increase job satisfaction, thereby reducing nurse turnover, influence and recognition, lessening of the psychological burden and individually planned work schedules seem to be the most important factors. PMID- 8502853 TI - The attitudes towards menstruation among Icelandic nursing students--their relationship with menstrual preparation and menstrual characteristics. AB - The purpose of this study was to describe the attitudes towards menstruation of Icelandic female nursing students and see if a relationship exists between the attitudes with recollection of menarche and characteristics of present menstruation. Findings show that the students (N = 178) view menstruation as natural, not very predictable or debilitating, even though they do not deny that menstruation can effect behaviour in some way. Findings also indicate that the heavier the menstrual flow, the less likely the student is to deny all affects of menstruation as well as finding menstruation more debilitating and more predictable; the longer the menstrual period the more predictable is the coming of the next menstrual period and the less likely is the student to deny all effects of menstruation. It is suggested that inconveniences brought about by menstruation influence the formation of menstrual attitudes. PMID- 8502852 TI - Coping ability and functional status in a Swedish population sample. AB - The paper presents reference values of the questionnaires Sense of Coherence scale (SOC), measuring self-rated prerequisite for coping ability, and Sickness Impact Profile (SIP), measuring self-rated functional status. The sample used is randomly selected from a Swedish urban population consisting of 145 individuals (75 women, 70 men), divided into three age groups, 26-40, 41-55 and 56-70 years. The mean SOC score was 151 (SD 18) and was not related to gender or age. The total SIP score was low (median 0) as expected in a general population. However, again as expected, the results revealed the functional status being worse in the older group of individuals than in the younger ones. The results might give further validity to the test. The SOC scores were significantly correlated to the overall SIP scores and to the subscales of mental and social character and not to those of a physical nature. Thus, the weaker the SOC the worse the functional status. These findings are suggested to give the Sense of Coherence scale a discriminating validity. A single item concerning general health was also rated by the individuals showing the better the general health the stronger the SOC and the less the dysfunction. PMID- 8502854 TI - Social networks--the metaphor that became a research approach--a research approach in the field of nursing? AB - This article discusses whether the concept of social networks can be an effective approach for use in nursing research in Norway and Scandinavia. It also describes areas which may be especially well suited for this approach. The article does not answer the question as to whether nursing research should make use of social network studies, but it is concluded that this is one of the approaches which must be considered closely in connection with nursing research. PMID- 8502856 TI - Female urinary incontinence--psychosocial impact, self care, and consultations. AB - One hundred and eighty-seven Norwegian women with urinary incontinence (UI) were interviewed after having responded to a marketing campaign for incontinence aids. Nineteen per cent stated that UI was a negligible problem. Urge incontinence was associated with more mental distress, practical inconveniences, and social restrictions than stress incontinence. Young women were more handicapped by stress incontinence than old women. Severe incontinence was associated with more mental distress and practical inconveniences than slight incontinence. A wide variety of control measures was used, the most popular being absorbent products. Only four had not used any control measure. Fifty-seven per cent had mentioned their UI-problem with a doctor. The consultation rate increased with the severity and duration of UI. Only 36% were satisfied with the outcome of the consultation. PMID- 8502855 TI - A survey of Swedish mothers' view on breastfeeding and experiences of social and professional support. AB - The purpose of this cross-sectional study was to investigate conditions for breastfeeding among 452 mothers. Three different groups of women, participating in the Swedish health care system, were asked to complete a questionnaire about breastfeeding and related issues: 1) pregnant women attending the pregnancy care centres (n = 186), 2) women staying at the maternity wards after delivery (n = 171) and 3) women with two-month-old child attending the child health stations (n = 95). We found that the majority of the mothers were in favour of breastfeeding and intended to or had begun to breastfeed their infants. The main problems were "sore nipples", "children who cannot take the breast" and "insufficient milk production". Negative experiences of previous breastfeeding and overwhelming demands were motives for weaning. The personnel within the health care system were shown to be important for the mothers as regards advice and support. However, we found that certain routines could be revised to strengthen the mothers' attitude towards breastfeeding: 1) information on and discussions about breastfeeding occurred infrequently at the pregnancy care centres. 2) Water or formulated milk was often given to the newborn baby at the maternity wards and 3) the participation of the fathers was limited. Continuous surveillance of the routines and education of the health care staff would be desirable to enable them to give the mothers the right breastfeeding support and advice at the right time. PMID- 8502857 TI - A new injection technique for insulin treatment, simpler to use and as effective? PMID- 8502858 TI - [Congenital deficiencies in bile acid synthesis: from diagnosis to treatment]. AB - Bile acids represent the principal excretion pathway of cholesterol. Their synthesis involves hydroxylations of the sterol nucleus and shortening of the lateral chain transforming an highly insoluble and immiscible molecule in an hydrophilic and detergent one. Congenital defect of one of the enzymes of bile acid synthesis (26-alpha-hydroxylase) constitutes the etiology of cerebrotendinous xanthomatosis, associating degenerative disease of the central nervous system, cutaneous xanthomas and cataract; the degenerative process may be stopped by a substitutive therapy with chenodeoxycholic acid. In another syndrome characterised by a lack of peroxisomes (Zellweger disease and associated syndromes), some bile acid metabolites accumulate due to the enzymatic block. Some cases of malabsorption due to a congenital defect of bile sterol synthesis are reported; such a case was jointly investigated in Brussels and Groningen. PMID- 8502859 TI - [Biological aspects of treatment of hyperthyroidism]. AB - A woman treated for hyperthyroidism is described. This case illustrates two aspects of the laboratory follow-up of hyperthyroidism: sequential measurements of sensitive TSH and of the parameters of calcium metabolism. PMID- 8502860 TI - [Prevention of bacterial endocarditis: current recommendations]. AB - International consensus has been reached on the guidelines of prevention programmes of bacterial endocarditis in patients bearing a valvulopathy and submitted to various diagnostic or surgical procedures. They are presently characterised by: 1) targeting of indications: less procedures have to be covered by an appropriate antibiotic and owing to progresses made in ultrasonography, less patients with mitral valve prolapse have to be protected; 2) simplification of the administration of the antibiotics: priority is given to the oral route and two doses are sufficient, one before, and one after the procedure; 3) the dropping of penicillin V and the questioning of erythromycin: amoxicillin becomes the first-choice drug, more often administered orally than parenterally; in case of allergy to beta-lactams, clindamycin takes precedence over macrolides. Those new strategies for antibiotic prophylaxis should reveal themselves better followed, more performant and less expensive. PMID- 8502861 TI - [Anemia in an elderly man]. PMID- 8502862 TI - [Chronic obstructive bronchopneumopathy]. PMID- 8502863 TI - [Surgical techniques]. PMID- 8502865 TI - [Cholecystectomy by way of celioscopy. Proceedings of a new technique]. PMID- 8502864 TI - [Digestive celiosurgery. Nurses experiences]. PMID- 8502866 TI - [Surgical celioscopy. Disinfection and sterilization of equipment]. PMID- 8502867 TI - [Anatomic and physiologic reminder]. PMID- 8502868 TI - [The patient in pain]. PMID- 8502869 TI - [Inguinal hernias. Definition and treatment]. PMID- 8502870 TI - [Pathology of the pancreas]. PMID- 8502871 TI - [Myringoplasties]. PMID- 8502872 TI - [Plastic surgery of the ossicles]. PMID- 8502873 TI - [Otosclerosis]. PMID- 8502874 TI - [Chronic cholesteatomatous otitis]. PMID- 8502875 TI - [Hearing and ear pathologies. The nurse's role]. PMID- 8502876 TI - [Repair surgery of the middle ear: nursing care]. PMID- 8502878 TI - [The middle ear. Anatomical and physiological recall]. PMID- 8502877 TI - [The totally laryngectomized patient and the nursing staff]. PMID- 8502879 TI - [Tracheotomy 1]. PMID- 8502880 TI - [Serous otitis]. PMID- 8502881 TI - [Genetics. Observations in the guise of an editorial]. PMID- 8502882 TI - [The Vaud register of congenital abnormalities]. PMID- 8502883 TI - [Chromosome abnormalities in solid tumors: various examples studied at the department of medical genetics]. PMID- 8502884 TI - [Cytogenetics of malignant hemopathies]. PMID- 8502885 TI - [Fluorescent in-situ hybridization and molecular cytogenetics]. PMID- 8502886 TI - [Molecular analysis of 68 Swiss-Romance subjects at risk for fragile X syndrome]. PMID- 8502887 TI - [Cytogenetic studies of fetal blood: biological disturbances associated with karyotype abnormalities]. PMID- 8502888 TI - [Contribution of developmental pathology to medical genetics]. PMID- 8502889 TI - [What can be expected of the Human Genome Project?]. PMID- 8502890 TI - [Parallel or complementary medicine?]. PMID- 8502891 TI - [Parallel medicines. Report by the Council of State to the High Council on Claude Ogay and associates' asking the study of the creation of a Chair concerning the treatment by natural and complementary medicines and techniques (non-conventional medicines) at the University of Lausanne]. PMID- 8502892 TI - [Transvaginal ultrasonography in the diagnosis of abnormal uterine bleeding in women of reproductive age. Comparison with transvesical ultrasonography]. AB - We undertook this study to compare the diagnostic value of endovaginal sonography and transvesical sonography in the diagnosis of abnormal uterine bleeding in reproductive age women in Yaounde (Cameroon). 130 consecutive patients were included in this prospective study. Inclusion criteria were the presence of a missed period and abnormal uterine bleeding, absence of local or vaginal lesion on speculum examination, and the performance of transvaginal and transabdominal sonography within 12 hours. The results of each technique were compared for image quality and diagnostic information. The diagnoses included ovarian cyst (33), abnormal intra-uterine pregnancy (22), ectopic gestation (14), endometrial abnormality (14), fibroids (11), normal intra-uterine pregnancy (4), appendicitis (1), no abnormality (12). Transvaginal sonogram was of better image quality in 108 patients (83.1%). It provided more diagnostic information in 99 patients (76.1%). For 38 patients (29.2%), it provided pertinent information which altered the diagnosis made after transvesical sonography. Our results suggest that endovaginal sonography should be considered the first sonographic technique to use for reproductive age patients with abnormal uterine bleeding in Yaounde (Cameroon). PMID- 8502893 TI - [Using prenatal care in the Tunisian context: barriers and motivation factors]. AB - Several barriers to and motivators of antenatal care are analysed in the context of a developing country. The authors found that socio-cultural factors are as important as organizational factors in motivating women to seek antenatal care. While social and economic development may improve the quality of life in the long term, it is important to respond now to the needs of pregnant women in order to encourage them to use such services. A comprehensive analysis of certain organizational factors would be useful in achieving this goal. PMID- 8502894 TI - [HELLP syndrome. Epidemiological, nosological and prognostic aspects]. AB - The authors report a prospective and controlled study of hellp syndrome in two groups of patients: normal and preeclamptic. Hellp syndrome was seen only in the pre-eclamptic group (19.3 per cent). Maternal prognosis was poor when Hellp syndrome was confirmed. Several maternal complications were seen: severe hypertension, subarachnoid hemorrhage, coagulation disorders and renal failure. Maternal mortality was high (16.7 per cent). Hellp syndrome does not worsen fetal prognosis, which is already compromised by pre-eclampsia. PMID- 8502895 TI - [Induced labor: conditions for success and causes of failure. A prospective study of 162 cases]. AB - The authors report the results of a prospective study of 162 cases of induced labour collected between 30 October 1990 and 31 December 1991 in the maternity unit of the Yaounde teaching hospital group. There were 1,640 deliveries during this period. Premature rupture of the membranes in 72 cases (44.4 per cent) and postmaturity in 42 cases (27.2 per cent) were the chief indications for the induction of labour in this study. There were 138 cases (85.2 per cent) of spontaneous delivery, 20 cases (12.3 per cent) of cesarean section and 4 cases (2.5 per cent) of vacuum extraction. Failure of induction occurred in 16 cases (9.8 per cent). Repeat induction of labour after a rest period led to spontaneous delivery in 6 cases. There were 6 fetal deaths, i.e. a perinatal mortality of 3.7 per cent. Postmaturity (3 cases) and premature rupture of the membranes (2 cases) were the risk factors in these six fetal deaths. Analysis of cases of failed induction and of fetal deaths in this study leads the authors to conclude that ripening of the cervix is an essential parameter for success of the artificial induction of labour. Premature rupture of the membranes, and postmaturity associated with an unripe cervix are unfavourable risk factors for the induction of labour and are potential indications for preventive cesarean section in order to avoid fetal death. PMID- 8502896 TI - [Fetal prognosis in breech delivery. Statistical study of 543 cases]. AB - The authors report a retrospective study of 543 breech deliveries during a 4-year period (1987-90). The cesarean section rate was 18.4 per cent, and perinatal mortality 3.68 per cent. Poor prognostic factors were: multiparity, large fetus, cord prolapse, second stage of labour lasting more than 30 mins and obstetric manoeuvres. Prenatal care and obstetric evaluation before labour may improve fetal prognosis. PMID- 8502897 TI - [Hysteroscopy and hysterosalpingography. Which examination to chose?]. AB - The authors report 58 patients undergoing hysterosalpingography (HSG) then hysteroscopy (HC) for investigation of the uterine cavity. Comparison of HSG and HC findings revealed the following: In 26.9 per cent of cases HC disproved or rectified the result of HSG. Results of the two investigations were in agreement in 74.1 per cent of cases. In the light of our results, and after a review of the literature, HSG is indicated as the first line investigation for exploration of the uterine cavity and/or the tuboperitoneal level. HC alone is sufficient for exploration of the cervical canal and of the uterine cavity. PMID- 8502898 TI - [Cancer of the ovary and pregnancy]. AB - Three cases of an association of carcinoma of the ovary and pregnancy are reported. The authors stress the following points: the diagnosis should be made earlier by clinical and sonographic monitoring of pregnancy; high incidence of low-malignancy forms; fetal prognosis is particularly threatened during the first three months of pregnancy; treatment can be conservative in forms limited to one ovary. PMID- 8502899 TI - [Abdominal pregnancy, a rare anatomoclinical entity. 4 case reports (1981-1990)]. AB - The opportunity is taken, on the basis of 4 cases of abdominal pregnancy and a review of the literature, to attempt to analyse the various aspects of this increasingly rare pathology. Its incidence is low, being evaluated by our own study at 4/85 757 deliveries, i.e.: 1/21 439 deliveries collected at the Maternity and Neonatology centre of Rabta Tunis during a 10-year period (1981 1990). The essential epidemiological factor is the low socio-economic and cultural status seen in the patients studied. Clinical signs were predominated by metrorrhagia, abdominal pain, disturbed intestinal function and fetal death in utero. The delay in diagnosis explains the onset of frequent fetal complications in the form of fetal death in utero (3 cases out of 4) and of various fetal malformations. Ultrasonography is the essential investigation enabling diagnosis in the presence of clinical suspicion. Surgery is obligatory, excluding any attempt in the majority of cases at extraction of the placenta, which is left in place. PMID- 8502900 TI - [Acardiac malformation: ultrasonographic diagnosis. A case report]. AB - Acardia is an extremely rare malformation which is seen in less than 1 per cent of monozygous twin pregnancies. Pathological aspects and etiopathogenic theories concerning this malformation are reviewed on the basis of a case diagnosed in utero at 24 weeks. The value of the antenatal diagnosis of this malformation is that of monitoring the progression of the pregnancy and predicting the fate of the healthy twin. PMID- 8502901 TI - [Peripartum cardiomyopathy. Analysis of 3 cases and review of the literature]. AB - Peripartum cardiomyopathy is defined as a syndrome of cardiac failure occurring in the latter part of pregnancy or in the puerperium without obvious cause and without prior evidence of heart disease. Analysis of the particular features of this syndrome and a review of the literature indicate its similarity with other cardiomyopathies in terms of clinical features, natural history and treatment, but maternal and fetal prognosis is poor. PMID- 8502902 TI - [Uterine fixation to the promontory and the Orr-Loygue operation in associated genital and rectal prolapse]. AB - The association of genital prolapse and rectal prolapse is rare. The authors report six cases of simultaneous mixed prolapse treated surgically via an abdominal approach. The latter technique enables the treatment of genital prolapse by uterine fixation to the promontory and rectal prolapse by rectopexy using the Orr-Loygue technique. Chronic constipation and obstetric trauma are constantly found among etiological factors. Four of our patients had urinary stress incontinence. There were no preoperative complications. One patient reported worsening of her constipation. Mean follow-up is only 20 months (2 months to 3 years), but no recurrences have occurred. Review of the literature and of series with more than fifteen years follow-up shows that the Orr-Loygue operation is reliable with a low complication rate and only rare recurrences. PMID- 8502903 TI - [Ten years of experience with Nova T in office practice. 630 cases]. AB - The author reports a retrospective study of 630 Nova T inserted by a medical gynecologist. The Nova T was chosen as intrauterine device because of its longevity and its ease of insertion and removal. Nulliparity was not an absolute contraindication (10% of cases in the series). Particular attention was paid to information given to the women concerned: possibility of menstrual irregularities, infections more likely to be transmitted by a partner than by the IUD, and above all the possibility of pregnancy: Pearl index 0.96. Uterine retroversion in no way interfered with the insertion technique. Hysterometry was routine (mean: 7.25 cm). Threads were cut 2-3 cm from the cervix. PMID- 8502904 TI - [The health care product: service or health?]. PMID- 8502905 TI - [Childhood cholesterolemia. A study]. PMID- 8502906 TI - [Infections isolation in the hospital]. PMID- 8502907 TI - ["... The lack of a true ideological debate at the heart of nursing is determining the future of our specialties". Interview by P. Darriba Rodriguez]. PMID- 8502908 TI - [Aspects of nursing: diverse opinions]. PMID- 8502909 TI - [Experiences with water-soluble bags in a commercial laundry for hospital use]. PMID- 8502910 TI - [Getting a diploma: closer than ever. The ROL Institute for the Development of Nursing launches a novel program of education by correspondence]. PMID- 8502911 TI - [Treadmill exercise. Blood sampling with a nursing protocol]. PMID- 8502912 TI - [Nursing, reality in crisis]. PMID- 8502913 TI - [Chronic psychiatric disease. How to decrease it]. PMID- 8502914 TI - [The nutritional status of the Kung population (the Kalahari Desert)]. PMID- 8502915 TI - [Continuing education. 77. Medical-surgical. Water balance and acid-base equilibrium]. PMID- 8502916 TI - [Don't know, don't want to or can't?]. PMID- 8502917 TI - [Job satisfaction in primary care. A survey]. PMID- 8502918 TI - [Mechanical ventilation at home]. PMID- 8502919 TI - [Family planning. The evaluation of a program]. PMID- 8502921 TI - [We ought to discover that which has meaning for people]. PMID- 8502920 TI - [Work motivation. The creation of quality circles]. PMID- 8502922 TI - [Nursing education in public health. An interesting effort carried through at the Escuela Nacional de Sanidad]. PMID- 8502923 TI - [Allergic asthma. Child training]. PMID- 8502924 TI - [The hospitalized patient]. PMID- 8502925 TI - [Trends that influence the future of nursing]. PMID- 8502926 TI - [A monitor for controlling the weight of bed-rest patients]. PMID- 8502928 TI - [On health reform in Europe]. PMID- 8502927 TI - [Continuing education. 78, Medical-surgical. Atelectasis]. PMID- 8502929 TI - [Prevention of mineral deficiencies (iron, calcium and magnesium)]. AB - The calcium, magnesium and iron intakes provided by food must be sufficient to fulfil the physiological demands of each individual, to avoid the clinical manifestations of mineral deficiencies and to ensure an optimal state of health. For these reasons, it is desirable to ensure a sufficient calcium intake (notably by milk products) at all ages and particularly in children, adolescents and young adults up to the age of 25 (and also in elderly people to prevent osteoporosis); to recommend the consumption of magnesium-rich foods, such a little sifted cereals and dry vegetables to ensure sufficient intakes; to prescribe pharmaceutical preparations on iron systematically in pregnant women and by repeated courses in infants aged 10 to 36 months (to avoid complications due to iron deficiency and notably its harmful influence on haematopoiesis). The consumption of "second age" milks for older children must also be encouraged. Finally, the consumption of foodstuffs with a high vitamin C content should be recommended as it increases the bioavailability of nutritional iron, and the consumption of substances, such as tea and coffee, which inhibit iron absorption must be reduced. PMID- 8502930 TI - [Current aspects about the role of zinc in nutrition]. AB - The role played by zinc in biology is now better known, and numerous biochemical mechanisms, such as immunity or actions on several hormones and more than 200 enzymes, have proved to be zinc-dependent. Thus, many functions are disturbed when this trace metal is deficient, including, for example, taste and appetite, cell multiplication, growth, pregnancy, fertility, defence against bacteria and brain functions. Zinc intake has been found to be unexcessive and indeed, at the limit of sufficiency in the French population. Groups at risk, such as neonates, growing children, pregnant women and elderly people, should have a higher zinc intake provided by dietary measures or supplementation. Zinc supplementation has been shown to exert a beneficial effect in randomized studies concerning children's growth, acne, old people's immunity or low female fertility. Such supplementation must be balanced and given in moderate doses since zinc interacts with other foodstuffs, and an excess of zinc can be as bad as its deficiency in our nutrition. PMID- 8502931 TI - [Vitamins and cancers]. AB - To a great extent carcinogenesis depends on the environment. Some vitamins contribute to the "exogenous" protection against aggressors (i.e., on a molecular scale, active forms of oxygen and free radicals). Epidemiology provides numerous data in favour of this protection, but these date are sometimes ambiguous or contradictory. Current, active experimental studies will probably lead to firm conclusions within the next few years. As regards vitamin A, considerable advances have been made in fundamental research (we now know its molecular mechanism of action, notably on genes) and in applied research (differentiation of leukaemic cells). In various aspects vitamin D resembles vitamin A and also acts on the haematopoietic tissue. Vitamin E is difficult to study, but its protective effect on cell membranes and structures cannot be questioned. Vitamin C emerges from a period of controversy and is increasingly studied at present: it might be a useful adjuvant for the treatment of cancers. PMID- 8502932 TI - [Nutrition and colorectal cancer]. AB - Results from case-control studies and prospective studies suggest that diet is involved in the causation of large bowel cancer either as initiator, promoter, or inhibitor of carcinogenesis. There is fairly consistent evidence concerning the protective effect of green vegetables. There is some evidence relating fat intake or protein intake to colorectal cancer whereas fiber intake or calcium intake would be inversely related to colorectal cancer. Recent data suggest that tobacco could be involved in adenoma formation and alcohol in adenoma growth. Available data are not sufficient to serve as a basis for firm specific dietary advice. In the present situation it is attractive to investigate available hypotheses within the framework of intervention trials. PMID- 8502933 TI - [Dietary prevention of dental caries]. AB - In industrialized countries, for the past few years, the decreasing prevalence of dental caries is due to the improvements of oral hygiene, alimentary prevention and water and salt fluoridation. The dental caries are promoted by the consumption of sucrose when it is too high and/or too frequent between meals. The well cooked sucrose-containing starch - are more cariogenic than sucrose alone. Prevention aims first at high consumers of cariogenic foods and at subjects who are genetically predisposed to dental caries. PMID- 8502934 TI - [Marine oils and prevention of cardiovascular diseases]. AB - Observations done in Greenland Eskimos, and then confirmed in other populations, have led to the hypothesis that a diet rich in marine oils is associated with a low incidence of coronary heart disease. Marine oils are rich in n-3 polyunsaturated fatty acids which, if consumed in large amounts, influence plasma lipid concentrations (mainly by lowering triglycerides), and modify the synthesis of eicosanoids (leukotrienes and prostanoids) with effects on haemostasis, vasomotility and inflammation. Many experimental studies suggest that fish oils may exert and anti-atherosclerotic action. However, direct evidence (through prospective preventive trials) remains insufficient to establish that dietary supplements of marine oils prevent arterial diseases in humans efficiently. Aside from the treatment of hypertriglyceridaemia, no definitive recommendation can be made about the health benefits of marine oil supplement. PMID- 8502935 TI - [Towards preventive dietetics in children]. AB - Our views on paediatric nutrition have considerably changed during the last 20 years. Some hereditary metabolic diseases testify to the remarkable efficacy of a specific preventive dietetics avoiding the development of mental retardation. Although certain deficiencies (in iron, fluorine, folates, vitamin D) are persisting in France, the major problems concern the prevention in childhood of allergy, obesity, atherosclerosis, high blood pressure, osteoporosis and even certain cancers, all diseases which play a crucial role in the morbidity and mortality of adults. Numerous uncertainties still exist, but in the present state of our knowledge we can already develop some recommendations which should replace the much abusive publicity that prevails in the information given to the public. PMID- 8502936 TI - [Dietetic prevention in elderly in France]. AB - Beside effects of dietetic recommendations on cellular or tissular ageing, dietetic prevention in elderly aims, at avoiding nutritional deficiencies in healthy old individuals and thus, the occurrence of induced diseases. Requirements of healthy housebound elderly are not different from those of adults but, more than in adults, diet's quality and palatability are important to insure maintenance of intakes. Beyond these advises, dietetic prevention in geriatrics requires screening of physical, psychical and social handicaps frequently observed in very old persons. Their additional effects could deeply modify dietary balance, especially during an acute intercurrent disease or following modifications of the environment. The practitioner's part is essential in preventing malnutrition in an old person impaired by chronic diseases: preventing the outcome of a denutrition to an irreversible state may avoid a medical and social decompensation leading to institutionalisation. PMID- 8502937 TI - [Is the treatment of arterial hypertension a nephroprotector? Effects may be different based on the class of anti-hypertensive agents used]. PMID- 8502938 TI - [Rapid magnetic resonance imaging. Applications in pediatrics]. PMID- 8502939 TI - [Oral cephalosporins. News and role in therapeutics]. PMID- 8502940 TI - [Recent data on the treatment of carotid stenosis]. PMID- 8502941 TI - [Pulmonary antiprotease defense]. AB - The pulmonary alveolar spaces are spatially organized in order to facilitate gaz exchanges. Proteases, responsible for the destruction of the connective tissue and for the disorganization of the alveolar structures, are present within the lung. Neutrophil elastase is the most important. Numerous antiproteases are present in the lung the most important being alpha-1-antitrypsin. Its blood level is diminished during an autosomal hereditary disease: alpha-1-antitrypsin deficiency. It can be corrected by infusion of purified alpha-1-anti-trypsin. PMID- 8502942 TI - [Pediculus capitis pediculosis. Did a new type of louse appear?]. PMID- 8502943 TI - [The beginnings of intensive care in France]. PMID- 8502944 TI - [Old traumas of the ankle. Diagnostic orientation]. PMID- 8502945 TI - [Fractures of the upper end of the femur in adults. Etiology, mechanism, diagnosis, development, prognosis, treatment]. PMID- 8502946 TI - [Psoriasis. Diagnosis, clinical course, prognosis, treatment]. PMID- 8502947 TI - [Chronic gastric ulcer. Epidemiology, diagnosis, clinical course, treatment]. PMID- 8502948 TI - [Peripheral facial paralysis. Diagnostic orientation]. PMID- 8502949 TI - [Increased erythrocyte sedimentation. Diagnostic orientation]. PMID- 8502950 TI - [Corticosteroids. Principles and rules of their use, posology]. PMID- 8502951 TI - [Uterine fibroma. Diagnosis, development, treatment]. PMID- 8502952 TI - [Acute peritonitis. Physiopathology, etiology, diagnosis, development, treatment]. PMID- 8502953 TI - [Epidemiology of monoclonal gammopathies]. AB - The multiple myeloma incidence rates vary from 1.5 to 4.5/100,000/year, depending on the country. Among American black people it is more than twice than among Whites. The median age is 69, with a sex ratio of 1.1. Waldenstrom's macroglobulinemia is 3-4 less frequent, whereas monoclonal gammapathy of unknown significance (MGUS) is much more common. Epidemiological studies in progress try to demonstrate genetic or environmental factors, in order to find means of primary prevention. PMID- 8502954 TI - [Cytokines and lymphoplasmocytic proliferations: essential role of interleukin 6]. AB - Interleukin 6 (IL-6) is a major in vitro growth factor for tumoral cells in human multiple myeloma and myeloma cell lines, whose growth is completely dependent on exogenous IL-6, can be reproducibly obtained. IL-6 is overproduced in patients with active myeloma, mainly by the tumoral environment. Injection of anti-IL-6 antibodies to myeloma patients with terminal disease and extramedullary proliferation completely blocked myeloma-cell proliferation in vivo and completely inhibited the C-reactive protein production. Moreover, the serum CRP level is a strong prognostic factor in myeloma, increased serum CRP levels (reflecting an increased IL-6 production) being associated with a poor prognosis. Other cytokines control the IL-6 mediated myeloma cell proliferation. GM-CSF, IL 3 and G-CSF stimulate the IL-6 responsiveness of myeloma cells without affecting the endogenous IL-6 production. Interferon-gamma completely inhibits the IL-6 mediated myeloma-cell proliferation without affecting the endogenous IL-6 production and IFN alpha and TNF alpha stimulate the proliferation of our IL-6 dependent myeloma-cell lines by inducing an autocrine production of IL-6 in these cell lines. PMID- 8502955 TI - [Antibody activities of monoclonal immunoglobulins]. AB - Monoclonal immunoglobulins present a normal structure and have an antibody activity. This activity may be directed against exo-antigens especially bacterial, but more frequently against auto-antigens. It may then be symptomatic and therefore explain unusual clinical or biological manifestations in the course of monoclonal dysglobulinemias. The most common auto-antibody activities are directed against red blood cells (responsible for cold agglutinin disease), IgG (leading to the formation of cryoglobulinemia), and myelin (responsible for peripheral neuropathy). Often, the monoclonal auto-antibody activity is asymptomatic and polyspecific, as it is only the monoclonal expression of polyclonal natural auto-antibodies. Genetic study of variable segments of heavy and light chains used by these monoclonal antibodies are useful to precise the role played by antigen in the driving of the lymphoid proliferation. These physiopathologic models concerning monoclonal gammapathies are a useful tool to understand the physiopathology of polyclonal auto-immune disease and the role of auto-antibodies. PMID- 8502956 TI - [Biological diagnosis of monoclonal immunoglobulins]. AB - The demonstration and characterization of monoclonal immunoglobulins in biological fluids are usually performed using electrophoresis coupled to antigen antibody reactions. This paper briefly discusses the most commonly used techniques. Small, often multiple serum monoclonal immunoglobulins, mostly unrelated to malignant proliferations, are frequent when using recent high resolution methods. Their pathological significance should take into account a number of physiological, clinical and biological data. PMID- 8502957 TI - [Benign monoclonal gammopathies]. AB - The finding in serum and/or urine of IgG, IgA or a monoclonal light chain must prompt a systematic search for a myeloma, a solitary plasmocytoma or an immunoglobulins amyloidosis. Clinical and experimental data suggest that some monoclonal immunoglobulins can remain stable after several years of existence, but at the time of diagnosis there is no criterium to assert with certainty that a monoclonal immunoglobulin will or will not be complicated by a malignant proliferation of plasmocytes. Nothing but a prolonged follow-up enables a diagnosis of "benign" monoclonal gammapathy to be made. PMID- 8502958 TI - [Bone and myeloma]. AB - Osteolysis induced by medullary plasmocyte proliferation is related to an increase in the number of osteoclasts in contact with myeloma cells. Osteoclast activating factors (OAF), notably lymphokines such as IL-1 beta, and IL-6, or tumour necrosis factor (TNF), produced by plasmocytes or their microenvironment, have been demonstrated. Bisphosphonates, which are potent anti-osteoclastic agents, are effective during episodes of hypercalcaemia. Their ability to delay the progression of osteolysis is being evaluated. PMID- 8502959 TI - [Significance of monoclonal macroglobulinemia]. AB - A monoclonal IgM protein in the plasma results from an expansion of a B lymphoid clone which encompasses a spectrum of different diseases: transient clones, monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia and other B lymphoid malignancies, or primary amyloidosis. The main symptoms are related to the M component concentration and specific properties, the tumor development or both. Prognosis best correlates with the underlying histologic disorder. PMID- 8502960 TI - [Cryoglobulinemia]. AB - Cryoglobulinaemia may be discovered by systematic blood examination or by the finding of a purpura reflecting a leukocytoclastic angiitis or vascular manifestations. An immunochemical study is necessary to determine whether the cryoglobulin thus found is purely monoclonal or mixed, with a monoclonal component (usually IgM) and a polyclonal IgG component, or is composed of polyclonal immunoglobulins. The principal complications of cryoglobulinaemia involve the kidneys and the nervous system. Monoclonal cryoglobulins may reveal Kahler's disease or Waldenstrom's macroglobulinaemia. Mixed cryoglobulins are often associated with autoimmune or infectious diseases, such as Epstein-Barr virus infection or hepatitis C. Treatment is difficult. In severe forms of cryoglobulinaemia plasmapheresis and chemotherapy can be used. PMID- 8502961 TI - [Tubulo-interstitial renal complications of myeloma]. AB - Tubulo-interstitial lesions are the main causes of renal failure in patients with myeloma, and they sometimes reveal this tumour. They are mainly found in large tumoral mass myelomas and are characterized by tubular lesions and specific casts of unexplained physiopathology. Symptomatic and aetiological treatments must be instituted at an early stage to obtain the recovery, at least partial, of renal function, as observed in more than 50% of the cases. The persistence of renal failure carries a sombre prognosis, which emphasizes the importance of a preventive treatment that is too often omitted. Functional tubular disorders are frequent but seldom result in Fanconi's syndrome. A better understanding of the mechanisms underlying the nephrotoxicity of monoclonal immunoglobulins should permit to reduce the incidence of tubular lesions in myelomas. PMID- 8502962 TI - [Heavy chain diseases]. AB - Heavy chain diseases (HCD) are immunoproliferative disorders characterized by the production of monoclonal immunoglobulin molecules composed of deleted heavy chains devoid of light chains. The diagnosis is established by immunoelectrophoresis (possibly combined to immunoselection) or immunofixation. The clinicopathologic features of gamma HCD are heterogenous, often somewhat similar to macroglobulinemia. Some patients show no evidence of underlying malignant lymphoproliferation. Autoimmune disorders are frequent. mu HCD is rare and often presents as chronic lymphocytic leukemia with hepatosplenomegaly and vacuolated plasma cells on bone marrow smears. Alpha chain disease is the most frequent. In its usual digestive form, the clinicopathologic pattern is uniform. The main clinical features are chronic diarrhea and severe malabsorption syndrome. At the initial stage, there is a diffuse lymphoplasmocytic infiltration of the small intestine and mesenteric nodes, sometimes reversible after treatment by antibiotics alone. At the terminal stage, a malignant lymphoma, often of immunoblastic type, occurs. The natural history and epidemiology of alpha HCD should provide insights into the pathogenesis of malignant lymphoid proliferations. PMID- 8502963 TI - [Treatment of multiple myeloma]. AB - The various chemotherapeutic regimens in multiple myeloma allow only a mean survival of less than three years. Polychemotherapy has at best a minor advantage over monochemotherapy. High dose chemotherapy followed by hematopoietic stem cell grafts yields a notable percentage of apparent complete remission. The best therapeutic choices as well as the introduction of new drugs such as alpha interferon still needs prospective evaluation. PMID- 8502964 TI - [Indications of plasma extraction during the treatment of monoclonal gammopathies]. AB - Data from the french national registry show that about 20% of plasma exchange are performed to alleviate clinical manifestations related to a monoclonal Ig. Plasma removal has to be only considered as a part of therapy, the disease being controlled by cytotoxic drugs. However, owing to its delayed effect plasma exchange are useful to preserve the functional or vital prognosis. Technical aspects such as plasma volume removed or frequency of procedures will be scheduled according to monoclonal Ig specification: repartition between intra and extravascularly pools-allotypes-efficiency of chemotherapy. Hyperviscosity syndrome, interferences with hemostasis and vascular manifestations of cryoglobulins are the main established indications. Renal insufficiency of myeloma, peripheral neuropathies and unusual clinical symptoms associated with monoclonal gammapathy of undetermined significance should also be considered as possible indications. In contrast regression of amyloidosis deposits has not been reported. PMID- 8502965 TI - [Purulent mediastinitis. A severe and frequent complication following cardiac surgery]. PMID- 8502966 TI - [Antibiotic prophylaxis in orthopedic surgery]. PMID- 8502967 TI - [Cerebral imaging and AIDS]. AB - Cerebral lesions in AIDS patients are characterized by a great variety of pathologies, except for HIV infection itself, related to the immunodeficiency context. Due to their frequent association, the interest of imagery (CT and MRI) remains essential today (despite of the underestimation of the lesions due to the weakness of the immune reactions): for the diagnosis detecting intracerebral masses (toxoplasmosis, lymphomas . . . ), white matter lesions, but also meningeal, sub ependymal or vascular lesions to obtain the diagnostic of curable pathologies as soon as possible, but also for the survey during the treatment. PMID- 8502968 TI - [The first bladder replacements in urology]. PMID- 8502969 TI - [Recent reduced visual acuity. Diagnostic orientation]. PMID- 8502970 TI - [Mitral insufficiency. Etiology, physiopathology, diagnosis, development]. PMID- 8502971 TI - [Otalgia. Diagnostic orientation]. PMID- 8502972 TI - [Acute diarrhea in infants. Diagnostic orientation and treatment]. PMID- 8502973 TI - [Constitutional cerebrovascular accidents. Epidemiology, etiology, physiopathology, diagnosis, development, prognosis, treatment]. PMID- 8502974 TI - The diagnosis of myotonic dystrophy. PMID- 8502975 TI - Seasonality of hip fracture and haemorrhagic disease of the newborn. AB - The objective is to examine and compare the seasonalities of fractured neck of femur and haemorrhagic disease of the newborn. The data are from two sources. Admissions for fractured neck of femur in Scotland over five years (1983-87) are examined by age, sex, mortality, operative intervention and source of admission. Data from the United States (1927-36) are examined for infant death rates from suspected haemorrhagic disease of the newborn 3-14 days after birth. The sine curves are examined. The rhythms, while not identical, have similarities. The peaks are in January-February and the troughs in July-August. Amongst hip fractures the peak is one month earlier and the seasonal excess around 20-25 per cent in both conditions. Rickets, haemorrhagic disease of the newborn and fractured neck of femur have comparable seasonal rhythms. Vitamin D regulates the synthesis of the vitamin K dependent bone protein osteocalcin, which is functionally abnormal in postmenopausal women. This may be a significant factor in the seasonal variation of hip fracture. PMID- 8502976 TI - Patterns of vascular pathology in acute, first-ever cerebral infarction. AB - This was a preliminary study to see whether patterns of vascular pathology correlated with a simple clinical classification of acute cerebral infarction. Thirty-two patients with acute, first-ever hemispheric cerebral infarction were prospectively studied clinically together with an extra- and transcranial Doppler ultrasound. All 14 patients with the triad of ipsilateral motor/sensory deficit, homonymous hemianopia and higher cortical dysfunction (Total Anterior Circulation Infarction, [TACI]) had occlusion of the symptomatic middle cerebral artery and/or internal carotid artery, or a severe middle cerebral artery stenosis. Three patients with lacunar infarction had no evidence of major vessel occlusion. Eleven of thirteen patients with Partial Anterior Circulation, Infarction (PACI) I (i.e. only one or two clinical features of the TACI triad) had patent symptomatic major vessels, with indirect evidence to suggest distal branch occlusion(s) of the middle cerebral artery in six. The remaining two PACI patients had major vessel occlusions. Two patients were not clinically classifiable, but both had significant vascular pathology on ultrasound. The findings of this preliminary study therefore suggest that a simple clinical classification was generally capable of predicting patterns of vascular pathology in patients with acute cerebral infarction, which could have implications for the selection of patients for clinical trials of thrombolytic therapy. PMID- 8502977 TI - A survey of exercise testing practice in Scottish hospitals. AB - A 1989 survey (unpublished) of exercise testing practice in Scotland suggested that there were important differences in the practice of exercise testing between hospitals. A postal questionnaire was sent to 30 teaching and district general hospitals in 1991 and followed up by telephone questioning of consultants. The numbers of exercise tests performed had increased to 22,012 in 1990, and a greater proportion were performed in district general hospitals. General practitioners had very limited access to the service but hospital doctors of any grade had almost free access. Rationing of early post myocardial infarction testing led to attempts to define "high risk" post infarction patients and this included inappropriate patients in many hospitals. A variety of different protocols was used. Eighteen out of 30 hospitals surveyed discontinued beta blockers but only four hospitals took account of antianginal, antihypertensive or other medication, and all but one exercised patients while on digoxin. In the majority of hospitals decisions regarding drug therapy were taken by individual physicians. A variety of personnel reported tests, many without specialist training in cardiology. Even among consultants there was no concerns on the degree of ST depression which was significant. Exercise tests performed in different hospitals in Scotland are not comparable due to the wide variation in patient selection, test conditions, and interpretation of tests. This problem is likely to be exacerbated by the multiple personnel involved in all aspects of testing. It seems probable that there is a problem throughout the United Kingdom, and that there is a need for guidelines. PMID- 8502978 TI - Benign rectal ulcer: a rare cause of life threatening haemorrhage. PMID- 8502979 TI - A case of acute respiratory failure due to tracheal compression by a thyroid cyst. AB - A patient is described who presented with sudden collapse due to acute respiratory failure caused by tracheal compression from a thyroid cyst. He made a complete recovery and the cyst was electively excised two weeks later. PMID- 8502980 TI - Should hyposplenic patients receive prophylaxis against bacterial infection? AB - The risk of overwhelming septicaemia, most commonly due to encapsulated organisms, is well recognised post-splenectomy. Although a similar risk is documented in hyposplenic patients, many physicians do not routinely give prophylaxis here. We report the case of a 41 year old woman with adult onset coeliac disease who developed pneumococcal meningitis resulting in severe residual disability and suggest that prophylaxis should be given to such individuals who have evidence of reduced splenic function. PMID- 8502981 TI - A historical review of heart failure. PMID- 8502982 TI - Pesticides and the Delaney amendment. PMID- 8502983 TI - Pesticides and the Delaney amendment. PMID- 8502984 TI - Experimental Biology '93. PMID- 8502985 TI - Immunologist to head Aging Institute. PMID- 8502986 TI - The puzzle of the triple repeats. PMID- 8502987 TI - At Rockefeller, Wiesel is the calm after the storm. PMID- 8502988 TI - Splice-site selection and decoding: are they related? PMID- 8502989 TI - The parallel beta helix of pectate lyase C: something to sneeze at. PMID- 8502990 TI - Field-flow fractionation: analysis of macromolecular, colloidal, and particulate materials. AB - Field-flow fractionation (FFF) is a family of flexible elution techniques capable of simultaneous separation and measurement. Its sample domain extends across a broad macromolecular-colloidal-particulate continuum from about 1 nanometer to more than 100 micrometers and incorporates both simple and complex macromaterials of biological, biomedical, industrial, and environmental relevance. Complex materials are separated into components to simplify measurement. Component properties measurable by FFF include mass, size, density, charge, diffusivity, and thickness of adsorbed layers. When characterization by these properties is inadequate, other measurement tools can be readily coupled to FFF, either off line or on-line, by virtue of its flow-elution operation. This article describes the principles and major subtechniques of the FFF family along with application of its measurement and separative capabilities. PMID- 8502991 TI - The three-dimensional structure of an arachidonic acid 15-lipoxygenase. AB - In mammals, the hydroperoxidation of arachidonic acid by lipoxygenases leads to the formation of leukotrienes and lipoxins, compounds that mediate inflammatory responses. Lipoxygenases are dioxygenases that contain a nonheme iron and are present in many animal cells. Soybean lipoxygenase-1 is a single-chain, 839 residue protein closely related to mammalian lipoxygenases. The structure of soybean lipoxygenase-1 solved to 2.6 angstrom resolution shows that the enzyme has two domains: a 146-residue beta barrel and a 693-residue helical bundle. The iron atom is in the center of the larger domain and is coordinated by three histidines and the COO- of the carboxyl terminus. The coordination geometry is nonregular and appears to be a distorted octahedron in which two adjacent positions are not occupied by ligands. Two cavities, in the shapes of a bent cylinder and a frustum, connect the unoccupied positions to the surface of the enzyme. The iron, with two adjacent and unoccupied positions, is poised to interact with the 1,4-diene system of the substrate and with molecular oxygen during catalysis. PMID- 8502992 TI - Secondary and tertiary structural effects on protein NMR chemical shifts: an ab initio approach. AB - Recent theoretical developments permit the prediction of 1H, 13C, 15N, and 19F nuclear magnetic resonance chemical shifts in proteins and offer new ways of analyzing secondary and tertiary structure as well as for probing protein electrostatics. For 13C, phi, psi torsion angles dominate shielding for C alpha and C beta, but the addition of hydrogen bonding and electrostatics gives even better accord with experiment. For 15NH, side chain (chi 1) torsion angles are also important, as are nearest neighbor sequence effects, whereas for 1HN, hydrogen bonding is particularly significant. For 19F, weak or long-range electrostatic fields dominate 19F shielding nonequivalencies. The ability to predict chemical shifts in proteins from known or test structures opens new avenues to structure refinement or determination, especially for condensed systems. PMID- 8502993 TI - Footprinting the sites of interaction of antibiotics with catalytic group I intron RNA. AB - Aminoglycoside inhibitors of translation have been shown previously to inhibit in vitro self-splicing by group I introns. Chemical probing of the phage T4-derived sunY intron shows that neomycin, streptomycin, and related antibiotics protected the N-7 position of G96, a universally conserved guanine in the binding site for the guanosine cofactor in the splicing reaction. The antibiotics also disrupted structural contacts that have been proposed to bring the 5' cleavage site of the intron into proximity to the catalytic core. In contrast, the strictly competitive inhibitors deoxyguanosine and arginine protected only the N-7 position of G96. Parallels between these results and previously observed protection of 16S ribosomal RNA by aminoglycosides raise the possibility that group I intron splicing and transfer RNA selection by ribosomes involve similar RNA structural motifs. PMID- 8502994 TI - New domain motif: the structure of pectate lyase C, a secreted plant virulence factor. AB - Pectate lyases are secreted by pathogens and initiate soft-rot diseases in plants by cleaving polygalacturonate, a major component of the plant cell wall. The three-dimensional structure of pectate lyase C from Erwinia chrysanthemi has been solved and refined to a resolution of 2.2 angstroms. The enzyme folds into a unique motif of parallel beta strands coiled into a large helix. Within the core, the amino acids form linear stacks and include a novel asparagine ladder. The sequence similarities that pectate lyases share with pectin lyases, pollen and style proteins, and tubulins suggest that the parallel beta helix motif may occur in a broad spectrum of proteins. PMID- 8502995 TI - Feedback regulation mechanisms for the control of GTP cyclohydrolase I activity. AB - Guanosine triphosphate (GTP) cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), is subject to feedback inhibition by BH4, a cofactor for phenylalanine hydroxylase. Inhibition was found to depend specifically on BH4 and the presence of another protein (p35). The inhibition occurred through BH4-dependent complex formation between p35 protein and GTP cyclohydrolase I. Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. These findings also provide a molecular basis for high plasma BH4 concentrations observed in patients with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency. PMID- 8502996 TI - Relation of phenotype evolution of HIV-1 to envelope V2 configuration. AB - Biological variability of human immunodeficiency virus type-1 (HIV-1) is involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Syncytium inducing (SI) HIV-1 variants emerge in 50 percent of infected individuals during infection, preceding accelerated CD4+ T cell loss and rapid progression to AIDS. The V1 to V2 and V3 region of the viral envelope glycoprotein gp120 contained the major determinants of SI capacity. The configuration of a hypervariable locus in the V2 domain appeared to be predictive for non-SI to SI phenotype conversion. Early prediction of HIV-1 phenotype evolution may be useful for clinical monitoring and treatment of asymptomatic infection. PMID- 8502997 TI - Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. AB - Activity-dependent synaptic plasticity in the superficial layers of juvenile cat and adult rat visual neocortex was compared with that in adult rat hippocampal field CA1. Stimulation of neocortical layer IV reliably induced synaptic long term potentiation (LTP) and long-term depression (LTD) in layer III with precisely the same types of stimulation protocols that were effective in CA1. Neocortical LTP and LTD were specific to the conditioned pathway and, as in the hippocampus, were dependent on activation of N-methyl-D-aspartate receptors. These results provide strong support for the view that common principles may govern experience-dependent synaptic plasticity in CA1 and throughout the superficial layers of the mammalian neocortex. PMID- 8502998 TI - Predisposition to neoplastic transformation caused by gene replacement of H-ras1. AB - Homologous recombination was used to introduce a nominally transforming mutation into an endogenous H-ras1 gene in Rat1 fibroblasts. Although both the mutant and the remaining normal allele were expressed equally, the heterozygous cells were not neoplastically transformed. Instead, spontaneously transformed cells arose from the heterozygotes at a low frequency, and the majority of these cells had amplified the mutant allele. Thus, the activated H-ras1 allele was not by itself dominant over the normal allele but predisposed cells to transformation by independent events, such as amplification of the mutant allele. PMID- 8502999 TI - Fruit fly aging and mortality. PMID- 8503000 TI - Fruit fly aging and mortality. PMID- 8503001 TI - Fruit fly aging and mortality. PMID- 8503002 TI - National Institutes of Health. Panel finds gaps in violence studies. PMID- 8503003 TI - Canadian blood inquiry. PMID- 8503004 TI - Forging a path to the nucleus. PMID- 8503005 TI - Magnetism triggers a brain response. PMID- 8503006 TI - The biological and social phenomenon of Lyme disease. AB - Lyme disease, unknown in the United States two decades ago, is now the most common arthropod-borne disease in the country and has caused considerable morbidity in several suburban and rural areas. The emergence of this disease is in part the consequence of the reforestation of the northeastern United States and the rise in deer populations. Unfortunately, an accurate estimation of its importance to human and animal health has not been made because of difficulties in diagnosis and inadequate surveillance activities. Strategies for prevention of Lyme disease include vector control and vaccines. PMID- 8503007 TI - Divergence in proteins, mitochondrial DNA, and reproductive compatibility across the isthmus of Panama. AB - It is widely believed that gene flow connected many shallow water populations of the Caribbean and eastern Pacific until the Panama seaway closed 3.0 to 3.5 million years ago. Measurements of biochemical and reproductive divergence for seven closely related, transisthmian pairs of snapping shrimps (Alpheus) indicate, however, that isolation was staggered rather than simultaneous. The four least divergent pairs provide the best estimate for rates of molecular divergence and speciation. Ecological, genetic, and geological data suggest that gene flow was disrupted for the remaining three pairs by environmental change several million years before the land barrier was complete. PMID- 8503008 TI - Structural basis of amino acid alpha helix propensity. AB - The propensity of an amino acid to form an alpha helix in a protein was determined by multiple amino substitutions at positions 44 and 131 in T4 lysozyme. These positions are solvent-exposed sites within the alpha helices that comprise, respectively, residues 39 to 50 and 126 to 134. Except for two acidic substitutions that may be involved in salt bridges, the changes in stability at the two sites agree well. The stability values also agree with those observed for corresponding amino acid substitutions in some model peptides. Thus, helix propensity values derived from model peptides can be applicable to proteins. Among the 20 naturally occurring amino acids, proline, glycine, and alanine each have a structurally unique feature that helps to explain their low or high helix propensities. For the remaining 17 amino acids, it appears that the side chain hydrophobic surface buried against the side of the helix contributes substantially to alpha helix propensity. PMID- 8503009 TI - A nonpeptidyl growth hormone secretagogue. AB - A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N (2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl) 1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone. PMID- 8503010 TI - Evidence of DNA bending in transcription complexes imaged by scanning force microscopy. AB - Complexes of Escherichia coli RNA polymerase with DNA containing the lambda PL promoter have been deposited on mica and imaged in air with a scanning force microscope. The topographic images reveal the gross spatial relations of the polymerase relative to the DNA template. The DNA appears bent in open promoter complexes containing RNA polymerase bound to the promoter and appears more severely bent in elongation complexes in which RNA polymerase has synthesized a 15-nucleotide transcript. This difference could be related to the conformational changes that accompany the maturation of open promoter complexes into elongation complexes and suggests that formation of the elongation complex involves a considerable modification of the spatial relations between the polymerase and the DNA template. PMID- 8503011 TI - DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing. AB - The concept of sequencing by hybridization (SBH) makes use of an array of all possible n-nucleotide oligomers (n-mers) to identify n-mers present in an unknown DNA sequence. Computational approaches can then be used to assemble the complete sequence. As a validation of this concept, the sequences of three DNA fragments, 343 base pairs in length, were determined with octamer oligonucleotides. Possible applications of SBH include physical mapping (ordering) of overlapping DNA clones, sequence checking, DNA fingerprinting comparisons of normal and disease causing genes, and the identification of DNA fragments with particular sequence motifs in complementary DNA and genomic libraries. The SBH techniques may accelerate the mapping and sequencing phases of the human genome project. PMID- 8503012 TI - Proliferation of human smooth muscle cells promoted by lipoprotein(a). AB - Elevated blood concentrations of lipoprotein(a) [Lp(a)] and its constituent, apolipoprotein(a) [apo(a)], constitute a major risk factor for atherosclerosis, but their physiological activities remain obscure. Lp(a) and purified apo(a) stimulated the growth of human smooth muscle cells in culture. This effect resulted from inhibition of plasminogen activation, and consequently the activation by plasmin of latent transforming growth factor-beta, which is an inhibitor of smooth muscle cell growth. Because smooth muscle proliferation is one of the hallmarks of atherosclerotic lesions, these results point to a plausible mechanism for the atherogenic activity of Lp(a). PMID- 8503013 TI - Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. AB - The guanosine triphosphate (GTP)-binding protein Ras functions in regulating growth and differentiation; however, little is known about the protein interactions that bring about its biological activity. Wild-type Ras or mutant forms of Ras were covalently attached to an insoluble matrix and then used to examine the interaction of signaling proteins with Ras. Forms of Ras activated either by mutation (Gly12Val) or by binding of the GTP analog, guanylyl imidodiphosphate (GMP-PNP) interacted specifically with Raf-1 whereas an effector domain mutant, Ile36Ala, failed to interact with Raf-1. Mitogen-activated protein kinase (MAP kinase) activity was only associated with activated forms of Ras. The specific interaction of activated Ras with active MAP kinase kinase (MAPKK) was confirmed by direct assays. Thus the forming of complexes containing MAPKK activity and Raf-1 protein are dependent upon the activity of Ras. PMID- 8503014 TI - Explaining fruit fly longevity. PMID- 8503015 TI - Explaining fruit fly longevity. PMID- 8503016 TI - Compositional interpretations of medfly mortality. PMID- 8503017 TI - Pathological evaluation of neoplasms with unknown primary tumor site. PMID- 8503018 TI - Genetic analysis in the diagnosis of neoplasms of unknown primary tumor site. AB - The identification of nonrandom chromosomal abnormalities in hematologic and solid tumor malignancies, which can serve as specific diagnostic markers, has permitted the application of cytogenetic techniques to the diagnosis of poorly differentiated carcinomas of unknown primary tumor site. Cytogenetic markers specific for germ cell tumors, neuroepithelial tumors, and lymphoma have now been identified in these patients. In the case of germ cell tumor diagnosis, the finding of a cytogenetic marker specific for germ cell cancer was predictive of responsiveness to cisplatin-based chemotherapy and long-term disease-free survival. DNA hybridization techniques, including quantitative Southern blot analysis and FISH, were also used to establish the diagnosis of germ cell tumor, particularly in the setting in which conventional cytogenetic analysis was unsuccessful. In poorly differentiated tumors in which conventional light microscopic, immunohistochemical, and electron microscopic techniques fail to yield a specific diagnosis, the use of molecular and cytogenetic markers in human malignancy promises to increase diagnostic acuity. These techniques have the potential to give clearer insight into the biology of this heterogeneous group of tumors and assist in directing appropriate therapy to patients who indeed may have a highly treatable disease. PMID- 8503019 TI - The biology of unknown primary tumors. PMID- 8503020 TI - Diagnostic evaluation of patients with carcinoma of unknown primary tumor site. PMID- 8503021 TI - Use of biological markers in the diagnosis of cancers of unknown primary tumor. PMID- 8503022 TI - Management of peritoneal carcinomatosis of unknown primary tumor site. PMID- 8503023 TI - Diagnosis and management of squamous cell carcinoma of unknown primary tumor site of the neck. AB - The development of metastatic carcinoma in cervical lymph nodes is a relatively common syndrome. In most patients, meticulous evaluation of the head and neck area and the lungs will identify a primary tumor site. FNA biopsy of the cervical lymph nodes is the recommended initial biopsy technique; open biopsy should be withheld until after a search for the head and neck primary tumor site is completed. In the patient with no identified primary tumor site, prognosis depends on the site and extent of neck involvement. Because comparative trials have not been performed, conclusions regarding optimal therapy must be made by inference from existing data. Patients with N1 disease located in the upper or midcervical lymph nodes have a relatively high cure rate and can usually be treated with a single local treatment modality (radiation therapy or radical neck dissection). Patients with N2 or N3 disease are probably best treated with combined local modalities including surgical resection followed by radiation therapy. Most investigators have recommended high-dose radiation therapy as is used to treat squamous cancer of the head and neck, with inclusion of those areas in the head and neck that may harbor an occult primary tumor site. Limited data exists regarding the benefit of systemic therapy added to local therapy in these patients. However, treatment with cisplatin and fluorouracil before definitive local therapy is reasonable in patients with N3 disease, who have very poor prognoses with local modalities alone. PMID- 8503024 TI - Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary tumor site. AB - Our understanding of this heterogeneous group of tumors continues to evolve. At present, clinicopathological observations, as well as conclusions regarding optimal therapy, are based on a small number of single-institution phase II studies. The exact incidence of PDC or PDA of unknown primary tumor site is unknown, as is the percent of highly treatable tumors contained within this group. However, the data collected to date allow several conclusions that greatly aid in the clinical management of these patients: 1. Patients in this group can usually be identified by light microscopy. Improved methods in diagnostic pathology have enabled more precise identification of a minority of tumors initially called PDC or PDA; therefore, immunoperoxidase staining should be routinely performed, and other techniques (electron microscopy and genetic analysis) should be performed on selected tumors. 2. Some patients with PDC or PDA have tumors that are highly responsive to cisplatin-based therapy. The number of potentially curable patients is unknown but is probably 5% to 15% of an unselected group. No reports have documented the curative potential of any noncisplatin-containing regimen; therefore, cisplatin-based regimens are the treatment of choice. The optimal cisplatin-based regimen is unknown, but the combination of cisplatin and etoposide (with or without bleomycin) has produced results at least as good as any other regimen. 3. Patients with responsive tumors have rapid objective responses; treatment can be discontinued after one or two courses in patients showing no response. No evidence exists that treatment for longer than four courses improves results in responsive patients. 4. By using several easily assessed clinical and pathological criteria, patients with a higher chance of responding to therapy can be identified. Favorable clinical features include tumor location in the retroperitoneum or peripheral lymph nodes, tumor limited to one or two metastatic sites, no smoking history, and younger age. Pathological evidence of a neuroendocrine tumor also identifies a responsive group. As more information accumulates, the diverse nature of the tumors in this group becomes more obvious. Although some responsive patients in this group have extragonadal germ cell tumors that are unrecognizable using standard pathological techniques, the majority of responders do not have clinical features suggesting this diagnosis. Likewise, no evidence exists to suggest that all responsive tumors belong to well-recognized groups of responsive tumors that could be identified by more careful or thorough pathological study. It is probable that future improvements in diagnostic pathology will result in better characterization of these tumors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8503025 TI - Poorly differentiated neuroendocrine carcinoma of unknown primary tumor site. PMID- 8503026 TI - Bone destruction in cancer. PMID- 8503027 TI - Clinical experience with strontium-89 in prostatic and breast cancer patients. AB - Bone metastases are a major problem in the clinical management of patients with breast or prostate cancer. Severe bone pain can be a particularly debilitating effect of metastatic disease, resulting in a growing dependency on opioid analgesics and a reduced quality of life in patients who have a short time to survive. The radiopharmaceutical strontium-89 has been demonstrated to be generally well tolerated as well as effective in reducing metastatic bone pain in breast or prostate cancer patients. Unlike other radioisotopes or external radiation treatments, it represents systemic, targeted therapy that is simple and fast to administer in an outpatient setting. Data accumulated over the last 15 years demonstrates that 89Sr provides pain relief in up to 80% of patients with bony metastases arising from breast or prostatic malignancies. Pain palliation is maintained for several months, along with improvements in functional status and quality of life. As many as one fifth of 89Sr-treated patients become pain free and require no further pain medication. The adverse effects of intravenous 89Sr are minimal. Bone marrow toxicity is observed in many patients, resulting in some reduction of platelet and white blood cell counts. Despite reductions of 20% to 30%, these hematologic effects are generally reversible and the majority of patients maintain platelet counts that are within normal limits. Strontium-89 is effective systemic radioisotopic therapy for the palliation of painful bony metastases from breast and prostate carcinoma. PMID- 8503028 TI - [Effect of stimulation of gigantocellulars reticular nucleus on the spontaneous and evoked activities of cerebellar Purkinje cells in the rat]. AB - In anesthetized and paralyzed rats, the effect of stimulation of Gigantocellulars Reticular Nucleus (Gi) on spontaneous and evoked simple spike discharges of cerebellar Purkinje cells (PCs) was examined. The result were as follows: (1) Stimulation of Gi elicited either inhibitory or excitatory effect on spontaneous simple spikes of PCs with latency less than 20 ms, being inhibitory in the most cases. The inhibitory responses lasted for 40-100 ms, while the excitatory ones were sometimes longer than 200 ms; (2) Injection of 5-HT2 receptor antagonist methysergide could reversibly attenuate or block the inhibitory effect of Gi stimulation on spontaneous simple spike discharges of PCs; (3) The evoked simple spike responses of PCs elicited by stimulating the contralateral cerebral sensorimotor cortex could be markedly suppressed or potentiated by the conditioning Gi stimulation. The results demonstrated that Gi-cerebellar pathways exists, with some fibers being serotonergic. Gi-cerebellar afferent fibers may have certain modulatory effects on PCs through synaptic and/or non-classical chemical synaptic transmission. The Gi-cerebellar afferent fiber projection may play important roles in some cerebellar functions, such as regulating myotonia and posture. PMID- 8503029 TI - [Effects of stimulation of SI cortex and cerebral peduncle on the nociceptive responses of spinal dorsal horn neurons in the rat]. AB - Single spinal dorsal horn neurons were recorded extracellularly with glass micropipettes, and the effect of stimulation of SI cortex or cerebral peduncle (CP) was observed on the long latency discharges (C-fiber evoked response) of the wide dynamic range (WDR) neurons induced by intense electrical skin stimulation. Inhibition was the predominant effect of SI cortex stimulation on the C-fiber evoked responses of WDR neurons. The effect of CP stimulation was similar to that of SI cortex stimulation, except that the former was much more effective than the latter. The inhibition lasted a period of time varying from 400 ms to more than 10 min after CP stimulation in different neurons. Systemic naloxone had no significant effect on the inhibition produced by CP stimulation. Systemic methysergide reduced or eliminated the inhibition in a part of the neurons tested, suggesting that 5-HT, but not opioid peptides, is involved partially in mediation of the descending inhibitory effect originating from the cortex. PMID- 8503030 TI - [Effects of microiontophoretically applied ACH and atropine on the electric activities of neurons in nucleus parafascicularis of thalamus in rats]. AB - The effects of acetylcholine (ACh) and atropine on the electric activities of neurons of nucleus parafascicularis thalami (Pf) were observed in anesthetized rats with multimicropipette technique and iontophoresis. It was found that the spontaneous and pain-induced discharges of the Pf neurons were excited and some of non-nociceptive neurons became sensitive to nociceptive stimulation with microiontophoretically applied ACh, while microiontophoretically applied atropine could diminish the spontaneous and pain-induced discharges of the Pf neurons. The effects of ACh above could be blocked by microiontophoretically applied atropine. The results show that ACh may have excitatory effects on the electric activity of the Pf neurons by M-receptor. PMID- 8503031 TI - [Effect of D1 and D2 dopamine receptor antagonists on acupuncture analgesia]. AB - Some highly selective D1 or D2 receptor antagonists were tested on rabbit skin pain model to investigate the effect of the subtypes of dopamine receptor on acupuncture analgesia. It was found that iv. of D2 receptor antagonists haloperidol and clozapine, had a potentiating effect on acupuncture analgesia. Icv. of D2 receptor antagonists domperidone and sulpiride and D1 receptor antagonist SCH23390 also enhanced acupuncture analgesia markedly. The effect of D1 and D2 receptor on acupuncture analgesia was discussed. PMID- 8503032 TI - [Changes in endocochlear potential induced by potassium-channel blockers]. AB - The effect of various potassium-channel blockers, 4-aminopyridine (4-AP), tetraethylammonium (TEA) and quinine, on the endocochlear potential (EP) was studied in perfused guinea pig inner ears. The fast K(+)-channel blocker, 4-AP, did not alter EP but changed its response model to intense noise exposure. While TEA and quinine significantly reduced the amplitude of negative component of EP (N-EP), comparing with a relatively smaller increase in general EP (G-EP). The results indicated the existence of different K(+)-channels with different physiological functions. PMID- 8503033 TI - [A study on the effect of stimulation of amygdaloid complex on the electrical response of auditory cortex in rabbits]. AB - Experiments were performed on 40 adult rabbits immobilized with Flaxedil. The effect of stimulation of amygdaloid complex on the click evoked potential of Woolsey's AI, AII and the auditory cortex behind the rhinal sulcus (ACBRS) was examined by single unit analysis. The results showed that stimulation of lateral nucleus and basal nucleus of amygdala could induce either a facilitory or an inhibitory effect on the evoked potential and the unit discharges. The latency of the inhibitory effect was about 10-25ms, and lasted for 20-115ms. A facilitory effect with a latency as short as 2ms was also observed in one animal. The experimental results indicate that the effect of amygdaloid complex stimulation as transmitted through polysynaptic circuit while the facilitatory effect was monosynaptic. The functional significance of the amygdaloid effect was discussed. PMID- 8503034 TI - [Responses of toad spinal ganglion neurons to repetitive stimulation of their central and peripheral processes]. AB - Intracellular recordings were made from 48 toad dorsal root ganglion neurons in vitro while electrical stimulation was delivered respectively to their dorsal root or sciatic nerve input. The average conduction velocities were respectively 12 m/s and 15 m/s. With progressively increasing frequency of stimulation, 30% of the recorded cells showed simultaneous decrease of amplitude, wave decomposition and dropping of propagated response to both inputs while 70% of the cells showed more or less different patterns of degradation of the various parameters. Complete failure of neurons to follow the inputs occurred respectively at 126 and 323 Hz. Evidently the dorsal root ganglion neurons reported in the present work pertain to type A neuron with central processes smaller in diameter than peripheral ones A possible mechanism underlying the different changes is discussed. PMID- 8503035 TI - [Effect of hypoxia on membrane potential and input resistance of cultured carotid body glomus cells in rat]. AB - Carotid bodies were removed from rats (50-100 g) under sodium pentobarbitone anesthesia and dissociated by mechanical means to obtain small clusters and single glomus cells to be cultured under normoxic (5% CO2, 20% O2, 75% N2, 37 degrees C) or hypoxic (5% CO2, 10% O2, 85% N2, 37 degrees C) conditions for 3-5 days. They are respectively called normoxic or hypoxic cells. The membrane potential (MP) and input resistance (Ri) of the normoxic cells were measured under normoxic condition as controls. The results show that MP of the normoxic cells measured under hypoxic condition increased in about half the cells and decreased in an other half. The percentage of cells with increased MP was higher under 100% N2 than under hypoxia. The MP and Ri of the hypoxic cells measured under normoxia were not significantly different from the control values, but the MP and Ri of the hypoxic cells measured under hypoxia were significantly higher than those of the control (MP: P < 0.01, Ri: P < 0.05). The results suggest that oxygen sensing of the carotid body is reflected by changes in MP and Ri of the glomus cells. PMID- 8503036 TI - [Temporal phase complementarity between the lateral geniculate neurons sharing a common receptive field]. AB - Bi-unit recordings were sometimes obtained in the lateral geniculate nucleus of cat with a single microelectrode. The neuron pairs consisted of an on-center and an off-center cell sharing a common receptive field and both cells showed either transient or sustained responses to light stimulation. When a sinusoidally modulated light spot was presented at their receptive field center, the on-center and off-center cells responded half a cycle (approximately 180 degrees) out of phase with one another at all intensities tested. At a low temporal frequency (5 Hz), peak responses occurred in response to the maximum (in on-center cells) or minimum (in off-center cells) luminances of light modulation with an identical delay. The complementary phase property makes the cell couple work in a "push pull" manner and enables transient cells, which show half-cycle rectification as they work alone, to transmit modulated light signals of complete cycle. PMID- 8503037 TI - [The responses of phrenic discharges to microinjection of morphine and naloxone into central nucleus amygdala in rabbits]. AB - Experiments were done on 24 urethan anesthetized (20%, 1 g/kg), vagotomized and spontaneously breathing rabbits (2-3 kg). The effects on phrenic activity by microinjection of morphine and naloxone into central nucleus amygdala (ACE) were observed. The main results were as follows: (1) Injection of morphine resulted in two respiratory effects, firstly a marked increase in inspiratory time (Ti) and amplitude of phrenic activity (AMP) with little changes of respiratory frequency (RF), and secondly a significant decrease in AMP with little changes in Ti. (2) Injection of naloxone resulted in increases in RF, AMP and decreases in Ti with no marked changes in blood pressure. (3) Prolongation of inspiratory time by morphine can be blocked by previous injection of naloxone. The results suggested that endogenous morphine in ACE have different effects on respiration mediated by different receptor. PMID- 8503038 TI - The lactose permease of Escherichia coli: a paradigm for membrane transport proteins. PMID- 8503039 TI - Dimerization of glycophorin A transmembrane helices: mutagenesis and modeling. PMID- 8503040 TI - Effects of nucleotide binding fold mutations on STE6, a yeast ABC protein. PMID- 8503041 TI - The evolution of membrane carriers. PMID- 8503042 TI - Molecular characterization of the erythrocyte chloride-bicarbonate exchanger. PMID- 8503043 TI - The cardiac sodium-calcium exchanger. PMID- 8503044 TI - Function and biosynthesis of erythroid and nonerythroid anion exchangers. PMID- 8503045 TI - Mitochondrial carrier family: ADP/ATP carrier as a carrier paradigm. PMID- 8503046 TI - The sodium/glucose cotransporter (SGLT1). PMID- 8503047 TI - Gene fusion approaches to membrane protein topology. PMID- 8503048 TI - Structure and function of sodium-coupled neurotransmitter transporters. PMID- 8503049 TI - The Na+/I- symporter of the thyroid gland. PMID- 8503050 TI - Electrophysiology of the Na+/glucose cotransporter. PMID- 8503051 TI - Tails of serotonin and norepinephrine transporters: deletions and chimeras retain function. PMID- 8503052 TI - Identification of a new family of proteins involved in amino acid transport. PMID- 8503053 TI - The high-resolution three-dimensional structure of a membrane protein. PMID- 8503054 TI - Insights into membrane protein folding and translocation from the behavior of bacterial toxins: models for membrane translocation. PMID- 8503055 TI - Reconstitution of human erythrocyte band 3 into two-dimensional crystals. PMID- 8503056 TI - University students' intention to seek medical care promptly if symptoms of sexually transmitted diseases were suspected. AB - The aim of this study was to identify the factors explaining intention to seek medical care promptly if STD symptoms were suspected. A random sample of 1617 undergraduate students completed a questionnaire assessing intention, attitude, perceived norm among friends, perceived behavioral control, and risk of disease, along with different socio-demographic variables. The regression of intention on all variables yielded an adjusted R2 of 0.32 (P < 0.0001). The factors explaining this variance were the perceived advantages, easiness, and social norm among friends regarding seeking medical care promptly, age, and gender. Perception of risk to delay seeking medical care and perceived personal risk of getting STDs were not significant variables. Overall, the results indicate the need to develop programs for male first-year students. These programs will have to influence the attitude, that is, the perceived advantages of seeking medical care promptly if STD symptoms are suspected. Seeking advice from students' friends, and perception of these friends as a significant reference source if STD symptoms are suspected, should also be promoted. PMID- 8503057 TI - Persistence of multiple serovars of Neisseria gonorrhoeae. AB - Two simple mathematical models of gonococcal transmission dynamics that allow for heterogeneity within the pathogen were assessed. Models were compared for their ability to mirror the observed persistence of different gonococcal serovars over time and differential distribution within subgroups of the total population. Serotyping data collected between the periods of 1984-1988 and 1988-1990 were analyzed for differences in serovar distribution. The data show persistence of multiple serovars within both homosexual and heterosexual contact groups over time. The models provide a framework for the use of phenotypic markers to assess behavior change in sexually active populations. PMID- 8503058 TI - The origin of syphilis. Clinical and epidemiologic considerations on the Columbian theory. AB - It is an unpleasant vogue of our day to soil the image of outstanding personalities. Christopher Columbus is blamed for the crimes and cruelties that were committed in the New World after his landing in San Salvador as well as for the import of syphilis from West India to Europe. Attempts to trace the origin of the pandemic of syphilis at the verge of the fifteenth century concluded with the myth that the disease was contracted in Haiti by members of Columbus' crew who later joined the army of Charles VIII of France and participated in the siege of Naples. The surrender of the town on February 22, 1495, at 4 pm (natal hour of syphilis) was followed by orgies, which led to infection of all participants, particularly of all soldiers, who then spread the disease on their journey back to France. This story is refuted on the ground of epidemiologic and clinical facts. Most of the crew of Columbus' first trip joined the admiral in his second expedition, too, left Europe on February 24, 1494, and did not return before June 11, 1496 (87 days, or 12.4 weeks). With not more than approximately 10 persons arriving in Naples for such a short stay, an endemic of syphilis of such grave proportions could not have occurred. The disease has an incubation period of 4 weeks and a contagiosity rate of approximately 30%. In addition, 2 years and 47 days had passed between the departure from Haiti and the arrival in Naples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503059 TI - Sexually transmitted disease diagnostics initiative. PMID- 8503060 TI - Antibodies to Chlamydia species in patients attending a genitourinary clinic and the impact of antibodies to C. pneumoniae and C. psittaci on the sensitivity and the specificity of C. trachomatis serology tests. AB - In a retrospective study, the prevalence of antibodies to Chlamydia trachomatis serovars D to K, C. pneumoniae, and C. psittaci in cases attending a genitourinary clinic was examined. Blood samples were collected from 7,002 cases attending the clinic in Doncaster, England between May 1983 and May 1990. Sera from these samples were tested by a modified microimmunofluorescence test using panels of microdots of egg-grown, purified elementary bodies representing a pool of C. trachomatis D to K, a single C. pneumoniae agent, a single C. psittaci agent, and a negative control. Serum specimens were tested for the presence of IgG and IgM at starting dilutions of 1/16 and 1/8, respectively. Chlamydial IgG at a level of 1/16 or higher and IgM at a level of 1/8 or higher was present in 66.6% and 2.6% of samples, respectively. Species-specific or cross-reactive IgG against C. trachomatis D to K, C. pneumoniae, and C. psittaci was present in 32.6%, 25.1%, and 0.1% of the samples, respectively. In 8.7% of samples, the level of IgG was similar against two or all three species (group-specific). IgM against C. trachomatis D to K, C. pneumoniae, or C. psittaci was present in 2.5%, 0.03%, and 0.04% of the samples, respectively. The results of the study show that antibodies to C. pneumoniae and C. psittaci account for up to half of all chlamydia IgG positive cases attending genitourinary clinics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503061 TI - High syphilis rates among cocaine abusers identified in an emergency department. AB - The recent syphilis epidemic in the United States has been linked to cocaine abuse. The goal of this study was to estimate the prevalence of newly diagnosed latent syphilis, as well as previously treated syphilis, in emergency department patients giving a history of cocaine use. Charity Hospital emergency department patients without symptoms of sexually transmitted disease (STD) who admitted to cocaine use were enrolled and screened for syphilis with the automated reagin test (ART). Patients were questioned about past syphilis episodes, sexual behavior, and drug use patterns. Reactive ARTs were confirmed with the microhemagglutination antibody to Treponema pallidum (MHA-TP) or the fluorescent treponema antibody-absorbed (FTA-ABS) test. Additionally, treponemal tests were performed in 68 of 79 ART-negative patients. Twenty-four women and 78 men were included in the sample over the 6-month period from December 1989 through May 1990. Of those enrolled, 64% used crack, only 24% were exclusively intravenous users, and 6% were exclusively nasal users. The remaining 6% utilized multiple routes of drug administration. Nine latent syphilis patients (8.8%) were diagnosed and an additional 20 (19.6%) patients were found to have had previous syphilis. Among the 24 women studied, 5 (20.8%) had latent syphilis. Fifty-eight percent of women had either latent or previously treated syphilis as compared to 19% of men (P = 0.0006). These data suggest that elicitation of a history of cocaine use from urban hospital emergency department patients may be helpful in identifying patients with latent syphilis. Detection and treatment of latently infected women in this setting could prevent a significant number of congenital syphilis cases. PMID- 8503062 TI - The effect of video interventions on improving knowledge and treatment compliance in the sexually transmitted disease clinic setting. Lesson for HIV health education. AB - Eight intervention studies investigating patient education and treatment adherence in the sexually transmitted disease (STD) clinic setting are reviewed. Across the eight studies selected for analysis, meta-analytic procedures were applied to compare the impact of educational and prevention approaches. The effect of video was compared with that of other modes of health education on: 1) knowledge and attitudes about STDs and condoms and 2) treatment compliance, as measured by return for test of cure, drug compliance, premature resumption of sexual activity, and condom coupon redemption rates. The largest effects were those for video on knowledge and attitudes about STDs and condoms, followed by the effects of other non-video interventions on STD knowledge. Lower effects were found among video and non-video interventions targeting treatment compliance outcomes. These results are consistent with prior prevention studies that have demonstrated difficulty in achieving behavior change. PMID- 8503063 TI - Herpes revisited. Still a cause of concern. AB - The American Social Health Association (ASHA) surveyed people with herpes about their experiences with the disease and its effect on their lives. A systematic sample of 5,000 was chosen from approximately 10,000 readers of the helper, ASHA's quarterly journal for people with herpes. Of the sample, 3,120 returned completed surveys, which addressed medical history, health-care experience, treatment, personal impact, and demographic information. Data analysis was descriptive, consisting of observed frequencies and cross-tabulations. Data illustrated that the psychosocial impact of herpes can be serious and long lasting. Diagnosis is often associated with emotional upheaval, and dissatisfaction with diagnosing health-care providers was common. Over one-half of the respondents reported feelings of depression and fear of rejection in the last year. Sexual enjoyment and activity also were negatively affected by herpes. These results may be instructive to those delivering health services by providing insight into the significant impact of herpes on those infected. PMID- 8503064 TI - Use of condoms by heterosexually active drug abusers before and after AIDS education. AB - This study identified variables associated with increased condom use among drug abusers in a randomized trial of three AIDS educational programs in a short-term inpatient detoxification program. Participants (n = 301) completed baseline and follow-up interviews and were heterosexually active on both occasions. At baseline, 10% always, 24% sometimes, and 66% never used condoms, and this distribution changed only slightly at follow-up. Among the latter two groups, 21% increased their use. There was no differential intervention effect on changes in condom use. Women, but not men, were more likely to initiate condom use than to increase to consistent use with all partners, and to initiate use if they had multiple partners. Although beneficial attitudes and beliefs about condoms were more common among women at baseline, positive changes in these attitudes/beliefs were associated with increased condom use among men only. Among men, personal attitudes and beliefs were associated with increased condom use, while among women, perceptions of the attitudes of sexual partners were more important. PMID- 8503065 TI - Early syphilis. Relationship to sex, drugs, and changes in high-risk behavior from 1987-1990. AB - A case-control study was conducted to evaluate two main questions: 1) which specific sex- and drug-use behaviors are associated with the acquisition of early syphilis; and 2) whether changes in sex- and drug-use behaviors from 1987-1990 associated with acquisition of early syphilis. Risk factors associated with significant odds ratio were greater than four sex partners and lack of condom use in the past 3 months. Crack use within the past 3 months was the only specific drug-related risk factor with a significantly elevated odds ratio. However, a number of risk factors associated with both sex and drugs had significantly elevated odds ratios: number of drug-using partners, number of partners exchanging sex for drugs and money, and number of partners with whom the respondent shares sex and drugs. Risk estimates for early syphilis were uniformly higher for women as compared with men. Women appeared to be at higher risk of syphilis than men when engaged in the same high-risk activities. From 1987-1990, there was a significant change from lower-risk to higher-risk behaviors among patients. Patients showed an increase in their number of sex partners, in drug use, and in other high-risk activities. Increasing rates of syphilis can be attributed to a particular set of sex- and drug-related behaviors, and an increase in the adoption of these behaviors has probably contributed significantly to the increased rate of early syphilis in Trenton, NJ, during the period from 1987-1990. PMID- 8503066 TI - The use and physical effects of intravaginal substances in Zairian women. AB - Women in Kananga, Zaire, sometimes insert substances into the vagina to enhance sexual pleasure. The objective of this study was to ascertain: 1) what intravaginal substances are used, 2) the prevalence and frequency of their use, and 3) the visible effects they produce on the female genitalia. Focus group discussions with women and men were conducted, and both prostitutes and non prostitutes were interviewed individually about their sexual preferences and practices. The cervices and vaginae of eight women were inspected and photographed before and after the insertion of commonly used substances. It was found that Kananga residents preferred a "dry-tight" vagina during coitus. They named thirty substances (leaves and powders) that women insert to produce this sensation. Twenty-one of 50 prostitutes (42%), and 17 of 49 non-prostitutes (35%), had used such intravaginal substances. Inspection of the genitalia showed that five different leaves produced inflammatory reactions that lasted up to a week. These genital irritations might facilitate the transmission of pathogenic organisms. Investigators elsewhere should study the use of intravaginal substances and their relationship to sexually transmitted diseases. PMID- 8503067 TI - Laparoscopic herniorrhaphy: where goest thou? PMID- 8503068 TI - Laparoscopic hernia repair: a plea for science and statistics. PMID- 8503069 TI - Hans Kehr: not first, but foremost. PMID- 8503070 TI - Complications of laparoscopic herniorrhaphy. AB - Anterior inguinal hernia repair is the second-most-commonly performed abdominal operation and has been associated with low morbidity and mortality rates. The principle of laparoscopy has been applied to this surgical problem in a series of 762 patients with 841 inguinal hernias. Four types of laparoscopic repairs were conducted: (1) high ligation of the indirect inguinal hernia sac and closure of the internal ring (87 patients with 89 hernias); (2) plug and patch of the internal ring (74 patients with 87 hernias); (3) transperitoneal suture repair of the transversalis fascia to the iliopubic tract or Cooper's ligament (28 patients with 30 hernias); and (4) placement of a large prosthesis over the myopectoneal orifice (563 patients with 635 hernias). These early results indicate that the overall complication rates were low, especially when a large prosthesis was used to reinforce the myopectoneal orifice. It is concluded that laparoscopic inguinal herniorrhaphy is a safe and effective procedure with which to manage this surgical problem. PMID- 8503071 TI - Laparoscopic preperitoneal inguinal hernia repair without peritoneal incision. Technique and early clinical results. AB - More than 500,000 hernia procedures are performed annually in the United States alone. The authors have devised a new technique for laparoscopic hernia repair. The peritoneum is not incised, as the space between the abdominal wall and the peritoneum is developed with CO2 and blunt dissection. The trocars and laparoscope are placed within this preperitoneal space. Mesh is stapled to Cooper's ligament and the underside of the abdominal wall. From November 1990 to January 1992, 68 herniae have been repaired in 35 patients. The first 25 patients were kept overnight for observation and discharged the following day. Thirty-two patients (92%) were able to resume full physical activity within 1 week. Average follow-up was only 12 months, but there were no recurrent or retained herniae. PMID- 8503072 TI - Laparoscopic hernia repair. AB - In this study, 101 consecutive laparoscopic transabdominal preperitoneal hernia repairs (LTPR) were performed in 62 patients by a single surgeon. The series began in April 1991 and involved repair of 49 direct, 41 indirect, 4 femoral, 3 umbilical, 3 sliding, and 1 incisional hernias. Twelve cases were bilateral, 11 hernias were incarcerated, and 15 hernias were recurrent. There were no intraoperative complications, and none of the procedures required conversion to open surgery. Patients experienced the following postoperative complications: transient testicular pain (1), transient anterior thigh paresthesias (2), urinary retention requiring TURP (1), and hernia recurrences (2). Follow-up has ranged from 6 to 17 months and initial results have been encouraging. PMID- 8503073 TI - Diagnostic laparoscopy in the intensive care patient. Avoiding the nontherapeutic laparotomy. AB - Evaluation of a potential acute abdomen in patients who require intensive care for concurrent medical/surgical problems is often difficult due to ambiguities in the physical exam and ancillary diagnostic tests. Between August 1990, and February 1992, 25 ICU patients underwent diagnostic laparoscopy to evaluate a suspected acute intraabdominal process. Thirteen laparoscopies were negative, and 12 were positive. The overall accuracy for laparoscopy was 96% as confirmed by subsequent laparotomy, autopsy, or clinical course. Laparoscopic findings led to a change in management in nine patients (36%), leading to earlier exploration in four patients, and avoidance of laparotomy in five. No significant hemodynamic effects were noted during laparoscopy, and the procedure-related morbidity was low (8.0%). Diagnostic laparoscopy is a safe and accurate guide for managing the ICU patient with a suspected acute surgical abdomen. The use of laparoscopy can help avoid nontherapeutic laparotomy or confirm the need for operative intervention in these complex cases. PMID- 8503074 TI - Early experience of laparoscopic ultrasonography in the management of pancreatic carcinoma. AB - A 7.5-MHz linear array ultrasound probe has been developed for the evaluation of solid organs at laparoscopy. Twelve patients with suspected carcinoma of the head of the pancreas, considered at initial investigation to have resectable disease, were submitted to laparoscopy. In 4 patients, diagnostic laparoscopy revealed hepatic metastases (4 patients), peritoneal dissemination of tumor (2), and malignant ascites (1). Laparoscopic ultrasonography demonstrated hepatic metastases in four patients and hepatic cysts in two further patients. Ultrasound evaluation of the pancreas revealed lymphadenopathy (4 patients), local infiltration (2), and portal vein displacement or invasion (4). An anomalous right hepatic artery arising from the superior mesenteric artery was identified in one patient. Overall, laparoscopy identified advanced disease in four patients. Laparoscopic ultrasonography, while detecting advanced disease in a further two patients. predicted resectable disease in six patients (50%). Only one of the six patients submitted to laparotomy was found to have irresectable disease due to lymph-node metastases. Laparoscopic ultrasound examination of the pancreas and liver has improved the early staging of pancreatic carcinoma and should be undertaken at an early stage in the management of such patients. PMID- 8503075 TI - Intraoperative ultrasound guidance for hysteroscopic retrieval of intrauterine foreign bodies. AB - Retained bony fragments after a therapeutic abortion represent a rare complication of this gynecologic procedure. Management has been previously described to include blind dilatation and curettage, hysterectomy, and in select cases and with variable success, hysteroscopy. We describe a case of retained bones after a second-trimester abortion managed by operative hysteroscopy using a resectoscope and wire loop under intraoperative transabdominal ultrasound guidance. PMID- 8503076 TI - Adenomyoma of the stomach. Report of a case and review of the literature. AB - A case of adenomyoma of the prepyloric antrum and a review of the previous reported in the literature are presented. The tumor is composed of cysts and glandular structures lined by cuboidal-to-columnar epithelium surrounded by hypertrophic smooth muscle bundles. Furthermore, glands resembling Brunner's and/or heterotopic pancreatic tissue are present in some patients. The endoscopic characteristics of the lesion are discussed, as well as the diagnostic and therapeutic approaches. PMID- 8503077 TI - Ancillary colonoscope insertion techniques. An evaluation. AB - Colonoscope insertion from anus to cecum requires a sound basic technique that minimizes looping and maintains a straight scope. Four adjunct techniques may help advance insertion but none has been carefully evaluated. Accordingly, data were collected prospectively from 417 patients undergoing colonoscopy by the author. There were 223 males and 194 females with a median age of 60 years (range 12-94 years). Colonoscopy was complete in 405 cases (97.1%). The incidence and effectiveness of the four maneuvers were: hold breath (63%, 32%), abdominal pressure (65%, 60%), turn on left side (36%, 42%), turn on right side (19%, 77%). All 4 techniques were used in 54 patients (13%); 3 were used in 98 (24%); 2 in 98 (24%); 1 in 53 (13%); and none in 114 (27%). These ancillary techniques were more often used in females than males (P = 0.01); in intact colons more often than those after left colectomy (P = 0.001); and in patients of slim build than those of normal build (P = 0.04). Of the four techniques, abdominal pressure was most often used and turning on the right side was most often effective. PMID- 8503078 TI - Laparoscopic intraperitoneal intestinal anastomosis. PMID- 8503079 TI - Endoscopic ultrasonic dissection for thoracoscopic and laparoscopic surgery. AB - A specifically designed handpiece has been developed for ultrasonic dissection of tissues and organs during minimal-access surgery. The experimental prototype has been evaluated in major endoscopic operations on the esophagus, colon, and rectum (n = 19). The benefits documented by this initial experience include increased dissection efficiency of extensive fibroareolar attachments, safe exposure of major vascular pedicles (especially those located in mesocolic fat), greatly reduced risk of major hemorrhage, and decreased operating time. PMID- 8503080 TI - A new flexible videoendoscope for minimal access surgery. AB - This study was designed to evaluate the efficacy of a new flexible videolaparoscope. The Fujinon EVL-F has standard control knobs which deflect a flexible tip at the end of a rigid section. In addition, there are standard controls for irrigation and suction as well as an instrument channel. Twenty eight procedures were performed on 22 patients. The advantages of this instrument include the ability to perform a more thorough exploration of the abdomen and improved image quality. In addition, the instrument channel provides the capability to irrigate, suction, perform cholangiograms, or pass dissecting instruments via the laparoscope, thus reducing the required number of trocar sites. PMID- 8503081 TI - Virtual reality surgical simulator. The first steps. AB - The virtual-reality surgical simulator signals the beginning of an era of computer simulation for surgery. The surgical resident of the future will learn new perspectives on surgical anatomy and repeatedly practice surgical procedures until they are perfect before performing surgery on patients. Primitive though these initial steps are, they represent the foundation for an educational base that will be as important to surgery as the flight simulator is to aviation. It is anticipated that the full development of the surgical simulator will take less than the 40 years which was required for flight simulators to become an indispensable ingredient of pilot training. As the system evolves, many new and yet-to-be-imagined applications will arise, but we must have understanding and patience as we wait for computer power to improve to a point where VR surgical simulation can emerge from its PacMan era. PMID- 8503082 TI - Accuracy of laparoscopic cholecystectomy data. PMID- 8503084 TI - Laparoscopic insertion of prosthetic mesh. PMID- 8503083 TI - Choice of procedure in patients with "acid antrum". PMID- 8503085 TI - Gallstones and laparoscopic cholecystectomy. NIH Consensus Development Panel on Gallstones and Laparoscopic Cholecystectomy. PMID- 8503086 TI - [Potentialities and limitations of combined radiotherapy-surgical treatment of large orofacial T3/T4 tumors]. AB - The possibilities, limits and good cosmetic and functional results of combined radiotherapy-surgical treatment of large orofacial tumors (T3) are prescribed. The pre- and postoperative split radiotherapy with operation in between is favoured. The radical en-bloc-resection with radical neck dissection is the surgical therapy of choice. The defects have been reconstructed with osteomusculocutaneous flaps. PMID- 8503087 TI - [Clinical and radiation physics studies on the influence of mandibular reconstruction plates on the dose distribution of ultrahard photons]. AB - The effect of mandibular reconstruction plates on the dose distribution of megavoltage photons was analysed. All treated patients showed the normal reactions expected from radiation therapy regardless the modification of dose distribution by the metal plates. For dose estimation measurements were done in a phantom with photons of the energy 60Co to 42 MV and different material. PMID- 8503088 TI - Lymphangiosarcoma of arm after chronic lymphedema: a rare long-term complication after radical mastectomy in breast cancer patients. Case report and overview. AB - Lymphangiosarcoma after mastectomy was first described by Stewart and Treves in 1948. Today, this tumor associated with chronic lymphedema has become a rare entity, due to less radical surgery. Chronic lymphedema and lymphangiectasia of limbs preceding lymphangiosarcoma may not only be induced by radical mastectomy. Also post-traumatic, congenital, filarial-associated or spontaneous chronic lymphedema may be associated with lymphangiosarcoma. A time interval of years seems to be required before malignant changes supervene and lymphangiosarcoma develops. This paper describes a case with lethal and arising in an edematous arm years after radical mastectomy and irradiation. Current concepts of etiology, histopathology, immunohistology, diagnostic investigation, treatment and prognosis are presented. PMID- 8503089 TI - [A quality assurance program for simulators in radiotherapy. 1: The universal phantom for quality control of therapy simulators and teletherapy equipment]. AB - A new phantom is described which shall be utilized to check geometric parameters of simulators and therapy units. Because of its mechanical assembly technique construction it is possible to use any part of the system fixed on a base plate which has to be adjusted only once. The application of the different parts of the phantom will be illustrated by some check examples on simulators and linacs. An intercomparison of quality control data referring to therapy simulators in various centres of South Germany has been started whereby the usability and reliability of the phantom also will be tested. The preliminary results give objective reasons for its suitability to study generally the performance tolerances of simulators with regard to quality assurance in radiotherapy. PMID- 8503090 TI - Computer simulation of fractionated radiotherapy: further results and their relevance to percutaneous irradiation and brachytherapy. AB - Based on previous papers, the present communication considers the simulation of the radiotherapeutic treatments of glioblastoma multiforme, rectum adenocarcinoma, and gynaecological tumors of cervix uteri (squamous and adenocarcinoma) in spheroid culture. Starting with a single tumor cell in a nutrient medium and after the corresponding growth of the tumor spheroids, varying irradiation schemes are applied to the carcinoma and are compared with regard to tumor kill effectiveness using the LQ-model. The two first-mentioned carcinoma are exposed to the dose fractionation schemes standard-, super-, hyperfractionation, and weekly high single dose. The result is that hyperfractionation (3 x 1.5 Gy/day) and weekly high single dose (1 x 6 Gy/week) yield the most effective tumor cell kill. The weekly high single dose may be realized by some different irradiation techniques, e. g. stereotactic irradiation or interstitial high dose rate brachytherapy. The treatment of the cervix uteri tumors is performed by a combined therapy form (high dose rate brachytherapy and percutaneous irradiation). A comparing simulation of two typical regimens yields a nearly equivalent tumor kill effectiveness. By the integration of in vitro tumor growth and clinical treatment schemes in a computer model, the possibility is made available to test the effectiveness of variable regimens with the help of computer experiments. PMID- 8503091 TI - Cholinesterase response in the rhabdomyosarcoma tumor and small intestine of the BALB/c mice and the radioprotective actions of exogenous ATP after lethal dose of neutron radiation. AB - The rhabdomyosarcoma tumors were subjected to different doses of 2.0, 3.8 and 7.0 Gy from a neutron beam facility p(66 MeV)/Be. Elevated levels of cholinesterase activity are observed in which there is a correlation between the different doses of neutron radiation and the augmentation response of this enzyme. The increase of cholinesterase activity after 7 Gy neutron irradiation as a feature of involvement in the homeostatic mechanism maintaining the proper choline/acetylcholine ratio in the cell is also observed at 1 and 24 h in both tissues, rhabdomyosarcoma and small intestine. The activity of the enzyme after neutron irradiation with prior administration of ATP showed smaller increases when compared with increases observed after neutron irradiation alone. Moreover in the present work the protective mechanism of ATP in the response of cholinesterase activity is marked differential between both, normal and tumoral tissue and correlated inversely with the administered of the following concentrations of exogenous ATP (8, 25, 80, 250, and 700 mg/kg body weight) prior to exposure to 7 Gy neutron radiation. These results reflect the radioprotective ability of exogenous ATP to exert a number of metabolic adaptations as a defense mechanism in which the cell exposed to neutron radiation could remain viable because the injury is potentially repairable. PMID- 8503092 TI - Two different types of cell loss patterns of murine tumors and their corresponding histological findings and possible mechanisms of production of hypoxic cells. AB - Cell loss patterns of five tumors and their histological findings were investigated in WHT/Ht strain mice. The tumors investigated were squamous cell carcinoma H, squamous cell carcinoma NOS, squamous cell carcinoma TAK, rhabdomyosarcoma KAS, and fibrosarcoma YAS. The present study revealed that histological findings of tumor tissues are not necessarily corded structure presented by Thomlinson and Gray. The five were divided into two groups according to their histological findings, i.e. a corded structure (squamous carcinoma H and NOS) and a non-corded structure (squamous cell carcinoma TAK, rhabdomyosarcoma KAS and fibrosarcoma YAS). The cell loss patterns (125I-iododeoxyuridine retention curves) were also divided into two groups which corresponded to the histological structures. Two tumors with the corded structure (squamous cell carcinoma H and NOS) have a cell loss pattern with a constant shoulder portion (a migration time of tumor cells through a tumor cord from capillary to necrotic region). In these tumors, the cell loss occurred in the necrotic regions. In the other tumors with the non-corded structure, cell loss curves have no constant shoulder portion and cell loss might occur throughout the tumor. The origin of hypoxic cells in these two types of histology are presumably different. The diffusion-limited hypoxia, i.e. chronically hypoxic cells, may be the main cause for the tumors with corded structure. On the other hand, hypoxia as a result of temporary cessation of blood flow within the tumor vasculature, i.e. acutely hypoxic cells, may mainly occur in the tumor with non-corded structure. PMID- 8503093 TI - Copperglycinate protects mice exposed to various doses of gamma radiation. AB - Mice administered with various doses of copperglycinate (= glycine copper complex = GC) 15 min before exposure to various doses of gamma radiation showed an increased survival as compared to the non-drug treated irradiated control. It was also observed that 750 mg/kg body weight of GC was superior to the 500 and 1000 mg/kg body weight of GC as is evidenced by higher number of survivors in this group. The free radical scavenging activity of GC increased linearly with increasing drug dose. PMID- 8503094 TI - Influence of age and salivary secretion rate on oral sugar clearance. AB - The influence of age and salivary flow on oral sugar clearance was studied. Saliva was sampled with small circular paper discs, absorbing a certain amount of saliva. Glucose concentration was analysed enzymatically. Salivary glucose clearance was estimated in: (i) children of various ages and adults, (ii) hospitalised elderly patients, elderly people living at home and middle-aged adults, and (iii) elderly individuals with various types of prosthodontic reconstructions. Furthermore, an experimental model with pharmacologically reduced salivary flow was used to evaluate the relationship between salivary glucose clearance and salivary flow, also taking into consideration pH changes in dental plaque and the sugar intake concentration. In addition, an attempt to speed up prolonged oral sugar clearance in a group of hospitalised elderly patients was made with an individual programme. The main findings were that 3 year-olds exhibited higher salivary glucose concentration levels and greater variations in glucose clearance between different food products than older children and adults. Elderly people, especially hospitalised patients, cleared sugar from the oral cavity less effectively than young and middle-aged adults. Removable dentures, particularly complete dentures, contributed to higher salivary sugar concentration in elderly people. Higher glucose levels in saliva and more pronounced pH drops in dental plaque were obtained at low than at normal salivary flow. There was a bi-linear relationship between salivary glucose clearance sublingually and salivary secretion rate. Small changes in salivary flow below the border line values--which correspond to the intersection between the two phases--resulted in relatively large differences in clearance. It was possible to speed up prolonged oral sugar clearance in hospitalised elderly patients by using an individual training programme. To conclude, oral sugar clearance was comparatively slow in young children and in hospitalised elderly patients. A low salivary secretion rate was found to affect oral sugar clearance negatively. PMID- 8503095 TI - Human and experimental osteoarthrosis of the temporomandibular joint. Morphological and biochemical studies. AB - Osteoarthrosis is a common disease of the temporomandibular joint. The frequency and sites of location were studied in autopsies and they were classified according to age, sex and state of dentition. There was no differences related to sex, but the osteoarthrotic lesions were more severe and frequent in joints of specimens from subjects of high age without teeth of their own. The single most affected joint component was the disk which may be due to a limited regenerative ability of this joint component. The glycosaminoglycans of the extracellular matrix of human, osteoarthrotic disks were examined by high-performance liquid chromatography and compared to normal controls. The total glycosaminoglycan content of the arthrotic disks was lower whereas the proportions of iduronic acid and 4-sulfated galactosaminoglycans were higher. The development of osteoarthrosis-like lesions in the temporomandibular joint of rabbits was studied. Sixteen weeks after the surgical disk perforation, osteoarthrosis-like lesions in both the condylar cartilage and the remaining disk tissue were seen with light microscopy. These lesions were also accompanied by changes in the components of the extracellular matrix. Unlike human arthrotic disks, these tissues showed an elevated content of glycosaminoglycans, evidenced by also an increase in proteoglycans. This increase was mostly confined to large proteoglycans in the disk, while a larger proportion of small proteoglycans than in the respective control tissue was found in the adjacent condylar cartilage. Virtually no aggregability was found in normal or degenerated disk tissue. About 50% of the monomers in the normal condylar cartilage were capable of forming aggregates, while this aggregating proportion decreased slightly in the degenerated tissue. The metabolic mechanism underlying these changes in the proteoglycan content was studied using 35SO4 labeling. In the experimental disk tissue, the population of large proteoglycans had a slightly increased rate of synthesis and a slightly slower degradation rate than in the normal disks whereas the small proteoglycans had higher anabolic and catabolic rates than the controls. However, the amount of newly-synthesized small proteoglycans were unable to compensate for the simultaneous degradation. As a result the proportion of large proteoglycans increased. In the experimental condylar cartilage, all proteoglycans showed similarly increased rates of synthesis. However, here the degradation rate of the two large proteoglycan fractions greatly exceeded that of the synthesis. This resulted in a lowered proportion of these monomers in the experimental tissue, as compared to the control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8503096 TI - Prevalence and technical standard of endodontic treatment in a Swedish population. A longitudinal study. AB - The aims of this thesis were to study longitudinally the tooth mortality, prevalence and technical standard of endodontic treatment as well as the endodontic treatment need in a Swedish population. Furthermore, the prevalences of teeth with crowns and posts were studied as well as the prevalence of apical periodontitis in such teeth, to see if these treatments affected the apical status. Finally, the reasons for and incidence of tooth mortality were investigated to see if the reasons for extractions were correlated to endodontic status, crown or post therapy, respectively. The interobserver variation between the two observers taking part in the investigation was also studied and found to be acceptable. The material consisted of full mouth radiographic surveys from 200 patients examined twice with an interval of 5-7 years. It was found that tooth losses were evenly distributed in the different age-groups and that molars were lost more often than teeth in the frontal region. Furthermore, endodontically treated teeth were lost more often than other teeth and the quality of the root filling affected the risk of tooth losses. Teeth with screw posts were lost more frequently than other teeth, while crowned teeth did not run a higher risk of being lost than teeth without crowns. Caries, including pulpitis and apical periodontitis, was the main reason for tooth extractions. There was a great need for endodontic treatment in the population examined, and the technical standard of the root fillings was poor. A slight improvement in quality of endodontic treatment was evident at the second examination. However, the technical standard was still poor. It is concluded that it is important that dentists in general practice should be better trained in performing endodontic treatment, and that research efforts should be made to find better and simpler methods for endodontic treatment. PMID- 8503097 TI - Oral health in groups of refugees in Sweden. AB - In recent years the impact of ever-increasing numbers of refugees on the resources of the host countries has become a global concern. Health personnel face unanticipated demands complicated by different cultural, ethnic and religious factors and an unfamiliar disease panorama. Sweden today has around 1 million immigrants, 15% of the population. The aim of this thesis was to describe oral status with respect to caries and periodontal conditions, to analyse the need for dental treatment, to evaluate the effect of a preventive dental health programme, to study attitudes and knowledge of preventive dentistry and to describe and analyse utilization of dental services by different groups of adult refugees in Sweden. Three different methods were used: a descriptive clinical survey of a random sample of 193 Chilean and 92 Polish refugees, an experimental survey of a random sample of 159 Chilean refugees and a register survey, using national health statistics, consisting of a random sample of 2,489 refugees arriving in Sweden 1975-1985. The Chilean and Polish refugees had markedly poorer oral status than corresponding Swedish population groups. No association could be found between oral health or estimated treatment need and the length of time in Sweden. The simplified preventive program in the form of group discussion had a lasting effect on improved periodontal conditions and also improved knowledge of dental health care in the group of Chilean refugees. The register survey showed a generally low utilization of dental services but a high dental consumption among adult refugees in Sweden. The total treatment time for a course of treatment showed no marked decrease with subsequent courses of treatment. Immigration may have a profound effect on oral health care needs in a given population by introducing undetermined accumulated needs for oral care, and by stimulating changes in attitudes to and preferences in oral health and care. PMID- 8503098 TI - Tinnitus and craniomandibular disorders--is there a link? AB - Associations between tinnitus and craniomandibular disorders (CMD) were investigated in an epidemiological sample, in tinnitus patients, and in patients attending a 'CMD-clinic'. Natural course of tinnitus was explored in a longitudinal epidemiological study of an elderly population. Several findings indicating a relatively strong relationship between CMD, tinnitus and subjective hearing loss were noted. This relationship seemed to be independent of objectively assessed degree of hearing loss, occupational noise exposure, general morbidity, medication or socioeconomic status. The prevalence of frequent headaches and fatigue or tenderness in jaw muscles was higher in tinnitus patients than would be expected if these conditions were unrelated. About one third of the individuals affected by tinnitus reported influence on tinnitus by jaw movements or pressure on the temporomandibular joint (TMJ). Diurnal bruxism and jaw fatigue appeared to be related to fluctuating tinnitus, vertigo, and hyperacusis. Stomatognathic and biofeedback treatment seemed to be able to reduce or eliminate tinnitus in some patients. Relatively low severity of tinnitus, normal hearing, fluctuating tinnitus, and some signs and symptoms of CMD are believed to constitute predictors of successful treatment outcome. Substantial longitudinal fluctuations with a high occurrence of spontaneous remissions of tinnitus were found in elderly people. PMID- 8503099 TI - Charity care by Texas physicians jumps 47%. PMID- 8503100 TI - TMA updates Hassle Factor Log Form. PMID- 8503101 TI - Hospice case illustrates problems in appealing terminations. PMID- 8503102 TI - Recognizing physicians' rights under exclusive contracts. AB - As hospitals attempt to position themselves as competitive economic units with selected physicians, economic credentialing of hospital medical staff will accelerate. What recourse do physicians on staff have when a hospital enters into an exclusive contract with another group? Do the due process provisions in the medical staff bylaws apply? Is there a right to due process and to a hearing even when no quality issues are involved? This article discusses recent court decisions on this topic, focusing on Texas statutes and case law. PMID- 8503103 TI - Intern program gives teachers "real world" science experience. PMID- 8503104 TI - It's all relative. For many, the medical profession is a family affair. AB - Call up some households and ask, "Is there a doctor in the house?" and you may hear, "Which one do you want?" In a host of Texas families, the medical profession represents a long-standing tradition. Typically, a daughter or son follows in the footsteps of a successful parent. But in some families, the line of physicians goes back several generations and includes many branches of the family tree. A few months back, Texas Medicine invited physicians who come from medical "dynasties" to contact us about their experiences. We received an amazing array of letters, faxes, and phone calls from scores of doctors who have either two or more generations of physicians or several doctor siblings in their families. What they told us about their families was even more fascinating. PMID- 8503105 TI - Clinton's Medicare cuts are only a Band-Aid. PMID- 8503106 TI - Congressional support high for GPCI reforms. PMID- 8503107 TI - The malpractice problem: local action can solve it. PMID- 8503108 TI - Health commissioner praises TMA for stance on public health issues. PMID- 8503109 TI - 'I say condom, you say rubber': communicating sexual topics to adolescent patients. PMID- 8503110 TI - Invisible gas: who's liable? PMID- 8503111 TI - Gamma knife radiosurgery: brain surgery without an incision. AB - Radiosurgery is the precise targeting of ionizing radiation to inactivate or destroy pathologic tissue while sparing adjacent tissue. Like surgery, radiosurgery is done in a single treatment; unlike surgery, radiosurgery does not require an anesthetic or an incision. A specific device for neurosurgery, the gamma knife, uses 201 separate 60Co sources to crossfire gamma rays through a collimator helmet across an intracranial target. This device has been used to treat more than 200 patients at Presbyterian Hospital of Dallas since December 1989. Most patients had either inoperable lesions or residual/recurrent lesions after craniotomy. No patient died and only one developed clinical radionecrosis. Only an overnight hospital stay was required, and patients could resume previous work and activities the day after treatment. Early results parallel reported outcomes in patients treated in Sweden, England, and elsewhere in the United States. In selected patients, the gamma knife is an effective, low-risk, and cost effective alternative to conventional neurosurgery. PMID- 8503112 TI - Musculoskeletal injury: pathologic fractures of the femur. AB - A pathologic fracture is one that occurs in abnormal bone during normal activity or after minimal trauma. Pathologic fractures occur most often in the spine, pelvis, humerus, ribs, and femur. Pain is the primary complaint of patients presenting with pathologic fracture or impending fracture. Pain is also the primary concern for the patient and the major indication for treatment of pathologic femur fractures. PMID- 8503113 TI - Computer article just scratched the surface. PMID- 8503114 TI - Gun control policy need not be all or nothing. PMID- 8503115 TI - Gun control: education is the best control. PMID- 8503116 TI - Family physicians are key to health access problems. PMID- 8503117 TI - Guns don't kill; people do. PMID- 8503118 TI - Dissociation of alpha 2-plasmin-inhibitor-plasmin complex and regeneration of plasmin activity by SDS treatment. AB - In order to understand the mechanism for the complex between alpha 2-plasmin inhibitor (alpha 2-PI) and plasmin to express its specific activity on fibrin autography after SDS-PAGE, we analyzed the effects of SDS on alpha 2-PI molecule and alpha 2-PI-plasmin complex. Treatment of alpha 2-PI by SDS at the concentrations of 0.01% and 0.1% abolished the activity of alpha 2-PI to form a stoichiometric complex with plasmin, whereas it did not interfere with plasmin's activity. More interestingly, in the case of 0.01% SDS, alpha 2-PI was further cleaved to a smaller molecule. Treatment of previously formed alpha 2-PI-plasmin complex by SDS at the concentrations of both 0.01% and 0.1% dissociated the complex and expressed specific amidolytic activity against tripeptide substrate (S-2251), which activity was totally quenched by aprotinin. When alpha 2-PI plasmin complex was treated by higher concentration of SDS for 12 hours, dissociated free plasmin's band could be observed on SDS-PAGE analysis. It is likely, therefore, that the exposure of alpha 2-PI-plasmin complex to SDS during the procedure of SDS-PAGE dissociates the complex and expresses its specific proteolytic activity in fibrin autography. These features of alpha 2-PI and its complex with plasmin are similar to those of plasminogen activator inhibitor type 1 (PAI-1) and its complex with plasminogen activators (PAs), thus they may represent some common features of the SERPINS. PMID- 8503119 TI - Structural characterization of heparin's binding domain for human platelets. AB - The structural features of heparin that are involved in binding to human platelets were investigated by a competitive binding approach. A range of heparin derived glycosaminoglycans (GAGs) with relatively defined structure were prepared by different methods of depolymerization of pharmaceutical heparin, followed by fractionation according to molecular weight and net charge. Competitive binding to platelets was dependent on molecular weight but not on the net charge of the GAGs. The method for depolymerization significantly affected the binding activity of the resulting GAG. Heparinase I and nitrous acid depolymerization produced GAGs with lower binding affinity for platelets than those GAGs derived from the treatment with periodate followed by alkali. The IC20 (concentration producing 20% inhibition of binding) was 0.05 microM for unfractionated heparin, 0.11 microM for a periodate treated GAG, and 2 microM for comparably sized GAGs (M(r) approximately 6,000-8,000) derived by heparinase I or nitrous acid treatment. Thus, the disaccharide units GlcNSO3-6S--IdoA-2S or GlcNSO3--IdoA-2S [(2-deoxy-2 sulfoamido-6-O-sulfo-alpha-D-glycopyranosyl)-(1- 4)-O-(2-O-sulfo-alpha-L idopyranosyluronic acid) or (2-deoxy-2-sulfoamido-alpha-D-glycopyranosyl)-(1-4)-O (2-O-s ulfo-alpha-L-idopyranosyluronic acid)] may be crucial elements for binding to the platelet, because these are known to be preserved during periodate/alkali treatment, but readily decomposed by heparinase I and nitrous acid. Understanding this structural specificity for platelet binding may be useful for the development of heparins with high or low platelet reactivity. PMID- 8503120 TI - Variations of protein C in uremic hemodialysed patients. AB - Protein C has been measured by three different assays (antigenic, amidolytic and chronometric) in 27 end-stage renal insufficient patients before and after hemodialysis. Protein C levels have been compared with other coagulation inhibitors (antithrombin III, protein S) and fibrinolytic parameters. Baseline anticoagulant activity of protein C has been found impaired in eight cases whereas other inhibitors were normal. In four cases, both anticoagulant and antigenic levels were low. In one case, amidolytic method could also found a low activity. Hemodialysis leads to an increase of protein C activity and antigen level. Heparinemia after hemodialysis does not interfere with the chronometric measurement of protein C anticoagulant activity. Total protein level, hematocrit, protein S and antithrombin III are also elevated after hemodialysis. Baseline fibrinolytic parameters are normal and remain unchanged after hemodialysis. The clinical relevance of such modifications is discussed. PMID- 8503121 TI - Inhibition of activated protein C by benzamidine derivatives. AB - In studies on the inhibition of activated protein C (APC) by benzamidine derivatives potent inhibitors of APC were found among anilides of 4-amidinophenyl alpha-aminobutyric acid (Ki = 0.58 mumol/l). Several bis-benzamidine derivatives containing a cycloalkanone linking bridge inhibit APC with Ki values near the micromolar range. Potent and selective inhibitors of thrombin derived from 3- and 4-amidinophenylalanine do not inhibit APC. This is of great importance for further development of these inhibitors as potential anticoagulant drugs. PMID- 8503122 TI - Sodium fluoride induced activation of phospholipase C in intact human platelets does not depend on ADP, PAF or arachidonate products. PMID- 8503123 TI - Revised cDNA sequence of rabbit tissue factor pathway inhibitor. PMID- 8503124 TI - Sneddon's syndrome and antiphospholipid antibodies. PMID- 8503125 TI - [Postoperative analgesia in 3 Dutch hospitals: a pilot study]. AB - Postoperative pain management is an area where preventive measures must be possible. This management will be linked to the expected pain in the postoperative period. To get a better insight in the expectancies and given treatment an inquiry was held in three Dutch hospitals. Of 48 often performed operative procedures in children only in 9 cases agreement was achieved. As a consequence treatment options were divers. Undertreatment is not unlikely. Postoperative pain scores by nurses was in 15 of 48 operative procedures significant higher than those by doctors. PMID- 8503126 TI - [Special forms of analgesia: patient-controlled analgesia]. AB - Patient Controlled Analgesia (PCA) has been used by our Department since 1989 in the management of acute pain following major surgery. A total of 120 patients used the PCA pump in our hospital during the past 3 years. Ages varied from 5 to 20 years with an average of 10.5 years. Duration of administration was 1 day to 14 days with an average of 4 days. The morphine dosages fluctuated from 8 microgram/kg/hr to 37 microgram/kg/hr with an average of 17 microgram/kg/hr. During the first 24 hours postoperatively the average amount of morphine used with the PCAS was 36 microgram/kg/hr, which is higher than the usually prescribed dose of 25 microgram/kg/hr in the fixed rate infusions. No major complications occurred. Pain, sedation and other side effects were assessed by the ward nursing staff. Patient, parent and staff acceptance has been high. We conclude that PCA can be successfully managed by any child who understands the concept of pressing the button when there is pain and we feel that PCA has helped solve many of the problems of providing adequate analgesia in children. It is possible that patients on fixed rate morphine infusions were undermedicated during the first post-operative 24 hours. PMID- 8503127 TI - [Pediatric Pain Groups. Management related to pain in hospitalized children]. AB - By means of multidisciplinary Pediatric Pain Groups in hospitals possibilities are created to implement recent knowledge about prevention of pain and relief of pain in children. The activities of these groups are amongst others: developing and testing pain protocols, applying systematic pain assessment and giving information about pediatric pain. These activities result in a reduction of pain in children and in prevention of needless suffering of pain in hospitalized children. PMID- 8503128 TI - Isolation of zooxanthellatoxins, novel vasoconstrictive substances from the zooxanthella Symbiodinium sp. AB - Isolation of zooxanthellatoxins, novel vasoconstrictive substances from the zooxanthella Symbiodinium sp. Toxicon 31, 371-376, 1993. New polyhydroxypolyenes with potent vasoconstrictive activity, zooxanthellatoxin-A and -B, were isolated from a symbiotic marine alga Symbiodinium sp. These compounds caused sustained contractions of isolated rabbit aorta at concentrations above 7 x 10(-7) M; this effect was abolished in Ca(2+)-free solution or in the presence of verapamil. Both compounds were relatively large molecules (mol. wt about 2900), containing a large number of oxygen atoms and olefinic carbons, thus differing from two other vasoconstrictive marine toxins, palytoxin and maitotoxin, in containing more olefins than palytoxin, and fewer ethereal rings than maitotoxin. PMID- 8503129 TI - Biochemical characterization of a vascular smooth muscle contracting polypeptide purified from Phoneutria nigriventer (armed spider) venom. AB - Biochemical characterization of a vascular smooth muscle contracting polypeptide purified from Phoneutria nigriventer (armed spider) venom. Toxicon 31, 377-384, 1993. Crude Phoneutria nigriventer venom was fractionated by Sephadex, ion exchange and reverse-phase high performance liquid chromatography. One protein (PNV1) with spasmogenic activity in rabbit vascular smooth muscle was isolated and biochemically characterized. PNV1 has 125 amino acid residues and a calculated mol. wt of 13,899. Special features of the amino acid composition of PNV1 are the presence of two disulfide bridges and the high percentage (27%) of Asx and Glx. The N-terminal amino acid sequence indicates that PNV1 is different from other polypeptides isolated from Phoneutria nigriventer venom. PMID- 8503130 TI - Effect of lanthanum ions on the release of acetylcholine induced by tityustoxin, K+ and ouabain from myenteric plexus and brain cortical slices. AB - Exposure of myenteric plexus longitudinal muscles to 2 mM LaCl3 increased the rate of spontaneous [3H]-ACh release. In brain cortical slices La3+ did not affect the spontaneous release of ACh. The release of ACh induced by tityustoxin, ouabain or K+ 50 mM in brain cortex and myenteric longitudinal muscles slices was inhibited by La3+ treatment. It is suggested that tityustoxin, ouabain and K+ release ACh from the same pool that is inhibited by La3+ pretreatment. PMID- 8503131 TI - An enzyme linked immunosorbent assay (ELISA) that discriminates between Bothrops atrox and Lachesis muta muta venoms. AB - As bites by Bothrops atrox and Lachesis muta muta snakes are frequent in the north of Brazil and elicit similar clinical symptoms, an ELISA assay was developed to identify objectively the circulating antigen in the serum of accidentally bitten patients. Antigens common to the two venoms were removed by immunoaffinity techniques and the 'individual component' of each venom used as immunogen to raise rabbit IgGs. Each of these antibodies specifically recognized one venom, and they were used to set up a sandwich-type ELISA. The specificity of the assay was demonstrated by its capacity to identify correctly the circulating antigen in mice experimentally poisoned with either of the two venoms. The ELISA was further used to identify the circulating antigen in the sera of humans bitten by B. atrox or L. muta muta and to follow the kinetics distribution of antigens in experimentally envenomed mice or accidentally bitten patients. The assay is specific, and could therefore be valuable both to clinicians and to epidemiologists. PMID- 8503132 TI - Comparative action of three major ciguatoxins on guinea-pig atria and ilea. AB - The actions of pure ciguatoxin-1, ciguatoxin-2 and ciguatoxin-3 were assessed on the contractile activity of isolated guinea-pig left atria and ilea. Low concentrations of each ciguatoxin caused transient positive inotropy, whereas moderate concentrations induced transient and sustained positive inotropic phases. The transient positive inotropic phase was inhibited by tetrodotoxin or atenolol, indicating this phase stems from indirect effects of the ciguatoxins via the stimulation of intrinsic adrenergic nerves. On atria pretreated with atropine and alpha- and beta-adrenoceptor antagonists to block neural actions of the ciguatoxins, moderate concentrations of each ciguatoxin induced only slowly developing, sustained positive inotropy. ED50s for the indirect positive inotropic phase were 2.7 x 10(-11), 1.6 x 10(-10) and 1.4 x 10(-11) M and for the direct positive inotropic phase were 1.6 x 10(-10), 1.4 x 10(-9) and 1.5 x 10(-9) M for ciguatoxin-1, -2 and -3, respectively, indicating that their effects on neurons are 10-fold (ciguatoxin-1 and -2) to 100-fold (ciguatoxin-3) more potent than those directly on the myocardium. High concentrations of each ciguatoxin additionally induced sustained negative inotropy which could be reversed by lidocaine. On guinea-pig ilea, each ciguatoxin induced a transient contracture which could be abolished by atropine. Each ciguatoxin significantly reduced the contractile response of ilea to nicotine, without affecting the contractile response to acetylcholine. We conclude that ciguatoxin-1, -2 and -3 activate similarly the voltage-dependent Na+ channels in neuronal and myocardial tissues, but vary in their relative affinity for the Na+ channels in these tissues. PMID- 8503133 TI - Proteins isolated from the venom of the common tiger snake (Notechis scutatus scutatus) promote hypotension and hemorrhage. AB - Notechis scutatus scutatus venom contains several toxic acidic proteins called HTa-i which promote hypotension and hemorrhage in mice. They have apparent mol. wts in the 18,000-21,000 range, i.v. LD50 values between 0.5 and 1.5 micrograms/g, and no detectable phospholipase, arginine esterase, proteolytic or hemolytic activities. A polyclonal antibody raised against HTg binds to other purified proteins, suggesting that they are isoforms of the same protein. Many other elapid crude venoms contain proteins which recognize the polyclonal antibody raised against HTg. Crotalid and viperid crude venoms do not recognize this antibody, although some of their component proteins are known to exhibit hypotensive and hemorrhagic activities. A combination of gel-filtration on Sephacryl S-200, cation-exchange and anion-exchange chromatography allows isolation of the N. s. scutatus proteins in high purity. They are the first hypotension-inducing proteins to be purified from an Australian elapid. PMID- 8503134 TI - Differential actions of brevetoxin on phrenic nerve and diaphragm muscle in the rat. AB - The mechanism of inhibition of skeletal muscle function by brevetoxin (PbTX-3) was examined in vitro in the rat phrenic nerve-diaphragm preparation. PbTX-3 in low concentrations (< 0.06 microM) preferentially blocked conduction in the phrenic nerve without altering the resting membrane potential of the muscle fibers. Endplate potential failure occurred in an all-or-none fashion in the presence of PbTX-3 (> 0.06 microM). An increase in the frequency of miniature endplate potentials resulting from nerve terminal depolarization was observed only after endplate potential failure. Higher concentrations of toxin (> 0.3 microM) depressed directly-elicited muscle twitches and produced significant muscle membrane depolarization. Tetrodotoxin was effective in reversing membrane depolarization and alterations in MEPP frequency caused by PbTX-3. These findings suggest that diaphragmatic failure in PbTX-3 is primarily caused by a block of impulse conduction in the phrenic nerve due to a higher sensitivity of nerve than muscle membrane to the toxin. PMID- 8503135 TI - Basic proteinases from Bothrops moojeni (caissaca) venom--I. Isolation and activity of two serine proteinases, MSP 1 and MSP 2, on synthetic substrates and on platelet aggregation. AB - Two serine proteinases, MSP 1 and MSP 2, were isolated from Bothrops moojeni venom by chromatographies on Sephadex G-100, DEAE-Sephacel (pH 7.5) and SP Sephadex C-50 (pH 7.5). Both enzymes are basic glycoproteins. On sodium dodecyl sulfate-polyacrylamide electrophoresis, MSP 1 presented two close protein bands corresponding to the mol. wts of 34,000 and 32,500. MSP 2 behaved as a single chain protein with a mol. wt of 38,000. Specific esterolytic activities of MSP 1 and MSP 2 on alpha-N-tosyl-L-arginine methyl ester (TAME) are 33 mumol min-1 mg-1 and 184 mumol min-1 mg-1, respectively. The most sensitive substrates for the amidolytic activity of both proteinases were the thrombin substrate D-Phe pipecolyl(Pip)-Arg-4-nitroanilide(Nan) and the glandular kallikrein substrate D Val-Leu-Arg-Nan. MSP 1, in a concentration of 10(-8) M, causes platelet aggregation in platelet-rich plasma and washed platelets. It also enhances the ADP-induced platelet aggregation. Prostaglandin E1 (PGE1), phenylmethylsulfonyl fluoride (PMSF) and ethylenediamine tetracetic acid (EDTA) abolished completely the aggregation induced by MSP 1. Torresea cearensis trypsin inhibitor (TCTI) inhibited both amidolytic (Ki = 1.96 x 10(-7) M) and platelet-aggregating (Ki = 1.66 x 10(-7) M) activities of MSP 1. The esterolytic activity of MSP 1 and MSP 2 was completely abolished by PMSF, only partially by soybean trypsin inhibitor (SBTI) and benzamidine and not affected by Trasylol. MSP 2 was also inhibited by TCTI (Ki = 0.7 x 10(-7) M). PMID- 8503137 TI - Bibliography of toxinology. PMID- 8503136 TI - Basic proteinases from Bothrops moojeni (caissaca) venom--II. Isolation of the metalloproteinase MPB. Comparison of the proteolytic activity on natural substrates by MPB, MSP 1 and MSP 2. AB - A basic metalloproteinase active on casein was isolated from Bothrops moojeni venom by chromatography on Sephadex G-100, DEAE-Sephacel, SP-Sephadex C-50 and Sepharose 12. The enzyme, named MPB, is not hemorrhagic and presents only traces of blood-clotting activity. On polyacrylamide gel electrophoresis at pH 4.3, MPB presented a single and diffuse protein band. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the enzyme presented two protein bands corresponding to mol. wts of 65,000 and 55,000, which stained with Schiff's reagent. The proteolytic activity of MPB was inhibited by ethylenediaminetetracetate, 1,10-phenanthroline and dithiothreitol. The proteolytic activity of MPB and the serine proteinases MSP 1 and MSP 2 on natural substrates indicates differences in hydrolytic specificity among these enzymes. All fibrinogen chains were degraded by the three proteinases, but MPB is the most active. On fibrin, the proteinases hydrolyzed only the alpha-chain and alpha polymer, leaving the beta-chain and gamma-dimer apparently untouched. The native type I collagen was partially hydrolyzed by the three enzymes but no digestion product was detected. On the contrary, calf and guinea-pig skin type I gelatins were readily digested by MSP 1 and MSP 2 producing different hydrolysis patterns. MPB was the least active proteinase on the gelatins. The digestion of fibronectin showed an inversion in the specificity of these proteinases. MPB was the most active on fibronectin, while MSP 1 and MSP 2 promoted a faint, partial hydrolysis on this protein. PMID- 8503138 TI - Steady-state plasma concentrations of mianserin and its major active metabolite, desmethylmianserin. AB - The steady-state plasma concentrations of mianserin and its major active metabolite, desmethylmianserin, were measured in 76 depressed patients receiving 30 mg of mianserin at bedtime. There were considerable inter-individual variations in the steady-state plasma concentrations of these compounds; the plasma concentrations of mianserin plus desmethylmianserin were within the therapeutic range suggested previously by us in only 43% of the patients. With advancing age, the plasma concentrations of mianserin increased significantly, while those of mianserin plus desmethylmianserin remained unchanged. Sex, smoking, and coadministration of benzodiazepines did not affect the drug's metabolism. There was no evidence that the kinetics of these compounds were nonlinear with increasing doses. The present study thus suggests that measuring the plasma concentrations of mianserin and desmethylmianserin contributes to rational treatment with this drug, that age, sex, smoking, and coadministration of benzodiazepines are not important factors in determining the dose, and that these compounds have linear kinetics. PMID- 8503139 TI - Prediction of plasma concentrations of mianserin and desmethylmianserin at steady state from those after an initial dose of mianserin. AB - The relationships between the plasma concentrations of mianserin and desmethylmianserin at 18 h after initial dosing and those at steady state were studied in 19 depressed patients receiving 30 mg of mianserin at bedtime. Significant linear relationships were observed for mianserin, desmethylmianserin, and mianserin plus desmethylmianserin. The present study thus suggests that the plasma concentrations of these compounds after an initial dose of mianserin can be used for the prediction of an optimal dose. PMID- 8503140 TI - High-performance liquid chromatography of clomipramine and metabolites in human plasma and urine. AB - An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the tricyclic antidepressant clomipramine and six metabolites: desmethylclomipramine, 2- and 8-hydroxy-clomipramine, 2- and 8 hydroxydesmethylclomipramine and didesmethyl-clomipramine in plasma and urine. In addition, clomipramine N-oxide was determined in the unconjugated fraction of urine. The method is based on a three-step liquid-liquid extraction, the chromatographic eluent was 30% acetonitrile and 70% aqueous sodium perchlorate solution, pH 2.5, and the UV detection was performed at 220 nm. The method was applied to the analysis of samples followed by oral doses of clomipramine to patients and healthy volunteers. PMID- 8503141 TI - Demonstrating instrument-reagent flexibility: a carbamazepine enzyme immunoassay reagent system. AB - Versatility of immunoassay reagents is beneficial to laboratories seeking cost effective combinations of tests and automated instrumentation. In such cases, both immunoassay analytical performance and instrument independence must be assessed. Considering this, we determined the compatibility of a new carbamazepine EMIT 2000 reagent system with two fully automated but different kinetic rate analyzers (Hitachi 704 and Cobas MIRA), comparing results to a reagent-dedicated fluorescent polarization automated device (TDx) as reference. In order to more stringently assess reagent antibody specificity, we tested recovery of purified carbamazepine spiked into sera pooled from different hospital groups (normal, renal failure, hepatic failure, term pregnancy, cord blood). Cross-reactivity was additionally tested using patient sera containing various amounts of tricyclic antidepressants, compounds structurally but not functionally related to carbamazepine. Despite distinct operational differences between analyzers, precision (< 5.5% CV) and accuracy (> 95% recovery) compared well to the TDx method. However, when carbamazepine was spiked into sera from patients with hepatic failure or at term pregnancy, all three methods measured a negative bias in recovery of 16-20%. No significant cross-reactivity was observed at normal therapeutic concentration of certain tricyclic compounds, though measurable cross-reactivity was detected when present at toxic serum concentrations. We conclude that the EMIT carbamazepine immunoassay is adaptable to the different kinetic rate analyzers studied. Analytical specificity should, furthermore, be assessed in the context of interferences likely to be clinically encountered. PMID- 8503142 TI - Lithium population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. AB - Routine clinical pharmacokinetic data (n = 303) collected from 90 patients receiving lithium have been analyzed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analyzed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of lithium was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicated that lithium clearance was influenced by the demographic variables of age, total body weight, and serum creatinine. The interindividual variability in lithium clearance was modeled with proportional error with an estimated coefficient of variation of 25.1%. The intraindividual variability, or residual error, was 14.3%. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the minimum steady-state lithium concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring. PMID- 8503143 TI - Five years of anticonvulsant monitoring on site at the epilepsy clinic. AB - The influence of antiepileptic drug monitoring on site at the epilepsy clinic was assessed in a prospective way by recording physicians' decisions before and after the drug concentration became available over the five-year period including 1986 to 1990. A total of 2,857 assays (1,121 carbamazepine, 798 phenytoin, 622 sodium valproate, and 72 phenobarbital) were performed during 2,696 hospital attendances on 618 epileptic patients. A gradual reduction in the proportion of visits monitored annually was observed (1986: 42%; 1987: 51%; 1988: 44%; 1989: 39%; 1990: 28%; p < 0.01). In 481 (17.8%) visits a change in management resulted from knowledge of the drug concentration. This was not an automatic response, as a large minority of unexpected results did not produce such an alteration. The proportion of decisions to adjust the drug dose after an unexpected result, however, tended to increase over the years of the study (1986: 43%; 1987: 70%; 1988: 60%; 1989: 78%; 1990: 54%; p < 0.01). Changes in anticonvulsant dose following an unexpected result were observed in "low" (59%), "therapeutic" (61%), and "high" (52%) concentration categories. Possible benefit for patients can be inferred from the observation that more assay results fell within the target range in the last (61%) compared with the first (33%) year of monitoring (p < 0.01). PMID- 8503144 TI - Postmortem concentrations of phenobarbital, carbamazepine, and its metabolite carbamazepine-10,11-epoxide in different regions of the brain and in the serum: analysis of autoptic specimens from 51 epileptic patients. AB - Postmortem concentrations of phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex, and white matter, as well as cerebellum) of 51 deceased epileptic patients. The concentrations of PB and CBZ in the frontal cortex were approximately 1.4 times higher, and of CE were 1.1 times higher than the total concentrations in the serum. Furthermore, the concentrations of PB in the frontal cortex were approximately 2.1 times, of CBZ were 4.5 times, and of CE were 2.1 times higher than the free concentrations in the serum. The distribution of the three substances in the brain is rather homogeneous and seems to follow basic physicochemical principles. This means that the concentrations of the substances in the white matter are, depending on their lipophilicity, modestly but significantly higher than in the cortex. Small and in part statistically significant concentration differences between different regions of the cortex and also of the white matter may be explained by differences in the lipid content of the respective regions and by the lipophilicity of the respective substance. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical to those in the frontal cortex. Remarkably increased or decreased concentrations were not observed in any region of the brain. PMID- 8503145 TI - Analysis of nicotine content of hair for assessing individual cigarette-smoking behavior. AB - The concentration of nicotine in hair was measured by a capillary gas chromatograph with a nitrogen-phosphorus detector after hair was dissolved in 2.5 N sodium hydroxide and nicotine was extracted using diethyl ether. In hair samples obtained from 36 smokers, who had smoked > or = 3 years, there was a significant positive correlation between the concentration of nicotine and the number of cigarettes consumed daily (r = 0.685; p < 0.001). The nicotine content of white hair was much less than that of black hair collected from the same subjects with grizzled hair. The above findings were confirmed by an animal experiment, in which nicotine (0.2, 0.6, and 2 mg/kg/day for 2 weeks) was administered intraperitoneally to pigmented rats whose hair had been removed beforehand by plucking from an area of the back of each rat. The hair which grew back in the denuded area was plucked and collected one week after the last administration of nicotine. The nicotine concentration in the brown hair of the back correlated with the given dose (r = 0.824; p < 0.001). In a separate experiment, hairs were removed from areas of back and thorax, and nicotine delivered to the rats for 4 weeks by an osmotic pump implanted under the skin, showing that the concentration in the whitish hair was much lower than that in brown hair. Finally, hair samples were collected from 14 subjects who had participated in a smoking cessation program over 6 months and who abstained from cigarette smoking. The axial distribution of nicotine along the hair shafts was determined for each subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503146 TI - Citrate and urease-induced crystallization in synthetic and human urine. AB - The effects of citrate on the different phases of urease-induced crystallization were studied using Coulter counter techniques and optical microscopy. Citrate increased urine pH and markedly delayed the initiation of the crystallization (nucleation) in both human and synthetic urine. In synthetic urine, particle aggregation and especially particle growth were delayed and inhibited by citrate. In human urine, aggregation was distinctly inhibited by citrate. It appears that the susceptibility of urine to form crystals in the presence of urease activity is influenced by its citrate concentration. PMID- 8503147 TI - Beta-D-glucan concentrations detected by Toxicolor and Endospecy tests in the urine of patients with urinary fungal infections. AB - Beta-D-glucan is an essential component of the cell wall of fungi. We measured its concentration in the urine of patients with funguria using the chromogenic endotoxin assay kits, Toxicolor and Endospecy. These assay systems use the same Limulus coagulation enzymes. Since the Endospecy test detects endotoxin but not factor G, which is activated by beta-D-glucan, the beta-D-glucan concentration can be calculated by subtracting the Endospecy value from the Toxicolor value. Concentrations of beta-D-glucan were found to be significantly higher in urine samples from patients with funguria (> or = 10(3) colony-forming units/ml) than in non-infected samples. PMID- 8503148 TI - Proportions of fiber types in the external urethral sphincter of young nulliparous and old multiparous rabbits. AB - The proportions of fast and slow myosin molecules in specimen's of the external urethral sphincter (EUS) from 6 young nulliparous (6-month-old) and 6 old multiparous (2-year-old) rabbits were studied using myosin heavy chain electrophoresis. The percentages of fast and slow myosin molecules were 80.4 +/- 4.5% and 19.6 +/- 4.5% in the EUS from nulliparas, and 68.7 +/- 6.3% and 31.3 +/- 6.3% in the EUS from multiparas. The difference between the two groups was significant (P < 0.01). We suggest that a selective decrease in the volume of type 2 (fast) muscle fibers and/or conversion of type 2 to type 1 (slow) muscle fibers had taken place in the EUS of old multiparas. The proportional change in the constituent muscle fibers of the EUS with aging may play a role in human genuine stress incontinence. PMID- 8503149 TI - Optimization of uretero-intestinal anastomosis in urinary diversion: an experimental study in dogs. I. Evaluation of the Le Duc technique. AB - Experimental evaluation of uretero-ileal reimplantation was carried out in 10 adult mongrel dogs. One half of the ureters (10) were implanted into ileal reservoirs using the classic Le Duc technique. In the other half, the implanted ureters were covered by ileal mucous membrane. Following the classic Le Duc technique, 40% of the reimplanted ureters showed evidence of either reflux and/or stenosis resulting from shortening and fibrosis of the tunnel. The remaining 60% were perfect due to spontaneous nipple formation at the implantation sites rather than to creeping of the intestinal mucosa. In contrast, none of the ureters examined was either refluxing or stenotic. This study outlines the critical importance of covering the implanted ureters with mucosa to avoid the ureteric adventitia being exposed to the irritative effects of urine with subsequent scarring. PMID- 8503150 TI - Optimization of uretero-intestinal anastomosis in urinary diversion: an experimental study in dogs. II. Influence of exposure to urine on the healing of the ureter and ileum. AB - The influence of exposure to urine on the ureteric adventitia and the ileal mucous membrane was studied in 10 mongrel dogs. When the ureter was implanted freely into the lumen of the bladder its adventitia became the seat of granulation tissue formation. This is later covered by creeping of transitional epithelium lining the ureter, forming what is in effect a ureteral nipple. Final healing is associated with an unpredictable amount of scarring. Furthermore, it was noted that healing and creeping of the ileal mucous membrane are impeded in the presence of urine. The sum of these effects is that ureters implanted in an open sulcus of the small intestine are not covered by intestinal epithelium, they tend to form spontaneous nipples and their healing is associated with either stenosis or reflux in some 30% of cases. PMID- 8503151 TI - Optimization of uretero-intestinal anastomosis in urinary diversion: an experimental study in dogs. III. A new antireflux technique for uretero-ileal anastomosis: a serous-lined extramural tunnel. AB - A new antireflux uretero-ileal reimplantation technique suitable for use with bladder substitutes is presented. This procedure entails creation of a serous lined extramural tunnel. Following detubularization of the bowel segment, the adjacent flaps are approximated by continuous 4/0 non-absorbable sutures 1.5 cm from the cut edges. The ureters are laid in the trough thus fashioned. "Button holes" are created in the bowel flaps and a mucosa-to-mucosa uretero-ileal anastomosis is carried out. The mucosal edges of the flaps are then approximated by one layer of continuous 4/0 (PGA) suture resulting in closure of this artificial tunnel. The feasibility and functional outcome of this technique were experimentally investigated in 8 dogs. Follow-up was carried out up to 30 weeks. Assessment by intravenous urography and ascending studies showed that the procedure is an efficient method of providing an unobstructed unidirectional flow of urine. PMID- 8503152 TI - Comparative study of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tritiated thymidine in a chemosensitivity test using collagen gel matrix. AB - An organ culture system using collagen gel matrix (CGM) was modified and established successfully as a rapid and convenient method for determination of anti-cancer drug sensitivities. The cell viability of a tumor fragment was measured by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to a colored formazan product, which allowed for quantitative and simple analysis. The sensitivities of KK-47 bladder tumor from nude mice to various anti-cancer drugs tested corresponded closely to those determined in the original CGM assay system using tritiated thymidine, which has a high clinical correlation. Our modified method can be used as a practical and highly reproducible chemosensitivity test in vitro. PMID- 8503154 TI - Experimental technique simulating oxalocalcic renal stone generation. AB - A new technique simulating some of the conditions experienced by papillar and caliceal oxalocalcic stones during the early stages of their generation was developed. This technique enables the study of how conditions prevailing at calculogenesis, such as pH, composition of urine and presence of admixtures, influence the rate of formation and development, the crystalline texture and the composition of the concretion formed. Results achieved with this technique demonstrate that: (1) an appropriate substrate always gives rise to a crystalline concretion if it is in contact with supersaturated urine; (2) primary agglomeration plays a significant role in concretion development whereas secondary agglomeration is of minor importance; and (3) citrate and pyrophosphate exert a considerable influence on the shape and composition of particles constituting the concretion. PMID- 8503153 TI - Application of polymerase chain reaction-single strand conformation polymorphism analysis to the diagnosis and screening of adenine phosphoribosyltransferase deficiency. AB - Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method used to identify point mutations in a given sequence of genomic DNA. We applied this method to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes were amplified and labeled simultaneously with [alpha-32P]dCTP (cytidine triphosphate) by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes-APRT*QO and APRT*J-gave bands clearly distinct from those of the equivalent normal APRT genes. Using this method we diagnosed both homozygotes and heterozygotes for defective APRT genes. On screening 80 Japanese individuals for polymorphism or mutations by PCR-SSCP we did not find any alterations leading to a false positive diagnosis. These findings suggest that PCR-SSCP, in addition to being rapid and sensitive, is a useful diagnostic method which is highly specific in detecting mutant APRT genes in the Japanese population. PMID- 8503155 TI - Perspectives on gastrointestinal endoscopy. AB - A historical perspective on the development of veterinary endoscopy is given. The current endoscopic requirements and indications are discussed. The diagnostic and therapeutic capabilities of gastrointestinal endoscopy are reviewed. Speculation on the diagnostic capabilities for the future in small animal gastrointestinal endoscopy is given. PMID- 8503156 TI - Antiulcer therapy. AB - Perhaps older drugs to treat ulcers, such as antacids, are just as effective as the newer drugs, but veterinarians have all but abandoned these drugs in favor of H2-receptor antagonists, sucralfate, and omeprazole. For most patients, one of the H2-receptor antagonists or sucralfate is probably the initial drug of choice. For patients refractory to these drugs or for which once-a-day dosing is desirable, omeprazole has an advantage. The doses for these drugs are listed in Table 1. Patients presented with acute bleeding ulcers should be managed with emergency therapy. Fluid therapy and blood transfusions are the essential elements of the initial therapy. Surgical resection of the ulcers may be necessary, and most patients should be administered H2-receptor antagonists or sucralfate while they recuperate. Longer term therapy with antiulcer drugs will depend on the predisposing factors that initiated the ulcers. The practice of lavage of the stomach with iced saline or epinephrine to stop bleeding from gastric ulcers is not effective. A common cause of ulcers in small animals is the administration of NSAIDs. Ulcers caused by these agents should be managed like any other ulcers. Fortunately, if ulcers are diagnosed early, they usually heal once the NSAID is discontinued. Unfortunately, many NSAID-induced ulcers identified postmortem did not produce clinical signs, and the ulcers may not be apparent until severe bleeding occurs. In cases in which patients are at risk for developing ulcers from NSAIDs, there may be an advantage in administering the synthetic prostaglandin misoprostol. In many patients that are sensitive to the GI irritation of NSAIDs, switching from one NSAID to another may alleviate some of the signs. Buffered aspirin may be somewhat less irritating than plain uncoated aspirin but will not completely prevent ulcers. The administration of enteric-coated aspirin tablets to dogs is discouraged, because systemic absorption from these tablets is unpredictable. PMID- 8503157 TI - Gastric dilatation volvulus. Surgical prevention. AB - Definitive surgical management of gastric dilatation volvulus involves gastric repositioning, gastric resection when indicated and surgical formation of a permanent adhesion to prevent recurrence of the problem. Derotation and gastropexy procedures are recommended as soon as the patient is a reasonable anesthetic risk. Splenectomy and pyloric outlet procedures are of questionable value in preventing recurrence in the majority of cases. In North America, most veterinary surgeons perform right-sided antral gastropexy as a means of preventing recurrence. The technical advantages and disadvantages and experimental and clinical results of several techniques, including the tube gastrostomy, incisional gastropexy, circumcostal gastropexy, and belt-loop gastropexy, are discussed. PMID- 8503158 TI - Percutaneous endoscopic gastrostomy. AB - Over the past 5 to 7 years, the veterinary profession has benefitted from our increased ability to provide nutrition to the small animal patient who cannot or will not eat. The adaptation of the percutaneous endoscopic gastrostomy (PEG) for use in the dog and cat deserves a great deal of credit in advancing the level of care we can now give to the chronically ill or critical care patient. The PEG is a relatively simple technique that has proved to be a very cost-efficient way to maintain the nutritional status of the small animal patient. In the author's experience, owner acceptance of using the PEG in the home environment on a chronic basis has been excellent. PMID- 8503159 TI - Acquired antral pyloric hypertrophy in the dog. AB - Acquired antral pyloric hypertrophy is one of the most common causes of pyloric obstruction in the small (10 kg) mature or old dog. Clinical signs include chronic intermittent vomiting after meals and occasional weight loss or abdominal distension. Definitive diagnosis is made by exploratory laparotomy and histologic examination of excised tissues. Most dogs with acquired antral pyloric hypertrophy become clinically normal after surgical correction of the gastric outlet obstruction. PMID- 8503160 TI - Feline inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is one of the most common causes of chronic vomiting and diarrhea in cats. A definitive diagnosis is made only by biopsy. This article presents an overview of differential diagnosis of IBD in cats. Treatment of this syndrome is reviewed in detail. A great majority of cats with IBD can be managed successfully. This can be best assured by establishing a definitive diagnosis relatively early in the course of the disease. PMID- 8503161 TI - Megacolon in cats. The role of colectomy. AB - In cats, clinical signs of constipation usually respond to laxatives, fecal softeners, enemas, and dietary management. Uncommonly, constipation is chronic and is associated with a marked increase in the diameter of the colon. When megacolon is present, constipation responds poorly to medical therapy. Without surgical treatment, megacolon may become an intolerable problem, with euthanasia of the cat as the probable outcome. Subtotal colectomy is now established as a satisfactory treatment for idiopathic megacolon in cats. Recently, removal of the colon has been used successfully to treat chronic constipation and megacolon associated with mechanical obstruction of the pelvic canal caused by stenosis from malunion of pelvic fractures. Colectomy has minimal long-term effects on enteric function in cats. PMID- 8503162 TI - Exocrine pancreatic insufficiency. AB - EPI in dogs represents a well-defined condition that can now be diagnosed simply by the analysis of a single serum sample for TLI. A low TLI concentration represents a highly sensitive and specific test for EPI and may also predict the development of disease before the onset of clinical signs. A lack of pancreatic enzymes results in interference with degradation of the major dietary constituents, and there are secondary changes in the small intestine including a decreased synthesis of enterocyte proteins; bacterial overgrowth in the proximal intestine (SIBO); and malabsorption of vitamins, including cobalamin. Management with uncoated pancreatic extract and a low-fat, high-quality protein diet fed in small, divided meals should be effective in most cases. In animals showing a poor response, additional treatment may be necessary with long-term oral antibiotic for SIBO and H2-receptor blockers before a meal to inhibit acid secretion and minimize degradation of pancreatic extract. Diagnosis of the relatively rare cases of EPI in cats is best achieved by analysis of fecal trypsin by the use of specific substrates until a TLI test becomes readily available, and management should follow similar principles to those established for dogs. The major question for the future is the underlying cause of pancreatic acinar atrophy in dogs, particularly the relative importance of genetic and environmental factors. This information may allow detection and elimination of a genetic abnormality by selective breeding or prophylactic treatment that would prevent the development of the disease. PMID- 8503163 TI - Congenital portosystemic shunts in the dog and cat. AB - Congenital portosystemic shunts were not reported as a clinical entity until the 1970s. Historical and clinical findings and surgical data were detailed in the 1980s. The methods of surgical management learned in the last decade offer challenges of redefinition to surgical management in the 1990s. PMID- 8503164 TI - Serum bile acids in companion animal medicine. AB - Quantification of total serum bile acids is used as a method for appraising liver function and perfusion in contemporary small animal practice. This article provides a historical perspective and a comprehensive review of bile acid physiology, laboratory methodologies for bile acid quantification, and normal values published for total serum bile acids measured using the spectrophotometric enzymatic method and for serum bile acids measured using validated radioimmunoassay procedures. The variables influencing the enterohepatic circulation of bile acids and, consequently, the fasting and postprandial serum bile acid concentrations are discussed with the intent of clarifying the application of test results to clinical patients. A brief discussion of the therapeutic use of dehydrocholate and ursodeoxycholic acid in clinical patients is provided. PMID- 8503165 TI - Hepatotoxicity associated with pharmacologic agents in dogs and cats. AB - Historical aspects, mechanisms, and treatment of hepatotoxicity associated with pharmacologic agents in dogs and cats are discussed. All agents that cause clinically relevant drug-induced hepatotoxicity have been reviewed within the last 5 years; therefore, only selected drugs that more recently have been observed to cause hepatic injury in companion animals are described in detail. These include diethylcarbamazine/oxibendazole, phenobarbital, and trimethoprim/sulfadiazine. PMID- 8503166 TI - Developments in the treatment of gastrointestinal parasites of small animals. AB - The use of anthelmintics introduced over the past 25 years is discussed. The spectrum of action, efficacy, and toxicity of benzimidazoles, ivermectin, milbemycin, praziquantel, and epsiprantel are considered. PMID- 8503167 TI - Homologous superinfection of both producer and nonproducer HIV-infected cells is blocked at a late retrotranscription step. AB - An HUT-78 cell clone (F12) chronically infected by a nonproducer HIV-1 variant (Federico et al., (1989) AIDS Res. Hum. Retroviruses 5, 385-396) is fully resistant to superinfection with HIV-1 or HIV-2. We demonstrate that, in spite of the down-regulation of CD4 receptors, superinfecting-HIV-1 and -HIV-2 cross the F12 plasma membrane (even in the presence of OKT4A monoclonal antibodies) but fail to complete retrotranscription. We utilized a series of polymerase chain reaction primers designed to detect certain steps in the reverse transcription process. Superinfecting-HIV-1 (an African strain) and -HIV-2 are detectable using primers specific for env (for HIV-1), 5' LTR (the R and U5 regions), and vpx (for HIV-2). No amplification is visible when primers amplifying either HIV-2 gag or the "primer binding site" region of 5' LTR of HIV-2 are used. DNA-PCR performed on DNAse-pretreated HIV-1 and HIV-2 stocks failed to show any amplification. This rules out that any extra- or intravirion viral DNA contamination may have interfered with our results. In addition, no DNA amplification was observed in F12 and HUT-78 cells exposed to heat-inactivated HIV-2. Finally, when the nonproducer F12 cells as well as control CEMss cells are transfected with the HIV 1 infectious molecular clone pNL4-3, progeny infectious virus is obtained. These findings indicate that reverse transcription of HIVs superinfecting F12 cells is prevented from completing viral DNA synthesis. A similar block occurs in HIV-1 infected producer cells. When integration of the HIV genome into the F12 genome is achieved via transfection of a molecular clone, the virus life cycle can proceed as in control CEMss cells. PMID- 8503168 TI - Hemagglutination properties and nucleotide sequence analysis of the fiber gene of adenovirus genome types 11p and 11a. AB - The fiber has been suggested to serve as the ligand between the adenovirus capsid and the host cell receptor. The two genome types, Ad11p and Ad11a, of adenovirus serotype 11 display different tropisms. The fiber amino acid sequences of the two genome types have been deduced from the 975 nucleotides that encoded a fiber polypeptide of 35,500 Da. The fiber consists of a tail, a shaft, and a knob region. The amino acids 44 to 140 form a typical shaft domain of six 15-residue repetitive motifs. Ten amino acids in the Ad11p fiber shaft were substituted in Ad11a. Five unpolar residues have been replaced by four polar and one unpolar amino acid. In the knob region, a total of 14 amino acid mismatches were noted between Ad11p and Ad11a. The amino acid sequence Asn-Asp-Glu at positions 283 to 285 in Ad11p was changed to Arg-Ala-Asp in Ad11a. The sequence Thr-Leu-Trp-Thr from positions 133 to 136 was conserved in all analyzed human and canine adenoviruses. The polypeptide at positions 235 to 244, Phe-Met-Pro-Ser-Thr-Thr Ala-Tyr-Pro-Phe, probably contains a subgenus epitope, since it is conserved among subgenus B adenoviruses. Ad11p aggregated rhesus and vervet erythrocytes at 37 degrees, 22 degrees, and at 4 degrees, respectively, whereas Ad11a did not display hemagglutination under the same conditions. The complete fibers of Ad11p and Ad11a share an overall amino acid homology of 92.3%. The homology within the shaft and the knob region was 89.7 and 92.4%, respectively. These variable amino acids should be expected to be responsible for the differences in hemagglutination and tropism examplified by the persistent urinary tract infections caused by Ad11p and the acute respiratory tract infections caused by Ad11a. PMID- 8503169 TI - Protein folding studies in vivo with a bacteriophage T4 expression-packaging processing vector that delivers encapsidated fusion proteins into bacteria. AB - A cloned phage T4 gene which expresses the nonessential capsid scaffold protein IPIII was modified to permit construction and packaging of protein fusions within the capsid. IPIII deletion phage packaged IPIII-beta-galactosidase, IPIII-beta globin, and IPIII-beta-globin-beta-galactosidase fusion proteins; the latter protein fusion was specifically processed by the T4 gene 21 head morphogenetic proteinase in vivo at a consensus leu(ile)-P1-glu* cleavage site to regenerate beta-galactosidase. Phage inject IPIII-beta-galactosidase protein into bacteria, but less activity is recovered in infections of Escherichia coli dnaK or groEL mutants, suggesting that these host molecular chaperones are required for beta galactosidase intracellular folding. This expression-packaging-processing (EPP) vector directs protein fusions into capsids for easy detection and purification and permits study of protein delivery and folding in bacteria. PMID- 8503170 TI - Structure, sequence, and function correlations among parvoviruses. AB - The capsid protein sequences of 10 representative parvoviruses were aligned against the sequence and three-dimensional structure of canine parvovirus (CPV). The structure of CPV was then analyzed after mapping onto it position-dependent sequence similarity scores and the locations of residues that are phenotypically important in other parvoviruses. Antigenicity is primarily associated with external exposed loops of high sequence variability. Amino acids in the canyon, a surface depression encircling each fivefold axis, are well conserved, but may have a function other than external receptor binding. Residues important to parvoviral cell specificity and erythrocyte binding are scattered near the rim of a less-conserved depression near the twofold axis, and on a shoulder of the threefold spike. The number of residues involved in various interactions and their conservation and properties suggest that uncoating may involve separation of fivefold and twofold related subunits before those related by threefold symmetry. The inner surface residues of the capsid are generally more highly conserved than those on the outer surface, presumably due to interactions with DNA, although the binding site that contains ordered DNA in the structure is not especially conserved. PMID- 8503171 TI - Mutational analysis of conserved tyrosines in the NS-1 protein of the parvovirus minute virus of mice. AB - The NS-1 gene of the parvovirus minute virus of mice encodes a multifunctional protein essential for viral DNA replication and gene expression. In addition to possessing DNA helicase and ATPase activities, NS-1 forms a covalent linkage with the 5' ends of viral DNA and is a strong candidate for the site-specific nicking closing enzyme postulated to be involved in the resolution of concatemers and terminal hairpin structures that arise during parvoviral DNA replication. Since the covalent linkage between NS-1 and the 5' terminus of MVM DNA resists alkali and mild acid treatment, a tyrosine phosphodiester is likely to be involved. To map domains responsible for this activity, mutations converting tyrosine to phenylalanine were introduced into the NS-1 gene using oligonucleotide-directed mutagenesis and their effect on the DNA replication and transcriptional activation functions of NS-1 was examined in transient in vivo transfection assays. Replacement of Tyr-188, Tyr-197, Tyr-210, Tyr-310, Tyr-422, or Tyr-550 with phenylalanine greatly reduced the ability of NS-1 to complement the replication of the target genome ins 20B in COS-7 cells. However, a Ser-545 to Thr-545 substitution in the Phe-550 mutant restored DNA replication activity. Replacement of 5 other tyrosines in NS-1 with phenylalanine either enhanced (Phe 6), had a moderate inhibitory effect (Phe-209) or had no effect (Phe-47, Phe 227 and Phe-543) on its DNA replication activity. Two of the 11 phenylalanine substitution mutations, Phe-188 and Phe-197, also greatly reduced the ability of NS-1 to transactivate the p38 promoter and displayed a dominant negative phenotype with respect to transactivation. Since the remaining tyrosines in MVM NS-1, Tyr-152, Tyr-252, Tyr-374, and Tyr-595, are not conserved among the NS-1 proteins encoded by porcine and feline parvoviruses, they are presumed to be nonessential for the normal functioning of NS-1. The results point to a role for either Tyr-188, Tyr-197, Tyr-210, Tyr-310, or Tyr-422 in forming a covalent linkage with viral DNA and further suggest a regulatory role for several tyrosines in other DNA replication and transcriptional activation functions of NS 1. PMID- 8503172 TI - Assembly of the matrix protein of simian immunodeficiency virus into virus-like particles. AB - To obtain a better understanding of the processes of assembly and morphogenesis of simian immunodeficiency virus (SIV), recombinant vaccinia viruses containing regions of the gag-pol open reading frame were constructed and their intracellular expression as well as the ability of the Gag polypeptides to be released into the culture medium as constituents of virus-like particles were studied. Biochemical and electron microscopy analyses of cells infected with a recombinant expressing only the SIV matrix (MA) domain of the Gag polyprotein (v p17 gag) showed that this protein self-assembles into 100-nm virus-like particles which are released into the culture medium. Interestingly, coexpression of SIV MA and Env proteins resulted in incorporation of gp120 and gp41 proteins into the recombinant p17-made particles. In addition when a positively charged domain of SIV MA (residues 26-33), which is highly conserved among all HIV and SIV MA proteins, was mutated into an acidic region, particle release was abolished without affecting protein expression, processing, or stability. Further characterization of the phenotype of this mutant by electron microscopy indicated that this mutant was blocked at the stage of assembly. These results suggest that SIV MA protein, along with its function in myristic acid-mediated membrane targeting, has intrinsic information for self-assembly as well as incorporation of viral Env glycoproteins into particles. PMID- 8503173 TI - Dissociation of the lipid-containing bacteriophage PRD1: effects of heat, pH, and sodium dodecyl sulfate. AB - The double-stranded DNA bacteriophage PRD1 replicates in Escherichia coli and Salmonella typhimurium. It has an outer protein coat surrounding a membrane. The phage lipids are derived from the host, but the membrane proteins are of phage origin. In this investigation we studied the effects of heat, pH, and sodium dodecyl sulfate on the integrity of phage particles. Heat and high pH result in the release of the main coat protein, P3, as trimers, whereas treatment of phage particles with detergent results in the solubilization of the membrane. Our results enable a distinction to be made between the phage structural proteins that are embedded in the lipid bilayer and those that appear to be more loosely associated with the membrane. PMID- 8503174 TI - Isolation of a phospholipid-free protein shell of bacteriophage PRD1, an Escherichia coli virus with an internal membrane. AB - PRD1 is a double-stranded DNA virus infecting Escherichia coli and Salmonella typhimurium. It has an icosahedral outer protein capsid which encloses the viral membrane, inside of which resides the phage genome. In this investigation we demonstrate the detergent resistance of the intact virus particles. The membrane of empty DNA-free particles, however, is very sensitive to detergent action. We assume that their sensitivity is due to the access of detergents through a portal structure to the virus interior. Using the anionic detergent sodium dodecyl sulfate, it is possible to obtain a shell structure composed of the major coat protein P3 alone. The treatment of empty particles with the milder nonionic detergents n-octyl beta-D-glucopyranoside and Triton X-100 yielded P3 particles which retained the membrane-associated proteins P7 and P11. Deoxycholic acid treatment yielded shells of intermediate composition between those obtained with the nonionic detergents and sodium dodecyl sulfate. PMID- 8503175 TI - Bacteriophage PRD1 proteins: cross-linking and scanning transmission electron microscopy analysis. AB - Bacteriophage PRD1, a double-stranded DNA virus infecting Escherichia coli, has a membrane inside the protein capsid. Chemical cross-linking and scanning transmission electron microscopy showed that the multimeric major coat protein (P3) exists in a trimeric form. Cross-linking revealed, in addition, that protein P11, located between the protein coat and the membrane, exists also as a homotrimer. Minor protein P7 was associated with the major coat protein P3. Under nonreducing conditions the infectivity proteins P16 and P18 formed homomultimeric complexes which were dissociated upon addition of 2-mercaptoethanol. PMID- 8503176 TI - Characterization of defective interfering RNA components that increase symptom severity of broad bean mottle virus infections. AB - Several strains of the broad bean mottle virus (BBMV), an icosahedral tripartite plant RNA virus, which show distinct reactions on certain plant hosts have been described (K. M. Makkouk et al., Neth. J. Plant Pathol. 94, 195-212, 1988). Here we report defective interfering (DI) RNAs encapsidated in two BBMV strains from Morocco and Tunisia. While not effective in some plants, these DI RNAs exacerbated the severity of symptoms in others. The most dramatic, lethal effect of DI RNAs has been found on pea (Pisum sativum, cv. Rondo) seedlings. Sequence analysis has revealed that the DI RNAs were derived by single in-frame central deletions of 448 to 537 nt in the corresponding genomic RNA2 components. A comparison of the intensities of full-length RNA2 bands from DI molecule containing and DI molecule-deficient virion RNA preparations revealed that the DI RNAs decreased the level of RNA2 components in total RNA preparations. The differences between corresponding virion RNAs were much smaller. This suggests an interference with RNA replication. In vitro assays and an analysis of the polyribosomal RNA fractions confirmed the translational activity of DI RNAs. This paper reports the first description of natural DI RNAs in tripartite isometric plant RNA viruses. PMID- 8503177 TI - Activation and detection of a latent baculovirus resembling Mamestra brassicae nuclear polyhedrosis virus in M. brassicae insects. AB - A laboratory culture of Mamestra brassicae insects (MbLC) has been found to harbor a latent baculovirus infection. The latent virus was activated by feeding the M. brassicae larvae with either the closely related Panolis flammea nuclear polyhedrosis virus (NPV), or the distantly related Autographa californica NPV. Restriction fragment profiles of the activated virus DNA showed that it is very closely related, if not identical, to M. brassicae NPV. Polymerase chain reaction amplification of polyhedrin gene sequences demonstrated that the latent virus was present throughout the life cycle of the insect; eggs, larvae, pupae, and adults. We failed to detect the presence of a latent virus in a second culture of M. brassicae insects, obtained from the environment and only recently adapted to growth in laboratory conditions, and thus these insects acted as an effective negative control in all the PCR and activation experiments. Using PCR analysis of DNA isolated from dissected tissues of fourth instar MbLC larvae, latent virus sequences were only detected in the fat body. Cell lines established from the isolated MbLC fat body tissue were also shown to harbor the latent virus sequences and should prove useful in further studies to elucidate the mechanisms of latency and virus activation. PMID- 8503178 TI - The vaccinia virus 42-kDa envelope protein is required for the envelopment and egress of extracellular virus and for virus virulence. AB - Vaccinia virus gene B5R encodes a M(r) 42K glycoprotein that is expressed throughout infection and forms part of the envelope of extracellular virus. In this paper deletion mutants (delta B5R) lacking the B5R open reading frame (ORF) from the Western Reserve (WR) and IHD-J strains of vaccinia virus have been constructed and shown to form very small plaques compared with the wild-type viruses. This phenotype was directly attributable to loss of the B5R gene since re-insertion of this gene from WR or IHD-J into the WR mutant lacking B5R (W delta B5R) restored a normal plaque phenotype. In the latter case the failure of the revertant to form comets indicated that the nine amino acid differences in the B5R ORF between the IHD-J and WR strains of virus are not responsible for comet formation by IHD-J virus. Furthermore, the B5R deletion mutant of IHD-J (I delta B5R) still formed small comets. Despite the small plaque phenotype of the deletion mutants, normal yields of intracellular naked virus (INV) were produced. In contrast, deletion of B5R had a profound affect on the formation of the extracellular enveloped virus (EEV). Transmission electron microscopy indicated that INV particles were not wrapped by a double layer of Golgi-derived membrane and enveloped particles were not detected within the cell or on the cell surface without expression of the B5R protein. Biochemical measurement of EEV formation, by labeling infected cells with [3H]thymidine followed by cesium chloride density gradient centrifugation of particles released from the cells 24 hr postinfection, showed that only 10% of WT levels of EEV were produced by I-delta B5R. The loss of the B5R ORF caused severe attenuation in intranasally infected mice. At doses between 10(4) and 3 x 10(7) plaque-forming units there were no signs of disease in animals infected with W-delta B5R, whereas at comparable doses the WR parent virus caused significant mortalities. Finally, an ORF with 93.4% amino acid identity to vaccinia WR B5R is present in variola major virus strain Harvey and the B5R protein was shown by Western blotting to be expressed by all orthopoxviruses tested. PMID- 8503179 TI - Mutations in ORF D13L and other genetic loci alter the rifampicin phenotype of vaccinia virus. AB - Phenotypic analysis of vaccinia virus temperature-sensitive mutants identified several virus isolates that were either resistant or hypersensitive to rifampicin. Temperature-sensitive mutants 1085, 7743, 1085R, and 7743R were found to be rifampicin resistant (RifR). Each virus contained at least one mutation in ORF D13L which resulted in a change of amino acid sequence. Analysis of each point mutation by marker rescue demonstrated that mutations gly to asp at residue 80, pro to phe at 458, lys to asn at 484, and ile to val at 485 conferred the resistance phenotype, while the mutation changing ser to leu at 176 did not affect the rifampicin phenotype. Temperature-sensitive mutants C6, C17, and C43 were found to be rifampicin hypersensitive. Only C43, however, was found to contain a lesion in ORF D13L. This mutation, ser to asn at 169 was confirmed by marker rescue to confer the hypersensitive phenotype. The results presented here along with those from previous reports show that known mutations conferring rifampicin resistance cluster at the C or N-terminus of D13L while a mutation mapping at residue 169 confers rifampicin hypersensitivity. Further, the finding that the hypersensitive mutants C6 and C17 contain a wild-type D13L ORF suggests a possible role of other viral functions in the interaction of rifampicin with vaccinia virus. PMID- 8503180 TI - Characterization of the capsid associating activity of bacteriophage P4's Psu protein. AB - The Psu (Polarity suppression) protein of satellite bacteriophage P4 was first characterized as an anti-terminator of transcription termination in Escherichia coli. Psu is also a structural component of mature P4 capsids, where it is present as a decoration protein. Psu is located externally on the capsid surface, and it appears to protect the capsid from loss of DNA through the capsid shell. The ability of Psu to specifically bind to the P4 capsid appears not to be dependent on any P4 specific components such as the capsid protein cleavage products h1 and h2, or P4 DNA. We suggest that Psu binds to the P4 capsid as a result of the special structure of the hexamers in the P4 capsid. PMID- 8503181 TI - Capsid localization of the bacteriophage P4 Psu protein. AB - In addition to its polarity-suppressing activity, the Psu protein of bacteriophage P4 also serves to stabilize the capsid against heat treatment and binds externally to the phage capsid. However, the heat stability is lost upon purification of the virus, indicating a loss of Psu protein from the capsid. By using three-dimensional reconstruction from cryo-electron micrographs of P4 psu1 amber mutants lacking Psu, and of P4 virions, which have been saturated with Psu protein to regain heat stability, we have determined the position of this protein on the virus surface. Our results are consistent with the hypothesis that the function of Psu is to stabilize the hexameric capsomer assembly. PMID- 8503182 TI - Avian reovirus proteins associated with neutralization of virus infectivity. AB - Monoclonal antibodies against two virion proteins of the RAM-1 strain of avian reovirus neutralized virus infectivity; antibody against a 124-kDa (lambda B) protein caused broadly specific neutralization and antibody against a 39-kDa (sigma C) protein caused neutralization of greater type-specificity. The neutralizing activity of the monoclonals also exhibited host cell specificity: antibodies against the lambda B protein inhibited virus infectivity in Vero cells and not chicken kidney cells; one monoclonal antibody against the sigma C protein neutralized virus in only chicken kidney cells, whereas two other monoclonals against the sigma C protein neutralized virus in both Vero and chicken kidney cells but had greater neutralizing activity in Vero cells. PMID- 8503183 TI - Functional analysis of cymbidium ringspot virus genome. AB - Genomic RNA of cymbidium ringspot tombusvirus (CyRSV) contains five large open reading frames (ORFs). The two 5' proximal ORFs encode proteins of 33 and 92 kDa and the three 3' proximal ORFs encode proteins of 41, 22, and 19 kDa. In addition, a small reading frame encoding a protein of 4 kDa was recently observed by computer analysis of the 3' nontranslated region of CyRSV and other tombusvirus RNAs (ORF 6). The function of putative gene products was investigated with the use of several mutants. Mutants in ORFs 1 and 2 were not viable indicating that both 33- and 92-kDa proteins are required for replication. Deletion of a large portion of the coat protein gene, encoding a 41-kDa protein, did not prevent replication of viral RNA and cell-to-cell movement, but interfered severely with long-distance translocation. No virus particles or viral RNA could be detected in inoculated or upper leaves of plants inoculated with transcripts obtained from mutants not expressing the 22-kDa protein. However, replication and encapsidation occurred normally in inoculated protoplasts indicating that this gene product is a transport protein. Conversely, no role could be assigned to putative gene products of ORF5 (19-kDa protein) and ORF6. It was also shown that factors other than gene expression can influence the replication of RNA mutants, probably due to instability of RNA molecules. PMID- 8503184 TI - Characterization of avian reovirus-induced cell fusion: the role of viral structural proteins. AB - Cell fusion induced by avian reovirus was analyzed using virus strain FC and Vero cells. One-step growth curves showed that cell fusion was directly associated with viral replication. Cell fusion occurred most efficiently at basic pH (8.0 8.5) and fusion from without could not be demonstrated. Actinomycin D, at low concentrations, increased cell fusion, and cycloheximide prevented cell fusion, indicating that viral protein(s) were responsible for the induction of cell fusion. Immunofluorescence tests indicated that viral proteins were present on the infected cell surface. Radioimmuno-precipitation identified structural proteins mu 2C and sigma 2 as predominant viral protein species present on the infected cell surface. Cell fusion was inhibited by virus-specific antisera, suggesting that mu 2C and/or sigma 2 present on the infected cell surface were involved in the induction of cell fusion. Trypsin and chymotrypsin treatment of purified viruses cleaved both mu 2C and sigma 2 proteins, but generated different cleavage products with each protein. The addition of trypsin to the culture media following infection increased cell fusion, whereas chymotrypsin treatment decreased cell fusion. The opposite effects of trypsin and chymotrypsin on the cell fusion, together with the different specificities of these two proteases in cleavage of mu 2C and sigma 2 proteins, further suggest that the cell surface associated mu 2C and/or sigma 2 are involved in the syncytium formation. PMID- 8503185 TI - DNA B facilitates, but is not essential for, the spread of abutilon mosaic virus in agroinoculated Nicotiana benthamiana. AB - Full-length dimers of both DNA A and DNA B of Abutilon mosaic virus have been constructed. These constructs are not infectious when inoculated into Nicotiana benthamiana as DNA; however, an infection could be obtained using the method of agroinoculation. Symptom induction required both DNA molecules but agroinoculation with DNA A alone resulted in virus spread in the majority of plants. Mutations were made in both of the open reading frames of DNA B. Coagroinoculation of wild-type DNA A and mutant B showed that DNA B is necessary for a full infection and symptom induction. Furthermore, it was shown that mutations in DNA B inhibit the ability of DNA A to spread independently. A normal infection was obtained following coagroinoculation of both DNA B mutants and wild type DNA A. PCR analysis of DNA extracted from these plants showed that the infection was brought about by complementation rather than recombination. PMID- 8503186 TI - An influenza virus temperature-sensitive mutant defective in the nuclear cytoplasmic transport of the negative-sense viral RNAs. AB - An influenza A virus mutant ts-51, which contains a temperature-sensitive (ts) defect in the genome encoding the M1 and M2 proteins, was characterized. Nucleotide sequencing of the M segment revealed a predicted single amino acid change of phenylalanine to serine at amino acid position 79 in the M1 protein. The nuclear-cytoplasmic transport of the negative-sense viral RNAs (vRNAs) was then investigated using an in situ hybridization technique. At 6 hr after the ts 51 virus infection, approximately 95% of the vRNAs were accumulated in the nucleus at a non-permissive temperature, when approximately 50% of the vRNAs were transported into the cytoplasm in the wild-type virus-infected cells. The M1 protein of the ts-51 virus was also accumulated in the nucleus under the same conditions. Therefore, the M1 protein of the ts-51 virus may be associated with the vRNPs, but the possible M1-vRNP complex thus formed was defective in the nuclear-cytoplasmic transport and the single amino acid change in the M1 protein was responsible for this defect. PMID- 8503187 TI - Antigenic and molecular properties of Murayama virus isolated from cynomolgus monkeys: the virus is closely related to avian paramyxovirus type 2. AB - A new virus that belonged to a member of paramyxovirus was isolated from cynomolgus monkeys showing respiratory disorders about 20 years ago and was named Murayama virus (MrV). Interestingly, it showed no serological relationship with the mammalian paramyxoviruses tested. On the other hand, it was related to Yucaipa (YuV) and Bangor virus (BaV) belonging to avian paramyxovirus type 2 (PMV2). In analysis using anti-MrV monoclonal antibodies, MrV showed the closest relationship with YuV, and furthermore some conserved epitopes were found among avian paramyxovirus, MrV, YuV, BaV, and Newcastle disease virus (NDV). Subsequently, the nucleotide sequences of the F and HN genes of MrV were determined. In comparison with the deduced amino acid sequence of MrV and other paramyxoviruses, MrV showed the highest homology with NDV and higher similarity to HPIV2 group rather than to HPIV1 group. The present study clearly indicates that MrV belongs to PMV2 adapting to monkeys. PMID- 8503188 TI - Conformational perturbation of the envelope glycoprotein gp120 of human immunodeficiency virus type 1 by soluble CD4 and the lectin succinyl Con A. AB - We have studied perturbation of the gp120/gp41 envelope complex of HIV-1 in the presence of the mannose-specific lectin succinyl Con A (SC) and compared the effect with that observed in the presence of soluble CD4 (sCD4). SC did not inhibit the binding of gp120 to CD4. Both sCD4 and SC inhibited syncytium formation induced by HIV-1-infected Molt3/HIV-1IIIB cells. The infectivity of HIV 1 was markedly reduced when the virions were preincubated with SC or when SC was mixed simultaneously with virus and cells. The conformation of gp120 was altered in the presence of SC as evidenced by an increased susceptibility of the principal neutralizing epitope (V3 loop) to thrombin digestion. SC treatment of [35S]-methionine-labeled virions derived from Molt3/HIV-1IIIB cells resulted in the dissociation of gp120 from the viral membrane. The effect was less pronounced than that observed with sCD4. These results suggest that although interacting with different regions of gp120, the mannose-specific lectin alters the conformation of the glycoprotein in a manner similar to that induced by sCD4, causing destabilization of the gp120/gp41 complex. PMID- 8503189 TI - Mutations in the protease gene of human immunodeficiency virus type 1 affect release and stability of virus particles. AB - The expression of the pol gene of human immunodeficiency virus type 1 (HIV-1) occurs by a ribosomal frameshift between the gag and the pol genes. The Gag-Pol polyprotein is produced at levels of 5 to 10% of that of the Gag protein, and is incorporated into virions to provide the viral protease, reverse transcriptase, and integrase which are essential for replication. The mechanism(s) by which the Gag-Pol polyprotein are targeted to the HIV virion is unknown, although it is believed to be via an interaction with the Gag protein. To further explore the mechanism by which the Gag-Pol polyprotein is incorporated into virions, we have constructed a mutation which changes an aspartic acid in the protease active site to asparagine (pHXB2pro-); a four-amino-acid insertion into the protease gene (pHXB2Smal); and insertion of translational termination codons in the protease gene following the gag gene (pHXB55). Transfection of these proviral genomes into COS-1 cells resulted in intracellular expression of only Pr55gag, demonstrating the inactivation of the viral protease. The expression of Pr55gag was evident in cells transfected with pHXB2pro- during a short pulse and first 3 hr of chase period, whereas at later times the intracellular levels of Pr55gag were greatly reduced. In contrast, the intracellular Pr55gag expressed from transfection of pHXB2Smal or pHXB55 were evident even after 6- or 12-hr chase times. To ascertain the effects of the mutations on the assembly and release of viruslike particles, the supernatants from the transfected cells were analyzed for the presence of Pr55gag. The release of Pr55gag from cells transfected with pHXB2pro- occurred as early as 1 hr following chase period, and increased for up to 3 hr. In contrast, reduced levels of Pr55gag were detected in the medium from cells transfected with pHXB2Smal or pHXB55. Subcellular fractionation studies demonstrated that the Pr55gag expressed from transfection of pHXB2pro- was rapidly targeted to intracellular membranes, while the majority of the Pr55gag expressed from transfection of pHXB2Smal or pHXB55 was distributed evenly between the cytoplasm and membrane fractions. Finally, the released viruslike particles obtained from the transfection of proviral genome pHXB2pro- were stable to mild detergent treatment, whereas particles obtained from transfection of pHXB2Smal and pHXB55 were relatively unstable. These results demonstrate that subtle changes in the Gag-Pol polyprotein of HIV-1 can have significant effects on the assembly and physical stability of the released virus. PMID- 8503190 TI - The majority of simian immunodeficiency virus/mne circle junctions result from ligation of unintegrated viral DNA ends that are aberrant for integration. AB - SIV/Mne circle junctions were amplified by the polymerase chain reaction (PCR) and cloned in a bacterial plasmid. Sequence analysis of clones isolated from 11 independent PCRs reveals that the start site for plus DNA synthesis is 5' ACTG. . ., and thus an asymmetric cleavage must occur during viral integration. In addition, most of the sequences found resulted from the ligation of aberrant proviral DNA ends that were apparently generated by priming errors, primer removal errors, or integrase processing errors. The results suggest that in this virus, as in Moloney murine leukemia virus, two good ends may be required for efficient integration. PMID- 8503191 TI - A molecular clone of HIV-1 tropic and cytopathic for human and chimpanzee lymphocytes. AB - Previous studies of HIV-1 replication in chimpanzee lymphocytes have been limited to a small number of virus isolates which generally replicated poorly and without cytopathic effect. Here, we describe an HIV-1 provirus (SG3), cloned as a single proviral unit, which replicates more efficiently in chimpanzee than in human lymphocytes, resulting in syncytium formation and cell death. This provirus also replicates efficiently and with extraordinary cytopathic effect in immortalized human T-cell lines. The SG3 genome was completely sequenced and found to contain all genes typical of HIV-1 with the exception of vpu. Phylogenetically, SG3 is representative of North American/European strains of HIV-1 and shows no greater similarity to SIVCPZ in its envelope sequence than do other HIV-1 strains. Pilot studies indicate that SG3 can infect and replicate in chimpanzees and SCID-hu mice in vivo following intravenous or intrathymic inoculation. The SG3 proviral clone, because of its replication efficiency in human and chimpanzee cells and its complete molecular description, represents a new virologic reagent for the coordinated molecular analysis of HIV-1 replication and pathogenesis in relevant animal model systems. PMID- 8503192 TI - Infection with Moloney murine sarcoma virus inhibits myogenesis and alters the myogenic-associated (2'-5')oligoadenylate synthetase expression and activity. AB - Infection of rat skeletal muscle cultures on the first or second day in vitro with Moloney murine sarcoma virus (MSV) led to the arrest of myotube formation and to inhibition of both the synthesis of the muscle-specific proteins acetylcholine receptors and creatine kinase and the expression of the myosin light chain-2. Mos-specific RNA transcripts were readily detected at 1 day after infection indicating that viral genes were expressed in infected cells. In parallel, the expression of the cell growth-associated gene--c-myc--in uninfected muscle cultures was drastically reduced with time, while in MSV-infected myoblasts, the amount of c-myc-specific RNA transcripts gradually increased with time after infection. Under these conditions we could demonstrate that the interferon-induced gene (2'-5')oligoadenylate synthetase (2-5A synthetase) was transiently activated in uninfected muscle culture reaching a peak activity on the third day. Infection of myoblasts with murine leukemia virus did not alter the pattern of 2-5 synthetase activity observed in uninfected cells. However, infection with MSV on the second day led to a slight reduction in activity followed by a significant increase on the sixth and seventh day. Similarly, 2-5A synthetase gene expression was down-regulated with time in culture in uninfected myoblasts while re-expressed between the fourth and seventh days in MSV-infected cultures. PMID- 8503193 TI - Localization and biochemical characterization of alfalfa mosaic virus replication complexes. AB - Replication complexes were isolated from alfalfa mosaic virus-infected tobacco protoplasts. Most of the RNA-synthesizing activity appears to colocalize with the intact chloroplasts upon sucrose-gradient centrifugation of cellular homogenates. Further analysis of these replication complexes showed that the enzyme is strongly associated with the outside of the chloroplasts, the endogenous template being well protected against ribonuclease action. RNA polymerase activity is sensitive to protease treatment of intact chloroplast fraction showing that an essential part of the enzyme complex is facing the in vitro medium, and probably the cytosol in vivo. PMID- 8503194 TI - Transient and sustained components of the pupillary responses evoked by luminance and color. AB - That the pupil reacts to changes in luminance and color, as well as to spatial features in the retinal image raises questions about whether phasic and tonic and/or color and luminance visual pathways project to the pretectal pupillomotor neurons. The present study compares pupillary responses evoked by heterochromatic and achromatic luminance increments to investigate whether the pupillary responses evoked by color and by luminance are independent of one another. Principal component analysis is used to examine the constituents of the pupil responses. The results support the belief that the visual input to the pupillomotor system is organized into phasic and tonic (but not necessarily independent color and luminance) pathways. PMID- 8503195 TI - Dissociation of discrimination thresholds for time to contact and for rate of angular expansion. AB - It is well known that, if a rigid sphere is moving at constant speed towards the eye along the line of sight then, for small values of theta, T = theta/theta, where T is the time to contact, theta is the instantaneous angular size and theta is the rate of increase of angular size. We describe a rationale and an experimental procedure for demonstrating empirically when subjects base discrimination of time to contact on trial-to-trial variations of (theta/theta) rather than on variations of theta or on variations of delta theta (the change of angular size during a presentation). Discrimination threshold for the ratio (theta/theta) was 0.070-0.13, and was independent of mean time to contact over a range of at least T = 1.0-4.0 sec. We conclude that the human visual pathway contains a mechanism that is sensitive to the ratio (theta/theta) rather independently of the values of theta and theta. Using a different procedure we demonstrated empirically that subjects based discriminations of rate of expansion on trial-to-trial variations of theta rather than variations of time to contact or on variations of delta theta. Discrimination threshold for rate of expansion was 0.85-0.14, and was independent of mean time to contact over a range of at least T = 1.0-4.0 sec. We conclude that the human visual pathway contains a mechanism that is sensitive to rate of expansion rather independently of time to contact or absolute change in size. When rate of expansion and time to contact were both available as cues, discrimination threshold was on average lower than when only one of the two cues was present. We conclude that there is some summation of the two cues. Our data can be explained by a small modification to a model previously put forward to account for data on threshold elevations and aftereffects caused by adapting to changing-size stimulation. This model incorporates a filter that is strongly activated by isotropic, homogeneous two dimensional expansion of the retinal image and whose output is inversely proportional to time to contact (i.e. the more urgent the demand for evasive action, the stronger the output of the filter). PMID- 8503196 TI - The dimensionality of texture-defined motion: a single channel theory. AB - We examine apparent motion carried by textural properties. The texture stimuli consist of a sequence of grating patches of various spatial frequencies and amplitudes. Phases are randomized between frames to insure that first-order motion mechanisms directly applied to stimulus luminance are not systematically engaged. We use ambiguous apparent motion displays in which a heterogeneous motion path defined by alternating patches of texture s (standard) and texture v (variable) competes with a homogeneous motion path defined solely by patches of texture s. Our results support a one-dimensional (single-channel) model of motion from-texture in which motion strength is computed from a single spatial transformation of the stimulus--an activity transformation. The value assigned to a point in space-time by this activity transformation is directly proportional to the modulation amplitude of the local texture and inversely proportional to local spatial frequency (within the range of spatial frequencies examined). The activity transformation is modeled as the rectified output of a low-pass spatial filter applied to stimulus contrast. Our data further suggest that the strength of texture-defined motion between a patch of texture s and a patch of texture v is proportional to the product of the activities of s and v. A strongly counterintuitive prediction of this model borne out in our data is that motion between patches of different texture can be stronger than motion between patches of similar texture (e.g. motion between patches of a low contrast, low frequency texture 1 and patches of high contrast, high frequency texture h can be stronger than motion between patches of similar texture h). PMID- 8503197 TI - Judging an object's velocity when its distance changes due to ego-motion. AB - This paper examines how one accounts for ones own movements when judging the velocity of a moving object, with emphasis on ego-motion perpendicular to the direction in which the object is moving. The "object" was a square that was tracked with smooth pursuit eye movements as it moved horizontally across a computer screen. Half-way through the presentation, the image on the screen changed in a manner simulating ego-motion in depth. At the same time, the speed with which the square moved across the screen also changed. Subjects were asked to report whether the target moved faster, at the same speed, or more slowly after the simulated ego-motion. The change in target velocity that was required for it to appear to continue to move at the same speed was determined for simulations containing different aspects of the information that is normally at our disposal. The results show that the change in the size of the image of the target, the expansion or contraction of the image of the surrounding, and differences in target motion between the two eyes (giving rise to vergence eye movements), all contribute to rendering the perceived object velocity independent of ego-motion. PMID- 8503198 TI - Visibility, timing and vernier acuity. AB - To investigate the relationship between contrast detection and vernier acuity for abutting targets, the effects of varying target exposure duration (12-2000 msec) on vernier and contrast detection thresholds for long, thin lines and sinusoidal gratings (1 and 8 c/deg), were measured. Vernier thresholds decreased with both increasing exposure duration and increasing target contrast. Predictions made for equally visible targets show that the effect of exposure duration on vernier thresholds is almost completely accounted for by its effect on target visibility. Vernier thresholds and contrast detection thresholds for line targets were also measured in the presence of a spatiotemporal mask, for different exposure durations. Again, once the effect of this mask on target visibility was accounted for, there was virtually no remaining effect of exposure duration on vernier thresholds. The results of these experiments suggest that similar spatial mechanisms mediate both contrast detection thresholds and vernier thresholds for abutting targets; and that the processes involved in target detection and the extraction of relative position information are limited by the same factors. PMID- 8503199 TI - Visibility, luminance and vernier acuity. AB - To assess the role of quantal limitations and target visibility on vernier acuity, we measured line detection thresholds and vernier thresholds for abutting dark line targets on a uniform background, for a range of retinal illuminance levels and target contrasts. Measurements were made for stimuli presented at the fovea, and at a retinal eccentricity of 2.5 deg. Although the relationship is truly curvilinear, line detection thresholds and vernier thresholds using targets of a fixed contrast, follow a square-root dependence on retinal illuminance over a significant portion of the illuminance range. Once the effect of retinal illuminance on line detection thresholds has been accounted for, there is little further effect of retinal illuminance on vernier thresholds, at least for visibility levels of up to five times the contrast detection threshold. This finding suggests that the spatial mechanisms which mediate changes in the detection threshold and vernier thresholds for abutting targets are similar, and are limited by the same sources of noise. Vernier thresholds for these thin line targets are approximately inversely proportional to target contrast for both retinal loci, and at all retinal illuminance levels tested. However, vernier thresholds for a constant visibility target are always lower for foveal than for eccentric stimuli, even after the effects of increased spatial pooling with increasing eccentricity are accounted for. PMID- 8503200 TI - Visibility and vernier acuity for separated targets. AB - The purpose of this study was to investigate the roles of the putative "spatial filter" and "local sign" mechanisms in determining line vernier thresholds for a range of target separations, using stimulus contrast or visibility as a tool. In Expt 1, the effects of varying target contrast and exposure duration on vernier thresholds for lines separated by 90 min arc, where the reference line was fixated, were measured. Contrast thresholds for the nonfixated test line were also measured, so that the role of its visibility in limiting vernier thresholds could be assessed. Vernier thresholds decreased almost proportionally with increasing contrast only until the visibility of the test line reached about 3 times the contrast detection threshold, regardless of exposure duration. At higher visibility levels, vernier thresholds were virtually independent of target contrast. In Expt 2, the effects of varying target contrast on vernier thresholds for a range of target separations (2-90 min arc) were measured using a 250 msec exposure duration. Vernier thresholds for abutting lines and for those separated by 2 min arc, decreased with target contrast until about 30 times the test line's contrast detection threshold. However for lines separated by 4 min arc or more, they were only weakly dependent on target contrast at much lower visibility levels. We propose that for very close separations vernier thresholds are limited by the contrast response properties of spatial filters. For separations of 4 min arc or more, thresholds appear to be limited by the positional uncertainty of the test line, which increases with eccentricity. PMID- 8503201 TI - Theta motion: a paradoxical stimulus to explore higher order motion extraction. AB - Apparent motion stimuli of increasing complexity have been applied to analyse the mechanisms underlying visual motion perception. In the present paper it is investigated how motion detectors respond to three classes of stimuli which are realized as random-dot kinematograms. (i) In the most conventional stimuli, Fourier motion, a group of dots is displaced coherently in a random-dot pattern. (ii) In drift-balanced motion stimuli a bar made of static random dots is shifted in front of another random-dot pattern. (iii) In the novel class of stimuli, theta motion, an object which is exclusively defined by dot motion into one direction, is moving itself into the opposite direction. It is shown in psychophysical experiments that human observers perceive the direction of object motion in all three classes of stimuli. Simple motion detectors, however, only extract the motion direction of the object in the case of Fourier stimuli, and in the case of drift-balanced stimuli, if a nonlinear preprocessing is assumed. Any of the model alternatives discussed so far just detects the moving dots but not the object in a theta-stimulus, as is illustrated by a combinatorial analysis using a simplified version of a motion detector of the correlation type, which operates on a discrete time scale and takes only discrete values. In order to account for the detection of theta-motion, a model consisting of two hierarchical layers of motion detectors is developed, and simulated for conditions as used in the psychophysical experiments. The perception of theta-motion and the two-layer model is discussed in relation to psychophysical data and theoretical considerations from the literature, to try to incorporate the proposed two-layer model into a general scheme of visual motion processing. PMID- 8503202 TI - [Taxonomic study on strain 1254 and its mutant 113]. AB - The mutant 113 was obtained from a natural non-antibiotic producing Streptomyces sp. 1254 by UV irradiation. It produced a group of novel anthracycline compounds designated mutactimycins. Strain 1254 was placed in the genus Streptomyces on the basis of its morphological characteristics and chemical properties of cells. According to Williams's numerical taxonomical data based on more than 50 physiological tests of a total of 375 type strains, the strain 1254 is considered to be more resemble to S. omiyaensis in the cluster of S. exfoliatus. The whole cell hydrolysate of mutant 113 contains DL-DAP, arabinose, galactose and rhamnose, but its cell envelope does not contain mycolic acids. Comparing with all genera of cell chemotype IV without mycolic acids and with Sacchrothrix which contains taxonomically significant rhamnose, mutant 113 shows differences with them respectively on FA composition or MK and PL patterns. The conclusion we can draw now is that mutant 113 doesn't belong to the same genus Streptomyces as its parent strain 1254 does, and is more close to the genus Sacchrothris. PMID- 8503203 TI - [Studies on insecticidal ingredients from culture supernatant of Bacillus thuringiensis]. AB - Studies on the insecticidal activity of culture supernatant of Bacillus thuringiensis var. kurstaki HD-1, by centrifugation, column chromatography, protein sequence determination, bioassay and other methods. Found that insecticidal activity of culture supernatant appeared on synchronism with cells lysis. Main insecticidal ingredients of culture supernatant is toxin protein of 60 kilodaltons (kDa). Analyse hat purified the toxin protein, we find that its amino acid composition was similar with 135-kDa P1 protein, and its sequence of N terminal 18 amino acid was same with that of part of the P1 protein. The results presented here provided that the toxin protein was the same source with the P1 protein. Further found that supernatant have synergizing action on the sediment of culture. PMID- 8503204 TI - [A study on classification of Xanthomonas by isoelectric focusing]. AB - Studying Xanthomonas strains of 4 species and 29 pathovars by isoelectric focusing, it was shown that the protein patterns were very different among the species and pathovars. Through cluster analysis of IEF date, it was found that the protein pattern differences among certain pathovars were no fewer than that among the species. It revealed that some pathovars could become to be species. There were few differences of 6 protein bands among X. campestris pv. cerealis, X. campestris pv. undulosa and X. campestris pv. hordei which cause bacterial black cheff, so the classification of the three pathovars need to be re considered. It also showed that isoelectric focusing could be used to classify Xanthomonas below species. PMID- 8503205 TI - Decade of the brain: 1990-2000 contemporary issues in the brain-mind phenomena. PMID- 8503206 TI - Recent developments in low-cost screening and assessment of childhood disabilities in Jamaica. Part 1: Screening. AB - This paper reviews and summarises the requirements and criteria for the screening of childhood disabilities. It reviews recent advances in research carried out in Jamaica and outlines available techniques for the screening of cognitive, motor, speech, hearing and visual disabilities and fits. The availability of validated, simple, low-cost techniques that can be used by community workers facilitates the conduct of surveys for the planning of programmes and the identification of cases for rehabilitation. PMID- 8503207 TI - Use by visitors of the services of the Queen Elizabeth Hospital, Barbados, W.I. AB - This paper analyses data for 1990 culled from the medical records of the Queen Elizabeth Hospital, Barbados and examines the use of inpatient and emergency services by visitors to Barbados. The 473 visitors admitted represented 2.1% of all admissions. The records of 425 contained information on country of origin: 145 were from non-Caribbean and 280 from Caribbean countries. The distribution by country of non-Caribbean visitors was the same as that of regular tourist arrivals--the majority came from the USA. Canada and the UK. Caribbean visitors represented 14.4% of the tourists, but accounted for 65.9% of visitor admissions. Non-Caribbean visitors were 85.6% of tourists, but 34.1% of admissions. Young patients predominated among Caribbean, and older patients among non-Caribbean. Accidents, cardiovascular disease, alcohol-related illnesses and near drowning were commoner in the non-Caribbean visitors, while cancer and obstetrical/gynaecological problems were commoner in Caribbean visitors. Seven per cent of visitor admissions went to the Intensive Care Unit as against 0.15% of other patients. The average hospital stay of visitors was 11.7 days compared with 7.0 days for Barbadians. There were 898 visitors treated in the Accident and Emergency Department and the commonest problems were lacerations, abrasions and infections. The UK provided most of these patients. These data show that there is appreciable visitor use of the public health services. Non-Caribbean visitors use them because they fall ill on holiday, but many Caribbean visitors may come specifically for health care. The cost to the Barbadian health service is not insignificant: at the 1990 estimated bed-day cost of Bds$250, it represents a cost of Bds$1.1 million per annum to the Government for inpatient services alone, or 2% of total hospital costs. PMID- 8503208 TI - Significant changes in gastrointestinal tract parasitic infections in children of St. Kitts over the 9-year period 1982-1991. AB - When 239 (1982) and 361 (1991) five- and nine-year-old children in St. Kitts were assessed for the presence of parasitic infections, there were significant reductions in the prevalence of trichuriasis from 83% to 58%, of ascariasis from 24% to 8.6% and of giardiasis from 15% to 9.4%. Anthelminthic use, which appeared to be the most important responsible intervention tool, remained roughly at the same level at 59-51%. However, the types of anthelminthics used changed over the period. Piperazine citrate, which was used by 66% in 1982, only had 35% usage in 1991. Albendazole which was not used at all in 1982 was taken by 32% of the children in 1991 and at the same time use of laevo-tetramisole increased by 20% from 14%. Suggestions are made for an island-wide mass intervention programme to manage parasitic infections. PMID- 8503209 TI - Is adolescent pregnancy hazardous? AB - A study of the pregnancy outcome in 3320 teenagers revealed a low incidence of pre-eclampsia and anaemia and high rates of eclampsia, prematurity and low birthweight. The perinatal loss was 2.2 per cent and there was one maternal death. A comprehensive programme designed to improve antenatal surveillance is recommended for adolescents. PMID- 8503210 TI - Inguinal hernia in children. AB - Two hundred and seventy-one cases of inguinal hernias and hydrocoeles in children treated at the University Hospital of the West Indies over a five-year period have been reviewed. The dominance of the boys and the right side is borne out. The younger infant has the highest risk of incarceration which is more common in boys and in right-sided hernias. Females with inguinal hernia were screened for testicular feminization and none was found. There were three girls with hydrocoeles of the Canal of Nuck. The incidence of metachronous presentation of contralateral hernia occurred only in 6.6% of cases. When routine exploration of the contralateral side was undertaken in 5.2% of cases, a hernial sac was found only in less than half of them. These findings support the present policy of not routinely exploring the opposite side in unilateral inguinal hernias. Herniotomy was adequate for 92.6% of cases. Herniorrhaphy was reserved for large hernias and sliding hernias. Complications were minor and infrequent. Recurrence was seen in only one case. One testicular atrophy occurred following incarceration. Eight-six per cent of these children were managed as day cases. In-patient management was required when the hernia was complicated or when there were associated other medical conditions. PMID- 8503211 TI - Portal vein thrombosis in a child with homozygous sickle-cell disease. AB - A 13-year-old boy with homozygous sickle-cell (SS) disease died suddenly at home following a short history of abdominal pain. Autopsy revealed venous thrombosis of the hepatic, portal, superior mesenteric and splenic veins. Venous thrombosis is rare in SS disease and thrombosis of mesenteric vessels is most frequently seen in chronic myeloproliferative disorders. Its occurrence in SS disease raises the possibility of a common pathogenesis and adds another pathology to the causes of the abdominal painful crisis. PMID- 8503212 TI - Thoracic outlet syndrome. AB - A case of thoracic outlet syndrome (TOS) treated at the University Hospital of the West Indies, Jamaica, is presented. The diagnosis, investigation and management of TOS are discussed. PMID- 8503213 TI - The university, the private sector and the health of the Caribbean people. PMID- 8503214 TI - Benign colovesical fistulae. AB - Two successfully treated cases of benign colovesical fistula are presented. The condition should be suspected whenever patients with colorectal disease develop urinary symptoms. Flexible colonoscopy and a lateral abdominal X-ray should be the initial investigations; but barium enema, cystoscopy and, rarely, CT scan may be necessary to confirm the presence of a colovesical fistula. Patients should be managed conservatively during the acute phase, and then be treated definitively by a single-stage bowel resection. Simple closure or resection and closure is used for the bladder-defect. PMID- 8503215 TI - Cavernous haemangioma of the duodenum. A rare cause of gastrointestinal bleeding. AB - Vascular malformations (VMs), including haemangioma, of the upper gastrointestinal tract, are rare causes of bleeding. Bleeding from these lesions is often recurrent and diagnosis is often delayed for months to years. A patient with severe, recurrent upper gastrointestinal bleeding requiring repeated hospitalization and blood transfusions is presented. Upper endoscopy, barium meal and small bowel enteroclysis were negative. Selective mesenteric angiography revealed a VM in the second part of the duodenum. Segmental resection of the duodenum was performed and microscopical examination showed cavernous haemangioma. VM should be considered in patients with recurrent gastrointestinal bleeding and negative conventional investigations. Mesenteric angiography may be the only investigation which will identify these lesions. Results after excision are excellent. PMID- 8503216 TI - Fatal metastatic calcification in a patient with HTLV-1-associated lymphoma. AB - Metastatic calcification of the heart, lungs and kidneys is described in a 42 year-old male who had an HTLV-1-associated lymphoma. This fatal complication of HTLV-1-associated lymphoma has been infrequently reported, and the case in question is the first to be recorded in the Caribbean, where HTLV-1 is common. Aggressive therapy of hypercalcaemia should be instituted early in its genesis in these lymphomas, so as to avoid its fatal outcome. PMID- 8503217 TI - Haemothorax and ascites associated with endometriosis. AB - A young patient with pleuroperitoneal endometriosis presented with an haemorrhagic pleural effusion. Two years later, she developed massive ascites which resolved after treatment with oral Danazol and Depo-Provera injections. PMID- 8503218 TI - Measles elimination in the Caribbean: surveillance update. PMID- 8503219 TI - Cholera update. PMID- 8503220 TI - Declaration of Olympia on nutrition and fitness. May 26, 1992. PMID- 8503221 TI - Exercise and mood. PMID- 8503222 TI - Vitamin requirements for increased physical activity: vitamin E. PMID- 8503223 TI - Principles of athletes' nutrition in the Russian Federation. PMID- 8503224 TI - Exercise and protein metabolism. PMID- 8503225 TI - Carbohydrate needs of elite athletes. PMID- 8503226 TI - Contribution of fats and fatty acids to performance of the elite athlete. PMID- 8503227 TI - The Body Profile Analysis System (BPAS) to estimate ideal body size and shape: application to ballet dancers and gymnasts. PMID- 8503228 TI - Nutritional and fitness considerations for competitive wrestlers. PMID- 8503229 TI - Energy needs of the elite athlete. PMID- 8503230 TI - Jockeys and their practices in South Africa. PMID- 8503231 TI - Management of gestational diabetes. AB - The author reports on the antenatal care and delivery of 409 pregnant women with gestational diabetes. Normal glucose levels were achieved by diet in 239 patients and by diet + insulin in 170 patients. In the course of setting the diet the author's aim was to maintain the 24 hour glucose profile between 3.5 and 6.5 mmol/l. Blood glucose values were found to be higher in patients treated by diet only, as compared with those who received insulin. The difference was, however, not significant. Of the complications of pregnancy, EPH gestosis, weak uterine contractions during labor, and intrauterine asphyxia were most frequently encountered. It is to be noted that the mean birthweight (3620 g) of newborns of very obese mothers was higher than that of the controls (3380 g), and the reported fetopathic cases (13) were also found in this group. Among the patients studied by author premature delivery occurred in 3.42%, and perinatal mortality in 1.2% of the cases. PMID- 8503232 TI - How to treat the infertility caused by sperm antibodies? PMID- 8503233 TI - [Effect of body build on menstrual cycle]. AB - The relation between 21 absolute body dimensions as well as 20 anthropometric indices and the length as well as the regularity of the menstrual cycle have been investigated in 156 patients of the hormone ambulance of the I. Universitats Frauenklinik in Vienna. It turned out, that the length as well as the regularity of the menstrual cycle significantly negatively with the amount of the subcutaneous fat tissue. With an increasing amount of adipose tissue, the cycle became shorter and more regular. The importance of the subcutaneous fat tissue as a secondary hormonal gland has been discussed as one cause for these significant connections. Regarding the length- and height dimensions and the menstrual cycle patterns, no statistically significantly relationship could be observed between these two trait system. This is also true for the relationship between body built and the bleeding duration. PMID- 8503234 TI - An imbalance between the excretion of thromboxane and prostacyclin metabolites in women after the menopause. AB - An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women. Because thromboxane A2 is both vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of atherosclerosis. Its effects are antagonized by prostacyclin. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in women after menopause. We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 106 postmenopausal women and in 105 premenopausal women, both aged 45 to 55 years. The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in postmenopausal women whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased. Whether the imbalance in the release of these mediators is a cause or a result of atherosclerosis is unknown, but it may play a part in the development of this disorder. PMID- 8503235 TI - [The diagnostic value of routine prolactin determination in sterility patients]. AB - In the year 1976 an expert group of the WHO recommended to determine serum prolactin routinely at the beginning of any infertility work-up. We investigated whether this recommendation is still tenable. Serum-prolactin was determined in 292 patients of an infertility clinic. In 33 women serum-prolactin exceeded the upper limit of the norm (600 microIE/ml). In 11/33 cases only, hyperprolactinemia was found to persist. This shows that the routine determination of prolactin in such cases appears to be of questionable value. PMID- 8503236 TI - Pregnancy and delivery in women aged 35 years and over. AB - At the Medical Centre Department of Gynaecology and Obstetrics in Sibenik there were 26 116 deliveries over the 1970-1991 period, of which 1502 (5.75%) occurred in women aged 35 years and older. Among them 254 (0.97%) were primiparas, 1074 (4.11%) multiparas (two to four deliveries) and 174 (0.6%) grand multiparas (five deliveries and more). The control group consisted of 7920 primiparas, 7920 multiparas (two to four deliveries) and 80 grand multiparas (five deliveries and more) aged 20 to 34 years. There was no difference for occupation between the two groups (P > 0.05), whereas rural women (59.5%), unmarried women (4.2%), women with spontaneous (21.0%) or induced abortions (23.3%) were more common in the study group (P < 0.001). No antenatal visit received 5.9% and 1.8% (P < 0.001) in the study and control groups, respectively; the mean number of antenatal visits was 6.05 +/- 3.20 and 6.26 +/- 3.12, respectively (t = 2.41, P < 0.05). Threatened abortion (16.8%), EPH gestosis (9.5%), cervical cerclage (5.8%), weight gain above 14 kg (9.8%), preterm labour (8.4%), delivery at > or = 42 weeks (3.1%), premature rupture of the membranes (16.4%), meconium-stained amniotic fluid (14.4%), and up to 6-hour duration of labour (73.2%, elective caesarean section (6.8%), emergency caesarean section (5.7%), vacuum extraction (3.8%) and placental lysis or uterine exploration (3.8%) were more common in women > or = 35 years of age (P < 0.05). Higher rates for 7-to-12-hour duration of labour (33.6%) and episiotomy (64.2%) were found in the control group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503237 TI - [Current status of occiput posterior labor presentation]. AB - Nowadays reports about mechanical problems in obstetrics are rare. Report about the occipito-posterior position. It may be possible that these increasing anomalies. The reason for this fetal acceleration are and changes in pelvic anatomy. PMID- 8503238 TI - [Adolf Gusserow (1836-1906), founding of the 2d University Gynecologic Clinic of the Charite and the Berlin Society of Obstetrics and Gynecology. IV]. AB - Adolf Gusserow was one of the outstanding German gynecologists at the end of the XIX. century. Although interested in the entire discipline of obstetrics and gynecology including related areas, he is merely unknown today. This paper describes the biography of Prof. A. Gusserow, but also his importance for the Berlin Society of Obstetrics and Gynecology. PMID- 8503239 TI - [Who invented the episiotomy? On the history of the episiotomy]. AB - The most frequent operation in obstetrics is to cut ans suture an episiotomy. This technique was first mentioned in 18th century. Yet is took 100 years to be commonly accepted after it was first publicated 1810 in a medical journal. This paper will show the historical development of an episiotomy that nowadays still is a topic contrary discussion. PMID- 8503240 TI - Testicular relapse in Philadelphia chromosome positive acute lymphoblastic leukaemia. AB - A case of Philadelphia-positive (Ph) acute lymphoblastic leukaemia (ALL) in a 40 year-old male is presented. At diagnosis, 80% of bone marrow cells were Ph. Remission with normal blood counts was achieved but the marrow became hypercellular, indicating conversion to chronic granulocytic leukaemia (GCL). The Ph clone persisted with a variable percentage of Ph cells. He developed testicular relapse 38 months from diagnosis. The patient died when engraftment with a matched unrelated bone marrow transplant failed. Molecular investigation of DNA prepared from diagnostic and remission bone marrow and from testicular tissue in relapse revealed the same sized rearranged fragment of the BCR gene using a probe to the major breakpoint cluster region. This case confirms that testicular involvement due to infiltration of the testes by the original Ph leukaemic clone may occur as an unusual complication in Ph ALL. Conversion to chronic-phase GCL, a rare occurrence in Ph ALL, may have contributed to the unusually long survival. PMID- 8503241 TI - Ectopic medullary hematopoiesis as a cause of ascites in agnogenic myeloid metaplasia. Case report and review of the literature. AB - We report an unusual case of a 44-year-old female patient with 'malignant' ascites caused by ectopic foci of extramedullary hematopoiesis in the course of agnogenic myeloid metaplasia. The patient had suffered also from severe Coombs positive acquired hemolytic anemia and had been splenectomized. Two years after splenectomy, ascites caused by peritoneal implants of hematopoietic tissue appeared. The ascites responded promptly to treatment with busulfan and hydroxyurea. The clinical picture, treatment and a review of the literature concerning the mechanisms of this uncommon evolution are discussed. PMID- 8503242 TI - Minimal residual disease detected by the PCR in chronic myeloid leukemia. Comparison of cyclophosphamide-total body irradiation and busulphan cyclophosphamide bone marrow transplantation conditioning. PMID- 8503243 TI - Interpretation of the AgNOR pattern in hematologic cytology. PMID- 8503244 TI - Iron chelators may enhance erythropoiesis by increasing iron delivery to haematopoietic tissue and erythropoietin response in iron-loading anaemia. AB - Based on the mode of action of iron chelators, one might expect a decrease in bone marrow iron availability, resulting in worsening of the anaemia in certain types of iron-loading anaemia. However, improvement of anaemia or reduction in transfusion requirements during chelation treatment has been reported in various types of iron-loading anaemia. It is suggested that iron chelators act as mediators facilitating iron release from storage sites and its delivery to haematopoietic tissues. In addition, a reduction of iron stores may upregulate erythropoietin response and bring about a decrease of disease activity in inflammatory disorders, resulting in a haemoglobin rise. Large trials with (oral) iron chelators are required to verify these possible effects. PMID- 8503245 TI - Effect of vincristine, adriamycin and glucocorticoids on myeloma cells in vitro. AB - The effect of in vitro exposure to vincristine, Adriamycin, and glucocorticoids was studied in 4 human myeloma cell lines. The drug concentrations tested approximated the steady-state plasma level achievable clinically. Marked growth inhibition was seen in all 4 cell lines with vincristine, but in only 2 with Adriamycin. Glucocorticoids were only minimally inhibitory. The inhibition by glucocorticoids was reversible after drug removal, but that by vincristine and Adriamycin was sustained except the vincristine inhibition of ARH-77 cells. The degree of cell growth inhibition paralleled the reduction in tumor cell 3H thymidine uptake. Cell cycle distribution analysis showed an arrest of myeloma cells at M/G2 phase by vincristine and Adriamycin and an inhibition of myeloma cells from entering into S phase by dexamethasone. Dose-response analysis with ARH-77 cells, a cell line that appeared the most chemoresistant, showed that the growth-inhibitory effect of Adriamycin and vincristine was roughly proportional to the product of drug concentration and exposure time. However, in contrast to Adriamycin, an effective vincristine concentration and exposure time that totally inhibited cell growth was unable to prevent cell regrowth after drug removal. A higher vincristine concentration appeared to be more effective in preventing cell regrowth. PMID- 8503246 TI - Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy induced granulocytopenia in patients with malignancies. AB - To investigate the effect of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on cytotoxic chemotherapy-induced granulocytopenia, we performed an open nonrandomized clinical trial in 46 patients with malignancies receiving cytotoxic chemotherapy regimen. Twenty-six patients who received two cycles of the identical chemotherapy regimen and had granulocytopenia less than 1 x 10(9) cells/l after the first cycle of chemotherapy were eligible for this study. They received 60, 125 or 250 micrograms/m2/day of rhGM-CSF randomly. The nadirs of peripheral granulocytes demonstrated significantly much higher levels in all dosages studied than those of control cycles. The duration of granulocytopenia was shortened with rhGM-CSF support. Such granulocyte recovery appeared in parallel with increasing dosages of GM-CSF, thus, infections with febrile episodes were reduced. Toxicity of rhGM CSF was generally well tolerated. PMID- 8503247 TI - Quantitation of immune-mediated erythrophagocytosis and rosetting in developing macrophages. AB - As part of our ongoing investigations of mononuclear phagocytes in health and disease, measurement of antibody-dependent erythrophagocytosis and rosette formation was carried out during human macrophage development in a suspension culture system. Cells derived from 12 normal human subjects were studied at the monocyte (day 0) and macrophage (day 6) stage of development. Analysis of variance demonstrated significant differences between monocytes and macrophages: the mean proportions of cells (+/- SEM) showing erythrophagocytosis were 0.09 (+/ 0.02) and 0.24 (+/- 0.06), respectively, and the average numbers of engulfed red cells (+/- SEM) were 1.12 (+/- 0.02) and 1.38 (+/- 0.11), respectively. No significant difference was detected in rosette formation. It is concluded that (1) immune-mediated activity of developing macrophages can be quantitated; (2) functional changes take place over 6 days of culture; (3) macrophages show more erythrophagocytic activity than monocytes, and (4) the method should be of value in making quantitative comparisons of their functional development in haematological and other disease states. PMID- 8503248 TI - Rapid detection of Chinese G gamma+(A gamma delta beta)zero-thalassemia by polymerase chain reaction. AB - The Chinese G gamma+(A gamma delta beta)zero-thalassemia is caused by a deletion of more than 80 kilobases. It has a beta(+)-thalassemia phenotype and should be differentiated from other mutations causing beta-thalassemia. Using polymerase chain reaction with three oligonucleotide primers bridging the breakpoints, the deletion can be detected easily. The method is useful in the genetic counseling and prenatal diagnosis of the at-risk families. PMID- 8503249 TI - Neutropenia associated with myelofibrosis in systemic lupus erythematosus. AB - Although myelofibrosis has been described in systemic lupus erythematosus (SLE), this coexistence must be rare since there are few reports showing this combination. The possible relationship between hematologic abnormalities and SLE remains unresolved. The authors describe a 39-year-old woman with persistent neutropenia and SLE in whom myelofibrosis was found. Unlike previously reported cases, myelofibrosis did not resolve with steroid therapy. In this report, the clinical course of the patient is compared with others described in the literature. PMID- 8503250 TI - Agranulocytosis in a patient with thalassaemia major during treatment with the oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one. AB - Agranulocytosis developed in a 20-year-old Greek patient with beta-thalassaemia major, 11 weeks after commencing chelation with the oral iron chelator 1,2 dimethyl-3-hydroxypyrid-4-one (L1) and 6 weeks after receiving the drug at a total daily dose of 105 mg/kg. The patient presented with generalised weakness, low-grade fever and sore throat. The total white cell count was 2.0 x 10(9)/l with 0.1 x 10(9)/l neutrophils. The patient was admitted to hospital and successfully treated with intravenous broad-spectrum antibiotics. Neutrophil count recovered 7 weeks later. A number of immunological tests were performed in an attempt to elucidate the cause of agranulocytosis. These investigations gave inconclusive evidence for the presence of a weak IgM antibody to myeloid cells exposed to L1 in this patient. Further studies are required, however, to evaluate the mechanism in any other patient who develops agranulocytosis in association with L1 therapy. PMID- 8503251 TI - Sustained remission of idiopathic hypereosinophilic syndrome following alpha interferon therapy. AB - Two patients with idiopathic hypereosinophilic syndrome (HES) refractory to treatment with corticosteroids and hydroxyurea received alpha-interferon (alpha IFN) for 3 and 1 years, respectively. Eosinophil counts dropped below 1.5 x 10(9)/l at weekly doses of 2-7 x 3 million units alpha-IFN. More than a year after discontinuation of alpha-IFN, 1 patient remains in a stable remission. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plasma levels were found to be normal in this patient, although GM-CSF is known to stimulate eosinophil proliferation in vitro. Based on the favorable clinical results of alpha-IFN, further studies are necessary to define its role in the treatment of HES. PMID- 8503252 TI - Hypothesis: the bradyphrenia of parkinsonism is a nosological entity. AB - Reaction time was studied in 103 subjects with idiopathic parkinsonism and 144 without. Central processing time, as measured by the response to a warning, had a component which could be explained by the presence or absence of parkinsonism, but not by the ageing process, a mental test score, or consumption of exogenous substances. Depression did not influence the efficiency of response. Cigarette smoking and anti-parkinsonian medication were associated with greater efficiency. PMID- 8503253 TI - Assessment of the bradyphrenia of parkinsonism: a novel use of delayed auditory feedback. AB - Sufferers from parkinsonism have difficulty shifting or developing an appropriate mental set. Delayed auditory feedback may, therefore, disrupt their speech more than that of healthy controls. This was the case when 104 subjects with idiopathic parkinsonism and 144 without were compared. Moreover, the disruptive effect was complementary, in discriminating between those with and without clinical parkinsonism, to the response in reaction time to a warning. Unlike the latter, the disruption caused by delayed auditory feedback appeared independent of mental test score results and uninfluenced by consumption of tobacco or anti parkinsonian therapy. Neither were influenced by a rating of affect. More precise delineation of the mental disorders of parkinsonism is needed in clinical practice, set against background information on prognosis and drug responsiveness. PMID- 8503254 TI - SPET imaging of cerebral perfusion in patients with non-refractory temporal lobe epilepsy. AB - The pattern of regional cerebral blood flow was assessed by single photon emission tomography and (99mTc)HM-PAO in 28 patients with clinical diagnosis of non-refractory cryptogenic temporal lobe epilepsy on chronic treatment with carbamazepine. Each patient underwent a magnetic resonance imaging study of the brain. An EEG was performed concurrently with the assessment of cerebral blood flow. Areas of focal hypoperfusion were observed in 8/28 patients, and a concurrent EEG focus was identified in 10/28 patients. Areas of hypoperfusion and the EEG foci were consistent in 6 of the 10 patients with EEG abnormalities; in 2 patients hypoperfusion and the EEG abnormalities were on opposite sides, though in homologous areas; in 2 patients the perfusion pattern was normal in spite of the EEG abnormalities. The number of clinical seizures and EEG abnormalities was higher for the patients presenting with cerebral hypoperfusion than for those with normal perfusion. It is concluded that the evaluation of cerebral blood flow may provide useful information for both diagnostic and prognostic assessment of these patients. PMID- 8503255 TI - Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions: crossed cerebral diaschisis. AB - Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using 99mTc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduction (average 10%) in contralateral hemispheric cortex. In all four cases clinical signs of unilateral cerebellar dysfunction were still present when rescanned 1 to 4 months later and the relative CBF decrease in the contralateral cortex of the forebrain also remained. The basal ganglia contralateral to the cerebellar lesion CBF showed variable alterations. A relative CBF decrease was seen in upper part of basal ganglia in all four cases, but it was not a constant phenomenon. A relative CBF increase in both early and late SPECT scans was seen at low levels of neostriatum in two cases. The remote CBF changes in cerebellar stroke seen in the forebrain are probably caused by reduced or abolished cerebellar output. The term "Crossed Cerebral Diaschisis" may be used to describe these CBF changes that would appear to reflect both decreased and increased neuronal activity. PMID- 8503256 TI - Cytokine production by peripheral blood monocytes/macrophages in multiple sclerosis patients. AB - To determine the function of monocytes/macrophages in the acute phase of multiple sclerosis (MS), we investigated the production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta and IL-6 by peripheral blood monocytes/macrophages (PBM) in patients with MS, other autoimmune neurological disease (OAND), other neurological disease (OND) and normal controls was assessed using enzyme-linked immunosorbent assay (ELISA). When stimulated with lipopolysaccharide or phorbol ester, PBM obtained during acute phase of MS relapse patients produced significantly higher amounts of all these cytokines than did PBM from patients with chronic stable MS or OAND or OND or from normal controls. The results suggest a possible role of activated monocytes/macrophages in the acute exacerbation of MS. PMID- 8503257 TI - Relationship between vascular factors and white matter low attenuation of the brain. AB - To study the relationship between vascular factors and white matter low attenuation of the brain (WMLA), computer tomography findings of 251 patients were re-interpreted. Clinical data on patients were collected from the hospital records. It was possible to obtain sufficient clinical data on 204 patients who were included in the study. WMLA changes, on computer tomography, were found in 51.5% of patients. WMLA was most commonly present in patients with vascular (69.8%) and combined (69.2%) dementia. The occurrence of WMLA did not differ between patients with Alzheimer's disease (26.7%) and those without dementia (35.9%). Arterial hypertension, coronary heart disease, or diabetes were not associated with WMLA. Heart failure and orthostatic hypotension, were found to be more commonly present in patients with than in those without WMLA (34.0% vs 14.3%, p = 0.0012; 10.0% vs 2.0%, p = 0.036). Both systolic and diastolic low blood pressure values were associated with WMLA unlike hypertensive blood pressure values. Atrial fibrillation in electrocardiography was associated with WMLA, while neither left ventricular hypertrophy nor myocardial infarction was. When several explanatory variables were adjusted by logistic regression analysis, age, heart failure, and systolic blood pressure below 130 predicted WMLA. In conclusion, the association between WMLA and vascular factors with hemodynamic significance suggests that cerebral hypoperfusion may contribute to the genesis of WMLA. PMID- 8503258 TI - Adamantiadis-Behcet's syndrome: central nervous system involvement. AB - The prevalence of CNS involvement of Adamantiadis-Behcet's syndrome (A-Bs) vary widely. Long-term follow-up studies of CNS involvement have rarely been reported. Five patients with CNS involvement, who were followed up from 2 to 9 years, are presented. Clinicolaboratory investigations (cerebrospinal fluid examination, electroencephalogram, brain CAT scan and MRI) were carried out. One patient had four and two patients had two attacks of CNS involvement with various clinical manifestations. The other two patients had a rather chronic course with a single slight CNS attack. Raised proteins and IgG were found in the CSF. Abnormal electroencephalographic findings were detected in three patients. Communicating hydrocephalus and various other abnormalities on CT scan and MRI were noted. All patients received corticosteroids and immunosuppressants during the attack period. PMID- 8503259 TI - Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease. AB - Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified. PMID- 8503260 TI - Alzheimer's disease compared with cerebrovascular dementia. Neuropsychological similarities and differences. AB - Forty-eight patients with a clinical diagnosis of Alzheimer's disease, 30 patients with cerebrovascular dementia, and 48 normal controls were assessed with a battery of neuropsychological tests designed to measure the following cognitive processes: orientation to time and place, memory, visual-perceptual and constructional skills, language, conceptualization, attention, and executive functions (planning, self-regulation and fine motor coordination). The differences detected were in orientation to time and place, in immediate and delayed recall of a short story, and in naming in which the patients with Alzheimer's disease were significantly disadvantaged. Vice versa, in attention processes, self-regulation, planning, and fine motor coordination tasks the patients with cerebrovascular dementia were more severely impaired; these disturbances resemble some of those occurring in frontal lobe syndromes. PMID- 8503261 TI - Biogenic amine metabolites in the CSF of patients with late onset and alcoholic ataxias. AB - The levels of monoamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5 hydroxyindoleacetic acid (5-HIAA) were measured in lumbar cerebrospinal fluid (CSF) from 10 patients with late onset ataxia, 8 patients with alcoholic ataxia and 18 control patients. The levels did not differ significantly among the three groups of patients suggesting that the central neuronal systems utilizing dopamine, noradrenaline and 5-hydroxytryptamine do not have a significant pathophysiological role in these forms of ataxias. The measurement of CSF amine metabolites probably does not contribute to the differential diagnosis of ataxias. PMID- 8503262 TI - Accuracy of the Mini-Mental Status Examination as a screening test for dementia in a Swedish elderly population. AB - The aim of this study was to determine the accuracy of the Mini-Mental Status Examination (MMSE) as a screening test for dementia in an elderly Swedish population. All the inhabitants over 74 years of age in one area of Stockholm took the MMSE. The test was then compared to the clinical diagnosis of dementia. With a cut-off point of 23/24, the MMSE had a sensitivity of 87%, specificity of 92%, and positive predictive value (PPV) of 69%. Age, sex, and education did not substantially affect the specificity and the PPV, but had a slight effect on the sensitivity. The main causes of the false positives were somatic and psychiatric disorders. These results are in agreement with studies performed with similar methods and comparable populations. PMID- 8503263 TI - Immunohistochemical findings in vasculitic neuropathies. AB - Fifteen sural nerve biopsies of vasculitic neuropathies have been compared with 11 cases of different non-vasculitic neuropathies and normal nerves from brain dead organ donors. The APAAP (alkaline phosphatase monoclonal anti-alkaline phosphatase) immunostaining method was applied to cryostat sections from unfixed snap-frozen tissue samples. Immunoglobulins IgG, IgM, IgA, complement factors and light chains were reactive in biopsies of normal nerves as well as of vasculitic and nonvasculitic neuropathies. A strong reaction against IgE in the epineurial vessel walls was only seen in cases of Churg-Strauss-vasculitis. Antibodies against MHC class II (HLA DR) were positive in most of vasculitic infiltrates. Vascular endothelial cells were positive with anti MHC class I in all biopsies. A typical finding in all vasculitic neuropathies was the infiltration of epineurial vessels with CD4 positive and, to a lesser extent, CD8 positive lymphocytes. CD22 positive lymphocytes (B cells) have only been seen in about one third of vasculitic neuropathies. CD16 positive cells (NK-cells or neutrophils) could be demonstrated only in two biopsies. CD68 positive cells (macrophages) are frequently seen in most cases of neuropathy regardless of their etiology. The results support the concept of a primary T-cell mediated process against epineurial vessels as the most important mechanism in the pathogenesis of vasculitic neuropathies. In some cases with small epineurial infiltrates the vasculitic process can only be recognized with antibodies against CD4 or CD8. Therefore, the immunohistochemical evaluation of sural nerve biopsies may be helpful for identifying cases with microvasculitis. PMID- 8503264 TI - Topical naphazoline in treatment of myopathic ptosis. AB - We instilled naphazoline Hcl (0.1%), an imidazole derivative with preferential alpha-2 activity, in 17 eyes of 12 patients with myopathic ptosis due to involvement of the levator palpebrae superioris, in the attempt to selectively stimulate Muller's smooth muscle. Naphazoline significantly widened the palpebral fissure with little change in pupillary diameter and no significant change in ocular pressure, visual acuity and near point determination. However, a reduction of the effect, probably due to tachyphylaxis, was noticed when using naphazoline regularly several times a day for few weeks. In conclusion naphazoline has powerful cosmetical and functional effects in mild to moderate myopathic ptosis above all if taken occasionally. PMID- 8503265 TI - Increased type III/I collagen and alpha 1(I)/alpha 2(I) chain in a bronchopulmonary dysplastic lung. AB - The type ratio of collagen III/I and molecule ratio of alpha 1(I)/alpha 2(I) were analysed in lungs from five infants with bronchopulmonary dysplasia (BPD) and seven control infants. All five BPD lungs showed typical characteristics, with pulmonary fibrosis and irregular cystic formation at postmortem examination. A pepsin digestion technique followed by interrupted gel electrophoresis was performed for the determination and molecular analysis of collagens III and I. The ratio of collagen types III and I were significantly increased in BPD lung (P < 0.005). The ratio of alpha 1(I) and alpha 2(I) were also significantly increased in BPD lung (P < 0.05). It is likely that collagen III is predominantly increased and that the alpha 1(I) trimer is formed in the active stage of BPD lungs. PMID- 8503266 TI - Serum thyroid hormones and pituitary response to thyrotropin-releasing hormone in epileptic children receiving anti-epileptic medication. AB - Thyroid hormones and pituitary function were assessed in 49 children with epilepsy who were receiving either a single medication of carbamazepine, phenobarbital and valproate or a combination of carbamazepine with phenobarbital or valproate. All therapeutic regimens except valproate monotherapy were associated with low levels of circulating thyroxine, free tri-iodothyronine and free thyroxine. Carbamazepine with valproate was associated with the lowest serum concentration of thyroid hormones. It seems probable that accelerated hormone metabolism is responsible for these hormonal changes. However, all drug regimens also had effects on the function of the hypothalamic pituitary axis. Because of these findings, thyroid hormones should be checked frequently during anti epileptic drug treatment, although clinical hypothyroidism was not seen in our patients. PMID- 8503267 TI - Normal levels of IgG subclass in childhood determined by a sensitive ELISA. AB - Normal values of all IgG subclasses were determined using a sensitive ELISA in children aged from newborn to 14 years. The upper and lower limits of normal values of all IgG subclasses were obtained in all the age groups using 29 umbilical cord blood samples from full-term newborns and 308 venous blood samples from normal infants and children. The trends in the levels of IgG1, IgG2 and IgG3 with age were almost similar to previous reports. IgG4 levels decreased gradually until reaching the lowest level at 7 to 12 months and increased gradually with age, reaching a plateau at 12 to 14 years of age. Thus, the lower limit of serum IgG4 levels was determined using our method. PMID- 8503268 TI - Serum anti-streptococcal IgA, IgG and IgM antibodies in IgA-associated diseases. AB - Serum anti-streptolysin-O antibody (ASO) and anti-streptococcal polysaccharide antibody (ASP) of IgA, IgG and IgM classes were measured using an enzyme-linked immunosorbent assay in 41 children with IgA nephropathy (Group A), 15 children with uncomplicated anaphylactoid purpura (Group B) and 13 children with purpura nephritis (Group C). The serum concentrations of the IgA, IgG and IgM classes were measured by single radial immunodiffusion. When compared with sex- and age matched controls, the concentrations of serum IgA (but not of IgG or IgM) were significantly increased in the three groups studied. The titers of ASO of the IgA and IgM classes, and those of ASP of the IgA and IgG classes, were significantly increased in Group A. In Group B, only the ASP titers of the IgA class were significantly increased. No significant difference was noted in the titers of either ASO or ASP of any class in Group C. Thus, increased antibody response in IgA nephropathy is not restricted to IgA. Anaphylactoid purpura with or without renal disease appears to be different in its humoral anti-streptococcal response from IgA nephropathy. PMID- 8503269 TI - A longitudinal study of blood pressure, cholesterol and left ventricular muscle volume in children: the Shimane Heart Study. AB - Three hundred and forty-four healthy schoolchildren living in Izumo City, Shimane Prefecture, Japan, were assessed at 3 year intervals from 6 to 15 years, starting in 1978 (Cohort 1) or 1981 (Cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y - z)/N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1, there is positive tracking. For systolic blood pressure (SBP) measurements (except at 6 years old) and serum cholesterol levels, all Ti were greater than 1.0 regardless of the time when tracking was commenced. Tracking indices were slightly greater in the serum cholesterol levels than in the SBP measurements. Left ventricular muscle volume indices (LVMVI) were calculated by echocardiographic measurements. In girls, the LVMVI was larger only in the above median SBP group at the age of 12 years (P < 0.01), but the LVMVI of the higher SBP (above median) group was larger than in the lower (below median) group at every age in boys; the difference was statistically significant (P < 0.05) at 12 and 15 years of age. Left ventricular mass enlargement may occur in the prehypertensive stage in humans as well as in rats. PMID- 8503270 TI - A study of the hemoglobin levels in breast-fed infants in one village of Okinawa prefecture. AB - We investigated the prevalence of anemia and the hemoglobin levels in breast-fed infants. Three hundred and fifty-six healthy children with different feeding methods were studied longitudinally. The results showed that the prevalence of anemia was higher and the hemoglobin levels were lower in breast-fed infants compared with those in partially breast-fed or formula-fed infants at late infancy. PMID- 8503271 TI - A case of congenital herpes zoster. AB - A 5 day old girl was transferred to the pediatric ward of Kyushu University Hospital because of papules noted since birth. The papules were distributed on her skin corresponding to the dermatomes innervated by the left Th1-Th3 and the left L1-L3. Varicella-zoster virus antigens were detected in scrapings of incised papules. The diagnosis of herpes zoster was made and acyclovir (ACV) was administered. She responded to ACV well, but she experienced a recurrence twice after discontinuation of ACV. This is the first report of 'congenital herpes zoster', which supports the hypothesis that varicella embryopathy is the sequelae of herpes zoster in utero. PMID- 8503272 TI - Moebius syndrome associated with pituitary dwarfism and hypoplastic optic disc. AB - A 17 year old male patient with Moebius syndrome with pituitary dwarfism and unilateral hypoplastic optic disc is presented. Although there have been several reports of an association of Moebius syndrome and pituitary dysfunction, growth hormone deficiency has not been reported previously. These associations may give some insight into the pathogenesis of Moebius syndrome. PMID- 8503273 TI - Hypofibrinogenemia in a girl with Langerhans cell histiocytosis during etoposide and prednisolone therapy. AB - A case of a girl with Langerhans cell histiocytosis who had hypofibrinogenemia during etoposide (VP-16) and prednisolone therapy is described. A patient on a three times per week schedule of 100 mg/m2 etoposide in combination with 40 mg/m2 of prednisolone every day had hypofibrinogenemia of 90 mg/dL after 12 doses of etoposide. Hypofibrinogenemia improved after discontinuing the course of etoposide. The clinical course suggested that the combination of etoposide with prednisolone caused this side-effect. Although the exact mechanism of toxicity of etoposide with prednisolone remains unknown, it is possible that the side-effect might be due to reduced production of fibrinogen in the liver. Careful monitoring of fibrinogen is mandatory in patients receiving etoposide and prednisolone. PMID- 8503274 TI - Bile duct atresia following extended right hepatectomy because of a tumor. AB - A 19 month old male infant with a mesenchymal hamartoma of the liver underwent an extended right hepatectomy. Serum bilirubin gradually rose until 3 months after the surgery, and obstructive jaundice and acholic stools were manifested at 6 months. Percutaneous transhepatic cholangio-drainage was performed. Cholangiography showed dilation of the intrahepatic bile duct of the residual lateral segment and complete obstruction of the extrahepatic bile duct. A second operation for reconstruction of the biliary tract was performed 10 months after the first surgery. No aspect of an extrahepatic biliary tract was found. Histological inspection of a surgical specimen of remnant tissue revealed only cicatricial connective tissue without any biliary structures. The clinical course has been uneventful for 18 months since the second surgery. The cause of bile duct atresia in this case is strongly suggested to be an ischemic change due to devascularization of the extrahepatic biliary tract following hepatic resection because of a tumor. To prevent this kind of complication, hepatico-enterostomy should be performed close to the cut surface of the liver. PMID- 8503275 TI - A case of biliary stricture caused by cavernous transformation of the portal vein. AB - A case is reported of extrahepatic obstruction of the portal vein with the unusual complication of obstructive jaundice that resulted from compression of the common bile duct caused by cavernous transformation of the varicose network. It is surgically impossible to repair choledochal stenosis resulting from enlarged varices in the vicinity of the common bile duct. In this case, internal drainage from the biliary duct to the duodenum using a silastic tube and a reservoir implanted in the subcutaneous space successfully eliminated the jaundice. PMID- 8503276 TI - Children as urban citizens in the nurturing environment of the city. PMID- 8503278 TI - Granulocyte elastase alpha 1-proteinase inhibitor complex measurement in very low birthweight infants with severe intraventricular hemorrhage. AB - We investigated the relationship between the levels of granulocyte elastase alpha 1-proteinase inhibitor complex (E-alpha 1-PI) in plasma and severe intraventricular hemorrhage (IVH) in very low birthweight infants. The concentrations of E-alpha 1-PI and the ratio of the concentrations of E-alpha 1 PI to polymorphonuclear leucocyte counts within 24 h of birth in infants with severe IVH were significantly higher compared with those in infants without severe IVH. E-alpha 1-PI seems to be a useful indicator of IVH. PMID- 8503277 TI - Polymerase chain reaction for diagnosis of infectious diseases. AB - The polymerase chain reaction (PCR) has been utilized and demonstrated to be useful for detecting minute amounts of a wide variety of infectious agents. In such studies, one must keep in mind that the most appropriate conditions for amplification vary with organisms of interest. In this study, PCR was used as a rapid and sensitive method for detecting infectious agents for which three assay systems were devised comprising the method for the amplification of human T cell leukemia virus type I, Mycobacterium tuberculosis and Mycoplasma pneumoniae. The possibility of vertical transmission of human T cell leukemia virus type I through cord blood was demonstrated using cord blood mononuclear cells from carrier mothers of this virus. In the study of Mycobacterium tuberculosis, PCR was shown to be efficient, particularly in detecting this organism in extrapulmonary cases. Evidence of direct invasion into the central nervous system by Mycoplasma pneumoniae and the concomitant occurrence of mycoplasmaemia in the mycoplasmal central nervous system involvement was obtained using PCR. These results validated the potential of PCR in the clinical research of infectious diseases. PMID- 8503279 TI - Inhibition of crystallins-induced inflammation in rabbit eyes with five phytogenic compounds. AB - Ocular inflammation was induced by injection of crystallins (lens protein) intracamerally and endotoxin intravitreously into rabbit and rat eyes, respectively, and was measured with fluorophotometry by quantitating the amount of fluorescein which entered into the globe. Five compounds isolated from anti inflammatory Chinese herbs were studied for their effects on ocular inflammation. It was found that lens protein-induced inflammation was inhibited significantly by the topical instillation of pulegone (0.5%), friedelin (0.5%), and sabinene (1%), but not by dihydrojasmon or naringin at concentrations up to 1%. However, none of these compounds inhibited endotoxin-induced posterior uveitis. PMID- 8503280 TI - Effects of menadione on 1,2-dimethylhydrazine-induced mouse colon adenocarcinoma. AB - The effects of menadione (Vit K3) administered at 20 or 40 mg.kg-1 ig 3 times a week for both 24 and 28 wk on 1,2-dimethylhydrazine (DMH)-induced mouse colon adenocarcinomas were investigated. At the 24th wk, the number of colon tumors in Vit K3 20 or 40 mg.kg-1 group (0.3 +/- 0.5 and 0.5 +/- 0.8, respectively) was less than that of DMH controls (2.1 +/- 2.5, P < 0.05), but the difference in incidence of colon tumors in these 3 groups was not significant (P > 0.05). After 28 wk, the tumor incidence of both Vit K3 groups (each 8 of 13) was lower than that of DMH controls (13 of 13, P < 0.05); the number of colon tumors of Vit K3 40 mg.kg-1 group (1.3 +/- 1.3, P < 0.05) was decreased, whereas the Vit K3 20 mg.kg-1 group (3.0 +/- 5.1, P > 0.05) was not different from the DMH controls (7.3 +/- 9.3). Determination of the nuclear DNA content of cells from DMH-induced mouse colon mucosa (24 wk) indicated that Vit K3 20 or 40 mg.kg-1 group showed lower DNA content (1.92 +/- 0.12 C and 1.91 +/- 0.10 C, respectively) decreased values of percent-over-3C and -4C and narrow distribution range. Besides, the colon mucosa of DMH-treated mice (28 wk) showed higher superoxide dismutase (SOD) activity (70 +/- 28 U/mg protein, P < 0.05) than the normal controls (30 +/- 20 U/mg protein). Vit K3 40 mg.kg-1 reduced the elevated SOD activity markedly (44 +/- 23 U/mg protein, P < 0.05). PMID- 8503281 TI - Cyclopiazonic acid causes endothelium-dependent relaxation in rat aorta. AB - The effects of cyclopiazonic acid (CPA), a selective inhibitor of Ca(2+)-pump ATPase for endoplasmic reticulum (ER), on the contractility of rat aorta with and without intact endothelium were studied to investigate the possible involvement of endothelial ER Ca(2+)-pump in the release of endothelium-derived relaxing factor (EDRF), which is known to cause vascular relaxation or inhibition of phenylephrine (PE)-precontracted aorta. When added to the organ bath cumulatively, CPA concentration-dependently caused gradual development of contraction, which was much less in aortic rings with intact endothelium than in endothelium-denuded aortic rings. But CPA at low concentrations (1-3 mumol.L-1) induced vascular relaxation when added to PE (3 mumol.L-1)-precontracted aortic rings with intact endothelium, but not in denuded aortic rings. This relaxant effect of CPA is very similar to the effect of acetylcholine (ACh), which is well recognized to be mediated by the release of EDRF from the endothelium. NG-nitro-L arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, completely prevented the vascular relaxation induced by CPA or ACh and the inhibitory effect of L-NAME was partially reversed by L-arginine (L-Arg). Treatment of the aortic rings with nifedipine (Nif) 0.3 mumol.L-1 did not affect the relaxant effect of ACh or CPA on PE-induced contraction indicating that the Ca(2+)-entry to the endothelial cells as a result of receptor activation by ACh or ER Ca(2+)-pump inhibition by CPA was via channels other than L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503282 TI - Platelet activating factor production in bovine cerebral microvascular endothelial cells and its drug inhibition. AB - The production of platelet activating factor (PAF) in bovine cerebral microvascular endothelial cells (CME cells) and the effects of tetrandrine (Tet) and dauricine (Dau) on the PAF production were investigated. PAF was determined by the aggregation of washed rabbit platelets. The results showed that the CME cells produced PAF 5.93 ng/8.5x 10(5) cells under the calcimycin 2.5 mumol.L-1 stimulation. Tet and Dau 1, 10, and 100 mumol.L-1 inhibited the production of PAF by 18.2%, 51.8%, 56.8%, and 26.3%, 63.3%, 65.9%, respectively. Tet concentration dependently inhibited the PAF 9.1 nmol.L-1 induced washed rabbit platelets aggregation with the IC50 of 3.05 mumol.L-1 (95% confidence limits: 0.59-15.86 mumol.L-1). The binding of [3H]triazolodiazepine to the CME cells was partially displaced by Tet 0.02-33.00 mumol.L-1. It is suggested that the cerebrovascular system produces PAF at the pathological conditions and the inhibition of Tet and Dau. PMID- 8503283 TI - Cardiac responses induced by bradykinin activation of canine ganglial plexus between aorta and pulmonary artery. AB - To study the function of bradykinin-sensitive cardiac neurons, bradykinin (50 micrograms) was injected into the ganglial plexus between aorta and pulmonary artery (A-PGP) in 33 anesthetized open-chest dogs. Either positive or negative inotropic and chronotropic responses were elicited. Control injections of 0.1 ml saline into A-PGP and injections of bradykinin (50 or 100 micrograms) into the right marginal ganglial plexus did not elicit any cardiac response. After acute decentralization, bradykinin (50 micrograms) was again injected into the same locus of A-PGP. Some positive responses were still induced, while negative ones were completely abolished. These data suggested that bradykinin can directly activate the efferent neurons associated with sympathomimetic activation, and indirectly activate them by stimulation of afferent neurons. PMID- 8503284 TI - [3,4-Diaminopyridine-evoked norepinephrine release and B-50 (GAP-43) phosphorylation]. AB - 3,4-Diaminopyridine (3,4-DAP 100 mumol.L-1) evoked [3H]norepinephrine ([3H]NE) release in rat hippocampal slices preincubated with [3H]NE and superfused with medium with or without Ca2+. Phorbolester 4 beta-phorbol 12, 13, dibutyrate 1 mumol.L-1) enhanced and polymyxin B (100 mumol.L-1) inhibited the release of [3H]NE under both conditions. The neuron-specific protein B-50 is a major presynaptic substrate of protein kinase C and involved in exocytosis. Using in situ protein phosphorylation analyzed by SDS-PAGE and autoradiography, we observed that B-50 phosphorylation was significantly decreased by 3,4-DAP in the presence of extracellular Ca2+ and completely inhibited by removal of extracellular Ca2+. It was suggested that B-50 phosphorylation was not involved in 3,4-DAP-evoked [3H]NE release. PMID- 8503285 TI - [Phencyclidine receptors in porcine coronary artery]. AB - By using radioligand assay, there was a phencyclidine (Phe) binding site in porcine coronary artery. This binding was specific, reversible, saturable, and stereoselective. The Scatchard analysis showed that the binding site was a single class, with dissociation constant (Kd) and maximum binding (Bmax) of 27.7 +/- 6.9 nmol.L-1 and 0.82 +/- 0.15 pmol/mg protein, respectively. The displacement experiments revealed that the [3H]Phe binding was displaced by nonradioactive Phe, TCP (Phe receptor agonists), and dextrophan (its antagonist). d-INN, a ligand of sigma receptor, had a weaker activity of displacement. These showed a dose-dependent manner. Both etorphine, an agonist of opioid receptor, and N methyl-D-aspartic acid (NMDA), an excitatory amino acid, failed to displace the binding. These results suggest that the Phe receptors exist in the porcine coronary artery. PMID- 8503286 TI - [Effects of mebendazole on glucose, glycogen, lactic acid, and lactate dehydrogenase in Echinococcus granulosus cyst wall]. AB - The glucose, glycogen, and lactic acid contents in Echinococcus granulosus cyst wall were 3570 +/- 623, 1276 +/- 126, and 267 +/- 29 micrograms.g-1, respectively. The lactate dehydrogenase (LDH) activity in the cyst wall was 4307 +/- 297 U/(min.mg protein). When infected mice were treated ig with mebendazole (Meb) 25 or 50 mg.kg-1.d-1 for 7-14 d, the glucose and glycogen contents in the cyst wall decreased markedly. No apparent changes in lactic acid and LDH activity were seen. The results suggested that Meb had no effect on glycolysis of the cyst wall, but it exhibited an inhibitory effect on the transport of exogenous glucose from the host to the cyst wall, which might further promote the decomposition of endogenous glycogen for energy supply and resulted in a decrease of endogenous glycogen content in the cyst wall. PMID- 8503287 TI - [Hypotensive effect of dihydrolycorine]. AB - Dihydrolycorine-HCL(DL) is a derivative of lycorine, an alkaloid isolated from Lycoris radiata Herb. DL iv 20, 40, and 80 mg.kg-1 lowered the mean arterial pressure in pentobar-bitone-anesthetized normotensive rats, cats, and conscious rats either normotensive or renovascular hypertensive. In pithed rats DL depressed the hypertensive effect of reaction to electric stimulation to the T7-9 segments of spinal cord. DL also depressed the hypertensive effect of phenylephrine. In rabbit aorta ring and rat anococcygeus muscle, DL antagonized the contractile effect of methoxamine, with pA2 values of 5.93 and 6.35, respectively. These results suggest that DL can block alpha 1-adrenoceptors. PMID- 8503288 TI - [Effect of estradiol on the course of ovalbumin sensitization in guinea pigs]. AB - The latent period of ovalbumin (Ova)-induced asthma in Ova-sensitized guinea pigs was shorter in the ovariectomized animals with sc estradiol (E2) 400 or 50 micrograms.d-1 x 14 d and in animals with intact ovary (84 +/- 35, 82 +/- 33, and 100 +/- 32 s, respectively) than in the ovariectomized animals (140 +/- 29 s) (P < 0.05). The histamine (His) content of the lungs and His released from lungs under Ova challenge in vitro increased in the group of ovariectomy with sc E2 50 micrograms.d-1 x 14 d as compared with those without sc E2 (56 +/- 9 and 47 +/- 11 ng/g wet weight vs 44 +/- 10 and 36 +/- 11 ng/g wet weight) (P < 0.05). However, the pD2 values of the contraction of isolated tracheal strips induced by His and those of the relaxation by isoproterenol (Iso) were not affected. These findings suggest that the strengthened effect of E2 on the sensitization may be related to the content and the release of lung His in guinea pigs. PMID- 8503289 TI - A 54-kDa protein overexpressed by chloroquine-resistant Plasmodium berghei ANKA strain. AB - Using an insoluble chloroquine-adsorbent, a 54-kDa protein (with a range of 50-60 kDa) was extracted from serum of mice infected with chloroquine-resistant (CR) Plasmodium berghei ANKA strain. Immunoblotting assay with antiserum against the 54-kDa protein showed that the content of the protein was higher in serum of mice infected with the CR parasites than that of mice infected with chloroquine sensitive (CS) P berghei ANKA strain, and that instead of the 54-kDa protein, a set of 15-, 16-, and 23-kDa proteins was found to be highly overexpressed in lysate of purified CR parasites in comparison with that of purified CS parasites, suggesting the 54-kDa protein probably to be composed of 3 subunits. These findings may bear great importance in probing mechanism of chloroquine resistance in malaria parasites. PMID- 8503290 TI - Frequency of nondiagnostic findings on colposcopy: implications for management. AB - BACKGROUND: This study examines the frequency of nondiagnostic findings from colposcopic biopsies at the University of Washington Family Medical Center Colposcopy Clinic and reviews the literature for any current recommendations for management of such cases. METHODS: We reviewed 138 consecutive colposcopy reports covering the period from January 1990 to August 1991 from the Colposcopy Clinic at the University of Washington Family Medical Center. Nondiagnostic results were defined as those negative for dysplasia (atypia, inflammation, hyperkeratosis, and parakeratosis). RESULTS: Of 138 endocervical curettages 25 (18.1 percent) had nondiagnostic findings, while of 206 ectocervical biopsies 104 (50.5 percent) had nondiagnostic findings. Of the 138 patients examined, 41 (29.7 percent) had a nondiagnostic biopsy as the most notable finding. CONCLUSION: Nondiagnostic colposcopic biopsy results occur frequently at the University of Washington Family Medical Center. The meaning of these equivocal results remains unclear. We need a further study of the natural history of such patients to determine appropriate recommendations for management. PMID- 8503291 TI - Factors affecting the threshold for seeking care: the Panic Attack Care-Seeking Threshold (PACT) Study. AB - BACKGROUND: This study was conducted to explore the phenomenon of seeking medical care for panic attacks and to identify factors associated with seeking care. METHODS: A community sample of adults was screened using the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition. Subjects who had experienced panic attacks participated in a structured interview concerning their health care access and utilization, panic characteristics, comorbidity, illness attitudes and perceptions, and family characteristics. RESULTS: Forty-one percent of the subjects had not sought medical care for their panic attacks. Having to get someone to drive (RR [relative risk] = 1.8; P = 0.0026), inability to work because of panic (RR = 1.6; P = 0.0054), and a high treatment experience score on the Illness Attitude Scales (RR = 1.5; P = 0.034) independently predicted seeking care. Seeking support was also significantly associated with seeking care (t = -4.05; P = 0.0001). Care seekers tended to have more severe symptoms, stronger symptom perceptions, and more bodily preoccupation and to abuse drugs more frequently. Seeking care was not influenced by sex, race or ethnicity, stress, psychiatric comorbidity, family function, social support, or access to health care. CONCLUSIONS: Nearly one-half of persons with panic attacks do not seek care for their attacks. Those who seek care differ from those who do not in ways that have important implications for the understanding of this illness. PMID- 8503292 TI - Cardiovascular risk factor status of an Old Order Mennonite community. AB - BACKGROUND: The Old Order Mennonites are members of rural farming communities whose religious and cultural traditions pervade their dietary and health practices. These cloistered Christian communities often present special challenges to primary care physicians unfamiliar with the Mennonite way of life. Anecdotal descriptions of Mennonite customs suggest heightened risk for cardiovascular disease because of a dairy and meat-based diet and a lack of utilization of the traditional health care system. METHODS: With approval from the church bishop, households from a New York State Mennonite community were interviewed about personal and family history of cardiovascular disease, knowledge of dietary cardiovascular risk factors, and personal awareness of their cardiovascular risk factor status. A standardized Saturated Fat/Cholesterol Avoidance Scale was used to assess qualitatively the community's traditional diet. Blood pressures and total serum cholesterol levels were measured in all willing participants. RESULTS: Two hundred fifty interviews were completed. A significant difference was found between the cholesterol level of the men (181 mg/dL) and the women (192 mg/dL). When compared with the general population, the Mennonite men had significantly lower total serum cholesterol levels and systolic and diastolic blood pressures. Only 8 percent of the study population had been previously screened for serum cholesterol. One-third of the population older than 55 years had a personal history of either myocardial infarction or stroke. The study population's score on the Saturated Fat/Cholesterol Avoidance Scale indicated a diet higher in saturated fat and cholesterol than that of other study populations. CONCLUSIONS: Our findings indicate a significant lack of preventive health care practices, minimal avoidance of dietary cardiovascular risk factors, and a significant difference between men's and women's cardiovascular risk factor status in this Old Order Mennonite population. PMID- 8503293 TI - A retrospective study of patient care needs on admission to an inpatient hospice facility. AB - BACKGROUND: The care and support of dying patients and their families are among the most important skills of a family physician. In this century, an increasing proportion of deaths have occurred in hospitals with resulting medicalization of the dying process. Hospice care has emerged to focus on the relief of suffering rather than the cure of illness. This descriptive study reports information about the diagnoses, care needs, and attending physicians of a cohort of patients admitted to a free-standing, inpatient hospice program. METHODS: We undertook a retrospective chart review of 335 patients admitted to a hospice program during a 26-month period, collecting data recorded on standardized nursing assessment forms. These forms provided information on 19 biologic, functional, and psychosocial symptom groups at the time of admission. RESULTS: Family physicians were the admitting physicians in a minority of hospice admissions. Pain and mobility problems were the most frequent symptoms encountered. Other common issues included bowel, respiratory, and nutritional problems. Emotional difficulties were noted less frequently than these common biomedical problems. CONCLUSIONS: Family physicians should be trained to address core problems encountered in the care of dying patients. Multidisciplinary team approaches are essential in the management of many problems encountered in hospice care. PMID- 8503294 TI - Accuracy of patient recall and chart documentation of falls. AB - BACKGROUND: This 1-year prospective study examined the accuracy of patient recall of falls and fall injuries and completeness of chart documentation of these events. METHODS: One hundred ambulatory geriatric family practice patients reported falls weekly by postcard with telephone call follow-up. On a final postcard they reported their recall of falls and fall injuries in the preceding 3 , 6-, and 12-month periods. Patient charts were reviewed for fall documentation. RESULTS: For the 3-, 6-, and 12-month periods, respectively, 31 percent, 44 percent, and 89 percent of participants who had reported a fall recalled at least one fall. Sixty-eight percent of participants who had reported an injury recalled one at the year's end. The positive predictive value of recalling a fall was 92 percent and of recalling a fall injury was 72 percent for the 1-year period. Only 10 of 56 (18 percent) reported falls were documented in the patient's chart. CONCLUSIONS: Patients recalled falls and injuries in the previous 12 months well, but they were less accurate for recall periods of 3 and 6 months. Few reported falls were documented by the patient's physician. Awareness of falls can be increased by asking the patient about falls during the previous year and by documenting all reported and recalled falls. PMID- 8503295 TI - Hypertension in the 1990s: a new disease. AB - BACKGROUND: Recent analyses of the cumulative results of the major treatment trials of mild-to-moderate hypertension have shown only a small benefit in the prevention of stroke and no benefit in the prevention of coronary heart disease. METHODS: A MEDLINE search for articles published from 1966 to 1991 was made using the key words "left ventricular hypertrophy," "hypertension," "insulin resistance," and "cholesterol." The bibliographies of these articles and articles previously abstracted in The Family Practice Newsletter (InforMed) and the author's personal files were also sources of information. RESULTS AND CONCLUSIONS: Newer pharmacologic agents for hypertension, the peripheral alpha blockers, the calcium channel blockers, and angiotensin converting enzyme inhibitors, exert positive effects on left ventricular hypertrophy, serum lipids, and serum insulin and could be cardioprotective. These drugs offer the promise of being able to show cardiovascular benefits from the treatment of mild-to-moderate hypertension that were not realized in the earlier clinical trials. PMID- 8503296 TI - Correlation of emergency department radiographs: results of a quality assurance review in an urban community hospital setting. AB - BACKGROUND: The study objective was to compare the accuracy of radiograph interpretation by emergency and family physicians with radiologists' overreadings. METHODS: We undertook a historical chart review of patients seen consecutively during a 1-year period at an inner-city emergency department of a medium-volume community hospital. The participants were a racially mixed group of 22,141 patients for whom 12,083 radiographs had been ordered. We compared interpretations by emergency and family physicians with those of radiologists who performed overreadings within 24 hours. This intervention was performed retrospectively. Measurements consisted of descriptive statistics, such as percentages and chi-square analysis. RESULTS: The main result was an overall discrepancy rate (ODR) of 1.1 percent. This figure is significantly different (P < 0.0001) from the lowest reported overall discrepancy rate to date (2.8 percent). CONCLUSIONS: Consistently low overall discrepancy rates have specific implications for the medical practice and reimbursement of primary care physicians for radiograph interpretation. PMID- 8503297 TI - Caring for the bicultural family: the Korean-American example. AB - Bicultural families are increasing in US society, and family physicians will see more of these families for medical care. They can exhibit problems unique to their bicultural experience that arise from the stresses caused by cultural differences in such areas as family roles, emotion expression, child rearing, interpersonal relationships, and methods of communication. If coping mechanisms do not resolve these stresses, the family will come to the family physician with physical manifestations of illness or distress. The symptoms are usually related to depression or depressive equivalents. To care for these families successfully, family physicians should treat both family members and the individual patient. When caring for bicultural families, it is important to recognize the high-risk factors that put them at risk for dysfunction. Treatment goals should be centered on communication and education. In short-term counseling, support, education, listening, and referral to appropriate community resources are useful treatment modalities. PMID- 8503298 TI - Guidelines for the prediction and prevention of pressure ulcers. The Agency for Health Care Policy and Research. AB - Of the 26 recommendations made by the panel, only six (23 percent) have sufficient research data to warrant a level A or B strength of evidence rating. Thus expert opinion, while traditionally valuable for filling the gaps where research-based information is missing, is used more extensively than data to support the recommendations of this guideline. The literature on pressure ulcers is voluminous but of variable quality. After reviewing this literature, I am not surprised at the confusion and frustration that physicians feel when trying to prevent pressure ulcers. More research is needed to confirm or refute expert opinion on prevention of pressure ulcers. The guideline does, however, provide physicians five specific steps that can be used to prevent pressure ulcers in their patients: (1) perform a risk assessment on all bed- and chair-bound patients, (2) keep the pressure off the bony prominences of at-risk patients by using a turning schedule, (3) use a pressure-reducing mattress in the treatment of all at-risk patients, (4) avoid massage of bony prominences, and (5) encourage the development of institutional educational programs or skin care teams for the prevention and treatment of pressure ulcers. The remaining 20 recommendations are reasonable and can be applied selectively, but they are based on expert opinion and have not been shown to reduce the rate of pressure ulcers in well-designed research studies. PMID- 8503299 TI - Black widow spider bite. AB - These two cases illustrate many classical features of latrodectism. A subclinical bite followed by extensive systemic signs and symptoms in a recognizable pattern is strongly suggestive of the diagnosis. Pain and muscle spasms are refractory to standard therapy but are relieved by intravenous calcium. Finally, there should be complete resolution of the symptoms after only one vial of antivenin is administered. The common features of these cases form a recognizable constellation of signs and symptoms known as latrodectism. The specifics of these cases highlight the uncertainty of therapy. The older patient, because of the severity of his symptoms, warranted the use of antivenin perhaps earlier than it was given. The argument could be made, however, that because the patient was experiencing minimal morbidity and mortality, the calcium would have controlled his symptoms until the venom was cleared from his system. There would then have been no risk of anaphylaxis or serum sickness. One can only guess whether continued calcium use would have precipitated a hypercalcemic state and also would have been a health risk. The decision to provide antivenin therapy was made and the patient did well. The younger patient was not as severely affected as the older patient, so it could be argued that he was less in need of the antivenin. Still, his symptoms had not abated despite a reasonable length of time and might even have been considered to be worsening. No bite was found, but having discovered him playing with the spider certainly qualifies as circumstantial evidence. Also, the child was 11 months old and had greater risk of mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503300 TI - Natural history of a cervical cavernous hemangioma through two pregnancies. AB - Hemangiomas of the uterine cervix are extremely rare. The tumor can have a variety of appearance. When a cervical hemangioma is diagnosed in an asymptomatic nulliparous woman or during pregnancy, expectant management is warranted. Surgical intervention, laser, ablation, or Cesarean section is reserved for hemangiomas that present major problems. The natural history of cervical hemangioma is regression and involution. PMID- 8503301 TI - Exercise stress test training in family practice residency programs. AB - EST is a commonly indicated procedure in primary care medicine and as such is well suited for use by family physicians. At present there are few family physicians performing this procedure in their offices. Our survey of US family practice residency directors has shown an interest well above what would be expected for the level of current practice in the community; however, there remains an ambivalence on the need to provide EST training in the curriculum. PMID- 8503302 TI - American and French family physicians: a comparative profile. PMID- 8503303 TI - Treatment of AIDS and HIV-related conditions--1993. PMID- 8503304 TI - Panic disorder: the decision to seek health care. PMID- 8503305 TI - Nondiagnostic and inconsistent results from colposcopy. PMID- 8503306 TI - Microcomputer-based records. PMID- 8503307 TI - Headache after lumbar puncture. PMID- 8503308 TI - Single-payer system. PMID- 8503309 TI - Newsletters in family practice. PMID- 8503310 TI - Standardized functional assessment scales for elderly patients. PMID- 8503311 TI - Guillain-Barre syndrome in Oxfordshire: clinical features in relation to age. AB - We have examined the clinical features of Guillain-Barre syndrome (GBS) in a UK series with a valid epidemiological base, studying cases from a geographically defined population using enhanced data from the Oxford record linkage study and applying standard diagnostic criteria. Clinical features in patients aged > or = 60 years were compared with those aged 20-59 years. Cranial nerve involvement was found less often in old than in young adults (6/21 vs 27/41, chi 2 p < 0.02). Old patients more frequently had other diagnoses accompanying GBS (10/21 vs 3/41, p < 0.001). There were no significant differences between old and young in: occurrence or type of preceding illness; site of symptoms at onset; severity of maximal neurological impairment; sphincter dysfunction or any autonomic involvement; requirement for artificial ventilation; case fatality rate; proportion of patients with no residual disability at or before 12 months from onset; mean duration from onset to maximal neurological impairment, from onset to first signs of recovery, and from maximal neurological impairment to recovery ('plateau time'). The variety and severity of clinical features of Guillain-Barre syndrome are similar in old and young adults. PMID- 8503312 TI - The Barthel ADL index: scoring by the physician from patient interview is not reliable. AB - Using the Barthel index, a physician's ADL scoring based upon clinical interviews of 59 elderly nursing-home patients was compared with the scoring by nurses based upon observations over time (the reference method). The scoring by the doctor was higher than that by the nurses (mean score 14.3 vs 12.2), and 11.1). Use of the kappa statistics on each item of the Barthel ADL index showed that, in general, the agreement was poor between physician's scoring and the reference method. However, information collected by the physician on Barthel index items reflecting mobility demonstrated fair to good agreement among patients with a higher score on the Mini-Mental Status. PMID- 8503313 TI - The association between mental, social and physical activity and cognitive performance in young and old subjects. AB - The influence of mental, social and physical activity on fluid, crystallized and memory tasks was examined in 60 young and 56 elderly subjects using multiple regression. Once the influence of education, age, health and psychiatric morbidity was removed, physical activity was associated with higher fluid test performance in old but not in young subjects. Moreover, mental activity was associated with higher performance on fluid and crystallized tasks for subjects with low education but not for subjects with high education. PMID- 8503314 TI - Assessment in severe dementia: the Guy's Advanced Dementia Schedule. AB - Previous findings suggest that severely demented subjects are often capable of responding in some ways to stimulation. This study describes the development of a schedule which can discriminate between subjects on the basis of their responses to a range of objects of varying familiarity. The schedule includes extensive prompting to elicit a range of responses from simple taking of objects through to naming and using. The measure was found to be reliable and valid against the Clifton Assessment Procedures for the Elderly and the Mini-Mental State Examination. Scores were able to discriminate between subjects scoring 0 on the Mini-Mental State Examination. It is suggested that scores on the schedule may reflect residual cognitive capacities and orientation to the environment and as such this measure could prove useful to a range of future studies. PMID- 8503315 TI - Factors associated with decline in function, institutionalization and mortality of elderly people. AB - Movements between dependency states, institutionalization and death are investigated in a general practice cohort of people aged 75 years and over with follow-up at 5 and 7 years from initial interview. Initially, 1203 people were interviewed, 1124 living in the community and 79 in institutions. By 5 years, 42% (510) had died and by 7 years 58% (700) had died. Dependency was defined as requiring help or aids with at least one activity of daily living (ADL). Of those initially independent, 34% were still independent 7 years later. Women at each age were more likely to become dependent whilst men had higher mortality. Those rating their health as fair or poor were more likely to lose independence at both 5 and 7 years than those rating their health as good. These differences remained, even after adjustment for age, sex and baseline ADL status. With the assumption that once institutionalized a person did not return to live in the community (an assumption upheld by the present data), 7% (79/1124) of those initially resident in the community were institutionalized during the 7 years; the rates for men (6%) being slightly lower than for women (7.5%). PMID- 8503316 TI - Relationships between parathyroid hormone, 25-hydroxyvitamin D, and bone mineral density in elderly men. AB - This study aimed to determine the relationships between parathyroid hormone, vitamin D status and bone mineral density (BMD) in healthy older men. Subjects [n = 133, mean age (SD) 69.5 (3.1), range 65-76 years] were recruited from two general practices in Cambridge. Blood samples were drawn for measurement of intact parathyroid hormone (1-84, hPTH) and total 25-hydroxyvitamin D. Bone mineral density at the hip and spine was measured by dual-energy X-ray absorptiometry (DEXA). After adjusting for age and body mass index (BMI), PTH was negatively correlated with trochanteric (r = -0.24, p = 0.007), intertrochanteric (r = -0.29, p = 0.001), and Ward's Triangle BMD (r = -0.15, p = 0.087). By analysis of variance, controlling for age and BMI, PTH showed a relatively consistent downward trend with increasing tertiles of bone mineral density, especially at the hip. These results suggest a role of parathyroid hormone in determining hip bone mineral density in a community-based sample of healthy elderly men. PMID- 8503317 TI - Attitudes of relatives to autopsies of elderly patients. AB - The attitudes of 233 relatives to autopsy of elderly medical patients (mean age 82 years) who died in a district general hospital were examined prospectively. Forty-three (18%) relatives were asked permission for autopsy, 24 (56%) agreed and 19 (44%) refused. Of 190 (82%) relatives whose permission was not sought, 109 (57%) would have agreed and 81 (43%) would have refused permission had they been asked. Advancement of medicine and reassurance about the correct diagnosis were the main reasons for consent, while dislike of autopsy, family distress at disfigurement of the body and the patient 'having suffered enough' were the main reasons for refusal. Living near rather than with the deceased (64% vs 45%; chi 2 = 6.985, p = 0.01) and being a male rather than female relative (63% vs 49%; chi 2 = 3.879, p = 0.05) were predictive of a positive response to autopsy. Of the 39 autopsies performed, 24 (9.6%) followed relatives' permission and 15 (6%) were at the request of the coroner. The overall autopsy rate of 16% was lower than the rate recommended for medical audit (35%). Although there is a need for educating relatives about the benefits of autopsy, a more urgent study is required to find reasons for the low request by medical staff. PMID- 8503318 TI - Autopsy: consent, completion and communication in Alzheimer's disease research. AB - The definitive diagnosis of Alzheimer's disease remains histopathological. To date many published studies have been limited by being based on clinical diagnosis alone, which has a significant false positive rate. In a prospective, longitudinal, clinicopathological study which aims to develop an antemortem diagnostic test for Alzheimer's disease, we have achieved 96% (250/260) consent and 97% (59/61) completion rates. We here describe some of the factors we believe are responsible for these high rates and which may be relevant to other studies requiring autopsy to verify clinical diagnoses. PMID- 8503319 TI - Helicobacter pylori infection in elderly people: correlation between histology and serology. AB - A hundred elderly dyspeptic patients were studied to assess the prevalence of Helicobacter pylori infection and the correlation between histological and serological findings. Eighty-one per cent of the patients with gastritis and 63% with gastric ulcer were H. pylori positive. All patients who had H. pylori negative gastritis and gastric ulcers were on nonsteroidal anti-inflammatory drugs (NSAIDs). There were 24 patients who had evidence of H. pylori infection and were on NSAIDs. H. pylori positive patients had more dyspeptic symptoms in comparison with those who were H. pylori negative. In patients who were taking NSAIDs, the presence of severe active gastritis seemed to correlate with the presence of H. pylori but not with the use of NSAIDs. Serology had a sensitivity of 90% and a specificity of 93% with a negative predictive value of 86%. There was a significant correlation between IgG titre and the degree of inflammation and H. pylori infection. We conclude that H. pylori gastritis is the commonest histopathological finding in elderly dyspeptic patients. H. pylori infection may be an important risk factor in elderly patients who take NSAIDs, increasing their risk of gastric ulcer. H. pylori serology in elderly people has a high sensitivity and specificity comparable with those in young age groups. PMID- 8503320 TI - Bacterial surveillance cultures in a geriatric ward. AB - A study was carried out to examine the prevalence of oropharyngeal and urinary tract colonization and to compare the colonizing bacteria with the strains causing nosocomial infections during patients' stays in a geriatric ward. Colonization with Gram-negative rods was not uncommon. Nosocomial infections frequently occurred, although colonization seldom resulted in infection. Ampicillin and co-trimoxazole resistance was common in Gram-negative rods. There was little resistance to tobramycin, temocillin and quinolones in strains isolated in patients admitted from home or a nursing home. Isolates resistant to these antibiotics were found in patients admitted from other departments of the hospital, especially from the intensive care unit or during prolonged stay in the ward. Routine cultures for colonization were not predictive for subsequent infection. However, continuous monitoring of Gram-negative rods in colonization and infection remains an important instrument for a preventive policy and to guide antibiotic treatment. PMID- 8503321 TI - Lung cancer in elderly patients: the role of induced sputum production to obtain a cytological diagnosis. AB - A single induced sputum sample using hypertonic saline and a ward nebulizer was obtained from 24/26 (92%) patients prior to fibreoptic bronchoscopy for suspected bronchial carcinoma. In 11 of the 19 patients later found to have bronchial carcinoma, positive cytology was found in the induced sputum sample (58% sensitivity), with no false positives (100% specificity). These results are higher than those reported for ordinary sputum samples. They suggest a possible role for this technique in diagnosing bronchial carcinoma in elderly patients in whom bronchoscopy may be considered hazardous, or where this facility is not readily available. PMID- 8503322 TI - Care of the elderly person with diabetes: completing the audit cycle. PMID- 8503323 TI - Assessment for nursing homes in Scotland. PMID- 8503324 TI - Long-term outcome following stroke. PMID- 8503325 TI - [Significance of plasma interleukin-6 in the diagnosis of renal cell carcinoma]. AB - The significance of interleukin-6 (IL-6) in the diagnosis of renal cell carcinoma (RCC) was investigated. In RCC patients, we found that, even when IL-6 was produced by RCC, the plasma level of IL-6 was under the limit of detection in almost all patients with a classification of T2N0M0 or lower. In the case of rapidly progressive type of bulky metastasis, the concentration of IL-6 in plasma was high, but the IL-6 level correlated well with the serum C-reactive protein (CRP) level. These findings suggest that IL-6 has little potential to serve as a new tumor marker for RCC. PMID- 8503326 TI - [Influential factors on the therapeutic response in the conditioning treatment of enuresis with an original therapeutic machine]. AB - The conditioning treatment of enuresis with our original therapeutic machine, that is to awake the patient before enuresis may occur, has been performed since 1987. Influential factors on the therapeutic response were investigated. Twenty two patients with enuresis Type I were admitted and were treated for 5 nights with the therapeutic machine. Seven patients were cured (the cured group) and a certain effectiveness (decrease of the frequency of enuresis of more than 50%) was observed in 8 patients (the effective group). No effectiveness was obtained in 7 patients (the no change group). The average age of the cured group was higher than that of the no change group, and the difference was significant. No significant differences were found among the three groups in sex, the frequency of enuresis or the past experience of awakening before enuresis. Significant differences among the three groups were found in the average awakening score (how easily the patient awoke when a nurse called the patient after the machine alarmed) and the change of awakening score during treatment. The average awakening score of the cured group was the highest and that of the no change group was the lowest. The change of awakening score during treatment of the no change group was significantly lower than that of the cured group or that of the effective group. The desire to cure, scored 0-2 points at the time of discharge, was significantly stronger in the cured group than in the no change group. No significant differences were noticed among the three groups in the sleeping condition and the remembrance of awakening at the next morning. PMID- 8503327 TI - [Clinical studies on chronic prostatitis and prostatitis-like syndrome (6). Clinical evaluation for the chronic prostatitis-like syndrome patients with severe symptoms of voiding and abnormal uroflowmetric results]. AB - The relation between symptom scoring (Boyarsky symptom severity score) and their outcome of the treatments for the patients with prostatodynia were evaluated. The patients with poor outcome were examined by uroflowmetry. Twenty-two of the 236 patients with prostadodynia complained of severe symptoms of voiding (score over 7) at the first presentation. Since those patients fell into the poor outcome category by the conventional treatments (p < 0.01), there may be some possibility that this group suffered from conditions other than prostatitis or other unknown causes. The 9 patients with severe voiding symptoms and poor outcome indicated abnormal uroflowmetric results such as abnormal peak flows in 8 patients and abnormal uroflow curves in all 9 patients. This strongly suggests that these patients have lower urinary tract dysfunctions. In conclusion, measurement of Boyarsky symptom severity scores and uroflowmentry is a useful screening method for the patients with prostatodynia with severe voiding symptoms to rule out the lower urinary tract dysfunctions. PMID- 8503328 TI - [A histochemical study on the testes from patients with idiopathic male infertility: identification of acidic glycoconjugates in the seminiferous tubular walls]. AB - Acidic glycoconjugates in the seminiferous tubular walls in the testes from patients with idiopathic male infertility was identified light microscopically with the sensitized high iron diamine method in combination with digestions with chondroitinase ABC, chondroitinase B or testicular hyaluronidase. Tissue specimens were obtained by testicular biopsy from 37 patients with idiopathic male infertility and 9 fertile adult males. Chondroitin sulfate A, B and C were identified in the tubular walls of oligozoospermic patients with idiopathic male infertility irrespective of the thickness of the walls. Similar results were obtained in the tubular walls of the testes from normal males. On the other hand, chondroitin sulfate B was a main acidic glycoconjugate in the tubular walls of the testes from azoospermic patients with idiopathic male infertility irrespective of the thickness of the walls. These findings suggest that the etiological factors of the impaired spermatogenesis in patients with idiopathic male infertility are not only the disturbance of nutritional transport across the seminiferous tubular walls due to peritubular thickening but the functional alterations of the tubular walls associated with changes in components of acidic glycoconjugates in the tubular walls. The pathogenesis of oligozoospermia does not seem to be similar to that of azoosspermia since components of acidic glycoconjugates in the peritubular tissues between the two types of disorders are quite different. PMID- 8503329 TI - [Clinical study of acute scrotum]. AB - Acute scrotum is a clinical syndrome which includes various disorders. Differential diagnosis of these disorders is not always easy. We reviewed cases experienced in our hospital, focusing on diagnostic procedures. Final diagnosis in 39 cases were acute epididymitis in 23 cases, torsion of the testis in 13 cases, torsion of appendix epididymis in 2 cases and torsion of appendix testis in 1 case. It became clear ultrasonography was a useful diagnostic procedure; if the torsed portion is delineated, torsion of the testis can be diagnosed. Heterogenous echoes from the interior of the testis indicate the necrosis of the testis. Inspection was also useful; if the blue dot sign is detected, torsion of the appendix testis/epididymis is indicated. However, Doppler ultrasound did not always provide a correct diagnosis of torsion of the testis. If torsion of the spermatic cord cannot be completely ruled out, early surgical intervention and treatment are considered essential. PMID- 8503330 TI - [Complications in urological laparoscopic surgery]. AB - Laparoscopic surgery is often associated with complications which never occur in open conventional surgery. We investigated operative and postoperative complications in urological laparoscopic surgery. From February 1990 to November 1992, 91 laparoscopic operations were performed, including 62 varicocelectomies, 5 pelvic lymphadenectomies, 6 adrenalectomies, 5 simple nephrectomies, 2 radical nephrectomies, 1 staged Fowler-Stephens operation and 10 laparoscopies for cryptorchidism or other disorders. The patients ranged from 3 months to 77 years old. Nine (9.9%) of the 91 patients had complications associated with laparoscopic procedures and 4 (4.4%) of them had major complications. Pneumoextraperitoneum occurred in 3 patients. Two patients, who suffered from preperitoneal insufflation or pneumothorax associated with pneumomediastinum, failed to undergo laparoscopy. A small amount of scrotal emphysema developed in one patient, which subsided within 12 hours. Another patient, who underwent radical nephrectomy and para-aortic lymphadenectomy for left renal cell carcinoma, complained of symptoms due to persistent pneumoperitoneum and subcutaneous emphysema, which subsided 2 weeks after the operation. Respiratory acidosis caused by carbon dioxide absorption, which was difficult to be controlled, occurred in the other two patients; one was an adult male with reduced respiratory function and the other was a 1-year-and-8-month-old child. Bleeding during or after the procedure was another serious complication. Vena caval laceration occurred during right simple nephrectomy for pyonephrosis with renal calculi and was managed with laparotomy. Two patients, one after simple nephrectomy and the other after right adrenalectomy, suffered from postoperative bleeding about 300 ml through the penrose drain, which subsided following a bed rest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503331 TI - [A case of virilizing adrenocortical carcinoma in adult]. AB - A case of virilizing adrenocortical carcinoma is reported. A 35-year-old woman was referred to our clinic because of left adrenal mass detected incidentally by ultrasonography. At the time of admission, facial acne, systemic hirsutism, hypertrophied clitoris and amenorrhea for two months were observed. Serum testosterone showed obviously high level and urinary 17-KS and 17-OHCS showed slightly high level. A computed tomography revealed a heterogeneous mass with calcification in the left adrenal region. Selective angiography revealed hypervascularity. Under the preoperative diagnosis of virilizing left adrenal tumor, left adrenalectomy was performed. The tumor measured 8 x 6 x 7 cm, and weighed 194 g. A diagnosis of adrenocortical carcinoma was made by pathological examination. Virilizing adrenocortical carcinoma is very rare in adults. We reviewed and discussed 10 cases of virilizing adrenocortical carcinoma in adults, including our case, in the Japanese literature. PMID- 8503332 TI - [Long-term complete response of multiple lung metastases from renal cell carcinoma induced by combination therapy with interferon alpha and UFT: a case report]. AB - We report a case of long-term complete response of multiple lung metastases of renal cell carcinoma (RCC) by the combination therapy with interferon alpha (IFN alpha) and UFT. A 38 year-old man having left RCC with lung metastases underwent radical left nephrectomy and extended lymph node dissection, the pathological stage being pT2N2. Although metastatic lung tumors increased in size and number against intravenously admitted interferon gamma (IFN gamma) therapy after the surgery, they completely disappeared following the subsequent combination therapy with intramuscularly admitted interferon alpha (IFN alpha) and oral intake of UFT in about 2 years. The patient has been disease-free for 5 years after cessation of the treatment. Combination therapy with IFN alpha and UFT might be more effective on metastases of RCC than single use of IFN alpha or IFN gamma. PMID- 8503333 TI - [Renal cell carcinoma in a horseshoe kidney: report of two cases]. AB - We report 2 patients with renal cell carcinoma in a horseshoe kidney. A renal tumor was diagnosed during evaluation of right humeral metastatic cancer of unknown origin in case 1 (64-year-old male) and gross hematuria in case 2 (54 year-old male). Both patients underwent radical nephrectomy with division of isthmus and retroperitoneal lymph node dissection. The tumors were staged pathologically as pT2bpN0pV0pM1(oss) and pT3pN0pV1bM0, respectively. Only 27 cases of renal cell carcinoma developed in a horseshoe kidney, including the present two cases, have been reported in the Japanese literature. The blood supply to the horseshoe kidney and its evaluation by preoperative angiography were discussed. PMID- 8503334 TI - [A case of papillary renal cell carcinoma presenting as a large cyst with massive hemorrhage]. AB - A case of unusual renal cell carcinoma in a 25-year-old male is reported. The patient complained of right flank pain and a mass in the right upper quadrant of the abdomen. Selective renal arteriography revealed a hypovascular tumor at the lower pole of the right kidney. Right partial nephrectomy was performed. The mass, having a large cystic appearance with hemorrhage, was pathologically confirmed to be papillary renal cell carcinoma. We briefly discussed the specific features of papillary renal cell carcinoma in young adults and cystic changes in renal cell carcinoma. PMID- 8503335 TI - [Recurrence presenting as anuria at 16 years after partial nephrectomy for a pelvic tumor in a solitary kidney: a case report]. AB - A 61-year-old male underwent right partial nephrectomy for a pelvic tumor of a solitary kidney at the former hospital on April 1975. Two years later he had a small bladder tumor and transurethral resection was performed. Since August 1985 he had been followed up in our hospital. On June 1986, the urine cytology showed class V, but neither cystoscopy nor drip infusion pyelography revealed the tumor. On January 1992, he consulted our department with macrohematuria and anuria. Serum creatinine and blood urea nitrogen level were 17.24 mg/ml and 84.1 mg/ml, respectively. Hemodialysis was administered. Retrograde pyelography revealed a defect of tumor at the pyeloureteral junction, and pyuria by ureteral catheterization showed class V cytology. Abdominal CT showed right hydronephrosis caused by the recurrence of pelvic tumor, and right nephrectomy was performed. The histopathological diagnosis was non-papillary transitional cell carcinoma, grade 3 > 2, pT3. He is in good condition with maintenance hemodialysis. In the Japanese literature there were 16 cases of pelvic tumor on the solitary or residual kidneys. In 12 of the 16 cases, kidney sparing treatment was tried and only our case has lived over 10 years. The indication of partial nephrectomy for pelvis tumor was discussed. PMID- 8503336 TI - [Thromboangiitis obliterans of the spermatic cord: a case report]. AB - A 61-year-old man was admitted to our hospital with a 8-day history of dull pain and swelling in the bilateral scrotum and bilateral inguinal region. Neoplasma of the spermatic cord was suspected, and bilateral orchiectomy was immediately carried out. Histopathological examination revealed thromboangiitis obliterans of the spermatic cord. The differential diagnosis of a tumorous lesion in the inguinal region is frequently difficult. In such a case, surgical exploration is recommended, and a biopsy must be performed for a definitive diagnosis, but orchiectomy should not be readily selected. Our patient is the first reported case in Japan to our knowledge. PMID- 8503337 TI - [Successful artificial insemination in a patient with retrograde ejaculation following retroperitoneal lymph node dissection for testicular cancer: a case report]. AB - A 24-year-old man underwent right radical orchiectomy for testicular teratocarcinoma in May 1982, which was followed by retroperitoneal lymph node dissection. The patient showed no evidence of recurrent disease at followup examinations. The patient later reported a complete loss of ejaculation postoperatively. Erection and orgasm remained normal. Prior use of a sympathomimetic agent, imipramine hydrochloride, was unsuccessful in producing an antegrade ejaculation. Pregnancy was achieved following the fifth attempt at artificial insemination using semen retrieved from the bladder by the modified Hotchkiss method. A healthy male infant, weighing 3,150 g, was delivered. The treatment modality for male infertility due to retrograde ejaculation after retroperitoneal lymph node dissection for testicular cancer is discussed. PMID- 8503338 TI - [Phase I study of flutamide, a nonsteroidal antiandrogen, in patients with prostatic cancer]. AB - A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1,500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1,500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1,500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1,125 mg/day in the phase II study. PMID- 8503339 TI - [Clinical evaluation of flutamide, a pure antiandrogen, in prostatic cancer phase II dose-finding study]. AB - The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1,125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1,125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment. PMID- 8503340 TI - Rescuing that great resource--the autopsy. PMID- 8503341 TI - CT scans following loss of consciousness in children. PMID- 8503342 TI - Elevated LDH and Pneumocystis carinii pneumonia. PMID- 8503343 TI - Physician reimbursement. PMID- 8503344 TI - Diary from a week in practice. PMID- 8503345 TI - Practical approach to bacterial meningitis in childhood. AB - The classic triad of headache, fever and nuchal rigidity that occurs in adults with bacterial meningitis is often absent in children. Evaluation of the cerebrospinal fluid remains the gold standard for the diagnosis of bacterial meningitis. The choice of antibiotic therapy is dependent on the most likely age specific pathogen and the drug's bactericidal activity in cerebrospinal fluid. Routine fluid restriction is no longer recommended in the initial management of critically ill patients. Dexamethasone has become an important adjunct to antimicrobial therapy for meningitis due to Haemophilus influenzae type b. Prevention, especially administration of H. influenzae type b vaccine at an early age, is probably the most effective way to reduce the significant mortality and morbidity associated with bacterial meningitis in children. PMID- 8503346 TI - Autopsy: role of the family physician. AB - The rate of autopsy in the United States has declined from about 50 percent in the 1940s to less than 15 percent today. Although many clinicians feel that modern technology has made postmortem examinations obsolete, autopsies are still important for ensuring quality, assessing new technology and providing new medical information. The primary care physician is responsible for requesting autopsies when appropriate and for informing family members of the findings. Conducting a family conference is an effective method of reviewing autopsy results. PMID- 8503347 TI - Cholinesterase-inhibiting insecticide toxicity. AB - Organophosphate toxicity can be fatal. It accounts for almost 40 percent of all insecticide- and pesticide-related illnesses reported by the American Association of Poison Control Centers. Skin contamination is the most important route of occupational exposure. Carbamate insecticides exhibit a similar mechanism of acute toxicity. Organophosphate pesticides act as irreversible acetylcholinesterase inhibitors, while carbamate pesticides produce reversible effects. The inhibition of acetylcholinesterase causes accumulation of acetylcholine at nerve endings, resulting in a cholinergic or hypersecretory syndrome. Persons who are exposed to organophosphates must be admitted to the hospital for careful observation. Symptoms should be treated with atropine, and most patients should also receive pralidoxime, a cholinesterase-regenerating drug. PMID- 8503348 TI - HMG CoA reductase inhibitors for treatment of hyperlipidemia. AB - Lowering serum cholesterol levels in patients with hyperlipidemia has been shown to decrease deaths due to coronary heart disease. While diet is the mainstay of treatment for hyperlipidemia, drug therapy is necessary to achieve treatment goals in certain patients. The HMG CoA reductase inhibitors are the most effective cholesterol-lowering agents currently available. These agents are well tolerated and have few serious side effects. Their major disadvantage is their high cost. PMID- 8503349 TI - 1992 Atwater Lecture. The irresistible fascination of carotenoids and vitamin A. PMID- 8503350 TI - Bioelectrical impedance assessment of nutritional status in critically ill patients. AB - The objective of this study was to assess the utility of bioelectrical impedance analysis (BIA) in determining nutritional status in critically ill patients in the intensive care unit (ICU). Data were collected prospectively in 33 mechanically ventilated medical and surgical ICU patients requiring nutrition as part of their care. BIA, with subsequent calculation of body-composition indexes, was performed every other day for the duration of ICU stay. Body cell mass (BCM) changes correlated with energy and protein intakes (r2 = 0.87, P < 0.001 and r2 = 0.67, P < 0.001, respectively). Maintenance of BCM was achieved by a daily provision of 125.5 kJ.kg-1.d-1 (30 kcal.kg-1.d-1) and 1.5 g protein/kg whereas greater intakes allowed restoration of BCM. The mean ratios of exchangeable sodium to potassium (Nae:Ke) improved only in patients achieving positive nitrogen balance (P = 0.013). Body-composition changes determined by BIA represent a feasible adjunctive method for evaluating and monitoring nutritional status in ICU patients. PMID- 8503351 TI - Detection of small changes in body composition by dual-energy x-ray absorptiometry. AB - The ability of dual-energy x-ray absorptiometry (DEXA) to detect small changes in body composition was studied in 17 men and women during a dehydration-rehydration protocol. Scale weight (BW) and total mass (TM) from DEXA were highly related (r > 0.99) as were estimates of fat-free mass (r = 0.99) and percent fat (r = 0.97) from DEXA and densitometry. Changes in BW of approximately 1.5 kg due to fluid loss and gain were highly correlated (r = 0.90) with both changes in TM and soft tissue mass (STM) by DEXA but less so (r = 0.67) with changes in lean-tissue mass (LTM). Mean changes in TM, STM, and LTM were not different (P > 0.05) from changes in BW. Estimates of bone mass and fat were unaffected by changes in hydration. We conclude that DEXA is able to detect small individual changes in TM and STM and is also useful for detecting group changes in LTM. PMID- 8503352 TI - Decreased glucose-induced thermogenesis at the onset of obesity. AB - To investigate the possible existence of a defect of thermogenesis at the onset of obesity, we studied glucose-induced thermogenesis (GIT) during an oral glucose tolerance test (OGTT) (1 g/kg body wt) in 12 women who were at the onset of obesity (group A) compared with 12 long-standing obese women (group B) and 8 lean control subjects. During OGTT hyperinsulinemia and glucose intolerance were measured in group B, suggesting an insulin-resistant state, but not in group A. A similar defect in GIT occurred in both obese groups (8.9 +/- 1.5% in control subjects vs 4.2 +/- 1.1% in group A and 4.3 +/- 1.0% in group B, P < 0.05) despite the absence of alteration in nonoxidative glucose metabolism. We conclude that a decrease in GIT already exists at the onset of obesity, which supports the hypothesis of a possible involvement of this defect in the genesis of obesity. PMID- 8503353 TI - Hepatic response to a very-low-energy diet and refeeding in rats. AB - Hepatic effects of very-low-energy diets (VLEDs) and refeeding were studied in dietary obese rats. Rats weighing 490-530 g (ages 72-119 d) were randomly assigned to control (C) and VLED groups. Control animals consumed a complete diet ad libitum whereas VLED animals consumed 20% of the energy intake of C animals for 7, 14, or 21 d, and some VLED animals were refed the C diet for 7 d. Hepatic weights, lipid, DNA, and total protein decreased in VLED animals. Observed hepatocytic lipid was high in C and progressively decreased in VLED rats. Hepatocytes from VLED rats lost cytoplasmic organelles, contained myelin figures, and became smaller. Decreased protein-DNA ratios and lipids in these same animals is consistent with atrophy. Other biochemical findings included reductions in blood urea nitrogen, albumin, triglycerides, total protein, and glucose, all of which are synthesized or metabolized by the liver. These observations suggest that attenuation of hepatic function is likely. PMID- 8503354 TI - Use of the [14C]aminopyrine breath test to assess the hepatic response of dietary obese rats to a very-low-energy diet. AB - The intake of a very-low-energy diet (VLED) complete in all essential nutrients decreases liver mass and total liver protein in dietary obese rats. To determine how these findings may affect hepatic drug metabolizing activity, the aminopyrine breath test was performed in nine male dietary obese Sprague-Dawley rats weighing 440-460 g. Animals were maintained on a VLED, and at 0, 14, and 21 d were injected with 9.25 k Bq (0.25 microCi) [dimethylamine-14C]aminopyrine and placed in airtight restraining cages; exhaled 14CO2 was collected for 120 min. VLED animals had an increased half-life of exhaled 14CO2 (P < 0.01) and a decreased rate constant of aminopyrine elimination (P < 0.01) consistent with decreased N demethylation of aminopyrine. Decreased liver glutathione suggests reduced ability to detoxify drugs through this conjugation pathway. These studies suggest that animals on VLEDs have reduced capacity for demethylation of aminopyrine as measured by oxidative elimination of 14CO2, and may exhibit decreased metabolism of other drugs. PMID- 8503355 TI - Meal-frequency effects on plasma hormone concentrations and cholesterol synthesis in humans. AB - To examine meal-frequency effects on circulating hormone concentrations and cholesterol synthesis, male subjects consumed liquid diets given as either six evenly spaced (ES) or three diurnal (DI) meals over 3 d. Deuterium oxide was given on day 2 and blood sampled every 4 h over days 2 and 3 to measure plasma cholesterol, glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) concentrations and cholesterol synthesis. Cholesterol synthesis was determined from deuterium incorporation into plasma free cholesterol by using constrained and unconstrained curve-fit models. Plasma total cholesterol concentrations decreased in both ES and DI groups (P < 0.05). The ES group had lower insulin (P < 0.05) and GIP (P < 0.001) concentrations compared with the DI group. Cholesterol synthesis was reduced (P < 0.01) in the ES vs the DI group when determined by using constrained (0.050 +/- 0.002 vs 0.075 +/- 0.005 pools/d, respectively) and unconstrained (0.072 +/- 0.005 vs 0.119 +/- 0.011 pools/d, respectively) models. These data suggest meal frequency-dependent control of cholesterogenesis via hormonally mediated mechanisms. PMID- 8503356 TI - Dietary fat and serum lipids: an evaluation of the experimental data. AB - Regression analysis of the combined published data on the effects of dietary fatty acids and cholesterol on serum cholesterol and lipoprotein cholesterol evaluated with groups of human subjects shows that 1) saturated fatty acids increase and are the primary determinants of serum cholesterol, 2) polyunsaturated fatty acids actively lower serum cholesterol, 3) monounsaturated fatty acids have no independent effect on serum cholesterol and, 4) dietary cholesterol increases serum cholesterol and must be considered when the effects of fatty acids are evaluated. More limited data on low-density-lipoprotein cholesterol (LDL-C) show that changes in LDL-C roughly parallel the changes in serum cholesterol but that changes in high-density-lipoprotein cholesterol cannot be satisfactorily predicted from available data. PMID- 8503357 TI - Stability of n-3 fatty acids in human fat tissue aspirates during storage. AB - The content of n-3 (omega 3) polyunsaturated fatty acids in fat tissue is an indicator of their long-term consumption. Therefore, a method for determining n-3 fatty acids in human fat tissue microbiopsies was validated and the stability of n-3 fatty acids in biopsies was checked under various conditions of storage. Methyl esters were prepared from 25 to 35 mg adipose tissue and separated by capillary gas chromatography. Recovery of added eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was 98-105%. The change after storage of fat samples at room temperature or at 4, -20, or -80 degrees C for 3 mo averaged +3.3% for EPA and +2.1% for DHA, with no effect of temperature. Storage at +20 or -80 degrees C for 7 mo yielded no perceptible change in EPA, DHA, or five other n-3 polyunsaturated fatty acids. EPA and DHA concentrations in adipose tissue aspirates are remarkably stable and deserve attention as biomarkers in epidemiological studies. PMID- 8503358 TI - Relative nutritional efficacy of arginine and ornithine salts of alpha ketoisocaproic acid in traumatized rats. AB - The relative dietary efficacy of arginine alpha-ketoisocaproate (AKIC) and ornithine alpha-ketoisocaproate (OKIC) is evaluated in a rat (Sprague-Dawley) trauma (bilateral femur fracture) model. Both control and traumatized rats were starved for 2 d and then pair-fed for 2 or 4 d one of three liquid diets: diet 1 was a basic casein diet; diets 2 and 3 were the basic diet in which 10% of nitrogen was replaced by AKIC or OKIC nitrogen, respectively. Irrespective of the diet, the protein-efficiency ratio, defined as the gain in body weight per grams nitrogen consumed, was 27% less in traumatized rats than in control rats. More improvement in apparent nitrogen balance, particularly in traumatized rats, was seen with the AKIC supplement. Plasma amino acid patterns demonstrated stimulation of net protein synthesis with AKIC and not with OKIC. Dietary supplementation with AKIC may be beneficial to promote nitrogen economy in trauma victims. PMID- 8503359 TI - Carbohydrate balance and the regulation of day-to-day food intake in humans. AB - The hypothesis that carbohydrate stores are an important determinant of voluntary food intake was tested by covert dietary manipulation of carbohydrate stores in nine men during 2 d of continuous whole-body calorimetry that provided half hourly monitoring of energy and fuel balance. On day 1 subjects were fed diets intended to maintain energy balance but containing carbohydrate at either 3% (depletion) or 47% (control) energy. Average carbohydrate balance changed by 153 +/- 42 g (mean +/- SD). Subsequent (day 2) ad libitum food intake from a normal diet of fixed macronutrient composition was identical on the control and depletion protocols: 12.73 +/- 2.24 and 12.72 +/- 2.01 MJ, respectively. The carbohydrate-depletion protocol caused a suppression of carbohydrate oxidation (174 +/- 41 vs 256 +/- 39 g, P < 0.001) and a reciprocal elevation in fat oxidation (120 +/- 11 vs 89 +/- 12 g, P < 0.001). These readjustments in fuel utilization were the primary mechanism for re-establishing carbohydrate balance. This study does not support the hypothesis that the need to maintain specific carbohydrate stores is a determinant of food intake in the short term. PMID- 8503360 TI - Vitamin A deficiency among children in a periurban South African settlement. AB - Preschool children (aged 3-6 y) who were living in an informal settlement within metropolitan Durban, South Africa, were assessed for vitamin A status. The serum retinol concentration of 169 children tested was 0.73 +/- 0.26 mumol/L (mean +/- SD). Nine children (5%) had vitamin A deficiency (< 0.35 mumol/L) and 75 children (44%) had low vitamin A concentrations (< 0.70 mumol/L). Conjunctival impression cytology (CIC) in 185 children revealed that 18% had poor vitamin A status as defined by two abnormal conjunctival specimens. The CIC test was a feasible and reproducible method; however, it correlated poorly with the traditionally accepted serum retinol threshold of deficiency in this population where overt vitamin A deficiency is not prevalent. This survey demonstrated that regardless of the measurement tool, there is a prevalence of subclinical vitamin A deficiency in this typical periurban informal settlement and accordingly we suggest that these children should be targeted for vitamin A-intervention strategies. PMID- 8503361 TI - Day-to-day variation of the glycemic response in subjects with insulin-dependent diabetes with standardized premeal blood glucose and prandial insulin concentrations. AB - To study the day-to-day variation in the glycemic response to a starch-rich meal in subjects with insulin-dependent diabetes mellitus (IDDM), eight young subjects with IDDM were served test meals of 100 g white bread on 3 separate days. They had achieved normoglycemia 2 h before the test meals by means of a glucose clamp and a constant insulin infusion was provided during the study period. Mean areas under the response curves of blood glucose to the three meals (above basal) were not different: 1067 +/- 93, 1028 +/- 91, and 970 +/- 42 mmol/L x 180 min (NS) and no difference in insulin concentrations was found. The mean (+/- 95% confidence interval) of blood glucose area under the response curves for one test meal was 1067 +/- 230 mmol/L x 180 min and for the test meal repeated three times was 1021 +/- 133 mmol/L x 180 min. Intra- and interperson components of variance were 26% and 74%, respectively, of the total variance of blood glucose areas. PMID- 8503362 TI - Thermic effect of infused amino acids in healthy humans and in subjects with insulin resistance. AB - The thermic effect of food has been observed to be decreased in subgroups of obese nondiabetic and obese diabetic subjects. The mechanisms responsible for this decrease have not been fully elucidated. Although protein elicits the largest thermic effect among the various nutrients, most studies have addressed carbohydrate- or fat-induced thermogenesis in insulin resistance. To determine whether the decreased thermic effect of nutrients in insulin-resistant patients could be related to a decrease in protein-induced thermogenesis, glucose [13.9 mumol.kg fat-free mass (FFM)-1.min-1] with or without amino acids (4.2 mg.kg FFM 1.min-1) was infused into a group of six obese nondiabetic subjects (Ob), six obese subjects with non-insulin-dependent diabetes mellitus (NIDDM), and six lean subjects. The thermic effect of infused amino acid (% of infused energy) measured by indirect calorimetry was 21.1 +/- 3.2%, 23.8 +/- 1.8%, and 20.0 +/- 2.9% in lean, Ob, and NIDDM subjects, respectively (NS). It is concluded that the thermic effect of protein is not altered in insulin-resistant patients. PMID- 8503363 TI - Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I. AB - Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2) 1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease. PMID- 8503364 TI - Secular trends in dietary intakes and cardiovascular risk factors of 10-y-old children: the Bogalusa Heart Study (1973-1988). AB - Dietary intakes of 10-y-old children were examined in six cross-sectional surveys to observe secular trends in energy, macronutrient, cholesterol, sodium, and fatty acid intakes. Total energy intake remained unchanged from 1973 to 1988; however, when expressed as energy/kg body wt, intake decreased from 275.1 kJ (65.5 kcal) in 1973 to 254.9 kJ (60.7 kcal) in 1988 because children's weight increased. Linear trends over this time period were also noted for total fat (negative), saturated fatty acid (negative), polyunsaturated fatty acid (positive), dietary cholesterol (negative), and sodium intake (positive). There was a significant increase in percent energy from protein and carbohydrate and a significant decrease in percent energy from fat, primarily saturated and monounsaturated fatty acids. An apparent increase over time is noted in the percent of children meeting dietary recommendations for total fat, saturated fatty acid, and cholesterol. Yet, few children meet the prudent diet recommendations. PMID- 8503365 TI - Milk of patients with tightly controlled insulin-dependent diabetes mellitus has normal macronutrient and fatty acid composition. AB - The composition of macro- and micronutrients in milk from six patients with tightly controlled insulin-dependent diabetes mellitus [median glycosylated hemoglobin concentrations at parturition of 5.2% (range 4.9-5.3%, reference range 4.9-6.6%) and 6 wk thereafter of 6.1% (range 5.0-6.3%, reference range 5.0-6.4%) was compared with that from five control subjects. Milk samples were collected halfway through a single breast-feeding at days 3-5 (colostrum); 7, 9, and 10 (transitional milk); and 12, 15, 17, 21, 25, 29, and 35 (mature milk). We found no abnormalities in macronutrient (triglycerides, lactose, and protein), cholesterol, glucose, and myoinositol concentrations or fatty acid composition. Two of three longitudinally studied patients showed rather constant ratios between glucose concentrations in milk and capillary blood. The present data suggest that tight control corrects a multitude of milk abnormalities associated with moderate and poor control. PMID- 8503366 TI - Urinary and fecal endogenous calcium excretion in the age range of 5-15 y. PMID- 8503367 TI - Safety of amino acids used as dietary supplements. PMID- 8503368 TI - Serum lipid concentrations and trans-fatty acid intake. PMID- 8503370 TI - SI units and common sense. PMID- 8503369 TI - The impedance index in predicting total body water. PMID- 8503371 TI - The colonic adenoma-carcinoma: sequence revisited. PMID- 8503372 TI - Diagnosis of pseudo-obstruction in children. PMID- 8503373 TI - Barrett's esophagus: congenital or acquired? AB - Barrett's esophagus (BE) is a premalignant condition in which metaplastic specialized columnar epithelium with goblet cells is present in the tubular esophagus. BE is much more prevalent in adults than in children, but largely because of its occurrence in children, a congenital etiology for BE has been proposed by some. However, there is extensive, compelling evidence to indicate that Barrett's specialized metaplasia is an acquired disorder in children and adults, resulting from both a severe mucosal injury and an abnormal intraesophageal milieu during mucosal repair. Acid reflux has been emphasized as being the usual inciting and ongoing injurious factor, but more recently the additional importance of refluxed duodenal contents has been recognized. Despite recent advances in our understanding, it remains unclear why pathologic gastroesophageal reflux results in squamous esophagitis in some persons and Barrett's specialized metaplasia in others. Although the evidence cited for a purely congenital cause of BE can be readily refuted, a congenital component in combination with severe mucosal injury cannot be ruled out. PMID- 8503374 TI - Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. AB - Six hundred twenty-one asymptomatic persons with negative fecal occult blood tests (ages 50-75 yr), including 496 with no known risk factors for colorectal cancer and 125 with a single first-degree relative with a history of colonic neoplasia developed after age 40, underwent screening colonoscopy. Three Dukes A cancers were detected in average-risk persons. The overall prevalence of adenomatous polyps was 27%. Multiple logistic regression analysis revealed that increasing age and male gender were both strong predictors of colonic neoplasia (p < 0.001). A positive family history of a single first-degree relative with colorectal cancer was not associated with an increased prevalence of colonic neoplasia (p = 0.29), although an effect may be present if the relative was < 60 yr at diagnosis. Overall 16% of males and 7% of women > or = 60 yr had at least one adenoma that was large (> or = 1 cm in size), villous or tubulovillous, or had grade 3 dysplasia. We conclude that the prevalence of colonic neoplasia in asymptomatic persons with negative fecal occult blood tests is substantial, particularly in elderly males. A family history of a single first-degree relative diagnosed at age > or = 60 yr with colorectal cancer is not associated with an increased prevalence of colonic adenomas. PMID- 8503375 TI - Predicting the clinical response to cisapride in children with chronic intestinal pseudo-obstruction. AB - We assessed upper gastrointestinal anatomy and function with contrast radiology and antroduodenal manometry in 51 children with chronic intestinal pseudo obstruction (CIP) prior to entering these patients into an open-label outpatient trial of cisapride. The diagnosis of CIP was based on characteristic symptoms requiring special nutritional support (parenteral in 30, tube feeding in 12) or interfering with daily activities (documented by diary in nine). At a time the subjects were not acutely ill, antroduodenal pressures were recorded for > 4 h fasting and > 1 h after a complex liquid meal. Results were categorized by the most prominent manometric abnormality as myopathy (n = 6), absent migrating motor complex (MMC) (n = 27), failure to induce fed pattern (n = 7), MMC plus discrete abnormalities (n = 7), and postprandial duodenal hypomotility (n = 4). Patients in the first two categories did not have effective MMCs, but those in the last three categories did. Compared to children without MMCs, those with MMCs rarely required parenteral nutrition (p < 0.001). All children were treated with oral cisapride 0.2 mg/kg/dose t.i.d., and evaluated every 2 months for up to 1 yr. Of 49 evaluable subjects, the final global assessment was unchanged in 25, fair (improved symptom score) in 17, or excellent (change from TPN to tube feeding or tube feeding to oral feeding) in seven. Children with MMCs (13 of 18) responded more often to cisapride than those without MMCs (11 of 31), p < 0.02. All four subjects with postprandial duodenal hypomotility had excellent responses. Children with normal diameter bowel responded more often than those with dilated bowel, p < 0.004. To summarize, in children with CIP, absence of the MMC was associated with need for greater intensity of nutritional support and decreased response rate to cisapride. The response to cisapride was highly variable within the study group, but often could be predicted by the presence or absence of bowel dilation and MMCs. PMID- 8503376 TI - Esophageal motility in low-grade reflux esophagitis, evaluated by stationary and 24-hour ambulatory manometry. AB - Whereas previous studies have unequivocally shown that esophageal motility is abnormal in patients with severe reflux esophagitis, the results of motility testing in patients with low-grade esophagitis are inconsistent. We studied 27 patients with Savary grade I and II esophagitis and 24 healthy controls matched for age and sex. Both underwent conventional manometry and 24-h ambulatory pH and pressure monitoring. Esophageal acid exposure was greater in patients than controls. The mean lower esophageal sphincter pressure was significantly lower in esophagitis patients [1.46 +/- 0.09 vs. 1.79 +/- 0.11 kPa (10.98 +/- 0.68 vs. 13.46 +/- 0.83 mm Hg)]. The total number of contractions recorded in the 24-h period was not different in the patient group (2168 +/- 108.4 vs. 2033 +/- 130.5), but esophagitis patients had an increased number of nontransmitted contractions (968 +/- 39.4 vs. 773 +/- 50.2, p < 0.01). A tendency toward a decreased prevalence of peristaltic contractions just failed to reach statistical significance (p = 0.07). Both conventional manometry and 24-h monitoring showed no significant difference in peristaltic amplitude between the two groups. Differences in contraction duration (2.02 +/- 0.08 vs. 2.39 +/- 0.12 s, p < 0.01) and velocity of the peristaltic wave (3.65 +/- 0.10 vs. 4.63 +/- 0.13 cm/s, p < 0.01) were only detected by 24-h monitoring. The findings made in this study do not support the concept that impaired esophageal peristalsis is a major factor in the pathogenesis of low-grade esophagitis. PMID- 8503377 TI - Significantly reduced acid detection at 10 centimeters compared to 5 centimeters above lower esophageal sphincter in patients with acid reflux. AB - Ambulatory pH monitoring of the esophagus is carried out by positioning a pH sensor 5 cm above the lower esophageal sphincter (LES). There are several techniques to locate the LES, and each method has a different margin of error. This work used dual pH sensors to monitor simultaneously at two different levels (5 and 10 cm above the LES) in order to establish the possible magnitude of error that could arise from inaccurate placement of a pH probe. Thirty-four patients with symptoms of gastroesophageal reflux (GER) were studied. They were grouped as 20 patients with pathological reflux (GER group) and 14 patients with physiological reflux, based on a reflux score derived by Johnson and DeMeester for distal esophageal pH monitoring. When the reflux scores were compared, the difference between the two monitoring levels was statistically significant in the GER group (p < 0.001) but not in the physiological reflux group (p = 0.09). In the GER group, the difference in the Johnson and DeMeester score accounted for a change in clinical diagnosis in nine of the 20 patients if the pH probe was placed at 10 cm above the upper margin of LES. Proximal reflux episodes (10 cm above LES) were preceded by distal reflux episodes (5 cm above LES) in 97% (878/901) of cases. Accurate probe placement is essential in the diagnosis of GER. PMID- 8503378 TI - Segmental versus diffuse nutcracker esophagus: an intermittent motility pattern. AB - The most common esophageal motility abnormality in patients with noncardiac chest pain is nutcracker esophagus. Most investigators regard nutcracker esophagus as a diffuse process involving the distal esophagus. Others consider it a segmental disturbance affecting isolated regions of the distal esophageal smooth muscle. This study compared the prevalence, clinical features, consistency, and manometric course of patients with either segmental high-amplitude peristaltic contractions (SHAPC) or those with the traditional diffuse contraction abnormalities termed nutcracker esophagus (NE). We particularly sought to determine whether patients with SHAPC represent an early spectrum evolving into a more diffuse contraction disorder--NE. The prevalence and clinical features of patients with either motility disturbance were similar. Thirty-nine percent of our patients had abnormally high peristaltic amplitude in locations of the proximal esophagus not previously described. Follow-up manometric studies demonstrated that only 53% of patients in the NE and 20% with SHAPC retained the same manometric diagnosis. In addition, 33% of patients in the NE group and 40% of the SHAPC group permutated into each other. These findings indicate that patients with SHAPC do not represent an early process subsequently evolving into a more diffuse contraction abnormality. Rather, the motility pattern of high amplitude peristaltic contractions--segmental or diffuse--constitutes a labile marker associated with noncardiac chest pain. PMID- 8503379 TI - Predictors and the rate of medical treatment failure in ulcerative colitis. AB - Eighty-nine admissions into Auckland Hospital with exacerbation of ulcerative colitis (between May 1985 and May 1991) were analyzed to determine the rate and any predictors of medical treatment failure. Twenty-five patients (28%) failed to respond to medical treatment and required surgery. Clinical information and laboratory indices available within 24 h of the admissions were compared between the patients requiring surgery and those who did not. There were no significant differences between the groups in sex distribution, age of onset of disease, duration of disease, hemoglobin concentration, or white cell count. However, "severe" diarrhea (chi 2 = 24.83, p = 0.0001), and lower albumin level (F1, 83 = 45.61, p = 0.0001) were noted in the surgical group. There was a tendency toward higher ESR (F1, 82 = 3.06, p = 0.08) and "extensive" colitis (chi 2 = 3.29, p = 0.07) in the patients requiring surgery. Univariate analysis confirmed albumin level and severity of diarrhea as significant discriminators. A discriminant function analysis showed that albumin level and severity of diarrhea would distinguish between surgical and nonsurgical outcome in 82% of cases. Distal colitis and mild to moderate diarrhea had negative predictive values of 80% and 91%, respectively, for nonsurgical outcome of acute ulcerative colitis. It is concluded that the above significant variables are good predictors of outcome of medical treatment for exacerbations of ulcerative colitis and that the proportion of patients needing surgery has not changed in the last 35 yr despite various management strategies. PMID- 8503380 TI - Prognostic significance of hepatic venous pressure gradient in medically treated alcoholic cirrhosis: comparison to aminopyrine breath test. AB - In a long-term survival study, we compared the prognostic significance of the hepatic venous pressure gradient and of the aminopyrine breath test (ABT) in 99 alcoholic cirrhotic patients. Thirty patients survived and had a complete follow up for at least 4 yr. Mean hepatic venous pressure gradient was 19.1 +/- 5.8 mm Hg (range 8-35 mm Hg). Variceal rupture occurred only when the gradient was > or = 12 mm Hg. Variceal bleeding was observed exclusively in patients with large varices. Survival was not influenced by the level of gradient. We used the ABT to classify patients into three groups (group I, ABT > or = 2%; group II, 1% < or = ABT < 2%; and group III, ABT < 1%). Survival was significantly higher in group I than in group II (p < 0.05) or III (p < 0.01), indicating a better prognosis at a residual functional hepatic cellular mass of about 50% of the lower limit of normal value. PMID- 8503381 TI - Effect of intravenous midazolam on esophageal motility testing in normal human volunteers. AB - This study evaluates midazolam's immediate pharmacological impact on esophageal motility. Stationary esophageal motility in normal male volunteers was evaluated to obtain a baseline study. Immediately after the baseline study, each subject received midazolam 0.02 micrograms/kg intravenously, and underwent repeat manometry 5 min later. Midazolam produced a variety of motility changes. There was a decrease in upper esophageal sphincter resting pressures (p < 0.05). Median pressures increased in the esophageal body at 3 cm below the upper esophageal sphincter (p < 0.05). Lower esophageal sphincter residual pressure increased, and the percentage of relaxation decreased (p < 0.05). The most striking change was the induction of tracings consistent with nonspecific esophageal motility disorders (p < 0.01). On the basis of these results, we conclude that esophageal motility testing should not follow procedures in which midazolam is used, until the duration of its effects on the esophagus is known. PMID- 8503383 TI - Esophageal function in systemic sclerosis: a prospective evaluation of motility and acid reflux in 36 patients. AB - Systemic sclerosis (SSc) is a connective tissue disorder which frequently involves the esophagus, with severe gastroesophageal reflux (GER) and dysphagia as clinical consequences of esophageal dysmotility. The relationship between the severity and extent of esophageal acid exposure and the specific manometric disturbances has received little attention. Similarly, a paucity of manometric data exists regarding pharyngeal/upper esophageal sphincter (UES) function in SSc patients. We prospectively studied 36 SSc patients using computerized solid-state manometric and ambulatory dual-pH (upper and lower esophageal) monitoring, to define further the relationship between esophageal dysmotility and severity of GER in these patients. Patients were separated for analysis into two subgroups based on the absence (group 1, N = 25) or presence (group 2, N = 11) of distal esophageal peristalsis. SSc disease variant (diffuse vs. limited) and duration of illness were inaccurate predictors of the presence and severity of esophageal involvement. The mean lower esophageal sphincter (LES) pressure for the SSc patients (15.8 +/- 1.2 mm Hg, mean +/- SE) was significantly lower (p < 0.01) than that for a control group (26.0 +/- 2.1 mm Hg). There was no significant difference between the mean LES pressure for group 1 (15.0 +/- 1.6 mm Hg) and group 2 (17.5 +/- 1.6 mm Hg) patients. Although distal esophageal aperistalsis was noted in 70% of patients, normal proximal esophageal contraction pressures were documented in all cases. Mean UES pressure was significantly (p < 0.01) lower in group 1 (52.5 +/- 4.6 mm Hg) than in group 2 (80.5 +/- 10.6 mm Hg). The mean duration of UES relaxation and the mean time interval between the onset of UES relaxation and onset of pharyngeal contraction were significantly (p < 0.05) shorter for group 1 than group 2 patients. Pharyngeal pressures, peristalsis, and other aspects of pharyngeal/UES coordination were normal. Excessive distal esophageal acid exposure was often seen in patients in both subgroups, but it was significantly (p < 0.01) greater in group 1. Excessive proximal esophageal acid exposure was documented only in patients with absent distal peristalsis. Linear regression analysis revealed a poor correlation between the severity of esophageal acid exposure and the LES pressure. Thus, the severity and extent of GER in SSc is most closely related to the integrity of distal esophageal peristalsis. PMID- 8503382 TI - Ulcerative colitis and antineutrophil cytoplasmic antibodies in Hong Kong Chinese. AB - Inflammatory bowel diseases are known to be rare among the Chinese. The diagnosis of ulcerative colitis has been difficult in some of the Asian countries where infective colitis is more prevalent. Twenty-three Hong Kong Chinese patients diagnosed to have ulcerative colitis were reviewed. The symptoms were relatively mild and extraintestinal manifestation had been rare. Patients responded well to steroid therapy and sulfasalazine. Three patients in this series were found to have cyst and/or trophozoites of Entamoeba histolytica in stool. In this series, 19 patients were tested for antineutrophil cytoplasmic antibody (ANCA). Fourteen patients (73.5%) were positive, of which six (31.5%) showed a perinuclear staining pattern and eight (42%) demonstrated a cytoplasmic pattern. Five patients (26.5%) were negative for any ANCA, and none was positive for both. Sera of these patients were also tested for anti-alpha granules, anti-myeloperoxidase, and anti-lactoferrin activities. None was positive. Control sera collected from 16 patients with irritable bowel syndrome were all negative for the tests. In conclusion, testing of ANCAs may help in making the diagnosis of idiopathic inflammatory bowel disease in difficult situations. PMID- 8503384 TI - Prevalence of colonic neoplasia in patients with Barrett's esophagus. AB - Recent reports have suggested that there might be an increased risk of colonic adenomas and cancer in patients with Barrett's esophagus. We conducted a controlled prospective study investigating the risk of colonic neoplasia in 17 patients with Barrett's esophagus. Six additional patients with previous colonoscopy were considered separately. The prevalence of colonic neoplasia in these patients was compared with that in a group of 25 asymptomatic subjects participating in a screening colonoscopy study. There were three adenomas (17.6%) in the Barrett's group and 11 (44%) in the control group. Including the six Barrett's patients with previous colonoscopy, the rate was 30.4%. No cancers were found in either group. We conclude that the rate of colonic adenomas is no higher in a group of patients with Barrett's esophagus than in a group of matched asymptomatic subjects. The presence of Barrett's esophagus does not justify a special colonoscopic surveillance program. PMID- 8503385 TI - Fat absorption in patients with functional intestinal lymphangiectasia and lymphangiectic cysts. AB - Nine patients with endoscopically identified dilated lacteals of the duodenum were studied for evidence of pathologic intestinal lymphangiectasia. Three of the nine patients also had lymphangietic cysts in association with dilated lacteals. Duodenal biopsies, laboratory data, and imaging studies were performed in each patient. In addition, a 14C triolein fat absorption study was performed to assess subclinical malabsorption. Biopsies revealed dilated lymphatic channels in all patients, but laboratory studies failed to suggest intestinal losses of protein or fat, and radiographic abdominal imaging failed to define any of the causes of secondary lymphangiectasia. Eight of the nine patients had adequate fat absorption as measured by the 14C triolein breath test. Our data suggest that patients with incidentally discovered dilated lacteals and no clinical evidence of malabsorption may have a functional intestinal lymphangiectasia. Follow-up endoscopy probably is not warranted in this population. PMID- 8503386 TI - Clostridium difficile infection is a treatable cause of diarrhea in patients with advanced human immunodeficiency virus infection: a study of seven consecutive patients admitted from 1986 to 1992 to a university teaching hospital. AB - Of 427 human immunodeficiency virus-seropositive patients admitted to the Robert Wood Johnson University Hospital from January 1986 through August 1992, seven had Clostridium difficile enteric infection documented by the presence of cytotoxin B in the stool, without other enteric infection. All seven patients had AIDS, and all had recently received antibiotics. These patients had a severe clinical presentation of C. difficile infection. All patients had profound watery diarrhea, with a mean of 20 +/- 14 (SD) bowel movements per day. Four had fever > 38.5 degrees C, and another had hypothermia. Three patients had borderline hypotension, and another was orthostatic. The mean pulse was 119 +/- 26 (SD) beats/min. Five patients had abdominal pain and tenderness. Two had occult blood in the stool. Four had metabolic derangements such as hyponatremia, hypokalemia, or prerenal azotemia. Three of four patients undergoing abdominal roentgenography had radiographic findings consistent with severe colitis of colonic dilation, mural thumbprinting, or mural thickening. Sigmoidoscopic findings ranged from diffuse erythema to prominent pseudomembranes. During a mean interval of 14.3 +/- 6.2 (SD) days before institution of specific antibiotic therapy, the diarrhea spontaneously resolved in only one of the seven patients. In the others, the diarrhea resolved on average 7.3 +/- 4.0 (SD) days after instituting antibiotic therapy. During a mean follow-up of 4.4 +/- 6.3 (SD) months, only two patients redeveloped diarrhea. Both patients had recurrent C. difficile colitis; the symptoms again rapidly resolved after repeat antibiotic therapy. We conclude that in patients with AIDS C. difficile may present as a severe enteric infection with profound diarrhea due to immunosuppression, that the diarrhea may be prolonged and not remit spontaneously, and that the diarrhea usually rapidly resolves with specific antibiotic therapy. PMID- 8503387 TI - Pulmonary function changes after large volume paracentesis. AB - Large volume paracentesis (LVP) is a safe, rapid, and effective treatment of ascites in cirrhotic patients. We investigated the effects of a 5-L aspiration of ascites on pulmonary function parameters in eight hemodynamically stable patients with cirrhosis and tense ascites. None had known lung disease or abnormal chest roentgenograms. At baseline, mean lung volumes, diffusing capacity, and arterial pO2 were all reduced from normal predicted values. Airflow, however, when related to lung volume, was normal. Post-LVP, lung volumes increased significantly; the mean expiratory reserve volume showed the greatest percent increase (105%) and correlated with the increases in the vital capacity, functional residual capacity, and total lung capacity. Airflow, the mean diffusing capacity, and arterial oxygenation were not significantly changed after LVP. We conclude that LVP significantly increases indices of lung volume but does not significantly alter parameters of airflow or gas exchange. PMID- 8503388 TI - Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma. AB - The expression of blood group-related antigens of the Lewis system in normal gastric mucosa, intestinal metaplasia, gastric adenoma, and gastric carcinoma was examined. Ninety-five percent of normal foveolar epithelial samples stained positive for Lewis(b) antigen, whereas only 10.0% expressed Lewis(a) antigen. In contrast, intestinal metaplasia specimens had increased Lewis(a) antigen expression and slightly decreased Lewis(b) antigen expression. A similar pattern of Lewis(a) and Lewis(b) expression was observed in gastric adenomas and intestinal type adenocarcinomas. Lewis(x) and Lewis(y) were detected in all normal deep glands, but were not expressed in the majority of intestinal metaplasia specimens. In addition, only 20-40% of gastric adenomas and gastric carcinomas expressed Lewis(x) and Lewis(y) antigens. These changes in Lewis antigen expression in intestinal metaplasia, adenomas, and intestinal type adenocarcinomas suggest that altered expression of Lewis blood group-related antigens may correlate with cell transformation processes. PMID- 8503389 TI - Comparison of three methods to obtain upper small bowel contents for culture. AB - In this study of 27 patients with dyspepsia, we compared three methods for obtaining upper small bowel contents for culture: 1) the Enterotest or string capsule method, 2) duodenal intubation using a closed polyethylene tube filled with water that had been boiled for sterilization and removal of dissolved oxygen, and 3) brushing of duodenal mucosa with a cytology brush protected by a sheath (the last two done during endoscopy). In 12 of the 27 patients, duplicate intubations and brushings were performed. The samples obtained were cultured aerobically. Parameters used to compare the three methods were: the contribution of each method to the diagnosis of upper small bowel bacterial overgrowth (USBBO), agreement between the methods in diagnosis of USBBO and in detailed microbiological findings, and the reproducibility of diagnosis of USBBO and of microbiological findings in duplicate intubation and brushing. Intubation and brushing were highly reproducible and superior to the Enterotest in all of the tested parameters. Intubation and brushing are equally efficacious, but intubation is preferred because of the slight cost advantage, ease of specimen processing, and the ability to obtain anaerobic specimens. PMID- 8503390 TI - Fatal hyperphosphatemia following Fleet Phospo-Soda in a patient with colonic ileus. AB - A fatal case of hyperphosphatemia secondary to enteral administration of Fleet Phospo-Soda is presented. A 64-yr-old male admitted for theophylline toxicity was treated with activated charcoal and sorbitol, but subsequently developed colonic ileus. Two sequential doses of Phospo-Soda were administered to facilitate clearance of the charcoal; however, this resulted in marked hyperphosphatemia, hypocalcemia, acidemia, and other electrolyte abnormalities, followed by the patient's demise. This case is added to several other reports about the risks of injudicious use of sodium phosphate cathartics. PMID- 8503391 TI - Effect of cisapride on gastric emptying of indigestible solids and plasma motilin concentration in diabetic autonomic neuropathy. AB - To investigate the role of motilin in diabetic gastroparesis, we evaluated gastric emptying and plasma concentrations of motilin in diabetic patients. Gastric emptying of radiopaque marker was significantly delayed in the diabetics with autonomic neuropathy (n = 14) compared with the healthy controls (n = 6) (p < 0.01). Mean plasma motilin concentrations were significantly higher in the diabetics with autonomic neuropathy compared with the healthy controls (p < 0.01). A positive correlation was observed between gastric emptying and plasma motilin concentrations in the healthy controls (r = 0.955, p < 0.01), whereas these values were inversely correlated in the diabetics (r = 0.620, p < 0.01). Oral administration of cisapride (15 mg/day.14 day) significantly accelerated gastric emptying without an effect on plasma motilin concentration (p = 0.03). These observations suggest that gastric emptying in the diabetics with autonomic neuropathy is delayed despite elevated levels of motilin, and that cisapride accelerates gastric emptying, independent of the plasma motilin concentration. PMID- 8503392 TI - Massive bleeding from rectal varices. AB - An elderly female who experienced a life-threatening bleed from an isolated rectal varix is presented. She failed endoscopic injection sclerotherapy but responded to surgical ligation. The literature concerning well-documented bleeding from eight cases of rectal varices is reviewed. Nomenclature, diagnosis, and therapy are emphasized. PMID- 8503393 TI - Odynophagia caused by a pericardial diverticulum. AB - A 31-yr-old female presented with odynophagia and weight loss. Upper gastrointestinal endoscopy, esophageal manometry, and chest x-ray all were normal. However, computerized tomography of the chest revealed a mediastinal mass, which on mediastinoscopy proved to be a pericardial diverticulum. Surgical excision of this diverticulum resulted in complete resolution of her symptoms. This case report illustrates that mediastinal lesions should be considered as a potential cause of odynophagia when esophageal disease has been ruled out. PMID- 8503394 TI - Primary biliary cirrhosis associated with ulcerative colitis. AB - Hepatobiliary diseases are frequently associated with ulcerative colitis. The most commonly reported syndromes are primary sclerosing cholangitis, chronic active hepatitis and cirrhosis. Recently, the association of primary biliary cirrhosis and ulcerative colitis has been reported. We present a case of primary biliary cirrhosis in a young man with left-sided ulcerative colitis and review the previous reported cases, noting some unique similarities between them. PMID- 8503395 TI - Atypical arthropathy associated with Crohn's disease. AB - Inflammatory bowel disease may be associated with a variety of rheumatologic abnormalities. The patterns of described enteropathic arthritis, not associated with the HLA B27 antigen, include non-deforming peripheral arthritis, bilateral, symmetric sacroiliitis, an on occasion, destructive monoarthritis. We report three patients with Crohn's disease and patterns of joint disease that have not been previously described. The patients ranged in age from 16 to 31 yr. In all cases, both joint and bowel disease were present since childhood. Antinuclear antibody, rheumatoid factor, and HLA B27 antigen determinations were negative. The distribution and pattern of joint disease were similar to that seen in rheumatoid arthritis. We propose that these cases do not represent coincident rheumatoid arthritis and Crohn's disease, but, rather, atypical manifestations of enteropathic arthritis. PMID- 8503396 TI - Chronic recurrent esophageal strictures treated with balloon dilation in children with autosomal recessive epidermolysis bullosa dystrophica. AB - Two children (8- and 17-yr old) with autosomal recessive epidermolysis bullosa dystrophica and chronic esophageal strictures were treated with repeated balloon dilations. General anesthesia was by face mask adapted specifically for this procedure, with careful attention to avoid skin and mucus membrane damage. A balloon dilator positioned fluoroscopically over an angiographic guidewire was gently inflated until narrowings resolved. Dilations have been performed every 1 11 [4.3 +/- 3.2 (mean +/- SD)] months in the younger patient over the last 4.3 yr, and every 8-20 (14.5 +/- 5.9) months in the older patient over the last 4.8 yr, without serious complications. Both patients were able to swallow normal foods following dilations. Repeated balloon dilations of esophageal strictures in patients with epidermolysis bullosa dystrophica can be done safely. Further studies are indicated to determine its effectiveness and appropriateness as an alternative to colonic interposition. PMID- 8503397 TI - Delayed biliary drainage: help or hype? PMID- 8503398 TI - Luminal agents for invasive amebiasis: nice or necessary? PMID- 8503399 TI - Coffee and nonulcer dyspepsia. PMID- 8503400 TI - Use of disposable cytology brushes. PMID- 8503401 TI - CT-guided needle biopsy of the pancreas. PMID- 8503402 TI - Failure of percutaneous endoscopic gastrostomy insertion. PMID- 8503403 TI - Treatment of active Crohn's disease with an oral slow-release budesonide formulation. PMID- 8503404 TI - Another unusual guidewire complication in the common bile duct. PMID- 8503405 TI - Melanosis coli: a consequence of "alternative therapy" for psoriasis. PMID- 8503406 TI - Pharmacokinetics of famotidine in patients with liver cirrhosis. PMID- 8503407 TI - High prevalence of DRW10 and DQW1 antigens in celiac disease associated with recurrent aphthous stomatitis. PMID- 8503408 TI - Chemical irritational gastritis. PMID- 8503409 TI - Dysphagia in myotonic dystrophy. PMID- 8503410 TI - Dermoid cyst of the ileum. PMID- 8503411 TI - Lipoprotein metabolism and renal failure. AB - Lipoprotein metabolism is altered in the majority of patients with renal insufficiency and renal-failure, but may not necessarily lead to hyperlipidemia. The dyslipoproteinemia of renal disease has characteristic abnormalities of the apolipoprotein (apo) profile and lipoprotein composition. It develops during the asymptomatic stages of renal insufficiency and becomes more pronounced as renal failure advances. The qualitative characteristics of renal dyslipoproteinemia are not modified substantially by dialysis treatment. Patients with chronic renal disease may therefore be exposed to dyslipoproteinemia for long periods of time. The characteristic plasma lipid abnormality is a moderate hypertriglyceridemia. The alterations of lipoprotein metabolism affect both the apoB-containing very low-density and intermediate-density, and low-density lipoproteins and the apoA containing high-density lipoproteins. The main underlying abnormality of lipoprotein transport is a decreased catabolism of the apoB-containing lipoproteins caused by decreased activity of lipolytic enzymes and altered lipoprotein composition. There is an increase of intact or partially metabolized, triglyceride-rich, apoB-containing lipoproteins with a disproportionate elevation of apoC-III and, to a lesser extent, apoE, resulting in a marked increase of the intermediate-density lipoproteins and an enrichment of triglycerides, apoC-III, and apoE in the low-density lipoproteins. In high-density lipoproteins there are decreases in the concentrations of cholesterol, apolipoproteins A-I and A-II, and the high-density lipoprotein-2 to high-density lipoprotein-3 ratio. These abnormalities result in a characteristic decrease of the apoA-I to apoC-III ratio and anti-atherogenic index apoA-I/apoB. The pathophysiologic links between the renal insufficiency and the abnormalities of lipoprotein transport are still poorly defined. Changes in the action of insulin on lipolytic enzymes, possibly mediated via increased levels of parathyroid hormone, have been suggested to play a contributory role. The clinical consequences of a defective lipoprotein transport may be related to the atherogenic character of lipoprotein abnormalities. Renal dyslipoproteinemia may contribute to the development of atherosclerotic vascular disease and progression of glomerular and tubular lesions with subsequent deterioration of renal function. Dietary and/or pharmacologic intervention may ameliorate the uremic dyslipoproteinemia, but the long-term clinical effects of such treatment have yet to be established. PMID- 8503412 TI - Angiotensin II local hyperreactivity in the progression of IgA nephropathy. AB - Immunologic and hemodynamic factors are likely to work in synergism in the progression of immunoglobulin A nephropathy (IgAN) toward sclerosis. The local activation of the renin-angiotensin system may be one the most relevant mechanisms. We investigated the hemodynamic effects of the acute administration of angiotensin-converting enzyme inhibitor (ACEI) (captopril 50 mg). The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were measured by 51Cr-EDTA and 125I hippurate clearances. The correspondent filtration fractions (FFs) in basal conditions and after administration of ACEI were calculated, then the changes in FF (delta FF and % delta FF) were determined. We studied 27 IgAN patients. Eighteen patients had normal renal function (GFR, 112 +/- 19 mL/min/1.73 m2) and nine had moderate renal impairment (GFR, 54 +/- 13 mL/min/1.73 m2). Sixteen patients had proteinuria > or = 0.5 g/d. In addition, 12 glomerulonephritis control cases and eight healthy subjects were investigated. After the administration of ACEI in healthy subjects we observed slight modifications in the GFR, a significant increase in the ERPF (P < 0.005), and a significant decrease in FF (P < 0.04). Similarly, in IgAN patients with normal renal function the GFR increased slightly, the ERPF increased significantly (P < 0.01), and there was a decrease in FF (P < 0.01). The delta FF and % delta FF values were not significantly different from those found in the controls. In patients with initial renal failure GFR remained unchanged, ERPF increased significantly (P < 0.005), and FF significantly decreased (P < 0.004). However, the changes in delta FF and % delta FF were significantly greater than those found in healthy controls (P < 0.01) and in IgAN patients with normal renal function (P < 0.001). IgAN patients with proteinuria levels > or = 0.5 g/d showed greater changes in delta FF and % delta FF after the administration of ACEI than patients with proteinuria levels lower than 0.5 g/d (P < 0.003 and P < 0.04, respectively) or proteinuric control cases (P < 0.05 and P < 0.01, respectively). This different response in proteinuric and nonproteinuric patients was evident even when the analysis was limited to the subgroup of IgAN patients with normal renal function. The decrease in FF consequent to an increase in the ERPF after the administration of ACEI suggests a local hyperactivity of the renin angiotensin system in some cases of IgAN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8503413 TI - Renal function up to 50 years after unilateral nephrectomy in childhood. AB - Removal of one kidney during childhood differs from removal of a kidney from an adult as the child's future depends on an adequate function of the remaining kidney during a longer period of time. We assessed the long-term effect of unilateral nephrectomy in childhood on renal function, protein excretion, and blood pressure. Data were obtained from 111 subjects undergoing uninephrectomy for unilateral renal disease before the age of 16 years who had no evidence of renal abnormalities in the contralateral kidney at the time of surgery. At investigation the patients were 18 to 56 years of age with an interval of up to 52 years after uninephrectomy. On average, renal function was well maintained at approximately 75% of the reported normal two-kidney value. Blood pressure in men was higher than in women. Stratification for age showed no statistically significant differences between those undergoing uninephrectomy before or after the age of 4.5 years. Stratification for post-uninephrectomy interval revealed renal function to be lower and blood pressure, urinary albumin excretion, and protein excretion to be higher in those with an interval of more than 25 years. In men over 30 years of age, linear regression analysis indicated a decrease in glomerular filtration rate, effective renal plasma flow, and creatinine clearance, and an increase in blood pressure and albumin excretion with time. Controlled longitudinal studies are needed to detect true changes and to ascertain whether such changes are different from the age-related changes seen in individuals with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503414 TI - Effect of recombinant human erythropoietin on muscle energy metabolism in patients with end-stage renal disease: a 31P-nuclear magnetic resonance spectroscopic study. AB - To evaluate the effects of recombinant human erythropoietin (r-HuEPO) on muscle energy metabolism in patients with end-stage renal disease (ESRD), 10 patients receiving maintenance hemodialysis were given r-HuEPO (3,000 U three times a week for 8 weeks). Intracellular phosphocreatine to inorganic phosphate ratios and pH were measured with 31P-nuclear magnetic resonance spectroscopy before and after all-out handgrip exercise, before treatment and at 4 and 8 weeks after r-HuEPO treatment. The same measurements, from 14 normal individuals also were studied for comparison. The hematocrit increased significantly with r-HuEPO treatment, although the dose of r-HuEPO did not correct it to the normal level. The exercise capacity improved significantly. Intracellular pH was not different between the ESRD patients and controls or between before and after r-HuEPO treatment. The phosphocreatine to inorganic phosphate ratio at the resting state improved significantly with r-HuEPO treatment, reaching the same level as the normal subjects even before the low hematocrit normalized. The measurements immediately after exercise were the lowest levels obtained (the nadir state) and were not different between groups. In the state of maximum recovery, a pattern was noted that was similar to that found in the resting state. These results showed that r HuEPO treatment improved the phosphorylation potential during the resting state and the maximum phosphorylation potential during the postexercise recovery phase, and suggest that the treatment improved the rate of oxidative phosphorylation in ESRD patients receiving hemodialysis. PMID- 8503415 TI - Incidence, prevalence, and outcomes of end-stage renal disease patients placed in nursing homes. AB - We prospectively surveyed the 156 dialysis centers in Network 5 (MD, VA, WV, DC) for end-stage renal disease (ESRD) patients admitted to or begun on dialysis in nursing homes during a 21-month period (April 1, 1990 to December 31, 1991). In addition to this incidence data, information on patient demographics, social characteristics, pre-existent illnesses, and functional capacity (measured by activity of daily living [ADL] scores) was obtained. One hundred thirty-two centers (close to 90% of Network 5's approximately 9,000 patients) responded to the survey. Outcome data were gathered throughout the 21-month period and the subsequent 5 months. Seventy-three centers dialyzed 228 such patients during the 18-month period. Five centers that were located in the same building as a nursing home cared for 67 patients. The 228 patients, aged 17 to 101 years, were older (65.50 years +/- 14.2 [SD] v 53.7 +/- 16.4 years), and disproportionately female (62.2% v 48.3%), white (46.5% v 37.4%), and diabetic (57.9% v 29%) compared with the general network ESRD population (P < 0.05). On admission to the nursing home 47% of patients had organic heart disease, 35% had an organic brain syndrome, 22% had cerebrovascular diseases, 19% had amputations, and 18% were blind. The mean admission ADL score was 8.1 +/- 5.2 (maximum function, 18) and the patients did not differ regarding age, sex, race, or diabetes. Forty-three percent of patients lived alone or in sheltered housing before being placed in the nursing home.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503416 TI - Nephrologist-directed primary health care in chronic dialysis patients. AB - We previously found that chronic in-center hemodialysis patients relied on their nephrologists for the management of acute illnesses and comorbid chronic illnesses, such as diabetes mellitus and heart disease. Since chronic peritoneal dialysis differs from in-center hemodialysis, particularly in patients' exposure to nephrologists and other dialysis unit personnel, we asked chronic peritoneal dialysis patients about their reliance on nephrologists for general health care and compared their responses to those of in-center hemodialysis patients. A questionnaire consisting of patient demographic information and questions about primary medical care was completed by 118 chronic dialysis patients (74 in-center hemodialysis patients and 44 chronic peritoneal dialysis patients). Peritoneal dialysis patients were younger (mean age, 46 +/- 17 years v 56 +/- 17 years for hemodialysis patients, P < 0.005) and fewer had been on dialysis for more than 3 years (32% v 65%, P < 0.005). Seventy-one percent of all patients did not have a family physician (84 patients). More peritoneal dialysis patients had a family physician (43% v 20%, P < 0.025), but the proportion of hemodialysis and peritoneal dialysis patients who had seen their family physician within 6 months was similar (73% and 47%, respectively, P = 0.12). Most patients relied on their nephrologist for yearly physicals (80% of hemodialysis and 84% of peritoneal dialysis patients). More hemodialysis patients depended on nephrologists for the management of minor acute illnesses (91% v 64%, P < 0.005). At least 60% of chronic health problems were managed by the nephrologists and was not different among the two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503417 TI - Racial differences in the delivery of hemodialysis. AB - Differences in the quality of medical care provided to black and white patients have been observed in the United States, but have not been studied in dialysis patients. We examined whether dialysis delivery, as measured by indirect determination of Kt/V, differs between black and white patients in New Jersey. Five hundred forty-four patients at 10 New Jersey dialysis units were randomly selected by the US Health Care Financing Administration as part of their Medical Case Review Study. Of these, 237 patients at eight units were classified as black or white and had urea kinetic data available. The mean Kt/V urea was higher for white than black patients at all facilities, averaging 1.03 for the 123 black patients and 1.20 for the 114 white patients (P = 0.0006). Black patients were 40% more likely than white patients to have a Kt/V less than 1.0 (45.6% of black patients v 32.5% of white patients, P = 0.038). Racial disparities in dialysis delivery exist, the causes and consequences of which need to be addressed. PMID- 8503418 TI - Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. AB - The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (i.v.), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following i.v. Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following i.v. Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the i.v. dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 +/- 5.0 hours v 9.4 +/- 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0-96; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503419 TI - Beethoven's renal disease based on his autopsy: a case of papillary necrosis. AB - The autopsy report of Ludwig van Beethoven written by Dr Johann Wagner in 1827 reveals that he had renal calculi that had not been diagnosed during his lifetime, together with perirenal fibrosis. The most comprehensive interpretation of this autopsy finding is that the regular calcareous deposits in every one of his renal calices represented calcified necrotic papillae. Severe urinary obstruction or diabetes as possible causes of papillary necrosis were not present. Analgesic abuse because of headaches, back pain, and attacks of rheumatism or gout may be presumed on the basis of Beethoven's uncontrolled way of taking medication. Salicin, a commonly used analgesic substance of that time (dried and powdered willow bark), is able to cause papillary necrosis. Perirenal fibrosis may be due to chronic infection or drug intake. Beethoven's other well known diseases are deafness caused by otosclerosis of the inner ear, relapsing attacks of diarrhea as the symptoms of irritable bowel syndrome, and liver cirrhosis following viral hepatitis and chronic alcohol consumption. Liver cirrhosis also may cause papillary necrosis. In Beethoven's case, renal papillary necrosis was most probably the consequence of analgesic abuse together with decompensated liver cirrhosis. The autopsy report of Beethoven is the first case of papillary necrosis recorded in the literature. PMID- 8503420 TI - On the renal ailments of creators and leaders. PMID- 8503421 TI - Cholesterol crystal embolization-associated renal failure after therapy with recombinant tissue-type plasminogen activator. AB - We report the occurrence of renal failure due to cholesterol crystal embolization following thrombolytic therapy with intravenous recombinant tissue-type plasminogen activator (t-PA). No invasive vascular procedure had been performed. Although there is one case report of cholesterol crystal embolization following t PA therapy with only extrarenal manifestations (N Engl J Med 321:1270, 1989), this is the first reported case of atheroembolic acute renal failure following t PA therapy. PMID- 8503422 TI - Familial unilateral renal agenesis and focal and segmental glomerulosclerosis. AB - Renal dysplasia and agenesis may be a familial disorder. We report the familial occurrence of unilateral renal agenesis and proteinuria that, at least in one case, was related to focal glomerulosclerosis. Whether these abnormalities are related to an intrinsic abnormality in the remaining kidney, hyperfiltration injury, systemic hypertension, or some other poorly defined factor is unclear at present. However, this report, along with previous case reports of familial renal agenesis, suggests that ultrasonographic screening of first-degree relatives of patients with renal agenesis is appropriate. Whether treatments such as dietary protein restriction, use of angiotensin-converting enzyme inhibitors, or other therapeutic interventions will have a beneficial effect in asymptomatic individuals with unilateral renal agenesis remains to be determined. PMID- 8503423 TI - Naloxone-responsive encephalopathy in end-stage renal disease. AB - We report the case of a 61-year-old diabetic woman with end-stage renal disease who was on hemodialysis and who developed an encephalopathy and episodes of hypotension and hypoventilation, all of which showed rapid and dramatic responses on multiple occasions to the administration of the opiate antagonist naloxone. Improvement in encephalopathy was confirmed by electroencephalography. The patient had received no exogenous opiates and had a normal beta-endorphin level. She subsequently developed myoclonus and was treated for possible aluminum overload that was of borderline magnitude. We conclude that this patient had an encephalopathy that responded to opiate receptor blockade. Because of cerebrovascular disease, episodes of diminished blood pressure due to a state of increased opiate receptor stimulation may have unmasked this underlying encephalopathy. These effects may have been secondary to increased opiate-binding sites or to elevated central nervous system levels of endogenous opiates. PMID- 8503424 TI - Peritonitis due to Exophiala jeanselmei in a patient undergoing continuous ambulatory peritoneal dialysis. AB - We describe the second reported case of peritonitis caused by the fungus Exophiala jeanselmei in a patient on continuous ambulatory peritoneal dialysis (CAPD) and the first such patient to survive. Management of the patient consisted of Tenckhoff catheter removal and intravenous amphotericin B. PMID- 8503425 TI - Renal amyloidosis in systemic lupus erythematosus. PMID- 8503426 TI - Factors and guidelines to be considered in offering treatment to patients with end-stage renal disease: a personal opinion. PMID- 8503427 TI - Trust and the patient-physician relationship. PMID- 8503428 TI - Looking upon the water. Better committees than committors? PMID- 8503429 TI - What effect does blood pressure control have on the progression toward renal failure? AB - Since hypertension is associated with nephrosclerosis and an increased progression toward end-stage renal failure, the therapeutic approach to the treatment of hypertension should aim to protect the kidney against damage or to halt the progression toward end-stage renal failure. It appears that compared with systolic and mean blood pressure, the level of diastolic blood pressure is particularly associated with renal damage. In the presence of kidney failure the choice of antihypertensive drug should be made according to pharmacokinetic and pharmacodynamic properties. From the pharmacokinetic point of view, drugs that are eliminated via the biliary route are preferable since no dosage adjustment is required, and those with a favorable trough to peak effect can achieve better blood pressure control by reducing blood pressure variability. Pharmacodynamic properties should include efficacy in lowering blood pressure, beneficial renal effects, and good tolerability. Hence, the dihydropyridine calcium antagonists, which are effective during volume repletion and which counteract vasoconstrictor mechanisms, seem to be particularly effective. There is some suggestion, but no definitive proof, that blood pressure should be lowered well below 140/90 mm Hg; to achieve this, combination therapy frequently must be used. The rationale for combining two or more antihypertensive drugs is based on the knowledge that this combination can exert an additive antihypertensive action while reducing side effects. The combination of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist may well fulfill these criteria since this combination could enhance both antihypertensive and renal hemodynamic effects in comparison to single-drug treatment and could reduce the side effects of both drugs. PMID- 8503430 TI - Calcium antagonists and the kidney: future therapeutic perspectives. AB - During the past decade, attention has focused on the effects of calcium antagonists on renal function. Recent studies using diverse videomicroscopic techniques including the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that calcium antagonists acutely antagonize preglomerular vasoconstriction. In contrast, most studies suggest that the efferent arteriole appears to be refractory to the vasodilatory effects of these agents. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and, possibly, cyclosporine nephrotoxicity. Evidence has accrued to suggest that calcium antagonists also may be protective against acute radiocontrast-induced nephrotoxicity. Finally, the renal hemodynamic and natriuretic effects of calcium antagonists commend their use as antihypertensive agents in the management of essential hypertension and transplant-associated hypertension. PMID- 8503431 TI - Calcium antagonists and cellular mechanisms of glomerulosclerosis and atherosclerosis. AB - Glomerulosclerosis is the final common glomerular lesions in many renal diseases. The histological features of focal glomerulosclerosis resemble the lesion of atherosclerosis and may indicate a parallel pathogenesis. Central to the pathogenesis of atherosclerosis is the interaction of blood cells and endothelial cells with subsequent proliferation of smooth muscle cells and enhanced production of collagen. The mechanisms that appear to be responsible for this increased proliferative response are growth factors, cytokines, and local alterations in the extracellular matrix. The corresponding counterparts in glomerulosclerosis include mesangial expansion with mesangial cell proliferation, mesangial foam cell accumulation, tissue necrosis, and eventual sclerosis. Substances that interfere with the interaction between the different cell types, such as endothelial cells, macrophages, and platelets, and with the proliferative responses of both vascular and mesangial cells may be of therapeutic value in both diseases. Calcium antagonists interfere with the cellular activation induced by growth factors and vasoactive hormones and, in platelets, they decrease aggregation and the secretion of thromboxane from these cells. In addition to their relaxant effect, calcium antagonists diminish the proliferative response of vascular smooth muscle and mesangial cells to growth factors while, in macrophages, production of superoxides is decreased after incubation with calcium antagonists. In mesangial cells it has been demonstrated that calcium antagonists decrease the expression and secretion of matrix proteins. That these cellular mechanisms result in an anti-atherosclerotic effect in vivo has been shown by various animal studies, and a beneficial effect of calcium antagonists on the progression of glomerulosclerosis has also been observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503432 TI - Hypertension and the kidney--an overview. AB - The kidney plays a major role in the genesis of any type of hypertension, as demonstrated by experiments which show that hypertension can be "transplanted" when the kidney itself is transplanted. Hypertension is common in patients with renal disease, and may occur even at normal glomerular filtration rates. The mechanisms that promote hypertension and are involved in renal disease comprise both activation of pressor mechanisms and failure of depressor mechanisms, the latter having been considerably less well studied. The major pressor mechanisms are an abnormal pressure-natriuresis relationship and inappropriate activity of the renin-angiotensin system. PMID- 8503433 TI - Cytosolic calcium and insulin resistance. AB - The presence of insulin resistance in many patients with hypertension has become a well-recognized phenomenon. However, the mechanism of this association remains enigmatic. We have hypothesized that abnormal cellular calcium handling, particularly elevations in cytosolic free calcium concentrations, may represent a common intracellular abnormality (a missing link) that is responsible for the frequent co-existence of insulin resistance and hypertension. We have shown recently that sustained elevations of cytosolic free calcium in insulin target cells, such as are observed in patients with obesity and non-insulin-dependent diabetes mellitus and in some patients with hypertension, may lead to the development of insulin resistance. Although the mechanisms that lead to such increases are not yet well understood, they appear to include an enhanced influx of calcium via calcium channels. We found that the presence of the calcium antagonist nitrendipine in the incubation medium prevented increases in cytosolic free calcium concentration and ameliorated the insulin resistance induced by various mechanisms. To further evaluate the existence of an association between elevated levels of cytosolic calcium and diminished cellular sensitivity to insulin in patients with essential hypertension, we studied insulin sensitivity in vivo and in vitro in isolated adipocytes from older hypertensive, nondiabetic subjects. Obese hypertensive individuals demonstrated marked hyperinsulinemia and significantly reduced submaximally stimulated adipocyte 2-deoxyglucose uptake. One month of therapy with nitrendipine (10 mg twice daily) reduced blood pressure in hypertensive subjects, reduced plasma insulin to control values in obese hypertensive individuals, and restored adipocyte 2-deoxyglucose uptake at at submaximally effective insulin concentrations to control values in both obese hypertensive subjects and those of normal weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503434 TI - Vascular insulin abnormalities, hypertension, and accelerated atherosclerosis. AB - There is accumulating evidence that insulin resistance, glucose intolerance, and hyperinsulinemia exist in people with high blood pressure, and it has been suggested that insulin resistance and hyperinsulinemia may be of great importance in the origin of hypertension and its ultimate clinical course. Of importance are the recent observations that persons with normal glucose tolerance, selected on the basis of hyperinsulinemia, had higher blood pressure than matched individuals with normoinsulinemia. Hypertension in in insulin-resistant states generally has been attributed to hyperinsulinemia, with resulting increases in sympathetic nervous system activity. However, recent data from our laboratory suggest that cellular insulin resistance rather than hyperinsulinemia per se may lead to hypertension. The basic tenet proposed in this article is that a deficiency of insulin at the cellular level represents a common mechanism that is involved in the development of hypertension in both type I and type II diabetes mellitus. Insulin has an important role in the modulation of cellular calcium metabolism. Decreased insulin action on vascular smooth muscle cells may contribute both to hypertension and to accelerated atherosclerosis. Recent observations suggest that an impaired cellular response to insulin predisposes to increased vascular smooth muscle tone (the hallmark of hypertension in the diabetic state). For example, recently reported studies from our laboratory demonstrate that insulin attenuates the vascular contractile response to phenylephrine, serotonin, and potassium chloride. Thus, it appears that insulin normally modulates (attenuates) vascular smooth muscle contractile responses to vasoactive factors, and insulin resistance should accordingly be associated with enhanced vascular reactivity. PMID- 8503435 TI - Calcium antagonists and the diabetic hypertensive patient. AB - Roughly 40% of all diabetic patients, whether insulin dependent or not, develop persistent albuminuria (over 300 mg/24 hr), a decrease in the glomerular filtration rate, and elevated blood pressure, ie, diabetic nephropathy. Diabetic nephropathy is the single most important cause of end stage renal disease in the Western world, and accounts for over a quarter of all end stage renal disease. It also is a major cause of the increased morbidity and mortality seen in diabetic patients; for example, the cost of end stage renal care in the United States currently exceeds +1.8 billion per year for diabetic nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease. An impaired nocturnal decline in blood pressure is more prevalent in patients with diabetic nephropathy and autonomic neuropathy, and may contribute to the enhanced cardiovascular morbidity found in such patients. Moreover, raised blood pressure accelerates both the development and progression of diabetic nephropathy in insulin-dependent and non insulin-dependent diabetes. The relationship between arterial blood pressure and diabetic nephropathy thus seems to be a complex one: nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. Effective blood pressure reduction reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503436 TI - Nephroprotective effects of nitrendipine in hypertensive type I and type II diabetic patients. AB - Hypertension is significantly involved in the progression of diabetic nephropathy and in the development of end stage renal disease in both type I and type II diabetes mellitus. We have investigated whether long-term monotherapy with a calcium antagonist, nitrendipine, prevents the development of overt diabetic nephropathy in type I and type II diabetic patients with mild to moderate hypertension and persistent microalbuminuria (ie, incipient nephropathy). After a 4-week run-in and washout period, respectively, 25 patients met the inclusion criteria. Twenty-two patients (six with type I and 16 with type II diabetes) completed the 12-month study. Twelve months of treatment with nitrendipine resulted in a significant reduction in systolic blood pressure in patients with type I (157.5 +/- 8.1 mm Hg v 135.8 +/- 4.2 mm Hg, P < 0.05) and type II (163.1 +/- 4.3 mm Hg v 135.9 +/- 3.6 mm Hg, P < 0.001) diabetes. A significant reduction also was seen in diastolic blood pressure (91.7 +/- 1.7 mm Hg v 79.2 +/- 3.5 mm Hg in type I diabetic patients, P < 0.01; 94.7 +/- 1.4 mm Hg v 78.1 +/- 1.5 mm Hg in type II diabetic patients, P < 0.001). A significant reduction in albuminuria was associated with the blood pressure reduction in both type I (57.8 +/- 11.9 mg/24 hr v 24.9 +/- 5.9 mg/24 hr, -57%) and type II (134.6 +/- 20.7 mg/24 hr v 70.3 +/- 16.8 mg/24 hr, -48%) diabetic patients. The mean glomerular filtration rate increased by 21% (112 +/- 12 mL/min v 135 +/- 14 mL/min) and by 23% (106 +/- 12 mL/min v 130 +/- 14 mL/min) in type I and type II diabetic patients, respectively. No significant changes were found in renal plasma flow rates or in serum concentrations of beta 2-microglobulin. With the exception of a significant (P < 0.05) reduction in hemoglobin A1 concentration in type II diabetic patients after 3 months of treatment with nitrendipine, fasting blood glucose, hemoglobin A1, residual beta-cell function (C-peptide levels), total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index remained essentially unchanged during follow up. These findings suggest that 12 months of monotherapy with the dihydropyridine type calcium antagonist nitrendipine reduced albuminuria and increased the lowered glomerular filtration rate without adverse effects on glucose and lipid control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8503437 TI - X-linked mental retardation: in pursuit of a gene map. PMID- 8503438 TI - X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. AB - We have identified a large Dutch kindred with a new form of X-linked nondysmorphic mild mental retardation. All affected males in this family show very characteristic abnormal behavior, in particular aggressive and sometimes violent behavior. Other types of impulsive behavior include arson, attempted rape, and exhibitionism. Attempted suicide has been reported in a single case. The locus for this disorder could be assigned to the Xp11-21 interval between DXS7 and DXS77 by linkage analysis using markers spanning the X chromosome. A maximal multipoint lod score of 3.69 was obtained at the monoamine oxidase type A (MAOA) locus in Xp11.23-11.4. Results of 24-h urine analysis in three affected males indicated a marked disturbance of monoamine metabolism. These data are compatible with a primary defect in the structural gene for MAOA and/or monoamine oxidase type B (MAOB). Normal platelet MAOB activity suggests that the unusual behavior pattern in this family may be caused by isolated MAOA deficiency. PMID- 8503439 TI - The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21). AB - Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here we report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at theta = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes that have hypogonadism and hypogenitalism and that previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women. PMID- 8503440 TI - Linkage mapping of a severe X-linked mental retardation syndrome. AB - A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26. PMID- 8503441 TI - Characterization of de novo duplications in eight patients by using fluorescence in situ hybridization with chromosome-specific DNA libraries. AB - Fluorescence in situ hybridization (FISH) with chromosome-specific DNA libraries was performed on samples from eight patients with de novo chromosomal duplications. In five cases, the clinical phenotype and/or cytogenetic evaluations suggested a likely origin of the duplicated material. In the remaining three cases, careful examination of the GTG-banding pattern indicated multiple possible origins; hybridization with more than one chromosome-specific library was performed on two of these cases. In all cases, FISH conclusively identified the chromosomal origin of the duplicated material. In addition, the hybridization pattern was useful in quantitatively delineating the duplication in two cases. PMID- 8503442 TI - The haplotype-relative-risk (HRR) method for analysis of association in nuclear families. AB - One major problem in studying an association between a marker locus and a disease is the selection of an appropriate group of controls. However, this problem of population stratification can be circumvented in a quite elegant manner by family based methods. The haplotype-relative-risk (HRR) method, which samples nuclear families with a single affected child and uses the parental haplotypes not transmitted to that child as a control individual, represents such a method for estimating the relative risk of a marker phenotype. In the special case of a recessive disease, it was already known that the equivalence of the HRR method with the classical relative risk (RR) obtained from independent samples holds only if the probability theta of a recombination between marker and disease locus is zero. We extend this result to an arbitrary mode of inheritance. Furthermore, we compare the distribution of the estimators for HRR and RR and show that, in the case of a positive linkage disequilibrium between a marker and disease allele, the distribution of the estimator for HRR is (stochastically) smaller than that for RR, irrespective of the recombination fraction. The practical implication of this result is that, for the HRR method, there is no tendency to give unduly high risk estimators, even for theta > 0. Finally, we give an expression for the standard error of the estimator for HRR by taking into account the nonindependence of transmitted and nontransmitted parental marker alleles in the case of theta > 0. PMID- 8503443 TI - Phenotype/genotype correlations in Gaucher disease type I: clinical and therapeutic implications. AB - Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. Highly statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370S/? genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. PMID- 8503444 TI - Incorrect specification of marker allele frequencies: effects on linkage analysis. AB - Most current linkage analyses make use of highly polymorphic DNA markers. Assigning correct allele frequencies for these markers may be extremely difficult in particular study populations. Designation of erroneous frequencies may result in false-positive evidence for linkage, as well as in failure to correctly exclude linkage. These effects are most pronounced in small pedigrees with key individuals unavailable for typing. The power to correctly detect true linkage does not appear to be greatly affected by inaccurate allele frequencies. Before linkage analyses are performed for specific pedigrees, it is recommended that simulation analyses be performed, followed by uncertainty and sensitivity analyses. PMID- 8503445 TI - Estimation of the incidence of a rare genetic disease through a two-tier mutation survey. AB - Recent attempts to detect mutations involving single base changes or small deletions that are specific to genetic diseases provide an opportunity to develop a two-tier mutation-screening program through which incidence of rare genetic disorders and gene carriers may be precisely estimated. A two-tier survey consists of mutation screening in a sample of patients with specific genetic disorders and in a second sample of newborns from the same population in which mutation frequency is evaluated. We provide the statistical basis for evaluating the incidence of affected and gene carriers in such two-tier mutation-screening surveys, from which the precision of the estimates is derived. Sample-size requirements of such two-tier mutation-screening surveys are evaluated. Considering examples of cystic fibrosis (CF) and medium-chain acyl-CoA dehydrogenase deficiency (MCAD), the two most frequent autosomal recessive disease in Caucasian populations and the two most frequent mutations (delta F508 and G985) that occur on these disease allele-bearing chromosomes, we show that, with 50-100 patients and a 20-fold larger sample of newborns screened for these mutations, the incidence of such diseases and their gene carriers in a population may be quite reliably estimated. The theory developed here is also applicable to rare autosomal dominant diseases for which disease-specific mutations are found. PMID- 8503446 TI - Molecular studies of trisomy 18. AB - We have determined the parental origin of 50 cases of trisomy 18. In 48 cases the additional chromosome was maternal in origin, and in 2 cases it was paternal in origin. Seven cases, including both those with an additional paternal chromosome, appeared to be the result of postzygotic error. In contrast to the situation in nondisjunction involving chromosomes 21 and X, there was no evidence for nullochiasmate nondisjunction. PMID- 8503447 TI - Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13;14) trisomy 14. AB - Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. We recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hypercholesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, we have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14. There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed--and subsequent cytogenetic analysis confirmed--that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a "maternal UPD chromosome 14 syndrome" is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes. PMID- 8503448 TI - Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. AB - A clinical and molecular analysis of 439 individuals affected with myotonic dystrophy, from 101 kindreds, has shown that the size of the unstable CTG repeat detected in nearly all cases of myotonic dystrophy is related both to age at onset of the disorder and to the severity of the phenotype. The largest repeat sizes (1.5-6.0 kb) are seen in patients with congenital myotonic dystrophy, while the minimally affected patients have repeat sizes of < 0.5 kb. Comparison of parent-child pairs has shown that most offspring have an earlier age at onset and a larger repeat size than their parents, with only 4 of 182 showing a definite decrease in repeat size, accompanied by a later age at onset or less severe phenotype. Increase in repeat size from parent to child is similar for both paternal and maternal transmissions when the increase is expressed as a proportion of the parental repeat size. Analysis of congenitally affected cases shows not only that they have, on average, the largest repeat sizes but also that their mothers have larger mean repeat sizes, supporting previous suggestions that a maternal effect is involved in the pathogenesis of this form of the disorder. PMID- 8503450 TI - "Cryptic" repeating triplets of purines and pyrimidines (cRRY(i)) are frequent and polymorphic: analysis of coding cRRY(i) in the proopiomelanocortin (POMC) and TATA-binding protein (TBP) genes. AB - Triplets of the form of purine, purine, pyrimidine (RRY(i)) are enhanced in frequency in the genomes of primates, rodents, and bacteria. Some RRY(i) are "cryptic" repeats (cRRY(i)) in which no one tandem run of a trinucleotide predominates. A search of human GenBank sequence revealed that the sequences of cRRY(i) are highly nonrandom. Three randomly chosen human cRRY(i) were sequenced in search of polymorphic alleles. Multiple polymorphic alleles were found in cRRY(i) in the coding regions of the genes for proopiomelanocortin (POMC) and TATA-binding protein (TBP). The highly polymorphic TBP cRRY(i) was characterized in detail. Direct sequencing of 157 unrelated human alleles demonstrated the presence of 20 different alleles which resulted in 29-40 consecutive glutamines in the amino-terminal region of TBP. These alleles are differentially distributed among the races. PCR was used to screen 1,846 additional alleles in order to characterize more fully the range of variation in the population. Three additional alleles were discovered, but there was no example of a substantial sequence amplification as is seen in the repeat sequences associated with X linked spinal and bulbar muscular atrophy, myotonic dystrophy, or the fragile-X syndrome. The structure of the TBP cRRY(i) is conserved in the five monkey species examined. In the chimpanzee, examination of four individuals revealed that the cRRY(i) was highly polymorphic, but the pattern of polymorphism differed from that in humans. The TBP cRRY(i) displays both similarities with and differences from the previously described RRY(i) in the coding sequence of the androgen receptor. Our data suggest how simple tandem repeats could evolve from cryptic repeats. PMID- 8503449 TI - Negative expansion of the myotonic dystrophy unstable sequence. AB - We have analyzed the unstable fragment of the myotonic dystrophy (DM) gene in a pregnancy at 50% risk for DM. The affected father in this family had a 3.0-kb expansion of the DM unstable region. The fetus inherited the mutated gene, but with an expansion of 0.5 kb. This case represented a counseling problem in light of the absence of data concerning "negative expansion." Analysis of the DM gene in 17 families with 72 affected individuals revealed four more cases of negative expansions, all of them in paternal transmissions. The possible significance of this finding is discussed. PMID- 8503451 TI - Analysis of four microsatellite markers on the long arm of chromosome 9 by meiotic recombination in flow-sorted single sperm. AB - Meiotic recombination in flow-sorted single sperm was used to analyze four highly polymorphic microsatellite markers on the long arm of chromosome 9. The microsatellites comprised three tightly linked markers: 9CMP1 (D9S109), 9CMP2 (D9S127), and D9S53, which map to 9q31, and a reference marker, ASS, which is located in 9q34.1. Haplotypes of single sperm were assessed by using PCR in a single-step multiplex reaction to amplify each locus. Recombinant haplotypes were identified by their relative infrequency and were analyzed using THREELOC, a maximum-likelihood-analysis program, and an adaptation of CRI-MAP. The most likely order of these markers was cen-D9S109-D9S127-D9S53-ASS-tel with D9S109, D9S127, and D9S53 being separated by a genetic distance of approximately 3%. The order of the latter three markers did not however achieve statistical significance using the THREELOC program. PMID- 8503452 TI - A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance. AB - Manic-depressive illness (MDI), also known as "bipolar affective disorder," is a common and devastating neuropsychiatric illness. Although pivotal biochemical alterations underlying the disease are unknown, results of family, twin, and adoption studies consistently implicate genetic transmission in the pathogenesis of MDI. In order to carry out linkage analysis, we ascertained eight moderately sized pedigrees containing multiple cases of the disease. For a four-allele marker mapping 5 cM from the disease gene, the pedigree sample has > 97% power to detect a dominant allele under genetic homogeneity and has > 73% power under 20% heterogeneity. To date, the eight pedigrees have been genotyped with 328 polymorphic DNA loci throughout the genome. When autosomal dominant inheritance was assumed, 273 DNA markers gave lod scores < -2.0 at recombination fraction (theta) = .0, 174 DNA loci produced lod scores < -2.0 at theta = .05, and 4 DNA marker loci yielded lod scores > 1 (chromosome 5--D5S39, D5S43, and D5S62; chromosome 11--D11S85). Of the markers giving lod scores > 1, only D5S62 continued to show evidence for linkage when the affected-pedigree-member method was used. The D5S62 locus maps to distal 5q, a region containing neurotransmitter receptor genes for dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid. Although additional work in this region may be warranted, our linkage results should be interpreted as preliminary data, as 68 unaffected individuals are not past the age of risk. PMID- 8503453 TI - The genetic background of individual variations of circadian-rhythm periods in healthy human adults. AB - As a group phenomenon, human variables exhibit a rhythm with a period (tau) equal to 24 h. However, healthy human adults may differ from one another with regard to the persistence of the 24-h periods of a set of variables' rhythms within a given individual. Such an internal desynchronization (or individual circadian dyschronism) was documented during isolation experiments without time cues, both in the present study involving 78 male shift workers and in 20 males and 19 females living in a natural setting. Circadian rhythms of sleep-wake cycles, oral temperature, grip strength of both hands, and heart rate were recorded, and power spectra analyses of individual time series of about 15 days were used to quantify the rhythm period of each variable. The period of the sleep-wake cycle seldom differed from 24 h, while rhythm periods of the other variables exhibited a trimodal distribution (tau = 24 h, tau > 24 h, tau < 24 h). Among the temperature rhythm periods which were either < 24 h or > 24 h, none was detected between 23.2 and 24 h or between 24 and 24.8 h. Furthermore, the deviations from the 24-h period were predominantly grouped in multiples of +/- 0.8 h. Similar results were obtained when the rhythm periods of hand grip strength were analyzed (for each hand separately). In addition, the distribution of grip strength rhythm periods of the left hand exhibited a gender-related difference. These results suggested the presence of genetically controlled variability. Consequently, the distribution pattern of the periods was analyzed to elucidate its compatibility with a genetic control consisting of either a two-allele system, a multiple allele system, or a polygenic system. The analysis resulted in structuring a model which integrates the function of a constitutive (essential) gene which produces the exact 24-h period (the Dian domain) with a set of (inducible) polygenes, the alleles of which, contribute identical time entities to the period. The time entities which affected the rhythm periods of the variables examined were in the magnitude of +/- 0.8 h. Such an assembly of genes may create periods ranging from 20 to 28 h (the Circadian domain). The model was termed by us "The Dian-Circadian Model." This model can also be used to explain the beat phenomena in biological rhythms, the presence of 7-d and 30-d periods, and interindividual differences in sensitivity of rhythm characteristics (phase shifts, synchronization, etc.) to external (and environmental) factors. PMID- 8503455 TI - Genetic-counseling implications for cleft lip if an autosomal recessive major locus accounts for all cases. PMID- 8503454 TI - Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. AB - Triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketolisomerase [E.C.5.3.1.1]) deficiency is an autosomal recessive disorder that typically results in chronic, nonspherocytic hemolytic anemia and in neuromuscular impairment. The molecular basis of this disease was analyzed for one Hungarian family and for two Australian families by localizing the defects in TPI cDNA and by determining how each defect affects TPI gene expression. The Hungarian family is noteworthy in having the first reported case of an individual, A. Jo., who harbors two defective TPI alleles but who does not manifest neuromuscular disabilities. This family was characterized by two mutations that have never been described. One is a missense mutation within codon 240 (TTC [Phe]-->CTC [Leu]), which creates a thermolabile protein, as indicated by the results of enzyme activity assays using cell extracts. This substitution, which changes a phylogenetically conserved amino acid, may affect enzyme activity by disrupting intersubunit contacts or substrate binding, as deduced from enzyme structural studies. The other mutation has yet to be localized but reduces the abundance of TPI mRNA 10-20-fold. Each of the Australian families was characterized by a previously described mutation within codon 104 (GAG [Glu]-->GAC [Asp]), which also results in thermolabile protein. PMID- 8503456 TI - Identical SRY mutations with different phenotypic effects. PMID- 8503457 TI - Sensitivity of single-strand conformation polymorphism (SSCP) analysis in detecting p53 point mutations in tumors with mixed cell populations. PMID- 8503458 TI - Reanalysis of Hanford data: 1944-1986 deaths. AB - Reanalysis of Hanford data by a method, which is new only in the sense that it makes new uses of standard epidemiological procedures, has produced evidence of a cancer risk at low dose levels. By a conservative estimate, about three per cent of the pre-1987 cancer deaths of Hanford workers had occupational exposures to external radiation as the critical (induction) event. These radiogenic cancers were evenly distributed between five diagnostic groups, but as a result of there being much greater sensitivity to "cancer induction by radiation" after, rather than before, 50 years of age, they were concentrated among the cancers which proved fatal after 70 years of age. The reanalysis provides no support for the idea that radiation is more likely to cause leukemia than solid tumors, or the idea that there is reduced cancer effectiveness of radiation at low dose levels (dose rate effectiveness factor or DREF hypothesis), but the estimated proportion of radiogenic cancers was much higher for the 175 nonfatal cancers (which had other certified causes of death) than for the 1,732 fatal cases. Finally, according to the latest publication of the US Committee on Biological Effects of Ionizing Radiation (BEIR V), dose rate is more important than exposure age, and even a single exposure to 10 rem would only increase the normal cancer risk by four percent. Nevertheless, for all recorded exposures of Hanford workers, the estimated doubling dose was close to 26 rem; for exposures after 58 years, it was close to 5 rem, and for exposures after 62 years, it was less than 1 rem. PMID- 8503459 TI - Transport injuries in small coal mines: an exploratory analysis. AB - Mine Safety and Health Administration (MSHA) surveillance data were analyzed to elucidate mine characteristics or injury characteristics that distinguished mines with high rates of transport-related injuries from mines with lower transport injury rates. The results showed that most high-rate mines are small, high-rate mines have a disproportionate number of injuries involving young and less experienced workers, and injuries in high-rate mines are proportionally more severe. Further analyses of the MSHA injury data showed that smaller mines have a greater share of fatal and permanently disabling injuries, whereas larger mines have a greater share of injuries involving no lost time. Based on these results, we explored two explanations for the small mine injury risk: (1) a suggestion that differences in injury reporting between large and small mines may contribute to an apparent small mine injury risk, and (2) identification of factors contributing to a true difference in transport-related injury risk between small and large mines. Whereas it was true that most high injury rate mines were small, most small mines were actually zero-rate, having reported employment but no injuries to MSHA. An analysis employing binomial probability theory showed that a substantial proportion of small mines reported zero injuries when it was statistically probable that injuries would have occurred. This indicated that small mines may underreport injuries relative to larger mines. The possibility that reporting bias affected the associations found in this study was explored by eliminating the least severe injuries from the data set and evaluating changes in associations. This "adjustment" for reporting bias did not change previously observed relationships. Finally, MSHA injury data were analyzed in concert with mining population data collected by the Bureau of Mines. With such denominator information, the results indicated a disproportionately high risk of injury among workers in their first year at a mine and indicated that higher injury risk in small mines might be explained by the fact that workers at small mines have substantially less experience than workers at large mines. An effect of age was not found in these analyses. These results suggest the potential importance of targeted training programs for newly hired miners. Results also point to the need to explore specific factors contributing to the small mine injury risk, and to the necessity for complete and accurate reporting of injury data. PMID- 8503460 TI - Acute traumatic injuries in underground bituminous coal miners. AB - Using injury information from the 1986 Mine Safety and Health Administration database, and demographic information from a 1986 sample survey of the miner population, acute traumatic injury rates for male workers in underground bituminous coal mines were computed by age, current job experience, and total mine work experience. Three groups of workers assessed in this study showed the highest injury rates: workers aged 15-30 years; workers with between 2 and 3 years of experience; and workers with 10 or more years of experience in the current job. Injury rates decline with age in each time-interval of current job category and each total mine working experience category. Experience per se does not appear to be related to lower injury rates independent of age, which is paradoxical. The interaction of worker age with length of current or total mining experience is complex. The potential for catastrophic multiple fatalities and severe injuries suggests that additional work is needed to study, simultaneously, factors such as training and job task, and those that describe specific work exposures and mining hazards. PMID- 8503462 TI - An evaluation of New Jersey's hospital discharge database for surveillance of severe occupational injuries. AB - Computerized population-based hospital discharge data in New Jersey offer new opportunities for surveillance of serious work-related injuries. This database was evaluated for its potential in identifying selected injuries that occurred at work during 1985 and 1986. Hospital discharge data were compared with data collected by telephone interview of discharged patients. A total of 1,575 unique hospital discharge records for the selected injuries included finger amputation (1,041), thumb amputation (209), crush injury of the lower limb (208), toxic effects of heavy metals (69), and eye burns (48). Of 809 study subjects sent letters, 445 (55%) could be contacted and 289 (36%) were interviewed for the study. Sixty-one percent (175) said their injury was work related. A comparison was made between self-reported injury at work, and the presence of workers' compensation payer codes on the discharge database. The agreement beyond chance (Kappa) was 0.78 (95% CI = 0.67, 0.89). The sensitivity of this indicator of work relatedness was 83%; specificity was 98%. These data suggest that workers' compensation payment on the hospital discharge database may be a good to excellent proxy indicator of the work relatedness of these injuries. However, this proxy indicator will underestimate the number of work-related injuries by about 20%. Only 11% of hospital discharge records had external cause of injury codes (E-codes), which reduces the utility of the database for understanding the causal mechanisms of work-related injuries. PMID- 8503461 TI - Risk of hospitalization for specific non-work-related conditions among laborers and their families. AB - To better describe patterns of nonoccupational morbidity among construction laborers and their dependents, two health insurance plans organized by local unions of the Laborers' International Union of North America provided their medical claims data for 1989. The observed numbers of hospital admissions were compared with the numbers expected, based on the age-sex-specific hospital discharge rates from the 1989 National Hospital Discharge Survey. Standardized morbidity ratios thus obtained showed excesses for alcohol and drug dependence, complications related to pregnancy, and several other conditions. Medical claims data are a very useful resource in epidemiologic and medical care research, but their use poses numerous challenges, mainly related to the accuracy of diagnostic recording, problems in comparing different health insurance plans, and confounding factors due to health insurance largely being a condition of employment. Nevertheless, the use of these data can provide specific hypotheses for further study. PMID- 8503463 TI - Hospitalized occupational finger amputations, New Jersey, 1985 and 1986. AB - About 19,000 finger amputations occur at work each year in the United States. Twenty percent of these injuries are severe enough to require hospitalization. Hospital discharge data from New Jersey (1985, 1986) were used to describe the demographic characteristics of persons with such injuries and to identify potential subjects for telephone interview. A total of 637 persons hospitalized for finger amputations were sent letters asking for their participation. Of 637 persons, 355 (56%) were contacted and 228 (36%) were interviewed, of whom 134 (59%) said their injury occurred at work. The annual rate of finger amputations at work was 9.3 per 100,000 employed persons. The rate was higher for males (14.7) than females (1.9). The age-adjusted rates were higher for Hispanic (52.8) and black (28.9) males than for white males (9.5). Persons working with machines or maintaining them in the manufacturing industry were at highest risk. Unjamming or repairing machinery (e.g., presses, saws, or slicers) while in operation was particularly hazardous. These data can be used to target occupations and industries for specific worksite intervention to prevent finger amputations. One limitation of this study, however, is that hospitalized occupational finger amputations may not be representative of all finger amputations, the majority of which are less severe and do not require hospitalization. PMID- 8503464 TI - Use of organic solvents and potential worker exposure in the motor vehicle manufacturing industry. AB - This survey was designed to assist with planning epidemiologic studies of the effects of solvent exposure among motor vehicle manufacturing workers. The objectives were to identify subgroups of workers with solvent exposure, and to evaluate the availability of data for a job-exposure matrix (JEM). Of 65 plants selected, 31 (48%) participated. Participant plants represent all production activities initially included in the survey, and employ 97,655 hourly workers. About 14% of these workers use organic solvents (direct exposure), and 19% work in the proximity of solvent-using operations (indirect exposure). However, only 3% have direct exposure, and 6% have indirect exposure to large-volume (> or = 100 gallons/month)/high-frequency (hourly)-use solvents. The highest solvent exposure prevalence occurs in plants manufacturing engines and power train components and in metal degreasing/cleaning and painting tasks, and entails exposure to petroleum fractions, aromatic hydrocarbons, alcohols, and ketones. A JEM can be developed using plant records on job titles, work histories, production scheduling, and plant engineering, and using the corporate computerized personnel and industrial hygiene databases. However, information on solvent use and on exposure is adequate only for recent time periods. PMID- 8503465 TI - The utility of health education among lead workers: the experience of one program. AB - Health education represents a fundamental tool in the prevention of occupational diseases. For lead-exposed workers, work practices, personal hygiene, and life habits are certainly influences in the amount of the metal absorbed in the body. This study evaluated the effectiveness of a health education program in 50 workers exposed to inorganic lead employed in seven small factories. The study was performed in 3 phases over one year. Before the program, blood lead levels were measured, and a questionnaire was administered in order to evaluate the baseline knowledge of the workers about lead poisoning and its prevention. After the health education program, the blood lead levels decreased (from 38.2 to 32.3 micrograms/dl) and the questionnaire scores improved in a highly significant manner (p < 0.001). These results were obtained both in the short (4 months) and in the medium term (1 year). The reduction of blood lead concentrations seemed to be due to changes in hygienic behaviors and life habits, such as alcohol consumption or cigarette smoking, probably induced by an increase in specific knowledge about the prevention of lead damages. PMID- 8503466 TI - Investigation of an outbreak of "humidifier fever" in a print shop. AB - An outbreak of "humidifier fever" affected 16 (57%) of 28 workers in a print shop. The most common symptoms were myalgia, chills or subjective fever, and cough. Illness began 5-13 hours after entering the workplace, and lasted 2-24 hours. A humidifier in use the day of the outbreak was found to be contaminated with fungi, amebae, and Gram-negative bacteria. The risk of illness was highest for those who had been on the job 3 months before the outbreak, a time when the humidifier was in constant use. Serologic studies of print shop workers showed positive reactions to extracts of organisms isolated from the humidifier, but could neither distinguish ill from well workers, nor identify causative organisms. The presence of endotoxin-producing bacteria and the clinical syndrome are consistent with an organic dust toxic syndrome. Previous exposure appeared to be the major risk factor for illness. PMID- 8503467 TI - Methodology and utility of a job-exposure matrix. AB - We have previously reported a study in which a job-exposure matrix was applied to census data, identifying, e.g., polychlorinated biphenyls (PCBs) and creosote as increasing the risk of urothelial cancer. In this article, we expand on some theoretical issues, and present detailed accounts of constructed linkages for PCBs, creosote, and phenols. For agents of interest, one should emphasize the positive predictive value rather than the sensitivity in the construction of the matrix. The reverse is true for confounding factors; to avoid residual confounding after restriction to subjects unexposed for the confounding factors, one should emphasize sensitivity, possibly compromising the positive predictive value. This discrepancy between agents of interest and confounding factors may limit the application of a general matrix for studying several different diseases. The construction of the matrix is much harder, if sensitivity rather than positive predictive value is emphasized for an agent. Confounding from industry-related agents arises due to a true mixed exposure in certain work tasks, but also due to a gross classification of occupations in the census. One should not confuse different levels of the positive predictive value with exposure dose. A "dose-response" with different levels of positive predictive value reflects an accuracy of the matrix, not a biological phenomenon. Studies with exposure information from a job-exposure matrix applied to registers with scant information on occupation and industry may be warranted for exposures and diseases for which previous studies with a detailed documentation of exposure have low precision. PMID- 8503468 TI - Re: Attitudes and opinions regarding asbestos and cancer, 1934-1965. PMID- 8503469 TI - Re: Attitudes and opinions regarding asbestos and cancer, 1934-1965. PMID- 8503471 TI - Re: Historical reasons for attitudes and opinions regarding asbestos and cancer, 1934-1965. PMID- 8503470 TI - Re: Attitudes and opinions regarding asbestos and cancer, 1934-1965. PMID- 8503472 TI - Re: "Changing attitudes and opinions regarding asbestos and cancer, 1934-1965". PMID- 8503473 TI - Re: Asbestos and cancer, 1934-1965. PMID- 8503475 TI - Clinical management of the depressed geriatric patient: current therapeutic options. AB - Depression is probably the most common psychiatric illness affecting the elderly. Although depression in the elderly usually responds to treatment, it often goes unrecognized and, left untreated, may lead to considerable morbidity and mortality. Reversible causes of depression (e.g., medications; infectious states; endocrine, collagen, neurologic, and neoplastic disorders; and nutritional deficiencies) must all be ruled out before instituting therapy. Psychotherapy, electroconvulsive therapy (ECT), and pharmacologic therapy are the main therapeutic approaches used to manage depression. The pharmacologic options- tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, aminoketones, and triazolopyridines--each appear to be efficacious; however, the side-effect profile of some of the agents makes them more appropriate for use in elderly patients. It is imperative for clinicians, when choosing therapy for elderly depressed patients, to keep firmly in mind all risks, as well as benefits, inherent in each choice. PMID- 8503474 TI - Considerations of specificity in assessing the relationship between asbestos and cancer. PMID- 8503476 TI - Depression and increased risk of mortality in the nursing home patient. AB - Depression is a common clinical syndrome in the elderly, often resulting in attempted and/or successful suicide. Within the community and in a wide range of medical care settings, including nursing homes, depression is often undiagnosed and untreated. In a 1-year investigation that included 454 new patient admissions to eight Baltimore area nursing home facilities, major depressive disorder occurred in 12.6% of patients; an additional 18.1% had depressive symptoms. Most cases of depression were unrecognized and therefore untreated by nursing home physicians. Major depressive disorder was found to be an independent risk factor for mortality that increased the likelihood of death by 59% in the first year after diagnosis. Because new federal regulations now mandate the assessment of depression in nursing home patients, improved diagnosis and therapy (and therefore reduced disability and mortality) may be expected in the future. PMID- 8503477 TI - Recent pharmacologic advances in antidepressant therapy for the elderly. AB - Major depression is a common, serious, and potentially life-threatening illness in the elderly. Moreover, this population is perhaps the most difficult to treat effectively and safely for this disease. Changes in physiology associated with advancing age produce clinically significant differences in drug metabolism and pharmacokinetics in these patients versus younger individuals. The elderly are also more likely than young patients to receive treatment for multiple illnesses. This fact increases the potential for serious pharmacodynamic and pharmacokinetic drug-drug interactions. The practicing clinician now has five distinct classes of antidepressant medications that may be used for treating depression in the elderly: tricyclic antidepressants (TCAs; e.g., desipramine, nortriptyline), monoamine oxidase inhibitors (MAOIs; e.g., isocarboxazid, tranylcypromine), selective serotonin reuptake inhibitors (SSRIs; i.e., fluoxetine, sertraline, and paroxetine), aminoketones (i.e., bupropion), and triazolopyridines (i.e., trazodone). Although all are effective antidepressants, the SSRI class may be the best choice for the treatment of elderly depressed patients, based on a number of considerations. SSRIs have a broad spectrum of antidepressant activity, being effective in different types of major depressive episodes (e.g., melancholic, atypical), have a wide therapeutic index, and are free of many potentially serious adverse effects associated with other antidepressants, such as central nervous system and cardiovascular toxicity (TCAs, bupropion), orthostatic hypotension (TCAs, MAOIs, and trazodone), and sedation (TCAs, trazodone). While SSRIs as a group share a common presumed mechanism of action, there are clinically important differences among the members of this class. First, the pharmacokinetics of sertraline are the same in both elderly and younger patients, whereas elderly, in comparison with younger, patients develop higher plasma levels of fluoxetine (and its active metabolite, norfluoxetine) or paroxetine, when given the same dose. Second, the SSRIs differ in their potential for pharmacokinetic interactions with other psychotropic and nonpsychotropic drugs. Fluoxetine, norfluoxetine (the major metabolite of fluoxetine), and paroxetine are potent inhibitors of the hepatic isoenzyme P450 IID6, whereas sertraline has much weaker inhibitory effects on its activity. Inhibition of P450 isoenzymes can cause potentially dangerous increases in the plasma levels of a large number of drugs, including TCAs, neuroleptics, and mood stabilizers, such as carbamazepine. Thus, sertraline has several characteristics that offer advantages over other members of this class of antidepressants for the treatment of the elderly patient with major depression. PMID- 8503478 TI - Differential diagnosis between depression and dementia. AB - The proportion of U.S. citizens > 65 years of age is growing steadily. This aging of the population is expected to bring an increase in the incidence of depression and dementia, two clinical entities common in elderly populations. Although depression and dementia have many similarities, they also have important clinical distinctions. It is important for primary-care physicians to understand these distinctions, since only approximately 20% of patients with depressive symptoms are treated by mental health practitioners. PMID- 8503479 TI - Intraoperative facial nerve monitoring: what is its appropriate role? PMID- 8503480 TI - Inner ear inflammation and round window otosclerosis. AB - Recently, it has been suggested that otosclerosis represents the host's ongoing immunologic response to measles or other viral antigens. Documentation of past inflammation within the inner ear would serve as further evidence that this mechanism may be at play in the pathogenesis of the disease. Among the characteristic signs of prior inflammation in the inner ear is the presence of lamellar bone at the site of inflammation. This has been described in the temporal bone of a patient with immune-mediated deafness and with the temporal bones of experimental models of immune-mediated inner ear disease. Review of temporal bones with round window otosclerosis from the Eastern Temporal Bone Bank at the Massachusetts Eye and Ear Infirmary show that in four of ten cases there are characteristic signs of a prior severe inflammatory event centered in the scala tympani adjacent to the otosclerotic lesion. Otosclerosis, therefore, may have an inflammatory stage that is the consequence of a host response to an inciting event. PMID- 8503481 TI - Stapedectomy surgery in residency: KTP-532 laser versus argon laser. AB - Stapedectomy for otosclerosis is one of the most demanding otologic procedures, especially for residents in training. The reported series in the literature, as well as our own experience with the traditional resident-performed complete stapedectomy, have been disappointing. The number of patients available to train residents in stapedectomy techniques has steadily declined. The challenge to the otologist involved in teaching residents and fellows is to find a method that will be safe and effective. Over the past 5 years, we have had an opportunity at the University of Texas Medical Branch at Galveston to compare two methods of performing a laser stapedotomy. The two methods involve using the KTP-532 laser with a micromanipulator and using the hand-held argon laser. Although the wavelengths of these two lasers are similar, the methods used in applying them are very different. Twenty-five consecutive cases in each group were reviewed with regards to technical difficulty, complication rate, operative time, and air borne gap closure. The hand-held argon laser emerged as the preferred technique for teaching a routine stapedotomy to residents. PMID- 8503482 TI - Reducing footplate complications in small fenestra microdrill stapedotomy. AB - Some surgeons have altered their technique for small fenestra stapedotomy in order to avoid footplate complications. This study aimed to determine what surgical step changes reduced footplate complications and improved hearing results. Operative reports provided data on surgical technique and complications in 151 consecutive primary stapes surgery patients. Comparisons of preoperative and postoperative audiograms provided hearing results of surgery. Fenestrating the footplate after, rather than before, stapes arch removal and fracturing the stapes arch after dividing one crus with a nipper were two surgical steps that reduced fractures. Hearing results were better after fenestration of the footplate with a microdrill compared to results with a hand drill. PMID- 8503483 TI - Endoscopic anatomy of the cerebellopontine angle. AB - This study describes the endoscopic anatomy of the cerebellopontine angle (CPA). Endoscopes were introduced into the basal cisterns and it was found that the neurovascular structures of this angle could be seen in detail. Endoscopy is likely to complement contemporary microsurgical procedures. The need for minimally invasive surgery may mandate further study of the application of this type of endoscopy in surgical practice. It is stressed that considerable cadaver experience should be obtained with this technique prior to any application in the operating room. PMID- 8503484 TI - Alteration in cholesteatoma fibroblasts: induction of neoplastic-like phenotype. AB - Cholesteatomas are invasive, locally destructive skin-like lesions that, after operative removal, have a significant recidivistic rate. These aggressive characteristics suggest a fundamental alteration in the biology of one or more of its constituents (i.e., keratinocytes, fibroblasts, and inflammatory cells). The cholesteatoma matrix was studied by subculturing it into its main cellular components. Short-term cell cultures of fibroblasts from cholesteatoma matrix and controls from ear canal and postauricular skin were established. These cultured fibroblasts were tested for invasiveness using the Boyden Chamber Assay of Albini. The cells were evaluated for their ability to migrate, attach to, and invade a basement membrane. Results of the motility and attachment of fibroblasts cultured from cholesteatoma, canal wall, and postauricular skin did not differ. However, fibroblasts from 12 of 12 cholesteatoma specimens were highly invasive, while those from postauricular and ear canal skin were either weakly invasive or not invasive. This represents the first report of an intrinsic defect in the biology of cholesteatoma. Invasive fibroblasts that demonstrate a loss of growth control, may provide a contact guidance mechanism that aggressively mobilizes the squamous keratinizing epithelium contributing to the invasive, aggressive behavior of cholesteatoma. PMID- 8503485 TI - Does the distribution of Schwann cells correlate with the observed occurrence of acoustic neuromas? . AB - Acoustic neuromas account for 75 to 80 percent of cerebellopontine angle tumors and 8 to 10 percent of all intracranial neoplasms. These tumors arise from the Schwann cell sheath that surrounds the peripheral portion of the facial, cochlear, superior, and inferior vestibular nerves. Theoretically, a schwannoma may arise from Schwann cells anywhere along these nerves from the glial-Schwann cell junction to the end organ. Clinically, however, they most frequently originate from the vestibular nerves, occasionally from the facial, and only rarely from the cochlear nerve. This investigation utilized light microscopy, immunochemistry, and digital optical morphologic analysis to determine the distribution of Schwann cells along the facial and vestibulocochlear nerves in an attempt to explain the observed distribution of tumors, and to evaluate currently accepted theories. No direct correlation between the distribution of Schwann cells and the observed distribution of schwannomas was found. Thus, this study did not confirm the currently held theories regarding schwannoma distribution in these nerves. PMID- 8503486 TI - Reporting the benefits from middle ear surgery using the Glasgow Benefit Plot. AB - In the past, otologists have reported the results of middle ear surgery to improve hearing, either by tympanoplasty or by stapes surgery, mainly in terms of closure of the air-bone gap. This is valid as a measure of the technical success of the operation provided any change in the bone conduction thresholds, particularly at the higher frequencies, is also reported. Unfortunately, technical success in surgery does not always equate with patient benefit, primarily because, in most conditions, listening is a binaural condition. Disability in such circumstances is dictated by the hearing in the better hearing ear, which, quite correctly, is usually the nonoperated ear. Hence, it is important to define the relationship, before and after surgery, between the hearing in the operated and that in the nonoperated ear. This is the basis of the Glasgow Benefit Plot, which is drawn up from pure-tone audiometric data before and after surgery. PMID- 8503487 TI - Ototoxicity and ototopical medications: a survey of otolaryngologists. AB - In an attempt to define the clinical parameters and relevance of ototopical medications, including their usefulness in permanent inner ear damage, a questionnaire survey was sent to 7463 otolaryngologists within the United States, of which 2235 responded. The four main categories were demographic data, patterns of practice, factors influencing use of ototopicals, and opinions/impressions of ototopicals under various circumstances. The vast majority of respondents use ototopical preparations in the presence of a draining perforation (84.1%), in the presence of drainage through a ventilation tube (93.7%), and in the presence of an open, draining tympanomastoid cavity (92.8%). A significant number of clinicians use ototopicals with intraoperative packing (75.3%) and postoperative prophylaxis against infection (57.9%). Eighty percent of respondents indicate that the risks for ototoxicity of otitis media is as great as, or greater than, the risks for ototoxicity of an ototopical preparation. Seventy-five percent of respondents stated that ototopicals are safe in a fresh postoperative ear. Some respondents (3.4%) reported that they had witnessed irreversible inner ear damage unquestionably related to ototopicals. PMID- 8503488 TI - Fibrin glue in otology and neurotology. AB - The recent development of simple, low-cost methods for producing autologous fibrin glue have given rise to a variety of uses in routine otologic and neurotologic procedures. Some of the current applications used by the authors are discussed, and a brief review of the literature is presented. Included are methods of positioning and securing implants, closure of wound edges, and application as an adjunct to achieving watertight dural closures with intracranial procedures. Representative cases are presented. No adverse reactions or specific problems related to the glue have been noted. A simple production method is included, as well as comparison with other commonly available tissue glue products. PMID- 8503489 TI - Evaluation of expandable leadwires for pediatric cochlear implants. AB - The development of cochlear implants for use in very young children (1-2 years old) will require techniques designed to accommodate temporal bone growth. Previous anatomic studies have shown that the leadwire of a cochlear implant must be capable of expanding up to 20 mm between the round window and the implanted receiver-stimulator in response to skull growth. In the present study morphologic and biomechanical evaluation of five expandable leadwire designs was conducted following their implantation in young cats. Two helical shaped leadwire designs frequently exhibited extensive fibrous tissue adhesions and broke during long term implantation. In contrast, thin, flexible Silastic envelopes were effective in minimizing tissue adhesions. Residual V- and Z-shaped leadwires, placed in these envelopes, showed little evidence of fibrous tissue adhesions following implantation periods of up to 2 years. Moreover, these leadwires readily expanded both during the growth of the animal and when biomechanical expansion studies performed at the completion of the implant period. These expandable leadwire designs appear to be appropriate candidates for use in pediatric cochlear implants. PMID- 8503490 TI - Diagnosis of vestibular Meniere's disease with electrocochleography. AB - The existence of vestibular Meniere's disease, once considered a variant of classic Meniere's disease, but without hearing loss, has been questioned because of lack of objective evidence that endolymphatic hydrops is involved with the disease process. Transtympanic electrocochleography (TT ECoG) has emerged as a useful tool for electrophysiologic monitoring of the inner ear, and is especially valuable in assessing endolymphatic hydrops. A retrospective chart review was performed to identify those patients with a diagnosis consistent with vestibular Meniere's disease in order to determine the presence or absence of endolymphatic hydrops using TT ECoG. A total of 15 patients were identified. Using established norms for the summating to action potential ratio (SP:AP) with click stimulus, 73 percent demonstrated values consistent with endolymphatic hydrops. The most commonly associated symptom was aural fullness (60%), followed by tinnitus (33%), and the disease was bilateral 53 percent of the time. The similarities between this clinical entity and classic Meniere's disease are noted, and theoretic considerations are made. PMID- 8503491 TI - Modified occipital approach to the endolymphatic sac and cochlear aqueduct of the guinea pig. AB - Obliteration of the endolymphatic sac reliably results in endolymphatic hydrops in some animal species. While this procedure is frequently utilized in the study of experimental Meniere's disease, additional information regarding inner ear fluid hydrodynamics can be obtained by obstructing the cochlear aqueduct to eliminate the influence of the cerebrospinal fluid on the perilymphatic compartment of the inner ear. This report describes a modified extradural occipital approach for surgical obliteration of the endolymphatic sac and obstruction of the cochlear aqueduct in the guinea pig. The extradural approach allows direct visualization of the cochlear aqueduct without manipulation or retraction of the dura, sigmoid sinus, or cerebellum. For experimental studies, which require obliteration of both the endolymphatic sac and cochlear aqueduct, this approach provides improved reliability with reduced morbidity and mortality. PMID- 8503492 TI - Medial meatal fibrosis: the University of Western Ontario experience. AB - Medial meatal fibrosis is an uncommon but surgically treatable cause of conductive hearing loss. A review of 10 years experience with this entity at The University of Western Ontario revealed a total of 15 cases involving nine patients. Each of them was treated by one of four otologists. This disease may arise from either recurring or chronic infection or from chronic dermatitis, and it frequently presents with bilateral involvement. It may occur at virtually any age, and to our knowledge, this series includes the first cases of this disease to be described in children. The medical and surgical management of this condition is described in detail and the results are summarized. PMID- 8503493 TI - Auditory brainstem response thresholds to air and bone conducted clicks in neonates and adults. AB - Auditory brainstem response (ABR) thresholds to air and bone conducted clicks were investigated in 20 full-term neonates and 20 normal-hearing young adults. Results showed mean ABR thresholds to air and bone conducted clicks for neonates to be 3.75 dB nHL (40.75 peak SPL) and 1.25 dB nHL (36.25 dB peak re: 1 microN), respectively, and for adults 3.75 dB nHL (40.75 peak SPL) and 18.75 dB nHL (53.75 peak re: 1 microN), respectively. A significant difference was observed in mean ABR thresholds to bone conducted stimuli between neonates and adults (p < 0.0001) and among mean adult ABR thresholds to air and bone conducted stimuli (p < 0.0001). Nonsignificant differences were observed in mean ABR thresholds to air and bone conducted stimuli among neonates (p > 0.05) and in mean ABR thresholds to air conducted stimuli between neonates and adults (p = 1.00). It is speculated that the dissimilarity in the relationship of thresholds to air and bone conducted stimuli between neonates and adults reflects, in part, a difference in efficiency of signal delivery to the cochlea. PMID- 8503494 TI - Treatment of idiopathic sudden sensorineural hearing loss. AB - A retrospective review was done, examining the charts of 41 patients admitted to The Eye and Ear Hospital of Pittsburgh with a diagnosis of sudden hearing loss (SHL). Treatment consisted of (1) systemic steroids; (2) daily intravenous histamine infusion; and (3) carbogen (95% oxygen and 5% CO2) inhalation. Parameters examined included age, sex, duration of symptoms prior to admission, days hospitalized, side of lesion, vestibular symptoms, tinnitus, blood work, radiography, vestibular function (ENG), and serial audiograms. Fifty-four percent showed improvement in hearing, defined as at least a 10-dB increase at any frequency following therapy. There was no correlation of preexisting signs, symptoms, or findings with hearing recovery. Since the natural history of this process demonstrates spontaneous improvement in approximately two thirds of patients without treatment, we conclude that for the group of patients that we treated, our therapeutic regimen was ineffectual. PMID- 8503495 TI - Ototoxicity of erythromycin in man: electrophysiologic approach. AB - Ototoxicity is probably the least acknowledged adverse reaction of erythromycin. The mechanism of erythromycin ototoxicity is still unknown. Here we report on two new cases of erythromycin-induced hearing loss. In both of them, serial evoked auditory brainstem potentials (EABPs) were obtained. The recorded EABPs showed absence of waves I to III during treatment with erythromycin, and normalization of all EABP waves after the administration of erythromycin had been stopped. Our findings support the hypothesis that erythromycin-induced hearing loss is attributable to a functional disorder in the peripheral parts of the auditory system. PMID- 8503496 TI - Asymptomatic osteomas of the middle ear. AB - Osteomas of the middle ear are extremely rare lesions. Of the nine cases reported, eight presented with conductive hearing loss. We recently treated two patients whose osteomas, of the promontory and of the posteroinferior tympanic wall, were asymptomatic. We suggest that middle ear osteomas need not be removed when they do not impinge on the sound conduction system. PMID- 8503497 TI - Bilateral congenital cholesteatomas. AB - Congenital cholesteatoma is a rare entity. Bilateral involvement is rarer still. We present the sixth case of bilateral congenital cholesteatoma and briefly review the theories regarding the origin of congenital cholesteatoma. The lesion in the left ear was seen on physical examination, however the lesion in the right ear was detected only on a computed tomography (CT) scan, which was obtained to assess the extent of the disease on the left side. Although usually asymptomatic, these cholesteatomas can enlarge and lead to complications. Management of congenital cholesteatoma by various surgical approaches is discussed. PMID- 8503498 TI - Effect on endocochlear potential of streptomycin perfusion of the cochlea in guinea pigs. AB - Perilymphatic perfusion of the cochlea with streptomycin was performed on 17 guinea pigs. The first and second group, consisting of five animals each, received streptomycin 150 micrograms and 1500 micrograms respectively. In a control group, consisting of seven animals, the perilymph was perfused with artificial perilymph only. The endocochlear potential (EP) was recorded from the second turn of the cochlea in each animal. The results indicate that streptomycin in a low dosage that will destroy the vestibular receptors was not harmful to the function of either the stria vascularis or the hair cells in the cochlea, as measured by changes in the EP after streptomycin perfusion of the cochlea. PMID- 8503499 TI - Recurrent rates of acoustic neuroma in hearing preservation surgery. PMID- 8503500 TI - Cerumen management. PMID- 8503501 TI - Innovation at the work site: delivery of nurse-managed primary health care services. PMID- 8503502 TI - Qualitative analysis of mycotoxins using micellar electrokinetic capillary chromatography. AB - Naturally occurring mycotoxins are separated using micellar electrokinetic capillary chromatography. Trends in the retention of these toxins, resulting from changes in mobile-phase composition and pH, are reported and presented as a means of alleviating coelution problems. Two sets of mobile-phase conditions are determined that provide unique separation selectivity. The facile manner by which mobile-phase conditions can be altered, without changes in instrumental configuration, allowed the acquisition of two distinctive, fully resolved chromatograms of 10 mycotoxins in a period of approximately 45 min. By adjusting retention times, using indigenous or added components in mycotoxin samples as normalization standards, it is possible to obtain coefficients of variation in retention time that average less than 1%. The qualitative capabilities of this methodology are evaluated by separating randomly generated mycotoxin-interferent mixtures. In this study, the utilization of normalized retention times applied to separations obtained with two sets of mobile-phase conditions permitted the identification of all the mycotoxins in five unknown samples without any misidentifications. PMID- 8503503 TI - Enzyme-linked immunosorbent assay for an octapeptide based on a genetically engineered fusion protein. AB - Traditional chemical means of preparing enzyme-ligand conjugates for use in enzyme-linked immunosorbent assays (ELISAs) lead to the production of multisubstituted enzyme-ligand conjugates with a high degree of variability in the site of ligand attachment. A genetically engineered fusion protein was prepared in order to investigate the feasibility of controlled production of conjugates for use in ELISAs. Specifically, a synthetic octapeptide was fused with bacterial alkaline phosphatase. The resulting enzyme-peptide conjugate is monosubstituted (one peptide per subunit), has a single site of attachment, and results in assays with good response characteristics. The use of such fusion proteins, which combine small analyte peptides with enzyme labels, can lead to a new approach to improved assays for numerous biomolecules, including peptide pharmaceuticals, neurotransmitters, hormones, cell surface antigens, etc. PMID- 8503504 TI - Noncompetitive flow injection immunoassay for a hapten, alpha (difluoromethyl)ornithine. AB - A noncompetitive flow injection immunoassay method has been developed to assay small haptens. In this assay the sample containing the hapten is incubated with excess enzyme-labeled monovalent antibody for a brief period. The excess antibody is then separated from the bound antibody by eluting through an antigen immobilized immunoaffinity column. The enzyme label of the eluting antibody hapten complex is fluorometrically detected. The applicability of the method is demonstrated by assaying alpha-(difluoromethyl)ornithine (DFMO), an anticancer drug in human plasma samples. The assay is sensitive enough to detect 200 amol of DFMO. Interferences from other similar endogenous amines have been eliminated by selective immunoaffinity purification of the antibodies. PMID- 8503505 TI - Near-IR imaging of atheromas in living arterial tissue. AB - A near-IR imaging system and parallel vector supercomputer are used with a fiber optic probe to produce chemical maps of the intimal surface of living arteries. Spectrometric information collected at hundreds of near-IR wavelengths is assembled into color pictures of the lipoprotein and apolipoprotein composition of atheromas using a vectorized 3-D cellular automaton-based algorithm that operates in parallel. The nonparametric mathematics developed to identify and quantify the constituents of each voxel in the artery wall avoid the matrix factorizations that generate excess error in other pattern recognition methods and permit analysis in a wavelength space of over 1000 dimensions using fewer than 100 calibration samples. A surface feature resolution of 5.5 microns and depth resolution of 6.5 microns are achieved with the system. Data from the fiber optics confirm the injury hypothesis of lesion formation and the differing roles of HDL and LDL in cholesterol transport. In clinical studies, approximately 1/2 of human arterial lesions appear fibrous and contain little or no lipid. As such, these lesions would not be expected to regress in response to cholesterol lowering agents such as lovastatin. Identification of lesion types in vivo will enhance the efficacy of treatment programs. PMID- 8503506 TI - Stored waveform inverse Fourier transform axial excitation/ejection for quadrupole ion trap mass spectrometry. AB - A general method for high-resolution ion excitation, ejection, and isolation is developed from linear response theory for resonant dipolar excitation of the axial z-oscillatory motion of ions in a quadrupole (Paul) ion trap operated in rf only mode. For a spatially uniform dipolar excitation field, the ion z oscillation amplitude is directly proportional to the amplitude of the Fourier component of the excitation at the axial oscillation frequency of that ion. Thus, one may specify an arbitrary z-motion frequency-domain spectrum by applying a time-domain stored waveform obtained from the inverse Fourier transform of the corresponding frequency-domain excitation spectrum. The stored waveform inverse Fourier transform (SWIFT) waveform may be tailored for selective ejection or excitation of ions of arbitrary mass-to-charge ratio ranges. The method includes all other possible excitation/ejection waveforms (e.g., single frequency, frequency sweep) as special cases. The effect of collisional damping during excitation is included in the analytical solution of the ion response. PMID- 8503507 TI - Clinical and angiographic features of patients with an occluded versus a patent infarct vessel after intravenous streptokinase for acute myocardial infarction. AB - Despite early treatment with thrombolytic agents for acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. To study the various factors related to achieving patency in the infarct vessel, 201 patients who received streptokinase within six hours of symptoms were studied. All patients underwent cardiac catheterization during the same hospitalization at 5.40 +/- 3.26 days after admission. Forty-five (22.4%) patients were found to have an occluded infarct artery (group 1) and 156 (77.6%) had a patent infarct vessel (group 2). There was no difference in the time from onset of symptoms to receiving streptokinase between the two groups. The two groups were similar to each other with regard to age, gender, history of myocardial infarction or angina, and major risk factors for coronary disease. Coagulation parameters before and after streptokinase therapy, reflecting the lytic state, were similar in both groups. The left ventricular end diastolic pressure was significantly higher and the left ventricular ejection fraction was significantly lower in group 1 than in group 2. These observations suggest that despite early initiation of thrombolytic therapy in patients with acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. This failure cannot be explained by the observed clinical parameters or the lytic state after streptokinase. PMID- 8503508 TI - Risk factors for carotid atherosclerosis and silent cerebral infarction in patients with coronary heart disease. AB - In this study, the authors examined relations between coronary and carotid atherosclerosis and between coronary atherosclerosis and silent cerebral infarction. They ascertained the risk factors for carotid atherosclerosis and silent cerebral infarction complicating coronary heart disease (CHD) in 77 Japanese subjects. As coronary atherosclerosis progressed, the carotid ultrasonographic score and the brain computed tomographic score increased. Multivariate analyses showed that the significant and independent risk factors for carotid atherosclerosis in patients with CHD were age (p < 0.01) and apolipoprotein (apo) B (p < 0.05) and the factors for silent cerebral infarction were age (p < 0.05) and hypertension (p < 0.05). Their study confirms a positive relation between coronary atherosclerosis and carotid atherosclerosis and between coronary atherosclerosis and silent cerebral infarction in patients with CHD. Their data suggest that carotid atherosclerosis should be looked for in patients with CHD who are old and have a high value of apo B, and silent cerebral infarction should be looked for in those who are old and have hypertension, to prevent complicating symptomatic cerebral vascular disease (CVD). If severe carotid atherosclerosis or silent cerebral infarction are detected, antithrombotic medication should be given. PMID- 8503509 TI - Coronary thrombolysis and endothelin-1 release. AB - The relation between intracoronary thrombus and endothelin-1 (ET-1) was studied. In a canine model, acute myocardial infarction (MI) was induced by coronary occlusive thrombus produced at a mock atheromatous plaque. Blood samples were collected from the aorta (A) and coronary vein (V). Twenty-eight open-chest dogs divided into three groups were studied. Group I (n = 15): acute MI was induced by coronary occlusive thrombus, and thrombolysis was obtained by urokinase two hours after MI. Group II (n = 8): nonocclusive thrombus was produced without inducing MI. Group III (n = 5): coronary artery was ligated for two hours and reperfused by release of ligation. In Group I, ET-1 was significantly increased after MI in A and V, and ET-1 in V was significantly more elevated than in A during thrombolysis, suggesting ET-1 production in the coronary vessels by thrombolysis. In Group II, ET-1 increased slightly during thrombus formation, but there was no difference in A and V. In Group III, ET-1 was elevated significantly after MI without A and V difference. These results indicate that there is no detectable ET 1 production with coronary thrombus formation, whereas coronary ET-1 production is detected during thrombolysis, most probably because resolved thrombus releases a more potent stimulus to ET-1 production. PMID- 8503510 TI - Prevalence of ventricular premature complexes in healthy and untreated hypertensive elderly people. AB - Twenty-four-hour ambulatory electrocardiographic examination was performed in 130 elderly patients (49 healthy, active subjects; 40 hypertensive without left ventricular hypertrophy; and 41 hypertensive with left ventricular hypertrophy). In the study group, mean age was 72.4 +/- 7.1 (sixty-five to eighty-eight) years. A significantly high prevalence of ventricular ectopic complexes was found both in hypertensive and in normotensive groups. According to the Lown grades, in grade 1, VPCs had very high prevalence in healthy subjects, in grade 2, VPCs had a high prevalence in hypertensives with left ventricular hypertrophy (73.5% and 48.8%, respectively). The results of this study demonstrate that ventricular premature complexes were common in hypertensive patients and healthy elderly but did not cause high complexity in either group. Ventricular premature complexes detected by ambulatory ECG monitoring in healthy, active subjects and in untreated hypertensive patients are not an independent risk factor in elderly patients. PMID- 8503512 TI - The importance of the subfascial lymphatics in the diagnosis of lower limb edema: investigations with semiquantitative lymphoscintigraphy. AB - A new method of semiquantitative lymphoscintigraphy for the evaluation of lower limb edema is characterized by (1) the evaluation of both the epifascial and subfascial system in order to assess type and stage of the edema, (2) the use of high-resolution digital whole-body imaging to facilitate the calculation of functional parameters, and (3) the use of active, standardized ergometry for reproducibility. The appearance time of 99mTc-labeled human albumin nanocolloid in inguinal lymph nodes after injection and the percent uptake of colloid into lymph nodes at 40 and 120 min after injection served as functional parameters. Patients with edema of the lower limb were compared with normal subjects. In patients with primary lymphedema the two lymphatic compartments are functionally compromised. Early and advanced stages of postthrombotic syndromes can be distinguished by characteristic lymphoscintigraphic patterns in epifascial and subfascial lymphatic compartments. These results indicate that only the separate evaluation of both the epifascial and subfascial compartments allows an accurate functional assessment of the lymphatics in lower limb edema. PMID- 8503511 TI - Results of directional peripheral atherectomy with reference to histology, histochemistry, and ultrastructure. AB - One hundred patients with symptomatic peripheral vascular disease were treated with a directional atherectomy catheter; 153 lesions comprising 98 stenoses and 55 occlusions were located in the iliac (n = 22), superficial femoral (n = 114), popliteal (n = 16), and anterior tibial (n = 1) arteries. The majority of these patients were poor candidates for balloon angioplasty because of the complexity of lesions. There were 70 eccentric and 28 concentric lesions and 55 occlusions (mean length 4.2 +/- 2.9 cm). Acute success rate was 94% for both stenoses and occlusions. Four patients were treated in both lower extremities. The stenoses were reduced from 85 +/- 12% to 12 +/- 10% acutely (occlusions 100% to 9 +/- 9%). Six-month angiographic follow-ups were performed in 81% of treated patients, the others refusing angiography. Mean stenosis after six months was 33 +/- 25% (occlusions 44 +/- 28%). Restenosis (> 50%) was found in 20% of treated lesions: 26% in concentric lesions, 8% in eccentric lesions, and 32% in occluded vessels. Treatment of peripheral vascular disease with the atherectomy device is safe and effective therapy with good long-term results. These results were obtained in complex lesions with 55 occlusions. Atherectomy seems to be particularly beneficial in the treatment of eccentric and complex stenoses and is not limited by occlusion or calcification. Furthermore, insight into the pathogenesis of arteriosclerosis and the development of restenosis is enabled by analysis of removed plaque material. PMID- 8503513 TI - Oxygen transport in peripheral arterial occlusive disease: effects of calf blood dialysate. AB - The obvious relationship of arterial blood flow to tissue hypoxia has led to the relative neglect of secondary mechanisms that might influence the functional and morphologic consequences of major vessel obstruction. Oxygen diffusion through capillaries, both locally and systemically, may be disturbed in subjects with chronic local ischemia. Follow-up data after a double-blind, placebo-controlled evaluation of the effect of treatment with a calf blood dialysate confirm that such treatment may alleviate the consequences of peripheral arterial obstructive disease even though there is no improvement in blood flow through the arterial system involved. PMID- 8503514 TI - Extraaortic intimomedial mucoid degeneration: a clinicopathological study. AB - Six black patients with extraaortic intimomedial mucoid degeneration of the major arterial branches of the aorta are reported. Five patients presented with aneurysmal dilatation of the arterial wall as a result of the intimomedial mucoid degeneration, and the sixth patient had superimposed occlusive thrombosis. The ages ranged from twenty to fifty years. Five patients were female. Two were hypertensive. All patients in this study underwent reconstructive vascular surgery. The clinical and histopathologic findings are discussed. PMID- 8503515 TI - Nitric oxide mediates vasoactive effects of endothelin-3 on rat mesenteric microvascular beds in vivo. AB - In order to clarify whether the vasoactive effects of endothelin-3 (ET-3) on microvessels are associated with the endothelium-derived relaxing factor (EDRF) in vivo, the authors examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced hemodynamic changes in the mesenteric microcirculation of male Wistar rats. The intravital observation revealed that ET-3 100 pM induced a remarkable and periodic vasoconstriction in arterioles, and the constriction was sustained for approximately fifteen minutes. No remarkable change was observed in the microvessels after the superfusion of 1 pM ET-3. Superfusion of 1 pM ET-3 with 100 microM L-NMMA elicited the vasoconstriction in arterioles, and the arteriolar diameter recovered to the control level within ten minutes in spite of continuing the superfusion. The vasoconstriction induced by low-dose ET-3 with L-NMMA was suppressed by the additional superfusion of 200 microM L-arginine. The present study suggests that the recovery of arteriolar diameter after the ET-3-induced constriction may be mediated by nitric oxide at least in the early phase. PMID- 8503516 TI - Abdominal aortic aneurysms in familial hypercholesterolemia--case reports. AB - Familial hypercholesterolemia (FH) is a genetic disease characterized by high serum cholesterol levels and premature coronary atherosclerosis. Hypercholesterolemia is one of the factors promoting the arteriosclerotic process and is a major cause of aortic aneurysm. Few data are available, however, about abdominal aortic aneurysms (AAAs) in patients with FH. In this study, the clinical and angiographic characteristics of AAAs found in patients with FH were investigated. Thirty-one cases (23 men, 8 women, aged fifty +/- fourteen years) were examined by coronary angiography, thoracic and abdominal aortography, and clinical data. Abdominal aortography detected abdominal aneurysms in 8 cases (26%), all of whom were men, including 4 cases (50%) that were complicated by diabetes mellitus. The abdominal aneurysm patients manifested severe coronary atherosclerosis, severe abdominal aortic irregularity, and higher blood pressure than the nonaneurysm FH patients. These findings suggest that AAAs are an important and prevalent feature in FH, especially in men with diabetes mellitus and high blood pressure. PMID- 8503517 TI - Bilateral perinephric fluid accumulation: an unusual manifestation of pulmonary hypertension--a case report. AB - This is the case report of a forty-seven-year-old man with an ostium secundum atrial septal defect and a very high grade of pulmonary hypertension, associated with a large bilateral perinephric fluid accumulation. The fluid accumulation was remarkably reduced after eleven phlebotomies over a twelve-month period. A pathogenetic relation with the Eisenmenger's syndrome is discussed. No previous report of this association has been found in a survey of the literature. PMID- 8503518 TI - Accelerated idioventricular rhythm in pregnancy: a case report. AB - A seventeen-year-old primigravida, without structural heart disease or abnormalities of serum chemistry, presented with complaints of palpitations during the twenty-fourth week of gestation. Holter monitoring revealed long episodes of accelerated idioventricular rhythm. The authors are not aware of similar reports, but this entity may be more common than realized because of the relative infrequency of rhythm monitoring in this particular group. PMID- 8503519 TI - Patients who talk and deteriorate. AB - Patients who "talk and deteriorate" are defined as those who utter recognizable words at some time after head injury and then deteriorate to a severe head injured condition (Glasgow Coma Scale score of 8 or less) within 48 hours of injury. They represent a very small but important subgroup of patients with brain injury. In approximately 75% of these patients, the cause of this deterioration is intracranial hematoma. Despite the fact that talking indicates nonlethal impact brain injury, deterioration is a marker of poor prognosis. Outcome depends on early recognition of deterioration and rapid removal of mass lesions. The challenge for emergency physicians is to distinguish patients at risk for deterioration from the many patients evaluated after head injury. PMID- 8503520 TI - Rapid-sequence intubation in head trauma. AB - Elevated intracranial pressure commonly is associated with severe head injury. Emergency airway management technique in the patient who has sustained severe head injury must optimize conditions for intubation, minimize the adverse effects of intubation, and permit rapid and effective management of the elevated intracranial pressure. Disturbances in autoregulation make the injured brain particularly susceptible to the adverse effects of alterations of systemic blood pressure. Airway manipulation without adequate pharmacologic support can cause precipitous changes in systemic hemodynamic parameters. This article reviews the physiologic and pathologic relationship among airway management, systemic hemodynamic parameters, and intracranial pressure. Specific recommendations for the use of neuromuscular blocking agents, anesthetic induction agents, and adjunctive medications are provided. PMID- 8503521 TI - Cerebral ischemia-reperfusion injury after severe head injury and its possible treatment with polyethyleneglycol-superoxide dismutase. AB - Oxygen radical-mediated mechanisms play a role both in cerebral ischemia reperfusion injury and in traumatic brain injury. Moreover, my work with measurements of cerebral blood flow with the 133Xe method and the stable xenon computed tomography method and through measurements of arteriovenous difference of oxygen indicates that ischemia and ischemia-reperfusion are also part of traumatic brain injury but only in the first few hours after injury. The contributions of the research laboratories at the Medical College of Virginia, Richmond, to the understanding of the role of oxygen free radicals in traumatic brain injury are discussed. Finally, a trial of the oxygen radical scavenger polyethyleneglycol-superoxide dismutase in human beings with severe head injuries show that death and vegetative state occurred twice as often in the 26 patients receiving placebo compared with the group of 26 patients receiving a 10,000 U/kg bolus of polyethyleneglycol-superoxide dismutase (43%, respectively; 20% at three months; P < .03). PMID- 8503522 TI - Lipid antioxidants in acute central nervous system injury. AB - Oxygen radical-mediated lipid peroxidation increasingly has been suggested to be an important factor in post-traumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacologic agents with lipid antioxidant activity in models of spinal cord and brain injury. The glucocorticoid steroid methylprednisolone has been shown to possess significant antioxidant efficacy, and when administered to animals or human beings in antioxidant doses, it improves chronic neurologic recovery after spinal cord injury. This activity of methylprednisolone is independent of the steroid's glucocorticoid receptor-mediated actions and has been surpassed by the novel antioxidant 21-aminosteroids that have been developed that are devoid of glucocorticoid activity but have greater antioxidant efficacy than methylprednisolone. One of these, tirilazad mesylate (U-74006F), has been shown to be quite effective in animal models of brain and spinal cord injury and is the subject of phase III clinical trials. The consistent benefit afforded by antioxidant compounds further supports the concept that lipid peroxidation is an important therapeutic target for acute pharmacologic neuroprotection. PMID- 8503523 TI - Past and current clinical studies with GM-1 ganglioside in acute spinal cord injury. AB - Two recent prospective, randomized, placebo-controlled, double-blinded clinical drug studies in acute spinal cord injury have reported enhancement of neurologic recovery of motor function. The drugs investigated in these studies were methylprednisolone and GM-1 ganglioside. Before these studies, the treatment of patients with spinal cord injuries had been restricted to prevention of further injury to the spinal cord, limiting secondary damage following the initial injury, increasing the patient's ability to function through intensive rehabilitation, and facilitating any spontaneous recovery of neurologic function. Methylprednisolone is a steroid administered at very high levels, and GM-1 is a complex acidic glycolipid found at high levels in cell membranes in the mammalian central nervous system with known neuroprotective and neurofunctional restoration potential. This article summarizes the previously reported Maryland GM-1 clinical trial and presents the clinical and statistical design of a larger clinical trial being conducted with the purpose of verifying a beneficial GM-1 drug effect when administered with methylprednisolone in acute spinal cord injury. PMID- 8503524 TI - Mild traumatic brain injury syndrome. AB - The mild post-traumatic brain injury syndrome has continued to pose clinical management problems for medical specialists from the emergency physician to the family practitioner. The contribution of preinjury medical and psychosocial factors, along with the concomitant risk of litigation, complicates the diagnostic task. This review examines selected aspects of this problem, including definition and classification, pathophysiology, symptom constellation, medicolegal pitfalls, diagnostic procedures, and treatment recommendations. Practitioners need to be particularly alert to the optimal strategies for emergency department management to prevent "mild" injuries from becoming major disabilities. PMID- 8503525 TI - Evaluation and significance of the pupillary light reflex in trauma patients. AB - The pupillary light reflex is an important component of the neurologic examination of the trauma victim. Although the normal reflex can be predictably altered by specific head injuries, a variety of other factors common to trauma patients such as alcohol, illicit drugs, narcotics, paralyzing agents, hypothermia, and orbital or ophthalmic injury can confound the evaluation of the pupillary light reflex. This report reviews the anatomy and neurophysiology of the pupillary light reflex and discusses the impact these confounding variables may have on this key component of the initial trauma evaluation. PMID- 8503526 TI - The ACEP research forum: what's it all about? PMID- 8503528 TI - Vertebral artery thrombosis due to motor vehicle accident. AB - Vertebral artery injury is a relatively rare cause of neurologic deficits occurring after blunt trauma. We present the case of a man involved in a motor vehicle accident with resulting vertebral artery injury whose symptoms did not appear until several hours after his initial evaluation in the emergency department. The mechanisms, pathogenesis, presentation, and treatment of these injuries are discussed. PMID- 8503527 TI - Injuries resulting from bungee-cord jumping. AB - A 19-year-old woman sustained a nonfatal hanging injury and a 28-year-old man sustained a unilateral locked facet with resultant quadriplegia as a result of bungee jumping. Injuries due to this sport have not been reported previously. PMID- 8503529 TI - Complications following minor trauma in a patient with diffuse idiopathic skeletal hyperostosis. AB - Diffuse idiopathic skeletal hyperostosis is a little known but potentially devastating ankylosing disorder of the spine. It has been associated with fractures following minor trauma, which tend to be unrecognized, unstable, and associated with treatment delays and permanent neurologic deficits. We present a case of minor trauma to an elderly patient with diffuse idiopathic skeletal hyperostosis who subsequently developed severe neurologic deficits and later died of complications related to the disease. Diagnostic criteria, prevalence, and sequelae of diffuse idiopathic skeletal hyperostosis are discussed. PMID- 8503531 TI - Vulvovaginal water-skiing injury. PMID- 8503530 TI - Rapid-sequence intubation of head trauma patients. PMID- 8503532 TI - Guidelines for trauma care systems. American College of Emergency Physicians. PMID- 8503533 TI - Clinical policy for the initial approach to patients presenting with acute blunt trauma. American College of Emergency Physicians. PMID- 8503534 TI - Basic mechanisms of traumatic brain damage. AB - Brain damage induced by blunt head trauma is multifactorial in that the initial injury both induces extensive depolarization and damages tissue through transient sheer forces that mechanically deform tissue components, especially axons and microvessels. Furthermore, although there is little evidence for initial energy depletion, subsequent tissue edema and microvascular perfusion shunting may result in areas of focal ischemia. This review suggests that these events lead to a final common pathway of neuronal death that involves loss of cellular calcium homeostasis, production of injurious free radicals, and tissue acidosis. PMID- 8503535 TI - Brain injury and repair mechanisms: the potential for pharmacologic therapy in closed-head trauma. AB - Rotational acceleration from closed-head trauma produces shear-strain brain injury at the interface of gray and white matter. The initial injury is followed by progressive damage involving three key phenomena: progression of subtle focal axonal damage to axonal transection between six and 12 hours after injury, progressive development of tissue microhemorrhages between 12 and 96 hours after injury, and development of tissue and cerebral spinal fluid lactic acidosis that does not appear to be explained by trauma-induced tissue depolarization, activation of phospholipases and the release of free arachidonic acid, radical generation by metabolism of arachidonate, and lipid peroxidation with consequent membrane degradation and partial mitochondrial uncoupling. Because of terminal differentiation, neurons may have a limited membrane repair capability that might be stimulated by growth factors. Other potential therapeutic interventions include calmodulin inhibitors, iron chelators, and free radical scavengers. PMID- 8503536 TI - Pathobiology of traumatically induced axonal injury in animals and man. AB - STUDY OBJECTIVES: Although diffuse axonal injury is recognized as a consistent feature of traumatic brain injury, there is confusion regarding its pathogenesis. To provide insight into its pathogenesis, animal models of traumatic brain injury complemented by post mortem human analyses were used. DESIGN: In animals, anterograde tracers together with antibodies targeting the neurofilament subunits were used in light and electron microscopic analyses of axonal injury. In humans, antibodies to the neurofilament subunits also were used to follow diffuse axonal injury. Animals were followed from minutes to months after injury, whereas humans were studied from six hours to 59 days after injury. MEASUREMENTS AND MAIN RESULTS: In neither animals nor humans did traumatic brain injury cause direct axonal tearing. Instead, the traumatic brain injury triggered focal intra-axonal change in the 68-kd neurofilament subunit, which became disordered in its alignment and resulted in impaired axoplasmic transport. This caused axonal swelling and disconnection. The sequence of axonal change was similar in animals and man; however, its temporal progression was slower in humans. CONCLUSION: Traumatically induced axonal damage is triggered first by focal intra-axonal change involving the neurofilament subunits. This neurofilament change is due to either direct mechanical failure of the axonal cytoskeleton or the initiation of a biochemical event that causes neurofilament disassembly. In general, the temporal progression of the intra-axonal changes that lead to ultimate disconnection is influenced by the severity of the traumatic injury and the species evaluated. PMID- 8503537 TI - Pathophysiology of spinal cord trauma. AB - This article reviews the pathophysiology of spinal cord injury. The focus is on the role of post-traumatic membrane lipid changes, including lipid hydrolysis with enzymatic lipid peroxidation (ie, eicosanoid production) and nonenzymatic, free radical-induced lipid peroxidation in the secondary autodestruction of injured spinal cord tissue. A speculative etiopathogenesis of secondary injury is presented in an attempt to explain the importance and order of the pathophysiologic events that result in tissue death and the apparent effectiveness of diverse pharmacologic agents in the treatment of experimental spinal cord injury. PMID- 8503538 TI - Clinical considerations in the reduction of secondary brain injury. AB - Craniocerebral trauma renders the brain vulnerable to a variety of secondary insults that must be prevented or promptly corrected before irreversible neurologic damage occurs. These secondary insults can include hypoxia, ischemia, or both, which result in significant cell loss. The trauma-induced state of vulnerability appears to be due to cellular ionic and metabolic alterations that make up the basic physiologic sequelae after brain injury. We discuss clinical aspects regarding these potentially devastating injuries in an effort to enhance their recognition and aid in their management. PMID- 8503539 TI - The management of cerebral perfusion pressure and intracranial pressure after severe head injury. AB - Neurosurgical intervention attempts to minimize secondary central nervous system injury after severe head injury through the evacuation of mass lesions with subsequent manipulation of cerebral perfusion pressure and intracranial pressure. The normal brain couples blood flow to metabolic demand through autoregulation of the cerebral vasculature. After severe head trauma and its attendant increase in intracranial pressure, marked alterations in cerebral blood flow and perfusion may occur. Currently, intervention is based on maintenance of coronary perfusion pressure and aggressive management of intracranial pressure. Both may be impacted by manipulation of ventilation, systemic blood pressure and volume status, administration of osmotic diuretics, and head elevation. Such therapy in the patient with severe head injury attempts to maintain coronary perfusion pressure and adequate oxygen delivery in a damaged central nervous system with altered hemodynamics and raised intracranial pressure. PMID- 8503540 TI - Particulate air pollution and health. New evidence on an old problem. PMID- 8503541 TI - Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate chronic obstructive pulmonary disease. AB - This study assessed the association between respirable particulate air pollution (PM10) and changes in the pulmonary function (FEV1, FEV1/FVC, and FVC) of smokers with mild to moderate airflow limitation. Spirometric data of Salt Lake City participants in The Lung Health Study were used from two screening visits 10 to 90 days apart after an initial screening visit, which included spirometry. We analyzed differences in pulmonary function (delta FEV1, delta FEV1/FVC, and delta FVC) for participants between the two spirometry visits. Significant associations between changes in pulmonary function and PM10 were observed. delta FEV1 and delta FEV1/FVC were inversely associated with changes in PM10. Although these associations were small, explaining only about 2 to 3% of the variance in delta FEV1, they were consistently negative and statistically significant (p < or = 0.01). On average, an increase in PM10 equal to 100 micrograms/m3 was associated with a marginal decline in FEV1 equal to approximately 2%. Associations between delta FVC and PM10 were consistently negative, but they were not statistically significant. No consistent or statistically significant associations between delta FEV1, delta FEV1/FVC, or delta FVC with changes in daily temperatures were observed. The effect of PM10 was greater for men than for women. The effect was nearly the same for those with nonspecific airway hyperresponsiveness (AHR), based on methacholine inhalation challenge testing, versus those without AHR. We conclude that in current smokers PM10 possibly has a small transient negative effect on lung function that is not entirely obscured by their smoking habit. PMID- 8503542 TI - Asbestos-related radiographic abnormalities in elevator construction workers. AB - Elevator construction workers are exposed to asbestos dust during construction and refurbishment work on older buildings. We screened a cohort of workers, all with greater than 20 yr of employment in the industry, with clinical examinations, chest radiography ("B" reader interpretations), and routine spirometry. Twenty of the 91 workers (22%) had evidence of pleural disease, but none of them had an interstitial process consistent with asbestosis. Of those with pleural thickening, 15 had bilateral circumscribed plaques and five had unilateral plaque formation. There were no cases of diffuse pleural thickening, benign pleural effusions, or mesothelioma identified in our cohort. The difference in the mean body mass index of those with pleural abnormalities (29.18 +/- 3.95) and those without (27.7 +/- 3.86) was not statistically significant (p = 0.135). We conclude that elevator construction workers have an increased risk for the development of asbestos-related pleural disease. PMID- 8503544 TI - Prediction of lung function in Hispanics using local ethnic-specific and external non-ethnic-specific prediction equations. AB - We compared locally derived prediction equations for the FVC and FEV1 in Hispanics with external prediction equations derived from non-Hispanic whites. Algebraic subtraction of the external non-Hispanic equations from the New Mexico Hispanic equations showed that the differences would vary with age and height. The study population included 442 patients with Hispanic surnames between the ages of 25 and 80 yr evaluated at the University of New Mexico Hospital pulmonary function laboratory. We calculated percent predicted values for FVC and FEV1 using spirometric prediction equations from a New Mexico Hispanic population and from non-Hispanic white populations in Salt Lake City, Tucson, and six other U.S. cities. We employed either 80% of predicted or the lower fifth percentile as the criterion for separating normal from abnormal values. We found that the concordance of the classifications by the external and internal equations varied among the external equations and with the criterion used for abnormality. The classification of the FVC and FEV1 as normal or abnormal was influenced by the regression equation in about 5 to 10% of the subjects. Subjects with discordant classifications were not clearly predicted by age or height, although they tended to be at the extremes of the age and height distributions. This study shows that classification of lung function by locally derived ethnic-group-specific prediction equations may lead to a differing clinical categorization for some persons in comparison with external non-ethnic-group-specific equations. PMID- 8503543 TI - A longitudinal study of plasma cortisol concentration and pulmonary function decline in men. The Normative Aging Study. AB - Because of the important role of peripheral airways inflammation in the pathogenesis of asthma and COPD and because of the known anti-inflammatory actions of corticosteroids, we hypothesized that endogenous cortisol may influence the rate of decline of pulmonary function with aging. We examined the basal plasma cortisol concentration and serial spirometric measurements of 86 healthy men participating in the Normative Aging Study. Subjects selected for this study were free of any chronic illnesses and denied chronic use of any medications. Blood for cortisol determination was obtained with the subject in the supine position at 8:00 A.M. Two consecutive spirometric examinations that took place an average of 4.7 yr apart were employed in the analysis. Cross sectional analysis revealed a weak (p = 0.08) direct relationship between the basal plasma cortisol concentration and FEV1. The cortisol concentration and FVC appeared unrelated. Longitudinal analysis revealed a significant (p = 0.008) relationship between the plasma cortisol concentration and the rate of decline of FEV1 over the follow-up interval after adjustment for age, height, smoking status, and initial FEV1 in a multivariate regression model. This multivariate model predicts that subjects with cortisol concentration 1 standard deviation (23.3 ng/ml) below the mean would experience FEV1 decline 71.6 ml/yr greater than subjects with cortisol concentration 1 standard deviation above the mean. This difference was comparable to the estimated 69.5 ml/yr difference between current and never smokers. Cortisol concentration was unrelated to the rate of decline of FVC. The data suggest that physiologic concentrations of cortisol may modulate the process responsible for the deterioration of ventilatory function with aging. PMID- 8503545 TI - Performance characteristics and interanalyzer variability of PO2 measurements using tonometered human blood. AB - We performed a side-by-side comparison of the ability of four blood gas analyzers (IL-1312, Corning-178, AVL-995, and ABL-330) to measure PO2 across a wide range under controlled laboratory conditions. Samples of fresh whole human blood, tonometered with analytic quality gas, were prepared with partial pressures of oxygen from 0 to 283 mm Hg. Fifteen determinations were made at 16 levels of tonometric PO2 (tPO2) on each of the four blood gas analyzers. The bias, precision, and root mean squared error (RMSE) of the PO2 measurement relative to tPO2 were determined for each analyzer at each tPO2 level. Mean bias and precision across the range tested were 2.78 +/- 1.29 mm Hg (IL), -0.35 +/- 1.91 (Corning), 2.14 +/- 1.43 (AVL), and 3.00 +/- 1.47 (ABL). RMSE was 3.28, 2.61, 3.57, and 2.41 for IL, AVL, ABL, and Corning, respectively. Percent RMSE (RMSE/tPO2 x 100%), ranged from 0.9% (AVL at 75 mm Hg PO2 and IL at 283 mm Hg tPO2) to 9.1% (IL at 29 mm Hg tPO2). Three analyzers (AVL, ABL, and Corning) showed a statistically significant (p < 0.0001) correlation between RMSE and tPO2, and no correlation between percent RMSE and tPO2. This demonstrates that, for these instruments, accuracy is a function of the magnitude of the tPO2 value. IL did not show a significant correlation between RMSE and tPO2 but did demonstrate a significant negative correlation (r = -0.78, p > 0.001) between percent RMSE and tPO2, indicating that, for this analyzer, accuracy is not a function of tPO2. The differences in PO2 measurements between pairs of analyzers were also examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503546 TI - Cost effectiveness of noninvasive oxygen saturation measurement during exercise for the diagnosis of Pneumocystis carinii pneumonia. AB - We assessed (1) the sensitivity and specificity of exercise oxygen saturation measurement (EOS) for the diagnosis of Pneumocystis carinii pneumonia (PCP); and (2) the cost of introducing this indirect diagnostic test compared with that of standard diagnostic strategies for PCP. In a prospective study, 85 HIV-infected patients with suspected PCP underwent EOS, followed by induced sputum (IS) and bronchoalveolar lavage (BAL) if IS was negative for P. carinii. The prevalence of PCP was 0.22, the sensitivity of IS was 0.6, and its specificity was perfect. The cost ratios of IS to BAL and EOS to BAL were 0.1 and 0.2, respectively. A desaturation of three points was the best cutoff point, giving perfect sensitivity and a specificity of 0.77. The cost analysis showed that the introduction of EOS into diagnostic strategies for PCP is highly justified when the local prevalence is low. Exercise oxygen saturation measurement is simple and safe, and the results are available rapidly; its sensitivity is perfect and its specificity good. Its economic utility depends on its cost and the local prevalence of PCP in the test population. PMID- 8503547 TI - Physiologic responses and distribution of aerosolized surfactant (Survanta) in a nonuniform pattern of lung injury. AB - The underlying pattern of lung injury in patients with the adult respiratory distress syndrome (ARDS) may be nonuniform. The purpose of this study was to document whether a nonuniform pattern of lung injury influences treatment responses to aerosolized exogenous surfactant. Adult sheep underwent either total lung lavage (Tot Lav) or partial lung lavage (Par Lav) with saline, and they were subsequently mechanically ventilated for 90 min. Previous studies confirmed that this procedure induces acute lung injury. Partial lavage animals had their right upper lobe (RUL) protected from lavage by balloon obstruction of the RUL bronchus, and the occlusion was removed prior to the ventilatory period. Animals in both groups were then treated with either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) for a further 180 min. PaO2, PaCO2, and peak inspiratory pressure significantly improved for the Tot Lav-Neb Surf animals compared with pretreatment values (p < 0.01). There were no significant changes for the other three groups (Tot Lav-Neb Saline, Par Lav-Neb Surf, Par Lav-Neb Saline). Lobar distribution of aerosolized [3H]surfactant in lung tissue revealed that Par Lav-Neb Surf animals had approximately 50% of the total surfactant recovered from the RUL compared with approximately 20% recovery from the RUL in the Tot Lav-Neb Surf group. The preferential deposition of exogenous surfactant in the RUL of the Par Lav-Neb Surf group resulted in significantly less surfactant deposited in other injured regions of the lung (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503548 TI - Neutrophil elastase inhibitors, SC-37698 and SC-39026, reduce endotoxin-induced lung dysfunction in awake sheep. AB - Neutrophils have been implicated as important cellular mediators of the pulmonary dysfunction observed following endotoxemia in chronically instrumented awake sheep. Several areas of research suggest that neutrophil-derived proteases may be mediators of this dysfunction. We hypothesized that neutrophil elastase inhibitors would attenuate the effects of endotoxemia in sheep. To test this hypothesis, we studied the effects of two putative neutrophil elastase inhibitors, SC-37698 and SC-39026 (Searle, Skokie, IL), on endotoxin-induced lung dysfunction in awake sheep. Sheep were given intravenous neutrophil elastase inhibitor alone (20 mg/kg/h for 6 h), intravenous endotoxin (E. coli endotoxin, 0.5 microgram/kg over 20 min) 1 h after beginning the 6-h infusion of elastase inhibitor, or endotoxin 1 h after beginning a 6-h infusion of elastase inhibitor vehicle. SC-37698 attenuated the increase in lung lymph flow and lung lymph protein clearance, the alterations in lung mechanics, and the fall in white blood count. Qualitatively similar effects were seen with SC-39026. These data suggest the need for further research examining the role of protease-antiprotease interactions and the potential utility of neutrophil elastase inhibitors in acute lung injury like that observed in the adult respiratory distress syndrome (ARDS) in the human. PMID- 8503549 TI - Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor. AB - The total and differential cell counts of 135 bronchoalveolar lavages (BAL) in 48 heart-lung transplant (HLT) patients were compared with the histologic findings in concurrent transbronchial lung biopsies (TBBs). Counts of CD3+, CD4+, and CD8+ lymphocytes were recorded, and a semiquantitative assessment of HLA-DR and interleukin-2 receptor (IL-2R) expression was made on 29 occasions. There were five diagnostic categories: normal (n = 8), acute rejection (ALR) (n = 57), treated rejection (TR) (n = 19), infection (INF) (n = 24), and chronic rejection (CR) (n = 24). Total cell counts in INF were significantly higher than counts in all the other diagnostic groups. The highest BAL lymphocyte counts, significantly higher than in INF, were found in ALR because of increased CD8+ cells, exceeding 15% in 13 of 57 BALs. TBBs in ALR by contrast showed significantly increased numbers of both CD8+ and CD4+ cells. High dose corticosteroid treatment of ALR caused a fall in cellularity of BAL and TBB specimens but not always to values seen when patients were well. During INF and CR, significantly increased numbers of PMNs were seen in the BAL. HLA-DR and IL-2R expression was enhanced in cells of BAL and TBB in all complications. BAL can only supplement at present histologic examination of TBB in the diagnosis of complications after HLT. PMID- 8503550 TI - Clinical course of idiopathic pneumonia after bone marrow transplantation. AB - We describe the clinical course of idiopathic pneumonia diagnosed by lung biopsy after allogeneic marrow transplantation and the associations of clinical presentation with outcome. All allogeneic marrow transplant recipients with an open-lung biopsy at a single marrow transplantation research center between January 1983 and December 1988 who were without infection were reviewed as a case series (n = 41). Data were retrieved from clinical information routinely collected at the time of transplantation on all patients. The onset of pneumonia was 11 to 143 days after transplant (mean 35), and 93% of cases displayed diffuse pulmonary infiltrates. Overall in-hospital mortality was 71% (n = 29). The case fatality rate was 59% (n = 24): 13 patients (32%) died with progressive respiratory failure, and the other 11 fatalities (27%) died either with recurrent respiratory failure after initial improvement (n = 7) or from nonpulmonary causes without resolution of pneumonia (n = 4). Infection was a major complication and was present at autopsy in 11 of 16 cases (69%). Of 12 patients discharged from the hospital 6 died within 1 yr, most commonly with relapse of malignancy. Both receipt of total-body irradiation > 1,200 cGy and presence of acute graft-versus host disease were associated with an increased rate of resolution of pneumonia. The overall mortality of idiopathic pneumonia after allogeneic marrow transplantation is high, but less than one-third of patients die of progressive respiratory failure related to idiopathic pneumonia. Infection is commonly associated with death in marrow recipients previously diagnosed with idiopathic pneumonia by lung biopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503551 TI - Detection of mycobacterial antigens present in short-term culture media using particle counting immunoassay. AB - Particle counting immunoassay (PACIA) was compared with the BACTEC system for detecting mycobacterial growth after short-term culture and was used to identify M. tuberculosis. The latex particles were coated with polyclonal anti-BCG or with specific 2A1-2 monoclonal antibodies. Bottles containing nonradioactive Middlebrook 7H9 liquid medium and BACTEC 12B vials were inoculated with equal amounts of mycobacteria from four reference strains (M. tuberculosis, M. kansasii, M. avium, and M. xenopi). Using anti-BCG, PACIA detected mycobacterial antigens 3 to 6 days before the BACTEC system. M. tuberculosis was differentiated from the other mycobacteria using 2A1-2. Seventeen clinical samples were also studied. In the same 10, the two techniques detected mycobacteria, PACIA with anti-BCG after 9 days and BACTEC 1 to 5 days later. For 9 of the 10 samples, PACIA with 2A1-2 detected M. tuberculosis after 20 days, a result confirmed with the AccuProbe system. M. xenopi was biochemically identified in Specimen 10. Nonmycobacterial diseases were diagnosed in the 7 remaining unreactive specimens. We conclude that PACIA detects mycobacterial growth earlier than BACTEC and that M. tuberculosis can be distinguished from other mycobacteria in PACIA performed with specific monoclonal antibodies. PMID- 8503552 TI - Significant reduction of nonspecific bronchial reactivity in patients with Dermatophagoides pteronyssinus-sensitive allergic asthma under therapy with allergen-antibody complexes. AB - Thirty-nine asthmatic patients hypersensitive to Dermatophagoides pteronyssinus were treated for a total of 4 yr with injections of complexes made of allergen and autologous specific antibodies. The results obtained throughout the first 2 yr of a double-blind placebo-controlled trial have been published (1) and we now report the results of such therapy during an additional 2 yr. Three groups of patients had been defined: Groups A and B were comprised of patients treated with either "higher" doses of complexes (Group A) or "lower" doses (Group B), whereas Group C received the placebo preparation. Four injections of complexes were performed during the third yr and none during the fourth yr. The clinical benefit resulting from such injections was maintained until the end of the study, whereas medication intake, especially systemic or high doses of inhaled corticosteroids, was much reduced. Skin reactivity to allergen was significantly decreased in both treated groups. Bronchial provocation tests were carried out at 1-yr intervals with either allergen or acetylcholine (ACh). Reactivity to allergen inhalation was significantly decreased at each time point. Reactivity to ACh was significantly decreased at the end of Years 3 and 4. Fifty percent of treated patients who underwent bronchial challenges lost their bronchial reactivity to the highest concentrations of both allergen and ACh. A significant improvement in the basal lung function was observed in both treated groups. The long-term effects of immunotherapy with allergen-antibody complexes in allergic asthma patients thus include reduction in nonspecific bronchial reactivity. PMID- 8503553 TI - Water loss without heat flux in exercise-induced bronchospasm. AB - We identified inspired gas conditions that result in no net respiratory heat loss, an isenthalpic condition, but induce a mucosal loss of water. Inspired gas at 37 degrees C with 47 mm Hg water vapor pressure, 56 degrees C with 38 mm Hg; and 78 degrees C with 27 mm Hg has the same heat content as fully saturated air at body temperature. In four normal subjects hyperventilating at a minute ventilation of 30 times their FEV1 for 6 min, expired temperatures at the mouth averaged 39 degrees, 43 degrees, and 43 degrees C for the three conditions. Retrotracheal esophageal temperatures did not fall in any subject, thereby demonstrating the absence of significant airway cooling. Nine subjects with exercise-induced bronchospasm were tested under the same conditions. Baseline functions showed an FEV1 of 85 +/- 10% of predicted (mean +/- SD), FVC, 98 +/- 13% of predicted, and FEV1/FVC, 79 +/- 4% of predicted. The asthmatic subjects demonstrated postchallenge mean falls in FEV1 of 3.4%, 6.2%, and 10.1% for the three conditions, with bronchospasm increasing as the temperature of the inspired air increased (p = 0.001). The amount of respiratory water lost from the respiratory mucosa significantly correlated with the resultant bronchospastic response as measured by the fall in FEV1 (p = 0.017), but the net respiratory heat lost did not significantly correlate (p = 0.113). This study demonstrates that bronchospasm can be induced without significant respiratory heat loss or airway cooling and suggests that it is proportional to the amount of water lost from mucosal surfaces. PMID- 8503554 TI - Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. AB - The recent development of new beta 2-adrenoceptor agonists with a duration of action in excess of 12 h may change strategies in the treatment of bronchial asthma. This study aims at the direct comparison of the main representatives of this new class of drugs, formoterol (F) and salmeterol (S), in asthmatic patients over the course of 24 h. Twelve patients with mild bronchial asthma participated in a double-blind, randomized, placebo-controlled clinical trial. In a dose finding study we determined the protective and bronchodilating effects of 12 and 24 micrograms F aerosol vs 50 and 100 micrograms S 30 min after inhalation. In a 24-h study we investigated the effects of 12 micrograms F and 50 micrograms S on airway tone and responsiveness. Bronchial responsiveness was assessed as the dose of methacholine necessary to decrease FEV1 by 20%. In the dose-finding study, compared with placebo, all doses of F and S equally increased FEV1 (p < 0.003) and protected against inhaled methacholine (p < 0.0001). In the 24-h study 12 micrograms F and 50 micrograms S increased FEV1 and significantly protected against methacholine-induced bronchoconstriction up to 24 h (p < 0.05), compared with placebo. Phase and amplitude of the circadian variation of FEV1 and airway responsiveness were not affected. Clinically recommended doses of aerosolized F (12 micrograms) and S (50 micrograms) have a duration of action up to 24 h and are equally effective at bronchodilation and protection in acute experiments in patients with mild bronchial asthma. PMID- 8503555 TI - Factors associated with bronchial responsiveness to histamine in a population sample of adults. AB - The association of age, gender, number of eosinophils, area of residence, cigarette smoking, respiratory symptom prevalence, and FEV1 with the level of bronchial responsiveness was studied in a random sample of 2,216 subjects aged 15 to 72 yr. Subjects participated in the Dutch longitudinal study on chronic obstructive pulmonary disease. In 18 yr of follow-up, 5,012 observations were collected. Interviewers used a standardized questionnaire to assess the presence of respiratory symptoms. Bronchial responsiveness was measured by a histamine challenge test. Because multiple measurements within a subject are correlated, multivariate regression methods for correlated outcome were used. A greater number of eosinophils, skin test positivity, and living in a rural area (Vlagtwedde) were associated with increased responsiveness, independently of the level of FEV1 and the presence of respiratory symptoms. Older age was associated with increased responsiveness, and this was even more so in subjects with symptoms. Cigarette smokers were more responsive than nonsmokers, but this association was not significant if the level of FEV1 was taken into account. Hyperresponsiveness was more likely to be present if the amount of cigarettes smoked per day was greater. The level of responsiveness did not differ significantly between males and females. For the same degree of obstruction, however, expressed as the FEV1/VC ratio, males tended to be less responsive than females. The analyses were repeated using the dose-response slope as a continuous measure of responsiveness and by applying a method to adjust for censoring the responsiveness data. These analyses yielded identical results. PMID- 8503556 TI - Asthma mortality in California, 1960-1989. Demographic patterns and occupational associations. AB - We analyzed asthma mortality rates in California during the years 1960 to 1989. Sex- and race-specific rates were stratified by age group (0 to 4, 5 to 34, 35 to 64, and 65+ yr) and for all ages directly standardized to the 1970 U.S. age distribution. Observed and expected asthma deaths were also calculated by occupation for the period 1979 to 1981 among persons aged 16 to 64 yr using data from the California Occupational Mortality Study. Asthma mortality rates were strongly associated with increasing age, but no consistent differences were observed between men and women. Mortality rates among blacks under age 65 yr were two to four times the corresponding rate among whites between 1960 and 1989, but this difference was not observed for those over age 65. Asthma mortality rates were calculated for Hispanics and Asians from 1985 to 1989. In this time period the asthma mortality rate ratios for Hispanics were 0.4 to 0.8 compared with the age-stratified rates among whites, 0.1 to 0.2 times the black rates in age categories under 65, and 0.5 times the rate for blacks ages 65 and above. Asthma mortality rates among Asians under 65 yr of age were similar to rates for whites, but for Asians 65 yr of age and over the rate ratios for males and females compared with whites were 1.8 and 1.1, respectively. A decrease of approximately 50% in asthma mortality occurred from 1960 to 1970, and a marked increase occurred between 1975 and 1989.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503557 TI - Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma. AB - Patients with asthma generate increased amounts of reactive oxygen species (ROS) from peripheral blood cells and cells recovered by bronchoalveolar lavage (BAL). ROS produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. Although antioxidant defenses inhibit the changes produced by ROS, no data are available on local antioxidant defenses in asthma. The present study was designed to begin to explore these defenses by measuring superoxide dismutase (SOD) and catalase activities and total glutathione (GSH) levels in BAL fluid from normal subjects and patients with mild asthma. Baseline pulmonary function and methacholine bronchoprovocation tests were performed on all subjects. BAL was achieved by instilling five 20-ml aliquots of phosphate buffered saline in each of three lung segments. The fluids recovered from the first 20-ml aliquot and that from the next four aliquots were labeled bronchial and alveolar fluid, respectively. Patients with asthma had a lower FEV1 (p < 0.005), less BAL fluid recovered (p < 0.05), and an increased percentage of bronchial eosinophils (p < 0.05). There were no differences in BAL total cell count or protein concentration. Catalase activity was not consistently detected in the unconcentrated BAL fluid from either group. SOD activity was found in both bronchial and alveolar samples, but it was similar in the two groups of subjects. The GSH concentration in bronchial fluid was higher in the patients with asthma (23.9 +/- 6.2 vs 13.0 +/- 1.8 microM/mg protein; p < 0.05); a similar trend was seen in the alveolar fluid (36.5 +/- 9.4 vs 23.3 +/- 3.0 microM/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503558 TI - Physiologic significance of epithelial removal on guinea pig tracheal smooth muscle response to acetylcholine and serotonin. AB - We studied the modulatory effect of airway epithelium on guinea pig tracheal smooth muscle (TSM) contraction. Isometric force was measured in vivo before and after removal of the tracheal epithelium. In parallel studies, TSM contraction was also measured isometrically in epithelium-intact and epithelium-denuded TSM strips in vitro. Epithelial removal in vivo did not alter the contractile response of TSM to acetylcholine (ACh) or serotonin. In nine guinea pigs, active tension (AT) caused by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force per longitudinal length of the segment (g/cm) in the presence of epithelium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (confirmed histologically) (p NS). The threshold response to ACh was also unchanged (-8.0 +/ 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm with an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial removal in vivo (p NS). Epithelial removal in vitro increased the sensitivity of TSM contraction to ACh when the data were expressed as the percentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epithelium intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503559 TI - Epithelium removal and peptidase inhibition enhance relaxation of human airways to vasoactive intestinal peptide. AB - In this study we evaluated the role of epithelial versus subepithelial peptidases in the responses of isolated peripheral and central human airways to VIP. Human airways were obtained at thoracotomies (n = 8) and studied in organ baths. Intact or epithelium-denuded strips of central and peripheral airways were incubated with or without a cocktail of peptidase inhibitors containing phosphoramidon (2.5 micrograms/ml), leupeptin, aprotinin, captopril, soybean trypsin inhibitor (all 20 micrograms/ml), and bestatin (2.8 micrograms/ml). After precontraction with histamine (5 x 10(-6) M), cumulative concentration-response curves to VIP (10( 10) to 10(-7) M) were obtained. Both intact central and peripheral airways showed only minor relaxations to VIP irrespective of the precontraction level. Removal of the epithelium and addition of peptidase inhibitors additively increased the sensitivity (> 20-fold) and maximal response to VIP in both central and peripheral airways. We conclude that (1) VIP relaxes both central and peripheral human airways but only in the absence of epithelium and/or the presence of peptidase inhibitors, and (2) both epithelial and subepithelial peptidases are important in the inactivation of VIP in human airways. PMID- 8503560 TI - Long-term effects of protriptyline in patients with chronic obstructive pulmonary disease. AB - Protriptyline has been shown to improve nocturnal and diurnal hypoxemia in patients with chronic obstructive pulmonary disease in short trials. We prospectively evaluated the long-term effects of protriptyline on pulmonary functions (lung volume and expiratory flow, arterial blood gases) and sleep characteristics (sleep architecture, nocturnal desaturations) in these patients. Sixteen patients previously studied before and after 10 wk of protriptyline treatment were reevaluated after a long-term follow-up (range, 18 to 63 months); the results of those still receiving protriptyline were compared with those who stopped using the drug. Nine patients were still receiving protriptyline at the follow-up visit (10 to 20 mg/day at bedtime), and seven had stopped using the drug because of side effects. These two groups of patients did not differ in their follow-up duration, age, weight, pulmonary functions, and sleep architecture, or in their protriptyline-induced changes in diurnal arterial blood gases and nocturnal desaturation. At the follow-up visit, arterial blood gas determinations had returned to baseline values in all patients no longer receiving protriptyline. In the other group there was no difference between the baseline and follow-up PaO2 values (57.4 +/- 3.4 and 57.0 +/- 1.2 mm Hg, mean +/- SEM). There was no difference in the results of arterial blood gas determinations and pulmonary function tests obtained at the different visits between the two groups. Sleep architecture differed between these two groups, REM sleep time being shorter and the slow-wave sleep time being longer in the patients still receiving the drug. In both groups the cumulative SaO2 curves were similar to those obtained at baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503561 TI - Mast cells' contribution to the fibrosing alveolitis of the scleroderma lung. AB - Fibrosing alveolitis is frequently seen in scleroderma. Although usually causing progressive symptomatology, it may be found in patients reporting no respiratory symptoms. Mast cells may play a role in the pathogenesis of skin fibrosis in scleroderma. We determined the mast cells and other cellular content, as well as measuring the inflammatory mediators in the bronchoalveolar lavage fluid (BALF) in 17 scleroderma patients and nine control subjects to correlate BALF features with fibrosing alveolitis as determined by lung function testing and high resolution computed tomographic scans. Bronchoalveolar lavage cells were enumerated after May-Giemsa-Grunwald (MGG), alcian blue, and safranine blue staining. Histamine, tryptase, eosinophil cationic protein, hyaluronic acid, and neutrophil-specific myeloperoxidase were measured by radioimmunoassay. In comparison with normal subjects the BALF of scleroderma patients showed an increased percentage of mast cells (p < 0.002, Mann-Whitney U test), and increased levels of histamine (p < 0.005), tryptase (p < 0.02), and hyaluronic acid (p < 0.004). The BALF of the eight scleroderma patients with an abnormal chest X-ray had a significantly greater number of mast cells (p < 0.04, Mann Whitney U test), and significantly higher levels of histamine (p < 0.03, Mann Whitney U test) and tryptase (p = 0.02, Mann-Whitney U test) than the nine scleroderma patients with a normal chest X-ray. This study demonstrates the importance of mast cells and mast-cell activation in the pathogenesis of the fibrosing alveolitis of scleroderma. PMID- 8503562 TI - Changes in cell population and tumor necrosis factor, interleukin-6, and interleukin-8 in malignant pleural effusions after treatment with intrapleural tetracycline. AB - To evaluate the changes in cellular components and cytokine levels (tumor necrosis factor, interleukin-6 and IL-8) before and after intrapleural tetracycline (TC) injection, we evaluated 10 patients with malignant pleural effusion. Differential cell counts in the pleural fluid were obtained using cytocentrifuge preparations. Mononuclear cells from pleural fluid, collected before intrapleural injection of TC, on Day 4, and Days 10 to 14 after TC injection, were stimulated either with phytohemagglutinin (PHA) or PHA plus phorbol myristic acetate. The production of tumor necrosis factor (TNF) and IL-8 was measured. In addition, IL-6, IL-8, and TNF from serial collections of pleural fluid in these patients were measured by RIA or ELISA. The main inflammatory cells in pleural effusions before therapy were lymphocytes and mononuclear cells, but neutrophils predominated after TC injection. IL-6, IL-8, and TNF were markedly increased on Day 4 after TC intrapleural injection and then decreased to baseline levels on Day 14. The results suggest that TC intrapleural injection induces the release of cytokines (IL-6 and TNF), which are markers of an inflammatory response, and releases IL-8, which attracts neutrophils into the pleural space, which may be the mechanism of the sclerosing effect of TC. PMID- 8503563 TI - Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung. AB - We examined the effect of activated alveolar macrophages (AM) on airway responsiveness to muscarinic stimulation in 33 adult Sprague-Dawley rats. An isolated-perfused lung preparation was used to ensure precise and uniform delivery of cells into peripheral airways. The bronchoconstrictor response to acetylcholine (ACh) delivered into the pulmonary arterial circulation was augmented in 8 rats after infusion of 3 x 10(6) AM activated with 10(-6) M f-met leu-phe and 5 micrograms/ml of cytochalasin B. Lung resistance (RL) caused by 10( 6) mol ACh increased 2.5-fold from 0.10 +/- 0.004 cm H2O/ml/s before infusion of activated AM to 0.35 +/- 0.05 cm H2O/ml/s after infusion of activated AM (N = 8; p < 0.05); the response to ACh was not augmented after infusion of nonactivated AM (N = 7) or vehicle control (N = 6). Baseline RL before ACh was similar in all three groups (p NS). Perfusion with activated AM also significantly increased the wet/dry (W/D) lung weight ratios (7.1 +/- 0.5) compared with nonactivated AM (5.2 +/- 0.1) or vehicle control (5.5 +/- 0.3) (p < 0.05 versus either nonactivated AM or vehicle control). A63162, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, completely inhibited augmentation of bronchoconstrictor responses to ACh caused by activated AM and also completely attenuated the increase in W/D lung weight ratios. A highly significant (p < 0.01) correlation (R = 0.76) between W/D lung weight ratios and RL was observed after 10(-6) mol ACh (the greatest dose of ACh administered). Baseline RL was equivalent for all groups before and after infusion of cells or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503564 TI - Effect of aging on metabolic respiratory control in sleeping dogs. AB - We examined the effects of aging on the metabolic respiratory control system by measuring changes with time in steady-state minute volume of ventilation (VI), alveolar carbon dioxide pressure (PACO2), and ventilatory and arousal responses to hypercapnia and hypoxia during slow-wave sleep (SWS). Studies were performed longitudinally in six healthy dogs over a span of 3 to 7 yr, corresponding biologically to 12 to 24 human yr. In each of the dogs aging was associated with a decrease in steady state VI during SWS, from 6.53 +/- 1.08 (mean +/- SEM) to 5.56 +/- 0.90 L/min (p < 0.01), and with an increase in PACO2 from 36.2 +/- 1.0 to 38.5 +/- 1.1 mm Hg (p < 0.01). However, ventilatory and arousal responses to hyperoxic hypercapnia (four dogs) remained unchanged. In contrast there was a decrement in the response of VI to isocapnic hypoxia during SWS (five dogs), from 1.22 +/- 0.12 to 0.70 +/- 0.07 L/min/% fall in arterial O2 saturation (SaO2) (p < 0.02), and a decrease in arousal SaO2, from 83.3 +/- 3.2 to 73.5 +/- 2.3 percent (p < 0.001). The findings indicate that aging is accompanied by impairment of ventilatory and arousal responses to hypoxia during SWS, and point to a specific effect of aging on the carotid-body chemoreceptors, as opposed to the brainstem respiratory controller or the ventilatory pump. PMID- 8503565 TI - Determinants of continuous positive airway pressure level for treatment of obstructive sleep apnea. AB - The purpose of this study was (1) to examine the factors that account for the variability in continuous positive airway pressure (CPAP) levels required to abolish obstructive sleep apnea (OSA) in patients with this disorder, and (2) to examine the feasibility of predicting the lowest effective pressure (CPAPmin) from simple anthropometric and polysomnographic variables easily available in all patients considered for home CPAP therapy. To accomplish these tasks we studied a group of 208 patients with OSA all of whom were treated with nasal CPAP at home. We first analyzed a model set of 38 patients all of whom had at least two polysomnographic studies (the diagnostic one and a subsequent one to determine CPAPmin for home use), anthropometric measurements (including body mass index, neck circumference, and waist circumference), pulmonary function measurements (lung volumes, airways resistance, and flow-volume curves), pharyngeal and glottic cross-sectional areas at functional residual capacity and residual volume, and nasal airflow resistances. We compared patients requiring CPAP > 10 cm H2O with those who required CPAP < 5 cm H2O. The high CPAP group was characterized by a greater degree of obesity, more severe sleep apnea, and more collapsible pharynx. Multiple linear regression analysis using principal components and Mallows C(P) statistics revealed that the optimal set of predictors for CPAPmin consisted of only three variables: apnea/hypopnea index, body mass index, and neck circumference. This model accounted for 76% of the variability in CPAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503566 TI - Surface phenotype of Langerhans cells and lymphocytes in granulomatous lesions from patients with pulmonary histiocytosis X. AB - Pulmonary histiocytosis X (HX) is a disorder characterized by the presence of granulomas in which Langerhans cells (LC) and lymphocytes are abundant. Although the pathogenesis of pulmonary HX remains unknown, an uncontrolled immune response initiated by LC, which are potent antigen-presenting cells in vitro, may play an important role. To further characterize LC and lymphocytes present in granulomas from these patients, we used immunohistochemical techniques and monoclonal antibodies to evaluate the surface phenotype and electron microscopy (EM) to seek evidence for close interactions between both cell types in these lesions. In all samples, HX granulomas contained large numbers of strongly positive CD1a cells in which typical Birbeck granules were identified by EM. The number of Birbeck granules in LC from HX granulomas was strikingly increased compared with that in LC in the bronchioles of normal subjects. Furthermore, unlike normal LC, essentially all LC in HX granulomas expressed CD4 antigens and were strongly positive for CD1c. Lymphocytes infiltrating HX granulomas were almost entirely CD3+ T cells and were mainly CD4 positive (CD4/CD8 ratio 3.7 +/- 1.3). These T lymphocytes expressed almost exclusively alpha/beta T cell receptors, and gamma/delta T cells were rarely observed (< 5% of CD3+ cells). In areas of lymphocytic infiltration, close differentiated contacts between LC and lymphocytes were observed by EM in all samples. These results demonstrate that interactions between activated LC and CD4+ T lymphocytes are prominent in early HX granulomas and support the idea that an immune response in which LC serve as accessory cells is involved in the pathogenesis of this disorder. PMID- 8503567 TI - Involvement of tachykinins in pentamidine-induced airway constriction and microvascular leakage in the guinea pig. AB - We investigated the effects of aerosolized pentamidine isethionate on airway constriction and microvascular leakage in the guinea pig, and the role of tachykinins in these abnormalities. The bronchoconstrictor response to pentamidine was determined in anesthetized, tracheotomized and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized pentamidine (5 to 30 mg/ml; 60 breaths). Respiratory system resistance was measured by the occlusion method. Airway microvascular permeability was evaluated by measuring the Evans blue dye concentration in the trachea and main bronchi. Aerosolized pentamidine caused a concentration-related increase in respiratory system resistance that was prevented by pretreatment with 50 mg/kg capsaicin given subcutaneously 2 wk before pentamidine and was significantly reduced by pretreatment with 1 mg/kg morphine given intravenously. Pretreatment with 10(-4) M aerosolized phosphoramidon (90 breaths) significantly enhanced the bronchoconstrictor response to pentamidine. Aerosolized pentamidine (50 mg/ml; 90 breaths) increased airway microvascular permeability, as the Evans blue dye concentration was 72.6 +/- 3.7 ng/mg tissue in guinea pigs aerosolized with pentamidine versus 34.2 +/- 3.5 ng/mg tissue in the controls. Capsaicin pretreatment inhibited the increase in microvascular leakage induced by pentamidine. Pretreatment with 5 mg/ml aerosolized albuterol (90 breaths) prevented the bronchoconstrictor response to pentamidine but failed to prevent the pentamidine-induced increase in microvascular permeability. Atropine did not modify the bronchoconstrictor response to pentamidine. These results indicate that in the guinea pig, pentamidine isethionate induces bronchoconstriction and airway microvascular leakage, which are mediated by tachykinins released from sensory nerves. Albuterol, which is used in humans to prevent bronchoconstriction, does not seem able to prevent airway edema. PMID- 8503568 TI - Lectin-detectable glycoconjugate profile of the tracheal secretions and epithelial glycocalyx in sheep. Effect of muscarinic stimulation. AB - Reflex mucus secretion in the airways serves a defense function that includes the binding of bacteria to mucus glycoconjugates thereby preventing bacterial adherence to the epithelium. We therefore compared the lectin-detectable glycoconjugate profile of the epithelial glycocalyx and luminal secretions under baseline conditions and after muscarinic receptor stimulation in the sheep trachea. The sheep were intubated with a double-balloon nasotracheal tube to create a tracheal chamber for collection of secretions. After an initial lavage of the chamber to clear it of secretions, the sheep received an intravenous injection of normal saline, 0.5 mg/kg pilocarpine, or 0.5 mg/kg pilocarpine after pretreatment with 0.2 mg/kg atropine. Tracheal lavage was repeated 2 h later, and the sheep were then killed. An enzyme-linked lectin assay and lectin histochemistry were used to characterize glycoconjugate residues in tracheal secretions and in the apical epithelial glycocalyx, respectively. Eight different lectins were used to detect N-acetyl galactosamine, alpha-galactose, alpha galactose-N-acetyl galactosamine, beta-galactose, beta-galactose-N-acetyl galactosamine, alpha-fucose, alpha-glucose, alpha-mannose and alpha-(2-3)sialyl residues. After normal saline, reactivity was present for all glycoconjugates in secretions and in the glycocalyx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503569 TI - Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids. AB - The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action. PMID- 8503570 TI - Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. AB - Elastinolytic enzymes derived from alveolar macrophages (AM) are considered to play an important role in the development of emphysema associated with cigarette smoking. In this study, the enzyme activity and mRNA expression of cathepsin L were quantitated in AM and bronchoalveolar lavage (BAL) fluid obtained from current smokers and compared with those from nonsmokers. Activity was measured with the synthetic substrate Z-Phe-Arg-MCA combined with a novel cathepsin B inhibitor, CA-074. We found that the specific activity of cathepsin L was significantly elevated in BAL cells from smokers (7.1 +/- 0.7 mumol/mg protein/h, mean +/- SEM) compared with cells from nonsmokers (2.9 +/- 0.3) (p < 0.01). The expression of cathepsin L mRNA in BAL cells as determined by dot-blot analysis was also higher in BAL cells from smokers, which was comparable to the increase in the enzyme activity. About 5 to 6% of the specific activity of cathepsin L in BAL cell lysates was detected in unconcentrated BAL fluid; specific activity was also significantly higher in samples from smokers (0.38 +/- 0.04 mumol/mg protein/h) than from nonsmokers (0.14 +/- 0.02). In addition, procathepsin L (42 kD) and the mature form of cathepsin L (33 kD) were demonstrated in BAL fluid by immunoblot analyses. These data suggest that cigarette smoking induces mRNA expression and the synthesis of cathepsin L in AM and the release of procathepsin from AM into extracellular milieu. Furthermore, increased activity levels of cathepsin L in extracellular compartments may contribute to the proteolysis of elastin in the process of lung destruction associated with cigarette smoking. PMID- 8503571 TI - Effects of ozone and neutrophils on function and morphology of the isolated rat lung. AB - Since whole-animal studies suggest that neutrophils play a role in ozone-induced impairment of pulmonary function and increases in airway reactivity, this study was designed to study more precisely the interaction of neutrophils and ozone using the isolated perfused rat lung. Sprague-Dawley rat lungs (n = 60) were ventilated for 3 h with 95% air and 5% CO2 alone or mixed with 1 ppm ozone and perfused with buffer alone or with neutrophils (8 x 10(7)). RL, Cdyn, Ppa, airway reactivity to methacholine, lung/body weight, bronchoalveolar lavage fluid (BALF) protein concentration, and airway lesions were analyzed using a two-way GLM or Kruskal-Wallis test (p < or = 0.05 significant). Both ozone and neutrophils increased RL and decreased Cdyn. Ozone but not neutrophils increased airway reactivity to methacholine. Neutrophils but not ozone increased lung weight/body weight and BALF protein concentration. Ozone damaged airway epithelium. In distal bronchioles, neutrophils enhanced this damage. We conclude that (1) ozone impaired pulmonary function, increased airway reactivity, and damaged airway epithelium without causing measurable microvascular leak; (2) neutrophils impaired pulmonary function, probably a result of microvascular leak, but did not change airway reactivity or damage airway epithelium; and (3) neutrophils had no effect on ozone-induced airway reactivity but had an additive effect on ozone induced pulmonary function impairment and a synergistic effect on ozone-induced airway epithelial injury. PMID- 8503572 TI - Expression of tumor necrosis factor-alpha gene in alveolar macrophages from patients with the adult respiratory distress syndrome. AB - The adult respiratory distress syndrome (ARDS) is a complex syndrome in which pathogenesis is multifactorial. TNF-alpha, known to be pivotal in tissue damage, has been shown to have high levels in blood and alveolar fluid in ARDS. The identification of the cells responsible for this production in the alveolar milieu has not yet been reported. In order to evaluate the TNF-alpha gene expression in ARDS we have analyzed by in situ hybridization, using RNA probes, alveolar macrophages (AM) obtained by BAL from seven patients with ARDS, eight patients with miscellaneous respiratory diseases, and three control patients. In freshly collected AM from patients with ARDS, 66 +/- 14.5% cells expressed the TNF-alpha gene without in vitro stimulation. This TNF-alpha expression does not result from the BAL procedure itself since only a few unstimulated control AM contained TNF-alpha mRNA transcripts. TNF-alpha expression in AM is not restricted to patients with ARDS since it has also been observed in miscellaneous respiratory diseases; however, this expression is a constant feature in ARDS. These results demonstrated the major role of AM in the intra-alveolar production of TNF-alpha, and they point out the necessity in ARDS for a specific intra alveolar therapy. PMID- 8503573 TI - Small bore nozzle extensions to improve the delivery efficiency of drugs from metered dose inhalers: laboratory evaluation. AB - Metered dose inhalers (MDIs) are frequently used to supply aerosolized drugs, particularly bronchodilators, to the tracheobronchial tree of patients with endotracheal tubes in the intensive care unit or in the operating room. The efficiency of delivery to the lungs of agents such as the beta 2-adrenergic agonists is known to be low. In an in vitro model, we evaluated a means of improving the delivery of drug released from an MDI beyond the distal tip of the endotracheal tube. Extensions of the MDI nozzle were fashioned from modified intravenous catheters or sections of small bore polyethylene tubing. A model trachea/carina was constructed and suspended above a collecting device. An albuterol MDI was actuated through the nozzle extension and into the model airway. We measured the quantity of albuterol deposited in the nozzle extension, in the trachea/carina and in the distal collecting device. Particle size distribution was determined with a cascade impactor. The results indicate an inverse relationship between the quantity of drug delivered distally and the inner diameter of the nozzle extension, with a marked increase in delivery for an inner diameter < 1 mm. Ninety percent of the actuated dose from the MDI exited a 0.76-mm inner diameter nozzle extension. From 20 to 30% of the nominal MDI dose was recovered from the distal collector, 70% of which deposited in the particle size range of 1 to 5 microns. Deposition in the trachea/carina was high, but this was reduced by introducing a flare in the tip of the nozzle extension, which did not affect the dose reaching the distal collector.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503574 TI - Thrombolysis for life-threatening pulmonary embolism 2 days after lung resection. AB - Early postoperative severe pulmonary embolism is usually considered an indication for surgical embolectomy because thrombolytic agents cannot be used. Severe pulmonary embolism was diagnosed 2 days after lung resection in two patients, including one with hypercapnia during spontaneous breathing, perhaps a unique feature of massive embolism on a single lung. Although emergency surgical embolectomy was available, both patients were given a bolus infusion of thrombolytic agents, with an immediate (within 1 h) clinical and hemodynamic improvement and a favorable outcome despite delayed major bleeding in one patient. The reported data and an analysis of the available literature support the view that recent surgery should be considered a relative rather than absolute contraindication to thrombolysis and that decision making in this setting should be based on a careful case-by-case evaluation of the expected benefits and risks of the various available treatments. PMID- 8503575 TI - Pulmonary sarcoidosis and corticosteroids. PMID- 8503576 TI - NHLBI workshop summary. Idiopathic pneumonia syndrome after bone marrow transplantation. PMID- 8503577 TI - Bronchoalveolar lavage cellularity: the distribution in normal volunteers. PMID- 8503579 TI - [Childhood lead poisoning in Asturias]. AB - We have determined the blood lead levels of 1,242 children, from newborn to 14 years old, and 79 young mothers in a period of 10 months in Asturias (Spain). All of them were selected at random among those who consulted one of the three main hospitals in Asturias, but none were diagnosed as lead poisoning. We have found a mean blood lead level of 22.11 micrograms/dl; 23.55% had high levels (= 25 micrograms/dl). Sex was not significantly associated with blood lead levels either in the whole sample or in different age groups. Blood lead level increases rapidly from birth (19.3 micrograms/dl) to the age of one year (23.3 gamma/dl), fluctuating around this level until the age of 7. Then it declines with age until adolescence (19.6 micrograms/dl). From October (25.5 micrograms/dl) to July (20.9 micrograms/dl) the decrease in lead blood level was statistically significant. No difference has been found between urban and rural population. The decree of urbanization has not been found significant. The mean blood lead level in the mothers was 20.5 micrograms/dl. PMID- 8503578 TI - [Enteral nutrition in pediatrics]. PMID- 8503580 TI - [Survey of arterial blood pressure in children and adolescents in the population of Guadasuar]. AB - Five hundred seventy-seven children (301 boys and 276 girls) from Guadasuar, whose blood pressure (BP) was taken in 1984, were reexamined over a three year period. The second of three BP readings, the most physiological, was used for the study. Among the boys, there was an increase in the systolic BP up to 16 years of age. The diastolic BP increased up to 12 years of age. For the girls, there was an increment of the systolic and diastolic BP us to 13 years of age. Our results, especially the diastolic readings, are higher than those of Sanchez (Spain) and of the Task Force (USA). The BP value at puberty could be important for the detection of future hypertension cases. PMID- 8503581 TI - [Correlation of arterial tension in the child population of Guadasuar]. AB - A longitudinal study of blood pressure (BP) in children from Guadasuar was undertaken in 1984 and 1987. The subjects included 577 children from 5 to 14 years of age. The regression analysis for systolic BP was r = 0.34 (p < 0.00000) (r = 0.38 in males and 0.30 in females). The diastolic BP was not significant. The tracking was studied for 84 cases detected in 1984 with BP values in the 95th percentile or above (for age and sex). In 1987, only 17 cases (20.2%) remained in this classification. This trend towards the normalization of BP as time progressed, and the low correlations found suggest that there is no predictability for high BP with only one measurement of BP. PMID- 8503582 TI - [Percutaneous balloon valvotomy in neonatal obstructive cardiopathy. II. Critical aortic valve stenosis]. AB - Percutaneous balloon aortic valvotomy using one or more balloons in sequential approach was attempted in 11 non selected neonates with critical aortic valve stenosis. The procedure was complete in 9 (81%), and they represent the study group with a mean age of 19 days. Using a balloon/annulus ratio of 0.86, the transvalvar gradient decreased from 49 to 25 mmHg, and left ventricular systolic pressure fell from 112 mmHg to 96 mmHg (p < 0.01, respectively). Fifty-five percent (5/9) of the patients developed a new aortic regurgitation, only one with grade 3. The maximal instantaneous Doppler gradient recorded in 7 neonates before and after valvotomy dropped from 67 to 35 mmHg (p < 0.01); while the left ventricular shortening fraction increased from 15 to 31% (p < 0.01). The Doppler gradient was correlated with the left ventricular shortening fraction (r:0.72) and the aortic regurgitation with the balloon/annulus ratio (r:0.82). The balloon pulmonary valvotomy was unsuccessful in 2 neonates (22%), both with hypoplastic left ventricle, both of which died in the operating room. Echocardiographic features of reestenosis were not found in the follow-up period (14 +/- 10 months); only one patient may need a future surgical intervention because significant aortic insufficiency. The pulmonary balloon valvotomy is a safe and effective therapy that must be used as the first step in the management of neonates with critical aortic stenosis in absence of hypoplastic left ventricle. PMID- 8503583 TI - [Preliminary results of a therapeutic program for childhood obesity in primary health care]. AB - The high prevalence of childhood obesity in our society, its adverse consequences in the psychosocial development of the child, together with its risk of persistence into adulthood, prompted us to carry out this treatment program in our Primary Care Unit. It is based fundamentally on four aspects: diet, physical exercise, psychological and family support. Thirty children, between 4 and 14 years of age, were controlled for 11 months. These children's personal and family characteristics, their habits and psychological aspects were described. An average reduction of the IMC of 2.50 was obtained. The best results were obtained in children with two or more siblings, with a good adherence to the diet and with adequate family support. Sex, obesity of other family members, initial age, previous habits, etc., were not found to be influential. The importance of prevention and family collaboration is emphasized. PMID- 8503584 TI - [Efficiency of psychotherapeutic methods in childhood asthma]. AB - The present study shows that the psychological interventions improve the results obtained with the traditional medical treatment in the management of asthmatic patients. A sample of 39 asthmatic children was selected. There was a significant improvement of the variables considered (emergency department consultations, number of acute episodes and days of illness), after psychological therapies were applied. We conclude that psychological interventions can be a useful complementary treatment of the results obtained with the pharmacological therapeutic. PMID- 8503585 TI - [Levels of maternal anxiety and their use in pediatric primary health care]. AB - Of a total population of a pediatric office of the Zaidin South Health Care Center, all of the mothers that were frequent users (69) were chosen and compared with a random sample of normal users (82). Both groups carried out the anxiety scale STAI. Significant differences were found in that the high users have greater levels of anxiety about trait (p = 0.0003), as well as state (p = 0.000). The high levels of anxiety of trait are associated with being a house wife, having a child with a chronic illness, non maternal lactation, low levels of studies, health education and family income. Family income was the variable with the greatest association with the anxiety of trait (multiple regression). When we took into consideration the variables of predisposition, availability and ease of use, the maternal anxiety continued to have a significant influence. We point out the importance of maternal anxiety in the high frequency of pediatric health care use and we underline the modifiable characteristics of the anxiety factor, and therefore the possibility of reducing the high use of health care services addressed. PMID- 8503586 TI - [The Navarra study. Prevalence of arterial hypertension, hyperlipidemia and obesity in the infant-child population of Navarra. Association of risk factors]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, 5,829 children were studied. These children, of both sexes, were between 4 and 17 years of age and were selected at random from the public and private school population in Navarra. The prevalence of hypertension (HT) was 7.17 +/- 0.34%, hyperlipemia (LDL/HDL > 2.2) 15.70 +/- 0.49% and obesity (Quetelet I) 3.96 +/- 0.26%. Of the children and adolescents in Navarra 23.68% show some of these three associated risk factors. Obesity was significantly associated with HT and hyperlipemia, measured by LDL/HDL > 2.2 (but not when defined by cholesterol > 200 mg/dl). This association was greater when the pathology was defined by the Quetelet Index, rather than by the skinfold thickness. Hypertension was not associated with hypercholesterolemia (defined as LDL/HDL > 2.2). The association with hyperlipemia (measured by LDL/HDL) disappeared when the obesity effect was eliminated. It is deduced from these factors that if we don't take preventative health measures, the present children and adolescents from Navarra will suffer a high cardiovascular morbi-mortality when they become adults. PMID- 8503587 TI - [Guide for the prevention of renal diseases during and after childhood]. AB - Kidney disease Prevention in childhood can be made from three levels. In the first level or Primary Prevention one must prevent kidney disease taking steps for "Kidney Health" promotion: environmental factors, nourishing, sanitary education and preventive pediatrics. Secondary Prevention lies in the correct diagnostic during first years in life and in a suitable treatment of the kidney diseases, especially in children to have a kidney failure risk: obstructive uropathy and vesicoureteral reflux. Tertiary Prevention deals with aggravating factors in an established Kidney chronic failure, and its prevention includes: normoproteic diet, phosphorus restriction, arterial hypertension control and nutritional and pharmacological steps to reduce the hyperlipidemia. PMID- 8503588 TI - [Trisomy 9p in congenital cardiopathy]. PMID- 8503589 TI - [Use of metronidazole in four cases of methyl-malonic acidemia]. PMID- 8503590 TI - [Hereditary angioedema. Diagnosis and treatment during childhood]. PMID- 8503591 TI - [Intrathoracic kidney in infancy: apropos of a case]. PMID- 8503594 TI - [Unusual skin manifestation of malformation of the thyroglossal duct]. PMID- 8503593 TI - [Infectious endocarditis in the course of pneumococcal meningitis: apropos of a case]. PMID- 8503592 TI - [Neonatal extralobar pulmonary sequestration. Diagnostic arteriography through the umbilical artery]. PMID- 8503595 TI - [Severe theophylline poisoning in an infant: management in a pediatric emergency care unit]. PMID- 8503596 TI - [Pseudogonococcal ophthalmia neonatorum induced by beta-lactamase positive Branhamella catarrhalis. Report of a case]. PMID- 8503597 TI - [HIV infection in infancy and childhood. Report of the second Spanish multicenter study (1991). Expert Committee on Pediatric AIDS]. PMID- 8503598 TI - [Neuroblastoma. Results of protocol N-I-87]. PMID- 8503599 TI - [The pediatrician and early detection of hyperphenylalaninemia. Study Group on Hyperphenylalaninemia)]. PMID- 8503600 TI - [Systemic diseases treated by corticoids, plasma exchange and cyclophosphamide: infectious complications and lymphopenia]. AB - The sporadic observation of pneumocystosis in patients suffering from systemic diseases led us to investigate the role of treatment-induced lymphopenia, affecting in particular CD4 cells. We report the results of a retrospective study on 16 patients in whom infectious complications were sought and correlated with the number of lymphocytes. PMID- 8503601 TI - Interview with Norman Talal. What is going to happen tomorrow as far as Sjogren's syndrome is concerned? PMID- 8503602 TI - [Cardiac complications of radiotherapy]. PMID- 8503603 TI - [Epileptic seizures following cerebrovascular complications]. PMID- 8503604 TI - [Malaise and its cost: the cost effectiveness of complementary tests]. AB - A study of 200 patients hospitalized in the Internal Medicine ward for malaise enabled us to specify several clinical features and to estimate the cost of this disorder. Clinical data from our investigation showed that the mean age of patients was 60 +/- 1.7 years, the women were older than the men, and age is an important parameter for orienting examinations which affects the length of hospitalization and increases with it. Among the etiological diagnoses of malaise, the systematic search for orthostatic hypotension is extremely important: it was responsible for 22 of the malaises of which only half were diagnosed in the emergency room. In addition, 12% of our series of malaises were medication-associated. The 200 patients represent 1,300 hospital-days at a total cost of 2,273,000 FF (congruent to US$454,600), and an average cost of 11,660 FF (congruent to US$2330) per malaise, of which 730 FF (congruent to US$145) was paid for complementary examinations. Thus it appears that the "hotel accommodations" part of the bill is the major element. All the complementary examinations ordered during the etiological search do not provide the same information and cost-benefit analysis showed that several simple tests, i.e., ECG, blood-sugar level, blood electropherogram and dosage of toxic substances, led to approximately 75% of the diagnoses; more sophisticated tests, e.g., cerebral computed-tomography scanning, Holter ECG or echocardiography, did not concern more than 25% of the malaises studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503606 TI - [Autoimmunity and AIDS]. PMID- 8503605 TI - [Mechanism of tumor hypercalcemia]. PMID- 8503607 TI - The current status of AIDS in Asia. PMID- 8503608 TI - [Human immunodeficiency virus infection and the thyroid tests]. PMID- 8503609 TI - [Provisory conclusions apropos of the prevention trials of opportunistic infections supported by ANRS (National Research Agency)]. PMID- 8503610 TI - [Results of the final analysis of the PRIO trial]. PMID- 8503612 TI - [Update on consensual proposals (1993 February). Role of cotrimoxazole in the primary prevention of toxoplasmosis in patients with HIV infection]. PMID- 8503611 TI - [Consensual proposals for the treatment of toxoplasmosis in patients with human immunodeficiency virus infection]. PMID- 8503613 TI - [Viral surrogate markers: their value in the therapeutic follow-up]. PMID- 8503614 TI - [Pulmonary pneumocystosis and renal transplantation: influence of the AIDS epidemic]. PMID- 8503615 TI - [Clindamycin and primaquine in the treatment of pulmonary pneumocystosis in a HIV positive female patient]. PMID- 8503616 TI - [Demodex folliculitis: a cause of pruritus in human immunodeficiency virus infection]. PMID- 8503617 TI - [Primary lymphoma of the central nervous system disclosed in the spinal cord site in a patient with human immunodeficiency virus infection]. PMID- 8503618 TI - [Cerebral embolism and aneurysm of the atrial septum]. PMID- 8503619 TI - [Immunoallergic hemolytic anemia caused by metapramine]. PMID- 8503620 TI - [Portal thrombosis, hereditary protein C deficiency and Vaquez disease]. PMID- 8503621 TI - [Adrenal insufficiency caused by bilateral hemorrhage of the adrenal glands in antiphospholipid syndrome]. PMID- 8503622 TI - [Factor XIII and hepatitis C virus infection]. PMID- 8503623 TI - [Triclonal gammopathy and cancer of the esophagus with PTH-like syndrome]. PMID- 8503624 TI - [Loffler syndrome in a female patient treated with minocycline]. PMID- 8503625 TI - [Stereotactic radiosurgery. Preliminary experience of a team of Lyon]. AB - Radiosurgery (RS) is a new technique that is being developed worldwide to treat a variety of central nervous system (CNS) diseases. We report preliminary results concerning the first 35 patients treated at our institution between October 1989 and December 1990. These patients presented with pituitary adenomas (PA: 12 patients), primary CNS tumors with different histologies (11 patients), arteriovenous malformations (AVM: 6 patients), acoustic neurinomas (3 patients) and CNS metastases (3 patients). All patients were treated with a linear accelerator and received a single dose of 20 Gy delivered on the 70% isodose curve localized stereotactically by mean of either a CT scan or angiography. Preliminary results with a median follow-up of 26 months were as follows. AVM had totally disappeared in 3 patients after 12 and 17 months, and remained stable in 3 at 6 and 26 months. In 3 PA patients, the adenoma was partially regressed on the CT scan and, in 2 patients, the visual field was moderately improved; none experienced clinical improvement due to hormonal hypersecretion. One patient with neurinoma experienced clinical improvement, but the CT scan remained unchanged in the 3 patients. Of the patients with primary or secondary tumors, 8 exhibited a reduced lesion diameter on the CT scan, but 3 died later of progressive disease. Complications were not rare. In 7 patients, delayed reactions were observed: one case of cerebral edema reversed under corticotherapy; and 6 cases of neurological impairment due to brain necrosis, reversed in only one. RS appears to be an interesting approach for the treatment of deeply located AVM and for small acoustic neurinomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503626 TI - Legal medicine. PMID- 8503627 TI - The Truro Murders in retrospect: a historical review of the identification of the victims. AB - Rated among the most bizarre crimes in Australia's criminal history, the Truro Murders, like the Albury "Pyjama Girl" case in 1934, attracted widespread national interest and depended heavily on forensic odontology for the identification of the victims, and the subsequent apprehension of an offender. The serial killings of seven young women from various suburbs of Adelaide, South Australia, was revealed after their skeletonised remains were discovered near the rural township of Truro, South Australia, and two other locations, about two years after their disappearance in 1976-77. Prompt identification of the victims permitted an early start to be made on the investigation of these crimes. Comparison with dental records provided positive identification for five of the seven victims, and dental evidence supported the identification of two victims whose dental records previously had been destroyed. Cranio-facial video superimposition was used to complement the identification of all seven. This paper reviews the main events in the context of history, with particular emphasis on the problems encountered in the identification of the victims from dental records and discusses the impact of the case on the development of forensic odontology in Australia. PMID- 8503628 TI - Drug safety monitoring: an international perspective. AB - The issue of drug safety must always be considered from the patient's perspective. Efforts in drug safety monitoring must seek to improve care and give prescribers and their patients with the best possible information to make a risk benefit judgement. The concept of a 'signal' of an adverse reaction to a drug needs to be clearly understood, and the nature of the process to determine which signals become established 'adverse reactions' is important. Good clinical and pharmaco-epidemiological studies and insight are needed for the investigation of a signal. International cooperation utilising the WHO Programme for International Drug Monitoring and other organisations helps with the discovery, evaluation and dissemination of information on drug issues, but in the end it is the alert clinician who is both likely to spot new unexpected drug problems and have the individual patient knowledge to use drugs to their maximum benefit and minimal harm. PMID- 8503629 TI - Automated solid-phase extraction of opiates from urine (I). AB - The extraction of morphine and codeine in urine by C18 bonded-phase columns was studied using a fully automated solid-phase extraction system. Extracts of urine were analysed by a high-performance liquid chromatographic method. Recovery of the opiates depends on the urine pH, and the choice of washing solvents and eluent. Studies were carried out on the optimisation of eluent volume by establishing a recovery-time profile for the elution process. Regenerated C18 bonded-phase columns could be re-used with negligible carry-over and insignificant recovery loss. An automated extraction procedure was developed for morphine and codeine in urine with absolute recoveries exceeding 80%. PMID- 8503630 TI - Containment of AIDS in Singapore--legal and policy implications. AB - Law has an important supportive role in containing the spread of AIDS. This essay hopes to show the ways in which law can help and ways in which it cannot. There is a discussion of the relevant laws of Singapore including the Infectious Diseases (Amendment) Act, 1992. Areas where possible future legislation may be considered are also pointed out. PMID- 8503631 TI - Particulate matter of smoke inhalation. AB - Smoke inhalational injury is a common event, which often complicates cutaneous burns, markedly increasing mortality, especially when it is associated with facial burning. The primary source of injury in the upper respiratory tract is heat, but thermal injury does not usually extend beyond the bifurcation of the trachea. Within the lung, it is the deposition of particles, derived from the substrate burnt, together with the toxic gases given off which causes the injury. The way in which the injuries are caused is not completely understood, but it appears to be a direct response to the stimulation of the inflammatory response. This seems to give rise to a feedback mechanism. The continued presence of particulate matter may lead to continuing damage and thus to impaired respiratory function in survivors. The nature of the particulate matter, like the toxic fumes given off, reflects the chemical nature of the substances burnt, and is not as is commonly assumed, merely carbon. PMID- 8503632 TI - Automated solid-phase extraction of opiates from urine (II). Establishing criteria for the detection of opiate abuse. AB - Automation in the laboratory was taken one step further with the introduction of automated solid-phase extraction of opiates from urine using C18 bonded-phase columns as an alternative to traditional liquid-liquid partitioning. A comparison of the automated procedure with an established liquid-liquid extraction procedure showed a linear correlation between the two over the concentration range studied. Criteria for the identification of opiate abusers were established to adapt this new methodology to large-scale screening of urine specimens. PMID- 8503633 TI - Differentiation of discolouration in a body by an erythrocyte membrane component, glycophorin A. AB - In a differential study to distinguish antemortem bruise from postmortem infiltration of haemoglobin on the skin, a component of erythrocyte membrane, glycophorin A was extracted from experimental bruise and haemoglobin infiltration lesions over set periods of time. This extraction was accomplished by utilising anti-glycophorin A serum, after which the difference between the two lesions was evaluated. The glycophorin A was recovered from the bruise lesions satisfactorily up to the ninth to twelfth days and showed good resistance to putrefaction. In contrast, no glycophorin A was detected in haemoglobin infiltration lesions taken at any time. Glycophorin A was also detectable in human vital bruises which were taken in autopsies of four hours to ten days postmortem. These results suggest that a differential diagnosis of antemortem bruise and postmortem haemoglobin infiltration is possible in advanced stages of death. PMID- 8503634 TI - A study of coroner's cases from hospitals: a comparison of autopsy and clinical diagnosis. AB - This study compares the clinical cause of death and the autopsy cause of death. The study population of 623 cases consists of all coroner's cases for the year 1990 subjected to autopsy, which were hospital cases, and which were not dead on arrival. The clinical cause of death was confirmed by autopsy in 72% of cases. For unnatural deaths (260 cases), the agreement between the clinical cause of death and autopsy diagnosis was 96%. However, in natural deaths and in deaths related to surgical or therapeutic procedures (363 cases), the agreement was much lower, being 54%. The percentage agreement was lower in some categories than others, notably respiratory conditions (51%) and circulatory conditions (42%). Agreement was particularly poor in the clinical diagnosis of myocarditis (0% agreement), pulmonary thrombo-embolism (33%), cerebro-vascular accidents (36%) and pneumonia (45%). Thus death certification in these categories would have been a particularly unreliable source of diagnostic data. PMID- 8503635 TI - Disputed paternity: the historical perspectives. AB - Requests for blood tests to resolve issues of disputed paternity fall under three main categories: (1) Proof of adultery; (2) Proof of kinship (a) in claims for citizenship, (b) to make material changes to the Birth Certificate, (c) for settlement of family disputes usually in inheritance matters; and (3) Investigation of sex crimes like rape and incest where a child is the result of the union. A broad overview is given on the venous red cell and serum blood groups used for paternity investigations. The laws of inheritance as applied to blood group investigations for disputed paternity are discussed. A survey of cases investigated on red cell and serum genetic markers since 1978 till 1990 showed an average of 5.5 cases a year with exclusion of the putative father in 19% of cases. PMID- 8503636 TI - Toxicology Services in Singapore. AB - The toxicology laboratory provides a whole range of forensic toxicology services to the doctors, pathologists, law enforcement agencies and the public. This paper, anchored in one hundred and ten years of history, traces the practice and development of this laboratory to the present day of offering services in blood for alcohol determinations, antemortem biological fluids (gastric aspirate, blood, etc.) and postmortem biological fluids and tissues (liver, kidney, etc.) for drugs and poisons screen. This paper spells out in detail the nature of specimens required, the analytical techniques used, the toxins looked for and the medico-legal implications of our analytical findings. A number of recent cases of interest are presented. PMID- 8503637 TI - Studies of felonious crimes by the University Department of Forensic Medicine in Kumamoto Prefecture, Japan. AB - This paper gives an understanding of Japan in the respect of forensic medicine. The fight against felonious crimes in Kumamoto is introduced by reference to the police system, crime statistics, an association of police surgeons and medico legal autopsy in Kumamoto Prefecture. The police have 23 local police stations with 2,670 police officers and the unique Hashutsu-sho and Chyuzai-sho systems. The crime rate is not very high, but crimes committed by Yakuza groups and traffic accidents are major problems in Kumamoto. Medico-legal autopsy is performed in the university department on only criminal and suspected cases after examination of the body externally by a police surgeon. Two illustrative cases are also introduced in this report, which shows good cooperation among the police force, the university department of forensic medicine, and police surgeons in Kumamoto, Japan. PMID- 8503638 TI - Dope testing in sports: scientific and medico-legal issues. AB - The paper reviews current issues related to dope testing in sports from the scientific as well as the medico-legal perspectives. The various types of doping, their modes of use and the dangerous consequences of misuse are discussed. It was pointed out that national doping control programmes are essential for the prevention of drug abuse in sports and that proper procedures for sampling and analysis in accredited laboratories are necessary to ensure that justice is done for the competitors and for all others concerned. There was a need for continuous vigilance against drug abuse in sports. Continuous improvement of the dope testing methods, better understanding of the pharmacology of the drugs involved and regular reviews of the banned drugs list are essential to advance the cause of dope control in sports. PMID- 8503639 TI - The role of the doctor in drug safety. AB - The safe use of drugs is the collective responsibility of the doctor, the patient and the pharmaceutical industry. The risk of adverse drug reactions though not totally preventable, can be minimised. The doctor can help to decrease the frequency and severity of adverse drug reactions by observing the basic principles of "good prescribing", namely: (i) the benefits of drug therapy should outweigh the risks of adverse drug reactions; (ii) individualization of drug therapy; and (iii) monitoring efficacy and adverse reactions. PMID- 8503640 TI - Sudden death due to incarcerated Bochdalek hernia in an adult. AB - Bochdalek hernias presenting in adulthood are rare occurrences. They present commonly as acute surgical emergencies. A case of sudden death due to perforation of gastric ulcer in an incarcerated Bochdalek hernia is reported. This has not been previously documented. Recent literature on the subject is also reviewed. PMID- 8503642 TI - Monitoring of adverse drug reactions in the pharmaceutical industry--the scene in the United Kingdom. AB - In the United Kingdom, all suspected reactions to newly marketed drugs and serious, suspected reactions to established drugs are reported by doctors, dentists, coroners and pharmaceutical companies to the Medicines Control Agency. The information is entered onto the Agency database and analysed before being made available in regular reports. Post-marketing surveillance of newly licensed drugs is carried out in a number of ways: protocolled studies involving up to 10,000 patients, prescription tracing, and databases using input from general practitioners or hospitals. European Community pharmacovigilance requirements were due to become effective in 1992, or soon after. These may involve companies in a review of the structures of their reporting department and, without care on the part of the Community, could result in duplication of reporting. Risk/benefit analysis of drug use is led by the International Foundation based in Geneva. The aim is to improve the management of drug safety, both within the industry and the medical profession. In the UK, a risk assessment group has grown up which includes, among others, all interested UK companies and representation from the Medicines Control Agency. PMID- 8503641 TI - No-fault compensation and performance review. AB - Two major issues in relation to medical malpractice are discussed. The first is "no-fault compensation", an alternative to the present tort system long established in most countries, including Singapore, where negligence must be proved before a claim can succeed. The second is "performance review", a new concept for monitoring and correcting under-performing medical practitioners against whom a complaint has been laid. Both these issues are currently under active discussion and are arousing political notice and professional controversy. Though the article describes the British situation, there is much of contemporary relevance for Singapore, which has such a similar system of medical practice. PMID- 8503643 TI - Human immunodeficiency virus infection confronts the law, ethics and society. AB - The full panorama of the AIDS problem is filled with contradictions. There are those who consider the AIDS sufferers--primarily gays and intravenous drug abusers--as "the bad group". Yet, there are also innocent victims: recipients of blood and blood products and the unknowing sex partners. Regardless of the circumstances under which they contracted the disease, many AIDS sufferers are hated because they are perceived as menaces. Such feelings are triggered by raw emotions, hysteria, anxiety, insecurity, fear, even phobias and paranoia in those who do not have, and who often do not understand the disease. This frequently results in discrimination and bias that may be aggravated by scientific and societal ignorance. Education of those who do and do not have AIDS is hampered by underlying economic problems: poverty, indigence and low social status, as well as taboos regarding discussion of sex and contraception. No disease in this country has created a greater dilemma among the public or the professions concerned with and involved in its care and management, as AIDS. A study of the magnitude of the problem and its impact reveals that it is beset by a "damned if you do, and damned if you don't" result, with the bottom line ultimately involving the benefit versus risk rule. An overview of the AIDS problem reveals particular areas of medical, societal, legal and ethical-moral concern that frequently overlap. PMID- 8503645 TI - Adverse drug reactions--tales of a forensic pathologist. AB - Drugs can produce adverse reactions in susceptible patients. This can range from minor discomfort to major morbidity or even death. The pharmacological properties of certain drugs have a high potential in producing these adverse reactions, especially if large doses are given or given simultaneously with interacting drugs or given in the presence of renal or liver dysfunction of the patient. Clinicians should be aware of the potential toxicity of the drugs they prescribe and their interacting drugs. In Singapore, deaths due to adverse drug reaction are regarded as unnatural deaths and they should be reported to the Coroner. These cases are usually subjected to a post-mortem examination. Clinicians are not allowed to sign up cases of death due to adverse drug reactions and those who do so will be subjected to queries from the Registrar of Death and the Coroner. Every year doctors have been called up to explain their misdeeds and warned. Fortunately there are not many such cases. Some cases of deaths due to adverse reactions to tetracyclines, sulphur, phenylbutazone, penicillin, paracetamol, etc will be discussed. PMID- 8503646 TI - Prevention of adverse drug reactions: role of the patient (consumer). AB - The prevention of adverse drug reactions should be a collective responsibility of the pharmaceutical industry (the drug manufacturer), the doctor (the prescriber of drugs) and the patient (the consumer of drugs). Patients themselves can play a significant role in the prevention of adverse drug reactions, in particular, ensuring a high level of compliance with medication instructions can maximise therapeutic effects and avoid or minimise the possible occurrence of potentially adverse reactions. Inadequate compliance can lead to toxicity or treatment failure (clearly exemplified in anticonvulsant, anticoagulant and immunosuppressive therapy) and, consequently, to increased treatment costs and a possible fatal outcome for the patient. Patients should also reject the belief that there is a "pill for every ill" and avoid indiscriminate self-medication and doctor hopping. Some DOs and DON'Ts for patients are also included as guidelines to prevent or minimise the occurrence of adverse drug reactions. PMID- 8503644 TI - Parentage determination on placental tissues through deoxyribonucleic acid fingerprints. AB - Investigation of genomic polymorphisms detected by a mini-satellite "Myo" probe gives distinct and different Deoxyribonucleic Acid (DNA) fingerprints of chorionic villus and decidual membrane in the same placenta. The chorionic villus, which is regarded as the extra-embryonal tissue, represents the essential embryonal DNA fingerprint pattern, while the decidual membrane reveals the maternal pattern. A comparison between the DNA fingerprints from the chorionic villus and from the blood sample of the suspected father provides the possibility of setting a paternity test in the early gestational stage. Twenty-eight cases of paternity test on aborted placental tissues by DNA fingerprints were analysed. PMID- 8503647 TI - The legal threat to medicine reconsidered. AB - The paper is concerned, in the main, with selective non-treatment of those incapable of making treatment decisions of their own. It draws attention to the conflict between the law and the medical profession in this field which was predicted some ten years ago and traces the British case law from then until the present day. It concludes that there is no such legal threat to medical practice in Great Britain and that any doubtful practices are currently controlled through the concept of the health care team. PMID- 8503648 TI - Adverse effects of pharmaceutical excipients in drug therapy. AB - Everyone who prescribes a modern formulated drug is aware of the risks of adverse reactions due to the properties inherent in the active ingredients, but not all are aware of the latent risks due to the excipients. The latter risks are compounded when inappropriate and inferior quality excipients are used. When investigating reports of adverse drug reactions, the possibilities of excipient contributed reactions must not be overlooked, though such possibilities may appear to be remote. Tragic accidents attributable to excipients have occurred and are on record. Preventive measures include frequent inspection and laboratory examination of imported and locally manufactured formulated drugs to monitor the safety of their excipients and the quality of the raw materials used in their manufacture. PMID- 8503649 TI - [Importance of mutations interfering with mouse development]. AB - In the mouse several point mutations and a great variety of chromosomal rearrangements are available. They all represent useful tools for experimental studies in developmental biology. This review provides, with the help of a few examples, an overview of the importance of the mouse for studies of the genetics of mammalian development. PMID- 8503650 TI - [Determination of the dorso-ventral polarity of the Drosophila embryo]. AB - Embryonic pattern formation has been studied extensively in many organisms. In Drosophila, the powerful combination of genetics cytoplasm transplantation experiments, as well as recent molecular data, have helped to elucidate the mechanisms responsible for the establishment of embryonic polarity. A small number of genes, most of them maternally expressed, are involved in this process and participate in four independent systems--three for the antero-posterior axis (A/P) and one for dorsoventral axis (D/V)--which define various embryonic territories by specifically localized cues. This review concerns the definition of the dorsoventral polarity responsible for the establishment of the germ layers of the embryo. Dorsoventral development is regulated by a single group of maternally expressed genes: the "dorsal group" of genes. It includes 11 genes, the loss of function of any of which results in a dorsalized development, whereas mutation of the 12th gene, cactus, results in a ventralized development. These genes are arranged according to a functional hierarchy, and have been shown to cooperate in the formation of a graded nuclear concentration of the dorsal gene product. The dorsal product corresponds to the dorsoventral morphogen and is homologous to the transcription factor NF-kappa B. Among the 11 genes of the dorsal group, 3 are required in the somatic line. This suggests the existence of inductive signals originating during oogenesis from the follicle cells that surround the developing oocyte. This somatically expressed spatial information probably controls dorsoventral development by defining the polarity of a signal transducing pathway that specifically activates the nuclear uptake of the dorsal product. This model, highlights the importance of the polarity of the egg chamber, and suggests that it is the oocyte nucleus due to its asymmetrical localization, that determines the dorsoventral pattern formation of the embryo. PMID- 8503651 TI - The genetics of skeletal development. AB - A genetic analysis of biologic processes has provided substantial advances in developmental biology. Whereas the genetic analysis of Drosophila is a potent system, recently developed tools have enabled a genetic analysis of the development of vertebrates. For these studies, numerous mouse mutants are available and many more will be introduced in the near future. Mutations involving the skeleton are easy to detect. This article reports the phenotype and molecular analysis of two mutant mouse strains with skeletal abnormalities, undulated (un) and Danforth's short tail (Sd). The role of the corresponding genes in skeletal development of these two mutants and the basis for their genetic interaction are discussed. PMID- 8503652 TI - [Parental genome imprinting]. AB - Genetical as well as experimental embryology methods have permitted, in recent years, to uncover a very important feature of mammalian embryonic development: it has been shown that female and male genomic complements are differentially imprinted in such a way that contribution of both a maternally and a paternally derived genome are absolutely necessary for the embryo to complete its normal development. Differential genomic imprinting seems therefore to impose some new and essential kind of information to the one already contained in the genomic sequences. The differential imprinting should be imposed on the genetic material during gametogenesis and persist throughout somatic development after fertilization. It should then be erased in the germ cell line and be established again in sperm and egg genomes. The recent discovery of several mouse genes which are imprinted should permit to address the question of the molecular mechanisms of imprinting. PMID- 8503653 TI - [An exceptional combined malformation: duplication of the lower urinary tract, the vulva and the posterior intestine]. AB - The authors report the case of a 6 year old girl with bladder duplication, urethral duplication, genital system duplication associated with colonic duplication and low double anorectal anomalies. This patient presented two hemivertebrae at T9 and T11. This girl died a few days after admission from internal obstruction and septicemia. The embryological features especially the possibility of associating two different embryopathogenic mechanisms in the pathogenesis of this combined malformation (Split notochord syndrome and fissure of the urogenital system), and diagnostic and therapeutic aspects are studied in relation to this case and a review of the literature. PMID- 8503654 TI - [The urinary tract in pregnancy]. AB - Pregnancy is associated with morphologic alterations of the urinary tract, of which physiological ureterohydronephrosis is the most common. Acute pyelonephritis and obstruction by stones are the two most frequent urinary tract diseases of pregnancy. Medical imaging aims at differentiating physiological ureterohydronephrosis from obstruction and at detecting infections. Ultrasonography plays a central role. Limited roentgenographic investigations can be performed during the second and third trimester. Magnetic resonance imaging can be expected to gain more widespread use in the near future. PMID- 8503655 TI - [Cystine lithiasis and its treatment with d-penicillamine. The experience in a nephrology service in a 23-year period. Apropos of 26 patients]. AB - From 1968 through 1990, 26 patients with cystine lithiasis were followed-up for a mean of 10.6 +/- 6.7 years in the department of Nephrology of the Pellegrin Hospital in Bordeaux, France. Clinical and surgical features in these patients are reported as well as the experience acquired with the use of D-penicillamine over the 23-year study period. Long-term D-penicillamine treatment can be used in patients with cystinuria and is both effective and safe. Use of other thiol compounds for preventing cystine stone formation was not necessary in our patients. PMID- 8503656 TI - [Experimental application of the jet scalpel in renal surgery in the dog]. AB - With the aid of an original jet cutting apparatus 29 partial and 3 hemiresections of the kidney were performed in dogs. Another 10 animals, as a control group, were subjected to ordinary scalpel resection and electric knife treatment. Consideration has been given to immediate and early postoperative blood losses as well as to immediate and later-stage histomorphological changes in the resected organs. Due to the fine presentation of blood vessels and the kidney's pyelocaliceal system by the cutting jet, intraoperative blood loss was reduced. Other advantages of the system include reducing overall duration of the surgical intervention, no need for special training of the operator to use the apparatus, low cost of the apparatus and environmental cleanliness in the operation room compared with the use of conventional devices used for parenchymal resection. PMID- 8503657 TI - [Has interleukin 2 modified the outcome of metastatic kidney cancer?]. AB - Immunotherapy offers a limited but definite hope in the course of metastatic renal cancer. Interferon alpha gives 2% complete remissions and 14% partial responses. Interleukin 2 achieves 5-10% complete remissions and 20% partial responses. The combination of the two agents does not really improve the results. In contrast, culture of TIL cells in the presence of IL-2 provides encouraging results. PMID- 8503658 TI - [Urinary tract tumor in a horseshoe kidney diagnosed after renal trauma]. AB - The discovery of a urinary tract tumor in a horseshoe kidney following renal trauma led the authors to report this case. They emphasise the fact that this association is very rare, the importance of follow-up urography in cases of renal trauma, and that the persistence of urographic abnormalities justifies the use of computed tomography. They also indicate the technical details of horseshoe kidney surgery. PMID- 8503659 TI - [Pseudotumoral lipomatosis of the renal sinus]. AB - Two cases of pseudotumoral lipomatosis in the renal sinus and responsible for clinical symptoms and radiological renal alterations are reported. Emphasis is put on the misleading features of this disease which may suggest a malignancy. Outcome is consistently favorable. Computed tomography ensures the preoperative diagnosis, avoiding an unnecessary nephrectomy. PMID- 8503660 TI - [Retrovesical hydatid cyst. Apropos of 2 cases]. AB - A hypogastric mass compressing the bladder in an adult, in a zone endemic for hydatid disease, should raise to suspicion of a retrovesical cyst, especially as the cyst sometimes opens into the bladder resulting in haematuria and hydatiduria. Intravenous urography and ultrasonography facilitate the topographical diagnosis. Treatment is surgical: transperitoneal cystectomy and pericystic resection as extensive as possible with exploration of the abdomen looking for other sites (liver, mesentery, omentum). This treatment was successful in the two cases reported here. In conclusion, a stable cure can be obtained by adopting a well defined therapeutic approach to these rare lesions. PMID- 8503662 TI - Haemophilus influenzae type b. PMID- 8503661 TI - Gene therapy for cystic fibrosis. PMID- 8503663 TI - How to get drugs into the respiratory tract. PMID- 8503664 TI - False allegations of abuse and Munchausen syndrome by proxy. AB - Fourteen children from seven families are reported for whom false allegations of abuse were made by the mother. Twelve children were alleged to have incurred sexual abuse, one both sexual and physical abuse, and one physical abuse alone. Thirteen of the children had incurred, or were currently victims of, factitious illness abuse invented by the mother. The one child with no history of factitious illness abuse had a sibling who had incurred definite factitious illness abuse. The false allegations of abuse did not occur in the context of parental separation, divorce, or custody disputes concerning the children. They occurred in the context of Munchausen syndrome by proxy abuse. The age of the children, 3 to 9 years, was older than the usual age for Munchausen syndrome by proxy abuse. The mother was the source of the false allegations and was the person who encouraged or taught six of the children to substantiate allegations of sexual abuse. PMID- 8503665 TI - Non-accidental salt poisoning. AB - The clinical features of 12 children who incurred non-accidental salt poisoning are reported. The children usually presented to hospital in the first six months of life with unexplained hypernatraemia and associated illness. Most of the children suffered repetitive poisoning before detection. The perpetrator was believed to the mother for 10 children, the father for one, and either parent for one. Four children had serum sodium concentrations above 200 mmol/l. Seven children had incurred other fabricated illness, drug ingestion, physical abuse, or failure to thrive/neglect. Two children died; the other 10 remained healthy in alternative care. Features are described that should lead to earlier detection of salt poisoning; the importance of checking urine sodium excretion, whenever hypernatraemia occurs, is stressed. PMID- 8503666 TI - Growth and growth hormone secretion after bone marrow transplantation. AB - This study analyses the growth and the growth hormone secretion of children given various conditioning protocols before bone marrow transplantation (BMT). Twenty nine children (14 boys, 15 girls) given BMT were classified according to their conditioning protocol: total body irradiation (TBI) given as a single exposure of 10 Grays (Gy, group I, 11 cases), or 8 Gy (group II, four cases), 12 Gy given as six fractionated doses (Group III, seven cases), or chemotherapy alone (group IV, seven cases). The arginine-insulin stimulated growth hormone peak, 2-7.5 years after BMT, was > 10 micrograms/l in all patients except four from group I (6.9 8.9 micrograms/l). A second growth hormone secretion evaluation was performed in 10 group I patients because of persistent low growth velocity despite a normal growth hormone peak. There were no significant changes in the mean (SEM) stimulated growth hormone peak (18.4 (2.2) v 20.1 (3.6) micrograms/l) at 3 (0.3) to 5.2 (0.6) years after BMT. The sleep growth hormone peaks and concentrations (n = 6) were normal. The mean cumulative height changes (SD) during the three years after BMT were: -1.4 (0.2) in group I, -0.1 (0.4) in group II, -0.4 (0.2) in group III, and 1.5 (0.5) in group IV; this was significant in groups I and IV. The final heights of two monozygotic twins (BMT donor and recipient) had differed by 17.5 cm, despite them both having normal growth hormone peaks and puberty. Eight patients, treated for congenital immune deficiency syndrome, were growth retarded at the time of BMT. Of these, only those conditioned by chemotherapy alone had significant catch up growth (2(0.6)SD) while those conditioned by a single Gy exposure did not (0(0.4)SD). It is concluded that the total radiation dose is critical for growth evolution, as is the fractionation schedule. For the TBI doses and the interval since BMT studied, there was no correlation between growth hormone peak and the height loss. The rapidity of decreased growth velocity after TBI and the comparison between the monozygotic twins suggest that radiation induced skeletal lesions are partly responsible for the decreased growth. PMID- 8503667 TI - Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history. AB - The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease. PMID- 8503668 TI - Treatment of acute bronchiolitis with Chinese herbs. AB - In a randomised single blind trial the Chinese herbs Shuang Huang Lian were evaluated for the treatment of acute bronchiolitis. Children with acute bronchiolitis and serological evidence of recent respiratory syncytial virus infection were studied in a tertiary hospital in Harbin, China. The 96 children were randomised into three treatment groups: herbs, herbs with antibiotics, and antibiotics alone. The herbs were prepared by the medical school pharmacy and administered daily by intravenous infusion for seven days. The main outcomes, assessed blindly, were symptomatic improvement in cough, fever, wheezing, chest signs, and duration of stay in hospital. The mean duration of symptoms from the start of treatment was 6.2 (confidence interval 5.6 to 6.9) days in the two groups treated with herbs compared with 8.6 (confidence interval 7.5 to 9.8) days in the group treated with antibiotics alone. The mean reductions in duration of clinical manifestations for treatment with antibiotics alone compared with herbs were: from 3.1 to 1.5 days for fever, 9.1 to 6.1 days for cough, 6.5 to 4.1 days for wheezing, and 7.2 to 4.9 days for chest crackles. No adverse effect of Shuang Huang Lian herbal treatment was detected. In conclusion, this study confirms Chinese experience with Shuang Huang Lian that it is safe and effective, and warrants further study. PMID- 8503669 TI - Nasal IgA response in wheezy infants. AB - It is unknown why some infants wheeze during upper respiratory tract infections. One possibility is that secretory IgA, which has a major role in mucosal defence against viral infection, might be deficient in wheezy infants. The nasal IgA response to upper respiratory tract infection in 32 wheezy infants (median age 5.8 months) was compared with nine siblings (median age 2.6 years) who had nasal symptoms only. Nasal lavage was performed during infections and on follow up when free from symptoms, using inulin as a marker of dilution to determine absolute concentrations of IgA in the nasal secretions. The two groups showed a similar increase in total IgA and total protein levels during infection, but secretory IgA concentrations were unchanged. This study shows that wheezy infants have a normal nasal IgA response to infection and that the increase in total IgA during early infection is due to plasma exudation rather than increased production of secretory IgA. PMID- 8503670 TI - An assessment of a new breath actuated inhaler device in acutely wheezy children. AB - A randomised double blind, two period cross over study was designed to compare the ability of 51 hospitalised asthmatics with acute exacerbations to use each of two inhalers. The inhalers compared were a new breath actuated metered dose inhaler, the Autohaler inhalation device, and a dry powder device, the Rotahaler. Preassessment data included the measurement of peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), pulse rate, and oxygen saturation. Therapeutic response to each inhaler was compared by measurement of PEFR, oxygen saturation, and pulse rate. PIFR was sufficient in all children to fire the Autohaler, including the youngest. No significant difference was found between the two inhalers as assessed by PEFR. However the Autohaler inhalation device could be actuated 99/100 times successfully compared with 74 for the Rotahaler. There was a consistent, but clinically insignificant, increase in pulse rate after use of the Rotahaler compared with the Autohaler. All 11 patients under 6 years of age failed to empty the Rotahaler but five of these patients received a significant benefit from using the Autohaler compared with after the Rotahaler. A significant drop in oxygen saturation was observed 15 minutes after use of either inhaler. This may at times reach levels of clinical importance. PMID- 8503671 TI - Sleep characteristics of asthmatics in the first four years of life: a comparative study. AB - The association between asthma and sleep disturbances was assessed as part of a community survey of sleep patterns in children aged 4-48 months. A questionnaire covering the area of past and present sleep and settling behaviour, as well as health history and demographic data, was administered to 752 mothers of children visiting 14 well baby clinics. Fifty one (6.8%) of the children who were diagnosed as having asthma by their paediatricians were compared with the remaining healthy controls (children with perinatal problems, other chronic illnesses, developmental problems, or repeat admissions to hospital were excluded). Thirty nine per cent of the children with asthma and 38% of the normal controls were identified as regular wakers. The number of interrupted nights each week, settling time, and sleep duration were comparable. In the children with asthma an uninterrupted night's sleep was acquired later than in the control group. Parental perception of the severity of the sleep problem was similar in the two groups, as were the calming techniques. It is concluded that this study does not support a significantly increased prevalence of sleep disturbances among young children with asthma compared with their healthy peers. PMID- 8503672 TI - Measurement of gastric emptying in infants with pyloric stenosis using applied potential tomography. AB - Gastric emptying in a group of 49 vomiting infants with infantile hypertrophic pyloric stenosis (IHPS) was investigated using applied potential tomography. Fourteen asymptomatic infants were also studied as a control group. A Dioralyte test feed (25 ml/kg/feed) was used for all the studies. The infants with IHPS were investigated before and at two, four, and seven days after an operation; the other infants were investigated once. The results show that the infants with IHPS have no or little gastric emptying before the operation and gradually return to normal emptying by the seventh day after the operation. A significant difference in gastric emptying was noted between the control infants and the infants with IHPS before and at two and four days after the operation. The applied potential tomography method is suitable for studying gastric emptying in infants, with no morbidity nor complications. It also allows multiple studies to be performed without upset or discomfort. PMID- 8503673 TI - Audit of paediatric cardiopulmonary resuscitation. AB - The causes and outcome of cardiopulmonary arrests were studied in a paediatric hospital over a 12 month period. Forty five resuscitation attempts were made involving 41 children and one adult. Twenty eight (68%) of the children were under 1 year of age and 10 (24%) were neonates. Twenty one (47%) arrests were primarily respiratory and 11 (24%) primarily cardiac in origin. Eighty two per cent of the respiratory arrests had an initially successful outcome, compared with 36% of the cardiac arrests. Overall 70% of cardiopulmonary resuscitation attempts were initially successful. There were no survivors from resuscitation attempts longer than 30 minutes. At 12 months after cardiopulmonary resuscitation 15 (37%) of the children were still alive. The 11 children who had been neurologically normal before the arrest showed no evidence of neurological damage after successful cardiopulmonary resuscitation. PMID- 8503675 TI - Consultant paediatric outreach clinics--a practical step in integration. AB - Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest. PMID- 8503674 TI - The effect of temperature reduction on respiratory rate in febrile illnesses. AB - A raised respiratory rate is a useful sign in the diagnosis of pneumonia in children. It was observed that children with malaria and other febrile illnesses may also present with a raised respiratory rate. To determine the extent to which increased body temperature contributes to the raised respiratory rate observed in these children the effect of change in body temperature on respiratory rate was measured in 186 sick Gambian children with a raised respiratory rate, including those with pneumonia or malaria. A temperature dependent effect on respiratory rate of 3.7 breaths per minute per degree centigrade was demonstrated for the whole study cohort, with no significant difference between children with pneumonia or malaria. Twenty three per cent of children with pneumonia whose temperature fell had a final respiratory rate below that currently recommended by the World Health Organisation for the diagnosis of pneumonia. It is concluded that respiratory rate is to some extent dependent on body temperature in children with febrile illnesses such as pneumonia and malaria, but that this does not alone account for the raised respiratory rate seen in these children. The effect of reduction in body temperature on respiratory rate does not help to distinguish children with pneumonia from those with malaria. A history of recent use of an antipyretic or other measures to control fever is important when evaluating children for possible pneumonia. PMID- 8503676 TI - Dummies and the sudden infant death syndrome. AB - The association between dummy use and sudden infant death syndrome (SIDS) was investigated in 485 deaths due to SIDS in the postneonatal age group and compared with 1800 control infants. Parental interviews were completed in 87% of subjects. The prevalence of dummy use in New Zealand is low and varies within New Zealand. Dummy use in the two week period before death was less in cases of SIDS than in the last two weeks for controls (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.57 to 1.02). Use of a dummy in the last sleep for cases of SIDS or in the nominated sleep for controls was significantly less in cases than controls (OR 0.44, 95% CI 0.26 to 0.73). The OR changed very little after controlling for a wide range of potential confounders. It is concluded that dummy use may protect against SIDS, but this observation needs to be repeated before dummies can be recommended for this purpose. If dummy sucking is protective then it is one of several factors that may explain the higher mortality from SIDS in New Zealand than in other countries, and may also explain in part the regional variation within New Zealand. PMID- 8503677 TI - Respiratory function in the prune-belly syndrome. AB - Respiratory function was evaluated in 11 patients with prune-belly syndrome. Nine had evidence of gas trapping and six of restrictive lung disease. These abnormalities of lung function appear to be secondary to the musculoskeletal disorder associated with prune-belly syndrome rather than parenchymal lung disease. PMID- 8503678 TI - Dizygotic twins discordant for HIV and hepatitis C virus. AB - Twin girls were born at 37 weeks' gestation to a mother infected by HIV and hepatitis C virus. Twin 1 had symptomatic HIV infection by 9 months but was negative for hepatitis C virus antibody and RNA. Twin 2 became HIV antibody negative by 15 months but was positive for antihepatitis C virus and RNA. PMID- 8503679 TI - Growth in CHARGE association. AB - Growth data is shown from 44 children (aged 0.5-18 years; 27 boys, 17 girls) with CHARGE association. Children had a normal birth weight and length, but in infancy there was a fall in centiles. Children remained small and there was pubertal delay in boys. Close monitoring of growth with early detection and intervention is recommended. PMID- 8503680 TI - The assessment of vision in the preschool child. PMID- 8503681 TI - Contracting for child health services in the community. PMID- 8503682 TI - Audit of screening for congenital hypothyroidism. PMID- 8503683 TI - Patient knowledge and compliance with growth hormone treatment. PMID- 8503684 TI - Continuous infusion of zidovudine in HIV related thrombocytopenia. PMID- 8503685 TI - Haemorrhagic shock encephalopathy or near miss sudden infant death syndrome? PMID- 8503686 TI - Reporting of vaccine associated mumps meningitis. PMID- 8503687 TI - Treatment of refractory ulcerative oesophagitis with omeprazole. PMID- 8503688 TI - Recurrent parotitis. PMID- 8503689 TI - Kawasaki disease. PMID- 8503690 TI - Is filaggrin really a filament-aggregating protein in vivo? AB - Filaggrin, a basic protein of the stratum corneum, was named as such because of its capability to aggregate keratin intermediate filaments in vitro. To investigate its filament-aggregating capability in vivo, we performed immunoelectron microscopy in three autosomal dominant genodermatoses serving as in vivo models of abnormalities of keratin filament aggregation. In bullous congenital ichthyosiform erythroderma Brocq and epidermolytic palmoplantar keratoderma Voerner suprabasal clumping of keratin filaments prevents the normal spreading of keratohyalin between keratin filaments. Keratohyalin granules, either isolated or attached to clumped keratins, were specifically labelled by the anti-filaggrin antibody, whereas tonofilament clumps did not show any reaction. In epidermolysis bullosa herpetiformis Dowling-Meara the abnormal filament aggregation occurred in basal cell keratins where no reaction of the anti-filaggrin antibody was detected. In high level keratinocytes with normal distribution of tonofilaments, normal stellate keratohyalin reacted specifically. In all instances keratin filament clumping occurred independently of, and spatially separated from, the first signs of profilaggrin synthesis and keratohyalin granule formation. Thus, in these disorders, filaggrin is not involved in filament aggregation. PMID- 8503691 TI - Abnormalities of connective tissue components in lesional and non-lesional tissue of patients with pseudoxanthoma elasticum. AB - Pseudoxanthoma elasticum (PXE) is a disorder of connective tissue in which abnormalities of elastic tissue and collagen are found. The purpose of this study was to examine the ultrastructure and distribution of connective tissue components in lesional and non-lesional skin of patients by means of indirect immunofluorescence, electron microscopy and indirect immunoelectron microscopy. Prominent abnormalities of elastic tissue were seen on electron microscopy and confirmed by immunoelectron microscopy. Abnormal elastic fibers containing electron-dense bodies and holes were seen even in non-lesional skin. In addition, the normal pattern of collagen bundles was disrupted in lesional skin, but not in non-lesional skin of patients with PXE. The majority of individual collagen fibrils appeared normal by electron microscopy. The distribution of type IV collagen and laminin was normal in small blood vessels. Finally, abnormalities in the distribution of fibronectin were seen. The finding of atypical elastic fibers in non-lesional skin supports an early role for elastic tissue components in the pathogenesis of PXE. Interactions between elastin, collagen and other matrix substances may explain some of the abnormalities seen. PMID- 8503692 TI - A majority of proliferating T cells in cutaneous malignant T cell lymphomas may lack the high affinity IL-2 receptor (CD25). AB - IL-2 is a major growth factor for all T-cell subsets acting via a specific membrane receptor. To investigate its role in the pathogenesis of cutaneous T cell lymphomas (CTCLs), we analysed the expression of high-affinity IL-2 receptors (IL-2Rs) on proliferating cells in these disorders. We showed by immunohistochemical double staining that most cycling cells do not express high affinity IL-2Rs. Four T-cell lines were established from patients with CTCLs. Two lines required both IL-2 and IL-4 for growth, one line required IL-2 and one line IL-4 alone. The last of these lacked expression of the IL-2R alpha-chain. Thus, IL-2 may not be the only, or the most important, growth stimulus in CTCLs and reactive skin infiltrates. T helper cells, which dominated the infiltrate, might represent TH2 cells. PMID- 8503693 TI - Surprisingly high levels of anaphylatoxin C5a des Arg are extractable from psoriatic scales. AB - Water-soluble extracts from psoriatic scales and normal human skin were prepared using either phosphate-buffered saline, pH 7.2, or 0.1 M carbonate buffer, pH 10.8. Anaphylatoxin C5a des Arg was quantified using a novel sandwich enzyme linked immunosorbent assay (ELISA) using neoepitope-specific monoclonal antibodies. Alkali was about five to eight times more efficient than PBS in extracting C5a des Arg from scales, probably via dissociation of bound C5a des Arg. C5a des Arg concentration in scales from three patients suffering from psoriasis vulgaris varied between 2.5 and 4.6 ng/mg scale. No C5a des Arg was detectable in normal skin extracts. The biological activity of alkali-extractable C5a des Arg, i.e. chemotaxis, was preserved. The concentration of C5a des Arg relative to the concentration of albumin was taken as a parameter of the degree of complement activation in the psoriatic lesions, and was found to be more than six times higher than values attained in serum after maximum complement activation by zymosan. We conclude that complement activation may play a quantitatively important role in the inflammatory process in psoriasis. PMID- 8503694 TI - Unsuccessful attempt to detect genetic mutation in tuberous sclerosis utilizing the polymerase chain reaction. AB - Although tuberous sclerosis is supposed to be a phacomatosis inherited as an autosomal dominant trait, many cases develop without any affected parents or grandparents. In recent years, many vigorous investigations have been concentrated on finding the mutant gene, and possible candidate genes have been mapped on 9q34 and other chromosomes. In order to find a way of diagnosing asymptomatic carriers or patients, we tried to detect restriction fragment length polymorphisms (RFLPs) using the technique of polymerase chain reaction (PCR). We used a probe, MCOA12, which is located on 9q34 and has been known to show RFLPs in Caucasian tuberous sclerosis patients. However, we could not find a correlation between the phenotype and RFLP pattern in seven of eight families. PMID- 8503696 TI - Morphological analysis of in vitro human hair growth. AB - The histological and ultrastructural aspect of normal human hair follicles maintained ex vivo for 12 days was evaluated. Anagen hair follicles, dissected free of contaminating connective tissue, were maintained for up to 12 days in a serum-free medium. Macroscopic observations revealed continued viability for 12 days, at which time some follicles involuted in a manner morphologically similar to catagen. Increased growth of maintained follicles was measured from the abrupt ending of the connective tissue sheath (CTS), as no increase in this component was observed from initiation of culture. In general follicles maintained up to 8 days exhibited little divergence from normal in vivo morphologies including the persistence of functional hair bulb melanocytes--a marker of anagen. After this time melanin granules were present in dermal papilla cells, as occurs during impending involution in vivo. Heterotypic cell contact occurred in the middle to upper follicle between outer root sheath (ORS) keratinocytes and disorganized CTS. Herniation of some ORS cells away from the follicle and the occurrence of loose desmosomal junctions between ORS keratinocytes reflected loss of normal follicular cell interactions in upper follicles maintained after 8 days. Continued follicle growth correlated with the presence of mitotic matrix keratinocytes even at 12 days. After 12 days in culture most follicles involuted displaying apoptotic-like keratinocytes and hair bulb melanocytes and the presence of highly keratinized hair 'club' structures. While most follicles exhibited this orderly sequence of events, a few follicles involuted after 24 h with synchronous degeneration of all cells. Two follicles exhibited upregulated cortical cell differentiation at the level of the dermal papilla (DP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503695 TI - Partition of sodium dodecyl sulfate into stratum corneum lipid liposomes. AB - Synthetic detergents produce deleterious effects on human skin as the result of being taken up by the stratum corneum (SC). The present study aimed to determine to what extent a typical detergent enters the SC lipid lamellae, and what effect this might have on the physical properties of the lipids. These effects were studied in large unilamellar liposomes prepared from SC lipids (50% by weight of epidermal ceramides, 28% cholesterol, 17% free fatty acids, and 5% cholesteryl sulfate) by extrusion through successive polycarbonate filters of decreasing pore size, finally 400 nm. Freeze-fracture electron microscopy and light-scattering particle size analysis indicated a uniform liposome diameter averaging 230 nm. Partitioning of sodium dodecyl sulfate (SDS) into the lipid phase from aqueous buffer solutions was measured using the SC lipid liposomes and [U-14C]SDS. The partition coefficient was 416, 450, and 588 at pH 8.5 and 524, 507, and 807 at pH 7 for three different concentrations (0.1%, 0.02%, and 0.004%) of SDS. This high degree of partitioning into the liposomes is consistent with the high level of SDS partitioning seen in full SC. At the maximum, the SDS represented 18% of the liposomal lipids. Preparation of stable liposomes from SC lipids to which 10% or 20% of SDS had been added confirmed the ability of the liposomes to survive these high concentrations of surfactant. The permeability of the liposomes was enhanced as a result of SDS partitioning into the bilayers, as measured by the increased release of trapped [U-14C]glucose from these vesicles, and by their increased permeability to water in osmotic shock experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503697 TI - Immunoblot assay to study the pemphigus vulgaris antigen in normal human epidermis and COLO-16 cell line. PMID- 8503698 TI - Detection of mycobacterial DNA in paraffin-embedded specimens of lupus vulgaris by polymerase-chain reaction. PMID- 8503699 TI - Borrelia burgdorferi isolates from erythema migrans. PMID- 8503700 TI - Scanning electron microscopic study with the aldehyde-osmium-DMSO-osmium method. PMID- 8503701 TI - Presence of the autoantibody in healthy relatives of Italian patients with pemphigus vulgaris. PMID- 8503702 TI - Uterine incision and maternal blood loss in preterm caesarean section. AB - The purpose of this study was to compare maternal blood loss, as reflected by the perioperative changes in haemoglobin (Hgb), the incidence of severe bleeding (estimated blood loss > 1000 ml) at operation, and the need for blood transfusion, between patients who had classical caesarean section (CCS) and lower segment caesarean section (LSCS) at 34 weeks gestation or less. The data from 31 women delivered by CSS between 25 and 34 weeks gestation were compared, in a retrospective case-control fashion, to another 31 women delivered by LSCS. Patients were matched for gestational age at delivery, the type of anaesthesia, and the prior use of tocolytic therapy. Excluded from the study were patients who had an antepartum haemorrhage or placenta praevia. There was a significantly greater reduction in maternal Hgb and an higher incidence of severe bleeding in the CSS group compared to the LSCS group (P < 0.05). The results of this study suggest that for preterm caesarean sections, the classical incision is associated with increased blood loss compared to the lower segment incision. PMID- 8503703 TI - Oxytocin, PGE2 and PGF2 alpha stimulate the production of inositol phosphates in the rabbit myometrium. AB - Phosphoinositide breakdown is thought to be important in regulating a variety of transmembrane signal transduction in the action of oxytocic agent during uterine smooth muscle contraction. We investigated the effects of oxytocin and prostaglandins (PGE2 and PGF2 alpha) on phosphoinositide hydrolysis in the myometrium taken from non-pregnant and pregnant rabbits by measuring the accumulation of total inositol phosphates (IP). Oxytocin strongly, and PGE2 and PGF2 alpha slightly but significantly, stimulated IP production in both the non pregnant and pregnant myometria. Oxytocin more markedly accelerated the IP production in pregnant myometrium than in non-pregnant myometrium. However, IP production stimulated by PGE2 and PGF2 alpha was much the same in non-pregnant and pregnant myometria. The amount and time course of the increase in the production of the total IPs by oxytocin are quite different from those by PGs. It seems that the mechanism by which oxytocin stimulates phospholipase C is different from that of the PGs. It is suggested that transmembrane signalling pathways of phosphoinositide hydrolysis play an important role in the each mechanism. PMID- 8503704 TI - Scanning electron microscopy of human sperms after preparation of semen for in vitro fertilization. AB - Ultrastructural changes of human sperms after routine preparation for in-vitro fertilization were examined by scanning electron microscopy. Studies were performed with freshly ejaculated semen of 21 normozoospermic patients. Spermatozoa were analysed at 10000-fold (sperm head with acrosome, postacrosomal border and postnuclear cap) and 2500-fold (midpiece and endpiece of sperm tail) magnification. Compared with untreated specimens, slight membrane damage was found after routine washing and centrifugation procedures in swim-up preparations. However, on the basis of a score system for quantification of morphologic data, no statistically significant differences existed between untreated semen and swim-up preparations. We conclude that, with normozoospermic semen, the rate of ultrastructural damage attributable to sperm-washing procedures is too low to be of clinical consequence. PMID- 8503705 TI - Tamoxifen treatment of oligozoospermia: a re-evaluation of its effects including additional sperm function tests. AB - Because of previous contradictory results, we reevaluated the effects of tamoxifen on 29 men presenting with idiopathic oligozoospermia. To determine whether a possible increase in sperm concentration might be correlated with an improvement of sperm quality, the hamster ovum penetration (HOP) test and the hypo-osmotic swelling (HOS) test were included as additional tests of sperm function. Patients were treated with tamoxifen (20 mg/day) for 3 months. From 4 weeks until the end of the study, tamoxifen had a significant effect (P < 0.001) on blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2). Prolactin (PRL) concentrations were not altered significantly (P > 0.05). There was no significant improvement (P > 0.05) of conventional semen parameters (volume, concentration, motility, morphology), and of HOP and HOS test results. The lack of correlation between a rise in hormone levels and improvement of sperm quality suggests that tamoxifen is of questionable value in men with idiopathic oligozoospermia. PMID- 8503706 TI - The production of prostanoids and the identification of macrophages in human decidua vera tissue. AB - In decidual tissues of first trimester therapeutic abortions we have identified a large macrophage population that is stained by a specific antibody (Ki-M8). Also, we evaluated the capacity of decidual cells, obtained before and after labor, to synthesize prostanoids from radiolabeled arachidonic acid. Decidua collected after vaginal delivery produced significantly more prostaglandin (PG) F2 alpha, PGE2 and thromboxane (TX) B2 (7.4 +/- 1.3, 7.2 +/- 1.3, 11.7 +/- 1.1 pmol/mg protein/4 h, mean +/- SD, respectively) than did tissues from women who had caesarean sections (3.3 +/- 0.8, 1.4 +/- 0.5, 6.3 +/- 1.8 pmol/mg protein/4 h, respectively). Moreover, PGF2 alpha and PGE2 were rapidly converted to their 13,14-dihydro-15-keto-metabolites particularly in tissues obtained after vaginal delivery. All this lends further support to the proposition that decidual activation may be important in the onset of labor. PMID- 8503707 TI - Cervical pregnancy. A case report. AB - Cervical pregnancy is one of the most dangerous forms of ectopic pregnancy. This condition is frequently unsuspected before evaluation of the uterus and it is characterized by massive bleeding during that procedure. We report a case of cervical ectopic pregnancy diagnosed by ultrasound at 11 weeks' gestation and managed by emergency hysterectomy for severe hemorrhage occurring immediately after removal of the placenta. PMID- 8503708 TI - Neglected transverse lie with uterine rupture. AB - We present a case of neglected transverse lie with uterine rupture, which is rarely encountered in modern obstetric practice. The prominent clinical features, including uterine rupture and fetal death, are described. Treatment entails resuscitative measures and Cesarean delivery. PMID- 8503709 TI - [A pathological study of valvular dysplasia and attachment in Ebstein's anomaly]. AB - Forty hearts with Ebstein's disease of the tricuspid valve were studied in order to correlate dysplasia and attachment of tricuspid valve leaflets at the ventricular walls, atrialization of the right ventricle and fibrosis in this chamber. The correlation was positive. The right ventricular atrialization was directly proportional to leaflet attachment; the correlation in severity between leaflet attachment; the correlation in severity between leaflet attachment and dysplasia was positive in 45%. The right ventricular fibrosis was very frequent in the group with patent pulmonary valve (90%), and the contrary was in the group with pulmonary valve atresia (10%). The structural damage in the right ventricular wall was directly proportional to leaflet attachment in hearts with patent pulmonary valve (90%); in all of these hearts the anatomic annulus of the tricuspid valve was enlarged but in hearts with pulmonary valve atresia this feature only occurred in 10%. The specimens with atrioventricular discordant connexion, the anatomic annulus size, the degree of leaflet attachment, the dysplasia of the tricuspid valve as well as the fibrosis of the wall of the right ventricle were less severe compared with those hearts with concordant atrioventricular connexion. Ebstein's disease of the tricuspid valve is characterized by a disorder in the histodifferentiation of the right ventricle and the tricuspid valve which originates in great part from it. PMID- 8503710 TI - [Cardiogenic shock in acute myocardial infarct. Its coronary angioplasty treatment]. AB - Ventricular dysfunction is the most common cause of in-hospital death in patients with acute myocardial infarction. When cardiogenic shock is manifested the mortality is very high. Seven patients with cardiogenic shock complicating acute myocardial infarction were treated with emergency coronary angioplasty. Four patients required cardiopulmonary resuscitation (CPR), 2 intraaortic balloon pump support and one femoro-femoral bypass pump support during the coronary angioplasty. The angiography success rate was 86%. Two patients died, one in the catheterization laboratory and the other one 24 hours later. The hospital mortality was 29%. Of the patients who survived 4 are in functional class I and one in functional class II (NYHA). Coronary angioplasty therapy in patients with cardiogenic shock complicating acute myocardial infarction plays a decisive role in the reduction of mortality. PMID- 8503711 TI - [Gammagraphy of the myocardial perfusion in patients with the manifestations of post-coronary angioplasty ischemia]. AB - The evolution of 41 patients (36 men and 5 women), symptomatic or with positive ergometric tests post percutaneous transluminal coronary angioplasty, was studied to detect residual ischemia. Thallium-201 myocardial scintigrams were recorded six months after angioplasty. Stress induced ischemia in 22 (54%) cases (6 with multivessel disease and 11 with previous angina) was demonstrated. Coronary angiography was undertaken in 12 of ischemic cases, demonstrating restenosis in 7, atherosclerotic disease progression in 1 and no significant coronary lesions (with less 50% lumen vessel occlusion) in 4. The greatest lesions number (70%) corresponded to the left anterior descending coronary artery. In patients with restenosis, angina onset and ST segment depression with stress, were significant. The maximal load and the maximal heart rate percent achieved were less. Myocardial scintigraphy is a non-invasive method of great value to the post angioplasty residual ischemia diagnosis, principally in those patients in whom angina reappears. PMID- 8503712 TI - [Atherosclerotic ischemic cardiopathy in patients with dextrocardia in situs viscerum inversus]. AB - We describe the incidence, clinical, radiologic, electrocardiographic, echocardiographic and angiographic findings of two cases with dextrocardia in situ viscerum inversus with ischaemic heart disease. The first patient had coronary artery saphenous bypass graft and is currently asymptomatic with a negative maximal stress test. The other patient with diabetes mellitus and unfavorable coronary anatomy was not operated and is currently with stable angina on class II of the NYHA. The electrocardiographic, echocardiographic and angiographic strategies are commented. PMID- 8503713 TI - [Conduction disorders at multiple levels during the acute phase of a myocardial infarct: an electrophysiological study]. AB - Forty patients with a diagnosis of acute myocardial infarction (anterior 24, and inferior 16) were studied. Of these patients, 37.5% manifested second and third degree atrioventricular (AV) block as a complication; another 30% showed complete right bundle branch and left anterior hemiblock. Right bundle branch and left posterior hemiblock were evidenced in 12.5% of the subjects. There was 20% with complete left bundle branch block. Electrophysiologic studies were performed in all patients to assess the site of block. A direct relation was found between the surface ECG and the His bundle electrogram studies in patients with an inferior myocardial infarction and AV block, both procedures located the conduction disturbances at the AV node (suprahisian block), in contrast to patients with anteroseptal myocardial infarction whose surface ECG only showed bundle branch block or fascicular block. The His bundle electrogram registered multiple levels of AV block, 70% with troncular and infrahisian block that gave way to sudden AV block. The mechanism responsible for this block was considered to be a functional longitudinal dissociation of conduction system due to an acute ischemic injury of the His bundle, more than a sudden and simultaneous failure of all the bundle branch of His. We conclude that electrophysiologic studies are a useful procedure for identification of a group of patients with multiple AV conduction disturbances that have a less favorable prognosis than those with only suprahisian level of block. PMID- 8503714 TI - [A comparison and synergy in the treatment of essential arterial hypertension]. AB - Forty patients with mild or moderate essential hypertension were studied. They received daily doses of either 240 mg verapamil or 10 mg enalapril, as well as a placebo. Total duration of trial was 24 weeks: a "washout" period of 2 weeks, a treatment period of 6 weeks with one of the two drugs, another "washout" period of 2 weeks, and another treatment period of 6 weeks with the alternate drug. Those patients with persistence of diastolic blood pressure (DBP) above 90 mmHg received simultaneously both drugs for an additional period of 8 weeks. Patients were assigned alternately to one of the groups. When each drug was given during the first treatment period, DBP was reduced below 90 mmHg in 15 of 19 patients receiving verapamil, and in 12 of 20 that received enalapril. When the drugs were given during the second treatment period, DBP became normal in 16 of 19 patients receiving enalapril, and in all the 18 patients treated with verapamil. Three patients achieved normal DBP when received simultaneously both drugs. Two patients withdrew from the trial for personal reasons and one for experimenting cough as reaction to enalapril. There were no other undesirable side effects. Laboratory tests did not show changes. Both products were similarly effective. Synergy was shown by the improvement of patients unresponsive to either drug when given singly, but responding when both were given simultaneously. PMID- 8503715 TI - [The relationship between oxygen consumption and the the rate of rewarming during extracorporeal circulation with induced hypothermia]. AB - This study was performed to investigate the relation between total oxygen consumption (VO2) and the velocity of reheating in patients undergoing cardiopulmonary bypass with hypothermia. A total of 17 males undergoing this procedure were studied prospectively (mean age: 63 years, range: 52-72); during surgery they were cooled at 28 degrees C whole-body temperature. Before rewarming, patients were divided at random in two groups. Group A (n = 8) was reheated between 10 and 25 minutes, and group B (n = 9) between 26 and 50 minutes. In group A, VO2 expressed in ml.min-1 x m-2 increased from 76.6 +/- 6.99 at 28 degrees C until 100.0 +/- 6.72 at 34 degrees C; in group B increased from 68.4 +/- 4.55 until 129.1 +/- 4.73 at similar temperatures (analysis of variance: p < 0.01 at 28 degrees C). A greater VO2 in group B could indicate that slow rewarming would cause an even distribution of temperature with enough time for tissues to rid of their oxygen debt. PMID- 8503716 TI - [American trypanosomiasis (Chagas' disease). A clinico-serological survey in a rural community of Oaxaca]. AB - A survey at a rural community in Oaxaca, Mexico revealed 30 (29%) out of 104 people tested are carriers of anti-Trypanosoma cruzi antibodies. This high prevalence of seropositivity signals an important parasite circulation. We did not studied people under 15 years of age, therefore we can not identify transmission in this area. A concomitant study of 12 lead showed that those who are seropositive had more EKG abnormalities as a group. Such findings could indicate the parasitic disease impact on community health. PMID- 8503717 TI - [The cardiovascular effects of cocaine (II)]. PMID- 8503718 TI - [The mechanisms involved in the cardiac effects of serotonin]. PMID- 8503719 TI - [Ventricular remodelling]. PMID- 8503720 TI - [The reduction of the extension and severity of experimental myocardial infarct in pigs with growth hormone. The preservation of the microcirculation]. AB - Administration of hGH during the acute phase of experimental myocardial infarctions in pigs showed several aspects which clearly distinguished the treated group from the control one. In the first case the necrotic segment appeared considerably smaller than in the control group but also exhibit a qualitative different necrotic pattern in the histologic aspect, i.e. the infarcted area is shown itself reduced to isolated cells; scarce clusters of them interspersed where found within larger areas of preserved tissue. Affected cells have been defined as "injured fibres" according to their particular aspect which notably differs to the classic expected picture of a 25th day infarction and exhibits itself as an "arrested necrosis". A remarkable preservation of capillary vessels has also been found in the treated cases by a contrasting disappearance of the capillary bed in the control group. Ventricular contractility was also explored with ECHO B which showed significant differences between both groups: wall thinning of the ventricular wall in the affected area did not appear in treated cases and normal contractility in the same area reappeared a few hours after the infarction. Contractility was never restored in the control group. hGH main action is directed towards the preservation of the myocardial collagen matrix, helping to maintain the structural integrity of ventricular wall. There are, however, other possible effects on immunological aspects of the macrophages partially noticed, and to be disclosed in the future. PMID- 8503721 TI - Checklists for surgical pathology reports. PMID- 8503722 TI - Sudden death associated with aortitis and fibrosclerosing disease of the conduction system. PMID- 8503723 TI - Cocaine-associated dissection of the ascending aorta. PMID- 8503724 TI - Wristband identification error reporting in 712 hospitals. A College of American Pathologists' Q-Probes study of quality issues in transfusion practice. AB - The correct wristband identification of patients is essential to prevent acute, hemolytic transfusion reactions from incompatible transfusion. We compared wristband identification errors for 712 hospitals. Phlebotomists checked patient wristbands on 2,463,727 occasions, finding 67,289 errors; in 33,308 instances, patient wristbands were missing entirely. The median total error rate was 2.2%; 10% of participants had error rates of 10.9% or greater. Absent wristbands represented 49.5% of errors; multiple wristbands with different information, 8.3%; wristbands with incomplete data, 7.5%; erroneous data, 8.6%; illegible data, 5.7%; and patients wearing wristbands with another patient's identifying information, 0.5%. The monitoring for errors by phlebotomy staff was the most important policy associated with lower error rates. Initial placement of wristbands by nursing staff was the only policy associated with increased error rates. We conclude that wristband identification error rates depend on differences in hospital policy and procedure and should be responsive to quality improvement efforts. PMID- 8503725 TI - Probe technology for the clinical microbiology laboratory. AB - Molecular-based techniques, such as use of genetic probes, can greatly reduce turnaround time of the identification of some isolates in the clinical microbiology laboratory. For example, culture confirmation of an acid-fast bacillus such as Mycobacterium tuberculosis or Mycobacterium avium-intracellulare by a gene probe can be performed within hours of the isolation of the organism. Conventional methods might require more than 2 to 4 weeks for this identification. Identification of a mold, such as Histoplasma capsulatum, with a gene probe, can be done in less than 24 hours, with minimal growth available; conventional fungal identification takes 1 to 2 weeks or more. Whether a probe is used in the clinical microbiology laboratory depends on a number of factors including accuracy of the probe, cost, commercial availability, and ease of performance. In addition, the relevance of a more rapid result needs to be considered. A gene probe may be more specific than conventional methodologies, and this may increase its advantage. Direct specimen testing with probes is presently hampered by inadequate sensitivities. Prior amplification may decrease this limitation. It is hoped that methods will be available in the near future that provide amplification and probing of clinical specimens for laboratory diagnosis to be made within a short time following specimen collection. PMID- 8503726 TI - Manpower deficiencies in cardiovascular pathology. Implications for medical care of cardiovascular diseases. AB - The general shortage of pathology manpower has been well documented, but virtually no published data are available on cardiovascular pathologists. To address this situation, the Society for Cardiovascular Pathology surveyed all chairpersons of academic pathology departments, chiefs of academic clinical cardiovascular programs, including adult and pediatric cardiology and cardiovascular surgery, in the United States and Canada, regarding their perceptions of cardiovascular pathology manpower and the training and areas of expertise necessary for a competent cardiovascular pathologist. Of total respondents, 41% stated that their institution's department of pathology needed to add a cardiovascular pathologist, 39% of respondents replied that money and funding were available to hire an additional cardiovascular pathologist, yet only 19% stated that their institution intended to add a cardiovascular pathologist. In regard to career orientation, 77% of respondents wanted a cardiovascular pathologist capable of both diagnostic work and basic research. The survey results show a significant discrepancy between apparent institutional needs for cardiovascular pathologists and hiring plans, implying that there is a substantial shortage of cardiovascular pathologists. This deficiency in cardiovascular pathology manpower has important ramifications for the amount and quality of medical services that can be provided to clinical cardiovascular colleagues in an era of increasingly complex pathobiological information and interventional strategies in the prevention and treatment of cardiovascular diseases. PMID- 8503727 TI - Prolonged activated partial thromboplastin times and detection of the lupus anticoagulant. PMID- 8503728 TI - International normalized ratios. Has their time come? PMID- 8503729 TI - Biochemical biopsy of thyroid cysts vs cytologic diagnosis--which is preferable? PMID- 8503730 TI - The lupus anticoagulant. High incidence of 'negative' mixing studies in a human immunodeficiency virus-positive population. AB - We identified 100 patients (51 males and 49 females) as having the lupus anticoagulant. The following diagnoses were found in the patient population: human immunodeficiency virus positivity, 20%; systemic lupus erythematosus, 10%; prolonged preoperative activated partial thromboplastin time (APTT), 10%; procainamide hydrochloride-induced inhibitor, 9%; deep vein thrombosis, 6%; seizure disorders/epilepsy, 5%; and miscellaneous conditions, 40%. Identification was based on a prolonged APTT (> 40 seconds) that normalized with increased phospholipid concentrations and/or a prolonged Russell viper venom clotting time patient-control ratio of 1.20 or greater. In 68 cases (group 1), patient plasma prolonged the APTT of normal plasma in a 1:1 mixing study. However, in 32 cases (group 2), no such prolongation was observed. There was a significant difference between presenting APTTs in patients from group 1 (mean +/- SD, 58.29 +/- 13.30 seconds) compared with that in group 2 (mean +/- SD, 47.93 +/- 5.09 seconds). Furthermore, 66% of group 1 patients had elevated anticardiolipin antibody titers compared with only 41% in group 2. Of the 32 patients in group 2, 16 (50%) were positive for human immunodeficiency virus. We concluded that the investigation of a lupus anticoagulant should not be abandoned because patient plasma does not prolong the APTT of normal plasma in a mixing study, especially in a human immunodeficiency virus-positive population. PMID- 8503731 TI - Standardizing the prothrombin time. Calibrating coagulation instruments as well as thromboplastin. AB - Recently, indications for anticoagulation with warfarin have increased, prothrombin time (PT) monitoring at offices and homes has become available, and the international sensitivity index (ISI) has been recognized as a means of adjusting for differences in thromboplastins to standardize warfarin sodium dosing. However, different coagulation instruments may yield differences in PTs even after correcting for the ISI by means of the international normalized ratio (INR) (INR = [PT measured ISI/PT normal]). Because the PTs and INRs from our Anticoagulation Clinic (portable PT monitor, ISI = 2.04, normal PT = 12.0 seconds) differed from the hospital reference laboratory (ISI = 2.01, normal PT = 12.0 seconds) despite nearly identical ISIs and equivalent control or normal PTs, we systematically compared the two systems. During a 3-month period, we studied two groups of 50 consecutive patients who had been receiving a stable dose of warfarin. After a single venipuncture, PTs and INRs were measured independently, and regression lines were calculated. Within each group, the results from the different instruments were not identical, but they were highly correlated. In comparing INRs, the regression lines for the separate and combined groups were as follows: group 1 monitor INR = 0.49 reference INR + 0.81, r = .94; group 2 monitor INR = 0.57 reference INR + 0.86, r = .88; and combined monitor INR = 0.49 reference INR + 0.95, r = .89. Only 82% of the differences for all samples were within 1.0 INR units. We concluded that the instrumentation effect may be clinically meaningful, and coagulation instruments as well as thromboplastins should be calibrated to standardize warfarin therapy. PMID- 8503732 TI - Reticulated platelets in the evaluation of thrombopoietic disorders. AB - The laboratory diagnosis of immune platelet destruction has relied predominantly on the presence or absence of megakaryocytes in bone marrow. Recently, examination of peripheral blood platelets for high RNA content (reticulated platelets) or for elevated levels of platelet-associated IgG have been suggested as less invasive diagnostic tests. We used thiazole orange fluorescence labeling to determine the percentage of circulating reticulated platelets and two antibodies with different specificities directed against human IgG to measure platelet-associated IgG by flow cytometry in 59 patients with either immune thrombocytopenic purpura (n = 23) or chemotherapy-induced thrombocytopenia (n = 36). The percentage of reticulated platelets in patients with immune thrombocytopenia was significantly increased (38.6% +/- 27.4% [mean +/- 1 SD]), compared with patients receiving chemotherapy and normal subjects (7.2% +/- 3.3% and 2.9% +/- 2.2%, respectively). However, 17% of patients with immune thrombocytopenia had reticulated platelet values in the range observed for normal subjects and for patients with chemotherapy. Although one third of patients with immune thrombocytopenia had very high platelet IgG levels, the majority could not be distinguished from patients receiving chemotherapy solely on this basis. Combining the reticulated platelet determination with the IgG data did not improve the sensitivity or specificity of the reticulated platelet determination alone. We conclude that a flow cytometric assay for reticulated platelets is a better discriminant than flow-measured platelet IgG for diagnosing immune platelet destruction. We further postulate that the subset (17%) of patients with immune destruction who have relatively low percentages of reticulated platelets may represent patients with an inappropriately low thrombopoietic response. PMID- 8503733 TI - Decentralized testing for prothrombin time and activated partial thromboplastin time using a dry chemistry portable analyzer. AB - Previous work has established the precision and accuracy of a portable blood coagulation analysis system using paramagnetic particles contained in a dry reagent on a disposable test card. We examined the deployment of this technology in decentralized hospital settings and compared test results obtained in the surgical intensive care unit, coronary care unit, and outpatient cardiology clinic with those obtained in the central laboratory. Nursing personnel were instructed in the use of the system, and quality control testing was performed daily by the laboratory staff. In the intensive care units, patient subjects included those on whom tests of prothrombin time and activated partial thromboplastin time had been ordered. Immediate determinations were performed by the intensive care unit nursing staff on the same citrated, whole-blood samples that were subsequently sent to the central laboratory. In the outpatient cardiology clinic, fingerstick blood samples were obtained for prothrombin time determinations with the dry chemistry system. Paired prothrombin time samples obtained by venipuncture were run in the hospital laboratory. The study involved multiple users, multiple locations, two lots of activated partial thromboplastin time cards, and several different instruments, over an extended period. Correlation coefficients between the dry chemistry system and the hospital laboratory under these conditions were in an acceptable range in all sites studied. We concluded that, with appropriate training and quality assurance, the dry chemistry system provides an acceptable alternative to the hospital laboratory for prothrombin time and activated partial thromboplastin time determinations. PMID- 8503734 TI - A clinical study monitoring low-intensity anticoagulant therapy with a standard sensitivity thromboplastin. AB - The ability of the prothrombin time to measure the anticoagulant effect of warfarin sodium varies depending on the particular tissue thromboplastin used in performing the test. Based on studies using sensitive thromboplastins, lower therapeutic ranges of anticoagulation are recommended. The adequacy of monitoring therapy in this lower range with the relatively insensitive thromboplastins commonly used in North America is unestablished. This 16-month prospective study used a standard North American thromboplastin to monitor 157 anticoagulated patients treated in a low therapeutic range. Of the 1734 prothrombin times generated, 876 (56%) were therapeutic, with 400 (23%) below and 458 (26%) above the therapeutic range. These results are comparable with those published in trials in which more sensitive thromboplastins were used in a similar therapeutic range. We conclude that standard North American thromboplastins are adequately suited to monitor therapy in this lower range. PMID- 8503735 TI - Effect of blood transfusion on serum iron and transferrin saturation. AB - The effect of transfusion of packed red blood cells on serum iron level, total iron-binding capacity, and transferrin saturation was studied. Samples of blood from 37 hemodynamically stable patients were obtained for analysis at various intervals following the transfusion of packed red blood cells. In 10 patients with possible iron deficiency, a significant rise in serum iron level and transferrin saturation occurred during the 24 hours following transfusion, which persisted at a marginally significant level up to 36 hours. In the remaining 27 patients, a significant rise was also noted in serum iron level and transferrin saturation results, but the rise did not persist beyond the 24 hours after transfusion. No change in total iron-binding capacity was noted in either group. These data show that the diagnosis of iron deficiency (based on a transferrin saturation of < 0.16) might be missed if iron studies are performed on patients within 24 hours following packed red blood cell transfusion. Therefore, if serum iron studies are obtained for patients suspected of having iron deficiency anemia, these studies are best done on blood samples obtained before blood transfusion. PMID- 8503736 TI - Biochemical analysis of thyroid cyst fluid obtained by fine-needle aspiration. AB - Despite the relatively ready availability of thyroid cyst fluid specimens, little has been published on their biochemical composition. We measured the concentrations of 18 analytes in thyroid cyst fluid specimens from benign (n = 17) and malignant (n = 3) lesions and in homogenates of normal thyroid tissue (n = 5). The concentrations of an additional five analytes were measured in selected cyst fluid specimens only. Compared with normal human serum specimens, we found that in thyroid cyst fluid specimens the activities of acid phosphatase, aspartate aminotransferase, amylase, and lactate dehydrogenase, and the concentrations of iron and total bilirubin were highly increased. The concentration of glucose was low. The gross appearance of the fluids and the presence of certain analytes were consistent with a hemorrhagic origin of most of the benign and malignant cyst fluid specimens. Other biochemical markers, however, indicated colloidlike features and/or an admixture of thyroid tissue components to the cyst fluid. Although we have limited data for cyst fluid specimens from malignant thyroid lesions, we found no evidence that the results of any of the common biochemical tests would distinguish benign from malignant lesions. PMID- 8503737 TI - Prognostic factors in follicular carcinoma of the thyroid. AB - Although there are numerous publications on the nomenclature, morphological diagnostic criteria, and prognostic factors of follicular carcinoma of the thyroid, these issues remain controversial. We present the findings of a retrospective and comparative study of 82 patients who underwent thyroid surgery for thyroid neoplasms. Of these patients, 58 had follicular carcinoma, 12 had atypical adenoma, and the remaining 12 patients had adenoma with partial capsular invasion in the surgical specimen. The goal of the study was to determine diagnostic criteria and prognostic factors in follicular carcinoma. Our results showed that encapsulated thyroid follicular neoplasms should be considered malignant when they demonstrate total capsular invasion and/or vascular invasion. Statistical analysis of the cases of follicular carcinoma showed that higher morbidity rates were seen in the patients with metastasis at the time of diagnosis, with extensively invasive tumors, with age older than 35 years, and with tumors with simultaneous vascular and capsular invasion. The accumulated survival rate over 5 years based on mortality was 91%, and based on morbidity it was 71% (84% for patients with encapsulated tumors and 56% for patients with extensively invasive tumors). In the univariate survival study based on morbidity, we found a relationship with the following parameters: metastasis at the time of diagnosis, grade of local invasion, presence of capsular and vascular invasion, cellular atypia, histologic pattern (insular vs others), presence of thyroid nodule, and age of the patient at the time of diagnosis. In the multivariate survival study based on morbidity, the factors that showed prognostic value were metastasis at the time of diagnosis, grade of local invasion, and age of the patient at the time of diagnosis. PMID- 8503738 TI - Dense fibrosis. Another diagnostic criterion for papillary thyroid carcinoma. AB - The follicular variant of papillary thyroid carcinoma poses a diagnostic problem when optically clear nuclei cannot be clearly identified. Grooved nuclei, though highly specific, are often difficult to identify among the typically overlapping nuclei of the papillary carcinoma. In the frozen sections, both characteristics are usually not seen. The present study attempted to analyze the association between dense, and frequently hyalinized, fibrosis and papillary carcinoma to assess the possibility of using this finding as another diagnostic criterion for this type of thyroid carcinoma. Histologic slides of 37 papillary and 28 follicular carcinomas of the thyroid were reviewed. The presence of dense fibrosis within the tumor masses was recorded, while peripheral fibrosis was ignored. The proportion of papillary carcinoma showing fibrosis within the tumor mass was compared with that of the follicular counterpart. The odds ratio was calculated, and chi 2 with Yates' correction was computed for statistical significance. Thirty-three (89.2%) of 37 cases of papillary carcinoma showed dense fibrosis within the tumor masses, giving an odds ratio of 37.95 compared with the follicular type. The association is very strong and highly significant. It is concluded that dense fibrosis within a malignant tumor of the thyroid can be used as another diagnostic criterion of papillary carcinoma, especially when other classic criteria are absent or inconspicuous. PMID- 8503739 TI - Apocrine adenocarcinoma arising in cystic teratoma of the ovary. AB - We present a rare case of an apocrine adenocarcinoma arising in a mature cystic teratoma of the ovary. The patient, a 41-year-old woman, was admitted to the hospital with low back pain and hypermenorrhea. A unilocular cystic tumor, measuring 5.5 x 5.0 cm in diameter, was found in her right ovary, and was removed. The tumor contained a mural nodule, measuring 8 x 7 mm in diameter. Microscopically, the unilocular cystic tumor was a teratoma consisting of mature cutaneous tissue with numerous hairs. The mural nodule was composed mostly of cords of epithelial cells with an infiltrative fashion and anastomosing tubular structures, which were lined partly by cells with eosinophilic cytoplasm and decapitation secretion. The cytoplasm contained iron granules as well as granules that were stained with periodic acid-Schiff, with and without diastase digestion. PMID- 8503740 TI - Triploid abortus presenting as an ectopic pregnancy. AB - In this article we present a case of an ectopic gestation having morphologic features of a partial hydatidiform mole and demonstrating triploidy by flow cytometry in a patient presenting at 9 weeks' gestation. We include brief comments on partial hydatidiform mole. PMID- 8503741 TI - Perineurioma of the kidney. Report of a case with histologic, immunohistochemical, and ultrastructural studies. AB - We report a perineurioma of the kidney. A 66-year-old woman had a renal mass discovered as an incidental finding during the evaluation of hypertension and proteinuria. This neoplasm radiographically mimicked renal cell carcinoma, but the diagnosis of perineurioma was confirmed with histologic and ultrastructural studies. Perineurioma is a recently described, rare, benign tumor of the peripheral nervous system composed of perineurial cells. Histologically, the differential diagnosis includes low-grade fibromyxoid sarcoma and other myxoid tumors. PMID- 8503742 TI - The evolution of modern scientific laboratories. An address delivered at the opening of the William Pepper Laboratory of Clinical Medicine, Philadelphia, December 4, 1894. PMID- 8503743 TI - The William Pepper Laboratory. Commentary on the address given by William Welch at its opening on December 4, 1895. PMID- 8503744 TI - Confounds of insensitivity and blind luck: statistical conclusion validity in stroke rehabilitation clinical trials. AB - We present theoretical analyses of some infrequently considered consequences of low power and quantitatively review power in 36 stroke rehabilitation clinical trials with multiple outcome variables. We demonstrate that low power affects the proportion of false alarms (type 1 errors) in the literature and probability of replication, not only the ability to detect true intervention effects; and that these consequences of low power are modulated by the probability that effective interventions have been preselected for study via theory and prior evidence. interventions have been preselected for study via theory and prior evidence. Rehabilitation trials showed low power to detect small, medium, or large treatment effects at alpha = 0.05 (0.09, 0.33, and 0.69, respectively). Effect sizes were generally small with adverse consequences on power. As expected, sample size was an important determinant of power. Power was lower for motor/reflex measures due to differences in sample sizes rather than effect sizes. These results and the conceptual analyses predict and address conflicting conclusions from stroke rehabilitation clinical trials. PMID- 8503745 TI - Relationships between impairment and physical disability as measured by the functional independence measure. AB - This study was conducted to scale the Functional Independence Measure (FIM) with Rasch Analysis and to determine the similarity of scaled measures across impairment groups. The results show that the FIM contains two fundamental subsets of items: one measures motor and the second measures cognitive function. Rasch analysis of the Uniform Data System for Medical Rehabilitation patient sample yielded interval measures of motor and cognitive functions. The validity of the FIM was supported by the patterns of item difficulties across impairment groups. Adequate clinical precision of the FIM was demonstrated, though suggestions for improvement emerged. The frequency of misfit between patients and the performance scales varied across impairment groups, but was acceptable. The results of this project will enable clinicians and researchers to plan cost-effective treatment by providing a valid measure of disability. PMID- 8503746 TI - Pastoral needs and support within an inpatient rehabilitation unit. AB - Because patients reported concerns regarding the adequacy of pastoral service delivery during their inpatient rehabilitation hospitalization, a study was performed to ascertain the patient's pastoral needs and the extent of pastoral services provided. After discharge from the inpatient rehabilitation hospital, patients were surveyed as to their perceived religious and spiritual needs, as well as to the extent of religious, spiritual, and pastoral services provided during their inpatient stay. The majority of responders (74%) reported their religious and spiritual beliefs were important. Forty-five percent of responders indicated not enough attention was repaid to their religious or spiritual needs, whereas only 1% felt that too much attention was paid. A majority of patients (54%) desired pastoral visitation. Other needs were elicited, including expanded pastoral services, increased staff empathy for the patient's spiritual and religious needs, and improved availability of church or synagogue services or sacraments. Many Jewish patients reported concerns of being punished by God, whereas Christian patients were concerned that God was unaware of their personal needs. Some responders, regardless of personal faith, were also troubled with fears of death, God's failure to heal, and loss of purpose in life. There is a clear need to establish a mechanism to identifying the religious and spiritual needs of each individual patient. These needs must be considered with both sensitivity and compassion by all members of the rehabilitation staff. The rehabilitation facility must also develop a mechanism to identify pastoral care resources available within the hospital and local community, and to assure that the patient's needs are addressed. PMID- 8503747 TI - Current perceptions of rehabilitation professionals towards mild traumatic brain injury. AB - There has been long-standing controversy in the medical literature and increasing interest within the rehabilitation field in mild traumatic brain injury and postconcussion syndrome. The Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine conducted an opinion survey to analyze the perceptions of rehabilitation professionals towards patient's with these problems. The survey initially compared response patterns of rehabilitation personnel to two earlier identical surveys made with a group of neurosurgeons and a group of neuropsychologists. As a group, rehabilitation professionals tend to have perceptions of mild traumatic brain injury that are similar to those of neuropsychologists. The survey also included a group of questions developed to analyze specific issues among rehabilitation professionals related to symptomatology, persistence, and treatment. The most salient findings concluded that rehabilitation providers: (1) want a grading system associated with the term to designate injury severity, symptom severity, and level of functional impairment; (2) most frequently use neuropsychologists in assessment and treatment of these patients; (3) report cognitive deficits as the most common symptom, followed by irritability and somatic complaints; (4) when medications are used, most frequently use antidepressants; (5) typically follow these patients anywhere from six to 18 months postinjury; and (6) report that most patients make a complete functional recovery, though there is a substantial proportion (about 25%) who do not. Implications drawn from the survey include that there is a need to better define the term and its associated features and that there is a substantial group of patients who remain at least partially functionally disabled and present a major challenge to the rehabilitation community. PMID- 8503748 TI - Severity of pediatric traumatic brain injury and neurobehavioral recovery at one year--a cohort study. AB - As part of an ongoing longitudinal cohort study of children with mild, moderate, and severe traumatic brain injury and their matched controls, the neurobehavioral status of 94 case-control pairs was assessed one year after initial postinjury testing. There was a statistically significant dose-response association of severity with performance in all six domains of neurobehavioral functioning (intelligence, adaptive problem solving, memory, academic performance, motor performance, and psychomotor problem solving) with Spearman correlation coefficients of up to -.35, p < .001. The strongest correlations between severity and outcome were in the domains of intelligence, academic performance, and motor performance. Recovery over the year was also dependent on the severity of brain injury. Because mildly injured cases had negligible initial deficits, recovery was not at issue. However, for moderately and severely injured children, the degree of initial impairment was related to the magnitude of both recovery and residual deficit. Results showed that the use of population normative values to evaluate impairment was misleading. Although the mean scores of all severity groups fell within the normal range of standardized tests, the means for the moderately and severely injured were substantially below those of their matched controls on many tests. PMID- 8503749 TI - Occupational and educational achievements of head injured Vietnam veterans at 15 year follow-up. AB - Little is known about the long-term affects of head injury on achievement. The post-injury educational and occupational achievements of 520 survivors of penetrating head injury in Vietnam (and 85 uninjured controls) were examined 15 years after injury. Most patients (82%) had used Veterans Administration educational benefits to return to school, and many of those (64%) had achieved degrees. Return to work was strongly related to level of educational achievement, particularly among the most severely disabled. Though only 56% of the head injured were gainfully employed, the occupational distribution of those who were working differed little from uninjured controls, or the male labor force. Severity of injury affects educational achievement and return to work, but not the occupational distribution of those who do manage to return. Even the most severely injured can sometimes achieve high educational and occupational levels. PMID- 8503750 TI - Sensory loss in stroke patients: effective training of tactile and proprioceptive discrimination. AB - Although somatosensory loss following stroke is common, with negative consequences for functional outcome, studies of existing somatosensory retraining programs are limited by theoretical weaknesses, poor methodology, and negative findings. We, therefore, developed a new program for stroke patients and investigated its effect on tactile discrimination in four AB, single-case quasi experiments and its effect on tactile and proprioceptive discrimination in four multiple-baseline experiments. Training involved specific, graded discrimination tasks, attentive exploration of stimuli with vision occluded, deliberate anticipation, and quantitative feedback. Graphic and statistical interrupted time series analyses indicated that treatment produced improvements in seven of eight tactile time series and all four proprioceptive time series. Baseline improvement in one tactile time series prevented unequivocal evaluation of treatment effect. Improvements were clinically significant, discrimination in the affected hand becoming comparable to the other hand and normal performance. Therapeutic effects were maintained at 3-month to 5-month follow-up tests. PMID- 8503751 TI - Task-specific physical therapy for optimization of gait recovery in acute stroke patients. AB - A randomized controlled pilot trial was conducted to estimate the effects of early, intensive, gait-focused physical therapy on ambulatory ability in acute, stroke patients. Twenty-seven patients with middle cerebral artery infarct of thromboembolic origin confirmed by computed axial tomography scan were stratified and randomly assigned to the experimental group, to a control group that received early, intensive and conventional therapy, or to a group receiving routine conventional therapy that started later and was not intense. Assessments at entry, six weeks, and three and six months by independent evaluators permitted comparisons with reference to clinical measures of motor performance, balance, and functional capacity, and laboratory measures of gait movements. Group results at six weeks demonstrated that gait velocity was similar in the two conventional groups thereby eliminating the timing of the interventions as an important factor. At that point, gait velocity was faster in the experimental group. The difference translated into a moderate effect size of 0.58. The time dedicated to gait training but not to total therapy time was correlated (rs = 0.63) to gait velocity. This effect disappeared at three and six months after stroke. These pilot results justify planning a large trial to test the effectiveness of a therapeutic protocol that focuses on early and intense gait therapy in an effort to facilitate early ambulation following stroke. PMID- 8503752 TI - Predictors of falls among right-hemisphere stroke patients in the rehabilitation setting. AB - The purpose of the study was to examine neuropsychological and general medical risk factors for falls among a high-risk patient group in an inpatient rehabilitation setting. The sample consisted of 32 nonambulatory males who had sustained a right-hemisphere stroke (R-CVA). The Fall Assessment Questionnaire (FAQ) was introduced as a measure of known risk factors for falls in an inpatient setting. Neuropsychological assessment included measures of attention, perceptual deficits, hemispatial neglect, and impulsivity. A predictive model generated using multiple regression found that the FAQ combined with a measure of behavioral impulsivity successfully predicted fall status in 78% to 81% of cases, depending upon the cutting score used (p < .003). R-CVA patients who fell were more impulsive (p < .001) and received higher FAQ scores (p < .001). Perceptual deficit as measured by the Rey-Osterreith Complex Figure and general inattention as measured by Digit Span (reverse) were associated with falls (p < .04); however, they did not add to the model predicting which of the R-CVA patients would fall. It was suggested that impulsivity may act as an important mediating factor in determining individual risk for fall. PMID- 8503753 TI - Physical condition, activity pattern, and environment as factors in falls by adult care facility residents. AB - This study surveyed 294 fall incident reports made over a three-year period concerning 95 residents in an adult care facility. We determined the frequencies of fall location, time of day or night, and assessed the precipitating factors from fall descriptions made by residents and/or their care givers. We found that 57% of the falls occurred in the residents' rooms, with private or shared bathrooms as the next most frequent locus. Precipitating factors were surveyed; 50.3% of the fall descriptions implicated environmental features (pieces of furniture were most frequently mentioned), the physical condition of the resident contributed to 24.3% of the falls, and specific physical activities were implicated in 7.9% of the falls. Multiple factors accounted for 6.5% of the total falls. In 17% of the cases, no clear indication of cause was found. Unsafe environments have been implicated as a fall risk factor. Despite adaptations to lessen environmental hazards, a large number of reportable falls occurred in this facility, which was for elderly individuals who were in relatively good health commensurate with their age. PMID- 8503754 TI - Indices of verbal learning and memory deficits after right hemisphere stroke. AB - The deleterious effects of left hemisphere brain damage on language and verbal memory functions are well documented. However, limited attention has been paid to the effects of right hemisphere cerebrovascular accident (CVA) on these critical functions. Twenty-five right-handed, right hemisphere, stroke patients (RHS) were administered the California Verbal Learning Test (CVLT) and selected verbal, nonverbal, and orientation memory subtests of the Wechsler Memory Scale-Revised (WMS-R). An aphasia screening was also performed. The RHS patients performed significantly below the norm on all CVLT indices, whereas no differences were found between the RHS group and the WMS-R normative population for the story memory subtests. Study findings indicate that right hemisphere damage does affect performance of certain verbal memory tasks. Implications for inpatient treatment, post-acute care, and research with survivors of right hemisphere CVA are discussed. PMID- 8503755 TI - Cognitive-linguistic assessment of individuals with multiple sclerosis. AB - Four individuals diagnosed as having multiple sclerosis (MS) and four matched controls were assessed with the Arizona Battery for Communication Disorders (ABCD), a standardized battery of memory and cognitive-linguistic tasks. Subjects with MS and controls performed in an equivalent or nearly equivalent fashion for nine of the ABCD subtests. For five of the subtests (Object Description, Generative Naming, Concept Definition, Generative Writing, and Picture Description), subjects with MS performed substantially lower than the control subjects. Results of this pilot study suggest that portions of the ABCD may be useful in identifying profiles of memory, and cognitive-linguistic impairment among individuals with multiple sclerosis. Further research using a larger sampling of individuals with MS is needed to more fully assess the usefulness of the ABCD with this population. PMID- 8503756 TI - Countertransference and the multiple amputee patient: pitfalls and opportunities in rehabilitation medicine. AB - Current psychoanalytic literature on countertransference broadly defines the term as a helping professional's overall response to an individual patient. Reactions of rehabilitation professional to their traumatically injured patients can significantly impact on the patient's treatment as well as the individual therapist's and entire rehabilitation team's effectiveness. In this paper, a case is presented illustrating a process of understanding countertransference toward a multiple amputee patient. Implications for the rehabilitation team are also described. The analysis of a single case demonstrates how countertransference interpretation might be used as a vehicle to enhance understanding the patient and promote team effectiveness. PMID- 8503757 TI - Instrument development in the measurement of unsupported arm exercise endurance in normal adult subjects. AB - Many daily activities, from basic grooming to employment tasks, require adequate unsupported arm endurance (UAE). We developed an electromechanical device to measure UAE endurance. The purpose of this study was to standardize the instrument for two rates of arm motion, moderate and slow, in 18 normal adult subjects (FEVI = 3.7L +/- .78, FVC = 4.2L +/- .74, FEV1/FVC = 1.1 +/- .08). Exercise endurance limits, and the following metabolic, ventilatory, and sensation responses were determined at rest prior to exercise and at end-exercise limits for both rates of UAE:minute ventilation (Ve), tidal volume (VT), respiratory rate (RR), duty cycle (Ti/Ttot), oxygen uptake (VO2), carbon dioxide production (VCO2), inspiratory flow (VT/Ti), heart rate (HR), and visual analog scale measurements (VAS) of dyspnea (D), respiratory effort (RE), and arm fatigue (AF). Significance increases from baseline rest were shown at the endurance limits for both rates of UAE in: VO2, VCO2, Ve, VT, RR, VT/Ti, HR, VAS-D, VAS-RE, and VAS-AF. There were no changes in Ti/Ttot and SaO2 with UAE. Peak VO2, RR, Ve, VT/Ti, and VAS-D with moderate exercise were significantly greater than slow UAE; and there was a trend increase in peak HR for moderate as opposed to slow rate UAE. Despite these differences, the endurance time between the two rates of UAE were similar. These data provide standards against which UAE in COPD can be evaluated. PMID- 8503758 TI - Multichannel cochlear implantation in the rehabilitation of post-traumatic sensorineural hearing loss. AB - Although there is a 17% to 56% incidence of sensorineural hearing loss following head injury, to our knowledge cochlear implants have not been used in treatment of this problem in patients with cognitive deficits and aphasia. We report our experience with multichannel cochlear implantation in one such patient. The patient is a 26-year-old man with bitemporal lobe damage and T-11 paraplegia. The clinical profile showed emotional lability, perseveration of thought, impulsivity, good visuospatial orientation, and adequate use of oral and written language in conveying basic needs. Audiologic evaluation showed profound sensorineural hearing loss. Middle latency responses suggested intact thalamocortical pathways. The patient was provided with a multichannel cochlear implant with improvement in his speech recognition and functional skills. We conclude that the cochlear implant should be considered in patients with traumatic sensorineural hearing loss with relatively intact cognitive skills. PMID- 8503759 TI - Examining for myofascial trigger points. PMID- 8503760 TI - Coproporphyria versus multiple sclerosis. PMID- 8503761 TI - Toward a more complete society. PMID- 8503762 TI - Women as leaders in organized surgery and surgical education. Has the time come? AB - Women have entered medicine in large numbers during the past three decades, and are increasing their representation in some surgical fields at a rapid pace. Few women are found in senior roles in organized surgery or at the senior ranks of academic surgical faculty. Factors influencing this imbalance include family demands, sexism, and stereotypes that hinder the advancement of women into leadership roles. Strategies for correcting this imbalance include affirmative recruitment of women into surgery, particularly into academic surgical faculties; support systems, such as child care and adjustment of promotion and tenure timetables; mentoring; and programs of career development that emphasize skills in management as well as research and teaching. PMID- 8503763 TI - Women in surgery. An ancient tradition. AB - The heritage of women in surgery goes back to the dawn of Western civilization, to that strip of land lying between the banks of the Tigris and the Euphrates. This 5500-year history of women surgeons can be divided into three epochs: ancient history, the Middle Ages, and modern times. PMID- 8503764 TI - The early experience with laparoscopic cholecystectomy in Oregon. AB - OBJECTIVE: To obtain a profile of laparoscopic cholecystectomy (LC) across the state of Oregon with regard to the safety of the procedure, use of intraoperative cholangiograms, and requirements for granting surgeons privileges to perform LC and other laparoscopic procedures. DESIGN: Single-mailing survey to surgeons and chiefs of surgery in Oregon. SETTING: The state of Oregon. STUDY PARTICIPANTS: Surgeons and chiefs of surgery in Oregon. INTERVENTION: None. MAIN OUTCOME MEASURE: Numbers of procedures performed, deaths, complications, and requirements for surgical privileges. RESULTS: Sixty-nine percent of surgeons returned the questionnaire, as did 53% of the chiefs of surgery. Four deaths (0.04%), 244 complications (2.5%), and 27 bile duct injuries (0.28%) were reported in 9597 patients undergoing LC. Most surgeons (55%) obtained intraoperative cholangiograms routinely. Requirements for the privilege to perform LC varied among hospitals. Although the accuracy of this self-reported survey is uncertain, the results agree with those of other reports published to date. CONCLUSION: Laparoscopic cholecystectomy is being performed with acceptable safety, although the process of granting surgeons the privilege to perform this and other "new" laparoscopic procedures should be standardized according to established guidelines. PMID- 8503765 TI - The Association of Women Surgeons. A historical perspective 1981 to 1992. PMID- 8503766 TI - Jonasson, Braunwald, and Morani. Three firsts in American surgery. AB - The lives of three extraordinary surgeons who were among the earliest women in American surgery are chronicled herein. No written account can ever accurately reflect the hardships they suffered, or provide a true measure of their courage. Despite the support of colleagues, friends, and family, each crossed the new frontiers alone, in the face of great adversity. They survived, they endured, and ultimately they triumphed. What each has given back to her chosen profession has repaid, many times over, the training often reluctantly given. What each has conferred to those who come after is the conviction that it can be done and the strength to follow. PMID- 8503767 TI - Animal models for colon carcinogenesis. AB - Recent identification of genetic alterations in colon polyps and tumors has allowed construction of a hypothesis for the molecular basis of colon carcinogenesis. The consistency of observed genetic changes has inspired enthusiastic anticipation of new diagnostic tools and interventions for colon cancer. Appropriate animal models are crucial to the testing of molecular postulates as well as the development of markers and therapies for colon carcinogenesis. We discuss herein the various animal models that are currently used for the study of colon cancer as well as those that hold promise for the future. The contributions, drawbacks, and potential uses for the chemical carcinogen model, the multiple intestinal neoplasia model, transgenic animals, and the reconstruction model in the study of colon carcinoma are presented. PMID- 8503768 TI - Is full-time surgical research a career for a woman? AB - In this review of a 25-year experience in full time surgical research, special emphasis is placed on the suitability of such a post for a female surgeon and on the particular skills that a woman can bring to such a position. PMID- 8503769 TI - Surgery 2001. Twilight of the gods. AB - Statistics documenting the relentless rise of women in American medicine, primary care specialties, and surgery are presented. Representation of women in many surgical societies, on journal editorial boards, and in surgical texts does not appear to have kept pace. The participation of women surgeons in each of these activities ranges from 0.8% to 1.7%, equivalent to the percentage of women in general surgery before 1975. Comparison is made with women surgeons in an open national society (8.2%), an open regional society (6.9%), an open editorial board (7.5%), and a recently published textbook of surgery (8.2%). These proportions parallel the current 6.3% of women in general surgery and support the premise that women are at least as likely as their male colleagues to participate in the professional activities of the surgical establishment. During the waning years of the 20th century, ever-increasing numbers of qualified women will come forward to join the hierarchy of American surgery. PMID- 8503770 TI - Firearm injuries in girls and women. The unaddressed imperative. AB - OBJECTIVE: To describe the trends in firearm fatalities in California between 1987 and 1991 and the 153 firearm injuries in girls and women treated at the King/Drew Medical Center, Los Angeles, Calif, from September 1, 1991, to December 31, 1992. DESIGN: Retrospective study. SETTING: The study was conducted at the King/Drew Medical Center, a university-based county hospital, one of the major trauma centers in Los Angeles. PATIENTS: At the King/Drew Medical Center, 32 patients (21%) required at least one major procedure. Of the 16 patients who died, 14 (88%) died in the emergency department of wounds to the head (six patients), chest (five patients), and abdomen (three patients). The odds ratio of dying if injured in the head, face, or neck was 2.23, and in the abdomen, 1.0. Surgeons rarely probe for the underlying cause of injury. MAIN OUTCOME: The outcome has been a 2.28-fold increase in deaths in girls and women aged 10 to 19 years. RESULTS: Much of the violence against girls and women is perpetrated by those known to them. CONCLUSION: Firearms are the most frequently used weapon in female homicides. Firearm fatalities in women represent a significant problem among all ethnic groups. Trauma centers must take the lead in the collection of meaningful data to implement effective gender- and ethnic-specific violence prevention strategies. PMID- 8503771 TI - Female surgeons in the 1990s. Academic role models. AB - As part of a larger survey of the membership of the Association of Women Surgeons, data were collected to characterize the participation of women in academic surgery and surgical education. Of the 1500 members, 676 (45%) responded, and 318 of these respondents held a faculty appointment. Two hundred thirty-nine of the respondents' practices were based in a university or university-affiliated hospital. This sample was biased toward more academically motivated, upwardly mobile surgeons. Two hundred thirty-six of the respondents believed policies relating to tenure are unfair to women. Four hundred fifty three respondents reported having role models at some point in their career, half of whom were men. However, only 204 still had access to role models or mentors at the time of the survey. Six hundred thirty respondents believed that female medical students need successful female surgeons as role models. PMID- 8503772 TI - Occult hypoadrenalism in critically ill patients. AB - No clear criteria exist to rule out hypoadrenal shock by cosyntropin (alpha 1-24 corticotropin, a synthetic subunit of adrenocorticotropic hormone) testing in persons who have critical nonadrenal illness. Four patients in the surgical intensive care unit with critical multisystem disease and refractory high cardiac output, low vascular resistance shock had significantly diminished or terminated vasopressor requirements after institution of hydrocortisone sodium succinate infusion in doses simulating physiologic stress response (100 to 300 mg of hydrocortisone per day). In each case, cosyntropin testing revealed serum cortisol levels higher than those usually associated with hypoadrenal shock. Positive response was defined as maintenance of blood pressure with a decrease to less than 25% of baseline pressor requirements within 48 hours of treatment. We hypothesize a syndrome of functional hypoadrenalism in patients with multisystem critical illness and refractory shock responsive to glucocorticoid administration in doses simulating physiologic stress response despite cosyntropin stimulation test results that would rule out hypoadrenalism in a normal person. PMID- 8503773 TI - Liver transplantation for fulminant hepatic failure. AB - OBJECTIVE: The purpose of this study was to assess outcome after liver transplantation for fulminant (FHF) and subfulminant (SHF) hepatic failure and to determine the factors responsible for outcome. PATIENTS AND SETTING: Thirty-five patients who underwent 42 liver transplantations for FHF and eight patients who underwent eight liver transplantations for SHF at a large university medical center were followed up for 1 month to 5 years. OUTCOME MEASURES: Actuarial patient and graft survival for FHF and SHF were assessed and compared with the outcome for all patients who underwent liver transplantation at the same center over the same period (445 transplants in 420 patients). Patients were treated with intracranial pressure monitoring, aggressive measures to decrease intracranial pressure, and rapid transplantation. Functional status and recurrent disease were additional end points. RESULTS: One-year actuarial patient survival rates for FHF and SHF were 92% and 100%, respectively. Minor neurological sequelae were noted in two patients. Functional status was excellent. Posttransplant hepatitis was present in two patients with an original diagnosis of FHF and acute hepatitis B and in three patients with an original diagnosis of FHF and non-A, non-B, non-C hepatitis. CONCLUSION: Patients with FHF and SHF can achieve excellent results after liver transplantation. Rapid assessment of candidacy with monitoring of intracranial pressure and aggressive treatment for intracranial hypertension are thought to be essential in the outcome of these patients. PMID- 8503774 TI - Circulating and exudative polymorphonuclear neutrophil priming and oxidative capacity in anergic surgical patients. AB - OBJECTIVES: To examine the oxidative capacity of circulating and exudate polymorphonuclear neutrophils from reactive patients and anergic patients before surgery to determine why anergic patients have increased sepsis-related mortality once an infectious complication develops. DESIGN: Prospective in vitro patient study. SETTING: Tertiary care, major university teaching hospital. PARTICIPANTS: Surgical patients admitted for major elective gastrointestinal surgery. MAIN OUTCOME AND MEASURES: We used flow cytometry and the dye 2-7-dichlorofluorescein diacetate to measure hydrogen peroxide production of circulating and exudate polymorphonuclear neutrophils at baseline and after stimulation with Staphylococcus epidermidis. RESULTS: We found that polymorphonuclear neutrophils were primed in the intravascular space as evidenced by increased numbers of formyl-methionyl-leucyl-phenylalanine receptors, increased hydrogen peroxide production at baseline, and increased hydrogen peroxide production with stimulation. These results were more evident in the anergic patient. After exudation, anergic polymorphonuclear neutrophils lost most of their capacity to produce additional hydrogen peroxide. CONCLUSIONS: The data suggest that this intravascular priming adversely affected polymorphonuclear neutrophils during exudation, more marked in the anergic patient, and may contribute to the sepsis related mortality of the anergic patients. PMID- 8503775 TI - Cancer of the rectum. Where are we? Where are we going? PMID- 8503776 TI - Impact of exogenous insulinlike growth factor 1 on hepatic energy metabolism in burn injury. AB - BACKGROUND: Insulinlike growth factor 1 (IGF-1) has previously been demonstrated to improve the nutritional status of burned animals. The method by which it achieves this result has not yet been fully elucidated, but may be the result of alterations in hepatic metabolism. OBJECTIVE: To determine if IGF-1 is able to correct the burn-induced impairments in hepatic metabolic function. DESIGN: Seventy-two Sprague-Dawley rats were subjected to a sham burn (n = 24), or a 50% total body surface area scald burn (n = 48). Half the scald burn group received 3 micrograms/kg per day of IGF-1. The remainder received a placebo. The rats were sequentially assayed for multiple components of hepatic function. RESULTS: Insulinlike growth factor 1 corrected the burn-induced decrease in hepatic adenosine triphosphate concentration and prevented the burn-induced increase in hepatic ketone body levels. Insulinlike growth factor 1 was also able to prevent the burn-induced decrease in the hepatic acetoacetate-beta-hydroxybutyrate ratio. Since this ratio is directly proportional to mitochondrial redox potential this indicates that IGF-1 is also able to prevent the burn-induced impairment in hepatic redox potential. CONCLUSIONS: These data indicate that part of the previously demonstrated beneficial effect of IGF-1 in burn injury may be due to its ability to improve multiple components of hepatic metabolism. PMID- 8503777 TI - Human immunodeficiency virus exposure among medical students. PMID- 8503778 TI - Properties of a filamentous virus isolated from grapevines affected by corky bark. AB - A virus with highly flexuous filamentous particles c. 800 nm long, showing distinct transverse striations was isolated with high frequency (60%) by inoculation of Nicotiana occidentalis with sap from grapevine accessions indexing positive for corky bark. The virus, for which the name grapevine virus B (GVB) is proposed, has an ssRNA genome with mol. wt. of c. 2.5 x 10(6) Da (c. 7600 nt) and coat protein subunits with mol. wt. of c 23,000 Da. GVB has a very restricted herbaceous host range and was experimentally transmitted by the mealybug Pseudococcus ficus. The physicochemical and ultrastructural properties of GVB resemble those of closteroviruses. However, it is serologically unrelated to other grapevine closteroviruses including grapevine virus A, with which it shares some biological and physicochemical properties. PMID- 8503779 TI - Comparison of replication rates and pathogenicities between the SA14 parent and SA14-14-2 vaccine strains of Japanese encephalitis virus in mouse brain neurons. AB - The replication rates and pathogenicities of the SA 14 parent and SA 14-14-2 vaccine strains of Japanese encephalitis (JE) virus in neurons of the mouse brain following intracerebral inoculation were compared. All the mice inoculated with the SA 14 parent strain died within one week postinoculation (p.i.), whereas all the mice inoculated with the SA 14-14-2 vaccine strains survived without showing any signs of central nervous system (CNS) involvement. The virus titers of the mouse brains inoculated with the SA 14 strain reached progressively higher levels until day 5 when the animals died. On the other hand, the virus titers of the mouse brains inoculated with the SA 14-14-2 strain persisted at low levels for several days and could not be detected after 10 days. In the routine electron microscopical study, a majority of neurons in the mouse brains inoculated with the SA 14 strain contained virions and showed characteristic cytopathological changes in connection with viral replication. In the brains inoculated with the SA 14-14-2 strain, however, we failed to find neurons containing virions or showing characteristic cytopathological changes. In the alkaline phosphatase immunostaining of paraffin-embedded sections, a majority of neurons in the brains of mice inoculated with the SA 14 strain stained positively on day 5 p.i., but only a small number of neurons in scattered small foci stained positively in the brains inoculated with the SA 14-14-2 strain. The immunogold staining of Vibratome sections also revealed the identical patterns; moreover, electron microscopical examination of the immunopositive foci of the brain inoculated with the vaccine strain revealed neurons that contained virions in dilated cisternae of rough endoplasmic reticulum (RER), indicating that the SA 14-14-2 strain also replicated, albeit poorly, in neurons. The present results showed that upon intracerebral inoculation into mice the SA 14 parent strain of JE virus grew vigorously in a large number of neurons, killing the animals, while the SA 14-14 2 vaccine strain grew poorly only in a small number of neurons without causing mortality. Possible mechanisms involved in the alteration of pathogenicity between the SA 14 parent virus and the SA 14-14-2 vaccine virus are discussed. PMID- 8503780 TI - Ultrastructural studies on a chlorella virus from Germany. AB - This is the first report on the morphology and fine structure of chlorella virus Gottingen-1 (CVG-1), an European member of the newly approved family Phycodnaviridae, which infects certain unicellular, eukaryotic, exsymbiotic, green algae. CVG-1 are polyhedral particles 145-160 nm in diameter. The capsid consists of two shells, apparently composed of ca. 7 nm subunits. Whereas the outer shell of the capsid appears to be icosahedral, the inner shell appears to be irregular underneath one vertex of the virion. In this vertex the inner shell is separated from the outer shell leaving a distinct space ("empty vertex") of unknown function. PMID- 8503781 TI - Antiviral effects of different CD4-immunoglobulin constructs against HIV-1 and SIV: immunological characterization, pharmacokinetic data and in vivo experiments. AB - The CD4 cell surface antigen belongs to the immunoglobulin superfamily and is the primary receptor for the human immunodeficiency virus 1 (HIV-1). The high affinity interaction between HIV-1 and CD4 is mediated by the viral envelope glycoprotein gp120. Recombinant soluble CD4 (rsCD4) has been shown in vitro to be an effective inhibitor of HIV-1 and HIV-2 propagation in lymphoid cells. A variety of antibody-like molecules were constructed, consisting of different parts of the extracellular domain of CD4 fused to immunoglobulin constant regions. The fusion proteins were expressed in mammalian cell lines and purified via affinity chromatography. The specificity and anti-viral effects of the different CD4-immunoglobulin constructs against HIV were analysed by different immunological tests, i.e., immunofluorescence, neutralisation and in vitro assays. In pharmacokinetic studies, differences were found in serum half-life between the four- and two-domain CD4 constructs in cynomolgus monkeys and between glycosylated and deglycosylated CD4-Fc constructs in rabbits. In two in vivo experiments using the four-domain CD4-Fc in SIV-infected macaques, no beneficial effects were observed. PMID- 8503782 TI - The coat protein genes of squash mosaic virus: cloning, sequence analysis, and expression in tobacco protoplasts. AB - Complementary DNA of the middle-component RNA of the melon strain of squash mosaic comovirus (SqMV) was cloned. Clones containing the coat protein genes were identified by hybridization with a degenerate oligonucleotide synthesized according to the amino acid sequence of a purified peptide fragment of the SqMV large coat protein. A clone containing of 2.5 kbp cDNA insert of SqMV M-RNA was sequenced. The total insert sequence of 2510 bp included a 2373 bp open reading frame (ORF) (encoding 791 amino acids), a 123 bp 3'-untranslated region, and a poly(A) region. This ORF is capable of encoding both the 42 and 22 k SqMV coat proteins. Direct N-terminal sequence analysis of the 22 k coat protein revealed its presence at the 3' end of this ORF and the position of the proteolytic cleavage site (Q/S) used to separate the large and small coat proteins from each other. A putative location of the N-terminal proteolytic cleavage site of the 42 k coat protein (Q/N) was predicted by comparisons with the corresponding coat proteins of cowpea mosaic virus, red clover mottle virus, and bean-pod mottle virus. Although the available nucleotide sequences of these viruses revealed little similarity, their encoded coat proteins shared about 47% identity. The identity of the encoded 42 k and 22 k peptides was confirmed by engineering the respective gene regions for expression followed by transfer into tobacco protoplasts using the polyethylene glycol method. Both SqMV coat proteins were expressed in vivo as determined by their reactivity to SqMV coat protein specific antibodies. PMID- 8503783 TI - T cell responses to synthetic peptides of herpes simplex virus type 1 glycoprotein D in naturally infected individuals. AB - To locate T cell determinants of glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1), proliferation assays of lymphocytes obtained from 10 healthy HSV seropositive individuals were performed using 34 overlapping gD peptides as antigens. Despite large differences between individual responses to the peptides both in number of stimulating peptides and gD regions, three regions (1-54, 110 214, and 290-314) induced a response in 50% or more of the HSV-seropositives. T cells were less frequently stimulated by peptides of region 210-294. No correlation was found between serological data and proliferative responses to the peptides. The diversity in T cell response to the peptides suggests a lack of immunodominance, implying that a single peptide/region of gD, or a combination of peptides, will not be sufficient to serve as a basis for a future HSV-1 vaccine. PMID- 8503784 TI - Spontaneous and induced host-range mutants of cyanophage N-1. AB - Optimal conditions for the induction of host-range mutants of cyanophage N-1 by acridine orange were established. Induced host-range mutants were isolated with a frequency of 0.1 to 4.0 x 10(-5) over a spontaneous mutation frequency of 0.2-3.6 x 10(-11). PMID- 8503785 TI - In vitro translation of rice dwarf phytoreovirus genome segments S4 to S10. AB - The individual synthetic plus-strand transcripts from full-length cDNAs of rice dwarf phytoreovirus genome segments S4 to S10 directed the in vitro synthesis of predominant polypeptides, whose migration positions in SDS-polyacrylamide gel indicated molecular masses of 83 k (P4), 89 k (P5), 56 k (P6), 58 k (P7), 43 k (P8), 49 k (P9), and 35 k (P10), respectively. P7 and P8 had the same mobilities as those of the structural proteins, supporting the previous observations. The other proteins (P4, P6, P10) as well as P9, which had been considered an outer capsid protein, are probably nonstructural proteins, since no polypeptides with similar migration behavior were found in a purified RDV preparation. It remains to be confirmed biochemically whether S5 encodes the outer layer protein. PMID- 8503786 TI - Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H5 and H7 subtypes. AB - The amino acid sequences at the haemagglutinin cleavage sites of 9 avian influenza A viruses of H5 subtype (5 high and 4 low pathogenicity for chickens) and 21 of H7 subtype (13 high and 8 low pathogenicity for chickens) were determined by direct RNA sequencing, PCR amplification sequencing or both. None of the viruses of low pathogenicity had multiple basic amino acids at the cleavage site. All highly pathogenic viruses had an insert of basic amino acids at the cleavage site, except A/chicken/Scotland/59 (H5N1) for which the multiple basic amino acids appeared as substitutions and not insertions. All highly pathogenic viruses examined conformed to the amino acid motif of R-X-R/K-R at the cleavage site which is considered to be essential for high pathogenicity in chickens, with the notable exception of highly pathogenic virus A/turkey/England/50-92/91 (H5N1) which had the sequence R-K-R-K-T-R adjacent to the cleavage site. PMID- 8503787 TI - Experiments on maternal and paternal transmission of Creutzfeldt-Jakob disease in mice. AB - No transmission of Creutzfeldt-Jakob disease in mice was observed in 75 offspring born to CJD agent-inoculated females or to normal females mated with inoculated males and in 19 normal offspring maintained by foster nursing with the inoculated mothers. The fertility of young adult female mice was lost by the 57th day after the inoculation, whereas the reproductivity of male mice was maintained over 106 days after the inoculation. PMID- 8503788 TI - Genetic and antigenic analysis of an equine influenza H 3 isolate from the 1989 epidemic. AB - The haemagglutinin (HA) gene from the equine influenza H3N8 isolate Suffolk/89 has been cloned by reverse transcription and polymerase chain reaction amplification. The nucleotide sequence of the HA gene was determined from two independently cloned copies of the gene and was found to be most closely related to recent American isolates supporting the idea that most isolates of equine H3N8 are evolving as a single lineage. When the predicted amino acid sequence of the Suffolk/89 HA was examined, changes had taken place in at least four of the major antigenic sites, A, B, C, and D when compared to the sequences of the isolates used in the current vaccines (Miami/63 and Fontainebleau/79). Surprisingly, when the Suffolk/89 isolate was tested in haemagglutination inhibition (HI) assays with a panel of six mouse monoclonal antibodies, no differences were observed between the Suffolk/89 and the Fontainebleau/79 isolates, suggesting that this panel of monoclonal antibodies may recognise a limited subset of the major antigenic sites. Three anti-HA horse heterohybridoma monoclonals were able to distinguish between the Suffolk/89 and Fontainebleau/79 viruses, demonstrating that the horse does recognise these isolates as being antigenically different. The results of the work suggest that the isolates used in current equine influenza vaccines may need updating. PMID- 8503789 TI - Haemostatic abnormalities in African swine fever a comparison of two virus strains of different virulence (Dominican Republic '78 and Malta '78). AB - African swine fever (ASF) virus strains cause haemorrhage by producing a variety of defects, which vary in severity from strain to strain. To distinguish the main haemostatic defects leading to haemorrhage, two groups of pigs were infected with moderately virulent (Dominican Republic '78) and less virulent (Malta '78) ASF virus strains. Mortality rate and severity of clinical observations were greater in pigs infected with DR '78 virus compared with pigs infected with Malta '78 virus. The animals became febrile from day 3 to 4 onwards at a time when the viraemia was high (10(7) to 10(8) HAD50/ml). No difference was found during the period observed in their pattern of viraemia or pyrexia. Thrombocytopenia developed in both groups but with different kinetics, suggesting two different mechanisms of sequestration of platelets. When coagulation tests were performed, significant abnormalities were found, including evidence for disseminated intravascular coagulation. These abnormalities were much less pronounced in the group infected with Malta '78. Antithrombin III activity did not change significantly in either group. Decreased plasminogen activity was found in the early phase of disease in DR '78 infected pigs. These results indicate that when haemorrhage does occur in DR '78 infected pigs, it is a consequence of more pronounced degrees of haemostatic impairment probably due to a marked endothelial injury and/or generation of procoagulant activity. PMID- 8503791 TI - Vitamin B12 deficiency neuropsychiatric damage in acquired immunodeficiency syndrome. PMID- 8503790 TI - Structure and expression in E. coli of the gene coding for protein p10 of African swine fever virus. AB - The gene encoding protein p10, a structural protein of African swine fever (ASF) virus, has been mapped, sequenced and expressed in E. coli. Protein p10 was purified from dissociated virus by reverse-phase HPLC, and its NH2-terminal end identified by automated Edman degradation. To map the gene encoding protein p10, a mixture of 20-mer oligonucleotides based upon a part of the amino acid sequence was hybridized to cloned ASF virus restriction fragments. This allowed the localization of the gene in fragment Eco RI K of the ASF virus genome. The nucleotide sequence obtained from this region revealed an open reading frame encoding 78 amino acids, with a high content of Ser and Lys residues. Several of the Ser residues are found in Ser-rich regions, which are also found in some nucleic acid-binding proteins. The gene coding for protein p10 has been inserted in an expression vector which contains the promoter for T7 RNA polymerase. The recombinant plasmid was used to produce the ASF virus protein in E. coli. The bacterially produced p10 protein shows a strong DNA binding activity with similar affinity for both double-stranded and single-stranded DNA. PMID- 8503792 TI - Another case of polymyositis after ciguatera toxin exposure. PMID- 8503793 TI - Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. AB - OBJECTIVE: To determine systematically central nervous system and systemic complications during the acute phase of adult bacterial meningitis. DESIGN: Prospective clinical study. SETTING: University referral center, Department of Neurology. PATIENTS: A total of 86 consecutive patients between the ages of 15 and 87 years who had bacterial meningitis. MEASUREMENTS: Central nervous system complications, including brain swelling, hydrocephalus, brain abscess, subdural empyema, or subdural effusion (using computed tomography) and cerebrovascular involvement (using cerebral angiography), systemic complications, including septic shock, disseminated intravascular coagulation, adult respiratory distress syndrome, or septic or reactive arthritis, and typical complications arising during intensive care therapy. RESULTS: Of the 86 adult patients with bacterial meningitis, complications developed in 43 patients. The major central nervous system complications included angiographically documented cerebrovascular involvement (15.1% of the patients [13/86 patients]), brain swelling (14.0% [12/86]), hydrocephalus (11.6% [10/86]), and intracerebral hemorrhage (2.3% [2/86]), while septic shock (11.6% [10/86]), adult respiratory distress syndrome (3.5% [3/86]), and disseminated intravascular coagulation (8.1% [7/86]) dominated among the patients with systemic complications. Seven patients had cerebral herniation, three with a lethal course. The overall mortality was 18.6% [16/86] and was 10 of 30 (3.33%) in pneumococcal meningitis. CONCLUSIONS: Clinical and autopsy studies showed that the major determinants for the lethal outcome were primarily central nervous system complications in six patients, systemic complications in five, and a combination of both in another five. The identification of the various complications and their time of expected occurrence may help to develop additional treatment regimens in bacterial meningitis in adults. PMID- 8503794 TI - Interictal metabolic anatomy of mesial temporal lobe epilepsy. AB - OBJECTIVE--To examine patterns of temporal and extratemporal regional interictal glucose hypometabolism in individual patients with unilateral mesial temporal lobe epilepsy (TLE). Previous reports disagree on which extratemporal areas can be hypometabolic in TLE. DESIGN--Case series of patients with TLE who underwent interictal fludeoxyglucose F 18 positron emission tomography, compared quantitatively with normal positron emission tomography. SETTING--Patients referred for surgical treatment of medically refractory complex partial seizures. PATIENTS AND OTHER PARTICIPANTS--Ten normal volunteers; 27 patients with TLE selected to exclude seizures of bilateral temporal or extratemporal onset. RESULTS--Regional hypometabolism occurred in 25 patients. Hypometabolic regions were ipsilateral to seizure onset and included lateral temporal (in 78% of patients), mesial temporal (70%), thalamic (63%), basal ganglial (41%), frontal (30%), parietal (26%), and occipital (4%). Specific patterns of temporal and extratemporal hypometabolism varied considerably across the TLE group. CONCLUSIONS--Any of the previously reported anatomic areas of hypometabolism can occur in individual patients with TLE. The prevalence of thalamic hypometabolism suggests a pathophysiologic role for the thalamus in initiation or propagation of temporal lobe seizures or in the interictal cognitive dysfunction of TLE. PMID- 8503795 TI - Juvenile myoclonic epilepsy. A review. AB - Juvenile myoclonic epilepsy is a common idiopathic generalized epileptic syndrome that occurs in 5% to 10% of patients with epilepsy. Despite this, it is still frequently unrecognized and misdiagnosed, even as epilepsy of focal onset. Juvenile myoclonic epilepsy usually responds well to treatment with appropriate anticonvulsants, and misdiagnosis often results in unnecessary morbidity. This article reviews the syndrome, including the clinical and electroencephalographic features, the misinterpretation of which contributes to misdiagnosis. PMID- 8503796 TI - Hereditary influences on cognitive functioning in older men. A study of 4000 twin pairs. AB - OBJECTIVE: To determine the contribution of genetic factors to cognitive functioning in older men. DESIGN: Cognitive testing by telephone interview in an epidemiologically defined population. PARTICIPANTS: 2077 monozygotic and 2225 dizygotic male twin pairs, all between the ages of 62 and 73 years, recruited from the National Academy of Sciences twin registry. MAIN OUTCOME MEASURES: The Telephone Interview for Cognitive Status--Modified total score and factor scores were analyzed. The Falconer heritability statistic and maximum likelihood estimates of genetic and environmental components were computed. RESULTS: Heritability of the total Telephone Interview for Cognitive Status--Modified score was estimated to be 30%. Shared environmental effects accounted for an additional 18% of the variance; most of this was related to years of education. Of the four cognitive factors derived, the language/attention factor had the highest heritability estimate. CONCLUSIONS: Genetic factors and educational achievement together account for almost half of the variance in the cognitive functioning of older men. Studies of the genetics of dementing illnesses need to consider the degree to which cognitive capacities are themselves under genetic control. PMID- 8503797 TI - Tibial muscular dystrophy. Late adult-onset distal myopathy in 66 Finnish patients. AB - OBJECTIVE: To clarify the classification of two previously reported groups of patients with anterior tibial distal dystrophy, to find additional patients with the disease, and to describe the clinical features of this disease. DESIGN: National survey of the records of patients with neuromuscular diseases in Finland. Findings of selected patients were compared with those of previously reported cases. PATIENTS: Thirty-six previously described patients and 30 additional patients from the current survey, with 41 symptomatic patients and 25 subjectively asymptomatic affected relatives. RESULTS: There were 66 patients with late adult-onset tibial muscular dystrophy. Symptoms appear after the age of 35 years with reduced ankle dorsiflexion, and progress is slow without marked disability. Facial muscles, upper extremities, and proximal muscles are usually spared. Muscle biopsy results reveal nonspecific dystrophic changes in clinically affected muscles, and frequently severe adipose replacement in the anterior tibial muscles occurs. Asymptomatic muscles have mild myopathic changes only. Vacuolar degeneration is detected in a minority of patients. Electromyography shows profound myopathic changes in the anterior tibial muscle, but extensor brevis muscles are well preserved. Computed tomography or magnetic resonance imaging of muscles discloses marked involvement of tibial extensor muscles and focal patches of fatty degeneration in various asymptomatic muscles. Pedigree data suggest autosomal dominant inheritance. CONCLUSIONS: Tibial muscular dystrophy might represent a new form of distal myopathy and it is rather common, at least in Finland. PMID- 8503799 TI - Coping with myasthenia gravis and implications for psychotherapy. AB - The aim of this study was to investigate psychosocial influences and mechanisms of coping to establish indications for psychotherapy in patients with myasthenia gravis. We investigated clinical symptoms, personality, psychopathology, and coping in 44 patients with myasthenia gravis. The patients' personalities were not characteristically altered, and in 29.5% (13/44) of them, preexistent, long term psychiatric disturbances (according to International Classification of Diseases criteria) were present, which corresponds to the prevalence in the average population. In general, coping was characterized by an attitude of calmness and acceptance, which is attributable to effective medical treatment and could be considered an unspecific mode of coping with chronic diseases of moderate severity. Four women had undergone psychotherapy because of neurotic symptoms that were unrelated to myasthenia gravis. At the end of psychotherapy, their myasthenic symptoms had greatly improved or disappeared. Psychotherapeutic techniques may be helpful in patients with neurotic or reactive psychiatric symptoms, but there is no general implication for psychotherapy in myasthenic patients, especially if there is adequate "somatic" therapy. PMID- 8503798 TI - Wallenberg's lateral medullary syndrome. Clinical-magnetic resonance imaging correlations. AB - OBJECTIVE: To correlate clinical and radiologic findings in patients with lateral medullary infarction. DESIGN: Case series with "blinded" evaluation of brain imaging. SETTING: Hospitalized and ambulatory patients at the Neurological Institute of New York (NY). PATIENTS: Thirty-three consecutive patients with lateral medullary syndrome were evaluated by the Stroke Center between 1983 and 1989. RESULTS: Ataxia (70%), numbness either of the ipsilateral face or of the contralateral body (64%), vertigo (51%), and dysphagia (51%) were the most frequent symptoms at onset. Eleven patients had ocular symptoms (diplopia or blurred vision). Horner's syndrome was found in 91%, ipsilateral ataxia in 85%, and contralateral hypalgesia in 85%. Nystagmus (61%) and facial weakness (42%) were less frequent. Head computed tomography was abnormal only when a cerebellar infarction was present (three cases). Magnetic resonance imaging, obtained in 22 cases, was normal in two; a lateral medullary infarction alone was present in 12, and a lesion extending beyond the lateral medulla was found in eight. No correlation was noted between facial weakness or ocular symptoms and infarction extending beyond the lateral medullary region. Vertebral artery disease was confirmed by vascular imaging or insonation studies in 73% of patients. CONCLUSIONS: The triad of Horner's syndrome, ipsilateral ataxia, and contralateral hypalgesia will clinically identify patients with lateral medullary infarction. Facial weakness and ocular symptoms are frequent and do not necessarily imply that the infarction extends beyond the lateral medulla. Cerebellar infarcts only infrequently accompany lateral medullary syndrome, suggesting that most of the posterior inferior cerebellar artery territory is spared, despite the high frequency of vertebral artery occlusion. PMID- 8503800 TI - Abnormal cranial magnetic resonance imaging scans in sickle-cell disease. Neurological correlates and clinical implications. AB - OBJECTIVE: Eight asymptomatic patients with sickle-cell disease (SCD) with magnetic resonance imaging (MRI) abnormalities consistent with cerebral infarcts (group 1) and eight asymptomatic patients with SCD with normal MRI scans (group 2) were followed up to assess the neurological correlates and the clinical outcome. DESIGN: Patients in the two cohorts underwent clinical evaluations and xenon 133 regional cerebral blood flow (rCBF) studies within 1 month of the entry MRI. This study sequence was repeated up to 5 years later. Neuropsychological studies also were performed in six group 1 patients and eight group 2 patients at the end of the study. SETTING: The patients were recruited from the Comprehensive Sickle Cell Center at Columbia University, New York, NY. PATIENTS: All patients had SCD, hemoglobin SS, and normal findings on clinical evaluation at entry. The group 1 cohort had clinically silent MRI abnormalities consistent with cerebral infarction. The group 2 cohort was age matched to group 1 and had normal MRI studies. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The natural history of MRI abnormalities and the neurological correlates were assessed to determine the predictive value of subclinical MRI lesions as a risk factor for clinically apparent stroke. RESULTS: The mean duration of MRI follow-up was 3.7 years. In group 1, four patients (50%) demonstrated progressive MRI abnormalities and three patients (38%) became clinically symptomatic. In group 2, findings for all patients remained normal on clinical and radiological examination. Both groups had markedly elevated rCBF values. Individual rCBF differences correlated with the specific MRI abnormalities. The psychometric study results were similar in the two cohorts. Eighty-three percent of group 1 and 88% of group 2 patients had defective scores in one or more areas of cognitive functioning. Three patients met cognitive criteria for dementia. CONCLUSIONS: Cranial MRI abnormalities have important prognostic implications even when detected in clinically asymptomatic patients. Cognitive abnormalities exist in patients with SCD even in the absence of MRI abnormalities or clinical stroke. PMID- 8503801 TI - The neuropsychology of the prefrontal cortex. AB - Single photon emission computed tomography with the xenon inhalation technique is used to compare activation of regional cerebral blood flow in frontal brain regions during the performance of four widely used neuropsychological tests: the Continuous Performance Test, the Wisconsin Card Sorting Test, the Tower of London, and Porteus Mazes. Healthy normal volunteers performing these tasks show significant increases in frontal regions during the Continuous Performance Test, the Wisconsin Card Sorting Test, and the Tower of London, but not the Porteus Mazes. Activation produced by the Continuous Performance Test and the Tower of London are mesial and bilateral and may reflect stimulation of midline attentional circuits. The Wisconsin Card Sorting Test produces a left dorsolateral area of prefrontal activation. These findings indicate that regional activation of the frontal lobes occurs in response to cognitive challenges produced through performance of standard neuropsychological tests. PMID- 8503802 TI - Time until institutionalization and death in patients with dementia. Role of caregiver training and risk factors. AB - OBJECTIVE: To determine which variables best predict prognosis--time to nursing home admission (NHA) and death--in patients with dementia. DESIGN: Survival analysis employing the Cox proportional hazards model with the use of risk variables pertaining to dementia severity and its rate of progression and caregiver functioning. SETTING: Patients and their caregivers participating in a controlled intervention study of training for caregivers in home management of dementia. PARTICIPANTS: Patients with mild Diagnostic and Statistical Manual of Mental Disorders, Third Edition--defined dementia (N = 91; 68 patients with Alzheimer-type dementia, 20 with vascular dementia, and three with other types) and their caregivers. FOLLOW-UP: All subjects had repeated assessments in the first year to determine rates of change and thereafter annually to determine the date of NHA and/or death. RISK VARIABLES: (1) Caregiver training; (2) dementia severity at index assessment; (3) caregiver stress, neuroticism, and socialization; (4) changes in patients and caregivers during the first 12 months; and (5) patient characteristics. RESULTS: By 5 years' follow-up, 76% of patients had entered a nursing home and 42% had died. Dementia severity and rate of deterioration ("how far" and "how fast") and caregiver psychological morbidity significantly influenced rates of NHA and death. Training of caregivers was significantly associated with delayed NHA and reduced mortality. Greater patient age, non-Alzheimer's dementia, and, unexpectedly, greater caregiver psychological morbidity were associated with shorter survival to death. CONCLUSIONS: Both severity ("how far") and rate of deterioration ("how fast") influence time to NHA and death. Caregiver training may have important ameliorating effects on the prognosis of dementia. PMID- 8503804 TI - The nonenvironmental basis for rising mortality from Parkinson's disease. PMID- 8503803 TI - Environmental causation of Parkinson's disease. PMID- 8503805 TI - Comprehensive evaluation of left hemisphere type I schizencephaly. AB - We report the neuropsychological, magnetic resonance imaging, electroencephalographic telemetry, and sodium amytal test findings of a 32-year old, left-handed man with unilateral left hemisphere type I schizencephaly. The patient was referred for treatment of medically refractory left temporal complex partial seizures that developed at age 26 years. Sodium amytal testing revealed complete incorporation of speech and language function by the right hemisphere. Detailed neuropsychological evaluation indicated average to above-average performance on all measures of language skills, judgment and reasoning, visuospatial abilities, and memory function. This case demonstrates that extensive but lateralized neuronal migration disorders can be associated with complete reorganization and full recovery of function by the contralateral hemisphere. Furthermore, this case supports the view that the degree of recovery is greatest when compensatory mechanisms are activated antenatally. PMID- 8503806 TI - Flight leads and crisis decision-making. AB - Flight leads of fighter aircraft are typically considered to be superior airmen. However, little research has explicitly studied the decision-making ability of flight leads. In this study, the crisis decision-making of pilots in the role of flight lead is examined. Data from 156 fighter aircraft mechanical breakdown mishaps are used to compare the decision-making of flight leads to that of wingmen. The results suggest decision-making performance of flight leads is significantly inferior to wingmen. Further, we demonstrate this effect of flight leadership only affects experienced pilots, not inexperienced pilots. Explanations for this counter-intuitive finding include stress, training practices, and communication limitations. PMID- 8503807 TI - Phenytoin as a countermeasure for motion sickness in NASA maritime operations. AB - Seasickness is the most prevalent form of motion sickness and is an operational problem during Space Shuttle Solid-fueled Rocket Booster (SRB) retrieval. Phenytoin has been shown to protect against motion sickness induced by Coriolis stress. We exposed SRB recovery personnel to off-vertical rotation and sea motion after phenytoin or placebo. Phenytoin blood levels of at least 9 micrograms/ml were protective against motion sickness at sea. No change in susceptibility to nitrogen narcosis was seen in divers in chamber tests at 460 KPa. Phenytoin was used during performance of critical and hazardous tasks during training and actual SRB recovery operations. Phenytoin is an effective operational countermeasure for motion sickness for selected SRB crewmembers. PMID- 8503808 TI - Motion sickness, vascular changes accompanying pseudo-coriolis-induced nausea. AB - We have previously shown that objective measurements of blood flow changes constitute a useful index in assessing susceptibility to nausea produced by cross coupled angular accelerations (Coriolis stimulation). The findings of this study confirm the value of using the same technique for assessing the degree of nausea produced by pseudo-Coriolis effects. PMID- 8503809 TI - Evaluation of zolpidem on alertness and psychomotor abilities among aviation ground personnel and pilots. AB - The use of hypnotics to optimize rest periods during sustained operations could be of help to military personnel. Zolpidem, an imidazopyridine hypnotic, was evaluated for its residual effects on daytime wakefulness in 12 subjects belonging to ground air force personnel and 12 navy fighter pilots. In this controlled double blind crossover study, each subject randomly received zolpidem 10 mg, flunitrazepam 1 mg or placebo, in three separate sessions, 1 week apart at 10 p.m. or 1 a.m., respectively. The absence of residual effects after zolpidem intake was attested by subjective assessments, psychomotor tests (including a simulated flight), and EEG analysis showed that this hypnotic could be considered for operational use. PMID- 8503810 TI - Space and cognition: the measurement of behavioral functions during a 6-day space mission. AB - We measured nonspecific (attention, mental flexibility, psychomotor speed) and visuospatial cognitive processing in a single case study during a 6-d visit on the Russian orbital complex MIR, using computer-based psychometric tasks. Reaction times and accuracy scores showed only minor, nonsignificant changes between preflight, flight, and postflight assessments. These results suggest that several behavioral functions, among them complex visuospatial processing skills, remain essentially intact on short space visits, provided that the performing subject experiences no symptoms of space motion sickness or other physical impairments. Computerized psychometric tasks are a sensitive and flexible tool to measure behavioral functions in space life sciences. PMID- 8503811 TI - Higher capillary filtration rate in the calves of endurance-trained subjects during orthostatic stress. AB - The effect of endurance training on the rate of transcapillary filtration during orthostasis was studied in the human calf. Two groups of sports students with markedly different aerobic capacities performed an orthostatic tilt table test (25 min supine, 10 min upright, 10 min supine). The following parameters were measured: heart rate, brachial and peripheral blood pressure (Finapres), calf volume changes (impedance), and calf blood flow (venous-occlusion-technique). The two groups did not differ in maximal calf circumference, body height, or weight. No syncope occurred, and heart rate and blood pressure responses to upright tilt were similar in both groups. However, the capillary filtration rate revealed much higher values in the trained group: 0.086 vs. 0.036 ml.min-1.100 ml-1. The estimated additional fluid accumulation in the interstitial space in trained subjects may be as high as 260 ml within the first 20 min of orthostasis and may play a role in often reported late syncopes, depending on the preexisting fluid state. PMID- 8503812 TI - Central and peripheral norepinephrine turnover after hindlimb suspension in the rat. AB - After a 9-d hindlimb suspension, the turnover rate of norepinephrine (NE) in rats was determined in A1, A2 (rostral and caudal), A5 and A6 cell groups, as well as in peripheral target organs (heart and kidneys). The NE turnover rate decreased after hindlimb suspension respectively in caudal A2 (67.5%, p < 0.001), rostral A2 (63%, p < 0.001) and in A5 cell groups (62.5%, p < 0.001), but remained unchanged in A1 and A6 regions. The peripheral sympathetic outflow response was selectively modified: in suspended rats, the NE turnover was mainly decreased in atria (79%, p < 0.001) and in ventricles (44%, p < 0.001); there were no biochemical changes in kidneys. It was concluded that a 9-d hindlimb suspension: 1) impaired the noradrenergic neuron activity of A2 and A5 cell groups, which are involved in the central cardiovascular regulation, and particularly in the baroreceptor reflex mechanism; and 2) mainly altered the cardiac NE turnover and induced a selective response of peripheral target organs. PMID- 8503813 TI - Mishap trends and cause factors in naval aviation: a review of Naval Safety Center data, 1986-90. AB - Although the mishap rate in naval aviation has declined substantially over the period from 1950-90, there remains a residual number of mishaps per 100,000 flight hours. Many of these mishaps represent human error. There seems to be an additional risk in certain air-frames and in specific missions. We reviewed mishap trends and causes for all naval aircraft over a 4-year period, 1986-90. These were graphically represented and compared, both statistically and with other methods. The mishap rates contained a significant portion of aircrew error mishaps. Of 308 total Class A mishaps, 179 (58%) were attributed to air-crew error. There were 145 (47%) attributed to supervisory error, another form of human mistakes. Thus, the most common cause factors were directly related to human failure. The effect on training is already being seen with the establishment of air-crew coordination training as one of the top priorities in the Fleet Replacement Squadrons. Studies, both underway and in press, appear to indicate a positive response to this training. PMID- 8503814 TI - Perfusion of the visual cortex during pressure breathing at different high-G stress profiles. AB - The effects of pressure breathing for G protection (PBG) on perfusion of the visual cortex were studied in a subject during various high-G stress profiles. Blood flow velocity was measured in the posterior cerebral artery using a transcranial Doppler (TCD) ultrasound instrument. The G profiles examined included gradual and rapid onset rates. Mean cerebral blood flow velocity (MCBFV) declined with increasing +Gz with G-suit protection alone. The MCBFV increased in direct proportion with increase in +Gz acceleration with PBG. The mediating mechanisms for the effects of PBG may include improved gaseous exchange, the diminished sympathicoadrenal discharges, and cardiopulmonary reflexes. A role for TCD in further research is indicated. PMID- 8503815 TI - A simple hindlimb suspension apparatus. AB - This paper describes the assembly of a simple, inexpensive apparatus for application of the hindlimb suspension model to studies of the effects of unloading on mammalian physiology. Construction of a cage and suspension assembly is described using materials that can be obtained from most hardware stores. The design is kept simple for easy assembly and disassembly to facilitate cleaning and storage. The suspension assembly allows the animals full access to all portions of the floor area and provides an effective environment to study the effects of unloading. PMID- 8503816 TI - For want of a flight surgeon.... AB - In 1863, Captain John Randolph Bryan conducted the Confederate States Army's first military reconnaissance balloon flights. On his second flight, he survived a class "A" aviation mishap. This article discusses the probable contributing mishap factors stemming from the lack of an effective aviation medicine program with appropriate flight surgeon input and participation. Physical standards, flying duty medical examinations, the Acceptability Rating for Military Aeronautics (ARMA), crew rest regulations, unit safety programs, physiological training, aviation life support equipment (ALSE), night vision training, survival training, and aircraft accident investigation are explored. PMID- 8503818 TI - Disorientation. PMID- 8503817 TI - Photo-refractive keratectomy (PRK): threat or millennium for military pilots? AB - The development of the excimer laser, which is capable of correcting myopia without leaving obvious scars as does radial keratotomy, makes it certain that this promising but very new modality is something the military aviation community will be facing in the immediate future. Methods of detection are available, but are expensive and time-consuming. Should military aviation permit or even sponsor a group of PRK student pilots in order to observe them closely, and then perhaps use this new modality in place of contact lenses or even spectacles? PMID- 8503819 TI - You're the flight surgeon. Thoracic leiomyoma. PMID- 8503820 TI - Aircraft accident investigation. PMID- 8503821 TI - Psychiatrists/clinical psychologists at sea. PMID- 8503822 TI - A study of behavioral and sensorial bases of radial maze learning in mice. AB - In order to analyze the various sensorial and behavioral modes implied in learning on a radial maze, three isogenic mice groups (BALB/C, C57BL/6, and CB6F1) were subjected to four different learning procedures, each ending with a probe test. These four procedures examined the use of radial strategies and allowed to dissociate the use of olfactory and spatial cues. Results showed that all mice preferred to use a radial strategy. When the confinement procedure rendered the use of a radial strategy impossible, BALB/C mice were incapable of establishing spatial orientation but were able to learn the task by using olfactory cues. C57BL/6 mice, on the other hand, seemed to use spatial cues exclusively, while the CB6F1 hybrids showed a high degree of plasticity, using either type of information. These strain-specific differences point out the heterogeneity of the processes called into play during radial maze learning and show that unless olfactory cues are carefully controlled they can account for choice accuracy in some mice. PMID- 8503823 TI - A dissociation between the proactive ECS effects on inhibitory avoidance learning and on classical fear conditioning. AB - This study investigated if the nature of the task is a determinant factor of whether or not a series of electroconvulsive shock (ECS) will proactively affect learning in animals. Rats were administered one daily ECS for 7 days. A day after the last administration they were concomitantly trained on an inhibitory avoidance task and on classical conditioning of fear response to a brief tone. Twenty-four hours later they were exposed for 8 min to an open-field arena and the freezing reaction was measured both before and after tone presentation (classical fear conditioning test). On the subsequent day the step-through latency (without presentation of the tone) was measured on the avoidance apparatus (inhibitory avoidance test). Impairment of inhibitory avoidance was seen in ECS-administered animals in comparison to controls, but the freezing reaction to the tone was equally high in both groups. Additional groups of rats were trained in order to control for ECS alone-induced freezing and pseudoconditioning. Also, it was demonstrated that the differential ECS effects on the two tasks were not due to the order of testing since similar dissociation was obtained when inhibitory avoidance test was conducted before the open-field test. PMID- 8503824 TI - S-adenosyl-L-methionine decreases motor activity in the rat: similarity to Parkinson's disease-like symptoms. AB - S-Adenosyl-L-methionine has been shown to cause Parkinson's disease-like effects that include hypokinesia, tremor, rigidity, and abnormal posture. S-Adenosyl-L methionine is the rate-limiting endogenous methyl donor. Its biochemical role, which includes the metabolism of dopamine and the synthesis of acetylcholine, also resembles the changes that occur in Parkinson's disease. Therefore, S adenosyl-L-methionine may play a role in Parkinson's disease-like motor impairments. In this study we manipulated the levels of S-adenosyl-L-methionine in the brain of rats and quantified the changes in hypokinetic type motor activity that seems to occur also in Parkinsonism. Male Sprague-Dawley rats were anesthetized with chloral hydrate (400 mg/kg/rat), cannulated, injected into the lateral ventricle with S-adenosyl-L-methionine or saline, and their motor activity was measured in a Digiscan Animal Activity Monitor. Other behaviors were also observed. S-Adenosyl-L-methionine caused hypokinesia, tremor, rigidity, and abnormal posture in rats. Motor activity was significantly decreased within 2 min postinjection. The hypokinesia was maximal at 60 min, at which time a 65, 75, and 90% decrease for total distance, number of movements, and the ratio of total distance to the number of movements occurred, respectively. The hypokinetic effect of S-adenosyl-L-methionine was dose dependent. A 65.0 and 51.3% decrease in total distance and number of movements, respectively, were observed following 9.38 x 10(-9) mol. The 5.0 x 10(-8) mol caused a reduction of 73.42 and 57.66% and 4.0 x 10(-7) mol/rat caused a 94.9 and 78.43% decrease, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8503825 TI - 5,7-Dihydroxytryptamine lesions in the fornix-fimbria attenuate latent inhibition. AB - When animals are preexposed to a stimulus without consequence they are subsequently slower to associate this stimulus with an important event, such as footshock. This retarding effect of stimulus preexposure is called latent inhibition and can be demonstrated in a variety of classical and instrumental paradigms and in a wide range of species, including man. Latent inhibition is disrupted in acute schizophrenics and by amphetamine treatment in both rat and man. The present study investigated the role of hippocampal 5HT terminals in latent inhibition using a conditioned suppression procedure with male Sprague Dawley rats. Microinjections of 5,7-dihydroxytryptamine in the fornix-fimbria significantly reduced hippocampal indoleamine levels and attenuated latent inhibition of conditioned suppression. This finding supports the hypothesis that the destruction of mesolimbic 5-hydroxytryptamine terminals reduces latent inhibition. This result is discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder. In addition to the predicted lesion effect, biochemical analyses indicated that experimental treatments in the latent inhibition procedure altered neurotransmitter turnover: utilization ratios for 5-hydroxytryptamine and/or dopamine were increased in preexposed relative to nonpreexposed animals in four of the six brain regions sampled. PMID- 8503826 TI - A lower bound on the detectability of nonassociative learning in the local bending reflex of the medicinal leech. AB - Studies of neural mechanisms of learning and memory have focused on large changes at identified synapses. However, memory in distributed processing reflexes could involve widely distributed engrams characterized by small changes at every synapse in the network. To investigate this possibility, we used a neural network optimization algorithm to construct distributed engrams for nonassociative conditioning in a model of the local bending reflex of the medicinal leech (Hirudo medicinalis). The model comprised 4 sensory neurons, 10 to 40 interneurons, 8 motor neurons, and up to 480 connections. Synaptic connections in the model were first optimized to reproduce the amplitude and time course of motor neuron synaptic potentials recorded during local bending. This network, which represented the naive state before conditioning, was then reoptimized to the habituated or sensitized state. Following reoptimization, the memory for nonassociative learning was encoded by small changes dispersed across the entire network, and each change made only a small contribution to the learning. Moreover, because the changes were small, resolution of a few tenths of a millivolt, or 3-5% of an average synaptic potential, would be needed to account for half of the nonassociative learning. These results show how difficult distributed engrams can be to detect and provide a likely lower bound on the detectability of nonassociative learning in this and related networks. PMID- 8503827 TI - Frequent reward eliminates differences in activity between hyperkinetic rats and controls. AB - The spontaneously hypertensive rat (SHR) is a strain that is a potential animal model of attention-deficit hyperactivity disorder (ADHD)/childhood hyperkinesis/disturbance of activity and attention, as SHR exhibit both hyperactivity and attention problems. Altered reinforcement (reward) processes have been suggested as the mechanism for the development of hyperactivity in SHR and ADHD. The purpose of the present study was to analyze basic reinforcement and response processes in the hyperactive SHR and in the progenitor Wistar-Kyoto (WKY) control strain. The results show that differences between the strains emerge in response rates maintained by infrequent reinforcers rather than in asymptotic rates of responding maintained by higher rates of reinforcement. The SHR strain required fewer reinforcers per minute to maintain high rates of responding, but when reinforcer rates were high enough to maintain asymptotic response rates in both strains, the rates were similar. Thus, the increased response rates for hyperactive rats at low reinforcement rates may reflect not only barpresses for water, but possibly also barpresses for other stimuli the animal produces by pressing the lever switch. Extrapolating to hyperactive children (ADHD), the results suggest that ADHD behavior might be made more similar to non-ADHD if reinforcers were scheduled more frequently. PMID- 8503828 TI - Genetic analysis of isolation-induced aggression in the mouse. III. Classical cross-breeding analysis of differences between two closely related inbred strains. AB - In two preceding papers we reported on two closely related inbred mouse strains, ABG and AB@Halle that display very large differences in isolation-induced intermale aggression. In the present article we investigated animals from a complete Mendelian cross between these strains to test the hypothesis that the behavioral difference is due to genetic variation at only a few loci, possibly only one. In the quantitative-genetic analysis of generation means and variances for the behavioral variables analyzed, relatively simple models were found. As epistasis was present in some cases, the monogenic hypothesis could not be confirmed. Also, the analysis of the segregating generations by means of Collins' nonparametric method revealed significant deviations of observed from expected distributions. We conclude that differences at more than only one single locus are correlated with the behavioral difference. PMID- 8503829 TI - Disruption of species-specific behavior in neonatal quail following chronic prenatal ethanol exposure. AB - Bobwhite quail embryos were exposed to ethanol (5 mg every other day) from E5 to E21. Control embryos received comparable saline injections or were untreated. At 24 h posthatch, the neonates were tested in a single call approach test, using a Bobwhite maternal exodus call which had previously been shown to be a potent attractant to these animals. Almost all animals in all three groups approached the call, and latency of approach did not differ among the groups. The ethanol treated animals, however, spent significantly less time within the approach area and exited the area significantly more often than did either the saline or untreated controls. Overall hyperactivity or loss of auditory acuity did not appear to account for the response deficits. These results suggest that species specific behaviors might be a useful paradigm for the study of fetal alcohol effects. PMID- 8503830 TI - Spatial learning in an enclosed eight-arm radial maze in rats with sodium arsanilate-induced labyrinthectomies. AB - Bilateral vestibular dysfunction was induced in Long-Evans male rats (n = 7) by intratympanic injections of sodium arsanilate (30 mg/side). Control rats (n = 6) received isotonic saline. Animals were tested for labyrinthine integrity by measuring air-righting and contact-righting reflexes. Rats were reduced to 85% of free-feeding body weight and tested in an enclosed 8-arm radial maze (1 trial/day over 10 days). Labyrinthectomized animals made significantly more errors (p < .001) and, unlike the controls, showed no significant improvement on this measure over acquisition training. These rats also made significantly more (p = 0.018) sequential same arm reentries and fewer sequential adjacent arm entries (p < .01). These findings demonstrate that information obtained from the vestibular system is very important in spatial learning in the rat. PMID- 8503831 TI - Histochemical detection of glycogen phosphorylase activity as parameter for early ischemic damage in rat heart. AB - In the present study we have investigated whether enzyme histochemical parameters can be applied to detect early ischemic damage in rat heart after ischemia without restoration of the blood flow. Ischemia was induced by incubating heart fragments for 0, 10, 20, 30, 60, 120 and 240 min at 37 degrees C. The activity and localization of the following enzymes was studied in unfixed cryostat sections using quantitative histochemical methods: lactate dehydrogenase, creatine kinase, succinate dehydrogenase, phosphofructokinase, acid phosphatase, 5'-nucleotidase and glycogen phosphorylase. Moreover, the ultrastructure of the tissue was studied with special attention to the appearance of flocculent densities in mitochondria, which can be seen as a sign of irreversible cell damage. It was shown that glycogen phosphorylase activity in rat heart decreased after short periods (30 min) of in vitro ischemia, whereas all other enzymes studied were not decreased up to 240 min, with the exception of lactate dehydrogenase and phosphofructokinase activities which were diminished only at 240 and 120 min of ischemia, respectively. Some reaction product was found after incubating for 5'-nucleotidase activity in the absence of substrate, indicating the presence of endogenous substrate(s). This endogenous substrate disappeared from the myocytes after 20 min of ischemia. It is assumed that AMP and/or other phosphate-containing compounds play an essential role in the activation of glycogen phosphorylase. Significant reduction of glycogen phosphorylase activity is correlated with the irreversible stage of damage of myocytes as judged from the ultrastructure. PMID- 8503832 TI - Interleukin-8 is not involved in the increased chemotactic activity of peripheral blood plasma during acute myocardial infarction. AB - Polymorphonuclear neutrophils (PMN) are known to participate in the development of tissue injury during myocardial infarction due to both free oxygen radicals release, as well as to their involvement in the "no-reflow" phenomenon. We have previously shown that peripheral blood plasma (obtained from patients with acute myocardial infarction) has chemotactic activity for PMN and is able to induce PMN adherence as well as superoxide anion production. To investigate whether interleukin-8 (IL-8/NAP-1), a potent chemotactic factor for PMN, is involved in plasma-mediated PMN stimulation, we measured plasma levels of IL-8 in five patients with transmural myocardial infarction with highly sensitive enzyme linked immunosorbent assay (ELISA) using specific antibodies. Blood samples were taken immediately after patients' admission, within 15 and 30 min of treatment with intravenous nitrates, as well as after 1, 2, 3, and 7 days. All samples expressed IL-8 activity within the detection limit (0.4 ng/ml) as observed at the basal state. Thus, IL-8 may not be considered as responsible for the chemotactic activity in peripheral blood in patients with myocardial infarction. PMID- 8503833 TI - Significance of cardiac innervation on spontaneous ventricular arrhythmias elicited by left stellate ganglion stimulation in dogs 4 days after myocardial infarction: comparison of two experimental models. AB - The effects of cardiac sympathetic overactivity on spontaneous arrhythmias and transmural left ventricular effective refractory period (LVERP) were assessed by left stellate stimulation (LSS) in 16 anesthetized dogs. The experiments were performed 4 days after proximal occlusion of the left anterior descending (LAD) coronary artery produced by either ligation (9 dogs) or embolization with histoacryl (7 dogs). The innervation of left ventricular myocardium was studied by light and electron microscopies. Synaptophysin (SYN)- and neuropeptide Y (NPY) immunoreactive nerve fibers and terminals were thereby detected. In dogs subjected to ligation, LSS elicited negligible arrhythmias in spite of a decrease in LVERP by 6.9 +/- 2.2% (mean +/- SD, p < 0.001). However, dogs with intravascular occlusion were more susceptible to LSS, as indicated by development of sustained ventricular rhythms. In these animals, the LVERP decreased with LSS by 14.6 +/- 3.4% (p < 0.001). The innervation of the anterior left ventricular wall distal to the place of occlusion revealed a higher reduction of SYN- and NPY immunoreactive nerves in infarcted myocardium and a more heterogeneous distribution of nerves in undamaged regions after ligation, compared to intravascular occlusion. Ultrastructurally, nerve terminals containing small agranular and large dense-core vesicles were found innervating ischemically damaged myocardiocytes. Our findings indicate a higher preservation of nerves in infarcted and noninfarcted myocardium of animals subjected to embolic occlusion of the LAD. Because LSS apparently elicited more arrhythmias in these animals, we suggested a proarrhythmic effect of intact myocardial innervation after infarction. PMID- 8503834 TI - Effect of coronary occlusion and reperfusion on local electrical resistivity of myocardium in dogs. AB - The effect of coronary occlusion and reperfusion on myocardial electrical resistivity was studied in nine anesthetized open-chest dogs. Anisotropic resistivity was measured on the anterior free wall of the left ventricle (LV) before (control) and during transient occlusion of the left anterior descending (LAD) coronary artery, and during reperfusion. To measure local resistivity longitudinal (RL) and transverse (RT) to epicardial muscle fiber direction, a sensor was developed based on the four electrode (FE) technique with an electrode distance of 1 mm. Previous calculations showed that measurements with this system were confined to a 2-mm-thick epicardial layer. Control values for RL and RT were 243 +/- 32 ohms.cm and 358 +/- 45 ohms.cm (mean +/- SD, n = 9) respectively. During a 2-min LAD occlusion, RL increased gradually by 12.4% (p < 0.05) and RT by 7.8% (p < 0.05) above the preceding control values. During a 5-min reperfusion period resistivities returned towards control values, but tended to remain elevated. RL showed a slight initial further increase during the first min of reperfusion and remained significantly above control values during 3 min of reperfusion. RT returned to values not significantly different from control after about 1 min of reperfusion. PMID- 8503835 TI - Regulation of an hepatic low-M(r) membrane-associated protein-tyrosine phosphatase. AB - Protein-tyrosine phosphatases (PTPases), active against autophosphorylated insulin and epidermal growth factor (EGF) receptors in rat liver, are predominantly membrane associated. Fasting of rats for 48 h decreased hepatic particulate PTPase activity by 15.0-26.9%. This reduction in particulate PTPase activity was due to a rather specific decrease in activity of > 85% of a single species of PTPase, termed PTPase I. Disappearance of PTPase I activity from the particulate fraction was not accounted for by its translocation to the cytosol. PTPase I displayed the highest activity against autophosphorylated insulin and EGF receptors, relative to activity against a 32P-labelled peptide substrate, of three PTPases resolved from the liver particulate fraction. The M(r) value of PTPase I, as determined by gel filtration on a Superose 12 column was approx. 42,000, indicating that PTPase I belongs to the low-M(r) class of PTPases. An antibody raised against PTPase 1B, the prototype of this class of PTPases, did not react with PTPase I in Western blots. The potential importance of the novel change in activity of PTPase I in the regulation of insulin-receptor signal transduction is discussed. PMID- 8503837 TI - Changes in lipoprotein lipase activities in adipose tissue, heart and skeletal muscle during continuous or interrupted feeding. AB - Lipoprotein lipase (LPL) activities in parametrial and interscapular adipose tissue, soleus and adductor longus muscles and hearts of female rats were measured during progressive starvation, chow re-feeding after 24 h starvation and throughout dark and light phases in rats permitted unrestricted access to chow. Adipose-tissue LPL activities declined by 50% after 6 h starvation and continued to fall as the starvation period was extended to 24 h. Skeletal-muscle LPL activities dramatically increased between 9 and 12 h of starvation. Cardiac LPL activities increased 2.5-fold within 6 h of starvation, reaching a maximum after 12 h of starvation. Adipose-tissue LPL activities increased rapidly within 2 h of re-feeding chow ad libitum after 24 h starvation, achieving 'fed ad libitum' values after 6 h. Oxidative-skeletal-muscle LPL activities also increased after 2 h of refeeding and exceeded 'fed ad libitum' values throughout the 6 h re-feeding period. Cardiac LPL activities remained up-regulated for the 6 h of re-feeding. Adipose-tissue LPL activities exceeded those of cardiac or skeletal muscle throughout both light and dark phases. The lowest adipose-tissue LPL activities were observed at 9 h into the light phase. In contrast, cardiac LPL activity declined throughout the dark phase, with a minimum at 9 h into the dark phase. No such variation was observed for skeletal-muscle LPL activities. A diurnal nadir in plasma triacylglycerol (TG) concentrations coincided with the peak in cardiac LPL activities. The results demonstrate that, during unrestricted feeding and re feeding after prolonged starvation, changes in skeletal-muscle and adipose-tissue LPL activities are neither reciprocal nor co-ordinate. Regulation of cardiac LPL activity during the diurnal cycle may be an important aspect of both of cardiac fuel selection and whole-body TG metabolism. PMID- 8503836 TI - Post-transcriptional regulation of apolipoprotein E expression in mouse macrophages by phorbol ester. AB - Phorbol ester-mediated differentiation of THP-1 cells (a human monocytic cell line) into mature macrophages is associated with a transcriptional induction of apolipoprotein E (apoE) expression [Auwerx, Deeb, Brunzell, Peng and Chait (1988) Biochemistry 27, 2651-2655]. Endotoxin, on the other hand, which may also act through activation of protein kinase C, is a potent inhibitor of apoE expression in mouse macrophages [Werb and Chin (1983) J. Biol. Chem. 258, 10642-10648]. The present experiments examine the effect of phorbol ester, an activator of protein kinase C, on the apoE expression in mouse thioglycollate-elicited peritoneal macrophages. Phorbol ester inhibits apoE expression in a specific, time- and dose dependent manner. A 75% inhibition in the rate of apoE secretion, but not that of total protein, was observed following a 4.5 h incubation with 160 nM phorbol ester, although nearly full inhibition was obtained with 40 nM. The changes in apoE secretion were paralleled by similar changes in apoE synthesis, indicating synthesis as the primary site of action. The decreased rates of apoE synthesis are shown not to be due to increased apoE degradation. The profound inhibition of apoE synthesis was not accompanied by significant changes in apoE mRNA levels at any concentration of phorbol ester (up to 16 microM), or length of treatment (up to 24 h), suggesting a post-transcriptional locus of regulation of apoE expression. Although the early changes in apoE synthesis correlate with increased microsomal protein kinase C activity, the suppression of apoE expression persists even during conditions of nearly complete (> 95%) loss of protein kinase C activity, suggesting that the direct or indirect effect of protein kinase C on apoE expression is mediated by a stable phosphorylated protein, or that the observed effects are mediated through a protein kinase C species that is not readily downregulated by phorbol esters. The presented studies clearly demonstrate the potential importance of the translational regulation of apoE expression through the protein kinase C signal transduction pathway. PMID- 8503838 TI - Phospholipase D activity in phagocytic leucocytes is synergistically regulated by G-protein- and tyrosine kinase-based mechanisms. AB - The regulation of phospholipase D (PLD)-type effector enzymes by G-proteins and protein kinases/phosphatases was characterized in the U937 human promonocytic leucocyte line. PLD activity was assayed by measuring (in the presence of 1% ethanol) the accumulation of phosphatidylethanol in cells permeabilized with beta escin, a saponin-like detergent. Basal PLD activity was very low when cells were permeabilized and incubated in cytosol-like medium containing micromolar [Ca2+]. When this medium was supplemented with exogenous MgATP or guanosine 5'-[gamma thio]triphosphate (GTP[S]), PLD activity increased by 9- and 14-fold respectively. Cells permeabilized in the absence of exogenously added MgATP, but in the presence of 1 microM vanadate/100 microM H2O2, also exhibited a modest 12 fold increase in PLD activity. However, the simultaneous presence of either GTP[S] plus exogenous MgATP or GTP[S] plus vanadate/H2O2 (and endogenous MgATP) induced similar 60-75-fold increases in the rate and extent of phosphatidylethanol accumulation. These latter effects of vanadate/H2O2 were strongly correlated with the very rapid accumulation of multiple tyrosine phosphorylated proteins. Other studies utilized cells which were permeabilized in the presence of GTP[S] and then washed before assay of PLD. These cells retained approximately 60% of the MgATP-regulatable PLD activity (EC50 approximately = to 100 microM MgATP) observed in freshly permeabilized non-washed cells. In the absence of GTP[S] pre-treatment, washed cells retained minimal PLD activity. Genistein, a tyrosine kinase inhibitor, significantly attenuated the ability of MgATP to stimulate PLD activity and accumulation of tyrosine-phosphorylated proteins in the washed GTP[S]-treated cells. These data suggest that PLD activity in myeloid leucocytes involves co-ordinate regulation by both G-protein(s) and tyrosine phosphorylation. PMID- 8503839 TI - Differential modulation of degradative and repair responses of interleukin-1 treated chondrocytes by platelet-derived growth factor. AB - Interleukin 1 (IL-1) plays a dual role in cartilage matrix degeneration by promoting extracellular proteinase action such as the matrix metalloproteinases (increased degradation) and by suppressing the synthesis of extracellular matrix molecules (inhibition of repair). Platelet-derived growth factor (PDGF) is a wound-healing hormone which is released along with IL-1 during the inflammatory response. Since previous studies have shown that PDGF enhances IL-1 alpha effects on metalloproteinase activity, in this report, we have examined whether PDGF modifies IL-1 beta effects on cartilage proteoglycan synthesis. Initially, we confirmed that rabbit articular chondrocytes treated with IL-1 beta + PDGF induced higher proteinase activity, in comparison with IL-1-treated cells. We further observed that the increased proteinase activity correlated with an increase in the synthesis of collagenase/stromelysin proteins and a corresponding increase in the steady-state mRNA levels for both the enzymes. Studies on IL-1 receptor expression suggested that PDGF caused an increase in IL-1 receptor expression which, by augmenting the IL-1 response, may have led to the increase in proteinase induction. Analysis of proteoglycan synthesis confirmed that IL-1 reduced the incorporation of sulphated proteoglycan, aggrecan, into the extracellular matrix of chondrocytes, whereas PDGF stimulated it. However, cells treated with IL-1 + PDGF synthesized normal levels of aggrecan. This is in contrast with cells treated with IL-1 + fibroblast growth factor, in which case only proteinase activity was potentiated. The results allow us to conclude that (a) the two effector functions that play a role in matrix remodelling, namely matrix lysis (proteinase induction) and matrix repair (proteoglycan synthesis), occur via distinct pathways and (b) PDGF may play a crucial role in cartilage repair by initially causing matrix degradation followed by promoting new matrix synthesis. PMID- 8503840 TI - A novel aldehyde reductase with activity towards a metabolite of aflatoxin B1 is expressed in rat liver during carcinogenesis and following the administration of an anti-oxidant. AB - In contrast with fractions from control animals, an aldehyde reductase, which catalyses the reduction of aflatoxin B1-dihydrodiol, in the dialdehyde form at physiological pH values, to aflatoxin B1-dialcohol, is expressed in cytosolic fractions prepared from rat livers bearing pre-neoplastic lesions, or following treatment with the anti-oxidant ethoxyquin. This expression parallels the development of resistance to the toxin. Unlike the aflatoxin B1-dihydrodiol, the dialcohol does not undergo binding to protein. This enzyme activity could play a mechanistic role in hepatocarcinogenesis and chemoprotection in the rat. Correlated n.m.r. and m.s. spectra are provided in Supplementary Publication SUP 50171 (3 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1993) 289, 9. PMID- 8503841 TI - Corticosteroidogenesis in the toad Bufo arenarum H: evidence for a precursor role for an aldosterone 3 beta-hydroxy-5-ene analogue (3 beta, 11 beta, 21-trihydroxy 20-oxo-5-pregnen-18-al). AB - A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18 hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor. PMID- 8503842 TI - Determinants of oligomeric structure in the chicken liver glycoprotein receptor. AB - The oligomeric state of the chicken liver receptor (chicken hepatic lectin), which mediates endocytosis of glycoproteins terminating with N-acetylglucosamine, has been investigated using physical methods as well as chemical cross-linking. Receptor isolated from liver and from transfected rat fibroblasts expressing the full-length polypeptide is a homotrimer immediately following solubilization in non-ionic detergent, but forms the previously observed hexamer during purification. These results are most consistent with the presence of a trimer of receptor polypeptides in liver membranes and in transfected cells. Analysis of truncated receptors reveals that the C-terminal extracellular portion of this type-II transmembrane protein does not form stable oligomers when isolated from the membrane anchor and cytoplasmic tail. The behaviour of chimeric receptors, in which the cytoplasmic tail of the glycoprotein receptor is replaced with the corresponding segments of rat liver asialoglycoprotein receptor or the beta subunit of Na+,K(+)-ATPase, or with unrelated sequences from globin, indicates that the cytoplasmic tail influences oligomer stability. Replacement of N terminal portions of the receptor with corresponding segments of influenza virus neuraminidase results in formation of tetramers, suggesting that the membrane anchor and flanking sequences are important determinants of oligomer formation. PMID- 8503843 TI - Isolation of a glycoprotein responsible for the enhanced concanavalin A agglutinability of erythrocytes in Yoshida-ascites-sarcoma-bearing rats: the mechanism of paraneoplastic syndromes. AB - As a model for the development of paraneoplastic syndromes, we have studied the mechanism by which erythrocytes in the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma acquire higher agglutinability with concanavalin A (Con A). The in vitro incubation of erythrocytes from normal animals with the cell-free ascites fluid or the plasma of tumour-bearing animals is able to confer an enhanced agglutinability on the cells. Fractionation of the ascites fluid has yielded three subfractions that are active in vitro. Two of these, occurring in small amounts, are a particulate fraction rich in plasma membrane markers and a soluble fraction containing protein of molecular mass equal to or less than 50 kDa. These two are, however, unable to affect the agglutinability of erythrocytes in vivo, i.e. when injected intraperitoneally into normal rats. The third, and major, fraction consists of proteins of molecular mass equal to or greater than 680 kDa, and is able to modify the erythrocyte agglutinability in vivo. From this fraction, by using a combination of Con A affinity chromatography, gel filtration, (NH4)2SO4 fractionation and DEAE-Sephadex chromatography, an active protein has been purified to apparent homogeneity. It yields a subunit of 310 kDa in the presence of SDS and further breaks down into a polypeptide of 170 kDa when reduced with 2-mercaptoethanol. It has a pI of 5.35. The protein is rich in Glx, and appears to contain hybrid-type N-linked oligosaccharides. The protein is also present in the blood plasma of tumour-bearing, but not normal, rats. The radioiodinated protein binds to the erythrocyte surface adding about 7400 molecules/cell. The study unequivocally demonstrates that a protein from the tumour fluid can appear in the circulation, interact with host cells that are not in contact with the tumour and modify their properties. PMID- 8503844 TI - Organic anions exhibit distinct inhibition patterns on the low-Km and high-Km transport of S-(2,4-dinitrophenyl)glutathione through the human erythrocyte membrane. AB - The low-Km and high-Km components of S-dinitrophenyl-glutathione (DNPSG) uptake by inside-out vesicles of human erythrocytes show different pH profiles and inhibition properties with organic anions. Both components are competitively inhibited by various polyvalent anions, including glutathione conjugates, conjugated steroid hormones and bile salts, and bilirubin ditaurate. A variety of monovalent anions, including glucuronidated and sulphated drugs and taurocholate, inhibit the high-Km system only. Taurocholate is taken up by the erythrocyte vesicles in an ATP-dependent manner. The anionic dyes fluorescein, Indocyanine Green and bromosulphophthalein inhibit the low-Km system competitively and the high-Km system non-competitively. The study shows that interactions between different types of biologically occurring conjugates can occur at the level of the transport step out of erythrocytes. The kinetic properties suggest overlapping substrate specificities for the two systems, in which the low-Km component is physiologically more important for transport of glutathione conjugates and polyvalent organic anions, whereas the high-Km component is of significance for transport of monovalent organic anions. Low- and high-Km transport of DNPSG is also observed in plasma membrane vesicles from rat, pig and bovine erythrocytes. PMID- 8503845 TI - Up-regulation of the amount of Gi alpha 2 associated with the plasma membrane in human neutrophils stimulated by granulocyte-macrophage colony-stimulating factor. AB - Preincubation of human neutrophils with the human cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) results in an increase in the amount of alpha subunit of Gi2 (Gi alpha 2) associated with the plasma membrane and a corresponding decrease in the amount associated with the granule fractions. Similar results are obtained with interleukin-8. GM-CSF has no effect on the distribution of Gi alpha 3. The effect of GM-CSF on Gi alpha 2 is time-dependent, and, although a significant effect can be observed after incubation for 5 min with GM-CSF, the enhancement increases with increasing time. Genistein, a protein tyrosine kinase inhibitor, and 1,2-bis-(O-aminophenoxyl)ethane-NNN'N'-tetra acetic acid (BAPTA), an intracellular Ca2+ chelator, decrease the stimulatory effect of GM-CSF. On the other hand, the protein-synthesis inhibitor cycloheximide does not affect the action of GM-CSF. Also, although preincubation of human neutrophils with GM-CSF increases the levels of Gi alpha 2 in the plasma membrane it does not alter the total amount of cellular Gi alpha 2. In addition, the level of Gi alpha 2 mRNA, unlike that of the proto-oncogene c-fos, is not increased in cells treated with GM-CSF. This indicates that the observed increase in the amount of Gi alpha 2 associated with the plasma membrane is not due to the synthesis of new Gi alpha 2. These data provide insight into the mechanism by which GM-CSF may prime human neutrophils for increased responsiveness to subsequent stimulation by G-protein-dependent agonists. PMID- 8503846 TI - Cloning and characterization of the major hepatic glutathione S-transferase from a marine teleost flatfish, the plaice (Pleuronectes platessa), with structural similarities to plant, insect and mammalian Theta class isoenzymes. AB - A cDNA clone (PLGSTA) of 896 bp, containing an open reading frame encoding a 225 amino-acid polypeptide of M(r) 25,723, was isolated from a cDNA library constructed in lambda gt11 from the liver of a marine teleost flatfish, the plaice (Pleuronectes platessa). The identification of this cDNA as that coding for the subunit of the major cytosolic glutathione S-transferase of plaice liver, GST-A, was supported by its heterologous expression in and purification of its protein product from Escherichia coli. The recombinant-derived protein exhibited identical M(r) and immunoreactivity and a similar substrate specificity to GST-A previously isolated from plaice liver. Comparison of the deduced amino acid sequence of the plaice GST-A polypeptide with the primary structures of GSTs from other Phyla revealed that it showed the greatest similarity to plant, insect and mammalian Theta class GSTs. Southern blot analysis of plaice DNA hybridized to the PLGSTA cDNA showed a banding pattern indicative of the presence of a single gene. Northern blot analysis of a variety of plaice tissues showed hybridizing bands of approx. 1100 nucleotides in all tissues tested, with the highest relative amounts in liver and intestinal mucosa. A marked increase in hybridization intensity was observed in hepatic RNA samples from plaice treated with trans-stilbene oxide, suggesting that GST-A is induced by epoxides in this species. PMID- 8503847 TI - Production, purification and characterization of the catalytic domain of glucoamylase from Aspergillus niger. AB - The catalytic domain of glucoamylases G1 and G2 from Aspergillus niger is produced in vitro in high yield by limited proteolysis using either subtilisin Novo or subtilisin Carlsberg. Purification by affinity chromatography on an acarbose-Sepharose column followed by ion-exchange chromatography on HiLoad Q Sepharose leads to separation of a number of structurally closely related forms of domain. The cleavage occurs primarily between Val-470 and Ala-471 as indicated by C-terminal sequencing, whereas the N-terminus is intact. Subtilisin Carlsberg, in addition, produces a type of domain which is hydrolysed before Ser-444, an O glycosylated residue. This leaves the fragment Ser-444-Val-470 disulphide-bonded to the large N-terminal part of the catalytic domain. Subtilisin Novo, in contrast, tends to yield a minor fraction of forms extending approx. 30-40 amino acid residues beyond Val-470. The thermostability is essentially the same for the single-chain catalytic domain and the original glucoamylases G1 and G2, whereas the catalytic domain cut between Ser-443 and Ser-444 is less thermostable. For both types of domain the kinetic parameters, Km and kcat., for hydrolysis of maltose are very close to the values found for glucoamylases G1 and G2. PMID- 8503848 TI - Stimulation of platelet-activating factor synthesis by progesterone and A23187 in human spermatozoa. AB - The presence of platelet-activating factor (PAF) has been demonstrated recently in mammalian spermatozoa, together with evidence for a role of this phospholipid in enhancing sperm motility and fertilizing ability. To investigate whether PAF synthesis and release occurs in human spermatozoa following incubation with stimuli that induce acrosome reaction, spermatozoa were incubated with progesterone and A23187, two known inducers of the exocytotic event. PAF synthesis (remodelling pathway) was assessed by [3H]acetate incorporation into PAF. Treatment of spermatozoa with progesterone and A23187 resulted in an increase of [3H]acetate incorporation into PAF. Most of the newly synthesized [3H]PAF formed in response to acrosome reaction was found in the supernatant, suggesting a release of the phospholipid from spermatozoa. PAF-like material extracted from human spermatozoa was able to induce aggregation of rabbit platelets and showed identical retention time and the same ion m/e values as authentic PAF when analysed with g.c.-m.s. Lyso-PAF:acetyl-CoA acetyltransferase (EC 2.3.1.67) activity in human spermatozoa was also studied and showed similar kinetic parameters to those described for other cell systems. Stimulation of spermatozoa with progesterone and A23187 induced an increase of [3H]arachidonic acid release, suggesting an activation of phospholipase A. In conclusion, our results demonstrated increased production and release of PAF in human sperm following stimulation with progesterone and A23187 and suggest a role for this phospholipid in the activation of spermatozoa. PMID- 8503849 TI - Quantitative description of the absorption spectra of the coenzyme in glycogen phosphorylases based on log-normal distribution curves. AB - The absorption spectra of the coenzyme [pyridoxal 5'-phosphate (PLP)] in glycogen phosphorylase a (GPha), glycogen phosphorylase b (GPhb) and of the latter bound to various effectors and substrates were analysed on the basis of log-normal distribution curves. The results obtained showed that the ionization state of the PLP and GPha environment differs from that of GPhb. This divergence was interpreted in terms of tautomeric equilibria between some forms of the Schiff base of PLP and enzymic Lys-679. The ionic forms are slightly more predominant in GPha than they are in GPhb, so ionic and/or hydrogen-bonding interactions between the aromatic ring of PLP and GPha must be stronger than with GPhb. This confirms the purely structural role of the aromatic ring of the coenzyme. Binding of GPhb to AMP and Mg2+ results in the coenzyme adopting a similar state as in GPha. On the other hand, binding to IMP gives rise to no detectable changes in the tautomeric equilibrium of the coenzyme. PMID- 8503850 TI - Mitochondrial short-chain acyl-CoA dehydrogenase of human liver and kidney can function as an oxidase. AB - During an attempt to purify the peroxisomal acyl-CoA oxidases from human liver and kidney, we discovered a novel short-chain acyl-CoA oxidase, which was well separated from the known peroxisomal oxidases on various chromatographic columns. However, further experiments demonstrated that the novel oxidase is identical with the mitochondrial short-chain acyl-CoA dehydrogenase. (1) Subcellular fractionation revealed that the short-chain acyl-CoA oxidase is present in mitochondria and absent from peroxisomes. (2) The molecular mass (43 kDa) of the subunit of the purified oxidase was similar to that reported for the dehydrogenase. (3) The substrate spectrum of the oxidase was comparable with that described for the dehydrogenase. (4) On column chromatography, the oxidase and dehydrogenase activities co-eluted. Our results indicate that, in the absence of suitable electron acceptors, the short-chain acyl-CoA dehydrogenase is capable of transferring electrons directly to molecular oxygen, yielding potentially harmful H2O2. This raises the question as to whether the dehydrogenase might function as an oxidase in conditions in which the activity of the electron-transport chain is decreased, such as reperfusion after ischaemia. PMID- 8503851 TI - Ca(2+)-mediated prostaglandin E2 induction reduces haematoporphyrin-derivative induced cytotoxicity of T24 human bladder transitional carcinoma cells in vitro. AB - The effects of haematoporphyrin-derivative-mediated photodynamic treatment on arachidonic acid metabolism and its relation to clonogenicity have been studied in human bladder-tumour cells. Photodynamic treatment resulted in a transient release of arachidonic acid-derived compounds; prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) especially were strongly increased. This release was reduced by chelation of intracellular Ca2+ with Quin-2 or by lowering the extracellular Ca2+ concentration in the medium with EGTA, presumably resulting in inhibition of phospholipase A2. A similar reduction was obtained when indomethacin, an inhibitor of the cyclo-oxygenase pathway, was added prior to light exposure. These three treatments enhanced the photosensitivity, as revealed by the clonogenicity assay. Incubation with PGE2 prior to light exposure, but not with TXB2, protected against reproductive-cell death. The results of these experiments suggest that Ca(2+)-mediated activation of cyclo-oxygenase, resulting in increased levels of PGE2, participates in a cellular-defence mechanism against photodynamic cell killing. PMID- 8503852 TI - Regulation of urea and citrulline synthesis under physiological conditions. AB - Information on the regulation of urea synthesis in vivo was obtained by examining the relationship between ureagenesis in vivo, citrulline synthesis in vitro, and two factors currently hypothesized to exert short-term regulation of this pathway: the liver mitochondrial content of N-acetylglutamate (NAG) and substrate availability. Rats meal-fed for 4 h every day (4-20 schedule) or for 8 h every other day (8-40 schedule) were used. (1) The citrulline-synthesizing capacity of mitochondria from livers of rats on the 8-40 schedule exceeded the corresponding velocity of urea synthesis in vivo at all time points studied. (2) Mitochondrial NAG in these livers increased from 127 +/- 32 pmol/mg of protein at 0 h to 486 +/ 205 pmol/mg at 3 h after the start of a meal, and decreased thereafter, but the correlation between NAG content and the velocity of citrulline synthesis was not simple, suggesting that NAG is not the only determinant of the state of activation of carbamoyl phosphate synthase I. (3) In rats on the 4-20 schedule killed 1 h after the start of the meal, the liver content of ornithine, citrulline, arginine, glutamate, alanine and urea increased 2.1-12-fold with respect to the values at 0 h; glutamine decreased by 39%. (4) The combined findings indicate that in vivo, moment-to-moment control of the velocity of urea synthesis is exerted by substrate availability. (5) Digestion limits the supply of substrate to the liver, and prevents its ureagenic capacity from being overwhelmed following a protein-containing meal. PMID- 8503853 TI - Modulation of murine hepatic lipase activity by exogenous and endogenous Kupffer cell activation. AB - Deficiency of hepatic lipase (HL) may play a role in the lipoprotein abnormalities in chronic inflammatory states which are characterized by reticuloendothelial-system activation and cytokine release. HL triacylglycerol hydrolase activity was measured in heparin perfusates of livers from autoimmune MRL/lpr mice, which spontaneously develop a condition closely resembling human lupus erythematosis and exhibit spontaneous Kupffer-cell activation after 8 weeks of age, as well as from normal mice treated with Corynebacterium parvum or polyinosinic-polycytidylic acid complex [poly(I.C)] to induce Kupffer-cell activation. HL activity in MRL/lpr mice older than 8 weeks was 29.5% (P = 0.002) of that in age-matched control MRL/++ mice. Treatment of normal mice with C. parvum or poly(I.C) resulted in HL activities 18.6% (P = 0.004) and 13.1% (P = 0.007) respectively of untreated controls. Northern-blot hybridization of liver poly(A)+ RNA showed no differences in HL mRNA abundance in MRL/++ mice compared with the MRL/lpr autoimmune strain after 8 weeks of age, or in normal control mice compared with those treated with C. parvum, indicating attenuation of HL activity at the translational or post-translational level. Deficiency of this enzyme may represent one of the mechanisms contributing to the dyslipoproteinaemia of autoimmune disease and chronic infection. PMID- 8503854 TI - Glycogenolytic and haemodynamic responses to bovine serum albumin in isolated perfused livers from sensitized rats. AB - Infusion of BSA into isolated perfused livers of rats sensitized by intraperitoneal injection of BSA led to rapid increases in portal-vein pressure, glucose output and the lactate/pyruvate ratio in the effluent perfusate, with concomitant decreases in oxygen consumption and lactate+pyruvate efflux. The responses were attenuated at low (approximately 7 microM) perfusate Ca2+, but were restored on re-addition of normal Ca2+ concentration. Co-infusion of the cyclo-oxygenase inhibitor ibuprofen (50 microM) or of the platelet-activating factor receptor antagonist WEB 2170 (1.2 microM) inhibited haemodynamic responses to BSA (5 micrograms/ml) by 48% and 59% respectively. Responses to BSA were also attenuated by prior infusion of the beta-adrenergic agonist isoprenaline. Glycogen phosphorylase a activity was increased by 26% in livers freeze-clamped 2 min after onset of BSA infusion; tissue prostaglandin E2 content was increased at 2 min, but returned to control levels at 5 min. Homologous desensitization of hepatic responses to BSA was observed, but heterologous desensitization with heat aggregated IgG did not take place. It is concluded that livers from rats sensitized to antigen respond directly to subsequent antigen administration by vasoconstriction and glycogenolysis, and that autacoid mediators are involved in these responses. PMID- 8503855 TI - Synthesis of oligopeptide chloromethanes to investigate extended binding regions of proteinases: application to the interaction of fibrinogen with thrombin. AB - A method was established for the synthesis of oligopeptide chloromethanes which should be useful in the study of serine and cysteine proteinases with extended binding sites. The method involved condensation of an N-terminal peptide fragment obtained by solid-phase synthesis with a C-terminal peptide chloromethane synthesized by solution-phase chemistry. By using this procedure, oligopeptide chloromethanes of up to 16 residues were synthesized. These chloromethanes were based on the sequence of fibrinopeptide A. By using oligopeptide chloromethanes of different length, it was possible to show that the residues Asp7-Phe8-Leu9 play a crucial role in the recognition of fibrinopeptide A by thrombin. In contrast, the residues Ala1-Asp2-Ser3-Gly4-Glu5-Gly6 seem to play a minor role. Substitution of valine for Gly12, which occurs in a dysfibrinogenaemia, markedly decreased the rate of inactivation of thrombin by the oligopeptide chloromethane. The results are discussed in terms of the recently published structure of the complex between human thrombin and a chloromethane inhibitor based on fibrinopeptide A. PMID- 8503856 TI - Assembly of lipoprotein lipase in perfused guinea-pig hearts. AB - It has been suggested that lipoprotein lipase (LPL) can be assembled into its catalytically active dimeric form only after its oligosaccharide chains have been processed in the Golgi. To study this in a complete organ, LPL was metabolically labelled with [35S]methionine in perfused guinea-pigs hearts. After 10 min pulse labelling, LPL protein was eluted as two peaks from heparin-agarose: peak 1 at about 0.65 M NaCl, peak 2 at about 0.95 M NaCl. Catalytic activity was associated only with peak 2. Model studies with bovine LPL showed that active dimeric LPL is eluted in peak 2, but after treatments that dissociate the enzyme into inactive monomers it is eluted in peak 1. Pulse-labelled LPL in both peak 1 and peak 2 was fully sensitive to treatment with endoglycosidase (Endo) H. With chase, peak 1 disappeared and peak 2 acquired resistance to Endo H. These findings suggest that core glycosylated LPL is assembled into dimers already in the endoplasmic reticulum and that processing of the oligosaccharide chains occurs after dimerization. PMID- 8503857 TI - Simple methods for the detection and quantification of thiols from Crithidia fasciculata and for the isolation of trypanothione. AB - Methods for the qualitative and quantitative analysis of thiols by means of the fluorogenic reagent 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin are described, with particular reference to the trypanosomatid metabolites glutathionylspermidine (GSH-spermidine) and trypanothione. Second-order rate constants for the derivatization of seven different thiols under defined experimental conditions and at 21 degrees C varied between 619 +/- 34 and 10,560 +/- 236 M-1.s-1.T.l.c. of the thiols from Crithidia fasciculata was used to monitor the purification of trypanothione from this organism in three steps involving adsorption, ion-exchange and reversed-phase chromatography. The yield was approx. 50 mg of pure trypanothione from 100 g (wet wt.) of trypanosomatids. The method for the quantitative analysis of biological thiols is based on fluorometric detection after separation by reversed-phase or ion-paired chromatography on a phenyl-silica column. Analysis of the thiol composition of cell lysates prepared under nondenaturating conditions point to the rapid degradation of the GSH-spermidine conjugates. In addition to GSH, GSH-spermidine and trypanothione, at least one other prominent thiol was detected, and the contribution of this thiol to the total thiol content in the various growth phases of C. fasciculata was investigated. PMID- 8503858 TI - Conservation of a functionally important surface region between two families of the cytochrome P-450 superfamily. PMID- 8503859 TI - Fluorescence analysis of the interaction of isometamidium with Trypanosoma congolense. AB - Isometamidium chloride (Samorin) is the only compound recommended for prophylaxis against bovine trypanosomiasis in sub-Saharan Africa. The fluorescence property of this compound was used to investigate the interaction of the molecule with in vitro-derived bloodstream forms of Trypanosoma congolense IL 1180. Incubation of isometamidium with trypanosomes at 37 degrees C for 180 min resulted in a gradual alteration of the lambda max. with time (from 600 to 584 nm) and an increase in the intensity of trypanosome-associated fluorescence of approx. 2-fold. The alteration in fluorescence was temperature-dependent and inhibited by the addition of N-ethylmaleimide. In contrast, with intact cells addition of digitonin caused a rapid increase in fluorescence intensity to approximately four times that observed with intact cells. Uptake of isometamidium was also determined using radiolabelled drug; the results indicated that the time course of the uptake process resembled the fluorescence profile and was temperature dependent. The results therefore indicate that the alteration of fluorescence is due to interaction of isometamidium with an intracellular component(s) and that isometamidium is transported across the plasma membrane via a protein carrier. The data also indicate that the described fluorescence technique can be used to investigate the role of membrane transport in resistance to isometamidium. PMID- 8503860 TI - Mechanism of beta-carotene degradation. PMID- 8503861 TI - Rounding error, an unexpected fault in the output from a recording spectrophotometer: implications for model discrimination. AB - Although commonly ignored in discussions of experimental error, rounding may sometimes be the major source of error, especially with modern precision instruments: some recording spectrophotometers are optically and photometrically capable of making absorbance measurements with errors less than 0.0003, but provide no numerical information more precise than +/- 0.001. The problem may be diagnosed by a characteristic arrangement of points in a residual plot, which resembles the result of cutting a stroboscopic picture of a bouncing ball into several strips and modifying it by sliding the strips relative to one another to bring the points closer to the axis. Harmful effects of rounding error can be critical in experiments designed for model discrimination. PMID- 8503862 TI - Interaction of transcription factor Sp1 with the promoter of the gene for the multifunctional protein disulphide isomerase polypeptide. AB - Protein disulphide isomerase (PDI) is a unique polypeptide which resides in the lumen of the endoplasmic reticulum and also functions as the beta-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-binding protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a protein that binds various peptides in a specific manner. We have recently demonstrated that the promoter of the PDI gene contains six CCAAT boxes and other elements which are needed for efficient transcription. We now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-rich elements of the PDI promoter. Sp1 also appears to participate in the regulation of PDI gene expression, since overexpression of Sp1 stimulated PDI promoter activity in HeLa cells and mutations introduced into each of these Sp1-binding sites separately reduced the promoter strength, although even the largest decrease was only about 50%. These results support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, some of which are functionally redundant. PMID- 8503863 TI - Protein kinase C-dependent phosphorylation of annexins I and II in mesangial cells. AB - In this study we describe the phosphorylation of annexins from cultured rat mesangial cells by protein kinase C (PKC) both in vitro and in vivo. Annexins I and II were detected either by Western-blot analysis or by immunoprecipitation using specific antibodies. In the presence of [gamma-32P]ATP, cytosolic annexin I and annexin II were phosphorylated in vitro only when Ca2+ and phospholipids were added, but not in the presence of phospholipids alone. Annexin I was shown to be a better substrate than annexin II. In experiments in vivo performed on 32P labelled mesangial cells, the addition of two well-known activators of PKC, namely angiotensin II (AII) and phorbol myristate acetate (PMA), increased preferentially the phosphorylation of annexin I. Annexin II was phosphorylated to a much lesser extent after AII treatment. Phosphoamino acid analysis of annexins, either by two-dimensional chromatography or by using a specific antiphosphotyrosine antibody, revealed only phosphoserine in these experiments in vivo. The addition of AII to mesangial cells increased serine phosphorylation of annexin I and annexin II, whereas PMA only increased serine phosphorylation of annexin I. V8-protease phosphopeptide mapping of annexin I that was phosphorylated both in vitro and in vivo by PKC from mesangial cells shows similar phosphopeptides. PMID- 8503864 TI - Structural requirements for the interaction between tissue factor and factor VII: characterization of chymotrypsin-derived tissue factor polypeptides. AB - Tissue Factor (TF) is the cellular receptor for coagulation Factor VII/VIIa (FVII/VIIa). TF binds to FVIIa and promotes the rapid activation of the zymogen substrates Factors IX and X (FIX and FX) to the respective serine proteinases. In order to probe structure-function relationships in TF, we have subjected the truncated membrane-bound variant, TF 1-243, to proteolytic digestion in SDS containing gels. Three major polypeptide fragments were generated by proteolysis of TF 1-243 with chymotrypsin, producing cleavages C-terminal to residues 34, 76 and 103. All three polypeptides, TF 35-243, 77-243 and 104-243, bound biotinylated human FVII in a highly specific ligand blot assay. High-performance electrophoretic chromatography was used to isolated chymotrypsin-derived fragments of TF. These purified fragments bound FVII in ligand blots, and two of the three polypeptides exhibited much reduced, but significant, procoagulant activity in a chromogenic assay for the generation of Factor Xa in the presence of FVIIa and Ca2+. The smallest chymotrypsin-derived TF polypeptide, TF 104-243, showed reduced binding of FVII in ligand blot analyses, inhibited the activity of the full-length molecule, but had no procoagulant activity. These data suggest that a part of the binding site for FVII is contained within the TF sequence 104 243. The sequence TF 1-34 either contains a part of the FVII-binding domain or its removal leads to dysfunctional folding, disrupting binding sites elsewhere in the molecule. PMID- 8503865 TI - Stimulation of rat liver glycogen synthesis by the adenosine kinase inhibitor 5 iodotubercidin. AB - The adenosine kinase inhibitor 5-iodotubercidin (Itu) was found to have the following effects on glycogen metabolism in hepatocytes of fasted rats. (1) Itu strongly stimulated glycogen synthesis from different substrates (glucose, lactate plus pyruvate, dihydroxyacetone, glycerol and fructose). In cells incubated with these substrates, the well-known stimulating effect of amino acids and that of Itu was more than additive. (2) In parallel with the increase in glycogen deposition, there was an increase in synthase a and a decrease in phosphorylase a concentrations after administration of Itu. Synthase a was increased by Itu and amino acids in an additive manner, whereas the observed activation of phosphorylase after addition of amino acids was antagonized by Itu. (3) In contrast with amino acids, Itu increased neither the cell volume nor the aspartate and glutamate concentrations. (4) Itu enhanced the levels of cyclic AMP. The stimulation of glycogen deposition in the presence of Itu persisted when the cyclic AMP concentration was further increased by adenosine or 2 chloroadenosine. (5) Itu decreased the concentration of ATP, but its effects on glycogen synthesis, synthase a and phosphorylase a concentrations persisted when the ATP catabolism was prevented by adenosine. (6) The effect of Itu on glycogen synthesis was not the result of inhibition of adenosine kinase, since 5'-amino-5' deoxyadenosine, another inhibitor of this enzyme, had no effect on glycogen deposition. PMID- 8503866 TI - Intraluminal calcium of the liver endoplasmic reticulum stimulates the glucuronidation of p-nitrophenol. AB - The relationship between the intraluminal Ca2+ content of endoplasmic reticulum and the rate of the glucuronidation of p-nitrophenol was investigated in isolated rat hepatocytes. Different agents which decrease the Ca2+ level in the endoplasmic reticulum [calcium ionophores (A23187, ionomycin) or Ca(2+)-ATPase inhibitors(thapsigargin,2,5-di-(t-butyl)-1,4-benzohydroquinone+ ++)] inhibited the conjugation of p-nitrophenol. Depletion of intracellular Ca2+ stores by preincubation of hepatocytes in the absence of free Ca2+ (in the presence of excess EGTA) also decreased the rate of glucuronidation; Ca2+ re-admission to EGTA-treated hepatocytes restored glucuronidation. In intact liver microsomes the p-nitrophenol UDP-glucuronosyl-transferase activity was not modified by varying the external free Ca2+ concentrations within a cytosol-like range. Emptying of the Ca2+ from the lumen of microsomal vesicles by A23187, after MgATP-stimulated Ca2+ sequestration, decreased the glucuronidation of p-nitrophenol. A similar effect was observed in filipin-permeabilized hepatocytes. In native and in detergent-treated microsomes, Ca2+ (1-10 mM) increased the p-nitrophenol UDP glucuronosyltransferase activity. It is suggested that the physiological concentration of Ca2+ in the lumen of the endoplasmic reticulum is necessary for the optimal activity of p-nitrophenol UDP-glucuronosyltransferase; the depletion of Ca2+ decreases the activity of the enzyme. PMID- 8503868 TI - The molecular cloning of the squid (Loligo forbesi) visual Gq-alpha subunit and its expression in Saccharomyces cerevisiae. AB - The sequence of the alpha-subunit of the major G-protein from the squid (Loligo forbesi) retina was predicted from its cDNA to be a member of the Gq subclass. The abundance of the squid Gq-alpha in the squid photoreceptor membranes suggests that the protein functions in phototransduction; the sequence of this G-protein is consistent with it mediating the light-dependent activation of a phospholipase C. The squid G-alpha was expressed in the yeast Saccharomyces cerevisiae, where it was unable to replace the function of GPA1, the yeast G-alpha homologue that regulates the mating response, suggesting that Gq-alpha was unable to interact with the endogenous G-beta gamma (STE4-STE18). PMID- 8503867 TI - Cellular signalling mechanisms in B lymphocytes. PMID- 8503870 TI - A computer program for the algebraic determination of control coefficients in Metabolic Control Analysis. AB - A computer program (MetaCon) is described for the evaluation of flux control, concentration control and branch-point distribution control coefficients of a metabolic pathway. Requiring only the reaction scheme as input, the program produces algebraic expressions for the control coefficients in terms of elasticity coefficients, metabolite concentrations and pathway fluxes. Any of these variables can be substituted by numeric or simple algebraic expressions; the expressions will then be automatically rearranged in terms of the remaining unknown variables. When all variables have been substituted, numeric values will be obtained for the control coefficients. The program is a computerized implementation of the matrix method for the determination of control coefficients. The features of MetaCon are compared with those of other programs available to workers in Metabolic Control Analysis. Potential benefits of, and methods of using, MetaCon are discussed. The mathematical background and validity of the matrix method rules are discussed, and the algorithm used by MetaCon is described. The matrix method is shown to be a specific case of a previously described general formalism for calculating control coefficients. PMID- 8503869 TI - Expression of ferrochelatase mRNA in erythroid and non-erythroid cells. AB - Ferrochelatase, which catalyses the last step in haem biosynthesis, i.e. the insertion of Fe(II) into protophorphyrin IX, is present in all cells, but is particularly abundant in erythroid cells during haemoglobinization. Using mouse ferrochelatase cDNA as a probe two ferrochelatase transcripts, having lengths of 2.9 kb and 2.2 kb, were found in extracts of mouse liver, kidney, brain, muscle and spleen, the 2.9 kb transcript being more abundant in the non-erythroid tissues and the 2.2 kb transcript more predominant in spleen. In mouse erythroleukemia cells the 2.9 kb ferrochelatase transcript is also more abundant; however, following induction of erythroid differentiation by dimethyl sulphoxide there is a preferential increase in the 2.2 kb transcript, which eventually predominates. With mouse reticulocytes, the purest immature erythroid cell population available, over 90% of the total ferrochelatase mRNA is present as the 2.2 kb transcript. Since there is probably only one mouse ferrochelatase gene, the occurrence of two ferrochelatase transcripts could arise from the use of two putative polyadenylation signals in the 3' region of ferrochelatase DNA. This possibility was explored by using a 389 bp DNA fragment produced by PCR with synthetic oligoprimers having sequence similarity with a region between the polyadenylation sites. This fragment hybridized only to the 2.9 kb ferrochelatase transcript, indicating that the two transcripts differ at their 3' ends and suggesting that the 2.2 kb transcript results from the utilization of the upstream polyadenylation signal. The preferential utilization of the upstream polyadenylation signal may be an erythroid-specific characteristic of ferrochelatase gene expression. PMID- 8503871 TI - A physiological role of Mn2+ in the regulation of cytosolic phosphoenolpyruvate carboxykinase from rat liver is unlikely. AB - A cytosolic cell-free system prepared from rat liver was used to study the effect of bivalent cations on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Steady-state concentrations of oxaloacetate in the range 5-50 microM were generated from increasing concentrations of malate+fumarate (10:1); 2 mM ITP and 3 mM Mg2+ were added as cofactors. Micromolar concentrations of Mn2+, Fe2+ and, to a lesser extent, of Zn2+ and Co2+ were shown to stimulate PEPCK activity. Vmax. (mumol/min per g of liver) increased from 0.67 to 1.68 on addition of 5 microM Fe2+ and to 2.34 with 2 microM Mn2+, whereas no significant effect on the Km for oxaloacetate was observed. The apparent K(a) values (total) were 0.62 microM for Mn2+, 1.48 microM for Zn2+, 1.92 microM for Co2+ and 3.37 microM for Fe2+, being 2-8-fold lower than the corresponding published values. Variations of the free Mn2+ concentration were obtained (a) by increasing the Mn2+ concentration (i.e. activation curve) and (b) by simultaneous addition of Mn2+ and increasing concentrations of the chelating agent EGTA (i.e. inactivation curve). Different results were obtained for the activation and inactivation curves. The inactivation curve showed that PEPCK activity was almost unaffected by variations of the free Mn2+ concentration over the range 0.05-0.15 microM. Under comparable experimental conditions, rat liver arginase (another Mn(2+)-dependent enzyme) was completely inactivated. From kinetic evidence, the existence of two distinct molecular forms of cytosolic rat liver PEPCK with different Mn2+ affinities is postulated. Considering the high affinity of PEPCK for Mn2+ and its relative insensitivity to changes in the free Mn2+ concentration, it seems rather unlikely that changes in the free cation concentration play a major role in regulating PEPCK activity in vivo. PMID- 8503872 TI - Glutathione analogue sorbents selectively bind glutathione S-transferase isoenzymes. AB - Novel affinity sorbents for glutathione S-transferases (GSTs) were created by binding glutathione (GSH) analogues to Sepharose 6B. The GSH molecule was modified at the glycine moiety and at the group attached to the sulphur of cysteine. When tested by affinity chromatography in a flow-through microplate format, several of these sorbents selectively bound GST isoenzymes. gamma E-C(Hx) phi G (glutathione with a hexyl moiety bound to cysteine and phenylglycine substituted for glycine) specifically bound rat GST 7-7, the Pi-class isoenzyme, from liver, kidney and small intestine. gamma E-C(Bz)-beta A (benzyl bound to cysteine and beta-alanine substituted for glycine) was highly selective for rat subunits 3 and 4, which are Mu-class isoenzymes. By allowing purification of the isoenzymes under mild conditions that preserve activity, the novel sorbents should be useful in characterizing the biological roles of GSTs in both normal animal and cancer tissues. PMID- 8503873 TI - Glutathione S-transferases in rat olfactory epithelium: purification, molecular properties and odorant biotransformation. AB - The olfactory epithelium is exposed to a variety of xenobiotic chemicals, including odorants and airborne toxic compounds. Recently, two novel, highly abundant, olfactory-specific biotransformation enzymes have been identified: cytochrome P-450olf1 and olfactory UDP-glucuronosyltransferase (UGT(olf)). The latter is a phase II biotransformation enzyme which catalyses the glucuronidation of alcohols, thiols, amines and carboxylic acids. Such covalent modification, which markedly affects lipid solubility and agonist potency, may be particularly important in the rapid termination of odorant signals. We report here the identification and characterization of a second olfactory phase II biotransformation enzyme, a glutathione S-transferase (GST). The olfactory epithelial cytosol shows the highest GST activity among the extrahepatic tissues examined. Significantly, olfactory epithelium had an activity 4-7 times higher than in other airway tissues, suggesting a role for this enzyme in chemoreception. The olfactory GST has been affinity-purified to homogeneity, and shown by h.p.l.c. and N-terminal amino acid sequencing to constitute mainly the Yb1 and Yb2 subunits, different from most other tissues that have mixtures of more enzyme classes. The identity of the olfactory enzymes was confirmed by PCR cloning and restriction enzyme analysis. Most importantly, the olfactory GSTs were found to catalyse glutathione conjugation of several odorant classes, including many unsaturated aldehydes and ketones, as well as epoxides. Together with UGT(olf), olfactory GST provides the necessary broad coverage of covalent modification capacity, which may be crucial for the acuity of the olfactory process. PMID- 8503874 TI - Oxidant stress inhibits the store-dependent Ca(2+)-influx pathway of vascular endothelial cells. AB - Oxidant stress induced by t-butyl hydroperoxide (t-BuOOH) inhibits bradykinin stimulated Ca2+ signalling in vascular endothelial cells. The effect of t-BuOOH on intracellular Ca2+ pools was determined by addition of Ca(2+)-releasing agents to fura-2-loaded cells suspended in Ca(2+)-free/EGTA buffer. In control cells, sequential additions of bradykinin and ionomycin produced similar increases in cytosolic free [Ca2+] ([Ca2+]i). By contrast, incubation with t-BuOOH progressively decreased the response of [Ca2+]i to bradykinin and increased that to ionomycin, suggesting that the total (ionomycin-releasable) Ca2+ pool remains replete during oxidant stress. The effect of t-BuOOH on the InsP3-sensitive Ca2+ pool was measured by the increase in [Ca2+]i or efflux of 45Ca2+ stimulated by 2,5-di-t-butylhydroquinone (BHQ). Incubation with t-BuOOH did not inhibit BHQ stimulated increases in [Ca2+]i or 45Ca2+ efflux, suggesting that the InsP3 sensitive Ca2+ pool remains replete and releasable. Activity of the Ca(2+)-influx pathway stimulated by release of internal Ca2+ stores was determined via re addition of Ca2+ to BHQ-stimulated cells suspended in Ca(2+)-free/EGTA buffer and via BHQ-stimulated 45Ca2+ uptake. Incubation of cells with t-BuOOH for 1 h significantly inhibited the influx pathway. At later time points, t-BuOOH increased basal [Ca2+]i and potentiated the response of [Ca2+]i to BHQ. Similar results were demonstrated with thapsigargin. Together, these findings suggest that (1) the inhibitory effect of t-BuOOH on bradykinin-stimulated release of Ca2+ from internal stores is not related to depletion of these stores, and (2) inhibition of the store-dependent Ca(2+)-influx pathway occurs by a direct effect of the influx pathway or by inhibition of the mechanism which links the internal Ca2+ store to plasmalemmal Ca2+ influx. PMID- 8503875 TI - Co-culture of embryonic chick heart cells and ciliary ganglia induces parasympathetic responsiveness in embryonic chick heart cells. AB - We have developed a system for the co-culture of embryonic chick heart cells obtained from embryos at 3.5 days in ovo with ciliary ganglia from chick embryos at 7 days in vivo. After 3 days of co-culture, removal of the ciliary ganglia resulted in complete degeneration of axons within 6-8 h, leaving the post innervated heart cell culture devoid of neurons. Embryonic chick heart cells at 3.5 days in ovo are unresponsive to muscarinic stimulation. However, following 3 days of co-culture with ciliary ganglia, the heart cells developed a negative chronotropic response to muscarinic stimulation (paired t test, P < 0.02) which persisted for at least 24 h after removal of the ciliary ganglion. The development of muscarinic responsiveness was associated with an increase in the levels of specific alpha-subunits of the guanine nucleotide binding proteins (G proteins), with a 3-fold increase in the level of alpha 39 (39 kDa subunit) and a 2.5-fold increase in the level of alpha 41. The level of the G-protein subunit alpha s remained unchanged. Culture of embryonic chick heart cells at 3.5 days in ovo with medium conditioned by the growth of embryonic chick heart cells and ciliary ganglia had an effect on the chronotropic response to muscarinic stimulation and on alpha 39 and alpha 41 levels identical to that of co-culture. These data suggest that a soluble factor released during the co-culture of embryonic chick heart cells and ciliary ganglia is capable of inducing muscarinic responsiveness. These studies suggest that innervation of the heart may induce parasympathetic responsiveness by increasing the availability of G-proteins which couple the muscarinic receptor to a physiological response. PMID- 8503876 TI - Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria. AB - Plant tissues contain highly conjugated forms of folate. Despite this, the ability of plant folate-dependent enzymes to utilize tetrahydrofolate polyglutamates has not been examined in detail. In leaf mitochondria, the glycine cleavage system and serine hydroxymethyltransferase, present in large amounts in the matrix space and involved in the photorespiratory cycle, necessitate the presence of tetrahydrofolate as a cofactor. The aim of the present work was to determine whether glutamate chain length (one to six glutamate residues) influenced the affinity constant for tetrahydrofolate and the maximal velocities displayed by these two enzymes. The results show that the affinity constant decreased by at least one order of magnitude when the tetrahydrofolate substrate contained three or more glutamate residues. In contrast, maximal velocities were not altered in the presence of these substrates. These results are consistent with analyses of mitochondrial folates which revealed a pool of polyglutamates dominated by tetra and pentaglutamates. The equilibrium constant of the serine hydroxymethyltransferase suggests that, during photorespiration, the reaction must be permanently pushed toward the formation of serine (the unfavourable direction) to allow the recycling of tetrahydrofolate necessary for the operation of the glycine decarboxylase T-protein. PMID- 8503877 TI - Changes in rates of glucose utilization and regulation of glucose disposal by fast-twitch skeletal muscles in late pregnancy. AB - Glucose utilization indices (GUI) were measured in vivo in conjunction with active pyruvate dehydrogenase complex (PDH(a) and glycogen synthase (GS) activities in fast-twitch skeletal muscles [extensor digitorum longus (EDL), tibialis anterior and gastrocnemius] of late-pregnant rats and age-matched virgin control rats in the fed state, after 24 h starvation and at 2 h after re-feeding with standard laboratory chow ad libitum after 24 h starvation. As demonstrated previously [Holness and Sugden (1990) Biochem. J 277, 429-433], GUI values of fast-twitch skeletal muscles of virgin rats were low in the fed ad libitum and the 24 h-starved states, but dramatically increased after subsequent chow re feeding. GUI values of fast-twitch skeletal muscles of late-pregnant rats were also low in the fed and starved states and were increased by re-feeding, but the increase in GUI values elicited by re-feeding was greatly attenuated. PDHa activities in EDL, tibialis anterior and gastrocnemius in the fed state were unaffected by late pregnancy, and skeletal-muscle PDHa activities were decreased after 24 h of starvation in both groups. Whereas re-feeding of virgin rats with standard diet for 2 h restored PDHa activities in fast-twitch skeletal muscles to values for rats continuously fed ad libitum, PDHa activities in fast-twitch skeletal muscles of late-pregnant rats, although increased in response to re feeding, remained considerably less than the corresponding fed ad libitum values after 2 h of re-feeding. In contrast, neither skeletal-muscle GS re-activation nor rates of skeletal-muscle glycogen deposition after re-feeding were markedly affected by late pregnancy. The results are discussed in relation to the specific targeting of individual pathways of glucose disposal in fast-twitch skeletal muscles during re-feeding in late pregnancy. PMID- 8503878 TI - Photoaffinity labelling of smooth-muscle myosin by methylanthraniloyl-8-azido ATP. AB - Methylanthraniloyl-8-azido-ATP (Mant-8-N3-ATP), which binds to the 20 kDa C terminal tryptic fragment of skeletal-muscle myosin subfragment-1 [Maruta, Miyanishi and Matsuda (1989) Eur. J. Biochem. 184, 213-221], was synthesized and used as a probe of the conformational change of smooth-muscle myosin. Mant-8-N3 ATP, like ATP, induced the formation of the 10 S conformation at low ionic strength. In the presence of vanadate, smooth-muscle myosin formed a stable complex with Mant-8-N3-ADP, and this complex showed the 10 S-->6 S transition of myosin. ATP-binding sites for 6 S (extended state) and 10 S (folded state) myosin were studied by photolabelling of myosin with Mant-8-N3-ADP. For both 6 S and 10 S myosin, Mant-8-N3-ATP was incorporated into the 29 kDa N-terminal tryptic fragment of myosin heavy chain. This is unlike the labelling of skeletal-muscle myosin, in which the 20 kDa C-terminal fragment is labelled. The labelling of 29 kDa fragment was diminished significantly by addition of ATP. These results suggest that the conformation of the ATP-binding site of smooth-muscle myosin is different from that of skeletal-muscle myosin. To examine further the possible differences in the labelling site between 6 S and 10 S myosin, the affinity labelled 29 kDa fragment was subjected to complete proteolysis by lysylendo peptidase. The fluorescent-labelled-peptide map suggested that the Mant-8-N3-ADP binding sites for 6 S and 10 S myosin were identical. PMID- 8503879 TI - Comparative kinetic study between native and chemically modified Cu,Zn superoxide dismutases. AB - The kinetic behaviour of native bovine erythrocyte Cu,Zn superoxide dismutase (N SOD) and of its derivatives by reaction with polyethylene glycol, acetic and succinic anhydrides has been investigated here in detail. Their responses to changes of pH and ionic strength (I) have been used as a probe for quantitatively displaying the relevance to kinetic rate constant of superficial positive charges driving the superoxide ion (O2-) toward the enzyme's active site. Overall kinetic trends indicate that this long-range O2- electrostatic guidance is essentially due to the positive charges of the amino-acid residues Lys-120 and Lys-134 which are strategically located around the active site. The comparison between the kinetic data obtained from N-SOD and those from polyethylene-glycolated SOD (PEG SOD) enabled us to state that in PEG-SOD an O2(-)-steering positive electrostatic force, halved in comparison with N-SOD, is still operating, and that only Lys-120 is linked in the reaction of N-SOD with PEG. Elimination of the electrostatic driving force, carried out either by deprotonation of lysine amino groups at high pH, or by their neutralization with succinic anhydride and acetic anhydride, or by ionic screening at high ionic strength, always lowered the kinetic rate constant to a value of approx. 3 x 10(8) M-1.s-1. This value is about 15 times smaller than that measured in the presence of the reactant-steering mechanism and represents the k value of the reaction limited by pure diffusion. Finally, the kinetic behaviour of acetylated SOD and succinylated SOD demonstrated the inhibitor effect of OH- at strongly alkaline pH. PMID- 8503880 TI - Formic acid is a product of the alpha-oxidation of fatty acids by human skin fibroblasts: deficiency of formic acid production in peroxisome-deficient fibroblasts. AB - Human skin fibroblasts in culture can oxidize beta-methyl fatty acids, such as phytanic acid and 3-methylhexadecanoic acid, to CO2 and water-soluble products. The latter are released largely into the culture medium. The major water-soluble product formed from [1-14C]phytanic and [1-14C]3-methylhexadecanoic acids is [14C]formic acid. As phytanic acid and 3-methylhexadecanoic acids contain beta methyl groups and theoretically cannot be degraded by beta-oxidation, we postulate that formic acid is formed from fatty acids by alpha-oxidation. The marked reduction in formic acid production from beta-methyl fatty acids in peroxisome-deficient skin fibroblasts suggests that peroxisomes are involved in the generation of C1 units. PMID- 8503881 TI - Indication of possible post-translational formation of disulphide bonds in the beta-sheet domain of human lysozyme. AB - Lysozyme has two distinct folding domains, and in most molecules the alpha helical domain folds more quickly than the beta-sheet domain in vitro [Radford, Dobson and Evans (1992) Nature (London) 358, 302-307]. In order to investigate the relationship between the formation of disulphide bonds and protein folding in vivo, we carried out cysteine scanning mutagenesis to shift positions of the disulphide bonds in both the alpha-helical and beta-sheet domains of human lysozyme. Of the constructed mutants (nine in the beta-sheet domain and 13 in the alpha-helical domain), the mutant L79CC81A, in which Leu-79 and Cys-81 in the beta-sheet domain were replaced by Cys and Ala respectively, was secreted by yeast. The rest of the mutants were retained in the insoluble fraction of the cell, probably because of a failure of folding. The distance between the two alpha-carbons at positions 79 and 95 in the wild-type protein is too far to form a disulphide bond, but analysis of the primary structure revealed that the major part of L79CC81A was secreted with a non-native disulphide bond Cys79-Cys95 and two free cysteine residues at positions 65 and 77 in the beta-sheet domain. These results suggest that the beta-sheet domain of human lysozyme can tolerate the shift of locations of disulphide bonds, and the non-native folding of mutated polypeptide chains in in vivo folding. The free residues Cys-65 and Cys-77 formed a disulphide bond in vitro by air oxidation, yielding two isomers. On the basis of our previous results and present study it is suggested that the formation of Cys6-Cys128 is the first step of the in vivo correct folding of human lysozyme, and disulphide bonds in the beta-sheet domain are post-translationally formed in vivo. PMID- 8503882 TI - Depletion of tumour glutathione in vivo by buthionine sulphoximine: modulation by the rate of cellular proliferation and inhibition of cancer growth. AB - We have investigated in Ehrlich-ascites-tumour-bearing mice the effect of buthionine sulphoximine (BSO), a selective inhibitor of GSH synthesis, on the rate of GSH depletion of tumour versus normal tissues and its relation to tumour cell proliferation. In normal tissues, GSH and GSSG remain unchanged or close to normal values during tumour growth, even at the last stage of growth when the animal is close to death. After administration of a single dose of BSO (4 mmol/kg), the rates of GSH depletion and recovery in the tumour and in several normal tissues are very different. BSO depletes GSH in cancer cells to a level of 0.3-0.4 mumol/g. The fall in GSH levels is faster when tumour cells do not proliferate actively. Four treatments of 4 mmol of BSO/kg at 48 h intervals induce a significant decrease (about 44%) in tumour growth. Our data show that the rate of BSO-induced GSH depletion in cancer cells depends on the stage of tumour growth, and that BSO administration also inhibits cancer-cell proliferation. A mechanism involving changes in protein kinase C activity and intracellular pH is proposed to explain the inhibition of cancer growth elicited by BSO. PMID- 8503883 TI - Investigation of the subcellular location of the tetrapyrrole-biosynthesis enzyme coproporphyrinogen oxidase in higher plants. AB - The subcellular location of two enzymes in the biosynthetic pathway for protoporphyrin IX, coproporphyrinogen (coprogen) oxidase (EC 1.3.3.3) and protoporphyrinogen (protogen) oxidase (EC 1.3.3.4) has been investigated in etiolated pea (Pisum sativum) leaves and spadices of cuckoo-pint (Arum maculatum). Plant tissue homogenized in isotonic buffer was subjected to subcellular fractionation to prepare mitochondria and plastids essentially free of contamination by other cellular organelles, as determined by marker enzymes. Protogen oxidase activity measured fluorimetrically was reproducibly found in both mitochondria and etioplasts. In contrast, coprogen oxidase could be detected only in etioplasts, using either a coupled fluorimetric assay or a sensitive radiochemical method. The implications of these results for the synthesis of mitochondrial haem in plants is discussed. PMID- 8503884 TI - Phosphatidylcholine is a major source of phosphatidic acid and diacylglycerol in angiotensin II-stimulated vascular smooth-muscle cells. AB - In cultured vascular smooth-muscle cells, angiotensin II produces a sustained formation of diacylglycerol (DG) and phosphatidic acid (PtdOH). Since the fatty acid composition of these molecules is likely to determine their efficacy as second messengers, it is important to ascertain the phospholipid precursors and the biochemical pathways from which they are produced. Our experiments suggest that phospholipase D (PLD)-mediated phosphatidylcholine (PtdCho) hydrolysis is the major source of both DG and PtdOH during the late signalling phase. First, in cells labelled with [3H]myristate, which preferentially labels PtdCho, formation of [3H]PtdOH precedes formation of [3H]DG. Second, in contrast with phospholipase C (PLC) activation, DG mass accumulation is dependent on extracellular Ca2+. Similarly, DG mass accumulation is not attenuated by protein kinase C activation, which we have previously shown to inhibit the phosphoinositide-specific PLC. Third, the fatty acid composition of late-phase DG and PtdOH more closely resembles that of PtdCho than that of phosphatidylinositol. Finally, in cells labelled for a short time with [3H]glycerol, the radioactivity incorporated into [3H]DG and PtdOH was greater than that incorporated into PtdIns, but not into PtdCho. We found no evidence that synthesis de novo or phosphatidylethanolamine breakdown contributes to sustained DG and PtdOH formation. Thus, in angiotensin II-stimulated cultured vascular smooth-muscle cells, PLD-mediated PtdCho hydrolysis is the major source of sustained DG and PtdOH, whereas phosphoinositide breakdown is a minor contributor. Furthermore, PtdOH phosphohydrolase, which determines the relative levels of DG and PtdOH, appears to be regulated by protein kinase C. These results have important implications for the role of these second messengers in growth and contraction. PMID- 8503885 TI - Stimulation of lipoprotein lipase synthesis by refeeding, insulin and dexamethasone. AB - Lipoprotein lipase synthesis in adipose tissue was greater in rats fed ad libitum or refed than in fasted rats. Insulin alone and together with dexamethasone increased lipoprotein lipase synthesis in adipose tissue incubated in vitro. The changes in relative lipoprotein lipase synthesis (immunoprecipitable 35S-labelled lipoprotein lipase as a fraction of general [35S]protein after pulse-labelling with [35S]methionine) indicate that insulin and dexamethasone exert a selective effect on lipoprotein lipase synthesis. There was no evidence for an inverse relationship between lipoprotein lipase synthesis and activity for any of the conditions studied. PMID- 8503886 TI - N-3-hydroxypropionyl-alpha-D-perosamine homopolymer constituting the O-chain of lipopolysaccharides from Vibrio bioserogroup 1875 possessing antigenic factor(s) in common with O1 Vibrio cholerae. AB - A structural study was performed by 13C-n.m.r. spectroscopy and methylation analysis of the O-chain of lipopolysaccharide (LPS) from Vibrio bioserogroup 1875 possessing antigenic factor(s) in common with O1 Vibrio cholerae. It was demonstrated to contain a linear homopolymer of (1-->2)-linked N-3 hydroxypropionyl-alpha-D-perosamine [4-(3-hydroxypropanamido)-4,6-dideoxy-alpha-D mannopyranose], which is very similar to, but not identical with, both (1-->2) linked linear N-3-deoxy-L-glycero-tetronyl(S-2,4-dihydroxybutyryl)-alpha-D - perosamine homopolymer and (1-->2)-linked linear N-acetyl-alpha-D-perosamine homopolymer which constitute the O-chains of O1 V. cholerae and non-O1 V. cholerae bioserogroup Hakata LPS respectively. PMID- 8503887 TI - A dramatic change in the rate-limiting step of beta-lactam hydrolysis results from the substitution of the active-site serine residue by a cysteine in the class-C beta-lactamase of Enterobacter cloacae 908R. AB - A cysteine residue has been substituted for the active-site serine of the class-C beta-lactamase produced by Enterobacter cloacae 908R by site-directed mutagenesis. The modified protein exhibited drastically reduced kcat./Km values on all tested substrates. However, this decrease was due to increased Km values with some substrates and to decreased kcat. values with others. These apparently contradictory results could be explained by a selective influence of the mutation on the first-order rate constant characteristic of the acylation step, a hypothesis which was confirmed by the absence of detectable acylenzyme accumulation with all the tested substrates, with the sole exception of cefoxitin. PMID- 8503888 TI - Nitroglycerin metabolism in vascular tissue: role of glutathione S-transferases and relationship between NO. and NO2- formation. AB - Nitroglycerin is a commonly employed pharmacological agent which produces vasodilatation by release of nitric oxide (NO.). The mechanism by which nitroglycerin releases NO. remains undefined. Recently, glutathione S transferases have been implicated as important contributors to this process. They are known to release NO2- from nitroglycerin, but have not been shown to release NO.. The present studies were designed to examine the role of endogenous glutathione S-transferases in this metabolic process. Homogenates of dog carotid artery were incubated anaerobically with nitroglycerin, and NO. and NO2- production was determined by chemiluminescence. The role of glutathione S transferases was studied by incubating homogenates with nitroglycerin in the presence of 1 mM GSH or 1 mM S-hexyl-glutathione, a potent inhibitor of glutathione S-transferases. Homogenates released 163 pmol of NO./h per mg of protein from nitroglycerin, and 2370 pmol of NO2-/h per mg. Adding GSH decreased NO. production by 82% and increased NO2- production by 98%. S-Hexylglutathione inhibited glutathione S-transferase activity by 96% and decreased NO2- production by 78%, but had no effect on NO. release. A linear relationship between glutathione S-transferase activity and NO2- production was observed, whereas glutathione S-transferase activity and NO. release were unrelated. Western-blot analysis demonstrated that dog carotid vascular smooth muscle contained Pi and Mu forms of glutathione S-transferases, with a predominance of the former. Purified preparations of human Pi and rat Mu isoforms metabolized nitroglycerin only to NO2- and not to NO.. On the basis of these findings, we conclude that (1) glutathione S-transferases do not contribute to the bioconversion of nitroglycerin to NO., but instead act as a degradative pathway for nitroglycerin, and (2) the release of NO. from nitroglycerin is not dependent on the formation of NO2-. PMID- 8503889 TI - Cell- and inducer-specific accretion of human isometallothioneins. AB - The synthesis of metallothionein (MT) was investigated in three different human epithelial cell lines, each derived from one of the embryonic germ layers. The accretion of different isoforms of the protein was monitored using a sensitive neutral-pH h.p.l.c. method. Induction of MT synthesis by zinc ions and dexamethasone revealed differences between the three cell lines, both with respect to the number and the amounts of the different isoMTs formed. Dose response experiments showed that an increase in dexamethasone concentration enhances MT accretion asymptotically to a limit, whereas within the concentration range explored zinc produces an exponential augmentation. PMID- 8503890 TI - Characterization of the sporulation-related gamma-D-glutamyl-(L)meso diaminopimelic-acid-hydrolysing peptidase I of Bacillus sphaericus NCTC 9602 as a member of the metallo(zinc) carboxypeptidase A family. Modular design of the protein. AB - The sporulation-related gamma-D-glutamyl-(L)meso-diaminopimelic-acid-hydrolysing peptidase I of Bacillus sphaericus NCTC 9602 has been analysed by proton-induced X-ray emission. It contains 1 equivalent Zn2+ per mol of protein. As derived from gene cloning and sequencing, the B. sphaericus Zn peptidase I is a two-module protein. A 100-amino-acid-residue N-terminal domain consisting of two tandem segments of similar sequences, is fused to a 296-amino-acid-residue C-terminal catalytic domain. The catalytic domain belongs to the Zn carboxypeptidase A family, the closest match being observed with the Streptomyces griseus carboxypeptidase [Narahashi (1990) J. Biochem. 107, 879-886] and with the family prototype, bovine carboxypeptidase A. The catalytic domain of the B. sphaericus peptidase I possesses, distributed along the amino-acid sequence, peptide segments, a triad His162-Glu165-His307 and a dyad Tyr347-Glu366 that are equivalent to secondary structures, the zinc-binding triad His69-Glu72-His196 and the catalytic dyad Tyr248-Glu270 of bovine carboxypeptidase A respectively. The N terminal repeats of the B. sphaericus peptidase I have similarity with the C terminal repeats of the Enterococcus hirae muramidase 2, the Streptococcus (now Enterococcus) faecalis autolysin and the Bacillus phi PZA and phi 29 lysozymes, to which a role in the recognition of a particular moiety of the bacterial cell envelope has been tentatively assigned. Detergents enhance considerably the specific activity of the B. sphaericus peptidase I. PMID- 8503891 TI - Over-expression of a functionally active human GM2-activator protein in Escherichia coli. AB - The cDNA of the human GM2-activator protein was cloned into the expression vector pHX17. The plasmid encodes a fusion protein with a hexahistidine tail and a Factor Xa cleavage site at its N-terminus. The recombinant protein was purified from cell homogenates under denaturing conditions by metal-ion affinity chromatography in a single step and then was refolded. The hexahistidine tail could be removed when desired by digestion with Factor Xa. In a functional assay, the GM2-activator thus generated from Escherichia coli and renatured, with or without the hexahistidine tail, was as active as the native GM2-activator protein that was purified from human tissue. When added to the culture medium, the recombinant carbohydrate-free GM2-activator, carrying the hexahistidine tail, could be taken up efficiently and restored the degradation of ganglioside GM2 to normal rates in mutant fibroblasts with the AB variant of GM2-gangliosidosis, which is characterized by a genetic defect in the GM2-activator protein. The prokaryotic expression system is useful for producing milligram quantities of a pure and functionally active GM2-activator. PMID- 8503892 TI - Role of a membrane-associated serine esterase in the oxidant activation of phospholipase A2 by t-butyl hydroperoxide. AB - Exposure of bovine pulmonary-arterial endothelial cells to the oxidant lipid t butyl hydroperoxide (t-Bu-OOH) increases cell-membrane-associated phospholipase A2 (PLA2) activity and stimulates arachidonic acid (AA) release. To test the hypothesis that a membrane-associated serine esterase plays an important role in activating PLA2, the present study was undertaken. In addition to increasing PLA2 activity and AA release, t-Bu-OOH also enhances the activity of a membrane associated serine esterase that cleaves the synthetic substrate N alpha-p-tosyl-L arginine methyl ester (TAME). Changes in the activity of this membrane-bound serine esterase correlate directly with changes in the activity of PLA2. Serine esterase inhibitors such as phenylmethanesulphonyl fluoride, di-isopropyl fluorophosphate and alpha 1-proteinase inhibitor, and TAME, a synthetic substrate for serine esterase, prevent the increase in serine esterase activity, PLA2 activity and AA release caused by t-Bu-OOH. Pretreatment of the endothelial cells with the antioxidant vitamin E prevents t-Bu-OOH-induced stimulation of AA release and the cell-membrane-associated serine esterase and PLA2 activities. Adding t-Bu-OOH or the serine esterase trypsin to the endothelial-cell membrane fraction also significantly augments PLA2 activity, implying that these treatments activate latent PLA2. These results suggest that t-Bu-OOH stimulates a membrane-associated serine esterase that plays a crucial role in activating PLA2 and releasing AA. PMID- 8503893 TI - Induction of metallothionein synthesis by cadmium and zinc in cultured rabbit kidney cells (RK-13). AB - The effects of increasing concentrations of Zn(II) and Cd(II) on the expression of the four isometallothioneins (isoMTs), namely MT-1a, MT-2a, MT-2d and MT-2e, in rabbit kidney cells (RK-13) and the development of cellular tolerance to these metal ions were studied. The results showed that, whereas in parental cells MT concentration was low and composed nearly exclusively of MT-2a and MT-1a, all four isoMTs increased massively in abundance when the cells were exposed to toxic concentrations of Zn(II) or Cd(II), the relative increase being largest in the two minor isoforms MT-2d and MT-2e. While the response of the four isoMTs to the challenge by Zn(II) or Cd(II) was qualitatively comparable, there were differences in sensitivity and delay time, Cd(II) being the more efficient inducer and much faster in eliciting the onset of isoMT synthesis. An even larger production of isoMTs resulted when RK-13 cells were cultured in the presence of a series of metal concentrations yielding sub-lines of increased metal tolerance. In this instance too, there were marked differences in the response to Cd(II) and Zn(II). Thus, in cells of sub-lines selected for tolerance to moderate concentrations of Cd(II) the kinetic analysis of isoMT accretion gave indications of a saturable induction process while no such evidence was forthcoming for Zn(II). In sub-line cells selected for tolerance to the highest concentrations of Cd(II) or Zn(II) isoMT formation was increased by another order of magnitude, reaching for some isoforms a 100- to 1000-fold augmentation over the amounts measured in cells of the unexposed parental cells. A potentiation of this magnitude goes beyond the range of ordinary regulation of gene expression. It is to be viewed instead as an enlargement of the capacity of isoMT synthesis acquired by a variety of mechanisms in the surviving cells. PMID- 8503894 TI - Rubredoxin oxidase, a new flavo-hemo-protein, is the site of oxygen reduction to water by the "strict anaerobe" Desulfovibrio gigas. AB - A rubredoxin-oxygen oxidoreductase, a homodimer with a molecular weight of 43 kDa per monomer, was found to be a component of an electron transfer chain that couples the reduction of oxygen to water with NADH oxidation. This FAD-containing protein appears to contain a new type of heme group. The electron transfer chain is not inhibited by cyanide and azide. In contrast, CO decreases NADH oxidation rate and also induces release of the prosthetic groups from the native terminal reductase. PMID- 8503895 TI - The primary structure of rat ribosomal protein S9. AB - The amino acid sequence of the rat 40S ribosomal subunit protein S9 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein S9 has 193 amino acids, the NH2-terminal methionine is removed after translation of the mRNA, and has a molecular weight of 22,360. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 14 to 16 copies of the S9 gene. The mRNA for the protein is about 1,000 nucleotides in length in part because of an especially long 5' noncoding region (103 nucleotides). Rat S9 is related to ribosomal proteins from other eukaryotes, Saccharomyces cerevisiae YS11 and Dictyostelium discoideum rp 1024, and to the eubacterial, archaebacterial, and chloroplast family of S4 ribosomal proteins. We have identified the product of the Trypanosoma brucei gene U as the homolog of rat ribosomal protein S9. PMID- 8503896 TI - A simple and reproducible method for analysis of chromatin condensation. AB - A method for examination of chromatin condensation with the help of gel electrophoresis in low-density agarose gels was suggested. This method provides a way for the degree of chromatin condensation to be estimated at different ionic conditions of the medium. It led to results which are in close agreement with the results of other traditional methods. Thus it was inferred that this method offers an alternative to the method of density-gradient ultracentrifugation for chromatin condensation study. PMID- 8503897 TI - Isolation of cDNAs encoding the catalytic domain of poly(ADP-ribose) polymerase from Xenopus laevis and cherry salmon using heterologous oligonucleotide consensus sequences. AB - We have isolated and sequenced cDNAs encoding the catalytic domain of poly(ADP ribose) polymerase (PARP) from Xenopus laevis and Oncorhyncus masou (cherry salmon). The cDNAs were amplified by polymerase chain reaction using heterologous oligonucleotides corresponding to the conserved sequences of mammalian cDNAs as primers. The deduced amino acid sequences of Xenopus laevis and cherry salmon cDNA showed 84.4% and 75.6% similarities to that of human PARP, respectively. In both species, mRNA for PARP was identified as a single band of 4 kb, and PARP mRNA was abundant in ovary and brain. Thus, mixed oligonucleotide-primed amplification is a useful method in the cloning of cDNAs from different species, and the catalytic domain of PARP is conserved structurally among phylogenetically different species, suggesting an importance of poly(ADP-ribosyl)ation. PMID- 8503898 TI - Phosphorylation of protein tau by double-stranded DNA-dependent protein kinase. AB - Alzheimer Disease (AD) is a distinct form of dementia characterized by the occurrence of neurofibrillary tangles, neurotic plaques and loss of certain neuronal populations. The tangles are associated with the presence of abnormal proteinaceous deposits. One such protein, referred to as tau, is found to be excessively phosphorylated in AD. We demonstrate that a double-stranded DNA stimulated protein kinase (referred to as DNA-PK) effectively catalyzes the phosphorylation of recombinant human protein tau. Moreover, in the presence of stimulatory DNA, the hyperphosphorylation of tau is accompanied by a significant shift in its mobility on SDS polyacrylamide gels. These results suggest that DNA PK may contribute to the pathogenesis of AD. PMID- 8503899 TI - Plasma glutathione peroxidase reduces phosphatidylcholine hydroperoxide. AB - The reducing activity of rat plasma glutathione peroxidase on phosphatidylcholine hydroperoxide (PC-OOH) and cholesteryl ester hydroperoxide (CE-OOH) was examined since these hydroperoxides are the major oxidation products of plasma. PC-OOH was reduced by the enzyme while CE-OOH was not. The reduction of PC-OOH by the enzyme ceased when all thiol was consumed, but the activity was recovered by the addition of glutathione, suggesting glutathione is important to keep the enzyme in the reduced form. These results are consistent with the findings that CE-OOH is present in human and rat plasmas while PC-OOH is undetectable and suggest that one of the physiological roles of the enzyme is to reduce PC-OOH. PMID- 8503900 TI - Nonamer binding protein induces a bend in the immunoglobulin gene recombinational signal sequence. AB - DNA bending has been shown to play a critical role in conservative site-specific DNA recombination reactions such as lambda integration. V(D)J recombination, the only mammalian site directed recombination system, is directed by recombinational signal sequences composed of heptamer, nonamer and spacer elements. The nonamer element, GGTTTTTGT, is similar to the consensus sequence for bent DNA. Using the circular permutation electrophoretic mobility assay, we show that the nonamer sequence has a detectable intrinsic bend. The nonamer sequence has been shown to be the binding site for nonamer binding protein (NBP). Binding of NBP to the nonamer site increases the apparent angle of the bend from 32 degrees to 66 degrees. The identification of a protein induced DNA bend near the site of V(D)J recombination may have implications for our understanding of the mechanism of V(D)J recombination. PMID- 8503901 TI - A fatal, systemic mitochondrial disease with decreased mitochondrial enzyme activities, abnormal ultrastructure of the mitochondria and deficiency of heat shock protein 60. AB - We report on a girl presenting with facial dysmorphic features and breathing difficulties upon birth. She was hypotonic, developed a metabolic acidosis, and died two days old of heart failure. Post-mortem examination revealed abnormalities of brain, lungs, heart and liver. In cultured skin fibroblasts activities of enzymes of oxidative phosphorylation, pyruvate metabolism, beta oxidation and other mitochondrial (mt) metabolic pathways were markedly decreased. Activities of enzymes localized in the mt outer membrane or in other cell organelles were found to be normal. The mitochondria appeared swollen and were located mainly around the nucleus. Electron micrographs showed locally disintegrated mt inner membranes and large mt vacuoles. The amount of mt heat shock protein 60 (hsp60) was about one fifth of that in controls. We conclude that this mt disorder is most likely caused by defective synthesis and maintenance of mitochondria, possibly due to a defect in mt protein import or enzyme assembly resulting from deficiency of hsp60. PMID- 8503902 TI - Expression of bovine seminal ribonuclease in Escherichia coli. AB - Bovine seminal RNAase (BS-RNAase), an unusually dimeric member of the pancreatic like ribonuclease superfamily, is also a multifunctional biological effector, with antitumor, immunosuppressive, and antispermatogenic activities. We report here the cloning of a semi-synthetic cDNA coding for the protein subunit chain, its expression with a T7 expression system in Escherichia coli inclusion bodies, the dimerization of correctly reoxidized monomeric protein, followed by the purification in high yields of the recombinant enzyme, and by its conversion to a protein undistinguishable from BS-RNAase as isolated from seminal vesicles, both in its catalytic activity and in the micro-heterogeneity of its quaternary structure. PMID- 8503903 TI - Differential modulation of fos and jun gene expression by 1,25-dihydroxyvitamin D3. AB - 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) modulates the mitogenic response to alpha thrombin either positively or negatively in vascular smooth muscle (VSM) cells depending upon the time at which cells are exposed to 1,25-(OH)2D3. We now examine the impact of 1,25-(OH)2D3 on the induction by alpha-thrombin of c-jun and c-fos mRNA. When 1,25-(OH)2D3 and alpha-thrombin were added simultaneously to rat VSM cells, c-jun expression was enhanced by five-fold compared to cells exposed to thrombin alone. However, when cells were exposed to 1,25-(OH)2D3 for 48h prior to thrombin, c-jun expression after alpha-thrombin was reduced to less than 25% of the level in cells exposed to thrombin alone. c-fos expression after alpha-thrombin was unaffected by 1,25-(OH)2D3. Thus 1,25-(OH)2D3 dramatically alters the ratio of jun/fos mRNA produced during the mitogenic response and may thus modulate the response to mitogens. PMID- 8503904 TI - Altered epidermal growth factor signal transduction in activated Ha-ras transformed human keratinocytes. AB - Epidermal growth factor (EGF) can stimulate proliferation and 92 kDa gelatinase/matrix metalloproteinase (MMP-9) expression. The induction of MMP-9 is not only pathologically significant for invasion and metastasis, but also serves as a semiquantitative measure of EGF signal transduction. In order to examine the role of mutated ras p21 in EGF signal transduction, an activated Ha-ras transformed human keratinocyte cell line was developed and characterized. Overexpression of the mutated Ha-ras p21 in these cells was demonstrated. Our results showed that EGF induced 92 kDa MMP-9 secretion was doubled in the ras transformed keratinocytes in comparison to the parent cells. The karyotype, the expression of EGF receptor (EGFR) and transforming growth factor (TGF) alpha at the mRNA level remained unchanged. These results suggest that the presence of high levels of mutated ras p21 may be responsible for the aberrant EGF signal transduction and contributes to transformation. In addition, a reduction of TGF beta expression at mRNA level by 70% was found in the activated Ha-ras transformed keratinocytes when compared to the parent cells. PMID- 8503905 TI - Isolation and characterization of the gene encoding rat glucose-dependent insulinotropic peptide. AB - The rat glucose-dependent insulinotropic peptide (GIP) gene has been isolated and characterized. The gene spans approximately 8.2 kilobase pairs (kb) and the GIP mRNA (0.8 kb) is encoded by six exons. The 42 amino acid hormone is encoded by exons 3 and 4. The exon-intron organization of the rat GIP gene revealed that the splice acceptor site for intron 2 is 24 nucleotides downstream compared to the comparable splice acceptor site in the human gene. This intron sliding results in an 8 amino acid deletion in the amino terminal extension of the prepropeptide. Primer extension analysis and RNase protection assay demonstrated the existence of multiple closely spaced sites for transcriptional initiation. Both the 5' flanking region and intron 1 contain TATA and CCAAT boxes consistent with initiation of gene transcription, although a TATA box in intron 1 is functionally inactive in adult rats in spite of its reasonable location. PMID- 8503906 TI - The protein kinase inhibitor staurosporine induces morphological changes typical of apoptosis in MOLT-4 cells without concomitant DNA fragmentation. AB - The protein kinase inhibitor staurosporine induces ultrastructural changes typical of apoptotic cell death in MOLT-4 cells in a concentration range of 10 200 nM. The well known chromatin margination was indeed present, followed by characteristic nuclear protrusions. The formation of numerous homogeneously electron dense micronuclei was the final step of the process. Nevertheless we did not detect the distinctive internucleosomal DNA fragmentation which has been demonstrated to occur in a variety of cells exposed to agents causing apoptosis. Our results strengthen recent argument showing that DNA breakage cannot be considered the sole criterion for detection of apoptosis. PMID- 8503907 TI - Expression of RAD4 gene of Saccharomyces cerevisiae that can be propagated in Escherichia coli without inactivation. AB - The RAD4 gene of Saccharomyces cerevisiae, which is essential for the nucleotide excision repair, was isolated from a yeast genomic library and the expression of this gene has been investigated. RAD4 mRNA was approximately 2.3 kb and di not contain intervening sequence, as determined by S1 nuclease mapping and Northern blot analysis. Transcription start site was located at 48 bp upstream of the ATG initiation codon. RAD4 gene is not induced by UV light damages as indicated by the absence of change in mRNA level after UV exposure in wild type yeast cells. The size of Rad4 protein overexpressed in Escherichia coli was found to be 89 kDa by SDS-PAGE. This is consistent with the size of the gene's ORF, which encodes 730 amino acids with the calculated molecular weight of 84456. The RAD4 protein contains many potential kinase dependent phosphorylation sites and its C-terminus is highly acidic like other DNA repair proteins of S. cerevisiae. PMID- 8503908 TI - NGF level of is not decreased in the serum, brain-spinal fluid, hippocampus, or parietal cortex of individuals with Alzheimer's disease. AB - Although the cause of Alzheimer's disease (AD) is unknown, nerve growth factor (NGF) has gained attention as a therapeutic agent for the disease. Because NGF maintains the magnocellular cholinergic neurons that are damaged in AD, research interests have been focused on the change in NGF level in patients with AD. This is the first reported study in which human NGF levels were accurately measured and compared between normal and AD samples. We measured NGF levels using enzyme immunoassay (EIA) system for human NGF and found no difference in NGF level in serum, brain-spinal fluid, or brain (hippocampus and parietal cortex) obtained from normal people and patients with AD. These results suggest that a decrease in the NGF level is not a causative factor of AD. PMID- 8503909 TI - Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor. AB - Through binding to cholecystokinin (CCK) A receptors, CCK is an important physiologic regulator of both gallbladder contraction and pancreatic enzyme secretion. In this work, we have used a combination of hybridization screening of a cDNA library and polymerase chain reaction to clone a 2.1 kb cDNA which encodes the human gallbladder CCKA receptor. Nucleotide sequence analysis revealed an open reading frame encoding a 428 amino acid protein, with seven putative transmembrane domains and a high degree of homology with the rat CCKA receptor. COS cells transfected with this cDNA clone bound CCK-8 and L-364,718 with high affinities appropriate for the CCKA receptor, and exhibited a transient increase in intracellular calcium in response to CCK. This should provide an important resource for the analysis of the role of this receptor in human physiology and pathophysiology. PMID- 8503910 TI - The salvage of deoxycytidine into dCDP-diacylglycerol by macrophages and lymphocytes. AB - Extracellular deoxycytidine (CdR) was previously shown to be salvaged into water soluble [1] and also into lipidic [2] precursors of phospholipids in stimulated lymphocytes and in lymphoma cells [3]. In this paper we have described that non dividing murine macrophages salvaged not only 5-3H-CdR but also tritiated thymidine (3H-TdR) mainly into the pools as nucleotides. Chlorpromazine shifted the CdR salvage into a lipidic compound of the cells which was identified as 3H dCDP-diacylglycerol (dCDP-DAG). After 5-3H-CdR labeling the lipid/DNA ratio was eleven times higher in macrophages than in tonsillar lymphocytes. Thin layer chromatography (TLC) on borate impregnated silica gel plates gave clear separation of CDP-DAG from dCDP-DAG supporting that the extracellular precursor for it is exclusively deoxycytidine and not ribocytidine. No interconversion between deoxy- and and ribocytidine could be observed neither in lymphocytes nor in macrophages. PMID- 8503911 TI - Role of delta-PKC on the differentiation process of murine erythroleukemia cells. AB - In murine erythroleukemia (MEL) cells the length of the latent period before the onset of hexamethylenebisacetamide induced terminal erythroid differentiation is inversely correlated to the intracellular level of delta-PKC. This is supported by the following experimental evidence. V3.17[44] MEL cell line, characterized by a very high rate of differentiation, contains an amount of delta-PKC protein one third lower than that present in the N23 MEL cell line, characterized by a very low rate of differentiation. A similar difference in the amount of delta-PKC mRNA is present in the two cell lines. In N23 cells, following addition of HMBA, the amount of delta-PKC protein and delta-PKC mRNA is down-regulated to one third its original value, which now corresponds to that constitutively present in V3.17[44] cells. Furthermore, in these cells the levels of delta-PKC protein and of its specific mRNA are unaffected by treatment with HMBA. Following introduction of homologous purified delta-PKC both MEL cell variants display a longer latent period before the onset of differentiation from 50 to 75 hours in N23 cell line and from 20 to 40 hours in V3.17[44] cells, respectively. Taken together, these results suggest that a delta-PKC related signal plays a negative role in the early stages of MEL cell differentiation and that the level of the kinase is controlled through a down-regulation process upon exposure to the chemical inducer. PMID- 8503912 TI - Sec-Y protein is localized in both the cytoplasmic and thylakoid membranes in the cyanobacterium Synechococcus PCC7942. AB - Members of the SecY protein family mediate protein export in bacterial cells. Southern analyses showed that secY is likely a single copy gene in the cyanobacterium Synechococcus PCC7942. Then the subcellular location of the cyanobacterial SecY protein was determined; i) antiserum raised against a fusion protein between the SecY fragment and maltose binding protein were used for immunoblotting of the membrane fractions, and ii) a modified SecY protein carrying the c-Myc peptide tag was expressed in the cyanobacterial cells, and the subcellular distribution of the SecY-c-Myc fusion protein was analyzed with the anti-c-Myc antibodies. The obtained results suggest that the SecY protein is localized in the thylakoid membrane as well as the cytoplasmic membrane; the SecY protein probably mediates protein translocation across both the cytoplasmic and thylakoid membranes in Synechococcus PCC7942. PMID- 8503913 TI - Expression of bone morphogenic protein 7 mRNA in MDCK cells. AB - Recently, a family of proteins, bone morphogenic proteins (BMPs), have been identified, which promote osteoblast differentiation and bone mineralization. One of them, BMP7, has been shown to be expressed at high levels in the kidney. We detected the message in a kidney tubular cell line, Madin-Darby canine kidney (MDCK) cells. After serum starved for 48h, 8-bromo-cAMP enhanced BMP7 mRNA at 3h and forskolin enhanced it at 6h to 24h in MDCK cells. PMA increased BMP7 mRNA at 6h but down-regulated it at 12h and 20h. The result suggests that BMP7 gene expression may be regulated in MDCK cells by PKA and PKC. MDCK cells can be used in further studies of BMP7 regulation. PMID- 8503914 TI - Activation of ATP-sensitive K+ channels by cyclic AMP-dependent protein kinase in cultured smooth muscle cells of porcine coronary artery. AB - The effects of cyclic AMP-dependent protein kinase on ATP-sensitive K+ channels in cultured smooth muscle cells of the porcine coronary artery were investigated using the patch-clamp technique. Extracellular application of isoproterenol (1mM), a beta agonist, or forskolin (2 x 10(-5)M), an activator of adenylate cyclase, activated these channels in cell-attached patch configurations, which were not blocked by phorbol 12-myristate 13-acetate (10(-6)M), an activator of protein kinase C. Cyclic AMP-dependent protein kinase activated these channels in inside-out patch configurations. These results suggest that cyclic AMP-dependent phosphorylation modulates ATP-sensitive K+ channels, in addition to its well known effects on Ca(2+)-activated K+ channels. The activation of ATP-sensitive K+ channels by cyclic AMP-dependent phosphorylation contributes to hyperpolarization of the membrane and to the relaxation of vascular smooth muscle cells. PMID- 8503915 TI - Phosphorylation of cardiac myosin light chain 2 by protein kinase C and myosin light chain kinase increases Ca(2+)-stimulated actomyosin MgATPase activity. AB - Myosin light chain 2 (MLC2) phosphorylation in rat cardiac whole myosin by cardiac myosin light chain kinase (MLCK) or by protein kinase C (PKC) resulted in increased actin-stimulated myosin MgATPase activity. The phosphorylation also increased Ca(2+)-stimulated myofibrillar MgATPase activity upon substitution of the phosphorylated myosin into myofibrils. In addition, phosphorylation of MLC2 in myofibrils by MLCK increased both the Ca(2+)-sensitivity and maximum activity of the myofibrillar Ca(2+)-stimulated MgATPase activity. The latter effect was inhibited by PKC-phosphorylation of troponin I, troponin T and C-protein. A role for both PKC and MLCK in regulating cardiac myofibrillar activity, via phosphorylation of various contractile proteins, is indicated. PMID- 8503916 TI - A new pathway for the degradation of a sesquiterpene alcohol, nerolidol by Alcaligenes eutrophus. AB - An oxidative pathway hitherto unknown for the degradation of a sesquiterpene alcohol, nerolidol (I) by Alcaligenes eutrophus is presented. Fermentation of nerolidol (I) by this organism in a mineral salts medium resulted in the formation of geranylacetone (II) and an optically active alcohol (S)-(+) geranylacetol (III), as major metabolites. Nerolidol (I) induced cells readily transformed 1,2-epoxynerolidol (IV) and 1,2-dihydroxynerolidol (V) into geranylacetone (II). These cells also exhibited their ability to carry out stereospecific reduction of II into (S)-(+)-geranylacetol (III). Oxygen uptake studies clearly indicated that nerolidol induced cells oxidized compounds II, III, IV, V and ethyleneglycol. Based on these observations a new oxidative pathway for the degradation of I is suggested which envisages the epoxidation of the terminal double bond, opening of the epoxide and cleavage between C-2 and C-3 in a manner similar to the periodate oxidation of diol. PMID- 8503917 TI - Differential damage by hypoxia to dopamine and serotonin nerve terminals. AB - Serotonin and dopamine resemble each other in terms of their synthetic and degradative pathways, as well as in terms of structural features. However, responses to a low-oxygen environment differ between these two compounds. In this experiment, we studied the fluctuations of levels of serotonin, dopamine and their metabolites in the striatum of the rat brain under low-oxygen conditions using a microdialysis technique. Comparison of the extents of increases in extracellular levels of dopamine and serotonin, accompanied by decreases in levels of metabolites, indicates that the effects of hypoxia on the two types of neuronal terminal are different. This study suggests that dopamine plays a more important role than serotonin in the mechanism of irreversible destruction of neurons during moderate hypoxia. PMID- 8503918 TI - Inhibition of NF-kappa B activation by vitamin E derivatives. AB - Nuclear factor kappa B (NF-kappa B) is believed to play an important role in the activation of a human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS). Recent findings suggesting an involvement of reactive oxygen species in signal transduction pathways leading to NF-kappa B activation have ensured the possible clinical use of antioxidants in blocking HIV activation. The present study examined the effects of vitamin E derivatives on the tumor necrosis factor-alpha (TNF-alpha) induced NF-kappa B activation. Incubation of human Jurkat T cells with vitamin E acetate or alpha-tocopheryl succinate (10 microM to 1 mM) exhibited a concentration dependent inhibition of NF-kappa B activation. alpha-Tocopherol or succinate at these concentrations had no apparent effects. 2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC) was extremely effective, causing complete inhibition of NF-kappa B activation at 10 microM. Oct 1 binding activity was inactivated by alpha-tocopheryl succinate whereas other derivatives had no effects, suggesting that the effects of alpha-tocopheryl succinate are not specific to NF-kappa B. HPLC measurements demonstrated that treatment of cells with TNF-alpha had no effects on cellular alpha-tocopherol, but vitamin E acetate treatment increased the alpha-tocopherol content. Cell viability was not affected by any of the vitamin E derivatives. These results indicate a possible use of vitamin E derivatives in AIDS therapeutics. PMID- 8503919 TI - L-arginine inhibits balloon catheter-induced intimal hyperplasia. AB - Intimal hyperplasia that results from therapeutic revascularization is an important etiologic factor in the failure of these procedures (i.e., restenosis). Drugs which donate nitric oxide have been shown to inhibit the proliferation of vascular smooth muscle cells in vitro. We tested the hypothesis that administration of L-arginine (0.5 g/kg/day), the precursor of nitric oxide, would inhibit development of intimal hyperplasia following balloon catheter-induced injury. L-arginine administration from 2 days prior to and 2 weeks following catheter-induced injury to the rabbit thoracic aorta attenuated the development of intimal hyperplasia by 39% as compared with untreated controls. This effect was due to decreased intimal area. The effect of L-arginine was inhibited by co administration of an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (0.5 g/kg/day). These data demonstrate that L-arginine attenuates intimal hyperplasia and suggest that the mechanism for this effect is the conversion of L-arginine to nitric oxide. PMID- 8503920 TI - Effect of interleukin-11 on the levels of mRNAs encoding heme oxygenase and haptoglobin in human HepG2 hepatoma cells. AB - Effect of recombinant human interleukin-11 (rhIL-11) on the expression of transcripts encoding microsomal heme oxygenase (HO), the rate-limiting enzyme in heme catabolism, and haptoglobin (Hpt), a major acute-phase protein, were examined in human HepG2 hepatoma cells. Treatment of HepG2 cells with rhIL-11 elicited an increase in HO mRNA in a dose- and a time-dependent fashion. The dose response curve, its magnitude of response and its time course were similar to those observed with recombinant human interleukin-6 (rhIL-6). In contrast, rhIL 11 had a far smaller effect on the level of Hpt mRNA than did rhIL-6. These findings demonstrate that the two cytokines are similar in regulating heme catabolism, while markedly different in inducing certain acute-phase proteins. PMID- 8503921 TI - Recombination between human immunodeficiency viruses (HIV) type 1 and 2 results in generation of defective hybrid viruses. AB - Dual infection by HIV-1 and HIV-2 is already documented. To test if this could lead to recombination and generation of altered viruses, recombination between HIV-1 and HIV-2 DNAs was studied. Release of recombinant viruses was detected following cotransfection of human rhabdomyosarcoma cells with truncated versions of these proviral DNAs. Linearization of plasmid DNAs was required for virus production. Analysis of viral particles by hybridization revealed the presence of viral RNA. However viral replication was not evident. A computer search of the overlap region between the substrate DNAs revealed 66% homology despite an overall genomic sequence homology of only 35%. These data suggest possible generation of replication-deficient hybrid viruses as a result of recombination between HIV-1 and -2. PMID- 8503922 TI - Inhibition of serine proteinases belonging to the chymotrypsin superfamily by the cyclic thiolic compound YS3025: a comparative crystallographic study. AB - The synthetic cyclic thiolic compound 3-[2-(2-thiophencarboxythio)]-propanoyl-4 thiazolidin carboxylic acid (YS3025) acts as an effective inhibitor of bovine alpha-chymotrypsin. In the present communication YS3025 binding studies are extended to bovine beta-trypsin and porcine pancreatic elastase, by means of crystallographic difference Fourier techniques. For all the enzymes considered, the thiopencarbonyl moiety of YS3025 is located at the entrance of the inhibited proteinase primary specificity pocket (S1), covalently linked to the catalytic Ser195 OG atom, and forming an acyl-enzyme complex. These observations allow to select between alternative binding (and inhibition) mechanisms for YS3025 and related molecules to serine proteinases belonging to the chymotrypsin superfamily. PMID- 8503923 TI - In vitro DNA methylation inhibits FMR-1 promoter. AB - In fragile X syndrome, the FMR-1 gene is changed by a CGG repeat mutation and an abnormal methylation at a CpG-island 5' to the gene. To elicit if methylation itself inactivates the gene, FMR-1 promoter was defined by deletion mapping and primer extension assay and was analyzed by in vitro methylation. Promoter activity was measured by transient expression and chloramphenicol acetyl transferase assay. Although this promoter contains several HpaII sites, it was not affected by methylation with HpaII methylase. However, the promoter was completely repressed by methylation with M. SssI which methylates all cytosines of CpG dinucleotides. This repression could not be overridden by SV-40 enhancer. This study indicates that methylation could be the direct cause of FMR-1 inactivation in fragile X syndrome. PMID- 8503924 TI - Regulation of C-fos expression by sodium butyrate in the human colon carcinoma cell line Caco-2. AB - We used sodium butyrate to modify the differentiation and growth properties of the Caco-2 colon adenocarcinoma cell line and considered c-fos proto-oncogene expression as a potential target. C-fos is induced by butyric acid very rapidly at a post-transcriptional level and is stimulated transcriptionally at later times. This transcriptional induction does not result in an increase in steady state mRNA levels. We show by transient transfection assays that the ATF-CRE binding site located between -63 and -54 relative to the c-fos transcriptional start site is a target for butyrate-induced fos transcription. Furthermore, gel retardation assays show an increase in CRE binding activity in cells treated with butyrate. These results demonstrate that butyrate can affect specific transcription factors important for cell growth and differentiation at multiple levels of regulation. PMID- 8503925 TI - On the cytosolic and perinuclear mortalin: an insight by heat shock. AB - We have identified, cloned and characterized a 66-kD protein from cytosolic fractions of mouse embryonic fibroblasts and named it mortalin (Wadhwa et al., J. Biol. Chem., 268, in press, 1993). Immortal fibroblasts were seen to harbor the same or very similar protein, however, localized in the perinuclear locale. The present report is on the differentially localized forms of p66 protein which are biochemically and structurally found to be widely the same. In fact, heat shock treatment could translocate the cytosolic form to the perinuclear position without any detectable biochemical modification. The observed phenomenon adds to the unique identity of mortalin in hsp70 family. Besides, it confers that only the minor differences in the protein probably enroute its differential cellular distribution and the associated function. PMID- 8503926 TI - Cloning of the mouse interleukin 2 receptor gamma chain: demonstration of functional differences between the mouse and human receptors. AB - We isolated a cDNA clone for the gamma chain of the mouse interleukin 2 receptor. Introduction of the mouse gamma chain cDNA clone into a mouse fibroblast cell line, L929, expressing the mouse alpha beta heterodimer IL-2 receptor converted pseudo-high affinity of the IL-2 receptor into functional high, resulting in internalization of IL-2 and induction of the c-myc, c-fos and c-jun genes. The mouse beta gamma heterodimer, however, failed to bind IL-2 unlike the human beta gamma heterodimer intermediate-affinity receptor. These results indicate that the mouse functional IL-2 receptor is a complex comprising three distinct subunits, alpha, beta and gamma chains, but the beta gamma heterodimer is not functional and different from the human heterodimer. PMID- 8503927 TI - Production of monoclonal antibodies to prostromelysin (ProMMP-3) and establishment of a quantitative prostromelysin ELISA assay. AB - Human prostromelysin (59 kDa) was purified from the conditioned medium of IL-1 stimulated human dermal fibroblasts and anti-prostromelysin monoclonal antibodies were produced and identified by ELISA assay. Using prostromelysin, a C-terminally truncated recombinant form of prostromelysin consisting of amino acids 1-255, and their respective activated enzymes, we have begun mapping the epitopes recognized by these monoclonal antibodies. Various patterns of reactivity against the proenzymes and activated enzymes were observed. In further attempts to map the epitopes, we employed synthetic peptides representing hydrophilic regions of the primary amino acid sequence of prostromelysin. Our monoclonal antibodies did not recognize these peptides, suggesting that the antibodies may be recognizing conformational epitopes composed of non-linear portions of prostromelysin. Using these monoclonal antibodies, we have developed a quantitative prostromelysin sandwich ELISA assay. PMID- 8503928 TI - Phorbol esters induce insulin receptor phosphorylation in transfected fibroblasts without affecting tyrosine kinase activity. AB - The effects of phorbol ester induced activation of protein kinase C on insulin receptor phosphorylation and tyrosine kinase activity have been investigated in transfected fibroblasts expressing high levels of the human insulin receptor. Receptor phosphorylation was stimulated more than two-fold over basal levels upon treating CHO.T cells with PMA. This phosphorylation was additive with, rather than antagonistic to, that induced by insulin. Furthermore, PMA treatment was completely without effect on insulin-stimulated receptor tyrosine kinase activity. Similar results were obtained in NIH3T3 HIR3.5 and Rat 1 HIRc-B cells. It is concluded that the previously reported inhibitory effect of PMA on receptor kinase activity is not of general regulatory significance in all cell types. PMID- 8503929 TI - Availability of tetrahydrobiopterin is not a factor in the inability to detect nitric oxide production by human macrophages. AB - Human macrophages, in contrast to murine macrophages, do not produce nitric oxide after stimulation with cytokines. This failure has been attributed to the known lack of production by human macrophages of tetrahydrobiopterin, an essential cofactor for nitric oxide synthase. Increasing intracellular levels of tetrahydrobiopterin in cytokine-stimulated murine cells results in an increase in nitrite production. However, this treatment does not result in any detectable accumulation of nitrite by stimulated human monocyte-derived macrophages. Thus, the inability of these cells to produce nitric oxide appears to be unrelated to a lack of tetrahydrobiopterin and suggests that proper in vitro conditions may not yet have been discovered that permit nitric oxide synthesis by activated human macrophages. PMID- 8503930 TI - Suppressive effect of transforming growth factor-beta on the phosphorylation of endogenous substrates by conventional and novel protein kinase C in primary cultured mouse epidermal cells. AB - The effect of transforming growth factor-beta (TGF-beta) on the endogenous protein phosphorylation caused by phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), was examined in primary cultured mouse epidermal cells. PMA markedly stimulates phosphorylation of endogenous proteins, i.e. KP-1 and KP-2, through Ca(2+)-dependent conventional PKC (cPKC), and KP-10 through Ca(2+)-independent novel PKC (nPKC) in intact epidermal cells. TGF-beta strongly suppressed the PMA-stimulated phosphorylation of these three proteins. Rate of dephosphorylation of these phosphorylated proteins was not affected by TGF-beta. Treatment of epidermal cells with TGF-beta decreased cPKC activity both in cytosolic and particulate fractions, but not nPKC activity. These results indicate that TGF-beta suppresses cPKC- and nPKC-mediated endogenous protein phosphorylation in intact epidermal cells, but the mechanisms of suppression are different. PMID- 8503931 TI - Water-soluble chymotrypsin specific inhibitors containing arginine. AB - In an attempt to develop water-soluble, potent inhibitors for chymotrypsin, structurally rigid dipeptides containing arginine were designed and synthesized. The dipeptide H-D-Arg-Phe-NHBzl inhibited chymotrypsin very strongly (Ki = 5.9 microM). The dipeptide with the inverse sequence, H-D-Phe-Arg-NHBzl, was also a moderate inhibitor for chymotrypsin with Ki of 240 microM. In spite of the presence of arginine in these dipeptides, they inhibited trypsin only weakly, indicating that they are highly specific for chymotrypsin. High resolution 1H-NMR (400-MHz) indicated that these dipeptides can make a strong intramolecular hydrophobic interaction between Arg-beta, gamma, delta-methylenes and Phe-phenyl, producing a rigid hydrophobic core which interacts with the chymotrypsin S2 site. Since these dipeptides are easily soluble in water, they are regarded as the sophisticated and effective inhibitors for chymotrypsin. PMID- 8503932 TI - Changes in expression and CRE binding proteins of the fibronectin gene during aging of the rat. AB - The level of plasma fibronectin (pFNT) which is synthesized in the liver and secreted to the plasma has been found to decrease with age. Nuclear run-on transcription, slot-blot, and northern blot analysis also show that the expression of the FNT gene is lower in the liver of old rats. cAMP is known to influence the expression of the gene. Gel mobility shift assay using an oligonucleotide containing the cAMP responsive element (CRE) and nuclear extract of liver shows the presence of trans-acting factors that bind to CRE. These factors change with age. This may be the reason for the lower expression of the gene in the old rat. PMID- 8503933 TI - CRF provokes the release of norepinephrine by hemocytes of Viviparus ater (Gastropoda, Prosobranchia): further evidence in favour of the evolutionary hypothesis of the mobile immune-brain. AB - The concentration of biogenic amines (norepinephrine, epinephrine and dopamine) was determined by HPLC in serum and hemocytes of the mollusc Viviparus ater following in vitro incubation of the hemolymph with corticotropin-releasing factor (CRF) for different periods of time. CRF provoked the release of norepinephrine from hemocytes into the serum, the maximum level being observed after 15 min. incubation. Moreover, immunoreactive tyrosine hydroxylase and dopamine beta-hydroxylase, i.e., the enzymes involved in biogenic amine biosynthesis, have been demonstrated in hemocytes. These findings show that in invertebrates an ancestral type of stress response, similar to that performed by mammalian hypothalamic-pituitary-adrenal axis, occurs in phagocytic hemocytes, a cell type capable of both fundamental immune and neuroendocrine responses. PMID- 8503934 TI - Binding activity of the human transcription factor TFIID. AB - In order to investigate the conformational state of the human TFIID, we studied the structure of the TATA-box binding protein (TBP) which is the DNA-binding subunit of the transcription factor TFIID required for transcriptional initiation by RNA polymerase II. We showed that TBP was able to form dimers and tetramers by chemical crosslinking, subunit exchange, ultracentrifugation and gel shift experiment. These findings indicate that the TBP homodimers could be the inactive binding form of TFIID and therefore could explain the lack of Gal4-activated transcriptional activity of the E. coli-expressed human TBP. PMID- 8503935 TI - Nucleotide sequence of an abundant rice seed globulin: homology with the high molecular weight glutelins of wheat, rye and triticale. AB - A cDNA clone corresponding to a 19 kD salt-soluble globulin of rice (Oryza sativa L.) was isolated by screening a lambda gt11 expression library of endosperm mRNA with antibodies raised against the purified rice seed alpha-globulin. The cDNA contained a single large open reading frame encoding a putative globulin precursor of molecular weight of 21 kD. The polypeptide consists of 182 amino acids and is devoid of lysine residues. Computer analysis of the NH2-terminal sequence of the globulin precursor protein indicated the presence of an 18 amino acid signal peptide. Segments of the amino acid sequence of the rice globulin were homologous with sequences in high molecular weight glutelins of wheat. Antibodies specific for rice seed globulin also cross-reacted with seed proteins from wheat, rye and triticale. PMID- 8503937 TI - Suppression in mitochondrial electron transport is the prime cause behind stress induced proline accumulation. AB - Exposure of six day old rice (Oryza sativa) seedlings to salt or cadmium stress lead to an increase in the level of proline with a simultaneous decline in the mitochondrial electron transport activity. Mitochondrial electron transport inhibitors - rotenone, antimycin A or potassium cyanide also stimulated proline accumulation in rice seedlings with a concurrent decline in the mitochondrial electron transport activity. Four to five fold enhancement in proline level was noted in seedlings after 48 h exposure to electron transport inhibitors. A significant rise in the level of NADH was also noted in seedlings exposed to salt stress, cadmium stress or any of the electron transport inhibitors. These results show for the first time that the suppression in the mitochondrial electron transport activity lead to proline accumulation. Our results also suggest that the increase in the ratio of NADH to NAD+ due to the suppression in mitochondrial electron transport might be the prime reason behind proline accumulation in plants exposed to environmental stresses. PMID- 8503936 TI - Extrahepatic, differential expression of four classes of human alcohol dehydrogenase. AB - The amounts of mRNA expressed for different alcohol dehydrogenase (ADH) classes were determined in human tissues by Northern hybridization. ADH classes I, II, and III were expressed in all tissues. The mRNAs were highest for class I ADHs, with particularly strong signals in liver, lung, ileum, colon, and uterus. For class II ADH, such a wide tissue distribution had not been recognized previously. Expression of class III ADH was highest in testis, followed by uterus, colon, and ileum. The amounts of class I and III ADH mRNAs varied significantly, indicating that tissue-specific factors modulate the expression of these enzymes above a basal level. Class V ADH (ADH6) was not detected in any of the tissues, including stomach. This suggests that class V ADH is not identical with human stomach sigma ADH (class IV). The results support the general proposition that ADHs are not restricted to liver and have functions other than those in ethanol oxidation. PMID- 8503938 TI - Effects of endothelin-1 on bovine parathyroid cells. AB - Endothelin-1 (ET-1) is synthesized and released by parathyroid epithelium. The effects of endothelin isopeptides were studied in clonal bovine parathyroid endothelial (BPE) cells. BPE cells did not produce ET-1, but showed ETA receptors (Kd = 0.1 +/- 0.02 nM, mean +/- SE). ET-1 (10(-8)10(-11)M) increased the intracellular calcium ion concentration ([Ca2+]i) in BPE cells, while endothelin 3 (ET-3) was ineffective. The increase in [Ca2+]i was less sustained in the absence of extracellular Ca2+ ions. Moreover ET-1 induced phospholipase C (PLC) activation, as demonstrated by the increase in inositol trisphosphate. Cell growth was not affected by ET-1 in a wide range of concentrations. The present findings demonstrate: 1) BPE cells possess ETA receptors; 2) the peptide activates PLC and increases cytosolic [Ca2+]i via both a release of Ca2+ ions from intracellular calcium pool(s) and an influx of the cation from the extracellular milieu. A possible role of ET-1 as a paracrine factor in parathyroid tissue can be hypothesized. PMID- 8503939 TI - Ins(1,4,5)P3 and glutathione increase the passive Ca2+ leak in permeabilized A7r5 cells. AB - Thapsigargin depletes intracellular Ca2+ stores by its inhibitory effect on the Ca2+ pumps, which unmasks an aspecific Ca2+ leak from the stores. This aspecific Ca2+ permeability of the stores was further investigated using 45Ca2+ fluxes on intact and permeabilized A7r5 smooth-muscle cells. Stores in intact cells were found to be more leaky for Ca2+ than those in saponin-permeabilized or Staphylococcus aureus alpha-toxin-permeabilized cells, which suggests that a cytosolic factor may be involved. Supplementing the medium bathing the permeabilized cells with a submaximal Ins(1,4,5)P3 concentration increased the leakiness of the stores. Glutathione also increased the aspecific Ca2+ leak. This effect occurred with both the reduced and the oxidized form but reduced glutathione was more effective. Our data show that basal Ins(1,4,5)P3 levels and glutathione can contribute to the relatively high Ca2+ leak in intact cells. The washing out of these substances during permeabilization can reduce the aspecific leakiness of the stores. PMID- 8503940 TI - Isolation and characterization of (+)-1,1a-dihydroxy-1-hydrofluoren-9-one formed by angular dioxygenation in the bacterial catabolism of fluorene. AB - Transformation of fluorene by washed cells of fluorene-grown Pseudomonas sp. F274 yielded 1,la-dihydroxy-1-hydrofluoren-9-one (up to 100 mg/l) as the stable product of angular dioxygenation of 9-fluorenone. Structural identity of the angular keto-diol was established by 13C- and 1H-NMR, gas chromatography- and direct probe-mass spectrometry. Definitive assignment of 1,1a-dioxygenation, but not 4,4a-, was based on the isolation and rigorous identification of 1 hydroxyfluoren-9-one as the exclusive product of acidic dehydration. Chiral 1H NMR analysis and optical rotation of isolated 1,1a-dihydroxy-1-hydrofluoren-9-one ([alpha]D = + 132.1 degrees) are indicative of a single enantiomer with an inferred cis-stereochemistry of the hydroxyl groups. This compound is evidently an intermediate of fluorene catabolism by this strain and not a dead-end product because its formation is transient in washed cell incubations and ultimately it is completely consumed with the formation of acidic metabolites. PMID- 8503941 TI - c-fos m-RNA expression after treatment with fetal bovine serum and epidermal growth factor for osteoblastic MC3T3-E1 cells cultured in a low calcium environment. AB - This paper examines the existence of c-fos mRNA expression in osteoblastic MC3T3 E1 cells cultured in a low calcium environment. The MC3T3-E1 cells were placed in a serum free medium for 24 hours after subconfluence and then the cells were treated with fetal bovine serum and epidermal growth factor for 0, 5, 10, 15, 30, or 60 minutes. The c-fos m-RNA expression was found in the MC3T3-E1 cells cultured in both normal medium (control group) and low Ca medium (low Ca groups). The degree of expression was significantly higher in the low Ca group than in the control group in each treatment period (p < 0.01) and in both groups, after the treatment with FBS or EGF, the expression levels increased with time at 5 and 10 minutes but decreased at 15 minutes. Thereafter, levels increased again to reach to a maximum at 30 minutes after which it decreased rapidly. On the other hand, in both groups, after the treatment with EGF, the expression increased at 30 minute. This suggests that the MC3T3-E1 cells placed in a low calcium environment react to restore cell functioning to normal at the gene level. PMID- 8503942 TI - The activities of coenzyme Q10 and vitamin B6 for immune responses. AB - Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4-lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4 lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer. PMID- 8503943 TI - The atherogenic potential of carbon monoxide. AB - This paper reviews the available evidence concerning the atherogenic potential of carbon monoxide. The evidence comes from two different types of studies- epidemiology studies on populations of humans chronically exposed to carbon monoxide, and animal studies conducted under conditions of controlled exposure to carbon monoxide. Data from both epidemiology and animal studies suggest that carbon monoxide is not atherogenic. Therefore, the increased levels of atherosclerosis associated with smoking as reported in epidemiology studies of human smokers probably cannot be attributed to CO exposure. PMID- 8503944 TI - Relations of sodium-lithium countertransport kinetics to plasma and red cell membrane phospholipids in hyperlipidemia. AB - As compared to 7 normolipidemic donors, the maximal velocity of sodium-lithium countertransport was accelerated by nearly 70% in 10 patients with elevated levels of triglyceride-rich lipoproteins and tended to be stimulated also in 5 patients with hypercholesterolemia. No significant differences were observed between normolipidemia and both hyperlipidemic groups for the apparent affinities of the transport system for intracellular sodium and extracellular lithium. Strong positive relations of the maximal activity of sodium-lithium countertransport to the percentages of red cell membrane phosphatidylcholine (r = 0.85, 2P < 0.001), the phosphatidylcholine/sphingomyelin (r = 0.82, 2P < 0.001) and the phosphatidylcholine/phosphatidylethanolamine ratio (r = 0.81, 2P < 0.001) were seen in all donors. A negative correlation was found to membrane sphingomyelin (r = -0.72, 2P < 0.001). Also plasma phosphatidylcholine and sphingomyelin exhibited positive and negative associations, respectively, to the maximal activity of sodium-lithium countertransport (r = 0.66, 2P < 0.01 and r = 0.78, 2P < 0.001). Among several plasma lipoprotein parameters investigated, total triglycerides or VLDL cholesterol levels showed independent relations to both the plasma and the membrane phosphatidylcholine/sphingomyelin ratio as well as to the maximal velocity of sodium-lithium countertransport. The results indicate that an increase in red cell membrane phosphatidylcholine and a concomitant fall in sphingomyelin are closely associated with the acceleration of sodium-lithium countertransport in hyperlipidemia. PMID- 8503946 TI - Inhibition of acyl-CoA cholesterol O-acyltransferase reduces the cholesteryl ester enrichment of atherosclerotic lesions in the Yucatan micropig. AB - Atherosclerotic lesion development may be altered indirectly by regulating plasma cholesterol or directly by inhibition of acyl-CoA cholesterol O-acyltransferase (ACAT) within cells of the artery. Yucatan micropigs were meal-fed a 2% cholesterol, 8% peanut oil, 8% coconut oil purified diet for 1 month prior to administration of the potent, bioavailable ACAT inhibitor CI-976, and induction of atherosclerotic lesions by chronic endothelial damage. After 84-108 days of therapy, CI-976 decreased mean plasma VLDL-cholesterol 85-91% and cumulative VLDL exposure (area under VLDL-time curve) by 65%. However, overall plasma total, LDL and HDL cholesterol and triglyceride levels were unchanged. CI-976 decreased liver cholesteryl ester (CE) content 65% without significantly affecting adrenal CE content. The CE content of the injured left femoral, left iliac and abdominal aorta and uninjured right femoral and iliac arteries and thoracic aorta was reduced 62-78% by CI-976. Systemic plasma CI-976 levels measured 24 h post-dose ranged from 2.26 to 4.05 micrograms/ml and significantly correlated with the reduction in both VLDL and vessel CE content. Thus, we conclude that inhibition of ACAT can blunt the cholesteryl ester enrichment of developing atherosclerotic lesions by preventing reesterification and storage of lipoprotein cholesterol within vascular cells and by reducing the plasma level and delivery to the arterial wall of such atherogenic lipoproteins as VLDL. PMID- 8503945 TI - Atherosclerosis in a rhesus monkey with genetic hypercholesterolemia and elevated plasma Lp(a). AB - A female rhesus monkey with a marked elevation of total plasma cholesterol LDL and Lp(a) while on a low-fat, low-cholesterol diet, died at 22 years of age. Her spontaneous hypercholesterolemia was related to a genetically determined LDL receptor deficiency (Scanu, A.M. et al., J. Lipid Res., 29 (1988) 1671). Autopsy revealed grossly visible multifocal to diffuse raised yellow plaques predominantly in the aorta and, to a lesser extent, in the coronary arteries. Microscopically, the plaques in the aorta and in the coronary arteries showed heavy lipid deposition. Some had features seen in advanced human atherosclerotic plaques, including a fibrous cap and a necrotic core. Immunohistochemical staining showed a co-localization of apo(a) with apo B in lesion sites, a pattern seen frequently in advanced human atherosclerotic plaques. Evidence of fibrinogen/fibrin in the plaque areas was also seen, but was not co-localised with either Lp(a) or apo B. This monkey developed progressive atherosclerosis which was not induced by diet, but rather was dependent on the LDL receptor deficiency with a possible contribution by the elevated plasma levels of Lp(a). PMID- 8503947 TI - Fatty acid composition in total phospholipids of human coronary arteries in sudden cardiac death. AB - A study was made of the fatty acid composition of the total phospholipid fraction of human coronary arteries in 30 cases of sudden cardiac death due to ischaemic heart disease (aged 40 +/- 5 years, mean +/- S.D.) and in 29 controls (mostly traffic accident victims, aged 45 +/- 6 years). The coronary arteries from cases of sudden cardiac death showed more atherosclerotic lesions than those of controls (P < 0.001). The percentages of palmitic acid (16:0) and linoleic acid (18:2(n-6)) were significantly higher and the percentage of arachidonic acid (20:4(n-6)) and of all the other major polyunsaturated fatty acids, both n-6 and n-3, was significantly lower in cases of sudden cardiac death than in controls. In conclusion, this study showed increased percentages of saturated and reduced percentages of polyunsaturated fatty acids, except linoleic acid, in total phospholipids of human coronary arteries in cases of sudden cardiac death. The results suggest an impaired metabolism of linoleic acid, possibly due to a decreased delta-6-desaturase activity in the coronary artery wall in cases of sudden cardiac death. PMID- 8503948 TI - Effects of doxazosin on atherosclerosis in cholesterol-fed rabbits. AB - Doxazosin was administered to rabbits fed diets enriched in cholesterol and peanut oil for 7.5 or 12 weeks, in 2 separate experiments. Doxazosin suppressed the accumulation of cholesterol and formation of atherosclerotic plaques in the aortas of treated rabbits and prevented a diet-induced increase in aortic collagen and wall mass. Doxazosin was more effective in the thoracic and abdominal segments of the aorta than in the aortic arch. Pharmacokinetic analysis indicated that treated rabbits were exposed to concentrations of doxazosin, integrated over 24 h, which were consistent with the therapeutic range of doxazosin measured in patients treated for hypertension. Doxazosin did not alter serum levels of cholesterol or triglycerides, nor were there any consistent effects on glucose, free fatty acid or ketone levels. Hypotheses of the mechanism of action of doxazosin are discussed, including the possible involvement of alpha 1-adrenergic receptors in recruitment of smooth muscle cells by subintimal macrophages and nonadrenergic mechanisms of inhibition of lipid infiltration. PMID- 8503949 TI - Protective effect of 17 beta-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells. AB - The ability of 17 beta-estradiol, progesterone, testosterone and cholesterol in preventing the cytotoxicity of oxidized LDL to cultured aortic bovine endothelial cells (BAEC) was tested and compared. The lipid peroxidation of LDL, promoted either by UV-C radiation, copper ions or cultured human lymphoblastoid cells, was inhibited in a dose-dependent manner by 17 beta-estradiol (IC50 were evaluated at around 50 +/- 10 mumol/l with UV on copper and 6 +/- 2 mumol/l with cells), whereas exogenous cholesterol, progesterone or testosterone were completely inactive under the range of concentrations tested (up to 100 mumol/l). Subsequently, this antioxidant effect of 17 beta-estradiol preventing LDL oxidation protected 'indirectly' BAEC against the cytotoxicity of oxidized LDL. 17 beta-Estradiol was also able to protect 'directly' BAEC against the cytotoxic effect of oxidized LDL (with an IC50 around 0.5 +/- 0.1 mumol/l), whereas the other steroids tested were almost completely inactive. This direct protective effect resulted from an increased resistance of BAEC against the cytotoxic effect of oxidized LDL as shown by pre-incubation of BAEC with 17 beta-estradiol. The protective effect of 17 beta-estradiol was present for 2-3 days. In conclusion, 17 beta-estradiol exhibited an antioxidant activity and was effective in protecting BAEC against the cytotoxicity of oxidized LDL by acting at two separate sites: (i) outside the cells, by inhibiting the LDL oxidation; (ii) inside the cells by increasing the cellular resistance against the cytotoxic effect of oxidized LDL. The potential relevance of these results in relation to prevention of atherogenesis is discussed. PMID- 8503950 TI - Simvastatin-induced decrease in the transfer of cholesterol esters from high density lipoproteins to very low and low density lipoproteins in normolipidemic subjects. AB - Hyperlipidemic patients often have an accelerated esterified cholesterol transfer (ECT) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL). We investigated the effect of simvastatin on ECT in twelve normolipidemic subjects. After 6 weeks of simvastatin administration, ECT was decreased by 23%. To determine the mechanism of action of simvastatin, we measured ECT in different recombination experiments, using an isotopic assay in which the transfer of labelled EC from HDL to VLDL/LDL was determined. When HDL of the treated subjects were incubated with VLDL/LDL and CETP fractions isolated from control plasma, no effect of simvastatin was observed, indicating that the drug did not alter the HDL-dependent ECT. This might be expected since simvastatin induced only minor modifications of HDL structure. When HDL and VLDL/LDL of control plasma were incubated with CETP fractions of the treated subjects, a clear reduction of ECT occurred after simvastatin administration. The decrease of plasma transfer activity was correlated to that of CETP concentration and accounted for the simvastatin-induced lowering of ECT. The diminution of plasma CETP was correlated to that of the apo B-containing lipoproteins concentration. This finding confirms previous reports suggesting a relationship between LDL level and CETP activity. In conclusion, our work shows that simvastatin administration results in a decrease of ECT and that this effect occurs through a lowering of plasma CETP activity. PMID- 8503952 TI - High-density lipoprotein reduces epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells. AB - High concentrations of high-density lipoprotein (HDL) are known to decrease the risk of coronary artery disease. In order to study the underlying cellular mechanisms, the influence of HDL on the epidermal growth factor (EGF)-induced vascular smooth muscle cell (VSMC) proliferation was investigated. Approximately 40% of the EGF-induced increase of the cell DNA synthesis was abolished in the presence of 30 micrograms/ml HDL. The EGF-induced dose-dependent (10 pg/ml to 100 ng/ml) increase in DNA synthesis was blunted by 30 micrograms/ml HDL. In addition HDL (3-300 micrograms/ml) caused a dose-dependent inhibition of EGF (20 ng/ml) induced DNA synthesis, yielding a half maximal effective dose (ED50) of 30 micrograms/ml. Similar experiments with the HDL-protein and HDL-lipid fraction indicated that the HDL-protein fraction is most probably responsible for the observed inhibiting effects of HDL. This was confirmed by using purified apolipoprotein (apo) A-I and apo A-II. Both induced an approximately 80% inhibition of the EGF-induced DNA synthesis. These results may help to explain the observed beneficial effects of HDL on cardiovascular diseases that are described in many epidemiological studies. PMID- 8503951 TI - Cytokine regulation of granulocyte-macrophage colony stimulating factor and macrophage colony-stimulating factor production in human arterial smooth muscle cells. AB - Smooth muscle cells (SMC) are the major cell type found in the walls of large blood vessels and appear to participate in local immune and inflammatory reactions, as well as in certain vascular diseases. We tested whether human arterial SMC can produce in vitro the colony stimulating factors (CSFs), granulocyte macrophage-CSF (GM-CSF) and macrophage CSF (M-CSF). Untreated internal mammary artery and aortic SMC produced no detectable GM-CSF but constitutively made M-CSF, measured by ELISA and radioimmunoassay, respectively. Interleukin-1 (IL-1) and, to a lesser extent, tumor necrosis factor alpha (TNF alpha) stimulated GM-CSF formation within 3 h; mRNA levels also increased particularly in the presence of the protein synthesis inhibitor, cycloheximide. IL-1, TNF alpha and, in addition, interferon-gamma (IFN-gamma) raised the M-CSF levels within 6 h; cycloheximide potentiated the effects of IL-1 and TNF alpha on mRNA levels. These results suggest that cytokine-stimulated human arterial SMC may be a source of the M-CSF found in atherosclerotic lesions. Since monocytes/macrophages can be activated by GM-CSF and M-CSF, while GM-CSF can also affect granulocyte function, SMC may participate in inflammatory reactions and vascular diseases by releasing these cytokines. PMID- 8503953 TI - Rare apolipoprotein E variant identified in a patient with type III hyperlipidaemia. AB - We report a rare apolipoprotein E variant in an Irish female with Type III hyperlipidaemia who has the phenotype E2E1 as determined by isoelectric focusing. Sequence analysis of the apolipoprotein E gene from the proband and from four other family members, using DNA amplified by the polymerase chain reaction, demonstrated the presence of a point mutation in the common epsilon 2 allele with a G-->A transition at nucleotide 3791. This was confirmed by digestion with the restriction endonuclease TaqI, which cuts at a new site within the apolipoprotein E gene, created by the base change. This mutation results in a substitution of aspartic acid for glycine at position 127 of the mature protein. We believe this to be the first description of this apolipoprotein E variant in a family from the British Isles. The mutation appears to be 'recessive' with respect to the expression of Type III hyperlipidaemia, although it may be somewhat more potent in this regard than the parent epsilon 2 allele. The Type III hyperlipidaemia is responsive to treatment with diet and gemfibrozil. PMID- 8503955 TI - A computer-aided method of measuring nasal symmetry in the cleft lip nose. AB - Objective assessment of the results of cleft lip and nose surgery is necessary to quantify differences between alternative surgical techniques. A previously described method of measuring facial asymmetry has been modified to allow a comparison of differently treated cleft noses (radical nasal correction versus no nasal correction). Standardised, inferior view photographs of 10-year-olds were obtained from patient records. These were projected, traced, digitised and analysed using a BBC microcomputer. A method of excluding the ill-defined nasal baseline by obtaining a mirror-image of the upper nasal perimeter is described. The method has a high degree of inter and intra observer reproducibility. PMID- 8503954 TI - Mutants in disulfide bond formation that disrupt flagellar assembly in Escherichia coli. AB - We report the isolation and characterization of Escherichia coli mutants (dsbB) that fail to assemble functional flagella unless cystine is present. Flagellar basal bodies obtained from these mutants are missing the L and P rings. This defect in assembly appears to result from an inability to form a disulfide bond in the P-ring protein (FlgI). Cystine suppresses this defect in dsbB strains. We also show that dsbA strains [Bardwell, J. C. A., McGovern, K. & Beckwith, J. (1991) Cell 67, 581-589] fail to assemble P rings, apparently from a similar failure in disulfide bond formation. However, cystine does not completely suppress this defect in dsbA strains. Thus, disulfide bond formation in FlgI is essential for assembly. DsbA likely puts in that bond directly, whereas the DsbB product(s) play a role in oxidizing DsbA, so that it can be active. PMID- 8503956 TI - [The computer-aided development of orthodontic treatment elements made from NiTi memory alloys exemplified by a pseudoelastic retraction spring]. AB - Employing the segmented arch technique, specifically designed loops are employed to bring about sufficient force and turning moments to achieve a purely translatory retraction. Most importantly, the moment to force ration (M/F) is determined by the occluso-gingival height, but, as there are intraoral limitations to the spring height, the maximum possible M/F is also limited. Consequently the M/F is no longer constant and activation of the loop to achieve a specific M/F can become critical. This potential problem can be overcome by the use of highly flexible wires, particularly those made of the superelastic alloy nickel titanium. The data presented in this study result from calculations arrived at with the help of a plane numerical model of pseudoelasticity which in turn is based on the finite element method. The calculations are compared with those resulting from experimentations using the orthodontic measurement and simulation system. A variation in the different parameters led to the design of a T-loop with a height and an apical length of 10 mm each. A T-segment made of superelastic NiTi alloy Sentalloy (0.016" x 0.022") was joined to steel horizontal arms. This loop produces a constant M/F ratio of -7 mm and requires no uprighting bends. The range of activation is approximately 15 mm. A superelastic plateau was calculated between an activation of 10.5 mm and 2.5 mm, with a distalizing force from 0.9 N to 0.5 N. The experimental values corresponded to the numerical data. The clinical application of the superelastic T-loop is thus demonstrated. PMID- 8503957 TI - Cuticle surface proteins of wild type and mutant Caenorhabditis elegans. AB - The molecular components of the surface of the free-living nematode Caenorhabditis elegans have been identified by surface-specific radioiodination. Four compartments were defined by fractionation of labeled wild type (N2 strain) adult hermaphrodites. Organic solvents extracted cuticular lipids. Homogenization in detergents released a single, non-collagenous, hydrophobic protein. This is not glycosylated and is a heterodimer of 6.5- and 12-kDa subunits. The third compartment, proteins solubilized by reducing agents, included both the cuticular collagens and the heterodimer. Residual material corresponds to the cuticlin fraction. Larval stages showed a similar pattern, except that the dauer larva had an additional 37-kDa detergent-soluble protein. Other species of rhabditid nematodes displayed similar profiles, and comparison with parasitic species suggests that this simple pattern may be primitive in the Nematoda. A C. elegans strain mutant in cuticular collagen (rol-6) had a pattern identical to that of wild type, but another morphological mutant (dpy-3) [corrected] and several mutants that differ in surface reactivity to antibody and lectins (srf mutants) also had striking differences in surface labeling patterns. PMID- 8503958 TI - High-resolution liquid chromatography of DNA fragments on non-porous poly(styrene divinylbenzene) particles. AB - DNA restriction fragments and PCR products were separated by means of ion-pair reversed-phase high-performance liquid chromatography on alkylated non-porous poly(styrene-divinylbenzene) particles with a mean diameter of 2.1 microns. Optimum resolution was obtained by using an acetonitrile gradient in 100 mM of triethylammonium acetate and a column temperature of 50 degrees C. This allowed the separation of DNA fragments differing in chain length by 1-5% up to a size of 500 base pairs. PCR products could be analyzed directly in less than two minutes with a concentration sensitivity of at least 300 ng/ml. Compared with anion exchange chromatography or gel electrophoresis no desaltation of the purified DNA molecules is required because the volatile buffer system can be readily evaporated. Subsequently, the method was used for the semiquantitative evaluation of the expression of multidrug resistance genes in mononuclear white blood cells. PMID- 8503959 TI - [son Pseudogenes do not contain five repeating elements of the region of complete tandem repeats present in the homologous sequence of the son gene]. AB - Recently we have published a sequence of the coding region of the son gene, containing at least six areas of the tandem repeats [V.V. Bliskovsky, F.B. Berdichevsky, A.V. Tkachenko, M.E. Belova, I.M. Chumakov--Molecularnaya biologiya, 1992, V. 26. P. 793-806; V.V. Bliskovsky, A.V. Kirillov, V.M. Zacharyev, I.M. Chumakov--Molecularnaya biologiya, 1992, V. 26. P. 807-812]. The presence of several areas of tandem repeats with different nucleotide sequences of the repeated elements within one and the same gene supports the proposition that genomic localization of the sequence influences its duplication. Here we present a nucleotide sequence of the son pseudogene isolated as the result of hybridization screening of a human genomic library using the sequence of the son gene as a probe. The comparison of the gene and the pseudogene nucleotide sequences shows that the sequence of pseudogene does not contain five repeated units of an area of the tandem repeats, which are presented in the homology sequence of the son gene. Because the pseudogene was probably generated by the reverse son-gene transcript insertion to the genome, and so the nucleotide sequences of the coding region of the gene and the sequence of the pseudogene were identical at this moment, the differences between the gene and the pseudogene are the results of their evolution after the generation of the pseudogene. Possible factors, influenced the son gene and the son pseudogene evolution are discussed. PMID- 8503960 TI - Three-dimensional structure of the complex between acyl-coenzyme A binding protein and palmitoyl-coenzyme A. AB - Multidimensional 1H, 13C and 15N nuclear magnetic resonance spectroscopy has been used to study the complex between palmitoyl-coenzyme A and acyl-coenzyme A binding protein. The 1H and the 15N spectra of the holo-protein have been almost completely assigned and so has most of the 1H spectrum of the coenzyme A part of the protein-bound ligand. The palmitoyl part of the ligand has been uniformly labelled with 13C and the nuclear magnetic resonance signals of the carbon atoms and their protons have been assigned at the two ends of the hydrocarbon chain. A total of 1251 distance restraints from nuclear Overhauser effects and 131 dihedral angle restraints from three-bond coupling constants provided the basis for the structure calculation. A comparison of 20 structures calculated from these data to the average structure showed that they could be aligned with an atomic root-mean-square deviation of 1.3(+/- 0.2) A for all C, N, O, P and S atoms in protein and ligand. The apo-protein is a four-helix protein and this structure is maintained in the holo-protein. The four alpha-helices are Ac1 of residues 3 to 15, Ac2 from residue 20 to 36, Ac3 from 51 to 62, and Ac4 from 65 to 84. For the four alpha-helices of the peptide backbone of the holo-protein the root-mean-square deviation for the C, C alpha and N atoms was 0.42(+/- 0.08) A. The binding site for the palmitoyl-chain stretches between the N-terminal end of Ac3 where the carboxyl part binds, to the N-terminal of Ac3 where the omega-end of the palmitoyl part binds. The adenosine-3'-phosphate is bound near residues of each of the four helices in an arrangement where it can form salt bridges and/or hydrogen bonds to either backbone or side-chain atoms of Ala9, Tyr28, Lys32, Lys54 and Tyr73. The polar parts of the pantetheine and the pyrophosphate are structured in the bound ligand to form an interface with the solvent. Also the ligand forms a set of non-polar intramolecular interactions where the adenine, the pantetheine, and the palmitoyl-chain are associated, so overall the structure of the bound ligand seems to be organized to protect the lipophilic palmitoyl part from the polar solvent. PMID- 8503961 TI - A paean to Iain Chalmers. PMID- 8503962 TI - Nurses' care during labor: its effect on the cesarean birth rate of healthy, nulliparous women. AB - This retrospective study was designed to determine the influence of nurses' care during labor and delivery on the cesarean birth rate of healthy, nulliparous women. Labor and delivery nurses in a large, nonprofit hospital were grouped according to the cesarean birth rates of their healthy, nulliparous patients in spontaneous labor. Large differences in cesarean birth rates between nurses in the lowest quintile (near 4.9%) and the highest quintile (near 19%) were not explained by differences in maternal age and gravidity, attendance of mother at childbirth class, insurance status, reliance on public assistance, physician who attended labor, use of epidural anesthesia, augmentation of labor, dilation when the nurse assumed care, infant weight, or gestational age. In multivariate analysis, the elapsed time between when the nurse assumed care and birth was significantly shorter for patients of nurses in the lowest quintile of cesarean birth rate (4.4 hrs) compared with patients of nurses in the highest quintile (5.6 hrs). The former were also less likely to have forceps used to assist vaginal delivery than the latter (13% vs 26%). Nurses in the lowest quintile of cesarean birth rates were more likely to use a form to record psychosocial data than nurses in the highest quintile (35% vs 15%). The study suggests that nurses' care during labor is an important factor influencing cesarean birth rates. PMID- 8503963 TI - Satisfaction with childbirth: theories and methods of measurement. AB - Two studies of women's birth experience emphasized the difficulty in evaluating satisfaction with the event. The first study used a quantitative, direct measure of satisfaction in which 91 postpartum women rated their satisfaction with labor and delivery overall and with different aspects of the experience. The second was a qualitative study that examined conceptual issues of women's satisfaction with childbirth using semistructured interviews with nine postpartum women. Content analysis was used to identify themes and categories that contributed to understanding why some women are satisfied and others dissatisfied with the birth experience. Both studies found support for a discrepancy theory of satisfaction. This paper discusses methodologic issues involved in measuring satisfaction with childbirth. PMID- 8503964 TI - Women's satisfaction with birth center care: a randomized, controlled study. AB - This randomized, controlled trial compared women's satisfaction with care at an in-hospital birth center with standard obstetric care in Stockholm. Subjects were 1230 women with an expected date of birth between October 1989 and February 1992, who expressed interest in birth center care, and who were medically low risk. The intervention was the random allocation of maternity care at the birth center or standard obstetric care. Birth center women expressed greater satisfaction with antenatal, intrapartum, and postpartum care, especially psychological aspects of care. Of these women, 63 percent thought that the antenatal care had raised their self-esteem, versus 18 percent of the control group. Eighty-nine percent of the experimental group would prefer birth center care for any future birth, and 46 percent of the control group would prefer standard care. Birth center care successfully meets the needs of women who are interested in natural childbirth and active involvement in their own care, and are concerned about the psychological aspects of birth. PMID- 8503965 TI - Does breastfeeding empower women? Insights from a select group of educated, low income, minority women. AB - A grounded theory study examined the breastfeeding experiences of a small group of educated, low-income, minority women. In-depth interviews were used to collect data. The five themes that emerged as primary descriptors of the experience were against all odds, personal motivation, support, attachment, and telling the world. These themes help to identify the factors that enhanced successful breastfeeding among this select sample of women, and demonstrate that the perception of successful breastfeeding can have an empowering effect on women. PMID- 8503966 TI - The lesbian childbearing couple: a case report. AB - Increasing numbers of lesbians are choosing to bear children. Inadequate information about these women's childbearing concerns, together with discrimination and insensitivity to their needs, places these couples at risk for receiving less than optimal health care. Lesbians who desire children are faced with numerous psychosocial problems that should be addressed by open and sensitive caregivers. Providing care to a lesbian couple demonstrated the ways in which their needs were similar to and different from those of heterosexual couples. PMID- 8503967 TI - Good birthing needs a larger team. PMID- 8503968 TI - Sheila Kitzinger's letter from England: the Baby Friendly Hospital Initiative in times of war. PMID- 8503969 TI - Regarding higher IQs in preterm infants fed human milk. PMID- 8503970 TI - [Monoclonal antibodies. Diagnostic and therapeutic use and prospects for the future]. PMID- 8503971 TI - [Rhesus system polymorphism in the Tunisian population]. AB - A survey carried out on 4129 Tunisian blood donors permitted to evaluate the distribution of Rhesus blood group in Tunisia. The haplotypes frequency were as follow, R1: 0,367 r: 0,284 R0: 0,2082 R2: 0,1218 R': 0,00188 r'': 0,0001. PMID- 8503972 TI - Carcinoma of the gallbladder. PMID- 8503973 TI - Metastatic inefficiency: the scientific basis for resection of liver metastases from colorectal cancer. AB - Hematogenous metastases from primary colon or rectal cancer develop in a definite step-wise fashion. In most patients the primary tumor disseminates to local lymph nodes, to the liver, or to peritoneal surfaces. Lung metastases only develop after considerable progression of the secondary tumor deposits in liver or in lymph nodes. This is considered a metachronous or step-wise progression of the malignant process. Only in a minority of patients is there synchronous spread of the malignancy from the primary site to systemic sites. The dissemination of colorectal malignancy is in great contrast to the dissemination of other malignancies such as breast cancer or melanoma. Considerable autopsy and laboratory data support the metachronous pattern of dissemination. Metastatic inefficiency (overt destruction of a majority of tumor cells within blood vessels or lymphatic channels) explains the preponderance of metastatic deposits in the first capillary bed or first lymphatic network draining a primary colorectal malignancy. These observations constitute the scientific basis for resection of liver metastases from colorectal cancer and the large proportion of patients who can be cured by the surgical resection of one or a few liver metastases. PMID- 8503974 TI - A cytoreductive approach to treatment of multiple liver metastases. AB - Modest benefits and extensive costs have occurred as a result of hepatic artery chemotherapy with fluorodeoxyuridine (FUDR). As a consequence, pump or port infusions of chemotherapy through the hepatic artery are rarely used today. A new cytoreductive approach to the treatment of multiple liver metastases isolated to the liver has been introduced. Induction chemotherapy is used to achieve a response or stabilize disease in the liver. Patients are then selected for surgery, at which time a complete response is achieved through the judicious use of a variety of cytoreductive techniques. In a limited number of patients treated to date the median survival greatly exceeds that reported for intraarterial chemotherapy alone. As experience accumulates, protocols are being modified to decrease the morbidity and maximize the number of complete responders. PMID- 8503975 TI - An approach to histologically diagnosed gallbladder carcinoma following cholecystectomy for presumed benign disease. AB - Five cases of gallbladder adenocarcinoma treated at Surgical Department 2, Maciel Hospital, Montevideo, Uruguay, in a period ranging from 1985 to 1989 and follow up to date are reported. All cases were first diagnosed by microscopic examination of the gallbladder, which had been removed for presumed benign disease; there were no intramucosal carcinomas, and 60% of the cases were classified as Nevin's stage II (submucosal and muscularis). Based on the pattern of spread (mainly direct hepatic infiltration, as well as venous and lymphatic involvement), our radical surgical treatment of gallbladder carcinoma includes cholecystectomy, extended lymphatic clearance (along the porta hepatis or R1, pre and retroduodenopancreatic and hepatic artery R2, and celiac axis R3), and medial hepatectomy (segments, IV, V, and VIII according to Couinaud). Simple cholecystectomy is the treatment of choice in mucosal (T1) neoplasms; otherwise, histologically diagnosed gallbladder carcinoma following cholecystectomy for presumed benign disease calls for reoperation to achieve lymph node dissection and hepatic resection. Overall 2- and 3-year survival was 100% and 80%; mean survival was 50 months. Medial hepatectomy was selected according to gallbladder carcinoma patterns of spread and failures, and entails resection of the parenchyma most frequently involved without compromising liver function, in a quick and safe surgical procedure. PMID- 8503976 TI - Experimental and nonexperimental studies: methodological, ethical, and practical implications in the context of hepatobiliary tumors. PMID- 8503977 TI - Effects of treatments in clinical trials: surgery. AB - The results of surgery for liver cancer (resection or transplantation) have so far been evaluated against older retrospective reports of the survival of series of patients left untreated. Even though it has been taken for granted that "surgical therapy offers the only chance of cure," the validity of this comparison may be challenged. The key problem is that it is impossible from the available evidence to calculate with any reasonable accuracy the expected distribution of survival times of the patients undergoing surgery had they not been treated. Even though there is a group of surgically treated patients who remain alive without signs of recurrence for 5 years or more, the current strategy for surgical treatment may not be favorable for the patient group as a whole. Despite the forseeable difficulties, it seems timely to encourage randomized trials to obtain a proper evaluation of this treatment. PMID- 8503978 TI - Imaging of hepatic focal lesions by nuclear medicine. PMID- 8503979 TI - Computed tomography of liver tumors. AB - Computed tomographic (CT) scan acquisition speed, interscan delay time, and image quality have significantly improved during the past decade. Thus CT has become a standard against which newer techniques such as magnetic resonance imaging (MRI) are validated. Comparison between CT and other modalities, however, lack validity unless the protocol for each procedure is optimized. The authors emphasize the importance of correct CT contrast enhancement techniques in order to obtain reproducible and optimal anatomical information for defining liver tumor morphology, which will determine resectability. Three-dimensional reconstruction using contiguous volume imaging with appropriate enhancement of vessels and tumor also provides important preoperative evaluation for possible resection. Analysis of the hemodynamic status of the liver parenchyma and of the lesions within it is also possible with contrast-enhanced CT although rarely practiced. With appropriate scanning techniques, excellent anatomical and functional information is obtained simultaneously using CT, although histologic specificity often remains insufficient without biopsy. PMID- 8503980 TI - Surgical resection of biliary tract malignancies after interventional radiology treatment. PMID- 8503981 TI - Molecular mechanisms of protease-mediated tumor invasiveness. AB - The biochemical, regulatory, and physiological aspects of plasmin formation by the urokinase-type plasminogen activator (uPA) is discussed and its involvement in cancer malignancy analyzed. Cell surface plasminogen activation has been shown to be essential in extracellular matrix degradation, basement membrane dissolution, and cancer invasiveness and metastasis in a variety of model systems. The ability of cells to produce plasmin on their surface depends on the presence of uPA and plasminogen receptors, and is the basis of the regulation of the plasminogen activating system in vivo. PMID- 8503982 TI - Tumor cell adhesion receptors. PMID- 8503983 TI - Preoperative evaluation of a patient for hepatic surgery. AB - An overview is given of current practice in deciding which patients can undergo a major abdominal operative procedure involving the hepatobiliary system. The criteria developed for individuals with normal and diseased livers are presented, and the unique circumstances of liver transplantation are also addressed. PMID- 8503984 TI - Surgical risk in alcoholic cirrhotic postmenopausal women: prognostic value of levels of hormones. AB - Because increased prolactin levels and hyperprolactinemia in the presence of encephalopathy in males with cirrhosis (alcohol-induced cirrhosis in particular) are associated with statistically increased mortality, we have examined pre surgical levels of prolactin and other hormones, as well as the presence of encephalopathy, in 12 postmenopausal women with end-stage alcohol-induced cirrhosis in relation to liver transplant survival. Levels of estradiol were significantly lower, while luteinizing hormone (LH) and 17-hydroxyprogesterone as well as the ratio of estradiol to testosterone were significantly higher prior to transplantation among the women who survived, compared with non-survivors. A similar pattern was seen for transplant candidates who died before transplantation as compared with still-living candidates. These findings suggest that pre-operative levels of sex steroids and pituitary hormones may have prognostic value in alcoholic cirrhotic postmenopausal women undergoing liver transplantation. PMID- 8503985 TI - Studies in vitro on the influence of ursodeoxycholate sodium salt (UDC) on hepatocyte proliferation. AB - In this study the influence of sodium ursodeoxycholate (UDC) on hepatocyte replicative activity was evaluated using quiescent or primed hepatocytes obtained from normal rats or from rats fed with a protein-free diet, respectively. At physiological concentrations UDC stimulated proliferation in quiescent or primed hepatocytes cultured in minimum essential medium plus insulin, and augmented the replicative activity in hepatocytes already stimulated by low concentration of epidermal growth factor and normal rat serum. However, UDC was not the only bile salt (BS) to show this stimulatory effect on hepatocyte proliferation. The stimulatory activity of BSs was not correlated with their degree of hydrophilia. PMID- 8503986 TI - A study of protein and glycoprotein syntheses in pre-implantation mouse embryos using mini-2D-electrophoresis, video densitometer scanning and computer-image analysis. AB - In the present study, proteins and glycoproteins of mouse embryos at 2-cell, morula and blastocyst stages were analyzed. The techniques of 35S-Met incorporation, ConA antiserum-precipitating ConA-binding proteins, mini-2D electrophoresis, fluorography, video densitometer scanning and the computer-image system were used for analyses. Results of the investigations indicated that proteins and glycoproteins were synthesized by the embryos in a gradual increase manner from 2-cell to blastocyst. A relatively large amount of glycoproteins was synthesized during the morula and blastocyst stages. Two specific small glycoproteins respectively with molecular weights about 6500 and 9000 and PIs at 5.0 and 6.5 were apparently synthesized in the blastocyst but not in the 2-cell or the morula. PMID- 8503987 TI - Cloning and structural-functional studies for 7.5k promoter of Tiantan strain of vaccinia virus. AB - The 7.5k promoter of vaccinia virus Tiantan strain has been cloned by DNA polymerase chain reaction (PCR) method. Results of DNA sequencing analysis showed that in comparison with P7.5k of WR strain, three site mutations and 7 bp of natural deletion existed in the 155 bp fragment of P7.5k of Tiantan strain; four of 7 base pairs deleted were in the late transcriptional initiation region. Although the total mutation rate was high to 6.45%, these two 7.5k promoters of Tiantan strain & WR strain were all early-late promoters and not obviously different in their activities and functional phases. The results above confirmed further that it is a mechanism to keep their genetic stability that some genes of vaccinia virus have multiple transcriptional initiation sites and produce many mRNA with heterologous 5' ends. PMID- 8503988 TI - Structure analysis of streptococcal protein G Fc binding domain. AB - The gene fragment (191 bp) encoding protein G IgG Fc binding domain was isolated by PCR from group G streptococcus (CMCC32138), and a clone containing this gene fragment was found to give fine reactivity to human IgG when expressed in Escherichia coli. The complete nucleotide sequence of the gene fragment was determined. One base pair differs from previously reported protein G nucleotide sequences, and results in an amino acid change (Ala-Thr), but this variation makes no difference in binding to the IgG Fc part by ELISA. The secondary structure of the protein G IgG Fc binding domain has been estimated by circular dichroism and assigned by computer algorithm. It shows a typical alpha-helix region in this domain. By breaking this alpha-helix region with recombinant DNA techniques, a 44 peptide, which contained the N-terminal 27 amino acid residues of this domain, was expressed in E. coli and showed no reactivity to IgG. The hydropathicity of this domain was also analyzed and compared with that of protein A relevant domain. Some similarity was found. These results suggest that the binding mechanism of protein G to the IgG Fc part depends on hydrophobic action which comes from the alpha-helix in protein G molecule, just as protein A binding to IgG Fc part. PMID- 8503989 TI - Binding of HMG proteins to the 5'-flanking sequence of human beta-globin gene. AB - Our previous studies have identified that there are at least three regulatory regions (two negative regions and one positive region) in the 5'-flanking sequence of human beta-globin gene (-610 to +1 bp). The binding of HMG proteins to both negative regulatory regions was examined by the gel mobility shift and DNase I protection assays. In gel mobility shift assay, we observed that HMG proteins 1 and 2 could bind to both negative regulatory regions (NCR1 and NCR2). Using the gel shift competition assay, we identified that the binding proteins between the two regions are different from each other. DNase I protection analysis shows that HMG proteins 1 and 2 only bind to one site (between -560 and 533 bp) in NCR1. However, two protected regions can be detected in NCR2, one between -272 and -252 bp relative to the cap site, the other between -306 and 329 bp. We also observed that HMG proteins 14 and 17 could not bind to both negative regions, so it seems that HMG proteins 1 and 2 may play an important role in the regulation of beta-globin expression through DNA-protein interaction or through protein-protein interaction. PMID- 8503990 TI - T-cell receptors are expressed but down-regulated on intradecidual T lymphocytes. AB - PROBLEM: Dietl et al. considered "intradecidual T cell tolerance towards fetal antigens" with their observation that intradecidual T cells lack immunohistochemically detectable amounts of T cell receptor (TCR) molecules while expressing normal amounts of CD3 molecules during early normal pregnancy (Am J Reprod Immunol. 1990; 24:33-36). METHOD: To reevaluate these findings we examined the TCR and CD3 expression on intradecidual T cells using flow cytometry. CONCLUSIONS: In our study, all intradecidual CD3+ T cells expressed either TCR alpha beta or TCR gamma delta. However, the expression of the CD3/TCR complex on intradecidual T cells was down-regulated. The level of CD3/TCR complex expression on intradecidual T cells was about two-thirds of that on peripheral blood T cells. Further, the proportions of alpha beta+ and gamma delta+ cells in CD3+ cells did not significantly differ between decidua and peripheral blood. PMID- 8503991 TI - Membrane-spanning Fc gamma receptor III isoform expressed on human placental trophoblasts. AB - PROBLEM: Fc receptor for immunoglobulin (Fc gamma R) is an important mediator of immunological functions in the feto-maternal relationship. We have demonstrated by immunohistochemical means that three distinct classes of Fc gamma Rs are expressed in the different cell components of the human placenta. METHOD: In this study, Fc gamma RIII isoform expressed on placental trophoblasts (PTs) was investigated by indirect immunofluorescence and cDNA cloning. PTs, isolated from human term placenta by digestion with proteolytic enzyme, were reacted with monoclonal antibodies (MAb) against the Fc gamma Rs and other surface markers of leukocytes and subjected to flow cytometric analysis. RESULTS: PTs were positively stained with 3G8 and Leu1 1b against Fc gamma RIII, partially stained with MAb against MHC class I, but not with 32.2 (Fc gamma RI), IV3 (Fc gamma RII), or MAbs against CD4, CD19, or CD56, indicating that only low affinity receptor, Fc gamma RIII, is expressed on PTs. The DNA sequence of cloned Fc gamma RIII CDNA from PTs by PCR was identical to that of natural killer (NK) cell isoform, including the position of the stop codon that differs from the granulocyte isoform by several nucleotide substitutions. We further analyzed the susceptibility of PTs against phosphatidylinositol specific phospholipase C (PI PLC) to determine the structural topology of PT isoform. While the reactivity with 3G8 on PTs was not influenced by treatment with PI-PLC, that on granulocytes was significantly diminished with PI-PLC. CONCLUSIONS: This result confirmed that Fc gamma RIII on PTs is a membrane-spanning molecule, and that it is distinctive from PI anchoring Fc gamma RIII on granulocytes. PMID- 8503992 TI - Natural killer cell activity of lymphocytes exposed to ovine, type I, trophoblast interferon. AB - PROBLEM: A member of newly described interferon (IFN) family, ovine trophoblast protein one (oTP-1, now named as ovine type I trophoblast interferon, oTIFN), is a major secretory product of sheep conceptuses during days 11-21 of pregnancy. Type I trophoblast IFN shares high amino acid and nucleotide sequence homology with other mammalian IFN-alpha s and has functional characteristics of IFNs such as antiproliferative, immunosuppressive, and antiviral activities. Moreover, oTIFN is responsible for the antiluteolytic signaling for early pregnancy recognition in sheep. It has been reported that natural killer (NK) cells are recruited to the pregnant uterus and contribute para-immunotrophic effects on growth and differentiation of the conceptus (embryo/fetus and associated membranes). Because IFNs are potent modulators of NK cell activity, the present study examined interactions between oTIFN and sheep and pig NK cells. METHODS: A 51Cr release assay was used to evaluate the effects of various concentrations of oTIFN and IFN-alpha on sheep and pig NK cell activity against K562 and HeLaS3 cells in vitro. Dosages were tested at four effector to target cell ratios. RESULTS: These data provide the first evidence that oTIFN is a potent NK cell activator in vitro. Recombinant human IFN-alpha 1 (rhIFN-alpha) and oTIFN increased (P < 0.01) ovine NK cell cytotoxicity for K562 cells at very low dosages (50 antiviral units (AVU)/ml). Lower doses of oTIFN (15 AVU/ml) were sufficient (P < 0.01) to enable sheep NK cells to kill ovine NK resistant cells, HeLa S3, in a dose-dependent fashion. However, much higher concentrations (> 400 AVU/ml) of oTIFN were needed to increase (P < 0.01) porcine NK cell cytotoxicity. This suggests that oTIFN has some species specificity in activating NK cells. The augmentation of NK cell activity by 100 AVU/ml of oTIFN was effectively neutralized by an anti-oTIFN monoclonal antibody (HL-98) at a dilution of 1:800. CONCLUSIONS: Results of the present study clearly indicate that oTIFN is as active as rhIFN-alpha 1 for activating NK cells in vitro. Immune cells, especially those recruited to the pregnant uterus by conceptus secretory products, may be stimulated/activated by trophoblast IFNs. However, the function of activated NK cells during early pregnancy remains to be determined. PMID- 8503993 TI - Paraimmunology and receptors on decidual T cells: conflict or confirmation? PMID- 8503994 TI - Is an additional vaccination necessary for a successful second pregnancy in unexplained recurrent aborters who were successfully immunized with their husband's lymphocytes before the first pregnancy? AB - PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy? METHODS: The successive pregnancy outcome was analyzed in 22 patients out of 29 unexplained recurrent aborters who had undergone immunotherapy with their husband's lymphocytes according to our previously reported protocol (Takakuwa et al., Am J Reprod Immunol Microbiol. 10:1-9, 1986; Takakuwa et al., Am J Reprod Immunol. 23:37-41, 1990) and had obtained successful outcome between January 1983 and December 1989. In addition, the alteration of blocking antibodies (BAbs), which was evaluated by a one-way mixed lymphocyte culture reaction (MLR) blocking assay between the spouses, was analyzed in 26 patients out of 29. RESULTS: None of the 22 patients underwent further immunotherapy because a significantly high titer of MLR-BAbs had been detected before the new pregnancy. In 19 out of the 21 patients (90.5%), pregnancy was successful. CONCLUSION: Additional immunotherapy is not necessary for patients who have obtained successful results after the initial immunotherapy and are positive for MLR-BAbs after their first delivery. PMID- 8503995 TI - A typical case of reproductive autoimmune failure syndrome in which a patient experienced recurrent abortion, preeclampsia, and intrauterine growth retardation. PMID- 8503996 TI - Effect of ionophore challenge on hamster egg penetration and acrosome reaction of antibody-coated human sperm. AB - PROBLEM: Following the demonstration that antisperm antibodies do not affect the spontaneous acrosome reactions (AR) of human sperm used for the hamster egg penetration assay (HEPA), we evaluated the effect of the ionophore challenge on HEPA and AR of antibody-coated sperm. METHOD: Motile sperm suspensions from donors were exposed to serum and seminal plasma samples with sperm-head-directed antibodies, washed, capacitated, and challenged with ionomycin. RESULTS: The proportion of acrosome-reacted sperm, assessed by fluoresceinated Pisum sativum agglutinin and supravital stain Hoechst 33258, was significantly higher in the antibody-exposed sperm than in the controls (47.0 +/- 13.2% vs. 39.3 +/- 12.1, respectively; P < 0.05). However, the hamster egg penetration rate and index were not significantly different between antibody-exposed sperm and controls (98.0 +/- 3.7% vs. 85.9 +/- 16.2% and 6.64 +/- 4.1 vs. 6.81 +/- 4.8, respectively). Only one of eight test samples with antisperm antibodies, where the highest increase of AR rate compared with controls was observed (55.0% vs. 35.6%) produced a substantial increase of penetrations per oocyte (7.4 vs. 4.1). CONCLUSION: The ionophore challenge enabled us to recognize a subtle effect of anti-sperm antibodies on the dynamics of acrosomal loss, the clinical relevance of which needs to be elucidated. PMID- 8503997 TI - Assessment of circulating agglutinating anti-sperm antibodies in buffalo cows with unexplained infertility and an attempt to identify buffalo sperm isoantigens. AB - The presence of circulating agglutinating anti-sperm antibodies as cause for unexplained infertility of artificially inseminated buffalo cows was assessed. An attempt to identify buffalo sperm isoantigens was also made. The following methods were applied for that purpose: the tray agglutination test (TAT), SDS polyacrylamide gel electrophoresis, and immunoblotting. The results obtained showed that three of 90 sera from buffalo cows with unexplained infertility were positive in TAT (3.3%) and their titers were low. A total of 27 spermatozoal polypeptides reacted positively with the IgG-isoantibodies of one of the sperm agglutinating sera in immunoblotting. Of the control sera 12 also revealed individual variations in the number of positive fractions on the blots. On the basis of comparing the blot with the positive sperm agglutinating serum to the blots of the positive controls, two buffalo sperm isoantigens were identified, with the respective molecular weights of 40 kDa and 120 kDa. In conclusion, circulating agglutinating anti-sperm antibodies are very rarely detected in buffalo cows with unexplained infertility after several artificial inseminations. PMID- 8503998 TI - [Door-to-door vaccination as a strategy for eradication of poliomyelitis]. AB - Due to persistence of poliomyelitis cases in the Pacific Coast of Mexico and particularly in the state of Sinaloa, a house to house vaccination strategy named "Sinaloa Operation" was carried out in 100% of the territory of this state. Sinaloa was divided in small geographical and statistical unit area (AGEB). Simultaneously, teams of nurse carried out a population census of children under five years old and pregnant women. Nurses vaccinated the children with Sabin trivalent vaccine in undiscriminating form. These activities were made in three phases. In the last phase (February 1991) 301, 441 Sabin vaccine doses were administered. This figure represents an extension of the vaccination coverage to the children of the seasonal migrant workers from other parts of the country. As a result of this programme. Sinaloa has not had any other polio case since two years ago. PMID- 8504000 TI - [Echographic dimensions of the kidneys of full-term newborns and their relationship with anthropometric variables]. AB - Ultrasound is the best non-invasive study to evaluate renal morphology in the neonate; so we decided to undergo a study looking for normal renal size in relation with other anthropometric measures. We performed renal ultrasounds in 50 healthy, appropriate for gestational age, term-babies. We found correlation between several anthropometric measures, but the most significant were weight and height. In most cases the left similar to others. It is important to know normal renal dimensions in newborns, since there are diseases that not only are associated with an increased incidence of renal malformations, but also with a reduced renal size such as Down syndrome, or increased renal size such as Beckwith-Wiedemann syndrome. Renal sonogram; term newborn babies; anthropometric correlation. PMID- 8503999 TI - [Granulocytopenia and fever in children with leukemia as indicator of quality of medical care]. AB - OBJECTIVES: 1. To identify the quality degree of medical care in patients with acute leukaemia who had fever and granulocytopenia during the hospitalization period. 2. To establish the relationship between the medical care process and the results in this concern. DESIGN: Retrospective survey. STUDY AREA: Children's Hospital of the Mexican Institute of Social Security. STUDY SUBJECTS: Twenty three patients with acute leukaemia were studied. Also, hospitalization episode of these patients, in which they suffered fever and granulocytopenia, was randomly selected. MAIN MEASUREMENTS: Compliance of diagnostic and therapeutic process was measured during hospitalization, according to the protocolized recommendations made by consensus of the hospital expert group. In order to identify the quality degree of medical care, it was taken into account the protocol compliance besides the results observed in the patients. Results were assessed based on patients' survival to fever and granulocytopenia episode, as well as on fever's duration. The correlation was calculated by using Spearman's coefficient. RESULTS: The medical care quality of the hospital was "adequate" (85% on average). Compliance degree, including the total process was 71%; with diagnostic process 63%, and with therapeutic process 76%. The results observed in the patients were considered as "adequate" (89%). By evaluating individual cases, the medical care quality was considered excellent or adequate in 17 patients (74%) regular in five (22%) and poor in one (4%). Diagnostic process was adequate in 6 patients (26%) regular in 12 (53%) poor in three (13%) and very bad in two (8%). On the other hand, therapeutic process was excellent in 14 patients (60%) regular in one (4%) poor in six (26%) and very bad in two (9%). Results observed in 13 cases were excellent (57%) adequate in eight (35%) regular in one (4%) and very bad in one (4%). The relationship between process and result was 0.41 (P < 0.05) between diagnostic process and result 0.14 and, between therapeutic process and result 0.34. CONCLUSIONS: The medical care quality rendered to patients with leukaemia, who suffered a granulocytopenia episode and fever, was considered as adequate. Therapeutic recommendations were followed accurately, meanwhile, diagnostic process had a lower adherence. A positive relationship between process and result was observed. PMID- 8504001 TI - [Maxillofacial anthropometry tables in healthy newborns]. AB - With the purpose of having parameters which can be useful to evaluate the maxillofacial anthropometric characteristics at birth, we present the results of maxillofacial anthropometric measurements of 22 items in 373 healthy eutrophic newborns of both sexes delivered at the National Institute of Perinatology in Mexico City. Minor alterations of facial structures may indicate the presence of a dysmorphological syndrome such as: wide nasal bridge and wide intercantal distance. This study did not show big increments in the different anthropometric measurements from one week of gestation to the next, except for the bizygomatic and intercommissural measurements. PMID- 8504002 TI - [Child of insulin-dependent diabetic mother: neonatal impact]. AB - Pregnancy and diabetes mellitus have been associated to a high incidence of neonatal morbidity and mortality. The purpose of the present study was to determinate the incidence of macrosomia, congenital malformations and their effect in the neonatal period. We review 42 live infants of insulin dependent diabetic mothers (IDDM) in a third level center. The variables analyzed were: severity of maternal diabetes, sex, weight, gestational age, trophism, Apgar score at one minute, mode of delivery, presence of congenital malformations, morbidity and mortality. The population was divided in three groups: 1. Neonates with appropriate for gestational age (AGA), 2. Large for gestational age (LGA), and 3. Small for gestational age (SGA). According to trophism, 27 (64%) were AGA, eleven (26%) were LGA and four (9%) were SGA. About morbidity, hypoglycemia was more frequent in the LGA. The group of SGA had lower Apgar score at one minute compared with the AGA. There were congenital malformations in seven neonates and being more frequent in the SGA group. The proportion of major malformation was of 4.7%. Fetal hyperinsulinemia is responsible for the morbidity of IDDM, being necessary adequate metabolic control of the mothers before pregnancy and the management of diabetes and pregnancy should be done in a center with experience. PMID- 8504003 TI - [Wounds caused by projectiles of pressure guns in children]. AB - The present study is a survey to analyze the actual situation of the wounds produced by bibi-guns, concerning the damage produced, kind of surgical procedure, clinical evolution, and some general characteristics of the population on study. During a period of two years from May 1990 to May 1992 at the General Hospital of Culiacan, Sin. Six patients from the Pediatric Surgery Department with a diagnosis of wound produced by bibi-guns were studied. All patients required surgical treatment with general anesthesia. The average age of patients was 5.8 +/- 1.5 years, five male and one female; wounds were produced accidentally in four cases and two in a guns-game. The severity of the injury was evaluated, and in two cases their internal injury laid in danger the life of patient. No deaths occurred. PMID- 8504004 TI - [Gordon's syndrome. Report of a case]. AB - A 13 year old girl with hypertension (170/140 mmHg), hyperkalemia (7.3 mmol/L), hyperchloremic metabolic acidosis and normal glomerular filtration rate (creatinine clearance 128 mL/min/1.73 m2), had low plasmatic renin activity (0.20 ng/mL/h), the levels of plasma aldosterone was low (5.5 ng/100mL) and very low transtubular potassium concentration gradient. Other forms of the secondary hypertension were discarded. The patient was treated with salt restriction, oral salbutamol and furosemide, with satisfactory evolution. At present her blood pressure is 130/85 mmHg and potassium, plasmatic levels of 5.3 mmol/L. PMID- 8504005 TI - [Prune belly syndrome associated with cystic adenomatoid malformation of the lung and pulmonary sequestration]. AB - The "prune belly" syndrome classically described in males, has also been described in female patients with a variable incidence. Associations with multiple respiratory tract malformations have been reported which together with urinary tract anomalies and renal failure are often the cause of early mortality. We report the case of a female patient with prune belly in association with cystic adenomatoid malformation of the lung and pulmonary sequestration with a favorable clinical evolution following medical and surgical treatment. PMID- 8504006 TI - [Usefulness of residuals in clinical research]. AB - The simple linear regression analysis, multiple linear regression and logistic regression constitute powerful statistical analysis tools widely used in clinical research. These kinds of analyses are based upon mathematical models which at the same time are established on certain basic assumptions. The regression analysis assumptions are basically: a) that the model is really linear, b) that the distribution of data is normal (from a statistical point of view), c) that the variances of the employed data are homogeneous (homocedastics) and that the included data are independent. The regression diagnostic has become popular as a form to evaluate if the assumptions have been accomplished, one of its most important techniques is the residual analysis. A residual can be defined as the value which measures the distance between the regression line and the corresponding value of the variable "y". Among these kinds of residuals used to evaluate the assumptions of regression are: the crude residual, the standardized, of student and the jackknife. The most useful among them is the jackknife residual. The usefulness and limitations of the residuals in the evaluation of the regression analysis assumptions are described, basically referring to the identification and handling of extreme values (outliers). PMID- 8504007 TI - The effects of hippocampectomy on performance by rats of a running recognition task using long lists of non-spatial items. AB - Unoperated rats, or rats with cortical control lesions or hippocampal aspiration lesions, were trained on a non-spatial delayed non-matching-to-sample task. Once the non-matching rule had been learned, the task was modified so as to assess list memory, with list lengths of up to 32 items. Hippocampectomy induced a significant drop in choice accuracy, that was independent of list length; nonetheless, hippocampectomised rats still performed at better than chance levels. The cortical control lesion appeared to induce an intermediate (though generally non-significant) deficit. It was concluded that hippocampectomy leaves rats still capable of choosing with considerable accuracy on non-spatial working memory tasks that use trial-unique or 'pseudo-trial-unique' stimuli, even under experimental conditions in which a heavy memory load is imposed. PMID- 8504008 TI - Interbulbar reciprocal inhibition in frog olfaction. AB - Frogs were submitted in acute experiments to electrical stimulation of both ipsi- and contralateral homologous olfactory nerve bundles subserving the dorsal olfactory mucosae. Mitral layer responses on one side were recorded. When both stimulations were given at different onset times and equal intensity, the ipsilateral mitral layer response fell to a sharp minimum of 42% when the contralateral stimulation was given 25 ms before the ipsilateral one. When both stimuli were adjusted for maximal temporal inhibition and the intensity of the contralateral stimulation was varied, the amplitude of the ipsilateral response decreased as the intensity of the contralateral stimulation increased until intensity equalization was obtained. This interbulbar inhibition was suppressed either by sagittal transection through the interbulbar adhesion or local infusion of bicuculline in the ipsilateral olfactory bulb. It was unaffected by transection of habenular commissure. These findings suggest first, that the neuroreceptors located in the dorsal olfactory mucosae project to both olfactory bulbs, and second, that it exists at mitral layer level of the frog, a reciprocal inhibition which can subserve frog orientation towards proximal odour source. PMID- 8504009 TI - Role of dermal photoreceptors and lateral eyes in initiation and orientation of locomotion in lamprey. AB - The response to illumination, and the functional roles of skin photoreceptors and lateral eyes, were examined in the adult river lamprey (Lampetra fluviatilis L.). Illumination of one side of the lamprey evoked a turning movement away from the light source followed by locomotion. The lateral eyes were responsible for directing the movements away from the source of light. A selective illumination of one lateral eye consistently evoked a negative phototactic reaction, whereas a selective illumination of tail skin photoreceptors evoked locomotion, without any preferential orientation relative to the source of light. Experiments were performed by video recording the locomotor responses to localized illumination, and analyzed frame by frame. The horizontal turning movement during negative phototaxis consisted of an asymmetric laterally directed mechanical wave, of higher amplitude and lower velocity than the normal locomotory waves, which was propagated from the rostral to the caudal end of the body. PMID- 8504010 TI - Anxiolytic effects of serotonergic interventions in the shock-probe burying test and the elevated plus-maze test. AB - Although serotonergic neural systems have been implicated in the control of anxiety for a number of years, evidence in favour of this role is controversial. The present experiments were designed to further characterize the putative role of serotonin (5-HT) in anxiety, using two pharmacologically validated animal models: the elevated plus-maze and the shock-probe burying tests. If the integrity of 5-HT neural systems is necessary for the expression of 'anxious' behaviors, then disruption of 5-HT systems should produce effects in the plus maze and shock-probe tests that are similar to those of anxiolytic drugs. In the present experiments, serotonergic function was disrupted in rats, either by chemical depletion using the synthesis inhibitor p-CPA, by inhibitory autoreceptor activation using the selective 5-HT1A receptor ligand 8-OH-DPAT, or by electrolytic lesions of the serotonin-containing, dorsal raphe nucleus. p-CPA and dorsal raphe lesions produced robust anxiolytic effects in the elevated plus maze and the shock-probe burying tests, whereas 8-OH-DPAT produced anxiolytic effects only in the shock-probe burying test, and 'anxiogenic' effects in the elevated plus-maze test. Although these results generally support the view that serotonin plays a role in the expression of 'anxious' behavior, the opposite effects of 8-OH-DPAT in the two behavioral paradigms suggest that the 5-HT1A receptor subtype exerts differential control over different types of experimental anxiety. PMID- 8504011 TI - Hemicerebellectomy and motor behaviour in rats. III. Kinematics of recovered spontaneous locomotion after lesions at different developmental stages. AB - The locomotion of rats with a right hemicerebellectomy (HCb) performed in adulthood was compared by means of kinematic analysis with the locomotion of rats with a similar lesion performed on the first postnatal day. The age at which the animals received cerebellar lesion made a significant difference with respect to the locomotor strategies utilized in adulthood. During stance, neonatal operate rats showed a clear hyperextension of both hindlimbs but not of the forelimbs. Their locomotor posture was characterized by spinal flexion with the head held lower than normal. During swing, they showed a tendency towards 'high stepping'. Their steps were regular and symmetrical but hypometric. Adult lesioned animals displayed a marked extensor hypotonia, ipsilateral to the lesion during stance and a relevant hyperflexion affecting both sides, during swing. Alteration of the interlimb coordination and modified sequence of steps were also observed. Thus, a highly asymmetrical, impaired and unstable locomotion was displayed by this group of animals. The present findings demonstrate the importance of the age-at-lesion factor in determining the motor strategies in the recovery of locomotor function after HCb in the rat. This evidence is discussed in the light of the widespread anatomical remodelling already demonstrated following neonatal, but not adult, HCb in rats. PMID- 8504012 TI - Spatial learning during the course of autoimmune disease in MRL mice. AB - The present study examines whether autoimmune MRL-lpr mice develop impairments in learning and memory that correlate with changing severity of lupus-like disease. MRL-lpr mice (n = 20) were tested in the Morris water-maze at 12, 14, 16 and 18 weeks of age. Age-matched controls were congenic MRL +/+ mice (n = 20) that develop the disease much later. Immune status was assessed by the presence of anti-nuclear antibodies (ANA), brain-reactive antibodies, proteinuria, and haematocrit. Learning rates and memory retention did not differ between the substrains, and did not correlate or deteriorate with advancing age and autoimmunity. However, the baseline performance level in autoimmune MRL-lpr mice was shifted, as evidenced by a consistently longer task-solving latencies. Thigmotaxic swimming (along the pool wall) was pronounced in the MRL-lpr group, and was associated with the observed difference in performance. The present study does not support the notion that learning/memory abilities of autoimmune MRL-lpr mice are impaired per se, but may support the hypothesis that the rapid progress of humoral autoimmunity affects the emotionality of lupus-prone mice. PMID- 8504013 TI - Comparison of GM1 ganglioside, AGF2, and D-amphetamine as treatments for spatial reversal and place learning deficits following lesions of the neostriatum. AB - These experiments tested the effectiveness of parenterally administered gangliosides and amphetamine as treatments for spatial learning deficits caused by bilateral lesions of the neostriatum. In Expt. 1, rats were tested postsurgically for 30 days on a shock-avoidance, spatial reversal task. Treatments of gangliosides (GM1 at 30 mg/kg, and AGF2 at 20 mg/kg and 30 mg/kg) and D-amphetamine (2 mg/kg) significantly decreased lesion-induced learning deficits on this task, while treatments of 10 mg/kg AGF2 and the combination of GM1 (30 mg/kg) and D-amphetamine (2 mg/kg) were ineffective. In Expt. 2, rats were given bilateral neostriatal lesions and treated with GM1 (30 mg/kg), AGF2 (20 mg/kg) or D-amphetamine (2 mg/kg) and tested postsurgically for 5 days on a place learning task in the Morris water maze. Only the GM1-treated rats showed a reduction in lesion-induced place learning deficits on this task. Since in both experiments, cell counts near the area of the lesion revealed no differences among any of the brain-damaged groups, it was suggested that the treatments exert their behavioral effects by biochemically activating spared neurons, independent of any ultimate effects they may have on neuronal survival. PMID- 8504014 TI - Comparison of the effects of single and combined neurotoxic lesions of the nucleus basalis magnocellularis and dorsal noradrenergic bundle on learning and memory in the rat. AB - Groups of rats received bilateral destruction of either the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid, the dorsal noradrenergic bundle (DNB) by infusion of 6-hydroxydopamine, or both NBM + DNB (COMB). These lesion groups along with sham operated controls were trained on a food reinforced spatial delayed conditional discrimination task in a T-maze. All four groups were able to attain a criterion of 85% correct responses despite significant group differences in the number of trials to criterion and number of correct responses during training. Performance of the DNB and NBM groups on acquisition trials was significantly lower than controls, significantly higher than the COMB group, but not significantly different from each other. When tested at delays of 30-300 s, all groups demonstrated parallel rates of decline in performance. On reversal learning trials, the NBM and COMB groups were significantly impaired, whereas the performance of the DNB group was better than controls. No significant interaction between the DNB and NBM lesions was observed on any of the behavioral measures. Biochemical analyses demonstrated significant reductions of choline acetyltransferase (ChAT) activity in cortex but not hippocampus of the NBM and COMB groups, and a significant reduction of norepinephrine (NE) in cortex and hippocampus of the DNB and COMB but not the NBM group. The concentration of other monoamine and amino acid neurotransmitters in the lesion groups were unchanged from controls. These results suggest that DNB and NBM lesions produce separate and independent cognitive impairments that do not severely disrupt retention of trial independent (reference memory) and trial dependent (working memory) information on this T-maze task. PMID- 8504015 TI - The effects of fornix and medial prefrontal lesions on delayed non-matching-to sample by rats. AB - The present study compared the effects of fornix lesions and medial prefrontal lesions on a test of object recognition memory, delayed non-matching-to-sample. Neither lesion impaired the acquisition of this non-spatial test of working memory, indeed there was clear evidence that fornix damage resulted in improved non-matching performance during initial acquisition. This improvement in performance could be related to the loss of a spatial bias during the early stages of training. A series of experiments then systematically increased the familiarity of the stimuli (i.e. testing recency rather than recognition judgements). Neither the fornix nor the prefrontal lesions disrupted performance under these conditions, even though this manipulation affected nonmatching in a predictable manner. The same animals were also tested on a spatial forced alternation task in a T-maze (spatial delayed non-matching-to-sample). The animals with fornix lesions performed at chance while the prefrontal animals were mildly, but significantly, impaired. The present findings are considered in the light of a number of seemingly contradictory findings regarding the effects of hippocampal system damage on nonspatial tests of recognition memory. PMID- 8504016 TI - Minimising the risks of PUVA treatment. AB - Psoralen photochemotherapy (PUVA) is a combination of orally administered psoralen and long wave ultraviolet-A radiation (UVA), and is one of the most effective forms of therapy for psoriasis. The unwanted effects of PUVA therapy can be divided into short and long term adverse effects. The short term adverse effects include erythema, pruritus, nausea and headache. While short term adverse effects are limited and reversible after discontinuation of treatment, potential long term adverse effects such as chronic actinic skin damage, dyskeratotic and precancerous skin conditions, nonmelanoma skin cancer, immunological alterations and cataract formation are of greater concern. Long term risks associated with PUVA therapy can be minimised by several measures. Careful patient selection is mandatory; for example, patients with chronic actinic damage and a history of skin cancer may bear a higher risk for the development of new cancers, and previous arsenic intake and ionising radiation also increase the risk of nonmelanoma skin cancers. Certain drug combinations make it possible to lower the UVA dose, which is important because of the dose-dependent increase in the incidence of squamous cell carcinomas in patients treated with PUVA. It has been demonstrated that 200 treatments or a total UVA dose of 1200 J/cm2 seems to be the threshold for development of nonmelanoma skin cancer. Shielding male genitalia during PUVA treatment is essential because of the increased risk of genital squamous cell carcinomas. Yearly dermatological examination to detect skin cancer at an early stage is highly advisable. Sunscreen use, protective clothing and avoidance of sun exposure reduce the uncontrolled dose of solar UV radiation. Other psoralens with a less carcinogenic potential can be used. UVA opaque sunglasses during the entire period of increased photosensitivity after psoralen ingestion help avoid cataract formation. Assignment to PUVA ought to be based on the risk-benefit ratio for the individual patient and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians. PMID- 8504017 TI - Overview of the tolerability profile of clarithromycin in preclinical and clinical trials. AB - Results of studies conducted to characterise local, systemic, reproductive, and mutagenic effects indicate that the new macrolide antimicrobial clarithromycin is well tolerated within reasonable multiples of the intended clinical dose. No adverse effects of clarithyromycin on male or female fertility, perinatal, or postnatal reproduction were indicated by data from rabbits, mice, rats and macaques. No evidence of mutagenic potential was revealed from various in vitro and in vivo study methodologies. Evidence of low potential for ototoxicity, oculotoxicity, hepatotoxicity and nephrotoxicity was provided in studies involving rats, dogs and primates. In agreement with studies with other macrolides, venous irritation potential for the intravenous lactobionate salt formulation was substantial in rabbit studies. In addition, the safety profile of this agent has been evaluated on the basis of adverse reactions and abnormal laboratory values seen in phase I, II and III international clinical trials conducted in adults. The most frequently reported adverse reactions occurring in 3768 patients receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%). Adverse reactions were not serious and were usually rapidly reversible. The incidence of adverse reactions did not vary with gender, race or age. Adverse reaction rates were comparable to or less than those of comparator beta-lactams and macrolides. Overall, clarithromycin appears to be a safe and well-tolerated macrolide antimicrobial agent. PMID- 8504020 TI - Running as fast as we can. PMID- 8504019 TI - The right message. PMID- 8504021 TI - Litigation hazards following failed extractions. PMID- 8504022 TI - The Gibbs Prize in Community Dentistry. PMID- 8504023 TI - Orthodontics--the North American way. AB - The Orthologic award for clinical excellence is granted annually by the Scholarship Committee at the British Orthodontic Conference. It is judged on the presentation of detailed clinical records of three patients treated with an edgewise fixed appliance system. This scholarship is open to practitioners who have gained their initial orthodontic qualification within the last 12 years and provides funds of up to 2000 pounds towards visiting orthodontic centres overseas. With such a generous travel award one could indeed go far! PMID- 8504018 TI - A risk-benefit assessment of tamoxifen therapy. AB - Tamoxifen is the endocrine treatment of choice for all women with hormonally responsive breast cancer. 30 years of experience in both the laboratory and clinical setting have shown tamoxifen to be an effective adjuvant treatment with minor short term adverse effects. However, as therapeutic use has extended to 5 years and beyond, and as clinical trials begin which will assess the effectiveness of tamoxifen as a preventive treatment, concern about possible long term adverse effects is justified. Tamoxifen has an estrogen-like influence on the skeletal and cardiovascular systems, resulting in decreases in both postmenopausal bone loss and low density lipoprotein (LDL) levels. These effects will, it is hoped, result in decreases in the incidences of osteoporosis and coronary heart disease, which are major causes of morbidity and mortality in the postmenopausal age group. Tamoxifen therapy also results in decreased rates of contralateral breast cancer. Long term tamoxifen treatment may result in a small increase in the incidence of endometrial and/or hepatocellular carcinoma, but with millions of women taking tamoxifen for long periods, such small increases in incidence translate to a significant number of women at risk. Tamoxifen is clearly beneficial for short term treatment, but the clinical decision of tamoxifen use in the long term must be made on the individual benefits versus risks of tamoxifen treatment. PMID- 8504024 TI - Profit prophet. AB - Immense resources have been channelled by the business world into the analysis of future trends, control of processes and costs, and the application of the behavioural sciences. Dentistry, still deeply into cottage industry methods and performance, can transform itself through these discoveries by opening up to new ways of seeing its problems and solving them. PMID- 8504025 TI - Apparent deterioration in dental care of 12 year-olds in north London. PMID- 8504026 TI - 'A study of the quality of impressions for anterior crowns'. PMID- 8504027 TI - Temazepam abuse. PMID- 8504028 TI - Magnet retained overdentures using the Astra dental implant system. AB - The Astra Implant System (AIS) is a biologically sound and simple way of providing stability for the complete lower denture where anatomical changes have made retention, stability and comfort difficult to achieve. An ongoing clinical study has been undertaken where 20 patients have been provided with magnet retained overdentures using this implant system. This represented a total of 70 implants placed. Seven implants were removed from four patients (three at exposure, one infection). The remaining implants have been followed up for 12 to 25 months and are considered to have achieved successful osseointegration. All the patients in the study are successfully wearing a lower denture retained by magnets. The overall success rate for the implants placed is 90% but if implants less than 9 mm in length are excluded from the results then the success rate is 97.7%. PMID- 8504029 TI - A longitudinal study of the clinical performance of resin bonded bridges and splints. AB - A total of 382 resin bonded bridges and splints were fitted, in 309 patients, in a teaching hospital. The restorations were evaluated after a period ranging from 5 months to 8 years. During the evaluation period 125 restorations (33%) debonded of which 69 (55%) were rebonded. The survival rates of the rebonded restorations at first, second, third or fourth rebond, where necessary, did not differ from the survival rate of the same restorations up to the first debond. Restorations constructed using the Rochette design had a significantly higher debond rate than the other designs. However, since they also exhibited a high rebond rate Rochette restorations continued to perform well over the study period. Splints had a higher debond rate as did restorations placed in patients in the age group 11 to 20 years, restorations involving more than two abutment teeth, and restorations containing more than one tooth pontic. PMID- 8504030 TI - An assessment of the incidence of punctures in gloves when worn for routine operative procedures. AB - The value of glove wearing as part of dental surgery cross-infection control regimen is negated if gloves are punctured during use. An assessment of the procedures most likely to give rise to glove puncture is therefore of importance. Accordingly, 892 gloves worn by two dentists in general practice were examined for punctures, after being used in one of seven common operative procedures. It was found that gloves used for the treatment procedures investigated had a significantly higher proportion of punctures than unused gloves of the same type. Gloves used for surgical extraction showed the highest proportion punctured (16%). There was no significant difference in puncture frequency between the gloves worn on left or right hands irrespective of procedure. PMID- 8504031 TI - Displacement of a mandibular canine following fracture of the mandible. AB - Much has been written on the aetiology of impacted maxillary canines, but ectopic mandibular canines, being a rarer anomaly, have attracted much less attention. This report describes a case in which the probable aetiology of the displacement of a lower canine was a mandibular fracture through the developing crypt. PMID- 8504032 TI - GDS and CDS--are they on the same side? AB - This paper describes the changing community dental service role in the provision of primary dental care. It sets out those aspects specific to the community dental service (CDS) and identifies areas which are complementary to services provided by practitioners in the general dental service (GDS). It also explores some of the relationships between practitioners working in the GDS and the CDS. PMID- 8504033 TI - Aid given to a dental refugee in World War Two. AB - In 1939, an Austrian/Jewish Dental Surgeon and his wife escaped from Nazi occupied Vienna but had to sacrifice his home, his practice and all his personal possessions and securities. He managed to reach the French consulate in Milan where he was given asylum for a limited period and from there planned his future. PMID- 8504034 TI - Global programme on AIDS. HIV antibody detection in oral fluids. PMID- 8504035 TI - Expanded programme on immunization. Outbreak of diphtheria, update. PMID- 8504036 TI - Barrier function regulates epidermal lipid and DNA synthesis. AB - The stratum corneum, the permeability barrier between the internal milieu and the environment, is composed of fibrous protein-enriched corneocytes and a lipid enriched intercellular matrix. The lipids are a mixture of sphingolipids, cholesterol and free fatty acids, which form intercellular membrane bilayers. Lipid synthesis occurs in the keratinocytes in all nucleated layers of the epidermis, and the newly synthesized lipids are delivered by lamellar bodies to the interstices of the stratum corneum during epidermal differentiation. Disruption of barrier function by topical acetone treatment results in an increase in the synthesis of free fatty acids, sphingolipids and cholesterol in the living layers of the epidermis, leading to barrier repair. Cholesterol and sphingolipid synthesis are regulated by the rate-limiting enzymes HMG CoA reductase and serine palmitoyl transferase (SPT), respectively. Acute barrier disruption leads to an increase in both enzymes, but with a different time curve: increase in HMG CoA reductase activity begins at 1.5 h, whereas the increase in SPT activity occurs 6 h after barrier impairment. Topical application of HMG CoA reductase or SPT inhibitors after acetone treatment delays barrier repair, providing further evidence for a role of cholesterol and sphingolipids in epidermal barrier function. Repeated application of lovastatin to untreated skin results in disturbed barrier function accompanied by increased DNA synthesis and epidermal hyperplasia. Therefore, we have examined the specific relationship between barrier function and epidermal DNA synthesis. After acute and chronic disturbances not only lipid, but also DNA synthesis, is stimulated. Thus, stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis repairs defects in barrier function. The link between barrier function and both lipid and DNA synthesis is supported further by occlusion studies. Artificial barrier repair by latex occlusion prevents an increase in both lipid and DNA synthesis. In addition, increased epidermal lipid and DNA synthesis in essential fatty-acid deficiency can be reversed by topical applications of the n-6 unsaturated fatty acids, linoleic or columbinic acid. These studies may be of relevance in understanding the pathogenesis of hyperproliferative skin diseases, such as ichthyosis, psoriasis, atopic dermatitis, and irritant contact dermatitis. PMID- 8504037 TI - HTLV-1-associated cutaneous disease: a clinicopathological and molecular study of patients from the U.K. AB - The clinicopathological features of eight patients with cutaneous disease associated with HTLV-1 infection are reviewed. All were U.K. residents of West Indian extraction, and two are currently alive. Disease remained confined to the skin in two patients. Five patients with a cutaneous prodromal phase developed leukaemia after a median duration of 124 months (3 months-21 years), and in one of these combination chemotherapy produced a sustained clinical remission for 20 months. Two patients developed cutaneous disease after remission of their leukaemia. Cutaneous lesions were heterogeneous and included localized papules, a generalized papulonodular eruption, diffuse and localized erythematous plaques, pompholyx-like lesions on the palms and soles, and tumours. The histology of the skin lesions was also variable, and consisted of a heavy dermal infiltrate with lymphocytes, histiocytes, plasma cells, eosinophils and cytologically atypical mononuclear cells. Epidermotropism was present in biopsies from five patients. Tumour cells with large, densely staining, pleomorphic nuclei, arranged in rows between collagen bundles, were present in the majority of cases. In one patient the infiltrate also consisted of epithelioid cells and multinucleated giant cells. Six cases were classified histologically as pleomorphic T-cell lymphoma, and two as cerebriform or mycosis fungoides type. Molecular studies revealed a clonal T-cell population associated with monoclonal integration of HTLV-1 provirus in tissue DNA from six patients. In two patients HTLV-1 integration was established retrospectively using enzymatic in vitro amplification of a specific HTLV-1 po1 gene sequence in DNA extracted from paraffin-embedded sections. This study indicates that the clinical and pathological features of HTLV-1-associated cutaneous disease are diverse. Patients may have disease confined to the skin for prolonged periods, either at presentation or following clinical relapse- cutaneous adult T-cell lymphoma. Molecular techniques allow distinction from other types of cutaneous T-cell lymphoma, and provide an opportunity for retrospective studies of archival material. PMID- 8504038 TI - Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions. AB - A strong association exists between guttate psoriasis and group A, beta haemolytic streptococcal infections. To demonstrate the presence of streptococcal specific T cells in psoriatic skin, T-cell lines (TLs) were established from biopsies of lesions from five patients with guttate psoriasis, and compared with TLs from five patients with eczema, five with lichen planus, two with pityriasis rosea and three with nickel contact dermatitis. TLs from purified protein derivative (PPD)-induced delayed hypersensitivity sites in three normal individuals were also studied. All five of the psoriatic TLs responded in a proliferation assay to heat-killed isolates of group A streptococci, compared with only one eczema, two lichen planus and one pityriasis rosea. The response of one nickel contact dermatitis and two PPD TLs to group A streptococci was markedly less than to nickel and PPD, respectively. One of the psoriatic TLs was cloned in the presence of type 5 streptococcal M protein. The nine clones obtained were all CD3+, CD4+, CD45RO+, TCR alpha, beta+, gamma, delta-. However, they were all unreactive with antibodies to TCR V beta 5, 6, 8 or 12. Eight of the nine clones reacted, to a varying extent, to one or two of three preparations of group A streptococci expressing different M proteins. The streptococcal response of four consistently reactive clones from this patient was HLA-DR restricted and inhibited by anti-HLA-DR antibody in a dose-dependent manner. On stimulation these four clones secreted high levels of gamma-interferon and detectable levels of IL-2, IL-10 and granulocyte/macrophage colony stimulating factor (GM-CSF) depending upon the nature of the stimulus, but no IL-4 or TNF alpha production was detected. This study has demonstrated, for the first time, that T lymphocytes specific for group A streptococcal antigens can be consistently isolated from guttate psoriatic lesions. The role of streptococcal specific T cells in the pathogenesis of psoriasis remains to be determined. PMID- 8504039 TI - Increased interleukin 6, but reduced interleukin 1, in delayed pressure urticaria. AB - Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured by bioassays in suction-blister exudates from lesional skin, from skin immediately following a pressure challenge, and from control skin (not subjected to pressure) of patients with delayed pressure urticaria. IL-6 activity in lesional exudates was significantly higher than in exudates from the other two sites. IL-1 activity in lesional exudates was not significantly higher than in the control exudates, but significantly less IL-1 activity was found immediately after pressure challenge than from the control site. PMID- 8504040 TI - The descriptive epidemiology of warts in British schoolchildren. AB - This study set out to determine the prevalence and predictors of warts in British schoolchildren by analysing medical examination data from a national birth cohort study of 9263 British children born 3-9 March 1958. The prevalence of visible warts, according to a medical officer, at the age of 11 was 3.9% (95% confidence intervals 3.5-4.3) and 4.9% (95% confidence intervals 4.5-5.4) at 16. Of the 364 children noted to have warts at the age of 11,337 (93%) no longer had warts at 16. Residence in the south of Britain, having a father with a non-manual occupation, being an only child, and belonging to an ethnic group other than white European were all associated with a decreased risk of visible warts. Region of residence was the strongest predictor of wart prevalence. There were no sex differences in wart prevalence. Warts represent a common source of morbidity in British schoolchildren. Future studies should take into account age, regional factors, social class, family size and ethnic group when comparing wart sufferers with other subjects. PMID- 8504041 TI - The frequency of reactions to sunscreens: results of a longitudinal population based study on the regular use of sunscreens in Australia. AB - Six-hundred-and-three people aged 40 or more years, from Maryborough in central Victoria, were enrolled in a randomized longitudinal study, which required daily application of either a SPF 15+, broad-spectrum, water-resistant sunscreen cream or the cream base without the active ingredients. The study duration was 7 months, from September 1991 until April 1992. One-hundred-and-fourteen (18.9%) of these subjects developed an adverse reaction to the cream they were applying. Patch testing, photopatch testing and scratch testing with the ingredients of the creams revealed that only a small proportion (< 10%) of the inflammatory eruptions were allergic in nature. None of the people tested was allergic to the sunscreen active ingredients. History and examination findings, where available, suggested that the majority of adverse responses were consistent with an irritant reaction, both to the sunscreen preparation and the base cream control. A higher than expected proportion of the people who developed an adverse reaction had a personal history consistent with atopy. Other reactions included acneiform eruptions and contact urticaria. A frequency of reactions to sunscreen preparations of over 15% means that further work is necessary to improve both the formulation of such products, and the manner and conditions under which they are used, to ensure satisfactory compliance. PMID- 8504042 TI - The study of plaques of psoriasis using a scanning laser-Doppler velocimeter. AB - A scanning laser-Doppler velocimeter, able to measure blood flux over a large area without contact with the skin surface, was used for the objective measurement of the vascular changes in psoriasis. Individual plaques were scanned, and tracings of the visible plaque edge taken on to a cellulose-acetate sheet from which area measurements were made using a digitizing tablet. Mean blood flux within plaques was increased fourfold compared with mean background flux. There was a highly significant linear correlation between plaque area measured by tracing and scanning, but area measured by scanning was greater. Detailed study of blood flux outside the visible plaque edge with the scanner, and with a conventional laser-Doppler instrument, showed this was due to a 2-4 mm rim of increased blood flux around plaques. The scanning laser-Doppler velocimeter allows rapid measurement of psoriasis in terms of mean blood flux and area of increased blood flux, and should be useful in the assessment of psoriasis severity and the response to treatment. PMID- 8504043 TI - High frequency, high resolution B-scan ultrasound in the assessment of skin tumours. AB - Sixteen skin tumours and one BCG vaccination granuloma were examined by 20-MHz B scan ultrasound. Images were compared with closely matched histological sections of excised lesions. The correlation between histology and ultrasound was excellent for maximum tumour depth measurements (r = 0.96, P < 0.0001), but less good for maximum width (r = 0.84, P < 0.0001) because of the elastic contraction of tissue at excision. Architectural detail of lesions on histological sections corresponded well with that on ultrasound images. There was a good correlation for heterogeneity (collagen distribution vs. echo pattern (r = 0.86, P < 0.0001)), and between collagen content and echogenicity of lesions (r = 0.69, P < 0.003). Strong correlations were also obtained for echogenicity vs. spacing of collagen bundles (r = -0.65, P < 0.005), echogenicity vs. collagen bundle size (r = 0.58, P < 0.02), and echogenicity vs. cellularity (r = -0.68, P < 0.003). Results for dermatofibroma were atypical, due to paradoxical low internal echogenicity and increased echo absorption. B-scanning is a reliable non-invasive method for assessing tumour dimensions, and has potential for the study of tumour characteristics for diagnostic purposes. PMID- 8504044 TI - A clinicopathological study of scarring alopecia. AB - We have studied 10 cases of scarring alopecia, and investigated the diagnostic reliability of immunofluorescence and histopathology in lichen planopilaris and pseudopelade. In the light of our findings, we discuss the possible pathomechanisms of both disease processes. PMID- 8504045 TI - Chemically induced cosmetic alopecia. AB - Cosmetic causes of scarring alopecia are poorly documented. They include traction alopecia and hot-combing. Recently, another group has presented in the South London area, related to misuse of chemical hair straightening agents. Affected patients are young, female, of Afro-Caribbean origin, and typically display hair loss on the vertex of the scalp. Histology shows a pattern of fibrosis and inflammation characteristic of the physical damage seen with other cosmetic procedures. This histological pattern is distinguishable from other non-cosmetic causes of scarring alopecia. PMID- 8504046 TI - Recurrent erythema multiforme: clinical features and treatment in a large series of patients. AB - Recurrent erythema multiforme is an uncommon disorder. We have reviewed the clinical features and treatment of 65 patients with this condition. The mean number of attacks per year was six (range 2-24), and the mean duration of the disease was 9.5 years (range 2-36) reflecting its chronicity. The majority of patients had oral mucous membrane involvement (69%). In 46 patients (71%) the condition was precipitated by a preceding herpes simplex virus infection. Acyclovir was found to be the most useful first-line treatment, with 55% of patients deriving benefit from either continuous oral acyclovir or a patient initiated 5-day oral course at the onset of herpes simplex virus infection. Of those failing to respond to acyclovir, a small proportion responded to dapsone. The most resistant patients (11) were treated with azathioprine, with complete disease suppression in all cases. PMID- 8504047 TI - Copper vapour laser treatment of port wine stains: clinical evaluation and comparison with conventional argon laser therapy. AB - The copper vapour laser (CVL), emitting at 578 nm, offers potential advantages over the argon laser in the treatment of port wine stains (PWS). In this study, two test areas were performed with each laser using a Hexascan delivery system in 31 patients with PWS. One area was treated at minimal blanching fluence and one at 75% of this fluence. The pulse width was constant for each patient (mean 155 ms). Four-month assessments were made using a fading scale of 0-4, and objectively by an index of light absorbence using reflectance spectrophotometry. The CVL-treated sites had significantly better fading scores than argon laser treated sites at minimal blanching fluence (P < 0.005) and lower absorbence indices (P < 0.05). Fading was significantly greater at minimal blanching fluence than at 75% of this fluence by fading scores and absorbence index values for both lasers. Slight textural and pigmentary changes were seen in a small minority of both CVL and argon tests at minimal blanching fluence only. This study indicates that the CVL is superior to the argon laser in treatment of predominantly red purple or purple PWS. The minimal blanching technique produces greater fading than a lower energy fluence. PMID- 8504048 TI - The effect of short-term low-dose cyclosporin on renal function and blood pressure in patients with psoriasis. AB - The effect of short-term (mean 2.4 months), low-dose (5 mg/kg) cyclosporin A (CyA) on renal function and blood pressure was studied in eight patients with psoriasis. Studies were undertaken before, during and after treatment. Glomerular filtration rate (GFR) post-treatment was significantly higher than pretreatment or during treatment (pre, 119 +/- 7; during, 113 +/- 9; post, 133 +/- 11 ml/min per 1.73 m2; pre vs. during, NS; during vs. post, P < 0.01; pre vs. post, P < 0.05); effective renal plasma flow (ERPF) was unchanged (pre, 515 +/- 38; during, 485 +/- 49; post, 560 +/- 45 ml/min per 1.73 m2). There was no change in the urinary excretion of either albumin or the enzymes N-acetyl-glucosaminidase, lactate dehydrogenase, alanine aminopeptidase and alkaline phosphatase. There was a decrease in exchangeable sodium which persisted post-treatment (pre, 56 +/- 3; during, 49 +/- 3; post, 49 +/- 3 mmol/kg LBM; pre vs. during, P = 0.07; during vs. post, NS; pre vs. post, P = 0.06). Blood pressure assessed as either a single reading, or the mean of a 24 h ambulatory recording, increased during treatment (single reading: pre, 113/73; during, 126/83; post, 114/70 mmHg; mean 24 h: pre, 114/71; during, 123/76; post, 120/72 mmHg). Thus, short-term use of CyA at a dose of 5 mg/kg for the treatment of psoriasis is associated with a significant increase in blood pressure, but only a transient mild reduction in GFR, which did not reach significance. PMID- 8504049 TI - Tetracycline-resistant propionibacteria from acne patients are cross-resistant to doxycycline, but sensitive to minocycline. AB - Antibiotic-resistant propionibacteria are being isolated with increasing frequency from antibiotic-treated acne patients. Minimum inhibitory concentrations (MICs) of three tetracyclines, extensively used in acne therapy, were determined for 46 resistant and 19 sensitive propionibacteria isolates. Sensitive strains were inhibited by < or = 1 microgram/ml of all three tetracyclines. For every resistant strain tested, the MIC of tetracycline exceeded that of doxycycline which, in turn, exceeded that of minocycline. The mean MIC for resistant strains was 20.61 +/- 4.56 micrograms/ml of tetracycline, 9.70 +/- 2.03 micrograms/ml of doxycycline and 1.95 +/- 0.35 micrograms/ml of minocycline. In order to determine whether these strains could be inhibited by concentrations of minocycline achievable in vivo, serum levels of minocycline were determined in acne patients receiving either the recommended dose of 50 mg b.d. (20 males, 14 females), or twice this dose (21 males, 12 females). Serum levels were significantly higher (P < 0.001, Student's t-test) in patients receiving 100 mg b.d. Males on 50 mg b.d. had significantly lower serum levels than females on the same dose (P < 0.05. Student's t-test). For all patients, the mean serum level on high-dose minocycline was 2.46 +/- 0.45 micrograms/ml, compared with 1.38 +/- 0.30 micrograms/ml on the smaller dose. These results indicate that tetracycline-resistant propionibacteria should be considered clinically minocycline sensitive, if patients who harbour such strains are prescribed 100 mg b.d. The recommended dose of minocycline for treating acne, especially in male patients, should be re-assessed. PMID- 8504050 TI - PUVA erythemal sensitivity depends on plasma psoralen concentration and UVA sensitivity. AB - The variation in erythemal sensitivity of the skin during PUVA therapy with oral 8-methoxypsoralen (8-MOP) was examined by measuring both UVA and PUVA erythemal responses, together with plasma 8-MOP concentration, in 27 patients about to start PUVA therapy for psoriasis. The erythema responses were judged visually, and also measured using a reflectance instrument in order to construct dose response curves. No significant association was found between the UVA and PUVA minimal erythema responses. The plasma psoralen concentration showed significant association with the slope of the PUVA erythema dose-response curve. The slopes of the UVA and PUVA erythema dose-response curves were significantly associated, and this association became much stronger when allowance was made for plasma psoralen concentration. These results show that erythemal sensitivity during PUVA therapy is related to both plasma psoralen concentration and inherent UVA sensitivity, but that this relationship is not apparent when sensitivity is judged visually as the minimal erythema response. The association between PUVA and UVA erythemal sensitivity suggests a common pathway in the vascular response induced by UVA radiation, with or without psoralen. PMID- 8504051 TI - Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study. AB - A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25 hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons. PMID- 8504052 TI - Association of hyperimmunoglobulinaemia D syndrome with erythema elevatum diutinum. AB - Hyperimmunoglobulinaemia D and periodic fever syndrome was observed in a female patient with erythema elevatum diutinum. The association of this skin disease with hyperimmunoglobulinaemia D may indicate a pathogenetic relationship. The skin lesions responded to dapsone therapy. PMID- 8504053 TI - Pellagra secondary to 5-fluorouracil. AB - The development of pellagra in a patient treated with 5-fluorouracil for malignant disease is reported. The aetiology of pellagra in this patient is discussed, and the reasons for possible under-diagnosis of pellagra in association with malignant disease considered. We report a patient who presented with the typical skin changes of pellagra. The rash, and an associated acute deterioration in cerebral function, were exacerbated by treatment with 5 fluorouracil. The importance of considering nicotinic-acid deficiency in patients with malignant disease has not been emphasized in the literature. PMID- 8504054 TI - Scleroderma and autoimmune thrombocytopenia associated with ingestion of L tryptophan. AB - We report the occurrence of scleroderma and autoimmune thrombocytopenia in a patient who took L-tryptophan as a muscle-building adjuvant. This is the first time such an association has been reported. PMID- 8504055 TI - Successful treatment of Sweet's syndrome with doxycycline. AB - Two patients with Sweet's syndrome are described, both of whom were treated with doxycycline 200 mg daily, and responded well to therapy. Doxycycline appears to be an effective alternative to corticosteroids for the treatment of Sweet's syndrome. PMID- 8504056 TI - An audit of the clinical diagnosis of sebaceous cyst. PMID- 8504057 TI - Thyroid carcinoma presenting as angio-oedema. PMID- 8504058 TI - Urticarial vasculitis: a presentation of C3 nephritic factor. PMID- 8504059 TI - Merkel cell and squamous cell carcinomas arising in erythema ab igne. PMID- 8504060 TI - Koilonychia in Sherpas. PMID- 8504061 TI - Antibody engineering using Escherichia coli as host. AB - The expression of immunoglobulin fragments with antigen binding activities in E. coli is now routinely possible. Using such expression systems, Fv, Fab, and scFv fragments and single VH domains can be produced as secreted proteins in yields of the order of milligrams per liter. Moreover, expression systems are being rapidly developed for the production of antibody scFv or Fab fragments by repertoire cloning followed by selection. Diverse repertoires of genes encoding VH and VL domains can be isolated by the PCR and cloned for expression using these systems, which allow the selection of recombinants that produce fragments with the desired antigen binding specificities. This technology is rapidly evolving and, coupled with the development of systems for the random mutagenesis and selection of higher-affinity antibody fragments, could, in the longer term, provide an alternative rapid route to hybridoma technology. PMID- 8504062 TI - Mechanisms and therapeutic potential of vanilloids (capsaicin-like molecules). PMID- 8504063 TI - Multidrug resistance in cancers of childhood: clinical relevance and circumvention. PMID- 8504064 TI - Insulin mediators and the mechanism of insulin action. PMID- 8504065 TI - Pharmacology of nerve growth factor in the brain. PMID- 8504066 TI - Molecular mechanisms in acute lung injury. PMID- 8504067 TI - Activation of latent transforming growth factor beta. PMID- 8504068 TI - Antibody-directed enzyme prodrug therapy (ADEPT). PMID- 8504069 TI - Thermodynamic characterization of the structural stability of the coiled-coil region of the bZIP transcription factor GCN4. AB - The thermal stability of a 56 amino acid fragment of GCN4 has been studied by high-sensitivity differential scanning calorimetry and circular dichroism spectroscopy. This fragment contains the leucine zipper and part of the basic region. The thermal unfolding of GCN4-56 is a reversible process and can be well represented by a reaction of the form N2<-->2U, indicating that the unfolding of the leucine zipper is a two-state process in which the helices are only stable when they are in the coiled-coil conformation. As expected, the transition temperature is concentration dependent. At pH 7.06 and a protein concentration of 5 x 10(-4) M the transition temperature is close to 70 degrees C while at 5 x 10( 6) M it is close to 50 degrees C. The enthalpy change for unfolding is 31.5 kcal mol-1 at 70 degrees C. Since the isolated helices are unstable, interactions at the interface between the two helices play a key role in the stabilization of the native dimer. These interactions primarily involve the burial of apolar surface from the solvent (hydrophobic effect) and electrostatic interactions. Structural thermodynamic calculations have permitted a dissection of the magnitude of the various contributions to the total Gibbs free energy of stabilization. PMID- 8504070 TI - Three small ribooligonucleotides with specific arginine sites. AB - Arginine-binding RNA motifs are important to protein-RNA interaction and perhaps also for Archean biochemistry. Selection-amplification was used to isolate three RNAs that are eluted by free arginine from an L-arginine affinity column (Kd approximately 0.2-0.4 mM). The binding sites contain specific internal and bulge loops, whose sequences can include arginine coding triplets. Binding is highly specific for arginine, but all three motifs, like the self-splicing group I intron, also bind guanosine 5'-monophosphate. One site is stereoselective, somewhat preferring D-arginine. PMID- 8504071 TI - Unmasking of hydrogen tunneling in the horse liver alcohol dehydrogenase reaction by site-directed mutagenesis. AB - Primary and secondary kD/kT and kH/kT kinetic isotope effects have been studied as a probe of hydrogen tunneling in the oxidation of benzyl alcohol catalyzed by horse liver alcohol dehydrogenase (LADH). In the case of the wild-type enzyme, isotope effects at 25 degrees C do not clearly support hydrogen tunneling; this result is consistent with a reaction rate that is partially limited by the release of product benzaldehyde. The three-dimensional structure for LADH was used to design site-directed mutations in an effort to enhance the rate of the product release step and to "unmask" tunneling. Substitutions that increased the size of the alcohol binding pocket resulted in minor changes in isotope effects. By contrast, reduction in the size of the alcohol binding pocket through substitution at residues 57 and 93, which are in van der Waals contact with bound alcohol substrate, produced a clear demonstration of protium tunneling from the breakdown of the semiclassical relationship between kD/kT and kH/kT isotope effects. The temperature dependence of kD/kT isotope effects has also been pursued, leading to the conclusion that tunneling does, in fact, occur in the reaction catalyzed by wild-type LADH. Despite the unmasking of protium tunneling in site-directed mutants, substitutions that decrease the size of the alcohol pocket appear to result in less extensive tunneling in the hydride transfer. It is noteworthy that the mutant enzyme (Leu57-->Phe), which shows the greatest evidence of tunneling, has the same catalytic efficiency (Vmax/Km) as the wild type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504072 TI - Sequence-selective alkylation and cross-linking induced by mitomycin C upon activation by DT-diaphorase. AB - Aerobic reduction of MMC by DTD, an obligate two-electron reductase, or chemical reduction by sodium borohydride results predominantly in monoalkylation of DNA at the guanine N7 position within 5'-GG-3' and 5'-GTC-3' sequences. The level of guanine N7 alkylation after DTD reduction increased as the pH was decreased from 7.8 and was optimal at pH 6.6. A similar profile of alkylation was obtained when the major metabolite of DTD-mediated MMC metabolism, 2,7-diaminomitosene, was further reduced by DTD. The sequence preference for DNA interstrand cross-linking (ISC) was also determined using singly end-labeled oligonucleotide duplexes. Reduction of MMC by DTD induced DNA cross-links which were resistant to piperidine cleavage. Exposure of cross-linked DNA to dimethyl sulfate or formic acid and subsequent piperidine cleavage displayed a discontinuity in band pattern which suggested a 5'-CG-3' preference for DNA ISC. Major groove alkylation is proposed to occur via generation, and subsequent metabolism by DTD, of 2,7 diaminomitosene. Cross-linking of DNA, at 5'-CG-3' sequences, is proposed to require the formation of either the protonated leucomitomycin C or the leucoaziridinomitosene during DTD-mediated metabolism of MMC. PMID- 8504073 TI - Laser-induced protein-DNA cross-links via psoralen furanside monoadducts. AB - We have developed a technique for cross-linking DNA binding proteins to DNA using psoralen furanside monoadducts as photoaffinity probes and a continuous-wave argon ion laser (366 nm) as a light source. Several DNA binding proteins (T7 RNA polymerase, UvrB, single-stranded DNA binding protein of Escherichia coli, T4 gp32, and RecA of E. coli) are shown to cross-link to single-stranded psoralen monoadducted DNA oligos differing in length and sequence. Increasing fluences of laser light on a fixed ratio of DNA/protein resulted in an increase in the yield of cross-links. Titration experiments were carried out to measure the apparent cross-linking constant (KappXL) for T7 RNA polymerase or UvrB to a monoadducted 24 mer DNA. The estimated values for the apparent cross-linking constant were in the range of (2-3) x 10(-7) M for both T7 RNA polymerase and UvrB. The efficiency of cross-linking was investigated as a function of the length of adducted DNA and also as a fraction of the total noncovalent binding of proteins of psoralenated DNAs. The results showed that in the cases of T7 RNA polymerase and UvrB cross linking was more efficient with short oligos (8 and 19 mers) as compared to longer oligos (50 mer). A tryptic peptide of T7 RNA polymerase that was conjugated to a psoralen furanside monoadducted 12 mer DNA was isolated by high performance liquid chromatography. Mass spectrometry and amino acid composition of this peptide revealed that it originated from a region between residues 558 and 608 of the primary structure of T7 RNA polymerase. Two other peptides cross linked to oligos were also purified. Repeated attempts to perform Edman sequencing of the peptide-DNA conjugates failed. Overall evidence indicates that photo-cross-linking of furanside monoadducts occurred at multiple sites on the proteins. We have shown that T7 RNA polymerase molecules in a ternary complex arrested at the furanside monoadduct can be cross-linked to the DNA templates with laser light. Evidence suggests that the arrested polymerase molecules existed in multiple conformations on the DNA template. This method of transcriptional cross-linking offers a new method for preparing highly stable elongation complexes for further studies. PMID- 8504074 TI - Functional effects of a G to U base change at position 530 in a highly conserved loop of Escherichia coli 16S RNA. AB - Any base change at position 530 introduced into Escherichia coli on a multicopy plasmid leads to cell death [Powers & Noller (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1042-1046]. It was suggested that these mutants cannot carry out chain elongation. To define more precisely the function of base 530, we have studied ribosomes in which G530 was mutated to U530. In vivo, U530 16S rRNA was incorporated into 30S subunits and could combine with 50S to make 70S ribosomes. 16S rRNA in vitro transcripts containing U530 were assembled into 30S ribosomes, and their activity was tested in defined steps of protein synthesis. Mutant 30S ribosomes were as active as wild-type in poly(U)-dependent poly(Phe) synthesis, P and A-site tRNA binding, and 30S initiation complex formation. 30S initiation complexes, in the presence of 50S, could react with puromycin like the wild-type. The rate, extent, and position of cross-linking of AcVal-tRNA in the P site to 16S RNA were identical in mutant and wild-type ribosomes. Although there appeared to be no defect in 70S initiation complex formation or in direct A-site binding of Phe-tRNA dependent on poly(U), U530 30S ribosomes were nevertheless defective in carrying out synthesis of fMet-Val dipeptide using natural mRNA. Mutant 30S ribosomes were also refractory to streptomycin-induced misreading although no misreading was observed in its absence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504075 TI - Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore. AB - A new macromolecular antitumor antibiotic, C-1027, shows potent cytotoxic effects and DNA cutting activity. The DNA cleaving properties of C-1027 are compared with those of other enediyne compounds such as neocarzinostatin, esperamicin A1, and calicheamicin gamma 1. Even in the absence of thiols or reductants, the antibiotic C-1027 has high DNA breakage ability. Of special interest is the fact that C-1027 causes strand breaks two base pairs apart at specific sites such as 5'-TAT/3'-ATA and 5'-AGA/3'-TCT (cleavage sites in italics) in the two strands. This novel double-stranded cleavage fashion is different from that of calicheamicin gamma 1, which is found to have a 3-bp separation between cleavage sites on the two strands. The asymmetric cleavage pattern to the 3'-side and a competitive experiment with distamycin A reveal minor-groove interaction of double-helical DNA with C-1027. This antibiotic appears to oxidize DNA through hydrogen abstraction predominantly at the C-4' carbon of deoxyribose. The activation mechanism of C-1027, which contains an enediyne chromophore of the esperamicin/calicheamicin type, has been proposed. PMID- 8504076 TI - Dissociation kinetics of actinomycin D from oligonucleotides with hairpin motifs. AB - The dissociation of 7-aminoactinomycin D (7-AM-ACTD) from d(ATGCATATGCAT), d(ATGCAT-T-ATGCAT), or d(ATGCAT-A-ATGCAT) at 20 degrees C cannot be adequately described by a single-exponential decay and requires a fit with two rate constants. The relative contributions of these two rate processes and their temperature dependence can be attributed to the coexistence of two conformational species in solutions. The slow dissociation rate corresponds to oligonucleotides in the dimeric duplex form, whereas the fast rate occurs with those in the hairpin conformation. The increased relative contribution of the faster component at higher temperatures is consistent with the more favorable thermal stability of the hairpin form. Studies with d(ATGCAT-TTT-ATGCAT) and d(ATGCAT-AAA-ATGCAT), which exist predominantly in the hairpin conformation, indicate that 7-AM-ACTD dissociates from these oligomers single-exponentially with rate constants comparable to or less than those obtained for the dimeric duplex of d(ATGCATATGCAT). Equilibrium binding titrations suggest that ACTD binds to hairpins as strongly as to the related dimeric duplexes, suggesting that the stacking geometry of the G.C base pairs at the dG-dC intercalating site of the hairpin stem is not greatly different from that of the dimeric duplex. The considerable variation in the dissociation rates of 7-AM-ACTD from hairpins, however, reflects the varying degrees of DNA minor-groove distortion of the stem duplex resulting from the hairpin loop formation and consequent interactions with the pentapeptide rings of ACTD. The plausibility of our interpretation is further supported by results from electrophoretic measurements, thermal melting profiles, and additional studies with hairpins containing a CGCG or GCGC stem. PMID- 8504077 TI - Aromatic side-chain contribution to far-ultraviolet circular dichroism of helical peptides and its effect on measurement of helix propensities. AB - Peptides of the sequence Ac-XKAAAAKAAAAKAAAAK-amide, where X is Tyr, Trp, or Ala, produce circular dichroism spectra that are typical of the alpha-helix; there are, however, significant differences between the Tyr, Trp, or Ala peptides in the magnitudes of the far-ultraviolet bands. A tyrosine or tryptophan residue is needed in each peptide in order to measure accurately the peptide concentration and the mean residue ellipticity. The N- or C-terminal position is chosen because helix fraying is greatest at each end and the Tyr or Trp residue should influence the helix content of the peptide least at these positions. Amide proton exchange measurements by proton nuclear magnetic resonance spectroscopy indicate that the Tyr, Trp, and Ala peptides possess similar amounts of H-bonded secondary structure. Comparison of the far-ultraviolet circular dichroism and absorption spectra of these peptides suggests that the differences in circular dichroism arise in each case from an induced aromatic circular dichroism band, which is positive for Tyr and negative for Trp. Insertion of one to three Gly residues between the aromatic residue and the rest of the helical sequence reduces the induced aromatic band to insignificant levels. Using this procedure of inserting Gly residues between the Tyr and the rest of the helical sequence, we remeasured the helix propensity of Gly. We find that the Ala:Gly ratio of helix propensities is 40, as opposed to our previous estimate of 100 determined using the Tyr peptide without considering the aromatic contribution of Tyr in the analysis [Chakrabartty, A., Schellman, J. A., & Baldwin, R. L. (1991) Nature 351, 586 588]. PMID- 8504078 TI - Mutagenic analysis of the interior packing of an alpha/beta barrel protein. Effects on the stabilities and rates of interconversion of the native and partially folded forms of the alpha subunit of tryptophan synthase. AB - A series of single and double amino acid replacements in four beta strands of the alpha subunit of tryptophan synthase from Salmonella typhimurium, and alpha/beta barrel protein, was made to study the interior packing of the barrel and to clarify its folding mechanism. The urea-induced unfolding of the alpha subunit is thought to involve a stable intermediate in which the amino folding unit (residues 1-188; helices 0-5, strands 1-6) remains folded while the carboxy folding unit (residues 189-268; helices 6-8, strands 7-8) becomes disordered [Beasty, A. M., & Matthews, C. R. (1985) Biochemistry 24, 3547; Miles, E. W., Yutani, K., & Ogasahara, K. (1982) Biochemistry 21, 2586]. Mutations in strands 1 (A18G and A18V), 6 (Y175Q), 7 (L209V), and 8 (G230A, G230V, and I232V) at the interface between these two folding units show that the effects on the stabilities of the native and intermediate conformations critically depend on the site of the replacement. Although all of these mutations decrease the stability of the native conformation, only the replacements in strand 6, Y175Q, and possibly strand 8, I232V, also perturb the intermediate. Comparisons of the effects of three pairs of double mutants with the effects of the constituent single mutants on stability show that strands 6 and 7 interact in both the intermediate and native conformations, while strands 1 and 8 interact only in the native conformation. Kinetic studies of unfolding indicate that the interactions which occur in the native conformation arise in the preceding transition state. These results demonstrate that the carboxy folding unit adopts an organized structure in the intermediate, contrary to our previous interpretation. The general implication is that the state of folding of one segment of a protein can depend on the presence of another, more stable element of structure. PMID- 8504079 TI - Coralyne binds tightly to both T.A.T- and C.G.C(+)-containing DNA triplexes. AB - Coralyne is a DNA-binding antitumor antibiotic whose structure contains four fused aromatic rings. The interaction of coralyne with the DNA triplexes poly(dT).poly(dA).poly(dT) and poly[d(TC)].poly[d(GA)].poly[d(C+T)] was investigated by using three techniques. First, Tm values were measured by thermal denaturation analysis. Upon binding coralyne, both triplexes showed Tm values that were increased more than those of the corresponding duplexes. A related drug, berberinium, in which one of the aromatic rings is partially saturated, gave much smaller changes in Tm. Second, the fluorescence of coralyne is quenched in the presence of DNA, allowing the measurement of binding parameters by Scatchard analysis. The binding isotherms were biphasic, which was interpreted in terms of strong intercalative binding and much weaker stacking interactions. In the presence of 2 mM Mg2+, the binding constants to poly(dT).poly-(dA).poly(dT) and poly[d(TC)].poly[d(GA)].poly[(C+T)] were 3.5 x 10(6) M-1 and 1.5 x 10(6) M-1, respectively, while the affinity to the parent duplexes was at least 2 orders of magnitude lower. In the absence of 2 mM Mg2+, the binding constants to poly[d(TC)].poly[d(GA)].poly[d(C+T)] and poly-[d(TC)].poly[d(GA)] were 40 x 10(6) M-1 and 15 x 10(6) M-1, respectively. Thus coralyne shows considerable preference for the triplex structure but little sequence specificity, unlike ethidium, which will only bind to poly(dT).poly(dA).poly(dT). Further evidence for intercalation of coralyne was provided by an increase in the relative fluorescence quantum yield at 260 nm upon binding of coralyne to triplexes as well as an absence of quenching of fluorescence in the presence of Fe[(CN)6]4-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504080 TI - Exposure of galactosylceramide to galactose oxidase in liposomes: dependence on lipid environment and ceramide composition. AB - Factors which influence the accessibility, or exposure, of the carbohydrate head group of the glycolipid galactosylceramide (GalCer) at the membrane surface have been examined in lipid model membranes using the technique of galactose oxidase tritiated sodium borohydride labeling. Both the ceramide composition of GalCer and the lipid composition of its membrane environment were varied. We have shown that GalCer is oxidized in a membrane environment, by purification of the labeled galactosyl moiety of the glycolipid by high-performance anion exchange chromatography. Using semisynthetic molecular species of GalCer with acyl chain lengths ranging from 16 to 26 carbons, incorporated into liposome membranes of egg phosphatidylcholine (PC), and reverse-phase HPLC separation of mixtures of the molecular species, we have shown that increasing the fatty acid chain length of GalCer increases its oxidation by galactose oxidase. In addition, the degree of oxidation is reduced when the fatty acid chain of GalCer is hydroxylated. GalCer incorporated into liposomes containing synthetic species of PC with different fatty acid chain lengths (together with cholesterol) was oxidized less as the PC acyl chain length, and hence the bilayer thickness, was increased. The oxidation of GalCer in liposomes composed of sphingomyelin/cholesterol was reduced compared to its oxidation in PC liposomes. Furthermore, changes in the fatty acid chain length of GalCer had no effect on its oxidation in sphingomyelin liposomes. These findings indicate that the ceramide composition and lipid membrane environment can influence the exposure of the lipid carbohydrate, and hence, they could modulate the receptor activity of glycolipids at the membrane surface. PMID- 8504081 TI - Unexpected similarities of the B800-850 light-harvesting complex from Rhodospirillum molischianum to the B870 light-harvesting complexes from other purple photosynthetic bacteria. AB - The B800-850 light-harvesting complex (also called LH2) was isolated from photosynthetic membranes of Rhodospirillum molischianum DSM 119 using molecular sieve and ion-exchange chromatography. Its two bacteriochlorophyll a-binding polypeptides (alpha-subunit and beta-subunit) were purified with a reverse-phase HPLC system. The complete amino acid sequences of both subunits have been determined. The alpha- and beta-subunits consist of 56 and 45 amino acids, respectively, corresponding to molecular weights of 5939 and 5133. In contrast to the B800-850 complexes from other photosynthetic bacteria, the native B800-850 complex from Rs. molischianum is most likely an octamer of monomers with a stoichiometry of three bacteriochlorophyll a and 1.5 lycopenes per alpha,beta subunit. Resonance Raman spectra provide evidence for a 5-coordinated Mg2+ in the BChl, and a carotenoid mainly in the all-trans configuration. A comparison between resonance Raman data from different photosynthetic bacteria indicates that the BChl a-binding site of the B800-850 complex from Rs. molischianum is more similar to the B870 complexes (also called LH1) than to the B800-850 complexes of other photosynthetic bacteria. Sequence similarities especially between the beta-subunits of the B800-850 complex of Rs. molischianum and the B870 and B800-850 complexes of other photosynthetic bacteria agree with this result and provide information on the mode of pigment binding in bacterial antenna complexes. PMID- 8504082 TI - Effect of mutations of ionic amino acids of cytochrome P450 1A2 on catalytic activities toward 7-ethoxycoumarin and methanol. AB - Catalytic efficiencies, percentages of rates of product formation per NADPH oxidized, and rates of product formation per O2 consumed of ionic mutants of cytochrome P450 1A2 (P450 1A2) were studied. Efficiencies of Lys99Glu, Lys453Glu, and Arg455Glu mutants for the hydroxylation reaction toward 7-ethoxycoumarin in the reconstituted system were much lower than that of the wild type (less than 17%), which corresponds to lower turnover numbers for these mutants. In contrast, the catalytic efficiencies for the hydroxylation reaction toward methanol of the three mutants were more than 45% that of the wild type in spite of these mutants' lower turnover numbers. Turnover numbers and catalytic efficiencies of Arg137Leu and Lys401 Glu mutants toward both substrates were comparable to those of the wild type. The electron-transfer rate from the reductase to the heme of P450 1A2 was decreased by 30% upon addition of excess methanol, while it was not influenced by addition of excess 7-ethoxycoumarin. The turnover numbers toward both 7-ethoxycoumarin and methanol as well as the rate constant of electron transfer were decreased by 25-40% by raising the concentration of KCl from 0 to 300 mM in the reconstituted system containing 50 mM potassium phosphate buffer. The turnover numbers toward both substrates of the above-mentioned five ionic mutants caused by tert-butyl hydroperoxide in the absence of the reductase and NADPH were comparable to those of the wild type. The effect of phospholipid constituents on the catalytic activity toward 7-ethoxycoumarin of the wild type was also studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504083 TI - Sizing of bovine heart and kidney pyruvate dehydrogenase complex and dihydrolipoyl transacetylase core by quasielastic light scattering. AB - Quasielastic light scattering (QELS) measurements on several preparations of bovine heart and kidney pyruvate dehydrogenase complex yielded hydrodynamic radii (rH values) ranging from 25.7 to 30 nm. Gel filtration chromatography removed stable aggregates and generated preparations that gave essentially the same rH values of 24.3 +/- 0.6 nm for both complexes. The data were characteristic of a monodisperse system and agree with estimates using cryoelectron microscopy [Wagenknecht et al. (1991) J. Biol. Chem. 266, 24650-24656]. The equivalent hydrodynamic sizes for the heart and kidney complex indicate that the larger number of pyruvate dehydrogenase components in the heart complex (M(r) congruent to 9 x 10(6)) than the kidney complex (M(r) congruent to 7.5 x 10(6)) associate without radial expansion of the heart complex. That accommodation of additional mass is consistent with the space available since even in the more massive complex greater than 80% of the volume within the dimensions of the complex must be occupied by solvent. Preparations of the core of the complex are primarily composed of 60 dihydrolipoyl acetyltransferase (E2) subunits whose inner domains associate to form a pentagonal dodecahedron that is readily observed by electron microscopy (particle radius 10.7-11.3 nm). However, the bulk of E2's mass is present in an exterior multidomain structure. These mobile outer structures are very difficult to observe by standard electron microscopy techniques. Preparations of the core formed stable aggregates that were removed by gel filtration chromatography. QELS measurements gave an rH of 20.1 +/- 0.8 nm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504084 TI - Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) as a 23Na shift reagent for the in vivo rat liver. AB - The use of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (TmDOTP5-) as an in vivo 23Na NMR shift reagent for rat liver was evaluated by collecting interleaved 23Na and 31P spectra. Infusion of 80 mM TmDOTP5- without added Ca2+ produced baseline-resolved peaks from intra- and extracellular sodium without producing any changes in phosphate metabolite resonances or intracellular pH. Several key physiological parameters measured in parallel groups of animals confirmed that liver physiology is largely unaffected by this shift reagent. A direct comparison of TmDOTP5- versus DyTTHA3- showed that after infusion of 5-8 times more DyTTHA3-, the extracellular sodium peak shifted by the same amount as with TmDOTP5-, but the two 23Na resonances were very broad and not resolved. The baseline-resolved peaks with TmDOTP5- allowed us to measure the in vivo T1 and T2 relaxation characteristics of intra- and extracellular Na+. The measured T1, T2s, and T2f values and the relative contributions from the slow and fast T2 components for intracellular Na+ in liver did not differ significantly from the values reported for perfused frog heart. The T1 and T2 relaxation curves of the extracellular Na+ resonances fit a monoexponential function. Analysis of the relative contribution of the fast- and slow-relaxing T2 components from intracellular Na+ resulted in a calculated visibility factor of 69 +/- 4% and the intracellular Na+ concentration calculated from the NMR peak intensity ratio, the measured visibility factor, and literature values of intra- and extracellular volume was 19 mM. These results indicate that TmDOTP5- promises to be quite useful as an in vivo shift reagent for liver and other organs. PMID- 8504085 TI - Proton NMR sequence-specific assignments and secondary structure of a receptor binding domain of mouse gamma-interferon. AB - Previous studies using synthetic peptides and monoclonal antibodies have implicated the N-terminal 39-residue segment as a receptor binding region of mouse gamma-interferon (MuIFN gamma). In this work, we report the solution structure of this fragment (dissolved in water with 40% trifluoroethanol) as determined by proton NMR spectroscopy. The proton sequence-specific assignments were determined from TOCSY and NOESY spectra using established procedures. The secondary structure is characterized by two well-defined alpha-helical regions composed of residues 5-16 and 22-37. These two helices are joined by a loop. No NOESY contacts between the two helical regions were detected. Molecular models consistent with the NMR data were generated for MuIFN gamma (1-39) using distance geometry and restrained molecular dynamics/energy minimization calculations. Comparison with similar N-terminal domains in the published NMR and crystallographic studies on the dimeric human and rabbit IFN gamma suggests some similarities in the structures except that the helical regions in the fragment are longer, and considerable variation may exist in the relative orientation of the two helices in the solution phase. The presence of stronger alpha N sequential NOE's suggests that this peptide is flexible. The absence of NOESY contacts involving the N-terminal tripeptide suggests that this region undergoes rapid segmental motion. The data presented here on MuIFN gamma (1-39), combined with the studies on human and rabbit IFN gamma, suggest that the N-terminal receptor binding domain of the protein can undergo structural changes, the understanding of which may provide insight into the basis for receptor interaction by this lymphokine. PMID- 8504086 TI - Solution structure determination of the heme cavity in the E7 His-->Val cyano-met myoglobin point mutant based on the 1H NMR detected dipolar field of the iron: evidence for contraction of the heme pocket. AB - The 1H NMR spectrum of the cyanomet complex of the sperm whale His[E7]Val myoglobin (Mb) point mutant has been analyzed by 2D methods to yield the assignments for the active site residues, including the substituted Val E7. The dipolar shifted proximal residues are used to quantitatively locate the magnetic axes for the paramagnetic susceptibility tensor in the molecular framework. The orientation of the major axis, which correlates with the ligand tilt, is approximately 15 degrees from the heme normal, as found in wild-type (WT) Mb, but is tilted in a direction rotated approximately 40 degrees toward the heme gamma meso position with respect to WT and similar to that in the His[E7]Gly mutant [Rajarathnam, K., La Mar, G. N., Chiu, M., & Sligar, S. G. (1992) J. Am. Chem. Soc. 114, 9048-9058]. The altered direction of an unchanged tilt angle for the Fe+3-CN unit is shown to be qualitatively consistent with earlier computations of the potential energy surface for MbCO [Kuriyan, J., Wilz, S., Karplus, M., & Petsko, G. A. (1986) J. Mol. Biol. 192, 133-154]. It is concluded that His E7 does not significantly contribute to the ligand tilt but strongly influences the direction of tilt. Deviations between observed and predicted dipolar shifts for the E-helix backbone protons and perturbed patterns of their respective nuclear Overhauser effect between the E-helix and the heme 1,8-methyls are separately analyzed for movement of the E-helix and agree on a translation of the E-helix of the order of 0.8 A in a direction toward the iron. The discrepancy between observed and predicted dipolar shifts for Phe CD1 indicates a approximately 0.5-A movement by the ring parallel to the heme and towards the E-helix. The E-helix and Phe CD1 movements are consistent with a contraction of the pocket to fill the space created by the His-->Val substitution. The correlation between the observed dipolar shifts of the substituted Val E7 side chain and those calculated as a function of rotation of the residue with and without movement of the E-helix confirm the movement of the E-helix and allow a quantitative description of the Val orientation. It is concluded that the dipolar field of the paramagnetic susceptibility tensor provides an important quantitative constraint for defining the heme cavity structure in cyanomet complexes of distal point mutants of myoglobin and hemoglobin. PMID- 8504087 TI - Structure and stability of the molten globule state of guinea-pig alpha lactalbumin: a hydrogen exchange study. AB - A partially folded state of guinea pig alpha-lactalbumin (the A-state or molten globule state), formed by denaturation at low pH, has been studied using hydrogen exchange methods. The overall distribution of exchange kinetics, measured by 1-D NMR, suggests that fewer than 20 amides in the structure are involved in highly persistent residual structure, although CD results suggest that many other parts of the chain are folded, for a significant proportion of the time, into less stable structural elements. The pH-jump experiments show that some amides that are strongly protected from exchange in the native state become freely accessible in the A-state but that conversely a majority, at least, of those that are slow to exchange in the A-state retain that protection in the native state. This suggests that the persistent structure in the A-state is native-like although the possibility that nonnative like structural elements persist cannot be eliminated. Resonance assignments for key residues in the NMR spectrum of the native state have enabled us to use the pH-jump method also to identify the majority of the most protected amides in the A-state: they are located in two hydrophobic segments, corresponding to the B- and C-helices of the native structure. This strongly suggests that the most persistent structure of the A-state includes these regions. A variety of lines of evidence, including fluorescence quenching data and, most remarkably, very effective protection from exchange of an indole NH in a tryptophan side chain, suggest that some form of hydrophobic core in the helical domain of the native structure persists in the A-state, although without the stereochemical rigidity of the native tertiary structure. The other domain of the native structure, including the beta-sheet, appears not to contain structural elements which persist to the same extent in the A-state, emphasizing that the molten globule is highly heterogeneous, in terms of the stability and specificity of both backbone and side chain interactions. PMID- 8504088 TI - Cloning and functional expression of dendrotoxin K from black mamba, a K+ channel blocker. AB - Mamba dendrotoxins, 7K M(r) polypeptides with three disulfide bonds, selectively inhibit certain fast-activating, voltage-sensitive neuronal K+ channels and have been instrumental in their identification, localization, and purification. However, derivatives with more refined specificity are essential to define the structural and functional properties of the multiple subtypes known to reside in the nervous system. Hence, utilizing a constructed cDNA library from the venom glands of the black mamba (Dendroaspis polylepis), the gene encoding dendrotoxin K was isolated, amplified, and expressed as a maltose-binding fusion protein in the periplasmic space of Escherichia coli. After cleavage of the chaperone from the affinity-purified product, a recombinant protein was isolated and shown to be identical to native dendrotoxin K in its N-terminal sequence, chromatographic behavior, convulsive-inducing activity, and binding to voltage-activated K+ channels in bovine synaptic membranes. This successful expression of refolded active toxin, in adequate yield, makes possible for the first time the preparation of mutants with specificity tailored for each K+ channel subtype, based both on the recently derived three-dimensional structure of alpha dendrotoxin and the identified binding site on cloned K+ channels. PMID- 8504089 TI - Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins. AB - Superoxide production by phagocytic white blood cells requires the assembly of an NADPH oxidase from membrane and cytosolic proteins. Recombinant cytosolic proteins p47phox and p67phox and neutrophil membranes were used to purify a third cytosolic component that is necessary and sufficient for cell-free reconstitution of NADPH oxidase. The component was isolated as a complex of rho-GDP dissociation inhibitor (rho-GDI) and two members of the rho subfamily of ras-related guanine nucleotide binding proteins, rac2 and CDC42Hs. Oxidase reconstitution with these pure cytosolic proteins was unaffected by GTP gamma S but was inhibited by GDP beta S, suggesting that the active complex contained endogenous bound GTP. Direct binding of rho-GDI to the GTP gamma S-bound forms of these G-proteins was demonstrated by gel filtration following exchange with radiolabeled guanine nucleotide. rho-GDI was shown to be nonessential for cell-free oxidase reconstitution in experiments that compared the activities of pure recombinant forms of these G-proteins. Recombinant rac augmented superoxide production, while recombinant CDC42Hs, which shares 70% amino acid sequence identity with rac, did not. Three highly conserved regions of rac1 and rac2 were noted as markedly divergent in CDC42Hs. It is proposed that one or more of these regions of rac may be involved in the specific interaction of rac with the other NADPH oxidase protein(s). PMID- 8504090 TI - Sequential phosphorylation of rhodopsin at multiple sites. AB - Photolyzed rhodopsin is phosphorylated at multiple serine and threonine residues during the quenching of phototransduction. Sites of phosphorylation by rhodopsin kinase have been localized to the C-terminal region of rhodopsin, but no information was available on the kinetics and identity of phosphorylated residues. To determine the kinetics of phosphorylation at specific residues, the phosphorylated C-terminal peptide of rhodopsin (330DDEASTTVSKTETSQVAPA) obtained by proteolysis of rhodopsin with endoproteinase Asp-N was subjected to further subdigestion followed by electrospray mass spectrometry. Analysis of monophosphorylated peptide revealed that the major initial phosphorylation site is 338Ser. The analysis of di- and triphosphorylated peptides indicated that 343Ser or 336Thr residues are subsequent phosphorylation sites. These three residues, located in the C-terminal region of rhodopsin, are likely to be key phosphorylation sites of rhodopsin during the quenching of phototransduction. Identification of the kinetics of phosphorylation will facilitate understanding the functional significance of rhodopsin phosphorylation at multiple sites and the mechanism of rhodopsin kinase action. PMID- 8504091 TI - Photoaffinity labeling of skeletal myosin with 2-azidoadenosine triphosphate. AB - The purine binding site of ATP on skeletal muscle myosin has been photoaffinity labeled with 2-azidoadenosine diphosphate (2-N3ADP). 2-N3ADP was stably trapped at the active site (t1/2 approximately 5 days, 0 degree C) by complexation of the two heavy chain reactive thiols (Cys-697 and Cys-707) with Co(III)phenanthroline. Photoincorporation occurred only in the 23-kDa NH2-terminal tryptic fragment of the heavy chain. Extensive serial digestion of photolabeled subfragment 1 of myosin by trypsin and subtilisin yielded a series of labeled peptides which were purified by HPLC. Sequence and radiolabeling analysis of eight photolabeled peptides all indicated that tryptophan-130 was the only labeled residue. This site of labeling confirms earlier photolabeling studies with the non-nucleotide ADP analogue, 2[(4-azido-2-nitrophenyl)-amino]ethyl diphosphate (NANDP), which also labeled Trp-130 [Okamoto, Y., & Yount, R. G. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1575-1579]. Comparison of the structures of 2-N3ADP and NANDP indicate that their azido groups can be superimposed if both analogues bind to the active site in an extended conformation in a manner analogous to the anti conformation of ATP. PMID- 8504092 TI - An amino-terminal fibronectin fragment stimulates the differentiation of ST-13 preadipocytes. AB - Differentiation of ST-13 preadipocytes into adipocytes was inhibited almost completely by addition of rat plasma fibronectin (FN) (approximately 100 micrograms/mL), but was reversed by GRGDSP cell recognition peptide (1.5 mM) and anti-alpha 5 beta 1. On the contrary, the thermolysin digest of FN stimulated adipocyte differentiation in a dose-dependent manner, in which remarkable increases in the values of the differentiation indexes, the number of adipocytes (8-fold above the control), glycerophosphate dehydrogenase (GPD) activity (12 fold), and triacylglycerol content (5-fold), were observed by inclusion of the thermolysin digest (100 micrograms/mL). The increase in GPD activity by the thermolysin digest was inhibited remarkably (about 70% inhibition) by an antibody directed to the amino-terminal fibrin-binding (Fib 1) domain of FN and slightly (about 15%) by an antibody directed to the central cell-binding (Cell) domain, but not by anti-gelatin-binding domain and anti-carboxy-terminal fibrin-binding domain. Treatment of ST-13 cells by a purified 24K fragment (100 micrograms/mL) derived from the Fib 1 domain caused an over 20-fold augmentation of the GPD activity, accounting for a major part of the differentiation stimulatory activity of the thermolysin digest. The differentiation stimulatory effect of the 24K Fib 1 fragment was not affected by either GRGDSP peptide or anti-alpha 5 beta 1. Thus, FN can regulate adipose development of ST-13 cells by its two antipodal, inhibitory and stimulatory, activities, the latter of which is expressed only upon fragmentation. Proteolytic cleavage of FN may play an important role in controlling the action of FN on adipocyte differentiation. PMID- 8504093 TI - Regulation of rat hepatic lipase by the composition of monomolecular films of lipid. AB - The regulation of hepatic lipase (HL) by the lipid composition of monomolecular substrate films was examined using a monolayer technique at constant surface pressure. HL-catalyzed hydrolysis of triacylglycerol, a poor substrate for HL in pure monomolecular films, was activated by diradylglycerol and its phosphorylated derivatives in mixed films containing 10 mol % triacylglycerol. When triacylglycerol was progressively diluted with dialkylglycerol, triacylglycerol hydrolysis by HL was maximal between 90 and 98 mol % dialkylglycerol. The best activators, dialkylphosphatidic acid and dialkylphosphatidylethanolamine, increased triacylglycerol hydrolysis 13-14-fold, and the enhancement of HL catalyzed triacylglycerol hydrolysis by the activator lipids was inversely related to the average mean molecular area of the mixed films. The hydrolysis of 5 mol % triacylglycerol in mixed films that also contained phosphatidylcholine and 0-20 mol % cholesterol was inhibited approximately 80% when the concentration of cholesterol was 10-13 mol %. Interestingly, between 15 and 17 mol % cholesterol the hydrolysis rate was restored to about 50% of the uninhibited rate, but at 20 mol % cholesterol this value decreased back to 80% inhibition of hydrolysis. The hydrolysis of phosphatidylethanolamine in mixed films with 0-20 mol % cholesterol decreased approximately 30% in films containing 10-12 mol % cholesterol. However, at 15 mol % cholesterol the hydrolysis rate was restored to the same level observed for a pure phosphatidylethanolamine film. This enhancement of HL activity occurred at about the same cholesterol concentration as the restoration of triacylglycerol hydrolysis observed for the triacylglycerol/phosphatidylcholine/cholesterol films.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504094 TI - Apolipoprotein A-I-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of pre-beta high-density lipoprotein particles. AB - Apolipoprotein A-I-(apoA-I-) containing lipoproteins isolated by immunoaffinity chromatography can be divided into two general subfractions on the basis of the presence [Lp(AI + AII)] or absence [Lp(AI - AII)] of apoA-II. The Lp(AI - AII) subfraction can be further subfractionated into two subgroups with pre-beta mobility as well as those of alpha mobility. We have characterized the Lp(AI - AII) and Lp(AI + AII) subfractions after the removal of pre-beta high-density lipoproteins (pre-beta-HDL) to compare only the two subfractions with alpha mobility. The Lp(AI - AII) and Lp(AI + AII) of alpha mobility, while both heterogeneous subfractions, share many gross features in common. Both subfractions were predominantly spherical in shape, had similar conformation of apoA-I as investigated by circular dichroism and specific endoproteases, and had similar contents of phospholipids, phospholipid species, triglycerides, and cholesterol ester. However, there was significantly less protein (-10%) and more free cholesterol (+46%) in the Lp(AI - AII) subfraction than in the Lp(AI + AII) subfraction. We investigated the generation of pre-beta-HDL from both the Lp(AI - AII) and Lp(AI + AII) subfractions during incubation with low-density lipoproteins and cholesteryl ester transfer protein. We found that both Lp(AI - AII) and Lp(AI + AII) subfractions were capable of generating pre-beta-HDL-like particles. Our results suggest that the formation of pre-beta-HDL involves dissociation of apoA-I from both Lp(AI - AII) and Lp(AI + AII) subfractions. These results refine a model describing the cycling of apoA-I between pre-beta HDL and alpha-HDL linked to the movement of cholesteryl esters through HDL. PMID- 8504095 TI - Insulin receptor autophosphorylation. I. Autophosphorylation kinetics of the native receptor and its cytoplasmic kinase domain. AB - Kinetic analysis of autophosphorylation was done using a non-Michaelis-Menten kinetic model. This model describes autophosphorylation in terms of a fast reaction phase, a slow reaction phase, and a partition function for the two phases. Kinetic parameters determined by this new approach show that insulin stimulates autophosphorylation by promoting (1) a 10-fold increase in the rate constant for the fast phase of the reaction and (2) a 2-fold increase in the partition function favoring the fast phase. Insulin did not significantly affect the binding constant for ATP in this fast phase. Kinetic parameters obtained for the cytoplasmic kinase domain were similar to those obtained for the native insulin receptor in the absence of insulin. The insulin receptor has three subdomains encompassing its seven autophosphorylation sites. The juxtamembrane sites react primarily in the slow kinetic phase, favored by the absence of stimulation and low ATP concentrations. The carboxy-terminal and central autophosphorylation subdomains react primarily in the fast kinetic phase, favored by raising the ATP concentration and/or the presence of insulin. These observations demonstrate that: (1) both ATP and insulin regulate reaction in each autophosphorylation subdomain, (2) insulin stimulation occurs predominantly in the central and carboxy-terminal regions, and (3) autophosphorylation observed with the cytoplasmic kinase domain was similar to native insulin receptor in the absence of insulin. These findings are consistent with conclusions based on the kinetic analysis of autophosphorylation. PMID- 8504096 TI - Insulin receptor autophosphorylation. II. Determination of autophosphorylation sites by chemical sequence analysis and identification of the juxtamembrane sites. AB - Autophosphorylation sites of the human insulin receptor were identified by microsequence analysis of 19 discrete tryptic [32P]phosphopeptides, purified from the autophosphorylated cytoplasmic kinase domain (CKD). Seventeen phosphopeptides were generated by cleavage at Arg and/or Lys, but two phosphopeptides were generated reproducibly by anomalous cleavages. Two new sites were identified in the juxtamembrane region of the intact insulin receptor beta-subunit (the amino terminus of the CKD), including phosphotyrosines 965 and 972. Three sites in the central region, including phosphotyrosines 1158, 1162, and 1163, were identified from six phosphopeptides; tyrosine at 1158 was the least phosphorylated. Monophosphopeptides contained phosphotyrosine at either residue 1158 or 1163, but not at 1162. Bisphosphorylation included phosphotyrosines only at 1162 and 1163. The two autophosphorylation sites near the carboxy terminus were found in seven phosphopeptides, including phosphotyrosines at 1328 and 1334. When mapped by reverse-phase high-performance liquid chromatography, these phosphopeptides eluted in the order central domain, first; carboxy-terminal region, second; and juxtamembrane (amino-terminal) domain, last. PMID- 8504097 TI - Voltage dependence of facilitated arginine flux mediated by the system y+ basic amino acid transporter. AB - Two-microelectrode voltage clamp was used to measure membrane currents resulting from flux of cationic amino acids in Xenopus oocytes expressing the cloned dual function ecotropic murine leukemia virus receptor/system y+ transporter. At membrane potentials ranging from +20 mV to -120 mV, arginine influx obeyed Michaelis-Menten kinetics. At concentrations from 0.01 to 1 mM, influx increased exponentially with membrane hyperpolarization (e-fold increase/-59 mV). Efflux from oocytes preloaded with arginine increased exponentially with depolarization (e-fold increase/+52 mV). Kinetic analysis based on an iso uni uni facilitated transport model suggests that the effect of voltage on steady-state flux arises largely from charge movement across the membrane field during the conformational transition of the unliganded transporter which switches the substrate binding site from one membrane face to the other. This charge movement would facilitate rapid increases in intracellular arginine concentrations in response to hyperpolarization, a property which could play a role in modulating nitric oxide synthesis in some types of cells. PMID- 8504098 TI - Influence of amino acid replacement at position 198 on catalytic properties of zinc-bound water in human carbonic anhydrase III. AB - Carbonic anhydrase III, found predominantly in skeletal muscle, is the least efficient of the mammalian carbonic anhydrases in catalyzing the hydration of CO2. Phenylalanine-198 is located on the hydrophobic side of the active-site cavity with its phenyl ring in the proximity of the catalytically active zinc bound water. We replaced phenylalanine-198 in human carbonic anhydrase III with seven other amino acids (Ala, Asn, Asp, His, Leu, Tyr, Val) using site-directed mutagenesis. The catalytic properties of these enzymes were determined by stopped flow spectrophotometry, and the exchange of 18O between CO2 and water was measured by mass spectrometry. All of the mutants had maximal values of kcat/Km for the hydration of CO2 enhanced, and five of the mutants had the pKa of the zinc-bound water increased compared with the wild-type enzyme. The largest effects were observed with the replacement Phe-198-->Asp which increased the maximal kcat/Km 140-fold and increased the pKa of the zinc-bound water from near 5 to 9.2. A Bronsted correlation was observed between log(kcat/Km) for hydration of CO2 and the pKa of the zinc-bound water (correlation coefficient r = 0.92); in addition, this pKa was inversely correlated with hydrophobicity of the residue at 198 (correlation coefficient r = -0.83). A direct correlation between the logarithm of the maximal kcat/Km for hydration and the logarithm of the pH independent value of Ki for inhibition by cyanate (r = 0.95) indicated that the effect of the mutations at residue 198 occurred in large part by enhancement of the rate of dissociation of the enzyme-bicarbonate complex. PMID- 8504099 TI - Catalytic mechanism of yeast adenosine 5'-monophosphate deaminase. Zinc content, substrate specificity, pH studies, and solvent isotope effects. AB - Adenosine 5'-monophosphate (AMP) deaminase from baker's yeast is an allosteric enzyme containing a single AMP binding site and two ATP regulatory sites per polypeptide [Merkler, D. J., & Schramm, V. L. (1990) J. Biol Chem. 265, 4420 4426]. The enzyme contains 0.98 +/- 0.17 zinc atom per subunit. The X-ray crystal structure for mouse adenosine deaminase shows zinc in contact with the attacking water nucleophile using purine riboside as a transition-state inhibitor [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284]. Alignment of the amino acid sequence for yeast AMP deaminase with that for mouse adenosine deaminase demonstrates conservation of the amino acids known from the X-ray crystal structure to bind to the zinc and to a transition-state analogue. On the basis of these similarities, yeast AMP deaminase is also proposed to use a Zn(2+) activated water molecule to attack C6 of AMP with the displacement of NH3. The pKm and pKi profiles for AMP and a competitive inhibitor overlap in a bell-shaped curve with pKa values of 7.0 and 7.4. This pattern is characteristic of a rapid equilibrium between AMP and the enzyme, thus confirming the rapid equilibrium random kinetic patterns [Merkler, D. J., Wali, A. S., Taylor, J., Schramm, V. L. (1989) J. Biol. Chem. 264, 21422-21430]. The Vmax of the reaction requires one unprotonated and one protonated group with pKa values of 6.4 +/- 0.2 and 7.7 +/- 0.3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504100 TI - Determination of Fe-CO geometry in the subunits of carbonmonoxy hemoglobin M Boston using femtosecond infrared spectroscopy. AB - We have undertaken ultrafast infrared (IR) spectroscopic studies in order to elucidate the geometry of bound CO in the alpha and beta subunits of hemoglobin (Hb) M Boston 13CO. Hb M Boston is a mutant human Hb in which the distal histidine in the alpha subunits is replaced by a tyrosine. The IR absorptions of bound 13CO fall at 1925 cm-1 for the alpha subunits and 1907 cm-1 for the beta subunits. Despite a difference of nearly 20 cm-1 in these peaks, the measured anisotropies of the bound 13CO depletions following 30% photolysis are nearly identical, with values of -0.142 +/- 0.002 obtained for the alpha subunits and 0.140 +/- 0.003 obtained for the beta subunits. These translate to values of 20 degrees +/- 1 degree and 21 degrees +/- 1 degree for the values of the average angles between the CO bond and the normal to the heme planes in the alpha and beta subunits, respectively. Our present results and the work of previous investigators [Nagai, M., Yoneyama, Y., & Kitagawa, T. (1991) Biochemistry 30, 6495-6503] suggest that a change in the polar interactions of the bound CO with the heme pocket environment upon substitution of tyrosine for the distal histidine and a less bent structure for the Fe-C-O unit in the alpha subunits are responsible for the difference in the bound CO absorption frequencies in the alpha and beta subunits. A spectrum of the depletion of the bound 13CO peaks following photolysis indicates that both subunits photodissociate CO with the same quantum yield and neither subunit exhibits significant recombination within 1 ns. PMID- 8504101 TI - Time-resolved resonance Raman study on the binding of carbon monoxide to recombinant human myoglobin and its distal histidine mutants. AB - Time-resolved resonance Raman (RR) spectra of the recombined species of photodissociated CO with recombinant human myoglobin (Mb) and several E7 mutants, in which distal His was replaced by Gly (H64G), Gln (H64Q), Ala (H64A), Ile (H64I), Val (H64V), and Leu (H64L) through site-directed mutagenesis, were observed in the time range -20 ns to 1 ms following photolysis. The Fe-CO stretching (VFe-CO) RR band was observed successfully with pulse excitation when the laser power was greatly reduced. H64H, H64G, and H64Q gave the VFe-CO band at 505-510 cm-1 in their stationary states. In their recovery processes 1-100 microseconds after photodissociation, a broad transient band was observed at slightly lower frequencies than those of their equilibrium structures for H64G and H64Q, but a transient VFe-CO band corresponding to the so-called "open" form was not identified around 490 cm-1 for any of the three species. A second group, H64A, H64I, H64V, and H64L, gave the main VFe-CO band at 490-495 cm-1 with a shoulder around 510 cm-1 (except for H64L) in the stationary state and exhibited a much faster recovery than the first group. These latter four species gave a broad transient band around 492-500 cm-1 in the time range of 100-1000 ns, while the approximately 510 cm-1 shoulder appeared much later. The equilibrium relative intensity of the two bands was attained at 500 microseconds, suggesting that the interconversion between the two forms is slower than 100 microseconds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504102 TI - Binding of horseradish, lignin, and manganese peroxidases to their respective substrates. AB - The present study utilizes 1H NMR spectroscopy to characterize the binding of substrate to heme active site of three different peroxidases, horseradish peroxidase, lignin peroxidase, and manganese peroxidase. Information has been obtained on the site of p-cresol binding to the active-site cavity of the cyanide derivative of horseradish peroxidase. This information was obtained by relaxation enhancements of the substrate protons and connectivities between the latter and heme 8-CH3 and a Phe residue. Manganese(II) is shown to bind to ferri-manganese peroxidase and its cyanide derivative in a specific site with a high-affinity constant (10(4) M-1). Manganese(II) binding exhibits a slow exchange rate with respect to the difference in T2(-)1 of the affected signals in the manganese(II) containing and manganese(II)-free species. Manganese(II) affects the line width of certain heme methyl resonances and of certain one-proton intensity signals in manganese peroxidase and its cyanide derivative. The behavior of MnP toward manganese(II) is compared to that of the closely related peroxidase, lignin peroxidase (LiP), with its native substrate veratryl alcohol. LiP does not have a specific binding site for manganese(II). PMID- 8504103 TI - Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy. AB - The solution structures of the recently discovered neuropeptides PACAP38 and PACAP27 have been investigated in aqueous solution containing varying amounts of trifluoroethanol (TFE) by circular dichroism (CD) spectroscopy and a combination of 2D 1H nuclear magnetic resonance (NMR) spectroscopy, distance geometry, and refined molecular dynamics and energy minimization calculations. In aqueous solution both peptides show only small transitory amounts of stable structure while in 50% TFE they adopt ordered structures. Qualitative NOE data and the use of the chemical shift index of the alpha-protons identified the positions of alpha-helical regions. A set of low-energy conformations compatible with the quantitative NOE data were obtained for both and each set were subjected to RMS analysis to determine the positions of the secondary structure elements. PACAP38 has an initial disordered N-terminal domain of eight amino acids, followed by an alpha-helical structure stretching from Ser-9 to Val-26, which contains a discontinuity between Lys-20 and Lys-21, and in the C-terminal region there is a short alpha-helix between Gly-28 and Arg-34. The structure of PACAP27 mirrors remarkably closely that of PACAP38 and shows no fraying of the C-terminal helix. The physiological significance of the three structural domains (1-8, 9-26, and 27 38) of PACAP38 is shown by a comprehensive review of recent in vitro and in vivo investigations of PACAP analogues. The correspondence of the global structural features of PACAP with other members of this family of peptides (namely, secretin, glucagon, GHRF1-29 and VIP) is demonstrated by inspection of the chemical shift indices of the alpha-protons. PMID- 8504104 TI - Intersubunit location of the active site of mammalian ornithine decarboxylase as determined by hybridization of site-directed mutants. AB - The active form of mammalian ornithine decarboxylase (ODC) is a homodimer consisting of two monomer subunits of 53 kDa each. We have used in vitro hybridization of two different catalytically inactive mutants of ODC to determine whether in the wild-type enzyme each monomer contains an independent active site or whether the active sites are shared at the interfaces between the two subunits. Two distinct mutants were obtained using oligonucleotide-directed mutagenesis: In one, cysteine-360, the major alpha-(difluoromethyl)ornithine (alpha-DFMO, a suicide inhibitor of ODC) binding site was converted to alanine. In the other, lysine-69, the pyridoxal 5'-phosphate (PLP, the cofactor of ODC) binding residue was converted to alanine. Expression of each mutant, in vitro, in reticulocyte lysate translation mix, results in the production of a completely inactive enzyme. In contrast, their coexpression restores enzymatic activity to about 25% of the wild-type enzyme. Moreover, coexpression of wild-type subunits with monomers containing both inactivating mutations reduced their activity to about 25%, while their coexpression with monomers that contain a single inactivating mutation reduced the activity to 50%. Cross-linking analysis has demonstrated that activity restoration and repression are both fully correlated with the formation of heterodimers between mutant subunits and between mutant and wild-type subunits, respectively. We therefore conclude that the active site of ODC is formed at the interface of the two monomers through the interaction of the cysteine-360-containing region of one monomer subunit with the region that contains lysine-69 of the other subunit. PMID- 8504105 TI - Binding of the substrate analogue perseitol to phosphorylated and unphosphorylated enzyme IImtl of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli. AB - Enzyme IImtl catalyzes the concomitant transport and phosphorylation of the hexitol mannitol. Here we demonstrate that the heptitol perseitol is not phosphorylated and not transported by the enzyme. However, the enzyme binds perseitol with an affinity comparable to the affinity for mannitol. Apparent affinities of the phosphorylated enzyme for perseitol were inferred from the inhibition by perseitol of mannitol phosphorylation and uptake. Apparent affinities of the unphosphorylated enzyme follow from the inhibition of mannitol binding to the enzyme. Mechanistic interpretations of the apparent inhibition constants are discussed, and it is concluded that phosphorylation of the cytoplasmic domain of enzyme IImtl has little effect on the affinity of the membrane-bound domain of the enzyme for perseitol. PMID- 8504106 TI - Aspartic acid-212 of bacteriorhodopsin is ionized in the M and N photocycle intermediates: an FTIR study on specifically 13C-labeled reconstituted purple membranes. AB - Purple membrane was regenerated from the denatured proteolytic (protease V8) fragments V-1 and V-2 of bacteriorhodopsin (BR), native membrane lipids, and all trans-retinal. FTIR difference spectra of M and N intermediates of the reconstituted system are in close correspondence to those obtained from native BR. Asp-212 is the only internal aspartic acid in the V-2 fragment (helices F and G). Reconstituting a V-2 fragment from a [4-13C]Asp-labeled BR preparation with an unmodified V-1 fragment and vice versa have allowed us to assign IR bands to either Asp-212 or any of the remaining aspartic acids on V-1 (helices A-E). A carboxylate vibration at 1392 cm-1 has been identified in the M and N intermediates and assigned to Asp-212. Since no contribution of this residue to C = O stretches of protonated carboxyl groups was detected, Asp-212 must be ionized in light-adapted BR as well. The effect of [4-13C]Asp labeling of V-1 revealed a carboxylate vibration at 1385 cm-1 in light-adapted BR. Since Asp-96 and Asp-115 are protonated, this band is caused by Asp-85. All absorption changes of C = O stretches of protonated carboxyl groups are due to Asp residues on V-1. Correspondingly, the proton acceptor for Schiff base deprotonation in M is located on V-1, and must be Asp-85 (the only ionized Asp on V-1). The band assignments are compared with those reported for BR mutants, and the potential role of Asp-212 for proton translocation is discussed. PMID- 8504107 TI - Cytosine-cytosine+ base pairing stabilizes DNA quadruplexes and cytosine methylation greatly enhances the effect. AB - Previous spectroscopic studies demonstrated that the oligodeoxynucleotide d(CGC G3 GCG) undergoes a reversible cation-dependent transition between Watson-Crick (WC) hairpin and parallel-stranded "G-DNA" quadruplex structures [Hardin, C.C., Watson, T., Corregan, M., & Bailey, C. (1992) Biochemistry 31, 833-841]. The relative stabilities of the structures were assessed as a function of pH, and it was found that the quadruplex was substantially stabilized (delta Tm = +15 degrees C) when the pH was shifted from 7.5 to 6 (apparent pKa = 6.8). In the present study, the effects of different cations and pH on four specific sequence varients were determined to test the proposal that this stabilization is due to C.C+ base pair formation mediated by N3-protonation of cytosine. Characteristically large differences in stability were observed when structures formed by d(TAT G3 ATA) and d(TAT G4 ATA) were thermally dissociated at pH 7 in the presence of different cations, verifying that Gn tracts bordered by TAT- and ATA sequences form quadruplex structures. Imino proton NMR results indicate that the d(m5C G m5C G3 G m5C G)4 and d(TAT G4 ATA)4 quadruplex structures are parallel-stranded. It was necessary to increase the K+ concentration from 40 mM to ca. 200 mM to stabilize d(TAT G3 ATA)4, while the d(TAT G4 ATA)4 complex was nearly as stable as the quadruplex formed by d(CGC G3 GCG) under the same conditions. The d(TAT G4 ATA)4 quadruplex was only slightly stabilized at pH 6 relative to pH 7.5 (delta Tm = +3 degrees C), confirming that the unique stabilization that occurs in the pH 6.8 range with [d(CGC Gn GCG)4.ionn] complexes is due to the C residues. The sequence d(m5C G m5C G3 G m5C G) was found to form a very stable quadruplex in K+ or Ca2+. As with the quadruplex formed by the unmethylated analog, the stability is greatly enhanced when the pH is decreased below about 7.2 (pKa,obs = 6.8). Dissociation kinetic constants and activation energies were determined for quadruplexes formed by d(CGC G3 GCG), d(m5C G m5C G3 G m5C G) and d(TAT G4 ATA). Quantitative comparisons showed that methylation produces a complex that is much more stable at pH 7 in 40 mM Na+ than either of the unmodified structures; the rate-limiting activation energy for dissociation of d(CGC G3 GCG)4 was 22 kcal mol-1 less than for the methylated analog.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504108 TI - Influence of DNA base sequence on the binding energetics of actinomycin D. AB - The influences of base sequence on the thermodynamic properties associated with the interaction of actinomycin D with DNA are examined. It has been previously established that GpC steps of double-helical DNAs are highly preferred binding sites for actinomycin D. In this study, a series of oligonucleotides was designed and synthesized to probe the effects of flanking base sequence (adjacent to the GpC step) and novel non-GpC binding sites on the binding of actinomycin D. The use of these oligonucleotides provides a direct method for quantitating sequence specificities and actinomycin D binding energetics. Effects of different 5' and 3' flanking nucleotides on the interactions of actinomycin with the core GpC binding sites were examined using UV-visible spectrophotometric methods, and changes in binding energetics were quantitated. These studies demonstrate strong actinomycin D binding affinities to both classical GpC and an atypical non-GpC site. Enthalpy and entropy components of the DNA binding energetics for the GpC binding sites are compared and correlated with those determined for actinomycin D binding to the high-affinity non-GpC site of an 11-mer containing TGGGT as the central sequence. This TGGGT site, first suggested to be a high-affinity sequence in our earlier photoaffinity labeling studies, exhibits binding of actinomycin D comparable in strength to that of traditional actinomycin D binding sites (i.e., GpC steps). From these studies, the overall affinity and specific thermodynamic contributions (delta H degree, delta S degree) to binding of actinomycin D are demonstrated to be highly influenced both by the sequence at the intercalation site and by neighboring bases which flank the intercalation site. PMID- 8504109 TI - Negative cooperativity in the binding of nucleotides to Escherichia coli replicative helicase DnaB protein. Interactions with fluorescent nucleotide analogs. AB - The interactions of nucleotides with Escherichia coli replicative helicase DnaB protein have been systematically studied using fluorescent nucleotide analogs, 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP), 2'(3')-O (2,4,6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP), 2'(3')-O-(2,4,6 trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP), 3'-O-(N-methylantraniloyl) 5'-diphosphate (MANT-ADP), and 1,N6-ethenoadenosine diphosphate (epsilon ADP). The binding of the analogs is accompanied by strong quenching of the protein fluorescence; 0.76 +/- 0.05, 0.76 +/- 0.05, 0.58 +/- 0.05, and 0.53 +/- 0.5 for TNP-ATP, TNP-ADP, MANT-ADP, and epsilon ADP, respectively. A thermodynamically rigorous method has been applied to obtain all binding parameters from fluorescence titration curves independent of the assumption of strict proportionality between the observed quenching of the protein fluorescence and the degree of nucleotide binding. An exact representation of the observed fluorescence quenching, as a function of the nucleotide binding, is introduced through an empirical function which enables analysis of single binding isotherms without the necessity of determining all quenching constants for different binding sites. Using this method, we determined that, at saturation, the DnaB hexamer binds six molecules of TNP-ATP, TNP-ADP, MANT-ADP, and epsilon ADP, and that there is strong heterogeneity among nucleotide binding sites. The binding isotherms are biphasic. Three molecules of nucleotide are bound in the first high affinity binding phase, and the subsequent three molecules are bound in the second low-affinity binding phase. The separation of the two binding steps is even more pronounced at higher temperatures. The change of the monitored fluorescence is sequential. The binding of the first nucleotide causes the largest quenching of the protein fluorescence with subsequent nucleotide binding inducing progressively less quenching. The simplest explanation of this behavior is that there is a negative cooperativity among nucleotide binding sites on a DnaB hexamer. The negative cooperativity is an intrinsic property of the DnaB helicase, since it is observed in the binding of nucleotide analogs which are different in type and location of the modifying group. A statistical thermodynamic model is proposed, the hexagon, which provides an excellent description of the binding process using only two interaction parameters, intrinsic binding constant K and cooperativity parameter sigma. The data suggest an important role of the phosphate groups in binding and in recognition of nucleotides by the DnaB helicase. PMID- 8504110 TI - Phosphoryl transfer between phosphorylated histidine-containing protein and histidine-containing protein is not autocatalytic. AB - Histidine-containing protein, HPr, is a phosphocarrier protein that is part of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated by enzyme I, and P-HPr transfers the phosphoryl group to the IIA domain of a number of sugar-specific enzyme II complexes. Autocatalytic phosphoryl transfer between P-HPr and HPr has recently been reported [van Dijk, A. A., Eisermann, R., Hengstenberg, W., & Robillard, G. T. (1991) Biochemistry 30, 2876-2882]. Our results show that this phosphoryl transfer is due to an unidentified contaminant of HPr preparations. The phosphoryl transfer activity is not present in all HPr preparations. When present, the phosphoryl transfer activity can be removed by further purification or destroyed over time by resuspension of HPr preparations in water. There is no autocatalytic phosphoryl transfer between P-HPr and HPr. PMID- 8504111 TI - Determination of the disulfide bridges in factor Va light chain. AB - The 74-kDa light chain of bovine factor Va is composed of three domains: the NH2 terminal A3 domain and the COOH-terminal C1 and C2 domains. In total, the light chain has eight cysteines: two in the A3 domain and three in each C domain. To determine the locations of the disulfide bridges, peptides were obtained from factor Va and iodo[1-14C]acetamide-labeled factor Va light chains by digestion with trypsin, activated protein C, lysylendopeptidase, and V8 protease. After HPLC purification, amino acid sequence and composition analyses showed that each domain of bovine Va light chain possesses a disulfide bond. The sites are Cys1684 Cys1710 (A3), Cys1866-Cys2020 (C1), and Cys2025-Cys2180 (C2). One free cysteine is located in each C domain, i.e., Cys1953 and Cys2100. The locations of the disulfide bonds in human Va and VIIIa light chains are anticipated to be similar to those of bovine Va light chain, because the cysteines involved are conserved. PMID- 8504112 TI - Characterization of the preparation process and the photochemical control of electrical properties of bilayer lipid membranes containing azobenzene chromophores. AB - We prepared photoresponsive bilayer lipid membranes (BLMs) containing azobenzene derivatives (4'-octylazobenzene-4-oxybutyric acid (AZ)) and observed the rapid and reversible changes in their electrical properties when irradiated with light. The BLMs consist of AZ (8 mol%) and glyceryl monooleate. The changes in capacitance and conductance upon irradiation by light were found to be 10 and 20%, respectively. The changes in the electrical properties of the membrane and in the structure of AZ under light irradiation were analyzed simultaneously by in situ spectroscopic, electrical and microscopic measurements. These measurements showed that the electrical changes induced by exposure to light resulted from reversible changes in the membrane structure initiated by the photoisomerization reaction of AZ. This structural change in the membrane occurred within 1 s. PMID- 8504113 TI - Monolayer characteristics of valinomycin in the presence of various salts in aqueous subphase. AB - The surface pressure-molecular area, surface potential-molecular area and Brewster reflectivity-molecular area isotherms for valinomycin monolayers (states II and III) at various aqueous salt subphases were measured. Two additional states of valinomycin monolayers were observed in the presence of K+ and Rb+ as compared to the other alkali metal cations. This phenomenon correlates with the strong complexation between the valinomycin and these cations in bulk. State II corresponds to the very special 'bangle' conformation of the polypeptide ring of valinomycin, in which all carbonyl and carboxyl groups of the amino-acid residues are coordinated to the cation inside the polypeptide ring. State III corresponds to the vertical orientation of the 'bangle' conformation of valinomycin molecules with respect to the interface. An influence of the anion size on the stability of valinomycin-cation complexes at the interface was found. PMID- 8504114 TI - Computer simulation of lipid diffusion in a two-component bilayer. The effect of adsorbing macromolecules. AB - We have modelled the effects of macromolecular adsorption upon lipid lateral diffusion in a two-component lipid bilayer or monolayer, which is at a temperature above both of the main transition temperatures. One set of lipids (binders, b) can bind to the macromolecules with a free energy of binding, FB, while the other set does not bind (non-binders, nb). We assumed that no phase separation of the lipids occurs in the absence of adsorbed macromolecules. We represented the lipid bilayer/monolayer by a triangular lattice, each site of which is occupied by a lipid molecule. Adsorbed macromolecules were represented by hexagons covering nH sites, and we defined a probability per unit of time, p, that a hexagon attempts to adsorb onto the lattice. We considered two sizes of hexagons, nH = 7 (Size-1) and nH = 19 (Size-2) and disallowed or permitted adsorbed hexagons to move laterally on the lattice. We calculate the lipid relative diffusion coefficients, Dnb, and Db, for three characteristic time regimes, (i) tau c << tau a, (ii) tau c approximately tau a and (iii) tau c >> tau a, where tau c and tau a are the times for proteins to adsorb/desorb or for lipids to move from site to site, respectively. We obtain analytical expressions for Dnb and Db in the first case and calculate them using computer simulation in the other two cases. We found that (i) D alpha (iii) < or = D alpha (ii) < or = D alpha (i) (alpha = nb, b); (ii) D alpha could display a shoulder as a function of FB for low values of p; (iii) compared to cases in which lateral diffusion was disallowed, the lateral diffusion of absorbed hexagons appeared to have little effect on Dnb, but could cause Db to increase by 50%. (iv) Scatter in the calculated values of D via simulation appeared to be largest for Size-1 hexagons, and could be understood as a consequence of the large interfacial region between areas free of hexagons and areas 'covered' by hexagons. Our results suggest that it is advisable to measure Db, since Dnb might show little change from 1.0 for the values of F and p appropriate to the system being studied. PMID- 8504115 TI - Cation-dependent leucine, alanine, and phenylalanine uptake at pH 10 in brush border membrane vesicles from larval Manduca sexta midgut. AB - Using the rapid filtration technique, cation gradient driven leucine, alanine and phenylalanine uptake by brush-border membrane vesicles (BBMV) from the highly studied model insect, Manduca sexta, is characterized at the physiological pH of 10. The vesicles are sealed and nonspecific binding is small. Almost identical initial time courses of leucine uptake are obtained whether the vesicles are osmotically balanced initially or at equilibrium. The maximum accumulation values are also similar and the equilibrium values are identical with either treatment. Equilibrium is reached by 60 min. Amino acid accumulation is cation gradient dependent and is abolished by 18 microM valinomycin. Uptake of all three amino acids occurs over a broad pH range with maximum rates at approximately pH 10 and lower rates at pH 7.5. The cation selectivity of phenylalanine and alanine uptake changes with pH; the sequence is K+ > Na+ > Cs+ >> Rb+ = Li+ at pH 10.0, whereas K+ = Na+ at pH 8.0; the selectivity of leucine uptake is K+ = Na+ > Cs+ >> Rb+ = Li+ at pH 10. Maximum K+ driven accumulation of all three amino acids decreases with anions in the order: SCN- > NO3- > Cl- = CO(3)2- = So(4)2- = HPO(4)2- > gluconate-.Vmax values are similar for all three amino acids. There are large differences in initial uptake rates (leucine > phenylalanine = alanine), and maximum accumulation values (leucine > phenylalanine > alanine). PMID- 8504116 TI - Neutral amino acid symport in larval Manduca sexta midgut brush-border membrane vesicles deduced from cation-dependent uptake of leucine, alanine, and phenylalanine. AB - Uptake of tritiated leucine, alanine, and phenylalanine was measured at the physiological pH of 10 by rapid filtration in brush-border membrane vesicles from the midgut of the larval tobacco hornworm, Manduca sexta. A 20-fold excess of unlabeled leucine, isoleucine, methionine, valine, alanine, lysine, histidine, phenylalanine, and glutamine inhibited uptake of leucine and phenylalanine, and six of these amino acids inhibited uptake of alanine, by more than 50% both in the presence and absence of a potassium ion gradient. These inhibitory amino acids also drove countertransport of leucine, alanine, and phenylalanine with accumulation ratios exceeding 2. These results are consistent with the hypothesis that leucine, alanine, and phenylalanine share a common uptake system - a broad scope B type symporter - which interacts strongly with half of the commonly occurring amino acids, interacts moderately with an additional quarter of them, but does not interact with cysteine, arginine, glutamate, aspartate, or proline. PMID- 8504117 TI - Vesamicol blocks the recovery, by recycling cholinergic electromotor synaptic vesicles, of the biophysical characteristics of the reserve population. AB - The effect of vesamicol on the ability of recycling cholinergic synaptic vesicles to recover, during a period of post-stimulation rest, the biophysical properties of the reserve pool was studied in prestimulated perfused blocks of the electric organ of the electric ray, Torpedo marmorata, a tissue rich in cholinergic synapses. The effect of the drug was analysed by high-resolution centrifugal density-gradient fractionation in a zonal rotor of the extracted vesicles. The two vesicle fractions were identified by their ATP and acetylcholine content and the recycled vesicles by their acquisition of [3H]acetylcholine derived from [3H]acetate in the perfusate. Vesamicol (10 microM) blocked the uptake of tritiated acetylcholine by recycled vesicles and also prevented them from rejoining the reserve pool. This is consistent with a previously formulated model of the recovery process, whereby the increase in the acetylcholine and ATP content of the recycled vesicles which takes place during a post-stimulus period of rest increases their osmotic load and thus their content of free water. Vesamicol, by blocking acetylcholine uptake, also blocks rehydration of the recycled vesicles and thus the accompanying decrease in their density to the value characteristic of fully charged vesicles. PMID- 8504118 TI - Alamethicin as a permeabilizing agent for measurements of Ca(2+)-dependent ATPase activity in proteoliposomes, sealed membrane vesicles, and whole cells. AB - The channel-forming antibiotic peptide alamethicin was used in measurements of Ca ATPase activity in sarcoplasmic reticulum (SR) vesicles, proteoliposomes containing Ca(2+)-ATPase from SR, and native human platelets. Alamethicin was used as a permeabilizing agent providing for a free access of the whole cells or sealed vesicles interiors for ions, ATP, and other reactants. The experiments were carried out with the use of alamethicin preparations obtained in our laboratory and that purchased from the Upjohn Company (antibiotic U-22,324). A comparative study of the effects of Ca(2+)-ionophore A23187 and alamethicin was performed on native SR vesicles containing Ca(2+)-ATPase molecules with right orientation and SR vesicles treated with cholate in order to randomize Ca(2+) ATPase molecules orientation in the membrane. It was found out that alamethicin, like A-23187, prevents the ATP-dependent Ca2+ accumulation by the vesicles and therefore activates the Ca(2+)-ATPase. Maximal specific activities of the Ca(2+) ATPase in native SR vesicles in the presence of either alamethicin, or A23187, or both of them, are equal in all cases to 20 activity units (mumol Pi per min per mg protein). The operative range of alamethicin concentrations is 5-25 micrograms/ml and is a little wider than that for A23187. The ATPase activity of the SR vesicles treated with cholate reached 20 units in the presence of alamethicin while in the presence of A23187 it was only 10 units. These data suggest that alamethicin unlike A23187 allows ATP to reach the ATPase's active centers from the inside of the SR vesicles with 'randomized' membranes, the ATP transport through the membrane not being the rate-limiting stage of ATP hydrolysis. It was shown that diffusion flux of ATP through a BLM in the presence of alamethicin may reach 10% of the flux through the hole without the BLM. With the use of alamethicin it was found out that the quality of randomization of the ATPase molecules orientation in the membrane depends on the proteoliposome preparation technique. The ATP transport through the alamethicin pores makes possible the use of alamethicin in accurate measurements of Ca(2+)-ATPase activity in whole cells. A method was developed for determination of the activity of human platelets was found to be 90-100 nmol Pi per min per mg protein. PMID- 8504119 TI - Uptake of riboflavin by intestinal basolateral membrane vesicles: a specialized carrier-mediated process. AB - The mechanism of riboflavin (RF) uptake by intestinal basolateral membrane vesicles (BLMV) was examined in this study. BLMV were isolated by an established Percoll-gradient methodology from rabbit small intestine. Uptake of riboflavin was mainly the result of transport of the substrate into an osmotically active intravesicular space with less binding to membrane surfaces. Uptake of RF with time was similar in the presence of a Na+ and a K+ gradient (out > in) and was not significantly influenced by changes in incubation buffer pH. The initial rate of uptake of riboflavin as a function of concentration was saturable in both jejunal and ileal BLMV and occurred with apparent Km values of 5.0 microM and 4.4 microM and Vmax values of 91.6 and 60.8 pmol/mg protein per 5 s, respectively. Unlabeled riboflavin and the structural analogues lumiflavin, isoriboflavin and 8 aminoriboflavin all caused significant inhibition (but to different degrees) in the uptake of [3H]riboflavin. On the other hand, 8-hydroxyriboflavin, lumichrome, lumazine and D-ribose failed to inhibit [3H]riboflavin uptake. Trans-stimulation of [3H]riboflavin efflux from preloaded BLMV by unlabeled riboflavin or lumiflavin was also observed. Altering transmembrane electrical potential by anion substitution and valinomycin-induced K+ diffusion did not affect the riboflavin uptake process. These results demonstrate the existence of a specialized carrier-mediated mechanism for riboflavin uptake by intestinal BLMV. Furthermore, the system appears to transport the vitamin by a process which is Na(+)- and pH-independent, and electroneutral in nature. PMID- 8504120 TI - CD and NMR studies on the aggregation of amphotericin-B in solution. AB - We report in this paper the aggregation properties of amphotericin-B (amp-B) in solution using CD and 1H-NMR techniques. Our results indicate that the preferred structure of amp-B in dimethylsulfoxide is a monomer at low concentrations (10( 4) M and below) and a stable dimer at higher concentrations (range 5.10(-3) M to 10(-2) M). In a DMSO/ethanol mixture (1:1 (v/v)), the antibiotic is monomeric, irrespective of the concentration within the range studied. We propose a head-to tail model based on NMR data. An understanding of the head-to-tail dimer, is, we believe important, particularly in view of the recent report wherein it is proposed that the drug inserts into bilayers as head-to-tail oligomers. PMID- 8504121 TI - The effect of ice on membrane lipid phase behaviour. AB - The effects of ice on the lipid phase behaviour of di-18:1 PE and di-18:2 PE were studied by comparing the behaviour of these lipids in supercooled and frozen dispersions. The presence of ice raised the onset temperature of the L alpha--> L beta phase transition of di-18:1 PE from -10 degrees C to -6.5 degrees C and increased its molar enthalpy from 6.1 to 8.5 kcal/mol but had little effect on the co-operativity of the transition. Real-time X-ray diffraction measurements of the HII--> L alpha phase transition of di-18:2 PE suggested that this transition could take place in the presence of ice but that the corresponding L alpha--> HII phase transition could not take place until the ice melted. Measurements of the temperature dependence of the d-spacing of di-18:1 PE and di-18:2 PC in frozen dispersions indicated that the amounts of unfrozen water in such dispersions changes significantly with temperature. It was concluded that the increases in onset temperature and molar enthalpy seen for the L alpha--> L beta transition of di-18:1 PE probably reflected the effects of osmotic dehydration. The main effect of ice in the case of the HII--> L alpha phase transition, however, appeared to be to limit the ability of the lipid to undergo structural reorganisation. PMID- 8504122 TI - Phase behaviour of membrane lipids containing polyenoic acyl chains. AB - The low-temperature thermal behaviour of di-18:2 phosphatidylethanolamine (di 18:2 PE) is shown to be characterized by similar broad low-enthalpy transitions to those previously reported for polyenoic samples of phosphatidylcholines (Keough and Kariel (1987) Biochim. Biophys. Acta 902, 11-18), and monogalactosyldiacylglycerol (Sanderson and Williams (1992) Biochim. Biophys. Acta. 1107, 77-85). Real-time X-ray diffraction measurements indicate that these transitions correspond to transitions between the gel (L beta) and liquid-crystal (L alpha) phases of the lipids. The gel phase of these lipids is, however, much more loosely packed than the corresponding phases of membrane lipids containing monoenoic or fully-saturated acyl chains. The low enthalpy and reduced co operativity of the L alpha--> L beta phase transitions of the polyenoic lipids is attributed to the reduced contribution of van der Waals interactions between their acyl chains in the gel-state of these lipids. Comparison with the earlier results obtained for MGDG suggest that the acyl chains of polyenoic lipids can form well-ordered lattices but require the additional energy input associated with the formation of a hydrogen bond network between the lipid headgroups in order to do so. PMID- 8504124 TI - The interaction of Saccharomyces cerevisiae trehalase with membranes. AB - Plasma membranes isolated from cells of Saccharomyces cerevisiae previously submitted to a heat-shock showed a 10-fold increase in membrane-bound trehalase activity. Trehalase was purified to a high specific activity and was shown to be inhibited by glucose 6-phosphate and by the addition of a neutral phospholipid like surfactant. Purified trehalase binds spontaneously to egg phosphatidylcholine small unilamellar vesicles, when in its active, phosphorylated form. When the enzyme was treated with alkaline phosphatase no binding was observed. The significance of this reversible binding for the control of trehalose metabolism in yeast cells is still unknown. PMID- 8504123 TI - A Raman spectroscopic study of acetylcholine receptor-rich membranes from Torpedo marmorata. Interaction of the receptor with carbamylcholine and (+)-tubocurarine. AB - Raman spectroscopy is used to determine structural features of alkali-treated subsynaptic membrane fragments from Torpedo marmorata electric organ, rich in native functional AcChR. Distinct vibrations attributable to the membrane proteins and lipids were identified and studied before and after addition of the agonist carbamylcholine and the competitive antagonist (+)-tubocurarine. The protein secondary structure determined by using amide-I polypeptide vibrational analysis, indicates 47% alpha-helices, 25% beta-sheets, 18% turns and 11% undefined structure. The secondary structure of the AcChR molecule was not subject to large modifications upon addition of carbamylcholine. But, the presence of the (+)-tubocurarine leads to detectable changes in the amide-I region which might be interpreted as reflecting different contributions of alpha helices and turns in the secondary structure. In addition, Raman spectra provide information about the environment of aromatic amino acids (tyrosine and tryptophan), the (C-C) bonds, the CH2 and CH3 groups of aliphatic side chains, as well as the disulfide (S-S) and cystein (C-S) bonds. The tyrosines seem 'exposed' to the aqueous medium. The Raman spectra of the AcChR-carbamylcholine complex suggest 'exposed' tryptophans, while those of the unliganded membrane-bound AcChR or of the receptor with (+)-tubocurarine are shown 'buried'. The disulfide bridges in the AcChR subunits show identical conformation in the absence and presence of carbamylcholine. On the contrary, considerable changes are found in the AcChR-(+)-tubocurarine complex. Carbamylcholine and especially (+) tubocurarine decrease lipid fluidity. PMID- 8504125 TI - Incorporation of N-acylethanolamine phospholipids into egg phosphatidylcholine vesicles: characterization and permeability properties of the binary systems. AB - We have studied the effect of the N-acylphosphatidylethanolamine (N-acylPE) on the permeability properties of liposomes composed primarily of egg phosphatidylcholine using a fluorescent anionic dye, carboxyfluorescein, as model solute. Leakage from liposomes decreased and vesicle size increased with increasing N-acylPE content. In addition, measurement of the trapped aqueous space, using the same dye marker, showed a correlation between trapped volume and vesicle size determined by dynamic light scattering. Permeability parameters were calculated according to the pseudo-first-order analysis. It appears that N-acylPE stabilizes liposomes at least in part through its ability to impart surface negative charge, in accord with the results obtained with potassium chloride as encapsulated solute. These results agreed well with osmotic response of anionic lipid vesicles. Cholesterol stabilizes N-acylPE liposomes in a proportional manner to the molar fraction of the effector. PMID- 8504126 TI - Metabolism of the 'organic osmolyte' glycerophosphorylcholine in isolated rat inner medullary collecting duct cells. I. Pathways for synthesis and degradation. AB - In isolated inner medullary collecting duct (IMCD) cells the adaptation to changes in extracellular osmolarity involves alterations in intracellular content of organic osmolytes such as glycerophosphorylcholine (GPC), sorbitol and others. To elucidate the basis of such alterations, the metabolism of GPC in IMCD cells was investigated with the labeled GPC precursor [methyl-3H]choline. The lipids phosphatidylcholine (PC), lyso PC (LPC) and sphingomyelin (SM), as well as the non lipids phosphorylcholine (Pcholine), GPC and an unknown water-soluble compound could be identified as intermediates of choline metabolism. In pulse chase experiments the radioactivity of PC expressed as specific activity was at a higher level than the other metabolites (> 10-fold after 1h). Extended chase incubations caused the specific activity of PC and LPC to decrease significantly. GPC was the only metabolite with a significant increase in specific activity under these conditions, suggesting that PC (via LPC) could be the precursor of GPC. In short-term pulse experiments the specific activity of PC and LPC was always significantly higher compared to the specific activity of GPC. Pulse chase incubations using phosphatidyl[methyl-3H]choline showed a significant decrease in specific activity of PC after 15 h accompanied by a significant increase in specific activity of LPC as well as GPC. Inhibition of the PC hydrolyzing enzyme phospholipase A2 revealed a significant increase in the specific activity of PC. For GPC, a significant decrease in the radioactive labeling could be detected. The total amount of PC decreased by 10% under these conditions whereas the amount of GPC decreased by 22% which was significantly higher because of GPC breakdown. GPC degradation was catalyzed by GPC: choline diesterase generating choline (and phosphoglycerol). Significant activity of GPC:phosphocholine diesterase could not be detected. Betaine synthesis from choline was also not present. The slowest, and probably rate-limiting reaction of GPC synthesis from choline may be the reaction of phosphocholine cytidylyltransferase generating CDP choline, since no radioactive CDP choline could be detected under any conditions. Thus, isolated IMCD cells possess the ability for the synthesis of GPC from choline via PC and LPC, as well as for the GPC degradation to choline (and phosphoglycerol). Significant experimental evidence for the occurrence of de-novo synthesis of GPC from choline or a precursor function of GPC for PC could not be detected. However, although the former possibility seems unlikely, a final proof is still lacking. PMID- 8504127 TI - Comparison of adriamycin and derivatives uptake into large unilamellar lipid vesicles in response to a membrane potential. AB - The uptake of adriamycin (ADM) and several derivatives into large unilamellar vesicles (LUV) displaying a transmembrane potential and having a lipid composition close to that of the inner mitochondrial membrane has been measured. Drug association to neutral liposomes, made of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) (70:30, w/w) was shown to be potential-dependent: in the absence of potential, accumulation of drug was almost undetectable, whereas between 11 and 50 nmol of drug/mumol phospholipid, depending on the anthracycline used, was associated to LUV exhibiting a membrane potential after 1 h incubation. Association of drugs to LUV with a lipid composition closer to that of the inner mitochondrial (cardiolipin, CL, 20%; PC 50%; PE, 30%, w/w) and displaying a membrane potential is higher than with neutral vesicles (between 40 and 76 nmol of anthracycline/mumol phospholipid after 1 h incubation). Since it is known that ADM and derivatives have a high affinity for CL, a fraction of the associated drug may bind to CL on the outer side of the vesicles. This was confirmed by the fact that, in the absence of potential, between 40 and 56 nmol of anthracycline/mumol phospholipid was still associated to LUV containing CL. In order to discriminate between drug adsorbed at the surface of the LUV and drug accumulated inside the LUV, an anthracycline fluorescence quencher (I-) was used. It was shown on neutral LUV displaying a membrane potential, that between 55 and 81% of the associated drug is actually entrapped inside the vesicles, inaccessible to the quencher. These percentages decreased to between 41 and 68%, respectively, in the presence of LUV containing CL and exhibiting a membrane potential, whereas for LUV of the same composition but displaying no membrane potential almost all the associated drug is adsorbed on the outer face of the LUV, accessible to the quencher, and likely bound to CL. This study brings evidence that antitumour anthracyclines despite important structural homologies do not accumulate to the same extent into vesicles mimicking the lipid composition and the membrane potential of mitoplasts. This ability to reach the matrix compartment of mitochondria could partly explain the differences of cardiotoxicities associated to anthracyclines with closely related molecular structure. PMID- 8504128 TI - N-acylethanolamines as membrane topological stress compromising agents. AB - The effect of different N-acylethanolamines on the phase behaviour of fully hydrated egg phosphatidylethanolamines is reported. In particular, in the presence of N-acylethanolamines, the transition from the liquid-crystalline lamellar (L alpha) to the inverse hexagonal (HII) phase is observed at higher temperature with respect to the temperature transition of pure phosphatidylethanolamine. Moreover, in correspondence of this transition, an intermediate Q224 (space group Pn3m) cubic phase has been detected. Since the structure of this cubic phase presents unique topological analogies with the lipid bilayer organization, these data suggest the possible role of N acylethanolamines in stabilizing the biological membranes by avoiding a sudden change to a non-bilayer phase in those tissues which undergo stress conditions. PMID- 8504129 TI - Gene amplification and tumor progression. AB - Proto-oncogenes are the genes which are most frequently found amplified in human tumor cells. Acquisition of a drug-resistant phenotype by gene amplification is frequent for in-vitro cultured cells but is very rare in human tumors. Proto oncogenes amplified in human tumors belong essentially to one of three families (erbB, ras, myc) or to the 11q13 locus. Amplification is always specific for the tumor cells and is not found in constitutional DNA of the patient, indicating that amplification of the gene is selected for during tumor growth. For genes of the first three families, amplification results in overexpression in most of the cases. These are strong arguments in favor of a role of this amplification in tumor progression. The gene whose overexpression is the driving force for the selection of the amplification of the 11q13 locus is not known. The prad1 gene is presently a good candidate. Amplification of one type of proto-oncogene is generally not restricted to one tumor type. However, the N-myc gene is amplified mainly in tumors of neuronal or neuroendocrine origin and L-myc amplification is restricted to lung carcinomas. To understand the role of proto-oncogene amplification and overexpression in tumor progression it is necessary to know the function of the corresponding protein in the cell. erbB proteins are transmembrane receptors for growth factors. ras genes encode small GTP-binding proteins which are possibly involved in signal transduction. The myc proteins are transcription factors. The expression of the c-myc gene is induced a few hours after cells of various types have been induced to proliferate. The genes of these three families therefore encode proteins which appear to be involved in signal transduction. It is possible that overexpression of one of them, as a result of gene amplification, makes the cell a better responder to low levels of growth stimuli. For several genes which are found amplified in human tumors, it was shown that overexpression of the normal protein could confer a transformed or tumorigenic phenotype to in-vitro cultured cells. In addition, several studies on animal and human tumor-derived cell lines with an amplified proto-oncogene have established a relationship between proto-oncogene amplification and the tumorigenic phenotype. In neuroblastomas, it was proposed that down-modulation of MHC Class I antigens is a consequence of N-myc amplification and that this could be important in the progression toward a metastatic phenotype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504130 TI - Molecular characterization of the retinoblastoma susceptibility gene. AB - Retinoblastoma is recognized as a hereditary cancer. Genetic and epidemiological analysis of the disease has been incorporated into a two-hit mutational inactivation hypothesis of the origin of retinoblastoma. The molecular cloning and characterization of the retinoblastoma gene and gene product has allowed a critical testing of this two-hit hypothesis. All the predications of the model have been born out by experiment so far. These include inheritance of one mutated RB allele as the origin of hereditary retinoblastoma, subsequent loss of the remaining allele upon tumorigenesis, the involvement of the same RB gene in both sporadic and hereditary retinoblastoma, the somatic mutation of both RB alleles in sporadic retinoblastoma, the lack of RB expression in any retinoblastoma yet examined, and the recessiveness of mutated RB alleles. The RB gene exhibits functional properties consistent with its role as a suppressor of tumor formation. For example, re-expression of RB in tumor cells lacking endogenous RB leads to a loss of tumorigenic properties. RB protein can also inhibit progression through the cell division cycle, and it physically and/or functionally interacts with important cell cycle regulatory molecules. Although confirmation of the two-hit hypothesis seems complete, we can not rule out the possibility that other genes are involved in the genesis of this tumor. For example, there seems to be variable resistance to tumor development even in patients inheriting retinoblastoma susceptibility. Further, heterozygous RB null mice do not develop retinoblastoma, but develop a characteristic brain tumor instead. The molecular isolation of the RB gene is an important achievement in research on cancer. For the first time, it has become possible to examine, at the molecular level, genes that inhibit the growth of tumor cells. The precise mechanism of action of RB is unknown, but a broad outline is beginning to emerge. RB seems to negatively influence tumor cell growth by participating in regulation of the cell division cycle. RB has also been implicated in differentiation; its effect on the cell division cycle and its effects on differentiation may be different manifestations of the same function. Since RB is involved in oncogenesis, gene regulation, and cellular differentiation, it is obviously an attractive gene for intense study; understanding the function and mechanism of action of RB will impact the understanding of many, important cell processes. PMID- 8504131 TI - Cyclins and oncogenesis. PMID- 8504132 TI - Posttranslational processing of the ras superfamily of small GTP-binding proteins. PMID- 8504133 TI - Structures and functions of the K rev-1 transformation suppressor gene and its relatives. PMID- 8504134 TI - Molecular species composition of glycerophospholipids in rat sciatic nerve and its alteration in streptozotocin-induced diabetes. AB - The molecular species composition of glycerophospholipid classes in nerves of normal and experimentally diabetic rats was determined. sn-1,2-Diacylglycerol (DAG) moieties of purified phospholipids were liberated enzymatically and analyzed as the benzoate derivatives by high-performance liquid chromatography. The most abundant molecular species in phosphatidylinositol (PI) from normal nerve were 18:0/20:4 (54%) and 16:0/18:1 (17%), whereas in phosphatidylcholine (PC), 16:0/18:1 (52%), 16:0/16:0 (12%) and 18:0/18:1 (11%) predominated. In phosphatidylethanolamine and ethanolamine plasmalogen, 18:1/18:1, 16:0/18:1 and 18:0/18:1 comprised more than 60% and 75% of the molecular species, respectively. Phosphatidylserine was characterized by a high content of 18:0/18:1 (38%) and a relative abundance of the 18:1/20:0, 18:1/22:0 and 18:1/24:0 molecular species, which together accounted for over 30% of the total. The molecular species profile of phosphatidic acid did not closely resemble that of any other phospholipids or DAG. In diabetic nerve, the molecular species composition of all diacylphospholipids showed a significant decline in the content of one or more arachidonoyl-containing molecular species. The largest decline occurred in PC and the least in PI. Except in PC, 16:0/20:4 was more depressed than 18:0/20:4. In combination with previous analyses of DAG molecular species which showed a similar decline in the content of arachidonoyl-containing molecular species in nerve from experimentally diabetic rats (Zhu, X. and Eichberg, J. (1990) J. Neurochem. 55, 1087-1090), the results suggest that nerve DAG arises largely, but not entirely, from phosphoinositides and that PC could be a significant precursor, especially in diabetic nerve. PMID- 8504135 TI - The effect of retinoids and clofibric acid on the peroxisomal oxidation of palmitic acid and of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid in rat and rabbit hepatocytes. AB - The effects of retinoids and the peroxisome proliferator clofibric acid on peroxisomal enzyme pathways were studied in hepatocytes from both rat and rabbit. Retinoic acid and retinol increased the activity of acyl-CoA oxidase in rabbit hepatocytes around 60% and around 30% in rat hepatocytes. Exposure to clofibric acid caused an increase in acyl-CoA oxidase activity of 115% in rat hepatocytes and of 40% in rabbit hepatocytes, indicating that rabbit is less sensitive to peroxisome proliferator than rat. Simultaneous exposure to clofibric acid and retinoids did not act additatively or synergistically. Both rabbit and rat hepatocytes expressed mRNA for the peroxisome proliferator activated receptor, (PPAR), although the transcript in rabbit was slightly smaller compared to that expressed in rat hepatocytes. The effect of retinoic acid in 7800 C1 Morris rat hepatoma cells, a cell line known to have an inducible peroxisomal beta-oxidation of fatty acids, was only slight with an increase of the acyl-CoA oxidase activity of 25% compared with control cells. As for clofibric acid, which gave a 2-fold induction of the acyl-CoA oxidase activity, the effect of retinoic acid was potentiated by dexamethasone. These cells also expressed mRNA for PPAR, with the same size as that found in rat hepatocytes. The oxidation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA), an intermediate in bile acid formation, in rat hepatocytes increased 110% by clofibric acid and around 80% by retinoic acid. In rabbit hepatocytes, clofibric acid increased the oxidation rate 75% and retinoic acid 100%. The results presented here show similarities in the effects of retinoids and clofibric acid on the acyl-CoA oxidase activity and the oxidation rate of THCA, since they increase these two peroxisomal activities in hepatocytes in vitro. A decrease in both these enzyme activities occurs during cultivation time in untreated primary hepatocyte cultures. The present data may therefore either be explained by an increased expression or an induced stability of the enzymes involved. PMID- 8504136 TI - Phospholipase A2 activity and exocytosis of the ram sperm acrosome: regulation by bivalent cations. AB - Previous work has shown that the sequence leading to exocytosis of the sperm acrosome involves at least three Ca(2+)-requiring processes, the first one probably represented by breakdown of the polyphosphoinositides and the final one by membrane fusion. We have investigated whether phospholipase A2 (PLA2) represents the intermediate Ca(2+)-requiring event by stimulating ram spermatozoa with the ionophore A23187 and various bivalent cations. Spermatozoa prelabelled with [14C]arachidonic acid and treated with ionophore and millimolar Ca2+ showed a considerable release of arachidonic acid; parallel sperm samples similarly treated underwent acrosomal exocytosis. Mn2+ was capable of completely substituting for Ca2+, even if residual Ca2+ in the system was chelated with EGTA: both arachidonic acid release and acrosomal exocytosis took place after treatment with A23187, EGTA and Mn2+. Neither Mg2+ nor Ba2+ promoted arachidonic acid release or exocytosis. The effects of Sr2+ were more complex and allowed us to probe the sequence of events leading to membrane fusion. Both arachidonic acid release and exocytosis occurred after treatment with A23187 and Sr2+ but none of these responses were seen if EGTA was also included. These results suggest that residual micromolar Ca2+ is either needed for Sr2+ to fully promote PLA2 activity, or that micromolar Ca2+ is needed for one or more upstream events that may in turn serve to activate PLA2. Evidence for or against the first possibility was sought by examining PLA2 activity in sperm sonicates. Enzyme activity was maximal in the presence of any bivalent cation and it was not reduced (in the case of Sr2+) or only reduced slightly (Mg2+, Mn2+, Ba2+) if residual Ca2+ was chelated with EGTA; this indicates that Sr2+ can promote PLA2 activity in the total absence of Ca2+. The second possibility was explored by treating spermatozoa with A23187 for 5 min (to allow for complete phosphoinositide breakdown; Roldan and Harrison (1989) Biochem. J. 259, 397-406), and then adding EGTA and Sr2+. This resulted in neither arachidonic acid release nor exocytosis, thus indicating that another as yet unidentified Ca(2+)-dependent event may occur before PLA2 activation. PMID- 8504137 TI - Effect of human native low-density and high-density lipoproteins on prostaglandin production by mouse macrophage cell line P388D1: possible implications in pathogenesis of atherosclerosis. AB - Macrophages have been shown to play a key-role in the development of atherosclerotic lesions. Monocyte attraction and activation in the arterial wall lead to foam cell formation, cholesterol accumulation and secretion of inflammation mediators. Among macrophage secretions, prostacyclin and thromboxane are prostaglandins involved in the regulation of coagulation and vascular permeability. In this study, we have evaluated the effects of human native low density and high-density lipoproteins on macrophage prostaglandin production (P388D1 mouse cell line). Lipoprotein fractions were purified from venous blood of healthy volunteers by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and prostaglandins quantified by high-performance liquid chromatography. Our technique allows the determination of the main classes of prostaglandins. In the presence of low-density lipoproteins, time-course study showed an increase in total prostaglandin production within 10 min (50 times basal secretion level). This increase was dose dependent. A steady-state was obtained at 20 mg protein LDL/1. Stimulation of thromboxane B2 and prostacyclin was predominant, with a main effect on the proaggregant thromboxane. Production of the proinflammatory PGF2 alpha and the immunoregulatory PGE2 was lower. In the presence of high-density lipoproteins, P388D1 cells also increased their total prostaglandin secretion at 30 min, in a dose-dependent manner. This increase was directly related to a stimulation of prostacyclin, with no significant effect on thromboxane. Our results demonstrate that normal low-density lipoproteins can stimulate macrophage prostaglandin secretions, with putative deleterious effects on the arterial wall, in particular thrombus formation. On the other hand, high-density lipoproteins, by mainly stimulating prostacyclin, could theoretically have a beneficial influence. PMID- 8504138 TI - Quantification of the interaction of lysolecithin with phosphatidylcholine vesicles using bovine serum albumin: relevance to the activation of phospholipase A2. AB - The activity of soluble phospholipase A2 to hydrolyze phosphatidylcholine vesicles increases abruptly after a lag time of several minutes. The onset of this apparent activation event probably results from the accumulation of a threshold mole fraction of the hydrolysis products (lysolecithin and fatty acid) in the bilayer. One important observation relevant to the mechanism of this activation process is the biphasic dependence of the lag time on vesicle concentration. To test whether this dependence can be attributed entirely to the strength of partitioning of the lysolecithin into the phosphatidylcholine bilayer, we estimated the apparent partition coefficient of lysophospholipid in the membrane of phosphatidylcholine vesicles. Based on competition between bovine serum albumin and the vesicles for the lysophospholipid, we estimated the partition coefficient to be about 5.10(-7) for palmitoyl lipids at 39 degrees C and about 9.10(-7) for myristoyl lipids at 22 degrees C. These values were able to rationalize the behavior of the lag time with dipalmitoylphosphatidylcholine vesicles, but they were unable to predict the behavior with dimyristoylphosphatidylcholine. Therefore, it appears that the complete dependence of the lag phase on vesicle concentration must be explained by additional means such as the possible contribution of nascent fatty acid or previously proposed kinetic activation mechanisms. PMID- 8504139 TI - Catalytic properties of rabbit kidney fatty acid omega-hydroxylase cytochrome P 450ka2 (CYP4A7). AB - We have examined in detail the substrate specificity of a rabbit kidney fatty acid omega-hydroxylase, designated cytochrome P-450ka2 (CYP4A7). The hydroxylation products were identified as omega- and (omega - 1)-hydroxy fatty acids mainly using gas chromatography-electron impact mass spectrometry. [1] Straight-chain saturated fatty acids ranging from 10 to 19 carbons were effectively hydroxylated at the omega- and (omega - 1)-position. The ratios of omega- to (omega - 1)-hydroxylation activity decreased with increasing the carbon chain length of fatty acids. [2] Both isomyristate and anteisomyristate, and isopalmitate were hydroxylated several fold more rapidly than myristate and palmitate, respectively, with iso-branched chain fatty acids being hydroxylated at the omega-position solely. [3] Both palmitoleate and palmitoelaidate, and both oleate and elaidate were hydroxylated much more rapidly than palmitate and stearate, respectively. [4] Linoleate, gamma-linolenate, and arachidonate were also excellent substrates for this enzyme. [5] Prostaglandin (PG) A1 and PGA2 were efficiently hydroxylated at the omega-position solely, with PGE1 and PGE2 being much less active. [6] Arachidonic acid not only showed a Km value significantly lower than those for lauric acid, gamma-linolenic acid and PGA1, but also it is a potent competitor for lauric acid and PGA1, showing a very high affinity for the enzyme. It is possible that arachidonic acid is the physiological substrate for kidney P-450ka2. PMID- 8504140 TI - Detection of arachidonoyl-selective phospholipase A2 in human neutrophil cytosol. AB - The present report describes the presence of an arachidonic-acid-selective, dithiothreitol-insensitive phospholipase A2 enzyme activity in human neutrophil cytosol. The enzyme activity is eluted from Mono Q FPLC column between 350 to 450 mM salt and translocates from cytosol to membrane in a calcium dependent fashion. Furthermore, the PLA2 activity in the cytosol is quantitatively precipitated by the antibodies against U937 cPLA2. The neutrophil enzyme also migrates as approximately 110 kDa protein on SDS polyacrylamide gels. These studies indicate that the PLA2 enzyme present in human neutrophil cytosol is identical to the previously reported U937 cPLA2 (Clark et al. (1990) Proc. Natl. Acad. Sci. USA 87, 7708 and Clark et al. (1991) Cell 65, 1043). PMID- 8504141 TI - An inhibitor of squalene epoxidase, NB-598, suppresses the secretion of cholesterol and triacylglycerol and simultaneously reduces apolipoprotein B in HepG2 cells. AB - NB-598, a specific inhibitor of squalene epoxidase, suppressed the secretion of cholesterol and triacylglycerol from HepG2 cells into the medium. L-654,969, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibited the secretion of cholesterol as potently as NB-598, but did not suppress the secretion of triacylglycerol. Both compounds decreased the intracellular cholesterol content almost equally, and neither of the compounds reduced the intracellular triacylglycerol content. The suppression of lipid secretion by NB 598 was associated with a significant reduction in apolipoprotein (apo) B secretion into the medium. Therefore, the suppression of lipid secretion by NB 598 may be caused by a reduction in the number of triacylglycerol-rich lipoprotein particles. In contrast, the suppression of cholesterol secretion by L 654,969 may be due to a modulation of lipoprotein lipid composition, since this agent did not reduce the secretion of apo B or triacylglycerol. The secretion of apo A-I was unaffected by either NB-598 or L-654,969. Pulse chase studies using [35S]methionine showed that the suppression of apo B secretion by NB-598 depended on an enhancement of intracellular degradation of apo B. These results indicate that the secretion of apo B from HepG2 cells is not regulated by the lipid synthesis alone, and suggest that the mechanism of the hypolipidemic effect of NB 598 involves the suppression of triacylglycerol-rich lipoprotein secretion from the liver as well as an inhibition of cholesterol synthesis in the liver. PMID- 8504142 TI - Dietary lipids coinduce xenobiotic metabolizing enzymes in rat liver. AB - We examined the role of dietary lipids in regulating the activities and amounts of epoxide hydrolase, UDP-glucuronosyltransferase and glutathione S-transferase in rat liver. Male Wistar rats were fed a fat-free (FF) diet or isocaloric control diet containing 5% corn oil (CO) or 5% fish oil (FO) for 3 weeks. The activities of these enzymes were approx. 2-fold higher in rats fed the FO diet vs. the FF diet. Intermediate levels of enzyme activity were found in rats fed the CO diet. Diet-induced differences in enzyme levels were shown by immunoblotting. The highest levels of epoxide hydrolase, UDP glucuronosyltransferase and glutathione S-transferase were detected in rats fed the FO diet. The lowest levels of these enzymes were found in rats fed the FF diet. Intermediate levels of enzyme were found in rats fed the CO diet. Thus, diet-induced differences in enzyme activities were paralleled by changes in enzyme levels. Fatty acid analysis of microsomal lipids showed that the FF diet was associated with decreased levels of n-6 fatty acids vs. the CO diet. The FO diet resulted in increased levels of n-3 fatty acids vs. the other diets. PMID- 8504143 TI - The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. AB - Enteral absorption by healthy male volunteers of cis-5,8,11,14,17 eicosapentaenoic acid (20:5(n-3), EPA) and cis-4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3), DHA) from an ethyl ester enriched in EPA and DHA (K85) and from natural fish oil (TG30) was found to be similar after intake of equivalent doses. Thus, after administration twice daily for 14 days, the amounts of EPA and DHA in total serum lipids and in serum phospholipids were essentially identical for the two ester forms of the n-3 fatty acids. A dose-dependent relationship between intake and total phospholipid serum levels was observed for EPA, which increased 6.5-12-fold and 4.8-9-fold, respectively, but DHA reached a plateau at 2-2.5-fold over the control after supplementation. Arachidonic acid (AA) did not change significantly in total serum lipids, but fell 10-20% in serum phospholipids. The supplementation resulted in a 6.3-11-fold increase in the EPA/AA ratio. A significant and dose-dependent 25-45% reduction in linoleic acid (18:2(n-6), LA) was found in serum phospholipids, while a smaller decrease was observed in total serum lipids. 20:3(n-6), 20:3(n-9) and 22:5(n-6) also decreased significantly in serum phospholipids. Saturated fatty acids remained essentially unchanged. Some 35-47% decrease in serum triacylglycerols and approx. 10% decrease in cholesterol levels were also observed. In spite of the similar serum levels of EPA and DHA obtained in vivo, in vitro hydrolysis by porcine pancreatic lipase of K85 was 3 fold slower than hydrolysis of a glyceryl ester (TG85) similarly enriched in EPA and DHA, and 15-fold slower than the hydrolysis of the 3-fold less enriched TG30 with EPA and DHA predominantly in the 2-position. Under similar conditions release of AA from glyceryl ester and ethyl ester was essentially similar and approx. 1.5-fold faster than release of EPA and DHA from ethyl esters. In vitro hydrolysis of olive oil was 1.8-fold faster than hydrolysis of a natural fish oil (TG30) under similar conditions. Thus, the order of the rates of hydrolyses was olive oil > TG30 > TG85 > triarachidonin > LA ethyl ester > AA ethyl ester > ethyl ester K85. Our results show that in spite of differences in the rate of hydrolysis by lipase in vitro, the enteral absorption of EPA and DHA is as least as good from a synthetic ethyl ester highly enriched in EPA and DHA as it is from a natural triacylglycerol containing equivalent amounts of these fatty acids. PMID- 8504144 TI - Biosynthesis of 8R-hydroperoxylinoleic acid by the fungus Laetisaria arvalis. AB - 8-Hydroxylinoleic acid is known to be a fungicidal metabolite formed by the fungus Laetisaria arvalis (Bowers, W.S. et al. (1986) Science 232, 105-106). In the present report, the mechanism of formation of 8-hydroxylinoleic acid was investigated. L. arvalis metabolized [14C]linoleic acid to 8-hydroperoxylinoleic acid and 8-hydroxylinoleic acid as major metabolites. The identification is based on the reduction of the hydroperoxide to an alcohol with stannous chloride and gas chromatography-mass spectrometry. The absolute configuration of the hydroxyl was determined to be R by ozonolysis of the (-)-menthoxycarbonyl derivative of 8 hydroxylinoleic acid. Linoleic acid 8R-dioxygenase activity was present in the 100,000 x g supernatant of the cell lysate. In summary, the 8R-linoleic acid dioxygenase of L. arvalis shows many similarities with the 8R-dioxygenase recently described in the fungus Gaeumannomyces graminis. PMID- 8504145 TI - Bacterial expression, purification and partial characterization of recombinant rabbit reticulocyte 15-lipoxygenase. AB - The recombinant rabbit reticulocyte 15-lipoxygenase has been expressed in E. coli with a yield of about 50-70 micrograms pure lipoxygenase protein per 1 of liquid culture. The enzyme has been purified to apparent homogeneity from the bacteria lysis supernatant by ammonium sulfate precipitation, and two consecutive steps of anion exchange chromatography on a Mono Q column. As the native enzyme the recombinant lipoxygenase has a molecular mass of 75 kDa, an isoelectric point of 5.5 and oxygenates both linoleic acid (formation of 13S-hydroperoxy-9Z,13E octadecadienoic acid) and arachidonic acid. With the latter substrate it exhibits a dual positional specificity (formation of 15S-hydroperoxy-5Z,8Z,11Z,13E eicosatetranoic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid in a ratio of 12:1). Furthermore, the enzyme is capable of oxygenating biomembranes, as indicated by HPLC analysis of esterified oxygenated polyenoic fatty acids. PMID- 8504146 TI - Biosynthesis of eukaryotic lipid molecular species by the cyanobacterium Spirulina platensis. AB - This report brings evidence that a prokaryotic photosynthetic organism can synthesize eukaryotic molecular species of glycerolipids. When Spirulina platensis PCC 8005 was supplemented with oleic acid, the sum of the percentages of 18 carbon (C18) fatty acids in monogalactosyldiacylglycerol (MGDG), the major lipid class, became largely higher than 50 mol%. This was absolutely unexpected from the well-known structure of cyanobacterial lipids. In these organisms, C18 fatty acids usually account for less than 50 mol% because they are esterified on carbon 1 of the glycerol, exclusively. This classical feature was 99% confirmed in control as well as in palmitate-supplemented cultures. The major molecular species of MGDG, which resulted from the different distributions of fatty acids on carbons 1 and 2 of glycerol, were C18/C16 type, belonging to the so-called "prokaryotic" type of lipids. By contrast, the molecular species of MGDG from oleate-supplemented cultures consisted of only 74 mol% of C18/C16 and the complementary 26 mol% were C18/C18, the so-called "eukaryotic" type of lipids. Furthermore, such C18/C18 lipids were also evidenced as traces (< 1%) in control cultures. These results underline the fact that the fatty acid specificity of 1 monoacylglycerol-3-phosphate-acyltransferase (in Spirulina) is not as absolute as the widely accepted concept of prokaryotic lipid would suggest. Oleate, supplemented at high concentration, can be compelled to act as a substrate for the acyltransferase and this results in the appearance of C18/C18 "eukaryotic" lipids in a prokaryotic organism. PMID- 8504147 TI - Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV)-infected cell lines. AB - Glycolipid compositions of cells infected by human retroviruses (human immunodeficiency virus, HIV and/or human T-cell lymphotropic virus type I, HTLV I) have been studied. Eight cell lines, comprising two HTLV-I-infected T-cell lines (MT-2 and MT-4), two HTLV-I-negative T-cell lines (Jurkat and MF), a macrophage cell line (U937), and three HIV-infected counterpart cell lines (MT 4/HIV, Jurkat/HIV and U937/HIV) were used. The neutral glycolipids and gangliosides isolated from these cell lines were compared. Among them, the HTLV-I infected T-cell lines, MT-2 and MT-4, showed similar patterns for both neutral glycolipids and gangliosides. Neutral glycolipids (GlcCer and LacCer) of MT-2 and MT-4 cells were markedly decreased, and a ganglioside, GM3, of theirs was decreased to only a trace amount compared to that in other cell lines. Gangliosides of MT-4 and MT-4/HIV were further separated on an Iatrobeads column, and were identified as GM2, GM1a and GD1a by methylation and liquid secondary ion mass spectrometric analyses. Since the patterns of neutral glycolipids and gangliosides of MT-2 and MT-4 are unique, as compared to those of HTLV-I-negative cells, it is suggested that these changes are related to HTLV-1 infection. No prominent differences in the ganglioside compositions between HIV-infected and non-infected cell lines could be observed. But it is noteworthy that the contents of asialo-GM2 in Jurkat/HIV and MT-4/HIV cells were increased as compared to those in the parental cell lines. PMID- 8504148 TI - Activation of plasma lysolecithin acyltransferase reaction by apolipoproteins A I, C-I and E. AB - The lysolecithin acyltransferase (LAT) activity of lecithin-cholesterol acyltransferase (LCAT) converts lysophosphatidylcholine (lyso PC) to PC, and requires low-density lipoproteins (LDL). To determine whether LDL can be replaced by defined substrates, we tested proteoliposomes containing egg PC, labeled lyso PC and apoprotein (apo) A-I at molar ratios of 250:12.5:0.8, as substrate for purified enzyme. A significant percent of lyso PC in this substrate was acylated to PC, indicating that apo A-I can substitute for apo B in LAT reaction, and that PC is the acyl donor in the reaction. Apo C-I and apo E were, respectively, 70% and 40% as effective as apo A-I. When both lyso PC and free cholesterol (FC) were incorporated into the same proteoliposome, they competed with each other for the acyl groups, with 72% of the total acylation being directed to FC and 28% to lyso PC, at equimolar concentrations. With the native lipoproteins, the esterification of lyso PC was dominant in LDL, whereas FC esterification was dominant in high density lipoproteins (HDL). Albumin inhibited LAT and activated LCAT in both lipoproteins, but its effects were more pronounced in HDL. These results indicate that the esterification of lyso PC and FC involve the same mechanism, and that the relative predominance of LAT on LDL is due to higher affinity of lyso PC to LDL, compared to HDL. PMID- 8504149 TI - Dietary vitamin A modulates lecithin-retinol acyltransferase activity in developing chick intestine. AB - Retinol absorbed and generated from beta-carotene requires to be esterified by lecithin-retinol acyltransferase (LRAT) in intestinal absorptive cells. To characterize developmental changes in retinol absorptive capability in intestine, we determined LRAT activity and the amount of its retinol donor, cellular retinol binding protein, type two (CRBP(II)) in the duodenum of developing chicks. The LRAT activity in duodenal microsomes was very low at 18- and 20-day chick embryo, but exhibited a rapid (15-fold) increase during 48 h around hatching, which occurred in parallel with the abrupt elevation of the content of CRBP(II) in chick duodenum. To examine whether dietary vitamin A affects the developmental change in LRAT activity and CRBP(II) content, 1-day-old chicks were pair-fed vitamin A-depleted or vitamin A-supplemented diet for 14 days. The chicks fed vitamin A-depleted diet showed significantly reduced LRAT activity and CRBP(II) in duodenum as early as 3 days after the start of the vitamin A-depleted diet. Changing the diet from vitamin A-depleted to vitamin A-supplemented diet led to an increase in duodenal LRAT activity within 24 h, while serum retinol concentration remained unchanged. These results suggest that duodenal LRAT activity and CRBP(II) are modulated by dietary vitamin A during the perinatal period. PMID- 8504150 TI - Injury to the arterial wall of rabbits produces proteoglycan variants with enhanced low-density lipoprotein-binding property. AB - The effect of arterial injury on proteoglycans (PG) and their ability to bind low density lipoprotein (LDL) were studied in rabbits 12 weeks after balloon injury. Following biosynthetic labeling in an organ culture system, PG were isolated under dissociative conditions from deendothelialized areas (DEA), reendothelialized areas (REA), and uninjured areas (control) of the aortic tissue. DEA and REA tissues yielded 42-52% more PG and incorporated 39-67% more 35S-label into proteoglycans than control tissues. Ion-exchange chromatography of PG from DEA and REA tissues yielded PG-I, PG-II, and PG-III, while from control tissue only PG-I and PG-II. PG-II formed major portion (74-84%) of the isolated PG in all three tissue types. PGI preparations comprised entirely of heparan sulfate (HS)-PG of similar hydrodynamic size (Kav = 0.45-0.47). PG-II from DEA and REA tissues consisted of PGII-A (Kav = 0.02-0.04) and PGII-B (Kav = 0.32), while PG-II from control tissue contained only PGII-B with relatively smaller hydrodynamic size (Kav = 0.40). PGII-A preparations contained predominantly chondroitin sulfate (CS)-PG with no dermatan sulfate (DS); whereas PGII-B consisted mainly of CS/DS-PG, with relatively high proportion of DS in DEA and REA tissues vs. control tissue (50-54% vs. 43%). Further, the glycosaminoglycan chains of CS/DS-PG from DEA and REA tissues were 1.7-fold longer than those from control tissue. PG-III contained about 80% CS/DS-PG and 20% HS-PG; CS/DS-PG was similar to those found in PGII-B from DEA and REA tissues. HS-PG from PG-II and PG-III, unlike those from PG-I, was enriched with N-sulfated residues. PGI from all the three tissue types bound poorly to LDL. On the other hand, PGII-A, PGII B, and PG-III from DEA and REA tissues showed enhanced ability to bind LDL, in that order. For example, the LDL-binding ability of PGII-B from DEA and REA was 2.9- to 3.1-fold above that from control tissue. Thus, arterial injury with or without regenerated endothelium produces proteoglycan variants with altered characteristics and enhanced LDL-binding ability. PMID- 8504151 TI - Limited metabolic interaction of serine with ethanolamine and choline in the turnover of phosphatidylserine, phosphatidylethanolamine and plasmalogens in cultured glioma cells. AB - Modulation of choline phosphoglyceride turnover has been investigated extensively but less is known about regulation of serine and ethanolamine phosphoglyceride synthesis and turnover. We investigated incorporation and interactions of [3H(G)]L-serine, [1,2-14C]ethanolamine and [methyl-3H]choline in cultured glioma cells. Exogenous serine did not compete with ethanolamine or choline incorporation and did not chase labeled headgroup from ethanolamine phosphoglycerides (PE); serine displaced headgroup of prelabeled phosphatidylserine (PtdSer) resulting in less labeled PtdSer for decarboxylation. In contrast, exogenous ethanolamine markedly chased labeled headgroup of non plasmenylethanolamine phosphoglycerides (NP-PE) with less effect on plasmalogen (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) whether headgroup was derived from [3H]serine or [14C]ethanolamine. Label in chase medium was mainly ethanolamine to 12 h; phosphoethanolamine was present with longer chase (12-48 h). Choline did not compete with serine incorporation and had little chase effect on PtdSer and PE. Choline and ethanolamine competitively interacted with preference for choline. These data suggest that (1) PtdSer synthesis in cultured glioma cells may involve more than headgroup exchange; (2) PE turnover with metabolite release to medium may involve both phospholipase D and phospholipase C; (3) acceleration of PE turnover by exogenous ethanolamine primarily involves NP-PE with lesser involvement of plasmalogen; and (4) in contrast to lack of interaction between serine and other headgroup precursors, choline and ethanolamine compete primarily at uptake. PMID- 8504152 TI - Inhibitory effect of melanin precursors on arachidonic acid peroxidation. AB - A possible role of melanin precursors in lipid peroxidation was investigated using the lipoxygenase catalysed oxygenation of arachidonic acid (AA) as a model system. Polarographical monitoring of oxygen consumption showed that, among the metabolites examined, 5,6-dihydroxyindole (DHI) was the most active in inhibiting AA oxygenation catalysed by 15-lipoxygenase. The inhibition was found to be concentration-dependent with an IC50 value of 15 microM. Similar effects were observed in the case of the 5-lipoxygenase promoted reaction. Periodical HPLC analysis of the oxidation mixture showed that, in the presence of DHI, the rate of substrate consumption is markedly reduced. The inhibitory potency was significantly increased either by preincubation of DHI with the enzyme or by increasing the time of residence of the indole in aerated buffer solutions prior to contact with the enzyme. Addition of catalase to the incubation mixture resulted in a partial removal of DHI inhibition. From these and other experiments, an inhibition mechanism is proposed which involves inactivation of the enzyme by reactive species, especially hydrogen peroxide, arising from DHI autoxidation. PMID- 8504153 TI - Purification and properties of a lipase from Penicillium expansum. AB - Penicillum expansum DSM 1994 produces a new, inducible extracellular lipase when grown in medium containing 0.1% olive oil. Maximum activity was obtained after 4 days of incubation at 20 degrees C. The enzyme was purified 219-fold by cross flow filtration, ammonium sulfate precipitation and hydrophobic interaction chromatography to a final specific activity of 558 U/mg. The molecular weight of the homogeneous lipase was (25 kDa) determined by gel filtration and SDS-PAGE, however, it forms active dimers and higher aggregates as observed after native PAGE. The enzyme was identified as a glycoprotein with a pI of 5.5. The N terminal sequence shows a homology to sequences of other lipase just behind their consensus sequence. Enzyme stability was enhanced by the addition of Tween 20 and Lubrol PX. The enzyme showed a maximum activity at pH 9 at 45 degrees C and was stable at a broad pH range of 6-10. Lipase of P. expansum showed a preference for triacylglycerols, but no positional specificity. PMID- 8504154 TI - Saturated dicarboxylic acids as products of unsaturated fatty acid oxidation. AB - Upon chemical, radiation-induced or enzymatic oxidation, cis-polyunsaturated fatty acids, i.e., C18:2(n-6), C18:3(n-3), C20:2(n-6), C20:3(n-6), C20:3(n-3), C20:4(n-6), C20:5(n-3), C22:2(n-3), C22:4(n-6), C22:6(n-3), were found to generate saturated short and medium-chain length dicarboxylic acids, which can be regarded as a distinctive feature of the particular double bonds positions in the polyunsaturated fatty acid molecule. Two different dicarboxylic acids, which were unambiguously quantified by GC-MS, were produced from a single fatty acid: one deriving from the oxidative splitting at the level of the first double bond in the molecule, the other being two-carbon-atoms lower homologous. Formation of dicarboxylic acids occurred also from triacylglycerols and phospholipids containing cis-polyunsaturated fatty acids. In this case, following oxidation, the diacids remained covalently bound to the starting molecule and transesterification was necessary for identification. Being extremely stable and easily detectable compounds, dicarboxylic acids may be considered potential markers of oxidative attack to both free and esterified unsaturated fatty acids. PMID- 8504155 TI - Re-uptake of nascent low-density lipoproteins by HepG2 cells. AB - The kinetics and specificity of the interaction of nascent HepG2 LDL with the HepG2 LDL receptor were examined. 125I-Labeled HepG2 LDL and plasma LDL were bound by HepG2 cells in a specific and saturable manner at 4 degrees C. Competition studies with HepG2 LDL and plasma LDL indicated that both ligands bound to the same receptor. Scatchard analyses of the specific 4 degrees C binding data revealed a Kd of 75 nM for HepG2 LDL and a Kd of 30 nM for plasma LDL suggesting that HepG2 LDL bind less efficiently to the HepG2 LDL receptor than plasma LDL. Binding, internalization and degradation studies carried out at 37 degrees C indicated that HepG2 cells are capable of catabolizing their own nascent LDL; however, under normal experimental conditions re-uptake of nascent LDL is quantitatively insignificant. PMID- 8504156 TI - Effects of triiodothyronine administration on dietary [14C]triolein partitioning between deposition in adipose tissue and oxidation to [14C]CO2 in ad libitum-fed or food-restricted rats. AB - Refeeding a chow meal containing [1-14C]triolein to food-restricted rats results in increased accumulation of [14C]lipid in carcass and epididymal adipose tissue and lower oxidation to [14C]CO2 compared to ad libitum-fed rats (Biochem. J. 285, 773-778, 1992). In the present experiments the effects of treatment with triiodothyronine (T3) for three days on lipid accumulation in refed food restricted rats has been examined. T3 decreased accumulation of [14C]lipid in carcass and epididymal adipose tissue (32 and 77%, respectively) of food restricted rats on refeeding the chow-[1-14C]triolein meal. This decreased accumulation of [14C]lipid was accompanied by increased [14C]CO2 production (77%) and decreased heparin-elutable lipoprotein lipase activity in the epididymal fat pad (90%) and subcutaneous adipose tissue (80%). Accumulation of [14C]lipid in the latter did not decrease significantly. In contrast, T3 treatment of ad libitum-fed rats increased [14C]lipid deposition in carcass (44%) and in subcutaneous adipose tissue (240%) on refeeding, when compared to untreated ad libitum rats. Lipoprotein lipase activity in the two adipose tissue depots of the refed ad libitum+T3 rats, however, decreased. Thus, the effects of T3 on [14C]lipid deposition are adipose-tissue-depot-specific and depend on the previous dietary intake (over 14 days) of the rat. T3-treatment increased the lipoprotein lipase activity released from perfused hearts to a similar extent in both food-restricted and ad libitum-fed rats compared to the corresponding untreated groups. The rates of lipogenesis in-vivo in liver, epididymal and subcutaneous adipose tissue of food-restricted rats refed chow were not altered by T3. It is concluded that the increased deposition of dietary lipid in the food restricted rat can be partially reversed by treatment with T3, suggesting that the low-T3 state associated with this condition may be in part responsible. PMID- 8504157 TI - Phospholipase D activity of human amnion cells stimulated with phorbol ester and bradykinin. AB - We investigated the activity of phospholipase D (PLD) in human amnion cells labeled with [3H]oleate. The PLD activity was detected as signal-induced synthesis of phosphatidic acid (PA) and in the presence of ethanol, phosphatidylethanol (PEt). The PLD was shown to be activated by phorbol, 12 myristate, 13-acetate (PMA), calcium ionophore A23187, oxytocin, bombesin and bradykinin, but not by platelet-activating factor (PAF) and epidermal growth factor (EGF). The amniotic PLD thus appeared to be activated by a variety of agonists but with a certain specificity to stimulators. We examined the mode of the PLD activation using PMA (20 nM) and bradykinin (1 microM) as model stimulators. PMA and bradykinin elicited a rapid and sustained response with the peaks of PA-labeling attained at 5 and < 1 min after stimulation, respectively. In both cases, there was a concomitant rise of diacylglycerol (DG), and the PA accumulation was suppressed by ethanol at the expense of labeling of PEt. The PA synthesis caused by the two stimulators was similarly inhibited by staurosporine and by a chronic treatment with PMA (100 nM for 24 h), suggesting that the activation of PLD is linked to the action of protein kinase C. With the cells labeled with radioactive choline and ethanolamine, we found that the amniotic PLD hydrolyzed almost equally phosphatidylcholine and phosphatidylethanolamine. Although bradykinin and PMA stimulated cellular PLD to a comparable extent, prostaglandin (PG)E2 release was not stimulated by bradykinin in contrast to the marked effect by PMA. Further work is thus needed to clarify the significance of the novel PLD signaling pathway in the function of amnion cells. PMID- 8504158 TI - Rehydration induces rapid onset of lipid biosynthesis in desiccated Nostoc commune (Cyanobacteria). AB - Water, which contained [1,3-3H]glycerol, [35S]sodium sulfate, or [32P]sodium orthophosphate, was used to rehydrate air-dried cells of the desiccation-tolerant filamentous cyanobacterium Nostoc commune. The cells retained their capacities for the uptake and transport of all three compounds and, in response to rewetting, they mobilized the radiolabels into lipid precursors and initiated complex lipid biosynthesis. The onset of these events, measured in short-term, long-term and pulse-chase labeling experiments, was judged to be very rapid. The radiolabeled pool sizes of the major membrane species phosphatidylglycerol (PG) and sulfoquinovosyl diacylglycerol (SQDG) reached steady-state within several minutes, while those of the two abundant membrane glycolipids, mono- and di glycosyldiacylglycerol (MGDG, DGDG), achieved uniform labeling within 2 h. The pattern of sulfolipid synthesis was generally more complex than the other lipid species. Analysis of the maturation of SQDG through differential labeling provided the only example of a lag in lipid maturation during the early stages (minutes) of cell rehydration. In this instance, the lag appeared to be associated specifically with the incorporation of 35SO3- by the sulfoquinovose. During the initial 2 h of rewetting there was complete turnover of 3H-label in the pools of the principal lipid precursors 1,2-sn-diacylglycerol and 1,3 diacylglycerol. In contrast, the accumulation of label by the major lipid of the heterocyst cell-wall, a non-saponifiable glycolipid, became detectable only after 24 h of rewetting. The present data are discussed in relation to the basis for desiccation tolerance in N. Commune. PMID- 8504159 TI - Cholesterol 7 alpha hydroxylase promoter separated from cyclophilin pseudogene by Alu sequence. AB - The promoter for human cholesterol 7-alpha hydroxylase has been cloned and sequenced. In the regions previously described, our sequence agrees well with one report but not with another. At position -469, we find a widespread MaeII polymorphism. At -2636, there is an Alu sequence flanked by runs of adenines. Upstream of the Alu sequence, there is a cyclophilin pseudogene oriented in the opposite direction. PMID- 8504160 TI - Crystalline cylindrical structures of Na(+)-bound dimyristoylphosphatidylglycerol as revealed by microcalorimetry and electron microscopy. AB - Multilamellar vesicles of dimyristoylphosphatidylglycerol (DMPG) in an aqueous medium of 1 M NaCl at pH 7.0 converted to defined cylindrical structures of crystalline phase, on annealing of 5 degrees C of a gel phase temperature. The new crystalline phase transformed into the liquid crystal phase at a transition point (44.2 degrees C) nearly the same as that of the protonated DMPG, but with a transition enthalpy (19.2 kcal/mol) larger than that of the Ca(2+)-bound DMPG of much higher transition temperature. Electron microscopic observations revealed that a set of outer membranes (8-10 lamellae) separated from the MLV grows into helical structures and, finally, into the crystalline cylindrical structures with an increase in annealing time. PMID- 8504161 TI - The presence of GM1 in liposomes with entrapped doxorubicin does not prevent RES blockade. AB - The incorporation of ganglioside GM1 or phosphatidylethanolamine polyethyleneglycol conjugates into liposomes can result in extended circulation lifetimes in vivo. This has been attributed to an ability to avoid uptake by the reticuloendothelial system (RES), specifically the phagocytic cells of the liver and spleen. Here we examine whether a representative large unilamellar vesicle (LUV) formulation which contains GM1 (distearoylphosphatidylcholine/cholesterol/GM1, 45:45:10 mol/mol), actually does avoid the RES. It is shown that a pre-dose of LUVs which contain GM1 and entrapped doxorubicin blocks the accumulation of subsequently injected empty distearoylphosphatidylcholine/cholesterol liposomes in liver. It is therefore concluded that liposomes exhibiting extended circulation lifetimes can induce RES blockade and do not avoid uptake by liver phagocytes. PMID- 8504162 TI - Luciferase from the east European firefly Luciola mingrelica: cloning and nucleotide sequence of the cDNA, overexpression in Escherichia coli and purification of the enzyme. AB - We have cloned cDNA encoding luciferase in Luciola mingrelica, fireflies living near the Black Sea in southern Russia, and obtained high level expression of the cloned sequences in Escherichia coli. The nucleotide sequences of two isolated clones were determined; five single base differences were observed, but none resulted in a change in the encoded amino acid residue. The cDNA encoded a protein of 548 amino acid residues. The overall amino acid sequence identity with the luciferase from Photinus pyralis, the North American firefly, was 67%, while comparison of the L. mingrelica luciferase with L. cruciata and L. lateralis, both indigenous to Japan, showed about 80% of the residues were strictly conserved. A novel overexpression system which employs the regulatory genes of the luminous bacterium Vibrio fischeri allowed growth of cultures to high cell density and high luciferase content, facilitating purification of the enzyme. Luciferase was purified to homogeneity in good yield from lysates of recombinant E. coli by ammonium sulfate fractionation and chromatography on columns of DEAE Sephadex and Blue Sepharose. The physicochemical properties of the luciferases from the available recombinant sources are significantly different and should allow detailed investigations into the mechanism of the bioluminescence reaction and the physical basis of the differences in the color of light emitted from the various enzymes. PMID- 8504163 TI - Differential expression and stability of poly(ADP-ribose)polymerase mRNA in human cells. AB - The regulation of the expression of the poly(ADP-ribose)polymerase gene was studied in HeLa cells and in quiescent and mitogen-stimulated human lymphocytes by quantitating the mRNA molecules with a new technique based on the polymerase chain reaction. Using plasmid constructs containing defined sequences of the poly(ADP-ribose)polymerase cDNA as internal standards in a competitive PCR reaction, precise measurements of reverse transcribed mRNA copies per microgram of total RNA were obtained. The value found for asynchronously growing HeLa cells (8.6 x 10(5) copies) was very close to that observed for proliferating lymphocytes (8.7 x 10(5)) whereas a 20-fold lower value (0.4 x 10(5)) was obtained for quiescent lymphocytes. The determination of the stability of the mRNA of the enzyme in G0 and stimulated lymphocytes, and in HeLa cells was performed by devising a new PCR amplification system, using non-competitive conditions and plasmid target sequences as internal standards. The half-life of mRNA for poly(ADP-ribose)polymerase was approx. 1 h in G0 lymphocytes and 4-5 h in stimulated lymphocytes and in HeLa cells. This observed difference in stability of the transcripts can partially account for the observed difference in mRNA levels between G0 and stimulated human lymphocytes. PMID- 8504164 TI - Conserved cysteine residues of Oct-2 POU domain confer sensitivity to oxidation but are dispensable for sequence-specific DNA binding. AB - The POU family of proteins, including the Oct-2 transcription factor, is characterized by a highly conserved bipartite DNA binding domain containing a 'POU homeodomain', distantly related to homeodomains of other DNA binding proteins, and a 'POU specific' domain unique to this class of factors. Prompted by the finding that in vitro DNA binding by Oct-2 is reversibly inhibited by oxidation of the protein, we investigated the role of the cysteine residues in the POU domain. All POU homeodomains identified contain a cysteine in the helix 3 region presumed to contact DNA directly; many (including Oct-2) also contain a less-well conserved cysteine residue(s) in the POU specific domain. Replacement of these cysteines with serine residues rendered the DNA binding domain resistant to oxidation but did not appreciably change the binding to a canonical octamer sequence, suggesting that the conserved cysteine residues are not required for sequence-specific DNA contacts, but may be important for another function. PMID- 8504165 TI - Rat liver flavin-containing monooxygenase (FMO): cDNA cloning and expression in yeast. AB - A rat liver cDNA clone, RFMO1, coding for a flavin-containing monooxygenase (FMO) was isolated. This cDNA clone encoded a protein of 532 amino acids. The deduced amino acid sequence was 84, 82 and 82% identical to those of the pig, human (Form 1) and rabbit (Form 1) liver FMOs, while it was only 52, 50, 54, 56 and 54% identical to the human (Form II), human (Form 2) and rabbit liver FMOs (Form 2) and rabbit and guinea pig lung FMOs. RNA blot analysis showed that rat liver FMO was also expressed in lung and kidney and to a lesser extent in the heart and brain. An expression plasmid, pAMFMO, was constructed and the FMO protein expressed in yeast (AH22). This FMO protein catalyzed thiobenzamide S-oxidation, and NADPH oxidation associated with the S- or N-oxidation of thiourea, N,N dimethylaniline, trimethylamine, imipramine, chlorpromazine, N,N dimethylhydrazine, thioacetamide as substrates. The S-oxidation activities of thiobenzamide and thiourea were enhanced by n-octylamine, a known enhancer of FMO, and inhibited by alpha-naphthylthiourea, a known inhibitor of FMO. This is the first report in which FMO with catalytic activities was stably expressed. PMID- 8504166 TI - Expression and alternative splicing of fibronectin mRNA in human diploid endothelial cells during aging in vitro. AB - Different mRNAs for fibronectin arise from the variable processing of a single primary transcript. We used ribonuclease protection assay to investigate the changes occurring in fibronectin expression and the alternative splicing of mRNA precursor during aging in vitro of human diploid endothelial cells. Senescent endothelial cells release more protein and contain 4-5-fold more fibronectin mRNA than young cells. The pattern of alternative splicing of fibronectin mRNA, with the EDA and the CS1 segments largely included (35% and 77%, respectively) and the EDB segment undetectable, correlates well with previous studies at the protein level both in vitro and in vivo. No changes in the splicing pattern of fibronectin mRNA precursor were detected during endothelial cellular senescence. The increased expression of fibronectin in senescent cells may be a result of the activity of interleukin-1 alpha, which is overexpressed in senescent endothelial cells. It could be also important in vivo during aging and in atherosclerotic lesions. PMID- 8504167 TI - HL35e and HLA: primary structure of two very basic and cysteine-rich ribosomal proteins from Haloarcula marismortui. AB - Two small and very basic ribosomal proteins have been purified from the 50S ribosomal subunit of the archaebacterium Haloarcula marismortui by RP-HPLC. The complete primary structures of these two proteins, which we refer to as HL35e and HLA, have been determined by protein chemical methods. Both proteins are characterized by a high content of basic amino acids and the presence of two pairs of cysteines in each polypeptide chain, one of which resembles the C4-zinc finger motif. Comparison of the protein sequences with those of other ribosomal proteins revealed that HL35e shows significant sequence homology exclusively to eukaryotic ribosomal proteins, namely to yeast L35 and to L37 from rat. For HLA no homologous ribosomal protein so far known could be found. Obviously, HL35e and HLA have no counterparts in eubacterial ribosomes. PMID- 8504168 TI - Cloning, expression and in vitro characterisation of the M13 gene 5 protein. AB - The gene 5 protein encoded in the genome of bacteriophage M13 is a single stranded DNA binding protein essential for phage replication. We have cloned a fragment of the M13 genome containing gene 5, and investigated the effect of upstream elements on expression of the gene by means of Bal 31 deletion analysis. The gene was also expressed from the lac promoter of the phagemid vector pUC119, and the recombinant protein purified and characterised for DNA binding. The affinity of the recombinant protein for single-stranded DNA was shown to be essentially identical to that of wild type gene 5 protein. Wild type gene 5 protein has a glutamic acid residue at position 30 which, on the basis of the crystal structure, was believed to play a role in maintaining the tertiary structure of the protein through the formation of a salt bridge with arginine-80. We show that substitution of glutamic acid at position 30 by lysine does not impair DNA binding, suggesting that a salt bridge between glutamate-30 and arginine-80 is not essential for the structural integrity of the gene 5 protein as previously proposed. PMID- 8504169 TI - Inhibition of CpG methylation in linker DNA by H1 histone. AB - H1 exerts a specific in vitro inhibitory effect on enzymic DNA methylation. The experiments reported in this paper were undertaken in order to assess whether the lower methylation level found in internucleosomal DNA compared to core DNA is the in vivo consequence of the well-known localization of this histone in the linker region, as opposed to a possible deficiency of CpG dinucleotides in linker DNA. The methyl-accepting ability of H1-depleted oligonucleosomes from human placenta and of the corresponding core particles were assayed by addition of purified DNA methyltransferase, using S-adenosylmethionine as the methyl group donor. We have found that approx. 80% of newly-incorporated methyl groups are localized in linker DNA, which is indeed a good potential substrate for enzymic DNA methylation. Addition of quasi-physiological amounts of H1 to H1-depleted oligonucleosomes markedly reduced their methyl-accepting ability, while exerting a re-condensing effect on these particles, as revealed by the distortions of their circular dichroism spectra. PMID- 8504170 TI - The Dictyostelium myosin IE heavy chain gene encodes a truncated isoform that lacks sequences corresponding to the actin binding site in the tail. AB - We have isolated cDNA and genomic clones which together span the entire coding sequence for the 114.8 kDa heavy chain of Dictyostelium myosin IE (DMIE). The deduced primary sequence reveals a pattern characteristic of all myosins I, i.e., a myosin-like globular head domain fused to a tail domain that shows no similarity to the coiled-coil rod-like tail of type II myosins. The approx. 35 kDa tail domain of DMIE shows some sequence similarity to the membrane interaction region of other myosins I (tail-homology-region 1; TH-1), but lacks completely the sequences that correspond to the second actin binding site (the glycine-, proline- and alanine-rich TH-2 region and the src-like TH-3 region). Therefore, DMIE more closely resembles DMIA (Titus et al. (1989) Cell Regul 1, 55 63), which is also truncated, than DMIB and DMID, both of which possess all three tail homology regions. The similarity between the DMIE and DMIA isoforms extends to their pattern of expression, in which the steady state level of transcript for both genes is highest in vegetative cells and falls gradually after five to ten hours of starvation-induced development. Together, these results have important implications for interpreting and prioritizing gene targeting experiments designed to identify the functions of myosins I in vivo. PMID- 8504171 TI - The cDNA sequence of horse transferrin. AB - The cDNA sequence of horse transferrin was determined by sequencing clones isolated from a horse liver cDNA library and clones obtained by PCR. The 2305 bp horse transferrin cDNA sequence included part of the 5' untranslated region and extended to the poly(A) tail. It had 80% sequence identity with the human transferrin cDNA, and encoded a protein of 706 residues, including a signal sequence of 19 amino acids. The horse transferrin sequence had the duplicated structure and conserved iron binding and cysteine residues which are characteristic of the transferrin family. PMID- 8504172 TI - Identification of a nifW-like gene in Azospirillum brasilense. AB - A small ORF, 5' upstream of the fixABC operon in Azospirillum brasilense Sp7, has been identified. Sequence comparison shows significant homology to the Azotobacter vinelandii and Azorhizobium caulinodans nifW gene. PMID- 8504173 TI - Cloning and sequencing of a Xenopus homologue of the inducible orphan receptor NGFI-B. AB - A cDNA clone encoding the NGFI-B transcription factor, a growth factor inducible member of the steroid/thyroid receptor superfamily, has been isolated from a Xenopus neurula (stage 17 embryo) library. Sequencing of this clone reveals an open reading frame encoding a 577 amino acid protein. Comparisons with its counterparts in rat, mouse and human show that the Xenopus protein has a well conserved DNA binding domain whereas homology in the carboxy terminal region, which includes the putative ligand binding domain, is lower than that typically observed in members of the steroid/thyroid receptor superfamily. This relative lack of homology suggests that, in Xenopus, the as-yet uncharacterized ligand may have subtle distinctions from its mammalian counterparts. PMID- 8504174 TI - Solid-phase introduction and intracellular photoinduced reaction of a water soluble meso-tetracarboxyporphine conjugated to an antisense oligodeoxyribonucleotide. AB - Oligonucleotide conjugated with water-soluble meso-tetra(4-carboxyphenyl) porphine (TPPC4) has been prepared by a supporting synthesis and novel solid phase conjugation strategy. The conjugates could be used in dual fashion: i) on formation of iron complex, target DNA could be site-specifically cleaved on incubation with dithiothreitol; ii) on incubation of RR 1022 rat epithelial cell culture with non-metalized oligonucleotide TPPC4 conjugate, cytotoxic effect was detected after irradiation with laser light at 635 nm. PMID- 8504175 TI - Reversible covalent attachment of cholesterol to oligodeoxyribonucleotides for studies of the mechanisms of their penetration into eucaryotic cells. AB - A method in which a cholesterol moiety was covalently attached to oligonucleotides via a disulfide bond has been proposed as a means for studying the penetration of oligonucleotides into living cells. This bond may be cleaved by a mild treatment with thiol-containing reagents during some stages of the uptake process. Attachment of the cholesterol moiety resulted in a 30-50-fold increase in uptake of the oligonucleotide derivative by T24 human carcinoma cells. However, more than 80% of the oligonucleotide derivative remained on the external surface of the cellular membrane. Within the cytoplasm, the oligonucleotide derivatives were found in endosome-like vesicles which were observed during the first 6 h following treatment. Oligonucleotide moieties never cross the membrane, and endocytosis, with or without receptors, is the principal mechanisms for cellular uptake. Only about 15% of the oligonucleotides that penetrated the cells were found in the nuclear fraction. Treatment of the cells with dithiothreitol resulted in a release of most of the cell-associated oligonucleotide derivatives from the external surface of the membrane, but did not change the chemical state or intracellular distribution of the penetrated oligonucleotide derivatives. Mechanisms of the binding of cholesterol-modified oligonucleotides to cellular membranes, non-receptor mediated endocytosis and the role oligonucleotide transportation mechanisms play in determining the fate of penetrated oligonucleotides within the cell are discussed. PMID- 8504176 TI - Antisense effect of oligodeoxynucleotides complementary to the mini-exon sequence of the protozoan parasite Leishmania amazonensis. AB - We have targeted the mini-exon of Leishmania amazonensis, the sequence present at the 5' end of every mRNA of this protozoan parasite, with a complementary 12-mer, either unmodified (12 Le II) or linked to an acridine derivative (12 Le II Acr). Physical measurements performed either in solution or on nitrocellulose filters showed that the two oligomers exhibited the same affinity for both DNA and RNA target sequences. Furthermore, the two oligomers 12 Le II and 12 Le II Acr inhibited in vitro translation of L amazonensis mRNAs, in a wheat germ extract, to the same extent. Those results indicated that the intercalating agent did not stabilize the duplex formed by the antisense oligomer and its target sequence. PMID- 8504178 TI - Kinetic study of the addressed modification by hemin derivatives of oligonucleotides. AB - Kinetics of oligonucleotide pd(TGAATGGGAAGA) modification by a hemin derivative of the complementary oligonucleotide pd(TTCCCATT) in the presence of hydrogen peroxide was investigated. The treatment of experimental data permitted to evaluate the association and rate constants at 25 degrees C: Kx = (3.40 +/- 0.38) x 10(5) M-1 (association constant of the reagent with the target), kd = 152 +/- 6 M-1 min-1 (degradation constant of the hemin group of the reagent in a parallel reaction), ko = 51.0 +/- 1.7 M-1 min-1 (target modification constant in the reactive duplex). The modification of DNA is incomplete due to competition of the modification reaction with the degradation of the hemin group of the reagent in a parallel reaction. PMID- 8504177 TI - Inhibition of HIV proliferation in MT-4 cells by antisense oligonucleotide conjugated to lipophilic groups. AB - Anti-HIV activity of antisense oligonucleotide derivatives conjugated to lipophilic groups has been investigated. Aliphatic linear structures and cholesterol were coupled to the 5'-terminal phosphate of oligonucleotides via glycine or propylene diamine spacers. The oligonucleotides were targeted to a conserved sequence of the viral gene env, to a sequence in the negative sense viral RNA, to the 5'-terminus of the gene rev and to poly(A) sequences. The conjugation with lipophilic groups stimulated binding of oligonucleotides to cells and protected the oligonucleotides against cellular nucleases. The lipophilic derivatives of oligonucleotides containing an ester bond in the linker structure were cleaved by cellular esterases yielding oligonucleotides protected from 5'-nuclease degradation by the glycine residue. Antiviral activity of the derivatives exceeded that of the corresponding unmodified oligonucleotides. The virus suppression was sequence-specific and most pronounced in the case of the cholesteryl conjugated oligonucleotides. PMID- 8504179 TI - Effect of cytokine-specific antisense oligonucleotides on the immunoglobulin production by rat spleen cells in vitro. AB - We examined in this study the regulation of immunoglobulin (IgM, IgG, IgE) production by spleen cells from N brasiliensis infected rats following addition of antisense oligodeoxynucleotides (ODNs). The ODNs were selected near the AUG initiation codon of mRNA specific for interleukin 4 (IL-4) or interleukin 2 (IL 2). Results show that addition of antisense to IL-4 inhibited IgE production, while the production of IgG and IgM increased. The use of sense IL-4 sequence did not affect immunoglobulin production. In contrast, the use of antisense IL-2 ODN induced an enhancement of IgE as well as of IgM and IgG responses. Both the Ig secretion in culture supernatants and the number of Ig secreting cells, as detected by an Elispot assay, were influenced by the presence of antisense IL-4 ODNs. These results clearly show the involvement of IL-2 and IL-4 in the regulation of isotype selection during antibody synthesis and that IL-2 and IL-4 do operate differently on IgE production. They also argue that antisense strategy represents a useful tool for the antibody regulation. PMID- 8504180 TI - Inhibition of potato spindle tuber viroid (PSTVd) infection with DNA oligonucleotides. AB - The effects of DNA oligonucleotides complementary to potato spindle tuber viroid (PSTVd) on viroid infection were investigated. The oligonucleotides were used to form hybrids with PSTVd in the infection mixture. A 75% reduction of viroid infection was found when an oligonucleotide complementary to nucleotides 79-110 of PSTVd was hybridized with PSTVd at a molar ratio of approximately 5000:1, respectively. A total inhibition of PSTVd infection was observed using an oligonucleotide complementary to nucleotides 42-78 at the same molar excess of DNA over PSTVd, although a 200-fold molar excess was found to be sufficient for the complete blocking of infection by PSTVd. This oligonucleotide caused a significant reduction (about 83%) of viroid infection even if the hybridization was done at a low (30 degrees C) temperature. Shorter oligonucleotides containing 22 and 15 bases corresponding to position 42-62 and 63-78, respectively, exhibited a significant effect only at a high (80 degrees C) initial temperature of molecular hybridization. Heteroduplexes formed between PSTVd RNA and antisense DNA were found to be less stable in a crude nuclease extract from tomato leaves as compared with PSTVd RNA alone. RNase H was demonstrated to cleave the molecular hybrids in vitro. PMID- 8504181 TI - NMR studies on penicillins: hydrogen bonding, self-association and micellar solutions of cloxacillin Na-salt in D2O. AB - Self-association and formation of micellar solutions of cloxacillin sodium salt (CLO-Na) dissolved in heavy water have been investigated by NMR-spectroscopy. Concentration and temperature dependence of proton and carbon chemical shifts of cloxacillin-Na in D2O is presented and certain 1H and 13C NMR line assignments have been substantiated. PMID- 8504182 TI - Chiral separation and detection enhancement of propranolol using automated pre column derivatization. AB - In the liquid chromatographic analysis of pharmaceuticals, two challenges are often encountered: detectivity and chiral separations. Propranolol, a beta adrenergic blocker, is a pharmaceutical compound that faces both of these limitations. In this study, both limitations are overcome simultaneously using derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), a highly fluorescent and chiral reagent. The derivatization is automated using an autosampler with an AutoMix microrobotic feature, which greatly contributes to the efficiency and reproducibility of the method when manipulating microliter volumes of sample and reagents. The method yields excellent separation of the diasteriomers, has a detection limit of 1 picomol, good reproducibility and linearity in the 50-400 pmol range (on column). In addition, this method is simple, requires no elevated temperature, no chiral stationary or mobile phases and can be easily automated. PMID- 8504183 TI - Simple methods for the qualitative identification and quantitative determination of macrolide antibiotics. AB - Pyrolysis-gas chromatography is shown to be a rapid straightforward method for the qualitative differentiation of the macrolide antibiotics erythromycin, oleandomycin, troleandomycin, spiramycin and tylosin. Organic salts do not interfere and identification of erythromycin and troleandomycin in commercial products is viable. Spectrophotometric quantitation of these same five antibiotics after reaction with concentrated sulphuric acid is studied at about 470 nm. Reaction conditions such as acid concentration, time and temperature are provided. The sugar moieties of the antibiotics are proposed as the reactive sites. Detection limits are about 0.2-1.0 microg ml-1 [corrected] and analysis of pharmaceutical products should be possible. PMID- 8504185 TI - The effect of mobile phase modifiers on the simultaneous LC elution of a gadolinium complex and free ligand. AB - A liquid chromatographic method was developed for simultaneous separation of a gadolinium complex and corresponding ligand using a reversed-phase anion-exchange column. The effect of mobile phase pH, EDTA and chloride ion concentration, added to the mobile phase as counter-ions, on the elution of a metal complex and ligand were investigated. Decreasing the mobile phase pH from 9.4 to 7.4 decreased the retention time of the free ligand but had little effect on changing the retention time of the complex. Increasing the EDTA concentration of the mobile phase from 0 to 0.5 mM decreased the retention of the free ligand but had little effect on changing the retention time of the metal complex. Both the retention times of the metal complex and free ligand decreased as the chloride ion concentration was increased from 0 to 0.2 M. PMID- 8504184 TI - A stability-indicating assay and the preformulation characteristics of the radiosensitizer, 1,2,4-benzotriazin-3-amine 1,4-dioxide. AB - A stability-indicating LC assay was developed for the analysis of 1,2,4 benzotriazin-3-amine 1,4-dioxide and applied to the preformulation characterization of the drug. The dissociation constants of the drug were determined using UV-vis spectrophotometry. The LC method was used to determine the aqueous stability of the drug under a variety of accelerated conditions, its solubility in a variety of pharmaceutical solvents and its octan-1-ol-water partition coefficient. The preformulation data were used to develop three prototype aqueous formulations of the drug at a concentration of 0.5 mg ml-1 in 5% Dextrose Injection USP, phosphate buffer (pH 7.4) and phosphate buffered mannitol. The 3-month stability of those formulations at room temperature was demonstrated. PMID- 8504186 TI - Quantitative analysis of cefradine by liquid chromatography on poly(styrene divinylbenzene). AB - A method is described for isocratic analysis of cefradine by liquid chromatography on a poly(styrene-divinylbenzene) column (PLRP-S, 250 x 4.6 mm i.d.) at 50 degrees C. Cefradine is separated from its related substances using a mobile phase of acetonitrile-0.02 M sodium 1-octanesulphonate-0.2 M phosphoric acid-water (14.5:10:5:up to 100, v/v/v/v). The flow rate was 1.0 ml min-1 and UV detection was performed at 254 nm. The method was employed for the quantitative analysis of reference substances, bulk samples and pharmaceutical dosage forms. PMID- 8504187 TI - Determination of the beta-adrenergic blocker timolol in plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. AB - A method based on LC-MS-MS has been developed for the determination of timolol in plasma using the (CD3)3-labelled species as the internal standard. Timolol is isolated from plasma by a simple solid-phase extraction and converted to its oxazolidin-2-one prior to analysis on a 50 x 4.6 mm reversed-phase high performance liquid chromatography column packed with SynChropak, C18, 5 microns. The column eluate is passed by means of a heated nebulizer interface into a corona discharge atmospheric pressure chemical ionization source where the analyte and its internal standard are detected using multiple reaction monitoring (MRM). The very high specificity of this technique permits chromatographic run times of less than 2 min. The method has a lower quantifiable limit of 0.5 ng ml 1, with intra- and inter-day relative standard deviations less than 10%, and enables the determination of timolol in plasma after ocular administration to volunteers. PMID- 8504188 TI - Determination of cimetidine in pure form and in dosage forms using N bromosuccinimide. PMID- 8504189 TI - NMR of biofluids: detection of 2H-acetate and 2H-formate in urine as an indicator of microbiological contamination. PMID- 8504190 TI - Determination of phenylmercuric nitrate in pharmaceuticals by HPLC. PMID- 8504191 TI - Utility of column switching to analyse low dose dissolution samples for pharmaceutical formulations. PMID- 8504192 TI - Conformation of human calcitonin gene-related peptide (8-37) in aqueous solution as determined by circular dichroism spectroscopy. AB - Circular dichroism (CD) studies on CGRP(8-37) indicate that there is some latent alpha-helical structure in aqueous solution. However, the amount is quite small (approximately 10% at 5 degrees C), which is substantially less than for CGRP itself (approximately 15-20%). Upon addition of helix-promoting materials, such as trifluoroethanol and sodium dodecyl sulphate, the helix content increases dramatically. No evidence for helix stabilization upon the addition of zinc was observed. PMID- 8504193 TI - Quantitation of hydroperoxides in the aqueous solutions of non-ionic surfactants using polysorbate 80 as the model surfactant. AB - The application of coupled oxidation of NADPH to peroxide quantitation in non ionic surfactant solutions is demonstrated using polysorbate 80 as the model surfactant. The linearity, precision, accuracy, and sensitivity of the method are discussed. The method has the following advantages over the traditional iodimetric method: (1) it is not affected by the non-ionic surfactant present in the solution; (2) it is reactive to less reactive hydroperoxides; (3) it is not light sensitive; and (4) it is carried out at near physiological pH in aqueous solutions. The method was employed to monitor the peroxide concentration of polysorbate 80 solutions stored under three different conditions. The effects of light and heat on peroxide concentration are more pronounced in more dilute solutions (0.1 and 1%). The peroxide concentration determined in the freshly prepared polysorbate 80 solution can be converted to the peroxide number of the raw material, which is not available from the supplier of polysorbate 80. PMID- 8504194 TI - Cellular biology of bone resorption. AB - Past knowledge and the recent developments on the formation, activation and mode of action of osteoclasts, with particular reference to the regulation of each individual step, have been reviewed. The following conclusions of consensus have emerged. 1. The resorption of bone is the result of successive steps that can be regulated individually. 2. Osteoclast progenitors are formed in bone marrow. This is followed by their vascular dissemination and the generation of resting preosteoclasts and osteoclasts in bone. 3. The exact pathways of differentiation of the osteoclast progenators to mature osteoclasts are debatable, but there is clear evidence that stromal cells support osteoclast generation. 4. Osteoclasts are activated following contact with mineralized bone. This appears to be controlled by osteoblasts that expose mineral to osteoclasts and/or release a factor that activates these cells. 5. Activated osteoclasts dissolve the bone mineral and digest the organic matter of bone by the action of agents secreted in the segregated microcompartments underlying their ruffled borders. The mineral is solubilized by protons generated from CO2 by carbonic anhydrase and secreted by an ATP-driven vacuolar H(+)-K(+)-ATPase located at the ruffled border. The organic matrix of the bone is removed by acid proteinases, particularly cysteine proteinases that are secreted together with other lysosomal enzymes in the acid environment of the resorption zone. 6. Osteoclastic bone resorption is directly regulated by a polypeptide hormone, calcitonin (CT), and locally, by ionized calcium (Ca2+) generated as a result of osteoclastic bone resorption. 7. There is new evidence that osteoclast activity may also be influenced by the endothelial cells via generation of products including PG, NO and endothelin. PMID- 8504195 TI - Effects of protein kinase C activation on intracellular Ca2+ distribution in vascular smooth muscle cells of spontaneously hypertensive rats. AB - Protein kinase C is known to influence contraction in vascular smooth muscle cells by Ca(2+)-dependent and Ca(2+)-independent mechanisms. In the present study, the effect of protein kinase C activation by phorbol 12-myristate 13 acetate on resting cytosolic free Ca2+ and on cellular Ca2+ pools was assessed in cultured rat aortic muscle cells using fura 2. Cellular Ca2+ pools were evaluated with the selective inhibitor of the sarcoplasmic Ca2+ ATPase, thapsigargin. In normotensive vascular smooth muscle cells, protein kinase C activation caused a redistribution of Ca2+ from the thapsigargin-sensitive pool into the cytoplasm, whereas, in hypertensive cells, no significant effect of protein kinase C activity on cellular Ca2+ distribution was found. It is concluded that protein kinase C modulates the amount of Ca2+ stored in the thapsigargin-sensitive calcium stores. In hypertensive cells, the regulation of Ca2+ pools by protein kinase C is disturbed. PMID- 8504196 TI - Expression of two alternative splice forms of the insulin-like growth factor-I gene in human vascular endothelial cells. PMID- 8504197 TI - Mechanism of mastoparan-induced EDRF release from pulmonary artery endothelial cells. AB - Mastoparan is a wasp venom peptide that activates G-proteins, certain classes of which are involved in the release of endothelium-derived relaxing factor (EDRF). In the present study, we investigated whether this peptide might be a useful tool with which to elucidate the signal transduction pathways responsible for EDRF release from pulmonary artery endothelium. Mastoparan (10-50 micrograms/ml) elicited an increase in endothelial cell cytosolic free calcium concentration ([Ca2+]i) and EDRF release in a concentration-dependent manner. Both effects were dependent on Ca2+ influx, as they were inhibited by removal of extracellular Ca2+. In addition, when endothelial cells were suspended in Ca(2+)-free buffer, mastoparan inhibited ATP-induced increases in [Ca2+]i, presumably by depleting intracellular Ca2+ stores. More importantly, mastoparan also caused the release of fura-2 from dye-loaded endothelial cells, unlike ATP, which did not affect fura-2 loss. These data indicate that although mastoparan may act on G-proteins to elicit release of Ca2+ from intracellular stores, the primary mechanism of action responsible for mastoparan's ability to elicit EDRF release is an increase in cell membrane permeability followed by an influx of extracellular Ca2+. PMID- 8504198 TI - Mesenteric arcade arteries contribute substantially to vascular resistance in conscious rats. AB - This paper describes a new technique for determining the intravascular pressure at the base of mesenteric arcades (arterial diameter less than 200 microns) in conscious, unrestrained, resting rats, using this technique we found that under Brietal anaesthesia, shortly after implanting the catheters, the pressure in the base of the arcades (Pmes) was 86% of systemic pressure (Psys). After recovering from the anaesthetic, 6-8 h later, while Psys rose from average 79 to 114.5 mm Hg, Pmes/Psys fell to 69%. By contrast, when anaesthesia was induced, although Psys immediately fell by 44%, Pmes/Psys did not change. Acute pharmacological experiments in resting animals showed that the relative contribution of the arcade vessels to the peripheral resistance was variable. When serotonin was injected into the aorta, although Psys was unaffected, Pmes/Psys fell from 67 to 27%. Conversely, with noradrenaline, Psys rose by 30%, but Pmes/Psys remained unchanged. Angiotensin-II showed a third pattern, where Psys increased by 38%, but Pmes/Psys rose transiently to 86%. The data suggest that in the rat mesenteric bed, under conscious conditions, the arcade arteries can contribute substantially to the control of peripheral resistance. PMID- 8504199 TI - Angiotensin II stimulates increased protein synthesis, not increased DNA synthesis, in intact rat aortic segments, in vitro. AB - There is considerable controversy regarding whether angiotensin II (AngII) stimulates hypertrophy or hyperplasia of vascular smooth muscle cells (SMC). The purpose of the present study was to determine whether stretch of the vessel wall or AngII treatment increased protein or DNA synthesis in intact aortic rings in vitro and whether stretch of the vessel wall altered the growth responses to AngII. Rat aortic rings were mounted on steel supports in serum-free medium for 16 h and subjected to 0 or 1.5 g of preload (i.e. passive stretch). Fetal bovine serum (13%, FBS) or AngII [1 microM, in the presence or absence of angiotensin receptor antagonist, losartan (DuP753) 10 microM] was administered and isometric tension development was measured. 35S-methionine (3 microCi/ml) was added to the baths at 14-16 h for measurement of protein synthesis. Passive stretch did not increase protein synthesis as compared to vessels mounted under no-preload conditions. AngII and FBS elicited similar increases in isometric tension development, but tension development in FBS-treated rings was sustained 4 times longer than in rings treated with AngII. AngII and FBS increased protein synthesis by 35 and 121%, respectively, but there was no difference in the extent of contractile agonist-induced protein synthesis between rings subjected to 0 or 1.5 g of passive stretch. Losartan totally abolished AngII-induced tension development and protein synthesis. AngII and FBS did not stimulate increased DNA synthesis in aortic rings, as measured by 3H-thymidine incorporation. These results suggest that AngII stimulates hypertrophy rather than hyperplasia of fully contractile SMC in an intact vessel. PMID- 8504200 TI - Heterogeneous distribution of [3H]alpha,beta-methylene ATP binding sites in blood vessels. AB - A radioligand binding assay and autoradiographic localisation of P2X purinoceptors were carried out in several different blood vessels from rat, guinea-pig and rabbit by using [3H]alpha,beta-methylene ATP ([3H]alpha,beta MeATP) as the radioligand. The radioligand binding assay on rabbit ear artery showed that the binding process was saturable, and a high density of P2X purinoceptors was observed. Autoradiographic localisation showed that the specific [3H]alpha,beta-MeATP binding sites were only associated with the smooth muscle of the blood vessels. Semi-quantitation of the autoradiographs revealed significant differences in the densities of P2X-purinoceptors amongst the vessels studied. Generally the medium- and small-sized arteries had higher densities of P2X-purinoceptor than the elastic and large muscular arteries. In some large muscular arteries, such as the rabbit carotid, renal, hepatic and mesenteric, the outer region of vessel had a higher density of receptors than the inner region. The veins in this study were sparsely labelled, except portal veins where the longitudinal and circular layers of muscles were found to have different densities of P2X-purinoceptors. The results from this study provide direct evidence for the existence of P2X-purinoceptors in blood vessels; furthermore, the distribution of the P2X-purinoceptors is consistent with known pharmacological responses elicited by ATP in these vessels. PMID- 8504201 TI - Comparison of the interferon-gamma-mediated regulation of tumor-associated antigens expressed by human gastric carcinoma cells. AB - The regulation by interferon-gamma (IFN-gamma) of the expression of seven distinct human tumor-associated antigens [M 110,000, carcinoembryonic antigen (CEA), nonspecific crossreacting antigen (NCA), CA19-9, 17-1A, TAG-72, and D612] was studied in eight human gastric cancer cell lines. Six of the seven tumor antigens have been well-characterized and reported to be expressed by human gastric carcinomas. The M(r) 110,000 antigen has been recently identified in six of the eight human gastric cancer cell lines and may represent a potentially novel gastric tumor antigen. IFN-gamma administration substantially increased the expression of the M(r) 110,000 antigen in six gastric tumor cell types, and, furthermore, induced its expression de novo in another gastric tumor cell line (GaCa). Constitutive CEA and NCA expression was detected on the surface of five of the eight gastric carcinoma cell lines. IFN-gamma treatment induced only a modest increase in the level of expression of those related antigens, but those changes were accompanied by increases in the level of the respective mRNA transcripts. Four other human tumor-associated antigens, TAG-72, CA19-9, D612, and 17-1A, were found either to be not constitutively expressed and/or not regulated by IFN-gamma. The results indicate the selective nature by which IFN gamma regulates the M(r) 110,000 antigen and, to a lesser extent, the antigens of the CEA gene family. PMID- 8504202 TI - Teratogenic hydrazines: a review. AB - The review summarizes the results of 30 hydrazines, which were studied in humans and in six animal species for teratogenic activities. Of these, 23 chemicals were found to induce physical defects in the developing embryos of animals. Six hydrazines failed to induce teratogenic abnormalities in animals under the experimental conditions. Three hydrazine analogues, some of which were given in combination with other drugs to pregnant women, gave ambiguous results concerning teratogenic effects. Some of these investigations were aimed at revealing the teratogenic mode of action of hydrazines. The mechanistic aspect focused on the dose requirements of chemicals and the time period in the development of the fetus susceptible to malformation and chemoprevention. Of interest is the base compound hydrazine, which was found to be teratogenic in five animal species. In general, the hydrazines were found to be powerful teratogens, which coincided in most cases with their known carcinogenic activities. PMID- 8504203 TI - Effects of luteinizing hormone-releasing hormone analogue on DNA synthesis in rat prostate and uterus. AB - Buserelin, a potent LH-RH agonist, has been used for the treatment of hormonal disorders such as precocious puberty, endometriosis, cystic mastitis and prostatic carcinoma. Prolonged treatment with buserelin has been known to induce a refractory phase of pituitary desensitization. In the present study, we found that two-week treatment with buserelin strongly suppressed the activities of thymidylate synthetase and thymidine kinase, and markedly reduced the appearance of BrdU-immunoreactive (S-phase) cells in both prostate glands and uteri in male and female adult rats, respectively. PMID- 8504204 TI - Comparison of the cardiotoxic effects of liposomal doxorubicin (TLC D-99) versus free doxorubicin in beagle dogs. AB - The cardiotoxic potential of liposome encapsulated doxorubicin (TLC D-99) prepared by a remote-loading technique was compared with that of free doxorubicin (1.5mg/kg administered every 3 weeks for 8 cycles) in beagle dogs. Both agents were equally myelosuppressive, and all dogs completed both treatments. There were no deaths during the study. Experimental animals were killed between 157 and 164 days after the start of the trial. All of the dogs (n = 6) that received free doxorubicin had either moderate (1 animal) or severe (5 animals) vacuolization of myocardial tissue. None of the dogs treated with liposomal doxorubicin had lesions suggestive of cardiomyopathy. Administration of free doxorubicin was associated with transient anorexia, reduced weight gain, alopecia, and gastrointestinal toxicity. Such adverse reactions were either much less severe or absent in animals that received liposomal doxorubicin. The results of this study demonstrate that TLC D-99 significantly decreases both the myocardial toxicity and other adverse reactions of this potent antineoplastic drug. TLC D-99 is now in Phase II clinical trials. PMID- 8504205 TI - In vivo distribution of radio-labeled tumor infiltrating lymphocytes in cancer patients. AB - Tumor-infiltrating lymphocytes have proven effective in murine tumor models and preliminary clinical trials. To evaluate the efficacy of these lymphocytes in treatment attempts were made to study the in vivo migration and distribution of these lymphocytes. Tumor-infiltrating lymphocytes isolated from five patients with malignant metastatic breast cancer or melanoma cultured and expanded in vitro with low-dose of recombinant interleukin-2 were labeled with 111Indium oxine and infused to the patients. A large view gamma camera was used to evaluate the distribution and localization of the infused TIL. Localization of 111In labeled TIL in the lungs was seen within two hours after infusion and high levels of radioactivity were observed at 24 hours in lungs, liver and spleen. The activity in the lungs diminished after 72 hours. No specific localization of 111In-labeled TIL was observed in the metastatic sites. PMID- 8504206 TI - Effects of castration and thyroidectomy on expression of lectin-binding sugar moieties and endolectins in mouse submandibular glands. A glycohistochemical study. AB - The aims of this study were to assess histochemically by means of biotinylated lectins and neoglycoproteins the effects of castration and thyroidectomy on the expression of carbohydrate moieties and endogenous sugar-binding proteins (endolectins), respectively, in submandibular glands of mice. Characteristic binding patterns depending upon the type of lectin were observed primarily in the granular convoluted tubules. For the first time carbohydrate-binding sites were also localized in this glandular tissue. Moreover, the endocrine status was found to affect the histochemical expression of sugar moieties of glycoconjugates as well as endolectins, thus modifying both sides of presumed protein-carbohydrate interactions. Further work is needed to identify these molecules and to understand better their endogenous roles. PMID- 8504207 TI - Platelet function in the dorsal skin fold chamber of the rat. AB - The majority of the preparations described for studying platelet functions in vivo require the administration of anesthetic agents and surgery. Some anesthetic which are frequently used in microvascular research (such as ketamine hydrochloride and pentobarbital) are reported to exert an effect on platelet properties themselves. Using a modified chamber preparation situated in the rat's dorsal skin fold, it is possible to study platelet function in the same rat with or without anesthesia. Thrombus formation is induced in arterioles and venules by argon-laser irradiation with a local capacity of 25mW and an exposure time of 1/30 s. Platelet function was studied for ten successive days in the same group of rats to examine the model's aptitude for long-term investigations. There was no significant alteration in platelet response during the experimental period. To evaluate the potential antithrombotic effects of the anesthetics, the animals were studied before and after the application of ketaminehydrochloride (130 mg/kg b.w., pentobarbital (25 mg/kg b.w.), or urethane (1,25 g/kg i.m.). The first two drugs caused significant increase in the number of laser injuries in arterioles and venules, although the effect of pentobarbital was weaker especially in venules. The influence of thrombus formation while using these anesthetics could influence the testing of antithrombotic drugs. Urethane had no effect on laser induced thrombus formation. Furthermore, special attention was paid to spontaneous and laser-induced vasomotion with respect to thrombus formation. PMID- 8504208 TI - Influences of high dietary fat and/or indomethacin on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in rats. AB - We investigated the effects of a high-fat diet and indomethacin on tumorigenesis, tumor proliferation and cell kinetics of 7,12-Dimethylbenz(a)anthracene (DMBA)- induced mammary carcinomas in Sprague-Dawley (SD) rats. Both the high-fat diet and indomethacin significantly stimulated tumor proliferation and cell kinetics, whereas tumorigenesis was significantly stimulated by the high-fat diet but it was significantly inhibited by indomethacin. Moreover, switching the animals from the high-fat diet with or without indomethacin to the low-fat diet suppressed tumor proliferation and cell kinetics. It can therefore be concluded that either a high-fat diet or indomethacin stimulates tumor proliferation in DMBA--induced mammary carcinoma in SD rats. PMID- 8504209 TI - Species differences in carcinogenesis. AB - There are differences in response of different species to many carcinogens. Different organs respond to particular carcinogens, there are differences in potency (including resistance of some species), and there are varying effects of other parameters. Although animal studies identify carcinogens, it is impossible to predict accurately the potency or the target organ in humans of any carcinogen. Inter-species differences in response to carcinogens can be due to differences in metabolism and activation. However, even in the case of directly acting carcinogens, such as alkylnitrosoureas, quantitative differences in alkylation of DNA are insufficient to explain the differences in response of particular organs. Yet unknown reactions or interactions of carcinogens must be key factors in inter-species differences. PMID- 8504210 TI - In vivo characterization of immunogenicity of a mitoxantrone-resistant murine P388 leukemia. AB - The Mitoxantrone-resistant murine leukemia P388/Mitox, expressing the multidrug resistant phenotype, has a higher immunogenicity than the parent sensitive P388. This could be shown in vivo by immunization with lethally-irradiated tumor cells. If the P388/Mitox was used for immunization before subsequent challenge with viable tumor cells of the same line, this resulted in a partial rejection of tumors and production of a substantial number of tumor-free survivors. For an effective immunization at least two primings s.c., i.v. or i.p. with at least 10(6) irradiated cells were necessary. This protected the recipient mice from a challenge of up to 10(8) viable cells over a period of at least 75 days. Treatment of BDF1 mice with the T-cell suppressor Cyclosporin A prevents immunization. In nude mice no immunization effect could be obtained. It was possible to transfer immunity adoptively with spleen cells from mice, which were treated with irradiated tumor cells of the P388/Mitox line. Treatment of tumor bearing mice with IL-2 resulted in a prolongation of survival both when it was administered prophylactically before transplantation of P388/Mitox and at an advanced stage (day 7-11). Also the alkyl-phosphocholine hexadecylphosphocholine was significantly effective in the resistant but not in the parent P388 leukemia. The data presented demonstrate that by development of a multidrug-resistance, concomitantly a xenogenization must have taken place which leads to a recognition of cells by immune mechanisms. In our model, T-lymphocytes and NK-/LAK-cells probably play a role in the immunologically conditioned rejection of tumor cells of the P388/Mitox leukemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504211 TI - Further studies on the carcinogenic-free interval following exposure in experimental esophageal tumorigenesis. AB - 247 C57B1 male mice were killed after Diethylnitrosamine (DEN) treatment at various time intervals ranging from one day to nine months. The number of esophageal tumors was divided by the length of the resected esophagus (i.e. Tumor Index = TI). Animals treated for up to 2 months had a TI of 0.1. Since the histological examination of the esophagi in those animals revealed only normal histology, the conclusion drawn was that the TI of 0.1 was a methodological error in assessing esophageal tumors by transillumination. Three months' treatment with DEN resulted in a 9-fold increased TI and 6 months' treatment in a 69-fold increased TI. Other groups of animals treated with DEN for the same period of time were allowed to survive 7, 9 or 12 months without further treatment. Animals treated with DEN for 1 day but followed without further treatment for 7 months demonstrated a 3.5-fold increased TI. For animals treated with DEN for only 14 days, (TI 0.1) and followed for 7 months with a carcinogenic-free diet, a 7-fold TI was observed. For the group of animals treated for 3 months (TI 0.9) but allowed to survive to complete 7 months on a carcinogen-free diet, a 5-fold higher TI was recorded. DEN animals treated for 6 months (TI 6.9) but allowed to survive 3 additional months had a TI of 9.6. A similar TI, namely 9.7, was found when the carcinogen-free interval was prolonged for 6 more months. These results suggest that clones of esophageal cells are "programmed" for tumor growth at an early stage of DEN treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504213 TI - Rejection of the colon in multi visceral organ transplantation in pigs. AB - We studied the rejection of the colon by performing multiple visceral organ transplantation in non-inbred Large White Duroc pigs. The rejection of the colon was graded as follows: Grade I, infiltration by lymphocytes and/or plasma cells in the mucosa on days 7-8 (the day of transplantation = day 0). Grade II, more intense infiltration in the mucosa and/or submucosa and scattered epithelial sloughing and cryptitis in the mucosa on days 10-14. Grade III, transmural infiltration and complete mucosal destruction on days 18-21. PMID- 8504212 TI - Preclinical toxicology study of liposome encapsulated doxorubicin (TLC D-99): comparison with doxorubicin and empty liposomes in mice and dogs. AB - A preclinical toxicology study of intravenously administered liposome encapsulated doxorubicin (TLC D-99), free doxorubicin and empty liposomes was carried out in mice and dogs by single and multiple (daily for 5 days) dose schedules. Single dose intravenous injection studies in mice showed the encapsulated form of doxorubicin to be less toxic (LD50 of 32 mg/kg) than free doxorubicin (LD50 of 17 mg/kg). Toxicity in dogs was evaluated by serial serum chemistry, hematology and EKG analysis, urinalysis, clinical observations, necropsy and histopathologic examination. Empty liposomes injected intravenously into dogs were without significant toxicity. The maximally tolerated dose of free doxorubicin in beagles was 1.5 mg/kg; deaths were seen after a 50% escalation to 2.25 mg/kg. The maximally tolerated dose of liposome encapsulated doxorubicin was higher (2.25 mg/kg); deaths were seen after a 50% escalation to 3.37 mg/kg. A toxicity unique to the encapsulated agent was pyexia (as high as 105.6 degrees F) within twenty four hr of single dosage. This was seen in approximately half of the test animals, was not dose-related, and was not observed in animals that received empty liposomes. The organ specific toxicities seen with TLC D-99 were qualitatively similar to those of free doxorubicin, but less severe. PMID- 8504214 TI - Persistent changes in protein synthesis by vagina of ovariectomized mice exposed neonatally to diethylstilbestrol. AB - Neonatal treatment of female mice with a synthetic estrogen, diethylstilbestrol (DES), results in adenosis, ovary-independent epithelial proliferation and cornification, and downgrowths in the vagina. Protein synthesis was examined in the vagina of 45-day-old, ovariectomized C57BL/Tw mice which had been given 5 daily injections of 2 micrograms DES or the oil vehicle alone from the day of birth, and in those of age-matched, ovariectomized mice given 3 daily injections of 0.1 microgram DES from 42 days of age. [35S]Methionine-labeled proteins of the vagina were analyzed by two-dimensional polyacrylamide gel electrophoresis. Major changes were observed in 11 proteins of the vagina in both neonatally and postnatally DES-exposed groups. Six of the 11 proteins were increased in expression, but one of the remaining proteins was decreased. In the group of neonatally DES-exposed mice alone, expressions of 4 proteins (MW. 128, 90, 46 and 44 kDa) were markedly increased. These results indicate that neonatal exposure of mice to DES induced ovary-independent, persistent alteration in the protein synthesis of the vagina. PMID- 8504215 TI - Early events in the assembly of MHC class I antigens. AB - The MHC class I heavy chain and beta 2-microglobulin are cell surface proteins, and are synthesized on membrane bound ribosomes. They are co-translationally inserted into the endoplasmic reticulum (ER) membrane and assemble with antigenic peptides in the lumen of this compartment. These peptides are believed to be generated in the cytosol, and must be protected from degradation prior to translocation across the ER membrane. Putative peptide transporters (TAP1 and 2) belonging to the ABC transporter family of proteins, have been suggested to function in this process, and have been shown to be essential for MHC class I antigen assembly. The finding that peptides were translocated across the ER membrane in microsomes prepared from cells lacking the TAP genes has challenged this view. In this review we discuss the different events leading to correct assembly of MHC class I antigens. We suggest the TAP molecules to be part of a complex, which function to select peptides, protect them from degradation, and facilitate their translocation by targeting them to the ER membrane. PMID- 8504216 TI - Peptide antigen presentation by non-classical MHC class I molecules. AB - The mouse major histocompatibility complex contains more than 40 class I genes in addition to those encoding the classical class I molecules. Many of these encode functional class I heavy chains that are expressed and displayed on the cell surface in association with beta 2-microglobulin. Several laboratories, using genetic, biochemical, and molecular analysis, RMA-S mutant cells, and synthetic peptides, have recently shown that mouse non-classical or class Ib molecules present peptide antigens to T lymphocytes with alpha beta or gamma delta receptors. The class Ib genes, with their limited polymorphism, may have evolved to serve specialized presentation functions. PMID- 8504218 TI - Structural analysis of MHC class I molecules with bound peptide antigens. AB - Three-dimensional structures of human and murine MHC class I molecules in complex with peptide antigens have begun to elucidate the mechanism of peptide binding. The MHC molecule has a highly conserved structure in which important variation occurs only in the residues lining the central polymorphic portion of the peptide binding cleft. Peptides bind in extended conformations deep within the cleft and have highly specific and conserved interactions at their amino and carboxyl termini and divergent interactions in the middle. Peptides longer than the canonical length for a given allele appear to bulge in the middle but maintain their interactions at their ends. One or more anchor residues are used by the peptide to establish tight and enduring presentation to T cells. Peptide associated conformational differences in the MHC molecule itself may contribute to the T cell recognition process. PMID- 8504217 TI - Natural killer cells and the MHC class I pathway of peptide presentation. AB - Natural killer (NK) cells are TcR-Ig- lymphocytes that can mediate resistance to tumor growth, virus infections and bone marrow transplants. The receptors and specificity of NK cells are not clear, although it has been suggested that cytolytic triggering may be facilitated by lack of host matched MHC expression in the target or the graft. This article reviews and analyzes the role of the MHC class I pathway of peptide presentation in regulation of NK cells. This subject is introduced by brief overviews on NK cells, the 'missing self hypothesis' and studies establishing that MHC class I molecules of the target and the host can influence NK reactivity against certain normal and malignant cells. The main focus is then set on recent studies indicating that this influence occurs through interactions involving the antigen binding groove or its bound peptides. This includes discussion of modulation of NK sensitivity by peptides, beta 2 microglobulin, allelic differences or point mutations in MHC class I heavy chains, virus infection and peptide loading deficiency. While it is clear that alterations affecting the groove and its contents can change NK sensitivity, the evidence should be interpreted with caution, as the structural integrity of the whole class I molecule is dependent on the conformation and the stability of the antigen binding groove. Two models for recognition, 'target interference' and 'effector inhibition', are discussed. Each of these (mutually non-exclusive) models can accommodate a role for the groove and its peptide. PMID- 8504219 TI - The interaction of antigenic peptides with the H-2Kd MHC class I molecule. AB - An important event in the recognition of antigen by T cells is the selective interaction of peptides with major histocompatibility complex (MHC) molecules. We have defined several critical structural features that promote the efficient interaction of antigenic peptides with the MHC class I molecule, H-2Kd. For four unrelated antigens, we found that optimal synthetic peptides were short, only 9 or 10 amino acids long. These and other H-2Kd-restricted peptides were found to share a distinct 2-residue binding motif. Two regions in the H-2Kd antigen binding site that might accommodate the motif residues were identified by analysis of Ala-substituted H-2Kd molecules. A molecular model showing the possible interaction of one antigenic peptide with the H-2Kd molecule is presented. PMID- 8504220 TI - The Japan Society of Human Genetics Award Lecture. Molecular analysis of xeroderma pigmentosum group A gene. PMID- 8504221 TI - Interdependence of lumbar disc and subdiscal bone properties: a report of the normal and degenerated spine. AB - A nondestructive mechanical testing technique was used to assess midsagittal plane variations in the mechanical properties of human lumbar vertebral bone adjacent to the intervertebral discs of normal and degenerated spines. Bone mechanical properties were compared with midsagittal plane measurements of intervertebral disc (IVD) physical-chemical properties. In the normal spine a heterogeneous midsagittal plane distribution of subdiscal bone stiffness, IVD hydration and fixed charge density was found. Segments with degenerated discs exhibited a lower amount of midsagittal variation in subdiscal bone and IVD properties. A positive linear correlation between subdiscal bone stiffness and IVD fixed charge density was also found, suggesting that an interdependence of IVD and bone properties exists. These results support previous findings and are hypothesized to be an adaptive response to changes in the stress environment in the IVD. PMID- 8504222 TI - Body composition, endurance, strength, cross-sectional area, and density of MM erector spinae in men with and without low back pain. AB - Thirty-six 45-55-year-old men with healthy low backs were studied with respect to body composition, isokinetic and isometric trunk strength, trunk muscle endurance, and cross-sectional area and radiological density of mm erector spinae. Results were compared to those of men in the same age group with intermittent low back pain (LBP) (n = 91) and with chronic LBP (n = 21). The back healthy group was significantly stronger and had longer trunk muscle endurance times than men with chronic LBP. Men with intermittent LBP had strength and endurance values in between the back healthy and chronic groups. There were no significant differences between any of the groups with respect to body composition and cross-sectional area of mm erector spinae. Radiological density for mm erector spinae was significantly decreased in the chronic LBP group compared to the back healthy and intermittent LBP groups. The deconditioning syndrome and its relationship to intermittent and chronic LBP is discussed. PMID- 8504223 TI - Postmortem angiographic findings for arteries supplying the lumbar spine: their relationship to low-back symptoms. AB - We evaluated 56 postmortem lumbar aortograms to study differences between subjects with and without low-back pain in the lumbar and middle sacral arteries. Twenty-two of 25 (88%) cases with back pain history had one or more missing arteries, 20 (80%) of them had narrow arteries, and 18 (72%) had developed collaterals. The corresponding figures for 22 age-matched controls were 13 (59%), 12 (55%), and 12 (55%), and for nine young (i.e., age < or = 30 years) controls two (22%), two (22%), and two (22%). The cases had on average 2.04 entirely missing and 1.32 narrow (< or = 50% in diameter) arteries, compared with the age matched controls who had 0.82 missing (p < 0.001 for difference from cases) and 0.59 narrow arteries (p < 0.01). We conclude that insufficient arterial blood flow may be an underlying factor for low-back symptoms. Atheromatous lesions in the abdominal aorta or congenital hypoplasia of the arteries may explain the angiographic findings. PMID- 8504224 TI - Strength reductions from trabecular destruction within thoracic vertebrae. AB - An in vitro model of metastatic lesions in thoracic vertebrae was used to determine if the reduction in vertebral cross-sectional area could be used to predict the associated strength reduction. Defects, entirely within the trabecular bone, were created in alternating vertebrae of unembalmed human thoracic spines. The adjacent vertebrae were tested intact and served as controls. Defect size was determined as the cross-sectional area of the defect divided by the nominal cross-sectional area of the vertebral body midplane. Vertebrae were tested to failure using combined axial-flexion loads. For each spine, a linear regression was determined between the cross sectional area of the superior endplate and the load at failure for the intact vertebrae. The intact strength of bodies with defects was estimated from this regression. The normalized strength of thoracic vertebrae with trabecular defects was linearly related to the reduction in cross-sectional area (normalized failure load = 1.0 Ad/Ai, r2 = 0.51; Ad = cross-sectional area of defect; and Ai = intact cross sectional area at midplane). The data suggest that the strength reduction due to lytic defects within the centrum of thoracic vertebrae is proportional to the cross-sectional area of bone resorbed. PMID- 8504225 TI - Fat content of lumbar extensor muscles and low back disability: a radiographic and clinical comparison. AB - The fat content of the lumbar back extensor muscles was assessed from computed tomograms and correlated to self-reported disability in 39 consecutive chronic low back pain patients. The assessment for the quality of fat was done separately for the three lowest lumbar intervertebral levels. The Oswestry index was used to evaluate the low back disability. Analysis showed positive relationship between the fat content of the lumbar paraspinal muscles at lumbosacral level and self reported disability in men. The relationship was weaker in women, and at higher lumbar levels it was not found in either sex. PMID- 8504226 TI - Influence of pedicle fixation on postoperative pain. AB - From October 1988 through November 1990, 29 lumbar and lumbosacral spine fusion patients, 11 instrumented and 18 noninstrumented, were observed. Seventeen were men and 12 were women, with a mean age of 42.6 years (range, 22-83). The narcotic equivalent (NE) in milligrams/kilogram/day of medication used was analyzed. Age, sex, height, and weight were compared to the type, dose, mode, and duration of medication administration. Morphine was the reference point narcotic at 1.0:1.0. Levels fused, use of instrumentation, and prior surgery were related to NE. No significant differences in age, total body weight, height, levels fused, or hospital stay were established. There were 89.6% of patients over the ideal body weight by a mean 17.47 kg or 38.3 lb. The mean population NE was 3.76 mg/kg/day. Prior surgery patients tended to request narcotics intramuscularly for a longer period, while older patients tended to receive less medication. Patient obesity was related to lower NE. This study could not demonstrate a decrease in postoperative pain as it relates to the amount of narcotic medication received with the use of pedicle instrumentation. PMID- 8504227 TI - Effects of spinal cord ischemia on evoked potential recovery and postischemic regional spinal cord blood flow. AB - The effects of spinal cord ischemia on spinal cord blood flow (SCBF) and somatosensory (SSEP) and motor (MEP) evoked potentials were investigated in a rabbit model of reversible spinal cord ischemia. Spinal cord ischemia was produced by balloon occlusion of the infrarenal aorta for 30, 60, and 90 min. SCBF, SSEPs, and MEPs were measured before, during, and 1 h after aortic occlusion. Aortic occlusion produced absolute ischemia of the caudal cord followed by hyperemia upon reperfusion. SSEP's and MEP's were obliterated during ischemia but demonstrated gradual albeit incomplete recovery following reperfusion with amplitude recovery inversely proportional to the duration of ischemia. Later peaks were more severely affected by a given period of ischemia than were early waves. In general, SSEP's were more resistant to ischemia than were MEP's although the differences were not significant. PMID- 8504228 TI - Posterior element strength six months postinjury in the canine cervical spine. AB - In vivo and in vitro biomechanical studies from this research group revealed that acute differences in the range of motion of C4-C5 canine cervical spine injuries decreased over a 24-week healing period to approach control values. It could be inferred that the repair tissue replacing the injured posterior elements functionally returned the spine to normal. This study investigated the biomechanical properties of the healed tissue and the isolated adjacent posterior elements at each intervertebral level of these same specimens. Twenty-two animals underwent one of four procedures at the C4-C5 level: (a) sham procedure, (b) transection of the supra- and interspinous ligament, (c) laminectomy, or (d) laminectomy plus bilateral facetectomy of the inferior articular facets. Twenty animals survived the entire testing protocol. Twenty-four weeks after injury, destructive testing was performed on the isolated posterior elements in tension loading. The maximum load, elongation at maximum load, stiffness, and energy absorbed to the maximum load were measured. The posterior elements injured by all of the procedures behaved similarly across all experimental groups after 24 weeks of healing. A trend for decreased stiffness in the more extensive surgery groups was seen, but no statistically significant differences were found. This paralleled the results of prior in vivo and in vitro range-of-motion testing. PMID- 8504229 TI - Transverse ligament failure: a biomechanical study. AB - We investigated the biomechanical properties of the transverse ligament by simulating an anteroposterior shear injury mechanism. The ligament was tested in isolation. All secondary restraints and any interference from articular mass geometry were eliminated. In all, 13 specimens were tested. Eleven failed within the substance of the ligament, and two failed by bone avulsion. The mean load to failure was 692 N (range, 220-1590 N). The displacement to failure was 6.7 mm (2 14 mm). The measured values of load to failure agree with previous reports; however, the displacement to failure exhibited a broader range than expected. PMID- 8504230 TI - Critical analysis of strut grafts in anterior spinal fusions. AB - Fifty patients undergoing anterior spinal decompression with partial or complete corpectomy and fusion with strut grafting were reviewed. The etiology of the spinal lesions included pathologic fracture (9 patients), trauma (22 patients), congenital/developmental lesions (6 patients), failed fusion (6 patients), and degenerative lesions (7 patients). Vertebral body reconstruction of the cervical, thoracic, or lumbar spine used iliac crest (20 cases), rib (12 cases), and fibular autografts (9 cases). Additionally, in 10 cases fibular allografts were used. There were four deaths, all secondary to systemic disease. Of the remaining 46 patients, 2 required revisions and all subsequently progressed to a solid anterior arthrodesis with an average follow-up of 30.4 months (range 12-62 months). Posterior spinal fusion was staged in 38 patients. Twenty of 29 patients with neurologic lesions improved after corpectomy. Eleven cases treated for a progressive, painful kyphosis averaged correction of 11.4 degrees (26%), which was maintained on long-term follow-up. Complications were primarily pulmonary and/or genitourinary. Others included a pseudarthrosis, an early fractured strut, and a late allograft infection. On the basis of this review, it appears that spinal arthrodesis with anterior decompression and strut grafting is an effective method of treating anterior compressive syndromes of the spine and painful progressive kyphoses. PMID- 8504231 TI - Cervical injuries under flexion and compression loading. AB - Cervical spine segmental tests were performed to determine the specific patterns of initial cervical injury in response to loading just beyond the point of structural failure. Well-defined combinations of flexion rotation and compression translation were applied to segments with varying degrees of disc and facet degeneration. Twelve cervical spine specimens (from human cadavers ages 52-91 years), each consisting of three vertebrae (two motion segments) from the middle (C2-C5) or lower (C5-T1) regions, were subjected to pure flexion rotation (seven specimens) or to combined flexion rotation and axial compression translation (five specimens). Specimens were sectioned and dissected to determine the patterns of structural failure. Pure flexion, and combined flexion and compression produced similar patterns of injuries. The disc was the most commonly injured structure, with annular injuries noted in 8 of the 12 specimens, and with anterior herniation of the nucleus occurring in two specimens. Wedge fractures and posterior ligament injuries were noted in both specimen groups and with both modes of loading. We conclude that similar patterns of initial anterior bony compressive failure and posterior ligamentous failure can occur with both flexion and with combined flexion-compression, without axial or lateral rotation, at low rates of loading. Anterior cervical disc herniations were produced in both middle and lower cervical segments. PMID- 8504232 TI - Synovial cyst of the cervical spine. AB - Synovial cyst herniations, typically observed in the lumbar region in conjunction with degenerative changes of the facet joints, only rarely present as space occupying lesions in the cervical spine. The case of a 47-year-old white man with a C7-T1 synovial cyst impinging on the spinal cord and right C8 nerve root is presented. PMID- 8504233 TI - Outcome of two multimodal back treatment programs with and without intensive physical training. AB - We compared the results of two multimodal back treatment programs (program A: n = 134; program B: n = 175) using pain, functional capacity, sickness absence, subjective state of health, depression, and work status as outcome variables. Whereas in program A exercise was guided by pain, in program B a "no pain, no gain" rationale was used as a basis for intensive physical training. Neither of the programs included direct attempts to influence the patient's environment (i.e., to find employment or to modify working conditions). In both programs, a clear decrease in pain and an increase in functional capacity was found from the pretreatment phase to the 12-month follow-up. These changes were, however, stronger in program B. Days of absence decreased significantly in group B, but the change was not significantly different from that in group A. On the whole, the more intensive training showed somewhat better results, even though the difference was not substantial. In contrast to some earlier results, there was no statistically significant increase in the proportion of those employed after treatment in either group. The results indicate that intensive physical exercise does not, as such, solve the problem of back disability in a country that has a highly developed social security system. More active interventions in work and work-life are needed. PMID- 8504234 TI - Effect of immobilization and configuration on lumbar adjacent-segment biomechanics. AB - The motion and facet load changes at the adjacent segment after lumbosacral immobilization (with different angles) were quantified in vitro using canine spines. Changes were examined under flexion, extension, and lateral bending. An increase (extension: 62%; flexion: 85%; left bend: 30%; right bend 26%) in motion at the adjacent segment was found for all motions after immobilization. Adjacent segment facet load remained constant under any load state or immobilized configuration. For all configurations, the facet contact site impinged in extension, remained unchanged in left bending, and moved superiorly in right bending. This study has shown that after immobilization the facet contact patterns at the adjacent segment changed, load was unchanged, and segmental motion increased when the lumbar spine reproduced the same range of motion. The configuration of the immobilized segments had no effect on these changes. PMID- 8504235 TI - Excel: a new cell separator in its very first clinical application. AB - BACKGROUND: The evolution of technology has been one of the most interesting features that has accompanied thrombocytapheresis throughout the years. In this presentation we report on the preliminary results obtained with Excel, a third generation cell separator that is presently in its early experimental phase. MATERIAL AND METHODS: So far only 15 thrombocytapheresis procedures, 2 of which of the single-needle type, were carried out on 15 healthy donors processing 4 liters of blood (2.8 liters in single needle). RESULTS AND CONCLUSIONS: The results were satisfactory since the average platelet yield was 4.7 x 10(11). The leukocyte contamination was 0.8 x 10(6) and the RBC contamination 0.4 x 10(7). The platelet efficiency per minute was 6.5 x 10(9), and the run time average 72 min. As to the quality of the product the very first results of platelet aggregation, relative to pre-apheresis, were 78% in response to ADP 6 microM; 106 and 102% in response to collagen 4.5 micrograms/ml and ristocetin 1.5 mg/ml, respectively. Essentially no platelet aggregates were found in the platelet products (Wu-Hoak ratio: 0.91). PMID- 8504236 TI - [Storage of thrombocyte concentrates: quality control by in vitro bleeding test]. AB - BACKGROUND: The increasing demand for single-donor platelet concentrates necessitates the storage of these blood products prior to transfusion. Quality control of these platelets, however, is still a problem. Most of the available techniques are time-consuming and require sophisticated equipment and specifically trained personnel. The present paper describes a new method for quality control of stored platelet concentrates. MATERIALS AND METHODS: Single donor platelet concentrates were stored for 7 days; daily aliquots were taken and the in vitro bleeding time (Thrombostat 4000) and platelet aggregation (aggregometer) were determined. RESULTS: The in vitro bleeding test can be handled simply and fast. The results are comparable with those of platelet aggregation tests. CONCLUSION: The in vitro bleeding test provides a good alternative to the conventional methods commonly used for quality control of platelet concentrates. PMID- 8504237 TI - Reduction of plasma cold agglutinin titers by means of plasmapheresis to prepare a patient for coronary bypass surgery. AB - A 53-year-old man with abnormally elevated cold agglutinins was treated successfully by plasma exchange so that he was able to sustain coronary artery surgery and extracorporeal circulation. Two plasma exchanges, consisting in the exchange of one plasma volume with a 5% albumin solution each, were performed in our intensive care unit with careful monitoring of vital parameters. The plasma exchanges resulted in a reduction of the titer of the cold agglutinins and of the thermal amplitude as well. With the exception of postoperative bleeding requiring re-intervention, the patient was successfully operated and could be dismissed on the 16th postoperative day in good condition. PMID- 8504238 TI - Sporadic occurrence of Diego A antigens and antibodies in Berlin. AB - BACKGROUND: The antigen Dia is common among Mongols (5-12%), but rare in Caucasians (< 1%). OBJECTIVE: The accidental discovery of Diego A (Dia) antibodies in a South American tourist and in an elderly German patient prompted us to investigate the frequency of Dia antigens in the German population. DESIGN: 1,352 German random blood donors, all living in Berlin or in the areas around, were tested for the presence of the Dia antigen on their red blood cells. All donors were Caucasians. RESULTS: Dia was found in 12 individuals (0.89%). CONCLUSIONS: We think that Dia is a low-frequency antigen in the European population. The admixture of Mongol genes following wars or migration is only of low or no importance. PMID- 8504239 TI - [Enteral nutrition of critically ill patients]. AB - OBJECTIVE: The purpose of this article is to review the facilities of early enteral nutrition in critically ill patients. DATA SOURCES: Review articles as well as original papers are the main sources for this contribution. SELECTION CRITERIA: Pathophysiologic conditions of intestinal substrate assimilation during hypermetabolism are described. The resulting consequences for enteral alimentation are discussed. Practical aspects such as classification and different indications of formulas, performance of enteral nutrition as well as management of tube feeding complications are further subjects of this review. RESULTS: Paying attention to tolerance, enteral nutrition can be started early in the postoperative or posttraumatic course. Jejunal substrate application, however, reveals to be a major issue for successful management. CONCLUSION: Clinical performance as well as efficiency of enteral nutrition seem to be essentially dependent on the intestinal blood flow. New methods for estimating intestinal blood flow, such as tonometry, will have to be evaluated especially in critically ill patients to improve the indications for enteral nutrition. PMID- 8504240 TI - [The non-energetic importance of enteral nutrition of critically ill patients]. AB - OBJECTIVE: The aim of this review is to describe recently discussed nonenergetic effects of enteral nutrition. DATA SOURCES: Results of current animal and clinical studies are summarized and the place of enteral nutritional regimen in critically ill patients is discussed. SELECTION CRITERIA: The possible protective effect of early enteral nutrition in critically ill patients concerning stress ulcus prophylaxis, infections, and the pathogenesis of multiple organ failure is gaining particular attention in this review. RESULTS: The reduction of intestinal bacterial translocation and the decline of catabolism during enteral substrate application seems to be proven by animal experiments. CONCLUSION: The relevance of early enteral nutrition in critically ill patients, however, needs to be investigated in further clinical studies. PMID- 8504241 TI - [Perioperative steroid substitution in patients with adrenal cortex diseases]. AB - OBJECTIVE: To provide clinically feasible recommendations for diagnosis and replacement therapy with glucocorticoids in patients with adrenocortical disease and primary, secondary or iatrogenic adrenocortical failure. SOURCES: Personal clinical experiences and major clinical reviews pertinent to the problem. RESULTS: The internationally recommended therapeutic regimens are often controversial. Therefore, emphasis is put on detailed and reliable therapeutic schemes which consider the increased glucocorticoid requirement of patients with adrenocortical failure in perioperative or stressful conditions. A sufficient steroid cover is essential to prevent an acute adrenal crisis. It has to be taken into account that adrenocortical dysfunction frequently goes unrecognized in the emergency condition of critical illness if the possibility of its presence is not borne in mind. Moreover, special attention has to be paid, in particular, to the inadvertent corticosteroid withdrawal and its sequelae. CONCLUSION: The perioperative management of patients with diseases of the adrenal cortex is a continuing challenge to the interdisciplinary cooperation of surgeon, neurosurgeon, gynecologist, anesthesiologist and internist. PMID- 8504242 TI - [175 years ago: reawakening of blood transfusion in Europe]. PMID- 8504243 TI - [Risk of infection transmission by blood components]. AB - OBJECTIVE: Assessment of the present risk of blood-borne infection associated with homologous blood transfusion in Central Europe with particular emphasis on HIV and HCV infections. DATA SOURCES: The relevant literature in the English and German language and the authors' data. STUDY SELECTION: No special study has been carried out for the present paper. RESULTS: The recognition of the risk for transmitting HIV by transfusion has led to a bundle of measures which have improved the safety of blood supply in Germany. A stricter donor selection as well as screening for HIV 1 and HIV 2 have reduced the risk to transmit HIV to the order of 1 per 1 million units transfused. The transmission of hepatitis B is estimated to be in the order of 1:50,000. The anti-HCV testing, introduced in 1990, has markedly reduced the transmission of HCV to less than 1:5,000 per unit as judged from our own data. A further reduction is expected by an improved HCV screening in the near future. Fatal disease from bacterial contamination is rare, with an estimated risk of one in a million units. Syphilis transmitted by transfusion is virtually not occurring anymore. However, increased efforts should continue to enhance the safety of blood, bearing in mind that a zero risk is not achievable for effective therapies. The estimation of risks is a dynamic, time dependent value which has to be estimated for a geographically defined population for a given time period. CONCLUSIONS: The risk of transfusion-associated infection has been markedly reduced in recent years. Albeit there is a small but definitive risk, which is often overestimated. The risks have to be defined to estimate the risk/benefit ratio of the homologous as well as the autologous transfusion for the individual patient. PMID- 8504244 TI - Single-needle thrombo-cytapheresis with the Fresenius AS 104. AB - BACKGROUND: The Fresenius AS 104 cell separator has recently met some popularity in European apheresis units for the quality of the platelets obtained with the totally automated double-needle procedure. MATERIALS AND METHODS: Taking advantage of the machine's flexibility we have developed a new automated procedure for single-needle thrombocytapheresis (SNP). So far 61 SNP were carried out. From donors having a platelet precount of 2.74 x 10(5) an average of 3.8 x 10(11) cells were collected by processing 2.5 liters of blood in a run time of 83 min. RESULTS AND CONCLUSIONS: The leukocyte and erythrocyte contaminations were 2.7 x 10(7) and 3.5 x 10(7), respectively. Only 2 products did contain less than 3.5 x 10(11) platelets, and 7 procedures were complicated by minor signs of hypocalcemia. With minor modifications this SNP is presently offered on a routine basis to our platelet donors. PMID- 8504245 TI - Signal transduction in Bacillus subtilis sporulation. AB - The initiation of sporulation in Bacillus subtilis is regulated by a signal transduction system leading to activation (by phosphorylation) of the Spo0A transcription factor. Activated Spo0A controls the expression of genes encoding different RNA polymerase sigma factors, whose synthesis and activities are related to morphological events and intercompartmental communication between the developing forespore and the mother cell. PMID- 8504246 TI - RNA polymerase II transcription cycles. AB - RNA polymerase II interacts with transcription factors to initiate the synthesis of mRNA. These interactions are cyclic, involving multiple RNA polymerase subunits and general transcription factors. Phosphorylation of the RNA polymerase II carboxyl-terminal domain may regulate these interactions. PMID- 8504247 TI - Effects of DNA methylation on DNA-binding proteins and gene expression. AB - DNA methyltransferase is needed for normal development, perhaps because DNA methylation plays a part in the control of gene activity. It is clear that the methylation of promoters often leads to repression of transcription. Studies of the mechanism suggest that repression may either result from the direct effects of methylation on transcription factors, or may be indirectly caused by repressor proteins that bind to methylated DNA. Current evidence suggests that both mechanisms can be involved. PMID- 8504248 TI - Regulation of the beta-globin locus. AB - Transcription of the human beta-globin gene cluster depends upon upstream regulatory sequences, which are collectively termed the locus control region. Recent studies have provided new insights into how the individual genes of the cluster are regulated through development. The crux of transcriptional activation is how the locus control region communicates with the gene-proximal regulatory elements. PMID- 8504249 TI - Trans-acting factors involved in adipogenic differentiation. AB - The differentiation of preadipocytes into adipocytes in culture is accompanied by the coordinate transcriptional activation of adipose-specific genes. Recent studies have identified cis-acting elements that are involved in activating (or derepressing) the transcription of many of these genes during differentiation. The identification of key trans-acting nuclear factors that interact with certain of these elements makes it possible to formulate models for the regulatory network governing the adipogenic differentiation program. PMID- 8504251 TI - Transcription regulatory proteins in higher plants. AB - Novel structures and interactions for plant transcription factors have recently been reported. Factors that lack DNA-binding activity, exhibit putative triple helix DNA-binding motifs, or possess two DNA-binding domains are among the interesting results. Advances in our understanding of protein-protein interactions between plant transcription factors are facilitating the design of new experimental strategies to further define their roles in regulatory pathways. PMID- 8504250 TI - Regulation of the HNF-1 homeodomain proteins by DCoH. AB - The pattern of expression of homeodomain proteins often exceeds their apparent domain of activity. Tissue-specific proteins that modulate the in vivo activity of homeodomain proteins have been proposed to account for this functional restriction. The first identified example of such an accessory protein is DCoH, which confers transcriptional activity to the hepatocyte nuclear factor 1 and provides a model of how other accessory factors might modulate the function of homeodomain proteins. PMID- 8504252 TI - Lessons from lethal albino mice. AB - Results from the analysis of mice homozygous for lethal albino deletions suggested the existence of a locus involved in the regulation of gene expression in the liver. The surprising finding that the locus encodes an enzyme active in tyrosine metabolism forces us to re-evaluate the lethal albino phenotype and advises caution in the interpretation of seemingly simple phenotypes. PMID- 8504253 TI - Interactions of coiled coils in transcription factors: where is the specificity? AB - Amphipathic alpha-helices create the dimerization interface in the bZIP and bHLH classes of DNA-binding proteins. These amphipathic helices have been shown to enter into a wide variety of specific dimerization interactions, and this large array of possible combinatorial interactions may provide for fine control of biological function. In bHLH-ZIP proteins, the addition of a leucine-zipper region immediately carboxyl-terminal to the helix-loop-helix region provides for an additional level of both dimerization specificity and control, again through the interaction of amphipathic alpha-helices. Interhelical electrostatic interactions have been implicated in regulating dimerization specificity. PMID- 8504254 TI - Regulating the HO endonuclease in yeast. AB - The pedigree of mating-type switching in yeast is determined by the transcription pattern of the HO endonuclease gene, which is expressed during late G1 in mother cells but not at all in daughter cells. The late-G1 specificity of HO transcription depends on a heteromeric factor, SBF, which is composed of the Swi4 and Swi6 proteins. Mother-cell specificity involves a second site-specific DNA binding factor, Swi5, which is synthesized in the G2 and M phases and only enters the nucleus at the end of mitosis. Swi5 enters mother and daughter nuclei in equal amounts and most is then rapidly degraded. It has been suggested that in mothers but not in daughters some Swi5 protein escapes degradation and persists until SBF is activated in late G1. This subset of Swi5 molecules may constitute a mother cell's memory. PMID- 8504255 TI - Gene regulation: translational initiation by internal ribosome binding. AB - During the past year, several examples of cellular mRNAs have been described in which translational initiation occurs by internal ribosome binding, a mechanism hitherto thought to be restricted to picornaviral RNAs. New insights into the molecular mechanism of internal ribosome entry have been provided by the structural and functional analyses of both the internal ribosome entry sites and the protein factors that stimulate translation mediated by these elements. PMID- 8504257 TI - Gene expression and differentiation. PMID- 8504256 TI - Circadian-clock regulation of gene expression. AB - During the past year, our understanding of the cellular and molecular processes involved in the generation and control of circadian rhythms has advanced significantly. Progress has been made at the level of the circadian pacemaker mechanism itself, the input pathways that regulate the pacemaker, and the mechanisms by which the pacemaker regulates its various outputs. A common theme underlying all three of these processes is the involvement of transcriptional and translational control. This review is an updated and extended version of a review first published in Current Opinion in Neurobiology 1991, 1:556-561. PMID- 8504258 TI - [Seroprevalence of human immunodeficiency virus infection (HIV) in Mali on 3,496 sera]. AB - Our main objective has been geared toward the appreciation of the importance of the infection by human immunodeficiency virus in Mali. Our study was based on 3,496 sera deducted from March 1987 to January 1989. All positive sera at ELISA have been confirmed by Western Blot. The total seroprevalence of the study is 8.41%. This fact has been noticed higher in prostitutes, young men, more in women than in men in widows and divorced couples, in traders, in travellers of high endemic countries. The seropositivity is proportional to the number of sexual partners. The heterosexual way of transmission has been dominant. There has been no relationship between seropositivity and transfusion, antecedent of surgery, sexually transmitted diseases, of sexual intercourse type. The HIV2 has been more frequent than HIV1. Taking into account the importance of this infection, precautionary measures must be taken to avoid an evolution toward a catastrophic situation. PMID- 8504259 TI - [Clinical and biological aspects of a collective alimentary toxi- infection by group A streptococcus in a military unit stationed in Djibouti]. AB - An outbreak of streptococcal pharyngitis due to a group A beta-hemolytic streptococcus has occurred in a French Army unit based in Djibouti during the month of september 1991. Out of 304 sick soldiers, 73% were seen by a physician in the initial 48 hours of the outbreak. All the patients showed a sore throat, associated with myalgia and rachialgia (85%), headache (26%) and digestive signs (24%). They were given a systematic antibiotic therapy by a penicillin or a macrolide, so no post-streptococcal complication was observed. From 23 throat swabs, 10 Streptococcus pyogenes strains were recovered with identical chimiotype, antibiotype and serotype (T:11, M non typable). Five serological assays were performed on 33 paired (early and 15 days later) samples of serum: ASLO (latex agglutination and microtitration), ASH, ASD and ASK. ASLO microtitration with ASD appear to be the most profitable association. The cost of such an outbreak is very heavy. More, the operational capacity of this unit was seriously compromised as long as 6 days. Measures to be applied are those used for the prevention of foodborne diseases, including medical surveillance of the cooking staff and strict observance of cool conservation of cooked meals and foods. PMID- 8504260 TI - [Aedes albopictus in Europe: a real threat]. PMID- 8504261 TI - [Ephemeride and history of the Society]. PMID- 8504262 TI - [Antibiotic sensitivity of Salmonella strains isolated in a pediatric population in Dakar. Research of beta-lactamase and plasmids]. AB - 114 strains of Salmonella were isolated from many samples in the Pediatric Hospital (Hopital d'Enfants Albert Royer) of Dakar between January 1985 and December 1991. The sensibility to antibiotics were tested, and we studied the production of beta-lactamase and the presence of plasmids in the resistant strains. 27 serovars of Salmonella were identified and Salmonella typhi predominates with 45%. Only 28% of the strains were susceptible to all of the antibiotics, and 17% were found multiresistant; 8% of the strains produce beta lactamase and plasmids were found in 6 multiresistant strains. PMID- 8504263 TI - [In vivo resistance of Plasmodium falciparum to chloroquine in Anjouan (Comoros)]. AB - An in vivo study of P. falciparum sensitivity to chloroquine was conducted at Anjouan island (Republique federale islamique des Comores) from December 1990 to March 1991. The 27 patients included in the study were given chloroquine at a dose regimen of 25 mg/kg over 3 days and were followed up 7 days. Six patients (22.2%) still harboured parasites up to day 7, thus showing a RII/RIII level of resistance. This is likely related to an increased chloroquine consumption by the inhabitants of this island since 1987. PMID- 8504264 TI - [Current role of doxycycline in the chemoprophylaxis of Plasmodium falciparum malaria]. AB - In countries where chemoresistance of Plasmodium falciparum is high (group III), mefloquine must be advocated for malaria prophylaxis for a stay less than 3 months. If it is more and particularly in Indo-china peninsular countries (Thailand, Birmania, Kamputchea, Laos, Vietnam) and in Amazonia, advocated chemoprophylaxis is doxycycline 100 mg per day. Authors remind action mechanism, contraindication and side effects of this drug. Others publications underline the good tolerance of doxycycline now used by 1,400 french soldiers staying for 6 months with United Nations Organisation in Kamputchea. An evaluation of tolerance and efficiency of this chemoprophylaxis is now in progress. PMID- 8504265 TI - [Malaria in the village of Yaounde (Cameroon). 3. Parasitological study in 2 central districts]. AB - A parasitological study of malaria was carried out in two central districts of Yaounde (Cameroon) for one year. The Essos district was built near marshy shallows. The Obili district was comparable to Essos but there were many poorly maintained fish breeding pounds. Surveys were carried out quarterly in each district with a sample of 22 and 16 families at Essos and Obili respectively. The whole members of the families were examined. The study showed that the plasmodic index cumulated for the two districts was 25.4 +/- 2.7% (n = 960). The gametocytic index was 1.7 +/- 0.8% and the parasitic density was 310 parasites/microliters of blood. A significative difference in the plasmodic index was observed between the two districts: 28.7 +/- 3.6% (n = 592) in Essos and 20.1 +/- 4.1% (n = 368) in Obili (p < 0.02). The plasmodic index was higher in the 6 to 15 age group (37.5%) but the higher parasitic density was observed in the 0 to 5 age group (1,100 parasites/microliters of blood). Seasonal variations were noticed with the higher indexes in small dry season and the lower indexes in the big dry season. PMID- 8504266 TI - [Epidemiology of cysticercosis in Madagascar]. AB - By examining the sera from 1,408 healthy individuals in all six provinces of Madagascar with ELISA methods, we were able to demonstrate a very high prevalence for cysticercosis: 18%. The serologic markers for cysticercosis among 1,132 patients with neurologic symptoms was even higher: 36%. Furthermore, of 241 patients with neurocysticercosis, 82% of the serums recognized, in Western Blot test, the 14-20 Kd "evolutivity proteins". Cysticercosis is thus highly implicated in the neurologic syndromes found in Madagascar. Only adequate prophylaxis will permit a reduction in the incidence of this disease. PMID- 8504267 TI - [The culicidian fauna and its nuisance in Kinshasha (Zaire)]. AB - A public health study to inventory bloodsucking mosquitoes was conducted in Kinshasa and its regions. 20 culicidian species were represented by 7 Anopheles, 6 Culex, 5 Aedes and 2 Mansonia. In general, the number of bites/man/night (b/m/n) was in average 141.5 of Cx. quinquefasciatus, 60.1 of Cx. antennatus, 21.1 of M. africana, 16.3 of An. gambiae and 7.7 of M. uniformis. The nuisance is different from region to other. Culex quinquefasciatus is the most abundant and aggressive species in the urban area with an average of 400 b/m/n. In certain suburban zones, Culex antennatus is predominant, with aggression on the order of 176.5 b/m/n. The Anopheles gambiae complex is predominant in the semi-rural zone at the periphery of the city with 26.05 b/m/n. Other mosquitoes are equally implicated in their aggression and nuisance to man, in particular, Mansonia africana, Mansonia uniformis and Aedes aegypti. A geographical distribution map has been established for the preponderant species in Kinshasa. PMID- 8504268 TI - [Cutaneous signs of dengue. Apropos of 3 cases]. AB - We report three cases of dengue with cutaneous signs that were observed in three women returning from Asia (and that were confirmed by serology). The exanthem has common characteristics: progressive appearance beginning on thewer limbs, macula type elementary lesion associated with purpura, evolution in one single upward spread, confluent lesions with intervals of healthy skin, palmoplantar affection, disappearance of the eruption in an average of ten days, association with conjunctivitis in three cases, pharyngitis in two, epistaxis in two and haematuria in one. The lesions spread to the trunk in one patient only and another patient had pruritus. None of the patients showed signs of a state of shock. According to WHO and, despite the existence of haemorrhages and of a purpura, the three cases reported here cannot be considered as being dengue haemorrhagic fever due to the absence of hemoconcentration. The two types of cutaneous signs observed during the fever are described and their physiopathology is discussed. PMID- 8504269 TI - Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs. AB - Rejection of T-depleted BMTs is predominantly mediated by alloreactive host T cells. A low but significant number of radiochemoresistant clonable T cells can be detected following a conventional cytoreductive protocol given prior to T depleted BMT. Elimination of these cells increases the engraftment rate. We found no clonable T cells at the end of the conditioning regimen in 100 ml of peripheral blood from 47 patients who received an HLA-identical T-depleted BMT. None rejected the graft and none displayed mixed chimerism. In addition, although no clonable T cells were detected in nine patients who received a mismatched BMT, two rejected their graft. However, in three mismatched patients, who for clinical reasons received a modified pre-BMT schedule, the presence of host clonable T cells was associated with immunological rejection. These findings suggest that the detection of clonable T cells should prove a valuable indicator for optimising immunosuppression prior to T-depleted BMT. PMID- 8504270 TI - High frequencies of cytotoxic T cell precursors against minor histocompatibility antigens after HLA-identical BMT: absence of correlation with GVHD. AB - Limiting dilution analysis was used to quantify the frequency of cytotoxic T cell precursors (CTLp) against minor histocompatibility (H) antigens induced by HLA identical BMT. The development of CTLp was monitored serially in ten patients developing either acute (n = 3), acute and chronic (n = 4) or no (n = 3) GVHD. In blood samples of patients taken shortly after BMT (< 100 days) a high frequency of anti-recipient CTLp was found (mean 1/3433). With time, this value decreased to become undetectable (< 1/500,000) beyond 400 days. This occurred also in patients still suffering from chronic GVHD. In contrast, autologous BMT did not induce any measurable recipient-reactive CTLp at any time point after BMT. In the early phase of reconstitution after BMT the frequency of CTLp against allo HLA antigens was measured in the same patients. The absence of a consistent increase of allo-specific CTLp indicates that the kinetics of CTLp against host minor H antigens does not merely reflect an overall changed cytolytic potential shortly after BMT. These results indicate that: (1) HLA-identical BMT induces high frequencies of minor H antigen-specific CTLps detectable in the blood during the early phase of reconstitution, and (2) the frequency of recipient-reactive CTL measured in the peripheral blood is not an adequate parameter for GVHD. These data therefore challenge the clinical value of in vitro measurement of recipient reactive CTLs in the peripheral blood after HLA-identical sibling BMT. PMID- 8504271 TI - Prostaglandin E2 for prophylaxis of oral mucositis following BMT. AB - Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients. PMID- 8504272 TI - Mucormycosis in the BMT population. AB - Mucormycosis is known to cause rhinocerebral and pulmonary disease in patients with diabetes, leukemia, and lymphoma. However, the characteristics and outcome of these infections have not been well described in the BMT population. In a 17 year consecutive series of BMT patients, 13 of 1500 patients (0.9%) developed mucormycosis. Ten of the transplants were allogeneic and three autologous. Six infections occurred within 90 days of transplant, and six occurred at or within several days of autopsy. Seven patients were neutropenic and another patient had just engrafted at diagnosis of infection. Sites of infection were lung-brain (n = 4), sinonasal region (n = 3), lung (n = 2), disseminated (n = 2), lung-kidney (n = 1), and bone-muscle (n = 1). All patients were treated with prolonged amphotericin B therapy. Surgical debridement was employed in the three sinonasal infections. Death from mucormycosis occurred in ten of 13 (77%) patients. Two patients are alive, including one who had resolution of sinonasal infection. Mucormycosis may occur in both neutropenic and non-neutropenic patients, and may occur long after hospital discharge for BMT. These infections are often fatal, although patients with limited sinonasal disease may have a better prognosis, especially with early diagnosis and aggressive antifungal therapy. PMID- 8504273 TI - Effect of DMSO exposure without cryopreservation on hematopoietic progenitor cells. AB - Colligative cryoprotectants must be non-toxic at the high concentrations required for protection of cells from freeze-injury. Human hematopoietic stem cells are usually cryopreserved in a solution containing 1.6 molal (10% v/v) DMSO. We studied the chemical toxicity of this agent to myeloid and erythroid progenitor cells from healthy donors. No DMSO toxicity was found at concentrations of 5% or 10% at either 4 degrees or 37 degrees C for incubation durations up to 1 h. DMSO at 20% did not decrease the number of progenitor cell-derived colonies per 5 x 10(4) cells cultured, but did result in cell clumping during DMSO washout, resulting in a net loss of progenitor cells. At a concentration of 40% DMSO, a direct toxicity to hematopoietic progenitors was found. Delay in removal of DMSO after thawing of cryopreserved cells for periods up to 1 h was also non-toxic to hematopoietic progenitor cells. Direct addition of DMSO at 1% or 10% final concentration (v/v) to the culture dishes suppressed colony formation. These data suggest that DMSO is not toxic to haematopoietic progenitor cells after short term exposure at the concentrations used for cryopreservation of marrow and peripheral blood stem cells. PMID- 8504274 TI - Immunotherapy with interleukin 2 after ABMT in AML. AB - Myeloablative chemo (+/- radio) therapy and rescue with ABMT has been used as final consolidation therapy in 18 patients with AML in first remission. In seven (6 autologous, 1 syngeneic) marrow reinfusion was followed by iv IL-2. One patient, who commenced IL-2 4 days after BMT, died from pulmonary oedema due to the capillary leak syndrome. Thereafter, treatment with IL-2 was delayed until the platelet count reached 30 x 10(9)/l. All patients developed reversible hypotension (treated with infusion of colloid), but treatment was otherwise well tolerated. With 21-58 months (median 32 months) from the time of ABMT there has been one relapse (actuarial risk 17%, 95% confidence intervals (CI) 3-31%). The disease-free survival is 71% (95% CI 38-100%). Eleven patients with comparable remission induction and consolidation therapy, and an identical interval between diagnosis and ABMT (5-11 months, median 6 months) received an autograft without immunotherapy. With 24-45 months (median 29 months) follow-up the actuarial disease-free survival is 36% (95% CI 8-64%), the actuarial relapse risk is 54% (95% CI 18-90%). We conclude that immunotherapy given after ABMT to patients with AML in first remission when the platelet count exceeds 30 x 10(9)/l is safe and may induce an immunological environment which results in the elimination of residual leukaemia. PMID- 8504275 TI - Pentamidine aerosol for prophylaxis of Pneumocystis carinii pneumonia after BMT. AB - Following BMT there is a 5-15% risk of interstitial pneumonia caused by Pneumocystis carinii (PcP). Cotrimoxazole is therefore administered prophylactically, but may cause myelodepression, allergic reactions and nephrotoxicity. As PcP prophylaxis with pentamidine aerosol is effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate toxicity, safety, practicability and possible resorption of aerosolized pentamidine. We treated 31 allogeneic and 12 autologous BMT patients with 60 mg pentamidine 3 days before and 14 days after BMT. Starting 4 weeks after BMT, 300 mg pentamidine was given every 4 weeks for 6 months. There was no pneumonia caused by Pneumocystis carinii. The only noteworthy side-effects were cough (19.8%), salivation (9.6%), and sore throat (5.7%), of similar frequency after allogeneic or autologous BMT. Using high pressure liquid chromatography, pentamidine could only be detected in the serum of 33-54% of patients tested. In these patients the median serum levels were 7.5-9 ng/ml. We conclude that pentamidine aerosol has only minor side effects, is well tolerated and safe, and is therefore an attractive alternative for PcP prophylaxis after BMT. PMID- 8504276 TI - Inappropriate antidiuretic hormone secretion (SIADH) preceding skin manifestations of disseminated varicella zoster virus infection post-BMT. AB - We report the syndrome of inappropriate antidiuretic hormone secretion (SIADH) preceding the development of skin lesions of varicella zoster virus (VZV) infection in a patient with CML 5 months post-allogeneic BMT. This is the first report of SIADH complicating disseminated VZV infection in a BMT patient. SIADH is an unusual complication that may precede VZV infection post-BMT. PMID- 8504277 TI - Transfer by BMT of IgG2 deficiency involving an immunoglobulin heavy chain constant region deletion and a silent IgG2 gene. AB - A patient suffering from ALL who underwent allogeneic BMT developed complete IgG2 deficiency after BMT. When the donor Ig serum levels were examined, it was found that he also lacked detectable levels of IgG2. The IGHC genes were investigated and a heterozygous 50-70 kb deletion encompassing the genes coding for IgG2 (G2) and IgG4 (G4) (del G2-G4) was found in the white blood cells. The patient had IgG2 levels in the low normal range before BMT. When the patient's fibroblasts were examined to determine his original genotype, they were found to carry the same deletion haplotype, but in combination with a different G2 allele than that present in the transplanted BM cells. The combination of Ig heavy chain constant region gene alleles found in the transplant has also been inherited by a third brother also lacking IgG2. The hemizygous G2 allele present in the donated BM cells was thus 'silent' and the complete IgG2 deficiency had been transferred by the BMT. PMID- 8504278 TI - Pregnancy after BMT: three case reports. AB - A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen. PMID- 8504279 TI - N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate: synthesis and potential utility for the radioiodination of monoclonal antibodies. AB - N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate (MATE) was synthesized in two steps from 4-methyl-3-iodobenzoic acid. Radioiododestannylation of MATE proceeded more slowly than N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE), but for reaction periods of 10 min or more, identical yields were obtained. Paired-label biodistribution studies were performed in mice with an intact monoclonal antibody and an F(ab')2 fragment labeled using MATE, ATE and Iodogen. Thyroid uptake with MATE was low, comparable to that seen with ATE, and considerably lower than that observed when the Iodogen method was used. With the F(ab')2 fragment, kidney uptake using MATE was 8-fold higher than that observed when either the ATE or Iodogen methods were used. PMID- 8504280 TI - Determination of the target volume of HeLa cells treated with platinum-195m radiolabeled trans-diaminedichloroplatinum(II): a comparison with cis diaminedichloroplatinum(II). AB - HeLa S-3 cells were treated with 195mPt-radiolabeled trans diaminedichloroplatinum(II) (TDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with TDDP at 37 degrees C for 1, 2 and 3 h were 163.7, 65.8 and 24.9 microM, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules was determined after the cells were fractionated using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes, expressed as the reciprocals of the D0 values, were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t-RNA), under some limited condition, could be the target molecules for cell killing by TDDP. The target volumes for DNA were 1.31 x 10(3), 3.01 x 10(3) and 6.26 x 10(3) nucleotides for 1, 2 and 3 h treated cells, respectively. Cell killing effects of TDDP were lower than CDDP by a factor of 39.5, 19.0 and 16.5 for 1, 2 and 3 h treatments at 37 degrees C, respectively, when viewed from the stand point of the target volume, while those from the mean lethal dose (D0) were 17.6, 9.8 and 6.7, respectively. PMID- 8504281 TI - [99mTc] Teboroxime and [99mTc]Cl(DMG)3B2MP: binding characteristics andmetabolism of two [99mTc]BATOs in blood and tissues. AB - Studies were performed in vitro and in vivo to evaluate the binding properties and metabolism of [99mTc]Cl(CDO)3BMe (Teboroxime) and [99mTc]Cl(DMG)3B2MP in blood and target tissues of rats. Both radiopharmaceuticals displayed rapid binding (within 1-3 min) with high affinity to plasma proteins and blood cells. The amounts of radioactivity associated with blood components became progressively greater with time of exposure to either compound. There was a higher proportion of the radiopharmaceuticals associated with blood components during in vivo conditions, likely due, at least in part, to clearance of the free fraction from the plasma pool. Exposure of both compounds to blood results in axial ligand exchange of the chloro atom to a hydroxyl. The results suggest that it is the free species that is extracted primarily by tissues. PMID- 8504282 TI - Preparation and in vitro evaluation of "no-carrier-added" 18F-labeled biotin. AB - This paper will describe the preparation of "no-carrier-added" 18F-labeled biotin where the radiolabel bound to an aromatic moiety is described. This has been accomplished by preparation of [18F]fluorobenzylbromide (yield 20-30%) and its reaction with biotin-LC-hydrazide. This yielded "no-carrier-added" radiolabeled biotin (5-10%) which was then purified by reversed phase HPLC. The pure product was found to bind to avidin, thereby demonstrating retention of its biological integrity. Thus this product is potentially useful for imaging tumor tissue following injection of avidin coupled MoAbs. PMID- 8504283 TI - Tumor imaging with technetium-99m-DTPA encapsulated in RES-avoiding liposomes. AB - For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In the present study, we encapsulated technetium-99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA) in PGlcUA-liposomes (dipalmitoylphosphatidylcholine:cholesterol:PGlcUA = 40:40:20 as a molar ratio) and studied the biodistribution of the liposomes in tumor-bearing mice. 99mTc-DTPA encapsulated in liposomes effectively accumulated in tumor tissues after intravenous administration. Corresponding to these results, tumor was strongly imaged by a gamma-camera when 99mTc-DTPA-encapsulated PGlcUA liposomes were used. PMID- 8504284 TI - Cysteine, a chelating moiety for synthesis of technetium-99m radiopharmaceuticals -Part IV. Benzyl cysteine and derivatives. AB - To explore the possibility of utilizing cysteine derivatives for technetium-99m radiopharmaceutical preparation with clinical potential, we synthesized two benzyl substituted cysteine compounds, namely, S-benzyl cysteine 1 and cysteine benzyl ester 3. It was expected, from our previous studies on benzoyl cysteines, that the above two ligands after chelation with 99mTc would be excreted by the hepatobiliary pathway. Although for 99mTc-3 the above expectation was realized, 99mTc-1 behaved in a most unexpected way by affixing itself with kidney and selecting the renal tubular secretory pathway for its excretion. It is anticipated that the affinity of 99mTc-1 for kidney is due to its interaction with the kidney sulphhydryl group and it also formed an adduct with other sulphydryl containing compounds like thiophenol. In terms of the kidney-to background ratio, 99mTc-1 showed some superiority over other kidney structure agents, like 99mTc-dimercaptosuccinic acid and 99mTc-glucoheptanoic acid and, therefore, the chelate (99mTc-1) may have the potential to replace the above two radiopharmaceuticals in clinical use. PMID- 8504285 TI - Synthesis and evaluation of 1-[11C]methyl-4-aryl-piperazinium salts as myocardial imaging agents. AB - Our previous study with radioiodinated 1-methyl-1-(2-hydroxyethyl)-4- phenylpiperazinium derivatives indicated that these compounds localize selectively in the rat myocardium. Based upon these results, 1-[11C]methyl-1 alkyl-4-phenylpiperazinium cations were synthesized and evaluated for their potential as myocardial imaging agents. Biodistribution studies were performed in rats and imaging studies in normal dogs. The results indicate high concentrations of 3-4% ID/g in the rat heart at 5 min, comparable to those obtained with the radioiodinated analogs. Sequential imaging of the canine heart showed a similar pattern of uptake. The level of activity reached at 20 min was maintained over the 1-h time period. These results suggest that the phenylpiperazinium agents may have potential application as myocardial imaging agents. PMID- 8504286 TI - Biodistribution of anti-CEA F(ab')2 fragments conjugated with chelating polymers: influence of conjugate electron charge on tumor uptake and blood clearance. AB - F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) were modified with three chain-terminal polylysine-based chelating polymers so as to carry different electron charges. Immunoreactive conjugates labeled with 111In up to a specific radioactivity of 120-140 microCi/micrograms were injected into nude mice bearing human colorectal carcinoma, and the biodistribution patterns were compared with each other and with that of an anti-CEA F(ab')2-DTPA control. Immunoconjugate modified with positively-charged polymer produced the highest tumor uptake [up to 20% injected dose per gram (ID/g)], with very significant non-specific radioactivity in normal organs (particularly kidneys). When modified with a polymer carrying only a slight negative charge, the immunoconjugate also produced fairly high tumor uptake (up to 18% ID/g), with much lower non-specific radioactivity in normal organs. Highly negatively-charged conjugate produced the lowest tumor uptake (up to 8% ID/g), whereas blood and whole-body clearances were the fastest but slower than those of conventionally labeled F(ab')2 mAb. The possible mechanisms for the effects described are discussed. PMID- 8504287 TI - Preparation and biological evaluation of radiolabelled antibodies with selected carbohydrate modifications. AB - Two carbohydrates, N-acetylgalactosamine (GalNAc) and galactose-beta-1,3-GalNAc have been attached to human IgG (hIgG) by a novel linking reagent, hexafluoroglutaric acid dimethyl ester. Fluorine-19 NMR signals were used for the determination of the conjugation ratio. A third carbohydrate, sialic acid, was conjugated via reductive amination and the conjugation ratio determined by a resorcinol assay. The biological behaviour of these radioiodinated antibodies with carbohydrate modifications in normal mice indicates an enhanced liver uptake at 15 min post-injection with an associated change in circulating blood levels occurs for the galactose-based hIgG preparations. However, no significant differences in the biodistribution were observed for the sialic acid conjugate. These studies confirm the potential of carbohydrate-antibody conjugation for modifying the behaviour of antibodies in immunoscintigraphy and radioimmunotherapy. PMID- 8504288 TI - Evaluation of copper-labeled bifunctional chelate-albumin conjugates for blood pool imaging. AB - 62Cu(T1/2 = 9.8 min) is a generator-produced positron-emitting radionuclide with a half-life amenable to blood-pool imaging with PET. Three bifunctional chelates [cyclic anhydride of diethylenetriaminepentaacetic acid (cDTPAA), 6 bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N ',N", N"'-tetraacetic acid (BAT), and p-carboxyethylphenylglyoxal-bis-(4N-methyl-thiosemicarbazone (CE DTS)] were conjugated to HSA and labeled with 67Cu. The labeling efficiency of 67Cu-DTS-HSA was > 90%, whereas the labeling yields of 67Cu-DTPA-HSA and 67Cu benzyl-TETA-HSA were less than 70%. Blood clearance and biodistribution of these three 67Cu-labeled conjugates were determined in rats. Of the three 67Cu-labeled bifunctional chelate-HSA conjugates, 67Cu-benzyl-TETA-HSA remained in the blood pool the longest, achieving stable blood levels at times longer than 24 h post injection. The 67Cu radioactivity cleared the blood within 60 min post-injection of 67Cu-DTS-HSA, and within 10 min after administration of 67Cu-DTPA-HSA, indicating the dissociation of Cu2+ from these conjugates. Copper-labeled DTS-HSA achieved stable blood concentrations for at least 30 min post-injection and was therefore evaluated as a vascular imaging agent. DTS-HSA and benzyl-TETA-HSA were labeled with 62Cu and administered to a dog for blood-pool imaging using PET. Images were nearly identical to an image taken after administration of C15O. Because of the high labeling efficiency, DTS-HSA can be labeled with 62Cu without purification, making it more practical than 62Cu-benzyl-TETA-HSA as a blood-pool imaging agent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504289 TI - Radioiodinated 2-nitrobenzyl carbamates as bioreductive alkylating agents for tissue hypoxia. AB - Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [125I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo liability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumour-bearing mice showing limited uptake of radioactivity in tumours and a tumour-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents. PMID- 8504290 TI - Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice. AB - [11C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [11C]CH3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [11C]methamphetamine was investigated in the mice brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [11C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [11C]methamphetamine. PMID- 8504291 TI - Determination of estrogen 3-sulfates in biological fluids of mammary tumor bearing rats by radioimmunoassay. AB - Determination of estradiol 3-sulfate (E2 3-S) and estriol 3-sulfate (E3 3-S) in plasma, urine or tumor tissues of mammary tumor-bearing rats were performed using the superior radioimmunoassay (RIA) system. The plasma level of E2 3-S after tumorigenesis was found to be about one-third of the normal level. As to E3 3-S, the levels in urine were significantly high both before and after tumorigenesis. Before that, the average level was about 1.5 times, and after that, about 2.5 times as high as the normal level. In tumor tissues, an extremely high level of E3 3-S (399.6 +/- 113.9 pg/g tissue) was determined. PMID- 8504292 TI - Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides. AB - Three iodinated benzamides, 5-7, analogues of the potent acetylcholinesterase inhibitor 1-benzyl-4-[N-[4'-(benzylsulfonyl) benzoyl-N methylamino]ethyl]piperidine (2), were synthesized and evaluated as potential anticholinesterase agents. All three compounds were found to be three orders of magnitude less potent than the parent compound. However, receptor screening revealed that compounds 5-7 exhibit nanomolar affinity for the sigma binding site. Both [125I]5 and [125I]7 were synthesized and evaluated in rats. Following the intravenous administration of [125I]5 into rats, 1.59% of the injected dose was found in the rat brain within 5 min. The level of radioactivity in the brain remained steady for 2 h, the duration of the study. In contrast, 0.42% of the injected dose was detected in the rat brain following the i.v. injection of [125I]7. Coadministration of either [125I]5 or [125I]7 with 0.5 mumol/kg of haloperidol resulted in a 56-73% reduction in the level of radioactivity in the rat brain, suggesting that these compounds bind to the sigma binding site in vivo. Planar imaging studies with [123I]5 revealed significant accumulation of radioactivity within the monkey brain, with a half-life of 6 h. Compound [123I]5 may be potentially useful for studying sigma receptor distribution in the human brain. PMID- 8504293 TI - Preparation and preliminary biological evaluation of [18F]NCQ-115: a new selective reversible dopamine D2 receptor ligand. AB - 18F-labeled dopamine D2 antagonist, NCQ-115 ((+)-(R)-5-bromo-N-((1-(fluorobenzyl) 2-pyrrolidinyl)-methyl-2,3- dimethoxybenzamide), was successfully prepared using a remotely controlled system. [18F]Fluoride was reacted with the trifluoromethanesulfonate salt of 4-(trimethylamino)benzaldehyde. The product was first reduced with LAH, and then reacted with thionyl bromide to yield 18F labeled 4-fluorobenzylbromide. [18F]4-Fluorobenzylbromide was then reacted with the pyrrolidie precursor (NCQ-282) to yield the product [18F]NCQ-115 contaminated with unreacted starting material. The product was purified by reverse phase chromatography yielding [18F]NCQ-115 with a specific activity of more than 1400 Ci/mmol. Autoradiographic and biodistribution data following injection of [18F]NCQ-115 in rats revealed the regional uptake of striatum/cerebellum to be 3.2 at 30 min post-injection. PMID- 8504294 TI - [Roster of the Academy and program of meetings]. PMID- 8504295 TI - The Huntington disease gene--still a needle in a haystack? PMID- 8504296 TI - Spectrum of growth hormone receptor mutations and associated haplotypes in Laron syndrome. AB - Laron syndrome is a rare autosomal recessive disorder characterized by resistance to growth hormone (GH). In 10 patients of different ethnic origins, we have analyzed all the GH receptor (GHR)-coding exons along with their splice junctions and 6 intragenic polymorphic sites defining several GHR gene haplotypes. This allowed us to identify the mutations in the 20 chromosomes studied and to describe a new GHR haplotype. Eleven different mutations associated with various GHR haplotypes were observed; they included 3 nonsense mutations, 3 splice defects and 5 missense mutations. Of the 11 mutations, 8 were novel. All the mutations involved the exoplasmic domain of the receptor and all the missense mutations were clustered in a short polypeptide segment. Most of the missense mutations affected residues conserved among GHRs from different species and the related molecules that belong to the cytokine receptor superfamily. Adding to the 5 mutations so far described, these findings illustrate the allelic heterogeneity of this syndrome and document the independent origin of the molecular defects, all features of clinical relevance for genetic counselling. PMID- 8504297 TI - Genomic organization, chromosomal localization and promoter function of the human zinc-finger gene pAT133. AB - We report the genomic structure and chromosomal localization of the human zinc finger gene pAT133. This gene belongs to a family of four human immediate-early genes (pAT133, pAT225/EGR1, pAT591/EGR2 and EGR3), which have almost identical zinc-finger domains, but distinct flanking regions. The human pAT133 gene is organized in two exons, and has been mapped to human chromosome 2p13. We determined the transcription start site by primer extension analysis and identified several regulatory elements in the upstream regulatory sequence. The pAT133-promoter functions as an inducible promoter in human T cells and in fibroblasts, as constructs containing the bacterial chloramphenicol acetyl transferase (CAT) gene driven by a 943 bp pAT133-promoter fragment were induced in these cells by stimulation with PHA/PMA or by serum, respectively. The serum inducible pAT133-promoter lacks consensus serum response elements. However, we could demonstrate that two CArG-like motifs with a single base exchange confer serum inducibility to a reporter construct. Due to their serum responsiveness, these elements may serve as a high affinity binding sites for the recently described human serum response factor-related proteins. PMID- 8504298 TI - Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. AB - Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described. The KAL gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization recently determined. We have searched for mutations of the KAL gene in 21 unrelated males affected by familial Kallmann syndrome. In these families, segregation of the disease was suggestive of the X-linked mode of transmission. In 2 families, large Xp22.3 deletions, both including the entire KAL gene, have been detected by Southern blot analysis. Here we report the sequence analysis of the entire coding region of the KAL gene in the 19 remaining patients. The approach consisted of sequencing each of the 14 coding exons and splice site junctions. Each exon was amplified by PCR on the genomic DNA, using oligonucleotides from the flanking intronic sequences as specific primers. Nine point mutations were identified at separate locations in four exons and one splice site, providing strong evidence for heterogeneity in mutations responsible for the X-linked Kallmann syndrome. In addition, the high frequency of unilateral renal aplasia in X-linked Kallmann patients (6 out of 11 males with identified alterations of the KAL gene) should be emphasized. PMID- 8504299 TI - Cloning of the human and murine ROM1 genes: genomic organization and sequence conservation. AB - Rom-1 and peripherin are related membrane proteins of the photoreceptor outer segments. Both proteins are located at the rims of the photoreceptor disks, where they may act jointly in disk biogenesis. Mutations in the gene (RDS) encoding peripherin cause autosomal dominant retinitis pigmentosa, autosomal dominant punctata albescens and butterfly macular degeneration in man, and retinal degeneration slow in mice. To facilitate ROM1 mutation and linkage analysis in inherited retinal diseases, we cloned and characterized the human and murine ROM1 genes. In both species, the ROM1 coding region is contained within approximately 1.8 kb of genomic DNA and is interrupted by only two introns. The structures of the ROM1 and RDS genes are similar, with perfect conservation of the intron splice sites. Putative transcription regulatory regions of the ROM1 locus, 5' to an apparent transcription start site, were identified by cloning the mouse Rom-1 gene and comparing the sequence to the human homologue. Alignment of the human and murine rom-1 predicted protein sequences with the peripherin polypeptides of four species reveals a high degree of conservation (47% overall identity between the six proteins) in the central hydrophilic domain of the two family members. Despite this conservation of sequence, the predicted pI's of only this region of rom-1 and peripherin differ substantially, being 5.2 and 8.2, respectively. The charge difference in this region may mediate the non-covalent association of these two proteins in vivo. The conserved genomic structure and sequence of ROM1 and RDS indicates that these genes evolved from a common ancestor by duplication event. PMID- 8504300 TI - Alternative splicing in the fragile X gene FMR1. AB - The FMR1 gene, associated with fragile X syndrome, has recently been cloned and the sequence of partial cDNA clones is known. We have determined additional cDNA sequences both at the 5' and 3' end. We have characterized the expressed gene by means of RT-PCR in various tissues and have found that alternative splicing takes place in the FMR1 gene, which does not seem to be tissue specific. When the different alternative splicing events are combined, 12 distinct mRNA products could result from FMR1 expression in each tested tissue. In all these transcripts the open reading frame is maintained until the same stop codon. At the 3' end alternative use of polyadenylation signals is found. The alternative splicing allows functional diversity of the FMR-1 gene. Whether all the possible proteins will be synthesized and whether they will be functionally active has to be determined. PMID- 8504301 TI - A study of the origin of 'shadow bands' seen when typing dinucleotide repeat polymorphisms by the PCR. AB - Dinucleotide repeat polymorphisms ('microsatellites') are usually typed by resolving the products of PCR amplification on denaturing acrylamide gels. With this methodology, an allele consists not of a single fragment, but rather of a ladder of fragments, typically separated by intervals of 2nt. Mechanisms that have been invoked to explain the generation of these 'shadow bands' include slipped strand mispairing occurring during the PCR and artefactual 'recombination' caused by out-of-register annealing of truncated PCR products. The D11S527 locus contains the microsatellite sequence (GT)n(CTGT)m. By performing direct sequencing of PCR products derived from individuals homozygous at D11S527, we show that these products vary in length due solely to variations in the length of the dinucleotide repeat tract. These results rule out PCR recombination and support slipped strand mispairing as the major mechanism for generation of shadow bands. PMID- 8504302 TI - The genomic organisation of the human pseudoautosomal gene MIC2 and the detection of a related locus. AB - The human pseudoautosomal gene MIC2 encodes a 185 amino acid cell surface antigen recognised by the monoclonal antibody 12E7. The gene is abundantly expressed in all tissues tested and a role in cell-cell interactions has been suggested. We describe here the isolation of 95kb of genomic DNA encompassing the entire MIC2 gene. The gene is 52kb in size and orientated towards the centromere. As predicted by previous genetic studies, the 5' end of MIC2 is located 95kb from the pseudoautosomal boundary and confirming that the elevated rate of recombination in pseudoautosomal region is continuous up to the boundary. The gene is divided into ten exons which show correlation with predicted domains of the protein and are considerably smaller than the average for mammalian genes. Evolutionary studies indicate that the gene can be detected by DNA hybridisation only in primates, however genomic probes for both exons 1 and 5 detect related locus present on both the human X and Y chromosomes. PMID- 8504303 TI - Fucosidosis: four new mutations and a new polymorphism. AB - Fucosidosis is a rare lysosomal storage disease due to a nearly complete deficiency of alpha-L-fucosidase (EC 3.2.1.51). In this study, all 8 exons of the alpha-L-fucosidase structural gene (FUCA-1) were amplified by PCR methods, and the amplified products were subcloned and sequenced. Five patient groups with fucosidosis were selected according to their ethnic backgrounds and haplotypes for RFLPs in FUCA-1. Four presumptive disease causing mutations were detected: 1) A major deletion of DNA containing the last two exons of FUCA-1 in two Algerian siblings. 2) A G to T mutation in exon 6 resulting in an in-frame termination codon (E375X) in eight Hispanic patients from Colorado and New Mexico. 3) A G to A mutation (G60D) in exon 1 in four Italian patients and in three related French American (Cajun) patients. This G60D mutation creates a unique site for AflIII. 4) A frameshift mutation resulted from a two-base deletion in exon 2 (K151fs) in an Italian patient. This deletion obliterates a unique BstXI site and creates a new BpmI site, and was found in only this patient and in only one allele. The rationale for proposing these defects as disease causing mutations includes pedigree analysis and the predicted consequences of each defect upon the activity and the concentration of the enzyme. An A to G transition (Q281R) in exon 5 was found to be present in homozygous form in affected patients and also in normal subjects; it appears to be a newly identified polymorphism. It causes a charge change and may be responsible for the electrophoretic variant phenotype of fucosidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504304 TI - A polymorphic X-linked tetranucleotide repeat locus displaying a high rate of new mutation: implications for mechanisms of mutation at short tandem repeat loci. AB - We report a high rate of new mutation at a short tandem repeat sequence polymorphism (STR, microsatellite) at locus DXS981 on the proximal long arm of the human X chromosome. Among individuals of the CEPH pedigrees, new allele lengths are detected at this tetranucleotide repeat with a frequency of approximately 1.5%. In cases where the origin of the new allele was traceable, new mutant alleles at DXS981 varied by exactly one repeat length (4 bp) relative to that on the originating parental chromosome. Complete linkage disequilibrium between two additional insertion/deletion polymorphisms which closely flank the variation at the tetranucleotide repeat suggests that, to the extent that these new mutants are germline in origin, they are not generated by unequal exchange between homologues. Considered in light of the types of new mutations detected and the substantial linkage disequilibrium at this locus, these data have implications for the mechanism of variation at other loci containing short tandemly repeated sequences. PMID- 8504305 TI - Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2. AB - Modification of mammalian DNA by the methylation of cytosine in CpG dinucleotides is a complex phenomenon involved in a number of cellular and developmental processes. In particular, the characteristic hypermutability of CpGs may be a major contributor of point mutations leading to human genetic disease. We have hypothesized that DNA methylation contributes to mutations in the gene causing neurofibromatosis type 1 (NF1), one of the most common genetic disorders in humans and a disease where up to half of all cases are the result of sporadic germline mutations, usually in the paternally-derived allele. We have used two experimental approaches to analyze patterns of DNA methylation at CpG dinucleotides in the NF1 gene region. Southern analyses using isoschizomeric restriction pairs have revealed DNA methylation in areas flanking the NF1 gene region, while PCR-methylation assays have shown that methylation occurs both on genomic sequences flanking the NF1 gene and within the coding region of the gene itself. We suggest that methylated CpG dinucleotides within and around the highly mutable NF1 gene serve as a reservoir within which C-->T transitions contribute to the high frequency of spontaneous germline mutations associated with the disease. PMID- 8504306 TI - Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. AB - Human PDH complex deficiency is an extremely heterogeneous disease in its presentation and clinical course. In an investigation at the level of the gene into ten cases of PDH complex (E1) deficiency, we found that all had mutations in the coding sequence of the X-linked E1 alpha gene while the E1 beta coding sequence was normal. Six of these patients (three males, three females) had missense mutations resulting in a changed amino acid residue in the E1 alpha subunit at positions amino acid 148 (in two siblings), 170, 202, 234 and 263 of the mature protein. Two of the females had one normal E1 alpha gene and one with a deletion at the sites of tandem repeats of AGTAAGA and TAT respectively. The two remaining females also had one normal E1 alpha gene and one with an insertion. Both insertions, one of 2 bp and one of 4 bp, occurred in DNA hotspots normally associated with deletions. Only two of these ten mutations have been reported in other patients previously. In the five cases (including the two siblings) where parent DNA was available, only in one case could the same mutation be found in the patient as well as the maternal genomic DNA. PMID- 8504307 TI - Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe. AB - A candidate gene, OCRL-1, for the oculocerebrorenal syndrome of Lowe (OCRL) has been identified via positional cloning strategies. We have now developed RT-PCR techniques which allow amplification of nearly all of the open reading frame from total RNA and have used the PCR products for mutational analysis. Single strand conformational polymorphism analysis detected aberrant migration in two unrelated patients, both of whom were shown to have the same nonsense mutation at base 2746 on direct sequencing. An additional patient was found to be missing a segment from his RNA that corresponds to an entire exon. The identification of mutations in the OCRL-1 gene provides strong genetic evidence for its being the gene involved in Lowe syndrome. PMID- 8504308 TI - Loss of the 'azoospermia factor' (AZF) on Yq in man is not associated with loss of HYA. AB - We have typed 9 EBV cell lines from azoospermic or severely oligospermic patients for the expression of H-Y antigen, in order to test the hypothesis of the coincidence of AZF and HYA genes. Of nine patients with cytogenetically normal Y chromosomes, 7 could be tested for HYA expression and of these 6 were H-Y positive. Of the three patients showing Yq structural abnormalities, two could be tested for H-Y expression and one was negative, the other positive. These results therefore show no correlation between spermatogenic failure and the absence of HYA, thus separating the AZF locus from HYA. PMID- 8504309 TI - A four-nucleotide insertion hotspot in the X chromosome located pyruvate dehydrogenase E1 alpha gene (PDHA1). PMID- 8504310 TI - A novel fibrillin mutation in the Marfan syndrome which could disrupt calcium binding of the epidermal growth factor-like module. PMID- 8504311 TI - A simple and rapid PCR based method for AGU(Fin) determination. PMID- 8504312 TI - Lack of independence between five DNA polymorphisms in the NF1 gene. PMID- 8504313 TI - A silent A to G mutation in exon 11 of the medium-chain acyl-CoA dehydrogenase (MCAD) gene. PMID- 8504315 TI - Dinucleotide repeat polymorphism at the D14S99E locus. PMID- 8504314 TI - Dinucleotide repeat polymorphism in the Huntington's disease region at the D4S182 locus. PMID- 8504316 TI - Dinucleotide repeat polymorphisms at the D2S108 and D2S109 loci. PMID- 8504317 TI - A polymorphic dinucleotide repeat at the D10S141 locus. PMID- 8504318 TI - A polymorphic dinucleotide repeat at the ZNF22 locus. PMID- 8504319 TI - Dinucleotide repeat polymorphism at the D11S480 locus. PMID- 8504320 TI - Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene. PMID- 8504321 TI - The role of exercise in the treatment of inflammatory arthritis. AB - A routine of regular exercise is important in patients with inflammatory arthritis. Most patients with stage I and stage II RA are capable of engaging in an exercise program. Benefits include increased cardiovascular and muscle endurance, as well as improved muscle strength (Table 1). This in turn allows patients to function more independently and with an improved quality of life. Exercise programs are designed to restore range of motion, improve strength and endurance, and at the same time provide a social outlet and opportunity for improved self esteem. Exercises should progress slowly during which time patients should be closely monitored for symptoms of increased joint inflammation. PMID- 8504323 TI - Certification in sports medicine--improving the quality of care for all athletes. PMID- 8504322 TI - Selected surgical topics in rheumatoid arthritis. PMID- 8504324 TI - The future of rheumatoid arthritis treatment. AB - Research into the molecular mechanisms of immunological diseases and the development of more specific therapies are moving ahead simultaneously at a rapid pace. This information may provide a better paradigm for understanding the pathogenesis and the prospects for interventional immunotherapy of RA. PMID- 8504325 TI - Anterior knee pain--a symptom not a diagnosis. AB - A careful history and physical examination are the cornerstones of consistently successful diagnosis and treatment of anterior knee pain symptoms. Nonoperative treatment must be based on physical examination findings and should include both flexibility and strengthening. If an extended conscientious trial of nonoperative therapy fails to produce improvement, properly selected surgical procedures produce improvement in over 80% of cases. Realignment procedures, including lateral release, should only be proposed when malalignment can be documented. Although anterior knee pain has been called the "low back pain of the knee" by frustrated clinicians, effective treatment is likely when these principles are employed. PMID- 8504326 TI - The trachea: pathologic conditions and trauma. AB - A variety of common and uncommon conditions affect the trachea. Respiratory symptoms rarely occur until there is a 50% narrowing of the trachea. Chondromalacia, sometimes seen in conjunction with congenital tracheoesophageal fistula, can be identified with fluoroscopy. Patients with tracheal narrowing who undergo general anesthesia are at great risk for life-threatening acute airway obstruction after removal of the tube. Tracheal narrowing is associated with calcified mediastinal and hilar masses in fibrosing mediastinitis. Tracheal widening has been reported in 30% of patients with pulmonary fibrosis. Primary tracheal neoplasms are rare. In adults 90% of such lesions are malignant, but in children 90% are benign; these benign lesions include squamous cell papilloma and hemangioma. Malignant involvement of the trachea is usually secondary to invasion from adjacent lung, larynx, esophagus or thyroid tissue. Because misplaced tubes are associated with several complications, the radiologist must confirm the location of all tubes. Displacement of the endotracheal tube from full extension to flexion averages 2 cm. Therefore, the tube's tip should be at least this far above the carina to avoid insertion of the tube into the mainstem bronchus. Malpositioning of feeding tubes may cause pneumothorax. Tracheal trauma may be missed unless the radiologist is highly suspicious, as would occur for patients with unresponsive pneumothorax. Observation of the hyoid bone above the third cervical vertebra suggests transection of the cervical trachea. PMID- 8504327 TI - Sonolucent peripancreatic masses: differential diagnosis and related imaging. AB - The most common cause of a sonolucent mass in the epigastrium is a pancreatic pseudocyst; however, several other conditions can simulate a pseudocyst on ultrasonography (US) scans. This pictorial essay illustrates the spectrum of conditions that may present in this fashion and demonstrates the use of other imaging modalities, such as colour-flow and pulsed Doppler US, computed tomography, magnetic resonance imaging and angiography, in their evaluation. PMID- 8504328 TI - Doppler ultrasonography in the early postoperative evaluation of renal transplants in children. AB - The renal ultrasonography (US) scans of 23 children who had recently undergone kidney transplantation were reviewed; the studies included Doppler US scanning of the arterial vessels at several levels. There were 43 studies for children whose postoperative course was normal; 16 studies were obtained during episodes of acute tubular necrosis and 21 during episodes of acute rejection. The upper limit of normal for the resistive index (RI) at the arcuate artery is higher (up to 0.79) for a pediatric renal transplant patient than for adults with normal kidneys, regardless of the age of the kidney donor. Therefore, elevation of the RI to 0.80 or higher or complete loss of diastolic flow always indicates a complication of transplantation. Abnormally high RI values were seen in patients with both acute tubular necrosis and acute rejection; however, the RI value as determined by US did not distinguish these two entities. In addition, in 7 cases of acute tubular necrosis and 12 of acute rejection the RI was normal (0.58 to 0.79). PMID- 8504329 TI - Ultrasonographic features of abdominal ectopic splenic tissue. AB - Ectopic splenic tissue may be congenital (an accessory spleen) or a result of traumatic autotransplantation (splenosis). The purpose of this study was to identify the features of ectopic splenic tissue in ultrasonography (US) scans. Selective spleen scintigraphy (with heat-denatured erythrocytes labelled with technetium 99m) was performed on 33 patients who had undergone splenectomy after trauma; the 25 (76%) for whom the results were positive subsequently underwent US. Of the 25 patients, 23 (92%) had one to five foci of ectopic splenic tissue; 62 of the 68 foci (91%) were in the left upper quadrant. US identified splenic tissue in 17 of the 25 patients (68%). All 44 foci visible with US were hypoechoic, and 33 of them (75%) exhibited acoustic enhancement or an incomplete hyperechoic rim or both. Nineteen of the foci revealed by US (43%) were smaller than 1 cm2. No criteria were found to permit differentiation of accessory spleens from splenosis. In three of every four patients who undergo splenectomy after trauma, ectopic splenic tissue eventually develops. Radiologists should be aware of this condition to avoid incorrectly diagnosing this ectopic tissue as metastasis, adenopathy or another solid tumour. US, in combination with selective spleen scintigraphy, permits a specific diagnosis without invasive procedures. PMID- 8504330 TI - Percutaneous transluminal biopsy of the biliary tract. AB - Percutaneous transluminal biopsy performed under fluoroscopic control uses interventional access routes and allows direct sampling of biliary tract lesions. The authors report their experience with this technique in 20 patients. The biopsy site was the gallbladder in 9 patients and the intrahepatic or extrahepatic bile ducts in 11. A suspected malignant lesion was the indication for biopsy in 17 patients; 3 patients underwent biopsy of the gallbladder mucosa during ablation therapy. The procedure was performed with the forceps (for 17 patients), brush (for 2) or "scrape" (for 1) technique; diagnostic material was obtained in all but one case. The sensitivity, specificity and overall accuracy of diagnosis in the patients with a suspected malignant lesion were 71%, 100% and 88% respectively. There were no false-positive results. In this series one major complication, hemobilia necessitating transarterial embolization, occurred after the scrape biopsy, and minor, self-limiting gallbladder hemorrhage occurred in one patient. This study shows that percutaneous transluminal biopsy is a reliable technique for examining a variety of biliary tract lesions and can lead to an accurate pathological diagnosis. PMID- 8504331 TI - Computed tomography for nontraumatic headache: current utilization and cost effectiveness. AB - A retrospective study was performed at two teaching hospitals--one in the United States and one in Canada--to determine the results of computed tomography (CT) examinations of the head in patients with nontraumatic headache. Of 1111 examinations performed over a 3-year period, 120 (10.8%) demonstrated an acute intracranial abnormality, such as hemorrhage, infarction or tumour; the frequency of such abnormalities was highest among inpatients and subjects over 40 years of age. Cranial and extracranial abnormalities, such as sinusitis and metastases to the calvarium, were found in 40 (3.6%) of the cases. Chronic abnormalities, such as cerebral atrophy or remote infarction, were the most significant findings in 202 (18.2%) of the cases. The cost of finding each case of acute intracranial abnormality was $5962 (US); for subarachnoid hemorrhage among patients in the emergency department, it was $15,837 (US). PMID- 8504332 TI - Magnetic resonance imaging in the diagnosis of dominantly inherited cerebello olivary atrophy: a clinicopathologic study. AB - To facilitate the study of cerebellar degenerative disorders, improved clinical diagnosis is needed. Cerebello-olivary atrophy is pathologically distinct, but until now its diagnosis has been thought to require postmortem examination. This condition was considered as a possible diagnosis in two patients from different families with dominantly inherited ataxia. The affected members of each family demonstrated a stereotyped, progressive, "pure" cerebellar syndrome, which began with gait ataxia followed years later by dysarthria and limb ataxia. The autopsy findings for the first patient's father revealed paleocerebellar and olivary atrophy, characteristic of cerebello-olivary atrophy. Magnetic resonance imaging (MRI) of the brain of both patients revealed medullary, vermian and, to a lesser extent, cerebellar hemispheric atrophy but a normal pons. Dominantly inherited cerebello-olivary atrophy was diagnosed in both patients. Characteristic clinical and MRI features thus permit a confident clinical diagnosis of dominantly inherited cerebello-olivary atrophy. Recognition of this entity during life should advance the classification of cerebellar degenerative disorders. PMID- 8504333 TI - Tears of the medial collateral ligament: magnetic resonance imaging findings and associated injuries. AB - For 23 patients with a surgically proven tear of the medial collateral ligament the findings from magnetic resonance imaging (MRI) of the knee were evaluated retrospectively. MRI revealed the tear in all cases, although when the injury was severe, distinguishing high-grade partial tears from complete tears was difficult. Physical examination had indicated a tear in 22 (96%) of the cases. A high prevalence of associated cruciate and meniscal injuries was seen (in 23 [100%] and 12 [52%] of the cases respectively). Tears of the fibular collateral ligament occurred in 13 (57%) of the patients and at least one bony infraction in 22 (96%); most of the infractions were in the lateral compartment. Infractions of the lateral femoral condyle were frequently geographic (in 14 [70%] of the 20 cases) or impacted (in 5 [25%]). The spectrum of injuries associated with tears of the medial collateral ligament was consistent with the findings of previous studies focusing on cruciate and meniscal abnormalities; the minor variations were likely due to the severity of valgus stress in this sample. PMID- 8504334 TI - Periosteal chondroma masquerading as osteochondroma. AB - The authors describe two cases of a lesion that closely resembled osteochondroma occurring at the posterior aspect of the distal femur in the popliteal region. Histopathologic examination after open biopsy revealed that the lesions were periosteal chondromas, and they were resected. Osteochondroma, particularly that undergoing malignant transformation, should perhaps be considered in the differential diagnosis of periosteal chondroma; the key to distinguishing between these two lesions is the separation of periosteal chondroma from the medullary portion of the bone by intervening cortex. PMID- 8504335 TI - A survey of Canadian residents in diagnostic radiology. AB - This survey of English-speaking Canadian residents in diagnostic radiology was conducted to assess the factors motivating their choice of specialty, their workload, their degree of job satisfaction and their expectations upon completing the residency program. Partial or complete replies were received from 109 of the 223 eligible residents. Many of the respondents (46 of the 84 who answered the question) had seriously considered radiology as a career during medical school, and 91 of the 109 respondents were satisfied or very satisfied with their residency programs. However, it is possible that those who were dissatisfied did not respond. The information from this survey should be particularly useful to those considering a residency in diagnostic radiology. PMID- 8504336 TI - Shoulder lipoblastoma: magnetic resonance imaging characteristics. AB - The authors describe the magnetic resonance imaging (MRI) characteristics of lipoblastoma of the shoulder in an infant. The appearance of the lesion in MRI scans correlated well with the pathological observation of lobules of immature adipose tissue surrounding masses of myxoid tissue. However, the MRI study of lipoblastoma is nonspecific, and the results of other radiologic modalities, such as plain radiography, ultrasonography and computed tomography, are essential for a confident diagnosis. PMID- 8504337 TI - Spinal epidural abscess: unusual CT and microbiologic findings. AB - The incidence of spinal epidural abscess is increasing. Its expeditious diagnosis is essential if treatment is to be effective. The authors present a case in which both the computed tomography appearance and the microbiologic observations were unusual. PMID- 8504338 TI - Manipulation by catheter of unopened LGM filter. AB - The use of the transfemoral and transjugular venous routes for placement of inferior vena cava filters is accepted practice. However, the transjugular route is associated with substantially higher rates of incomplete filter opening for the LGM Vena Tech filter (Vena Tech, Evanston, Ill.). The appropriate course of action when a filter fails to open is unclear from the literature. Current recommendations include close observation or placement of a second filter above the unopened device. The authors report a case in which an incompletely opened filter delivered through the transjugular route was directly manipulated with a multipurpose catheter. The filter opened sufficiently to provide stability and obviate the need for a second filter. The authors recommend that manipulation by catheter be considered as the first option at the time of placement should an LGM filter fail to open completely. PMID- 8504339 TI - Aggressive fibromatosis simulating congenital lung malformation. AB - Aggressive fibromatosis is a locally invasive, non-metastasizing tumour of fibrous origin and variable radiologic appearance. The authors describe a child with intrathoracic aggressive fibromatosis that mimicked congenital malformation of the lung. PMID- 8504340 TI - MRI diagnosis of a ruptured breast implant presenting as an infraclavicular mass. AB - The authors report a case of a ruptured breast implant presenting as an infraclavicular mass lesion. The findings of film-screen mammography, plain radiography, computed tomography and initial biopsy were nondiagnostic. Magnetic resonance imaging demonstrated the extent of the abnormality and permitted the correct diagnosis. PMID- 8504341 TI - Rapid triple-compartment wrist arthrography with diluted contrast medium. AB - Triple-compartment wrist arthrography is currently considered the optimal technique for evaluating carpal instability, because injection of contrast agent into the radiocarpal joint alone can fail to reveal ligamentous disruption due to a ball-valve tear. Unfortunately, triple-compartment arthrography can be time consuming for both the patient and the radiologist. This report describes a technique for rapid triple-compartment wrist arthrography with standard (as opposed to digital subtraction) fluoroscopy. This technique reduces the time necessary to perform the study to 30 to 45 minutes without sacrificing diagnostic accuracy. PMID- 8504342 TI - Residents' corner. Answer to case of the month #19. Colouterine fistula. PMID- 8504343 TI - [Perineal pain and lesions of the internal pudendal nerves]. AB - A number of chronic pain syndromes in the perineal area can be related to pudendal nerves suffering. The constancy of symptoms among various patients, and in duration for a particular one, alterations revealed by electrophysiologic studies, pain relief by diagnostic blocks, data from anatomic studies, preliminary results of medical and surgical applied therapies, give consistent arguments for possible organic lesions of pudendal nerves. PMID- 8504344 TI - [Loco-regional anesthesia and orthopedic surgery of the shoulder]. AB - Interscalene block can induce by itself anesthesia for shoulder surgery, if the opening does not reach the delto-pectoral site nor the shoulder-blade, but medical indications must be thoroughly talked over on account of the risk of phrenic paralysis with patients suffering from breezing trouble, and the surgical position that may disturb the anesthesiologist in case he has to increase anesthesia. A superficial cervical plexus block is required in anesthesia of the upper part of the shoulder. Regional anesthesia is quite useful too as a complement to general anesthesia, for it provides excellent postsurgical analgesia. A catheter may be inserted at the end of the surgical process through a nerve stimulator, but the patient does not tolerate it long, its efficiency greatly diminishes after the first day, and paresthesias may occur as after effects. Today we prefer set interscalene block before the patient is anaesthetized, searching for paresthesias with a thin needle: this process does not take long to install, it is relatively painless and provides excellent analgesia during the per and post-surgical period, until the next day with long acting local anesthetics. Not any complication happened in fifty patients for one year. PMID- 8504345 TI - [Functional rehabilitation and loco-regional anesthesia following surgical loosening of joint stiffness]. AB - The nature and frequency of knee-joint lesions and stiffness is indicated followed by description of treatment varieties and of postoperative physiotherapy. General anaesthesia as well as local and regional anaesthesia can be satisfactory. Under the provision that the anaesthetist is proficient in both and that there are no counter-indications, the choice should be left to the patient. Full and honest preoperative information of patients is therefore mandatory. PMID- 8504347 TI - [The detection of thromboembolism in orthopedic traumatology: the value and limitations of D-dimer determination by the latex method]. AB - We studied the usefulness of plasma D-dimer determination by a latex agglutination test used as a deep venous thrombosis (DVT) detection method in patients undergoing recent orthopaedic or traumatologic surgery. Asymptomatic patients with a level of D-dimer up to 1.5 micrograms/ml suffered phlebographic venous thrombosis in 49.3% of the cases. Because a predictive value of negative test of 0.77 the latex assay cannot be recommended for screening in symptomatic DVT. However, post operative measurement of cross linked fibrin derivatives in plasma may play a role in the selection of asymptomatic patients for venography. PMID- 8504346 TI - [Prehospital thrombolysis in the acute phase of myocardial infarction. Apropos of cases handled by the mobile intensive care unit,Argenteuil (Val-d'Oise) from 1988 to 1991]. AB - We have studied prehospital thrombolytic therapy in acute myocardial infarction administered by the mobile intensive care unit of the Argenteuil hospital (Val d'Oise), between 1988 and 1991, after having detailed the protocol used. Our results confirm the effectiveness of thrombolysis, showing a rapid improvement of pain and ST segment in 50% of cases. There is a significant saving of time between pain and thrombolysis when the treatment is started during the prehospital phase. At present, in accordance with Isis 3 study results, Streptokinase is the drug of choice with rtPA being reserved for cases with contraindications for Streptokinase. PMID- 8504348 TI - [The detection of gas embolisms in neurosurgery caused by joint monitoring with capnography and the Swan-Ganz probe. (Apropos of 7 patients operated on in the sitting position]. AB - The aim of this study was to detect per-operative venous gas embolism in neurosurgery using capnography coupled to the Swan-Ganz catheter method. Using both methods, our study, carried out on seven patients operated in the sitting position, showed an occurrence of air embolism in four cases. The diagnosis of air embolism was made on a rapid and progressive drop of FECO2 with, at the same time, a rise of the pulmonary arterial pressure. PMID- 8504349 TI - [Chemical neurolysis using alcohol (alcoholization) in the treatment of spasticity in the hemiplegic]. AB - Spasticity is a source of disability for the hemiplegic patient. It leads to various disorders influencing the quality of gait: at the lower limb varus equinus foot deformity, toe-claw and/or hip adduction with adductors spasticity. At the upper limb, flexion deformity of the wrist and the hand makes grasp and grip ineffective and spasticity of the Pectoralis Major muscle is considered as a main cause of sympathetic dystrophy. Neurolysis with alcohol injection in the nerve trunk or at the motor point destroys the gamma fibers and reduces spasticity, without impairing motor command. The effects on spasticity, motricity, and deformity of 33 chemical neurolysis with alcohol are analysed with a six months follow-up (27 hemiplegic patients, 28 to 62 years old, mean = 54.5). The authors have used 60% alcohol concentration. Sciatic nerve injection significantly reduces triceps spasticity (7/11), improves the range motion of the ankle, and allows the patient to take off the ankle device. Those fair results are still present at the fourth month after injection. Similar results are reported after injection of the obturator nerve for hip adduction deformity (2/3), median nerve injection for wrist and hand deformity (6/6). Pectoralis Major injection in the motor point is effective for 10 of the 13 cases, preventing sympathetic reflex dystrophy or contributing to its dramatic improvement. PMID- 8504350 TI - [Treatment of algodystrophies. The point of view of an anesthetist]. AB - Algodystrophy is a complex and heterogenous syndrome, better defined as a subtype of Reflex Sympathetic Dystrophy syndrome (RSD). The pathophysiological theory of RSD has been supported by basic studies and clinical efficacy of sympathetic blocks. Results may be good, but some of RSD are not responsive to sympathetic blocks, and distinction between sympathetic dependent and independent pain has been proposed as subtypes of RSD. Physiotherapy is an essential part of RSD treatment. Sympathetic blocks and other analgesic therapies are performed in order to permit painless action of the physiotherapy against sick limbs stiffness. The rule must be: no painful physiotherapy. Use of other kind of drugs has yet to be defined. Calcitonin is potentially beneficial, but must be given in combination with blocks. Some new treatments rise interesting fundamental questions and some of them are under evaluation. Psychological support is the third part of treatment of these chronic pain patients. Multidisciplinary organisation, as offered by pain centers, can help to understand this syndrome and to elaborate guidelines for diagnosis, treatment and research programs. PMID- 8504351 TI - [Tetraplegia and functional surgery of the upper limb: what anesthesia for what surgery?]. AB - Surgical rehabilitation of the upper limb in quadriplegia aims to restore prehension function. Surgical restoration always involves active extension of both elbow and wrist. Anesthesia, which first aim is to allow adequate surgical conditions, must adapt to the patient's disability. In this particular setting, regional anesthesia and especially brachial plexus block techniques represents our priority choice. PMID- 8504352 TI - [Loco-regional anesthesia for surgery of the shoulder]. AB - Regional anesthesia represents a selective approach in shoulder surgery. The following technics can be used: brachial plexus block, cervical epidural and intra-articular anesthesia. The advantages of each technique are discussed. PMID- 8504353 TI - [Chronic poisoning by depot theophylline]. PMID- 8504354 TI - [Initiation of the first French study of the bacterial epidemiology of nosocomial pneumonias. Report of the press conference organized on February 25, 1993 by Bristol-Myers Squibb laboratories]. PMID- 8504355 TI - [Shoulder surgery using a plexus block: for or against. Against]. AB - Brachial plexus block is an alternative and elegant procedure for shoulder surgery. Three main concerns have to be considered when this technique is planed. Firstly, large amounts of local anaesthetic solution are necessary to achieve complete blockade of the region especially when the deeper tissues of the shoulder are concerned by the procedure. Secondly interscalenic cervical plexus block produces homolateral phrenic paralysis and may impair respiratory function in patients at risk or when supplemental IV drugs are administered. Thirdly, when nerve lesions of different mechanisms including plexus block itself occur, the origin of the lesion may be difficulty related to its cause. Indications of cervical block are therefore to be considered cautiously when shoulder surgery is performed. PMID- 8504356 TI - [Why choose loco-regional anesthesia for knee surgery?]. AB - The advantages and disadvantages of both general and local or regional anaesthesia for knee surgery are presented and the patient characteristics enumerated. Regional anaesthesia reduces the frequency of postoperative thrombo embolic accidents, diminishes blood-loss and permits good postoperative analgesia. Thus it seems to achieve better results in respect to morbidity and mortality. It requires the patient's consent and acceptance by the surgeons as well as appropriate operating theater management. PMID- 8504357 TI - [Loco-regional anesthesia for knee surgery. A plea for limited use]. PMID- 8504358 TI - [Resuscitation of the multi-handicapped newborn infant. Ethical problems]. PMID- 8504359 TI - [Surgery of a giant nevus in children and anesthesia-resuscitation]. PMID- 8504360 TI - [Ether before Morton]. PMID- 8504361 TI - Assessing the postanesthesia patient. PMID- 8504362 TI - Patient-controlled analgesia in the intensive care unit. PMID- 8504363 TI - The use of neuromuscular blocking agents in critical care nursing practice. PMID- 8504364 TI - Physiology and treatment of hemorrhagic shock during the early postoperative period. PMID- 8504365 TI - Managing postoperative hypothermia, rewarming, and its complications. PMID- 8504366 TI - Transfer out of critical care: freedom or fear? PMID- 8504367 TI - Acute postoperative pain management: a comprehensive review and update. PMID- 8504368 TI - Effects of calcitonin on bone quality and osteoblastic function. PMID- 8504369 TI - The effects of menopause on longitudinal bone loss from the spine. AB - Two hundred and thirty women aged 45-66 years were divided into three groups according to their menopausal status and were followed to assess the changes in vertebral bone mineral density (BMD). These included 71 premenopausal, 42 perimenopausal, and 117 postmenopausal women. Menopausal status was assessed through menstrual history and plasma concentrations of 17 beta estradiol and luteinizing hormone. BMD was measured by dual photon absorptiometry between 2 and 5 times over an average period of 27 months, and annual rates of changes were calculated by linear regression. BMD decreased significantly (P < 0.0001) in the three groups during the follow-up. Mean (+/- SD) annual rate of change was -0.79 +/- 1.5% for premenopausal, -2.35 +/- 1.5% for perimenopausal, and -1.24 +/- 1.5% for postmenopausal women. There was no difference in the rates of bone loss between the perimenopausal group and the postmenopausal group within 3 years after menopause (1-2 years: -2.34 +/- 2.1%; 2-3 years: -1.9 +/- 1.5%). Thereafter, rates decreased exponentially with time since menopause to fall out at the same level as the premenopausal level. These longitudinal data indicate that vertebral bone loss begins before menopause and accelerates sharply during menopause to decline exponentially with time after 3 years. PMID- 8504370 TI - Spine and femur densitometry at the menopause: are both sites necessary in the assessment of the risk of osteoporosis? AB - The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early postmenopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the "at risk" category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39-48% of the women at risk had a normal femoral BMD. On the other hand, 24-37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7 +/- 3.8%) and femoral neck (-2.1 +/- 2.5%) than for the spine (-1.5 +/- 2.1%) and trochanter (-1.5 +/- 3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r = 0.34-0.58). Among the 21 women with a rapid vertebral bone loss, 48-67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1-0.71).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504371 TI - Predicting various fragility fractures in women by forearm bone densitometry: a follow-up study. AB - This is a follow-up of a previous study on the predictive power of bone mineral measurements; two more observation years have been added. A group of women (n = 1076) had their forearm bone mineral content (BMC) measured from 1970-1976. All fractures that occurred in 1975-1987 (13 years) were recorded. Four hundred sixty nine fragility fractures occurred during the collection period. Again, it was found that BMC at the distal end of the forearm is a good predictor of future fracture before the age of 70. The measurement at the proximal site (forearm shafts), however, in contrast to our previous study, has a capacity of predicting fracture also in the age group 70-80. BMC measurements were good predictors of vertebral crush fractures and trochanteric hip fracture but lesser predictors of fractures of the distal end of the forearm. In age groups 40-70, BMC was a stronger predictor of fracture than age, and the risk associated with a 1 SD decrease of BMC 6 was 3.2 for a hip fracture as compared with those without any fragility fracture, even when adjusted for age. In addition to BMC, low body weight was a fracture predictor. Body weight 5 kg below age-adjusted mean increased the risk of a trochanteric hip fracture by 30%. The data are used in hypothetical calculations of the effects of screening. PMID- 8504372 TI - Total and regional bone mineral content in women treated with GnRH agonists. AB - Changes in bone mineral content induced by GnRH agonists were investigated by measuring total body bone mineral content (TBBM) and regional bone mineral content (BMC) (arms, legs, trunk, pelvis) and densities with dual energy X-ray absorptiometry in 25 premenopausal women before and after a 6-month treatment with gonadotropin-releasing hormone (GnRH) agonists. Biological markers of bone remodeling, estrogens, luteinizing hormone, and follicle-stimulating hormone were also measured. Weight and body mass index increased significantly after treatment (P < 0.05), and TBBM, corrected for weight (TBBM/W), decreased (P < 0.001). The changes in BMC that we observed ranged from +2.5% to -6.9%. The greatest decrease in regional BMC occurred in the trunk (4.4%, P < 0.001), with TBBM decreasing by 2.1% (P < 0.001). No significant changes were observed in the limbs. Tartrate resistant acid phosphatase (TRAP) increased significantly after treatment (P < 0.001) and a significant negative correlation between TRAP and TBBM (P < 0.001) and between TRAP and estradiol (P < 0.001) were observed before treatment. The lack of changes observed in the BMC of the limbs indicate that GnRH agonists cause a preferential loss of BMC in trunk osseous structures, a situation similar to that of the first years of menopause. PMID- 8504373 TI - Correlates of intestinal calcium absorption in women 10 years past the menopause. AB - Because intestinal calcium absorption may be an important independent determinant of calcium balance and therefore bone mass, we have studied this factor and other potential predictors in 196 healthy postmenopausal women. Gut calcium absorption was measured in each subject by a stable strontium method and expressed as a fractional absorption. The fractional absorption was significantly negatively correlated with years since menopause (YSM) (r = -0.15 P < 0.05) and dietary calcium intake (r = -0.15 P < 0.05), and significantly positively correlated with 24-hour urine calcium excretion (r = 0.31 P < 0.001) and body mass index (r = 0.20 P < 0.01). Apart from YSM, these factors remained as correlates in multiple regression analysis; the standardized regression coefficient was largest for 24 hour urine calcium excretion (0.32). Fractional absorption of calcium was not correlated with vertebral bone density. Thus, intestinal calcium absorption, although falling with increasing menopausal age and increasing calcium intake, is best correlated with the urine calcium excretion. This indicates either that gut calcium absorption is regulated in response to the magnitude of the urine calcium excretion or that the kidney maintains calcium balance by excreting what is absorbed by the intestine. The mechanisms whereby gut and renal calcium handling are correlated are uncertain. PMID- 8504374 TI - Sustained release of salmon calcitonin in vivo from lactide: glycolide copolymer depots. AB - Studies were carried out to determine whether monolithic depot formulations, prepared using lactide:glycolide copolymers, could be used to administer salmon calcitonin (sCT) to rats in vivo. Formulations containing 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of peptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma calcium concentrations and cumulative weight gain of the animals were used to measure pharmacological effects of the released sCT. Release of sCT from the depots was controlled by the copolymer and was sustained for periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading of the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day period postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between days 11 and 18. Release of peptide from the depots was essentially complete by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have application for the convenient clinical administration of sCT in metabolic bone diseases. PMID- 8504375 TI - Differentiation and mineralization in osteogenic precursor cells derived from fetal rat mandibular bone. AB - The process of mineralization in cells prepared either by neutral protease digestion (Pro I) or by collagenase digestion (fifth cycle, Col V) from fetal rat mandible was studied in vitro. Alkaline phosphatase (ALPase) activity of cells in Pro I was low on day 3, increased rapidly from day 8, and reached a maximum on day 16, whereas that in Col V was high on day 2, then declined and thereafter elevated to reach a maximum on day 13. Both cell populations synthesized type I collagen in cell matrix and medium. Type III collagen was observed in cell matrix of Pro I on day 14 and 21. There was alpha 2 band of type V collagen in cell matrix of Pro I on day 21. Calcium deposition could be detected from day 14 in Pro I and from day 19 in Col V. The von Kossa-positive nodules were found on day 17 in Pro I and day 21 in Col V, respectively. The extracellular matrix in Pro I electron-microscopically consisted of well-banded collagen fibrils with a large number of calcified spherules. An elevation of ALPase activity, collagen synthesis, and mineral deposition occurred sequentially with a time lapse in Col V, and almost simultaneously in Pro I. The number of mineralized nodules was correlated with the density of plated cells in Pro I, but not in Col V. Dexamethasone caused an increase in the number of mineralized nodules in Pro I, but not in Col V, suggesting that Pro I contained osteoprogenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504376 TI - Influence of disodium (1-hydroxythylidene) diphosphonate on bonding between glass ceramics containing apatite and wollastonite and mature male rabbit bone. AB - It has been reported that bioactive glass-ceramics containing crystalline oxy- and fluoroapatite [Ca10(PO4)6(O,F2) and wollastonite (CaSiO3), chemical composition: MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF2 0.5 in weight ratio] bond to bone tissue through the formation of an apatite (a calcium and phosphorus rich layer) on the ceramic surface. In this study, the influence of disodium (1 hydroxythylidene) diphosphonate (DHTD) on the bonding between bone and glass ceramics containing apatite and wollastonite was investigated. Rectangular ceramic plates (15 mm x 10 mm x 2 mm, abraded with #2000 alumina powder) were implanted into the tibial bone of mature male rabbits. DHTD was administered daily by subcutaneous injection to groups 1-5: group 1-4 at doses of 20, 5.0, 1.0, and 0.1 mg/kg body wt/day for 8 weeks; and group 5 at a dose of 5 mg/kg body wt/day for 4 weeks. Group 6 was given injections of saline as a control. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the ceramics were dissected out and used for a detachment test. The failure load, when an implant became detached from the bone, or when the bone itself broke, was measured. The failure loads for groups 1-6 were 0 kg, 0 kg, 8.08 +/- 2.43 kg, 7.28 +/- 2.07 kg, 5.56 +/- 1.63 kg, and 6.38 +/- 1.30 kg, respectively. Ceramic bonding to bone tissue was inhibited by a higher dose of DHTD (groups 1 and 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504377 TI - The influence of fluoride on proteoglycan structure using a rat odontoblast in vitro system. AB - Using an in vitro rat incisor odontoblast system, the effect of fluoride on proteoglycans was investigated at both the metabolic and structural level. Incisors were removed from 4-week-old rats, split longitudinally, and the pulps removed. Teeth were incubated at 37 degrees C, 5% CO2 in Eagle's Minimum Essential Medium containing 35S-sulfate for 7 hours in the presence of 0 mM, 3 mM, or 6 mM sodium fluoride. Teeth were demineralized in EDTA, proteoglycan was extracted from the residue with 4 M guanidinium chloride, and further purified by anion exchange chromatography. Uptake of radiolabel was monitored by liquid scintillation counting. The resultant products were examined by cellulose acetate electrophoresis, SDS-PAGE, chondroitinase digestion, and amino acid analysis. Differential effects of fluoride were observed in both metabolism and biochemical characterization of proteoglycans following incubation at the two concentrations. Fluoride decreased uptake of the radiolabel but led to an accumulation of glycosaminoglycan within the proteoglycan of the matrix. Chondroitin sulfate was the predominant glycosaminoglycan identified, with the additional presence of dermatan sulfate and heparan sulfate identified. Dermatan sulfate levels increased in 3 mM-treated teeth. Fluoride-treated proteoglycans had a reduced molecular weight (200-90K to 180-79K); this reduction is primarily a result of smaller glycosaminoglycan chains, with limited reduction in the size of the core protein of 6 mM-treated teeth occurring. Such alterations in the biochemical metabolism and hence structure and function of proteoglycan may be implicated in the hypomineralization seen in fluorosis. PMID- 8504378 TI - The effects of diet, age, and sex on the mineral content of primate bones. AB - The effect of diet, age, and sex on the mineral content of primate bones was determined for free-ranging rhesus monkeys (Macaca mulatta) from the Caribbean Primate Research Center. Monkeys in this study were of known age and sex and had been provided with either a low protein (15%) or a high protein (25%) diet for most of their lives. Instrumental neutron activation analysis was used to assess bone mineral content. Results showed that diet had no significant effect on the bulk mineral composition of Ca, Mg, Br, and Cl in the bones. Of the minerals analyzed, only Na and Mn showed significant diet-related effects. The bone Ca content was found to be lower in females than in males when controlled for age. Finally, Ca content was found to be higher in young adults, lower at middle age, and higher in old age in both male and female monkeys. In conclusion, this study has shown that increasing protein content in the diet does not change the bulk mineral content of primate bones. The nondietary effect that Ca content of monkey bones is lower during middle age has not been previously reported. PMID- 8504379 TI - An overview of the older driver. AB - Although MVC rates are not substantially higher among older drivers after adjusting for mileage and may even be lower, the crash risk of the elderly driver remains a matter of increasing public concern. In part this is due to media attention over isolated cases of fatal MVCs involving older drivers, occasionally with a demented driver. This media attention has led to growing apprehension over the issue of elderly drivers. Physicians are likely to be involved increasingly in the evaluation of older drivers, whether they want to or not. The physician's quandary is the competing interests of the patient's well-being (i.e., continued independence), and the public's welfare (i.e., protection from impaired drivers). Unfortunately, there are no certain guidelines to protect the physician from liability for either of these conflicting duties. At issue is the foreseeability of harm from an elderly driver, either to self or to others. What degree of impairment is necessary before a physician is bound to report a patient to authorities? Although there are no clear answers, the best advice is to follow clinical judgment. One suggestion is to consider the diagnosis as suitable evidence. Thus, if the patient has a dementing illness of sufficient severity to warrant documentation in the medical record as a diagnosis, then perhaps the physician should consider advising the patient not to drive; reporting the patient to the appropriate authorities would be left to the physician's discretion after consultation with the patient's family. This might have the added benefit of obliging physicians to think twice before mislabeling patients with benign forgetfullness as demented, an all-too-frequent phenomenon. In this weighty ethical decision, it is critical for physicians to consider the consequences of removal of driving privileges from their elderly patients as well as their duty to protect the public health. Neither should be taken lightly. Above all else, physicians should not forsake their responsibility for advising either patients or the public regarding the driving privilege. To do so would simply relinquish the decision-making to those without clinical training or evaluative skills relevant to driving tasks. The physician's role in the evaluation of the elderly driver should be regarded as a pivotal challenge in the complicated management of the health of the elderly population. PMID- 8504380 TI - Transportation needs of the elderly population. AB - All evidence suggests that the elderly population of today and tomorrow will continue to depend on the private car to give them freedom, independence, and choice--as do younger travellers. Given the demographic changes in the United States, it seems very unlikely that other modes or options can provide anywhere near the level of mobility that the elderly want or need. Almost three fourths of those over age 65 will live in suburban or rural places after the turn of the century, places where transit and para-transit options are inherently impractical or costly. These elderly individuals will have made choices about doctors, hospitals, friends, and social and recreational options based on their lifelong access to the car. When they can no longer drive or receive rides, their mobility will drop and they may have to make drastic changes in their whole life network to be able to access just a few necessary services. Those concerned with the use of medical services by the elderly population must focus not only on transportation but on the other variables that create the need for a car. Transportation needs are clearly linked to where and how medical and social services are made available, so medical agencies must recognize the changing demographics of the elderly population by locating and programming their services accordingly. Medical and human service agencies will have to make an effort to make their programs accessible to the elderly population rather than simply locating their facilities where they please and assuming that elderly persons or transportation planners will somehow deal with the resulting loss of mobility. PMID- 8504381 TI - Evaluation of the elderly driver with arthritis. AB - Examination focusing upon the two clusters of function necessary for turning and braking is important as is nonthreatening questioning about driving. The effects of drugs used for arthritis on the CNS and a heightened emphasis upon the psychosocial implications of immobility complicate the management of older drivers with arthritis. Assuming optimal treatment of the arthritis, the two most important management tools are actually power-steering and automatic transmission. Less expensive adaptive available thorough rehabilitation services (e.g., auxiliary mirrors) are also of value. PMID- 8504382 TI - Seizure disorders, diabetes mellitus, and cerebrovascular disease. Considerations for older drivers. AB - For those conditions in which loss of consciousness is the main issue, such as epilepsy, factors that contribute to risk of seizure recurrence are central to the determination of driver safety. Thus, high- and low-risk groups may be identified and factors that contribute to high risk checked. These factors also serve to develop a program to reduce such risk in the future. In the population with seizure disorders, young males under age 25 have the highest risk for traffic accidents and violations. Other factors associated with high risk are partial complex seizure type, history of drug toxicity with anticonvulsant medications, alcohol abuse or poor compliance for medications, and history of psychiatric illness. For conditions such as cerebrovascular accidents or Parkinson's disease, the recognition of the diagnosis alone is insufficient to determine driver competence. In these illnesses, the task is to recognize levels of failure of individual skills and function that specifically render a person incompetent for safe driving. Such a precise determination is currently not possible in individuals with cerebrovascular accidents or other forms of brain injury (e.g., trauma) or degenerative brain disease (e.g., Parkinson's disease). There is intuitive and general agreement that there are those so severely affected that driving has become impossible or very dangerous. Alternately, there are also those with these conditions whose driving skills and competence are virtually unaffected and pose no risk to traffic safety. Physicians vary widely in their ability and experience in judging the competence and safety of those in between these two extremes. For this reason, a standardized approach is essential both to ensure the avoidance of unnecessary bias as well as to ensure the safety of the driver and the general public. At some time in the future when all the necessary driving skills are identified and appropriate tests are developed to judge them, a battery of tests for the elderly at age 65 and at regular intervals thereafter may be used. Until then, some form of clinical judgment and legal regulation may have to be adopted. One option would be to adopt a rule similar to that in the United Kingdom where all persons with TIAs or cerebrovascular accidents would automatically suspend driving for 3 months because of the high risk for recurrence of both cerebrovascular as well as ischemic heart disease in that interval.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504383 TI - Effects of cardiovascular disease on driving tasks. AB - Heart disease, even in the elderly individual, need not preclude driving; however, safety for the patient and the public is dependent on close cooperation between the patient and the physician. The patient with ischemic heart disease must be in a stable condition wherein the risk of sudden incapacitation is acceptably low. The physician must take into consideration not only the symptom history, but also the potential impact of concomitant illnesses, devices (e.g., pacemakers), and medications. The patient with congestive heart failure must be assessed for functional ability. Where there is doubt about a subjective report, a practical road test may be advisable. Consideration also should be given to limited driving under preset conditions, such as daytime only, or local roads (excluding highways). Many elderly drivers already limit their driving in such a fashion. Finally, it should be realized that a driving permit is a means to independent mobility. Where heart disease precludes driving and personal transportation is not available, physicians should advise and support their patients to obtain paratransport services where communities offer such services for otherwise immobile citizens. PMID- 8504384 TI - Dementia and the older driver. AB - Many demented patients continue to drive who, as a group, appear to be at increased risk for crashes, when compared with controls. Some studies have shown significant relationships between cognitive and functional measures, driver status performance on driving tests, and crash data. A number of methodologic problems in the studies reduce the level of confidence to which the data can be generalized. Diagnosis is not an adequate predictor of function. There is great heterogeneity of the rate of progress as well as the cognitive strengths and weaknesses among patients with dementing disorders. Performance-based guidelines for driving competence are essential rather than dependence on diagnostic labels. Ultimately, there would be no concern if there were no injury. There would be little concern if our cars and roadways were designed in such a way that the driver played little role in the traffic interaction. The potential for such systems exists but is expensive and unlikely to be built on a large scale. Therefore, it is necessary to identify the characteristics of the drivers who pose "unacceptable" risk to themselves and others. Functional information obtained from the family should be supplemented by an observational assessment of the patient, ideally by a trained specialist. The health care team's goal is to help the aging patient maintain autonomy in the face of declining health and psychosocial status. This outcome relies on a close alliance between physicians, nurses, occupational therapists, psychologists, social workers, and others to understand and manage the functional aspects and complex interactions between aging, disease, and social support systems. Treatment teams with skills in functional assessment and knowledge about the available social services are invaluable in caring for the functionally declining elderly patient. Recommendations to withdraw driving privileges on the basis of a diagnosis of dementia may ultimately be borne out by appropriate studies, but these studies have not been conducted. There is a great need for a consensus process to identify dangerous drivers, ideally with performance-based measures. This would then support uniform laws across the country that protect the patient, the physician, and the public. Education of the medical and lay community of the "warning signs" of declining driving skills could do much to heighten awareness in the community, much as the warning signs of cancer have been publicized. With the aging of our nation's population and the strong association of aging with dementing disorders, there is reason to be concerned, especially when dementing illnesses affect judgment. Demented drivers may pose a significant public health problem.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504385 TI - Geriatric assessment and driver functioning. AB - In this article, the sensory, cognitive, and motor function relevant to driving, their measurement, the epidemiology of age-associated functional impairments, and the relationship of functional impairments to both self-reported driving and the imposition of legal restrictions are reviewed. A number of issues remain to be resolved before the scientific basis for public policy recommendations on aging drivers is sufficiently sound. For example, although an association between various functional impairments and the imposition of restrictions was found, with the exception of visual impairments, which under Iowa law may require the imposition of restrictions, those aspects of functional impairment that precipitate state-imposed license restrictions cannot be identified by the authors. The authors' measures of functional status may serve as surrogates for other, more important variables. If so, it has implications for both prevention of impairment-associated restrictions and interventions occurring after restrictions have been imposed. One of the most important issues confronting clinicians, researchers, and regulators is the development of appropriate tests to screen for dysfunctional driving with safety risks. Whether an appropriate battery could be created from already-existing tests and questionnaires is unclear. Certainly it seems desirable to consider the issue of face validity and explore items more clearly related to driving, such as self-reported loss of concentration or difficulty with manipulating controls. Many of the current tests focus on low levels of cognitive and physical performance. Relatively severe impairments are clearly related to driving behavior, as the authors found. Relatively minor impairments also may have an impact on driving performance, however, and it is important to explore tests sensitive to these mild impairments. Finally, it is critical to conduct appropriate studies of the reliability, validity, sensitivity, and specificity of any proposed batteries. These studies should include representative samples of drivers and not just clinic populations or community volunteers. It is also important to include a number of assessments of driving. Although state records of accidents and violations are useful, not all accidents or violations are included in state records. From a public health standpoint, crashes are the outcome of interest, but their relatively low rates require large number s of research participants or relatively long study periods. More detailed driver assessments similar to those included in state on-the-road testing or course testing are also important.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504386 TI - Attention and driving. Assessment in elderly individuals with dementia. AB - Older drivers with dementia are involved in more crashes than healthy older drivers. Some investigators, therefore, have proposed that a diagnosis of dementia (DAT or other type) should lead to the automatic revocation of a driver's license. In the authors' view, however, renewal of license should be based on criteria related to driving competence rather than solely on chronologic age or a medical diagnosis. Unfortunately, current competency testing procedures do not assess the attentional factors discussed herewith that have been found to be important for safe driving. As the studies reviewed in this article reveal, there is good evidence that a skill test that predicts crash involvement in older drivers should incorporate attentional measures, in particular tests of attentional shifting based on dichotic listening and related tests. There is also evidence that attention-shifting measures are diagnostic of attention impairment in the early stages of Alzheimer-type dementia. Further research is needed to determine whether other attentional skills, such as sustained and divided attention, also need to be assessed. Additional work also is needed to refine attention tests for ease of use in the clinical setting. Lastly, although these attention measures account for only some of the variance contributing to crash involvement, they may allow for better predictive capability when combined with measures of other skills involved in driving. Driver training programs can complement driver testing procedures in serving the dual requirement for reducing crash risk among drivers with dementia while continuing to be responsive to their mobility needs. Information on the role of attention and other cognitive skills in safe driving should be made available, so that drivers (or their family members) who think they may have declining skills can seek further evaluation. Organizations such as automobile associations and retired persons groups can provide self-assessment inventories for completion by older drivers or referral for medical and neuropsychological evaluation. Finally, training techniques for improving attentional skills in drivers with DAT need to be developed and tested. PMID- 8504388 TI - Psychomotor mobility and the elderly driver. AB - In summary, declines in motor ability and reaction time are noted with aging, although the effect of these changes on actual driving performance needs further elucidation. It may be possible to compensate partially for some of these declines through physical and behavioral training. Attention to the physical, cognitive, and sensory capacities of older individuals in the design of vehicles and roadways also may be beneficial. Considerable work still needs to be done to adequately assess the changes that occur with aging in driving ability, what factors influence these changes and their potential modification, as well as the costs of any interventions planned. PMID- 8504387 TI - Assessing visual function in the older driver. AB - It is likely that some older adults will have to be restricted from driving because of serious and irreversible deterioration in skills crucial to driving, due to vision impairment, visual attention deficits, and decreased cognitive status; however many older adults with driving difficulties can improve their driving skills or reduce their crash risk through education or training programs. Research to evaluate interventions such as those previously mentioned has high priority, given society's need to maintain the mobility and personal independence of older adults without sacrificing safety concerns. PMID- 8504389 TI - Medications and the older driver. AB - Table 4 provides a summary of the evidence that specific medications adversely affect the safety of the older driver. The preponderance of evidence suggests that benzodiazepines adversely affect the safety of the older driver, particularly for high doses and long half-life compounds. This conclusion is based upon the very consistent psychomotor function data showing pronounced dose related impairment, the more limited epidemiologic data on crash involvement, epidemiologic data associating benzodiazepines with other types of injuries, and the fact that the reasons for most benzodiazepine use are not plausible confounders. This conclusion thus reinforces the need to prescribe benzodiazepines cautiously, including assessment of nonpharmacologic alternatives, use of the lowest possible dose for the shortest possible time, and avoidance of the very long half-life compounds. As more new nonbenzodiazepine anxiolytics and hypnotics become available, their effects on the safety of the elderly driver need to be determined. There is some evidence that cyclic antidepressants, currently the mainstay for treatment of depression in the elderly population, adversely affect driving safety; however, because of the paucity of experimental and epidemiologic data concerning the effects of depression per se on driving, further research is needed. Nevertheless, the existing data reinforce the need for careful prescribing of antidepressants, particularly avoidance of agents with high side-effect profiles (such as amitriptyline and imipramine) in the older driver. For hypoglycemics, although there is sufficient evidence of driving impairment to create a basis for concern, there are many unresolved questions. Currently, diabetic patients should be advised concerning the risk and management of hypoglycemia. For other sedating drugs, it always is prudent to advise patients concerning potential effects on driving. Unlike younger drivers, the typical older driver is a medication-taker. There now is a substantial body of evidence that commonly used medications can interfere with driving safety. Because many questions remain unanswered, there is a pressing need for further research that more fully elucidates how patient characteristics, disease, and drugs interact to affect driving safety; however, sufficient data are available to reinforce an underlying theme in geriatric medicine that is not yet fully implemented in practice: the need for caution in pharmacotherapy, with selection of a drug, dose, and regimen suitable for the unique characteristics of this population. PMID- 8504390 TI - Evaluation and retraining programs for older drivers. AB - Although many individuals who have had strokes or other physical problems assume that they can no longer drive, they are often unaware of retraining programs. In addition to formal courses supported by sponsoring agencies, such as the AAA, there are also programs run by occupational therapists. This article addresses issues relevant to the role of occupational therapists in evaluation and retraining of older drivers and describes several cases as examples. To better inform the public about driver retraining programs for the elderly and the disabled population, the American Occupational Therapy Association has published a pamphlet entitled Able Driving Is Safe Driving that provides information on how driving skills may be affected by age or illness. This publication also will provide examples of adaptive driving equipment usage and driver training. AOTA hopes this pamphlet will inform older adults of their options in maintaining independent community mobility. Research is needed to find out if older adults have relinquished driving because of a physical disability that may have been treatable with rehabilitation. Also, there needs to be a comparison study of classroom driving instruction to actual skill performance so that older adults and insurance companies are investing in programs that will demonstrate the outcome of improved driving performance. PMID- 8504391 TI - Assessment of older drivers. AB - As concern increases about the safety of the aging driver, it is clear that the principal goal of assessment is to identify the unsafe driver and provide effective medical and rehabilitative services to enable the resumption of safe driving. When adequate restorative therapy is not possible, it is necessary to restrict or revoke the privilege of driving. Assessment also can reassure the safe older driver that he or she can continue operating a motor vehicle without restrictions. The process of assessing the older driver is best accomplished through the collaboration of health professionals and governmental agencies. The former identify and treat, if possible, medical conditions that may pose threats to safe driving; the latter establish guidelines of competency for driving tasks. These roles are complementary, although the settings and methods for these assessments are different. Moreover, the responsibilities of the physician and other health care professionals extend beyond the decision regarding driving and must consider the individual needs for driving, as well as the ramifications associated with its cessation. PMID- 8504392 TI - Evaluation and treatment of the elderly trauma victim. AB - This article examined issues in the care of the injured elderly patient. Past studies have documented variable potential for functional recovery in survivors of serious trauma in the elderly population, and trauma care for this subgroup uses health care resources at an exaggerated rate. Excessive health care costs arise from increased postinjury morbidity and mortality in the elderly population; factors that predict mortality include injury severity, advanced age, and complications. Recent work has focused on the frequency of preventable complications, particularly critical care management errors, in trauma patients of all ages. It appears that the impact of preventable complications on mortality may be greatest in the geriatric trauma victim. Current recommendations for care of these patients include aggressive treatment of all injuries according to standard trauma practice. Routine ICU admission with a low threshold for the institution of invasive monitoring to guide therapy is recommended for all geriatric trauma victims with moderate to more serious injury. The development of specialized management approaches for care of the injured elderly patient will result from ongoing study of this population, as research efforts provide more information about the physiologic and metabolic responses to injury in the elderly population. PMID- 8504393 TI - Rehabilitation of the elderly crash victim. AB - In summary, the field of PM&R offers a focused interdisciplinary approach to the person with a disability and specifically to the older adult with functional limitations. The elderly crash victim presents with a multitude of problems that can be managed well in a geriatric rehabilitation setting, following acute management interventions. The importance of early assessment of social supports, living situations, physical abilities, and functional skills cannot be overemphasized. It is also vital to understand the various rehabilitation settings available and which setting is most appropriate to allow the older adult to achieve maximal independence in a variety of functional tasks, including driving. PMID- 8504394 TI - Cytogenetic findings in 18 follicular thyroid adenomas. AB - Cytogenetic study of 18 follicular thyroid adenomas showed clonal chromosome changes in 12 tumors. These results suggest the existence of at least three cytogenetically distinct subgroups: a hyperploid group characterized by the presence of a cluster of numerical changes including +5, +7, and +12 as the most frequent anomalies and, less frequently, +4, +9, +14, +16, and +17; a pseudo- or near-diploid group characterized by simple karyotypic aberrations; and a cytogenetically normal group. PMID- 8504395 TI - Gliosis specimens contain clonal cytogenetic abnormalities. AB - The relevance of sex chromosome aneusomy and trisomy 7 in neoplastic brain tissue is controversial. For better understanding of the relative importance of these anomalies, we made a conventional cytogenetic study of cells from tissue obtained from patients who underwent partial cerebral resection for a seizure disorder. Each specimen exhibited "gliosis," but none contained histologically identifiable tumor cells. Sixty-six specimens were analyzed by routine cytogenetic methods. Nonclonal abnormalities were observed in 11.6% of the cells (86% of cases) analyzed. In 11 cases, however, simple clonal karyotypes were observed. Of these cases, six involved loss of a Y chromosome and three involved loss of an X chromosome. Among the cases with loss of an X chromosome, two exhibited multiple abnormal clones. One of these cases had trisomy 7 as well as trisomy 18, and another had a supernumerary psu dic(15)(q13). The supernumerary chromosome was constitutional. One patient had possible Klinefelter syndrome. An additional case had a clonal del(10)(q23) that may have resulted from a hereditary fragile site. We conclude that although some of the apparently acquired clonal and nonclonal abnormalities may be due to a consistent in vitro artifact, it is probable that they are present in the brain tissue itself. Whatever the cause, caution should be used in interpretating cytogenetic abnormalities observed in brain tumor specimens. PMID- 8504396 TI - Incidence of chromosome abnormalities and clinical significance of karyotype in de novo acute myeloid leukemia. AB - Cytogenetic studies with high-resolution banding were performed on specimens from 132 consecutive patients with de novo acute myeloid leukemia (AML). All patients were treated according to therapeutic protocols in the same institution. Clonal abnormalities were detected in 97 of the 124 patients in whom an adequate number of mitoses was obtained (78.2%). Neither sex, FAB classification, WBC, or the extent of bone marrow infiltrate affected the rate of chromosomal aberrations, whereas patients younger than 40 years had a greater proportion of normal karyotypes (p = 0.047). Two different chromosomal classifications were evaluated: the presence of normal and abnormal metaphases (NN-AN-AA classification), and a classification in cytogenetic categories, the latter being based on the frequency of cytogenetic abnormalities. Both classifications were found to correlate significantly with the clinical outcome. They also showed independent prognostic significance when age, sex, and FAB morphology were considered in a multivariate analysis. Two abnormalities were closely associated with specific clinical pathologic subsets of AML. All the 15 patients with t(15;17) had acute promyelocytic leukemia; this translocation was not found in any other subset of AML. Eight of the nine patients presenting rearrangements at 11q23 belonged to a FAB subset with monocytic differentiation (M4 and M5). Our data suggest that cytogenetic findings should influence the therapeutic approach to AML. In particular, young patients with karyotypes associated with poor responses may be considered for more eradicating treatments, including allogenic bone marrow transplantation. PMID- 8504397 TI - Transfected c-Ha-ras oncogene enhances karyotypic instability and integrates predominantly in aberrant chromosomes. AB - A human colon tumor cell line, SW480, was transfected with the c-Ha-ras oncogene, the wild type c-Ha-ras gene, or the pSV2neo plasmid. Cytogenetic analysis and localization of chromosome integration sites were combined in an attempt to analyze the effects of transfection with the c-Ha-ras oncogene on the karyotype. All transfected cell lines showed new clonal chromosome abnormalities present in all cells, ranging from three new aberrations in pSV2neo-transfected SW480 cell lines to eight in c-Ha-ras oncogene-transfected SW480 cell lines. The level of expression of c-Ha-ras mRNA after transfection with the c-Ha-ras oncogene was positively correlated with increased genetic instability, reflected in enhanced karyotypic instability. A combination of banding and fluorescence in situ hybridization (FISH) was used to identify chromosome integration sites. Plasmids containing ras integrated predominantly in new structurally rearranged chromosomes (five of eight). Three of five integration sites in new structurally rearranged chromosomes were localized at or near translocation breakpoints situated in telomeric regions. Specific chromosomes were not involved in the chromosome rearrangements. The results indicate that 1) enhanced expression of c Ha-ras mRNA correlates with an increase in genetic instability in c-Ha-ras oncogene-transfected SW480 cell lines, and 2) that no specific integration site was observed but ras-containing plasmids were located predominantly in aberrant chromosomes near or at translocation breakpoints involving telomeric bands. PMID- 8504398 TI - Chromosomal aberrations in two sporadic gastrinomas. AB - Results of cell culture and cytogenetic analysis (standard and fluorescent in situ hybridization, FISH) of two sporadic gastrinomas are reported. Maintenance of hormonal activity was assessed by detection of gastrin levels during the first 3 months in culture. Case 1 showed clonal aberrations consisting of two marker chromosomes: marker 1 is a large metacentric chromosome and marker 2 is a small acrocentric chromosome. Case 2 showed a constitutional polymorphism with chromosome 15p+ and a clone in the tumor cell culture with trisomy for chromosome 3. To our knowledge, this is the first cytogenetic report of sporadic gastrinomas (Zollinger-Ellison syndrome). PMID- 8504399 TI - Molecular analysis of six variant Philadelphia chromosome translocations in chronic myeloid leukemia. AB - In 420 Philadelphia positive (Ph+) chronic myeloid leukemia (CML) patients karyotyped at diagnosis in our laboratory, 26 Ph variants (6.2%) were observed. Twelve of them are reported. Five cases are "simple" variants without detectable involvement of band 9q34, and seven are "complex," since a third chromosomal band is involved in the Ph formation. Two translocations [t(7;22)(q36;q11) and t(9;22;12)(q34;q11;q11)] are reported for the first time. Six cases were characterized molecularly, and bcr-abl rearrangement was demonstrated, confirming involvement of 9q34 band also in the cases in which chromosomes 9 appear cytogenically normal. Chimeric mRNAs in which M-BCR exon 3 is joined to abl exon 2 (type b3-a2) were detected in four of six cases; one case showed a DNA breakpoint in zone III, which may also give rise to the same transcript. In one case, mRNA junction was b2-a2. The frequency of the b3-a2 junction occurs more frequently in CML patients with a Ph variant than in patients with the standard translocation, suggesting a preferential correlation between this type of transcript and the involvement of other chromosomes in Ph formation. PMID- 8504400 TI - t(8;14)(q11;q32) in acute lymphoid leukemia: description of two cases. AB - An 8;14 chromosome translocation with breakpoints at q11 and q32, respectively, is described as the sole abnormality in bone marrow cells of two adult patients with common acute lymphoblastic leukemia (ALL). The Southern blot analysis revealed a rearrangement after BamHI and HindIII digestion and hybridization with a JH probe, thus demonstrating the involvement of the gene coding for the heavy chains of the immunoglobulins (IgH). Therefore, a pathogenetic mechanism similar to that observed in Burkitt's lymphoma and its variants, or in other lymphomas with t(11;14) or t(14;18), may be hypothesized. In all these cases IgH is juxtaposed to an oncogene (c-MYC, BCL-1, and BCL-2, respectively). A similar structure, with oncogene type potential, could be present on 8q11. The patients underwent a complete remission after induction therapy. PMID- 8504401 TI - Chromosome 7 biclonality in uterine leiomyoma. AB - Biclonal chromosome complements in uterine leiomyoma have been reported occasionally. These previous studies reported the presence of two unrelated clones containing mainly t(12;14) and del(7). We describe four cases of typical leiomyoma displaying two clones, both involving chromosome 7 but with a different deletion in each of the two clones. For two of the tumors, the biclonal origin is the only possible explanation; for the remaining two cases, the origin of the two deleted chromosomes 7 could also be explained by clonal evolution, since the more proximal deletion on chromosome 7 in one clone appears to be subsequent to the deletion of the other clone. Even in these cases, however, the biclonal origin cannot be excluded completely. Despite the mechanism of origin, deletion of chromosome 7 is the most common cytogenetic abnormality in leiomyoma, indicating that loss of genetic material from the long arm of this chromosome is critical for tumor development. PMID- 8504402 TI - Chromosomes 1, 11, and 13 are frequently involved in karyotypic abnormalities in metastatic Merkel cell carcinoma. AB - We report a cytogenetic study of six Merkel cell carcinomas (MCC) in which rearrangement of chromosome 1 was noted in four cases: two cases were trisomic, in one case there was a reciprocal translocation between chromosomes 1 and 5 [t(1;5)(p36;p13)], and in the fourth case all cells had a normal chromosome 1 and three derivatives, a del(1)(p22) and del(1)(q21), and a translocation involving material of unknown origin to the long arm, t(1;?)(q21;?). Four cases demonstrated loss of chromosome 13; in two of these, both copies were lost, and the survival for these two patients was much longer than is common for MCC patients. Partial trisomy of chromosome 11 was noted in two cases, and two patients demonstrated loss of chromosome 22 in all cells examined. Although no consistent chromosome change was noted in our cases, our data and those of previously published reports, show that abnormalities of chromosomes 1, 11, and 13 occur in 30-47% of cytogenetic reports of this rare malignancy. PMID- 8504403 TI - Chromosome analysis of adenomatous polyps of the colon: possible existence of two differently evolving cytogenetic groups. AB - A chromosomal study of 42 colonic adenomatous polyps was performed using a technique of direct chromosome analysis derived from the prenatal procedure for diagnosing chromosomal alterations from chorionic villi sampling. Abnormal karyotypes were found in 22 cases. Trisomy 7, the most frequently found alteration, was found in 13 cases, followed by trisomy 13 (nine cases). Monosomy 18 was observed in two cases; in one of these, that of a polyp which had degenerated into an intra-mucosal adenocarcinoma, it was associated with 17p monosomy. Interestingly, these two types of alterations (trisomy 7 versus 18 and 17p monosomy) were not found together in the same lesion. This suggests that there could be two distinct chromosomal behaviors which might be related to the two cytogenetic groups described for colorectal adenocarcinoma. However, the respective frequencies of such cytogenetic groups varied inversely between adenomas and adenocarcinomas, thus suggesting that they evolve differently. PMID- 8504404 TI - Clinical and cytogenetic significance of myelodysplastic syndromes with disease evolution. AB - We performed a retrospective study of 83 patients with myelodysplastic syndrome (MDS) to clarify the clinical and cytogenetic implications of disease evolution. Twenty-three patients showed disease progression; six of the 11 patients whose disease evolved within 100 days showed complex cytogenetic aberrations and most of them died within 300 days. Of the patients who survived more than 300 days, those with high bone marrow (BM) blast percentages experienced significant disease progression, but we noted no cytogenetic indicators for disease evolution at the later phase. Sixty percent of patients showing karyotypic evolution without disease evolution had deletion-type chromosome changes. The most frequent anomaly in patients with disease evolution who survived more than 300 days was an additional numerical change, whereas patients with disease evolution who survived less than 300 days showed karyotypic instability. It was difficult to predict disease progression for patients whose disease evolved more than 300 days after diagnosis, but in some patients the presence of additional numerical changes was related to disease progression. The cutoff level of early disease evolution was 100 days after diagnosis, and most patients with complex abnormalities survived less than 300 days with or without disease evolution. PMID- 8504405 TI - Cytogenetic findings in a symplastic leiomyoma. PMID- 8504406 TI - Wavelength specific patterns of p53 induction in human skin following exposure to UV radiation. AB - We report that, in human skin, exposure to equally erythemogenic doses of UVA, UVB, and UVC increases immunocytochemically detected p53 in a wavelength-specific pattern. UVC produced immunostaining confined to the upper epidermis. With UVB, staining was seen throughout the epidermis, whereas with UVA staining predominated in the basal layer. The results with UVB and UVC are understandable on the basis of their known differences in penetration, whereas those with UVA are not. This suggests that within one cell type the pattern of p53 response to UV radiation is wavelength dependent. PMID- 8504407 TI - Enhancement of heme oxygenase expression and activity in A431 squamous carcinoma multicellular tumor spheroids. AB - We have investigated the effects of the growth of A431 human squamous carcinoma cells as three-dimensional aggregates (multicellular tumor spheroids) on the expression and enzyme activity of heme oxygenase (HO). We demonstrate that A431 squamous carcinoma cells grown as day 4 spheroids selectively increase the expression of heme oxygenase 1 (HO-1), caused, directly or indirectly, by three dimensional cell-cell contact effects. Steady-state levels of both mRNA and protein are significantly enhanced in spheroids compared with day 4 monolayers (approximately 13-fold). Because of the similarity of apparent half-lives between monolayers (2.7 h) and spheroids (2.1 h), it appears that the increases are caused at least partly by altered transcriptional rates. Total HO enzyme activity, measured by carbon monoxide production, is also up-regulated (2.6-fold) in spheroids, compared to that in monolayers. This increase indicates that the up regulation in HO-1 protein expression corresponds to an increase in functional enzyme levels. We propose that HO may play a more complex role in cellular metabolism than would be evident from studies using two-dimensional monolayer cultures. PMID- 8504408 TI - Increased resistance to oncostatin M-induced growth inhibition of human melanoma cell lines derived from advanced-stage lesions. AB - Human melanomas can become progressively resistant to the growth-inhibitory effects of a broad family of structurally diverse cytokines which includes interleukin 6 (IL-6). Uncovering this multicytokine resistance was made possible by the availability of cell lines established from early-stage radial growth phase or vertical growth phase primary melanomas as well as more advanced primary lesions and distant metastases. Because Oncostatin M (OSM) is also a member of the IL-6 family we evaluated the effects of this cytokine on the growth of human melanoma cell lines obtained from different stages of disease progression. The results showed that three different cell lines derived from early-stage melanomas were strongly growth inhibited by OSM, as they are by IL-6. Three cell lines, established from advanced-stage melanomas, were growth inhibited by OSM, but much higher concentrations (in the range of 10-fold) were required to obtain 50% growth inhibition; these cell lines were not inhibited by IL-6. Three other cell lines that were IL-6 resistant (two of which were advanced stage) were also found to be OSM resistant. Only one advanced-stage IL-6-resistant cell line was found to be highly sensitive to OSM-mediated growth inhibition. In addition, we found that variants isolated from early-stage WM35 melanoma cells that possess a much more aggressive tumorigenic phenotype in nude mice were significantly more resistant to both OSM- and IL-6-mediated growth inhibition. The results demonstrate that OSM can function as a growth inhibitor of human melanoma cells but that its ability to do so is progressively diminished or lost with disease progression. This finding is consistent with the concept of acquired "multicytokine resistance" during melanoma progression. PMID- 8504409 TI - Analysis of WT1 in granulosa cell and other sex cord-stromal tumors. AB - The molecular genetic events involved in the etiology of granulosa cell, Sertoli cell, and Leydig cell tumors are unknown. The expression of the Wilms' tumor suppressor gene WT1 in granulosa and Sertoli cells prompted us to analyze this gene for mutations in 11 granulosa cell tumors, three Leydig cell tumors, and one Sertoli/Leydig cell tumor. Although most of these tumors express WT1 mRNA, none harbors a WT1 mutation in the zinc finger domains where > 90% of WT1 mutations in sporadic Wilms' tumors have been found. In addition we were able to exclude tumor specific loss of heterozygosity in 13 of 15 cases. Taken together these results suggest that the WT1 gene is unlikely to play an important role in the development of sex cord-stromal tumors. PMID- 8504410 TI - Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. AB - In a preceding paper for brain tumors, we demonstrate a tight association between regional hypermethylation at locus D17S5 of chromosome 17p and allelic loss of this chromosome. Because 17p allelic losses occur at the earliest stages of brain tumors, the exact temporal relationship between this event and the hypermethylation could not be elucidated. In renal cancers, two linked structural changes on chromosome 17p, allelic loss and p53 gene mutations, generally occur late in progression. We now show that D17S5 hypermethylation is tightly coupled to both of these genetic changes in late stage renal tumors. However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50%; 17p allelic loss, 13%; p53 mutations, 0%). Our results firmly suggest that D17S5 regional hypermethylation precedes the appearance of the consistent 17p genetic changes in renal cancers, suggesting that this event either marks, or may even cause, chromatin changes which predispose to genetic instability. PMID- 8504411 TI - Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas. AB - The putative tumor suppressor gene DCC has been shown to be frequently lost or expressed at low levels in colorectal, gastric, pancreatic, and esophageal carcinomas. In the present study, the DCC gene and its mRNA expression in human and rat prostatic carcinoma cells as well as in prostatic carcinoma tissues were examined by reverse transcriptase-polymerase chain reaction and polymerase chain reaction-loss of heterozygosity. The DCC gene was present and expressed in normal prostatic cells. However, its expression was decreased or undetectable in all prostatic carcinoma cells from either humans (4 cell lines) or rats (5 cell lines). In patients, 12 of 14 cases (86%) showed reduced DCC expression and 5 of 11 informative cases (45%) showed loss of heterozygosity at the DCC locus. These results demonstrate that loss of DCC expression and loss of heterozygosity at the DCC locus are a frequent feature of prostatic carcinoma cells. PMID- 8504412 TI - Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma. AB - Chromosomal translocations involving band 3q27 and various chromosomal sites, including the sites of the immunoglobulin (Ig) loci (14q32, 2p12, 22q11), represent recurrent aberrations in non-Hodgkin's lymphoma (NHL). In order to identify the putative protooncogene involved in these translocations, we have cloned the breakpoints from two B-cell NHL cases carrying t(3;14)(q27;q32) translocations by screening genomic DNA libraries constructed from NHL biopsy samples with immunoglobulin probes. Several recombinant phages have been obtained from each case and shown to contain sequences from both 14q32 and 3q27 by fluorescence in situ hybridization mapping on metaphase chromosomes. In both cases, the translocation breakpoints were found within the switch region of the Ig heavy-chain locus on 14q32 and within the same 3-kilobase region on 3q27. When used in Southern blot hybridization, a probe from the 3q27 region detected rearrangements in an additional five NHL cases carrying 3q27 translocations with 14q32 or other genomic sites. The same probe detected a predominant 2.4-kilobase mRNA species in several lymphoid cell lines analyzed by Northern blot hybridization. These data suggest that chromosomal breakpoints in 3q27 cluster in the proximity of a transcribed gene which represents a candidate protooncogene (bcl-6) involved in B-cell NHL pathogenesis. PMID- 8504413 TI - Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. AB - The MDM2 (murine double minute 2) gene has recently been shown to code for a cellular protein that can complex the p53 tumor suppressor gene product and inhibit its function. We studied a series of 157 primary brain tumors and report here that the MDM2 gene is amplified and overexpressed in 8-10% of glioblastomas and anaplastic astrocytomas. Thus, MDM2 represents the second most frequently amplified gene after the epidermal growth factor receptor gene in these tumor types. Sequencing of the p53 transcripts in the cases with MDM2 amplification revealed no mutations and restriction fragment length polymorphism analysis showed, with one exception, no losses of alleles on chromosome 17. Our results indicate that amplification and overexpression of MDM2 may be an alternative molecular mechanism by which a subset of human malignant gliomas escapes from p53 regulated growth control. PMID- 8504414 TI - Sensitivity of human cells to mild hyperthermia. AB - The cytotoxic effects of short duration, high temperature, and long duration, low temperature hyperthermia were determined in human cells growing in culture. The human tumor cell lines A549 (lung carcinoma), WiDr (colon carcinoma), and U87MG (glioblastoma) were used. In addition, a normal human lung fibroblast cell type 18Lu was used. Sensitivity to direct cell killing was measured at 41, 43, and 45 degrees C. Heat induced perturbations of cell cycle and proliferation were also analyzed. The results obtained on sensitivity of the above human cell lines at 43 and 45 degrees C are similar to those of the previous work of others in that the human cell lines were observed to be relatively resistant to thermal killing at 43 or 45 degrees C, when compared to heat sensitive rodent cell lines. The comparison is important because most prior hyperthermic research has been performed with rodent cells and clinical protocols have been designed with the use of rodent data. In contrast to the 43 degrees C response, most of the human cells we tested were killed by 41 degrees C heating to an extent greater than that observed for rodent cells. The heat sensitivities of the four different human cell lines varied widely. This appeared to be due to differences in both intrinsic heat sensitivity and tolerance development. During 41 degrees C heating, human cells did not proliferate and cell cycle perturbations developed but did not correlate with sensitivity to killing. Our heat sensitivity measurements point out the shortcomings of using data derived from rodent systems to predict clinical outcome of hyperthermia therapy. PMID- 8504415 TI - Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colon. AB - Epidemiological studies indicate that caloric intake and dietary fat content influence colonic carcinogenesis. In rodents, caloric restriction reduces, and some fats increase, carcinogen-induced colon cancer incidence. The present study was designed to investigate the effects of caloric restriction on colonic cell proliferation (CCP) in carcinogen-treated or control rats fed low- or high-fat diets. F344 rats were treated with azoxymethane (15 mg/kg x2) and then fed an isocaloric AIN 76A diet containing either 5 or 23% corn oil, ad libitum or calorie-restricted to 70 or 80% of the kilocalories consumed by ad libitum rats. Biopsies of the distal colon were taken at 10 and 20 weeks, and rats were sacrificed at 21 or 34 weeks on the experimental diets. Distal CCP was determined by microautoradiography after [3H]thymidine labeling in vitro or presacrifice administration in vivo. The labeling index and number of labeled cells per crypt column were significantly reduced by caloric restriction at all time points (10, 20, 21, 34 weeks). Caloric restriction reduced CCP in high fat- and low fat-fed rats and in azoxymethane-treated and control rats. High fat resulted in decreased CCP in the distal colon compared to low fat at 34 weeks but not earlier. The findings indicate that: (a) caloric restriction is effective in favorably modulating CCP, an intermediate biomarker of colon cancer risk; (b) a high fat ad libitum diet, which increased tumor yield, does not increase distal colon proliferation; (c) dietary fat intake alters proliferation in a manner differing from that induced by changing dietary caloric intake. PMID- 8504416 TI - Increased protein kinase C alpha expression in human colonic Caco-2 cells after insertion of human Ha-ras or polyoma virus middle T oncogenes. AB - The proteins encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancers. To investigate the mechanism(s) whereby oncogenic p21ras and pp60c-src contribute to malignant transformation of intestine, human colonic Caco-2 cells transfected with an activated (Val 12) human Ha-ras gene (Caco-2-T cells) or Py-MT oncogene, a constitutive activator of pp60c-src tyrosine kinase activity (Caco-2-MT cells), were analyzed for tumorigenicity, protein kinase C (PKC) isoform expression, and PKC activity. As compared with control vector Caco-2-H cells, Caco-2-T and Caco-2-MT cells displayed: (a) an enhanced tumorigenicity in nude mice; (b) a 4-fold increase in the level of PKC-alpha mRNA which was not due to enhanced mRNA stability and was mediated through a PKC-independent pathway since it persisted after PKC depletion; (c) increased PKC-alpha immunoreactive protein content (3-fold), total PKC catalytic activity (3.5-fold), and total cell number of [3H]phorbol-12,13 dibutyrate binding sites (4-fold); and (d) a 1.7-fold higher membrane-bound/total PKC activity ratio together with 1.8- and 1.5-fold increases in [3H]arachidonate- and [3H]myristate-labeled diacylglycerol levels. In conclusion, the tumorigenic progression induced by oncogenic p21ras or the Py-MT/pp60c-src complex in Caco-2 cells is associated with increased PKC-alpha gene transcription and PKC-alpha expression as well as with constitutive PKC activation. These results provide the first evidence that the PKC-alpha gene is a target for the signaling pathways of oncogenically activated p21ras and pp60c-src in human colonic cells. They raise the possibility that PKC-alpha is an effector of these oncoproteins for activation of Caco-2 cell tumorigenic potential. PMID- 8504417 TI - Fluorescence postlabeling assay of DNA damage induced by N-methyl-N-nitrosourea. AB - We have used a new technique to assay DNA adduct by combining enzymatic digestion of DNA to nucleotides and fluorescence postlabeling. The assay relies on the selectivity of nucleotide chromatography by high-performance liquid chromatography and the sensitivity of fluorescence detection. This report describes the fluorescence postlabeling assay of N7-(N7-methyldGuo) and O6-methyl 2'-deoxyguanosine (O6-methyldGuo) in calf thymus DNA exposed to N-methyl-N nitrosourea. Using a conventional fluorescence detector, fluorescence postlabeling assay detected 1 modified nucleotide/10(6) normal nucleotides in 100 micrograms DNA. Laser induced fluorescence detection offers a linear response of the chromatographic signal from 10(-13)-10(-16) mol fluorescent nucleotides (correlation coefficient, 0.998) improving the detection limit of the assay to 1 modified nucleotide/10(8) normal nucleotides in 10 micrograms DNA. Fluorescence postlabeling analysis of the authentic markers shows that both N7- and O6 methyldGuo can be assayed with similar detection sensitivity. However, the inherent nature of the instability of N7-methyldGuo, even under physiological conditions, makes its quantitation difficult by any postlabeling technique. O6 MethyldGuo, on the other hand, can be detected with sufficient selectivity and sensitivity by a fluorescence postlabeling assay. Quantitative efficiency of enzymatic excision and chemical postlabeling of O6-methyldGuo were validated by fluorescence postlabeling analysis of synthetic model DNA. Fluorescence postlabeling assay complements 32P-postlabeling assay for O6-methyldGuo without requiring the handling and disposal of radiolabel. Fluorescence postlabeling assay has potential, therefore, to monitor the level of O6-alkyldGuo in human DNA exposed to both environmental and chemotherapeutic alkylating agents. PMID- 8504418 TI - Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats. AB - The modifying effect of dietary protocatechuic acid (PCA) given during the initiation phase or the postinitiation phase on liver carcinogenesis induced by diethylnitrosamine (DEN) was studied in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups and fed the diets containing 500 and 1000 ppm PCA or the basal diet. At 7 weeks of age, all animals except PCA alone and control groups were given DEN at 40 ppm in the drinking water for 5 weeks to induce liver cell neoplasms. Seven days after the DEN exposure, groups of animals fed the PCA diets and continued on these diets until the end of the study. All animals were necropsied during the 37 weeks after the start of the experiment in order to determine the incidences of preneoplastic liver cell foci and neoplasms. Hepatic ornithine decarboxylase activity was also measured in all animals at the termination of the study. Dietary PCA administered at both doses during the initiation phase significantly inhibited the incidence of altered hepatocellular foci resistant for iron accumulation or those positive for glutathione S-transferase placental form and the liver cell tumor incidence and multiplicity. Similarly, the numbers of liver cell foci and neoplasms and tumor multiplicity were significantly reduced in groups fed the PCA diets at the postinitiation stage of carcinogenesis. Hepatic ornithine decarboxylase activity was reduced in DEN-treated animals fed the PCA diets compared to those given DEN alone. Although the precise mechanisms of PCA-induced inhibition of hepatocarcinogenesis remain to be elucidate, it is likely that the inhibitory effects during the initiation and postinitiation phases may be due to alteration in hepatic ornithine decarboxylase activity under the present experimental condition. PMID- 8504419 TI - Pyridyloxobutyl DNA adducts inhibit the repair of O6-methylguanine. AB - The carcinogenic tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), both methylates and pyridyloxobutylates DNA. O6 Methylguanine (O6-mG) persistence has been correlated to NNK-induced lung tumor formation in A/J mice. The pyridyloxobutylation pathway enhances the tumorigenicity of the methylation pathway. In this paper we test the hypothesis that DNA pyridyloxobutylation increases O6-mG persistence by inhibiting the repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Pyridyloxobutylated DNA was generated by reacting calf thymus DNA with the model pyridyloxobutylating agent 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) in the presence of esterase. The alkylated DNA inhibited the ability of partially purified rat liver AGT to repair O6-mG when it was incubated with AGT prior to the addition of 3H-methylated DNA. The extent of inhibition was dependent on the amount of NNKOAc reacted with DNA. The ability of NNKOAc-treated DNA to inhibit AGT was destroyed when the DNA was subjected to neutral thermal hydrolysis. Approximately 1 pmol of AGT was inhibited for every 25 to 50 pmol of 4-hydroxy-1 (3-pyridyl)-1-butanone- releasing adducts present in NNKOAc-treated DNA. The inhibitory activity of this alkylated DNA was relatively stable under physiological conditions (pH 7.4, 37 degrees C). Only 13% of the AGT reactive activity was lost after 7 days. When pyridyloxobutylated DNA was incubated simultaneously with 3H-methylated DNA and AGT, a significant reduction in [3H]methyl transfer to AGT was observed. The levels of reduction were similar to those observed when unlabeled methylated DNA containing comparable levels of O6 mG was substituted for NNKOAc-treated DNA. Based on these results, a cocarcinogenic role for pyridyloxobutylation in NNK-induced lung tumorigenesis is proposed in which pyridyloxobutyl DNA adduct(s) compete with O6-mG for reaction with AGT resulting in sustained levels of O6-mG. These enhanced levels then increase the probability of tumor induction by NNK. PMID- 8504420 TI - Reduction in formation and growth of 1,2-dimethylhydrazine-induced aberrant crypt foci in rat colon by docosahexaenoic acid. AB - The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 times a week for 4, 8, or 12 weeks from the day before the first carcinogen treatment. The numbers of DMH-induced aberrant crypt foci per colon after 4, 8, and 12 weeks of DHA treatment were approximately 40% of those in the respective control groups, and the differences were statistically significant. The numbers of foci reached plateau levels at 8 weeks in both the DHA-treated and control groups. The mean number of aberrant crypts per focus was also significantly smaller in the group given DHA than that in the control group at each time. These results suggest that DHA suppresses the formation and growth of aberrant crypt foci and has a preventive effect on colon carcinogenesis. PMID- 8504421 TI - The significance of DNA damage, its repair and cell proliferation during carcinogen treatment in the initiation of pancreatic cancer in the hamster model. AB - N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) is a complete pancreatic carcinogen in female hamsters at a dose of 210 mg/kg given via an Alzet 2001 pump implanted s.c. Ultimate carcinogenic metabolites of HPOP target DNA to yield 7 and O6-methylguanines (7-mGua, O6-mGua) and 7- and O6-hydroxypropylguanines (7 HpGua, O6-HpGua). During continuous administration of HPOP, levels of DNA alkylation increase linearly with time of exposure and reach a maximum at the end of treatment. Such levels are markedly lower in pancreas or in its component duct or acinar cells than in liver or in other extrahepatic organs examined, indicating that the organotropy of HPOP does not directly correlate to its extent of activation by various tissues. After continuous treatment with HPOP, all major DNA adducts with the exception of 7-mGua in liver are repaired at rates slower than those measured after a single injection of the carcinogen. Half-lives for the repair of O6-mGua are 240 h in liver and considerably longer in extrahepatic tissues. Half-lives for the removal of 7-mGua are 46, 55, 72, and 96 h in liver, kidney, lung, and pancreas; while respective values for 7-HpGua are 216, 216, 132, and 140 h. No significant repair is observed for O6-HpGua for at least 8 days. The above differences in half-lives result in the gradual increase of 7 HpGua and O6-HpGua relative to their methyl counterparts. DNA synthesis progressively increases during HPOP infusion in all the tissues examined, and reaches maximum levels 3 to 4 days after termination of treatment. In pancreas, such levels are up to 5 times greater in HPOP treated animals than in controls. The increase in DNA synthesis during carcinogen treatment is due to the greater number of cells entering S phase rather than to an increase in the rate of proliferation of a certain population of cells. The mitogenic effect of HPOP in the pancreas and the persistence of highly promutagenic hydroxypropyl adducts are postulated to contribute to the initiation of pancreatic cancer in the hamster model. PMID- 8504422 TI - Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes). AB - A liposome-encapsulated form of doxorubicin (TLC D-99), which was shown in preclinical toxicology to be less toxic to the gastrointestinal tract and myocardium than free doxorubicin, was administered by constant infusion (1.00 1.80 h) to 38 patients in single doses of 20, 30, 45, 60, 75, and 90 mg/m2 every 3 weeks and daily for 3 days at doses of 20, 25, and 30 mg/m2/day. The dose limiting toxicity was leucopenia: the maximum tolerated doses were one at 90 mg/m2 and three at 25 mg/m2/day. Nausea, vomiting, and stomatitis were minimal or absent at each dose; alopecia was minor. Fever and chills were noted at most of the doses, and malaise was seen in some patients, especially at the higher doses. No hepatic, renal, or other organ toxicities were observed. Clinical cardiac toxicity was not observed in any patient; however, the cumulative doxorubicin dose was greater than 400 mg/m2 in only one patient. There was large variation among patients in estimated pharmacokinetic parameters and profiles. Higher plasma levels and dose intensities were achieved with TLC D-99 than were predicted for free doxorubicin. Liposome-encapsulated doxorubicin was well tolerated and produced less nausea, vomiting, and stomatitis than would be expected with free doxorubicin administered at equally myelosuppressive doses. PMID- 8504423 TI - In vivo administration of the anticancer agent bryostatin 1 activates platelets and neutrophils and modulates protein kinase C activity. AB - Bryostatin 1 is a naturally occurring macrocyclic lactone which when applied to cells in culture activates protein kinase C (PKC). In vivo bryostatin 1 functions as an anticancer agent with activity against murine lymphomas, leukemias, and melanoma. Because all organs and tissues contain PKC, normal cells would also be a likely target for this agent. Here we demonstrate that in vivo administration of bryostatin 1 activates platelets over a dose range of 0.4 to 40 micrograms/kg with half-maximal activation occurring at 3 micrograms/kg and stimulation of neutrophils over a similar dose range. This in vivo activation of neutrophils is associated with a rapid decrease in measurable cytosolic PKC, a finding consistent with translocation of the enzyme to the membrane. In contrast, no statistically significant change in PKC location was found in liver, spleen, brain, or L10A B-cell lymphoma. However, in culture the L10A lymphoma did respond to bryostatin 1 with translocation of PKC. To evaluate whether the lack of effect of bryostatin 1 on PKC in organs was secondary to rapid degradation, we developed a bioassay to measure the levels of bryostatin 1 in the blood. To measure the presence of bryostatin 1, human neutrophils were incubated with plasma from mice given injections of different concentrations of bryostatin 1. Using this assay, bryostatin 1 at levels as low as 60 nM could be measured in the plasma. A time course with this bioassay demonstrated that less than 10% of the bryostatin 1 injected was detectable after 2.5 min. These results demonstrate that bryostatin 1 is capable of activating platelets and neutrophils and modulating PKC in vivo. The lack of effect of bryostatin 1 on specific organs may be secondary to the rapid clearance/degradation of this compound from the blood. PMID- 8504424 TI - Relationship between circadian-dependent toxicity of 5-fluorodeoxyuridine and circadian rhythms of pyrimidine enzymes: possible relevance to fluoropyrimidine chemotherapy. AB - Previous studies in experimental animals and patients have suggested a circadian variation in host toxicity following administration of 5-fluorodeoxyuridine (FdUrd) although the biochemical mechanisms are not fully understood. Thymidine kinase (TK; EC 2.7.1.21), the initial enzyme in the thymidine-phosphorylation pathway, is the first enzyme in the anabolism of FdUrd. Dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), is the rate-limiting enzyme in the pyrimidine catabolic pathway and has been shown to be the key enzyme in FdUrd catabolism. The present study examined the relationship between the suggested circadian variation in FdUrd toxicity and potential circadian variations in the activity of these enzymes. Initial studies in Sprague-Dawley rats confirmed that the time of FdUrd administration affected death rate and other drug-related toxicities including loss of body weight, diarrhea, and bone marrow suppression, with the least toxicity and highest survival rate being observed in rats receiving FdUrd at 12:00 noon and 4:00 p.m. and the greatest toxicity and lowest survival rate at 12:00 midnight and 4:00 a.m. Statistical analysis revealed a circadian pattern in FdUrd toxicity (Cosinor analysis, P < 0.001). In subsequent studies with the same species, we simultaneously measured TK and DPD activities in several tissues at various times over 24 h. Under standardized light conditions (lights on, 6:00 a.m. to 6:00 p.m.; lights off, 6:00 p.m. to 6:00 a.m.), with sampling at 4-h intervals (4:00 and 8:00 a.m.; 12:00 noon; 4:00 and 8:00 p.m., and 12:00 midnight), a circadian variation in TK activity was observed (P < 0.0001, Cosinor analysis) in bone marrow, intestinal mucosa, liver, and spleen. In the same group of animals, a circadian pattern of DPD activity in liver and bone marrow was also observed (Cosinor analysis, P < 0.0001) that was inverse compared to the circadian variation in TK activity (Pearson correlation analysis, P < 0.05). Further statistical analysis indicated that the observed circadian variation in FdUrd toxicity was correlated with the circadian variation of TK activity and inversely correlated with DPD activity (Pearson correlation analysis, P < 0.05). Based on the above data, we conclude that the circadian pattern of TK and DPD activity may explain the observed circadian variation in toxicity as the time of FdUrd administration is varied. These results may be useful in the design of improved chemotherapeutic regimens using time-modified administration of FdUrd. PMID- 8504425 TI - Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1 piperidino]-1-piperidino)-carbonyloxy-camptothecin against human tumor xenografts: lack of cross-resistance in vivo in tumors with acquired resistance to the topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin. AB - The efficacy of the topoisomerase I inhibitor CPT-11 [7-ethyl-10-(4-[1 piperidino]-1-piperidino)-carbonyloxycamptothec in] has been evaluated against a panel of human tumor xenografts derived from adult and pediatric malignancies. Tumors included eight colon adenocarcinomas representing intrinsically chemorefractory malignancies, six lines derived from childhood rhabdomyosarcoma (three embryonal and three alveolar) representing a chemoresponsive histiotype, and sublines of rhabdomyosarcomas selected in vivo for resistance to vincristine, melphalan, and the topoisomerase I inhibitor 9-dimethylaminomethyl-10 hydroxycamptothecin (topotecan). CPT-11 was given by i.v. administration daily for 5 days each week for 2 weeks (one cycle of therapy) or on the same schedule with cycles repeated every 21 days. The maximum tolerated dose for a single cycle of treatment was 40 mg/kg/dose, and for 3 cycles the maximum tolerated dose was 10 mg/kg/dose. Treatment was started against advanced tumors. Against colon adenocarcinomas CPT-11 administered for one cycle at the maximum tolerated dose caused complete or partial regression (> or = 50% reduction in tumor volume) in 5 of 8 lines. One cycle of CPT-11 therapy caused significant inhibition of tumor growth, without 50% regression, in 2 of 3 other colon adenocarcinomas. Rhabdomyosarcoma xenografts derived from untreated patients were highly responsive to CPT-11, which caused complete regression in 5 of 6 lines even at 20 or 10 mg/kg/dose. CPT-11 retained complete activity against rhabdomyosarcomas selected for resistance to vincristine and caused complete regressions in a line selected for resistance to melphalan that was also completely cross-resistant to topotecan. Of note was the observation that CPT-11 was as active against two xenografts selected for primary resistance to topotecan as it was against the respective parental tumors. Preliminary data indicate that CPT-11, like the topoisomerase I inhibitor topotecan, may have increased therapeutic efficacy when administered at a low dose for protracted periods (3 cycles). A comparison of the efficacy of CPT-11 with topotecan is presented. PMID- 8504427 TI - Preclinical evaluation of 111In-labeled B3 monoclonal antibody: biodistribution and imaging studies in nude mice bearing human epidermoid carcinoma xenografts. AB - Biodistribution and imaging characteristics of monoclonal antibody B3 were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. B3 is a murine IgG1k, recently isolated, reacting with a carbohydrate epitope abundantly and uniformly expressed by most carcinomas. B3 was conjugated to a new backbone-substituted derivative of diethylenetriaminepentaacetic acid, 2-(p isothiocyanato benzyl)-cyclohexyl-diethylenetriaminepentaacetic acid, and labeled with 111In. Tumor-bearing mice were given i.v. injections of approximately 5 microCi of either 111In-B3 or 111In-MOPC-21, an isotype-matched control, and sacrificed in groups of five at 6 h and daily up to 168 h. Imaging was performed at 24, 72, and 144 h. Significant differences were observed in tumor uptake at all time points with peak values at 48 h (25 +/- 5.2% versus 6.3 +/- 0.4% of the injected dose/g tissue) (mean +/- SD) for 111In-B3 and 111In-MOPC-21, respectively (P < 0.001). All tumor to organ ratios increased with time for 111In B3. In particular, tumor:liver ratios rose from 3.2 +/- 0.6 at 24 h to 6.3 +/- 1.2 at 168 h. Imaging results showed selective and progressive accumulation of 111In-B3 at the tumor site, whereas 111In-MOPC-21 did not show specific localization. In summary, 111In-labeled B3 demonstrated good and specific tumor targeting, which warrants its future clinical evaluation. PMID- 8504426 TI - Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis. AB - In a recent study we detected marked differences in the antigenic profile of acral lentiginous melanoma (ALM) and nodular melanoma lesions. Furthermore, we showed that the human high molecular weight melanoma-associated antigen (HMW-MAA) is expressed with a significantly higher frequency in metastatic than in primary ALM lesions. Because of the potential role of HMW-MAA in the metastatic process of melanoma cells, in the present investigation we tested whether HMW-MAA represents a useful prognostic marker in ALM. Primary ALM lesions removed from 32 patients were stained with anti-HMW-MAA monoclonal antibody (mAb) in an immunoperoxidase reaction. The results were correlated with the expression of other markers defined by mAb, with clinical parameters of the disease, and with histopathological characteristics of the lesions. Only 9 of the 32 primary ALM lesions tested were stained by anti-HMW-MAA mAb. Expression of HMW-MAA was the only variable associated with patients' survival and disease-free survival. Both were significantly shorter in patients with HMW-MAA expression in their primary lesions. These results suggest that HMW-MAA may represent a novel prognostic marker in ALM, since phenotyping of primary ALM lesions with anti-HMW-MAA mAb may provide information about the prognosis of the disease which cannot be obtained with known prognostic parameters. PMID- 8504428 TI - Mutagenicity and mutational spectrum of N-methyl-N'-nitro-N-nitrosoguanidine in the hprt gene in G1-S and late S phase of diploid human fibroblasts. AB - To investigate the effect of DNA replication on the mutation spectrum induced in diploid human fibroblasts by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cells were synchronized and exposed to MNNG either at the G1-S border or in late S phase, and the mutations in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene were examined. The coding regions of 92 independent mutants were characterized by direct sequencing of mRNA-polymerase chain reaction-amplified complementary DNA. While there was little difference in the sensitivity of the two populations to the cytotoxic effects of MNNG, the frequency of mutants induced in late S populations was significantly lower than that induced in G1-S populations. The majority of induced complementary DNA mutations were single base substitutions (54%) and splice site mutations (43%). Analysis of the intron-exon boundaries of more than one-half of the splicing mutants showed that almost all contained base substitutions in the hprt gene. A broad mutational spectrum was observed in low-dose (4, 6, or 8 microM) treatments; only 27% were G to A transitions, whereas 80% of base substitutions derived from the high-dose (10 or 12 microM) treatments were G to A transitions in G1-S populations. An intermediate frequency (64%) of G to A transitions was observed in late S populations exposed to MNNG. When the causative premutation lesion was O6 methylguanine, 75% of G to A transitions that were observed in G1-S populations clustered on both the transcribed and the nontranscribed strands of the 5' half of the hprt gene. In contrast, 50% of G to A transitions were located only on the nontranscribed strand of this region in late S populations. The results indicate that O(6)-alkylguanine-DNA-alkyltransferase may not efficiently remove O(6) methylguanine from the 5' half of the gene but can repair lesions far away from this region during initiation of replication. Our results are consistent with the notion that the putative origin of replication is located at intron 1 of the hprt gene. PMID- 8504429 TI - Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. AB - Head and neck cancer development has been proposed to represent a multistage process characterized by dysregulation of proliferation and differentiation and driven by an accumulation of genetic alterations in an anatomic field repeatedly exposed to carcinogens. To visualize the accumulation of genetic alterations during head and neck tumorigeneses and to determine the extent of the genetically altered field, we probed 25 squamous cell carcinomas of the head and neck and their adjacent premalignant lesions for numerical chromosome aberrations by nonisotopic, in situ hybridization using chromosome-specific centromeric DNA probes for chromosomes 7 and 17. Normal control oral epithelium from individuals free of cancer showed no chromosome polysomy (i.e., cells with > or = 3 chromosome copies), whereas histologically normal epithelium adjacent to the tumors showed squamous cells with polysomies for chromosomes 7 and 17. Moreover, the frequency of cells with polysomy increased as the tissues passed from histologically normal epithelium to hyperplasia to dysplasia to cancer. The finding of genotypic abnormalities in histologically normal and precancerous regions adjacent to the tumor supports the concept of field cancerization. The finding of progressive genetic changes as the tumor develops supports the concept of multistep carcinogenesis in the head and neck region. Such genotypic parameters could serve as biomarkers in the assessment of the risk of progression to malignancy and as intermediate end points in chemoprevention trials. PMID- 8504430 TI - Codons 12 and 13 of H-ras protooncogene interrupt the progression of DNA synthesis catalyzed by DNA polymerase alpha. AB - Mutagenesis of protooncogenes has been postulated to contribute to the initiation and progression of human cancer. Activating mutations in the H-ras gene are predominantly single-base substitutions and are most frequently identified at codons 12, 13, and 61. We have analyzed the effects of DNA sequence context at specific codons that are hot spots for ras mutation with respect to abnormalities in copying by purified DNA polymerase alpha, a major eucaryotic replication enzyme. Exon 1 of H-ras gene was inserted into M13 mp19, single-stranded DNA constructs were isolated, and the progression of synthesis by polymerase alpha was measured. Strong termination sites were found in codons 12 and 13. Pausing at these codons is abolished when the template is mutated at the middle base of codon 12, the same alteration that converts H-ras into an activated oncogene. Resistance of codon 12 in double-stranded constructs to digestion with restriction enzymes and computer investigation of the ras sequence suggest that these termination sites are in a region of secondary structure. The frequency of sequence alterations within DNA chains that have been extended past codons 12 and 13 was found to be < 0.01. We consider a variety of mechanisms by which the potential secondary structure involving codons 12 and 13 may contribute to the pausing of DNA polymerase alpha and to the generation of clustered mutations at this site. PMID- 8504431 TI - Isoglobotetraosylceramide is a marker for highly metastatic cells in rat mammary adenocarcinomas. AB - We have previously identified a neutral glycolipid antigen which appears to be a surface antigenic marker for the metastatic subpopulation in the R3230AC rat mammary adenocarcinoma (S.A. Carlsen, M. Barry, and K. Newton, Clin. Exp. Metastasis, 8: 141-151, 1990). In this article we describe the structural characterization of this glycolipid antigen. The sequence of the sugars in the saccharide portion of the molecule was determined by specific glycosidase cleavage and further confirmed by mass spectroscopic analysis. The nature of the linkages between the monosaccharide units was determined by methylation analysis. The final structure was confirmed by NMR analysis and found to be isoglobotetraosylceramide (GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Gle beta 1-O ceramide). We also present evidence that the cells marked by this antigen have a higher metastatic potential than the cells lacking this glycolipid as measured by the formation of lung colonies after i.v. injection of the cells into the tail vein of the rat. Furthermore, isoglobotetraosylceramide seems to play a direct role in the metastatic process since the blocking of exposed antigen with monoclonal antibodies, or their Fab fragments, results in a highly significant decrease in lung colony formation. PMID- 8504432 TI - Vascular permeability factor (vascular endothelial growth factor) in guinea pig and human tumor and inflammatory effusions. AB - Vascular permeability factor (VPF), also known as vascular endothelial growth factor, is a dimeric M(r) 34,000-42,000 glycoprotein that possesses potent vascular permeability-enhancing and endothelial cell-specific mitogenic activities. It is synthesized by many rodent and human tumor cells and also by some normal cells. Recently we developed a sensitive and specific time-resolved immunofluorometric assay for quantifying VPF in biological fluids. We here report findings with this assay in guinea pigs and patients with both malignant and nonmalignant effusions. Line 1 and line 10 tumor cells were injected into the peritoneal cavities of syngeneic strain 2 guinea pigs, and ascitic fluid, plasma, and urine were collected at various intervals. Within 2 to 4 days, we observed a time-dependent, parallel increase in VPF, ascitic fluid volume, and tumor cell numbers in animals bearing either tumor line; in contrast, VPF was not detected in plasma or urine, even in animals with extensive tumor burdens. However, low levels of VPF were detected in the inflammatory ascites induced by i.p. oil injection. In human studies, high levels of VPF (> 10 pM) were measured in 21 of 32 effusions with cytology-documented malignant cells and in only seven of 35 effusions without cytological evidence of malignancy. Thus, VPF levels in human effusions provided a diagnostic test for malignancy with a sensitivity of 66% and a specificity of 80% (perhaps as high as 97% in that six of the seven cytology negative patients with VPF levels > 10 pM had cancer as determined by other criteria). As in the animal tumor models, VPF was not detected in serum or urine obtained from patients with or without malignant ascites. Many nonmalignant effusions contained measurable VPF but, on average, in significantly smaller amounts than were found in malignant effusions. VPF levels in such fluids correlated strongly (p = 0.59, P < 0.001) with monocyte and macrophage content. Taken together, these data relate ascitic fluid accumulation to VPF concentration in a well-defined animal tumor system and demonstrate, for the first time, the presence of VPF in human malignant effusions. It is likely that VPF expression by tumor and mononuclear cells contributes to the plasma exudation and fluid accumulation associated with malignant and certain inflammatory effusions. The VPF assay may prove useful for cancer diagnosis as a supplement to cytology, especially in tumors that grow in the pleural lining but not as a suspension in the effusions that they induce. PMID- 8504433 TI - Expression of the gastrin gene in the normal human colon and colorectal adenocarcinoma. AB - Gastrin, produced in the G-cells of the gastric antrum and regulating acid secretion in the stomach, also acts as a trophic factor in the gastrointestinal tract. Because of its possible role in colon cell proliferation and differentiation, evidence for its presence in normal colorectal mucosa and adenocarcinoma was sought. Utilizing tumors and matched normal mucosa from 26 patients, mature gastrin and progastrin were studied by immunohistochemistry. In normal colonic mucosal crypts, occasional cells stained concordantly for gastrin, progastrin, and chromogranin A, suggesting that they are of neuroendocrine origin. Adenomatous polyps stained neither for gastrin nor chromogranin A. In 22 of 23 adenocarcinomas, more than 50% of tumor cells stained for gastrin and progastrin. The expected gastrin transcript was demonstrable by polymerase chain reaction and RNase protection in tumors and by polymerase chain reaction in normal mucosa. Its identity was confirmed by sequencing the polymerase chain reaction product. A larger transcript containing Intron II was present in both cancers and normal mucosa but was barely discernible in the gastric antrum. Aberrant expression of gastrin may contribute to deregulated proliferation of many colorectal carcinomas. PMID- 8504434 TI - Successive activation of the platelet-derived growth factor beta receptor and platelet-derived growth factor B genes correlates with the genesis of human choriocarcinoma. AB - The hydatidiform mole is a benign disease of the placenta characterized by the absence of the maternal genome. Approximately 3% of the reported cases will develop into malignant choriocarcinoma. In situ hybridization analysis reveals that the paternal platelet-derived growth factor (PDGF) beta receptor gene is up to 2 orders of magnitude more active in cytotrophoblasts of the complete hydatidiform moles than in normal placentae. The transition between hyperplasia (complete hydatidiform mole) and neoplasia (choriocarcinoma) in these cells correlates with at least a 10- to 20-fold activation of the PDGF-B gene. Since the neoplastic cytotrophoblasts have maintained an abnormally high level of PDGF beta receptor expression, we propose that a deregulated PDGF autostimulatory loop is involved in the genesis of human choriocarcinoma from hydatidiform moles. PMID- 8504435 TI - Thrombolytic therapy for acute ischemic stroke. AB - Emergency treatment of acute thromboembolic stroke by lysis of the occlusive arterial clot has received increasing attention in recent years. Development of newer thrombolytic agents combined with an enhanced appreciation of the time course of reversible cerebral ischemia have led to further clinical and laboratory exploration of this approach to stroke treatment, which had previously been believed to be unsafe. Recent studies suggest that very early recanalization of cerebral arteries can be achieved with acceptable risks using either local arterial or intravenously administered thrombolytic agents. While most published reports have suggested clinical benefit, definitive proof of sustained clinical efficacy, as measured by overall functional outcome and compared to concurrent controls, remains to be established. PMID- 8504436 TI - 4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety. AB - In a recent randomized, double-blind, placebo-controlled crossover trial, we demonstrated efficacy of 4-aminopyridine (4-AP) in improving disability of patients with multiple sclerosis (MS). Here we describe the relationship between dosage, serum level, efficacy, and safety of intravenously and orally administered 4-AP in the same group of 70 MS patients. After both intravenous and oral administration there was a significant relationship between serum levels and 4-AP doses used (p < 0.001 and p < 0.01, respectively). The use of 4-AP in oral doses three times a day showed a large variation and fluctuation in serum levels. After 12 weeks of oral treatment (maximum daily dosage 0.5 mg/kg body weight), a statistically significant improvement was found for the smooth pursuit gain of the eye movements (estimated effect 0.14, 95% confidence interval 0.06-0.23, p < 0.001). The amount of improvement was significantly related to 4-AP serum levels (p = 0.0013). Side effects after intravenous 4-AP occurred frequently and were very troublesome (pain in infusion arm, dizziness). Side effects during oral treatment (dizziness, paresthesias) were very mild and occurred 30-45 min after intake of the medication and could be related to high serum levels. PMID- 8504437 TI - Quantitative electromyographic analysis of changes in muscle activity following botulinum toxin therapy for cervical dystonia. AB - Reports of efficacy of botulinum toxin for cervical dystonia have relied on subjective reports of improvement or various clinical rating scales. We studied 19 patients with cervical dystonia using Turns analysis to determine if quantitative EMG measures of muscle activity changed following botulinum toxin injections. Before and after botulinum toxin injections, six muscles were evaluated bilaterally. Quantitative EMG analysis of active muscles injected with botulinum toxin showed a significant decline in muscle activity after botulinum toxin (F = [1,41] 55.0; p < 0.001). Significant reductions in quantitative EMG parameters were also noted in noninjected active muscles after botulinum toxin treatment (F = [1,51] 59.15; p < 0.001). The sum of EMG activity for all active muscles was calculated for each subject and showed a significant reduction after botulinum toxin injection [MANOVA: (F = [1,5] 5.69; p < 0.05]. Quantitative EMG assessment provides an objective measure of response to botulinum toxin. Decreased muscle activity in noninjected muscles may result from toxin diffusion or reflect relaxation of muscles only secondarily involved in cervical dystonia. PMID- 8504438 TI - Influence of carbamazepine on Li+ ratio in healthy volunteers: an in vitro method. AB - Thirty-six healthy volunteers, 19 men and 17 women, were selected to study the possible influence of carbamazepine on Li+ ratio in vitro. The study used within Ss design. The procedure for preparing and calculating Li+ ratio in vitro followed Pandey's method. Twenty milliliters of blood was withdrawn from each subject, and divided evenly into three test tubes containing sodium heparin. Test tube 1 (control) went through the regular Pandey's method; test tube 2 went through the same procedure, except both the loading and incubation media contained 35 mu mol/L of carbamazepine. The result showed that carbamazepine did not significantly alter Li+ ratio in vitro. The neurotoxicity resulting from lithium-carbamazepine combination might be related to carbamazepine alone or preexisting physical conditions or interactions not related to Li+ ratio. PMID- 8504439 TI - Differentiation between MK-801- and apomorphine-induced stereotyped behaviors in mice. AB - The ability of phencyclidine (PCP) to model schizophreniform psychosis is believed to be related to its ability to produce both hypoglutamatergia and hyperdopaminergia. As such, identification of PCP-stimulated behaviors may be important for the development of animal models of schizophrenia. In this study, MK-801 [(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cycloheptane-5,10-imine maleate], a high-affinity PCP analogue, was administered to mice in order to stimulate "PCP behaviors." These PCP behaviors were compared with behaviors stimulated by apomorphine, a dopamine agonist. Stereotyped behavior was assessed by both visual observations and automated measurements. Visual observations showed highly intense gnawing and sniffing in apomorphine-treated mice and the absence of gnawing in MK-801-treated mice. Automated stereotypic measures showed that, compared with vehicle-treated controls, there were frequent dissociations between MK-801 and apomorphine. Conceivably, a compound that attenuates PCP stimulated behaviors while sparing apomorphine-stimulated behaviors would possess both antipsychotic efficacy and be devoid of undesirable side effects associated with dopamine blockade. PMID- 8504440 TI - Cytokine production in anorexia nervosa. AB - The capacity of peripheral blood mononuclear cells (PBMCs) of anorexia nervosa (AN) patients to produce interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-3-like activity (IL-3-LA) was studied. A significantly lower (-49%, p < 0.005) capacity to synthesize IL-2 and an almost significantly impaired ability (-35%, p = 0.058) to release IL-3-LA by PBMCs of AN patients was found, as compared with cells of the control group. IL-1 production, either spontaneous or after stimulation with lipopolysaccharide (LPS), did not differ significantly between AN patients and healthy subjects. The lessened capacity to produce IL-2 was accompanied by an enhanced stimulatory activity of the patient sera on the production of this cytokine by PBMCs of healthy subjects. It is therefore suggested that the serum of AN patients contains a stimulatory factor or factors for cytokine production that compensates for the lower production of cytokines by AN PBMCs. Such a compensatory mechanism may explain why AN patients do not have an higher susceptibility to infections. PMID- 8504441 TI - Worsening of postural tremor in patients with levodopa-induced dyskinesia: a quantitative analysis. AB - Some investigators have proposed that Parkinson's disease (PD) patients often exhibit a worsening of tremor before the emergence of levodopa-induced dyskinesia (LDD). It is not clear, however, whether the presence of tremor depends on the severity of dyskinesia, nor is the precise time course of tremor relative to dyskinesia well understood. This report describes an objective study of the relationship between postural tremor and dyskinesia in eight PD patients who showed signs of choreoathetoid hand movements after a single dose of levodopa. Spectral analysis of sustained hand force provided an objective and sensitive method of detecting worsening of tremor in patients with LDD. Severity of clinical symptoms was highly correlated with severity of dyskinesia. Six of the patients exhibited increased tremor amplitude within 45 min of exposure to levodopa, with two of the six patients experiencing bilateral and four of the six having unilateral worsening of postural tremor. Tremor was more severe on the side with the more severe dyskinesia. These findings provide objective support for the notion that dyskinesia and postural tremor may stem from a common pathophysiologic mechanism. PMID- 8504442 TI - Measurement of an explosive behavior in the mouse, induced by MK-801, a PCP analogue. AB - MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor complex that binds with high-affinity to the phencyclidine (PCP) binding site, stimulated an outbred strain of NIH Swiss mice to display discrete episodes of explosive jumping behavior, designated as "popping." The episodes of this behavior were characterized with respect to their dose dependency, latency, and duration. The number of mice displaying this behavior increased with increasing doses of MK-801. The intensity of the popping behavior was sensitive to dose dependent inhibition by haloperidol, a conventional antipsychotic medication, and clozapine, an atypical antipsychotic medication. In view of PCP's ability to precipitate a schizophreniform psychosis in humans, the behavior may serve as a useful preclinical paradigm for the screening of potentially novel antipsychotic medications. PMID- 8504443 TI - Encephalopathy, myelopathy, optic neuropathy, and anosmia associated with intravenous cytosine arabinoside. AB - Coma, hemiparesis, unilateral optic neuropathy, and anosmia manifested in a patient with leukemia after he received only three courses of intravenous high dose cytosine arabinoside (ARA-C). The patient's mental status returned to normal after several days, and his hemiparesis resolved. However, the visual loss persisted, and near complete visual loss in the other eye ensued over the following month. Severe bilateral optic atrophy appeared as the visual loss progressed. Anosmia became evident after resolution of the coma and did not improve. The patient had previously had a thoracic myelopathy 2 weeks after receiving low-dose i.v. ARA-C. The neurotoxicity of high-dose i.v. ARA-C may arise at much lower cumulative doses than has been reported. In addition to cerebellar dysfunction and somnolence, high-dose i.v. ARA-C may produce optic neuropathy, anosmia, and hemiparesis. PMID- 8504444 TI - Parkinsonism unmasked by verapamil. AB - We report the case of a 55-year-old man who had a parkinsonian syndrome unresponsive to levodopa for 5 years and had been taking verapamil during the past 8 years. Parkinsonian signs improved markedly after withdrawal of verapamil, suggesting its role in unmasking the parkinsonism. To our knowledge, this side effect of verapamil has not been described previously. PMID- 8504445 TI - Alopecia: an adverse effect of bromocriptine. AB - We report the cases of two patients who experienced a poorly known adverse effect of bromocriptine-alopecia. The first patient was an infertile 34-year-old woman treated with 2.5 mg of bromocriptine per day. The second patient was a 45-year old woman with Parkinson's disease treated with 40 mg of bromocriptine per day. In both cases there was no preexisting hair loss. Hair loss ceased when bromocriptine was withdrawn and was not attributed to another etiology. Pathophysiological mechanisms are unknown. PMID- 8504446 TI - [The epidemiology of coronary heart disease (CHD) in 16 provinces of China. Multi province Cooperative Group of Cardiovascular Disease Surveillance (MONICA Project)]. AB - This paper presents the cross-section results of epidemiological survey for acute CHD event in sixteen provinces of China, using the data of Multi-province Cooperative Surveillance Study on Cardiovascular Disease (MONICA Project), 1987 1989. The results showed that there were significant differences in geographical distribution of the morbidity and of the mortality of CHD event. The northern provinces had higher rates than southern provinces. There was a positive correlation between the morbidity of CHD and the geographical altitudes. The coefficients of correlation were 0.5 and 0.57 for male and female, respectively (P < 0.05). Male had higher morbidity and mortality than female. The average sex ratio (male/female) for the morbidity was 2.20. There were higher rates in urban areas as compared with those in rural areas. There were higher case fatality rates in most provinces. The average percentage for the death out-of-hospital was 43.91% of the total number of CHD death. The percentage of death within 1 hour after onset accounted for 35.13% of the total number of CHD death. The duration from onset to death was less than 24 hours in 72.96% of the total number of CHD death. The results are of important values for the prevention, treatment and the etiologic study of CHD. PMID- 8504447 TI - [A population-based case control study of primary liver cancer in Fusui]. AB - A population-based case control study of primary liver cancer (PLC) was undertaken in Fusui County, Guangxi Autonomous Region. Ninety-nine PLC cases and 99 age-sex-matched controls were surveyed for their general conditions, life style features, dietary habits, types of drinking water and family history. Cases and controls were well distributed in nationality, education, marital status and annual income per person. Conditional logistic regression results showed that HBV infection, drinking pond-ditch water, family history and total alcohol intake were the risk factors of PLC with the relative risks 5.330 (2.502-11.35), 3.703 (1.251-10.96), 2.881 (1.289-6.441), 1.002 (1.000-1.004), respectively. And antibody of HBV surface antigen is protective factor with the relative risk of 0.418 (0.210-0.834). PMID- 8504448 TI - [Sino-MONICA project: comparison of risk factors of cardiovascular diseases in 13 provinces or cities and the trend of their changes]. AB - This paper shows the results of the base-line and middle population surveys in 1984-86 and 1988-89 in 15 collaborative centers in 13 provinces. Use of standardized methods allows us to make cross-sectional comparisons and trend evaluations. The prevalence rates of actual hypertension and median BMI values in the north are much higher than those in the south. The risk of cardiovascular disease increased in most provinces between the two surveys carried out in 1984 85 and 1988-89, especially in hypertension prevalence rate and body mass index. PMID- 8504449 TI - [Investigation on insomnia and use of hypnotics among an adult population]. AB - An epidemiological enquiry about the sleep status and use of hypnotics in 1289 adults (742 men and 547 women), including 266 workers, 195 peasants, 275 intellectuals and 553 college students, was done in 1989. A questionnaire including 15 questions on sleep habits, sleep disorders and consumption of hypnotics was used. The response percentages were compared with chi-square test between different sexes, age groups, professions and places of residence. 52.9% and 5.4% of the sample complained of transient and persistent insomnia, respectively. Our data did not reveal sex difference as insomnia is concerned. The response percentages for transient insomnia did not correlate with age, while persistent insomnia definitely increased from middle age. Both transient and persistent insomnia were present much less in rural residents than in towns folks. No significant difference in the incidence of insomnia was found between intellectuals and workers. Only 1.1% of the sample used hypnotics regularly and 10.9% had ever taken sleeping pills. PMID- 8504450 TI - [The type of leptospirosis epidemic and serogroup transformation in Fujian province in recent years]. AB - By analysis of investigations in recent years in Fujian province, it was found that the main type of leptospirosis epidemic was rice-field type, the other was flood type which had the tendency to shift from coastal plain area to northwest area. In the main epidemic area, Wupin county, the detection rate of Hebdomadis serogroup rate sharply declined (P < 0.01), however, that of Batavia serogroup markedly increased (P < 0.01). PMID- 8504451 TI - [Cohort study of HIV infection among drug users in Ruili City and Longchuan County, Yunnan Province, China]. AB - In March 1992, KAP investigation and HIV blood test were carried out for 860 drug users and 82 spouses in Ruili, Luxi, Longchuan of Yunnan Province, China. The results show that there were 285 IDUs (33.1%) among 860 drug users. Among 282 blood samples of IDUs, the HIV infection rate was 49.0%, highest in Ruili (81.8%, 63/77), then Longchuan (44.6%, 77/166), lowest in Luxi County (5.1%, 2/36). Twelve new HIV+ were found from 75 persons, who had been tested as HIV- in recent two years. Sixty-two blood samples were collected among 82 spouses of IDUs with HIV+, 6 were HIV+ (9.8%), with an increase of 6.7% comparing with results of the investigation two-years ago (3.1%, 2/64). PMID- 8504452 TI - [Investigation on distribution and changes of Shigella group in Fengtai district, Beijing from 1979 to 1991]. AB - A total of 386 strains of Shigella were collected and identified by biochemistry and serotyping from 1978 to 1991. Results showed that the strains were distributed in 4 groups which included 20 serotypes.S.flexner was predominant, mainly 2a and 3a serotypes, and S.sonnei the next. The ratio of B group to D group was 4.3. PMID- 8504453 TI - [Analysis of personality characteristics among 78 opiate addicts]. AB - A 1:1 pair-matched case-control survey was carried out to study the deviation in personality of 78 pairs of opiate addicts. The results showed that the scores of opiate addicts tested by subscales of Hypochondriasis (Hs), Psychopathic Deviate(Pd), Paranoia(Pa), Psychasthenia (Pt), Schizophrenia(Sc), Hypomania(Ma), Prejudice(Pr), Anxiety(A), Manifest Anxiety Scale(Mas), Dependency(Dy), Control(Cn) were higher than those of the controls (P < 0.05). The scores of the addicts on Ego Strength(Es), Social Status(St), Dominance(So), Social Responsibility (Re) scales were lower than those of the controls. This implied that there was a significant correlation between opiate abuse and abnormal personality. PMID- 8504454 TI - [Detection antigen of Rickettsia tsutsugamushi by using monoclonal antibody]. AB - Dot-ELISA was used with HRP-labelled monoclonal antibodies Kp3 (IgGi) and Kp4-6 (IgM) against antigen of the Karp strain of Rickettsia tsutsugamushi to detect the antigen of R. tsutsugamushi. The positive rate of sera of 56 acute scrub typhus patients and 37 wild rats caught from the countryside of the endemic area as well as 29 batches of chiggers collected from the wild rats were 92.9%, 100% and 89.7%, respectively. No cross reaction was found with antigens of other rickettsia groups such as R. mooseri, R. prowazeki, R.burneti and R. rickettsia. In patients suffering from acute scrub typhus the antigen of R. tsutsugamushi could be detected earlier in the course of illness than the antibody. This method is very sensitive that an amount of antigen of 6.7ng/microliters can be detected. It is easy to perform and the results can be read by naked eye. PMID- 8504455 TI - [Advances in the research of human cryptosporidosis in China]. PMID- 8504456 TI - [Serum cholesterol and cancer mortality: eleven-year prospective cohort study on more than nine thousand persons]. AB - Nine thousand and twenty-one employees aged 35-64 years were investigated in the 70s in the meantime with serum cholesterol and other measurements taken, and followed up for 11 years on the average. There were 595 deaths and 64 loss of follow-up. The total number of cancer death was 263 that of primary liver cancer was 51. Subjects were divided into 4 similar sized groups according to serum cholesterol level at basal measurement. No evidence of association of serum cholesterol level with total cancer mortality was seen by Log-rank trend test. But negative correlation was significant between serum cholesterol level and liver cancer (P < 0.05). By Cox regression analysis such negative correlation was found to be independent of other variables (Z = -2.18, P < 0.05). This negative correlation persisted even after 14 deaths of primary liver cancer which occurred within 3 years after measurement of serum cholesterol was discounted. Similar negative correlation also existed between serum cholesterol level and chronic hepatitis and liver cirrhosis. PMID- 8504457 TI - Transitional expression of neural cell adhesion molecule isoforms during chicken embryonic myogenesis. AB - The neural cell adhesion molecule, NCAM, is known to be expressed in chicken muscle as at least three principal molecular forms (molecular masses of 155 kDa, 145 kDa, and 120 kDa). They are generated from a single gene by alternative splicing. To distinguish these molecular species and to investigate their expressions in muscle differentiation during chicken embryonic development, we prepared antipeptide antibodies against three different domains of the NCAM. The antibody named MSD<+> was designed to detect muscle-specific domain (MSD) which was inserted into a muscle-specific NCAM by alternative splicing. The locus encompassing the MSD insertion site was detected with the antibody named MSD<->, and cytoplasmic sites near the transmembrane region were detected with the antibody named CYT. Immunoblot analysis utilizing the peptide antibodies prepared here revealed that, of three NCAMs, two isoforms, 155 kDa and 120 kDa, were recognized with the antibody MSD<+> and the same 155-kDa and the other 145-kDa molecule were recognized with the antibody CYT. The antibody MSD<-> was capable of detecting all three isoforms of the NCAM. Expression of the 120-kDa form with MSD but lacking a cytoplasmic tail increased but that of the 145-kDa form with cytoplasmic tail but lacking MSD declined during embryonic day 5 to day 18. The 155-kDa form NCAM with both MSD and cytoplasmic tail was expressed specifically and transiently during embryonic day 11 to day 14 in chick muscle; this period coincides with the period of extensive myotube formation. Thus, this largest isotype seems to play an important role in muscle differentiation. PMID- 8504458 TI - Cell photodamage, a potential hazard when measuring cytoplasmic Ca2+ with fura-2. AB - Photodamage of insulin-releasing pancreatic beta-cells during measurements of the cytoplasmic Ca2+ concentration ([Ca2+]i) with fura-2 was studied. Keeping the fluorescence intensities at low levels, regular oscillations of [Ca2+]i with a frequency of 0.2-0.5 min-1 could be recorded for more than 60 min in glucose stimulated cells. However, after a tenfold increase of the excitation energies, oscillations disappeared in most cells, the glucose response being transformed into an elevated concentration of [Ca2+]i with irregular fluctuations. Under corresponding conditions, the loss of fluorescence due to photobleaching during the initial 10 min increased from 7 to 16% in cell-sized fura-2-containing droplets. In further attempts to investigate the effects of photodamage, cells were irradiated by pulses (< 1 ms) of intense UV light (300-400 nm). A single flash of 4-7 mJ/mm2 perturbed the oscillatory pattern with maintenance of the glucose response in terms of raised [Ca2+]i. More severe lesions obtained by repeated pulses of 13-15 mJ/mm2 involved an excessive and uncontrolled rise of [Ca2+]i. It is concluded that there is a significant potential risk of photodamage when using the fura-2 technique. In the pancreatic beta-cells, exposure to intense excitation light may even result in a selective suppression of the oscillatory response to glucose. PMID- 8504459 TI - Intracellular localization of UDP-glucuronosyltransferase expressed from the transfected cDNA in cultured cells. AB - Liver UDP-glucuronosyltransferase (UDPGT) is localized in the endoplasmic reticulum (ER), with its catalytic domain exposed to the lumenal side of the membrane structure. The proteins expressed from the transfected UDPGT cDNA in cultured cells were found to be localized in the ER membrane. Its enzyme activity was in a latent state and was fully expressed in an in vitro assay system when the membrane integrity was disrupted by a detergent, Triton X-100, suggesting that the orientation of the expressed enzyme in the membrane was the same as that of the liver enzyme. To investigate how the expressed UDPGT was retained in the ER, we constructed chimeric plasmids of cDNAs of UDPGT and ErbB2 which is a receptor protein localized in the cell membranes. Analysis of chimeric proteins expressed in the stable transformants of the cultured cells transfected with these plasmids to reveal that the cytoplasmic tail of UDPGT is responsible for the ER retention of the expressed proteins. Deletion and mutation analysis in the cytoplasmic tail of the enzyme demonstrated that the two lysine residues positioned at 3 and 5 from the C-terminus of the molecule are important for conferring the ER residency. Furthermore, the distance of the ER retention signal composed of the two lysine residues from the transmembrane domain may be influential for the efficiency of the ER retention activity. PMID- 8504460 TI - Characterization of cell-adhesive proteins secreted by cell lines growing in protein- and lipid-free synthetic medium: mouse L.P3 cells secrete a procollagen molecule with potent cell-attachment activity. AB - We have previously shown that mouse L.P3 cells secrete fibronectin and a novel protein, gelatin-non-binding and heparin-binding cell-adhesive protein (GNCP). Here, we screened and characterized cell-adhesive proteins in the conditioned media (CM's) of a series of cell lines growing in a protein- and lipid-free synthetic medium (P3 cell lines). Although cell-attachment activity of the CM's ranged from undetectable to highly significant, fractionation with affinity columns revealed the presence of significant cell-attachment activity in all CM's. Using cell-attachment assay and immunoassay on blotted filters, various cell-adhesive proteins were detected in the CM's, and most of them were identified as fibronectin, laminin, vitronectin, and collagen. GNCP-like proteins were detected in the CM's of HeLa.P3, JTC-16.P3, L.P3, and JTC-12.P3. There was no relationship between the origin of the cell lines and the cell-adhesive proteins secreted. GNCP purified from L.P3-CM was separated into 120-, 140-, 150 , and 160-kDa proteins on SDS-PAGE, which were judged to be a type of mouse type I procollagen from the following results: (1) they were digested by collagenase, (2) pepsin treatment converted the 150- and 160-kDa proteins into 120- and 140 kDa proteins, (3) they were recognized by anti-type I collagen antiserum, and (4) amino-terminal sequence of the pepsin-digested 140-kDa protein had significant homology with type I collagen. GNCP showed half-maximum activity of cell attachment at 0.03 micrograms/ml, indicating that GNCP was a cell-adhesive protein with an extremely high specific activity compared to other known cell adhesive proteins. PMID- 8504461 TI - A synthetic C22 carotenoid inhibits carcinogen-induced neoplastic transformation and enhances gap junctional communication. AB - In 10T1/2 cells several dietary carotenoids have previously been shown to be capable of inhibiting carcinogen-induced neoplastic transformation. Two synthetic novel compounds, a C22 carotenoid, C22-polyene-tetrone-diacetal, and a C28 carotenoid, C28-polyene-tetrone, have now been tested in this system. The C22 compound was active in completely inhibiting 3-methylcholanthrene-induced transformation at 10(-5) M when added during the post-initiation phase of carcinogenesis. Gap junctional intercellular communication was strongly upregulated at this concentration. This activity has previously been shown to be highly correlated with, and has been proposed to be mechanistically linked to, inhibition of transformation by carotenoids in 10T1/2 cells. In contrast, the C28 compound, previously reported to be more active as a singlet oxygen quencher than C22, did not demonstrate activity in 10T1/2 cells in either assay system. This lack of activity was not due to chemical instability or lack of cellular uptake: the C28 compound was more stable in cell culture medium over 7 days and achieved higher cellular levels than the C22 compound (5 x 10(-11) mol/10(6) cells versus 0.5 x 10(-11) mol/10(6) cells). The activity of the C22 compound was not due to toxicity, since transformation occurred in carcinogen-treated cultures after its removal; neither was it due to antiproliferative effects on transformed cells, since the C22 compound did not prevent focus formation by transformed cells in reconstruction experiments. The demonstration that synthetic carotenoids possess biological activities comparable to the most potent naturally occurring compounds suggest that rational synthesis of compounds with improved pharmacological properties should be possible. PMID- 8504462 TI - Effects of cytosol on mutagenesis induced by N-nitrosodimethylamine, N nitrosomethylurea and alpha-acetoxy-N-nitrosodimethylamine in different strains of Salmonella: evidence for different ultimate mutagens from N nitrosodimethylamine. AB - N-Nitrosodimethylamine (NDMA), but not N-nitroso-N-methylurea (MNU) was more mutagenic in the Salmonella hisG428 strain, TA104, than in the hisG46 strain, TA100 in the presence of rat or hamster liver S-9 mix. As both NMDA and MNU can give rise to methyldiazonium ion (MDI) it appears that NDMA can be metabolized to an additional mutagen with a higher activity in TA104. The effects of UV and error-prone repair on NDMA and MNU-induced mutagenesis in TA104 were also different. alpha-Acetoxy-NDMA, which gives rise to the NDMA metabolite, alpha hydroxy-NDMA, was more mutagenic in TA104 than TA100, under certain conditions. Several metabolites of NDMA (formaldehyde, 1,1-dimethylhydrazine and nitrite) were not significantly mutagenic at the concentrations that could have been generated from NDMA. It was previously reported that the microsomal-mediated mutagenesis induced by NDMA is greatly increased by cytosol in TA104, but not in TA100. The current study found that when cytosol was separated into a high and a low mol. wt fraction, neither greatly enhanced microsomal-mediated mutagenesis by NDMA in TA104. Addition of NAD to the high, but not the low mol. wt fraction resulted in greatly enhanced activation of NDMA to a mutagen in TA104. The enhancement by cytosol of NDMA-induced mutagenesis in hisG428 was only observed when both microsomes and cytosol were simultaneously present. These observations indicate that (i) the precursor to the ultimate mutagen is relatively short lived; and (ii) the metabolism of alpha-hydroxy-NDMA to a secondary mutagenic metabolite, possibly N-nitroso-N-methylformamide, by alcohol dehydrogenase may be responsible for the ultimate mutagen with relatively high activity in TA104. PMID- 8504463 TI - The hepatic metabolism of two methylquinolines. AB - The hepatic microsomal metabolism of the carcinogenic 8-methylquinoline (8MQ) and its noncarcinogenic isomer, 6-methylquinoline (6MQ), were compared for preparations from control rats and rats pretreated with phenobarbital or 3 methylcholanthrene. For each compound the alcohol was the major metabolite, constituting 50-75% of 6MQ metabolites and 60-85% of 8MQ metabolites. Three phenols for 6MQ and two for 8MQ were seen. The latter formed two dihydrodiols which constituted 1-5% of metabolites while dihydrodiol products were not identified for the nontumorigenic 6MQ. Epoxides were observed for 6MQ while 8MQ afforded an N-oxide. PMID- 8504464 TI - Fluorescence HPLC methods for detecting benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide deoxyadenosine adducts in enzyme-digests of modified DNA: improved sensitivity. AB - The fluorescence of mononucleoside adducts derived from the binding of anti-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (BPDE I) to N6-deoxyadenosine (BPDE-dA adducts) is 10-100 times stronger (depending on the methanol/water solvent composition) than the fluorescence of adducts derived from the binding of this diol epoxide derivative to N2 deoxyguanosine. It is shown here that these fluorescence characteristics can be used to quantitate the relatively low yields of BPDE-dA adducts by fluorescence detection when BPDE-modified DNA is subjected to enzymatic degradation to the mononucleoside levels, followed by HPLC analysis of the digests. PMID- 8504465 TI - Detection of metabolites of polycyclic aromatic hydrocarbons in human urine. AB - A non-invasive assay has been developed for the recovery of r-7,t-8,t-9,c-10 tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]-pyrene (BP-7,10/8,9-tetrol) from human urine. This tetrol is excreted as a metabolite of benzo[alpha]pyrene (BP) in a process catalyzed by cytochrome P450 enzymes and epoxide hydrolases. Urine was hydrolysed to release activated benzo[alpha]-pyrene-diol-epoxides covalently bound to macromolecular species or conjugated tetrols. The relatively non-polar organic molecules from urine hydrolysates were collected on octadecasilane chromatography columns (Sep-Paks). Materials eluted in solvent (80% CH3OH), were further purified on immunoaffinity columns with antibodies raised against anti-N2 [10(7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo [alpha]pyrenyl)]-guanosine. HPLC was then used to isolate BP-7,10/8,9-tetrol, which was quantitated by synchronous fluorescence spectroscopy (SFS). This assay detected 0.24-3.12 pmol BP-7,10/8,9 tetrol per ml urine (limit of detection 0.01 pmol/ml, given 10 ml urine), in four study subjects. Reproducibility was assessed by adding tritium labeled BP 7,10/8,9-tetrol (1500 fmol) to a urine sample previously identified to contain the tetrol at levels below the limit of detection of the fluorescence assay; a recovery of > 30% of the added radioactivity was achieved (510 +/- 64 fmol, mean +/- SD, n = 3). Because HPLC alone was not sufficient to isolate materials for quantitation by SFS directly from human urine, immunoaffinity chromatography was found to be a necessary preparatory step in BP-7,10/8,9-tetrol isolation. These data demonstrate the presence of tetrahydrotetrol metabolites of BP in human urine and suggest that measurement of BP-7,10/8,9-tetrol and other polycyclic aromatic hydrocarbon-tetrols may prove to be valuable dosimeters of human internal exposure to polycyclic aromatic hydrocarbons. PMID- 8504466 TI - Depletion of O6-methylguanine-DNA methyltransferase and potentiation of 1,3-bis(2 chloroethyl)-1-nitrosourea antitumor activity by O6-benzylguanine in vitro. AB - The overcoming effect of O6-benzylguanine on O6-methylguanine-DNA methyltransferase (MGMT)-mediated 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance in vitro was evaluated. Depletion of MGMT activity in Mer+ HeLa S3 cells by O6-benzylguanine was dose-dependent and a complete loss of MGMT activity was achieved at a concentration of 0.5 microM. The cytotoxic potential of BCNU on MGMT proficient HeLa S3 (1.10 pmol/mg of protein), SMMC-7721 (0.72 pmol/mg of protein) and Cc801 (0.39 pmol/mg of protein) was greatly enhanced when cells were exposed to 10 microM O6-benzylguanine for 1 h, but there was a lack of potentiation of BCNU sensitivity in Mer- HeLa MR cells due to its nearly undetectable level of MGMT. There existed a correlation between the extent of enhancement and the amount of MGMT activity. The intensity of enhancement expressed as dose modifying factor = IC50 (BCNU alone)/IC50 (10 microM O6 benzylguanine + BCNU) was 4.56, 3.89, 3.67 and 0.97 in HeLa S3, SMMC-7721, Cc801 and HeLa MR cells respectively. The results further demonstrated that O6 benzylguanine may have potential utility as an adjuvant in combination chemotherapy with chloroethylnitrosourea agents. PMID- 8504467 TI - Malignant transformation of a mouse liver epithelial cell line by transfection of an activated c-H-ras gene with a point mutation at codon 12. AB - In order to scrutinize the reason why in mouse liver system only activated H-ras gene with a point mutation at codon 61 but not codon 12 is frequently seen although the latter mutation is highly frequent in methylnitrosourea-induced rat mammary tumors, transforming activity of these two types of mutated H-ras gene was investigated utilizing an immortalized but not fully transformed mouse liver epithelial cell line MLE-10, established in our laboratory. MLE-10 cells were transfected with activated human c-H-ras gene having a point mutation at either codon 12 (PT24) or 61 (PSK2), together with PSV2neo, or with PSV2neo only. G418 resistant colonies, propagated separately, gave rise to 6, 3 and 6 lines respectively. All the PT24 and PSK2-transfected cell lines were growth capable in both soft agar and nude mouse subcutis, with similar growth rate and morphological features whereas none of the cell lines transfected with the PSV2neo only revealed such growth capability. The results thus revealed that c-H ras with a mutation at codon 12 has oncogenic activity to the mouse hepatocyte, although after immortalization, at the degree similar to the same gene with a mutation at codon 61. PMID- 8504468 TI - Induction of mutations in mouse FM3A cells by treatment with riboflavin plus visible light and its possible relation with formation of 8-hydroxyguanine (7,8 dihydro-8-oxoguanine) in DNA. AB - Photosensitized formation of 8-hydroxyguanine (oh8Gua; 7,8-dihydro-8-oxoguanine, oxo8Gua) in cellular DNA and its repair was examined in mouse FM3A cells. oh8Gua was generated 7-fold above the background level by 10 min irradiation with visible light in the presence of riboflavin (160 microM0 and repaired to 60-70% of initial level after 2 h post-incubation. By this treatment, mutation frequency that was measured by counting ouabain-resistant colonies, was increased 7-fold above the background frequency. The accumulation of unrepaired oh8Gua in DNA generated by treatment with riboflavin plus visible light correlates to induction of mutations. Thus, oh8Gua will contribute to the mutation induced by visible light as well as spontaneous mutations. PMID- 8504469 TI - Methylene chloride-induced tumorigenesis. PMID- 8504470 TI - Mutational specificities of environmental carcinogens in the lacI gene of Escherichia coli. VI: Analysis of methylene chloride-induced mutational distribution in Uvr+ and UvrB- strains. AB - To better understand the mechanisms of mutagenesis by the carcinogen, methylene chloride (DCM), we have determined the nature and distribution of forward mutations induced by DCM in the N-terminal region of the lacI gene of Escherichia coli. A total of 116 lacI-d mutations (50 from Uvr+, 66 from UvrB- strain) were characterized by DNA sequencing. Both similarities and differences were observed. Although in both strains base substitutions predominated (74-88%) the distribution among the classes differed. In the case of the Uvr+ strain, DCM substantially increased the frequency of G:C-->C:G transversion and duplication events. Direct repeats were not observed at the endpoints of the duplications, however, all endpoints were in an A:T-rich region. In contrast, in the UvrB- strain, DCM induced A:T-->G:C, A:T-->C:G, G:C-->C:G events as well as deletions. The mutational spectra presented here represent a first step in the elucidation of the mechanism(s) of DCM-induced mutation. PMID- 8504471 TI - Ras proto-oncogene activation in liver and lung tumors from B6C3F1 mice exposed chronically to methylene chloride. AB - Methylene chloride has been the subject of recent toxicological and carcinogenesis studies because of significant human exposure and widespread use in industrial processing, food preparation and agriculture. In this study, liver and lung tumors, induced in female B6C3F1 mice by inhalation of 2000 p.p.m. methylene chloride (6 h/day, 5 days/week continuous exposure), were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 49 spontaneous and 50 methylene chloride-induced liver tumors and screened by oligonucleotide hybridization of PCR amplified H-ras gene fragments for codon 61 mutations. In the chemically induced tumors, 38 mutations were detected, 16 C to A transversions in base 1, 16 A to G transitions in base 2 and 6 A to T transversions in base 2. This mutation profile was similar to that identified for the H-ras gene in the spontaneous liver tumors and suggests that methylene chloride acts in liver by promoting cells with spontaneous lesions. Tumors in which H-ras codon 61 mutations were not detected were examined for the presence of transforming genes by the nude mouse tumorigenicity assay. Except for activated K-ras genes detected in DNA from two methylene chloride induced tumors and one spontaneous tumor, no other transforming genes were identified. DNA from 54 lung tumors was screened by direct sequencing of PCR amplified DNA fragments of the K-ras gene for first and second exon mutations, and 12 mutations were identified, 5 in exon one and 7 in exon 2. The low number of spontaneous tumors available in this study limits the interpretation of the data, and thus the frequency and spectrum of K-ras activation in the methylene chloride induced tumors was not significantly different from that in the seven spontaneous tumors analyzed. Since K-ras activation was not detected in 80% of the tumors, the nude mouse tumorigenicity assay was used to examine the lung tumors for the presence of other transforming genes. At present no transforming genes other than ras genes were identified in either liver or lung tumors. PMID- 8504472 TI - Characterization of p53 mutations in methylene chloride-induced lung tumors from B6C3F1 mice. AB - Mutations of the p53 tumor suppressor gene are the most common defined genetic alterations seen in a wide variety of human cancers. In contrast, little is known about the importance of the p53 gene in chemically induced tumors of rodents, which are widely used as models for the evaluation of human health risks. In this study we examined 54 methylene chloride-induced and seven spontaneously arising lung tumors from female B6C3F1 mice for losses of heterozygosity (LOH) at markers near the p53 gene on chromosome 11. LOH was detected in seven methylene chloride induced lung carcinomas by Southern analysis of a restriction fragment length polymorphism and PCR analysis of five simple sequence length polymorphisms. In each case allele loss was observed at all six markers; thus, these chromosomal alterations were likely to have resulted from mitotic nondisjunction. In contrast, LOH was not detected in 20 liver tumors from methylene chloride-treated mice at the Acrb locus, which is tightly linked to the p53 gene on chromosome 11. In addition single strand conformation polymorphism analysis was performed to screen for mutations in the most conserved regions of the p53 gene (exons 5 to 8). Consequently, potential mutations identified by direct sequencing, were only detected in four of the seven tumor samples with LOH, but not in any of the remaining lung tumors. Overexpression of the p53 protein by immunohistochemical staining was detected only in the four tumors that contained p53 point mutations and in a focal area of another tumor. Finally, using a simple sequence length polymorphism within the retinoblastoma tumor suppressor gene, LOH on mouse chromosome 14 was also detected in three lung carcinomas and one liver tumor. Inactivation of p53 and possibly the retinoblastoma tumor suppressor gene appear to be infrequent events in lung and liver tumors from methylene chloride treated mice. PMID- 8504473 TI - Effect of varying exposure regimens on methylene chloride-induced lung and liver tumors in female B6C3F1 mice. AB - Methylene chloride is a high production chemical used in a variety of applications resulting in estimated occupational and consumer exposures of at least one million people per day. Results of previously reported chronic evaluations of inhaled methylene chloride indicated that it caused mammary tumors in Fischer 344 rats and neoplasia in the lungs and liver of B6C3F1 mice. Mechanism(s) for methylene chloride-induced carcinogenesis have not been adequately elucidated. In this paper we describe the histologic evaluation of animals at a number of intermittent times for the purposes of assessing the progressive development of liver and lung neoplasia. Additionally, a series of stop-exposure treatments was conducted to evaluate the role of different methylene chloride exposure durations on the induction of hepatic and pulmonary neoplasia in female mice. Inhalation exposure to 2000 p.p.m. methylene chloride for 6 h per day, 5 days per week, for 104 weeks resulted in an 8-fold increase in the incidence of exposed animals having a lung adenoma or carcinoma (63 versus 7.5%; P < 0.01) and a 13-fold increase in the total number of pulmonary adenomas and carcinomas per animal at risk (0.97 versus 0.075; P < 0.01). This exposure also caused a 2.5-fold increase in the incidence of mice having liver tumors (69 versus 27%; P < 0.01) and a 3-fold increase in the total number of hepatic adenomas and carcinomas per animal at risk (1.34 versus 0.46; P < 0.01). Methylene chloride exposure hastened the first appearance of lung tumors (by 1 year) compared to that observed in control animals; chemical-induced and spontaneous liver tumors first occurred simultaneously. A shorter exposure duration was sufficient to attain maximal numbers of lung tumors than that needed for a maximal liver tumor burden. Lung tumor multiplicity was substantially increased by having additional time after cessation of the chemical treatment. This contrasts with the findings in liver, where additional post-exposure latency time did not effect tumor multiplicity compared to that of mice evaluated immediately after cessation of exposure. The incidence of lung alveolar hyperplasia in methylene chloride exposed animals was very low, even in tumor bearing animals and the hyperplasias were not seen until at least 13 weeks after appearance of adenomas and carcinomas. Thus, the genesis of methylene chloride induced lung tumors in B6C3F1 mice is not preceded by overt cytotoxicity, enhanced cell proliferation nor observed hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504474 TI - Expression and stability of p53 protein in normal human mammary epithelial cells. AB - To examine the p53 protein expressed in human mammary epithelial cell strains grown in vitro we first established the presence of only wild-type p53 and lack of any missense mutations in a representative normal mammary epithelial cell strain, 76N, by cloning and sequencing the entire coding region of the p53 mRNA. The p53 protein expressed in this cell strain and a number of similarly derived normal mammary epithelial cell strains was compared with mammary epithelial tumor cell lines having known p53 mutations and with fibroblasts derived from normal mammary tissue. In all cell strains, immunoprecipitation from metabolically labelled cells using monoclonal antibodies (mAb) PAb 1801 and PAb 122 revealed easily detectable p53 protein. Surprisingly, mAb PAb 1620 (wild type-specific) and PAb 240 (mutant-specific) each immunoprecipitated p53 protein from both normal and tumor cells. Furthermore, p53 protein in normal mammary epithelial cells was shown to be markedly more stable (half-life of approximately 3 h) compared to that in mammary fibroblasts or rodent fibroblasts (half-life < 30 min). Immunocytochemistry with PAb 1801 showed detectable p53 protein in normal mammary epithelial cells with a predominantly nuclear staining; however, p53 protein was undetectable in fibroblasts by immunocytochemistry. Together, these results reveal unusual features of wild-type p53 protein in normal human mammary epithelial cells, suggesting a cell type-specific regulation of its expression and function. PMID- 8504475 TI - p53 mutations in human immortalized epithelial cell lines. AB - Although rodent cells have been immortalized following transfection with a mutant p53 gene, the role of p53 in the immortalization of human cells is unknown. Therefore, human epithelial cell lines were examined for p53 mutations in exons 4 9 which include the evolutionarily conserved regions. A spontaneously immortalized skin keratinocyte cell line, HaCat, and three ras-transfected clones, have a p53 mutational spectrum that is typical of ultraviolet light induced mutations. A normal finite lifespan cell strain (184) and two benzo[a]pyrene immortalized mammary epithelial cell lines derived from 184 (184A1 and 184B5) contain wild type p53 sequences in exons 4-9, although elevated levels of nuclear p53 indicate an alteration in the stability of the normally transient protein. Wild type p53 was found in human bronchial, esophageal and hepatic epithelial cells immortalized by SV40 T antigen gene and human renal epithelial cells immortalized by adenovirus 5. BEAS-2B, an SV40 T antigen immortalized bronchial epithelial cell line and two subclones, have a germline polymorphism at codon 47. Inactivation of p53 by mechanisms such as mutation or complexing with proteins of DNA tumor viruses appears to be important in the immortalization of human epithelial cells. PMID- 8504476 TI - Protection against N-nitrosodiethylamine and benzo[a]pyrene-induced forestomach and lung tumorigenesis in A/J mice by green tea. AB - In recent years we and others have shown the cancer chemopreventive effects of green tea in several animal tumor models. In this study we assessed the cancer chemopreventive effects of water extract of green tea (WEGT) and the polyphenolic fraction (GTP) isolated from WEGT against N-nitrosodiethylamine (DEN)- and benzo[a]pyrene (BP)-induced forestomach and lung tumorigenesis in A/J mice. The protective effects, both in forestomach and lungs, were evident by a decrease in number of tumors and the percentage of mice with tumors when WEGT and GTP were fed to animals during initiation, post-initiation and entire period of tumorigenesis protocols. Oral feeding of 0.2% GTP in drinking water to mice afforded 68-82 and 39-66% protection against DEN- and BP-induced forestomach tumorigenesis respectively. In case of pulmonary tumor multiplicity caused by DEN and BP, the protective effects of GTP were between 38-43 and 25-46% respectively. Similarly, oral feeding of 2.5% WEGT to mice also afforded 80-85 and 61-71% protection against DEN- and BP-induced forestomach tumorigenesis respectively. In case of lung tumorigenesis, the protective effects of WEGT were 43-62 and 25-51% respectively. Histological studies of forestomach tumors showed significantly lower squamous cell carcinoma counts in GTP- and WEGT-fed groups of mice compared to carcinogen alone treated control group of mice. When pulmonary tumors were examined histologically, no adenocarcinomas were observed in GTP- and WEGT-fed groups of mice compared to 20% mice with adenocarcinomas in carcinogen alone treated control group. Oral feeding of GTP and WEGT in drinking water also showed significant enhancement in the activities of glutathione S-transferase and NADP(H): quinone reductase in liver, small bowel, stomach and lung. The results of this study suggest that green tea possesses chemopreventive effects against carcinogen-induced tumorigenesis in internal body organs, and that the mechanism of such effects may involve the enhancement of phase II and anti-oxidant enzyme systems. PMID- 8504477 TI - Inhibitory effects of curcumin on protein kinase C activity induced by 12-O tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells. AB - Curcumin is a dietary pigment responsible for the yellow color of curry. It is a potent inhibitor of tumor promotion induced by 12-O-tetradecanoyl-phorbol-13 acetate (TPA) in mouse skin. When mouse fibroblast cells (NIH 3T3) were treated with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microns curcumin for 15 min inhibited TPA-induced PKC activity in particulate fraction by 26 or 60% and did not affect the level of PKC protein. Curcumin also inhibited PKC activity in both cytosolic and particulate fractions in vitro by competing with phosphatidylserine. However, the inhibitory effect of curcumin was reduced after preincubation with the thiol compounds. These findings suggest that the suppression of PKC activity may contribute to the molecular mechanism of inhibition of TPA-induced tumor promotion by curcumin. PMID- 8504478 TI - Characterization of highly polar bis-dihydrodiol epoxide--DNA adducts formed after metabolic activation of dibenz[a,h]anthracene. AB - Dibenz[a,h]anthracene as well as a biologically important metabolite of dibenz[a,h]anthracene, namely the M-region dihydrodiol trans-3,4-dihydroxy-3,4 dihydrodibenz[a,h]anthracene were in addition to further metabolism to a bay region diol epoxide, extensively transformed to a distal bisdihydrodiol, 3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydro-dibenz[a,h]anthracene, which exhibited after renewed metabolic activation high DNA binding efficiency, leading to a new class of very polar DNA adducts. After incubation of dibenz[a,h]anthracene with DNA in the presence of liver microsomes from Aroclor 1254 treated male Sprague-Dawley rats highly polar DNA adducts probably originating from 3R,4R,10R,11R-tetrahydroxy-3,4,10,11-tetrahydrodibenz[a,h]an thracene and 3R,4R,10S,11S-tetrahydroxy-3,4,10,11-tetrahydrodibenz[a,h]anthr ace ne were identified by reversed phase HPLC and by the 32P-postlabeling method. The adducts obtained were further characterized by comparing their fluorescence spectra with those obtained from 3,4,10,11-tetrahydroxy- 3,4,10,11 tetrahydrodibenz[a,h]anthracene and from 3,4-dihydroxy-3,4 dihydrodibenz[a]anthracene, the putative chromophore of the polar adduct. DNA adducts formed via 3S,4S,10S,11S-tetrahydroxy-3,4,10,11-tetrahydro- dibenz[a,h]anthracene were not found. After incubation of 14C-labelled dibenz[a,h]anthracene highly polar DNA adducts derived from the bisdihydrodiol contributed 38% to the adducts found in the HPLC profile. Bay region diol epoxide adducts represented a fraction of 25%. Using the 32P-postlabelling technique a higher DNA binding yield for the racemic bisdihydrodiol (38 +/- 12 pmol/mg DNA) was calculated than for the most active 3,4-dihydrodiol enantiomer, 3R,4R dihydroxy-3,4- dihydrodibenz[a,h]anthracene (23 +/- 6 pmol/mg DNA). PMID- 8504479 TI - Biological activities of the intestinal microflora in mice treated with antibiotics or untreated and the effects of the microflora on absorption and metabolic activation of orally administered glutathione conjugates of K-region epoxides of 1-nitropyrene. AB - To elucidate the effects of the intestinal microflora on absorption and activation of glutathione conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), we investigated the biological activities of the microflora in specific-pathogen free (SPF) mice and SPF mice treated with various antibiotics and established the methodology of antibiotic treatment to eliminate the intestinal microflora. Mice were given various kinds of antibiotics by intragastric gavage twice a day for five days. A mixture of antibiotics bacitracin (BC), neomycin (NM) and streptomycin (SM) was the most effective in reducing the various activities of the intestinal microflora. The treatment decreased the bacterial counts and the activities of enzymes of the intestinal contents cysteine conjugate beta-lyase (beta-lyase), beta-glucuronidase and nitroreductase which were derived from the intestinal microflora, but did not affect the activities of gamma glutamyltransferase and aminopeptidase which were derived from host tissue cells. Furthermore, the treatment did not affect absorption of glucose from the intestinal tract, body weight or liver enzyme activities. The treatment with only an aminoglycoside antibiotic, kanamycin or NM, decreased neither the number of anaerobes in the intestine nor the beta-lyase or nitroreductase activities from the intestinal contents. Glutathione conjugates of [3H]-1-NP oxides were administered to two groups of ICR mice that had been treated with antibiotics (BC, NM, SM) or saline (control group) orally. The radioactivity in the blood increased and reached the maximum level 2 or 3 h after administration of the conjugates in the control group; however, that in the antibiotic-treated group was only slightly increased if at all. Excretion of [3H]-labeled metabolites into the urine was approximately 20% of the total dose in the control group, but it was < 2% in the antibiotic-treated group during 48 h. After 48 h, DNA in the lower intestinal mucosa was extracted and the DNA adducts were analyzed by the 32P-postlabeling method. Three new DNA adducts were detected in the lower intestinal mucosa of the control group but not of the antibiotic-treated group. These results suggest that the intestinal microflora plays an important role in absorption of the metabolites of glutathione conjugates of 1-NP oxides from the intestinal tract and activation of the metabolites in the intestine. PMID- 8504480 TI - Tumor-initiating activity and carcinogenicity of dibenzo[a,l]pyrene versus 7,12 dimethylbenz[a]anthracene and benzo[a]pyrene at low doses in mouse skin. AB - Dibenzo[a,l]pyrene (DB[a,l]P) is an extremely potent carcinogen that may be present in environmental samples. Dose-response studies were conducted at low doses in mouse skin by initiation-promotion and repeated application to compare its activity to that of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), DB[a,l]P-8,9-dihydrodiol and DB[a,l]P-11,12-dihydrodiol. Female SENCAR mice were initiated with 1 or 0.25 nmol of DB[a,l]P, DMBA, B[a]P or DB[a,l]P 11,12-dihydrodiol and promoted with phorbol ester acetate. At 1 nmol, DB[a,l]P induced 2.6 tumors/mouse, whereas DB[a,l]P-11,12-dihydrodiol and DMBA induced 0.17 and 0.29 tumors/mouse respectively. At the low dose, DB[a,l]P induced 0.79 tumors/mouse, but the other two compounds were virtually inactive. B[a]P, tested only at 1 nmol, was inactive. These three compounds, as well as DB[a,l]P-8,9 dihydrodiol, were tested by repeated application twice weekly for 40 weeks at 1 and 4 nmol per dose. In addition, DB[a,l]P, DMBA and B[a]P were also tested at 8 nmol. At 8 and 4 nmol, DB[a,l]P induced malignant tumors in 91 and 70% of mice respectively. At 4 nmol DB[a,l]P-11,12-dihydrodiol elicited only benign tumors in 36% of mice. At 4 nmol DMBA induced two carcinomas in one mouse and at 8 nmol it induced one papilloma and one sebaceous gland adenoma. B[a]P and DB[a,l]P-8,9 dihydrodiol were inactive at all doses tested. These results demonstrate that DB[a,l]P is a much more potent carcinogen than DMBA, the aromatic hydrocarbon previously considered to be the most potent. Combination of these results with previous comparisons of DB[a,l]P, DB[a,l]P-11,12-dihydrodiol, DMBA and B[a]P at higher doses (E.L. Cavalieri et al. (1991) Carcinogenesis, 12, 1939-1944) shows clearly the interference of toxicity with the tumorigenicity of DB[a,l]P and its 11,12-dihydrodiol. PMID- 8504481 TI - 3-Methylcholanthrene-inducible liver cytochrome(s) P450 in female Sprague-Dawley rats: possible link between P450 turnover and formation of DNA adducts and I compounds. AB - The hepatic cytochrome P450s are mixed-function oxidases which metabolize a wide variety of xenobiotics and endobiotics, and also bioactivate carcinogens such as 3-methyl-cholanthrene (MC) to reactive metabolites capable of forming DNA adducts. To investigate possible relationships between cytochrome P450 induction and covalent DNA modifications (adducts and I-compounds), female Sprague-Dawley rats were i.p. treated with MC (25 mg/kg) in corn oil (CO), once daily for 4 days. Controls received CO only. Animals were euthanized at 1, 8, 15, 28 and 45 days after the last MC treatment, and liver microsomal cytochrome P450, ethoxycoumarin O-deethylase (ECD) and ethoxyresorufin O-deethylase (EROD) activities were determined. Liver DNA adducts and I-compounds were analyzed by 32P-postlabeling. A significant induction of the levels of P450, ECD and EROD activities was noted in MC-treated rats, and elevated enzyme levels persisted for about 6 weeks after cessation of MC administration. Linear decay of total P450, ECD and EROD activities as a function of time was observed. MC induced 11 DNA adducts in liver, which were resolved by thin-layer chromatography (TLC) and persisted at high levels throughout the study. On the other hand, MC elicited a significant depletion of both non-polar and polar I-compounds (age-dependent DNA modifications detectable by 32P-postlabeling in rodent tissues without known exposure to carcinogens). Level of most I-compounds returned to normal at 45 days, and this paralleled the return of P450-related activities to normal. These results suggest a possible link between P450 turnover, DNA adduct formation, and I-compound depletion. PMID- 8504482 TI - Penetration of N-methyl-N'-nitro-N-nitrosoguanidine to proliferative cells in gastric mucosa of rats is different in pylorus and fundus and depends on exposure time and solvent. AB - We have studied the penetration of a labeled gastric carcinogen, N-(3H)methyl-N' nitro-N-nitrosoguanidine (3H-MNNG), from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats. 3H-MNNG was dissolved in deionized water or dimethyl sulfoxide (DMSO) and given intragastrically through a tube in the forestomach. Cells in the S-phase were labeled by incorporation of bromodeoxy uridine. Penetration of the carcinogen was evaluated by light microscopy after immunohistochemistry and autoradiography. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are considered to represent the cell population at risk of MNNG-induced carcinogenesis. When deionized water was used as solvent for the carcinogen, the average percentage of double-labeled cells in the pylorus was 12.0, 22.4 and 32.5 respectively, after 10, 30 and 60 min of mucosal exposure to 3H-MNNG. The corresponding percentages for the fundus mucosa were 1.7, 3.1 and 3.4, which are significantly lower than the pylorus values. When DMSO was used as solvent for the carcinogen, the percentage of double-labeled cells was 0.3 and 1.1 in the pylorus and 0.1 and 1.3 in the fundus after 10 and 30 min exposure to 3H-MNNG. Dimethyl sulfoxide caused superficial mucosal damage to the gastric mucosa and increased secretion of fluid into the stomach. Our results strongly suggest that gastric cancer develops in the pylorus because the carcinogen penetrates more easily into pyloric than fundic mucosa. The results support the view that delayed gastric emptying is a risk factor in gastric carcinogenesis, and show that DMSO counteracts the penetration of MNNG into the mucosa. PMID- 8504483 TI - Detection of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in beer and wine. AB - A carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was measured in beer and wine by HPLC. PhIP was found to be present in all brands of beer and wine analyzed. The concentrations of PhIP in beer and wine were 14.1 +/- 6.18 ng/l (mean +/- SD, n = 11) and 30.4 +/- 16.4 ng/l (n = 10) respectively. PMID- 8504484 TI - Repair of N-methylpurines in the mitochondrial DNA of xeroderma pigmentosum complementation group D cells. AB - Previous work from our laboratory has shown that mitochondria are able to repair N-methylpurines formed by methylnitrosourea (MNU). However, it is unclear as to whether repair mechanisms that remove this type of lesion in nuclear DNA also remove these adducts in mitochondria. To address this question, we studied repair of MNU-induced N-methylpurines in the mitochondrial DNA from xeroderma pigmentosum complementation group D (XP-D) cells using quantitative Southern blot analysis and 32P-end-labeling techniques. These cells have been reported to be defective in the repair of this type of lesion in their nuclear genome. WI 38 cells were used as normal controls for these studies. Both XP-D fibroblasts and WI 38 cells were exposed to 0.5 mM MNU for 1 h. Following an 8 h repair period, 61% of N-methylpurines were repaired in the mitochondrial genome of XP-D cells and 39% of these lesions were repaired in WI 38 cells. After 24 h, XP-D cells had repaired 77% of the N-methylpurines in their mitochondrial genome, while WI 38 cells had 44% repair of this type of damage. During this same 24 h time period, 81.5% of the N7-methylguanines had been removed from the total cellular DNA of the WI 38 cells compared to only 38.3% repair of this lesion in the XP-D cells. Thus, XP-D cells, though deficient in the repair of N-methylpurines in their nuclear genome, are proficient in the repair of this type of damage in their mitochondria, suggesting that the mechanisms to repair N-methylpurines in the nuclear and mitochondrial genomes of these cells are different. PMID- 8504485 TI - Deficient gene specific repair of cisplatin-induced lesions in Xeroderma pigmentosum and Fanconi's anemia cell lines. AB - Cisplatin is a chemotherapeutic agent known to cause DNA damage. The cytotoxicity of this drug is believed to result from the formation of DNA intrastrand adducts (IA) and DNA interstrand crosslinks (ICL). While there are many studies on DNA repair of cisplatin damage at the overall level of the genome in various human cell lines, there is little information on the gene-specific repair. In this report, we have measured the formation and repair of cisplatin induced DNA adducts in the dihydrofolate reductase (DHFR) and ribosomal RNA (rRNA) genes in three cell lines: normal human fibroblasts, Fanconi's anemia complementation group A (FAA) and Xeroderma pigmentosum complementation group A (XPA). It is generally thought that XPA cells lack nucleotide excision repair and that FAA cells are deficient in the repair of DNA ICL. We find that normal human fibroblast cells repair 84% of the ICL in the DHFR gene after 24 h, whereas XPA and FAA cell lines only repaired 32 and 50% of the ICL respectively. Furthermore, 69% of the cisplatin IA in the DHFR gene were repaired in 24 h in normal human fibroblasts compared to 22% for XPA and 24% for FAA cells. The repair of the rRNA gene was less efficient than in the DHFR gene, but the relative pattern between the different cell lines was similar to that of the DHFR gene. We thus find that FAA cells are deficient not only in the gene specific repair of cisplatin ICL, but also in the gene specific repair of the more common cisplatin IA. XPA cells are normally thought to be without any nucleotide excision repair capacity, but our data could support a slight ICL unhooking activity. PMID- 8504486 TI - Promoting effects of mancozeb on pancreas of nitrosomethylurea-treated rats. AB - Rats were treated with a single i.p. injection of the carcinogen nitrosomethylurea (NMU, 50 mg/kg b.w.) at day three of age. The treatment induced hyperplastic and atypical acinar cell proliferation [focal acinar cell hyperplasia (FACH)]. In this investigation, NMU treated rats were fed AIN-76 diet containing mancozeb (MZ; 100 mg/kg diet), a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, which is an agricultural fungicide. EXPERIMENTAL DESIGN: Group one was treated with NMU plus MZ (MZ-NMU), group 2 received NMU alone (NMU), group 3 was fed MZ and saline injected (MZ-SAL) and group 4 was the saline injected control (SAL). Rats were killed at week 24 of age. In MZ-NMU group pancreas there were FACH, dysplastic foci (DYF) and carcinomas in situ (CIS). FACH were larger, coalescent and may show areas of undifferentiated cells (focus within focus). DYF contain proliferative acinar and ductular structures with loss of polarity but no malignant traits. CIS had medullary appearance or consisted of irregularly shaped acini and ducts in stromal framework. Cell had scant cytoplasm and large hyperchromatic, pleomorphic nuclei. DYF and CIS were not seen in MZ group pancreas. The MZ-NMU group had increased mitotic index and greater number of apoptotic cells. There was no pathologic change in MZ-SAL group. Our data indicated that MZ did not cause pancreatic cell proliferation in normal rats whereas it had distinct promoting and progressor effects on NMU initiated pancreatic cells. Thus, a two-stage protocol of pancreatic carcinogenesis was achieved. It is suggested that the NMU protocol may be useful for testing promoter, progressor or inhibitory effect of chemical and physical agents on cell proliferation and transformation of rat pancreas. PMID- 8504487 TI - DNA crosslinking, sister chromatid exchange and cytotoxicity of N-2 chloroethylnitrosoureas tethered to minor groove binding peptides. AB - Chloroethylnitrosoureas (CENU) are clinically important chemotherapeutic agents whose mechanism of action involves the formation of interstrand DNA crosslinks via an ethane bridge between N1-G and N3-C. CENU generally alkylate G at the N7- and O6-positions, with the latter lesion being the precursor to the interstrand crosslink. In previous studies, we reported the synthesis of CENU appended by a C2H4 linker to the N-terminus of DNA minor groove binding dipeptides (lex, information reading peptides) based on N-methylpyrrole-carboxamide subunits. Because of the dipeptide structure, these CENU-lex's react with DNA at adenines associated with lex equilibrium binding sites. No other CENU has been reported to yield A adducts. The biological evaluation of these CENU-lex's show that they are somewhat less cytotoxic than their simpler counterparts. In addition, in vitro studies show that the minor groove binding CENU-lex's afford a lower level of sister chromatid exchange (SCE) in 9L cells that are sensitive to CENU. There is no difference between CENU-lex in SCE induction in 9L-2 cells that are resistant to CENU. Formation of DNA interstrand crosslinks from the CENU-lex's is lower than for their nonaffinity binding analogs in low ionic strength buffer, but similar in the same buffer containing 200 mM NaCl. Salt inhibits crosslinking for all CENU, but distamycin, a competitive inhibitor of lex minor groove binding, uniquely enhances crosslinks for the CENU-lex's. These results are consistent with the novel minor groove adduction being a 'detoxification' pathway for the CENU-lex's since this lesion is formed at the expense of the cytotoxic major groove interstrand crosslink. PMID- 8504488 TI - Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate. AB - Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta glycerophosphate. A number of cell lines have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen. PMID- 8504489 TI - 60 Hz magnetic field acts as co-promoter in focus formation of C3H/10T1/2 cells. AB - Disruption of communication between transformed cells and normal cells is involved in tumor promotion. We have tested the hypothesis that 60 Hz electromagnetic (EM) field exposures and a chemical tumor promoter, 12-O tetradecanoylphorbol-13-acetate (TPA) are co-promoters that enhance focus formation of transformed cells in co-culture with normal cells. EM field exposures alone did not affect the growth curves of parental C3H/10T1/2 fibroblasts or daughter mutant cells, UV-TDTx10e. Furthermore, EM field exposures alone did not promote focus formation of mutant cells in co-culture with parental cells under the conditions tested. However, EM field exposures co-promoted with TPA by increasing focus formation in co-culture. Cell cultures were exposed to an EM field in custom-built solenoidal incubators. The field exposures were 1.0 Gauss in a schedule of 1 h epochs four times daily for 28 days. Video image analysis of three independent experiments showed that field-exposed cultures produced 1.9-fold more foci than sham-exposed cultures when treated with TPA. The total area of foci per dish increased 2.2-fold and the number of cells in stained foci increased 2.3-fold. In a TPA dose-response, focus formation began at 3 ng/ml with no difference between field-exposed and sham-exposed co-cultures. However, at the TPA concentrations of 10, 20, 40, 50 and 100 ng/ml EM field exposures enhanced focus formation by an average of 150%. This study suggests that chronic intermittent exposures to a 60 Hz EM field and a chemical tumor promoter influenced membrane-related events by co-promoting focus formation. PMID- 8504490 TI - Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure. AB - Diabetes mellitus has been suggested as a possible risk factor for the development of pancreatic cancer in humans. Previous studies in our laboratory have shown, however, that streptozotocin (STZ) diabetes inhibits the development of cancer of the exocrine pancreas in hamsters when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). It has been reported by others that the concurrent administration of BOP and STZ enhances pancreatic carcinogenesis in hamsters. The purpose of the present study was to determine the effect of STZ diabetes on the development of BOP-induced pancreatic carcinoma when STZ is given following exposure to BOP. Groups of Syrian golden hamsters were treated with either BOP only (single s.c. injection, 40 mg/kg body wt at week 0), BOP (single s.c. injection, 40 mg/kg body wt at week 0) plus STZ (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), STZ only (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), or neither BOP nor STZ. The experiment was terminated at 40 weeks after BOP treatment. No significant difference was seen in the incidence of pancreatic cancer between those animals receiving BOP only at week 0 and those receiving BOP at week 0 plus STZ at weeks 10, 20 or 30 of the study. The results would appear to indicate that STZ diabetes, established after BOP tumor initiation, plays no apparent role in the modulation of pancreatic carcinogenesis. PMID- 8504491 TI - HPRT and glycophorin A mutations in foundry workers: relationship to PAH exposure and to PAH-DNA adducts. AB - Mutations were evaluated in workers in an iron foundry with exposure to polycyclic aromatic hydrocarbons (PAHs), measured by personal and area monitoring, ranging from < 5 to 60 ng/m3 of benzo[a]pyrene (B[a]P). Mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) and glycophorin A (GPA) loci (measures of molecular effect in lymphocytes and erythrocytes respectively) were assessed to demonstrate their relationship to external exposure at lower levels than previously analyzed in foundry workers at this plant (< 50-200 ng/m3). The relationship between mutations and PAH-DNA adducts measured by immunoassay (as a measure of the biologically effective dose) was also investigated. The markers were analyzed for dose-response and interindividual variability. Workers were classified into three exposure categories (low, medium and high). PAH-DNA adduct values for the low, medium and high exposure groups were 5.19, 6.10 and 9.57 x 10(-8) nucleotides respectively (r = 0.28; P = 0.08). HPRT mutant frequencies (adjusted for age and cloning efficiency) for the low, medium and high exposure groups were 1.04, 1.13 and 1.82 x 10(-6) cells respectively and demonstrated an upward trend with increasing exposure that was of borderline significance (r = 0.46, P = 0.06). In contrast, HPRT mutations were highly correlated with PAH-DNA adducts (r = 0.67; P = 0.004). Interindividual variability in mutant frequencies ranged from 1.5- to 4.5-fold within the three exposure categories. With respect to GPA variants, NN frequency (Vf) in erythrocytes (which reflects chromosomal loss and duplication, recombination or gene conversion) was not positively correlated with PAH exposure. The level of N0 Vf (arising from small-scale structural mutations in the GPA gene or from larger-scale chromosomal rearrangements or deletions) increased slightly, but not significantly, over the three exposure groups from 8.2 to 10.7 to 11.8/10(6) cells (P = 0.32). Interindividual variation in GPA NN Vf ranged from 2- to 18-fold and in GPA N0 from 4- to 5-fold. NN and N0 Vf were highly correlated (P = 0.001) but no correlation was seen between GPA and HPRT or between GPA and PAH-DNA adducts. Thus, the most interesting and novel finding is that, even at relatively low exposures to PAH, HPRT mutations were increased in parallel with PAH-DNA adducts. The observed association between PAH-DNA adducts and HPRT gene mutation in humans is consistent with experimental data for PAHs. These results support the use of both biomonitoring and personal ambient monitoring in further molecular epidemiology studies. PMID- 8504492 TI - Thiol status and cytopathological effects of acrolein in normal and xeroderma pigmentosum skin fibroblasts. AB - Thiol redox status was determined in normal human skin fibroblasts and a DNA repair-deficient xeroderma pigmentosum (XP) fibroblast cell line (XP12BE, group A), and cytotoxic and genotoxic effects of the thiol-reactive aldehyde acrolein were studied in these cell types. Normal cells contained higher amounts of the reduced glutathione and cysteine respectively, and higher amounts of these thiols as protein-bound disulfides than the XP cells. However, in both cell types total glutathione was present in 6- to 7-fold higher amounts than total cysteine, and total protein thiols corresponded to approximately 30% of total thiols. A 1 h exposure to acrolein caused a quantitatively similar depletion of reduced glutathione and free protein thiols in both cell types, without causing changes in the thiol redox state. However, acrolein caused higher toxicity measured as trypan blue exclusion, and also a higher extent of DNA single-strand breaks in the XP cells than in the normal cells. Exposure to acrolein, followed by incubation in fresh medium resulted in continued formation of DNA single-strand breaks in the normal cells, whereas no such accumulation occurred in the XP cells. In the normal cells, the DNA single-strand breaks accumulated to a similar extent as in the presence of 1-beta-D-arabinofuranosyl-cytosine and hydroxyurea, i.e. two agents which together efficiently inhibit DNA repair synthesis. The results indicate quantitative and qualitative differences in the thiol redox state between normal and XP cells, and that these differences may contribute to the higher cytotoxicity and genotoxicity of acrolein in XP cells. Moreover, the results indicate that acrolein is a potent inhibitor of DNA excision repair. PMID- 8504493 TI - Autocrine production of TGF-alpha and TGF-beta during tumour progression of rat oral keratinocytes. AB - This study describes a new technique to separate transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta) from culture supernatants using ion exchange chromatography; assays of competitive inhibition of ligand binding were used to quantify the amount of growth factor. The method was simple, inexpensive and did not require large volumes of culture medium. The autocrine production of TGF-alpha and TGF-beta was examined in oral keratinocyte cell lines derived from the palatal and lingual mucosa of rats painted with the carcinogen 4-nitroquinoline N-oxide (4NQO). Escape from cellular senescence (immortality) was associated with a marked increase in TGF-alpha production (cell line R2P) but tumour progression, as reflected by the development of anchorage independence in agarose gels and tumorigenicity in athymic mice, did not result in a consistent increase or decrease of TGF-alpha production compared to normals. Four cell lines (R8AP, R1T, R3T, R1P), with different functional cellular phenotypes, produced two to three times more TGF-alpha than normals. TGF-alpha production was inversely correlated to epidermal growth factor cell surface receptor expression. The autocrine production of TGF-beta was variable with the majority of cell lines producing markedly little TGF-beta; three cell lines (R4T, R8BP, R9T) produced more TGF-beta than normals. The production of TGF-beta was unrelated to tumour progression, the expression of TGF-beta cell surface receptors or TGF-alpha production. The results indicate that the autocrine production of TGF-alpha and TGF-beta are not accurate markers of tumour progression in the rat 4NQO model of oral carcinogenesis. PMID- 8504494 TI - Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. AB - The consensus of evidence from angiographic trials demonstrates both coronary artery and clinical benefits from lowering of lipids by a variety of regimens. The findings of reduced arterial disease progression and increased regression have been convincing but, at best, modest in their magnitude. For example, among those treated intensively in FATS, the mean improvement in proximal stenosis severity per patient was < 1% stenosis, and only 12% of all lesions showed convincing regression. In view of these modest arterial benefits, the associated reductions in cardiovascular events have been surprisingly great. For example, coronary events were reduced 75% in FATS; this was entirely a result of a 93% reduction in the likelihood that a mildly or moderately diseased arterial segment would experience substantial progression to a severe lesion at the time of a clinical event. We believe that the magnitude of the clinical benefit is best explained in terms of this observation, according to the following lines of reasoning. Clinical events most commonly spring from lesions that are initially of mild or moderate severity and then abruptly undergo a disruptive transformation to a severe culprit lesion. The process of plaque fissuring, leading to plaque disruption and thrombosis, triggers most clinical coronary events. Fissuring is predicted by a large accumulation of core lipid in the plaque and by a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics constitute only 10-20% of the overall lesion population but account for 80-90% of the acute clinical events. In the experimental setting, normalization of an atherogenic lipid profile substantially decreases the number of lipid-laden intimal macrophages (foam cells) and depletes cholesterol from the core lipid pool. In the clinical setting, intensive lipid lowering virtually halts the progression of mild and moderate lesions to clinical events. Thus, the reduction in clinical events observed in these trials appears to be best explained by the relation of the lipid and foam cell content of the plaque to its likelihood of fissuring and by the effects of lipid-lowering therapy on these "high-risk" features of plaque morphology. The composite of data presented here supports the hypothesis that lipid-lowering therapy selectively depletes (regresses) that relatively small but dangerous subgroup of fatty lesions containing a large lipid core and dense clusters of intimal macrophages. By doing so, these lesions are effectively stabilized and clinical event rate is accordingly decreased. PMID- 8504495 TI - TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction. Ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM-3 Study. AB - BACKGROUND: Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction. The Thrombolysis in Myocardial Infarction (TIMI) Study Group perfusion grades have gained wide acceptance, with grades 0 (no distal flow) and 1 perfusion (minimal flow) being designated as thrombolysis failures and grades 2 (partial perfusion) and 3 (complete perfusion) as thrombolysis successes. However, the significance of the individual TIMI grades on clinical outcome has not been adequately assessed. METHODS AND RESULTS: To evaluate the functional significance of TIMI perfusion grades, we compared 1-day coronary patency status with ventriculographic, enzymatic, and ECG indexes of acute myocardial infarction in 298 patients treated with anistreplase or alteplase within 4 hours of myocardial infarction symptom onset. Radionuclide ejection fraction was determined at 1 week and at 1 month. Perfusion grades for the entire study population were distributed as 12% (n = 37) grades 0/1, 13% (n = 40) grade 2, and 74% (n = 221) grade 3. Patency profile did not differ between the two thrombolytic regimens. Further coronary interventions were performed after the 1-day patency determination in 43% of patients (43%, 48%, 42%, respectively, in grades 0/1, 2, and 3 patients). The outcome of grade 2 patients did not differ from grades 0/1 patients in ejection fraction, enzyme peaks, ECG markers, or morbidity index. In contrast, grade 3 patients, compared with grades 0-2 patients, showed 1) a greater global ejection fraction at 1 week (54% versus 49%, p = 0.006) and at 1 month (54% versus 49%, p = 0.01), 2) a greater infarct zone ejection fraction at 1 week (41% versus 33%, p = 0.003) and at 1 month (42% versus 32%, p = 0.003), 3) smaller enzyme peaks, significant for lactate dehydrogenase, and shorter times to enzyme peaks, significant for all four enzymes, 4) a smaller QRS score at discharge and at 1 month, and 5) a trend toward a lower morbidity index. CONCLUSIONS: Grade 3 flow predicts significantly better outcomes than lesser grades of flow and represents an important measure of reperfusion success. PMID- 8504496 TI - Myocardial infarct size can be estimated from serial plasma myoglobin measurements within 4 hours of reperfusion. AB - BACKGROUND: An early estimation of infarct size is useful for the appropriate early treatment of patients with acute myocardial infarction. We evaluated how early and how accurately infarct size could be estimated from serial plasma myoglobin (Mb) measurements in patients with successful reperfusion. METHODS AND RESULTS: We measured plasma Mb and creatine kinase (CK) in 35 patients in whom reperfusion therapy was successfully performed. Blood samples were collected at 15-minute intervals for 2 hours after reperfusion, at 30-minute intervals for the subsequent 2 hours, and at 3-6-hour intervals until 52 hours after reperfusion. Plasma Mb was measured by a newly developed turbidimetric latex agglutination assay. Total Mb and CK release (sigma Mb, sigma CK) were calculated with a one compartment model. The mean chord motion in the most hypokinetic 50% of the infarct-related artery territory was calculated from follow-up ventriculograms as an index of the severity of regional hypokinesis. There were significant correlations between sigma Mb and sigma CK (r = 0.89), between log sigma Mb and the severity of regional hypokinesis (r = -0.85), and between log sigma CK and the severity of regional hypokinesis (r = -0.74). The time required for the cumulative Mb release curves to reach a plateau was 64 +/- 28 minutes. An additional 53 +/- 14 minutes was required to calculate the disappearance rate constant of Mb, and 15 minutes was necessary for the assay. Therefore, the total time required for sigma Mb to be available was 132 +/- 40 minutes, significantly shorter than the time required for sigma CK, 24.3 +/- 9.1 hours (p < 0.001). The infarct size could be estimated from the sigma Mb in 34 of 35 patients within 4 hours of reperfusion. CONCLUSIONS: Infarct size can be estimated accurately 4 hours after reperfusion by calculating the sigma Mb in patients with successful reperfusion. PMID- 8504497 TI - Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. AB - BACKGROUND: Staphylokinase (STA), a protein with known profibrinolytic properties, is produced by transduced Staphylococcus aureus strains. In experimental animal models, recombinant staphylokinase (STAR) is less immunogenic and more active toward platelet-rich arterial blood clots than streptokinase. METHODS AND RESULTS: In the present study, 10 mg STAR given intravenously over 30 minutes was found to induce angiographically documented coronary artery recanalization within 40 minutes in four of five patients with acute myocardial infarction. Plasma fibrinogen and alpha 2-antiplasmin levels were unaffected, and allergic reactions were not observed. Postinfusion disappearance of STAR antigen followed a biphasic mode with a t1/2 alpha of 6.3 +/- 0.6 minutes (mean +/- SD) and a t1/2 beta of 37 +/- 15 minutes, corresponding to a plasma clearance of 270 +/- 100 mL/min. Neutralizing antibodies against STAR could not be demonstrated at baseline and up to 6 days after infusion, but STAR neutralizing activity, which did not cross-react with streptokinase, was consistently demonstrable in plasma at 14-35 days. CONCLUSIONS: STAR can induce clot-selective coronary thrombolysis in patients with evolving myocardial infarction without concomitant induction of a systemic lytic state. STAR, a small protein that can be easily produced by recombinant DNA technology, may therefore offer promise for thrombolytic therapy in patients with thromboembolic disease. PMID- 8504498 TI - X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. AB - BACKGROUND: X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus in two families using molecular genetic techniques. METHODS AND RESULTS: Linkage analysis using 60 X-chromosome-specific DNA markers was performed in a previously reported large XLCM pedigree and a smaller new pedigree. Two-point and multipoint linkage was calculated using the LINKAGE computer program package. Deletion analysis included multiplex polymerase chain reaction (PCR). Dystrophin protein was evaluated by Western blotting with N-terminal and C-terminal dystrophin antibody. Linkage of XLCM to the centromeric portion of the dystrophin or Duchenne muscular dystrophy (DMD) locus at Xp21 was demonstrated with combined maximum logarithm of the scores of +4.33, theta = 0 with probe XJ1.1 (DXS206) using two-point linkage and +4.81 at XJ1.1 with multipoint linkage analysis. LOD scores calculated using other proximal DMD genomic and cDNA probes and polymerase chain reaction polymorphisms supported linkage. No deletions were observed. Abnormalities of cardiac dystrophin were shown by Western blotting with N terminal dystrophin antibody, whereas skeletal muscle dystrophin was normal, suggesting primary involvement of the DMD gene with preferential involvement of cardiac muscle. CONCLUSIONS: XLCM is due to an abnormality within the centromeric half of the dystrophin genomic region in heart. This abnormality could be due to 1) a point mutation in the 5' region of the DMD coding sequence preferentially affecting cardiac function, 2) a cardiac-specific promoter mutation that alters expression in this tissue, 3) splicing abnormalities, resulting in an abnormal cardiac protein, or 4) deletion mutations undetectable by Southern and multiplex polymerase chain reaction analysis. PMID- 8504499 TI - Dose-dependent effect of aspirin on carotid atherosclerosis. AB - BACKGROUND: Antiplatelet treatment with aspirin is well established as secondary prophylaxis after a transient ischemic attack or minor ischemic stroke, but the effect of aspirin treatment on the course of carotid atherosclerosis is unknown. We investigated the effect of aspirin on the initial stages of carotid atherosclerosis. METHODS AND RESULTS: Patients were recruited from a prospective, randomized, double-blind clinical trial to compare two doses of aspirin (900 mg versus 50 mg daily) with regard to restenoses after lower limb angioplasty. Of the 383 patients admitted to the angioplasty trial, 27 patients with 104 small carotid atheroma (< 50% lumen narrowing) were examined at entry and after 1 year of aspirin treatment with the use of a high-resolution ultrasound duplex system. Disease progression and regression were defined by a change of maximal plaque area (as measured by longitudinal ultrasound sections) of more than 2 SDs of the method. The change in plaque area was significantly different for the treatment groups: Average plaque size remained unchanged after treatment with 900 mg aspirin daily but increased markedly after treatment with 50 mg aspirin daily (p = 0.011). There were significantly more lesions in the 50-mg group showing progression than in the 900-mg group (23 plaques [47%] versus 13 plaques [24%], p = 0.025). Ultrasonic disappearance of a lesion was observed only in the 900-mg group in nine cases (seven soft plaques and two ulcerative plaques, p = 0.018). The six patients on 50 mg aspirin who continued smoking during the study showed significantly more progression compared with the seven nonsmokers in the 50-mg group (17 plaques [59%] versus six plaques [30%], p = 0.038). CONCLUSIONS: The results of our study indicate that aspirin treatment slows carotid plaque growth in a dose-dependent fashion, with a dose of 900 mg daily more efficient than 50 mg daily. PMID- 8504500 TI - Shock occurrence and survival in 241 patients with implantable cardioverter defibrillator therapy. AB - BACKGROUND: The purpose of this study was to determine the influence of clinical characteristics on shock occurrence and survival in 241 patients with implantable cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: Two hundred forty one consecutive patients underwent ICD implantation between November 1982 and November 1991 and were subsequently followed for 26 +/- 22 months (intention-to treat analysis). Actuarial incidence of "appropriate" shocks was 13%, 42%, and 63%, and the incidence of any spontaneous shocks was 15%, 51%, and 76% at 1, 3, and 5 years of follow-up, respectively. Poor left ventricular function (ejection fraction < or = 30%) was associated with an earlier occurrence of both appropriate and any spontaneous ICD shocks (p = 0.001). Appropriate and any spontaneous shocks occurred significantly later in patients who presented with cardiac arrest and in patients in whom only ventricular fibrillation but no uniform ventricular tachycardia was induced during preoperative programmed stimulation. In addition, amiodarone treatment at implant was associated with later occurrence of any spontaneous shocks. Cumulative survival from all-cause mortality including perioperative mortality was 84%, 62%, and 57%, and survival from arrhythmic death was 97%, 89%, and 83% at 1, 3, and 5 years, respectively. Ejection fraction < or = 30% was the best predictor of both total arrhythmic death (p = 0.019) and total mortality (p = 0.003). Antiarrhythmic therapy with class 1 agents at implant was also associated with a higher total mortality during follow-up (p = 0.023) but not with total arrhythmic death. Age, sex, underlying heart disease, clinical presentation, and preoperative response to programmed stimulation did not predict long-term survival. In addition, survival curves were similar for patients with and without spontaneous shocks. CONCLUSIONS: The majority of patients receive shocks during long-term follow-up. The occurrence of appropriate or any spontaneous shocks during follow-up is not associated with increased arrhythmic or total mortality consistent with effective prevention of sudden cardiac death with ICD therapy in this high-risk patient population. Although low ejection fraction is the strongest predictor of both shock occurrence and mortality during follow-up, no easy algorithm can be derived from the analyzed clinical characteristics to predict which patients will benefit most from ICD implantation. PMID- 8504501 TI - A prospective randomized repeat-crossover comparison of antitachycardia pacing with low-energy cardioversion. AB - BACKGROUND: Multiprogrammable antiarrhythmia devices can treat monomorphic ventricular tachycardia (VT) with autodecremental overdrive pacing and/or with low-energy cardioversion. These two methods provide the opportunity to decrease patient discomfort typically experienced with high-energy pulses. Although both therapies are known to be effective, controversy persists over their relative safety and efficacy. METHODS AND RESULTS: The purpose of this study was to examine the safety and efficacy of autodecremental overdrive pacing and low energy cardioversion in reproducibly terminating monomorphic VT in 24 patients with multiprogrammable antiarrhythmia devices. The protocol required that identical ECG morphology VT be reproducibly induced four times to assess the outcome of antitachycardia pacing and cardioversion twice for each patient in a randomized fashion. Each episode of VT was induced via the implanted device. Autodecremental overdrive pacing initially began with seven stimuli at 97% of the VT cycle length, decrementing by 10 msec per stimulus to a minimum coupling interval of 200 msec. If ineffective, autodecremental overdrive pacing was allowed to iterate three more times for a total of four pacing interventions. With each iteration, one stimulus was added to the pacing train. Similarly, with low-energy cardioversion, up to four therapeutic attempts were made, beginning with a 0.2-J pulse. If ineffective, pulse energy was increased to 0.4, 1.0, and finally 2.0 J. All interventions were automatic without human interference. VT (cycle length, 306 +/- 42 msec) was repeatedly terminated in 15 of 24 patients (63%) by autodecremental overdrive pacing and in 18 of 24 patients (75%) by low energy cardioversion (p = 0.53). Eight of the 24 patients (33%) had their VT terminated repeatedly by both therapies. VT accelerated to faster VT or ventricular fibrillation by autodecremental overdrive pacing in four of 24 patients (17%) and by low-energy cardioversion in five of 24 (21%) (p = 0.88). Only one of the 24 patients (4%) accelerated with both therapies. No patient was unaffected by either therapy. CONCLUSIONS: In the manner programmed, autodecremental overdrive pacing and low-energy cardioversion have similar efficacy and acceleration rates. Response to one therapy does not predict response to the other. PMID- 8504502 TI - Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis. AB - BACKGROUND: This report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: The study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tachycardia (VT), 24 as non-VT rhythms (atrial fibrillation, 13; supraventricular tachycardia, six; rate-sensing lead disruption, four; T wave oversensing, one), and only three as indeterminate rhythms. Based on the electrogram analysis, changes in tachycardia detection criteria and/or antiarrhythmic drug regimens were implemented and were associated with a reduction in the number of device responses for non-VT rhythms from 24 during the initial study period to three during 11.0 +/- 7.2 months of additional follow-up. CONCLUSIONS: ICD responses in the absence of symptoms are relatively common in third-generation devices with antitachycardia pacing capabilities. Despite potential limitations such as the effect of bundle branch block on the electrogram morphology during supraventricular tachycardia, the availability of electrogram storage capabilities allowed a presumptive diagnosis of the events precipitating asymptomatic device responses. Device reprogramming based on analysis of stored electrograms was associated with a dramatic reduction in the incidence of ICD responses for non-VT rhythms. PMID- 8504503 TI - Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart. AB - BACKGROUND: Recent studies examining mechanisms of defibrillation have focused on prolongation of graded cellular response duration during refractory period stimulation. This mechanism assumes that defibrillation shocks interact with ventricular cells during the process of repolarization. METHODS AND RESULTS: To test this assumption, we examined monophasic action potentials (MAPs) from 171 episodes of induced ventricular dysrhythmia associated with loss of systemic perfusion pressure in 22 patients undergoing nonthoracotomy defibrillator implantation. Ventricular fibrillation (VF)/polymorphic ventricular tachycardia (PVT), defined by an irregular limb lead I morphology, was present in 156 dysrhythmia episodes. Monomorphic ventricular tachycardia (VT), present in the remaining 15 episodes, was associated with regular limb lead morphology. All episodes were examined for MAP cycle length, variation, fractionation, and repolarization. VF/PVT cycle length was 215 +/- 28 msec, with a 14 +/- 7% (33 +/- 20-msec) cycle length variability. Nonfractionated MAP recordings were found in 122 of 156 VF/PVT episodes. Episodes characterized as VF by ECG criteria (n = 136) showed lack of MAP diastole and had a mean cycle length of 213 +/- 27 msec. Episodes characterized as PVT (n = 20) were associated with amiodarone therapy and had occasional MAP diastole and a significantly longer mean cycle length of 257 +/- 22 msec (p < 0.001). Monomorphic VT had a mean cycle length of 261 +/- 29 msec, minimal cycle length variation (1 +/- 3%), absence of MAP fractionation, and consistent degree of repolarization before restimulation. CONCLUSIONS: These results suggest that human VF cycle length is limited by cellular refractory periods so that defibrillating shocks interact with cells primarily during their refractory period. PMID- 8504504 TI - Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. AB - BACKGROUND: Increased blood and plasma viscosity, hematocrit, fibrinogen, and activation of coagulation and leukocytes have been reported in patients with claudication; however, their associations with symptomatic and asymptomatic peripheral arterial disease have not been reported in an epidemiological study. METHODS AND RESULTS: Blood and plasma viscosity, hematocrit, fibrinogen, urinary fibrinopeptide A, plasma leukocyte elastase, and uric acid were measured in a random sample of 1,581 men and women aged 55-74 years in Edinburgh, Scotland, and related to peripheral arterial stenosis (ankle-brachial systolic pressure index, ABPI) and to lower limb ischemia (intermittent claudication and reactive hyperemia test). Each variable (except fibrinopeptide A) was significantly related to prevalent symptomatic and asymptomatic peripheral arterial disease. On multivariate analysis, blood viscosity (p < 0.05) and fibrinogen (p < 0.01) were independently associated with peripheral arterial narrowing (ABPI); a positive interaction was found between fibrinogen and smoking in the association with ABPI. Plasma viscosity was associated with claudication in the presence of a given degree of arterial narrowing (odds ratio of claudication in top quintile compared with bottom quintile of plasma viscosity, 3.35; 95% CI, 1.32, 8.51). Leukocyte elastase and uric acid were each associated with reactive hyperemia independently of arterial narrowing (p < 0.01). CONCLUSIONS: Blood rheological factors and leukocyte activation as well as arterial narrowing are associated with lower limb ischemia in the general population and may be implicated in its pathogenesis. PMID- 8504505 TI - Increased left ventricular mass after thoracotomy and pericardiotomy. A role for relief of pericardial constraint? AB - BACKGROUND: Myocardial stretch and increased ventricular filling can lead to increased rates of myocardial protein synthesis. In animal studies, left ventricular mass increases after pericardiectomy, suggesting relief of a biologically meaningful restraining role and a resultant stimulus for growth. The present study was designed to test the hypothesis that combined thoracotomy and pericardiotomy leads to left ventricular hypertrophy in patients with normal left ventricular ejection fraction undergoing elective bypass surgery. METHODS AND RESULTS: Twenty-five patients with normal left ventricular ejection fraction without active myocardial ischemia underwent Doppler and quantitative two dimensional echocardiography 1 day before and 6 weeks and 7 months after elective coronary artery bypass surgery. The pericardium was left widely incised in all patients. Left ventricular end-systolic volume, end-diastolic volume, stroke volume, ejection fraction, end-systolic circumferential wall stress, and mass were measured. Left ventricular end-diastolic volume index increased from 51 +/- 11 mL/m2 to 62 +/- 14 mL/m2 (p < 0.05) at 6 weeks and to 66 +/- 14 mL/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. Left ventricular mass index increased from 109 +/- 23 g/m2 to 127 +/- 24 g/m2 (p < 0.05) at 6 weeks and to 131 +/- 23 g/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. There were no changes in systolic or diastolic blood pressures, end-systolic circumferential wall stress, or end-systolic volume. CONCLUSIONS: Patients with normal left ventricular ejection fraction develop increases in left ventricular end-diastolic volume and mass after coronary artery bypass surgery. These findings support the hypothesis that the increase in left ventricular end diastolic volume associated with thoracotomy and pericardiotomy leads to myocardial growth and an increase in left ventricular mass. PMID- 8504506 TI - Silent ischemia in unstable angina is related to an altered cardiac norepinephrine handling. AB - BACKGROUND: Inferential evidence suggests that silent ischemia might be related to sympathetic activity. Study of [3H]norepinephrine kinetics is a suitable tool to assess the regional sympathetic activity. This method was applied to investigate whether silent myocardial ischemia in unstable angina is related to and depends on cardiac sympathetic overactivity. METHODS AND RESULTS: Patients with active unstable angina were compared with patients with inactive unstable angina, stable effort angina, and controls. Silent myocardial ischemia was evaluated by three 24-hour Holter monitoring periods on alternate days, and [3H]norepinephrine kinetics was assessed under rest conditions and following the cold pressor test. Simultaneously, catecholamine concentrations were measured in the aortic, coronary sinus, and peripheral venous blood. Different than the other groups (p = 0.0013), in patients with active unstable angina, the majority of silent ischemic episodes occurred without increase in heart rate. These patients had a positive coronary sinus-aorta norepinephrine gradient, both at rest and following the cold pressor test. [3H]Norepinephrine kinetics demonstrated an increased selective cardiac spillover, both at rest and, even more, after the cold pressor test. Reduced cardiac [3H]norepinephrine extraction also was found. A significant relation was found between the number of ischemic episodes or the overall duration of silent ischemia and norepinephrine spillover, both at rest and following cold application. CONCLUSIONS: During the acute phase of unstable angina (but not in the quiescent phase or in stable effort angina), a disorder in cardiac norepinephrine handling occurs. This results in a reflex cardiac sympathetic overactivity that plays a major role in the occurrence of silent myocardial ischemia. PMID- 8504507 TI - Comparison of coronary angiographic findings in acute and chronic first presentation of ischemic heart disease. AB - BACKGROUND: It is generally assumed that the clinical manifestations of ischemic heart disease occur randomly on the same underlying pathological process. Therefore, coronary angiographic findings should be similar whether the first presentation of ischemic heart disease is acute myocardial infarction or uncomplicated chronic stable angina. METHODS AND RESULTS: We studied 102 patients (men < or = 60 years old, women < or = 65 years old) presenting with either acute myocardial infarction as first manifestation of coronary artery disease with a concomitant coronary angiogram (55 patients; mean age, 50.2 years) or stable angina for at least 2 years with no history, ECG, or left ventriculographic evidence of any acute event and with an angiogram performed at least 2 years after initial symptoms (47 patients; mean age at symptom onset, 51.7 years). These angiograms were evaluated blindly for severity (number of vessels diseased, stenoses > or = 50%, occlusions), extent of disease (with an index derived by assigning a score of 0-3 per segment, depending on the proportion of lumen length irregularity and dividing the sum by the number of visualized segments), and pattern (discrete: three or fewer loci of disease never involving more than 50% of the length of any segment or diffuse: anything exceeding this). Patients with unheralded myocardial infarction had fewer vessels diseased, fewer stenoses and occlusion, and a lower extent index than those with uncomplicated stable angina (mean +/- SD of 1.3 +/- 0.8 versus 2.1 +/- 0.8, p < 0.001; 2.1 +/- 1.8 versus 3.9 +/- 1.8, p < 0.001; 0.6 +/- 0.6 versus 1.0 +/- 0.9, p < 0.02; and 0.6 +/- 0.5 versus 1.2 +/- 0.5, p < 0.001, respectively). A discrete pattern was present in 54.5% of patients with unheralded infarction and in only 8.5% of those with uncomplicated angina (p < 0.001). CONCLUSIONS: These very different angiographic findings suggest that unheralded acute myocardial infarction and uncomplicated chronic stable angina do not occur randomly on a common atherosclerotic background but rather that additional factors, such as a varying propensity to thrombosis, may predispose to one or the other of these two clinical syndromes. PMID- 8504509 TI - Risk of stroke in adults with cyanotic congenital heart disease. AB - BACKGROUND: Adults with cyanotic congenital heart disease and elevated hematocrit levels are often phlebotomized because of an assumed risk of cerebral arterial thrombotic stroke. Whether a relation exists between hematocrit level, symptomatic erythrocytosis (hyperviscosity), and stroke remains to be established in this patient population. METHODS AND RESULTS: Accordingly, 112 cyanotic patients 19-74 years old (mean, 36 +/- 11.7 years) in the UCLA Adult Congenital Heart Disease Center Registry were selected for study by virtue of continuous observation for 1-12 years (total, 748 patient-years). Patients with independent risk factors for embolic or vasospastic stroke were excluded. The study patients were then divided into two groups: 1) compensated erythrocytosis (stable hematocrit levels of 46.0-72.7% [mean, 57.5 +/- 7.2%], iron replete, absent or mild hyperviscosity symptoms), and 2) decompensated erythrocytosis (unstable rising hematocrit levels of 61.5-75.0% [mean, 69.5 +/- 10.6%], iron deficiency, marked-to-severe hyperviscosity symptoms). No patient with either compensated or decompensated erythrocytosis, irrespective of hematocrit level, iron stores, or the presence, degree, or recurrence of cerebral hyperviscosity symptoms, progressed to clinical evidence of a complete stroke (cerebral arterial thrombosis with brain infarction). CONCLUSIONS: Because a risk of stroke caused by cerebral arterial thrombosis was not demonstrated, because the circulatory effects of phlebotomy are transient, and because of the untoward sequelae of phlebotomy-induced iron deficiency, we recommend phlebotomy for the temporary relief of significant, intrusive hyperviscosity symptoms but not for the hematocrit level per se. According to our data, phlebotomy is not warranted to reduce an assumed risk of stroke because that risk did not materialize. PMID- 8504508 TI - A communitywide perspective of sex differences and temporal trends in the incidence and survival rates after acute myocardial infarction and out-of hospital deaths caused by coronary heart disease. AB - BACKGROUND: The purpose of the study was to examine overall differences and temporal trends therein between men and women regarding the incidence rates, in hospital and long-term survival after initial acute myocardial infarction (AMI), and out-of-hospital deaths caused by coronary disease. METHODS AND RESULTS: This nonconcurrent prospective study was carried out in 16 teaching and community hospitals in Worcester, Mass., in six time periods between 1975 and 1988. A total of 3,148 patients hospitalized with validated initial AMI comprised the study sample. The age-adjusted incidence rates of initial AMI increased between 1975 and 1981 in the two sexes, with a marked decrease thereafter; these rates declined by 26% in men and by 22% in women between 1975 and 1988. The overall unadjusted in-hospital case-fatality rates after initial AMI were significantly higher in women (21.7%) than in men (12.7%). Age- and multivariable-adjusted in hospital case-fatality rates, however, were not significantly different for men compared with women (multivariate-adjusted OR, 0.90; 95% CI, 0.70, 1.16). No clear trends in in-hospital case-fatality rates were observed in men or women over the periods under study. There were no significant sex differences in the age-adjusted long-term survival rates of discharged hospital survivors of AMI. The multivariate-adjusted risk of total mortality among discharged hospital survivors, however, was significantly increased in men (multivariate-adjusted OR, 1.20; 95% CI, 1.03, 1.39); neither of the sexes experienced an improvement over time in long-term prognosis. The incidence rates of out-of-hospital deaths caused by coronary disease declined by 60% in men and 69% in women between 1975 and 1988. CONCLUSIONS: The results of this multihospital, community-based study suggest declines in the incidence rates of AMI and out-of-hospital deaths caused by coronary disease in men and women over the period under study (1975-1988). No significant sex differences in in-hospital survival were observed, whereas a poorer long-term survival experience after hospital discharge was observed for men compared with women after controlling for potentially confounding prognostic factors. PMID- 8504510 TI - Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease. AB - BACKGROUND: Intimal thickenings of the coronary arteries of newborn children are composed mainly of smooth muscle cell proliferations. To investigate whether thickening of the intima in infants is associated with a family history of coronary artery disease (CAD), we studied the relation of coronary death of grandparents to intimal thickening of 136 infants. METHODS AND RESULTS: The length of internal elastic lamina of the artery and the areas of arterial layers in cross section were measured, and the arteries were transformed to idealized round circles. Intimal thickening was assessed as the degree of luminal narrowing (ratio of intimal area to the area on the luminal side of the arterial media). Among 136 infants, luminal narrowing varied between 0% and 58%. CAD deaths accounted for 108 of the total 281 deaths among the grandparents of the infants. Family history of CAD (defined as at least one CAD death among the four grandparents) was positive for 77 infants. Family history of CAD was significantly more common in the infants with luminal narrowing of both the left and right coronary arteries compared with the infants with no narrowing in at least one artery (odds ratio adjusted for sex, infection status, and age of infant, 5.69; 95% confidence interval, 1.46-22.2). After adjustment for sex and age, infants with both a positive family history and presence of infection had an increased degree of luminal narrowing compared with infants with a negative family history and no infection. CONCLUSIONS: The association of coronary artery intimal thickening in infancy with family history of CAD suggests that intimal thickening is a morphological manifestation of predisposition to CAD. PMID- 8504511 TI - Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. AB - BACKGROUND: Recent clinical trial data indicate that the use of angiotensin converting enzyme (ACE) inhibitors among patients with left ventricular dysfunction results in reduced rates of coronary thrombosis, a provocative finding that suggests a potential interaction between the renin-angiotensin system and fibrinolytic function. METHODS AND RESULTS: In four normotensive subjects and six hypertensive patients, we investigated whether infusion of angiotensin II (Ang II) affected circulating levels of plasminogen activator inhibitor-1 (PAI-1), the most important physiological inhibitor of tissue-type plasminogen activator (t-PA). Overall, mean levels of PAI-1 antigen increased significantly from 20.1 ng/mL before Ang II infusion to 36.0 ng/mL at the end of Ang II infusion (p = 0.008), whereas no change in PAI-1 was observed for control subjects infused with 5% dextrose (p = 0.46). Among the normotensive subjects for whom graded doses of Ang II were infused at 0, 1, 3, and 10 ng.kg-1.min-1, mean PAI-1 levels increased sequentially from 14.7 ng/mL to 23.0, 26.8, and 33.5 ng/mL, a dose-response relation that, compared with controls, was highly significant (p < 0.001). Among the hypertensive patients for whom a single 45 minute infusion of Ang II was given at a dose of 3 ng.kg-1.min-1, PAI-1 levels increased from 23.7 to 37.7 ng/mL, whereas PAI-1 levels among control subjects infused with 5% dextrose decreased from 16.9 to 10.8 ng/mL (p = 0.04). Finally, when compared with infusion of 5% dextrose solution, infusion of Ang II appeared to have little effect on circulating levels of t-PA antigen. CONCLUSIONS: These in vivo data suggest that infusion of Ang II results in a rapid increase in circulating levels of PAI-1, a finding that may help to explain clinical observations linking the renin-angiotensin system and thrombotic risk. PMID- 8504512 TI - HLA antigens in Turkish race with rheumatic heart disease [see comment]. AB - BACKGROUND: Rheumatic valvular disease has been reported to be associated with HLA antigens. To determine whether genetic factors could be involved in the pathogenesis of rheumatic heart disease (RHD), we analyzed the distribution of HLA-A, HLA-B, and HLA-DR antigens in Turkish patients with chronic rheumatic heart disease. METHODS AND RESULTS: The association of class I and class II HLA antigens was examined in 107 ethnic Turkish patients with chronic RHD. The diagnosis was supported by echocardiography, cardiac catheterization, angioventriculography, and histological findings in patients who underwent valve replacement. Two hundred three control subjects, also of Turkish origin, were chosen. The phenotypes B16, DR3, and DR7 were encountered in a significantly higher frequency in patients with RHD compared with the control population (corrected p < 0.05, p < 0.00005, and p < 0.0005, respectively). There also was a decrease in the antigen frequency of DR5 in patients compared with controls (corrected p < 0.005). CONCLUSIONS: The results are consistent with the hypothesis that susceptibility to RHD is genetically linked, and this in turn may be associated mainly with HLA class II antigens and weakly with class I antigens, with DR3, DR7, and B16 influencing susceptibility and DR5 conferring protection. PMID- 8504513 TI - Specific IK1 blockade: a new antiarrhythmic mechanism? Effect of RP58866 on ventricular arrhythmias in rat, rabbit, and primate. AB - BACKGROUND: The effectiveness of blockade of the inwardly rectifying K+ current (IK1) in prevention of arrhythmias is unknown. We have examined the antiarrhythmic potential of a new selective IK1 blocker, RP58866, in rat, rabbit, and primate (marmoset) isolated hearts in the settings of acute ischemia and reperfusion. METHODS AND RESULTS: In concentration-response studies (n = 12 per group), the drug reduced ischemia-induced ventricular fibrillation (VF) in rat from control incidence of 100 to 50%, 17% (p < 0.05), and 0% (p < 0.05) at 1, 3, and 10 mumol/L, respectively. RP58866 produced significant bradycardia at the 3- and 10-mumol/L concentrations and significant QT interval widening at all three concentrations (p < 0.05). When rat hearts (n = 12 per group) were paced (5 Hz) via the left atrium to prevent bradycardia, the antiarrhythmic effects of 10 mumol/L RP58866 were unmodified (ischemia-induced VF incidence was reduced by drug from 83% in control hearts to 8%; p < 0.05). Similarly, pacing did not prevent the drug's QT-widening activity at 90% repolarization (QT90 was 64 +/- 3 msec in control hearts versus 128 +/- 17 msec in the presence of 10 mumol/L of drug after 10 minutes of ischemia; p < 0.05). These values are similar to equivalent values in unpaced hearts (65 +/- 3 msec in control hearts versus 159 +/- 15 msec with 10 mumol/L of drug; p < 0.05). In separate groups of rat hearts (n = 10 per group) subjected to 10 minutes of ischemia, reperfusion-induced VF incidence was reduced from 90% in control hearts to 10% (p < 0.05), 0% (p < 0.05), and 0% (p < 0.05) by 1-, 3-, and 10-mumol/L RP58866. To examine whether drug actions were species-specific, we performed further studies in rabbit and primate using the middle concentration of RP58866 (3 mumol/L). Ischemia-induced VF incidence was too low in these species to assess the effects of the drug. However, RP58866 widened QT interval (p < 0.05), slowed heart rate (p < 0.05), and reduced the incidence of reperfusion-induced VF from 67% to 8% (p < 0.05) in rabbit. Furthermore, in the more clinically relevant primate species (marmoset; n = 9-12 per group), RP58866 (3 mumol/L) abolished ischemia-induced VT (36% incidence in control hearts; p < 0.05) and significantly reduced the incidence of ischemia-induced ventricular premature beats from 91% to 33% (p < 0.05). The drug was also effective against reperfusion VF in primates (incidence reduced from 64% in control hearts to 11%; p < 0.05). As in rat and rabbit, RP58866 significantly widened QT interval in primate and caused bradycardia before and during ischemia. RP58866 had no significant influence on coronary flow in any species. Finally, in further studies on rat, QT widening by RP58866 was found to persist relatively unmodified in nonischemic hearts perfused with solution containing K+ elevated to 8 mmol/L to mimic the early ischemic milieu. CONCLUSIONS: RP58866, a selective IK1 blocker, is a potent and efficacious new antiarrhythmic drug in ischemia and reperfusion in rat, rabbit, and primate. When tested in rat, pharmacological activity was undiminished by cardiac pacing or elevation of extracellular K+. PMID- 8504514 TI - Factors contributing to increased vascular fibrinolytic activity in mongrel dogs. AB - BACKGROUND: Numerous investigators have observed that pulmonary emboli are rapidly lysed in a canine model system. This study was undertaken to delineate the unique mechanism that accounts for the rapid dissolution of pulmonary emboli in mongrel dogs. METHODS AND RESULTS: Canine plasminogen activator (PA) activity (2.6 +/- 1.1 IU/mL acidified platelet-poor plasma [PPP], < 0.3 IU/mL acidified whole blood serum [WBS], mean +/- SD; n = 6) and PA inhibitor activity (6.1 +/- 2.6 U/mL PPP, 35.4 +/- 7.8 U/mL WBS; n = 6) were determined in standard plasminogen-based chromogenic assays. Analysis of canine PPP, WBS, platelet lysates, and primary canine endothelial cell (EC) cultures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography revealed a plasminogen-dependent lytic zone at 45-kd relative molecular mass that was shown to be related to urokinase-type PA (u-PA) by its selective inhibition through amiloride. Analysis of canine platelets on standard 125I fibrin plate assays revealed a net fibrinolytic activity. In a clot lysis assay system, canine platelets were able to stimulate fibrinolysis when layered on the outside of fibrin clots containing autologous PPP. Moreover, net fibrinolytic activity of primary canine pulmonary artery endothelial cells was higher than the activities expressed by canine aortic or carotid artery endothelial cells. CONCLUSIONS: Rapid lysis of pulmonary emboli in mongrel dogs appears to be a result of 1) the high u-PA activity in canine PPP and 2) the predominant association of u-PA activity with canine platelets and canine pulmonary artery endothelial cells. PMID- 8504515 TI - Effect of disrupting the mitral apparatus on left ventricular function in dogs. AB - BACKGROUND: The importance of the mitral apparatus to left ventricular function has been suggested in clinical studies. The effect of disruption of the mitral apparatus on left ventricular diastolic and systolic properties has not been fully documented. METHODS AND RESULTS: We investigated the end-diastolic and end systolic pressure-volume and stroke work-end-diastolic volume relations and measured the isovolumic relaxation time constant (tau infinity) during nonfilling beats before and after disruption of the mitral apparatus under different loading conditions in 14 dogs using our recently developed volume-clamping technique for the in situ left ventricle. Disruption of the mitral apparatus increased left ventricular diastolic equilibrium volume (V0d) without changing the slope of the end-diastolic pressure-volume relation (Sd) and increased end-systolic pressure volume relation dead volume (V0s) and volume-axis intercept of stroke work-end diastolic volume relation (V0sw) without changing the slopes of these relations (maximum elastance, Ees, and Ssw). Disruption of the mitral apparatus increased tau infinity. CONCLUSION: Disruption of the mitral apparatus increases the equilibrium volume without changing left ventricular diastolic stiffness or contractility and slows left ventricular relaxation. These results support and help explain the clinical observation that it is desirable to maintain the mitral apparatus during mitral valve replacement surgery. PMID- 8504516 TI - Cardiorenal and neurohumoral function in a canine model of early left ventricular dysfunction. AB - BACKGROUND: Recent studies have reported that asymptomatic left ventricular dysfunction (ALVD) in humans is characterized by early neurohumoral activation. Specifically, atrial natriuretic factor (ANF) and norepinephrine are activated without activation of the renin-angiotensin-aldosterone system (RAAS). The current study describes hemodynamic and renal function associated with this neurohumoral profile in a canine model of early and presumably "asymptomatic" ventricular dysfunction. We hypothesized that the neurohumoral profile observed in ALVD is associated with preservation of renal function despite significant hemodynamic compromise. METHODS AND RESULTS: ALVD was produced by ventricular pacing at 180 beats per minute for 10 days. Intravascular volume expansion was performed before and after producing ALVD in eight conscious dogs. The model of ALVD was characterized by decreases in ejection fraction (48 +/- 2 to 29 +/- 4%), cardiac output (4.64 +/- 0.29 to 2.89 +/- 0.17 L/min), and mean arterial pressure (119 +/- 4 to 108 +/- 4 mm Hg). Atrial pressures and systemic vascular resistance were increased. ANF (60 +/- 19 to 165 +/- 27 pg/mL) and norepinephrine (382 +/- 127 to 690 +/- 211 pg/mL) were activated, whereas the RAAS was not. Creatinine clearance and sodium excretion (UNa V) were unchanged after producing ALVD. The natriuretic response to volume expansion in ALVD was completely intact, with increases in UNa V similar to that observed with volume expansion in ALVD was completely intact, with increases in UNa V similar to that observed with volume expansion before producing ALVD. CONCLUSIONS: The current study demonstrates that significant ventricular dysfunction with peripheral vasoconstriction can be associated with normal renal function and thus suggests an important functional role for the neurohumoral profile of ALVD in preserving sodium balance. PMID- 8504517 TI - Induction of HSP70 in cultured rat neonatal cardiomyocytes by hypoxia and metabolic stress. AB - BACKGROUND: A cultured neonatal rat cardiomyocyte model is used to investigate the expression of the inducible heat shock protein 70 (HSP70i) during hypoxia/reoxygenation and metabolic stress. METHODS AND RESULTS: The major HSP70i is increased in its expression at the mRNA and protein level in myocytes exposed to hypoxia/reoxygenation and metabolic stress by the addition of 2-deoxyglucose and sodium cyanide, which are inhibitors known to block ATP production. Surprisingly, the appearance of HSP70 mRNA precedes the intracellular ATP depletion caused by hypoxia, which is contrary to what we observe when the cardiomyocytes are subjected to metabolic stress. CONCLUSIONS: It has been postulated recently that the decrease in intracellular ATP content in cells under stress may be the trigger that leads to the induction of HSP70i by reducing the pool of free HSP70, thus activating the stress response. Our results indicate that although this may be the case during metabolic stress, another route of activation must be used during the early stages of hypoxia in cardiomyocytes. The induction of HSP70i also appears to precede the onset of cellular damage as measured by the release of cytoplasmic enzymes and preincorporated arachidonic acid. This indicates that cardiomyocytes are able to respond to hypoxia/reoxygenation and metabolic stress with increased HSP70i production and points to a potential protective role of heat shock proteins during ischemia/reperfusion injury. PMID- 8504518 TI - 99mTc-sestamibi uptake and retention during myocardial ischemia and reperfusion. AB - BACKGROUND: 99mTc-methoxyisobutyl isonitrile (Sestamibi) is a new perfusion agent that has shown promise for the noninvasive detection of myocardial salvage after coronary reperfusion in acute myocardial infarction. The objective of this study was to further validate that myocardial uptake and retention of Sestamibi after reperfusion in a canine myocardial infarction model are markers of tissue viability. The hypotheses tested were that if Sestamibi is given early after reperfusion and myocardial uptake is quantitated soon afterward, the degree of ultimate myocardial salvage will be overestimated, and that there will be continued loss of myocardial Sestamibi from ischemic tissue during 3 hours of reperfusion due to accelerated release of Sestamibi from cells already irreversibly injured during the phase of coronary occlusion, reperfusion injury to myocytes still viable early after reflow, or a combination of both mechanisms. METHODS AND RESULTS: In protocol 1, 8.0 mCi Sestamibi was injected intravenously in anesthetized dogs 2-5 minutes after reperfusion preceded by 3 hours of left anterior descending coronary artery (LAD) occlusion. Animals were killed either 5 minutes (n = 7) or 3 hours (n = 9) after Sestamibi administration. Mean endocardial Sestamibi activity was 74 +/- 3% of nonischemic activity in dogs killed early and 31 +/- 2% of nonischemic activity in dogs killed late after Sestamibi administration, indicating myocardial loss of Sestamibi during 3 hours of reflow. Regional flow (percent nonischemic) at the time of Sestamibi administration (2-5 minutes after reperfusion) was comparable in dogs killed early (144 +/- 23%) and dogs killed late (118 +/- 4%, p = NS). In protocol 2, Sestamibi was given intravenously at baseline under normal conditions followed by 3 hours of LAD occlusion and either 4 (n = 6), 30 (n = 9), or 180 minutes (n = 10) of reperfusion. At postmortem, myocardial slices were imaged for quantification of defect magnitude and regional flow (radiolabeled microspheres), and tissue Sestamibi activities were determined by gamma well counting. Coronary sinus Sestamibi activity was serially measured. In these dogs, which were preloaded with Sestamibi at baseline, 3 hours of LAD occlusion followed by 3 hours of reperfusion resulted in a loss of Sestamibi in the endocardial zone of the ischemic region to 40 +/- 6% of nonischemic levels (p < 0.0001). This loss corresponded to a sustained elevation of coronary sinus activity throughout the reflow period. The loss of myocardial Sestamibi was significantly greater than that observed in dogs killed 4 or 30 minutes after reflow. Defect magnitude also worsened over 3 hours of reperfusion as assessed by gamma camera imaging of slices of the excised hearts. CONCLUSIONS: These experimental data suggest that Sestamibi uptake and retention are dependent on myocardial viability as well as regional flow. If Sestamibi is administered early after reperfusion and imaging is performed soon afterward, the degree of myocardial salvage could be significantly overestimated. PMID- 8504519 TI - Intravenous magnesium in acute myocardial infarction. An effective, safe, simple, and inexpensive intervention. PMID- 8504520 TI - The structure of cardiological revolutions. James B. Herrick Lecture. AB - Four revolutions are transforming the cardiology of our day. The first is a social revolution. It has resulted in plummeting esteem for the medical profession reflecting disenchantment coupled with the rapid emergence of the recognition that health care is a right rather than a privilege. The second revolution, interventional cardiology, has provided powerful therapeutic tools demanding technical as well as cognitive expertise. The third, the revolution in molecular and cellular biology, is transforming our understanding of mechanisms underlying disease. Because of the seminal importance of progress in basic science to advances in clinical cardiology, features of these three revolutions are being synthesized in a fourth, a revolution transforming cardiology itself. Novel approaches are needed for optimal training of clinicians with diverse areas of interest, investigators in fundamental and clinical research, house staff, and students; for optimal use of clinical and research resources; and for optimal responsiveness to the needs of patients. They must be developed with cognizance of and fidelity to our clinical and scientific heritage. PMID- 8504521 TI - Angiographic monitoring of reperfusion therapy for acute myocardial infarction. TIMI grade 3 perfusion is the goal. PMID- 8504522 TI - HLA, autoimmunity, and rheumatic heart disease. Apparent or real associations? PMID- 8504523 TI - High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. PMID- 8504524 TI - High stored iron levels. PMID- 8504525 TI - Iron and ischemic heart disease. PMID- 8504526 TI - Predicting torsade de pointes. PMID- 8504527 TI - Declining incidence of ventricular fibrillation in myocardial infarction. PMID- 8504528 TI - Potential value of ultrafast computed tomography to screen for coronary artery disease. Committee on Advanced Cardiac Imaging and Technology, Council on Clinical Cardiology, and Committee on Newer Imaging Modalities, Council on Cardiovascular Radiology, American Heart Association. PMID- 8504529 TI - Candidate reference methods for determining target values for cholesterol, creatinine, uric acid, and glucose in external quality assessment and internal accuracy control. II. Method transfer. AB - We describe the testing of transferability of candidate Reference Methods developed by INSTAND for cholesterol, creatinine, uric acid, and glucose. The methods are based on isotope dilution-gas chromatography--mass spectrometry. The study consisted of two parts: setup of the methods and self-evaluation for readiness in the collaborating laboratory, followed by independent measurements in parallel with INSTAND. Criteria used for judging the transferability and general reliability of the candidate Reference Methods were: the accuracy and precision of the collaborating laboratory and the agreement between the two laboratories. The accuracy was judged from the results on the Standard Reference Material 909 from the National Institute of Standards and Technology. For all analytes except glucose the bias from the certified value was < 0.7%. The mean intralaboratory imprecision ranged from 0.66% to 1.24%. The agreement between the results was tested by an advanced linear-regression analysis and Student's t test. In general, the results demonstrate that the candidate Reference Methods developed by INSTAND can be successfully transferred without loss of their inherent precision and accuracy. PMID- 8504530 TI - Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values. AB - To obtain the best estimates of the average intraindividual biological variability (CVb) in the concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglyceride serum lipids in a person's blood, we evaluated results from 30 studies published from 1970 to 1992. The usually more applicable random-effects model estimated an average CVb of 6.1% for TC, 7.4% for HDLC, 9.5% for LDLC, and 22.6% for triglyceride. Composite estimates of the average CVb from all evaluated published studies by different models of estimation ranged from 6.0% to 6.4% for TC, from 6.2% to 7.5% for HDLC, from 7.0% to 9.6% for LDLC, and from 22.4% to 22.9% for triglyceride. Two important factors influenced the reported biological variation of the study subjects: (a) the magnitude of the variability of the analytical method used and (b) the design characteristics of the study--primarily the number of subjects, the sampling interval, and the number of measurements per subject. For TC, we found a statistically significant positive correlation between the reported mean CVb and both the number of study subjects and the analytical variation. For TC and LDLC we estimate CVb as a function of the study design features. The number of patient specimens required to obtain reliable estimates for serum lipid concentrations are determined from the CVb and the current analytical variation. PMID- 8504531 TI - Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients. AB - Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation. PMID- 8504532 TI - Evaluation of colorectal cancer-associated mucin CA M43 assay in serum. AB - The technical performance of a newly developed assay for CA M43, a serum marker for colorectal cancer, was evaluated and its preliminary clinical potential assessed. The heterologous double-determinant enzyme immunoassay for the detection of the tumor-associated mucin CA M43 utilizes two monoclonal antibodies (CT 43 and CT 66) selected for their binding capacity to two distinct epitopes present on mucins in the sera of patients with colorectal cancer. CT 66 recognizes both Lewis(a) and sialylated Lewis(a) antigen; CT 43 is directed toward a mucin epitope of an as-yet uncharacterized structure. Precision experiments revealed interassay CVs of 11.8%, 5.9%, and 4.9% at 9.3, 11.9, and 78.9 units/mL, respectively; intraassay precision was 2.0% at 95.1 units/mL. The upper normal value was set at 7.5 units/mL, which included 99% of the values found in healthy controls. In colorectal cancer patients, CA M43 showed a positivity rate equivalent to that of carcinoembryonic antigen (CEA) and superior to that of CA 19.9, with only one CA 19.9-positive serum being negative for CA M43. Interestingly, CA M43 appeared to be complementary to CEA, with CA M43 and CEA together reaching 87% positivity in metastatic disease. PMID- 8504533 TI - Dipyrone interference on several common biochemical tests. AB - We studied the effect in vitro and in vivo of dipyrone on the determination of several biochemical tests in two analyzers, a Hitachi 747 and a Kodak Ektachem 700. From studies in vitro, we found significant interference by dipyrone (P < 0.05) in the determination of creatine kinase (CK), lactate dehydrogenase (LD), uric acid, triglycerides, cholesterol, aspartate aminotransferase, alanine aminotransferase, and urea nitrogen with both instruments, and in the determination of creatinine in the Ektachem analyzer. We also studied the effect of intravenously administered dipyrone in 14 patients. Dipyrone interfered significantly (P < 0.05) in the determination of CK, LD, uric acid, triglycerides, and cholesterol with both instruments, and creatinine only with the Ektachem analyzer. Using high-performance liquid chromatography (HPLC), we measured concentrations of dipyrone in the serum of patients who had received the drug and observed a negative correlation between the concentrations of dipyrone in the blood and the percentage of each analyte concentration. PMID- 8504534 TI - Determination of trace elements in blood serum of patients with Behcet disease by total reflection x-ray fluorescence analysis. AB - The distribution of trace elements Fe, Cu, Zn, Se, and Rb was determined in sera from patients with the complete type of Behcet disease in the active stage and from healthy controls. Total reflection x-ray fluorescence was used for quantitative analysis; in general, atomic absorption spectrometry was used only for control of the Se values. Zn, Se, and Rb concentrations were significantly (P < 0.0001) lower for patients than for control subjects. No significant difference was determined in the Fe content. However, there was a significant increase in Cu in the patients so that the ratios Cu/Zn, Cu/Se, and Cu/Rb were significantly higher for the patients than for the control subjects (P < 0.0001). PMID- 8504535 TI - Reference intervals for 21 clinical chemistry analytes in arterial and venous umbilical cord blood. AB - Reference intervals were determined for 21 clinical chemistry analytes in umbilical cord arterial and venous blood from healthy term infants. Nonparametric analysis (rank number) was used to determine the central 95% reference interval. No significant differences were observed between male and female infants. Reference intervals for glucose, urea, creatinine, urate, phosphate, calcium, albumin, total protein, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, and magnesium all were significantly different from adult values. PMID- 8504536 TI - Comparison of cyclosporin G (Nva2-cyclosporin) concentrations measured in whole blood by monoclonal fluorescence polarization immunoassay, monoclonal radioimmunoassay, and HPLC. AB - Two commercial monoclonal immunoassays for monitoring cyclosporin A were used to measure whole-blood concentrations of the immunosuppressant cyclosporin G (CsG) in renal transplant patients. We performed a three-way comparison of these two immunoassays and HPLC. Although the two immunoassays agreed favorably, both the monoclonal fluorescence polarization immunoassay and the monoclonal RIA yielded higher CsG results for patients' specimens than did the liquid-chromatographic assay. The experimental data indicate that the observed differences are most likely due to the cross-reactivity of CsG metabolites in the immunoassays. PMID- 8504537 TI - The freckle plot (daily turnaround time chart): a technique for timely and effective quality improvement of test turnaround times. AB - Test turnaround times are often monitored on a monthly basis. However, such an interval usually means that not all causes for delay in test reporting can be unequivocally identified for institution of remedial action. We have devised a daily chart--the freckle plot--that graphically displays the test turnaround times by laboratory receipt time. Different symbols are used to designate specimens reported within the test's turnaround time limit, those within 10 min beyond that limit, and those well outside the limit. These categories are adjustable to suit different limits of stringency. Freckle plots are produced on a daily basis and can be used to track down causes for test delays. Using the 1-h turnaround time "stat" potassium test as a model, we found 16 causes for test delay, of which 9 were potentially remediable. By applying these remedies, we were able to increase test compliance, in the day shift, from 91.5% (95% confidence interval 88.8%-93.7%) to 97.6% (95% confidence interval 96.4-98.55%), which is significant at P < 10(-7). This daily plot is a useful quality assurance tool, supplementing the more conventional tests used to ensure laboratory quality improvement. PMID- 8504538 TI - Glutamine stability in biological tissues evaluated by fluorometric analysis. AB - Although glutamine has been considered unstable during storage and therefore difficult to quantitate, recent results suggest this amino acid is stable at low pH ranges. We evaluated the stability of glutamine in plasma and tissue extracts, using fluorometric analysis. The measured concentration of glutamine detected varied linearly up to 0.8 mmol/L for the aqueous solution (r2 = 98.7, P = 0.0001) with a mean (+/- SD) coefficient of variation of 2.41% +/- 0.79%. When glutamine was dissolved in 50 g/L trichloroacetic acid (TCA), the values were essentially unaltered. Glutamine in an aqueous solution and stored at -70 degrees C was stable for at least 16 days; glutamine in TCA was stable for 6-8 days, then decreased to a concentration significantly lower than that of the aqueous solution. The expected and observed concentrations in plasma were equal (r2 = 0.99975) for increasing amounts of added glutamine. Glutamine concentrations in plasma were stable for > 1 year when stored at -70 degrees C. The glutamine of a transplantable rat sarcoma and a normal rat liver could be extracted with 50 g/L TCA with high efficiency (88.6% +/- 1.9% and 90.2% +/- 0.04%, respectively); the extracted glutamine is stable in TCA for at least 7 days without neutralization when stored at -70 degrees C. Fluorometric analysis of glutamine required only a small quantity of plasma (25 microL) or tissue (200 mg) and is a convenient method for quantifying this important amino acid. PMID- 8504539 TI - Analytical evaluation of i-STAT Portable Clinical Analyzer and use by nonlaboratory health-care professionals. AB - We evaluated the performance of the i-STAT Portable Clinical Analyzer, a hand held instrument that, with its current cartridge, analyzes for electrolytes, urea nitrogen, glucose, and hematocrit in approximately 60 microL of whole blood in approximately 90 s. Accuracy, imprecision, and linearity studies were performed with aqueous controls and standards and by split-sample analysis. Intrarun imprecision (CV) ranged from 0.34% to 3.97%. Total imprecision over a 2-month period ranged from 0.42% to 4.83%, with urea nitrogen and glucose analyses generating the higher values. Patients' results from the Portable Clinical Analyzer correlated well with those obtained for whole blood or plasma by the Nova Stat Profile 5, the Beckman Synchron CX3, or the Technicon H1 Hematology Analyzer, with Sylx values < 0.2 mmol/L for potassium; < 1.5 mmol/L for sodium, glucose, and urea nitrogen; < 2.4 mmol/L for chloride, and < 2.4% for hematocrit. We also ascertained imprecision and accuracy of the system placed in a cardiothoracic intensive-care unit and operated by nurses. There were no significant differences in either the imprecision or accuracy of the system in this setting. We conclude that operator technique is not a factor in the analytical performance of the system and that it can be used by nonlaboratorians with a high degree of confidence that reliable results will be obtained. PMID- 8504540 TI - Reported effects of long-term freezer storage on concentrations of retinol, beta carotene, and alpha-tocopherol in serum or plasma summarized. AB - A literature review of the effects of long-term freezer storage on concentrations of antioxidant micronutrients in serum or plasma showed that a high proportion of the studies that compared the concentrations of retinol, beta-carotene, or alpha tocopherol in fresh and stored serum were deficient because of small numbers of observations, imprecise descriptions of procedures, and short periods of storage. Data from nested case-control studies of the associations of these micronutrients with cancer are confounded by differences in the study populations. Nevertheless, the overall impression is strong that retinol is stable at storage temperatures as warm as -20 degrees C for at least 15 years, that moderate losses of alpha tocopherol occur at temperatures above -40 degrees C during that period, and that only a small proportion of beta-carotene persists at storage temperatures above 40 degrees C. At -70 degrees C or colder, all three micronutrients appear to be stable for at least 15 years. PMID- 8504541 TI - Inaccuracy of osmometry for measurement of plasma water in acute diabetes mellitus. AB - Osmometry is reportedly a relatively imprecise technique for the measurement of plasma water. However, reconsideration of the theoretical background of the test reveals that it is also likely to be inaccurate and subject to both positive errors as well as viscosity-dependent negative errors simultaneously, when applied to samples from patients admitted in acute diabetes mellitus. This was confirmed by comparison with Waugh's method of results for 59 specimens from 14 cases. Plasma water was shown to be relatively underestimated at high protein concentrations and overestimated at lower ones. PMID- 8504542 TI - Comparison of hypertonic and isotonic reference electrode junctions for measuring ionized calcium in whole blood: a clinical study. AB - We measured ionized calcium concentrations in whole blood from 91 patients who had no clinical or biochemical evidence of disturbed calcium homeostasis and who had a wide range of serum albumin concentrations. We used both a standard Ciba Corning 634 analyzer, which has a membrane-restricted saturated KCl reference electrode bridge, and a modified instrument with a 150 mmol/L NaCl bridge. After adjusting the externally standardized values from each instrument for their least squares regressions on pH, there was a significant correlation between ionized calcium and albumin only with the standard analyzer. In contrast, only values from the modified instrument correlated with serum chloride; this was not explained by ionic strength or organic anion interferences. We conclude that there is unlikely to be any major advantage in using a membrane-restricted isotonic NaCl reference electrode for in vitro clinical measurements, although it may be of value for in vivo monitoring. The importance of measuring serum albumin when using most commercial ionized calcium analyzers is emphasized. PMID- 8504543 TI - Commercial kits for 1,25-dihydroxyvitamin D compared with a liquid chromatographic assay. AB - Three commercially available kits for 1,25-dihydroxyvitamin D [1,25(OH)2D] determination were compared with a liquid-chromatographic method. Serum samples were analyzed for 1,25(OH)2D from 70 healthy subjects (age 2.2-17.5 years; 35 males, 35 females), some (n = 5) given orally high vitamin D3 doses. In addition, 1,25(OH)2D was measured in 28 patients with untreated diseases associated with low (n = 16) or high (n = 12) serum concentrations of the hormone. The results showed that the commercial kits were sufficiently accurate with respect to the comparison method and suitable for routine clinical work. PMID- 8504544 TI - Cross-reactivities of cyclosporin G (NVa2 cyclosporin) and metabolites in cyclosporin A immunoassays. AB - Immunoassays of cyclosporin A (CsA) have been routinely used to measure CsG. We investigated the cross-reactivities of CsG and its metabolites, as well as the proportion CsG constitutes in relation to total drug measured, for six CsG metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) in the following CsA assays: Sandimmune selective RIA (SS), Sandimmune nonselective RIA (NS), Cyclotrac SP-RIA (CT), fluorescence polarization immunoassay (FPIA), and enzyme immunoassay (EMIT). The cross-reactivity of CsG in these assays was as follows: SS, FPIA, CT, approximately 100%; NS, approximately 40%; EMIT, < 2%. The cross-reactivities of CsG metabolites were investigated in all assays except EMIT and varied among metabolites and assays. The most significant variance was found with the NS assay, where most of the metabolites exhibited cross-reactivities of > 40%. In contrast, in the SS, FPIA, and CT assays, cross-reactivities of < 5% were observed for most of the metabolites. The ranking of cross-reactivities of CsG metabolites in the assays is SS = CT < FPIA < NS. The degree of cross-reactivity did not change significantly when the SS, CT, and FPIA assays were calibrated with CsG instead of CsA--whether parent CsG was present or not. The data suggest that the SS, CT, and FPIA methods would be suitable for the routine monitoring of CsG. PMID- 8504546 TI - Asymptomatic 5-oxoprolinuria detected by proton magnetic resonance spectroscopy. PMID- 8504545 TI - Childhood porphyrias: implications and treatments. AB - In describing the clinical, biochemical, and family findings in five children with porphyria, we examine initial treatments and, where appropriate, the effectiveness of long-term therapy. We note that porphyria diagnosis, particularly in childhood, relies heavily on specialist laboratory investigations. Because disease expression in some porphyrias requires exposure to precipitating factors, it may be prevented or delayed by their avoidance. PMID- 8504547 TI - The free thyroid hormone hypothesis and measurement of free hormones. PMID- 8504548 TI - Ethylbenzene and xylene from Sarstedt Monovette serum gel blood-collection tubes. PMID- 8504549 TI - "High-dose hook effect" with the Centocor CA 125 assay. PMID- 8504550 TI - HPLC determination of caffeine and theophylline by direct serum injection. PMID- 8504551 TI - Whole-blood lead reference intervals for adults. PMID- 8504552 TI - Novel homozygous mutation of phenylalanine hydroxylase gene in a Chinese patient with phenylketonuria. PMID- 8504553 TI - Assessment of high-density lipoprotein cholesterol in hypertriglyceridemic sera. PMID- 8504554 TI - Modification of commercial assay kits is justified. PMID- 8504556 TI - Influence of hematocrit on quantitative analysis of "blood spots" on filter paper. PMID- 8504555 TI - Is salivary cortisol a better index than free cortisol in serum or urine for diagnosis of Cushing syndrome? PMID- 8504558 TI - On P values and confidence intervals (why can't we P with more confidence?) PMID- 8504557 TI - False-positive serum tricyclic antidepressant screen with cyproheptadine. PMID- 8504559 TI - Chemistry with confidence: should Clinical Chemistry require confidence intervals for analytical and other data? AB - Confidence intervals are not commonly provided with analytical or other data reported in Clinical Chemistry although P values are. However, confidence intervals provide an explicit demonstration of the direction and magnitude of uncertainty and are intuitively easy to grasp, unlike P values. It is therefore argued that the Journal should adopt a policy requiring the provision of confidence intervals. Such a policy would improve the statistical rigor of Journal reports. PMID- 8504560 TI - Simultaneous determination of free testosterone and testosterone bound to non-sex hormone-binding globulin by equilibrium dialysis. AB - We describe a procedure based on equilibrium dialysis that allows the simultaneous determination of free testosterone and testosterone bound to non-sex hormone-binding globulin (non-SHBG) in plasma. After saturating SHBG with 5 alpha dihydrotestosterone (DHT) according to a technique recently described, the percentage of free testosterone in the treated and the untreated samples is measured by equilibrium dialysis with use of a semiautomated instrument that allows rigorous standardization of the experimental conditions. The present method is simpler and faster than the previously described technique in which, after the saturation of SHBG with DHT, the unbound fractions were measured by centrifugal ultrafiltration dialysis. The method is also reproducible and suited for the analysis of a large number of samples. The technique has been applied to the determination of the fractional distribution of testosterone in plasma pools from normally menstruating, pregnant, and postmenopausal women and from normal men. PMID- 8504561 TI - Sandwich enzyme immunoassay of osteocalcin in serum with use of an antibody against human osteocalcin. AB - We have developed and thoroughly validated a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) on microtiter plates for osteocalcin in human serum with use of an antibody raised against human osteocalcin. We used a monoclonal antibody against bovine osteocalcin as the capture antibody; the second antibody was a polyclonal antibody against human osteocalcin. The amount of bound second antibody was determined with use of swine anti-rabbit antibody labeled with horseradish peroxidase. We demonstrated independence of volume and determined the recovery of added standard and within- and between-assay precision. The minimal detection limit for osteocalcin was between 1.0 and 1.5 micrograms/L and the midpoint of the standard curve ranged from 14 to 17 micrograms/L. The intraassay CV was < or = 8% in the range 2.7-52 micrograms/L; the interassay CV was usually < or = 15% in the same range. Analytical recovery of human osteocalcin standard added to serum samples was consistently > 90%. Values for osteocalcin measured in serum from 44 normal subjects were similar to those obtained with a competitive enzyme immunoassay (EIA) that used a monoclonal antibody against bovine osteocalcin. There was a good correlation between the two assays [r2 = 0.877, slope and intercept (+/- SE) = 0.88(+/- 0.051) and 0.316(+/- 0.523), respectively]. The range and mean (+/- SD) for the sandwich ELISA and the competitive EIA were 1.7-18.1 micrograms/L [8.7(+/- 4.4) micrograms/L] and 1.9 22.8 micrograms/L [9.1(+/- 4.4) micrograms/L], respectively. PMID- 8504562 TI - Partial least-squares regression for routine analysis of urinary calculus composition with Fourier transform infrared analysis. AB - Quantitative assessment of urinary calculus (renal stone) constituents by infrared analysis (IR) is hampered by the need of expert knowledge for spectrum interpretation. Our laboratory performed a computerized search of several libraries, containing 235 reference spectra from various mixtures with different proportions. Library search was followed by visual interpretation of band intensities for more precise semiquantitative determination of the composition. We tested partial least-squares (PLS) regression for the most frequently occurring compositions of urinary calculi. Using a constrained mixture design, we prepared various samples containing whewellite, weddellite, and carbonate apatite and used these as a calibration set for PLS regression. The value of PLS analysis was investigated by the assay of known artificial mixtures and selected patients' samples for which the semiquantitative compositions were determined by computerized library search followed by visual interpretation. Compared with that method, PLS analysis was superior with respect to accuracy and necessity of expert knowledge. Apart from some practical limitations in data-handling facilities, we believe that PLS regression offers a promising tool for routine quantification, not only for whewellite, weddellite, and carbonate apatite, but also for other compositions of the urinary calculus. PMID- 8504563 TI - Plasma immunoreactive endothelin in the acute and subacute phases of myocardial infarction in patients undergoing fibrinolysis. AB - Endothelin is a potent vasoconstrictor of coronary arteries. We measured plasma concentrations of immunoreactive endothelin (irET) in 46 patients with confirmed acute myocardial infarction (AMI). When compared with irET concentrations in healthy individuals who served as controls, irET concentrations in patients were already significantly elevated at the time of admission (P = 0.002) and remained significantly elevated for at least 2 days after AMI (P < 0.01). IrET concentrations peaked 1 h (mean) after admission (8.5 +/- 3.9 ng/L, P = 0.02 compared with values at time of admission). Reperfusion of the infarct-related artery markedly influenced irET release. Before the start of thrombolytic therapy, irET concentration in patients with early reperfusion did not differ significantly from that of those without early reperfusion. However, irET time courses were significantly (P = 0.03 by analysis of variance) different in patients who did and did not have early reperfusion. In the latter, peak irET concentrations correlated closely with the angiographic left ventricular ejection fraction (r = -0.71, P = 0.03), maximum creatine kinase MB mass concentrations (r = 0.69, P = 0.01), and creatine kinase activities (r = 0.59, P = 0.03). Reflow and reversion of myocardial ischemia are associated with a reduced irET release in patients with AMI. PMID- 8504564 TI - Sequential ultracentrifugation micromethod for separation of serum lipoproteins and assays of lipids, apolipoproteins, and lipoprotein particles. AB - We describe a fast sequential separation of very-low-density, low-density, and high-density lipoproteins from 400 microL of serum, using the Beckman TL100 ultracentrifuge. The cumulative centrifugation time is 9.5 h. The purity of lipoprotein fractions was verified by a gel-filtration procedure. The major contaminant is the serum albumin, which can be eliminated by a second centrifugation at the same density. Enzymatic measurement of lipids shows good recovery (> 91%) and weak within-sample variation (< 7%). In comparison with a density-gradient procedure, the deleterious effects on the lipoprotein structure appear to be limited, as shown by the low concentrations of apolipoprotein (apo) E and apo A-I in the fraction > 1.21 kg/L. Furthermore, the micro ultracentrifugation also gives a better recovery rate. Finally, we have studied the distribution of lipids, apolipoproteins, and lipoprotein particles (LpA-I:A II, LpB:C-III, LpB:E) in each fraction separated from 10 serum samples from healthy subjects. PMID- 8504565 TI - Determination of one thousandth of an attomole (1 zeptomole) of alkaline phosphatase: application in an immunoassay of proinsulin. AB - Enzyme amplification has proved to be a highly sensitive quantification technique for immunoassays. We have shown that by using a fluorescent end-point, even more sensitive enzyme amplification assays can be generated than hitherto reported. We describe some general properties of this system and demonstrate its application in an assay for human proinsulin in plasma. The detection system can be used to measure less than one thousandth of an attomole (1 zeptomole) of alkaline phosphatase, equivalent to about 350 molecules of alkaline phosphatase per well of a microtiter plate. We have used this system to construct a proinsulin assay with a sensitivity of 0.017 pmol/L. PMID- 8504566 TI - Cardiac-specific immunoenzymometric assay of troponin I in the early phase of acute myocardial infarction. AB - The screening by immunoenzymometric assay (IEMA) of 784 monoclonal antibody (MAb) combinations resulted in the selection of an optimal pair of MAbs for measuring human cardiac troponin I (TnI). Using a one-step IEMA described here, we were able to detect TnI within the range of 0.2-20 micrograms/L in 30 min at room temperature. No cross-reactivity was observed with the skeletal isoforms of troponin up to a concentration of 500 micrograms/L. This assay was used to measure cardiac TnI in the plasma of 43 patients with acute myocardial infarction (AMI). TnI was detected relatively early after the onset of chest pain (4.3 +/- 2.1 h, mean +/- SD); the peak occurred after 12.2 +/- 4.6 h in a population that had undergone fibrinolysis. TnI disappearance was generally observed between 5 and 9 days after the onset of chest pain. No cardiac TnI could be detected in 145 healthy donors or in a control group of 6 patients (with skeletal damage or rhabdomyolysis). This assay allows a specific diagnosis of AMI in its early acute phase, with a high diagnostic specificity and sensitivity. PMID- 8504567 TI - Redox status and protein binding of plasma aminothiols during the transient hyperhomocysteinemia that follows homocysteine administration. AB - We administered reduced L-homocysteine perorally (67 mumol/kg of body wt) to 12 healthy subjects and injected the same dose into one person, and determined the kinetics of the alterations in reduced, oxidized, and protein-bound concentrations of homocysteine, cysteine, and cysteinylglycine. After oral intake, reduced homocysteine increased rapidly (tmax < or = 15 min), reaching concentrations [3.97 (SD 2.99) mumol/L] 20-fold above fasting values, and then declined towards the normal concentration within 2 h. There was a similar increase in reduced cysteine and a moderate increase in reduced cysteinylglycine. During this response, we observed a positive correlation between the reduced/total ratio for homocysteine and cysteine. When homocysteine was injected, the increase in reduced homocysteine preceded the increase in reduced cysteine by about 3 min. After oral loading, oxidized homocysteine showed a transient increase (tmax = 30 min) that lagged behind the increase of reduced homocysteine. Oxidized cysteine and cysteinylglycine were stable or decreased slightly. Protein-bound homocysteine increased the least rapidly after homocysteine administration (tmax = 1-2 h), and returned to normal values slowly. Changes in protein-bound homocysteine essentially mirrored a concurrent decrease in protein-bound cysteine, suggesting displacement of bound cysteine. These data show that plasma homocysteine has a pronounced, direct effect on the redox status and protein binding of other plasma thiol components. Such effects should be recognized when studying the mechanisms behind the atherogenic effect of increased plasma homocysteine. PMID- 8504568 TI - Candidate reference methods for determining target values for cholesterol, creatinine, uric acid, and glucose in external quality assessment and internal accuracy control. I. Method setup. AB - In Germany, the target values for External Quality Assessment (EQA) and internal accuracy control are determined by Reference Methods for several analytes, including cholesterol, creatinine, uric acid, and glucose. We present candidate Reference Methods for these compounds, based on isotope dilution-gas chromatography--mass spectrometry methods that have been developed at INSTAND, one of the two official Germany EQA reference institutions. Each Reference Method target value is calculated from six independent measurements performed on three different days. The mean method CVs ranged from 0.66% for glucose to 0.96% for creatinine. The inaccuracy (bias) of the methods is < 0.7%, as compared with the Standard Reference Material 909 of the National Institute of Standards and Technology. The maximum total error of a Reference Method value, including the 95% confidence interval and systematic errors, is < 2.3%. The presented candidate Reference Methods have been successfully used to set target values in the German EQA scheme and the internal accuracy control of routine laboratories. PMID- 8504569 TI - Transseptal left heart catheterization for radiofrequency ablation of accessory pathways. AB - In summary, I think it is important to state that transseptal left heart catheterization is a safe procedure when the operator pays meticulous attention to detail. Potential complications can be avoided if the operator: (1) heparinizes the sheath prior to catheterization, (2) fully heparinizes the patient when the catheter and sheath are across the septum, and (3) remembers that the left atrium in these patients is quite small and can be perforated easily by the tapered tip of the transseptal catheter. Transesophageal cardiac ultrasound makes this latter point very clear to anyone doing this procedure. PMID- 8504570 TI - Endovascular stents: preliminary clinical results and future developments. AB - At present, there is an exponential use of new interventional techniques whose proper role and value have not yet been defined. The intracoronary stent is just one example. There is no doubt that stents can be implanted with a high technical success rate associated with highly predictable immediate angiographic results and that they appear to be superior to all other interventional techniques. However, the intrinsic thrombogenicity of all devices currently available for clinical use warrants a vigorous anticoagulation, exposing the patient either to the risk of (sub)acute stent thrombosis or to the risk of hemorrhage and vascular complications. It remains to be determined whether stent implantation will reduce the incidence of restenosis and whether this results in an improved long-term event and symptom-free survival. Experimental studies indicate that the thrombogenic nature of stents may be controlled by coating the struts with endothelial cells or polymers. With respect to restenosis, it is evident that as long as mechanical injury is applied to the vessel wall, the vessel wall will respond with neointimal thickening. The intracoronary stent has the potential to control this tissue response by serving as a carrier for local antiproliferative drug delivery or eventually for genetic manipulation. The intensive research which is now going on in combination with experimental animal data, human postmortem pathologic observations, and angiographic studies is yielding clear insights and future directions to address these issues. PMID- 8504571 TI - Newer concepts in the medical management of patients with congestive heart failure. AB - Congestive heart failure (CHF) remains a major cause of morbidity and mortality in the United States, especially among the elderly. Although an underlying disturbance in cardiac function can be identified in most patients, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. The renin-angiotensin system (RAS) is integrally involved in the pathophysiology of CHF. Originally considered a humoral system, the RAS is now known to exist and operate within cardiac and vascular tissues. The importance of tissue-specific renin-angiotensin systems in CHF is presently under investigation. Most patients with symptomatic CHF benefit from the administration of an ACE inhibitor. Certain asymptomatic patients, such as those with severe left ventricular (LV) dysfunction and those who are at high risk for LV remodeling after anterior wall myocardial infarction, may also benefit from ACE inhibitor therapy. Diuretics and nitrates improve symptoms and often cardiac output in many patients with CHF. Although many new inotropic agents have been tested in CHF patients, none appear clinically superior to digitalis glycosides. The efficacy of digitalis glycosides in CHF may in part result from sympathoinhibitory properties such as the activation of baroreceptor mechanisms. Despite the fact that many CHF patients die from arrhythmias, treatment of asymptomatic ventricular arrhythmias in these patients is not recommended. Patients with symptomatic or sustained ventricular arrhythmias are best treated by a physician experienced in cardiac electrophysiology. Therapy with beta blocking drugs for CHF patients is controversial. Anticoagulants are recommended for selected patients with CHF. Finally, exercise therapy may improve functional capacity in some patients with CHF through its effects on peripheral blood vessels and skeletal muscle tissues. PMID- 8504572 TI - Long-term growth following neonatal anatomic repair of transposition of the great arteries. AB - Despite generally normal prenatal growth, surviving infants with transposition of the great arteries (TGA) frequently develop severe and progressive growth impairment which is not always fully reversed by elective atrial repair within the first year of life. This study was undertaken to determine the effect of neonatal anatomic repair of TGA on long-term growth. Twenty-three children with uncomplicated TGA were followed for a mean of 60 (12-90) months after anatomic repair at a mean age of 11 (1-40) days. Standardized measurements of weight, height, and head circumference for both patients and normal siblings were expressed as percentiles as well as in Z scores (in standard deviations from the mean for age and sex) based on internationally recognized standards. At latest follow-up, 22 (96%) of the patients were above the 3rd percentile for weight and 21 (91%) for both height and head circumference, with 13 (57%), 11 (48%), and 13 (57%) above the 50th percentile for each respective parameter. The mean Z scores (+/- SD) for weight, height, and head circumference for the patient group were 0.1 +/- 1.2, -0.2 +/- 1.3, and -0.1 +/- 1.1, respectively, and did not differ significantly from those of the reference population (p > 0.05 for each comparison). Paired comparisons of mean Z scores for each growth parameter with those of 35 normal siblings demonstrated no significant difference for weight or height and a small but significant difference for head circumference. Age at surgical repair (within the first 6 weeks of life), duration of follow-up and the development of moderate supravalvar pulmonary stenosis were not statistically related to long-term growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504573 TI - One-year prognosis in patients hospitalized with a history of unstable angina pectoris. AB - The prognosis during 1 year of follow-up in 715 patients admitted to one single hospital due to suspected acute myocardial infarction (AMI) with a history of unstable angina pectoris immediately preceding hospitalization is described. AMI developed in 192 patients (27%) during the first three days and in 255 patients (38%) during the first year. The mortality during hospitalization was 7% (50 patients) and during 1 year 19% (130 patients). Of the nonsurvivors, 54% died of AMI, 28% of congestive heart failure, and 20% of cardiogenic shock. Based on simple clinical parameters on admission to the emergency room, risk indicators for death during the following year could be identified as follows, in the order of significance: high age (p < 0.001), ST-segment depression on admission (p < 0.001), and a history of diabetes mellitus (p < 0.05). At admission to the emergency room, risk indicators for development of AMI during the following year were as follows: initial degree of suspicion of AMI (p < 0.001), electrocardiographic signs of acute ischemia on admission (p < 0.001), ST-segment elevation on admission (p < 0.01), age (p < 0.05), and lack of a previous history of chronic stable angina pectoris (p < 0.05). We conclude that, among patients admitted to hospital due to suspected AMI with a history of unstable angina pectoris immediately preceding hospitalization, 38% developed a confirmed infarction and 19% died during the following year. PMID- 8504574 TI - Progression of left ventricular enlargement in patients with hypertrophic cardiomyopathy: incidence and prognostic value. AB - A total of 51 patients with hypertrophic cardiomyopathy (HCM) were followed for at least 3 years (mean follow-up period 6.5 years) by serial M-mode and two dimensional echocardiography. An increase of the left ventricular diastolic dimension (LVDd) to > or = 55 mm with a decrease in the left ventricular ejection fraction (LVEF) to < 55% was observed in eight (15.7%) patients (progressive disease group). In five of these eight patients, the LVDd was > or = 60 mm and the LVEF was < 40%. Ventricular enlargement was closely related to mortality and death due to congestive heart failure occurred in three of these patients. No deaths occurred among the 37 patients without significant progression of ventricular enlargement (nonprogressive group). The annual changes of LVEF and LVDd in the progressive disease group were larger than in the nonprogressive group (LVEF -0.18 +/- 1.45 vs. -2.46 +/- 1.47 %/year; LVDd 0.22 +/- 0.81 vs. 1.43 +/- 0.77 mm/year). An increment in LVDs occurred earlier than the enlargement of the LVDd. Therefore, close attention to the LVDs seems to be important to detect early left ventricular morphological changes in HCM. In summary, this study indicates that HCM patients include a subgroup with symptoms resembling dilated cardiomyopathy, in whom the left ventricle enlarges with hypofunction and in whom there is high mortality due to congestive heart failure. PMID- 8504575 TI - Effects of intravenous SM-9527 (double-chain tissue plasminogen activator) on left ventricular function in the chronic stage of acute myocardial infarction. AB - Clinical effects of thrombolytic agent SM-9527 (double-chain tissue plasminogen activator) on left ventricular (LV) function were assessed in patients with acute myocardial infarction (AMI). A dose of 30 x 10(6) IU SM-9527 was given intravenously to patients with AMI within 6 h after onset. Of 159 candidates, 20 were excluded from the trial due to diseases other than myocardial infarction or failure to meet the protocol requirements; 114 of the remaining 139 were subjected to LV function analysis. The following results were obtained: (1) Patients with successful reperfusion in response to SM-9527 in the acute stage without later reocclusion revealed a significant improvement of LV function in the chronic stage. (2) Adverse effects were noted in 15 patients (10.8%), but none were serious; all were bleeding related to catheterization. (3) Hemagglutination fibrinolysis system test revealed no problems. It is concluded that early thrombolytic therapy with intravenous SM-9527 for AMI provides significant improvement of LV function in the chronic stage. PMID- 8504576 TI - Characteristics of reactive electropermeable points on the auricles of coronary heart disease patients. AB - In oriental medicine there is a hypothesis related to acupuncture that the auricle is a projection of the functional anatomy of the whole human body. In this study reactive electropermeable points (REPP), that is, points on the skin with low electrical resistance, on the auricle were measured on patients with coronary heart disease using a neurometer LC-M. Our findings correlated positively with the particular points--heart I (shin) and heart II (shinzo)*- named by the Chinese group as being related to the functional anatomy of the heart. The incidence of positive REPP test results at the shin and shinzo points for subjects with acute myocardial infarction (AMI) were extremely high, and positive test results for patients with old myocardial infarction (OMI) and angina pectoris (AP) were also significant. There was no significant difference in the incidence rates of REPP at the shin and shinzo points between the OMI and AP groups. High incidence of positive REPP test results at the lung and heart III (shinyu) points occurred only in the AMI group, and this was significantly high when compared with the control group. PMID- 8504577 TI - A simultaneous study of Doppler-echo and catheterization in noninvasive assessment of the left ventricular dp/dt. AB - To confirm the feasibility and accuracy of the method for the noninvasive measurement of the left ventricular dp/dt, 53 patients with mitral regurgitation underwent simultaneous determination of left ventricular dp/dt by continuous-wave Doppler echocardiography and cardiac catheterization. Doppler-determined left ventricular dp/dt is derived from the Doppler mitral regurgitant spectrum by dividing the magnitude of the left ventricular-atrial pressure gradient rise between 1 and 3 m/s of the mitral regurgitant velocity signal by the time taken for this change. Left ventricular dp/dt by Doppler ranged from 629 to 3494 mmHg/s (mean +/- SD, 1971 +/- 785 mmHg/s), and that by catheterization varied between 716 and 3650 mmHg/s (mean +/- SD, 1974 +/- 727 mmHg/s). There was a high correlation (r = 0.93, y = 0.862x + 274.77, SEE = 271 mmHg/s, p < 0.001) of left ventricular dp/dt between the two techniques. It is concluded that left ventricular dp/dt is one of the most commonly used parameters for the evaluation of left ventricular systolic function and that Doppler echocardiography provides a new, accurate and noninvasive method of evaluation. PMID- 8504578 TI - The effect of magnesium versus verapamil on supraventricular arrhythmias. AB - Magnesium has previously been used in the treatment of various arrhythmias, but few randomized and prospective studies are available. In a single-blind study, the efficacy and safety of intravenous magnesium sulfate (bolus doses of 5 + 5 mmol followed by infusion of 0.04 mmol/min) versus verapamil (5 + 5 mg followed by 0.1 mg/min) was evaluated in 57 patients with supraventricular arrhythmias (supraventricular tachycardia, atrial fibrillation, and atrial flutter) of recent onset (less than 1 week). Fifteen (58%) of the patients receiving magnesium (n = 26) converted to sinus rhythm within 4 h, and 16 (62%) within 24 h. Verapamil caused a lower ventricular rate, but only six (19%) of the patients (n = 31) converted to sinus rhythm within 4 h (p < 0.01) and 16 (52%) within 24 h (NS). No side effects were observed during magnesium infusion, whereas six patients receiving verapamil had to be withdrawn from further study medication due to symptomatic side effects (hypotension in three, cardiac failure in three). Magnesium appears to be an effective and safe drug for the treatment of supraventricular arrhythmias. The overall efficacy for conversion to sinus rhythm is at least as effective as with verapamil, and its action is more rapid. PMID- 8504579 TI - Anatomy, histology, and pathology of the cardiac conduction system--Part III. AB - The cardiac conduction system may be affected by various pathologic changes. Some of these changes are general and affect the nonconduction system tissues of the heart (atrophy, fibrosis, necrosis, segment deposition, mineral) and others are more localized to the conduction system (Lev and Lenegre disease). Pathologic conditions associated with atrial, junctional, and ventricular arrhythmias are reviewed. PMID- 8504580 TI - Ethanol-induced myocardial ischemia: close relation between blood acetaldehyde level and myocardial ischemia. AB - A patient with vasospastic angina who developed myocardial ischemia following ethanol ingestion but not after exercise was described. Myocardial ischemia was evidenced by electrocardiograms (ECGs) and thallium-201 scintigrams. The blood acetaldehyde level after ethanol ingestion was abnormally high. The time course and severity of myocardial ischemia coincided with those of the blood ethanol and acetaldehyde level. Coronary arteriography showed ergonovine maleate-induced coronary vasospasm at the left anterior descending coronary artery. ECG changes similar to those induced by ethanol ingestion were observed at the same time. These findings suggest that the high blood acetaldehyde level might be responsible for the development of coronary vasospasm and myocardial ischemia in this patient. PMID- 8504581 TI - Systolic apical filling in a patient with progressive apical hypertrophic cardiomyopathy and giant negative T waves. AB - A relatively asymptomatic 58-year-old non-hypertensive male developed changes of remarkable apical hypertrophic cardiomyopathy associated with deep negative T wave change and marked ventricular dyssynergy without apparent precipitating cause over a nine-year period. PMID- 8504582 TI - Stent wire cutting during coronary directional atherectomy. AB - Directional atherectomy represents one potential approach for the treatment of restenosis in stented coronary arteries. In this case report we demonstrate an important pitfall of this angioplasty technique for stent restenosis--inadvertent entanglement of the stent wire in the device. While cutting and removal of part of the wire was achieved in the case presented, this potential adverse event limits the applicability of directional atherectomy for restenosis in coronary stents. PMID- 8504583 TI - Sir John McMichael, 1904-1993. PMID- 8504584 TI - Structural basis for pathologic left ventricular hypertrophy. AB - Left ventricular hypertrophy (LVH) is a major risk factor associated with the emergence of symptomatic congestive heart failure. Cardiac myocyte excitation contraction coupling has been the biochemical focus in the search for insights into the impaired contractility, relaxation, and stiffness of the hypertrophied myocardium. Although hypertrophied myocytes are the hallmark of LVH, other aspects of myocardial structure may be altered to impair pump function- specifically an abnormal accumulation of connective tissue (interstitial fibrosis). Cardiac fibroblasts, which are nonmyocyte cells of the cardiac interstitium, synthesize and degrade collagen and, therefore, represent an important determinant of pathologic LVH. Significantly, this reactive fibrosis has been found not only in the pressure-overloaded hypertrophied left ventricle but also in the normotensive, nonhypertrophied right ventricle of animals with experimental hypertension. These findings suggest the involvement of a circulating substance that has access to the coronary circulation common to both ventricles. Based on in vivo studies that examined this hypothesis, it can be concluded that chronic elevation of circulating aldosterone, relative to sodium intake, is associated with myocardial fibrosis, which initially adversely alters diastolic function and ultimately systolic ventricular function. The mechanisms by which fibroblast collagen metabolism is invoked in this setting are under investigation. Elucidation of these mechanisms may prepare the way to the prevention as well as the reversal of myocardial fibrosis and, in turn, of pathologic LVH. PMID- 8504585 TI - Left ventricular hypertrophy: should it be reduced? AB - Left ventricular hypertrophy (LVH) is a structural adaptation of the heart to sustained hypertension, serving to normalize increased wall stress. Recent clinical studies have indicated that LVH is a powerful pressure-independent risk factor for cardiovascular morbidity and mortality, particularly sudden death, acute myocardial infarction, and congestive failure. The pathophysiologic sequelae of LVH consist of reduced ventricular filling and contractility, ventricular dysrhythmias, and diminished coronary reserve or myocardial ischemia. LVH can be reduced by antihypertensive therapy, although not all drugs are equipotent in this regard. Angiotensin-converting enzyme (ACE) inhibition seems to be the most powerful monotherapeutic modality for reducing LVH. Recent studies have shown that such a reduction also improves the pathophysiologic sequelae of LVH and maintains left ventricular pump function. Although the reversal of these pathophysiologic events is encouraging, it remains unknown whether reducing LVH will ultimately decrease the excessive risk of sudden death, acute myocardial infarction, and congestive heart failure that has been associated with this disorder independently of arterial pressure. PMID- 8504586 TI - Post-MI remodeling. AB - Two myocardial processes are initiated by acute myocardial infarction: hypertrophy of residual myocardium and a change in left ventricular chamber dimension. The sequence of these events appears to be critically dependent on the size of the infarct and its distensibility, on the load placed on the myocardium, on the metabolic state of adjacent and remote myocardium, and on the degree of activation of tissue hormone systems. Hypertrophy may occur transversely (concentric) or longitudinally (eccentric). The chamber may enlarge because of cell lengthening or slippage or because of infarct expansion. An increase in radius of curvature intensifies wall stress and metabolic demands, whereas increased wall thickness moderates stress. In a canine experimental model of acute regional myocardial necrosis, hypertrophy and dilatation appear to have a different time course, and both may be attenuated by pharmacologic intervention with either an angiotensin-converting enzyme (ACE) inhibitor or a nitrate. The relative contributions of load reduction, hormone inhibition, and the metabolic effect of pharmacologic intervention need further study. Targeting therapy to the prevention of detrimental ventricular remodeling may be a rational approach but one that needs clinical confirmation. PMID- 8504587 TI - Clinical experience in protecting the failing heart. AB - Several large, carefully randomized studies of pharmaceutical agents in the treatment of patients with congestive heart failure (CHF) and left ventricular dysfunction have demonstrated conclusively that angiotensin-converting enzyme (ACE) inhibitors reduce mortality among patients with CHF, as well as the number of hospitalizations for heart failure, myocardial infarction (MI), and angina. ACE inhibitors also have been shown to prevent the development of heart failure in patients with asymptomatic left ventricular dysfunction. Phosphodiesterase inhibitors and the beta agonists have been shown to increase mortality with no beneficial effect on morbidity. The role of digitalis remains controversial. On the one hand, the limited data available suggest that digoxin prevents clinical deterioration in patients with heart failure, even in the presence of sinus rhythm. On the other hand, when administered after MI, digoxin has been associated with increased mortality. Such conclusions are unreliable, however, since it is impossible to adjust statistically for the fact that digoxin is used in sicker patients. This question will be addressed in a large randomized study currently being conducted by the Digitalis Investigation Group. Pharmacologic approaches to the reduction of sudden death currently being explored include amiodarone, oral magnesium supplements, and beta blockers. According to the Cardiac Arrhythmia Suppression Trial and other studies, the class I antiarrhythmic agents appear unpromising or even harmful. The calcium channel blockers also appear to be contraindicated as routine therapy for CHF. PMID- 8504588 TI - Local contractile and growth modulators in the myocardium. AB - Symptomatic congestive heart failure is the culmination of a process that evolves over many years. The long preclinical, or "incubation," period is the setting for a broad range of so-called local activities, including those involved in myocardial remodeling. Growth factors, cytokines, and vasoactive substances are central to this dynamic process, as are different populations of myocardial and circulating cells. The effects of angiotensin, endothelin, endothelium-derived relaxing factor, transforming growth factor-beta, and platelet-derived growth factor on myocardial structure, contractile function, and blood flow are outlined. The mechanisms involved in the activation of interleukin-1 and of tumor necrosis factor are examined within the context of the pathologic process. PMID- 8504589 TI - Anterior dislocation of the shoulder and rotator cuff rupture. AB - Thirty-seven patients older than 40 years of age were seen after sustaining primary anterior dislocations of the shoulder. An associated rupture of the rotator cuff in each patient had been missed, often being mistaken for an axillary neuropathy. Eleven of these patients developed recurrent anterior instability that was due to rupture of the subscapularis and anterior capsule from the lesser tuberosity. In no patient was there a Bankart lesion. Repair of the capsule and subscapularis restored stability in all of the patients with recurrence. PMID- 8504590 TI - The diagnosis and treatment of anterior instability in the throwing athlete. AB - In the overhand or throwing athlete, the shoulder is extremely vulnerable to injury due to the repetitive, high-energy forces. When these stresses are applied at a rate that exceeds that of tissue repair, progressive damage to the shoulder's stabilizing structures can occur. With continued throwing, the static restraints become progressively attenuated, allowing anterior glenohumeral subluxation. Initially, the dynamic stabilizers can compensate for this mild instability with increased muscle activity. Prolonged activity, however, may lead to fatigue. Over time, these compensatory mechanisms can become overloaded. The humeral head then may subluxate anteriorly, where it contacts with the coracoacromial arch, ultimately leading to subacromial impingement. Posterosuperior glenoid impingement may also occur as anterior humeral translation allows the undersurface of the tendinous portions of the supraspinatus and infraspinatus to impinge along the posterosuperior border of the glenoid rim. Fortunately, conservative management is effective in most chronic overuse injuries and includes an initial period of relative rest (avoidance of throwing), oral nonsteroidal antiinflammatory medication, a physical therapy program structured to provide local modalities to reduce inflammation, and a strengthening program for the rotator cuff and scapular rotators. For those athletes with continued symptoms, surgical intervention may become necessary. The appropriate surgical treatment depends on the diagnosis. In the young throwing athlete with shoulder pain, it is essential to recognize that instability or occult subluxation, rather than impingement, is the primary underlying pathology. The anterior capsulolabral reconstruction addresses the problem of instability by correcting the capsular redundancy or labral damage or both. When performed in the manner described, muscle attachments and proprioceptive muscle fibers are not disturbed and full shoulder range of motion can quickly be achieved. This most recent surgical technique and postoperative rehabilitation program has resulted in a significant improvement in the ability to correct instability in those athletes who have failed a prolonged course of conservative care. Prevention of these injuries may be attained, it is hoped, through continued research into the basic biomechanics and the pathoanatomy associated with overhand sports.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504591 TI - The treatment of posterior subluxation in athletes. AB - Posterior instability in athletes is a diagnostic and therapeutic challenge. Athletes have recurrent posterior subluxations rather than true dislocations, and they have pain rather than instability, which makes the diagnosis difficult. The pathology is usually capsular laxity rather than a true reverse Bankart lesion. There is not one diagnostic test, including computed tomography (CT) arthrogram, magnetic resonance imaging (MRI), or arthroscopy, that will always help with the diagnosis. Most athletes respond to conservative care with an exercise program designed to strengthen the posterior deltoid, the infraspinatus, and the teres minor; but, there is still a select group of athletes that cannot perform their sport after an extensive rehabilitation program. The surgical options for these athletes are varied, and the results in most cases are less than ideal. A posterior capsulorrhaphy was performed to treat this problem. This was initially performed with a staple, but this technique has been abandoned for a suture capsulorrhaphy to avoid staple problems. The 40 athletes treated operatively that had adequate follow-up evaluation reflected a 40% failure rate. Most of the failures were related to ligamentous laxity and unrecognized multidirectional instability not treated at the time of surgery. There may be subtle differences between a patient with posterior subluxation and multidirectional instability; these must be differentiated before operation. Also, the higher the competitive level of athlete, the worse the overall results. The high-level athlete must be informed that even if his or her shoulder is stabilized, the functional results may not allow him or her to continue at the same competitive level. PMID- 8504592 TI - Epidural compression of the spinal cord caused by vertebral osteoblastic metastasis of prostate carcinoma. A case report. AB - A 71-year-old man with prostate cancer developed epidural compression of the spinal cord caused by bony protuberances expanding from a vertebral osteoblastic metastasis. Pathologic examination of the metastatic lesion showed that both tumor and thickened vertebral trabeculae broke through the cortex and formed bony protuberances. The periosteal new bone appeared not to arise from a reactive periosteum but from the tumor breaking through the cortex. A biologic interaction between the tumor and the host may be responsible for the rare periosteal new bone formation. PMID- 8504593 TI - Long-term follow-up study of anterior surgery for cervical spondylotic myelopathy with special reference to the magnetic resonance imaging findings in 52 cases. AB - A series of 151 patients with cervical spondylotic myelopathy (CSM) were surgically treated through an anterior approach in the period from 1960 to 1987. Particular attention was given to the results of the 52 patients who were operated on more than 12 years ago. Satisfactory short-term results were obtained in all but the few who had incomplete decompression. In these patients, function deteriorated within five years. A disturbing incidence of progression of myelopathy was noted ten years after surgery. Magnetic resonance imaging identified many of the causes (e.g., newly developed intervertebral disk herniation and progression of spondylosis associated with spinal malalignment in both cephalad and caudal directions). Other adverse changes were hypertrophy of the yellow ligament and ossification of the posterior longitudinal ligament. The new and improved techniques consist of decompression to a width of 16 mm or more with intraoperative ultrasonography in addition to extirpation of the posterior longitudinal ligament. This new measure may reduce the incidence of late neurologic deterioration. PMID- 8504594 TI - A prospective randomized comparison of two surgical approaches to total hip arthroplasty. AB - One hundred patients had total hip arthroplasty (THA) with either a modified Hardinge approach or transtrochanteric lateral approach. Perioperative data showed that osteotomies resulted in significantly more blood loss but required shorter operative time. Postoperative pain, using a visual analog scale, showed no statistical difference between the two groups. Postoperative hip scores for pain, function, and range of motion (ROM), presence of limp, and abductor muscle strength scores showed no significant difference between groups at six months and one year. Roentgenographic follow-up evaluation showed a mean acetabular cup angle of 40 degrees and a neutral-to-valgus femoral stem position in all patients. Trochanteric union was present in 92%. Heterotopic ossification occurred predominantly in the Hardinge patients but was not functionally significant. Therefore, the ability to achieve adequate pain relief and function with THA is not affected by the type of approach. PMID- 8504595 TI - Femoral windows in revision total hip arthroplasty. AB - In 21 revision total hip arthroplasties (THA), a 2-5-cm window was cut into the anterolateral cortex of the femur, and the cement distal to the window was removed under direct vision. In each case, a cemented THA was revised to a noncemented implant that bypassed the window by at least two femur diameters. The section of cortical bone was replaced; autogeneic bone graft was applied to the osteotomy site, and cerclage wires were used to hold the window in place. Postoperatively, all patients were maintained at partial weight-bearing (touchdown) for six weeks and then advanced as they were able. The mean follow-up time in this series was 22 months. Access to the femoral cement was greatly facilitated by the use of a femoral window. There were no intraoperative femoral fractures or inadvertent femoral perforations during cement removal. The mean healing time for the windows was 17 weeks. There was no association of femoral thigh pain or implant loosening with femoral windows. The windows heal rapidly and have not been associated with perioperative femoral fractures. PMID- 8504596 TI - The viability of the femoral head after resurfacing hip arthroplasty in humans. AB - Histologic examination of 72 femoral heads retrieved at revision of resurfacing arthroplasties was performed to determine the possible role of generalized osteonecrosis caused by avascular necrosis (AVN) in early loosening of the femoral components. The degree of loosening at the femoral bone-cement interface was correlated with the histologic appearance of the femoral heads. None of the ten femoral heads with solid femoral components and only one of the 15 heads with slight loosening showed evidence of generalized osteonecrosis. The one case might have been attributable to AVN after the resurfacing procedure. In the remaining femoral heads with marked loosening of the femoral component, necrosis of bone was uncommon. When present, it was attributed to loosening. Thickening of bone trabeculae, a fibrovascular marrow, and superficial necrosis of bone of the femoral head are not evidence of generalized AVN caused by the resurfacing arthroplasty procedure, but are the result of remodeling changes and subsequent loosening. PMID- 8504597 TI - Ten-year follow-up study of missed, simultaneous, bilateral femoral-neck fractures treated by bipolar arthroplasties in a patient with chronic renal failure. AB - Fracture of the femoral neck associated with seizure disorders is uncommon. Bilateral fractures of the femoral neck are exceedingly rare. Early recognition of the fracture is essential. A patient with unrecognized bilateral femoral-neck fractures with nonunion was successfully treated by bilateral, bipolar hip arthroplasty. PMID- 8504598 TI - Traumatic posterior acetabular defects reconstructed with iliac crest autograft. A report of two cases. AB - In two cases of posterior wall acetabular fracture, the fracture fragment was too comminuted to be fixed per primam. A full-thickness iliac crest autograft was used as initial reconstruction in these two cases. Although the reconstruction was not anatomic, one of the two patients is functioning with only minimum symptoms at five years. Incorporation of the autograft has been documented in both cases. Although the procedure may not accurately reproduce the anatomy of the hip joint, it will appropriately supplement viable acetabular bone structure. PMID- 8504599 TI - Psoas tenotomy and heterotopic ossification after Charnley low-friction arthroplasty. AB - One hundred twelve cases of Charnley low-friction arthroplasty (LFA), with elevation of the psoas tendon from the lesser trochanter, were reviewed. Twenty six (23.3%) had heterotopic ossification in that area. No heterotopic ossification was present in 124 cases without psoas tenotomy. Periosteal elevation at the time of tenotomy is a likely cause of psoas heterotopic ossification. PMID- 8504600 TI - Tibial fracture stability. Analysis of external fracture immobilization in anatomic specimens in casts and braces. AB - Plaster casts, custom-fabricated fracture braces, and prefabricated fracture braces were compared in the laboratory for the stability they provided to closed, experimental, diaphyseal fractures of the tibia and fibula on anatomic specimens. The stability was comparable for each type of device tested for the loading conditions of isolated compression, bending, and torsion. Length stability (overriding at the fracture site) was poor, rotation was marginal (by clinical standards), and angulation was very good. Selective removal of portions of each cast and brace demonstrated that the classic patellar-tendon-bearing (PTB) extension proximally and below ankle extensions distally had insignificant effects on stability of these middle-third diaphyseal fractures for the conditions tested. The soft-tissue compression provided by a snug, tapered "cylindrical" sleeve, which encompassed the soft tissues from the tibial tubercle to the flare of the distal tibia and fibula, provided the stabilizing effect for all of the devices tested. PMID- 8504601 TI - Mechanisms of glenohumeral joint stability. AB - The biomechanics of glenohumeral stability involve several static and dynamic mechanisms to achieve the intricate balance between shoulder mobility and stability. In conjunction with recent in vitro studies, two important stabilizing mechanisms, concavity compression and scapulohumeral balance, were described. Concavity compression refers to the stability obtained by compressing the humeral head into the concave glenoid fossa. Increasing the magnitude of the compressive load, as provided by dynamic muscle contraction, and the depth of the glenoid concavity, which varies from the asymmetric geometry, enhance concavity compression stabilization. The related scapulohumeral balance refers to the dynamic positioning of the glenohumeral joint so that the joint reaction force is balanced within the glenoid fossa. The greater the arc provided by the glenoid, the larger the range of joint force angles acting through the humeral head that may be stabilized. The presence of an intact glenoid labrum is important to both mechanisms. Concavity compression and scapulohumeral balance may be of particular importance to glenohumeral joint stability in the midrange of motion where the capsuloligamentous constraints are lax. Clinical correlation of these mechanisms contributes to the understanding of glenohumeral instability. PMID- 8504602 TI - Fat emboli syndrome in isolated fractures of the tibia and femur. AB - The fat emboli syndrome (FES) was studied in otherwise healthy young skiers with isolated fractures of the tibia and femur treated from 1980 until 1991. During the first year, 13 of 56 tibial and femoral fractures developed FES. The overall incidence of FES was 23%: 19% among fractured tibiae and 75% among fractured femora. Thirty-three percent of displaced transverse tibial fractures developed FES. During the next ten year, only those tibial or femoral fractures that developed FES were studied. There were 44 such cases. Symptoms included a mean PO2 of 45 mm Hg and a fever of 39 degrees. In addition, 40% of the patients had petechiae. The mean patient age was 26 years. None of the patients had other significant injuries or illnesses, 75% received oxygen, and 9% received steroids. None of the patients received mechanical ventilation. All cases had developed by the third day of hospitalization, and the duration of the syndrome was less than four days in 86% of the patients. The mortality rate was 0%. In 50% of the patients, hospitalization was prolonged because of FES; otherwise, there were no complications. This study of isolated femoral and tibial fractures in healthy young skiers demonstrates that FES occurs more commonly than previously thought, is not associated with mortality, and causes little morbidity. Treatment should consist of supportive care only, with specific care directed toward the underlying injury. PMID- 8504603 TI - Giant cell tumor of the sacrum. AB - Twenty-six patients (18 women and eight men) with giant cell tumors of the sacrum were treated from 1960 through 1986. The mean age of the patients was 29 years. The follow-up duration averaged 7.8 years. A neurologic deficit was present in 88%. Sixteen patients had not had a previous operation. Ten patients were referred for local recurrence. Twenty-one patients had radiation therapy; malignant transformation later occurred in three. Three benign giant cell tumors metastasized to the lungs. The local recurrence rate for patients treated by curettage was 33%. Three patients died of tumor-related complications. At the completion of this study, two patients were alive with disease. The suggested initial treatment is complete curettage. Radiation therapy should be reserved for incomplete resection and local recurrence. Occasionally, patients may require wide resection, which may cause a severe neurologic deficit and compromise spinal stability. PMID- 8504604 TI - Soft-tissue myxomas and fibrous dysplasia of bone. A case report and review of the literature. AB - An association between fibrous dysplasia and myxomas (soft-tissue neoplasms of mesenchymal origin) has been described in the literature. The authors report another such case of fibrous dysplasia/myxoma coexistence: a patient with polyostotic fibrous dysplasia who developed right anterior thigh pain from a solitary intramuscular myxoma. After a thorough review of the literature, the authors found that a causal relationship between fibrous dysplasia and myxomata remains uncertain. To ensure an adequate and accurate diagnosis, however, patients with soft-tissue myxomas should be thoroughly evaluated for fibrous dysplasia. A proper investigation of soft-tissue masses also should be carried out to exclude malignancy. PMID- 8504605 TI - Osteoid osteoma diagnosis and management with low morbidity. AB - Wide excision, a recommended treatment for osteoid osteoma, creates needless resection of surrounding bone and causes difficult intraoperative nidus identification. Less bone resection is required by successively burring through the reactive bone to identify the nidus, which is then removed with curettes and burrs. This burr-down technique requires precise preoperative anatomic localization by thin section (1-1.5 mm) computed tomography (CT) scans. In a consecutive series of 19 osteoid osteomas, 18 were accurately diagnosed before operation, using a combination of clinical findings, plain roentgenograms, and CT scans. The burr-down technique was successfully used in 15 cases, and four were treated with wide excision. There have been no local recurrences. The follow-up period for all 19 patients was at least six months. No bone grafts were required in the burr-down group in nonspinal locations; there have been no fractures despite early return to unrestricted activity. The burr-down technique was associated with less postoperative immobilization, a shorter duration of protected weight bearing, and an earlier return to activity. The burr-down technique is recommended for accessible osteoid osteoma lesions. PMID- 8504606 TI - Lengthening of congenital lower limb deficiencies. AB - Eighty-three lengthening procedures were performed in 71 patients with congenital shortening of the lower limb. Mean lengthening achieved was 7 cm, which represented a mean increase of 24% of the initial bone length. Seventy-nine percent of patients had at least one preexisting joint deformity or instability. The devices used and the bone lengthened for the 83 procedures were divided into three groups. Fifty-one femurs (Group I) and 18 tibiae (Group II) were lengthened using the Wagner device, and 14 tibiae (Group III) were lengthened using the Ilizarov device. The final goal of lengthening was rated as good, fair, or poor. Good results were obtained in 55% of the procedures, fair results in 33%, and poor results in 12%. Poor results were most frequent in Group I (18%), whereas no poor result was reported in Group III. Complications occurred in 77% of patients. No significant difference could be demonstrated in the complication incidence of Groups II and III. Complications were significantly more frequent and results generally poorer when the lengthening exceeded 25% of the initial bone length or when the femur was lengthened. PMID- 8504607 TI - Congenital pseudoarthrosis of the radius. A case report and review of the literature. AB - Congenital pseudoarthrosis of the radius (CPR) is rare. Only ten cases seem to have been found in the literature. Congenital pseudoarthrosis of the radius usually is associated with neurofibromatosis or fibrous dysplasia. This is a report of a congenital pseudoarthrosis of the left radius associated with congenital dislocation of the left hip in a five-month-old girl. Apart from the pseudoarthrosis, there were no visible abnormalities. This patient was treated successfully with excision of the pseudoarthrosis, shortening osteotomy of the ulna, grafting, and intramedullary fixation of both the radius and the ulna. Review of the literature disclosed the extreme difficulties in treating this condition. It was also found that vascularized fibular graft has been used successfully. PMID- 8504608 TI - Autotransfusion in the postoperative orthopedic patient. AB - Transfusion of autologous blood has become increasingly important as an alternative to the use of conventional allogeneic products. Some areas of autotransfusion, like predeposit and intraoperative salvage, are well standardized and generally recommended by physicians. In many orthopedic surgical procedures, the postoperative drainage constitutes a significant percentage of the total perioperative blood loss. Recently, reinfusion of this salvaged, unprocessed autologous blood has been widely advocated; however, reports on its quality are infrequent in the literature. This pilot study, based on sophisticated laboratory testing, describes an efficient method whereby postoperatively shed blood can be appropriately processed and returned to the patient as a relatively safe product. PMID- 8504609 TI - Radiologic features of shoulder instability. AB - Roentgenographic studies in a patient with shoulder instability generally identify the presence of a Hill-Sachs lesion, the presence of bony abnormalities of either the anterior or posterior rim, the presence or absence of fractures, and thick pathologic changes in the joint structure, which not only may provide insight into the diagnosis, but also may give the clinician insight into whether these pathologic changes are likely to be improved with operative and nonoperative treatment modalities. Clearly, the anteroposterior view, particularly with internal rotation, seems important in the diagnosis of the unstable shoulder. The West Point axillary view seems to be a useful one to identify the presence of glenoid rim problems. An additional view, such as the Stryker notch view, may identify the extent and presence of Hill-Sachs lesion when this may not be present on the other two views. Computed tomography arthrography, magnetic resonance imaging scan, and stress testing probably has limited applicability in the routine roentgenographic diagnosis of the unstable shoulder. PMID- 8504610 TI - Estradiol-induced knee osteoarthrosis in ovariectomized rabbits. AB - Experiments in animals have shown that estrogen is chondrodestructive. The existence of 17 beta-estradiol receptor in rabbit chondrocyte and canine cartilage suggests that estrogen is associated with the development of osteoarthrosis (OA). The increased frequency of knee OA in obese postmenopausal women, who are often associated with hyperestrogenism, suggests a link between estradiol and OA. The pathologic changes induced by nine and 12 weeks of intraarticular injection of high doses of estradiol (0.3 mg/kg body weight/day) and low doses of estradiol (0.06 mg/kg body weight/day) into knee joints of ovariectomized rabbits have been examined. In the high-dose group, loss of condyle surface congruity, thinning, fissuring, and fibrillation of the remaining cartilage surface were observed at Week 9. At Week 12, cartilage erosion extended to the calcified layer, exposing the subchondral bone. Scanning electron microscopy (SEM) further revealed numerous pits, which indicated formation of cysts on the cartilage surface. Injection of low dose estradiol, conversely, did not induce significant pathologic changes. The results demonstrated that the direct interaction of estradiol and rabbit cartilage was dose- and duration dependent. Pathologic changes from the current animal model of knee OA closely resembled those of knee OA in humans. Thus, this model constitutes a potential tool for further studies of the early pathologic changes of OA and the possible prevention of cartilage degeneration by estrogen receptor inhibitors. PMID- 8504611 TI - Recurrent or habitual dislocation of the shoulder-joint. 1923. PMID- 8504612 TI - The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing. AB - Autogeneic cancellous bone graft has been recommended as a vehicle for local antibiotic delivery. Its effect on graft incorporation, however, is unknown. The healing of defects grafted with tobramycin-impregnated cancellous bone were compared with those grafted with cancellous bone alone. Plane roentgenographs, microradiographs, bone density analyses, histologic examination, and biomechanical testing were performed on specimens throughout the course of healing. The presence of large concentrations of local tobramycin does not appear to affect the normal healing characteristics of cancellous bone graft. PMID- 8504613 TI - Diagnosis of shoulder instability by examination under anesthesia. AB - A systematic method of examining the shoulder in anesthetized patients was developed. Humeral translocation on the glenoid was assessed in five directions and in three positions of arm rotation for four of these directions. Fifty-five patients thought to have shoulder instability were evaluated by history taking, physical examination, standard and special roentgenograms, examination under anesthesia, and either shoulder arthroscopy or operation. The findings at examination under anesthesia were compared with the pathologic conditions identified at arthroscopy or operation. Twenty-five shoulders had pathologic evidence of continuing instability: Bankart lesions in 19 and clearly excessive capsular laxity in six. All 25 had abnormal results on examination under anesthesia (no false-negative results). Thirty shoulders had no demonstrable pathologic condition. The results of examination under anesthesia were normal for 28 shoulders and abnormal for two (two false-positive results). The sensitivity of examination under anesthesia in these patients was 100%. The specificity and predictive value were 93%. Examination under anesthesia has proven to be reasonably precise in assessing shoulder stability. If the results of the examination are normal, more complex and invasive diagnostic testing may not be necessary. PMID- 8504614 TI - Arthroscopic manifestations of shoulder subluxation and dislocation. AB - Instruction in the arthroscopy of the normal and pathologic anatomy of various structures of the shoulder associated with instability syndromes is absolutely essential. Arthroscopy is not a substitute for a thorough clinical evaluation and physical examination of the shoulder, however. It provides confirmation of the clinical impression, especially in subtle cases of instability. PMID- 8504615 TI - Arthroscopic shoulder stabilization. A role for biodegradable materials. AB - The use of metallic implants about the shoulder joint can be complicated by loosening, migration, and breakage of the implant. Bioabsorbable implants would be an ideal solution to this problem if their bioabsorption profile could be fine tuned to appropriately share stress with the healing tissues. The development of such an implant must satisfy four basic criteria: (1) The bioabsorbable implant must have adequate initial fixation strength to coapt the soft tissues to bone; (2) The implant's bioabsorption profile must enable it to retain satisfactory strength while the healing tissues are regaining mechanical integrity; (3) The implant must not bioabsorb too slowly or it will behave like its metal counterpart with breakage and migration; and (4) The implant must be made of materials that are completely safe: no toxicity, antigenicity, pyrogenicity, or carcinogenicity. PMID- 8504616 TI - Classification and physical diagnosis of instability of the shoulder. AB - Recent clinical and basic science work has increased our knowledge of shoulder instability. Valuable information has been gained by cutting studies of the capsuloligamentous complex to clarify the biomechanics of instability. It is now clear that a significant overlap exists in the concepts of instability and impingement relating to anterior shoulder pain. These concepts have added new importance to organization and standardization when classifying and diagnosing shoulder instability. This manuscript presents an algorithmic approach to classification of shoulder girdle complaints that may be related to instability. This classification system is designed around the direction, degree, chronology, cause, and volition of instability. With accurate and detailed analysis of the historical presentation, most shoulder instability complaints can be classified using this approach. The physical examination also should proceed in an orderly fashion, including general impression of the musculoskeletal system, inspection, palpation, and range of motion of both the uninvolved and involved shoulder, neurologic examination, rotator cuff evaluation, and stability assessment. Stability assessment includes glenohumeral translation examination with apprehension and provocative testing. Management techniques are predicted on an accurate diagnosis. With a thorough and organized examination, the correct diagnosis can be achieved. PMID- 8504617 TI - Diagnosis and treatment of traumatic anterior instability of the shoulder. AB - Traumatic anterior glenohumeral joint dislocation is the most common type of shoulder instability. Lesions that usually result are avulsion of the anterior capsule and glenoid labrum from the glenoid rim (Bankart lesion), compression fracture of the posterosuperior humeral head (Hill-Sachs lesion), and laxity of the joint capsule. Another common lesion is a lengthwise disruption of the rotator cuff at the interval between the subcapularis and supraspinatus tendons. The shoulder that dislocates repeatedly after trauma has an excellent success rate when treated by surgical repair. The aim of the Bankart procedure is to restore stability to the shoulder by repairing the traumatic lesion of the anterior glenoid rim without altering normal anatomy. PMID- 8504618 TI - Recurrent posterior shoulder instability. Diagnosis and treatment. AB - Recurrent posterior glenohumeral instability is regarded as a difficult problem to diagnose and treat. A careful history and physical examination are the most helpful tools in making this diagnosis. A positive posterior stress test, demonstrable posterior subluxation, and a sulcus sign are frequently present on examination. Special roentgenographic studies, such as the computerized arthrotomography (arthro-CT) scan, may be used in cases in which plain roentgenographs suggest bony glenoid abnormalities. When conservative therapy fails, there is no consensus on the operative treatment. Procedures that address the soft tissues, such as capsulorrhaphy and posterior labral repair, as well as those that alter the bony geometry of the joint, such as posterior bone blocks and glenoid or humeral osteotomies, have been described. Capsular laxity is the most common pathologic finding in the authors' experience, and they favor the use of a posterior-inferior capsular shift procedure to correct this problem. Augmentation of the repair with a posterior bone block is reserved for unusual cases, such as when glenoid hypoplasia is present or in certain revision situations. PMID- 8504619 TI - Congenital anteroinferior instability treated by Bankart repair. AB - A subset of patients with symptomatic anteroinferior instability of the shoulder has been recognized. All patients had a history of minimal trauma that was not related to their symptoms. There were 29 men and four women, averaging 29 years of age. Forty-five percent of the patients had failed treatment for associated impingement syndrome. Eleven patients had 17 operations on the shoulder that failed to relieve pain. Preoperative duration of symptoms ranged from four to 130 months (average, 28 months). No Hill-Sachs lesions were present. After a Bankart stabilization, wherein 11 of 33 shoulders had labral tears, pain relief was achieved in 27 of 33 patients. Three additional patients had pain relief after a second-stage acromioplasty. Thus, three of 15 patients with associated impingement syndrome required a second-stage acromioplasty (20%). In summary, 30 of 33 patients had pain relief. There were three failures. Two of the three patients had multidirectional instability. One of these was lost to follow-up evaluation. Another, repaired by a capsular shift, has no further dislocations. One patient required a revision Bankart repair after he sustained a traumatic tear of the capsule ten days after his initial operation; there was no recurrence. The Bankart operation is a worthwhile procedure for congenital unidirectional anteroinferior instability with or without impingement syndrome. It should be done first rather than initially treating the associated impingement. PMID- 8504620 TI - Testing for drugs of abuse. Pharmacokinetic considerations for cocaine in urine. PMID- 8504621 TI - Drug dosage in patients during continuous renal replacement therapy. Pharmacokinetic and therapeutic considerations. AB - The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised. In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed. These effective detoxification treatments require knowledge of their influence on drug disposition. Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH). Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides. In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin. Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations. With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given. In haemofiltration, drug protein binding is the major factor determining sieving, i.e. the appearance of the drug in the ultrafiltrate. In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate. In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate. Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination. Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value. In case of high nonrenal clearance, the degree of saturation is without clinical significance. Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients. PMID- 8504622 TI - Statistical considerations in pharmacokinetic study design. AB - Pharmacokinetic studies may generally be categorised into 3 types: (a) population based investigations, (b) individual-based compartmental, or (c) individual-based noncompartmental research projects. Each type of study has advantages and limitations. Population-based investigations pool drug concentrations across more than 1 individual subject. From these data, estimates of pharmacokinetic parameters are calculated. NONMEM is the only computer program available to evaluate this type of information. Recently a method has been proposed which derives individual estimates from the information available from NONMEM. By combining these 2 procedures it is possible for the clinician to review and adjust the dosage regimen if necessary. Population-based studies require fewer design criteria than other methods and are adaptable to the clinical setting, i.e. subjects can be patients currently being treated with the drug under consideration. One distinct advantage to this type of study is the flexibility of sampling times and the capability of the clinician to use information from the critically ill, the geriatric patient or the very young child. These subjects would not be available for the individual-based type of study because of the relatively large number of samples needed. Individual-based pharmacokinetic studies can be divided into 2 types with respect to their evaluation: (a) compartmental and (b) noncompartmental investigations. The latter type of study was originally thought to require fewer assumptions than the former but subsequently it has been shown that noncompartmental analyses are more restrictive and are basically compartmental in their approach. These studies estimate parameters which the compartmental investigation does not usually consider. These include area under the moment curve (AUMC) and mean residence time (MRT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504624 TI - Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine. AB - The plasma concentrations and renal clearance values of morphine, morphine-3 glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined in 11 adult cancer patients maintained on a long term oral morphine dosage (10 to 100mg every 4h). Concentrations in plasma and urine were determined by a specific high performance liquid chromatography assay. In this group of patients, whose creatinine clearance values ranged from 52 to 180 ml/min (3.12 to 10.8 L/h), average steady-state plasma concentrations of morphine, M3G and M6G were related (p < 0.01) to the morphine dose per kilogram of bodyweight. The mean total urinary recovery as morphine, M3G and M6G was 74.6 +/- 26.5% of the dose. Renal clearance values for M3G and M6G were closely related (r2 = 0.80; p < 0.0005). It was not possible to detect a relationship between the renal clearance of morphine, M3G and M6G, and that of creatinine. The renal tubular handling of all 3 compounds showed wide interindividual variation, and there was evidence of either net renal tubular secretion or reabsorption. There was no apparent relationship between plasma morphine and M6G concentrations and pain relief. PMID- 8504623 TI - Pharmacokinetic optimisation in the treatment of Pneumocystis carinii pneumonia. AB - Several drugs and drug combinations are currently used in the treatment of patients with Pneumocystis carinii pneumonia (PCP)--pentamidine and cotrimoxazole (trimethoprim plus sulphamethoxazole), which are indicated for this usage, dapsone/trimethoprim and clindamycin/primaquine, which are not licensed for PCP, and trimetrexate/calcium folinate (leucovorin), eflornithine and BW-566C (566 C80) as investigational drugs. For most of these agents, recommendations regarding the use of pharmacokinetic parameters to establish individualised therapy cannot be made. The pharmacokinetics of antipneumocystis drugs are not well documented and clinical trials evaluating the relationship between the individual plasma pharmacokinetic profiles and responses to treatment are sparse. In clinical trials, the reduction of the daily dose of pentamidine to 3 or 2 mg/kg/day and of cotrimoxazole to 15 mg/kg of the trimethoprim component resulted in a substantial reduction of frequency and severity of adverse drug effects without diminishing efficacy. For pentamidine, a long half-life of > or = 4 days implies the need for a loading dose. Plasma concentrations of the parent drug at steady-state varied between 30 and 100 micrograms/L. The elimination pharmacokinetics are characterised by several elimination slopes indicating the existence of a deep peripheral compartment. Due to its very low renal clearance, dosage adjustments are not necessary in patients with renal impairment. The pharmacokinetics of cotrimoxazole follow first-order kinetics in PCP and the particular parameters are similar to those reported in the treatment of bacterial infection. Steady-state plasma concentrations of both trimethoprim and sulphamethoxazole are attained within 2 to 3 days, but the range of 'therapeutic' plasma concentrations must be newly defined, since elevated trimethoprim concentrations could not be correlated with the frequency and severity of adverse drug reactions. The concentrations of sulphamethoxazole may be at least as important as those of trimethoprim in defining a toxic range. With dapsone/trimethoprim, clindamycin/primaquine and BW-566C (566 C 80) good clinical response rates were found in groups of patients with mild to moderate PCP. Comparative trials with standard drugs are still ongoing. Therapeutic to toxic concentration ratios have not been established in patients with PCP. Pharmacokinetic data pertaining to patients with PCP are either nonexistent or incomplete, or are complicated by a drug interaction between dapsone and trimethoprim suggesting an inhibition of metabolism of dapsone. Eflornithine and trimetrexate/calcium folinate have been used under specific research protocols, showing partial success as salvage agents for desperately ill patients with AIDS. Regarding all antipneumocystis drugs, additional clinical and pharmacokinetic data are needed to optimise and more fully individualise the treatment regimens for this severe infection. PMID- 8504625 TI - Pharmacokinetics of temocapril and enalapril in patients with various degrees of renal insufficiency. AB - Temocapril is a novel ACE inhibitor that is cleared via dual excretion routes in humans. Borderline or mildly hypertensive patients with normal renal function [group 1, creatinine clearance (CLCR) > 70 ml/min (4.2 L/h), n = 12], moderate renal impairment [group 2, CLCR 30 to 70 ml/min (1.8 to 4.2 L/h), n = 12] or severe renal impairment [group 3, CLCR < 30 ml/min (1.8 L/h), n = 12] received a single oral dose of either temocapril 1 mg (n = 6, each group) or enalapril 5mg (n = 6, each group). These 2 drugs gave similar values for the area under the plasma concentration-time curve (AUC) of the active diacids. The maximum plasma concentration of enalapril diacid was increased 2- and 6-fold in moderate and severe renal impairment, respectively, whereas that of temocapril diacid was not altered. The AUC of enalapril diacid increased 13-fold at CLCR values < 30 ml/min, but that of temocapril diacid increased only 2-fold. The duration of plasma ACE inhibition due to enalapril was greatly prolonged by the impairment of renal function, whereas that due to temocapril was affected very little. Urinary recovery of temocapril diacid was decreased markedly in patients with severe renal dysfunction, most probably because the diacid was excreted through the biliary route. On the other hand, urinary recovery of enalapril diacid remained fairly high even in patients with severe renal impairment, because of extremely high plasma diacid concentrations resulting from the lack of biliary excretion. These observations suggest that temocapril is beneficial in the treatment of hypertension in patients with severely impaired renal function. PMID- 8504627 TI - The endothelin family of peptides: local hormones with diverse roles in health and disease? PMID- 8504626 TI - Pharmacokinetics of indomethacin in the elderly. AB - In a cross-sectional study the pharmacokinetics of indomethacin were studied in old and young adults without manifest organ failure. Total clearance of indomethacin after a single oral dose of 50mg was 0.8 ml/min/kg in elderly individuals (mean 79.5 +/- 1.3 years) compared with 1.4 ml/min/kg in younger individuals (mean 36.9 +/- 3.0 years). The apparent elimination rate constant averaged 0.23 h-1 in the aged and 0.32 h-1 in the young people. Oral bioavailability was close to 1 in the young but 0.77 in the elderly. The apparent volume of distribution was similar in each group. Based on these results it is suggested that the maintenance dose of indomethacin be reduced by 25% in the elderly. PMID- 8504628 TI - Rapid and selective inhibition of platelet aggregation and thromboxane formation by intravenous low dose aspirin in man. AB - 1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3-5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation. 4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by > 85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (-83.2%) and low dose (-67.4%)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504629 TI - Dissociation between pressor sensitivity in vivo and contractile reactivity in vitro to angiotensin II in rats with experimental cirrhosis. AB - 1. Decreased pressor sensitivity to angiotensin II occurs in cirrhosis, but the mechanism remains unclear. 2. Angiotensin II dose-response studies were performed in conscious, chronically instrumented cirrhotic and control rats, and angiotensin II concentration-response studies were performed in isolated blood vessels obtained from similar groups of animals. 3. Cirrhotic rats demonstrated a significantly decreased pressor response to angiotensin II (5-80 ng/kg intravenously). However, angiotensin II-generated tension in thoracic aortic rings isolated from cirrhotic rats and studied in vitro was not impaired. These findings are consistent with the concept that circulating vasodilator substances in cirrhosis rather than an abnormality intrinsic to vascular smooth muscle cells are responsible for the decreased pressor sensitivity to angiotensin II in vivo. 4. Pretreatment with the cyclo-oxygenase inhibitor indomethacin (3 mg/kg intravenously) restored pressor sensitivity to angiotensin II to normal, suggesting that cyclo-oxygenase products, possibly vasodilator prostaglandins, may be involved in mediating pressor resistance to this hormone in vivo. PMID- 8504630 TI - Effect of insulin-dependent diabetes mellitus on lipids and lipoproteins: a study of identical twins. AB - 1. Forty-five identical twin pairs, discordant for insulin-dependent diabetes mellitus, were studied with respect to their serum lipid (high-density lipoprotein, low-density lipoprotein, total cholesterol and triacyl-glycerol) and apoprotein [apoprotein A-I, apoprotein B and lipoprotein (a)] concentrations and apoprotein (a) phenotypes. The twins were compared with an age- and sex-matched non-diabetic control group. 2. A significantly higher value was found only for high-density lipoprotein cholesterol in the diabetic twins of the female twin pairs. 3. Highly significant correlations existed between the twin pairs for all lipids and lipoproteins measured, particularly lipoprotein (a), for which identical apoprotein (a) isoforms were also found. 4. Correlations existed between the non-diabetic twins and the control subjects for high-density lipoprotein cholesterol and apoprotein A-I, probably due to the rigorous matching of control subjects. 5. The similarity between values for lipids and lipoproteins in the non-diabetic twins and control subjects suggested no effect of a genetic susceptibility to insulin-dependent diabetes mellitus. The differences in lipoproteins we describe for the identical twins discordant for insulin-dependent diabetes mellitus, in whom there was no evidence of a raised urinary albumin excretion rate, does not appear to explain the excess mortality from cardiovascular disease reported in patients with this disease. PMID- 8504631 TI - Utilization of non-protein nitrogen in whey-dominant formulae by low-birthweight infants. AB - 1. The effects of increasing non-protein nitrogen intake on nitrogen balance and alpha-amino nitrogen flux rate using [15N]glycine were examined in 30 low birthweight appropriate-for-gestational-age infants (birthweight 1.5-2.0 kg). The compositions of the three whey-dominant formulae were similar except for the ratios of non-protein nitrogen/protein nitrogen, which were 6.5:93.5, 11.4:88.6 and 17.5:82.5. 2. Infants in the three diet groups each received similar total nitrogen intakes (395 mg of N day-1 kg-1, SD 2.6; n = 3). Protein nitrogen and non-protein nitrogen intakes were different as expected. Energy absorption (449 kJ day-1 kg-1, SD 13; n = 3) did not differ significantly between groups. A similar weight gain was observed in all groups. 3. Nitrogen absorption (76%, SD 4; n = 3) was not significantly different between groups. Apparent urea balance was significantly increased and became positive in the group receiving the formula with the higher proportion of non-protein nitrogen and urea nitrogen. Nitrogen retention, however, was significantly depressed in this group, indicating decreased efficiency of nitrogen utilization at this level of non protein nitrogen despite an enhanced urea salvage. 4. The enrichment of the 15N label in urinary urea at isotopic steady state was significantly reduced in infants receiving the highest urea-containing formula, presumably due to the dilution of 15N-labelled urea by dietary urea. No difference, however, was found in the enrichment of the 15N label in urinary ammonia. Rates of alpha-amino nitrogen flux, protein synthesis and protein breakdown calculated from the ammonia labelling did not differ significantly between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504632 TI - Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans. AB - 1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504633 TI - What is the blood flow to resting human muscle? AB - 1. An investigation was carried out in five healthy lean adults to assess whether forearm and calf plethysmography largely reflect muscle blood flow as measured by 133Xe and whether there is substantial variability in the blood flow to muscles located at different sites in the body. 2. Blood flow to forearm and calf flexors and extensors, biceps, triceps and quadriceps was assessed using the 133Xe clearance technique. Blood flow to forearm skin and subcutaneous adipose tissue was also measured using the 133Xe clearance technique, whereas blood flow to the forearm and calf was measured using strain gauge plethysmography. 3. The mean blood flow to different muscles ranged from 1.4 +/- 0.6 (gastrocnemius) to 1.8 +/ 0.7 (forearm extensor) ml min-1 100 g-1 muscle (1.4 +/- 0.6 and 1.9 +/- 0.8 ml min-1 100 ml-1 muscle, respectively) but there were no significant differences between them. Forearm and calf blood flows (2.7 +/- 0.3 and 3.0 +/- 0.7 ml min-1 100 ml-1 limb tissue, respectively) were about 50% to more than 100% greater (P < 0.025) than blood flow to the muscles within them (1.7 +/- 0.5 and 1.4 +/- 0.5 ml min-1 100 g-1 muscle, respectively, or 1.8 +/- 0.6 and 1.5 +/- 0.5 ml min-1 100 ml-1 muscle, respectively). In contrast, the blood flows to 100 g of forearm skin (9.1 +/- 2.6 ml min-1 100 g-1) and adipose tissue (3.8 +/- 1.1 ml min-1 100 g-1) were higher than the blood flow to 100 g of forearm (P < 0.01 and not significant, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504634 TI - Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. AB - 1. The present experiment was undertaken to investigate the influence of oral creatine supplementation, shown previously to increase the total creatine content of human skeletal muscle (Harris RC, Soderlund K, Hultman E. Clin Sci 1992; 83: 367-74), on skeletal muscle isokinetic torque and the accumulation of plasma ammonia and blood lactate during five bouts of maximal exercise. 2. Twelve subjects undertook five bouts of 30 maximal voluntary isokinetic contractions, interspersed with 1 min recovery periods, before and after 5 days of placebo (4 x 6 g of glucose/day, n = 6) or creatine (4 x 5 g of creatine plus 1 g of glucose/day, n = 6) oral supplementation. Muscle torque production and plasma ammonia and blood lactate accumulation were measured during and after exercise on each treatment. 3. No difference was seen when comparing muscle peak torque production during exercise before and after placebo ingestion. After creatine ingestion, muscle peak torque production was greater in all subjects during the final 10 contractions of exercise bout 1 (P < 0.05), throughout the whole of exercise bouts 2 (P < 0.01), 3 (P < 0.05) and 4 (P = 0.057) and during contractions 11-20 of the final exercise bout (P < 0.05), when compared with the corresponding measurements made before creatine ingestion. Plasma ammonia accumulation was lower during and after exercise after creatine ingestion. No differences were found when comparing blood lactate levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504635 TI - Sialic acids in human gastric aspirates: detection of 9-O-lactyl- and 9-O-acetyl N-acetylneuraminic acids and a decrease in total sialic acid concentration with age. AB - 1. The total sialic acid content of human gastric aspirates was measured using a colorimetric assay. Care was taken to optimize the assay and to eliminate interference. 2. The sialic acid content of gastric aspirates collected under resting conditions from 77 patients with non-ulcer dyspepsia was found to decrease with age from > 100 micrograms/ml at 25 years and younger to < 20 micrograms/ml above 70 years of age. 3. Analysis of the sialic acids by gas chromatography, mass spectrometry and thin-layer chromatography showed the presence of N-acetylneuraminic acid and two O-acylated derivatives, 9-O-acetyl- and 9-O-lactyl-N-acetylneuraminic acids. These forms were predominantly glycosidically bound. 4. Thin-layer chromatographic analysis of individual aspirate samples showed that the O-acetylated sialic acids were present in all samples, with a maximum of 25% and a minimum of 5% of the total sialic acids. PMID- 8504636 TI - Comparison of liver glutathione peroxidase activity and mRNA in female and male mice and rats. AB - 1. Female and male adult mouse and rat liver was analyzed for glutathione peroxidase activity, mRNA levels, and other selected liver enzymes. 2. Species and sex differences in liver protein, total RNA and total mRNA were minor. 3. Glutathione peroxidase activity, mRNA levels, and selenium concentration was lower in male rats when compared to female rats, male mice or female mice. 4. Plasma ceruloplasmin activity, but not liver mRNA levels, were lower in mice compared to rats. 5. Cu,Zn-superoxide dismutase activity and mRNA were not greatly influenced by species or sex. 6. Glutathione transferase activity towards 1-chloro-2,4-dinitrobenzene was highest in male mice and equivalent in the other three groups. PMID- 8504638 TI - Anionic glutathione S-transferases in shrimp eyes. AB - 1. Two anionic isoenzymes of glutathione transferases (EC 2.5.1.18), QI and QII, have been purified from the eyes of the shrimp Penaeus japonicus by using a combination of S-hexylglutathione affinity column chromatography and Mono-Q fast protein liquid chromatography (f.p.l.c.). 2. Both QI and II glutathione S transferases are homodimers. They show similarity in substrate specificities and pH optima, but not in isoelectric points. 3. QI is distinct from QII by anion exchange f.p.l.c., reverse-phase h.p.l.c. chromatography and amino acid sequencing analysis. QI has N-terminal amino acid sequences homologous to mu glutathione S-transferase, whereas QII is homologous to theta glutathione S transferases. PMID- 8504637 TI - Analysis of the subunits, isoforms and substrate specificity of mouse liver alpha L-fucosidase. AB - 1. SDS-PAGE indicates the presence of two major protein bands (57 and 62 kDa) for mouse fucosidase and Western blotting indicates that both bands are immunoreactive with polyclonal antibodies (PAbs) and/or monoclonal antibodies (MAbs) raised against human liver fucosidase. The lectins SNA and GNA recognized both mouse protein bands, indicating that both subunits are glycosylated and contain sialic acid residues. 2. Polyacrylamide gel-isoelectric focusing (PAG IEF) indicated that mouse liver fucosidase contains at least seven isoforms, with three isoforms above pI 6.0, which were not detected in human liver fucosidase. Blotting indicates that the PAbs recognized seven mouse fucosidase isoforms (pIs 3.6-6.8) whereas the four MAbs did not appear to recognize any of the mouse isoforms. 3. The subunit composition of the separated isoforms of mouse alpha-L fucosidase was investigated by SDS-PAGE. One-to-two closely-spaced protein bands are found in each isoform with a trend of increasing relative amounts of the high M(r) band in the more acidic isoforms relative to the more neutral isoforms. 4. Human and mouse liver alpha-L-fucosidases hydrolyze L-Fuc from oligosaccharides and glycolipids at comparable rates, with the exception of ganglioside Fuc-GMI which was hydrolyzed by human, but not by mouse, alpha-L-fucosidase. PMID- 8504639 TI - Different glutathione redox status and lipid peroxidation in the cortex and the medulla of the rat kidney subjected to ischemia-reperfusion stress. AB - When the rat kidney is subjected to ischemia and reperfusion, changes in glutathione content and in lipid peroxidation are produced in the cortex and in the medulla. The cortex shows a decrease in the glutathione content and a higher sensitivity to development of lipid peroxidation, the medulla being less affected. Reperfusion restores the glutathione concentration of the cortex during the first hours of reflow. The lipid peroxidation observed in the cortex and the medulla during reperfusion is higher than in ischemia. The protective role of glutathione and the response of the cortex and the medulla to ischemia reperfusion injury are discussed. PMID- 8504640 TI - pH-dependent association of carbonic anhydrase (CA) with gastric light microsomal membranes isolated from bovine abomasum. Partial characterization of membrane associated activity. AB - 1. The effect of pH on the association of carbonic anhydrase (CA) with bovine gastric light microsomal membranes (LMMs) was investigated (a) by washing LMMs containing CA activity with solutions of different pHs; (b) by studying the adsorption at various pHs of soluble bovine erythrocyte CA to washed gastric LMMs. In both cases, the association of CA with gastric LMMs was dependent on pH, being lower at neutral or alkaline pH. 2. The amount of soluble CA associated with gastric LMMs at pHs 8.0 and 9.0 was reduced when 140 mM K+/10 mM Na+ was added to the incubation medium. 3. Two sources of CA activity in bovine gastric LMMs were assumed: a loosely- and a firmly-membrane-associated activity. Both CA activities were dose-dependently inhibited by acetazolamide (I50: 3.6 x 10(-9) and 8.4 x 10(-9) M, respectively) and by chloride, acetate, iodide, bromide and nitrate at 100 mM. Firmly-membrane-associated activity appeared to be less sensitive to inhibition by acetazolamide, chloride and iodide. 4. Both activities exhibited different behavior and stability following treatment with alkaline Triton X-100. 5. The possible importance of a membrane-associated CA activity in gastric LMMs related to gastric acid secretion is discussed. PMID- 8504641 TI - Seasonal variation in the activity of 3-mercaptopyruvate sulphurtransferase of the frog (Rana temporaria) liver. AB - 1. Annual changes in the mitochondrial and cytosolic activity of MPST, GDH as a mitochondrial marker, and total protein content, were studied in frog (Rana temporaria) liver cells. 2. The variation in the MPST activity in mitochondria, regardless of the sex of the studied animals, is evidently under the influence of the thyroid gland activity, oxygen consumption and ambient temperature. 3. In the cytosol of the frog liver cells, seasonal changes of MPST specific activity seemed to be related to the production of mitochondrial iron-sulphur protein and to the protein-dependent metabolism during the fasting period. PMID- 8504642 TI - Prevention of arterial catheter failure in children--new use for an old drug? PMID- 8504643 TI - All goals are not the same. PMID- 8504644 TI - Cytokines yes, cytokines no, cytokines maybe? PMID- 8504645 TI - Predicting which preemies will fly. PMID- 8504646 TI - Management of myasthenic crisis: continuous anticholinesterase infusions. PMID- 8504647 TI - Geriatric intensive care. PMID- 8504648 TI - Double-blind, randomized, controlled trial of papaverine-containing infusions to prevent failure of arterial catheters in pediatric patients. AB - OBJECTIVE: To test the efficacy of the continuous infusion of papaverine containing fluids into peripheral arterial catheters for reducing the risk of catheter failure. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Pediatric intensive care unit in a children's hospital. PATIENTS: A total of 239 children, aged 3 wks to 18 yrs who had an arterial catheter inserted for clinical purposes. INTERVENTIONS: Patients were randomized to receive either papaverine (60 mg/500 mL) or no additive, within the infused fluids. MEASUREMENTS AND MAIN RESULTS: Data about patient demographics and potential risk factors for arterial catheter failure were collected at the time of catheter insertion, throughout the life of the catheter, and at the time of catheter removal. Catheter failure was defined as an inability to draw blood from the catheter or loss of the arterial waveform. Overall, 35 (15%) subjects had catheter failure. The risk of catheter failure was lower in patients randomized to receive papaverine (eight [7%] of 115 vs. 27 [22%] of 124; chi-square = 5.2; p = .02), and the time until failure of the catheter was longer in the papaverine group (p = .02, log-rank test). This difference persisted when controlling for potentially confounding factors. CONCLUSION: In critically ill children, infusion of papaverine-containing fluids reduces the risk of failure of peripheral arterial catheters. PMID- 8504649 TI - Effect of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study. AB - OBJECTIVE: To determine the effects of optimizing oxygen delivery (DO2) to "supranormal" levels on morbidity and mortality in patients with sepsis, septic shock, and adult respiratory distress syndrome. DESIGN: A prospective, randomized, controlled trial. SETTING: A 16-bed surgical intensive care unit (ICU) and 14-bed mixed medical/surgical ICU in two separate hospitals in the University of Hawaii Surgical and Internal Medicine Residency programs. PATIENTS: During a 1-yr period, 67 patients who had pulmonary artery catheters and who met the criteria for sepsis or septic shock, adult respiratory distress syndrome, or hypovolemic shock were enrolled in the study. Patients admitted to the ICU who were < 18 yrs old, or with a do-not-resuscitate order, or those patients who faced imminent death (< 24 hrs), such as those patients with uncontrollable hemorrhage or brain death, were excluded from the study. INTERVENTIONS: Patients were randomized into treatment and control groups. The treatment group was assigned a therapeutic DO2 indexed (DO2I) goal of > 600 mL/min/m2. Interventions to attain this goal included fluid boluses, administration of blood products, and the use of inotropes. The control group was not assigned to a specific therapeutic goal other than "normal" values of DO2I of 450 to 550 mL/min/m2. Every attempt was made to reach the therapeutic goals within the first 24 hrs after entry into the study. Hemodynamic measurements were obtained on study patients every 4 hrs until the end of the study. The severity of illness was evaluated using the Therapeutic Intervention Scoring System, and the Acute Physiology and Chronic Health Evaluation II scoring system. MEASUREMENTS AND MAIN RESULTS: There were 32 patients in the control group and 35 patients in the treatment group. The groups were similar in age, sex, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention scores. There were no statistical differences between the two groups in mortality, development of organ failure, ICU days, and hospital days. Upon analysis, it became apparent that the patients comprised clinically distinct subgroups, including: a) a treatment group who achieved supranormal DO2I; b) a control group with normal DO2I; c) a treatment group who failed to reach target DO2I; d) a control group who self-generated to high DO2I values; and e) a small number of patients who could not even reach a normal DO2I of 450 mL/min/m2. These subgroups were found to be similar and matched. The mortality rate was significantly lower for patients in groups who reached supranormal values of DO2I whether treated or self-generated as compared with patients who reached normal DO2I values (14% vs. 56%, p = .01). CONCLUSIONS: Although there was no statistically significant difference in the control vs. treatment groups, subgroup analysis demonstrated a strong, significant difference between patients with supranormal values of oxygen transport vs. patients with normal levels of DO2. Supranormal values of DO2I, whether self-generated or as a result of treatment, resulted in a statistically significant decrease in mortality rate. This study adds to the weight of evidence that current standard of care of treating critically ill patients to normal DO2I should be reconsidered, and that maximizing to high DO2I might be a more appropriate therapeutic end-point. PMID- 8504650 TI - Effects of accidental trauma on cytokine and endotoxin production. AB - OBJECTIVE: To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release. DESIGN: Prospective, multi-unit, longitudinal study. SETTING: Emergency Departments and intensive care units of two university hospitals. PATIENTS: Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL 6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL. CONCLUSIONS: These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting. PMID- 8504651 TI - A randomized, controlled trial of aminophylline in ventilatory weaning of premature infants. AB - OBJECTIVES: To determine whether maximal inspiratory force predicts successful neonatal extubation, and whether aminophylline affects maximal inspiratory force or the success rate of extubation. DESIGN: Double-blind, prospective, randomized, placebo-controlled trial. SETTING: Tertiary level neonatal intensive care unit. PATIENTS: A total of 20 ventilated, preterm, newborn infants: birth weight < 2.5 kg; gestation < 35 wks. INTERVENTIONS: Intravenous aminophylline 4 mg/kg bolus followed by 2.5 mg/kg every 6 hrs x three doses, then 1.5 mg/kg every 6 hrs; or placebo. Drug administration began when infants were receiving an FIO2 of < 0.4 and were progressively weaning from assisted mechanical ventilation. A standardized weaning protocol was instituted, and patients were extubated when they were able to tolerate a mechanical ventilatory rate of < 5 cycles/min. MEASUREMENTS AND MAIN RESULTS: Occlusion pressures, including maximal inspiratory force, were measured before aminophylline and daily until endotracheal extubation. Arterial blood gases were measured every 3 hrs, and 24-hr cardiac and respiratory recordings were performed postextubation. Three of ten aminophylline treated patients failed extubation compared with two of ten placebo infants (p = nonsignificant). Mean apnea frequency postextubation was 0.02/hr in the aminophylline group compared with 0.3/hr in the placebo group (p < .05). Aminophylline had no effect on successful extubation or on maximal inspiratory force. Maximal inspiratory force was not correlated with the success of extubation. Apnea frequency postextubation was significantly reduced by aminophylline. CONCLUSIONS: Aminophylline is an effective prophylaxis for postextubation apnea in the preterm infant but does not affect maximal inspiratory force or increase the success rate of extubation in this patient population. PMID- 8504652 TI - Postoperative utilization of critical care services by cardiac surgery: a multicenter study in the Canadian healthcare system. AB - OBJECTIVES: To describe patterns of critical care services used after cardiac surgery and to evaluate whether variations in the process of care influence outcome. DESIGN: Multicenter, prospective study. SETTING: A convenience sample of four cardiac surgical units: three in university-affiliated (teaching) hospitals and one in a nonteaching regional referral center. PATIENTS: A "consecutive sample" of 335 patients after cardiac surgery in four hospitals. INTERVENTIONS: Data were collected regarding all cardiac surgery patients admitted to the critical care units in the four test hospitals. MEASUREMENTS AND MAIN RESULTS: The critical care unit and hospital lengths of stay and survival were followed. The Therapeutic Intervention Scoring System (TISS) was used to assess the intensive care unit (ICU) interventions used during the first 24 hrs in the ICU and for the final 24 hrs before discharge from the ICU. The severity of illness on admission was assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) scoring system. For patients having similar procedures (e.g., aortocoronary bypass and nonaortocoronary bypass procedures) and with similar outcome (mortality/total hospital length of stay), we found significant differences in the pattern of ICU resource utilization among hospitals. Significant (p < .05) differences in unit length of stay were related to varying factors in different hospitals. In hospital unit A, the type of procedure and preoperative chronic health status influenced unit length of stay (aortocoronary bypass 2.8 +/- 1.7 days; nonaortocoronary bypass 8.7 +/- 8.9 days) because length of stay was different for differing procedure groups. In hospital unit B, the critical care management system and lack of step-down (intermediate care) unit availability resulted in an increased unit length of stay for aortocoronary bypass patients (5.1 +/- 4.5 days) as compared with the other units (mean ICU lengths of stay of 2.8, 2.3, and 3.0 days, respectively). Unit B kept patients for monitoring purposes and had a reduced need for critical care nursing on the day of discharge (TISS = 7.5 +/- 5.5) as compared with the other units (mean TISS scores of 27.4, 23.2, and 21.5). CONCLUSIONS: Significant differences exist among hospitals in the same healthcare system in the utilization of critical care services for cardiac surgery. In spite of these differences, for similar patient "input," the outcome (mortality and hospital lengths of stay) appeared similar. Assessments of utilization of critical care must focus on more detailed specific issues than unit length of stay, and must include factors such as availability of intermediate care areas, the unit management system, chronic health status, and the operative procedures performed, if a utilization management process is to effect improved resource use in critical care. PMID- 8504653 TI - Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit. AB - OBJECTIVE: To determine if postoperative anemia is associated with postoperative myocardial ischemia and morbid cardiac events DESIGN: Case control study. SETTING: Postanesthesia care unit and surgical intensive care unit. PATIENTS: A total of 27 high-risk patients undergoing infra-inguinal arterial bypass procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After informed consent, patients were continuously monitored by ambulatory electrocardiographic recorders from the evening before surgery up to 80 hrs during the postoperative period. Myocardial ischemia was defined as > or = 1 mm of horizontal or downsloping ST depression or > or = 2 mm ST segment elevation persisting for at least 60 secs on the ambulatory electrocardiogram. Morbid cardiac events were defined as: cardiac death, myocardial infarction, unstable angina, and ischemic pulmonary edema. Using a receiver operating characteristic curve, a hematocrit of 28% was determined to be the best threshold hematocrit value below which morbid cardiac events were most likely to occur. Statistical significance between hematocrit and cardiac outcome was determined by Fisher's exact test where appropriate. Thirteen of 27 patients had a hematocrit < 28%. Of these 13 patients, ten demonstrated postoperative myocardial ischemia and six sustained a morbid cardiac event. Of 14 patients with a hematocrit > or = 28%, two displayed myocardial ischemia and none sustained a morbid cardiac event. A hematocrit of < 28% was significantly associated with myocardial ischemia (p = .001) and morbid cardiac events (p = .0058). No significant differences in baseline heart rate and heart rate at the onset of myocardial ischemia were noted between the anemic and nonanemic patients. CONCLUSIONS: This study suggests that postoperative anemia may play a role in postoperative myocardial ischemia and cardiac morbidity. PMID- 8504654 TI - Intraocular pressure during mechanical ventilation with different levels of positive end-expiratory pressure. AB - OBJECTIVE: To determine the effect of positive end-expiratory pressure (PEEP) on intraocular pressure. DESIGN: Prospective, controlled, longitudinal, dual center study. In one group, patients served as their own control. In the second group, isolated determinations of intraocular pressure were made in mechanically ventilated patients receiving PEEP. SETTING: Adult intensive care units of two university hospitals. PATIENTS: Intraocular pressures were measured serially in eight patients during the recovery phase of different clinical conditions and in 22 patients receiving mechanical ventilation with PEEP > or = 10 cm H2O for > 24 hrs. INTERVENTIONS: Group A) In eight patients, a PEEP dose-response curve was established (PEEP 0, 5, 10, 15, and 0 cm H2O every 15 mins). Intraocular pressures were measured at the end of each period. Group B) In 22 patients, measurement of intraocular pressures were done while the patients received mechanical ventilation with PEEP > or = 10 cm H2O for at least > 24 hrs. MEASUREMENTS AND MAIN RESULTS: In both groups, there was a positive correlation between the PEEP level and the central venous pressure (p < .05 in group A, and p < .03 in group B). No relationships between intraocular pressure and PEEP or central venous pressure were observed. However, there was a correlation between intraocular pressure and length of PEEP therapy (p < .03). We found ocular hypertension in only one patient (right eye intraocular pressure = 26 mm Hg; left eye intraocular pressure = 24 mm Hg). CONCLUSIONS: Short-term therapy with PEEP of < or = 15 cm H2O does not present a clinically important significant risk for intraocular pressure increase in a population with normal basal ocular tonometry. During prolonged mechanical ventilation with PEEP, increments in intraocular pressure may occur, but these increments appear to not be of a clinically relevant magnitude. PMID- 8504655 TI - Weight changes in critically ill patients evaluated by fluid balances and impedance measurements. AB - OBJECTIVE: To study simple, rapid, and predictive methods to determine body weight changes in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Thirty-one consecutive patients. INTERVENTIONS: Calculated weight changes, using day-to-day and cumulative fluid balances corrected (in two ways) for insensible losses, were compared with the actual weight changes (mattress bascule). A tetrapolar impedance technique measuring resistance was evaluated for estimating weight changes. MEASUREMENTS AND MAIN RESULTS: No reliable relationship was found between calculated weight changes using fluid balances corrected for insensible loss and the observed weight changes. An intraindividual relationship was found between actual weight changes and changes in resistance measured with the tetrapolar impedance technique in a group of 24 critically ill patients with large weight changes (11.1 +/- 6.7 kg). No such intraindividual relationship was found in seven patients with small weight changes (3.1 +/- 2.2 kg). In each patient, the slope coefficient of the change in weight and resistance relationship differed; this individual slope coefficient could be an indication for hydration. CONCLUSIONS: Calculated fluid balances are not predictive for actual weight changes in critically ill patients. Absolute weight measurements are indispensable. Changes in resistance correlated with weight changes in individual patients if weight changes were > 3 kg. PMID- 8504656 TI - Simultaneous radial, femoral, and aortic arterial pressures during human cardiopulmonary resuscitation. AB - OBJECTIVE: To examine the validity of interchanging arterial sites and their responses to graded doses of epinephrine during human cardiopulmonary resuscitation (CPR). DESIGN: Consecutive case series. SETTING: Large, urban Emergency Department. PATIENTS: Adult, normothermic, nonhemorrhagic cardiac arrest patients. INTERVENTIONS: While receiving advanced cardiac life support, patients received right atrial (n = 40), aortic (n = 40), radial (n = 40), and femoral (n = 17) artery catheters. Pressures were measured simultaneously at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine. MEASUREMENTS AND MAIN RESULTS: The mean aortic compression-phase pressure was 9.3 +/- 10 (SD), 8.1 +/- 11, and 4.4 +/- 9.5 mm Hg higher than radial artery pressure at baseline, after 0.01 mg/kg, and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the mean aortic compression-phase pressure was also 3.0 +/- 6.8, 1.9 +/- 8, and 0.6 +/- 7.7 mm Hg higher, respectively (none statistically significant). The aortic relaxation-phase pressure was 1.3 +/- 3.6, 1.1 +/- 3.8, and 1.6 +/- 2.5 mm Hg lower than the radial artery at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the aortic relaxation-phase pressure was 0.6 +/- 2.0, 0.3 +/- 3.3, and 0.3 +/- 2.4 mm Hg lower, respectively (none statistically significant). CONCLUSIONS: Radial artery relaxation-phase pressure, although statistically higher, correlated with aortic relaxation-phase pressure. Femoral artery relaxation-phase pressure was not statistically different from aortic relaxation-phase pressure. Aortic pressure was statistically higher and had a lower correlation with radial artery pressures during compression phase. The aortic to radial artery and aortic to femoral artery compression-phase gradients abated with increasing doses of epinephrine therapy. Caution must be used when substituting compression-phase pressure obtained at radial or femoral artery sites for aortic pressure during human CPR. Coronary artery perfusion pressures obtained with radial and femoral arteries correlate with aortic pressure when measuring the response to vasopressor therapy during CPR when an interpretable waveform exists. PMID- 8504657 TI - Metabolic alkalosis in children undergoing cardiac surgery. AB - OBJECTIVE: To define the frequency of metabolic alkalosis and its pathogenesis in children after open-heart surgery. DESIGN: Retrospective chart review. SETTING: Multidisciplinary, tertiary, pediatric intensive care unit. PATIENTS: Fifty-six consecutive children undergoing open-heart surgery. MEASUREMENTS AND MAIN RESULTS: Metabolic alkalosis occurred in 29 (52%) of 56 patients. Seventy-two percent of patients < 12 months of age developed metabolic alkalosis as compared with 30% of patients > 12 months of age (p < .01 by chi-square). Patients developing metabolic alkalosis were younger, received more furosemide, had lower serum chloride concentrations, and underwent longer cardiopulmonary bypass times than nonmetabolic alkalosis patients. By stepwise multiple linear regression analysis, only age (p < .05) and serum chloride concentrations (p < .001) had independent correlations with the development of metabolic alkalosis; both variables had inverse correlations with arterial pH (r2 = .42). Patients with metabolic alkalosis also developed significantly (p < .01 by two tailed Student's t-test) lower serum ionized calcium concentrations (4.2 +/- 0.5 mg/dL [1.05 mmol/L]) as compared with nonmetabolic alkalosis patients (4.6 +/- 0.4 mg/dL [1.15 mmol/L]). CONCLUSIONS: Postoperative metabolic alkalosis occurs frequently in children undergoing open-heart surgery. Chloride depletion seems to be the predominant factor in the pathogenesis of metabolic alkalosis. Younger age can serve as a positive predictor for the development of metabolic alkalosis in this subset of patients. PMID- 8504658 TI - Exaggerated cardiopulmonary response after bacteremia in sheep with week-old thermal injury. AB - OBJECTIVE: To determine if thermal injury impairs pulmonary intravascular clearance of bacteria and therefore leads to exaggerated cardiopulmonary dysfunction in sheep, since endotoxin infusion has been previously shown to induce more severe pulmonary injury after thermal injury. DESIGN: Prospective, unblinded, randomized, controlled trial. SETTING: Laboratory at a large university medical center. INTERVENTIONS: Chronically instrumented, anesthetized sheep received a 40% total body surface area, third-degree thermal injury. Live Pseudomonas aeruginosa (10(7) P. aeruginosa/min for 1 hr; n = 6) were infused 7 to 10 days after thermal injury. Similarly prepared noninjured sheep received the same pseudomonas infusion (n = 7) or saline (n = 7). MEASUREMENTS AND MAIN RESULTS: Bacterial clearance, which measures phagocytosis by the pulmonary intravascular macrophages, was equally efficient in intact sheep and sheep with thermal injury. Pulmonary hypertension persisted for 18 hrs after thermal injury, compared with 8 hrs in noninjured sheep. Lung lymph flow significantly increased from 6 to 8 hrs in only the thermal injury group. Both bacteremic groups developed a hyperdynamic circulation from 6 to 8 hrs, but cardiac index was 1 to 1.5 L/min/m2 higher in thermally injured sheep. Total peripheral resistance index decreased significantly from 6 to 24 hrs in thermally injured sheep and from 6 to 12 hrs in intact bacteremic sheep. Mean arterial pressure of thermally injured sheep was increased at baseline and for the first 6 hrs compared with noninjured animals. Mean arterial pressure decreased from 6 to 24 hrs in sheep with thermal injury but did not change in intact bacteremic sheep. CONCLUSIONS: Bacterial clearance was not impaired by preceding thermal injury in sheep. Bacteremia in the presence of a preexisting thermal injury led to more persistent pulmonary hypertension and an exaggerated hyperdynamic circulation. PMID- 8504659 TI - Relationship between liver oxidant stress and antioxidant activity after zymosan peritonitis in the rat. AB - OBJECTIVE: To determine the effect of a severe nonbacterial-dependent peritonitis on the degree and time course of liver oxidant stress and antioxidant activity. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory. SUBJECTS: Thirty-eight male Sprague-Dawley rats were injected with zymosan 0.75 mg/g body weight, mixed in mineral oil, and fluid resuscitated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2), base deficit, and blood gases were determined. Liver tissue oxidized and reduced glutathione, malondialdehyde catalase, xanthine oxidase, and xanthine dehydrogenase were measured and data were compared with both a pair-fed and an ad libitum fed group over a 24-hr period. We noted a 30% mortality rate with animals dying between 20 and 24 hrs. Peak decrease in VO2 occurred at 12 hrs, corresponding with a metabolic acidosis. Marked liver oxidant stress was seen at 4 hrs with oxidized glutathione increased from a control value of 0.2 +/- 0.1 to 1.1 +/- 0.2 mg/g of tissue, while reduced glutathione decreased from a control value of 1.8 +/- 0.1 to 0.3 +/- 0.1 mg/g. By 24 hrs, oxidized glutathione activity was no longer increased, but reduced glutathione concentrations were still markedly decreased. Tissue catalase was also significantly decreased at the 24-hr period. Liver malondialdehyde was increased at 24 hrs when the peak decrease in antioxidants was evident. Liver xanthine oxidase activity increased significantly from 15 +/- 3 to 45 +/- 8 mumol uric acid/min/g by 4 hrs and remained increased, with the initial increase predating evidence of impaired perfusion. Pair-fed animals demonstrated no changes in oxidant or antioxidant activity. CONCLUSIONS: We conclude that a marked increase in liver oxidant stress and decrease in antioxidant activity occurs in the first several hours after the onset of nonbacterial peritonitis. An early increase in liver xanthine oxidase activity may be a source of the oxidants. Decreased liver antioxidant activity persists well after the oxidant stress resolves. PMID- 8504660 TI - Intramyocardial hypercarbic acidosis during cardiac arrest and resuscitation. AB - OBJECTIVE: To define changes in intramyocardial pH and PCO2 during cardiac arrest and resuscitation. DESIGN: Prospective and observational trial. SETTING: Mammalian research laboratory utilizing a porcine model of cardiac arrest. SUBJECTS: Sixteen domestic pigs. INTERVENTIONS: Ventricular fibrillation was induced by an alternating current delivered to the epicardium. Precordial compression was begun after 3 mins of untreated cardiac arrest and was initially adjusted to produce a coronary perfusion pressure of 10 mm Hg. Electrical defibrillation was attempted after an additional 8 mins of precordial compression. MEASUREMENTS AND MAIN RESULTS: A rapid-response, ion-selective field effect transistor sensor was adapted for measurement of intramyocardial PCO2. Intramyocardial PCO2 progressively increased from 54 to 346 torr (7.2 to 46.1 kPa) during the 11-min interval of cardiac arrest. Intramyocardial hydrogen ion concentrations were simultaneously measured with a glass electrode. The intramyocardial hydrogen ion value increased from 65 nmol/L (pH 7.20) to 441 nmol/L (pH 6.38) over the same interval. The increases in myocardial PCO2 were inversely correlated with coronary perfusion pressure and with the likelihood of successful resuscitation. Within 30 mins after successful cardiac resuscitation, myocardial PCO2 had almost completely returned to prearrest levels. CONCLUSIONS: Striking increases in myocardial PCO2 and hydrogen ion values accompany the global myocardial ischemia of cardiac arrest. The increases in myocardial PCO2, rather than decreases in pH, reflected more precisely the hemodynamic efficacy of the resuscitation effort, correlated inversely with coronary perfusion pressure, and predicted the likelihood of successful resuscitation. PMID- 8504661 TI - Influence of hypoxic and hypercapnic acidosis on brain water content after forebrain ischemia in the rat. AB - OBJECTIVE: To determine whether hypoxia or hypercapnia superimposed on ischemia affects brain water content after ischemia. DESIGN: Prospective, randomized, controlled trial. SUBJECTS: Thirty-one male Wistar rats. INTERVENTIONS: The rats were assigned randomly into one of six groups: a) control; b) ischemia; c) ischemia combined with hypoxia; d) ischemia combined with hypercapnia; e) hypoxia; f) hypercapnia. Forebrain ischemia was induced for 5 mins by clamping both carotid arteries and inducing exsanguination. Either hypoxia or hypercapnia was induced until the arterial pH decreased to 7.0. The rats were decapitated after the protocol. MEASUREMENTS AND MAIN RESULTS: After the decapitation, the specific gravities of the neocortex, caudatoputamen, hippocampus, cerebellum, and midbrain were measured using a variable-density bromobenzene-kerosene column technique as an index of brain swelling. The specific gravities of the hippocampus and the neocortex were significantly lower in the ischemic group than in the control group. Specific gravities of the caudatoputamen and neocortex in the ischemia plus hypercapnia group, and specific gravities of the caudatoputamen, neocortex, and hippocampus in the ischemia plus hypercapnia group, were significantly lower than in the ischemia group. CONCLUSIONS: Cerebral water content increases more when ischemia is accompanied by hypoxia or hypercapnia than after ischemia alone. Hypoxic and/or hypercapnic acidosis during the periresuscitation period may be one of the causes of brain swelling after the resuscitation of patients after an anoxic-ischemic insult. PMID- 8504662 TI - Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine. AB - OBJECTIVES: The goals of this study were: a) to evaluate the efficacy of controlled, continuous arteriovenous hemofiltration in improving morbidity and mortality rates in an immature swine model of Staphylococcus aureus-induced septicemia; b) to determine if ultrafiltrate from septic animals contained mediators that produce pathophysiologic changes observed in untreated S. aureus septic pigs. DESIGN: Prospective, randomized, controlled study with age-matched controls. SETTING: U.S. Department of Agriculture-licensed biomedical research facility. SUBJECTS: Sixty-five weaned Poland-China swine (4 to 6 wks of age; 5 to 10 kg). INTERVENTIONS: Part 1: Animals received a lethal dose of live S. aureus (8 x 10(9) colony-forming units/kg) over 1 hr. The three treatment groups included: hemofiltration group 1 (eight filtered, eight nonfiltered animals), plasma filtration fraction = 5.5%; hemofiltration group 2 (six filtered, six nonfiltered animals), filtration fraction = 16.6%; and hemofiltration group 3 (six filtered, six nonfiltered animals), filtration fraction = 33.4%. A control, nonseptic group of animals (n = 4) was filtered to obtain "clean" ultrafiltrate (hemofiltration group 4). Part 2: Sterile ultrafiltrate concentrate batches obtained from each group of filtered, septic animals were concentrated and infused into healthy, nonseptic pigs (reinfusion groups 1 through 3). MEASUREMENTS AND MAIN RESULTS: Physiologic, biochemical, and hematologic variables were measured in all animals every 1 to 3 hrs. Overall length of survival was also recorded. In hemofiltration groups 1 through 3, filtered animals survived significantly longer than matched, nonfiltered (sham-filtered) animals. Increments in survival time increased directly with filtration fraction. Ultrafiltrate concentrate from septic pigs produced death (LD41) and disease similar to those rates observed in untreated S. aureus-septic pigs. Infusion of clean ultrafiltrate concentrate produced no response. CONCLUSIONS: Continuous arteriovenous hemofiltration significantly improved survival rates in swine with S. aureus-induced sepsis. Resultant ultrafiltrate concentrate contained mediators responsible for some pathophysiologic responses observed in this animal model. PMID- 8504663 TI - Continuous infusion of pyridostigmine in the management of myasthenic crisis. PMID- 8504664 TI - Tension pneumoperitoneum as a complication of barotrauma. PMID- 8504665 TI - Permissive hypercapnia and pressure-controlled ventilation as treatment of severe adult respiratory distress syndrome in a pediatric burn patient. PMID- 8504666 TI - Low relative humidity delivered by a humidifier with a heating wire. PMID- 8504667 TI - Jail suicide--prevention through written protocol (Part 1) PMID- 8504668 TI - Hotlines--legal issues. PMID- 8504669 TI - Adolescent grief after suicide. AB - After suicide of a loved one, adolescents may develop emotional problems and depression, and are at increased risk of suicide. They thus constitute a major population in need of counseling. Age, social support, development tasks, and death concepts determine how adolescents react to the experience of grief. Suicide changes the bereaved adolescent's role, identity, expectations, and daily activities, and may heighten anxiety about whether life is worthwhile. PMID- 8504670 TI - Panic disorders and suicidal behavior. PMID- 8504671 TI - The social transmission of parasuicide: is there a modeling effect? AB - This article examines four hypotheses derived from social learning theory about the social transmission of parasuicide. The first of these, that parasuicides will have significantly more prior contact with suicidal behavior than matched general population controls, was tested using the Contact with Suicidal Behavior Schedule. There was a tendency for more controls than parasuicides to report nonintensive contact, although more parasuicides claimed intensive recent contact. Overall, lifetime contact did not differ between groups. The second hypothesis suggested that parasuicides who repeat the act will have significantly more prior contact with suicidal behavior. Support for this was almost wholly lacking. The third and fourth hypotheses concerned the relationship between prior contact and attitudes towards parasuicide (using the Case Vignette Instrument). The bulk of the evidence suggested, contrary to predictions, that more contact was associated with more unfavorable attitudes. It was concluded that empirical support in this study for the existence of a modeling effect in parasuicide was, at best, somewhat weak. PMID- 8504672 TI - Attempted suicide, suicidal intent, and alcohol. AB - The purpose of the present study was to relate suicidal intent to the suicide method chosen and the medical lethality of the suicidal act, and to discuss how ingestion of alcohol impacts these three factors. The study was based upon interviews with 139 suicidal patients admitted to the Department of Psychiatry of Odense University Hospital. The results indicated a tendency for suicide attempters using wrist-cutting to score low on the Suicidal Intent Scale. Patients using kinds of self-injury other than self-poisoning or wrist-cutting scored high. In the case of self-poisoning, suicidal intent did not influence the choice of toxic agent, nor was the choice of method and/or choice of toxic agent affected by alcohol ingestion. A correlation between suicidal intent and the lethality of the suicide attempt was seen only among patients without a diagnosis of alcohol dependence. Alcohol-dependent patients who made highly lethal attempts scored relatively low on the Suicidal Intent Scale. The results indicate that the lethality of the suicidal act is only an incomplete guide to a patient's suicidal intent. However, it should be stressed that, despite the fact that alcohol dependent suicide attempters may not strongly wish to die, they are nonetheless at high risk for making fatal suicide attempts. PMID- 8504673 TI - Deliberate self-harm and public holidays: is there a link? AB - It has previously been reported [Davenport & Birtle, 1990] that there is a positive association between nonfatal deliberate self-harm in adolescents and emotionally charged festivals, such as St Valentine's Day and Christmas Day. We studied all cases of nonfatal deliberate self-harm presenting to three Central London hospitals on St Valentine's Day and Christmas Day and on two control dates, between 1983 and 1989. No association was found between cases of deliberate self-harm and St Valentine's Day, but a negative association was found with Christmas Day. PMID- 8504674 TI - Suicide pacts. AB - Suicide pacts in an Indian population were studied through police records of the state of Tamul Nadu. A total of 148 suicide pacts, involving 324 persons, were identified. More women died in them than might be expected from general population figures. Social stressors like financial problems and marriage-related issues were the principal causes. The results and their implications are discussed and compared with those obtained in Western and other Eastern countries. PMID- 8504675 TI - Suicide in the elderly: when is it rational? PMID- 8504676 TI - Critical care unit family support sessions: using postvention principles in a medical setting. PMID- 8504677 TI - Effects of intentional hemodilution on pulmonary stasis and edema in patients and experimental animals. AB - The therapeutic effects of intentional hemodilution (IHD) on 64 patients of rheumatic mitral valvular disease with chronic pulmonary stasis were estimated. The mean hematocrit was decreased from 0.50 +/- 0.06 to 0.41 +/- 0.04 by withdrawing blood and replacing it with diluent. The whole blood ratio viscosity was decreased from 11.7 +/- 2.4 to 6.4 +/- 0.8 (P < 0.01), the pulmonary arterial pressure was reduced from 6.4 +/- 0.6 to 4.1 +/- 0.5 kPa (0.133 kPa = 1 mmHg) (P < 0.01), the pulmonary vascular resistance brought down from 536.0 +/- 108.0 to 315.0 +/- 62.0 dynes.s.cm-5 (P < 0.01), the cardiac output increased from 3.4 +/- 0.4 to 5.6 +/- 0.5 L/min (P < 0.01), the cardiac index increased from 2.2 +/- 0.5 to 3.5 +/- 0.4 L/min/m2 (P < 0.01), and venous oxygen saturation and oxygen content increased from 28.5 +/- 3.4%, 5.1 +/- 0.5% to 56.0 +/- 5.0%, 11.3 +/- 1.2%, respectively (P < 0.01). The patients' symptoms and signs improved significantly. The protective role of IHD in the early stage of lethal pulmonary edema induced by epinephrine in 39 rabbits and 27 rats was also observed. The experimental data show that intentional hemodilution increased the animals' survival rate (P < 0.01), reduced the pulmonary coefficient, permeability index of Evans blue and protein content in broncho-alveolar lavage fluid (BALF) (all P < 0.01), and alleviated the pathomorphological changes of the lungs of animals in Group IHD were alleviated. The results suggest that IHD acts well in both chronic pulmonary stasis and acute pulmonary edema. PMID- 8504678 TI - Postoperative pulmonary tissue changes following autogenous lung and artificial lung bypass. Comparative studies. AB - With regard to pulmonary tissue damage secondary to extracorporeal circulation, most studies focused on the pulmonary histological changes after artificial lung bypass, but none compared the pre- and post-operative pulmonary changes of artificial lung with those of autogenous lung. We compared the changes in autogenous lung oxygenation and artificial lung oxygenation during cardiopulmonary bypass (CPB). The results showed that autogenous lung oxygenation is less injurious to the lung than bubble oxygenation and is more physiological. We think that during open heart surgery with autogenous lung bypass, the lung is functioning physiologically and supplied with normal amount of oxygen, while using bubble oxygenation for CPB, the native lung, the only nonperfused organ, is insulted by pulmonary ischemia, which is one of the most important reasons for pulmonary injury after CPB. PMID- 8504679 TI - Cloning of a DNA probe and its application in the detection of Plasmodium falciparum. A preliminary report. AB - The clones containing parasite DNA fragments were screened from a genomic DNA library of Plasmodium falciparum FCC1/HN isolate. A DNA probe derived from clone pBF4 consisting of 3 kilobase pairs hybridizes specifically with P. falciparum DNA but not with human DNA, P. cynomolgi DNA or P. berghei DNA. The nick translated radiolabelled probe can detect 10 pg purified P. falciparum DNA and a 0.001% parasitemia after 24 hours of film exposure. The probe reacts with all microscopically diagnosed P. falciparum samples and 3 of 41 P. vivax samples as well but not with any of 10 human DNA samples. PMID- 8504680 TI - Somatosensory evoked potentials in patients with cerebral hemorrhage and infarct. Correlation with CT, clinical data and their prognostic significance on limb function. AB - Somatosensory evoked potentials (SEP) arising from median nerve stimulation were recorded in 102 patients with unilateral cerebral hemorrhage or infarct located in basal ganglion, internal capsule, thalamus or cerebral lobe. Of them 42 cases were followed up and reexamined with SEPs. Three types of SEPs were observed: 1) absence of all SEPs components, 39 cases; 2) slight to moderate abnormalities of SEPs, 37 cases; 3) symmetric and normal SEPs, 26 cases. The total abnormal rate of SEPs was 76.5%. There were no definite correlations between abnormal SEPs and lesion location, size and lesion nature. The diagnosis of cerebral vascular disease might be obtained more directly and precisely by CT scan than by SEPs. However, SEPs may serve as an objective neurophysiologic means in assessing the neurological function of the affected limb, in which their abnormalities and severity are of great value to evaluate the probability and the degree of sensorimotor functional rehabilitation of the limb. When SEPs are absent, the recovery of the limb functions may be very poor no matter whether it is hemorrhage or infarct regardless of its lesion size and location. PMID- 8504681 TI - Hemodynamic evaluation of bovine pericardial xenograft valves in the mitral position by stress Doppler echocardiography. AB - The function of a bovine pericardial xenograft valve in the mitral position was studied in 18 patients by using stress Doppler echocardiography after submaximal supine exercise. In 10 patients with normally functioning tissue valve, peak and mean gradients increased from 9.3 +/- 1.3 and 2.7 +/- 0.7 mmHg, respectively at rest, to 14.7 +/- 0.9 and 4.1 +/- 1.0 mmHg at peak exercise. The tissue valve area assessed by the Doppler pressure half-time method increased from 2.69 +/- 0.38 cm2 at rest, to 3.15 +/- 0.38 cm2 at peak exercise (P < 0.05). In 6 patients with mitral regurgitation, peak and mean gradients increased from 17.3 +/- 5.3 and 7.0 +/- 1.8 mmHg, respectively at rest, to 24.3 +/- 5.0 and 9.0 +/- 2.6 mmHg at peak exercise, but there was no significant change in valve area at peak exercise. Patients with severe isolated mitral regurgitation had a Vmax of more than 2 m/s and elevated pressure gradients at peak exercise. But the pressure half-time was relatively unaffected, allowing their differentiation from patients with tissue valvular stenosis. Stress Doppler echocardiography is a simple, noninvasive and reliable method for the evaluation of the mitral tissue valve function which is recommendable for patients with suspected mitral tissue valve dysfunction. PMID- 8504682 TI - Structure and pathogenesis of plexiform lesion in pulmonary hypertension. AB - Plexiform lesions are a characteristic vascular change of pulmonary arteries in pulmonary hypertension. Autopsy of lungs from 28 patients with primary pulmonary hypertension were examined to clarify the nature of the plexiform lesions. Histological studies showed that the plexiform lesions, were usually related to fibrous occlusion at the peripheral sites of pulmonary arteries. To clarify the topographic correlation between the arterial occlusion and plexiform lesions a three dimensional analysis of the pulmonary arteries was performed with a computerized image analyzer. The plexiform lesions were located in the small supernumerary branches which were raised at more proximal sites than the occlusive lesions of their parent pulmonary arteries. An electron microscopic study demonstrated that the arterial branches were severely injured and developed into aneurysm-like dilatation with organization. Within the organized arterial branches, endothelial cells proliferated to form complicated capillary-like channels, which is a feature of the plexiform lesion. From these findings the following process may be considered in pulmonary hypertension: the occlusive changes of peripheral pulmonary arteries may induce a by-pass in the proximal supernumerary branches which are severely affected by increased shear stress and ultimately organized. As a result of the organizing, proliferation of endothelial cells may produce plexiform lesions in the special branches of pulmonary arteries. PMID- 8504683 TI - Blood levels of sex hormone in lupus nephritis and their relationship to lupus activity. AB - One hundred and fifty-nine patients (140 females, 19 males) with lupus nephritis (LN) were studied. Renal biopsy was performed for each patient with light microscopy, immunofluorescence and electronic microscopic studies. 27 normal subjects were selected as controls. Blood levels of sex hormone including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and testosterone (T) were measured by radioimmunoassay (RIA), and some clinical, laboratory and histological parameters were collected for analysis of lupus activity. It was found that serum FSH, LH and plasma E2 of all patients were much higher than normal (P < 0.01) while plasma T was much lower in female patients (P < 0.01) but normal in male patients. The lupus activity was proved to be closely related to plasma E2 and T (P < 0.05). There was no definite relationship between abnormal plasma E2 or T and serum IgG, C3 C4, ANA, A-dsDNA or A-Sm. The levels of sex hormones among every histological type of LN were not significantly different. It was concluded that: 1. The increment of plasma E2 is associated with lupus activity in both male and female patients. 2. The decrement of plasma T only in female patients is also related to lupus activity. 3. No relationship could be found among FSH, LH, E2 and T. PMID- 8504684 TI - William D. Sawyer, M.D. has been cordially invited to be a member of the Advisory Board of the Chinese Medical Journal. PMID- 8504685 TI - Hook-pin and compression screw in the treatment of femoral neck fractures. Clinical trial and biomechanical study. AB - One hundred and two patients with femoral neck fracture underwent combined hook pin and compression screw fixation. Eighty-five patients were followed up for over 6 months. The fracture was united in 80 patients. The advantages of this method included less trauma, simple technique and firm internal fixation and early postoperative partial weight-bearing. Biomechanical study showed that this method is superior to Smith-Petersen nailing and two hook-pins methods. The sliding and continuous compression of this method promotes impaction and healing of the fracture. PMID- 8504686 TI - Etiopathological investigation of Mooren's ulcer. AB - Using the indirect immunofluorescence test (IFT), the authors examined the sera of 16 patients with Mooren's ulcer for the presence of antibodies against normal rabbit and human corneal epithelial cells, and determined the percentages of T lymphocyte subsets in the peripheral blood of the patients and controls. The results indicate that (1) serum antibodies against rabbit corneal epithelial cells were positive in 75% of the patients, serum antibodies against human corneal epithelial cells were positive in 37.5%, whereas in 20 normal controls the above serum antibody against both were negative; (2) the percentage of OKT8+ in patients was significantly lower and the OKT4+/OKT8+ ratio significantly higher than those in the controls (P < 0.01). The etiopathogenesis of Mooren's ulcer is discussed and the authors especially point out that regulatory imbalances exist in the patient's immune systems and Mooren's ulcer is an autoimmunological eye disease. PMID- 8504687 TI - Assessment of Nd:YAG laser via metal cap and sapphire tip delivery system. An experimental and clinical investigation. AB - Sixteen segments of normal human aorta were irradiated by Nd:YAG laser beam delivered via domestically made metal cap and sapphire tip fibre systems. It was found that the metal tip fibre caused more target tissue damage and adhesion than the sapphire tip fibre. The sapphire tip fibre caused an ablation crater with a smoother edge, less carbonization layer and smaller thermal necrotic zone than the metal tip did. The metal cap and sapphire tip fibre were applied to 2 cases of iliac artery stenosis and 5 cases of coronary stenosis, all showing an immediate ablation. PMID- 8504688 TI - Present status of cataract surgery and intraocular lens in China. PMID- 8504689 TI - Surgical treatment of atherosclerotic infrarenal abdominal aortic aneurysms. A review of 30 years' experience. AB - During the 30 years from 1960 to 1989, 100 sequential patients with atherosclerotic infrarenal abdominal aortic aneurysm (AAA) were admitted to Zhongshan Hospital. Twenty-eight were not treated surgically and 72 underwent resection of the AAA with prosthesis replacement. Nineteen non-surgical patient were followed up, and 8 died from ruptures with a five-year survival rate of 41.3 +/- 13%. In 72 surgically treated patients, the operative mortality was 2.8%. The five-year survival rate is 77.5 +/- 6.2%, which is higher in comparison with the non-surgical group (P < 0.01). The data show that the operation for AAA is safe and the postoperative long-term results are satisfactory. PMID- 8504690 TI - Hepatitis B virus DNA detected by PCR in sera and liver tissues of Chinese patients with chronic liver diseases. AB - To investigate the HBV infection and its replication in Chinese patients with chronic liver disease, polymerase chain reaction (PCR) was employed to detect hepatitis B virus DNA in sera of 410 patients with chronic liver disease and liver samples from 188 patients. The HBV DNA detectability in all serum samples was 58%. Among them 100% HBeAg-positive and 58% anti-HBe cases were HBV DNA detectable respectively. However, HBV DNA was also found in 23% HBsAg negative/anti-HBc positive chronic cases. Furthermore, 30% anti-HBs positive chronic cases who had neutralizing antibody against HBV infection, continued to contain HBV DNA. Our findings indicate that HBV infection and its replication are dominant cause of chronic liver disease and some HBV variants may escape from the protective antibody to induce chronic liver disease, even anti-HBs antibody circulated. PMID- 8504691 TI - Changes of polymorphonuclear leukocyte membrane fluidity in patients with viral hepatitis. PMID- 8504693 TI - Lipoperoxidative damage in experimental rabbits with atherosclerosis. AB - The extent of lipoperoxidation in experimental rabbits with atherosclerosis was determined dynamically during the experimental period of 65 days. Lipoperoxide (LPO) levels and selenium-dependent glutathions peroxidase (SeGSHPx) activities in liver, aorta, heart muscle, plasma erythrocyte (RBC) and platelet were examined on the 65th day. The results showed that the potential anti lipoperoxidation in the atherosclerotic rabbits was decreased significantly, and the tissues were suffered from lipoperoxidative damage. It seems that there is a close relationship between lipoperoxidative damage and the development of atherosclerosis. PMID- 8504692 TI - Countercurrent immunoelectrophoresis for diagnosis of acute bacterial pneumonia in Chinese children. AB - Countercurrent immunoelectrophoresis (CIE) with H. influenzal type b(Hib) and Pneumococci Omni antisera was performed on serum and concentrated urine and pleural fluid samples from 100 patients with acute pneumonia in Beijing Children's Hospital. Thirty-one patients were investigated by bacteriologic techniques (blood culture and pleural fluid culture). CIE was positive in 29/100 (29%) of cases of Hib, 13/100 (13%) of cases for pneumococci. Overall, bacterial causes of pneumonia were diagnosed by CIE in 41/100 (41%) cases. Antigens were detected in 5/90 (5.6%) serum samples, in 36/87 (41.5%) concentrated urine samples, and in 1/2 (50%) samples of pleural fluid. Only one Hib strain was found by pleural fluid culture. The contamination rate of bacterial culture in this group was high (5/31 cases, 16.1%). Therefore, traditional bacteriologic techniques are of very limited value for diagnosing pneumonia in Chinese children. The results showed that bacterial pathogen, especially Hib and Pneumococci, are very common and important causes of pediatric pneumonia in China. PMID- 8504694 TI - Techniques for isolating hair cells from guinea pig cochlea. AB - Isolated live hair cells are important models for studies on the electrophysiology, pathology and pharmacology of the hair cell. Using mechanical isolation method after papain treatment, 70 +/- 27 hair cells, including 0 to 4 inner hair cells, could be obtained from each cochlea of 4 guinea pigs. The criteria for a good viability of isolated cochlear hair cells were: 1) a smooth hair cell membrane; 2) hair cells not swollen; 3) the nucleus in normal position; 4) the cytoplasm in a state of translucence with a halo at the periphery (birefringence); and 5) no Brownian movement of the organelles within the cytoplasm. With short-term culturing at room temperature, approximately 90% of the isolated hair cells retained a good viability at the end of two hours. Subsequently, the hair cells gradually degenerated but still, at the end of five hours, about 40% of them appeared intact. The degeneration patterns have been carefully observed and described. PMID- 8504695 TI - Ion-exchange chromatography in simultaneous determination of serum copper and zinc levels in patients with cancer of digestive tract. AB - Serum copper and zinc were simultaneously determined by ion-exchange chromatography (IC) in 35 normal volunteers and 45 patients with benign diseases or different stage cancers of digestive tract. No significant differences of serum Cu, Zn (both expressed in mumol/L) and Cu/Zn ratio were found among normal volunteers, patients with benign diseases and those with stage I or II cancer. While in the group of stage III and IV cancer patients, the mean of serum Cu (26.5 +/- 1.4 mumol/L) and Cu/Zn ratio (2.25 +/- 0.16) increased significantly (P < 0.01) and that of serum Zn (11.8 +/- 0.5 mumol/L) decreased markedly (P < 0.05). Our results showed that serum Cu, Zn and Cu/Zn ratio was of no help in detecting early stage cancers and in differentiating them from benign diseases but was useful in predicting stages of cancers before operation for a better choice of therapy. PMID- 8504696 TI - Stress analyses after femoral shaft osteotomy fixed by various plates with different rigidities in simulation test. AB - Three pairs of human cadaver femora were used for strain measurement under a weight-bearing simulation test, which was performed on intact bone and osteotomized bone fixed by 3 types of plates with different rigidities respectively. The plates with uniform thickness did not adhere to the uniform stress distribution along the plate. The stress between both central screw holes was significantly great. However, the device of trapezoidal plate conformed to the uniform stress distribution along it, and the safety factors of 3 different types of the plates were proposed. The osteotomy site was mainly subjected to compression stress in standing phase with load on both femora, but subjected to bending stress mostly with load on the single femur. The total compression strain at the osteotomy site was greater than that on intact bone while the load was adding over twice body weight with load on both legs, and nearly normal with load on one leg. We believe that the bone structural changes caused by stress shielding and limb disuse etc can be overcome by using optimal plate and normal weight bearing. PMID- 8504697 TI - Association between HLA antigens and families with psoriasis vulgaris. AB - This paper typed HLA-A, B, C and DR antigens in patients with psoriasis vulgaris and healthy persons in 12 families. The phenotype frequencies of HLA-A1, B13, B17, Cw4 and Cw6 in the patients were higher than those in the controls. The analysis of haplotype segregation showed that HLA haplotypes in families with more psoriatic cases were marked deviation from random distribution. One or two HLA haplotypes sharing among affected siblings occurred more frequently than expected. The result of Lods score for six families showed that there was a close linkage between the gene of psoriasis vulgaris and HLA antigens. The gene of psoriasis was coincided with the recessive hereditary mode. PMID- 8504698 TI - Ultrasonic studies of the effect of artemisia decoction on the volume and dynamics of gallbladder. AB - This paper deals with the ultrasonic studies of the effect of artemisia decoction (AD) on the volume and motion of gallbladder in 33 cases. Ultrasonic examination shows that AD intravenous infusion has remarkable effects on the contractility of gallbladder. There are 4 patterns of phasic changes in the motion of gallbladder and an increase in frequency of its contraction and relaxation. AD has also certain contraction effects on the gallbladders which can not contract after a fatty meal. The above findings indicate that AD is a good choleretic and has a definite regulating effect on the motility of the gallbladder. The clinical use of AD is conducive to bile flow, stone expelling, inhibiting the deposition of bile solids and reducing the possibility of stone formation. PMID- 8504699 TI - A case of Hallervorden-Spatz syndrome diagnosed antemortemly. AB - A sporadic case of Hallervorden-Spatz Syndrome was diagnosed before death. The diagnosis was made on clinical manifestations and histopathology of the tissue fragments obtained from the globus pallidus by stereotaxic brain biopsy. The involvement of thoracolumbar spinal cord is discussed. The cranial computed tomography showed caudate atrophy with bicaudate index (CC/OTcc) of 0.2, and the quotient FH/CC of 1.43, which were indistinguishable from Huntington's disease. PMID- 8504700 TI - Five-year follow-up of immune response to hepatitis B vaccine in juveniles. AB - The persistence of anti-HBs was investigated in 95 juveniles who received plasma derived HBV vaccine (vaccine group) and 63 counterparts who got anti-HBs from natural HBV infection (infection group) for a period of five years. The positive rates of anti-HBs from the first to fifth year in the vaccine group are 97.89%, 98.95%, 81.05%, 78.95% and 72.63% respectively with one recipient remaining anti HBs negative after being immunized with three dosages of 10 micrograms plasma derived HBV vaccine in 0, 1st, 2nd month and the mean S/N values (GMV) are 30.94, 22.18, 13.61, 12.02 and 9.18 respectively. There are 26 recipients whose anti-HBs turned from positive to negative at the end of the study with a negative rate of 27.37%. The S/N GMVs in the infection group are 36.37, 27.33, 24.08 at the first, third and fifth year of the study, respectively. Both the S/N GMV and negative rate are lower than that of the vaccine group (P < 0.01). No one was found to have positive HBsAg or elevated ALT in both groups. Questions such as immune dosage, immune program and booster immunization in juvenile population are discussed. PMID- 8504701 TI - [Use of buserelin in a fertilization in vitro-embryo transfer program and determination of steroid concentrations of preovulatory follicular fluid]. AB - Eleven infertility patients, stimulated by Buserelin/hMG/hCG protocol (BHh group) for superovulation, were compared with thirteen patients using CC/hMG/hCG protocol (CHh group) in an IVF-ET program. The rates of oocyte retrieval, fertilization and cleavage in BHh group were significantly, higher than those in CHh group. Furthermore, the incidence of premature LH surge in BHh group was 0% and 23.1% in CHh group. Eventually there were four pregnancies in BHh group and only one in CHh group. The mean concentrations of estradiol (E2), progesterone (P) and P/E2 ratio in follicular fluid (FF) in BHh group were significantly lower than that in CHh group. The values of FF P/E2 ratio in the range of 10-50 were positively correlated with oocyte fertilization rates. These data suggested that the addition of Buserelin in the superovulation protocol improved the outcome of IVF-ET treatment. PMID- 8504702 TI - [Prolactin secretion in patients with endometriosis and its relationship to luteal phase defect and infertility]. AB - Serum prolactin (PRL) levels and PRL response to TRH stimulation were studied in 49 patients with endometriosis (EM) during mid-luteal phase. Eight cases with other gyn-diseases and 14 normal fertile women served as controls. Their luteal function were also estimated by three serum progesterone(P) measurements during the luteal phase and endometrial dating in the late luteal phase. RESULTS: The incidence of hyperprolactinemia in EM group (32.7%), and in EM with primary infertility group (61.5%) was significantly higher than that in normal controls (7.1%) (P < 0.05). However, the PRL secretory capacity was not positively correlated to the severity of EM. There was no difference in serum P levels between EM and two control groups. But delayed endometrial maturation was shown in 6 EM infertile cases suggesting luteal phase defect, an incidence of 27.3% (6/22) in EM group or 42.9% (6/14) in EM infertile group. Five out of the six were hyperprolactinemic and had no other identified causes of infertility. These data implied that hyperprolactinemia may impair the luteal function causing infertility in EM patients. PMID- 8504703 TI - [Transvaginal ultrasonographic monitoring on the morphological changes of ovary and endometrium during normal menstrual cycle]. AB - The morphological changes of ovary and endometrium were assessed by transvaginal ultrasonography in 35 normal menstrual cycles in the early-follicular phase, late follicular phase and luteal phase. Serum estradiol and progesterone level were determined at the same time. The mean volume of ovulatory ovary was 95.19 +/- 40.97mm3, the mean major diameter (length) was 32.44 +/- 4.29 mm and the mean minor diameter (width) was 22.92 +/- 4.23 mm just before ovulation. The difference was significant as compared with early-follicular phase (P < 0.01). There were almost no changes of volume and length of the nonovulatory ovary through the 3 phases. The number of follicles of each ovary on two sides was not different in 3 phases. The mean number of follicles of each ovary was 6.85 +/- 1.87. The mean diameter of the dominant follicle increased by 1.3 +/- 0.5 mm each day, one day before ovulation the mean diameter increased to 19.75 +/- 4.81 mm, the mean volume increased to 35.5 +/- 2.7 mm3 one day before ovulation. The thickness of endometrium increased every day in the follicular phase, and was positively correlated with E2 level. No significant changes in thickness but some changes in ultrasonic texture of endometrium in luteal phase were noticed nics. PMID- 8504704 TI - [Follicular development patterns in infertile women with biphasic basal body temperature]. AB - Seventy-one cases of infertile women with both normal menstrual cycle and biphasic BBT were studied with ultrasonography, laparoscopy, hormonal assay and endometrial histology. Signs for follicular development and ovulation were divided into four types: (1) normal ovulation in 12 cases; (2) ovulation of small follicle in 21 cases; (3) luteinized unruptured follicle in 15 cases; (4) small luteinized follicle in 23 cases. Mean serum progesterone levels in the luteal phase were within normal limits in all cases. Secretory endometrium accounted for 77.46%. Proliferative or hyperplastic endometrium accounted for 22.54%. The Authors conclude that the criteria of biphasic BBT, P levels and endometrial histology are not reliable enough for determine the cause of female infertility women. In this study the rate of salpingitis: and the rate of aberration of follicular development and chronic anovulation was 7.04%, 83.10% respectively. The latter played an important role in causing female infertility. PMID- 8504705 TI - [Maternal, medical and obstetric complications are major risk factors for low birth weight infant]. AB - The risk factors of low birth weight infant (LBW) were prospectively studied in 26,941 pregnant women. Investigations included sociodemographic risks, environmental behavioural conditions, medical diseases before pregnancy and current pregnancy complications. The adjusted odds ratios for various risk factors were calculated from multiple logistic regression model. In this analysis, placenta abnormalities uterine malformations and pregnancy-induced hypertension were shown to be the main risk factors. Preterm delivery occurred more frequently in women with diabetes and injuries in the third trimester. Term SGA babies were usually seen in women who had inadequate diet during pregnancy or in women with maternal heart disease. The risk factors of maternal age, educational background, parental smoking etc were less important than maternal diseases or pregnancy complications. The present study indicated prenatal care, started early with regular check-ups was mast important in preventing prematurity and LBW infant in China. PMID- 8504706 TI - [Mortality rate and causes of death of premature and low-birth-weight infants in 18 cities]. AB - The investigation at 19 hospitals in 18 cities showed that the incidence of premature and low-birth-weight (LBW) infant in live births was 4.9% and 5.1% respectively. The mortality rate was as high as 85.5/1000 and 97.7/1000 and the deaths accounted for 45.9% and 54.5% of total neonatal deaths respectively. The male infant's mortality rate was higher than the female; the twins' and triplets' was higher than the single births'. The mortality was mainly attributed to the preterm, LBW and related diseases. The first six causes of deaths were respiratory diseases, prenatal asphyxia, infection, scleredema congenital malformation and intracranial hemorrhage. The approaches for reducing the mortality rate of premature and LBW infants were discussed. PMID- 8504707 TI - [Pregnancy induced hypertension complicated with cerebrovascular accidents]. AB - Fourteen patients suffering from pregnancy induced hypertension (PIH) complicated with cerebrovascular accidents were admitted for treatment from 1977-1990. These were 8 cases of cerebral hemorrhage, 4 cases of cerebral infarction and 2 cases of cerebral arteriovenous malformation with intracerebral hematomas. These accounted for 0.34% of all hospitalized PIH cases during the same period and three died. The mortality rate was 0.72%. The etiology, pathology, brain CT scan features, clinical manifestations and treatment of these accidents were discussed. PMID- 8504708 TI - [Effect of serum prolactin levels on luteal function in patients with recurrent abortions]. AB - In order to evaluate the role of prolactin (PRL) on the regulation of luteal function, a series of clinical and laboratory examinations were carried out in 30 patients with history of habitual abortion. The following parameters were included: serum hormone levels by radioimmunoassay during follicular and luteal phase, ultrasonic scan of ovary and endometrial biopsy. The results indicated that: (1) The serum level of PRL was normal in 86.7% of the patients (26/30), and hyperprolactin either hypoprolactinemia accounted for 6.6% of the patients. Both hyperprolactinemia and hypoprolactinemia had abnormal development of follicles and/or luteal function deficiency (LPD) in varying degrees. (2) There were 42.3% of patients with LPD, and abnormal follicular development was one of the important causes for LPD. (3) The concentration of serum PRL showed a marked decrease in patients with spontaneous abortion (P < 0.05) as compared to that of women who went to term. It indicated that PRL level might be associated with luteal function during early pregnancy. PMID- 8504709 TI - [Human ovarian epithelial adenocarcinoma with peritoneal metastasis and ascites established in murine models]. AB - By means of SKOV3 subcutaneous xenografts in nude mice, both carcinoma cells and cell suspensions were administrated intraperitoneally to establish a model of metastatic ovarian carcinoma with ascites. The intraperitoneal metastasis and cancer cells in the ascitic fluid were all prove to be adenocarcinoma by microscopic and electromicroscopic examinations. The immunohistochemical and immunocytochemical stainings with monoclonal antibody COC166-9 were the same as SKOV3 cells. The median survival of these nude mice was 68.7 days. This may serve as a good experimental model for testing chemotherapy as well as immunotarget therapy. Similar results obtained by xenografts of OSC2. 40 nude mice were included in this study. PMID- 8504710 TI - [The present status and future prospects in clinical research on female reproductive endocrinology]. PMID- 8504711 TI - [Removal of incarcerated intrauterine devices by combined methods]. AB - Incarcerated IUDs are difficult to manage. Through clinical analysis of 41 cases with incarcerated IUDs, the value of X-ray, ultrasonographic and hysteroscopic examinations in combined use was assessed, especially in locating and describing the concrete shape of the incarcerated IUD before and during the removal operations. With the aid of these diagnostic methods 39 IUDs (95.12%) were removed through the vaginal route, while the remaining 2 (4.88%) were taken out by laparotomy, one had hyperplasia of the endometrium accompanied by retained broken pieces of the IUD, the other had uterine anomaly (uterus didelphys) with an incarcerated IUD. 40 out of the 41 IUDs were stainless steel rings, and only 1 was a Cu V IUD. The advantages and drawbacks of the three above-mentioned diagnostic were discussed as well as the effect of use. The different method of IUD removal were described. PMID- 8504712 TI - [The avoidance of early postmenopausal bone substance losses by transdermal estrogen substitution]. AB - The effect of transdermal oestrogen replacement therapy on prevention of osteoporosis was investigated in a controlled randomized study of 38 healthy women (mean age 49.6 [45-54] years) in the early postmenopausal period (< or = 3 years). 19 women (hormone group) continuously used oestrogen patches with a mean daily estradiol delivery of 0.05 mg with addition of medroxyprogesterone acetate, 5 mg orally, for 14 days per month. The other 19 women (calcium group), whose baseline levels were identical, took 500 mg calcium daily. Climacteric symptoms improved significantly in the hormone group, and serum and urinary calcium levels and total serum cholesterol all declined, while the HDL cholesterol levels increased slightly. Bone density was measured by single photon absorptiometry at two points (1/3 and 1/10 of the forearm length from the distal end of the radius). After 6 and 12 months, the values at the proximal site (1/3) had risen in the hormone group by 1.1% and 0.46% and had fallen in the calcium group by 1.96% and 2.42% respectively (both P < 0.05 vs hormone group). At the distal radial site (1/10), the values increased by 2.14% and 5.3% in the same period and fell by 3.59% and 5.67% in the calcium group. The overall difference after 12 months was 11% (P < 0.01). Transdermal oestrogen appears to be as effective as oral oestrogen replacement for prevention of osteoporosis, and should help to prevent vertebral and limb fractures in the elderly. PMID- 8504713 TI - [Abdominal actinomycosis]. AB - Twelve years after adnexectomy, performed for actinomycosis of the left ovary, a 32-year-old woman developed abdominal and back pain. A solid tumour was palpated in the left lower abdomen. Colon contrast examination revealed a subtotal stenosis in the sigmoid colon, while sonography showed a complete stenosis of the left ureter with left hydronephrosis. Relaparotomy demonstrated a stone-hard tumour at the rectosigmoid junction, which involved the right ovary and ureter, as well as having infiltrated the retroperitoneum, predominantly on the left. After resection of the sigmoid colon, uterus and right ovary, as well as of the ureteric stenosis with reanastomosis, the further course was without complication. Histological examination confirmed actinomycosis of the left ovary, sigmoid colon and pelvic mesocolon. Therapy with amoxycillin, 500 mg three times daily, was started. As the patient had worn an intrauterine pessary for several years, primary infection of the uterus with spread into the abdominal cavity via tube and ovaries is likely to have been the course of events. The recurrence was probably caused by reactivation of residual actinomycetes in the retroperitoneum and pelvic mesocolon. PMID- 8504714 TI - [The therapy of androgenetic alopecia with minoxidil]. PMID- 8504715 TI - [The immune defect in kidney failure. II. The mechanisms of the "uremic" immune defect]. PMID- 8504716 TI - [Post hoc or propter hoc? On the heuristics of side-effects in the example of gynecomastia]. PMID- 8504717 TI - [Osteomyelofibrosis as a prognostic factor in myeloproliferative diseases?]. PMID- 8504718 TI - [Cracking noises in the ear]. PMID- 8504719 TI - [Migraine treatment in children]. PMID- 8504720 TI - [Overweight youth]. PMID- 8504721 TI - [The treatment of chronic hepatitis B]. PMID- 8504722 TI - [Histopathological changes of gallbladder and liver parenchyma in symptomatic cholelithiasis]. AB - In a retrospective study of 1101 patients (302 men, 799 women; mean age 56,7 [19 88] years) with symptomatic cholelithiasis who had undergone elective cholecystectomy and intraoperative liver biopsy, histological examination revealed inflammatory changes in the gallbladder in 96.7%, chronic fibrotic cholecystitis in 94.5% and a severe form of cholecystitis in 8.8%. Clinically relevant changes in the liver parenchyma were present in 27.9%, most frequently intrahepatic cholangitis (21.8%). The latter was significantly more common in choledocholithiasis than in isolated cholecystolithiasis. 27 patients had signs of severe liver disease, namely viral hepatitis, cirrhosis or fatty liver. Since the gall-bladder in cholelithiasis is almost always inflamed, cholecystectomy is the treatment of choice. Not uncommonly liver biopsy will reveal clinically relevant changes in the liver parenchyma. This will be useful information, especially in the management of symptoms which persist postoperatively. PMID- 8504723 TI - [Suprasellar space-occupying lesion as initial manifestation of tuberculosis in childhood]. AB - Three days after having sustained a mild trauma to the head a seven-year-old boy developed seizure-like rotatory vertigo. Computed tomography, magnetic resonance imaging and cerebral angiography demonstrated a suprasellar space-occupying lesion. Pulmonary tuberculosis was discovered in subsequent diagnostic work-up. Cerebrospinal fluid examination was unremarkable except for immunological tests (tuberculostearic acid) which pointed to central nervous system (CNS) involvement so that a tuberculoma was suspected. The lesion decreased in size on tuberculostatic treatment (200 mg/d isoniazid, 200 mg/d rifampicin, two times 250 mg/d pyrazinamide). In the next 12 months there merely persisted a mild abnormality of the blood-brain barrier with a little contrast-medium uptake, which regressed in the following 6 months. The differential diagnosis between CNS tuberculosis and brain tumour or pyogenic abscess can be difficult in children if there are no pulmonary signs and/or the cerebrospinal fluid is normal. PMID- 8504724 TI - [Diagnosis of pelvic floor insufficiency]. PMID- 8504725 TI - [Advances in the prevention and therapy of common chemotherapy-induced side effects]. PMID- 8504726 TI - [Good clinical practice. Reorientation in clinical research. European Society for Good Clincial Practice]. PMID- 8504727 TI - [Venous thrombosis of the lower leg]. PMID- 8504729 TI - [Cholesterol--a marker for multiple risk factors]. PMID- 8504728 TI - [TUR syndrome in transurethral prostate resection]. PMID- 8504730 TI - Surprising places of estrogenic activity. PMID- 8504731 TI - Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. AB - In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast-conditioned media showed the presence of a substance that competed with [3H]estradiol for binding to estrogen receptors (ER) from rat uterus. However, it soon became clear that the estrogenic substance in the conditioned media was not a product of the yeast grown in culture, but was leached out of the polycarbonate flasks during the autoclaving procedure. [3H]Estradiol displacement activity was monitored by ER RRA, and the active substance was purified from autoclaved medium using a series of HPLC steps. The final purified product was identified as bisphenol-A (BPA) by nuclear magnetic resonance spectroscopy and mass spectrometry. BPA could also be identified in distilled water autoclaved in polycarbonate flasks without the requirement of either the organism or the constituents of the culture medium. Authentic BPA was active in competitive RRAs, demonstrating an affinity approximately 1:2000 that of estradiol for ER. In functional assays, BPA (10-25 nM) induced progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of approximately 1:5000 compared to that of estradiol. The BPA effect on PR induction was blocked by tamoxifen. In addition, BPA (25 nM) increased the rate of proliferation of MCF-7 cells assessed by [3H]thymidine incorporation. Thus, BPA exhibited estrogenic activity by both RRA and two functional bioresponse assays. Finally, MCF-7 cells grown in media prepared with water autoclaved in polycarbonate exhibited higher progesterone receptor levels than cells.grown in media prepared with water autoclaved in glass, suggesting an estrogenic effect of the water autoclaved in polycarbonate. Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment. PMID- 8504732 TI - Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) is responsible for the interconversion of cortisol to cortisone [corticosterone (B) to 11 dehydrocorticosterone in rodents] and confers ligand specificity to the mineralocorticoid receptor. Inhibition of 11 beta HSD by licorice derivatives [glycyrrhizic and glycyrrhetinic (GE) acids] results in cortisol/B and not aldosterone acting as a potent mineralocorticoid. 11 beta HSD is ubiquitously expressed and, by converting active glucocorticoid to inactive metabolites, may be an important prereceptor regulator of ligand access to the glucocorticoid receptor (GR). To investigate this further, we have studied the effect of 11 beta HSD inhibition by licorice derivatives on PRL gene expression (a known glucocorticoid target gene) in rat pituitary GH3 cells. Glycyrrhizic acid administration to rats in vivo (75 mg/kg.day for 5 days) resulted in inhibition of 11 beta HSD activity, as previously reported, but also a significant reduction in steady state 11 beta HSD mRNA levels in both predominantly mineralocorticoid (kidney and distal colon) and glucocorticoid (liver and pituitary) target tissues. In vitro, 11 beta HSD mRNA and activity were present in rat pituitary GH3 cells (81% conversion of B to 11-dehydrocorticosterone/4 x 10(6) cells after 24-h incubation) and inhibited by GE in a dose-dependent fashion. While B or GE alone (10(-8)-10(-5) M) had little or no effect on PRL mRNA levels or immunoassayable PRL, combinations of GE plus B resulted in marked inhibition of PRL mRNA levels and secretion, to such an extent that a concentration of 10(-6) M B with 10(-6) M GE was more potent than equimolar concentration of the synthetic GR agonist RU 28362. This inhibitory effect on PRL mRNA levels was blocked by a 10-fold excess of the GR antagonist RU 38486, but not by a 10-fold excess of the mineralocorticoid receptor antagonist RU 26752, confirming that this potentiation of glucocorticoid hormone action was operating through the GR and not the mineralocorticoid receptor. In addition to its established role as a competitive inhibitor of 11 beta HSD, licorice results in pretranslational inhibition of 11 beta HSD both in vitro and in vivo. 11 beta HSD is clearly an important mechanism in regulating tissue levels of active glucocorticoid and, hence, ligand supply to the GR. PMID- 8504733 TI - Inhibition of insulin-degrading enzyme increases translocation of insulin to the nucleus in H35 rat hepatoma cells: evidence of a cytosolic pathway. AB - We previously demonstrated the translocation of insulin to the nucleus in several cell types and partially characterized the uptake mechanisms and pathways in H35 rat hepatoma cells. Nuclear accumulation of insulin was energy independent, time and temperature dependent, and apparently was not saturable at insulin concentrations which resulted in full receptor occupancy. We also have shown insulin could be internalized by both receptor-mediated and fluid-phase endocytosis. This study investigated subsequent steps involved in the nuclear accumulation of insulin following internalization. We examined the effects of inhibiting insulin degrading enzyme (IDE) with 1,10-phenanthroline on the nuclear accumulation of insulin in H35 cells. 1,10-phenanthroline (2 mM) which markedly inhibited insulin degradation, significantly increased nuclear accumulation of insulin without having any effects on total cell-associated and intracellular insulin. This reagent increased 125I-insulin on the cellular membrane and decreased 125iodine (125I-insulin and 125I-insulin degradation products) in the cytosolic fractions. Chemical extraction and Sephadex G-50 chromatography revealed the insulin associated with the nucleus in 1,10-phenanthroline-treated cells formed the same complex(es) with the nuclear matrix as in control cells. These results suggested that inhibition of cytosolic IDE activity resulted in increased insulin translocation from the cytosol to the nucleus. Furthermore, when IDE activity was inhibited by high cytosolic insulin concentrations, the amount of 125I-insulin in the nucleus was significantly increased. Our study suggests internalized insulin is probably released from endosomes into the cytosol where modulation of IDE activity could have significant effects on the accumulation of insulin, or insulin-cytoplasmic protein complexes, in nuclei. The IDE regulatory mechanism, by controlling the translocation of insulin to the cell nucleus, could play a crucial role in insulin's regulation of gene expression and cell proliferation. PMID- 8504734 TI - Sexual differentiation of vasopressin projections of the bed nucleus of the stria terminals and medial amygdaloid nucleus in rats. AB - The vasopressin-immunoreactive (AVP-ir) projections of the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA) are much denser in males than in females even if males and females are treated with similar amounts of testosterone. Previous studies have established that testosterone influences AVP-ir projections during development, but not whether these effects of testosterone were permanent. This study tested the effects of various hormonal manipulations during development on the ability of testosterone to influence the AVP immunostaining in cells of the BST and MA and of fibers in the lateral septum of adult rats. In the first experiment, male rats that were castrated at 3 months of age (control males) had more AVP-ir cells in the BST and a higher density of AVP-ir fibers in the lateral septum than neonatally castrated male rats, whose cell numbers and fiber density did not differ from female rats that were ovariectomized neonatally or at 3 months of age (control females). This suggested that testicular secretions influence sexual differentiation of AVP-ir fiber pathways after birth. The second experiment showed that males castrated at the day of birth or at 1 week after birth had less AVP-ir cells in the BST and MA and a lower AVP-ir fiber density in the lateral septum than male rats castrated at the third week after birth or control males. This indicated that testicular secretions influenced the differentiation of AVP-ir pathways around postnatal day 7. This was further confirmed in the third experiment, in which testosterone propionate treatment at the seventh postnatal day significantly raised AVP-ir fiber density in the lateral septum of neonatally gonadectomized male and female rats and fully restored the number of AVP-ir cells in the BST of neonatally castrated males. Combined, these data suggest that testosterone levels around the seventh postnatal day determine the sexual differentiation of AVP-ir projections to the lateral septum. PMID- 8504735 TI - Perifusion of rat pituitary cells with gonadotropin-releasing hormone, activin, and inhibin reveals distinct effects on gonadotropin gene expression and secretion. AB - Gonadotropin biosynthesis and secretion are influenced by pulsatile GnRH derived from the hypothalamus as well as by paracrine factors. In the current studies, we compared the effects of inhibin, activin, and GnRH, alone and in combination, on gonadotropin subunit messenger RNA (mRNA) levels and gonadotropin secretion. A pituitary perifusion system was used to allow GnRH to be administered as pulses and to minimize paracrine effects. FSH beta mRNA levels were increased 25-fold by a maximal concentration of activin (3 ng/ml) and suppressed 83% by a maximal concentration of inhibin (30 ng/ml). When activin and inhibin were perifused together, inhibin attenuated the effects of maximal activin stimulation in a concentration-dependent manner, with a 10-fold excess of inhibin required to block the effects of activin entirely. Whole cell receptor assays using 125I labeled activin confirmed that the inhibin used in the perifusion experiments competed for activin binding sites, although with a lower affinity. Direct competition at the activin receptor may thus account for part of the activin/inhibin antagonism observed at the level of FSH beta mRNA. Neither activin nor inhibin had a significant effect on levels of LH beta or alpha mRNAs. Hourly pulses of 10 nM GnRH elicited a 2- to 5-fold increase in FSH beta mRNA. This increment was maintained in the presence of activin and inhibin, suggesting separate, but dependent, mechanisms of action for GnRH vs. inhibin and activin. In studies of secretion, continuous activin stimulation (3 ng/ml) elicited only a small (approximately 30%) increase in basal FSH secretion. However, the response of FSH to pulses of GnRH was amplified 3-fold in the presence of activin. A similar enhancement of GnRH-induced, but not basal, LH release was also observed. Inhibin, in contrast, elicited no changes in basal or GnRH-stimulated release of FSH or LH. We conclude that activin and inhibin are the primary regulators of FSH beta mRNA levels, whereas GnRH appears to be the major effector for gonadotropin secretion. There is significant functional overlap, however, and the combined actions of activin, inhibin, and GnRH determine the final level of FSH beta mRNA and the pattern of gonadotropin secretion. PMID- 8504736 TI - Glucose regulates glut 1 function and expression in fetal rat lung and muscle in vitro. AB - The mechanisms that regulate cellular glucose transport (glucose uptake, Glut 1 protein, and mRNA) in the fetus are not known. We attempted to define the effects of glucose availability alone in vitro on glucose transport in fetal rat lung and muscle. On day 20 of gestation (term = 21.5 days), lung and muscle tissues were harvested from normal fetal rats, minced into explants, and cultured for 24 h in standard culture medium (lung, 28 mM; muscle, 5.5 mM glucose). Explant cultures were washed and cultured for an additional 1 or 24 h in medium containing one of four concentrations of glucose: 1) glucose free, 2) low glucose, 3) high glucose, and 4) standard. Twenty-four-hour, but not 1-h, treatment of fetal lung and muscle in vitro with low concentrations of glucose increased 2-deoxyglucose uptake and Glut 1 protein and mRNA levels (P < 0.05). Culture in high glucose medium for 24 h, but not 1 h, decreased 2-deoxyglucose uptake and Glut 1 protein and mRNA levels (P < 0.05). Culture in glucose-free medium for 24 h up-regulated glucose transport in lung and down-regulated glucose transport in muscle, indicating that regulation of fetal glucose transport may be tissue specific. These findings differ from our studies of in vivo models of altered fetal growth and abnormal glucose availability. Maternal bilateral uterine artery ligation limits glucose availability to the fetus, and glucose transport is down regulated. Low glucose in vitro has the opposite effect. Maternal diabetes increases glucose availability to the fetus, and glucose transport is up regulated. High glucose in vitro does the opposite. We conclude that while glucose alone in vitro affects its uptake by the cell, other factors that are altered in these in vivo conditions act in concert with glucose to regulate glucose transport in the fetus. PMID- 8504737 TI - Thyroxine increases the levels of epidermal growth factor messenger ribonucleic acid (EGF mRNA) in the thyroid in vivo, as revealed by quantitative reverse transcription polymerase chain reaction with an internal control EGF mRNA. AB - Treating mice with T4 increases the level of immunoreactive epidermal growth factor (EGF) in the thyroid. In order to establish whether this response might reflect a T4-dependent increase in the levels of messenger RNA (mRNA) in the thyroid, we prepared an internal standard which permits us to quantitate EGF mRNA levels by reverse transcription plus polymerase chain reaction amplification (RT PCR). Our synthetic EGF mRNA construct contains the same flanking primer sequences used to amplify mature EGF message, but 70 bases were eliminated from the center of the 277-base EGF sequence to permit the PCR product of this internal standard to be distinguished by its smaller size (EGF 207). This synthetic mRNA also contains a poly(A)tail, which permits it to be reverse transcribed. We then added a range of concentrations of this internal standard mRNA to aliquots of total RNA from each pair of thyroid lobes and determined the concentration of EGF 207 at which the PCR primers were incorporated equally into the 277 and 207 bands after RT-PCR. Thyroid RNA from male Balb/c mice treated with T4 (0.25 micrograms/g.day) for 14 days contained 2.8-fold more EGF mRNA than RNA from control mice (P < 0.01). Competitive RT-PCR EGF mRNA levels were determined for thyroid RNA samples from mice treated with T4 for various times up to 14 days. The most significant increase occurred after 1 day's treatment (P < 0.005). This demonstration of a thyroid hormone-dependent increase in the level of thyroidal EGF mRNA adds support to the concept that EGF may function as an autocrine/paracrine regulator of thyroid function. PMID- 8504738 TI - Opposite, phase-dependent effects of 3,4,5-trimethoxybenzoic acid 8 (diethylamino) octyl ester or tetracaine on islet function during three phases of glucose-stimulated insulin secretion. AB - The spontaneous decline of insulin secretion which occurs under a variety of secretory conditions is well documented and suggests a general desensitization of the secretory process distal to signal recognition. Accordingly, we have investigated the effects of agents thought to mobilize intracellular Ca++ on insulin secretion over 24 h, which includes periods of rising secretory activity (second phase) and desensitized secretory activity (third phase). During the first 3 h of glucose stimulation of freshly isolated rat islets, insulin secretion was strongly inhibited by 30 microM 3,4,5-trimethoxybenzoic acid 8 (diethylamino) octyl ester (TMB) or 300 microM tetracaine hydrochloride (TC). However, when either of these agents was added for the first time to islets at h 20 when insulin secretion was at a low steady rate (third phase), insulin secretion was greatly enhanced. Both these inhibitory and stimulatory effects declined with continued administration. Removal of TMB and rechallenge with high glucose plus forskolin uncovered a residual inhibition in both chronically and acutely treated islets. Coadministration of forskolin with either TMB or TC blunted both inhibitory and stimulatory effects. Pertussis toxin pretreatment, however, did not alter subsequent response of islets to either agent. Thus TMB or TC have opposite, phase-dependent effects on glucose-stimulated insulin secretion. We postulate that potentiators of glucose-stimulated insulin secretion, which are increased during second phase, are most sensitive to inhibitory effects of TMB or TC, and that the low steady rate of third phase permits their stimulatory component(s) to become apparent. PMID- 8504739 TI - Recombinant human inhibin A and recombinant human activin A regulate pituitary and ovarian function in the adult female rat. AB - The roles of recombinant human inhibin A (rh-inhibin A) and rh-activin A in regulating the pituitary and ovary of the adult female rat were examined. Serum and pituitary FSH and LH and serum estradiol and progesterone concentrations were evaluated at 1, 2, and 6-12 h after sc hormone administration on metestrus and on proestrus. A second study examined the effect of the hormones 24 h after injection at 1000 h on each day of the cycle. Rh-inhibin A inhibited FSH secretion 60 min after injection on proestrus but did not alter serum FSH concentration on metestrus. FSH remained low for the 12 h examined during the evening of proestrus and on the morning of estrus. Serum LH concentration, pituitary FSH content, and pituitary LH content were not significantly changed under any experimental condition. Rh-inhibin A did not regulate estradiol concentration on metestrus or on proestrus; however, it did cause a rise in serum estradiol in animals treated on metestrus and diestrus and examined 24 h later. This suggests that inhibin may participate in regulating follicular maturation in a subset of developing follicles. Last, after rh-inhibin A treatment, the duration of the proestrus progesterone surge was shortened. Serum FSH concentration rose by 6 h after rh-activin A administration on proestrus and both FSH and LH rose by 6 h after hormone administration on metestrus. Rh-activin A significantly increased serum estradiol through 6 h of treatment on proestrus. Progesterone levels were significantly greater in animals treated on metestrus and killed 24 h later. The increased length of the midcycle progesterone surge may be the result of increased LH on metestrus. These studies suggest that rh inhibin A and rh-activin A may regulate ovarian and pituitary function in a cycle dependent manner. Specifically, rh-inhibin A can acutely regulate FSH and progesterone on proestrus and estradiol during follicular development. Rh-activin A acutely regulates FSH on both proestrus and metestrus and LH on metestrus. Whether circulating endogenous inhibin or activin participate physiologically in these functions is under investigation. PMID- 8504740 TI - Localization and measurement of corticostatin-I in nonpregnant and pregnant rabbit tissues during late gestation. AB - Corticostatin-I (CSI) is the most potent of the corticostatic peptides isolated from rabbit lungs and neutrophils. CSI was localized in cells by immunohistochemistry using highly specific polyclonal antisera raised against the synthetic peptide. Western blot showed a single 4-kilodalton band, indicating that the antibody employed was specific for CSI in spleen, intestine, adrenal, and lung, but no CSI band was observed in liver. CSI was localized to macrophages in spleen, adult lung, placenta, and adult duodenum. CSI was found in epithelial cells of the upper half of the villi of the small intestine, but not in the Paneth cells. In the adrenal, CSI staining was observed only in the zona fasciculata and zona reticularis, and no immunostaining was observed in kidney, liver, heart, or ovary. CSI was measured in the maternal and fetal tissues of the pregnant rabbit on days 24, 27, and 30 of gestation and in nonpregnancy tissues. First, the peptide was extracted using mild acid conditions, purified by HPLC, and then quantitated by RIA. Immunoreactive CSI was highest in lung, spleen, intestine, and adrenal. In the brain, CSI was found in higher amounts in the pituitary, hypothalamus, and thalamus, with peak values observed at 27 days gestation. The largest amounts were found in the pituitary and hypothalamus of the nonpregnant animal. Rabbit lung had large amounts of immunoreactive CSI, with rising values in both maternal and fetal lung with progressing gestation. Again, the highest amounts were found in the lung of the nonpregnant rabbit. The adrenal contained large amounts of immunoreactive CSI, and the fetal adrenal concentrations declined with progressing pregnancy, whereas the maternal adrenal values were much lower and showed a small decline at 27 and 30 days gestation. The placenta had large amounts of immunoreactive CSI, which increased with progressing gestation. In fetal and maternal plasma, there were small amounts of ACTH, which remained constant in the maternal circulation, but increased in the fetal circulation with progressing gestation. Immunoreactive CSI was present in plasma in a much higher concentration, which decreased in the fetal compartment but increased in the maternal compartment with progressing gestation. The data presented indicate that CSI is localized to a large number of tissues in the rabbit, as visualized by immunoperoxidase staining, and that in a number of tissues it is found in macrophages. After HPLC purification from tissues, CSI was measured by RIA and found in all tissues examined except liver, kidney, heart, and ovary.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504741 TI - Regulation of gonadotropin-releasing hormone by protein kinase-A and -C in immortalized hypothalamic neurons. AB - As major signal transduction cascades, the protein kinase-A and -C (PKA and PKC) pathways have been implicated in the regulation of GnRH synthesis and secretion in the hypothalamus. We have investigated the roles of these pathways in the regulation of GnRH transcription, mRNA levels, propeptide processing, and secretion in GT1-7 cells, a mouse hypothalamic GnRH neuronal cell line. Forskolin, which activates adenylate cyclase to raise cAMP levels, had no effect on GnRH mRNA levels at 10 microM, but induced c-fos mRNA at 30 min. An activator of PKC, 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM), also induced c-fos at 30 min, but produced a progressive decline in GnRH mRNA, resulting in a 70% decrease by 16 h. Coadministration of 10 nM TPA and 20 microM of a PKC inhibitor, NPC 15437 [2,6-diamino-N-([1-(1-oxotridecyl)2-piperidinyl]methyl)hexanami de], prevented c-fos induction, but did not antagonize GnRH repression. Instead, the inhibitor itself reduced GnRH mRNA levels by 56% at 16 h (with no effect on c-fos mRNA). Thus, since extended exposure to TPA can down-regulate PKC, suppression of GnRH mRNA by TPA may be due to decreased PKC activity, indicating a role for PKC in the maintenance of the GnRH gene expression (a role that is unlikely to involve c-fos). In transient transfections, the transcriptional activity from 3 kilobases of GnRH 5'-flanking sequence was repressed 2-fold by either 100 nM TPA or 20 microM NPC 15437 at 24 h, demonstrating that suppression of GnRH mRNA is at least, in part, at the level of transcription. In contrast, both TPA (100 nM) and forskolin (10 microM) stimulated secretion. Enhancement of GnRH secretion by TPA was robust and rapid (2.5 min), while the response to forskolin was relatively delayed (2 h). Over a 24-h period, unstimulated cells released primarily unprocessed prohormone, whereas forskolin and TPA stimulated the secretion of processed products. These data indicate that PKC and PKA may influence propeptide processing and/or the route of GnRH secretion. These data demonstrate that the PKA and PKC pathways regulate GnRH at the multiple levels of transcription, pro GnRH processing, and GnRH secretion. PMID- 8504742 TI - Regulation of progesterone receptor gene expression and growth in the rat uterus: modulation of estrogen actions by progesterone and sex steroid hormone antagonists. AB - Although the rat uterus has often been used as a model to study estrogen action, relatively little is known of the mechanism(s) by which estrogen regulates uterine progesterone receptor (PR) levels in this species. In the present study, we used immature ovariectomized rats to examine the regulation of PR gene expression and growth in the uterus by estradiol (E2) as well as hormonal modulators of E2 action, namely progesterone (P), the antiestrogen LY117018 (LY), and the antiprogestin RU486. Northern blot analyses revealed eight PR mRNA species ranging in size from 3.3-14 kilobases, with the most abundant being 7.1 kilobases. E2 treatment caused rapid time- and dose-dependent increases in the steady state levels of PR mRNA, which peaked at 24 h (6-fold increase) and declined thereafter. All eight PR mRNA transcripts increased proportionally in response to E2. Immunoblot analyses indicated that these changes were accompanied by increases in PR protein (6-fold increase by 48 h), which continued to accumulate over time, unlike PR mRNA, which decreased despite continued E2 exposure. In contrast to the stimulatory effect of E2 on PR, the levels of immunoreactive estrogen receptor were reduced to about 15% of the control value by E2 within 48 h and remained low throughout the remaining treatment period. Treatment with P blocked the stimulatory effects of E2 on both PR mRNA and protein. These antagonistic actions of P were prevented by simultaneous administration of RU486. LY, which caused a slight (approximately 2.5-fold) increase in PR mRNA when administered alone, was an effective antagonist of E2 stimulated increases in PR mRNA. However, LY was incapable of completely antagonizing E2-stimulated increases in PR protein. The differences between the profiles of the time-dependent increases in PR mRNA and protein in response to E2, as well as the different sensitivities of these two end points to the antagonistic actions of LY, highlight the lack of direct correspondence between these two end points and suggest that E2 may be acting through distinct mechanisms (transcriptional and posttranscriptional, for example) to increase the levels of PR in the rat uterus. Our results indicate that E2 rapidly increases uterine PR expression and growth, and that P as well as sex steroid hormone antagonists are important modulators of these E2 actions in the rat uterus. PMID- 8504743 TI - Effects of neonatal estrogen exposure on prostatic secretory genes and their correlation with androgen receptor expression in the separate prostate lobes of the adult rat. AB - Brief administration of estrogen to newborn rats permanently restricts prostatic growth and testosterone sensitivity in adulthood. Previous work demonstrated that neonatal exposure to estradiol benzoate produced lobe-specific imprints in prostatic androgen receptor (AR) expression. Epithelial cell AR was markedly reduced or absent in the adult ventral and dorsal lobes, which correlated with a lack of epithelial differentiation and responsiveness. While the lateral lobe also showed reduced growth and testosterone responsiveness after neonatal estradiol benzoate, normal cell differentiation and AR levels were observed within the adult epithelium. To determine the impact that these receptor imprints have on the functional capacity of adult tissue, we herein examined the expression of lobe-specific, androgen-dependent, or androgen-responsive secretory genes in prostates of rats given neonatal estradiol benzoate and directly compared this with epithelial cell AR using histological techniques. Sprague Dawley rat pups were given 25 micrograms estradiol benzoate or oil on days 1, 3, and 5 and killed on day 90. Prostatic mRNA was analyzed using Northern blots and in situ hybridization. Ventral lobe mRNA was hybridized with a prostate binding protein (PBP) cDNA probe, while lateral and dorsal mRNA were hybridized with RWB (seminal vesicle secretory protein or SVS-II), probasin, and DP1 cDNA probes. Sections adjacent to those used for in situ hybridization were stained for AR by immunocytochemistry. Neonatal estradiol benzoate significantly reduced ventral lobe PBP message on Northern blots, and this was not restored with adult testosterone administration. There was a direct correlation between epithelial cell AR and PBP expression, in that PBP message and protein were only present in epithelial AR-positive cells and were absent in all AR-negative epithelium. In the lateral prostate, probasin expression was unaffected by neonatal estradiol benzoate, whereas RWB was slightly reduced using Northern analysis. By in situ hybridization, these messages were observed at normal levels in lateral lobe epithelial cells of estrogenized rats, which directly correlated with the presence of AR in those cells. In the dorsal prostate, different response patterns to neonatal estradiol benzoate were found for the three secretory genes analyzed. On Northern blots, DP1 message significantly declined, probasin mRNA was modestly suppressed, and RWB expression was significantly elevated compared to those in control tissue. In situ hybridization revealed that RWB expression in estrogenized dorsal lobes was amplified in AR-positive epithelial cells, whereas AR-negative cells appeared unaltered. In summary, prostatic functional activity after neonatal estradiol benzoate exposure is affected in a lobe-specific manner, which correlates with the AR imprints in the separate lobes. PMID- 8504744 TI - Comparison of the effects of pulsatile and constant testosterone on the secretion of gonadotropins in the ram. AB - The objective of the present study was to compare the effectiveness of a pulsatile vs. a constant pattern of testosterone (T) infusion to suppress LH and FSH secretion in wethers. Two separate experiments were conducted. In Exp 1, animals were subjected to each of four different iv infusion regimens for 3 days: 1) constant diluent, 2) constant T (768 micrograms/kg.24 h), 3) pulsatile (one pulse every 4 h) diluent, and 4) pulsatile T (768 micrograms/kg.24 h). Blood samples were collected at 10-min intervals for 4 h both before infusion and during the last 4 h of the infusion. Compared to diluent, T decreased (P < 0.001) mean LH and increased (P < 0.001) LH interpulse interval. The LH interpulse interval was increased more (P < 0.005) by constant T than by pulsatile T. Mean LH was slightly more suppressed (P = 0.052) by constant T than by pulsatile T. LH pulse amplitude did not differ between constant T and pulsatile T. In Exp 2, animals were subjected to each of three different iv infusion regimens for 4 days: 1) constant diluent, 2) constant T (384 micrograms/kg.24 h), and 3) pulsatile (one pulse every 6 h) T (384 micrograms/kg.24 h). Both LH the interpulse interval (P = 0.001) and LH pulse amplitude (P = 0.04) were increased more by constant T than by pulsatile T. Mean LH was suppressed more (P = 0.002) by constant T than by pulsatile T. In both Exp 1 and 2, none of the treatments significantly affected mean FSH. These results indicate that constant T is more effective than pulsatile T in suppressing LH secretion in the ram. PMID- 8504745 TI - Prolactin mediates estradiol-induced inflammation in the lateral prostate of Wistar rats. AB - Inflammation was induced in the lateral prostate of castrated Wistar rats by exposure to a sc implant of estradiol-filled Silastic tubing, followed by the addition of a dihydrotestosterone implant to restore prostatic wet weight. The presence of inflammation was correlated with increased serum PRL, elevated pituitary weight, and a greater than 2-fold increase in the lateral prostate DNA concentration. The administration of bromocriptine (4 mg/kg.day) to these animals was effective in suppressing pituitary weight and hyperprolactinemia and mitigated the lateral prostate inflammatory response. Inflammation was restored in the bromocriptine-treated hormone-implanted rats by administering exogenous ovine PRL at a dose of 2 mg/kg twice a day. The results indicate that estradiol induced inflammation in the rat lateral prostate is mediated at least in part by the release of PRL from the pituitary. PMID- 8504746 TI - Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. AB - Administration of the goitrogen, 6-propyl-2-thiouracil (PTU), to suckling rat pups from birth through day 24 postpartum as a 0.1% solution in the mother's drinking water increases adult testis size and sperm production by about 80% and 140%, respectively, without affecting peripheral testosterone levels. The objectives of this study were to determine whether adult Leydig cell numbers were altered in PTU-treated rats and whether the steroidogenic function of these cells was normal. The number of Leydig cells per testis at 180 days increased by 69% in PTU-treated compared to control rats, whereas the average Leydig cell volume declined by about 20%. Steroidogenic function assessed in isolated adult Leydig cells decreased after neonatal PTU treatment. LH-stimulated testosterone production was reduced by 55% in Leydig cells from treated rats, commensurate with a 50% decline in the number of hCG-binding sites in these cells. The difference in steroidogenic potential was even more striking after incubations with saturating concentrations of steroid substrate, 22(R)-hydroxycholesterol; Leydig cells from treated males produced 73% less testosterone than controls. Therefore, this decrease in testosterone production may be partially due to a reduction in the numbers of LH receptors, but also reflects the impaired steroidogenic potential of these cells. These results clearly show that the dramatic increase in adult Leydig cell number after neonatal PTU treatment is counterbalanced by a permanent decline in Leydig cell steroidogenic function, producing no net change in peripheral testosterone levels. PMID- 8504747 TI - Aldosterone stimulated differentiation of mouse 3T3-L1 cells into adipocytes. AB - We find that 1-10 nM aldosterone can induce differentiation of 3T3-L1 cells into adipose cells as evaluated by microscopic accumulation of fat droplets and quantitative measurement of triglycerides and of glycerol-3-phosphate dehydrogenase, an enzyme specific for adipocyte differentiation. Moreover, the aldosterone antagonist ZK91587 inhibits aldosterone-but not glucocorticoid mediated differentiation of 3T3-L1 cells. Steroid binding assays with 3T3-L1 cells indicate the presence of specific binding sites for aldosterone. We conclude that there is an aldosterone receptor-mediated pathway for terminal differentiation of 3T3-L1 cells into adipose cells. Receptors for aldosterone have also been found in a variety of cells that do not function to regulate sodium and potassium transport. The aldosterone receptor may have a role in regulation expression of genes involved in differentiation of these cells. PMID- 8504748 TI - The role of tumor necrosis factor-alpha in the regulation of mouse Leydig cell steroidogenesis. AB - Tumor necrosis factor-alpha (TNF alpha), a cytokine secreted by activated macrophages, has been shown to modulate Leydig cell steroidogenesis. The present study examined the regulation of mouse Leydig cell function by TNF alpha at the molecular level. The effects of TNF alpha on both basal and 8-Br-cAMP-stimulated testosterone production, as well as cholesterol side-chain cleavage enzyme (P450scc) and 17 alpha-hydroxylase/C17,20 lyase (P450c17), were investigated. Treatment of Leydig cells with 0.1, 1.0, and 10.0 ng/ml TNF alpha inhibited basal testosterone secretion by 20 +/- 5.0%, 61.1 +/- 6.6%, and 60.7 +/- 5.8% of control, respectively, but had no effects on basal P450scc messenger RNA (mRNA) or protein levels. Treatment of Leydig cells with 8-Br-cAMP caused a 150.7 +/- 32.9-fold increase in testosterone production and marked stimulation of P450scc and P450c17 mRNA and protein accumulation. TNF alpha caused a significant and dose-dependent inhibition of 8-Br-cAMP-stimulated testosterone secretion by 35.9 +/- 9.9%, 90.9 +/- 1.7%, and 96.9 +/- 1.4% with 0.1, 1.0, and 10.0 ng/ml TNF alpha, respectively. TNF alpha also caused a decrease in P450scc and P450c17 mRNA and protein. Treatment with 0.1, 1.0, and 10.0 ng/ml TNF alpha decreased 8-Br cAMP-stimulated P450scc mRNA by 11.5 +/- 6.9%, 29.3 +/- 2.7%, and 59.2 +/- 8.7%, and decreased 8-Br-cAMP-induced P450c17 mRNA 41.9 +/- 13.5%, 95.7 +/- 2.3%, and 98.5 +/- 1.2%, respectively. The inhibitory effects of TNF alpha on 8-Br-cAMP stimulated P450 enzyme protein accumulation were also dose dependent, 35.6 +/- 11.4%, 52.9 +/- 14.1%, and 56.0 +/- 7.9% inhibition of P450scc protein levels, and 65.8 +/- 9.4%, 95.5 +/- 1.9%, and 96.9 +/- 2.1% suppression on P450c17 protein levels were observed with 0.1, 1.0, and 10.0 ng/ml TNF alpha, respectively. The inhibitory effect of TNF alpha on 8-Br-cAMP-induced P450c17 mRNA expression was reversible. Within 48 h after the removal of TNF alpha from culture, P450c17 mRNA was restored to 80.6 +/- 3.1% of the level in cultures treated with 8-Br-cAMP alone for 4 days. TNF alpha-mediated inhibition of 8-Br cAMP-stimulated testosterone secretion from Leydig cells was also reversible. In addition, no significant cell mortality was noted in TNF alpha-treated cells. These data demonstrate that TNF alpha inhibits both basal and 8-Br-cAMP stimulated testosterone secretion from Leydig cells in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504749 TI - Mechanism of fatty acid inhibition of aldosterone synthesis by bovine adrenal glomerulosa cells. AB - Previous work from this laboratory has suggested that the adrenal glomerulosa is under tonic inhibition by fatty acids. The purpose of the present work was to define the mechanism by which fatty acids inhibit aldosterone synthesis. Experiments with isolated bovine adrenocortical cells showed the following. 1) Fatty acids inhibited angiotensin-II-stimulated and (Bu)2cAMP-stimulated aldosterone synthesis with similar potencies. 2) Inhibition of aldosterone synthesis was highly dependent on fatty acid chain length and degree of unsaturation as well as on configuration of double bonds. Oleic acid was the most potent inhibitor among fatty acids prominent in plasma. 3) Cortisol synthesis was less sensitive to oleic acid inhibition than was aldosterone synthesis. 4) Pregnenolone synthesis by angiotensin-II-stimulated adrenal glomerulosa cells was relatively insensitive to oleic acid. 5) For both glomerulosa and fasciculata cells, cortisol synthesis from 21-deoxycortisol, which requires the participation of P450(21), was relatively insensitive to fatty acids. Cortisol synthesis from corticosterone by fasciculata cells, which requires the participation of P450(17) alpha, was also insensitive to oleic acid. These are microsomal enzymes. 6) In glomerulosa cells, aldosterone synthesis from added corticosterone, which requires the 18-oxidase function of P450(11) beta, a mitochondrial enzyme, was potently inhibited by fatty acids; cortisol synthesis from 11-deoxycortisol by glomerulosa cells, which requires P450(11) beta, was less sensitive to inhibition, and cortisol synthesis from 11-deoxycortisol by fasciculata cells was even less sensitive. 7) Aldosterone synthesis from exogenous 18 hydroxycorticosterone was potently inhibited by oleic acid. Thus, fatty acids are potent inhibitors of the 18-oxidase function of the mitochondrial enzyme P450(11) beta, whereas nonmitochondrial steroidogenic enzymes and the 11-hydroxylase function of P450(11) beta are relatively insensitive to fatty acids. The special sensitivity of aldosterone synthesis to fatty acid inhibition appears to result from the unusual susceptibility of the 18-oxidase function of the mitochondrial steroidogenic enzyme P450(11) beta. This mechanism would allow differential regulation of aldosterone vs. cortisol production by unesterified fatty acids. PMID- 8504750 TI - Identification by photoaffinity labeling of a membrane thyroid hormone-binding protein associated with the triiodothyronine transport system in rat erythrocytes. AB - Photoaffinity labeling with underivatized T3 was used to identify T3-binding proteins in the membrane of rat erythrocytes. UV irradiation of ghosts and peripheral protein-depleted membranes in the presence of [125I]T3 resulted in the covalent attachment of 125I to membrane proteins (analyzed by polyacrylamide gel electrophoresis and autoradiography). In the presence of the free radical scavenger dithiothreitol, 125I was selectively incorporated into a 45,000 mol wt band (p45) that was an integral membrane polypeptide. p45 photolabeling was half inhibited by 14 nM unlabeled T3. This concentration is similar to the Km for T3 transport in rat erythrocytes and the Kd of the high affinity T3-binding sites under equilibrium binding conditions in the rat erythrocyte membrane. T4 and tryptophan also strongly inhibited p45 labeling, whereas the D-isomer of T3 was less efficient, and leucine had no effect. This corresponds to the specificity of the system T-related T3 transport system and T3-binding sites of rat erythrocytes. The SH-reagent N-ethylmaleimide prevented p45 labeling, unless T3 was present to protect the T3 transport activity and the high affinity T3-binding sites from inactivation. No saturable labeling of p45 or other polypeptides was detected in membranes prepared from human erythrocytes, which have very low T3 transport activity and no measurable high affinity T3-binding sites. p45 is not disulfide linked and is not a degradation product of higher mol wt polypeptides. Substrates and specific inhibitors of known erythrocyte membrane transporters did not alter p45 photolabeling, indicating that p45 is not functionally related to these transporters. We conclude that the photoaffinity-labeled T3-binding protein p45 has the properties expected of the T3-binding component of the T3 transport system in rat erythrocytes. PMID- 8504751 TI - Identification and expression of G-proteins in human myometrium: up-regulation of G alpha s in pregnancy. AB - We report that human myometrium contains G alpha i1, G alpha i3, and G alpha q, and G alpha 11, which are expressed at similar levels in tissues from pregnant and nonpregnant women. G alpha i2 is also expressed, but at a slightly reduced level, in tissue taken from pregnant compared to nonpregnant donors. The major finding of this investigation is the substantial increase in G alpha s expression in pregnant myometrium. The increase in G alpha s levels may play a crucial role in maintaining relaxation of the uterus by favoring cAMP formation during pregnancy. PMID- 8504752 TI - Developmental regulation of protein kinase-A and -C activities in the baboon fetal adrenal. AB - We have previously demonstrated that the estrogen-regulated change in transuteroplacental metabolism of cortisol (F) and cortisone (E) from preferential reduction (E to F) at midgestation to oxidation (F to E) near term results in activation of the hypothalamic-pituitary-adrenal axis of the baboon and the ontogenesis of rate-limiting steroidogenic enzymes, culminating in de novo F secretion. It is well established that transcription of messages activated by peptide-mediated binding to membrane receptors can occur via cAMP-dependent protein kinase-A (PKA) and/or phospholipid/calcium-dependent protein kinase-C (PKC). The present study was designed to determine whether basal levels of PKA and PKC in the fetal adrenal are developmentally regulated during baboon gestation and, thus, could provide the mechanism(s) by which activation of the fetal adrenal near term is mediated. Fetal adrenal glands were obtained on day 100 (n = 8) and day 165 (n = 6) of gestation (term = day 184) from untreated baboons and on day 100 after treatment of the mother with estradiol benzoate, injected sc between days 70-100 to increase estrogen production. PKA activity (picomoles of 32P incorporated into kemptide per min/mg protein) was determined by incubation of adrenal cytosol (12,000 x g; 0.3-30 micrograms protein) in reaction mixtures containing 0.25 mM ATP, 1 x 10(6) dpm [lambda-32P]ATP, and 3 micrograms kemptide in the presence or absence of 0.02 mM cAMP. PKC activity (picomoles of 32P incorporated into histone IIIS per min/mg protein) was determined in cytosol (105,000 x g) and detergent-solubilized membrane fractions after incubation with 0.02 mM ATP, 50 micrograms histone IIIS, and 1 x 10(6) dpm [lambda-32P]ATP in the presence or absence of calcium and phospholipids. Mean (+/ SE) maternal serum estradiol concentrations (nanograms per ml) were 3-fold greater (P < 0.05) at term (1.9 +/- 0.3) than at midgestation and increased (P < 0.05) after treatment with estradiol. PKA activity was greater at term (3965 +/- 546) than at midgestation (2130 +/- 240) and increased (P < 0.05) 2-fold after treatment with estrogen (3525 +/- 416) at midgestation. PKC activity was always 3 to 4-fold lower than that of PKA and was similar in the cytosol and membrane fractions of the cell. In contrast to PKA, cytosolic PKC activity was similar at mid (265 +/- 98)-and late (353 +/- 99) gestation and was not altered by treatment with estradiol (223 +/- 27).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504753 TI - Steroid 17 alpha-hydroxylase and 17,20-lyase activities of P450c17: contributions of serine106 and P450 reductase. AB - Cytochrome P450c17 (EC 1.14.99.9) catalyzes both 17 alpha-hydroxylase and 17,20 lyase activities in mammalian steroidogenesis and also has some 16 alpha hydroxylase activity. The ratio of 17 alpha-hydroxylase to 17,20-lyase activity differs in the adrenal and testis and is developmentally regulated at adrenarche, but the nature of the enzyme's active site and the differential regulation of its two principal activities are unknown. The spontaneous human P450c17 mutation Ser106-->Pro eliminates all enzymatic activity. We used site-directed mutagenesis to construct expression vectors for the conservative P450c17 mutations Ser106- >Thr and Ser106-->Ala. When expressed in transfected COS-1 cells, these mutants retain only 20-30% of the 17 alpha-hydroxylase and 17,20-lyase activities, but retain 60% of the 16 alpha-hydroxylase activity of the Ser106 wild type. Thus, the amino acid occupying position 106 greatly affects enzymatic activity. Ser is found at position 106 in P450c17 in all mammals and birds studied, but the corresponding residue (position 112) in fish (trout) is Thr. Both the trout Thr112 wild type and a Thr112-->Ser trout mutant had equivalent 16 alpha hydroxylase, 17 alpha-hydroxylase, and 17,20-lyase activities, although these were only 5%, 5%, and 10%, respectively, of human Ser106. To catalyze its activities, P450c17 must receive electrons from NADPH via a flavoprotein termed P450 reductase. We examined the influence of the ratio of P450c17 to P450 reductase on enzymatic activity by cotransfecting COS-1 cells with varying amounts of vectors expressing each protein. The endogenous P450 reductase of COS 1 cells was sufficient to confer maximal 17 alpha-hydroxylase activity. P450 reductase produced from the transfected expression vector did not increase the conversion of [14C]progesterone to 17 alpha- or 16 alpha-hydroxyprogesterone, indicating that the endogenous immunodetectable P450 reductase of COS-1 cells was sufficient to confer maximal 17 alpha-hydroxylase activity. By contrast, the additional P450 reductase produced by the expression vector increased 17,20-lyase activity about 3-fold. Thus, the availability of reducing equivalents is a crucial factor in regulating 17,20-lyase activity. P450 reductase also increased the 17,20-lyase activity of the Thr106 and Ala106 mutants. These data suggest that the essential role of Ser106 is in the active site, rather than in interacting with P450 reductase, and that electron transfer may play an important role in regulating the 17,20-lyase activity of P450c17. PMID- 8504754 TI - Gonadotropin secretion, synthesis, and gene expression in human growth hormone transgenic mice and in Ames dwarf mice. AB - The expression of the mouse metallothionein-I (MT) promoter/human GH (hGH) fusion gene leads to reduced fertility and increased plasma LH levels in male MT/hGH transgenic mice. To determine the effects of hGH on gonadotropin synthesis and release, we have examined basal and GnRH stimulated LH and FSH release in pituitary incubations and perifusions; and pituitary content of LH, FSH, LH-beta messenger RNA (mRNA), and FSH-beta mRNA in MT/hGH transgenic males and in their normal littermates. For comparison, similar studies were performed in GH and PRL deficient Ames dwarf mice in which plasma gonadotropin levels are known to be reduced. We have also measured the LH and FSH release from normal pituitaries transplanted under the kidney capsule of MT/hGH transgenic or normal mice. We found that in MT/hGH transgenic mice, there were parallel increases in unstimulated and GnRH stimulated LH release from pituitary incubation, in pituitary LH content and in LH-beta mRNA levels. In pituitary perifusion, the basal LH secretion was elevated, whereas LH responses to GnRH pulses were not altered. In transgenic males, FSH-beta mRNA was increased, whereas basal and GnRH stimulated FSH release and pituitary FSH content did not differ from their normal controls. After normal pituitaries were transplanted to kidney capsules of MT/hGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the responsiveness to GnRH stimulation was maintained. In Ames dwarf mice, all gonadotropin content and release, as well as pituitary beta-mRNA contents were decreased. We conclude that in MT/hGH transgenic mice, the expression of LH-beta and FSH-beta gene is increased. In addition, there is a translational or posttranslational inhibitory influence on FSH synthesis. Although our previous studies suggest that the effects of hGH gene expression on LH and FSH release are exerted primarily at the hypothalamic level, the present results suggest existence of GnRH unrelated peripheral factors which can directly stimulate pituitary gonadotropin synthesis and release. In Ames dwarf mice, the deficiency of GH and PRL, as well as TSH, is associated with decreased LH-beta and FSH-beta gene expression which may account for the reduction in plasma gonadotropin levels. PMID- 8504755 TI - Regulation of osteoblastic gene expression by lead. AB - Although it is well recognized that lead accumulates in bone, skeletal tissue is considered primarily a sequestering compartment and not a site of toxic action for lead. However, exposure to lead is associated with impaired skeletal growth in children and reductions in indices of bone formation in laboratory animals. Osteoblastic ROS 17/2.8 cells were used in an effort to better understand the consequences of lead exposure on skeletal homeostasis. Studies on confluent cultures of ROS 17/2.8 cells revealed that lead (2-200 microM) had no effect on cell number or DNA and protein synthesis. However, alkaline phosphatase activity was reduced by lead in a dose- and time-dependent manner. Reductions in steady state alkaline phosphatase mRNA levels paralleled the lead-induced inhibition of enzyme activity. Moreover, lead exposure resulted in similar dose-dependent reductions in steady state type 1 procollagen and bone Gla protein mRNA levels. The effect of lead on osteoblastic gene expression in ROS 17/2.8 cultures, however, was selective in nature, as similar lead exposures resulted in no alterations in beta-actin or glyceraldehyde-3-phosphate dehydrogenase mRNA levels. These data demonstrate that lead, in the absence of over toxicity, specifically restricts the expression of certain aspects of the differentiated osteoblast phenotype. Such alterations in osteoblast function may contribute to the skeletal abnormalities observed in settings of lead intoxication. PMID- 8504756 TI - Tissue distribution of the human GLUT3 glucose transporter. AB - The tissue distribution of the GLUT3 glucose transporter protein was examined in human tissues using a rabbit antiserum directed against the C-terminal peptide sequence of human GLUT3. This anti-serum was shown to recognize the human GLUT3 protein in Chinese hamster ovary cells transfected with GLUT3 cDNA and to immunoprecipitate an authentic glucose transport protein in brain and testis membranes, as assessed by glucose-inhibitable photolabeling with [3H] cytochalasin-B. The GLUT3 protein, migrating with an apparent mol wt of approximately 48 kilodaltons, was strongly expressed in brain and testis membranes as well as in spermatozoa. It was not detectable in membranes from erythrocytes, adipocytes, heart, skeletal muscle, liver, kidney, spleen, thyroid, and prostate. Very low levels may be present in placenta. In brain, GLUT3 protein was strongly expressed in grey matter regions and was only weakly expressed in white matter, suggesting that it may be important in providing glucose to regions of high metabolic activity, i.e. to areas associated with synaptic transmission. None was found in peripheral (femoral) nerve. It appeared to be stable for up to 47 h in autopsy brain tissue kept at 4 C. The tissue distribution of human GLUT3 protein thus appears to be highly restricted (brain and testis/spermatozoa), in contrast with a previous report. Its function may be to provide a high affinity glucose transport system in cells that are highly dependent on glucose as a fuel source. PMID- 8504757 TI - Germ cell control of testin production is inverse to that of other Sertoli cell products. AB - Recent studies have shown that germ cells can regulate testins, two newly identified Sertoli cell proteins that are associated with junctional complexes. To investigate this possibility, several parameters of Sertoli cell function were investigated over 2-120 days post exposure of the rat testes to x-rays (3 Grays). The irradiation-induced loss of spermatogonia resulted in a maturation-depletion process progressively affecting all germ cell classes. Testis weight began to decrease when the most numerous germ cell type (spermatids) began to decline. A complete or near complete recovery of spermatogenesis and of the testis weight had occurred by day 120 post irradiation. There was no significant change in FSH, epididymal androgen-binding protein, and tubule fluid levels during the first weeks after irradiation, when the seminiferious epithelium was depleted of spermatogonia and germ cells up to early spermatids. In contrast, when the number of the more mature forms of spermatids declined (between day 21 and 54), FSH rose and androgen-binding protein as well as fluid production declined. The subsequent recovery of these parameters was also highly correlated with the number of late spermatids. By contrast, testicular testin contents reacted to the depletion of germ cells with a biphasic increase; a doubling occurred when spermatogonia, spermatocytes, and early spermatids were absent (days 4-28), and a 7-fold rise occurred by day 37 when the number of late spermatids had decreased by 50%. By day 54, when the sperm counts had reached a nadir, testin contents had returned to levels corresponding to about four times the control levels; they progressively recovered thereafter. These observations support the postulate that germ cells negatively regulate testins. This possibility was investigated with in vitro experiments showing that addition of germ cell-conditioned medium to Sertoli cell monolayers inhibited testin secretion in a dose-dependent manner. In conclusion this study; 1) highlights the complex interplay between the various germ cell classes in the control of the Sertoli cell function in the adult testis; 2) establishes that germ cell effects may be opposite on different Sertoli cell products; 3) demonstrates that several classes of germ cells negatively control testicular testin contents; and 4) emphasizes the particular role of late spermatids in Sertoli cell regulation. PMID- 8504758 TI - Coordinate transcriptional regulation of the three fibrinogen subunit genes by glucocorticoids in cultured primary liver cells from Xenopus laevis. AB - Xenopus laevis primary hepatocytes in culture are induced by glucocorticoid hormones to synthesize and secrete fibrinogen. The increase in production of the protein is preceded by a 10-to 30-fold elevation of the mRNAs coding for the three fibrinogen subunits, A alpha, B beta, and gamma. To analyze the mechanisms underlying this coordinate control of independent genes in a common regulatory network, we show here that the steroid hormone induced simultaneous activation of transcription of the three fibrinogen subunit genes. Using an optimized transcription run-on assay for nuclei from Xenopus primary liver cells, we demonstrate that glucocorticoids rapidly stimulated transcription of the A alpha fibrinogen subunit gene by 15- to 20-fold, the B beta gene by 5- to 10-fold, and the gamma gene by 5- to 15-fold. The three genes exhibited a highly concerted response to the hormone, in which maximal stimulation occurred by 30 min and was maintained for at least 16 h. Blocking new protein synthesis before hormone treatment reduced total transcription by 45% and partially inhibited specific hormonal induction of all three fibrinogen subunit genes. The effect of glucocorticoids on fibrinogen transcription, therefore, was dependent in part on ongoing protein synthesis, suggesting that hormonal stimulation uses already synthesized stable factors, but also requires labile or newly synthesized factors for the full effect. PMID- 8504759 TI - The flanking amino acids of the human follitropin beta-subunit 33-53 region are involved in assembly of the follitropin heterodimer. AB - Previous analyses of the topology of human follitropin (hFSH) with monoclonal antibodies and antipeptide antibodies have led to a current operating hypothesis that some amino acids within the hFSH beta 33-53 region are surface oriented, and others participate in subunit contact. Protein structural analysis predicts beta turns within this region, and the immunochemical studies indicate that the ends may be involved in subunit contact. In this study, hFSH beta was mutagenized to change 34TRDL37 to 34AAAA37 or 48QKTCT52 to 48AAACA52, allowing us to study the ends of the hFSH beta 33-53 sequence contiguous with the hFSH beta sequence. Wild type and mutant cDNAs were coexpressed with alpha-subunit cDNA in CHOPro-5 cells. Wild-type hFSH was secreted from cells cotransfected with wild-type hFSH alpha and hFSH beta cDNAs, as expected. However, heterodimeric hFSH was minimally detected in the medium from cells transfected with the 34TRDL37 mutant and was not detected in the case of the 48QKTCT52 mutant. Analysis of cell lysates (intracellular FSH) by immunoprecipitation and polyacrylamide gel electrophoresis showed that wild-type and mutant beta-subunits were indistinguishable and recoverable intact from each cell line. Additionally, analysis of lysates with a conformation-specific monoclonal antibody 3G3 revealed that similar levels of properly folded beta-subunit were produced in cells expressing wild-type or either mutated beta-subunit. These data indicate that the flanking amino acids of the hFSH beta 33-53 region, in particular 48QKTCT52, are critical for assembly of hFSH heterodimer. PMID- 8504760 TI - Characterization of a prolactin binding protein in rat serum. AB - To determine the presence of a PRL-binding protein (PRL-BP) in rat serum, female rats were ovariectomized and administered sc estradiol benzoate capsules. Serum was incubated with [125I]rat PRL (rPRL) for 1 h at 37 C with or without different doses of rPRL, ovine PRL (oPRL), or rGH. Separation of the [125I]rPRL-PRL-BP complex from unbound [125I]rPRL was accomplished by Sephadex G100 chromatography or by precipitation with an antibody against rat liver PRL receptor. Results showed that a protein was able to bind specifically to rPRL or oPRL, but not to rGH. Scatchard plots gave an affinity constant of 1.18 +/- 0.7 10(9) M-1 and a capacity of 11.24 +/- 1.4 nM. The complex [125I]rPRL-PRL-BP migrated in the void volume of sephadex G100 column, but with an apparent mol wt of 80K after cross linking and electrophoresis under reducing conditions. PRL BP was purified from estradiol-treated ovariectomized females by an oPRL sepharose 4B affinity column. Purified protein migrated under reducing conditions with apparent mol wt of 50K and 27K but of 160K under nonreducing conditions. After transfer on nitrocellulose filter, the 160K, 50K and 27K forms were able to bind to monoclonal antibodies directed against rat liver PRL receptor. The 160K and 50K were still able to bind to [125I]oPRL, but not the 27K. These results showed that rat serum contained a PRL-BP, which presented a strong homology to PRL receptor, at least for the immunological and binding characteristics. PMID- 8504761 TI - Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased Sertoli and germ cell numbers. AB - Our previous studies have shown that transient neonatal hypothyroidism, induced by treatment with the reversible goitrogen 6-propyl-2-thiouracil (PTU), increases testicular size and daily sperm production in the adult rat by up to 82% and 136%, respectively. The objective of the present study was to examine morphological and functional changes in adult seminiferous tubules associated with PTU-induced increases in testicular size and sperm production. Sprague Dawley rats were treated with PTU from birth to day 25 or left untreated; for morphometry, all testes were fixed by vascular perfusion at 90 days of age. Although testicular weight was increased 62% in treated rats, gross pathological changes were not evident in these organs, and spermatogenesis appeared morphologically normal. The percent area of testis occupied by seminiferous tubules was equal in control and treated testes, but mean seminiferous tubule diameter and length were increased in the PTU-treated testis. The adult number of Sertoli cells in treated testes was increased by 157%, and the numbers of leptotene spermatocytes and round spermatids were increased 84% and 93%, respectively. These results demonstrate that increases in Sertoli cell numbers result in increased sperm production and support the idea that Sertoli cells are the major regulators of the magnitude of sperm production. Although the round spermatid to Sertoli cell ratio was reduced by nearly 30%, the number of round spermatids per g testis was increased by 14%. This increased efficiency of sperm production was accomplished by an increased density of Sertoli cells along the basement membrane and an increased height of the seminiferous epithelium. Despite the large increase in Sertoli cell numbers in treated rats, Northern blot analysis using Sertoli cell-specific cDNA probes for transferrin and androgen binding protein indicated that relative steady state levels of mRNAs per Sertoli cell for these two secretory proteins were similar in control and treated rats at 90 days of age. PMID- 8504762 TI - Human placental 11 beta-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform. AB - Excess glucocorticoids impair fetal growth and cause teratogenesis. Placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the inactivation of cortisol to cortisone, preventing the high maternal cortisol levels from reaching the fetal circulation and thus preserving the low cortisol fetal environment. In previous work, an NADP-dependent isoform of 11 beta HSD has been purified from rat liver, a cDNA isolated, and the human homolog cloned. However, much evidence suggests tissue-specific 11 beta HSD activities that cannot be explained by the liver-type isoform. Therefore, we have partially purified human placental 11 beta HSD and compared it to the enzyme in rat liver. Human placental subcellular fractions exhibited NAD-dependent 11 beta HSD activity, but showed little activity with NADP. The enzyme had a pH optimum of 7-8.5 (peak, 7.7), was only sparingly soluble in detergents (solubility with Triton X-100 was very poor), and exhibited little latency or change in pH profile in detergent solution. By contrast, rat liver 11 beta HSD was exclusively NADP dependent and was easily solubilized by a wide range of detergents (including Triton X-100), revealing substantial latency and altered pH profile [optimum of 10, becoming 7-10 (peak, 9.5) in detergent]. These data do not merely reflect species differences, as rat placental 11 beta HSD was similar to the human placental isoform. AMP affinity chromatography, which was completely without affinity for rat liver 11 beta HSD, achieved a 1000-fold purification of human placental 11 beta HSD. This had Km values for corticosterone (mean +/- SE, 14 +/- 1 nM) and cortisol (approximately 55 nM) that were over 100 times lower than that for liver 11 beta HSD. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed identification of a band (apparent mol wt, 40,000) that correlated consistently with human placental 11 beta HSD activity (contrasting with a mol wt of 34,000 for rat liver 11 beta HSD). Thus, the NAD-dependent human placental 11 beta HSD is distinct from the previously characterized rat liver isoform and may be the product of a separate gene. PMID- 8504763 TI - Estrogenic actions of RU486 in hormone-responsive MCF-7 human breast cancer cells. AB - Previously, we demonstrated that the progestin components (19-nortestosterone derivatives) in oral contraceptives are able to stimulate human breast cancer cell proliferation via an estrogen receptor (ER)-mediated mechanism. We now examine RU486, an antiprogestin, to determine whether it has estrogenic properties because it is also a 19-nortestosterone derivative. We found that RU486 stimulated the growth of MCF-7 human breast cancer cells at a concentration of 10(-6) M, which is similar to the pharmacological concentration (micromolar range) found in women taking RU486. The antiestrogens 4-hydroxytamoxifen and ICI 164,384 blocked RU486-induced cell proliferation. The estrogenic activity of RU486 is not due to impurities or aromatization to estrogenic metabolites. To determine whether the proliferative action of RU486 was mediated through the ER, cells were transfected with a chloramphenicol acetyltransferase reporter gene under the control of an estrogen response element derived from the Xenopus laevis vitellogenin 2A gene. We found that RU486 was able to induce chloramphenicol acetyltransferase activity at the concentrations that stimulated cell proliferation, and this induction was blocked by the addition of 4 hydroxytamoxifen and ICI 164,384. The estrogenic potential of RU486 to regulate ER target gene expression was also investigated. We found that, like 17 beta estradiol (E2), RU486 was able to alter the expression and synthesis of progesterone receptor. The level of progesterone receptor (145 and 186 fmol/mg cytosol protein, respectively) was increased significantly compared to the control value (3 fmol/mg cytosol protein) with the addition of 10(-6) M RU486 or 10(-10) M E2, as determined by an enzyme immunoassay. The levels of transforming growth factor-beta 2 (TGF beta 2) and TGF beta 3 mRNA, but not TGF beta 1 mRNA, were decreased dramatically with the addition of 10(-6) M RU486. This is consistent with the effects of E2 on TGF beta expression. Therefore, RU486 has estrogen-like activities in its regulation of ER target gene expression. These results demonstrate that RU486 is a weak estrogen in human breast cancer cells and suggest that the RU486-induced cell proliferation is mediated via ER. The novel finding that RU486 exhibits some estrogen-like activity may be important for the interpretation of its action at high dosages as an abortifacient and also if RU486 is going to be evaluated clinically, again at high doses, for the treatment of breast cancer. PMID- 8504764 TI - Neurochemical regulation of hypothalamic oxytocin messenger ribonucleic acid levels during early lactation in rats. AB - The objective of the present studies was to investigate whether the stimulatory influence of the suckling offspring on the level of hypothalamic oxytocin (OT) messenger RNA (mRNA) in early lactation in rats is mediated by activation of the central noradrenergic and/or oxytocinergic systems, both of which have been strongly implicated in suckling-induced OT release. Experiments tested whether the effect of litter separation immediately postpartum to reduce hypothalamic OT mRNA could be mimicked by pharmacological disruption of either noradrenergic or oxytocinergic signals. Bilateral microinjections of the catecholamine neurotoxin 6-hydroxydopamine into either the supraoptic nucleus (SON) or paraventricular nucleus/anterior commissural nucleus regions significantly reduced the concentrations of norepinephrine in these areas, but did not alter the relative levels of OT mRNA in these regions, suggesting that the stimulatory inputs provided by the suckling offspring are not transmitted through the noradrenergic system. However, 24-h infusion of the OT antagonist desGLY-NH2, d(CH2)5 [Tyr (Me)2 Thr4]OVT into the third ventricle of rats maintaining their litters immediately postpartum reduced the level of OT mRNA in the SON. Conversely, chronic infusion of OT into the third ventricle of rats separated from their litters immediately postpartum attenuated the decline in OT mRNA in the SON. OT mRNA levels in the paraventricular nucleus/anterior commissural nucleus region did not change in response to litter separation, or infusion of OT or OT antagonist, implying differential regulation of OT mRNA expression in the magnocellular nuclei. The present results suggest that in addition to promoting OT secretion, OT released centrally by suckling may facilitate OT gene expression, at least during the early postpartum period when OT mRNA is subject to some degree of afferent regulation. PMID- 8504765 TI - Thyroglobulin molecules internalized by thyrocytes are sorted in early endosomes and partially recycled back to the follicular lumen. AB - Thyroglobulin (Tg) molecules stored in thyroid follicle lumens are heterogeneous in terms of iodine and hormone contents. It has been suggested that thyroid hormone is preferentially produced from the most highly iodinated Tg molecules and that thyrocytes are capable of selecting these molecules. The cellular localization as well as the molecular basis of such a selection process are not known. The present work was undertaken to determine whether there is selectivity at the step of endocytosis and, if not, to discover other possible mechanisms. Studies were conducted on reconstituted thyroid follicles (RTF) in culture. We compared the ability of thyrocytes to internalize Tg and an exogenous protein, BSA, which is neither iodinated nor glycosylated. To identify the protein, Tg and BSA were coupled to gold particles of different size and microinjected in a fixed ratio into the lumen of RTF. Neither of the two protein gold probes detected by transmission electron microscope bound at the cell surface, and both entered the cells at a similar rate and were concentrated in early endosomes. After 20 min, both Tg-G and BSA-G were segregated into distinct vacuolar structures. At 60 min, the intracellular content of BSA-G (mainly in prelysosomes and lysosomes) was 2- to 3-fold higher than that of Tg-G. At the same time, there was a marked reduction in the BSA-G/Tg-G ratio in the lumen. The differences between the Tg-G and BSA-G distribution patterns that were amplified in TSH-treated RTF are in keeping with a back-transfer of internalized Tg toward the lumen. The existence of a cell to lumen transport of previously endocytosed Tg was further documented using intralumenal [125I]Tg as a marker. RTF pulse labeled with tracer amounts of [125I]iodide were shortly incubated with TSH to induce [125I]Tg endocytosis, and the fate of internalized [125I] Tg was studied in a chase incubation period of up to 4 h. At 20 C, where the degradation of internalized Tg is blocked, we observed a time-dependent decrease in intracellular [125I]Tg and a corresponding increase in the lumenal [125I]Tg content. This cell to lumen [125I]Tg transfer was inhibited by primaquine. In conclusion, our data show that 1) the thyroid apical endocytic process does not exhibit selectivity for Tg; 2) the thyrocyte possesses a sorting machinery for endocytosed ligands; and 3) internalized Tg molecules can be recycled back to the follicular lumen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504766 TI - Relation between glucose-stimulated insulin secretion and intracellular calcium accumulation studied with a superfusion system of a glucose-responsive pancreatic beta-cell line MIN6. AB - The concept that cytosolic free calcium is the primary signal for insulin secretion is generally accepted, but studies with intact pancreatic beta-cells of the cytosolic free calcium concentration-insulin secretion relationship have produced contradictory and sometimes confusing data. We designed a superfusion system of a pancreatic beta-cell line, MIN6, loaded with fura-2, which allowed simultaneous measurement of cytosolic free calcium concentration and insulin secretion. MIN6 cells released insulin in response to high glucose, thus resembling events in normal islet cells. Cytosolic free calcium concentration and insulin secretion rapidly increased, and the increase was suppressed by mannoheptulose or by sodium azide. This increase was suppressed by lowering the temperature of the medium. Cytosolic free calcium concentration and the insulin secretion induced by leucine were not influenced by mannoheptulose but were inhibited by sodium azide. In RINm5F cells, cytosolic free calcium concentration and insulin release were slightly suppressed by glucose but were increased by ionomycin. There was a close relation between the rise in cytosolic free calcium concentration and insulin secretion in all cases. Our findings provide a direct evidence that a rise in cytosolic free calcium concentration depends on glucose metabolism and is a primary signal for insulin secretion. PMID- 8504767 TI - Regulation of glutamic acid decarboxylase diabetes autoantigen expression in highly purified isolated islets from Macaca nemestrina. AB - Macaca nemestrina, which may have larger and more numerous pancreatic islets than other species, was used for large scale islet isolation by ductal collagenase perfusion and Ficoll gradient centrifugation. The average yield was 51,000 islet equivalents per pancreas, or 8,750 islets equivalents per g. The average purity was 91%, often exceeding 95%. These are the highest reported size, purity, and yield per g of any nonautomated primate islet series. Perifusion with glucose, arginine, and isobutylmethylxanthine showed appropriate biphasic insulin secretion. Unlike that in the rat, human islet glutamic acid decarboxylase (GAD) isoform expression is restricted. However, glycemic regulation of GAD expression has been shown only in rats. We, therefore, tested hypotheses that M. nemestrina islets also have restricted GAD expression, that GAD expression in primates is stimulated by glucose, and that this stimulation remains restricted to the 64,000 mol wt (GAD65) isoform. Immunoprecipitation of labeled islet extracts showed that GAD65 expression increased 16.7 +/- 0.6-fold during high glucose in vitro culture. After controlling for observed increases in protein synthesis, specific glucose stimulation was still 4.2 +/- 0.2-fold. Specific antisera revealed no GAD67 expression under basal conditions, and isoform restriction was maintained during stimulation. Increased GAD65 synthesis thus accounts for glucose stimulation of 64K expression. These time- and concentration-dependent effects of glucose suggest that hyperglycemia increases autoantigenicity and may accelerate beta-cell destruction in primates, supporting a role for beta-cell rest in insulin-dependent diabetes mellitus prevention. PMID- 8504768 TI - Experimental diabetes mellitus in a teleost fish. I. Effect of complete isletectomy and subsequent hormonal treatment on metabolism in the goby, Gillichthys mirabilis. AB - The anatomical feature of a single pancreatic endocrine (islet) organ devoid of exocrine tissues and separated from other vital organs in the goby, Gillichthys mirabilis, allowed a relatively simple surgical isletectomy to be performed. Isletectomized (Ix) fish were then evaluated to determine whether the lack of islet hormones would cause the development of symptoms of insulin-dependent diabetes mellitus (IDDM) in a teleost fish. Isletectomy resulted in several symptoms typical of untreated IDDM in mammals. Plasma glucose was 3.5-fold higher in Ix animals (approximately 23 mmol/liter) than in intact and sham-Ix controls (6-7 mmol/liter), while urinary glucose was increased from less than 4 mmol/liter in controls to greater than 40 mmol/liter in Ix animals. Isletectomy also resulted in a significant elevation of plasma beta-hydroxybutyrate (from 0.7-0.8 to 1.0 mmol/liter). The severity of the metabolite imbalances was directly correlated with the degree of food consumption in Ix individuals, suggesting a reduced ability to assimilate dietary nutrients. In addition, distension of the abdomen due to increased food intake and a marked swelling of the urinary bladder suggested hyperphagia and polyuria, respectively, in the Ix animals. Insulin replacement therapy over 2 weeks corrected the glycosuria, polyuria, and hyperphagia and resulted in dose-related reductions in plasma glucose and beta hydroxybutyrate levels. Injection of Ix animals with GH, on the other hand, produced no significant changes in any of the metabolic parameters measured. The establishment of this unique model of IDDM in an ectothermic vertebrate should prove valuable for future comparative studies on the role of insulin and other pancreatic factors in the regulation of metabolic and growth processes. PMID- 8504769 TI - Experimental diabetes mellitus in a teleost fish. II. Roles of insulin, growth hormone (GH), insulin-like growth factor-I, and hepatic GH receptors in diabetic growth inhibition in the goby, Gillichthys mirabilis. AB - Insulin-dependent diabetes mellitus (IDDM), when untreated or poorly controlled in mammals, results in growth retardation. To determine whether the same relationship exists in an ectothermic vertebrate, IDDM-like symptoms were induced in a teleost fish, the goby Gillichthys mirabilis, by surgical removal of its pancreatic endocrine (islet) organ. Isletectomized (Ix) gobies lost body weight, their skeletal growth was retarded, as measured by changes in body length, and they exhibited a 50% reduction in cartilage 35SO4 incorporation in vitro, consistent with changes that occur in mammals with IDDM. Injections of bovine insulin into the Ix fish restored body growth parameters to control levels and stimulated cartilage 35SO4 incorporation in a dose-related manner. In contrast to mammals with IDDM, which are resistant to GH action, injection of teleost GH stimulated cartilage 35SO4 incorporation in the Ix fish. Furthermore, whereas cartilage from rats with IDDM is resistant to stimulation by insulin-like growth factor-I (IGF-I) in vitro, cartilage explants from the Ix fish were highly responsive to recombinant bovine IGF-I, exhibiting a dose-dependent stimulation of 35SO4 incorporation. As far as we are aware, these results represent the first demonstration of diabetic growth inhibition in an ectothermic vertebrate. This inhibition is similar to that which occurs in mammals with IDDM in some respects, but is different in others, as the diabetic fish did not develop resistance to growth stimulation by either GH or IGF-I. While these results support a role for insulin in maintaining the GH-IGF-I-growth axis in this ectothermic vertebrate, there may be important differences in the role of insulin in the promotion of anabolic processes. PMID- 8504770 TI - Insulin-like growth factor I gene expression by primary cultures of ovarian cells: insulin and dexamethasone dependence. AB - A growing body of information now supports the existence of a complete intraovarian insulin-like growth Factor I (IGF-I) system replete with ligands, receptors, and binding protein(s). However, studies concerned with the regulation of ovarian IGF-I gene expression remain scarce. It was thus the objective of this communication to evaluate the expression of the IGF-I gene in the immature rat ovary under in vitro conditions. Whole ovarian dispersates or isolated granulosa cells were cultured for up to 96 h under serum-free conditions in the absence or presence of the indicated experimental agents. Extracted total RNA was subjected to a sensitive solution hybridization/RNase protection assay using 32P-labeled rat IGF-I and/or type I IGF receptor antisense RNA probes. Cultured in the absence or presence of FSH (100 ng/ml), whole ovarian dispersates (or isolated granulosa cells) displayed time-dependent (FSH-independent) decrements in the relative abundance of IGF-I transcripts apparent as early as 3 h after the onset of culture. No evidence of recovery was apparent by 96 h of culture. The apparent lack of an FSH effect did not reflect diminished biopotency as attested to by the ability of the hormone to promote time-dependent increments in the accumulation of progesterone. Importantly, the apparent decrease in ovarian IGF-I gene expression proved to be IGF-I specific in that type I IGF receptor transcripts displayed a substantial and sustained (for up to 96 h) FSH-independent increase beginning at the 24-h time point. At no point were IGF-II transcripts detected. The apparent decrease in the expression of IGF-I did not reflect the lack of extracellular matrix support in that neither laminin, collagen, nor whole serum supported sustained ovarian IGF-I gene expression. Treatment of whole ovarian dispersates with pharmacological concentrations of either insulin (1 micrograms/ml) or dexamethasone (10(-7) M) did not reverse the decline in IGF-I gene expression. Importantly, however, the combined application of both insulin and dexamethasone resulted in virtually complete preservation of IGF-I gene expression, the relative abundance of the corresponding transcripts proving uniform throughout. Taken together, these in vitro observations reveal irreversible (FSH-independent) decrements in ovarian IGF-I (but not type I IGF receptor) gene expression, the preservation of which required the concurrent provision of both insulin and dexamethasone. PMID- 8504771 TI - Developmental assessment of hypothalamic tuberoinfundibular dopamine in prolactin deficient dwarf mice. AB - Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by visualization using formaldehyde-induced catecholamine histofluorescence and by quantification using catecholamine HPLC at selected postnatal ages (7, 14, 21, 30, and 90 days). Phenotypically normal (DF/?) littermate mice were compared with dwarfs by both methods at each age. The studies were designed to investigate whether the known deficiency in hypothalamic tuberoinfundibular DA in adult dwarfs is present neonatally or develops over the postnatal period. The anterior pituitary of each mouse was processed for GH and PRL immunocytochemistry. At 7 days of age, GH immunostaining was robust, and scattered PRL-positive cells were noted in DF/? pituitary. Homogeneously distributed PRL cells increased in number through 30 days of age in normal mice. Neither GH nor PRL immunoreactivity was present in df/df mice at any age. At 7, 14, and 21 days of age, hypothalamic DA tuberoinfundibular histofluorescence was comparable in df/df and DF/? mice. At 90 days of age, tuberoinfundibular histofluorescence in normal mice remained intense, but was virtually undetectable in dwarfs. The developmental change affected only tuberoinfundibular neurons, since DA histofluorescence in nonhypophysiotropic areas, such as substantia nigra (SN), was qualitatively comparable for df/df and DF/? for all ages examined. Norepinephrine (NE) fluorescence in hypothalamus was also comparable for df/df and DF/?. Catecholamine HPLC provided quantitative confirmation of histofluorescence observations. DA and NE levels in both hypothalamus and ventral midbrain, including SN, increased during development in both df/df and DF/? brains. NE levels were not different between dwarf and normal animals at any age in either medial basal hypothalamus (MBH) or SN. The DA concentration in SN was not different between df/df and DF/? at any age examined. MBH DA was comparable in df/df and DF/? mice at 7, 14, and 21 days of age; at 30 and 90 days, MBH DA was markedly lower (P < 0.001) in dwarf than in normal mice. Although MBH DA in dwarfs was comparable to that in normal mice at 21 days, the increase in dwarfs between 14 and 21 days was not statistically significant. Thus, the hypothalamic DA deficit that exists in adult dwarf mice is not present neonatally and represents a failure to increase DA compared with normal mice after 14 days of age. The failure of continued development of hypophysiotropic tuberoinfundibular DA neurons in dwarf mice is correlated chronologically with absent pituitary PRL production. PMID- 8504772 TI - Co-expression of type 1 angiotensin II receptor (AT1R) and renin mRNAs in juxtaglomerular cells of the rat kidney. AB - Physiological and ligand binding studies have shown that Angiotensin II (AII) exerts various functions along different segments of the nephron, via the type-1 receptor (AT1R), resulting in the control of glomerular filtration rate (GFR) and water and salt homeostasis. We have used the recently cloned AT1R cDNA to localize, by in situ hybridization, the cells expressing AT1R mRNA in the rat kidney. On serial sections, juxtaglomerular (JG) renin secreting cells, identified by hybridization with a renin cRNA probe, also co-express AT1R mRNA. The co-expression of AT1R and renin mRNAs in the same cells documents visually the direct feedback control of AII on renin secretion. AT1R mRNA was also present in known target cells for AII: proximal convoluted tubule, mesangium and vasa recta. PMID- 8504773 TI - Early thyroid hormone treatment in rats increases testis size and germ cell number. AB - By means of in vivo and in vitro approaches, we studied the effect of thyroid hormone on postnatal development of rat testis. T3 treatment in neonatal rats is associated with an increase of testis size of about 60%, compared to coeval controls. Increased number of both Sertoli and germ cells and enlarged diameter of seminiferous cords were found in hyperplastic testes. In the T3-treated group, TSH serum levels were low and a slight increase of FSH was found. In vitro treatment of neonatal testis fragments by 10(-7) M T3 for 3 days increased the number of gonocytes (P < 0.001 vs control) and decreased the percentage of degenerating germ cells (P < 0.001 vs control). In the adult testis, both in vivo and in vitro treatments with thyroid hormone did not induce morphological modifications, thus demonstrating that the critical window of thyroid hormone effectiveness coincides with the prepuberal period. Since thyroid hormone stimulates Sertoli cells to secrete growth factors and nutrients for germ cell development, we suggest that the increased testicular size and germ cell number following the T3 treatment is mediated by a direct hormonal effect on the somatic cell of the seminiferous epithelium. PMID- 8504774 TI - Role of brainstem structures in seizures initiated from the deep prepiriform cortex of rats. AB - Previous studies showed that brainstem seizures can still be evoked after transections that separate forebrain from brainstem. We sought to determine whether forebrain-evoked electrographic seizures require brainstem connections for initiation and generalization. Male Sprague-Dawley rats weighing 295-320 g implanted with epidural electrodes had brain transections placed at the pre-, mid , or postcollicular level. In experiment 1, the transections were limited to severing the brainstem, sparing the telencephalon laterally; these are referred to as "core" transections. In experiment 2, the transections severed the brainstem and also cut through the lateral telencephalon. These "extended" transections were either (a) bilateral, (b) unilateral (i.e., a hemitransection confined to one hemisphere), or (c) partial (sparing pathways ventral to the pretectal nuclei). All transections were performed under ether anesthesia, and seizures were initiated 3 h later by focal infusion of bicuculline (BIC) into the area tempestas (AT) through a previously implanted guide cannula. In experiment 1, bilateral forebrain electrographic seizures occurred in the complete absence of connections between forebrain and brainstem, showing that the brainstem is not required for forebrain-evoked seizures. In experiment 2, forebrain seizures evoked by BIC in AT were suppressed by bilateral extended transections which interrupted connections between AT and the caudal lateral telencephalon. Under these circumstances, application of carbachol with BIC reinstated the forebrain seizure response. These results indicate that carbachol application served to compensate for loss of an excitatory influence on AT resulting from the severing of connections with the caudal telencephalon. The demonstration of direct projections from entorhinal cortex to AT using Fluoro-Gold tracing together with the finding that extended brain transections caudal to the telencephalon do not suppress focally evoked forebrain seizures provided further support for the notion that AT afferents from the caudal telencephalon regulate the sensitivity of AT to BIC. The present findings provide further evidence that seizure substrates in the forebrain and brainstem are separable and independent. PMID- 8504775 TI - Evidence of secondary epileptogenesis in amygdaloid overkindled cats: electroclinical documentation of spontaneous seizures. AB - Twenty-four spontaneously occurring convulsive seizures were documented by closed circuit TV (CCTV)-EEG monitoring in 3 cats subjected to unilateral amygdaloid overkindling for < or = 2 years. Electroclinical manifestations suggested that the seizures originated in the kindled amygdala (AM) (10 seizures in 3 cats), contralateral AM (7 seizures in 3 cats), or ipsilateral frontal cortex (7 seizures in 1 cat). All seizures of AM origin except one occurred during sleep 23 h to 20 days after the last stimulation-induced kindled seizure and culminated in secondarily generalized seizures. The seizures of frontal cortical origin occurred during waking within 1 h of a kindled seizure and remained partial in nature. In seizures of AM origin, ictal patterns at the primary and secondary sites were mirror images of each other, but latency of onset of each seizure stage in seizures of secondary site AM origin was longer than that in seizures of primary site AM origin in 2 of the 3 animals. We conclude that the secondary epileptogenic functional alterations capable of producing clinical seizures do occur in AM-overkindled cats, but the seizures are not entirely independent of the primary kindled site. PMID- 8504776 TI - Olfactory bulb kindling in mice susceptible and resistant to ethanol withdrawal. AB - The relation between kindling and susceptibility to ethanol withdrawal seizures was investigated using withdrawal seizure-prone (WSP) and withdrawal seizure resistant (WSR) mice. These lines were developed by selective breeding to be prone and resistant, respectively, to handling-induced convulsions after chronic exposure to ethanol. Development of kindled seizures in response to electrical stimulation of the olfactory bulb was investigated in mice aged 2 and 8 months with no exposure to ethanol. Older WSP mice kindled more slowly than older WSR mice, requiring significantly more stimulations to reach the first stage 3 and the first stage 5 seizures. In younger mice, there was no significant difference between the two lines in the rate of kindling. The lower kindling rate in mature WSP mice is in contrast to their higher sensitivity to handling-induced convulsions on withdrawal from ethanol and other agents. This finding suggests that separate genetic factors underlie these two models of mouse seizures. PMID- 8504777 TI - Age-dependent cognitive and behavioral deficits after kainic acid seizures. AB - The long-term behavioral and cognitive effects of seizures at different ages were studied using the kainic acid (KA) seizure model. Rats of postnatal (P) ages (in days) 5, 10, 20, 30, and 60 were administered KA intraperitoneally (i.p.), which induced status epilepticus for several hours, or an equivalent volume of saline. Occurrence of spontaneous recurrent seizures (SRS) was then monitored for 3 months by a closed-circuit videotaping system. Rats began behavioral testing on P80; a separate group of rats that received KA on P60 began testing on P120. Behavioral tests included the Morris water maze (visuospatial learning and memory), the open field test (response to a novel environment), and the handling test (emotionality). When tested on P80, KA-treated P5 and P10 rats had no demonstrable deficits on any test as compared with controls. KA-Treated P20 rats differed from controls only on the water maze spatial bias test. KA-Treated P30 rats had deficits in spatial bias, were more active in the open field, and were more aggressive when handled. KA-Treated P60 rats, whether tested on P80 or P120, had deficits in learning platform position and spatial bias in the water maze, were more active in the open field, and were more aggressive when handled. P60 rats with SRS performed poorer in water maze place learning and spatial bias testing, although the number of SRS did not correlate with overall task acquisition. Our findings suggest age-related behavioral and cognitive deficits after KA-induced seizures. Pubescents and adults had alterations in learning, memory, exploratory behavior, and response to handling, whereas younger animals had no obvious behavioral or cognitive deficits. PMID- 8504778 TI - Decreased dopamine and increased norepinephrine levels in the spontaneously epileptic rat, a double mutant rat. AB - Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tm/+) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure. DA and NE levels were also determined in age matched male zitter, tremor and Kyo: Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10-12 weeks) SER, which showed epileptic seizures, and zitter rats than in adult Kyo: Wistar and tremor rats. DA levels in other areas such as thalamus-hypothalamus, midbrain, and pons medulla were not different among SER, zitter, tremor, and Kyo: Wistar rats at age 10-12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure-free SER (age 5 weeks) and young Kyo: Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo: Wistar rat, whereas in pons-medulla there was no difference between the two strains. In contrast, NE levels in the thalamus hypothalamus, midbrain, cerebellum and pons-medulla were higher in SER and zitter rats at age 10-12 weeks than in age-matched tremor and Kyo: Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons-medulla of young SER as compared with young Kyo: Wistar rats. Turnover rates of NE were significantly lower in pons-medulla and cerebellum of the adult SER than in those of Kyo: Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504779 TI - Pathogenic role of glutamate in hyperthermia-induced seizures. AB - Hyperthermia induces seizures in both humans and rodents, but the underlying mechanism remains unknown. The present study showed that hyperthermia, causing rapid increase in body temperature, increases the concentration of glutamate (Glu) released into a cortical perfusate before onset of seizures in rats and that this increase in Glu concentration correlated with a decrease in seizure threshold temperature. These results indicate that increased cortical extracellular Glu induced by hyperthermia contributes to onset of seizures. The same mechanism may be involved in clinical seizures induced by fever in patients with febrile convulsions or epilepsy. PMID- 8504780 TI - Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. AB - The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Age-adjusted incidence of epilepsy was 44 per 100,000 person-years. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged > or = 75 years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age-adjusted incidence of all unprovoked seizures was 61 per 100,000 person-years. Age- and gender-specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly. PMID- 8504781 TI - Validity of family history data on seizure disorders. AB - Accurate family histories of seizure disorders are important for both clinical practice and genetic research. This study evaluated validity of seizure histories of parents and siblings, obtained by interviewing 1,957 adults with epilepsy (probands). Probands were asked two questions to screen for occurrence of seizures in each relative; the first asked about epilepsy specifically, the second asked about "other seizures." For each relative who screened positive for seizures, a detailed clinical description was obtained. The final diagnosis was based on a review of all assembled information. Whenever possible, the proband's mother was interviewed independently about the family history, as were eligible relatives reported to have had seizures. Sensitivity, or the proportion of affected relatives who screened positive for seizures, was higher for epilepsy than for other seizures (87% vs. 32% assuming the mother's report to be correct, and 93% vs. 18% assuming self-report to be correct). For epilepsy, estimates of risk in siblings based on the final diagnoses were similar to previously reported findings in Rochester, Minnesota. For both isolated unprovoked seizures and acute symptomatic seizures, however, risk estimates were lower than in Rochester. These findings suggest that adults with epilepsy can report reasonably accurately about epilepsy in their parents and siblings, but isolated unprovoked seizures and acute symptomatic seizures are underreported. PMID- 8504782 TI - Seizure threshold in juvenile myoclonic epilepsy with Graves disease. AB - Thyroxine lowers the seizure threshold in experimental animals and humans. We report juvenile myoclonic epilepsy (JME) in two female patients with Graves' disease who had exophthalmos at age 11 (patient 1) and age 12 years (patient 2) but remained untreated until onset of seizures at ages 15 and 13 years, respectively. Seizures were not controlled well despite administration of antiepileptic drugs (AEDs) during the periods of excess serum thyroid hormones in Graves disease. When the serum levels of T3 were reduced to < 220 ng/dl with antithyroid drug treatment, both clinical seizures and paroxysmal EEG abnormalities disappeared despite discontinuation of AEDs and sleep deprivation. JME was noted only during periods of excess thyroid hormone and low compliance with antithyroid drug treatment. The excessively high level of thyroid hormones may have been a factor in precipitating the onset of JME. PMID- 8504783 TI - Parietal and occipital lobe epilepsy: a review. AB - There has been considerable recent interest in frontal lobe epileptic syndromes, and less attention paid to occipital and parietal epilepsies. The occipital and parietal lobes have arbitrary anatomical borders. The prinicpal seizure symptomatology includes somatosensory (paresthetic, painful, thermal, sexual, apraxia, disturbances of body image); visual (amaurotic, elementary and complex hallucinations, illusions) and other phenomena (anosognosia, apraxia, acalculia, alexia, aphemia, confusional states, gustatory, vertiginous, adversive, oculoclonic and eyelid flutter). The seizure symptoms are of varying localizing and lateralizing value and seizure discharges may spread rapidly and perceived symptoms may reflect secondary spread rather than the primary site of seizure onset. Recognized parietal and occipital epilepsy syndromes include benign epilepsy of childhood with centrotemporal spikes, benign epilepsy of childhood with parietal evoked spikes, benign occipital epilepsy of childhood, migraine/epilepsy syndromes, and epilepsy with bilateral occipital calcification. In addition, occipital and parietal epilepsy may be on the basis of any underlying structural lesion. There is frequently a poor correlation between clinical and EEG features. MRI and functional imaging often reveals underlying pathology. There have been no specific trials of different antiepileptic drugs for occipital and parietal seizures. Surgical treatment has its place, with attention to the risk of causing a fixed neurological deficit. PMID- 8504784 TI - Parietal lobe lesional epilepsy: electroclinical correlation and operative outcome. AB - We retrospectively studied ictal behavior, extracranial EEG, and operative outcome in 10 consecutive patients with intractable partial epilepsy of presumed parietal lobe origin who received a lesionectomy, i.e., resection of the neuroimaging-identified abnormality, at the Mayo Clinic. Nine patients had a pathologically verified foreign-tissue lesion, e.g., tumor or vascular malformation, and 1 patient had gliosis. All patients with foreign-tissue lesions were rendered seizure-free. The patient with gliosis experienced a reduction in seizure tendency. There were no operative complications. The most common seizure type was a simple partial seizure with visual, motor, or sensory symptoms (n = 8). Complex partial seizures (n = 5) and secondarily generalized tonic-clonic seizures (GTC, n = 2) were also observed. The ictal behavior was often nonspecific although useful in identifying lateralization of the epileptogenic zone. Extracranial interictal and ictal EEG changes were unreliable markers of the parietal lobe origin of seizure activity. Lesionectomy without chronic intracranial monitoring or functional mapping may be an effective and safe alternative surgical procedure in patients with partial epilepsy related to parietal lobe lesions. PMID- 8504785 TI - Epilepsy with bilateral occipital calcifications: Sturge-Weber variant or a different encephalopathy? AB - A series of cases of epilepsy with associated bilateral occipital calcifications (EBOC) without signs of phakomatosis and without any disorders known to produce cerebral calcifications have been reported. It is unclear whether EBOC is an incomplete variant of Sturge-Weber disease (SWD) or if it is a different, as yet undefined encephalopathy. We describe four new cases of EBOC that are different clinically by age of onset, type, course, severity of epilepsy, and associated cognitive deficits but that are linked by similar neuroradiologic findings. Similar to cases described in the literature, there is convincing evidence in favor of the hypothesis that these cases belong to an encephalopathy different from SWD and frequently associated with celiac disease. PMID- 8504786 TI - Identical morphology of the rolandic spike-and-wave complex in different clinical entities. AB - The morphology of the rolandic spike, the trough between the rolandic spike and the following slow wave, and of the slow wave itself was quantitatively studied in 43 children, classified into five clinical groups: (a) functional with epilepsy benign focal epilepsy of childhood with centrotemporal spikes (BECT) with oropharyngeal seizures or (b) BECT with unilateral or generalized seizures or (c) functional without epilepsy, and (d) organic with or (e) without epilepsy. The morphologic features of the rolandic spike-and-wave complex were identical in the five clinical categories. Thus, a quantitative description of the rolandic spike-and-wave complex can be given that is valid for the 43 children of the present study, although they represent a heterogeneity of associated clinical syndromes. The rolandic spike appeared to be not a spike but a sharp wave with a mean duration of 88 ms. In contrast to the opinion of several investigators, the morphology of the rolandic spike does not provide a clue to its "epileptogenicity" or to the presence or absence of an organic cerebral lesion in the individual child. In clinical practice, additional information (background activity of the EEG, computed tomography (CT) scan, or magnetic resonance imaging (MRI) of the brain) is needed to determine the significance of rolandic spikes occurring in the EEG of a child with respect to the probability of a cerebral lesion and the prognosis in relation to epileptic seizures. PMID- 8504787 TI - Anterior, total, and two-stage corpus callosum section: differential and incremental seizure responses. AB - Published reports suggest that control of generalized seizures is improved by callosotomy but do not necessarily indicate that completion of failed anterior callosotomy is beneficial. We studied 42 patients after anterior callosotomy and 22 after total callosotomy, of whom 14 underwent a two-stage procedure. Cure or marked diminution of seizures was most dramatic for atonic and tonic-clonic seizures after anterior callosotomy (100 and 83%), and for tonic-clonic and tonic seizures after total callosotomy (68 and 57%). For the 14 patients who failed to improve after anterior section and then underwent total section, incremental responses were noted for all seizure types, with cure or marked diminution of partial seizures in 2 of 14 patients, of tonic-clonic seizures in 6 of 10, of tonic seizures in 2 of 4, of atonic seizures in 2 of 5, and of myoclonic seizures in 1 of 1. More than two seizure types, verbal IQ < 80, and diffuse ictal EEG patterns were significantly more common in the anterior callosotomy failures. Total callosotomy can be of benefit when anterior callosotomy fails, especially for persistent tonic-clonic and tonic seizures, and will most often be necessary in patients with diffuse cerebral abnormalities. PMID- 8504788 TI - Ictal EEG changes with corpus callosum section. AB - Corpus callosum section diminishes but does not completely abolish secondary bilaterally synchronous interictal EEG discharges, yet often causes cessation of generalized seizures. The effects of corpus callosum section on ictal EEG patterns have not been described. We contrasted ictal EEG patterns before and after anterior callosotomy in 18 patients and before and after total callosotomy in 10 patients. Bilaterally synchronous seizure onset was disrupted in 5 of 11 anterior section patients and 5 of 5 total section patients. Seven of 18 anterior section patients and 5 of 10 total section patients had more localized seizure onset after the procedure; localization to the frontal lobe was observed after anterior or total section, but only total section patients had newly demonstrated posterior locations of seizure onset. These data suggest that the mechanisms by which bilaterally synchronous interictal and ictal discharges are generated differ. Although brainstem or diencephalic structures may contribute to formation of interictal bilateral synchrony, the corpus callosum may be the only pathway used in producing apparent bilateral synchronous seizure onset in patients with secondarily generalized seizures. PMID- 8504789 TI - Correlations between night sleep duration and seizure frequency in temporal lobe epilepsy. AB - Correlations between occurrence of complex partial seizures and altered sleep duration were analyzed in a small but strongly homogeneous population of temporal lobe epilepsy patients. Sleep deprivation and oversleep were determined individually; 682 epileptic seizures occurring on 4,995 days were related to occasional alterations of night sleep duration. The seizure-inducing effect of an actual relative sleep deprivation was 67-100% in four cases and 49-64% in four cases. Oversleep had no consistent seizure-provoking effect. Relative sleep deprivation may have a seizure-provoking effect, especially in temporal lobe epilepsy. This information may be used to instruct epileptic patients concerning sleep hygiene which might improve the efficacy of antiepileptic drug (AED) treatment, even if no change is made in medication. PMID- 8504790 TI - An in vitro study of focal epileptogenesis in combined hippocampal parahippocampal slices. AB - Brain slices from adult rats that included ventral hippocampus and adjacent parahippocampal areas were studied at various sites for the appearance of epileptiform discharges as extracellular potassium ([K+]o) was systematically varied over the range of 3 mM to 10 mM. The development of evoked epileptiform discharges (EEDs) and spontaneous epileptiform discharges (SEDs) was monitored in areas CA1, CA3, the hilus of the dentate gyrus (dentate hilus), the granule cell layer of the dentate gyrus (dentate gyrus), subiculum and entorhinal cortex. Increasing [K+]o elicited EEDs in a concentration-dependent manner. The entorhinal cortex and CA1 areas were most susceptible to this effect; the dentate gyrus was least susceptible. Increasing [K+]o also caused an increase in SEDs in all hippocampal areas. Separating entorhinal cortex from the rest of the slice by transections did not abolish discharges in any location. Lesions of the Schaeffer collaterals abolished discharges in CA1 but not in CA3. These findings demonstrate that changes in the extracellular milieu that are associated with epileptiform discharges in vivo are capable of eliciting paroxysmal discharges at multiple loci in the hippocampus and adjacent regions. Further, these findings demonstrate for the first time the intrinsic capacity of the entorhinal cortex to generate epileptiform discharges under in vitro ionic conditions known to occur in the intact brain during seizures. PMID- 8504791 TI - Rapid kindling with recurrent hippocampal seizures. AB - Kindling is a widely used model of epilepsy. While intriguing hypotheses have recently emerged about how kindling occurs, the mechanisms behind kindling remain to be elucidated. In order to test whether certain anatomical changes that have been detected in the brains of animals that have completed kindling are necessary for the expression of kindled seizures, means to achieve kindling over a time course too rapid for the anatomical changes to take place were sought. Stimulus trains of various durations (2 and 10 s) and frequencies (20, 50, and 100 Hz) were given every 30 min, 12 times a day for 4 consecutive days to rats through bipolar electrodes stereotactically positioned in the ventral hippocampus. Responses were monitored with conventional kindling behavioral seizure scores and afterdischarge durations. The frequencies studied were chosen to survey the range that has been previously used to determine the optimal frequency for eliciting maximal dentate activation. Maximal dentate activation is a paroxysmal process that has been postulated to play both a role in regulating epileptiform activity in the hippocampus and adjacent regions that are coupled in a functional hippocampal-parahippocampal loop and a role in kindling. All types of trains resulted in rapid kindling in which kindled motor seizures emerged after several stimuli and then were consistently elicited with each stimulus; there was also retention of the kindled state after periods of 18 h of withholding the stimuli. Thus, the overall response profile of the rapid kindling demonstrated in this study was phenomenologically similar to the profile of traditional kindling. Yet rapid kindling developed more quickly than did mossy fiber sprouting, determined in prior work, thereby excluding the latter as a necessary factor in rapid kindling. Stimulus frequency significantly influenced the rate of rapid kindling. Trains of 20 Hz, the optimal frequency for eliciting maximal dentate activation, yielded the fastest kindling. This finding supports the proposed role of maximal dentate activation and the hippocampal-parahippocampal loop in kindling. Longer (10 s) trains consistently triggered shorter afterdischarge durations. We postulate that this may reflect a tighter linkage between seizure-terminating processes with the 10 s trains than with 2 s trains. PMID- 8504792 TI - Differential effects of kindled and electrically induced seizures on a glutamate receptor (GluR1) gene expression. AB - To address the question of whether the mode of seizure induction contributes to the effects of seizures on glutamate receptor gene expression, we examined rat dorsal hippocampal slides by in situ hybridization after kindling by electrical stimulation of the amygdala, or after electrically induced tonic-clonic seizures. Levels of a glutamate receptor subtype (GluR1) mRNA were analyzed at three periods post kindled seizures and found to be decreased only in brains that were obtained 24 h after the last kindled seizure. This downregulation of GluR1 mRNA was transient and was observed only in animals that had behavioral manifestations after being electrically stimulated. It is probable that maintenance of the kindled state cannot be explained by a long-lasting change in GluR1 gene expression. Repeated electroshock-induced seizures increased GluR1 mRNA levels in the hippocampus. Our results show that mode of induction is an important determinant of the effects of seizures on the levels of expression of a glutamate receptor gene. PMID- 8504793 TI - Thalamic deficiency in norepinephrine release detected via intracerebral microdialysis: a synaptic determinant of seizure predisposition in the genetically epilepsy-prone rat. AB - Seizure predisposition in the genetically epilepsy-prone rat (GEPR) is caused by a combination of central nervous system abnormalities including deficiencies in the number of noradrenergic terminals and in the amount of norepinephrine (NE) released per terminal. Heretofore, estimates of a synaptic deficiency in NE concentration have been obtained from indirect indices. The present study uses intracerebral microdialysis to provide a direct demonstration of deficiency in extracellular NE levels in the GEPR brain. Under anesthesia, guide cannulae were stereotaxically placed over thalami of severe seizure GEPRs (GEPR-9s) and non epileptic control rats. After recovery from surgery, dialysis probes were inserted intrathalamically and the animals were allowed to move about freely. Artificial cerebrospinal fluid (ACSF) was perfused at 1 microliter/min and 30-min samples were collected for analysis on HPLC with electrochemical detection. Desipramine (5 microM in ACSF for 2 h), yohimbine (5 microM in ACSF for 2 h) or KCl (100 mM in ACSF for 1 h) was administered through the dialysis fiber after a stable NE baseline was established. Significantly diminished in vivo NE release from the thalamus was seen in response to all treatments in GEPR-9s when compared with non-epileptic controls. These observations coupled with earlier findings of deficits in postsynaptic receptor density and signal transduction support the hypothesis that noradrenergic transmission in the GEPR contributes to seizure predisposition through a failure to provide a normal level of protection against seizure initiation and spread. PMID- 8504794 TI - Antiepileptic drug treatment in a community health care setting in northern Ecuador: a prospective 12-month assessment. AB - The results of a prospective assessment of antiepileptic drug treatment carried out over a 12-month period, in the context of existing community health care in a rural area of a developing country (a highland region of northern Ecuador), are reported. A house to house survey defined all patients in the area with a history of epileptic seizures, and 192 patients with active epilepsy were recruited into the programme. These patients were randomised to treatment with carbamazepine or phenobarbital, and 139 completed the assessment. Treatment was carried out by health visitors and rural doctors, monitored by a team of neurologists, and standard treatment regimens were used. Treatment was effective in controlling seizures, 53% of the patients were rendered entirely seizure free in the second 6 months of therapy, and a further 14% had a 50% or more reduction in seizures. These results were similar to those reported in hospital based studies in developed countries. No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine. Antiepileptic drug levels were monitored during the study, and ranges similar to those found in developed countries were recorded. Compliance was good. In view of the successful treatment in this community control programme, we would recommend that community programmes for the control of epilepsy in rural settings should be given a higher priority in the planning of health care provision than is commonly the case. Finally, the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-standing epilepsy, who had not been previously treated, and the results of this treatment were good. PMID- 8504796 TI - Steady state pharmacokinetics of conventional versus controlled-release carbamazepine in patients with epilepsy. AB - The purpose of the present study was to compare the pharmacokinetic parameters of two carbamazepine (CBZ) tablet formulations (conventional (CBZ-CO) and controlled release (CBZ-CR)) in patients with epilepsy receiving the drug as monotherapy or polytherapy. The absorption rate constant (Ka), steady-state volume of distribution (Vdss) and total clearance (CL) were computed with the APIS software using 31 blood level profiles from 23 patients who were divided into four groups: patients receiving CBZ-CO in polytherapy, the same patients switched to CBZ-CR in the same polytherapy conditions, patients receiving CBZ-CO in monotherapy and patients receiving CBZ-CR in monotherapy. The four groups were compared in order to assess the significance of differences in Ka, Vdss, CL and diurnal fluctuations of plasma CBZ concentration. The results show a significant decrease of the Ka in the CBZ-CR groups compared to the CBZ-CO groups, both on monotherapy and on polytherapy. The comparison between the monotherapy and polytherapy groups shows increases of Vdss and CL, both in CBZ-CO and CBZ-CR polytherapy groups. Dispersion of pharmacokinetic data was higher in patients on CBZ-CO; among patients on CBZ-CR, dispersion was lowest in the monotherapy group. Clinical improvement was found in four of eight patients switched from CBZ-CO to CBZ-CR. CBZ-CR is therefore a valuable alternative to CBZ-CO. PMID- 8504795 TI - Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA. AB - The novel antiepileptic drug vigabatrin (Sabril) acts by inhibiting degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), increasing the GABA concentrations in the brain. Because the GABA degrading enzyme GABA aminotransferase (GABA-T) is also present in peripheral tissues, including blood platelets, measurement of plasma GABA levels might be a useful indication of the pharmacological response to vigabatrin during therapeutic monitoring. However, because of the very low concentrations of GABA in plasma, the few methods available for plasma GABA analysis are time-consuming, difficult to perform and/or not selective enough because of potential interference with other plasma constituents. In the present study, a rapid, selective and sensitive amino acid analysis HPLC method has been developed for plasma GABA determination with fluorescence detection, using o-phthaldialdehyde as a precolumn derivatizing agent. By employing a 3 microns particle size reversed-phase column and a multi step gradient system of two solvents, the very low endogenous concentration of GABA in human plasma could be reproducibly quantitated without interference of other endogenous compounds. Incubation of human plasma samples with GABA degrading enzyme(s) resulted in an almost total loss of the GABA peak, thus demonstrating the specificity of the method for GABA analysis. In addition to GABA and other endogenous amino acids, the HPLC method could be used to quantitate plasma levels of vigabatrin. Thus, this improved HPLC amino acid assay might be used to examine whether concomitant monitoring of plasma GABA and vigabatrin is useful for clinical purposes. This was examined in 20 epileptic patients undergoing chronic treatment with vigabatrin. The average plasma GABA level of these 20 patients did not differ significantly from non-epileptic controls. However, when epileptic patients were subdivided according to their clinical response to vigabatrin, vigabatrin responders had significantly higher GABA levels than nonresponders or controls. In contrast to the difference in plasma GABA, vigabatrin responders and nonresponders did not differ in dose or plasma level of vigabatrin. These data may indicate that determination of plasma GABA is a valuable non-invasive method for therapeutic monitoring in patients on medication with vigabatrin. PMID- 8504797 TI - cDNA cloning and mitochondrial import of the beta-subunit of the human electron transfer flavoprotein. AB - We have isolated a cDNA clone which encodes the entire beta-subunit of human electron-transferring flavoprotein (ETF) by screening an expression library from human liver using polyclonal antibodies against porcine ETF. This cDNA encodes a protein of 255 amino-acid residues with a predicted molecular mass of 27,877 Da which shows a high degree of similarity with partial amino-acid sequences obtained from both rat liver and Paracoccus denitrificans beta-ETF. Northern-blot analysis shows that the human beta-ETF mRNA is approximately 1 kb in size and is abundant in liver, heart and skeletal muscle. Incubation with intact mitochondria indicates that the cDNA-encoded beta-ETF polypeptide contains the information necessary to reach the mitochondrial matrix. These data are in agreement with previous experiments suggesting that beta-ETF, unlike the majority of nuclear encoded mitochondrial matrix proteins, does not have a cleavable leader peptide. Furthermore, when valinomycin is added to the incubation mixture, the import is abolished, thus demonstrating that it is an energy-dependent process. Interestingly, the sequence analysis of beta-ETF protein identifies a 26.3% identity with the Fix A gene product of the nitrogen-fixing bacterium Azorhizobium caulinodans. PMID- 8504798 TI - Evidence for a ternary interaction between alpha-actinin, (meta)vinculin and acidic-phospholipid bilayers. AB - The cytoskeletal component vinculin has been demonstrated by hydrophobic photoradiolabelling, to insert into bilayers containing acidic phospholipids and trace amounts of a photoactivatable analogue of lecithin. It is shown in this study that the higher-molecular-mass variant metavinculin and alpha-actinin, also share this property. alpha-Actinin and vinculin were also shown to associate with phosphatidylserine liposomes by chromatography of protein/lipid mixtures on a Bio Gel A-5m column. Furthermore, interesting differences in the behaviour of binary mixtures of these proteins, in the presence of phosphatidylserine liposomes, are shown. Thus, incubation of alpha-actinin with vinculin or metavinculin, prior to the addition of liposomes, strongly inhibited the photoradiolabelling of alpha actinin under conditions in which the liposome surface was non-limiting, but enhanced the labelling of vinculin. In contrast, vinculin and metavinculin did not mutually influence their labelling. Using gel-filtration chromatography, it was shown that alpha-actinin still bound to the vinculin-liposome complex, under conditions similar to those used for hydrophobic photolabelling with a non limiting lipid surface. In the presence of limiting amounts of liposomes, the alpha-actinin/vinculin ratio was markedly decreased in the liposome fractions. Our results suggest the formation of a ternary complex consisting of vinculin, alpha-actinin and phospholipids. In this complex, both proteins interact at the bilayer, resulting in an altered conformation of the two proteins and, as a consequence, in modified bilayer interactions. PMID- 8504799 TI - Chemical structure of the core region of Campylobacter jejuni serotype O:2 lipopolysaccharide. AB - The complete structure for the core region of Campylobacter jejuni serotype O:2 lipopolysaccharide (LPS) was assigned through studies on derivatives of the liberated oligosaccharide (OS 2) and the intact LPS. Structure determinations were performed using 1H-NMR spectroscopy, methylation studies supported by fast atom-bombardment mass spectrometry and linkage analysis by gas chromatography/mass spectrometry, Smith degradation, and oxidation with chromium trioxide. It was concluded that complete oligosaccharide chains had the following structure: [formula: see text] PMID- 8504800 TI - Coordinate changes in the expression of troponin subunit and myosin heavy-chain isoforms during fast-to-slow transition of low-frequency-stimulated rabbit muscle. AB - The purpose of this study was to follow the time course of changes in the expression of myosin heavy chain (HC) and troponin (Tn) subunit isoforms during fast-to-slow transition as induced in rabbit fast-twitch muscle by low-frequency stimulation. The evaluation of changes in the relative concentrations of myosin and troponin subunit isoforms were supplemented by measurements of relative protein synthesis rates using an in situ labeling technique. Changes in the amounts of mRNA encoding fast troponin C (TnC) were followed by Northern blot analysis, those for fast and slow troponin I (TnI) by in vitro translation of total RNA. The various fast myosin heavy chain (HC) and fast troponin T (TnT) isoforms were exchanged sequentially. Myosin HCIId which is the predominant fast isoform in rabbit tibialis anterior, was exchanged with HCIIa and, finally, the latter was replaced by the slow myosin HCI. The replacement of HCIId by HCIIa was accompanied by an exchange of TnT1f and TnT2f with TnT3f. The expression of HCI was accompanied by an exchange of TnT3f with the slow TnT isoforms, TnT1s and TnT2s. The changes in the relative concentrations of the TnT isoforms were preceded by similar changes of their relative synthesis rates. Pronounced decreases in the fast TnI and TnC isoforms occurred only with prolonged stimulation and were preceded by changes of the specific mRNAs and decreases in relative synthesis rates. The parallel time courses of the sequential transitions in both the myosin heavy chain and troponin T isoforms suggest the existence of coordinate programs of expression serving specific functional requirements. PMID- 8504801 TI - Role of tyrosine 129 in the active site of spinach glycolate oxidase. AB - The enzymatic properties and the three-dimensional structure of spinach glycolate oxidase which has the active-site Tyr129 replaced by Phe (Y129F glycolate oxidase) has been studied. The structure of the mutant is unperturbed which facilitates interpretation of the biochemical data. Y129F glycolate oxidase has an absorbance spectrum with maxima at 364 and 450 nm (epsilon max = 11400 M-1 cm 1). The spectrum indicates that the flavin is in its normal protonated form, i.e. the Y129F mutant does not lower the pKa of the N(3) of oxidized flavin as does the wild-type enzyme [Macheroux, P., Massey, V., Thiele, D. J., and Volokita, M. (1991) Biochemistry 30, 4612-4619]. This was confirmed by a pH titration of Y129F glycolate oxidase which showed that the pKa is above pH 9. In contrast to wild type glycolate oxidase, oxalate does not perturb the absorbance spectrum of Y129F glycolate oxidase. Moreover oxalate does not inhibit the enzymatic activity of the mutant enzyme. Typical features of wild-type glycolate oxidase that are related to a positively charged lysine side chain near the flavin N(1)-C(2 = O), such as stabilization of the anionic flavin semiquinone and formation of tight N(5)-sulfite adducts, are all conserved in the Y129F mutant protein. Y129F glycolate oxidase exhibited about 3.5% of the wild-type activity. The lower turnover number for the mutant of 0.74 s-1 versus 20 s-1 for the wild-type enzyme amounts to an increase of the energy of the transition state of about 7.8 kJ/mol. Steady-state analysis gave Km values of 1.5 mM and 7 microM for glycolate and oxygen, respectively. The Km for glycolate is slightly higher than that found for wild-type glycolate oxidase (1 mM) whereas the Km for oxygen is much lower. As was the case for wild-type glycolate oxidase, reduction was found to be the rate limiting step in catalysis, with a rate of 0.63 s-1. The kinetic properties of Y129F glycolate oxidase provide evidence that the main function of the hydroxyl group of Tyr129 is the stabilization of the transition state. PMID- 8504802 TI - gamma-Butyrobetaine hydroxylase. Structural characterization of the Pseudomonas enzyme. AB - gamma-Butyrobetaine hydroxylase is a 2-oxoglutarate-dependent dioxygenase that catalyzes the hydroxylation of gamma-butyrobetaine to carnitine, the last step in the biosynthesis of carnitine from lysine. The primary structure of the enzyme from Pseudomonas sp. AK1 has been determined. Sequence analysis of the intact protein and of peptides from essentially three different digests established the presence of a peptide chain containing 383 residues, and an N-terminal truncated form of 382 residues. The two chains have molecular masses of 43,321 Da and 43,207 Da, respectively, and are identical except for the presence or absence of an N-terminal asparagine residue; the shorter form starts with an alanine residue. In preparations of the dimeric protein, the two chains occur in an approximate ratio of 1:1. There are nine cysteine residues and 13 histidine residues, i.e. amino acids which have been postulated as ligands for iron binding. In spite of functional similarities, there appears to be no clear sequence similarities with any of the other mammalian 2-oxoglutarate-dependent dioxygenases so far characterized. PMID- 8504803 TI - Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and chromosomal localization of the gene. AB - We report the primary structure of 4-hydroxyphenylpyruvate dioxygenase [4 hydroxyphenyl-pyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating)]. The work is based on the isolation of cDNA clones from human liver lambda gt11 libraries. Several overlapping clones covering the coding sequence were characterized. In parallel, peptides from four different digests of the purified protein were analysed for their amino-acid sequence. These peptide sequences covered 86% of the cDNA-derived amino-acid sequence. This gives the sequence for a polypeptide of 392 amino acids with a calculated molecular mass of 44.8 kDa. There is more than 80% identity between the human and the pig enzymes and also between these enzymes and the F antigen from rat and the two allelic forms of this antigen from mouse. The enzyme has 53% conserved amino acids and 27% identical amino acids in common with 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. P.J. 874 and 52% conserved and 28% identical residues, with a protein from Shewanella colwelliana. At the C-terminus there is 61% identity between the seven proteins. These results indicate that these proteins are all 4 hydroxyphenylpyruvate dioxygenases. The identity of the C-terminus makes this part of the molecule a candidate for a functional role in the catalytic process. At conserved positions in all seven enzymes, there are two tyrosine residues and three histidine residues, i.e. amino acids which have been implicated as ligands for iron in 2-oxoacid-dependent dioxygenases. The gene encoding the enzyme was localized to chromosome 12q14-->qter by Southern-blot analysis of human-rodent somatic-cell hybrids. PMID- 8504804 TI - The primary structure of branched-chain alpha-oxo acid dehydrogenase from Bacillus subtilis and its similarity to other alpha-oxo acid dehydrogenases. AB - The bfmB mutant of Bacillus subtilis requires branched short-chain carboxylic acids for growth because the organism is known to be defective in branched-chain alpha-oxo acid dehydrogenase. The DNA in the region of bfmB has now been cloned and sequenced, and the gene has been analyzed. The results show that there are three open reading frames in the area, each of which is preceded by a putative ribosome binding site, and the last of which is followed by a putative transcription termination site with inverted repeats. The amino acid sequences deduced by analysis of the reading frames are highly similar (with 32-49% identity) to the E1 alpha, El beta and E2 components of pyruvate, 2-oxoglutarate and branched-chain alpha-oxo acid dehydrogenases from different sources. The thiamin diphosphate binding, putative subunit interaction and phosphorylation sites of the E1 alpha of four reported branched-chain alpha-oxo acid dehydrogenases from different sources are very similar to those of the first open reading frame (E1 alpha) of bfmB. A similar result is also obtained with the lipoyl-binding site (lysine) and its domain of the E2 component of alpha-oxo acid dehydrogenases from different sources. The present data, along with the reported biochemical data, lead to the conclusion that bfmB encodes a branched-chain alpha oxo acid dehydrogenase, which is composed of E1 alpha, E1 beta and E2 genes. This organization is identical to that of the 2-oxoglutarate dehydrogenase in B. subtilis. PMID- 8504805 TI - Rapid phosphorylation of 28-kDa heat-shock protein by treatment with okadaic acid and phorbol ester of BALB/MK-2 mouse keratinocytes. AB - Protein phosphorylation by okadaic acid and 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined using quiescent cultures of BALB/MK-2, a cell line derived from mouse epidermal keratinocytes. Treatment with okadaic acid caused rapid phosphorylation of five proteins with molecular masses of 65, 55, 50, 28 and 15 kDa (p65, p55, p50, p28, p15, respectively) while TPA caused rapid phosphorylation of five proteins with molecular masses of 80, 70, 40, 34 and 28 kDa (p80, p70, p40, p34, p28, respectively). In the present study, we examined p28, a common target protein of okadaic acid and TPA. The phosphorylation of p28 increased depending on time of exposure and doses of okadaic acid and TPA. Combined treatment with okadaic acid and TPA resulted in an additive effect. Its position on two-dimensional gel electrophoresis suggested that p28 is the 28-kDa heat-shock protein (HSP28). This possibility was confirmed by migration of p28 with HSP28 and comparative peptide mapping of the two proteins. The phosphoamino acid residue of phosphorylated HSP28 was serine. In two-dimensional tryptic peptide maps, the same peptides were phosphorylated after treatment with both okadaic acid and TPA. PMID- 8504806 TI - Different isoforms and stock-specific variants of the cell adhesion molecule C CAM (cell-CAM 105) in rat liver. AB - C-CAM is a cell adhesion molecule of the immunoglobulin superfamily with homophilic binding properties. Here we used the polymerase chain reaction to isolate clones of C-CAM from a rat liver cDNA library. Sequence analyses identified two major isoforms, C-CAM1 and C-CAM2, which differed in their 3' ends. C-CAM2 lacked a sequence of 53 nucleotides that was present in C-CAM1. This causes a frame shift and new stop codons, which gives rise to cytoplasmic domains of different sizes in the two isoforms (10 versus 71 amino-acid residues). In addition, all the clones had a different nucleotide and deduced amino-acid sequence (variant b) in the most N-terminal of the four immunoglobulin-like domains, compared to a previously published C-CAM sequence (variant a). Northern blot analyses with specific oligonucleotide probes demonstrated that two different rat stocks expressed either variant a or variant b. Northern-blot analyses of rat liver and lung also showed that at least five different C-CAM transcripts are produced. Two major mRNA size classes of 4.0 kb and 6.0 kb, and one minor class of 3.0 kb were found. Both the 4.0-kb and 3.0-kb messenger classes reacted with two different probes that could distinguish between C-CAM1 and C-CAM2, while the 6.0-kb population only reacted with the probe selective for C-CAM1. Taken together these data demonstrate the existence of four different protein-coding sequences of rat liver C-CAM (C-CAM1 a and b, and C-CAM2 a and b). We suggest that both allelic variation and alternative splicing may contribute to the isoform-expression pattern of C-CAM in rats. PMID- 8504807 TI - A cold-inducible Bombyx gene encoding a protein similar to mammalian sorbitol dehydrogenase. Yolk nuclei-dependent gene expression in diapause eggs. AB - To facilitate the study of the induction of sorbitol dehydrogenase by acclimation to 5 degrees C in diapause eggs of the silkworm, Bombyx mori, two cDNA libraries from eggs and larval fat bodies were screened with anti-(sorbitol dehydrogenase) serum, and a positive cDNA was cloned from the fat-body cDNA library. 1039 nucleotides determined from the cDNA corresponded to a protein-coding region consisting of 346 amino acids. The missing regions (containing two amino acids at the 5' end and a stop codon at the 3' end) were supplemented with the genome sequence. The deduced amino-acid sequence had 45-47% identity with mammalian sorbitol dehydrogenases. The results led us to conclude that the cDNA for a Bombyx homolog of mammalian sorbitol dehydrogenase was isolated, which was designated as BmSDH. Analyses of Northern hybridization and reverse transcription/polymerase chain reaction showed that the transcript of BmSDH occurred after chilling for 40-50 days when the diapause eggs were exposed to 5 degrees C from two days after oviposition to break the diapause. The changing pattern in the amount of BmSDH transcript was well correlated with those in the activity of sorbitol dehydrogenase and the amount of the enzyme protein in diapause eggs. Further, the transcript of BmSDH was localized in yolk cells. The results indicate that the yolk nuclei-dependent gene expression of BmSDH is induced by acclimation to 5 degrees C in diapause eggs. PMID- 8504808 TI - A comparative laser-flash absorption spectroscopy study of Anabaena PCC 7119 plastocyanin and cytochrome c6 photooxidation by photosystem I particles. AB - Laser-flash absorption spectroscopy has been used to investigate the kinetics of electron transfer from reduced cytochrome c6 and plastocyanin, isolated from Anabaena PCC 7119, to oxidized P700 in photosystem-I particles isolated from the same cyanobacterium and from spinach. For all metalloproteins and photosystems, the observed rate constant has a non-linear protein-concentration dependence, thus suggesting complex formation preceding electron transfer. Plastocyanin and cytochrome c6 have similar association constants for complex formation with spinach photosystem I, but the copper protein exhibits a higher intracomplex electron-transfer rate constant (twofold). With Anabaena photosystem I, the two redox proteins are more effective with respect to both complex formation (5-10 fold) and electron transfer (1.5-4-fold) than with the spinach photosystem. In all cases, the observed rate constants for electron-transfer monotonically decrease with increasing NaCl or MgCl2 concentration. This is interpreted in terms of the involvement of attractive electrostatic interactions, which result in the initial collision complex having the most productive orientation for the electron transfer process, without a requirement for further reorientation. The magnitude of the response to MgCl2 suggests the occurrence of specific ion effects as well. In the absence of added salts, the reduction rate of oxidized P700 increases with pH from approximately 6 to 8, but decreases slightly at pH 8.5. PMID- 8504809 TI - Immobilization of the tetrameric and monomeric forms of pigeon liver malic enzyme on Sepharose beads. AB - Pigeon liver malic enzyme was chemically attached to Sepharose 4B-CL beads. The enzyme lost approximately 50% of its original activity when immobilization was carried out with 5 mg CNBr/ml gel. Immobilization performed at pH 8.0 or pH 4.5 resulted in the formation of matrix-bound tetramer and monomer, respectively. Matrix-bound reconstituted tetramer was derived from matrix-bound monomer by mixing the latter with soluble enzyme at pH 4.5, then raised the pH of the solution to 8.0. The matrix-bound monomer was demonstrated to be enzymically fully active in terms of specific activity. The pH profile for the enzymic reaction was similar for both soluble and immobilized enzymes. However, the latter had a broader range for the optimum pH (pH 6.8-7.8). The Arrhenius plots for all immobilized enzyme forms were biphasic with inflection at approximately 27 degrees C. The apparent Michaelis constants for the substrates increased about 2-3-fold after immobilization. All immobilized enzyme forms, including the matrix bound monomer, showed substrate inhibition at high concentrations of L-malate. Both high-affinity and low-affinity binding sites for Mn2+ existed for all immobilized enzyme forms. These results are consistent with an existing asymmetric model, but are not compatible with a sequential model for the enzyme tetramer. The immobilized enzyme was stable for at least four months at 4 degrees C. As compared to soluble enzyme, the immobilized enzyme was less inhibited by (NH4)2SO4 or NaCl. It was also resistant to inactivation with periodate-oxidized aminopyridine adenine dinucleotide phosphate, an affinity label for malic enzyme. Incubation of the immobilized enzyme (1.25 microM) with the reagent (5.6 mM) resulted in pseudo-first-order inactivation with a rate constant of 0.0108 min-1 that was at least an order of magnitude smaller than that for the soluble enzyme. PMID- 8504810 TI - Prostaglandin-E1-binding sites in rabbit erythrocyte membranes. AB - Prostaglandin E1 (PGE1) binding sites have been identified on rabbit erythrocyte membranes. The binding of PGE1 to the membranes was found to be highly specific, reversible, and saturable. The high-affinity binding sites had a dissociation constant (Kd.1) of 5.6 +/- 1.2 nM with a binding capacity of 210 +/- 51 fmol/mg protein, whereas the low-affinity binding sites had a dissociation constant (Kd.2) of 22 +/- 6.4 microM, and a binding capacity of 321 +/- 78 pmol/mg protein. Incubation with PGE1 did not activate adenylate cyclase in the membranes. Preincubation of rabbit erythrocyte membranes with physiological amounts of insulin (1.5 nM) resulted in an increase of PGE1 binding to the membranes from 241 +/- 65 to 429 +/- 85 fmol/mg protein. The insulin-induced increase in PGE1 binding was due to an increase in binding sites (both high affinity and low-affinity binding sites) rather than to an increase in the affinity of the binding sites. Treatment of erythrocyte membranes with PGE1 at concentrations (4.0-7.5 nM) which were within the Kd.1 value of the high-affinity binding sites, resulted in a significant reduction in membrane fluorescence anisotropy (0.27 +/- 0.005-0.21 +/- 0.003). Use of higher concentrations (> 15 nM) of PGE1 reversed the effect of its lower concentration on the membrane anisotropy. PMID- 8504811 TI - NMR and molecular modeling studies of the interaction of berenil and pentamidine with d(CGCAAATTTGCG)2. AB - The interaction of two anti-trypanosomal agents, berenil and pentamidine, with the A+T-rich dodecamer d(CGCAAATTTGCG)2 has been examined by high-resolution 1H NMR, optical spectroscopy, and molecular modeling. Proton assignments for the free DNA and each DNA-ligand complex were obtained using nuclear Overhauser enhancement spectroscopy and total correlation spectroscopy. Complexation induces large changes in chemical shift for protons in the DNA minor groove for the A5-T9 segment, and intermolecular NOEs reveal contacts between the DNA bases and each ligand. The asymmetric binding site for berenil indicated by the NMR data suggests that at least two overlapping sites are involved. Rapid exchange between symmetrically-equivalent binding sites, via dissociative rearrangement, is consistent with retention of twofold degeneracy for both the ligand and the DNA host. Calculations of binding energy confirm that this DNA duplex contains overlapping sites of similar binding affinity. In contrast, the larger pentamidine molecule occupies a site that spans four or five bp, with asymmetric binding to the minor-groove 5'-ATTT sequence. The B-type conformation of the DNA is not altered substantially by either ligand. PMID- 8504812 TI - Primary structures of the N-linked carbohydrate chains from honeybee venom phospholipase A2. AB - The N-linked carbohydrate chains of phospholipase A2 from honeybee (Apis mellifera) were released from glycopeptides with peptide-N-glycanase A and reductively aminated with 2-aminopyridine. The fluorescent derivatives were separated by size-fractionation and reverse-phase HPLC, yielding 14 fractions. Structural analysis was accomplished by compositional and methylation analyses, by comparison of the HPLC elution patterns with reference oligosaccharides, by stepwise exoglycosidase digestions which were monitored by HPLC, and, where necessary, by 500-MHz 1H-NMR spectroscopy. Ten oligosaccharides consisted of mannose, N-acetylglucosamine and fucose alpha 1-6 and/or alpha 1-3 linked to the innermost N-acetylglucosamine. Four compounds, which comprised 10% of the oligosaccharide pool from phospholipase A2, contained a rarely found terminal element with N-acetylgalactosamine. The structures of the 14 N-glycans from honeybee phospholipase A2 can be arranged into the following three series: [formula: see text] PMID- 8504813 TI - Two-dimensional 1H-NMR study of the spatial structure of neurotoxin II from Naja naja oxiana. AB - The spatial structure of neurotoxin II from the venom of the central Asian cobra Naja naja oxiana was determined by two-dimensional 1H-NMR techniques and computational analysis. Nearly complete proton resonance assignments for 61 amino acid residues have been made using two-dimensional (2D) homonuclear total correlated spectroscopy, 2D homonuclear double-quantum-filtered correlated spectroscopy and 2D homonuclear NOE spectroscopy (NOESY) experiments. The cross peak volumes in NOESY spectra spin-spin coupling constants of vicinal protons NH C alpha H and C alpha H-C beta H and the observation of slow deuterium exchange of amide protons were used to define local structure and a set of constraints for distance geometry program DIANA. The average root-mean-square deviations are 53 pm for backbone heavy atoms and 118 pm for all heavy atoms of 19 final neurotoxin II conformations. The spatial structure is characterized by a short double stranded (residues 1-5 and 13-17) and a triple-stranded (residues 22-30, 33-41 and 50-54) antiparallel beta-sheets. PMID- 8504814 TI - Creatinase in its collapsed A state shows properties of a molten globule with dimeric quaternary structure. AB - In the past, the molten globule state at acidic pH (A state) has mainly been observed for small single-domain proteins. For more complex proteins such as immunoglobulin, alternatively folded states, with certain characteristics of the molten globule but different thermodynamic properties, were observed. In the present work, the acid-induced structural characteristics of a homodimer, creatinase from Pseudomonas putida, are described. The 91-kDa protein at pH 2 shows molten globule behavior in that there is (a) a high content of native-like secondary structure (monitored by far-ultraviolet circular dichroism), (b) changes in the solvent accessibility of intrinsic fluorophores (acrylamide quenching of protein fluorescence), (c) increased hydrophobic surface area (indicated by anomalous dye binding) and (d) a slight expansion of the hydrodynamic volume (calculated from S20,solv, obtained from analytical ultracentrifugation). The enzyme at pH 2 shows reversible cooperative transitions in guanidinium chloride or urea (at elevated ionic strength). Its quaternary structure remains unaltered, indicating that native-like subunit interactions are involved in the stabilization of the A state of the enzyme. Anions stabilize the compact conformation due to reduced intramolecular charge repulsion; for the same reason, the enzyme in its A state shows a strong tendency to aggregate at > 0.3 M NaCl. PMID- 8504815 TI - Photochemical cross-linking of the skeletal myosin head heavy chain to actin subdomain-1 at Arg95 and Arg28. AB - F-actin specifically substituted with the photocross-linker, p azidophenylglyoxal, at Arg95 and Arg28 was isolated and characterized. Upon complexation with myosin subfragment-1 (S1) and photolysis at 365 nm, it was readily cross-linked to the S1 heavy chain with a yield of about 13-25%, generating four major actin-heavy-chain adducts with molecular masses in the range 165-240 kDa. The elevated Mg(2+)-ATPase of the covalent complexes displayed a turnover rate of 33 +/- 8 s-1 which is similar to the values reported earlier for other acto-S1 conjugates. The cross-linking between various proteolytic S1 and actin derivatives, combined with the fluorescent and immunochemical detection of the photocross-linked products, indicated that the arylnitrene group on Arg95 was inserted predominantly in the central 50-kDa region, whereas that attached to Arg28 mediated the selective cross-linking of the COOH-terminal 22-21-kDa fragments of the heavy chain, most probably by reacting at or near the connector segment between the 50-kDa and 20-kDa fragments. The rapid photoactivation and cross-linking to S1 of the substituted F-actin, which can be accomplished on a millisecond time scale, may serve to probe the structural dynamics of the interaction of the S1 heavy chain with subdomain-1 of actin during the ATPase cycle. PMID- 8504816 TI - Structure of the O-specific polysaccharide containing pentitol phosphate, isolated from Hafnia alvei strain PCM 1191 lipopolysaccharide. AB - The O-specific polysaccharide of the lipopolysaccharide produced by Hafnia alvei strain PCM 1191 was shown by composition and methylation analyses, periodate oxidation and one- and two-dimensional 1H- and 31P-NMR spectroscopy to be a polymer of a branched hexasaccharide repeating units having the structure: [formula: see text] where LAraol = L-arabitol The polysaccharide of 1191 strain has teichoic-acid-like character. Its peculiar feature is the presence of arabitol phosphate, a component observed for the first time in bacterial lipopolysaccharides. PMID- 8504817 TI - Purification and characterisation of glyoxalase II from human red blood cells. AB - Glyoxalase II was purified from human red blood cells. The purification factor was 83,300 and the yield was 24% or 1.7 micrograms/ml red blood cells. The purified protein was a monomer with a molecular mass of 29,200 Da and an isoelectric point of 8.3. The rate of hydrolysis of S-D-lactoylglutathione to reduced glutathione and D-lactate, catalysed by glyoxalase II, followed Michaelis Menten kinetics where the Km and kcat values were 146 +/- 9 microM and 727 +/- 16 s-1, respectively in 50 mM Tris/HCl, pH 7.4 at 37 degrees C. Other S-2 hydroxyacylglutathione derivatives were also acceptable substrates. S-p Nitrobenzoxycarbonylglutathione was a potent competitive inhibitor of glyoxalase II with a Ki value of 1.20 +/- 0.21 microM, and the hemithioacetal formed non enzymically from the reaction of methylglyoxal with reduced glutathione was a weak competitive inhibitor with a Ki value of 834 +/- 98 microM. PMID- 8504818 TI - The interaction of daunomycin with model membranes. Effect of the lipid physical state and the lipid composition. AB - The sensitivity of the keto and carbonyl infrared bands of daunomycin (DNM) to hydrogen bonding with the solvent, has been used to study the effect of the physical state and lipid composition of the bilayer on drug location. Our results show that penetration of daunomycin into dihexadecylphosphatidylcholine (Hxd2GroPCho) or dipalmitoylphosphatidylcholine bilayers, is dependent on the molecular packing of the lipid. DNM incorporates into the bilayer once the interdigitation of the gel phase of Hxd2GroPCho has been removed, above the pretransition temperature. Melting of the hydrocarbon chains of both lipids, at the main transition temperature, allows a similar and deeper drug penetration into the bilayers. Experiments using liposomes with different lipid compositions suggest that the relative concentration of certain lipids may modulate the location of DNM within the bilayer. Cholesterol, in a concentration-dependent manner, inhibits incorporation of anthracycline into apolar regions of the bilayer, while the presence of the negatively charged lipid dihexadecylphosphatidic acid is able to prevent the inhibitory effect of the steroid, allowing deeper penetration of the drug. Due to the importance of drug membrane interactions in anthracycline cytotoxicity, the relevance of the observed differences in daunomycin location, caused by physical and/or chemical changes in the biological membranes, is discussed. PMID- 8504819 TI - Metabolic characteristics of rat liver cytosolic 5SRNA. AB - 5SRNA were purified from the cytosol, ribosomes, nucleoli and nucleoplasm of rat liver. The 5'-terminal and 3'-terminal sequences of these 5SRNA species were shown to be the same. The time course of changes in specific activities of these 5SRNA in rat liver, 20 min to 16 h after intraperitoneal injection of [14C]orotic acid, were investigated. The specific activity of cytosolic 5SRNA increased almost linearly for 3 h, without a lag, to a high value, then decreased rapidly. The specific activity of cytosolic 5SRNA was much higher than the specific activities of 5SRNA from the other cellular components over 45 min to 6 h after intraperitoneal injection, although at 20 min the specific activity was similar to that of nucleoplasmic 5SRNA. Thus, cytosolic 5SRNA of rat liver is characterized by a high rate of turnover, which was shown to be comparable to that of heterogeneous nuclear RNA. The specific activity of 5SRNA, 45 min to 6 h after intraperitoneal injection, was as follows; cytosolic > nucleoplasmic > nucleolar > ribosomal 5SRNA. The specific activity of nucleoplasmic RNA that migrated slightly slower than nucleoplasmic 5SRNA on PAGE was much higher than that of cytosolic 5SRNA or nucleoplasmic 5SRNA, and so may be the precursor of nucleoplasmic 5SRNA. Together, these results indicate that cytosolic 5SRNA is transferred from the nuclei to the cytosol immediately after maturation of the precursor of nucleoplasmic 5SRNA without entering the nucleoplasmic pool of 5SRNA. PMID- 8504820 TI - Gastric chief cell-specific transcription of the pepsinogen A gene. AB - The molecular mechanisms underlying the regulation of pepsinogen A (PGA) gene expression in mammalian cells are poorly understood. In this paper we describe the structural and functional analysis of the pepsinogen A gene promoter in the pig. By genomic Southern analyses we demonstrate that, in contrast with human PGA genes which are amplified and organized in haplotypes, only a single PGA gene is present per haploid porcine genome. With the aim of identifying promoter elements mediating the gastric mucosa cell-specific transcription of the PGA gene in pig, we isolated a PGA gene from a porcine genomic library. The nucleotide sequence of the first exon and 1.7 kb of the upstream DNA region were determined and compared with the corresponding regions of the human PGA gene encoding isozymogen Pg5. In order to study the promoter activity of the PGA gene a functional assay was developed: we succeeded in obtaining primary monolayer cultures of porcine gastric mucosal chief cells, suitable for transfection. Fragments of 5'-flanking and noncoding first exon sequences of the porcine and human PGA genes were linked to the chloramphenicol acetyltransferase (CAT) gene. The transcriptional activity of these hybrid genes was assessed in transient expression assays upon transfection (lipofection) of gastric and nongastric cells. Whereas PGA 5' flanking sequences showed no promoter activity in nongastric cell types, the DNA region from -205 to +21 was found to be sufficient to direct expression of the porcine PGA constructs in a cell-specific manner. Further deletion analysis of the proximal promoter fragment identified several regions (-205 to -167, -127 to 67 and +2 to +21) acting synergistically in the transcriptional regulation of the PGA gene. In contrast, all human PGA-CAT constructs used failed to show promoter activity in porcine gastric chief cells, indicating species-specific control of PGA gene expression. In addition, the transcriptional activity of the porcine PGA promoter in chief cells from pig was completely abolished by in vitro CpG methylation. Footprint analyses of the proximal promoter fragment using nuclear extracts from either porcine gastric mucosal chief cells or liver revealed some notable differences between both extracts, which might reflect the interaction with (a) cell-specific factor(s). PMID- 8504821 TI - Collagen II from articular cartilage and annulus fibrosus. Structural and functional implication of tissue specific posttranslational modifications of collagen molecules. AB - Collagen II was isolated and characterized from hyaline cartilage (articular cartilage) and fibro-cartilage (annulus fibrosus). Collagen II from the latter tissue has a substantially higher degree of hydroxylation and glycosylation than that isolated from articular cartilage. The higher degree of posttranslational modification was associated with a slower electrophoretic mobility, a greater resistance to mammalian collagenase digestion and a higher thermal stability. An increase of glycosylation accelerates the initial steps in fibril formation of collagen molecules but slows down the following lateral growth. The newly formed aggregates of collagen II from annulus fibrosus consisted of fibrils with a smaller diameter. PMID- 8504822 TI - Characterization of the high-affinity oligosaccharide-binding site of the 205-kDa porcine large granular lymphocyte lectin, a member of the leukocyte common antigen family. AB - Membrane lectins of mammalian large granular lymphocytes are thought to be important receptors in their non-major-histocompatibility complex-restricted activation. A triantennary desialylated oligosaccharide has been reported as the most effective triggering structure [Pospisil M., Kubrycht J., Bezouska K., Taborsky O., Novak M. & Kocourek J. (1986) Immunol. Lett. 12, 83-90] while its cell surface receptor has recently been identified in pig natural killer cells as a 205-kDa membrane lectin resembling the proteins of the leukocyte common antigen family (LCA). In this study we have prepared 4-azidophenyl (photoactivatable) and 4-hydroxyphenyl (radio-iodinatable) derivatives of triantennary oligosaccharides by a new procedure which allows the natural conformation of the N-glycosidic linkage between the oligosaccharide and the respective labeling group to be retained. We used these high-affinity ligands to investigate the oligosaccharide combining site of the 205-kDa lectin. Photoaffinity labeling of the whole cells and solubilized proteins confirmed that a 205-kDa polypeptide constitutes the major cell-surface calcium-independent receptor for triantennary oligosaccharides in pig lymphocytes. Isolation and manual sequencing of two ligand-labeled and eleven other peptides proved that the 205-kDa lectin represents a member of the LCA family expressing exons 4 and 6 during alternative splicing and that the high affinity binding site is localized in the N-terminal 70-kDa extracellular domain. Binding studies with radiolabeled oligosaccharides and the above carbohydrate recognition domain subjected to various chemical and enzymatic treatments indicated that the binding of oligosaccharides might be significantly modulated by sialylated O-glycosidically linked lineage-specific carbohydrate epitopes localized within this domain. Affinity chromatography of LCA isolated by conventional methods on immobilized oligosaccharides revealed that only a fraction of these cell-surface glycoproteins expressed high-affinity binding sites for the oligosaccharide ligands. Thus, N-linked oligosaccharide moieties of cell-surface glycoproteins seem to represent possible ligands of LCA that may be important in intercellular adhesion and oligosaccharide-mediated activation of lymphocytes. PMID- 8504823 TI - Purification and biochemical characterization of the hydantoin hydrolyzing enzyme from Agrobacterium species. A hydantoinase with no 5,6-dihydropyrimidine amidohydrolase activity. AB - A soluble hydantoinase (5,6-dihydropyrimidine amidohydrolase) was purified to homogeneity from a newly isolated Agrobacterium species. This hydrolase consists of about 578 aminoacyl residues and is a slightly acidic protein with an isoelectric point of 6.5. The first 22 N-terminal amino acid residues were determined by Edman degradation. Determination of the relative molecular mass of the protein by gel-filtration chromatography gave an apparent value of 250,000. The subunit M(r) was 62,000, as estimated by analytical SDS/PAGE and 66,500, as estimated by denaturing gel-filtration chromatography. The pure hydantoinase exhibits the following hydrodynamic properties: a sedimentation coefficient of 8.8 S as determined by sedimentation velocity experiments; a Stokes radius of 6.8 nm; a diffusion coefficient of 31.5 microns2.s-1 as determined by analytical gel filtration chromatography. From these experimental data, the following physical constants could be calculated: a theoretical M(r) of 265,000, a frictional ratio, f/fo, of 1.59, a maximal axial ratio, a/b, of 3.1; a Perrin shape factor, F, of 1.37. As shown by different Km values, the preferred substrates of this hydrolase were 5-monosubstituted hydantoins bearing aromatic substituents. 5,5 Dimethylhydantoin and different thio analogs of the 5-p-hydroxyphenylhydantoin molecule are competitive inhibitors of this hydrolase. The classification of this microbial hydantoinase, which exhibits no hydrolytic activity with all the dihydropyrimidines tested, under the systematic name of 5,6-dihydropyrimidine amidohydrolase, and its putative metabolic role are further discussed. PMID- 8504824 TI - Flux partitioning in the split pathway of lysine synthesis in Corynebacterium glutamicum. Quantification by 13C- and 1H-NMR spectroscopy. AB - The Gram-positive Corynebacterium glutamicum has the potential to synthesize L lysine via a split pathway, where amino-ketopimelate is converted to the ultimate lysine precursor diaminopimelate either by reactions involving succinylated intermediates, or by one single reaction catalysed by D-diaminopimelate dehydrogenase. To quantify the flux distribution via both pathways, 13C-enriched glucose was used and specific enrichments in lysine and in pyruvate-derived metabolites were determined by 13C- and 1H-NMR spectroscopy. Using a system of linear equations, the contribution of the D-diaminopimelate dehydrogenase pathway was determined to be about 30% for the total lysine synthesized. This was irrespective of whether lysine-accumulating mutants or the wild-type strain were analysed. However, when the distribution was determined at various cultivation times, the flux partitioning over the dehydrogenase pathway in a producing strain decreased from 72% at the beginning to 0% at the end of lysine accumulation. When ammonium sulphate was replaced by the organic nitrogen source glutamate, the ammonium-dependent D-diaminopimelate dehydrogenase pathway did not contribute to total lysine synthesis at all. Additional experiments with varying initial ammonium concentrations showed that in Corynebacterium glutamicum the flux distribution over the two pathways of lysine synthesis is governed by the ammonium availability. This is thus an example where an anabolic pathway is directly influenced by an extracellular medium component, probably via the kinetic characteristics of D-diaminopimelate dehydrogenase. PMID- 8504825 TI - Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes. AB - Metformin (dimethylbiguanide) has been used for more than 30 years as an antihyperglycemic agent in the treatment of diabetes mellitus, but its effect on gluconeogenesis is still controversial. In isolated hepatocytes from fasted rats, a significant inhibition of glucose production from lactate/pyruvate (10:1, mol/mol), fructose, alanine or glutamine, following metformin addition, is observed. Moreover, in hepatocytes perifused with dihydroxyacetone as the gluconeogenic substrate and treated with 0.5 mM metformin, an inhibition of the glucose flux and a simultaneous stimulation of the lactate/pyruvate flux were observed. This enhancement of lactate/pyruvate formation appears to be due to an effect on the pyruvate-kinase enzyme. A direct effect of metformin on pyruvate kinase cannot explain this result, since pyruvate-kinase activity was not affected by metformin at this concentration. In contrast, the addition of metformin caused a significant decrease in the cellular ATP concentration, a known allosteric inhibitor of this enzyme. This could explain the stimulation of pyruvate-kinase activity following metformin addition and thus the inhibition of gluconeogenesis. PMID- 8504826 TI - Expression of the Xenopus D2 dopamine receptor. Tissue-specific regulation and two transcriptionally active genes but no evidence for alternative splicing. AB - In the amphibian Xenopus laevis the D2 dopamine receptor is involved in the regulation of the melanotrope cells of the intermediate pituitary during background adaptation of the animal. The Xenopus D2 receptor has been found to be pharmacologically different from the mammalian D2 receptor. In a number of mammalian species alternative splicing generates two molecular forms of the D2 receptor. These isoforms differ by the presence or absence of 29 amino acids in the third cytoplasmic loop which is thought to be involved in guanine-nucleotide binding-regulatory-protein (G-protein) binding of the receptor. We previously described a cDNA encoding the large isoform of the Xenopus D2 receptor. Here we report on the isolation of a brain cDNA encoding a second, structurally different Xenopus D2 dopamine receptor. Both Xenopus receptors correspond to the large isoform of the D2 receptor and they display a high degree of sequence identity with their mammalian counterparts. Their occurrence reflects the expression of two Xenopus D2 receptor genes and they are expressed to approximately the same level. In contrast to mammals, PCR analysis gave no evidence for alternative splicing during D2 receptor expression in Xenopus brain and pituitary. Tissue specific expression of the Xenopus D2 receptor was observed in the pituitary during background adaptation. The low level of receptor mRNA in melanotrope cells of white animals compared to that of black animals may be caused by chronic dopamine stimulation of melanotrope cells in white animals with consequent cellular desensitization and down regulation of the D2 receptor gene. PMID- 8504827 TI - A novel very small subunit of a selenium containing [NiFe] hydrogenase of Methanococcus voltae is postranslationally processed by cleavage at a defined position. AB - A coenzyme-F420 non-reducing [NiFe] hydrogenase was isolated from Methanococcus voltae. It consists of three subunits. They are the products of the previously identified genes vhuA, vhuG and vhuU. The vhuU gene product is of only 25 amino acids. This novel very small hydrogenase subunit contains selenocysteine within a conserved amino-acid sequence previously shown to be involved in Ni coordination. The subunit is shorter than the predicted primary gene product and is therefore apparently post-translationally processed. PMID- 8504828 TI - Determination of the nuclear-magnetic-resonance solution structure of cardiotoxin CTX IIb from Naja mossambica mossambica. AB - The NMR structure of cardiotoxin CTX IIb from Naja mossambica mossambica in aqueous solution was determined from a total of 593 nuclear Overhauser enhancement distance constraints and 135 dihedral angle constraints, which were collected using two-dimensional homonuclear 1H-NMR experiments. Structure calculations were performed with the program DIANA, using the redundant dihedral angle constraints strategy for improved convergence, followed by restrained energy minimization with the program FANTOM and a modified version of the program AMBER. The CTX IIb structure is represented by a group of 20 conformers with an average root-mean-square deviation relative to the mean solution structure of 0.072 nm for the backbone atoms, and 0.116 nm for all heavy atoms. The molecular structure of CTX IIb is characterized by a three-stranded beta-sheet made up of residues 20-26, 32-39 and 48-54, and a two-stranded beta-sheet composed of residues 1-5 and 10-14. A cluster of four disulfide bonds, 3-21, 14-38, 42-53 and 54-59, form the core of the molecule and crosslink the individual polypeptide strands. The NMR structure is similar to the previously reported X-ray crystal structure of the cardiotoxin CTX VII4 from the same species. Differences between the two structures were noted in the tips of the two loops formed by residues 6-9 and 27-31, which connect the beta-strand 1-5 with 10-14, and 20-26 with 32-39, respectively. For these loops the NMR data also indicate significantly increased dynamic disorder in the solution structure. These observations are discussed with respect to earlier suggestions by others that these two loops are essential structural elements for function and specificity of a wide variety of homologous toxins. PMID- 8504829 TI - Isolation and characterization of a cDNA clone encoding a Pleurodeles lectin. AB - A cDNA encoding a lectin secreted by the oviduct of Pleurodeles waltl has been isolated and sequenced. The cDNA was identified by comparing the N-terminal amino acid sequence of the purified P. waltl lectin polypeptides with the amino-acid sequence deduced from the cDNA. The two chains of the mature protein can be encoded within a unique mRNA. Two mRNA were also found in the oviduct extracts. However, they probably result from differential polyadenylation events. The mRNA are strictly localized in the anterior part of the oviduct and increase after estradiol stimulation, two characteristics which have been previously demonstrated for the protein. P. waltl is known to possess a very high DNA content (approximately 2 x 10(10) bp) but the aforementioned results and Southern blot experiments suggest a unique or at least a very low gene-copy number for this protein. The amino-acid sequence of the P. waltl lectin deduced from the cDNA sequence shows similarities with the C-type carbohydrate-recognition domains of animal lectins as defined by Drickamer [Drickamer, K. (1988) J. Biol. Chem. 263, 9557-9560]. Although it is regulated by estradiol, the P. waltl lectin amino acid sequence shows a higher similarity with animal lectins involved in the defence of the organism than with those involved in reproduction and development. PMID- 8504830 TI - Molecular basis for heme-dependent induction of heme oxygenase in primary cultures of chick embryo hepatocytes. Demonstration of acquired refractoriness to heme. AB - The effects of heme on the induction of mRNA and protein synthesis for heme oxygenase-1 have been studied in primary cultures of chick embryo liver cells. Heme increased the amount of mRNA and the rate of heme oxygenase-1-gene transcription in a dose-dependent fashion, with a maximal 20-fold increase occurring at 20 microM heme. The largest increase in the rate of transcription, measured by nuclear run-on assays, occurred at 5 h, 2 h earlier than the maximum increase in the amount of mRNA, measured by densitometry of Northern blots. 7-15 h after heme addition, the half-life of heme-oxygenase-1 mRNA was 3.5 h in the presence or absence of actinomycin D. In contrast, addition of cycloheximide markedly increased the stability of the message (half-life = 18 h), suggesting that a short-lived protein plays a key role in modulating heme oxygenase-1 mRNA levels. The half-life of heme-induced heme-oxygenase-1 protein, measured by [35S]methionine labelling and immunoprecipitation, was 15 h. This long half-life of the protein can largely account for the additional finding that, following addition of heme, the amount of enzyme protein in the cells increased for 10 h, after which it remained essentially constant for 15 h. A striking finding was that, after an initial burst of heme-stimulated gene transcription, the cells became refractory to further heme-mediated induction. This acquired resistance could not be attributed to the following: a longer duration of culture time; cellular toxicity caused by heme; a lack of heme in the medium or the cells; secretion of heme-binding proteins into the medium, preventing further heme uptake; the induction of cellular heme catabolism sufficient to deplete cellular heme. Instead, the results suggest a down-regulation of the intracellular machinery required for heme-dependent induction of heme oxygenase-1. PMID- 8504831 TI - Translational repression of EF-1 alpha mRNA in vitro. AB - In this report we show that when 10,000 x g supernatant extracts of growth arrested murine erythroleukemia (MEL) cells are incubated there is a rapid conversion of essentially all mRNAs to non-translating messenger ribonucleoprotein (RNP) particles. Most of these RNPs are readily translated in an initiation-dependent manner when added to a nuclease-treated rabbit reticulocyte lysate. A notable exception is the RNP containing eucaryotic elongation factor 1 alpha (EF-1 alpha) mRNA. The mRNA for poly(A)-binding protein behaved similarly to EF-1 alpha. Previous work has demonstrated that the translation of both these mRNAs are repressed in vivo when the growth of a number of different mammalian cells is arrested [Slobin L. I. and Jordan, P. (1984) Eur J. Biochem. 145, 1984; Thomas, G. and Thomas, G. (1986) J. Cell Biol. 103, 1986]. Translational activity of EF-1 alpha mRNA could be restored by treating RNP particles with 0.5 M KCl, provided that the RNPs were separated from salt wash by chromatography on oligo(dT)-cellulose. Addition of the salt wash to total MEL cell mRNA significantly and selectively inhibited EF-1 alpha mRNA translation, suggesting that a component of the salt wash acts as a trans-acting translational repressor of EF-1 alpha mRNA. PMID- 8504832 TI - Conformational characterization by circular-dichroism spectroscopy of various fragments and analogs of calcitonin-gene-related peptide. AB - A conformational study by circular-dichroism spectroscopy of calcitonin-gene related peptide (CGRP) and related fragments and analogs was carried out in structure-promoting solvent mixtures. The structural characterization of rat CGRP alpha and the two isoforms of human CGRP, alpha and beta, revealed that these peptides possess very similar conformational features. The far-ultraviolet circular-dichroism spectra, in pure water, of human CGRP alpha, (hCGRP alpha), [Acm-Cys2,7]hCGRP alpha, various fragments and analogs indicated that these peptides exhibited predominantly a random-coil conformation. The addition of increasing concentrations of 1,1,1,3,3,3-hexafluoro-2-propanol to the peptide solutions resulted in a transition from a random-coil conformation to a stabilized alpha-helical structure. The substantial loss of helical content measured with [Acm-Cys2,7]hCGRP alpha, [Acm-Cys2,7]hCGRP-(1-24)-CONH2 and hCGRP (8-37), compared to hCGRP alpha, suggested that the N-terminal disulfide bridge of hCGRP alpha is essential for adopting a highly stabilized alpha-helical conformation. Moreover, the lower helical content of hCGRP-(8-37), as compared to [Acm-Cys2,7]hCGRP alpha, as well as spectroscopic results measured with various fragments and analogs of hCGRP-(8-37) revealed that N-terminal residues found in the peptide segment 1-12 are important for the full conservation of the amphiphilic alpha-helix. In addition, the similar alpha-helical content of hCGRP (8-37) and hCGRP-(8-18) indicated that the C-terminal segment 19-37 is not essential for the stabilization of the alpha-helix structure. PMID- 8504833 TI - Structure/activity relationship of adenine-modified NAD derivatives with respect to porcine heart lactate dehydrogenase isozyme H4 simulated with molecular mechanics. AB - Using a significantly simplified modification procedure, four charged analogues of the coenzyme NAD, N(1)- and N6-(2-hydroxy-3-trimethylammoniumpropyl)-NAD, N(1) and N6-(3-sulfopropyl)-NAD were prepared. The kinetic parameters of these derivatives and N(1)-(2-aminoethyl)-NAD, N6-(2-aminoethyl)-NAD and tricyclic 1,N6 ethanoadenine-NAD, all with alterations to the adenine moiety, were determined for porcine heart lactate dehydrogenase isoenzyme H4. The coenzyme activity depends on both position and charge of the introduced groups. Modification of the N6-position leads to a 25-250-fold increase of the kcat/Km value compared to the related N(1) derivative. The kcat/Km value for 1,N6-ethanoadenine-NAD is in the range between that of N(1)-(2-aminoethyl)-NAD and N6-(2-aminoethyl)-NAD. In the case of both N(1) and N6 functionalization, the Km values increase from (3 sulfopropyl)-NAD, with a negatively charged substituent at the adenine, over (2 amino-ethyl)-NAD to (2-hydroxy-3-trimethylammoniumpropyl)-NAD with an uncharged and positively charged substituent, respectively, at the adenine. All N6 derivatives are analogues like NAD with respect to Km and/or Vmax and kcat/Km. The conformation of NAD and its derivatives was calculated and their interaction in the active site of lactate dehydrogenase was simulated using the molecular mechanics program AMBER. The significant differences in activity in correlation to porcine heart lactate dehydrogenase isoenzyme H4 could be rationalized by modelling the three-dimensional structure of the NAD site. PMID- 8504834 TI - On the activation mechanism of the H(+)-ATP synthase and unusual thermodynamic properties in the alkalophilic cyanobacterium Spirulina platensis. AB - The activation requirements and thermodynamic characteristics of ATP synthase from the alkalophilic cyanobacterium Spirulina platensis were studied in coupled membrane vesicles. Activation by methanol increased the Vmax, while the Km for MgATP was unaffected (0.7 mM). We propose that in Sp. platensis, as in chloroplasts, the activating effect of methanol is based on perturbation of the gamma-epsilon subunit interaction. Light-driven ATP synthesis by membrane vesicles of Sp. platensis was stimulated by dithiothreitol. The characteristics of the activation of the ATP synthase by the proton electrochemical potential difference (delta mu H+) were analyzed on the basis of the uncoupled rates of ATP hydrolysis as a function of a previously applied proton gradient. Two values of delta mu H+, at which 50% of the enzyme is active, were found; 13-14 kJ.mol-1 for untreated membrane vesicles, and 4-8 kJ.mol-1 for light-treated and dithiothreitol-treated membrane vesicles. These values are lower than the corresponding values for the oxidized and reduced forms, respectively, of the chloroplast enzyme. Although no bulk proton gradient could be observed, membrane vesicles of Sp. platensis were able to maintain an equilibrium phosphate potential (delta Gp) of 40-43.5 kJ.mol-1, comparable to values found for Synechococcus 6716 and Anabaena 7120 membrane vesicles. Acid/base-transition experiments showed that the thermodynamic threshold, delta mu H+, for ATP synthesis, catalyzed by light-treated and dithiothreitol-treated Spirulina membrane vesicles, was less than 5 kJ.mol-1. The activation characteristics and the low thermodynamic threshold allow ATP synthesis to occur at low delta mu H+ values. The findings are discussed, both with respect to differences and similarities with the enzymes from chloroplasts and other cyanobacteria, and with respect to the alkalophilic properties of Sp. platensis. PMID- 8504835 TI - Isomeric sn-1-octadecenyl and sn-2-octadecenyl analogues of lysophosphatidylcholine as substrates for acylation and desaturation by plant microsomal membranes. AB - To provide supporting and independent evidence for lipid-linked desaturation of acyl groups in plant microsomal membranes, ether-analogous substrates were synthesized and used for in-vitro desaturation studies. The substrates included 1 O-(9-cis-octadecenyl)-sn-glycero-3-phosphocholine and 2-O-(9-cis-octadecenyl)-sn glycero-3-phosphocholine as well as labelled 1-O-(9-cis-[9,10-3H2]octadecenyl)-sn glycero-3-phosphocholine. In experiments with microsomal membranes from developing fruits of sunflower, it was shown that both isomeric alkenyl ether phospholipids were acylated with [14C]oleoyl-CoA and [14C]palmitoyl-CoA. In the presence of O2 and NADH, the oleoyl groups incorporated into both compounds, i.e. at the sn-1 and sn-2 positions of the glycerol backbone of the substrate, were desaturated to linoleoyl residues in similar proportions. Under the same conditions, an additional double bond, but not an enol-ether double bond, was introduced into the ether-linked side chain of acylated 1-O-(9-cis-[9,10 3H2]octadecenyl)-sn-glycero-3-phosphocholine. This represents the first demonstration of this type of desaturation with an alkenyl ether phospholipid and confirms previous conclusions that plants introduce second and further double bonds into lipid-linked acyl groups. PMID- 8504836 TI - Functional coupling between sarcoplasmic-reticulum-bound creatine kinase and Ca(2+)-ATPase. AB - We investigated the role of creatine kinase bound to sarcoplasmic reticulum membranes of fast skeletal muscle in the local regeneration of ATP and the possible physiological significance of this regeneration for calcium pump function. Our results indicate that ADP produced by sarcoplasmic reticulum Ca(2+) ATPase is effectively phosphorylated by creatine kinase in the presence of creatine phosphate. This phosphorylation is an important function of the membrane bound creatine kinase because accumulation of ADP has a depressive effect on Ca(2+)-uptake by sarcoplasmic reticulum vesicles. The concentration-dependent depression of Ca(2+)-uptake by ADP was especially pronounced when there was strong back inhibition by high intravesicular [Ca2+]. ATP regenerated by endogenous creatine kinase was not in free equilibrium with the ATP in the surrounding medium, but was used preferentially by Ca(2+)-ATPase for Ca(2+) uptake. Efficient translocation of ATP from creatine kinase to Ca(2+)-ATPase, despite the presence of an ATP trap in the surrounding medium, can be explained by close localization of creatine kinase and Ca(2+)-ATPase on the sarcoplasmic reticulum membranes. These results suggest the existence of functional coupling between creatine kinase and Ca(2+)-ATPase on skeletal muscle sarcoplasmic reticulum membranes. Several factors (amount of membrane-bound creatine kinase, oxidation of SH groups of creatine kinase, decrease in [phosphocreatine]) can influence the ability of creatine kinase/phosphocreatine system to support a low ADP/ATP ratio and fuel the Ca(2+)-pump with ATP. These factors may become operative in the living cells, influencing functional coupling between creatine kinase and Ca(2+)-ATPase and may have an indirect effect on Ca(2+)-pump function before Ca(2+)-ATPase itself is affected. PMID- 8504837 TI - Acetyl-acyl carrier protein is not a major intermediate in fatty acid biosynthesis in spinach. AB - The extent to which acetyl-acyl carrier protein (acetyl-ACP) is an intermediate in fatty acid biosynthesis was examined. Acetyl-ACP was the least effective primer of fatty acid synthesis by spinach extracts when compared to acetyl-CoA, butyryl-ACP or hexanoyl-ACP. Furthermore, the rate of acetyl-ACP-primed fatty acid synthesis was inhibited significantly by cerulenin, indicating that the slow utilization of acetyl-ACP was predominantly by 3-oxoacyl-ACP synthase I. In light incubated isolated chloroplasts with high rates of fatty acid synthesis (greater than 800 nmol.h-1.mg chlorophyll-1), the rate of acetyl-ACP metabolism was at least 10-30-fold slower than the rate of butyryl-ACP metabolism. The relatively slow metabolism of acetyl-ACP provided in situ evidence that (a) butyryl-ACP was formed principally from condensation of malonyl-ACP with acetyl-CoA and (b) acetyl-ACP was a minor participant in fatty acid biosynthesis. PMID- 8504838 TI - FAD and substrate analogs as probes for lysine N6-hydroxylase from Escherichia coli EN 222. AB - Lysine N6-hydroxylase catalyzes the hydroxylation of the N-terminal amino function of L-lysine at the expense of NADPH and molecular oxygen. The enzyme also requires FAD for its catalytic activity. Unlike other flavoprotein monooxygenases, binding of FAD is rather weak with a Kd of 30 microM at 4 degrees C. The spectral properties of FAD bound to lysine N6-hydroxylase are very similar to free oxidized FAD. In the absence of substrate, the enzyme has an NADPH oxidase activity which results in the generation of hydrogen peroxide. With increasing concentration of L-lysine, the NADPH oxidase activity is enhanced up to 10-fold and the generation of hydrogen peroxide decreases. At the same time, the substrate is hydroxylated. Km values for L-lysine and FAD were determined as 105 microM and 0.7 microM, respectively. Utilizing FAD analogs, we could demonstrate that L-lysine exerts its effector role mostly on the reductive half reaction of the overall catalytic cycle. Prolonged incubation of the enzyme with either 8-chloro- or 8-fluoro-FAD gave rise to a covalently attached flavin which is formed as a result of the nucleophilic attack of a thiolate on the 8-position of the flavin. Several lines of evidence indicate that the reaction takes place in the FAD binding site of the protein. The substrate specificity was investigated using amino acids with various lengths of side chain. L-Lysine and derivatives with similar side chain length are hydroxylated by lysine N6 hydroxylase. Ornithine, the lower homolog of lysine, was not hydroxylated and did not affect the NADPH oxidase activity of the enzyme. On the other hand, homolysine accelerated the rate of NADPH oxidation but was not hydroxylated. Additional requirements for efficient hydroxylation were also investigated using a variety of substrate analogs. From these studies a schematic structure of the active site of the enzyme was deduced. Sequence comparison of the FAD binding site of various flavoproteins revealed possible factors for weak binding of the cofactor in the case of lysine N6-hydroxylase. PMID- 8504839 TI - Stable isotopic tracers as metabolic probes in exercise. PMID- 8504840 TI - Physiological limiting factors and distance running: influence of gender and age on record performances. PMID- 8504841 TI - Sport and socialization. PMID- 8504842 TI - Orthostasis: exercise and exercise training. AB - There are two major problems here that are not independent. One is the more practically oriented problem of determining the effect of various modes of exercise training on gravitational tolerances, i.e., the point of syncope (unconsciousness) usually estimated from the time of appearance of presyncopal signs and symptoms. The other is more theoretical and concerns the mechanism of blood pressure failure that results in syncope. In many experimental designs these two problems or purposes have been intermingled, with equivocal results. PMID- 8504843 TI - Thermoregulation in women. PMID- 8504844 TI - Skeletal muscle regeneration and plasticity of grafts. AB - The sequence of molecular and cellular events of muscle ontogeny leads to the proliferation, fusion, and differentiation of myoblasts to muscle cells. This sequence is closely paralleled in the grafting-ischemia model in which adult myoblast-satellite cells function as the muscle precursor cells. The study of skeletal muscle regeneration is a fertile and promising area of research in myogenesis. The early regenerative development and maturation of muscle is similar regardless of the perturbation that induced the degeneration-regeneration sequelae. In light of this, we maintain that the skeletal muscle graft model is useful to rigorously evaluate many regulatory aspects of skeletal muscle development and maturation in an adult animal host. One advantage of the graft model is that manipulation of the adult host, such as with exercise or hormone treatment, allows insight into their regulatory roles in muscle development and maturation. These approaches are often not possible for developing skeletal muscle in utero or in ovo. After skeletal muscle grafting, many structural and functional characteristics change with time until they reach a stable value. Successful regeneration requires revascularization, cellular infiltration, phagocytosis of necrotic muscle fibers, proliferation and fusion of muscle precursor cells, reinnervation, and recruitment and loading. The time taken to reach stable values varies among different structural and functional variables, and many reach stable values that are less than those of control skeletal muscle. There are differences in the degree of regenerative success because of the size of muscle mass grafted. In small and large grafts, regeneration is enhanced by facilitation of the reinnervation. Regeneration is evident without vascular repair in grafts of up to approximately 6 g, although in all but the 100 to 150 mg grafts in rats, a significant necrotic core is present. Regeneration is typically unsuccessful when muscle masses greater than 6 g are grafted without vascular repair. Large muscles can be grafted with vascular repair, and in this case, the cellular response is quite different, as the majority of fibers survive rather than degenerate and regenerate. Changing the components of physical activity during skeletal muscle regeneration can alter several attributes of the graft phenotype. The consensus of several experiments supports the interpretation that proper recruitment and force development by grafts are essential variables in the regulation of the development and maturation of muscle grafts. Morphological and physiological attributes of grafts adapt to changes in the habitual level of physical activity in a qualitatively similar fashion to control muscle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504845 TI - Fluid replacement during exercise. AB - Current evidence indicates that adequate fluid ingestion during exercise enhances athletic performance, prevents a fall in plasma volume, stroke volume, cardiac output and skin blood flow, maintains serum sodium concentrations and serum osmolality, lowers rectal temperature and the perception of effort, and prevents a progressive rise in heart rate. Rates of sweating and urine flow are not influenced by fluid ingestion. The evidence suggests that the maintenance of serum osmolality and serum sodium concentrations at pre-exercise levels is the important determinant of these beneficial effects of fluid ingestion on cardiovascular function and thermoregulation. The provision of glucose in the ingested solution may be necessary to optimize performance; glucose ingestion that enhances fluid and sodium absorption in the small bowel may also present a progressive rise in oxygen consumption during exercise. Sweetened carbohydrate containing drinks may also increase fluid intake during exercise, thereby minimizing voluntary dehydration. Hence, the optimum solution for ingestion during exercise should provide carbohydrate, probably at rates of about 1 g/min and electrolytes in concentrations that, when drunk at the optimum rate, maintain serum osmolality and plasma volume at pre-exercise levels by replacing exactly that water and electrolyte losses from the extracellular space. At present, the composition of the fluid that will optimize electrolyte and fluid replacement of the extracellular space is not established. Neither are the optimum rates of fluid ingestion during exercise known. At low sweat rates (< 1 liter/hr), it is probable that all of the lost fluid can and should be replaced; rates of fluid ingestion needed to offset higher sweat rates may exceed the maximum intestinal absorptive capacity for water. Furthermore, high rates of fluid intake (> 1 liter/hr) are achieved with difficulty during exercise, especially when running, and are likely to lead to feelings of abdominal discomfort, possibly due to the accumulation of unabsorbed fluid in the small bowel or colon. Practicing to drink regularly during training might reduce the severity and frequency of these symptoms, possibly by increasing intestinal absorptive capacity. Most athletes are "reluctant" drinkers during exercise and do not ingest fluid at rates equal to their rates of fluid loss; hence, they develop progressive (voluntary) dehydration during prolonged exercise. Surprisingly, the level of voluntary dehydration that develops during exercise is relatively independent of the duration or intensity of the activity. The factors that explain these phenomena remain elusive. Fluid consumption during exercise is enhanced by the ingestion of cold, sweet fluids. Simultaneous food consumption also stimulates fluid ingestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504846 TI - Biology and mechanics of ligament and ligament healing. PMID- 8504847 TI - Plasticity of muscle fiber and motor unit types. PMID- 8504848 TI - Exercise and weight control. AB - Several important questions need to be answered to increase the likelihood that exercise will be accepted by the millions in the population who are obese. What is the minimum exercise "dose" (intensity, duration, frequency) and what is the optimal mode to bring about substantial fat weight loss, with minimal loss of lean mass? What is the best nutritional plan to optimize fat utilization during exercise, without impairing performance or loss of lean mass? Which diet and exercise programs maximally increase utilization of centrally deposited fat and how can hyperplastic obesity best be treated? Also of interest is the potential role of resistance exercise for weight loss, and the predictors of weight loss success. For instance, do individuals with gynoid obesity really differ from individuals with android obesity in their utilization and loss of body fat during exercise? The potential advantages of exercise include: stimulation of fat as opposed to carbohydrate oxidation; increased energy use during the exercise itself and in the postexercise period; protection of lean body mass; possible reversal of the diet-induced suppression of BMR; and other health benefits. Among other parameters, the effectiveness of exercise on weight loss may be influenced by the type, intensity, frequency, and duration of exercise bouts and the duration of the training program, the nature of the excess fat stores, i.e., whether the person has obesity characterized by hyperplastic or hypertrophic adipose tissue or central (with large-intra-abdominal depot) or peripheral obesity, the composition and caloric content of the diet, and behavioral aspects that affect adherence to the program. With respect to this latter concern, even if a person has been very successful at weight loss in a metabolic ward or intensive program, he/she must eventually return to the outside world and figure out for himself/herself how to eat real food and/or maintain an activity level that promotes weight maintenance. Because diet and exercise habits are difficult to assess and to quantify in free-living populations, it continues to be difficult to evaluate the success of diet and/or exercise prescriptions for weight loss accurately and we continue to be plagued with questions regarding the effectiveness vs. efficacy of exercise as a means to control body weight. It would seem that the wide range of health benefits derived from regular exercise would justify emphasizing increased activity for inactive people, particularly for obese, sedentary individuals, whether or not ideal body weight or significant weight loss is achieved. PMID- 8504849 TI - Motor cortex and visuomotor behavior. PMID- 8504850 TI - Changes in skeletal muscle with aging: effects of exercise training. AB - There is an approximate 30% decline in muscle strength and a 40% reduction in muscle area between the second and seventh decades of life. Thus, the loss of muscle mass with aging appears to be the major factor in the age-related loss of muscle strength. The loss of muscle mass is partially due to a significant decline in the numbers of both Type I and Type II muscle fibers plus a decrease in the size of the muscle cells, with the Type II fibers showing a preferential atrophy. There appears to be no loss of glycolytic capacity in senescent skeletal muscle whereas muscle oxidative enzyme activity and muscle capillarization decrease by about 25%. Vigorous endurance exercise training in older people, where the stimulus is progressively increased, elicits a proliferation of muscle capillaries, an increase in oxidative enzyme activity, and a significant improvement in VO2max. Likewise, progressive resistive training in older individuals results in muscle hypertrophy and increased strength, if the training stimulus is of a sufficient intensity and duration. Since older individuals adapt to resistive and endurance exercise training in a similar fashion to young people, the decline in the muscle's metabolic and force-producing capacity can no longer be considered as an inevitable consequence of the aging process. Rather, the adaptations in aging skeletal muscle to exercise training may prevent sarcopenia, enhance the ease of carrying out the activities of daily living, and exert a beneficial effect on such age-associated diseases as Type II diabetes, coronary artery disease, hypertension, osteoporosis, and obesity. PMID- 8504851 TI - A novel human tyrosine kinase gene inducible in T cells by interleukin 2. AB - We have cloned a novel human protein tyrosine kinase gene specific to T cells by the polymerase chain reaction method. This gene encodes a 620 amino-acid polypeptide including a catalytic domain for tyrosine kinase, an SH2 domain and an SH3 domain, seemingly belonging to the src family. However, characteristics of a long unique N-terminal stretch and lack of a myristylation site at the N terminus and of a kinase regulatory tyrosine residue in the C-terminus classify this molecule into a new subfamily comprising recently cloned mouse tec, itk/tsk and human atk/bpk genes. This gene was transcriptionally induced in normal T cells by interleukin 2 stimulation. These results suggest the crucial roles of this gene in T cell proliferation and differentiation. PMID- 8504852 TI - The glucose transporter of Escherichia coli. Purification and characterization by Ni+ chelate affinity chromatography of the IIBCGlc subunit. AB - The IIBCGlc transmembrane subunit of the glucose transporter of E. coli containing a carboxy-terminal affinity tag consisting of six adjacent histidines was purified by nickel chelate affinity chromatography. The protein was constitutively overexpressed from a high copy number plasmid. 1.5 mg of 95% pure protein was obtained from 5 g (wet weight) cells. 70% of the phosphotransferase activity present in cell membranes was recovered. Adsorption to the nickel resin allows delipidation as well as rapid detergent exchange. The procedure was used to demonstrate exchange of subunits in the IIBCGlc dimer and it holds promise for the investigation of other protein-protein interactions. PMID- 8504853 TI - Phosphatidylglycerol dependent protein translocation across the Escherichia coli inner membrane is inhibited by the anti-cancer drug doxorubicin. Evidence for an electrostatic interaction between the signal sequence and phosphatidylglycerol. AB - OmpF-Lpp, a model secretory protein, requires both a positively charged signal sequence and phosphatidylglycerol (PG) for efficient translocation across the E. coli inner membrane. Modification of the signal sequence can, however, remove both these prerequisites for translocation providing OmpF-Lpp mutants which undergo either PG and charge dependent or PG and charge independent translocation. Here we show that positively charged membrane interactive compounds (polylysine & doxorubicin) are able to inhibit PG dependent translocation of the OmpF-Lpp signal sequence mutants but not PG independent translocation. Doxorubicin is also shown to bind more efficiently to liposomes containing increased levels of anionic lipid indicating that in these assays it may be inhibiting translocation by preventing electrostatic interaction between the anionic lipid head group and the positively charged signal sequences. PMID- 8504854 TI - Isolation and characterization of PSII core complexes from a brown alga, Laminaria saccharina. AB - PSII-enriched particles, active for DCIP-reduction, were prepared from Laminaria saccharina chloroplasts, and PSII core complexes were further purified by ion exchange chromatography. They contained several polypeptides, four of them cross reacting with antibodies raised against CP47, CP43, D1 and D2 of green plants. A second chromatography was required to separate: (i) a core antenna, composed of 51 kDa polypeptide subunits, binding 11 beta-carotene, 4 chlorophyll (Chl) c and 7 fucoxanthin for 100 Chl a, and reacting with CP47 antibodies; and (ii) a reaction center complex consisting of two main polypeptides of 34 and 36 kDa. The pigment stoichiometry was of 5 Chl a and 0.5 beta-carotene for 2 pheophytin a. The 34 and 36 kDa components cross-reacted with anti-D1 and anti-D2 antibodies, respectively. The presence of cytochrome b-559 was substantiated by spectrophotometry. PMID- 8504855 TI - Efficient transient expression system based on square pulse electroporation and in vivo luciferase assay of fertilized fish eggs. AB - Electroporation mediated DNA transfer into fish eggs has been improved by using a train of square pulses. Fertilized eggs of African catfish (Clarias gariepinus), zebrafish (Brachydanio rerio) and rosy barb (Barbus conchonius) were dechorionated enzymatically followed by application of pulses. Efficiency of plasmid DNA delivery was significantly increased by applying multiple pulses on dechorionated eggs. Optimization of physical parameters such as field strength, pulse width and pulse numbers resulted in reproducible transient expression in 25 50% of embryos and larvae by using the firefly luciferase and the E. coli beta galactosidase (lacZ) genes both driven by CMV IE1 promoter. Temporal luciferase expression was assayed using both qualitative (sheet film) and quantitative (scintillation counting) methods in developing embryos and fry in vivo. Spatial expression of lacZ was assayed by histochemical staining. A number of embryos revealed foreign gene product also localised in the vegetal pole of the embryo. PMID- 8504856 TI - Glyceraldehyde-3-phosphate activates auto-ADP-ribosylation of glyceraldehyde-3 phosphate dehydrogenase. AB - Nitric oxide was recently demonstrated to stimulate ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Our studies on the effect of glyceraldehyde-3-phosphate (GA3P), the natural substrate of dehydrogenase activity of GAPDH, indicated GA3P to be another very potent activator of ADP ribosylation of the enzyme. GA3P was able to activate ADP-ribosylation only in the presence of DTT. The action of GA3P was associated with inhibition of GAPDH dehydrogenase activity. Ka for GA3P was at least 50-fold lower and maximal activation was somewhat higher than these values for other aldehydes that were also able to enhance GAPDH ADP-ribosylation in the presence of DTT. ADP ribosylation was blocked by carboxamidomethylation of the essential cysteine SH group. The bond between the prelabeled protein and ADP-ribose was resistant to hydrolysis with hydroxylamine and HgCl2, suggesting that a lysine epsilon-amino group is the target for ADP-ribosylation. PMID- 8504857 TI - Interaction of NBD-talin with lipid monolayers. A film balance study. AB - Fluorescently labelled smooth muscle talin like native talin interacts with negatively or partly negatively charged lipid monolayers. This was measured in time/area diagrams using the film balance technique combined with fluorescence imaging after double photolabelling of talin and phospholipids. PMID- 8504858 TI - A structural model for the glutamate-specific endopeptidase from Streptomyces griseus that explains substrate specificity. AB - We present a model for the three-dimensional structure of the glutamate-specific endopeptidase from Streptomyces griseus based on the crystal structures of other bacterial proteases of the trypsin family. For the first time a structural model is described which attempts to explain the basis of P1 glutamate specificity in serine proteases. Several important changes to the S1 pocket with respect to other members of the family of different specificity are described. Of particular interest is the presence of a histidine at position 213 and the substitution of Arg-138 by lysine. Other biochemical evidence concerning substrate preferences can be rationalized on the basis of the model. PMID- 8504859 TI - Calvasculin, as a factor affecting the microfilament assemblies in rat fibroblasts transfected by src gene. AB - Cell transformations accompany alterations in cell morphology and microfilament patterns. Calvasculin encodes mRNA termed pEL-98, 18A2, 42A, p9Ka, or mts1, found to be elevated in several metastatic cell lines. We report the elevation of calvasculin expression in SR-3Y1 cells, which show disappearance of ordered microfilaments, compared to that in 3Y1 cells and that the similar distribution of calvasculin to that of actin filaments. Interestingly, calvasculin co sediments with F-actin and bundles actin filaments in a Ca(2+)-dependent manner. This activity, along with the elevation of calvasculin following transformation, suggests that the disorganization of filaments in SR-3Y1 cell is due to the cross linking activity of calvasculin. PMID- 8504860 TI - Purification and functional characterization of beta-adrenergic receptor kinase expressed in insect cells. AB - The beta-adrenergic receptor kinase mediates agonist-dependent phosphorylation of beta-adrenergic receptors, which is thought to represent the first step of homologous desensitization. We have expressed bovine and human beta ARK1 in Sf9 cells and purified them to apparent homogeneity in milligram quantities. The Km values of the enzyme were 3.8 microM for rhodopsin and 22 microM for ATP; the Vmax-value was 9.9 mol phosphate/mol beta ARK/min. These data indicate that the two recombinant kinases were at least as active as preparations previously obtained from bovine brain. There were no differences in the functional activity of human and bovine beta ARK. PMID- 8504861 TI - Peroxidase-catalyzed co-oxidation of indole-3-acetic acid and xanthene dyes in the absence of hydrogen peroxide. AB - The effect of xanthene dyes on the chemiluminescence from the aerobic indole-3 acetic acid (IAA) oxidation, catalyzed by horseradish peroxidase (HRP), was studied. The rate of IAA oxidation and dye destruction were controlled. It was found that the addition of dyes to the IAA/HRP/O2 system resulted in: (i) the appearance of emission in the region of dye fluorescence, (ii) an increase of the total chemiluminescence intensity, (iii) a decrease of the emission duration, (iv) the acceleration of IAA oxidation, and (v) slow bleaching of the dyes. The experimental results lead to the conclusion that all spectral and kinetic variations of the chemiluminescence from the IAA/HRP/O2 system which are caused by the addition of xanthene dyes, are the result of IAA-dye co-oxidation. Earlier published reports regarding energy transfer from electronically excited species, generated in the IAA/HRP/O2 system, to the xanthene dyes seem to be erroneous. PMID- 8504862 TI - Mutational analysis of the specific priming signal essential for DNA replication of the broad host-range plasmid RSF1010. AB - To analyze the RSF1010-specific priming mechanism, a library of randomly mutagenized ssiA sequences was constructed by chemical synthesis using mixed nucleotide phosphoramidites. Synthetic ssiA sequences with the single base substitutions were assayed for the SSI activity in E. coli JM109 expressing RepB' primase. It was demonstrated that the activity of ssiA was damaged markedly by single base-substitutions within the possible stem-loop structure and its 3' flanking region. It is conceivable that these domains are critical in recognition and primer synthesis by RepB' primase. PMID- 8504863 TI - 1H and 15N assignments and secondary structure of the Src SH3 domain. AB - The 1H and 15N sequential assignments of the Src SH3 domain have been determined through a combination of 2D and 3D Nuclear Magnetic Resonance (NMR) methods. The secondary structure of the protein has been identified based on long-range NOE patterns. The SH3 domain of Src consists largely of six beta-strands that form two anti-parallel beta-sheets. PMID- 8504865 TI - Key elements of food contamination monitoring programmes. AB - The key elements of programmes for monitoring food contamination are reviewed in relation to their purposes, scope and priorities. Attention is drawn to the requirements and quality assurance of procedures for sampling and analysis, and methods of handling and processing analytical surveillance data. The benefits to be derived from national monitoring programmes are improved food safety, warning of problems of contamination, provision of intake data for evaluation of health hazards, better management and use of natural resources, supply of data on environmental pollution and reliable information on food safety for the public, and provision of a means of checking the effectiveness of regulatory mechanisms and planning technological developments. PMID- 8504864 TI - Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types. AB - Xylitol dehydrogenase encoded by gene XYL2 from Pichia stipitis is a member of the medium-chain alcohol dehydrogenase family, as evidenced by the domain organization and a distant homology (24% residue identity with the human class I gamma 1 alcohol dehydrogenase). Much of a loop structure is missing, like in mammalian sorbitol and prokaryotic threonine dehydrogenases, many additional differences occur, and relationships are closest with the sorbitol dehydrogenase, the equivalence of which in P. stipitis may actually be the xylitol dehydrogenase. A second P. stipitis gene, also cloned and corresponding to a xylitol dehydrogenase, is highly different from XYL2, but encodes an enzyme with structural properties typical of the short-chain dehydrogenase family, which also contains an alcohol dehydrogenase (from Drosophila). Thus, yeast xylitol dehydrogenases, like alcohol and polyol dehydrogenases from other sources, have dual derivations, combining similar enzyme activities in separate protein families. In contrast to the situation with the other enzymes, both forms of xylitol dehydrogenase are present in one organism. PMID- 8504866 TI - Handling toxicoses of unknown origin. AB - A strategy is presented for investigating toxicoses of unknown origin and following a disease-oriented approach. The strategy is derived from and illustrated by experience of three large scale outbreaks of disease involving aflatoxicosis in India, intoxication by pyrrolizidine alkaloids from Heliotropium spp. in Afghanistan and from Crotalaria spp. in India. Investigation of such cases involves a descriptive phase (case definition, descriptive pattern of disease), hypothesis generation (based on pathologic studies and indications from environmental and epidemiological investigations), hypothesis testing and confirmatory studies. After establishing a causal relationship, steps need to be taken to transmit information to health authorities, to disseminate knowledge to health delivery personnel and the general public, to identify borderline cases and plan management, to identify mechanisms of exposure/contamination and relevant measures to remove or minimize exposure to the causal agent. PMID- 8504867 TI - Dietary intake, levels in food and estimated intake of lead, cadmium, and mercury. AB - Since 1980, systematic efforts have been made by the Joint UNEP/FAO/WHO Food Contamination Monitoring Programme to collect information on dietary intake of various contaminants, exemplified by lead, cadmium and mercury. In 1980-88, average adult intakes of lead varied from 1 to 63 micrograms/kg bw/week, approaching or exceeding the Provisional Tolerate Weekly Intake (PTWI) of 25 micrograms/kg bw in four countries providing data. Major sources in food and drinking water differed from country to country. A downward trend was observed consequent on reduction in use of lead-soldered cans and of lead in petrol. Few countries provided data on intakes by infants and children (more vulnerable groups) but the mean exceeded the PTWI in three countries, heavily influenced by levels in water and lowest in infants consuming only breast milk. Average adult intakes of cadmium were, with one exception, below the PTWI of 7 micrograms/kg bw; intakes by children were higher on a body weight basis but still within the PTWI in countries supplying data. Highest levels occurred in offal (mean 320 micrograms/kg) and shellfish (200 micrograms/kg) but, because of amounts consumed, reduction of concentrations in cereals, roots and tubers would be most effective. Important sources of contamination included phosphate fertilizer sewage sludge, plated/galvanized equipment, enamels and glazes. For mercury, average intakes were below the PTWI (300 micrograms/person; 200 micrograms/person or 3.3 micrograms/kg bw as methylmercury) for adults and for breast-fed infants. Contributions from fish varied from 20 to 85%; in some countries because of different dietary habits, cereals or meat may contribute similar amounts. Because of inadequate data on food other than fish, intake estimates are biassed and sometimes based solely on typical levels in fish. PMID- 8504868 TI - Industrial chemical contamination of foods. AB - The chemical contamination of foods via industrial activity is varied and widespread with regard to both chemical and occurrence. Such contamination can arise by accident, by intent from regular ongoing industrial activity, and even from subsequent use of manufactured products themselves. The key factors in assessing whether a problem exists within a particular country are recognition and awareness that a problem can exist and the capability to define the extent and severity of the problem. Both factors are heavily dependent on the availability of well-equipped food control laboratories staffed by dedicated and competent personnel. In some situations the analytical techniques required are 'state of the art' involving sophisticated and expensive separations and determinations with extensive quality control procedures. In others, the techniques are much less complicated. In both, however, the production of valid data is paramount. To illustrate some of these differences in approach, details of ongoing Canadian programmes on polychlorinated dibenzo-dioxins and -furans in effluents from pulp and paper mills and on the migration of chemicals from packaging materials are presented. PMID- 8504869 TI - Diet/toxin interactions. AB - Biotoxins derived from bacteria, fungi and algae in food play an important role for development of diseases of unknown aetiology. Furthermore, dietary components modulate their toxicity and carcinogenicity. Current progress on their mode of action postulated the contribution of cytochrome P-450 system as well as oxygen radicals, and phosphoprotein phosphatases are the target of several tumour promoters. For prevention of biotoxin-mediated development of diseases, a detailed study and information on biological function of dietary components and a possible association between diet/toxins are needed. PMID- 8504870 TI - Mycotoxins in review. AB - The putative involvement of mycotoxins in human diseases, including cancer, is reviewed with reference to ergotism, citreoviridin toxicosis, alimentary toxic aleukia, stachybotryotoxicosis, Balkan endemic nephropathy and aflatoxicoses. Analytical and sampling problems in determining the occurrence of and exposure to mycotoxins are discussed against the background that over 300 mycotoxins have been identified, produced by some 350 fungal species, and that the potency of some of them demands the quantitation of extremely small quantities of analyte. Mycotoxins associated with food and originating from Alternaria, Aspergillus, Fusaria, Penicillia and Claviceps spp. are reviewed with reference to the toxicological, regulatory and economic issues arising. It is concluded that continued efforts are needed to: identify and quantify human/animal exposure; estimate health risks and make defensible risk-benefit judgements; develop sampling plans based on experimental observation; arrive at agreed regulatory levels based on legitimate sampling plans, analytical capabilities and economic considerations; develop procedures for disposal of contaminated lots; and develop plant varieties resistant to fungal invasion. PMID- 8504871 TI - Rationale for regulatory programmes for mycotoxins in human foods and animal feeds. AB - Currently, more than 50 countries have enacted or proposed regulations for mycotoxins in food and feed. There are various factors that may influence the establishment of tolerances for certain mycotoxins, such as the availability of toxicological data, the availability of data on dietary exposure, the distribution of mycotoxins over commodities, legislation of other countries with which trade contacts exist, and the availability of methods of analysis. In practice, only few countries have formally presented the rationale for the need to regulate, or for the selection of a particular maximum tolerated level, as a recent international enquiry demonstrated. Most of the limits for aflatoxins in food were based on rather vague statements of the carcinogenic risk for humans. There was a general consensus that exposure to a potential human carcinogen that could not be totally avoided should be limited to the lowest practical level. Several countries made a claim to a hazard evaluation (Belgium, Canada, India, The Netherlands, Switzerland, South Africa, United Kingdom, United States), although specifics were rather scarce. No rationales for setting limits for other mycotoxins were provided, except for Canada, where risk assessment was done for deoxynivalenol, zearalenone and ochratoxin A. It is apparent that in most countries either the scientific basis for regulation of mycotoxins is non existent, or the science has not been fully utilized. PMID- 8504872 TI - Recent advances in analytical methods for mycotoxins. AB - Recent advances in analytical methods are reviewed using the examples of aflatoxins and trichothecene mycotoxins. The most dramatic advances are seen as being those based on immunological principles utilized for aflatoxins to produce simple screening methods and for rapid specific clean-up. The possibilities of automation using immunoaffinity columns is described. In contrast for the trichothecenes immunological methods have not had the same general impact. Post column derivatization using bromine or iodine to enhance fluorescence for HPLC detection of aflatoxins has become widely employed and there are similar possibilities for improved HPLC detection for trichothecenes using electrochemical or trichothecene-specific post-column reactions. There have been improvements in the use of more rapid and specific clean-up methods for trichothecenes, whilst HPLC and GC remain equally favoured for the end determination. More sophisticated instrumental techniques such as mass spectrometry (LC/MS, MS/MS) and supercritical fluid chromatography (SFC/MS) have been demonstrated to have potential for application to mycotoxin analysis, but have not as yet made much general impact. PMID- 8504873 TI - Perspectives on mycotoxin decontamination procedures. AB - Unquestionably, prevention is the best method for controlling mycotoxin contamination. Should the contamination occur, however, the hazard associated with the toxin must be removed if the product is to be used for food or feed purposes. Decontamination procedures currently used are based on (a) physical, chemical, or biological removal, or (c) physical or chemical inactivation. Ammoniation of corn, peanuts, cottonseed, and meals to alter the toxic and carcinogenic effects of aflatoxin contamination has been the subject of intense research effort by scientists in various government agencies and universities worldwide. Engineers have devised workable systems of treatment of whole seeds, kernels, or meals; chemists have identified and characterized products formed from the reaction of aflatoxin B1 with ammonia with and without a meal matrix; biochemists have studied the biological effects of these compounds in model systems; and nutritionists have studied animal responses to rations containing ammoniated or non-ammoniated components. This review describes these studies as well as other potentially useful decontamination processes. The results of aflatoxin/ammonia decontamination research demonstrate the efficiency and safety of ammoniation as a practical solution to aflatoxin detoxification in foods and animal feeds. PMID- 8504874 TI - Assessment of human exposure to chemical contaminants in foods. AB - One of the most important factors in assessing risk to human health from potentially harmful chemicals in foods is the availability of good data on the exposure of the public to such substances. The means of acquiring these data generally involves monitoring programmes using appropriate sampling procedures and reliable analytical methods for measuring the compounds of concern in a variety of substrates. Two approaches are generally employed: a biological monitoring programme which measures substances in human fluids and tissues, and a food analysis monitoring programme, preferably a total diet study, wherein food is prepared for consumption prior to analysis. The choice of approach to use and chemicals to monitor depend on the situation within a particular country. The analysis of food has the advantage of short term impact since problems can be identified relatively quickly and control measures established. Biological monitoring on the other hand tends to indicate both accumulated and current exposure from all sources, including air, water and food. In Canada both approaches have been used for a number of years with major surveys of human milk and adipose tissue, and the total diet study, being conducted approximately every five years. Details of these programmes together with some of the pertinent findings are presented. PMID- 8504875 TI - International coordination and validation of analytical methods. AB - Most experimentation dealing with analytical methodology in the physical and biological sciences has been conducted within a single laboratory. Method validation by other laboratories was considered not only unnecessary but also detrimental because, in the words of one commentator, 'the results are too variable'. Within the last two decades, however, largely as a result of the requirements of international environmental and food standards programmes, it has become increasingly apparent that a collaborative interlaboratory study is the only way to estimate the variability characteristics of methods of analysis as performed by the typical population of laboratories using the methods. To obtain a common basis for measuring the statistical characteristics of analytical methods, representatives of almost two dozen international organizations meeting in Geneva, in May 1987, approved by consensus a protocol for the design and interpretation of data from collaborative studies of chemical methods of analysis. PMID- 8504876 TI - Recent methods for detection of seafood toxins: recent immunological methods for ciguatoxin and related polyethers. AB - A brief summation of the methods for detection of each of the marine toxins is presented in this report. The toxins are brevetoxin (PbTx), palytoxin (PTX), okadaic acid (OA), paralytic shellfish toxins (PSP) and ciguatoxin (CTX). The immunological and biotechnical procedures developed for each of these toxins are reviewed. Details of the recent methodology (solid-phase immunobead assay) for detection of ciguatoxin and related polyethers with monoclonal antibodies and receptors are presented. The capabilities of immunological technology for assessment of toxins in seafood products are promising and will probably be widely used in the future for seafood monitoring. PMID- 8504877 TI - Immunological studies using monoclonal antibodies for detection of low dalton marine toxins. AB - The general methodology employed in the development of an immunological assay system is initially described. These include: (a) the methods and reagents used for coupling low dalton epitopes; (b) selection of appropriate immunogenic carriers; (c) mode of administration and choice of animal; and (d) the method of assessing the antibody produced. The background and methodology, using ciguatoxin as a model, are presented. The stick enzyme immunoassay (S-EIA) has proven of value to evaluate implicated fish for verification of ciguatera poisoning and for screening of fish associated with ciguatera prior to consumption. No false negatives have occurred with the stick enzyme immunoassay system to date. PMID- 8504878 TI - Importance of international cooperation in food safety. AB - All countries need to ensure that national food supplies are safe, of good quality and available in adequate amounts at affordable prices to ensure good nutrition and health for all population groups. The enforcement of food standards by efficient national food control authorities in domestic markets and at the points of import and export has been increasingly recognized as a means of raising the value of exported goods by reducing the number of rejected or reconditioned consignments, and of ensuring the safety of the food and its acceptability by the final consumer. However, those national efforts have sometimes induced some non-tariff barriers to food trade and distribution. In addition, new developments in the technologies of food production, processing and marketing pose a new challenge to ensure safety of food. The strengthening of national food control infrastructures in particular in developing countries including the strengthening of staff capabilities, the need for harmonization of food at international levels, the need for collection and exchange of data on food control and food contamination issues are essential elements to ensure food safety in the world. International cooperation has an important role to play in achieving these essential elements. PMID- 8504879 TI - Genetic determinants of type 2 diabetes mellitus: lessons learned from family studies. AB - Non insulin dependent diabetes mellitus (Type 2) is a multifactorial disease, with a polygenic inheritance and environmental factors contributing to its clinical expression. The search for the genetic determinants of Type 2 diabetes began when several genes involved in the mechanisms of insulin secretion or action were cloned, localized in the human genome, and when informative polymorphisms were described within or in the vicinity of these genes. It then became possible to compare, in groups of patients and normoglycaemic controls from various populations, the frequency of the different alleles of polymorphic markers of various candidate genes (e.g. insulin, insulin receptor, glucose transporters). The conflicting results observed in these studies can be ascribed to the small size of the population samples, to the genetic heterogeneity of Type 2 diabetes mellitus, but also to the methodology used therein. Indeed, these studies searched for a correlation between the frequency of certain alleles or genotypes and the phenotype of diabetes (studies of associations in affected populations compared to healthy controls). However in order to attribute to a gene the responsibility for a disease it is necessary to demonstrate the cotransmission in affected kindreds of a morbid allele of the gene along with the disease (familial or linkage analysis). The aim of this review is to summarize the results of family studies of Type 2 diabetes and Maturity Onset Diabetes of the Young (MODY), particularly with concern to the mutations described in candidate genes, and the implication of glucokinase in these disorders. PMID- 8504880 TI - Assessment of long-term (1 year) graft survival and metabolic and hormonal changes after intrasplenic canine pancreatic microfragment transplantation. AB - Few data have been published so far on the long-term metabolic and endocrine consequences of intrasplenic islet autografts in dogs and the available information mainly deals with glucose response and, more rarely, insulin secretion during intravenous glucose tolerance tests. The effect of islet transplantation on glucagon levels has never been reported. In this study we measured glucose, insulin, total glucagon, and pancreatic glucagon in dogs before and after (up to 1 year) intrasplenic islet autografts. Pancreata were retrieved from 21 adult dogs and the islets were isolated by collagenase digestion. The endocrine tissue was transplanted into the spleen by direct pulp injection. Autografts resulted in normoglycaemia in 19 out of 21 dogs (90%). Among the successfully transplanted dogs, the percentage of functioning grafts was 71% at 1 year. The metabolic and hormonal results of the follow-up showed that fasting glucose and insulin concentrations did not differ significantly before and after transplantation. However, glucose tolerance and insulin secretion on intravenous glucose tolerance testing were significantly reduced in transplanted animals. Fasting total and pancreatic glucagon, and their integrated releases during the test did not change significantly after islet transplantation. These results demonstrate that: 1) long-term function of intrasplenic canine islet autografts can be achieved in high percentages; 2) autotransplanted animals have normal or near normal fasting glucose and insulin levels, but reduced glucose disappearance and insulin secretion on intravenous glucose tolerance tests; 3) normal glucagon secretion is a feature of successful islet grafts. PMID- 8504881 TI - The Diva System, a computerized diary, used in young type 1 diabetic patients. AB - The purpose of the present study was to evaluate the clinical efficiency of a computer bases registration- and analysis-system, Diva System, designed for the support of diabetes care. Fifty six boys aged 14-20 years with a diabetes duration of more than two years and HbA1c above 8% were allocated to one of three groups: 1) Diva group: Diva supported intensified outpatient regimen n = 9, 2) Control group A: Intensified outpatient control n = 7, and 3) Control group B: Conventional outpatient control n = 40. The patients were followed for a period of twelve months, in which the Diva group patients used the system during the first six months. In this period the HbA1c decreased significantly in the Diva group, 1.6% p < 0.001, compared to only a slight decrease in the two control groups, 0.3 and 0.4% respectively, ns. IN CONCLUSION: The Diva System seems to be a supportive tool, which might assist the patients to better self care and thereby to improved metabolic control. However, the use of the computer system is time consuming. PMID- 8504882 TI - Weight loss reverses secondary failure of oral hypoglycaemic agents in obese non insulin-dependent diabetic patients independently of the duration of the disease. AB - The aim of the present study was to evaluate whether reduction of body weight is able to restore sensitivity to oral hypoglycaemic agents in obese non-insulin dependent diabetic patients with secondary failure of to the anti-diabetic drugs. 80 obese patients (BMI approximately 30 kg/m2) with Type 2 diabetes lasting 1-30 years and showing hyperglycaemia for at least 3 months (51 on insulin, 29 on oral drugs) received an 800 kcal diet for 20-24 days, lost about 6.3% BMI, and returned to euglycaemia; 22 obese euglycaemic Type 2 diabetes patients (9 on insulin, 13 on oral therapy) underwent the same treatment, and lost approximately 8.3% BMI. As a result insulin could be withdrawn in 18 out of 60 patients and reduced (from 0.5 to 0.2 U.kg day) in the remaining patients. Oral therapy could be withdrawn in 17 out of 42 cases and reduced (from 12.1 to 8.6 mg glibenclamide/day) in the remaining cases. As a control group, 20 non obese (BMI < 24.0 kg/m2) hyperglycaemic Type 2 diabetic patients (10 on oral hypoglycaemic agents, 10 on insulin) with Type 2 diabetes lasting 1-26 years, underwent the same dietary regimen, lost about 3.2% of body weight, but could not withdraw insulin, which had to be started in 6 previously oral hypoglycaemic drugs treated patients. Systolic and diastolic blood pressure and serum cholesterol and triglyceride levels also decreased in obese, but not in non-obese Type 2 diabetes patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504883 TI - Pharmacological interference with phospholipase A2 activity reveals mechanistic differences between glucose and glyceraldehyde induced insulin release: implication for coupling of glucose metabolism to phospholipase A2 activity. AB - Prostaglandin E2 levels in isolated rat islets were increased from 64 +/- 11 pg/30 islets when incubated in medium containing 2 mM glucose to 115 +/- 9 pg/30 islets in medium containing 20 mM glucose. In contrast, glyceraldehyde (10 mM) reduced prostaglandin E2 levels to 29 +/- 6 pg/30 islets. Inhibition of glucose metabolism by mannoheptulose (10 mM) abolished the stimulatory effect of glucose on prostaglandin E2 levels and inhibited glucose-induced insulin release. The cyclooxygenase inhibitor, flurbiprofen (20 microM), did not affect insulin release caused by glucose or glyceraldehyde. In the presence of 1 mg/ml bovine serum albumin, insulin secretion induced by 20 mM glucose (6.9 +/- 1.1% of islet insulin content) was reduced by the lipoxygenase inhibitor BW755 C (20 microM) to 3.1 +/- 0.6%, and by the phospholipase A2 inhibitor, p-bromophenacyl bromide (10 microM), to 2.1 +/- 0.8%. In the absence of bovine serum albumin the inhibitory action of BW755 C and p-bromophenacyl bromide on glucose-induced insulin release was significantly more pronounced. These drugs whether in the presence or absence of bovine serum albumin, did not affect glyceraldehyde-stimulated insulin secretion. Glyceraldehyde (10 mM), potentiated glucose-induced insulin release in the presence of 2-8 mM glucose, but not for 10-20 mM glucose. Although the phospholipase A2 activator, melittin, initiated insulin release in the presence of 2 mM glucose and enhanced 10 mM glyceraldehyde-stimulated insulin secretion it had no effect on 20 mM glucose-induced insulin release. These two stimulatory effects of melittin on insulin release were totally abolished by p-bromophenacyl bromide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504884 TI - Effect of metformin treatment on glucose tolerance and glomerulosclerosis in KK mice. AB - Non-obese KK mice, aged 90-100 days, demonstrating an abnormal tolerance to glucose, hyperinsulinaemia with insulin resistance and glomerulosclerosis were treated with either water (control N = 10) or metformin (N = 15), a biguanide, orally at a concentration of 50 mg/kg twice daily for 16 weeks. Oral glucose tolerance was performed at 7 weeks. Only 10 of 15 metformin-treated mice (responders) improved their oral glucose tolerance. The remaining 5 mice (non responders) did not improve their tolerance to the oral glucose load. A repeated oral glucose tolerance test at 16 weeks showed similar results. Blood lactate and insulin levels were similar in all 3 groups of mice. At sacrifice, responders had significantly less glomerulosclerosis compared to control mice. No difference in the incidence of glomerulosclerosis was found between control mice and non responders. The data suggest that chronic metformin treatment improves glucose tolerance in 70% of KK mice without increasing blood lactate or insulin levels. This improvement in glycaemic control is associated with a lesser incidence of glomerulosclerosis in KK mice. PMID- 8504885 TI - Insulin resistance and excess weight in adolescent insulin-dependent diabetic girls. AB - Insulin dependent diabetic adolescent girls show a tendency towards excess weight. The relationship between insulin resistance and body mass index (BMI) was investigated in 23 Type 1 adolescents aged 13-20 yr. These patients body mass indexes spanned from 19.8 to 30.5. Excess weight was evaluated using Z-scores, corrected for age with reference to french standards. 9 patients with a Z-score greater than 2 were considered as obese. Insulin sensibility was measured using the hyperinsulinaemic euglycaemic clamp (insulin infusion rate, 1 mU kg-1 min-1). The mean glucose infusion rate during the clamp was low in the diabetic girls (2.29 +/- 1.35 mg kg-1 min-1), confirming the existence of insulin resistance. However, the degree of insulin resistance was not correlated with the excess in weight (glucose infusion rate, 2.23 +/- 1.24 vs 2.33 +/- 1.46 mg kg-1 min-1 in the obese and the non-obese patients, respectively). None of the factors which influence on insulin sensitivity could explain this lack of correlation, the obese patients showing greater daily insulin doses (1.36 +/- 0.22 vs 1.22 +/- 0.25 unit kg-1 day-1) and worse metabolic control (Hba1C, 10.9 +/- 1.4 vs 10.2 +/ 2.0%). Insulin resistance was significantly correlated with free fatty acid levels during the clamp. PMID- 8504886 TI - [The insulin pen injector: toward its rational development and utilization]. PMID- 8504887 TI - [Transgenic animals and their means of application]. PMID- 8504888 TI - Science and spasticity. PMID- 8504889 TI - Photophobia and cortical visual impairment. AB - Photophobia, or intolerance of light, is not completely understood as a symptom. It has been divided into ocular and central types. This study shows that persistent, usually mild, photophobia occurs in about one-third of children with cortical visual impairment (CVI). When the CVI is congenital the photophobia is present from birth, and when it is acquired the sensitivity to light appears immediately after the brain insult. The intensity of photophobia tends to diminish with time and occasionally it may even disappear. The pathophysiology is unclear, as in all other neurological disorders associated with photophobia. PMID- 8504890 TI - Visually impaired children and haptic intelligence test scores: intelligence test for visually impaired children (ITVIC). AB - This paper reports the results of verbal and haptic intelligence tests for the whole population of the visually impaired, braille-educated Dutch children and Dutch-speaking children in Belgium. The scores of children with and without usable vision generally confirmed expectations. Children with usable vision had higher spatial test scores. Those without usable vision did better on verbal memory tests and school-achievement tests for writing accuracy and technical reading. Children in regular or integrated education scored higher on verbal, reasoning and school-achievement tests. Evaluation of the effect of systematically varied task factors in four spatial tests indicated that, for two of the tests, having usable vision interacted with the task factors. PMID- 8504891 TI - Septo-optic dysplasia: the clinical insignificance of an absent septum pellucidum. AB - Neurodevelopmental assessments were performed on seven patients with optic nerve hypoplasia and absence of the septum pellucidum on MRI. The evaluation included neurological status, language development, neuropsychological functioning, and behavioral and emotional adjustment. Six of the seven were found to have normal cognitive development, intact neurological status, normal language development and age-appropriate behavior. Abnormal findings included early poor motor coordination, which was felt to be closely related to decreased visual acuity, as well as subtle visual attentional problems which occurred even in patients who had normal vision in one eye. Congenital absence of the septum pellucidum was not associated with significant intellectual, behavioral or neurological deficits in the majority of these patients. PMID- 8504892 TI - Proton spectroscopy of the neonatal brain following hypoxic-ischaemic injury. AB - Proton magnetic resonance spectroscopy was used to examine, within the first month of life, the brains of 11 infants born at term--10 with signs of hypoxic ischaemic encephalopathy (HIE) and one who was neurologically normal at birth. All the infants had peak resonances on their spectra which could be assigned to N acetyl-aspartase (NAA), choline-containing compounds (Cho) and creatine plus phosphocreatine (Cr). When neurodevelopmental outcome at one year was correlated with initial spectroscopy findings, the NAA/Cho and NAA/Cr ratios reflected clinical outcome. This study suggests that proton spectroscopy not only provides new information about biochemical changes occurring in the brains of infants with HIE, but also may help to predict outcome within the first month of life. PMID- 8504893 TI - Short-term efficacy of tympanostomy tubes for secretory otitis media in children with Down syndrome. AB - Twenty-four children with Down syndrome, aged six to 14 years, were tested with audiometry six to nine weeks after insertion of tympanostomy tubes for bilateral secretory otitis media (SOM). There was no improvement in hearing in 40 per cent of ears, compared with only 9 per cent of ears in 21 age-matched controls with bilateral SOM. Tympanostomy tubes for SOM in children with Down syndrome have a high short-term failure rate, which should be explained to the parents before insertion, and the children should have audiometry tests shortly after the operation. Persistent hearing-loss may require the fitting of hearing aids. Management should involve ensuring that the children are in a situation in which they can hear as well as possible, and making allowances for the hearing impairment. PMID- 8504894 TI - Postural behaviour of term SGA and AGA newborn infants. AB - The authors studied the body posture at rest of 15 healthy term infants with birthweights appropriate for gestational age (AGA) and 15 infants who were small for gestational age (SGA). In both groups, there was wide inter-individual variability in postural behaviour. Apart from a preference for a position with all limbs in abduction between 1 and 90 degrees, independent of the degree of flexion or extension and internal/external rotation, no dominant preference posture could be seen for either group. The SGA infants showed a more flexed position of the arms, compared with the AGA group. One of the factors contributing to this difference might be the influence of intra-uterine malnutrition on the development of the central nervous system. PMID- 8504895 TI - Proximal femoral resection for older children with spastic hip disease. AB - Thirteen patients (19 hips) who underwent proximal femoral resection arthroplasty for symptomatic subluxation or dislocation of the hip were reviewed retrospectively. All had severe neurological involvement, and when older were non ambulatory with spastic quadriplegia or myelodysplasia. Resections were either at the level of the neck (nine hips) or in the subtrochanteric region (10 hips). The latter provided a better operative result than did the former. Poor clinical results noted were continued pre-operative pelvic obliquity, postoperative adduction contracture, and bony contact between the pelvis and the remaining proximal femur or its heterotopic ossification. PMID- 8504896 TI - Stereotypical lower-limb movements of a child with Arnold-Chiari malformation. AB - A one-year-old boy with Arnold-Chiari malformation associated with hydrocephalus and meningocele presented with characteristic stereotypical alternating movements of the lower limbs. The movements were not considered to be epileptic, but to derive from a locomotion pattern-generator in the spinal cord. Persistence of the stereotypical movements implied some deficit of the upper-motor pathways, although the lesion responsible could not be determined. PMID- 8504897 TI - Latex anaphylaxis during spinal surgery in children with myelomeningocele. AB - Intra-operative anaphylaxis to latex involves cutaneous, respiratory and circulatory changes which may prove fatal if not promptly recognized and treated. It is estimated that 18 to 40 per cent of children with spina bifida may be affected by latex allergy. Current tests available lack sufficient sensitivity and specificity to be recommended as routine screening measures, therefore any allergic history in children with myelomeningocele should alert the clinician to the possibility that severe anaphylactic reactions may occur, especially when large mucosal and pleural-peritoneal surfaces are exposed, as noted in the four reported cases. Epinephrine is the drug of choice should a Type 1 reaction occur. PMID- 8504898 TI - Infectious diseases in pregnancy, cytokines and neurological impairment: an hypothesis. PMID- 8504899 TI - Preterm birth and cerebral palsy: is tumor necrosis factor the missing link? PMID- 8504900 TI - Advances in biologically based models for respiratory tract uptake of inhaled volatiles. AB - Physiologically based pharmacokinetic models for volatile organic chemicals typically describe the respiratory tract as a single compartment in which chemicals in the alveolar air space and the arterial blood are in instantaneous equilibrium. These models also assume that the distribution of chemical in the air-stream is uniform throughout the respiratory tract and that uptake is significant only in the alveolar region. A functional role for the upper respiratory tract in the uptake of volatile chemicals has been largely ignored. While these models have worked well for chemicals with low aqueous solubility in biological fluids, systemic uptake of highly soluble volatiles is overestimated. Thus, there is a significant effort to describe the critical determinants for uptake of soluble chemicals and to formulate models with more biologically relevant descriptions of respiratory tract structure and function. Investigators have addressed this problem from several viewpoints. Airflow patterns in the respiratory tract, regional metabolism, diffusion-dependent uptake, and the cyclic nature of respiration are now being incorporated into current models. Use of dosimetric models that incorporate relevant biology for inhaled chemicals will ultimately result in more meaningful human risk assessments. PMID- 8504902 TI - Reproductive and thyroid effects of low-level polychlorinated biphenyl (Aroclor 1254) exposure. AB - As little information is available on the adverse effects of polychlorinated biphenyls (PCBs) on the reproductive system of the male rat, the current study was conducted to evaluate the effects of subchronic administration of the PCB mixture Aroclor 1254 on testicular gamete production and endocrine function. The thyroid hormone thyroxine (T4), which is critical for reproduction and development, was also measured because of the well-documented effects of PCBs on this hormone. Weanling (31-day-old) male Fischer rats were administered 0, 0.1, 1, 10, or 25 mg/kg/day Aroclor 1254 by gavage for 5, 10, or 15 weeks and necropsied. The hormones testosterone (T) and thyroxine were measured in the serum, and body weight and weights of the liver, kidney, testes, seminal vesicle plus coagulating gland, cauda epididymides, and pituitary were taken. At 10 and 15 weeks, testicular interstitial fluid (IF) was collected and T concentration in the IF was measured. Sperm motility was measured from a caudal sperm sample and sperm numbers in the testis and cauda epididymis were determined. In addition, tissues were examined microscopically for histopathological alterations. In the high-dose group, body, seminal vesicle, cauda epididymal, and pituitary weights were depressed at 10 and 15 weeks and cauda epididymal sperm numbers were reduced after 15 weeks of dosing. In contrast, testes weights, testicular sperm numbers, sperm motility, and serum and testicular testosterone levels were unaffected, even in the highest dose group (25 mg/kg/day). Aroclor 1254 administration produced histological alterations in the liver and kidney at doses of 1.0 mg/kg/day and above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504901 TI - Effects of 7,12-dimethylbenz[a]anthracene on the superantigen toxic shock syndrome toxin (TSST-1)-induced proliferation and antibody secretion by human lymphocytes. AB - Toxic shock syndrome toxin (TSST-1), a 22-kDa exotoxin secreted by Staphylococcus aureus, can act as a nominal antigen and induce proliferation and immunoglobulin secretion in human B-cells. The purpose of the present studies was to examine the effect of 7,12-dimethylbenz[a]anthracene (DMBA), a well-characterized immunosuppressant of both cell-mediated and humoral immunity in murine lymphocytes, upon the mixed lymphocyte reaction (MLR) and TSST-1-induced immune responses in human lymphocytes. The MLR, using human tonsillar lymphocytes (HTL) from four different donors, was inhibited in a dose-dependent manner from 1 to 100 microM. The IC50 for the suppression of the MLR ranged from 10 to 40 microM. TSST-1 is a potent stimulator of T-cells bearing specific VB regions on the T cell receptor (TCR). In contrast with the results from the MLR, DMBA inhibited TSST-1-induced T-cell proliferation only at 100 microM in HTL. A similar profile of activity was determined with splenic T-cells from a single donor. TSST-1 has also been demonstrated to induce specific B-cell proliferation and differentiation in the presence of irradiated T-cells. TSST-1-induced B-cell proliferation was only consistently and markedly inhibited by DMBA at 100 microM in tonsillar and splenic lymphocytes. In contrast, TSST-1-induced B-cell differentiation, as manifested by IgM and IgG secretion, was inhibited in a dose dependent manner from 1 to 100 microM DMBA in B-cells from human tonsils and spleens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504903 TI - Chronic dieldrin exposure increases hepatic disposition and biliary excretion of [14C]dieldrin in rainbow trout. AB - Previous work demonstrated that exposure of laboratory animals including fish to certain organochlorine (OC) insecticides altered the tissue distribution of a subsequent tracer dose of the same [14C]OC. In the present study, 10- to 20-g rainbow trout were exposed to 15 ppm dieldrin in the diet. Fish were subsequently challenged at 2-week intervals with an intraperitoneal injection of 0.1 mg/kg [14C]dieldrin and viscera (liver, bile, mesenteric fat, kidney, and intestine) analyzed for radioactivity, 24 hr later. After 10 and 12 weeks of dieldrin pretreatment, [14C]dieldrin was significantly elevated relative to controls in liver (200%), bile (500%), and fat (500 and 1200% for 10 and 12 weeks, respectively) of pretreated fish. Other tissues were unchanged. Chloroform/methanol extractions revealed a time-dependent increase in label disposition to carcass lipid in controls but not in pretreated fish. Altered disposition could not be explained by changes in total body lipid or induction of total cytochrome P-450 or ethoxyresorufin-O-deethylase, pentoxyresorufin-O deethylase, glutathione S-transferase, or UDP glucuronosyltransferase activities. In vivo assessment of [14C]dieldrin metabolism revealed no increase in hepatic and only a slight (22%) increase in biliary polar:nonpolar concentration ratio after 9 weeks 20 ppm dieldrin pretreatment. Results suggest that constitutive changes in liver integral to dieldrin sequestration, transport, or excretion may be an adaptive response of trout to chronic OC exposure. PMID- 8504904 TI - Acute hepatotoxic and nephrotoxic effects of chloroform in male F-344 rats and female B6C3F1 mice. AB - Previous studies demonstrated that chloroform given by oral gavage in corn oil caused an increased incidence of liver tumors in male and female mice and kidney tumors in male rats, while administration in drinking water resulted in an increased tumor incidence only in the kidneys of the male rats. The tumorigenicity of this nongenotoxic agent has been postulated to be linked with cytolethality and cell proliferation. This study examined the organ-specific toxicity of acute doses of chloroform. Male F-344 rats were given chloroform by gavage in corn oil at the bioassay doses of chloroform of 0 and 180 mg/kg body wt as well as 34 and 477 mg/kg and necropsied 24 hr later. Additional rats were given a single dose of 180 mg chloroform/kg and administered bromodeoxyuridine (BRDU) 2 hr prior to necropsy at 0.5, 1, 2, 4, and 8 days after chloroform treatment. Female B6C3F1 mice were given chloroform by gavage at the bioassay doses of 0, 238, and 477 mg/kg as well as 34 mg/kg and necropsied at 24 hr after treatment. Additional mice were given a single dose of 350 mg chloroform/kg, labeled with BRDU, and necropsied at 0.5, 1, 2, 4, and 8 days after treatment. The kidneys of male rats administered 34, 180, and 477 mg chloroform/kg exhibited mild to severe proximal tubular necrosis in a dose-dependent manner. A 20-fold increase in the labeling index (LI, the percentage of nuclei in S-phase) in the proximal tubule cells was observed 2 days after treatment with the bioassay dose of 180 mg/kg. The livers of male rats exhibited only slight to moderate multifocal centrilobular necrosis at 180 and 477 mg/kg. A 10-fold increase in the LI was observed in the liver of male rats given 477 mg/kg, but no increase was observed at the bioassay dose of 180 mg/kg. In contrast to male rats, female mice developed a dose-dependent centrilobular hepatic necrosis at 238 and 477 mg/kg. No renal lesions were observed in female mice at any dose. A peak increase in LI of 38-fold was observed in hepatocytes in the livers of female mice 2 days after treatment with 350 mg chloroform/kg, with only a 2-fold increase in LI observed in the kidneys. These data indicate that acute chloroform-induced cytolethality leads to increased cell proliferation and that the organ-specific pattern of toxicity is the same as the organ-specific pattern of tumor formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504905 TI - Modulation of c-myc gene expression in rat livers by aflatoxin B1 exposure and age. AB - A single dose of aflatoxin B1 (AFB1) caused a rapid and transient induction in c myc mRNA levels in livers derived from adult male Fischer 344 rats. The inducibility of c-myc expression by AFB1 increased with age as c-myc mRNA levels from untreated livers declined from 18-fold in 29-day-old animals to 1-fold in 39 day-old animals, relative to untreated 43-day-old control animals. A dose dependent increase in c-myc mRNA was found when 53- and 76-day-old rats were administered various AFB1 doses whereas 29-day-old animals exhibited essentially no change in c-myc mRNA levels for the doses examined. Rats were treated with multiple doses of AFB1 to induce hepatocellular carcinomas. C-myc mRNA levels were measured in rat liver samples taken during and subsequent to chronic AFB1 exposure. Characterization of the c-myc induction response at the time of AFB1 exposure revealed that a transient elevation of c-myc mRNA occurred during each (5-day) dosing period for the first 3 weeks, consistent with the acute exposure studies. RNA prepared from hepatocellular carcinomas exhibited elevated levels of c-myc mRNA compared to vehicle-treated control animals. Examination of tumors isolated from the 28-day-old animals showed that the increased c-myc mRNA observed was not the result of gene amplification or gene rearrangement. A comparison of tumor data showed that the 28-day-old animals had a 100% liver tumor incidence while the 38-day-old rats had a 20% liver tumor incidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504906 TI - Styrene inhalation toxicity studies in mice. I. Hepatotoxicity in B6C3F1 mice. AB - Studies were conducted to evaluate the toxic effects of short-term repeated styrene inhalation in B6C3F1 mice. Male and female mice were exposed to 0, 125, 250, or 500 ppm styrene, 6 hr/day, for up to 14 days. Styrene toxicity was characterized by severe centrilobular hepatic necrosis and deaths after one exposure to 500 ppm or two exposures to 250 ppm. Mortality and hepatotoxicity were not increased by additional exposures, and in surviving mice, regeneration and repair of initial hepatic injury occurred in spite of continued exposure for 14 days. A marked sex difference was observed, with male mice significantly more susceptible to styrene toxicity than females. A nonlinear dose response was observed where mortality in male and female mice was greater in the 250 ppm dose group than that in the 500 ppm dose group. Severe congestion and necrosis of the liver was present in moribund mice; hepatic congestion and serum alanine aminotransferase and sorbitol dehydrogenase were significantly greater in moribund animals. PMID- 8504907 TI - In vivo and in vitro percutaneous absorption and skin decontamination of arsenic from water and soil. AB - The objective was to determine the percutaneous absorption of arsenic-73 as H3ASO4 from water and soil. Soil (Yolo County 65-California-57-8) was passed through 10-, 20-, and 48-mesh sieves. Soil retained by 80 mesh was mixed with radioactive arsenic-73 at a low (trace) level of 0.0004 microgram/cm2 (micrograms arsenic per square centimeter skin surface area) and a higher dose of 0.6 micrograms/cm2. Water solutions of arsenic-73 at a low (trace) level of 0.000024 micrograms/cm2 and a higher dose of 2.1 micrograms/cm2 were prepared for comparative analysis. In vivo in Rhesus monkey a total of 80.1 +/- 6.7% (SD) intravenous arsenic-73 dose was recovered in urine over 7 days; the majority of the dose was excreted in the first day. With topical administration for 24 hr, absorption of the low dose from water was 6.4 +/- 3.9% and 2.0 +/- 1.2% from the high dose. In vitro percutaneous absorption of the low dose from water with human skin resulted in 24-hr receptor fluid (phosphate-buffered saline) accumulation of 0.93 +/- 1.1% dose and skin concentration (after washing) of 0.98 +/- 0.96%. Combining receptor fluid accumulation and skin concentration gave a combined amount of 1.9%, a value less than that in vivo (6.4%) in the Rhesus monkey. From soil, receptor fluid accumulation was 0.43 +/- 0.54% and skin concentration was 0.33 +/- 0.25%. Combining receptor fluid plus skin concentrations gave an absorption value of 0.8%, an amount less than that with in vivo absorption (4.5%) in the Rhesus. These absorption values did not match current EPA default assumptions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504908 TI - Acute methanol toxicity in minipigs. AB - The pig has been proposed as a potential animal model for methanol-induced neuro ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Average maximum methanol concentrations in plasma, of 3100 +/- 700 (SD), 6200 +/- 2300, and 15,200 +/- 900 micrograms/ml were reached within 0.5 to 4 hr following methanol administration in animals given 1.0, 2.5, or 5.0 g methanol/kg, respectively. The mean initial elimination half-lives of methanol were 9.0 +/- 1.6, 22.4 +/- 6.1, and 18.9 +/- 4.3 hr, for 1, 2.5, and 5.0 g/kg doses, respectively. In 3 minipigs, a transient increase in plasma formate concentration (1.74-3.40 mEq/liter vs control = 0.5 +/ 0.3 mEq/liter) occurred 4 to 30 hr following methanol administration. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuro-ocular toxicosis. PMID- 8504909 TI - Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice. AB - 1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504910 TI - Acute cardiotoxicity of nucleoside analogs FddA and FddI in rats. AB - The acute cardiotoxic potential of single dosages of FddA (2'-fluoro-2',3' dideoxyadenosine) and FddI (2'-fluoro-2',3'-dideoxyinosine) was investigated in 6 to 9-week-old rats. Both nucleoside analogs were administered orally at 1000 and 2000 mg/kg and intravenously at 500 or 1000 mg/kg. For comparative purposes, additional groups of rats received 2'-deoxyadenosine or the 2-fluororibose moiety common to both the FddA and FddI molecules. The effects of two adenosine receptor antagonists, caffeine and theophylline, on the cardiotoxicity induced by FddA were also investigated. Deaths occurred within a few hours to a few days in FddA treated rats given 2000 mg/kg orally or 500 mg/kg intravenously and in FddI treated rats given 1000 mg/kg intravenously. Microscopic examination of the hearts revealed myocardial degeneration and necrosis for all rats that died and myocardial fibrosis for many survivors. No deaths or cardiac lesions were observed after administration of 2'-deoxyadenosine or the 2-fluororibose moiety. FddA was more cardiotoxic than FddI in rats at equivalent dosages administered either orally or intravenously. Based on the anatomic findings, all deaths were attributed to cardiac lesions. The administration of high, oral dosages of caffeine and theophylline accentuated the acute cardiotoxicity of FddA in rats. PMID- 8504911 TI - Relative developmental toxicities of inhaled aliphatic mononitriles in rats. AB - The developmental toxicities of eight aliphatic mononitriles were studied in Sprague-Dawley rats after inhalation exposure for 6 hr/day, during Days 6 to 20 of gestation. The range of exposure concentrations for acetonitrile was 900 to 1800 ppm; for propionitrile and n-butyronitrile, 50 to 200 ppm; for isobutyronitrile, 50 to 300 ppm; for acrylonitrile and methacrylonitrile, 12 to 100 ppm; for allylnitrile 12 to 50 ppm; and for 2-chloroacrylonitrile, 1 to 12 ppm. Embryolethality was observed after exposure to 1800 ppm acetonitrile, 200 ppm propionitrile, 300 ppm isobutyronitrile; fetotoxicity was observed after exposure to 200 ppm propionitrile, n-butyronitrile, or isobutyronitrile, or to 25 ppm acrylonitrile in the presence of overt signs of maternal toxicity. In the absence of significant maternal toxicity, allylnitrile caused embryolethality, fetotoxicity, and clear teratogenicity at 50 ppm, and n-butyronitrile and methacrylonitrile caused fetotoxicity at 200 ppm and 100 ppm, respectively. While maternal toxicity was observed for 2-chloroacrylonitrile, it did not cause significant embryonal or fetal toxicity up to 12 ppm. PMID- 8504912 TI - Factors affecting carcinogenic potential of mixtures. AB - Historically, exposure to complex mixtures such as soot, coal tar, mineral oils, and cigarette smoke has been associated with increased cancer mortality. Benzo[a]pyrene (BaP) has been used to predict the carcinogenic potency of mixtures. Two complete carcinogenicity C3H/HEJ mouse skin bioassays were undertaken to determine the effect of low doses of BaP on the carcinogenic potential of mixtures. A toluene solution containing 0.1% each of five noncarcinogenic polycyclic aromatic hydrocarbons (PAHs), anthracene, chrysene, pyrene, fluoroanthene, and phenanthrene, produced tumors in 23% of the mice with a latent period of 73 weeks. With the addition of a 0.001% BaP to the above solution, 47% of the mice produced tumors with a latent period of 66 weeks. In the second study, coal tar in toluene, which was determined to contain 0.0006% BaP, produced tumors in 51% of mice with a latent period of 73 weeks. In both studies the BaP solutions by themselves did not produce tumors. In a third study, the 9-, 2-, and 3-methylbenz[a]-anthracene compounds were noncarcinogenic using toluene as the solvent. With the substitution of n-dodecane for toluene all three compounds produced significant numbers of tumors. The results indicate that (1) low dose levels of BaP can have an impact on the carcinogenic potential of mixtures, (2) the presence or absence of BaP is not always sufficient to account for the observed potency and the synergistic effects of other substances which might be present, and (3) that certain noncarcinogenic methylbenz[a]anthracenes can have their carcinogenic potential altered by a change in the solvent used. PMID- 8504913 TI - Bioassay for carcinogenicity of rotenone in female Wistar rats. AB - Rotenone, a pesticide extracted from the Derris root, consistently was reported by a series of investigators to have induced mammary fibroadenomas in female Wistar rats when administered ip or by gavage in a sunflower (SF) oil or SF oil:chloroform vehicle. In contrast, no less than eight bioassays done in other laboratories with rotenone or rotenone-containing powders have given consistently negative carcinogenic results when different strains or species and different modes or vehicles of administration have been used. However, these studies were not designed to address the biological reproducibility of the positive data. Thus, the present study was designed to simulate conditions of the positive studies and to investigate a possible cocarcinogenic interaction between rotenone and chloroform. Each of eight treatment groups was assigned 72 weanling female Wistar rats. Groups were (1) untreated, (2) needle puncture, (3) SF oil:10% chloroform (SF oil:chloroform), (4) 1.0 mg/kg rotenone in SF oil:chloroform, (5) 2.0 mg/kg rotenone in SF oil:chloroform, (6) SF oil, (7) 1.0 mg/kg rotenone in SF oil, and (8) 2.0 mg/kg rotenone in SF oil. Rats were injected ip 5 days a week for 8 weeks (42 injection days) and subsequently held for 16 months. The appearance of palpable tissue masses was recorded; over 50 tissues from each rat were histologically evaluated. There were no statistically significant differences in overall or individual tumor incidences among control and rotenone treated groups. Specifically, neither incidence nor time-to-palpation of mammary fibroadenoma significantly differed among control and rotenone-treated groups, regardless of the vehicle of administration. Thus, rotenone was not carcinogenic, and rotenone and chloroform did not interact to produce a carcinogenic effect in female Wistar rats in the current study. Thus, previous reports of carcinogenic activity were not reproducible under similar experimental conditions. PMID- 8504914 TI - In vitro study of catecholamine release from perifused frog adrenal slices. AB - The adrenal gland of amphibians is composed of a mixed population of adrenochromaffin and corticosteroid-secreting cells. It has previously been shown that chromaffin cells synthesize several bioactive substances (including biogenic amines and neurotransmitters) which may act locally to regulate corticosteroid secretion. In the present report, we have studied the secretory activity of adrenochromaffin cells in Rana ridibunda. Frozen sections of adrenal gland were immunolabeled with antisera against tyrosine hydroxylase or phenylethanolamine-N methyltransferase. Comparison of homologous fields on consecutive sections indicated that 77% of catecholaminergic cells produce adrenaline. The concentrations of catecholamines were measured by means of high performance liquid chromatography analysis coupled to electrochemical detection. The concentrations of dopamine, noradrenaline, and adrenaline in fresh adrenal tissue were 24 +/- 4, 763 +/- 68, and 1032 +/- 118 ng/mg wet weight, respectively. After a 12-hr perifusion period, the concentration of adrenaline in the tissue was reduced by 62%, whereas noradrenaline only decreased by 22%. The secretion rates of adrenaline and noradrenaline from perifused adrenal slices significantly diminished during the first 7 hr of the experiment and then remained relatively stable for about 10 hr. Exposure of adrenal tissue to a depolarizing concentration of potassium (55 mM) induced an immediate and substantial rise of adrenaline and noradrenaline release and a delayed increase in corticosterone output. Acetylcholine, which stimulates corticosterone secretion from frog adrenocortical cells, induced a slight but not significant increase of adrenaline and noradrenaline release. Similarly, the selective cholinergic agonists muscarine and nicotine did not significantly affect catecholamine release, while muscarine mimicked the stimulatory action of acetylcholine on corticosterone secretion. This study validates the use of the perifusion model to investigate the mechanism of control of catecholamine release from frog adrenochromaffin tissue. The results presented herein indicate that, in contrast to mammals, the secretion of catecholamines from the amphibian adrenal gland is not regulated by cholinergic inputs. PMID- 8504915 TI - Interrenal function in larval Ambystoma tigrinum. III. Acid-base balance responses. AB - Larval Ambystoma tigrinum (59-199 g) were treated with the drug aminoglutethimide (6 mg/day) in order to abolish steroid hormone synthesis. Steroid deprivation prevented the increase in plasma aldosterone concentration observed in sham infused larvae during respiratory acidosis. It also blocked the normal compensatory response to respiratory acidosis of elevated plasma [HCO3-] and inhibited cutaneous Na+ transport. Aldosterone (10 micrograms/day) and, to a lesser extent, corticosterone (240 micrograms/day) restored the compensatory response. Aldosterone replacement also stimulated cutaneous Na+ transport in AG inhibited larvae. The results suggest that aldosterone, at about 1000 pg/ml, supports the compensatory ionic responses to respiratory acidosis in this species. PMID- 8504916 TI - Twenty-four hour melatonin profiles in a nocturnally migrating bird during and between migratory seasons. AB - The garden warbler Sylvia borin is a long-distance migrating bird that travels exclusively at night. During the migratory seasons caged warblers develop intense nocturnal activity which may become even more intense than that during the day. It is demonstrated that in spite of dramatic seasonal changes in the 24-h pattern of locomotor activity measured in caged garden warblers, the corresponding pattern of plasma melatonin changed only very little. As in other species melatonin levels were generally low during the day (below 50 pg/ml) and high at night (350 to 650 pg/ml). A slight reduction in the nocturnal melatonin peak (from 650 pg/ml to between 350 and 400 pg/ml) observed during the autumn and spring migratory seasons, was possibly due to an increased light perception of the birds moving around while being exposed to dim night lights. In general the results show that the 24-h plasma melatonin profiles of these birds are rather robust and that locomotor activity does not depend in a simple and direct way on plasma melatonin levels. PMID- 8504917 TI - Evidence for a new subtype of serotonin receptor in oocytes of the surf clam Spisula solidissima. AB - The neurohormone serotonin 5-hydroxytryptamine (5-HT) triggers meiotic reinitiation in prophase-arrested oocytes of Spisula solidissima (Hirai et al., J. Exp. Zool. 245, 318-321, 1988). The original pharmacological profile of this oocyte response (Krantic et al., Dev. Biol. 146, 491-498, 1991) suggested a novel 5-HT receptor subtype. The present study employed [3H]5-HT binding assays to characterize these putative receptors. Kinetics of [3H]5-HT equilibrium binding saturation revealed that vitellin-deprived oocyte plasma membranes contained a homogeneous population of 5-HT-specific binding sites with an apparent affinity of 0.21 +/- 0.03 microM and maximal binding capacity of 1.22 +/- 0.62 pmol/mg protein. Analysis of [3H]5-HT-specific binding inhibition by various 5-HT-related compounds yielded a novel pharmacological profile for these binding sites. Moreover, the efficacies of most compounds in inhibiting the specific binding upon 5-HT membrane sites correlated with their efficacies in either triggering meiotic reinitiation (for agonists) or inhibiting the 5-HT-induced oocyte response (for antagonists). Such a correlation indicates that 5-HT binding sites located in the plasma membrane represent the physiological receptors involved in transduction of the biological effects of 5-HT in Spisula solidissima oocytes. PMID- 8504918 TI - Photoperiodic adaptation to breeding at different latitudes in great tits. AB - The photoperiodic responses in testicular growth and plasma levels of LH in nonmigratory great tits from Tromso, Norway (69 degrees 40'N), Goteborg, Sweden (57 degrees 42'N), and Milano, Italy (45 degrees 26'N) were compared under the same lighting conditions. Male great tits, collected during midwinter, were transferred to Goteborg, and shifted from an 8-hr day in early January to a lighting regime in which day length was increased by 1/2 hr per week for 16 weeks. Control birds (only from Sweden) were kept on a 8L:16D light regime during the entire study. Blood samples were collected weekly, and laparotomies were performed every other week. Initially testicular size (approximately 1.6 mm) and plasma levels of LH (approximately 0.45 ng/ml) were similar among the four groups. Between 4 and 8 weeks after the onset of the experiment testes gradually, but significantly, increased to about 2 mm in length in the control group. This slow growth was also observed in the experimental groups. The control bird testes did not increase in size any further. The onset of the rapid testicular growth phase differed among the three experimental groups. In great tits from Milano it began when day length exceeded 11 hr; in birds from Tromso, when day length was greater than 12 hr; and in great tits from Goteborg, when day length was between 11 and 12 hr. Once the rapid gonadal growth phase had begun it took about 6 weeks for the testes to reach maximal size (approximately 6.8 mm) in all three populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504919 TI - In vivo effects of oLH and LHRH-analog on sex reversal and plasma sex steroid profiles in the female Monopterus albus. AB - The effects of ovine-luteinizing hormone (oLH) or a synthetic analog of luteinizing hormone-releasing hormone, Des-Gly10[S-Ala6]-LHRH ethylamide acetate salt (LHRH-A), on the female phase of the protogynous Monopterus albus were investigated, and the plasma levels of androstenedione (Ad), testosterone (T), 11 oxotestosterone (KT), 11 beta-hydroxytestosterone (OHT), 17 beta-estradiol (E2) and progesterone were determined. In the postspawning stage, oLH induced precocious sex reversal in the gonad from female to male and increased plasma levels of Ad, T, KT and OHT. However, such oLH effects in M. albus females were slight at the early prespawning stage, and no significant signs of precocious sex reversal were found either in gonadal structure or in plasma hormones as those in postspawning treatment. After LHRH-A treatment of M. albus females in both postspawning and early prespawning stages, the gonadal structure remained "female type" with no sign of proliferation of either Leydig cells or male germ cells. The plasma levels of E2 were greatly increased after the treatment. PMID- 8504920 TI - Characterization of L-thyroxine transport into hepatocytes isolated from juvenile rainbow trout (Oncorhynchus mykiss). AB - Uptake of L-thyroxine (T4) by isolated trout hepatocytes was characterized after 1-min incubation of cells in a Hanks' balanced salts medium containing glucose and [125I]T4. Centrifugation through silicone oil and glycine buffer (pH 10.5) was used to separate cells from the medium and minimize extracellular binding of T4. At a T4 concentration of 0.2 nM, 15% of hepatocyte uptake was due to nonsaturable (passive) diffusion. Saturable T4 uptake obeyed Michaelis-Menten kinetics with an apparent Kt of 0.52 microM and a Jmax of 120 pmol/min/10(6) cells at 12 degrees. T4 uptake was temperature-dependent. The activation energy was 58.0 kJ/mol between 1 and 6 degrees, and 22.7 kJ/mol between 12 and 24 degrees. T4 uptake was enhanced by increased H+ concentration over the range of 6.0-9.0 pH units and decreased sharply below pH 5.0. Dinitrophenol (1 mM) and potassium cyanide (2 mM) decreased T4 uptake to, respectively, 91 and 66% of controls, indicating a requirement for metabolic energy. The sodium ionophore monensin (10 microM) and the Na(+)-H+ exchange inhibitor amiloride (0.5 mM) reduced uptake to 81 and 74%, respectively, of controls, while preincubation with ouabain (0.5 mM) or substitution of LiCl for NaCl in the medium did not modify T4 uptake, indicating that T4 transport does not depend on the presence of external Na+. The sulfhydryl-blocking reagent p-hydroxymercuribenzoate (0.5 mM) depressed T4 uptake to 32% of controls, but N-ethylmaleimide (0.5 mM) was ineffective. Inhibitors of protein binding, bromosulphothalein (0.3 mM) and 8-anilino-1 naphthalene sulfonic acid (1 mM), both decreased T4 uptake to 32 and 36% of controls, respectively, while phloretin (0.1 mM) and 5,5'-diphenylhydantoin, specific inhibitors of carrier-mediated transport, depressed uptake to 8 and 32% of controls, respectively. 3,5,3'-triiodo-L-thyronine (T3) decreased T4 uptake with an apparent Ki of 0.19 microM, indicating that T3 and T4 may share a common transport site(s). Other structural analogues, tested at 0.37 microM, influenced uptake as follows: 3,3',5'-triiodo-L-thyronine (rT3) to 76% of control; 3,5 diiodo-L-thyronine to 57%; D-thyroxine to 93%; and 3,5,3'-triiodothyropropionic acid to 78%. L-tyrosine and L-phenylalanine (each at 0.2 mM) did not decrease T4 uptake. Colchicine (0.5 mM), an inhibitor of endocytosis, decreased T4 uptake to 75% of control when added with T4 and to 53% when added to cells 3 min prior to addition of T4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8504921 TI - Characterization and quantitation of mRNA for the inhibin alpha-subunit in the granulosa layer of the domestic hen. AB - The role of inhibin in the regulation of follicular development in nonmammalian vertebrates is not well understood. We have used a porcine cDNA probe for the alpha-subunit of inhibin to characterize and quantitate the mRNA for the inhibin alpha-subunit in the granulosa layer of the domestic hen. In Experiment 1, RNA was prepared from the large preovulatory follicles and Northern analysis showed a single main band of hybridization between the porcine inhibin alpha-subunit probe and hen granulosa mRNA at approximately 1700 bp. Slot blot analysis was used in Experiment 2 to quantitate the mRNA for the inhibin alpha-subunit in the granulosa layers of the largest (F1) to fourth largest (F4) follicles. A significant dose-response relationship was established for increasing doses of RNA but no difference in amount of mRNA for the inhibin alpha-subunit was found among these four follicle sizes. Finally, in Experiment 3, inhibin alpha-subunit mRNA in the granulosa layer of F1-F4 follicles removed 6-8 hr after ovulation was quantitated by slot blot analysis. Similar to Experiment 2, a significant linear dose relationship was established for increasing doses of RNA but no difference in concentration of inhibin alpha-subunit mRNA among follicles was observed. Our results indicate that the porcine cDNA probe for the alpha-subunit of inhibin detects chicken mRNA at a size comparable to that reported for mammalian species. In addition, no difference in concentration of mRNA for the inhibin alpha-subunit was detected among the largest preovulatory follicles. PMID- 8504922 TI - Seasonal changes in plasma concentrations of sex steroids in the salamander Hynobius nigrescens. AB - Changes in plasma concentrations of androgens, estradiol-17 beta, and progesterone were examined throughout the year in Hynobius nigrescens. The highest mean concentration of androgens (312.7 ng/ml) was found in males in the process of spermiation and having just entered the breeding pond in early spring. Plasma estradiol-17 beta concentration was at its base level in females both before and after the animals had entered the pond. Plasma progesterone concentrations were low throughout the year except during the aquatic phase in March when females possessed some ova within the coelom and many ova in the oviducts and ovisacs after the completion of ovulation. During the terrestrial phase, or nonbreeding season, plasma concentrations of androgens and estradiol-17 beta were in approximate correspondence with the development of sex accessory structures. This is the first documentation of plasma concentrations of sex steroids in hynobiid salamanders. PMID- 8504923 TI - Release of conjugated catecholamines by the adrenal medulla equivalent of the American eel, Anguilla rostrata. AB - The in vivo perfusate of the cardiovascular system of the American eel (Anguilla rostrata) contains both free and conjugated fractions of dopamine, norepinephrine, and epinephrine. In vitro perifusion revealed that conjugated catecholamines are released from the adrenal medulla equivalent. Together with similar reports on mammals, this suggests that conjugated catecholamines are phylogenetically wide-spread components of the secretory cocktail of chromaffin cells. The present findings are compatible with an "active" role of the catecholamine conjugates. PMID- 8504924 TI - Adrenalectomy and steroid replacement in a small macropodid marsupial, the quokka (Setonix brachyurus): metabolic and renal effects. AB - Contrary to previously accepted observations, the quokka (Setonix brachyurus), a small macropodid marsupial, survival bilateral adrenalectomy indefinitely if injected with appropriate doses of cortisol and aldosterone, either singly or combined. Normal behavior and plasma solute concentrations could be maintained indefinitely by daily i.m. injection of 0.2 mg cortisol acetate and 0.01 mg aldosterone/kg. Plasma glucose concentration was maintained at the control value when the supplement contained cortisol but was significantly reduced with only a mineralocorticoid. Cortisol also caused a dose-related enhancement of food intake. There was no significant effect of supplementation on plasma urea concentration. Deoxycorticosterone, with or without cortisol, caused Na+ retention but aldosterone had this effect only when combined with cortisol. Urinary K+ excretion was not significantly affected by any of these corticosteroids. Withdrawal of hormone supplements caused muscular weakness and cessation of food intake within 3-6 days, accompanied by a moderate fall in Na+ and rise in K+ concentration of blood plasma as well as instability of plasma glucose concentration with hypoglycemic episodes. Renal excretion of both Na+ and K+ exceeded intake only when food intake had declined to negligible levels. Glomerular filtration rate (GFR) and renal plasma flow (RPF) fell when corticoids were withheld, without change in inulin space. However, p-aminohippurate (PAH) space fell, as did the intercompartmental exchange parameters of both inulin and PAH. Cortisol and aldosterone or aldosterone alone restored GFR, but not RPF, to the normal range. The fractional reabsorption of K+, but not Na+, was reduced in the absence of corticoids. It is suggested that, in this species, the circulatory effects of corticoids are essential for normal tissue perfusion and their influence on renal circulation is important in the control of salt and water balance. Metabolic effects are probably mainly permissive, as in other macropodid marsupials. PMID- 8504925 TI - Binding affinities of thyroxine-binding proteins in turtle plasma. AB - Binding affinities (Ka) for thyroxine (T4) by blood plasma and purified plasma proteins from two turtles, the slider (Trachemys scripta) and snapper (Chelydra serpentina), were compared with those of a human using equilibrium dialysis. The purified T4 binding protein (TBP) from T. scripta had a high affinity that was lower by about fivefold than that of human TBG (3.2 x 10(9) vs 1.7 x 10(10) M-1). The affinity of T4 binding by TBP was similar to that determined for whole plasma from this species. T. scripta plasma stripped of TBP by affinity chromatography showed a greatly reduced Ka (2.8 x 10(5) M-1) similar to that of albumin purified from the same species (3.6 x 10(5) M-1), as well as a marked increase in free T4 (9.7%) as compared to whole turtle plasma (0.13%). The T4 binding of snapping turtle plasma (Ka = 5 x 10(5) and free T4 = 2.7%) was similar to that of the TBP stripped plasma and albumin. Binding affinities for the two turtle and human albumins were similar. Because of low concentrations of albumin in the turtle blood (estimated at ca. 10 mg/ml based on binding), TBP probably accounts for a greater proportion of T4 binding in the slider turtle than does TBG in the human; e.g., when plasma T4 and TBP are elevated in T. scripta, > 98% of bound T4 would be associated with TBP. When both TBP and T4 are depressed (e.g., as in hatchlings), free T4 may actually be higher than in conditions when total T4 is elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8504926 TI - A functional association between the 5' and 3' splice site is established in the earliest prespliceosome complex (E) in mammals. AB - The earliest detectable mammalian prespliceosome complex (E) contains the non snRNP splicing factor U2AF, U1 snRNP, and several spliceosome-associated proteins (SAPs). We show that specific complexes, designated E3' and E5', assemble independently on RNAs containing only a 3' or 5' splice site, respectively. U2AF is enriched in E3', whereas U1 snRNP is enriched in E5'. Using a highly sensitive substrate-competition assay, we show that both the 5' splice site and the pyrimidine tract at the 3' splice site are required for efficient E complex assembly on intact pre-mRNA. We conclude that the 5' and 3' splice sites are associated functionally as early as E complex by either direct or indirect interactions between U1 snRNP and U2AF. Our observations predict that E complex assembly is a major control point for establishing splice site selection in both constitutively and alternatively spliced pre-mRNAs. PMID- 8504927 TI - Multiple functional domains of human transcription factor IIB: distinct interactions with two general transcription factors and RNA polymerase II. AB - Transcription factor IIB (TFIIB) plays a pivotal role in the formation of transcription-competent initiation complexes. TFIIB was found to interact with the TATA-binding protein, the small subunit of TFIIF, and RNA polymerase II. These interactions require distinct domains in TFIIB. Using the gel mobility shift assay, it was found that the amino terminus of TFIIB was necessary for the formation of complexes containing RNA polymerase II and TFIIF, whereas the carboxy-terminal domain, which is composed of two imperfect direct repeats and includes a putative amphipathic alpha-helix, was sufficient for the formation of complexes containing the TATA-binding protein and TFIIB (DB complex). Protein protein interaction analyses demonstrate that the amphipathic alpha-helix in TFIIB is important for the interaction with the TATA-binding protein. Specific residues mapping to the carboxyl terminus of the second direct repeat were found to be crucial for the interaction of TFIIB and RNA polymerase II. The interaction with the small subunit of TFIIF was mapped to the amino terminus of TFIIB, which includes a zinc finger. PMID- 8504928 TI - Drosophila 230-kD TFIID subunit, a functional homolog of the human cell cycle gene product, negatively regulates DNA binding of the TATA box-binding subunit of TFIID. AB - A Drosophila cDNA encoding the largest TFIID subunit (p230) was isolated using a degenerate oligodeoxynucleotide probe based on an amino acid sequence of the purified protein. The entire cDNA sequence contains an open reading frame encoding a polypeptide of 2068 amino acids, corresponding to a calculated molecular mass of 232 kD. The deduced amino acid sequence showed a strong sequence similarity with the protein encoded by a human gene (CCG1) implicated in cell cycle progression through G1, suggesting that p230 may be a target for cell cycle regulatory factors. The recombinant protein expressed in Sf9 cells via a baculovirus vector interacts directly with the TATA box-binding subunit of TFIID (TFIID tau or TBP) from Drosophila, human, and yeast. Surprisingly, recombinant p230 inhibits the TATA box-binding activity and function of TFIID tau, suggesting that p230 interactions with TFIID tau, and possible modulations thereof by other factors may play an important role in TFIID function. PMID- 8504929 TI - Dimerization specificity of the leucine zipper-containing bZIP motif on DNA binding: prediction and rational design. AB - We propose an interhelical salt bridge rule to explain the dimerization specificity between the two amphipathic alpha-helices in the leucine zipper structure. Using the bZIP class of DNA-binding proteins as a model system, we predicted and designed novel dimerization partners. We predicted that ATF4, a member of the ATF/CREB family of transcription factors, would preferentially form heterodimers with IGEBP1, a member of the C/EBP superfamily. These predictions were verified using a gel mobility-shift assay. To further test the value of this interhelical salt bridge rule, we modified the bZIP protein C/EBP attempting to design molecules that would form preferentially heterodimers with C/EBP or molecules that would not interact with C/EBP. These designed molecules behaved as predicted. Therefore, we conclude that this interhelical salt bridge rule is useful in understanding the dimerization specificity of bZIP proteins. In addition, we suggest that this rule could be used to design novel "dominant negative" molecules to specifically inhibit the function of target leucine zipper proteins in vivo. PMID- 8504930 TI - Replication initiates at a confined region during DNA amplification in Sciara DNA puff II/9A. AB - Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger than 6 kb by use of the neutral/neutral 2D gel method. Neutral/alkaline 2D gel analyses support the results of the neutral/neutral 2D gels and further define within the origin region an approximately 1-kb area where the majority of replication initiates. This is the first example of an origin of replication in multicellular eukaryotes that has been mapped by 2D gels to such a small defined region. Moreover, replication can be seen by the neutral/alkaline 2D gel method to proceed bidirectionally outward from this replication origin region. These data are consistent with an onion-skin mechanism whereby multiple rounds of DNA replication initiate at a specific origin of replication for Sciara DNA puff amplification. PMID- 8504931 TI - tramtrack is a transcriptional repressor required for cell fate determination in the Drosophila eye. AB - Cell fate determination in the Drosophila eye is mediated by inductive events between neighboring cells in the eye imaginal disc. These inductive signals lead to differential gene expression necessary for the elaboration of different cell types in the compound eye. Several putative transcription factors have been identified previously that may be required for expression of genes that specify cell fate in the compound eye. Repression of inappropriate gene expression may be as important as transcriptional activation in the determination of cell fate. We report the identification of a mutation in the Drosophila tramtrack (ttk) locus that is required for cell fate determination in the compound eye. ttk is expressed as two proteins, p69 and p88, shown previously to bind to the regulatory regions of several segmentation genes. In ttk1, an allele missing the mRNA encoding p88, many ommatidia contained supernumerary R7 cells and decreased numbers of R1-R6 cells. ttk1e11, which appears to disrupt both Ttk proteins, was characterized by early embryonic arrest as well as transformation of ommatidial cells into nonommatidial cell types in mosaic flies. Consistent with previous proposals that the Ttk proteins are transcriptional repressors of segmentation genes, we detected ectopic or increased expression of the segment polarity gene engrailed in several ttk1 larval tissues. We propose that p69 is required to repress expression of genes that are incompatible with development of photoreceptor cell fates, whereas p88 appears to be required to repress genes that promote the R7 cell fate. PMID- 8504932 TI - Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. AB - The GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA 2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells. PMID- 8504933 TI - A tissue-specific enhancer confers Pit-1-dependent morphogen inducibility and autoregulation on the pit-1 gene. AB - Pit-1 is a tissue-specific POU domain factor obligatory for the appearance of three cell phenotypes in the anterior pituitary gland. Expression of the pit-1 gene requires the actions of a cell-specific 390-bp enhancer, located 10 kb 5' of the pit-1 transcription initiation site, within sequence that proves essential for effective pituitary targeting of transgene expression during murine development. The enhancer requires the concerted actions of a cell-specific cis active element, Pit-1 autoregulatory sites, and atypical morphogen response elements. Pituitary ontogeny in the Pit-1-defective Snell dwarf mouse reveals that pit-1 autoregulation is not required for initial activation or continued expression during critical phases of Pit-1 target gene activation but, subsequently, is necessary for maintenance of pit-1 gene expression following birth. A potent 1,25-dihydroxyvitamin D3-responsive enhancer element defines a physiological site in which a single nucleotide alteration in the sequence of core binding motifs modulates the spacing rules for nuclear receptor response elements. Unexpectedly, the major retinoic acid response element is absolutely dependent on Pit-1 for retinoic acid receptor function. On this DNA element, Pit 1 appears to function as a coregulator of the retinoic acid receptor, suggesting an intriguing linkage between a cell-specific transcription factor and the actions of morphogen receptors that is likely to be prototypic of mechanisms by which other cell-specific transcription factors might confer morphogen receptor responsivity during mammalian organogenesis. PMID- 8504934 TI - lin-31, a Caenorhabditis elegans HNF-3/fork head transcription factor homolog, specifies three alternative cell fates in vulval development. AB - Cell-cell signaling controls the specification of vulval cell fates in Caenorhabditis elegans. Although previous studies have identified genes that function at early steps in the signaling pathway, the late steps are not well understood. Here, we begin to characterize those late events by showing that the lin-31 gene acts near the end of the vulval signaling pathway. We show that lin 31 acts downstream of the ras homolog let-60 and that lin-31 encodes a member of the HNF-3/fork head family of DNA-binding transcription factors. lin-31 regulates how vulval precursor cells choose their fate; in lin-31 mutants, these cells do not properly choose which fate to express and therefore adopt any one of the three possible vulval cell fates in a deregulated fashion. This interesting mutant phenotype suggests mechanisms for how vulval cell fates become determined. PMID- 8504935 TI - The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway. AB - The rhomboid (rho) gene, which encodes a transmembrane protein, is a member of a small group of genes (ventrolateral genes) required for the differentiation of ventral epidermis in the Drosophila embryo. The ventrolateral genes include spitz, which encodes an EGF-like ligand, and Star. The receptor for spitz may be the gene encoding the Drosophila epidermal growth factor-receptor (Egf-r) because the phenotype resulting from partial loss of function of Egf-r is similar to that of ventrolateral group mutants. Among ventrolateral genes encoding cell-surface or secreted proteins, rho is the only member expressed in a localized pattern corresponding to cells requiring the activity of the ventrolateral pathway. In this paper we provide evidence that spatial localization of rho plays an analogous role in establishing vein pattern in the adult wing. rho is expressed in early wing disc cells likely to be wing vein primordia and later is sharply restricted to developing veins. Flies homozygous for the viable rho(ve) allele have missing veins and rho fails to be expressed in rho(ve) mutant wing discs. Ectopic expression of rho during wing development leads to the formation of extra veins. Gene dosage studies among ventrolateral genes suggest that the rho product (Rho) may facilitate Spi-EGF-R signaling, resulting in activation of RAS. We discuss models for how localized expression of Rho may amplify signaling mediated by ubiquitously distributed ligand and receptor components. PMID- 8504936 TI - A conditional sterile mutation eliminates surface components from Arabidopsis pollen and disrupts cell signaling during fertilization. AB - Plants distinguish among the pollen grains that land on the stigma, permitting only compatible pollen to fertilize egg cells. To investigate these cell-cell interactions, Arabidopsis mutations that affect pollen-pistil communication were isolated. A male-sterile mutation that disrupts pollen-pistil interactions by eliminating the extracellular pollen coat (tryphine) is described here. Stigma cells that contact the mutant pollen produce callose, a carbohydrate synthesized in response to foreign pollen. The mutant pollen fails to germinate because it does not absorb water from the stigma, yet germinates in vitro, indicating it is viable. The defect is also conditional; high humidity results in pollen hydration and successful fertilization. Analysis of mature, mutant pollen indicated that it is deficient in long-chain lipids and has none of the lipoidic tryphine normally present on its surface. Immature mutant pollen grains have aberrant tryphine that disappears during pollen development. The sterile plants also lack stem waxes, and pollen from other wax-defective (eceriferum) mutants with reduced fertility has few of the lipid droplets normally present in tryphine. These results demonstrate that tryphine is critical for pollen-stigma interactions and suggest that tryphine lipids are required for fertilization, either by directly signaling the stigma or by stabilizing other tryphine components. PMID- 8504938 TI - Organ preservation: choroidal melanoma treated by brachytherapy techniques. PMID- 8504937 TI - Coupling of poly(A) site selection and trans-splicing in Leishmania. AB - Intergenic regions of polycistronic pre-mRNAs of trypanosomatid protozoans are the sites of two processing reactions: polyadenylation of the upstream gene and trans-splicing of the capped miniexon to the downstream gene. Their close proximity and the lack of consensus motifs at poly(A) sites led us to test whether poly(A) site selection is governed by the location of the downstream splice acceptor in the DHFR-TS locus of Leishmania major. Whenever the position of the downstream splice site was altered, the poly(A) site was shifted 400-500 nucleotides upstream of the new splice site. In contrast, when the wild-type poly(A) site was eliminated, the downstream splice site was unaffected, and polyadenylation was maintained 200-500 nucleotides upstream of the splice site. In a second set of experiments, T7 RNA polymerase expressed in Leishmania was used to direct the synthesis of artificial pre-RNAs in vivo whose expression was found to require the presence of a downstream splice acceptor. We conclude that poly(A) site selection in Leishmania is specified by the position of the downstream splice acceptor and propose a scanning model for poly(A) site selection after splice site recognition. PMID- 8504939 TI - Radiation or surgery for carcinoma of the esophagus: the role of organ-conserving therapy. PMID- 8504940 TI - Treatment of low rectal cancer with conservation surgery and radiotherapy. PMID- 8504941 TI - Radiotherapy versus radical surgery for gynecologic neoplasms: carcinomas of the cervix and vulva. PMID- 8504942 TI - Conservation treatment of muscle-invasive bladder cancer using radiotherapy. PMID- 8504943 TI - Results and new directions in the definitive treatment of prostate cancer with radiotherapy. PMID- 8504944 TI - The perineal field in the external irradiation of cancer of the prostate: a modified Regato technique. First Annual del Regato Distinguished Lecture. AB - (1) 50 consecutive patients with cancer of the prostate, stages A2 through C2 received external irradiation. The whole pelvis was treated using 4-MV photons, and a prostate boost was given through the perineum using a cesium-137 teletherapy unit. (2) The treatment technique was easily duplicated daily and was well tolerated. There were no grade 2, 3 or 4 complications. (3) Local control was excellent: 96% of all cases. (4) Disease-free survival was high. (5) Potency was maintained in the majority of this elderly population. Considering that American males have an increasing longevity and thus a greater likelihood of developing cancer of the prostate, external-beam radiation therapy should be utilized in the future even more so than today. We must continue to refine radiation therapy techniques in order to further increase disease-free survival and reduce radiation morbidity. PMID- 8504945 TI - Soft tissue sarcoma: combined modality approaches. PMID- 8504946 TI - Carcinomas of the oral cavity and oropharynx. Curative treatment with preservation of function. PMID- 8504947 TI - Limb preservation for bone cancers. PMID- 8504949 TI - Cancer cure with organ preservation using radiation therapy. PMID- 8504948 TI - Advances in precision treatment: some aspects of 3D conformal radiation therapy. PMID- 8504950 TI - Carcinomas of the larynx and hypopharynx. Curative treatment with preservation of laryngeal function. PMID- 8504951 TI - Organ preservation therapy in stage T1 and T2 carcinoma of the breast. PMID- 8504952 TI - Radiotherapy-chemotherapy integration in breast-conservation therapy. PMID- 8504953 TI - Trefoil peptides and the gut. PMID- 8504954 TI - Helicobacter pylori and non-steroidal anti-inflammatory drugs: uncomfortable partners in peptic ulcer disease. PMID- 8504955 TI - Mucosal polyamine metabolism in the columnar lined oesophagus. AB - Mucosal ornithine decarboxylase activity and polyamine content has been proposed as a possible marker for malignant potential in gastrointestinal mucosa. Polyamine content and histological findings were examined in 107 pairs of endoscopic biopsy specimens taken from gastric fundus, fundic and specialised Barrett's oesophagus and Barrett's adenocarcinoma. The content of putrescine (median nmol/mg protein, range) the primary product of ornithine decarboxylase showed a progressive increase from gastric fundus (0.41, 0.15-1.5); fundic (0.45, 0.01-4.08); specialised Barrett's oesophagus (0.54, 0.01-2.0); dysplastic columnar lined oesophagus (0.56, 0.31-3.1) to adenocarcinoma (1.23, 0.29-8.98). Adenocarcinoma putrescine content was significantly greater than gastric fundus (p < 0.018) and fundic (p < 0.03). Mucosal spermine, spermidine, and total polyamine values were greater in gastric fundus than fundic, specialised Barrett's oesophagus, and dysplastic columnar lined oesophagus (all p < 0.001) suggesting failure to further metabolise putrescine to its higher polyamines in the metaplastic epithelium. Although metaplastic columnar lined oesophagus shows significant differences in polyamine metabolic activity from the stomach the important distinction between specialised and dysplastic columnar lined oesophagus cannot be made by measuring the polyamine content. PMID- 8504956 TI - Gastric mucosal barrier: evidence for Helicobacter pylori ingesting gastric surfactant and deriving protection from it. AB - Ultrastructural examination by electron microscopy has been undertaken on human oxyntic mucosa from biopsy specimens obtained during diagnostic endoscopy from patients in whom infection by Helicobacter pylori was subsequently confirmed. A novel fixation procedure was used that avoided conventional fixatives based upon glutaraldehyde, which can destroy the hydrophobic lining of surfaces such as gastric mucosa. The resulting electron micrographs show densely osmiophilic inclusions of varying sizes in Helicobacter, some of which can be resolved and identified as lamellar bodies and their partially digested states. This finding indicates that Helicobacter may act as an aggressive agent by ingesting a gastric mucosal barrier of gastric surfactant, exposing the surface to attack by acid while simultaneously rendering it less hydrophobic. There is also evidence that Helicobacter pylori avoid their own digestion by coating themselves with essentially the same barrier of gastric surfactant, probably derived from the host. This is a possible explanation for the apparent absence of these bacteria in the duodenum. PMID- 8504957 TI - 13C-urea breath test for diagnosis of experimental Helicobacter pylori infection in barrier born pigs. AB - Previous studies with Helicobacter pylori infected barrier born pigs indicate that the infection has a patchy distribution, resulting in false negative culture results on endoscopic biopsy specimens. This study aimed to adapt the 13C-urea breath test as used in humans to diagnose H pylori infection in barrier born pigs. The breath test was also performed after bismuth as a single treatment and after triple therapy (bismuth, ampicillin, metronidazole). In control pigs the median excess of 13CO2 in expired air was 2.2 (range 0-12 n = 22) ppm. The infected pigs (n = 4) showed consistently high values (median 23 range 14-43) when examined on four occasions (n = 16) four to 10 weeks after inoculation. Biopsy specimens for culture had lower sensitivity than the breath test. No reduction in excess 13CO2 was seen after three days' single bismuth treatment, but after two weeks' triple therapy the breath test results had returned to normal. This suppression was temporary only, however, as the breath test was positive again four weeks after stopping treatment. In conclusion, the 13C-urea breath test is a simple and reliable test for determining H pylori infection and monitoring treatment effects in barrier born pigs. Because the test can be performed in awake pigs anaesthesia and gastroscopy are unnecessary. PMID- 8504958 TI - Incidence of Helicobacter pylori strains activating neutrophils in patients with peptic ulcer disease. AB - A total of 61 human gastric isolates of Helicobacter pylori were studied for their ability to induce an oxidative burst in human neutrophils measured by luminol enhanced chemiluminescence. About one third of the strains induced strong and rapid chemiluminescence in neutrophils even without serum opsonins and agglutinated these cells on glass slides within two minutes. For other strains complement was required, although even then the reactions remained at a lower level. The activating and agglutinating property was bound to the cells, heat labile, and sensitive to several enzymes but resistant to acid. Strains possessing such activity were more common in patients with peptic ulcer disease than in patients with active chronic gastritis only (p = 0.0261, Fisher's exact test, two tailed). The activity shown might be a new indicator for ulcerogenic strains and could also partly explain the accumulation of neutrophils in the gastric mucosa during H pylori infection. PMID- 8504959 TI - Comparison of computed tomography, endosonography, and intraoperative assessment in TN staging of gastric carcinoma. AB - From 1986 to 1990 a prospective comparative study was undertaken to compare the relative accuracy of computed tomography, endogastric ultrasonography, and intraoperative surgical assessment in evaluating the depth of invasion (T category) and involvement of lymph nodes (N category) of patients with gastric carcinoma. One hundred and eight consecutive patients, who were treated by total gastrectomy and previously evaluated with computed tomography, endogastric ultrasonography, and intraoperative surgical assessment, entered the study. Results (T and N category) were compared with those of histopathological staging (pT and pN category). T categories were correctly staged in 43% of cases with computed tomography, 86% with endogastric ultrasonography, and 56% with intraoperative surgical assessment. Computed tomography scanning correctly staged 51% of all N1 and N2 lymph nodes compared with 74% for endogastric ultrasonography and 54% for intraoperative surgical assessment. In general, computed tomography was more accurate for advanced stages of cancer and showed a tendency to overstage the T category and understage N category of gastric tumours. By contrast, endogastric ultrasonography was equally accurate for all T categories and showed an understaging for N categories. Intraoperative surgical assessment overstaged early T stages, understaged T4 tumours, and was equally accurate for all grades of N categories. Computed tomography scanning and intraoperative surgical assessment of T and N categories were of little value in staging of gastric carcinoma. Endogastric ultrasonography is more accurate than computed tomography scanning and intraoperative surgical assessment. Therefore endogastric ultrasonography should be introduced in the preoperative assessment of patients with gastric carcinoma. PMID- 8504960 TI - Sex differences in the incidence of colorectal cancer: an exploration of oestrogen and progesterone receptors. AB - Sex differences exist in the site specific incidences of colorectal cancer. The increased incidence of colonic cancer in women with breast cancer and the protective effect of increasing parity suggest a role for sex hormones. To explore the molecular basis, the expression of messenger RNA for oestrogen and progesterone receptors in the large bowel has been studied. With northern and dot blot analyses mRNA coding for oestrogen receptor and progesterone receptor in large bowel cancers and corresponding normal mucosa and in adenomatous polyps has been identified. There were no significant differences in receptor mRNA concentrations between males and females or between cancers, normal mucosae, and polyps, except for rectal cancers, which had higher progesterone receptor concentrations than corresponding normal tissue. Oestrogen and progesterone receptor mRNA concentrations were strongly correlated in both cancers and normal tissues. Enzyme immunoassay for oestrogen receptor gave values of 1.2-7.4 fmol/mg total protein, an amount similar to that seen in normal breast tissue. Oestrogen receptor protein and mRNA for oestrogen receptor and progesterone receptor are present in the large bowel. PMID- 8504961 TI - Effect of cytokines on the epithelial function of the human colon carcinoma cell line HT29 cl 19A. AB - In various intestinal diseases, lymphoid cell infiltration of the lamina propria might be an important factor causing intestinal dysfunction through cytokine release. The effects of such cytokines were therefore measured on chloride secretion and macromolecular transport in intestinal HT29 cl 19A cells. Cells were grown on transwell filters and serosally exposed for two to 48 hours to 1% or 5% concentrations of phytohaemagglutinin (PHA) activated or non-activated healthy human mononuclear cell culture supernatants. These supernatants were tested for their interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha), and interleukin 6 (IL6) concentration. The mean (SE) were 4.72 (1.63), 3.17 (0.14), and 4.47 (1.12) ng/ml in activated supernatants. Intestinal function was studied in Ussing chambers: chloride secretion was assessed from the variations in short circuit current, and epithelial barrier capacity was monitored by the electrical resistance of the HT29 cl 19A cell monolayers and by measuring intact or degraded fluxes of the macromolecular tracer horseradish peroxidase. Release of lactate dehydrogenase (LDH) in the presence of various concentrations of cytokines was assessed as a test for cellular injury. The results indicate that serosal cytokines do not directly stimulate short circuit current. Long term (48 hours) exposure, however, significantly reduced both short circuit current (6.79 (0.65) v 2.90 (1.16) microA/cm2 in control v treated cells) and barrier capacity as shown by the decrease in resistance of the HT29 cl 19A cell monolayers from 158 (10) to 36 (9) ohms.cm2, and the increase in intact fluxes from 167 (33) in controls to 874 (206) ng/h.cm2, in cytokine rich supernatant treated cells and in degraded fluxes from 1113 (114) to 2327 (234) ng/h.cm2. This decreased barrier capacity was associated with an increase in release of LDH F(21.7 (1.2) and 43.6 (2.0) UI/h.cm2 in 1% and 5% cytokine treated monolayers v 10.8 (2.1) UI/h.cm2 in control monolayers). The results indicate that cytokines do not directly stimulate intestinal chloride secretion but that prolonged exposure to these agents reduced both electrolyte transport and barrier capacity to macromolecules through cellular and paracellular pathways. PMID- 8504962 TI - p53 expression and K-ras mutation in colorectal adenomas. AB - The frequency of p53 overexpression and K-ras codon 12 mutation was investigated in a series of colorectal adenomas. p53 was detected by immunohistochemistry in only 5% of tumours, whereas K-ras mutation was found in eight of 30 adenomas examined. In vitro, mutant p53 and ras genes cooperate to transform primary rat cells into a tumourigenic cell line. The presence of both p53 overexpression and K-ras mutation in a benign tubulovillous polyp in the present series suggests that in vivo this combination of events is insufficient to cause malignant transformation of a large bowel adenoma. PMID- 8504963 TI - The value of in vivo electrophysiological measurements for monitoring functional adaptation after massive small bowel resection in the rat. AB - The process of functional adaptation after extensive small bowel resection is complex and imprecisely understood. In vivo electrophysiological measurements for monitoring the functional adaptive process after massive small bowel resection in Brown-Norway rats were evaluated. Rats underwent either a sham operation (SH) or a 90% small bowel resection (SB). Standard rat chow was fed in unlimited quantities. At three or 10 weeks after operation, jejunal and ileal transepithelial potential differences (PD, mV) were determined. Electrogenic ion transport in the villus was measured after glucose (sodium coupled active glucose absorption; PD-glu) and in the crypt, after theophylline infusion (theophylline stimulated chloride secretion; PD-theo). Biopsies were taken simultaneously. Each experimental group consisted of three to five animals. At three weeks the PD-theo and PD-glu in SB rats were significantly lower than in SH rats in both jejunal and ileal segments. At 10 weeks PD-theo and PD-glu were significantly diminished in the jejunal segment of the SB rats compared with the SH rats. The values of PD theo and PD-glu in the ileal segments were, however, no longer different between the two groups. Three and 10 weeks after operation the length of the villi in the SB group was increased significantly compared with the SH controls. These results indicate that in the early phase of adaptation in vivo electrophysiological variables do not correlate with histological changes in the SB rats. This might be due to cell immaturity resulting from an increased rate of cell turnover or lack of intercellular tight junctions. This hypothesis is supported by a recovery of PD responses in the ileum 10 weeks after resection. PMID- 8504964 TI - Absorbed aluminium is found with two cytosolic protein fractions, other than ferritin, in the rat duodenum. AB - After in vivo perfusion of the upper intestine of the rat with a range of concentrations of aluminium chloride, entry of the metal into the portal system was only detected when the perfusate exceeded 400 mumol/l, suggesting a mucosal block. Using gel filtration of a mucosal cytosol extract, two consistently appearing aluminium peaks were identified which may represent aluminium binding proteins. Both were heat stable at 60 degrees C and had molecular sizes of about 700 (kilo daltons) (kD) and 17 kD respectively. The larger molecule was distinct from ferritin. Neither molecule associated with 59Fe nor 45Ca. It is suggested that the aluminium peaks are relatively specific aluminium binding proteins that have a scavenging role, reducing entry of the metal from the intestinal contents into the portal blood. PMID- 8504965 TI - Perioperative endoscopy of the whole small bowel in Crohn's disease. AB - The aim of this study was to search for small bowel lesions by means of a perioperative endoscopy in 20 patients operated on for Crohn's disease. Seven women and 13 men (mean age 29 years) had a total retrograde exploration to the angle of Treitz during an ileocolectomy (16 of 20 patients) or a colonic or ileal resection (four of 20 patients). Endoscopic exploration was completed, through an enterotomy, from the surgical area to the angle of Treitz. Periendoscopic biopsy samples were taken on macroscopic lesions and every 20 cm systematically. In 13 of 20 cases, various lesions scattered over the whole small intestine were found. These were aphthoid ulcerations (10 patients), superficial ulcerations (seven patients), mucosal oedema (three patients), non-ulcerative stenosis (three patients), erythema (two patients), pseudopolyps (two patients), deep ulcerations (two patients), and ulcerative stenosis (one patient). In seven patients none of the lesions detected at perioperative endoscopy had been recognised by preoperative evaluation or surgical inspection of the serosal surface. A typical granuloma was found at biopsy of lesions identified by endoscopy in three cases and at biopsy of an apparently healthy area in one case. Thus 65% of patients operated on for Crohn's disease had lesions of the small intestine detected by endoscopy, which were unrecognised before surgery in more than half of the cases. PMID- 8504966 TI - Epithelial deposits of immunoglobulin G1 and activated complement colocalise with the M(r) 40 kD putative autoantigen in ulcerative colitis. AB - The intestinal expression pattern and general tissue distribution of the M(r) 40 kD putative epithelial autoantigen in ulcerative colitis were re-examined by in situ two and three colour immunofluorescence staining including the murine monoclonal antibody 7E12H12. The intestinal distribution was also compared with the epithelial codeposition of IgG1 and activated complement (C3b and terminal complement complex) seen selectively in ulcerative colitis. The M(r) 40 kD antigen was found for the first time in goblet cells of normal terminal ileum and proximal colon but not in rectal goblet cells. By contrast, colonic enterocytes expressed this antigen apically with increasing intensity in a distal direction, expanding to intense cytoplasmic expression in rectal enterocytes. The antigen was also expressed by the epithelium of the fallopian tubes, major bile ducts, gall bladder, and epidermis but not by proximal gastrointestinal tract epithelium or 13 other extra-gastrointestinal organs. Activated complement and IgG1 often colocalised with the M, 40 kD antigen apically on the surface epithelium in active ulcerative colitis but not in Crohn's disease. Our results support the idea that an autoimmune response to this antigen, leading to complement activation mediated by IgG1, is a possible pathogenetic mechanism for epithelial damage and persistent inflammation in ulcerative colitis. PMID- 8504967 TI - Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis. AB - Ulcerative colitis (UC) is an inflammatory bowel disease of unknown aetiology. In this study, serum samples from 80 patients with UC were studied for the presence of various autoantibodies and soluble interleukin-2 receptor molecules (sIL-2Rs) in an attempt to determine the degree of activation of the immune system in this disease process. Autoantibodies detected included rheumatoid factors (in 5% of patients), antinuclear antibodies (in 51.3%), anti-Ro(SSA) (in 1.3%), anticardiolipin antibodies (IgG and/or IgM classes in 26.3%), anti-double stranded DNA (IgG or IgM classes in 45%), and antineutrophil cytoplasmic antibodies (ANCAs, in 30%). The ANCAs had a perinuclear pattern (p-ANCA) in 95.8%, without anti-myeloperoxidase activity, at least in an enzyme linked immunosorbent assay (ELISA) system. Raised concentrations of sIL-2R were found in 32.5% of patients (26/80, 18 with active and eight with inactive UC). The mean (SD) sIL-2R concentrations were significantly higher in patients with active UC (595 (219) u/ml v 406 (162) u/ml, p = 0.0001) and in patients with ANCAs (584 (177) u/ml in ANCA positive v 447 (212) u/ml in ANCA negative patients, p < 0.01). The sIL-2R concentrations were correlated with increased serum concentrations of C3c (r = 0.23, p < 0.05) or C4 (r = 0.4, p < 0.001) components of the complement system and erythrocyte sedimentation rate (ESR, r = 0.44, p = 0.0001). Platelets, ESR, and C3c were not associated with disease activity (p = 0.06, 0.33 and 0.86) whereas mean (SD) serum concentrations of C4 were higher in active disease (37.4 (11.9) mg/dl v 32.3 (10.3) mg/dl, p < 0.05). The sIL-2Rs had 53% sensitivity and 82.6% specificity for disease activity whereas platelet counts had 53% sensitivity and 58.7% specificity. To conclude, UC is accompanied by an autoimmune response that results in the production of several autoantibodies and cellular immune activation, as shown by the high sIL-2R concentration, is also present. The identification of the target antigen(s) of p ANCA would possibly act as an indicator of disease activity if this distinct subset of ANCAs can be attributed to the pathogenesis of UC. The sIL-2R concentrations seem to be a useful laboratory marker for assessing activity of the disease. PMID- 8504968 TI - Intestinal epithelial cells contribute to the enhanced generation of platelet activating factor in ulcerative colitis. AB - Generation of platelet activating factor by intestinal mucosal epithelial cells and lamina propria mononuclear cells was evaluated to elucidate the possible role of this mediator in the pathogenesis of inflammatory bowel disease. Epithelial and lamina propria mononuclear cells were isolated from surgical specimens from control, Crohn's disease, and ulcerative colitis patients. Platelet activating factor was extracted from highly purified cell preparations with 80% ethanol after stimulation with and without 0.2 uM calcium ionophore A23187 and was measured by platelet aggregation assay. Both cell types generated platelet activating factor activity and this was generally comparable for epithelial and lamina propria cells. Basal and stimulated platelet activating factor activity of epithelial and lamina propria cells from ulcerative colitis but not Crohn's disease patients was appreciably higher than that of control. Stimulation with calcium ionophore increased appreciably platelet activating factor activity in lamina propria cells from all groups. In contrast, only epithelial cells from ulcerative colitis showed an appreciable increase after calcium ionophore induction. These results suggest that epithelial cells are important contributors to intestinal platelet activating factor generation under normal and inflammatory conditions and that epithelial cells actively play a part in the pathogenesis of ulcerative colitis. PMID- 8504969 TI - Oroileal transit of slow release 5-aminosalicylic acid. AB - The predominant active anti-inflammatory moiety in chronic inflammatory bowel disease is 5-aminosalicylic acid (5-ASA). As unprotected 5-ASA is rapidly absorbed in the upper gastrointestinal tract several slow release preparations have been developed to permit passage of 5-ASA to the lower small bowel and to the colon. To investigate luminal kinetics and extent of the release of 5-ASA intraluminal concentrations and loads of this compound together with that of its main metabolite acetyl-5-aminosalicylic acid (ac-5-ASA) were studied, over 15 hours after giving the slow release preparation Salofalk at a dose of 500 mg orally together with a test meal. Plasma concentrations and urinary excretion were also measured. Six healthy volunteers swallowed an 11 lumen oroileal tube, which allowed marker perfusion, aspiration of luminal content from the duodenum, mid-jejunum, and ileum, and recording of intestinal motility. Emptying of 5-ASA into the duodenum started after emptying of the meal, together with the first phase III of interdigestive motility. Mean luminal concentrations of 5-ASA and ac 5-ASA increased continuously from duodenum (both: 15 to 30 micrograms/ml) to ileum (60 to 110 micrograms/ml and 80 to 150 micrograms/ml respectively) over three hours and decreased over the next three hours. During 10 hours after eating, 30% of the total dose passed the ileum in solution and another 10% were excreted in urine. Thus about 60% reached the colon unreleased from tablets and another 30% were in solution. The ratio of 5-ASA and ac-5-ASA in solution was about 1:1 in the duodenum and 1:1.5 to 1:2 in the more distal small intestine. The data suggest that the large quantities of intraluminal ac-5-ASA are generated in the intestinal mucosa and reach the lumen by back diffusion. The results show that most of the 5-ASA from this slow release preparation is delivered into the colon, which explains its effectiveness in ulcerative colitis. The considerable luminal concentrations already present in the distal ileum might justify therapeutic trials in Crohn's disease. PMID- 8504971 TI - An audit of restorative proctocolectomy. AB - A total of 168 restorative proctocolectomies have been performed without mortality during the past nine years. Morbidity from pelvic sepsis (12%), ileoanal stricture (15%), and pouch related fistulas (16%) have become less with increasing experience of the operation. Pouch excision, which occurred in 30% of the first 50 patients was undertaken in only 4% in the last 68 patients. Despite this, intestinal obstruction (18%) continues to complicate the operation. We have abandoned restorative proctocolectomy after failed ileorectal anastomosis in patients with slow transit constipation as half have now requested pouch excision because of poor results. Failure to identify Crohn's disease continues to influence the outcome: in 10 patients now known to have Crohn's disease six developed post operative fistulas, three have required pouch excision. Sexual impairment has occurred in three male patients (4%). Ten women had children after operation, eight uncomplicated vaginal deliveries occurred without impaired continence. Seven of nine patients over 60 years of age have had a successful outcome. Our data also indicate that the operation may be justified in distal disease if urgency is socially inconvenient. Frequency of defecation is usually less than three per 24 hours in patients with familial adenomatous polyposis but remains variable in those with ulcerative colitis. PMID- 8504970 TI - Comparison of bismuth citrate and 5-aminosalicylic acid enemas in distal ulcerative colitis: a controlled trial. AB - An enema that contained a complex of bismuth citrate and polyacrylate was compared with 5-aminosalicylic acid (5-ASA) enemas for treatment of distal ulcerative colitis. The multicentre trial involving 63 patients was randomised and double blind with enemas given over four weeks; clinical, sigmoidoscopic, and histological assessments were made. Improvements were seen in both treatment groups. Clinical remission was seen in 18 of 32 patients treated with 5-ASA and 12 of 31 patients treated with bismuth citrate-carbomer (chi 2 1.94; p = 0.16). Sigmoidoscopic remission occurred in 20 of 32 patients in the 5-ASA group and 15 of 31 patients given bismuth (chi 2 1.27; p = 0.26). Improvement of rectal biopsy histology by at least one grade was seen in 16 of 32 patients in the 5-ASA group and 14 of 31 patients with bismuth (chi 2 0.15; p = 0.70). Analysis of covariance gave no significant difference between groups, although there was a trend favouring 5-ASA. There was no evidence of bismuth accumulation during the trial. Bismuth enemas may offer a new therapeutic option in distal ulcerative colitis. PMID- 8504972 TI - The prevalence of anal sphincter defects in faecal incontinence: a prospective endosonic study. AB - Forty six patients (median age 61 years; 42 women) with faecal incontinence and 16 age and sex matched controls undergoing a restorative proctocolectomy were assessed by clinical examination, anorectal physiology, and anal endosonography. Forty patients (87%) with faecal incontinence had a sphincter defect demonstrated on anal endosonography (31 external and 21 internal anal sphincter defects). The commonest cause of faecal incontinence was obstetric trauma. This occurred in 35 women, 30 of whom exhibited a morphological defect in the anorectal sphincter complex. In 22 of these patients with a history of a perineal tear or episiotomy, 21 (95%) had a sphincter defect. Sphincter defects were commonly located at the level of the midanal canal. PMID- 8504973 TI - Congestive jejunopathy in portal hypertension. AB - Twenty six patients with portal hypertension of different aetiologies were studied for endoscopic evidence of congestive gastroduodenopathy and histological evidence of congestive gastropathy and jejunopathy. Per oral biopsies of jejunum were taken by Watson's capsule. Normal biopsy tissues obtained from the antrum (26), fundus (10), and jejunum (26) were used as controls. Endoscopy showed congestive changes in the fundus (17 cases), antrum (17), and duodenum (4). Duodenopathy correlated with changes in the antrum but not in the fundus. Histology showed an increase in the size and number of vessels in the jejunal villi ('congestive jejunopathy') in 22 patients. These correlated with histological evidence of gastropathy in the fundus but not in the antrum. The incidence of congestive jejunopathy did not correlate with the Child-Pugh score in patients with cirrhosis or with the number of sclerotherapy sessions received. Congestive jejunopathy is part of the spectrum of congestive gastroenteropathy and occurs at least as frequently as changes in the stomach and duodenum. The clinical import of these jejunal changes remains to be explained. PMID- 8504974 TI - Serum 7 alpha-hydroxy-4-cholesten-3-one concentrations in the evaluation of bile acid malabsorption in patients with diarrhoea: correlation to SeHCAT test. AB - The synthesis of bile acids is regulated by a homeostatic mechanism in which bile acids returning to the liver from the intestine inhibit their own synthesis. Serum concentrations of the bile acid intermediate 7 alpha-hydroxy-4-cholesten-3 one reflect the rate of bile acid synthesis whereas bile acid malabsorption can be determined by the SeHCAT test. This study was done to evaluate the correlation between the two tests in humans. Twenty eight patients with chronic diarrhoea were included in the study. Fasting serum was collected for the determination of 7 alpha-hydroxy-4-cholesten-3-one, and on the same day the gamma emitting bile acid analogue SeHCAT was given orally and its fractional catabolic rate assessed by repeated external counting over the upper abdomen during the next seven days. There was a highly significant positive correlation between the two tests (Rs = 0.80, p < 0.001). The results show a close relation between intestinal loss and hepatic synthesis of bile acids and imply that analysis of 7 alpha-hydroxy-4 cholesten-3-one in serum should now be evaluated as a possible convenient method for assessing bile acid malabsorption in patients with diarrhoea. PMID- 8504975 TI - Reduced cholesterol metastability of hepatic bile and its further decline in gall bladder bile in patients with cholesterol gall stones. AB - The reduced metastability of biliary cholesterol in the gall bladder bile of patients with cholesterol gall stones has been well shown. The purpose of this study was to examine the hypothesis that such a difference in metastability already exists in hepatic bile. Paired hepatic and gall bladder bile samples were collected from 10 patients with cholesterol gall stones and six patients without gall stones. Cholesterol nucleation time, biliary lipid concentration, vesicular cholesterol distribution, and biliary protein concentration were measured and compared. The nucleation time in the hepatic bile of patients with cholesterol gall stones was significantly shorter than the gall stone free patients (8.2 (7.2) v 15.7 (5.8) days, p < 0.05), and was associated with a greater concentration of biliary lipid despite the lack of a difference in the cholesterol saturation index (CSI) and total protein concentration. During the storage of bile in the gall bladder, the nucleation time became quicker in the patients with cholesterol gall stone (2.9 (1.7) days) while it was similar in the gall stone free patients (17.3 (5.7) days) compared with that of the corresponding hepatic bile. These differences were associated with a higher CSI (1.44 (0.33) v 1.13 (0.14), p < 0.05) and a greater vesicular cholesterol distribution (19.7 (11.9) v 4.4 (1.4)%, p < 0.01) in the patients with cholesterol gall stones than the gall stone free patients. The concentrations of total lipid and protein in gall bladder bile were not significantly different between the two groups. In conclusion, patients with cholesterol gall stones produce less metastable hepatic bile by the evidence of shorter nucleation time. During the storage of the bile in the gall bladder, the metastability is reduced further only in the cholesterol gall stone patients but not in the gall stone free patients. PMID- 8504977 TI - Oral submucous fibrosis--a chronic disseminated intravascular coagulation syndrome with local coagulopathy. PMID- 8504976 TI - Fate of oral enzymes in pancreatic insufficiency. AB - Oral pancreatic enzyme supplements, including those protected from gastric acidity by enteric coating, often achieve only partial correction of pancreatic steatorrhoea. To characterise the mechanisms involved in vivo, eight patients with steatorrhoea due to advanced pancreatic insufficiency and nine healthy controls were studied. Two sets of studies (small bowel intubation and five day faecal fat quantification) were randomly performed while patients were either on enteric coated pancreatin or equivalent placebo. A 260 cm long multilumen tube was used for double marker perfusion of two 20 cm segments located in the duodenum and in the ileum respectively. Luminal pH, flow, and trypsin and lipase activity outputs were measured at each segment for four hours postcibally. Placebo treated patients with pancreatic steatorrhoea had low enzyme outputs in the duodenal test segment and even lower outputs in the ileal segment. Pancreatin treatment significantly decreased steatorrhoea (p < 0.05) and increased luminal enzyme outputs (p < 0.05). The increase was much greater in the ileal than in the duodenal segment. Thus enteric coated pancreatin treatment abolished the normal gradient between postcibal duodenal and ileal lipase output. The results suggest that enteric coated pancreatin nearly corrects severe pancreatic steatorrhoea. The ingested lipase was utilised inefficiently, however, as luminal enzyme activity in the ileum was enhanced to a greater extent than in the duodenum, and consequently the absorptive potential of the small bowel was only partially utilised. PMID- 8504978 TI - Concentrations of 5-ASA and AC-5-ASA in human ileocolonic biopsy homogenates. PMID- 8504979 TI - Inflammatory bowel disease in Asians. PMID- 8504980 TI - Riedel's thyroiditis, retroperitoneal fibrosis, and sclerosing cholangitis: diseases with one pathogenesis? PMID- 8504981 TI - Non-steroidal anti-inflammatory drug-induced jejunal and colonic diaphragm disease. PMID- 8504982 TI - Is neoadjuvant chemotherapy a useful strategy for the treatment of stage IB cervix cancer? PMID- 8504983 TI - Intraperitoneal high-dose cisplatin and etoposide with systemic thiosulfate protection in second-line treatment of advanced ovarian cancer. AB - Several randomized trials of various malignancies treated with cisplatin indicate a dose-response relationship with higher MST and longer survival achieved with high-dose compared to standard dose cisplatin regimens. Thirty-five patients with stages II-IV ovarian cancer with refractory cancer at second look or recurrent disease were treated second line with intraperitoneal (ip) combination chemotherapy of high-dose cisplatin (100-200 mg/m2) plus etoposide (350 mg/m2) in 1-6 cycles. Sodium thiosulfate was given as an intravenous antidote to cisplatin. A WBC nadir < 2.0 x 10(9)/liter was registered in 39 courses and a platelet nadir < 50 x 10(9)/liter in 3 courses. Severe nephrotoxicity was observed in 2 patients. Nonhematologic and nonrenal toxicity was mild except for vomiting and nausea and alopecia. No severe neurotoxicity was observed. A total of 127 courses were administered. Total median administered dose was 960 mg and 49 mg/m2/week. Treatment was changed in 5 (14%) patients due to severe nausea and vomiting, in 4 (11%) patients due to PAC problems, and in 2 (6%) patients due to nephrotoxicity. In 4 (11%) patients the dose was reduced due to hematologic toxicity. No toxic death was recorded. Median survival time from date of diagnosis was 21.8 (mean 37.9) months and the median progression-free survival from start of ip chemotherapy was 13.7 months. For patients with MRD < or = 2 cm the MST was 18.1 months. At the closing point of this study after a median follow-up time of 16.1 (range, 4.6-55.6) months, 7 (20%) patients were alive without evidence of progression, 4 (11%) were alive with cancer, and 23 (66%) were dead of cancer and 1 (3%) was dead of intercurrent disease. PMID- 8504985 TI - Pelvic lymphadenectomy in the surgical treatment of endometrial cancer. AB - Between 1982 and 1991, 76 of 322 (24%) patients with primary endometrial adenocarcinoma and morphologic risk factors underwent surgery including systematic pelvic lymphadenectomy (LA). A mean number of 37 lymph nodes per patient was removed. The number of removed nodes did not differ with respect to mode of LA, FIGO stage, depth of myometrial invasion, and histologic subtype or grade. Twenty-seven of 76 (36%) patients had lymph node metastases; 37% of lymph node metastases were < or = 2 mm in diameter. The incidence of lymph node metastases correlated significantly with the depth of myometrial invasion but not with histologic subtype and grade. Twenty-four patients with positive nodes who had stage I disease according to the clinical classification (FIGO 1971) were upstaged to stage IIIc according to the surgical staging system (FIGO 1988). This study underlines the need for complete, systematic LA and the need for thorough histologic processing with step-serial sections for correct staging of patients with endometrial cancer. PMID- 8504984 TI - The use of recombinant human erythropoietin to prevent carboplatin-induced anemia. AB - Anemia is a frequent and potentially serious toxicity associated with the use of carboplatin, particularly when this agent is administered in the salvage setting. In an effort to evaluate a possible role for human erythropoietin (rh-E) in preventing or minimizing carboplatin-induced anemia we analyzed the impact of the agent on anemia and transfusion requirements of women with ovarian cancer who were treated on one of two nonrandomized trials employing identical second-line carboplatin-based intraperitoneal regimens, with the only difference in the regimens being the addition of rh-E (Study 1, without rh-E; Study 2, with rh-E). There was a statistically significant difference in the incidence of documented nadir hemoglobin levels of < 9 g/dl (Study 1, 60%; Study 2, 13%; P < 0.005) and < 8 g/dl (Study 1, 33%; Study 3, 6%; P < 0.05). We also observed a threefold reduction in transfusion requirements with the use of rh-E (Study 1, 23%; Study 2, 6%), but this difference was not statistically significant with the limited sample size evaluated. In this nonrandomized comparison of two identical chemotherapy programs we have demonstrated that rh-E significantly reduced the incidence and severity of anemia associated with carboplatin-based chemotherapy. A randomized trial examining the potential impact of rh-E on carboplatin-induced anemia and transfusion requirements is warranted. PMID- 8504986 TI - Salvage intraperitoneal mitoxantrone therapy of ovarian cancer: influence of increasing the volume of treatment. AB - Despite the demonstrated activity of intraperitoneal mitoxantrone in patients with small volume-platinum-refractory ovarian cancer, previous reports have revealed that many patients fail to achieve adequate distribution of the cytotoxic drug throughout the peritoneal cavity when delivered in a "standard" 2 liter treatment volume. In an effort to improve the distribution and therapeutic efficacy of intraperitoneal mitoxantrone, 22 patients with platinum-refractory ovarian cancer were treated with the drug at a dose of 10 mg/m2 given in 2 liters of normal saline followed by an additional 1-2 liters every 2 weeks for eight cycles. The surgically defined complete response rate in 17 patients evaluable for response with platinum-refractory ovarian cancer was 24%, with an overall response rate of 29%. Of 18 in which the influence of treatment volume could be examined (4 patients developed catheter failure), 12 (67%) were able to tolerate a 4-liter treatment volume for > 80% of courses, with a total of 15 patients (83%) receiving treatment with a minimum of a 3-liter treatment volume. We conclude that it is possible to safely increase the intraperitoneal treatment volume to 3-4 liters in most patients undergoing this therapeutic strategy. While the impact on therapeutic efficacy of expanding the volume employed for cytotoxic drug delivery remains to be defined, in theory this approach may optimize the opportunity for agents achieving high-intraperitoneal concentrations to produce their maximal cytotoxic effect. PMID- 8504987 TI - The proto-oncogene c-fms is overexpressed in endometrial cancer. AB - Recent studies have shown that macrophage colony-stimulating factor and its receptor c-fms protein are significantly overexpressed in endometrial and ovarian cancers. In the present study, we analyzed the steady-state levels of c-fms mRNA in benign and malignant endometrial tissues by Northern and slot blot analyses. The relative levels of c-fms mRNA were quantified by using a hybridization signal for each sample on Northern blot analysis. Slot blot analysis was used to further quantitate the relative increase in c-fms mRNA in malignant specimens compared to benign specimens. Correlation of c-fms expression in the endometrial cancers was made with traditional prognostic indicators. Secretory endometrium had low levels of c-fms mRNA, whereas the endometrial cancers had the highest levels. Proliferative and hyperplastic endometrium values were intermediate. Comparative assessment of c-fms expression in endometrial cancer relative to other prognostic factors demonstrated greater expression of c-fms in specimens from patients with abnormal DNA ploidy, high-grade lesions, and possibly extrauterine metastases. Our study confirms the overexpression of c-fms in endometrial cancer and demonstrates a positive correlation between the steady-state mRNA levels of c-fms and other select adverse prognostic indicators. PMID- 8504989 TI - Ovarian transposition in cervical cancer. AB - One hundred four premenopausal women, 42 years of age or less, with early stage carcinoma of the cervix had surgical management with ovarian retention. Eighty two had ovarian transposition performed at the time of exploration for radical hysterectomy or staging lymphadenectomy because of known or possible need for radiation therapy. Twenty-two had radical hysterectomy and retained ovaries without transposition. Three patients, all in the transposed group, were lost to follow-up. Sixteen patients died of disease; all but 1 were in the transposed group. Twenty-four transposed patients received postoperative radiation therapy; 12 of these died of disease and all became climacteric prior to death. Only 4 (17%) transposed and radiated patients have continued ovarian function. Of the 58 patients with transposition who received no radiation, 9 of 51 survivors (17.6%) had subsequent oophorectomy for management of painful ovarian cysts at from 25 to 103 months (mean 46.8 months) after treatment. Sixty-seven percent still have ovarian pain and cysts requiring medical therapy. Therefore, only 53% retained ovarian function with no problems. Of the 22 patients whose ovaries were retained but not transposed 10% became climacteric at a mean of 84 months after treatment, and 21% have continued ovary-related pain or cysts at a mean of 32 months. Thus, 71% retained ovarian function and had no problems. The difference in ovarian survival between the transposed and radiated and the nontransposed nonradiated groups was significant (P < 0.001). Only 1 patient developed metastatic disease in the ovary at 17 months and 1 had a benign cystic teratoma at 62 months after treatment. We conclude that transposition is not successful in preserving ovarian function in patients who are likely to need radiation therapy and is, therefore, not indicated. Long-term follow-up is necessary to determine rates of continued ovarian function after surgery. The rate of subsequent malignancy is low. PMID- 8504988 TI - Endometrial adenocarcinoma involving adenomyosis without true myometrial invasion is characterized by frequent preceding estrogen therapy, low histologic grades, and excellent prognosis. AB - We reviewed cases of endometrial adenocarcinoma to characterize the carcinomas that involved foci of adenomyosis in contrast to the carcinoma that invaded into the myometrium. We encountered 18 cases in which tumor involved foci of adenomyosis without myometrial invasion. There were no cancer-related deaths in these 18 cases over a minimum follow-up period of 5 years. Myometrial invasive tumor was present in 43 cases. Eight of these 43 patients died within 5 years. History of postmenopausal use of estrogen of longer than 6 months duration was obtained in 9 of the 18 patients (50%) with carcinoma confined to adenomyosis compared with 8 of the 43 (19%) with myometrial invasive carcinoma. Only 1 of the 18 cases with adenocarcinoma involving adenomyosis had architectural or nuclear grade III carcinoma compared to 12 of the 43 patients with myometrial invasive carcinoma. Adenocarcinomas involving adenomyosis were characterized by frequent preceding estrogen use, low histologic grades, and excellent prognosis. PMID- 8504990 TI - Immunohistochemical evaluation of sialosyl-Tn antigens in various ovarian carcinomas. AB - Sialosyl-Tn (S-Tn) antigen, a cancer-related antigen, was expressed in 56.3% (36 of 64 cases) of the common epithelial carcinoma tissues. This antigen was moderately to strongly expressed in 83.3% (15 of 18 cases) of the mucinous adenocarcinomas. In contrast, it was weakly expressed in 31.3% (5 of 16 cases) of the serous adenocarcinomas. Expression of this antigen in ovarian mucinous tumors of borderline malignancy was 80% (4 of 5 cases), and the staining was moderately intense. S-Tn reactivity was found in 11.5% (3 of 26 cases) of benign ovarian neoplasms. The S-Tn antigen was not found in either normal ovarian tissues or the normal vaginal squamous epithelia. We conclude that the S-Tn antigen may be useful in the histological classification of ovarian carcinomas and in the determination of the malignant potential of such lesions. Moreover, because increases in serum S-Tn antigen were often accompanied by its positive expression in tumor tissues, the S-Tn antigen appears to be a tumor marker in sera with a high specificity for ovarian carcinoma, particularly mucinous adenocarcinoma. PMID- 8504991 TI - Ovarian cancer with metastatic deposits in the cervix, vagina, or vulva preceding primary cytoreductive surgery. AB - Ovarian cancer rarely metastasizes to the uterine cervix, vagina, or vulva. Equally important is the rarity of the disease in these sites at initial presentation. In a review of 148 patients with FIGO Stage III or IV ovarian cancer, 7 patients had cervical metastatic deposits. Four were due to direct extension of the primary; the 3 patients who had truly metastatic deposits all presented with cervical cytology showing the presence of adenocarcinoma cells. All the patients with cervical metastases had associated malignant ascites, retroperitoneal lymph node involvement, and significant peritoneal carcinomatosis. Their median survival was 4.4 months. There was no significant difference in survival between the patients who had truly metastatic deposits compared with those in whom the cervical disease was due to direct extension of the ovarian cancer. One patient presented with a vaginal secondary deposit 11 months prior to definitive diagnosis, and 1 had a vulval metastasis at initial examination. The patient with the vaginal deposit is still alive with no clinically detectable disease 27 months after initial presentation, while the patient with the vulval deposit had significant distant metastases at the time of presentation and died preoperatively. PMID- 8504992 TI - Endometrial cancer in postmenopausal women with and without previous estrogen replacement treatment: comparison of clinical and histopathological characteristics. AB - Clinical and histopathological features of postmenopausal endometrial cancer were studied in 63 patients who had received exogenous estrogens previously and in 76 patients who had never been exposed to estrogens. All treatments were primarily surgical. Estrogen users were younger than nonusers (P < 0.001). Body mass index, age at menarche and menopause, parity, and blood pressure were comparable in the two groups. Prevalence of diabetes mellitus was higher in nonusers (P < 0.01). Tumor stage was earlier (P < 0.001) and the histologic grade was lower (P < 0.001) in estrogen users compared to nonusers, and the frequency of clear cell and adenosquamous carcinoma was lower in estrogen users. Myometrial invasion was less pronounced in estrogen users, independently of grade and stage (P < 0.01). Number of mitoses correlated significantly with grade and with estrogen use. Features such as squamous metaplasia and "foam" cells were not related to tumor grade or use of estrogens. The receptor content correlated inversely with grade but was not related to estrogen use. Duration of estrogen treatment was not associated with tumor stage and grade. Our findings support the theory that endometrial cancer of estrogen users may be less aggressive than cancer of nonusers. PMID- 8504993 TI - Impact of age on survival of patients with ovarian cancer. AB - In an effort to determine if there are significant differences in outcome between elderly (> or = 65 years of age) and younger (< 65 years of age) women with epithelial ovarian cancer we examined the survival of patients with this malignancy who underwent their initial surgical evaluation at the Memorial Sloan Kettering Cancer Center from January 1987-January 1991. The actuarial median overall survival for the 98 younger patients has not been reached but will exceed 4 years, compared to a median survival of 24 months for the 48 elderly patients (P < 0.0001). For individuals with advanced (stages 3-4) disease, excluding patients with tumors of low malignant potential, the median survival for the younger patient population has also not been reached and will exceed 4 years, compared to 21 months for the older population (P < 0.0001). Even in the limited number of patients with local/regional (stages 1-2) ovarian cancer, there was a statistically significant superior survival for the younger group of patients (P < 0.02). With a single exception, all deaths were believed to be due principally to disease progression, rather than to an unrelated comorbid medical event. We conclude that elderly patients with ovarian cancer experience a significantly inferior survival than younger individuals with this malignancy. Evaluation of larger populations will be required to confirm the results of this analysis and to probe for explanations for the striking survival differences we have observed. PMID- 8504994 TI - The case for conservative management of "incomplete excision" of CIN after laser conization. AB - Three hundred thirteen laser cone biopsies were performed for cervical intraepithelial neoplasia (CIN) over a 4-year period. The mean age of the patients was 39.9 years and average cytology follow-up was just under 3 years. Six patients defaulted colposcopic review and were excluded from analysis. Of the 75 cases with CIN extending to the endocervical resection margin, 9 (12%) were found to have residual disease. Only 2 (3.6%) of 56 cases with CIN extending to the ectocervical margin had residual CIN detected. In the 176 cases in which the CIN lesion was excised completely there have been no cases of residual CIN. The overall detection of residual disease was 3.6%. Further surgery in those cases with CIN extending to the resection margin is excessive. These patients should be managed conservatively with regular cytological follow-up. PMID- 8504995 TI - Clear cell epithelial ovarian cancer (mesonephroid): bad prognosis only in early stages. AB - Clear cell ovarian carcinoma accounts for 4.5% of all cases of ovarian cancer at this center; 43% of patients presented with stage I disease. Stage for stage patients with advanced disease (II-IV) did no worse than other subtypes of epithelial tumors but patients with stage I disease did significantly worse at both 5 (P < 0.05) and 10 years (P < 0.02). Young age (< 60 years), advanced stage, and the presence of vascular invasion are independently poor prognostic factors, while the presence of a predominantly (> 75%) papillary or tubulocystic morphological pattern independently predicts a better prognosis. PMID- 8504996 TI - Role of prolonged stimulation of tamoxifen therapy in the etiology of endometrial sarcomas. AB - We present the first case of heterologous mixed mesodermal tumor that developed 9 years following tamoxifen therapy in a climacteric woman with no previous pelvic irradiation and was initially treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. She continued tamoxifen therapy for 2 years, following the initial treatment, until the diagnosis of a recurrent tumor by laparotomy. The patient died of the disease 5 months subsequent to the second surgery. The association of prolonged unopposed estrogenic stimulation, with tamoxifen as a possible etiologic factor in the development of endometrial sarcomas, is discussed. PMID- 8504997 TI - An unusual evolution of the serum CA 125 level in a ovarian cancer patient. AB - The usefulness of serum CA 125 measurements in monitoring ovarian cancer has been firmly established in recent years. The CA 125 levels correlate well with tumor status, have a predictive value for second-look operations, indicate responsiveness to chemotherapy, and are a strong independent prognostic factor for survival. We report here a patient with an unusual evolution of the CA 125. The primary treatment consisted of surgery and whole-abdomen radiation followed by adjuvant alkylating agent chemotherapy. Six months after the primary treatment the normal CA 125 level increased to a pathological value during the adjuvant treatment. No tumoral progression could be documented and without changing the medication the value progressively decreased to normal values over a period of 18 months. Actually almost 5 years later the CA 125 remains normal and the patient disease free. After discussion of the different etiologic possibilities the most probably explanation seems to be a radiation-induced peritoneal inflammation. The time interval, the rapid increase, and the progressive decrease of the CA 125 level all correlate well with the histopathological appearance of chronic radiation toxicity. PMID- 8504998 TI - Lower limb ischemic venous thrombosis in patients with advanced ovarian carcinoma. AB - Three cases of lower limb, deep venous thrombosis that progressed to ischemia in patients with advanced ovarian cancer are reported. One patient developed frank gangrene of the extremity. Venous stasis, secondary to venous compression from metastatic disease, was the predisposing factor in all cases. Heparin therapy was uniformly unsuccessful in halting progression of thrombosis. Ischemic thrombosis originating from extrinsic venous compression is unlikely to respond to conventional therapy alone. Local external radiation to metastatic sites, given early and possibly in conjunction with conventional treatment methods, may achieve a clinical response by causing a reduction in tumor size and thus relief of venous compression. PMID- 8504999 TI - Gonadotropin releasing hormone (GnRH) agonist therapy for reduction of leiomyoma volume. AB - A patient with menorrhagia, dysmenorrhea, and an enlarged uterus was treated with a GnRH agonist for leiomyoma volume reduction. A laser-assisted myomectomy yielded five tumors that did not appear to be well demarcated and had a combined weight of only 30 g. Postoperative pathologic evaluation revealed leiomyosarcoma with 22 mitoses per 10 high-power fields. The 8-month delay in therapy was associated with Stage IV, grade 3 disease at diagnosis. In rare cases GnRH agonist therapy may palliate symptoms and delay definitive surgical therapy of leiomyosarcoma, resulting in more advanced disease at diagnosis. PMID- 8505000 TI - Endometrial adenocarcinoma arising in a secretory endometrium. AB - Endometrial adenocarcinoma in young women below the age of 45 years and in a functioning endometrium is rare. We present the case of a 41-year-old woman, who without clinical risk factors, was found to have a focal well-differentiated endometrial adenocarcinoma in the background of a histologically secretory endometrium. Endometrial evaluation for abnormal vaginal bleeding in a young ovulating female and thorough examination of the endometrium in its entirety in the hysterectomized uterus are reemphasized. PMID- 8505001 TI - Metastatic leiomyosarcoma of the uterus: unusual presentation of a case with late endobronchial and small bowel metastases. AB - A 56-year-old woman, 8 years after a total abdominal hysterectomy for leiomyosarcoma of the uterus, presented with simultaneous metastatic tumors to the bronchus and the small bowel. The former presented as atelectasis of a lung lobe and the latter as an ileoileal intussusception. Both lesions were resected and proved to be similar to the original tumor. The patient died of metastatic liver disease, 10 years after the hysterectomy and 2 years after resection of the metastases. PMID- 8505002 TI - Ovarian surface epithelium and human ovarian cancer. AB - Approximately 80-90% of adult ovarian cancers are assumed to originate from ovarian surface cells. The morphology of the ovarian surface epithelium changes constantly, exhibiting features such as crypts, inclusion cysts, villous processes and different forms of mullerian epithelium. The unique nature of ovarian surface features and their absence in the immediately adjacent peritoneal mesothelium suggest that local factors may play an important part in modifying the growth and morphology of the ovarian surface epithelium. Recent studies tend to emphasize oncogene activation, along with concomitant cytogenetic changes, in the development of ovarian cancer. This review focuses on the roles of exogenous and endogenous factors and ovulation in the pathogenesis of ovarian cancer. PMID- 8505003 TI - Probe-guided chorionic villus sampling. Report of a new technique. AB - This paper reports a new technique of chorionic villus sampling. A new probe has been developed to allow easier passage and manipulation of the catheter and improve visualization by ultrasound. Our initial experience with this new probe guided sampling device indicates that it simplifies the operation, and this could improve the success rate. PMID- 8505004 TI - Decreased platelet aggregation during pregnancy correlates with gestational age. AB - In vivo platelet aggregation was determined in pregnant women at different gestational ages and nonpregnant women by a modification of a method. A higher platelet count ratio (PCR) was found in pregnant women after a gestational age of 13 weeks. At 16-30 and 31-41 weeks of gestation, in vivo platelet aggregation was significantly decreased. The PCR, meaning the ratio of non-aggregated platelets to all circulating platelets, correlated significantly with gestational age. It is suggested that the decrease in in vivo aggregation measured during pregnancy reflects a summarized effect of different factors during pregnancy connected to placenta and uteroplacental vessels. PMID- 8505005 TI - Seasonal patterns in tubal pregnancy. AB - An investigation of possible seasonal patterns in ectopic tubal pregnancies was conducted. The computer data utilized were based on all ectopic pregnancies, abortions and deliveries (total pregnancies) recorded in the Department of Obstetrics and Gynecology at the Chaim Sheba Medical Center, Israel, between the years 1986 and 1989. Composite monthly cohorts of ectopic tubal pregnancies and total pregnancies were constructed for each month of the year, and the probability of an ectopic pregnancy was estimated. A statistically significant increase in the probability of conception rate resulted in ectopic pregnancies which occurred during winter and spring, especially in January to June. The probability of ectopic tubal pregnancies was low (0.50%) in September and high (1.81-1.42%) in December to January. When we studied primigravidae, the same seasonal pattern was observed. The findings of our study suggest, for the first time, that there is an association between meteorological and environmental factors, and ectopic pregnancies. These factors should be considered in the epidemiology of ectopic tubal pregnancies. PMID- 8505006 TI - Risk of damage to the cervix by dilatation for first-trimester-induced abortion by suction aspiration. AB - A fall in cervical resistance to dilatation for first-trimester-induced abortions has been observed in previous studies and considered a sign of tearing of the cervical tissue. In a study of 104 patients undergoing first-trimester abortion a fall in resistance was found in 12.5% of women in whom the cervix was dilated to 9 mm, and in 66.7% when dilatation reached 11 mm. No difference between parous and nulliparous women was found. PMID- 8505007 TI - Polynomial analysis of placental flow patterns in growth-retarded fetuses. AB - Correct interpretation of conspicuous blood flow velocity waveforms cannot rely solely on the evaluation of uteroplacental vascular Doppler flow patterns by means of angle-independent indices such as the resistance or pulsatility index. In addition to the degree of pulsatility, the waveform shape between the systolic and diastolic peak values is of considerable consequence. A subdivision of the total flow waveform into orthogonal polynomial components allows both pulsatility evaluation and notching to be registered, providing a higher sensitivity in identification of pathological vascular resistance. Accurate recording and assessment of the flow waveform is therefore an important qualitative criterion for the classification of Doppler flow patterns in pregnancies with reduced uteroplacental perfusion. PMID- 8505008 TI - Maternal hemodynamic adjustments in idiopathic fetal growth retardation. AB - The hemodynamic characteristics of 11 normotensive gravidas with idiopathic fetal growth retardation (FGR), were compared with 11 controls of similar age, parity and body size. At weeks 36-38 of gestation, plasma volume was 3,161 +/- 121 ml in controls and 2,624 +/- 95 ml in the FGR group (p < 0.003); cardiac output (CO) was 6,191 +/- 132 ml/min in controls and 5,483 +/- 186 ml/min in the FGR group (p < 0.01). Total peripheral vascular resistance (TPVR) was lower in controls than in FGR (1,031 +/- 33 vs. 1,306 +/- 62 dyn/s/cm5; p < 0.001). Birth weight was correlated with both plasma volume (r = 0.61; p < 0.01) and CO (r = 0.53; p < 0.02) and inversely correlated with TPVR (r = -0.69; p < 0.001). These results are in line with the hypothesis that a reduced plasma volume leads to a lower CO and, secondarily, to reduced uterine blood flow and FGR. PMID- 8505009 TI - Decreased levels of amniotic fluid oxytocinase activity in preeclampsia. AB - Oxytocinase (EC 3.4.11.3) activity was determined in 80 amniotic fluid samples obtained from 40 normotensive primigravidas (median age 27 years) and 40 primigravidas (median age 29 years) with pregnancies complicated by preeclampsia between 32 and 39 weeks of gestation. The enzyme activity was significantly lower in preeclampsia than in normal pregnancy with matched gestations (p < 0.01). Considering the possible involvement of vasopressin and angiotensin II in preeclampsia, it is suggested that the enzyme which degrades these pressor hormones may play a role in the pathogenesis of hypertensive pregnancy. PMID- 8505010 TI - Effect of an aromatase inhibitor in human follicular fluid on DNA synthesis of granulosa cells, theca cells, and follicles. AB - An aromatase inhibitor was identified in human follicular fluid. We sought to examine the effects of this inhibitor on granulosa cells, theca cells, a mixture of granulosa and theca cells, and follicles. Granulosa cells, theca cells, the mixture of granulosa and theca cells, and follicles were incubated with [3H] thymidine and aromatase inhibitor at 37 degrees C for 40 h in Ham F-10 medium. The radioactivities of acid-soluble fractions were counted. Aromatase inhibitor markedly inhibited the DNA synthesis of granulosa cells and follicles, but it did not inhibit the mixture of granulosa and theca cells. This suggested that aromatase inhibitor was a factor in the follicle paracrine system and acted mainly on granulosa cells. PMID- 8505012 TI - Serum ceruloplasmin, plasma copper concentration and copper to ceruloplasmin ratio in cervical carcinoma. AB - Several studies have shown that plasma/serum copper and ceruloplasmin concentrations are increased in various carcinomas. We determined serum concentrations of ceruloplasmin and plasma copper concentration to evaluate the clinical usefulness of these tests in patients with cervical carcinomas. There was a significantly higher ceruloplasmin concentration in patients with cervical carcinoma compared to healthy controls. Plasma concentrations of copper were not significantly different in the two groups of subjects. The copper to ceruloplasmin ratio was lower in cancer patients than in control subjects. There was a significant increase in the serum concentrations of ceruloplasmin with increasing FIGO stage of cancer. Copper concentration in advanced tumours (FIGO stage 3) were significantly higher compared to control subjects or FIGO 1 and 2. Copper to ceruloplasmin ratio was lower in FIGO stage 2 and 3 patients compared to stage 1 or control subjects. Ceruloplasmin can also discriminate between large tumours which are inoperable and early cervical carcinomas better than copper or copper to ceruloplasmin ratio. PMID- 8505011 TI - Comparative study of progesterone plasma levels after nasal spray and intramuscular administration of natural progesterone in menopausal women. AB - 11 mg natural progesterone (P) was administered to 20 healthy menopausal women by means of a nasal spray or intramuscular injection. Circulating P levels were calculated at various times after administration. The spray formulation yielded a CMax of 3.75 ng/ml at TMax = 60 min, the area under the curve (AUC)0-720 being 1,481.6 +/- 343. Intramuscular administration yielded a mean CMax of 4.137 ng/ml at TMax = 240 min, the AUC0-720 being 2,491.2 +/- 540. P absorption was faster through the nasal than through the intramuscular route, but intramuscular administration led to high serum levels for a much longer period. PMID- 8505013 TI - Fetal circulatory endothelin-1,2 in the midtrimester. AB - Umbilical-vein blood from eight fetuses who underwent cordocentesis for rapid karyotyping at 19-22 gestational weeks was tested for immunoreactive endothelin 1,2 by means of radioimmunoassay. Endothelin was detected in the serum of all but one of these fetuses. Levels of endothelin-1,2 ranged from 8.5 to 19.2 fmol/ml (mean 13.4 fmol/ml). We speculate that endothelin in the fetoplacental circulation may play a role in the regulation of fetal hemodynamics in utero. PMID- 8505014 TI - Strangulated herniation through a defect of the broad ligament of the uterus. AB - Among internal hernias, those through the foramen of Winslow are most commonly observed. The least frequently occurring is that through the broad ligament of the uterus. The present case presented with bowel strangulating obstruction due to a defect of the left broad ligament which could be diagnosed prior to laparotomy. The patient had no significant past history, and had symptoms of colicky pain, nausea, and vomiting. Emergency laparotomy was performed. Gangrenous ileum was resected, and a defect of the broad ligament was observed bilaterally. Past history in this case supported congenital defect of the broad ligament. PMID- 8505015 TI - Squamous cell carcinoma in situ of the endometrium as superficial extension of cervical carcinoma. AB - Squamous cell carcinomas of the endometrium, either primary or secondary extending from the cervix, are rare. We report a 52-year-old woman with squamous cell carcinoma in situ of the cervix associated with squamous cell carcinoma in situ of the endometrium. The patient had received pelvic cobalt therapy 10 years earlier. She presented to the hospital with discomfort in the lower abdomen. Examination revealed vaginal stenosis and pyometra. After cervical cytology and a biopsy showing squamous cell carcinoma in situ, a wide abdominal hysterectomy with bilateral salpingo-oophorectomy (Wertheim modification) was performed. The unusual presentation of cervical carcinoma with a history of previous radiation treatment suggests the need for performing more cytologic and histologic studies on these patients, because of the risk of developing a secondary malignancy. PMID- 8505016 TI - Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation. AB - Naturally occurring dipeptides, cholecystokinine (CCK, a tetrapeptide hormone) and the artificial sweetener aspartame were nitrosated for 10-30 min with 40 mM nitrite (pH 3.5, 37 degrees C), and the resultant products examined for mutagenicity in Salmonella typhimurium TA100. Specific mutagenicities (net revertants per mumol precursor) spanned four orders of magnitude, with CCK being the most potent precursor (4700 revertants/mumol) followed by tryptophyl tryptophan (Trp-Trp; 1000 revertants/mumol). Aspartame and glycyl-Trp (Gly-Trp) had intermediate activity (300 revertants/mumol), while Gly-Gly and methionyl methionine were only weakly mutagenic (20 and 12 revertants/mumol, respectively). The dipeptides of aspartic acid, phenylalanine and tyrosine had no detectable mutagenicity (limits of detection 0.5, 40 and 5 revertants/mumol, respectively). Kinetic studies with aspartame and Gly-Trp suggested that the mutagenic products arose primarily from nitrosation of the primary amine rather than the amide or indole group. The mutagenicities of nitrosated aspartame and Gly-Trp were higher in TA100 than in TA98, and higher without than with enzymatic activation (S-9 mix) in both strains. The time-course study of Trp-Trp nitrosation showed the production of at least two mutagens: a potent but unstable mutagenicity was seen at very short nitrosation times and a more stable but weaker effect was obtained after more than 60 min of nitrosation. Not only the absolute specific mutagenicity but also the nitrite dependence of the nitrosation reaction and the stability of the nitroso product must be taken into account in determining the risk posed by endogenous nitrosation of foods in the human stomach. Under stomach conditions, nitrosation of the side-chains of certain Trp peptides would be expected to contribute more to the endogenous burden of nitrosated products than nitrosation of aspartame or Gly peptides. PMID- 8505017 TI - Phototoxic coumarins in limes. AB - Coumarins in the rind and pulp of Persian and Key limes were quantified. In the rind of Persian limes, coumarin concentrations were in the order: limettin > bergapten > isopimpinellin > xanthotoxin > psoralen. In the rind of Key limes, psoralen and xanthotoxin were analytically absent; limettin was 10 times more concentrated than either bergapten or isopimpinellin, which were equal in concentration. Coumarin content in Persian lime pulp was in the order: isopimpinellin > limettin > bergapten > xanthotoxin > psoralen. For Key lime pulp, the concentrations of limettin, isopimpinellin and bergapten were equal; psoralen and xanthotoxin were not detected. Coumarins in lime pulp were 13 to 182 times less concentrated than those in the peel. Based on the amounts and types of coumarins, Persian limes appear to be potentially more phototoxic than Key limes. Although bergapten may be the main component of limes responsible for phytophotodermatitis, dermatological interaction assays with psoralen, bergapten, xanthotoxin and limettin should be conducted. PMID- 8505018 TI - Effect of cooked meat on micronucleus frequency. AB - The possibility that inclusion of cooked meat in the diet could elevate chromosome damage risk was investigated in mice fed either a cereal diet only or a cereal diet supplemented with mutton cooked by microwaving, pan-frying or charcoal-barbecueing. The meat was provided as a supplement to the standard cereal-based diet on an approximately one-to-one basis. Chromosome damage indices included the cytokinesis-block micronucleus assay in spleen lymphocytes, the bone marrow micronucleus assay in erythrocytes and two versions of the colonic micronucleus assay. These indices were assessed after 3 or 6 months of feeding, and under each circumstance no increment in the micronucleus frequency in any of the tissues could be detected in the groups fed cooked meat when compared with each other or with the group fed the cereal diet only. There was also no correlation between the micronucleus index in lymphocytes and body weight. These data suggest that, over the time-frame studied, inclusion of meat in the diet and the extent to which meat is cooked are unlikely to be important variables affecting the micronucleus index. PMID- 8505019 TI - Effects of soya bean flakes and liquorice root extract on enzyme induction and toxicity in B6C3F1 mice. AB - Both soya bean flakes (SBF) and liquorice root extract (LRE) have previously been reported to have anticarcinogenic properties, which have been thought to be related to an increased activity of specific enzymes responsible for the detoxification of chemical carcinogens. 30- and 90-day studies were conducted in male B6C3F1 mice to determine which, if any, of several detoxification enzymes are induced by SBF or LRE. Mice fed 8 and 25% LRE showed a variety of adverse clinical signs, poor weight gain and 30% mortality. Significant increases in liver:body weight ratios were observed in both the SBF and LRE groups. No significant treatment-related gross autopsy findings were observed in any of the SBF groups. A number of abnormalities were observed in the LRE groups, including lesions of the kidney, liver, spleen and thymus. Liver samples from the 90-day study were analysed for 7-ethoxycoumarin O-deethylase (7-ECOD), benzo[a]pyrene hydroxylase (BPH), superoxide dismutase (SOD), glutathione S-transferase (GST) and UDP-glucuronyl transferase (UDPGT) at 90 days, and at an interim 30-day autopsy. No treatment-related increases were observed for BPH or SOD. Both SBF and LRE induced modest increases in UDPGT activity. SBF induced modest increases in GST activity, but LRE decreased this activity. 7-ECOD activity was significantly increased by LRE and decreased by SBF. Samples from a 30-day study in which both LRE and SBF were administered at various dose levels were examined for UDPGT activity; all dose groups showed decreases in UDPGT activity relative to controls. The results suggest that both SBF and LRE may alter the activities of specific enzymes involved in the detoxification of chemical carcinogens; however, the combination of these two foodstuffs may not produce an additive effect in B6C3F1 mice. PMID- 8505020 TI - Absorption and accumulation of cadmium, lead and mercury from foods by rats. AB - The purpose of this study was to estimate the apparent absorbability of cadmium (Cd), lead (Pb) and mercury (Hg) from different foods by young rats when these elements occur intrinsically. The study consisted of three independent experiments. In the first experiment rats were fed a casein control diet, a corn silage diet or an activated-sludge diet. Although the amount of Cd, Pb and Hg ingested from the sludge diet was orders of magnitude higher than that from the casein or corn-silage diet, the absorption of the metals was significantly less (P < 0.02) because these were present as poorly-soluble phosphates. In the second experiment, rats were fed either a commercial fish-meal control diet or an experimental fish-meal diet, with or without the addition of sodium phytate, based on catches from metal-polluted waters. No reduction in absorption resulted from the diet containing phytate as compared with the diet without phytate. The third experiment used the radioactive tracers Cd-115m, Pb-210 and Hg-203 intrinsically incorporated individually into maturing corn ears, on which the three experimental diets were based. The liver and kidney were the main target organs for all three elements (liver: Cd 0.6%, Pb 1.4% and Hg 0.6%; kidney: Cd 0.8%, Pb 0.9% and Hg 1.3%). PMID- 8505021 TI - Neurotoxic effect of enteral aluminium. AB - Long Evans rats were treated for 90 days with water-soluble, insoluble or chelated aluminium compounds. The daily treatments given were as follows: controls, NaCl (100 mg/kg body weight) plus citric acid (30 mg/kg); AlCl3 (30 or 100 mg/kg); Al(OH)3 (100 mg/kg) plus citric acid (30 mg/kg); Al(OH)3 (300 mg/kg). Their learning ability was determined in the labyrinth test at day 90, and the choline-acetyltransferase, acetylcholinesterase activity and aluminium content of the brains were measured. Soluble and chelated aluminium compounds seriously worsened the learning ability, and the aluminium content of the brain was elevated. Acetylcholinesterase activity increased and choline-acetyltransferase activity decreased, resulting in a diminished cholinergic activity, which is a characteristic of Alzheimer's disease. PMID- 8505022 TI - Multigeneration studies on red palm oil, and on hydrogenated vegetable oil containing mahua oil. AB - Edible grade red palm oil (RPO; Elaeis guineensis) is being considered for use an an edible oil in India since it is one of the richest natural sources of carotenoids. Earlier chemical and nutritional evaluations in rats indicated no adverse effects. Multigeneration breeding studies in rats have now been carried out. Mahua oil (MO; Madhuca latifolia) is used in hydrogenated vegetable oil (HVO) for human consumption. Earlier studies on MO indicated adverse effects on the male reproductive system. Hence, a study was undertaken to evaluate the safety of HVO containing 30% MO (MO-HVO) in terms of reproductive performance. A three-generation study was conducted with groups of 12 male and 12 female Wistar/NIN/inbred albino rats fed, at 10% in the diet (20% protein), groundnut oil (controls), RPO, refined, bleached and deodorized palmolein (RBDPO), or MO HVO. Reproductive parameters including percentage conception, birth weight, litter size, weanling weight, sex ratio at birth and weaning, preweaning mortality and number of days from introduction to mating, were recorded. Behavioural and reflexological tests were conducted on preweaning animals. Adult animals were subjected to weekly observation. No significant differences were found between the RPO and MO-HVO groups in comparison with groups fed GNO or RBDPO in any of the above parameters. However, certain indications of reduced fertility were observed in the MO-HVO group in the first and third generations. The results indicate that RPO did not produce any adverse effect on reproductive performance or other toxicological parameters studied, and therefore it can be considered as safe for consumption. On the other hand, HVO containing 30% MO needs further testing with a larger number of animals. PMID- 8505023 TI - Induction of cytochrome P-450-dependent enzyme activities in cultured rat liver slices. AB - Precision-cut liver slices were prepared from male Sprague-Dawley rats with a Krumdieck tissue slicer and cultured in RPMI 1640 medium for up to 72 hr. After 48 hr, cytochrome P-450 content in the slices declined to 36% of levels present in freshly cut rat liver slices. The addition of either beta-naphthoflavone (BNF) or Aroclor 1254 (ARO) partially prevented the loss of cytochrome P-450. Culture of liver slices with phenobarbitone (PB), BNF and ARO resulted in the induction of 7-ethoxycoumarin O-deethylase, 7-benzoxyresorufin O-debenzylase and 7 ethoxyresorufin O-deethylase activities. Generally, the induction of mixed function oxidase enzymes was greater in 72- than in 48-hr cultured slices, and at the concentrations examined ARO produced a greater stimulation of enzyme activities than did either PB or BNF. These results demonstrate that rat liver slices may be maintained in culture for up to 72 hr, and that they respond in a similar manner to rat primary hepatocyte cultures to some inducers of xenobiotic metabolism. Precision-cut liver slices may therefore be a useful alternative in vitro system to hepatocyte cultures for screening compounds for effects on mixed function oxidases and for assessing species differences in response. PMID- 8505024 TI - Latex allergenic difficulties. PMID- 8505025 TI - Statement by DNA Commission of the International Society for Forensic Haemogenetics concerning the National Academy of Sciences report on DNA Technology in Forensic Science in the USA. PMID- 8505026 TI - Determination of colchicine in biological fluids by reverse-phase HPLC. Variation of colchicine levels in rats. AB - A reverse-phase HPLC method for the determination of colchicine in biological fluids is proposed. Blood, liver and kidney colchicine concentrations were determined in rats at different times following intraperitoneal (i.p.) injection of 10 mg/kg of the drug. Colchicine was extracted from the samples studied using dichloromethane at pH 8. The dry extract was redissolved in the mobile phase and analyzed with simultaneous detection at 254 and 350 nm. PMID- 8505027 TI - A study of enzymohistochemistry of cerebral cortical injury. AB - Morphologic changes and quantitative determination by enzymohistochemistry were studied during various survival times after cortical injury in 60 rats. It was found that acid phosphatase (ACP) showed regular changes with various survival times after cortical injury. The ACP content decreased from 30 min to 6 h, and began to increase after 6 h; the ACP content in the region around injury decreased over the period of 5 days to 3 weeks after; the ACP content in the injured region (region around injury and control region of injury) decreased in a linear fashion with the time. The linear correlation was very marked; one may accurately estimate the survival time with injury by the regression equation given. PMID- 8505028 TI - Ultraviolet luminescence from latent fingerprints. AB - Illumination of latent fingerprints on white paper using 266-nm radiation from a Nd:YAG laser and photographic detection of their ultraviolet fluorescence, produces images with good ridge detail. The detection rate was 69% in a survey of fingerprints from 34 people compared with only 23% using an argon-ion laser at 514 nm. Prolonged exposure to UV light decreased the inherent UV fluorescence intensity but no adverse effects were observed on subsequent treatment with 1,8 diazafluoren-9-one or ninhydrin. PMID- 8505029 TI - EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. I. Stereoselectivity and clinical evaluation. AB - The stereoselectivity, cross-reactivity and clinical performance of the EMIT d.a.u. monoclonal amphetamine(A)/methamphetamine (MA) immunoassay (EM) were evaluated. The cut-off calibrator of the assay was 1000 ng/ml S(+)MA. Analysis of drug-added urines and 72 clinical specimens demonstrated a cut-off for S(+) amphetamine of approximately 400 ng/ml. The stereoisomeric selectivity of the assay was determined in a concentration vs. response manner by adding pure S(+) or R(-)isomers of A and MA, to drug free urine. The EM assay demonstrated a high selectivity for S(+)-isomers with only one of 16 urine specimens collected following excessive use of nasal inhalers yielding a positive result. This specimen contained 6000 ng/ml R(-)MA. Five-hundred clinical urine specimens were simultaneously analyzed for A or MA by the EM and EMIT-d.a.u. polyclonal (EP) amphetamine assay with 131 positive results confirmed by GC/MS. In five specimens negative by EM while positive by EP, MA was present at concentrations below the 1000 ng/ml cut-off. Two ME false positive results were apparently caused by chlorpromazine (CPZ) metabolites. A study of other phenothiazines or their metabolites gave no false positive results. The possible cross reactivity of the EM assay was further studied for phenyl-isopropylamine analogs or drugs previously reported to react with the EP assay. The EM assay showed much less cross-reactivity than EP to all drugs tested. PMID- 8505031 TI - Myocardial lesions induced after trauma and treatment. PMID- 8505030 TI - Semi-quantitative analysis of cefaclor in human serum by capillary high performance liquid chromatography/fast atom bombardment mass spectrometry. AB - Capillary high performance liquid chromatography (HPLC) was combined with frit fast atom bombardment (FAB) mass spectrometry (MS) and a detailed procedure has been established for on-line analysis of cefaclor in human serum. The capillary column (0.3 mm i.d.) enabled the introduction of entire effluent to the frit interface for FAB-MS; and a special column switching device for injection and concentration enabled the injection of as large as a 500-microliters volume sample. These conditions gave much higher sensitivity than that of previous HPLC/MS system. Thus, low levels of cefaclor could be successfully identified in sera by its mass spectral measurements 2 h after its single oral administration of a 250-mg capsule in two subjects. PMID- 8505032 TI - Disulfiram-alcohol interaction. PMID- 8505033 TI - Time since death extrapolated from vitreous potassium. PMID- 8505034 TI - Is gastric lymphoma an infectious disease? PMID- 8505035 TI - Human health effects of agrichemical use. AB - The use of pesticides and nitrogen fertilizers in agriculture has grown dramatically over the past 30 years. Currently, approximately 600 active pesticide ingredients are used, but adequate toxicologic data are available for only approximately 100 of these. Environmental exposure of humans to agrichemicals is common and results in both acute and chronic health effects, including acute and chronic neurotoxicity (insecticides, fungicides, fumigants), lung damage (paraquat), chemical burns (anhydrous ammonia), and infant methemoglobinemia (nitrate in groundwater). A variety of cancers also have been linked to exposure to various pesticides, particularly hematopoietic cancers. Immunologic abnormalities and adverse reproductive and developmental effects due to pesticides also have been reported. The health effects associated with pesticides do not appear to be restricted to only a few chemical classes. Therefore, enhanced efforts are needed to control or eliminate human exposures wherever possible. Research also is needed to better characterize and quantitate the adverse effects of agrichemicals on human health. PMID- 8505036 TI - Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy. AB - To determine the prevalence and distribution of gastric lymphoid follicles in patients with Helicobacter pylori infection, to evaluate their relationship with gastroduodenal pathology, and to assess their evolution after eradication of H pylori, mapped gastric biopsy specimens were obtained from 20 H pylori-negative normal volunteers, 25 asymptomatic volunteers with H pylori infection and no ulcer disease, 21 duodenal ulcer patients, and 16 patients with gastric ulcer. Nine infected subjects were treated by triple therapy, and biopsy specimens were obtained at 1, 4, and 12 months posttreatment. Lymphoid follicles were counted and other histologic features were scored semiquantitatively. None of the noninfected subjects had lymphoid follicles. All subjects with H pylori had follicles, which were more numerous in the antrum than in the corpus (P < .001) and on the lesser rather than on the greater curvature (P = .003). Ulcer patients had greater numbers of follicles than asymptomatic infected volunteers (P < .05). There was no relationship between number or distribution of follicles and patients' age, sex, or other mucosal inflammatory responses (except for numbers of lymphocytes: r = .785, P < .001), intensity of H pylori infection, or intestinal metaplasia. Eradication of H pylori resulted in a slow decrease (but not in the disappearance) of lymphoid follicles in all patients. Our results indicate that the careful examination of multiple specimens will reveal lymphoid follicles in the gastric mucosa of all patients with H pylori infection. The normal stomach does not contain mucosa-associated lymphoid tissue, and this study supports the concept that H pylori may be a precursor in the development of primary gastric lymphomas. PMID- 8505037 TI - Idiopathic granulomatous appendicitis, or Crohn's disease of the appendix revisited. AB - Idiopathic granulomatous appendicitis has been categorized as primary Crohn's disease of the appendix based on its pathologic features, although the clinical course of this condition simulates acute appendicitis. In this study we report the clinical and pathologic features of 10 cases of idiopathic granulomatous appendicitis and compare the histopathology to 14 appendices inflamed by Crohn's disease. The patients comprised six women and four men with an age range of 15 to 48 years (mean, 29 years). Six patients had acute onset of right lower quadrant abdominal pain while in three patients the presentation was subacute; one patient was asymptomatic. Focal neutrophilic infiltration of crypts with crypt abscesses, mucosal erosion and ulceration, fissures, transmural lymphoid aggregates, and mural fibrosis were comparable in idiopathic granulomatous appendicitis and Crohn's disease affecting the appendix. Fistulization occurred more commonly in Crohn's disease. Idiopathic granulomatous appendicitis contained 19.7 granulomas per tissue section (range, 2.75 to 71.0) compared with 0.3 granulomas per tissue section (range, 0 to 3.0) for appendices affected by Crohn's disease. No patient with granulomatous appendicitis treated by simple appendectomy had recurrence of disease at mean follow-up of 4.5 years. Our morphologic data support the clinical contention that idiopathic granulomatous appendicitis is nosologically distinct from Crohn's disease. Ironically, the presence of numerous granulomas is the histopathologic feature distinguishing idiopathic granulomatous appendicitis from Crohn's disease. PMID- 8505038 TI - Isolated atrial amyloidosis: a clinicopathologic study indicating increased prevalence in chronic heart disease. AB - Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher (P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view. PMID- 8505039 TI - Adult rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study. AB - Twenty-seven cases of adult rhabdomyoma (ARM) of the head and neck are reported. The 20 male and seven female patients ranged in age from 33 to 80 years (median age, 60 years). Symptoms included airway obstruction and a mass within the mucosa or soft tissue. Median tumor size was 3.0 cm (range, 1.5 to 7.5 cm). Seven patients (26%) presented with multinodular tumors and one tumor was multicentric. Follow-up was available in 19 cases and ranged from 2 months to 18.5 years after diagnosis (median, 6.0 years). Lesions recurred locally in eight cases (42%) 2 to 11 years after diagnosis (median, 6 years). One recurrence was multicentric. Histologically, ARM was composed of closely packed, large polygonal cells having abundant, eosinophilic, granular, or vacuolated glycogen-rich cytoplasm with focal cross-striations. Immunohistochemical stains confirmed skeletal muscle differentiation; the majority of tumors stained for myoglobin (21 of 21 tumors), muscle-specific actin (21 of 21 tumors), and desmin (19 of 21 tumors). Focal or rare immunoreactivity for vimentin (six of 17 cases), alpha-smooth muscle actin (17 of 20 cases), S-100 protein (14 of 21 cases), and Leu-7 (10 of 20 cases) also was detected. Cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, and CD68 antigen (with KP1) were not found. The characteristic histology and immunophenotype distinguish ARM from other lesions with which it is frequently confused, including granular cell tumor, hibernoma, oncocytoma, and paraganglioma. The expression of alpha-smooth muscle actin has not been reported previously in ARM; its presence could reflect aberrant expression of smooth muscle actin in skeletal muscle or possibly be a recapitulation of early skeletal muscle embryogenesis. PMID- 8505040 TI - Atypia in breast fine-needle aspiration smears correlates poorly with the presence of a prognostically significant proliferative lesion of ductal epithelium. AB - Proliferative lesions of breast duct epithelium are associated with an increased risk of subsequent carcinoma. Fine-needle aspiration criteria for these lesions are poorly defined; most studies are retrospective and do not clearly use the classification of Page and Rogers. Suggested criteria for "atypia" include crowded, enlarged, overlapping nuclei in three-dimensional groups or sheets, loss of cohesion, occasional single cells, a homogeneous cell population, chromatin changes, and increased cellularity in older patients. Our prospective series of 1,925 aspirations included 717 breast cases, of which 25 (3.5%) were considered sufficiently atypical to possibly represent proliferative lesions, but were not suspicious for carcinoma. Fifteen patients with histologic follow-up formed the basis for this study. All had physical examinations and mammogram results consistent with fibrocystic change. Their ages ranged from 30 to 70 years (median age, 44 years). Cytologic changes of atypia were cataloged. Histologically, six cases (40%) showed prognostically significant lesions (moderate, florid, or atypical hyperplasia and one lobular carcinoma in situ). Many (60%) cytologically provocative lesions may originate in prognostically trivial lesions. At this time our limited understanding of the cytologic presentation of these lesions indicates that surgical excision is essential in all instances. Efforts to recognize and properly classify these proliferations in cytologic material should continue. PMID- 8505041 TI - Immunophenotypic evaluation of the bone marrow in non-Hodgkin's lymphoma. AB - Immunophenotypic evaluations of the bone marrow (BM) are reported on 69 aspirates from 58 patients who had non-Hodgkin's lymphoma or chronic lymphocytic leukemia involving the BM. Using flow cytometry and immunofluorescence microscopy on density gradient isolated BM mononuclear cells, the neoplasm could be identified and characterized in 59 aspirates (86%) from 49 patients (84%). Using International Working Formulation guidelines the neoplasms were classified on the basis of prior or subsequent histopathology of lymph node, spleen, skin, or other soft tissue site, or by evaluation of peripheral blood in chronic lymphocytic leukemia. In nine cases the lymphoma could not be completely classified according to International Working Formulation guidelines because only BM was available for evaluation. The neoplasm in the BM was identified and characterized immunophenotypically in all 29 cases of chronic lymphocytic leukemia/well differentiated lymphocytic lymphoma (WDLL) (100%), in 11 of 12 cases of low-grade lymphoma other than WDLL (92%), in 11 of 15 cases of intermediate-grade lymphoma (73%), and in two of four cases of high-grade lymphoma (50%). Six of the nine cases not classified by International Working Formulation guidelines could be characterized immunophenotypically. In 10 cases immunophenotypic studies revealed negative findings, although the concurrent core biopsy specimens were positive. In two cases immunophenotypic studies with positive findings accompanied a negative core biopsy specimen. A panel of immunohistochemical reagents reactive with fixative/paraffin-resistant antigens was used for a retrospective evaluation of the 69 core biopsy specimens. When compared with the immunophenotypic data obtained from the marrow aspirates these results proved to be only moderately reliable in B-lineage neoplasms and unreliable in T-cell neoplasms. Thus, immunophenotyping of aspirated marrow by flow cytometry was found to be the most reliable method for determining the antigenic profiles of BM-based lymphomas. PMID- 8505042 TI - Clinicopathologic features of late hepatic dysfunction in orthotopic liver transplants. AB - Orthotopic liver transplantation (OLT) has been used with increasing frequency as a definitive treatment for end-stage liver disease. Whereas the spectrum of pathology in the early posttransplant period is well documented, the clinicopathologic features of patients with late hepatic dysfunction are less clearly defined. In a series of 100 OLTs we identified 12 patients with progressive liver dysfunction 4 months after transplantation. Four patients succumbed rapidly to fulminant hepatitis 4 to 6 months following transplantation, three of whom had recurrent hepatitis B infection. One patient lost two successive grafts owing to hepatitis C. Liver biopsies were diagnostic for hepatitis in all cases. The outcome of the remaining eight patients with late hepatic dysfunction was grim. Their clinical courses were notable for intractable and progressive cholestasis. Five patients died and two others required retransplantation. Only one patient responded to increased immunosuppression with FK506. Ductopenia was a common feature of liver biopsies in these cases, but severe ductopenia (vanishing bile duct syndrome) was seen in the liver biopsies of only four patients. In contrast, occlusive arteriopathy and secondary ischemic changes were ubiquitous. In summary, the liver biopsy is a useful adjunct in the diagnosis of late OLT dysfunction, particularly in distinguishing recurrent viral hepatitis from chronic graft rejection. Centrilobular ischemic changes occur frequently in chronic rejection, whereas ductopenia may be difficult to document consistently. PMID- 8505043 TI - Allergic proctocolitis in infants: a prospective clinicopathologic biopsy study. AB - Allergic proctocolitis is a major cause of rectal bleeding in infants, but its clinical features and laboratory results are often nonspecific. Our previous retrospective study demonstrated that large numbers of eosinophils in colonic mucosal biopsy specimens were highly associated with cases of allergic proctocolitis. Therefore, we prospectively examined 60 colonic mucosal biopsy specimens from the same sites (4, 8, and 12 cm from the anal verge) in 20 infants with clinically confirmed allergic proctocolitis to validate this morphologic feature, to characterize its distribution, and to correlate these data with the clinical information. The patients (age range, 4 to 304 days) were fed breast milk or a variety of formulas and all presented with rectal bleeding. Sigmoidoscopic examination was abnormal in 19 cases, typically characterized by focal areas of mucosal erythema. The major histologic finding was a strikingly focal increase in the number of eosinophils in all mucosal compartments, with a predilection to aggregate in close association with lymphoid nodules. Eosinophilic infiltration varied not only between biopsies at different sites, but also within individual biopsy specimens. Only 12 of 20 patients (60%) had all three of their biopsy specimens categorized as abnormal; in the remainder, only one (four patients) or two (four patients) of the three biopsy specimens were abnormal. The average number of eosinophils per high-power field of lamina propria for all cases was 15.6. No significant correlation was identified between the number of eosinophils in the mucosa and the patient's age, length of illness, endoscopic appearance, or type of inciting formula. In summary, eosinophils appear to be an excellent marker for infantile allergic proctocolitis. Given the focal distribution of the eosinophils, multiple mucosal biopsy specimens should be obtained and several levels of each examined to confirm the diagnosis. PMID- 8505045 TI - More on formalin fixation. PMID- 8505044 TI - Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes. AB - Malignant lymphoma of the testis occurs bilaterally more often than any other tumor type. We report the case of a 62-year-old man who presented with synchronous, bilateral, testicular malignant lymphomas without clinical or radiologic evidence of extratesticular disease. The patient received no therapy other than bilateral orchiectomy and subsequently developed widespread disease 6 months later. Southern blot DNA analysis was performed on the initial orchiectomy samples for immunoglobulin (Ig) gene rearrangements. These genotypic analyses showed different clonal rearrangements in the Ig heavy chain JH region but identical clonal rearrangements in the Ig light chain C Kappa region. To our knowledge this is the first genotypic demonstration of a common clonal origin in synchronous, bilateral, testicular malignant lymphomas. We interpret these findings as molecular evidence that the patient's malignant lymphoma was already disseminated at initial presentation, although it was clinically undetectable at that time. PMID- 8505046 TI - Low-profile Ionescu-Shiley pericardial bioprosthesis failure. PMID- 8505047 TI - Hormonal manipulation in the adjuvant treatment of breast cancer. PMID- 8505048 TI - Purging of autologous bone marrow in the treatment of non-Hodgkin's lymphoma. PMID- 8505049 TI - Laparoscopic surgery in cancer treatment. PMID- 8505050 TI - Are breast prostheses safe for use in breast reconstruction? Yes. PMID- 8505051 TI - Is cyclic chemotherapy better than standard four-drug chemotherapy for Hodgkin's disease? Yes. PMID- 8505052 TI - Programmed cell death: Bcl-2. PMID- 8505053 TI - Is alternating cyclic chemotherapy better than standard four-drug chemotherapy for Hodgkin's disease? No. PMID- 8505054 TI - Fluorescence in situ hybridization in cancer diagnosis. PMID- 8505055 TI - Protein-tyrosine kinases, oncogenes, and cancer. PMID- 8505056 TI - Genetic basis of renal cell cancer. PMID- 8505057 TI - The role of cytokines in radiation oncology. AB - Cytokine induction following ionizing radiation exposure occurs through transcriptional activation in specific proteins studied to date. This process can be blocked by inhibition of radiation-induced signaling pathways, which may potentially modify certain deleterious effects of radiotherapy, e.g., effects related to production of TNF or TGF-beta. bFGF is another radiation-inducible protein that may participate in repair and protection of irradiated endothelial cells following a complex interaction with cellular receptors. The cytokines such as IL-6, TNF, and IL-1 may be useful to protect hematopoietic cells from radiation, while TNF may enhance the killing of tumor cells. Our understanding of cytokine/radiation interactions is only beginning to be understood, but knowledge of the biology of these interactions may prove clinically useful. PMID- 8505058 TI - Immunohistological characterization of the cellular immune response against Yersinia enterocolitica in mice: evidence for the involvement of T lymphocytes. AB - Previous work from this laboratory has demonstrated that cloned T lymphocytes from spleens of Yersinia-infected mice can transfer immunity against Y. enterocolitica into naive animals. In this study, we investigated the cellular immune response to parenteral infection of Yersinia-resistant C57 BL/6 mice with the highly virulent Y. enterocolitica strain WA of serotype O:8 employing immunohistological methods. In the course of the infection the spleen and the liver were the organs most extensively affected. Histologically, three different patterns of inflammatory reactions could be observed: (i) small non-pyogenic granuloma-like lesions (in the liver only), (ii) microabscesses lacking a sharp outline, and (iii) larger abscesses disclosing a distinct cellular border (spleen and liver). Immunohistologically, Y. enterocolitica was detectable within abscesses but not in the small granuloma-like lesions present in the liver. CD11b/18 positive cells (= Mac-1-antigen expressed on macrophages, monocytes, granulocytes and NK-cells) could be shown in Yersinia-induced lesions. The number of these cells correlated with the extent of tissue alterations induced by Y. enterocolitica. More strikingly, we were able to demonstrate for the first time that both CD4 (helper) and CD8 (cytotoxic) T lymphocytes are present in Yersinia induced lesions. In summary, we could demonstrate for the first time that granuloma-like lesions can be induced by Y. enterocolitica. Moreover, we supported our recent study suggesting that T lymphocytes are probably involved in the immune response against Y. enterocolitica in mice. PMID- 8505059 TI - HLA Class II nucleotide sequences, 1992. AB - The HLA Class II sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2) and Nomenclature for factors of the HLA system, 1989 (3). Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by an asterisk (*). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 8505060 TI - Nomenclature for factors of the HLA system, 1991. PMID- 8505061 TI - HLA Class I nucleotide sequences, 1992. AB - The HLA Class I sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2) and factors of the HLA system, 1989 (3). Due to the increased number of sequences we have only included sequences for exons 2, 3 and 4 in this compilation. Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between nucleotides is indicated by a hyphen (-). An unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. A number of sequences that do not appear in the last Nomenclature report are given in the sequence alignment. The HLA allele and the submitting authors are the following; -BeWo C.1 (S. Ellis); Cl.10, Cl.9 (L. Cianetti), Cw6W (E. Weiss); A*68012, B*5104, Cw*0803 (P. Parham); B*4802, B*52012, B*3903, C*X (D. Watkins); B*39013 (M. Takiguchi). Full information regarding these sequences will be given in the next Nomenclature report. In addition, the B*2705W allele shown in this sequence alignment and reported by the group of E. Weiss was found to differ by 3 silent substitutions from the B*2705 (that appeared in the last published alignment). Differences are the following: B*2705: position 245 (Exon 3) 'T'; position 71 (Exon 4) 'A'; position 161 (Exon 4) 'G'. B*2705W: position 245 (Exon 3) 'G'; position 71 (Exon 4) 'G'; position 161 (Exon 4) 'A'. PMID- 8505062 TI - Nonhuman primate Mhc-DRB sequences: a compilation. PMID- 8505063 TI - A cluster type organization of the loci of the immunoglobulin light chain in Atlantic cod (Gadus morhua L.) and rainbow trout (Oncorhynchus mykiss Walbaum) indicated by nucleotide sequences of cDNAs and hybridization analysis. AB - Antibody screening and colony hybridization of cDNA libraries have been used to isolate clones of the immunoglobulin light (IgL) chain from Atlantic cod (Gadus morhua L.) and rainbow trout (Oncorhynchus mykiss Walbaum). Sequence analysis shows dissimilarities in the constant part of the molecule (CL) within each species. Comparisons of the amino acid sequences of the constant parts of the IgL chains show a 55% identity between the two teleost species. When compared with other species the highest similarities are found to the constant domain of the IgL chain from mammals (30%-37%), but the teleost IgL chain can be classified neither as kappa nor lambda. The VL domain in Atlantic cod and rainbow trout is also more similar to those of mammals than to those of other animal species, but no difference between kappa and lambda was noticed. Genomic Southern blots hybridized with fragments coding for the constant part of IgL gave several bands larger than 2 kilobases and a similar pattern was obtained with fragments coding for the variable part. These results show that the locus of the IgL chain has a multiple organization in teleost fish and that the locus has an organization similar to that of sharks. Several of the cDNA clones isolated from both the head kidney and the spleen represent nonrearranged or nonspliced mRNA, and northern blot analysis shows that such transcripts are present in both the head kidney and the spleen. PMID- 8505064 TI - Mhc-DRB genes of platyrrhine primates. AB - The two infraorders of anthropoid primates, Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys and the hominoids) are estimated to have diverged from a common ancestor 37 million years ago. The major histocompatibility complex class II DRB gene and haplotype polymorphism of the Catarrhini has been characterized in several recent studies. The present study was undertaken to obtain information on the DRB polymorphism of the Platyrrhini. Fifty-five complete exon 2 DRB sequences were obtained from six species of Platyrrhini representing both the Callitrichidae and the Cebidae families. Combined with the results of a parallel contig mapping study, our data indicate that at least three loci (DRB1*03, DRB3, and DRB5) are shared by the Catarrhini and the Platyrrhini. However, the three loci are occupied by functional genes in the former infraorder and mostly by pseudogenes in the latter. Instead of the pseudogenes, the Platyrrhini have evolved a new set of apparently functional genes-DRB11 and DRB*W12 through DRB*W19, which have thus far not been found in the Catarrhini. The DRB*W13, *W14, *W15, *W17, *W18, and *W19 genes seem to be restricted to the Cebidae family, whereas the DRB*W16 locus has so far been documented in the Callitrichidae family only. The DRB alleles of the cotton-top tamarin, and perhaps also those of the common marmoset (both members of the family Callitrichidae), are characterized by low nucleotide diversity, possibly indicating that they diverged from a common ancestral gene relatively recently. PMID- 8505065 TI - Exon-intron organization of fish major histocompatibility complex class II B genes. AB - Major histocompatibility complex (Mhc) molecules bind self and foreign peptides and present them to lymphocytes for recognition. Activation of lymphocytes by Mhc bound foreign peptides leads to specific immune response against parasites. The Mhc genes have been studied extensively in mammals and birds but much less in other vertebrate classes. In this communication we provide the first description of the exon-intron organization of class II beta-chain-encoding genes from the teleost fish Aulonocara hansbaenschi, family Cichlidae. Each of the genes consists of six exons, E1 through E6, encoding the leader peptide (E1), beta 1 domain (E1+E2), beta 2 domain (E3+E4), connecting peptide (E5), transmembrane region (E5), cytoplasmic domain (E5+E6), and the 3' untranslated region (E6). The exons are separated by relatively short introns, the length of the longest intron being 1.3 kilobase pairs. An important difference between these and all other known class II B genes is that the beta 2 domain-encoding exon is split by an intron 97 base pairs in length. The intron is absent in other teleost fishes such as Brachydanio rerio. A change in the 3' splice site of intron 4 in some of the genes of A. hansbaenschi and of another cichlid fish, Cyphotilapia frontosa, has produced two extra codons at the 5' end of exon 5. Comparison of the A. hansbaenschi coding sequences with those of C. frontosa has revealed a concentration of variability in exon 2 and part of exon 3. Taken together, these observations provide evidence for the existence in cichlid fishes of at least two class II B loci which are functionally equivalent to the corresponding loci in mammals. The exon-intron organization and sequence similarities indicate that the two loci arose by duplication from a common ancestral gene. PMID- 8505066 TI - Two more chimpanzee Patr-A locus alleles related to the HLA-A1/A3/A11 family. PMID- 8505067 TI - Nucleotide sequences of an antiidiotypic antibody from a transplant recipient. PMID- 8505068 TI - Modulatory effects of plasma and serum on T lymphocyte activation: distinctive patterns for different mitogens. AB - Published reports have shown that fresh plasma, but not cryoprecipitate-depleted plasma or fresh serum, inhibits T cell activation by phytohemagglutinin (PHA). We sought to determine if this pattern of inhibition also characterized T cell responses to mitogens differing from PHA with regard to the cell surface molecules utilized for signal transduction. The activation system included colchicine, which limits the cells to one round of division, masking stimulatory factors that enhance proliferation by boosting the number of divisions per culture period. A distinctive modulatory pattern characterized T cell responses to each of 4 mitogens tested (PHA, anti-CD3 monoclonal antibody, desialyzed oxidized erythrocytes (DOE), pokeweed mitogen). Enhanced proliferative responses to anti-CD3 and DOE were observed in the presence of serum, and reflected an increased percentage of T cells expressing CD25. These findings suggest that concerns regarding a negative impact of plasma components on T cell responsiveness, when based on results from PHA-induced activations systems, may be unwarranted. PMID- 8505069 TI - Potassium cyanide protects Escherichia coli from complement killing by the inhibition of C3 convertase activity. AB - The exact mechanism by which deposited C5b-9 complexes kill Gram-negative bacteria is unclear. It has been proposed that during complement activation the membrane attack complex triggers an energy dependent process in Gram-negative bacteria that mediates destruction of the inner membrane. This observation in part resulted from the survival of Gram-negative bacteria that were incubated with an uncoupler (DNP) or an inhibitor (KCN) of oxidative phosphorylation during complement activation. In a reexamination of this issue we employed potassium cyanide (KCN) to block energy dependent pathways and observed a dose dependent inhibition of C9 uptake on E. coli J5 during serum incubation, suggesting that cyanide was interfering with complement activation. To verify the effect on complement activation we chose specifically to study the effects of KCN on the C3 convertase of the classical pathway. Sensitized sheep erythrocytes were employed as our model system. This system allowed us to construct a series of stable intermediates that were used to test the effect of cyanide on the formation and activity of precursors of the classical pathway C3 convertase. The data illustrate that the concentrations of potassium cyanide that inhibit complement killing of J5 also inhibit C3 convertase activity on sensitized sheep erythrocytes. The results of this study refute the principal observation made by other investigators, that potassium cyanide protects bacteria from complement killing by inhibiting bacterial energy dependent pathways that spark inner membrane destruction. A better scenario is that the organisms survive because cyanide inhibits complement activation. PMID- 8505070 TI - The adjuvant effect of silicone-gel on antibody formation in rats. AB - The extent of immunological adjuvancy of silicone-gel, from mammary implants, up to now, has not been determined definitively. This study compares the immune potentiation effects of silicone-gel with that of Freund's adjuvant, using bovine serum albumin (BSA) as the test antigen in rats. Sixty, 250 gr., male Sprague Dawley rats were divided into six groups: I- phosphate buffered saline (PBS) only, II- silicone oil (Dow Corning Medical Grade 360 liquid silicone), III- 50% silicone-gel (McGhan Medical Corp.- mammary implant) in silicone oil, IV- complete Freund's adjuvant (CFA), V- incomplete Freund's adjuvant (IFA), and VI- 50% silicone oil in IFA. Each adjuvant was mixed or emulsified with an equal volume of 50 micrograms of BSA in 150 microliters of PBS. Each immunization was given intramuscularly in a single injection. Cardiac puncture test bleeds were taken at 12, 22, 40 and 56 days post immunization and the serum anti-BSA-antibody was measured by ELISA. The results indicate that silicone-gel is a potent immunological adjuvant, compared to both CFA and IFA. Silicone oil alone is not as potent as adjuvant and seems to inhibit the immune response when mixed with IFA. There thus appears to be a distinct possibility that silicone-gel may also be able to mediate an auto-immune reaction. PMID- 8505071 TI - Immunogenetics of psoriatic arthritis. PMID- 8505072 TI - HLA class I antigen serves as a receptor for human coronavirus OC43. AB - Human coronaviruses are associated with acute respiratory and enteric disease in man as such their target cells are probably the epithelial cells lining the respiratory and enteric tract. Attachment of virus to specific receptors on the cell surface is a major determinant of virus tropism in pathogenesis (1). Recently, aminopeptidase-N was identified as a cell receptor for the 229e coronavirus (2). Cell receptor(s) for OC43 coronavirus have not been identified. However, it is of pathologic significance that OC43 virus shares DNA sequence homology with the two coronavirus isolates, SK and SD, from the brain of patients with multiple sclerosis (MS) (3). Probing MS and control brain with probes specific for human, murine, porcine and bovine coronavirus by in situ hybridization resulted in the detection of coronavirus RNA in 12 of 22 MS brain samples; five of which were positive with the OC43 probe (4). A study of virus ligand interactions of OC43 with human rhabdomyosarcoma (RD) cells, which are highly susceptible to virus infection, was undertaken to identify possible cell receptors. The binding of virus collected from the supernatant of infected cells to cell proteins immobilized on nitrocellulose paper was used to screen for virus ligand interactions. The next step was the identification or development of antibodies to each of the ligands, and to test their ability to blockade receptor activity by culturing infected cells in medium containing the ligand antibodies and measuring the effect on virus yield. The preliminary experiments reported here reveal an interesting observation of strong affinity of OC43 virus for the HLA class I antigen. PMID- 8505073 TI - The detection of HIV-2 infection in southern India. AB - To determine the prevalence of HIV-2 infection in southern India, we tested two sets of sera, selected from among the samples which had been collected between January 1988 and October 1990 from high risk subjects and tested for HIV-1 antibody. They were screened for HIV-2 antibody by ELISA and repeatedly reactive sera confirmed by HIV-2 Western blot and line immunoassay. In the first set of 604 sera, only one (0.16%) was positive for HIV-2. In the second set of 24 sera, selected on the basis of having indeterminate HIV-1 Western blot profiles, again one (4%) was positive for HIV-2. The two HIV-2 infected subjects were residents of Madras or Visakhapatnam. Residents of Vellore region constituted 88 and 75 per cent of the two sets of subjects; none was positive for HIV-2. Our results show the prevalence of HIV-2 in the port-cities of southern India. Since it will spread to other regions continuous monitoring for this infection is essential in order to determine when to establish HIV-2 screening in addition to the existing HIV-1 screening of donor blood for transfusion. PMID- 8505074 TI - Serological response to Japanese encephalitis vaccine in a group of school children in South Arcot district of Tamil Nadu. AB - A trial with Biken Japanese encephalitis (JE) vaccine made in Japan was carried out in South Arcot district of Tamil Nadu state, India. A total of 113 school children were included in the trial. The efficacy (as determined by serological response) and safety of the vaccine were evaluated. Side effects, though minor, were noted in 54.9 per cent of the children after each dose. The serum antibody titres were determined by mouse neutralization test, plaque reduction neutralization test and haemagglutination inhibition test. An antibody response to two-dose primary vaccination schedule was observed in 72.7 per cent, whereas 87.8 per cent of the vaccines responded positively after the booster dose administered one year after. Only about 20 per cent of the children had persisting antibodies one year after the primary vaccination. The results indicated a probable need of the third dose in the primary vaccination schedule. PMID- 8505075 TI - Prevalence of copper resistant salmonellae in India. AB - Sixty eight of 330 strains of Salmonella belonging to three different serotypes, S. typhi, S. typhimurium and S. bareilly, referred to at the National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, between 1989-1991 were found to be copper resistant. Maximum number of strains (39.1%) were resistant in S. bareilly serotype, followed by S. typhimurium (21.7%) and least in S. typhi (17.4%). Of the 15 States/Union Territories (UTs) from where Salmonella strains were received, copper resistance was observed in strains from 10 States/UTs. This resistance was maximum among the strains from Goa (85.7%). PMID- 8505076 TI - Coagglutination test for detection of heat labile enterotoxin producing Escherichia coli strains. AB - A simple particle immunoassay based on the coagglutination (CoA) of Staphylococcus aureus strain Cowan 1 coated with heat labile enterotoxin (LT) specific antibodies was evaluated to detect LT in the cell lysates of blood agar grown Esch. coli. Among strains of Esch. coli isolated from 2661 patients with acute diarrhoea, isolates from 609 patients demonstrated LT production by CoA test. Most prevalent serogroups were 020, 078, 0128, 04, 0117, 068, 0158, 07, 0114, 0148 and 0145. A comparison of CoA with classical rabbit ileal loop and skin permeability factor assay for 100 strains showed 86, 69 and 83 LT positive strains respectively. CoA proved a more specific, simple, rapid and sensitive assay which may be useful for screening of large number of Esch. coli isolates in epidemiological investigations. PMID- 8505077 TI - Usefulness of immunoperoxidase test for serodiagnosis of genital chlamydial infections. AB - An immunoperoxidase test detecting Chlamydia trachomatis specific serum IgG and IgA antibodies, was carried out to determine its efficacy in establishing chlamydial etiology in 104 clinically diagnosed patients attending a major STD Clinic in Delhi. The patients consisted of 58 with nonspecific urethritis/cervicitis (NSU/NSC), 11 with pelvic inflammatory disease (PID), 23 with primary infertility in either male or female and 12 with lymphogranuloma venereum (LGV). IgG antibodies were tested at a dilution of 1:64 and 1:128 and IgA antibodies at 1:16. Although 27.7 per cent (5 of 18) of the controls had IgG antibodies (> or = 1:128), none had IgA, showing the IgA marker as 100 per cent specific. In 80.8 per cent of all the patients, active infection was detected, 81.0 per cent in NSU/NSC, 81.8 per cent in PID, 76.9 per cent in female infertility, 80 per cent in male infertility and 83.3 per cent in LGV patients. The immunoperoxidase test was found to be an extremely simple and rapid test especially suited for laboratories where facilities are limited. PMID- 8505078 TI - Pre- & post-fumigation bacteriological surveillance of hospital environment. AB - Study of bacteria in the environment and surfaces of hospital wards revealed Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus faecalis, Acinetobacter species, coagulase negative staphylococci and Serratia marcescens to be the predominant bacterial isolates. Surface sampling following fumigation showed significant reduction in most of the isolates. Bacterial counts in the air also showed considerable decline. Fumigation under proper technical supervision showed significant reduction in bacterial count as compared to that carried out without such supervision. This study highlights that certain bacterial species are predominantly found in the hospital environment and emphasises the need for frequent supervisory monitoring of hospital wards. PMID- 8505079 TI - Isolation & immunochemical characterization of diagnostically relevant antigens of Echinococcus granulosus. AB - Two hydatid specific polypeptides with molecular masses of 8 kDa and 116 kDa have been successfully isolated from E. granulosus hydatid cyst fluid using affinity chromatography. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and western immunoblot analysis under reducing and denaturing conditions indicated the 116 kDa purified antigen to be a hetero-tetramer consisting of 45 kDa, 66 kDa, 75 kDa and 116 kDa subunits linked by disulphide bonds while the 8 kDa purified antigen was found to be a monomer polypeptide. Affinity purified 116 kDa molecule was heat-labile, sensitive to treatment with pronase, trypsin and pepsin and its immunoreactivity as assessed in enzyme linked immunosorbent assay remained unaltered on treatment with sodium metaperiodate. The affinity purified 8 kDa molecule was heat-stable, sensitive to proteolytic enzymes and also sodium metaperiodate oxidation. Lectin binding studies revealed that the 8 kDa molecule specifically bound Concanavalin A and Triticum vulgaris, and thus had varies; is directly proportional to-D-glucose and N-acetyl D-glucosamine sugar moieties. The immunoreactivity of both the antigens remained unaltered on treatment with lipase. However, biochemical estimation of total lipid content revealed the affinity purified 116 kDa antigen to contain 6.25 per cent total lipids suggesting it to be lipoproteinic in nature. The 8 kDa antigen had no detectable total lipids biochemically. All sera from patients confirmed to have hydatidosis recognised the 8 kDa and 116 kDa polypeptides. However, sera from seven subjects with other parasitic infections also recognised the 116 kDa antigen though not the 8 kDa antigen. The data suggested that the recognition of 8 kDa antigen of E. granulosus has potential for specific immunodiagnosis of hydatidosis. PMID- 8505080 TI - Antagonistic activities of mosquito larvicidal Bacillus sphaericus (Neide) against some pathogenic bacteria. AB - Mosquitocidal strains of B. sphaericus serotype H-5a5b were shown for the first time to exhibit antagonistic activities against several human pathogens especially Salmonella. These strains of B. sphaericus also exhibited high larval toxicity against several mosquitoes. PMID- 8505081 TI - Antibacterial activity of the bryozoan Electra bellula (Hincks). AB - The antibacterial activity of the extracts of bryozoan E. bellula (Hincks) was tested against ten bacterial strains by antibiotic disc diffusion method. The maximum activity was observed against Proteus vulgaris, while Klebsiella pneumoniae and Shigella flexneri were insensitive to the bryozoan. PMID- 8505082 TI - Insecticide susceptibility status of certain populations of Aedes aegypti mosquito from rural areas of Maharashtra state. AB - Ae. aegypti mosquitoes from rural areas of Maharashtra state were subjected to insecticide bio-assays. All the populations showed resistance to DDT at larval and adult stages. No resistance to deltamithrin and malathion was detected at any stage. Biochemical analysis of these mosquito populations showed that resistance to DDT was probably due to increase in the kinetics of glutathione S-transferase. PMID- 8505083 TI - Sympathoinhibitory responses to 2-methylserotonin during changes in sodium intake. AB - The vagal-mediated reflex responses elicited by the selective serotonin type 3 receptor agonist 2-methyl-serotonin were examined by administration (6.25, 12.5, 25, and 50 micrograms/kg i.v.) of 2-methylserotonin to sinoaortic-denervated rats with either intact or sectioned vagi. To study the influence of dietary sodium intake on 2-methylserotonin-induced vagal reflex responses, we performed experiments in rats fed either a high or low sodium diet. Left ventricular end diastolic pressure was significantly higher in animals on high than low salt diet. However, mean arterial pressure and heart rate were similar in high and low salt groups. In rats with intact vagi, 2-methylserotonin produced a dose dependent increase in afferent vagal nerve activity and a dose-dependent decrease in efferent renal sympathetic nerve activity, mean arterial pressure, and heart rate. The sympathoinhibitory responses of decreased efferent renal sympathetic nerve activity, mean arterial pressure, and heart rate were abolished by vagotomy and were not affected by changes in dietary sodium intake. We conclude that the sympathoinhibitory effect of 2-methylserotonin is due to stimulation of vagal afferents with inhibitory action on peripheral sympathetic nerve activity and that the sympathoinhibitory responses are unaffected by changes in dietary sodium intake. PMID- 8505084 TI - Calcitonin gene-related peptide gene expression in the spontaneously hypertensive rat. AB - Calcitonin gene-related peptide, a product of the calcitonin gene, is a potent vasodilator neuropeptide. We have demonstrated that dietary calcium deficiency decreased the neuronal (laminae I/II of the dorsal horn of the spinal cord) content of immunoreactive calcitonin gene-related peptide in the normal rat. Neuronal calcitonin gene-related peptide levels are also reduced in the spontaneously hypertensive rat, a model characterized by calcium deficiency. However, the mechanism of this reduction in neuronal calcitonin gene-related peptide could be due to decreased synthesis or increased release. To determine if neuronal calcitonin gene-related peptide messenger RNA (mRNA) levels are also decreased in the spontaneously hypertensive rat, we measured relative calcitonin gene-related peptide mRNA levels (using a genomic hybridization probe specific for alpha- and beta-calcitonin gene-related peptide mRNA) in dorsal root ganglia from spontaneously hypertensive and Wistar-Kyoto control rats. Dorsal root ganglia neuronal cell bodies are a prominent site of calcitonin gene-related peptide synthesis and send axons to peripheral blood vessels and central spinal cord sites (laminae I/II). After normalization of calcitonin gene-related peptide mRNA levels of 18S RNA, the calcitonin gene-related peptide mRNA/18S RNA ratio was significantly decreased approximately threefold in the spontaneously hypertensive rats compared with controls. This alteration in calcitonin gene related peptide mRNA levels is specific for dorsal root ganglia, because no strain differences in calcitonin gene-related peptide mRNA content were detected in heart or brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505085 TI - Insulin reduces reflex forearm sympathetic vasoconstriction in healthy humans. AB - Previous in vitro studies indicate that insulin modifies vascular reactivity to different agents. We have previously demonstrated that in normotensive humans physiological hyperinsulinemia is associated with an increase of forearm norepinephrine release but does not modify vascular resistance. To explore whether insulin modulates peripheral vasoconstriction induced by reflex sympathetic activation, we studied its effects on forearm hemodynamics (strain gauge plethysmography) during graded levels of lower body negative pressure (-5, 10, -15, and -20 mm Hg, each for 5 minutes) in normotensive subjects. For this purpose, eight subjects received an intrabrachial artery infusion of regular insulin at a systemically ineffective rate (0.05 milliunits/kg per minute) so that deep-venous insulin levels increased in the experimental forearm from 16.5 +/- 2.9 to 379.6 +/- 30 pmol/L (p < 0.01), whereas arterial insulin levels remained unchanged (from 40.9 +/- 8.6 to 43.1 +/- 7.9 pmol/L, NS). In the control arm, forearm vascular resistance (units) increased from 52.3 +/- 3 to a peak of 78.4 +/- 5 (p < 0.001) during lower body negative pressure. In the insulin exposed forearm, vascular resistance (46.4 +/- 2 at baseline) remained unchanged during insulin infusion (45.8 +/- 3, NS) and rose to a peak of 54.8 +/- 6 (p < 0.05) during lower body negative pressure. The response of forearm vascular resistance to lower body negative pressure was different in the two forearms (F = 4.506, p < 0.01, repeated-measures analysis of variance with grouping factor). Our results demonstrate that in normotensive subjects local physiological hyperinsulinemia reduces the forearm vasoconstrictive response to reflex sympathetic activation. PMID- 8505086 TI - Effects of ciglitazone on blood pressure and intracellular calcium metabolism. AB - Ciglitazone is the prototype of the thiazolidinedione class of compounds currently being developed for the treatment of insulin resistance and non-insulin dependent diabetes. The effects of thiazolidinediones on blood pressure and cell calcium metabolism are not well defined. In the obese Zucker rat, a widely studied model of insulin resistance associated with mild hypertension, we investigated the effects of ciglitazone on plasma insulin levels and mean arterial pressure. We also evaluated the effects of ciglitazone on the changes in cytosolic calcium induced by platelet-derived growth factor in A172 human glioblastoma cells and rat A10 vascular smooth muscle cells. Oral administration of ciglitazone, approximately 45 mg/kg per day for 4 weeks, induced significant reductions in plasma insulin levels (p < 0.001) and blood pressure (p < 0.05). Ciglitazone was also found to significantly attenuate the capacity of platelet derived growth factor BB homodimer to induce sustained increases in intracellular free calcium. These findings suggest that thiazolidinediones may offer a novel pharmacological approach to the treatment of hypertension, and raise the possibility that these compounds may affect blood pressure not only by affecting insulin metabolism but also by modifying the cell calcium response to pressor agents, growth factors, or both. PMID- 8505087 TI - Magnesium deficiency produces insulin resistance and increased thromboxane synthesis. AB - Evidence suggests that magnesium deficiency may play an important role in cardiovascular disease. In this study, we evaluated the effects of a magnesium infusion and dietary-induced isolated magnesium deficiency on the production of thromboxane and on angiotensin II-mediated aldosterone synthesis in normal human subjects. Because insulin resistance may be associated with altered blood pressure, we also measured insulin sensitivity using an intravenous glucose tolerance test with minimal model analysis in six subjects. The magnesium infusion reduced urinary thromboxane concentration and angiotensin II-induced plasma aldosterone levels. The low magnesium diet reduced both serum magnesium and intracellular free magnesium in red blood cells as determined by nuclear magnetic resonance (186 +/- 10 [SEM] to 127 +/- 9 mM, p < 0.01). Urinary thromboxane concentration measured by radioimmunoassay increased after magnesium deficiency. Similarly, angiotensin II-induced plasma aldosterone concentration increased after magnesium deficiency. Analysis showed that all subjects studied had a decrease in insulin sensitivity after magnesium deficiency (3.69 +/- 0.6 to 2.75 +/- 0.5 min-1 per microunit per milliliter x 10(-4), p < 0.03). We conclude that dietary-induced magnesium deficiency 1) increases thromboxane urinary concentration and 2) enhances angiotensin-induced aldosterone synthesis. These effects are associated with a decrease in insulin action, suggesting that magnesium deficiency may be a common factor associated with insulin resistance and vascular disease. PMID- 8505088 TI - Angiotensinogen is cleaved to angiotensin in isolated rat blood vessels. AB - The cleavage of synthetic tetradecapeptide renin substrate has been used to infer the presence of renin in the walls of isolated blood vessels; however, the conversion of natural angiotensinogen to angiotensin in isolated blood vessels has not been reported. We studied the release of angiotensinogen and the formation of angiotensins in a bloodless, perfused, isolated hind limb preparation of the rat. Perfusion with a modified Tyrode's solution resulted in spontaneous release of 4.7 +/- 1.5 pmol per 30 minutes of angiotensinogen as measured directly by radioimmunoassay. Western blot further identified the released material as angiotensinogen. Spontaneous release of angiotensins I and II was demonstrated by high performance liquid chromatography and radioimmunoassay. When highly purified rat angiotensinogen was added to the perfusate, release of angiotensin II was increased 14-fold compared with saline infusion. Captopril (10 mumol/L) inhibited angiotensinogen-induced angiotensin II release by 67% and led to an increase in angiotensin I release by 301%. Bilateral nephrectomy 24 hours before the experiments reduced basal angiotensin release below the detection limit and blunted angiotensinogen-induced angiotensin II formation by 95%. We conclude that active renin is present in the vessel wall and interacts with its natural substrate to form angiotensin peptides. Our data support the notion that the bulk of vascular renin is taken up from the circulation. PMID- 8505089 TI - Renal angiotensin receptor mapping in obese spontaneously hypertensive rats. AB - Obese spontaneously hypertensive rats (SHR) develop nephropathy with severe proteinuria, but lean littermates do not develop renal disease. Intrarenal angiotensin has been suggested to contribute to nephropathy in other experimental models. We examined the regulation of angiotensin receptors as a reflection of target tissue response to possible changes in the renin-angiotensin system. We visualized angiotensin receptors in kidneys of 6-8-month-old obese SHR and their lean littermates. Both obese and lean rats were hypertensive as determined by tail-cuff or by direct measurement. Histologic studies showed early glomerular sclerosis in obese but not lean rats. Autoradiographic visualization of angiotensin receptor binding sites in both obese and lean SHR showed glomeruli and medullary rays having the highest levels of binding with additional diffuse labeling in cortex and outer medulla. In obese rats, binding was reduced relative to lean littermates, particularly in the medulla, while intense binding in glomeruli was preserved. Loss of receptors did not reflect tissue damage, since the medulla showed no pathological changes. Biochemical assays of the binding of subtype-selective antagonists to 125I-angiotensin sites in intact sections showed that both losartan-sensitive and PD 123319-sensitive sites were decreased in nephrotic obese rats. We conclude that specific binding sites for angiotensin are decreased in obese SHR with early glomerular sclerosis, suggesting that angiotensin receptors may be regulated by pathogenic processes in this model of renal disease. PMID- 8505090 TI - Role of transforming growth factor-beta 1 in the cellular growth response to angiotensin II. AB - We have shown that angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle cells is dependent on the balance between proliferative and antiproliferative growth factors, specifically basic fibroblast growth factor and transforming growth factor-beta 1 (TGF-beta 1), respectively. We now present evidence, based on two phenotypically distinct cell cultures, that the ability to secrete the biologically active form of TGF-beta 1 is central to the growth response to Ang II. Two separate cultures were examined, one in which Ang II induces hypertrophy and the other in which Ang II induces hyperplasia. Ang II induces the expression of basic fibroblast growth factor twofold to fivefold in both cultures. Furthermore, both cultures express TGF-beta 1. In the culture that responds with hypertrophy, Ang II induces the expression of the active form of TGF-beta 1 twofold to threefold. However, in the culture that responds with hyperplasia, no active TGF-beta 1 was detected either at baseline or after Ang II exposure. Interestingly, all the TGF-beta 1 present was in the inactive, latent form. In the culture that responded with hyperplasia, Ang II induced a fourfold to fivefold increase in DNA synthesis. This increase could be abolished by the addition of active TGF-beta 1. Thus in these two cultures the ability to activate TGF-beta 1 dictates the cellular response to Ang II. These results support our hypothesis that a balance of proliferative and antiproliferative autocrine signals mediates the growth control of vascular smooth muscle cells. PMID- 8505091 TI - Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats. AB - Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role. PMID- 8505092 TI - Kidney is an important target for the antihypertensive action of an angiotensin II receptor antagonist in spontaneously hypertensive rats. AB - Inhibitors of the renin-angiotensin system lower blood pressure of spontaneously hypertensive rats, although plasma renin is not elevated. To test the hypothesis that the actions of angiotensin II within the kidney may contribute to the high blood pressure in spontaneously hypertensive rats, we infused valsartan, a subtype 1 angiotensin II receptor antagonist, via the suprarenal artery into the right kidney of conscious, freely moving, unilaterally nephrectomized (left) spontaneously hypertensive rats (12 to 14 weeks old). Valsartan (0.3 mg/kg per day for 48 hours) lowered blood pressure (change in blood pressure, -7 +/- 3, -19 +/- 4, and -26 +/- 4 mm Hg, n = 11, at 12, 24, and 48 hours) after intrarenal administration but had no significant effect on blood pressure after intravenous administration (change in blood pressure, 1 +/- 5, -3 +/- 4, and 10 +/- 5 mm Hg, n = 7, at 12, 24, and 48 hours). Infusion of vehicle (0.9% saline) intrarenally had no significant effect on blood pressure (change in blood pressure, 2 +/- 5, 1 +/- 6, and 0 +/- 7 mm Hg, n = 11, at 12, 24, and 48 hours). The maximum fall in blood pressure reached after intrarenal administration of this dose of valsartan was similar to the maximum fall induced after intravenous administration of higher doses (change in blood pressure, -14 +/- 5, -27 +/- 4, and -32 +/- 5 mm Hg, n = 7, at 12, 24, and 48 hours after 3 mg/kg per day i.v.). Thus, endogenous angiotensin II acting within the kidney appears to play an important role in the maintenance of high blood pressure in spontaneously hypertensive rats. PMID- 8505093 TI - Inhibition of central angiotensin responses by angiotensin type-1 receptor antibody. AB - Angiotensin type-1 receptor subtypes (AT1) are implicated in the physiological actions of angiotensin II in the brain. In the present study we used an AT1 receptor antibody and a polymerase chain reaction--synthesized AT1 receptor complementary DNA to show that the hypothalamus expresses significantly higher levels of AT1 receptor messenger RNA and protein compared with the brain stem. Intracerebroventricular injections of AT1-specific antibody blocks the dipsogenic and blood pressure responses induced by centrally injected angiotensin II. These results demonstrate the expression of AT1 receptor gene in the brain and that the AT1 receptor antibody is able to inhibit the physiological responses of angiotensin II mediated by the brain. PMID- 8505094 TI - The hypertensive Y chromosome elevates blood pressure in F11 normotensive rats. AB - Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the spontaneously hypertensive rat (SHR) model of hypertension and that the testes and androgen receptor contribute to the blood pressure rise. As an extension of our research, we have developed two new rat strains, SHR/a and SHR/y (F11) to study the Y chromosome. The objectives of the following research were 1) to study the blood pressure of rats with an SHR Y chromosome in a normotensive genetic background (SHR/y) or a normotensive Y chromosome in an SHR genetic background (SHR/a), 2) to determine the effect of male sex phenotype on the blood pressure of these rats, 3) to determine if testosterone replacement in castrated rats would restore blood pressure, and 4) to determine whether the Y chromosome from the SHR/y strain when crossed with a normotensive female can induce hypertension in androgen receptor-deficient male offspring. Blood pressure of male SHR/y rats was significantly higher than that of normotensive Wistar Kyoto males (p < 0.01), and SHR/a males had significantly lower blood pressure compared with that of the parent SHR strain (p = 0.05). Testosterone replacement in castrated rats of both strains (SHR/a and SHR/y) restored blood pressure to control levels. Normotensive female King-Holtzman rats heterozygous for the testicular feminization gene were crossed with F11 SHR/a and SHR/y males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505095 TI - Selective breeding to develop lines of baboons with high and low blood pressure. AB - Lines of baboons with high and low blood pressure were developed by selective breeding. Blood pressure was measured in 456 adult feral baboons under ketamine immobilization by direct arterial cannulation. Males with blood pressures two standard deviations and females with blood pressures one standard deviation above and below the cumulative mean were selected as progenitors. High males were mated with high females and low males were mated with low females. We measured blood pressure and plasma renin activity on 100 progeny, 54 males and 46 females, greater than 44 months of age with an abbreviated tether protocol and software program for data collection. Mean systolic and diastolic nighttime pressures for the high line were 126/72 and for the low line were 114/65 mm Hg. Line differences for systolic (12 mm Hg) and for diastolic (7 mm Hg) pressures were significant (p < 0.001). The line difference for plasma renin activity (1.1 [ng/mL]/hr) was not significant. Progeny pressures ranged from 84/49 to 191/126 mm Hg. There was no sex effect on blood pressure or plasma renin activity line differences. Heritability of systolic pressure was 0.46 +/- 0.19 and of diastolic pressure was 0.32 +/- 0.19. These results indicate that, by selective breeding and rigorous measurement of blood pressure, lines of baboons with significant difference in blood pressure can be developed. PMID- 8505096 TI - Proceedings of the Council for High Blood Pressure Research, 1992. Cleveland, Ohio, September 29-October 2, 1992. PMID- 8505097 TI - Corcoran Lecture. Sympathetic hyperactivity and coronary risk in hypertension. PMID- 8505099 TI - Immunogold localization of adenosine 5'-monophosphate-specific cytosolic 5' nucleotidase in dog heart. AB - Adenosine has a major regulatory function in the heart and many tissues. Our previous work showed that a cytosolic (not a membrane, as previously hypothesized) 5'-nucleotidase from dog heart has the kinetic properties consistent with it being the enzyme responsible for adenosine formation from adenosine 5'-monophosphate (AMP) in response to hypoxia or ischemia. In the present study, we evaluated the spatial distribution of AMP-specific cytosolic 5' nucleotidase in dog heart using electron microscopic immunogold localization. Polyclonal antibodies raised against purified cytosolic 5'-nucleotidase recognized the 43-kd subunit of the enzyme on Western blots of both purified enzyme and the soluble fraction of dog heart homogenates but did not react with proteins extracted from the membrane fraction. Purified cytosolic 5'-nucleotidase and 5'-nucleotidase activity present in the soluble fraction of heart homogenates were inhibited by anti-cytosolic 5'-nucleotidase, but the membrane fraction was not. The monospecific antibodies against the cytosolic 5'-nucleotidase were used for electron microscopic immunogold localization of cytosolic 5'-nucleotidase in dog heart tissue sections. Cytosolic 5'-nucleotidase was found in the cytoplasm of red blood cells, cardiac myocytes, and endothelium; the plasma membrane and interstitium were devoid of gold label. These results are the first to document the presence cytosolic 5'-nucleotidase in specific cell types in the heart and demonstrate the potential for these cell types to produce adenosine via cytosolic 5'-nucleotidase. PMID- 8505098 TI - Alterations in prostaglandin production in spontaneously hypertensive rat smooth muscle cells. AB - We have characterized angiotensin binding sites in cultured smooth muscle cells obtained from the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. In both strains of rats the binding of 125I-angiotensin II (125I-Ang II) in smooth muscle cells was time dependent and reached a maximum at 60 minutes. Scatchard analysis revealed a single binding site in both strains with equilibrium constants (KD) of 5.35 nmol/L in SHR and 3.47 nmol/L in WKY rats. Binding capacities (Bmax) in smooth muscle cells averaged 270 and 150 fmol/mg protein in SHR and WKY rats, respectively. Angiotensin peptides competed for 125I-Ang II binding with an order of potency of Ang II > angiotensin-(1-7) = angiotensin I. In smooth muscle cells of the SHR, basal prostaglandin E2 (PGE2) and prostacyclin (prostaglandin I2 [PGI2]) release were threefold and 15-fold lower than that found in WKY rat smooth muscle cells. Ang II as well as angiotensin-(1-7) stimulated PGE2 and PGI2 release in WKY rat smooth muscle cells. In smooth muscle cells from SHR, Ang II increased the production of both PGE2 and PGI2, whereas angiotensin-(1-7) enhanced only PGE2 but not PGI2 release. There was no significant difference between Ang II-stimulated PGE2 and PGI2 release or angiotensin-(1-7)-stimulated PGE2 production in SHR and WKY rat smooth muscle cells. However, angiotensin-(1-7)-stimulated PGI2 release was significantly lower (p < 0.0005) in SHR compared with WKY smooth muscle cells. Collectively, the data suggest that smooth muscle cells of SHR contain a higher number of angiotensin binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505100 TI - Adrenal kallikrein. AB - Kallikrein was identified in the adrenal glands of the rat. The enzyme was present in active and inactive forms (n = 9), since preincubation with trypsin increased kininogenase activity from 54.8 +/- 11.8 to 230 +/- 23 pg bradykinin per milligram protein per minute. Adrenal kininogenase activity was inhibited by 91% by phenylmethylsulfonyl fluoride (2 mM), 81% by D-Phe-Phe-Arg-chloromethyl ketone (1 microM), 88% by aprotinin (1,000 KIU), and only 16% by soybean trypsin inhibitor (50 microM). Preincubation with antibodies against rat urinary kallikrein resulted in over 90% inhibition of kininogenase activity. Immunoreactive glandular kallikrein was 30.7 +/- 4.8 ng/mg protein (n = 11). The apparent molecular weight of the adrenal kininogenase on gel filtration chromatography was 33,000 +/- 500 D. Both the adrenal enzyme and the purified submandibular gland kallikrein used as a control had the same mobility on alkaline polyacrylamide gel electrophoresis. To determine whether messenger RNA (mRNA) for glandular kallikrein is present in adrenal gland RNA, we used the polymerase chain reaction employing oligonucleotide primers and glandular kallikrein 32P complementary DNA (cDNA) as a probe, which should give a cDNA fragment of 370 bp. Southern blots of the amplified products revealed a fragment of the predicted size. In conclusion, glandular kallikrein has been identified in the adrenal glands. The presence of mRNA for glandular kallikrein suggests that kallikrein is synthesized locally in this tissue. This provides an anatomic basis for possible participation of a local kallikrein-kinin pathway in the regulation of adrenal function. PMID- 8505101 TI - Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats. AB - We have recently shown that the content of immunoreactive endothelin-1 is increased in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats compared with uninephrectomized control rats. We have also found by immunohistochemistry a significant increase in immunoreactive endothelin-1 in endothelial cells of aorta and mesenteric arteries of DOCA-salt hypertensive rats. In the present study, we investigated preproendothelin-1 gene expression in blood vessels of DOCA-salt hypertensive rats and uninephrectomized control rats. Northern blot analysis using a specific 32P-labeled complementary RNA probe for rat preproendothelin-1 of 319 base pairs revealed a fourfold to fivefold increase in abundance of preproendothelin-1 messenger RNA transcripts in both aorta and mesenteric arteries from DOCA-salt hypertensive rats. Thus, increased immunoreactive endothelin-1 content in blood vessels of DOCA-salt hypertensive rats is secondary to increased preproendothelin-1 gene expression. Exaggerated expression of the preproendothelin-1 gene in mineralocorticoid hypertension may contribute to the maintenance of elevated blood pressure. PMID- 8505102 TI - Inactivation of endothelin-1 by an enzyme of the vascular endothelial cells. AB - We previously investigated the inactivation of endothelin-1 by deamidase (lysosomal protective protein), present in many cells, including vascular smooth muscle cells. This enzyme, which we originally purified from human platelets, preferentially hydrolyzes peptides at the C-terminus with hydrophobic amino acids in the P1 or P1' position or both and thereby inactivates endothelin-1, which has a C-terminal sequence of Ile19-Ile20-Trp21-OH. We tested for the presence of deamidase in cultured bovine aortic endothelial cells. The final supernatant of the homogenized cells (S3) cleaved the deamidase substrate dansyl-Phe-Leu-Arg at a rate of 1.3 nmol/min per 10(6) cells at pH 5.5 at 37 degrees C. Endothelin-1 was completely inactivated by the S3 fraction as determined on rat thoracic aorta strips. The major site of inactivation was the Ile20-Trp21 bond, established by high performance liquid chromatography and by amino acid analysis where the main product was des-Trp21-endothelin-1. The hydrolysis of endothelin-1 (5.9 nmol/min per milligram of protein at pH 5.5 at 23 degrees C) by S3 was blocked mainly by inhibitors of deamidase, including diisopropyl fluorophosphate, but not by inhibitors of some other peptidases. This is the first report of a novel pathway of endothelin-1 metabolism in endothelial cells. Thus, endothelial cells, besides being the source of endothelin-1, contain an enzyme that inactivates it. PMID- 8505103 TI - Vasodilation to acetylcholine in primary and secondary forms of human hypertension. AB - Endothelium-dependent vasodilatation to acetylcholine is reduced in the forearm of essential hypertensive patients. To investigate whether endothelium-dependent vasodilatation is reduced also in secondary hypertension, we evaluated the effects of an intrabrachial infusion of acetylcholine on forearm blood flow (strain-gauge venous plethysmography) in essential hypertensive (n = 12), primary aldosteronism hypertensive (n = 8), and renovascular hypertensive (n = 8) patients and normotensive control subjects (n = 12). To further evaluate the role of a cyclooxygenase-dependent endothelium-derived vasoconstrictor substance, we repeated the infusion of acetylcholine in the presence of indomethacin. The effect of the direct vasodilator sodium nitroprusside was also examined. The vasodilatation to acetylcholine was reduced in essential, primary aldosteronism, and renovascular hypertensive patients compared with normotensive subjects. In contrast, the vasodilatation induced by sodium nitroprusside was similar in all groups of patients and control subjects. In the presence of indomethacin, the vasodilator effect of acetylcholine was increased in essential hypertensive patients but not in normotensive or in secondary hypertensive individuals. These data demonstrate an impairment of endothelium-dependent vasodilation in renovascular and primary aldosteronism hypertensive patients and indicate that a cyclooxygenase-dependent vasoconstrictor mechanism participates in the blunting of endothelium-dependent vasodilation in essential hypertensive patients. PMID- 8505104 TI - Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. AB - The influence of dietary sodium restriction and angiotensin II blockade on hypertension induced by a 25-day period of administration of the inhibitor of nitric oxide synthesis NG-nitro-L-arginine-methyl ester (10 mg/kg twice daily by gavage) was assessed in Wistar rats fed a normal or low sodium diet. In addition, the angiotensin II receptor blocker losartan (30 mg/kg once daily by gavage) was administered before and during NG-nitro-L-arginine-methyl ester in rats fed the normal sodium diet. At the end of the studies, conscious systolic arterial pressure increased similarly in NG-nitro-L-arginine-methyl ester-treated groups maintained on normal or low sodium intake. Moreover, a 25% reduction in cardiac output due to a decrease in stroke volume was observed in both groups. A slight but significant cardiac hypertrophic response was observed in hypertensive rats irrespective of sodium intake. At the completion of studies, plasma renin activity was similar to corresponding controls in the hypertensive groups on normal or low sodium intake. Losartan totally prevented the development of hypertension as well as the decrease in stroke volume and cardiac hypertrophy associated with NG-nitro-L-arginine-methyl ester treatment in rats on normal sodium intake. In conclusion, hypertension resulting from long-term blockade of nitric oxide synthesis was not affected by dietary sodium restriction. A crucial role for the renin-angiotensin system was demonstrated in this new model of hypertension. PMID- 8505105 TI - Role of nitric oxide in long-term angiotensin II-induced renal vasoconstriction. AB - In vitro studies have indicated that nitric oxide may play an important role in modulating the renal vascular actions of angiotensin II (Ang II). However, the physiological importance of this interaction in the long-term regulation of renal hemodynamics is unknown. Therefore, the goal of this study was to determine if long-term Ang II-induced renal vasoconstriction was potentiated by nitric oxide synthesis inhibition. The intrarenal effects of Ang II were examined in eight unilaterally nephrectomized, conscious dogs before and after systemic inhibition of nitric oxide synthesis. Ang II infusion into the renal artery at 0.5 ng/kg per minute resulted in decreases in renal plasma flow of 15% and 9% after 3 and 5 days, respectively. During this time, glomerular filtration rate decreased 12% after 3 days of angiotensin but was not significantly changed after 5 days. After 4 days of recovery from Ang II, nitric oxide synthesis was inhibited with intravenous NG-nitro-L-arginine-methyl ester (L-NAME) at 10 micrograms/kg per minute for 5 days, and this caused a significant decrease in renal plasma flow but no change in glomerular filtration rate. Infusion of Ang II into L-NAME pretreated dogs for an additional 5 days further decreased renal plasma flow and glomerular filtration 14% and 11%, respectively. However, the effects of Ang II and L-NAME on renal plasma flow were only additive on days 3 and 5 of this period, and the effects on glomerular filtration were additive on day 3 but were potentiated on day 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505106 TI - Role of renal interstitial pressure as a mediator of sodium retention during systemic blockade of nitric oxide. AB - The role of renal interstitial pressure was examined in mediating the sodium retention induced by blockade of nitric oxide synthesis. The effects of intravenous NG-nitro-L-arginine-methyl ester (L-NAME), a synthesis inhibitor, on renal hemodynamics, renal interstitial hydrostatic pressure, and sodium and lithium excretion were determined. L-NAME (50 micrograms/kg per minute) was infused for 75 minutes in Sprague-Dawley rats (n = 7) in which renal perfusion pressure was permitted to rise in parallel with systemic arterial pressure and in rats (n = 8) in which renal perfusion pressure was serocontrolled constant at basal levels. Infusion of L-NAME raised renal perfusion pressure from 122 +/- 6 to 157 +/- 4 mm Hg in the nonservocontrolled group but not in the servocontrolled group (118 +/- 3 mm Hg). L-NAME decreased renal plasma flow and glomerular filtration rate to the same level in both rat groups. L-NAME significantly decreased sodium excretion (1.38 +/- 0.41 to 0.36 +/- 0.14 microEq/min and 1.19 +/- 0.46 to 0.30 +/- 0.05 microEq/min, respectively), fractional excretion of lithium (25.7 +/- 1.7% to 16.7 +/- 2.3% and 25.6 +/- 4.0% to 18.2 +/- 1.7%), and renal interstitial hydrostatic pressure (6.4 +/- 1.4 to 3.2 +/- 0.9 mm Hg and 6.3 +/- 1.8 to 2.7 +/- 0.9 mm Hg) in servocontrolled and nonservocontrolled groups. However, there was no significant difference in the renal hemodynamic and excretory responses to L-NAME between the servocontrolled and nonservocontrolled groups. In summary, reductions in sodium excretion during inhibition of nitric oxide synthesis are associated with significant reductions in renal interstitial hydrostatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505107 TI - Kinin actions on renal papillary blood flow and sodium excretion. AB - Infusion of bradykinin into the renal medullary interstitium (0.1 micrograms/min, n = 6) significantly increased renal papillary blood flow as measured by laser Doppler flowmetry to 117 +/- 3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 +/- 5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor NG-nitro-L-arginine-methyl ester (2 micrograms/min, n = 7) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism. PMID- 8505108 TI - Bradykinin does not modulate the natriuretic response to atrial natriuretic factor in rats with aortocaval fistula. AB - Rats with aortocaval fistula, an experimental model of congestive heart failure (CHF), display two distinct patterns of sodium excretion: some rats develop marked sodium retention and worsening edema with urinary excretion of sodium (UNaV) < 200 microEq per 24 hours, i.e., uncompensated CHF, whereas in others sodium balance rapidly returns to normal (UNaV > 1,400 microEq per 24 hours), i.e., compensated CHF. Similar patterns of sodium excretion are found in patients with CHF. The mechanisms underlying these responses are not fully understood. The present study was designed to assess whether bradykinin plays a role in the compensatory response to CHF. Infusions of either 10 or 50 micrograms/kg per minute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operated control animals produced significant increases in urine flow and fractional excretion of sodium (FENa). Infusions of ANF at the same doses into rats with compensated CHF increased FENa from 0.11 +/- 0.03% to a maximum of 6.10 +/- 1.30%, whereas the rise in FENa in animals with uncompensated CHF was significantly reduced (0.05 +/- 0.01% to 0.59 +/- 0.18%) compared with sham operated controls (0.23 +/- 0.05% to 8.32 +/- 1.0%) or the group with compensated CHF. Treatment of the compensated rats with the bradykinin antagonist HOE-140 (D Arg,[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) given at a rate of 100 nmol/kg per hour did not affect their renal response to the ANF. In addition, infusion of the bradykinin antagonist alone into compensated rats with aortocaval fistula had no significant effect on their basal urinary flow rate or sodium excretion during the infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505109 TI - Low calorie unrestricted protein diet attenuates renal injury in hypertensive rats. AB - In the present investigation we researched the effects of low calorie diet without protein restriction on the renal function and glomerular injury of uninephrectomized spontaneously hypertensive rats. We compared the findings with those that occurred in two different groups of uninephrectomized spontaneously hypertensive rats: one treated with oral hydralazine (10 mg/kg per day) and a second fed regular food. The low calorie diet and hydralazine treatment significantly reduced intra-arterial blood pressure in each group (p < 0.05 and p < 0.001, respectively). The control group showed at the end of the experiment a slight but not significantly different increase in the intra-arterial blood pressure. Low calorie diet was more effective in protecting the kidney function. Creatinine clearance after treatment was significantly higher in uninephrectomized spontaneously hypertensive rats on a low calorie diet than in either the hydralazine-treated or control groups (p < 0.01). The 24-hour urinary protein excretion in the low calorie diet group was significantly lower than in the control group (p < 0.05) and lower but not statistically different from the hydralazine-treated group. The mean glomerular injury index of the remaining kidney in the low calorie diet group was lower than in either the hydralazine treated or control groups (p < 0.05), and the mean mesangial expansion index in the low calorie diet group was significantly lower than in the control group (p < 0.05). The favorable effect of low calorie diet on renal function was independent of protein restriction or sodium and potassium content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505110 TI - Angiotensin blockade and the progression of renal damage in the spontaneously hypertensive rat. AB - The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension. PMID- 8505111 TI - Clofibrate prevents the development of hypertension in Dahl salt-sensitive rats. AB - We have reported that cytochrome P-450-dependent omega-hydroxylation of arachidonic acid is reduced in microsomes prepared from the renal outer medulla of Dahl salt-sensitive (SS/Jr) rats, but the functional significance of this observation is unknown. The present study examined whether long-term induction of renal fatty acid omega-hydroxylase with clofibrate would alter the development of hypertension in Dahl SS/Jr rats. Dahl SS/Jr rats were placed on a high salt diet (8.0% NaCl) and given either vehicle or clofibrate (80 mg/day) in their drinking water. After 4 weeks of a high salt diet, mean arterial pressure averaged 170 +/- 3 mm Hg in vehicle-treated (n = 17) and 127 +/- 2 mm Hg in clofibrate-treated (n = 19) SS/Jr rats. Clofibrate had no effect on arterial pressure in Dahl salt resistant rats. The antihypertensive effect of clofibrate was reversible. Mean arterial pressure rose from 131 +/- 4 to 182 +/- 8 mm Hg in the first week after clofibrate treatment (n = 6) was discontinued. Clofibrate had no effect on arterial pressure in SS/Jr rats (n = 9) in which hypertension was already established by feeding the rats a high salt diet for 4 weeks before the study. In clofibrate-treated SS/Jr rats (n = 12), the omega-hydroxylation of arachidonic and lauric acids by renal cortical and outer medullary microsomes was greater than that seen in vehicle-treated rats (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505112 TI - Effect of low sodium diet or potassium supplementation on adolescent blood pressure. AB - The roots of essential hypertension extend back into the first two decades of life, suggesting that effective intervention during those years may lead to a reduction in the incidence of adult hypertension. Decreasing the dietary sodium/potassium ratio offers a potentially effective approach to blood pressure reduction. This study tested the feasibility of 3-year sodium reduction or potassium supplementation in adolescents and the effect of these interventions on the rate of rise of blood pressure during adolescence. After 19,452 5th to 8th grade students were screened, 210 from the upper 15 percentiles of blood pressure distribution (105 boys, 105 girls) were randomly assigned to one of three groups: low sodium diet (70 mmol sodium intake per day), potassium chloride supplementation (normal diet plus 1 mmol/kg potassium chloride per day), or placebo (normal diet plus placebo capsule). Capsules for the potassium chloride and placebo groups were administered in a double blind protocol. Blood pressure was measured every 3 months for 3 years. The effect of the intervention was determined by comparing the rate of rise (slope) of blood pressure among the groups using a random-coefficient growth curve model. The boys groups and the girls placebo group had similar positive blood pressure slopes that were significantly different from zero. The girls low sodium group had a slightly negative slope (significantly lower than the slope of the girls placebo group), and the girls potassium group had a slightly positive slope. Both of these slopes were not significantly different from zero and were significantly lower than the slopes of the respective boys groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505113 TI - Insertion of the distal locking screws in femoral nailing: a simplified technique. AB - The use of a cannulated drill bit for the insertion of the distal locking screws is described. It is shown to reduce operating time and radiation exposure compared with the free-hand technique. PMID- 8505114 TI - Quadricepsplasty following femoral shaft fractures. AB - The results of 12 quadricepsplasties performed on 10 patients with stiff knees following united femoral shaft fractures are reviewed. All fractures were caused by high-velocity road traffic accidents and were associated with a variety of features which led to multiple operations and delayed union. The increased range of flexion achieved in this series is higher than in those reported previously. PMID- 8505115 TI - Fracture of the lateral malleolus with talar tilt: primarily a calcaneal fracture not an ankle injury. AB - We report four cases in which radiographic features of a fracture of the lateral malleolus and talar tilt of varying severity were associated with a displaced fracture of the calcaneum. In two cases, the initial diagnosis was of a primary ankle injury which led to inappropriate initial management. Gross fracture subluxation of the posterior subtalar joint had occurred in all four cases but could only be fully appreciated after CT examination of the hindfoot. Operative reduction and internal fixation of the calcaneal fracture led to spontaneous reduction of the talar displacement. The association of a swollen hindfoot, talar tilt and a flake fracture of the lateral malleolus must alert clinicians to this injury. PMID- 8505116 TI - Sternal fracture: what investigations are indicated? AB - A retrospective study of 55 patients with sternal fractures is presented in an attempt to determine which investigations are predictive of complications. We conclude that isolated sternal fractures, in the absence of clinical evidence of cardiac or respiratory complications, and with a normal electrocardiogram and postero-anterior chest radiograph, require no further investigation. PMID- 8505117 TI - Ankle fractures in the elderly: MUA versus ORIF. AB - A series of 80 patients over the age of 60 years with ankle fractures were reviewed retrospectively. 'Pilon' and talar fractures were excluded; 41 were treated conservatively (MUA) and 39 by operation (ORIF). The mean follow-up was 28 months (range 18-38 months) in the ORIF group and 25.5 months (range 12-40 months) in the MUA group. A statistically significant proportion of patients were satisfied with regard to pain, swelling, stiffness, instability and ranges of movement after ORIF. Anatomical congruity of the ankle mortice was better maintained following ORIF. Poor subjective and objective end results correlated with malalignment of the ankle mortice on the final radiograph at follow-up. PMID- 8505118 TI - Pressure in plaster backslabs after surgery for ankle fractures. AB - Concern over the safety of applying a cast when postoperative swelling might be expected, prompted a study of the pressure inside backslabs. Using a modified Sengstaken tube, pressure measurements were taken from blackslabs applied for temporary support after open reduction and internal fixation of 15 ankle fractures. The mean pressure rise was 4.6 cmH2O (3.4 mmHg), the maximum increase in any cast was 18 cmH2O (13.2 mmHg), and the maximum pressure reached was 27.5 cmH2O (20.2 mmHg). There were no clinical signs or symptoms of excessive compression by the cast and in all cases the pressure had reached its maximum and begun to fall within 3 h of the operation. The ankle swelling associated with injury and surgery seems not to produce an unacceptable pressure rise within backslabs applied postoperatively. PMID- 8505119 TI - The two-part proximal humeral fracture: a review of operative treatment using two techniques. AB - A review of 45 patients who have undergone surgery for two-part fractures of the proximal humerus (Neer Group III) is reported using two operative techniques, AO plating and intramedullary Rush pins. Good functional results were obtained using the former technique in seven out of eight of the patients under the age of 50 years who mainly sustained their original injury as a result of high-energy motor vehicle accidents. However, in the more common low-energy, osteoporotic fracture in the elderly population, results were unsatisfactory in 12 out of 14 cases where AO plating was used, usually as a result of fixation failure. The Rush pin technique produced more reliable results in this age group, with satisfactory functional scores being obtained in 16 out of 23 patients. It is suggested that the Rush pin technique is preferable to plate fixation in the more common osteoporotic insufficiency fracture in the elderly. PMID- 8505120 TI - Post-traumatic ligamentous instability of the atlantoaxial joint: a comparison between the Gallie and Brooks fusions. AB - We reviewed 37 patients following a posterior spinal fusion for traumatic ligamentous instability of the atlanto-axial joint. All patients were neurologically intact and the atlanto-dental interval ranged from 5 to 9 mm. A Gallie fusion was performed in 19 patients, a Brooks fusion in 16 patients and an occipitocervical fusion in two patients. A SOMI brace was used postoperatively for 12 weeks. Bony fusion was obtained in 32 patients. Displacement occurred in 11 patients, five of whom developed non-union. PMID- 8505121 TI - Traumatic dislocation of the testicle. PMID- 8505122 TI - Dislocated intra-articular fracture of anterior rim of glenoid treated by open reduction and internal fixation. PMID- 8505123 TI - Cardiac injury: tuberculous pericardial disease as a mimic in penetrating chest injury. PMID- 8505124 TI - Hypoglossal nerve palsy following hyperextension neck injury. PMID- 8505125 TI - Delayed presentation of a vascular injury by an ilizarov external fixator. PMID- 8505126 TI - Closed intramedullary nailing complicated by breakage of plastic medullary tube. PMID- 8505127 TI - Interlocking screw length in intramedullary nailing. PMID- 8505128 TI - Double interphalangeal joint dislocation in a little finger. PMID- 8505129 TI - Diagnostic peritoneal lavage using a trocar-mounted chest tube. PMID- 8505130 TI - Neck injuries from rear impact road traffic accidents: prognosis in persons seeking compensation. AB - We studied the natural history and prognostic factors in 100 patients who had sustained neck sprains in rear impact road traffic accidents, and who had all originally been seen for medicolegal reports. They were seen for clinical and radiological review at a mean of 8 years after injury. The detailed medicolegal reports from the early years were available on all patients, and were used to supplement the information obtained at review. Of the patients, 50 per cent had significant pain at 8 months, decreasing to 22 per cent at 2 years and 18 per cent at 3 years. At review, 45 per cent were free of pain, and 14 per cent had significant pain. Front seat position, pain within 12 h of injury, past history of neck pain and degenerative changes on radiographs were associated with a longer duration of significant pain (P < 0.05). Early onset of pain was also associated with a worse level of pain at review. The timing of compensation was not associated with improvement in symptoms. The injury had not accelerated the development of degenerative changes. PMID- 8505131 TI - Acute neck sprain after road traffic accident: a long-term clinical and radiological review. AB - A retrospective review of 21 patients between 10 and 19 years after a soft tissue injury to the cervical spine was undertaken. The clinical data showed a persistence of symptoms in 18 (86 per cent) of patients without any deterioration in the clinical signs. The radiological assessment did not show any evidence of injury leading to, or correlating with, the development or progression of degenerative changes in the cervical spine. PMID- 8505132 TI - Occult spinal cord injury in traumatized children. AB - The existence of spinal cord injury without radiological abnormality (SCIWORA) has been recognized for some years. Two cases of SCIWORA in children are presented which highlight the possibility of severe spinal cord injury without any physical or radiological signs. The injury may occur at any level. It is recommended that normal procedures used for spinal immobilization in adults are inappropriate in the case of children and all unconscious children should be treated with full spinal immobilization until clinical assessment of neurological function is possible. PMID- 8505133 TI - Audit of closed tibial fractures: what is a satisfactory outcome? AB - We performed an audit of closed non-articular tibial fractures that presented to a teaching hospital during 1 year. A total of 52 fractures in 51 patients was seen. We found that the great majority of fractures occurred in the third quarter of the tibia. Standards are essential for audit, but on review of the literature we found wide discrepancy between the standards set to judge the outcome of tibial fractures. Depending on the standards selected, we can show that 4 per cent or 42 per cent of our patients can be said to have a suboptimal outcome. We found that there is little hard evidence to support the published standards. Long term studies of tibial fractures are required to derive rational standards to allow the most effective and efficient treatment of each case and to enable surgeons to make a meaningful audit of their results. PMID- 8505134 TI - Treatment of subtrochanteric fractures with the AO dynamic condylar screw. AB - The AO/ASIF dynamic condylar screw (DCS) was used for the operative treatment of 15 patients, nine women and six men, with subtrochanteric fractures of the femur. The mean age was 70 years (range 20-95 years). The patients were followed for 18 to 30 months. Three patients developed healing disturbances, two of whom had an insufficient medial cortical bone support. The fixation device failed in two hips and it loosened in one. We conclude that the DCS is an alternative to the 95 degrees angled blade-plate in the operative treatment of subtrochanteric fractures of the femur. We also stress the importance of an adequate medial bone support. PMID- 8505135 TI - Subtrochanteric fractures of the femur treated with the Zickel nail. AB - In a retrospective study of 41 subtrochanteric fractures treated with Zickel intramedullary nails (with a follow-up period of at least 1 year) there was a union rate of 100 per cent (39/39). Union occurred between 4 and 7 months (average healing time 5.2 months). There were no implant failures. Four patients have had their Zickel nails successfully removed. In 48 per cent of the cases we had some difficulties with the stability of the fracture, and in 14 per cent, all of them long oblique comminuted fractures, skeletal traction was needed for 6 weeks. In nine cases there was a shortening of 1.5-4 cm (average 2 cm). Although our overall experience with the Zickel nail has been favourable in the treatment of non-union of subtrochanteric fractures, and with the elderly patients who had a simple subtrochanteric fracture secondary to minor trauma, we no longer recommend its use in the treatment of subtrochanteric fractures with marked comminution, because it does not give sufficient rotational and axial stability. PMID- 8505136 TI - Assessment of hip abductor function in relation to peritrochanteric heterotopic ossification after closed femoral nailing. AB - The relationship between peritrochanteric heterotopic ossification and the strength of hip abduction after closed intramedullary nailing for femoral shaft fractures was investigated in 25 patients after a mean follow-up of 2 years (range 9 months to 4 years). The power of hip abduction was assessed and compared with the normal hip. Of the 21 patients with heterotopic ossification, 16 had measurable weakness of hip abduction. Grade III heterotopic ossification resulted in 8-20 per cent weakness of hip abduction, but this was not associated with any disability or symptoms. Clinically important abductor weakness is more likely to be due to ipsilateral fractures or a long nail rather than heterotopic ossification. PMID- 8505137 TI - The effect of splenopentin (DA SP-5) on in vitro myelopoiesis and on AZT-induced bone marrow toxicity. AB - Splenopentin (DA SP-5) is a pentapeptide corresponding to the amino acid sequence 32-36 (Arg-Lys-Glu-Val-Tyr) of the splenic hormone splenin. We examined the influence of DA SP-5 on bone marrow progenitor cell (BMC) proliferation. DA SP-5 acts as a co-stimulant for recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF) in the induction of human BMC derived colony formation in vitro (colony-forming units). When exposed to DA SP-5 and thereafter to AZT and rHuGM-CSF, BMCs show a colony-forming response similar to that after cultivation with the rHuGM-CSF alone. In contrast, when exposed to AZT and rHuGM CSF (and not preincubated with DA SP-5) the colony formation was reduced. A similar pentapeptide thymopentin (Arg-Lys-Asp-Val-Tyr) did not influence colony formation by human BMCs. We assume that DA SP-5 could support therapeutic effects of rHuGM-CSF. PMID- 8505138 TI - Foreign body granulomatous inflammation increases the sensitivity of splenocytes to immunomodulation by 1,25-dihydroxyvitamin D3. AB - 1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, partially inhibits antigen and mitogen-driven lymphocyte stimulation. We studied the effect of granulomatous inflammation on the sensitivity of lymphocytes to 1,25 dihydroxyvitamin D3 in vitro, measuring the inhibitory effect of 1,25 dihydroxyvitamin D3 on mitogenesis of splenocytes of mice with chronic inflammation induced by subcutaneous injection of talc. Systemic manifestations of the local inflammation included loss in body weight, splenomegaly, enhanced DNA synthesis by freshly isolated splenocytes and enhanced prostaglandin secretion by activated splenocytes. Splenocytes from animals with local inflammation were more susceptible to inhibition by 1,25-dihydroxyvitamin D3, but not by prostaglandin E2. This increased sensitivity to 1,25-dihydroxyvitamin D3 was abolished by blocking prostaglandin synthesis in splenocyte cultures with indomethacin and was restored by adding prostaglandin E2. This effect cannot be attributed to enhanced prostaglandin synthesis in the presence of 1,25 dihydroxyvitamin D3, but is probably due to a qualitative change in the response of splenocytes from inflamed animals to the combined action of 1,25 dihydroxyvitamin D3 and prostaglandin E2. PMID- 8505139 TI - Effect of in vivo administration of cisplatin on the colony forming ability of murine bone marrow cells. AB - In vitro colony forming ability of bone marrow cells obtained from cisplatin treated C3H/He mice was studied. Mice were administered cisplatin in a single intraperitoneal dose of 10 mg/kg body wt, 24 h prior to the harvest of femoral bone marrow cells. Incubation of untreated bone marrow cells without any CSF in vitro showed little colony forming ability which was marginally enhanced in cisplatin-treated bone marrow cells. Presence of M-CSF (250 U/ml) or GM-CSF (250 U/ml) in the culture medium significantly augmented the colony forming ability of both untreated and cisplatin-treated bone marrow cells. In the presence of M-CSF, colony forming units-macrophage (CFU-M) were predominantly high in untreated bone marrow cells, followed with CFU-granulocyte-macrophage (CFU-GM). The number of CFU-M was significantly up-regulated in response to M-CSF in bone marrow cells obtained from cisplatin administered mice, whereas the number of CFU-GM remained unchanged, as compared to untreated mice. Both CFU-M and CFU-GM were enhanced in the presence of GM-CSF in untreated bone marrow cells. Cisplatin-treated bone marrow cells on incubation in the presence of GM-CSF showed a significant enhancement of CFU-M and GM as compared to untreated samples. IL-1 (100 U/ml) in the presence of M-CSF significantly up-regulated colony forming ability of cisplatin-treated bone marrow cells, whereas TNF (100 U/ml) inhibited the colony forming ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505140 TI - Inhibition of mouse spleen cell activity by organotin compounds: effect of attachment of a maltose residue to the organotin group. AB - Studies are reported on the inhibition of DNA synthesis and the lowering of cell viability caused by bis(tributyltin) oxide in mouse spleen cells cultured in the presence and absence of the B-lymphocyte mitogen, bacterial lipopolysaccharide. When a maltose residue is introduced into the organotin compound these toxic effects are increased. It is suggested that the maltose residue facilitates entry of the organotin compound into the cells. PMID- 8505141 TI - IFN-gamma treatment of rodents infected with erythrocytic stages of Plasmodium chabaudi: differential effects according to the immunological status. AB - Recombinant rat interferon-gamma (rrIFN-gamma) was tested for its antimalarial activity in three different models of Plasmodium chabaudi-blood stage malaria. Doses ranging from 1 x 10(4) to 1 x 10(5) U of rrIFN-gamma were used in each model. In BALB/c mice (lethal infection), prophylactic treatment with daily intraperitoneal (i.p.) injections reduced parasitemia and delayed mortality. In contrast, subcutaneous administration of rrIFN-gamma was inefficient, as was curative schedule of i.p. administration. Euthymic Fischer rats, which develop an acute and resolutive infection, were partly protected by i.p. prophylactic administration of rrIFN-gamma. Parasitemia was reduced without being lengthened, resulting in a marked decrease in parasite burden. Subcutaneous administration was less efficient whereas curative schedule was not. Athymic (nude) Fischer rats which present a longlasting and stable infection were treated with prophylactic and curative schedules of i.p. administration of rrIFN-gamma. In each case, rrIFN gamma-treated nude rats, as control nude rats, were unable to resolve their chronic infection. The conditions required to obtain a beneficial effect are thus restrictive for a therapeutic use in humans. Moreover, these results show that, despite the fact that IFN-gamma is considered as a major component of the immune response, this cytokine alone is not sufficient to induce the totality of the effector mechanisms necessary to cure malarial infections. PMID- 8505142 TI - Hematopoietic effects in mice exposed to deltamethrin and hydrocortisone. AB - The effects of deltamethrin on bone marrow and spleen progenitor cell responsiveness to granulocyte and macrophage colony-stimulating factors were evaluated. Deltamethrin was tested in parallel with hydrocortisone to further investigate some similarity in the in vivo effects of both compounds observed in previous studies in our laboratory. In vivo effects were studied after the subcutaneous administration in mice of three 5 mg/kg injections of deltamethrin and a single 30 mg/kg injection of hydrocortisone to Balb/c mice. Soft agar colony formation, marrow and spleen cell counts, body, spleen and thymus weights were determined. Data obtained in vivo indicate that deltamethrin and hydrocortisone reversibly increase the formation of granulocyte and macrophage colonies in the marrow, but not in the spleen. No changes were observed in total and differential cell counts in the marrow and spleen and spleen weights. Treatment with both compounds, however, resulted in a dramatic reduction in thymus weights. Assays for endotoxin demonstrate that these effects were not due to the liberation of endotoxin. In vitro addition of 10(-5), 10(-6) and 10(-7) M deltamethrin and hydrocortisone to marrow cultures from untreated mice resulted in different effects from those observed in vivo. Hydrocortisone increased granulocyte and reduced macrophage colonies, whereas deltamethrin was without in vitro effects. It is suggested that deltamethrin effects are due to an indirect action on the hypothalamic-pituitary axis leading to increased corticosteroid levels. The importance of biotransformation mechanisms is also emphasized. PMID- 8505143 TI - A mechanism of retinoid potentiation of murine T-cell responses: early upregulation of interleukin-2 receptors. AB - The capacity of retinoids to amplify the proliferative response of BALB/c lymphocytes to concanavalin A (Con A)2 in the presence of exogenous interleukin-2 (IL-2) and the induction of IL-2 receptors (IL-2R) on L3T4+ and Lyt-2+ T-cells was evaluated. Preincubation with Con A for 8 h in the presence of retinoids resulted in a greater than two-fold increase in spleen cell proliferative response to Con A plus rIL-2 over the following 72 h relative to the response of cells preincubated with Con A alone. Peak potentiation of IL-2 responses occurred over a pharmacologic range of retinoic acid (RA) concentration (10(-10)-10(-8) M) in the presence of 20 U/ml rIL-2. This potentiation of the response to IL-2 was likewise observed after 8 h prestimulation with Con A with splenic T-cells enriched by passage over nylon wool. Preincubation of the spleen cells with Con A plus RA without the subsequent addition of IL-2 resulted in a proliferative response that was potentiated nearly to the level of the response produced by subsequent addition of IL-2 to Con A-activated cells. Preincubation of the cells with Con A in the presence of RA produced a true synergy with IL-2; the resulting increase in response was greater than the sum of the increases produced by RA or IL-2 alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505144 TI - Enhancement of in vitro antibody production of murine splenocytes by ascorbic acid 2-O-alpha-glucoside. AB - Using an antigen-specific plaque forming cell (PFC) assay, we have studied the effect of ascorbic acid 2-O-alpha-glucoside (AA-2G), a new stable derivative of ascorbic acid (AsA), on antibody production in cultured murine splenocytes in comparison with that of AsA. A single addition of AA-2G (0.0625-1.0 mM) remarkably stimulated both anti-SRBC (sheep red blood cell, TD antigen) and anti TNP (trinitrophenyl, TI antigen) PFC responses in a dose-dependent manner, although AsA failed to stimulate their responses. However, repeated additions of AsA at 12-h intervals during the cultivation resulted in enhancement of the anti SRBC PFC response, and the magnitude of stimulation was comparable to that obtained by a single addition of AA-2G. AA-2G's effect was abrogated in the presence of castanospermine (alpha-glucosidase inhibitor) in the medium, indicating that the immunostimulation brought about by AA-2G is attributed to AsA released from the glucoside by alpha-glucosidase of cultured cells. In fact, the cells maintained a certain amount of AsA for a relatively long time after exposure to AA-2G. In contrast, AsA levels in the cells treated with AsA quickly decreased. AA-2G markedly enhanced lipopolysaccharide(LPS)-induced proliferative response, and could affect the concanavalin A (Con A) response weakly. These results suggest that AsA effectively potentiates B-cell functions in the humoral immune system. Thus, we conclude that AA-2G is capable of enhancing antibody production in the cultured splenocytes via a continuous supplementation of AsA and that AA-2G is available for long-term cell cultures as a useful tool for analyzing biological function of AsA. PMID- 8505145 TI - Effect of interferon-gamma, tumor necrosis factor, interleukin-1 and interleukin 6 on the modulation of anti-tumor responses of bone marrow derived macrophages. AB - Non-adherent bone marrow cells (NABMC) obtained from BALB/c mice were incubated in medium alone or containing granulocyte--macrophage-colony stimulating factor(GM-CSF) or macrophage-colony stimulating factor (M-CSF) for 4 days to obtain bone marrow derived macrophages. Treatment of GM-CSF or M-CSF derived macrophages with interferon-gamma (IFN-gamma) (50 U/ml), tumor necrosis factor (TNF) (500 U/ml), interleukin-1 (IL-1) (200 U/ml) or interleukin-6 (IL-6) (100 U/ml) for 24 h rendered them significantly cytotoxic to different tumor cells. These macrophages also produced enhanced amounts of soluble or membrane associated TNF. Medium derived macrophages showed little cytotoxicity against tumor cells and production of TNF on treatment with TNF, IFN-gamma, IL-1 or IL-6. M-CSF or GM-CSF derived macrophages on treatment with IFN-gamma showed enhanced release of nitrite as compared to medium derived macrophages. TNF, IL-1 or IL-6 did not induce nitrite production in bone marrow derived macrophages. Out of the different combinations tested, only IFN-gamma plus TNF-treated macrophages showed enhancement in nitrite production as compared to that of IFN-gamma alone. PMID- 8505146 TI - Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder. AB - We have investigated the effect of thymostimulin on the major histocompatibility (MHC) unrestricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) from patients with superficial transitional cell carcinoma (TCC) of the bladder. PBMNC from patients and healthy controls were incubated in the presence of thymostimulin for varying periods of time (2 or 18 h or 5 days), and were used as effectors against 51Cr-radiolabeled natural killer (NK)-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxic assays. In 6 out of 14 patients analyzed, thymostimulin enhanced the cytotoxic activity of PBMNC against NK sensitive target cells in a dose-dependent manner. This cytotoxic inducer effect of thymostimulin was maximal after 18 h of culture. Thymostimulin failed to induce lytic activity in PBMNC from TCC patients against NK-resistant target cells. We also found that thymostimulin could synergize with interleukin-2 in inducing non-MHC restricted cytotoxic activity in PBMNC from TCC patients. In conclusion, we have demonstrated that thymostimulin can enhance the natural killer cytotoxic activity of PBMNC from patients with TCC of the bladder. PMID- 8505147 TI - Beneficial effects of SK&F 105685 in rat adjuvant arthritis: prophylactic and therapeutic effects on disease parameter progression. AB - Prophylactic administration of SK&F 105685 (N, N-dimethyl-8,8,-dipropyl-2 azaspiro[4.5]decane-2-propanamine dihydrochloride) at 30 mg/kg/day inhibited hindpaw lesions in adjuvant arthritic (AA) rats following 16 (84% inhibition) and 24 (70% inhibition) days of treatment. In a therapeutic protocol, where dosing was initiated on day 10 after disease induction, SK&F 105685 (20 mg/kg/day) effectively halted disease progression, and the inflammatory lesion was suppressed by 70% following treatment for 20 days. Histological evaluation of the joint periarticular soft tissue, bone and articulation (joint space and joint surface) from therapeutically treated rats showed a clear beneficial effect. Most rats presented moderate lesions rather than the severe lesions seen in the AA animals. AA control rats and AA rats treated prophylactically or therapeutically with SK&F 105685 had significant and similar increases in their total white blood cell (WBC), neutrophil, monocyte and platelet counts. Although increases were seen in the absolute number of neutrophils and platelets, there were no differences in the levels of leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid (HHT), per cell when these cells were stimulated with the calcium ionophore A23187. These results, describing the beneficial effects of SK&F 105685 administered therapeutically to the AA rat, indicate that this compound possesses properties desirable of an anti-arthritic agent and may potentially modify the disease outcome. PMID- 8505148 TI - Route of administration may determine the biological effects of RU 41,740 (Biostim). Trapping of 99mTc-labelled human albumin colloids in mice. AB - Experiments have been conducted in mice to examine whether treatment with the immunostimulating drug RU 41,740 (Biostim) may change the distribution of i.v. injected radiolabelled human albumin colloids. It was observed that a single i.p. injection of Biostim (1 ng-1000 micrograms) significantly enhanced trapping of the particles in spleen and lungs. The effect, which was dose-dependent, was most pronounced in the lungs where more than a 10-fold increase could take place. On the contrary, oral administration of Biostim caused a dose-dependent decrease of colloid trapping in the lungs. Further experiments showed that oral administration of Biostim resulted in the appearance of soluble factors in the blood which inhibited the phagocytic activity of lung macrophages, for example, sera from such mice inhibited lung colloid trapping when injected into new hosts. I.p. administration of Biostim, however, resulted in the appearance of factors in the blood which enhanced phagocytosis of lung macrophages. Our conclusion is that the biological activity of Biostim in vivo may be highly dependent on its route of administration. PMID- 8505149 TI - CD4-binding compounds: an assay to detect new classes of immunopharmacological agents. AB - The interaction of antibodies with protein antigens is accepted as a paradigm of protein-protein interactions. In searching for a new generation of immunomodulatory compounds based on the interaction of the T-cell surface glycoprotein CD4 with MHC class II antigens, a model assay has been developed in which MHC molecules have been substituted by a monoclonal antibody (anti-Leu3a) to the CD4 amino-terminal domain-specific epitope, Leu3a. This assay can detect diverse classes of molecules including proteins such as HIV envelope glycoprotein gp120 and low molecular weight compounds such as aurin tricarboxylic acid, dextran sulphate and Evans blue. The interaction of these molecules with CD4 in the assay appears to be identical to their interaction with native CD4 on intact cells. Other protein-antibody pairs could be substituted for CD4-anti-Leu3a enabling this assay format to be used for the detection of proteins or small organic compounds which interfere with a wide range of therapeutically-relevant macromolecular interactions. PMID- 8505150 TI - Cellular immune responsiveness in rabbits with Setaria digitata filarial antigen and TDM adjuvant. AB - The purified surface antigens of the bovine filarial parasite Setaria digitata were used as an antigen to immunize rabbits. The aqueous suspensions of trehalose 6-6' dimycolate (TDM) has been successfully used as an effective immunomodulator in experimental studies on filariasis. The effectiveness of such an antigen-TDM combination was demonstrated by enhanced humoral and cellular immunity. Administration of antigen alone shows only humoral immunity. The detectable cellular immune responses further confirm the effect of filarial antigen-TDM combination. The cell-mediated immunity was expressed in vivo by delayed skin reaction and in vitro by leukocyte and macrophage migration inhibition tests. PMID- 8505151 TI - The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-alpha production by human mononuclear cells. AB - Compounds suppressing the production of tumor necrosis factor-alpha are protective in animal models of septic shock. Recent studies demonstrated a beneficial effect of xanthine derivatives, which suppress tumor necrosis factor alpha production by acting as non-specific cAMP phosphodiesterase inhibitors. In this experiment we tested the effect of (+/-)-rolipram (racemate) and its enantiomers on human mononuclear cells stimulated with lipopolysaccharide (LPS). Rolipram has a phenyl-pyrrolidinone structure, unrelated to the methylxanthines, and acts as a specific inhibitor of the type IV phosphodiesterase. Our results identify rolipram as a remarkably potent suppressor of the LPS-induced synthesis of tumor necrosis factor-alpha. When compared to the non-specific inhibitor pentoxifylline, the IC50 of (+/-)-rolipram (130 nM) is more than 500 times lower. The influence of rolipram on tumor necrosis factor-alpha production depended on the steric configuration of the molecule, since the (-)-enantiomer exhibited a five times lower IC50 than the (+)-enantiomer. The inhibitory effect of all substances tested is selective for tumor necrosis factor-alpha rather than interleukin-1 beta, since interleukin-1 beta production is only slightly influenced. PMID- 8505152 TI - Reversal of inhibition of reactive oxygen species on respiratory burst of macrophages by polysaccharide from Coriolus versicolor. AB - Using a luminol-dependent, chemiluminescence assay we found tert butylhydroperoxide to be a strong inhibitor of the respiratory burst of mouse peritoneal macrophages. However, the inhibition of respiratory burst induced by tert-butylhydroperoxide could be prevented after the interperitoneal injection of polysaccharide from Coriolus versicolor (PSK). Further investigation showed that glutathione peroxidase activity was markedly elevated in PSK-treated macrophages. After incubation with tert-butylhydroperoxide, higher activity of glutathione peroxidase was maintained in PSK-treated macrophages. These results suggest that the immunological function of macrophages is related to the activity of glutathione peroxidase. The non-specific immunopolysaccharide might protect macrophages from the damage induced by reactive oxygen species by enhancing antioxidative capacity. PMID- 8505153 TI - Immunotoxicity of in vitro vanadium exposures: effects on interleukin-1, tumor necrosis factor-alpha, and prostaglandin E2 production by WEHI-3 macrophages. AB - Treatment of cultured mouse macrophages with either of two different vanadium compounds was shown to affect the production/release of two major immunoregulatory cytokines. The pentavalent vanadium compound ammonium metavanadate was shown previously to disrupt cell-mediated immunity at the earliest stages of an in vivo anti-Listerial response, in that mice treated with vanadium displayed decreased accessory cell recruitment and numbers of activated macrophages at infection sites. To determine whether these effects were due to vanadium-induced alterations in the production of biologically-active mediators, mouse macrophage-like WEHI-3 cells were treated in vitro with ammonium metavanadate or vanadium pentoxide prior to stimulation with lipopolysaccharide endotoxin (LPS). After stimulation, monokine (tumor necrosis factor-alpha and interleukin-1) and prostaglandin E2 (PGE2) activities were assessed. Both vanadium compounds decreased recovered monokine activities; measured TNF alpha concentrations were also reduced. Spontaneous release of the IL-1/TNF-regulating prostanoid PGE2 was significantly increased by the highest concentration of vanadate tested, although LPS-stimulated PGE2 production was unaffected by either compound. These results indicate that, in vitro, pentavalent vanadium can interfere with immunoregulatory mediators critical for maintaining host immunocompetence. PMID- 8505154 TI - Changes in free amino acids in peripheral blood (PB) lymphocytes and polymorphonuclear (PMN) leukocytes after treatment with diazepam. AB - The effect of single and chronic (15 days) i.p. injections (1.0 and 8.0 mg/kg) of diazepam (DZ) on free amino acid profile in peripheral blood (PB) lymphocytes and polymorphonuclear (PMN) leukocytes of male Wistar Albino rats were investigated. Depletion of some free amino acids was observed in the lymphocytes (mixed T- and B-lymphocytes) and PMN leukocytes (91-95%) neutrophils especially after chronic DZ-treatment. A dose-dependent depletion in the lymphocyte amino acids, Tau, Gly, Ala, Met and Ile, was found after both acute and chronic DZ-treatment. A similar depletion of Tau, Asp, Glu and Met appeared in the PMN leukocytes after single doses as well as chronic DZ-treatment. These results suggest that administration of 1.0-8.0 mg/kg of DZ in single dose or after chronic administration may interfere with the transport of certain important amino acids and/or protein turnover in PB lymphocytes and PMN leukocytes. On the other hand, the basic amino acids Lys, His and Arg were significantly increased in PMN leukocytes after chronic administration of 1.0 mg/kg DZ. It was suggested that the increased levels of the basic amino acids in the neutrophils may interact with the intracellular changes in pH that normally accompany the respiratory burst. PMID- 8505155 TI - Dermatophyte infections. PMID- 8505156 TI - Lobomycosis. PMID- 8505157 TI - Psoriasis, involucrin, and protein kinase C. PMID- 8505158 TI - Telogen effluvium: an etiopathogenetic theory. PMID- 8505159 TI - Microcystic adnexal carcinoma: in vitro growth characteristics and effect on stromal collagen production. AB - BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive cutaneous neoplasm, which is characterized by follicular and sweat gland differentiation and a stroma of dense collagen. METHODS: MAC cells were studied and characterized in vitro through phase microscopy and proliferation assays. Additionally, to delineate a possible role of soluble mediators in bringing about the dense stromal collagen seen in association with these tumors, the effect of conditioned media derived from the tumor cells on the level of collagen production by normal fibroblasts was examined. RESULTS: A significant morphologic difference between the MAC cells and normal keratinocytes was not noted. Proliferation assays demonstrated a significantly slower rate of growth of the MAC cells in comparison to controls. Media conditioned by MAC cells did not induce an increase in collagen synthesis by cultured fibroblasts, but rather, there appeared to be an inhibitory effect on the level of collagen synthesis. CONCLUSIONS: The increased stromal collagen seen in MAC histologically is not the result of growth factors or cytokines produced by the MAC cells. PMID- 8505160 TI - Primary Merkel cell tumor: a clinical analysis of eight cases. AB - BACKGROUND: In recent years, an unusual biologic behavior of Merkel cell tumor (MCT) has been noted. In some patients, the tumor was indolent and well controlled by therapy, while in others it was lethal in a few months. Even though the majority of the reported cases are between these two biologic extremes, it seems evident that there is a high variability in the clinical course of the tumor. METHODS: A clinical analysis of eight cases of primary Merkel cell tumor was performed. All the patients presented with similar clinical features: age, tumor staging, duration of the disease, lack of complicating cutaneous or systemic diseases. On the basis of these common findings, which made this group quite homogeneous, our attempt was to identify other clinical signs that could correlate with the local recurrence and/or the onset of metastases. The outcome of our patients, in fact, was quite variable. RESULTS: The tumor size, the clinical aspect at presentation (single, multiple nodules, or plaque), the histologic pattern (all were of the trabecular type), and immunohistology did not correlate with the outcome. CONCLUSIONS: We report the rare occurrence of MCT in the perianal area, which suggests that it should be included in the differential diagnosis of perianal tumors, the very aggressive behavior of the tumor in two patients (death < 6 months from diagnosis), which confirms how the prognosis for MCT is unpredictable even if the diagnosis is established at an incipient stage and the tumor promptly removed. PMID- 8505161 TI - Significance of pre-existent conditions in basal cell carcinoma on the lower extremities. AB - BACKGROUND: Basal cell carcinoma (BCC) rarely appears on the lower extremities; over 85% appear on the head and neck. CASE REPORTS: Five patients had BCC on the lower extremity. Histologically, this was of the superficial type. One patient developed a lesion of actinic keratosis. RESULTS: The presence of pre-existent cutaneous changes of BCC arising on the lower extremities was studied. Among 40 tumors reported in Japan, 10 cases (25%) had pre-existent cutaneous changes. This value is significantly higher than those of BCC over the whole body in both Japanese and Caucasian. CONCLUSIONS: Pre-existent cutaneous changes, thus, are thought to be a possible etiologic factor in the pathogenesis of BCC on the lower extremities. PMID- 8505162 TI - Spitz nevus. AB - BACKGROUND: The Spitz nevus is a rare form of benign nevus, which may be confused with malignant melanoma. METHODS: We reviewed the clinical and histologic features of 29 cases of Spitz nevus, of which 20 were dealt with by our department of dermatology at the Hull Royal Infirmary between 1969 and 1990. The other nine cases were from the records of our pathology department dated between 1979 and 1991, of which seven of the lesions were excised by the surgeons and two by the general practitioners. RESULTS: In all the cases, the final diagnosis was established histologically. In three cases, there were difficulties histologically in excluding the diagnosis of malignant melanoma. All the lesions were solitary, and none of the lesions recurred following excision despite the possibility of incomplete excision in some cases. CONCLUSIONS: We found the size of the lesion and the age of the patient important factors to consider in the diagnosis of Spitz nevus. The small number of cases we encountered over a period of 22 years in a department that serves a population of around 500,000 emphasises the rarity of the condition. PMID- 8505163 TI - Angiolymphoid hyperplasia with eosinophilia of the lower lip. PMID- 8505164 TI - Treatment of lentigo maligna with azelaic acid. PMID- 8505165 TI - Successful treatment of acne vulgaris in women with a new topical sodium sulfacetamide/sulfur lotion. PMID- 8505166 TI - Mesoglycan treatment restores defective fibrinolytic potential in cutaneous necrotizing venulitis. AB - BACKGROUND: Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (CFA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced CFA and PFA cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition. METHODS: We have studied both the PFA and CFA potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan. RESULTS: Cutaneous fibrinolytic activity and CFA potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (DIF) showed similar findings before and after treatment. CONCLUSIONS: These data suggest that reduced CFA may play a major role in the pathogenesis of the immunologically mediated injury in CNV. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolytic activity (or potential) the use of a fibrinolytic agent should be considered. PMID- 8505168 TI - Tattoo removal: tannic acid method of Variot. AB - BACKGROUND: There are many methods for tattoo removal (e.g., surgery, cryosurgery, laser, dermabrasion), but none can restore the skin to its original state. METHODS: Tattoo removal was obtained with a combination of tattoo machine, tannic acid, and silver nitrate. RESULTS: This technique proved to be effective for the removal of amateur tattoos of any size. The results with professional tattoos were much less satisfactory. The estimation of the depth of pigment in pretreatment biopsies showed no correlation with the success rate of treatment. No indication of systemic side effects on the liver from tannic acid was found in the concentration and amount used in this study. CONCLUSIONS: This technique is effective for the removal of amateur tattoos of any size and is comparable with cryotherapy, infrared coagulation, and focal salabrasion. PMID- 8505167 TI - Cosmetic tattooing as a treatment of port-wine stains. AB - BACKGROUND: Medical treatment for port-wine stains frequently is cosmetically unsatisfactory. An alternative possibility is cosmetic medical tattooing. METHODS: By means of a traditional Japanese tattooing technique, five patients were treated in multiple sessions until the color of the lesion matched that of the surrounding skin. RESULTS: The results were excellent, the skin texture remained normal, and the patients could discontinue cosmetic camouflage. DISCUSSIONS: Cosmetic medical tattooing when carefully done is a valuable addition to the medical armamentarium and may replace more aggressive techniques. PMID- 8505169 TI - Tattooing and its medical aspects. PMID- 8505170 TI - Linear and whorled nevoid hypermelanosis. PMID- 8505171 TI - UVA and interferon-alfa therapy in a patient with lichen planus and chronic hepatitis C. PMID- 8505172 TI - Occupation and cancers of the lung and bladder: a case-control study in Bombay. AB - Associations between occupation and cancers of the lung (n = 246) and bladder (n = 153) were examined in a case-control study. Controls (n = 212) comprised cases of oral (75%) and pharyngeal cancers (13%) and non-neoplastic oral diseases (12%) at the same hospital. Only males were studied. A personal interview was conducted and a lifetime occupational history and information on demographic and relevant confounding factors including tobacco use were obtained. For lung cases, comparing 'ever' employed with 'never' employed in a particular occupation, significantly elevated risks (adjusted for smoking) were found for textile workers (odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.3-3.6) and cooks (OR = 4.48, 95% CI: 1.2-16.9). High risks were also observed among ship and dockyard workers (OR = 2.87, 95% CI: 0.8-10.1) and wood workers (OR = 2.88, 95% CI: 0.9-9.6). For bladder cancers, significantly elevated risk was observed only for chemical/pharmaceutical plant workers (OR = 4.48; 95% CI: 1.2-16.5). Two other sets of risk estimates were obtained: one by comparison with a second unexposed group made up of occupations where there was little likelihood of exposure to any cancer-causing occupational agent, and the other by fitting logistic regression models to the data. All methods yielded similar risk estimates. Tobacco smoking but not tobacco chewing was a risk factor for both sites. PMID- 8505173 TI - Lactation and the risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. AB - The relationship between lactation and the development of epithelial ovarian cancer was assessed in data from seven countries that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. Three hundred and ninety-three cases of ovarian cancer were compared to 2565 controls matched on age, hospital, and year of interview. A non-significant reduction in risk with short-term lactation was observed but no further reduction in risk was seen with long-term lactation. The reduction in risk associated with months of lactation was not as great as the reduction with months of pregnancy, which may be a result of lactation being a less effective form of ovulation suppression than pregnancy. The short-term lactation that takes place in developed countries, may provide as great a reduction in risk as the long-term lactation practised in the developing countries included in this study. PMID- 8505174 TI - Small bowel cancer in western Canada. AB - Based on incident cases of small intestinal cancers in the four western Canadian provinces reported in the population-based cancer registries of British Columbia, Alberta, Saskatchewan and Manitoba we evaluated the descriptive epidemiological characteristics such as age, sex and subsite distribution of adenocarcinomas, carcinoids, lymphomas and sarcomas for the period 1975-1989. The distribution of adenocarcinomas, carcinoids and lymphomas presented a clear trend along the length of the small bowel. Most of the adenocarcinomas (54.7%) occurred in the duodenum and their relative frequency decreased in aboral direction: 29.9% in the jejunum and 16.0% in the ileum. The carcinoids showed an opposite trend, an increasing relative frequency in aboral direction: 3.9% in the duodenum, 9.2% in the jejunum and 86.7% in the ileum. Lymphomas were more frequent in the ileum (49.5%) compared to jejunum (29.4%) and duodenum (21.0%). Most sarcomas occurred along the jejunum (46.7%). The mean and median ages of lymphoma and sarcoma patients were significantly lower compared to adenocarcinoma and carcinoid cases. There was no difference in mean and median age by gender in the adenocarcinoma and carcinoid categories, but in the lymphoma and sarcoma groups males were significantly younger than females. PMID- 8505175 TI - Dietary sugar intake in the aetiology of biliary tract cancer. AB - Although gallstones and obesity are important risk factors for biliary tract cancer, the relation between diet and this type of cancer has not been studied in detail. Between 1984 and 1988 we conducted a case-control study of 111 cases of biliary tract cancer and 480 controls from the general population. Food intake was assessed by means of a semiquantitative food frequency questionnaire. Estimates of the total energy intake and the intake of macronutrients were obtained from the patients and controls themselves (direct respondents) or from relatives (indirect respondents). The major finding is that the risk associated with the intake of sugars (i.e. the combined intake of monosaccharides and disaccharides), independent of other sources of energy, is more than doubled for indirect respondents and for both respondent groups combined. A biological explanation for the fact that the intake of sugars may be a risk factor for biliary tract cancer might be based on the relationships between sugar, blood lipids and gallstone formation. PMID- 8505176 TI - Working hours and ischaemic heart disease in Danish men: a 4-year cohort study of hospitalization. AB - Four groups of men with non-daytime work were identified in two surveys. The relative risk of being admitted to hospital due to ischaemic heart disease (IHD) (ICD-8, 410-414) was measured in a 4-year cohort study of all 1,293,888 economically active men in Denmark, aged 20-59 years. Compared with occupational groups having day-work only, men in occupations with frequent night and early morning work had an excess standardized hospitalization ratio (SHR) of 193, occupational groups with late evening work had an excess SHR of 216, groups working in rosters covering 24-hour services had an excess SHR of 174, and groups having other irregular working hours had an excess SHR of 172. We conclude that night work rather than shifts is responsible for a raised risk of IHD. More research is needed to develop preventive strategies. PMID- 8505177 TI - Sensitivity and specificity of the initial working diagnosis in acute myocardial infarction: implications for thrombolysis. AB - Diagnosing acute myocardial infarction promptly allows all eligible patients to be considered for thrombolysis. Objective evidence from the first electrocardiograph may be inadequate and often the doctor must base his immediate management on limited information; an incorrect initial working diagnosis might deny some patients the benefits of thrombolysis or expose others to inappropriate, expensive and potentially harmful treatment. We were interested to find out how accurate our junior doctors were in their assessment of patients admitted with a suspected MI. All patients entered onto the Nottingham Heart Attack Register admitted with suspected acute MI from 1982 to 1986 and 1989 were identified. The initial working diagnosis on admission was obtained from the patient case record. A final diagnosis was assigned according to strictly defined criteria using 'cardiac' enzyme and electrocardiographic results. Sensitivity and specificity of the initial working diagnosis was calculated. Using the initial working diagnosis as a 'screening' test, we found that, while our doctors successfully identified patients with myocardial ischaemia, they were less good at recognizing acute MI--an admission diagnosis of 'MI' carried a sensitivity of 55% and specificity of 88%. This may explain the low utilization of thrombolysis in the Nottingham hospitals. In the first full year since thrombolysis became available, we estimated that we might have exposed 65 patients to the risks of thrombolysis inappropriately and we might have missed treating 244 patients. PMID- 8505178 TI - Dietary and lifestyle determinants of mortality among German vegetarians. AB - Lifestyle characteristics of a cohort of 1904 Germans adhering mainly to a vegetarian diet were examined in relation to their mortality after 11 years of follow-up. Poisson regression modelling was performed to consider the simultaneous effects of different variables on mortality from all causes, cancer (ICD 140-208) and cardiovascular diseases (ICD 390-459). Compared to a low level of self-reported physical activity, those with a medium or high level of activity experienced only half the mortality from all causes and from cardiovascular diseases. Physical activity showed no beneficial effect for cancer mortality in this cohort. The body mass index (BMI) was an independent risk factor for mortality among men but essentially unrelated to mortality among women. Those in the middle third of the BMI distribution experienced the lowest mortality. A negative association between BMI and cancer mortality lost statistical significance when the first 5 years of follow-up were deleted, suggesting that a lower BMI was a consequence of prevalent disease. Both the duration of vegetarianism and the vegetarian status (strict versus moderate) showed a moderate effect on all cause and cancer mortality. A longer duration of vegetarianism (> or = 20 years) was associated with a lower risk, pointing to a real protective effect of this lifestyle. A lower risk of death among moderate vegetarians suggests that sound nutritional planning may be more important than absolute avoidance of meat. PMID- 8505179 TI - Serum retinol, beta-carotene, alpha-tocopherol and cholesterol in healthy French children. AB - Age- and sex-specific reference intervals of data derived from a healthy paediatric population are presented for retinol, beta-carotene, alpha-tocopherol, cholesterol and related proteins in serum. Age was an important covariate for the micronutrient concentration values. Retinol was highly correlated with alpha tocopherol and cholesterol. Strong correlation was found with both beta-carotene and cholesterol. Serum levels were considered for their appropriateness as indicators of micronutrient status. PMID- 8505180 TI - Differences in serum lipids in Australian children: is diet responsible? AB - A total of 5211 schoolchildren aged 10-15 years participated in an Australia-wide sample survey conducted in 1985 and completed dietary and demographic assessment, and the measurement of body mass index: 1017 children aged 12 and 15 years gave blood for serum lipid analysis. Group mean differences in serum lipids and body mass index with age, sex, socioeconomic status and ethnic origin were determined. Nutritional analysis generated group mean values for daily energy intake, per cent kilo-joules from total fat, saturated fat, monosaturated fat and polyunsaturated fat, as well as the polyunsaturated:saturated fat ratio and nutrient density of fibre. In multiple regression analyses, socioeconomic and gender based differences in serum lipids could be explained by differences in diet, whereas age group differences could not. Although there were statistically significant differences in dietary fat intake on the basis of ethnic origin, these were not reflected in differences in serum lipids. For girls, dietary fat variables were more important predictors of serum lipids than body mass index. For boys, the reverse was true. These results suggest that class differences in cardiovascular risk arise from dietary differences that are present from an early age. Sex-based differences in serum lipids seem to reflect different mechanisms in girls and boys. In the former, dietary differences are of importance but for the latter, anthropomorphic (possibly exercise-linked) differences are the most important. These findings imply that cardiovascular risk preventive programmes for children need to take into account the mechanisms of social inequality and sex-based differences. PMID- 8505181 TI - Social class differences in mortality from diseases amenable to medical intervention in New Zealand. AB - Social class differences in mortality from causes of death amenable to medical intervention were examined. All deaths in New Zealand males aged 15-64 years during the periods 1975-1977 and 1985-1987 were identified. Strong social class gradients in mortality from causes of death amenable to medical intervention were observed during both periods. Furthermore, social class inequalities were more pronounced for amenable causes of mortality than for non-amenable causes. However, a marked decline in the age-standardized mortality rate from amenable causes was observed, with the rate falling by 30% over the 10-year study period. This decline was twice as large as the drop in the non-amenable mortality rate. Despite the fall in the death rate from amenable causes, social class inequalities in mortality persisted among New Zealand men, with the lowest socioeconomic group experiencing a death rate from amenable causes of mortality that was 3.5 times higher than men in the highest socioeconomic group. PMID- 8505182 TI - Risk of childhood type 1 diabetes for Russians in Estonia and Siberia. AB - We have compared the incidence of Type 1 diabetes in childhood between two predominantly Russian populations from the former Soviet Union--the non-Estonians living in Estonia and the inhabitants of the district of Novosibirsk. The study period covered the years 1980-1989 for the non-Estonians and 1983-1989 for the district of Novosibirsk. The mean annual incidence of Type 1 diabetes was significantly higher in the non-Estonian population, 7.8 per 100,000 (95% confidence interval (CI): 6.3-9.6) than in Novosibirsk where it was 4.7 per 100,000 (95% CI: 4.1-5.4). The highest incidence in females from Estonia was in the age group 5-9 years and in Novosibirsk 10-14 years. In the youngest age group of 0-4 years there was no difference in the incidence between non-Estonians in Estonia and the population of Novosibirsk, or males and females in either population. There was no difference in the incidence between the 0-4 and 5-9 year age groups in Novosibirsk males. No time trend was seen in the incidence over the study period in either population. The annual incidence in Novosibirsk was fairly stable, while in the non-Estonians it showed two distinct peaks. The most likely reason for the observed phenomena is a different pattern and higher prevalence of environmental causal agents in the Baltic country of Estonia. PMID- 8505183 TI - Risk indicators for inflammatory bowel disease. AB - We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives. PMID- 8505184 TI - Risk factors for overdose mortality: a case-control study within a cohort of intravenous drug users. AB - Overdose mortality is the major adverse health effect of drug injection. The potential determinants of overdose death are poorly understood; the aim of this study was to investigate risk factors for overdose mortality among intravenous drug users (IVDU). A cohort of 4200 IVDU attending methadone treatment centres in Rome during the period 1980-1988, was enrolled. Data were collected from clinical records. Vital status and cause of death were ascertained as of 31 December 1988. A matched case-control analysis within the cohort was performed to identify risk factors of death from overdose. All overdose deaths were included as cases and four controls, matched on year of birth and sex, were selected for each case from among the cohort members still alive at the time of death of the corresponding case. In all, 81 deaths from overdose were identified as cases and compared with 324 controls. A high risk of overdose death occurred among subjects who left treatment compared with those still in treatment (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.82-6.90). The OR was particularly elevated in the first 12 months after drop-out compared with those retained in treatment (OR = 7.98, 95% CI: 3.40-18.73). The risk of overdose death was higher for unmarried compared with married people (OR = 2.48, 95% CI: 1.31-4.68); a higher risk of overdose death was also associated with lower educational status and younger age at first drug use, but such association was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505185 TI - Risk factors for clinical marasmus: a case-control study of Bangladeshi children. AB - A case-control study of risk factors of clinical marasmus was undertaken to guide intervention efforts in rural Bangladesh. Cases were children whose mid-upper arm circumference measured < 110 mm and controls were children matched for age and sex with arm circumference > 120 mm. Between June 1988 and June 1989, 164 such pairs of children aged 1-4 years were studied. The effects of various demographic, socioeconomic, environmental, and health factors, reported by mothers, were investigated in a multivariate analysis using conditional logistic regression. Results showed an increased risk of marasmus among children from families with other children under 5 years of age (odds ratio [OR] = 2.51; 95% confidence interval [CI]: 1.33-4.74), and children who consumed formula foods (OR = 16.41, 95% CI: 3.39-79.36). Higher maternal education was associated with reduced risk of marasmus, compared with no education, the OR for < 5 years of schooling = 0.57, 95% CI: 0.23-1.41; OR for > or = 5 years of schooling = 0.34, 95% CI: 0.15-0.76. The strong association of childhood marasmus with mother's education and child spacing supports the notion that non-nutritional factors should be essential components of efforts to reduce severe malnutrition in Bangladesh. PMID- 8505186 TI - Prevalence of hand dermatitis in different occupations. AB - The prevalence of hand dermatitis in different occupational groups was estimated using a standardized questionnaire in a series of surveys among workers of a chemical company, a municipal electricity company, municipal public works, nurses and surgical assistants. A survey in a sample of the general population was performed to obtain a reference estimate of the prevalence. The prevalence of hand dermatitis in the general population was 5.2% in men and 10.6% in women. The prevalence of hand dermatitis among the occupational groups ranged from 2.9% in office workers to approximately 30% in nurses. The age-adjusted prevalence ratio (PR) of hand dermatitis in office workers was not significantly elevated compared with the general population. In nurses, the age-adjusted PR was 9.3 among men (95% confidence interval [CI]: 3.6-23.9) and 2.2 among women (95% CI: 1.5-3.5). The PR in surgical assistants was not significantly elevated (PR = 1.4, 95% CI: 0.7-2.6). This suggests that exposure in nurses (frequent washing of the hands), is more harmful to the skin than the less frequent but more intensive exposure in surgical assistants. The age-adjusted PR were also significantly elevated in male manual workers of the chemical company, the electricity company and public works and varied from 2.4 to 2.8. Occasional or regular occupational exposure to a variety of irritants in combination with mechanical stress (as occurs frequently in manual work) may be responsible for this observation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505187 TI - The aetiology and risk factors for warts among poultry processing workers. AB - We conducted an investigation at a poultry processing plant in New Zealand to estimate the prevalence of warts among workers and the risk of developing warts associated with specific work areas or individual work practices. We obtained information on demographic characteristics and self-reported medical and occupational histories from 88 (83%) of 106 permanent employees at the plant; almost half (39 people or 44%) had developed wart-like lesions on their arms or hands after they began working at this plant. We also conducted clinical evaluations of 28 of the 32 (88%) people with wart-like lesions at the time of the investigation; in all but one case, a diagnosis of warts was confirmed. We collected scrapings of warts from 22 (79%) people and identified human papillomavirus (HPV) type 7, which is reportedly uncommon in the general public, in 12 of these specimens. People working at the time of their interview in areas where they often handled dead, raw, unfrozen chickens were three times more likely to have developed warts (Odds ratio [OR] = 3.0, 95% confidence interval [CI]: 1.2-8.0); for those who had ever worked in these 'high-risk' areas, this excess risk almost doubled (OR = 5.6, 95% CI: 2.1-14.7). Nine of the 12 (75%) people with HPV type 7 had worked in these areas at some time. In contrast to previous reports, we found no increased risk of having warts associated with environmental factors or the frequency of cuts and abrasions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505188 TI - The incidence of child sexual abuse in Northern Ireland. AB - This is part of a major epidemiological survey of the reported incidence (new cases) of child sexual abuse in Northern Ireland. Based on multi-source methodology, the study used computer-based record linkage techniques to find the number of incident cases occurring in the Province in 1987. Reporters involved with the incident cases were interviewed by OEV who recorded details of the child, the abuse, and the abuser using a specially designed questionnaire. Age sex specific incidence rates adjusted for potential misclassification were computed and allowance made for under-ascertainment. Overall, 408 Established cases were reported during 1987. The corresponding incidence rate for Northern Ireland was 0.9 cases per 1000 children. When Suspected and Alleged cases were compared with Established cases, a further 119 cases were allocated by discriminant function analysis to the Established group, and the rate rose to 1.16 per thousand. Selected reporters were interviewed about ascertainment which was estimated to lie between 62% and 74%. If the lowest level of ascertainment applied the corresponding incidence rate for Northern Ireland would increase to 1.87. These figures are higher than those currently reported elsewhere in the UK, but methodological differences in study design hamper interregional comparisons. A number of relevant methodological problems are discussed. PMID- 8505190 TI - Differences in mortality rates and causes of death between HIV positive and HIV negative intravenous drug users. AB - In order to study differences in mortality and causes of death between HIV positive and HIV negative intravenous drug users (IVDU), 1009 (180 HIV positive and 829 HIV negative) IVDU in Oslo, Norway, were followed from their first HIV test for a mean period of 36 months (range 1-67 months). Eighty-seven (55 HIV negatives and 32 HIV positives) died during the follow-up period. The risk of death for IVDU was 31 times higher than for the general population. The estimated probability of survival after 3 years of follow-up was 0.92 for the whole cohort, 0.93 for the HIV negative group and 0.87 for the HIV positive group (P < 0.001, log rank test). In a Cox regression analysis, HIV positivity, > 30 years of age and > 5 years of IV drug use prior to study entry were all significantly associated with a fatal outcome. Eleven per cent (n = 20) of the HIV positives and 4% (n = 38) of the HIV negatives died from drug overdose, which accounted for 68% of all deaths; 2.2% of the HIV positives and 0.4% (n = 4) of the total cohort died from AIDS. Drug overdose represented the major threat to life among IVDU in this study. Because of the dynamics of the HIV epidemic, AIDS may have an increasing impact on mortality. However, in order to forecast the number of AIDS cases among IVDU the high non-AIDS mortality must be controlled for. PMID- 8505189 TI - Geographical variations in the prevalence of HIV infection among drug users receiving ambulatory treatment in Spain. AB - To identify the factors responsible for the regional differences in HIV-positive serostatus among drug users in Spain receiving outpatient treatment, the 17 autonomous regions into which Spain is divided were classified as high (mean 52%) or low prevalence groups (mean 34%) depending on the prevalence of seropositivity. In regions where the prevalence of positive serostatus was high, unemployment was more markedly associated with HIV infection than in low prevalence regions, while other potential risk factors yielded the same strength of association. Even so, adjustment for all the factors only accounted for 13% of the total difference in HIV+ prevalence between regions. The current distribution of risk factors among the two groups of autonomous regions does not explain these differences. PMID- 8505191 TI - Evaluating modifications in epidemic surveillance systems: a method and an application to AIDS surveillance in Switzerland. AB - A method is presented for evaluating the impact of a modification in a surveillance system for an epidemic disease among reporting sources susceptible to the modification. The approach requires a control series with reports from sources that are not affected by the modification. The measure of effect is the reporting odds ratio (ROR) which estimates the ratio of reporting proportions (completeness) before and after the change. The proportions themselves remain unknown. Various potential biases are identified and an investigation of one potential bias is proposed. The method may prove useful in supplementing techniques that estimate absolute values of completeness of registry systems. The application to AIDS surveillance data in Switzerland shows that the transition from voluntary to mandatory reporting had an impact that was enhanced by the 1987 revision of the Centers for Disease Control case definition for AIDS. Reporting sources were 1.9 (95% confidence interval [CI]: 1.4-2.6) times more likely to report their patients after introduction of mandatory reporting. It is estimated that 15% of all reports were attributable to mandatory reporting. PMID- 8505192 TI - Maternal behavioural risk factors for severe childhood diarrhoeal disease in Kinshasa, Zaire. AB - This study examines the relationship between severe diarrhoeal disease and maternal knowledge and behaviours related to hygiene and sanitation. Some 107 paediatric cases admitted to two hospitals in Kinshasa, Zaire in 1988 were matched on age and nearest-neighbour status to 107 controls. Personal interviews and observational methods were used to assess knowledge and behaviours related to hygiene and sanitation. Cases and controls had equivalent socioeconomic status, demographic profiles and access to water and sanitation facilities. However, cases generally exhibited lower levels of knowledge and less sanguine sanitary practices than did controls. Of particular interest was the finding that very specific behavioural items distinguished cases from controls. The disposal of the child faeces and household garbage and mother's knowledge that poor caretaker cleanliness was a cause of diarrhoea in children showed the strongest associations with risk of diarrhoea. There was an exponential relationship between the number of these items a mother answered incorrectly and the odds of diarrhoeal disease. The risk attributable to these three variables was as high as 70%. These findings provide further support for the view that focused educational interventions may have a substantial impact on the occurrence of severe diarrhoeal disease in low-income countries. PMID- 8505193 TI - Impact of influenza on mortality in relation to age and underlying disease, 1967 1989. AB - Based on data from the Dutch Central Bureau of Statistics, the impact of influenza on mortality in The Netherlands was estimated for a 22.5-year period (1967-1989) in four age groups and three entities of disease, using Poisson regression techniques. Our analysis suggests that, on average, more than 2000 people died from influenza in The Netherlands each year, but in only a fraction of these deaths was influenza recognized as the cause of death. For each case of death registered as caused by influenza (registered influenza mortality), 2.6 additional cases of death registered as due to causes other than influenza, nevertheless, were influenza-related (non-registered influenza mortality). Therefore, the overall impact of influenza on mortality is estimated to be greater than registered influenza mortality by a factor of 3.6. Those under 60 years of age accounted for 5% of all non-registered influenza deaths, whereas people aged 60-69, 70-79 years and > 80 years accounted for 12%, 29% and 54% of such deaths, respectively. When extrapolating the figures for the Dutch population of 1989, we could attribute, on average per season-year, 82 deaths per 100,000 people > 60 years, 143 in people > 70 years, and 280 in people > 80 years. Of all non-registered influenza cases of death, 47% were estimated to occur in people with heart disease as a primarily reported cause of death, 23% in those with lung disease, and 30% in those with other diseases. This study stresses the serious effects of influenza, mainly in the elderly (95% of non registered influenza mortality).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505194 TI - Risk factors for trichiasis in women in Kongwa, Tanzania: a case-control study. AB - Women are at a greater risk compared to men for blinding complications from trachoma. In order to evaluate risk factors in women, 205 cases of trichiasis (TT) were selected from 11 villages in rural Tanzania. Each case of trichiasis was matched to two women of the same age and from the same village, who had no clinical signs of trachoma. Factors associated with trichiasis in a conditional logistic regression included history of trichiasis in the women's mother (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 2.0-6.5); sleeping in a room with a cooking fire during childbearing years (OR = 1.8; 95% CI: 1.2-2.8); a home of wood and earth during childbearing years (OR = 2.1; 95% CI: 1.3-3.3); no adult education classes (OR = 2.2; 95% CI: 1.4-3.4); and five or more deaths among her children (OR = 2.6; 95% CI: 1.3-5.1). Detailed measures of prolonged exposure to child care as a young girl and as a mother showed no significant difference between cases and controls. Results from this study characterize women at high risk for severe disease and eventual blindness in a trachoma endemic area. PMID- 8505195 TI - The nutritional status of children of displaced families in Beirut. AB - The nutritional status of children of displaced families in Greater Beirut was investigated in 1986 (a sample of 146 households) and in 1991 (137 households). Data on demographic variables, nutrient intake (calories, protein, and iron), and anthropometric measurements were collected. Iron intake was only 50-57% of the RDA for the 1-3 age group, and 35.6% and 32.0% of all children consumed < 60% of the RDA for iron in 1986 and 1991, respectively. Main sources of protein were dairy products, milk and eggs. The lower nutrient intake in 1991 compared to 1986 was negatively related to social class. Anthropometric measurements showed an increased past and recent undernutrition of the children in 1991 as compared to both the 1986 child sample and the NCHS standard child population. Severe inflation and marked increase in food prices were reflected in dietary intake and growth of the children. Food aid programmes, government subsidy of bread, and partial wage correction were possible stabilizing factors for the most destitute groups but not for the total population of displaced children. PMID- 8505197 TI - Epidemiological basis of malaria control: old ideas, new directions. PMID- 8505196 TI - Space time clustering of births in SIDS. PMID- 8505198 TI - In vivo determination of the anisotropic diffusion of water and the T1 and T2 times in the rabbit lens by high-resolution magnetic resonance imaging. AB - PURPOSE: Several magnetic resonance imaging (MRI) "tools" for ophthalmologic research have recently been developed in this laboratory, including improved gradient and radiofrequency coils and pulse sequences for high-resolution and diffusion imaging (100-microns resolution). METHODS: These tools have been applied to the in vivo measurement of the relaxation parameters (T1 and T2) and the water diffusion coefficients (Dx and Dy) in the rabbit eye lens, both normal and cataractous. Maps of these parameters in the lens have been computer generated. RESULTS: In the normal lens, water diffusion is highly anisotropic and tends to be parallel to the surface. In the trauma-induced cataractous lens, an increase in spin-spin relaxation times (T2) consistent with edema and alteration of diffusion patterns was observed in a study conducted 2 weeks postsurgery. A partial reversal was observed 6 weeks postsurgery. The histologic data on the enucleated lens at 6 weeks showed a loss of normal lens architecture. Images are shown that display other small structures of the anterior segment with great clarity. CONCLUSIONS: An extension of this work, now underway, is the study of the formation of various types of cataract in animal models. It is hypothesized that these methods can be extended to humans as a quantitative alternative for the assessment of cataracts. PMID- 8505199 TI - Cytoplasmic surface ultrastructures of gap junctions in bovine lens fibers. AB - PURPOSE: To examine the cytoplasmic surface ultrastructures of lens fiber gap junctions, where the cytoplasmic domains of connexons were expected to be exposed. METHODS: Bovine lens fiber gap junctions, both in situ and in the form of isolated membranes, were examined with the deep etching replica methods. Isolated membranes were also examined with the same methods after the treatment with endoproteinase glu-C, which is known to cleave off the cytoplasmic domain of a putative lens fiber connexin MP70 to determine whether any structural changes should occur between proteolyzed and nonproteolyzed gap junctions. In addition, both proteolyzed and nonproteolyzed gap junctions were studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunolabeling with the monoclonal antibody that recognized cytoplasmic domain of MP70 to clarify whether MP70 lost its cytoplasmic domain by the treatment with endoproteinase glu-C. RESULTS: Gap junctions were shown to have particulate substructures on their cytoplasmic surfaces; the distributions of the particles were restricted within gap junctional plaques and the non-gap-junctional areas showed smooth cytoplasmic surfaces. Although the treatment with endoproteinase glu-C failed to remove the cytoplasmic particles of gap junctions in deep etching replica study, MP70 was shown to have lost its cytoplasmic domain in sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunolabeling studies. CONCLUSIONS: Each particle revealed on the cytoplasmic surfaces of lens fiber gap junctions corresponded to the cytoplasmic domain of a connexon. The particles were not removed by the treatment with endoproteinase glu-C, whereas MP70 was cleaved by the same treatment. PMID- 8505200 TI - Apparent coordination of plasma membrane component synthesis in the lens. AB - PURPOSE: This study explores the order of assembly of the lens fiber cell plasma membrane. Because the lens must synthesize most of its membrane components, our approach was to map directly the spatial distribution of cholesterol, fatty acid (reflecting phospholipid), and the main intrinsic protein, MP26, synthesis in the lens and, thereby, determine the extent to which membrane component synthesis was coordinated during fiber cell elongation. METHODS: Young rat lenses were incubated with either tritiated water as the substrate for cholesterol and fatty acid synthesis or tritiated leucine as the substrate for MP26 synthesis. We developed a simple technique for uniformly dissolving the decapsulated lens into small fractions by incubating the lens with gentle stirring in sodium dodecyl sulfate-containing buffer. Based on the protein content of each fraction and available information on the radial distribution of protein in the young rat lens, each fraction was equated to a specific percentage of the lens radius. Cholesterol was precipitated from each fraction by digitonin; fatty acids were extracted and isolated by thin-layer chromatography. The MP26 was recovered both by immunoprecipitation from each fraction with anti-MP26 polyclonal antibody and from sodium dodecyl sulfate polyacrylamide gel electrophoresis gels of intact crude membrane, which was isolated from lens fractions by dissolving the lens in a urea containing-buffer. RESULTS: The spatial distribution of incorporation of cholesterol, fatty acid, and MP26 was virtually superimposable, with essentially all the incorporation occurring in the outer 10% of the lens radius and peak incorporation occurring in approximately the outer 3-6% of the radius. CONCLUSIONS: These results indicate that the synthesis of lens membrane components is highly coordinated and imply that the plasma membrane accumulates constant proportions of cholesterol, phospholipid, and MP26 throughout the course of fiber cell elongation. PMID- 8505201 TI - Expression of type I and type III procollagen by lens epithelial cells. AB - PURPOSE: To identify the types of procollagen that are synthesized by cultured bovine lens epithelial cells and to determine what types of post-translational modifications are involved in procollagen biosynthesis and what patterns of procollagen gene expression occur in these cells. METHODS: The epithelial nature of the cultured cells was confirmed with transmission electron and phase contrast microscopy. To label collagen, primary or secondary monolayer cultures were pulsed with [3H] proline for various periods of time. Procollagens were identified by immunoprecipitation with specific antibodies, pepsin digestion, and electrophoretic separation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Procollagen messenger RNA was identified by Northern blot analysis using specific DNA probes. RESULTS: In the normal lens epithelium, cells are attached to each other by tight junctions punctuated with desmosomes. After the proteins were labeled, they were immunoprecipitated with antibodies specific to collagen precursors and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to further confirm their identification as types I and III procollagen or processed forms of these proteins. The secretion of procollagen was inhibited by treatment with 2,2'-dipyridyl and bands of underhydroxylated procollagen were observed in the cell layer after electrophoresis. The sizes of messenger RNA observed were 6.9 kb and 5.4 kb for type alpha 1(I), 5.0 kb for type alpha 2(I), and 5.3 kb for the type III transcripts. CONCLUSIONS: This is the first report that lens epithelial cells express fibrillar procollagen genes, making the lens capsule a unique ocular basement membrane. PMID- 8505202 TI - Investigation of the role of the ras protooncogene point mutation in human uveal melanomas. AB - PURPOSE: Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. METHODS: Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. RESULTS: No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. CONCLUSIONS: This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61. PMID- 8505203 TI - Studies of human uveal melanocytes in vitro: isolation, purification and cultivation of human uveal melanocytes. AB - PURPOSE: To develop the methods for isolation and cultivation of human uveal melanocytes (UM) from adult donor eyes. METHODS: After removal of the pigment epithelium, the uvea was pretreated in trypsin solution at 4 degrees C overnight, incubated at 37 degrees C with trypsin for 1 hr, then incubated with collagenase for 3 hr. Released cells were collected each hour during the incubation and cultured with F12 medium supplemented with fetal bovine serum, basic fibroblast growth factor, isobutylmethylxanthine and cholera toxin. Contaminant cells were eliminated by adding a selective cytotoxic agent, geneticin, when necessary. RESULTS: These methods provide pure melanocyte cultures with high cell yields, good viability, and rapid growth rates. UM isolated and maintained using these methods can be passaged 23 times for a period of 7 mo for more than 35 population doublings. This is comparable to results obtained with cultured neonatal dermal melanocytes and exceeds results obtained with adult dermal melanocytes cultured in media supplemented with phorbol ester, isobutylmethylxanthine, and cholera toxin. CONCLUSION: A method for isolation and cultivation of UM has been developed that yields satisfactory results. Cultured UM may be useful in in vitro studies of UM physiology and may allow development of in vitro models of the pathogenesis of uveal malignant melanoma. PMID- 8505204 TI - Effects of gamma-interferon on human trabecular meshwork cell phagocytosis. AB - PURPOSE: Gamma-interferon (G-IFN) regulates a variety of immune responses including the modulation of the phagocytic response and induction of class II major histocompatibility complex antigens. Because human trabecular meshwork (HTM) cells in culture are known to be actively phagocytic and have been shown to express class II major histocompatibility complex antigens, the effects of G-IFN on HTM cells were examined. METHODS: Confluent HTM cells were incubated in media (Dulbecco's modified Eagle's medium +10% fetal bovine serum) containing 0, 10, 50, 100, 500, 1000, or 5000 units/ml of recombinant human G-IFN for 72 hr. After incubation, the cultured HTM cells were challenged with 5 ml of media containing 1 x 10(8) fluorescein labeled microspheres/ml. Phagocytic uptake was determined by flow cytometry. RESULTS: Flow cytometric analysis of microsphere uptake shows that G-IFN inhibited HTM cell phagocytosis of microspheres in a dose-dependent fashion. At 5000 units/ml of G-IFN, phagocytosis of microspheres was inhibited by 64.5 +/- 2.4% compared to control (P < 0.007). The half maximal dose of phagocytic inhibition is < 10 units/ml. Increasing the time of G-IFN exposure from 24 to 72 hr at 10 units/ml increased the level of phagocytic inhibition from 39 to 49%, respectively. The rate of microsphere uptake was also reduced in a dose-dependent fashion. Morphologic examination after G-IFN incubation showed that HTM cells became enlarged and flattened compared to the control. Actin cytoskeletal immunofluorescence staining showed that parallel actin beams of the control cells were changed to a radical, spokelike arrangement when incubated in G-IFN. CONCLUSIONS: G-IFN is a potent inhibitor of HTM cell phagocytosis in vitro. G-IFN's effect on the actin cytoskeleton suggests that G-IFN may be disturbing the cytoskeletal organization necessary for phagocytosis. PMID- 8505205 TI - Sensitivity and specificity of optic disc parameters in chronic glaucoma. AB - PURPOSE: Optic disc parameters are commonly used for the early detection of glaucomatous optic discs. We used receiver operating characteristics (ROC) curves to illustrate the separation characteristics of different disc parameters for this purpose. METHODS: We performed computer perimetry and computerized optic disc topometry on 93 eyes of 53 subjects with glaucoma and glaucoma-related diseases. The optic disc parameters were correlated with visual field indexes, and ROC curves for the detection of glaucomatous disc changes were calculated. RESULTS: According to clinical experience, the vertical cup/disc ratio was able to identify the glaucomatous eyes the most easily, whereas the neuroretinal rim area was less helpful in this regard. In terms of the correlation of optic disc parameters with visual field indexes, the rim area was the more powerful of the two. The cup volume showed neither separation of glaucomatous from normal eyes nor correlation with visual field indexes. CONCLUSIONS: The vertical cup-to-disc ratio is the most suitable for screening purposes, whereas the rim area is more valuable for follow-up evaluation. PMID- 8505206 TI - A model to predict aqueous humor and plasma pharmacokinetics of ocularly applied drugs. AB - PURPOSE: To develop methods for constructing a pharmacokinetic model to predict the time course of aqueous humor and plasma drug concentrations after topical dosage in rabbits using the simulation program iThink (formerly STELLA; High Performance Systems, Lyme, NH). METHOD: The model was constructed in experimentally verifiable segments using previously published data on intravenous, nasal, and ocular dosage, and was used to describe the influence of prolonging precorneal retention and varying drug release rate on the ratio of drug absorbed locally to drug absorbed systemically in rabbits. RESULTS: The model developed is comprehensive; it includes precorneal kinetics, nasal absorption kinetics, and plasma kinetics. CONCLUSIONS: Such a model may be useful in designing drug delivery strategies to improve the safety of topical eye medications through minimization of systemic absorption and maximization of drug delivery to ocular tissues. PMID- 8505207 TI - Optic disc morphology in eyes after nonarteritic anterior ischemic optic neuropathy. AB - PURPOSE: Parapapillary chorioretinal atrophy, neuroretinal rim loss, and a decrease of retinal vessel diameter have been described to occur in glaucomatous eyes. This study was conducted to evaluate the frequency and degree of these signs in nonarteritic anterior ischemic optic neuropathy (AION). METHODS: We evaluated morphometrically and compared stereo color optic disc photographs of 17 patients after AION, 184 patients with primary open-angle glaucoma, and 98 normal subjects. RESULTS: The optic disc area and retinal vessel diameter were significantly smaller and the visibility of the retinal nerve fiber bundles was significantly reduced in patients after nonarteritic AION compared with that of the normal subjects. The optic disc shape, area, and form of zones alpha and beta of the parapapillary chorioretinal atrophy and the size and form of the neuroretinal rim did not differ significantly between these two groups. In the group of eyes with glaucoma, the neuroretinal rim was significantly smaller and the parapapillary chorioretinal atrophy was significantly larger than in the group of eyes with AION. Visibility of the retinal nerve fiber bundles and retinal vessel caliber did not differ statistically between the eyes with AION and those with glaucoma. CONCLUSIONS: These results indicate that the parapapillary chorioretinal atrophy is not larger in eyes after nonarteritic AION compared with normal eyes. They show that the area and shape of the neuroretinal rim, as determined planimetrically, may not markedly change after nonarteritic AION. They confirm previous reports on a small optic disc size as a risk factor for nonarteritic AION. They agree with findings of a reduced retinal vessel caliber in eyes with optic nerve damage, independently of the cause. PMID- 8505208 TI - The visual field indices in primary open-angle glaucoma. AB - PURPOSE: The distribution of sensitivity across the visual field, as determined by automated threshold static perimetry, can be summarized in terms of visual field indices. Such indices can be weighted for the variation in threshold at each eccentricity. The aims of this study were to determine the influence of the weighting factor, the relationship between the unweighted indices derived from Programs 30-2 and 24-2, and the relationship between the number of double determinations of threshold and the magnitude of the short-term fluctuation. METHODS: One visual field derived by Program 30-2 of the Humphrey Field Analyzer was selected from each of 60 consecutive patients with primary open-angle glaucoma. The first two fields from each individual patient were avoided. Unweighted visual field indices were calculated and compared with the Program 30 2 weighted indices using an assessment of agreement evaluated with respect to the 95% confidence limits of the population. RESULTS: The weighting function had no influence on the mean deviation, but it caused a slight reduction in the short term fluctuation and an elevation in the pattern and corrected pattern standard deviations. There was little difference between the indices generated by Programs 30-2 and 24-2. The short-term fluctuation increased with an increase in the number of double determinations of threshold. CONCLUSIONS: The weighting function had little clinical influence on the visual field indices. The indices derived from Programs 30-2 and 24-2 were similar, and the short-term fluctuation would better reflect the intratest variability if all available double determinations of threshold were used to calculate the index. PMID- 8505209 TI - Optical zone diameters for photorefractive corneal surgery. AB - PURPOSE: To examine the physiological optics of photorefractive corneal surgery and to study the effect on glare production of the optical zone diameter. METHODS: An optical analysis computer program was used to generate rays that define the edge of the optical zone for any given pupil size and glare-free field. RESULTS: The optical zone diameter must be based on the postoperative corneal curvature because the determines magnification of the pupil. The minimal optical zone diameter of uniform optical power was determined both for myopic and hyperopic surgery and for two values of anterior chamber depth. CONCLUSIONS: Optical zone diameters must be at least as large as the entrance pupil diameter to preclude glare at the fovea, and larger than the entrance pupil to preclude parafoveal glare. PMID- 8505210 TI - Relation of cholesterol-stimulated Staphylococcus aureus growth to chronic blepharitis. AB - PURPOSE: Many types of chronic blepharitis have been believed to be primarily microbial in origin; however, it was proposed that differences and changes in lipid composition of meibomian secretion may be the initiating factor in some of these. It was recently reported that there are two subgroups of normals, those whose meibomian secretions contain high levels of cholesterol esters and those whose secretions contain very low levels of these esters. Thus, these subgroups of normals were defined on the basis of detailed lipid analyses of meibomian secretions from individuals showing no clinical signs of chronic blepharitis. All secretions from patients in the various disease groups contain high levels of these esters. Based on previous observations that in some chronic blepharitis disease groups certain Staphylococcus species were capable of hydrolyzing cholesterol esters, the authors tested the hypothesis that the resulting cholesterol might affect growth of Staphylococcus aureus. METHODS: Staphylococcus aureus growth stimulation in Mueller-Hinton broth by cholesterol was determined by colony forming units. Growth stimulation by cholesterol and other additives was also determined by the optical density 650 nm method. Statistical analyses included analysis of variance and the Student's t test. RESULTS: Cholesterol stimulated Staphylococcus aureus growth was significant during the first 24 hr period (20% increase at 25 microM cholesterol, P < 0.02), and for the total 48 hr period (40% increase at 400 microM cholesterol, P < 0.005) when compared to the respective control. Growth stimulation, determined by OD at 650 nm, in the presence of cholesterol was significantly greater (P < 0.02) than that in the presence of either sitosterol or cholestanol when the sterol concentration was 190 microM. CONCLUSION: These results suggest that the presence and hydrolysis of cholesterol esters of meibomian secretions may contribute to the proliferation of Staphylococcus spp, especially Staphylococcus aureus, observed in some chronic blepharitis disease groups. PMID- 8505211 TI - Alkali-degraded cornea generates a low molecular weight chemoattractant for polymorphonuclear leukocytes. AB - PURPOSE: The current study was designed to determine if a polymorphonuclear leukocyte (PMN) chemoattractant is derived from alkali-degraded whole cornea and to establish a range for its molecular weight. METHODS: We utilized a collagen gel-visual chemotactic assay to quantify the directional movement of PMN exposed to alkali-degraded corneas (30 min or 24 hr). In this experiment, the sample to be tested for chemotactic activity passed through a 14,000 molecular weight cutoff membrane into a collagen gel in which resting neutrophils were suspended in a random fashion. Cell movement was videotaped and subsequently tracked by digitizing the centroid of the cells at 30-sec intervals. Computer analysis of these tracks illustrated many behavioral characteristics, including directional movement. RESULTS: Alkali-degraded whole bovine corneas produced a chemotactic response in neutrophils within 5 min. Dilution of the 24-hr sample to 1:7 yielded a significant chemotactic response. The chemotactic response of both the 30-min and 24-hr samples followed a dose-response curve. CONCLUSIONS: This agent may be one of the inflammatory mediators that trigger the early neutrophil response after an alkali-injury to the eye. PMID- 8505212 TI - Enhanced healing of cat corneal endothelial wounds by epidermal growth factor. AB - PURPOSE: The authors investigated whether healing of cat corneal endothelial wounds could be enhanced in vivo by human epidermal growth factor (EGF). METHODS: EGF was administered in sodium hyaluronate to the anterior chamber of cats after an endothelial touch injury. Control contralateral eyes received sodium hyaluronate alone. At selected times after injury, the corneas were evaluated for thickness, the rate of endothelial wound closure, the endothelial cell density, any variation in cell size, the percentage of hexagonal cells, and endothelial cell mitosis. RESULTS: Two days after injury, endothelial wounds of eyes treated with EGF had healed an average of 65 +/- 4% of the initial 38.5 mm2 wound area; paired control eyes had healed an average of 59 +/- 4% (P < 0.05). Both EGF treated and control wounds had resurfaced over 90% of the initial wound area on day 4 after injury, and the wounds were completely resurfaced by 7 and 14 days after injury in both treatment groups. On days 4 and 7 after injury, the EGF treated corneas were 5% and 8% thicker (835 versus 796 microns and 786 versus 728 microns, respectively) than the paired control corneas (P < 0.03). On days 10 and 14 after injury, both EGF-treated and control corneas were 19% and 12% thicker, respectively, than prewound the corneal thickness (621 microns). Seven days after injury, the corneas treated with EGF had an average of 76 +/- 28% more (P < 0.05) endothelial cell nuclei labeled with tritiated thymidine compared with that of the paired control eyes (2472 versus 1543 labeled nuclei). Fourteen days after injury, the central endothelial cell density of EGF-treated corneas was an average of 38 +/- 11% higher than that of the paired control eyes (P < 0.01, 1708 versus 1235 cells/mm2). The percentage of hexagonal cells in the wound area was an average of 14 +/- 4% higher (P < 0.01) than that of the paired control eyes (82% versus 69%), and the coefficient of variation of the cell size for EGF treated corneas was an average of 31% (P < 0.05) smaller than that of the paired control corneas (0.21 versus 0.29 [standard deviation]/mean cell size). CONCLUSIONS: A single intraocular application of EGF formulated in sodium hyaluronate after an endothelial cell injury significantly enhanced multiple parameters that are closely related to improved endothelial cell regeneration. PMID- 8505213 TI - The effect of hyaluronic acid on corneal epithelial cell proliferation. AB - PURPOSE: The authors investigated the mechanisms by which hyaluronic acid (HA) promotes corneal epithelial wound healing. The effect of HA on epithelial cell proliferation was examined in comparison with that of epidermal growth factor (EGF) and fibronectin (FN). METHODS: A penetrating linear incision (6-mm long) was made in the center of rabbit corneas. Immediately after wounding, the corneas were excised and cultured in TCM199 medium alone or medium containing HA (molecular weight, 860,000 Daltons; 100, 400, or 1000 micrograms/ml), EGF (25, 100, or 250 ng/ml), or FN (100 or 250 micrograms/ml) for 15 hr at 37 degrees C. The corneas were then labeled with tritiated thymidine (10 microCi/ml) and subjected to autoradiography. RESULTS: In the corneas cultured with HA at concentrations of 400 and 1000 micrograms/ml, the number of epithelial cells incorporating tritiated thymidine was significantly higher than that in the control corneas. In the corneas cultured with EGF at all concentrations, it was also higher than that of the control. FN did not affect cell proliferation. CONCLUSIONS: HA stimulates corneal epithelial cell proliferation. This stimulating effect of HA on epithelial cell proliferation might partly explain its effect in promoting corneal epithelial wound healing. PMID- 8505214 TI - Extraretinal signals for congenital nystagmus. AB - PURPOSE: Despite incessant to-and-fro oscillations of the eyes, persons with congenital nystagmus rarely report oscillopsia. This study evaluated the possibility that extraretinal signals of eye position are available to cancel the retinal image motion produced by nystagmus eye movements. METHODS: To assess the extraretinal signal for nystagmus, subjects pointed in the perceived direction of a target that was flashed for 2 msec in total darkness at various phases of the nystagmus waveform. RESULTS: All four subjects (two with jerk nystagmus and two with pendular nystagmus) made pointing errors that varied systematically according to what point in the nystagmus waveform the target was presented. In general, pointing errors varied in counterphase with changes in eye position, and amounted to approximately 25% of the nystagmus amplitude. CONCLUSION: These results indicate that extraretinal signals represent approximately 75% of the changes of eye position that occur in congenital nystagmus and therefore are potentially useful in preventing oscillopsia. PMID- 8505215 TI - Reading with rods: the superiority of central vision for rapid reading. AB - PURPOSE: To investigate why the central portion of the visual field is normally the optimal region for pattern recognition. METHOD: The study uses a reading paradigm in which the text can only be seen with rod vision. Reading rates were measured as the text was positioned in different parts of the visual field. RESULTS: Observers obtained the highest reading rates when rod-generated images were viewed at or near the fovea. CONCLUSION: The superiority of the central field for reading is neither linked to some exclusive property of the cone visual system, nor is it primarily related to visual sensitivity or spatiotemporal resolution. The superiority of reading in the central field is associated with some aspect of the visual cortical processes. PMID- 8505216 TI - Metallothionein shows an age-related decrease in human macular retinal pigment epithelium. AB - PURPOSE: To investigate the possible role of zinc-metallothionein in human retinal pigment epithelium with regard to age-related changes. METHODS: A cadmium/heme assay was used to quantitate metallothionein in isolated macular and peripheral retinal pigment epithelium from donors ranging in age from 28 to 91 yr (n = 16, mean age = 68.6 yr). RESULTS: It was found that peripheral retinal pigment epithelium contained significantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 +/- 2.2 micrograms metallothionein/mg cytosolic protein in donors younger than 70 yr, compared to 5.6 +/- 0.9 in macular retinal pigment epithelium from donors older than 70 yr, a 68% decline (P = 0.0007). In cultured retinal pigment epithelium, when we lowered the zinc concentration in the medium, metallothionein was reduced by 72% after 1 wk of incubation. CONCLUSIONS: It is suggested that lower levels of metallothionein in retinal pigment epithelium are caused by reduced metallothionein gene activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc. PMID- 8505217 TI - The effect of hypertonicity on aldose reductase, alpha B-crystallin, and organic osmolytes in the retinal pigment epithelium. AB - PURPOSE: Aldose reductase (AR), an enzyme implicated in diabetic complications of ocular tissues, has been suggested to play a physiologic role in kidney and, possibly, other tissues by elevating the organic osmolytes in conditions of heightened extracellular tonicity. Hypertonicity has been shown to induce AR and alpha B-crystallin in some cells. To examine if similar mechanisms are operating in the retinal pigment epithelium (RPE), another target tissue of diabetic complications, we studied the effect of hypertonic media on the induction of AR, alpha B-crystallin, myoinositol, taurine, and other free amino acids. METHODS: Human RPE cells were cultured in normal and hypertonic media containing 150 mmol/l NaCl or 200 mmol/l cellobiose in combination with 30 mmol/l galactose from 0-8 days. Western blot analysis with antibodies were used to measure the expression of AR and alpha B-crystallin. Hybridization of northern blots using AR and alpha B-crystallin complementary DNA probes were employed for the measurement of the respective messenger RNA for these proteins. Changes in the levels of myoinositol, galactitol, taurine, and other free amino acids were determined biochemically. RESULTS: AR and alpha B-crystallin messenger RNA levels rose 16 fold and 4-fold, respectively, when human RPE cells were cultured for 3 days in media supplemented with either 150 mmol/l NaCl or 200 mmol/l cellobiose. AR and alpha B-crystallin protein levels also increased significantly, as seen by western blots. Consistent with the increased AR, galactitol accumulated to a greater extent when human RPE cells were grown in media containing 30 mmol/l galactose plus 150 mmol/l NaCl compared with cells grown in 30 mmol/l galactose alone. An 11-fold increase in cellular myoinositol and a 1.4-fold increase in taurine was observed in cells exposed to hypertonic media. CONCLUSIONS: These findings suggest that human RPE cells are responsive to hypertonic stress by elevating AR activity and use intracellular organic solutes in an interactive manner to help regulate intracellular tonicity. PMID- 8505218 TI - The effects of myristyl gamma-picolinium chloride on the rabbit retina: morphologic observations. AB - PURPOSE: This study was designed to localize the site of action of myristyl gamma picolinium chloride (MGP) in the rabbit retina and to evaluate the extent of the structural damage induced by the drug. METHODS: The structural damage was assessed at the light microscopic level in eyes treated with various concentrations of MGP at different time intervals after intravitreal injection of the drug. Glial fibrillary acidic protein (GFAP) immunoreactivity was tested in the same eyes and served as an index of retinal damage. RESULTS: The rabbit retinas, examined about 1 mo after MGP injection, exhibited loss of photoreceptors and thinning of the retina in the regions close to the site of injection; remote retinal areas appeared morphologically intact or only slightly affected. Immunocytochemical analysis demonstrated the presence of GFAP in Muller (glial) cells throughout the entire retina. When the effects of MGP were examined at short time intervals (24 and 72 hr) after injection, severe morphologic damage in areas adjacent to the site of drug injection developed in parallel with the electroretinographic findings. However, GFAP could not be demonstrated. CONCLUSIONS: MGP, the preservative used in Depo-Medrol (Upjohn, Kalamazoo, MI), is highly toxic to the rabbit retina. PMID- 8505219 TI - Microvascular retinopathy in the Zucker diabetic fatty rat. AB - PURPOSE: To determine if quantifiable morphometric signs of retinopathy occur in the Zucker diabetic fatty rat (ZDF/Gmi-fa, formerly designated ZDF/Drt), a partially inbred strain in which the genetic propensity for diabetes is only expressed in obese males. METHODS: Retired diabetic (ZDF/Gmi-fa) and control lean Zucker (fa/+) breeder rats were examined for quantifiable evidence of microvascular changes of the retinal capillaries by gross examination, trypsin digestion of retinal vessels, and transmission electron microscopy. RESULTS: Gross examination of retinas and trypsin digestion of capillaries revealed no differences. Quantitative assessment of capillary cell nuclear density showed that diabetic retinas were hypercellular compared to lean rats (3.888 +/- 0.041 versus 3.304 +/- 0.046 nuclei per 100 microns (mean +/- SE), P = 0.0042). Transmission electron microscopic analysis of retinal capillary basement membrane thickness demonstrated thicker measurements in diabetic animals (mean thickness 21% greater in diabetic rats, P = 0.0307). CONCLUSIONS: This model may be useful for pharmacologic intervention studies because it is naturally and severely non insulin-dependent diabetic, there are quantifiable retinal vascular changes, and same-sex litter mates can be used as controls. PMID- 8505220 TI - Reduced accommodation in children with Down syndrome. AB - PURPOSE: To examine the accommodative accuracy and amplitude in children with Down syndrome. Accommodation is usually assumed to be good in children and is rarely measured. METHODS: A dynamic retinoscopy technique was developed that allows rapid and reliable measures of accuracy and amplitude of accommodation in infants and children. RESULTS: Use of the dynamic technique with a small sample of schoolchildren with Down syndrome shows that 80% have reduced amplitude of accommodation, in comparison to a control group of developmentally normal children. CONCLUSIONS: Optometric management of children with Down syndrome should include consideration of accommodation. PMID- 8505221 TI - Characterization of 222Rn entry into a basement structure surrounded by low permeability soil. AB - An experimental facility has been developed to monitor the entry rate and concentration of 222Rn in a basement-type structure surrounded by soil having a permeability on the order of 10(-11) m2. A data acquisition system recorded environmental conditions outside and inside the structures, plus basement air exchange rate information, every 15 min. Indoor 222Rn concentrations ranged from 400 to 1,400 Bq m-3. The observed 222Rn entry rate is highly variable and has two primary components; a constant input rate caused by diffusion of 222Rn through the concrete walls and floor, and a variable rate that depends upon indoor-soil pressure differentials of only a few pascals. Pressure differentials are dependent upon wind speed and wind direction. Stack effect was not significant. During a 2-wk period, with relatively calm winds, diffusion through the concrete walls and floor plus the floor-wall joint accounted for more than 80% of the total 222Rn entry. PMID- 8505222 TI - Function of radon emanation in dosimetric calculations. PMID- 8505223 TI - Who is a radiation worker? PMID- 8505224 TI - "On the Home Front" focus apparently misunderstood. PMID- 8505225 TI - Distributions of airborne radon concentrations in Seoul metropolitan subway stations. AB - Airborne 222Rn concentrations were surveyed to observe daily and seasonal variations in the 74 subway stations in the Seoul metropolitan area. Each station built of concrete elements usually has two or three stories underground with natural and mechanical ventilation facilities. The airborne radon level was determined three times: in July and August 1989, in January 1990, and in February 1991. Each study duration varied from 1-4 wk. The resulting distribution of annual average radon concentration in underground platforms was characterized by a geometric mean of 93 Bq m-3. Radon levels varied within a wide range from undetectable to 677 Bq m-3 in stations. In addition to the study of short- and long-term radon variation, various environmental factors having an influence on radon level were studied in order to obtain indications of the possible radon sources. PMID- 8505226 TI - Basic theory for the diffusive sampling of radon. AB - From the closed-form solution of the Fickian equation describing the uptake of radon by a diffusive sampler, the following are calculated: 1) the optimal estimate of the time-weighted average radon concentration; 2) the effect of the geometry of the diffusive sampler on performance; 3) the maximum sampling time consistent with a predetermined maximum error in the estimated time-weighted average concentration of radon; and 4) the effects of temperature and pressure on the performance of the sampler. It is shown that the maximum sampling error can be greatly reduced by dividing the adsorbent bed into two layers placed in series and by using a weighted average of the uptakes on the two layers. PMID- 8505227 TI - Environmental monitoring and dose assessment following the December 1991 K reactor aqueous tritium release. AB - Between 22 December and 25 December 1991, approximately 570 L of tritiated water was released from the K Reactor at the Savannah River Site. Analyses of river flow rates and measured tritium concentrations showed that approximately 210 TBq of tritium had been released from the reactor and was being transported down the Savannah River. Elevated tritium concentrations in the Savannah River were first detected on 26 December 1991. The maximum measured tritium concentration at Highway 301 (a major sampling point 37 km downstream of the Savannah River Site) was 2.5 Bq mL-1. A hypothetical maximum individual located at Highway 301 would have received a drinking water dose of approximately 0.35 microSv, less than 1% of the Environmental Protection Agency's 40 microSv y-1 drinking water standard. Concentrations at the intake canals to two water treatment facilities, approximately 160 km downstream, began to rise above normal on 28 December. The population dose to users of the downstream domestic water supplies and consumers of Savannah River biota was estimated to be 4.7 x 10(-3) person-Sv. PMID- 8505228 TI - A probabilistic estimation of atmospheric tritium dose. AB - A radiation dose distribution has been calculated for an individual exposed to tritium oxide (tritiated water vapor) in the atmosphere. A specific activity model was used that is similar to that detailed in the Nuclear Regulatory Commission's Regulatory Guide 1.109. The values of 19 parameters are sampled consistent with assigned probability distributions using a Latin Hypercube approach. Dose was estimated assuming a concentration of tritium in atmospheric moisture of 0.13 +/- 0.16 Bq mL-1. Conventional dosimetric methods for tritium that were consistent with the Regulatory Guide result in an estimate of 0.63 microSv for annual exposures to airborne tritiated water. For the same atmospheric tritium concentration, the estimated dose distribution is lognormal and ranges from 0.08-3.2 microSv (at 95% confidence) with a median value of 0.59 microSv and a 95th percentile of 2.6 microSv. PMID- 8505229 TI - Metabolism of injected plutonium in two healthy men. AB - The metabolism of plutonium has been studied following intravenous injection of 237Pu as Pu (IV) citrate into two healthy male volunteers. Measurements of the tracer in samples of blood and excreta were made by gamma-ray spectrometry, and patterns of organ uptake were investigated through serial measurements with a scintillation counter viewing the liver and selected skeletal sites. Excretion in urine and feces measured during the first 3 wk accorded closely with the patterns deduced by Durbin from the report of Langham et al. on patients injected with 239Pu. However, concentrations in blood were roughly twice those suggested by Durbin during most of the 14 d covered by our measurements. In one subject, the liver deposit increased to a plateau after about 21 d, at roughly 55% of the injection; in the other, the increase was prolonged, reaching about 70% after several months. PMID- 8505230 TI - Uncertainties in predicted radionuclide body burdens and doses from discrete stochastic source terms. AB - Expressions are derived in three cases for the expectation and uncertainty of body burdens and doses calculated from a linear model of environmental transport and human metabolism in terms of expectation and uncertainty in inputs of discrete, stochastic random variables. Three cases are compared to determine the relationship of the expectations and uncertainties under varying assumptions. In the constant input case, the input is selected randomly at the outset of the simulation period [O,T] from the distribution to which the population is exposed and then is held constant throughout [O,T]. In the two time-varying cases, random and autoregressive, it was assumed that N discrete stochastic exposures to the input were made uncorrelated and partially correlated, respectively. Each exposure was constant during each time interval of length T/N. The expectation values of the body burdens and doses in the constant input case were identical to those in the random case and the autoregressive cases for stationary inputs. The uncertainties of the body burdens and the doses in the constant input case were identical in the limit of rapid metabolism to those of the random case and the autoregressive cases for stationary inputs. In the limit of slow metabolism, the uncertainties of the body burdens and the doses in the constant input case were N1/2 and (3N/4)1/2, respectively, greater than those in the random case and were ((1 + alpha)/[(1 - alpha)N])1/2 and (4(1 + alpha)/[3(1 - alpha)N])1/2, respectively, greater than those in the autoregressive case for stationary inputs and autocorrelation coefficient alpha. That is, increasing the number of sampling periods decreases the uncertainty and increasing the autocorrelation increases the uncertainty. In an example application for ingestion of 137Cs at Bikini Island, a weak form of both slow and rapid metabolism limits apply and give the result that the uncertainty of the body burden in the constant input case is 18 times greater than the random case. For alpha = 0.5, the uncertainty of the body burden in the autoregressive case is 1.7 times greater than the random case. The smooth transition of the autoregressive case from the random case to the constant input case is shown as alpha increases from 0 (random) to 1 (constant). PMID- 8505231 TI - Factors that affect alpha particle detection in continuous air monitor applications. AB - An experimental study was conducted to characterize the full-width half-maximum values, peak shapes, and peak shifts of the energy spectra from alpha emitters in the forms of particulate matter on sampling filters and electro-deposited plated sources. Monodisperse 1.0-microns anhydrous uranium acetate aerosol particles were collected on seven types of sampling filters. Full-width half-maximum values at atmospheric pressure varied from 373 keV for a 3-microns pore size Fluoropore filter to 584 keV for a glass fiber filter. Monodisperse uranium acetate aerosols from 1.2-8.1 microns were collected on Millipore 1.2-microns pore size membrane filters to examine the self-absorption effect. Under vacuum, the corresponding full-width half-maximum values ranged from 241-1,011 keV. Successively heavier mass loadings of monodisperse 1.8-microns uranium acetate particles from 13.7-127 micrograms cm-2 caused the values to increase from 420 to 580 keV. With an electroplated 23.9-mm-diameter 239Pu source and a 25.4-mm detector, the distance between source and detector was incrementally increased from 3.2 to 6.4 mm--a range of distances that is typical of those found in alpha continuous air monitors. At atmospheric pressure, the values increased from 280 to 330 keV and the detector efficiency decreased from 30.5% to 20.9%. Tests with various sizes of sources and detectors suggest that a continuous air monitor should be designed so that the two are of approximately equal size. PMID- 8505232 TI - Simultaneous quantitative determination of 3H, 14C, 32P, 35S, 51Cr, and 125I on the surface of a paper disc using combustion. AB - A paper disc that retained 3H, 14C, 32P, 35S, 51Cr, and 125I on its surface was combusted in a flow-type combustion flask filled with oxygen. The combustion products containing five radionuclides, except 14CO2, were collected by washing the inner wall of the flask with 0.5-M hydrogen peroxide containing excess NaHSO3. The 14CO2 that remained in the gas phase of the flask was introduced into another flask for absorption into an organic base solution. By determining the radioactivity of both the solutions containing the respective radionuclides by means of NaI(Tl) and liquid scintillation counters, the six radionuclides in the solutions were quantified. The detection limit of surface contamination with this method was compared with the limit specified by Japanese law for the surface contamination of controlled areas. PMID- 8505233 TI - Indoor 222Rn concentrations in Istanbul houses. AB - Indoor average 222Rn concentrations have been measured in more than 400 houses in Istanbul city. The average radon concentrations in the houses were found to be between 10 Bq m-3 and 260 Bq m-3 and the mean value was 50 Bq m-3. PMID- 8505234 TI - Application of systematic error bounds to detection limits for practical counting. AB - Overly optimistic estimates of detection limits can result in the use of unrealistic conservatism for decisions about the presence of activity. In some practical counting situations, overly conservative detection limits can result in economically impractical actions. To help preclude such actions, systematic error bounds, uncertainties, and confidence levels can be used when determining critical levels (Lc), detection limits (Ld), and minimum detectable concentrations. This note discusses the selection of such error bounds and the development of detection limit parameters for practical applications. These parameters are shown to be successfully employed in sample activity and measurement process capability decisions for typical counting instruments. PMID- 8505235 TI - Assessment of the chemical form of gaseous 35S species produced during the production of H3(32)PO4. AB - The chemical form of gaseous 35S species produced during the production of H3(32)PO4 was characterized in order to reduce 35S discharge by understanding its production mechanism and chemical reactivity. An air sample was evacuated from the cell in which the H3(32)PO4 production was being carried out and collected in a sample gas reservoir. Gaseous sulfur species contained in the sample were condensed in a cold trap maintained at -180 degrees C and analyzed by means of gas chromatography using a flame photometric detector. Sulfur dioxide (SO2) was the only sulfur species detected. Equilibrium constant calculations showed that SO2 would be expected to be the predominant species produced by reactions of sulfur molecules (Sn:n = 2-8) with oxygen in air and that the quantity of SO2 produced would be reduced by heating the irradiated sulfur target under vacuum or in atmospheres of inert gases. PMID- 8505236 TI - Intercomparison of dosimetry measurements at the alternating gradient synchrotron from 1986-1988. AB - The responses of several types of high-energy personnel neutron dosimeters were studied in the operational radiation fields at the Alternating Gradient Synchrotron. Included in the study are intercomparisons of polycarbonate, type A neutron track emulsion, allyl diglycol carbonate, electrochemical etch allyl diglycol carbonate, TLD-600, and TLD-700. Some of the passive measurements were compared with active tissue-equivalent instruments. The trend for many but not all of the measurements was for type A neutron track emulsion to report the highest neutron dose equivalent. The polycarbonate returned intermediate values while allyl diglycol carbonate usually reported the smallest values. Quality assurance data from calibration sources through 1990 are also provided. PMID- 8505237 TI - Effects of different doses of zeranol on growth, hemoglobin, and carcass traits in veal calves. AB - Effects of different doses of zeranol on ADG, hemoglobin (Hb), feed efficiency (FE), and carcass traits were evaluated in special-fed veal calves in two trials. On d 0, calves were implanted subcutaneously in the middle third of the ear with either 0 (control, placebo pellet), 12, 24, 36, or 48 mg of zeranol. Trial 1 was conducted from February through May 1990 with 120 Holstein bull calves (17 to 21 d of age on d 0) and Trial 2 was conducted from May through August 1991 with 100 Holstein bull calves (24 to 28 d of age d 0). Calves were fed on an individual calf basis. Calves in Trial 1 that were implanted with 48 mg of zeranol had improved FE (P < .05) and ADG (P < .05) during Period 1 (0 to 43 d). No significant differences in ADG or FE were observed among treatments in Trial 2. Hemoglobin levels at slaughter averaged 7.88 +/- .096 and 8.19 +/- .149 g/dL over all treatments for Trials 1 and 2, respectively. The only postslaughter trait affected by zeranol dose was testicular weight. In both trials, testicular weight at slaughter decreased (P < .05) with increasing doses of zeranol. Dressing percentage tended to be higher for 48-mg implants than for controls but the difference was not significant. There were no significant zeranol dose effects on longissimus muscle area, flank color, carcass conformation, or percentage of fore vs hind-quarter weight. These results indicated that higher doses of zeranol improved ADG and FE during the first 6 wk after the trial period (to 8 wk of age), decreased testicular weight, and increased hide-on carcass dressing percentage for calves implanted with 48 mg of zeranol compared with those that received 0 mg of zeranol. PMID- 8505238 TI - Space requirements of barrows and gilts penned together from 54 to 113 kilograms. NCR-89 Committee on Confinement Management of Swine. AB - Two experiments, involving six experiment stations in the North Central Region of the United States, were conducted to examine the space requirements of mixed-sex pigs (barrows and gilts) from 54 to 113 kg live weight. In both experiments, corn or milo-soybean meal-based diets were formulated within stations to contain .6% lysine and no growth-promoting feed additive. In Exp. 1, entire pens of pigs given .56, .74, or .93 m2/pig remained on test until the week that the individual pen of pigs weighed > or = 113.6 kg. In Exp. 2, treatments were .56, .74, .93, and 1.11 m2/pig and individual pigs were removed during the week that they weighed > or = 113.6 kg. There was a linear (P < .005) improvement in ADG in Exp. 1 for the .56, .74, and .93 m2/pig treatments (.64, .69, and .72 kg/d). This response was accompanied by a linear (P < .05) improvement in gain:feed (.247, .258, and .261, respectively). In Exp. 2, the linear (P < .0005) response of ADG to increasing space allocation (.71, .76, .80, and .81 kg/d for the respective treatments) and the linear (P < .005) improvement in gain:feed (.265, .268, .274, and .281, respectively) suggested that pig performance reached a plateau. These results suggest that performance of pens of mixed-sex pigs grown to 113 kg live weight was maximized at the .93 m2/pig space allocation. PMID- 8505239 TI - Milk cholesterol concentration in sows selected for three generations for high or low serum cholesterol. AB - Female crossbred swine (Chester White x Landrace x Large White x Yorkshire) selected for three generations for low (L, n = 24) or high (H, n = 26) serum cholesterol at 8 wk of age were milked at d 20 or 21 of their first lactation to measure cholesterol, fat, lactose, protein, and ash concentrations. A contemporary, unselected control (C) group from the same original population (third lactation, n = 7) was sampled concurrently. All sows were fed a standard gestation, then lactation, diet that contained no cholesterol or added fat (all plant, corn-soybean meal). Genetic selection for low or high serum cholesterol at 8 wk of age induced corresponding changes in milk cholesterol and fat concentration in the third generation of selection, but not in any other milk constituents. Milk cholesterol concentrations (milligrams/100 grams fresh weight) were L, 25.3 +/- 3.0; C, 35.7 +/- 8.0; and H, 41.4 +/- 6.9 (L < C < H, P < .01). Corresponding values for milk fat were 5.7 +/- 1.3, 7.2 +/- .8, and 7.0 +/- .8 mg (L < C = H, P < .01). Serum cholesterol concentrations at 8 wk of age were L, 66.1 +/- 8.1; C, 93.7 +/- 13.7; and H, 126.2 +/- 9.7 mg/dL (P < .01). Milk cholesterol concentration was significantly correlated with serum cholesterol (r = .782, P < .01) and milk fat (r = .36, P < .01). It seems that selecting swine for low or high serum cholesterol at 8 wk of age induced changes in lipid metabolism reflected in differences in milk cholesterol concentrations. PMID- 8505240 TI - Effect of prepubertal body weight gain and breed on carcass composition at puberty in beef heifers. AB - Fourteen prepubertal Angus heifers, all of which reached puberty, and 11 Santa Gertrudis (SG) heifers, eight of which reached puberty, were divided into two treatment groups. There was no breed difference in age at puberty for those that reached puberty. Treatment 1 (T1) heifers, fed to gain .5 kg/d, tended (P < .11) to be older than Treatment 2 (T2) heifers, fed to gain 1 kg/d, at puberty. Body weight and height were greater (P < .01) in SG than in Angus heifers at puberty. Angus heifers in T2 deposited more fat over the rump during the 15 wk before puberty, whereas T1 SG heifers deposited the least amount of fat (P < .05). Heifers in T2 were heavier at puberty (P < .05), had faster growing longissimus muscle areas (P < .05), and deposited more fat over the rib (P < .01) as they approached puberty. The T2 (P < .05) and Angus (P < .05) rib sections had more dissectible subcutaneous fat than did T1 and SG rib sections. Angus heifers had higher marbling scores (P < .05), as well as higher total lipid percentages for seam fat (P < .05), longissimus muscle (P < .01), other lean tissue (P < .05), and subcutaneous fat (P < .01). Predicted total lipid content for the edible portion of the dressed carcass was higher for T2 heifers (P < .09). PMID- 8505241 TI - Relationship of body composition of mature ewes with condition score and body weight. AB - Fourteen mature, ovariectomized, western-range ewes with an initial mean BW of 72 +/- 4.5 kg and mean condition score (CS) of 7.5 +/- .3 were used to evaluate the relationship between CS and body composition. Diets of chopped straw and alfalfa hay were formulated to provide either maintenance energy or less than maintenance energy (100 or 60% of ME) to induce changes in BW and CS. After 180 d, ewes were weighted, scored for body condition, and slaughtered. All carcass components, viscera, and organs were analyzed for lipid, DM, and ash, and protein was determined by difference. Body weight and CS values were related by regression analysis to percentage of composition and weights of carcass components, carcass, and empty body. Body weight and CS were highly correlated (r = .89) and analysis indicated that each increase in CS resulted in an increase of 5.1 kg of BW. Condition score accounted for more variation of percentage of lipid in the empty body (R2 = .95) and carcass (R2 = .90) than did BW (R2 = .84 and .80, respectively). In contrast, BW accounted for more of the variation in carcass weight (R2 = .97) and empty BW (R2 = .99). Inclusion of both BW and CS in regression models did not increase the variation accounted for with the single best predictor. With mature western-range ewes in this study, CS was highly related to carcass lipids and could be used to describe energy reserves available to ewes. PMID- 8505242 TI - Milk production in Brahman and Angus cows on endophyte-infected fescue and common bermudagrass. AB - Daily milk yield and milk fat were estimated by method of milking machine in 60 Angus and 60 Brahman cows grazing common bermudagrass or endophyte-infected fescue during a 3-yr period. Averaged over monthly estimates, there was evidence (P < .05) of a dam breed x forage interaction in daily milk yield. Tall fescue decreased milk yield more in the Angus (1.64 kg/d, P < .01) than in the Brahman (.53 kg/d, P > .15). There were significant dam breed effects on both percentage of milk fat and daily milk fat yield; Brahman exceeded Angus by .68% (P < .01) and 34.3 g/d (P < .01), respectively. There were significant forage effects for both percentage of milk fat and daily milk fat yield; common bermudagrass exceeded tall fescue by .5% (P < .01) and 62.3 g/d (P < .01), respectively. These data indicate that incorporation of Brahman germplasm into a grazing system that uses endophyte-infected fescue may be beneficial in daily milk yield but will probably not prevent decreases in milk fat production associated with grazing endophyte-infected tall fescue. PMID- 8505243 TI - Factors influencing growth performance of beef bulls in a test station. AB - Performance records of 2,034 beef bulls tested at the Ellerslie Test Station, Alberta, Canada from 1974 to 1987 were analyzed to identify important factors that affect growth of bulls in a test station and to estimate the contribution of herd of origin to phenotypic variances of growth traits. Compared with herd of origin, age of dam, start of test age, and weight of bull were not of practical importance. Herd of origin accounted for a large fraction of phenotypic variance of weight, decreasing from 52 to 35% and from 37 to 30% from start to end of test in groups of small and large breeds, respectively. The effect of herd of origin on periodic and cumulative ADG decreased as the test advanced. The least affected periods were either 28 to 112 d or 56 to 112 d of test. However, the effect increased during the 112- to 140-d period. The effect of herd of origin on periodic relative growth rate was large and relatively stable up to 84 d, decreased during the 84- to 112-d period, and increased during the 112- to 140-d period. The effect of herd of origin on cumulative relative growth rate showed an increasing trend. Because ADG was highly influenced by herd of origin during the first 4 wk of test and least affected during the 28- to 112-d period or the 56- to 112-d period, a 56-d adjustment period followed by an 84-d test period for accurate evaluation of beef bulls for growth potential seems appropriate. PMID- 8505244 TI - Live animal measurement of carcass traits: estimation of genetic parameters for beef cattle. AB - Ultrasound measurements by trained and accredited sonographers on 9,232 Angus, Hereford, and Polled Hereford cattle at an average age of 450 d were used to estimate genetic and environmental (co)variances for weight at scanning (Wt), longissimus muscle area (LMA), longissimus muscle area adjusted to a constant weight of 400 kg (LMAawt), and fat depths at the rump and 12/13 rib sites. Estimated kilograms (ESMkg) and percentage of saleable meat yield (ESM%) were also calculated and analyzed. Subjective muscle scores, available for 2,488 animals, were also included in the analysis. Estimated heritabilities were 46% for Wt, 21% for LMA and LMAawt, 37% for rump fat, 30% for rib fat, 15% for muscle score, 44% for ESMkg, and 36% for ESM%. The two measurements, LMA and LMAawt, had high genetic (.82) and environmental (.91) correlations. The two fat depths were also highly correlated (.86 genetic; .67 environmental). Weight at scanning was moderately correlated with LMA (.45 genetic; .41 environmental). Differences between breeds could not be detected, but some variation in parameter estimates between data sets of the same breed was observed. Environmental correlations between fat depths or muscle score and Wt were approximately .3; genetic correlations were .07 to .12. Subjective muscle score had marginally higher genetic correlations with LMA than with LMAawt (.22 vs .08) but similar environmental correlations (.31 vs .27). Results show that carcass traits measured by ultrasound and predictions of meat yield have genetic variability, are moderately heritable, and that genetic progress based on genetic evaluation by mixed-model analysis can be made. PMID- 8505245 TI - The contribution of progeny of uncertain paternity to the accuracy of sire evaluation. AB - Recent advances in statistical methodology now permit the genetic evaluation of animals with uncertain pedigrees. Although widescale practice of these techniques is not likely, implementation will never occur until we characterize the effect of uncertain pedigrees on the accuracy of animal evaluation. This work develops the framework for such a characterization, illustrating the contribution of uncertainly identified records to accuracy of evaluation through a hypothetical example. The effect of including records of uncertain paternity is greatest for sires with few certainly identified progeny. Thus, young sires stand to benefit the most from the inclusion of progeny records with uncertain paternity. In general, as the level of uncertainty in the data is replaced by the inclusion of progeny with certain paternity, the accuracy of evaluation increases. However, situations do arise in which the accuracy unexpectedly declines with the addition of progeny records with certain paternity. PMID- 8505246 TI - Longevity and lifetime productivity of cows in a purebred Hereford and two multibreed synthetic groups under range conditions. AB - Records on 983 cows born during a period of 10 yr (1966 to 1975) were used to estimate longevity and lifetime productivity of cows raised under range conditions. The cows were from a purebred Hereford and two multibreed synthetic groups, one composed of beef breeds (Beef Synthetic #1) and the other composed of two-thirds dairy breeds and one-third beef breeds (Dairy Synthetic). The cows were raised under a stringent culling system in which all heifers were exposed to bulls as yearlings and were expected to wean a calf each year thereafter or they were culled. Cows were also culled for other reasons, such as severe calving problems, bad udders, and leg and feet problems. The mean longevity was 4.2 yr; cows from the synthetic breed groups produced longer (P < .01) than Hereford cows, due to a relatively faster rate of removal at all ages in the purebred Hereford group. The mean values per cow for lifetime productivity traits were 2.7 and 2.5 for number of calves born and weaned and 101.9 kg and 482.9 kg for weight of calf born and weaned, respectively. Male calves were not castrated, and weights of female calves were adjusted to a male basis. Over their lifetimes, Dairy Synthetic cows were more productive, in terms of number and weight of calves born and weaned, than Beef Synthetic #1 cows, which in turn were more productive than purebred Hereford cows (P < .01). PMID- 8505247 TI - Genetic parameter estimates and expected progeny differences for mature size in Angus cattle. AB - Mature size records collected on Angus cows of 5 to 12 yr of age were used to estimate heritabilities, genetic correlations, and EPD for mature weight and mature height. A total of 256 sires were evaluated using mature size data collected on 2,732 daughters. Data were analyzed using REML procedures with a two trait sire model to estimate sire and error variances for mature weight and height. Models with and without adjustment of weight for body condition score were investigated. The linear model for weight and height included fixed herd year-month the records were taken, sire genetic group, random sire, and residual error. Using unadjusted mature weights, heritabilities were .48 +/- .10 for weight and .83 +/- .11 for height. When condition score adjustments were made, heritability estimates were .45 +/- .10 for weight and .83 +/- .11 for height. Genetic (phenotypic) correlations between weight and height were .78(.58) for adjusted data and .66(.54) with no adjustment. Spearman rank correlations between sire EPD for adjusted and unadjusted data were .94 for weight and .99 for height. Two-trait models of mature cow weight with immature weights (birth weight, 205-d weight, 365-d weight) were used to assess genetic relations among mature and immature cow weights. Genetic correlations between mature weight and immature weights were .57 with birth weight, .62 with 205-d weight, and .45 with 365-d weight. PMID- 8505248 TI - Culture conditions for the production of porcine myotubes and myoballs. AB - The existence of a method for culturing porcine muscle cells would greatly facilitate the development of new breeding criteria for stress resistance and growth regulation in pig breeding. Also, many effects of nutritional or pharmacological components that influence animal performance could be studied first in muscle cell preparations. Therefore, we developed a specific procedure to culture porcine skeletal muscle cells from well-established methods for murine and human muscle cell culturing. Best results were obtained by isolating satellite cells from muscle tissue removed postmortem after normal slaughter procedure, using enzymatic dissociation. The satellite cells were allowed to proliferate for 3 to 5 d in a culture medium composed of 83% Ham's F-12 medium, 15% fetal calf serum (FCS), and 2% chick embryo extract (CEE). Well before reaching confluence, the cells were transferred to collagen-coated dishes filled with Dulbecco's modified Eagle's medium containing 5% horse serum (HS) for the differentiation to multinucleated myotubes. Also, .5% FCS can be used instead of HS. Besides the fusion to myotubes, the presence of voltage-sensitive Na+ channels is regarded as a specific feature of the muscle phenotype of the cells. To perform electrophysiological experiments of good quality, myotubes were converted into freely floating "myoballs." Voltage-clamp experiments in the whole cell mode showed transient inward currents that had kinetics and voltage dependences very similar to those of the Na+ currents in human myoballs. The porcine Na+ currents were almost completely blocked by 1 mumol/L of tetrodotoxin, indicative of the presence of the adult form of the Na+ channel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505249 TI - Effects on meat quality of the use of clenbuterol in veal calves. AB - The objective of this study was to examine the effects of clenbuterol administration on meat quality traits of veal. Sixteen Holstein-Friesian veal calves (male) were randomly assigned to one of four treatment groups; either control (n = 4) or clenbuterol-treated (1.6 micrograms.kg [corrected] BW-1.d-1, 42 d) with a withdrawal period between clenbuterol treatment and slaughter of 8 d (n = 4), 4 d (n = 4), or 2 d (n = 4). All animals were slaughtered at the same day at a commercial slaughterplant. At 30 min postmortem the carcasses were split and the right carcass side was electrically stimulated. After 24 h of cooling the longissimus, semimembranosus, triceps brachii, and psoas major muscles were excised and vacuum-packaged. After 1, 7, and 13 d of vacuum storage at 2 +/- 2 degrees C the muscles were sampled to determine tenderness, water-holding capacity, and color characteristics. Clenbuterol treatment resulted in a slower rate of pH decline in the unstimulated longissimus muscle but did not affect the ultimate pH. Clenbuterol treatment resulted in toughening of the longissimus, semimembranosus, and triceps brachii muscles after 1 and(or) 7 d of storage (P < .05). It is suggested that this resulted from a decrease in postmortem proteolysis because both the intensity of a 30-kDa peptide and the myofibril fragmentation index were lower in clenbuterol-treated muscles. Clenbuterol treatment resulted in increased lightness (L*-value) of longissimus and semimembranosus muscles (P < .05), coincident with a lower water-holding capacity. In a following experiment, the effect of clenbuterol administration (0 [n = 5] and 1.0 [n = 5] mg/kg of feed for 27 d) on calpain and calpastatin levels at 1 d postmortem in longissimus muscles of Friesian Pie Noire veal calves was investigated. Clenbuterol administration resulted in an increase in calpastatin levels (P < .05) and a trend (P < 0.1) toward a decrease in mu-calpain activity at 1 d postmortem. PMID- 8505250 TI - Effects of high-forage diets with added palm oil on performance, plasma lipids, and carcass characteristics of ram and ewe lambs. AB - The objectives of this study were to determine the effects of high-forage diets with and without added dietary palm oil (high in palmitic acid) fed at equalized ME intakes on performance, plasma lipids, and carcass characteristics of growing ram and ewe lambs. Thirty-one Hampshire or Suffolk lambs (35.7 kg BW) were used in a 2 x 2 factorial arrangement of the following treatments: 1) rams, no palm oil (R-NPO); 2) ewes, no palm oil (E-NPO); 3) rams, 10.7% dietary palm oil (R PO); and 4) ewes, 10.7% dietary palm oil (E-PO). Both diets consisted of 77% forage and 23% concentrate. Diet DM contained 15.0% CP and 2.14 Mcal of ME/kg (NPO) or 2.62 Mcal of ME/kg (PO). Lambs were fed individually specified amounts of diet based on BW to equalize ME intake (.20 Mcal of ME/kg of BW.75) for both dietary treatments. Lambs were weighed and feed intakes were adjusted weekly. Lambs were bled by jugular venipuncture on d 28, 56, and 84 and were slaughtered after they had been fed the diets for 90 d. Lambs fed PO had greater (P < .01) ADG and efficiency (ADG/ME intake) than lambs fed NPO. Plasma concentrations of cholesterol, high-density lipoprotein cholesterol, triglycerides, and nonesterified fatty acids were increased (P < .01) by feeding PO. Lambs fed PO were fatter than lambs fed NPO, as evidenced by greater subcutaneous fat thickness and kidney and pelvic fat. Ewes had greater (P < .01) subcutaneous fat than did rams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505251 TI - Effect of initial breeding weight and management system using a high-producing sow genotype on resulting reproductive performance over three parities. AB - A study was conducted with sows of a high-producing genotype to evaluate their reproductive performance using three breeding weights over a three-parity period in two management systems. A total of 114 F1 gilts (Landrace x Yorkshire) were used in a split-plot, randomized, complete block experiment conducted as a 3 x 2 factorial arrangement of treatments in two replicates. Three gilt breeding weights of 120, 135, and 150 kg were achieved by feeding 1.8, 2.3, or 3.2 kg/d of a .73% lysine corn-soybean meal (C-SBM) diet, respectively, from 5 to 8 mo of age. Two locations, each with different management systems, were considered the main plot and consisted of 1) outside, concrete-floored gestation lots and indoor farrowing pens or 2) indoor gestation pens and farrowing crates. All sows were fed 1.8 (Parity 1) or 2.1 (Parity 2 and 3) kg/d of a .73% lysine C-SBM diet during the breeding and gestation periods, whereas a .82% lysine C-SBM diet with 5% added fat was available ad libitum during lactation. All sows lost weight during the first lactation; larger weight losses occurred as breeding weight increased (P < .01). During the second and third lactations the 135- and 150-kg sow breeding groups had less lactation weight change, whereas the 120-kg group lost more weight, resulting in a breeding weight x parity interaction (P < .01). The 120-kg breeding weight group consumed less feed (P < .05) for the three lactation periods than did the heavier weight groups. Initial breeding weight had no effect on number of pigs born (total, live) or pig and litter weights at birth. Pig mortality increased with increasing breeding weight (P < .01) and parity (P < .05), a response that was exacerbated when sows farrowed in pens vs crates. Postweaning breeding intervals and sow removal from the experiment were not significantly affected by initial breeding weight, but a numerically higher percentage of sows in the 120-kg group were anestrous or failed to conceive than the percentage of such sows in the heavier weight groups. These data suggest that an initial breeding weight of approximately 135 kg at 8 mo of age may be best when sows farrow in crates, whereas when sows farrow in pens a lower breeding weight may be more desirable. PMID- 8505252 TI - Lecithin in swine diets: I. Weanling pigs. AB - One digestibility experiment (Exp. 1) and two growth experiments (Exp. 2 and 3) were conducted to evaluate the use of lecithin as an emulsifier of soy oil and(or) an energy source in a two-phase starter diet program. Phase 1 consisted of d 0 to 14 postweaning, and Phase 2 consisted of d 14 to 35 postweaning. Diets were based on corn, soybean meal, and 20% dried whey and contained a constant ME:lysine level. In Exp. 1 and 2, two levels of lecithin (0 and 2%) at two levels of soy oil (0 and 6%) were investigated. In both experiments, there was no interaction between lecithin and soy oil for any traits measured. In Exp. 1, the apparent digestibility of fat increased significantly with increased fat level in the diets. Addition of lecithin to diets improved (P < .05) nitrogen retention, and the addition of soy oil significantly improved apparent digestibility of DM, GE, fat, and CP. In Exp. 2, there was no significant effect of lecithin or soy oil on ADG. In Phase 2 and overall, the inclusion of lecithin and soy oil to diets significantly increased gain/feed but did not significantly improve gain/ME intake. In Exp. 3, pigs were fed diets containing 0, 1, 2, or 3% lecithin. The addition of lecithin to diets did not affect ADG, ADFI, gain/feed, or gain/ME intake during Phases 1, 2, or overall. These results fail to demonstrate that the addition of lecithin to diets for young pigs improves utilization of soy oil or growth performance. PMID- 8505253 TI - Lecithin in swine diets: II. Growing-finishing pigs. AB - Lecithin was investigated in diets for growing-finishing pigs. Diets were based on corn and soybean meal and contained a constant ME:lysine level. The use of lecithin as an emulsifier on utilization of soy oil by the pig was investigated in Exp. 1. Diets were arranged in a 2 x 2 factorial structure with two levels of lecithin (0 and 2%) and two levels of soy oil (0 and 6%). There were no interactions between lecithin and soy oil for any measurements of growth performance. In general, the inclusion of lecithin or soy oil did not affect (P > .1) ADG but did improve (P < .01) gain/feed during the finishing period and during the entire experiment. During the finishing period, gain/ME intake was improved (P < .01) by both lecithin and soy oil. The use of lecithin as an energy source for pigs was investigated in Exp. 2. Dietary treatments were corn and soybean meal diets with 0, 1, 2, or 3% lecithin. There were no significant differences in performance of pigs as measured by ADG, ADFI, gain/feed, and gain/ME intake among the four lecithin levels. Lecithin did not improve utilization of soy oil by growing-finishing pigs. Furthermore, lecithin was not an efficacious source of supplemental dietary fat for growing-finishing pigs in this study. PMID- 8505254 TI - Enhancement of sow reproductive performance by beta-carotene or vitamin A. AB - Two experiments were conducted at separate commercial farms. In Exp. 1, all primiparous sows and an equal number of multiparous sows weaned each week were randomly assigned to one of four treatment groups. Treatments consisted of one i.m. injection on the day of weaning of 0, 50, 100, or 200 mg of beta-carotene. Sows were checked for estrus with boars once daily and mated at first estrus after weaning. A sample of sows (n = 100) was selected for determination of plasma beta-carotene and vitamin A. Blood samples were obtained from another group (n = 120) 14 d after injection to determine plasma progesterone. In Exp. 2, treatments consisted of i.m. injection of 200 mg of beta-carotene, 50,000 IU of vitamin A, or vehicle on the day of weaning, on the day of mating, and on d 7 after mating. In both experiments, the sow diet was supplemented with 11,000 IU/kg of vitamin A. In Exp. 1, there was no effect of dose of beta-carotene on the interval from weaning to estrus or on the repeat service rate. There was a dose x parity interaction on the number of pigs born dead (P < .01) and born alive (P < .10), because treatment with beta-carotene did not affect reproduction in primiparous sows, but litters subsequently farrowed by multiparous sows had more pigs born alive and fewer pigs born dead. There was a dose x day interaction (P < .05) on plasma beta-carotene; beta-carotene was elevated on d 6 and 13 after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505255 TI - Effect of selecting for increased lean tissue growth rate in swine on low or high dietary protein levels. AB - To determine the optimum nutritional status when selecting for increased daily lean tissue growth rate (LTGR) two selection lines of Swedish Yorkshire pigs were tested for responses and interactions when fed three diets that contained .70, .85, or 1.00% lysine and 13.9, 15.8, or 17.5% CP, respectively. Selection for increased LTGR was made while the pigs were fed diets with low CP (13.1%) and lysine (.64%) (LP line) or high CP (18.5%) and lysine (.96%) (HP line) concentrations. Two experiments were performed after three generations of selection, with pigs fed from 25 to 105 kg BW. The animals were fed restrictedly on an energy basis in relation to BW. A total of 236 pigs were tested. When testing main effects of selection line, the HP line had superior average daily lean tissue gain (P = .031), carcass lean percentage (P = .007), and lean to feed ratio (P = .028) compared with the LP line. No diet x genotype interaction was found for any of the traits tested. The selection in the HP line resulted in faster genetic progress because this line had best overall performance. This supports the theory that the most efficient selection is achieved in an environment that enables the animals to express their genetic capacity for the desired trait. PMID- 8505256 TI - Pharmacokinetics of a recombinant bovine growth hormone and pituitary bovine growth hormone in lactating dairy cows. AB - The disposition of pituitary-derived bovine growth hormone (pbST) and of a recombinant bovine growth hormone (rbST) produced by Lilly (somidobove, USAN) were compared after an intravenous bolus administration (36.69 micrograms/kg for pbST and 35 micrograms/kg for rbST) to eight lactating cows in a crossover study. It was shown that dose-dependent parameters (volume of distribution, clearance) were significantly different between the two test articles. The steady mean state volume of distribution (.10 +/- .018 vs .12 +/- .015 L/kg) and clearance (.119 +/ .012 vs .143 +/- .011 L.kg-1.h-1) were lower for the pbST than for the somidobove. In contrast, the mean (+/- SD) residence times were not different for the two test articles (50.0 +/- 8.6 vs 46.9 +/- 5.9 min for pbST and somidobove, respectively). The origin of the difference is unclear, but it cannot be explained by the slight difference between the administered dose of the two test articles (< 5%) because the actual dose rate was used to calculate all dose dependent parameters. PMID- 8505257 TI - Effects of insulin, insulin-like growth factor I, and gonadotropins on bovine granulosa cell proliferation, progesterone production, estradiol production, and(or) insulin-like growth factor I production in vitro. AB - The objectives of the present studies were to determine the effect of insulin, insulin-like growth factor I (IGF-I), testosterone, and FSH on proliferation, progesterone production, and(or) estradiol production of bovine granulosa cells. In addition, existence of IGF-I mRNA in granulosa cells and in vitro IGF-I production by granulosa cells were assessed. Cells from small (1 to 5 mm) and large (> or = 8 mm) follicles were collected from cattle and cultured for either 3 or 4 d. When cells from small follicles were cultured, insulin (.1 to 10 micrograms/mL) and IGF-I (100 to 400 ng/mL) increased (P < .05) cell numbers compared with controls. Insulin alone or IGF-I alone increased (P < .05) progesterone production per cell by severalfold on d 4. In cells from both sizes of follicles, insulin (1 microgram/mL), in the presence of FSH, increased estradiol production per cell. In contrast, IGF-I (100 ng/mL) inhibited estradiol production by cells from small follicles and stimulated estradiol production by cells from large follicles. Insulin-like growth factor II (100 ng/mL) and insulin at higher doses (> or = 5 micrograms/mL) had no effect on estradiol production by cells from small and large follicles. Granulosa cells contained four IGF-I mRNA transcripts and produced IGF-I in vitro. These results support the hypothesis that insulin and IGF-I may have direct local effects on bovine ovarian function, and that these effects are influenced by dose and size of follicle. PMID- 8505258 TI - Effects of grazing allowance and system on the use of corn-crop residues by gestating beef cows. AB - Duplicate fields of corn-crop residues were grazed by 3- to 11-yr-old Charolais x Angus and Charolais x Angus x Simmental cows (average BW = 630 kg) in midgestation at allowances of .41, .82, and 1.64 ha/cow in a continuous-stocking system for 56 d in 1988 (yr 1) and 1989 (yr 2) and for 51 d in 1990 (yr 3), or at .41 ha/cow in a strip-stocking system for 56 and 51 d in yr 2 and 3, respectively. Body weight gains by cows grazing continuously stocked fields at .41, .82, and 1.64 ha/cow were -.06, -.01, and .41 kg/d (P = .02), respectively. Body weight changes by cows grazing continuously stocked and strip-stocked fields at .41 ha/cow were .15 and .30 kg/d in yr 2 and -.33 and -.53 kg/d in yr 3 (system x year, P = .08), respectively. Percentages of in vitro OM disappearance (IVOMD) of crop residues selected by ruminally fistulated steers (P = .22) and cow crop residue DMI (% of BW; P = .03) were 52.5, 1.64; 60.1, 2.87; and 61.7, 2.97 in fields continuously stocked at .41, .82, and 1.64 ha/cow after 21 to 35 d of grazing in yr 2 and 3, respectively. Selected crop residue IVOMD (P = .04) and crop residue DMI (percentage of BW, P = .07) were 58.0 and 2.46, respectively, in fields strip-stocked at .41 ha/cow. Mean yields of OM (P < .01) and IVOMD (P < .01) were 4,605, 2,136; 5,347, 2,495; and 5,761, 2,688 kg/ha in fields continuously stocked at .41, .82, and 1.64 ha/cow, respectively. Results imply that cows grazing corn-crop residues in continuously stocked fields are less likely to gain BW at grazing allowances < 1.64 ha/cow for 56 d. Differences in BW gains between cows grazing strip-stocked and continuously stocked crop residue fields were weather-dependent. PMID- 8505259 TI - Technical note: ruminal vein catheterization and continuous blood flow measurement in ruminal arteries of sheep. AB - Eight wethers were used to test the technique. Silicone rubber catheters were introduced into both ruminal veins so that their tips lay a few centimeters from the splenic vein. Arterial blood flow to the rumen was measured by an ultrasonic transit-time flow meter with 3-mm probes implanted around the left and right ruminal arteries. No loss of patency of the venous catheters was observed before slaughter (2 to 6 mo after surgery). There was no evidence of extensive vascular trauma due to catheterization at postmortem examination. In vivo calibration of the flow probes showed that reliable measurements could be made until at least 6 mo after implantation. With an accurate method of blood flow measurement in ruminal arteries and guaranteed long-term catheter patency, it would be possible to make reliable estimates of nutrient uptake across the ruminal wall of sheep over an experimental period of several months. PMID- 8505260 TI - Ruminal distribution of zinc in steers fed a polysaccharide-zinc complex or zinc oxide. AB - Six Holstein steers (initial BW 335 kg) were used in a replicated 3 x 3 Latin square design to study the distribution of Zn in ruminal contents from a conventional Zn source (ZnO) or Zn sequestered to a polysaccharide (PC-Zn). Treatments consisted of a basal diet (no Zn supplementation) and the basal diet supplemented with Zn from either PC-Zn or ZnO. Steers were provided with 208, 920, or 896 mg of Zn/d from basal, PC-Zn, or ZnO, respectively. On collection day, steers were dosed with 800 mg of Zn from each Zn supplement and whole ruminal contents (WRC) were sampled at 1, 2, 4, 6, and 8 h postdosing. The cell free (soluble) Zn concentrations in steers fed the PC-Zn or ZnO supplements decreased (P < .05) rapidly after dosing. Mean Zn concentrations of the cell-free fraction were considerably lower than either microbial or particle fractions of WRC. Compared with ZnO, the PC-Zn source resulted in higher (P < .05) cell-free Zn at 1 and 2 h after dosing and higher (P < .05) Zn concentrations (micrograms/gram of DM) in the fluid- and particle-associated microbial and particle fractions. Compared with basal, fluid-associated microbial DM concentration tended to be higher (P < .10) at 6 and 8 h with PC-Zn and ZnO. Results indicate a rapid disappearance of Zn from the soluble fraction and a high concentration of Zn in the DM of the microbial and particle fractions of WRC. Furthermore, PC-Zn resulted in higher levels of Zn in all fractions of WRC, and Zn supplementation tended to increase microbial DM production at later sampling times. PMID- 8505261 TI - A net carbohydrate and protein system for evaluating cattle diets: IV. Predicting amino acid adequacy. AB - The Cornell Net Carbohydrate and Protein System was modified to include an amino acid submodel for predicting the adequacy of absorbed essential amino acids in cattle diets. Equations for predicting the supply of and requirements for absorbed essential amino acids are described and presented. The model was evaluated for its ability to predict observed duodenal flows of nitrogen, nonammonia nitrogen, bacterial nitrogen, dietary nonammonia nitrogen, and individual essential amino acids. Model-predicted nitrogen, nonammonia nitrogen, bacterial nitrogen, and dietary nonammonia nitrogen explained 93.2, 94.6, 76.4, and 79.3% of the observed duodenal flows, respectively, based on R2 values from predicted vs observed regression analysis. Based on slopes of regression lines, model-predicted duodenal nitrogen and nonammonia nitrogen were different from observed duodenal flows (P < .05), whereas model-predicted bacterial nitrogen and dietary nonammonia nitrogen were not different from observed duodenal flows (P < .05). Model-predicted duodenal flows of individual essential amino acids explained 81 to 90% of variation in observed duodenal amino acid flows. Based on slopes of regression lines, model-predicted duodenal threonine, leucine, and arginine were the only amino acids different from observed duodenal flows (P < .05). Ideas for further model improvements and research in amino acid metabolism were also presented. PMID- 8505262 TI - Predicting amino acid adequacy of diets fed to Holstein steers. AB - The Cornell Net Carbohydrate and Protein System (CNCPS) and NRC (1985) models were evaluated for accuracy in predicting metabolizable protein (MP) and essential amino acid (EAA) allowable ADG, using chemical body and feed composition data from feeding trials with Holstein steers. Nine Holstein steers (113 to 200 kg) were slaughtered and determined to have the following whole-body essential amino acid composition of (grams/100 grams of protein): arginine, 5.94; histidine, 2.07; isoleucine, 2.28; leucine, 5.72; lysine, 5.81; methionine, 1.99; phenylalanine, 3.04; threonine, 3.52; tryptophan, .57; and valine, 3.32. The NRC and CNCPS were then tested against data from 25 feeding periods, each representing the 56-d growth of 10 Holstein steers (mean BW of 162 kg), to determine their ability to predict the gain allowed by the supply of MP and the first-limiting EAA. The NRC (1985) system accounted for 46% of the variation in MP allowable gain, with an average bias of -30%. The CNCPS accounted for 87 and 73% of the variation in MP and EAA allowable gain, with a bias of 8 and 5%, respectively. The bias was reduced to 3% (R2 of .82) when ADG was predicted by the factor (ME, MP, or EAA) first-limiting ADG. PMID- 8505263 TI - Evaluation of housing systems for sows. AB - Housing systems of sows have to meet the requirements of the sow and the requirements of the producer. Criteria that have to be taken into account are productivity, labor input and management, welfare and health, and economy. Different housing systems for sows are described with respect to these criteria. PMID- 8505264 TI - Review: molecular biology of transgenic animals. AB - The amazing pace of discovery within the field of molecular biology has expanded the understanding of as well as the potential for genetic engineering in laboratory and domestic animals. Recently, specific techniques have been perfected, including recombinant DNA, genetic cloning, analysis of gene expression, and the sequencing of nucleic acids and proteins. These molecular techniques combined with methods allowing transfer of the recombinant genes into living cells and fertilized eggs advent the production of transgenic mice and other animals, the application of which is unlimited. PMID- 8505265 TI - Status of research with transgenic farm animals. AB - Microinjection is the predominant method used to transfer genes into farm animals. Current research is devoted to improvement of productivity traits, enhancement of animal health, and production of biomedically useful human health products. Initial transgenic research primarily involved genes coding for growth hormone (GH), growth hormone-releasing factor (GRF), and insulin-like growth factor I (IGF-I). More recent investigations have attempted to stimulate muscle development, to use bacterial enzymes so animals can synthesize certain essential amino acids, to induce expression of specific immunoglobulin or disease resistance genes, and to direct expression of human proteins to the mammary gland, specific organs, or specific cells for production of useful human health products. The main limitations to progress are the lack of useful cloned genes for productivity traits and disease resistance and the insufficient knowledge of mechanisms involved in regulation of transgenes. PMID- 8505266 TI - Challenges and opportunities for integrating genetically modified animals into traditional animal breeding plans. AB - Techniques have been developed to introduce specific genes from one species into the germplasm of another, including livestock. This paper reviews reports on evaluation, selection, and breeding procedures for introduction and multiplication of transgenes in breeding populations of livestock. Before transgenes are introduced and multiplied in commercial breeding populations, it is necessary to test transgenics extensively for both favorable and unfavorable transgene effects. Parent stock used to produce transgenic founder animals should be selected to excel in polygenic breeding value for economically important traits, especially if founder animals or their sons are to be used directly by AI in commercial populations. However, polygenic breeding value of founder transgenic animals and inbreeding depression are of negligible importance if a transgene is introgressed into a selection nucleus population from three or four generations of backcrossing. Transgenic development should be economically viable for traits with major effects on net merit, especially in the dairy industry, where transgenic sires can be used extensively by AI. A minimum effect of about 10% of the mean (or one phenotypic standard deviation) is a reasonable approximation of the minimum transgene effect that would be necessary to justify introgression into a nucleus swine population. A transgene effect of 10 to 20% of the mean would be required for most economic traits in beef cattle. PMID- 8505267 TI - Resource requirements for transgenic livestock research. AB - Transgenic research usually involves a large investment in carrying out a series of low-efficiency steps to produce a few transgenic founder animals, and then characterizing a transgenic line of animals derived from each founder. There is considerable variation in phenotype among transgenic lines made with the same DNA construct. In the case of livestock species, to produce one founder animal that expresses a transgene typically requires injection of DNA into hundreds of embryos, which then are transferred to reproductive tracts of recipients for gestation to term. To reduce costs, embryos sometimes are screened by analysis of a biopsy using the polymerase chain reaction, and only those with the transgene are transferred. Characterizing a transgenic line often is a greater logistical undertaking than making the transgenic founder. Ideally, animals should be evaluated for the transgenic trait as well as for absence of undesirable side effects in both sexes in both the hemizygous and homozygous transgenic states. Producing homozygous transgenic animals requires mating relatives, resulting in inbreeding. Characterization of transgenic lines takes many years in species with long generation intervals; the whole process is much less costly in litter bearing species. Because of safety and efficacy issues, characterizing transgenic lines for agricultural production purposes will be more demanding than characterizing them for research purposes. At a minimum, three broad areas of expertise are required for successful transgenic projects: molecular biology, embryo micromanipulation/reproductive physiology, and knowledge of the biology of the tissues/systems affected by the transgene. Facilities, including surgical suites for most projects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505268 TI - Patents for genetically modified animals. AB - Should genetically engineered animals be patented? This issue has been one of the most contentious as lawmakers have grappled with how best to protect intellectual property. Since the 1980 case of Diamond v. Chakrabarty, in which the U.S. Supreme Court ruled that a living microorganism is patentable, the U.S. Patent and Trademark Office has determined that plants and nonhuman animals can be patented. These policy decisions have led to congressional debate on whether animals should be patentable subject matter. Patenting of living organisms is unique for three reasons: the invention itself is alive; the invention in some instances can reproduce itself; and the invention sometimes cannot be adequately described for patent specification purposes, leading to the need for deposit of the invention for patent purposes. PMID- 8505269 TI - Food safety and inspection service update on food safety of animals derived from biotechnology experiments. AB - Recent progress in the field of biotechnology and the production of transgenic livestock has raised a question regarding the need for the regulation of these animals. There is also the need to regulate nontransgenic animals resulting from transgenic animal research. It is anticipated that several governmental agencies will be involved in regulatory issues pertaining to these animals. The United States Department of Agriculture (USDA), Food Safety and Inspection Service (FSIS) will ultimately be responsible for ensuring that transgenic animals intended for human consumption are wholesome, unadulterated, and properly labeled. The FSIS has implemented a program for the regulation of slaughtering nontransgenic animals resulting from transgenic animal experiments. However, the FSIS has not yet approved any transgenic livestock for slaughter. Scientists from the FSIS, in conjunction with other government agencies, are currently developing guidelines for the slaughter of transgenic animals. PMID- 8505270 TI - Environmental safety issues for genetically modified animals. AB - Organisms modified by the techniques of modern biotechnology may differ significantly from normal organisms or organisms modified by other methods. Before transgenic organisms are introduced into the environment, the potential environmental effects should be assessed. In general, modification of ecologically important traits in undomesticated species presents the greatest environmental risk. Transgenic livestock probably pose low risk to the environment. Transgenic fish and live virus-based vaccines pose greater risks and present challenging questions for environmental risk assessment. PMID- 8505272 TI - Postoperative Ischemia after cocaine ingestion. AB - Cocaine use has reached epidemic proportions in the United States. Patients may present having ingested cocaine for elective or emergent operative procedures. We report a case of acute myocardial ischemia in a young healthy male patient. PMID- 8505273 TI - Case management. PMID- 8505274 TI - Can defense lawyers still talk to treating physicians about patient information? PMID- 8505275 TI - An update of solid organ transplantation at UAMS. AB - The one year survival for solid organ transplants is 70 to 90%. Encouraged by this success, the University of Arkansas for Medical Sciences is expanding its organ transplant center and will offer renal, pancreas, liver, heart, and lung within a year. The limiting factor in transplants continues to be a shortage of Donor organs and the need for increased referral of potential donors. PMID- 8505276 TI - Diagnosis and treatment of atraumatic vascular insufficiency of the upper extremity: female smoker's syndrome. AB - A retrospective analysis of 30 angiograms in 29 patients performed at Doctor's Hospital since June of 1989 was carried out. Of these, 15 patients with 16 involved extremities presented with no antecedent trauma and significant symptoms of arterial insufficiency with impending digital necrosis. Eleven were female and four were male. Underlying medical problems included renal failure in four, diabetes in two, scleroderma in two and vasculitis in one. A unique group of six patients had no prior underlying medical problems. All six patients were female and all were smokers. A surprisingly high incidence of major arterial occlusion was noted. The radiographic features appeared distinct from the common causes of vascular insufficiency in the hand, that is, Raynaud's, thromboangiitis obliterans (Buerger's disease), and ulnar artery thrombosis from repetitive microtrauma (hypothenar hammer syndrome). This review is intended to discuss the evaluation and management of this group of patients. PMID- 8505277 TI - Cell tropism and HIV infection. PMID- 8505278 TI - HIV and host immune responses in AIDS pathogenesis. PMID- 8505279 TI - The uniqueness of HIV infection. PMID- 8505280 TI - Early infection and serological markers associated with HIV infection. PMID- 8505281 TI - Glutathione S-transferases, structure, regulation, and therapeutic implications. PMID- 8505282 TI - The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. AB - The insulin receptor substrate 1 (IRS1) is a protein that is rapidly phosphorylated on tyrosine by the activated insulin receptor. Syp is a recently discovered, broadly expressed phosphotyrosine (Tyr(P)) phosphatase that contains two Src homology 2 (SH2) domains. We have found that insulin treatment of 3T3-L1 adipocytes leads to complex formation between IRS1 and Syp. Syp was detected in immunoadsorbates of IRS1 from extracts of insulin-treated but not basal cells by both immunoblotting and Tyr(P) phosphatase activity. The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Unlike the receptors for epidermal and platelet derived growth factors, which in their activated state bind to the SH2 domains of Syp and elicit phosphorylation of Syp on tyrosine in intact cells, the Tyr(P) form of the insulin receptor did not bind to the SH2 domains of Syp, and no phosphorylation of Syp on tyrosine was detected in insulin-treated 3T3-L1 adipocytes. In combination with other findings these results indicate that IRS1 functions as a docking protein for SH2 domain-containing proteins participating in signaling from the insulin receptor. PMID- 8505283 TI - Immediate-early transcriptional regulation and rapid mRNA turnover of a putative serine/threonine protein kinase. AB - Serine/threonine protein kinases are important regulators of diverse cellular processes including metabolism, proliferation, and differentiation. We have previously identified the cDNA for a 49-kDa serine/threonine kinase, designated sgk, which is transcriptionally responsive to glucocorticoid hormones and serum in epithelial cells. We report here that sgk expression is also rapidly induced by dexamethasone or serum in Rat2 fibroblasts. Nuclear run-on and Northern blot analysis revealed that the induction of sgk mRNA is an immediate-early transcriptional response to serum stimulation of quiescent fibroblasts, which occurs just after the peak in c-jun transcription. In contrast to the glucocorticoid-stimulated sgk expression in Rat2 fibroblasts, the transcriptional induction of sgk by serum was transient and sgk transcripts decayed with a particularly rapid half-life of 20 min. The rapid turnover of sgk, in combination with its immediate-early transcriptional response to serum, suggests a novel mechanism for responding to mitogenic signals during G0 to S transition and entry into the cell cycle. PMID- 8505284 TI - Residues 2-25 of phospholamban are insufficient to inhibit Ca2+ transport ATPase of cardiac sarcoplasmic reticulum. AB - We have used sarcoplasmic reticulum (SR) vesicles isolated from AT-1 cardiomyocytes to examine the mechanism of phospholamban (PLB) inhibition of the Ca2+ pump of cardiac SR. By immunoblotting with monoclonal antibodies, we observed that these SR vesicles contained a normal amount of the cardiac isoform of the Ca2+ pump (SERCA 2) but only a trace level of PLB. A monoclonal antibody that recognized amino acid residues 9-17 of PLB had no significant effect on Ca2+ transport by AT-1 SR vesicles, but it increased Ca2+ transport into mouse ventricular SR vesicles greater than 10-fold by reversing PLB inhibition of SERCA 2 at low ionized Ca2+ concentration. To further explore the domains of PLB responsible for SERCA 2 inhibition, we examined the effect of a PLB synthetic peptide consisting of amino acid residues 2-25 on Ca2+ uptake by AT-1 SR vesicles. Even at concentrations as high as 0.44 mM, no significant effect of the peptide was observed. Based on these results, we conclude that the cytoplasmic domain of PLB, containing the phosphorylation sites, by itself is insufficient to inhibit the Ca2+ pump and that the transmembrane region, which stabilizes the pentamer, is also essential for Ca2+ transport regulation. PMID- 8505285 TI - The cardiac Na+-Ca2+ exchanger binds to the cytoskeletal protein ankyrin. AB - Na+-Ca2+ exchange is the major pathway of Ca2+ efflux during excitation contraction coupling in cardiac muscle. The Na+-Ca2+ exchanger is present in cardiac transverse tubules with an apparent high density (Frank, J.S., Mottino, G., Reid, D., Molday, R. S., and Philipson, K.D. (1992) J. Cell Biol. 117, 337 345). The mechanism for this localization is unknown but may involve interactions with the cytoskeleton. In the present study, we examined the interaction of the Na+-Ca2+ exchanger with the cytoskeletal protein ankyrin. On immunoblots of isolated canine cardiac sarcolemma, an antibody raised against purified rabbit red blood cell-ankyrin (RBC-ankyrin) recognized a 220-kDa protein, which is the same size as RBC-ankyrin. Alkaline extraction of sarcolemma removed this protein. The Na+-Ca2+ exchange protein, purified from recombinant baculovirus-infected insect cells, bound 125I-labeled-RBC-ankyrin with a KD of 42 +/- 3 nm. 125I-RBC ankyrin was co-precipitated by antibodies to the Na+-Ca2+ exchanger after preincubation with solubilized cardiac sarcolemma. Myocardial ankyrin could be localized to both surface and T-tubular sarcolemma by immunofluorescence techniques. These results demonstrate that the cardiac Na+-Ca2+ exchanger binds ankyrin with high affinity. This interaction may be important for localizing the Na+-Ca2+ exchanger to specific domains of the sarcolemma. PMID- 8505286 TI - Disruption of the dystrophin-glycoprotein complex in the cardiomyopathic hamster. AB - Cardiomyopathies are a diverse group of primary cardiac diseases, most of which have a poorly understood etiology. One type of hereditary cardiomyopathy is caused by defects in the dystrophin gene in Duchenne and Becker muscular dystrophy patients. Our laboratory has identified a complex of dystrophin associated proteins in skeletal and cardiac muscle which span the sarcolemma, linking the subsarcolemmal cytoskeleton to the extracellular matrix. The absence of dystrophin in Duchenne muscular dystrophy patients leads to the loss of dystrophin-associated proteins in both skeletal and cardiac muscle, suggesting that a primary loss of one or more dystrophin-associated proteins might lead to other forms of cardiomyopathy. Here we report the specific deficiency of the 50 kDa dystrophin-associated glycoprotein in cardiac and skeletal muscles of the BIO 14.6 strain of cardiomyopathic hamsters, which experience both autosomal recessive cardiomyopathy and myopathy. Other dystrophin-associated proteins are well preserved in myopathic hamster skeletal muscle, but the link between dystrophin and dystroglycan is disrupted. All dystrophin-associated proteins are decreased in abundance in the cardiomyopathic hamster heart, perhaps explaining why the cardiomyopathy is more severe than the myopathy. Thus, the disruption of the dystrophin-glycoprotein complex may play a role in skeletal and cardiac myocyte necrosis of the cardiomyopathic hamster. PMID- 8505287 TI - Tyrosine 115 participates both in chemical and physical steps of the catalytic mechanism of a glutathione S-transferase. AB - The participation of the hydroxyl group of tyrosine 115 in the catalytic mechanism of isoenzyme 3-3 of rat glutathione (GSH) S-transferase is implicated by x-ray crystallographic analysis of a product complex and confirmed by comparison of the catalytic properties of the native enzyme and the Y115F mutant. Tyrosine 115 is located in domain II of the protein (the xenobiotic substrate binding domain) and is the first residue in this domain to be shown to play a direct role in catalysis. The 1.8-A structure of isoenzyme 3-3 in complex with (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene, one of the diastereomeric products of the reaction of GSH with phenanthrene 9,10-oxide, indicates that the hydroxyl group of Tyr115 is within hydrogen-bonding distance of the 10-hydroxyl group of the bound product and, by implication, is proximal to the oxirane oxygen of the substrate in the Michaelis complex. Site-specific replacement of Tyr115 with phenylalanine has profoundly different effects on catalysis depending on the type of reaction and whether the rate-limiting step in catalysis is a chemical step or a physical step. Stopped flow measurements of the rate constants for product release and viscosity effects on the steady-state kinetics establish that the rate-limiting step in catalysis with phenanthrene 9,10-oxide (kcat = 0.4 s-1) is probably a chemical one, whereas the physical step of product dissociation (koff) is rate-limiting in the reaction of 1-chloro-2,4 dinitrobenzene (kcat = 20 s-1). The Y115F mutant is severely impaired in catalyzing the addition of GSH to phenanthrene 9,10-oxide (kcat = 0.0044 s-1), evidence that the -OH of Tyr115 provides electrophilic assistance in the epoxide ring opening. In contrast, the Y115F mutant is a better catalyst toward 1-chloro 2,4-dinitrobenzene (kcat = 72 s-1) than is the native enzyme. The enhanced rates of product release in the mutant are ascribed to the loss of hydrogen bonds between the -OH of Tyr115 and the side chain -OH and main chain NH of serine 209, interactions that block the channel to the active site or inhibit the segmental motion of the protein. PMID- 8505288 TI - Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. AB - Botulinum neurotoxin serotype F contains the zinc binding motif of zinc endopeptidases. Atomic adsorption analysis of highly purified toxin preparation revealed the presence of one atom of zinc per molecule of toxin, which could be removed with EDTA or o-phenanthroline. The light chain of the neurotoxin was shown to have a zinc-dependent protease activity specific for VAMP/synaptobrevin, an integral membrane protein of synaptic vesicles. Both isoforms of rat VAMP were cleaved at the same site corresponding to the single Gln-Lys peptide bond present in their sequences. This proteolytic activity was inhibited by EDTA, o phenanthroline, and captopril as well as by VAMP peptides spanning the cleavage site. PMID- 8505289 TI - The carboxyl-terminal CXXX sequence of Gi alpha, but not Rab5 or Rab11, supports Ras processing and transforming activity. AB - Although the heterotrimeric Gi alpha subunit terminates in an apparent CXXX prenylation signal (CGLF), it is not modified by isoprenylation. To determine if the Gi alpha CXXX sequence can signal prenylation when placed at the carboxyl termini of normally prenylated proteins, we have characterized the processing and biological activity of chimeric oncogenic Ras proteins that terminate in the Gi alpha CXXX sequence (Ras/Gi alpha). Surprisingly, these chimeras were prenylated both in vivo and in vitro, demonstrated significant membrane association, exhibited transforming activity, and induced transcriptional transactivation from Ras-responsive elements. We then extended these studies to determine if, unlike the CC or CXC carboxyl-terminal sequences of other Rab proteins, the carboxyl terminal CXXX sequences of the Ras-related Rab5 and Rab11 proteins represent conventional CXXX prenylation signals that can support Ras processing and transforming activity. Unexpectedly, these Ras/Rab chimeras were nonprenylated, were cytosolic, and lacked detectable transforming or transcriptional transactivation activity. Taken together, these results suggest that the context within which a CXXX sequence occurs may also critically control the modification of a protein by prenylation, and that the Rab5 and Rab11 carboxyl termini do not possess conventional CXXX sequences. Instead, their CCXX and CCXXX motifs may represent additional classes of protein prenylation signals. PMID- 8505290 TI - Composition of the peptidoglycan of Haemophilus influenzae. AB - The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis. The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained. Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U. (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp. 29 34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D. (1989) J. Biol. Chem. 264, 11093 11098). Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine. The peptidoglycan was 27% cross linked, 2% of which formed between diaminopimelic acid residues. No species was identified containing lysyl-arginine residues characteristic of lipoprotein. The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H. influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers. Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance. PMID- 8505291 TI - Membrane topology of the glucose transporter of Escherichia coli. AB - The glucose transporter of the bacterial phosphotransferase system couples translocation with phosphorylation of the substrate in a 1:1 stoichiometry. It consists of a transmembrane subunit (IIBCGlc) and a hydrophilic subunit (IIAGlc). Both subunits are transiently phosphorylated. The IIBCGlc subunit is 477 residues long and consists of two domains. The amino-terminal hydrophobic domain is involved in glucose binding and translocation, the carboxyl-terminal domain contains the phosphorylation site (Cys421). Protein fusions between IIBCGlc and beta-galactosidase (LacZ) as well as alkaline phosphatase (PhoA) were analyzed to determine the membrane topology of the IIBCGlc subunit. The protein fusions were generated by progressively deleting ptsG from its 3' end and ligating the truncated gene to lacZ and 'phoA lacking promoter and leader sequences. LacZ fusions of high activity (32 out of 54) occur at the amino and carboxyl termini and three internal clusters, and 41 active PhoA fusions occur in four internal clusters. Accordingly the hydrophobic domain of IICGlc (residues 19-336) is suggested to contains eight membrane-spanning segments, with the amino terminus and the COOH-terminal hydrophilic domain (IIBGlc) located on the cytoplasmic face of the membrane. A sequence comparison of IIBCGlc with three related proteins indicates that the periplasmic loops differ in size and sequence while the cytoplasmic loops are better conserved. PMID- 8505292 TI - Cysteine phosphorylation of the glucose transporter of Escherichia coli. AB - The glucose transporter (IIBCGlc/IIAGlc complex) of the bacterial phosphotransferase system couples vectorial translocation to phosphorylation of the transported sugar. The IIAGlc subunit transfers the phosphoryl group from the phosphoryl carrier protein P-HPr to the IIBCGlc subunit. IIBCGlc translocates and phosphorylates glucose. The site of IIBCGlc phosphorylation is cysteine 421 as shown by mass spectrometric and biochemical analyses of phosphorylated peptides. Site-directed mutagenesis of Cys421 (C421S) afforded a stable but completely inactive protein (Nuoffer, C., Zanolari, B., and Erni, B. (1988) J. Biol. Chem. 263, 6647-6655). Cys421 is located in the C-terminal cytoplasmic domain of the IIBCGlc subunit in a sequence context (LDACITRL) which is well conserved in other transporters of the bacterial phosphotransferase system. Phosphocysteine has been shown previously to be the catalytic intermediate of the mannitol transporter (Pas, H. H., Meyer, G. H., Kruizinga, W. H., Tamminga, K. S., van Weeghel, R. P., and Robillard, G. T. PMID- 8505293 TI - Cloning and sequencing of the genes coding for the A and B subunits of vacuolar type Na(+)-ATPase from Enterococcus hirae. Coexistence of vacuolar- and F0F1-type ATPases in one bacterial cell. AB - The eubacterium Enterococcus hirae ATCC 9790 possesses a H(+)-translocating ATPase, and the deduced amino acid sequences of the genes coding for this enzyme have indicated that it is a typical F0F1-type ATPase (Shibata, C., Ehara, T., Tomura, K., Igarashi, K., and Kobayashi, H. (1992) J. Bacteriol. 174, 6117-6124). We cloned the ntpA and ntpB genes coding for the A and B subunits, respectively, of Na(+)-translocating ATPase from the same bacterium, and the full amino acid sequences of the two subunits were deduced from the nucleotide sequence. The A (593 amino acid residues) and B (458 amino acid residues) subunits were highly homologous (48-60% identical) to the A (large or alpha) and the B (small or beta) subunits, respectively, of vacuolar-type H(+)-ATPases which have been found in eukaryotic endomembrane systems (Neurospora crassa, Saccharomyces cerevisiae, Arabidopsis thaliana, and carrot) and archaebacterial cell membranes (Sulfolobus acidocaldarius and Methanosarcina barkeri). The A and B subunits of Na(+)-ATPase showed about 23-28% identities with the beta and alpha subunits of E. hirae F1 ATPase and of Escherichia coli F1-ATPase, respectively. These results indicate that E. hirae Na(+)-ATPase belongs to the vacuolar-type ATPase. This is the first demonstration that both genes for V- and F-type ATPases are functionally expressed in one bacterial cell. PMID- 8505294 TI - Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes. AB - A reaction between enzyme renin and its only natural substrate angiotensinogen is the initial and rate-limiting step for producing a potent vasoconstrictor angiotensin II as the final product of the renin-angiotensin system, a contributory factor in the pathogenesis of hypertension. In order to assess the role of the interaction of human renin with human angiotensinogen in the development of high blood pressure, we have constructed the chimeric renin angiotensin cascade in mice comprising both human renin and human angiotensinogen as well as the endogenous angiotensin-converting enzyme and angiotensin II receptor by cross-mating separate lines of transgenic mice carrying either the human renin or human angiotensinogen genes. Although each single gene carrier did not develop hypertension despite the observed normal tissue-specific expression of the transgenes, dual gene strains exhibited a chronically sustained increase in blood pressure. Administration of a human renin-specific inhibitor (ES-8891) was effective in reducing the elevated blood pressure only against the cross mated hybrid mice, but treatment of an angiotensin-converting enzyme inhibitor (captopril) and a selective antagonist (DuP 753) directed at the angiotensin II receptor decreased the basal level of blood pressure even in single gene carriers as well as in dual gene mice. These results clearly demonstrated that the sustained increase in blood pressure of the hybrid mice was initiated by the interaction between the products of the two human genes. PMID- 8505295 TI - Visual arrestin interaction with rhodopsin. Sequential multisite binding ensures strict selectivity toward light-activated phosphorylated rhodopsin. AB - Visual arrestin plays an important role in regulating light responsiveness via its ability to specifically bind to the phosphorylated and light-activated form of rhodopsin. Previously, we utilized an in vitro translation system to express and characterize the full-length (404 amino acids) and two truncated forms of visual arrestin. Here we have extended these studies to include a total of 33 different truncation and deletion mutants of arrestin, ranging from 69 to 391 amino acids in length. Mutants were produced by cutting within the open reading frame of the bovine arrestin cDNA with selective restriction enzymes followed by in vitro translation of the transcribed truncated mRNAs. Mutant arrestin binding to dark, light-activated, dark phosphorylated, and light-activated phosphorylated rhodopsin as well as to opsin, phosphoopsin, and truncated rhodopsin was then extensively characterized. In addition, the sensitivity of arrestin/rhodopsin interactions to conditions of increasing ionic strength was measured. These studies suggest the localization of multiple functional domains within the arrestin molecule that include: 1) a "phosphorylation recognition" domain, which interacts with the phosphorylated carboxyl terminus of rhodopsin, was localized predominately between residues 158-185; 2) an "activation recognition" domain, which interacts with those portions of the rhodopsin molecule that change conformation upon light activation, was found to consist of at least three regions within the first 191 residues of the arrestin molecule; 3) a hydrophobic interaction domain, localized between residues 191 and 365, appears to be mobilized upon binding of arrestin to activated phosphorylated rhodopsin; 4) a regulatory domain, localized in the COOH-terminal region of arrestin (residues 365-391), was found to play a role in controlling the conformational change in arrestin necessary for mobilization of the hydrophobic interaction domain; and 5) The NH2 terminus of arrestin (residues 2-16) was found to be important for interacting with the regulatory COOH-terminal region as well as maintaining the conformation of the NH2-terminal half of arrestin. A mechanism which ensures strict arrestin binding selectivity toward phosphorylated light-activated rhodopsin is proposed. PMID- 8505296 TI - Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation. AB - Membrane-bound enzymatic systems obtained from maize embryos that catalyze the oxidative C4-monodemethylation of 4,4-dimethyl- and 4 alpha-methylsterols have been investigated. Enzymatic assay conditions have been developed for the first time to detect the C4-monodemethylated products formed. The properties of the microsomal systems have been established for co-factor requirements and kinetics. The demethylation process has been interrupted to demonstrate the formation of stable, oxygenated intermediates. In addition to the 3-keto and 3 beta-hydroxy-4 monodemethylated products formed, three new sterols have been identified. 3 beta Hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo-24(24(1))-en-4 alpha-hydroxy methyl was identified for the first time as the immediate metabolite of 24-methylenecycloartanol by 4 alpha-methyl oxidase in addition to 3 beta-hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo- 24(24(1)) en-4 alpha-carboxylic-acid and 3 beta-hydroxy-5 alpha-stigmasta-7,24(24(1))-dien 4 alpha-carboxylic-acid, intermediates involved respectively in the oxidative demethylation of 24-methylenecycloartanol and 24-ethylidenelophenol. Proton nuclear magnetic resonance studies of enzymatically produced 3 beta-hydroxy-4 beta,14 alpha-dimethyl-5 alpha-ergosta-9 beta,19-cyclo-24(24(1))en-4 alpha carboxylic acid indicate that the 4 alpha-methyl group of 24 methylenecycloartanol is oxidized and subsequently removed during its enzymatic conversion to cycloeucalenol. From a series of incubations with 25 natural or synthetic 4,4-dimethyl and 4 alpha-methylsterols, a high degree of substrate specificity for the oxidation at C4 of 4,4-dimethyl- and 4 alpha-methylsterols was determined. Our results indicate that oxidation of the 4 alpha-methyl group of the 4,4-geminal dimethylsterols requires the more flexible and presumably bent conformation of 9 beta,19-cyclopropylsterols and the absence of a delta 24(25) unsaturation, whereas the rigid planar conformation of delta 7-unsaturated sterols favors oxidation of 4 alpha-methylsterols. Distinct strict structural requirements for the oxidation of 4,4-dimethyl- and 4 alpha-methylsterols and different sensitivity toward cyanide ions and 3 beta,5 alpha,6 alpha stigmastatriol, a novel inhibitor of 4 alpha-methylsterol C4 oxidase activity, are consistent with the conclusion that two distinct oxidative systems are involved in the removal of the first and second C4-methyl group of phytosterol precursors. Moreover, the present study directly establishes that during the conversion of cycloartenol to phytosterol one C4 dealkylation occurs before the removal of the 14 alpha-methyl group. PMID- 8505297 TI - Long and very long chain polyunsaturated fatty acids of the n-6 series in rat seminiferous tubules. Active desaturation of 24:4n-6 to 24:5n-6 and concomitant formation of odd and even chain tetraenoic and pentaenoic fatty acids up to C32. AB - The formation of long and very long chain (VLC) n-6 polyunsaturated fatty acids (PUFA) in isolated rat seminiferous tubules was investigated by following the metabolism of three 1-14C-labeled n-6 tetraenoic fatty acids (20:4, 24:4, and 32:4) and [U-14C]acetate. In contrast to [14C]32:4, which was poorly incorporated and altered, [14C]20:4 and [14C]24:4 were efficiently taken up by the tubules, esterified into lipids, elongated to VLCPUFA, and desaturated to pentaenoic fatty acids; the rate of [14C]24:4 desaturation to [14C]24:5 was notably high. The main products with [14C]acetate as precursor were labeled saturates and VLCPUFA, most of the label in tetraenoic and pentaenoic acids appearing in 24:4 and 24:5, respectively. These two C24 polyenes, connected by a delta 6 desaturation, may play a central role in n-6 PUFA metabolism, in their capacity as potential precursors of longer polyenes via elongation and of shorter ones, such as 22:5n 6, via retroconversion. Triacylglycerols, rich in C22 and C24 polyenes, incorporated the greatest amounts of both [14C] acetate-derived and exogenous 14C PUFA, suggesting that this lipid class is involved in the traffic and metabolism of testicular PUFA. The detection of a series of unusual odd-chain tetraenoic and pentaenoic acids, also labeled with [U-14C]acetate, suggests that a PUFA chain shortening mechanism occurs in testis involving alpha- in addition to beta oxidation. We speculate that alpha-oxidation plays a role in the retroconversion of PUFA. PMID- 8505298 TI - Immunological analysis of GLUT4-enriched vesicles. Identification of novel proteins regulated by insulin and diabetes. AB - In adipocytes and muscle, insulin stimulates the translocation of glucose transporter proteins from an intracellular vesicle pool to the plasma membrane. To study the molecular basis of this process, we used the anti-GLUT4 antibody 1F8 to isolate intracellular vesicles from rat adipocytes that are enriched in the muscle/fat glucose transporter isoform. These vesicles were then used as immunogens to generate monoclonal antibodies against their protein components. We isolated an antibody, 3F8, that recognizes three polypeptides, designated GTV3, migrating in the 36-40-kDa range as analyzed by SDS-polyacrylamide gel electrophoresis and Western blotting. These proteins are enriched in GLUT4 containing vesicles, and the two smallest of the polypeptides recognized by 3F8 translocate to the cell surface in response to insulin. GTV3 proteins are also present in plasma membranes of fat cells and liver as well as in a wide number of tissues, red blood cells being the only exception. In adipocytes from streptozotocin-induced diabetic rats, GTV3 protein levels decrease dramatically and return to normal levels when animals are treated with insulin. The localization of GTV3 in glucose transporter-containing vesicles as well as their wide tissue distribution suggests that these proteins may be involved in vesicle mediated transport and regulated trafficking between membrane compartments. PMID- 8505299 TI - Characterization of hormonally regulated and particulate-associated phospholipase A2 from bovine endothelial cells. AB - Hormonally regulated and particulate-associated phospholipase A2 (PLA2) was detected in endothelial cells from bovine pulmonary artery. The enzyme was solubilized and subjected to initial characterization. PLA2 activity was determined in subcellular fractions from bradykinin (BK)-stimulated and nonstimulated cells by following the release of arachidonic acid (AA) from exogenously added 1-palmitoyl-2-[1-14C]arachidonoyl-phosphatidylcholine. Stimulation of cells with BK led to increased PLA2 activity in a particulate fraction (the 92,000 x g pellet of the postnuclear supernatant). The activity in the cytosolic fractions from BK-stimulated and nonstimulated cells was the same. The association of the hormonally regulated PLA2 (HR-PLA2) activity with the particulate fraction was not affected by decreasing the Ca2+ concentrations in the homogenate from 7 microM to 33 nM and therefore was not induced during homogenization by the presence of Ca2+ in the homogenate. The HR-PLA2 activity was Ca(2+)-dependent and was maximal at submicromolar concentrations of Ca2+. Incubation of the particulate fraction obtained from BK-stimulated and nonstimulated cells with 10 mM n-octyl-beta-D-glucopyranoside resulted in a differential solubilization of the HR-PLA2 activity. Its isoelectric point was determined to be 5.7. HR-PLA2 activity in the octyl glucoside extract of the particulate fraction from stimulated cells co-sedimented in sucrose gradients with the cytosolic PLA2. Their molecular mass was estimated to be 103,000 Da. The extracted enzyme from BK-stimulated cells retained its increased activity toward 1-palmitoyl-2-[1-14C]arachidonoyl-phosphatidylcholine. However, its activity toward 1-palmitoyl-2-[1-14C]oleoyl-phosphatidylcholine was equal to the PLA2 activity extracted from nonstimulated cells. Treatment of the cells with 100 nM 12-O-tetradecanoylphorbol-13-acetate resulted in a 20 +/- 1.2% (mean +/- S.E., p < 0.01, n = 4) increase in the PLA2 activity in the cytosol but failed to increase PLA2 activity in the particulate fraction. In contrast, addition of 7 microM Ca2+ ionophore A23187 resulted in a 21 +/- 0.55% (mean +/- S.E., p < 0.01, n = 5) decrease in the cytosolic activity and a concomitant increase of 68 +/- 9.6% (mean +/- S.E., p < 0.05, n = 5) in the particulate-associated activity. We conclude that stimulation of endothelial cells with BK increases the activity of a Ca(2+)-sensitive high molecular weight isoform of PLA2 which is associated with the particulate fraction. Possible mechanisms of activation are discussed. PMID- 8505300 TI - On the mechanism of frameshift (deletion) mutagenesis in vitro. AB - An experimental system has been developed to quantify frameshift deletions and base substitutions formed during DNA synthesis in vitro. Oligodeoxynucleotides, modified site-specifically with acetylaminofluorene or other adducts and lesions, were used as templates in primer extension reactions catalyzed by the Klenow fragment of Escherichia coli DNA polymerase I. The influence of DNA sequence context on frameshift mutagenesis was determined by modifying systematically the bases flanking the lesion. Frequencies of nucleotide insertion opposite the lesion and chain extension from the 3'-primer terminus were established by steady state kinetic analysis. The ability of a damaged nucleotide to generate one-base and two-base frameshift deletions was determined primarily by two parameters: the nature of the base inserted opposite the adduct with respect to the sequence context in which the lesion is embedded and the overall rate of translesional DNA synthesis. Frameshift deletions generated during DNA synthesis were greatly enhanced in the absence of proofreading exonuclease. Misinsertion of bases opposite the lesion precedes misalignment of the template-primer. Extending on earlier studies (Kunkel, T. A. (1990) Biochemistry 29, 8003-8011), a model has been proposed and used in various sequence contexts to predict the propensity of aminofluorene adducts, exocyclic DNA adducts, 8-oxopurines, and synthetic abasic sites to generate frameshift deletions in vitro. PMID- 8505301 TI - Monomers of human beta 1 beta 1 alcohol dehydrogenase exhibit activity that differs from the dimer. AB - A previously unreported enzymatic activity is described for monomers of the beta 1 beta 1 isoenzyme of human alcohol dehydrogenase that were prepared from dimeric enzyme by freeze-thaw in liquid nitrogen. Whereas the dimeric enzyme has optimal activity at low substrate concentrations (2.5 mM ethanol, 50 microM NAD+; "low Km" activity), the monomer has its highest activity at high substrate concentrations (1.5 M ethanol, 2.5 mM NAD+; "high Km" activity). While the activity of the monomer does not appear to be saturated at 1.5 M ethanol, its maximal activity at this high ethanol concentration exceeds the Vmax of the dimer by about 3-fold. The apparent Km of NAD+ with monomers is 270 microM, and no activity could be detected with nicotinamide mononucleotide as cofactor. During gel filtration the high Km activity elutes at a lower apparent molecular weight position than the dimer. The kinetics of monomer-to-dimer reassociation are consistent with a second-order process with a rate constant of 240 M-1 s-1. The reassociation rate is markedly enhanced by the presence of NAD+. During refolding of beta 1 beta 1 following denaturation in 6 M guanidine hydrochloride, an enzyme species with high Km activity and spectral properties similar to the freeze-thaw monomer is observed, indicating that a catalytically active monomer is an intermediate in the refolding pathway. The enzymatic activity of the monomer implies that the intersubunit contacts of beta 1 beta 1 are not crucial in establishing a catalytically competent enzyme. However, the differences in specific activity and Km between monomer and dimer suggest that dimerization may serve to modulate the catalytic properties. PMID- 8505303 TI - DNA polymerase III accessory proteins. I. holA and holB encoding delta and delta'. AB - The genes encoding the delta and delta' subunits of the 10-subunit Escherichia coli replicase, DNA polymerase III holoenzyme, have been identified and sequenced. The holA gene encoding delta is located downstream of rlpB at 15.2 min and predicts a 38.7 kda protein. The holB gene encoding delta' is located at 24.3 min and predicts a 36.9-kDa protein. Hence the delta and delta' subunits are unrelated proteins encoded by separate genes. The genes have been used to express and purify delta and delta' in quantity. The predicted amino acid sequence of delta' is homologous to the sequences of the tau and gamma subunits revealing a large amount of structural redundancy within the holoenzyme. PMID- 8505302 TI - Apical secretion of a cytosolic protein by Madin-Darby canine kidney cells. Evidence for polarized release of an endogenous lectin by a nonclassical secretory pathway. AB - In the classical secretory pathway proteins containing a signal peptide are translocated from the cytoplasm of the cell into the lumen of the endoplasmic reticulum (ER). From the ER they are transported to the Golgi apparatus and finally to the plasma membrane (PM) where they are released into the extracellular compartment. However, some proteins are synthesized without a signal peptide and maintain a predominantly cytosolic distribution until they are released from the cell. As a marker for this nonclassical secretory pathway we have chosen L-29, a soluble lectin of M(r) about 29,000, that has affinity for lactose and other beta-galactoside containing glycoconjugates. We were interested in determining if cultured epithelial cells secrete L-29 and if they do so in a polarized fashion. Madin-Darby canine kidney (MDCK)-II cells were found to express large quantities of L-29 (about 1% of the detergent soluble protein). The lectin was diffusely distributed in the cytosol, with little or none in vesicular compartments. The polarity of L-29 secretion, when analyzed in pulse-chase experiments, was selectively into the apical compartment of filter-grown MDCK cells. This secretion was not inhibited by brefeldin A or monensin, drugs that are known to inhibit protein transport through the ER-Golgi-PM pathway. Secretion of L-29 was augmented 3-5-fold by the calcium ionophore A23187 and by increasing the temperature to 42 degrees C, whereas lowering the temperature to 20 degrees C or addition of nocodazole prevented secretion. These results demonstrate the polarized secretion of a cytosolic protein by a nonclassical secretory pathway. PMID- 8505304 TI - DNA polymerase III accessory proteins. II. Characterization of delta and delta'. AB - The gamma complex subassembly (gamma delta delta' chi psi) of DNA polymerase III holoenzyme couples ATP to assemble the ring-shaped beta subunit around DNA forming a DNA sliding clamp. This beta clamp is needed for highly processive synthesis by the holoenzyme. Here, the delta and delta' subunits of the gamma complex are studied for their structural and functional interaction with each other and with the gamma subunit. Both delta and delta are monomeric in their native state, and they bind each other tightly to form a 1:1 complex. Neither delta nor delta' alone binds tightly to the gamma subunit. However, as a complex, delta delta' binds gamma tightly to form a gamma delta delta' complex. The fact that all three subunits, gamma, delta, and delta', are needed to form a tight complex correlates well with activity assays which show that gamma and delta are capable but inefficient in assembly of the beta ring onto DNA and delta' is needed for an efficient reaction. PMID- 8505305 TI - DNA polymerase III accessory proteins. IV. Characterization of chi and psi. AB - The gamma complex (gamma delta delta' chi psi) subassembly of the Escherichia coli replicase initiates processive replication upon assembling the ring-shaped beta subunit around DNA. The beta ring acts as a clamp to hold the replicase down to DNA for highly processive synthesis. In this report we characterize the chi and psi subunits of the gamma complex. Both chi and psi are monomeric, and they associate to form a 1:1 complex. The chi subunit does not form a complex with gamma, but psi binds gamma tightly thereby acting as a bridge to assimilate chi into the gamma complex structure. The psi subunit stimulated the ATPase and replication activities of gamma. The chi subunit only stimulated the activities of gamma when the psi subunit was also present thus reflecting the structure where psi bridges the interaction of chi with gamma. PMID- 8505306 TI - DNA polymerase III accessory proteins. V. Theta encoded by holE. AB - The polIII core subassembly of DNA polymerase III holoenzyme is composed of the alpha (DNA polymerase), epsilon (editing exonuclease), and theta subunits. We have identified holE encoding theta (8.6 kDa) at 40.4 min, expressed and purified 300 mg of theta, and have studied its function by constituting the polIII core from pure alpha, epsilon, and theta subunits. The theta subunit binds the epsilon proofreader tightly, but it does not form a detectable complex with alpha. The epsilon subunit also binds to alpha (Maki, H., and Kornberg, A. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 4389-4392). Hence, the subunit arrangement of the polIII core is linear, alpha epsilon theta. Interaction of theta with epsilon slightly stimulated epsilon in excision of a 3' terminal mismatched nucleotide, suggesting a possible role for theta in fidelity. PMID- 8505307 TI - Characterization of yeast plasma membrane H(+)-ATPase mutant pma1-A135V and its revertants. AB - An A135V substitution in the first transmembrane segment of the yeast plasma membrane H(+)-ATPase (PMA1) confers cellular resistance to hygromycin B, exhibits growth sensitivity to low external pH, and results in a defective enzyme that hydrolyzes ATP at 33% of wild type level. The importance of the A135 residue was probed genetically by analysis involving both site-directed mutagenesis and randomly generated second-site intragenic suppressor mutations. No other amino acid at position 135 gave either the wild type phenotype or the normal enzyme activity of A135. Substitutions with the bulkier amino acid residues A135L, A135I, and A135F produced more severe cellular phenotypes than the original A135V mutation. The substitution of the smaller side chain residue Gly was also a mutant, although not as severe as the A135V mutant. The introduction of a bulky Trp or a polar Ser residue produced dominant lethality, while charged amino acids produced recessive lethality. Reduced rates of proton transport measured by acidification of the medium by whole cells correlate closely with the severity of cellular phenotype. Some of the mutant enzymes exhibit an apparent instability in vitro. Thus, the localized structure around A135 is highly constrained. The cellular sensitivity to low external pH of the A135V mutant was used to select intragenic revertants. Most full revertants (low pHR, HygS) restored A135, but second-site mutations in putative transmembrane segments 2 (V146I and V157F) and 4 (L327V) were also observed. Two partial revertants (low pHR, HygR) have secondary mutations at S660C or a double change at F611L-S660F in the putative ATP binding domain. These results provide additional evidence for functional coupling between the cytoplasmic domain catalyzing ATP hydrolysis and transmembrane helices 1 and 2. PMID- 8505308 TI - Vaccinia virus RNA helicase. Directionality and substrate specificity. AB - Vaccinia virus RNA helicase (NPH-II) catalyzes unidirectional unwinding of 3' tailed duplex RNAs in the presence of a divalent cation and any one of the eight common nucleoside triphosphates (NTP). The helicase binds stably to the tailed RNA in the absence of any cofactor; strand displacement by the bound protein is coupled to NTP hydrolysis. Although the helicase is capable of binding to tailed duplex DNA as well as to tailed RNA, the enzyme is unable to unwind duplex DNA. It is suggested that NTP hydrolysis by RNA-bound NPH-II drives processive translocation of the protein in a 3' to 5' direction along the RNA strand, whereas energy utilization by DNA-bound enzyme leads to dissociation without extensive protein movement. A role for the RNA helicase in vaccinia mRNA synthesis is proposed. PMID- 8505310 TI - Thrombin is inactivated by mast cell secretory granule chymase. AB - In a recent paper we demonstrated that cultures of murine adherent peritoneal cells expressed cell surface-associated serine protease activity that specifically inactivated thrombin by cleaving the enzyme into defined proteolytic fragments (Pejler, G., and Seljelid, R. (1992) J. Biol. Chem. 267, 3136-3142). In the present report, the purification and further characterization of the thrombin inactivating serine protease is described. The serine protease is shown to be expressed by mast cells. Purification of the thrombin-inactivating serine protease by a combination of anion-exchange chromatography and Superdex 75 chromatography showed that the enzyme had an apparent molecular mass of 28 kDa. N terminal sequence analysis of the purified protein demonstrated 100% identity of the thrombin-inactivating serine protease with the secretory granule chymases: murine mast cell protease 3 and murine mast cell protease 4. The serine protease showed chymotrypsin-like substrate specificity. The thrombin-inactivating activity was markedly enhanced by optimal concentrations of heparin. PMID- 8505309 TI - Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. AB - Many effects of lipopolysaccharide (LPS) on gene expression, including that of human immunodeficiency virus (HIV), in monocytic cells are mediated by activation of kappa B DNA-binding proteins. However, the specific members of the NF-kappa B/Rel transcription factor family involved in the LPS response, and the mechanisms through which LPS-generated signals are transduced remain unclear. Here we show that LPS induces nuclear expression of c-Rel/p50 heterodimers as well as p50/p65 (NF-kappa B) kappa B DNA-binding complexes in human monocytic THP 1 cells. Nuclear localization of these proteins occurred concomitantly with a rapid decrease in their cytosolic levels and was independent of phorbol ester sensitive protein kinase C. Within 24 h following LPS stimulation there was a striking increase in the levels of c-Rel, p105, and p50 in the cytosol. The increased levels of these proteins correlated with increases in the amounts of their mRNAs during LPS activation of THP-1 cells. LPS activation of THP-1 cells resulted in phosphorylation of MAD3 (an I kappa B-like protein), a rapid increase in MAD3 mRNA, and an increase in MAD3 protein by 2 h. Thus, LPS activation of human monocytic cells results in nuclear expression of c-Rel/p50 and p50/p65 (NF kappa B) and induces phosphorylation of MAD3. PMID- 8505311 TI - Bidirectional excision in methyl-directed mismatch repair. AB - Using electron microscopy and indirect end-labeling methods, we have examined excision tracts produced by the Escherichia coli methyl-directed mismatch repair system on a closed circular G-T heteroduplex that contains a single d(GATC) site. Despite differing polarities of the unmodified strand in the two hemimethylated derivatives of the heteroduplex, that portion of the unmethylated strand spanning the shorter path between the d(GATC) site and mismatch is targeted for excision in both cases. Mismatch-provoked excision occurring on both hemimethylated DNAs requires DNA helicase II, but exonuclease requirements for the reaction depend on heteroduplex orientation. When the d(GATC) sequence on the unmodified strand resides 3' to the mismatch as viewed along the shorter path, excision requires exonuclease I. Excision occurring on the alternate hemimethylated heteroduplex depends on the 5'--> 3' hydrolytic activity of exonuclease VII. Coupled with the previous demonstration that repair initiates via the mismatch-provoked, MutHLS dependent incision of the unmethylated strand at a d(GATC) sequence (Au, K.G., Welsh, K., and Modrich, P. (1992) J. Biol. Chem. 267, 12142-12148), these findings indicate an excision mechanism in which helicase II displacement renders the incised strand sensitive to the appropriate single-strand exonuclease. Our data imply that hydrolysis commences at the d(GATC) site, proceeds to a point beyond the mismatch, and terminates at a number of discrete sites within a 100 nucleotide region just beyond this site. The extent of excision is therefore controlled by one or more components of the repair system. PMID- 8505312 TI - Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction. AB - Nuclear extracts prepared from a HeLa cell line have been previously shown to support strand-specific repair of heteroduplex DNAs containing a site-specific, strand-specific incision (Holmes, J.J., Clark, S., and Modrich, P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5837-5841; Thomas, D.C., Roberts, J.D., and Kunkel, T.A. (1991) J. Biol. Chem. 266, 3744-3751). Further analysis of the substrate specificity of the reaction has shown that in addition to G-T, A-C, G-G, and C-C, nuclear extracts also recognize and correct in a strand-specific manner A-A, A-G, T-T, and C-T mismatches, with repair in each case being inhibited by aphidicolin. The rate of repair of a circular G-T heteroduplex was found to decrease monotonically with increasing separation between the mismatch and the strand break that targets repair, as viewed along the shorter path joining the two sites in the circular substrate. This decrease is independent of the polarity of the incised strand, suggesting that the human pathway of mismatch correction may possess a bidirectional excision capability similar to that of the Escherichia coli methyl-directed system. This possibility was confirmed by analysis of excision tracts associated with the reaction. Inhibition of DNA synthesis by aphidicolin or by omission of exogenous dNTPs leads to the mismatch-provoked formation of a single-strand gap that spans the shorter path between the strand break and the mismatch, irrespective of the polarity of the incised strand. Formation of these gaps, which extend from the site of the strand break to terminate at a number of discrete sites in the region 90 to 170 nucleotides beyond the mismatch, is therefore independent of the relative orientation of the two sites. Based on similar mismatch specificities and common features of mechanism, we have concluded that the human strand-specific mismatch repair system is functionally homologous to the bacterial methyl-directed pathway. PMID- 8505313 TI - Phorbol ester stimulates the activity of a protein tyrosine phosphatase containing SH2 domains (PTP1C) in HL-60 leukemia cells by increasing gene expression. AB - The affinity-purified antibody to a protein tyrosine phosphatase (PTP) containing two src homology 2 domains (PTP1C) was generated. The antibody recognized two types of PTP1C (PTP1C-alpha and -beta) of which the molecular sizes were 66 (alpha) and 62 kDa (beta), respectively, and these two types were expressed differentially in various cell types. The immune complex phosphatase assay using the antibody demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) and a vitamin D metabolite increased the PTP activity of immunoprecipitated PTP1C to 230 and 150% of control, respectively. By contrast, neither dimethyl sulfoxide nor retinoic acid significantly affected the PTP activity of PTP1C in HL-60 cells. The time course increment by TPA of PTP1C activity was closely correlated with that of the acquisition by HL-60 cells of a macrophage-like phenotype. In addition, TPA increased the amount of PTP1C detected by immunoblotting and immunoprecipitation and raised the level of expression of PTP1C mRNA in HL-60 cells. The increase of PTP1C mRNA induced by TPA treatment was inhibited by cycloheximide, suggesting that new protein synthesis is required for the increase by TPA of PTP1C mRNA expression. Furthermore, TPA increased the rate of transcription of the PTP1C gene without affecting the stability of PTP1C mRNA. These results suggest that (i) two subtypes of PTP1C may exist and function in various cell types, and (ii) TPA stimulates the PTP activity of PTP1C by increasing the transcription rate of PTP1C gene expression. The possible role of PTP1C in the macrophage differentiation will be also discussed. PMID- 8505314 TI - The structure and dynamics of the granulocyte macrophage colony-stimulating factor receptor defined by the ternary complex model. AB - Myeloid cell lines and primary leukemic myeloblasts express two classes of granulocyte macrophage colony-stimulating factor (GM-CSF) binding sites of high (Kd 20-50 pM) and low affinity (Kd 5-10 nM). High affinity binding is caused by the association of two chains, p80 alpha and p130 beta, whereas p80 alpha alone confers low affinity binding only. Furthermore interleukin-3 (IL-3) competes for the binding of GM-CSF to its high affinity receptor (for review see Nicola, N. A., and Metcalf, D. (1991) Cell 67, 1-4). In the present study, we took advantage of the perturbation of GM-CSF binding equilibrium by IL-3 to take a quantitative approach to analysis of the structure and dynamics of the GM-CSF receptor complex. First, cross-linking studies were performed at two concentrations of radioligand. At 200 pM, a concentration sufficient for near saturation of the high affinity binding site R1, the association between p80 alpha and p130 beta is stoichiometric, and the addition of IL-3 prevents the binding to both chains. At 5 nM, a concentration sufficient for half-occupancy of the low affinity binding site R2, IL-3 prevents cross-linking to the beta chain only. Second, GM-CSF saturation curves were analyzed both at equilibrium and under conditions of perturbation of the equilibrium by IL-3. In the presence of IL-3, the interaction of GM-CSF with its receptor is converted from high to low affinity binding. Computer modeling of binding data with a ternary complex model involving GM-CSF, p80 alpha, and p130 beta indicates that the model fits the data with accuracy and suggests that ligand binding stabilizes the interaction between p80 alpha and p130 beta by 3 orders of magnitude. Third, membrane solubilization dissociates p80 alpha and p130 beta whereas on ligand-stabilized preformed complexes, solubilization did not dissociate the two chains. Finally, upon addition of GM CSF, there is an increase with time in the proportion of ligand bound to the high affinity receptor, at the expense of that bound to low affinity receptor, suggesting that stabilization of the ternary complex is a time-dependent process. PMID- 8505315 TI - J1-crystallins of the cubomedusan jellyfish lens constitute a novel family encoded in at least three intronless genes. AB - The transparent cellular eye lens of the jellyfish (Tripedalia cystophora) contains three major proteins called J1-, J2-, and J3-crystallins. Here we have isolated cDNAs encoding three novel 37-kDa J1-crystallin polypeptides (J1A, J1B, and J1C) sharing 84-98% identity in amino acid sequence among themselves. Each polypeptide is encoded in a separate gene lacking introns. In contrast to the striking similarity of the coding regions, the 5'- and 3'-untranslated sequences of the three J1-crystallin mRNAs are completely different, consistent with an ancient duplication of their genes. Thermostability experiments showed that J1 crystallins remain soluble at 50 degrees C, but precipitate at 60 degrees C, suggesting that these major lens proteins are neither heat shock proteins nor unusually heat-resistant as are many vertebrate crystallins. Although J1 mRNAs appear polyadenylated, no typical polyadenylation signal was detected in the cDNAs. Surprisingly, the only obvious similarities among the 5'-flanking regions of the three J1-crystallin genes are putative TATA boxes and several CAAT sequences, consistent with fewer evolutionary constraints on the regulatory sequences than on the coding sequences of these crystallin genes. PMID- 8505316 TI - Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells. AB - Eukaryotic translation initiation factor 4E (eIF-4E) is one component of the m7G cap-binding protein complex eIF-4F and is required for cap-dependent translation initiation. The phosphorylation state of eIF-4E correlates with increased activity and a major phosphorylation site resides at serine 53. To further evaluate the role of eIF-4E phosphorylation, eIF-4E wild-type and two Ser53 mutants, Ser53Ala and Ser53Asp, were expressed at high level, representing almost 2% of the total cell protein, by transient transfection of COS-1 monkey cells. 32PO4 metabolic labeling of transfected cells demonstrated both Ser53 mutants were phosphorylated at an alternate serine residue. [35S]Methionine pulse labeling demonstrated that the wild-type and both Ser53 mutants were equally incorporated into the eIF-4F complex. The effect of wild-type and Ser53 mutant overexpression on cap-dependent translation initiation and internal translation initiation was monitored by cotransfection with an expression vector encoding a dicistronic mRNA for which the 5' cistron is translated in a cap-dependent manner, and the 3' cistron is translated by internal ribosome binding. Unexpectedly, overexpression of the wild-type or either mutant did not affect the efficiency of either cap-dependent or internal initiation. These results demonstrate that phosphorylation of eIF-4E at residue 53 is not required for interaction with p220 and suggest that Ser53 phosphorylation may not be required for cap-dependent translation initiation in this system. PMID- 8505317 TI - Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization. AB - Human cDNAs for cytosolic and mitochondrial serine hydroxymethyltransferase (SHMT) were cloned by functional complementation of an Escherichia coli glyA mutant with a human cDNA library. The cDNA for the cytosolic enzyme encodes a 483 residue protein of M(r) 53,020. The cDNA for the mitochondrial enzyme encodes a mature protein of 474 residues of M(r) 52,400. The deduced protein sequences share a high degree of sequence identity to each other (63%), and the individual isozymes are highly homologous to the analogous rabbit liver cytosolic (92% identity) and mitochondrial (97% identity) SHMT isozymes (Martini, F., Angelaccio, S., Pascarella, S., Barra, D., Bossa, F., and Schirch, V. (1987) J. Biol. Chem. 262, 5499-5509; Martini, F., Maras, B., Tanci, P., Angelaccio, S., Pascarella, S., Barra, D., Bossa, F., and Schirch, V. (1989) J. Biol. Chem. 264, 8509-8519). SHMT is a highly conserved protein with the human isozymes retaining about 43% sequence identity with the E. coli protein. The human cytosolic and mitochondrial SHMT genes were localized to chromosome regions 17p11.2 and 12q13, respectively. The high degree of nucleotide sequence identity between the two isozymes, and the presence of keratin genes in both chromosomal regions, is consistent with these regions of chromosome 12 and 17 arising by a duplication event. PMID- 8505318 TI - Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. AB - Autoproteolysis of the retroviral aspartyl proteases is a major obstacle to purification and analysis of these enzymes. A mutagenic approach to rendering autolytic cleavage sites less labile was applied to the primary cleavage site between Leu5 and Trp6 in human immunodeficiency virus-1 (HIV-1) protease. From predictions based on known substrates it was concluded that amino acids Lys or Ser in place of Gln at position 7 would prevent cleavage at the Leu5-Trp6 peptide bond, therefore stabilizing the protein. Autoproteolytic stability was enhanced at least 100-fold by these mutations. At longer time points the protease was degraded at secondary sites which contained adequate substrate sequences but were conformationally restricted. Conversely, a mutation in HIV-2 protease which changed Lys7 to Gln rendered the protein 3-fold less stable and shifted the position of the initial autoproteolytic cleavage from Phe3-Ser4 to Leu5-Trp6. The effects of these mutations demonstrate that small changes in protein sequence can have a major impact on their autoproteolytic stability. The work described here suggests a general method for stabilizing proteases and perhaps other recombinantly produced proteins to autolysis. PMID- 8505319 TI - Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation. AB - We have determined whether macrophage derived-foam cells, a prominent component of the atherosclerotic lesion, express more urokinase-type plasminogen activator (uPA) and whether their ability to generate plasmin stimulates the release of matrix-bound growth factors. Steady state levels of uPA mRNA and both membrane and intracellular uPA activities were significantly increased in foam cells. When cultured on cell-derived matrices containing bound 125I-basic fibroblast growth factor (bFGF), both macrophage and foam cells released intact 125I-bFGF into their media. The release of 125I-bFGF by either cell was significantly enhanced in the presence of plasminogen. However, foam cells, which expressed more membrane uPA, released more 125I-bFGF than control cells. The release of matrix bound bFGF was independent of heparanase activity, since neither macrophage nor foam cells degraded 35SO4-labeled heparan sulfate proteoglycans. In addition, media derived from foam cells cultured on cell-derived matrices in the presence of plasminogen had increased levels of transforming growth factor (TGF) beta activity as compared to cells grown in the absence of plasminogen. In contrast, plasminogen had no effect on TGF-beta activity recovered in the media of foam cells grown on plastic. Moreover, when macrophage were cultured on matrices containing bound 125I-TGF-beta, the release of labeled TGF-beta was increased in the presence of plasminogen. This is the first demonstration that foam cells can release two important growth regulators, bFGF and TGF-beta, from the extracellular matrix, and provides a mechanism by which macrophage and foam cells can stimulate atherosclerotic lesion development. PMID- 8505320 TI - Staphylococcus aureus alpha-toxin. Production of functionally intact, site specifically modifiable protein by introduction of cysteine at positions 69, 130, and 186. AB - Staphylococcal alpha-toxin, the prototype of an oligomerizing, pore-forming cytotoxin, is sensitive to biochemical modifications and cannot be labeled with biotin or fluorescein under preservation of its biological activity. In this study, we have used site-directed mutagenesis to introduce cysteine residues at positions 69, 130, and 186. Each mutant was fully and rapidly reactive with several sulfhydryl-specific reagents, indicating superficial location. Coupling of SH-groups with fluorescein-maleimide or biotin-maleimide was tolerated without loss of hemolytic activity at position 130, and the formed hexamers were visible on target cells by fluorescence microscopy and could be detected on electroblots by reaction with streptavidin-peroxidase. At the two other positions, modification caused significant loss of activity. However, the labeled proteins still bound to red cells, as shown by fluorescence microscopy and electroblotting. Intrinsically labeled alpha-toxin represents a novel tool to study the interaction of this pore-former with target membranes. PMID- 8505321 TI - Altered pore-forming properties of proteolytically nicked staphylococcal alpha toxin. AB - Staphylococcal alpha-toxin is a single-chain polypeptide with a molecular weight of 34,000 that hexamerizes in lipid bilayers to form pores of 1-1.5 nm effective diameter in membranes. We demonstrate that limited proteolysis of purified alpha toxin with proteinase K generates a hemolytically active product that yields one major protein band of 17-18 kDa in SDS-polyacrylamide gel electrophoresis. The 17 18-kDa protein band harbors two major fragments of similar size representing the N- and C-terminal halves, which remain associated with each other in non denaturing buffers but dissociate in 6 M urea. Dissociation in urea leads to loss of hemolytic activity. In contrast, unnicked alpha-toxin is not inactivated by urea. Nicked, hemolytically active alpha-toxin forms hexamers on erythrocyte membranes and on lymphocytes and monocytes. However, the nicked toxin can only lyse erythrocytes and fails to permeabilize nucleated cells. Osmotic protection experiments indicate that the size of pores generated by the nicked toxin is considerably smaller (0.6-0.9 nm effective diameter) than that generated by native toxin. The collective results do not support a previous proposal that different functions of alpha-toxin are contained in separate domains of the molecule. PMID- 8505322 TI - Aluminum-induced nonenzymatic phospho-incorporation into human tau and other proteins. AB - Incubation of purified recombinant human tau protein with aluminum salts at concentrations > or = 100 microM induces aggregation of tau that prevents its entry into SDS-polyacrylamide gels and filtration through nylon membranes. This effect is noncovalent and can be reversed by addition of EDTA. However, when incubated along with ATP, GTP, or CTP, aluminum catalyzes a covalent linkage that results in incorporation of the alpha- and gamma-phosphates into the tau protein (phospho-incorporation). The sensitivity to phosphatases and partial hydrolysis and the labeling observed with ATP containing radioisotopes at different positions suggest a novel reaction in which the entire triphosphate moiety is transferred from ATP and linked to tau via an O-linkage to the alpha-phosphate. The aggregation and triphosphorylation phenomena were not catalyzed by divalent or quadrivalent cations, but similar effects were observed with some other trivalent cations. They occurred at aluminum concentrations similar to those found in human brains with Alzheimer's disease, suggesting the possibility that related reactions may have physiological significance in vivo. PMID- 8505323 TI - Human Hageman factor (factor XII) and high molecular weight kininogen compete for the same binding site on human umbilical vein endothelial cells. AB - Factor XII (FXII, plasma concentration 375 nM) is a critical member of the plasma contact activation system and is the zymogen form of FXIIa, a serine protease involved in intrinsic coagulation, complement activation, activation of factor VII, and generation of the vasoactive peptide bradykinin. As such its interaction with cells involved in inflammatory pathways can be of physiologic and pathologic significance. We have studied the binding of FXII to cultured human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with 125I-FXII, and cell bound factor FXII was measured. FXII bound to HUVEC saturably in a zinc-dependent manner. The optimal zinc concentration was 50-60 microM. Binding of labeled FXII was drastically reduced when a 200-fold molar excess of unlabeled FXII was included in the incubation mixture at time zero or when added at 60 min during a 150-min time course experiment. Quantitative binding experiments indicated a dissociation constant of 144 nM with 10-12 million binding sites/endothelial cell. Unlabeled high molecular weight kininogen (HK) inhibited the binding of labeled FXII with a Ki of 98 nM, whereas unlabeled FXII inhibited the binding of labeled HK to HUVEC with a Ki of 152 nM. SDS-polyacrylamide gel electrophoresis and autoradiography of cell-bound 125I-FXII showed that factor XII underwent limited proteolysis and the molecular weights of the fragments were similar in size to activated FXII. The cell-bound activated factor XII was also able to activate prekallikrein. These data suggest that (i) FXII binds to HUVEC specifically, saturably, and reversibly in a zinc-dependent manner, (ii) HK and FXII may compete with each other for the same cell-surface receptor/s, and (iii) cell-bound FXII is capable of undergoing activation to FXIIa. PMID- 8505324 TI - Comparison of the patterns of expression of rat intestinal fatty acid binding protein/human growth hormone fusion genes in cultured intestinal epithelial cell lines and in the gut epithelium of transgenic mice. AB - The intestinal fatty acid binding protein gene (Fabpi) provides a good model system for studying how gene transcription is regulated in enterocytes as a function of their differentiation program and location along the duodenal-to colonic axis. We have compared and contrasted the transcriptional activity of four fusion genes composed of elements from the 5'-nontranscribed domain of rat Fabpi linked to the human growth hormone gene (I-FABP/hGH) in transgenic mice and in five primate epithelial cell lines derived from intestine, liver, kidney, and cervix. Nucleotides -103 to +28 of rat Fabpi are able to direct appropriate lineage-specific and geographic patterns of hGH expression in transgenic mice. I FABP-103 to +28/hGH is preferentially expressed in Caco-2 cells, which emulate some of the features of differentiated small intestinal enterocytes after they reach confluence. However, other I-FABP/hGH fusion genes that exhibit differentiation-dependent changes in their expression along the crypt-to-villus axis do not manifest the same pattern of differentiation-dependent change in activity in this cell line. Correlation of their patterns of expression in vivo and ex vivo suggest that nonproliferating Caco-2 cells mimic some of the features of the transcriptional regulatory environment of enterocytes located in the upper crypt. Nucleotides -103 to +28 of rat Fabpi contain one copy of a repeated 14 base pair element that is conserved in the orthologous mouse and human genes and represented in several other homologous and nonhomologous genes, which are expressed in villus-associated enterocytes. This element binds to two members of the steroid hormone receptor superfamily of transcription factors produced in enterocytes and Caco-2 cells: hepatic nuclear factor-4 (HNF-4) and apolipoprotein regulatory protein-1 (ARP-1). Co-transfection studies performed in Caco-2 cells and in a monkey kidney cell line (CV-1) that lacks endogenous pools of ARP-1 and HNF-4 suggest that ARP-1 and HNF-4 can function to activate I-FABP-103 to +28/hGH+3 through their interactions with the 14-base pair element. This activation appears to be affected by elements located between nucleotides -277 and -104 and other transcription factors. PMID- 8505325 TI - Transactivation of the grp78 promoter by Ca2+ depletion. A comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. AB - The calcium ionophore A23187 has been shown to induce the expression of a set of glucose-regulated protein (GRP) genes through the depletion of Ca2+ from the intracellular Ca2+ stores. Here we demonstrate that thapsigargin, which inhibits specifically the endoplasmic reticulum Ca(2+)-ATPase and causes a discharge of the intracellular Ca2+ store, is able to induce the transcription of two grp genes (grp78/BiP and grp94) with kinetics and magnitude similar to that of A23187. The induction of the grp genes by both reagents requires several hours of sustained treatment, in contrast to the rapid induction previously described for c-jun and c-fos. The transactivation of the rat grp78 promoter by A23187 is mediated through sequences spanning -154 to -130 and -99 to -90. Further, simultaneous mutation of two 10-base pair regions, spanning -139 to -130 and -99 to -90, severely reduced the A23187 response. The induction by thapsigargin is also partially mediated through these same promoter elements, without the involvement of the TRE and CRE-like elements of the grp78 promoter. The Ca2+ response elements are further defined by their ability to confer Ca2+ stress inducibility to a heterologous promoter. We show that subdomains of the grp78 promoter are capable of conferring the Ca2+ stress response. In particular, two copies of a 50-base pair region spanning -159 to -110, when cloned in either orientation, can confer a 5- and 9-fold induction by A23187 and thapsigargin, respectively. Our results lend support to the hypothesis that the induction of grp78 by A23187 and thapsigargin following ER Ca2+ discharge acts through a novel pathway in which a Ca2+ signal is transduced through redundant elements containing CCAAT box-like motifs flanked by GC-rich regions. PMID- 8505326 TI - Uncleaved signals for glycosylphosphatidylinositol anchoring cause retention of precursor proteins in the endoplasmic reticulum. AB - Glycosylphosphatidylinositol (GPI)-anchored proteins are generally absent from the surface of cells that are defective in GPI biosynthesis. The current study was undertaken to: (a) examine in detail the intracellular localization and fate of precursors of GPI-anchored proteins in cells that fail to add GPI groups and (b) define structural characteristics of the precursor proteins that determine their intracellular localization. By examining GPI-deficient cells, we show that the uncleaved precursor of the GPI-anchored protein, Q7b, is retained in the cisternae of the endoplasmic reticulum (ER) and is largely lost intracellularly with a half-time of 2-4 h. Only a small amount (1-10%) of a proteolytically cleaved form of the protein is secreted into the medium. In cells competent for GPI anchor addition, mutation of the putative cleavage/attachment site for GPI addition in Q7b results in a similar phenotype of ER retention of the uncleaved precursor. An aspartic acid residue (Asp316) within the Q7b GPI anchoring signal, previously found to be essential for GPI anchor addition (Waneck, G. L., Stein, M. E., and Flavell, R. A. (1988) Science 241, 697-699), is also shown to be critical for ER retention. Information leading to ER retention is transferable to another protein leading to ER retention is transferable to another protein by fusion of the GPI anchoring signals from either Q7b or the GPI-anchored form of the IgG Fc receptor type III. Analysis by sedimentation on sucrose gradients shows that Q7b species retained in the ER are multimeric, whereas species that exit the ER are monomeric. This correlation suggests that the presence of an uncleaved signal for GPI anchoring induces changes in the aggregation state of the precursor proteins, which may lead to their retention in the ER. PMID- 8505327 TI - The contributions of individual gamma-carboxyglutamic acid residues in the calcium-dependent binding of recombinant human protein C to acidic phospholipid vesicles. AB - The dependence on the integrity of the human protein C (PC) gamma-carboxyglutamic acid (Gla) domain on its Ca(2+)-dependent binding properties to acidic phospholipid (PL) vesicles has been examined by analysis of these interactions with recombinant (r)-PC Gla domain muteins. The concentration of Ca2+ that results in 50% saturation (C50-Ca) of PL with wild-type (wt) r-PC was not altered by more than 2-fold for the following r-variants of PC, viz. [Gla6-->Asp]r-PC, [Gla14-->Asp]r-PC, [Gla19-->Asp]r-PC, [Gla25-->Asp]r-PC, [Gla29-->Asp]r-PC, and [Gln32-->Gla]r-PC. The C50-Ca was substantially higher than that of wtr-PC for [Gla7-->Asp]r-PC (8.2 mM), [Arg15-->Leu]r-PC (4.5 mM), [Gla16-->Asp]r-PC (> 10 mM), [Gla20-->Asp]r-PC (> 10 mM), and [Gla26-->Asp]r-PC (> 10 mM), indicating that the Ca(2+)-induced conformations of these latter variants interacted poorly with these acidic PL vesicles. Titration of the PL vesicles with wtr-PC at a constant concentration of 20 mM Ca2+ leads to calculation of a concentration of PC that results in 50% saturation of the PL (C50-PC) of 0.38 microM. Essentially this same value was determined for the r-mutants, [Gla7-->Asp]r-PC and [Gln32- >Gla]r-PC. An approximate 2-fold lower C50-PC was obtained for [Gla14-->Asp]r-PC (0.14 microM), [Gla25-->Asp]r-PC (0.16 microM), and [Gla29-->Asp]r-PC (0.15 microM). Somewhat higher C50-PC values were found for [Gla6-->Asp]r-PC (1.2 microM), [Arg15-->Leu]r-PC (1.2 microM), [Gla16-->Asp]r-PC (1.2 microM), [Gla19- >Asp]r-PC (1.8 microM), [Gla20-->Asp]r-PC (1.1 microM), and [Gla26-->Asp]r-PC (1.6 microM). The results of this investigation, in conjunction with other structural and functional studies with these mutants, and the x-ray crystallographic structure of the prothrombin Gla domain-Ca2+ complex, show that Gla16 and Gla26 are the most indispensable Gla residues for maintenance of the functional Ca(2+)-dependent structure of the Gla domain of PC, whereas Gla14 is the least critical Gla residue in this regard. Of the non-Gla residues investigated, Arg15 is of great importance for maintenance of a functional Ca(2+) dependent structure of PC, and insertion of a Gla residue at position 32, a situation that exists in the cases of some other proteins of this type, does not significantly alter these characteristics of r-PC. PMID- 8505328 TI - N-recognin/Ubc2 interactions in the N-end rule pathway. AB - The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, substrates of the N end rule pathway are targeted for degradation by a complex that includes the 225 kDa N-recognin, encoded by UBR1, and the 20-kDa ubiquitin-conjugating enzyme encoded by UBC2. We report that both physical stability and functional activity of the N-recognin.Ubc2 complex require the presence of a highly acidic 23-residue region at the C terminus of Ubc2. Ubc2-C88A, an inactive variant of Ubc2 in which the active-site Cys-88 has been replaced by Ala, is shown to retain the affinity for N-recognin. Expression of Ubc2-C88A inhibits the N-end rule pathway, apparently as a result of competition between Ubc2 and Ubc2-C88A for binding to N recognin. The two-hybrid (interaction cloning) technique was used to identify a approximately 170-residue C-terminal fragment of the 1,950-residue N-recognin as a Ubc2-interacting domain. We also show that the level of UBR1 mRNA decreases upon overexpression of UBC2. This effect of UBC2 is observed with cells whose UBR1 is expressed from an unrelated promoter but is not observed if UBR1 contains a frameshift mutation, or if the Ubc2 protein lacks its C-terminal acidic region. The N-recognin.Ubc2 complex appears to regulate the expression of N-recognin through changes in the metabolic stability of its mRNA. PMID- 8505329 TI - Purification, characterization, and cDNA cloning of an antifungal protein from the hemolymph of Sarcophaga peregrina (flesh fly) larvae. AB - An antifungal protein (AFP) was purified from the hemolymph of third instar larvae of Sarcophaga peregrina. This protein repressed the growth of Candida albicans in Sabouraud medium in the presence of nitrofurazone. However, in distilled water or saline, AFP alone killed C. albicans. Significant synergism was detected between AFP and sarcotoxin IA, an antibacterial protein of Sarcophaga. The lethal effect of AFP on C. albicans was greatly enhanced by the presence of a small amount of sarcotoxin IA. AFP was shown to bind to C. albicans and cause leakage of a substance(s) with absorbance at 260 nm from the cells. Analysis of its cDNA showed that AFP is a novel histidine-rich protein consisting of 67 amino acid residues. PMID- 8505330 TI - Structure/function analysis of the transmembrane domain of DAB389-interleukin-2, an interleukin-2 receptor-targeted fusion toxin. The amphipathic helical region of the transmembrane domain is essential for the efficient delivery of the catalytic domain to the cytosol of target cells. AB - Cassette and deletion mutagenesis were used to analyze the function of the amphipathic alpha-helices in the transmembrane domain of DAB389-interleukin-2 (IL 2), a fusion protein which is targeted to the interleukin-2 receptor. We demonstrate that the in-frame deletion of 60 amino acids, from Asn204 to Glu263 in DAB389-IL-2, results in complete loss of cytotoxic activity, whereas when the amphipathic regions from Asp208 to Ser220 and Ala244 to His258 are replaced with idealized amphipathic helices composed of repeating Glu, Lys, and Leu residues, the mutant fusion toxin has low but detectable activity. DAB389-IL-2 and both variants form channels in artificial phospholipid bilayers with conductances identical to those formed by diphtheria toxin. Both mutant fusion toxins bind to the high affinity IL-2 receptor with affinities similar to that of DAB389-IL-2. The fact that these mutants have markedly reduced or absent cytotoxic activity, but possess "wild type" catalytic activity, binding affinities, and channel conductances, suggests the existence of a step in the intoxication pathway, defective in the mutants, which occurs after DAB389-IL-2 binds to the IL-2 receptor. It is unknown whether this step occurs prior or subsequent to channel formation, but it is essential for the efficient delivery of the ADP ribosyltransferase from DAB389-IL-2 to the cytosol of target cells. PMID- 8505331 TI - Binding of coatomer to Golgi membranes requires ADP-ribosylation factor. AB - Coatomer, a complex of seven proteins, appears to be the precursor of the coat structure of non-clathrin-coated Golgi-derived vesicles. Another component of this vesicle coat is the cytosolic protein ADP-ribosylation factor (ARF). Like coatomer, ARF appears to reversibly associate with Golgi membranes. We now report that ARF is required for coatomer binding to Golgi membranes and that myristoylated, but not non-myristoylated, ARF is the required species. We utilize an antibody directed against the beta-subunit of coatomer (beta-COP) to follow coatomer binding. ARF and beta-COP bind stoichiometrically to Golgi membranes. ARF-dependent beta-COP binding requires a membrane-associated protein, is saturable, and is enhanced in the presence of stable GTP analogues like guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). ARF and beta-COP bind sequentially to Golgi membranes, since beta-COP can be bound to reisolated membranes that had been previously incubated with ARF and GTP gamma S. We conclude that membrane bound ARF confers to Golgi membranes all of the requirements for specific beta COP binding. PMID- 8505332 TI - The human mRNA encoding the Goodpasture antigen is alternatively spliced. AB - The noncollagenous (NC1) domain of the human collagen alpha 3(IV)-chain is the primary target of autoantibodies produced in Goodpasture syndrome and, therefore, has been designated as the Goodpasture antigen. In this report, we show that Goodpasture antigen mRNA undergoes processing to at least two alternatively spliced forms in a variety of human tissues, resulting in the exclusion of sequence encoded by either one or two exons. Interestingly, no alternatively spliced forms were observed in bovine or rat tissues. The derived amino acid sequences of the two variant mRNA forms are identical and significantly shorter than that arising from the complete Goodpasture antigen mRNA. They lack the carboxyl-terminal region contributing to the formation of the Goodpasture epitope and all but one of the cysteines found in the complete form. These sequence characteristics suggest that, if translated, the variant Goodpasture antigen is likely to be defective in triple helix formation and no longer reactive with Goodpasture autoantibodies. Although each tissue expressing Goodpasture antigen displayed a specific mRNA pattern, the complete form was always the most abundant and was present at levels apparently unrelated to whether or not the organ of origin is a potential target in Goodpasture syndrome. Furthermore, the antigen sequence was identical in the kidneys of normal and Goodpasture-affected individuals, and no major differences in the expression of the complete and spliced forms were observed. PMID- 8505333 TI - Glycoprotein biosynthesis in the alg3 Saccharomyces cerevisiae mutant. I. Role of glucose in the initial glycosylation of invertase in the endoplasmic reticulum. AB - Oligosaccharides on invertase restricted to the endoplasmic reticulum (ER) in alg3,sec18 yeast at 37 degrees C were found to be 20% wild type Man8GlcNAc and 80% Man1 alpha-->2Man1 alpha-->2Man1 alpha-->3(Man1 alpha-->6)Man1 beta- >4GlcNAc2 (Verostek, M.F., Atkinson, P.H., and Trimble, R. B. (1991) J. Biol. Chem. 266, 5547-5551). These results suggested that alg3 was slightly leaky, but did not address whether the oligosaccharide-lipid Man9GlcNAc2 and Man5GlcNAc2 precursors were glucosylated in alg3 yeast. Therefore, an alg3,sec18,gls1 strain was constructed to delete the GLS1-encoded glucosidase I responsible for trimming the terminal alpha 1,2-linked glucose from newly transferred Glc3ManxGlcNAc2 oligosaccharides. Invertase activity was overexpressed 5-10-fold on transforming this strain with a multicopy plasmid (pRB58) carrying the SUC2 gene, and preparative amounts of the ER form of external invertase, derepressed and accumulated at 37 degrees C, were purified. The N-linked glycans were released by sequential treatment with endo-beta-N-acetylglucosaminidase H (endo H) and peptide-N4-N-acetyl-beta-glucosaminyl asparagine amidase. Oligosaccharide pools were sized separately on Bio-Gel P-4, which showed that endo H released about 17% of the carbohydrate as Glc3Man8GlcNAc, while peptide-N4-N-acetyl-beta glucosaminyl asparagine amidase released the remainder as Hex8GlcNAc2 and Man5GlcNAc2 in a 1:4 ratio. Glycan structures were assigned by 500-MHz two dimensional DQF-COSY 1H NMR spectroscopy, which revealed that the endo H resistant Hex8GlcNAc2 pool contained Glc3Man5GlcNAc2 and Man8GlcNAc2 in a 6:4 ratio, the latter a different isomer from that formed by the ER alpha 1,2 mannosidase (Byrd, J. C., Tarentino, A. L., Maley, F., Atkinson, P. H., and Trimble, R. B. (1982) J. Biol. Chem. 257, 14657-14666). Recovery of Glc3Man8GlcNAc and not the ER form of Man8GlcNAc provided an internal control indicating the absence of glucosidase I, which was confirmed by incubation of [3H]Glc3[14C]Man9GlcNAc with solubilized membranes from either alg3,sec18,gls1 or alg3,sec18,GLS1 strains. Chromatographic analysis of the products showed that [3H]Glc was removed only in the presence of the GLS1 gene product. Thus, the vast majority of the N-linked glycosylation in the ER of alg3 yeast (> 75%) occurs by transfer of Man5GlcNAc2 without prior addition of the 3 glucoses normally found on the lipid-linked precursor. PMID- 8505334 TI - Glycoprotein biosynthesis in the alg3 Saccharomyces cerevisiae mutant. II. Structure of novel Man6-10GlcNAc2 processing intermediates on secreted invertase. AB - Alg3 yeast mutants synthesize endoglycosidase H-resistant oligosaccharides whose precursor for elongation is Man1 alpha-->2Man1 alpha-->2Man1 alpha-->3(Man1 alpha ->6)Man1 beta-->4GlcNAc2 (Verostek, M.F., Atkinson, P.H., and Trimble, R. B. (1991) J. Biol. Chem. 266, 5547-5551). To characterize alg3 glycan elongation in vivo, oligosaccharides on alg3,sec18 invertase synthesized and secreted at 26 degrees C were released with peptide-N4-N-acetyl-beta-glucosaminyl asparagine amidase and purified by Bio-Gel P-4 chromatography. Large (Man > 30GlcNAc2) and intermediate (Man5-10GlcNAc2) sized oligosaccharides were pooled separately, and the smaller ones were exchanged with 2H2O for one- and two-dimensional DQF-COSY 1H NMR analyses at 500 MHz. Although there was no detectable substitution of the terminal alpha 1,6-core-linked mannose, addition of alpha 1,6-, alpha 1,2-, and alpha 1,3-mannoses to the alpha 1,3-linked core branch of a majority of the Man5 precursor was analogous to core-filling reactions seen on wild type invertase glycans (Trimble, R.B., and Atkinson, P.H. (1986) J. Biol. Chem. 261, 9815-9824). Two additional types of oligosaccharide structures were found; those which retained glucose and those consistent with mannan elongation. Glucose retention appeared to be due to inefficient trimming from minor glucosylated intermediates, while mannan elongation was by extension of a new alpha 1,6-linked branch from the alpha 1,3-core-linked residue as seen in wild-type core oligosaccharides (Hernandez, L.M., Ballou, L., Alvarado, E., Gillece-Castro, B.L., Burlingame, A.L., and Ballou, C. E. (1989) J. Biol. Chem. 264, 11849-11856) or mnn1,mnn2,mnn10 processing intermediates (Ballou, L., Alvarado, E., Tsai, P-k., Dell, A., and Ballou, C.E. (1989) J. Biol. Chem. 264, 11857-11864). Thus, the alpha 1,6-linked branch additions which form Man9GlcNAc2-PP-dolichol from Man5GlcNAc2-PP-dolichol appear to provide important structural information enabling efficient recognition by the endoplasmic reticulum-glucosyltransferases forming oligosaccharide-lipid as well as the glucosidases involved in early trimming reactions, but the alg3 mutant documents that they are unnecessary for normal yeast mannan elongation. PMID- 8505335 TI - Sodium dodecyl sulfate-induced dissociation of complexes between human tissue plasminogen activator and its specific inhibitor. AB - The stability of complexes between serine proteinases and their inhibitors after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis has been claimed to indicate covalent bond formation. In this work we have investigated the effects of SDS on the stability of complexes between single-chain or two-chain tissue plasminogen activator (t-PA) and its inhibitor (PAI-1). Complexes formed by incubation of t-PA with PAI-1 for 15 min at 22 degrees C were further incubated with various amounts of SDS before being subjected to SDS polyacrylamide gel electrophoresis. The molecular species in the gels were identified both by zymography or by autoradiography after immunoblotting with antibodies directed against either t-PA or PAI-1. It was demonstrated that the interaction of SDS with t-PA.PAI-1 complexes before electrophoresis resulted in a transition from the complexed state to the free forms of t-PA and PAI-1 in a time and dose-dependent manner. The first-order dissociation rate constant in the presence of 35 mM SDS at 22 degrees C had a koff value of 1.4 x 10(-2) min-1, which corresponds to a half-life of 49.5 min. The t-PA released from the complexes was fibrinolytically active, whereas the released PAI-1 inhibited activator-dependent fibrinolysis. In a similar fashion, the well characterized nonacylated pair alpha 1-proteinase inhibitor-elastase was dissociated by SDS treatment, confirming the validity of our experimental approach to demonstrate the reversibility of t-PA.PAI-1 complexes. These results demonstrate that SDS polyacrylamide gel electrophoresis traps the molecular species in the state in which the proteins existed prior to the analysis, and they suggest that under the conditions used, the interaction of t-PA with PAI-1 results in the formation of nonacylated reversible complexes. This phenomenon may be relevant to the pathophysiology of fibrinolysis and to the general mechanism of serine proteinase inhibitor complex formation. PMID- 8505336 TI - Mitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production. AB - The expression of nuclear and mitochondrial oxidative phosphorylation (OXPHOS) genes was examined in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), myoclonic epilepsy associated with ragged red fibers (MERRF), and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and compared with controls. In KSS muscle, mtDNA transcripts outside the deletion were elevated, while those within the deletion were reduced according to the percentage of deleted mtDNA molecules. In MERRF and MELAS muscle, mitochondrial transcripts levels were increased, but the increase was greater in MERRF muscle. The processing of mtDNA transcripts was reduced in all pathogenic muscles. This was true for full-length heavy and light strand transcripts as well as for the 16 S rRNA + tRNA(Leu)+ND1 transcript. However, the tRNA(Lys) level was reduced in all three muscles. In MELAS muscle, our results are not consistent with an impairment of transcription termination at the end of the 16 S mitochondrial rRNA. Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle. The results demonstrate that the expression of nuclear and cytoplasmic OXPHOS genes is coordinated and that OXPHOS gene expression increases to compensate for respiratory deficiency. The repression of nuclear genes in KSS muscle could be a consequence of the segmental distribution of deleted mtDNA molecules in muscle cells. PMID- 8505337 TI - Type XIV collagen is encoded by alternative transcripts with distinct 5' regions and is a multidomain protein with homologies to von Willebrand's factor, fibronectin, and other matrix proteins. AB - The combined nucleotide sequences of several overlapping cDNAs provide the first complete amino acid sequence of type XIV collagen. Independent confirmation of the deduced sequence is provided by amino acid sequencing of several tryptic peptides isolated from purified chicken skin type XIV collagen. Comparative analyses show that the amino-terminal non-triple-helical region of alpha 1(XIV) chains contains sequence motifs that are similar to alpha 1(IX) collagen, fibronectin type III repeats, and von Willebrand's factor A-domains. The results also strongly suggest that the alpha 1(XIV) collagen gene is identical to the gene encoding the matrix component previously named undulin. cDNAs covering the 5' region of alpha 1(XIV) mRNA fall into two classes with distinct sequences in their 5'-untranslated regions. We believe the two alternative sequences result from differential splicing of the primary transcript. Interestingly, one of the untranslated sequences shows a high degree of identity with the cis-regulatory translational control sequence in the 5'-untranslated region of a Drosophila ribosomal protein mRNA. We hypothesize therefore that the sequence in alpha 1(XIV) collagen may play a role in the control of alpha 1(XIV) protein synthesis. PMID- 8505338 TI - Analysis of structure-function relationships in the platelet membrane glycoprotein Ib-binding domain of von Willebrand's factor by expression of deletion mutants. AB - We have used a series of Escherichia coli-expressed deletion mutants of the glycoprotein (GP) Ib-binding domain of von Willebrand factor (vWF) to study the structural basis of its function. In addition to the prototypic molecule (rvWF441 733), we constructed 11 mutants; seven had deletions of sequence on the amino- and/or carboxyl-terminal side of the Cys509-Cys695 intrachain disulfide loop, and four had limited deletions inside the loop. Other cysteine residues in addition to 509 and 695, when present in the corresponding native sequence, were mutated to glycine; all molecules were purified in the oxidized as well as reduced and alkylated state. The smallest species retaining the ability to interact with GP Ib in the absence of modulators was the oxidized rvWF508-696; the latter, as well as rvWF441-696, became inactive after reduction and alkylation. In contrast, all the other fragments with deletions outside of the loop, but extending at least to residue 700, showed better binding to platelets after reduction and alkylation than when the Cys509-Cys695 disulfide bond was oxidized. Any limited deletion of sequence inside the loop caused complete loss of GP Ib-binding function both in the absence or in the presence of botrocetin, and this persisted even after reduction and alkylation. In contrast, all mutants with intact sequence between residues 509 and 695 bound to GP Ib in the presence of botrocetin, regardless of whether the 2 cysteine residues were oxidized or reduced and alkylated. Ristocetin, unlike botrocetin, appeared to have no effect in modulating the binding of any of the expressed fragments to platelets. Our findings suggest that the GP Ib-binding domain of vWF contains multiple interaction sites, but integrity of the sequence 509-695 is important for function. PMID- 8505339 TI - The role of glycosylation and phosphorylation in the expression of active human beta-glucuronidase. AB - Phosphorylation of mannose residues on N-linked oligosaccharide side chains of lysosomal enzymes targets them to lysosomes. We used site-directed mutagenesis to observe the effect of eliminating selective glycosylation sites from human beta glucuronidase on enzyme sorting. Expression studies allowed us to determine which of four potential sites were glycosylated, preferentially phosphorylated, and required for catalytic activity. All four sites of the human enzyme were glycosylated, whereas in the mouse and rat enzymes, only three of four sites are used. Sites 2 and 3 were preferentially phosphorylated. Elimination of sites 2 and 3 in combination markedly decreased sorting to lysosomes and increased enzyme secretion. Each of the four glycosylation sites could be eliminated individually without drastic reduction in catalytic activity. Activity was progressively lost as combinations of two, three, and four sites were eliminated. Wild-type enzyme produced in the presence of tunicamycin was also inactive, indicating that glycosylation is required for realization of enzyme activity. However, active enzyme could be deglycosylated with only minimal loss of activity. Mutant enzyme completely lacking glycosylation did not form tetramers. Partial restoration of tetramerization was achieved by the co-expression of normal rat enzyme, provided that the normal rat enzyme supplied at least two subunits to the tetramer. PMID- 8505340 TI - Characterization and hormonal regulation of the promoter of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Identification of functional and protein-binding regions. AB - Prostaglandin endoperoxide synthase isoform 2 (PGS-2) mRNA and protein are transiently induced by gonadotropins in granulosa cells of preovulatory follicles prior to ovulation. To better understand the hormonal regulation of the rat PGS-2 (rPGS-2) gene in these cells, genomic clones containing rPGS-2 as well as up to 6 kilobases of 5'-flanking DNA were isolated by screening a rat liver genomic library with a labeled 5'-fragment of the mouse PGS-2 cDNA. Primer extension analysis using ovarian follicular mRNA identified the presence of a single rPGS-2 transcription initiation site located 144 nucleotides upstream of the ATG translation initiation codon. To test for promoter activity within the 5' flanking region of the rPGS-2 gene, a genomic fragment, -2698/32 (1 = cap site), as well as a series of 5'-deletion mutants, were fused upstream of the chloramphenicol acetyltransferase (CAT) reporter gene and transfected into primary cultures of granulosa cells. Forskolin (7.5 microM), follicle-stimulating hormone (500 ng/ml) and luteinizing hormone (500 ng/ml) induced CAT activity following transfection with the -2698/32PGS.CAT, whereas gonadotropin-releasing hormone (10(-6) M) and interleukin-1 beta (30 ng/ml) had no effect. Deletion mutants delineated the region spanning from -192 to -54 of the transcription start site to be essential for both basal and forskolin-regulated expression of the reporter gene. The same DNA fragment (-192/-54) exhibited specific binding to granulosa cell nuclear extract proteins as analyzed by electrophoretic mobility shift assays. Additional specific bands were observed in extracts prepared from granulosa cells exposed to an ovulatory dose of gonadotropin. Collectively, these results provide the first structural and functional evidence that the transcriptional regulation of the rat PGS-2 gene by gonadotropins and forskolin in granulosa cells involves 5'-flanking DNA sequences, specifically a region between -192 and -54 of the transcription initiation site. PMID- 8505341 TI - A mouse Y box protein, MSY1, is associated with paternal mRNA in spermatocytes. AB - We have isolated a mouse cDNA clone, which encodes the protein MSY1 (mouse Y box protein 1), a new member of the Y box family of proteins. Northern analysis indicates that MSY1 mRNA accumulates over 100-fold more in testis than in other tissues. Moreover, MSY1 mRNA is developmentally regulated, initially appearing at the pachytene stage of spermatogenesis. This is the stage of maximal transcription and translation in the spermatocyte. In Xenopus laevis, homologous Y box proteins, FRGY1 and FRGY2, positively regulate transcription from promoters containing a Y box (CTGATTGGCCAA). In addition, the germ cell-specific Y box protein FRGY2 binds maternal mRNA within 60-80 S mRNP storage particles and in doing so regulates translation in the developing oocyte and embryo (Smith, L. D., Richter, J. D., and Taylor, M. A. (1984) in Molecular Biology of Development (Davidson, E. R., and Firtel, R. A., eds) pp. 129-141, Alan R. Liss, New York). The MSY1 protein can be isolated from a 60-80 S mRNP fraction of testis which like the frog oocyte contains stored, untranslated mRNAs. Furthermore, cross linking experiments demonstrate that MSY1 is bound to mRNAs of this fraction. Finally, mobility shift analysis performed using the isolated protein indicates that MSY1 has nucleic acid binding properties similar to those of the FRGY proteins. These data suggest that the mouse Y box protein, MSY1, functions similarly to the FRGY2 protein in regulating the storage and translation of germ cell RNAs. PMID- 8505342 TI - cDNA cloning and expression of the alpha and beta subunits of rat Rab geranylgeranyl transferase. AB - Rab geranylgeranyl transferase (Rab GG transferase) attaches 20-carbon geranylgeranyl groups to cysteine residues in Rab proteins that contain the COOH terminal sequence Cys-X-Cys or Cys-Cys. Rab GG transferase consists of two components that are separable in high salt solutions. Component A is a 95-kDa protein, and Component B is a heterodimer consisting of a 60-kDa alpha subunit and a 38-kDa beta subunit. In the current paper, we have cloned cDNAs for the alpha and beta subunits of Component B. The cDNAs for the rat alpha and beta subunits predict proteins of 567 and 331 amino acids, respectively. The mRNAs for both subunits are expressed in many tissues. When transfected together in embryonic kidney 293 cells, the alpha and beta subunit cDNAs produced Rab GG transferase activity that was stimulated in vitro by the addition of purified Component A. Comparisons of the amino acid sequences suggest that the proteins encoded by the Saccharomyces cerevisiae genes MAD2 and BET2 are the yeast counterparts of the mammalian Rab GG transferase alpha and beta subunits, respectively. PMID- 8505343 TI - Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. PMID- 8505344 TI - RNA polymerase II subunit RPB10 is essential for yeast cell viability. PMID- 8505345 TI - Optimization of structure and movement of the legs of animals. AB - The legs of animals, and their movements, have presumably been optimized by evolution and/or learning for the functions required of them in life. This paper presents a series of studies in which attempts have been made to formulate optimization problems, to which the legs and their movements may be solutions. These are studies of the ratio of radius to wall thickness in tubular bones; of the strengths of bones; of tendon thickness; of the gaits of turtles and of mammals; and of the technique of human high jumping. They illustrate some serious difficulties that may arise in inverse optimization studies but also show that the approach is helping to improve our understanding of legs and gaits. PMID- 8505346 TI - Muscle coordination of movement: a perspective. AB - Multijoint movement requires the coordination of many muscles. Because multijoint movement is complex, kinesiological data must be analyzed and interpreted in the context of forward dynamical models rich enough to study coordination; otherwise, principles will remain elusive. The complexity arises because a muscle acts to accelerate all joints and segments, even joints it does not span and segments to which it does not attach. A biarticular muscle can even act to accelerate one of the joints it spans opposite to its anatomical classification. For example, gastrocnemius may act to accelerate the knee into extension during upright standing. One powerful forward dynamical modeling method to study muscle coordination is optimal control theory because simulations of movement can be produced. These simulations can either attempt to replicate experimental data, without hypothesizing the purpose of the motor task, or otherwise generate muscle and movement trajectories that best accomplish the hypothesized task. Application of the theory to the study of maximum-height jumping has provided insight into the biomechanical principles of jumping, such as: (i) jump height is more sensitive to muscle strength than to muscle speed, and insensitive to musculotendon compliance; (ii) uniarticular muscles generate the propulsive energy and biarticular muscles fine-tune the coordination; and (iii) countermovement is often desirable, even in squat jumps, because it seems both to prolong the duration of upwards propulsion, and to give muscles time to develop force so the body can move upwards initially with high acceleration. The effort necessary to develop forward dynamical models has been so high, however, that model-generated data of jumping or any other task are meager. An interactive computer workstation environment is proposed whereby users can develop neuromusculoskeletal control models, generate simulations of motor tasks, and display both kinesiological and modeling data more easily (e.g., animations). By studying a variety of motor tasks well, each within a theoretical framework, hopefully muscle coordination principles will soon emerge. PMID- 8505347 TI - Sequential motions of body segments in striking and throwing skills: descriptions and explanations. AB - The motions of segments participating in striking and throwing skills are generally sequenced in a proximal-to-distal fashion. These sequences are often described in terms of the linear velocities of the segment endpoints, joint angular velocities or segment angular velocities. While each method of description has its own merit, the latter is recommended since it leads to an intuitively pleasing way of explaining segment motions. Explanations of segment motion sequences are dependent not only on a knowledge of the joint moments driving the system of linked segments, but on the way the segments interact as functions of their motions and orientations. The motion-dependent interaction among segments is significant and offers an explanation of the sequencing of segment motions. As illustrated by the thigh and lower leg in kicking and by the upper arm and forearm in overarm pitching, the forward acceleration of the proximal segment plays a large role in causing the distal segment to lag behind. The subsequent forward acceleration of the distal segment is largely a result of the way the proximal segment interacts with the distal segment as a function of the proximal segment's angular velocity. The proximal segment is subsequently slowed down largely due to the motion-dependent effect of the distal segment on the proximal segment. Differences in the way segments interact in striking and throwing skills can account for variations in the timing of segment actions and these differences need to be examined before establishing general principles governing striking and throwing. PMID- 8505348 TI - A biomechanical analysis of muscle strength as a limiting factor in standing posture. AB - We developed a method for studying muscular coordination and strength in multijoint movements and have applied it to standing posture. The method is based on a musculoskeletal model of the human lower extremity in the sagittal plane and a technique to visualize, geometrically, how constraints internal and external to the body affect movement. We developed an algorithm to calculate the set of all feasible accelerations (i.e., the 'feasible acceleration set', or FAS) that muscles can induce. For the ankle, knee, and hip joints in the sagittal plane, this set is a polyhedron in three dimensions. Using the volume of the FAS as an indicator of overall mobility, we found that strengthening muscles on the posterior side (as opposed to the anterior) of the body would cause greater increases in mobility. Employing the experimental observations of others, we also found that acceleration constraints greatly reduce the range of feasible accelerations. We then defined a set of four basic acceleration vectors which, when used in various combinations, can produce the repertoire of postural movements. We used linear programming to find the maximum magnitudes of these vectors, and the sensitivity of these magnitudes to muscle strength, thereby delineating those muscles which, if strengthened, would cause the greatest increase in the body's ability to generate the basic acceleration vectors. For our particular model, those muscle groups were found to be hamstrings, tibialis anterior, rectus femoris, and gastrocnemius. These muscle groups would be of great importance in cases involving severely reduced muscle strength. This methodology may therefore be useful for purposes such as design of functional electrical stimulation controllers or exercises for persons at risk for falling. PMID- 8505349 TI - Evaluation of methods to minimize cross talk in surface electromyography. AB - The purposes of this study were to quantify the effectiveness of various methods to minimize cross talk in surface electromyography (EMG) using common recording equipment, and to compare the intra- and interday variabilities of signals recorded with these methods. Comparisons were made for signals recorded with the single differential (SD), double differential (DD) and branched electrode (BE) techniques with large and small electrodes and corresponding interelectrode distances. The amount of cross talk in tibialis anterior EMG signals during maximum voluntary effort (MVE) triceps surae excitation was estimated using a protocol involving electrical stimulation of the triceps surae via the tibial nerve. In SD signals, cross talk averaged 12.2 and 10.2 percent MVE, for the large and small interelectrode distances, respectively. DD and BE signals contained significantly less cross talk (approximately 5 percent MVE for both techniques and interelectrode distances) than SD signals. The intra- and interday variabilities associated with these methods were estimated by recording tibialis anterior EMG signals during maximum voluntary isometric dorsiflexion (3 trials on each of 2 days) and calculating coefficients of variation for average-rectified values and median frequencies. EMG signals recorded with the small interelectrode distance showed greater interday amplitude variability than those recorded with the large interelectrode distance. Intra- and interday amplitude variabilities were similar across SD, DD and BE recording techniques. Intra- and interday frequency variabilities were similar across all experimental conditions. Thus, the DD and BE techniques, in conjunction with the large interelectrode distance (and large electrodes), provide a signal which contains significantly less cross talk than the SD technique without sacrificing intra- and interday amplitude and frequency stability. PMID- 8505350 TI - Ulceration, unsteadiness, and uncertainty: the biomechanical consequences of diabetes mellitus. AB - Diabetes mellitus, which results from a failure of the endocrine system to control blood glucose levels within normal limits, affects approximately 15% of the population over the age of 65 in developed countries. Between 20-50% of people with diabetes for more than 10 years will experience symmetrical distal sensory neuropathy resulting in a progressive, distal to proximal, loss of sensation in the lower extremities. The most common consequence is plantar ulceration that too often results in partial or total amputation of the foot. While neuropathy is a major permissive factor, plantar ulcers occur at locations of high plantar pressures. The measurement of pressure using tools developed and refined in the field of biomechanics has been shown to be a valuable asset to the management of the foot at risk for ulceration. In particular, the use of in-shoe measuring techniques has the potential to revolutionize the prescription of therapeutic footwear. Biomechanical techniques have also helped to evaluate other consequences of diabetic neuropathy on the foot such as callus formation, foot deformity, limited joint mobility and bony abnormalities. The reduction of afferent information from the lower extremities implies a lack of active feedback thought to be necessary for the control of human movements such as posture and gait. Our results show that diabetic neuropathy results in a significant increase in sway during standing that is not compensated for by other sensory systems. The study of the sagittal plane movements of the same individuals walking on a treadmill showed little effect on the kinematic control of gait when compared to age matched nonneuropathic control groups. This may indicate the dominance of efferent input over afferent feedback during gait. We believe that the study of the biomechanical consequences of diabetes can act as a model for many other diseases that have yet to come under the scrutiny of a multidisciplinary team. PMID- 8505351 TI - The energetics of running and running shoes. AB - It has been suggested that elastic energy storage and recovery in the cushioning system of an athletic shoe ('energy return') is a desirable quality that can enhance performance. However, comparing the energetics of a running shoe cushioning system with other passive energy exchange mechanisms in the running athlete suggests that the potential benefits of energy return are limited. The energetics of running shoe cushioning systems have been studied using a multiple element, non-linear viscoelastic model to analyse the effect on the shoe of plantar pressure distributions recorded in vivo. The running shoe is a net dissipator of energy but small quantities of strain energy, of the order of 10J, are stored and recovered during a running step. The actual energy exchanges depend on the cushioning material properties and the runner's plantar pressure distribution. Energy storage and recovery occurs throughout the step in different regions of the shoe midsole. Energy dissipation is confined almost entirely, both spatially and temporally, to the impact phase of ground contact. Thus the proportion of input energy recovered from the shoe is higher than that predicted by mechanical tests which stimulate only the impact phase of the step. Energy storage and recovery in the model shoe are large enough to have local effects on the energetics of the foot and lower leg but modest when compared with passive energy transfer within and between body segments or strain energy storage and recovery in the lower limb. Similarly, differences in the energy dissipated by well-designed shoes are predicted to be small and unlikely to have a direct effect on the energetics of the body as a whole. The possibility of indirect, kinematically mediated effects remains open, however. PMID- 8505352 TI - Computer simulation in sport and industry. AB - The last several decades have brought decreases in the specific cost of computer memory and increases in processor throughput. As a result simulation has become correspondingly more important as a component of industrial design and as a method for the study of general biomechanics and sports techniques. This paper illustrates, by way of examples, several of the more important aspects of the application of computer simulation to dynamic problems. Topics include (1) the ideas of suitable model complexity and its tradeoff with interpretability; (2) the sequential and iterative nature of model building and the importance of experimental data in the modelling and validation process; (3) the essential role of user-friendly software and graphical interfaces in the interchange of information between simulation programs and the users; and 4) the role of computer simulation in learning feedback loops, both in the field and in the computer laboratory. Most industrial use of simulation is in the design process. A similar approach is equally valid in biomechanics and sport applications through the incorporation of design variables, which may be easily changed in the model experiment. PMID- 8505353 TI - Bone and bones, architecture and stress, fossils and osteoporosis. AB - The combined use of architectural and stress technologies in osteological studies is starting to provide the basic biomechanical underpinnings to both evolutionary and applied medical investigations of bone. The architectural investigations, though tested using invasive methods, are aimed at non-invasive ways of obtaining information from radiographs of bones, fossils and people. They include optical (Fourier) data analysis (ODA) and computational Fourier transformations (FFT). The stress studies, though initially involving older techniques such as photoelastic stress analysis, now employ finite element analysis (FEA) and, most recently, fast Lagrangian analysis of continua (FLAC). Taken together, these methods are capable of providing more detailed knowledge of bone form and function that is important (a) in revealing functional adaptation in evolutionary studies of fossils and (b) for making early diagnosis and understanding pathological fractures in the late stages of osteoporosis. PMID- 8505354 TI - Citius, altius, longius (faster, higher, longer): the biomechanics of jumping for distance. AB - The purpose of this paper is to review current knowledge concerning the long and triple jumps. Much has been learned over the past two decades about techniques in the long jump. Many myths have been dispelled and many training practices have been altered as a result. In all of this, the techniques employed during the takeoff have received little attention. It is in this area that the most important developments are likely to take place in the next decade. In contrast with the long jump, satisfactory answers have yet to be obtained to even the most fundamental of questions about techniques in the triple jump. The triple jump is an experimental task with potential for use in studies of human locomotion, of visual perception and control, of the strength of biological materials and of the mechanisms of soft tissue injury. PMID- 8505355 TI - Human morphology: its role in the mechanics of movement. AB - Growth across the lifespan of males and females produces change in the form and structure of the human body which must be recognized in biomechanical models. The different morphologies for age span, gender and racial groupings have been identified and quantified by anthropometrists working primarily with measuring sticks and tapes. These parameters are not the parameters used to solve the dynamics problems of human movement. Models of the body composed of joints and rigid links have been formed and the inertial properties of the segments are required. The research which has been conducted to estimate these segment inertias is incomplete, dispersed, often flawed and inconclusive. However, it is essential that we have a reasonable understanding of the differences in inertia between individuals and changes of inertia within the individual regardless of age, sex and race. Segment inertia parameters can provide valuable insight into growth and the differences between individuals and populations. Segment morphology ranges from embryonic to excessive and each stage of growth or development has potential for the investigation of relationships between shape, size, inertia, weight and movement. The purpose of this paper is to examine research into segment inertias which provides useful information about the differences and changes to be expected. Although some guidance is provided, particularly with respect to bench mark studies, the paper is not intended as a discussion of methodologies. The studies which are pertinent to changes and differences in inertia make it clear that there are many interesting differences between age spans and, within these, differences between males and females and between races. If, in place of the expediency of proportions, segment parameters were measured and integrated into all studies, we would have a more complete representation of morphological changes and differences. PMID- 8505356 TI - Neuromuscular adaptations during the acquisition of muscle strength, power and motor tasks. AB - Neuromuscular performance is determined not only by the size of the involved muscles, but also by the ability of the nervous system to appropriately activate the muscles. Adaptive changes in the nervous system in response to training are referred to as neural adaptation. This article briefly reviews current evidence regarding the neural adaptations during the acquisition of muscle strength power and motor tasks and will be organized under four main topics, namely: (i) muscle strength gain: neural factors versus hypertrophy, (ii) neural adaptations during power training, (iii) neuromuscular adaptations during the acquisition of a motor task, and (iv) neuromuscular adaptations during a ballistic movement. PMID- 8505357 TI - A fresh look at the somatic cell genetics of hepatoma differentiation. PMID- 8505358 TI - Nuclear proteins of the bovine esophageal epithelium. I. Monoclonal antibody W2 specifically reacts with condensed nuclei of differentiated superficial cells. AB - Cells from three layers of the bovine esophageal epithelium, representing different stages of differentiation, were dissociated and separated by Percoll gradient centrifugation into fractions of small, medium and large sizes. A majority of the large cells possessed condensed nuclei, a characteristic feature of terminal differentiation of the superficial epithelium. The small cells resembled the proliferate cells of the basal layer. In vitro culture of the esophageal epithelial cells resulted in proliferation of the small cells, colony formation, and, in some cases, differentiation into cells with condensed nuclei. Nuclei, or nuclear subfractions derived from cells of the different layers, were used as immunogens for the generation of hybridomas secreting monoclonal antibodies that bound specifically to different regions of the esophageal tissue. One such antibody, designated W2, labeled the condensed nuclei from the superficial layer of stratified esophageal and corneal epithelia in situ, as well as the large cells from esophageal culture in vitro. Thus, the expression of the W2 antigen may be associated with the process of nuclear condensation during epithelial differentiation. Immunoisolation of the target antigen of W2 from extracts of large cells of the bovine esophagus yielded a band of M(r) approximately 33,000 on nonreducing polyacrylamide gels. This band dissociated into two polypeptides, of M(r) approximately 22,000 and approximately 11,000, upon treatment with dithiothreitol. Amino acid sequence analysis of the larger polypeptide showed extensive homology to a group of small calcium-binding proteins, including two helix-turn-helix motifs designated as the EF-hand, characteristic of the configuration of the metal-ion coordinating ligands of the calcium-binding site. Similarly, the sequence at the amino terminus of the polypeptide of approximately 11,000 indicated that it was the light chain counterpart of the same calcium-binding protein complex. PMID- 8505359 TI - Nuclear proteins of the bovine esophageal epithelium. II. The NuMA gene gives rise to multiple mRNAs and gene products reactive with monoclonal antibody W1. AB - Treatment of small cells derived from the basal layer of bovine esophageal epithelium, with Triton X-100, urea and sonication resulted in a nuclear residue that was used as an immunogen for generation of monoclonal antibodies directed against nuclear components. One such antibody, designated W1, was found to label the nuclei of all cells examined. In interphase cells, the target antigen of antibody W1 was diffusely distributed in the nucleus. During metaphase, however, the W1 antigen formed prominent crescents at the poles of the mitotic spindle, diminished gradually in anaphase, and finally redistributed into the regenerating daughter nuclei. Western blotting with antibody W1 yielded a prominent polypeptide of M(r) approximately 230,000. The amino acid sequence, deduced from the nucleotide sequence of several overlapping cDNA clones that span the entire coding region, revealed that the W1 polypeptide was identical to the Nuclear Mitotic Apparatus (NuMA) protein, with a long alpha-helical central core flanked by two nonhelical domains. Interestingly, most cDNA sequences were identical to each other, except for six sequence blocks which were either inserted or deleted in individual cDNA clones. Analysis of the cDNA sequences of various clones, coupled with polymerase chain reaction amplification of cellular mRNA and genomic Southern blotting with region-specific probes, all indicated that multiple mRNA species were present in U-251 human glioma cells, derived from alternative splicing of the RNA transcript from a single NuMA/W1 gene. Besides the predominant form of the mRNA giving rise to the polypeptide of M(r) approximately 230,000, two other forms of mRNA, which arise as a result of alternative splicing and which use different translation termination codons, may yield lower molecular weight polypeptide products. Consistent with this notion, polypeptides of M(r) approximately 195,000 and approximately 194,000 have been observed in this and other studies on the NuMA/W1 protein. These data suggest that multiple isoforms of the NuMA polypeptides generated by alternative mRNA splicing may play some important functions which remain to be characterized. PMID- 8505360 TI - Mitotic block in HeLa cells by vinblastine: ultrastructural changes in kinetochore-microtubule attachment and in centrosomes. AB - Previous work from this laboratory has indicated that very low concentrations of vinblastine block HeLa cells at mitosis in the presence of a full complement of microtubules and without major disruption of spindle organization. In the present study we analyzed the structural organization of mitotic spindle microtubules, chromosomes and centrosomes by electron microscopy after incubating HeLa cells for one cell cycle with 2 nM vinblastine. We found that mitotic block of HeLa cells by vinblastine was associated with alterations of the fine structure of the spindle that were subtle but profound in their apparent consequences. The cell cycle was blocked in a stage that resembled prometaphase or metaphase; chromosomes had not undergone anaphase segregation. Neither the structure of the microtubules nor the structure of the kinetochores was detectably altered by the drug. However, the number of microtubules attached to kinetochores was decreased significantly. In addition, the centrosomes were altered; the normal close association of mother and daughter centriole was lost, numerous membranous vesicles were found in the centrosomal region, and many centrioles exhibited abnormal ultrastructure and had microtubules coursing through their interiors. These findings are consistent with our previous results and indicate that inhibition of the polymerization dynamics of mitotic spindle microtubules and perhaps of centriole microtubules, rather than microtubule depolymerization, is responsible for the mitotic inhibition by vinblastine. PMID- 8505361 TI - Selective interactions of cells with crystal surfaces. Implications for the mechanism of cell adhesion. AB - In this study we have characterized the mode of cell adhesion to calcite and calcium (R,R)-tartrate tetrahydrate crystals. The use of crystals as adhesion substrata was motivated by their well-established chemical nature and structurally defined surfaces. We show that calcite binds A6 Xenopus laevis epithelial cells rapidly and efficiently, most likely via surface-adsorbed proteins. Surface topology had only a limited effect on the adhesive interactions. Calcium (R,R)-tartrate tetrahydrate crystals exhibits two chemically equivalent, yet structurally distinct faces that differ mainly in the surface distribution of their lattice water molecules and charges. However, despite the gross similarity between the two faces striking differences were noted in their adhesive behavior. One of the faces was highly adhesive for cells, leading to protein-independent attachment and spreading followed by cell death. In contrast, cell adhesion to the other surface of tartrate was slow (> 24 h) and apparently mediated by RGD-containing protein(s). It was further shown that the latter face of tartrate crystals could be "conditioned" by long (24 h) incubation with serum-containing medium, after which it becomes highly adhesive. The results presented here indicate that crystal surfaces may serve as excellent, structurally defined, substrata for cell adhesion, that cell binding may occur directly or via RGD-containing proteins and that cell adhesion may be dramatically modulated by variations in surface structure. The implications of the results to the mechanism of cell-substratum adhesion are discussed. PMID- 8505362 TI - Internal lamin structures within G1 nuclei of human dermal fibroblasts. AB - The nuclear lamina is a mesh-like network of fibres subjacent to the inner nuclear membrane that is believed to be involved in the specific spatial reorganisation of chromatin after mitosis. To determine how the lamina might be involved in chromatin reorganisation, we have performed indirect immunofluorescence studies on quiescent and proliferating human dermal fibroblasts (HDF). Two monoclonal antibodies recognising human lamins A and C and three different fixation methods were employed. In indirect immunofluorescence studies, cultures of quiescent cells displayed a uniform perinuclear distribution of the antibodies. In proliferating cultures two distinct populations of cells were observed: one population displayed a typical perinuclear antibody distribution, while the second population displayed an unusual pattern consisting of a series of spots and fibres within the nucleus. By inducing cell-cycle synchrony in cultures we were able to determine that the unusual internal distribution of the lamin antibodies was restricted to cells in G1. Optical sectioning and 3-D reconstruction of the lamina structures in G1 nuclei was performed with a confocal laser scanning microscope (CLSM). This revealed that the internal lamin structures consisted of small foci and fibres proliferating throughout the nucleus. These structures were shown to be closely associated with areas of condensed chromatin but not nuclear membrane. As cells progress towards S phase the internal lamin foci disappear. PMID- 8505363 TI - Localization of the RNA polymerase I transcription factor hUBF during the cell cycle. AB - Autoantibodies directed against nucleoli that recognized a doublet of 97-94 kDa in HeLa nuclear protein extracts were identified. The two polypeptides bound equal amounts of antibody, and each was recognized by antibodies affinity purified using the other polypeptide. These antigens were localized in the secondary constriction of PtK1 cells, i.e. the nucleolar organizer regions (NORs) where ribosomal genes accumulate. They were observed in human cells in the same sites as the NOR-silver-stained proteins. The molecular mass of the antigens, their characteristics in Western blotting and their localization in nucleoli and NORs during mitosis are consistent with them being RNA polymerase I transcriptional factor, UBF. This identification was confirmed on Western blotted proteins by their identical labelling patterns, using these autoantibodies and an anti-mUBF antibody that had been previously described. We obtained definitive evidence that these autoantibodies recognize UBF by the strong positive labelling of purified hUBF (1 to 4 ng). During interphase, these autoantibodies directed against UBF labelled in a folded filament pattern as small beads that may correspond to individual transcriptional units. In electron microscopy, the antibodies were observed in the dense fibrillar component (DFC) of the nucleoli and at the periphery of the fibrillar centers (FCs). At the end of G2 phase, transcription inactivation was concomitant with the gathering of UBF at mitotic NORs. UBF was not equally distributed between NORs in human cells: some NORs scored negative (2 to 4) and the intensity of labelling of positive NORs (6 to 8) differed. In confocal microscopy, 3-dimensional analysis of mitosis indicated that UBF remained associated with NORs during all mitotic stages and that there was equal partition of UBF between the daughter cells. The relationship between proteins associated with the NORs and ribosomal gene transcription is discussed. PMID- 8505364 TI - Composite microtubules of the axon: quantitative analysis of tyrosinated and acetylated tubulin along individual axonal microtubules. AB - We have shown previously, using immunoelectron microscopy, that axonal microtubules (MTs) are composite, consisting of distinct domains that differ in their content of tyrosinated alpha-tubulin (tyr-tubulin). Here, we extend these studies using a novel preparation that permits visualization of individual axonal MTs over distances of several tens of micrometers using conventional immunofluorescence procedures. Neurons are cultured on a substratum of poly lysine and laminin and then extracted with a MT stabilizing solution containing Triton X-100 and NaCl. These extraction conditions cause a loosening of the axonal MT array so that individual MTs separate from each other for variable distances along their length. We call this phenomenon fraying. Within the axon shaft, individual MTs can often be traced for several tens of micrometers, but fraying is most extensive in the distal 100-200 microns of the axon, where individual MTs can frequently be traced for distances of 50 to 100 microns or more to their plus ends. In some cases MTs separate completely from the axon, permitting visualization of both of their ends. Double-staining of frayed preparations with various combinations of antibodies against tyr-tubulin, acetylated alpha-tubulin (Ac-tubulin) or beta-tubulin, clearly revealed the composite nature of axonal MTs. Composite MTs consisted of two distinct domains, one that was relatively rich in tyr-tubulin and poor in Ac-tubulin, and the other that was relatively poor in tyr-tubulin and rich in Ac-tubulin. The transition between these domains was relatively abrupt, with the tyr-tubulin-rich domain extending from the transition to the plus-end of the MT. Quantitative analyses of fluorescence intensity along individual MTs using digital image processing revealed that the relative amount of tyr-tubulin increased by approximately 800% across the transition, whereas the relative amount of Ac-tubulin decreased by approximately 60%. Within the tyr-tubulin-rich domains, the relative amount of tyr-tubulin was generally not constant, but increased from the transition to the plus-end of the MT in a nonlinear manner. We propose that the specific pattern of variation in the extent of post-translational modification along an individual MT represents a snapshot of that polymer's growth history. PMID- 8505365 TI - Quantitative analysis of stress fiber orientation during corneal wound contraction. AB - Previous studies of actin and actin-binding proteins in corneal myofibroblasts suggest the development of a contractile apparatus composed, in part, of F-actin micro-filament bundles, i.e. stress fibers. To better understand the mechanics of wound contraction and the relationship between microfilament bundles and wound closure, we have analyzed the spatial and temporal organization of stress fibers during the process of corneal wound healing. Rabbit corneas (26 eyes) received 6 mm full-thickness, central incisions and were studied at various times for F actin organization using en bloc (whole cornea) staining with FITC-phalloidin, as well as conventional histological techniques. 3-D datasets (z-series of 40 en face optical sections, 1 micron steps) were collected using the Biorad MRC-600 laser scanning confocal microscope at various regions within the wound. At 7 days, 3-D analysis showed randomly oriented, interconnected F-actin filament bundles (stress fibers). Between 7 and 28 days, stress fibers appeared to organize gradually into planes parallel to the wound surface, with a large population achieving a final orientation nearly parallel to the long axis of the wound. Using Fourier Transform analysis techniques, an orientation index (OI) was calculated to quantitate global fiber orientation at each time point. Analysis of variance demonstrated a significant change (P < 0.001) in overall stress fiber orientation from a random distribution at day 7 to an alignment more parallel to the lateral wound borders at day 28. Overall, these data suggest that stress fibers undergo temporal changes in spatial organization that correlate with wound closure, and that wound closure does not involve the development of previously described contractile or tractional forces aligned directly across the wound. PMID- 8505366 TI - CD44 expression on murine tissues. AB - CD44 is a cell surface glycoprotein found on lymphoid and epithelial cells. Its primary function on lymphocytes and macrophages is to mediate interaction with endothelium, while its function on epithelial cells is not known. The protein has many different forms, generated by alternative mRNA splicing and by post translational modification, which may mediate different functions. During previous work on murine lung tumor cells, mAb 133-13A was isolated and shown to recognize a surface glycoprotein, P100, of 90-100 x 10(3) M(r). Amino acid sequence analysis of purified P100 indicates that it is CD44. Since few data exist to indicate which forms of CD44 are present in different normal tissues, mAb 133-13A was used to analyze CD44 expression in mouse tissue. Quantitative data on the distribution of CD44(P100) in mice show that spleen, thymus, liver, intestine, uterus and choroid of the eye are major sites of expression. In addition, epithelia of adrenals, esophagus and trachea are CD44(P100) positive. Previous work on human cell lines has implicated a high molecular mass (130-160 x 10(3) M(r)) form of the glycoprotein as the form expressed in epithelial cells and carcinomas. Isolation of CD44 proteins from lymphoid tissues in the mouse indicate that, as in human lymphoid tissue, the low molecular mass form (80-90 x 10(3) M(r)) is predominately expressed. These data show that both small (approximately 81 x 10(3) M(r)) and large forms of the glycoprotein are expressed in basal epithelia of esophagus and trachea and in salivary gland, while only the small form is expressed in epithelium of the adrenal cortex and in the murine lung and mammary carcinomas studied. While these data cannot distinguish between specific splice variants, they show that the large forms of CD44 are minor components in normal tissue and seem to be found only in basal epithelium. The CD44 of low M(r) found in epithelial tissues is probably associated with lymphoid cell types in the tissues. PMID- 8505367 TI - Gamma-tubulin reorganization during mouse fertilization and early development. AB - gamma-Tubulin, a component of spindle pole bodies in fungal cells and pericentriolar material in vertebrate cells, is thought to play a role in the nucleation of microtubule growth and to define their polarity. In contrast to the adult somatic cells, microtubules are nucleated in the absence of centrioles in mammalian oocytes and early embryos. By studying acentriolar mouse oocytes and their early development following fertilization, we show that gamma-tubulin antibody crossreacts with a 50,000 M(r) protein in unfertilized mouse oocytes and demonstrate that gamma-tubulin distribution is rearranged dramatically during fertilization. In unfertilized mouse oocytes, gamma-tubulin is concentrated in the broad spindle poles of meiotic spindle (MII) and as the distinct foci which form the centers of the cytoplasmic microtubule asters (cytasters). The integrity of these gamma-tubulin foci and their cytoplasmic location is maintained during the drug- or cold-induced depolymerization of microtubules. gamma-Tubulin is also found in the basal body of the mouse sperm. During fertilization, the gamma tubulin is found at the cytastral centers as well as in the incorporated sperm basal body complex, and the gamma-tubulin foci coalesce at the perinuclear microtubule organizing regions of the two pronuclei at the first mitotic prophase. During mitosis, gamma-tubulin is found associated with broad bands that form the poles of the first mitotic spindle. By the late preimplantation stage, when newly generated centrioles have been reported to arise, gamma-tubulin remains localized at the centrosome of mitotic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505368 TI - A scale associated protein of Apedinella radians (Pedinellophyceae) and its possible role in the adhesion of surface components. AB - Monoclonal antibodies have been generated against cell surface components of the unicellular phytoflagellate Apedinella radians (Pedinellophyceae). One monoclonal antibody, designated Arg 1E5/1B1, labels a scale associated protein (SAP) of 145 kDa. Immunofluorescence microscopy of whole cells as well as immunoelectron microscopy of whole cell mounts and thin sections using Arg 1E5/1B1 have shown that the SAP is located on the proximal surface of body scales and spine-scales. Its specific location suggests that the SAP may play a role in the adhesion of these surface components to the cell membrane and/or to one another. The potential of monoclonal antibody Arg 1E5/1B1 as a tool to study cell surface morphogenesis and the role of the endomembrane system in A. radians is discussed. PMID- 8505369 TI - A alpha and B beta chains of fibrinogen stimulate proliferation of human fibroblasts. AB - During blood coagulation and wound healing, fibrinogen polymerises to form a fibrin matrix, providing a substratum over which connective tissue cells migrate and proliferate. Although a number of growth factors have been implicated in this process, a possible role for the fibrin(ogen) molecules themselves has not been considered. In this study we have investigated the ability of the constituent chains of fibrin(ogen) to induce fibroblast replication. Fibrinogen chains (A alpha 1, A alpha 2, B beta and gamma) were separated by cation exchange chromatography and their mitogenic activity was assessed before and after treatment with thrombin. The A alpha 1, A alpha 2 and B beta chains where all found to stimulate fibroblast replication (23 +/- 2.9%, 29.2 +/- 5.3% and 31.4 +/ 5% stimulation above control, respectively) and on the addition of thrombin this activity was enhanced. No activity was observed in the gamma chain before or after treatment with thrombin. These results indicate that growth promoting activity is inherent in fibrin(ogen) structure, suggesting a novel mechanism for fibroblast proliferation during wound healing. PMID- 8505370 TI - Three-dimensional imaging of living neurons and glia with the atomic force microscope. AB - The atomic force microscope (AFM) was used to directly image hippocampal neurons and glia. Using chemically fixed and living cells it was possible to reconstruct three-dimensional cell structure and detect sub-cellular features such as the nucleus, mitochondria and filaments. By repeatedly scanning a single living cell we observed the movement of filaments beneath the cell membrane. Furthermore, by controlling the force applied to the scanning tip, nanosurgery was performed to selectively remove cells from the culture substratum. Thus, the atomic force microscope offers the opportunity to gain three-dimensional information about living cells and to observe the behavior of cellular components by imaging through the intact cell membrane. PMID- 8505371 TI - Specific responses of axons and dendrites to cytoskeleton perturbations: an in vitro study. AB - Several factors can influence the development of axons and dendrites in vitro. Some of these factors modify the adhesion of neurons to their substratum. We have previously shown that the threshold of neuron-substratum adhesion necessary for initiation and elongation of dendrites is higher than that required for axonal growth. To explain this difference we propose that, in order to antagonize actin driven surface tension, axons primarily rely on the compression forces of microtubules whereas dendrites rely on adhesion. This model was tested by seeding the cells in conditions allowing the development either of axons or of axons and dendrites, then adding cytochalasin B or nocodazole 1 hour or 24 hours after plating. The addition of cytochalasin B, which depolymerizes actin filaments and thus reduces actin-tensile forces, increases the length of both axons and dendrites, indicating that both axons and dendrites have to antagonize surface tension in order to elongate. The addition of nocodazole, which acts primarily on microtubules, slightly reduces dendrite elongation and totally abolishes axonal growth. Similar results are obtained when the drugs are added 1 or 24 hours after plating, suggesting that the same mechanisms are at work both in initiation and in elongation. Finally, we find that in the presence of cytochalasin B axons adopt a curly morphology, a fact that could be explained by the importance of tensile forces in antagonizing the asymmetry created by polarized microtubules presenting a uniform minus/plus orientation. PMID- 8505372 TI - Patterns in Dictyostelium discoideum: the role of myosin II in the transition from the unicellular to the multicellular phase. AB - Dictyostelium discoideum amoebae which lack the myosin II gene are motile and aggregate to form rudimentary mounds, but do not undergo further morphological development (Manstein et al., 1989). Here we use scanning electron microscopy, light microscopy, immunofluorescence and computer analysis of time-lapse video films to study how D. discoideum myosin null cells of strains HS2205 and HS2206 aggregate. Myosin null cells are sufficiently coordinated in their movements to form two-dimensional aggregation streams, although mutant cells within streams lack the elongated shape and parallel orientation of wild-type strains. In the wild-type, cell movements are coordinated, cells usually joining streams that spiral inwards and upwards as the mound extends into the standing papilla. In the aggregates of mutant strains, cell movements are chaotic, only occasionally forming short-term spirals that rotate at less than half the speed of wild-type spirals and frequently change direction. Unlike the situation in the wild-type where spirals continue with mound elongation, cells within the mutant mound eventually cease translocation altogether as the terminal shape of the mound is reached and only intracellular particle movement is observed. Scanning electron micrographs show that the surface of the wild-type mound consists of flattened cells which fit neatly together. The myosin null cell mound has an uneven surface, the orientation of the cells is chaotic and no tip is formed. This is consistent with the results of synergy experiments in which myosin null cells were absent from the tips of chimeric HS2205/AX2 slugs and pre-culminates. Immunofluorescence microscopy using prespore and spore cell markers reveals that a prestalk/prespore pattern forms within the mutant mound but that terminal spore differentiation is incomplete. These results are discussed in relation to the role of myosin II in aggregation and morphogenesis. PMID- 8505373 TI - Fibroblasts expressing mouse c locus tyrosinase produce an authentic enzyme and synthesize phaeomelanin. AB - Recent advances in the study of the molecular biology of mouse pigmentation have led to the discovery of a family of proteins involved in the control of melanin synthesis. It has been confirmed that the product of the mouse c (albino) locus is the key melanogenic enzyme tyrosinase, but study of its function and regulation have been hampered by the presence of closely related proteins within melanin-synthesising cells. To overcome these problems, we have established lines of mouse fibroblasts expressing the c locus mouse tyrosinase. Here we describe characterisation of the tyrosinase synthesised by these cells and demonstrate considerable similarity between the expressed tyrosinase and the native enzyme. The expressed tyrosinase is proteolytically cleaved to produce membrane-bound and soluble forms of the expected molecular mass and is rich in N-linked carbohydrate, suggesting that melanocytic differentiation is not a prerequisite for post-translational modification of the protein. The expressed enzyme has tyrosinase activity, but not catalase or dopachrome tautomerase activity, confirming that it is an authentic tyrosinase. Transfected fibroblasts expressing tyrosinase are shown to share several physiological characteristics with melanoma cell lines, including increased pigmentation and tyrosinase activity in response to increased cell density. Since tyrosinase is expressed under a heterologous promoter, these shared characteristics probably reflect translational or post translational controls that operate in both non-melanocytic and melanocytic cell types. We demonstrate that pigmented fibroblasts contain the melanin synthesis intermediates 5-S-cysteinyldopa and 5-S-glutathionyl-dopa, and produce a phaeomelanin-like pigment, but do not contain detectable eumelanin. Expression of tyrosine is therefore sufficient for the synthesis of a form of melanin pigment in fibroblasts. PMID- 8505374 TI - Cell membrane-associated proteoglycans mediate extramedullar myeloid proliferation in granulomatous inflammatory reactions to schistosome eggs. AB - In chronic murine schistosomiasis, extramedullar myelopoiesis was observed, with proliferation of myeloid cells in liver parenchyma and in periovular granulomas. We have studied the question of whether cells obtained from granulomatous connective tissue may act as myelopoietic stroma, supporting long-term myeloid proliferation. Primary cell lines (GR) were obtained in vitro from periovular granulomas, induced in mouse livers by Schistosoma mansoni infection. These cells were characterized as myofibroblasts, and represent liver connective tissue cells involved in fibro-granulomatous reactions. They were able to sustain survival and proliferation of the multipotent myeloid cell lines FDC-P1 and DA-1 (dependent on interleukin-3 and/or granulocyte-macrophage colony stimulating factor, GM-CSF) without the addition of exogenous growth factors. This stimulation was dependent upon myeloid cell attachment to the GR cell layer; GR cell-conditioned medium had no activity. Primary murine skin fibroblasts could not sustain myelopoiesis. The endogenous growth-factor was identified as GM-CSF by neutralization assays with monoclonal antibodies. The stimulation of myelopoiesis occurred also when GR cells had been fixed with glutardialdehyde. The observed stimulatory activity was dependent upon heparan sulphate proteoglycans (HSPGs) associated with GR cell membranes. It could be dislodged from the cell layer with heparin or a high salt buffer. Our results indicate a molecular interaction between endogenous growth factor and HSPGs; this interaction may be responsible for the stabilization and presentation of growth factors in myelopoietic stromas, mediating extramedullar proliferation of myeloid cells in periovular granulomas. PMID- 8505375 TI - Mycelial and syncytial growth in Schizosaccharomyces pombe induced by novel septation mutations. AB - Mutation in the gene sep1+ of the unicellular fission yeast Schizosaccharomyces pombe impairs cell separation after cytokinesis and confers a branching mycelial morphology. The mutant is not defective in cell wall beta-glucanase activity but shows increased sensitivity to Ca2+ and Mg2+, and increased resistance to the microtubule inhibitor benomyl. The mycelial growth of sep1-1 provides a convenient method for the examination of the polar growth pattern and for pedigree analysis as demonstrated by the segregation of mating types in the homothallic microhyphae. sep1 is closely linked to ade1 (0.94 cM) on the right arm of chromosome II. The ts mutation spl1-1 confers a bent cell shape and causes aberrant septum formation at the restrictive temperature. sep1+ and spl1+ perform closely related functions as their mutant alleles interact with each other and with another septation mutant cdc4-8. These functions may overlap with certain cytoskeletal processes and with the determination of cell polarity because the triple mutant forms huge multinucleate syncytia with promiscuous branching and rare septum formation. PMID- 8505376 TI - Amplification of the Golgi complex in MDCK cells secreting human growth hormone. AB - MDCK cells were transfected with pXGH5, a plasmid containing the human growth hormone (hGH) gene, and permanently expressing cell lines were selected. Clone 3A cells, which secrete quantities of hGH through both apical and basolateral surfaces, were examined in detail. Immunofluorescence analysis using anti-hGH antibody revealed bright perinuclear staining coinciding with the area delineated by anti-p52 kDa protein (a resident Golgi protein) antibody. There appeared to be less Golgi-specific fluorescence in untransfected cells. This difference correlated with an increased amount of 52 kDa in the clone 3A cells. Morphometric analysis was performed on electron micrographs of clone 3A and untransfected cells using the fractionator to estimate average number of Golgi stacks per cell, and values were statistically analyzed. It was found that clone 3A cells contained 3.3 and untransfected cells 1.6 stacks (P < or = 0.005), respectively. When clone 3A cells were placed into defined medium, the synthesis and secretion of hGH declined 4-fold, and the number of Golgi stacks also decreased to the untransfected level within seven days. The number of Golgi stacks per untransfected cell was not affected by the presence of exogenous hGH, indicating that Golgi amplification was directly related to secretory demand. Generation times and cell volumes were identical for both cell types under all growth conditions. In addition, the kinetics of protein secretion from radiolabelled cells demonstrated that clone 3A cells generally secrete lower amounts of endogenously synthesized apical proteins than do untransfected cells, while basolateral secretion remains the same. In both cases hGH comprised only about 10% of total secretory proteins, so that the increase in total protein secretion did not seem to warrant the two-fold elaboration of Golgi by 3A cells. But there might be significant amounts of hGH which traverse the Golgi to end up in lysosomes, rather than being secreted, leading to Golgi amplification. PMID- 8505377 TI - Receptor-mediated endocytosis of transferrin at the blood-brain barrier. AB - Rat brains were perfuse with a transferrin-peroxidase conjugate (Tf-HRP) to characterize morphologically the endocytic pathway of transferrin in blood-brain barrier endothelial cells. Electron microscopic evaluation of rat brains perfused with Tf-HRP at 4 degrees C and subsequently warmed to 37 degrees C for brief periods of time (2 minutes) showed sequestration of Tf-HRP in clathrin coated pits and vesicles on the luminal membrane of the brain endothelium. After 5 minutes of warming, diaminobenzidine (DAB) reaction product was present in vesicular structures 250-500 nm in diameter and in associated tubules morphologically identified as large or sorting endosomes. Recycling endosomes were also heavily labelled at this time point. Almost no DAB reaction product remained in the cerebral endothelial cells when the warming period was longer than 15 minutes. Other rat brains were perfused with Tf-HRP at 30 degrees C for 15 minutes prior to fixation and DAB cytochemistry. In these studies, brain endothelial cells contained large amounts of DAB reaction product, mostly localized in 50-100 nm vesicles and tubules, often in the Golgi region of the cells. Coated pits and vesicles and large endosomes were also heavily labelled. Transcytosis of Tf-HRP was not identified in either perfusion protocol. Ultrastructural, indirect immunocytochemical localization of transferrin receptors showed that the transferrin receptor is highly polarized at the blood brain barrier and is localized only on the apical membrane, in contrast to other polarized epithelial cells, like hepatocytes, in which the receptor is present on the basolateral membrane. The evidence supports an iron transport model in which iron-loaded transferrin is taken up by receptor-mediated endocytosis at the luminal membrane of brain capillaries. The iron then dissociates from transferrin in endosomal compartments and is transcytosed by unknown mechanisms, while the transferrin is retroendocytosed. PMID- 8505378 TI - Presence of a nuclear lamina in pachytene spermatocytes of the rat. AB - The nuclear lamina is a karyoskeletal structure located at the periphery of cell nuclei. The major constituents are the lamins, which belong to the evolutionarily conserved multigene family of intermediate filament proteins. Lamins show a conspicuous cell type-specific expression pattern. The majority of somatic cells of vertebrates express A-type (lamins A and C) as well as B-type (lamins B1 and B2) lamins. Although a lamina structure has been demonstrated to be a ubiquitous component of somatic nuclei its existence in certain meiotic stages during spermatogenesis has been a matter of debate. In this study, we investigated the expression of lamins in rat spermatogenic cells using immunological and protein chemical methods. We report on the presence of a nuclear lamina structure in rat pachytene spermatocytes. With the aid of a novel broad-reacting lamin antibody we have demonstrated the expression of a protein that is closely related, if not identical, to lamin B1. PMID- 8505379 TI - Differential replication capacities of G1 and S-phase extracts from sea urchin eggs. AB - Sea urchin eggs are arrested in G1 of the first mitotic cell cycle. Fertilization triggers release from G1 arrest and the onset of DNA synthesis about 20 minutes later, even when protein synthesis is blocked. Here we describe extracts from eggs and S-phase embryos that reproduce this stage-specific pattern of DNA synthesis. Fertilized egg extracts formed nuclear membranes around decondensed Xenopus sperm chromatin whereas unfertilized egg extracts did not. Aphidicolin sensitive deoxynucleotide incorporation was high in extracts of fertilized S phase eggs and low in those of unfertilized eggs. In contrast, single-stranded DNA templates directed high rates of incorporation in both unfertilized and fertilized egg extracts, suggesting that the stage-specific activities in nuclear DNA synthesis is restricted to initiation on double-stranded DNA. Mixing experiments showed that unfertilized eggs do not contain a dominant inhibitor of replication, nor does fertilization induce the appearance of a soluble, dominant activator. PMID- 8505380 TI - Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. AB - We have identified a novel autoantibody specificity in scleroderma that we term anti-chromo. These antibodies recognize several chromosomal antigens with apparent molecular mass of between 23 and 25 kDa, as determined by immunoblots. Anti-chromo autoantibodies occur in 10-15% of sera from patients with anti centromere antibodies (ACA). We used anti-chromo antibodies to screen a human expression library and obtained cDNA clones encoding a 25 kDa chromosomal autoantigen. DNA sequence analysis reveals this protein to be a human homologue of HP1, a heterochromatin protein of Drosophila melanogaster. We designate our cloned protein HP1Hs alpha. Epitope mapping experiments using both human and Drosophila HP1 reveal that anti-chromo antibodies target a region at the amino terminus of the protein. This region contains a conserved motif, the chromo domain (or HP1/Pc box), first recognized by comparison of Drosophila HP1 with the Polycomb gene product. Both proteins are thought to play a role in creating chromatin structures in which gene expression is suppressed. Anti-chromo thus defines a novel type of autoantibody that recognizes a conserved structural motif found on a number of chromosomal proteins. PMID- 8505381 TI - Abnormal anaphase resolution (aar): a locus required for progression through mitosis in Drosophila. AB - We describe a new mitotic locus of Drosophila melanogaster required for the progression through mitosis in the syncytial embryo and in late larval development. The locus aar (abnormal anaphase resolution) maps to the cytological interval 85E7-F16 and was identified by two alleles. The aar1 allele causes pupal lethality. Larval neuroblasts show an elevated mitotic index with high chromosome condensation and stretched and lagging chromatids during anaphase. aar2 produces fully viable but sterile females. aar1/aar2 females lay eggs that develop mitotic figures with similar abnormalities to those observed in neuroblasts. Indirect immunofluorescence of these embryos indicates that the centrosome cycle appears normal, although some abnormal spindle microtubules can be seen during mitosis. PMID- 8505382 TI - Morphological and biochemical analyses of contractile proteins (actin, myosin, caldesmon and tropomyosin) in normal and transformed cells. AB - The expression and intracellular distribution of four contractile proteins (actin, myosin, caldesmon and tropomyosin) in normal fibroblasts and their transformed counterparts by Rous or avian sarcoma virus were compared. By analyzing the isoformal expression of actin, caldesmon and tropomyosin using two dimensional gel electrophoresis, only tropomyosin showed significant alteration in its isoformal expression accompanied by transformation. Morphological study revealed that in normal cells, myosin, caldesmon and tropomyosin were distributed periodically along stress fibers, but were excluded from focal adhesions (adhesion plaques), at which stress fibers terminate. By contrast, the contractile proteins were concentrated within the protrusions of the ventral cell surface of transformed cells, which are cell-adhesive structures with high motility (podosomes). Regional analysis indicated that the contractile proteins do not show diffuse distribution within podosomes. Myosin, some caldesmon and tropomyosin in association with F-actin were localized in the region surrounding the core domains of podosomes. A major part of the caldesmon was, however, located in the core domain with short F-actin bundles. In order to compare the stability and the molecular organization of stress fibers with that of the short F-actin bundles within podosomes, the dorsal plasma membranes of the cells were removed by lysis and squirting. Then, the ruptured cells were treated with various buffers containing high salt, ATP or Ca2+/calmodulin. Myosin, caldesmon and tropomyosin were strongly associated with stress fibers of the ruptured normal fibroblasts even in a buffer containing high salt or Ca2+/calmodulin. On the other hand, myosin and tropomyosin within podosomes were easily extracted by lysis and squirting. And, the remaining caldesmon in podosomes was separated from the short F-actin bundles with high salt or Ca2+/calmodulin buffer. The present findings suggest that the high motility of podosomes from transformed cells is based on the actomyosin system, and that the stable adherence of focal adhesions of normal cells is due to a lack of this system. The accumulation of contractile proteins and their dynamic association within podosomes might be the cause of the short half-life of the structure. In relation to its localization in the core domain of podosomes without myosin and tropomyosin, the function of caldesmon has been discussed. PMID- 8505383 TI - The amyotrophic lateral sclerosis client and the issues surrounding mechanical ventilation. PMID- 8505384 TI - Insight, initiative, and imagination in nursing administration. PMID- 8505385 TI - Critical thinking and theory-based practice. PMID- 8505386 TI - Helping students learn to make ethical decisions. PMID- 8505388 TI - Nursing education and critical thinking: interplay of content and thinking. PMID- 8505387 TI - A critical assessment of critical thinking in nursing education. PMID- 8505389 TI - Critical thinking in psychiatric nursing in the decade of the brain. PMID- 8505390 TI - Affective learning: one door to critical thinking. PMID- 8505391 TI - Alternative views on defining critical thinking through the nursing process. PMID- 8505392 TI - A modification of Benner's hierarchy of clinical practice: the development of clinical intuition in the novice trauma nurse. PMID- 8505393 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Selecting the antibiotic. AB - Variations in antibiotic pharmacokinetics and pharmacodynamics allow therapy to be readily adapted to the outpatient setting. Factors to be taken into account when designing an outpatient parenteral regimen include minimal inhibitory and bactericidal concentrations, post-antibiotic effect, half-life, protein binding, drug stability, IM versus i.v. administration, and continuous versus intermittent infusion. PMID- 8505394 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Advances in i.v. delivery. AB - Physicians who prescribe outpatient parenteral antibiotic therapy must remain abreast of advances in intravenous catheters and infusion pumps so they can select equipment that realizes the full potential of therapy and suits the patient's needs for comfort, reliability, and safety. The cost of equipment and installation can vary greatly and is thus another important consideration when choosing these devices. PMID- 8505395 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Pediatric considerations. AB - Outpatient parenteral antibiotic therapy (OPAT) is less threatening to children than in-hospital treatment and most likely reduces the risk of nosocomial infection. Most pediatric infections can be treated in the home if patients are medically stable, parents are motivated to help with therapy, and appropriate resources, such as skilled pediatric nursing, are available. The cost of pediatric OPAT is similar to that of adult OPAT. PMID- 8505396 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Quality assurance. AB - At present, there are no accepted guidelines for quality assurance in the outpatient setting, although they are being developed. Greater emphasis is being placed on ongoing rather than retrospective improvement of quality, as measured by the care-giving process and outcome. Thus, programs need to incorporate sound methods for teamwork, communication, and documentation of services. PMID- 8505397 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Costs and benefits. AB - The costs of outpatient parenteral antibiotic therapy are outweighed by the benefits to all involved: provider, payer, patient, and society. Simple comparisons of inpatient and outpatient charges are not a true measure of costs. Recent in-depth cost-benefit analyses reveal a significant saving when indirect benefits, such as increased productivity and quality of life, are included. Even so, financial issues remain to be addressed. PMID- 8505398 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Reimbursement. AB - Reimbursement for outpatient parenteral antibiotic therapy (OPAT), like that for all health care, is regulated by a multitude of private and public policies. Not all payers reimburse all aspects of OPAT, and with those that do, obtaining payment can be a daunting task. A key to prompt payment is the correct billing code. An overview of office-based, home-based, and hospital-based OPAT reimbursement is presented. PMID- 8505399 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. Legal issues. AB - The tremendous growth of outpatient services has spurred closer legal scrutiny of patient referrals to physician-owned companies (self-referral). Federal "safe harbor" regulations protect certain arrangements, but much of the law remains vague. Future legislation is likely to be more specific, however. Physicians should obtain legal counsel before entering into any ownership or investment opportunities in home infusion therapy. PMID- 8505400 TI - Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. The team concept. AB - The delivery of outpatient parenteral antibiotic therapy is a team effort that, at minimum, requires a physician, a nurse, and a pharmacist. Other specialists may be added as needed. The team may be structured in several different ways, but two basic models emerge: physician-directed and nonphysician-directed. Whatever the structure, the physician should maintain a leadership role in the care of the patient. PMID- 8505401 TI - Simultaneous optimization of pH and micelle concentration in micellar liquid chromatography. AB - A retention model for ionizable compounds in micellar liquid chromatography is derived and verified. The use of the model for the prediction of retention is illustrated and appropriate optimization strategies for the separation of ionizable compounds in Micellar Liquid Chromatography are discussed. PMID- 8505402 TI - The supercritical fluid extraction of polar drugs (sulphonamides) from inert matrices and meat animal products. AB - The objective of this study was to examine the extension of supercritical fluid extraction (SFE) to the extraction of polar drugs. The ultimate aim was to extract veterinary residues from food animal products and thereby demonstrate the versatility of SFE. This technique is shown to have many facets that require careful thought and understanding if it is to be successfully used. Our initial studies indicate that polar drugs may be readily solubilized from relatively inert matrices such as sand, with high recoveries and very little discrimination between related compounds while using only moderate extraction conditions and times. SFE of the same drugs from spiked chicken liver and swine muscle is significantly more difficult and requires more drastic conditions. Close to complete recoveries are achieved for some drugs, while considerably less is found in the worst case. For sulphamerazine, sulphamethizole, sulphamethazine, sulphamethoxypyridazine, sulphamethoxazole, and the major metabolite N4-acetyl sulphamethoxazole, the recoveries are 97, 66, 94, 79, 53, and 65%, respectively, from spiked liver and 95, 27, 86, 91, 96 and 70%, respectively, from spiked swine muscle. Incurred sulphamethazine is recovered from swine muscle in good general agreement with the reference values provided. PMID- 8505403 TI - Elevated cerebrospinal fluid IgA in humans and rats is not associated with secretory component. AB - Immunoglobulin A (IgA) is transported across mucosal tissue membranes covalently bound to secretory component (SC). To determine if this receptor-mediated process also occurs at central nervous system (CNS) boundaries, cerebrospinal fluid (CSF) and serum from patients with CNS neuroinflammatory disease were analyzed for IgA and SC. Excess CSF IgA was detected in six of 24 patients, but no significant CSF SC was detected. In a parallel study using a rat model with normal brain barriers, inactivated lymphocytic choriomeningitis virus was microinfused into CSF. Elevated CSF IgA was detected in four of six rats, yet the proportion of secretory IgA was again insignificant compared to normal exocrine fluids (bile, semen). There does not appear to be a secretory IgA immune system at CNS boundaries and elevated CSF IgA is attributed to intrathecal synthesis. PMID- 8505404 TI - Brain reactive monoclonal auto-antibodies: production and characterization. AB - To determine the role of auto-antibodies in the pathogenesis of neuropsychiatric manifestations of systemic lupus erythematosus (NP-SLE), it will be necessary to characterize the diversity of auto-antibodies that exist. This can be done by producing a library of monoclonal, brain-reactive auto-antibodies. From such a library the antigens to which the antibodies bind, and whether there are any interesting relations between these antigens, can be determined. Behavioral effects can also be investigated. Toward these ends, brain-reactive monoclonal auto-antibodies (BRMA) were produced. The production and characterization of two monoclonal antibodies is presented in this study. PMID- 8505405 TI - Absence of oligoclonally restricted immunoglobulins in tears from multiple sclerosis patients. AB - To study the extent of systemic immunodysregulation in multiple sclerosis (MS) we measured immunoglobulin (Ig)G, A, and M levels and studied their migrational properties after agarose isoelectric focusing in serum, cerebrospinal fluid (CSF) and tear samples from 18 MS patients, 17 patients with other neurological diseases (OND), and tears and serum samples from ten normal controls (NC). A slight elevation of total IgG, IgM and IgA levels was detected in tears from patients with MS and OND compared to NC. Of the five patients (two MS, three OND) that showed IgG oligoclonal bands (OCB) in tears, only one MS patient showed unique bands in tears not seen in the paired CSF and serum. We never found IgA, and IgM OCB in serum, CSF or tear samples. Our results suggest that polyclonal Igs are systemically elevated during chronic neurological inflammatory diseases. Oligoclonal Ig in MS, although occasionally detectable in tears, is mainly confined to the central nervous system and appears restricted to class G. PMID- 8505406 TI - Potential role of thymoma and other mediastinal tumors in the pathogenesis of myasthenia gravis. AB - Ten non-myasthenic thymoma patients and 12 patients with other mediastinal tumors were compared with 19 myasthenic thymoma patients with regard to an increase in circulating CD4+CD8+ cells and the presence of anti-acetylcholine receptor and anti-skeletal muscle antibodies. Although seven non-myasthenic thymoma patients showed positive results, the proportion of myasthenic thymoma patients who were positive for more than one parameter was significantly larger than that of non myasthenic thymoma patients (89% vs. 40%). Moreover, one patient with a non thymomatous mediastinal tumor showing a high CD4+CD8+ cell level had a recent history of seronegative myasthenia gravis. The results indicate that measurements of these parameters may predict the risk of the development of MG in patients with thymoma and other mediastinal tumors. PMID- 8505407 TI - Activation of the alternative complement pathway and production of factor H by skeletal myotubes. AB - Skeletal muscle myotubes from neonatal rats were used to study the interaction of skeletal muscle with complement. Serum from guinea pig, rabbit, and human, in the absence of muscle-specific antibody, caused creatine phosphokinase release, which required activation of the terminal complement cascade. Cleavage of serum C3 and Factor B in the presence of myotubes was dependent on Mg2+, but not Ca2+, and C3 cleavage occurred only in the presence of Factor B. Rat myotubes caused significant consumption of C8 and C9 in rat serum, which also required Mg2+, but not Ca2+. All of these findings are typical of a tissue capable of activating the alternative pathway. In addition, the C2 myotube cell line was shown to produce Factor H, an inhibitory protein of the alternative pathway, as demonstrated by Factor H mRNA expression and immunoprecipitation of the protein. PMID- 8505408 TI - Cytoimmunological abnormalities in cerebrospinal fluid in early stages of HIV-1 infection often precede changes in blood. AB - We determined the proportions of CD2+, CD4+ and CD8+ lymphocytes in the cerebrospinal fluid (CSF) and paired blood samples of 19 neurologically examined subjects with CDC II/III stage HIV-1 infection and 21 controls. Using a three layer indirect immunoperoxidase technique, we found that 16 HIV-1-infected subjects had an abnormally low CD4+/CD8+ ratio of the CSF due to a decrease in the proportion of CD4+ T cells and/or an increase in that of CD8+ lymphocytes. Compared to controls, in the HIV-1-infected group this ratio appeared to be lower in both CSF and blood (P < 0.001). The changes of lymphocyte subpopulations were more marked in the CSF than in blood, and no clear associations were found between the findings of paired CSF and blood samples. Cytological examination of the CSF revealed that 12 of 14 patients had an elevated total cell count and an abnormal differential count with a predominance of mononuclear phagocytes. An elevated number and/or proportion of enlarged lymphoid cells was found in most cases. The total cell counts, and total numbers of mononuclear phagocytes and lymphocytes of the patients were higher than in controls (P < 0.001). Our study shows that the changes in CSF lymphocyte subsets often precede those in blood and that immunological events in the central nervous system (CNS) are not directly reflected in peripheral blood. Cytoimmunological abnormalities in the CSF of individuals with early stages of HIV-1 infection indicate subclinical CNS involvement, and may be of importance for therapeutic considerations. PMID- 8505409 TI - Transferred T lymphocytes are compromised when the donor is pretreated with beta endorphin. AB - A single intracerebroventricular (i.c.v.) injection of 14 pmol of beta-endorphin into 6-7-week-old BALB/c (+/+) donor mice, 24 h prior to isolation of their T lymphocytes for use for reconstitution of athymic BALB/c (nu/nu) nude mice, altered the immuno-protective effect of adoptive transfer against an intracerebral (i.c.) infection with a temperature-sensitive mutant of vesicular stomatitis virus (tsG31 KS5 VSV). Simultaneous injection of beta-endorphin and naloxone into donor animals negated the opiate effects on splenic lymphocytes. T lymphocytes, isolated from beta-endorphin-treated donors, and then depleted with anti-asialo GM1 antiserum and complement failed to demonstrate the detrimental effects of beta-endorphin. PMID- 8505410 TI - Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor. AB - Experimental autoimmune myasthenia gravis (EAMG), which to some extent represents an experimental counterpart of human myasthenia gravis, can be induced by inoculation of various animal species and strains with acetylcholine receptor (AChR). The oral administration of Torpedo AChR to Lewis rats prior to immunization with Torpedo AChR and complete Freund's adjuvant resulted in prevention or delay in the onset of EAMG. Levels of anti-Torpedo AChR antibodies in serum measured by radioimmunoassay were lower in orally tolerant compared to control animals. The model might have a relevance for studying the pathogenesis and immunotherapy of human myasthenia gravis. PMID- 8505411 TI - The origin of the autoimmune disease-resistant LER rat: an outcross between the buffalo and autoimmune disease-prone Lewis inbred rat strains. AB - The Lewis (LEW) rat strain is highly susceptible to a large number of experimentally induced inflammatory and autoimmune diseases. The Lewis resistant (LER) rat strain, which reportedly arose as a spontaneous mutation in a closed colony of LEW rats, is resistant to many of these disorders. The mechanism of resistance is not yet clear. We report the analysis of 19 simple dinucleotide repeat polymorphisms in 13 rat strains including the LEW/N and LER/N rat strains. The LEW/N and LER/N alleles were the same in only 42% of cases. For all of the other polymorphisms, the LER/N and Buffalo (BUF/N) rat strain alleles were identical. These data provide evidence that the LER strain did not arise as a spontaneous mutation in the LEW strain but is the result of an outcross between the LEW and BUF rat strains. The LER rat strain is now a recombinant inbred rat strain. This information should facilitate the genetic analysis of the loci responsible for resistance to experimental autoimmune disease in the LER rat. PMID- 8505412 TI - Advances in the understanding and treatment of multiple sclerosis. Boston, Massachusetts, USA, 28-29 October 1992. AB - Basic and applied research on multiple sclerosis (MS) has become increasingly focused on the development and testing of new therapeutic agents for this devastating disease. After a generation or more of exposing patients to non specific immunoregulatory and other agents that have been, at best, of minimum benefit and significant potential or actual toxicity, attention has turned to attempts to identify treatment modalities that might be used in a more specific, effective and safe fashion. This trend has not been lost on the emerging biotechnology industry, which tends to view MS as both a disease to be explored on its own and as a disease whose solution may also open doors into other chronic diseases of purported autoimmune etiology, such as rheumatoid arthritis, type I diabetes, and others. These trends toward an increasing biotechnological approach to MS, coupled with an academic and industrial focus on the disease, were the clear motivations behind a recent two-day conference entitled "Advances in the Understanding and Treatment of Multiple Sclerosis" held in Boston and sponsored by a commercial meeting planner, International Business Communications USA Conferences, Inc. PMID- 8505413 TI - Occipital seizures provoked by intermittent light stimulation: ictal and interictal findings. AB - Occipital seizures provoked by intermittent light stimulation are rare events described in patients with symptomatic and idiopathic epilepsy as well as in nonepileptic individuals. We observed five patients ranging in age from 10 to 32 years, who presented with focal seizures provoked by photic stimuli; none of them had demonstrable occipital lesions. Four patients were epileptic, and one was nonepileptic. Three patients had occipital epilepsy with visual seizures; one had generalized epilepsy with absence attacks; the nonepileptic had migraine. In the patients with visual seizures, interictal EEGs showed occipital foci in two cases and bilateral spontaneous and evoked spikes as well as generalized discharges in the third. The patient with absence attacks had generalized discharges. The migraine patient had a normal EEG. Ictal EEGs showed a focal lateralized theta activity at the onset of seizures in three patients, in one a fast recruiting rhythm intermixed with generalized paroxysms reflex to blinking, and in the other a rapid bioccipital fast rhythm spreading to the anterior regions. Occipital seizures provoked by intermittent light stimulation probably constitute a rare type of photosensitivity, sometimes appearing in occipital epilepsies, generalized epilepsies, and migraine. PMID- 8505414 TI - Effects of antiepileptic drug treatment on the background frequency of EEGs in epileptic patients. AB - The effect of changing antiepileptic drug concentrations within the therapeutic range on the EEGs of epileptic subjects was studied by quantitative EEG analysis. Twenty-seven patients had administration of one or more drugs discontinued on admission to the hospital for prolonged video/EEG monitoring, and drug levels were correlated daily with the simultaneous EEG background. Phenytoin, alone or in combination with other drugs, led to significant changes in the mean EEG background frequency and increased the percentage of power in the theta and delta bands. In the plasma ranges studied, carbamazepine, phenobarbital, and valproic acid did not lead to significant change in the EEG background frequency; however, the number of subjects taking these medications was small. PMID- 8505415 TI - The UCLA Epilepsy Program: historical review 1960-1992. PMID- 8505416 TI - Technology and equipment review. Evoked potential instrumentation, Part II. PMID- 8505417 TI - Influence of bile on cellular integrity and beta-galactosidase activity of Lactobacillus acidophilus. AB - The influence of bile on beta-galactosidase activity, cellular integrity, cellular retention of beta-galactosidase, and cellular permeability of five strains of Lactobacillus acidophilus was investigated. The five strains were also compared for bile tolerance. Two strains, 223 and 4356, were significantly less resistant to bile than the others (107, NCFM, and 606). beta-Galactosidase activity of all five strains was significantly higher in the presence of .3% oxgall than in its absence. Strain 107 showed the highest increase of enzyme activity in the presence of oxgall. Cells were not lysed in the presence of .3% oxgall, and beta-galactosidase was retained inside the cell even after extended incubation (60 min) in the presence of .3% oxgall. However, material that absorbed light at 260 nm leaked from the cells in the presence of oxgall. We concluded that, in the presence of bile, the permeability of cells of L. acidophilus increased, permitting more substrate to enter the cells, thus increasing the beta-galactosidase activity of whole cells. PMID- 8505418 TI - Enzymatic assay for the combined determination of plasmin plus plasminogen in milk: revisited. AB - The ability of beta-lactoglobulin variants A and B, alpha-lactalbumin, and BSA to inhibit plasmin plus plasminogen activity was examined. Data showed that beta lactoglobulin A at concentrations of .2 and 1 mg/ml inhibited plasmin plus plasminogen activity by 18 and 54%. beta-Lactoglobulin B had no effect on plasmin plus plasminogen activity. At concentrations of .2 and 1 mg/ml, BSA inhibited plasmin plus plasminogen activity by 25 and 63%. alpha-Lactalbumin at concentrations of .2 and 1 mg/ml caused 1.9 and 20% inhibition of plasmin plus plasminogen activity. These data, collectively, suggest that existing methodology for measuring plasmin activity in milk serum underestimates real plasmin activity in milk. Underestimation is more pronounced in samples with high whey protein content (late lactation milk and milk obtained from mastitic quarters). To avoid this problem, we have modified the existing methodology. Our modification allows plasmin determination without interference from whey proteins and other plasmin inhibitors that are present in the serum fraction of bovine milk. PMID- 8505419 TI - Responses of the bovine mammary artery to angiotensins. AB - The main objective of our study was to determine whether angiotensins cause vasoconstriction of mammary arterial segments in vitro. Once this action was established, its specificity was determined. Mammary arterial sections were obtained from lactating cattle at slaughter. Vessel sections were placed in a gravity-fed, closed, perfusion apparatus, and flow was measured by a transit-time flow sensor mounted in-line. Treatments were administered by injection into a leurlock port located proximal to the sensor. Angiotensins I, II, and III induced a dose-dependent vasoconstriction of arterial segments at concentrations of 5 x 10(-10) to 5 x 10(-6) M. Angiotensin II receptor antagonists, Saralisin and (Sarl, Thr8)-angiotensin II (5 x 10(-8) M)), inhibited vasoconstriction induced by angiotensins I, II, and III. The angiotensin-converting enzyme inhibitor, Captopril (5 x 10(-8) M), inhibited angiotensin I vasoconstriction, thereby showing that the vasoconstriction by angiotensin I was mediated through its conversion to angiotensin II. These data demonstrated that the mammary artery of lactating cows is responsive to the angiotensin family. Furthermore, mammary arteries contain angiotensin-converting enzyme and specific receptors for angiotensin II. This system may be important in the normal physiological regulation of mammary gland blood flow of lactating cows. PMID- 8505420 TI - Opsonization of Staphylococcus aureus by bovine immunoglobulin isotypes. AB - The ability of specific bovine Ig isotypes to enhance phagocytosis of Staphylococcus aureus by polymorphonuclear neutrophils was studied. Polymorphonuclear neutrophils were isolated from the blood of 14 lactating Holstein cows. Antibodies against S. aureus M10 were produced by two Holstein cows immunized via intramuscular injections and injections in the area of the supramammary lymph node with M10 emulsified in dextran sulfate. The IgG1, IgG2, and IgM were prepared from immune sera. Fluorescein-labeled, formalin-killed S. aureus M10 were opsonized with the respective isotypes prior to incubation with polymorphonuclear neutrophils. Percentage of polymorphonuclear neutrophils phagocytosing averaged 37.4, 1.1, 15.9, and 9.4% for immune sera, IgG1, IgG2, and IgM, using a M10: polymorphonuclear neutrophils ratio of 10:1; and 77.1, 1.8, 32.1, and 57.9 using a 40:1 ratio. When IgG1 was incubated with either IgG2 or IgM, phagocytosis was reduced to 10.0 and 5.0%, respectively, using the 10:1 ratio and 24.2 and 44.7%, respectively, using the 40:1 ratio. Significant variation occurred among cows in the ability of polymorphonuclear neutrophils to undergo phagocytosis independent of isotype and S. aureus M10: polymorphonuclear neutrophil ratio. These data show that IgG2 and IgM are opsonic for bovine polymorphonuclear neutrophils and that IgG1 inhibits the activity of both. These results will be helpful to determine immunization protocols to solicit synthesis of bovine IgM and IgG2 specific for S. aureus. PMID- 8505421 TI - Effect of a Staphylococcus aureus bacterin on serum antibody, new infection, and mammary histology in nonlactating dairy cows. AB - The influence of a Staphylococcus aureus mastitis vaccine on immunologic status and rate of new IMI was evaluated. At drying off, cows were vaccinated, either intramuscularly or subcutaneously in the area of the supramammary lymph node, or were left as unvaccinated controls; vaccinates received booster injections at 6 wk. Serum antibody concentrations, bacteriologic status, and SCC of quarter milk samples were determined. Four weeks after revaccination, cows were challenged by intramammary infusion of S. aureus and then killed 24 to 72 h later. Mean serum antistaphylococcal antibody titer of vaccinated cows during the trial was 4.7 fold that of controls. Challenge resulted in IMI rates of 92, 36, and 60% for control cows, cows vaccinated intramuscularly, and cows vaccinated in the area of the supramammary lymph node. Vaccination by either route had no influence on mammary parenchymal tissue components compared with controls; however, leukocyte infiltration was greater in quarters from cows vaccinated in the area of the supramammary lymph node than in quarters from unvaccinated controls. Plasma cell populations producing IgG1, IgG2, IgA, and IgM were greatest in quarters of cows vaccinated in the area of the supramammary lymph node followed by those in quarters of cows vaccinated intramuscularly and control cows. PMID- 8505422 TI - Path analysis for seven postpartum disorders of Holstein cows. AB - Path analysis and multiple logistic regression with an extrabinomial variation error term (to account for herd) were used to model seven postpartum clinical disorders of dairy cows and factors related to the calf. Data were from 7761 lactation records from 34 commercial herds in the vicinity of Cornell University. Stillbirth increased the odds of developing metritis and retained placenta. The odds of developing dystocia and mastitis were lower when the sex of the calf was female. However, cows that twinned had increased odds of developing dystocia and retained placenta. Dystocia was related to an increase in the odds of retained placenta. Milk fever, dystocia, and ketosis each increased the odds of developing left-displaced abomasum. Postpartum periods with dystocia, retained placenta, or ketosis had increased odds of metritis. Two interaction terms involved parity: stillbirth for milk fever and retained placenta for ketosis. The extrabinomial variation error term contributed to the fit in all models. PMID- 8505423 TI - Management risk factors associated with calf diarrhea in Michigan dairy herds. AB - A study was conducted to examine the relationships between various dairy herd management practices and the monthly incidence density of calf diarrhea. The data were collected during a recent 2-yr prospective cohort study by the Michigan National Animal Health Monitoring System. The data were statistically analyzed, and predictive models were developed. For herds with 10 to 49 adults cows, variables predicting an increase in the incidence of diarrhea in calves were number of young stock in the herd, incidence of respiratory disease in calves, and cumulative incidence of vaccinations for calves to prevent diarrheal disease. Increased numbers of routine veterinary visits to the farm were associated with decreased incidence of calf diarrhea. For herds with 50 to 99 adult cows, the positive predictor variable was incidence of respiratory disease in calves. Negative predictor variables were used of individual calving areas and removal of bedding between calvings. For herds with 100 to 199 adult cows, positive predictor variables were cumulative incidence of vaccinations for calves to prevent diarrheal disease and number of young stock in the herd. For herds with > 200 adult cows, positive predictor variables were use of individual calving areas, number of routine veterinary visits to the farm, and incidence of respiratory disease in calves. These variables accounted for 13.1, 17.7, 7.4, and 64.2% of the variability in the incidence of calf diarrhea in the respective herd size groups. PMID- 8505424 TI - Sources of variation in partitioning of intake energy for lactating Holstein cows. AB - Variation in energy partitioning was quantified. Data were from 34 multiparous Holstein cows using indirect respiration calorimetry during the 6th, 10th, and 14th wk postpartum. For each period, cows were placed in digestion stalls for a 6 d excreta collection, followed by two consecutive 11-h determinations of methane and heat production. Sources of variation among cows were analyzed for gross energy consumed; for fecal, urinary, CH4, heat, milk, and maintenance energies; for tissue energy balance; and for tissue partitioning. Ratios of heat production, energy balance, milk energy, and maintenance energy to intake energy were also analyzed for sources of variation. A within-period model was used that contained fixed effects of treatment, parity, season, and covariates for metabolic BW and SCM. None of the diet or parity effects were a significant source of variation in any of the variables. Season effects were only significant for milk energy and water intake. As a covariate, SCM was highly significant for all variables except energy for heat production and energy for maintenance. However, metabolic BW as a covariate was a significant effect for heat production at wk 10 and 14 postpartum. The significance of metabolic BW differed between periods for most energy partition and efficiency measures. The most significant proportion of the variation in energy utilization was attributable to the energy in the milk. PMID- 8505426 TI - Ruminal, intestinal, and total digestibilities of nutrients in cows fed diets high in fat and undegradable protein. AB - To study relationships of high undegradable intake protein and dietary fat on intestinal AA supply, the ruminal, intestinal, and total digestibilities of diets with or without added fat (5% of DM) and animal protein (blood meal: hydrolyzed feather meal, 1:1; 8% of DM) were examined with four cows in a 2 x 2 factorial design in a 4 x 4 Latin square experiment. Ruminal degradabilities were 14.9 and 18.6%, and intestinal digestibilities were 98.9 and 68.3%, respectively, for CP in blood meal and feather meal. Treatment effects on ruminal digestibilities were small. Protein supplementation increased total N intake by 29%, duodenal AA N flow by 39%, and AA N absorbed by 37%; absorption of Leu and Lys increased 60 and 33%, and absorption of Ile and Met increased 11 and 7%, respectively. Measured duodenal AA N flow (Cr2O3 marker) was 33% higher in cows cannulated adjacent to the pylorus compared with cows cannulated 100-cm distal to the pylorus, but only when cows were fed protein-supplemented diets; the estimates from those diets caused calculated microbial protein efficiency to exceed theoretical values. We postulated that blood meal and feather meal segregated near the pylorus, yielding high estimates of duodenal AA N flow. Removal of data for protein-supplemented diets obtained from cows cannulated at the pylorus yielded estimates of microbial protein synthetic efficiency consistent with literature values. Microbial synthesis of AA N was related linearly to ruminal digestion of carbohydrate. Location of intestinal cannulas may influence accuracy of nutrient flow estimates. PMID- 8505425 TI - Protein-fat bypass supplement for lactating dairy cows. AB - Holstein cows (n = 46) were fed free choice a silage mixture balanced weekly throughout lactation using 13 and 36% CP grains to individualize CP for each cow; grains contained 15 and 20% of distillers grains with solubles, respectively. Cows were blocked by parity (1 vs. > 1) and assigned at calving to receive a commercial bypass protein-fat supplement at 0 (control) or 6% of weekly projected 4% FCM yield throughout lactation. In peak lactation, supplementation raised dietary fat from 4.3 to 6.0% of DM, NE(L) from 1.64 to 1.70 Mcal/kg of DM, and undegradable protein from 42 to 47% of CP and contributed about 25 and 20% of total CP in early and late lactation. Supplement reduced forage and total DMI significantly, which negated the potential nutritional value of the supplement. Reduction in protein content of milk from supplemented cows was small but significant; BW and yields of milk, SCM, and 4% FCM were not significantly affected by treatment. Supplementation increased fat test in parity 1 cows and lowered it in older cows. In wk 5 to 8, 21 to 24, and 37 to 40 postpartum, cows consumed 100 to 116% of the NRC recommendations of undegradable protein but only 65 to 94% of degradable CP needs; NE(L) intake generally was adequate except for primiparous cows in early lactation. Supplementation lowered Lys intake in early lactation. Addition of rumen-protected fat and undegradable, high quality protein mixture to the diet of lactating cows cannot be effective if its use reduced DMI or if degradable protein intake is inadequate. PMID- 8505427 TI - Milk yield, intake, and blood traits of lactating cows fed grass silage conserved under different harvesting methods. AB - Thirty-two Holstein cows (8 primiparous) were assigned to negative control or to one of three treatments to assess three forage harvesting and conservation techniques. Forage was harvested as low moisture silage by either a cylinder-type forage harvester, a self-loading forage harvester, or a round baler. Treatment diets were fed from wk 4 to 15 of lactation and consisted of silages harvested by the respective methods supplemented with concentrate at 1.1% of BW. Unsupplemented silage harvested by a cylinder-type forage harvester was used as a control. Daily DMI was higher for cows fed supplemented heap silage cut with either a cylinder-type forage harvester (23.7 kg) or a self-loading forage harvester (22.6 kg) than for cows fed the control (20.0 kg) or supplemented round bale silage (20.1 kg). Milk yield was highest for cows fed supplemented heap silage cut with a cylinder-type forage harvester (26.6 kg/d) and lower for those fed supplemented heap silage cut with a self-loading forage harvester (22.7 kg/d) or the control (20.8 kg/d). Milk composition and digestibilities of DM, N, ADF, and energy were similar among treatments. Postfeeding NEFA concentration decreased more for control cows than for those fed supplemented silage, which was related to greater BW loss. The high milk yield for cows fed supplemented heap silage cut with a cylinder-type forage harvester could be related to a high DMI and low BW gain. PMID- 8505428 TI - Effects of recombinant bovine somatotropin under conditions of high production and heat stress. AB - The effect of bST injection on milk production of Israeli Holsteins was tested under conditions of mean production > 9000 kg/yr and climatic stress; mean maximum and minimum summer temperatures are 38 and 25 degrees C, respectively, in the Jordan Valley, located 200 m below sea level. In 1989, 111 cows were injected, and 115 cows were recorded as controls. In 1990, 108 cows were injected, and 93 cows were included as controls. Fifty-nine of the cows injected in 1990 were also injected in 1989. Production records were corrected for parity, calving month, days to first injection, and days in milk. Injection with bST increased total lactation milk production by 12%, fat production by 15%, and protein production by 13%. Injection also resulted in slight increases in fat and protein percentages. Daily milk production during the injection period was increased by 4.4 kg. Injection during the previous lactation slightly decreased production of cows injected during the following lactation. Advancing the commencement of injection from the 4th to the 2nd mo in milk did not affect total lactation production. Weight gains and dry matter intake were higher for injected cows, but body condition score was higher for the control group. Injection had no discernible effect on fertility variables. PMID- 8505429 TI - Identity and paternity testing of cattle: application of a deoxyribonucleic acid profiling protocol. AB - We have applied DNA profiling for identity and parentage studies of cattle using a standardized procedure based on synthetic micro- and minisatellite multilocus core probes in Southern blot hybridization assays. This protocol is useful for paternity analysis of cattle and for real case work (e.g., identity and paternity disputes). PMID- 8505430 TI - Graduate education for nursing students who have English as a second language. AB - Working with international students, especially those who have English as a second language, is a challenge for any educator. To date there has been little information in the nursing literature that is helpful to faculty who teach and/or mentor these students. The shared personal knowledge gained from participation in planning and providing educational options for foreign students and the empirical cognizance made possible from several years of guiding the program of studies of these students is offered as a beginning framework to other faculty. The need for research in the area is identified. PMID- 8505431 TI - The ethical quandaries of acute care nursing practice. AB - This study explored the perceptions of nurses employed in acute care nursing regarding the ethical quandaries in which they find themselves involved on a recurrent basis. Sixty-five female nurses volunteered to participate in the study. Data were collected over a 2-year period at four institutions. Qualitative methods were used to collect and analyze the data. Three categories were derived from the situational conditions described. These were exploitation, ie, nurses' concern with the inhumane treatment of seriously ill patients; exclusion, ie, the lack of attention paid to patient wishes in treatment decisions; and anguish, ie, the powerlessness and frustration felt by nurses involved in ethical situations. It was concluded that in an era of escalating, complex dilemmas, nurses are willing and motivated to engage in ethical decision-making situations, particularly when the comfort or rights of their patients are involved. The environmental barriers to this practice, however, are staggering. The barriers identified included lack of support or poorly defined mechanisms of support, time pressures, personal concerns over security, and hierarchic forces within the institution. Nurses' inability to act on behalf of patients or with regard to their individual conscience may be contributing to high turnover rates and the nursing shortage, particularly in those areas with high use of technology. PMID- 8505433 TI - Ethics and scholarly writing. PMID- 8505432 TI - The nurse's multiple commitments. AB - Nurses have multiple commitments: organizational, work, professional, job, patient, and personnel. Research has focused almost exclusively on organizational commitment and, to a lesser extent, on professional and job commitment. This fragmented approach to the study of the nurse's commitments neglects the nurse's commitment to patients. The concept of commitment needs to be clarified so that knowledge derived from research on commitment enhances our understanding of how nurses manage these multiple commitments. PMID- 8505434 TI - Professional practice. A call for mapmakers. PMID- 8505435 TI - Public policy. Friends in all places. PMID- 8505436 TI - Doctoral preparation and research productivity. PMID- 8505437 TI - The nurse executive. Surviving retrenchment. PMID- 8505438 TI - Nursing research and societal needs: political, corporate, and international perspectives. AB - Tension exists between political and public pressure for fiscal constraint in health care expenditures and the scientific community urging greater allocation of research funds. Some contend that scientists are out of touch with the rest of society. This issue is discussed from the political, corporate, and international perspectives. Nurse researchers need to examine their priorities and determine whether they are congruent with societal need. In addition, increased interaction with the public, increased involvement with the federal decision making process, and the building of research consortia and collaborative endeavors are recommended. PMID- 8505439 TI - Knowledge and beliefs regarding pain in a sample of nursing faculty. AB - Pain is a significant problem impacting between 50 per cent and 80 per cent of cancer patients and affecting overall quality of life. Studies have documented that nurses and other health care professionals are inadequately prepared to care for patients in pain. Several reasons have been identified including inadequacies in nursing and medical education, absence of curriculum content related to pain management, and faculty attitudes and beliefs related to pain. This article presents data from a cross-sectional mall survey that consisted of a self administered knowledge and beliefs questionnaire and a self-reported pain curriculum questionnaire. Faculty from 14 baccalaureate nursing schools in the United States participated in the study. The study suggests that in baccalaureate schools of nursing, faculty knowledge and beliefs about pain and the curriculum content related to pain may be less than optimal. PMID- 8505440 TI - Characteristics of registered nurses' self-directed learning projects for professional development. AB - This study examined characteristics of 88 self-directed learning (SDL) projects. The projects were completed within 6 months of the study by practicing registered nurses and pertained to some aspect of learning for professional development. The characteristics that were studied were the SDL projects' locations, planners, benefits, resources, obstacles, organization, and subject gains in knowledge and skill. Subjects reported that the home and the work place were the most frequently used locations for SDL projects. The learners themselves and groups led by professionals were responsible for 70 per cent of the planning. The two most frequently used resources were peer coworkers and conference handouts. The most frequently checked motivator for doing the projects was the anticipated ability to apply the knowledge or skill gained during learning. The leading obstacle was finding time to do the learning. The majority of the subjects reported that the projects were organized with goals, planned activities, and evaluation strategies. Most of the subjects believed that they learned a great deal from the projects and that others had also benefited from their learning. Implications are discussed. PMID- 8505441 TI - Patient autonomy in care: a theoretical framework for nursing. AB - Patient autonomy has increasingly become an issue in a health care system that often promotes dependence in decision making. The complex technology of health care creates situations in which difficult decisions need to be made by patients and their families. Nurses are important participants in that decision-making process. Models available for developing a theoretical approach to patient autonomy traditionally have been limited to ethics literature. A more recent approach to personal autonomy is Meyer's philosophical feminist perspective. Any philosophical approach to patient autonomy must be congruent with other critical nursing concepts. In addition, a model of patient autonomy for nursing must be useful for persons who operate at various functional levels. The model, Patient Autonomy in Care, based on the Meyer's model, was developed to incorporate the special vulnerability and functional needs of patients in the health care system. PMID- 8505442 TI - Dentistry's voice unheard. PMID- 8505443 TI - Litigation and post-traumatic TMD: how patients report treatment outcome. AB - Ongoing litigation may affect treatment response in patients with trauma-induced TMD. A survey of 100 patients underscores the need for comprehensive psychosocial and behavioral assessment, including evaluation of litigation status in these patients. PMID- 8505444 TI - Organizing dental study clubs: education for better patient care. AB - Direction, definition, dedication and design are the four requirements to establish a study club. Study clubs provide incentives for personal and professional growth, leading to better patient care. PMID- 8505445 TI - Pharmacist has no case in separate claim. PMID- 8505446 TI - Nevada Supreme Court overturns discipline of neurosurgeon. PMID- 8505447 TI - Taking issue on implants. PMID- 8505448 TI - Trigeminal nerve injury. PMID- 8505449 TI - Modern management of dental caries: the cutting edge is not the dental bur. AB - Treating the disease, not the symptoms, is the change in managing dental caries. As researchers supply the tools, dentists can apply more efficient and realistic methods for better patient care. PMID- 8505450 TI - Dilemmas in caries diagnosis. AB - New criteria and methods are needed to identify the changing expression of caries and to classify carious lesions into categories keyed to treatment strategies. Symposium speakers identified these problems and reviewed the changing philosophy of diagnosis. PMID- 8505451 TI - Gustatory and olfactory considerations: examination and treatment in general practice. AB - Gustatory and olfactory problems have deleterious consequences to systemic health, nutritional status and quality of life. Since patients with these problems are initially seen by dentists, they should be identified, treated and referred to other health care providers when appropriate. Care of these patients should be included in the general dental practice. PMID- 8505452 TI - Evaluating tooth color change from carbamide peroxide gel. AB - A double-blind experiment assessed the efficacy, longevity and safety of a tooth whitener in young adults. Significant color changes occurred after active treatment but were substantially reversed after one week. No permanent changes were found in either pulpal or gingival health. PMID- 8505453 TI - Determining the HIV status of patients of three HIV-positive Navy dentists. AB - The prevalence of human immunodeficiency virus infection has caused the risk of HIV transmission in the health care setting to become a major public concern. Navy medical records were reviewed to investigate the HIV status of 2,887 patients treated by three HIV-positive dentists. PMID- 8505454 TI - Obtaining pre-radiation therapy dental clearance. AB - Patients scheduled to receive radiation therapy that involves the mandible, maxilla or salivary glands should be referred for dental consultation, assessment and clearance before therapy begins. A form that aids the radiation oncologist and the dentist in patient referrals is presented. PMID- 8505455 TI - Dissociation between the wishes of terminally ill parents and decisions by their offspring. AB - OBJECTIVE: To assess the attitude and factors affecting decision-making by offspring for life-sustaining measures toward their elderly terminally ill parents. DESIGN: Survey SETTING: Acute geriatric department of a university affiliated teaching hospital. PATIENTS AND PARTICIPANTS: 108 offspring of 48 terminally ill elderly patients were interviewed. MEASUREMENTS: The attitude of offspring regarding life-sustaining measures based on a comprehensive questionnaire, administered by face-to-face interview, that included clinical, social, and religious information for each patient and social, religious, demographic, and educational information for each family member. RESULTS: A significant majority requested the continuation of fluid, nutrition, and medication (78%, 66%, 73%, respectively). A minority of 25%-29% requested the initiation of resuscitation, mechanical ventilation, and dialysis. Active euthanasia was requested by seven offspring. Factors that significantly affected offspring's decisions were the degree of religious observance and close relationship. Approximately 50% of offspring believed they knew their parents' wishes, but most of them did not comply with the parents' wishes. The offspring's preferences for themselves differed in important aspects from the requests for their parents. The great majority stated that a family member and/or the responsible physician should be involved in the decision-making process (76% and 79%, respectively). Only 2.0% suggested the participation of an ethics committee, and the court was rejected by all. CONCLUSIONS: Basic life-sustaining measures are requested for the terminally ill parents by most of the offspring. A significant minority even requested aggressive life-sustaining measures. The degree of religiosity and closeness of relationship influenced offspring's request most strongly. PMID- 8505456 TI - Prevalence and significance of electroencephalographic abnormalities in patients with suspected organic mental syndromes. AB - OBJECTIVE: To determine the prevalence of electroencephalogram (EEG) abnormalities at different levels of cognitive impairment and to assess the possible diagnostic usefulness of the test. DESIGN: Combined prospective assessment of subjects receiving EEGs and retrospective chart review of symptoms and medications. SETTING: Academic geriatric psychiatry service. PATIENTS: 350 adults age 50 and above; 312 were patients being evaluated for possible organic mental syndrome and 38 were normal controls. MEASUREMENTS: All subjects had EEGs and Mini-Mental State Examinations (MMSE) performed at the time of the EEG. EEGs were rated for the presence and type of abnormality, and subjects were stratified according to the severity of impairment. Charts were reviewed by a person blinded to EEG results to determine clinical diagnosis and medications received. MAIN RESULTS: Abnormal EEGs were significantly more common among all patients (67%) in the study than among controls (11%), and the prevalence of abnormality increased with increasing impairment. Many demented patients with equivocal impairment (42%), and most with mild-to-moderate impairment (65%) had abnormal EEGs. An abnormal EEG was not indicative of dementia even when clear cognitive impairment was present, since patients with depression frequently also had abnormal EEG results. CONCLUSIONS: These findings suggest that the EEG is a moderately sensitive but non-specific indicator of brain dysfunction in the elderly. The significance of abnormalities among patients with equivocal impairment should be more fully assessed by longitudinal follow-up to determine if greater cognitive impairment develops. PMID- 8505457 TI - A preliminary report of vitamin D and calcium metabolism in older African Americans. AB - OBJECTIVE: To determine normal serum bone-related biochemical variables in older African-Americans. DESIGN: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. SETTING: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. PARTICIPANTS: Thirty-two African-Americans aged 68 93 years and 43 white Americans aged 70-89 years. MEASUREMENTS: Twenty-five hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, and calcitonin. RESULTS: Serum 25OHD levels in 38% of the African-American men and 38% of African American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. CONCLUSIONS: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter. PMID- 8505458 TI - Do family caregivers recognize malnutrition in the frail elderly? AB - OBJECTIVE: To determine if family caregivers are aware of the severely underweight elder's risk of malnutrition and accordingly increase nutritional care efforts. DESIGN: Case-control study. PARTICIPANTS: Familial caregivers to community-dwelling elders. MEASUREMENTS: Risk of malnutrition as defined by body mass index < or = 5th percentile of the national average for elders aged 65-90. RESULTS: Compared with caregivers of elders without risk for malnutrition, caregivers to undernourished elders are significantly more likely to give elders protein supplements, to make foods accessible to elders, and to encourage and pressure the elder to eat. CONCLUSIONS: Caregivers recognize gross signs of malnutrition in elders, increase nutritional care in response, and deserve some measure of support for their claims of health expertise. PMID- 8505459 TI - The methodology of studying decline in Alzheimer's disease. AB - OBJECTIVE: To present a new model for analyzing longitudinal data. The trilinear model is superior to the commonly used linear model that includes the flawed assumption that decline is uniform throughout the course of disease--an assumption that does not correspond to clinical observations. DESIGN: A longitudinal cohort sample was used to compare the linear and trilinear models. Simulated longitudinal data were generated to assess classification errors with the trilinear model. SUBJECTS AND SETTING: The subjects were 80 patients with Alzheimer's disease tested in a hospital out-patient clinic. METHODS: The trilinear model describes Alzheimer's disease as proceeding through three periods: An initial period of stability before detectable decline, a period of decline, and a final period of stability during which there is no further detectable decline. A program for the Apple Macintosh computer is available at no charge to apply the model to data. FINDINGS: The analyses indicated that the trilinear model provides a better reflection of decline in Alzheimer's disease than does the linear model. This advantage is present whether the periods of stability reflect a "true" lack of decline or insensitivity of a measurement instrument. CONCLUSIONS: The trilinear model provides not only a more accurate estimate of the average rate of change, but also (when possible) estimates of the point at which decline begins and ends. Also, more detailed comparisons of tests could be made by using the trilinear parameters. The trilinear model would benefit researchers engaged in longitudinal research of progressive disorders. PMID- 8505460 TI - Flexible bronchoscopy as a diagnostic tool in the evaluation of pulmonary tuberculosis in an elderly population. AB - OBJECTIVE: This study intends to determine what role fiberoptic bronchoscopy (FOB) plays in the diagnosis of tuberculosis (TB), particularly in a geriatric population. DESIGN: Cases of tuberculosis reported to the Tennessee Department of Health during the years 1989 and 1990 were divided into two age groups: Group A (< 65 years) and Group B (> or = 65 years). Natural sputum smears and cultures positive for M. tuberculosis (M. TB) in each group were compared with FOB specimens, acid-fast bacilli (AFB) smears and cultures. Data were analyzed by chi square tests of independence for each year, then compared to determine statistical significance. SETTING AND PATIENTS: Of the 601 TB cases reported to the State of Tennessee in 1989, 285 patients were in Group A and 316 in Group B. For 1990, 525 cases were reported, 269 in Group A and 256 in Group B. All cases met CDC-approved criteria for diagnosis of tuberculosis. MEASUREMENTS: The number of positive AFB smears and M. TB cultures were compared in each group. In cases with sputum negative but FOB specimens positive for TB, identification was made by FOB only. MAIN RESULTS: In Group A, 26 (9.1%) were diagnosed by FOB; only eight of these had positive sputum cultures. In Group B, 77 (24.4%) were diagnosed by FOB. Of these, 23 had positive sputum cultures; the remaining 54 patients (17.1%) had diagnoses based on FOB alone. In 1990, 269 cases of TB were reported in Group A. Of these, 38 (14.1%) were diagnosed by FOB. There were 256 TB cases reported among Group B, 83 (32.4%) of which were diagnosed by FOB. Of these 83 cases, 60 (23.4%) were diagnosed by FOB only. While no statistically significant difference was seen between the 1989 and 1990 rates of TB diagnosis by FOB for those in Group A (age < 65), the difference in rates for those in Group B (age > or = 65) was statistically significant (P < 0.05). CONCLUSIONS: A steady increase in the use of FOB as a diagnostic tool was noted, suggesting that a significant number (19.9%) of geriatric TB cases might have been missed without the aid of FOB. While the exact reason for its increased utilization is not known, this study indicates that FOB has become a more important source of diagnosis in pulmonary TB, particularly among the elderly. PMID- 8505461 TI - Urinary retention in the elderly: a study of 100 hospitalized patients. AB - OBJECTIVE: To estimate the prevalence of incomplete bladder emptying by the elderly and to determine its significance and its relationship to overflow incontinence. DESIGN: Survey comparing groups with and without incomplete bladder emptying. SETTING: A geriatric hospital ward. PATIENTS: One hundred patients who were consecutively admitted, with an average age of 82.6 years. MEASUREMENTS: A physical examination, perineal examination, micturition assessment, and evaluation of the post-voiding residual urine volume (PRUV) by ultrasonography at day 1 and day 8 following admission. One-channel cystometry and urine cultures were also done. Between-group comparison was performed between groups R (ie, PRUV greater than 50 mL) and C (ie, PRUV less than 50 mL). MAIN RESULTS: The prevalence of PRUV greater than 50 mL was 34%. Group R patients presented with greater dependency; death was the final outcome of hospitalization in 36% of these cases (vs only 9% in group C). A high PRUV was not correlated with urinary tract infection or renal failure, but there was a strong, almost significant trend toward incontinence being more prevalent in R (57%) than in C (38%) (P = 0.06). Group R presented a hypotonic bladder in 45% of cases, evidenced by cystometry, versus 6% in group C. CONCLUSIONS: In cases with a high PRUV, the utmost caution is necessary both in the diagnosis of overflow incontinence and in establishing a therapeutic approach. Incomplete bladder emptying is associated with a poor prognosis. PMID- 8505462 TI - Effects of age, gender and education on selected neuropsychological tests in an elderly community cohort. AB - OBJECTIVE: To establish population-based data, with special emphasis on the effects of age, gender, and education, for eight, widely used neuropsychological tests in a community-dwelling cohort of normal and cognitively impaired older adults. DESIGN: A population-based observational study. SETTING: Examinations were performed in a research clinic by specially trained staff during a 1988-1992 evaluation for osteoporosis. PARTICIPANTS: 1,692 community-dwelling subjects, aged 55 to 94 years, who were members of the Rancho Bernardo Heart and Chronic Disease Study initiated in 1972. The mean age for men was 73.9 years (SD 9.3) and for women, 73.5 (SD 9.1). OUTCOME MEASURES: Eight neuropsychological tests were used to measure cognitive functions. Analysis of variance and post hoc contrasts were performed to determine the effects of age, gender, education, and their interactions on performance on these tests. RESULTS: Performance on all tests decreased progressively, without leveling off, from the youngest, age 55, to the oldest, age 94. Women performed better on verbal tasks and men on tests of visuospatial, visuoconceptual, and mental control functions. Performances of men on several tests declined more rapidly with advancing age than those of women. Both men and women with some college education performed better on most tests than men and women with high school educations, and the rate of decline with age was sometimes slower in the college-educated group. Only the savings score from the Visual Reproduction Test, which is a measure of rate of forgetting, and the scores of short-term recall derived from the Selective Reminding Test (Buschke Fuld) were unaffected by educational attainment. CONCLUSIONS: In a community dwelling cohort, including normal and cognitively impaired elderly men and women, advancing age is accompanied by decline in cognitive functions as measured by neuropsychological tests. This decline is slower in women and in college-educated subjects. Two cognitive indices were unaffected by education, and these may be especially useful in cross-cultural studies. PMID- 8505463 TI - Acute autonomic responses to postural change, Valsalva maneuver, and paced breathing in older type II diabetic men. AB - PURPOSE: To examine the effects of advanced age and diabetes on the response to standard tests of cardiovascular reflexes. DESIGN: Group comparison. SETTING: Psychophysiology laboratory, Department of Veterans Affairs Medical Center. PATIENTS: Sixteen elderly male (67-81 years old) non-insulin dependent diabetic subjects without hypertension and nine elderly male (63-77 years old) controls. MAIN OUTCOME MEASURES: Continuous (beat-by-beat) measures of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance were studied during tests of Valsalva maneuver, deep breathing, and postural change from sitting to standing. RESULTS: In comparison with elderly controls, the diabetic patients showed altered cardiovascular responses in measures of heart rate variability during Valsalva and standing. None of the subjects evidenced frank postural hypotension, but there was a greater fall in diastolic blood pressure immediately after standing for the diabetic patients compared with the controls. There was also a significant relationship between this response and decreased heart rate variability during Valsalva. CONCLUSIONS: Older type II diabetic patients compared with healthy controls had mild cardiovascular abnormalities. These results parallel those of studies comparing younger diabetics and controls. PMID- 8505464 TI - Functional decline in Alzheimer's disease: a longitudinal study. AB - OBJECTIVE: To assess the reliability of activities of daily living (ADL) measures and determine the rate and pattern of longitudinal ADL change in patients with Alzheimer's disease (AD). DESIGN: Longitudinal study with evaluations every 6 months. SETTING: Alzheimer's Disease Research Center Clinics at Mount Sinai Medical Center, New York, and the Veterans Affairs Medical Center, Bronx, New York. PATIENTS: 104 patients meeting NINCDS-ADRDA criteria for probable AD were followed an average of 31 months. MEASUREMENTS: Physical Self-Maintenance Scale (PSMS) and Instrumental Activities of Daily Living Scale (IADLS) of Lawton and Brody and the Blessed Test of Information, Memory, and Concentration. RESULTS: For men there was inconsistency over time in the decision about whether or not some IADLS items such as "Laundry" were appropriate for a given patient. Test retest and inter-rater reliabilities were high for all PSMS items and for IADLS items that were judged to be appropriate. IADLS scores changed an average of 2.06 (+/- 3.27) points annually, and change scores were smaller for patients with severe dementia. PSMS scores changed an average of 2.44 (+/- 3.87) points annually with virtually all change occurring in severely demented patients. There was a marked ceiling effect for the IADLS and a curvilinear relationship of PSMS annual change with PSMS baseline. CONCLUSIONS: Both PSMS and IADLS measures can be reliable in AD patients, but better IADLS items for males need to be developed. IADLS scores are sensitive to change in mild and moderately demented AD patients, while PSMS scores are sensitive to change in more severely demented patients. PMID- 8505465 TI - Falls: an examination of three reporting methods in nursing homes. AB - OBJECTIVE: To examine the concordance of various fall reporting methods and to use the results to recommend a preferred method of ascertaining fall frequency for residents of nursing homes, both for research and in the collection of federally mandated nursing home data. DESIGN: A cohort study followed for 858 patient months, with a mean individual follow-up of 6.6 months. MEASUREMENTS: Falls were independently ascertained monthly by three methods: review of administrative incident reports, nursing home chart abstraction, and structured interview of subjects. Concordance of events was assessed using measures of simple agreement and Kendall's Tau-b. Simple correlation and multiple regression were used to evaluate the relation of age, sex, gender, depression, mental status, and functional status with degree of concordance between self-reported falls and chart-recorded falls. SETTING: One academic and six community nursing homes in San Antonio, Texas. PARTICIPANTS: 131 long-stay nursing home residents, greater than 60 years of age, dependent in at least two activities of daily living, and mildly cognitively impaired. RESULTS: Falls were ascertained in 74 of the 131 individuals; 53 subjects fell 124 times by incident report, 58 had 140 falls according to chart review, and 66 subjects self-reported 232 falls. Greatest agreement between reporting methods was shown for incident report and chart review, with a Kendall's Tau-b of 0.88; self-report and chart-review agreement was 0.56; and self-report and incident agreement was 0.53. Estimated total fall events were more often (P = 0.001) identified by chart review (92%) than incident report (82%). Although concordance was higher for non-fallers, no significant relationships were observed between concordance and age, sex, race, depression, mental status, and functional status. Also, there was no systematic relationship between length of follow-up and degree of concordance. CONCLUSIONS: Fall frequency varies by ascertainment method, with chart review reflecting a greater number of fall events than the traditionally counted incident reports. PMID- 8505466 TI - Rehabilitation outcome of older patients with end-stage renal disease and lower extremity amputation. PMID- 8505467 TI - Clozapine treatment of parkinsonism with psychosis. PMID- 8505468 TI - Older women's health. Task Force on Older Women's Health. American Geriatrics Society. PMID- 8505469 TI - Reflections on the offspring's ethical role in decisions for incompetent patients: a response to Sonnenblick, Friedlander, and Steinberg. PMID- 8505470 TI - Medical futility of CPR. PMID- 8505471 TI - Vignette on enteral feeding. PMID- 8505472 TI - Tuberous sclerosis: the next step. PMID- 8505473 TI - Brainstem glioma: I. Pathology, clinical features, and therapy. AB - Gliomas that arise in the brain stem have been associated with a poor prognosis. Diagnostic neuroimaging readily identifies the tumor as it extends between normal brainstem structures. Histologic sampling of tumor with stereotactic methods is notoriously unreliable in establishing a definitive prognosis. Clinical trials that incorporate high-dose chemotherapy, autologous bone marrow rescue, and irradiation hold promise of better tumor control by overcoming the inaccessibility of the central nervous system to standard doses of chemotherapy. We review the pathology, clinical features, neuroimaging features, and current therapeutic concepts relative to brainstem glioma. The pediatric neurologist has a pivotal role in identifying and monitoring children with this malignancy. PMID- 8505474 TI - A T-to-G mutation at nucleotide pair 8993 in mitochondrial DNA in a patient with Leigh's syndrome. AB - We studied a patient with Leigh's syndrome using neurophysiologic, radiologic, enzymatic, biochemical, and molecular analysis. Her clinical course had started with acute encephalopathic symptoms at 7 months of age. With repeated remission and exacerbation, she developed hypotonia and symptoms of brainstem dysfunction, such as irregular respiration and swallowing difficulty. These symptoms were followed by epileptic seizures, including simple partial seizures and tonic spasms. Both serum lactate and serum pyruvate levels were elevated, and deficient activity was detected in cytochrome c oxidase in her quadriceps femoris muscle. From the early stages, we noted an abnormality in the auditory brainstem response and visual evoked potentials, and an abnormal symmetrical low-density area in the basal ganglia on the computed tomographic scan. We found a mitochondrial DNA point mutation at 8993 in blood samples from both the patient and her mother using a simple polymerase chain reaction method. The ratio of wild and mutant mitochondrial DNA calculated densitometrically on polymerase chain reaction products was 56.6% in the patient's blood cells and 8.4% in her mother's. This patient's disorder was thought to be maternally inherited Leigh's syndrome. Her brother had died of the identical clinical features at 1 year 9 months of age. PMID- 8505476 TI - The value of the Mini-Mental State Examination in childhood: a preliminary study. AB - The Mini-Mental State Examination (MMSE), a screening test of higher mental function, has been modified slightly for use in a pediatric outpatient setting. The test, which takes 5 to 10 minutes to administer, covers a range of cognitive functions including orientation, attention-concentration, memory, language, and constructional ability. In a preliminary study, we have found that the test can be applied from the age of 4 years. Highly significant correlations were found between the MMSE score and chronologic age (r = .57; P < .001), reading age (r = .79; P < .001), and mental age (r = .83; P < .001). MMSE scores reach a plateau at a mental age of approximately 10 years. The MMSE is a suitable instrument for screening higher mental function in children at the age of 4 years and above and can be readily incorporated into the routine neurologic examination of children. PMID- 8505475 TI - Alexander's disease: clues to diagnosis. AB - The clinical, radiologic, neurophysiologic, and pathologic findings in 10 children with histologically proven Alexander's disease are described, and the presence of two broad clinical subgroups is confirmed. Macrocephaly, regression, and seizures are found in the infantile form, whereas bulbar signs predominate the so-called juvenile form. None of the clinical or neurophysiologic findings is pathognomonic, and radiologic features suggesting the diagnosis are not present in all cases. However, the combination of abnormalities may suggest the diagnosis and justify histologic confirmation. PMID- 8505477 TI - Brainstem and cerebellar vermis involvement in autistic children. AB - Recent reports have suggested functional abnormalities of the brain stem in autistic children, and structural abnormalities have also been reported. We obtained magnetic resonance imaging (MRI) scans for 21 autistic children and compared them with 21 control MRI scans. The areas of the brain stem and cerebellar vermis were measured using midsagittal images. The brain stem and cerebellar vermis lobules VIII to X were found to be significantly smaller in autistic children. A positive correlation between the size of the brain stem and cerebellar vermis was observed in the autistic children. This correlation was not observed in the control children. This suggests that the size of the brain stem and cerebellar vermis are anatomically altered in autistic children and that growth of the brain stem and cerebellar vermis in autistic children is different from normal children. PMID- 8505478 TI - Successful treatment of hereditary trembling chin with botulinum toxin. AB - Hereditary trembling chin is an autosomal dominant condition characterized by recurrent bouts of tremor involving the chin. These episodes are precipitated by emotional upset. There has been considerable debate about the gravity of this condition. This may be a benign movement disorder; however, the rhythmic trembling of mentalis at rest or during times of stress in these patients is often misinterpreted as betraying an incipient emotional upset. For this reason, some patients with this condition may find it socially disabling. We have recently successfully treated one such family with regular botulinum toxin injections to the mentalis muscle. PMID- 8505479 TI - Effects of methylphenidate on impulsive responding in children with attention deficit hyperactivity disorder. AB - The present investigation examined the effects of methylphenidate on impulsivity in children with attention-deficit hyperactivity disorder (ADHD). A task was designed to measure empirically the ADHD child's proclivity to blurt out incorrect answers before giving a final and/or correct response. Twenty-six ADHD children referred for double-blind placebo-controlled assessment of medication responsiveness and 14 non-ADHD controls were given a visual search word-matching task to assess impulsive responding. An analysis of covariance showed that ADHD children on methylphenidate made fewer impulsive errors than ADHD children on placebo. The control group made fewer impulsive errors than the ADHD children in the placebo condition, but the performance of the ADHD children on medication approximated the performance of the children without ADHD. These preliminary findings suggest that the word-matching task may be a useful tool for assessing impulsive responding and determining the benefits of stimulant medication on impulsivity. PMID- 8505480 TI - Intrauterine-onset myoclonic encephalopathy associated with cerebral cortical dysgenesis. AB - The intrauterine onset of convulsive syndromes has been documented only rarely, and previous reports have lacked detailed neuropathologic description. This report details a case of severe, intractable myoclonic encephalopathy, which, on the basis of severely abnormal paroxysmal fetal movement patterns confirmed by antenatal ultrasound, appears to have been of antenatal onset. The infant suffered an early demise and at autopsy showed features of a severe brain dysgenesis with polymicrogyria and superadded encephaloclastic features. Despite an extensive evaluation, the etiology of this condition remains elusive in our case. This case demonstrates that closer analysis of the qualitative features of fetal movements by, for instance, real-time ultrasound could aid in the antenatal diagnosis of neurologic, particularly convulsive, syndromes. PMID- 8505481 TI - Pediatric AIDS: a longitudinal comparative MRI and CT brain imaging study. AB - Fourteen consecutive children with acquired immune deficiency syndrome (AIDS) (age range, 4 months to 11 years; median 4 years) were studied prospectively comparing nonenhanced cranial magnetic resonance imaging (MRI) and computed tomographic (CT) scans. MRI and CT were performed twice: at time of entry into protocol and again at 1 year. In addition, sequential neurologic (every 2 months) and neuropsychological examinations (every 6 months) were performed. At entry, 12 children had abnormal neurologic examinations; of these, 10 had developmental delay; two children were normal by developmental history and neurologic examination. Five children performed in the normal range on a standardized neuropsychological test, whereas nine children showed significant delays in verbal or motor/perceptual development. Following 1 year of study, four children had normal and six had abnormal neurologic examinations (six stable and four improved). Neuropsychological examinations were normal in five children and abnormal in five (seven stable, one improved, and two deteriorated). At entry, the following neuroradiographic abnormalities were seen: brain parenchymal volume loss (eight, MR = CT), cervical lymphatic enlargement (four, MR = CT), striatal thalamic calcification (one, CT > MR), delayed myelination (one, MR > CT), and focal white-matter lesions (one, MR > CT). At 1 year the following neuroradiographic changes were seen: brain parenchymal volume loss (10, MR = CT; two improved, eight stable); cervical lymphatic enlargement (one, MR = CT; three improved, one stable), striatal-thalamic calcification (one, CT > MR; one new), and focal white-matter lesions (one, MR > CT; one stable).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505482 TI - Number 20 ring chromosome: a case with complete seizure control. PMID- 8505483 TI - Recurrent torticollis as a presentation of moyamoya disease. PMID- 8505484 TI - Brain imaging for absence seizures. PMID- 8505485 TI - Evolution of thrombosis of the vein of Galen in sickle cell disease. PMID- 8505486 TI - Are gastrointestinal disorders in the elderly important? AB - Gastrointestinal (GI) disease in the elderly has evoked little interest in GI clinicians and researchers, yet causes major disability. The clinical care of the bed-bound nursing home resident is greatly complicated by swallowing difficulties and fecal incontinence, but the gastroenterologist has little to offer. Peptic ulcers now are found in the elderly, where 90% of deaths occur. Research is beginning to clarify how the susceptibility to peptic ulcer disease may increase with age. Gastroenterologists are uncertain whether or when malabsorption may contribute to malnutrition in older subjects. Novel malabsorptive disorders, such as bacterial overgrowth without a structural cause, may result in nutritional disorders. Overall, physicians tend to reduce drug dosages and therefore undertreat the elderly: evidence suggests that little reduction in GI drug dosage is needed because of age alone. Gastrointestinal disturbances in the elderly require the attention and acumen of clinical gastroenterologists. PMID- 8505487 TI - Gastrocolic fistula. A review of 15 cases and an update of the literature. AB - Gastrocolic fistulas are not common. We review the 10-year experience in our center of 15 cases that emphasize the changing pattern of this disease. The female-to-male ratio was 2:1, with a mean age of 55. Even though we are affiliated with the regional cancer center, the commonest cause of a fistula was benign gastric ulceration. Sixty percent of those with peptic ulcer and a fistula had not had previous gastric surgery. Barium enema was the most accurate investigation, showing the fistula in 10 of 10. Barium meal showed it in seven of eight, and the fistula was seen in seven of 10 patients who had endoscopy. Eleven patients were operated on, and only one was treated "medically." Three deaths occurred, two from advanced carcinoma and one from myocardial infarction. PMID- 8505489 TI - Cholesterol crystal appearance time of gallbladder bile in middle-aged women. AB - The aim of our study was to examine the hypothesis that the cholesterol nucleation time of gallbladder bile might be rapid in women in their fourth and fifth decades, which increases their risk of cholesterol gallstones. Fifty-four gallbladder bile samples were collected from gallstone-free patients and patients with cholesterol gallstones in a functioning gallbladder. We examined the relations of nucleation time to age and sex in each group. The nucleation time of gallbladder bile tended to be prolonged with age, but there was no correlation between nucleation time and age in each group. Cholesterol nucleation time was not significantly different between age-matched females and males in each group, nor was it faster in middle-aged females than in older females. Thus, nucleation time was not rapid in middle-aged females even in the gallstone-free group. These results indicate that cholesterol nucleation time is not significantly influenced by either sex or age, and cannot therefore account for the higher frequency of cholesterol gallstone disease in females in the fourth and fifth decades. PMID- 8505488 TI - Clostridium difficile diarrhea in patients with AIDS versus non-AIDS controls. Methods of treatment and clinical response to treatment. AB - We reviewed the hospital charts of 17 patients with AIDS and Clostridium difficile diarrhea to determine antibiotic use before C. difficile infection, methods of treatment for C. difficile diarrhea, and response of diarrhea to treatment. Left shift and total white blood cell count before and after treatment for C. difficile were also determined. Non-HIV-infected patients with C. difficile diarrhea served as controls. In the patients with AIDS, resolution of diarrhea was noted in 15 (88%) patients. In 25 (76%) control patients, diarrhea resolved with treatment. The patients with AIDS also had a significant decrease (p < 0.05) in left shift in white blood cell count with treatment; the controls did not. Our study therefore suggests that C. difficile diarrhea is at least as likely to resolve with antibiotic therapy in patients with AIDS as it is in those with the non-AIDS-related disorder. We also found that patients with AIDS and C. difficile diarrhea are more likely than patients without AIDS to have a decreased left shift in white blood cell count after antibiotic therapy. PMID- 8505490 TI - Survival after combined modality therapy for pancreatic cancer. AB - Twenty consecutive patients with unresectable, locally advanced pancreatic cancer were treated with split courses of radiotherapy (RT) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil, continuous infusion, streptozotocin, and cisplatin. A separate, retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers, all of which were successfully resected. The survival rate of the two groups were similar over the first 2 years, although it initially favored the unresectable group. This pattern of survival among patients treated with combined modality therapy provides a basis for new studies. At the two clinical extremes, these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors. PMID- 8505491 TI - Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy. AB - Although venesection therapy is well established for the initial depletion of iron stores in hereditary hemochromatosis, the frequency of subsequent therapy has not been clearly defined. In this study, 21 homozygotes (16 male, five female; mean age of 58, with a range of 26 to 77 years) who had completed initial venesection therapy were followed without further venesections for a mean of 4.0 years (range of 1 to 10.4 years) with iron reaccumulation assessed by annual serum ferritin concentration. Over the follow-up period, the mean rise in serum ferritin was 99 (micrograms/l)/year (range of 1.2 to 241 micrograms/l). The mean interval for the ferritin to become elevated above the normal range in 10 patients was 3.8 years. Eleven of 21 patients required no further venesection therapy over the follow-up interval. There was no significant correlation between the annual rate of ferritin increase and the age or amount of iron removed by prior venesections. These data demonstrate that monitoring body iron stores annually and the selective use of venesections if iron stores reaccumulate is a safe alternative to lifelong venesections every 2-4 months. Many homozygotes will not require reinitiation of venesection therapy for > 4 years. Annual monitoring of body iron stores with reinstitution of weekly venesection when the serum ferritin exceeds the upper limit of normal was a safe alternative to long-term maintenance venesection. PMID- 8505492 TI - Stress and personality in patients with chronic peptic ulcer. AB - The concept that stress and personality are associated with ulcer is widely held by lay persons and to some extent by the medical community. By means of epidemiological techniques and more precise terminology, the role of psychosomatic factors in ulcer disease has been more clearly defined. Regarding acute stress, the number of events experienced and the change and distress they are purported to produce has been found to be similar in ulcer patients and their controls matched on age, sex, and social class. However, chronic difficulties, i.e., events or circumstances that have persisted for > or = 6 months, are twice as common in duodenal ulcer patients as in controls. Events, either acute or chronic, are more strongly associated with duodenal ulcer if they contain a component involving personal threat or goal frustration. Associations that have been found between acute or chronic stress and duodenal ulcer have been relatively weak, with odds ratios of 2 to 3. For some patients, it is possible that depression and social incongruity may have played some role in initiating ulcer disease. Personality studies have shown that ulcer patients are more neurotic than controls, but the difference is small and there is no evidence to indicate an ulcer personality. As regards both stress and personality, gastric ulcer patients do not differ from duodenal ulcer patients. PMID- 8505493 TI - Misoprostol healed a benign nonsteroidal antiinflammatory drug-induced gastric ulcer in a patient with pentagastrin-fast achlorhydria. AB - A patient with rheumatoid arthritis, who also had documented achlorhydria, first had the diagnosis of an antral ulcer made by barium meal in 1980. She did well taking cimetidine intermittently after that, along with various nonsteroidal antiinflammatory drugs (NSAIDs). In 1988, a shallow antral ulcer was found, but the patient did not respond to H2 blockade or to sucralfate. At that time misoprostol therapy was prescribed. Despite the continued use of NSAIDs, the ulcer healed. It has remained healed for the past 3 years. PMID- 8505494 TI - Miliary Crohn's disease: early or different? AB - We describe what we take to be the eighth case of miliary Crohn's disease since 1967 with a view to the possibility that miliary Crohn's disease is a disease different from Crohn's disease, and not just an early stage. Miliary Crohn's disease might be a different disease because (a) miliary tubercles are seen so rarely on the serosal surface of the bowel, (b) the 100% chance of finding crowded, typical granulomas in the bowel wall, and (c) the anatomic distribution of the lesion. PMID- 8505495 TI - Postcholecystectomy diarrhea from villous atrophy of the terminal ileum. AB - We report a 60-year-old man with intermittent diarrhea for 15 years which was worsened by cholecystectomy. The results of routine laboratory tests, x-ray studies of the gut, and endoscopy were normal. Fecal fat excretion was normal, but total bile acid excretion was increased in the alkaline feces. The retention of 75SeHCAT was low. Jejunal mucosal biopsy showed normal mucosa. Ileal biopsy was performed at ileoscopy some 10 to 15 cm proximal to the ileocecal valve. Scanning-electron and light microscopy showed a transitional zone between villous atrophy in the distal and normal mucosa in the proximal part of the biopsy specimen. The response of diarrhea to cholestyramine treatment was unequivocal, suggesting bile acid malabsorption. The increased enterohepatic cycling of bile acids after cholecystectomy may be responsible for a decrease in their ileal uptake. Very often, as in our patient, the diarrhea precedes cholecystectomy and is considerably increased by it. Cholecystectomy may unmask a previously unrecognized bile acid transport defect. In our patient, this defect might have been caused by the villous atrophy of the terminal ileum. PMID- 8505496 TI - Agenesis of the gallbladder in symptomatic adults. A case and review of the literature. AB - Agenesis of the gallbladder, with normal bile ducts, is a rare congenital condition occurring in 13 to 65 per 100,000 population, probably from failure of the gallbladder bud to develop or vacuolize in utero. Adults are usually asymptomatic. We report a 40-year-old woman with gallbladder agenesis, found at operation for presumed gallbladder disease. We review 44 similar cases: dyspepsia was the predominant symptom in 15 of 44 patients (34%); 24 of 44 (54%) had symptoms suggestive of biliary colic, and 12 of 44 (27%) had jaundice. Common duct stones were found in eight of 12 patients who were jaundiced, but not in any other. A familial tendency was reported in five series. Our patient and one other had another congenital anomaly. Ultrasound was performed on five patients: three had a small, shrunken gallbladder and in two the gallbladder was absent. Ultrasound may suggest the diagnosis if absence of the gallbladder is demonstrated in conjunction with another congenital anomaly. PMID- 8505497 TI - Transient focal hepatic defects related to sustained-release niacin. AB - Hepatotoxicity is a potential side effect of niacin therapy for hypercholesterolemia, ranging from mild aminotransferase elevation to fulminant hepatic failure. Although uncommon with plain forms, liver dysfunction has increasingly been associated with sustained-release preparations. This case illustrates transient focal liver defects seen on computed tomography with symptomatic elevation of liver-associated enzymes during treatment with sustained release niacin. The masses were not evident on radionuclide liver scan, suggesting focal fatty liver. After niacin was discontinued, these abnormalities resolved, and aminotransferases returned to normal. This is the first such reported case. PMID- 8505498 TI - Hereditary angioneurotic edema with severe hypovolemic shock. AB - Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients. PMID- 8505499 TI - Reactive lymphoid hyperplasia of the liver. AB - A patient with reactive lymphoid hyperplasia of the liver was symptom free and had no underlying disease except for diabetes mellitus. The hepatic tumor was found by ultrasound examination at routine checkup. The preoperative diagnosis of the tumor was unsuccessful despite various radiological examinations. Histological examination of the resected tumor showed that it was composed of benign-appearing lymphocytic proliferations forming lymphoid follicles that included numerous germinal centers. The germinal center was mainly composed of B cell marker, L26-positive lymphocytes, but a few T cells were also found. Lymphocytes surrounding germinal centers were mainly T-cell marker, UCHL1 positive T-cells, and a small number of B cells. The B cells in the lymphoid follicles were stained for both kappa and lambda light chains at equal frequency, indicating polyclonal and benign nature. A diagnosis of reactive lymphoid hyperplasia of the liver seems justified. PMID- 8505500 TI - Diagnostic workup strategies for patients with HIV-related chronic diarrhea. What is the end result? AB - The intensity of diagnostic workup of patients with human immunodeficiency virus (HIV)-related chronic diarrhea is controversial. In the ideal setting in which an enteric pathogen is detected with minimal evaluation (stool tests) and in which specific treatment clears the diarrhea, eradicates the pathogen, and improves the patient's quality of life, the need for diagnostic workup is clear. However, problems frequently occur in the evaluation and treatment of patients that preclude such a straightforward approach. They are (a) failure to detect enteric pathogens; (b) detection of organisms of uncertain significance; (c) lack of effective treatment; (d) the presence of a severe coexisting illness that is the major determinant of the patient's outcome; and (e) lack of evidence that detecting enteric pathogens leads to improvement in broad patient outcomes, such as quality of life. I discuss these problems and examine the two opposing diagnostic workup strategies--minimal and intensive evaluation--that have been advocated. My main conclusion is that both approaches fall short, and that clinicians lack the information needed to guide clinical decision making. I urge investigators to analyze the full effects of alternative diagnostic interventions on broad patient outcomes so that clinical guidelines can be developed to assist the evaluation of patients. PMID- 8505501 TI - Endoscopic characterization of idiopathic esophageal ulceration associated with human immunodeficiency virus infection. AB - Idiopathic esophageal ulcerations (IEUs) associated with human immunodeficiency virus (HIV) infection are now recognized as an important cause of esophageal disease in this population. Limited radiographic and endoscopic reports have almost uniformly described these lesions as solitary and giant. Over a 28-month period, we identified 68 IEUs endoscopically in 23 patients. Most patients had long-standing HIV infection and a low CD4(+) lymphocyte count. Multiple ulcers were identified in 57% of endoscopies. Giant ulcers were seen in one-third, with 37% < or = 1 cm in greatest dimension. Most of the lesions were in the mild- to distal esophagus. The ulcers were characterized as either shallow or intermediate in depth in 53%, with a deep ulcer in 7%. A "heaped-up" appearance of the ulcer was identified in 40%. An esophageal mucosal bridge(s) was seen in two patients. In contrast to previous reports, IEUs are variable endoscopically in number, size, and appearance. Given this lack of uniformity in appearance, which may mimic other causes of esophageal ulceration, all HIV-infected patients with an esophageal ulceration should undergo endoscopy with biopsy to obtain a definitive diagnosis. PMID- 8505503 TI - Pancreatic lymphoma. PMID- 8505502 TI - Helicobacter pylori infection in Greece in healthy people and in patients with peptic ulcer and with dyspepsia without ulcer. PMID- 8505504 TI - Elective laparoscopic cholecystectomy in a patient with hemophilia. PMID- 8505505 TI - Does a single granuloma warrant a diagnosis of idiopathic granulomatous gastritis? PMID- 8505506 TI - Asymptomatic primary sclerosing cholangitis in association with inflammatory bowel disease. PMID- 8505507 TI - Regression of a great abdominal desmoid tumor by interferon alpha. PMID- 8505508 TI - Evidence of neurofibromatosis and chronic myelogenous leukemia in a liver biopsy specimen. PMID- 8505509 TI - Pyloric stenosis caused by metastases from ovarian carcinoma. PMID- 8505510 TI - Aspirin-induced cholestatic hepatitis. PMID- 8505511 TI - Small bowel sarcoma presenting as a diverticular abscess. PMID- 8505512 TI - Helicobacter halitosis. PMID- 8505513 TI - Early defibrillation program: problems encountered in a rural/suburban EMS system. AB - Many studies have shown improved survival of cardiac arrest patients by the use of early defibrillation (EMT-D) in the field. This prospective study was the first in Pennsylvania and was undertaken to determine if an EMT-D program would be successful in our suburban/rural setting. One hundred two EMTs were trained to use a semi-automatic defibrillator and data were collected over 16 months. There were 96 cardiac arrests, with only 33 patients (34%) presenting with initially treatable dysrhythmias--ventricular fibrillation (VF) or tachycardia (VT). Twenty three patients (24%) were admitted to the hospital; survival to hospital discharge occurred in only 5 patients (5.2%). Survival to hospital admission was higher among VF/VT presenting rhythms (36%) than for those with other rhythms (17%, P = 0.07), but survival to discharge among VF/VT rhythms (9%) was not statistically different from other rhythms (3%, P = 0.45). Among VF/VT patients, survival to discharge was correlated with shorter call to first defibrillation intervals. Mean call to response interval was longer than in other reported studies (7.2 +/- 4.3 minutes). In addition, there was a high drop-out rate of EMT participants, no central/uniform early access system (that is, 911), and a lower rate of CPR than reported in other studies. It is concluded that introduction of an EMT-D program without careful analysis of systems response factors will not lead to the improved cardiac arrest survival percentages that have previously been reported. PMID- 8505514 TI - System care improves trauma outcome: patient care errors dominate reduced preventable death rate. AB - A review of 452 trauma deaths in Hillsborough County, Florida, in 1984 documented that 23% of non-CNS trauma deaths were preventable and occurred because of inadequate resuscitation or delay in proper surgical care. In late 1988 Hillsborough County organized a County Trauma Agency (HCTA) to coordinate trauma care among prehospital providers and state-designated trauma centers. The purpose of this study was to review county trauma deaths after the inception of the HCTA to determine the frequency of preventable deaths. RESULTS: 504 trauma deaths occurring between October 1989 and April 1991 were reviewed. Through committee review, 10 deaths were deemed preventable; 2 occurred outside the trauma system. Of the 10 deaths, 5 preventable deaths occurred late in severely injured patients. CONCLUSION: The preventable death rate has decreased to 7.0% with system care. The causes of preventable deaths have changed from delayed or inadequate intervention to postoperative care errors. PMID- 8505515 TI - Abdominal wall and stomach perforation following accidental electrocution with high tension wire: a unique case. AB - The usual form of direct gastrointestinal injury following high-tension electric injury is widespread necrosis of the colon or the small intestine. It usually occurs in combination with extensive electric burns of the overlying abdominal wall. We report a case of immediate post-electrocution abdominal wall and stomach perforation following high tension electric injury. The total absence of coagulation necrosis of the stomach or other portions of the gastrointestinal tract and the absence of burns of the abdominal wall were other unique features of the case reported. The patient was successfully treated. PMID- 8505516 TI - Paraesophageal hernia in an elderly woman. AB - We present a case of an elderly woman with a paraesophageal hernia. This is an uncommon type of hiatal hernia and may result in a surgical emergency if incarceration, obstruction, or strangulation is present. Our patient presented with a clinical picture consistent with myocardial ischemia. We discuss the differential diagnosis, the pathophysiology, complications, diagnostic studies, and treatment of this disease. PMID- 8505517 TI - Primary Vibrio vulnificus septicemia. AB - We present a fatal case of primary Vibrio vulnificus septicemia in a patient with chronic alcoholic liver disease. The patient had recently consumed raw seafood. The epidemiology and clinical presentation of Vibrio vulnificus infection is discussed. Preventive, early empiric therapy, and aggressive search for this organism in patients at risk is stressed. PMID- 8505518 TI - An unusual case of intermittent upper airway obstruction. AB - Thyroglossal duct cyst is an unusual cause of intermittent upper airway obstruction and rarely produces obstructive symptoms in adults. Previous reports discuss airway obstruction in small children and infants and point out the complications of such cysts, including thyroid carcinoma, adenoma, thyroiditis, and thyrotoxicosis, as well as inflammation and infection. Diagnosis should be considered in all cases of midline neck masses and is usually aided by diagnostic imaging. Treatment may involve airway maintenance and surgical excision of the cyst and its entire tract. PMID- 8505519 TI - Hanging arm method for reduction of dislocated elbow. AB - This paper describes two patients with posterior dislocation of the elbow in whom the dislocation was reduced atraumatically by a modified hanging arm method not previously described. Further research is recommended to evaluate this method. PMID- 8505520 TI - Congenital diaphragmatic hernia--Morgagni type. AB - A Morgagni hernia was discovered in a 4-year-old girl who presented with fever, cough, and abdominal pain. The case report and a discussion of this unusual entity are presented. PMID- 8505521 TI - Bilateral hypoglossal nerve palsies following head injury. AB - Bilateral hypoglossal nerve palsies following head injury are very rare, with only two cases previously being reported. We present the case of an 11-year-old boy who developed this disorder after being struck by a car, and discuss the mechanism of injury, which is most likely traction on the hypoglossal nerve. PMID- 8505522 TI - The HELLP syndrome: case report and review of the literature. AB - A pregnant patient with a chief complaint of chest pain was found to have many characteristic findings of the HELLP syndrome. A number of pregnancy-related conditions have in common various degrees of hypertension, proteinuria, edema, hemolysis, elevated liver enzymes, and low platelets. Emergency physicians should search for clinical and laboratory signs of these conditions when evaluating ill pregnant patients. PMID- 8505523 TI - Electric shock in pregnancy. AB - Emergency physicians need to be alert to the potential effects of electric shock in pregnancy. A review of all case reports in the English language literature of pregnant women exposed to electric shock was performed. Information on voltage, gestation, injury-to-delivery interval, and outcome was collected. There were 15 victims of electric shock in pregnancy. Fetal mortality (N = 11) was 73% and there was only one normal pregnancy following electric shock. The fetus is much less resistant to electric shock than the mother. Any woman who suffers from an electric shock in pregnancy, however minor, requires prompt fetal monitoring and careful obstetric supervision. PMID- 8505524 TI - CT detection of occult pneumothorax in multiple trauma patients. AB - Chest injuries are the cause of death in 25% of trauma fatalities, and a major contributing factor in an additional 50%. Pneumothorax, the second most common chest injury, may often be initially overlooked. Administration of anesthesia and mechanical ventilation may produce enlargement of a pneumothorax and clinical deterioration. We reviewed 90 trauma patients who had been admitted with a diagnosis of pneumothorax or who had developed pneumothoraces after hospital admission. In 35 cases (38.8%), initial supine chest x-ray study failed to detect a pneumothorax, and the diagnosis was made on CT scan of the chest or abdomen performed within 2 hours of admission. In 15 of these cases (42.8%), identification of the pneumothorax on CT scan resulted in alterations in management, including chest tube placement in 10 patients and intensified monitoring in 5 patients. Failure to identify pneumothoraces in trauma patients may lead to deterioration and significant complications in patients requiring anesthesia or mechanical ventilation. CT scan may facilitate identification in these cases. PMID- 8505525 TI - Biomechanical performance of microsurgical spatula needles for the repair of nail bed injuries. AB - The purpose of this study was to determine the mechanical performance of microsurgical spatula needles for repair of nail bed injuries. Standard biomechanical tests have been devised to evaluate the performance of microsurgical spatula needles. Two comparable groups of microsurgical spatula needles were selected from two different manufacturers for these biomechanical studies. The results of this testing demonstrated that needle point geometry and needle composition were important determinants of needle performance. When needles of comparable size were evaluated, the biomechanical performance of the CS160-8 spatula needle (Ethicon, Inc., Somerville, NJ) was superior to the C-5 spatula needles (Alcon, Inc., Fort Worth, TX). While the development of these biomechanical tests has allowed the evaluation of these microsurgical spatula needles, these same tests can be used to assess the performance of new microsurgical spatula needles. PMID- 8505526 TI - Inappropriate use of passive safety features in automobiles. PMID- 8505527 TI - Objectives to direct the training of emergency medicine residents in pediatric emergency medicine. AB - This article outlines the objectives for a resident rotation on a pediatric emergency medicine service that is geographically separate from adult-oriented facilities. In this setting, pediatric emergency department care is considered an off service. However, these objectives incorporate key pediatric knowledge and techniques in a practical format for emergency medicine trainees who have no separate pediatric emergency department experience. The content of the pediatric emergency department educational exposure can be attained in a concentrated 2 month exposure at a pediatric facility or extracted throughout the course of multiple pediatric encounters at a general emergency department. These objectives are a part of a continuing series on the goals and objectives to direct emergency medicine resident training on off-service rotations. PMID- 8505528 TI - IRIS: an experimental multimedia workstation linking the departments of emergency medicine and radiological sciences. AB - An experimental version of a multimedia medical communication system called IRIS (Integrated Radiological Information System) operated between the Department of Emergency Medicine and the Department of Radiological Sciences at the Ottawa Civic Hospital for 7 weeks during April and May 1989. IRIS is being developed to enhance communication between clinicians and radiology consultants to improve diagnosis and reporting. IRIS supports the capture and distribution of digitized x-ray images and voice reports in the form of "electronic" patient folders that can be accessed at physician workstations throughout the hospital. It also supports on-line consultation between the radiologist and clinician through synchronized workstation operation. Each workstation has 1) a high resolution image screen to display documents and x-ray images; 2) a control screen to access patient folders; 3) a hands-free telephone to dictate, play back reports, and enable realtime consultation between physicians. From an emergency physician's (EP) perspective, such an involved system must allow the viewing and manipulation of images in order to reach diagnostic conclusions and support efficient interchange between the clinician and the consultant radiologist, yet be easy to learn and use without disruption of clinical services. After a briefing session, the trial took place and analogue and digital images were compared. An observer assistant recorded how EPs used the system and was available to assist the EP. After the trial, six EPs participated in an extensive debriefing interview in order to evaluate the system. Overall, the system was found to be easy to learn and to use, and there was a clear benefit to the full consultation report and the ability to directly consult with the radiologist located at a remote station. PMID- 8505529 TI - A critique and synthesis of biological essentialism and social constructionist views of sexuality and gender. AB - To say that a person is homosexual is a statement about an individual in a particular social context and at a particular point in that person's life. Homosexuality is an aspect of sexual and gender expression that profoundly reflects contemporary social and cultural values. The essay is critical of both biological essentialist and social constructionist views. Biological essentialism depicts a process in which biological influences precede cultural influences and set predetermined limits to the effects of culture. In effect, it submerges sexual preference, a human process, into sexual orientation, a biological mechanism. Social constructionism tends to depict the individual as an empty organism that is filled and shaped by culture and society and is devoid of consciousness and intention. An alternative view is proposed that views sexual and gender expression as a product of complementary biological, personal, and cultural influences. PMID- 8505530 TI - Gay fathers in straight marriages. AB - The author bases his conclusions about gay parenthood on anecdotal evidence gathered from about 100 gay German fathers. First he notes how the religious ethic that surrounds the nuclear family stands in the way of a father's awareness and expression of his homosexual desires. Like van der Geest, he reports that many women are attracted to gay men and proceed to marry them. After coming to realize that husbands' homosexual affairs are transitory and do not constitute a serious challenge to marital and family bonds, a few couples have been able to preserve their marriages. In most cases the marriages collapse under the combined pressures of wife and gay lover both claiming exclusive proprietorship: "the 'love triangle' can rarely be closed." The author laments the existence of all male gay communities that ignore the existence of females and force gay husbands and fathers to choose against marriage and parenthood. PMID- 8505531 TI - Homosexuality and marriage. AB - Discusses the problems of heterosexual partnership, when one of the partners engages in a homosexual relation. Notes the biblical data on homosexuality and fidelity. Draws attention to the concept of the New Couple as a possible solution. PMID- 8505532 TI - Can seduction make straight men gay? AB - The article raises the question of changing sexual preference: Can a man whose past sexual practice has been almost exclusively heterosexual change his practice to homosexual after being seduced by another man? To those who believe that homosexual preference is homosexual orientation, an innate biological predisposition, the answer is a resounding "no." Contrary to this response, the author presents three cases in which the men switch from heterosexual to homosexual relationships (exclusively in two cases) by means of a sexual encounter initiated by another man. The author credits part of the change to the gay liberation movement which rescued homosexual desire from the hidden, forbidden, and shameful. The evidence that these men experienced a genuine change in sexual preference, shows that life-long, exclusive homosexuality, as articulated by gay rhetoric, is more a statement about the culture in which it occurs than the "essence" of homosexuality. The author concludes that putting the question of "What do I like?" before the question of "Who am I?" would allow more sexual freedom for those interested in crossing the line that divides sexual preferences. PMID- 8505533 TI - The Freudian construction of sexuality: the gay foundations of heterosexuality and straight homophobia. AB - In developing his theory of male sexual preference, Freud asserted that heterosexual as well as homosexual preferences required explanation, that neither could be assumed to be innate. His theory of the oedipal complex, however, held that the heterosexual outcome was the "normal" resolution, while the homosexual outcome represented arrested sexual development. In the normal resolution the boy identifies as a male with the father, gives up the mother as a love object, and later substitutes another woman of his choice for the mother. The author of the following article, following the theorizing of Laplanche, claims that there is an unavoidable homosexual component or residue in the heterosexual resolution which is implicit in Freudian theory. In the resolution of the complex the boy has the choice of both parents as love objects or as persons with whom to identify. In the heterosexual resolution the boy identifies with the father as a rival for the mother's affection. But love and identification are not entirely discrete processes. The identification with the father involves love for the father. The heterosexual resolution of the oedipal conflict is bought at the price of the homosexual resolution which, however, is not completely surrendered. The homophobia of heterosexual males, the author asserts, is the result of the remnants of homosexuality in the heterosexual resolution of the oedipal conflict. PMID- 8505534 TI - Mati-ism and black lesbianism: two idealtypical expressions of female homosexuality in black communities of the Diaspora. AB - There are different ways in which black women in the Diaspora have given expression to their erotic fascination with other women. In this article two idealtypical expressions of black female homosexuality and the outlines of their underlying cosmologies are sketched: mati-ism and black lesbianism. Mati (or matisma) is the Sranan Tongo word for women who have sexual relations with other women, but who typically also will have had or still have relationships with men, simultaneously. More often than not they will also have children. While both types can only be understood via a constructionist view of homosexuality, the institution of mati-ism will be shown to have retained more Afrocentric, working class elements, while black lesbianism has more middle class, Eurocentric features. PMID- 8505535 TI - Homosexuality and police terror in Turkey. AB - Being a way of sexual living as old as human history, homosexuality occupies an interesting place in the life of the Turkish people of the Republic of Turkey. This has been so since the days of the glorious Ottoman Empire. In the year 1987, instead of investigating the roots of homosexuality, the pressing need has become to present a particular view of homosexuality in Turkey today. To be more specific, there is a need to explain the problems of Turkish homosexuals and suggest certain vital solutions. Our country is constantly endeavoring to become "westernized" and it is claimed that steps are being taken toward that modernization. Despite this fact, homosexuals are confronted with such great problems that it is not difficult to justify those who say that there is no democracy in Turkey. I will try to explain these problems with documentary evidence and without exaggeration. In doing so, I shall make use of new material in my book, published under the title of Homosexuality in Turkey: Yesterday, Today. Beginning in March of 1986, we compiled a list of the attitudes of the police toward gays, involving pressure and cruelty that can be qualified as torture. Despite this situation, instead of being more democratic and humane, in April 1987 the police force employed terror tactics against homosexuals in Istanbul. This was "the straw that broke the camel's back." Soon after this act of oppression, 18 gays, acting on our suggestions, sued the police for the first time. They then submitted a petition to the Attorney-General and later launched a hunger strike in Taksim Square. These represent movements of importance in the political history of Turkey. From now on homosexuals, too, will have the right to speak out in political affairs. PMID- 8505536 TI - In Nicaragua: homosexuality without a gay world. AB - This paper addresses the social construction of homosexual relations among men in Nicaragua in the late 1980s. The political economy of a nation, subjected to a devastating war by the United States, created conditions where sexual relations among men have not become organized into a gay world which would be familiar to North Americans and Europeans. Rather, homosexually-inclined men remain fully integrated in family and neighborhood life where they are often "known about" but not "recognized," a condition which dissolves separateness but also suppresses the development of a gay culture beyond the bounds of heterosexist expectations. PMID- 8505537 TI - Invertidos sexuales, tortilleras, and maricas machos: the construction of homosexuality in Buenos Aires, Argentina, 1900-1950. AB - The author discusses Argentinean construction of homosexuality from 1900 to 1950 in the context of the raging debate of the essentialists versus social constructionists. The history of sexual inverts is discussed with reference to early sexologists. After a broad exploration of sexual inversion, the author turns to the Argentinean doctors who distinguish between acquired and congenital inverts. There was much resistance to the medical and legal establishments as there were autobiographies written by inverts, who subverted the medical views of the day. Finally, Bao concludes that there was, indeed, an Argentine construction of homosexuality, and that there were similarities between Buenos Aires and other large European cities. It is also noted that at the beginning of the twentieth century, there was a developed Argentine subculture of inverts who had meeting places, fashion, sexual tastes, and customs. PMID- 8505538 TI - The mineshaft: a retrospective ethnography. AB - The Mineshaft, a male sex club, is described from the patron's perspective, in retrospect, and in the context of gay male urban life in circa-1980 North America. It is suggested that the Mineshaft functioned to provide, on a for profit basis, a relatively safe environment for liminal erotic behaviors, and did so in response to a variety of sociocultural conditions. The latter include the lack of institutionalized anticipatory socialization for intramale sexual relations, and the tension between S&M and non-S&M gay male styles. The Mineshaft occupied marginal niches in terms of its physical location, its hours of operation, and its legal status. Access was ritualized, social structure was simplified, social control was informal but adequate. The setting was amendable to a wide range of fantasy, eroticization and erotic role playing. PMID- 8505539 TI - Essentialism, which essentialism? Some implications of reproductive and genetic techno-science. AB - New technologies, such as genetic screening, artificial insemination, in vitro fertilization, and pre-natal diagnosis, have given new meaning to human reproduction. Such innovations make clear that marriage, procreation, and the biological family are not the sole "natural" means of perpetuating the human race. One would have hoped that these inventions would eventually have raised in public regard the gay/lesbian family to the same level as heterosexuality and the biological family. Franklin shows, however, that the old heterosexual essentialism is preserved by government restricting the use of the new technologies to two-parent families consisting of both mother and father. What should have resulted in the erosion of heterosexual privilege has, instead, led to its reinforcement. Franklin draws a parallel with the AIDS epidemic which could have been the opportunity to spread knowledge and acceptance of varied forms of sexuality but has instead been used to shore up a traditional sexual morality and a renewed vilification of homosexuality. PMID- 8505540 TI - Childhood cross-gender behavior and adult homosexuality: the resurgence of biological models of sexuality. AB - Research on the causes of homosexuality frequently treat it as a matter of disturbed gender identity and/or gender role. Recently, attempts have been made to link cross-gender behavior among boys with adult homosexuality. Often this research presumes a common biological determinant to both the childhood behavior patterns and homosexuality in adulthood. Authors have described such childhood cross-gender behavior in boys as part of a "prehomosexual" configuration. This paper argues that the research to date suffers from (1) a failure to differentiate such concepts as gender identity, gender role and sexual orientation, (2) a reliance upon potentially inappropriate dichotomies in describing such concepts, (3) problematic interpretations of research that makes few distinctions between human sexual behavior and sexual behavior among rodents, and (4) the contradictions implicit in seeking simple biological determinants of constructs (such as cross-gender behavior) that are culturally determined. The author argues that any potential biological factors contributing to sexual orientation must be mediated by a complex sequence of experiences and psychosocial factors. Therefore, the essentialists' search for a simple congruence between physiological or biological traits and homosexuality may be expected to fail. PMID- 8505541 TI - Reproductive strategies and gender construction: an evolutionary view of homosexualities. AB - In this chapter the author addresses the following question: Can the historical occurrence of various forms of homosexuality and bisexuality be explained as part of the management of reproduction in response to environmental conditions? She believes that explanations for the occurrence and forms of homosexuality appealing to genetics are biologically indefensible and historically inadequate. However, Darwinian behavioral theory, and specifically that subset termed life history theory, provides an explanatory framework. An individual's life course consists of behaviors coerced by parents and chosen by the individual in response to environmental conditions, forming a coherent reproductive strategy. In the process, alternate male and female genders, such as cadet sons, spinsters, and religious celibates are explained and the normative male bisexuality of Classical Athens and modern Mediterranean/Latin societies is elucidated. The rise of modern homosexuality in industrial nations results from the demographic transition to low mortality and low fertility, relaxing the reproductive management of children by parents and permitting a greater role for temperament in individual sexual and gender choices. PMID- 8505542 TI - The social construction of homosexuals in the nineteenth century: the shift from the sin to the influence of medicine on criminalizing sodomy in Germany. AB - Psychiatry and forensic medicine developed a medical model of deviance locating the source of homosexual behavior within the individual and postulating a physiological condition that is assumed to cause the deviant behavior. The shift in deviance designation from sexually sinful behavior to sexually unhealthy individuals affected social control and sexual criminal law in Germany during the second half of the 19th century. This research project analyzes the process of legislation and the application of sexual law in the German Reich during the period between 1860 and 1920. PMID- 8505543 TI - The construction of identities as a means of survival: case of gay and lesbian teachers. AB - The article, at its most general level, questions the requirement for "coming out" in public, which the author sees as the central demand of gay liberation ideology upon its adherents. Using research on teachers, the article shows that the political demand that teachers come out professionally ignores the central professional and political concerns of several teachers and their need for professional survival. In this study, teachers were found to have varying lifestyles. Coming out fitted the lifestyle only of those teachers who took on the role of crusaders for gay liberation. This role was often a secondary concern for women, who were more strongly identified as feminists than lesbians, and for men for whom homosexuality was not a major aspect of their lifestyle. The author suggests that more attention should be given to the homophobic conditions under which such teachers work than to the requirement that they all come out. PMID- 8505544 TI - Production of bi-specific monoclonal antibodies in a hollow-fibre bioreactor. AB - In the present study we have measured the feasibility of producing high amounts of bi-specific monoclonal antibodies (MAb) for therapeutic purposes using a hollow-fibre bioreactor. We have studied the isotype composition and functional capacity of an OKT3/OV-TL 3 quadroma (IgG2a/IgG1) and we have compared the production of bi-isotypic MAb in this system with tissue culture flasks or mouse ascites. Both culture supernatant and purified bi-isotypic MAb were able to enhance the cytolytic activity of a CD8+ T cell clone against ovarian tumour cell lines, demonstrating the presence of functional bi-isotypic MAb (bi-specific MAb). The total amount of immunoglobulin produced after 38 days was 375 mg. After purification by protein A affinity chromatography, 79 mg of bi-isotypic MAb (IgG1/IgG2a) was obtained. This amount of bi-isotypic MAb was similar to the amount obtained from ascitic fluid produced by 200 mice or 38 l of tissue culture flask supernatant. PMID- 8505545 TI - Detection of inhibition of HIV-1 protease activity by an enzyme-linked immunosorbent assay (ELISA). AB - An ELISA is described for the detection of HIV-1 protease activity using an immobilized gag-related polyprotein as substrate. Proteolytic activity was demonstrated with either bacterial lysates expressing HIV-1 protease or purified protease. No cleavage was observed with a protein preparation from control bacteria not expressing HIV-1 protease. Under these conditions the aspartyl-type protease inhibitor, pepstatin A, was found to inhibit HIV-1 protease cleavage by > 90% at a concentration of 0.1 mM. This assay may be a useful tool for the study of both synthetic and natural inhibitors of HIV-1 protease. PMID- 8505546 TI - Rapid generation of monoclonal antibody-secreting hybridomas against African horse sickness virus by in vitro immunization and the fusion/cloning technique. AB - Splenocytes from non-immune mice were stimulated in vitro using an equimolar mixture of factors from mixed lymphocyte reaction (MLR) and from phorbol-12 myristate 13-acetate (PMA) stimulated EL-4 cells, and concomitantly immunized with inactivated African horse sickness virus (AHSV) antigen serotype 4 or viral proteins 2 and 5 from AHSV serotype 9. Fusion with NSO myeloma cells was performed five days after primary or secondary stimulation/immunization. The record of hybridoma growth after a standard method of fusion, expansion of cells and subsequent cloning was compared with a fusion/cloning method in which cells were cloned within 2 to 3 days of the fusion event. Detection of antigen specific antibodies in the hybridoma culture supernatants was successful only with cells derived from primary stimulation/immunizations. Antibodies were detected using an indirect ELISA with the immunizing antigen coated on to the surface of the plates. Monoclonal hybridomas were isolated within 2 to 3 weeks using the fusion/cloning method, compared with the standard method, where it took 4 to 5 weeks. Although the total number of clones isolated from the fusion/cloning method was less than that obtained through the standard method, the yield of specific antibody-producing hybridomas as a percentage of the total picked was often more efficient with the fusion/cloning method. With respect to the immunoglobulin isotype produced, not all of the antibodies could be classified by the ELISA system used; 14% of anti-AHSV positive clones were identified as IgG secreting cells, 25% as IgM-secreting, 18% were cross-reacting with IgG and IgM, and 43% could not be classified. Similar results in all aspects of the work were obtained whether a crude infected cell extract or purified outer capsid polypeptides VP2/5, from serotype 4 and serotype 9 respectively, were used. PMID- 8505547 TI - Phage display as a rapid gene expression system: production of bioactive cytokine phage and generation of neutralizing monoclonal antibodies. AB - Proteins, such as hormones, enzymes, or antibody binding sites, can be expressed in an active conformation on the surface of filamentous bacteriophage. Although the phage display technology was originally developed for binding studies, we demonstrate here that this technique can rapidly provide cytokines for studies of biological activity and for raising neutralizing monoclonal antibodies. A phage M13-based cloning vector was constructed that facilitated the expression of human interleukin 3 (hIL-3) on the phage surface. The recombinant phage could stimulate the growth of the hIL-3 dependent cell line M-07, providing evidence for the display of hIL-3 in an active form. Injection of recombinant phage into mice provoked an immune response to hIL-3, and neutralizing monoclonal antibodies directed against native hIL-3 could be established from these mice with a high frequency. PMID- 8505548 TI - Mice ascites as a source of polyclonal and monoclonal antibodies. AB - A large quantity of polyclonal anti-ovalbumin antibodies was obtained from mice by a simple modification of the method described by Kurpisz et al. (1988). In addition, the cells from ascitic fluid were used to produce monoclonal antibodies. Egg ovalbumin hyperimmunized BALB/c mice were injected successively with pristane, antigen and a non-antibody secreting myeloma cell line: the production of ascitic fluid containing antiovalbumin antibody activity was observed after 10-25 days. Cells from ascitic fluid were harvested, washed and fused together with polyethylene glycol to produce monoclonal antibodies. Two fusions were performed and a large number of monoclonal anti-ovalbumin antibodies was obtained. This method is simple, reproducible, allows many fusions to be obtained from one mouse, and allows the use of ascitic B cells rather than the more, frequently used splenic B cells. PMID- 8505549 TI - The separation and identification by monoclonal antibodies of dog IgG fractions. AB - Four fractions of IgG from normal dog serum have been successfully isolated by gel filtration followed by protein A and protein G affinity chromatography using the fast protein liquid chromatography (FPLC) system. Protein A chromatography produced three peaks: peak 1 was fallthrough material consisting of components which did not bind to protein A, peak 2 consisted of bound material eluting at pH 6, and peak 3 contained bound material eluting at pH 3.5. The three peaks were then subjected individually to protein G affinity chromatography. Peak 1 from protein A chromatography produced a fallthrough peak followed by a weakly binding component which eluted at pH 8, and was called peak w. Peak 2 from protein A chromatography bound to protein G and eluted as a single peak at pH 3.8, and was called peak x. Peak 3 from protein A chromatography emerged as two separate peaks (y and z) off the protein G column; peak y bound and eluted at pH 4.1, and peak z bound weakly to protein G and emerged as a broad band at pH 8. Peaks w, x, y and z have been named gamma w, gamma x, gamma y and gamma z, respectively, and there purified IgG fractions were used to immunize mice for the preparation of monoclonal antibodies (McAbs). To date, two sets of McAbs have been produced: one which recognizes an epitope present in both gamma w and gamma z fractions and another set of McAbs which recognizes an epitope in the gamma x and gamma y fractions. PMID- 8505550 TI - Single and dual labelling of cytotoxic target cells. Comparison of three radioactive tracers, [35S]methionine, [75Se]selenomethionine, and chromium-51. AB - [75Se]selenomethionine (75SeM) has been shown to provide several advantages over Na(2)51CrO4 (51Cr) labelling of metabolizing target cells: high labelling efficiency and low spontaneous release of 75SeM-labelled target cells permit improved monitoring of cytotoxicity due to extended effector/target ratios in short- and long-term assays. Unfortunately, 75SeM will soon be difficult to obtain. Therefore we studied the suitability of [35S]methionine (35SM) as a substitute for 75SeM. Furthermore, we explored the potential of dual labelling of suspension target cells applying combinations of 35SM and 51Cr or 75SeM and 51Cr. 35SM is a suitable substitute for 75SeM retaining most of the advantages of 75SeM labelling. Although considerably higher labelling of cells is possible we obtained the most efficient labelling with 100-400 kBq/ml of 35SM or 75SeM resulting in a relatively high uptake (3-15 cpm/cell) and very low spontaneous release (1-2%/h) up to 24 h. This permits short- and long-term cytotoxic assays and the use of low numbers of target cells (1 x 10(3)) providing increased cytotoxic sensitivity with reduced amounts of effector cells. Suitable dual labelling of target cells with 35SM plus 51Cr or 75SeM plus 51Cr documented convincingly identical release kinetics for 35SM and 75SeM but partially discordant ones for 51Cr. Depending on the target cell used dual labelling permits discrimination and monitoring of different cytotoxic or release mechanisms in cellular cytotoxicity. PMID- 8505551 TI - Use of immunoplot analysis for the identification of immunodominant non-variant antigens of Trypanosoma brucei rhodesiense. AB - The application of the 'immunoplot' technique to the analysis of a complex series of immunoblots is described. A number of isolates of Trypanosoma brucei rhodesiense blood forms from Uganda, Kenya and Zambia were separated by SDS-PAGE under reducing and non-reducing conditions and transferred by immunoblotting onto nitrocellulose paper. The separated antigens from each isolate were then probed with sera from European and endemic controls, and a large panel of sera from confirmed trypanosomiasis patients. The resulting series of immunoblots was examined by the 'immunoplot' technique, which involves comparing frequencies of recognition of each band by the sera of controls and patients. A number of antigens of possible diagnostic interest were identified; a bad of 37/38 kDa was found to be recognised with high frequency (> 55%) by the sera of patients and virtually not at all by control sera under both reducing and non-reducing conditions. When this band was combined with one of the other frequently recognised bands, recognition by patient sera was raised to 92% (reduced) and 76% (non-reduced). This did not appear to be isolate-specific. The 'immunoplot' technique has potential for further development and wider use in immunoepidemiology and immunodiagnostic research. PMID- 8505552 TI - An MTT-based method for the in vivo quantification of myotoxic activity of snake venoms and its neutralization by antibodies. AB - The reduction of the tetrazolium compound MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-tetrazolium bromide) was used as the basis for the development of a simple method for the quantitative estimation of metabolically active skeletal muscle tissue remaining after in vivo venom-induced myonecrosis. Using the venom of the snake Micrurus nigrocinctus as a potent myotoxic agent, this MTT-based technique was evaluated in comparison with available methods based on the measurement of creatine kinase (CK) activity, and a quantitative histological technique considered as a reference. Homogenates of the gastrocnemius muscle prepared in the presence of 1% Triton X-100 reduced MTT and this activity correlated closely with the number of viable cells in the tissue, as determined by histological evaluation. After venom injection, residual MTT-reducing activity of muscle homogenates showed higher correlation to the myonecrosis index obtained by histological analysis, than residual muscle CK activity. Using the new MTT based assay, the ability of an anti-M. nigrocinctus equine antivenom to neutralize venom myotoxins was studied. The myotoxic activity of the venom was completely neutralized using 4 ml antivenom/mg venom, with a 50% effective dose (ED50) value of about 2.5 ml/mg. The MTT-based method described should be useful in the estimation and standardization of anti-myotoxic potency of antivenoms, and in the screening of other neutralizing agents, as a convenient and reliable alternative to the time-consuming quantitative histological methods. PMID- 8505553 TI - Characterization of anti-HLA class II monoclonal antibody LGII-612.14 reacting with formalin fixed tissues. AB - mAb LGII-612.14 derived from a BALB/c mouse immunized with interferon-gamma (IFN gamma) treated cultured human B lymphoid cells LG-2 has been shown with serological and immunochemical assays to recognize a monomorphic determinant expressed on the beta chain of HLA-DR, -DQ and -DP antigens. The linear nature of the determinant, which is likely to be formed by residues 19-25, is indicated by the reactivity of mAb LGII-612.14 with HLA-DR, -DQ and -DP beta chains purified by electrophoresis in presence of SDS. An unusual characteristic of mAb LGII 612.14 is its reactivity with fixed tissue sections. The intensity of staining is affected by the incubation temperature, the incubation time and the fixative used. Maximal intensity of staining of formalin fixed, paraffin embedded tissue sections required an incubation time of 16 h. The intensity of staining of paraffin embedded tissues initially fixed with Bouin's solution, formalin or ethanol was similar to that of frozen tissue sections and stronger than that of tissues fixed with B5 solution. No staining was detected of paraffin embedded tissues fixed with glutaraldehyde or Zenker's solution. Comparison of the staining patterns with mAb LGII-612.14 of frozen and fixed tissue sections showed that the latter substrates provide a superior detail of tissue architecture and cellular morphology without significant loss of sensitivity. Furthermore, comparison of the characteristics of mAb LGII-612.14 with the few previously published anti-HLA class II mAb reacting with fixed tissues indicates that mAb LGII-612.14 stains formalin fixed, paraffin embedded tissues, while mAb 910D7 and TAL-1B5 stain tissues fixed with less commonly used fixatives. Furthermore, mAb LGII-612.14 is likely to yield more sensitive staining results than anti-HLA-DR, DQ and -DP mAb KUL/05. The present results indicate that mAb LGII-612.14 represents a useful probe to apply immunohistochemical techniques to the analysis of the distribution of HLA class II antigens in fixed tissues. This will greatly facilitate the use of readily available collections of fixed tissue specimens in retrospective studies to assess the clinical significance of changes in HLA class II antigen expression which occur in various disease states. PMID- 8505554 TI - An ELISA assay for murine interleukin-1 beta. AB - An ELISA assay was developed for murine IL-1 beta (mIL-1 beta) using a polyclonal antibody generated in rabbits. The antibody was purified by affinity chromatography on protein A coupled to Sepharose followed by chromatography on mIL-1 beta coupled to Sepharose. The protein A and affinity purified populations were compared using radiolabeled mIL-1 beta and the results used to develop the conditions for the ELISA. The assay developed is sensitive to pg/ml concentrations of mIL-1 beta, is comparable in sensitivity to one which uses a hamster monoclonal antibody as the capture antibody, and can be used to detect IL 1 beta in peritoneal washings or tissue lysates from either mouse or rat. There is no cross reaction with any cytokine tested. The use of ELISA enhancement kits can increase the resolution at the lower concentration ranges without affecting assay sensitivity. This assay should prove useful for defining the presence and potential role for IL-1 beta in animal models of disease. PMID- 8505555 TI - Monoclonal antibodies against human hemopexin and their application. AB - Six monoclonal antibodies raised against human serum hemopexin have been characterized. The antibodies reacted with serum hemopexin as well as with the isolated protein in apo-form and with heme-protein complexes on immunoblots obtained following both PAGE and SDS-PAGE. In the case of PAGE blots 1 ng of hemopexin could be detected using a streptavidin-AP detection system. ELISA procedures employing two different pairs of monoclonal antibodies gave working ranges of 0.3-3 mg/l and 10-100 micrograms/l respectively. PMID- 8505556 TI - Dissociation of fluorescein-labelled haptens from polyclonal antibodies. The influence of hapten molecular weight. PMID- 8505557 TI - Prospects for the elimination of Legionnaires' disease. PMID- 8505558 TI - Cerebrospinal fluid lactate in meningitis and meningococcaemia. AB - Cerebrospinal fluid (CSF) lactate values were measured in 26 children with meningitis (12 bacterial, 9 aseptic, 5 partially treated) and five children with meningococcaemia without meningitis. A reference range (0.5-3.2 mmol/l) was established from 100 control children. Amounts of lactate were significantly raised in bacterial meningitis (mean 6.5, range 4.5-10.2) compared with aseptic meningitis (mean 2.6, range 1.1-4.0) but this finding gave little practical help as the bacterial origin of the meningitis was clear from other CSF findings. High values (5.7) in a case of tuberculous meningitis (TBM) suggest that the test may be helpful when other CSF findings are inconclusive. Unless the CSF lactate is raised, the test is of minimal value in partially treated meningitis (mean 3.4, range 1.4-6.2). The previously unobserved finding of increased CSF lactate in meningococcaemia without meningitis (mean 3.9, range 3.1-5.0) supports the view that raised CSF lactate values in bacterial meningitis are not solely due to the presence of neutrophils. Literature relating to CSF lactate is reviewed. PMID- 8505559 TI - The treatment of neonatal meningitis due to gram-negative bacilli with ciprofloxacin: evidence of satisfactory penetration into the cerebrospinal fluid. AB - We describe two cases of neonatal meningitis due to Gram-negative bacilli treated successfully with ciprofloxacin. Examination of serial samples of cerebrospinal fluid indicated the effect of meningeal inflammation on penetration of this drug into the CSF. PMID- 8505560 TI - Diagnosis of Pneumocystis carinii pneumonia in a population of HIV-positive drug users, with particular reference to sputum induction and fluorescent antibody techniques. AB - Between June 1990 and May 1991, 200 sputum inductions were examined by a fluorescent antibody test (FAT) for Pneumocystis carinii (PC). A total of 164 specimens were negative, 36 were positive and a further 20 inductions were unsuccessful. All patients with a positive result, seven of whom had normal chest X-rays and blood gas analyses, were treated for Pneumocystis carinii pneumonia (PCP) with symptomatic response. Two additional patients were diagnosed as PCP during the study period. No patient with a negative or unsuccessful result developed clinical PCP during that admission, although six did develop 10 episodes of PCP (FAT positive for PC on induced sputum samples) within 3 months of a negative result. Sputum induction was well tolerated by patients and not associated with adverse events. Sensitivity of FAT for PC was 95% and specificity was 100%. These results may in part be because most of the patients were injection drug users (IDUs) who often suffer from chronic productive cough, and also because sputum induction in all cases was supervised by an experienced physiotherapist. PMID- 8505561 TI - Interactions of drugs acting against Staphylococcus aureus in vitro and in a mouse model. AB - Two combinations of antibiotics, clindamycin with rifampicin and cloxacillin with netilmicin, were investigated for their activity against two strains of Staphylococcus aureus (a sensitive reference strain and a methicillin-resistant clinical isolate) by means of the in vitro checkerboard technique and an in vivo infected mouse model. The mouse model allowed drug interactions to be evaluated both from the changes in the number of bacteria surviving treatment and from the measured exposure to antibiotics at the site of infection. Specimens from the latter were evaluated twice (day 0 and day 2) in each experiment. The combination of cloxacillin and netilmicin exhibited a synergistic effect against the reference strain both in vitro and in vivo, whereas synergism was obtained under in vitro conditions only against the methicillin-resistant strain. The clindamycin and rifampicin combination acted synergistically or indifferently against both strains in vitro and at day 0 of the in vivo experiments. In contrast, on day 2 of infection, this combination had significantly greater bactericidal effect (synergism) compared to the combination of cloxacillin and netilmicin. These results illustrate the difficulties of interpreting in vitro results for clinical use. PMID- 8505563 TI - Experience of a specialist service for advice on childhood immunisation. AB - We report a 3 year experience of a specialist clinic set up to advise on childhood immunisation. In all, 20 children were referred for advice on their suitability for measles, mumps, rubella (MMR) immunisation and 93 for advice about pertussis immunisation. All of the former and 78 (84%) of the latter were advised that there were no contraindications to their immunisation. The 20 children given MMR vaccine and 55 (71%) of the 78 who were immunised against pertussis had no adverse effects. The clinic serves a small but important group of children who, because of parental or health care professional uncertainty, may not receive protection against potentially damaging or fatal infections. PMID- 8505562 TI - Platelet-activating factor and lipid metabolism in acute malaria. AB - Platelet-activating factor (PAF) contributes to a range of pathophysiological responses in severe illness. To examine PAF metabolism in acute malaria, venous blood was drawn from 10 untreated adults with falciparum malaria, from 8 with untreated vivax malaria, and from 10 controls. Plasma lyso-PAF, produced from PAF through the enzyme acetylhydrolase (AH), was bioassayed, after acetylation to PAF, by platelet [14C]-serotonin release. AH activity was measured by hydrolysis of [3H]-acetyl-PAF. Amounts of plasma lyso-PAF were lower in falciparum (median [range] 24 [9-221] ng/ml) and vivax (35 [7-236] ng/ml) infected patients than in controls (399 [212-504] ng/ml; P < 0.01), and correlated significantly with serum total and HDL-cholesterol (P < 0.001). Plasma AH activities were similar in the control, falciparum and vivax malaria groups. These data suggest that in malaria plasma lyso-PAF values fall together with other blood lipids, but independently of changes in AH activity. This may reflect a generalised decrease in lipid and phospholipid synthesis. However, the reduction of plasma lyso-PAF concentrations in our patients was much greater than that of serum lipoproteins. This is consistent with conversion of lyso-PAF to PAF or with increased PAF-receptor interactions. These two possibilities would have pathophysiological implications. PMID- 8505564 TI - Neonatal cross-infection with Listeria monocytogenes. AB - Transmission of Listeria monocytogenes by food continues to cause concern. Even so, this is not the only means of transmission and neonatal hospital-acquired infection has been well recorded. We report here two cases of perinatal listeriosis one of which was likely to have been due to cross-contamination in a Special Care Baby Unit (SCBU) with equipment acting as the vehicle. PMID- 8505565 TI - Exogenous Nocardia asteroides endophthalmitis following cataract surgery. AB - We present a case of Nocardia asteroides endophthalmitis following cataract surgery. It is the second to be reported and the first in which vision has been preserved. Symptoms commenced 5 days after surgery and there followed a chronic relapsing anterior uveitis which lasted for 4 months. Nocardia asteroides was finally cultured from an aqueous aspirate and a combination of specific antimicrobial treatment and surgery resulted in a satisfactory visual outcome. Exogenous nocardial intraocular infection is rare and must be distinguished from fungal infection as the organism is resistant to antifungal agents. PMID- 8505566 TI - Clostridial endocarditis: report of a case caused by Clostridium septicum and review of the literature. AB - We describe a case of fatal infective endocarditis due to Clostridium septicum in a patient with underlying colonic carcinoma. This is believed to be the first reported case of C. septicum endocarditis. The literature on the subject is reviewed. PMID- 8505567 TI - Mycoplasma hominis sternal wound infection and bacteraemia. AB - Mycoplasma hominis is a rare cause of bacteraemia in adult males. We believe this report to be the first of Mycoplasma hominis bacteraemia and wound infection complicating cardiac surgery. Because of difficulties in isolating the organism, cases may be missed. Review of the literature on M. hominis bacteraemia in adult males reveals that infection is often mild and most often associated with urethral catheterisation. M. hominis is resistant to many antibiotics including erythromycin. If treatment is indicated, tetracycline or clindamycin is the drug of choice. PMID- 8505568 TI - An outbreak of echovirus type 4 infections and its implications for diagnosis and management in general practice. AB - Altogether, 133 patients with Echovirus type 4 infection were studied. Presenting illnesses and reasons for referral to hospital were analyzed. The reason for admission was commonly concern about meningitis, but also an unexplained rash or sore throat. More research is needed in general practice in order to clearly elucidate the spectrum of disease caused by Echoviruses. PMID- 8505569 TI - Epidemiology of Pseudomonas aeruginosa infection in cystic fibrosis and the use of strain genotyping. AB - We describe a study of the epidemiology of Pseudomonas aeruginosa (PA) infection in a group of adults with cystic fibrosis who attended a week-long summer camp in the U.K. Sputum samples were collected from 17 patients at the beginning and at the end of the holiday period. Examination of previous sputum samples had identified 11 patients who were chronically colonised with PA. They shared accommodation during the holiday. The sputum samples from these 11 patients were analysed so as to identify the strains of PA by their genotypic characters. All patients were colonised by unique strains before the beginning of the holiday, with the exception of two pairs of patients whose isolates were indistinguishable. After the holiday, eight of the 11 patients harboured strains of the same genotype as was found in their pre-holiday specimens. In three patients, a strain present post-holiday was different from that found in the pre holiday specimen. In addition, in the case of one patient, two different genotypes were found in the pre-holiday specimen, only one of which was present after the holiday. Evidence of cross-infection of PA during the holiday was not found. Even so, evidence of person-to-person transmission of PA both within the hospital environment and through social contact is presented and discussed. PMID- 8505570 TI - Problems associated with antiprotozoan and anthelmintic chemoprophylaxis/chemotherapy during pregnancy. PMID- 8505571 TI - Localisation of the ampicillin-resistance gene in isolates of Haemophilus influenzae in Hong Kong. PMID- 8505572 TI - Corynebacterium striatum: a clinically significant isolate from sputum in chronic obstructive airways disease. PMID- 8505573 TI - Disseminated Exserohilum infection. PMID- 8505574 TI - Post-myelography meningoencephalitis caused by Streptococcus agalactiae. PMID- 8505575 TI - Suppurative thyroiditis due to Nocardia asteroides. PMID- 8505576 TI - Haemophilus influenzae as a rare cause of CAPD peritonitis. PMID- 8505577 TI - Tenchkoff catheter-associated peritonitis caused by Corynebacterium group I2. PMID- 8505578 TI - Detection of faecal IgA in the diagnosis of infection by Escherichia coli O157. PMID- 8505579 TI - Tuberculosis/HIV co-infection in India's north-eastern states. PMID- 8505580 TI - Isolation of Brucella melitensis from human milk. PMID- 8505581 TI - Under-reporting of malaria, a notifiable disease, in Britain. PMID- 8505582 TI - Early confirmation of HIV p24 antigenaemia in infants born of HIV-positive mothers. PMID- 8505583 TI - Enhanced activity of lysosomal beta-galactosidase after silicone implantation: an experimental study in rats. PMID- 8505584 TI - The rising tide of tuberculosis and the human host response to Mycobacterium tuberculosis. PMID- 8505585 TI - Enhanced activity of lysosomal beta-galactosidase after silicone implantation: an experimental study in rats. AB - Biologic consequences of silicone implantation may include changes in host connective tissue metabolism. Lysosomal beta-galactosidase (beta-GAL) activity, which is a sensitive marker of fibrotic diseases and may be a useful marker of collagen turnover, was examined in the serum of rats with implanted silicones. No significant difference in spectrofluorometrically determined enzyme activity was demonstrated in rats subjected to dorsal submuscular pocket dissection without implantation and corresponding nonoperative controls. Rats with implanted solid silicone elastomer or free polydimethylsiloxane gel (both components obtained from mammary implant) revealed enhanced activity of serum beta-GAL. Higher enzyme activity was observed in animals with implanted silicone gel with a peak level of 2.73 +/- 0.08 pmol/30 min/ml 16 weeks after implantation. Increased collagen deposition and capsular thickness was demonstrated around implanted gel material as compared with that around elastomer shell. Animals with implanted absorbable and nonabsorbable materials, polyglactin and Teflon (polytetrafluoroethylene), respectively, after initial increase of beta-GAL activity demonstrated enzyme activity within the normal range. Findings indicate that there is enhanced lysosomal beta-GAL activity after silicone implantation in rats. Clinical relevance and its possible significance as a predictor or indicator of local or systemic fibrosis after silicone implantation seems worthy of further investigation. PMID- 8505587 TI - Fatty acid ethyl esters increase rat pancreatic lysosomal fragility. AB - Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol has been shown to increase rat pancreatic lysosomal fragility. Fatty acid ethyl esters (nonoxidative products of ethanol metabolism) accumulate in the pancreas after ethanol consumption. The aim of this study was to determine whether the lysosomal fragility observed after ethanol could be mediated by fatty acid ethyl esters. Rat pancreatic lysosomes were incubated for 20 minutes at 20 degrees C with ethyl oleate (a representative fatty acid ethyl ester). Lysosomal stability was then assessed by determination of (1) latency (i.e., the percent increase in lysosomal enzyme activity after addition of Triton X-100) and (2) supernatant activity (i.e., the proportion of lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes). N-acetyl glucosaminidase and cathepsin B were assayed as lysosomal marker enzymes. Lysosomes incubated with buffer alone were used as controls. Ethyl oleate at concentrations above 140 mumol/L increased pancreatic lysosomal fragility as demonstrated by decreased latency. Increased percentage of enzyme in the supernatant was observed at higher concentrations. These results suggest that increased pancreatic lysosomal fragility observed with ethanol may be mediated by fatty acid ethyl esters. PMID- 8505586 TI - The role of glutathione in bile secretion of endogenous trace elements in rats. AB - To evaluate the role of glutathione in biliary secretion of endogenous trace elements, we quantitated trace element output rates by proton-induced x-ray emission under various conditions with altered biliary glutathione secretion and hepatic glutathione content in the rat. Treatment with phenobarbital (80 mg/kg body weight, 4 days), ethanol (0.9 gm/kg body weight, 4 days), or diethylmaleate (3.9 mmol/kg body weight) resulted in changes in biliary glutathione secretion of +114%, -56%, and -95%, respectively, and in hepatic glutathione content of -0%, +25%, and -86%, respectively, when compared with control values. Biliary glutathione level was below detection limits in mutant Groningen Yellow Wistar rats, whereas hepatic glutathione content was increased by 114% in these animals. Glutathione secretion showed a linear relationship with bile flow when data from all experiments were included in the analysis; the apparent choleretic activity of glutathione was 67 microliters/mumol. Six trace elements (iron, zinc, copper, manganese, molybdenum, bromine) could always be detected in bile. Potassium and calcium were measured for comparative purposes. No relation was found between biliary trace element secretion and hepatic glutathione content. Biliary output rates of iron, molybdenum, and bromine correlated, albeit poorly, with biliary glutathione efflux (r values: iron, 0.67; molybdenum, 0.40; bromine, 0.53; respectively). Copper, manganese, and zinc secretion did not show any consistent relationship with glutathione secretion. The secretion rates of iron, molybdenum, and bromine, like that of calcium, showed a highly significant correlation with bile flow (r values: iron, 0.89; molybdenum, 0.75; bromine, 0.80; and calcium, 0.90; respectively, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505588 TI - Decreased serum cholesterol level after snake bite (Vipera palaestinae) as a marker of severity of envenomation. AB - In 44 patients bitten by snakes (Vipera palaestinae), admission serum cholesterol levels were negatively correlated with severity of envenomation (mean +/- SD, 175 +/- 49, 137 +/- 36, and 96 +/- 40 mg/dl, respectively, in cases with mild, moderate, and severe clinical manifestations [p < 0.0001]). Concomitant decreases in serum albumin were not significant. These findings were supported by experimental results in rabbits, in which low, medium, and high doses of purified V. palaestinae venom (all in the non-lethal range), led to dose-dependent decreases in serum cholesterol, at 180 minutes, of 9.5% +/- 8.9%, 18.6% +/- 10.1%, and 32.7% +/- 11.8%, respectively (p < 0.01). This rapid decrease in serum cholesterol level is only partially explained by transcapillary lipoprotein leakage and probably indicates changes in lipoprotein transport and metabolism caused by the phospholipase A2 component of V. palaestinae venom. Admission total serum cholesterol level may serve as an indicator of severity of envenomation in patients bitten by snakes of the Vipera genus before full development of the clinical syndrome. PMID- 8505589 TI - Arteriovenous differences and tissue concentrations of branched-chain ketoacids. AB - According to previous reports, branched chain ketoacids (BCKAs) are undetectable in liver and brain. A procedure is described for HPLC analysis of tissue concentrations of BCKA that achieves 80% recovery of labeled 2-ketoisocaproate (KIC) added to frozen powdered liver. In normal overnight-fasted rats, substantial hepatic uptake was demonstrable in the order KIC > 2-ketoisovalerate (KIV) congruent to 2-keto-3-methylvalerate (KMV). All three BCKAs were very low in freeze-clamped liver. Liver concentrations were only 15% to 22% of the mean of portal vein, hepatic vein, and hepatic artery (aorta) concentrations. In view of the probable contribution to total liver content of extracellular BCKAs, the intracellular concentrations in liver tissue must be vanishingly low. Somewhat higher amounts were present in freeze-clamped kidney and heart tissue, and significant uptake of KIC and KMV by kidney was found. Brain released KIC. Muscle contained concentrations of BCKA that were 35% to 72% of concentrations in plasma, and it released all three BCKAs. Similar results were obtained from tissues in overnight-fasted dogs, except that even lower levels were found in freeze-clamped brain (sampled before circulation ceased) than were found in the liver. Plasma levels in dogs were similar to those of rats. In both species the tissue-to-plasma ratios were higher for KIV than for KMV or KIC. Remarkably low BCKA levels in liver and brain are unexplained, particularly in light of evidence that BCKAs gain access to cells in both organs. PMID- 8505590 TI - Immunologic specificity of IgG against trimellityl-human serum albumin in serum samples of workers exposed to trimellitic anhydride. AB - The specificity of immunoglobulin G (IgG) against trimellityl-human serum albumin (TM-HSA) in serum samples from 11 workers exposed to trimellitic anhydride (TMA) was characterized in this study. Levels of IgG against TM-HSA and HSA-conjugates of other acid anhydrides, phthalic anhydride (PA), maleic anhydride (MA), hexahydrophthalic anhydride (HHPA) and tetrachlorophthalic anhydride (TCPA) were estimated by enzyme-linked immunosorbent assay index. Inhibition studies using each of 5 HSA acid anhydride conjugates were performed on all 11 serum samples with IgG against TM-HSA, and on the three serum samples with highest IgG binding to P-HSA and M-HSA. The only conjugate capable of inhibiting TM-HSA was TM-HSA. Both P-HSA and TM-HSA were able to inhibit IgG bound to P-HSA, and all other anhydride conjugates were able to inhibit IgG bound to M-HSA to some degree. When using TM-HSA and the other anhydride-HSA conjugates to inhibit IgG against TM HSA, cross-reactivity was not apparent. However, when using those same conjugates to inhibit IgG against P-HSA or M-HSA, cross-reactivity could be demonstrated in some serum samples. Thus TMA workers may have antibody that has some affinity for other anhydride-HSA conjugates, but this antibody cannot be demonstrated by inhibition studies of IgG against TM-HSA when using other acid anhydride-HSA conjugates. Further studies are needed to define the biologic relevance of these immunologic observations. PMID- 8505591 TI - Are megakaryocytes and endothelial cells sisters? AB - Megakaryocytes and endothelial cells, two important blood and vascular cells, share many similar antigens on their surfaces and in the cytoplasm. It is known that the two types of cells share several developmental regulators: fibroblast growth factors, granulocyte-macrophage colony-stimulating factor, heparin and heparan sulfate, platelet factor 4, transforming growth factor-beta, gamma interferon, and thrombospondin. Recognition of these common factors and studies with them are broadening the understanding of the pathogenesis of megakaryocytic and angiogenic diseases and encouraging attempts to develop new therapeutic strategies for the future. PMID- 8505592 TI - Reaction time drifts identify objects of attention in pigeon visual search. AB - Three pigeons searched for a unique target form among 31 identical distractors, and search reaction time (RT) was measured. Within experiments, target and distractor on each trial were drawn from the same small set of forms that differed from each other by simple features. Correlations across sessions among RTs to the various form pairs were analyzed. Experiment 1 indicated drifts of attention between the top of the forms, where a gap might appear, and the bottom, where a line might appear, and also suggested drifts of attention to the line as a target feature. Experiment 2 indicated similar drifts between the top and bottom of the forms and between small differences and large differences in target features. Attention to intraform location appeared relatively independent of attention to target features. The method provides a new way to identify functionally separable aspects of stimulus processing and to describe their temporal properties. PMID- 8505593 TI - Mechanisms responsible for reduced contextual conditioning with massed unsignaled unconditional stimuli. AB - Massed presentation of unsignaled shock results in less conditional freezing to contextual cues than do distributed presentations. Consistent with an account of the learning deficit based on the perceptual-defensive-recuperative theory, the massed-shock deficit was attenuated by preexposure to shock or the conditioning context. This formulation was also successfully applied to the deficit in conditioning that occurs when a single shock is given immediately after placement in a context. Opponent-process theory was not supported by 2 findings: (a) The deficit was neither enhanced by shock preexposure nor reduced by an opioid antagonist, and (b) unconditional reactions were greater with massed shock. Inconsistent with the suggestion that the effect is a performance artifact specific to freezing, the massed-shock deficit was apparent for a 2nd measure of conditioning. PMID- 8505594 TI - Effects of response strategy and retention interval on performance of Clark's nutcrackers in a radial maze analogue. AB - Two groups of Clark's nutcrackers (Nucifraga columbiana) were trained to use either a stay or shift response strategy in a radial maze analogue. Each trial had a preretention stage, a retention interval, and a postretention test. In Experiment 1, acquisition with a 5-min retention interval was studied. Response strategy did not affect the rate at which the task was learned. Performance following longer retention intervals was tested in Experiments 2-4. Changes in retention intervals were presented in trial blocks of increasing duration in Experiment 2 and were randomly presented between trials in Experiment 3. Experiment 4 extended the retention interval to 24 hr. No difference in performance was found between the 2 groups in any of these experiments. These results suggest a flexible relationship between spatial memory and response requirement in food-hoarding birds for at least 1 spatial memory task. PMID- 8505595 TI - Numerosity discrimination: both time and number matter. AB - Pigeons were trained on a psychophysical choice task to discriminate between 2 fixed ratios and tested with probe ratios intermediate to the training requirements. Absolute and relative ratio size were varied over conditions. In a final condition, subjects were transferred from the number-based discrimination to a time-based discrimination. The times taken to emit the ratios were recorded, and ratio value and ratio time were used to predict choice in a multiple regression analysis. Psychophysical analyses of the response number dimension suggested a scalar counting principle of numerosity discrimination, similar to that found with temporal dimensions. The multiple regression analysis indicated that both number and time contributed to the discrimination of ratio value. The results of the transfer test indicated individual differences in the degree to which responding was controlled by temporal versus numerical factors. PMID- 8505596 TI - Birth control. PMID- 8505597 TI - Vitamin B12 deficiency. PMID- 8505598 TI - Chaperones. PMID- 8505599 TI - Americans with Disabilities Act. PMID- 8505600 TI - Tobacco control: toward the year 2000. PMID- 8505601 TI - Primary care physician consultations. PMID- 8505602 TI - Concurrent care: an ethical issue for family physicians. PMID- 8505603 TI - Prevalence and severity of urinary incontinence in ambulatory adults: an UPRNet study. AB - BACKGROUND: Although urinary incontinence (UI) is a common and costly problem, its prevalence and severity in ambulatory patients is not well established. The main objectives of this study were to define the prevalence and severity of urinary incontinence in adult men and women who came to a primary care office for health care, to determine if these patients had ever told a health care provider about this problem, and to determine if they would be interested in treatment if it were available and effective. METHODS: Men and women aged 20 years and over who came to family physicians' offices seeking health care for any reason during an 11-week period were the subjects of a survey by an anonymous questionnaire. Five family practice offices in UPRNet (the Upper Peninsula Research Network), a research network in Michigan, participated. We defined "current urinary incontinence" as any degree of incontinence in the past 12 months. RESULTS: Of the 2830 study participants, 33% had current urinary incontinence (95% confidence interval [CI] 31% to 35%). Incontinence was experienced by 11% of the men and 43% of the women. Urinary incontinence constituting a social or hygienic problem was reported by 5% of the men and 23% of the women (17% overall). Of those with current UI, 72% had not told a health care provider. Of the patients who had not told a physician, 37% said they would seek care if they knew tests and effective treatment were available. CONCLUSIONS: Urinary incontinence is a common problem among those seen in primary care settings, and its presence is often not known to the health care provider. PMID- 8505604 TI - Association between epidural analgesia during labor and fever. AB - BACKGROUND: Epidural analgesia has been associated in previous research with an increase in maternal temperature. METHODS: Three studies were done: a retrospective chart review of women in labor, a prospective cohort study of women in labor, and a case-control study of newborns with fever. The prospective study enrolled 28 women, 14 of whom received epidural analgesia. Maternal temperature was measured hourly with a tympanic membrane thermometer. Other variables examined included duration of labor, duration of ruptured membranes, and room temperature. To further explore the possible association between maternal epidural exposure and newborn fever, a case-control study of newborns with fever at birth was carried out. RESULTS: In both the retrospective and prospective studies of women in labor, the duration of epidural analgesia was correlated with maximum maternal temperature during labor, with an increase, in the prospective study, of 0.07 degrees C per hour of exposure to epidural analgesia (P = .002). Controlling for other variables did not change the magnitude of this effect or its statistical significance. Similar trends were seen in the newborn's first temperature in both the prospective study of women in labor and the case-control study of newborns, but the associations were not significant (P = .07 and .08, respectively). CONCLUSIONS: Epidural analgesia is associated with an increase in maternal temperature during labor and possibly with an elevation of newborns' first temperatures. PMID- 8505605 TI - Full-thickness leg ulcers: patient demographics and predictors of healing. Multi Center Leg Ulcer Study Group. AB - BACKGROUND: Despite increased knowledge about the immediate and underlying causes of chronic leg ulcers, their management remains a challenge. Some ulcers rapidly respond to treatment whereas others do not, and the decision to reassess the patient and treatment modality is usually based on the clinician's own experience. METHODS: Following diagnosis of the underlying cause of leg ulcers, 181 patients were screened. The use of a hydrocolloid dressing (DuoDERM) was evaluated in the treatment of 61 patients with 72 full-thickness ulcers. Patient characteristics associated with deep wounds as well as patient and wound characteristics predictive of the extent of healing and time required for healing were identified. RESULTS: Patients with full-thickness ulcers were more likely to be overweight (P < .001) and not fully mobile (P = .016). During a mean treatment time of 56 days, 54% of the full-thickness ulcers healed. Ulcers were less likely to heal if the patients were men (P = .02) or had diabetes mellitus (P < .003). A > 30% reduction in ulcer area after 2 weeks of treatment was a predictor of both treatment outcome (P = .016) and time required for healing (P = .004). Odor at baseline and advanced age also were associated with increased time required for healing (P = .005 and .017, respectively). CONCLUSIONS: Noninvasive clinical assessments can aid the clinician in predicting treatment outcome and may facilitate the decision to change therapy and evaluate treatment compliance. PMID- 8505606 TI - Self-reported medical problems of adult female survivors of childhood sexual abuse. AB - BACKGROUND: Childhood sexual abuse has been established as an antecedent to specific psychological disorders in adulthood. Only recently have researchers begun to consider the effects of this early trauma on subsequent physical health status. The current study sought to explore the relationship between a history of childhood sexual abuse in female adults and subsequent self-reported medical complaints. METHODS: This consecutive sample study used a questionnaire to distinguish subjects with a sexual abuse history and those without such a history. Subjects were female patients over 18 years of age at a primary care health center. RESULTS: Twenty-six percent of the 523 subjects who completed the entire questionnaire acknowledged a history of sexual abuse in childhood. This percentage is consistent with estimates for the population at large. The abused group reported more problems in respiratory, gastrointestinal, musculoskeletal, neurological, and gynecological functions. Statistically significant discriminating variables for those who had been abused were (1) total medical complaints reported, (2) previous mental health treatment, and (3) age of first sexual intercourse. Among the abused group, only 5.1% had ever disclosed information about their sexual abuse experiences to a physician. CONCLUSIONS: At least one in four women are survivors of childhood sexual abuse. These women rarely spontaneously reveal this history to a physician, yet they are more likely than nonabused patients to report multisystemic medical complaints. To avoid misdiagnosis and misuse of medical services, physicians should routinely obtain a thorough sexual history, particularly when the patient has multisystem complaints. PMID- 8505607 TI - Effect of type II diabetes mellitus on cognitive function. AB - BACKGROUND: As people with diabetes mellitus suffer from peripheral and autonomic neuropathy, we thought it possible that deficits in cognitive function might also be found. Our objective was to compare the cognitive function of elderly persons with non-insulin-dependent diabetes mellitus (NIDDM) with a matched sample of persons without NIDDM: METHODS: Ninety outpatients over 50 years of age with NIDDM and 90 matched nondiabetic patients were recruited for the study. The Modified Mini-Mental State (3MS) and the Delayed Word Recall (DWR) test were used to assess cognitive function. RESULTS: On the 3MS test, the mean score of persons with NIDDM was 75.6, and that of nondiabetic persons was 79.5 (two-tailed t = 3.04, P = .013). On the DWR, the mean score of persons with NIDDM was 3.9, and that of persons without NIDDM was 4.7 (two-tailed t = 3.52, P = .012). CONCLUSIONS: Persons with NIDDM had significantly poorer scores on two tests of cognitive function. Physicians should be aware of this association between type II diabetes and a small but definite impairment of cognitive function. PMID- 8505608 TI - Physician-patient sexual contact: ethical and legal issues and clinical guidelines. AB - Although sexual relationships between mental health professionals and patients have been the subject of research, ethical writing, and legislation during recent years, there has been comparatively little attention given to this problem in primary care medicine. An estimated 11% of family physicians have had sexual contact with at least one of their patients. Recently, the American Medical Association presented ethical guidelines addressing this issue. Acceptable conditions under which a physician may become involved with a former patient are not well addressed by these guidelines. Although sexual involvement with patients appears to exist on an ethical continuum, it inevitably results in diminished patient autonomy. Sexual contact between patients and mental health professionals is now explicitly illegal in many states, but comparable legislation has not been enacted for nonpsychiatric physicians. There is evidence that when sexual contact between a physician and a patient occurs, the patient suffers long-term psychological consequences. PMID- 8505609 TI - In search of the 'back mouse'. AB - The "back mouse" is a tender, fibrous, fatty subcutaneous nodule found in the lumbosacral area in up to 16% of people. It can be a treatable cause of low back pain that may be unrecognized by both specialists and generalists. PMID- 8505610 TI - Two central nervous system infectious diseases in a patient with AIDS. AB - As medical interventions prolong the lives of patients with acquired immunodeficiency syndrome (AIDS), we have begun to observe multiple infections occurring simultaneously in a single patient. This report describes two central nervous system (CNS) infections, cryptococcal meningitis and cerebral toxoplasmosis, coexisting in a patient with AIDS. Although the treatment strategies for these CNS infections are generally established, often the physician must make management decisions based on clinical and statistical data and patient response to empiric trials of therapy rather than on the results of invasive diagnostic tests. PMID- 8505612 TI - Preserving quality care. PMID- 8505611 TI - Malaise in the primary care pasture. PMID- 8505613 TI - Office of Inspector General U.S. Department of Health and Human Services. An overview. AB - It has become increasingly important for physicians to be aware of the various legal liabilities regarding licensure they face in the daily practice of medicine. This includes issues related to fraud, waste and abuse. It has become a common refrain that physicians promote significant abusive and possibly fraudulent practices. This article describes the organization, function and work plans of the Office of Inspector General, Department of Health and Human Services. A structural guideline is presented based upon conviction and recovery rates to allow physicians to understand the scope of the problem in greater depth. PMID- 8505614 TI - Hemochromatosis and celiac sprue. Case report. AB - The patient presented with apparent hemochromatosis and celiac sprue, a unique combination not previously reported. Almost all patients with celiac sprue have an iron deficiency which is usually present very early, often antedating other manifestations of the condition. PMID- 8505615 TI - AIDS epidemic among Florida women. AB - Impact of the human immunodeficiency virus among women in Florida is increasingly recognized in the second decade of the AIDS epidemic. Illicit drug use, sexual activity with multiple partners, lack of access to health care, and socioeconomic disadvantages are greatly contributing to the increase of female AIDS cases. Current salient features of the epidemic are summarized as well as prevention strategies to reduce transmission of the virus. PMID- 8505616 TI - Emergency room care for hemophiliac patients. Understanding and overcoming difficulties. AB - Hemophiliac patients represent a unique challenge to emergency room physicians. They are particularly well educated and experienced in their disease and its treatment, whereas emergency room doctors may have little experience with management. This paradoxical situation often leads to frustration for both; it need not be this way. Using a new paradigm of a patient-physician relationship, the patient's knowledge, experience and intuition can enhance the physician's diagnostic abilities. Together both can transform a potentially adversarial relationship into one which is mutually empowering and healing. PMID- 8505617 TI - Comparison of German and United States malpractice systems. AB - Germany has successfully contained overall health-care costs while providing virtually universal access to high quality services. The country's medical and legal systems create a climate characterized by less pressure for malpractice litigation and greater efficiency of resolution. This analysis reviews characteristics that may be useful in reducing the $20 billion annual costs associated with medical malpractice in the United States. Some features of the German model may be unattractive. Further investigation appears warranted. PMID- 8505618 TI - Medical decisions at the end of life. PMID- 8505619 TI - Intimacy in medicine. Healing the heart of the patient-physician relationship. PMID- 8505620 TI - Why us? PMID- 8505621 TI - Is there a future in your future? PMID- 8505622 TI - Reality riptide. PMID- 8505623 TI - Occupational medicine. PMID- 8505624 TI - Theory support. PMID- 8505625 TI - High ionic strength and low pH detain activated skinned rabbit skeletal muscle crossbridges in a low force state. AB - The effects of varying pH and ionic strength on the force-velocity relations and tension transients of skinned rabbit skeletal muscle were studied at 1-2 degrees C. Both decreasing pH from 7.35 to 6.35 and raising ionic strength from 125 to 360 mM reduced isometric force by about half and decreased sarcomere stiffness by about one-fourth, so that the stiffness/force ratio was increased by half. Lowering pH also decreased maximum shortening velocity by approximately 29%, while increasing ionic strength had little effect on velocity. These effects on velocity were correlated with asymmetrical effects on stiffness. The increase in the stiffness/force ratio with both interventions was manifest as a greater relative force change associated with a sarcomere length step. This force difference persisted for a variable time after the step. At the high ionic strength the force difference was long-lasting after stretches but relaxed quickly after releases, suggesting that the structures responsible would not impose much resistance to steady-state shortening. The opposite was found in the low pH experiments. The force difference relaxed quickly after stretches but persisted for a long time after releases. Furthermore, this force difference reached a constant value of approximately 8% of isometric force with intermediate sizes of release, and was not increased with larger releases. This value was almost identical to the value of an internal load that would be sufficient to account for the reduction in maximum velocity seen at the low pH. The results are interpreted as showing that both low pH and high ionic strength inhibit the movement of crossbridges into the force-generating parts of their cycle after they have attached to the actin filaments, with very few other effects on the cycle. The two interventions are different, however, in that detained bridges can be detached readily by shortening when the detention is caused by high ionic strength but not when it is caused by low pH. PMID- 8505626 TI - A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. AB - The electrophysiological properties of HK2 (Kv1.5), a K+ channel cloned from human ventricle, were investigated after stable expression in a mouse Ltk- cell line. Cell lines that expressed HK2 mRNA displayed a current with delayed rectifier properties at 23 degrees C, while sham transfected cell lines showed neither specific HK2 mRNA hybridization nor voltage-activated currents under whole cell conditions. The expression of the HK2 current has been stable for over two years. The dependence of the reversal potential of this current on the external K+ concentration (55 mV/decade) confirmed K+ selectivity, and the tail envelope test was satisfied, indicating expression of a single population of K+ channels. The activation time course was fast and sigmoidal (time constants declined from 10 ms to < 2 ms between 0 and +60 mV). The midpoint and slope factor of the activation curve were Eh = -14 +/- 5 mV and k = 5.9 +/- 0.9 (n = 31), respectively. Slow partial inactivation was observed especially at large depolarizations (20 +/- 2% after 250 ms at +60 mV, n = 32), and was incomplete in 5 s (69 +/- 3%, n = 14). This slow inactivation appeared to be a genuine gating process and not due to K+ accumulation, because it was present regardless of the size of the current and was observed even with 140 mM external K+ concentration. Slow inactivation had a biexponential time course with largely voltage independent time constants of approximately 240 and 2,700 ms between -10 and +60 mV. The voltage dependence of slow inactivation overlapped with that of activation: Eh = -25 +/- 4 mV and k = 3.7 +/- 0.7 (n = 14). The fully activated current-voltage relationship displayed outward rectification in 4 mM external K+ concentration, but was more linear at higher external K+ concentrations, changes that could be explained in part on the basis of constant field (Goldman-Hodgkin Katz) rectification. Activation and inactivation kinetics displayed a marked temperature dependence, resulting in faster activation and enhanced inactivation at higher temperature. The current was sensitive to low concentrations of 4 aminopyridine, but relatively insensitive to external TEA and to high concentrations of dendrotoxin. The expressed current did not resemble either the rapid or the slow components of delayed rectification described in guinea pig myocytes. However, this channel has many similarities to the rapidly activating delayed rectifying currents described in adult rat atrial and neonatal canine epicardial myocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8505627 TI - The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis. AB - Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half-activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least-squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation. PMID- 8505628 TI - The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II. Closed state reverse use-dependent block by 4 aminopyridine. AB - Block of the calcium-independent transient outward K+ current, I(to), by 4 aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use-dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in which the peak current is delayed in the presence of 4 AP at depolarized potentials; (d) relief of block at depolarized potentials which is concentration dependent and parallels steady-state inactivation for low 4-AP concentrations (V1/2 approximately -10 mV in 0.1 mM 4-AP) and steady-state activation at higher concentrations (V1/2 = +7 mV in 1 mM 4-AP, +15 mV in 10 mM 4 AP); and (e) reassociation of 4-AP at hyperpolarized potentials. No evidence for interaction of 4-AP with either the open or inactivated state of the I(to) channel was obtained from measurements of kinetics of recovery and deactivation in the presence of 0.5-1.0 mM 4-AP. At hyperpolarized potentials (-30 to -90 mV) 10 mM 4-AP associates slowly (time constants ranging from approximately 800 to 1,300 ms) with the closed states of the channel (apparent Kd approximately 0.2 mM). From -90 to -20 mV the affinity of the I(to) channel for 4-AP appears to be voltage insensitive; however, at depolarized potentials (+20 to +100 mV) 4-AP dissociates with time constants ranging from approximately 350 to 150 ms. Consequently, the properties of 4-AP binding to the I(to) channel undergo a transition in the range of potentials over which channel activation and inactivation occurs (-30 to +20 mV). We propose a closed state model of I(to) channel gating and 4-AP binding kinetics, in which 4-AP binds to three closed states. In this model 4-AP has a progressively lower affinity as the channel approaches the open state, but has no intrinsic voltage dependence of binding. PMID- 8505629 TI - Coagulation abnormalities and cerebral infarction. PMID- 8505630 TI - Karl Friedrich Hieronymus von Munchausen (1720-97). PMID- 8505631 TI - Head injury. PMID- 8505632 TI - Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures. AB - The results of a multicentre, randomised, double-blind, placebo controlled, crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs (AEDs) are presented. The study consisted of two 12 week treatment periods each followed by a four week washout period. During the lamotrigine treatment phase, patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1-3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study. There was a highly significant (p < 0.001) decrease in total seizure counts on lamotrigine compared with placebo. Overall, 22% of patients experienced at least a 50% reduction in the total numbers of all seizures types on lamotrigine, compared with none on placebo. When the total numbers of partial seizures (simple and complex partial) were analysed there was also a significant (p < 0.05) reduction in seizure counts on lamotrigine compared with placebo. When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance (0.05 < p < 0.1). Concomitant AED plasma concentrations were virtually unchanged. It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures. PMID- 8505633 TI - Motor neuron disease and multiple sclerosis among immigrants to England from the Indian subcontinent, the Caribbean, and east and west Africa. AB - The mortality from motor neuron disease (MND) and multiple sclerosis (MS) was studied among immigrants to England and Wales from the Indian subcontinent, the Caribbean, and East and West Africa during the 10 years 1979-88. The MND mortality among ethnic Asian males was only half and for females one fifth of that expected at English rates. MND mortality in Caribbean immigrants was somewhat lower than expected. White immigrants from the Indian subcontinent had the expected MND mortality. MS mortality was low among Asian, West Indian, and African immigrants. This study is evidence that MND mortality is not the same in all ethnic groups. PMID- 8505634 TI - The relation of alcohol consumption to cardiovascular risk factors and stroke. The west Birmingham stroke project. AB - The disputed relation between recent alcohol consumption and stroke was examined in a community case control study. One hundred and twenty five incident first time stroke patients and 198 controls, aged 35 to 74 years, were recruited over two years from a general practice population. The age and sex adjusted relative risks for stroke by recent weekly "drinks" of alcohol were; 0-1.0 (reference), 1 to 14-0.57, 15 to 29-0.63, and > 29-0.99. Among the controls it was noted that non-drinkers were more likely than light/moderate drinkers (1 to 29 drinks per week) to have the following characteristics; history of obesity (p < 0.001), not a recent walker (p < 0.05), and no vigorous exercise in early adulthood (p < 0.01). The apparent association of light and moderate alcohol consumption with decreased stroke risk disappeared when these variables were included in the multiple risk factor adjusted analysis; 0-1.0, 1 to 14-0.88, 15 to 29-1.11, and > 29-1.23. The pattern for proved cerebral infarction (n = 81) was similar. The results of this study do not support the idea that recent heavy alcohol consumption is an important cause of either overall stroke or cerebral infarction. The association of non-drinking with a history of overweight and inactivity may explain the apparent protective effect of lighter alcohol consumption on the risks of both stroke and coronary heart disease. PMID- 8505635 TI - Selection of acute stroke patients for treatment of visual neglect. AB - Although visual neglect is a predictor of poor outcome after stroke, some patients regain independence, whilst others take up considerable rehabilitation resources. Intensive treatment of visual neglect is available and a knowledge of the predictive features in the recovery of these patients would be helpful in the early selection of patients for treatment. A study was therefore carried out to determine the prognosis of patients presenting with visual neglect at two to three days after stroke. Linear logistic regression showed that the initial degree of paralysis (measured by the Motricity Index), the severity of neglect (measured by the Visual Neglect Recovery Index) and the patient's age were the significant predictors of independence (Barthel score 20), mild dependence (Barthel 15-19), and moderate/severe dependence (Barthel 0-14) in surviving patients at three months and at six months. Regression equations correctly predicted 78% of outcomes, and had a sensitivity and specificity for "independence" of 84% and 90% respectively, and a sensitivity and specificity for "moderate/severe dependence" of 89% and 80%. It is suggested that these equations may be useful in selecting comparable groups of patients for randomised controlled trials of treatment of visual neglect. PMID- 8505637 TI - Familial progressive supranuclear palsy. AB - A progressive extrapyramidal syndrome and dementia occurred in three members of one family. The age of onset was in the seventh decade and the affected individuals showed many of the clinical features of progressive supranuclear palsy (PSP). Necropsy of one individual revealed the neuropathological features of PSP. We propose that this family has a familial form of PSP and review the evidence in the literature that a familial form exists. PMID- 8505636 TI - Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study. AB - Striatal dopamine D1 receptors were investigated in 11 patients with Parkinson's disease (PD), five patients with striatonigral degeneration (SND) and six age matched controls by positron emission tomography and carbon-11 labelled SCH23390. The SND patients showed mean 12%, 21%, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen, and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients. The results may explain the different therapeutic responses to levadopa between SND and PD patients, and this technique might prove useful for their differentiation. PMID- 8505638 TI - No evidence for altered muscle mitochondrial function in Parkinson's disease. AB - Recent reports indicate that reductions in mitochondrial respiratory chain function occur in substantia nigra, platelets, and muscle from patients with Parkinson's disease. To confirm and further characterise the presence of a generally distributed mitochondrial defect, mitochondrial metabolism was evaluated in muscle obtained from subjects with Parkinson's disease and from normal controls. Oxygen consumption rates in muscle mitochondria represented by complex I, complexes II-III, or complex IV did not differ between the two groups. Likewise, activities of rotenone sensitive NADH cytochrome c reductase, succinate cytochrome c reductase, or cytochrome oxidase in muscle mitochondria were not significantly different between Parkinsonian and control subjects. These findings fail to provide support for a generalised defect in mitochondrial function in Parkinson's disease but do not exclude an abnormality in respiratory function confined to the substantia nigra. PMID- 8505639 TI - Neuronal number and volume alterations in the neocortex of HIV infected individuals. AB - Substantial neuronal loss in the superior frontal gyrus in patients who have died of AIDS have been reported previously. This investigation examined the distribution of neuronal loss in three other neocortical areas and, alteration in neuronal volume in four neocortical areas. This was carried out using two stereological probes, the "disector" and the "nucleator". These recently developed methods provide estimations, regardless of size and shape, in real three-dimensional space, and are more efficient than conventional quantitation. The study was performed on 12 HIV infected individuals and nine controls. The HIV group had no neuropathological evidence of opportunistic infections or neoplasms, five had HIV encephalitis and the remaining seven had only minimal pathology. There was significant neuronal loss of 30% (p = 0.018) in the calcarine cortex (primary visual area), and loss of 18% in the superior parietal lobule which just failed to reach significance. This loss was not related to the presence of HIV encephalitis. The mean neuronal volume was increased in the occipital area by 29% (p = 0.028) and the frequency of large neurons (over 2000 microns 3) doubled in the frontal (p < 0.05) and parietal (p < 0.02) areas. The results confirm the hypothesis that HIV infection is associated with neuronal injury and death, and suggest that increase in neuronal size may be a feature of the cytopathology of this condition. PMID- 8505640 TI - Neuronal loss in the hippocampus in Huntington's disease: a comparison with HIV infection. AB - The hippocampus is usually affected in primary dementias and the pathological changes may be severe. Knowledge of hippocampal pathology in HIV infection and Huntington's disease (HD), however, is extremely limited. A stereological technique (the optical "disector") has been used to assess neuronal populations in four areas of the hippocampus in 11 patients with HIV infection and in nine patients with HD. The HIV patients died without opportunistic infections or neoplasms affecting the brain; they had HIV encephalitis or minimal changes. The HD cases were all clinically diagnosed, had a positive family history and showed the characteristic lesions in the caudate nucleus. The neuronal counts were compared with those in nine controls. In the granule cell layer of the dentate, CA3 and CA4, there was no significant difference in the neuronal numerical density between the three groups. A striking difference between the HIV and HD groups was seen in the CA1 region. The neuronal numerical density in the CA1 area was significantly lower in the HD patients than in either the HIV patients or the controls (mean (SD) 37.5 (5.0); 70.1 (13.4); 57.9 (15.4) x 10(3) per mm3, p < 0.001 (Students' t test)). This difference represents a neuronal loss of 35%. In all four hippocampal areas the neuronal density was higher in the HIV group than in the controls but the differences were not significant and can be explained by the higher average age of the control group. These findings contribute to the understanding of the mechanism of dementia in both AIDS and in Huntington's disease. PMID- 8505641 TI - MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. AB - Thirty eight patients with neurofibromatosis 1 (NF1) had neurological examinations, intellectual assessments and MRI scans. Increased intensity lesions on T2 weighted images were found in 13 patients. These abnormalities were more common in patients aged under 18 years. The lesions occurred predominantly in the basal ganglia, brainstem and cerebellum, and were multiple in 11 patients. They did not produce symptoms or neurological deficit in any patient and did not enhance with gadolinium-meglumine-triamine-pentaacetic acid contrast medium (Gd DTPA). In 2 patients, however, the abnormalities exerted mass effect distorting the brain and in 3 patients they occurred in conjunction with known gliomas. The lesions remained unchanged over a three year follow up period. The nature of the lesions is uncertain but the fact that they may produce mass effect and occur in association with gliomas suggests that they have malignant potential. There was no correlation between the presence of these abnormalities and intellectual impairment. PMID- 8505643 TI - Ocular and neurological Behcet's disease without orogenital ulceration? AB - A 28 year old West Indian patient is described who had a relapsing and remitting steroid-sensitive illness for 3 years. The clinical features included uveitis and widespread CNS involvement. The patient was treated as though he had neurosarcoidosis. Post mortem examination revealed histological changes compatible with a diagnosis of Behcet's disease, but at no time did he suffer from oral or genital ulceration or arthritis. The authors suggest a new term to encompass such an entity: the "Behcet's MINUS" syndrome (multifocal intermittent neurological and uveitic syndrome). PMID- 8505644 TI - Effect of intrathecal baclofen on the monosynaptic reflex in humans: evidence for a postsynaptic action. AB - Intrathecal baclofen is a very powerful antispastic agent. Its mechanism of action on the monosynaptic H-reflex in spinal patients was investigated. It could inhibit rapidly and profoundly monosynaptic reflexes in lower limbs, but did not modify Ia vibratory inhibition of the soleus H-reflex. To assess more precisely its effect on Ia afferents, an experimental paradigm using Ia heteronymous facilitation of the soleus H-reflex was used. Intrathecal baclofen did not modify the amount of monosynaptic facilitation of the soleus H-reflex brought about by stimulation of the femoral nerve. This demonstrates that the main part of the inhibitory effect of baclofen on the H-reflex in spinal patients is not due to a presynaptic effect, suggesting a postsynaptic site of action. PMID- 8505642 TI - Clinical implementation of anti-acetylcholine receptor antibodies. AB - A multivariate analysis of anti-acetylcholine receptor (AChR) antibodies and clinical parameters other than treatment (modified Osserman groups, age, type of onset, sex, and thymus pathology) was performed for all incident (n = 366) myasthenia gravis (MG) cases in its white population in Denmark during the past 15 years. Sera from 244 healthy individuals and from 295 patients with diseases other than MG were analysed as controls. Formal statistics for the anti-AChR antibodies assay (immunoprecipitation RIA using crude human AChR extract) were calculated. The distribution of antibodies titres greater than 0.1 nMole/l was found to be approximately lognormal. For MG patients the 95% reference interval was 0.2-1549 nMoles/l, and in control sera the range was 0.0-0.4 nMole/l. Using 0.5 nMole/l as the cut-off level and regarding all results less than this value as normal titres, it appeared that the assay was highly specific (> 99.99%) for MG. In a population of MG patients significance should be attributed to values in the range 0.3-0.4 nMole/l. The overall diagnostic sensitivity was found to be 88%. The sensitivity appeared to be proportionate to clinical severity of MG. The percentage with a normal titre was higher (16%) for early onset of MG, compared with 7% for late onset. No significant difference in relation to the frequency of "negative titre" was found in relation to sex. Anti-AChR antibodies titre was found to correlate with clinical severity, female or male gender, and pathology of thymus. The groups of MG patients were not matched for the various clinical parameters but multiple regression analysis controlling for these variables revealed independent effects of clinical severity and sex though not of age. Normal thymus (including involuted gland) and thymoma were correlated with low to intermediate tires, and hyperplastic thymus with high level of antibodies. The clinical implementation of anti-AchR antibodies is reviewed from 1976 and up to the present. The problems with false positive results are thoroughly expounded. PMID- 8505645 TI - The use of botulinum toxin in the treatment of adductor spasmodic dysphonia. AB - Botulinum toxin injections have been used to treat 31 patients with adductor spasmodic dysphonia. Injections of 3.00-3.75 units of botulinum toxin were performed bilaterally into the thyroarytenoid muscle. This treatment significantly decreased the standard deviation of the fundamental frequency of the speech sample, indicating a reduction in the variability of pitch amongst patients. A total of 96% of patients' subjective diary reports showed an improvement with a median of 7 days to peak effect and a 5 week duration of peak effect. PMID- 8505646 TI - The limitations of the tendon jerk as a marker of pathological stretch reflex activity in human spasticity. AB - The motor disorders associated with human spasticity arise, partly from a pathological increase in the excitability of muscle stretch reflexes. In clinical practice, reflex excitability is commonly assessed by grading the reflex response to a blow delivered to the tendon of a muscle. This is a much simpler response than the complex patterns of activity which may be elicited following muscle stretch caused by active or passive movement. Changes in the biceps brachii tendon jerk response have been followed over the first year after stroke in a group of hemiparetic patients and compared with changes in short and medium latency reflex responses elicited by imposed elbow flexion of initially relaxed spastic muscle and with the development of the late reflex responses which contribute to spastic hypertonia. A progressive increase in tendon jerk responses occurred over the first year following stroke, whereas reflex responses to imposed displacement, in particular the late reflex responses contributing to muscle hypertonia, reached their peak excitability one to three months after stroke, with a subsequent reduction in activity. The tendon jerk reflex therefore provides an incomplete picture of the pathological changes in the reflex responses in spasticity. PMID- 8505647 TI - N-hexane neuropathy in offset printers. AB - In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered. PMID- 8505648 TI - Subarachnoid haemorrhage in the elderly: a necropsy study of the association with cerebral amyloid angiopathy. AB - To clarify the contribution of cerebral amyloid angiopathy (CAA) to subarachnoid haemorrhage (SAH) in the elderly, relationships between SAH and CAA were investigated in 997 necropsy cases aged 60 years or older. Primary SAH (bleeding from subarachnoid vessels) was found in 15 cases (1.5%). There was no case in which primary SAH was clearly attributed to CAA. Secondary SAH [secondary rupture of intracerebral haemorrhage (ICH) through the cortex to the subarachnoid space] was found in 23 patients (2.3%). In 11 (48%) of them, ICH with secondary SAH was associated with CAA. The results indicated that primary SAH is rarely related to CAA, however, CAA is the most frequent cause of ICH accompanying secondary SAH in the elderly. PMID- 8505649 TI - Anorgasmia in anterior spinal cord syndrome. AB - Three male and two female patients with anorgasmia and dissociated sensory loss due to an anterior spinal cord syndrome are described. Clinical, neurophysiological and quantitative sensory evaluation revealed preservation of the large fibre dorsal column functions from the lumbosacral segments with concomitant severe dysfunction or absence of the small fibre neospinothalamic mediated functions. These findings indicate a role for the spinothalamic system in orgasm. PMID- 8505650 TI - Crossed avoiding reaction: a disturbance of the manual spatial function. AB - A patient with MRI confirmed lesions in the corpus callosum and the left cingulate gyrus had a rare syndrome of crossed avoiding reaction of the left hand. With the right hand she could reach a stimulus object in whatever space it was presented. With the left hand, however, she could not mobilise it to reach a stimulus presented in the right hemispace relative to her body axis. In the left hemispace relative to her body axis her left hand reached an object without any difficulty. This left unilateral difficulty in the right unilateral space may be related to a unique spatial function that controls manual space, which is represented differentially in the two hemispheres. In the left hemisphere this function covers bilateral hemispace and is operated by the right hand. In the right hemisphere this function covers only the left hemispace and is operated by the left hand. PMID- 8505651 TI - A clinical study of hypergraphia in epilepsy. AB - Fifteen patients with epilepsy and hypergraphia were compared with 32 patients with epilepsy but without hypergraphia. The number of previous psychiatric episodes, the number of Washington Psychosocial Seizure Inventory (WPSI) items indicating emotional maladjustment, and the number of CT scan abnormalities were significantly greater in the hypergraphic patients than in the non-hypergraphic patients. Cognitive performance, EEG laterality and the scores of WPSI items related to the psychological stress of seizures did not differ significantly between the two groups. Hypergraphia reflects changes in emotional responsiveness secondary to organic temporal lobe lesions. PMID- 8505652 TI - Intracranial tumours that mimic transient cerebral ischaemia: lessons from a large multicentre trial. The UK TIA Study Group. AB - The clinical records of patients withdrawn from the UK-TIA Aspirin Trial after identification of a brain tumour were reviewed. Certain features of transient focal neurological dysfunction were associated with an underlying brain tumour rather than transient ischaemia: a) focal jerking or shaking; b) pure sensory phenomena; c) loss of consciousness; d) isolated aphasia or speech arrest. In several patients the misdiagnosis occurred because these features were interpreted as the sequelae of previous ischaemic damage. When a transient focal neurological attack is associated with any of these features, a brain tumour must be considered. If patients later develop epilepsy the diagnosis of cerebral ischaemia should be reviewed. PMID- 8505653 TI - Mechanisms of carbamazepine-induced antidiuresis. PMID- 8505654 TI - Acute transient hydrocephalus in carbon monoxide poisoning: a case report. PMID- 8505655 TI - Pain arising from the oesophagus may mimic glossopharyngeal neuralgia. PMID- 8505656 TI - Predicting the outcome of acute stroke. PMID- 8505657 TI - Hypergraphia and brain damage. PMID- 8505658 TI - Polyglucosan bodies are not an unusual finding in temporal lobe epilepsy. PMID- 8505659 TI - The direction of scratch test. PMID- 8505660 TI - High casein-lactalbumin diet accelerates blood coagulation in rats. AB - This study investigates the influence of a high protein intake on normal hemostasis, fluid balance and organ growth. Adult rats were fed semipurified diets that contained either 18 or 56 g/100 g casein-lactalbumin for 2 wk, and the following functions were measured: food and water intake, weight gain, blood pressure, bleeding and clotting time, ADP-stimulated platelet aggregation, thrombin time, prothrombin time and partial thromboplastin time. Although food intake was depressed by the high protein diet, weight gain was not affected by the regimen. Water consumption, 24-h urine excretion and kidney weight were significantly greater in rats fed the high protein diet than in controls. High protein intake resulted in shorter barbiturate-induced sleeping time. Bleeding time and clotting time were significantly lower in rats fed the high protein diet for 7 d. However, heart rate, mean arterial pressure, plasma protein and osmolarity, platelet aggregation, prothrombin time, partial thromboplastin time and thrombin time did not differ significantly. Because a high protein intake caused rapid coagulation of blood in rats without affecting the activity of clotting factors, we suggest that this diet sensitized rats to factors that initiate clotting in vivo. PMID- 8505661 TI - Nucleotide supplements alter proliferation and differentiation of cultured human (Caco-2) and rat (IEC-6) intestinal epithelial cells. AB - The effect of exogenous nucleotides on the proliferation and differentiation of enterocytes was comparatively studied using a human colon tumor cell line (Caco 2) and a normal rat small intestinal crypt cell line (IEC-6). Caco-2 cells exhibited more active endogenous nucleic acid metabolism than did IEC-6 cells, as evidenced by greater cellular pools of nucleotides and their metabolites. To determine the supplemental nutritional effect of nucleotides, a mixture containing equal amounts (10 mg/L) of AMP, CMP, IMP, GMP and UMP was added to the culture medium. The results showed that a nucleotide supplement under normal culture conditions did not affect proliferation and differentiation of Caco-2 cells. In contrast, nucleotide supplements under normal culture conditions promoted proliferation of IEC-6 cells. The addition of nucleotides to the culture medium also enhanced differentiation of IEC-6 cells when grown on an extracellular matrix (Matrigel). Furthermore, when glutamine levels were less than optimal (nutritional stress conditions), nucleotide supplements enhanced growth and maturation of both cell lines. We conclude that the de novo biosynthesis of nucleotides is sufficient to support proliferation of tumor Caco 2 cells but not of the normal crypt IEC-6 cells. Thus, nucleotide supplements may enhance normal enterocyte growth and maturation as well as spare the need for exogenous glutamine in cell maintenance and development. PMID- 8505662 TI - Higher total energy expenditure contributes to growth faltering in breast-fed infants living in rural Mexico. AB - To investigate the energy requirements of infants living under unfavorable environmental conditions in rural Mexico, we measured the total energy expenditure (TEE) of 40 Otomi infants at approximately 4 or approximately 6 mo of age. Total energy expenditure was estimated by the doubly labeled water method: 100 mg 2H2O/kg and 250 mg 18O/kg were administered orally, after which urine was collected serially for 7 or 10 d. Isotopic enrichment of urine samples was analyzed by gas-isotope-ratio mass spectrometry. Weight and length were measured monthly from birth to 6 mo. Fat free mass was estimated from 18O dilution spaces. Total energy expenditures (mean +/- SD) were 310 +/- 58 and 318 +/- 29 kJ.kg-1 x d-1 at approximately 4 and approximately 6 mo, respectively. Total energy expenditure was higher than that previously observed for breast-fed infants reared under more protected environments (268 +/- 29 kJ.kg-1 x d-1). Weight, length and weight gain were 5.9 +/- 0.8 kg, 60 +/- 2 cm and 2.9 +/- 2.4 g.kg-1 x d-1 at 4.25 mo and 7.1 +/- 0.8 kg, 65 +/- 2 cm and 1.0 +/- 1.2 g.kg-1 x d-1 at 6.27 mo. Growth faltering was evident at 6 mo by clinically significant declines in growth velocities and National Center for Health Statistics Z-scores. Body fat of the Otomi infants averaged 21 +/- 6 and 18 +/- 5 g/100 g at approximately 4 and approximately 6 mo, respectively. Higher rates of TEE narrowed the margin of energy available for growth and thereby contributed to growth faltering in the Otomi infants. PMID- 8505663 TI - Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. AB - We studied physical fitness with the Harvard Step Test, growth, and appetite in primary school boys infected with hookworm (96% baseline prevalence), Trichuris trichiura (98% prevalence) and Ascaris lumbricoides (41% prevalence) who received a single 600-mg dose of albendazole or an identical placebo. Boys were examined, allocated at random within pairs by descending hookworm egg count to placebo (n = 26) or albendazole (n = 27) groups, treated, and re-examined 4 mo later. Four months after treatment, the albendazole group showed highly significant improvements in fitness score, resting heart rate, and heart rates at 1, 2, 3 and 4 min after the Harvard Step Test, whereas the placebo group had not changed significantly. The albendazole group also exhibited significantly more rapid growth judged by weight gain (1.0 kg greater than the placebo group, P < 0.0002), height increment (0.6 cm more, P < 0.003), arm circumference (0.3 cm more, P < 0.0002), and triceps and subscapular skinfolds (1.0 mm more, P < 0.0002), and showed improved appetite with objective and subjective measures. We conclude that single-dose treatment with albendazole can allow improved physical fitness, growth, and appetite in school-age children in areas where these helminths and poor growth are highly prevalent. PMID- 8505664 TI - Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. AB - The effect of dietary calcium on fecal fatty acid excretion and serum lipids was tested in a randomized, single-blind metabolic study in 13 healthy men with moderate hypercholesterolemia. A low calcium base diet containing 34% of energy from fat, 13% from saturated fatty acids, 240 mg cholesterol/d and 410 mg Ca/d was compared with a fortified version in which calcium citrate malate was added to orange juice, (550 mg) muffins (750 mg), and two tablets (500 mg) for a total calcium intake of 2200 mg/d. Fecal collections (72 h, d 8, 9, 10) and blood from fasting subjects for lipids and lipoproteins (d 9, 10, 11) were obtained. The percentage of dietary saturated fat excreted per day increased from 6 to 13% with calcium fortification. There was no change in fecal bile acid excretion. The high Ca diet significantly reduced total cholesterol 6% (5.99 to 5.66 mmol/L), LDL cholesterol 11% (4.13 to 3.67 mmol/L), and apolipoprotein B concentrations 7% when compared with the low Ca diet (P < 0.05). There was no change in HDL cholesterol or apolipoprotein A1 concentrations. Urinary calcium excretion increased from 146 to 230 mg/d when the high Ca diet was consumed. Calcium fortification was effective in lowering total and LDL cholesterol concentrations and may be an effective adjunct to cholesterol-lowering diet therapy. PMID- 8505665 TI - The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid. AB - The relative bioavailability of ascorbic acid from several sources was compared in 68 male non-smokers. Subjects underwent two 8-wk ascorbic acid depletion repletion cycles. In repletion, subjects were randomized to receive 108 mg/d ascorbic acid as tablets with or without iron, as orange segments or juice, or as raw or cooked broccoli with a crossover within each major treatment group (e.g., cooked to raw broccoli) for the second repletion. Relative ascorbic acid bioavailability was estimated based on the slope obtained from linear regression of plasma ascorbic acid on time during each repletion. In the first repletion, slopes for all groups were similar except for the group consuming raw broccoli (20% lower response, P < 0.01). Second repletion responses were attenuated, but were similar to the first repletion. Ascorbic acid ingested as cooked broccoli, orange juice or fruit, or in synthetic form seems to be equally bioavailable. The lower relative bioavailability of ascorbic acid from raw broccoli is unlikely to be of practical importance in mixed diets. PMID- 8505666 TI - Intestinal glucose absorption is lower in obese than in lean Zucker rats. AB - Obese Zucker (fa/fa) rats had lower intestinal glucose absorption following an intragastric [U-14C]glucose load than lean (+/?) Zucker rats. In the fa/fa animals, the rate of oxidation of the tracer to 14CO2 was similar to that observed in their lean counterparts. Although there were no differences in the incorporation of the tracer in liver and skeletal muscle glycogen, the conversion and incorporation of [U-14C]glucose into tissue [14C]lipid was higher in the obese animals. Isolated enterocytes from lean and obese Zucker rats showed a similar capacity for [U-14C]glucose utilization. Reconstituted brush border membrane vesicles from obese Zucker rats showed a higher Vmax for glucose transport than those from their lean counterparts. The lower glucose absorption found in the fa/fa rats in vivo may contribute to the maintenance of normoglycemia in these animals. PMID- 8505667 TI - Oxidative stress may contribute to the intestinal dysfunction of weanling rats fed a low protein diet. AB - Intestinal function is impaired in malnutrition. Because oxidative stress is a component of gastrointestinal injury, and malnutrition may reduce antioxidant defenses, we investigated the involvement of oxidative stress in the intestinal dysfunction due to malnutrition. Weanling rats were fed either a normal protein (22% casein) or a low protein (6% casein) diet for 4 wk. In intestinal homogenates, we assessed free radical damage and enzymatic antioxidant defenses. In jejunal fragments mounted in Ussing chambers, we measured ionic transport by short-circuit current (Isc) and protein permeability by transepithelial fluxes of beta-lactoglobulin. Catalase activity and the thiobarbituric acid-reacting substances concentration were greater in intestinal mucosa of the low protein group, whereas the glutathione concentration and the activities of superoxide dismutase and Se-dependent glutathione peroxidase were the same as in the normal protein group intestinal mucosa. Both basal Isc and the delta Isc induced by glucose and forskolin, as well as beta-lactoglobulin fluxes, were higher in the low protein group. Exogenous H2O2 stress increased Isc significantly more in the low protein than the normal protein group but did not alter protein permeability. These results show that malnutrition induces both intestinal free radical damage and altered epithelial transport, suggesting that oxidative stress may contribute to the intestinal dysfunction associated with malnutrition. PMID- 8505668 TI - Evaluation of the arteriovenous difference technique to simultaneously estimate protein synthesis and degradation in the hindlimb of fed and chronically underfed steers. AB - Our objectives were to validate a technique to measure protein turnover based on net fluxes of tyrosine radioactivity and mass across the hindlimb, and to describe the impact of nutrition on hindlimb protein kinetics and nutrient utilization in growing Holstein steers. External iliac vessels were catheterized to allow for measurements of hindlimb arteriovenous (AV) differences and blood flow. Animals were used in a single reversal design with 16-d periods. Treatments were either 60% (0.6M) or 220% (2.2M) of the energy required for maintenance. On d 12 and 14 of each period, a primed-continuous infusion of L-[side chain-2,3 3H]tyrosine was initiated, followed by a 4-h sampling period to assess hindlimb nutrient utilization and protein kinetics. Well-fed steers exhibited rates of hindlimb utilization for non-nitrogenous energy substrates and amino acids that were consistent with values previously reported for well-fed ruminants. Underfeeding decreased hindlimb blood flow (62%), oxygen consumption (51%) and utilization of respiratory fuels (64-73%). Protein synthesis was also reduced (49%), leading to net nitrogen loss from the hindlimb. The estimated energy cost of protein synthesis accounted for 13% of hindlimb oxygen consumption across intake levels. Hindlimb protein balance was consistent with whole-body balance, adding credence to derived rates of degradation. Overall, data support the validity of the AV difference technique to estimate components of hindlimb protein turnover. PMID- 8505669 TI - Folate catabolism is increased during pregnancy in rats. AB - The hypothesis examined in the present study is that pregnancy results in a greater rate of folate catabolism. Mammalian folate catabolism proceeds by cleavage of the vitamin at the C9-N10 position to yield p-aminobenzoylglutamate, which is quantitatively excreted in the urine after its acetylation. A recently developed HPLC method for the determination of endogenous levels of this catabolite, acetamidobenzoylglutamate, in rat urine was used to investigate folate catabolism in three groups of female rats (n = 6/group), one nonpregnant and two pregnant groups. One of the pregnant groups was allowed to feed freely whereas the other was pair-fed to the nonpregnant control group. The daily excretion of acetamidobenzoylglutamate was stable in the nonpregnant group over the experimental period but increased significantly with progression of gestation in both pregnant groups, in which values peaked at d 18 to concentrations of up to three times those of the nonpregnant animals. In both pregnant groups the values fell significantly before parturition, demonstrating that increased catabolism of folate is a feature of pregnancy per se and not simply due to increased weight. These results suggest that increased catabolism may make an important contribution to the folate deficiency associated with pregnancy. PMID- 8505670 TI - White wheat flour lowers plasma cholesterol and increases cecal steroids relative to whole wheat flour, wheat bran and wheat pollard in rats. AB - Plasma cholesterol concentrations were significantly lower in rats fed a cholesterol-free diet containing white wheat flour than those fed the diet with whole wheat or wheat bran. Concentrations of total bile acids and neutral sterols in cecal digesta were significantly higher in rats fed wheat flour than in those fed whole wheat, wheat pollard or wheat bran. Digesta bile acids and neutral sterol pools correlated negatively with plasma cholesterol, indicating that excretion was regulating plasma concentration. Total cecal volatile fatty acid (VFA) concentrations were unaffected by diet but cecal propionate was higher and butyrate lower in rats fed wheat flour than in those fed whole wheat. Cecal digesta butyrate concentrations correlated negatively with the cholesterol metabolite, coprostanol, and with secondary bile acids. Cecal propionate correlated negatively with plasma cholesterol concentration, but butyrate correlated equally positively, suggesting these VFA were indicators rather than regulators of altered cecal steroid metabolism. Effects of white wheat flour on steroid metabolism and cecal VFA resemble those of oat bran and support the observation that wheat flour might be hypocholesterolemic in humans. PMID- 8505671 TI - Urinary excretion of deuterium-labeled folate and the metabolite p aminobenzoylglutamate in humans. AB - Stable isotopic methods were employed to determine the proportion of ingested folate excreted as the metabolite p-aminobenzoylglutamate (pABG, free and N acetyl) in urine. Adult male subjects (n = 7) were maintained on a 4.54 mumol/d (2 mg/d) folate saturation regimen. After 7 d, subjects were given a mixed oral dose containing 0.67 mumol (300 micrograms) each of bideuterofolic acid (d2) and tetradeutero-folic acid (d4). Urine was collected for the following 48 h and analyzed for folate and pABG. The extent of deuterium labeling of urinary folate and pABG was determined by gas chromatography-mass spectrometry. Urinary total pABG excretion increased less than twofold as a result of the folate saturation, whereas urinary folate increased over 10-fold. Urinary d2 and d4 folates each contained 14-15% of the respective oral doses of labeled compounds, whereas urinary d2 and d4 pABG comprised only 0.98-1.15% of the labeled doses. Molar ratios (d2/d4) of excreted folate and pABG indicated that there was no in vivo isotopic discrimination between the labeled folates. Urinary pABG accounted for 5.1 +/- 0.6% of total ingested folate, whereas labeled pABG was about 6.7-7.6% of the excretion of labeled compounds (i.e., labeled folate + pABG). This study indicated that pABG is not a major excretory product during folate supplementation, but its relative importance may increase in conditions of reduced folate nutriture. PMID- 8505672 TI - Excess dietary lysine increases skeletal muscle and plasma trimethyllysine in rats. AB - Trimethyllysine, a carnitine precursor, is a cation. This study was designed to determine whether dietary potassium and lysine concentration or oral lysine supplementation affects tissue carnitine and trimethyllysine concentration in rats. In Experiment 1, rats were fed a control diet, a low or high potassium diet, or a high lysine diet. In Experiment 2, rats were given by gavage a solution containing either L-proline (control) or L-lysine. In Experiment 1, rats fed the high lysine diet had significantly lower plasma total carnitine concentration than controls. Rats fed the high lysine diets had significantly higher concentrations of free trimethyllysine in skeletal muscle and plasma relative to control rats and rats fed the high potassium diet. Rats fed the low potassium diet had a similar increase in skeletal muscle free trimethyllysine. In Experiment 2, rats given lysine had significantly lower plasma total carnitine concentration, and significantly greater skeletal muscle and plasma trimethyllysine concentration relative to controls. We conclude that dietary potassium and lysine, and oral lysine, have a significant effect upon the distribution of carnitine and trimethyllysine in rats. The distributional changes caused by lysine, however, seem to be due to effects other than exchange of lysine for carnitine or trimethyllysine in tissues. PMID- 8505673 TI - Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. AB - The nutritional requirement of selenium for type I 5'-deiodinase activity in thyroid compared with liver was assessed in rats. Male weanling Sprague-Dawley rats were fed a torula yeast-based diet for 20 wk. One group of rats was fed the Se-deficient basal diet (0.01 mg Se/kg). The other three groups were fed the basal diet plus sodium selenite at 0.05, 0.1 and 0.5 mg Se/kg diet. Liver 5' deiodinase and glutathione peroxidase (GSH-Px) activities were depressed in the group fed the Se-deficient (basal) diet compared with the other groups. Liver 5' deiodinase activity in the group fed 0.05 mg Se/kg diet was as high as in the groups fed 0.1 and 0.5 mg Se/kg diet, whereas GSH-Px activities in the groups fed 0.05 and 0.1 mg Se/kg diet were intermediate in value. Feeding the Se-deficient diet for 20 wk did not cause a suppression in 5'-deiodinase in the thyroid, and thyroid GSH-Px activity was approximately 40% of that in the other groups. In rats fed Se-supplemented diets, thyroid GSH-Px was approximately 20% or less of the activity found in liver. Plasma thyroxine was higher in the group fed the Se deficient (basal) diet, but there were no differences in plasma 3,3',5 triiodothyronine among all groups. The results suggest that the nutritional Se requirement for 5'-deiodinase is less than that for GSH-Px and is approximately 0.05 mg Se/kg in the diet for normal activity in the liver and approximately 0.01 mg Se/kg for normal activity in the thyroid. Thyroid seems to be a priority organ over liver for Se when the intake of the element is limited. PMID- 8505674 TI - The ferret as a model for evaluation of the bioavailabilities of all-trans-beta carotene and its isomers. AB - The objective was to develop the ferret as a model for evaluation of the bioavailabilities of natural and synthetic beta-carotenes in foods. For these studies, a low carotenoid purified diet was formulated that produced excellent food intake and adequate growth. After consuming the diet for 16 d, ferrets were randomly assigned to one of three groups. For a 10-d period, they ingested a standardized amount of all-trans-beta-carotene (18 mumol/L) from either carrot juice, a test beverage of beta-carotene beadlets dispersed in fruit juices, or a control beverage of beta-carotene beadlets dispersed in water. Accumulations of all-trans-beta-carotene in the sera, livers and adrenals of ferrets that consumed the carrot juice were significantly lower (P < 0.02) compared with those of ferrets that consumed the test or control beverages. The content of a cis-isomer component relative to that of all-trans-beta-carotene was higher in each beta carotene beadlet-fortified beverage than in the liver and adrenal tissues of ferrets that ingested the beverage; the cis-isomer was not measurable in sera. The content of all-trans-beta-carotene relative to that of all-trans-alpha carotene, a structural isomer, was higher in carrot juice than in sera of ferrets that ingested the juice. We conclude that: 1) all-trans-beta-carotene is less bioavailable from carrot juice than from beta-carotene beadlet-fortified beverages, and 2) there are apparent bioavailability differences between isomers of beta-carotene in ferrets. PMID- 8505675 TI - Diets containing corn oil, coconut oil and cholesterol alter ventricular hypertrophy, dilatation and function in hearts of rats fed copper-deficient diets. AB - Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P < 0.05) LV free wall width, regardless of dietary fat type, and greater intraventricular septum width in the rats fed corn oil. Rats fed the copper deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction. PMID- 8505676 TI - Feeding medium-chain triglycerides to rats decreases degradation of sucrase isomaltase complex in the jejunum. AB - We demonstrated previously that feeding a diet containing medium-chain triglycerides (MCT) to rats causes an increase in the sucrase activity in jejunum relative to diets containing long-chain triglycerides (LCT). To explore the mechanism whereby MCT affect jejunal sucrase activity, 7-wk-old rats were fed a high LCT diet for 7 d, and then they were force-fed either the high LCT diet, a high MCT diet or a high carbohydrate (alpha-methylglucoside) diet for the subsequent 12 h. Feeding the high carbohydrate diet produced significantly greater sucrase and isomaltase activities in both upper and lower jejunum than feeding the LCT diet. Feeding the high MCT diet led to significantly greater sucrase activity in the lower jejunum, but isomaltase activity was not elevated. Rocket immunoelectrophoresis revealed that in the lower jejunum of the rats fed the high MCT diet the proportion of sucrase-isomaltase complex to its degradation product (i.e., isomaltase monomer) was elevated, suggesting that dietary MCT affects sucrase activity by retardation of degradation of sucrase-isomaltase. Because the amounts of total bile acids in the upper jejunum were 50% lower in rats fed the high MCT diet relative to animals fed the high LCT diet, it is likely that MCT feeding decreases secretion of bile into the lumen, which in turn decreases degradation of the sucrase subunit of the sucrase-isomaltase complex. PMID- 8505677 TI - Elevated neuropeptide Y in the arcuate nucleus of young obese Zucker rats may contribute to the development of their overeating. AB - Neuropeptide Y (NPY) mediates feeding behavior through a local hypothalamic network formed by the arcuate and paraventricular nuclei (the AP axis). In the hypothalamus, NPY is mainly synthesized in neurons of the arcuate nucleus. These neurons project to the paraventricular nucleus, the site where NPY has the strongest stimulatory effects on food intake of Sprague-Dawley rats. In the adult Zucker fatty rat (a genetic model of obesity with a well-established hyperphagia), NPY concentrations in these nuclei are higher than in its lean counterpart. We measured hypothalamic NPY before the appearance of altered eating behavior, e.g., in very young (16-d-old) lean and obese Zucker pups, and in pups at an age when overeating had begun, e.g., a few days after weaning at 30 d. At 30 d, NPY concentrations were significantly higher in obese than in lean rats in the arcuate nucleus (14.2 +/- 0.7 vs. 11.6 +/- 0.5 pmol/mg protein, P < 0.01). This difference was not observed at 16 d. A 160% increase was noted in the paraventricular nuclei of obese rats between 16 and 30 d of life compared with a 100% increase in the lean rats (P < 0.001). Neuropeptide Y concentration was greater in 30-d-old rats than in 16-d-old rats in other areas involved in the regulation of feeding behavior, such as the dorsomedian nuclei and lateral hypothalamus, but the values did not differ between genotypes. Higher NPY concentration was therefore detected early in young obese rats in the main hypothalamic site of NPY synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505678 TI - Roundtable discussion on milkfat, dairy foods, and coronary heart disease risk. AB - A group of 12 research scientists participated in a roundtable discussion on the health implications of milkfat in balanced diets. Four subjects areas were addressed: contributions of dairy foods and other fat sources to diets in the United States; influence of individual fatty acids on coronary heart disease risk; dairy foods and coronary heart disease risk; and health implications of low fat diets. The purpose of the meeting was twofold. First, the researchers evaluated the impact of fatty acids, milkfat and dairy foods on coronary heart disease risk, based on currently available evidence. They met this objective by considering statements of "fact" that were accepted, modified or rejected upon discussion. Final statements are presented in this report. Second, the group identified research questions that must be addressed to better define the role of dietary fats (in general) and milkfat (in particular) in varied diets. Critical study design considerations were high-lighted. Participants agreed that standard fat dairy foods can fit into diets meeting contemporary fat intake guidelines; the guiding principles of balance, variety and moderation were stressed. More research is needed to understand fully the impact on blood lipid profiles (and on other indicators of disease risk) of butter and other sources of milkfat in mixed fat diets. PMID- 8505679 TI - Chemical modifications of proteins in vivo: selected examples important to cellular regulation. AB - The synthesis and degradation pathways for individual proteins and functional peptides often involve numerous co- and post-translational modifying steps. This review focuses on the diversity of such reactions. The reactions are organized into functional categories. An overall goal is to highlight post-translational events as often having the same importance to functional protein production as the transcriptional and translational events that initiate their synthesis. PMID- 8505680 TI - Estimated prevalences of panic disorder and depression among consecutive patients seen in an emergency department with acute chest pain. AB - OBJECTIVE: 1) To determine whether the frequencies of panic disorder (PD) and depression (DEP) in an emergency department (ED) population were comparable to those in other primary care groups; 2) to evaluate whether patients without the clinical diagnosis of acute cardiac ischemia (ACI) had higher frequencies of these disorders; and 3) to identify characteristic clinical findings in patients with PD or DEP. SETTING: An urban teaching hospital ED. PATIENTS: Three hundred thirty-four patients with acute chest pain were evaluated prospectively over an eight-week period. The cohort participating (69%-229/334) completed psychiatric screening measures, including the Panic Disorder Self-Rating Scale, the Beck Depression Inventory, and the Zung Self-Rating Anxiety Scale. MEASUREMENTS AND MAIN RESULTS: A symptom profile consistent with PD was identified in 17.5% of the patients (40/229), DEP in 23.1% (53/229), and either disorder in 35% (80/229). The prevalences of PD were similar in those with and without ACI (19.4% vs 16.6%, respectively, p > 0.05). The likelihoods of one or more ED visits for chest pain in the previous year were significantly greater in those with PD (57.5% vs 36%, p < 0.05) and DEP (54% vs 35%, p < 0.05) than in those without these psychiatric disorders. CONCLUSION: This study suggests that approximately one in three patients presenting to the ED with acute pain has symptoms consistent with a psychiatric disorder. These disorders occur frequently in both those with and those without acute cardiac ischemia, and clinical variables may help identify these frequent ED utilizers. PMID- 8505681 TI - Detection of bulimia in a primary care setting. AB - OBJECTIVE: To develop a screening tool for the identification of bulimia in ambulatory practice. DESIGN: Administration of a 112-item questionnaire about eating and weight-control practices to women with known bulimia and to healthy control patients. Questions were compared with DSM-III-R criteria of bulimia as a "gold standard." SETTING: Self-help group for eating disorders and hospital-based primary care practice. SUBJECTS: Thirty of 42 women with known bulimia met DSM III-R criteria for current bulimia, and 124 of 130 control patients met the criterion of no history of an eating disorder. MAIN RESULTS: Thirteen individual questions discriminated between bulimic subjects and control subjects with a sensitivity and specificity of > 75%. When these questions were entered into a stepwise logistic model, two questions were independently significant. A "no" response to the question "Are you satisfied with your eating patterns?" or a "yes" response to "Do you ever eat in secret?" had a sensitivity of 1.00 and a specificity of 0.90 for bulimia. The positive predictive value, based on a 5% prevalence, was 0.36. CONCLUSIONS: A set of two questions may be as effective as a more extensive questionnaire in identifying women with eating disorders, and could be easily incorporated into the routine medical history obtained from all women. PMID- 8505682 TI - Exercise counseling: how do general internists do? AB - OBJECTIVE: To assess how often physicians counsel patients about exercise and to identify which primary care internists infrequently counsel about it. DESIGN: Cross-sectional survey of a random sample of primary care internists in Massachusetts. Questions covered physicians' attitudes, beliefs, and practices with respect to counseling about exercise; physicians' perceived barriers to counseling about exercise; physicians' personal exercise frequency; and physician demographics. PARTICIPANTS: Of 1,000 physicians, 687 were eligible and 422 returned usable questionnaires (response rate 61%). RESULTS: Data describing physician demographics, practice setting, measures of personal fitness, and beliefs regarding exercise were entered into a logistic regression model. The characteristic that best identified physicians who infrequently counsel about exercise was their perceived lack of success at counseling (OR 22.83, 95% CI 8.36 62.31). Other independent predictors of infrequent counselling were physicians' lack of conviction that exercise is very important (OR 4.86, 95% CI 1.70-13.91), physician age < or = 40 years (OR 3.08, 95% CI 1.33-7.15), and higher physician resting heart rate (OR 3.45, 95% CI 1.46-8.18). CONCLUSIONS: Several factors were found to be independently associated with the likelihood of a physician's counseling about exercise. These included physician perceived success at counseling, physician belief that exercise is important, physician age, and physician resting heart rate. These results suggest possible strategies to improve physician's counseling efforts. PMID- 8505683 TI - What do applicants look for when selecting internal medicine residency programs? A comparison of rating scale and open-ended responses. AB - OBJECTIVE: To develop reliable scale measures of factors most important to applicants when they select internal medicine residencies and to assess their validity by comparing scores from these measures with responses to open-ended questions. DESIGN: All 353 applicants ranked by the University of North Carolina at Chapel Hill (UNC-CH) for the 1988 National Residency Match Program received a questionnaire after submitting their match lists. First, they listed the three most important factors considered in ranking residency programs and starred the single most important factor out of the three. Then, they rated 41 items on a five-point Likert scale ranging from 1 (not important) to 5 (extremely important). SETTING: Categorical internal medicine residency program at an academic medical center. MEASUREMENTS AND MAIN RESULTS: 315 (88%) applicants responded to the survey. Three reliable scales, Interpersonal Issues (7 items, alpha = 0.78), Reputation (5 items, alpha = 0.77), and Work Issues (11 items, alpha = 0.89), were developed using exploratory factor analysis of applicants' responses to the 41 items. Applicants felt interpersonal issues were very important (mean score = 4.2 +/- 0.5), academic reputation was important (3.3 +/- 0.8), and work issues were less important (2.8 +/- 0.7). The differences between these scores were significant (F = 3.76, p < 0.05). The ratings for the top five items not in these scales also indicated that education and location were very important. These results were corroborated by applicants' responses to the open ended request to list the three most important factors in ranking residencies. CONCLUSION: These findings suggest that work issues are important, but greater emphasis is placed on interpersonal issues, education, location, and a program's reputation when applicants select residency programs. Furthermore, this study provides evidence supporting the reliability and validity of the three scales. PMID- 8505684 TI - How reliable is peer review of scientific abstracts? Looking back at the 1991 Annual Meeting of the Society of General Internal Medicine. AB - OBJECTIVE: To evaluate the interrater reproducibility of scientific abstract review. DESIGN: Retrospective analysis. SETTING: Review for the 1991 Society of General Internal Medicine (SGIM) annual meeting. SUBJECTS: 426 abstracts in seven topic categories evaluated by 55 reviewers. MEASUREMENTS: Reviewers rated abstracts from 1 (poor) to 5 (excellent), globally and on three specific dimensions: interest to the SGIM audience, quality of methods, and quality of presentation. Each abstract was reviewed by five to seven reviewers. Each reviewer's ratings of the three dimensions were added to compute that reviewer's summary score for a given abstract. The mean of all reviewers' summary scores for an abstract, the final score, was used by SGIM to select abstracts for the meeting. RESULTS: Final scores ranged from 4.6 to 13.6 (mean = 9.9). Although 222 abstracts (52%) were accepted for publication, the 95% confidence interval around the final score of 300 (70.4%) of the 426 abstracts overlapped with the threshold for acceptance of an abstract. Thus, these abstracts were potentially misclassified. Only 36% of the variance in summary scores was associated with an abstract's identity, 12% with the reviewer's identity, and the remainder with idiosyncratic reviews of abstracts. Global ratings were more reproducible than summary scores. CONCLUSION: Reviewers disagreed substantially when evaluating the same abstracts. Future meeting organizers may wish to rank abstracts using global ratings, and to experiment with structured review criteria and other ways to improve raters' agreement. PMID- 8505685 TI - Outpatients' attitudes and understanding regarding living wills. AB - OBJECTIVE: To assess outpatients' attitudes toward and understanding of a standard living will. DESIGN: Survey using a self-administered questionnaire that patients completed after they had read a sample living will. SETTING: General medicine clinic of a Department of Veterans Affairs medical center. PATIENTS: Two hundred fourteen patients (85% of those approached) attending a continuity care clinic appointment. Eighty-seven percent were men; mean age was 60 years. MEASUREMENTS AND MAIN RESULTS: Patients' attitudes toward living wills, understanding of the terminology contained in living wills, desire to discuss living wills with their doctors, and desire to prepare a living will. RESULTS: Seventy-two percent of the patients had prior knowledge of living wills, though only 53% had discussed the topic with family members and only 14% with physicians. Half felt that the living will terminology should be simplified, and 55% were unable to identify the correct definition for at least one commonly used term. Desire to prepare a living will was positively associated with better understanding of the sample document and previous knowledge of and exposure to living wills, and was negatively associated with concern about its use and revocability (all p < 0.001). Patients who reported poor understanding of the living will were more likely to want to discuss the topic with a physician (p < 0.01). CONCLUSIONS: In this ambulatory patient population attitudes toward living wills were influenced by knowledge and understanding of these documents. Primary care physicians and institutions should develop patient education strategies that enhance understanding of advance directives. PMID- 8505686 TI - Intensive one-week orientation for foreign medical graduates entering an internal medicine residency program. AB - The authors describe an intensive week-long introduction to hospital-based medical practice for foreign medical graduates (FMGs) entering an internal medicine residency program. The intensive orientation helps the FMGs function more effectively in the American hospital environment and reduces the frequency of personal and professional adjustment problems. The program is easily adaptable to other hospitals with large numbers of FMG residents. PMID- 8505687 TI - Substance abuse and AIDS: a faculty development program for primary care providers. AB - The authors implemented a three-day faculty development program on substance abuse and AIDS for primary care faculty. Objectives included: 1) increased knowledge concerning clinical issues; 2) skill development focusing on provider patient interactions; and 3) the development of educational approaches for teaching about substance abuse and AIDS. Teaching formats included didactic (40%) and experimental (60%) sessions emphasizing role playing with patients affected by both substance abuse and HIV infection. Four courses have been given to 109 participants, who have rated the course highly in terms of its educational quality (4.4/5.0) and usefulness (4.2/5.0). At six-month follow-up, 75% of the participants reported enhanced teaching as a result of this faculty development program. PMID- 8505688 TI - Outpatient evaluation of obesity in adults and children: a review of the performance of internal medicine/pediatrics residents. AB - A chart audit of 115 adults and 113 children seen consecutively in an internal medicine/pediatrics residency was conducted to assess recognition of obesity and appropriateness of suggested therapy. Patients were categorized as obese, overweight, or normal based on body mass index. Forty-four percent of the children and 50% of the adults were classified as overweight or obese. Residents were more likely to document obesity in adults (53%) than in children (18%, p < 0.0001). Higher degree of obesity in adults increased resident documentation of the condition (p = 0.022), but presence of additional cardiovascular risk factors did not. When overweight or obesity was recognized, residents chose appropriate therapy. Enhanced education to improve recognition of obesity appears warranted. PMID- 8505689 TI - Noninvasive imaging of the lower extremity for deep venous thrombosis. AB - Noninvasive imaging for LE DVT has advanced remarkably in the past decade. Currently, IPG and ultrasound techniques (RTU and DS) have been proven to be quick, accurate, relatively inexpensive, and widely available methods for detecting proximal LE DVT and can be used as the initial diagnostic studies in many settings. Color-flow Doppler ultrasound studies may be more accurate than other ultrasound techniques in diagnosing calf DVT and in differentiating acute from chronic LE DVTs, though this bears further review. Many concerns remain regarding noninvasive LE DVT imaging, including: The accuracy of the above studies in nonreferral centers. The need for and optimal frequency of follow-up studies to detect clots that propagate proximally. The optimal noninvasive techniques for imaging in the setting of recurrent DVT and other specialized settings (e.g., high-risk patients). PMID- 8505690 TI - Polypharmacy: the cure becomes the disease. AB - Polypharmacy occurs when a medical regimen includes at least one unnecessary medication. Factors that contribute to this problem include: patient characteristics of increasing age, multiple medical problems, therapy expectations, and decisions to self-treat; physician factors such as excessive prescribing; and system problems of multiple providers and lack of a coordinating provider. Complications include increased adverse drug reactions and noncompliance, which can lead to increased hospitalization and associated costs. Polypharmacy can be avoided by patient education and sharing the decisions for making the treatment goals and plan. The medication regimen can be simplified by eliminating pharmacologic duplication, decreasing dosing frequency, and regular review of the drug regimen. The goal should be to prescribe the least complex drug regimen for the patient as possible, while considering the medical problems and symptoms and the cost of therapy. PMID- 8505691 TI - Panic disorder and depression in emergency department chest pain patients. PMID- 8505692 TI - Requiring the autopsy. PMID- 8505693 TI - Automated latex nephelometric immunoassay for the measurement of serum lipoprotein (a). AB - A sensitive immunoassay based on latex particle agglutination has been developed for measuring lipoprotein Lp(a) concentrations in serum or plasma. Carboxylated latex particles (diameter 240 nm) covalently coated with F(ab')2 fragments of anti-lipoprotein Lp(a) antibodies are incubated with diluted sample (400-fold) for 12 min at room temperature, with the resulting agglutination quantified by measuring the change of light-scatter produced. The assay has been automated on the Behring nephelometer analyzer with a sampling rate of 150 samples/hour. This assay generates a standard curve in the range of 27 to 1750 mg/L, showing inter assay precision of less than 8%. There were no interferences from plasminogen, bilirubin, Intralipid, haemoglobin, rheumatoid factor, and apolipoprotein B. No significant differences were observed when fresh and frozen samples were compared. Sample pretreatment with "Lipoclean" clearing agent and sample lyophilization decreased the agglutinating reaction. In two separate studies using 77 and 112 patient sera the Lp(a) values, determined by the latex nephelometric method, the Terumo Macra Lp(a) ELISA test, and the Pharmacia Apo(a) radioimmunoassay method, gave correlation coefficients of 0.948 and 0.974, respectively. Physiological lipoprotein (a) values were determined in a blood donor group, with the distribution of serum Lp(a) highly skewed, with a mean (SD) and median values of 213(236) mg/L and 116 mg/L, respectively. Concentrations of Lp(a) were found to be age- and sex-independent. This latex nephelometric procedure is a convenient method and an interesting alternative to other immunoassays for routine measurement of human lipoprotein (a). PMID- 8505695 TI - Heat inactivation of bovine serum used for blockade in immunoenzymatic assay is associated with spurious fall on the titers of anticardiolipin antibodies in primary antiphospholipid syndrome sera. AB - Anticardiolipin antibodies (ACA) were evaluated using enzyme-linked immunosorbent assay (ELISA) with and without heat inactivation of bovine serum used for plastic surface blockade. Untreated sera samples from primary antiphospholipid syndrome patients (PAS) and healthy blood donors (HBD) were tested. A significant decrease of ACA titers of PAS sera occurred with inactivated bovine serum blockade ELISA when compared with basal ELISA. In HBD sera there was no significant change. Probably, as happens with normal human serum, heating for normal bovine serum produces an increase in ACA titers. This bovine ACA may react with cardiolipin, and when human samples are added, they find antigen sites occupied, resulting in a spurious decrease of ACA titers. PMID- 8505694 TI - The levels of serum myoglobin in cardiac patients with elevated creatine kinase MB and suspected acute myocardial infarction. AB - A monoclonal antibody enzyme immunoinhibition assay was used to quantitate serial serum myoglobin (Mb) levels in 121 patients who had > or = 5% creatine kinase-MB (CK-MB) and suspected acute myocardial infarction (AMI). Serum Mb levels higher than 0.16 micrograms/ml were considered abnormal. In 94% of these patients who were finally diagnosed with AMI, Mb levels were higher than 0.16 micrograms/ml, whereas all 30 normal control blood donors had lower Mb levels. Patients with anterior or inferior wall infarcts had higher Mb levels (> or = 0.64 micrograms/ml) than patients with lateral or subendocardial infarction. Only 68% (82/121) of patients evaluated by elevated CK-MB alone had a final diagnosis of AMI. In contrast, 94% (77/83) of patients who in addition showed elevated Mb had AMI. It is suggested that analysis of Mb levels allows a more accurate diagnosis of AMI in patients with elevated CK-MB than does reliance on CK-MB values alone. PMID- 8505696 TI - Flow karyotype analysis and sorting of the Chinese hamster chromosomes: comparing the effects of the isolation buffers. AB - The effects of different swelling solutions on the univariate flow karyotype of whole chinese hamster embryo cells (WCHE K10) and cloned chinese hamster embryo fibroblast cells (CCHE 40) were compared using four methods of chromosome isolation. Chromosomes of each cell line were prepared by the Aten, Polyamine Digitonin, Tris-Triton, and HEPES methods and analyzed with a FACStar flow cytometer. Polyamine-Digitonin and Aten methods produced the most satisfactory flow karyotype. Structurally aberrant chromosomes in the cell lines were detected in the flow karyotype as extra peaks. CCHE 40 chromosomes 1,2,X and 3q were sorted into separate tubes and reanalyzed; and the coefficient of variation of each chromosome peak was near 5%. To apply the flow karyotype analysis to clinical cytogenetics, chromosome preparation was one of the most important factor, and it is necessary to sort the chromosome peak sharply. PMID- 8505697 TI - Quick assay of serum HBs antibody levels using latex agglutination-integrating sphere turbidimetric assay (ISTA). AB - A method for determining serum HBs antibody applying the principle of integrating sphere turbidimetric assay (ISTA) by latex agglutination was developed. The minimum detectable level of HBs antibody by this method is 12.5 IU/L, indicating that this method is 3 times or more sensitive with better reproducibility and specificity than the passive hemagglutination (PHA) method. With a cut-off level of 25 IU/L, the possible highest simultaneous reading by this method was 1,000 IU/L. Serum HBs antibody can be readily measured in 10 or so minutes by this method if a fully automated EL-1000 analyzer is used. This rapid and simple method for determining serum HBs antibody will be useful not only clinically, but also in preventive medicine. PMID- 8505698 TI - Enzyme immunoassay for respiratory syncytial virus: rapid detection in nasopharyngeal secretions and evaluation of isolates representing different RSV subgroups. AB - The presence of respiratory syncytial virus (RSV) was investigated by immunofluorescent antibody (IFA) technique and by an enzyme immunoassay (EIA) in 169 samples of nasopharyngeal secretions of infants and children with acute respiratory infections. Of 31 samples positive by EIA, 25 were positive by IFA. In 24 samples from a retrospective study, RSV positive by IFA and/or tissue culture isolation (TCI), 22 were also positive by EIA. The EIA was also evaluated with 111 RSV isolates in Hep2 cell cultures representing different RSV subgroups. All were positive by EIA. PMID- 8505699 TI - Marking characteristics of anti-nuclear matrix protein NM200.4 in human breast carcinomas and normal human tissues. AB - Nuclear matrix proteins are a group of recently described proteins that are thought to be cell-type specific. Using a monoclonal antibody (NM 200.4; Matritech, Cambridge, MA) generated against nuclear matrix proteins isolated from a human breast carcinoma cell line, we examined frozen tissue sections from 30 breast carcinomas, and a variety of normal tissues to determine the antibody specificity, and to assess the relationship with the staining pattern and tumor type and hormone receptor status. Most breast carcinomas marked with the antibody, but stromal and vascular endothelial cells in the tissues surrounding these lesions also marked focally. Marking of vascular endothelium in a variety of benign tissues, renal tubular epithelium, and occasionally uterine smooth muscle cells was also observed. Normal breast tissue from 4 patients without breast cancer did not react. Studies on breast tumors revealed that 15/20 invasive ductal, 3/4 in situ ductal, 3/3 medullary, 2/2 invasive lobular, and 1/1 colloid carcinomas marked with this antibody. Image analysis revealed that the staining intensity of medullary carcinoma was twice that found in invasive ductal carcinoma (avg pixel density 76.6 vs. 30.1; P < 0.05). Invasive lobular and in situ ductal carcinoma also expressed higher staining intensities than invasive ductal carcinoma, but these differences were not significant. Invasive ductal carcinomas had heterogeneity in staining intensity (avg. pixel intensity range: 0 94 units). Tumors with multiple aneuploid populations had significantly higher stain intensity values than either diploid lesions or lesions containing a single aneuploid population (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505700 TI - Proteinase K inactivation of cytosolic aspartate aminotransferase isoenzyme for measurement of human serum mitochondrial aspartate aminotransferase. AB - We studied a new proteinase K assay method for human serum mitochondrial aspartate aminotransferase. We found that proteinase K showed no inactivation of human mitochondrial aspartate aminotransferase isoenzyme and complete inactivation of cytosolic aspartate aminotransferase. Previous studies have shown that selective proteolytic measurement for mitochondrial aspartate aminotransferase in serum using the protease 401 cleaved peptide bond at Leu 20 from the amino-terminal bond shows complete inactivation of cytosolic aspartate aminotransferase and slight inactivation of mitochondrial aspartate aminotransferase isoenzyme, depending on protease concentration. In this investigation, we found that the proteinase K method does not depend on protease concentration. The proteinase K enzyme inactivation of cytosolic aspartate aminotransferase is caused by the cleavage of the peptide bond at Ileu 21 from the aminoterminal bond. In studies with various animal cytosolic aspartate aminotransferase isoenzymes, proteinase K almost completely inactivated cytosolic aspartate aminotransferase. Precision and correlation using proteinase K for measurement of serum mitochondrial aspartate aminotransferase in human showed a good coefficient of variation (within-run < 4.45%) and a coefficient of correlation of r = 0.985 (N = 125). PMID- 8505701 TI - Analysis of human sera for filarial IgM antibody using antigen fractions isolated from immune complexes. AB - Filarial IgM antibody response to various antigenic fractions isolated from immune complexes by SDS-PAGE viz., IC-2, IC-4, IC-7, and IC-9, was studied by ELISA. The IgM antibody response to almost all antigenic fractions was seen more in microfilaraemic group compared to the clinical filariasis group. The antibody response to IC-9 antigen fraction as compared to other fractions was found significantly higher in microfilaraemic patients than in patients with clinical manifestations. Ninety percent of microfilariae carriers and 75% of clinical filarial patients have shown IgM isotype to IC-9 antigen. Studies with various lectins have revealed the Con A binding nature of IC-9 antigen. This study suggests that IC-9 antigen could be another candidate antigen in the immunodiagnosis of lymphatic filariasis. PMID- 8505702 TI - Stability studies of the components of a prototype penicillinase (beta-lactamase) linked ELISA kit. AB - Penicillinase (beta-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37 degrees C and 2-8 degrees C). Stability studies were conducted on previously validated assay for pregnanediol-3 alpha-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37 degrees C for 1 week and at 2-8 degrees C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37 degrees C up to 1 week and at room temperature up to 2 weeks and at 2-8 degrees C for a period of 6 months, during which the stability was studied. PMID- 8505703 TI - Effects of social comparison direction, threat, and self-esteem on affect, self evaluation, and expected success. AB - Two studies explored the conditions under which social comparisons are used to manage negative affect and naturalistic threats. Study 1 examined induced mood and dispositional self-esteem as determinants of affective responses to upward and downward comparisons. Consistent with a mood repair prediction, only low-self esteem Ss in whom a negative mood had been induced reported improved mood after exposure to downward comparison information. Study 2 examined the impact of naturalistic threats on responses to comparison information. Relative to a no comparison baseline, low-self-esteem Ss who had experienced a recent academic setback reported more favorable self-evaluations and greater expectations of future success in college after exposure to downward comparison information. These results remained significant after controlling statistically for general distress. Implications for downward comparison theory are discussed. PMID- 8505704 TI - Affect, cognition, and awareness: affective priming with optimal and suboptimal stimulus exposures. AB - The affective primacy hypothesis (R. B. Zajonc, 1980) asserts that positive and negative affective reactions can be evoked with minimal stimulus input and virtually no cognitive processing. The present work tested this hypothesis by comparing the effects of affective and cognitive priming under extremely brief (suboptimal) and longer (optimal) exposure durations. At suboptimal exposures only affective primes produced significant shifts in Ss' judgments of novel stimuli. These results suggest that when affect is elicited outside of conscious awareness, it is diffuse and nonspecific, and its origin and address are not accessible. Having minimal cognitive participation, such gross and nonspecific affective reactions can therefore be diffused or displaced onto unrelated stimuli. At optimal exposures this pattern of results was reversed such that only cognitive primes produced significant shifts in judgments. Together, these results support the affective primacy hypothesis. PMID- 8505705 TI - Beyond simple pessimism: effects of sadness and anger on social perception. AB - In keeping with cognitive appraisal models of emotion, it was hypothesized that sadness and anger would exert different influences on causal judgments. Two experiments provided initial support for this hypothesis. Sad Ss perceived situationally caused events as more likely (Experiment 1) and situational forces more responsible for an ambiguous event (Experiment 2) than angry Ss, who, in contrast, perceived events caused by humans as more likely and other people as more responsible. Experiments 3, 4, and 5 showed that the experience of these emotions, rather than their cognitive constituents, mediates these effects. The nonemotional exposure to situational or human agency information did not influence causal judgments (Experiment 3), whereas the induction of sadness and anger without explicit agency information did (Experiments 4 and 5). Discussion is focused on the influence of emotion on social judgment. PMID- 8505706 TI - Variability in the likelihood of automatic attitude activation: data reanalysis and commentary on Bargh, Chaiken, Govender, and Pratto (1992) AB - This commentary addresses J. A. Bargh, S. Chaiken, R. Govender, and F. Pratto's (1992) conclusion that automatic attitude activation depends not on the idiosyncratic strength of the association in memory between an attitude object and an individual's evaluation of the object but on normative considerations constant across individuals. A variety of difficulties with the bases for this conclusion are discussed. Moreover, additional analyses of the J.A. Bargh et al. data reveal the superiority of an idiosyncratic measure of associative strength (a given individual's latency of response to an attitudinal inquiry) in predicting automatic attitude activation over the various normative measures (latency, extremity, ambivalence, polarization, and consensus or consistency) that were examined. These results support the theoretical premise that attitude activation varies as a function of position along an idiosyncratically defined attitude-nonattitude continuum. PMID- 8505707 TI - Models of crossed categorization and intergroup relations. AB - Two studies explored 6 models of crossed categorization. In Experiment 1, Muslims (majority) and Hindus (minority) in Bangladesh evaluated 1 of 4 target groups created by crossing religion (Hindu or Muslim) and nationality (Bangladeshi or Indian) and then rated the target group's perceived variability. Experiment 2 was an extension of the research, including new measures. Both studies showed additive effects of religion and nationality, as predicted by 3 models, a strong effect of category dominance for religion, and out-group homogeneity only when the religious in-group was the dominant and majority group in its country. Experiment 2 also showed a significant relationship between discrimination based on religion and self-esteem and marginal support for the hierarchical ordering model. When and how specific models of crossed categorization might operate in different intergroup contexts are discussed. PMID- 8505708 TI - Gender and the relationship between job experiences and psychological distress: a study of dual-earner couples. AB - This article examines the association between job role quality and psychological distress in a sample of 300 full-time employed dual-earner couples, controlling for such individual level variables as age, education, occupational prestige, and marital quality and for such couple level variables as length of marriage, parental status, and household income. The magnitude of this effect is compared for men and for women. Results indicate that job role quality is significantly negatively associated with psychological distress for women as well as for men and that the magnitude of the effect depends little, if at all, on gender, casting doubt on the widely held view that job experiences more significantly influence men's mental health states than women's. The results are discussed in the context of differentiating between sex differences and gender differences. PMID- 8505709 TI - Implications of agency and communion for patient and spouse adjustment to a first coronary event. AB - The present study examined the effects of agency and communion on psychological adjustment to a 1st coronary event. Patients were interviewed about agency and communion and psychological adjustment in the hospital shortly before discharge (Time 1) and then reinterviewed along with spouses in their homes 3 months after discharge (Time 2). It was hypothesized that the extreme agentic orientation (unmitigated agency) and the extreme communal orientation (unmitigated communion) would be associated with poor adjustment for patients and spouses but that agency would promote self adjustment and communion would promote partner adjustment. In general, results confirmed predictions. It was suggested that the most distressed couples consist of a patient high in unmitigated agency and a spouse high in unmitigated communion. Although patients in such couples did not evidence the most distress, spouses did. PMID- 8505710 TI - Attachment styles, coping strategies, and posttraumatic psychological distress: the impact of the Gulf War in Israel. AB - This study examines the association between adult attachment style and the way people reacted to the Iraqi missile attack on Israel during the Gulf War. One hundred forty Israeli students were interviewed 2 weeks after the war and classified according to their attachment style (secure, avoidant, or ambivalent) and residence area (dangerous vs. less dangerous). Ambivalent people reported more distress than secure people. Avoidant persons reported higher levels of somatization, hostility, and trauma-related avoidance than secure persons. These results characterized Ss living in dangerous areas. In addition, secure people used relatively more support-seeking strategies in coping with the trauma, ambivalent people used more emotion-focused strategies, and avoidant people used more distancing strategies. Findings are discussed in terms of attachment working models. PMID- 8505711 TI - Day persons, night persons, and variability in hypnotic susceptibility. AB - Day persons (those most alert during daytime hours) and night persons participated in 2 experiments to examine within-subject variability of scores over time on the Harvard Group Scale of Hypnotic Susceptibility, Form A, and the Stanford Hypnotic Susceptibility Scale, Form C. Regardless of scale used, day persons exhibited peak susceptibility at 10 a.m. and 2 p.m.; for night persons, peak susceptibility was found at 1 p.m. and between 6 p.m. and 9 p.m. Furthermore, 2 peaks of temperature increase (1 p.m. and 6 p.m.) appeared to be associated with peaks in hypnotic susceptibility. However, such was shown to be associated with periods of food intake rather than with increases in hypnotic susceptibility. Results are examined with respect to methodological concerns and the potential existence of ultradian rhythms for hypnotic responsiveness. PMID- 8505712 TI - The divided self: concurrent and longitudinal effects of psychological adjustment and social roles on self-concept differentiation. AB - The relation between self-concept differentiation (SCD), the tendency to see oneself as having different personality characteristics in different social roles, and psychological adjustment was examined in a sample of college students and a sample of middle-aged women. In both studies, Ss with high levels of SCD showed poor emotional adjustment (e.g., depression) and tended to reject social norms and conventions (e.g., low socialization). Longitudinal analyses demonstrated that these same characteristics measured at age 21 predicted SCD measured more than 30 years later in middle age. These findings provide strong evidence that SCD is a sign of fragmentation of the self rather than specialization of role identities. The social context was also an important determinant of SCD; both dissatisfaction with role performance and frequent role changes in relationships and jobs predicted SCD measured 9 years later. PMID- 8505713 TI - Stability of emotion experiences and their relations to traits of personality. AB - The article presents a theoretical framework for studying emotion-personality relations and an empirical study of the stability of 88 normal middle-class mothers' emotion experiences and their relations to personality during the 3 years after childbirth. Ss completed the Differential Emotions Scale (DES), Eysenck's Personality Questionnaire, Jackson's Personality Research Form, and Zuckerman's Sensation Seeking Scale. The DES demonstrated stability over 3 years. There was individual stability despite changes in group means during the postpartum period. Positive emotionality, as well as the discrete emotions of interest, enjoyment, and shyness, predicted Extraversion. Negative emotionality and the discrete negative emotions were significant predictors of Neuroticism. Positive emotionality was inversely related to Neuroticism. There were expectable correlations among specific emotions and primary traits of personality. PMID- 8505714 TI - "Judgable" people: personality, behavior, and competing explanations. AB - "Judgability" discriminates people who are open and knowable from those who are closed and enigmatic. The current study investigated this individual difference characteristic and its personality and behavioral correlates. Subjects (N = 164) were videotaped interacting with a partner of the opposite sex. They completed several personality measures, and each subject was described by 2 friends. Three indices--subject-peer agreement, peer-peer agreement, and peer-behavior agreement -formed a reliable composite index of judgability. The correlates of judgability included extraversion, agreeableness, conscientiousness, emotional stability, and, more generally, psychological adjustment. PMID- 8505715 TI - [Measurement of vertebral bone density. Quantitative tomodensitometry or dual photon absorptiometry?]. AB - We have compared vertebral bone density measurements (QCT and DXA) in women in the postmenopausal period who underwent both examinations. Our aim was to study the results and to define the respective indications of QCT and DXA in various clinical pictures of osteoporosis. The subjects of the study were distributed into various groups according to the presence or absence of vertebral collapse and/or peripheral fractures. The results of the measurements were expressed as Z scores (deviation from age-normal average) to suppress the age effect and to make comparison between both methods possible. The values of both measurements are significantly lower in case of vertebral involvement. QCT is more sensitive than DXA to discriminate vertebral collapse. A vertebral fragility threshold was defined at a Z-score of -1 with DXA and -1.25 with QCT, corresponding to the best sensitivity for an acceptable specificity. The results of densitometry suggest that there is a peripheral osteoporosis, different from vertebral osteoporosis, as early as the postmenopausal period. Since DXA is easy to implement, it can be used to screen osteoporosis. When the vertebral measurement with DXA is normal although osteoporosis is obvious (previous collapse or fracture), QCT must be used as it is more sensitive. PMID- 8505716 TI - [X-ray computed tomography in the surgical approach management of impacted mandibular premolars]. AB - One case of ectopic mandibular dental impaction is presented. A decision to operate, for by chronic headache, was made. Only computed tomography showed the appropriate surgical approach, which was exobuccal in this case. PMID- 8505717 TI - [Ultrasound-guided biopsy in focal lesions of the liver. Report on an automated biopsy system]. AB - Two techniques for focal liver lesion biopsy were retrospectively evaluated to compare relative safety and efficacy. After sonographic localization of the focal liver lesion and biopsy with a hand-held 18-gauge cutting needle, a pathologically adequate specimen was obtained in 49 of 55 cases (89%) requiring 1 to 4 passes (mean, 2.1 per patient). A major complication occurred in one case and minor complication were noted in three cases. Forty one biopsies were performed by using a single use automatic core biopsy system with a 18-gauge cutting needle and real time sonographic guidance. With this automatized technique, specimens adequate for diagnosis were obtained in 40 of 41 cases (97.5%), requiring only 1 pass in all cases. Neither major nor minor complication was noted with this technique. We conclude that using sonographic guidance, the automatic core biopsy system with a 18-gauge cutting needle yields a slightly better rate of adequate specimens with a lower frequency of complications. PMID- 8505718 TI - [High-resolution x-ray computed tomography in the study of the pulmonary parenchyma. Personal experience]. AB - High-resolution CT (HRCT) scans were performed on 156 patients, using a bone reconstruction algorithm, 1.5 mm sections at 4 cm intervals from apex to base of the lungs and a 512 x 512 matrix. The patients either appeared to have a pathologic condition on chest film, or they presented positive clinical symptoms- i.e., cough, dyspnea, fever--and questionable/negative chest films. Since HRCT is capable of showing the secondary lobule, we employed it to study both its anatomy and the alterations that can modify its normal morphology--i.e., thickening of interlobular septa, reticular pattern, nodular pattern, high-density areas, sub pleural lines, honeycomb pattern. HRCT findings in secondary lobules, airways, and pleura were examined. They were: lymphangitic spread of carcinoma, pulmonary fibrosis, sarcoidosis, pneumoconiosis, interstitial edema, inflammatory disorders, bronchiectasis, emphysema, and bullae. Even though some limitations still exist due to the non-specificity of HRCT findings, the latter is the best method currently available to recognize and locate interstitial conditions and, sometimes, to make a diagnosis--e.g., of lymphangitic spread of carcinoma, interstitial edema, fibrosis, emphysema, bronchiectasis. Moreover, HRCT can accurately locate pathologic areas for lung biopsy and can be used instead of chest radiographs in the follow-up. PMID- 8505719 TI - [Superinfection of ovarian dermoid cyst. Apropos of a case]. AB - One case of a rare complication of dermoid ovarian cyst is reported: infection. Sonographic examination was not helpful, mainly due to a great quantity of gas within the mass. However radiography of the abdomen with the patient upright and CT showed a gas-fluid level, teeth and presence of fat. These findings permitted diagnosis of a complicated ovarian dermoid cyst before surgery. PMID- 8505720 TI - [Industrial news]. PMID- 8505721 TI - [Is there still a role for a non-English orthopedic literature?]. PMID- 8505722 TI - [Medical education in Australia]. PMID- 8505723 TI - Public health medicine--a different kind of ethics? PMID- 8505724 TI - Education attainment, nutrition and home conditions. PMID- 8505725 TI - The ascent of Cinderella. PMID- 8505726 TI - A study of the referral patterns and therapeutic experiences of 100 women attending a specialist premenstrual syndrome clinic. PMID- 8505727 TI - Paraneoplastic syndromes in patients with ovarian neoplasia. AB - The prevalence of several paraneoplastic syndromes associated with ovarian cancer was determined from a clinicopathological study of 908 patients with primary ovarian malignancy in the North East Thames Region. The diversity and rarity of these manifestations are great and the explanation for them is difficult. Circumstantial evidence suggests that in some cases an autoimmune phenomenon is the most plausible cause. PMID- 8505729 TI - Audit and accountability: the missing dimension? PMID- 8505728 TI - Hartmann's procedure: an appraisal. AB - Ninety-seven patients underwent Hartmann's procedure between 1981 and 1986 at the University Hospital, Nottingham. Sixty-one (63%) required this operation as an emergency procedure. There was an overall mortality of 22% and the morbidity rate was 56%. Infective and cardiovascular problems accounted for 77% of all complications encountered reflecting the age and underlying condition of the patients requiring this procedure. Thirty patients had successful restoration of intestinal continuity, the majority of these having their original procedure performed as an emergency for benign disease. There were no immediate postoperative deaths from reanastomosis and few short- or long-term anastomotic problems, however there was again considerable postoperative morbidity. PMID- 8505730 TI - The genetic mosaic. AB - Blaschko's lines are the acknowledged markers which represent the patterns of systematized naevi. Their interpretation has remained mysterious, because certain special features which they exhibit are impossible to reconcile with any known anatomical system in the human body. It is proposed that by changing one's views on the nature and growth of the dermatome, the patterns of zoster, and the behaviour of tissue mosaicism, the major difficulties hitherto experienced will be overcome. PMID- 8505731 TI - Heat shock protein and the double insult theory for the development of insulin dependent diabetes. AB - Heat shock proteins (HSP) are the most widely conserved group of proteins in phylogeny and play an important role in infection and autoimmunity. HSP65 has been suggested as the primary antigen in insulin dependent diabetes while an alternative antigen glutamic acid decarboxylase (GAD), has similar amino acid sequences. A 'double insult theory' for the development of insulin dependent diabetes is suggested whereby a bacterial infection leads to the production of HSP antibody. If during a 'window of opportunity' this is followed by a viral infection of the islet cells this could, in certain histocompatibility locus antigen (HLA) groups only, lead to the production of HSPs on the cell surface and a destructive autoimmune reaction. PMID- 8505732 TI - Uses and limitations of monoclonal antibodies (MoAbs) in the treatment of malignant disease: a review. PMID- 8505733 TI - Czarist police, roses, seashore, performing apes and phagocytosis. PMID- 8505734 TI - Untreated congenital adrenal hyperplasia presenting with severe androgenic alopecia. PMID- 8505735 TI - Cutaneous large cell anaplastic lymphoma. PMID- 8505736 TI - Kasabach-Merritt syndrome exacerbated by platelet transfusion. AB - Kasabach-Merritt syndrome is a complication of complex haemangiomas. We present a case in which standard treatment including platelet transfusion appeared to prolong and exacerbate subcutaneous bleeding. PMID- 8505737 TI - Orbital Kimura's disease. PMID- 8505738 TI - Sugar and coronary heart disease, a molecular explanation. PMID- 8505739 TI - Ventricular volume in schizophrenia. PMID- 8505740 TI - Generic prescribing of antidepressants. PMID- 8505741 TI - Avoiding bronchial trauma with double lumen tubes. PMID- 8505742 TI - Unexplained migraine. PMID- 8505743 TI - Health promotion or confusion? PMID- 8505744 TI - Neurological complications of acute childhood leukaemia. PMID- 8505745 TI - Mood change and perceptions of vitality: a comparison of the effects of relaxation, visualization and yoga. AB - The effects of three different procedures, relaxation, visualization and yogic breathing and stretch (pranayama) on perceptions of physical and mental energy and on positive and negative mood states have been assessed in a group of normal volunteers (N = 71, age range 21-76). Pranayama produced a significantly greater increase in perceptions of mental and physical energy and feelings of alertness and enthusiasm than the other two procedures (P < 0.5). Relaxation made subjects significantly more sleepy and sluggish immediately after the session than pranayama (P < 0.05). Visualization made them more sluggish but less content than pranayama (P < 0.05) and more upset than relaxation after the second session (P < 0.05). Thus, a 30 min programme of yogic stretch and breathing exercises which is simple to learn and which can be practised even by the elderly had a markedly 'invigorating' effect on perceptions of both mental and physical energy and increased high positive mood. A more extensive investigation is planned to establish whether such a programme can readily be incorporated into everyday life, and with what long-term results. PMID- 8505746 TI - Serum alpha interferon in children with right iliac fossa pain. AB - Serum alpha-interferon levels were analysed in 50 consecutive children admitted with right iliac fossa pain. Serum alpha-interferon levels were significantly raised in 33% of children without acute appendicitis when compared to 5.7% of children with histologically proven acute appendicitis and 9% of normal controls. This interesting phenomenon needs further investigation. A larger series may show it to be of clinical use in non-specific abdominal pain in childhood. PMID- 8505748 TI - Incidence of major complications of neurolytic coeliac plexus block. AB - The number of neurolytic coeliac plexus blocks carried out in England and Wales over a 5 year period (1986-1990) was ascertained. The number of cases of the major complications of permanent paraplegia and/or loss of anal and bladder sphincter function following on from such blocks, over the same period of time, was also ascertained. The information was obtained by means of a questionnaire which was sent to most of the pain clinics in England and Wales. There were 2730 neurolytic blocks carried out over the 5 year period. The number of cases of permanent paraplegia following on from the blocks was four. Of these four cases, three of them also had loss of anal and bladder sphincter function--loss of sphincter function never occurred in isolation. The incidence of major complications following neurolytic coeliac plexus block was thus one case per 683 blocks. PMID- 8505747 TI - The effectiveness of low dose slow release aspirin as an antiplatelet agent. AB - An open, randomized, parallel group study of three different aspirin preparations was carried out. The objective of this study was to compare their ability to inhibit the production of thromboxane A2 (measured as thromboxane B2 [TXB2]) from platelets. Three aspirin preparations were studied: Acetard 300 mg, Acetard 100 mg and Platet 100 mg. The study was conducted in 45 healthy adult volunteers and treatment continued once daily for 7 days. The results of the TXB2 assay show that the administration of all three treatment preparations produced a rapid drop in TXB2 levels of all volunteers. The baseline TXB2 level was reduced by 95% for all groups by day 3. Analysis by day showed a significant difference (P < 0.05) between treatments at day 1, with Acetard 100 mg having higher TXB2 levels than the other two groups. Analysis of changes from baseline showed a significant reduction (P < 0.05) in TXB2 levels at Days 1 to 14 for all three groups. Platelet aggregation also showed a significant reduction, being reduced to 10% of control at 7 days. It then reverted back to baseline by 28 days for all treatment groups. In conclusion, low dose aspirin is very effective as an antiplatelet agent and in a slow release form loses none of its patency. PMID- 8505749 TI - British gastroenterologists' care profile for patients with inflammatory bowel disease: the need for a patients' charter. AB - The follow-up of patients with inflammatory bowel disease (IBD) was investigated using a postal questionnaire sent to 359 members of the British Society of Gastroenterology (BSG), of whom 235 replied. Of patients with IBD, 96% were weighed on each out-patient clinic review and over 60% had their full blood count checked. Although few centres (20%) have computerized recall of their patients for cancer surveillance, 96% did perform such surveillance on patients with ulcerative colitis. The mean duration of disease before surveillance was initiated was 9.6 years. Most clinicians (80%) only surveyed patients with disease extending beyond the transverse colon. Despite recent work on cancer risk age is relatively unimportant to 76% of clinicians in their decision to screen or not. Only 24% of clinicians undertake cancer surveillance in patients with Crohn's disease but these use similar criteria in their selection of patients. Few other tests were performed regularly. Clinic services vary considerably from centre to centre, 62% offer open access to patients with IBD, 8% have a stoma nurse in clinic and 17% a dietitian. Eighty-four per cent of respondents provide educational books and 22% videos. Forty-four per cent of clinicians refer patients for advice to fellow sufferers. We believe there should be a uniform minimum standard of care and services available in clinics throughout the United Kingdom and propose a patients' charter to ensure that this occurs. Such care profiles provide guidelines to those who need to develop standards for resource management. PMID- 8505750 TI - What is going to happen to back pain? Discussion paper. PMID- 8505751 TI - Application of a general health policy model in the American health care crisis. AB - There is near consensus that the US health care system requires reform. Only a quarter of the American public has faith in the current system. Health care was one of the major issues considered in the 1992 US presidential election and the search for innovative solutions has transcended administrations. PMID- 8505752 TI - Two hundred years of drug abuse. PMID- 8505753 TI - A history of the use of arsenicals in man. PMID- 8505754 TI - Acute renal failure according to ancient Greek and Byzantine medical writers. PMID- 8505755 TI - Conn's syndrome due to a renin-responsive adrenal adenoma. PMID- 8505756 TI - Paraneoplastic eosinophilia in malignant melanoma. PMID- 8505757 TI - Atlantoaxial instability in monozygotic twins with Down's syndrome. PMID- 8505758 TI - Graves' disease: associated ocular myasthenia gravis and a thymic cyst. PMID- 8505759 TI - Cervical osteomyelitis and magnetic resonance imaging. PMID- 8505760 TI - Cardiac pre-excitation and haematemesis in oesophageal achalasia. PMID- 8505761 TI - Tracheostomy. PMID- 8505763 TI - He/she. PMID- 8505762 TI - Cyanocobalamin--a case for withdrawal. PMID- 8505764 TI - Nitrous oxide at homeopathic doses. PMID- 8505765 TI - Post anoxic action myoclonus. PMID- 8505766 TI - Are reminder stickers effective in reducing immunization dropout rates in Addis Ababa, Ethiopia? AB - A field trial to assess the effectiveness of a reminder sticker in reducing immunization dropout rates was conducted in two districts of Addis Ababa between 14 October 1991 and 31 January 1992. A total of 703 children were entered into the study. The study population was randomly divided into intervention and control groups. The intervention group received a reminder sticker and the control group did not. All other services were identical. A baseline interview documented the socio-demographic and maternal characteristics potentially related to immunization services utilization and revealed no statistically significant differences between the two groups. The dropout rates were 7.3 and 13.3% in the intervention and control groups respectively. This difference is clinically and statistically (P < 0.01) significant. Therefore, it is concluded that the reminder sticker is effective in reducing immunization dropout rates. Further investigations under operational conditions are recommended prior to the routine introduction of stickers into the immunization services. PMID- 8505767 TI - Malaria with bacteraemia in acutely febrile preschool children without localizing signs: coincidence or association/complication? AB - Data were collected on 642 preschool children who presented consecutively to casualty with fever and no localizing signs. Four hundred and forty-six (69%) had malaria parasitaemia. The proportion of children with bacteraemia was similar in those children with malaria (43/446, 9.6%) and those without malaria (24/196, 12.2%, P < 0.5). The pathogens in both groups of children were mainly Staphylococcus aureus and coliform bacteria. Although children with malaria/bacteraemia had a significantly higher prevalence of anaemia (P = 0.001), hepatosplenomegaly (P < 0.01) and combination of hepatosplenomegaly and severe anaemia (P = 0.02), compared with children with malaria alone, there was no correlation between the severity of parasitaemia and prevalence of malaria with bacteraemia. The association of malaria with bacteraemia appears to be coincidental. PMID- 8505768 TI - Studies on serum beta-glucuronidase activity and urinary tryptophan metabolites in human fascioliasis. AB - In the last few years, human fascioliasis has been reported more frequently from different parts of the world including Egypt. The present work aimed to study the ability of fascioliasis affected patients to metabolize tryptophan and to explore how this disease can affect the activity of the hydrolytic lysosomal enzyme beta glucuronidase. Liver and kidney functions and complete blood pictures of the studied patients were considered. Eleven tryptophan metabolites together with 4 pyridoxic acid, the major metabolite of vitamin B6, were determined. Fascioliasis showed an abnormal pattern of tryptophan metabolism which resembled that described earlier by Kupke and Knapp and which indicated that those patients were suffering from vitamin B6 deficiency. This conclusion was proved by the decreased levels of 4-pyridoxic acid. Abnormally high levels of beta-glucuronidase were also encountered in the fascioliasis cases which points to the liver damage caused by the fluke. PMID- 8505769 TI - Causes of morbidity among a sample of elderly hospital patients in Riyadh, Saudi Arabia. AB - The causes of admission to hospital over a 5-year period of 3539 persons aged 60 years and above in Riyadh, Saudi Arabia have been analysed; 54.2% were males and 45.8% females and 68.5% were aged 65 years and above. The causes of morbidity were chronic degenerative disorders of which cardiovascular diseases were the most frequent followed by acute respiratory problems, diabetes, and digestive and neoplastic diseases. The pattern of disease was very similar to that in the industrialized countries. The median stay in hospital was 10.7 days. Respiratory diseases and diabetes mellitus were significantly higher in females than males (P < 0.02), while cardiovascular diseases, particularly ischaemic heart disease and heart failure, as well as malignant neoplastic diseases mainly of the digestive system, were more prevalent in males. PMID- 8505770 TI - Prevalence of toxoplasmosis in humans and domestic animals in Ahwaz, capital of Khoozestan Province, south-west Iran. AB - From 1984 to 1988 sera from 1806 apparently healthy persons and 1096 patients suspected of toxoplasmosis in and around Ahwaz city, capital of Khoozestan province, Iran were examined by immunofluorescent antibody test (IFA). Prevalence of Toxoplasma antibodies at a titre of < or = 1:20 was found in 49.6% of healthy persons compared to 72.3% in suspected patients. The seropositivity rate was lowest in the new-born and children under 6 months of age and highest in persons 14-19 years old. Blood samples from 142 cattle, 138 sheep and 130 goats, collected from Ahwaz abattoir, were tested by the latex-agglutination test (LAT). The infection rates were 14.8, 13.8 and 13.1% respectively. The consumption of uncooked meat seems to be the most probable cause of the high infection rate of toxoplasmosis in the area. PMID- 8505771 TI - A rare complication of measles: subcutaneous and mediastinal emphysema. PMID- 8505772 TI - Reactive serological tests for syphilis in tropical spastic paraparesis: a dilemma. AB - The prevalence of reactive serological tests for syphilis (STS) was investigated in 183 Jamaican patients with tropical spastic paraparesis (TSP) and 200 age and sex matched controls. A significantly higher prevalence of reactive STS was found in TSP patients (34.9%) compared with controls (14.0%, P < 0.001). The biological false positive (BFP) rate was also significantly higher in TSP patients (P < 0.01) as well as controls (P < 0.001) over 40 years of age. However, these findings do not imply a pathogenetic role for treponemal disease in TSP. The high prevalence of reactive STS in Jamaican TSP patients may be multifactorial, and include biological false positives (BFP), previous childhood yaws and concurrent syphilis. PMID- 8505773 TI - The contribution of Gambian traditional birth attendants to field research. AB - One thousand, one hundred and forty-seven pregnant women from a rural area of The Gambia were followed throughout pregnancy. In order to determine the incidence of malaria infection of the placenta, traditional birth attendants (TBAs) from 18 villages were trained to collect placental biopsies and to prepare thick smears of placental blood at delivery. Nine hundred and eighty-eight of 1112 term deliveries (89%) occurred at home. Eight hundred and fifty-nine (87%) of these home deliveries were assisted by a TBA. TBAs collected 829 placental biopsies and 800 thick blood smears from the 859 women whom they assisted. Seven hundred and forty-seven thick blood films (93%) and 807 placental samples (97%) were satisfactory. TBAs are an important resource for clinical research; in this case they made a major contribution to a community study of the impact of malaria on pregnancy. PMID- 8505774 TI - Egg viability in urinary schistosomiasis. III. Repeatability and reproducibility of new methods. AB - Two new field methods for the detection and quantification of egg viability/hatchability in urinary schistosomiasis due to Schistosoma haematobium have been described recently, and compared with reference methods; the new methods are cheap and simple to use, and may be used singly or together. Before recommending their widespread use in control programmes, repeatability (r) and reproducibility (R) were studied using the guide for determination prepared by the British Standards Institution. Both parameters were found to be low in relation to the mean proportions of eggs viable/hatchable except at very low egg counts, and the new methods can safely be used in PHC-based control programmes. PMID- 8505775 TI - A national survey of the prevalence of chloroquine resistant Plasmodium falciparum in Burkina Faso. AB - Plasmodium falciparum susceptibility to chloroquine was investigated in 10 areas of Burkina Faso in the rainy seasons in 1990-1991. The 7-days in-vivo test was carried out from August to November on children aged 2-8 years with monospecific P. falciparum infection (asexual parasitaemia > 800 microliters-1 of blood), axillary temperature < 37.5 degrees C, and a negative Bergqvist urine test for 4 aminoquinolines. Among 2190 children screened, 366 were selected. Blood samples were collected on days 0, 2, 4 and 7 by finger-prick, and 100 microscopic fields of thick and thin smears were examined for parasite density and species identification. Chloroquine was given under supervision at the standard dose of 25 mg kg-1 over three days (days 0, 1 and 2) with an observation period of one hour after treatment. Parasitaemia did not clear in 63 cases (17.2%) with a 13.4% RII response and 3.8% RIII response. The results do not seem to indicate a decline in the sensitivity of P. falciparum to chloroquine in Burkina Faso during the past two years. PMID- 8505776 TI - Microbiology of cerebral abscess: a four-year study in Malaysia. AB - A prospective study was carried out to determine the aetiology of cerebral abscess in relation to the primary source of infections. Seventy-five patients with cerebral abscess were included in the study in the period January 1985 to December 1988. More than half of the patients studied had single lesions and the overall most common sites were in the frontal and parietal regions. Chronic suppurative otitis media, cyanotic congenital heart diseases and meningitis were among the important predisposing conditions in these patients. Approximately 25% of the patients with cerebral abscesses had no documented antecedent infections. Pure cultures were found to be predominant (66.7%) and sterile cultures were obtained from 10 (13.3%) patients. Streptococci were isolated from 23 (30.7%) patients, the commonest species being Streptococcus milleri. Proteus sp, Pseudomonas aeruginosa, Pseudomonas putrifaciens and Bacteroides sp were almost exclusively found in cerebral abscesses secondary to chronic suppurative otitis media; these organisms were found in mixed cultures. Streptococcus milleri, Bacteroides sp and Eikenella corrodens were found in pure cultures in patients with cyanotic congenital heart disease. In patients with ventriculoperitoneal shunts in-situ, Staphylococcus aureus, Staphylococcus epidermidis and diphtheroids were common. Anaerobes were found in 15 (20.0%) patients, the majority in mixed cultures. Culture, as well as gas-liquid chromatographic analysis of volatile fatty acids of cerebral pus, was carried out to enhance the detection of the anaerobes. Based on these findings, an antibiotic regimen consisting of penicillin, chloramphenicol and metronidazole is recommended as an initial therapy while awaiting culture and sensitivity results. PMID- 8505777 TI - Dengue fever complicated by pulmonary haemorrhage manifesting as haemoptysis. AB - A 17-year-old girl was admitted to hospital with dengue fever. On the ninth day of fever she developed haemoptysis and chest X-ray changes consistent with haemorrhage in her lungs. Thrombocytopaenia and mild coagulopathy were the most likely cause of this unusual haemoptysis in this patient. Investigations excluded other causes for the haemoptysis. PMID- 8505778 TI - Venous stasis complications of the use of the superficial femoral and popliteal veins for lower extremity bypass. AB - PURPOSE: The widely accepted durability of autogenous vein for infrainguinal arterial bypass has led the authors to use the superficial femoral and popliteal vein in selected cases. The results of this experience are presented. METHODS: From January through December 1991, during which 92 lower extremity bypass procedures were performed, deep vein bypass was attempted in seven patients (three femoral-popliteal grafts, two femoral-peroneal grafts, one femoral-deep femoral bypass, and one popliteal-posterior tibial bypass). In all cases the saphenous vein was absent or inadequate for use as a bypass conduit. The superficial femoral vein was harvested to below the knee in five patients. RESULTS: At last follow-up six of seven patients had patent grafts with relief of their original symptoms. All the procedures were complicated by venous stasis; acute postoperative phlegmasia developed in two cases. In one of these cases the limb was salvaged by below-knee fasciotomy and deep venous bypass (distal popliteal vein to common femoral vein with polytetrafluoroethylene). In the other case an above-knee amputation was required. Of the five remaining patients three had moderate venous stasis edema unresponsive to limb elevation and compression stockings after operation, and two have had resolution of minimal postoperative venous stasis with simple limb elevation. All cases of severe and moderate venous stasis occurred in patients with popliteal vein harvest to below the knee. CONCLUSIONS: The authors conclude that the use of the deep veins of the lower extremity for bypass is effective but is associated with a significant increase incidence of venous stasis edema. Two instances of phlegmasia were associated with popliteal vein harvest below the knee, and the authors caution against harvest of the popliteal vein to this level. PMID- 8505779 TI - Control of smooth muscle cell proliferation by psoralen photochemotherapy. AB - PURPOSE: Restenosis after balloon angioplasty or the intimal hyperplasia occurring at distal anastomoses of bypass grafts severely limits the long-term therapy for peripheral vascular disease. The aim of this study was to evaluate the application of psoralen photochemotherapy with ultraviolet A (UVA)-activated 8-methoxypsoralen (8-MOP) to suppress smooth muscle cell (SMC) proliferation in vitro by the formation of 8-MOP-DNA monoadducts and interstrand cross-links to inhibit DNA synthesis. METHODS: Bovine aorta SMC (2 x 10(4)/cm2) were treated with 8-MOP (0 to 1000 ng/ml) for 30 minutes, followed by UVA (2 joule/cm2) to determine the dose of 8-MOP and UVA that inhibits SMC proliferation. RESULTS: The results show that 8-MOP in the range 30 to 1000 ng/ml in combination with 2 joule/cm2 UVA inhibited SMC proliferation by 40% to 60% 3 days after treatment. In time course studies the growth of SMC treated with 100 ng/ml 8-MOP and 2 joule/cm2 UVA were monitored over 5 days, and this regimen was found to be cytostatic. SMC viability was confirmed by trypan blue exclusion. CONCLUSIONS: Our studies suggest that 8-MOP/UVA photochemotherapy may represent a novel approach to the control of localized SMC proliferation. PMID- 8505780 TI - Common carotid artery occlusion with patent internal and external carotid arteries: diagnosis and surgical management. AB - PURPOSE: Occlusion of the common carotid artery (CCA) is generally associated with occlusion of the ipsilateral internal carotid artery (ICA) and external carotid artery (ECA). Occasionally, however, collateral circulation to the ECA may preserve patency of the ICA via retrograde perfusion through the bulb. These patients may suffer ongoing transient ischemic attacks and risk for stroke. Recognition of this pathologic variant may allow for effective surgical intervention. METHODS: We have performed seven operations in six patients with occluded CCAs and patent ECA and ICAs. The occluded CCA was on the left side in each case (p < 0.01). Six of the operations were performed for ischemic symptoms, including amaurosis fugax in five patients, hemispheric TIA in one patient, and profound global ischemia in two patients who had concomitant occlusions of other extracranial vessels. In the five most recent cases the patent ECA and ICA above the occluded CCA were recognized by preoperative duplex scanning, which prompted cerebral angiography. A variety of reconstructive procedures were used, depending on the pathologic anatomy. These procedures included subclavian or axillary artery to carotid artery bypass with carotid endarterectomy (five), carotid endarterectomy with thrombectomy of the proximal CCA (one), and ascending aorta to carotid artery bypass (one). RESULTS: There were no strokes associated with the surgery, although one patient had transient neurologic symptoms and a seizure associated with documented reperfusion edema. Three of the patients had preoperative and postoperative transcranial Doppler studies that documented significant improvement in intracranial hemodynamics. Five of the patients have had continuously patent grafts with relief of symptoms for an average of 40 months (range 3 to 155 months). The remaining patient had graft occlusion after 72 months and underwent repeat operation for amaurosis fugax and global ischemia. His second graft remains patent, and he is symptom free 21 months later. CONCLUSIONS: Recognition of patent distal vessels above a CCA occlusion depends on a high index of suspicion, careful investigation of the carotid bulb with duplex scanning, and delayed arteriographic views of the bulb allowing for late collateral vessel filling. The favorable results in this small series of patients supports an aggressive surgical approach when patients with symptoms are encountered with patent distal vessels above an occluded CCA. PMID- 8505781 TI - Pedal bypass versus tibial bypass with autogenous vein: a comparison of outcome and hemodynamic results. AB - PURPOSE: Autogenous vein grafts to infrapopliteal arteries performed for chronic limb-threatening ischemia between 1984 and 1991 were reviewed to determine whether bypasses to pedal arteries produce results comparable to those obtained after supramalleolar tibial or peroneal bypasses. METHODS: Pedal bypass (dorsal pedal, n = 41; below-ankle posterior tibial, n = 12) was performed only if a suitable tibial target artery was not available. These grafts were compared with tibial (including peroneal) bypass grafts (n = 203). All grafts were placed for rest pain (23%) or established tissue loss (77%). RESULTS: Patients requiring pedal bypass were more likely to have diabetes and congestive heart failure but less likely to have a history of smoking. Age, gender, previous myocardial infarction, and other comorbidities were similar in the two groups. Operative mortality rates (30 days) were higher for pedal than tibial bypasses (9% vs 2%; p = 0.021), possibly reflecting the higher prevalence of diabetes, congestive heart failure, and more advanced systemic atherosclerosis associated with severe tibial artery disease. Most grafts were in situ saphenous vein (70% pedal vs 79% tibial). Life-table 3-year primary graft patency (58% pedal vs 61% tibial), secondary patency (82% pedal vs 79% tibial), limb salvage (92% pedal vs 87% tibial), and patient survival (61% pedal vs 64% tibial) were comparable in the two groups. Improved assisted primary patency and secondary patency rates in both groups were primarily a result of revision of graft-threatening lesions detected with noninvasive graft surveillance before thrombosis. Mean postoperative ankle/brachial index was similar for pedal and tibial bypasses, whereas mean duplex-estimated graft flow was less for pedal grafts (88 +/- 10 ml/min vs 129 +/ 6 ml/min; p = 0.002). Pedal bypass represented 21% of our experience with infrapopliteal vein grafts for chronic limb-threatening ischemia and was required more frequently in diabetic patients. Operative mortality rates were higher in patients undergoing pedal bypass, suggesting that aggressive preoperative diagnostic studies and perioperative monitoring may be appropriate for this group. Long-term survival was similar. CONCLUSION: We conclude that autogenous vein pedal bypass grafts provide hemodynamic results and limb salvage rates comparable to more proximal tibial bypasses in properly selected patients. PMID- 8505782 TI - A modified, angioscopically assisted technique for in situ saphenous vein bypass: impact on patency, complications, and length of stay. AB - PURPOSE: The impact of preoperative saphenous vein mapping and intraoperative angioscopy on the results of in situ saphenous vein bypass is analyzed in this study. METHODS: A new technique developed for in situ saphenous vein bypass (ISVB) was used in 26 patients (group I) and consisted of (1) preoperative duplex scanning and mapping of the saphenous vein and its tributaries, (2) small incisions for dissecting the proximal and distal arteries and veins, (3) ligation of marked tributaries through small incisions, (4) angioscopically directed incision of venous valves with a flexible-tipped valvulotome, and (5) femoral and distal anastomoses. The results were compared with those of 14 patients (group II) in whom the technique was similar except that venous tributaries were identified angioscopically and then ligated and 24 patients (group III) who underwent standard "open" ISVB through one long incision without angioscopy or vein mapping and in whom valvulotomy was carried out with a rigid valvulotome passed through tributaries. RESULTS: In comparing the results of groups I and III, significant reductions in operative intravenous fluid requirements (1930 ml vs 2675 ml; p = 0.04), postoperative length of stay (4.4 days vs 9.1 days; p < 0.001), and wound complications (1 vs 9; p = 0.01) were observed. Angioscopic irrigation fluid volume in group I was less than that in group II (360 ml vs 1014 ml; p < 0.001). At 12 months, the primary graft patency rate in all 64 patients was 91% for femoropopliteal and 89% for femoral-infrapopliteal ISBV and 84% for the 40 patients in groups I and II. CONCLUSIONS: This report demonstrates the effectiveness of our modified technique for ISVB, which helped reduce wound complications and length of stay while satisfactory early graft patency was also maintained. PMID- 8505783 TI - The potential for lower extremity revascularization without contrast arteriography: experience with magnetic resonance angiography. AB - PURPOSE: We report an initial experience with 24 patients studied between March 1990 and April 1992 with magnetic resonance angiography (MRA) for lower extremity occlusive disease. METHODS: All patients underwent vascular intervention with either balloon angioplasty or bypass grafting, and in six patients this intervention was based on MRA findings alone. Eighteen patients were studied with both MRA and contrast arteriography, and there was observed agreement between the two studies in 98% of all arterial segments examined. RESULTS: Agreement between MRA and contrast arteriography was uniform for arterial segments below the inguinal ligament. Intraoperative findings and favorable early results of seven bypass grafts performed in six patients after MRA alone suggested this was a valid approach for patients at prohibitive risk of complications from contrast arteriography. CONCLUSIONS: Magnetic resonance angiography is accurate in demonstrating relevant anatomy in peripheral arterial occlusive disease and in selected patients may eliminate the need for contrast arteriography before lower extremity revascularization. PMID- 8505784 TI - The effect of endothelial cell coculture on smooth muscle cell proliferation. AB - PURPOSE: Smooth muscle cell (SMC) growth kinetics are often studied in culture without consideration of endothelial cell (EC) influences that occur in vivo. This study examined the time-dependent effect of EC on SMC in a new type of coculture system. METHODS: Bovine aortic EC and SMC were harvested from fresh specimens, grown to four passages from primary cultures, and plated on either side of a porous 13 microns thick polyethylene terephthalate membrane. SMC were studied in coculture opposite from confluent EC (EC/SMC). Controls included SMC cultured opposite SMC (SMC/SMC) or SMC alone (with no cells on the opposite side of the membrane, phi/SMC). After cocultures were established, SMC were harvested from 1 to 4 days after release from growth arrest (n = 5 cultures/day/group). SMC DNA and protein content and 3H-thymidine incorporation were measured in each group. SMC proliferation was indexed by 3H-thymidine incorporation per cellular DNA content. RESULTS: EC stimulated SMC proliferation 56% more than SMC/SMC cultures and 244% more than SMC alone on day 1 after growth arrest (p < 0.05). This effect decreased with time so that by day 4, EC seemed to inhibit SMC proliferation (49% less proliferation than SMC/SMC and 76% less than SMC alone, p < 0.05). SMC opposite EC had significantly less protein/DNA than control SMC, and they retained a thin, spindle shape compared with the hypertrophic appearance of SMC in the absence of EC. Electron microscopy revealed EC gap junctions and cytoplasmic projections from SMC of sufficient length to transverse the pores in the coculture membrane. CONCLUSIONS: This coculture method has several useful features, including an appropriate luminal/abluminal EC/SMC orientation, a short distance between the cell layers, the potential for cell-to-cell contact, and the ability to separate the cell types for assays. It is clear that EC markedly affect SMC proliferation, protein/DNA ratio, and structure in coculture with dynamic interactions occurring for at least 4 days. These effects must be considered when attempting to model in vivo phenomena in tissue culture. PMID- 8505785 TI - Angioscopic evaluation of unilateral aortic graft limb thrombectomy: is it helpful? AB - PURPOSE: Graft thrombectomy is often an effective method for restoring inflow in an occluded limb of an aortobifemoral graft. A major determinant for its success is the completeness of thrombus removal from the graft, verification of which can be performed by angioscopy. METHODS: A retrospective review since January 1989 identified 51 unilateral graft limb thrombectomy operations in 35 patients. At the discretion of the surgeon 20 of these procedures included angioscopic inspection of the graft for significant retained thrombus, which was found and retrieved in 11 (55%). RESULTS: Visualization of the graft limb was very good, but inspection of the graft body was not possible. There were no angioscopy related complications. Within the first 4 months after graft limb thrombectomy and reconstruction, four of 20 patients in the group inspected by angioscopy and nine of 31 in the conventionally treated group had reocclusion of the treated limb. CONCLUSIONS: These results suggest that angioscopy can be a helpful adjunct in the successful inflow management of aortic graft limb thrombectomy to verify the completeness of clot removal. PMID- 8505786 TI - Do infected inguinal lymph nodes increase the incidence of postoperative groin wound infection? AB - PURPOSE: Risk factors for postoperative wound infection in patients undergoing vascular surgery may include age, comorbid conditions, wound classification, use of prosthetic grafts, and repeat operations. Groin incisions, in particular, pose substantial risk during placement of prosthetic grafts. METHODS: To investigate the role of infected inguinal lymph nodes (LN) in groin wound infection (GWI), we excised an inguinal LN from 69 consecutive patients (89 groins) undergoing 36 infrainguinal reconstructions, 24 aortobifemoral bypasses, 12 extra-anatomic femoral bypasses, 11 vein stripping, and 6 femoral pseudoaneurysm repairs. LN Gram staining was performed, and aerobic and anaerobic cultures were obtained. In addition cultures were taken from any ulcerated or gangrenous lesion on the ipsilateral open extremity lesion. RESULTS: Bacteria were isolated from 10 of 89 LN (11.2%) and included Staphylococcus species, gram-negative rods, diphtheroids, and Peptostreptococcus. Three of the 10 LN were taken from extremities with open lesions; seven were not. In no case did organisms cultured from a groin LN correlate with its corresponding open extremity lesion. Four GWI developed after operation (4%). In each case results of the groin LN cultures were negative. Three of the GWI were associated with an ulcerated or gangrenous lesion on the ipsilateral extremity (p = 0.08, odds ratio = 7.6), but in only one case did the organisms from the GWI correspond to that in the open lesion. The development of a GWI was strongly associated with insulin-dependent diabetes mellitus (p = 0.009, odds ratio = 22.9). CONCLUSION: In conclusion, 11% of groin LN harbored bacteria, but none of these were associated with subsequent development of a wound infection. Instead, insulin-dependent diabetes mellitus and the presence of an open skin lesion on the ipsilateral extremity seemed to be associated with an increased risk of wound infection. PMID- 8505787 TI - The neurovascular outcome of scapulothoracic dissociation. AB - PURPOSE: The purpose of this study was to define the role of acute revascularization in the management of scapulothoracic dissociation (SD), a rare injury of the upper extremity in which severe traction to the shoulder girdle results in combined arterial, brachial plexus, and musculoskeletal injury. METHODS: The results of a retrospective study of 11 patients with SD who were compared with 41 patients from the literature are presented. RESULTS: All 11 patients were involved in high-speed accidents. All patients had chest wall hematoma, absent radial pulse, and complete brachial plexus palsy. All patients had subclavian or axillary occlusion shown by angiography; one patient with simultaneous brachial artery injury had limb-threatening ischemia. No patient had active bleeding from the injured artery. Six limbs were revascularized, five were not. All five non-revascularized limbs remained viable. No patient had delayed hemorrhage. No patient had significant neurologic recovery; all limbs remained insensate and functionless. Two viable arms underwent late amputation because of neurologic dysfunction. CONCLUSION: The infrequent occurrence of delayed hemorrhage and limb-threatening ischemia and the dismal functional outcome of the brachial plexus injury suggest a conservative policy toward revascularization for the arterial injury in SD. PMID- 8505788 TI - Vascular surgery: the burr under the saddle. AB - A decade ago vascular surgery "came of age" with formalization of accreditation of training programs and certification of subspecialists in the field. These events created turbulence in general surgery, with initial resistance to further subspecialization and fragmentation of the specialty. Subsequent reassessment of the trends in general surgery and its subspecialty disciplines has led to a reaffirmation of the integrity of the parent specialty. Recent proposals for reforms in resident training in general surgery and its subspecialties are currently being evaluated. Despite the current rapprochement between general and vascular surgery, many challenges remain for both disciplines. All surgeons, regardless of specialty, should broaden their respect for both "microscience," particularly molecular biology, and "macromedicine," including epidemiology, preventive medicine, and health services research. PMID- 8505789 TI - Endovascular surgery credentialing and training for vascular surgeons. PMID- 8505790 TI - Reporting standards for lower extremity arterial endovascular procedures. Society for Vascular Surgery/International Society for Cardiovascular Surgery. PMID- 8505791 TI - Spinal cord ischemia after abdominal aortic procedures: is previous colectomy a risk factor? AB - Pelvic ischemia is a potential cause of spinal cord infarction after abdominal aortic surgery. Although postoperative cord ischemia is often unpredictable, certain patient subgroups may be at greater risk and identified as such before surgery. The case of a 64-year-old man who became paraplegic after an infrarenal aortoiliac aneurysm repair is reported. He had lost his mesenteric arcade as a result of a prior colectomy. Aortoiliac reconstruction required the interruption of antegrade hypogastric blood flow. Restoring circulation to at least one hypogastric artery is a tenet of modern aortic surgery. However, the loss of both internal iliac arteries and the occlusion of the inferior mesenteric artery at its origin are occasionally well tolerated because of a mesenteric collateral pathway. Colectomy eliminates the mesenteric arcade and further increases the risk of spinal ischemia when attempts at pelvic revascularization have failed. PMID- 8505792 TI - A second look at the etiology of spinal cord damage in surgery of the abdominal aorta. PMID- 8505793 TI - Circumferential venolysis and paraclavicular thoracic outlet decompression for effort thrombosis of the subclavian vein. PMID- 8505794 TI - Pulmonary function after upper dorsal sympathectomy. PMID- 8505795 TI - Comment on "Magnetic resonance angiography of peripheral runoff vessels". PMID- 8505796 TI - Thoracic dorsal sympathectomy for hyperhidrosis: a new approach. PMID- 8505797 TI - Decay and revival of vascular surgery. PMID- 8505798 TI - Angioscopically directed interventions improve arm vein bypass grafts. AB - PURPOSE: Our purpose was to determine the incidence and segmental distribution of intraluminal disease in the arm veins of patients in whom saphenous vein was unavailable or inadequate for bypass, determine whether angioscopic evaluation and directed interventions can upgrade the quality of arm vein conduit and improve early graft patency, and describe the angioscopic technique of in situ retrograde arm vein inspection. METHODS: Retrospective review of 109 infrainguinal arm vein bypass grafts in 104 patients performed with intraoperative angioscopic vein preparation and monitoring between August 1989 and March 1992 was undertaken. Four additional arm veins harvested were discarded because of diffuse disease. RESULTS: Intraluminal disease was noted in 71 (62.8%) of 113 arm veins, "webs" in 61 (54%), vein sclerosis in 25 (22.1%), localized stenosis in 11 (9.7%), and thrombus in 7 (6.2%). Intraluminal disease was most common in the cephalic (forearm 49.2%; arm 35.1%) and median cubital (33.3%) veins and least common in the basilic vein (11.7%). Eighty-three angioscopically directed interventions in 68 of 71 abnormal arm veins resulted in upgraded vein conduit quality in 47 (66.1%) of 71. Primary patency (< 30 days) was 99 (90.8%) of the 109 grafts, 85 (95.5%) of 89 grafts with normal or upgraded quality conduits, and 14 (70%) of 20 inferior-quality grafts (p = 0.0024). These differences persisted through 1 year by life-table analysis, (p < 0.001). CONCLUSIONS: Not only is the routine use of the angioscope in arm vein bypass grafting a sensitive technique to detect the intraluminal diseases so prevalent in arm veins but it can also direct endoluminal and surgical interventions that upgrade the quality of the vein conduit and improve early graft patency. PMID- 8505799 TI - A piece of my mind. Code magic. PMID- 8505800 TI - 'Best data yet' say air pollution kills below levels currently considered safe. PMID- 8505801 TI - Will civilian physicians see post-Somalia malaria? PMID- 8505802 TI - Criteria for evaluating potential transplant recipients vary among centers, physicians. PMID- 8505803 TI - From the National Institutes of Health. PMID- 8505804 TI - From the Centers for Disease Control and Prevention. Commercial fishing fatalities--Alaska, 1991-1992. PMID- 8505805 TI - From the Centers for Disease Control and Prevention. Fatalities attributed to entering manure waste pits--Minnesota, 1992. PMID- 8505806 TI - Scientific misconduct. PMID- 8505807 TI - Scientific misconduct. PMID- 8505808 TI - CA-125 as a screening test for ovarian cancer. PMID- 8505809 TI - HMG CoA reductase inhibitors and quality of life. PMID- 8505810 TI - Eosinophilia-myalgia syndrome or fibromyalgia with eosinophilia? PMID- 8505811 TI - The use of blood cultures. PMID- 8505812 TI - The Mammography Quality Standards Act of 1992. PMID- 8505813 TI - Organ procurement expenditures and the role of financial incentives. AB - OBJECTIVES: To evaluate the billed charges for organ procurement and to consider the role of financial incentives to encourage organ donation. DESIGN: Observational study. Data were obtained on donor organ acquisition charges from a random sample of kidney, heart, liver, heart-lung, and pancreas transplants. SETTING: The data were based on 28.7% of all transplants performed in the United States in 1988. MAIN OUTCOME MEASURE: Total charges for donor organ acquisition. RESULTS: The median charges (1988 dollars) for donor organs were as follows: kidney, $12,290; heart, $12,578; liver, $16,281; heart-lung, $12,028; and pancreas, $15,400. Since 1983, kidney acquisition charges have increased by 12.9%, heart charges by 64.1%, and liver charges by 61.8%, after adjusting for inflation. Between 9% and 31% of total transplant procedure-specific charges were associated with donor organ acquisition. CONCLUSIONS: There is wide unexplained variation in organ procurement charges. Data on actual costs are required to establish the appropriateness of current charges. Prevailing billing and payment methods should be reevaluated in an effort to address a variety of issues related to reimbursement. Current payment methods may actually contribute to cost inefficiency. Finally, while financial incentives may enhance the efficiency of organ procurement efforts, they will adversely affect the cost-effectiveness of transplantation. PMID- 8505814 TI - Long-term outcome of critically ill elderly patients requiring intensive care. AB - OBJECTIVE: To evaluate the long-term mortality and morbidity of critically ill elderly patients requiring intensive care. DESIGN: Prospective comparison of outcome of critically ill patients aged 75 years and older with patients aged 65 to 74 years. PATIENTS: Critically ill patients aged 65 years and older who required intensive care and who were recruited during a 3-month period. MAIN OUTCOME MEASURES: Duration of hospitalization, hospital charges, procedures used in the intensive care unit, mortality in the hospital and during the follow-up period, and quality of life of survivors during the follow-up period. RESULTS: Ninety-seven patients were included in the study; 54 were 75 years or older and 43 were aged 65 to 74 years. No significant difference was noted between the two groups for length of stay in the hospital, hospital charges, or mortality at 1 year. Severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation score at the time of intensive care unit admission, was a better predictor of survival than age. Quality of life, as assessed by activities of daily living, perceived quality of life, and Center for Epidemiologic Studies Depression score, were not significantly different in either group at 1, 6, and 12 months after discharge from the hospital. Most patients in both groups described their quality of life as adequate and were willing to receive intensive care again, if necessary. CONCLUSION: Age alone is not an adequate predictor of long-term survival and quality of life in critically ill elderly patients. PMID- 8505815 TI - Use of MEDLINE by physicians for clinical problem solving. AB - OBJECTIVE: To understand the ways in which computer-mediated searching of the biomedical literature affects patient care and other professional activities. Undertaken to determine the ways in which on-line access to the biomedical literature via the National Library of Medicine's MEDLINE database "makes a difference" in what physicians do when confronted with a medical problem requiring new or additional information. DESIGN: An adaptation of the Critical Incident Technique used to gather detailed reports of MEDLINE search results that were especially helpful (or not helpful) in carrying out the individual's professional activities. The individual physician was the source of the patient care incident reports. One thousand one hundred fifty-eight reports were systematically analyzed from three different perspectives: (1) why the information was sought; (2) the effect of having (or not having) the needed information on professional decisions and actions; and (3) the outcome of the search. PARTICIPANTS AND SETTING: Telephone interviews were carried out with a purposive sample of 552 physicians, scientists, and other professionals working in a variety of clinical care and other settings. Of these, 65% were direct users of MEDLINE throughout the United States, and 35% had MEDLINE searches conducted for them either at a major health sciences center or in community hospitals. RESULTS: Three comprehensive and detailed inventories that describe the motivation for the searches, how search results affected the actions and decisions of the individual who initiated the search, and how they affected the outcome of the situation that motivated the search. CONCLUSIONS: MEDLINE searches are being carried out by and for physicians to meet a wide diversity of clinical information needs. Physicians report that in situations involving individual patients, rapid access to the biomedical literature via MEDLINE is at times critical to sound patient care and favorably influences patient outcomes. PMID- 8505816 TI - Changes in bone density with lactation. AB - OBJECTIVE: To test the a priori hypotheses that significant bone loss occurs in lactation of greater than 5 months' duration and that bone mass returns to baseline levels when breast-feeding ceases. DESIGN: Prospective cohort study design of 12 months' duration. SETTING: General community setting with recruitment occurring at birthing education classes. PARTICIPANTS: Volunteer sample of 98 healthy women of white (n = 95) and Asian (n = 3) origin, aged 20 to 40 years, and 0 to 1 parity prior to parturition, grouped according to lactation duration: 0 through 1, 2 through 5, and 6 or more months. MAIN OUTCOME MEASURES: Bone mineral density (BMD) of the proximal femur was measured by dual-energy x ray densitometry at 2 weeks (baseline), 2 months, 4 months, 6 months, and 12 months following parturition, and BMD of the lumbar spine was measured at baseline, 6 months, and 12 months after parturition. RESULTS: Women with lactation duration of 6 months or longer had mean BMD losses of 5.1% and 4.8% at the lumbar spine and femoral neck, respectively, comparing baseline values with those at 6 months post partum. Women who breast-fed 0 through 1 month lost no BMD at either bone site. Bone loss in women who breast-fed 6 months or longer was not explained by differences in age, diet, body size, or physical activity. Among women who breast-fed 6 months or longer, there was evidence of return to baseline levels of the lumbar spine at 12 months after parturition. The BMD of the lumbar spine of those women who continued to breast-feed more than 9 months had increased but was still significantly lower than baseline. CONCLUSION: Extended lactation (> or = 70% of energy intake is provided for > or = 6 months) is associated with bone loss; however, there is evidence of return to baseline BMD measurement at 12 months after parturition. PMID- 8505817 TI - Socioeconomic inequalities in health. No easy solution. AB - OBJECTIVE: Socioeconomic status (SES) is strongly associated with risk of disease and mortality. Universal health insurance is being debated as one remedy for such health inequalities. This article considers mechanisms through which SES affects health and argues that a broader and more comprehensive approach is needed. DATA SOURCES: Published articles surveyed using MEDLINE and review articles and bibliographies. METHODS AND RESULTS: Research is reviewed on the association of SES with health outcomes in different countries, including those with universal health coverage. Socioeconomic status relates to health at all levels of the SES hierarchy, and access to care accounts for little of this association. Other mechanisms are suggested and implications for policy and clinical practice are discussed. CONCLUSION: Health insurance coverage alone is not likely to reduce significantly SES differences in health. Attention should be paid both in policy decisions and in clinical practice to other SES-related factors that may influence patterns of health and disease. PMID- 8505818 TI - The accuracy of magnetic resonance imaging in patients with suspected multiple sclerosis. The Rochester-Toronto Magnetic Resonance Imaging Study Group. AB - OBJECTIVE: To design and implement a methodologically rigorous study to examine the accuracy of magnetic resonance imaging (MRI) in a patient population clinically suspected of having multiple sclerosis (MS). DESIGN AND SETTING: Three hundred three patients, who were referred to two university medical centers because of the suspicion of MS, underwent MRI of the head and double-dose, contrast-enhanced computed tomography (CT) of the head. The images were read by two observers individually and without knowledge of the clinical course or final diagnosis. Patients were followed up for at least 6 months and reevaluated clinically with subsequent neurological examination. Final diagnosis (MS or not MS) was made by a panel of neurologists on the basis of the clinical findings at presentation, those that developed during follow-up, and other diagnostic tests. The results of the imaging procedures were excluded to avoid incorporation bias. Diagnostic accuracy was assessed using receiver-operating characteristic analysis and likelihood ratios. RESULTS: Magnetic resonance imaging of the head was considerably more accurate than CT in diagnosing MS. The area under the receiver operating characteristic curve for MS was 0.82 (compared with 0.52 for CT) indicating that MRI was a good but not definitively accurate test for MS. A "definite MS" reading on an MRI of the head was specific for MS (likelihood ratio, 24.9) and essentially established the diagnosis, especially in patients clinically designated as "probable MS" before testing. However, MRI of the head was negative for MS in 25% and equivocal in 40% of the patients considered to have MS by the diagnostic review committee (sensitivity, 58%). CONCLUSIONS: Magnetic resonance imaging of the head provided assistance in the diagnosis of MS when lesions were visualized. Its ability far exceeded imaging with double contrast CT. The sensitivity and, therefore, the predictive value of a negative MRI result for MS were, however, not sufficiently high for a normal MRI to be used to conclusively exclude the diagnosis of MS. PMID- 8505819 TI - Hereditary hemochromatosis. PMID- 8505820 TI - Cardioversion during pregnancy. PMID- 8505821 TI - Exercise and blood donation. PMID- 8505822 TI - EEG findings in Creutzfeldt-Jakob disease. PMID- 8505823 TI - The cost of total parenteral nutrition: is the price right? PMID- 8505824 TI - Does perioperative total parenteral nutrition reduce medical care costs? AB - An economic analysis accompanied a multicenter Department of Veterans Affairs randomized, controlled trial of perioperative total parenteral nutrition (TPN). The cost of providing TPN for an average of 16.15 days before and after surgery was $2405, more than half of which ($1025) included costs of purchasing, preparing, and delivering the TPN solution itself; lipid solutions accounted for another $181, additional nursing care for $843, and miscellaneous costs for $356. Prolonged hospital stay added another $764 per patient to the $2405 cost of providing TPN, bringing the total to $3169. The incremental costs attributed to perioperative TPN were highest ($3921) for the patients least likely to benefit, that is, those who were less malnourished and at low risk of nutrition-related complications. Incremental costs were lowest ($3071) for high-risk patients. On the basis of the hospital-based method of administering TPN that was used in the clinical trial, perioperative TPN did not result in decreased costs for any subgroup of patients. PMID- 8505825 TI - Metabolic bone disease in adults receiving long-term parenteral nutrition: longitudinal study with regional densitometry and bone biopsy. AB - A syndrome of bone pain and fractures has been described in patients receiving long-term support from parenteral nutrition containing large quantities of aluminium or vitamin D2. Whether this same syndrome occurs in patients supported by current therapeutic regimens is controversial. In this study, bone health was longitudinally evaluated over 7 to 61 months in 14 subjects maintained on long term parenteral nutrition. The parameters of bone health evaluated included bone mass as measured by single and dual photon absorptiometry and quantitative histomorphometry of bone biopsies. There was a striking heterogeneity in baseline measures of bone health. Mean bone density of parenteral nutrition patients was significantly below expected values on entry into the study at both the distal radius (z score = -0.76 +/- 0.27) and the lumbar spine (z score = -1.17 +/- 0.27). Mean areal density at the forearm was less severely depressed (z score = 0.62 +/- 0.34). The longitudinal changes in bone density and morphology were heterogeneous, with some subjects showing deterioration, others improvement, and still others no change. We conclude that patients already established on parenteral nutrition frequently have osteopenia. The group as a whole did not demonstrate normalization of the osteopenia, but our results also suggest that current parenteral nutrition formulations low in aluminum and vitamin D2 do not necessarily cause worsening of bone health. The etiology of this clinical syndrome merits additional study. PMID- 8505826 TI - Early vs delayed vitamin A supplementation in very-low-birth-weight infants. AB - The purpose of this trial was to test the hypothesis that vitamin A adequacy may decrease the incidence of bronchopulmonary dysplasia (BPD) in very-low-birth weight infants. Serum vitamin A levels were measured and the effects of two regimens of vitamin A supplementation on the incidence of BPD were compared. There were 24 infants in each of two groups with a mean birth weight less than 1000 g, a mean gestational age of 27 weeks, and similar sexual and racial mixes. In group I, vitamin A levels were measured after 1 week of parenteral nutrition and, if low, the infant was given a 2000-IU supplement intramuscularly three times a week, beginning on the 10th to 14th day of life. In group II, the same supplementation was begun on the second to fourth day of life. In both groups, when enteral feedings reached 60 kcal/kg per day, 2500 IU/d vitamin A was given orally. The incidence of oxygen support at 28 days was similar in both groups, although in group II there was a trend toward less vigorous ventilatory support. chi 2 analysis showed that a significantly smaller proportion of infants in group II had BPD at 36 weeks' gestational age than in group I. Length of neonatal intensive care unit stay was significantly reduced from 81 to 60 days. We conclude that vitamin A supplementation should be administered early to small, premature infants who are at risk for BPD and that monitoring of plasma levels is essential. PMID- 8505827 TI - Addition of glucagon to lipid-free total parenteral nutrition reduces production of prostaglandin E2 by stimulated splenic macrophages. AB - Sepsis is a major complication of total parenteral nutrition (TPN). Impaired immunity has been suggested as being responsible for TPN-related sepsis, but it is unknown how the immune system is affected by TPN. We recently found that administration of lipid-free TPN resulted in an increase in prostaglandin E2 (PGE2) release by stimulated splenic macrophages. This observation suggested that TPN may impair immunity through the prominent immunosuppressive effects of PGE2. In the present study, we tested the hypothesis that addition of glucagon to TPN solution may protect against the immunosuppressive effect of TPN by modifying PGE2 secretion. Adult, male Sprague-Dawley rats (n = 18) underwent jugular vein cannulation: group 1 (n = 7) received intravenous saline and chow ad libitum; group 2 (n = 6) received TPN (80 mL/24 h); and group 3 (n = 5) received TPN (80 mL/24 h) plus glucagon (100 micrograms/24 h). After 10 days, spleens were removed and splenic macrophages were isolated and cultured for 24 h in plain M199 medium (nonstimulated) or in medium containing Escherichia coli lipopolysaccharide (5 micrograms/mL) (stimulated). PGE2 release was determined by enzyme-linked immunosorbent assay. There were no differences in PGE2 release between the groups of nonstimulated cells, but when stimulated with lipopolysaccharide, the macrophages from the TPN rats (group 2) released more PGE2 (81.68 +/- 25.99 ng/2.5 x 10(6) cells) than the control group (16.04 +/- 3.26 ng/2.5 x 10(6) cells). The release of PGE2 was normalized in the TPN animals treated with glucagon (15.71 +/- 3.33 ng/2.5 x 10(6) cells). This difference was significant, with p < .05 by Tukey's test after analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505828 TI - Alanyl glutamine-enriched total parenteral nutrition restores intestinal adaptation after either proximal or distal massive resection in rats. AB - This study was designed to determine whether alanyl glutamine-containing total parental nutrition (TPN) can restore the impaired adaptive process of the remaining intestine, observed with administration of conventional TPN, after massive small-bowel resection. Seventy-four male Sprague-Dawley rats weighing 250 g were randomly divided into seven groups. Group I rats (n = 10) were killed after overnight fasting. Group II animals (n = 32) underwent massive small bowel resection (85%) with preservation of the first 15 cm of jejunum. Group III animals (n = 32) were also submitted to massive small-bowel resection with preservation of 15 cm of terminal ileum. Three different TPN solutions were prepared. Solution A was a conventional formulation that did not contain glutamine. Solution B contained 1.88 times the amino acid concentration of solution A. Solution C was prepared by adding alanyl glutamine (2 g/100 mL) to solution A. Solutions B and C were isonitrogenous and isocaloric. Each solution was infused to groups II and III, which were subdivided into groups IIA (n = 10), IIB (n = 11), IIC (n = 11), IIIA (n = 10), IIIB (n = 11), and IIIC (n = 11). After 1 week of TPN (270 kcal/kg per day), the experimental animals were killed and the intestine was taken for examination. Final body weight did not differ significantly among the groups, and there was no difference in nitrogen balance among the animals that received solution B or C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505829 TI - Aspirating gastric residuals causes occlusion of small-bore feeding tubes. AB - A frequent mechanical problem encountered with small-bore feeding tubes is lumenal obstruction of the tube. A number of studies have described methods to prevent tube occlusion and restore patency once the tube becomes occluded. It has been observed that most intact protein formulas will clot when acidified to a pH of less than 5.0. This study evaluated the question of whether gastric feeding tubes occlude more frequently when they are used for checking gastric residuals by aspirating acidic gastric juices into the tube than when gastric residuals are not checked. Patients who were fed intragastrically via a small-bore feeding tube with intact protein formulas were divided into two groups. Gastric residuals were checked in group A patients every 4 hours, whereas no residuals were checked in group B patients. Fifteen patients in group A were followed for a total of 138 patient days and 13 patients in group B were followed for 154 patient days. Ten occlusive episodes occurred in the group A patients, whereas only one occlusive episode occurred in the group B patients. This difference was statistically significant (p = .0171). We concluded that small-bore feeding tubes occlude more frequently when used to aspirate gastric residuals. PMID- 8505830 TI - The effect of increasing levels of fish oil-containing structured triglycerides on protein metabolism in parenterally fed rats stressed by burn plus endotoxin. AB - This report investigates the effect of various levels of medium-chain/fish oil structured triglycerides on protein and energy metabolism in hypermetabolic rats. Male Sprague-Dawley rats (192 to 226 g) were continuously infused with isovolemic diets that provided 200 kcal/kg per day and 2 g of amino acid nitrogen per kilogram per day. The percentage of nonnitrogen calories as structured triglyceride was varied: no fat, 5%, 15%, or 30%. A 30% long-chain triglyceride diet was also provided as a control to compare the protein-sparing abilities of these two types of fat. Nitrogen excretion, plasma albumin, plasma triglycerides, and whole-body and liver and muscle protein kinetics were determined after 3 days of feeding. Whole-body protein breakdown, flux, and oxidation were similar in all groups. The 15% structured triglyceride diet maximized whole-body protein synthesis (p < .05). Liver fractional synthetic rate was significantly greater in animals receiving 5% of nonprotein calories as structured triglyceride (p < .05). Muscle fractional synthetic rate was unchanged. Plasma triglycerides were markedly elevated in the 30% structured triglyceride-fed rats. The 30% structured triglyceride diet maintained plasma albumin levels better than those diets containing no fat, 5% medium-chain triglyceride/fish oil structured triglyceride, or 30% long-chain triglycerides. Nitrogen excretion was lower in animals receiving 30% of nonnitrogen calories as a structured triglyceride than in those receiving 30% as long-chain triglycerides, but this difference did not reach statistical significance (p = .1). These data suggest that protein metabolism is optimized when structured triglyceride is provided at relatively low dietary fat intakes. PMID- 8505831 TI - The importance of a source of sufficient protein in postoperative hypocaloric partial parenteral nutrition support. AB - A comparison of postoperative metabolic and nutritional responses to different hypocaloric parenteral nutrition supports was performed in 42 patients with various gastric lesions. Sixteen patients (group A) received 3000 mL of a 5% glucose in water or glucose in saline infusion per day after surgery (approximately 10 kcal/kg per day). Another 14 patients (group B) received 2000 mL of 5% glucose in water or saline plus 1000 mL of 5% amino acid solution per day (approximately 10 kcal/kg per day and 1 g of protein per kilogram per day). The other 12 patients (group C) received 2000 mL of 5% glucose in water or saline plus 500 mL of 5% amino acid solution and 500 mL of 10% fat emulsion (approximately 20 kcal/kg per day and 0.5 g of protein per kilogram per day). After 7 days of study, all three groups were found to have a decrease in body weight, mid-arm circumference, triceps skin-fold, and serum albumin level, and the differences among them were not significant. Groups B and C had significantly less negative mean nitrogen balance than group A (-5.54 +/- 0.63 g/d and -6.07 +/ 0.49 g/d vs -9.20 +/- 0.68 g/d). Group B also had a significantly greater increase of transferrin (from 175.5 +/- 9.9 mg/dL to 185.4 +/- 9.3 mg/dL) than group A and a significantly greater increase in total lymphocyte count (from 956 +/- 113 cells/mm3 to 1196 +/- 176 cells/mm3) than groups A and C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505832 TI - Kinetics and thermogenesis of medium-chain monocarboxylic and dicarboxylic acids in man: sebacate and medium-chain triglycerides. AB - The effects on oxygen consumption and carbon dioxide production of a constant intravenous infusion of 0.15 g of disodium sebacate (Sb), the sodic salt of a medium-chain dicarboxylic acid with 10 carbon atoms, per kilogram of body weight per hour over 5 hours and a 50% mixture of medium- and long-chain triglycerides (MCT/LCT) were compared in 10 healthy men. Oxygen consumption and carbon dioxide production were measured by indirect calorimetry. Mean oxygen consumption was about 19% higher than the basal oxygen consumption at the end of MCT/LCT infusion but was only 5% higher than the basal oxygen consumption when Sb was infused. There was an eightfold increase in plasma beta-hydroxybutyrate and acetoacetate concentrations and a threefold increase in serum insulin levels during MCT/LCT infusion, but no significant change in ketone bodies and insulin from basal values was observed during and after Sb infusion. Pharmacokinetic parameters were also computed, showing an average apparent volume of distribution of 167 mL/kg of body weight for MCTs and 112 mL/kg of body weight for Sb. The t1/2 of MCTs was 50 minutes and that of Sb was 78 minutes. Urinary excretion of Sb and its beta oxidative by-product, suberic acid, globally accounted for 48% of the given amount of Sb. In spite of its urinary loss and slower tissue uptake compared with MCTs, Sb avoided ketone body formation or elevation in insulin levels and did not induce a significant increase in oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505833 TI - Comparison of weighted vs unweighted enteral feeding tubes for efficacy of transpyloric intubation. AB - Routine transpyloric placement of feeding tubes reduces aspiration in intensive care unit patients. Spontaneous passage eliminates the need for radiologic or endoscopic intervention. It is unclear whether the addition of a weight to the end of the tube or the use of the prokinetic agent metoclopramide in the conventional dose (10 mg) improves spontaneous transpyloric placement. In a randomized, prospective trial, 39 intensive care unit patients (age > 2 years) had a total of 50 nasoenteral tubes placed after intravenous metoclopramide (20 mg in adults, 0.2 mg/kg in children). The tubes were 8 French in diameter with either a weighted end or an unweighted bullet tip. Tip position was confirmed radiographically within 4 hours after blinded placement and at 1 and 2 days if spontaneous passage had not occurred. At 4 hours, 36% of the weighted tubes and 84% of the unweighted tubes (p < .002) had passed through the pylorus. At 1 day, 48% of the weighted tubes and 86% of the unweighted tubes (p < .007) had achieved transpyloric position. At 2 days, 56% and 92% of the weighted and unweighted tubes, respectively, had passed through the pylorus (p < .009, chi 2). The occurrence of transpyloric passage and the rapidity at which it occurred was significantly greater for the unweighted tube during all time periods. A poststudy trial was conducted to evaluate the effect of the normal dose of metoclopramide (10 mg in adults and 0.1 mg/kg in children) and the transpyloric passage of the unweighted feeding tube. Twenty-five patients received 10 mg of metoclopramide before the insertion of the unweighted tube.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505834 TI - Reduction of the plasma levels of tissue plasminogen activator after infusion of a lipid emulsion in humans. AB - A lipid emulsion of soybean oil, egg lecithin, and glycerol, widely used as a standard component of parenteral nutrition regimens, has been reported to induce changes in some hemostatic parameters known to be associated with increased thrombotic risk. We studied the effect of a single infusion of this lipid emulsion (500 mL of a 10% emulsion, give over 5 to 6 hours) on the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1 antigens in 12 patients with various diseases. Twelve matched patients, not treated with lipid, served as controls. In patients receiving the lipid emulsion, tissue plasminogen activator was markedly reduced at the end of the infusion (p < .001) and remained significantly lower than the basal levels 24 hours later (p < .05). By contrast, in control patients, the activator was slightly but significantly increased (p < .01) at the time interval corresponding to the postinfusion sample. Plasminogen activator inhibitor 1 was similar in control and treated patients at all intervals. The release of tissue plasminogen activator in response to 10 minutes of venous stasis, evaluated in six lipid-treated patients at the end of the infusion, was not different from that observed in six control patients. It is concluded that the lipid emulsion induces a marked decrease in the circulating levels of tissue plasminogen activator. PMID- 8505835 TI - Intestinal amino acid absorption during sepsis. AB - Sepsis has been shown to cause a decrease in mesenteric blood flow in association with ultrastructural changes in the small intestine and impaired immune, barrier, and metabolic functions of the gut. These impairments in the structure and function of the gastrointestinal tract may have a detrimental effect on the morbidity and mortality of sepsis. Two recent studies have shown that the ability of the small intestine to absorb amino acids is also impaired during sepsis, but the systemic and cellular mechanisms of this impairment are not known. Release of cytokines induced by systemic bacteria or endotoxin may lead to a reduction in the synthesis of transporter proteins by the enterocyte at a time when there is reduced availability of both luminal (because of anorexia) and circulating (because of reduced mesenteric blood flow) substrates. Future research needs to investigate the systemic and local mediation of the sepsis-induced reduction in intestinal amino acid absorption and the possibility of correcting the defect by the administration of enteral nutrients, hormones, or drugs. PMID- 8505836 TI - Symptomatic vitamin A and D deficiencies in an eight-year-old with autism. AB - An 8-year-old boy with autism developed a limp and periorbital swelling. He was found to have hypocalcemia and radiographic evidence of rickets. Ophthalmologic examination revealed xerophthalmia and corneal erosions. Serum vitamin A was undetectable and serum 25-hydroxyvitamin D was decreased. Dietary history revealed a markedly altered intake consisting of only french fried potatoes and water for several years. All biochemical and physical abnormalities reversed with appropriate supplementation. The nutritional content of french fries is reviewed. Feeding dysfunction is an integral part of autism and closer attention should be paid to potential nutritional deficiencies. PMID- 8505837 TI - Spontaneous separation and migration of a metal splice segment of a repaired Hickman catheter. AB - Repairs to the external silicone central venous catheter segment are done to correct mechanical defects caused by natural wear and tear or traumatic catheter injury. The ability to repair a damaged catheter obviates the need for surgical replacement. Complications specific to repaired Hickman catheters have not been reported. We report a case in which the metal piece separated from the replacement segment of a Hickman catheter. This metal piece lodged 1 cm from the catheter entrance to the anterior chest and caused incomplete catheter occlusion. PMID- 8505838 TI - Use of sodium hydroxide solution to clear partially occluded vascular access ports. AB - Gradual vascular access port or tunneled central venous catheter occlusion during total parenteral nutrition is a common complication of unknown etiology, usually unresponsive to treatment with urokinase, ethanol, or hydrochloric acid. After establishing safety with regard to catheter materials and efficacy in dissolving the occluding substance in vitro, we treated a total of 13 vascular access ports (10 patients) that had occluded gradually during "three-in-one" total parental nutrition by slow perfusion with 10 to 20 mL of 0.1 mmol/mL sodium hydroxide solution. We found a mean increase in flow (results are flow rates under gravity dependent vascular access port inlet pressure of 1.5 kPa) from 37 microL/s (95% upper confidence limit, 45 microL/s) to 75 microL/s (95% lower confidence limit, 64 microL/s; p < .001). For normal use, a flow of 50 microL/s is sufficient. There were no side effects. Five vascular access ports remained in excellent function during a follow-up period of 9 months. The others had reocclusions, but the partial reocclusions could be treated successfully. PMID- 8505839 TI - A controlled trial of scheduled replacement of central venous and pulmonary catheters. PMID- 8505840 TI - Alterations in oropharyngeal flora in patients with a nasogastric tube: a cohort study. PMID- 8505841 TI - Use of triple-lumen subclavian catheters for administration of total parenteral nutrition. PMID- 8505842 TI - Risk of pulmonary aspiration among patients receiving enteral nutrition support. PMID- 8505843 TI - Plasma glutamine levels in septic patients. PMID- 8505844 TI - Home parenteral nutrition--a 3-year analysis of clinical and laboratory monitoring. PMID- 8505845 TI - Myelodysplastic syndromes: a forum for debate and discussion. PMID- 8505846 TI - B-cell chronic lymphocytic leukaemia populations respond stochastically to combinations of growth signals in vitro. AB - The ability of B-CLL lymphocyte populations to respond to cytokine stimulation of mononuclear cultures was examined using 3-colour immunofluorescence and multiparameter flow cytometry. The simultaneous detection of the membrane antigens CD5 and CD19, with the proliferation antigen Ki-67, allowed examination of the cell-cycle entry of the B-CLL lymphocyte population. Upon stimulation with IFN-gamma, IFN-gamma+IL-2, TPA+IL-4, between 10 and 44% of B-CLL lymphocytes from 10 patients were stimulated to enter into cell-cycle. This B-CLL response was notably more homogenous than the non-clonal lymphocyte response. Except in the case of IFN-gamma alone, T-cell response did not correlate with B-CLL response, suggesting B-CLL lymphocytes respond directly to combinations of growth signals. Considering the B-CLL population as homogenous, B-CLL lymphocytes respond in a stochastic manner. PMID- 8505847 TI - Induction of CD8 antigen and suppressor activity by glucocorticoids in a CEM human leukemic cell clone. AB - The relationship between glucocorticoid effect and regulation of cell surface antigens was investigated in two models of leukemic cell lines, CEM C7 denoted (r+, ly+) and CEM C1 (r+, ly-). The reactivity of murine monoclonal antibodies, anti-CD4-FITC, anti-CD8-FITC, anti-CD2-FITC and anti-calla-FITC, were analyzed using flow cytometry. The suppressor function was determined using [3H]thymidine incorporation into phytohemagglutinin-activated peripheral blood lymphocytes. Dexamethasone treatment of a human leukemic cell clone CEM C7 caused an increase in a subset of cells expressing the surface antigen CD8, which is present on suppressor and cytotoxic T-lymphocytes. By comparison, there was no modification of the expression of CD4 antigen, which is expressed at high levels in these cells. After two days of treatment with 5 x 10(-8) M dexamethasone, CEM C7 cells showed a two-fold increase in suppressor activity compared to untreated cells. In contrast, there was no regulation by glucocorticoids of either the CD8 or CD4 antigens in the leukemic clone CEM C1. Furthermore, no modification of the suppressor function in CEM C1 cells by dexamethasone was observed. In the human leukemic cells studied here, the ability to induce CD8 antigen expression in a CD4+ cells correlates with the ability to induce cell lysis in a glucocorticoid receptor positive cell population. PMID- 8505848 TI - Pregnancy associated increase in differentiation-stimulating factor (D factor)/leukemia inhibitory factor (LIF)-binding substance(s) in mouse serum. AB - Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) is known to have multiple biological activities besides induction of differentiation of mouse myeloid leukemia M1 cells. Little is known about how its activities are regulated in vivo, but it has been suggested to play a regulatory role in the mechanisms involved in development of mice. In this study, we found that a single class of D-factor-binding substance is present in normal mouse serum and that it increases transiently in the late stage of pregnancy. It inhibits the induction of differentiation of mouse myeloid leukemic M1 cells by D-factor by blocking the binding of this factor to the cells. It is a heat-labile protein with an apparent molecular weight of 130,000-150,000. The binding of 125I-D-factor to the substance is specific since it was inhibited by excess unlabeled D-factor, but not by interleukin 6 or interferon gamma. The dissociation constant of the binding substance for mouse D-factor in normal mouse serum is 6.6-9.4 nM. In the late stage of pregnancy, the amount of the D-factor-binding substance in the serum apparently increases about 30-fold. These results suggest that the D-factor binding substance regulates the activity of D-factor during embryonic development of mice. PMID- 8505849 TI - Interaction between tumor necrosis factor-alpha and HSP 70 in human leukemia cells. AB - We confirm here by immunoblotting that a cell line resistant to clonal inhibition from tumor necrosis factor (K562) expresses high levels of HSP 70, whereas two sensitive cell lines (HL60 blast and EM3) express low levels. When sensitive cell lines are exposed to tumor necrosis factor, HSP 70 is not generally induced; when tumor necrosis factor is removed, however, HSP 70 is transiently induced. In five bone marrow samples from patients, generally low levels of HSP 70 were detected. PMID- 8505850 TI - Complete variable region deletion in a mu heavy chain disease protein (ROUL). Correlation with light chain secretion. AB - In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed under dissociating conditions, but they were linked by non-covalent bridges to a portion of the serum short mu chains. The patient's urine contained a kappa type Bence-Jones protein. Study of a messenger RNA and complementary DNA from blood cells showed the abnormal mu chain to lack the entire variable region, likely due to a direct splicing of the leader peptide exon onto the CH1 exon. The production of light chains, a rare event in heavy chain diseases, appears to correlate with the occurrence of a heavy chain deletion restricted to the variable domain, likely because the non-covalently linked light chains allow these unusual heavy chains to be secreted. PMID- 8505851 TI - Analysis of the p53 gene in patients with isochromosome 17q and Ph1-positive or negative myeloid leukemia. AB - Increased incidence of p53 gene aberrations or chromosome 17p monosomy resulting from an isochromosome 17q [i(17q)] has been observed with transition of chronic myelogenous leukemia (CML) to myeloid blast crisis (BC), and in some patients with poor risk acute myeloid leukemia (AML) progressing from myelodysplastic syndrome (MDS). These data suggested that disease progression may be linked to bi allelic inactivation of p53. Here, we report on p53 gene analyses of nine patients with CML-BC and AML who showed an i(17q) as characteristic cytogenetic anomaly. Using Southern blots, agarose gel electrophoresis and single-strand conformation polymorphism analyses of PCR products from genomic DNA and cDNA, spanning exons 4 through 9, we did not detect any structural abnormalities of the remaining p53 allele. These findings question the hypothesis that p53 gene alterations are the principal molecular event responsible for progression of CML chronic phase or MDS to i(17q)-positive CML-BC or AML, respectively. PMID- 8505852 TI - Induction of surface antigen recognized by new monoclonal antibody, YU311, on 1 beta-D-arabinofuranosylcytosine-resistant human leukemic cell line. AB - A new monoclonal antibody, YU311, against an antigen expressed on 1-beta-D arabinofuranosylcytosine(ara-C)-resistant human leukemic cell line with decreased deoxycytidine kinase activity was generated. YU311 reacted with ara-C-resistant human leukemic cell line (KY-Ra), but not with its parental cell line (KY-821) which was sensitive to ara-C. YU311 recognized the 92-kDa membrane protein. Furthermore, YU311 inhibited the growth of KY-Ra in suspension medium with and without ara-C. In immunocytochemistry, there was no difference in expression of usual differentiation antigens between KY-Ra and KY-821. These findings indicate that antigenic change could occur in ara-C-resistant human leukemic cells with stable expression of differentiation antigens and that the 92-kDa membrane protein may be one of the membrane proteins which regulate cell growth of KY-Ra. PMID- 8505853 TI - Comparisons among external resistive loading, drug-induced bronchospasm, and dense gas breathing in cats: roles of vagal and spinal afferents. AB - In anesthetized cats, breathing spontaneously, increase in lung resistance (RL) was induced by either external resistive loads (ERL) or internal loading produced by dense gas breathing (sulfur hexafluoride, SF6) or serotonin (5-HT)-induced bronchoconstriction. The 3 test agents were used in each animal. Arterial blood gases were maintained in the normal range. Ventilatory and cardiovascular responses were studied in 3 groups of animals: intact, vagotomized, or spinalized at C8 level, a condition that preserved diaphragmatic afferents. In intact or spinal animals, ERL as well as SF6 inhalation lengthened the inspiratory and/or the expiratory periods, whereas 5-HT injections elicited rapid shallow breathing. The changes in ventilatory timing with either type of load were not observed in vagotomized cats. In all animals, ERL breathing or 5-HT injections increased the moving-time average of diaphragmatic EMG measured at constant time (Edi 0.1 and 0.5 secs), but this was not observed during SF6 inhalation, a condition in which the magnitude of RL increase was less than in the 2 other situations. The changes in systemic arterial blood pressure and/or cardiac frequency were mostly associated with 5 HT-induced bronchoconstriction. They persisted in spinalized cats, but were not observed or reversed in vagotomized ones. These observations demonstrate that vagal afferents play a major role in the changes in ventilatory timing and cardiovascular function in response to both external or internal moderate resistive loading. The existence of Edi changes in the 3 groups of cats suggests also that diaphragmatic afferents, preserved in both situations, are involved in this response. PMID- 8505854 TI - Amiodarone causes decreased cell-mediated immune responses and inhibits the phospholipase C signaling pathway. AB - Amiodarone can cause pulmonary toxicity along with an increase in phospholipid in macrophages, lymphocytes, and other cell types. Phospholipid accumulates because amiodarone inhibits the lysosomal phospholipases A1 and A2. Since a wide array of cells are affected by amiodarone and because amiodarone might inhibit other phospholipases, we postulated that cellular functions might be affected. Therefore, the major focus of this study was to determine whether amiodarone inhibited cellular functions. We found that alveolar macrophages isolated from drug-fed rats were significantly less phagocytic, and that the rats had significantly depressed delayed-type hypersensitivity responses. Spleen cells isolated from the drug-fed rats also had severely depressed mitogen responses. Since the spleen cell proliferative response could be partially restored by stimulating the cells with ionomycin and phorbol myristate acetate, we postulated that amiodarone was inhibiting phospholipase C. To substantiate this hypothesis, we found that amiodarone could directly inhibit phospholipase C in vitro. We conclude that amiodarone affects both phagocytic responses and the development of cell-mediated immunity and that the lack of these normal responses could exacerbate amiodarone toxicity. One possible mechanism for decreased cellular functions may be the inhibition of phospholipase C. However, further studies are necessary to confirm this finding. PMID- 8505855 TI - Differences in expression of monocyte/macrophage surface antigens in peripheral blood and bronchoalveolar lavage cells in interstitial lung diseases. AB - The surface antigens of monocytic cells in bronchoalveolar lavage (BAL) fluid were analyzed in 10 patients with sarcoidosis, 8 patients with idiopathic pulmonary fibrosis (IPF), 9 patients with extrinsic allergic alveolitis (EAA), and 10 healthy volunteers, and compared with the surface antigens of peripheral blood monocytes (PBM) of the same individuals. The absolute numbers of alveolar macrophages (AM) were increased in all disease groups as were the numbers of small monocyte-like cells, indicating an increased influx of PBM into the alveoli, which was the most prominent in EAA patients. In all groups investigated, the percentages of PBM positive for the monoclonal antibodies (mAb) CD13, CD14, CD33, U26, and Max3 were higher than the percentages of BAL macrophages positive for these markers, while the Max24 marker was equally expressed. In all groups the percentages of AM positive for RFD9 and CD68 were higher than the percentages positive for PBM. The absolute numbers of CD13+ macrophages were increased in IPF and EAA patients, probably due to the increased influx of monocytic cells. The 3 mAb in the CD68 cluster (i.e., Ki-M6, Ki-M7, and Y2/131) demonstrated marked differences in expression on PBM as well as on AM. This is probably because CD68(Ki-M6) recognizes a different epitope than CD68(Ki M7) and CD68(Y2/131). The latter 2 become increasingly expressed by AM and this is paralleled by an increased CD68(KiM6) expression. The expression of CD68, which is associated with the generation of oxygen radicals during the respiratory burst and increased chemiluminescence, tended to be elevated on PBM and AM of IPF patients, although with a broad range. PMID- 8505856 TI - Dexamethasone increases airway epithelial cell neutral endopeptidase by enhancing transcription and new protein synthesis. AB - Neutral endopeptidase (NEP; also known as EC 3.4.24.11, CALLA) is a widely distributed membrane-bound enzyme that hydrolyzes many biologically important endogenous peptides. To evaluate the influence of glucocorticoids on airway epithelial cell NEP expression, we used the human airway epithelial cell line Calu-1. Cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were incubated with different concentrations of dexamethasone or vehicle alone in the presence or absence of actinomycin D or cycloheximide for planned times. NEP activity was assayed at the end of treatment employing reverse-phase, high-pressure liquid chromatography. In some experiments, changes in NEP-specific mRNAs in the presence or absence of dexamethasone and/or the inhibitors were also evaluated by Northern blot analysis. We found that dexamethasone increased Calu-1 NEP activity in a dose- and time-dependent manner. Northern blot analysis indicated that NEP-specific mRNAs were also increased by dexamethasone. Furthermore, neither actinomycin D nor cycloheximide inhibited the increases in NEP activity and NEP-specific mRNAs caused by dexamethasone stimulation. We speculate, therefore, that dexamethasone increases NEP expression of these airway epithelial cells by enhancing transcription and new protein synthesis. PMID- 8505857 TI - Increased interleukin 6 production by bronchoalveolar lavage cells in patients with active sarcoidosis. AB - Alveolitis of sarcoidosis is characterized by activated alveolar macrophages (AMs) and T cells. The mediators interleukin-1 (IL-1) and interleukin 6 (IL-6) released by AMs represent essential factors for the progression of the T cells in the cell cycle. The role of IL-1 in pulmonary sarcoidosis has previously been studied; however, the relevance of other mediators (i.e. IL-6) has not yet been evaluated. We measured the spontaneous and lipopolysaccharide (LPS)-induced release of IL-6 and tumor necrosis factor alpha (TNF alpha) by bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMNC) in 6 control subjects (group A) and in 15 patients with sarcoidosis, 10 with active (group B), 5 with inactive disease (group C). IL-6 as well as TNF alpha were spontaneously released by BAL cells of the active group in significantly greater amounts compared to both other groups; IL-6: A, 165.5 pg/ml/24 hr/10(6) cells (range, 0 604), B, 946 (0-2467), C, 16.6 (0-83); TNF alpha: A, 162 pg/ml/24 hr/10(6) cells (0-523), B, 803 (100-17352), C, 100 (0-379). In all groups autologous PBMNC proved to be quiescent, releasing only baseline levels of the cytokines tested. After stimulation with LPS all these cells released great quantities of IL-6 and TNF alpha. In active disease a positive correlation between IL-6 and TNF alpha release was observed (r = 0.77, p < 0.02). The present study documents that in active sarcoidosis the spontaneous release of IL-6 by BAL cells parallels the spontaneous release of TNF alpha. IL-6 is capable of initiating the proliferation and activation of T cells in the lung. PMID- 8505858 TI - Inhibition of human monocyte TNF production by adenosine receptor agonists. AB - Adenosine receptor agonists and agents enhancing pericellular concentrations of adenosine possess antiinflammatory properties. In the present study, we found that R-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamido adenosine (NECA), other agonists of adenosine receptors and dipyridamole, an adenosine uptake inhibitor, inhibited tumor necrosis factor (TNF) production by endotoxin stimulated human monocytes in a concentration-dependent manner with no inhibition of interleukin-6. The rank order of agonist potency is characteristic of neither A1 nor A2 receptors and suggests the involvement of another receptor subtype. The effect of R-PIA on TNF was in part abolished by the antagonist 8 sulfophenyltheophylline. In endotoxin-treated rats, R-PIA pretreatment (2.5 mg/kg) reduced serum TNF levels by 98%, with no modification of serum IL6 levels. TNF inhibition could be an important mechanism by which adenosine analogs exert their antiinflammatory action. PMID- 8505859 TI - The optimal dosage of (-)deprenyl for increasing superoxide dismutase activities in several brain regions decreases with age in male Fischer 344 rats. AB - We previously reported that the optimal dosage of (-)deprenyl to increase superoxide dismutase (SOD) activities in striatum in rats differs 10 fold between young male and female rats (1). Furthermore, in female rats the optimal dosage increased with age (1). In the present study in order to clarify how the optimal dosage of this effect changes with age in male rats, we examined the effects of four different dosages of deprenyl on SOD enzyme activities in striatum and several other tissues in old (28-29-month-old) male Fischer 344 (F-344) rats. Continuous s.c. infusion of deprenyl for 3 wks increased activities of SOD and catalase (CAT) in striatum, substantia nigra and cortical regions but not in hippocampus, cerebellum or the liver. The dose of 0.5 mg/kg/day was found to be most effective, while higher (1.0, 2.0 mg/kg/day) or lower (0.1 mg/kg/day) dosages were less effective. This value of 0.5 mg/kg/day was 4 fold lower than the dosage of 2.0 mg/kg/day which was most effective in increasing SOD and CAT activities in young (5-7 month old) male rats of the same strain (1,2). The decline of the optimal dosage with age found in male rats is best explained by a possible decline with age in the hepatic microsomal monooxygenase enzyme activities that are involved with the metabolism of deprenyl. In view of the large differences in the optimal dosages shown among different sexes and ages of rats, future studies regarding the unique effect of this drug in prolonging the life span of rats must be carefully investigated with the caution in mind that the optimal dosage for the life prolonging effect may well differ depending on sex, age and possibly strain and species of animal model used. PMID- 8505860 TI - Expression of class II HLA molecules by endothelial cells of human decidua. AB - Many authors have documented a high level of expression of class II HLA molecules by decidua. Although macrophages appear to be responsible for this, we show in this article that endothelial cells (EC) of the venules and capillaries of human decidua also strongly express class II molecules, whereas EC of chorionic villi do not. We discuss this finding in the context of the maternal-fetal immune interaction. PMID- 8505861 TI - Systemic administration of interleukin-1 stimulates norepinephrine release in the paraventricular nucleus. AB - The purpose of this study was to investigate the effects of circulating interleukin-1 beta (IL-1 beta) on the release of norepinephrine (NE) in the paraventricular nucleus (PVN). After intraperitoneal administration of IL-1 beta, NE was measured by high performance liquid chromatography in the perfusate collected from the PVN of conscious, freely moving rats by the technique of push pull perfusion. IL-1 beta produced an increase in NE release. Both the strength and duration of NE release were dose-dependent. It is concluded that circulating IL-1 beta activates the noradrenergic innervation to the PVN and that this is part of the mechanism by which it stimulates the release of the corticotropin releasing hormone (CRH) and produces its other neuroendocrine and central effects. PMID- 8505863 TI - Imaging of the human cardiovascular system using the rapid echo flow-rephased spin-echo technique. AB - Using a flow-rephased spin-echo technique with a short echo time of TE = 9.7 msec, "white blood" multislice and single slice first echo images of the human heart were acquired using standard 1.5 T whole-body imagers. The technique almost completely eliminates phase shifts for flow with constant velocity and constant acceleration, so the investigations with healthy volunteers show images which are almost free of the artifacts often found in ECG-gated standard spin-echo imaging of the heart. T1-weighted images with good contrast between tissue and blood are achieved at any time during the whole heart cycle. The results obtained indicate that the technique might be helpful for imaging small vessels, vessels which contain slowly flowing blood, and vessels located in regions with static field inhomogeneities, for example, lung vessels. PMID- 8505862 TI - Effects of specific fatty acids on prolactin-induced NB2 lymphoma cell proliferation. AB - Nb2 rat lymphoma cells are dependent on prolactin (PRL) for growth. Membrane lipid composition of Nb2 cells undergoes rapid modification when these cells are grown in culture media supplemented with specific fatty acids. Since the actions of PRL are mediated through specific membrane receptors, the following studies were conducted to characterize the lipid-dependent events involved in fatty acid modulation of PRL-induced cell proliferation. Nb2 cells were grown in suspension cultures in control or fatty acid-supplemented media, in the presence of various doses of PRL. PRL-induced cell growth was significantly enhanced by arachidonate, but significantly attenuated by stearate supplementation of the culture media. A direct relationship was observed between the concentration of specific fatty acid added to the culture media and the magnitude with which this fatty acid was incorporated into Nb2 cell membranes, as determined by gas chromatography. Acute treatment with phorbol ester enhanced Nb2 cell growth in control media and reversed the attenuating effects of membrane stearic acid enrichment. However, PRL-induced Nb2 cell growth was similar with or without the presence of phorbol ester, when cells were grown in media supplemented with arachidonate. Addition of protein kinase C (PKC) inhibitors to control and fatty acid-supplemented media resulted in a dose-dependent inhibition of PRL-induced Nb2 cell proliferation. These results suggest that lipid modulation of Nb2 mitogenic-responsiveness to PRL is mediated through alterations in PKC activation. PMID- 8505864 TI - An evaluation of the significance of areas of intense signal in the MR brain images of patients with multiple sclerosis. AB - This study evaluates the distribution of areas of intense signal (AIS) in 189 patients with multiple sclerosis (MS) and 83 patients presenting high-risk factors of cerebrovascular injuries. Two multivariate statistical analyses (multifactorial discriminant analysis and logistic regression analysis) with two AIS scores and several subpopulations of patients (according to age and/or the number of AIS) were tested. The results of these analyses were expressed with the usual screening test. The results obtained in this study even without the help of any clinical information are very promising, since they established that the specificity of MRI could be improved by using the distribution of the AIS in the various anatomical areas as a criterion. Five regions of the brain display were particularly significant in the discrimination between MS and non-MS patients: In decreasing order we found that the temporal, occipital, brain stem, and parietal regions were more specific with respect to the diagnosis of MS, while only the basal ganglia could account for non-MS patients. With multifactorial discriminant analysis and logistic regression analysis respectively, 78.9 (+/- 2.8)% and 85.1 (+/- 2.8)% of the patients were correctly classified by MRI. The results obtained on the main group were confirmed by a predictive test carried out on an other population of 40 patients, which produced similar results. The comparison between our method and Fazekas's imaging criteria showed a 20% improvement in favour of our approach and it is hoped that it will contribute to make the most of MRI as a tool for the diagnosis of MS. PMID- 8505865 TI - Preliminary evaluation: magnetic resonance of urography using a saturation inversion projection spin-echo sequence. AB - A saturation inversion projection (SIP) spin-echo technique is reported which allows a reliable direct visualization of the urogenital system as well as its functional performance in magnetic resonance imaging. We used an imaging sequence with a 90 degree saturation pulse and two 180 degree inversion pulses followed by a short spin-echo (SE) pulse sequence. The three time intervals in the 90 degree 180 degree-180 degree-SE pulse train were adjusted to suppress the signals of soft tissues and fat. After intravenous injection of the contrast agent Gd-DTPA, a shortening of the kidney T1 and the T1 of the urogenital system is obtained below the T1 values of fat and soft tissues, and these remaining ultra-short T1 tissues were imaged with the SIP sequence. Using a sequential measuring technique a quantitative evaluation of the glomerular filtration rate seems to be possible with a time resolution of 18 sec per image. In addition, magnetic resonance urography using the SIP sequence provided a good visualization of the urogenital system and may show several clinical utilities in further clinical studies. PMID- 8505866 TI - Measurement of left ventricular mass in hypertrophic cardiomyopathy using MRI: comparison with echocardiography. AB - Left ventricular mass (LVM) is an important consideration in the management of cardiac hypertrophy associated with hypertrophic cardiomyopathy (HCM), systemic hypertension, and other diseases. A brief MRI cardiac imaging procedure used to monitor regression of LVM during treatment would be beneficial in management of these patients, since echocardiograms cannot be obtained in all patients and since the volume of a hypertrophic heart can straightforwardly be assessed from a series of tomographic slices. The present study was designed to evaluate a brief cardiac MRI procedure for measurement of LVM in HCM and compare it to echocardiography. MRI images acquired in a simulated transverse body plane were used to evaluate the mass of the left ventricle in 6 ex vivo human hearts obtained at autopsy. The estimates of LVM by MRI in the ex-vivo hearts were within 8% of the actual LVM. MRI images were acquired to evaluate LVM in 5 normal subjects and 12 patients diagnosed with HCM. Echocardiography was accomplished on 4 of the normal subjects and 10 of the patients having HCM. There were no significant differences in LVM by MRI and echocardiographic techniques in normal subjects. Transverse MRI images acquired on normal subjects demonstrated that estimates of LVM are reproducible when repeated over 3-w to 3-mo intervals. Images selected for analysis represented the heart in an early diastolic phase. MRI and echocardiographic techniques demonstrated significant differences in LVM in HCM patients. Estimates of LVM in normal subjects and patients diagnosed with HCM were normalized for body weight. The LVM estimates for HCM patients were very significantly different than normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505867 TI - Arterial edge artifacts in gated, phase re-ordered phase contrast angiography of the extremities. AB - Cardiac gating and phase re-ordered acquisition are often employed to reduce pulsatile flow artifacts in MR angiography. When these techniques are used in conjunction with phase contrast angiography in the extremities they can produce arterial edge artifacts. PMID- 8505868 TI - A chemical shift selective inversion recovery sequence for fat-suppressed MRI: theory and experimental validation. AB - Fat-suppression techniques are used extensively in routine proton nuclear magnetic resonance imaging to produce images free from chemical shift artifacts and dynamic range problems. A hybrid fat-suppression sequence is studied which combines the principle of short time inversion recovery with chemical shift selective imaging. The aim of this study is to provide a theoretical understanding of the role of the sequence parameters, as well as to compare this hybrid sequence with its most closely related conventional fat-suppression techniques, namely selective pre-saturation and short time inversion recovery (STIR) imaging. The hybrid technique is shown to be robust in normal use, and more tolerant than the conventional methods to mis-settings of parameters such as inversion time, as well as tip angle and frequency bandwidth of the fat selective pulse. PMID- 8505869 TI - A half-Fourier gradient echo technique for dynamic MR imaging. AB - Recently we developed the simultaneous dual FLASH (SDFLASH) pulse sequence that simultaneously obtains sequential images from the brain and the internal-carotid arteries in the neck with 1-sec temporal resolution using a standard MR scanner. The high temporal resolution (1 sec) of the SDFLASH technique was achieved partly by using a low number of phase-encoding views which thereby limited our in-plane spatial resolution to 6.25 x 3.12 mm pixels. To overcome this limitation we have developed a calibration technique which corrects distortions in signal intensity and object shape when using gradient echo half-Fourier spin warp imaging. Using this calibration technique, the operator can use the 41% decrease in scan time to either double the spatial or temporal resolution. We have successfully used this technique to acquire SDFLASH images of the head and neck with 1.0 sec temporal resolution and 3.12 x 1.6 mm spatial resolution. PMID- 8505870 TI - A new method for diffusion weighted imaging. AB - A new method for generating diffusion contrast in magnetic resonance imaging is presented. This technique is robust enough to allow implementation on conventional imaging systems without hardware modifications. Results from phantom measurements are reported. Qualitative contrast changes in magnetic resonance images derived from live mammalian brain are also demonstrated. PMID- 8505871 TI - Estimation of myocardial water content using transverse relaxation time from dual spin-echo magnetic resonance imaging. AB - Dual spin-echo magnetic resonance imaging may be used for calculation of transverse myocardial relaxation time from the signal intensity of the echoes considered. In this study, the ability of myocardial transverse relaxation time (T2) to quantitate myocardial edema of the right ventricle (RV) and left ventricle (LV) was tested. Dual spin-echo magnetic resonance images of the entire hearts were obtained and T2 of the RV and LV myocardium calculated from the signal intensities within multiple regions of interest distributed over the myocardium. Six hearts were intermittently perfused through an aortic cannula with three perfusates of decreasing osmolality. Biopsies were obtained for water content (WC) analysis both before and after imaging the hearts at baseline and post-perfusion. A seventh (control) heart was not perfused; instead dual spin echo imaging was performed at the same time intervals as in the perfused hearts. Prior to any intervention, there was no significant difference between baseline RV (79.49 +/- 2.10%) and LV (77.99 +/- 2.44%, p = .2) myocardial water content; RV myocardial T2 (59.9 +/- 5.8 msec) was slightly but not significantly longer than that of the LV (54.6 +/- 5.7 msec, p = .1). After induction of edema, strong correlation was found between right ventricular myocardial water content measurements and right ventricular T2 (RV WC = 68.5 + 0.19 x RV T2; N = 27, R = 0.92, p < .0001, SEE = 1.56%). Similarly, strong correlation was found between left ventricular myocardial water content and T2 (LV WC = 62.1 + 0.29 x LV T2; N = 27, R = 0.92, p < .0001, SEE = 1.80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505872 TI - Fat tissue and fat suppression. AB - Fat tissues consist of fat cells, capillaries, and collagen fibers. In order to completely suppress the signals from fat tissues in clinical magnetic resonance imaging, the signal from capillaries and collagen fibers as well as from fat cells should all be suppressed. We have previously reported that fat signal can be uniformly suppressed by applying an optimized presaturation pulse. The inhomogeneously broadened fat peak of tissue spectrum is excited by the optimized pulse and dephased by a subsequent field gradient. The broadened water peak is not affected. In this paper we discuss a technique that suppresses signals from fat tissues completely as well as uniformly. This technique is based on the cancellation of fat and water signals in the same image voxel by combining the optimized selective excitation with the opposite phase imaging technique. Experimental and clinical images demonstrate that the new technique improves the delineation and depiction of anatomy in clinical fat suppression imaging. PMID- 8505873 TI - Characterization of human aortic collagen's elasticity by nuclear magnetic resonance. AB - The elasticity of the human aortic wall in longitudinal uniaxial elongation at high strain, known to be determined mostly from tissular collagen's behaviour, is studied and compared to the second moment of the 1H nuclear magnetic resonance (NMR) solid state line-shape, a proton nuclear magnetic resonance (at 60 MHz) characteristic for the molecular motion and the rigidity of the collagen macromolecular backbone. The 1H NMR signal of collagen is identified after selective histologically controlled chemical lysis. The computed second moment of the line-shape shows statistically significant correlation with the slope of the strain-stress curve of the aorta at high strain, thus proving the relationship between a macroscopic tissular elasticity parameter and a macromolecular rigidity characteristic of collagen, a major tissular component. In vivo extension of this technique (e.g., MRI) would allow us to gain information on the biomechanical state of the aorta, a naturally highly stressed and strained tissue. PMID- 8505874 TI - Diffusion- and T2-weighted imaging: evaluation of oedema reduction in focal cerebral ischaemia by the calcium and serotonin antagonist levemopamil. AB - Magnetic resonance imaging (MRI) was used to evaluate beneficial drug effects in a rat model of focal cerebral ischaemia. Extent of cerebral oedema was measured on T2-weighted images 24 hr after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Areas of increased signal intensity strongly correlate with histochemically determined areas of ischaemia in corresponding brain planes (r = 0.84; p < .001). In a separate cohort of animals, spatial progression of oedema formation was studied at 3, 24, 48, and 72 hr after MCAO showing a maximum extent at 48 hr. Early events in cerebral ischaemia were monitored using diffusion-weighted imaging. Effects of levemopamil [formerly (S) emopamil], a calcium and serotonin antagonist, and the reference compound isradipine were quantified on high resolution T2-weighted spin-echo images 24 hr after MCAO. Combined pre- and posttreatment with isradipine showed a 21% inhibition of oedema progression. Application of a single dose (10 mg/kg) of levemopamil either 30 min before or 2 hr after MCAO revealed a diminution of oedematous areas by 19% and 25%, respectively. Levemopamil reduces the extent of ischaemic brain oedema in an established stroke model. PMID- 8505875 TI - Study of the membrane permeability of a paramagnetic metal complex on single cells by NMR microscopy. AB - A new procedure has been developed for investigating the ability of paramagnetic metal complexes to penetrate the plasma membrane of eukaryotic cells without decomposition. Defolliculated Xenopus laevis oocytes formed the biological system to test N,N-ethylenebis-(1,5,5-trimethyltetramic-acid-3-acetiminato) copper (II). An increase of the signal intensities in spin-echo (SE) images of oocytes treated with the tested substance indicated that the complex was able to penetrate biological membranes due to the arrangement of hydrophobic and hydrophilic groups within the ligand. In contrast, the treatment with the commonly used contrast agent gadolinium-DTPA/dimeglumine did not enhance the signal intensity in NMR images of oocytes after time periods of exposure comparable to those used for the copper complex. After microinjection into Xenopus oocytes the copper complex was released into the extracellular medium without degradation, as shown by HPLC measurements. PMID- 8505876 TI - Signal-to-noise measures for magnetic resonance imagers. AB - The signal-to-noise ratio (SNR) in magnetic resonance imaging represents one of the system operating variables that must be determined both for evaluating the performance of different imaging protocols on a particular machine, and for monitoring machine performance as part of a routine quality control (QC) program. Utilizing a phantom and set of automated analysis programs currently under development, this study evaluated several ways of measuring image signal and noise and demonstrated the importance of utilizing measured voxel volumes as opposed to nominal volumes in the calculation of SNR. The NEMA proposed standard for SNR is compared with several other SNR measures and is recommended as the measure to be used in routine SNR reporting. The importance of utilizing other SNR measures in addition to the NEMA proposed standard for routine QC is discussed. PMID- 8505877 TI - Three dimensional MR gradient recalled echo imaging of the inner ear: comparison of FID and echo imaging techniques. AB - The detailed structures of the inner ear make this region a diagnostic challenge for radiologists. Thin section high resolution CT is the "gold standard" for studies of the fine bony detail of the inner ear. Although CT can delineate bony structures, fine soft tissue details surrounded by CSF/endolymph (such as nerves in the internal auditory canal) are not easily identified. Conventional MR spin echo T2-weighted images provide good image contrast for such structures, but the current commercially available minimum slice thickness of approximately 2-3 mm is too thick for the inner ear. Volume gradient recalled echo (GRE) MR imaging techniques can be used to achieve thin slices (< 2 mm) while maintaining adequate contrast for detailed examination. In the work reported here a volume GRE sequence that images the echo formed in a steady-state-free-precession (termed "CE-FAST" or "SSFP" on various commercial MRI systems and called SSFP-echo in this work) was used to image inner ear structures. This technique was compared with images generated using conventional volume GRE techniques (GRASS). While small flip angle volume GRE imaging has been used for inner ear imaging previously, the low contrast typical of such density weighting makes it difficult to distinguish soft tissue structures from surrounding CSF/endolymph. In this work, contrast-to-noise ratios (CNR) between CSF/endolymph and brain parenchyma were compared between the sequences at 15 degrees, 30 degrees, 60 degrees, and 90 degrees flip angles. The SSFP-echo sequence produced higher CNR for such structures and consistently outperformed GRASS sequences at flip angles of 30 degrees, 60 degrees, and 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8505878 TI - Radiofrequency map of an NMR coil by imaging. AB - We propose a new imaging method to obtain a map of the radiofrequency (RF) field amplitude over a sample. The sequence contains three RF pulses (alpha, 2 alpha, and alpha) and produces two images by a classical spin echo and a stimulated echo. A third image is computed and gives the distribution of the flip angle alpha, and so the RF amplitude, over the sample. The accuracy of the flip angle determination is verified on an homogeneous sample and results show a good correlation between experimental and theoretical flip angles in the range of 50 degrees to 130 degrees. Experiments with a surface coil and a resonator show the method is available in an inhomogeneous RF field. Images obtained on the calf of a volunteer confirms the independence of the computed RF distribution from proton density, T1, or T2 contrast. PMID- 8505879 TI - Intracranial tuberculomas: MRI signal intensity correlation with histopathology and localised proton spectroscopy. AB - In seven cases of intracranial tuberculomas showing different signal intensities on MRI (five characteristic and two nonspecific), detailed histopathological examination was performed to look for number of macrophages, fibrosis, gliosis, degree of inflammatory cellular infiltrate, and type of caseation. The granulomas showing more macrophages, fibrosis and gliosis appeared hypointense on T2 weighted images. Tuberculomas showing minimal macrophages, marked cellular infiltration, and minimal fibrosis appeared hyperintense on T2-weighted images. Lesions showing similar signal intensity on T2-weighted images showed variation in the amount of macrophages, cellular infiltrates, maturity and fibrosis. Trace element estimation was done (iron, copper, and magnesium) in two of these lesions appearing hypointense on T2 and two normal brain samples; these were significantly lower in tuberculoma compared to normal brain tissue. Localised proton spectroscopy was performed in two hypointense lesions which showed marked increase in peaks in the region of mobile lipids (1.28 ppm) compared to normal brain parenchyma. It is concluded that the signal intensity of the lesions is dependent on the number of macrophages, fibrosis and cellular infiltrates. In addition increased lipid contents in the tuberculoma also contribute to the hypointensity on T2-weighted images. PMID- 8505880 TI - [Rotavirus gastroenteritis in a pediatric service at the National University Hospital Center of Cotonou (Benin)]. AB - The authors are reporting results from rotavirus research in diarrhoeal stools among 220 children under 5 years of age in Cotonou C.N.H.U. (Benin). Among them, 64 (29%) are rotavirus carriers. PMID- 8505881 TI - [Refinement of a biological procedure for the control of mosquitos, vectors of endemic diseases in Central Africa]. PMID- 8505882 TI - [From the navy to colonial troops: the birth of the Pharo School. Auguste and Louis Thoulon]. PMID- 8505884 TI - [Ankylosing spondylarthritis: first case described in Gabon]. AB - The first case of ankylosing spondylitis described in Gabon is reported here. The patient was a 32 years old and presented an advanced typical form. Test for HLA B27 was negative. The rarity of this disease among black Africans is explained by the low prevalence of the antigen. PMID- 8505883 TI - [Study of antibiotic sensitivity of Streptococcus pyogenes isolated in the hospital milieu (Charles Nicolle hospital of Tunis)]. AB - The purpose of the present work was to investigate the susceptibility of S. pyogenes to antimicrobial agents. The strains have been taken from the bacteriological Service of Charles Nicolle's hospital at Tunis, and that during the period from January 1988- to December 1990. The antibiogram results as well as the minimal inhibitrice concentration determined by the agar diffusion technique, reveal that S. pyogenes continues to be very susceptible to the beta lactamins (M.I.C. of penicillin G is "0.15 for 50% of strains tested. Resistance are noted for chloramphenicol; tetracycline and novobiocine (13%, 93%, 80%) not considered as good antibiotics anti-streptococcies. The macrolids are effective against S. pyogenes (100% of susceptibility) that's they are considered as the best alternating antimicrobiologents to the beta-lactamins (M.I.C. of erythromycin is 0.015. PMID- 8505885 TI - [Ocular pathology in the rain forest (Cameroon)]. AB - In June 1988, a survey including 1,076 persons was carried out in the rural areas of the Littoral Province to study the distribution of eye diseases and from there determine the needs of the rural population with respect to eye care. The most frequent ophthalmological problems, apart from refraction errors, were found to be onchocerciasis and cataract. Our study shows that onchocerciasis found in the rainforest of Littoral province causes blindness as much as that found in the savannah: it was the principal cause of bilateral blindness (66.4%) in the study. Knowing that about 200,000 onchocerciasis patients with a considerable risk of becoming blind, live in the rural areas of Littoral, a programme of detection and treatment of this disease with Ivermectine was introduced since 1989. PMID- 8505886 TI - [Ancient serological traces of infections by the human immunodeficiency virus HIV 1 and HIV-2 in sub-saharan Africa. A different geography]. AB - Despite of some heavy methodological limitations, the analysis of some serological data collected before 1985 allows to establish the selective regional distribution of the two infections. HIV-2 is prevalent in the West African sites which are studied and he has been observed since the sixties. The foci and the sporadic cases of the HIV-1 which are known are localized principally in the East Central Africa. (Research done under the sponsorship of the A.N.R.S. (Paris)). PMID- 8505887 TI - [The pathogenicity of the human immunodeficiency virus HIV-2 as seen by epidemiologists]. AB - The purpose of this study is an evaluation of HIV-2 pathogenicity through an epidemiological analysis, specially in Africa. It is acknowledged that the incubation, or more specially the lapse of time between the infection and the AIDS disease, is longer with HIV-2 than with HIV-1. More over, a certain number of surveys done in Africa show that the average age is higher with HIV-2 than with HIV-1; this is a regular sign of lower pathogenicity. It appears that the sexual transmission of the virus is the same for the HIV-2 and the HIV-1, but it is less effective from mother to baby. Furthermore this type of virus is less prevalent with AIDS patients or AIDS suspects than the HIV-1; and the follow-up of HIV-2 seropositives show that fewer people fall ill than with the HIV-1. A few signs of AIDS standard diagnosis are less frequent among HIV-2 infected patients than among HIV-1 infected patients. Opportunist or associated infections, like tuberculosis or malnutrition, are less often found in HIV-2 patients. PMID- 8505888 TI - [Retrospective diagnosis of anthrax by intradermal reaction]. AB - The authors report a detailed study of utilization of a skin test with anthraxin to perform a retrospective diagnosis of anthrax in humans who suffered from anthrax 45 days to 31 years after recovery. For a total of 884 persons studied, 762 showed a positive skin test (86.2%). This index was 92.8% for persons tested 45 days to 3 years after convalescence, 82.8% 4 to 15 years after convalescence and 72.7% 16-31 years after recovery. The site of the primary carbuncle on the skin of the fingers, hands, face and neck gave an index of positivity (88.2%) statistically greater (p = 99%) than by localization of the carbuncle on arms, forearms, trunk and legs (77.3%). PMID- 8505889 TI - [Infection by the human immunodeficiency virus in the Republic of Djibouti: literature review and regional data]. AB - The first evidence of HIV infection in Djibouti, East Africa, was found in the spring of 1986; the first case of acquired immunodeficiency syndrome (AIDS) was diagnosed in March 1988; and, as of the end of 1991, 104 cases of AIDS had been reported. HIV-1 infection was predominant. Previously published results of four serosurveys carried out in October 87, June 1998, February 1990, and from January 1991 to April 1991 among high risk groups are presented and compared. The subjects included street girls, bar hostesses, and male STD patients. HIV-1 infection was demonstrated in 1991 among 36.0% of street girls, 15.3% of bar hostesses and 10.4% of male STD patients. Three sera were positive for both HIV-1 and HIV-2 antibodies. The prevalence of HIV-1 infection among street girls in Djibouti did not increase between February 1990 and January 1991 while the prevalence of HIV infection among male STD patients rose almost five-fold during the same period. HIV prevalence in bar hostesses showed a steady growth. Epidemiology of HIV infection among prostitutes is complex as theses populations have a rapid turn-over. HIV prevalence data and predominance of Ethiopian nationality among prostitutes suggest importation of HIV from Ethiopia via the prostitutes and their clients. These results are reviewed and compared with data from Ethiopia and Somalia. PMID- 8505890 TI - [Towards dracunculosis eradication in Cameroon?]. AB - Dracunculiasis is endemic in the Mayo-Sava region, Province of Extreme North, Cameroon. Its incidence has been reduced by half (from 778 cases in 1990 to 394 cases in 1991) thanks to the national eradication program (wells, distribution of filters, use of temephos to treat water collections, sanitary education, cases containment). PMID- 8505891 TI - [A rare cause of intestinal obstruction revealed during pregnancy (Kamenge University Hospital Center, Bujumbura, Burundi)]. AB - Acute intestinal occlusion is rare during pregnancy, and more exceptional is the source itself of the occlusion we are reporting embryonic. This is actually an embryonic remains: the omphalo-mesenteric (vitellin) duct that did not resorb and has developed into a fibrous cord. The latter, owing to physiological modifications, is responsible of the occlusion. The authors analyse the two facts which, when associated, represent an interesting clinical fact. PMID- 8505893 TI - Noninvasive observation of hepatic glycogen formation in man by 13C MRS after oral and intravenous glucose administration. AB - The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C magnetic resonance spectroscopy (MRS) under two different conditions: a) intravenous infusion of [1-13C]glucose under hyperglycemic and hyperinsulinemic clamp conditions, and b) oral intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of alpha- and beta-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by 13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 +/- 34 mM (minimum = 160 mM; maximum = 274 mM). PMID- 8505892 TI - [Malaria and post operative fever in the University Hospital Center of Yaounde (Cameroon)]. AB - This study from a series of 80 patients showed that the prevalence rate of malaria increased from 8% before to 15% after surgery in the tropics. The difference was not significant (p < 0.05). The conclusion is that patients should be investigated for malaria parasites before any major surgery; in case of a non infectious post-operative fever, antimalarial drugs should be prescribed only to patients with a positive thick film. PMID- 8505894 TI - A knowledge-based approach to minimize baseline roll in chemical shift imaging. AB - A method has been developed to minimize baseline roll in chemical shift imaging (CSI). The technique is fully automated and employs knowledge based data processing in the frequency domain. The key feature of the algorithm is the computation of the "trough" and "ripple" components in the CSI data. The baseline roll can be regarded as an artifact that appears as a result of the summation of several sinc functions. Using prior knowledge, a mirror component corresponding to the artifact is created and added to the delayed spectrum. The method compensates for noise and zero-order phase error when computing the roll artifact. The results obtained on implementing the baseline roll minimization procedure on simulated time-delayed spectra indicated that the peak heights and areas were between 91% and 97% in magnitude when compared with the same peaks in the nondelayed spectra. The correction procedure was also assessed on clinical in vivo spectra. Nonlocalized 31P MR spectra of the liver were obtained with and without an acquisition delay of 2.1 ms, and the time delayed spectra subjected to the baseline minimization routine. Metabolite peak heights and areas in the corrected spectra were approximately 94% in magnitude when compared with the same peaks in the original nondelayed whole volume spectra. Implementation of the baseline minimization procedure on in vivo localized spectra with varying signal to noise ratios produced good results. It takes approximately 13 s to implement the baseline roll minimization procedure. In this paper, the technique will be referred to as BaseLine Artifact Suppression Technique (BLAST) routine. PMID- 8505895 TI - Monocrystalline iron oxide nanocompounds (MION): physicochemical properties. AB - We have previously described a novel monocrystalline iron oxide nanocompound (MION), a stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using a variety of analytical techniques. High resolution electron microscopy indicates that a MION consists of hexagonal shaped electron-dense cores of 4.6 +/- 1.2 nm in diameter. This iron oxide core has an inverse spinel crystal structure which was confirmed by x-ray powder diffraction. Chemical analysis showed that each core has 25 +/- 6 dextran molecules (10 kD) attached, resulting in a unimodal hydrodynamic radius of 20 nm by laser light scattering. Because of the flexibility of the dextran layer, the radius is only 8 nm in nonaqueous reverse micelles. At room temperature, MION exhibit superparamagnetic behavior with an induced magnetization of 68 emu/g Fe at 1.5 T. Mossbauer studies show that the saturation internal magnetic field is 505 KOe, and blocking temperature is at 100 K. The R1 relaxivity of MION is 16.5 (mM.sec)-1 and the R2 relaxivity is 34.8 (mM.sec)-1 in aqueous solution at 37 degrees C and 0.47 T. In vitro phantom studies show that the detectability of MION in liver tissue is less than 50 nmol Fe/g tissue using gradient echo imaging techniques. PMID- 8505896 TI - Resting and end-diastolic [Ca2+]i measurements in the Langendorff-perfused ferret heart loaded with a 19F NMR indicator. AB - Intracellular free calcium concentration ([Ca2+]i) was measured in Langendorff perfused ferret hearts (30 degrees C, pH 7.4) by loading paced hearts with the 19F NMR calcium indicator, the 5,5'-difluoro derivative of 1,2-bis(o aminophenoxy)ethane-N, N,N',N'-tetraacetic acid (5FBAPTA), to an initial cytosolic concentration of approximately 120 microM. Increasing the pacing frequency raised the end-diastolic [Ca2+]i from 299 +/- 44 nM (mean +/- SEM) at 0.2 Hz to 522 +/- 54 nM at 1.0 Hz and 691 +/- 166 nM at 2.0 Hz. Raising [Ca]o from 1.8 to 7.0 mM at a pacing frequency of 1.0 Hz increased end-diastolic [Ca2+]i to 625 +/- 39 nM. In unpaced hearts perfused with diltiazem (100 microM), [Ca2+]i fell rapidly to a steady-state value of < 100 nM after 60 min. Raising [Ca]o from 1.8 to 7.0 mM had no detectable effect on resting [Ca2+]i. The time course of the [Ca2+]i transient was measured in hearts paced at 1.1 Hz and perfused with 1.8 mM [Ca]o. The peak [Ca2+]i was approximately 2 microM at approximately 150 msec after the pacing pulse, and peak developed LVP occurred at 550 msec compared with 280 msec in control hearts not loaded with 5FBAPTA. Comparisons with data obtained by other techniques, including fluorescent [Ca2+]i indicators, imply that although the end-diastolic [Ca2+]i values obtained with 5FBAPTA in beating hearts are elevated by the concentrations of intracellular 5FBAPTA required for signal detection, the changes in [Ca2+]i observed in response to experimental interventions are qualitatively consistent with previous data. PMID- 8505897 TI - Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative noninvasive technique. AB - A simple, linear kinetic model has been developed for the noninvasive assessment of capillary permeability to macromolecules in the rat by dynamic magnetic resonance imaging using albumin-Gd-DTPA. Data required by the model are signal intensity responses from a target tissue and a venous structure such as inferior vena cava before and after bolus intravenous injection of albumin-Gd-DTPA. Additional requirements include an early temporal resolution of approximately one image/min and a blood sample for hematocrit. The model does not require measurement of albumin-Gd-DTPA concentration in either arterial or venous blood. Pilot experiments suggest that this technique is adequate for estimation of the fractional leak rate of macromolecules from plasma to interstitial water as well as tissue plasma volume, the product of which yields a measure of the permeability surface area product of the tissue if the extraction fraction is modest (< 0.2). The technique may be generally applicable to the study of abnormal capillary permeability in humans as well as animals. PMID- 8505898 TI - A multispectral analysis of brain tissues. AB - With the increasing use of three-dimensional MRI techniques it is becoming necessary to explore automated techniques for locating pathology in the volume images. The suitability of a specific technique to locate and identify healthy tissues of the brain was examined as a first step toward eventually identifying pathology in images. This technique, called multispectral image segmentation, is based on the classification of tissue types in an image according to their characteristics in various spectral regions. The spectral regions chosen for this study were the hydrogen spin-lattice relaxation time T1, spin-spin relaxation time T2, and spin density, rho. Single-echo, spin-echo magnetic resonance images of axial slices through the brain at the level of the lateral ventricles were recorded on a 1.5 Tesla imager from 20 volunteers ranging in age from 17 to 72 years. These images were used to calculate the T1, T2, and rho images used for the classification. Tissue classification was performed by locating clusters of pixels in a three-dimensional T1(-1)-T2(-1)-rho histogram. Gray matter, white matter, cerebrospinal fluid, meninges, muscle, and adipose tissues were readily classified in magnetic resonance images of the volunteers with a single set of T1, T2, and rho values. Cluster characteristics, such as size, shape, and location, provided information on the imaging procedure and tissue characteristics. PMID- 8505899 TI - Continuous inversion angiography. AB - A subtractive time-of-flight technique for magnetic resonance angiography is described. In this approach, the arterial supply to an organ is inverted in a steady-state fashion by applying off-resonance irradiation in the presence of a linear magnetic field gradient. An angiogram is formed by subtracting an image acquired with arterial inversion from a control image acquired with no arterial inversion. A single coil is used to apply both the inversion and observation pulses. Intracranial angiograms obtained from normal volunteers using a two dimensional projective implementation of this technique at 1.5 T illustrate excellent small vessel detail and background suppression. PMID- 8505900 TI - On the use of Bayesian probability theory for analysis of exponential decay data: an example taken from intravoxel incoherent motion experiments. AB - Traditionally, the method of nonlinear least squares (NLLS) analysis has been used to estimate the parameters obtained from exponential decay data. In this study, we evaluated the use of Bayesian probability theory to analyze such data; specifically, that resulting from intravoxel incoherent motion NMR experiments. Analysis was done both on simulated data to which different amounts of Gaussian noise had been added and on actual data derived from rat brain. On simulated data, Bayesian analysis performed substantially better than NLLS under conditions of relatively low signal-to-noise ratio. Bayesian probability theory also offers the advantages of: a) not requiring initial parameter estimates and hence not being susceptible to errors due to incorrect starting values and b) providing a much better representation of the uncertainty in the parameter estimates in the form of the probability density function. Bayesian analysis of rat brain data was used to demonstrate the shape of the probability density function from data sets of different quality. PMID- 8505901 TI - Nontriggered magnetic resonance velocity measurement of the time-average of pulsatile velocity. AB - The feasibility of the determination of the time-average of pulsatile velocity obtained via a nontriggered magnetic resonance (MR) acquisition is studied. The advantage of this method, in comparison with a triggered acquisition, is a considerable reduction (approximately 15x) in acquisition time. However, pulsatility causes image artifacts, known as ghosts, and the Fourier transform technique required for the imaging procedure accomplishes time-averaging of the complex MR signal. Both effects can result in errors in the velocity determined. Calculations show that these errors depend on the velocity time function and the acquisition parameters. In vivo comparison of triggered and nontriggered MR velocity measurements in the femoral artery of volunteers (n = 7) shows larger statistical and systematic errors in the latter, which depend on the excitation angle. Therefore, this nontriggered average velocity measurement is only useful as a fast and rough estimation of the time-averaged velocity. PMID- 8505902 TI - In vivo 1H chemical shift imaging of silicone implants. AB - In order to study the aging process (i.e., silicone migration, fat infiltration) of silicone (polydimethylsiloxane, PDMS) based biomaterials in living subjects by NMR imaging, a hybrid 1H selective excitation and saturation chemical shift imaging technique (IR/CHESS-CSSE) has been developed. This sequence allows selective mapping of the distribution of silicone protons in vivo, while suppressing the contributions of fat and water. Our results indicate that a combined inversion recovery and CHESS pulse, followed by a spoiler gradient, must be applied to suppress all contributions of fat protons to the NMR signal. The sensitivity of our experiments allows the detection of a chemically unchanged silicone concentration of 5% in a voxel of 0.9 mm3 at a signal/noise ratio of 2. PMID- 8505903 TI - Real-time acquisition, display, and interactive graphic control of NMR cardiac profiles and images. AB - A highly interactive MRI scanner interface has been developed that allows, for the first time, real-time graphic control of one-dimensional (1D) and two dimensional (2D) cardiac MRI exams. The system comprises a Mercury array processor (AP) in a Sun SPARCserver with two connections to the MRI scanner, a data link that passes the NMR data directly to the AP as they are collected, and a control link that passes commands from the Sun to the scanner to redirect the imaging pulse sequence in real time. In the 1D techniques, a cylinder or "pencil" of magnetization is repeatedly excited using gradient-echo or spin-echo line-scan sequences, with the magnetization read out each time along the length of the cylinder, and a scrolling display generated on the Sun monitor. Rubber-band lines drawn on the scout image redirect the pencil or imaging slice to different locations, with the changes immediately visible in the display. M-mode imaging, 1D flow imaging, and 2D fast cardiac imaging have been demonstrated on normal volunteers using this system. This platform represents an operator-"friendly" way of directing real-time imaging of the heart. PMID- 8505904 TI - High-precision MR velocity mapping by 3D-Fourier phase encoding with a small number of encoding steps. AB - The final result of Fourier velocity mapping is a set of images, each representing the spatial distribution of spins at a given velocity. To acquire data in a short time, the number of encoding gradient steps must be as small as possible, but this can mean sacrificing velocity resolution. We used interpolation methods to obtain high velocity resolution with a small number of encoding steps involving linear interpolation from 16 encoding steps or more and zero-filling interpolation from two to eight encoding steps. Velocity measured by interpolated Fourier-flow encoding agreed well with values obtained using a calibrated phantom. A simulation of noise on the images of the phantom showed that, for a given acquisition time, increasing number of encoding steps in the Fourier flow encoding gave better precision for velocity measurement than did averaging identical signals in phase-mapping methods. PMID- 8505905 TI - Imaging time reduction through multiple receiver coil data acquisition and image reconstruction. AB - A technique is described for the simultaneous acquisition of MRI data using two independent receiver coils surrounding the same region of tissue, which enables the collection of data necessary for image reconstruction in a reduced number of phase-encoded acquisitions. This results in a 50% reduction in minimum scan time and may be useful in time-critical procedures. The algorithm and imaging procedures are described, and example images are shown that illustrate the reconstruction. Signal to noise is decreased by the square root of the time savings, making this technique applicable to cases in which the need to decrease minimum scan time outweighs the signal to noise penalty. PMID- 8505906 TI - Measurement of T1 relaxation times of cardiac phosphate metabolites using BIR-4 adiabatic RF pulses and a variable nutation method. AB - T1 relaxation times of PCr and beta-ATP in human cardiac and skeletal muscle were evaluated using a variable nutation method. This allows T1 measurements with a constant TR and a significant reduction in acquisition time compared with the partial saturation method. Four 1D CSI datasets were obtained using 30 degrees, 45 degrees, 60 degrees, and 90 degrees BIR-4 adiabatic RF pulses within 40 min. The T1 of the phosphate phantom obtained with this method agreed with values obtained with the partial saturation method. The T1s of PCr and beta-ATP in heart are 3.98 +/- 0.18 s and 1.86 +/- 0.16 s (mean +/- SE). Our results demonstrated that T1 values in heart and skeletal muscle are not significantly different. PMID- 8505907 TI - N-acetyl-L-aspartate and acetate 1H NMR signal overlapping under mild acidic pH conditions. AB - The pH dependence of methyl proton chemical shifts of acetate, acetoacetate, N acetyl-L-aspartate (NAA), and N-acetyl-L-aspartyl-L-glutamate (NAAG) were studied from pH 3 to pH 9. Only slight shifts of acetoacetate, NAA, and NAAG methyl signals were observed, whereas the acetate signal was largely shifted as a result of the titration of its acidic function. At pH 4.7, acetate and NAA methyl signals overlapped, whereas at more acidic pH, the acetate signal appeared downfield when compared to that of NAA. Results are discussed in terms of spectra misinterpretation risks linked to uncontrolled sample pH, on the one hand, and in terms of pH control and contamination by exogenous acetate during perchloric acid cell extract preparation, on the other. PMID- 8505908 TI - Optimization of flip angle for T1 dependent contrast in MRI. AB - The flip angle which maximizes contrast between materials with different T1 can be calculated from the root of a cubic expression. A simple closed form expression can be used if contrast is defined in a differential sense and results in only slight contrast loss even with large T1 differences. PMID- 8505909 TI - Susceptibility changes following bolus injections. AB - The general mechanism of bulk magnetic susceptibility (BMS) induced MRI contrast following a bolus injection is elaborated. Combining radiolabeled tracer data for the first pass of a bolus injection through the human brain with the application of Wiedemann's law allows us to calculate the lower limit for the time course of the vascular BMS following the injection of any contrast agent. Superparamagnetic iron oxide particles produce a much larger effect than any mononuclear Ln(III) chelate. We also calculate the BMS changes occurring after a dilution bolus injection (of isosmolal physiological saline) subsequent to a prior slow infusion of an intravascular contrast agent. This technique bears some resemblance to the increasingly important approach that exploits changes in only the level of blood oxygenation. The calculation indicates that contrast changes after the dilution bolus injection are smaller than those following Ln(III) agent injections but larger than those due to changes in blood oxygenation and suggests a way to possibly enhance the latter. We present an in vivo study demonstrating the dilution bolus injection technique in the mouse brain, and that features its rapid repeatability. Extrapolation of these results to the human, however, indicates that the saline volumes required for venous injections, except possibly for cardiac studies, would be prohibitively large. Smaller, catheter-delivered arterial bolus injections are feasible. We also suggest a method for using an agent bolus injection to measure the parenchymal BMS, and thus the iron content, of pathologically iron-loaded tissue. PMID- 8505910 TI - Quantification of regional blood volumes by rapid T1 mapping. AB - A new method is presented for the quantitative determination of regional blood volumes in vivo. It is based on rapid quantitative T1 mapping by Snapshot FLASH MRI combined with the injection of an intravascular MR contrast agent. Regional blood volumes in four different tissues of the rat (skeletal muscle, heart, liver, kidney) were determined in an in vivo experiment. PMID- 8505911 TI - Radiative losses of a birdcage resonator. AB - We present a derivation of the losses in a birdcage resonator due to radiation. We also present an expression for the radiation limited Q. It is shown that in head coil imaging at 63 MHz radiative losses may account for 20% of the total loss with a radiation limited Q on the order of 150. The results are shown to be consistent with those reported in the recent literature. PMID- 8505912 TI - [Role of the energy status and putrescine transport in the maintenance of the intracellular pH homeostasis in the course of alkaline and acidic shifts in Escherichia coli]. AB - Alkaline and acidic shifts in exponentially grown Escherichia coli cultures were accompanied by an abatement of the cell energetic status (decline of ATP and energy charge and increase of the ADP and AMP pools). This event led to a suspension of the growth at (the means of) pH 9.0 and 6.0 accordingly. An increment of ornithine decarboxylase activity and an efflux of putrescine from the cells were observed in the course of alkaline shift. Environmental acidification was accompanied by intensification of the cell respiration rate and H+ATPase activity in the absence of the putrescine efflux from the cells. The involvement of the polyamine synthesizing system in the regulation of cell K+ content and the role of the primary proton pumps in the maintenance of pH homeostasis are discussed. PMID- 8505913 TI - [Stimulatory effect of serotonin on the growth of the yeast Candida guilliermondii and the bacterium Streptococcus faecalis]. AB - Periodic addition of serotonin into a cultivation medium during growing of the yeast Candida guilliermondii and the bacterium Streptococcus faecalis exerts stimulatory influence on the growth of the cultures. The effect manifests itself in activating cell reproduction in the lag-phase, accelerating exponential growth of the cultures and their quicker reaching the stationary phase. The stimulatory effect of serotonin is optimal if serotonin is added to the growth medium at concentrations up to 10(-7) M with a periodicity of 2 hours. PMID- 8505914 TI - Are you ready for an encounter with the board of medical practice? PMID- 8505915 TI - Shape up! Physicians prod patients to give up bad habits. PMID- 8505916 TI - Medicine for a sick immunization system. AB - The United States has recently experienced a rise in the incidence of measles and other preventable infectious diseases. Studies have linked the problem to a growing number of inadequately vaccinated preschoolers. The Minnesota Department of Health estimates that only 61.4% of the state's 2-year-olds have completed the basic primary series on schedule. Coverage rates are worse in the Twin Cities, where the number of poor and minority "at-risk" children has skyrocketed in the last 10 years. Two different assessments in St. Paul revealed that only 24% to 32% of the 2-year-olds in the survey populations had received the basic series of immunizations. Public and private health care providers need to work together to eliminate barriers to immunization. PMID- 8505917 TI - Chemical dependency allegations and the Minnesota Board of Medical Practice. PMID- 8505918 TI - Physician, market thyself. A patient relations primer. PMID- 8505919 TI - Health reform appears threatening but offers opportunity. PMID- 8505920 TI - HIV never dormant. PMID- 8505921 TI - Suit filed over AIDS coverage. PMID- 8505922 TI - Adolescent health. A target for preventive health measures. PMID- 8505923 TI - The Board of Medical Practice. Can it protect the public and meet physician needs? PMID- 8505924 TI - Ask the nurse attorney. Patient Self Determination Act of 1990. PMID- 8505925 TI - Insurance pool covers uninsurable. PMID- 8505926 TI - Sharing the vision: Mississippi nursing revisited. PMID- 8505927 TI - Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome. AB - Myasthenia gravis can present with rapid respiratory failure as the first manifestation of disease. In the Lambert-Eaton myasthenic syndrome (LEMS), such a manifestation has rarely been reported. We are reporting a patient who developed respiratory failure as the first manifestation of LEMS without associated carcinoma. PMID- 8505928 TI - Effects of chronic electrostimulation on rat soleus skinned fibers during hindlimb suspension. AB - In order to counteract the changes of the contractile properties of the rat soleus occurring during 10 days of hypokinesia-hypodynamia, due to hindlimb suspension (HS), two different patterns of electrostimulation were applied to the tibial nerve. The contractile properties of single chemically skinned muscle fibers were investigated using the tension-pCa relationship characteristics, the similar or different calcium and strontium affinities, and by measuring the P/tmax kinetic parameters. Our results showed that a pattern similar to firing rates of motoneurons innervating slow twitch muscles inhibited the slow to fast fiber changes observed during HS, whereas a pattern similar to firing rates of motoneurons from fast twitch muscles seemed to favor these changes. Since neither pattern maintained the isometric contractile force developed by the soleus fibers, we concluded that the decrease in mechanical strains imposed on the muscle during unloading was the main factor for the development of atrophy, while the kinetic changes might be predominantly modulated by the nervous command. PMID- 8505929 TI - Far-field potentials in cylindrical and rectangular volume conductors. AB - The occurrence of a transient dipole is one method of producing a far-field potential. This investigation qualitatively defines the characteristics of the near-field and far-field electrical potentials produced by a transient dipole in both cylindrical and rectangular volume conductors. Most body segments of electrophysiologic interest such as arms, legs, thorax, and neck are roughly cylindrical in shape. A centrally located dipole generator produces a nonzero equipotential region which is found to occur along the cylindrical wall at a distance from the dipole of approximately 1.4 times the cylinder's radius and 1.9 times the cylinder's radius for the center of the cylinder. This distance to the equi-potential zone along the surface wall expands but remains less than 3.0 times the cylindrical radius when the dipole is eccentrically placed. The magnitude of the equipotential region resulting from an asymmetrically placed dipole remains identical to that when the dipole is centrally located. This behavior is found to be very similar in rectangular shallow conducting volumes that model a longitudinal slice of the cylinder, thus allowing a simple experimental model of the cylinder to be utilized. Amplitudes of the equipotential region are inversely proportional to the cylindrical or rectangular volume's cross-sectional area at the location of dipolar imbalance. This study predicts that referential electrode montages, when placed at 3.0 times the radius or greater from a dipolar axially aligned far-field generator in cylindrical homogeneous volume conductors, will record only equipotential far-field effects. PMID- 8505930 TI - Acute morphologic changes in orbicularis oculi muscle after doxorubicin injection into the eyelid. AB - This study attempts to gain a better understanding of the primary cause of doxorubicin myotoxicity to aid in the development of a protocol to increase its effectiveness in treating muscle spasm diseases. The time course of acute injury to the orbicularis oculi muscle after injection of doxorubicin into the eyelids of rabbits was examined. The effects of doxorubicin injection were immediate and dramatic. Within 5 minutes, the muscle cells in the eyelids showed signs of myofibrillar dissolution. This process continued for the first 24 hours, with a marked decrease in the total number of myofibers by 1 hour after drug treatment. By 4 days after doxorubicin injection, most of the treated muscle had a more normal morphology, although some ongoing myofibrillar dissolution was present. There was evidence for a limited amount of muscle regeneration. Three levels of injury were seen: a severe, irreversible injury in the majority of the myofibers; a mild, reversible injury in a subset of the fibers; and a group of myofibers apparently uninjured as a result of doxorubicin treatment. Doxorubicin toxicity in skeletal muscle is of rapid onset. Understanding the primary cause and acute changes in doxorubicin myotoxicity may accelerate the development of improved protocols to increase the effectiveness of doxorubicin in treating muscle spasm diseases. PMID- 8505931 TI - Axonal form of Guillain-Barre syndrome: evidence for macrophage-associated demyelination. AB - We report on the clinical, electrophysiological, and pathological findings in a patient with pure motor and axonal Guillain-Barre syndrome, who died 29 days after onset. There was marked reduction of compound motor action potential amplitudes and denervation potentials in the tibialis anterior muscle. Motor and sensory conduction velocities of median nerve were normal. Peroneal nerve was inexcitable at the ankle but its latency from knee to tibialis anterior was normal. F waves were absent or delayed. The major burden of pathological changes fell on ventral spinal roots. Fundamental lesions included segmental demyelination, axonal degeneration, widespread endoneurial lipid-laden macrophage infiltrates, remyelination, and clusters of small regenerating fibers. These findings suggest that axonal damage in the axonal form of Guillain-Barre syndrome is secondary to demyelination. PMID- 8505932 TI - Assessment of diabetic neuropathy: definition of norm and discrimination of abnormal nerve function. AB - One hundred one normal subjects and 46 patients were investigated. Various objective and subjective tests for polyneuropathies were compared. Motor and sensory nerve conduction velocities are the most sensitive tests. In normals, age hardly influenced nerve conduction velocities. This is believed to be a result of the strict exclusion criteria. Diagnostic sensitivity is also high with the vibration fork test and with vibratometry at the big toe. Results with the method of limits are as reliable and sensitive as more cumbersome techniques, such as the titration method and the forced choice method. Thermal thresholds and cardiovascular tests are less sensitive. The most correct overall classification is attained with a combination of tests reflecting the function of different nerve fiber classes in the peripheral and autonomic nervous systems. PMID- 8505933 TI - Recovery of muscle after different periods of denervation and treatments. AB - Three aspects of reinnervation and recovery of skeletal muscle following various periods of denervation were investigated: (1) the effect of duration of denervation; (2) the effect of hyperthyroidism on recovery; and (3) whether the muscle or the nerve limits recovery. The rat medial gastrocnemius (MG) nerve was cut and then resutured after 0, 3, 7, 21, or 56 days. In a second group of animals, the MG muscle was denervated and, in addition, the animal received triiodothyronine (T3) supplementation during reinnervation. The third group of animals had the denervated MG muscle reinnervated by a larger number of newly transected foreign axons. The force produced by the reinnervated muscle depends on the period that the muscle was denervated. Recovery was impaired when the period of denervation exceeded 7 days. T3 treatment did not benefit the return of force production, nor did providing the muscle with a larger number of newly transected axons. PMID- 8505934 TI - Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy. AB - Abnormal carnitine distribution in muscle was found in 22 of 77 patients (29%), with mitochondrial myopathy. Furthermore, total (TC) and free (FC) carnitine levels in muscle were lower in patients than in controls (P < 0.01). Muscle long chain acylcarnitines (LCAC) were significantly increased in these patients (P < 0.01). Muscle carnitine deficiency was found in 31.5% of patients with lipid storage myopathy (LSM) and in 25.6% of patients with ragged-red fibers (RRF). Therefore, carnitine deficiency can be found in patients with mitochondrial myopathy even in the absence of LSM. Muscle levels of TC and FC were lower in patients with respiratory chain defects than in those with normal respiratory chain (P < 0.01). In contrast, LCAC levels were significantly increased (P < 0.05). Carnitine levels did not differ significantly, among patients with different respiratory-chain defects. Consequently, these patients, owing to their biochemical block, reduce progressively the muscle carnitine pool and subsequent LCAC rise, due to long-chain fatty acid (LCFA) accumulation. PMID- 8505936 TI - The electrodiagnosis of carpal tunnel syndrome. PMID- 8505935 TI - Arterial hypertension, nifedipine, and myasthenia gravis. PMID- 8505937 TI - F-latency in acute poliomyelitis. PMID- 8505938 TI - Effect of thermode temperature on thermal testing. PMID- 8505939 TI - Turn/amplitude-analysis and standardized muscular fatigue in neuromuscular disorders. PMID- 8505940 TI - Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. AB - BACKGROUND: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice. METHODS: We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed. RESULTS: Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001). CONCLUSIONS: These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors. PMID- 8505941 TI - Brief report: lymphoma of donor origin occurring in the porta hepatis of a transplanted liver. PMID- 8505942 TI - Malaria chemoprophylaxis for the traveler. PMID- 8505943 TI - Clinical problem-solving. One more hypothesis. PMID- 8505944 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 26-1993. A 73-year-old man with an enlarging inguinal mass 10 years after treatment for prostate and colon cancers. PMID- 8505945 TI - Diagnosis in the public domain. PMID- 8505946 TI - Digoxin in heart failure. PMID- 8505947 TI - Cat scratch disease. From feline affection to human infection. PMID- 8505948 TI - The early treatment of acute biliary pancreatitis. PMID- 8505949 TI - The early treatment of acute biliary pancreatitis. PMID- 8505950 TI - The early treatment of acute biliary pancreatitis. PMID- 8505951 TI - The early treatment of acute biliary pancreatitis. PMID- 8505953 TI - Early detection of HIV in neonates. PMID- 8505952 TI - Menetrier's disease and Helicobacter pylori. PMID- 8505954 TI - Early detection of HIV in neonates. PMID- 8505955 TI - Mooren's corneal ulcers and hepatitis C virus infection. PMID- 8505956 TI - Plasma endothelin and the hepatorenal syndrome. PMID- 8505957 TI - Plasma endothelin and the hepatorenal syndrome. PMID- 8505958 TI - A population-based study of dementia in 85-year-olds. PMID- 8505959 TI - A population-based study of dementia in 85-year-olds. PMID- 8505960 TI - Drowning. PMID- 8505961 TI - Drowning. PMID- 8505962 TI - Drowning. PMID- 8505964 TI - Microbes ever marching. PMID- 8505963 TI - Cat scratch disease in Connecticut. Epidemiology, risk factors, and evaluation of a new diagnostic test. AB - BACKGROUND: Although cat scratch disease is commonly diagnosed in patients who have unexplained regional lymphadenopathy after encounters with cats, its epidemiology and the risk factors for disease are not clearly defined, and there is no generally accepted diagnostic test. METHODS: We conducted a physician survey to identify cases of cat scratch disease occurring over a 13-month period in cat owners in Connecticut. We interviewed both the patients (or their parents) and controls matched for age who owned cats. Serum from the patients was tested for antibodies to Rochalimaea henselae with a new, indirect fluorescent-antibody test. RESULTS: We identified 60 patients with cat scratch disease and 56 age matched subjects. Patients were more likely than controls to have at least one pet kitten 12 months old or younger (odds ratio, 15), to have been scratched or bitten by a kitten (odds ratio, 27), and to have had at least one kitten with fleas (odds ratio, 29). A conditional logistic-regression analysis found that in kitten-owning households, patients were more likely than controls to have been scratched or bitten by a cat or kitten (odds ratio, 12.4; 95 percent confidence interval, 1.0 to 150). Of 45 patients, 38 had serum samples with titers of 1:64 or higher for antibody to R. henselae, as compared with 4 of 112 samples from controls (P < 0.001). The positive predictive value of the serologic test was 91 percent. Of 48 serum samples from patients' cats, 39 were positive for antibodies to R. henselae, as compared with positive samples from 11 of 29 control cats (P < 0.001). CONCLUSIONS: Cat scratch disease is strongly associated with owning a kitten, and fleas may be involved in its transmission. The serologic test for rochalimaea may be useful diagnostically, and our results suggest an etiologic role for this genus. PMID- 8505965 TI - Germany wants to modify gene laws. PMID- 8505966 TI - Germany debates proper niche for blue-list institutes. PMID- 8505967 TI - Internal fight threatens future of Strangeways laboratory in Britain. PMID- 8505968 TI - Biology in China suffers from government neglect. PMID- 8505969 TI - Canadian drug companies fund universities. PMID- 8505970 TI - Unique fund targets quality. PMID- 8505971 TI - Biotechnology looks for niche that will profit local science. PMID- 8505972 TI - Molecular deconstructivism. PMID- 8505973 TI - Social status and sex. PMID- 8505974 TI - Contaminated blood case nears end. PMID- 8505975 TI - Cancer. A gene for neurofibromatosis 2. PMID- 8505976 TI - Cell physiology. Secretion without full fusion. PMID- 8505977 TI - Nucleic acid architecture. Tetrads through interdigitation. PMID- 8505978 TI - Amplification and sequencing of DNA from a 120-135-million-year-old weevil. AB - DNA has been successfully isolated from both fossilized plant and animal tissues. The oldest material, dated as 25-40 million years old (Tertiary), was obtained from amber-entombed bees and termites. Tissues from both these insects yielded DNA of good quality, which could be amplified by the polymerase chain reaction (PCR) and subsequently sequenced, including the genes encoding 18S ribosomal RNA and 16S rRNA. We report here the extraction of DNA from a 120-135-million-year old weevil (Nemonychidae, Coleoptera) found in Lebanese amber, PCR amplification of segments of the 18S rRNA gene and the internal transcribed spacer, and the corresponding nucleotide sequences of their 315- and 226-base-pair fragments, respectively. These sequences were used for preliminary phylogenetic analysis of the nemonychid's sequence with three extant coleopterans: Lecontellus pinicola (Nemonychidae), Hypera brunneipennis (Curculionidae) and the mealworm Tenebrio molitor (Tenebrionidae), and two extant dipterans: the fruitfly Drosophila melanogaster (Drosophilidae) and mosquito Aedes albopictus (Culicidae) for the purpose of ascertaining the origin of the extracted and amplified DNA. The results revealed that the PCR-amplified material is that of the extinct nemonychid weevil. This represents the oldest fossil DNA ever extracted and sequenced, extending by 80 million years the age of any previously reported DNA. PMID- 8505979 TI - Honest signalling among gametes. AB - The gametes of many lower eukaryotic organisms emit pheromones that attract gametes of the opposite mating type or sex. Gametes move or grow in the direction of the highest pheromone concentration, suggesting that the strength of the pheromonal signal is used to infer proximity, or that the strongest signal is most likely to be notice. Here I offer a new explanation of pheromonal signalling and chemotaxis in gametes. I show that pheromonal signals can be interpreted as sexually selected traits that honestly advertise variation in quality among gametes, given that signals are costly to produce and that gametes compete; by 'quality' I refer to some aspect of a gamete's fitness. A gamete's preference for a mating partner, then, is predicted to vary with the quality of a prospective partner as inferred from the strength of its signal. This view can explain characteristics of the signalling and mate selection behaviours of gametes that are not predicted by models of mate choice based on proximity or 'passive attraction' to the strongest signal. These include repeated partner exchanges, escalated exchanges of mating pheromones, and rejection of gametes that signal at low levels. PMID- 8505980 TI - Contour from motion processing occurs in primary visual cortex. AB - Relative motion is one of the most salient cues for segmentation of a visual scene into separate objects. This is illustrated by the vivid contours that are perceived when random dot patterns move in different directions. Once motion is halted in such displays the segmentation contours disappear. This makes random dot patterns ideal for the study of contour from motion processing in isolation. Contour from motion processing obviously relies on direction-selective neurons, which are found in many visual cortical areas. It is, however, largely unknown at what level of processing their signals interact to serve the global process of motion-based image segmentation. To answer this question, we recorded visually evoked potentials, both in man and in awake monkey, to a stimulus specifically designed to signal the presence of neuronal activity related to contour from motion processing. We report here that response components specific to contour from motion were elicited only when the stimulus yielded a contour percept. In awake monkey, the sources of these components were located within the supra- and infra-granular layers of primary visual cortex. We conclude that V1 is involved in image segmentation processing. PMID- 8505982 TI - The Nagel anomaloscope and seasonal variation of colour vision. AB - In 1948 the German physicist, Manfred Richter, reported that colour vision has a seasonal variation. For four colour-normal subjects, he found a sinusoidal variation in the proportion of red and green required to match a monochromatic yellow, the equation known as the 'Rayleigh match'. In summer, subjects required more red in their mixture. The measurements were made with the Nagel anomaloscope, an instrument introduced in 1907 and which today, essentially unchanged, remains the definitive clinical instrument for classifying the many phenotypic variations in colour vision. The variation that Richter recorded in the red-green ratio was large (three Nagel units), and it now takes on fresh interest because it is comparable in size to the difference in Nagel settings later reported between normal observers of different genetic types. We have been able to replicate Richter's result, but report here that it is almost certainly instrumental: the Nagel anomaloscope proves to be very sensitive to ambient temperature. PMID- 8505981 TI - Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. AB - In humans, trauma to a peripheral nerve may be followed by chronic pain syndromes which are only relieved by blockade of the effects of sympathetic impulse traffic. It is presumed that, after the lesion, noradrenaline released by activity of sympathetic postganglionic axons excites primary afferent neurons by activating alpha-adrenoceptors, generating signals that enter the 'pain pathways' of the central nervous system. The site of coupling is unclear. In some patients local anaesthesia of the relevant peripheral nerve does not alleviate pain, implying that ectopic impulses arise either within the central nervous system, or in proximal parts of the primary afferent neurons. In experimentally lesioned rats, activity can originate within the dorsal root ganglia. Here we report that, after sciatic nerve ligation, noradrenergic perivascular axons in rats sprout into dorsal root ganglia and form basket-like structures around large-diameter axotomized sensory neurons; sympathetic stimulation can activate such neurons repetitively. These unusual connections provide a possible origin for abnormal discharge following peripheral nerve damage. Further, in contrast to the sprouting of intact nerve terminals into nearby denervated effector tissues in skin, muscle, sympathetic ganglia and sweat glands, the axons sprout into a target which has not been partially denervated. PMID- 8505983 TI - Intercellular signalling in Drosophila segment formation reconstructed in vitro. AB - Genetic studies show that intercellular signalling is involved in key steps in Drosophila melanogaster development, but it has not previously been possible to investigate these processes in simplified in vitro systems. Analysis of engrailed (en) and wingless (wg) and other segment polarity genes suggests that two or more intercellular signalling processes may be involved in intrasegmental patterning. Expression of en and wg begins about three hours after egg laying, in adjacent rows of cells in the posterior half of each segmental primordium. In wg- embryos and in conditional mutants in which wg function is inactivated during a critical period between three and five hours after egg laying, early en expression begins normally but then disappears within several hours. The wg gene encodes a protein highly similar to the product of the mouse Wnt-1 proto-oncogene, a secreted glycoprotein; wg protein is proposed to function as an extracellular signal, maintaining en expression and activating other molecular and morphogenetic processes in nearby cells. Several lines of evidence support the model, including the secretion of wg protein in the embryo, genetic mosaic experiments and cell lineage studies. We tested this model using purified embryonic cells isolated by whole animal cell sorting, and validated three key predictions: (1) when en expressing cells from early embryos are grown alone in culture, they rapidly and selectively lose en expression; (2) purified wg-expressing cells provide a locally active signal that prevents this loss; (3) heterologous cells engineered to express wg also show signalling activity, indicating that wg protein alone, or in conjunction with more generally expressed factors, is the signal. PMID- 8505984 TI - Release of secretory products during transient vesicle fusion. AB - Patch-Camp experiments have shown that fusion of secretory granules with the plasma membrane does not always occur as an all-or-none event, but can develop slowly in a fluctuating manner or can be transient. These observations suggested that release could be detected during such incomplete fusion events. To test this hypothesis we have combined patch-clamp measurements of the activity of single exocytotic fusion pores in beige mouse mast cells with the electrochemical detection of serotonin released during the exocytotic events. We report here that on fusion pore opening there is a small release of serotonin which is directly proportional to the pore conductance. We also show that a significant release occurs during transient fusion events. These results demonstrate, to our knowledge for the first time, release of a neurotransmitter from a secretory vesicle that did not undergo complete fusion. PMID- 8505985 TI - Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. AB - Spontaneous errors in DNA replication have been suggested to play a significant role in neoplastic transformation and to explain the chromosomal alterations seen in cancer cells. A defective replication factor could increase the mutation rate in clonal variants arising during tumour progression, but despite intensive efforts, increases in tumour cell mutation rates have not been unambiguously shown. Here we use an unbiased genomic fingerprinting technique to show that 12 per cent of colorectal carcinomas carry somatic deletions in poly(dA.dT) sequences and other simple repeats. We estimate that cells from these tumours can carry more than 100,000 such mutations. Only tumours with affected poly(dA.dT) sequences carry mutations in the other simple repeats examined, and such mutations can be found in all neoplastic regions of multiple tumours from the same patient, including adenomas. Tumours with these mutations show distinctive genotypic and phenotypic features. We conclude that these mutations reflect a previously undescribed form of carcinogenesis in the colon (predisposition to which may be inherited) mediated by a mutation in a DNA replication factor resulting in reduced fidelity for replication or repair (a 'mutator mutation'). PMID- 8505986 TI - [Relationship between socioeconomic status and differences in health care utilization in pregnancy, delivery and puerperium]. AB - OBJECTIVE: Description of differences in pre-, peri- and postnatal care, according to socio-economic status (SES). SETTING: Geographically defined areas of 21 child health clinics (CHC) in several parts of the Netherlands. DESIGN: Retrospective cohort study. MATERIALS AND METHOD: Of all women who delivered a live-born child in the period April 1988-October 1989 and who were residents of the districts of the CHCs (n = 2119), data were recorded during the home visit post partum by the district nurses. Complete data were available of 2060 (97.2%) mothers. The care provided was defined as prenatal care and attendance at delivery (midwife, general practitioner, obstetrician and combinations), place and mode of delivery, and place of lying-in period. The indicator for SES was the educational level of the mother. In multivariate analyses, age, parity, degree of urbanisation of residential area, distance between home and hospital, ethnicity, height, smoking, health problems during pregnancy, obstetrical history, preterm birth and low birth weight were included in order to correct for possible confounding effects of these factors. RESULTS: Compared to the higher SES group, there was an increased risk in the lower SES group for a delivery in hospital (OR 1.60; 95% CI 1.16-2.20); the probability of having a complete lying-in period at home decreased according to the SES level (low SES: OR 0.47; 95% CI 0.34-0.65). Differences in mode of delivery (notably caesarean section) were very small and not significant. CONCLUSIONS: In the Netherlands there are socio-economic differences in perinatal care and the place of the lying-in period. Women of higher SES delivered more often at home and more often had their lying-in period at home, irrespective of other factors. Preferences of the mothers with respect to place of confinement were not taken into account in this study. PMID- 8505987 TI - [Postanginal sepsis caused by Fusobacterium necrophorum: Lemierre syndrome]. AB - Postanginal sepsis or Lemierre's syndrome is characterised by septic thrombophlebitis of the jugular vein, metastatic abscesses in the lungs, soft tissues, joints or elsewhere, occurring several days to two weeks after tonsillitis or pharyngitis. The primary pathogen is a Gram-negative anaerobic rod, mostly Fusobacterium necrophorum. Previously healthy, young adults are affected mainly and the syndrome was seen more frequently in the pre-antibiotic era than it is nowadays. In the three young patients described here, a girl aged 15 and two boys aged 18 and 16, F. necrophorum was isolated from blood or pus. Histories and examinations were suggestive of Lemierre's syndrome. Ultrasound and CT scanning of the neck and other localisations proved to be important diagnostic tools in assessing the diagnosis. Response to therapy was slow and depended in at least one case on adequate drainage of abscesses. If the syndrome is suspected, initial antibiotic treatment should provide adequate coverage of anaerobic bacteria. In previously healthy patients with chills and fever occurring several days after a sore throat, Lemierre's syndrome should be considered. PMID- 8505988 TI - [Erroneous diagnosis of lithium poisoning due to use of lithium-heparin bloodletting tubes]. AB - In two male patients, aged 53 and 21 years, lithium intoxication was suspected. The diagnosis was apparently confirmed by blood testing (the lithium concentrations amounted to 3.68 and 1.82 mmol/l, respectively). Retrospectively however it was found that blood sampling tubes with lithium-heparin as the anticoagulant had been used. No lithium intoxication was present in the patients. Clear instructions in writing are necessary to prevent this error. PMID- 8505989 TI - [Lumbar spinal stenosis]. PMID- 8505990 TI - [Lumbar spinal stenosis]. PMID- 8505991 TI - [Multiresistant tuberculosis]. PMID- 8505992 TI - [Oral rehydration therapy in Europe]. PMID- 8505993 TI - [Neck cyst or metastasis? Appearances are deceptive]. PMID- 8505994 TI - [Attacks of unconsciousness]. PMID- 8505995 TI - [Vasovagal reaction]. PMID- 8505996 TI - [Indications for brain biopsy in the diagnosis of intracerebral lesions in patients with AIDS]. PMID- 8505997 TI - [Errors and uncertainties in clinical practice; the obstetrician's viewpoint]. PMID- 8505998 TI - [Are psychopharmaceutical agents prescribed too often in nursing homes?]. PMID- 8505999 TI - [Schizophrenia: unity in diversity]. PMID- 8506000 TI - [Korsakoff syndrome]. PMID- 8506001 TI - [Reduction of drug intake following admission to a psychogeriatric nursing home: discontinuation is possible]. AB - OBJECTIVE: To describe the changes in de first six weeks after admission and to consider the factors which influence drug intake. PLACE: Psychogeriatric nursing home facility Joachim en Anna in Nijmegen, the Netherlands. DESIGN: Retrospective analysis of medical charts. PATIENTS AND METHODS: Of 356 patients drug intake on the day of admission and six weeks after were registered as well as diagnosis on dementia, domicile before admission, degree of dependence and comorbidity. Medication was divided into sixteen groups. Changes in drug taking were tested by means of the Wilcoxon test. The influence of the factors mentioned was analysed by an analysis of variance and the logistic regression procedure. RESULTS: The mean number of drugs taken per patient decreased from 2.5 at admission to 2.1 at six weeks. In particular psychotropics, diuretics, cardiac drugs and drugs grouped as a 'miscellaneous' were reduced. Domicile before admission, diagnosis of dementia, comorbidity and less significantly the degree of dependence all had an influence on drug intake. Patients admitted from old people's homes or a general hospital had twice as much medication as patients who lived in their own homes. Main differences were seen in the use of psychotropics and diuretics. Patients suffering from Alzheimer's disease used fewer drugs than patients with a multi-infarct dementia. The latter had a higher intake of diuretics, cardiac drugs and laxatives, while Alzheimer patients used more psychotropics. Patients with the highest degree of dependence used more laxatives and fewer psychotropics or diuretics. CONCLUSION: Reduction of drug intake after admission to a psychogeriatric nursing home is possible. Several factors influence drug intake. These should be considered when comparing different studies. PMID- 8506002 TI - [Psychiatric disorders in patients of a memory outpatient clinic]. AB - OBJECTIVE: To determine whether psychiatric conditions other than depression are relevant in elder patients with memory disturbances. METHODS: 430 consecutive outpatients (242 males, 188 females; mean age 61.7 years) who visited the Maastricht Memory Clinic were examined, according to a standardised diagnostic procedure, including somatic, neurological, psychiatric and neuropsychological examination. Psychiatric disorders were diagnosed according to DSM-III(-R) criteria. RESULTS: Of 152 patients with dementia, 34 had a secondary depressive syndrome, 19 another secondary psychiatric disorder. Of the 37 patients with a psycho-organic disorder other than dementia, 16 had an organic mood disorder. Of the other 241 patients, 152 had 159 primary psychiatric diagnoses: mood disorders in 100 cases and other psychiatric disorders in 59 cases, especially adjustment disorders, anxiety disorders and personality disorders. Together, only 60% percent of all primary or secondary psychiatric disorders were mood disorders. Various ways in which organic substrate, cognitive problems and psychopathology can be interrelated are discussed. CONCLUSION: Although affective disorders were the most frequent psychiatric disorders, several other psychiatric conditions were related to memory disturbances as well. Psychiatric assessment in patients with memory complaints should not be restricted to the diagnosis of depressive symptoms. PMID- 8506003 TI - [Disabling constipation following Wertheim's radical hysterectomy]. AB - The prognosis of patients after a radical hysterectomy according to Wertheim because of a carcinoma of the cervix is good, yet the long-term morbidity is considerable. In a retrospective investigation regarding constipation, a questionnaire was sent to 48 patients who had undergone hysterectomy in the period 1975-1990 in the Ikazia Hospital, Rotterdam. The response rate was 83%. Of the 40 respondents, 18% acquired constipation after the operation (< 3 times defaecation per week), and 33% needed prolonged straining; 13% had abdominal cramps, 20% had started to use laxatives, 48% had an increased consistency of the faeces, and 40% had to assist defaecation with the fingers. The incidence of chronic constipation after radical hysterectomy according to Wertheim is more than 20%; this kind of morbidity is insufficiently recognised. Operative treatment of these constipated patients can be successful. PMID- 8506004 TI - [Endometrial carcinoma during estrogen replacement therapy in spite of addition of progestagens]. PMID- 8506005 TI - [Constipation in children]. PMID- 8506006 TI - [Informed consent communication for organ donation]. PMID- 8506007 TI - [Combination external and internal radiotherapy for esophageal carcinoma: current perspectives]. PMID- 8506009 TI - [Long-term results of continuous subcutaneous apomorphine pump therapy in patients with advanced Parkinson disease]. PMID- 8506008 TI - [Parkinson disease--a mitochondrial myopathy?]. PMID- 8506010 TI - [The diagnostic value of nuclear magnetic resonance tomography, multimodal evoked potentials and cerebrospinal fluid examination in multiple sclerosis]. AB - Seventy patients with multiple sclerosis (according to Poser's criteria) were clinically assessed and examined with MRI, multimodal evoked potentials (VEP, AEP, SSEP) and CSF analysis (transformed lymphocytes, IgG-Index, oligoclonal banding). In relation to the clinical criteria of McAlpine 40 patients had possible, 16 patients probable and 14 patients definite MS. 81% of the patients (73% possible MS, 94% probable MS, 93% definite MS) had multiple white matter lesions detected by MRI, 79% (78% possible MS, 94% probable MS, 64% definite MS) had an abnormal CSF profile and 67% (60% possible MS, 75% probable MS, 79% definite MS) abnormal results in multimodal EP testing. Of the patients who experienced only one attack (n = 40) 78% had multiple lesions on MRI, 88% had abnormal CSF-findings and 60% had pathologic EPs. Patients with two or more attacks showed in 87% multiple lesions on MRI, in 77% abnormal EPs and in 70% abnormal CSF findings. The number of abnormal MRI and EPs increases with the duration of the disease. 13 patients with a normal MRI were discussed separately. MRI is the most sensitive method in detecting the spatial pattern of disseminated lesions. To monitor the dissemination over time a careful clinical follow-up is still mandatory. PMID- 8506011 TI - [Results of 100 consecutively operated patients with acoustic neuroma]. AB - The results from 100 patients with 103 acoustic neurinomas who were operated on between February 1979 and April 1992 are presented. All patients were placed in the half-sitting position and operated on by the same surgeon using the suboccipital-trans-meatal approach. Postoperative facial nerve function was good in 56%, moderate in 20% and poor in 24% of our patients. Preservation of useful hearing was achieved in 21%: the smaller the tumor, the better the functional result. However, the early symptoms of acoustic neuromas (tinnitus, dizziness, feeling of unsteadiness) were only slightly improved by the operation. The result concerning tinnitus seemed to be better after sacrificing the cochlear nerve. The number of patients with ataxia increased postoperatively, although objective ataxia decreased. Dizziness improved regardless of the tumor size. PMID- 8506012 TI - [Post-polio syndrome]. AB - The post-polio syndrome is a late sequel of former poliomyelitis. Patients develop slowly progressive weakness, fatigue and pain. We report 13 cases. PMID- 8506013 TI - [Mononeuritis multiplex as initial manifestation of systemic granulomatosis]. AB - We report two young patients with a painful and rapidly progressive polyneuropathy of the mononeuritis multiplex type confiding them to bed. Extensive investigations led to the diagnosis of a granulomatosis in both: Churg Strauss allergic granulomatosis in one and Wegener's granulomatosis in the other. The importance and frequency of peripheral nervous system manifestations in the presenting clinical pattern of a systemic granulomatosis and vasculitis are discussed. Their proper recognition with regard to available effective therapeutic measures is stressed. PMID- 8506014 TI - [POEMS syndrome: a contribution to differential diagnosis of polyneuropathy]. AB - The POEMS syndrome is a synopsis of different symptoms such as polyneuropathy, organomegaly, endocrine disturbances, M-protein and skin changes. The leading symptoms are neuropathy and the skin symptoms. Additionally, a monoclonal light chain gammopathy is often found. The administration of immunosuppressive drugs yields a substantial improvement in some cases. We report here about a 72 year old lady who fell ill with a rapidly progressive neuropathy accompanied by hyperpigmentation and a morphea-like induration of the skin. A biopsy of the sural nerve showed a demyelinating axonal neuropathy and a focal vasculitis. Isoelectric focussing revealed oligoclonal bands in cerebrospinal fluid and serum. The cortisol serum level was very low and there were signs of a latent diabetes mellitus. These clinical features correspond to the POEMS syndrome. The prescription of initially 1 mg and later 0.5 mg prednisone improved the patient's condition dramatically. PMID- 8506015 TI - [Membranous lipodystrophy (Nasu-Hakola disease)]. AB - We present a case-report and review of the literature on membranous lipodystrophy. This is a rare disease characterized by progressive presenile dementia, multiple bone cysts with pathologic fractures, generalized cerebral seizures with abnormal EEG and bilateral calcifications of the basal ganglia. Neuropathological findings are neuroaxonal dystrophy with neurofilaments in the axons, neuronal cell loss and fibrillary gliosis. The disease is usually inherited as an autosomal recessive. The pathogenesis is unknown but is believed to be an enzyme defect of the glycolipid metabolism. PMID- 8506016 TI - [Unmasking congenital myotonia by hypothyroidism]. AB - A case with the combination of hypothyroidism and true myotonia is reported, in which the latter first became manifest clinically together with the thyroid disorder and improved with L-thyroxine therapy. The hypothyroidism itself caused very few symptoms, and the diagnosis was not made until examination for myotonia. The effect of each disorder on muscle function seems to be additive. PMID- 8506017 TI - [Folic acid deficiency in patients hospitalized with depression? A pilot study of clinical relevance]. AB - Seventy-seven depressive inpatients were studied in a pilot study to determine their serum and red cell folate levels at admission. Only one depressive inpatient with a low serum folate value had a history of an illness-related lack of nutrition prior to admission, and the low value was only on day 1 of the study. Our results demonstrate that folate acid deficiency is not as common in depressive inpatients as reported, especially in British studies for two reasons: different eating habits and a methodological problem. PMID- 8506018 TI - [Myasthenia gravis in AIDS and neurosyphilis]. AB - The co-occurrence of myasthenia gravis and AIDS in a 38 year old drug addict with HIV-infection is reported. The diagnosis "myasthenia gravis" is based on clinical features with muscle weakness worsening with exercise and depending on the time of day, and secondly on the result of electrophysiological tests, with a typical decrement in repetitive nerve conduction study, and on the presence of antibodies to acetylcholine receptors. A co-existing neurosyphilis was treated intravenously with penicillin G, resulting in good improvement of the associated myopathy. The remaining muscle weakness responded well to treatment with pyridostigmine bromide started after the end of the antibiotic therapy. A tumor in the anterior mediastinum measuring 3 by 2 cm was diagnosed by CT scan and removed, histology showed normal thymus tissue. After operation the patient became asymptomatic on treatment with low dosage pyridostigmine (3 x 30 mg). The association of myasthenia gravis with AIDS may derive from an alteration of the immune system based on changes in the thymus gland. Differential diagnosis in AIDS patients with generalized weakness should include a myasthenic reaction. PMID- 8506019 TI - [Acute transverse myelitis after rubella infection in an adult]. PMID- 8506020 TI - [Tuberculous radiculomyelitis--good response to therapy only in early detection]. AB - This is a report of a case of radioculomyelitis secondary to tuberculous meningitis. The importance of an early diagnosis is stressed in the light of reports on good outcome after prompt commencement of therapy. Polymerase chain reaction is now available for quick confirmation of the suspected diagnosis. PMID- 8506021 TI - Localization of somatostatin receptors in subcortical visual centres of the rat during development. Effect of neonatal enucleation on the expression of somatostatin receptors. AB - Previous studies have shown that both somatostatin and somatostatin receptors are expressed in the visual system of the rat early during ontogenesis, suggesting that somatostatin plays a role in the development of visual functions. In the present study, we have examined the localization of somatostatin receptors in the lateral geniculate nucleus and the superior colliculus of the developing rat by autoradiography, and we have investigated the effect of neonatal enucleation on the density of receptors in young and adult animals. In the dorsal part of the lateral geniculate nucleus, somatostatin receptors were transiently expressed during the first two postnatal weeks, while in the ventral part, receptors were detected during the whole developmental period. In the superior colliculus, a high density of somatostatin receptors was measured before eye opening; thereafter the concentration of receptors decreased markedly in the whole structure to reach the adult level. Uni- or bilateral enucleation one day after birth only induced minor modifications of the expression of somatostatin receptors in the lateral geniculate nucleus and colliculus. Conversely, bilateral enucleation caused a significant reduction of the density of receptors in the inter-geniculate leaflet and the medial zone of the ventral lateral geniculate nucleus. Taken together, these results indicate that, in the relay nuclei, somatostatin receptors are not borne by retinal afferents. The presence of high densities of receptors in the lateral geniculate nucleus and superior colliculus during development suggests that somatostatin exerts trophic activities in these structures. In adult rat, somatostatin is probably involved in the modulation of visual information in the superior colliculus, but not in the dorsal lateral geniculate nucleus. PMID- 8506022 TI - Annual variations in the vasopressin neuron population of the human suprachiasmatic nucleus. AB - The mammalian suprachiasmatic nucleus is considered to be the major component of the biological clock, involved in the temporal organization of a wide variety of physiological and behavioral processes. The present study was conducted to investigate whether there are diurnal or annual variations in the morphology of the vasopressin-containing neuron population of the suprachiasmatic nucleus in human beings. To that end, the brains of 48 human subjects were investigated. A marked annual variation was observed in the volume and vasopressin cell number of the human suprachiasmatic nucleus: the volume of the vasopressin cell population was, on average, 2.5 times larger in October-November than in May-June and contained 2.7 times as many vasopressin-immunoreactive neurons. In general, the annual cycle of the human suprachiasmatic nucleus showed a non-sinusoidal pattern with a maximum in early autumn, a lower plateau in winter and a deep trough in late spring and early summer. In contrast, no such seasonal variations could be detected in suprachiasmatic nucleus vasopressin numerical cell density or cell nuclear diameter. The number of vasopressin-immunoreactive neurons in the paraventricular nucleus of the hypothalamus, on the other hand, did not show any significant periodic changes over the year, indicating the specificity of the suprachiasmatic nucleus rhythm. In contrast with the annual cycle of the suprachiasmatic nucleus, no significant diurnal variations were observed in any of these parameters. In conclusion, the findings indicate that photoperiod may be considered a potential environmental factor controlling the activity of the vasopressin system of the human suprachiasmatic nucleus. PMID- 8506023 TI - Exogenously administered alpha-bungarotoxin binds to embryonic chick spinal cord: implications for the toxin-induced arrest of naturally occurring motoneuron death. AB - Administration of alpha-bungarotoxin and other curare-like drugs during embryogenesis arrests motoneuron death which normally occurs in the spinal cord from day 6 to day 10 of embryogenesis. The accepted explanation is that such motoneuron rescue is mediated by inhibition of neuromuscular transmission following the blockade of nicotinic cholinoceptors at the neuromuscular junction. In this study we investigated a further possibility, namely that motoneuron rescue might also involve the blockade of alpha-bungarotoxin-sensitive sites within the spinal cord. The kinetic profile of [125I]alpha-bungarotoxin binding was examined in the brachial and lumbar regions of chick spinal cord at embryonic day 15. Binding was specific and apparently saturable within the range 1-34 nM reaching a maximum after 45 min. Specific binding involved a single class of non interacting sites with a KD of 8.0 nM and a Bmax of 106 +/- 12 fmol/mg of protein. Nicotine displaced specific [125I]alpha-bungarotoxin binding in a concentration-dependent manner. Furthermore, specific binding dissociated slowly in the absence of nicotine. Autoradiographs localizing [125I]alpha-bungarotoxin binding in embryonic spinal cord revealed that, at embryonic day 15, specific toxin binding sites could be detected throughout the gray matter. In contrast, at embryonic day 6, the ventral horn contained the majority of specific binding sites. Exogenously administered [125I]alpha-bungarotoxin reached and bound to nicotine-sensitive sites in the spinal cord at embryonic day 7. To conclude, these data demonstrate that central nicotine-sensitive sites which bind [125I]alpha-bungarotoxin in a saturable and specific manner were present at the beginning of the critical motoneuron death phase of neurogenesis and that they were accessible to exogenously administered toxin. It is proposed that the [125I]alpha-bungarotoxin binding characterized here is to a class of putative alpha-bungarotoxin-sensitive nicotinic cholinoceptors. These studies raise the possibility that alpha-bungarotoxin blockade of such putative nicotinic cholinoceptors within the spinal cord may contribute to toxin-induced arrest of naturally occurring motoneuron death. PMID- 8506024 TI - Neuronal death and neurotrophin gene expression: long-lasting stimulation of neurotrophin-3 messenger RNA in the degenerating CA1 and CA4 pyramidal cell layers. AB - Neurotrophin-3 has been characterized as the product of a gene cloned by homology with nerve growth factor and brain-derived neurotrophic factor. Recombinant neurotrophin-3, like nerve growth factor and brain-derived neurotrophic factor, has been shown to enhance survival and differentiation of specific neuronal populations in vitro. However, little is known about its function and regulation in vivo. Both brain-derived neurotrophic factor and nerve growth factor messenger RNAs increased in adult rat brain, in a wide range of excitatory paradigms. In contrast, neurotrophin-3 messenger RNA decreased in some of them. Neurotrophin-3 is the most highly expressed neutrophic factor in immature areas of the central nervous system. However, no stimulation of its expression in the mature central nervous system, either in physiological or pathological conditions, has been described to date. This behaviour suggests that neurotrophin-3 could be involved in biological roles different from the prototypes nerve growth factor and brain derived neurotrophic factor. Excitatory amino acid receptor-mediated neurotoxicity (excitotoxicity) is believed to contribute to neuronal loss in a wide range of neurodegenerative conditions (for a review, see Ref. 17). Moreover, locally increased levels of the endogenous excitotoxin quinolinic acid may be involved in the natural development of neurodegenerative diseases. The unilateral intrahippocampal injection of 120 nmol of quinolinic acid induced seizures together with local neurodegeneration in specific cell layers. In situ hybridization histochemistry was used to analyse the spatiotemporal pattern of expression of neurotrophin-3. As in other excitotoxic paradigms, neurotrophin-3 messenger RNA clearly decreased, nearly disappearing, in the contralateral hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506025 TI - Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures. AB - We have examined the effects of pentylenetetrazol-induced epileptic seizures on brain-derived neurotrophic factor messenger RNA and protein and on the messenger RNA of its receptor in the rat. Pentylenetrazol, which acts at the picrotoxin recognition site of the GABAA receptor, was injected intraperitoneally and induced seizures by decreasing the inhibitory GABAergic activity. The effects of a single acute convulsive dose (50 mg/kg) of pentylenetetrazol were analysed at different time points by in situ hybridization or immunohistochemistry. Kindling was induced by daily subconvulsive injections (30 mg/kg) of pentylenetetrazol. At different time points during the kindling process, the messenger RNAs of brain derived neurotrophic factor and trkB and the protein levels of brain-derived neurotrophic factor were analysed. We showed that brain-derived neurotrophic factor messenger RNA dramatically increased in neurons of the granule cell layer, piriform cortex and amygdala 3 h but not 6 h after an acute high dose of pentylenetetrazol, while brain-derived neurotrophic factor-like immunoreactivity was decreased in the granule cell layer and neurons of the hilus. The trkB messenger RNA was similarly increased 3 h and 6 h after the injection and returned to control levels after 24 h. The first change during the kindling development was seen after the first severe seizure: brain-derived neurotrophic factor messenger RNA was markedly increased in the piriform cortex and amygdala but not in the hippocampus. In fully kindled rats, which had several severe seizures, brain-derived neurotrophic factor messenger RNA and trkB messenger RNA were unaffected 3 h and 24 h after the last pentylenetetrazol injection. However, brain-derived neurotrophic factor-like immunoreactivity was markedly increased in the hippocampal formation 3 h, 24 h and three days after the last pentylenetetrazol injection, and still increased after 10 days. These results suggest that brain-derived neurotrophic factor may be involved in protection mechanisms after damage during seizures and in sprouting responses. The piriform cortex/amygdala seems to be an area of origin for the kindling development. PMID- 8506026 TI - The S-100 protein causes an increase of intracellular calcium and death of PC12 cells. AB - The S-100 protein-PC12 cell interaction has been studied as a model system of the possible physiological role played by S-100 protein in the nervous system. The data reported demonstrate that S-100 exerts a cytotoxic action which eventually leads to PC12 cell death, regardless of the cell cycle phase. The effect is specific for the S-100 isoforms, which are made up of two identical subunits and is abolished by a monoclonal antibody directed against the same isoforms. Other isoforms and/or calcium-binding proteins, such as troponin or calmodulin, do not induce the same effects. The action of S-100 on cell viability is not detectable in other cell lines of different embryological origin, such as 3T3, L1210, GH3. S 100 causes a rapid and considerable increase (two- to three-fold) of intracellular Ca2+ concentration in PC12 cells accompanied by cytostatic and cytotoxic action. It is postulated that this action also occurs in vivo, as part of the physiological action of this protein. PMID- 8506027 TI - Spatial heterogeneity of caffeine- and inositol 1,4,5-trisphosphate-induced Ca2+ transients in isolated snail neurons. AB - Inositol 1,4,5-trisphosphate- and caffeine-induced Ca2+ release was examined in neurons isolated from the mollusc Helix pomatia using Ca2+ indicator fura-2 and fluorescent digital-imaging microscopy technique. Extracellular application of caffeine caused a fast and pronounced augmentation of [Ca2+]i whose amplitude and kinetics differ in the centre of the cell and near its membrane. Mean values of caffeine-induced increase of [Ca2+]i were 0.97 +/- 0.11 microM at the periphery and 0.53 +/- 0.13 microM in the centre. The rates of rise and relaxation of caffeine-evoked [Ca2+]i transients were faster near the membrane. Pressure injection of inositol, 1,4,5-trisphosphate into the same neurons produced an abrupt and significant increase of [Ca2+]i in the centre (mean value of inositol 1,4,5-trisphosphate-induced elevation = 0.55 +/- 0.11 microM) while the response was smaller or even absent near the cellular membrane. Inositol 1,4,5 trisphosphate- and caffeine-induced Ca2+ transients did not affect each other. The data obtained indicate that in snail neurons these two calcium pools are not overlapping and at least some part of the caffeine-sensitive store is located close to the cellular membrane and that the inositol 1,4,5-trisphosphate sensitive one is located in the centre of the cell. PMID- 8506028 TI - Fast pre-potential generation in rat hippocampal CA1 pyramidal neurons. AB - Small all-or-none pre-potentials have been shown under some conditions to underlie antidromic and orthodromic spike discharge in somatic recordings of hippocampal pyramidal neurons [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. et al. (1961) J. Neurophysiol. 24, 225-242; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68; Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285]. These potentials are taken to reflect spike discharge in distant regions of the cell (axonal or dendritic) [Andersen P. and Lomo T. (1966) Expl Brain Res. 2, 247-260; Kandel E. R. and Spencer W. A. (1961) Ann. N. Y. Acad. Sci. 94, 570-603; Schwartzkroin P. A. (1977) Brain Res. 128, 53-68] or electronic spike conduction across a gap junction between neighboring pyramidal cells [Dudek F. E. et al. (1983) In Basic Mechanisms of Neural Hyperexcitability, pp. 31-73]. The present study compared pre-potentials recorded at the somatic and dendritic levels and used restricted applications of tetrodotoxin to examine the relationship between pre-potentials and Na+ spike discharge. Intrasomatic and intradendritic recordings were obtained from CA1 pyramidal neurons of rat hippocampal slices maintained in vitro. Orthodromic and antidromic spike discharge was evoked by stimulation of afferent fibers in stratum radiatum and pyramidal cell axons in the alveus, respectively. Focal pressure application of tetrodotoxin in the immediate vicinity of somatic or dendritic recordings uncovered pre-potentials following blockade of antidromic spike discharge. Blockade of these pre-potentials required the diffusion of tetrodotoxin to a location remote from the recording site. Focal application of tetrodotoxin in the cell body layer reliably uncovered orthodromic pre-potentials at the soma only when stimulus intensity was raised beyond threshold for somatic spike discharge; e.g. to intensities shown to initiate spike discharge in apical dendritic locations [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280]. These data provide evidence that propagation of a Na+ spike over the pyramidal cell axis is preceded by a depolarization in the form of a pre-potential. The uncovering of orthodromic somatic pre-potentials by tetrodotoxin during suprathreshold activation further supports the proposal [Spencer W. A. and Kandel E. R. (1961) J. Neurophysiol. 24, 272-285] that dendritic spike discharge [Turner R. W. et al. (1991) J. Neurosci. 11, 2270-2280] can underlie fast pre-potential generation in pyramidal cell somata. PMID- 8506029 TI - Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit--I. Spontaneous activity. AB - The background activity of hippocampal neurons was recorded extracellularly in waking rabbits in the control state and after systemic injections of physostigmine and scopolamine. Similar analysis was done in the hippocampus chronically deprived of ascending brainstem afferents. Cholinergic drugs control the number of hippocampal neurons with theta modulation and stability, but not the frequency of theta modulation. Increase of endogenous acetylcholine also resulted in regularization of the activity with suppression of delta modulation and complex spike discharges; its blockade produced the opposite changes. Both drugs changed the level of background activity in the majority of the neurons, but the overall mean frequency did not vary between the states. Regression analysis demonstrated significant negative correlations with dominating decrease in the level of discharges in high-frequency neurons (> 25 spikes/s) and its increase in low-frequency ones (< 25 spikes/s) after injection of both drugs. Stability of the overall mean frequency and uniformity of its shifts during both stimulation and suppression of the cholinergic component of theta-rhythm presumably indicate that the frequency of background activity, unlike its pattern, is not directly controlled by the cholinergic septal input. PMID- 8506030 TI - Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit- II. Septal input. AB - The aim of this paper was to evaluate the cholinergic component of the septohippocampal input signals in neuronal activity of the hippocampal fields CA1 and CA3 recorded extracellularly in chronic alert rabbits. Effects of electrical stimulation of the medial septal area were analysed in the control state, on the background of an increased level of endogenous acetylcholine (by physostigmine injection) and during its blockade by antimuscarinic drugs (scopolamine, atropine). Two groups of animals were used in the experiments: intact rabbits and rabbits with complete chronic undercutting of the septum, depriving the septohippocampal system of ascending medial forebrain bundle afferents. Primary inhibitory effects of standard duration (40-140 ms) evoked by medial septal area stimulation dominated in the hippocampus of intact rabbits (54%), though some neurons responded by initial diffuse excitation (37.5%); responses by single spike on-effects were observed in a minority of neurons (8.5%). The primary suppression of activity prevailed (90%) in animals with basal undercutting of the septum. In intact rabbits under physostigmine action, the effects of medial septal area stimulation were depressed or completely blocked in 78% of hippocampal neurons on the background of increased theta modulation of activity. Neuronal responses to medial septal area stimulation recovered at the background of muscarinic antagonists. These effects of cholinergic drugs were reproduced in animals without medial forebrain bundle. It is concluded that the initial effect of the septal input upon the hippocampal neurons consists of a general suppression of their activity (reset), depending upon a non-cholinergic (presumably GABAergic) component of the septohippocampal connections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506031 TI - Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit- III. Cortical input. AB - Cholinergic modulation of single cell responses and field potentials evoked in the hippocampus by electrical stimulation of the perforant path and mossy fibres was investigated in two groups of chronic unanesthetized rabbits--with intact hippocampus and with basally undercut septum (without ascending medial forebrain bundle afferents). In both groups of animals responses to stimulation were blocked or significantly depressed by i.v. physostigmine injection in many neurons (50% in the intact hippocampus and 69% in the hippocampus without medial forebrain bundle). In minor groups of neurons (10 and 8%, respectively), facilitation of responses was observed. Scopolamine restored initial responsiveness of hippocampal neurons and augmented effects of stimulation in some of them. The effect of physostigmine was reproduced by stimulation of the medial septum. Depressive influence of medial septal area stimulation was increased by physostigmine and blocked by scopolamine. Population spikes evoked by stimulation of the perforant path of the intact group were equally suppressed (by 43%) during sensory stimulation evoking natural theta, after physostigmine and after medial septal area stimulation. In the group of animals without medial forebrain bundle these influences resulted in a complete suppression of field potentials; scopolamine restored them. It is concluded that the main function of the septohippocampal cholinergic input consists of filtering out the signals appearing at the background of theta-rhythm triggered by a previous signal, thus preventing their interference with its processing and registration. PMID- 8506032 TI - Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit- IV. Sensory stimulation. AB - Modifications of responses of hippocampal neurons to sensory stimuli at the background of increased endogenous acetylcholine level (injection of physostigmine) and during blocking by scopolamine were analysed in the chronic alert rabbit. A significant decrease of reactivity (about 40%) of hippocampal neurons to sensory stimuli occurred after physostigmine injection, inducing stable theta modulation. Suppression and decrease of inhibitory responses (including initial reset phase) and of some excitatory reactions (including on effects) were observed. However, a limited group of excitatory responses was augmented and prolonged under physostigmine action. Scopolamine, which blocked electroencephalogram theta-rhythm, did not change the responsiveness of hippocampal neurons. Some of the inhibitory and excitatory effects of sensory stimuli, especially on-responses, were strongly facilitated. Tonic responses were shorter, but they were stably reproduced without typical gradual habituation. All these effects were also present in the hippocampus after basal undercutting of the septum, which eliminates ascending brainstem input. It is suggested that under normal conditions a new or significant sensory stimulus evokes, in the hippocampus, an initial inhibitory reset of neuronal activity with subsequent coordinated triggering of rhythmic theta modulation by the septal input and arrival of the cortical input signal phase-locked to it. During the period of theta triggered by the stimulus, its processing and fixation in memory occurs, while the other, interfering stimuli, which are not phase-locked to the ongoing theta activity, are actively filtered out. Thus, septohippocampal interactions may participate in the organization of selective attention as a necessary condition for memory trace formation. PMID- 8506033 TI - [Substernal goiter: new diagnostic methods and treatment]. AB - The authors report 47 cases of substernal goiters operated between 1971 and 1990. Forty-five patients had mediastinal-cervical-goiters (g.c.m.) and 2 had ectopic goiter (g.e.). Cervicotomy was performed in the 45 g.c.m., in 3 cases associated with sternal "split". The g.e. were treated with thoracotomy. Computed Tomography (TC) has been performed since 1984 in 26 patients; Magnetic Resonance (RM) since 1987 in 6 patients. The diagnostic accuracy for TC was 84.6% and 100% for MR on anatomical-topographic-definition, and 80.8% and 83.3% for presumptive diagnosis of nature, respectively. Considering the high diagnostic accuracy, the possibility to reconstruct the images in sagittal and coronal planes, the RM seems to be the elective diagnostic procedure for all substernal goiters. PMID- 8506034 TI - [Identification and preservation of the parathyroid glands in thyroidectomy using methylene blue]. AB - The risk to the parathyroids in thyroid surgery is widely known. Postoperative parathyroid insufficiency occurs because of accidental devascularization of one or several glands, or infarction due to manipulation, or resection within the thyroid lobe. The prevention of this complication requires a careful surgical technique which limits any injury of the parathyroids. A simple, safe and cheap method to improve the identification of these glands is the preoperative intravenous infusion of methylene blue, that results in a distinct staining of the parathyroids. The authors describe their experience with this useful procedure which helps to reduce the incidence of hypoparathyroidism after total and near total thyroidectomy. PMID- 8506035 TI - [Lateral access in thyroidectomy. Technique and indications]. AB - The technique of thyroidectomy, systematically carried out, by the authors, with a lateral approach since 1987 in thyroid reoperations for benign and malignant relapses and sometimes even in primary operations, is presented. The authors point out that lateral way is both technically advantageous in reoperations and moreover oncologically in prethyroid muscles's malignant involvement, but it does not represent an alternative to median access that, in the first instance, is the elective one. Because of the lateral vascular ligatures, in order to preserve the recurrent nerve, its location is mandatory. PMID- 8506036 TI - [Anastomotic pseudoaneurysms of the femoral bifurcation. Clinical experience]. AB - The authors report their experience of the treatment of anastomotic pseudoaneurysms of the femoral tripod. The paper analyses 231 cases treated over the past 8 years by the Division of Vascular Surgery using an alloplastic prosthetic implant in correspondence with the femoral tripod. Pseudoaneurysms were observed in 23 patients (9.8%) and emergency corrective surgery was required in 10 cases (43%) and elective surgery in 13 (56.5%). A total of 6 trans obturator by-passes, 2 femoro-femoral by-passes using the saphena vein, 2 axillo popliteal by-passes, 8 resections and re-implants, and 5 ligatures were performed. Immediate permeability was obtained in 15 patients, whereas 5 were amputated at the thigh and the remaining patient undergoing ligature preserved the limb but with chronic ischemic symptoms; 2 patients died. In the long-term follow-up of those patients who were permeable on discharge, permeability had persisted in 5 (83%) treated with trans-obturator by-pass and in 7 (87%) who had undergone resection and re-implant. The remaining axillo-popliteal by-pass had thrombosed after 6 months but the patient had not lost the limb. The authors underline the unpredictability of this pathology and analyse the causes which may provoke the development of this complication which inevitably leads to thrombosis or hemorrhage. However, suture materials (continuing pseudoaneurysm in spite of not using silk), the infective etiology (the extreme difficulty of obtaining a positive bacteriological culture) and the inguinal region (onset of pseudoaneurysm during aorto-femoral by-pass but hardly ever during femoro popliteal by-pass) may be contributory causes but not decisive factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506037 TI - [Crossectomy combined with sclerosis in the ambulatory treatment of varicose veins]. AB - This paper focuses on the advantages of an outpatient technique in the treatment of the 1st various syndrome based on crossectomy and complementary sclerotherapy to eliminate the proximal reflux. In addition to the speed, low costs and total absence of discomfort for the patient, this method results in a low percentage of easily correctable failures provided the patients to be treated are carefully chosen. Selection involves a preoperative screening phase based on anamnesis, semeiological tests, Doppler and evaluation of tibial venous pressure, as well as careful topographical mapping of proximal refluxes which allow a correct postoperative follow-up in the event of possible recidivation (14.3% based on the authors' experience). The surgical technique used entails an accurate crossectomy with full exposure of the SF crosse (??) and its affluent branches, and subsequent sclerotherapy with atoxysclerol in a variable quantity and % as required. Of a total of 91 cases treated with a 3-year follow-up, 5 cases of recidivation were observed during the first year and 8 during the third. In both cases postoperative pressure values in the tibial veins were considerably higher than in other patients and recidivation occurred through perforating sclerosed recanalised vessels. PMID- 8506038 TI - [The effects of protein-energy deficiency in candidates for gastric resection]. AB - The nutritional status of patients subjects to surgical operations represent an important element in determining the incidence of morbidity and mortality. We have examined 19 patients suffering both from benign and from malignant pathology subjected to a gastric resection and treated in the preoperative period for 7-8 days and in the postoperative period for 8-10 days with parenteral nutrition. Nutritional valuation was carried on at the time of admission, in the postoperative period and in proximity to discharge; an accurate observation of possible associated was also carried on. The comparison with the not treated with a nutritional support has shown a smaller incidence in complications of a general character and also in those connected with the operation and a reduction in the postoperative stay in hospital. PMID- 8506039 TI - [Verrucous carcinoma of the oral cavity. Personal experience with combined chemo surgical treatment]. AB - Following an introduction regarding the anatomo-pathological and clinical aspects of verrucous carcinoma of the oral cavity, the authors review several recent reports concerning the prognosis and treatment of this tumour and its possible evolution. This is followed by a wide-ranging discussion of the differing opinions put forward by various researchers regarding the possible role of radiotherapy and in particular the high risk of triggering off latent forms and provoking the differentiated and more aggressive forms of carcinoma. The authors then illustrate their experience of integrated chemo-surgical treatment, excluding radiotherapy, administered over the past six years to patients who were brought to their attention suffering from this form of carcinoma. PMID- 8506040 TI - [Carcinoid tumors of the appendix. Review of the literature and two case reports]. AB - Gastrointestinal carcinoids are infrequent but at the same time hardly rare tumours. They are often chance findings but, as is clearly reported in the literature, their potential malignancy should not be overlooked. They are most commonly localised in the appendix. The authors describe two case reports of carcinoid tumours of the appendix, one of which was diagnosed during left hemicolectomy due to Crohn's disease and the other during acute appendicitis. Prognostic and therapeutic problems are discussed in the light of the most recent literature. PMID- 8506041 TI - [Meckel's diverticulum. Case contributions]. AB - Eight cases of Meckel's diverticulum observed by the authors are reported. Different investigative methods, clinical and surgical aspects are discussed. Even asymptomatic Meckel's diverticulum discovered incidentally at surgery should usually be removed. PMID- 8506042 TI - [Mucocele of the appendix. Some diagnostic features]. AB - The description of a case of mucocele of the appendix shows the difficulties of arriving at a preoperative diagnosis. Following an analysis of the diagnostic features it's possible to affirm that only surgery can confirm the diagnosis with the histological result. Careful surgical dissection is very important when a malignant tumor is suspected. PMID- 8506043 TI - [Kaposi's sarcoma--classic form. A rare familial case]. AB - Although Kaposi's sarcoma became very well-known with the outbreak of AIDS, this pathology in the classic Mediterranean form is still unusual and obscure. Nowadays we identify four types of Kaposi's sarcoma: 1) the classic Mediterranean form, 2) the endemic African one, 3) the therapeutical in immunosuppressed patients, 4) the epidemic AIDS-related one. We report a very rare case of familial Kaposi's sarcoma: the father (72 y.o.) manifested Kaposi's sarcoma in 1989 with several angiomatoid nodules on the penis and hands; the son (31 y.o.) presented in 1991 only one little nodule on the penis. The right therapy in these cases (patients with a small number of localizations) was to remove all the tumors and to wait: whereas in other cases it's preferable to use radio- or chemo therapy or immunomodulator agents. We studied the patients and identified their form of Kaposi like the classic one not completely related (the son) to the HLA DR5, which is the HLA-phenotype most frequent in this sarcoma. Moreover we stress the rarity of genital localization in the classic form, instead it is very common (20%) in the AIDS-related one. PMID- 8506044 TI - [Subclavian steal syndrome. Clinical aspects and therapeutic problems]. AB - Cerebrovascular disease is a leading cause of morbidity and mortality in Italy. Although atherosclerotic involvement of the carotid artery is more prevalent, some patients suffer from stenosis of the subclavian artery, usually proximal to the origin of the vertebral artery. Neurological symptoms result from reversed flow in the vertebral artery, so-called "subclavian-steal". This collateral pathway may rob the posterior circulation of perfusion to the degree of producing episodes of vertebrobasilar insufficiency. The authors have therefore reviewed their experience with this disease and present their findings, therapeutic procedures and short-term results. During 1990 four patients affected by "subclavian-steal syndrome" were observed at the Surgical Department of Montecchio Maggiore Hospital (VI). Two patients were operated on and axillo axillary bypass operations were performed (with a 5 mm Gore-tex graft). The goal of surgical treatment is to alleviate cerebrovascular symptomatology by restoring flow to the subclavian artery distal to the occlusion. Axillo-axillary bypass offers distinct advantages over the alternative methods such as transthoracic procedures or carotid-subclavian bypass. Axillo-axillary bypass is a technically simple procedure with very good results and minimal complications. It avoids sternotomy, thoracotomy and clavicular resections: the carotid artery is not involved in the procedure. The authors conclude that axillo-axillary bypass is a cheap, safe and effective treatment for symptomatic subclavian artery insufficiency. PMID- 8506045 TI - [Morphologic and endocrine changes in the male reproductive system after porta caval anastomosis in rats. Experimental research]. AB - Quantitative alterations of the sexual hormones are present in cirrhotic patients whose testicular volumes are decreased with tubular atrophy in more than 50% of cases. The authors performed an experimental study utilizing end-to-side portacaval anastomosis in the rat in order to evaluate the consequences of the complete interruption of the portal blood to the liver in the male genital system, i.e. testicular alterations, due to the missing hepatic inactivation. Forty male Sprague-Dawley rats were used for this study. Twenty rats were subjected to end-to-side porta-caval anastomosis according to Lee, 10 rats underwent sham-operation while the remaining 10 rats were utilized as negative controls. The rats were weighed and necropsied three and six months after surgery and the liver and genital organs were weighed. In rats subjected to porta-caval anastomosis loss of weight was shown, about 20 g three months after surgery and 30 g six months after surgery, while other rats (sham-operated and negative controls) showed an increase of its weight, about 60 g after three months and 80 g after six months. In rats subjected to porta-caval anastomosis the liver was hypotrophic and its weight was decreased in comparison with the control group. In the same rats testicular volumes were decreased and hypotrophic in comparison with the control groups with average length 0.5 to 1 cm, while control groups showed values of 1.7 to 2.5 cm. Testosterone levels were 0.50 ng/ml in rats subjected to porta-caval anastomosis while in control groups the levels were 2.20 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506046 TI - [Hyperparathyroidism resulting from chronic renal insufficiency. Diagnosis and therapy]. AB - Twenty-seven patients, eighteen females and nine males, with chronic renal failure and secondary hyperparathyroidism, were treated by subtotal parathyroidectomy. Bone pain, in 24 patients, hypercalcemia in 2 and severe pruritus in 1 were the main indications to surgery. Result evaluation was possible in twenty four patients. Bone pain disappeared or was reduced in 20/22 patients. Serum alkaline phosphatase and PTH returned to normal in 21/24 patients. There patients had persistent hyperparathyroidism because of inadequate surgical exploration. Another group of seven patients with secondary hyperparathyroidism recalcitant to medical therapy or relapsing after subtotal parathyroidectomy was treated with calcitriol ev. After nine months of follow-up PTH and alkaline phosphatase serum levels were reduced to normal value in all patients. PMID- 8506047 TI - [The guaiac test and colorectal pathology. Clinical evaluation]. AB - The paper reports the results of a study carried out in 187 out-patients who were examined for various reasons. A guaiac test was performed in all patients and those with positive results were further examined using more complex methods. The results obtained showed that, due to its high levels of sensitivity and specificity, as well as its low cost, the "Hemoccult test" still represents the most suitable means for the mass-screening of non-selected populations. PMID- 8506048 TI - [Prophylactic cholecystectomy in bariatric surgery]. AB - In this paper the authors discuss about prophylactic cholecystectomy in bariatric surgery. Having analyzed the mechanisms that increase bile lithogenicity after bariatric surgery, they evaluate advantages and disadvantages of prophylactic cholecystectomy. They present 53 obese patients submitted to biliopancreatic diversion and prophylactic cholecystectomy for surgical treatment of morbid obesity, because of the high incidence of pathological findings in the specimens and the absence of surgical complications related to cholecystectomy, the authors, in agreement with the literature, suggest routine cholecystectomy as an obvious adjunct to bariatric surgery. This attitude protects against the higher risk of subsequent cholecystectomy and against the misinterpretation of non invasive diagnostic tests too, because of known limits of echography in obese people. PMID- 8506049 TI - [Qualifications for the validity of screening for occult fecal blood in the early diagnosis of colorectal cancer]. AB - The discovery of a polyp is nowadays unanimously considered a harbinger of colorectal cancer. Bleeding is one of the most meaningful symptoms of this intestine pathology. Occult blood tests in stool as a screening technique for colorectal cancer can be considered an effective diagnostic means to prevent and detect this kind of neoplasm at an early, curable stage. There are two kinds of commercially available tests for detection of occult fecal blood loss: Guaiac tests and immunologic tests. Those people who are responsible for these screenings should have at disposal well-working diagnostic instruments and experienced physicians. Only on these conditions patients with positive results on screening tests can undergo an effective second level diagnostic surveillance. In this way substantial results can be obtained by means of this kind of secondary prevention. PMID- 8506050 TI - [Warthin's tumor. Review of the literature and personal experience]. AB - Warthin's tumour is a much debated clinical case-characterised by the presence of epithelial proliferation and lymphoreticular stroma. Numerous controversies concern this type of tumour so much so that recently is was even denied that it can be considered a real tumour. The present paper aims to review the state of the art and report the authors' personal experience. PMID- 8506051 TI - [Two cases of adrenal myelolipoma]. AB - The paper reports two rare cases of adrenal myelolipoma which were referred to the authors' attention. This is a functionally inactive benign tumour made up of fatty tissue and foci of hemopoietic cells. It is often diagnosed due to the compression disorders caused to adjacent structures, whereas at other times it is identified by chance during the course of diagnostic tests carried out for other pathologies. PMID- 8506052 TI - [Merkel cell carcinoma of the skin. Two clinical cases]. AB - In this study are described two clinical cases of Merkel cell tumor treated in the first half of 1991. The MCC is a rare primary skin tumor with an aggressive biologic nature. The elective therapy of primary sites is surgical management with lymphadenectomy although this kind of treatment is debated. Local recurrence high incidence requires a frequent and careful follow-up with possibility of second surgical treatment in the cases without metastasis and a radiochemotherapy in the patients affected by systemic recurrences. PMID- 8506053 TI - [Oleoma of the knee. A clinical case]. AB - Authors describe clinical and anatomo-pathological features of a case of oleoma of the left knee, repaired with success through the rotation of a muscular flap of lateral gastrocnemius and application of dermo-epidermal graft. Postoperative follow-up was regular; prompt healing and morpho-functional restoration of involved structures was complete. PMID- 8506054 TI - [Salivary immunoglobulins in the diagnosis of primary Sjogren's syndrome]. AB - The salivary concentrations of immunoglobulins and total proteins and the salivary flow rate (measured by the method of Deniker et al.) were determined in 29 patients with keratoconjunctivitis sicca and xerostomia and in 11 healthy subjects. According to Fox criteria the group pf 29 patients was divided into two groups: 14 patients with primary Sjogren's syndrome (pSS) and 15 patients with sicca syndrome (SS). The IgA salivary levels were significantly higher in the patients with pSS than in the patients with SS (p < 0.05) and in the healthy subjects (p < 0.001). Moreover the IgG and IgM salivary levels in the first group of patients were higher than in the group of patients suffering from sicca syndrome (p < 0.05) and in the control group (p < 0.02). The salivary flow rate of the patients with pSS and sicca syndrome was lower when compared with the control group (p < 0.005). No significant correlation was found between the salivary flow rate and the immunoglobulins in the three groups of patients. The salivary flow was inversely correlated (p < 0.01) only with the IgA levels in all 40 subjects. The salivary total proteins were significantly elevated in pSS patients when compared with the SS patients (p < 0.04) and with the control group (p < 0.01). The immunoglobulins/total proteins ratios in saliva were significantly higher in the first group than in the other groups (p < 0.005) for the IgG and in the first group than in the SS patients (p < 0.05) for the IgM; no significant differences were noted for the IgA. The bioptic focus scores, graded according Greenspan's criteria, of minor salivary glands of 20 patients with pSS or sicca syndrome were directly correlated with a high significance (p < 0.001) to IgG salivary levels and with a lower significance (p < 0.05) with IgM salivary levels. No significant correlation was found between the bioptic focus scores and the IgA levels. The present results demonstrated a high specificity (100%) and a good sensitivity (86%) of the assessment of salivary IgG for the diagnosis of pSS. The sensitivity of the salivary levels of IgA was higher than that of IgG (93%) but the specificity was low (50%); on the contrary the specificity of the assessment of salivary IgM was good (92%) but the sensitivity was low (60%). This study therefore indicated that the assessment of salivary IgG has a great value for the diagnosis of pSS because IgG levels are related to the amount of lymphoplasmocytic infiltration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8506056 TI - [Oxidative stress in patients undergoing general anesthesia]. AB - The alterations in the normal biological oxide-reductive balance can be due both to an increase of the plasmatic concentration of the free radicals and to the less of the protective mechanism. These conditions lead to damage to cellular structure by the mechanism of lipoperoxidation, particularly in the liver, in the kidney and in the central nervous system. In this study we have studied the lipoperoxidative effects of the use of anesthetic drugs. PMID- 8506055 TI - Metabolic aspects and sympathetic effects in the obese subject undergoing exercise testing. AB - An impaired plasma Epinephrine (E) and Norepinephrine (NE) response has been described in obese patients during physical exercise. Serum potassium level is influenced either by physical exercise or by the adrenergic system. We studied 12 young obese patients and 12 young controls, all without any cardio-respiratory disorders, who underwent a cycloergometric test with steps of 20 watts every four minutes until exhaustion. During the test we recorded serum potassium levels, E and NE, insulin, glucose and RQ to confirm or not the observation of the reduced adrenergic response in obese patients. During exercise, although both groups reached a not significantly different mean peak value of maximal activity, E and NE increased, more in the controls than in the obese subjects (at peak of exercise 221 +/- 44.1 vs 71 +/- 21.5 pg/ml respectively for E; 2035 +/- 164.8 vs 1141 +/- 313.7 pg/ml respectively for NE). RQ was constantly lower in the obese patients than in the normals both during and after the stress. In both groups potassium increased significantly, but the obese patients had a significantly lower increment at peak of activity when compared to the controls (delta K+: 0.52 +/- 0.11 vs 1.007 +/- 0.17 meq/l respectively, p < 0.05). Insulin and glucose had a behaviour in line with literature in both groups. The behaviour of potassium could be an index of a higher effect of beta-adrenergic system in obese patients than in normals despite the different increases of catecholamines in the two groups. This hypothesis may agree with the preferential metabolic use of fatty acids in our obese patients as indicated by RQ values. PMID- 8506058 TI - [Life habits and impotence]. AB - The authors propose their experience of 595 men complaining of erectile dysfunction. Relationships among erectile dysfunction, taking specific medicaments (hypotensive agents) and habits (smoking) are considered. A collaboration among specialists in the management of impotent patients has been proposed. PMID- 8506057 TI - [Treatment of chronic brucellosis with ciprofloxacin. Personal experience]. PMID- 8506059 TI - [Diabetic foot. A clinical case]. AB - Diabetic neuropathy may cause an alteration of the function of the muscles of the sole of the foot. This is at the origin of the chronic dislocation of the articular heads, mainly of the little metatarsal bones (neuro diabetes arthropathy), with formation of areas of pathological pressure. The tissues below being chronically under pressure are affected by trophic lesions called "plantar perforating disease". Recovery may be obtained by not exposing the injured area of the foot to pressure and through careful local therapy. This doesn't prevent disease from appearing again, even though some specially conceived soles are being used, aiming at a correct weight redistribution on the sole of the foot. The clinical case we are describing applies to a man affected by insulin dependent diabetes mellitus, with relapsing diabetic foot ulcers, in spite of him using a specifically designed sole. Such lesion is aggravated by a serious infection which, by gradually penetrating in depth, leads to osteomyelitis, affecting the 5th Metatarsal head. The bone area, dislocated by neuroarthropathy, was presumably responsible for the persisting plantar lesion. The amputation of this infected necrotic structure, has led to the overcoming of the serious septic problem. By eliminating the bone link responsible for the transmission of the pathological pressure, the plantar lesion the patient had been suffering from for a long time, has consequently disappeared. PMID- 8506060 TI - [Decisive scintigraphic diagnosis in a case of Borrelia infective sacro-iliitis]. AB - The authors describe one case of infections sacro-iliitis caused by Borrelia, where the diagnostic procedures by conventional radiology, computerized tomography and nuclear magnetic resonance imaging have not permitted the localization and the assessment of joint inflammatory disease. The bone "theree phases" scintiscan by 99m Technectium-methylene diphosphonate (99mTC-MDP) has made it possible to localize on left sacro-iliac synchondrosis a modification of radioactivity, due to inflammations. Next microbiological studies gave a positive result for borrelia. The authors finish by underlying the importance of the nuclear medicine methods in the screening of infective osteo-arthritis. PMID- 8506061 TI - [Pregnancy complication in homozygous (delta beta) zero-thalassemia. A clinical case]. AB - A case of a pregnant woman suffering from homozygous (delta beta) zero thalassemia clinically running as thalassemia Intermedia is described. In this patient pregnancy could not follow its normal course and was interrupted in the 24th week, because of endouterine death of the foetus due to complications such as serious haemolytic anaemia following transfusional alloimmunisation and the presence of portal vein thrombosis. In this article the literature is reviewed and the need is shown for all thalassemic patients to be tested for the various blood antigenic systems, so that transfusional reactions can be avoided. Stress is laid on the importance of erythropoietin both in the pathogenesis of haematological and rheological modifications in thalassemic patients and also as a trigger in serious thrombotic complications. PMID- 8506062 TI - [Plasmocytoma of the testis. Description of a clinical case and review of the literature]. AB - Extraskeletal involvement of the testis during multiple myeloma is a rare disease; primary extraosseus myeloma of the testis is even more unusual, and shows progression to typical multiple myeloma after orchiectomy in most cases. A case-report of a multiple myeloma with testicular involvement is discussed; radiotherapy was performed successfully, instead of surgery, but diffuse skeletal lesions showed progression in spite of chemotherapy. A short review of the literature on this subject is made. PMID- 8506064 TI - [Calculi and sludge in the gallbladder during pregnancy]. AB - Ultrasound examination surveys carried out during puerperium or pregnancy have demonstrated the presence of biliary sludge and gallstone with a percentage of the examined women varying from 30% to 40%. Our aim was to evaluate the incidence of biliary sludge and gallstones during pregnancy and the natural history of this pathology after delivery in our rural population. Fifty six pregnant women entered the study. The pregnant women were subjected to ultrasonography during the 12th-14th and the 34th-36th week of amenorrhea, and two weeks after delivery. Women with biliary sludge or gallstones were subjected to a further ultrasound examination 12 months after delivery. At the first ultrasonography, women were questioned about menarche, menstruation (rhythm, intensity and period), previous pregnancies, number of deliveries, use of oral contraceptives and possible abdominal symptoms connected with the pathology of gallbladder. Besides, in order to form the body mass index (BMI) [weight (kg)/height (m)2], weight and height were obtained from each subject. Before the second ultrasonography, women were questioned about abdominal symptoms connected with the pathology of gallbladder. It was assessed the weight in order to calculate the ponderal increase during pregnancy. Biliary sludge or gallstones were found at ultrasound examination in: 5 out of 56 women in the first trimester (one woman with gallstones, 4 with sludge); 9 out of 49 women examined in the third trimester (2 women with gallstones, 7 with sludge); 2 out of 46 women examined were still affected by gallstones two weeks after delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506063 TI - [Modification of immunologic parameters in physiologic pregnancy]. AB - Changes in lymphocyte subsets in whole blood of normal pregnant women were examined by flow cytometry. From the first trimester and throughout pregnancy, the count of B cell subset remain unchanged. On the contrary, the percentage of "helper" lymphocytes decreased in the first trimester, increase in the third. These changes of lymphocyte subsets may indicate suppression of immunological activity during pregnancy. PMID- 8506065 TI - [Laparoscopic total hysterectomy and its complications]. AB - The Authors base their experiences on 135 total laparohysterectomy operations. Of a sample of 39 cases the postoperative lapses have shown complications with a percentage of 28.87% so divided: 25 infectious complications (18.51%); 9 thrombophlebitis (6.66%); 3 vascular lesions (2.22%); 2 intestinal lesions (1.48%). They end by saying that to have good clinical conduction of such operations it is necessary to respect the specific hygienic and preventive rules. PMID- 8506066 TI - [Use of triptorelin in the medical treatment of uterine myoma]. AB - Following the introduction of GnRH analogue drugs the medical treatment of uterine myomatosis has been proposed. The use of these compounds in fact causes a reduction in mean plasma levels of 17-beta-estradiol which is reflected in the target tissue of myomas. Using this hormone-dependence as a starting Tryptoreline point, the study examined the volumetric changes induced by LH-RH agonist analogue, Tryptoreline, administered to a group of 15 selected patients. The results are encouraging: in all cases there was a marked reduction of tumour volume ranging between 30 and 40%. The therapeutic effect, however, gradually wore off following the suspension of treatment. For this reason, the use of this analogue should be reserved for premenopausal or younger patients for the treatment of menometrorrhagic episodes, or as a preoperative therapy in order to limit blood loss during surgery. PMID- 8506067 TI - [Treatment of secondary adolescent amenorrhea with purified FSH]. AB - The dysfunctional features of adolescent secondary amenorrhea are here considered: anovulation, immaturity of estrogenic feed back, multi-follicular ovary. We described the opportunity of using gonadotrophin in the treatment of hypogonadotrophic amenorrhea. Among 64 patients with menstrual delay, we examined a group of 23 selected girls, 21 of them affected by secondary amenorrhea and 2 affected by primary amenorrhea; their average age is 17 years. The selection excludes organic and psychiatric pathologies, while includes anovulation, low rates of FSH and inadequate response to LHRH test, multi-follicular ovary. Some patients were also affected by acne, hypertrichosis, weight disorders, emotional stress. The therapeutic approach with purified FSH (urofollitrophin) is described on an amount of 48 treatments. We used 75/225 UI/day at 3 degrees to 5 degrees/7 degrees of each menstrual cycle, and for 3/5 cycles. Doses are in some subjects modified during the treatment in relation to menstrual response. Hormonal, echographic and clinical evaluation were given before and after each treatment. The results of giving FSH demonstrate an 81.2% of immediate success, while an 43.7% up to 12 months. We observed a significant reduction of LH rates as well as estrogenic increase and subsequent menstrual response. Ovarian follicles increased in number and volume, while no hyperstimulation effects appeared. In general we suppose these data are satisfactory; nevertheless we point out the opportunity of only treat selected patients, even in considering the complaint due to this therapeutic engagement and the eventual consequent renouncing. PMID- 8506068 TI - [Estradiol benzoate test in the study of pituitary block induced by triptorelin]. AB - The suppression of the positive oestradiol (E2) feed-back mechanism was studied in 21 patients during treatment with long acting GnRHa-triptorelin 3.75 mg (Ipsen Biotech). A basal sample for FSH, LH and E2 evaluation was taken before a single administration of 2.5 mg of oestradiol benzoate (EB) i.m. at 24 and 48 hours later. The test was performed 1, 2, 3, 4, 5, 6 and 7 weeks after i.m. injection of GnRHa. The E2 concentration 24 hours after EB injection was > 400 pg/ml, able to induce, in physiological conditions, a positive feedback. In the other hand no FSH an LH rise was observed in all test after 1, 2, 3, 4, 5, 6 and 7 weeks from GnRHa administration. Our results show the absolute suppression of the positive feed-back mechanism during the treatment with a single dose of long acting tryptorelin 3.75 mg i.m., the same results were obtained until the 7th week after GnRHa administration. PMID- 8506069 TI - [Sports and pregnancy]. AB - In the absence of underlying cardiovascular, metabolic endocrine disease or other high-risk problems (threatened premature labour, conditions associated with an increased risk of prematurity, acute fetal distress), pregnancy can be considered a variation in the normal human physiologic condition. Beneficial effects can be realized from submaximal exercise programs, apparently without concomitant deleterious effects on the fetus, which continues to receive an adequate oxygen and nutrition supply during maternal and moderate exercise. The physician should advise women to be careful in their choice of sports and not to begin new activities or increase their intensity during pregnancy. The benefits of regular aerobic exercise are well known. The effect of anaerobic workouts during pregnancy is less clear. Nonetheless, women should be advised to avoid anaerobic training such as sprinting and interval work during pregnancy. Swimming is an excellent cardiovascular conditioner with minimal risk of orthopedic complication. Violent sports should be avoided. PMID- 8506070 TI - Increases in cytosolic Ca2+ in rat area postrema/mNTS neurons produced by angiotensin II and arginine-vasopressin. AB - It is well established that neurons in the dorsal medulla, including the area postrema and the medial nucleus tractus solitarius (mNTS), are involved in the central actions of circulating peptides such as angiotensin II (ANG II) and arginine vasopressin (AVP). This report describes a preparation that permits the identification and maintenance of area postrema/mNTS neurons in culture in which the cellular and potentially subcellular responses to neurotransmitters and neuropeptides on area postrema/mNTS cells can be investigated. Following 15-21 days in culture, the effects of ANG II and AVP on changes in intracellular Ca2+ concentration ([Ca2+]i) were examined. Both ANG II and AVP resulted in a rapid and transient increase in [Ca2+]i reaching maximum in 15 s and returning towards baseline values within 180 s. The ANG II-mediated increase in [Ca2+]i was almost completely abolished by the selective angiotensin AT1 receptor subtype antagonist, losartan (DuP 753). These results suggest that ANG II and AVP modulate area postrema/mNTS neuronal activity by increasing intracellular Ca2+. PMID- 8506071 TI - Vasoactive intestinal peptide stimulates type II thyroxine 5'-deiodinase and N acetyltransferase activities in dispersed pineal cells of euthyroid and hypothyroid rats. AB - The effect of vasoactive intestinal peptide (VIP) on thyroxine type II 5' deiodinase (5'-D) and N-acetyltransferase (NAT) activities were studied using pineal cells of euthyroid and hypothyroid rats. VIP activated 5'-D activity in a dose-dependent manner in both euthyroid and hypothyroid animals. However, basal and VIP stimulated activity was higher in pinealocytes from hypothyroid than in cells from euthyroid rats. VIP was also able to stimulate NAT activity but hypothyroidism did not induce modifications in its activity. Both 5'-D and NAT activities were stimulated not only by VIP, but also by isoproterenol, a beta adrenergic receptor agonist, and forskolin, a potent activator of adenylate cyclase activity. The results suggest that VIP may be involved in the physiological regulation of pineal 5'-D activity. PMID- 8506072 TI - Progesterone does not mediate the inhibition of pineal melatonin production during the rat proestrous night. AB - N-Acetyltransferase (NAT) activity and melatonin content were determined in pineal glands obtained during the proestrous stage of the rat estrous cycle. In control animals, both pineal NAT activity and melatonin levels were reduced during the first hours of proestrous night, as compared with day-time proestrous levels. The administration of antiprogestagen RU486, in a dose which blocked the preovulatory rise of serum luteinizing hormone and follicle-stimulating hormone levels, failed to prevent the reduction of pineal melatonin synthesis associated with the ovulatory events at proestrous night. These results suggest that estradiol, but not progesterone, might be the ovarian hormone responsible for the inhibition of pineal melatonin synthesis observed in the normal cycling female rat during proestrous night. PMID- 8506073 TI - X-ray probe microanalysis of Alzheimer disease soluble and insoluble paired helical filaments. AB - The paired helical filaments of Alzheimer disease, which have been shown to consist of both soluble and insoluble forms, were examined by X-ray probe microanalysis in order to determine if there existed differences in their elemental composition. The soluble paired helical filaments contained both sulfur and phosphorus, supporting their composition being enriched in a phosphorylated protein. The insoluble paired helical filament core structures, which retained their morphology after extensive protease digestion, contained only a small amount of sulfur over background, which suggests that they are not composed entirely of protein. This significant difference in sulfur and phosphorus indicates a difference in composition between the soluble and insoluble paired helical filaments, and that the paired helical filament core structures may attribute their insolubility to their being predominately non-proteinaceous. PMID- 8506074 TI - Localization of acetazolamide-resistant carbonic anhydrase III in human and rat choroid plexus by immunocytochemistry and in situ hybridisation. AB - Carbonic anhydrase is an essential metabolic enzyme of the central nervous system and has an important role in the production and regulation of cerebrospinal fluid. Although it has been known for over 30 years that inhibition of the enzyme with acetazolamide dramatically but not completely reduces the production of cerebrospinal fluid, the precise mechanism of the inhibitory action has been only recently revealed. In this study we present evidence that apart from carbonic anhydrase II, the catalytically highly active isozyme, carbonic anhydrase III, an acetazolamide-resistant and kinetically different isozyme could be demonstrated in the epithelial cells of the developing and mature rodent and human choroid plexuses. Both isozymes express intense immunostaining revealed with specific antisera, and by using in situ hybridisation histochemistry, carbonic anhydrase III mRNA was also observed. Since the kinetic properties and proportion of brain carbonic anhydrase III in the human choroid plexus are not revealed the function of this isozyme in choroid plexus is still to be determined. PMID- 8506075 TI - Focal increases in [3H]forskolin and [3H]phorbol 12,13-dibutyrate binding in the rat brain following lesions of the medial septum. AB - Quantitative autoradiography of [3H]forskolin binding to GS-adenylate cyclase and [3H]phorbol 12,13-dibutyrate (PDBu) binding to protein kinase C (PKC) was examined 21 days following ibotenate lesion of the rat medial septum. A significant reduction (-19%) in [3H]forskolin binding was observed at the lesion site in the medial septum compared to the sham-treated group. A significant increase in [3H]forskolin binding was demonstrated in the polymorph layer of the detante gyrus (19%) in animals with medial septal lesions whilst in all other brain regions, [3H]forskolin binding remained unaltered post-lesion. [3H]PDBu binding was significantly increased in the superficial layers (I-III) of entorhinal cortex (27%) following lesion of the medial septum, and remained unaltered in all other brain regions post-lesion. The nature and location of the alterations (namely elevations) in ligand binding sites remote from the lesioned area are supportive of plastic modifications of second messenger systems following denervation. PMID- 8506076 TI - Developmental expression of trkB and low-affinity NGF receptor in the rat retina. AB - Brain-derived neurotrophic factor (BDNF) promotes the survival of retinal ganglion cells, but these effects are dependent on the developmental stages, and a number of retinal ganglion cells are eliminated during pre- and neonatal stages. We have examined the expression of BDNF receptors, trkB and low-affinity nerve growth factor receptor (LNGFR), in the rat retina during these period using Northern blot analysis. The expression of trkB and LNGFR displayed two peaks during embryonic day 17 (E17) through postnatal day 1 (P1), and during P14-P17, indicating that it may play an important role in neuronal development and neuronal cell death. PMID- 8506077 TI - Spatio-temporal representation of sound intensity in the guinea pig auditory cortex observed by optical recording. AB - The spatio-temporal representation of sound intensity in the guinea pig auditory cortex was studied by optical recording with the aid of a voltage-sensitive dye. Changes in light intensity due to neural activity induced by sounds at various pressure levels were recorded with a 12 x 12 array of photodiodes. The amplitudes of the responses were displayed as sequential two-dimensional images. The iso intensity bands revealed by neural activity were orthogonal to the isofrequency bands of tonotopical organization in the anterior field and dorsocaudal field. The frequency-intensity representation through the orthogonal organization varied with time. This mechanism may be adapted to the auditory cortex to sequentially process the three parameters of sound: frequency, intensity, and time. Furthermore, a new field was found in the ventrocaudal region of the auditory cortex. This field showed tonotopicity, but high thresholds. PMID- 8506078 TI - Modulation of IGF-2 expression during growth and differentiation of human neuroblastoma cells: retinoic acid may induce IGF-2. AB - Insulin-like growth factor 2 (IGF-2) is the major autocrine growth factor for neuroblastoma. IGF-2 mRNA can just be detected in SK-N-BE(2) cell line; higher levels are present in two clones derived from it [BE(2)-C; BE(2)-M17]. IGF-2 mRNA is increased by retinoic acid (RA) only in the clones. IGF-2 expression/induction is more marked in BE(2)-M17, which shows more RA-resistance (evaluated as growth inhibition, neurite outgrowth and induction of programmed cell death). Under RA exposure, the parental line shows a more pronounced growth inhibition, neurite outgrowth and programmed cell death, as compared to its clones. BE(2)-C cells also express type 1 IGF receptor mRNA, though with a different time course than for expression of IGF-2. The data suggest that IGF-2 expression is correlated with growth, and may counteract the growth retardation, neurite outgrowth and programmed cell death effects of retinoic acid. Therefore the autocrine pattern of IGF-2 production by neuroblastoma cells may promote RA-resistance. PMID- 8506079 TI - The neuroanatomic binding pattern of [125I]atrial natriuretic factor in the Japanese quail brain. AB - Application of quantitative autoradiography technique provided a discrete anatomical distribution pattern of the atrial natriuretic factor (ANF) in the Japanese quail, Coturnix coturnix japonica, brain. The highest binding levels of [125I]ANF were shown to occur in telencephalon areas, such as fasciculus diagonalis Brocae (232 fmol/mg protein), septum (194 fmol/mg protein) and olfactory bulb (153 fmol/mg protein), and in posterior sites, such as nucleus interpeduncularis (177 fmol/mg protein), while lower levels (> 51 < 87 fmol/mg protein) were found in the hypothalamic sites of the diencephalon. The similar ANF receptor density levels in some brain areas of the quail as well as both mammalian and non-mammalian species suggest that this peptide might be involved in osmoregulatory activities (at the brain level) and furthermore indicate a probable functional conservation of ANF in vertebrates. PMID- 8506080 TI - Loss of large neurons and occurrence of neurofibrillary tangles in the tuberomammillary nucleus of patients with Alzheimer's disease. AB - We studied the number of large-sized neurons and neurofibrillary tangles (NFT) in the tuberomammillary nucleus (TM) of the hypothalamus from cases with Alzheimer's disease (AD) and age-matched controls. Numerous NFT were found in TM of AD. However, NFT was never observed in this nucleus of age-matched controls. The number of large-sized neurons was significantly reduced in AD compared with that in controls. Since the majority of large neurons in TM appear to correspond to histamine neurons, the loss of large neurons observed in TM may, at least partly, cause the histaminergic dysfunction in AD brain. PMID- 8506081 TI - Alz-50 immunoreactivity in the central nervous system of adult rat and primate. AB - The purpose of this work was to investigate the distribution and density of Alz 50 immunoreactivity in the central nervous system of normal adult and cortically injured rats and primates (Cercopithecus aethiops). In control animals of both species a consistent pattern of fiber immunoreactivity was detected within the hypothalamus (arcuate nucleus and median eminence) and the spinal cord (posterior horn and dorsal root nerve). Immunoreactive perikarya were predominantly observed throughout the anterior region of the third ventricle. An identical localization and density of Alz-50 staining was observed in lesioned animals. These experiments reveal that the pattern of Alz-50 immunoreactivity is not affected by the neurodegenerative processes that follow the cortical devascularizing lesion. These observations suggest that the monoclonal antibody Alz-50, besides recognizing cytoskeletal components in degenerating neurons, reacts with specific epitopes located in the hypothalamus and spinal cord of normal mammalian central nervous system. PMID- 8506082 TI - Tetanus toxin inhibits depolarization-induced [3H]serotonin release from rat brain cortex synaptosomes. AB - The effects of tetanus toxin on depolarization-induced [3H]serotonin release from superfused rat brain cortex synaptosomes was investigated. Two hours' preincubation of the synaptosomes with tetanus toxin resulted in a concentration dependent decrease of K(+)-stimulated release, with an IC50 of about 30 nM (4.5 micrograms/ml); this inhibitory effect was blocked by a previous incubation of the tetanus toxin with antitoxin serum. Tetanus toxin had no effect on reserpine induced release, a model of Ca(2+)-independent release. These results indicate that tetanus toxin is able to alter the exocytotic machinery of serotoninergic terminals, in agreement with results obtained with other neurotransmitters. They also indicate that serotoninergic terminals possess the receptor for tetanus toxin. These findings are in line with in vivo observations suggesting a role for serotoninergic system in tetanus intoxication. PMID- 8506083 TI - Recovery of auditory structure and function in neonatal chicks exposed to intense sound for 8 days. AB - This paper describes hearing loss and recovery as well as cochlear damage in chicks, after a 200-h exposure to an intense pure tone, and compares the results to similar data following a 48-h exposure to the same sound. The results revealed that the magnitude of initial hearing loss and the rate of recovery were nearly the same for both exposures. The initial cochlear damage produced by the 200-h exposure, however, was less severe than that seen after the 48-h exposure. In addition, new hair cells were observed in the lesion area immediately after the 200-h exposure. However, after the 48-h exposure, they were first identified after several days of recovery. These observations were consistent with the conclusion that cochlear repair began during the longer exposure itself. The fact that hearing loss and recovery was the same for the two exposure conditions, while the level of cochlear damage differed, suggests that functional recovery depended on processes other than the regeneration or repair of hair cells and supporting cells. These other processes are considered. PMID- 8506084 TI - Central respiratory modulation of facial motoneurons in rats. AB - Facial motoneurons (FMN) were recorded intracellularly in Sprague-Dawley rats anesthetized with halothane. The animals were vagotomized, paralyzed, and artificially ventilated. The average membrane potential of the cells was 62.6 +/- 1.9 mV and their input impedance ranged from 5 to 30 M omega (9.8 +/- 1.1 M omega, n = 38). The membrane potential of most FMNs varied throughout the central respiratory cycle and four distinct patterns were detected. Type I (post inspiratory) cells (21/44) showed a two-phase Cl(-)-mediated hyperpolarization during the respiratory cycle, one during central inspiration and the second during late expiration. Type II cells (early inspiratory, n = 10) showed early inspiratory depolarization. Type III (n = 2, stage-2 expiratory) cells displayed late expiratory depolarization and one cell (type IV or throughout inspiratory) exhibited expiratory Cl(-)-mediated hyperpolarization. The remaining 10 cells showed no detectable respiratory modulation. The results reflect the heterogeneity of the central respiratory modulation of FMNs and suggest that these cells receive both excitatory and inhibitory inputs from elements of the central respiratory pattern generating network. PMID- 8506085 TI - Gonadotropin-releasing hormone (GnRH) neurons in the hypogonadal mouse elaborate normal projections despite their biosynthetic deficiency. AB - This study was undertaken to determine whether gonadotropin-releasing hormone (GnRH) neurons in the mutant hypogonadal (hpg) mouse can establish axonal connections with their target despite their failure to synthesize and secrete the GnRH neuropeptide. Normal and hpg males received intraperitoneal injections of the retrograde tracer Fluoro-Gold. This tracer does not cross the blood-brain barrier and hence is taken up only by neurons in the central nervous system whose axons terminate on fenestrated capillaries, such as the capillaries of the median eminence. The brains of the injected animals were processed for in situ hybridization to visualize GnRH transcribing cells. In 3 hpg males 64.1 +/- 5.6% of GnRH transcribing cells contained Fluoro-Gold, while 55.8 +/- 6.4% of the cells in 3 normal males had Fluoro-Gold. Thus, we have demonstrated that secretory-deficient GnRH neurons can establish axonal connections with their primary secretory target, the median eminence. We conclude that the capability of GnRH neurons to recognize and interact with their target is not dependent upon their neurosecretory function. PMID- 8506087 TI - Special issue: Transplantation. PMID- 8506086 TI - Brainstem auditory evoked potentials in experimental autoimmune dementia. AB - Cognitive dysfunction may be induced in rats by immunization with cholinergic neuronal antigens and is associated with degeneration of nuclei in the septum and hippocampus and white matter tracts in the forebrain. Such rats are a putative model of Alzheimer's disease named experimental autoimmune dementia (EAD). The aim of the present study was to investigate brainstem auditory evoked potentials (BAEP) in EAD rats in order to define the extent of white matter tract involvement in this model. Clear reproducible evoked potentials were obtained and the normal range of BAEP in rats was established in adjuvant immunized controls. Measurements of inter peak latencies (IPL) I-IV in 9 EAD rats revealed that they were not significantly prolonged (3.00 +/- 0.22 ms, mean +/- S.E.M.) compared to 9 controls (2.80 +/- 0.08 ms), (P > 0.2, Student's t-test). The lack of significant change in IPL I-IV is compatible with preliminary histological findings and indicates that brainstem structures are generally unaffected in EAD. PMID- 8506088 TI - First-hand experience: a transplant recipient's story. AB - I received that wanted, needed, and feared telephone call. I wanted it for the freedom and hope it might bring. I needed it because of bone disease and fatigue. I feared it because of the surgery, possible complications, and the possibility of the most damning word for any transplant patient--rejection. PMID- 8506089 TI - Cardiac transplantation in New Jersey. AB - Heart transplantation is an effective treatment for end-stage congestive heart failure resulting in a one-year survival of 80 percent and a return to normal function in 90 percent of survivors. Refinements in the pre- and postoperative medical management of transplant recipients portend further benefits. PMID- 8506090 TI - Update on renal transplantation. AB - Renal transplantation has evolved as a preferred mode of long-term therapy for a substantial percentage of chronic renal failure patients. The author reviews recent progress in the field with an emphasis on patient counseling and with the conclusion that the outlook for these patients is bright. PMID- 8506091 TI - The demand for pancreatic transplantation in New Jersey. AB - Simultaneous kidney and pancreas transplantation is the accepted method of treatment in a selected group of type I diabetics with end-stage renal disease. In New Jersey, approximately 60 patients per year fall into this category and the number of patients is expected to increase rapidly. PMID- 8506092 TI - Infectious complications of bone marrow transplantation. AB - Patients undergoing bone marrow transplantation face increased risk of infection because of underlying diseases and transplant-associated treatments. Optimal prophylactic strategies and prompt recognition and treatment of infection are crucial. PMID- 8506093 TI - Bone marrow transplantation for the treatment of refractory malignancies. AB - Bone marrow transplantation has been employed with increasing frequency for patients with a variety of malignant disorders. Autologous bone marrow rescue (ABMR) is one of the most exciting and promising areas in clinical oncology. PMID- 8506094 TI - The first 50 liver transplants in New Jersey. AB - New Jersey's first liver transplant was performed on February 14, 1989, at UMDNJ New Jersey Medical School. By May 1992, 50 patients, ranging in age from 16 to 65 years, had been transplanted. Liver transplantation is an accepted method of treatment for end-stage liver disease. PMID- 8506095 TI - Lung transplantation in New Jersey. AB - Single- or bilateral-lung transplantation is an effective treatment for end-stage pulmonary diseases. Refinements in the surgical technique and postoperative management of recipients have resulted in a return to normal function in most cases and a one-year survival in 70 percent of patients. PMID- 8506096 TI - Common infections complicating lung transplantation. AB - Infections are the most common cause of early and late morbidity and mortality in lung transplant recipients. Viral infections, in particular, have been linked to acute rejection, chronic rejection, and development of lymphoproliferative diseases. PMID- 8506097 TI - Nutritional consideration for patients with organ transplants. AB - The immune response of the recipient and the therapeutics of immunomodulation significantly alter the relationship between allograft function and the composition and quantity of substrate. Successful management of nutrition along with post-transplant complications and drug therapy is of critical importance. PMID- 8506098 TI - A social worker's role on a transplant team. AB - Transplant team social workers are essential components of the team because of their knowledge and intervention skills in assisting patients. Sensitivity to the needs of the transplant patient is a catalyst for the development of creative intervention strategies. PMID- 8506099 TI - Organ donation: breaking down barriers. AB - From the perspective of the organ procurement organization, breaking down the barriers to organ donation may be the most important challenge facing transplant medicine today. Physicians will play a key role in the discussions concerning organ donation and transplantation. PMID- 8506100 TI - Immunosuppression: tomorrow and beyond. AB - Balancing the benefits and side effects of immunosuppressive therapy is important in transplant patients. Several new agents appear to be safer, more effective, and more specific than the available standard immunosuppressive drugs. Many of the agents are likely to be used with present drugs. PMID- 8506101 TI - Immediate breast reconstruction after mastectomy. AB - Immediate breast reconstruction after mastectomy can be performed safely with a low incidence of complications. There is no evidence that reconstruction with a submuscular implant interferes with subsequent oncologic care, followup, or outcome for patients. PMID- 8506102 TI - Early emergent coronary bypass after failed angioplasty. AB - Emergency CABG for failed coronary angioplasty was required in 3.3 percent of 1,625 consecutive patients undergoing angioplasties. Twenty-six percent of the patients died in the perioperative period. Efforts must be concentrated on identifying PTCA failure prior to cardiogenic shock. PMID- 8506104 TI - MRI and CT features of polycystic liver disease. AB - The authors report two cases of polycystic liver (PCL) disease with no other organ involvement. PCL, an uncommon disease that usually is asymptomatic, was diagnosed using computed tomography for one patient and magnetic resonance imaging for the other patient. PMID- 8506103 TI - Medical history: the Neer and Alexander years. AB - Many fine physicians have practiced in the Pascack Valley, but for sheer continuity of quality medical care and community service, the trio of Dr. Neer, Dr. Samuel Alexander, and Dr. Stewart Alexander, was extraordinary. Their careers can be summed up as professionalism with a face and with a heart. PMID- 8506106 TI - Mandatory AIDS testing could create hospital staffing problems. PMID- 8506105 TI - Infectious disease rounds: pneumonia due to Aspergillus. AB - Angioinvasive fungi, like Aspergillus, can cause invasive infections in patients immunosuppressed by steroid therapy. Pulmonary infarction, manifested as pleuritic chest pain, frequently results from in situ thrombosis and is characteristic of Aspergillus pneumonia. PMID- 8506108 TI - [Snoring and obstructive sleep apnea in childhood]. AB - In this paper the development of the diagnostic procedure of sleep apnoe syndrome is summarized and a survey of the pathophysiology and possible causes of this illness is given as well as two groups of patients children with hypertrophic tonsils and adenoids and tightenings after pharyngo-plastic operations where this disorder was observed are demonstrated. Detailed description is given of the examinations used as well as of the possibilities of treatment. PMID- 8506107 TI - [Breast-preserving operations in surgically treatable breast cancer]. AB - Since 1980, based on international experience, breast conserving operations have been introduced at the Surgical Department, in the National Oncological Institute, Budapest. In 12 years, out of 4622 primary breast cancer operations, 1055 breast preserving interventions were carried out. For all patients adjuvant radiotherapy was indicated. In lymph node positive premenopausal cases chemo radio-chemotherapy, for postmenopausal patients radiotherapy with tamoxifen has been provided. The first 604 patients (10 years) have been evaluated and 489 of them could be followed. The mean follow-up time was 49 months. During this period of time metastases have developed in 61 patients (12.5%); 26 (5.3%) of them died with the disease. Local recurrences occurred in 29 patients (5.9%). For small recurrences reexcision, for the others mastectomy or/and radiotherapy was carried out. Critical evaluation of the local recurrences was done. PMID- 8506109 TI - [Variability of the circadian heart rate in diabetes mellitus-related autonomic neuropathy]. AB - For assessing the alterations of circadian heart rate variability 66 diabetic patients (age: 52.9 +/- 1.0 years; x +/- SEM) and 23 control subjects (age: 52.7 +/- 1.7 years) were investigated using 24 hours Holter monitoring. Autonomic neuropathy (AN) was evaluated by tests for cardiovascular reflexes and patients were classified as being without AN (n = 26), having mild (n = 25) or definitive (n = 15) signs of AN. Minimal heart rates were significantly higher while maximal heart rates were considerably lower in patients with than without AN (60 +/- 2 min-1 versus 54 +/- 1, min-1, p < 0.05 and 125 +/- 4 min-1 versus 146 +/- 4 min 1, p < 0.01). Diabetic groups were comparable regarding values of averaged heart rates. The difference between the mean waking and sleeping averaged heart rates was the smallest in diabetic patients with definitive signs of AN (9 +/- 2 min-1) differing from those of control subjects (17 +/- 1 min-1, p < 0.01) and diabetic patients without (17 +/- 1 min-1, p < 0.001) or with mild (15 +/- 1 min-1, p < 0.05) signs of AN. Characteristic alteration, i.e. a reduction in circadian heart rate variability could be found in diabetic patients with signs of AN. This phenomenon has primarily been a consequence of more frequent sleeping heart rates due to dominant impairment in cardiac parasympathetic innervation. PMID- 8506110 TI - [Budapest physicians practicing alternative medicine (based on a September 1991 survey)]. AB - Our essay is the first attempt to raise the problems related to the Hungarian alternative medicine and to outline the tendencies in this field. In our research we tried to find answers to the following questions: 1. whether the physicians in disadvantageous position show a greater tendency to start dealing with alternative medicine, in order to make up for their low income; 2. to what extent can the appearance of the alternative practitioners on the market be regarded as a practice aimed merely at acquiring the maximum income; 3. we wanted to know the opinion of the physicians in connection with the regulation of alternative medicine, and 4. whether the cast of mind interiorized at the university can place the physicians into a disadvantageous position, as contrasted to those alternative practitioners who do not possess a university degree, because the physicians, just owing to the assumption of specific values, may be ousted from certain areas of the market. Twenty-eight alternative practitioners having physician certificate were interviewed, all of them being residents in Budapest, by means of telephone conversations. Owing to the small number of the questioned persons, our results represent merely the tendencies. Based on the acquired data, a negative answer must be given to the first question: that means, at the time of conducting the survey, alternative medicine can not be regarded as a form of finding a way out for the physicians in disadvantageous position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506111 TI - [Simultaneous surgery for trivalvular and ischemic heart disease as well as calcification of the ascending aorta]. AB - Authors present a case report about the surgical management of trivalvular and ischemic heart disease. The strategy of surgery: venous, arterial revascularisation, valve replacements, valvular plasty is discussed in conjunction with the management of the calcified ascending aorta. The details of the procedure and data of the early follow up period (6 months) are presented. PMID- 8506112 TI - [Miklos Szontagh (1843-1899) pioneer of climatotherapy]. PMID- 8506113 TI - [Data on the history of the management of diabetic coma. Thoughts on a 36-year old controversy]. PMID- 8506114 TI - The immunogenicity of hookworm (Necator americanus) acetylcholinesterase (AChE) in man. AB - A number of different but complementary approaches have been used to demonstrate the immunogenicity of Necator americanus acetylcholinesterase to infected individuals. Western blotting of parasite somatic extracts with human post infection sera and a specific rabbit antiserum to AChE resulted in the development of almost identical antigen-recognition profiles. AChE-containing fractions produced by preparative iso-electric focusing were subsequently shown to be antigenic in ELISA using post-infection sera. This preliminary data was reinforced by the affinity purification of AChE by immobilized post-infection IgG, and the immunoprecipitation of AChE activity from ES by post-infection IgG. Finally, AChE purified by affinity chromatography on edrophonium chloride was shown to be antigenic by Western blotting, and in ELISA, against post-infection sera, although a degree of re-activity was also seen with normal human sera. This data is discussed in the context of the host-parasite relationship. PMID- 8506115 TI - Soluble (s)CD23 levels in a parasitized population from Papua New Guinea. AB - Levels of sCD23, total and specific IgE were found to be considerably elevated in the plasma of a helminth infected population from Papua New Guinea. Using age corrected data, a significant negative correlation was seen between sCD23 and total IgE in the young, at a time when hookworms are being rapidly acquired, and total IgE levels are rising most dramatically. It is suggested on the basis of this data that this inverse correlation is due to the stabilizing effect of IgE on the Fc epsilon RII receptor in vivo, and that the high levels of sCD23 seen in hookworm infected individuals are partly responsible for the high levels of IgE recorded in these patients. PMID- 8506116 TI - Protective immunity and mast cell and eosinophil responses in mice infested with larval Haemaphysalis longicornis ticks. AB - WBB6F1-+/+ mice were infested with larval Haemaphysalis longicornis ticks twice at an interval of 14 days: apparent resistance against ticks was expressed in the second infestation. The first infestation induced degranulation of a small number of mast cells at the feeding sites within 6 days, and resulted in two-fold increases of mast cell numbers on day 14 with a significant elevation of total immunoglobulin E (IgE) levels in sera and high proportion of IgE-bound mast cells. The second infestation resulted in the intensive degranulation of the increased mast cells at the feeding sites. Eosinophils infiltrated into the feeding sites of ticks: the second infestation led to a greater maximal level of the infiltrating eosinophils. These data suggest that the resistance against larval H. longicornis ticks in mice may be expressed as a result of immediate hypersensitivity and many eosinophils infiltrating from the blood to the feeding sites might contribute to the tick rejection. PMID- 8506117 TI - Host genetics and resistance to acute Trypanosoma cruzi infection in mice. I. Antibody isotype profiles. AB - Some strains of inbred mice survive acute infection with Trypanosoma cruzi while others die within a few weeks after infection. Mice which express B10 background genes and either the H-2q or H-2d haplotypes are resistant and survive. However, mice which share the B10 genetic background but express H-2k alleles die, usually within 4 weeks following infection. These data confirm that at least 1 gene in the major histocompatibility complex can determine whether an animal lives or dies during the acute phase. Expression of the H-2q haplotype on the B10 genetic background or in DBA/1 mice is associated with resistance, but H-2q mice expressing the C3H background are susceptible. Therefore, at least 1 gene in the genetic background also influences resistance. Our data suggest that genes associated with resistance must be present in both the MHC and the genetic background or the animal will die. The isotypes and specificities of parasite reactive antibodies found in the serum of different inbred mouse strains were assessed during acute infection. Levels of IgM were higher in sera from mice which express the resistant B10 background than in sera from mice expressing the susceptible C3H background. Conversely, mice which share the C3H background genes produced high levels of anti-parasite IgG2a when compared to B10 congenic strains. Antigen specificity, however, may be influenced by both background and MHC genes, as congenic strains expressing different MHC haplotypes recognized different constellations of T. cruzi antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506118 TI - Induction of complement resistance in cloned pathogenic Entamoeba histolytica. AB - The lytic effect of complement activated through the alternative pathway (AP) was studied on pathogenic and nonpathogenic Entamoeba histolytica recently isolated from stool samples. Recent nonpathogenic isolates were nearly unaffected by exposure to AP whereas recent pathogenic stool isolates were highly susceptible to AP dependent complement-mediated lysis. Complement susceptible pathogenic stool isolates developed complement resistance in vivo during hamster liver passage and in vitro during cultivation in the presence of increasing concentrations of normal human serum (NHS). Since a clone of pathogenic HM-1:IMSS which initially was highly susceptible also acquired complement resistance during cultivation in the presence of NHS, it is concluded that complement resistance was caused by induction rather than by selection alone. Because cultivation in the presence of heat-inactivated NHS did not affect complement susceptibility of the cloned HM-1:IMSS, complement activation itself might induce complement resistance in pathogenic E. histolytica. PMID- 8506120 TI - With new eyes: the animal rights movement and religion. PMID- 8506119 TI - Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum. AB - P. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP 1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component. PMID- 8506121 TI - The history of steroidal contraceptive development: the progestins. PMID- 8506122 TI - The history of steroidal contraceptive development: the estrogens. PMID- 8506123 TI - Physicians and the pharmaceutical industry: an alliance with unhealthy aspects. PMID- 8506124 TI - Nonconventional genetic systems. PMID- 8506125 TI - Unexpected substrate specificity of T4 DNA ligase revealed by in vitro selection. AB - We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 DNA ligase. We find that the ensemble of selected sequences ligates about 50 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly many of the selected sequences failed to produce a match at or close to the ligation junction. None of the 20 selected oligomers that we sequenced produced a match two bases upstream from the ligation junction. PMID- 8506126 TI - The adenovirus terminal protein influences binding of replication proteins and changes the origin structure. AB - The adenovirus terminal protein (TP) is covalently linked to the 5' ends of the adenovirus genome and enhances DNA replication in vitro by increasing template activity. To study the effect of TP in more detail we isolated short origin fragments containing functional TP using anion exchange chromatography. These fragments were highly active as templates for DNA replication in a reconstituted system. Employing band-shift assays we found that the affinity of the precursor terminal protein-DNA polymerase complex for the TP-containing origin was increased 2 to 3-fold. Binding affinities of two other replication stimulating proteins, NFI and Oct-1, were not influenced by the terminal protein. Upon DNaseI footprinting we observed, unexpectedly, that the breakdown pattern had changed at various positions in the origin, notably in the area 3-6 and 41-51 by the presence of TP. Some differences in the footprint pattern of NFI and Oct-1 were also found. Our results indicate that TP induces subtle changes in the origin structure that influence the interaction of other replication proteins. PMID- 8506127 TI - Interaction of proteins with the mRNA for ribosomal protein L1 in Xenopus: structural characterization of in vivo complexes and identification of proteins that bind in vitro to its 5'UTR. AB - Xenopus r-protein mRNAs are known to be coordinately regulated at the translational level. To find out if RNA/protein interactions are involved in this control mechanism, we have characterized the particles containing the translationally repressed rp-mRNA and we have investigated the proteins that specifically bind to this type of mRNA. By sedimentation analysis and isopycnic centrifugation we have found that the repressed rp-mRNAs are assembled in slow sedimenting complexes where the RNA is prevalent over the protein mass (2.3 to 1). This composition is maintained also after in vitro reconstitution of the particle. We carried out also a detailed analysis of in vitro RNA/protein complex formation by focusing our attention on the 5'UTR, very similar in different rp mRNAs and important in the translational regulation. We describe specific interactions of L1 mRNA with four proteins. The binding site of two of them, 57 kD and 47 kD, is in the typical pyrimidine sequence at the 5' end and is position dependent. Proteins of the same size interact also with the analogous region of r protein S1 and L14 mRNA, not with unrelated RNAs. Binding of two other proteins, 31 kD and 24 kD, in the downstream region of the 5'UTR was also observed. The most evident 57 kD protein has been partially purified. Although the binding of these proteins to the r-protein mRNA 5'UTR is specific, their involvement in the translation regulation remains to be proved. PMID- 8506128 TI - Gene structure and expression of the MboI restriction--modification system. AB - The genes from Moraxella bovis encoding the MboI restriction--modification system were cloned and expressed in Escherichia coli. Three open reading frames were found in the sequence containing the genes. These genes, which we named mboA, mboB, and mboC, had the same orientation in the genome. Genes mboA and mboC encoded MboI methyltransferases (named M.MboA and M.MboC) with 294 and 273 amino acid residues, respectively. The mboB gene coded for MboI restriction endonuclease (R.MboI) with 280 amino acid residues. Recombinant E.coli-MBOI, which contained the whole MboI system, overproduced R.MboI. R.MboI activity from E.coli-MBOI was 480-fold that of M.bovis. The amino acid sequences deduced from these genes were compared with those of other restriction--modification systems. The protein sequences of the MboI system had 38-49% homology with those of the DpnII system. PMID- 8506129 TI - Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression. AB - Comparison of nucleotide sequences from different classes of vertebrates that diverged more than 300 million years ago, revealed the existence of highly conserved regions (HCRs) with more than 70% similarity over 100 to 1450 nt in non coding parts of genes. Such a conservation is unexpected because it is much longer and stronger than what is necessary for specifying the binding of a regulatory protein. HCRs are relatively frequent, particularly in genes that are essential to cell life. In multigene families, conserved regions are specific of each isotype and are probably involved in the control of their specific pattern of expression. Studying HCRs distribution within genes showed that functional constraints are generally much stronger in 3'-non-coding regions than in promoters or introns. The 3'-HCRs are particularly A + T-rich and are always located in the transcribed untranslated regions of genes, which suggests that they are involved in post-transcriptional processes. However, current knowledge of mechanisms that regulate mRNA export, localisation, translation, or degradation is not sufficient to explain the strong functional constraints that we have characterised. PMID- 8506130 TI - Chromatin structures and transcription of rDNA in yeast Saccharomyces cerevisiae. AB - The chromatin structure of yeast ribosomal DNA was analyzed in vivo by crosslinking intact cells with psoralen. We found that in exponentially growing cultures the regions coding for the 35S rRNA precursor fall into two distinct classes. One class was highly accessible to psoralen and associated with nascent RNAs, characteristic for transcriptionally active rRNA genes devoid of nucleosomes, whereas the other class showed a crosslinking pattern indistinguishable from that of bulk chromatin and was interpreted to represent the inactive rRNA gene copies. By crosslinking the same strain growing in complex or minimal medium, we have shown that yeast cells can modulate the proportion of active (non-nucleosomal) and inactive (nucleosomal) rRNA gene copies in response to variations in environmental conditions which suggests that yeast can regulate rRNA synthesis by varying the number of active gene copies, in contrast to the vertebrate cells studied so far. Whereas intergenic spacers flanking inactive rRNA gene copies are packaged in a regular nucleosomal array, spacers flanking active genes show an unusual crosslinking pattern suggesting a complex interaction of regulatory factors and histones with DNA. PMID- 8506131 TI - Probing DNA-protein interactions in vitro with the CpG DNA methyltransferase. AB - A sensitive method was devised to monitor the in vitro binding of nuclear proteins from HeLa cells presumably to the major groove of DNA. Upon the incubation of DNA with nuclear extracts, the complexed DNA was incubated with the CpG DNA methyltransferase from Spiroplasma species. Subsequently, the DNA was repurified, and the location of the methylated cytidine residues was determined by the hydrazine reaction of the DNA sequencing method. By using as DNA substrate the VAI (virus associated) region of human adenovirus type 2 (Ad2) DNA or specific Alu sequences associated with a number of human genes, it was documented that those segments of DNA that were protected by bound proteins against the reaction with DNasel also escaped in vitro methylation by the CpG DNA methyltransferase. This new footprinting method provides a sensitive indicator for in vitro DNA--protein interactions which are specific for the major groove of DNA. PMID- 8506132 TI - Energetics of Z-DNA formation in poly d(A-T), poly d(G-C), and poly d(A-C) poly d(G-T). AB - The conformational change for the alternating purine-pyrimidine polydeoxyribonucleotides i.e. poly d(A-T), poly d(G-C), and poly d(A-C) poly d(G T) from a right-handed conformation at room temperature to the left-handed Z-DNA like double helix at elevated temperatures has been studied by UV spectroscopy, Raman spectroscopy, and by adiabatic differential scanning microcalorimetry (DSC) in the presence of Na+ and Mg2+ or Ni2+ respectively as counterions. The differential UV spectra reveal through a hyperchromic shift at around 280nm and a hypochromic shift at 260nm that a conformational change to the left-handed conformation occurs. The Raman spectra clearly show characteristic changes, a drastic decrease of the band at 680cm-1 and the appearance of a new band at 628cm 1, due to the change of the purine bases to the syn conformation upon inversion of the helix-handedness. The course of the transition as function of temperature can be followed quantitatively by plotting the change in the excess heat capacity vs. temperature. The transition enthalpy delta H for the B- to Z-DNA transition per mole base pairs (mbp) amounts to 2.0 +/- 0.2kcal for poly d(G-C), to 4.0 +/- 0.4kcal for poly d(A-T), and to 3.1 +/- 0.3kcal for poly d(A-C) poly d(G-T). The enthalpy change due to the Z-DNA to coil transitions (per mole base pairs) amounts to 11kcal for poly d(G-C), 10.5kcal for poly d(A-T) and 11.3kcal for poly d(A-C) poly d(G-T). PMID- 8506133 TI - DNA sequence determinants of LexA-induced DNA bending. AB - The LexA repressor from Escherichia coli induces DNA bending upon interaction with the two overlapping operators which regulate the transcription of the colicin A encoding gene caa. Both caa operators harbor T-tracts adjacent to their recognition motifs. These tracts have been suggested to be especially favorable for the promotion of LexA-induced DNA bending. Here we show that this is indeed the case, since disruption of the TTTT-tract adjacent to operator O1 by the replacement of the two central thymine bases by AA, GA or CG markedly reduces LexA-induced DNA bending. Simple A.T-richness in this position is thus not sufficient to promote full LexA-induced bending, albeit a TAAT sequence is always more efficient to promote bending than those sequences containing one or two C/G base pairs. PMID- 8506134 TI - The determination of the sequences present in the shadow bands of a dinucleotide repeat PCR. AB - A Polymerase Chain Reaction (PCR) of a DNA sequence containing a CA repeat produces a main band but also several shadow bands that differ by 2 base pairs below the main band. In the experiments described in this paper, these shadow bands were excised from a DNA sequencing gel and directly sequenced. It was found that the sequence in the CA repeat was ambiguous. However, the sequence 5' and 3' to the CA repeat was clear and unambiguous. It is proposed that the shadow bands are generated by 2 base pair random deletions in the CA repeat region. During this process the sequence becomes 'scrambled' only in the CA repeat region. The shadow bands were shown to occur during the PCR since the genomic DNA template did not contain the shadow bands. It is probable that the shadow bands arise by slippage during the PCR. It is predicted that a thermostable DNA polymerase with a high processivity would greatly reduce the occurrence of shadow bands. PMID- 8506136 TI - A micronucleus-specific sequence exists in the 5'-upstream region of calmodulin gene in Tetrahymena thermophila. AB - Tetrahymena thermophila possesses a transcriptionally inactive micronucleus and an active macronucleus. Both nuclei are developed from micronucleus-derived germ nuclei during conjugation. Extensive DNA rearrangement and transcriptional activation are known to be involved in macronuclear development, but little has been known about these processes in a particular functional gene. Therefore the micro- and macronuclear genomic DNAs for calmodulin gene were analyzed. A 1,384 bp micronucleus-specific sequence located about 3.5 kb upstream of calmodulin gene has been found, suggesting DNA rearrangement during macronuclear development. The micronucleus-specific sequence had 85% A + T, no extensive ORF, ATTAs at both ends, and two palindromic structures just outside of both ends. Interestingly, the micronucleus-specific sequence included a T-rich tract, T16CT5, in the middle, and a nearly complementary A-rich tract, A5TA10GA5, existed 7 bp upstream from the initiation codon. In addition, there was a 20 bp repetitive sequence TAAT(TAAC)4 about 100 bp upstream of the micronucleus specific sequence and also in the promoter region of calmodulin gene. Although the functional significance of the micronucleus-specific sequence remains unclear, T16CT5 and TAAT(TAAC)4 elements might exert an influence on transcription of the calmodulin gene. Stringent Southern hybridization revealed that this micronucleus-specific sequence or very similar sequence(s) were abundant in the Tetrahymena micronuclear genome. PMID- 8506135 TI - Retrovirus-mediated insertion of expressed and non-expressed genes at identical chromosomal locations. AB - During retrovirus replication, a cellularly derived tRNA is annealed to the viral RNA at the primer binding site (PBS) to prime reverse transcription, and both the tRNA and the PBS become copied and matched together on complementary proviral DNA strands prior to integration. Using a viral PBS single base pair mutant which affects provirus expression in undifferentiated cells, we show that reversion to wild type (wt) occurs at a frequency of approximately 50%. Daughter cell lines containing wt or mutant proviruses at identical chromosomal sites have been isolated, supporting a model where an integrated PBS-mismatched provirus was copied before mismatch correction could occur. Virus expression in daughter cells containing the mutant provirus was 100-fold higher than in cells bearing the wt counterpart. Additionally, proviral 5' DNA and cellular 5' flanking DNA became methylated in daughter cells containing wt but not mutant integrants. These results strongly support the current model of retrovirus reverse transcription, and indicate that the wt PBS region contains an element which suppresses virus expression and directs the methylation of viral and neighboring cellular DNA. PMID- 8506137 TI - Variation and in vitro splicing of group I introns in rRNA genes of Pneumocystis carinii. AB - The sequences of the rRNA genes of Pneumocystis carinii from rat and human sources demonstrate three distinct genotypes based on the group I introns present in these genes. One rat isolate (Pc1) contains such introns in its 16S and 26S rRNA genes, while another rat isolate (Pc2) and a human isolate (Pc3) only contain an intron in the 26S rRNA gene. The four introns all catalyze their own excision from RNA transcripts, and this reaction is inhibited by the anti pneumocystis drug pentamidine and its analogues. Although they differ in sequence, they are more similar to one another than to group I introns found in other eukaryotic microbes. PMID- 8506139 TI - In vivo UV-cross-linking hybridization: a powerful technique for isolating RNA binding proteins. Application to trypanosome mini-exon derived RNA. AB - Differential gene expression in cells achieved, in part, through direct RNA protein interactions. Methods for the identification of RNA binding proteins require cross-linking of proteins to RNA by chemicals or ultraviolet (UV) light followed by chromatography or density-gradient centrifugation (7,11,16). We have developed a simplified method for the rapid and efficient identification of potential regulatory RNA binding proteins. In this method, irradiation of cells with UV light induces cross-links between RNA and proteins in close contact (7,11). Boiling of extracts from irradiated cells in the presence of sodium dodecyl sulfate dissociates any non-specific RNA-protein interactions (11). After analysis of the cell extracts by SDS-PAGE, followed by Western blotting onto a nitrocellulose membrane and washing of the filter, we have found that only RNA molecules that are covalently bound to proteins are retained on the filter. Hybridization of this Western blot with an appropriate nucleic acid probe allows detection of bands of RNA-protein complexes. Antisera against the binding proteins are raised by immunizing mice with a region of the nitrocellulose membrane containing the bands of RNA-protein complexes. Using this approach we have found that in African trypanosomes, mini-exon derived RNA transcripts form complexes with cytoplasmic binding proteins in different life cycle stages of the parasite. Evidence for the specificity of mini-exon derived RNA-protein interactions is shown using in vitro UV-cross-linking analysis in which only in vitro generated sense (but not antisense) mini-exon derived RNA transcripts form complexes with cytoplasmic proteins. PMID- 8506138 TI - African swine fever virus encodes two genes which share significant homology with the two largest subunits of DNA-dependent RNA polymerases. AB - A random sequencing strategy applied to two large SalI restriction fragments (SB and SD) of the African swine fever virus (ASFV) genome revealed that they might encode proteins similar to the two largest RNA polymerase subunits of eukaryotes, poxviruses and Escherichia coli. After further mapping by dot-blot hybridization, two large open reading frames (ORFs) were completely sequenced. The first ORF (NP1450L) encodes a protein of 1450 amino acids with extensive similarity to the largest subunit of RNA polymerases. The second one (EP1242L) codes for a protein of 1242 amino acids similar to the second largest RNA polymerase subunit. Proteins NP1450L and EP1242L are more similar to the corresponding subunits of eukaryotic RNA polymerase II than to those of vaccinia virus, the prototype poxvirus, which shares many functional characteristics with ASFV. ORFs NP1450L and EP1242L are mainly expressed late in ASFV infection, after the onset of DNA replication. PMID- 8506140 TI - The DNA binding affinity of HhaI methylase is increased by a single amino acid substitution in the catalytic center. AB - The HhaI methyltransferase recognizes the sequence GCGC and transfers a methyl group to C5 of the first cytosine residue. All m5C-methyltransferases contain a highly conserved sequence motif called the P-C motif. The cysteine residue of this motif is involved in catalysis by forming a covalent bond with the 6 position of cytosine prior to methyl group transfer. For the EcoRII methyltransferase, it has been shown that substitution of this catalytic cysteine by glycine is cytotoxic to E.coli cells expressing the mutant methyltransferase (Wyszynski et al. Nucl. Acids Res. 20: 319, 1992). We now show that this observation can be extended to the HhaI system and suggest that the cytotoxicity is due to abnormally tight DNA binding by the mutant methyltransferase, which probably interferes with replication or transcription. PMID- 8506141 TI - Modified nucleotides in Bacillus subtilis tRNA(Trp) hyperexpressed in Escherichia coli. AB - In the present study, modified nucleotides in the B. subtilis tRNA(Trp) cloned and hyperexpressed in E. coli have been identified by TLC and HPLC analyses. The modification patterns of the two isoacceptors of cloned B. subtilis tRNA(Trp) have been compared with those of native tRNA(Trp) from B. subtilis and from E. coli. The modifications of the A73 mutant of B. subtilis tRNA(Trp), which is inactive toward its cognate TrpRS, were also investigated. The results indicate the formation of the modified nucleotides S4U8, Gm18, D20, Cm32, i6A/ms2i6A37, T54 and psi 55 on cloned B. subtilis tRNA(Trp). This modification pattern resembles the pattern of E. coli tRNA(Trp), except that m7G is missing from the cloned tRNA(Trp), probably on account of its short extra loop. In contrast, the pattern departs substantially from that of native B. subtilis tRNA(Trp). Therefore, the cloned B. subtilis tRNA(Trp) has taken on largely the modification pattern of E. coli tRNA(Trp) despite the 26% sequence difference between the two species of tRNA, gaining in particular the Cm32 and Gm18 modifications from the E. coli host. A notable difference between the isoacceptors of the cloned tRNA(Trp) was seen in the extent of modification of A37, which occurred as either the hypomodified i6A or the hypermodified ms2i6A form. Surprisingly, base substitution of guanosine by adenosine at position 73 of the cloned tRNA(Trp) has led to the abolition of the 2'-O-methylation modification of the remote G18 residue. PMID- 8506142 TI - Nucleotide, dinucleotide and trinucleotide frequencies explain patterns observed in chaos game representations of DNA sequences. AB - The chaos game representation (CGR) is a scatter plot derived from a DNA sequence, with each point of the plot corresponding to one base of the sequence. If the DNA sequence were a random collection of bases, the CGR would be a uniformly filled square; conversely, any patterns visible in the CGR represent some pattern (information) in the DNA sequence. In this paper, patterns previously observed in a variety of DNA sequences are explained solely in terms of nucleotide, dinucleotide and trinucleotide frequencies. PMID- 8506144 TI - Sequence and proposed secondary structure of the Tetrahymena thermophila U3 snRNA. PMID- 8506143 TI - Ancestry and diversity of the HMG box superfamily. AB - The HMG box is a novel type of DNA-binding domain found in a diverse group of proteins. The HMG box superfamily comprises a.o. the High Mobility Group proteins HMG1 and HMG2, the nucleolar transcription factor UBF, the lymphoid transcription factors TCF-1 and LEF-1, the fungal mating-type genes mat-Mc and MATA1, and the mammalian sex-determining gene SRY. The superfamily dates back to at least 1,000 million years ago, as its members appear in animals, plants and yeast. Alignment of all known HMG boxes defined an unusually loose consensus sequence. We constructed phylogenetic trees connecting the members of the HMG box superfamily in order to understand their evolution. This analysis led us to distinguish two subfamilies: one comprising proteins with a single sequence-specific HMG box, the other encompassing relatively non sequence-specific DNA-binding proteins with multiple HMG boxes. By studying the extent of diversification of the superfamily, we found that the speed of evolution was very different within the various groups of HMG-box containing factors. Comparison of the evolution of the two boxes of ABF2 and of mtTF1 implied different diversification models for these two proteins. Finally, we provide a tree for the highly complex group of SRY-like ('Sox' genes), clustering at least 40 different loci that rapidly diverged in various animal lineages. PMID- 8506145 TI - Streptomyces aureofaciens whiB gene encoding putative transcription factor essential for differentiation. PMID- 8506146 TI - BSP1407I, a restriction endonuclease from Bacillus stearothermophilus, which recognizes novel palindromic sequence 5'-T decreases GTACA-3'. PMID- 8506147 TI - A possible mechanism for metal-ion induced DNA-protein dissociation in a family of prokaryotic transcriptional regulators. PMID- 8506148 TI - Nucleotide sequence of three tRNA genes from tomato chloroplast genome. PMID- 8506149 TI - RNase T shares conserved sequence motifs with DNA proofreading exonucleases. PMID- 8506150 TI - Identification of a Drosophila protein similar to rat S13 and archaebacterial S11 ribosomal proteins. PMID- 8506151 TI - Nucleotide sequence of the genes encoding L11 and L1 equivalent ribosomal protein from Streptomyces sp. FRI-5. PMID- 8506152 TI - Rapid sequencing of rDNA from single worms and eggs of parasitic helminths. PMID- 8506153 TI - PCR amplification from single seeds, facilitating DNA marker-assisted breeding. PMID- 8506154 TI - Chopped inserts: a convenient alternative to agarose/DNA inserts or beads. PMID- 8506155 TI - A rapid and gentle method for the isolation of genomic DNA from mycobacteria. PMID- 8506156 TI - Distinguishing specific from nonspecific complexes on southwestern blots by a rapid DMS protection assay. PMID- 8506157 TI - Determination of the molecular mass of the transcription factor interacting with FBS2 in c-fos promoter. PMID- 8506159 TI - An editor for all seasons. PMID- 8506160 TI - An exploration of Pender's Health Promotion Model using LISREL. AB - A causal model based on Pender's (1987) Health Promotion Model was tested to evaluate Pender's hypothesis that demographic and biological characteristics affect health-promoting behaviors indirectly through three mediating cognitive perceptual variables. A sample of 3,025 noninstitutionalized adults completed a telephone survey from which indicators of the conceptual variables were selected. Initial tests of the causal model using the LISREL 7 program indicated that the basic model did not fit the data. Therefore, the model was modified so that the exogenous variables--sex, age, income, martial status, education, and body mass index--had direct effects on select health-promoting behaviors. Further, the variables of self-actualization and interpersonal support were required to share common indicators as were health responsibility and interpersonal support. Though the modified model fit the data, little of the variance in health-promoting behaviors was explained, since all significant effects were weak. PMID- 8506158 TI - DNA-mediated transformation of bloodstream-form Trypanosoma brucei. PMID- 8506161 TI - Instrument refinement for breast cancer screening behaviors. AB - The purpose of this study was to refine an instrument to measure the Health Belief Model concepts of susceptibility, seriousness, benefits, barriers, health motivation, and confidence, using the context of breast cancer and breast self examination. A Likert format was used for attitudinal scales. A random sample (N = 581) of women 35 years and over was included. Items were subjected to content analysis by national experts. Construct validity was established using exploratory factor analysis. Predictive validity was established by relating breast self-examination behavior to breast self-examination attitudes, using simultaneous multiple regression and bivariate correlations. Cronbach alpha reliability coefficients for the revised scales ranged from .80 to .93. Test retest correlations ranged from .45 to .70. PMID- 8506162 TI - Factor analysis of the Maternal Fetal Attachment Scale. AB - The purpose of this study was to assess the validity of the Maternal Fetal Attachment Scale (MFAS) subscales using factor analysis. The 23-item MFAS is composed of five subscales that have been used to represent the theorized dimensions of prenatal attachment. Two samples of MFAS scores were submitted to principal axis factoring with varimax rotation. The resulting solutions failed to correspond to the subscales of the MFAS and were also different from one another. These results indicate that the use of the MFAS subscales, as currently constructed, is problematic. PMID- 8506163 TI - Parental Stressor Scale: neonatal intensive care unit. AB - This article is a report of the development of the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU), which is designed to measure parental perception of stressors arising from the physical and psychosocial environment of the neonatal intensive care unit. Stress theory, literature reviews, expert consultation, and parent interviews guided instrument development and refinement and established the content validity of the instrument. Construct validity is supported by links with theory, correlation with anxiety measures, and factor analytic results. Alpha coefficients support the tool's internal consistency. Three scales were identified: Parental Role Alterations, Sights and Sounds of the Unit, and Infant Behavior and Appearance. Available metrics allow scoring for stress occurrence levels, overall stress levels, and number of stressors experienced. The PSS:NICU can serve as a research or clinical measure to evaluate stressors experienced by parents with infants in a NICU. PMID- 8506164 TI - Body image in women treated for breast cancer. AB - Body image, as a component of self-concept, was compared in four groups of women (N = 257) who received the most common types of treatment for breast cancer: mastectomy, mastectomy with delayed reconstruction, mastectomy with immediate reconstruction, and conservative surgery. Data were collected by mailed questionnaires using self-report instruments. Comparison of groups using analysis of covariance with age as a covariate indicated that mean body image in the conservative surgery group was significantly more positive than in either the mastectomy group or in the mastectomy with immediate reconstruction group. No differences in self-concept were evident among the four groups. PMID- 8506165 TI - Menstrual response to running: nursing implications. AB - Overt (length of menstrual cycle, duration of menses, and amount of menses) and covert (luteal surge indicative of ovulation and length of luteal phase) menstrual cycle characteristics were studied in a sample of 146 women who participated in four levels of running intensity. Menstrual and running data were collected for 4 months or 3 cycles. There was a significant difference among the four groups in duration of menses and in the amount of menses, with nonrunners having significantly more days of menses and larger amounts of menses than the two highest intensity running groups. However, when a history of skipping menstrual periods between menarche and age 18 was controlled, the differences between the groups were not significant. There were no significant differences among the four groups in incidence of luteal surge or length of luteal phase. When runners were compared to nonrunners, runners reported, on average, a shorter luteal phase than nonrunners. This difference remained when controlling for age and history of skipping menstrual periods. There was no significant difference between the four groups on incidence of ovulatory disturbances (anovulation or more than one cycle with a shortened luteal phase). But, when compared to nonrunners, runners were found to have significantly more ovulatory disturbances. The best predictors of the variance in menstrual cycle characteristics were history of skipping periods between menarche and age 18, and running versus nonrunning. PMID- 8506166 TI - Gender differences in exercise determinants. AB - To determine whether gender differences existed in the relationships among potential predictors of leisure-time physical activity (LTPA), a heuristic model of nine explanatory variables was tested with the responses of 146 men and 158 women randomly selected from middle- and upper-income census tracts of a midwestern city. The models for men and women did not differ significantly. The findings suggest interventions to increase LTPA participation that enhance health self-determinism and social influences on exercise and influence the negative attitudes toward exercise held by those who have poorer perceived health status, smoke, or are overweight. PMID- 8506167 TI - Physical and emotional abuse in pregnancy: a comparison of adult and teenage women. AB - A sample of 691 African American, Hispanic, and white pregnant teenage and adult women were interviewed in the prenatal setting. On their first prenatal visit, 182 (26%) women reported physical or sexual abuse within the past year. There were significant differences between the teens and adults, with a higher percentage of teens (31.6%) reporting abuse during the prior year than adults (23.6%). The rate of abuse during pregnancy was 21.7% for teens and 15.9% for adult women. Adult women scored significantly higher than teens on two measures of mental abuse. Mental abuse was significantly correlated with physical abuse for all subjects. PMID- 8506169 TI - Treating ordinal scales as ordinal scales. PMID- 8506168 TI - Factors related to graduate nursing faculty scholarly productivity. AB - Department-level measures of productivity were constructed using information reported by 180 nursing deans of schools with graduate (master's and doctoral) programs. Productivity was calculated three ways: total (net), publications, and grants. The scores for each school were derived from nine categories of faculty scholarly activities. The following variables were examined for their contribution to productivity: three measures of environmental support, budgeted and doctorally prepared faculty, students (master's, doctoral), all graduate students-faculty ratio, scholarship time, and private faculty offices. The regressions of log-transformed variables yielded R2 = .59 for total (net) productivity, .54 for publications, and .50 for grants productivity. PMID- 8506170 TI - Children's Bureau: guardian of American children. PMID- 8506171 TI - Basal cell carcinoma. Choosing the best method of treatment for a particular lesion. AB - Basal cell carcinoma is the most common type of malignant tumor in the United States. The five types of basal cell carcinoma (noduloulcerative, pigmented, morpheaform, and superficial basal cell carcinoma, and premalignant fibroepithelioma) vary in clinical presentation and behavior. Diagnosis is made by skin biopsy. The size, type, and site of a lesion and the age and sex of the patient affect the choice of treatment. Electrodesiccation and curettage, cryosurgery, surgical excision, Mohs' surgery, and radiation therapy are available. Knowledge of these therapies and of when they should and should not be used is important in proper management of basal cell carcinoma. PMID- 8506172 TI - Thrombosis in patients with cancer. AB - The relationship between cancer and abnormalities of blood coagulation has been recognized for well over a century. Deep venous thrombosis of the lower extremities is most common, but pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular coagulation, and other, more unusual, clinical events may occur. Chemotherapy also has been linked to thrombotic episodes. Anticoagulant therapy is appropriate in many patients with venous or arterial thrombosis. Prophylaxis of venous thrombosis is particularly important in hospitalized cancer patients who are at bed rest or undergoing surgery. PMID- 8506174 TI - Viral meningitis. Tips to rapidly diagnose treatable causes. AB - Viral meningitis is a common illness among children and is most often caused by enteroviruses. Diagnosis is made on the basis of clinical findings and analysis of the cerebrospinal fluid. Important conditions to consider in diagnosis are partially treated bacterial meningitis, tuberculous meningitis, fungal meningitis, other infections, and central nervous system tumor. Ruling out treatable causes early is important. Treatment of enteroviral meningitis is supportive, and the prognosis is usually very good, although significant neurologic sequelae have been reported. PMID- 8506173 TI - Arthropathy and HIV infection. A muddle of mimicry. AB - Several rheumatic diseases are associated with human immunodeficiency virus (HIV) infection. The most common are reactive and psoriatic arthritis. Classic septic arthritis caused by Staphylococcus aureus and other common organisms is very rare: Instead, infectious arthritis caused by unusual organisms is the rule. Some of the HIV-related rheumatic syndromes behave like classic rheumatic diseases, while others may actually be new forms of disease. Often, one of the rheumatic syndromes is the presenting manifestation of underlying HIV infection. HIV infected patients and patients with rheumatic disease often have similar laboratory abnormalities. Systemic lupus erythematosus, in particular, may be mistaken for HIV infection, in part because of cross-reactivity of antibodies. However, coexistence of systemic lupus erythematosus and rheumatoid arthritis with HIV infection is a rare occurrence. Traditional therapy for rheumatic diseases may not be indicated in HIV-infected patients and in fact may even be contraindicated. PMID- 8506175 TI - Antibiotics for nursing home residents. When are they appropriate? AB - Antibiotics are used often in nursing homes in response to high rates of infection. Physicians and nursing home administrators and staff need to work in concert to avoid inappropriate prescription of antibiotics in this setting. Physicians need to know how infection presents in frail, institutionalized elderly patients; strive to prevent infection; and prescribe antibiotics only in situations in which clear benefit has been demonstrated. Nursing home administrators and staff must institute comprehensive infection control programs, adopt specific guidelines for antibiotic use, and keep physicians informed about the number and types of infections and antibiotic susceptibility patterns. PMID- 8506176 TI - Allergy to insect stings. A need for improved preventive management. AB - Allergy to insect venom is a major health problem for a significant number of people. Immunotherapy can reduce the risk of subsequent reaction from about 60% to less than 5%. Standard preventive care should include (1) advice concerning avoidance of insects, (2) prescription of an epinephrine kit or syringe for self administration (unless medically contraindicated), and (3) referral for evaluation. Results of several studies from various regions of the country raise concern about the preventive care and advice given these patients and suggest a need for continuing medical education to improve preventive management of allergy to insect stings. PMID- 8506177 TI - It's you and me against our KGB! PMID- 8506178 TI - Aortoenteric fistulas. Recognizing a potentially catastrophic cause of gastrointestinal bleeding. AB - Aortoenteric fistulas are a relatively rare but serious cause of massive gastrointestinal hemorrhage. Most occur as a consequence of aortic reconstructive surgery and involve the proximal graft anastomosis. The distal duodenum is the site of bleeding in about three fourths of cases. Most patients have an initial episode of bleeding followed hours to weeks later by catastrophic hemorrhage. Patients with gastrointestinal bleeding who have undergone prior aortic reconstructive surgery should be approached with a great sense of urgency and a high index of suspicion. Endoscopic and radiographic studies can be very helpful, but the absence of abnormalities does not exclude the diagnosis. Exploratory laparotomy is indicated in patients with massive bleeding or those in whom results of other diagnostic studies have been normal. Treatment of aortoenteric fistula is early surgical intervention. Complete excision of the graft is preferred over patching or closing the defect. The mortality rate is essentially 100% without prompt surgical treatment. PMID- 8506179 TI - Cardiopulmonary resuscitation. New and controversial techniques. AB - Primary care physicians may need to perform cardiopulmonary resuscitation (CPR) from time to time. Knowledge regarding CPR has become extensive, and it is hoped that greater success will be achieved in the future with the advent of new methods. A number of techniques and devices have received attention in the lay and professional press. If appropriate care is to be delivered, practicing physicians must be aware of what is proven technology and what is investigational. PMID- 8506180 TI - Condoms and birth control in school clinics. PMID- 8506181 TI - Condoms and birth control in school clinics. PMID- 8506182 TI - Condoms and birth control in school clinics. PMID- 8506183 TI - Tips for treatment of ascariasis. PMID- 8506185 TI - Osteoporosis in men. Is it more common than we think? AB - Men are most at risk for hip fracture as they grow older because of age-related loss of bone in the femur. Men with low peak bone mass are more vulnerable than those who achieved a higher peak bone mass in early adulthood. Peak bone mass and subsequent bone loss are affected by genetics, nutrition, exercise, alcohol consumption, smoking, disease, and medication use. Hypogonadal men and men treated with glucocorticoids are at markedly increased risk for spine fracture, especially as they age and bone resorption is superimposed on age-related changes. Evaluation of osteoporosis in men should include, at minimum, measurements of gonadal function (if unknown), nutritional status, calcium homeostasis, and thyroid function. Hypogonadal men should respond to testosterone replacement therapy. Men with high-turnover osteoporosis should respond to osteoclast-inhibitor therapy, and men with decreased osteoblast function should respond to stimulators of bone formation. Long-term effects of the various treatments on the rate of hip fracture are unknown, and the degree to which osteoporosis in men can be reversed is unclear. PMID- 8506184 TI - Primary osteoporosis. Methods to combat bone loss that accompanies aging. AB - Osteoporosis is a major public health problem in the United States. The key to its management is prevention by ensuring adequate amounts of calcium, vitamin D, and protein and exercise throughout life. When a significant amount of bone mass has been lost, therapeutic interventions are aimed at preventing further loss with use of antiresorptive agents (ie, estrogen, progestin, calcitonin, and bisphosphonates). Use of pharmacologic agents that stimulate bone formation is still in experimental stages. Research efforts focusing on prevention, diagnosis, and treatment of osteoporosis are in progress and should provide improved strategies in the future. PMID- 8506186 TI - Photoaging. Cosmetic effects of sun damage. AB - Given the many ways our culture promotes deeply tanned skin as a symbol of beauty, health, and even happiness, physicians face an uphill battle in promoting the healthy aspects of a pale complexion. Not only can excessive solar exposure accelerate and intensify aging in skin, it can also lead to serious health risks. Drs Browder and Beers tell why photoaging happens and how to prevent it. PMID- 8506187 TI - Relationship between smoking, weight and attitudes to weight in adolescent schoolgirls. AB - A total of 1,932 schoolgirls aged 11-18 from seven schools in the South London area were surveyed using questionnaires which addressed eating patterns, body weight history, attitudes to body weight and shape, menstrual history and current smoking behaviour. They were also weighed and their height was measured. Twelve per cent of the girls were regular smokers and 10% smoked seven or more cigarettes over a 4 day period. Amongst girls aged 14 and over, 15% smoked regularly and a further 9% occasionally. A significant relationship was found between smoking and weight. Smokers were more likely to be moderately overweight in relation to their peers and to have been worried about their weight at some stage. There were differences between girls in state schools and those in independent schools with regard to smoking behaviour and weight. The findings have implications for anti-smoking strategies and health education generally. PMID- 8506188 TI - Overweight--a common problem among women treated for hyperthyroidism. AB - We sent out a questionnaire to 112 women treated for diffuse toxic goitre 2-5 years earlier to evaluate the prevalence of problems with overweight after the disease. Of 87 responders, about 50% (irrespective of surgical or radioiodine treatment) reported weight problems, and we randomly selected 40 of these women (20 with and 20 without reported weight problems) for a clinical follow-up (32 appearing). At the follow-up examination (mean 4 years after treatment for hyperthyroidism), 27 women had a higher weight than their estimated premorbid weight. The weight gain correlated with the estimated premorbid body mass index (BMI; P < 0.005), indicating that excess weight gainers may have had a premorbid problem now exaggerated in the post-hyperthyroid period. However, many women with a BMI within the limits stated to be ideal (21-25 kg/m2) also showed dramatic increases in weight. In contrast, the average middle-aged woman in our region did not appear to have gained in weight during a corresponding time period as judged from a longitudinal population study. Women with reported weight problems (mean weight increase 15.6%, n = 16) did not differ from women without (mean weight increase 6.7%, n = 16) as regards pretreatment hormone levels, method of treatment, (change of) smoking habits or post-treatment levothyroxine administration, or in serum concentrations of thyroid hormones, thyrotrophin, cortisol, procollagen-III-peptide, cholesterol, HDL cholesterol or triglycerides. Women with hyperthyroidism should be informed about the risk of gaining weight after therapy and given early support as to dietary and lifestyle change. PMID- 8506189 TI - Histopathological examination of specimens removed during directional coronary atherectomy in patients presenting with crescendo angina show mural thrombus. AB - Thrombus formation over a fissured coronary atheromatous plaque has been shown by post mortem histological examination to be the pathophysiological mechanism responsible for myocardial ischaemia in those patients who died following a crescendo pattern of angina. Histological examination of plaques responsible for a crescendo pattern of angina in patients who do not die has not been available until recently. We describe two patients who presented with a crescendo pattern of angina. A new technique of coronary revascularization, directional coronary atherectomy, produced symptomatic relief and resolution of myocardial ischaemia. Histological examination of material from the stenosis responsible for their myocardial ischaemia, obtained using this technique, confirmed thrombus formation overlying a fissured atheromatous plaque. PMID- 8506190 TI - Subcutaneous versus intravenous administration of heparin in the treatment of deep vein thrombosis; which do patients prefer? A randomized cross-over study. AB - Patient preference for intravenous or subcutaneous heparin in the treatment of deep venous thrombosis was assessed in a randomized cross-over study. Twenty patients with venographically proven deep venous thrombosis were randomized to receive subcutaneous or intravenous heparin for 3 days followed by 3 days of the other treatment. Discomfort at the injection site, assessed by visual analogue scale, was significantly less for the subcutaneous than the intravenous administration route (P < 0.001), mobility was thought to be better when receiving subcutaneous heparin (P < 0.005) and patients' overall preference was for subcutaneous treatment (P < 0.001). PMID- 8506191 TI - Comparison of nisoldipine and nifedipine as additional treatment in hypertension inadequately controlled by atenolol. AB - Twenty-eight patients (11 Caucasian, 17 black) whose blood pressure was more than 160/96 mmHg after 4 weeks on placebo added to atenolol 100 mg/day were randomly given, in addition, nisoldipine 10 mg or nifedipine 20 mg each twice a day for 8 weeks in a double-blind cross-over study. There was a statistically significant (P < 0.001) fall in blood pressure with no change in heart rate, both supine and erect, on both drugs. There were no significant differences between nisoldipine and nifedipine. Adverse effects were recorded in 15%, 17% and 35% of the patients available for safety comparison for placebo, nisoldipine and nifedipine, respectively. There were no significant differences between the black and Caucasian patients in blood pressure responses, although the study had only a low power to detect these. However, the fasting serum triglyceride levels at the end of both calcium antagonist treatment periods were highly significantly lower in the black patients compared with the Caucasian patients. Nisoldipine, which has a higher coronary vascular selectivity and less negative inotropism than nifedipine, is as effective and as well tolerated as nifedipine in patients whose hypertension is inadequately controlled on atenolol. It may have a special role in hypertensive patients with impaired left ventricular function. PMID- 8506192 TI - Gastric acid secretion in typhoid fever. AB - Gastric acid secretion was studied in 20 patients with typhoid fever (Group A), ten patients with fever other than typhoid (Group B), and ten healthy adults of matched age and sex (Group C). Patients with typhoid showed reduced acid secretion at the time of fever and one week after subsidence of fever as compared to Group C. In uncomplicated patients (Group A1), these values rose thereafter but in complicated patients (Group A2) they remained low even 12 weeks after subsidence of fever. This suggests that these patients had pre-existing hypochlorhydria which predisposed them to a severe form of disease. There may be many factors playing a significant role in making typhoid patients more prone to develop complications but the importance of gastric acid levels has also to be considered. PMID- 8506193 TI - Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy. AB - Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy. PMID- 8506194 TI - Occupational lung diseases other than asthma. PMID- 8506195 TI - Primary tumours of the duodenum. AB - Six primary duodenal tumours were diagnosed in our 300 bed institute during a period of 10 years. Two patients had benign tumours (leiomyoma and carcinoid) and four had malignant tumours (adenocarcinoma). The most common manifestation was severe iron deficiency anemia. Diagnosis was usually delayed (with a mean time of 7.7 months from initial complaints), endoscopy being the most common and useful diagnostic tool. A curative procedure was performed in two patients. Patients with unexplained chronic iron deficiency anaemia should undergo thorough gastrointestinal evaluation, including the small intestine, as a curable disease may be found to be the source of the complaint. PMID- 8506196 TI - A safe and simple technique for exchanging central venous catheters. AB - A safe and simple technique for exchanging central venous catheters is herein described. Our technique is based on a modification of Seldinger's method, in which a new outer sheath is introduced over the previous catheter as a guidewire in order to simplify the exchange of central venous catheters. This technique can be successfully performed by new residents and can be applied to the exchange of clotted catheters. PMID- 8506197 TI - Gait disturbances in the acute medically ill elderly. AB - The characteristics of acute deterioration in truncal movements, posture and gait were studied in patients admitted with acute non-neurological disease. Reversible gait abnormalities with characteristics of a 'lower-half parkinsonism' were associated with a disorder of axial movement, disability (as assessed by an activities of daily living score), and low mental test score. There was no association of gait dysfunction with tests of upper limb apraxia. An 'at risk' sub-group of elderly patients was identified who during an acute illness lose their walking independence, of whom some also have great difficulty performing axial movements. Furthermore, any assessment of locomotor and axial movement in elderly patients must consider that any impairment may be the result of an acute medical illness. PMID- 8506199 TI - Useless hand of Oppenheim--magnetic resonance imaging findings. AB - A patient with multiple sclerosis developed a useless, deafferented left hand, as described previously by Oppenheim. Magnetic resonance imaging demonstrates that this is caused by an ipsilateral plaque of demyelination in the posterior columns of the cervical cord. PMID- 8506198 TI - Optochiasmatic tuberculoma causing progressive visual failure: when has medical treatment failed? AB - A 5 year old girl with tuberculous meningitis developed progressive visual failure during in-patient anti-tuberculous chemotherapy due to an ophthochiasmatic tuberculoma. This was successfully managed by prolonged high dose corticosteroids and continued anti-tuberculous therapy resulting in complete visual and psychosocial recovery. PMID- 8506200 TI - Blind drunk: alcoholic pancreatitis and loss of vision. AB - Acute loss of vision and alcoholic intoxication suggests the possibility of methanol poisoning. In this report we describe an alcoholic patient who complained of blindness after recovering from alcoholic pancreatitis and delirium tremens. Visual acuity was severely impaired and fundoscopy revealed florid bilateral cotton wool spots and a cherry red spot at the right macula. Such appearances have previously been reported in cases of post-traumatic visual loss, and may share a common aetiology of fat embolization. The association between alcoholic pancreatitis and visual loss is rare, and fundal examination should be performed on all patients with pancreatitis, especially those who complain of visual disturbance. PMID- 8506201 TI - Solitary plasmacytoma of bone--a rare disorder with an unusual evolution. AB - A 40 year old woman presented with a spinal epidural tumour, which on histology was shown to be a plasmacytoma. At that time she had no evidence of multiple myeloma. Ten months later, she developed a second isolated plasmacytoma in the spleen, for which she underwent splenectomy. Two years after her initial presentation she had another recurrence in the liver, followed by a full-blown picture of multiple myeloma. The myeloma was progressive and resistant to all forms of chemotherapy. She finally died of a massive gastrointestinal haemorrhage. The clinical features, natural evolution and management of solitary plasmacytomas are discussed. PMID- 8506202 TI - Intimal sarcoma of the superior vena cava. AB - A case of superior vena cava syndrome caused by a primary intimal sarcoma of the superior vena cava is described. The known causes of superior vena caval obstruction are discussed, together with the difficulties in identifying the underlying lesion. The possibility of a primary superior vena caval neoplasm as a cause of superior vena caval obstruction should be considered in patients presenting with superior vena caval syndrome. PMID- 8506203 TI - Primary liposarcoma of the omentum. AB - This report is of a 54 year old female with omental liposarcoma. Diagnosis was made by ultrasonography, computed tomography, angiography and operation. The patient was treated by surgical excision. The histological examination revealed that the tumour was round cell liposarcoma. This is the first report to our knowledge of round cell liposarcoma of the omentum. PMID- 8506205 TI - Diagnosis and management of ventricular tachycardia. PMID- 8506204 TI - 17 alpha-Hydroxylase deficiency with persistence of mullerian ducts in a genotypic male and paradoxical aldosterone secretion. AB - We report a case of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in a Chinese genotypic male patient. Despite the male genotype, normal female external genitalia were present and with the introduction of cyclical oestrogen therapy withdrawal bleeding occurred, confirming the presence of functional endometrial tissue. We believe this to be the first report of persistent Mullerian duct structures in a genotypic male with 17 alpha hydroxylase deficiency. It could be explained by either impaired secretion or impaired action of anti-Mullerian hormone. Further, contrary to the usual finding of suppressed aldosterone secretion, this patient had measurable levels of plasma aldosterone. PMID- 8506206 TI - The chronic fatigue syndrome. PMID- 8506207 TI - Addisonian crisis presenting with a normal short tetracosactrin stimulation test. PMID- 8506208 TI - The renal effects of dopamine and dobutamine in stable chronic heart failure. PMID- 8506209 TI - Localized scleroderma and hemiatrophy in association with antibodies to double stranded DNA. PMID- 8506210 TI - Oncology. PMID- 8506211 TI - IgA nephropathy in hereditary angioedema. AB - Hereditary angioedema is an autosomal dominant disorder of the complement system in which there is a deficiency of the inhibitor of the activated first component of complement. We have previously reported on three generations of a family with classic hereditary angioedema. Three members of this family have now developed IgA nephropathy. The association of hereditary angioedema with various immunoregulatory disorders has been previously reported but this is the first report of IgA nephropathy in association with this condition. PMID- 8506212 TI - [Identity status in the transition from adolescence to young adulthood: an empirical comparative study of psychiatric patients and healthy control probands]. AB - The identity concept of Erikson has been operationalised by Marcia. Its basic dimensions are the exploration of possible alternatives in the various areas of psychosocial life and the commitment to personal solutions. Accordingly four status of identity are differentiated: identity achievement, foreclosure of identity, moratorium, identity diffusion. Patients and controls hold a similar position regarding identity achievement, but controls more decisively reject the remaining identity statuses thereby reaching an identity profile of higher maturity. Both groups show a strong endeaver not to solve the issues of identity by mere assimilation of extern role patterns via their parents. Among non psychotic patients compared to psychotic patients this very endeaver is more pronounced. Patients with affective disorders show a comparably mature profile of identity. Among schizophrenic patients those with a disorganized type seem to indicate that they are lest able to invest the logic of identity formation by exploration and commitment or cannot even understand it. The subjective measures in relation to identity status are opposed to a list of events indicating an "adolescent crisis" in the developing years from puberty to late adolescence for patient and control group. PMID- 8506213 TI - [Artefacts as a creative process--a case report]. AB - The psychological treatment on a 13-year-old girl with dermatitis artefacta during dermatological inward treatment is presented. On the base of the biographic background the psychodynamic conflict, underlying the manipulative behaviour, is revealed. With the help of pictorial expressions and a special hypnotherapeutic technique ("working with parts") the young patient succeeds in integrating her ambivalent feelings and in getting a deeper insight of her problems. The manipulations are regarded as a creative attempt to solve an intrapsychic conflict of ambivalence. PMID- 8506214 TI - [Team supervision in pediatric day care facilities. Experiences with special psychologic child rearing technique]. AB - This article reports about experiences made with team supervision in child care centers. Some thoughts about socio-political and relationship-psychological conditions for the work pedagogues are first described. These are followed by observations and findings from the supervision groups, referring to implicit occupational norms of the pedagogues and their partially unreflected helping impulses. The experiences made are encouraging regarding continuing and intensifying the supervision work. PMID- 8506215 TI - [Countertransference as therapeutic instrument in analytic child psychotherapy]. AB - In the process of psychoanalysis or psychoanalytical therapy countertransference plays a significant role: On the one hand still unconscious countertransference reactions of the therapist hinder the progress of the patient, especially when they lead to an acting-out of the countertransference resistance. On the other hand every analyzed countertransference reaction helps directly in understanding the patient and furthers of the process of therapy itself. This also applies to analytical child-therapy, which is demonstrated by means of some case histories. PMID- 8506216 TI - Preterm delivery rate and fetal outcome in structurally affected twin pregnancies: a retrospective matched control study. AB - Data from 23 twin pregnancies with one structurally affected fetus were compared with data from 23 twin pregnancies with proven absence of structural fetal anomalies and matched for maternal age, parity, and year of delivery. The preterm delivery rate (< 37 weeks) was high in both groups but not significantly different (57 vs. 48 per cent). Perinatal mortality was significantly higher in the structurally affected twin pregnancies (65 vs. 9 per cent). In the affected twins, birth weight of the anomalous fetus was significantly lower than that of the normal co-twin. Since there was no difference in the incidence of maternal disease (hypertensive disorders, diabetes), it was concluded that the higher perinatal mortality was determined mainly by the nature of the anomaly and not by the preterm delivery rate. PMID- 8506217 TI - Prenatal detection of monosomy 21 mosaicism. AB - We report a case of chromosomal mosaicism for monosomy 21 revealed in amniotic fluid cell culture. Ultrasound examination at 19 weeks' gestation showed in utero growth retardation and a complex cardiac malformation. A repeated amniocentesis confirmed the presence of monosomy 21 mosaicism. In view of the sonographically detected fetal abnormalities, termination of pregnancy was elected. PMID- 8506219 TI - Mosaicism in chorionic villus sampling: an analysis of incidence and chromosomes involved in 2612 consecutive cases. AB - The incidence of chromosome mosaicism was analysed in 2612 consecutive chorionic villus sampling (CVS) cases. True mosaicism was found in five cases (0.19 per cent). Confined placental mosaicism (CPM) occurred in 51 cases (1.9 per cent). The chromosomes most frequently encountered in CPM were 2, 7, 8, and the sex chromosomes. Three types of CPM as proposed by Kalousek et al. (1992) were observed. Cases with CPM had a statistically significant association with spontaneous abortion (chi 2 = 3.92, p < 0.05). Based on the data analysed, we conclude that (1) CPM is as likely to occur in cultured chorionic villi as in the direct preparation; (2) as with amniocyte culture, chromosome 2 mosaicism occurs commonly in villus culture; (3) the incidence of false-positive results can be greatly reduced and concern about maternal cell contamination can be alleviated by using both direct cytotrophoblast preparation and cultured chorionic stroma cells in all cases; and (4) follow-up cytogenetic and obstetrical studies, such as ultrasound and fetal monitoring, should always be considered in cases where CPM is suspected. PMID- 8506218 TI - Heteroduplex formation: a potential source of genotyping error from PCR products. AB - The formation of heteroduplexes from polymerase chain reaction (PCR) products has recently become a diagnostic tool that is routinely used for the prenatal detection of small deletions or insertions in a number of disease-causing alleles. We present evidence illustrating that heterozygous PCR products can manifest 'invisible' heteroduplexes that can ultimately lead to genotyping errors. Justifications for these 'invisible' heteroduplexes and requisite parameters to optimize their detection are presented. PMID- 8506220 TI - Complex mosaicism associated with trisomy 9. AB - Fetal karyotypes can be routinely obtained by chorionic villus biopsy, amniocentesis, or fetal blood sampling. Interpretation of results and subsequent counselling can be complicated by pseudomosaicism or mosaicism confined to the placenta or other tissues. We illustrate this by reporting a case of an abnormal fetus with a total of three karyotypically different cell lines (46,XX; 47,XX, +9; and 47,XX, +del(9) (q11) in different tissues (placenta, lung, gonad, and skin). PMID- 8506221 TI - Direct prenatal diagnosis of Friedreich's disease. PMID- 8506222 TI - Pregnancy associated plasma protein A as a marker for Down syndrome in the second trimester of pregnancy. PMID- 8506223 TI - Low maternal serum oestriol and chorionic gonadotropin in the prediction of adverse pregnancy outcome. PMID- 8506224 TI - A further case of prenatally detected mosaic isochromosome 20q. PMID- 8506225 TI - First trimester amniocentesis between the seventh and 13th weeks: evaluation of the earliest possible genetic diagnosis. PMID- 8506226 TI - Rapid detection of aneuploidy in uncultured chorionic villus cells using fluorescence in situ hybridization. AB - Rapid detection of aneuploidy using chromosome-specific repetitive DNA probes and the potential diagnostic accuracy of fluorescence in situ hybridization (FISH) on interphase cells of chorionic villus samples (CVS) are presented. Analyses demonstrated the ability to correctly identify aneuploidy using FISH in uncultured CVS. Our preliminary investigation suggests that this technique offers a significant clinical potential to circumvent problems of culture, time, and cost in cytogenetic analysis. PMID- 8506227 TI - 'Late' chorionic villus sampling: cytogenetic aspects. AB - Cytogenetic data about 145 chorionic villus samples obtained between the 13th and 35th week of gestation are reported. 'Late' chorionic villus sampling (CVS) was used to resolve different situations: failed amniotic fluid cell cultures (5 cases); confirmation of an abnormal karyotype, previously diagnosed as mosaic (14 cases); and ultrasound fetal malformation (23 cases). Most of the samples (103 cases) were analysed for the classical indications and in these cases, the principal aim was to obtain a rapid fetal karyotype. Excluding the cases used to check fetal karyotype, a chromosomal aberration was found in 11 out of 131 biopsies. In four cases of the group in which the fetal karyotype was checked (14 cases), the pathology observed at the first diagnosis was confirmed, while in the remaining ten cases the anomaly was not observed. PMID- 8506228 TI - Evaluation of amniotic fluid cell filtration: an experimental approach to early amniocentesis. AB - Prior to a prospective application of amniotic fluid (AF) cell filtration to early amniocentesis, we tested the technique on a surplus from mid-trimester samples. By using the same sample size of 5 ml in experiments with a filter and in routine diagnostic procedures (control), we evaluated an optimal filter system. The prolonged culture time of filtered cells and the reduced number of clones are most probably due to mechanical stress (filtration pressure), whereas loss of the cells by adhesion to the filter system, and an AF-free culture medium (growth factors) are suggested to be less important. The AF cells are very sensitive to mechanical stress. Slow filtration (< or = ml AF/min) through filters with a high porosity and the largest possible pore size should be preferred. A mixed cellulose ester filter membrane with a pore size of 5.0 microns proved to be the most efficient, allowing harvest of the filtered cells after only a slight prolongation of the culture time (+2.4 days) compared with unfiltered aliquots. A filter set with a bypass connected by three-way taps allows cell filtration during either aspiration or reinjection of the AF. Cell filtration after amniocentesis and consecutive reverse flushing of the membrane with the appropriate amount of culture medium proved to be the best with regard to easy handling and reducing the risk of bacterial contamination. PMID- 8506229 TI - A prospective cytogenetic study of third-trimester placentae in small-for-date but otherwise normal newborns. AB - Data in the literature suggest that confined placental mosaicism might be associated with intrauterine growth retardation. However, this association may be coincidental and due to bias of ascertainment. We therefore started a prospective study based on the cytogenetic evaluation of placentae derived from growth retarded newborns. We further minimized possible bias by excluding those small for-date infants displaying findings which already could explain intrauterine growth retardation (mothers who are smokers, multiple pregnancies, gestosis, dysmorphic infants). In a collection of 71 small-for-gestational age newborns, we did not see a single case of true confined placental mosaicism. PMID- 8506230 TI - Economic assessment of maternal serum screening for Down's syndrome using human chorionic gonadotropin. AB - The effectiveness and costs of prenatal screening programmes for Down's syndrome using maternal serum markers will vary significantly depending on the biological cut-off values chosen in order to select women, at each maternal age, who will be sent for amniocentesis. On the basis of the first French prospective study of human chorionic gonadotropin (hCG) measurement in maternal serum, this paper shows that the screening protocol currently used in France, where hCG cut-off values are defined in order to offer amniocentesis to women of all ages with a 1 per cent fetal risk of Down's syndrome, would detect 64.06 per cent of all cases of trisomy 21 at birth and would be highly profitable for the French social security system. On the basis of a representative sample of 100,000 pregnant women, the total costs of screening would reach $8,302,000 but would generate net potential savings of $32,186,000 in terms of life-long costs of care for trisomic 21 children which would be 'avoided' by termination of pregnancy following a positive diagnosis of Down's syndrome. Economic assessment shows that cost benefit analysis would justify lower hCG cut-off values and a higher detection rate of fetal Down's syndrome (74.45 per cent) than the current French protocol. This paper concludes that it is ethical and value-laden issues, such as the consequences for women and couples of false positives and false negatives of screening, rather than economic and financial arguments that may set limits to the utilization of screening for Down's syndrome using maternal serum markers like hCG. PMID- 8506231 TI - Evidence of a second gamete fusion after the first cleavage of the zygote in a 47,XX,+18/70,XXX,+18 mosaic. A remarkable diploid-triploid discrepancy after CVS. AB - A 70,XXX,+18 karyotype was found by chorionic villus sampling, while the fetal fibroblast culture of the affected fetus revealed a 47,XX,+18 karyotype. From several possible mechanisms, we assume that a second gamete fusion occurred after the first cell division of the zygote. According to this interpretation, the mosaicism arose in very early pregnancy (at the two-cell stage). This discrepancy can therefore be explained by selection pressure, due to the differentiation processes in the embryonic tissues. PMID- 8506232 TI - Trisomy 15 in chorionic villi and Prader-Willi syndrome at birth. PMID- 8506233 TI - Effect of processing on the mycoflora and aflatoxin B1 level of a cassava-based product. AB - Cassava bread was prepared by pre-gelling, battering and baking cassava flour to which were added, in moderate amounts, sugar, yeast solution and edible oil. Baking was at 215 degrees C for 40 min. No mould was isolated from the cassava bread and the mean value of aflatoxin B1 (AFB1) for the three subsamples of cassava bread was 0.03 microgram/kg. The cassava tuber (Manihot esculenta Crantz), which was used for the production of cassava bread had an initial AFB1 level of 1.91 micrograms/kg and the dominant mycoflora were Penicillium oxalicum, Aspergillus flavus, Fusarium spp and some unidentified fungi. PMID- 8506235 TI - The quality of tomato for canning as affected by combined chloride, nitrate and osmotic potential of the nutrient solution. AB - The quality of tomato fruit and juice (Lycopersicon esculentum L. cv. VF M82-1-8) grown in an aerohydroponic system in a greenhouse was affected by the level of Cl and NO3-, and by the osmotic potential (OP) of the nutrient solutions. The total suspended solids (degrees Brix) in the fresh juice increased from approximately 4.0 in the nonsaline solutions (OP approximately -0.05 MPa) to approximately 5.6 5.8 in the saline solutions (OP approximately -0.45 MPa). Juice acidity was similarly affected by the Cl-, NO3- and OP levels in the nutrient solutions. Less affected, the ascorbic acid content of juice, was lowest (approximately 8-9 mg/100 cc) in the high-NO(3-) -nonsaline solution treatments, and was between 10 and 12 mg/100 cc at OP levels greater than approximately -0.2 MPa. NO3- in the juice was high (approximately 60 mg/L) under low OP conditions (approximately 0.05 to -0.1 MPa), especially when combined with high NO3- levels, and lower (between 8 and 30 mg/L) in plants exposed to saline conditions (low OP). Fruit puffiness (boxiness) was reduced markedly by salinity and was not considerably affected by the NO3-/Cl- ratio, while fruit firmness was influenced by both factors. PMID- 8506234 TI - The physico-chemical properties of the seed and seed oil of Jatropha gossipifolia. AB - The physico-chemical properties of the seed and seed oil of Jatropha gossipifolia were assessed by standard methods. The seed contains 35.8% crude oil of iodine value 107.25, 13.40% protein, 9.25% fibre, 30.32% carbohydrate and 6.0 g/kg saponins. The fatty acid composition of the seed oil was determined by GC-MS. Caprylic, myristic, palmitoleic, palmitic, oleic, stearic, linoleic, vernolic, arachidic, behenic and lignoceric acids were found. PMID- 8506236 TI - Food potentials of some unconventional oilseeds grown in Nigeria--a brief review. AB - A brief review of literature on kernels of Citrullus and Cucumeropsis ('egusi' melon) species, Telfairia occidentalis (fluted pumpkin), Lagenaria (gourd) species of all of Cucurbitaceae family and other oilseeds such as Pentaclethra macrophylla (African oil bean), Parkia spp. (African locust bean) both of Mimosaceae family and Butyrospermum paradoxum (shea butter) of Sapotaceae family which are grown and widely used as food in Nigeria is presented. The kernels of species of Cucurbitaceae form the bulk of unconventional oilseeds used for food in Nigeria. The nutritional value of some of the kernels and the physicochemical properties and storage stability of the oils obtained from them are discussed. The various consumable forms in which they exist are also described. The problems and prospects of these neglected oilseeds in Nigeria are highlighted. PMID- 8506237 TI - Methionine-containing proteins in two Phaseolus vulgaris cultivars with different methionine bioavailabilities. AB - The full utilization of legumes as human food is limited by a deficiency of sulfur amino acids, low protein digestibility, low methionine bioavailability and the presence of anti-nutritional factors. A new cultivar of Phaseolus vulgaris (Carioca 80) has 56.8% available methionine, compared with 29.3% availability in the parent cultivar Carioca. The total methionine content, denaturing gel electrophoretic patterns of methionine-containing proteins, and the percentage of phaseolins (the major storage proteins in Phaseolus) relative to the total protein are similar in the two cultivars. Although the digestibility of the two cultivars is similar, the increased biological value of Carioca 80 may indicate that there are differences in overall bean composition that affect protein hydrolysis and utilization. We suggest the tentative explanation that this is due to differences in the distribution of methionine in the methionine-containing proteins of the two cultivars. PMID- 8506238 TI - Changes in some constituents of pea seed during commercial canning. AB - Changes in crude protein (CP), non protein nitrogen (NPN), total sulphur (TS) contents, carbon/nitrogen (C/N) and nitrogen/sulphur (N/S) ratios and albumin protein (AP) were studied in four sizes of peas at various stages of the commercial canning process. Of all the parameters considered, NPN, AP, and TS showed the most regular trend to decrease during the commercial canning process. In this paper the use of these three parameters is proposed to obtain a Heat Treatment Index (HTI) applicable to raw, blanched and canned peas, according to the equation: HTI = (NPN x AP)/TS. PMID- 8506239 TI - A simple, low energy requiring method of coagulating leaf proteins for food use. AB - A simple method for coagulating proteins in aqueous leaf extract, through microbial fermentation, has been reported. The Leaf Protein Concentrate (LPC) obtained through this fermentation has been compared with those obtained through conventional heat coagulation methods to show that the former improves the yield and nutritional quality of LPC. PMID- 8506240 TI - In vitro availability of iron from selected nuts and oilseeds. AB - Availability of iron from sixteen varieties of selected nuts and oilseeds was assessed by in vitro method. Wide and significant variations were recorded in the contents of total and ionisable iron and in the bioavailability of iron of the nuts and oilseeds. The total iron content was the highest in nigre seeds and the lowest in linseed seeds. Bioavailability of iron was significantly high from pistachio nut and almond and markedly low from groundnut. Most of the nuts and oilseeds were found to have less than 10 percent of bioavailability of iron, hence, they were not considered as good sources of iron among plant foods. PMID- 8506242 TI - Effect of amino acid supplementation on protein quality of soy-based infant formulas fed to rats. AB - The powder forms of soy-based infant formulas obtained from four manufacturers were fed to weanling rats for two weeks, as the sole source of protein in diets containing 8% protein, 20% fat, and adequate amounts of minerals and vitamins. The relative protein efficiency ratio (RPER) and the relative net protein ratio (RNPR) values (casein + methionine = 100) of diets containing unsupplemented formulas were 71-81 and 78-85, respectively. Supplementation of the formula diets with lysine (0.2%), methionine (0.2%), threonine (0.1%) or tryptophan (0.05%) increased the level of the supplemental amino acid in rat serum but generally failed to improve the RPER or RNPR values. Addition of all four essential amino acids to the formula diets, however, caused a marked improvement in their protein quality (RPER or RNPR values = 100). The data suggested that proteins in soy based formulas could be marginally co-limited in several indispensable amino acids. PMID- 8506241 TI - Studies on the chemical composition and physico-chemical properties of seeds of some wild plants. AB - The Seeds of the fruits of some wild plants were analysed to establish their proximate compositions and the physico-chemical characteristics of the oils. The iodine values of the oils were not greater than 88 but the saponification values were in the range 157-261 mg KOH. Proximate values of the protein, oil and carbohydrate contents of the seeds suggest that they may be adequate for the formulation of animal feeds, subject to a knowledge of the levels of possible toxic substances. The Storage property of the oil from Lophira lanceolata seed were studied over a period of four weeks under conditions of light (ambient), darkness (ambient) and refrigeration. The iodine value of the oil decreased in all cases but much more so on exposure to light. In contrast, the peroxide value of the oil showed very little change under conditions of darkness and refrigeration over the same period but increased by seven fold for the photo exposed oil. PMID- 8506243 TI - Improvement of the traditional method of ogiri production and identification of the micro-organisms associated with the fermentation process. AB - Fermented products were developed from different proportions of melon (Citrullus vulgaris schrad) and groundnut (Arachis hypogea) seeds after a 96 hour fermentation period. Proximate analysis, carried out on both fermented and unfermented samples, indicated that only the total carbohydrate content was appreciably reduced by the fermentation process. Micro-organisms responsible for fermentation were identified by gram staining and lactophenol staining, as bacteria and fungi. Identified bacteria were of the Bacillus and Acinetobacter species while the fungi were yeasts, rhizopus and mucor. Samples containing 50 100% melon showed a decrease in pH with increasing fermentation period. Bacteria were largely responsible in samples containing up to 75% groundnuts. Sensory analysis of dried fermented products after fortification with salt, ascorbic acid and flour indicated that they were acceptable. PMID- 8506244 TI - Alcohol production in submerged cashew pomace. AB - The variations in the total titratable acidity, hydrogen ion concentration, reducing sugar, soluble solids and alcohol contents of the supernatant of the submerged cashew pomace in a non-aseptic condition were investigated. The crude fibre content of the pomace was also determined during fermentation. At intervals, the changes in microbial load in both the pomace and its supernatant were examined during the 14-day study. Fifty four percent of the total soluble solids (TSS) was utilised within 7 days of degradation while an increase of about 91% in the total titratable acidity occurred in the cashew pomace within the same period bringing its pH to 3.24. Acid hydrolysis of the pomace accounted for the relative high value of 2.15% TSS on the 8th day. Isolates of the genera Leuconostoc, Lactobacillus, Pediococcus, Aspergillus, Rhizopus and some yeast strains were obtained from the fresh pomace. The fungal colonies constituted about 76% of the population in the cashew pomace. The 86% drop in microbial population of the 8th day biodegraded pomace could be attributed to a decrease in nutrients of the substrate and the inhibitory effect of the organic acids produced during fermentation. PMID- 8506245 TI - Characterization of Chilean hazel nut sweet cookies. AB - A series of studies were carried out to test the effect of the incorporation of Chilean hazel nut flour in sweet cookies at the levels of 0%, 5%, 10%, 15% and 20%. The proximate chemical analysis of the different flour mixtures showed a regular increase from 7.2 to 12.2%, 14.5% to 18.8% and 1% to 2.2%, respectively, decreasing at the same time with the percentages of water and carbohydrates. Chemical amino acid scores of leucine and threonine in wheat flour improved with the incorporation of Chilean hazel nut flour. The farinographic evaluation made to the different blends showed several changes occurred with the incorporation of Chilean hazel nut flour to wheat flour. These included increase in water absorption, decrease in dough developing time and weakening of the dough. Sensory characteristics such as appearance, texture, flavor and also acceptability improved with the incorporation of Chilean hazel nut flour into the cookie formulas. PMID- 8506246 TI - Current topic: restriction of placental and fetal growth in the guinea-pig. PMID- 8506247 TI - Identification of trophoblastic giant cells as the initial principal target of early gestational murine enterovirus infection. AB - Theiler's murine encephalomyelitis virus (TMEV), a murine enterovirus, infects the majority of murine placentae and fetuses following inoculation in early gestation and infects most placentae but almost no fetuses in late gestation. The sequence of infection of TMEV following early gestation inoculation was studied. Mice were inoculated with TMEV on day 6 or 7 of pregnancy and sacrificed at intervals between 1 h and 4 days later. Culture of placenta-embryo units identified infection at 2, 3, and 4 days post-inoculation. In situ hybridization revealed TMEV RNA primarily in giant cells around the yolk cavity and in giant cells situated between the decidua and spongiotrophoblast layers of the placenta. Occasional decidual cells located near giant cells were also hybridization positive. The giant cells were immunohistochemically identified as fetally derived trophoblast cells. Giant cells are the earliest predominant target of TMEV infection following early gestation inoculation and appear to be an integral part of the pathogenesis of gestational murine enterovirus infection. PMID- 8506248 TI - Serotonin uptake in the ectoplacental cone and placenta of the mouse. AB - The neurotransmitter serotonin (5-HT) was localized in the ectoplacental cone (EPC) and placenta of the day 9-12 (E9-12) mouse embryo in vivo and in whole embryo cultures, using immunocytochemistry with a specific 5-HT antiserum. In uncultured conceptuses, 5-HT immunoreactivity (5-HT IR) was most intense in the EPC at E9 (2-7 somites), particularly in giant cells around the periphery. Nuclear staining was observed in lightly staining giant cells and in small cells in the core of the cone. By E10 (18-24 somites) 5-HT IR in the placenta was less intense and almost exclusively limited to giant cells, where it was localized to chromatin-like material in nuclei. The same pattern and level of 5-HT IR persisted through E12. In the placenta, 5-HT IR appeared to be most intense in giant cells located near aggregations of platelets in decidual blood vessels. 5 HT IR was enhanced in cultured conceptuses, and further increased when exogenous 5-HT was added to the culture medium. Immunoreactivity was greatly reduced by adding the 5-HT uptake inhibitor fluoxetine to the culture medium, or culturing conceptuses in medium containing 5-HT depleted rat serum. Thus, 5-HT was apparently taken up from the culture medium. In conceptuses exposed to exogenous 5-HT, immunoreactivity in the placenta appeared as a gradient from the giant cells to the inner layers, suggesting that these cells may transport 5-HT toward the embryo. No evidence of 5-HT synthesis by the EPC/placenta was found. These results suggest that 5-HT present in the EPC/placenta is due to uptake, not synthesis. Possible sources and functions of 5-HT in the developing placenta are discussed. PMID- 8506249 TI - Prostaglandin endoperoxide synthase kinetics in human amnion before and after labor at term and following preterm labor. AB - To determine whether the kinetics of prostaglandin endoperoxide synthase (PGHS, commonly known as cyclooxygenase) in human amnion change with labor onset or between preterm and term labor, a specific enzyme assay was developed and characterized. The assay was linear for time (0-8 min) and protein concentration (5-30 micrograms/250 microliters incubation volume). The optimum pH was 8.0-8.5, and the enzyme reaction reached saturation at 10-20 microM arachidonic acid. Flufenamic acid was more efficacious than ibuprofen in the presence of 1 mM tryptophan in inhibiting enzyme activity. The Km and Vmax of PGHS were determined in 10 amnions obtained at elective caesarean section before labor onset (CS) at 39.3 +/- 0.8 wk gestational age (mean +/- SD, range = 38.5-41 wk) and 9 amnions obtained following spontaneous labor and vaginal delivery (SL) at 39.6 +/- 0.8 wk (range = 38.5-41 wk). The Km values were 1.4 +/- 1.2 mumol/l (CS) and 2.2 +/- 1.5 mumol/l (SL) (not different). However, the Vmax increased significantly (p < 0.05) from 11 +/- 8 (CS) to 19 +/- 4 (SL) pg PGE2/micrograms protein/min. In eight preterm amnions obtained following spontaneous labor and delivery at 32.9 +/- 2.1 wk (range = 29-36 wk), the Km and Vmax were 2.0 +/- 1.2 mumol/l and 17 +/ 9 pg PGE2/micrograms protein/min, respectively. Neither of these values was different from those of CS or SL amnions. None of the preterm pregnancies displayed histological evidence of infection. These results suggest that an increase in the mean amnion PGHS maximum velocity occurs in association with the onset of labor at term. The mean Vmax of PGHS in amnions obtained from idiopathic preterm spontaneous deliveries is between the CS and SL term values, reflecting, perhaps, multiple etiologies for preterm delivery. PMID- 8506251 TI - Ultrastructural and immunohistochemical studies of Wharton's jelly umbilical cord cells. AB - In order to determine the significance of Wharton's jelly, the characteristics of these cells were examined by means of electron microscopy and immunohistochemistry. These cells possessed ultrastructural characteristics of both fibroblasts and smooth muscle cells, indicating that they are modified, rather than typical fibroblasts. Immunohistochemically those 'myofibroblasts' stained positive for actin, non-muscle myosin, vimentin and desmin. Staining for muscle myosin was negative, supporting the ultrastructural findings. As our results indicate that these cells can function in both fibrogenesis and cell contraction, we speculate that they may contribute to the elasticity of Wharton's jelly, by synthesizing collagen fibers, and participate in the regulation of umbilical blood flow by virtue of their contractile properties. PMID- 8506250 TI - Colchicine inhibits human trophoblast differentiation in vitro. AB - When cultured in keratinocyte growth medium, mononuclear cytotrophoblast cells aggregate into multicellular colonies which then fuse to form multinucleated syncytiotrophoblast. In an attempt to characterize better the mechanism of human trophoblast differentiation and to obtain information about the role of the cytoskeleton, experiments were performed using cytoskeletal-disrupting drugs and primary cultures of cytotrophoblast cells from term placentae. Addition of colchicine 6 h after plating permitted aggregation but the cells did not form syncytiotrophoblast, as revealed by staining for desmosomes and nuclei. Staining with an anti-tubulin antibody showed that microtubules were present in untreated control cells but absent in colchicine-treated cultures. If colchicine was added 24 h after plating, the cells also failed to differentiate. When cells were exposed to colchicine for the first 24 h after plating and then cultured in the absence of the drug, differentiation proceeded normally. Cells exposed to colchicine for 48 h and then incubated in the absence of the drug failed to form syncytiotrophoblast. The results suggest that a decision to differentiate is made between 24 and 48 h after plating. The effects of colchicine were observed between 2.5 and 250 microM. Beta-lumicolchicine blocked differentiation at 250 microM but was ineffective at lower concentrations. Colchicine also inhibited HCG secretion in a dose-dependent manner; beta-lumicolchicine only caused inhibition at 250 microM. Staining with antitubulin antibody revealed that lumicolchicine treated cells had intact microtubules. These results suggest a role for microtubules in trophoblast differentiation. PMID- 8506252 TI - [Bronchoalveolar lavage: an approach to the immunopathogenesis of interstitial lung diseases of unknown etiology]. PMID- 8506253 TI - [Pharmacologic characterization of formoterol in comparison with isoprenaline, fenoterol and salbutamol in tracheal muscle strips and lung membranes of the guinea pig]. AB - In severe asthma attacks, beta 2-sympathomimetics can lose part of their therapeutic potency possibly due to a predominance of contractile mediators. To elucidate this loss of potency, we chose tracheal smooth muscle strips as experimental model which were partially and maximally precontracted with 100 and 6,000 nmol/l carbachol, respectively, reflecting different contractile states of the smooth muscle strips. Both contractures were dose-dependently relaxed by fenoterol and salbutamol which are well established as beta 2-sympathomimetics, by a new compound (formoterol) and by isoprenaline as standard. In tracheal strips, partially precontracted with 100 nmol/l carbachol, all agonists induced maximum relaxation beyond basal tone thereby characterized as full agonists. In maximally precontracted tracheal strips beta-adrenergic relaxation was markedly attenuated for all agonists by 70-80%. Maximum relaxation by the beta 2 sympathomimetics was even smaller than that of isoprenaline. By these experiments, the beta 2-sympathomimetics were characterized as partial agonists. The intrinsic 'activities (IA) for relaxation were different for the 3 beta 2 sympathomimetics investigated. Intrinsic activities were 0.8, 0.6 and 0.6 for formoterol, fenoterol and salbutamol, respectively. In both group of experiments formoterol exhibited the lowest EC50 for relaxation, which was 20 and 50 times lower than that of fenoterol and salbutamol, respectively. To investigate, if the higher relaxant potency of formoterol correlated to a higher binding affinity for beta 2-adrenoceptors, we performed radioligand binding experiments in guinea pig lung membranes. The non-linear regression analysis of data revealed a high affinity of formoterol, which was 16- and 40-fold higher than that of fenoterol and salbutamol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506254 TI - [Mucoviscidosis--not a topic for pneumonologists?]. AB - Although cystic fibrosis (CF) is the most common lethal hereditary disease, adult physicians remain to be relatively unfamiliar with this disease. In Germany, more than 25 per cent of the 4,000 CF patients are adults, but are treated by paediatricians. The present paper aims to focus the pulmonologist's attention to this problem. A brief review is given on aspects of genetics, pathophysiology, diagnosis, and treatment. Centralized treatment by an experienced CF clinic is important not only for children, but also for adults, and the contribution of adult pulmonologists to the care of these patients is urgently needed. PMID- 8506255 TI - [Prevalence of tuberculosis in Stuttgart--results of routine tuberculin tests]. AB - From 1986 to 1991 a total of 12,835 tuberculin tests were carried through by the Public Health Office in Stuttgart. In this period the rate of positive reactions increased remarkably, with higher rates as usual, higher for Germans than for foreigners. Possible consequences are discussed. PMID- 8506256 TI - [A case of bronchial leiomyoma]. AB - Pulmonary leiomyomas are the least common benign tumors of the lung. These tumors originate from smooth muscles of the bronchial walls, peripheral small airways, or from perivascular smooth muscles. It is reported that the diagnosis of the tumor has been established bronchoscopically and proved with thoracotomy. The characteristics of the tumor and treatment modalities are discussed. PMID- 8506257 TI - [International consensus report on the diagnosis and treatment of bronchial asthma]. PMID- 8506258 TI - The Greek key motif: extraction, classification and analysis. AB - The Greek key is a very common structural motif in proteins. It has been traditionally defined as four beta-strands with '+3,-1,-1' topology. This definition encompasses motifs with several different three-dimensional structures. We have classified Greek keys, based on their hydrogen bonding patterns, into three groups with similar three-dimensional structures. All examples of Greek keys in each of these classes have been automatically extracted using a set of programs. Analysis of these examples shows the variability of secondary structure segment length and sequences of Greek keys even within one class. This variability suggests that no single folding pathway is likely to fit all Greek key structures. PMID- 8506259 TI - Atomic environments of arginine side chains in proteins. AB - A statistical analysis of the atomic environments of arginine side chains from 62 high resolution protein structures has been made. Using the definition of F.M. Richards (J. Mol. Biol., 82, 1-14, 1974), the protein data set was subdivided into 19 different atom types and their propensities to form atom contacts with the side chain atoms of arginine residues were calculated. For those arginine side chain-atom pairs classed as interacting, a detailed analysis of their geometries was carried out. This has included the contact separation (R) and the spatial distribution in terms of the spherical polar angles theta and phi. The geometrical distributions of the 19 different atom types were compared and contrasted to identify factors that are important for packing. From the results we find that polarity, covalent constraints, volume occlusion and solvent accessibility are the key determinants governing packing around arginine side chains. PMID- 8506260 TI - Secondary structure prediction for modelling by homology. AB - An improved method of secondary structure prediction has been developed to aid the modelling of proteins by homology. Selected data from four published algorithms are scaled and combined as a weighted mean to produce consensus algorithms. Each consensus algorithm is used to predict the secondary structure of a protein homologous to the target protein and of known structure. By comparison of the predictions to the known structure, accuracy values are calculated and a consensus algorithm chosen as the optimum combination of the composite data for prediction of the homologous protein. This customized algorithm is then used to predict the secondary structure of the unknown protein. In this manner the secondary structure prediction is initially tuned to the required protein family before prediction of the target protein. The method improves statistical secondary structure prediction and can be incorporated into more comprehensive systems such as those involving consensus prediction from multiple sequence alignments. Thirty one proteins from five families were used to compare the new method to that of Garnier, Osguthorpe and Robson (GOR) and sequence alignment. The improvement over GOR is naturally dependent on the similarity of the homologous protein, varying from a mean of 3% to 7% with increasing alignment significance score. PMID- 8506261 TI - A new substitution matrix for protein sequence searches based on contact frequencies in protein structures. AB - The instabilities of the native structures of mutant proteins with an amino acid exchange are estimated by using the contact energy and the number of contacts for each type of amino acid pair, which were estimated from 18,192 residue-residue contacts observed in 42 crystals of globular proteins. They were then used to evaluate a transition probability matrix of codon substitutions and a log relatedness odds matrix, which is used as a scoring matrix to measure the similarity between protein sequences. To consider amino acid substitutions in homologous proteins, base mutation rates and the effects of the genetic code are also taken into account. The average fitness of an amino acid exchange is approximated to be proportional to the structural stability of the mutant protein, which is then approximated by the average energy change of the protein native structure expected for the amino acid exchange with neglect of the energy change of the denatured state. In global and local homology searches, this scoring matrix tends to yield significantly higher alignment scores than either the unitary matrix or the genetic code matrix, and also may yield higher alignment scores for distantly related protein pairs than MDM78. One of advantages of this scoring matrix is that the equilibrium frequencies of codons and also base mutation rates can be adjusted. PMID- 8506262 TI - A computer vision based technique for 3-D sequence-independent structural comparison of proteins. AB - A detailed description of an efficient approach to comparison of protein structures is presented. Given the 3-D coordinate data of the structures to be compared, the system automatically identifies every region of structural similarity between the structures without prior knowledge of an initial alignment. The method uses the geometric hashing technique which was originally developed for model-based object recognition problems in the area of computer vision. It exploits a rotationally and translationally invariant representation of rigid objects, resulting in a highly efficient, fully automated tool. The method is independent of the amino acid sequence and, thus, insensitive to insertions, deletions and displacements of equivalent substructures between the molecules being compared. The method described here is general, identifies 'real' 3-D substructures and is not constrained by the order imposed by the primary chain of the amino acids. Typical structure comparison problems are examined and the results of the new method are compared with the published results from previous methods. These results, obtained without using the sequence order of the chains, confirm published structural analogies that use sequence-dependent techniques. Our results also extend previous analogies by detecting geometrically equivalent out-of-sequential-order structural elements which cannot be obtained by current techniques. PMID- 8506263 TI - Can the stability of protein mutants be predicted by free energy calculations? AB - The use of free energy simulation techniques in the study of protein stability is critically evaluated. Results from two simulations of the thermostability mutation Asn218 to Ser218 in Subtilisin are presented. It is shown that components of the free energy change can be highly sensitive to the computational details of the simulation leading to the conclusion that free energy calculations cannot currently be used to reliably predict protein stability. The different factors that undermine the reliability are discussed. PMID- 8506264 TI - Effects of deletion in the flexible loop of the protease inhibitor SSI (Streptomyces subtilisin inhibitor) on interactions with proteases. AB - The Streptomyces subtilisin inhibitor (SSI) is a proteinaceous protease inhibitor which inhibits serine proteases by forming a stable Michaelis complex. The flexible loop region (Thr64-Val69) is a very flexible region in an SSI molecule and its importance in interactions with proteases has been suggested, since conformational change of this loop was found to occur for the smooth binding of SSI with various proteases. In this study, mutated SSIs lacking one or two residues in this region were generated and the effects of deletions on the interaction with proteases were investigated. Deletion was introduced into mutated SSI(Lys73) and SSI(Gly70Lys73) both known to be trypsin inhibitors, to examine the effects of deletion on interactions with subtilisin BPN' or trypsin. The deletion of one residue (Gly66) caused increased inhibitory activity toward trypsin, indicating the protruding flexible loop hinders binding with trypsin. Reduction of such hindrance by one-residue shortening in this loop is shown to be effective for the interaction of SSI(Lys73) with trypsin. In contrast, one residue shortening had virtually no effect on inhibition toward subtilisin BPN'. Differences in the subsite structures of these proteases may have been the reason for this contrast. The deletion of two residues (Thr64 and Gly66) in this region converted SSI into a temporary inhibitor. Structural analysis of the degradation intermediate showed that the peptide bond at the reactive site of doubly deleted SSI was cleaved by subtilisin BPN' after its binding with protease. Thus, the irreversibility of the cleaved peptide bond at the reactive site of mutated SSI in the complex with protease may possibly be the cause for its temporary inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506265 TI - Site-directed and deletion mutational analysis of the receptor binding domain of the interleukin-6 receptor targeted fusion toxin DAB389-IL-6. AB - We have used site-directed and in-frame deletion mutational analysis in order to explore the structural features of the IL-6 portion of the diphtheria toxin related interleukin-6 (IL-6) fusion toxin DAB389-IL-6 that are essential for receptor-binding and subsequent inhibition of protein synthesis in target cells. Deletion of the first 14 amino acids of the IL-6 component of the fusion toxin did not alter either receptor binding affinity or cytotoxic potency. In contrast, both receptor binding and cytotoxic activity were abolished when the C-terminal 30 amino acids of the fusion toxin were deleted. In addition, we explored the relative role of the disulfide bridges within the IL-6 portion of DAB389-IL-6 in the stabilization of structure required for receptor-binding. The analysis of mutants in which the substitution of either Cys440, Cys446, Cys469 or Cys479 to Ser respectively, demonstrates that only the disulfide bridge between Cys469 and Cys479 is required to maintain a functional receptor binding domain. In addition, the internal in-frame deletion of residues 435-451, which includes Cys440 and Cys446, was found to reduce, but not abolish receptor binding affinity. These results further demonstrate that the disulfide bridge between Cys440 and Cys446 is not essential for receptor-binding. However, the reduced cytotoxic potency of DAB389-IL6(delta 435-451) suggests that the conformation and/or receptor binding sites associated with this region of the fusion toxin is/are important for maintaining the wild type receptor binding affinity and cytotoxic potency. PMID- 8506266 TI - Structure and functional complementation of engineered fragments from yeast phosphoglycerate kinase. AB - Previous studies have shown that, although the isolated structural domains of yeast phosphoglycerate kinase recover a quasi-native structure in vitro as well as in vivo, they do not reassociate nor generate a functional enzyme. The aim of this work was first to study the folding of complementary fragments different from structural domains and second to determine the requirements for their reassociation and functional complementation. The method used for producing rigorously defined fragments consists of the introduction of a unique cysteinyl residue in the protein followed by a specific cleavage by 5'5'-dithiobis(2 nitrobenzoate)/potassium cyanide at this residue. Two pairs of complementary fragments were thus obtained, 1-96/97-415 and 1-248/249-415. The structure and stabilities of the different fragments were studied. The short fragments, i.e. 1 96 and 249-415 were found to contain some secondary structure, but to have a low stability. Each large fragment has a high structural content and a stability close to that of the corresponding domain. In contrast to that observed with the isolated domains, a weak but significant complementation was observed for the two pairs of fragments; the pair of fragments 1-248/249-415 recovered 8% of the activity of the native enzyme upon complementation. An independent refolding of the complementary fragments before reassociation decreased the yield of complementation for the pair of fragments 1-96/97-415, but did not affect the complementation for the other pair (1-248/249-415). From the present data and previous work on the isolated domains, it appears that the correct folding of the isolated fragments is not a prerequisite for their complementation. PMID- 8506267 TI - Recursive ensemble mutagenesis. AB - We have developed a generally applicable experimental procedure to find functional proteins that are many mutational steps from wild type. Optimization algorithms, which are typically used to search for solutions to certain combinatorial problems, have been adapted to the problem of searching the 'sequence space' of proteins. Many of the steps normally performed by a digital computer are embodied in this new molecular genetics technique, termed recursive ensemble mutagenesis (REM). REM uses information gained from previous iterations of combinatorial cassette mutagenesis (CCM) to search sequence space more efficiently. We have used REM to simultaneously mutate six amino acid residues in a model protein. As compared to conventional CCM, one iteration of REM yielded a 30-fold increase in the frequency of 'positive' mutants. Since a multiplicative factor of similar magnitude is expected for the mutagenesis of additional sets of six residues, performing REM on 18 sites is expected to yield an exponential (30,000-fold) increase in the throughput of positive mutants as compared to random [NN(G,C)]18 mutagenesis. PMID- 8506268 TI - Tumor immunogenicity: how far can it be pushed? PMID- 8506269 TI - Assessing the genetic structure of microbial populations. PMID- 8506270 TI - Photoreactivation in humans. PMID- 8506271 TI - The human genome project. AB - The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities in the present phase of the project. Advances in mapping techniques have allowed good progress toward the specific goals of the project and are also providing strong corollary benefits throughout biomedical research. Actual DNA sequencing of the genomes of the human and model organisms is still at an early stage. There has been little progress in the intrinsic efficiency of DNA-sequence determination. However, refinements in experimental protocols, instrumentation, and project management have made it practical to acquire sequence data on an enlarged scale. It is also increasingly apparent that DNA-sequence data provide a potent means of relating knowledge gained from the study of model organisms to human biology. There is as yet little indication that the infusion of technology from outside biology into the Human Genome Project has been effectively stimulated. Opportunities in this area remain large, posing substantial technical and policy challenges. PMID- 8506272 TI - Hemopoietic stem-cell compartment of the SCID mouse: double-exponential survival curve after gamma irradiation. AB - It has been reported that SCID (severe combined immunodeficiency, scid/scid) mice are more radiosensitive than normal mice. In the present studies, graded doses of radiation were given to bone marrow cells from SCID mice, and double-exponential survival curves were observed for day-9 and day-12 colony-forming units in the spleen (CFU-S). Single-exponential curves were found for SCID CFU in in vitro assays for granulocyte/macrophage-CFUs and erythroid burst-forming units, as reported elsewhere. Since the size of this more resistant fraction seems to decrease with stem-cell maturation, the finding implies that this fraction is a primitive subpopulation of the stem-cell compartment. The mean lethal dose (D0), however, of this less sensitive SCID CFU-S is much less than the D0 of regular CFU-S in normal littermates. Spleen colonies produced by SCID bone marrow were relatively small and abortive. The size of these colonies decreased nearly exponentially with increasing doses of radiation. These colonies were believed to be produced by this less sensitive fraction of the stem cells, which carried residual injuries. The colonies produced by the sensitive fraction have disappeared, being killed by a relatively low dose of radiation. This observation might account for the high lymphomagenesis arising from primitive hemopoietic stem cells in SCID mice, because the smallness of the colonies suggests that there is unrepaired or misrepaired damage. Furthermore, this less sensitive fraction might be a source of the "leaky" change of T and B cells, possibly due to the induction of an equivocal repair system which appears in the later stages of life in the SCID mice. PMID- 8506273 TI - Alteration of Caenorhabditis elegans gene expression by targeted transformation. AB - We have produced strains carrying a synthetic fusion of parts of two vitellogenin genes, vit-2 and vit-6, integrated into the Caenorhabditis elegans genome. In most of the 63 transformant strains, the plasmid sequences are integrated at random locations in the genome. However, in two strains the transgene integrated by homologous recombination into the endogenous vit-2 gene. In both cases the reciprocal exchange between the chromosome and the injected circular plasmid containing a promoter deletion led to switching of the plasmid-borne promoter and the endogenous promoter, with a reduction in vit-2 expression. Thus in nematodes, transforming DNA can integrate by homologous recombination to result in partial inactivation of the chromosomal locus. The simplicity of the event and its reasonably high frequency suggest that gene targeting by homologous recombination should be considered as a method for directed inactivation of C. elegans genes. PMID- 8506274 TI - An integrated approach for identifying and mapping human genes. AB - We have developed a method for generating expressed-sequence maps of human chromosomes. The method involves several steps that begin with libraries of highly representative short cDNAs prepared by using random oligomers as primers. The cDNA inserts are amplified by PCR with flanking vector primers. Chromosomal region-specific cDNA packets are prepared by hybridization of the cDNA inserts to DNA derived from yeast artificial chromosomes (YACs) assigned to defined regions of human chromosomes. The cDNA packets are cloned into yeast chromosome fragmentation vectors and used for transformation of yeast bearing the YAC used for affinity purification. Sequences in the cDNAs undergo homologous recombination with the corresponding exons in the genomic DNA yielding a set of truncated YACs. Each unique truncation specifies the location of an exon in the YAC. Since all of the truncation events end with the same vector sequence, it is possible to rescue and sequence these ends to generate expressed sequence tags. The method couples rapid purification of region-specific cDNAs with precise mapping of their genes on YACs. Appropriately truncated YACs also provide easy access to gene regulatory sequences. We describe the feasibility of individual steps of the method using the factor IX (F9) gene as a model system and we present the mapping of several expressed sequences corresponding to a 330-kb YAC containing DNA from human chromosome 6p21. In addition, we obtained the sequence, including an intron-exon junction, flanking a particular truncation event. PMID- 8506275 TI - Reduced expression of a human V beta 6.1 T-cell receptor allele. AB - We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis. Limited sequence data demonstrated nucleotide differences that resulted in two amino acid changes between the two alleles in positions predicted to be important in major histocompatibility complex/antigen recognition. The present study demonstrates substantially reduced expression of mRNA from the disease-associated allele (V beta 6.1B) in peripheral blood and thymic tissue. The complete genomic sequence of both alleles revealed two additional amino acid changes in the V beta 6.1B gene as well as nucleotide differences in the promoter and intron. A cysteine-to-arginine substitution at position 92 in the disease-associated allele makes this a non-functional beta chain, since this conserved cysteine is involved with disulfide bonding to cysteine-23 to form an immunoglobulin-like domain structure, thus resulting in a potential hole in the T-cell receptor repertoire. PMID- 8506276 TI - Transmembrane signaling by an insulin receptor lacking a cytoplasmic beta-subunit domain. AB - To assess the function of the cytoplasmic domain of the insulin receptor (IR) beta subunit, we have studied a mutant IR truncated by 365 aa (HIR delta 978), thereby deleting > 90% of the cytoplasmic domain. HIR delta 978 receptors were processed normally to homodimers that were expressed at the cell surface where they bind insulin with normal affinity. Although these truncated IRs were inactive with respect to ligand-induced internalization and autophosphorylation, insulin stimulated endogenous substrate (pp185) phosphorylation significantly more in HIR delta 978 cells than in untransfected Rat1 cells. Importantly, despite absence of the beta-subunit cytoplasmic domain, fibroblasts expressing HIR delta 978 receptors displayed enhanced sensitivity to insulin for stimulation of glucose incorporation into glycogen, alpha-aminoisobutyric acid uptake, thymidine incorporation, and S6 kinase activity compared with parental fibroblasts. Insulin also induced the expression of the protooncogene c-fos and the early growth response gene Egr-1 in HIR delta 978 cells far greater than in parental Rat1 fibroblasts. Furthermore, an agonistic monoclonal antibody specific for the human IR stimulated insulin action in fibroblasts expressing wild-type human IR but had no effect on HIR delta 978 cells. In conclusion, the HIR delta 978 truncated IRs appear to confer enhanced insulin sensitivity by augmenting the signaling properties of the endogenous rodent IRs. PMID- 8506277 TI - How clonal are bacteria? AB - Data from multilocus enzyme electrophoresis of bacterial populations were analyzed using a statistical test designed to detect associations between genes at different loci. Some species (e.g., Salmonella) were found to be clonal at all levels of analysis. At the other extreme, Neisseria gonorrhoeae is panmictic, with random association between loci. Two intermediate types of population structure were also found. Neisseria meningitidis displays what we have called an "epidemic" structure. There is significant association between loci, but this arises only because of the recent, explosive, increase in particular electrophoretic types; when this effect is eliminated the population is found to be effectively panmictic. In contrast, linkage disequilibrium in a population of Rhizobium meliloti exists because the sample consisted of two genetically isolated divisions, often fixed for different alleles: within each division association between loci was almost random. The method of analysis is appropriate whenever there is doubt about the extent of genetic recombination between members of a population. To illustrate this we analyzed data on protozoan parasites and again found panmictic, epidemic, and clonal population structures. PMID- 8506278 TI - Evidence for lack of DNA photoreactivating enzyme in humans. AB - Photoreactivating enzyme (DNA photolyase; deoxyribocyclobutadipyrimidine pyrimidine-lyase, EC 4.1.99.3) repairs UV damage to DNA by utilizing the energy of near-UV/visible light to split pyrimidine dimers into monomers. The enzyme is widespread in nature but is absent in certain species in a seemingly unpredictable manner. Its presence in humans has been a source of considerable controversy. To help resolve the issue we used a very specific and sensitive assay to compare photoreactivation activity in human, rattlesnake, yeast, and Escherichia coli cells. Photolyase was easily detectable in E. coli, yeast, and rattlesnake cell-free extracts but none was detected in cell-free extracts from HeLa cells or human white blood cells with an assay capable of detecting 10 molecules per cell. We conclude that humans most likely do not have DNA photolyase. PMID- 8506279 TI - The LIM motif defines a specific zinc-binding protein domain. AB - The cysteine-rich protein (CRP) contains two copies of the LIM sequence motif, CX2CX17HX2CX2CX2CX17-CX2C, that was first identified in the homeodomain proteins Lin-11, Is1-1, and Mec-3. The abundance and spacing of the cysteine residues in the LIM motif are reminiscent of a metal-binding domain. We examined the metal binding properties of CRP isolated from chicken smooth muscle (cCRP) and from a bacterial expression system and observed that cCRP is a specific Zn-binding metalloprotein. Four Zn(II) ions are maximally bound to cCRP, consistent with the idea that each LIM domain coordinates two metal ions. From spectroscopic studies of Co(II)- and 113Cd(II)-substituted cCRP, we determined that each metal ion is tetrahedrally coordinated with cysteinyl sulfurs dominating the ligand types. One metal site within each LIM motif has tetrathiolate (S4) coordination, the second site may either be S4 or S3N1. The LIM motif represents another example of a specific Zn-binding protein sequence. PMID- 8506281 TI - A proposal for a new approach to a preventive vaccine against human immunodeficiency virus type 1. AB - Human immunodeficiency virus type 1 (HIV-1) is a more complex retrovirus, coding for several accessory proteins in addition to the structural proteins (Gag, Pol, and Env) that are found in all retroviruses. More complex retroviruses have not been isolated from birds, and simpler retroviruses have not been isolated from humans. However, the proviruses of many endogenous simpler retroviruses are present in the human genome. These observations suggest that humans can mount a successful protective response against simpler retroviruses, whereas birds cannot. Thus, humans might be able to mount a successful protective response to infection with a simpler HIV-1. As a model, a simpler bovine leukemia virus which is capable of replicating has been constructed; a simpler HIV-1 could be constructed in a similar fashion. I suggest that such a simpler HIV-1 would be a safe and effective vaccine against HIV-1. PMID- 8506280 TI - Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. AB - Antigen receptor-stimulated cell death of developing, immature T cells plays an important role in shaping the repertoire of antigens to which mature T cells will respond, but a role for receptor-stimulated death in controlling responses of mature T cells is controversial. Mutant lpr/lpr mice exhibit an autoimmune syndrome similar to systemic lupus erythematosus. Here we demonstrate that these mice have a defect in antigen-stimulated suicide of activated T cells in mature CD4+ and CD8+ T cell compartments. The defective suicide pathway is evident when the T cells are stimulated with antigen on antigen-presenting cells or with immobilized anti-CD3 in the absence of antigen-presenting cells. These studies, in concert with the work of others, suggest that antigen-stimulated death of mature cells may be important both in establishing peripheral tolerance and in limiting inflammation during normal immune responses. PMID- 8506282 TI - In vivo evidence against the existence of antiprogestins disrupting receptor binding to DNA. AB - The binding of a steroid hormone to its receptor elicits a sequence of events: activation of the receptor (probably through dissociation from a complex of heat shock proteins), dimerization, binding to hormone responsive elements, and finally modulation of gene transcription. RU 486, the first antiprogestin studied, has been shown to act at the last step of this sequence: provoking an inefficient binding of the receptor to hormone responsive elements. Recently, based on in vitro studies, it has been proposed that ZK 98299 was the prototype of a second class of antiprogestins that were supposed to act through disruption of the binding to DNA. We have devised methods allowing us to study the various steps of agonist or antagonist action in vivo. We show here that RU 486 and ZK 98299 have the same effects on receptor activation, dimerization, and binding to hormone responsive elements; differences in their action are explained by the 10 fold difference in their affinity for the receptor (ZK 98299 having the lower affinity). PMID- 8506283 TI - Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate. AB - Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcellular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5 alpha dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate. PMID- 8506284 TI - Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils. AB - We synthesized polypeptides corresponding to sequences encoded by normal and mutant alleles in the regions of codon 178 (Asp-->Asn) and codon 200 (Glu-->Lys) of the chromosome 20 amyloid gene that have been linked to familial Creutzfeldt Jakob disease. Peptide suspensions from both regions spontaneously formed amyloid fibrils with different morphological characteristics and aggregation tendencies. Fibrillar arrays were denser and more profuse in mutant than in normal peptide suspensions and were even more marked when the homologous mutant and normal peptides were mixed together. Preparations from the region of codon 200 were in all cases more fibrillogenic than corresponding peptides from the region of codon 178. These in vitro observations support the hypothesis that amino acid changes from pathogenic single-allele point mutations in Creutzfeldt-Jakob disease may nucleate the in vivo folding behavior of the normal host protein to favor formation of insoluble amyloid fibrils. PMID- 8506285 TI - In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. AB - The particle bombardment method of gene transfer provides an alternative approach for analysis of in vivo promoter activity and transgene expression. Transient expression of the firefly luciferase gene from five viral and five cellular promoters was assessed after in vivo gene transfer using this method. The relative strengths of these promoters were quantitatively determined in five different rat tissues: skin epidermis, dermis, muscle, liver, and pancreas. Cytomegalovirus immediate early enhancer/promoter activity was consistently the highest in each tissue, whereas other promoters displayed tissue-specific preferences. In liver, the mouse phosphoenolpyruvate carboxykinase and metallothionein promoters were stimulated in vivo by inducing agents at 1 and 5 days posttransfection. In dermis, sustained luciferase activity was observed for over 1.5 years after gene delivery. In vivo transgene expression was also detected in bombarded mouse, rabbit, and rhesus monkey tissues. These results suggest that particle bombardment provides an effective system for studies of in vivo gene transfer and gene therapy. PMID- 8506286 TI - Extrathymic differentiation of T lymphocytes and natural killer cells from human embryonic liver precursors. AB - Liver cells were isolated on Ficoll/Hypaque gradients from embryos or fetuses at 6-10 weeks of gestation; 2-20% of the cells expressed CD45 or HLA class I surface antigens and 2-6% expressed CD7. Other T- or natural-killer (NK)-cell-lineage specific markers were undetectable. Liver-cell suspensions cultured in the presence of phytohemagglutinin and recombinant interleukin 2 gave rise to large proportions of CD3+ lymphocytes expressing either alpha/beta or gamma/delta T cell receptors. This occurred not only in bulk cultures but also when cells were cloned under limiting dilution conditions. Importantly, these figures were obtained also in embryos at 6-8 weeks of gestation, which is before colonization of the thymic rudiment by T-cell precursors. When the same liver-cell suspensions were cultured in the presence of irradiated H9 cells and recombinant interleukin 2 (either in bulk cultures or under cloning conditions), large proportions of cells (or clones) expressed surface CD16 and CD56 antigens and displayed a strong cytolytic activity against both NK-sensitive (K562) and NK-resistant (M14) target cells. In addition, liver-derived T or NK cells expressed functional receptor molecules since they could be activated via either CD3/T-cell receptor or CD16 surface antigens, respectively. Further fractionation of liver cells on the basis of CD45 antigen expression indicated that only CD45+ cells could give rise to T or NK cells in culture. Thus, CD45 can be used as a marker for identification of an early liver-cell population containing T- and NK-cell precursors. That T or NK cells were derived from male embryos and not from the mother was shown by PCR amplification of X and Y chromosomal sequences. Our present data may offer an in vitro model for extrathymic embryonic T-cell maturation that can be used to examine fundamental aspects of human T-cell development and function. PMID- 8506287 TI - Oscillations in local field potentials of the primate motor cortex during voluntary movement. AB - We investigated the occurrence and distribution of oscillatory activity in local field potentials (LFPs) recorded from the frontal motor cortex of behaving monkeys performing skilled voluntary movements. LFPs were recorded simultaneously from up to 12 sites distributed throughout motor cortex while monkeys performed a visually guided, instructed delay task using the wrist or digits. Oscillatory activity between 15 and 50 Hz was evident in the LFP recorded from both primary motor cortex and premotor areas. Oscillations occurred preferentially before the visual cue to initiate movement but were infrequent during movement. Oscillations typically stopped before movement initiation during the wrist task, although they often continued into the initial phases of movement during the digit task. The relationship of oscillations to task performance was consistent across trials over periods of many months, although the amplitude and duration of oscillations varied across trials and days. Interactions between pairs of LFP recordings, evaluated with cross-correlation analysis, revealed synchronous oscillations over long distances (> 7 mm) and across primary motor cortex and premotor recording sites. These studies demonstrate that oscillations recorded in the LFP in motor cortex during trained motor tasks are not related to the details of movement execution but may be related to aspects of movement preparation. PMID- 8506288 TI - Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis. AB - The interaction of tumor necrosis factor alpha (TNF) with its two membrane-bound receptors initiates intracellular events in which arachidonic acid and its derivatives are involved. In HeLa cells, TNF treatment induces an arachidonic acid-selective, Ca(2+)-dependent cellular phospholipase A2 (cPLA2). By itself, TNF causes a modest increase in cPLA2 activity, but with the Ca2+ ionophore A23187 it provides a strong synergistic action. Within minutes in response to TNF, cPLA2 becomes phosphorylated and in the presence of Ca2+ produces a 3- to 4 fold increase in activity. TNF also increases cPLA2 mRNA and protein expression, an estimated 5-fold increase in an 8-hr period. This increase in cPLA2 activity occurs, therefore, in a biphasic time-dependent manner. Dexamethasone, known to antagonize the action of TNF, is here shown to inhibit TNF-induced gene expression and to prevent the second phase of increase in cPLA2 activation. Our results suggest that the cPLA2 activation may provide a regulatory function and may explain the proinflammatory action of TNF. PMID- 8506289 TI - Identification of human endogenous retroviruses with complex mRNA expression and particle formation. AB - Retroviruses comprise strains with considerable disease potential in animals and humans. In addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. Some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. They may also be considered as mobile genetic elements with the potential to produce mutations. In humans, genomic DNA contains numerous endogenous retroviral sequences detected by their partial relatedness to animal retroviruses. However, all proviruses sequenced so far have been found to be defective. In this communication, we describe the expression of a family of human endogenous retrovirus sequences (HERV-K) in GH cells, a teratocarcinoma cell line producing the human teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identified, including a full length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression pattern is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti- or spumavirus strains, although HERV-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed non-defective gag genes, a prerequisite for particle formation. Open reading frames were also observed in pol and env. Antisera raised against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family. PMID- 8506290 TI - Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. AB - Erythropoietin regulates the proliferation and differentiation of erythroid precursor cells. Its effect is mediated by the erythropoietin receptor (EPOR), a member of a large family of cytokine receptors. The EPOR gene has recently been cloned, sequenced, and characterized. As shown experimentally, its intracellular C-terminal part contains a domain exerting negative control on erythropoiesis. Here we describe a G to A transition in nucleotide 6002 of the EPOR gene that converts a TGG codon for tryptophan into a TAG stop codon, predicting the truncation of the 70 C-terminal amino acids of the EPOR molecule. The mutation occurs in heterozygous form in the germ-line DNA of members of a large kindred in which primary erythrocytosis is segregating as a mild autosomal dominant trait. The mutation cosegregates with the disease phenotype in all 29 affected family members studied; it occurs in no unaffected family members or unrelated controls. This appears to be an example of a human condition caused by an EPOR mutation. Striking similarities exist between the human phenotype described here and phenotypes of cell lines expressing similarly truncated EPOR molecules produced experimentally. By analogy with these in vitro studies, one can hypothesize that the truncated EPOR molecules are activated by suppression of phosphorylation leading to loss of the down-modulation exerted by intact EPOR molecules. Experimental modifications of the EPOR gene may eventually have therapeutic applications. PMID- 8506291 TI - Developmental gene expression and tissue distribution of the CHIP28 water-channel protein. AB - The CHIP28 water channel is a major component of red cell and renal tubule membranes; however, its ontogeny and tissue distribution remain undefined. Three patterns of expression were identified when CHIP28 mRNA was surveyed by in situ hybridization histochemistry in rats between embryonic day 14 and maturity. (i) CHIP28 mRNA and protein were very abundant in hematopoietic tissue and kidneys of mature rats, but strong expression did not occur until after birth, when it appeared in renal proximal tubules and descending thin limbs, red pulp of the spleen, and membranes of circulating red cells. (ii) CHIP28 mRNA was abundant in choroid plexus epithelium throughout fetal development and maturity. (iii) CHIP28 mRNA was transiently observed in periosteum, heart, vascular endothelium, and cornea during fetal development. The ontogeny of kidney and red cell CHIP28 expression coincides with the ability of kidneys to concentrate urine, suggesting that CHIP28 promotes water reabsorption in the proximal nephron and provides red cell osmoregulation needed for passage through the hypertonic medulla. Its presence in the choroid plexus suggests that CHIP28-mediated water transport contributes to secretion of cerebrospinal fluid. The functional role of CHIP28 in developing bone, heart, and eye is unclear. These findings further establish the general physiologic role of CHIP28 as a water channel involved in reabsorption, osmoregulation, and secretion. The studies also suggest other possible functions during fetal development and predict that complex mechanisms will be needed for regulation of CHIP28 gene expression in diverse tissues at distinct points in development. PMID- 8506292 TI - Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins. AB - The related AP-1 and ATF/CREB families of transcriptional regulatory proteins bind as dimers to overlapping or adjacent DNA half-sites by using a bZIP structural motif. Using genetic selections, we isolated derivatives of yeast GCN4 that affect DNA-binding specificity at particular positions of the AP-1 target sequence. In general, altered DNA-binding specificity results from the substitution of larger hydrophobic amino acids for GCN4 residues that contact base pairs. However, in several cases, DNA binding by the mutant proteins cannot be simply explained in terms of the GCN4-AP-1 structure; movement of the protein and/or DNA structural changes are required to accommodate the amino acid substitutions. The quintet of GCN4 residues that make base-pair contacts do not entirely determine DNA-binding specificity because these residues are highly conserved in the bZIP family, yet many of the bZIP proteins bind to distinct DNA sites. The alpha-helical fork between the GCN4 DNA-binding and dimerization surfaces is important for half-site spacing preferences, because mutations in the fork alter the relative affinity for AP-1 and ATF/CREB sites. The basic region in the protein-DNA complex is a long isolated alpha-helix, with no constraints from other parts of a folded domain. From all of these considerations, we suggest that small shifts in position and orientation or local deformations in the alpha helical backbone distinguish one bZIP complex from another. PMID- 8506293 TI - Systemic immunological effects of cytokine genes injected into skeletal muscle. AB - Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo. PMID- 8506294 TI - RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. AB - We describe a system to evaluate the function of lymphocyte-specific and generally expressed genes in the differentiation and/or function of lymphocytes. RAG-2 (recombination-activating gene 2)-deficient mice have no mature B and T lymphocytes due to the inability to initiate VDJ recombination. Blastocysts from RAG-2-deficient mice generate animals with no mature B and T cells following implantation into foster mothers. However, injection of normal ES cells into RAG 2-deficient blastocysts leads to the generation of somatic chimeras with mature B and T cells all of which derive from the injected ES cells (referred to as RAG-2 deficient blastocyst complementation). Complementation of RAG-2-deficient blastocysts with mutant ES cells heterozygous for a targeted mutation that deletes all immunoglobulin heavy-chain joining (JH) gene segments (JH+/-) also leads to generation of chimeras with normal B and T cells. However, complementation with ES cells homozygous for the JH mutation (JH-/-) generates animals with normal T cells but no B cells, due to a block in B-cell development at a very early stage. Transfection of a functionally assembled mu heavy-chain gene into the JH-/- ES cells prior to blastocyst injection rescues the JH-/- mutation and allows the generation of both mature T and mature B cells. The rescued B cells express IgM but not IgD and respond normally to bacterial lipopolysaccharide stimulation by proliferating and by secreting IgM. PMID- 8506295 TI - bcl-2 inhibits death of central neural cells induced by multiple agents. AB - The protooncogene bcl-2, which has been implicated in B-cell lymphoma development, inhibits apoptosis due to growth factor withdrawal in some, but not all, hematopoietic cells. Recently we found that bcl-2 also inhibits apoptosis in PC12 pheochromocytoma cells. We now report that bcl-2 inhibits the death of a central neural cell line due to serum and growth factor withdrawal, the calcium ionophore A23187, glucose withdrawal, membrane peroxidation, and, in some cases, free radical-induced damage. This broad range of protective effects of BCL-2 protein suggests that BCL-2 may interact with a central step in neural cell death. Measurements of intracellular free calcium suggest that BCL-2 alters the transduction of neural death signals at a point distal to the rise in intracellular free calcium. PMID- 8506296 TI - Isolation and expression of human 1,25-dihydroxyvitamin D3 24-hydroxylase cDNA. AB - Human 1,25-dihydroxyvitamin D3 24-hydroxylase cDNA clones were isolated from an HL-60 cell cDNA library by using a reverse transcription/polymerase chain reaction-generated human cDNA probe. The 24-hydroxylase cDNA consists of a 1539 bp open reading frame encoding a 513-amino acid polypeptide. Protein sequence analysis shows that the human 24-hydroxylase is 90% homologous (82% identical) to that of the rat, with 100% homology in the 21-amino acid heme-binding region. Northern blot analysis showed that the 24-hydroxylase cDNA probe hybridized to a 3.4-kb mRNA species. Treatment of HL-60 cells with 0.1 microM 1,25 dihydroxyvitamin D3 for 24 hr produced a 30-fold increase in the 24-hydroxylase mRNA level. This result is consistent with previous studies in the same cell line, in which 24-hydroxylase activity was elevated to a maximum in 24 hr by a similar treatment with 1,25-dihydroxyvitamin D3. To verify the identity of these isolated cDNA clones, two polymerase chain reaction-amplified human 24 hydroxylase cDNA fragments containing the entire coding region were used to produce 24-hydroxylase enzyme activity in two genetic expression systems. Transient levels of 24-hydroxylase activity were measured in transfected mammalian COS-1 cells and in recombinant baculovirus-infected Spodoptera frugiperda (Sf21) insect cells. PMID- 8506297 TI - Amino acid substitution at the Adh locus of Drosophila is facilitated by small population size. AB - The number of amino acid replacement substitutions and that of synonymous substitutions are examined by using DNA sequences of the Adh locus of Drosophila. The ratio of replacement to synonymous substitutions is higher in sequence comparisons between species than in polymorphisms within species. The ratio for the between-species comparisons is highest in the Hawaiian group and lowest in the obscura group. These observations suggest that amino acid substitutions are facilitated by small population size. The result is in accord with the nearly neutral theory of molecular evolution. PMID- 8506298 TI - Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. AB - Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is the second most common cause of congenital adrenal hyperplasia and results in a hypertensive form of the disease. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Two mutations in CYP11B1 have previously been reported in patients with 11 beta-hydroxylase deficiency--Arg-448 ->His and a 2-bp insertion in codon 394. We now report eight previously uncharacterized mutations causing this disorder. Seven are point mutations (three nonsense and four missense) and one is a single base pair deletion causing a frameshift. We have used an in vitro transfection assay to show that all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity. In principle, deletions of CYP11B1 could be generated by unequal crossing-over between CYP11B1 and the adjacent CYP11B2 gene, but no such deletions were found among the deficiency alleles in this study. Seven of the 10 known mutations are clustered in exons 6-8, a nonrandom distribution within the gene. This may reflect the location of functionally important amino acid residues within the enzyme or an increased tendency to develop mutations within this region of the gene. PMID- 8506299 TI - Methylation induced premeiotically in Ascobolus: coextension with DNA repeat lengths and effect on transcript elongation. AB - The effect of duplications of gene fragments on the triggering of DNA methylation induced premeiotically (MIP) was studied in the sexual progeny of strains harboring, in addition to the resident met2 gene, a fragment of this gene inserted at an ectopic position. Cytosine methylation of the resident gene was checked for each of the eight duplications tested. Methylation was always found and it was coextensive with the length of the duplications. Silencing of the resident gene was triggered by duplications of segments corresponding to the region 5' to the open reading frame, to only the open reading frame, or to segments beginning 0.87-1.2 kb downstream from the transcription start. Silencing was accompanied by either the absence of transcripts or the presence of truncated transcripts, which suggests that methylation acts on transcript elongation. PMID- 8506300 TI - Copper-controllable gene expression system for whole plants. AB - We describe a system for gene expression in plants based on the regulation mechanism of the yeast metallothionein (MT) gene. The system consists of two elements: (i) the yeast ace1 (activating copper-MT expression) gene encoding a transcription factor under control of the cauliflower mosaic virus (CaMV) 35S RNA promoter, and (ii) a gene of interest under control of a chimeric promoter consisting of the 90-base-pair domain A of the CaMV 35S RNA promoter linked to the ACE1 transcription factor-binding site. At elevated copper ion concentrations, the ACE1 protein changes conformation, binds to, and activates transcription from the chimeric promoter. To test the functioning of the system in plants, a construct containing the beta-glucuronidase (GUS) reporter gene under control of the chimeric promoter was prepared, and transgenic tobacco plants were produced. It was shown that GUS activity in the leaves of transgenic plants increased up to 50-fold, either after addition of 50 microM CuSO4 to the nutrient solution or after application of 0.5 microM CuSO4 to the plants in a foliar spray. This GUS expression was repressed after the removal of copper ions. The results show that the activity of the described chimeric promoter directly depends on copper ion concentration and that this system can be used in experiments that demand precise timing of expression. PMID- 8506301 TI - A gene for a low density lipoprotein receptor-related protein in the nematode Caenorhabditis elegans. AB - A >23-kb gene that encodes a large integral membrane protein with a predicted structure similar to that of the low density lipoprotein (LDL) receptor-related protein (LRP) of mammals has been isolated and sequenced from the free-living nematode Caenorhabditis elegans. The 4753-amino acid predicted C. elegans product shares a nearly identical number and arrangement of amino acid sequence motifs with human LRP, and several exons of the C. elegans LRP gene correspond to exons of related parts of the human LDL receptor gene. The existence of an apparent homolog of LRP in C. elegans offers the possibility of genetic analysis of the in vivo roles of LRP and of the relationship between protein structure and function in a simple model organism. PMID- 8506303 TI - Simple and efficient production of embryonic stem cell-embryo chimeras by coculture. AB - A method for the production of embryonic stem (ES) cell-embryo chimeras was developed that involves the simple coculture of eight-cell embryos on a lawn of ES cells. After coculture, the embryos with ES cells attached are transferred to normal embryo culture medium and allowed to develop to the blastocyst stage before reimplantation into foster mothers. Although the ES cells initially attach to the outside of the embryos, they primarily colonize the inner cell mass and its derivatives. This method results in the efficient production of chimeras with high levels of chimerism including the germ line. As embryos are handled en masse and manipulative steps are minimal, this method should greatly reduce the time and effort required to produce chimeric mice. PMID- 8506302 TI - Transforming growth factor beta enhances integrin expression and type IV collagenase secretion in human monocytes. AB - Transforming growth factor beta (TGF-beta), secreted within an inflammatory site or injected locally, induces leukocyte margination, chemotaxis, and accumulation. In addition to its potent direct chemotactic activity, TGF-beta may promote this leukocyte response by influencing cell surface integrin expression. At picomolar concentrations, TGF-beta increases steady-state mRNA levels for both the alpha 5 and the beta 1 chain of the fibronectin receptor in human blood monocytes. This increase in gene expression is reflected by selectively enhanced expression of alpha 5 (CDw49e), beta 1 (CDw29), and also alpha 3 (CDw49c) adhesion molecules on the cell surface. Functionally, TGF-beta promotes, in a dose- and time-dependent fashion, monocyte adhesion to type IV collagen, laminin, and fibronectin. Potentially facilitating the movement of monocytes through the extracellular matrix, TGF-beta triggers transcriptional and posttranscriptional regulation of both the 92-kDa and the 72-kDa gelatinase/type IV collagenase. Thus, TGF-beta may play a pivotal role in the early phases of inflammation and repair through its ability to mediate monocyte adhesion, chemotaxis, and enzymatic digestion of extracellular matrix, whereas in chronic lesions, excess TGF-beta may contribute to persistent leukocyte accumulation. PMID- 8506304 TI - Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear stress-responsive element. AB - The endothelial lining of blood vessels is constantly exposed to fluid mechanical forces generated by flowing blood. In vitro application of fluid shear stresses to cultured endothelial cells influences the expression of multiple genes, as reflected by changes in their steady-state mRNA levels. We have utilized the B chain of platelet-derived growth factor (PDGF-B) as a model to investigate the mechanisms of shear-stress-induced gene regulation in cultured bovine aortic endothelial cells (BAECs). Northern blot analysis revealed elevated endogenous PDGF-B transcript levels in BAECs, after exposure to a physiological level of laminar shear stress (10 dynes/cm2; 1 dyne = 100 mN) for 4 h. A transfected reporter gene, consisting of a 1.3-kb fragment of the human PDGF-B promoter coupled to chloramphenicol acetyltransferase (CAT), indicated a direct effect on transcriptional activity. Transfection of a series of PDGF-B-CAT deletion mutants led to the characterization of a cis-acting component within the PDGF-B promoter that was necessary for shear-stress responsiveness. In gel-shift assays, overlapping oligonucleotide probes of this region formed several protein-DNA complexes with nuclear extracts prepared from both static and shear-stressed BAECs. A 12-bp component (CTCTCAGAGACC) was identified that formed a distinct pattern of complexes with nuclear proteins extracted from shear-stressed BAECs. This shear-stress-responsive element does not encode binding sites for any known transcription factor but does contain a core binding sequence (GAGACC), as defined by deletion mutation in gel-shift assays. Interestingly, this putative transcription factor binding site is also present in the promoters of certain other endothelial genes, including tissue plasminogen activator, intercellular adhesion molecule 1, and transforming growth factor beta 1, that also are induced by shear stress. Thus, the expression of PDGF-B and other pathophysiologically relevant genes in vascular endothelium appears to be regulated, in part, by shear stress-induced transcription factors interacting with a common promoter element. PMID- 8506305 TI - Airway epithelial cells are the site of expression of a mammalian antimicrobial peptide gene. AB - We previously reported the isolation and characterization of a broad-spectrum antimicrobial peptide from the bovine tracheal mucosa, which we called tracheal antimicrobial peptide (TAP). We now show the TAP gene is expressed throughout the adult conducting airway, from nasal to bronchiolar tissue, but not in tissues other than airway mucosa, as determined by Northern blot analysis. In situ hybridization of airway sections localizes TAP mRNA to columnar cells of the pseudostratified epithelium. We report the structural organization of the TAP gene and show that TAP is a member of a large family of related sequences with high nucleotide identity in the 5' exon. The data support the hypothesis that antimicrobial peptides contribute to host defense of the respiratory tract. PMID- 8506306 TI - Secondary structure creates mismatched base pairs required for high-affinity binding of cAMP response element-binding protein to the human enkephalin enhancer. AB - Transactivation studies of the enkephalin enhancer indicate that two cAMP response elements (CRE-1 and CRE-2) are needed to mediate the transcriptional response to cAMP and to the CRE-binding protein (CREB) transcription factor. CRE 1 and CRE-2 are contained within a nearly palindromic region that can form stable hairpin structures in vitro. CREB binds only weakly to the native duplex enhancer and only within CRE-2. In contrast, CREB binds with high affinity to the hairpin in which CRE-1 and CRE-2 come together to form a CREB site with two G.T base pairs. NMR and binding studies show that high-affinity binding to the G.T hairpin requires one of the mismatched G.T pairs. Insertion of that G.T pair into the duplex confers high-affinity binding. Parallel studies with the somatostatin CRE show that the T in one G.T pair is crucial for high-affinity binding. The existence within a short enhancer of alternative sites for a single factor suggests a mechanism for regulation of transcription by DNA structure. PMID- 8506307 TI - In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells. AB - Coagulation factor IX is a serine protease for which high-level expression of biologically active protein in heterologous cells is limited due to inefficient proteolytic removal of the propeptide as well as vitamin K-dependent carboxylation of multiple amino-terminal glutamic acid residues. We have overexpressed the vitamin K-dependent gamma-carboxylase cDNA and monitored its ability to improve factor IX processing in Chinese hamster ovary (CHO) cells. From amino acid sequence analysis of bovine liver vitamin K-dependent gamma carboxylase, degenerate oligonucleotides were used to isolate a 3.5-kbp bovine cDNA that encoded a 758-residue open reading frame. Expression of the cDNA in COS 1 and CHO cells yielded 17- and 16-fold increases in the in vitro gamma carboxylase activity of microsomal preparations, respectively. Anti-serum raised against a predicted peptide sequence reacted with a 94-kDa polypeptide in the partially purified bovine liver preparation as well as in stably transfected CHO cells. The amount of antibody reactivity correlated with the increased ability to carboxylate a peptide substrate in vitro. These results strongly support the conclusion that the cDNA encodes the vitamin K-dependent gamma-carboxylase. Transient transfection of the gamma-carboxylase expression vector into factor IX expressing CHO cells did not improve the specific procoagulant activity of secreted factor IX. In contrast, transfection of an expression vector encoding the propeptide processing enzyme PACE (paired basic amino acid cleaving enzyme) did improve the specific activity of secreted factor IX by 3-fold. These results demonstrate that the ability of CHO cells to modify glutamic acid residues to gamma-carboxyglutamic acid in secreted factor IX is not limited by the expression of the vitamin K-dependent gamma-carboxylase alone. PMID- 8506308 TI - Detection and characterization of mammalian DNA polymerase beta mutants by functional complementation in Escherichia coli. AB - We have designed and utilized a bacterial complementation system to identify and characterize mammalian DNA polymerase beta mutants. In this complementation system, wild-type rat DNA polymerase beta replaces both the replicative and repair functions of DNA polymerase I in the Escherichia coli recA718 polA12 double mutant; our 263 DNA polymerase beta mutants replace E. coli polymerase I less efficiently or not at all. Of the 10 mutants that have been shown to contain DNA sequence alterations, 2 exhibit a split phenotype with respect to complementation of the growth defect and methylmethanesulfonate sensitivity of the double mutant; one is a null mutant. The mutants possessing a split phenotype contain amino acid residue alterations within a putative nucleotide binding site of DNA polymerase beta. This approach for the isolation and evaluation of mutants of a mammalian DNA polymerase in E. coli may ultimately lead to a better understanding of the mechanism of action of this enzyme and to precisely defining its role in vertebrate cells. PMID- 8506309 TI - Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. AB - Chromosome translocations involving band 11q23 are associated with human acute leukemias. These translocations fuse the ALL-1 gene, homolog of Drosophila trithorax and located at chromosome band 11q23, to genes from a variety of chromosomes. We cloned and sequenced cDNAs derived from transcripts of the AF-4 and AF-9 genes involved in the most common chromosome abnormalities, t(4:11)(q21:q23) and t(9:11)(p22:q23), respectively. Sequence analysis indicates high homology between the AF-9 gene protein product and the protein encoded by the ENL gene fused to ALL-1 in (11:19) chromosome translocations. AF-4, AF-9, and ENL proteins contain nuclear targeting sequences as well as serine-rich and proline-rich regions. Stretches abundant in basic amino acids are also present in the three proteins. These results suggest that the different proteins fused to ALL-1 polypeptide(s) provide similar functional domains. PMID- 8506310 TI - Phylogenetic analysis of rbcL sequences identifies Acorus calamus as the primal extant monocotyledon. AB - The identity of the oldest lineage of monocotyledons is a subject of debate. Alternative interpretations of morphological homologies are variously consistent with proposals that species of Alismatanae, Dioscoreales, or Melanthiales were the earliest descendants of the first monocotyledons. We present phylogenetic analyses based on DNA sequences of the plastid locus rbcL in which Acorus calamus, an herb with unspecialized floral features and of uncertain affinities, is supported as a member of the oldest extant lineage of monocotyledons. This conclusion is consistent with a substantial body of morphological, anatomical, and embryological evidence and offers an explanation for the failure to identify any close relationship between Acorus and other genera. PMID- 8506311 TI - Immunotherapy of malignancy by in vivo gene transfer into tumors. AB - The immune system confers protection against a variety of pathogens and contributes to the surveillance and destruction of neoplastic cells. Several cell types participate in the recognition and lysis of tumors, and appropriate immune stimulation provides therapeutic effects in malignancy. Foreign major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. In this report, a foreign MHC gene was introduced directly into malignant tumors in vivo in an effort to stimulate tumor rejection. In contrast to previous attempts to induce tumor immunity by cell-mediated gene transfer, the recombinant gene was introduced directly into tumors in vivo. Expression of the murine class I H-2Ks gene within the CT26 mouse colon adenocarcinoma (H-2Kd) or the MCA 106 fibrosarcoma (H-2Kb) induced a cytotoxic T-cell response to H-2Ks and, more importantly, to other antigens present on unmodified tumor cells. This immune response attenuated tumor growth and caused complete tumor regression in many cases. Direct gene transfer in vivo can therefore induce cell-mediated immunity against specific gene products, which provides an immunotherapeutic effect for malignancy, and potentially can be applied to the treatment of cancer and infectious diseases in man. PMID- 8506312 TI - Storage of a sensory pattern by anti-Hebbian synaptic plasticity in an electric fish. AB - Synaptic plasticity occurs in several regions of the vertebrate brain and is believed to mediate the storage of behaviorally significant information during learning. Synaptic plasticity is well demonstrated in most cases, but the behavioral meaning of the relevant neural signals and the behavioral role of the plasticity are uncertain. In this paper we describe a case of synaptic plasticity which involves identifiable sensory and motor signals and which appears to mediate the storage of an image of past sensory input. Corollary discharge signals associated with the motor command that drives the electric organ are prominent in the electrosensory lobe of mormyrid electric fish. Some of these corollary discharge signals elicit a negative image or representation of the electrosensory input pattern that has followed recent motor commands. When the temporal and spatial pattern of sensory input changes, the corollary discharge effect also changes in a corresponding manner. The cellular mechanisms by which the corollary discharge-evoked representation is stored were investigated by intracellular recording from cells of the electrosensory lobe and pairing intracellular current pulses with the corollary discharge signal. The results indicate that the representation of recent sensory input is stored by means of anti-Hebbian plasticity at the synapses between corollary discharge-conveying fibers and cells of the electrosensory lobe. The results also suggest that dendritic spikes and plasticity at inhibitory synapses are involved in the phenomenon. PMID- 8506313 TI - Molecular cloning of olfactomedin, an extracellular matrix protein specific to olfactory neuroepithelium. AB - The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. Here we describe the molecular cloning and primary structure of olfactomedin, which is the major component of this extracellular matrix. Olfactomedin is expressed exclusively in olfactory neuroepithelium and its amino acid sequence shows no homologies to any known protein. This olfactory tissue-specific glycoprotein contains cysteines which form disulfide-linked polymers that constitute the primary architecture of the olfactory extracellular matrix. By analogy to other extracellular matrix proteins of the nervous system, olfactomedin may influence the maintenance, growth, or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. PMID- 8506314 TI - Intracellular calcium increases with hyperactivation in intact, moving hamster sperm and oscillates with the flagellar beat cycle. AB - At some time before fertilization, mammalian sperm undergo a change in movement pattern, termed hyperactivation. There is evidence that hyperactivation offers an advantage to sperm for detaching from the oviductal mucosa, for penetrating viscoelastic substances in the oviduct, and for penetrating the zona pellucida. Hyperactivation is known to require extracellular calcium, but little else is known about the mechanisms by which calcium affects sperm movement. The calcium sensitive fluorescent dye indo-1 was used to follow intracellular calcium levels ([Ca2+]i) in individual moving sperm. Sperm were loaded with 10 microM of the acetoxymethyl ester form of the dye and then rinsed. The dye was excited at 340 nm by using a filtered xenon stroboscope, and images at the 405-nm and 490-nm excitation maxima were simultaneously digitized at 30 per sec for 2.1 sec. [Ca2+]i was significantly higher in the acrosomal and postacrosomal regions of the head and in the flagellar midpiece (the principal piece could not be measured) in hyperactivated than in nonhyperactivated sperm (P < 0.0001). [Ca2+]i oscillations were detected in the proximal half of the midpiece that were identical in frequency to the flagellar-beat-cycle frequency in 12 of 17 hyperactivated sperm (median, 3.5 Hz). Rapid [Ca2+]i oscillations were also detected in the acrosomal and postacrosomal regions, as well as in the distal midpiece. Oscillations were not eliminated by dampening the flagellar bending with methyl cellulose. The [Ca2+]i oscillations detected in sperm are significantly more rapid than oscillations detected in other cell types. PMID- 8506315 TI - Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. AB - We report experiments in the rat demonstrating the feasibility of intraventricular administration of oligodeoxynucleotides (ODNs) as a regional treatment approach to disorders within the central nervous system (CNS). Although we find little intrinsic nuclease activity in cerebrospinal fluid (CSF), phosphodiester ODNs are rapidly degraded by brain-associated alpha-exonuclease activity. Phosphorothioate ODNs, however, appear resistant to degradation in the CNS and, after intraventricular administration, we find they are cleared in a manner consistent with CSF bulk flow. Continuous infusion of ODN at 1.5 nmol/hr by miniosmotic pump can maintain micromolar concentrations of intact phosphorothioate ODN in CSF for at least 1 week without obvious neurologic or systemic toxicity. After infusion, extensive brain penetration and marked cellular uptake, especially by astrocytic cells, is demonstrated. PMID- 8506316 TI - Genetic evidence on origin and dispersal of human populations speaking languages of the Nostratic macrofamily. AB - Contemporary patterns of allele frequencies allow inferences on past evolutionary processes. L.L. CavalliSforza [(1988) Munibe 6, 129-137] and C. Renfrew [(1991) Cambridge Archaeol. J. 1, 3-23] proposed that neolithic farmers from the Near East propagated a group of related ancestral languages, from which three or four linguistic families developed. Here we show that genetic variation among Indo European, Elamo-Dravidian, and Altaic speakers (grouped by some linguists in the Nostratic macrofamily) supports this hypothesis, whereas the evidence on Afro Asiatic speakers is ambiguous. Gene-frequency clines within these linguistic families suggest that language diffusion was largely associated with population movements rather than with purely cultural transmission. Archeological, linguistic, and genetic evidence can be reconciled by envisaging a process of population growth and multidirectional dispersal from the Near East as the main factor shaping genetic and linguistic diversity in Eurasia and perhaps in North Africa. PMID- 8506317 TI - C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements. AB - Members of the C/EBP family of basic-leucine zipper (bZip) transcription factors form heterodimers and bind to the CAAT box and other sequence-related enhancer motifs. Using a 32P-labeled protein probe consisting of the bZip domain of C/EBP beta, we isolated a clone encoding C/EBP-related ATF (C/ATF), a bZip protein that heterodimerizes with C/EBP-like proteins but belongs to the CREB/ATF family. C/ATF homodimers do not bind to typical C/EBP DNA sites. Instead they bind to palindromic cAMP response elements such as that of the somatostatin gene. In addition, C/ATF-C/EBP beta heterodimers bind to a subclass of asymmetric cAMP response elements exemplified by those in the phosphoenolpyruvate carboxykinase and proenkephalin genes. Transient transfection studies indicate that interactions between C/ATF and C/EBP beta are the basis for a functional cross talk between these two families of transcription factors that may be important for the integration of hormonal and developmental stimuli that determine the expression of subsets of genes in specific cellular phenotypes. PMID- 8506318 TI - Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. AB - Here I show that nuclear extracts of chicken embryos can promote the active demethylation of DNA. The evidence shows that in hemimethylated DNA (i.e., methylated on one strand only) demethylation of 5mCpG occurs through nucleotide excision repair. The first step of demethylation is the formation of specific nicks 5' from 5-methyldeoxycytidine. Nicks are also observed in vitro on symmetrically methylated CpGs (i.e., methylated on both strands) but they result in breakage of the oligonucleotide with no repair. No specific nicks are observed on the nonmethylated CpG. Nicks are strictly 5mCpG specific and do not occur on 5mCpC, 5mCpT, 5mCpA, or 6mApT. The effect of nonspecific nuclease(s) has been ruled out. The nicking of mCpG takes place in the presence of 20 mM EDTA irrespective of the nature of the sequence surrounding the 5mCpG. No methylcytosine glycosylase activity could be detected. The repair is aphidicolin and N-ethylmaleimide resistant, suggesting a repair action by DNA polymerase beta. In extracts of chicken embryos, the excision repair of mCpG is highest between the 6th and the 12th day of development, whereas it is barely detectable in nuclear extracts from different organs of adults. The possible implications of 5mCpG endonuclease activity in active demethylation of DNA during differentiation is discussed. PMID- 8506319 TI - Postcopulatory sexual selection in an arctiid moth (Utetheisa ornatrix). AB - The offspring of twice-mated female Utetheisa ornatrix show low incidence of mixed paternity. Most progeny are sired exclusively by one male, the larger one, irrespective of parental age, male pyrrolizidine alkaloid content, mating order, between-mating interval, or duration of copulation. Data are presented suggesting that the female herself may exert control over the process by which one set of sperm is utilized at the expense of the other. Evidence for such postcopulatory female choice of sperm had not previously been obtained for an insect. Promiscuity provides the female with a means for accruing nuptial gifts (nutrients, defensive alkaloids). Sperm selection provides her with the option of utilizing sperm from larger, potentially more fit, males. PMID- 8506320 TI - Oxygen toxicity in a polyamine-depleted spe2 delta mutant of Saccharomyces cerevisiae. AB - When a mutant of Saccharomyces cerevisiae (spe2 delta) that cannot make spermidine or spermine was incubated in a polyamine-deficient medium in oxygen, there was a rapid cessation of cell growth and associated cell death. In contrast, when the mutant cells were incubated in the polyamine-deficient medium in air or anaerobically, the culture stopped growing more gradually, and there was no significant loss of cell viability. We also found that the polyamine deficient cells grown in air, but not those grown anaerobically, showed a permanent loss of functional mitochondria ("respiratory competency"), as evidenced by their inability to grow on glycerol as the sole carbon source. These data support the postulation that polyamines act, in part, by protecting cell components from damage resulting from oxidation. However, since the mutant cells still required spermidine or spermine for growth when incubated under strictly anaerobic conditions, polyamines must also have other essential functions. PMID- 8506321 TI - Tissue-specific versus cell type-specific expression of the glial fibrillary acidic protein. AB - Expression of the glial cell-specific gene encoding glial fibrillary acidic protein (GFAP) is regulated in a tissue-specific (neural tissue versus other tissues) as well as a cell type-specific (glial cell versus neuron) manner. Using a family of rat neurotumor RT4 cell lines in which neuronal/glial differentiation occurs in vitro, along with cell lines of different tissue origins, we identified by transient- and permanent-transfection assays two negative regulatory regions, GFAP downstream regulators 1 and 2 (GDR1 and GDR2). Both regions lie 3' of the transcription start site; GDR1 is in a 2.7-kb region extending from the first intron through the fifth exon, and GDR2 is within 1.7 kb 3' of the polyadenylylation site. GDR1 alone is responsible for tissue-specific expression (suppression in nonneural tissues), while both GDR1 and GDR2 are necessary for cell type-specific expression (suppression in neuronal cells). PMID- 8506322 TI - Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum. AB - Synthetic peptides patterned on the amino acid sequences found in two exofacial regions of band 3 protein (residues 824-829 of loop 7 and residues 547-553 of loop 3) blocked, in a dose-dependent fashion, the in vitro adherence of Plasmodium falciparum-infected erythrocytes to C32 amelanotic melanoma cells. Intravenous infusion of these synthetic peptides into Aotus and Saimiri monkeys infected with sequestering isolates of P. falciparum resulted in the appearance of mature forms of the parasite in the peripheral circulation. The finding that the peptides were effective as adhesion blockers in the micromolar range suggests that cerebral malaria could be managed through antiadhesion therapy. PMID- 8506323 TI - Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium. AB - CCRF-CEM is a human T-cell line originally isolated from a child with acute lymphoblastic leukemia. At cell densities > 2 x 10(5) cells per ml, CEM cells grow in serum-free medium, but at lower cell densities the cultures rapidly undergo apoptosis, or programmed cell death. The viability of low-density CEM cells could be preserved by supplementing the serum-free medium with "conditioned" medium from high-density CEM cultures, but a variety of known growth factors and lymphokines were ineffective. Fractionation of conditioned medium by sequential chromatography on DEAE-cellulose, propyl agarose, chromatofocusing, and hydrophobic-interaction HPLC resulted in the isolation of a 60-kDa protein capable of sustaining CEM growth in the absence of serum. The active protein was identified as human catalase based on its amino acid sequence and composition and was subsequently shown to exhibit catalase activity and to be replaceable by human erythrocyte catalase or bovine liver catalase. Comparison of the level of intracellular catalase activity with the amount released into the culture medium demonstrated that the latter accounted for < 3% of the total catalase activity present in the cell culture. These findings show that, despite its low amount, the catalase released by CEM cells, and perhaps by T cells in general, provides a critical first line of defense against hydrogen peroxide (H2O2) present in the extracellular milieu. PMID- 8506324 TI - Perturbations of the distal heme pocket in human myoglobin mutants probed by infrared spectroscopy of bound CO: correlation with ligand binding kinetics. AB - The infrared spectra of CO bound to human myoglobin and myoglobin mutants at positions His-64, Val-68, Asp-60, and Lys-45 on the distal side have been measured between 100 and 300 K. Large differences are observed with mutations at His-64 and Val-68 as well as with temperature and pH. Although distal His-64 is found to affect CO bonding, Val-68 also plays a major role. The variations are analyzed qualitatively in terms of a simple model involving steric interaction between the bound CO and the distal residues. A strong correlation is found between the final barrier height to CO recombination and the CO stretch frequency: as compared to wild type, the barrier is smaller in those mutants that have a higher CO stretch frequency (vCO) and vice versa. Possible reasons for this correlation are discussed. It is emphasized that the temperature and pH dependence of both the kinetics and the infrared spectra must be measured to obtain a consistent picture. PMID- 8506325 TI - Transfer RNAs with complementary anticodons: could they reflect early evolution of discriminative genetic code adaptors? AB - In accordance with the hypercycle theory of M. Eigen and P. Schuster [(1979) Hypercycle: A Principle of Natural Self-Organization (Springer, New York)], the ancestors of modern tRNAs appear to have emerged via the shortest possible way, both complementary strands of a short symmetrical double helix serving as pre tRNAs with complementary anticodons. This conclusion is based upon results of comparative sequence analysis of the 17-base-long anticodon loop and stem of tRNAs totaling 896 and especially of 22 pairs of consensus tRNAs with complementary or quasi-complementary anticodons. With regard to the anticodon loop and stem of pairs of consensus tRNAs, complementary distances were considerably less than direct distances--i.e., antiparallel pairing invariably yielded fewer mismatches than direct pairing. Furthermore, the smallest complementary distance was detected when two antiparallel sequences formed irregular G-U bonds in their anticodon triplets. The above implies that pre-tRNAs in peribiotic times were long hairpin structures having 73 bases or more, the middle base of an anticodon being the center of symmetry. Accordingly, each pair of pre-tRNAs with complementary anticodons should have been almost identical with each other except for their three central bases. The above situation appears to have dictated the early establishment of direct links between anticodons and the type of amino acids with which tRNAs are to be charged. This direct link is still maintained between modern aminoacyl-tRNA synthetases and anticodons. Replication of the double helices concertedly generated new codons for the same pair of amino acids. Thus, occurrence of synonymous as well as certain "palindromic" features of the genetic code table might have been determined by this mechanism. PMID- 8506326 TI - Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency. AB - We have previously reported that the T lymphocytes of a child with severe combined immunodeficiency are defective in the transcription of several lymphokine genes that include IL2, IL3, IL4, and IL5, which encode interleukins 2, 3, 4, and 5 (IL-2, -3, -4, and -5). To determine whether the defect in the patient's T lymphocytes involved a trans-acting factor common to the affected lymphokine genes, we examined the ability of nuclear factors from the patient's T lymphocytes to bind response elements present in the regulatory region of IL2. Nuclear factor NF-kB, activation protein 1 (AP-1), OCT-1, and NF-IL-2B binding activity were normal. In contrast, the binding of the nuclear factor of activated T cells (NF-AT) to its response element in the IL2 enhancer and to an NF-AT-like response element present in the IL4 enhancer was abnormal. To ascertain whether the abnormal NF-AT binding activity was related to an impaired function, we transfected patient and control T lymphocytes with constructs containing the reporter gene encoding chloramphenicol acetyl transferase (CAT) under the control of the entire IL2 regulatory region or of multimers of individual enhancer sequences. CAT expression directed by the IL2 regulatory region or by a multimer of the NF-AT-binding site was markedly lower in the patient relative to controls. In contrast, CAT gene expression directed by a multimer of the OCT-1 proximal (OCT-1p)-binding site was equivalent in patient and controls. These results indicate that an abnormality of/or influencing NF-AT may underlie the multiple lymphokine deficiency in this patient. PMID- 8506327 TI - Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule associated cationic antimicrobial protein chemotactic for monocytes. AB - CAP37 (cationic antimicrobial protein of molecular mass 37 kDa) is a multifunctional protein isolated from the granules of human neutrophils. It is antibiotic and chemotactic and binds lipopolysaccharide. A synthetic peptide, amino acid sequence NQGRHFCGGALIHARFVMTAASCFQ, based on residues 20-44 of CAP37 protein mimics its antibiotic and lipopolysaccharide binding action. Peptide 20 44, at the concentrations tested, has antibacterial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. The bactericidal action of the peptide was pH dependent, with maximum activity at pH 5.0 and pH 5.5 and decreased activity at pH 7.0. Various truncations, substitutions, and other modifications in the sequence deteriorate its activity. Free sulfhydryl groups and/or disulfide bridge formation are required for optimum antibiotic activity, since substitution of serines for, or alkylation of, cysteine residues 26 and 42 eliminates bactericidal activity. Evidently amino acids 20-44 represent an important, perhaps principal, antibacterial domain of CAP37. This peptide should provide new insight into the mechanism of antimicrobial activity of CAP37 and may serve as a model for new, useful, synthetic antibiotics. PMID- 8506328 TI - Structure and expression of the human trithorax-like gene 1 involved in acute leukemias. AB - The human trithorax-like gene 1 (Htrx1 gene) is disrupted in 11q23 translocations that are associated with acute leukemias. Sequencing of a partial human cDNA revealed an open reading frame encoding 1012 amino acids with extensive homology to the Drosophila trithorax protein, particularly in the zinc finger-like domains. Htrx1 gene appears to be unique in the human genome and has been conserved during evolution. Use of the human cDNA as a probe demonstrates that this gene is interrupted in both infant and adult acute myeloid (AML) and lymphoid (ALL) leukemia patients with 11q23 translocations. The structure of the Htrx1 gene around the breakpoints shows that this part of the human gene is interrupted by nine introns. As a result of the rearrangement, zinc finger domains are translocated in both ALL and AML patients. Expression studies reveal that the Htrx1 gene differentially expresses three transcripts within the normal lymphocyte cell lineage. PMID- 8506329 TI - Amyloid beta-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth. AB - Progressive deposition of amyloid beta-protein (A beta) in brain parenchyma and blood vessels is a characteristic feature of Alzheimer disease. Recent evidence suggests that addition of solubilized synthetic A beta to medium may produce toxic or trophic effects on cultured hippocampal neurons. Because soluble A beta may not accumulate in significant quantities in brain, we asked whether immobilized A beta peptide as a substrate alters neurite outgrowth from cultured rat peripheral sensory neurons. This paradigm may closely mimic the conditions in Alzheimer disease brain tissue, in which neurites contact insoluble, extracellular aggregates of beta-amyloid. We detected no detrimental effects of A beta substrate on neurite outgrowth. Rather, A beta in combination with low doses of laminin or fibronectin enhanced neurite out-growth from these neuronal explants. Our results suggest that insoluble A beta in the cerebral neuropil may serve as a neurite-promoting matrix, perhaps explaining the apparent regenerative response of neurites observed around amyloid plaques in Alzheimer disease. Moreover, in concert with the recent discovery of A beta production by cultured neurons, our data suggest that A beta plays a normal physiological role in brain by complexing with the extracellular matrix. PMID- 8506330 TI - Gating currents of the cloned delayed-rectifier K+ channel DRK1. AB - Gating currents of the cloned delayed-rectifier K+ channel DRK1 expressed in Xenopus oocytes were measured with the open-oocyte Vaseline-gap voltage-clamp technique. DRK1 gating charge had the following salient properties: (i) gating charge amplitude correlated positively with size of the expressed ionic K+ currents; (ii) the time integral of ON and OFF gating currents was similar, indicating charge conservation and lack of charge immobilization; (iii) the gating-charge activation curve was shallower and had a half-activation potential 15 mV more negative than the activation curve for K+ conductance; (iv) effective valence for the gating current was about two electronic charges per gating subunit; (v) for large depolarizations (to > 0 mV) prominent rising phases were observed during the ON and OFF gating charge, which appeared as shoulders in unsubtracted traces; (vi) for small depolarizing pulses (to < 0 mV) ionic-current activation and deactivation had time constants similar to ON and OFF gating current decay, respectively; (vii) negative prepulses made more prominent the ON rising phase and delayed ionic and gating currents. The results are consistent with a model for K+ channel activation that has an early slow and/or weakly voltage-dependent transition between early closed states followed by more voltage dependent transitions between later closed states and a final voltage-independent closed-open transition. PMID- 8506331 TI - Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation. PMID- 8506332 TI - Differential antagonism of Ras biological activity by catalytic and Src homology domains of Ras GTPase activation protein. AB - Ras p120 GTPase activation protein (GAP), a cytosolic protein, is a negative mediator and potential downstream effector of Ras function. Since membrane association is critical for Ras function, we introduced the Ras membrane targeting signal (a 19-residue peptide ending in CAAX, where C = cysteine, A = aliphatic amino acid, and X = any amino acid) onto the GAP N-terminal Src homology 2 and 3 and the C-terminal catalytic domains (designated nGAP/CAAX and cGAP/CAAX, respectively) to determine the role of membrane association in GAP function. cGAP/CAAX and full-length GAP/CAAX, but not GAP or nGAP/CAAX, exhibited potent growth inhibitory activity. Whereas both oncogenic and normal Ras activity were inhibited by cGAP/CAAX, nGAP/CAAX, despite lacking the Ras binding domain, inhibited the activity of oncogenic Ras without affecting the action of normal Ras. Altogether, these results demonstrate that membrane association potentiates GAP catalytic activity, support an effector function for GAP, and suggest that normal and oncogenic Ras possess different downstream interactions. PMID- 8506333 TI - Design superiority of palindromic DNA sites for site-specific recognition of proteins: tests using protein stitchery. AB - Using protein stitchery with appropriate attachment of cysteines linking to either C or N termini of the basic region of the v-Jun leucine zipper gene regulatory protein, we constructed three dimers--pCC, pCN, and pNN. All three bind specifically to the appropriately rearranged DNA recognition sites for v Jun: ATGAcgTCAT, ATGAcgATGA, and TCATcgTCAT, respectively (Kd, approximately 4 nM at 4 degrees C). Results of DNase I footprinting provide strong support for bent recognition helices in leucine zipper protein-DNA complexes. Comparison of the results for pCC and pNN with those for pCN shows the design superiority of palindromic sequences for protein recognition. PMID- 8506334 TI - Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium. AB - The human hormone-sensitive lipase (HSL) gene encodes a 786-aa polypeptide (85.5 kDa). It is composed of nine exons spanning approximately 11 kb, with exons 2-5 clustered in a 1.1-kb region. The putative catalytic site (Ser423) and a possible lipid-binding region in the C-terminal part are encoded by exons 6 and 9, respectively. Exon 8 encodes the phosphorylation site (Ser551) that controls cAMP mediated activity and a second site (Ser553) that is phosphorylated by 5'-AMP activated protein kinase. Human HSL showed 83% identity with the rat enzyme and contained a 12-aa deletion immediately upstream of the phosphorylation sites with an unknown effect on the activity control. Besides the catalytic site motif (Gly Xaa-Ser-Xaa-Gly) found in most lipases, HSL shows no homology with other known lipases or proteins, except for a recently reported unexpected homology between the region surrounding its catalytic site and that of the lipase 2 of Moraxella TA144, an antarctic psychrotrophic bacterium. The gene of lipase 2, which catalyses lipolysis below 4 degrees C, was absent in the genomic DNA of five other Moraxella strains living at 37 degrees C. The lipase 2-like sequence in HSL may reflect an evolutionarily conserved cold adaptability that might be of critical survival value when low-temperature-mobilized endogenous lipids are the primary energy source (e.g., in poikilotherms or hibernators). The finding that HSL at 10 degrees C retained 3- to 5-fold more of its 37 degrees C catalytic activity than lipoprotein lipase or carboxyl ester lipase is consistent with this hypothesis. PMID- 8506335 TI - Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae. AB - A wide spectrum of DNA lesions are repaired by the nucleotide-excision repair (NER) pathway in both eukaryotic and prokaryotic cells. We have developed a cell free system in Saccharomyces cerevisiae that supports NER. NER was monitored by measuring repair synthesis in DNA treated with cisplatin or with UV radiation. Repair synthesis in vitro was defective in extracts of rad1, rad2, and rad10 mutant cells, all of which have mutations in genes whose products are known to be required for NER in vivo. Additionally, repair synthesis was complemented by mixing different mutant extracts, or by adding purified Rad1 or Rad10 protein to rad1 or rad10 mutant extracts, respectively. The latter observation demonstrates that the Rad1 and Rad10 proteins directly participate in the biochemical pathway of NER. NER supported by nuclear extracts requires ATP and Mg2+ and is stimulated by polyethylene glycol and by small amounts of whole cell extract containing overexpressed Rad2 protein. The nuclear extracts also contain base-excision repair activity that is present at wild-type levels in rad mutant extracts. This cell-free system is expected to facilitate studies on the biochemical pathway of NER in S. cerevisiae. PMID- 8506336 TI - Colocalization of centromeric and replicative functions on autonomously replicating sequences isolated from the yeast Yarrowia lipolytica. AB - Two sequences (ARS18 and ARS68) displaying autonomous replication activity were previously cloned in the yeast Yarrowia lipolytica. The smallest fragment (1-1.3 kb) required for extrachromosomal replication of a plasmid is significantly larger in Y. lipolytica than in Saccharomyces cerevisiae. Neither autonomously replicating sequence (ARS) is homologous with known ARS or centromere (CEN) consensus sequences. They share short regions of sequence similarity with each other. These ARS fragments also contain Y. lipolytica centromeres: (i) integration of marker genes at the ARS loci results in a CEN-linked segregation of the markers, (ii) an ARS on a plasmid largely maintains sister chromatid attachment in meiosis I, and (iii) integration of these sequences at the LEU2 locus leads to chromosome breakage. Deletions performed on ARS18 show that CEN and ARS functions can be physically separated, but both are needed to establish a replicating plasmid. PMID- 8506337 TI - Gene amplification in Rhizobium: identification and in vivo cloning of discrete amplifiable DNA regions (amplicons) from Rhizobium leguminosarum biovar phaseoli. AB - A genetic element that allows the positive selection of different genomic rearrangements was used to analyze DNA amplification in Rhizobium leguminosarum biovar phaseoli. Discrete amplifiable DNA regions (amplicons) were detected in different regions of the genome of the model strain CFN42, including the chromosome and several large plasmids. Amplicons were mobilized into Escherichia coli using a genetic approach that involves the introduction of an origin of replication active in E. coli and an origin of conjugal transfer into the amplifiable DNA regions of the Rhizobium genome. The strategy can be a valuable tool for studies on genome organization and function. We propose that amplicons define a structural characteristic of the genome that may play an important biological role. PMID- 8506338 TI - Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. AB - Antigens in extracellular fluids can be processed and presented with major histocompatibility complex (MHC) class I molecules by a subset of antigen presenting cells (APCs). Chicken egg ovalbumin (Ova) linked to beads was presented with MHC class I molecules by these cells up to 10(4)-fold more efficiently than soluble Ova. This enhanced presentation was observed with covalently or noncovalently linked Ova and with beads of different compositions. A key parameter in the activity of these conjugates was the size of the beads. The APC that is responsible for this form of presentation is a macrophage. These cells internalize the antigen constructs through phagocytosis, since cytochalasin B inhibited presentation. Processing of the antigen and association with MHC class I molecules appears to occur intracellularly as presentation was observed under conditions where there was no detectable release of peptides into the extracellular fluids. When injected in vivo in C57BL/6 mice, Ova-beads, but not soluble Ova, primed CD4- CD8+ cytotoxic T lymphocytes (CTLs). Similar results were obtained in BALB/c mice immunized with beta-galactosidase-beads. The implications of these findings for development of nonliving vaccines that stimulate CTL immunity are discussed. PMID- 8506339 TI - Elevated glucose and angiotensin II increase 12-lipoxygenase activity and expression in porcine aortic smooth muscle cells. AB - The lipoxygenase (LO) pathway of arachidonate metabolism has been suggested to play a key role in atherosclerosis and in mediating several actions of angiotensin II (AII). However, the relationship between LO activation and factors linked to accelerated diabetic vascular disease such as hyperglycemia and AII is not known. We have investigated the effect of high glucose (HG; 25 mM) and AII on LO activity as well as LO protein and mRNA expression in porcine aortic vascular smooth muscle cells (PVSMCs). We observed that cells cultured in HG had significantly higher levels of the cell-associated LO products 12- and 15 hydroxyeicosatetraenoic acids (HETEs). AII added to cells grown in HG specifically further increased only cell-associated 12-HETE levels. Using immunoblot analysis and reverse transcriptase PCRs, we demonstrated the presence in PVSMCs of porcine leukocyte-type 12-LO protein and mRNA, respectively. Furthermore, the levels of both were markedly upregulated by AII as well as by HG. These studies suggest that enhanced 12-LO activity and expression are mechanisms for accelerated vascular disease produced by HG and AII in diabetes mellitus. PMID- 8506340 TI - Echo-planar magnetic resonance imaging studies of frontal cortex activation during word generation in humans. AB - Nine subjects were studied by high-speed magnetic resonance imaging while performing language-based tasks. Subjects were asked either to repeat or to generate verbs associated with nouns read by an experimenter while magnetic resonance images were obtained of the left inferior frontal lobe. The echo-planar imaging sequence was used with a gradient echo time of 70 ms to give an apparent transverse relaxation time weighting (T2* that is sensitive to local hemoglobin levels. Images were acquired every 3 s (repetition time) in series of 32. In plane resolution was 6 x 4.5 mm and slice thickness was 10 mm. An increase in signal accompanied performance of the tasks, with significantly more activation for verb generation than for repeating. The activation effect occurred within 3 s after task onset and could be observed in single images from individual subjects. The primary focus of activation appeared in gray matter along a sulcus anterior to the lateral sulcus that included the anterior insula, Brodmann's area 47, and extending to area 10. Little or no activation of this region was found for a passive listening, covert generation, or mouth-movement control tasks. Significant activation was also found for a homologous region in the right frontal cortex but not for control regions in calcarine cortex. These results are consistent with prior studies that have used positron emission tomography imaging with 15O-labeled water as a blood flow tracer. PMID- 8506341 TI - Nouns and verbs are retrieved with differently distributed neural systems. AB - In a task designed to elicit the production of verbs, the patients known as AN 1033 and Boswell consistently produced the correct target words, performing no differently from normal controls. However, in a similar task designed to elicit the production of nouns, both patients performed quite defectively, and their scores were many SDs below those of controls. Language processing was otherwise normal--i.e., there were no impairments in grammar, morphology, phonetic implementation, or prosody; reading and writing were normal. In a third patient (KJ-1360), we obtained the reverse outcome--i.e., retrieval of common and proper nouns was preserved, but verb retrieval was defective. Together, the findings in the three patients constitute a double dissociation between noun and verb retrieval. In AN-1033 and Boswell, the lesions are located outside the so-called language areas (left frontoparietal operculum, posterior temporal region, inferior parietal lobule), where damage is associated with aphasia. The region of damage shared by the two patients is in left anterior and middle temporal lobe. This sector of left hemisphere contains systems for the retrieval of nouns that denote concrete entities. We propose that those systems are not essential for the retrieval of verbs and not involved in the vocal implementation of word forms. Those systems perform a two-way lexical-mediation role for concrete nouns and promote the reconstruction of a word form after the processing of sensory-motor characteristics of the entity denoted by that word. The findings in patient KJ 1360, whose lesion is in left premotor cortex, suggest that equivalent mediation systems for verbs are located in the left frontal region. PMID- 8506342 TI - p53 gene mutations and protein accumulation in human ovarian cancer. AB - Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal mullerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb1801. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer. PMID- 8506343 TI - Axonal sprouting and laminin appearance after destruction of glial sheaths. AB - Laminin, a large extracellular matrix molecule, is associated with axonal outgrowth during development and regeneration of the nervous system in a variety of animals. In the leech central nervous system, laminin immunoreactivity appears after axon injury in advance of the regenerating axons. Although studies of vertebrate nervous system in culture have implicated glial and Schwann cells as possible sources, the cells that deposit laminin at sites crucial for regeneration in the living animal are not known. We have made a direct test to determine whether, in the central nervous system of the leech, cells other than ensheathing glial cells can produce laminin. Ensheathing glial cells of adult leeches were ablated selectively by intracellular injection of a protease. As a result, leech laminin accumulated within 10 days in regions of the central nervous system where it is not normally found, and undamaged, intact axons began to sprout extensively. In normal leeches laminin immunoreactivity is situated only in the basement membrane that surrounds the central nervous system, whereas after ablation of ensheathing glia it appeared in spaces through which neurons grew. Within days of ablation of the glial cell, small mobile phagocytes, or microglia, accumulated in the spaces formerly occupied by the glial cell. Microglia were concentrated at precisely the sites of new laminin appearance and axon sprouting. These results suggest that in the animal, as in culture, leech laminin promotes sprouting and that microglia may be responsible for its appearance. PMID- 8506344 TI - Functional heterogeneity of calcium release by inositol trisphosphate in single Purkinje neurones, cultured cerebellar astrocytes, and peripheral tissues. AB - Purkinje neurones of the cerebellar cortex are rich in receptors for the Ca mobilizing second messenger inositol trisphosphate (InsP3) in association with intracellular Ca stores. Cytosolic Ca ions are important in regulating neuronal excitability but it has proved difficult to demonstrate InsP3-evoked release of Ca in mammalian central neurones directly. Intracellular release of InsP3 by flash photolysis of caged InsP3, combined with whole-cell patch clamp and microspectrofluorimetry of Ca indicators, allows comparison of InsP3-evoked Ca release in single Purkinje cells in cerebellar slices with the same process in cultured astrocytes and peripheral tissues. In astrocytes, hepatocytes, exocrine cells, and vascular endothelium, minimal Ca release from stores requires photorelease of InsP3 at concentrations of 0.2-0.5 microM, and maximal efflux as judged by the rate of increase of Ca concentration is seen with 5-10 microM InsP3. In contrast in Purkinje cells, InsP3 concentrations of > or = 9 microM were required to produce minimal Ca release from stores under the same conditions, and Ca efflux increased with InsP3 concentrations up to 70-80 microM. Furthermore, the rate of increase and size of the Ca concentration in Purkinje cells are 10- to 30-fold greater than in astrocytes and peripheral tissues. The InsP3 sensitivity was not affected by changing exogenous cytosolic Ca buffering, suggesting that endogenous Ca binding cannot account for the difference. The results show a functional difference in InsP3-evoked Ca release between Purkinje cells and peripheral tissues. PMID- 8506345 TI - Differentiation and identification of the two catalytic metal binding sites in bovine lens leucine aminopeptidase by x-ray crystallography. AB - The tightly binding and readily exchanging metal binding sites in the active site of bovine lens leucine aminopeptidase (blLAP; EC 3.4.11.1) have been differentiated and identified by x-ray crystallography. In native blLAP,Zn2+ occupies both binding sites. In solution, site 1 readily exchanges Zn2+ for other divalent cations, including Mg2+. The Zn2+ in site 2 is unavailable for metal exchange under conditions which allow exchange at site 1. The Zn2+/Mg2+ metal hybrid of blLAP (Mg-blLAP) was prepared in solution and crystallized. X-ray diffraction data to 2.9-A resolution were collected at -150 degrees C from single crystals of Mg-blLAP and native blLAP. Comparisons of omit maps calculated from the Mg-blLAP data with analogous maps calculated from the native blLAP data show electron density in one of the metal binding sites in Mg-blLAP which is much weaker than the electron density in the other binding site. Since there are fewer electrons associated with Mg2+ than with Zn2+, the difference in electron density between the two metal binding sites is consistent with occupancy of the weaker electron density site by Mg2+ and identifies this metal binding site as site 1, defined as the readily exchanging site. The present identification of the metal binding sites reverses the previous presumptive assignment of the metal binding sites which was based on the structure of native blLAP [Burley, S. K., David, P. R., Sweet, R. M., Taylor, A. & Lipscomb, W. N. (1992) J. Mol. Biol. 224, 113 140]. According to the residue-numbering convention of native blLAP, the new assignment of the metal binding sites identifies the readily exchanging site 1 with Zn-488, which is within interaction distance of one side-chain carboxylate oxygen from each of Asp-255, Asp-332, and Glu-334 and the main-chain carbonyl oxygen of Asp-332. The more tightly binding site 2 is identified with Zn-489, which is within interaction distance of one side-chain carboxylate oxygen from each of Asp-255, Asp-273, and Glu-334 and the side-chain amine nitrogen of Lys 250. PMID- 8506346 TI - Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. AB - A rapid method for the identification of known proteins separated by two dimensional gel electrophoresis is described in which molecular masses of peptide fragments are used to search a protein sequence database. The peptides are generated by in situ reduction, alkylation, and tryptic digestion of proteins electroblotted from two-dimensional gels. Masses are determined at the subpicomole level by matrix-assisted laser desorption/ionization mass spectrometry of the unfractionated digest. A computer program has been developed that searches the protein sequence database for multiple peptides of individual proteins that match the measured masses. To ensure that the most recent database updates are included, a theoretical digest of the entire database is generated each time the program is executed. This method facilitates simultaneous processing of a large number of two-dimensional gel spots. The method was applied to a two-dimensional gel of a crude Escherichia coli extract that was electroblotted onto poly(vinylidene difluoride) membrane. Ten randomly chosen spots were analyzed. With as few as three peptide masses, each protein was uniquely identified from over 91,000 protein sequences. All identifications were verified by concurrent N-terminal sequencing of identical spots from a second blot. One of the spots contained an N-terminally blocked protein that required enzymatic cleavage, peptide separation, and Edman degradation for confirmation of its identity. PMID- 8506347 TI - Single amino acid substitution affects desensitization of the 5-hydroxytryptamine type 3 receptor expressed in Xenopus oocytes. AB - 5-Hydroxytryptamine type 3 receptors were expressed in Xenopus oocytes from a cloned cDNA. The peak inward current evoked by 5-hydroxytryptamine (30 microM) was linearly related to the holding potential (-100 to +20 mV) and reversed near 0 mV. The inward current (at -60 mV) declined during the continued presence of 5 hydroxytryptamine with a half-time of about 2 s; this desensitization was 20 times slower in calcium-free solution. Desensitization was markedly different in channels in which Leu286 was changed by site-directed mutagenesis; this residue is thought to lie near the middle of the M2 segment. Desensitization was faster with Phe, Tyr, or Ala in this position and slower with Thr. Phe and Thr substitutions in the equivalent position of the nicotinic acetylcholine receptor have similar effects on desensitization, suggesting that the underlying conformational change might be common to ligand-gated channels. PMID- 8506348 TI - Modulation of the interaction between G-actin and thymosin beta 4 by the ATP/ADP ratio: possible implication in the regulation of actin dynamics. AB - The interaction of G-actin with thymosin beta 4 (T beta 4), the major G-actin sequestering protein in motile and proliferating cells, has been analyzed in vitro. T beta 4 is found to have a 50-fold higher affinity for MgATP-actin than for MgADP-actin. These results imply that in resting platelets and neutrophils, actin is sequestered by T beta 4 as MgATP-G-actin. Kinetic experiments and theoretical calculations demonstrate that this ATP/ADP dependence of T beta 4 affinity for G-actin can generate a mechanism of desequestration of G-actin by ADP, in the presence of physiological concentrations of T beta 4 (approximately 0.1 mM). The desequestration of G-actin by ADP is kinetically enhanced by profilin, which accelerates the dissociation of ATP from G-actin. Whether a local drop in the ATP/ADP ratio can allow local, transient desequestration and polymerization of actin either close to the plasma membrane, following platelet or neutrophil stimulation, or behind the Listeria bacterium in the host cell, while the surrounding cytoplasm contains sequestered ATP-G-actin, is an open issue raised by the present work. PMID- 8506349 TI - Mutations in the larval foraging gene affect adult locomotory behavior after feeding in Drosophila melanogaster. AB - Previous studies have shown a correlation between the locomotory component of larval and adult foraging behavior in the fruit fly. Here we show that this relationship is far more than mere correlation. It can be attributable to different alleles at the same genetic locus of the behavioral gene foraging (for). The for gene offers us the unique opportunity to study the genetic basis and evolutionary significance of a naturally occurring behavioral polymorphism. Until now, only the effect of for on Drosophila melanogaster larval behavior was studied. Larvae with the rover allele (forR) move significantly more while eating during a set time period than those homozygous for the sitter alleles (fors). Here, we show that rover and sitter larval strains derived from nature differ in the distance adults walk after feeding per unit time and that this variation results from different alleles at the foraging locus, the very gene originally defined on the basis of larval behavior. We hypothesize that for may be involved in the way flies evaluate a food resource. PMID- 8506350 TI - The interaction of bride of sevenless with sevenless is conserved between Drosophila virilis and Drosophila melanogaster. AB - An inductive interaction between the sevenless (sev) transmembrane tyrosine kinase receptor and the bride of sevenless (boss) transmembrane ligand is required for the development of the R7 photoreceptor neuron in the compound eye of Drosophila melanogaster. The boss protein is proposed to contain a large N terminal extracellular domain, seven transmembrane segments, and a C-terminal cytoplasmic tail. The boss protein from Drosophila virilis (bossvir) retains strong amino acid identity with loss from D. melanogaster (bossmel): 73% identity in the N-terminal extracellular domain and 91% identity in the seven transmembrane domain, including the cytoplasmic tail. By using P-element-mediated DNA transformation, the bossmel and bossvir genes were shown to rescue the D. melanogaster boss1 mutation. The expression of bossvir protein in D. melanogaster is indistinguishable from that of bossmel protein. Noncoding sequences which may regulate boss expression were identified based on their conservation during evolution. The predicted sev protein from D. virilis (sevvir) was previously shown to be 63% identical to sev from D. melanogaster (sevmel). A chimeric gene, (sevvir/mel), encoding the extracellular domain of sevvir and the cytoplasmic domain of sevmel rescues the D. melanogaster sevd2 mutation through interaction with either bossvir or bossmel. PMID- 8506351 TI - Histones H1 and H5 interact preferentially with crossovers of double-helical DNA. AB - The interaction of the linker histones H1 and H5 from chicken erythrocyte chromatin with pBR322 was studied as a function of the number of superhelical turns in circular plasmid molecules. Supercoiled plasmid DNA was relaxed with topoisomerase I so that a population with a narrow distribution of topoisomers, containing from zero to five superhelical turns, was obtained. None of the topoisomers contained alternative non-B-DNA structures. Histone-DNA complexes formed at either 25 or 100 mM NaCl final concentration and at histone-DNA molar ratios ranging from 10 to 150 were analyzed by agarose gel electrophoresis. The patterns of disappearance of individual topoisomer bands from the gel were interpreted as an indication of preference of the linker histones for crossovers of double-helical DNA. This preference was observed at both salt concentrations, being more pronounced under conditions of low ionic strength. Isolated H5 globular domain also caused selective disappearance of topoisomers from the gel, but it did so only at very high peptide-DNA molar ratios. The observed preference of the linker histones for crossovers of double-helical DNA is viewed as a part of the mechanism involved in the sealing of the two turns of DNA around the histone octamer. PMID- 8506352 TI - The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. AB - Tau is a neuronal phosphoprotein whose expression is developmentally regulated. A single tau isoform is expressed in fetal human brain but six isoforms are expressed in adult brain, with the fetal isoform corresponding to the shortest of the adult isoforms. Phosphorylation of tau is also developmentally regulated, as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer disease, the six adult tau isoforms become abnormally phosphorylated and form the paired helical filament, the major fibrous component of the characteristic neurofibrillary lesions. We show here that Ser-202 (in the numbering of the longest human brain tau isoform) is a phosphorylation site that distinguishes fetal from adult tau and we identify it as one of the abnormal phosphorylation sites in Alzheimer disease. The abnormal phosphorylation of tau at Ser-202 in Alzheimer disease thus recapitulates normal phosphorylation during development. PMID- 8506353 TI - Three-dimensional structures of avidin and the avidin-biotin complex. AB - The crystal structures of a deglycosylated form of the egg-white glycoprotein avidin and of its complex with biotin have been determined to 2.6 and 3.0 A, respectively. The structures reveal the amino acid residues critical for stabilization of the tetrameric assembly and for the exceptionally tight binding of biotin. Each monomer is an eight-stranded antiparallel beta-barrel, remarkably similar to that of the genetically distinct bacterial analog streptavidin. As in streptavidin, binding of biotin involves a highly stabilized network of polar and hydrophobic interactions. There are, however, some differences. The presence of additional hydrophobic and hydrophilic groups in the binding site of avidin (which are missing in streptavidin) may account for its higher affinity constant. Two amino acid substitutions are proposed to be responsible for its susceptibility to denaturation relative to streptavidin. Unexpectedly, a residual N-acetylglucosamine moiety was detected in the deglycosylated avidin monomer by difference Fourier synthesis. PMID- 8506354 TI - Transgenic mice expressing the tumor marker germ cell alkaline phosphatase: an in vivo tumor model for human cancer antigens. AB - We have generated a series of transgenic mouse lines harboring the entire human germ cell alkaline phosphatase (GCAP) gene linked to progressively longer sequences of flanking DNA. A 450-bp promoter sequence directs the expression of GCAP to the intestine and endothelial cells, while a 5' sequence of 1.7 kb directs GCAP expression to the spermatogenic lineage and to the eight-cell through the blastocyst stage of preimplantation development. The expression of GCAP in these FVB/N transgenic mice induces a cellular immune tolerance to GCAP. When mouse fibrosarcoma MO4 cells (C3H derived), stably transfected with the cloned GCAP gene, were injected s.c. in nontransgenic control (C3H x FVB/N) hybrid mice, GCAP-positive tumor cells were rejected. However, when GCAP expressing transgenic (C3H x FVB/N) hybrid mice were challenged with these cells, GCAP-positive tumors developed. Tumors also developed in the transgenic hybrid mice upon injection of MO4 cells transfected with the highly homologous placental alkaline phosphatase (PLAP) cDNA in spite of the presence in PLAP of 10 amino acids that are different from the corresponding residues in GCAP. These GCAP transgenic mice will allow the study of the immune response associated with the repeated administration of conjugated or derivatized anti-GCAP and anti-PLAP monoclonal antibodies. They will also enable evaluation of the therapeutic potential of bifunctional antibodies for T-cell recruitment and destruction of GCAP/PLAP-producing tumor cells. PMID- 8506355 TI - Chaos and the evolution of cooperation. AB - The "iterated prisoner's dilemma" is the most widely used model for the evolution of cooperation in biological societies. Here we show that a heterogeneous population consisting of simple strategies, whose behavior is totally specified by the outcome of the previous round, can lead to persistent periodic or highly irregular (chaotic) oscillations in the frequencies of the strategies and the overall level of cooperation. The levels of cooperation jump up and down in an apparently unpredictable fashion. Small recurrent and simultaneous invasion attempts (caused by mutation) can change the evolutionary dynamics from converging to an evolutionarily stable strategy to periodic oscillations and chaos. Evolution can be twisted away from defection, toward cooperation. Adding "generous tit-for-tat" greatly increases the overall level of cooperation and can lead to long periods of steady cooperation. Since May's paper [May, R. M. (1976) Nature (London) 261, 459-467], "simple mathematical models with very complicated dynamics" have been found in many biological applications, but here we provide an example of a biologically relevant evolutionary game whose dynamics display deterministic chaos. The simulations bear some resemblance to the irregular cycles displayed by the frequencies of host genotypes and specialized parasites in evolutionary "arms races" [Hamilton, W. D., Axelrod, R. & Tanese, R. (1990) Proc. Natl. Acad. Sci. USA 87, 3566-3573; Seger, J. (1988) Philos. Trans. R. Soc. London B 319, 541-555]. PMID- 8506356 TI - Molecular evolution of the Adh1 locus in the genus Zea. AB - We sampled DNA sequences from the locus encoding alcohol dehydrogenase 1 (alcohol:NAD+ oxidoreductase, EC 1.1.1.1). Our sample represents Adh1 alleles from a wide geographic distribution of Zea mays (maize) and two species of teosinte (Zea luxurians and Zea diploperennis). Using these and previously published sequences, we analyze the molecular evolution of Adh1 in the genus Zea. We perform tests to characterize recombination and identify the putative parents of the recombinant Adh1-Cm allele. We also perform tests for selection but are unable to detect either a selective sweep or strong balancing selection at the Adh1 locus. We estimate that divergence times between teosinte and some maize alleles are approximately 1 million years, whereas divergence times between distantly related maize alleles are approximately 2 million years. We conclude that the common ancestor to the genus Zea was polymorphic at the Adh1 locus. On the basis of previous estimates of nucleotide diversity at other maize loci, it appears that the common ancestor to the genus Zea was polymorphic at many loci. PMID- 8506357 TI - Studies on leukemia developing spontaneously in an inbred family of rats. AB - This study is a continuation of our recently reported observations on leukemia and lymphomas developing spontaneously in a subline of Sprague-Dawley rats bred by brother-to-sister mating in our laboratory. The previous preliminary report described our observations made in the course of the initial 12 generations of our leukemic subline. The current study reviews the data collected during 8 additional generations and results of experimental and morphologic studies. There was no problem in transmitting the spontaneously developing leukemia by inoculation of suspensions of leukemic cells into newborn or very young suckling Sprague-Dawley rats. Attempts to transmit the disease by inoculation of cell free, filtered leukemic extracts gave thus far positive results only in one experiment in which two of six inoculated rats developed leukemia and a third one developed an angiosarcoma on the neck. In six additional experiments, of a total of 37 rats inoculated with leukemic filtrates, none developed leukemia and 9 females developed mammary fibroadenomas. Reviews of microscopic slides of blood and of sections of lymphoid tumors, livers, spleens, kidneys, and fragments of bone marrow of the leukemic animals are discussed as well as electron microscopic studies. PMID- 8506358 TI - RNS2: a senescence-associated RNase of Arabidopsis that diverged from the S RNases before speciation. AB - Several self-compatible species of higher plants, such as Arabidopsis thaliana, have recently been found to contain S-like RNases. These S-like RNases are homologous to the S-RNases that have been hypothesized to control self incompatibility in Solanaceous species. However, the relationship of the S-like RNases to the S-RNases is unknown, and their roles in self-compatible plants are not understood. To address these questions, we have investigated the RNS2 gene, which encodes an S-like RNase (RNS2) of Arabidopsis. Amino acid sequence comparisons indicate that RNS2 and other S-like RNases make up a subclass within an RNase superfamily, which is distinct from the subclass formed by the S-RNases. RNS2 is most similar to RNase LE [Jost, W., Bak, H., Glund, K., Terpstra, P., Beintema, J. J. (1991) Eur. J. Biochem. 198, 1-6.], an S-like RNase from Lycopersicon esculentum, a Solanaceous species. The fact that RNase LE is more similar to RNS2 than to the S-RNases from other Solanaceous plants indicates that the S-like RNases diverged from the S-RNases prior to speciation. Like the S RNase genes, RNS2 is most highly expressed in flowers, but unlike the S-RNase genes, RNS2 is also expressed in roots, stems, and leaves of Arabidopsis. Moreover, the expression of RNS2 is increased in both leaves and petals of Arabidopsis during senescence. Phosphate starvation can also induce the expression of RNS2. On the basis of these observations, we suggest that one role of RNS2 in Arabidopsis may be to remobilize phosphate, particularly when cells senesce or when phosphate becomes limiting. PMID- 8506359 TI - An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholinesterase. AB - Electrostatic calculations based on the recently solved crystal structure of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) indicate that this enzyme has a strong electrostatic dipole. The dipole is aligned with the gorge leading to its active site, so that a positively charged substrate will be drawn to the active site by its electrostatic field. Within the gorge, aromatic side chains appear to shield the substrate from direct interaction with most of the negatively charged residues that give rise to the dipole. The affinity of quaternary ammonium compounds for aromatic rings, coupled with this electrostatic force, may work in concert to create a selective and efficient substrate-binding site in acetylcholinesterase and explain why the active site is situated at the bottom of a deep gorge lined with aromatic residues. PMID- 8506361 TI - Rapid identification of proteins. AB - The amino acid composition, molecular weight, and isoelectric point of a protein can all be easily and economically determined by current electrophoretic techniques. A method which uses such easily obtained data to identify proteins is described. A computer program first corrects for systematic errors in amino acid quantitation and then searches the current sequence database for proteins with amino acid compositions similar to the corrected values, taking into account the reliability of determination of each amino acid. The program also provides the calculated molecular weight, isoelectric point, and name of each candidate, providing three further independent criteria for protein identification. The program is surprisingly sensitive, and the composition data alone, if of good quality, usually suggest the correct protein as a strong candidate if it or a close homologue is present in the database. Further studies show that proteins in the current database have amino acid compositions distinct enough to allow this method to be generally applicable. The method is a quick and cost-effective first step in protein characterization and should become increasingly useful as the number of fully sequenced proteins continues to rise. PMID- 8506360 TI - Mutation of Asp74 of the rat angiotensin II receptor confers changes in antagonist affinities and abolishes G-protein coupling. AB - Aspartic acid in the second transmembrane domain is a highly conserved amino acid among the G protein-coupled receptors and is functionally important for agonist binding and G-protein coupling in beta 2-adrenergic and luteinizing hormone receptors. To determine whether this aspartic acid is also involved in the function of the rat vascular angiotensin II receptor subtype 1 (AT1a), Asp74 was replaced either by asparagine or by glutamic acid. When expressed in CHO cells, the two mutants and the wild-type receptor displayed similarly high affinities for the agonist [Sar1, Tyr(125I)4]angiotensin II [where Sar is sarcosine and Tyr(125I) is monoiodinated tyrosine] and the other agonists: ([Sar1]angiotensin II > angiotensin II > angiotensin III >> angiotensin I). However, the Asn74 mutant shows striking differences in its affinity for some antagonists when compared with the wild-type receptor: the affinity for DUP753 was decreased 10 fold, whereas it was increased 6-fold for [Sar1,Ala8]angiotensin II and 20-fold for CGP42112A. These pharmacological changes were associated with a major defect in transmembrane signaling, since angiotensin II was unable to stimulate inositol phosphate production and increase cytosolic Ca2+ concentration through the two mutated receptors, whereas a clear dose-dependent stimulation was observed in cells expressing the wild-type receptor. Angiotensin II was able to promote DNA synthesis through the wild type but not through the mutated receptors. These data indicate that the conserved Asp74 residue of the AT1a receptor is important for the binding of angiotensin II antagonists and is essential for the transmembrane signaling cascade. PMID- 8506362 TI - On the regeneration of the actin-myosin power stroke in contracting muscle. AB - The transient behavior of muscle in double-or multiple-step length perturbations [Lombardi, V., Piazzesi, G. & Linari, M. (1992) Nature (London) 355, 638-641] is simulated with a "conventional" cross-bridge model, which has been reported [Eisenberg, E., Hill, T. L. & Chen, Y. (1980) Biophys. J. 29, 195-227] to account for many mechanical, as well as biochemical, muscle data. The quick recovery of tension after double- or multiple-length perturbations was calculated for the model without any readjustment of its original parameters. The regeneration rate of the quick tension recovery of the model is fast and comparable to that measured experimentally by Lombardi et al. For multiple-step "stair-case"-type length releases, the tension response reaches a steady-state shape after three or four steps, and the average ATP turnover is much slower than the regeneration of the quick tension recovery. Our simulation shows that the experimental findings of Lombardi et al. can easily be reproduced by this simple conventional cross bridge model, in which the completion of one work-producing power stroke is coupled to the hydrolysis of one ATP molecule. Thus, to account for the data of Lombardi et al., there is no need to assume that cross-bridges can execute multiple power strokes per ATPase cycle, although cross-bridges may well be able to do so. The mechanism that underlies the fast regeneration of the quick tension recovery in the conventional model used here is discussed. PMID- 8506363 TI - Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube. AB - To study the process of ventricular specification during cardiogenesis, we examined the in situ expression of cardiac ventricular myosin light chain 2 (MLC 2v) mRNA during murine embryogenesis. As assessed by hybridization with a specific MLC-2v riboprobe, mRNA expression can be found in the ventricular region at day 8.0 postcoitum (pc). MLC-2v expression is high in the ventricular portion of the heart tube, with no detectable expression in the atrial or sinus venosus regions. The proximal outflow tract of the heart tube also expresses MLC-2v mRNA at minimally detectable levels at this time but then displays a temporally and spatially distinct pattern with expression well established in the proximal out flow tract region adjacent to the ventricular segment by days 9-10 pc, eventually reaching levels comparable to the trabeculated ventricular myocardium. By day 11 pc, prior to the completion of septation, expression then becomes restricted to the ventricular region at and below the level of the atrioventricular cushion. Transgenic mice harboring a 250-base-pair MLC-2v promoter fragment fused to a luciferase reporter gene demonstrate reporter gene activity from at least day 9 pc. Ventricular region-restricted expression of the luciferase reporter in the embryonic heart, as assessed by immunofluorescence and direct assay of reporter activity in microdissected atrial and ventricular muscle specimens, was confirmed from at least day 15 pc on. Taken together, this provides evidence for early positional specification of MLC-2v gene expression in the primitive heart tube and indicates regional specification of part of the ventricular muscle gene program can precede ventricular septation during mammalian cardiogenesis. Since the 250-base-pair promoter fragment is active developmentally in transgenic mice, this establishes it as a molecular target for the process of ventricular specification in the developing heart tube. PMID- 8506364 TI - Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck. AB - Ser-42 and Ser-59 in the N-terminal region have been identified as the major phorbol ester-induced phosphorylation sites of p56lck. Phosphorylation of Ser-59 results in a gel shift from 56 kDa to 61 kDa. Simultaneous phosphorylation of Ser 42 and Ser-59 results in a further gel shift to 63 kDa. In vitro kinase assays show that Ser-59 can be uniquely phosphorylated by mitogen-activated protein kinase and that Ser-42 can be phosphorylated by either protein kinase A or protein kinase C. PMID- 8506365 TI - Identification of two missense mutations in a dihydrolipoamide dehydrogenase deficient patient. AB - The molecular basis of dihydrolipoamide dehydrogenase (E3; dihydrolipoamide:NAD+ oxidoreductase, EC 1.8.1.4) deficiency in an E3-deficient patient was studied. Fibroblasts cultured from the patient contained only approximately 6% of the E3 activity of cells from a normal subject. Western and Northern blot analyses indicated that, compared to control cells, the patient's cells had a reduced amount of protein but normal amounts of E3 mRNA. Direct sequencing of E3 cDNA derived from the patient's RNA as well as each of the subclones of the cDNA revealed that the patient had two substitution mutations in the E3 coding region. One mutation changed a single nucleotide from A to G, resulting in substitution of Glu (GAA) for Lys-37 (AAA). The other point mutation was a nucleotide change from C to T, resulting in the substitution of Leu (CTG) for Pro-453 (CCG). These mutations appear to be significant in that they alter the active site and possibly the binding of FAD. PMID- 8506366 TI - Release of amyloid beta-protein precursor derivatives by electrical depolarization of rat hippocampal slices. AB - Proteolytic processing of the beta-amyloid protein precursor (APP) is regulated by cell-surface receptors. To determine whether neurotransmitter release in response to neuronal activation regulates APP processing in brain, we electrically depolarized superfused rat hippocampal slices and measured soluble APP derivatives released into the superfusate. Electrical depolarization caused a rapid increase in the release of both neurotransmitters and amino-terminal APP cleavage products. These derivatives lacked the APP carboxyl terminus and were similar to those found in both cell culture media and human cerebrospinal fluid. Superfusate proteins including lactate dehydrogenase were not changed by electrical depolarization. The release of amino-terminal APP derivatives increased with increasing stimulation frequencies from 0 to 30 Hz. The increased release was inhibited by the sodium-channel antagonist tetrodotoxin, suggesting that action-potential formation mediates the release of large amino-terminal APP derivatives. These results suggest that neuronal activity regulates APP processing in the mammalian brain. PMID- 8506367 TI - Azamacrolides: a family of alkaloids from the pupal defensive secretion of a ladybird beetle (Epilachna varivestis). AB - Defensive droplets from glandular hairs of the pupa of the Mexican bean beetle, Epilachna varivestis, contain a group of structurally novel alkaloids, the azamacrolides. The major constituent of this secretion, epilachnene, is shown to be (5Z)-11-propyl-12-azacyclotetradec-5-en-14-olide. The secretion also contains an epilachnadiene and trace amounts of three closely related components. PMID- 8506368 TI - Direction of microtubule movement is an intrinsic property of the motor domains of kinesin heavy chain and Drosophila ncd protein. AB - The kinesin heavy chain and the ncd (non-claret disjunctional) gene product of Drosophila are microtubule-associated motor proteins related by sequence similarity within an approximately 340-aa domain. Despite the sequence similarity, the kinesin heavy chain and ncd protein move in opposite directions on microtubules. To investigate the molecular basis for direction of movement, we created a series of truncated kinesin heavy chain and ncd proteins. We found that the conserved domain of both proteins has microtubule motor activity, although the efficiency with which ATP hydrolysis is coupled to microtubule movement declines dramatically with increasing truncation. Further, the direction of movement is intrinsic to the conserved motor domains, rather than being a consequence of domain organization or adjacent sequences. PMID- 8506369 TI - Identification of a binding site for the human immunodeficiency virus type 1 nucleocapsid protein. AB - The nucleocapsid (NC) protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is important for encapsidation of the virus genome, RNA dimerization, and primer tRNA annealing in vitro. Here we present evidence from gel mobility-shift experiments indicating that NCp7 binds specifically to an RNA sequence. Two complexes were identified in native gels. The more slowly migrating complex contained two RNA molecules and one peptide, while the more rapidly migrating one is composed of one RNA and one peptide. Further, mutational analysis of the RNA shows that the predicted stem and loop structure of stem-loop 1 plays a critical role. Our results show that NCp7 binds to a unique RNA structure within the psi region; in addition, this structure is necessary for RNA dimerization. We propose that NCp7 binds to the RNA via a direct interaction of one zinc-binding motif to stem-loop 1 followed by binding of the other zinc-binding motif to stem-loop 1, stem-loop 2, or the linker region of the second RNA molecule, forming a bridge between the two RNAs. PMID- 8506370 TI - 5'-CGA sequence is a strong motif for homo base-paired parallel-stranded DNA duplex as revealed by NMR analysis. AB - The structure of the non-self-complementary DNA heptamer d(CGACGAC) at low pH has been determined by the quantitative NMR refinement procedure designated SPEDREF (SPEctral-Driven REFinement). Acid-base titration of the molecule indicated a prominent n = 2 pKa near 6.8. In the pH range up to 6.0, the heptamer forms a remarkably stable double helix, which was conclusively shown to be an unusual homobase-paired parallel-stranded double helix (termed II-DNA). In this II-DNA helix, the 5'-CGA trinucleotide is the structural motif that accounts for the stability, with the C+-C hemiprotonated base pair (in which C+ is N3-protonated cytosine) providing for the alignment site and the unusual interstrand G-A base stack in the GpA step furnishing the additional stabilizing forces. The exchangeable proton data from two-dimensional nuclear Overhauser effect spectroscopy are in total agreement with the refined structure. We conclude that the 5'-CGA or other related sequences (e.g., 5'-CCGA) are powerful motifs in promoting the II-DNA or II-RNA conformations that may play certain biological functions. PMID- 8506371 TI - Transfection of the malaria parasite and expression of firefly luciferase. AB - The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes. PMID- 8506372 TI - Control of dorsoventral patterning of somitic derivatives by notochord and floor plate. AB - We have examined the effect of implantation of a supernumerary notochord or floor plate on dorsoventral somitic organization. We show that notochord and floor plate are able to inhibit the differentiation of the dorsal somitic derivatives- i.e., axial muscles and dermis--thus converting the entire somite into cartilage, which normally arises only from its ventral part. We infer from these results that the dorsoventral patterning of somitic derivatives is controlled by signals provided by ventral axial structures. PMID- 8506373 TI - Picosecond infrared studies of the dynamics of the photosynthetic reaction center. AB - The changes in the vibrational transitions of the protein and redox cofactors of the photosynthetic reaction center were examined by picosecond infrared spectroscopy. The spectra in the vibrational mid-infrared region (1800-1550 cm-1) of hydrated and partially dehydrated reaction centers were investigated from 50 ps to 4 ns after photoinitiation of the electron transfer. Features in the infrared difference spectra were identified with both protein and redox cofactor vibrational modes and correlated with electron transfer events whose kinetics were measured in the infrared and visible regions. The observed protein response is confined to a few amide I transitions (1644 cm-1, 1661 cm-1, 1665 cm-1) and carboxylic residues (1727 cm-1). About 85% of the observed signal corresponded to alterations in the cofactor-associated ester and keto carbonyls. The amide I and carboxylic transitions appeared prior to 50 ps, suggesting that the primary electron transfer event is coupled with a specific piece of the protein backbone and to glutamic or aspartic residues nearby the special pair. Infrared absorption changes accompanying bacteriochlorophyll-dimer cation formation dominated the signal at all times investigated. Infrared spectral changes observed in hydrated and partially dehydrated reaction centers were distinctly different; a band at 1665 cm-1 with a spectral width of 6 cm-1 in the hydrated protein, corresponding to a protein amide I bleach, was not present in the dehydrated film. These differences are discussed in terms of the markedly different electron transfer kinetics observed in the presence of water. PMID- 8506374 TI - Structural changes in the actomyosin cross-bridges associated with force generation. AB - It is generally thought that to generate active force in muscle, myosin heads (cross-bridges) that are attached to actin undergo large-scale conformational changes. However, evidence for conformational changes of the attached cross bridges associated with force generation has been ambiguous. In this study, we took advantage of the recent observation that cross-bridges that are weakly attached to actin in a relaxed muscle are apparently in attached preforce generating states. The experimental conditions were chosen such that there were large fractions of cross-bridges attached under relaxing and activating conditions, and high-resolution equatorial x-ray diffraction patterns obtained under these conditions were compared. Changes brought about by activation in the two innermost intensities, I10 and I11, did not follow the familiar reciprocal changes. Instead, there was almost no change in I11, whereas I10 decreased by 34%. Together with the changes found in the higher-order reflections, the results suggest that the structure of the attached force-generating cross-bridges differs from that of the weakly bound, preforce-generating cross-bridges and possibly also differs from that of the cross-bridges in rigor. These observations support the concept that force generation involves a transition between distinct structural states of the actomyosin cross-bridges. PMID- 8506375 TI - Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas. AB - Chromosomal translocations involving chromosome 3, band q27, are among the most common rearrangements in B-cell non-Hodgkin lymphoma. From a bacteriophage lambda library prepared from a lymphoma characterized by a t(3;14)(q27;q32), genomic clones were isolated using a probe from the immunoglobulin heavy chain locus (IGH) joining region. In addition to clones containing an apparently normal IGH rearrangement, others were found to contain one of the translocation breakpoint junctions. Normal chromosome 3 sequences and the reciprocal breakpoint junction were subsequently isolated. DNA probes on each side of the chromosome 3 breakpoint hybridized at high stringency to the DNA of various mammalian species, demonstrating evolutionary conservation. One such probe from the presumptive der(3) chromosome detected an 11-kilobase transcript when hybridized to RNA of B- and T-cell lines. A probe made from partial cDNA clones isolated from a T-cell line hybridized with genomic DNA from both sides of the chromosome 3 breakpoint, indicating that the t(3;14) is associated with a break within the gene on chromosome 3. In situ chromosomal hybridization revealed that the same gene is involved in the t(3;22)(q27;q11). Preliminary nucleotide sequencing shows no identity of the cDNA to gene sequences in available data banks. We propose the name BCL6 (B-cell lymphoma 6) for this gene, since it is likely to play a role in the pathogenesis of certain B-cell lymphomas. PMID- 8506376 TI - Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors. AB - MEF-2 is a muscle-specific DNA binding activity that recognizes an A+T-rich sequence found in the control regions of numerous muscle-specific genes. The recent cloning of MEF-2 showed that it belongs to the MADS (MCM1, Agamous, Deficiens, and serum-response factor) box family of transcription factors and that MEF-2 mRNA is expressed ubiquitously. Here we describe the cloning of a member of the MEF-2 gene family, referred to as MEF-2C, that is nearly identical to other MEF-2 gene products in the MADS box but diverges from other members of the family outside of this domain. MEF-2C binds the MEF-2 site with high affinity and can activate transcription of a reporter gene linked to tandem copies of that site. In contrast to previously described members of the MEF-2 family, MEF-2C transcripts are highly enriched in skeletal muscle, spleen, and brain of adult mice and are upregulated during myoblast differentiation. These results suggest that the MEF-2 site is a target for a diverse family of proteins that regulates transcription in a variety of cell types. PMID- 8506377 TI - Isolation and the complete amino acid sequence of lumenal endoplasmic reticulum glucose-6-phosphate dehydrogenase. AB - I have isolated glucose-6-phosphate dehydrogenase from rabbit liver microsomes and determined its complete amino acid sequence. Sequence determination was achieved by automated Edman degradation of peptides generated by chemical and enzymatic cleavages. The microsomal enzyme consists of 763 residues and is quite dissimilar from the previously characterized cytosolic enzymes. The N terminus of the microsomal enzyme is blocked by a pyroglutamyl residue. Carbohydrate is attached at Asn-138 and Asn-263, implying that the bulk of the protein is oriented on the lumenal side of the endoplasmic membrane. The amino acid sequence of the microsomal protein shows limited homology to the extensively sequenced cytosolic glucose-6-phosphate dehydrogenases. Clusters of up to six identical residues can be identified in four regions: peptide segments at residues 10-21, 154-163, and 173-261. In addition, another array of identical residues, requiring a 100-residue deletion in the sequence of the microsomal enzyme, spans residues 436-462 and corresponds to residues 348-373 of the cytosolic protein. Two segments with a Gly-Xaa-Gly-Xaa-Xaa-Gly motif, related to a coenzyme binding fold, were identified at Gly-399 and Gly-491. In the cytosolic enzymes, a variation of this sequence motif occurs at Gly-37 and Gly-241. The 300-residue C terminal segment of the microsomal enzyme is unique and has no counterpart in the cytosolic or the bacterial enzymes. An unexpected finding with regard to the microsomal enzyme is that it lacks an identifiable membrane-spanning region or the lumenal-protein C-terminal consensus sequences Lys-Asp-Glu or His-Ile/Thr-Glu Leu. Thus, the mode of transport and retention of this protein in the lumen of endoplasmic reticulum remains to be determined. PMID- 8506378 TI - Probability of DNA knotting and the effective diameter of the DNA double helix. AB - During the random cyclization of long polymer chains, knots of different types are formed. We investigated experimentally the distribution of knot types produced by random cyclization of phage P4 DNA via its long cohesive ends. The simplest knots (trefoils) predominated, but more complex knots were also detected. The fraction of knots greatly diminished with decreasing solution Na+ concentration. By comparing these experimental results with computer simulations of knotting probability, we calculated the effective diameter of the DNA double helix. This important excluded-volume parameter is a measure of the electrostatic repulsion between segments of DNA molecules. The calculated effective DNA diameter is a sensitive function of electrolyte concentration and is several times larger than the geometric diameter in solutions of low monovalent cation concentration. PMID- 8506379 TI - A highly polymorphic microsatellite in the class II Eb gene allows tracing of major histocompatibility complex evolution in mouse. AB - A hallmark of major histocompatibility complex (MHC) genes is their extraordinarily high level of polymorphism. Polymorphic residues on MHC molecules determine which peptide ligands they bind and present to effector T lymphocytes. Although the genetic mechanisms responsible for MHC polymorphism have been delineated, the timetable and the pathway of their diversification remain unclear. To trace MHC evolution, we have characterized a highly polymorphic microsatellite containing tandem repeats (TRs) of two tetranucleotide units, TGGA and GGCA, located at the 3' end of the second intron in the class II Eb gene of mouse. On the basis of length as well as sequence variations, 11 TR alleles were defined in 55 inbred mouse strains, which included MHC recombinant haplotypes and haplotypes derived from different subspecies of mouse. In this extensive sampling, a striking concordance was observed between the serologically identified class II proteins and the associated TR alleles. Examination of several strains carrying the same MHC haplotypes as well as strains carrying recombinant MHC haplotypes indicates that TR alleles are extremely stable. These observations suggest that TR polymorphism predates the separation of various subspecies of mouse. On the basis of sequence divergence, a genealogical tree has been constructed to depict evolution of the different TR alleles. Finally, evidence is presented that suggests this microsatellite polymorphism is generated by slipped-strand mispairing during DNA replication. PMID- 8506381 TI - Isolation of a proline-rich mycobacterial protein eliciting delayed-type hypersensitivity reactions only in guinea pigs immunized with living mycobacteria. AB - Effective protection against a virulent challenge with Mycobacterium tuberculosis is induced only by a previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guerin (BCG). Living and killed bacteria share a number of common antigens. To identify and to purify molecules that are dominant antigens during immunization with living bacteria, a two-step selection procedure was used. Quantitative delayed-type hypersensitivity (DTH) reactions elicited in guinea pigs immunized either with living or with killed BCG were used to select or counterselect antigens present in BCG culture filtrates. Each major fraction eluted from a series of HPLC columns (gel filtration, DEAE, reverse-phase chromatography) was assayed and titrated on guinea pigs of each group. A protein with an unusual amino acid composition (40% proline, 12% threonine) was purified and N-terminally sequenced. To our knowledge, the sequence Thr-Pro-Pro-Xaa-Glu Xaa-Pro-Pro-Pro-Pro-Gln-Xaa-Val-Xaa-Leu has not been previously reported. The protein was 100-fold more potent on guinea pigs immunized with living bacteria than on guinea pigs immunized with dead bacteria to elicit a DTH reaction. PMID- 8506380 TI - A gamma-aminobutyric acid transporter driven by a proton pump is present in synaptic-like microvesicles of pancreatic beta cells. AB - A variety of peptide-secreting endocrine cells contain a population of recycling microvesicles that share several major membrane polypeptides with neuronal synaptic vesicles (SVs). The function of these synaptic-like microvesicles (SLMVs) remains to be elucidated. It was previously suggested that SLMVs of pancreatic beta cells may store and secrete gamma-aminobutyric acid (GABA). GABA, the major nonpeptide inhibitory neurotransmitter of the central nervous system, is stored in and secreted from SVs. GABA uptake into SVs is mediated by a transporter that is driven by a vacuolar proton ATPase. GABA is also present at high concentration in the endocrine pancreas where it is selectively localized in insulin-secreting beta cells, the core cells of pancreatic islets. GABA is not present in peripheral islet cells (mantle cells), represented primarily by glucagon-secreting alpha cells. In this study, an immunoisolation procedure was used to purify SLMVs from cell lines derived from mouse beta cells and alpha cells. SLMVs obtained from the beta-cell line, but not those obtained from the alpha-cell line, displayed a GABA-transport activity dependent upon a proton electrochemical gradient generated by a vacuolar proton ATPase. These data support the hypotheses that (i) SLMVs have a secretory function similar to that of SVs and (ii) beta-cell SLMVs are involved in the secretion of GABA, which in turn may have a paracrine function on mantle cells of the islet. PMID- 8506382 TI - Prodrug activation via catalytic antibodies. AB - Prodrug activation via antibodies was examined by using the antibiotic chloramphenicol as a model drug. Based on the conformational change between substrate and product, this antibody-catalyzed reaction was designed to prevent product inhibition, thus enhancing turnover. Antibodies elicited against a phosphonate transition-state analogue were found to catalyze hydrolysis of a nonbioactive chloramphenicol monoester as a prodrug at a significantly higher rate above the uncatalyzed background reaction to regenerate chloramphenicol as a parent molecule. The antibody-catalyzed prodrug activation was tested by the paper-disc diffusion method using Bacillus subtilis as an indicator strain. The antibody 6D9 catalyzes the reaction with multiple turnover to generate enough chloramphenicol to inhibit bacterial growth, as indicated by a clear inhibitory zone after incubation with monoester. Using the same method, no inhibition was detected by incubation of either the monoester or the antibody alone. This result reveals that only the antibody hydrolytically activates the monoester, which can be expected to be a suitable prodrug, as it is resistant to the action of bacterial hydrolytic enzymes. The approach in this study demonstrates the use of catalytic antibody technology in medicine and may be applicable to drugs with undesirable effects, particularly in the field of cancer therapy. PMID- 8506383 TI - DNA interstrand cross-links of trans-diamminedichloroplatinum(II) are preferentially formed between guanine and complementary cytosine residues. AB - Bases in the opposite strands of DNA cross-linked by clinically ineffective trans diamminedichloroplatinum(II) (trans-[Pt(NH3)2Cl2]) have been identified by means of three experimental approaches. These include HPLC analysis of enzymatic digests of synthetic oligonucleotide duplexes containing the interstrand cross link, footprinting experiments on the interstrand cross-linked oligonucleotide duplexes, and termination of the duplex transcription on trans-[Pt(NH3)2Cl2] treated fragments of plasmid DNA. The results reveal that deoxyguanine and complementary deoxycytosine residues are preferential binding sites of trans [Pt(NH3)2Cl2] in the interstrand adducts. The interstrand cross-linking reaction was studied by means of gel electrophoresis for the cis and trans isomers. The rate of formation of interstrand cross-links was lower for the trans isomer; however, trans-[Pt(NH3)2Cl2] formed about twice the amount of interstrand cross links as compared with the cis isomer after 48 hr. The present results are suggested to be relevant to differences in clinical activity of the two platinum(II) isomers. PMID- 8506384 TI - A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast. AB - In Saccharomyces cerevisiae, phosphorylation of the alpha subunit of translation initiation factor 2 (eIF-2) by protein kinase GCN2 stimulates translation of GCN4 mRNA. In mammalian cells, phosphorylation of eIF-2 alpha inhibits the activity of eIF-2B, the GDP-GTP exchange factor for eIF-2. We present biochemical evidence that five translational regulators of GCN4 encoded by GCD1, GCD2, GCD6, GCD7, and GCN3 are components of a protein complex that stably interacts with eIF-2 and represents the yeast equivalent of eIF-2B. In vitro, this complex catalyzes guanine nucleotide exchange on eIF-2 and overcomes the inhibitory effect of GDP on formation of eIF-2.GTP.Met-initiator tRNA(Met) ternary complexes. This finding suggests that mutations in GCD-encoded subunits of the complex derepress GCN4 translation because they mimic eIF-2 alpha phosphorylation in decreasing eIF-2B activity. Our results indicate that translational control of GCN4 involves a reduction in eIF-2B function, a mechanism used in mammalian cells to regulate total protein synthesis in response to stress. PMID- 8506385 TI - The beta subunit of the mitochondrial processing peptidase from rat liver: cloning and sequencing of a cDNA and comparison with a proposed family of metallopeptidases. AB - Most nuclearly encoded mitochondrial proteins are synthesized with amino-terminal leader peptides that are removed by the mitochondrial processing peptidase (MPP) after translocation. Earlier we reported cloning and sequencing of a cDNA for the larger subunit (MPP alpha subunit) of this enzyme from rat liver mitochondria. We have now completed the cloning and sequencing of a cDNA encoding the smaller subunit of the enzyme (MPP beta subunit) from the same source. The cDNA consists of 1570 bp: 17 bp of 5'-untranslated sequence, 1467 bp of coding sequence, and 86 bp of 3'-untranslated sequence. The predicted protein consists of 489 amino acid residues, including a 45-amino acid leader peptide at the amino terminus and a 444-amino acid mature protein. The amino acid sequences of four tryptic peptides derived from purified MPP beta subunit precisely match those predicted by the cDNA sequence, as does the predicted mature amino terminus. The amino-terminal sequence is typical of a mitochondrial leader peptide, with eight positively charged arginine residues and a single negatively charged aspartate residue. When the amino acid sequence of rat MPP beta subunit is compared with sequences in the protein data bases, significant homology is found with the protease-enhancing protein of Neurospora crassa, the smaller subunit of MPP from Saccharomyces cerevisiae, and the core I protein of bovine ubiquinol:cytochrome c reductase. Lower homology is found with other members of a recently proposed class of endoproteases, which includes human insulinase and protease III from Escherichia coli. PMID- 8506386 TI - Breaching the conformational integrity of the catalytic triad of the serine protease plasmin: localized disruption of a side chain of His-603 strongly inhibits the amidolytic activity of human plasmin. AB - Site-directed mutagenesis has been used to construct a cDNA that encodes a recombinant variant human plasminogen (hPg) containing a Pro-611-->Ile mutation (MrhPg). The mutein was expressed in recombinant baculovirus-infected Spodoptera frugiperda cells (IPLB-SF-21AE), and purified. After activation of this zymogen to its corresponding form of the serine protease plasmin (MrhPm), this latter enzyme was essentially inactive toward an amide plasmin substrate, most likely from alteration of the spatial relationships of the active-site His-603 to its partners of the catalytic triad, Asp-646 and Ser-741. Partial amidolytic activity of MrhPm was restored as a consequence of imidazole addition to the assay medium, due to an increase in the catalytic constant kcat of the enzyme. The serine protease inhibitor, diisopropylphosphofluoridate, when preincubated with MrhPm, did not inhibit restoration of its amidolytic activity with imidazole, whereas diisopropylphosphofluoridate did inhibit the amidolytic activity of MrhPm in the presence of imidazole. This result implies that His-603 directly influences the nucleophilic character of Ser-741. When imidazole as pretreated with alpha-N tosyl-L-lysine chloromethyl ketone, the ability of this imidazole solution to restore amidolytic activity to MrhPm was eliminated, suggesting that N alpha-(p tosyl)lysine chloromethyl ketone directs into the binding pocket a derivatized form of imidazole, which is ineffective as an His-603 substitute. These results indicate that the conformational reorientation of His-603 results in a malfunctional catalytic triad in the serine protease MrhPm, thus leading to an inactive enzyme despite the presence of all three essential amino acids of the catalytic triad. Addition of extramolecular imidazole restores a portion of the amidolytic activity of this mutant enzyme. These data also argue for an enzyme mechanism in which the active-center His-603 residue directly influences the nucleophilicity of the active-site Ser 741 residue. PMID- 8506387 TI - Structure of a thymine-thymine adduct formed by menadione photosensitization. AB - The structure of one of the dithymine adducts formed by near-UV photosensitization of aqueous oxygenated thymine in the presence of 2-methyl-1,4 naphthoquinone is reported. The compound, 6' beta-hydroxy-5' beta-1-[5 methylpyrimidinyl-2,4-dione]-5'- 6'-dihydrothymine, has one thymine ring (ring I) linked through the 1-nitrogen atom to the C5' atom of a second thymine, which has been hydroxylated at C6' (ring II). Crystals are monoclinic, space group I2/c, and the structure was refined to R(obs) = 0.036 for 2072 unique reflections with intensities I greater than 2.33 sigma(I). Ring I is planar, whereas ring II is not. Ring I and the OH group on ring II are cis to ring II. The planar ring I and the OH group are attached, respectively, in an equatorial and axial manner to ring II (which is in the sofa conformation). The planar rings I of close-lying pairs of molecules stack parallel to each other. The structure is held together by a hydrogen-bonding system consisting of the water molecules, the NH groups, two of the C = O groups and the OH group. The chemical formula and relative configurations at C5' and C6' are established by this analysis. PMID- 8506388 TI - Uptake and bioconversion of alpha-tocopheryl acetate to alpha-tocopherol in skin of hairless mice. AB - The photoprotective effect of topically applied alpha-tocopheryl acetate (vitamin E acetate), a stable derivative of alpha-tocopherol (vitamin E), and its possible bioconversion to the active antioxidant species (alpha-tocopherol) was examined in skin tissue of female hairless mice (HRS/J) exposed to UV-B irradiation. Our results indicate that topically applied alpha-tocopheryl acetate is absorbed into and retained by skin tissue. Furthermore, skin tissue from UV-B-irradiated animals that received daily topical alpha-tocopheryl acetate treatments contained significantly higher levels (P < 0.001) of alpha-tocopheryl acetate than non-UV-B irradiated mice that received identical daily topical alpha-tocopheryl acetate treatments. Finally, free alpha-tocopherol levels in skin also were significantly increased (P < 0.001) by topical applications of alpha-tocopheryl acetate and skin levels of free alpha-tocopherol were significantly greater (P < 0.001) in UV B-irradiated animals that received daily topical alpha-tocopheryl acetate treatments than in non-UV-B-irradiated animals. These results suggest that UV-B irradiation enhances both the absorption of alpha-tocopheryl acetate and its bioconversion to free alpha-tocopherol. PMID- 8506389 TI - Characterization of the spectroscopic properties of a tetrahydrochrysene system containing a rigidified hydroxynitrostilbene chromophore: an inherently fluorescent ligand designed for the estrogen receptor. AB - A tetrahydrochrysene system that embodies a hydroxy- and nitro-substituted stilbene chromophore held rigidly near planarity by the tetracyclic nature of the compound was prepared as a fluorescent ligand for the estrogen receptor. It shows strong solvent-dependent fluorescence at long wavelengths. The solvent polarity dependence suggests that the fluorescence arises from an excited state with much n pi * character in cyclohexane; stronger emission comes from an intramolecular charge transfer state that has lower energy in more polar solvents, and finally progressive quenching of the charge transfer state occurs in solvents of higher polarity. The quenching effect is particularly evident in protic solvents. In water, however, the compound shows fluorescence of unusually high energy for an intramolecular charge transfer state, which suggests that photochemistry may be occurring. In solutions of gamma-cyclodextrin, emission from the nitrotetrahydrochrysene is red shifted and intensified relative to water. Photobleaching occurs in H2O but not in ethanol or gamma-cyclodextrin solution. The change in dipole moment between the ground and excited states for the nitrochrysene is 12.9 D, similar to our previous measurements for related nitrostilbenes. The compound displays red-shifted emission in triethylamine, perhaps due to an excited state hydrogen-bonded complex. The absorption and emission properties of the corresponding nitrophenolate were also studied. The nitrophenolate exhibits reverse solvatochromism in its absorption spectra. In conclusion, the high sensitivity of the emission energy and quantum yield of the title compound make it of potential utility as a fluorescent probe. PMID- 8506390 TI - Photocytotoxicity of water-soluble metalloporphyrin derivatives. AB - A new water-soluble porphyrin derivative, 2,4-bis(1-decyloxyethyl) deuteroporphyrinyl-6,7-bisaspart ic acid (C10-DP), and its metal complexes (Ga, I(n), Zn, Mn, Cu, Ni and Fe) were examined for their physicochemical properties (absorption, fluorescence, triplet lifetime and partition coefficient) and photocytotoxicity on HeLa cells. The five derivatives with longer (> 1 ms) triplet lifetimes (free base, Zn, Ga, I(n) and Sn complexes) exhibited remarkable photocytotoxicity, and the other derivatives (Mn, Cu, Ni and Fe), which had or were deduced to have fairly short (< 0.01 ms) triplet lifetimes, manifested no photocytotoxicity, indicating that the triplet lifetime of these derivatives played a significant role in their photocytotoxicity. Cellular fluorescence due to C10-DP and its gallium complex was observed mainly on the plasma membrane at the concentrations showing significant photocytotoxicity with low (< 32.6%) cytotoxicity in the dark (2-10 microM). PMID- 8506391 TI - Biological activities of phthalocyanines. XIII. The effects of human serum components on the in vitro uptake and photodynamic activity of zinc phthalocyanine. AB - The effect of human serum components on the photodynamic activity of zinc phthalocyanine (ZnPc) toward Chinese hamster fibroblasts (line V-79) was studied. Photodynamic activities were correlated with cellular uptake of radiolabeled [65Zn]ZnPc, which allowed corrections to be made for the amount of sensitizer present in the cells at the time of irradiation and to express photodynamic efficiencies on a cellular dye concentration basis. All serum components, with the exception of high-density lipoproteins, inhibit uptake of ZnPc by V-79 cells, when compared to incubation of ZnPc with the same cells in serum-free medium. High-density lipoproteins increased ZnPc uptake by 23%, but the photodynamic efficiency corrected for the cellular ZnPc concentration was unaffected. Very low density lipoprotein and globulins decreased ZnPc cell uptake but likewise did not affect the cellular photodynamic efficiency of the dye. In contrast low-density lipoprotein and albumin, while inhibiting ZnPc cell uptake, increased the cellular photodynamic efficiency of ZnPc, suggesting that these proteins facilitate localization of the dye at cellular targets sensitive to photodynamic damage and vital to cell survival. We conclude from these results that association of ZnPc with serum components can have important, and widely differing, effects on both degree of uptake and cellular distribution of the photosensitizer. PMID- 8506392 TI - Modified polyvinyl alcohol-benzoporphyrin derivative conjugates as phototoxic agents. AB - Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10,000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated 3H-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, especially in vivo. In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, the conjugate (1:25) reached slightly higher levels in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506393 TI - Relaxation of supercoiled DNA by aminomethyl trimethylpsoralen and UV photons: action spectrum. AB - An action spectrum for the relaxation of supercoiled plasmid DNA (induction of the first single-strand break) by photoactivated 4'-aminomethyl-4,5',8 trimethylpsoralen (AMT) has been determined using monochromatic UV photons from 254 to 405 nm. The spectrum of AMT-induced plasmid DNA relaxation fits closely with the absorbance spectrum of AMT in the spectral region between 313 nm and 405 nm but deviates at wavelengths shorter than 313 nm. This assay also reveals that the psoralen photosensitization reaction with DNA also produces piperidine-labile sites. Addition of mannitol and azide partially quenches the supercoil relaxation reaction, evidence for a role of Type II photosensitization pathway. PMID- 8506394 TI - Differential expression of pyrimidine dimer-binding proteins in normal and UV light-treated vertebrate cells. AB - The expression of UV damage-specific DNA-binding proteins was examined in various phylogenetically distant species with differing DNA repair phenotypes. Two distinct constitutive DNA-binding activities, one specific for cyclobutane pyrimidine dimers and the other for non-cyclobutane dimer photoproducts, were detected. The expression of these binding activities was found to be variable throughout the animal kingdom: cold-blooded vertebrates show a constitutive cyclobutane dimer-binding activity exclusively, and primates reveal only non cyclobutane binding activity. In contrast, birds and marsupials appear to express both types of binding activities. The kinetics of expression (rather than the constitutive presence) of these UV damage-specific DNA-binding activities after UV treatment correlate with the cell's capacity for DNA repair. In addition, cyclobutane pyrimidine dimer-binding activities could be detected only in cells with established photoreactivating activity. PMID- 8506395 TI - Early cell kinetic effects of a single dose of narrow-banded ultraviolet B irradiation on the rat corneal epithelium. AB - The right eyes of 40 rats were exposed to a single erythemogenic dose of ultraviolet B irradiation (UVB) at 297 nm. The irradiation was directed perpendicular to the center of the cornea. The left eyes served as controls. The animals were randomly assigned into 10 groups. The labeling index (LI) after pulse labeling with tritiated thymidine and the mitotic rate (MR) after Colcemid administration were registered in the corneal epithelium at predetermined intervals up to 96 h after the irradiation. A mathematical method was used to correlate corresponding corneal areas from the different animals. In the central cornea the LI was considerably reduced up to 36 h after the irradiation. The LI increased toward the peripheral cornea and reached normal values at the limbal area. The MR was also reduced up to 36 h. However, this reduction was over the entire epithelium. The block in cell proliferation was followed by increased proliferation. PMID- 8506396 TI - In vitro granuloma formation by spleen cells treated with psoralen plus long-wave ultraviolet radiation. AB - In vitro granulomas are induced by culturing murine spleen cells with artificial microparticles, dextran beads. In the presence of 0.5 microgram/mL 8 methoxypsoralen, UVA radiation (0.2-2.0 J/cm2) suppressed granuloma formation in a UVA dose-dependent manner. The doses of PUVA did not affect the cell viability as assessed by trypan blue exclusion. The time course of granuloma formation in 0.5 J/cm2 PUVA-treated cells was similar to that of normal spleen cells, with a maximum granuloma index at day 3 of culture, although a 49-63% suppression of granuloma formation was observed. PUVA-treated, nonadherent cells produced the same granuloma index when cultured with normal adherent cells. In contrast, a smaller granuloma index was observed in PUVA-treated adherent cells even when they were cultured with normal nonadherent cells. These data suggest that PUVA alters macrophages, resulting in the suppression of granuloma formation in vitro. PMID- 8506397 TI - In vitro and in vivo uptake of benzoporphyrin derivative into human and miniswine atherosclerotic plaque. AB - Benzoporphyrin derivative (BPD) has been demonstrated to be a new potent photosensitizer for photodynamic therapy (PDT). Although most of the work on BPD has been focused on its potential applications for cancer treatment, BPD may have potential clinical uses in the treatment of atherosclerosis. The purpose of this study was to determine in vitro and in vivo uptake of BPD into atherosclerotic plaque. Samples of atherosclerotic human femoral and popliteal arteries were incubated with BPD-monoacid, ring A (BPD-MA) for 1 h in the following concentrations: 1, 5, 10, 20, 30 and 40 micrograms/mL. Fluorescence from all samples was determined by chemical extraction with a spectrofluorometer. The tissue concentration for human arteries was 0.37 +/- 0.03, 2.78 +/- 1.5, 3.6 +/- 1.91, 7.15 +/- 2.36, 8.06 +/- 3.09 and 14.6 +/- 4.81 micrograms/g, respectively. In addition, three miniswine were rendered atherosclerotic and given BPD 2.0 mg/kg intravenously. The concentration of BPD-MA in miniswine aorta was 93-190 ng/g and the plaque/normal ratio was 1.7-3.5. For miniswine iliac arteries, the [BPD-MA] was 60-178 ng/g and the plaque/normal ratio was 1.1-3.3. Normal miniswine carotid artery contained 54 ng/g. This study showed that BPD-MA was taken up in atherosclerotic vessels both in vitro and in vivo and may have potential for PDT of atherosclerosis. PMID- 8506398 TI - Copper benzochlorin, a novel photosensitizer for photodynamic therapy: effects on a transplantable urothelial tumor. AB - An iminium salt of octaethylbenzochlorin with copper in the aromatic ring, CDS1, was tested for its tumoricidal effects on the AY-27 N-[4-(5-nitro-2-furyl)-2 thiazolyl] formamide tumor line. CDS1 was found to be an effective photosensitizer in vivo when used in combination with either a xenon arc lamp or a pulsed alexandrite laser. Hemodynamically, CDS1 and light caused a rapid decrease in tumor blood flow. Skin photosensitization was found to be minimal when drug-injected mice were illuminated in a solar simulator. PMID- 8506399 TI - Photosensory transduction in ciliates. I. An analysis of light-induced electrical and motile responses in Stentor coeruleus. AB - Light-induced membrane potential changes and motile responses have been studied in Stentor cells with intracellular microelectrodes and video microscopy, respectively. Intracellular microelectrode recordings showed that step-up increase in light intensity induced an electrical membrane response which consisted of an initial membrane depolarization (photoreceptor potential) followed by an action potential and maintaining phase of depolarization (afterdepolarization). The amplitude of the receptor potential is dependent on the intensity of light stimulus and the action potential appears with a lag period (latency) after the onset of light stimulus. The extent of the membrane afterdepolarization is dependent on the intensity and duration of stimulus used. A close time correlation has been established between the latency for the action potential and the onset of ciliary reversal (stop response). A time correlation was also observed between the duration of the membrane afterdepolarization and the duration of backward swimming. The action spectrum for the photoreceptor potential amplitude of Stentor resembled the action spectra for the latency of ciliary reversal and the photoresponsiveness, indicating that the photomovement response and membrane potential changes are coupled through the same photosensor system. A hypothesis on the photosensory transduction chain in Stentor is discussed according to which the photoreceptors and the ciliary apparatus is mediated by the membrane potential changes. PMID- 8506400 TI - Construction and characterization of hybrid luciferases coded by lux genes from Xenorhabdus luminescens and Vibrio fischeri. AB - Molecular cloning techniques were employed to obtain hybrid luciferases with their alpha and beta subunits encoded by luxA and luxB genes, respectively, from Xenorhabdus luminescens strain HW or Vibrio fischeri. Although the two wild-type luminous bacteria are phylogenetically diverged, the hybrid luciferase Xf comprising an alpha from X. luminescens HW and a beta from V. fischeri and the hybrid luciferase VI comprising an alpha from V. fischeri and a beta from X. luminescens HW were both functional in bioluminescence. Their general kinetic properties were close to the wild-type enzymes from which the alpha subunit was derived. The X. luminescens HW enzyme is distinct in having a high optimal temperature for in vitro bioluminescence, a high thermal stability and a sensitivity to aldehyde substrate inhibition. Comparisons of the Xf and VI hybrid luciferases with the two wild-type enzymes indicated that these unusual properties of the X. luminescens HW luciferase originated primarily from the alpha subunit. PMID- 8506401 TI - Alteration of dynamic quaternary structure and calcium-binding ability of beta crystallin by light. AB - beta-crystallin, one of the three main constituent proteins of the eye lens, exists as an equilibrium population of oligomeric (beta H), trimeric (beta L1) and dimeric (beta L2) species. This equilibrium is dependent on various factors such as the protein concentration, ionic strength and pH of the medium. We have studied the effect of ultraviolet B radiation on the aggregational patterns of beta-crystallin, using size-exclusion chromatography. Irradiation of a solution of beta H-crystallin at 295 nm for about 30 min causes the deaggregation of the hexameric population into dimers. Irradiation for a longer time, however, produces cross-linked high molecular weight products. Irradiation of a beta L2 solution for 30 min does not perturb the elution profile, while irradiation for a longer time increases the content of beta L1 (trimeric) crystallin. Irradiation also causes a decrease in the calcium-binding affinity of the beta-crystallins. PMID- 8506402 TI - Visualization of ultraviolet light-induced thymine dimers in DNA by immunoelectron microscopy. AB - To see the damage of DNA due to ultraviolet-B more distinctly, immunoelectron microscopic studies using a monoclonal antibody against cyclobutane-type thymine dimers were performed. As a result, we could detect the existence of thymine dimers on human genomic DNA and pUC18 plasmid DNA visually. This technique can be useful to locate the photoproducts formed on DNA. PMID- 8506403 TI - [The surgical treatment of epilepsy]. AB - Twenty percent of the approximately 800,000 epileptic patients in Germany cannot be treated adequately by pharmacotherapy alone. According to conservative estimates, epilepsy surgery could be of fundamental therapeutic benefit to at least 10-25% of these patients. A complex presurgical diagnostic program is the basis for any epilepsy surgery. Numerous methods are used to create a hypothesis about the location and size of the epileptogenic area. In addition, before surgery is performed, it must be established that no additional serious neurological or neuropsychological deficits will result from the planned resection. For this purpose, electrostimulation of the cortex and temporary anaesthesia of brain areas by amobarbital tests are performed. In intractable epilepsy originating in the temporal lobe about 60% of patients become seizure free after surgery. Another 15-20% benefit from surgery by a significant improvement in their seizure situation. Resections of the dominant temporal lobe result in further impairment of memory functions in about 20-30% of patients. PMID- 8506404 TI - [Magnetic resonance tomography in epilepsy]. AB - The most important causes of focal epilepsy are hippocampal sclerosis, circumscribed tumors, vascular malformations, trauma and perinatal damage. At the moment MRI is the best radiological imaging modality for localizing and characterizing a focus. In many cases, however, even MRI is negative. Especially in hippocampal sclerosis the diagnostic role of MRI is still not well established. Diagnostic criteria are side differences with hippocampal atrophy and circumscribed signal increase on T2-weighted images of the affected temporal lobe. Circumscribed lesions caused by tumors or vascular malformations are demonstrated very reliably by paracoronal T2-weighted sequences. Routine administration of the paramagnetic contrast material Gd-DTPA is not necessary. PMID- 8506406 TI - [Intracranial ECoG electrodes. Location determination using three-dimensional reconstruction of MR data of the brain as a component of the presurgical diagnosis of epilepsy]. AB - Subdural strip electrodes or intracerebral electrodes are required in order to precisely localize epileptic foci, which is mandatory for epilepsy surgery. The subdural electrodes are inserted via a borehole and thus precise positioning cannot be directly monitored. Therefore, the location of the electrodes in relation to the gyri and sulci has to be determined by imaging techniques. In this study, a three-dimensional magnetic resonance imaging (3D MRI) technique was used for visualization of intracranial EEG electrodes. A 3D gradient echo sequence with thin slices of 1 mm is required for the assessment of the gyral anatomy of the brain surface. Using a short repetition time of 30 ms good image quality within an acceptable acquisition time of about 15 min was possible. Post processing with 3D surface reconstruction was performed using a Sun workstation. Three-dimensional reconstruction allows a more precise delineation of the localization of the EEG electrodes and the simultaneous display of the adjacent brain structures. Misplacement of intracranial electrodes is readily detected. 3D MRI with 3D surface reconstruction proved superior to 2D imaging and CT for the assessment of EEG electrode localization. PMID- 8506405 TI - ["Spectroscopic imaging." A new MR technique in the diagnosis of epilepsy?]. AB - The technique of magnetic resonance spectroscopy fuses spectroscopic methods with the two-dimensional illustration of the metabolite concentrations by parallel acquisition of multiple single voxels from small tissue compartments. Therefore it is not necessary to define a voxel of interest before data acquisition. The interpretation of metabolite images is much easier than the analysis of single spectra, and metabolite concentrations on the right and left sides can be compared. The method has already proved reliable for brain tumors. The application of the procedure to patients suffering from epilepsy is described here in for the first time. Even in the temporal region, where most epileptogenic foci have their origin, one can obtain metabolite images of diagnostic quality without susceptibility artifacts. The epileptogenic focus is lateralized correctly, in accordance with electrophysiological and surgical evaluation, even in those cases where standard magnetic resonance imaging is normal. According to our preliminary findings the epileptogenic focus is characterized by a signal loss of N-acetyl-aspartate and creatine. PMID- 8506407 TI - [Neuroradiologic methods and findings prior to the surgical treatment of epilepsy in children]. AB - Epilepsy in childhood is often caused by morphological abnormalities and is frequently pharmacoresistant. Therefore it represents a challenge to the neuroradiologist because early and accurate diagnosis of abnormal morphology is the basis for planning surgical intervention with a high chance of controlling seizures and a low risk of complications. Both morphological (radiography, CT, MRI and angiography) and functional examinations [intracarotid amobarbital test (IAT)] are essential parts of the presurgical evaluation. In most cases MRI has proved to be most sensitive in detecting lesions except for some calcifications. Routine protocols for brain examinations are not sufficient, missing about 22% of lesions. Therefore a refined MRI and CT protocol is proposed. Even in very young children IAT can be performed at very low risk; these tests contribute highly valuable information about actual hemispheric dominance and other functions in more than 80% of procedures that is indispensable if postoperative neurological and neuropsychological deficits are to be avoided. PMID- 8506408 TI - [Single-photon, emission-computed tomography (SPECT) in the diagnosis of epilepsy]. AB - Regional cerebral blood flow can be measured using single photon emission computed tomography (SPECT). Hexamethyl propyleneamine oxime (HMPAO) is commercially available as a 99mTc-labeled tracer and has the advantage of fixing a blood flow pattern during its first passage through the capillaries. This can be used, for example, to evaluate a short-term ictal phase. With dedicated SPECT systems a spatial resolution of 5-8 mm can be achieved. Measurement using 133Xe allows absolute quantification of blood flow values, but the spatial resolution is lower. In about 50-70% of patients suffering from temporal lobe epilepsy a decreased blood flow in the focus can be visualized in the interictal phase. Ictally, focal hyperperfusion can be observed in most cases. The sensitivity and specificity of SPECT in the ictal phase are superior compared with interictal study. During the postictal phase a hyperperfusion of the anterior and mesial parts of the affected temporal lobe with simultaneous lateral hypoperfusion can often be demonstrated. At present, receptor SPECT has not yet reached clinical significance in the diagnosis of epilepsy. PMID- 8506409 TI - [The intracarotid amobarbital test. Neuroradiologic and neuropsychologic aspects]. AB - In presurgical evaluation of epilepsy, unilateral cerebral inactivation by means of intracarotid injection of amobarbital is used for the determination of cerebral dominance for language and memory functions. This intracarotid amobarbital test (IAT) is intended to yield prognoses concerning postsurgical neuropsychological and neurological deficits. In the present review, neuroradiological and neuropsychological aspects of the procedure are discussed. Each IAT is preceded by a cerebral angiography to exclude or detect vascular anomalies that might be relevant to the interpretation of neuropsychological test data. The main methodological problems of the IAT are interference of various cognitive deficits and monitoring of the course of amobarbital action. Alternative procedures of determination of hemispheric asymmetries--positron emission tomography, electrical stimulation mapping, and noninvasive methods like tachistoscopy--mainly yield data complementary to the results of the IAT and hence are not taken as substitutes of that technique. PMID- 8506410 TI - [The selective amobarbital test in epileptology]. AB - Epileptic foci in the frontal or parieto-occipital cortex often cause epileptiform EEG changes in both hemispheres. Therefore, delineation of the primary epileptogenic area, which is necessary for epilepsy surgery, is not possible by electrophysiological methods. A temporary inactivation of the epileptogenic area by a selective injection of the short-acting barbiturate amobarbital (selective amobarbital test, SAT) can prove the relation between generalized EEG changes and a circumscribed epileptogenic area. The SAT may also be used for evaluation of the risk for additional functional deficits after epilepsy surgery in certain brain areas. During temporary inactivation of the brain area to be resected, the function of the motor system, speech and memory can be tested. PMID- 8506411 TI - [Paraesophageal herniation of the greater omentum. Imaging by CT and MRT]. AB - A rare case of paraoesophageal omental herniation is presented and the CT and rapid-scan MRI findings demonstrated. The diagnosis was confirmed by laparatomy. PMID- 8506412 TI - [Bilateral hilar and mediastinal lymphoma with pulmonary infiltration]. PMID- 8506413 TI - Pathological evaluation of the regional lymph nodes in malignant melanoma. AB - The clinical implications of lymph node metastasis in patients with malignant melanoma remain serious. Five-year survival rate for clinical stage II disease is between 36% and 50% compared with more than a 80% 5-year survival rate for stage I melanoma. The purpose of this article is to review the known clinical and pathological risk factors for the development of lymph node metastasis in melanoma, to consider the prognostic significance of metastasis once it has occurred, and to discuss the histopathology and differential diagnosis of metastatic melanoma in lymph nodes. Our experience with selective lymphadenectomy for the detection of micrometastases is also presented. PMID- 8506414 TI - The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi. AB - Intermediate lesions of melanocytic tumor progression are potential precursors, simulants, and risk markers of melanoma. The clinical, public health, and biologic significance of intermediate lesions warrants their continued recognition and study, although improved schemata for their clinical and histological coding are needed. Blurred boundaries are inherently problematic to the categorization of lesions occurring along a stepwise pathway of increasing clinical and histological atypia. Nevertheless, the concepts of melanocytic dysplasia and of radial growth phase (in situ and microinvasive) melanoma are important to the classification of intermediate lesions of melanocytic tumor progression. Conceptually, these lesions are clearly separable from early and late lesions and from one another, and there is evidence that criteria distinguishing them can be reproducibly applied. Analysis of these intermediate lesions suggests that they represent responses to events (perhaps mutational) induced by ultraviolet light in constitutionally hypersensitive individuals, supporting epidemiological data that implicate sunlight as an etiologic agent for most melanomas. The continuing rigorous application of the methodologies of epidemiology and basic science to the study of these lesional steps will likely lead to the recognition of biologic markers to better distinguish benign from malignant melanocytic lesions. PMID- 8506415 TI - Nevi, other than dysplastic and Spitz nevi. AB - Cutaneous nevi are common lesions that develop by proliferation of melanocyte derived cells. The majority develop as junction nevi from melanocytes at the epidermo-dermal junction. Cells from this proliferation pass into the underlying dermis forming compound nevi. Later junctional melanocytic activity ceases, leaving an intradermal nevus. A minority of nevi, mainly blue nevi, arise from intradermal melanocytes. Histological variants of melanocytic nevi exist and can be the source of difficult diagnostic problems. Nevi are important as clinical and histological simulators of cutaneous melanoma, as precursor lesions for melanoma (although the actual chance of malignant transformation of an individual nevus is low) and as cosmetic problems (mainly large congenital nevi). Cutaneous nevi are to be separated clinically and histologically from melanomas that are comprised of nevocyte-like cells (minimal deviation melanoma). PMID- 8506416 TI - The histology and differential diagnosis of Spitz nevus. AB - We attempted to identify features by which Spitz nevi (SN) and melanomas that resemble SN may be distinguished, by examining the light microscopic features of 43 SN, using a multifactorial protocol. The data confirm that SN evolve in a manner similar to melanocytic nevi, with well-defined junctional, compound, and intradermal phases. Because of their growth kinetics most SN are excised at the compound stage, the most readily identifiable stage of evolution. However, almost 20% of SN are removed before or after the compound stage and at these stages they are recognized less readily. There are common characteristics of the histological features of the epidermis, junctional and dermal melanocytes, and stromal components at the different stages of SN evolution, but each stage additionally has unique characteristics. Each stage of SN has to be separated from different benign and malignant melanocytic lesions and criteria by which these separations may be made are discussed. PMID- 8506417 TI - The histopathology of cutaneous malignant melanoma. AB - The vast majority of cutaneous malignant melanomas (CMM) develop from a proliferation of intraepidermal melanocytes that may progress through radial (including in situ and microinvasive stages) and vertical growth phases (VGP). The currently accepted classification of melanoma is based on the presence (eg, superficial spreading, lentigo maligna, or acral lentiginous melanoma) or absence of a radial growth phase (nodular melanoma). Although not standardized, melanoma may also be classified as to the nature of the VGP, eg, as expansile nodules composed of epithelioid cells, spindle cells, or smaller nevus-like cells supervening on one of the radial growth components previously mentioned, or developing de novo. Less common variants of the VGP include desmoplastic and neurotropic melanomas (often arising with lentiginous melanomas), and the controversial (and perhaps mainly conceptual) entity, minimal deviation melanoma. Other unusual or rare forms of melanoma are malignant blue nevus, balloon cell melanoma, and clear cell sarcoma. An extensive discussion of the differential diagnosis of the various types of melanoma is provided. PMID- 8506418 TI - Immunohistochemistry in the evaluation of melanocytic tumors. AB - A review is given on the classification of melanoma-associated antigens and their relevance as tumor markers in tissue sections and cell preparation. Applications of immunohistochemistry in the diagnosis and prognosis of melanocytic tumors are discussed. PMID- 8506419 TI - Electron microscopy in the evaluation of melanocytic tumors. AB - Melanoma is the "syphilis of malignant tumors", said one of my favorite mentors (Dr Jerome Wollman, Wadsworth VA Hospital, Los Angeles, California). What syphilis is to clinicians, melanoma is to surgical pathologists. By light microscopy, melanoma, especially in its metastatic form, can exhibit any imaginable pattern, can be amelanotic, and the immunostaining can be negative or equivocal. The present review deals with the features of both classic and aberrant forms of melanosomes. In addition to melanosome morphology, spectrum of ultrastructural features of usual and unusual histological variants of melanoma are described and illustrated. Finally, the role of immunoelectron microscopy is discussed briefly. PMID- 8506420 TI - Impact of a parent's cancer on adult children: role and relationship issues. AB - The diagnosis and initial treatment of a parent for cancer is a highly stressful process that generates a variety of concerns for adult children. This study describes the initial effect of a parent's cancer on adult children. Adult children's concerns about role and relationship issues emerged as major themes in the content analysis of their interviews. PMID- 8506421 TI - Sibling bereavement: research-based guidelines for nurses. AB - Despite the marked improvement in the treatment of childhood cancer in recent decades, there are children who die, leaving behind a legacy of grief for all who knew them, including their siblings. Nurses can play a significant role in facilitating healthy grieving for these surviving children. The results of several studies pertaining to sibling bereavement after the death of a child from cancer provide guidelines for clinicians. PMID- 8506422 TI - Needs of family caregivers of persons with cancer: a review. AB - The focus of cancer patient care has moved from the hospital to the home as a result of shortened acute-care stays and subsequent early discharges. Thus, family members and friends frequently must assume the caregiving role. Research has provided information regarding who in the family assumes the responsibility for care of the cancer patient, the needs of these family caregivers, community resources available, and service gaps within the present health care system. PMID- 8506423 TI - Survival work: the experience of the patient and the spouse involved in experimental treatment for cancer. AB - The unpredictable course of cancer and its treatment and the ability to adjust to these uncertainties may influence the psychological stress experienced by the patient and family as well as their ability to engage in coping activities. This study describes the experiences of patients--and their spouses--involved in experimental therapy for advanced cancer, including their decision to enter a clinical trial and the processes that contributed to the patients' continuation of treatment. PMID- 8506424 TI - Psychosocial transitions and the family's work in adjusting to cancer. AB - The family, not just the patient, experiences and attempts to understand the meaning of cancer. The family's adjustment to cancer involves moving through psychosocial transitions in ways that facilitate the meaning of the experience; that maintain the family's ongoing functions; that respond to the illness-related demands; that maintain the self-esteem of the family members; and that foster new arrangements and relationships in the family that are responsive to the contingencies of the illness. PMID- 8506425 TI - Cancer and the family: strategies to assist spouses. AB - Research that has been conducted with spouses of cancer patients documents the nature of their stress, the duration of their stress, and the concerns that they confront over the course of the illness. A variety of intervention strategies have been used to assist spouses in dealing with the stressful effects of cancer. Two major categories of intervention strategies are providing information and offering support. PMID- 8506426 TI - The impact of breast cancer on the partner 18 months after diagnosis. AB - Little attention has been given to the partner's long-term experience after his wife's diagnosis of breast cancer. The results of this current study highlight the opportunity for nurses to make a difference in the distress levels of patients' partners after the diagnosis of breast cancer. Long-term negative effects can be seen in partners' fears about disease recurrence and marital problems related to breast cancer. PMID- 8506427 TI - Issues, problems, and challenges for families coping with breast cancer. AB - There is a scarcity of research that examines the adaptation of the family to breast cancer from the family's perspective. This study analyzed 12 families from the time of diagnosis to 12 months later. Issues, problems, and challenges that partnered families faced during the initial year were identified through five interview points. Frequency of the problems identified and the challenges encountered shifted over time. PMID- 8506428 TI - [What is your diagnosis? Tinea profunda]. PMID- 8506429 TI - [Rheumatological manifestations and HIV infection]. AB - The spectrum of clinical manifestations in HIV infection has expanded considerably over the last few years. Several rheumatological syndromes have been associated with HIV infection such as Reiter's syndrome and other reactive arthritides, undifferentiated spondylarthropathy, but also HLA-B27-negative oligoarthritis, myopathy, Sjogren-like syndrome and vasculitis. Systemic lupus erythematosus and rheumatoid arthritis appear to be modified by the HIV infection. Further insight into interactions between HIV infection and these rheumatological syndromes will enlarge our epidemiological and pathogenetical understanding of the complex mechanisms involved. Awareness of such interactions is critical with respect to factors regarding both prognostic and therapeutic implications in the management of HIV infected patients. PMID- 8506430 TI - [Arthritis in adolescence]. AB - Joint problems in adolescence are often monoarticular. In the acute form the differentiation between trauma and infection is of utmost importance, whereas in chronic joint diseases the differentiation will be mainly between mechanical disorders and true rheumatic diseases. In pauci- or polyarticular arthritis of short duration viral infections have to be considered, since true rheumatic diseases tend to run a more chronic course. In girls true sero-positive juvenile rheumatoid arthritis typically appears in this age group. In adolescent boys seronegative Spondylarthropathies involving the lower extremities and not uncommonly with enthesopathies may occur. The typical involvement of the sacro iliac-joint usually starts after the age of 18 years. Bacterial arthritides are predominantly monoarticular and are caused in more than 50% by staphylococci. PMID- 8506431 TI - [Laboratory diagnosis of monarthritis: how much, what for, when?]. AB - Analysis of the synovial fluid is the major investigation of monoarthritis. Appearance, viscosity (low if inflamed), cell number and differential, presence of crystals or organisms are all relevant. If septic arthritis is suspected, culture of other sites such as blood, urine, sputum etc. is essential, and may alone yield the organism. If mycobacterium is possible, synovial membrane staining and culture is usually necessary. Gonococcal may be lost in culture if the specimen is not immediately processed. Partially treated sepsis may produce sterile culture, and early work suggests that P.C.R. may diagnose these cases. Other investigations such as erythrocyte sedimentation rate, C-reactive protein indicate inflammatory activity, though they are not specific. Antibodies such as antinuclear antibodies, rheumatoid factors lead towards an "autoimmune" disease diagnosis, that do not alone measure activity. Specific antibodies to virus e.g. parvovirus may be diagnostic. The monoarthritis must be seen in the total patient context, where often clues e.g., asymptomatic uveitis (in juvenile chronic arthritis) and psoriasis may give the diagnosis. PMID- 8506432 TI - [Synovial biopsy: expectations, results and assessment]. AB - In arthropathies without clear diagnostic clinical, radiological and laboratory findings, a synovial biopsy should be performed. The histologic examination yields a diagnosis in 5 to 29% or is complementary to clinical, radiological and laboratory findings leading to the diagnosis in another 23 to 40%; the diagnosis of "chronic synovitis" results at best for the remaining cases. The histological features of the main types of arthritis and arthropathy are briefly discussed. PMID- 8506433 TI - [What is your diagnosis? Right lower lobe pulmonary sequestration]. PMID- 8506434 TI - [Efficacy and tolerance of terbutaline and budesonide administered via a pressurized aerosol inhaler or a Turbohaler in asthmatic patients]. AB - 35 asthmatic patients, aged from 23 to 73 years, participated in an open study aimed to compare the efficacy and tolerance of terbutaline and budesonide administered in similar amounts with a metered-dose inhaler fitted with a spacer (Nebuhaler) or by a powder inhaler (Turbuhaler). The patients used each device for seven weeks after a running-in phase of two weeks and gave at the end their preference for one or the other mode of administration. Among lung function values, the forced expiratory volume in the first second (FEV1) was significantly higher during the Turbuhaler period than during the period with metered-dose inhaler whereas the forced vital capacity, mid-expiratory flow rate and peak-flow morning and evening were not significantly different. The use of beta 2 bronchodilators and clinical scores were similar with a non-significant trend in favor of the Turbuhaler period. 25 patients on 35 expressed a preference for the Turbuhaler. The administration of terbutaline and budesonide by Turbuhaler is similarly or more efficient then the inhalation from a metered-dose inhaler with a Nebuhaler spacer and is preferred by a majority of patients. PMID- 8506435 TI - [Inhalation devices]. AB - Currently available devices allow the administration by inhalation of many active drugs directly into the bronchial tree, and with minimal side effects. The choice of the device depends first on the properties of the drug and the ability of the patient to use it correctly. Economical and ecological considerations as well as the current practice of the prescribing doctor play also a role. Whatever the system, the instruction and training of the user must be done carefully and controlled regularly. PMID- 8506436 TI - [Continuous home oxygen therapy in chronic obstructive bronchopneumopathy]. AB - Long-term oxygen therapy (LTOT) has a significant effect on the survival of patients with chronic obstructive bronchitis and/or emphysema (COPD). The rationale for this therapy is based on prevention of the increase in pulmonary arterial tension resulting from chronic hypoxia. There are several problems in the application of this treatment to individual patients, and they are reviewed in this paper. Indication for LTOT depends on precise criteria. Information to the patients and to the medical community is essential for the success of this therapy. PMID- 8506437 TI - [Assisted ventilation at home]. AB - In patients with chronic respiratory failure, in particular in those with accompanying wall-dependent restrictive syndrome (i.e. kyphoscoliosis, certain myopathies...) shortness of breath and sequelae of cor pulmonale usually limit quality of life distinctly. In particular repeated hospitalizations necessitated by remittent occurrence of severe respiratory decompensation, usually in the course of infections, reduce life quality and life expectancy. Thus, selected patients may benefit remarkably from a device for assisted ventilation at home as a technical measure with good results. The number of hospitalizations is markedly reduced, shortness of breath can even disappear completely, so that patients can regain social activity. The usually non-invasive technique (ventilation with nose mask) is applied at night, so that disturbance is low for the patient and his surroundings. It is however necessary, that his financial burden and technical maintenance and servicing of materials is granted by an organisation, who is also able to provide safety for the patient and his family on a long term. PMID- 8506438 TI - [Treatment of sleep-associated respiration disorders in clinical practice]. AB - The actual therapy of choice for the common obstructive sleep-apnea syndrome is the application of continuous positive airway pressure (CPAP) via a nose-mask. This ventilation by positive pressure is explained in some detail. Mechanical ventilation for treatment of nocturnal respiratory failure in outpatients of various etiologies is covered in the companion paper by J. C. Chevrolet. Treatment of sleep disorders due to other pulmonary diseases such as bronchial asthma and others require treatment of the underlying disorder. PMID- 8506439 TI - [Heart-lung transplantation, single lung and both lungs]. AB - Following the improvement in surgical techniques and immunosuppression regimens as well as a better selection of recipients, an increasing number of heart-lung, single lung and double lung transplantations have been performed within the last decade. In the early stages, most candidates had advanced pulmonary hypertension. More recently, patients with end-stage lung disease have been successfully transplanted. Providing the allografts remain free of complications, long-term survivors may benefit of well preserved pulmonary function. However, acute rejection, obliterative bronchiolitis and infections are still a major cause of morbidity and mortality. PMID- 8506440 TI - [Are home blood pressure measurements and 24-hour ambulatory recordings superior to office measurements? Comparison of 3 blood pressure recording methods in a study of cilazapril versus atenolol]. AB - Self-assessment of blood pressure and ambulatory blood pressure monitoring (ABPM) are being more widely used in the diagnosis and therapy of hypertension, in addition to office blood pressure measurement. The present multicenter double blind study compared cilazapril 2.5 to 5 mg (n = 26) to atenolol 50 to 100 mg (n = 27) over a period course of eight weeks. Office blood pressures in the morning before medication, ABPM over 24 h and self assessment of the blood pressure in the morning and evening were taken. The aim of the study was to find out if the results of ABPM and self assessment of blood pressure are similar when compared to office blood pressure measurement. After four weeks of therapy both cilazapril and atenolol achieved a significant and comparable reduction of blood pressure, which did not change significantly afterwards. Both medications showed a comparable blood pressure control over 24 h. with a once-a-day regimen. The comparison of the three techniques of blood pressure measurement demonstrates that ABPM results in significantly lower average daily values than office blood pressure measurement and that the self-assessed blood pressure values in most cases lie in-between. Although the diastolic ambulatory daily values were on the average 9 mmHg lower than the corresponding office values, it was not possible for an individual patient to accurately predict the ambulatory value obtained by to his office blood pressure value. Similar results were found for the values according to self assessment of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506441 TI - [Back pain]. AB - This 54 year old male patient complained of upper back pain for four months, which increased on physical exertion. An X-ray examination of the spine showed compression fractures of the anterior aspects of the thoracic vertebrae VI and XI as well as anterior aspects of the thoracic vertebrae VI and XI and signs of osteoporosis. Physical examination revealed signs of hypogonadism as well as eunuchoid disproportions of the skeleton. Serum tests gave evidence of a hypogonadotropic hypogonadism due to isolated LH-secretion deficiency (Pasqualini syndrome) with secondary osteoporosis. PMID- 8506442 TI - [A case from practice (268). Dilated cardiomyopathy in AIDS]. PMID- 8506443 TI - [Possibilities of catheter therapy in vascular stenosis, vascular abnormalities, tumors and hemorrhages. Synopsis of an interdisciplinary colloquium]. AB - Modern interventional catheter-technics allow amelioration of arterial blood flow by dilatation of narrowed or recanalization of closed coronary and peripheral arteries. Patients with chronic or unstable angina pectoris not responding to therapy can thus be treated successfully by percutaneous dilatation (PTCA). In peripheral occlusive disease balloon catheterization sometimes in combination with local fibrinolysis and thrombectomy may prevent amputation. On the other hand, cerebral malformations of arteries, aneurysms and tumors can be eliminated by artificial occlusion. Therapeutic embolization is also increasingly used in acute or recurrent haemorrhage in lungs, spleen and gastrointestinal tract. It may also be used as palliating therapy in malignancies. Medical indications and limitations of the various catheter techniques in cardiology, angiology, neurology and interventional radiology are discussed. PMID- 8506444 TI - [What is your diagnosis? Alcohol-induced hallucination]. PMID- 8506446 TI - [Pain assessment and documentation in patients with tumors: theory and reality]. AB - Each tumor patient with pain is not only entitled to a careful diagnostic workup and to effective treatment of his pain syndrome, but also to a clear and useful documentation of the course of his pain(s). This documentation ('pain evolution chart') should at least include the main location(s) of the treated pain and the varying pain intensity during the course of the day as well as at night. A respective pain documentation instrument, the St. Gallen Pain Evolution Chart (S PEC), was presented as a practical example, together with a brief review of the literature. The 'pain evolution chart' should be a regular part of the patient's hospital chart, as it forces the patient and his care-givers to cope more constructively with the present pain syndrome. The (well instructed) patient himself is responsible for an accurate and realistic pain documentation. Such longitudinal 'pain evolution charts' are not only useful for clinical oncology practice but also for clinical pain and analgesic research. PMID- 8506445 TI - [Current aspects in the pathophysiology of tumor-associated pain--consequences for clinical practice?]. AB - Peripheral and central mechanisms involved in generation, modulation and perception of pain are discussed. Lesions of peripheral nerves are a particular cause of pain, which has to be recognized as such, as it requires specific therapeutic measures. Emphasis is put on the role of ephaptic transmission. PMID- 8506447 TI - [Pain and fatigue in tumor patients]. AB - Diagnosis, assessment and treatment of pain are probably among the most significant achievements of modern medicine. Today patients with neoplastic diseases must be much less afraid of devastating pain than only a few years ago. According to the WHO 90% of the tumor-associated pain should be controlled, provided the available knowledge is effectively applied. Fatigue is increasingly recognized as a future major problem in these patients and it also is a sign of consuming disease processes. Subjectivity of both aforementioned symptoms requires also a subjective assessment i.e. measurements taken by the patient himself and acceptance of this self-assessment by those providing care. Fatigue, like pain is not only explained by biologic mechanisms but also understood as multidimensional concept including psychological aspects and social environment. Apart from pain-research, the recording of the course of fatigue-states, the definition of qualitative and quantitative aspects of fatigue and the development of therapeutic approaches to fatigue, will be objects of future research. The recognition of receptor-systems for pain evoke the hope for receptor-involvement in fatigue and the possibility for drug-receptor interactions. Even then these receptors will belong to individuals. PMID- 8506448 TI - [Pain in society and in medicine]. AB - Pain as a psychophysical experience and in particular its treatment have always been--and are particularly nowadays--an essential problem in medicine. Beyond that pain has a multitude of connections to human existence. The phenomenon of pain appears in almost all areas of art (painting, sculpture, music and poetry), philosophy and the religions. In the arts pain and its expression is often proof of the noblest esthetic-spiritual creativity; in medicine on the other hand it touches only the depth of human existence, then, when severe, chronic pain leads to disintegration of personality. From these propositions emerges that pain is not only sensed but is also a sentiment. Both belong together in an inseparable act of passive acceptance and active creative experience. Whereas the phenomenon of pain has earlier been seen in its alternative respective components such as physical or spiritual, it is in modern times, following the holistic perception of medicine, regarded as complementary. This complementary view is also the basis for the various forms of combined pain-treatment in use today. PMID- 8506449 TI - [Suffering and suicide in tumor patients]. AB - Epidemiological studies demonstrate that cancer patients are at increased risk for suicide. Vulnerability to suicide in cancer patients is influenced by a number of factors, including psychosocial and psychosomatic effects of advanced illness, pain, organic mental syndromes and pre-existing psychopathology. Ways of influencing these risk factors are discussed, together with their use in preventive care and management of suicidal cancer patients. PMID- 8506450 TI - Amphetamines and narcolepsy: use of the Stanford database. PMID- 8506451 TI - Amphetamine prescription. PMID- 8506452 TI - Sleep patterns in reading disabled children. AB - Sleep patterns in reading disabled (n = 24) and normal control (n = 15) 8-10-year old boys were compared to examine suggested relationships among sleep, maturational and cognitive processes. Sleep was recorded in the laboratory for four consecutive nights (two adaptation, two baseline) using standard polysomnography. Analyses revealed variations across nights for both groups reflecting adaptation to the sleep laboratory, but such effects were attenuated in reading disabled subjects. Group comparisons on baseline sleep measures (nights 3 and 4 collapsed) revealed that reading disabled children showed significantly more stage 4 sleep, less rapid eye movement (REM) sleep, a longer REM onset latency and, related to this, an extended initial non-REM (NREM) cycle. Chronic sleep deprivation and maturational delay are prominent among factors that could result in such variations in sleep architecture, and these factors, alone or in combination, could impair information processing and contribute to cognitive deficits noted in reading disabled children. PMID- 8506453 TI - Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. AB - We treated 24 patients with narcolepsy for 4 weeks with gammahydroxybutyrate (GHB), 60 mg/kg/night, in a randomized double-blind placebo-controlled cross-over trial. Both clinical and polysomnographic criteria were used to assess the results. Compared to placebo, GHB reduced the daily number of hypnagogic hallucinations (from 0.87 to 0.28; p = 0.008), daytime sleep attacks (from 2.27 to 1.40; p = 0.001) and the severity of subjective daytime sleepiness (from 1.57 to 1.24 on a 0-4 scale; p = 0.028). The number of daily cataplexy attacks was reduced from 1.26 at baseline to 0.56 after 4 weeks of GHB intake. This reduction, however, was not statistically significantly different from the difference between baseline and placebo. GHB stabilized nocturnal rapid eye movement (REM) sleep, i.e. it reduced the percentage of wakefulness during REM sleep (p = 0.007) and the number of awakenings out of REM sleep (p = 0.016), and tended to increase slow wave sleep (p = 0.053). Adverse events were few and mild. We conclude that GHB is an effective and well-tolerated treatment for narcolepsy. PMID- 8506454 TI - Sleep deprivation in the rat: XVII. Effect of aspirin on elevated body temperature. AB - Previous studies of total sleep deprivation (TSD) in the rat have shown an elevation of waking body temperature (Tb) early in the deprivation period. TSD rats defend this rise behaviorally by selecting warm ambient temperatures and autonomically by increasing heat production, thus indicating an elevation of thermoregulatory setpoint. Prostaglandins (PGs) can elevate setpoint and Tb. To investigate whether the TSD-induced rise in setpoint and Tb was mediated by PGs, aspirin, which blocks the synthesis of PGs, was administered 100 mg/kg s.q. to 11 TSD and 13 control (TSC) rats in baseline and deprivation. During baseline, aspirin produced a nonsignificant (0.16 degrees C) rise across all rats in waking Tb. For the sampled time period, waking Tb during deprivation day 3 was significantly elevated in TSD rats (0.64 degrees C, p < 0.01) but not in TSC rats (0.27 degrees C). Aspirin was administered on deprivation day 4. It produced a fall in waking Tb in TSD rats from its deprivation-induced elevation. The difference between the response to aspirin during baseline and during deprivation was significant (-0.25 degrees C, p < 0.05) for TSD rats but not TSC rats (-0.17 degrees C). Time awake after aspirin increased significantly (16.2%, p < 0.05) during baseline and declined nonsignificantly (1.1%) during deprivation. These data imply that at least part of the rise in Tb that is characteristic of TSD is mediated by PGs. To the extent that PGD2 promotes lower Tb and sleep in rats but PGE2 has opposite effects, the results are consistent with a shift from PGD2 predominance in baseline toward PGE2 predominance during TSD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506455 TI - Level of sleepiness and total sleep time following various time in bed conditions. AB - The effects of various time in bed (TIB) conditions on daytime sleepiness and total sleep time (during a 24-hour enforced bedtime) were investigated. Thirty two healthy male subjects participated in the study. Subjects were assigned to one of four groups to balance average screening multiple sleep latency tests (MSLT). Subjects were randomly assigned to spend 8, 6, 4 or 0 hours time in bed. They underwent the same TIB condition twice with at least 7 days between the two sessions. Following their assigned time in bed conditions, subjects were counterbalanced to have a standard MSLT and a 24-hour enforced bedtime protocol. To assess the effect of TIB on the MSLT, the sleep latencies were submitted to a four (TIB condition) by four (nap test) multivariate analysis of variance. The sleep latencies were shorter for those subjects in the 0-hours condition when compared to the other three conditions. Also, the sleep latencies of those subjects in the 4- and 6-hour conditions were comparable but different from those of subjects in the 8- and 0-hour TIB conditions. To assess the effect of TIB on the 24-hour enforced bedtime, the total sleep time during this period was submitted to a six (4-hour block) by four (TIB condition) multivariate analysis of variance. Subjects slept more following 0 hours TIB when compared to the other three conditions. There were no statistically significant differences between the 8-, 6- and 4-hour TIB conditions. Across conditions, subjects slept more during the first 4 hours when compared to blocks 2, 3, 4 and 5. Blocks 1 and 6 were comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506456 TI - A comparison between visual and computer assessment of sleep onset latency and their application in a pharmacological sleep study. AB - Sleep onset latency (SOL) is frequently defined as the time between lights-out and the first epoch of sleep stage 2. In practice, SOL can be quantified easily on the basis of visual examination. We have developed a computer algorithm allowing an automatic estimation of this parameter. The agreement between both strategies, visual and computer analysis, was tested using data from a pharmacological sleep study with 16 elderly insomniacs, which was aimed at comparing the effects of lormetazepam and zopiclone on polysomnography. A high correlation was found between the visual and the computer-based determination of SOL. Drug-related differences in SOL could be shown with both approaches. PMID- 8506457 TI - Automatic detection of K-complexes: validation in normals and dysthymic patients. AB - A model-based automatic K-complex (Kc) detector was applied to all-night single channel sleep electroencephalographic (EEG) recordings from normal and dysthymic patients. The performance of the detector was analyzed in the two groups, and the differences obtained were discussed. The results showed that the detection rate of Kc in the normal group was around 92% through all stages of non-rapid eye movement (NREM) sleep, but with high numbers of "false" positives in stage 4 NREM, which reached 57%. In the dysthymic patients "true" detection included 85% of the Kc, but the percentage of "false" positives dropped to 25% in stage 4 NREM. Most of the "false" detections in the normal group were due to sharp delta activity during slow wave sleep (SWS). The results in the patient group were expected, because sleep in dysthymics showed a reduction in SWS when compared to normals. The behavior and automatic artifact rejection mechanisms of the detector are briefly presented. The model-based Kc detector performed significantly better than other automatic detectors described in the literature; it was found to be a useful tool for routine sleep EEG studies. PMID- 8506458 TI - Physician education in sleep and sleep disorders: a national survey of U.S. medical schools. AB - A national survey was conducted of 126 accredited medical schools in the United States to evaluate physician education in sleep and sleep disorders and to identify potential obstacles to effective teaching in the area. Parallel survey instruments were designed to evaluate preclinical and clinical training in sleep. Instructors indicated the specific courses in which this material is taught, the format of teaching, methods of student evaluation, assigned readings and clinical experience and educational resources provided. A total of 545 responses were received, which represents an 82.6% overall response rate. Responses were obtained from all accredited medical schools, and the sample was about equally divided between preclinical and clinical course directors. Less than 2 hours of total teaching time is allocated to sleep and sleep disorders, on average, with 37 schools reporting no structured teaching time whatever in this area. Only 8% of medical students are trained in the use of sleep laboratory procedures, and 11% have participated in the clinical evaluation of sleep-disordered patients. Less than 5% of medical schools offer 4 or more hours of didactic teaching on sleep, most of which consists of 4th year elective experiences. More than two thirds of the survey respondents stated that current education is inadequate and that additional time should be devoted to this area. The major obstacles reported are the unavailability of qualified faculty, lack of curriculum time and the need for additional clinical and educational resources. Overall, it appears that physician education in sleep and sleep disorders is largely inadequate, despite increasing evidence of the role of sleep in patient health and well-being. PMID- 8506459 TI - Transient recurrent situational insomnia associated with cluster headache. AB - Headache syndromes are known to occur in association with sleep. Both the clinical and the polysomnographic abnormalities occurring in association with various headache syndromes have been described. We report the occurrence of transient recurrent situational insomnia that occurred in association with chronic cluster headaches and was reversible after the headache cluster subsided. This seems to represent a further degree of sleep disturbance in addition to the previously described insomnia and other abnormal polysomnographic features that may occur in direct association with the headache syndromes. PMID- 8506460 TI - Association between puberty and delayed phase preference. AB - Many teenagers go to bed and wake up significantly later than younger children, a developmental progression thought to reflect adolescent psychosocial processes. To determine whether biological processes may underlie a delay of phase preference in adolescents, 183 sixth-grade boys and 275 sixth-grade girls completed questionnaires for morningness/eveningness (M/E) and pubertal status. School environment and birth order were also evaluated. A significant relationship of pubertal status to M/E was found in girls, with a similar though nonsignificant trend in boys. No relationship between M/E and psychosocial factors was found. These data support involvement of a biological factor in the adolescent phase preference delay and indicate that our current understanding of adolescent sleep patterns may need revision. PMID- 8506461 TI - Infant-parent co-sleeping in an evolutionary perspective: implications for understanding infant sleep development and the sudden infant death syndrome. AB - Evidence suggests that infant-parent co-sleeping represents the species-wide pattern of sleep in which human infant physiology evolved. The hypothesis evaluated in this manuscript is that the co-sleeping environment may foster development of optimal sleep patterning in infants and confer other benefits, including reducing the risk of the sudden infant death syndrome (SIDS). These postulations by McKenna are considered from different perspectives by the coauthors. Using evolutionary, cross-species, crosscultural, physiological and behavioral data, our objective was to present a conceptual framework for assessing the developmental consequences of solitary sleeping and infant-parent co-sleeping. PMID- 8506462 TI - Sleep disorders. PMID- 8506464 TI - Bibliography of recent literature in sleep research. PMID- 8506463 TI - T-sleep: an improved method for scoring breathing-disordered sleep. PMID- 8506465 TI - [Radiologic pitfalls of mandibular fractures]. AB - Analysis of a large series of patients treated for mandibular fractures showed pitfalls in assessment of radiologic images in six cases. Factors predisposing to these radiologic pitfalls are discussed, multiple radiographic projections being suggested if discordance exists between radiologic and clinical findings, to obtain maximum data from a three dimensional picture of the mandible. PMID- 8506466 TI - [Chronic and neglected luxation of the temporomandibular joint]. AB - The authors propose their experience about 6 cases of chronic dislocation of the temporo-mandibular joint. They underline the part of edentulous status as a predisposing factor also that of the anatomopathological injuries of the dislocated joint. According to the literature, they insist about the importance of surgery to set the dislocation, that in association with a temporal aponevrosis flap and occlusal adjustment, accompanied by immediate postoperative rehabilitation. PMID- 8506467 TI - [Our experience using free vascularized bone flaps in mandibular reconstruction. The external brachial flap, the fibular flap, the para-scapular flap]. AB - New techniques developed over the last decade use vascularized bone flaps for maxillofacial reconstructive surgery. Indications for use of three recently described flaps (external brachial, fibular, parascapular) are discussed as a function of the regions to be reconstructed. Three clinical cases are presented, each patient having received one type of flap. PMID- 8506468 TI - [Maxillofacial prostheses on endosseous implants. Various modes of fixation]. AB - Both mechanical and magnetic types of fixation can be used with extra-oral implants, with the possibility of positioning maxillofacial prostheses by either mechanical, magnetic or mixed fixation, the latter by a combination of the two methods. These different modes of fixation allow precise positioning, avoid the use of adhesives, limit maintenance problems and, in addition, facilitate oncologic surveillance, providing a non-negligible complement to reconstructive surgery. PMID- 8506469 TI - [Osteochondroma of the mandibular condyle. Apropos of a case]. AB - The authors report a case of mandibular condyle osteochondroma on a 33 years-old woman, similar to osteocartilaginous exostosis of the long bones. The lesion was revealed by a facial asymmetry and a change of the occlusion. The diagnosis was performed on the computed-tomography examination and histopathology. The removal of the lesion has conserved the condyle without recurrence after 20 months following-up. The authors remind the uncommonly location of osteochondroma in the facial skeleton and discuss the histogenesis of this lesion in its mandibular condyle site. PMID- 8506470 TI - [Primary malignant non-Hodgkin's lymphoma of the salivary glands. An anatomo clinical and immunohistochemical study of 2 cases and a review of the literature]. AB - The authors reports two cases of primary non Hodgkin's lymphomas of the right submandibular gland in a 50 years old woman, and of a minor gland in another woman also 50 years old. The diagnosis was difficult for the second case, and was established on the immunochemistry study. The authors discuss the epidemiological, clinical, radiological, pathological features of this neoplasm and its management. PMID- 8506471 TI - The surgical correction of the injured nose. A follow up study of 243 cases in 12 years. AB - Due to its prominent position the nose is very often involved in facial traumas. Even minor injuries may cause major disturbances of form and function. Thus, a nasal injury should regularly be treated primarily. Planned secondary corrections are indicated only in rare exceptions. PMID- 8506472 TI - [Selenium in the serum of healthy and diseased calves]. AB - Between 1988 and 1990, selenium concentrations were measured in the serum of 188 calves admitted for various conditions to the University of Zurich veterinary hospital, and in 64 healthy calves that served as controls. The lowest mean concentration was measured in the controls and it was 14.5 micrograms/L. The mean concentrations in patients not previously supplemented with selenium for the three years were 29.1, 27.5 and 23.0 micrograms/L, respectively, and the concentrations in the patients after supplementation were 61.7, 88.7 and 72.6 micrograms/L, respectively. The differences between the two groups of patients, and between controls and calves of 1989 without selenium supplementation were statistically significant (P < 0.05). There were no significant differences between mean selenium concentrations of calves of different age groups or between calves of different disease groups. Selenium concentrations were not correlated with blood pH, plasma protein and fibrinogen concentrations. The low values measured in untreated calves paralleled results of previous studies in calves and cows in Switzerland. PMID- 8506473 TI - [The "hemorrhagic bowel syndrome" of swine: clinical, pathologo-anatomic and etiopathogenic aspects]. AB - In an analysis of autopsy findings from 16,384 pigs (1980-90) 436 cases of haemorrhagic bowel syndrome (HBS) were found (2.66% of autopsies). In most cases fattening pigs (in the weight of 25-100 kg) were affected. HBS was significantly more frequent in females. Intestinal volvulus was confirmed in 56.2% of all cases of HBS, however by more careful examination between 1988 and 1990 even in 80% of cases. In most cases the degree of torsion was 180 degrees and the direction as seen with the pig lying on its back was anticlockwise. Clinical history as reported by owners revealed limited information: sudden death of one or several pigs within three months, association with whey feeding not uncommon. Significantly more cases of HBS were seen during spring and on mondays. Numerous yeasts could be detected in mucosal impression smears of ileum, colon and caecum. Additional analyses in six farms suffering from big losses due to HBS suggested that several environmental and management factors may be involved pathogenetically: feeding only once a day of excessive amounts of a liquid diet, especially whey (a highly fermentable substrate), poor hygiene of liquid diets (high bacterial counts and yeast concentrations). In mixed breeding and fattening units, the aforementioned factors could be responsible also for sudden deaths in dry sows caused by colonic bloat often associated with intestinal rupture and torsions of the stomach and/or the spleen. PMID- 8506475 TI - [Environmental protection in veterinary practice]. PMID- 8506474 TI - [What is your diagnosis? What treatment do you suggest?]. PMID- 8506476 TI - Is a Hemoccult-positive rectal examination clinically significant? AB - To determine the clinical significance of finding occult blood in a stool sample obtained during digital rectal examination of patients with no gastrointestinal complaints, we reviewed the records of patients who had colonoscopy for this indication. Of the 185 patients (average age, 59.4 years) who met study criteria, 48 were inpatients when the Hemoccult-positive rectal examination was recorded. Neoplastic lesions were found in 28% of the patients (51/185). Thirteen of the lesions were adenocarcinomas and 38 were adenomatous polyps. Seventy-five patients (41%) had normal findings on colonoscopy. Nonneoplastic lesions were found in the remaining 32%. Comparison of patients with neoplastic lesions and patients with nonneoplastic lesions showed no significant difference with respect to the presence of anemia (43% vs 48%), inpatient status at the time of positive rectal examination (23% vs 29%), or sex. Although the mean age was similar in patients with and without neoplastic lesions (60.5 and 56.8 years, respectively), no neoplastic lesions were found in patients less than 45 years old. We conclude that testing stool obtained during rectal examination for occult blood does not increase the rate of false-positive results, and positive test should prompt a structural evaluation of the colon to detect neoplasia in patients with an age related risk for colon carcinoma. PMID- 8506478 TI - Chlamydial cervical infections in rural and urban pregnant women. AB - The purpose of this investigation was to determine the incidence of cervicitis due to Chlamydia trachomatis in rural pregnant women, urban pregnant women, and urban nonpregnant women in Georgia. Evaluation of endocervical chlamydial cultures from 447 women showed prevalence rates for C trachomatis cervicitis of 12% in the urban pregnant group, 7% in urban nonpregnant women, and 21% in rural pregnant women. Fewer rural pregnant women (2%) reported a previous history of C trachomatis cervicitis than urban pregnant women (9%) and urban nonpregnant women (19%). Data from this study imply that screening for C trachomatis may be done less frequently in rural women than in urban women. The high prevalence of C trachomatis infection observed in rural pregnant women emphasizes the importance of routinely screening this group as currently recommended. Laboratory testing for C trachomatis may be overlooked because of insufficient funds and an emphasis on other sexually transmitted diseases. PMID- 8506477 TI - Multicenter randomized trial of ofloxacin versus cefoxitin and doxycycline in outpatient treatment of pelvic inflammatory disease. Ambulatory PID Research Group. AB - A multicenter randomized comparative trial was done to assess the safety and efficacy of oral ofloxacin (400 mg twice daily for 10 days) versus cefoxitin (2 g intramuscularly) followed by doxycycline (100 mg twice daily orally for 10 days) for the outpatient treatment of uncomplicated pelvic inflammatory disease (PID). Neisseria gonorrhoeae (GC) grew on pretreatment endocervical cultures from 43 of 268 women (16%), and in 30 of 247 women (12%) cultures were positive for Chlamydia trachomatis (Ct). Ninety-five percent (122/128) of the women treated with the ofloxacin regimen and 93% (112/121) of those treated with the cefoxitin/doxycycline regimen had cure or improvement on examination at a minimum of one follow-up visit. All GC species were eradicated by both ofloxacin and cefoxitin. Among women who returned for follow-up, the eradication of C trachomatis was 88% (15/17) for the cefoxitin/doxycycline group and 100% (18/18) for ofloxacin. Side effects were more prevalent in the cefoxitin/doxycycline group (15%) than in the ofloxacin group (7%), nausea/vomiting being the most frequent adverse effect. In this study, it appears that ofloxacin and cefoxitin/doxycycline have similar clinical effectiveness for the outpatient treatment of uncomplicated pelvic inflammatory disease. PMID- 8506479 TI - Group A streptococcal bacteremia in a mid-south children's hospital. AB - We reviewed microbiology and infection control records at a Memphis children's hospital from 1982 to 1990 to obtain epidemiologic, clinical, and microbiologic data on group A streptococcal (GAS) bacteremia. Varicella was the underlying condition in 8 of 37 (22%) patients identified and was often associated with severe GAS disease, including toxic shock-like syndrome. Twenty-one of 31 (68%) available blood isolates made GAS pyrogenic exotoxin (SPE) B by Ouchterlony immunodiffusion; gene probes identified speC and speA in 18 (58%) and 8 (26%) isolates, respectively. The B/C toxin profile, identified in 11 (35%) isolates, was the most common profile in this population, and the overall rate for speC was higher than rates recently reported from other areas. Although the clinical significance of the toxin profiles in our population is unclear, these data emphasize the geographic and temporal variability in the microbiologic properties of GAS disease. PMID- 8506480 TI - Laparoscopic management of ectopic pregnancy in a resident training program. AB - The range of procedures now routinely done through the laparoscope has continued to expand due to improved equipment for insufflation, hemostasis, and tissue manipulation, and to imaginative approaches to otherwise "routine" gynecologic problems traditionally treated by laparotomy. As with all new technologies, advocates predict that the methodology will prove to have an almost unlimited potential, while established skeptics predict that it will have a narrow applicability. With time and further clinical application, a consensus somewhere between the two positions will be reached. But while this technology develops and experience begins to accumulate, it is necessary to train residents in the technique. We discuss our experience with introducing laparoscopic management of ectopic pregnancy into a residency training program. Our results indicate a rapid learning curve, with minimal patient morbidity, brief hospitalization, and rapid convalescence. PMID- 8506481 TI - Acute upper airway obstruction resulting from systemic diseases. AB - Acute upper airway obstruction is usually associated with inflammatory processes such as epiglottitis, and with laryngeal trauma and laryngeal tumors. Not uncommonly, systemic diseases such as Wegener's granulomatosis and sarcoidosis may manifest initially as upper airway obstruction requiring intubation or tracheostomy. We describe our experience in the diagnosis and management of cases of airway obstruction due to previously undiagnosed systemic diseases. We believe that physicians should be familiar with the airway manifestations of these systemic diseases when treating patients with airway distress of apparently unknown cause. PMID- 8506482 TI - Optimal use of beta irradiation in the treatment of pterygia. AB - Beta irradiation with strontium 90 has been associated with significant iatrogenic disease, causing such complications as ptosis, symblepharon, iridic and scleral atrophy, cataracts, and endophthalmitis. We studied 171 eyes in 140 patients treated and followed up during a 17-year period from 1973 to 1990. We sought to show that a single small dose of radiation administered immediately after surgical excision not only prevents decrease recurrence, but also avoids significant complication. Pterygia recurred in 14 (8%) of the 171 eyes treated. Six of these recurrences were corneal and eight were conjunctival. Complications were seen in five (3%) of the 171 eyes treated. All were minor except for one case of scleral thinning in a diabetic patient. Optimal radiation dosage to avoid significant recurrence in this adult population is a single dose of 2,000 rads using a bare sclera technique that vaults the limbus. PMID- 8506483 TI - Nontuberculous mycobacterial infection of the central nervous system in patients with AIDS. AB - Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases. Of these, 15 were caused by Mycobacterium avium-intracellular (MAI), and one was caused by M fortuitum. All patients with MAI infection had widespread dissemination and at least one risk factor for AIDS. Clinical features included weight loss, altered mentation, and seizures. Analysis of cerebrospinal fluid revealed a mildly elevated leukocyte count with lymphocyte predominance and normal protein and glucose values. All direct smears were negative for acid-fast bacilli. In-hospital mortality was 67%. The patient with infection due to M fortuitum had a preexisting diagnosis of AIDS and had a right upper lobe pneumonia and headaches. Cranial CT showed an enlarged infundibulum of the pituitary gland. Results of CSF analysis were essentially normal, and direct smears were negative. He left the hospital against medical advice. Our study indicates that the finding of MAI in the CSF in patients with AIDS is associated with an in-house mortality of 67% indicating a very poor prognosis. PMID- 8506484 TI - Nonulcer dyspepsia associated with psychiatric disorder. AB - Studies of dyspepsia show a 1% to 2% prevalence in adults, and 25% to 40% of these patients do not have a physical reason for their symptoms. These findings prompted us to do a retrospective follow-up study of 390 patients having motility studies for chest pain and gastrointestinal (GI) symptoms; 278 (71%) responded. Patients were asked to complete a self-rating symptom questionnaire regarding current GI symptoms and current symptoms of anxiety, panic, and depression; they were also asked to complete the Brief Symptom Inventory. Two groups were compared -those with known heart disease and those without heart disease. Substantial numbers of patients in both groups satisfied criteria for generalized anxiety disorders (> 70%), panic disorder (> 30%), and major depression (> 35%). GI symptoms compatible with nonulcer dyspepsia were strongly associated with a psychiatric diagnosis. Our data suggest that anxiety and depressive states are strongly associated with dyspepsia and other GI symptoms not caused by ulcer disease. PMID- 8506485 TI - Epidemiologic and clinical aspects of shigellosis in American forces deployed to Saudi Arabia. AB - I describe nine cases of shigellosis seen at a large Navy field hospital in troops deployed to Saudi Arabia during the Gulf War. Eight cases were associated with consumption of food at civilian restaurants or civilian-contracted food services. Two adults had "pseudomeningitis" syndromes, illustrating that shigellosis in adults may initially be misdiagnosed. All patients responded rapidly to rehydration and oral fluoroquinolone (ciprofloxacin) therapy. Five patients received an antimotility agent without apparent adverse effect. PMID- 8506486 TI - Bioimpedance measurement of body water correlates with measured volume balance in injured patients. AB - Bioimpedance technology is being used increasingly to determine drug volume of distribution, body water status, and nutrition repletion. Its accuracy in patients experiencing large volume flux is not established. To address this, we undertook this prospective study in 54 consecutive seriously injured adults who had emergency celiotomy soon after arrival in the emergency department. Bioimpedance measurements were obtained in the emergency department before the patient was transported to the operating room, on completion of celiotomy, and 24 hours and 48 hours after celiotomy. Bioimpedance measurements of body water were compared with measured fluid balance. If insensible losses are subtracted from measured fluid balance, the percentage of body weight, which is body water determined by bioimpedance, closely follows fluid flux. This study supports the use of bioimpedance measurements in determining total body water even during periods of surgery, blood loss, and vigorous resuscitation. PMID- 8506487 TI - Home exposures to chlorine/chloramine gas: review of 216 cases. AB - Chlorine and chloramine gas are frequently produced in the home when cleaning products are mixed. These gases are strong irritants with the potential for tissue damage. Numerous literature citations report industrial exposures to chlorine/amine gas, but there are few reports regarding home exposures. The purpose of this study was to determine symptoms, treatment, and outcome in individuals exposed to these gases in the home. All exposures to chlorine/amine gas produced as a result of mixing cleaning products in the home and reported to a Regional Poison Information Center (RPIC) over a 12-month period were reviewed. All calls were documented and follow-up was done at appropriate intervals. All patients with respiratory embarrassment either at the initial contact or on follow-up were referred to a medical facility. Of the 216 patients (ages 12 to 81 years), 200 had resolution of symptoms within 6 hours, whereas only 16 had symptoms for more than 6 hours after exposure; 145 patients were treated at home and 71 received further medical care. Ten symptoms were identified, with the majority of patients experiencing more than one. Emergency room treatment included oxygen (62 patients), bronchodilators (9 patients), and steroid therapy (3 patients). Of the 70 patients who had chest x-ray films, only one had a positive finding; 41 had arterial blood gas measurements done, and all were within normal limits. Only one patient in the study group required admission for continued respiratory distress, but he had a preexisting chronic respiratory problem as well as an upper respiratory tract infection at the time of exposure. Although the gas produced by mixing cleaning products in the home can cause severe respiratory irritation, most of the patients exposed to chlorine and chloramine gas can safely be treated at home with comfort measures. Appropriate follow-up must be done to determine resolution of symptoms. PMID- 8506488 TI - Predicting severity of trauma by admission white blood cell count, serum potassium level, and arterial pH. AB - Traumatized patients frequently have leukocytosis, hypokalemia, and acidosis. The purpose of this study was to determine whether the admission serum potassium level (K+), white blood cell count (WBC), and arterial pH predicted the severity of injury in trauma patients. The injury severity score (ISS), total length of stay in the hospital (tLOS), and length of stay in the intensive care unit (LOS ICU) were used to measure the severity of the injury. The charts of 156 consecutive trauma patients admitted to a level II trauma center were reviewed. Acidosis (arterial pH < 7.35) was associated with an increased mean ISS, tLOS, and LOS-ICU. Leukocytosis (WBC > or = 10,500/mm3) correlated with a higher mean ISS, and LOS-ICU. Patients with hypokalemia (K+ < 3.6 mEq/L) had an increased mean ISS and tLOS. Our findings suggest that the admission white blood cell count, serum potassium level, and arterial pH have a predictive value as to the severity of injury. PMID- 8506489 TI - Assessment of medical students' knowledge regarding human immunodeficiency virus transmission: comparisons by gender, residence, and training level. AB - As the incidence of human immunodeficiency virus (HIV) infection increases, health care practitioners are being called upon to counsel and educate patients regarding the complications associated with HIV infection. In addition, the anxiety levels of health care workers reveal that similar educational efforts must be initiated early in the training of health care professionals. In this study we surveyed 341 first and second year medical students from three medical schools to assess their levels of knowledge about how HIV infection is and is not transmitted. Results were analyzed overall, by site, by gender, and by the respondents' locality (urban or rural). Analysis revealed that knowledge regarding HIV transmission varied dramatically among these first and second year medical students. Place of residence, gender, and class rank did not appear to be factors affecting these students' knowledge. We recommend that caution be exercised in assuming that prospective physicians possess current knowledge on how HIV infection is transmitted. PMID- 8506490 TI - Impact of treating involuntarily admitted schizophrenics on an open unit. AB - When involuntary psychiatric patients are treated on unlocked units, problems may arise as to resource expenditure and the ability to provide optimal psychiatric care. This study investigates the problem and possible solutions. PMID- 8506491 TI - Surgical treatment of Meckel's diverticulum. AB - Meckel's diverticula are the result of incomplete degeneration of the vitelline duct. It is generally believed that less than 5% of them become symptomatic, the frequency decreasing with age. Meckel's diverticula are most commonly manifested in children by painless lower gastrointestinal bleeding and in adults, as an inflammatory process or obstruction. Definitive diagnosis is usually made at surgery, though the Meckel's scan may suggest a diagnosis preoperatively, especially in the pediatric population. All symptomatic and pathologic Meckel's diverticula should be removed with a segment of ileum. The use of stapling devices, with their ease of use and low complication rate, make it reasonable to remove any Meckel's diverticulum that easily fits in the device. If a diverticulum found incidentally is so broad-based or short that stapling cannot be done without difficulty, it is unlikely to become symptomatic and should be left undisturbed. PMID- 8506492 TI - Asphyxial brain damage in the newborn: new insights into pathophysiology and possible pharmacologic interventions. AB - New insights into the pathophysiology of the hypoxic-ischemic insult have opened the possibility of pharmacologic intervention in neonatal hypoxic-ischemic encephalopathy. It is now known that many neurons survive a hypoxic-ischemic insult but remain dysfunctional for hours, with profound alterations in cell function. A cascade of biochemical alterations occurs as a consequence of cellular ionic shifts, energy depletion, degradation of cell membrane phospholipids, and increased release of neurotransmitters. In addition, there are alterations in the metabolism of arachidonic acid and prostanoids and an excessive production of oxygen free radicals. The new therapeutic modalities are aimed at preventing or arresting the biochemical changes that occur in the period after hypoxia-ischemia. This review details the biochemical alterations associated with neonatal hypoxic-ischemic encephalopathy and discusses the possible use in newborns of pharmacologic agents currently undergoing extensive investigations in experimental animals and adult humans. PMID- 8506493 TI - Chronic salicylate intoxication. AB - Physicians should question their elderly patients and those who know their life styles and habits best (ie, family, friends, caretakers) regarding use of over the-counter medications. Salicylates are commonly used by the elderly, and long term unsupervised use may lead to salicylate toxicity that can cause delirium. In the southern United States, BC and Goody's Headache Powders are widely marketed and used, and their overuse can produce salicylate intoxication. PMID- 8506494 TI - Polycythemia as a complication of human immunodeficiency virus infection. AB - HIV infection is commonly associated with cytopenias. The occurrence of erythrocytosis is rare, with only one report in the medical literature. We have described the case of an asymptomatic patient found to be seropositive for HIV. The blood counts were initially normal except for mild eosinophilia and thrombocytopenia. Over the next 18 months erythrocytosis developed and thrombocytopenia worsened. Workup at that time revealed elevated red cell mass, suppressed erythropoietin, normal arterial oxygen saturation, and splenomegaly documented by abdominal computed tomography. Zidovudine therapy was started in April 1990, when the CD4 cell count dropped below 500/mm3. Over the next 4 months the hematologic indexes returned to normal levels. The patient remains asymptomatic. PMID- 8506495 TI - Concurrent verrucous carcinomas of the lip and buccal mucosa. AB - Florid oral papillomatosis presents a picture of multiple squamous papillary lesions found in the oral pharynx. Multiple risk factors associated with the development of these lesions include possible association with papilloma virus, the use of tobacco products, and chronic inflammation or irritation such as that caused by poorly fitted dentures. The major risk factor of these benign squamous lesions is the dedifferentiation into a well-differentiated verrucous carcinoma. However, treatment in the early stage of the disease is usually successful. Surgical excision has been favored as the initial approach. The use of radiotherapy for verrucous carcinoma is controversial. In numerous reported cases dedifferentiation of the tumor has produced an anaplastic squamous cell carcinoma. More recent articles, however, indicate that the risk for dedifferentiation of verrucous carcinoma due to radiotherapy may be overstated. PMID- 8506496 TI - Perplexing pericarditis caused by coccidioidomycosis. AB - In the patient I have described, evaluation of chronic progressive pulmonary coccidioidomycosis presenting itself as cryptogenic pericarditis revealed an unsuspected large endobronchial coccidioidoma. At follow-up after 2 years of fluconazole therapy, the patient was asymptomatic, with a dramatic decrease in infiltrate but no change in CF titers. In endemic areas, coccidioidomycosis should be included in the differential diagnosis of idiopathic pericarditis, especially in high-risk patient populations. Additionally, airway obstruction or compromise might be an early finding in chronic coccidial disease. PMID- 8506497 TI - Recurrence of rectal carcinoma in the mediastinum. AB - Mediastinal metastases arising from a primary gastrointestinal neoplasm usually follow extensive subdiaphragmatic spread. However, we have reported the rare recurrence of rectal carcinoma in the mediastinum. In addition to emphasizing the systemic metastatic spread of rectal carcinoma, this case demonstrates the need to consider metastases arising from abdominal tumors as a cause of mediastinal masses. PMID- 8506498 TI - Guillain-Barre syndrome due to swine influenza and neurologic damage due to DTP vaccines: the touch of statistics. PMID- 8506499 TI - Time for a health care equation for good health. PMID- 8506500 TI - Dizzy medical writing and editing: a decade of non-progress. PMID- 8506501 TI - A last martyr of the conquest of yellow fever. AB - The last of six Rockefeller Foundation investigators to die studying yellow fever was Theodore B. Hayne, 31 years old and recently married. He had returned to hazardous duty in West Africa knowing of the deaths of four other investigators within the previous 3 years. PMID- 8506502 TI - Squamous cell carcinoma of the breast. PMID- 8506503 TI - Victims of crime. PMID- 8506504 TI - Sources of variation in spirometric measurements. Identifying the signal and dealing with noise. AB - Variation in spirometric lung function measurements can be ascribed to technical and biological sources and is conveniently classified as within- or between subject and within- or between-population. A necessary first step is to identify which sources of variation constitute "noise" and which "signal" in the various applications in occupational medicine. This chapter proposes strategies to enhance signal and deal with noise, and it delineates areas in which additional research to strengthen existing information would maximize the usefulness of spirometric measurements. PMID- 8506505 TI - Application of peak expiratory flow in epidemiologic studies of occupation. AB - Investigation of the use of PEF in the measurement of airway variability over a single day or several weeks suggests that serial measures of PEF may prove useful in detecting short-term adverse responses to a variety of environmental agents. Several investigators have already shown how the visual inspection of temporal trends can prove useful in identifying individuals with occupational asthma. The use of statistical summaries of diurnal variation, i.e., the amplitude as a percent of the daily mean, may provide important added information about airway reactivity in response to occupational exposures in a variety of populations. Indeed, there are several groups of investigators presently examining more refined ways, including autoregressive time series models, of linking short-term temporal patterns in serial measurements of PEF with simultaneously measured short-term exposures. As our understanding of the sources and nature of the variability in PEF improves, together with refinements in the statistical techniques used to describe the temporal data, serial measures of PEF are likely to see a far broader application in the study of acute respiratory hazards. Does the utility of PEF as a pulmonary function measurement stem solely from ease of collection and the consequent increase in the amount of data one can gather, or is the PEF a distinctly different and inherently useful measure of pulmonary function? This question cannot yet be answered. The increasing availability of accurate reliable hand-held spirometers means that one can now plan studies using the powerful repeated measures designs previously feasible only with the peak flow meter (see article on Instrumentation, pp 397-408, in this issue). These data will enable side-by-side comparisons of PEF, FEV1, maximum mid-expiratory flow, and other parameters collected simultaneously. Will the FEV1 once again become the preferred measure of airflow? Time will tell. PMID- 8506506 TI - Use of serial measurements of peak flow in the diagnosis of occupational asthma. AB - Occupational asthma is best verified by physiological measures, including (1) measurement of lung function on a single occasion with bronchodilator response, (2) measurement of lung function before and after a workshift, and (3) repeated measurement of PEF over long periods of time, including readings at and away from work. The author describes a qualitative method for distinguishing patterns of PEF change at and away from work which has been effective in the diagnosis of work-related asthma. PMID- 8506507 TI - Reproducibility of peak expiratory flow measurements. AB - The ease of PEF measurement and the availability of inexpensive, portable instruments have led to its increasing use. However, relatively little literature exists addressing the testing procedure, optimal frequency, instrument precision, and virtually no epidemiologic literature exists describing the variability of repeated PEF tests within a single test session (reproducibility). A summary of data from one of the authors' own worker population studies is presented which addresses precision of PEF measurement. PMID- 8506508 TI - Measurement of nonspecific bronchial responsiveness in epidemiologic studies: methacholine challenge testing in the field. AB - Methacholine challenge testing is the most commonly used method for detecting and quantifying nonspecific bronchial hyperresponsiveness and has been used primarily in the clinical investigation of occupational asthma. This chapter reviews the rationale, methodology, and interpretation of this test which are relevant to conducting methacholine challenge testing outside the clinic ("in the field"). It also reviews the issues surrounding the methodology of methacholine challenge testing in general and, in particular, its use in epidemiologic studies. PMID- 8506509 TI - Percentile curves for evaluation of repeated measures of lung function. AB - Methods are discussed for evaluating repeated measures of an individual's lung function over time, based on the concept that the best estimate of a subject's lung function at any time is a previous measurement of his or her lung function. Rather than considering change in lung function measurements over time, individuals are evaluated based on the degree that their lung function tracks along fixed percentiles within a reference population. Measures of FVC and FEV1 are focused upon. PMID- 8506510 TI - Reconciling cross-sectional with longitudinal observations on annual decline. AB - In summary, numerous factors may contribute to observed differences between longitudinally and cross-sectionally derived measures of annual decline in lung function. The direction and magnitude of these differences appear hard to predict. Furthermore, although these differences can be minimized by careful modeling of the data, they cannot, in general, be completely avoided. It seems plausible, however, that both types of studies should give similar qualitative comparisons of risk factor effects if appropriately modeled. Longitudinal studies are likely to provide the most accurate and reliable estimates of lung function decline for both individuals and populations. Such data may be especially useful in identifying individuals with accelerated declines in lung function but who still have "normal" lung function as measured cross-sectionally. However, such studies require careful attention to quality control and typically require at least 4 years of follow-up before the noise in the data settles down. Multiple measurements, preferably four or more, are also necessary to reliably detect and adjust for survey effects. Cross-sectional studies, on the other hand, are simpler, cheaper, and quicker to conduct than are longitudinal studies. They may be particularly useful as a screening tool for identifying potentially affected or high-risk subjects (e.g., those with low levels of lung function) who may require further medical follow-up and/or ongoing monitoring. Both types of studies have a role in population-based occupational health hazard assessments. PMID- 8506511 TI - Medical screening using periodic spirometry for detection of chronic lung disease. AB - Approximately half of a worker population may benefit from the addition of a longitudinal comparison of their spirometry results, over only using annual comparisons with a cross-sectional LLN. The ATS recommendation of 15% for year-to year changes appears to be essentially equivalent to a longitudinal LLN method based on the SEE. Therefore, a practical method for longitudinal interpretations is to establish a baseline value for a worker's FEV1 through several initial spirometric examinations. The FEV1 longitudinal LLN is calculated by taking 85% of this baseline value minus the expected decline over the time period based on the individual's age (e.g., for individuals older than 35 years at their initial examination, one approach is to use 30 mL/year times the number of years of follow-up). However, before any final classification is rendered, the data should be reviewed for stability. This analysis demonstrates that longitudinal spirometry adds sensitivity to spirometry screening efforts. The spirometry examinations should probably be performed annually in order to detect survey biases and determine the stability of the FEV1 measurements. If spirometry results indicate that someone has crossed either the longitudinal or the cross sectional LLN, intervention activities should be initiated for that individual. As new data and studies become available, these suggested procedures will need to be revised-particularly estimates for the expected annual decline in FEV1. PMID- 8506512 TI - The relation between chronic respiratory symptoms and ventilatory capacity in adults. AB - In the clinical setting, a patient's chronic respiratory complaints often provide the first clue of underlying lung disease. Chronic symptoms may themselves be important or may complement objective measures of spirometry in assessing respiratory status. This chapter focuses on one aspect of chronic symptom reporting--the efficacy of standardized symptom questionnaires in respiratory epidemiology--and reviews the reliability of reported symptoms as well as evidence for the relation between chronic symptoms and diminished ventilatory capacity as measured by spirometry. PMID- 8506513 TI - Measures of small airways disease as predictors of chronic obstructive pulmonary disease. AB - Deficits in FEV1 and FVC have been shown to correlate with the presence of occupationally related obstructive and restrictive lung disease, but significant changes do not occur in the two parameters until these diseases are already well established. The current understanding of the relationship between small airways testing and the subsequent development of COPD is reviewed. Various methods for evaluating peripheral airways are discussed, with emphasis on applicability in the field, reliability and reproducibility, and technical aspects of testing. PMID- 8506514 TI - Instrumentation for spirometry. AB - In addition to improvements in spirometry instrumentation, the availability and quality of mechanical pump-testing equipment have also improved. These devices have largely relied on the ATS 24 standard waveforms and appear to simulate human FVC maneuvers reasonably well, at least with respect to testing using room air. Testing using mechanical pumps filled with heated and humidified air to better simulate the human FVC maneuver is still evolving. With the availability of these testing devices, many problems in both spirometric hardware and software can be identified and corrected. Perhaps the two most significant emerging advancements in spirometry instrumentation are the automated test acceptability and reproducibility assessments with immediate feedback to the technician and the development of small portable spirometers. At least two major studies (LHS8 and NHANES12) have described a second generation of comprehensive on-line assessment of test quality with immediate feedback to the spirometry technician. The use of quality assessment software appears to significantly improve the quality of the spirometry data through feedback to technicians. Spirometry hardware is also advancing as several hand-held devices are being developed to measure not only peak flow but also FEV1, FVC, and other parameters. These battery-powered portable spirometers will continue to decrease in size and cost and may eventually displace the hand-held peak flow meters in current use. PMID- 8506515 TI - Ileal pouch-anal anastomosis: current status and controversies. PMID- 8506516 TI - Blood transfusions and postoperative wound infection. AB - BACKGROUND: Several studies have suggested an association between blood transfusions and infection in surgical patients. However, previous reports have not documented the relationship of transfusion to specific infection sites and have not adequately explored the importance of timing and type of blood product. METHODS: We reviewed the records of all patients undergoing operation for colon cancer at a large community hospital during the years 1974 to 1987. Data on hospital wound and other infections, wound infection risk factors, and type and timing of transfusions were analyzed. RESULTS: Increased wound infection rates were associated with administration of both whole blood and packed red blood cells. However, multivariate analysis suggested that only the administration of packed red cells after operation independently predicted wound infections. Other independent variables were the presence of a colostomy and/or drain. A highly predictive model for wound infection was constructed with these three variables. CONCLUSIONS: Blood transfusions, especially with packed red cells, after operation are an independent risk factor for wound infection. PMID- 8506517 TI - Trauma is a recurrent disease. AB - BACKGROUND: Many victims of trauma have a history of repetitive accidental or violent injuries, which implies that trauma is not necessarily a random event. Recurrent trauma is thought to be a problem of urban areas, associated with criminal activities, but there are few data from rural areas that include the victims of nonintentional injuries. METHODS: The prior trauma experience of 200 consecutive patients admitted for trauma was compared with that of 100 consecutive emergency nontrauma surgical admissions and 100 elective surgical admissions to a university hospital and level I trauma center. RESULTS: Trauma patients were younger than emergency patients and elective surgery patients. They were more likely to be male than either emergency or elective surgery patients and, along with emergency nontrauma patients, were more likely to be from a racial minority than were elective admissions. Trauma patients were more likely to have had a previous hospitalization for an injury than either emergency patients or elective surgery patients, and a greater proportion of their prior trauma admissions had been within the past 5 years than in the other two groups. There was no difference in the probability of a prior trauma admission between patients admitted with an intentional injury or an accidental injury, but patients whose current admission was for an intentional injury were three times more likely to have had a prior hospitalization as a result of an intentional injury than were patients admitted because of an accidental injury. CONCLUSIONS: Trauma is a disease with a high risk of recurrence. This may be related to chronic high-risk behaviors such as alcohol or drug abuse, preexisting psychopathology, and cultural acceptance of violent resolution of personal conflicts, all of which adversely affect patients' lives. The role of intensive preventive measures after an initial injury, and directed toward specific high risk behavior, should be evaluated. PMID- 8506518 TI - Failure of cimetidine to reduce postoperative hypocalcemia in patients with primary hyperparathyroidism undergoing neck exploratory operation. AB - BACKGROUND: Although use of histamine H2 antagonists for chronic treatment of primary hyperparathyroidism (PHP) is ineffective, pretreatment with cimetidine has been reported to reduce the incidence of postoperative hypocalcemia in patients with PHP undergoing neck exploratory operation. The current investigation was conducted to determine the validity of this assertion. METHODS: In a randomized, double-blind, placebo-controlled trial, 20 patients with PHP were treated with either cimetidine or placebo for 10 to 14 days before neck exploratory operation. Clinical outcome and biochemical indexes before and after drug treatment in both groups were compared. RESULTS: Cimetidine treatment resulted in a modest increase in preoperative parathyroid hormone level but did not affect any other parameter, including serum calcium level or renal tubular reabsorption of phosphate. Intraoperative time was similar in both groups. Mean postoperative calcium nadir was identical regardless of therapy (8.3 mg/dl), and seven (70%) patients from each group had at least one serum calcium measurement less than 8.5 mg/dl. CONCLUSIONS: Cimetidine treatment before neck exploratory operation for PHP does not diminish the frequency or severity of postoperative hypocalcemia. PMID- 8506519 TI - Activation state of polymorphonuclear leukocytes in surgical patients: characterization of surface receptor expression. AB - BACKGROUND: We studied the expression of chemotactic, opsonic, and adherent receptors on the membranes of polymorphonuclear neutrophils (PMNs) from surgical patients because modulation of these receptors has been suggested in the control of critical PMN functions that directly or indirectly influence patient outcome. METHODS: Healthy subjects who had PMN adherence, chemotaxis, and receptor measurements were compared with preoperative surgical patients and those who were within 48 hours of an admission to an intensive care unit (surgical intensive care unit) because of an acute illness. RESULTS: The following receptor/cell pattern was found in control subjects, preoperative patients, and patients in the surgical intensive care unit, respectively: formyl peptide (13,000 vs 18,000 vs 22,000), CR3 (59,000 vs 105,000 vs 121,000), fibronectin (21,000 vs 20,000 vs 35,000), FcII gamma (9,000 vs 20,000 vs 25,000), C5a (347 vs 265 vs 250 mean channel number), and FcIIIR (64,000 vs 75,000 vs 26,000). This receptor pattern was partly correlated directly or indirectly with the acute-phase response, neutrophil adherence, and PMN chemotaxis from these subjects. CONCLUSIONS: The data suggest that there are alterations in the expression and modulation of PMN surface membrane receptors in patients with a "stable" disease process compared with those with an acute illness, which may affect critical PMN functions needed to combat bacterial infections. PMID- 8506520 TI - Morbidity and mortality of cytoreductive surgery and intraperitoneal chemotherapy. AB - BACKGROUND: Peritoneal carcinomatosis has been regarded as a uniformly lethal clinical entity. Recently, dose-intensive treatments combining cytoreductive surgery and intraperitoneal chemotherapy have resulted in long-term survival in selected patients. METHODS: This article reports the morbidity and mortality associated with this new treatment strategy in 45 consecutive treatments of 43 patients with peritoneal carcinomatosis treated during an 18-month interval. RESULTS: The duration of median postoperative ileus was 21 days, and increased age of the patient and extent of cytoreduction caused an increased incidence of ileus. Twenty-one complications occurred in 17 patients (37.7%). Complications related to enteric function included fistula (n = 4), bile leak (n = 1), pancreatitis (n = 1), and anastomotic disruption (n = 1). There were two early and two late episodes of postoperative bleeding requiring reoperation. Six patients had pneumonia and one had deep vein thrombosis. There were no deaths. Six of the seven complications related to enteric function occurred in patients who had undergone induction intraperitoneal chemotherapy before cytoreductive surgery plus early postoperative intraperitoneal chemotherapy. CONCLUSIONS: As a result of these findings, induction intraperitoneal chemotherapy is only recommended for patients with low-volume intraabdominal cancer. In most patients surgical removal of peritoneal carcinomatosis before intraperitoneal chemotherapy is recommended. Because of the significant morbidity related to treatment of peritoneal carcinomatosis, careful patient selection and favorable long-term results of treatment are required. PMID- 8506521 TI - Extracorporeal hepatic resection for previously unresectable neoplasms. AB - BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past. PMID- 8506522 TI - Evaluations of surgery resident performance correlate with success in board examinations. AB - BACKGROUND: American Board of Surgery (ABS) In-Training Examination (ABSITE) scores correlate with future examination scores, but faculty evaluations of resident skill have not been shown to predict future performance. METHODS: Objective and subjective evaluations during the past 15 years in our columnar university surgical residency were reviewed to assess their ability to predict success on the qualifying (written) and oral (certifying) examinations offered by the ABS. RESULTS: The ABSITE scores correlated with success on the qualifying examination (multiple R2 = 0.473). Subjective assessments of resident knowledge at any level did not correlate with ABSITE or qualifying scores, but above average scores did predict success on the certifying examination (chi 2, p < 0.005). Chief-year ABSITE total percentile score and score of first qualifying examination also predicted success on the certifying examination. The attrition rate in our nonpyramidal program was 23%, of which more than one half were voluntary. One of 11 residents leaving the program has subsequently attained ABS certification. CONCLUSIONS: This study shows that faculty's subjective evaluations predicted resident success on the ABS certifying examination and also endorses the ABS oral examination as an effective measure of the candidate's ability to communicate surgical knowledge. PMID- 8506523 TI - Parathyroid hormone secretion after operation for primary hyperparathyroidism. AB - BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with a defective regulation of the secretion of parathyroid hormone (PTH). Thus in pHPT, higher than normal calcium concentrations are required to inhibit PTH release. However, it is not known if this defective regulation is normalized by removal of the parathyroid adenoma (i.e., whether the regulation of PTH secretion is normal in the remaining glands). In this study we therefore investigated the PTH secretion in patients operated on for parathyroid adenoma 1 year after operation. METHODS: Na2 ethylenediamine tetraacetic acid and CaCI2 were infused at constant rates in six patients operated on for parathyroid adenoma and six healthy individuals. Serum levels of intact PTH and ionized calcium were determined during the infusions. RESULTS: No significant differences between the two groups were found in baseline levels of serum ionized calcium and PTH. Furthermore, no significant differences between patients and control subjects were found in the maximum serum PTH levels during the hypocalcemic infusion of ethylenediamine tetraacetic acid or in the minimum serum PTH levels during the calcium infusion. In contrast, the set point (the calcium concentration required for half-maximal inhibition of PTH secretion) was significantly lower in the patients (1.20 +/- 0.01 mmol/L) compared with control subjects (1.22 +/- 0.01 mmol/L; p < 0.05). CONCLUSIONS: We conclude that the elevation of set point in patients with parathyroid adenoma is corrected by successful operation. This suggests a monoclonal origin of parathyroid adenomas. PMID- 8506525 TI - Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. AB - BACKGROUND: The polysplenia syndrome is the most common extrahepatic anomaly found in association with extrahepatic biliary atresia. This subgroup may have a different cause and a worse prognosis than do infants with biliary atresia alone, and this hypothesis has been tested by analyzing the King's College Hospital series. METHODS: The case records of 308 infants treated between 1975 and 1991 for biliary atresia were examined for extrahepatic anomalies. RESULTS: Twenty three (7.5%) infants had polysplenia and biliary atresia. There were also four infants with other types of splenic malformation: two with double spleen and two with asplenia. The presence of other anomalies such as situs inversus and portal vein anomalies in all the categories of splenic malformation suggests that they formed part of a larger association for which we now propose the term biliary atresia splenic malformation (BASM) syndrome. There was no difference in age at presentation and in biochemical test results of liver function before operation between infants with BASM and those with biliary atresia alone. Four (15%) infants with BASM were born to mothers with diabetes (three insulin dependent and one with gestational diabetes treated by diet alone). There were no other cases of maternal diabetes in the series as a whole. Actuarial "survival" (death or transplant) of infants with BASM after initial corrective operation was worse than that in a control group without anatomic anomalies (p < 0.05). CONCLUSIONS: BASM syndrome appears to be a distinct subgroup in infants with biliary atresia. This subgroup may have a different cause and tends to have a worse prognosis than do control subjects. Whether this is caused by the presence of the other anomalies (e.g., cardiovascular anomalies), which are in themselves detrimental, is unclear. PMID- 8506524 TI - Incidence, structure, and function of enlarged parathyroid glands discovered accidentally during thyroid surgery. AB - BACKGROUND: Operation on rare patients with mainly a severe renal stone disease and considerably elevated urinary calcium excretion has substantiated the association of parathyroid gland abnormalities with normocalcemia. This study examines incidence, structure, and functional characteristics of enlarged parathyroid glands of patients with normocalcemia scheduled for thyroid surgery. METHODS: Eleven enlarged parathyroid glands weighing 110 to 1000 mg were discovered in 9 (1.5%) of 594 patients with normocalcemia undergoing thyroid operation. The preoperative total serum calcium concentration was 2.30 to 2.52 mmol/L and less than 2.38 mmol/L in four of the nine patients. Intact serum parathyroid hormone and alkaline phosphatase levels were elevated in only one individual, and all patients showed normal serum creatinine values. RESULTS: All but three of the 11 enlarged parathyroid glands exhibited microscopic abnormality on routine histopathologic examination, including staining for cytoplasmic fat with oil red 0. Immunohistochemical staining with a monoclonal antibody recognizing the functionally important calcium receptor of the parathyroid cell surface and analysis of the calcium-regulated cytoplasmic Ca2+ concentration of dispersed parathyroid cells substantiated that only a single gland of 130 mg had no discernible functional abnormality. CONCLUSIONS: The findings underline the diagnostic difficulties of parathyroid histopathology and support the presence of disturbed parathyroid hormone secretion even in normocalcemic patients with enlarged parathyroid glands. The functional derangement of these glands substantiates the indication for their surgical excision even in patients exhibiting midnormal serum calcium concentrations, although their possible contribution to the development of a clinically overt hyperparathyroidism can only be speculated. PMID- 8506526 TI - Effects of triiodothyronine on canine hepatic ischemia caused by Pringle's maneuver. AB - BACKGROUND: A significant reduction in the serum concentration of triiodothyronine is frequently observed in surgical stress and may influence the severity and prognosis of the underlying disease. METHODS: Alterations of thyroid hormone levels and effects of triiodothyronine were evaluated in the shock state after Pringle's maneuver for 60 minutes in dogs. Triiodothyronine (1 micrograms/kg/hr) was infused intravenously for 3 hours after declamping in the triiodothyronine-treated group. The effect of triiodothyronine on hepatic mitochondrial function was investigated by measuring the arterial ketone body ratio (AKBR). RESULTS: In the control group (n = 6) the low triiodothyronine syndrome was observed and progressive deterioration of AKBR and standard liver functions represented by aspartate aminotransferase, glutamic-pyruvic transaminase, and lactic dehydrogenase were noted after declamping. All dogs went into shock and died within 24 hours. By contrast, in the triiodothyronine-treated group (n = 6), hemodynamics were stabilized and standard liver functions were maintained favorably (p < 0.01). AKBR was fully restored to the preischemic liver within 30 minutes after declamping, with a decrease in serum lactate levels (p < 0.05). All dogs survived at least 7 days after operation (p < 0.01). CONCLUSIONS: These results indicate that triiodothyronine has beneficial effects on cytoprotection, hemodynamics, and hepatic energy metabolism in the ischemic liver injury. Furthermore, it improves survival in the shock state after Pringle's maneuver. PMID- 8506527 TI - Inhibition of tumor cell adhesion to lymph nodes by laminin-related peptide and neuraminidase. AB - BACKGROUND: Adhesion to lymph nodes, rather than growth stimulation, accounted for preferential colonization of lymph nodes by a metastatic B16 melanoma. We investigated these adhesive interactions. METHODS: Four classes of molecules were tested for inhibition of melanoma adhesion to cryostat sections of lymph node. RESULTS: Calcium chelators ethylenediaminetetraacetic acid and ethyleneglycol-bis (beta-aminoethylether)-N,N,N',N'-tetra ace tic acid completely inhibited adhesion (50% adhesion, half-maximal inhibition, at 1 to 3 mmol/L). Cytochalasin B, which impairs contractile microfilaments, inhibited adhesion (60% adhesion at .001 mmol/L, 28% at .01 mmol/L). Colchicine, which disaggregates microtubules, had a similar effect (20% at .01 mmol/L, lowest dose tested). Trypsin slightly increased adhesion (125% adhesion at 10 micrograms/ml). Neuraminidase, which removed sialic acid residues, inhibited it (50% adhesion at 5 micrograms/ml). Gly arg-gly-asp-ser, a peptide with a cell binding sequence of fibronectin, did not consistently inhibit adhesion (69% adhesion at 0.1 mg/ml, 83% adhesion at 1 mg/ml) or substantially differ from gly-arg-gly-glu-ser-pro (59% adhesion at 0.1 mg/ml, 90% adhesion at 1 mg/ml). In contrast, a peptide with a cell binding region of laminin (tyr-ile-gly-ser-arg) inhibited adhesion (50% adhesion at .05 mg/ml). CONCLUSIONS: Tumor cell-lymph node adhesion is a calcium-dependent process, requiring a functional cytoskeleton, that is mediated by both sialic acid moieties and trypsin-resistant, laminin-related, adhesion molecules. PMID- 8506528 TI - Shear stress modulates the proliferation rate, protein synthesis, and mitogenic activity of arterial smooth muscle cells. AB - BACKGROUND: The aim of this study was to determine the correlation between hemodynamic forces and proliferation of smooth muscle cells (SMC). METHODS: Bovine arterial SMC were seeded in a fibronectin-coated polystyrene cylinder at 5 x 10(5) cells/tube and allowed to reach confluence and to adhere for 48 hours. The experimental groups were subjected to a laminar flow of 150 ml/min (9 dyne/cm2), 100 ml/min (6 dyne/cm2), and 50 ml/min (3 dyne/cm2) for 24 hours. The control group was subjected to similar incubation conditions without flow. The cells in the experiments remained attached and viable. All experiments were performed in triplicate or more. RESULTS: Shear stress significantly reduced (p < 0.001) the 24-hour incorporation of tritiated thymidine and cell proliferation. This effect was proportional to the level of shear stress and was still evident 24 hours after flow cessation. Results of flow cytometry confirmed a lower percentage of SMC in S phase with increasing shear stress. Synthesis of cell associated proteins was increased twofold (p < 0.01) in SMC subjected to laminar flow. SMC subjected to shear stress released a higher quantity of mitogens, including a platelet-derived growth factor (PDGF)-like substance as detected by immunologic testing. Fifty percent volume per volume conditioned serum-free medium from SMC subjected to shear stress increased threefold the tritiated thymidine uptake in PDGF receptor-bearing Swiss 3T3 cells as compared with conditioned serum-free medium from control SMC not subjected to shear stress and twelvefold as compared with standard control. The release of mitogens was proportional to the level of shear stress and was still evident 24 hours after flow cessation. The mitogenic activity was partially reduced (30%, p < 0.01) by an excess of monospecific anti-PDGF antibody. CONCLUSIONS: We conclude that (1) increasing shear stress inhibits SMC proliferation and stimulates the synthesis of cell-associated proteins and the release of mitogens and (2) decreasing shear stress facilitates proliferation of SMC. Thus, in situations of arterial flow separation, the increased release of mitogens from SMC subjected to high shear stress and the increased proliferation rate and susceptibility to mitogens of SMC subjected to very low shear stress may generate a critical condition that predisposes to the development of atherosclerosis with early plaque formation in regions of low-flow shear stress. PMID- 8506529 TI - Impaired endothelial prostacyclin production of the canine vein graft in a poor distal runoff limb. AB - BACKGROUND: Because blood flow modulates endothelial prostacyclin production, the extent of this production in autologous vein grafts implanted in poor distal runoff limbs needed to be examined. METHODS: Endothelial prostacyclin production in canine autologous vein grafts was measured in poor distal runoff limbs (poor runoff group) and compared with findings in normal runoff limbs (control group). Vein grafts were perfused in a closed circuit at 3 days and 1, 2, 3, and 4 weeks after implantation; after perfusion for the first 30 minutes in a steady flow (basal prostacyclin production), the grafts were exposed to arachidonic acid (stimulated prostacyclin production) for the following 30 minutes. Prostacyclin, as the metabolite 6-keto-PGF1 alpha, was radioimmunoassayed. RESULTS: Basal and stimulated prostacyclin production increased in both groups during a period of time after implantation. At 2 weeks when endothelialization was complete, prostacyclin production in the poor runoff group was impaired, compared with the findings in the control group, and this difference increased with time. At 4 weeks the stimulated prostacyclin production was 18.91 +/- 4.03 ng/cm2 in the control group and 11.60 +/- 1.67 ng/cm2 in the poor runoff group (p < 0.05). CONCLUSIONS: We propose that the impaired capacity of the vein graft to produce prostacyclin in a poor distal runoff may lead to loss of graft patency in reconstructed arteries. PMID- 8506530 TI - Body smuggling of illicit drugs: two cases requiring surgical intervention. AB - The smuggling of illicit drugs by concealing them within the human body has become a widespread practice. Those individuals who transport packaged drugs are commonly known as "body packers" or "mules". "Body stuffers," on the other hand, are individuals who emergently place the contraband in a body orifice when they sense apprehension is imminent. In the latter instance, the drugs are not well packaged for transportation by human "consumption," hence the high risk for leakage. These individuals require prompt surgical attention under two circumstances: when they are found to suffer from drug overdosage caused by inadvertent leakage or when obstruction in the body is caused by the drug-laden bags. Two such cases are reported. The first patient presented with acute drug overdose and required an emergency laparotomy. The second patient presented with pyloric obstruction and was treated by endoscopic removal of the bag. One must be aware that these patients are walking time bombs, carrying drugs that may be well packed but have the potential to deliver a lethal dose without warning. Knowledge of the type of drug and type of packaging are essential in managing these patients. The overall plan should be close observation, careful monitoring, conservative therapy, and expectant rapid surgical intervention as needed. PMID- 8506531 TI - Primary adenocarcinoma in an ileostomy: a late complication of surgery for ulcerative colitis. AB - In the 1950s the treatment of ulcerative colitis was revolutionized by Brooke by way of a colectomy combined with an eversion ileostomy. This procedure is known to be associated with a number of complications that include skin excoriation, stenosis, intestinal obstruction, retraction or prolapse of the stoma, abscess and fistula formation, and ileitis. However, adenocarcinoma arising in the abnormally placed small intestinal mucosa 20 years or more after the initial operation is being increasingly recognized and reported. This article describes one such case and includes an extensive review of the current world literature on the subject of adenocarcinoma arising as a late complication of operation for ulcerative colitis. PMID- 8506532 TI - Coexisting hyperthyroidism and primary hyperparathyroidism. AB - The simultaneous occurrence of hyperthyroidism and primary hyperparathyroidism is rare in the absence of previous neck irradiation. We report two cases from our institution. Hypercalcemia secondary to hyperthyroidism is common and may obfuscate the diagnosis of concomitant primary hyperparathyroidism. Therefore the continued presence of hypercalcemia in a patient with successfully treated hyperthyroidism should lead the physician to search for primary hyperparathyroidism. Treatment of these concomitant disease processes consists of combined thyroidectomy and parathyroidectomy. PMID- 8506533 TI - Postoperative ascitic leak after colostomy. PMID- 8506534 TI - Retroperitoneal laparostomy. PMID- 8506535 TI - Nutritional status after Roux-en-Y gastric bypass surgery. PMID- 8506536 TI - Do we need a concept of disease? AB - The terms "health", "disease" and "illness" are frequently used in clinical medicine. This has misled philosophers into believing that these concepts are important for clinical thinking and decision making. For instance, it is held that decisions about whether or not to treat someone or whether to relieve someone of moral responsibility depend on whether the person has a disease. In this paper it is argued that the crucial role of the 'disease' concept is illusory. The health/disease distinction is irrelevant for most decisions and represents a conceptual straightjacket. Sophisticated and mature clinical decision making requires that we free ourselves from the concept of disease. PMID- 8506537 TI - On the relevance and importance of the notion of disease. AB - This paper constitutes a defence of the basic philosophical enterprise of characterising concepts such as 'disease' and 'health', as well as other medical concepts. I argue that these concepts play important roles, not only in medical, but also in other scientific and social contexts. In particular, medical decisions about health and diseasehood have important ethical, social and economic consequences. The role played is, however, not always a rational one. But the greater is the need for a reconstruction of this network of concepts for the purpose of efficient and rational communication. PMID- 8506538 TI - What's so special about medicine? AB - Health care has increasingly come to be understood as a commodity. The ethical implications of such an understanding are significant. The author argues that health care is not a commodity because health care (1) is non-proprietary, (2) serves the needs of persons who, as patients, are uniquely vulnerable, (3) essentially involves a special human relationship which ought not be bought or sold, (4) helps to define what is meant by 'necessity' and cannot be considered a commodity when subjected to rigorous conceptual analysis. The Oslerian conception that medicine is a calling and not a business ought to be reaffirmed by both the profession and the public. Such a conception would have significant ramifications for patient care and health care policy. PMID- 8506539 TI - Medical diagnostic reasoning: epistemological modeling as a strategy for design of computer-based consultation programs. AB - The complexity of cognitive emulation of human diagnostic reasoning is the major challenge in the implementation of computer-based programs for diagnostic advice in medicine. We here present an epistemological model of diagnosis with the ultimate goal of defining a high-level language for cognitive and computational primitives. The diagnostic task proceeds through three different phases: hypotheses generation, hypotheses testing and hypotheses closure. Hypotheses generation has the inferential form of abduction (from findings to hypotheses) constrained under the criterion of plausibility. Hypotheses testing is achieved by a deductive inference (from generated hypotheses to expected findings), followed by an eliminative induction, constrained under the criterion of covering, which matches expected findings against patient's findings to select the best explanation. Hypotheses closure is a deductive-inductive type of inference very similar to the inferences operating in hypotheses testing. In this case induction matches the consequences of the generated hypotheses against the patient's characteristics or preferences under the criterion of utility. By using the language exploited in this epistemological model, it is possible to describe the cognitive tasks underlying the most influential knowledge-based diagnostic systems. PMID- 8506540 TI - What is an expert? AB - Experts play an important role in society, but there has been little investigation about the nature of expertise. I argue that there are two kinds of experts: those whose expertise is a function of what they know (epistemic expertise), or what they do (performative expertise). Epistemic expertise is the capacity to provide strong justifications for a range of propositions in a domain, while performative expertise is the capacity to perform a skill well according to the rules and virtues of a practice. Both epistemic and performative experts may legitimately disagree with one another, and the two senses are conceptually and logically distinct. PMID- 8506541 TI - [Occipital dysplasia in a Pomeranian dog]. AB - Occipital dysplasia, a congenital malformation of the foramen magnum, was diagnosed in a 4-year-old Pomeranian dog. The diagnosis was made by clinical and radiographic findings. Caudal displacement of the cerebellum and hydrocephalus were diagnosed postmortem, using a radiographic contrast study of the subarachnoid space. PMID- 8506542 TI - [Pilot study of the Deosan-RMTK (rapid mastitis test kit), a diagnostic test for the detection of cows with high cell count]. AB - The Deosan-Rapid Mastitis Test Kit (RMTK) was evaluated in 226 lactating dairy cows on 6 farms. The Fossomatic method was used as reference standard for somatic cell counts in cows milk. The RMTK test-principle regards the reaction of the enzyme catalase released from cells in milk with the H2O2 in the RMTK-reagent. For the threshold cell count values of 250,000, 400,000 and 800,000/ml the following 95% confidence intervals were found: sensitivity 0.60-0.99 specificity 0.42-0.83, predictive value positive 0.22-0.46, predictive value negative 0.84 0.99 and kappa-value 0.14-0.52. Because this test will be most useful when the positive predictive value would be high, it is concluded that the RMTK in this study population was not an adequate tool for the detection of cows with somatic cell counts over 250,000/ml milk. PMID- 8506543 TI - [Udder infections with coagulase-negative staphylococci in freshly calved heifers]. AB - To determine the prevalence of udder infections in fresh calved heifers all quarters of 98 heifers on eleven commercial farms were sampled weekly during the first eight weeks of lactation. The samples during the first four weeks of this period were used for bacteriological examination and in all samples a somatic cell count was made. The prevalence of S. aureus after calving in these heifers was 12.5%. Coagulase-negative staphylococci (CNS) were isolated from half of the heifers. The predominant coagulase-negative staphylococcus species were S. xylosis and S. hyicus. The CNS, with exception of S. hyicus, had a very small effect on the cell count. PMID- 8506544 TI - [The role of ultrasonography in the diagnosis of liver diseases in dogs]. AB - Ultrasonography is a non-invasive technique, which can be useful in the diagnosis of liver diseases. Three cases are presented and the possibilities and limitations of the technique are discussed. PMID- 8506545 TI - [Order or chaos?]. PMID- 8506546 TI - [Test quality standards of milk]. PMID- 8506547 TI - Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels. AB - BACKGROUND AND PURPOSE: The clinical pattern of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese are different from those in Caucasians. Pathological data from autopsy studies are lacking. METHODS: The intracranial and extracranial arteries supplying the brains of 114 consecutive Chinese patients undergoing autopsy in a regional general hospital were examined by computer-assisted morphometric analysis under a microscope as well as by macroscopic grading for atherosclerotic narrowing. The severity was correlated with various atherosclerosis-related factors. RESULTS: Atherosclerosis of the intracranial cerebral vessels was more severe than that of the extracranial vessels. The distal branches of the intracranial vessels were also commonly involved. Hypertension and diabetes mellitus were identified as factors associated only with intracranial atherosclerosis (p < 0.001), whereas ischemic heart disease was associated with atherosclerosis in both the intracranial (p < 0.001) and extracranial (p = 0.012) vessels. Smoking was associated with narrowing of the extracranial vessels only (p = 0.0054). CONCLUSIONS: Compared with figures from Caucasian and Japanese populations, the extent of intracranial atherosclerosis is much more severe in Hong Kong Chinese, whereas atherosclerotic narrowing of the extracranial carotid artery is less severe in Hong Kong Chinese than in Caucasians. PMID- 8506548 TI - Geographic variation in the incidence of nonfatal stroke in Finland. Are the observed differences real? FINMONICA Stroke Register Study Group. AB - BACKGROUND AND PURPOSE: We sought to find an explanation for the geographical variation in the incidence of nonfatal stroke detected in the FINMONICA stroke register during the period 1983-1985. METHODS: Two separate investigations were made. In the first, a sample of approximately 100 nonfatal events drawn from each of the three monitoring areas (North Karelia, Kuopio, and Turku/Loimaa) participating in FINMONICA was recoded by an independent coder. In the second, 29 nonfatal events from Kuopio and 29 from North Karelia were recorded by the neurologist of the other area. Kappa coefficients (kappa) were calculated to measure the proportion of agreement beyond chance among the different coders. RESULTS: A good level of agreement with the independent coder was found for each of the three areas; it was best for the cases from Turku/Loimaa (kappa = 0.896), followed by Kuopio (kappa = 0.792) and North Karelia (kappa = 0.616). In the second part of the investigation, agreement was higher for the stroke cases originating from Kuopio (kappa = 0.861) than for those from North Karelia (kappa = 0.563). In the latter there was discrepancy in the classification of the cases originally classified as no stroke. CONCLUSIONS: The results from the first part of the investigation suggest that the lower incidence of nonfatal stroke in Turku/Loimaa was real, confirming findings in previous studies. Differences in data entry, rather than in the interpretation of signs and symptoms of stroke, were the main cause of disagreement in the second part of the investigation, where the disagreement primarily concerned the cases classified as no stroke in North Karelia. The results also indicate that the different proportions of patients submitted to computerized brain tomography conceivably account for a good part of the difference in the incidence rates of nonfatal stroke between Kuopio and North Karelia. PMID- 8506549 TI - A prospective study of stroke in young adults in Cantabria, Spain. AB - BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence, type, and prognosis of stroke in young adults in Cantabria, Spain. METHODS: We investigated prospectively all patients aged 50 years or below who were admitted with the diagnosis of a stroke to the University Hospital "Marques de Valdecilla" from April 1, 1986, to March 31, 1988. This is the main hospital of the region to which all patients with neurological problems are referred. These patients underwent a complete clinical and laboratory assessment for stroke and had 1-year mean follow-up. RESULTS: The total series included 81 patients. The annual age specific crude incidence rates of stroke were 17.3 and 10.4 per 100,000 for males and females, respectively. Twenty-four patients (30%) were diagnosed as having nonembolic cerebral infarction, 14 (17%) embolic cerebral infarction, 20 (25%) subarachnoid hemorrhage, 22 (27%) spontaneous cerebral hemorrhage, and one case (1%) cerebral venous thrombosis. Eighteen patients (22%) died within 30 days of the cerebrovascular event, and two others died during the follow-up period. Seventy-nine percent of the survivors recovered and were completely self sufficient. CONCLUSIONS: The incidence of stroke in the young found in Cantabria is comparable with that in previous studies. The initial hospital mortality was not negligible, but the prognosis among the survivors was favorable. PMID- 8506550 TI - Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. AB - BACKGROUND AND PURPOSE: There have been relatively few community-based studies of long-term prognosis after acute stroke. This study aimed to provide precise estimates of the absolute and relative risks of dying in an unselected cohort of patients with a first-ever stroke. METHODS: Six hundred seventy-five patients were registered by a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed up for up to 6.5 years. Their relative risk of death was calculated using age- and sex-specific mortality rates for Oxfordshire. RESULTS: During the first 30 days, 129 (19%) patients died. Patients who survived at least 30 days after a first-ever stroke thereafter had an average annual risk of death of 9.1%, 2.3-fold the risk in people from the general population. Although the absolute (about 15%) and relative (about threefold) risks of death were highest in these 30-day survivors over the first year after the stroke, they were at increased risk of dying over the next few years (range of relative risk for individual years, 1.1-2.9). Predictably, older patients had a worse absolute survival but, relative to the general population, stroke also increased the relative risk of dying in younger patients. During the first 30 days stroke accounts for most deaths; after this time nonstroke cardiovascular disease becomes increasingly important and is the most common cause of death after the first year. CONCLUSIONS: These data highlight the importance of long term secondary prevention of vascular events in stroke patients, targeted as much at the cardiovascular as at the cerebrovascular circulation. PMID- 8506551 TI - Coagulation-fibrinolysis system in poststroke patients receiving antiplatelet medication. AB - BACKGROUND AND PURPOSE: We studied the activities of the coagulation-fibrinolysis system in the chronic stage of poststroke patients and the effect of antiplatelet medication on the system. METHODS: We determined fibrinogen, antithrombin III, thrombin-antithrombin III complex, tissue plasminogen activator antigen, plasminogen activator inhibitor-1, plasmin-alpha 2 plasmin inhibitor complex, and D-dimer in plasma from 153 poststroke patients in the chronic phase (ie, 33 patients not receiving antiplatelet medication, 78 patients receiving 200 mg/d ticlopidine, and 42 patients receiving 40 mg/d aspirin), and compared the results in control subjects and among the treatment groups. RESULTS: The concentrations of fibrinogen, thrombin-antithrombin III complex, antithrombin III, plasmin-alpha 2 plasmin inhibitor complex, and tissue plasminogen activator were slightly but significantly increased in all treatment groups compared with control subjects (P < .01) but did not differ among the treatment groups. The plasminogen activator inhibitor-1 levels were significantly elevated in patients not receiving antiplatelet medication compared with control subjects (P < .01), whereas they were in the normal range and significantly lower in patients receiving ticlopidine or aspirin than in patients not receiving antiplatelet medication (P < .01). The plasminogen activator inhibitor-1 levels were significantly lower in patients whose platelet aggregation was inhibited by antiplatelet medication than in patients with uninhibited platelet aggregability (P < .05). CONCLUSIONS: These findings suggest that coagulation-fibrinolysis markers are mildly increased in poststroke patients in the chronic phase and that antiplatelet medication is effective in reducing the elevated plasminogen activator inhibitor-1 levels. PMID- 8506552 TI - Amount of blood on computed tomography as an independent predictor after aneurysm rupture. AB - BACKGROUND AND PURPOSE: After admission to the hospital of patients with aneurysmal subarachnoid hemorrhage, we assessed the predictive value of the extent of the hemorrhage on computed tomography in addition to that of clinical grading scales for poor outcome, infarction, and rebleeding. METHODS: We studied 471 consecutive patients with aneurysmal subarachnoid hemorrhage and used logistic regression with step-wise forward selection of variables. RESULTS: On admission, poor outcome was predicted by a low Glasgow Coma Scale score (odds ratio, 0.8; 95% confidence interval, 0.7-0.9); treatment with fluid restriction (2.5; 1.6-4.0); age over 52 (2.6; 1.7-3.9); loss of consciousness at ictus (1.7; 1.1-2.6); or a large amount of subarachnoid blood (2.0; 1.3-3.1). Delayed infarction was predicted by a large amount of subarachnoid blood (1.8; 1.2-2.6) or treatment with tranexamic acid (1.6; 1.1-2.4). Rebleeding was predicted by treatment with tranexamic acid (0.4; 0.3-0.7; protective effect); age over 52 (1.9; 1.2-3.0); loss of consciousness at ictus (1.7; 1.1-2.7); or admission to a neurosurgery service (0.6; 0.3-0.9; protective effect). Comparison of the observed and predicted outcome events showed that inclusion of the amount of subarachnoid blood into a predictive model added little to the prediction of poor outcome in general, but much to the prediction of delayed cerebral ischemia. CONCLUSIONS: The total amount of subarachnoid blood on the initial computed tomogram has independent predictive power for the occurrence of delayed cerebral ischemia. PMID- 8506553 TI - Noninvasive detection of vertebral artery dissection. AB - BACKGROUND AND PURPOSE: We sought to identify the use of duplex and transcranial Doppler sonography in the noninvasive diagnosis of vertebral dissection. METHODS: Ten patients with a diagnosis of symptomatic vertebral artery dissection confirmed by cerebral angiography were retrospectively analyzed. RESULTS: Computed tomographic scanning and magnetic resonance imaging together delineated lateral medullary or cerebellar infarcts in 7 patients. Angiography documented a total of 21 vertebral artery lesions (16 stenoses and 5 occlusions), with 7 of 10 patients having multiple sites of vertebral artery dissection. Vertebral Doppler was abnormal in 8 of the 10 patients. A high resistance signal in the relevant vertebral artery was found in 6 patients, no flow in a well-imaged vertebral artery in 1, and bilateral retrograde vertebral artery flow in 1 patient. Transcranial Doppler was abnormal in only 2 patients, with reduced pulsatility index in 1 and high resistance vertebral signal in another. A hyperintense intramural signal of the affected vertebral artery by magnetic resonance imaging was documented in 1 patient in whom Doppler sonography was nondiagnostic. CONCLUSIONS: Vertebral artery dissection can be detected and monitored by noninvasive vertebral Doppler and magnetic resonance imaging in the setting of a clinically suggestive presentation. PMID- 8506554 TI - Thromboxane antagonism in experimental canine carotid artery thrombosis. AB - BACKGROUND AND PURPOSE: The two objectives of this study were to assess the potential of BAY U 3405 to prevent arterial thrombosis in response to vessel wall injury and to determine the ability of BAY U 3405 to prevent thrombotic reocclusion after thrombolysis with anisoylated plasminogen streptokinase activator complex. METHODS: Dogs were instrumented with a carotid flow probe, stimulating electrode, and a stenosis. Current (150 microA) was applied to the intimal surface of the right carotid artery, and time to occlusive thrombus formation was noted. BAY U 3405 was administered, and the procedure for thrombus formation was repeated for the left carotid artery. RESULTS: BAY U 3405 administration prevented occlusive arterial thrombosis formation. Ex vivo platelet aggregation was inhibited, bleeding time increased, and thrombus weight reduced after BAY U 3405 treatment. In a second group, thrombi were formed initially in both carotid arteries, BAY U 3405 was administered as before, and anisoylated plasminogen streptokinase activator complex was infused in the right carotid artery proximal to the occlusive thrombus. BAY U 3405 did not alter the incidence of rethrombosis compared with the lytic agent alone. CONCLUSIONS: BAY U 3405 prevented primary arterial thrombosis, corresponding to inhibition of platelet aggregation, and increased bleeding times. BAY U 3405, however, did not prevent rethrombosis after successful thrombolysis with anisoylated plasminogen streptokinase activator complex, despite the fact that platelet reactivity was inhibited. The data are consistent with the concept that the residual thrombus represents a more effective thrombogenic stimulus as compared with arterial wall injury alone and that the mechanisms associated with primary versus secondary thrombus formation may require separate therapeutic approaches. PMID- 8506555 TI - Oxyhemoglobin-induced cytotoxicity and arachidonic acid release in cultured bovine endothelial cells. AB - BACKGROUND AND PURPOSE: An impairment of endothelial function is associated with vasospasm after subarachnoid hemorrhage. Oxyhemoglobin is considered to be a critical trigger in the pathogenesis of vasospasm. The present studies examined the direct effects of oxyhemoglobin on cultured endothelial cells from bovine carotid artery. METHODS: Confluent endothelial cells were treated with oxyhemoglobin, and the following were studied: 1) cell morphology, 2) cell density, and 3) the release of radiolabel from [3H]arachidonic acid-treated cells. RESULTS: Endothelial cells exposed to oxyhemoglobin exhibited detachment vacuoles, and cell density was significantly decreased in time- and dose dependent manners. Superoxide dismutase, a free radical scavenger, provided partial protection against the cytotoxic effects of oxyhemoglobin. The release of radiolabel from [3H]arachidonic acid-treated cells was increased by oxyhemoglobin in time- and dose-dependent manners. Treatment with an inhibitor of phospholipase A2 or a calcium chelator inhibited the effects of oxyhemoglobin on arachidonic acid release and cellular viability. CONCLUSIONS: Oxyhemoglobin exerts a direct cytotoxic effect on cultured endothelial cells, and this effect is associated with increased release from [3H]arachidonic acid-labeled cells. Phospholipase A2 and free radicals appear to participate in the pathogenesis of endothelial cell damage. Oxyhemoglobin-induced compromise of endothelial cells may contribute to cerebrovascular pathology. PMID- 8506556 TI - Tissue factor contributes to microvascular defects after focal cerebral ischemia. AB - BACKGROUND AND PURPOSE: Microvascular perfusion defects occur after occlusion and reperfusion of the middle cerebral artery in examples of focal cerebral ischemia. In addition to cellular (eg, polymorphonuclear leukocyte) contributors to the focal "no-reflow" phenomenon, activation of coagulation may also play a role. We have tested a potential role of tissue factor-mediated coagulation in the microvascular perfusion defects seen after focal cerebral ischemia-reperfusion in a baboon model of reversible middle cerebral artery occlusion with the murine anti-tissue factor monoclonal antibody TF9-6B4. Tissue factor is the principal resident procoagulant substance in cerebral tissues and has a distinct perivascular distribution. METHODS: Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion was quantified by computerized video imaging of carbon-tracer perfused tissues. Animals were randomized to receive intravenous TF9-6B4 (10 mg/kg) 10 minutes before middle cerebral artery occlusion (n = 6) or no treatment (n = 6) in an open study. RESULTS: In the control animals, a significant decrease in patency was confirmed in microvessels less than 30 microns in diameter. Infusion of TF9 6B4 before middle cerebral artery occlusion produced a stable maximal level of circulating antibody within 10 minutes, which lasted the duration of ischemia and reperfusion. An increase in reflow in microvessels of all size classes occurred after TF9-6B4 infusion, which was significant in those 7.5 to 30 microns (P = .038) and 30 to 50 microns (P = .013) in diameter. CONCLUSIONS: These results indicate that tissue factor-mediated events may also contribute to no-reflow in noncapillary microvessels after focal cerebral ischemia. PMID- 8506557 TI - Modification of hypoxia-induced injury in cultured rat astrocytes by high levels of glucose. AB - BACKGROUND AND PURPOSE: Preexisting hyperglycemia exacerbates central nervous system injury after transient global and focal cerebral ischemia. Increased anaerobic metabolism with resultant lactic acidosis has been shown to cause the hyperglycemic, neuronal injury. The contribution of astrocytes in producing lactic acidosis under hyperglycemic/ischemic conditions is unclear, whereas the protective role of astrocytes in ischemic-induced neuronal injury has been documented. The ability of astrocytes to maintain energy status and ion homeostasis under hyperglycemic conditions could ultimately reduce neuronal injury. Therefore, we determined the effects of increased glucose concentrations on glucose utilization, lactate production, extracellular pH, and adenosine triphosphate concentrations in hypoxia-treated astrocyte cultures. METHODS: Primary astrocytes were prepared from neonatal rat cerebral cortices. After 35 days in vitro, cultures were incubated with 0-60 mmol/L glucose and subjected to hypoxic conditions at 95% N2/5% CO2 for 24 hours. In addition, under high-glucose conditions (30 mmol/L), astrocytes were exposed to up to 72 hours of hypoxia. Determination of lactate dehydrogenase efflux, adenosine triphosphate concentrations, and extracellular lactate concentrations defined astrocyte status. Equiosmolar levels of mannitol were added in place of high glucose concentrations to distinguish hyperosmotic effect. RESULTS: When physiological concentrations of glucose (7.5 mmol/L) or lower concentrations were used, significant cell damage occurred with 24 hours of hypoxia, as determined by increased efflux of lactate dehydrogenase and loss of cell protein. When higher glucose concentrations (15-60 mmol/L) were used, efflux of lactate dehydrogenase was similar to that observed in normoxic cultures, despite an increased utilization of glucose. Lactate concentrations in the media at low or normal glucose concentrations exceeded normoxic levels, but higher glucose concentrations (15-30 mmol/L) failed to increase lactate levels further. Values of adenosine triphosphate for hypoxic astrocytes treated with high glucose concentrations were significantly higher than those of astrocytes with zero or low glucose levels. In cultures exposed to hypoxia and high glucose levels (30 mmol/L), no cellular injury was observed before 48 hours of hypoxia. Lactate concentrations in the media increased during the first 24 hours of hypoxia and reached steady state. The pH of the media decreased to 6.4 after 24 hours and 5.5 at 48 hours. The latter pH was concomitant with a marked increase in extracellular lactate dehydrogenase activity. Hyperosmotic mannitol failed to protect cultured astrocytes against hypoxia. CONCLUSIONS: Hypoxic injury to mature astrocytes was reduced by the presence of 15-60 mmol/L glucose in the medium during 24-30 hours of hypoxia. Injury occurred when the pH of the medium was < 5.5. This protection was not afforded by the hyperosmotic effect of high glucose concentrations, nor was the hypoxic injury at later time periods with 30 mmol/L glucose mediated solely by lactate accumulation. PMID- 8506558 TI - Failure of MK-801 to reduce infarct volume in thrombotic middle cerebral artery occlusion in rats. AB - BACKGROUND AND PURPOSE: We examined the effects of the noncompetitive N-methyl-D aspartate receptor antagonist MK-801 using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion under conditions of carefully controlled head temperature. METHODS: Male Sprague-Dawley rats were treated with 1 mg/kg of MK-801 or saline before the induction of ischemia. An argon laser activated dye laser (562 nm) was used to cause thrombotic distal middle cerebral artery occlusion. In experiments 1 and 2, the single laser beam (20 mW) was separated into three beams. Each beam was positioned onto the distal middle cerebral artery at three sites along the vessel. The photosensitizing dye rose bengal (20 mg/kg) was administered intravenously over 2 minutes; the three points were then irradiated for 3 minutes. In experiment 3, higher power of the laser (three separate irradiations using a single beam of 20 mW) was used. The ipsilateral common carotid artery was occluded permanently, and the contralateral carotid artery was occluded for 60 minutes. Head temperature was controlled at 36 degrees C in experiment 1 and not controlled in experiments 2 and 3. Three days after the ischemic insult, brains were perfusion-fixed and infarct volumes were determined. RESULTS: Head temperature was mildly hypothermic (34-35 degrees C before ischemia, with a further decrease of 1-2 degrees C during the initial 60 minutes of ischemia) in experiment 2. However, no differences were observed in head temperature between the MK-801-treated and control groups. Cortical infarct volume in experiment 1 was 89 +/- 29 mm3 (mean +/- SD) in the treated group, which was not different from the control value of 84 +/- 40 mm3. Infarct volumes were smaller (58 +/- 35 mm3 and 54 +/- 14 mm3) in the control groups of experiments 2 and 3, respectively. However, MK-801 also failed to reduce infarct volumes in experiments 2 and 3. CONCLUSIONS: MK-801 is not effective in this stroke model of focal thrombotic infarction under conditions of either controlled (normothermic) or uncontrolled (mildly hypothermic) head temperature. PMID- 8506559 TI - The effect of a new calcium antagonist, TA3090 (clentiazem), on experimental transient focal cerebral ischemia in cats. AB - BACKGROUND AND PURPOSE: TA3090 (Clentiazem) has been shown to have cerebrovascular protective properties in three experimental studies. An in vivo investigation was undertaken to determine its effects on pial arteries and cerebral blood flow and its therapeutic value in transient focal cerebral ischemia. METHODS: This experiment was divided into two protocols. In the first, 200 or 400 micrograms/kg per hour TA3090 was administered continuously for 3 hours in cats without ischemic insult (n = 6 for each group). The effects on pial arteries and cerebral blood flow were estimated. In the second protocol, 400 micrograms/kg per hour TA3090 (treated group, n = 14) or physiological saline (control group, n = 10) was administered 5 minutes before 1 hour of middle cerebral artery occlusion in cats. The effects on the pial arteries and cerebral blood flow were observed continuously, followed by autoradiography for a quantitative measurement of cerebral blood flow 5 hours after middle cerebral artery recirculation. The volumes of the cerebral edema and infarct were estimated by planimetry from cerebral preparations made for histological examination. RESULTS: Pial arteries dilated by up to approximately 10% in the 400 micrograms group and 3% in the 200-micrograms group 30 minutes after administration of TA3090. Increases in cerebral blood flow of about 10% in the 400-micrograms group and 2% in the 200-micrograms group were demonstrated with laser Doppler flowmetry. In the second protocol, dilatation of pial arteries was significantly smaller during and after the ischemic insult in the treated group compared with the control group (p < 0.01). Cerebral blood flow decreased less significantly during ischemia (p < 0.01 at the end of ischemia) and increased less significantly after ischemia (p < 0.01 at the end) in the treated group compared with the control group. Autoradiography showed a more remarkable increase in cerebral blood flow due to luxury perfusion in the cerebral cortex, which was mainly perfused by the middle cerebral artery on the affected side in the control group (p < 0.01). Cerebral blood flow in the cerebral cortex, thalamus, and caudate nucleus on the contralateral side of the treated group increased by about 20% more than that of the control group (p < 0.05). Cerebral edema and infarction were much smaller in the treated group than in the control group (p < 0.01). CONCLUSIONS: 1) TA3090 dilates pial arteries and increases cerebral blood flow in normal brain regions in a dose-response fashion; 2) in ischemic regions compared with those in untreated animals, TA3090 results in a lesser reduction of cerebral blood flow during ischemia and in a lesser degree of hyperemia during reperfusion; 3) TA3090 is associated with less pial artery dilatation during ischemia, presumably due to improved collateral flow; and 4) the improved hemodynamic state with TA3090 is associated with significant reduction of cerebral edema and infarct size. PMID- 8506560 TI - Increased release of tumor necrosis factor-alpha into the cerebrospinal fluid and peripheral circulation of aged rats. AB - BACKGROUND AND PURPOSE: We earlier reported that risk factors for stroke prepare brain stem tissue for a modified Shwartzman reaction, including the development of ischemia and hemorrhage and the production of tumor necrosis factor-alpha, after a provocative dose of lipopolysaccharide. In the present study, we sought to determine whether blood and central nervous system cells of rats with the stroke risk factor of advanced age produce more proinflammatory and prothrombotic mediators than do those of young rats of the same strain. METHODS: Levels of tumor necrosis factor-alpha and platelet activating factor in the cerebrospinal fluid and tumor necrosis factor-alpha in the serum of 2-year-old and 16-week-old Sprague-Dawley rats were monitored before and after challenge with lipopolysaccharide. RESULTS: No consistent tumor necrosis factor-alpha activity was found in the cerebrospinal fluid or blood of control animals. Intravenous administration of lipopolysaccharide (1.8 mg/kg) increased serum tumor necrosis factor-alpha levels but had no effect on tumor necrosis factor-alpha in the cerebrospinal fluid. Serum tumor necrosis factor-alpha increased much more in aged rats than in young rats. When lipopolysaccharide was injected intracerebroventricularly, tumor necrosis factor-alpha activity in cerebrospinal fluid increased significantly more in old rats than in young rats. Baseline levels of platelet activating factor in cerebrospinal fluid were significantly higher in old rats than in young rats, and the levels increased to a greater degree in aged rats on stimulation. CONCLUSIONS: Rats with the stroke risk factor of advanced age respond to lipopolysaccharide with a more exuberant production of tumor necrosis factor-alpha and platelet activating factor than young rats of the same strain. These findings are consistent with our working hypothesis that perivascular cells are capable of exaggerated signaling of endothelium through cytokines such as tumor necrosis factor-alpha in animals with stroke risk factors. The effect of such signaling might be to prepare the endothelium of the local vascular segment for thrombosis or hemorrhage in accord with the local Shwartzman reaction paradigm. PMID- 8506561 TI - Paw-reaching, sensorimotor, and rotational behavior after brain infarction in rats. AB - BACKGROUND AND PURPOSE: Functional tests that are stable and consistent over time are an advantage for long-term evaluation of treatment in experimental stroke research. Because little information on this subject is available in rodents with focal cerebral ischemia, we investigated the outcome of three behavioral tests for a period of 3 months after the insult. METHODS: Spontaneously hypertensive rats were sham-operated (n = 27) or underwent an occlusion (n = 36) of the right middle cerebral artery. Before surgery all rats were tested for amphetamine induced rotational behavior, and half of the rats were trained in a paw-reaching task. One, 2, and 3 months after surgery the tests were repeated, together with a test for sensorimotor function. Infarct size was measured morphometrically. RESULTS: In the lesion group, total hemisphere area was reduced by 22%, caudate putamen by 47%, and the thalamus by 24%. Contralateral to the lesion, paw reaching was highly impaired, regardless of whether or not the rats had been pretrained, and lesion size correlated significantly to paw-reach performance. Ipsilateral rotation increased and sensorimotor function recovered with time in infarcted rats. CONCLUSIONS: In contrast to amphetamine-induced rotation and sensorimotor behavior, the paw-reaching test provides a stable behavioral parameter after a middle cerebral artery occlusion. Moreover, the lesion-induced deficit in paw-reaching is highly correlated to the extent of the infarct, suggesting that this test is useful in evaluating treatment effects for a longer period of time. PMID- 8506562 TI - Spinal infarction. A follow-up study. AB - BACKGROUND AND PURPOSE: Ten patients with spinal cord infarction were followed up after 1 to 27 (median, 3) years to establish the sequelae of the disease in the long term. SUMMARY OF REPORT: Eight surviving patients were interviewed about mobility, pain, and activities of daily living. All 8 patients had residual weakness in the legs; 7 of them were able to live at home without professional help. All but 1 suffered from continuous pain, which was not dependent on the degree of weakness. CONCLUSIONS: Motor function had improved to some extent in all patients, but pain is a disabling feature in the long term. PMID- 8506564 TI - Electric injury with cerebral venous thrombosis. Case report and review of the literature. AB - BACKGROUND AND PURPOSE: A case of accidental electrocution with previously unreported arteriographic evidence of cerebral vein thrombosis is presented. A brief description of early and late neurological complications and current theories attempting to explain the histopathological findings of electric injury are reviewed. The occurrence and persistence of late neurological complications are elucidated. CASE DESCRIPTION: A report of an accidental electrocution with 800 V of alternating current in a young man is presented. Cerebral angiography showed a cerebral vein thrombosis. The immediate complications included loss of consciousness, confusion, memory loss, and headache. Late complications of right sided clumsiness, sensory loss, hemianopsia, and neglect persisted for more than 1 year despite the brain being outside the current pathway. CONCLUSIONS: High voltage electric injury may cause cerebral vein thrombosis with significant early and delayed brain injury even when the brain lies outside the current pathway. PMID- 8506563 TI - Systemic giant cell arteritis and cerebellar infarction. AB - BACKGROUND AND PURPOSE: Systemic giant cell arteritis causing cerebellar infarction due to intracranial arteritis of the anterior inferior cerebellar artery has not been previously reported. We report this infrequent occurrence and discuss the differential diagnosis. CASE DESCRIPTION: An 85-year-old woman was admitted with a 2-week history of episodic ataxia, unilateral headaches, and vomiting. She had a history of atrial fibrillation and breast carcinoma. Her mental state was initially normal, and there were right-sided cerebellar signs. An ejection systolic murmur was heard, and peripheral pulses were palpable. A postmortem examination revealed cerebellar infarction due to giant cell arteritis of the anterior inferior cerebellar artery and basilar arteries. Systemic giant cell arteritis was also present. CONCLUSIONS: Giant cell arteritis is a systemic disorder that can infrequently involve intracranial vessels, including the basilar, vertebral, and anterior cerebellar arteries. Cerebellar infarction secondary to the arteritis may occur. The distribution and size of intracranial vessel involvement is distinct from isolated cranial angiitis. PMID- 8506565 TI - A case of tinnitus and hearing loss after cerebellar hemorrhage. AB - BACKGROUND: Approximately 10% of cases of hypertensive intracerebral hemorrhage are cerebellar hemorrhage. We report a case of intracerebellar hemorrhage in which the initial symptoms were hearing loss and tinnitus. SUMMARY OF REPORT: A 45-year-old man suddenly complained of hearing loss and tinnitus on the right side. Computed tomography demonstrated a high-density area 1.2 cm in diameter in the right cerebellar peduncle. Because of enlargement of the high-density area, the patient underwent surgery based on the diagnosis of hypertensive intracerebellar hemorrhage, and the hematoma was evacuated. The right-sided acoustic nerve was remarkably swollen by a subpial hematoma. CONCLUSIONS: In this case, hemorrhage of the right cerebellar peduncle extended to the eighth nerve through the subpial space, causing hearing loss and tinnitus. PMID- 8506566 TI - Cerebral blood flow and poststroke depression. PMID- 8506567 TI - Thrombolysis in acute ischemic stroke. PMID- 8506568 TI - Increased thromboxane biosynthesis in patients with acute cerebral ischemia. PMID- 8506569 TI - [Hand eczema]. PMID- 8506570 TI - [Incidence of hand eczema after surgical washing and use of surgical gloves]. AB - Contact dermatitis caused by surgical gloves is well known. Contact urticaria and anaphylactoid reactions among hospital personnel and patients following contact with latex gloves and glove dusting powder have previously been reported. A suspected increased frequency of hand eczema among personnel using detergents and surgical gloves in operating units initiated the present study. A questionnaire survey was performed in order to examine the frequency and degree of hand eczema among 332 surgeons and nurses working at the surgical units of Odense University Hospital during the period 1.6.-1.9.1989. A total of 242 persons (72%) answered the questionnaire. One hundred and fourteen persons (47%) claimed to develop skin discomfort or hand eczema following the washing procedure or use of surgical gloves. Among the personnel with skin problems 60% had spontaneously changed to another detergent/glove-product with subsequent clearing of the symptoms in 75% of the cases. Dermatological examination and patch tests were performed with European Standard series, gloves, rubber chemicals and selected soap components in 53 persons. Hand eczema was found in 16 persons (7%). Positive patch test reactions to latex gloves were found in four persons and only one person reacted to the rubber accelerators known to be present in the gloves according to the manufacturers' information. Among 26 persons with skin-discomfort and immediate symptoms, ten were prick tested with the standard battery of inhalant allergens, corn starch surgical glove powder, and extract of surgical gloves. Three persons reacted to glove extract, none reacted to glove powder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506571 TI - [A study of skin and mucosal irritation and incidence of allergy among office staff exposed to self-copying paper]. AB - At a public office with a staff of 129, twenty people work for short periods with large amounts of self-copying paper. A controlled study has shown a significantly higher incidence of pruritus and nasal congestion amongst staff exposed to large amounts of self-copying paper or its components, no drying of the skin after working with the paper and no increased degree of irritation of the skin were found in the study group at dermatological examination. No differences were found between the study group and the control group with respect to allergy or skin status or working conditions apart from the contact with self-copying paper. The study confirms that contact with fresh self-copying paper may result in pruritus and skin irritation, but allergy to the paper or microcapsule contents could not be demonstrated in this study. PMID- 8506572 TI - [Neurological complications of Mycoplasma pneumoniae infections]. AB - Mycoplasma pneumoniae (Mp) infections are well known for the classical clinical picture of primary atypical pneumonia. The infection shows a predilection for young age groups. Every fourth-fifth year Mp epidemics are seen, lasting several months particularly in autumn/wintertime. The last Mp epidemic in Denmark was seen autumn/winter 1991-1992. The central nervous system (CNS) is involved in less than 0.1% of all Mp infections, but among patients treated in hospital, CNS involvement occurs in up to 7%. Among patients with acute, febrile, nonbacterial CNS affection the incidence of Mp infections is shown to be 5%, with a maximum of 10% during Mp epidemics. In up to 20% the CNS complications are seen without preceding pulmonary symptoms. The pathogenesis is unknown, but probably involves several mechanisms. The spectrum of clinical findings is wide, ranging from mild meningeal signs to severe neurological symptoms and a poor outcome. Mp encephalitis has a particularly high morbidity and mortality. The effect of antibiotic treatment is doubtful, but the treatment is often instituted late. It may be debated, whether early antibiotic treatment can reduce the frequency of the CNS complications and their sequelae. Mp infection should be remembered as a differential diagnosis in any patient with fever and neurological symptoms. It can be recommended to add Mp diagnostic measures to the screening investigations, especially in patients with recent respiratory symptoms and during Mp epidemics. It is important to attempt to detect Mp by culture or polymerase chain reaction (PCR) from throat, respiratory tract and cerebrospinal fluid (CSF). Mp serology from blood and CSF should be performed early in cases where Mp infection is suspected. PMID- 8506573 TI - [Carbohydrate antigens and cancer]. AB - Studies of cancer are often based upon the idea that disease can be explained satisfactorily through insight into biochemistry and molecular biology, and that diseases follow regular patterns, so that, given full understanding of the biochemical environment, their course can theoretically be predicted. This has led to the hypothesis that cancer cells or their precursors may be defined by certain products described as tumor markers. The ideal marker is one that, when present, indicates that cancer will develop and, when absent, will exclude such a possibility. Research into tumor markers has become sweeter in recent years, in that aberrant glycosylation can be detected in most types of human cancers and in some premalignant lesions. Most studies have concentrated on changes seen in the structure of cell surface carbohydrates, although changes have also been found on secreted mucins, on stomal glycoprotein, and on serum glycolipids and glycoproteins. As the terminal part of these glycoconjugates is strongly immunogenic, changes here can easily be detected by antibodies selected on basis of their reactivity with biochemically well-characterized carbohydrates. Several studies have demonstrated that the expression of certain carbohydrates in specific tumors is related to tumor prognosis. Demonstration that carbohydrates are ligands for certain cell adhesion molecules is of special interest in this context as certain carbohydrates expressed in tumors bind to activated endothelial cells and clearly may be of importance for the formation of metastases. PMID- 8506574 TI - [Acute pancreatitis and gallstones]. AB - Gallstones are the most common causative factor in acute pancreatitis in the Western world. The majority of patients experience a mild course of the disease, with no need for acute invasive intervention. In patients with a severe course, acute endoscopic sphincterotomy seems indicated. Acute surgical intervention is not indicated in acute pancreatitis due to gallstones. In order to aim for early endoscopic decompression early detection og gallstones and determination of the severity og acute pancreatitis is essential. For this purpose, a combination of ultrasonography and biochemical tests seems most valid. Because of the high rate of recurrence, it is important that a cholecystectomy is performed during the same admission, after the acute symptoms have subsided. In patients with gallbladder stones an endoscopic sphincterotomy may be sufficient, but this procedure has never been compared to cholecystectomy in a controlled trial. Repeated ultrasonography is necessary, due to the high rate of false negative results of ultrasonography and biochemical tests in the early phase of acute pancreatitis. With a combination of repeated ultrasonography, endoscopic retrograde cholangiopancreaticography and microscopical examination of the bile a reduction in the incidence of acute "idiopathic" pancreatitis is achieved and appropriate treatment may be initiated. Finally, one should be aware of the presence of biliary sludge. Active intervention in patients with acute pancreatitis and biliary sludge significantly reduces the risk of recurrent pancreatitis. PMID- 8506575 TI - [Surgical treatment of snoring and sleep apnea]. AB - Twenty-one patients (four females and 17 males) greatly inconvenienced by snoring were subjected to UPP with CO2-laser technique. All patients were overweight (body-mass index average 30 kg/m2). Narrowing was found at the naso/oropharyngeal border in 71%. All had either abnormal uvula or soft palate. Snoring was reduced to a degree no longer socially troublesome in 17 patients. Three patients were still inconvenienced to some extent. Snoring was completely unchanged in only one patient. UPPP is not very difficult to perform, and we did not notice any sequelae of importance. We think that UPPP is an effective operation for severe snoring, although it does not eliminate the symptom. PMID- 8506576 TI - [Colonic ileus. Treatment of colonic ileus, a 10-year patient material]. AB - Morbidity and mortality have been evaluated in 238 patients with acute large bowel obstruction admitted over a ten year period. In two thirds, the cause of obstruction was a primary colonic carcinoma. Most of these patients (61%) had advanced disease and were over 70 years of age. Volvulus and cancer recurrences each accounted for 10%, and diverticulitis for eight percent. An overall mortality of 24% was found. Of 115 patients who had the obstructing lesion- primary carcinoma or diverticulitis--resected, a mortality of 8.7 was seen, higher for primary (14.9%) than for staged (4.4%) resections, in contrast the latter had a significantly longer hospital stay, 30 days as against 17 days when a primary resection was performed. Six non-lethal anastomotic leaks occurred. It is concluded, that patients with large bowel obstruction, most often caused by a colorectal carcinoma, are a high-risk group. In this retrospective study staged procedure compared with primary resection had lowest morbidity and mortality. PMID- 8506577 TI - [Risk of development of epileptic seizures in children with subclinical "epileptogenic" EEG abnormalities]. AB - Sixty-six non-epileptic children with focal spikes in EEG and without cerebral palsy were followed for 16 to 35 years. The cumulative risk of developing one or more seizures was 33% when the first abnormal EEG was recorded, and increased to about 80% if abnormalities persisted three or more years. Focal spike activity was most persistent in children with retarded development or with organic brain diseases. We conclude that the presence of focal EEG spikes in children without epileptic seizures can be considered epileptogenic, especially if the abnormality is persistent and associated with clinical evidence of organic brain disorder. PMID- 8506578 TI - [Incidence of HIV-1 antibodies in drug addicts autopsied at the Institute of Forensic Medicine in Copenhagen in 1988-1991]. AB - During the period 1988-1991 HIV-1-antibody tests were performed on a total of 389 autopsied drug addicts. The HIV-1-incidence rose from 6 per cent in 1988 to 14 per cent in 1990 and 14 per cent in 1991. There was no significant difference between the cumulated incidence in males and females. The HIV-1-positive addicts were compared to the HIV-1-negative addicts with respect to mean age, duration of abuse, residence and cause and manner of death. Except for residence, where significantly more HIV-1-positive than negative addicts lived in Copenhagen, there were no significant differences between the two groups. In about one third of the HIV-1-positive cases, equally for males and females, the HIV-1-positivity was not previously known. The results are discussed in relation to the findings in other countries and to the findings in selected groups of living addicts in Copenhagen. It is concluded that the diagnosis of HIV-1-infection in autopsied drug addicts is important from epidemiological and hygienic points of view. PMID- 8506579 TI - [Flow through the mitral and aortic ostium quantified with magnetic resonance velocity measurement]. PMID- 8506580 TI - [Microvascular reimplantation of the penis]. AB - A case of autoamputation of the penis is presented. Although the unique vascular properties of the penis have permitted good results in a number of cases of amputation of the penis, it is certain that the use of microreimplantation gives better results with a minimum of postoperative complications. PMID- 8506581 TI - [Pulmonary edema during terbutaline infusion against threatened premature labor]. AB - A case of pulmonary oedema during tocolytic therapy with terbutaline infusion is reported. Although a cardiogenic cause for this type of pulmonary oedema has never been proven, it is believed that physiologic changes in pregnancy aggravated by beta-2 stimulation together with fluid overload constitute the pathophysiologic background to this serious complication. PMID- 8506582 TI - [Formaldehyde in shampoos and creams]. PMID- 8506583 TI - [Chromosome abnormalities and malignant cells]. PMID- 8506584 TI - [Fatal AIDS hypocrisy and hidden lobbying]. PMID- 8506585 TI - [AIDS and behavior]. PMID- 8506586 TI - [Food expenses of patients with diabetes mellitus]. PMID- 8506587 TI - Localization of LAK cells and IL-2-stimulated regional lymph node lymphocytes by regional arterial infusion in renal tumor-bearing rats. AB - We describe the results of a traffic assay of the regional arterial administration of either lymphokine-activated killer cells or recombinant interleukin-2-activated regional lymph node lymphocytes in tumor-bearing rats in comparison with the results of systemic or intracardiac administration. The lymphocytes were labeled with 51Cr before infusion. The distribution and localization of these cells were serially evaluated by counting the radioactivity of the removed tissues. Concerning arterial administration, the labeled cells were directly infused into the abdominal aorta just proximal to the left renal artery. In the systemic or intracardiac route, the labeled cells preferentially localized to the lung, spleen and liver 2 h after injection. Radioactivity of the lung decreased thereafter and that of the spleen increased. In contrast, regional arterial administration yielded a remarkable accumulation of radioactivity in the left renal parenchyma 2 and 6 h after injection, similar to other distal organs tested. In the renal tumor model, the percentage radioactivity of the tumor tissue (% injectate recovered/g tissue) obtained at 6 h after injection in the arterial administration group ranged from 0.40 to 1.33, which was significantly higher (p < 0.05) than that in the systemic administration group. However, the radioactivity rapidly decreased from the tumor tissue 18 h after the injection. This study raises the essential issue on the mechanism of tumor destruction by lymphokine-activated killer lymphocytes in adoptive immunotherapy. PMID- 8506588 TI - Clinical prognostic factors in transitional cell cancer of the bladder. AB - A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for a mean of 9 years and the clinicopathological data were related to prognosis. The T category (p < 0.0001), N category (p < 0.0001) and M category (p < 0.0001) were the most important clinical prognostic factors, followed by the age of the patient (p < 0.0001). Of the histological variables the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the presence of R3-4 cells in voided urine (p = 0.0061) predicted unfavorable prognosis. In Ta-T1 tumors the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the age of the patient (p < 0.0001) had a prognostic value in univariate analysis. In Cox's analysis independent predictors of survival were the T category (p < 0.0001), WHO grade (p < 0.0001), patient age (p < 0.0001), papillary status (p = 0.012) and the presence of symptoms before diagnosis (p = 0.033). In superficial tumors the WHO grade (p < 0.0001) and patient age (p < 0.0001) were independent predictors of survival. PMID- 8506589 TI - MR angiography of renal cell carcinoma. AB - Seventeen patients with renal cell carcinoma were studied to evaluate the usefulness of gradient echo (fast low-angle shot), time-of-flight magnetic resonance (MR) angiography under breath-holding. By reconstruction of the data of consecutive coronal scans of the abdomen, in all 17 patients with renal cell carcinoma, MR angiography can delineate the abdominal aorta, inferior vena cava and renal arteries and veins simultaneously without any contrast materials. Our present study suggested that MR angiography is a useful imaging method for preoperatively assessing spacial vascular structures of the abdomen of patients with renal cell carcinoma. PMID- 8506590 TI - Sonography of urethral calculi. AB - We performed sonography in 7 males with membranous and posterior urethral calculi. Sonography demonstrated the urethral calculi in all 7 patients. These findings suggest that sonography is useful as a noninvasive screening technique for urethral calculi. PMID- 8506591 TI - Zinc, copper and oxalocalcic urolithiasis. AB - The possible effects of Zn and Cu in oxalocalcic urolithiasis were investigated. The formation of calcium oxalate crystals in the presence of Zn and Cu demonstrated that their morphology is clearly affected by these ions. Thus, when such ions were present in a number of higher concentrations, a notable increase in the primary aggregation was clearly detected. On the other hand, Zn and Cu urinary levels were determined in groups of stone-formers and healthy people. Zinc urinary concentration was significantly lower for lithiasic than for healthy people and the copper urinary concentration was lower for lithiasic than healthy males, but both female groups had a similar copper urinary concentration. The mentioned differences disappeared when serum levels were considered. These obtained results have been comparatively evaluated with those obtained by other authors. When considering all the commented aspects, it is concluded that no important direct action of zinc and copper on oxalocalcic calculi genesis takes place. PMID- 8506592 TI - Penile blood flow study in diabetic impotence. AB - Seventy-eight male diabetics with sexual dysfunction were evaluated by a thorough history, general physical, psychological, neurological and urological examinations, routine laboratory tests, and a duplex ultrasound scan with intracavernous injection of prostaglandin E1 (PGE1). The mean patient age was 55.9 years, and the average onset of sexual dysfunction was 10.0 years after the diagnosis of diabetes. Sixty-eight patients (87.2%) had moderate or severe cavernous arterial insufficiency. Older patients and those having a longer duration of diabetes had a higher incidence of cavernous arterial insufficiency. Cigarette smoking, hypertension, and alcohol abuse were also related to cavernous arterial insufficiency. There was no significant difference in cavernous arterial insufficiency between the insulin-dependent and the insulin-nondependent groups. There were significant differences of diameters and peak blood flow velocities of cavernous arteries between 78 diabetic impotent patients and 10 controls. These findings strongly suggest that the cavernous arterial insufficiency is closely related to the diabetic impotence. In addition, the prevalence of cavernous arterial insufficiency increases with age, duration of diabetes, cigarette smoking, hypertension and alcohol abuse, but it is not definitely correlated with the type of diabetes management. PMID- 8506593 TI - Role of warm water bath in inducing micturition in postoperative urinary retention after anorectal operations. AB - The relation of micturition to sitting in a warm water bath was studied in 30 healthy volunteers and 21 patients with urinary retention after hemorrhoidectomy. The rectal temperature, vesical and urethral pressures as well as the EMG activity of the external urethral sphincter were recorded before sitting in and immediately after getting out of the sitz bath at 40, 45 and 50 degrees C. In the 40 degrees C bath, 16 of the 30 normal subjects reported spontaneous micturition and 14 voluntarily induced micturition. The number of spontaneous micturitions increased with higher-temperature baths. Spontaneous micturition occurred in 19 patients with urinary retention when they sat in the sitz bath; 2 patients did not micturate and were catheterized. The urethral pressure in both the normal and retention subjects showed significant reduction which increased with higher temperature baths. There were no significant changes in the vesical pressure or EMG activity of the external urethral sphincter with water baths. Micturition on sitting in a warm water bath seems to be initiated by reflex internal urethral sphincter relaxation. A thermo-sphincter reflex is likely to be involved. PMID- 8506594 TI - Unilateral diffuse adrenal hyperplasia masquerading as aldosterone-producing adenoma in primary hyperaldosteronism. AB - We report a case of primary hyperaldosteronism due to unilateral diffuse hyperplasia. Unilateral adrenalectomy resulted in an improvement of hypertension and hyperaldosteronism. Six months after surgery, the plasma aldosterone level and plasma renin activity remained normal, but blood pressure returned to an abnormally high level. We have reviewed the literature and discuss the pathogenesis of this disorder. PMID- 8506595 TI - A solitary renal mass as the only manifest lesion of a B-cell lymphoma. AB - A patient with a solitary renal mass as the only manifest lesion of B-cell lymphoma was reported. The surgical specimen revealed that the lesion was histologically limited to the renal parenchyma. Liver dysfunction prevented him from receiving systemic chemotherapy. Mediastinal and mesenteric lymph node involvements developed 6 months later. Fortunately, the patient survived without recurrence for 18 months after the surgical removal of these tumors and intensive chemotherapy. Systemic chemotherapy is recommended on patients with renal lymphoma even if the tumor seems to be limited to the organ. PMID- 8506596 TI - Primary malignant melanoma of the bladder. A case report and literature review. AB - We report on a case of primary melanoma within a diverticulum of the urinary bladder. The primary nature of this neoplasm was demonstrated through meticulous clinical and radiological examination. The incidence, prognosis and differential diagnosis of this urothelial melanoma are discussed. PMID- 8506597 TI - Massive prolapsing orthotopic ureterocele. AB - A ureterocele may prolapse through the external urethral meatus and present as an interlabial mass. We report a case of a prolapsing ureterocele measuring 10 cm in diameter. PMID- 8506598 TI - Efficacy of fenbendazole and piperazine against developing stages of toxocara and toxascaris in dogs. AB - In a series of controlled trials involving 59 naturally infected greyhounds, fenbendazole at a dose rate of 50 mg/kg/day for three consecutive days reduced the overall numbers of third and fourth stage Toxocara canis by 94.0 per cent and third stage, fourth stage and immature adult stages of Toxascaris leonina by 92.4 per cent. In contrast, piperazine at 100 mg/kg had little or no useful effect against the larval stages of T canis and T leonina and variable efficacy against immature adult T leonina. Fenbendazole was also 100 per cent effective against immature Trichuris vulpis. In a separate controlled experiment, puppies in three litters exposed to reinfection with T canis were treated with fenbendazole at two weeks old and again only after their mean faecal egg counts exceeded 200 epg. Between one and three doses were required to suppress the output of eggs during the puppies' first 12 weeks of life. PMID- 8506599 TI - Factors affecting the clinical outcome of injuries to the superficial digital flexor tendon in National Hunt and point-to-point racehorses. AB - Ultrasonographic examination was used to define the severity of injuries to the superficial digital flexor tendon in 73 National Hunt or point-to-point racehorses and the factors influencing the outcome of the cases were examined. Thirty-four of the horses (46 per cent) returned to work with an average time out of training of 13.5 months. The rate of recurrence of the injury was 35 per cent. The severity of the lesions was related to the outcome; all the mildly affected horses returned to work, with 63 per cent of them racing and an average time out of training of 10.2 months; 50 per cent of the moderately affected horses returned to work, and 30 per cent raced with an average time out of training of 11.3 months; 30 per cent of the severely affected horses worked, and 23 per cent raced with an average time out of training of 18.3 months. The differences in outcome between unilateral and bilateral injuries within each severity group were not statistically significant. Seventy-six per cent of horses treated with polysulphated glycosaminoglycans returned to work, compared with 46 per cent of conservatively managed horses and 50 per cent of horses treated with laser therapy. However, these differences were not statistically significant and the rate of recurrence of the injury in the horses treated with polysulphated glycosaminoglycans was 50 per cent compared with only 31 per cent in the conservatively managed horses. Seventy per cent of the mares and 47 per cent of the geldings were retired from racing. PMID- 8506600 TI - Dissolution of obstructive urethral uroliths in a ram. PMID- 8506601 TI - Anthrax in cattle, wildlife and humans in Zambia. PMID- 8506602 TI - Canine distemper virus isolated from a captive seal. PMID- 8506603 TI - Further loss of UK products. PMID- 8506604 TI - Megabacteriosis in exhibition budgerigars. PMID- 8506605 TI - Mycobacterial infections in cats. PMID- 8506606 TI - Conjunctival instillation of scrapie in mice can produce disease. AB - Mice were infected with one of two strains of scrapie by instilling brain homogenate into the conjunctiva to establish whether infection could be initiated. Of the 55 mice infected with ME7 scrapie, 23 developed clinical disease 323 +/- 8 (mean +/- standard error) days later. Three out of 12 mice infected with 79A scrapie developed disease after 232 +/- 35 days. The ME7 incubation period is similar to that for the oral route of infection. We feel that these results emphasize the need for adequate eye protection when handling tissues infected with spongiform encephalopathies. PMID- 8506607 TI - Serological titers of equine monocytic ehrlichiosis associated with gastro intestinal disorders and serological follow-up on two endemic farms. AB - The purpose of this work was to study the association of positive serological titers to Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (EME) with gastro-intestinal disorders in hospitalized horses referred to The Ohio State University College of Veterinary Medicine Teaching Hospital (OSU VMTH). In addition, serological titers for E. risticii were monitored in two horse populations with endemic EME for one season to monitor temporal changes in titers. A statistically significant difference was found between the proportion of the total hospitalized horse population presented with a gastro-intestinal disorder during the study period, and study horses with IFA titers > or = 1:80 with these signs (P < 0.05). No such difference was found between the proportion of the total hospital horse population presented with signs of gastro-intestinal disorder, and the study horses with IFA titers of 1:20 1:40 with these signs, suggesting that these titers may not have any clinical significance for EME (P > 0.05). Thirty-eight horses on two farms endemic for EME were tested approximately every 3 weeks, 33 of which were tested serially at least two times. Five of the 38 horses (13.2%) had IFA titers > or = 1:80--two that were positive initially and three that seroconverted during the study; 15 horses' titers fluctuated between negative (IFA titers < 1:20) and exposed titers (1:20 through 1:40); and 18 horses remained negative throughout the study. PMID- 8506609 TI - Antibiotic-resistance and plasmids in Staphylococcus hyicus isolated from pigs with exudative epidermitis and from healthy pigs. AB - A total of 100 S. hyicus strains isolated from healthy piglets and piglets with exudative epidermitis originating from 100 different herds was examined for drug resistance and prevalence of plasmids. Resistance to macrolide/linosamide antibiotics could be related to plasmids in 55 (93%) of the 59 resistant strains: A plasmid of 2.4 kb mediating resistance to macrolides and lincosamides was observed in 25 strains, and a plasmid of 11.5 kb mediating resistance to both macrolides/lincosamides and tetracycline was observed in 30 strains. A plasmid with a molecular weight of 4.5 kb was shown by curing experiments to be associated with resistance to tetracycline in 12 strains. All together, 47 strains were resistant to tetracycline. In 42 (89%) of these strains tetracycline resistance was found to be encoded by plasmids. Fifty six strains were resistant to streptomycin, and resistance was associated with the presence of a 4.4 kb plasmid in 17 strains studied. Resistance to penicillin, observed in 44 strains, and resistance to kanamycin, observed in 15 strains, could not be related to plasmids in any of these strains. The 11.5 kb plasmid was observed in 39% of the strains isolated from piglets with EE, and in 7% of the strains isolated from healthy piglets. Despite its higher prevalence in strains from piglets with EE, the 11.5 kb plasmid could not be shown to encode production of capsule or exfoliative substances: factors which might play a role in the development of exudative epidermitis in piglets. PMID- 8506608 TI - In vitro proliferation of a canine granulocytic Ehrlichia. AB - Canine granulocytic Ehrlichia sp., an agent which parasitizes the neutrophilic leukocytes in dogs, was transiently propagated in vitro. Dogs were experimentally inoculated with blood containing canine granulocytic Ehrlichia. Bacteremias in experimentally infected dogs varied from 1.2 to 9.3% granulocytes infected. Granulocytes from experimentally infected dogs were harvested and cultured in the presence of RPMI 1640 medium supplemented with fetal bovine serum, conditioned medium, and HEPES buffer. The percentages of granulocytes containing ehrlichial morulae increased significantly with time for 2 to 4 days, with at least one culture from each dog achieving 20% of granulocytes infected. Granulocytes taken from infected dogs early in bacteremia yielded cultures with the greatest percentage of infected cells. By 5 days post-infection the percentage of infected granulocytes decreased as did leukocyte viability. Attempts to maintain the in vitro cultures for prolonged periods by addition of uninfected granulocytes failed to increase the number of infected host cells, suggesting that no new infections were initiated and that observed increases in the percentage of infected cells in in vitro cultures were due to growth of the organism in granulocytes that were infected in vivo. PMID- 8506610 TI - Characteristics of coagulase-negative Staphylococci isolated from bovine intramammary infections. AB - Coagulase-negative Staphylococci (CNS) isolated from 86 different bovine intramammary infections (IMI) were investigated for their plasmid content, antimicrobial resistance, and infection characteristics. Plasmids were isolated from 30.2% of CNS. Number of plasmid bands ranged from 1 to 5. With the exception of tetracycline resistance, the presence of plasmids was not related to antibiotic resistance. Staphylococcus chromogenes was the CNS most frequently isolated from bovine IMI. Intramammary infections were of long duration (mean = 222 days) and resulted in a low incidence of clinical mastitis (8.1% of IMI). The greatest percentage of IMI (55%) were detected in heifers with 57% of these IMI first detected at calving. A total of 56% of IMI originated during the dry period in second lactation or older cows. The number of plasmid-positive CNS IMI was greater (P < 0.05) in multilactational cows when compared to heifers. The presence of a plasmid-positive CNS had no influence on duration of IMI, origin of IMI, clinical status of the infection, and elimination of IMI. PMID- 8506611 TI - Interactions of porcine lymphocytes with Campylobacter-like organism membranes purified from proliferative enteropathy. AB - Peripheral blood mononuclear cells prepared from 6 healthy pigs and 6 pigs apparently affected by proliferative enteropathy were incubated with dilutions of a sonicate of purified Campylobacter-like organisms 872/87 prepared from a separate case of proliferative enteropathy. Incubations were carried out in RPMI 1640 medium, supplemented with foetal calf serum, L-glutamine, sodium pyruvate and 2-mercaptoethanol for 5 days, with relevant concanavilin A and medium controls. Marked stimulation of lymphocyte proliferation was clearly evident in samples prepared from the pigs apparently affected by proliferative enteropathy (peak stimulation index 4.4-13.2) compared to the healthy pigs (peak stimulation index 3.0). Diagnosis of proliferative enteropathy in these naturally derived cases was confirmed by a specific IgM indirect immunofluorescence assay. The results suggested that a specific antigen-related mitogenesis of blood lymphocytes occurs in pigs affected by proliferative enteropathy. This may have implications for immunization regimes. PMID- 8506612 TI - Monitoring experimental swine dysentery: rectal swab blood test and Serpulina (Treponema) hyodysenteriae detection. AB - In two experiments, ten postweaning piglets were inoculated intragastrically with cultures of Serpulina (Treponema) hyodysenteriae strain B204 and were individually monitored for swine dysentery. Eight control animals received sterile culture medium. Between the day of inoculation and 35 days later, rectal swab samples were assayed for fecal blood by means of a commercial test kit and for S. hyodysenteriae cells by direct (phase contrast) microscopy and selective culture methods. Optimal detection of S. hyodysenteriae required both microscopy and culturing. Of 41 rectal swab samples positive for fecal blood, 38 (93%) were positive by direct microscopy, by selective culture, or by both techniques. Of 118 samples negative for fecal blood, 115 (97%) were negative by direct microscopy, by selective culture, or by both techniques. Swab samples from control swine were negative for fecal blood. The fecal blood test was a convenient and reliable method for objectively monitoring individual animals with experimental swine dysentery. The occult blood test used in these studies might be generally useful for veterinary surgeons to monitor and diagnose swine intestinal disorders in which fecal blood is produced. PMID- 8506613 TI - Quantification of histamine in plasma and pulmonary fluids from horses with chronic obstructive pulmonary disease, before and after 'natural (hay and straw) challenges'. AB - A commercial radioimmunoassay kit was used to quantify histamine concentrations of plasma, bronchoalveolar lavage fluid (BALF) and pulmonary epithelial lining fluid (PELF) of normal horses and horses with chronic obstructive pulmonary disease (COPD), before and after 'natural (hay and straw) challenge' (NC). There were no significant changes in the concentrations of histamine in plasma or BALF at 0.5 or 5 h after NC, but the PELF histamine concentration of COPD affected horses was significantly increased at 5 h, but not at 0.5 h, following NC. As the histamine concentrations of whole BALF lysates were significantly correlated with the numbers of metachromatically staining cells, presumed to be mast cells and/or basophils, these findings support involvement of a late phase, IgE mediated, hypersensitivity reaction in the pathogenesis of equine COPD. PMID- 8506614 TI - Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques. AB - Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIV mac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed 1, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+ CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4+CD8+ immature thymocytes, and a relative increase in both CD4+ and CD8+ mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line. PMID- 8506615 TI - Avidity of antibody and agglutinability of antibody-sensitized latex in latex agglutination test. AB - This paper describes the avidity of IgG antibody used for preparation of latex sensitized with IgG antibody (IgG-sensitized latex) and the agglutinability of IgG-sensitized latex in slide reversed passive latex agglutination (RPLA). Using immunodiffusion techniques, it was found that anti-canine C-reactive protein (CRP) sera from four rabbits immunized with canine CRP had the same antibody titers. However, the antibodies had different levels of avidity. When lattices were sensitized under the same condition with the IgG antibodies of different avidity levels separated from the above-mentioned antisera using Protein A and canine CRP-Sepharose 4B immunosorbent, these demonstrated different patterns of agglutinability in slide RPLA. The latex sensitized with IgG antibody of higher avidity demonstrated a stronger agglutinability. PMID- 8506616 TI - Modulation of the intracellular survival of Brucella abortus by tuftsin and muramyl dipeptide. AB - Tuftsin, a physiologic bioactive peptide of animal origin, and muramyl dipeptide, a synthetic bioactive glycopeptide of microbial origin, are known to enhance several recognized macrophage functions and increase non-specific resistance of the host against a number of pathogens. The influence of these two bioactive peptides was studied in permissive bovine mammary macrophages that were unable to control the intracellular replication of Brucella abortus and restrictive bovine mammary macrophages that were able to effectively reduce the intracellular survival of B. abortus. Addition of tuftsin (Thr-Lys-Pro-Arg) or muramyl dipeptide significantly (P < 0.03) enhanced the ability of the permissive macrophages to control the intracellular replication of B. abortus strain 2308 and resulted in the functional conversion of the permissive macrophages into restrictive macrophages. Addition of tripeptide tuftsin fragment (Lys-Pro-Arg), a natural inhibitor of tuftsin, to the medium completely abrogated the effect of tuftsin (P < 0.03). No additive effect on the ability of the macrophages to control the survival of B. abortus resulted from the combination of tuftsin and muramyl dipeptide. PMID- 8506618 TI - Efficient preparation of monospecific anti-canine C-reactive protein serum and purification of canine C-reactive protein by affinity chromatography. AB - The canine C-reactive protein (CRP) fraction isolated from canine acute-phase serum on a phosphorylcholine-Sepharose 4B column was further subjected to Sephacryl S-300 gel filtration. A canine CRP fraction not containing IgM was then obtained. The antisera, obtained after several immunizations with this canine CRP fraction, contained nonspecific antibodies that reacted with albumin, transferrin and IgG in addition to CRP. This antiserum could be easily changed to monospecific canine CRP serum, when it was subjected to absorption for only 15 min using glutaraldehyde-insolubilized normal canine serum protein containing 3.5 micrograms ml-1 of CRP. Pure canine CRP was isolated with a recovery rate of 95% from canine acute-phase serum by affinity chromatography using specific anti canine CRP antibody. PMID- 8506617 TI - Detection of mucosal immune responses in chickens after immunization or infection. AB - In order to measure mucosal antibody responses in the chicken intestine an ELISA based assay was developed that was able to detect antigen-specific antibodies in an isotype-specific way. Locally produced antibodies could be detected after overnight culture at 37 degrees C. In particular the production of IgA, more than IgM and IgG, was significantly increased by immunization of the animals with K99 pilus antigen or by infection with Eimeria tenella parasites. Data presented here indicate that the assay can be used to estimate the magnitude of the mucosal antibody response in experimental conditions where antibody levels in bile or intestinal contents were not significantly changed. PMID- 8506619 TI - Atypical immunoproliferative disorders: when of age? PMID- 8506620 TI - Significance of p53 expression as a prognostic factor in oesophageal squamous cell carcinoma. AB - The tumour suppressor gene product p53 is believed to play an important role in the progression of human malignant tumours through mutation and over-expression. Using a microwave oven heating method, we have detected over-expression of p53 in buffered-formalin fixed, paraffin-embedded sections of oesophageal carcinomas immunohistochemically and examined the relationship between the p53 over expression and postoperative survival. Employing a monoclonal antibody (pAb1801), nuclear p53 was detected in 56 of 105 (53%) tumour specimens. Homogeneous, heterogeneous, and focal immunostaining patterns were noted. No immunostaining was found in adjacent benign tissues. The results in buffered-formalin fixed sections were similar to those in the frozen sections. The cumulative survival rate of patients with p53 expression was significantly lower than that of the patients without expression (P < 0.05), even though there were no significant differences between the clinicopathological features of the two groups. The results indicate that the nuclear accumulation of p53 might be an independent prognostic factor in patients with oesophageal squamous cell carcinomas. PMID- 8506621 TI - Granulomatous reaction and tissue remodelling in the cutaneous lesion of chromomycosis. AB - The cell-mediated immune reaction was studied in the cutaneous lesion of chromomycosis, using monoclonal antibodies against polymorphonuclear neutrophils, macrophage and lymphocyte subsets, endothelial and fibroblast cells. In addition, immunostaining of the main degradative enzymes (neutrophil elastase and interstitial collagenase) and certain important cytokines (transforming growth factor-beta, tumour necrosis factor-alpha and interferon-gamma) suggested an explanation for the granulomatous reaction and the associated tissue remodelling. The distribution pattern of neutrophils and macrophage subsets, observed by computer-aided image analysis, suggests that the in situ persistence of fungi is the main pathological factor. PMID- 8506622 TI - Longitudinally oriented smooth muscle cells in rabbit arteries. AB - Intima formation in vessels, spontaneous or experimentally induced, is generally characterized by the presence of longitudinally oriented smooth muscle cells (LSMC). During an experiment of neo-intima induction in carotid arteries in rabbits, by application of a non-constrictive silastic cuff, a study was performed to investigate the presence of LSMC in the systemic and pulmonary circulations, in both elastic and muscular arteries. Three patterns could be distinguished: intimal cushions in muscular arteries, single or small groups of LSMC in the intima in elastic and larger muscular arteries, and intra-medially located layers or columns of LSMC in the aorta, the pulmonary artery, at the bifurcation of the aorta and around orifices of branches. In order to understand this peculiar orientation a biomechanical approach was used: this showed that near the lumen the circumferential stress is 4.5 times higher than the longitudinal. Because the cell surface of the smooth muscle cells exposed to this stress per unit vessel length is much less in the longitudinal than in the circular direction we conclude that the LSMC align in the direction which allows them to cope most effectively with the mechanical stresses. PMID- 8506624 TI - Foamy spheroid bodies in the globus pallidus and the substantia nigra pars reticulata: an investigation on regional distribution in 56 cases without neurodegenerative diseases. AB - In order to clarify the sites of predilection for foamy spheroid bodies (FSBs) their regional distribution was studied in 56 persons (30-98 years) without neurodegenerative diseases. Variable amounts of FSBs were observed in approximately 30% of cases and favoured the rostro-ventral parts of the globus pallidus (GP), including the ventral pallidum, and/or the substantia nigra pars reticulata (SNr). The results strongly suggest that FSBs develop during aging and are a hitherto undescribed pathological hallmark for degeneration of the GP and the SNr. PMID- 8506623 TI - Nature and significance of calcium oxalate crystals in normal human thyroid gland. A clinicopathological and immunohistochemical study. AB - To elucidate the significance and nature of calcium oxalate crystals in the thyroid, we studied these crystals clinicopathologically and immunohistochemically in 182 normal thyroids from patients autopsied within 5 h of death. Under polarized light, calcium oxalate crystals showed brilliant birefringence and were invariably found within the colloid. The crystals were found in 73.1% of all cases but were more prevalent and denser in older individuals, with the highest prevalence (85.2%) being observed in those over 70 years of age. No crystals were seen in those under 10 years of age. Although underlying diseases seemed to have little influence, post-mortem delay apparently affected the prevalence and density of occurrence since the crystals tended to disappear with hours after death. An immunohistochemical study using anti-thyroid hormone antibodies revealed that the crystals were within negatively or weakly stained colloid and were not common in strongly stained colloid. These findings support the hypothesis that the occurrence of calcium oxalate crystals in normal human thyroid is associated with a low functional state of the thyroid follicles. PMID- 8506625 TI - Alpha-smooth muscle actin and other stromal markers in endometrial mucosa. AB - Stromal-epithelial interactions as expressed by alpha-smooth muscle actin (alpha SM actin) collagen type IV, fibronectin, laminin and tenascin were studied in normal and pathological endometrial mucosa. There was complete or incomplete cuffing of scattered endometrial glands by alpha-SM actin mostly in the basal layer of endometrial mucosa and in dilated or cystic glands. Individual adenocarcinomatous glands were not encircled by alpha-SM actin-positive cells. Collagen type IV and laminin were found surrounding all glands irrespective of the presence of periglandular alpha-SM actin. Fibronectin was diffusely present in the stroma. Tenascin was identified, albeit not exclusively, in a periglandular location similar to that of alpha-SM actin. We conclude that the periglandular cells staining for alpha-SM actin, which were negative for cytokeratins, are probably myofibroblasts (MFs). Since this phenomenon was most commonly observed in dilated and cystic glands, we suggest that stromal cells immediately surrounding these glands may be subjected to mechanical or other stress resulting, as in other situations of tissue remodelling, in the development of MFs. This may also explain the appearance of tenascin in the same location. Thus, our finding may represent a further example of the local modulation of stromal cell phenotype, possibly under the action of micro environmental factors. PMID- 8506627 TI - Three familial cases of fundic gland polyposis without polyposis coli. AB - We report three cases of fundic gland polyposis in the stomach identified in three patients who were related. Grossly the numerous polyps covered an area limited to the body and fundus of the stomach, no polyps were found in the antrum, duodenum, colon, or rectum, and histologically, the gastric lesions consisted of numerous hamartomatous polyps, characterized by proliferation of the fundic and cystic glands. The gastric lesions were identified in families without polyposis coli. This type of fundic gland polyposis has never been documented before in the literature. PMID- 8506626 TI - Myopathy and hypertrophic cardiomyopathy with selective lysis of thick filaments. AB - We present a undescribed condition in a girl who died at 8 years of hypertrophic cardiomyopathy. Muscle and endomyocardial biopsies disclosed a selective loss of thick filaments ultrastructurally. In muscle biopsy histochemical abnormalities of myofibrillar AT-Pase were confined to type 1 fibres. Gel electrophoresis of muscle homogenate showed no qualitative abnormalities of slow and fast myosin heavy chains (MHC) and light chains, and the amount of the different myosin isozymes was in agreement with histochemical myofibrillar ATPase findings. The pathogenetic mechanisms have not been elucidated in this case but we suspect an abnormality of the beta-cardiac MHC gene, the only gene expressed in the heart and in type 1 skeletal muscle fibres. PMID- 8506628 TI - Horizontal saccades to dichoptically presented targets of differing disparities. AB - Horizontal saccades were elicited to targets of various disparities displayed dichoptically. When the left eye and right eye targets were in the same hemifield, the resulting saccade demonstrated spatial averaging (42%, where 50% represents perfect averaging) between the left and right eye target positions. When the left eye and right eye targets were in opposite hemifields, the saccade was directed to one of the stimuli and was only minimally influenced by the presence of the other. This pattern is similar to that obtained when saccades are made to double targets, both of which are visible to both eyes. These data are discussed in terms of an ecological role for the global effect. PMID- 8506629 TI - Nonlinearity and oscillations in X-type ganglion cells of the cat retina. AB - Intracellularly recorded light-responses of X-type ganglion cells in the cat retina were separated, with the help of a wavelet method, into "slow" membrane ("G")-potentials and the corresponding spike trains. In response to sinusoidally modulated high intensity light spots with different sizes and frequencies, X-type ganglion cells show both oscillations correlated with the stimulus frequency and other, faster, oscillations that were not always locked to the stimulus. A forced van der Pol oscillator model with stimulus-dependent coefficients proved to describe the empirical findings quite well. A linearity-coefficient of the equations indicates strong nonlinearity at a temporal frequency of 8 Hz with spot sizes on the order of 0.5-0.7 deg and decreasing nonlinearity at lower temporal frequencies or smaller spot sizes, while the faster oscillations become more prominent. We could not determine whether the oscillations are intrinsic to the cell-membrane or generated by (or in interaction with) the preganglionic retinal meshwork. The results show that X-cell spike-trains can contain oscillations that are not phase-locked to the stimulus and that are therefore virtually invisible after stimulus synchronous averaging. It is not likely that these retinal oscillations directly induce the well described oscillations in cat visual cortex, since they usually fall in a different frequency range. PMID- 8506630 TI - Light-dark discrimination after sciatic nerve transplantation to the sectioned optic nerve in adult hamsters. AB - In adult golden hamsters (Mesocricetus auratus), the optic nerve was bilaterally sectioned with one side grafted with the sciatic nerve to make a bridge to the ipsilateral superior colliculus. Shuttle-box avoidance was tested using light as the conditioned stimulus. Three of the five transplanted animals revealed statistically significant increase in percentages of avoidance. A significant increase in the avoidance scores was also observed in 15 normal hamsters, but none of 13 blind hamsters showed such an increase. Intertrial responses, which represent spontaneous responses, did not show significant changes. We conclude that some of the transplanted animals can discriminate between light and dark, probably through their restored visual pathway. PMID- 8506631 TI - Motion sensitivity and spatial undersampling in amblyopia. AB - The nature of the visual deficit in human amblyopia has been keenly sought over the last decade. Some confusion has arisen as to whether the motion-sensitive mechanisms known to exist in normal vision are selectively affected in humans with amblyopia. To address this issue we compare contrast thresholds for detection and direction discrimination of drifting sine-wave gratings in a group of humans with amblyopia. The results suggest that over the vast majority of the spatio-temporal range, direction of motion can be discriminated at detection threshold. Over a narrow part of the visible range there is a differential loss of sensitivity for direction discrimination over that of simple detection. However such an effect also occurs for normal vision under spatially scaled conditions and it seems likely that it is mediated by non-motion sensitive mechanisms. We show that one possible cause of this loss of direction discrimination, namely spatial undersampling within the central region of the amblyopic visual field, is not a viable explanation. PMID- 8506632 TI - Spatial and temporal properties of illusory figures. AB - The best known example of illusory figures is the Kanizsa triangle consisting of three disks with a sector removed. The disks and sectors are arranged so that they form the corners of a triangle. Although the sides of the triangle are not physically present, they are clearly visible to the observer. In this study the effect of sequential presentation of the inducing disks on an illusory (Kanizsa) triangle was investigated. The task of each subject was to find, by the method of adjustment, the longest critical duration that allowed perception of the illusory triangle produced by presenting the three inducing disks sequentially. We varied the sizes and/or separations of disks. An illusory triangle produced by flashing the three inducing disks simultaneously for 33 msec served as a comparison stimulus. Our experiments showed that increasing the inducing disk size or reducing the inter-disk distance increased critical duration. The result means that the shorter the illusory contour to be induced the longer the critical duration and vice versa. Thus, if the inductive disks are less separated in space they can be more separated in time and vice versa. These findings seem to agree with the suggestion that illusory contours emerge from the synchronization of gamma-waves emitted by the neurons in the visual cortex. PMID- 8506633 TI - Spatial integration of band-pass filtered patterns in noise. AB - Contrast energy thresholds were measured for noisy band-pass filtered Sloan letters, K, H, O, and a plus symbol (+) at various centre frequencies and bandwidths. For all patterns the efficiency and energy sensitivity of detection increased with filter bandwidth but decreased with increasing filter centre frequency. Hence, neither parameter alone can explain the changes in efficiency and energy sensitivity. Irrespective of centre frequency and bandwidth, efficiency and energy sensitivity were found to decrease as a single power function of image complexity (Z) defined as the product of the square of the median spatial frequency (fm) of the image energy spectrum and image area (A95) comprising 95% of total contrast energy of the stimulus. The product Z = fm2A95 describes image complexity in the sense that when f2m or A95 increase the number of details increase, too. The decrease of the efficiency of detection with increasing image complexity suggests that the proportion of the integrated image area decreases as the complexity of an image increases. PMID- 8506634 TI - On the confounding effects of phosphor persistence in oscilloscopic displays. AB - Phosphor persistence has been a source of confounding in studies of temporal integration in vision. We examined the confounding by assessing the effects of the persistence of two commonly-used phosphors (P15 and P31) on performance of a temporal-integration task. In one experiment we eliminated the visibility of phosphor persistence by closing two mechanical shutters upon display termination. In a second experiment we estimated the duration of phosphor persistence by displaying the image behind closed shutters which opened upon display termination. No detectable persistence was every produced by P15 phosphor. By contrast, P31 phosphor produced persistence that lasted several hundred milliseconds even when a veiling light was projected on the screen. We ascribe the earlier instances of confounding to inadequate interpretation of the technical data on phosphor decay. PMID- 8506635 TI - Interaction of stereo, texture and outline cues in the shape perception of three dimensional ridges. AB - We report five psychophysical experiments that employed a cue conflict paradigm to investigate integration by the human visual system of surface shape information from stereo, texture and outline cues. The experiments used convex parabolic and triangular three-dimensional ridge stimuli, with amplitudes (base to peak) in the range 3-9 cm, viewed from 57 cm. The observers' task was to judge ridge amplitude using a scale of two-dimensional drawings of ridge profiles. Cue integration was studied using both vertically and horizontally oriented ridges and both real ridges and stereograms of ridges. The main findings were: (a) stereo strongly dominated all horizontal ridge stereograms; (b) texture and outline cues strongly dominated low (3-6 cm) but not high (9 cm) amplitude vertical ridge stereograms; (c) stereo strongly dominated all real ridge stimuli. These results are evidence against explanations of the vertical/horizontal stereo anisotropy which propose that it derives from stereo mechanisms being tuned only to disparity cues with non-zero second-order spatial derivatives or to disparity discontinuities. They also show that radically different results can be obtained when stereo mechanisms are explored using stereograms and real surfaces and possible reasons for this are discussed. PMID- 8506636 TI - On the loss of apparent motion between isolated chromatic stimuli near isoluminance. AB - Long range apparent motion (AM) between two isolated stimuli breaks down following prolonged inspection. Time-till-breakdown (TTB) for AM between random dot squares (red or green) on a red random-dot background was measured as a function of luminance contrast of the stimuli against the background. For the same-color (red squares on the red background) and the different-color (green squares on the red background) conditions, TTB showed clear dependence on the luminance contrast, diminishing with decreasing the contrast. Near isoluminance (luminance contrast of approx. -14 to +14%), AM for the same-color condition disappeared, but AM for the different-color condition was clearly seen and persisted for 7-14 sec. These results show that AM can be produced by color alone. Previous controversial question on the loss of long range AM near isoluminance may be explained by taking into account the contrast dependence of the breakdown effect and the experimental procedures employed. PMID- 8506637 TI - Aging and neural spatial contrast sensitivity: photopic vision. AB - This study investigated the extent to which older adults' loss in spatial contrast sensitivity at a photopic level is attributable to neural changes in the aged visual system. Laser interferometry was used to generate interference fringes which bypass the optics of the eye in presenting a grating target on the retina. Older adults in good eye health exhibited on average a small but statistically significant loss (0.1-0.2 log unit) in contrast sensitivity across the spatial frequency range tested, although there was considerable overlap between young and old adults. This loss in contrast sensitivity for interference fringes accounted for less than half of the photopic contrast sensitivity loss at higher frequencies reported for older adults in studies using conventional direct viewing techniques in which the optics of the aged eye are not bypassed. We conclude that neural changes in the aged visual system have a rather minor contribution to older adults' loss in spatial contrast sensitivity at a photopic level. PMID- 8506638 TI - Temporal aspects of depth contrast. AB - Depth contrast is a contrasting change in the depth of a feature that results from changes in the disparities of other objects in the field of view, even though the disparity of the original feature remains unchanged. Depth contrast effects decrease during continuous viewing of the stimuli and may disappear altogether after several minutes unless the disparities of the inducing features change with time. This fading occurs whenever the inducing features have constant disparity, whether they are stationary or oscillating laterally. Depth contrast effects occur whenever the inducing features are visible within half a second before or after presentation of the test features. When test features are enclosed by a rectangle which is just inside of a circumscribing outer trapezoid, the inner rectangle "shields" the test features from the depth-inducing effects of the outer trapezoid. Surprisingly, this shielding effect persists if the inner rectangle and outer trapezoid have the same slant direction, but fades with time if the slants are opposite in direction. PMID- 8506639 TI - Forward pattern masking and adaptation: effects of duration, interstimulus interval, contrast, and spatial and temporal frequency. AB - Eight experiments are described that compare pattern adaptation and forward pattern masking by examining the effects of five variables on the contrast threshold of a target presented after an adapter or masker. The target is a Gabor pattern with a center frequency of 2 c/deg and a duration of 33 msec. Thresholds are determined using an adaptive spatial forced-choice method. Principal results are as follows. (1) An adapt-refresh regime with a 2 sec refresh and a 2 sec recovery period on each trial is shown to maintain constant performance. (2) Desensitization is very rapid, reaching near maximum in < 200 msec. (3) Recovery is very rapid during the first 100-200 msec and then very slow with the rate of slow recovery decreasing as adapter/masker duration increases. (4) Threshold vs contrast functions are step-like for certain frequency pairs. (5) Sensitivity vs frequency functions derived from adapting and masking are similar in form. (6) Masker temporal frequency (0-15 Hz) has very little effect. These results are described by a theory that postulates that the target is detected by a few mechanisms that are differentially tuned to spatial frequency. The effect of both a forward masker and an adapter is to desensitize the mechanisms that respond to it. Recovery is a weighted sum of two decay processes, one fast and one slow. The theory fits the data from both paradigms well with some differences in parameters. PMID- 8506640 TI - The effect of contour closure on the rapid discrimination of two-dimensional shapes. AB - An outline drawing often serves as an excellent depiction of a visual scene. Somehow, our visual system can form two- and three-dimensional percepts solely from one-dimensional contour information. In mathematics, contour closure plays a key role in bridging this dimensional gap, however in perception the link between closure and shape is unclear. To better understand this relationship, we devised a set of visual search experiments in which subjects discriminate outline figures by means of their two-dimensional shape. By modulating the degree of closure of the outlines, we show that two-dimensional shape processing is rapid for closed stimuli but slow for open stimuli. We further show that search can be characterized as a smooth, monotonic function of the degree of closure, supporting the notion of a perceptual closure continuum. PMID- 8506641 TI - Lateral interactions between spatial channels: suppression and facilitation revealed by lateral masking experiments. AB - We measured contrast detection thresholds for a foveal Gabor signal flanked by two high contrast Gabor signals. The spatially localized target and masks enabled investigation of space dependent lateral interactions between foveal and neighboring spatial channels. Our data show a suppressive region extending to a radius of two wavelengths, in which the presence of the masking signals have the effect of increasing target threshold. Beyond this range a much larger facilitatory region (up to a distance of ten wavelengths) is indicated, in which contrast thresholds were found to decrease by up to a factor of two. The interactions between the foveal target and the flanking Gabor signals are spatial frequency and orientation specific in both regions, but less specific in the suppression region. PMID- 8506642 TI - Simple exponential functions describing the absorbance bands of visual pigment spectra. AB - Literature data for visual pigment spectra are formally treated by assuming that the spectra consist of a summation of absorbance bands, that the shape of the bands is invariant according to the Mansfield-MacNichol transform and that this shape is described by simple exponential functions. A new template for constructing visual pigment spectra from peak wavelengths is derived. PMID- 8506643 TI - What happens if it changes color when it moves?: psychophysical experiments on the nature of chromatic input to motion detectors. AB - Several lines of evidence indicate that the processing of motion by the primate visual system continues even when a moving stimulus differs from its surroundings by color alone. To illuminate the mechanisms by which our visual system uses color as a token for motion correspondence, we have developed an "apparent motion" paradigm in which red/green sine-wave gratings undergo reversal of chromatic contrast sign each time they are displaced in a particular direction. Under such conditions, correspondence based upon conservation of chromatic sign conflicts with correspondence based upon chromatically-defined borders. When these heterochromatic stimuli also possess luminance modulation, motion is always perceived in the direction in which the sign of luminance contrast is preserved. At isoluminance, however, two very different chromatic influences on motion detection are revealed. First, when stimuli undergo small spatial displacements, motion is perceived in the direction of the nearest chromatically-defined border even when the sign of chromatic contrast at that border alternates over time. Under these conditions, motion detectors apparently exploit information about image borders defined by color while sacrificing information about the colors that make up those borders. By contrast, when spatial displacement is large, motion is more apt to be perceived in the direction for which sign of chromatic contrast is preserved. In this instance, information about the polarity of chromatic contrast facilitates motion detection. These results suggest that chromatic signals contributing to motion detection are of two distinct types. This conclusion has implications for the degree of crosstalk between magnocellular and parvocellular processing streams in the primate visual system and it reinforces our understanding of how image features affect the way we see things move. PMID- 8506644 TI - Visual mechanisms that signal the direction of color changes. AB - Evidence is presented for a visual capacity specialized to sense the chromatic direction of change in colors over time. Discrimination thresholds were measured between pairs of suprathreshold color changes presented in consecutive intervals. In one interval, the color of a spatially uniform disk was changed at a constant speed along the circumference of a circle in an equiluminant color plane. In the other, an instantaneous change, which can be described as a vector in the equiluminant plane, was added to the circular color modulation. Averaging across conditions showed that the threshold for discriminating between a pair of purely temporal color changes was approximately proportional to the cosine of the color angle between them. The model that is presented to account for these results is based on parallel directional-color mechanisms that are tuned to different directions in color-space and are responsive to change in one color direction but not its opposite. PMID- 8506645 TI - A multi-stage color model. AB - The first stage of our model has three cone types, with L:M:S cones in ratios of 10:5:1. In the second stage, retinal connectivity leads to three pairs of cone opponent, and one pair of cone-nonopponent systems. At a third (cortical) stage of color processing, the S-opponent cells are added to or subtracted from the L- and M-opponent units to split and rotate the one effective parvo geniculate response axis into separate RG and YB color axes, and separate luminance from color. We also discuss changes with eccentricity, and connectivity based on correlated neural activity. PMID- 8506646 TI - Higher-order structure in regularity detection. AB - In three experiments a simple Euclidean transformation (reflection, translation, rotation) was applied to collections of twelve dots in such a way that they contained equal lower-order structure, defined on the pairwise grouping of elements with their partner following transformation (e.g. parallel virtual lines), but differed in the presence vs absence of higher-order structure, defined on pairs of pairwise groupings (e.g. virtual quadrangles with correlated angles). Based on the much better performance levels (d') in the case of additional higher-order structure, we conclude that global regularities are easier to detect when the local correspondences are supported by higher-order ones formed between them. These enable the lower-order groupings to spread out across the whole pattern very rapidly (called bootstrapping). As a preliminary attempt to specify these principles, we proposed a working model with two basic components: first, a function expressing the cost of a perceptual grouping or the lack of regularity, and, secondly, an algorithm based on simulated annealing to minimize the cost function. The simulation results obtained with our current implementation of these principles showed satisfactory qualitative agreement with human regularity detection performance. Finally, the theory was shown to capture the essence of a large number of grouping phenomena taken from diverse domains such as detection of symmetry in dot patterns, global structure in Glass and vector patterns, correspondence in stereoscopic transparency and apparent motion. Therefore, we are convinced that, in principle, the mechanism used by the human visual system to detect regularity incorporates something like bootstrapping based on higher-order structure. We regard this as a promising step towards unraveling the intriguing mechanisms of classic Gestalt phenomena. PMID- 8506647 TI - Inhomogeneity and anisotropies for motion detection in the monocular visual field of human observers. AB - Signal-to-noise-ratio (SNR) thresholds were measured for the detection of coherent motion in moving random pixel arrays of constant root-mean-square contrast (35%) and constant average luminance (48 cd/m2) for 8 or 16 directions of motion at 25 positions in the visual field of the right eye. Five observers took part in this perimetric study of motion detection. The 24 eccentric positions were chosen on 8 equally spaced radial lines at the eccentricities 6, 24, and 48 degrees, the 25th position was centred on the fovea. At these positions we analysed the threshold SNR-value as a function of motion direction alpha. A significant modulation of the threshold with alpha is called an anisotropy. Anisotropies were found for low to medium velocities at positions on and near the vertical meridian, where the thresholds proved to be highest for vertical motion directions (up or down). On the horizontal meridian no significant anisotropies were found. Also on the oblique radials anisotropies were found, especially at 225 degrees (lower nasal quadrant of the visual field, upper temporal quadrant of the retina), but these were milder than those on the vertical meridian. The diameter of the stimulus is an important parameter and its influence was explored, albeit incompletely. Also inhomogeneities were found. This is defined as a consistent modulation of the threshold SNR-value with position A, the position along an equi-eccentricity circle (A-inhomogeneity), or with eccentricity E (E-inhomogeneity) or both. A simple acuity-scaling optimized for the nasal retina takes care of most of the E-inhomogeneity, but an A inhomogeneity stays rather prominent. It too is characterized by higher thresholds near the vertical meridian than near the horizontal meridian. The findings suggest that iso-threshold curves are elliptical or egg-shaped with their long axis on the horizontal meridian and shifted somewhat out of naso temporal symmetry towards the nasal half of the retinal field. As with the anisotropies the inhomogeneity grows in amplitude for decreasing velocity below medium velocity values of 1-2 pixels/frame, but in contradistinction to the anisotropies it is present and even increases in amplitude for increasing velocities above these medium values of 1-2 pixels/frame as well. The results are discussed in the light of other perimetric studies of motion detection and acuity, in the light of a model postulating the cooperation of groups of velocity tuned bilocal motion detectors, and in the light of recent ideas on structure and function of primate cortical areas and processing streams. PMID- 8506648 TI - Evidence for second-order motion detectors. PMID- 8506649 TI - Shifts of visual attention at fixation and away from fixation. AB - Attention shifts in the visual field were investigated using a task in which two numerals were flashed one by one, the duration of each numeral being 33 msec. Both numerals were followed by a mask pattern (100 msec in duration). The observer was asked to report the two numerals. If the observer correctly recognized both numerals, it implies that he was able to perform a simple act of attention shift from one item to the next. In the foveal experiment, both numerals were presented at fixation--the second numeral on top of the first. In the extrafoveal experiment, the numerals were also flashed sequentially but in different locations: the first numeral was at fixation and the second at 7 deg eccentricity. The results showed that the observers could not shift attention away from fixation to an extrafoveal position as efficiently as they could maintain attention at fixation. PMID- 8506650 TI - Transparent motion from feature- and luminance-based processes. AB - The apparent motion of a discretely displaced complex waveform with a periodic contrast modulation or "beat" of frequency f and sinusoidal components of frequencies 3f and 4f was examined at various interstimulus intervals (ISIs). At short ISIs perception of motion of both the beat and an aliased component of the waveform results in transparent motion. At longer ISIs motion is perceived only in the direction of the features of the waveform. The transparent motion observed at short ISIs indicates that, under certain conditions, "short-range" motion sensors do not constrain "long-range" feature processing and both may be active simultaneously. PMID- 8506651 TI - Effects of luminance and exposure time on contrast sensitivity in spatial noise. AB - Using gratings with and without spatial noise we measured r.m.s. contrast sensitivity as a function of (i) retinal illuminance, (ii) amount of light added onto the screen, and (iii) exposure time. Our experiments showed that contrast sensitivity in external spatial noise was independent of decreasing retinal illuminance and exposure time as long as contrast sensitivity was lower with noise than without. Thereafter the decrease of contrast sensitivity was identical with and without noise. Although contrast sensitivity without external spatial noise was independent of the amount of added light, contrast sensitivity in external spatial noise was found to increase with the amount of added light until it reached the sensitivity measured without noise. Thereafter contrast sensitivities with and without noise were identical. Our results (i) provide experimental evidence for the validity of the generally accepted hypothesis that in the human contrast detection mechanism signal-to-noise ratio is constant at threshold and (ii) indicate that external spatial noise is the principal source of noise when it reduces contrast sensitivity. PMID- 8506652 TI - Subjective colour from achromatic flicker. PMID- 8506653 TI - Spatial frequency adaptation and contrast gain control. AB - Spatial frequency adaptation is shown to cause a decrease in the exponent of the power law describing contrast increment thresholds. Next we show that spatial frequency adaptation produces almost no threshold elevation at a 30 msec test duration but a normal threshold elevation at 500 msec. Control experiments rule out an explanation in terms of sustained and transient mechanisms. Together these results show that spatial frequency adaptation cannot result from neuronal fatigue. The data can be explained by a contrast gain control network in which unit responses provide feedback signals that divide input contrast. Adaptation is hypothesized to produce an increase in the strength of this divisive feedback via temporary synaptic modification. A simple network model fits the data and also predicts both the magnitude and temporal dependence of the tilt aftereffect. PMID- 8506654 TI - [The concept of internal medicine and specialization in internal medicine]. PMID- 8506655 TI - [New developments in the treatment of non-specific intestinal inflammation]. AB - This term comprises idiopathic proctocolitis (IPC) and regional enteritis (RE, Crohn's disease). Despite a number of similarities (similar age, symptoms, immunology, drugs), the two conditions differ substantially (site, pathology, surgery) and thus from a practical aspect it is essential to differentiate them. The term "ulcerative colitis" comprises also other inflammations, e.g. recently identified infections with causal agents which are difficult to diagnose. There are also several types of regional enteritis which differ as to their course and sequelae. As regards medical treatment, in both conditions in particular corticosteroids are used and 5-aminosalicylic acid. An important novelty are 5 aminosalicylic acid tablets with prolonged action; different types are used depending on the site of the disease. Surgical treatment differs not only as to its frequency but also by the type of operation. In regional enteritis operations confined to the affected site are used, while in idiopathic proctocolitis standard operations are available: proctocolectomy, colectomy with an ileorectal anastomosis, with continent ileostomy or with an ileoanal anastomosis and reservoir. The latter is preferred nowadays. PMID- 8506656 TI - [Early diagnosis of gastric cancer]. AB - Endoscopic diagnosis completed by biopsy achieved remarkable accuracy. New trends -endoscopy with the use of ultrasound orange red porphyrin fluorescence elicited by blue light e. g. krypton laser and strip biopsy not only greater accuracy of endoscopic methods but also open up new therapeutic possibilities. Histochemical and histoenzymatic methods allow to classify histological findings of the norm (presence of pepsinogen and neutral glycoprotein) of atrophic gastritis with intestinal metaplasia (acid glycoprotein, activity of sucrose, alkaline phosphatase-AP, leucin-aminopeptidase-LAP) and of dysplasia (presence of sulfomucin, decrease of AF, LAP, sucrose and trehalase activity) and to divide them into well defined groups. We are able to distinguish which mucosal changes are suspect, we know that malignant transformation can after a certain period of time be expected approximately 2-14% yet we still do not know whether the period from dysplastic change to malignant transformation is not longer than malignant change in resected stomach. Epidemiologic and experimental data gives us enough reasons for dietary and chemopreventive measures (apart of other treatment) especially in risk groups patients. PMID- 8506657 TI - [Therapy of peptic ulcer]. AB - After a historical review of therapeutic methods of peptic ulcer the author discusses contemporary views on therapy. As a basis he uses the idea that Helicobacter pylori is the decisive factor for the development of peptic ulcers. Therefore the basis of treatment should be its eradication by bismuth salts. Despite this at present the basis of treatment are antagonists of H2 receptors. Economic aspects are important. In repeatedly relapsing ulcers with evidence of Helicobacter pylori the author recommends eradication by a combination of drugs. PMID- 8506658 TI - [Secondary osteopenia in gastrointestinal diseases]. AB - Of 2557 patients with osteopenia examined during the past 17 years 1707 were classified as secondary osteoporosis and 406 as osteomalacia. Diseases of the gastrointestinal tract participate as the cause of osteoporosis in 635 patients (37.19%) and osteomalacia was the cause in 210 patients (51.72%). The highest ratio in osteoporoses are lactose intolerance--256 cases (14.99%); maldigestion was recorded in 305 patients (17.86%). This category comprises gastrectomies of both types, severe affections of the gallbladder and biliary pathways, insufficiency of the external pancreatic secretion, patients with frequent exacerbations of ulcerative colitis. Resections of the small intestine are on the borderline between maldigestion and malabsorption. Malabsorption alone was found in 74 patients (4.33%) and there is also sprue, M. Crohn, diverticulosis of the small intestine, diabetic enteropathy and scleroderma. In secondary osteomalacia the leading cause is hepatic damage recorded in 167 patients (41.13%) and malabsorption in 43 patients (10.59%). PMID- 8506659 TI - [Diagnosis and therapy of esophageal diseases]. AB - In reflux disease the authors emphasize the following diagnostic procedures: a satisfactory case-history, endoscopy, aimed biopsy, radiographic evidence of reflux, radionuclide reflux scintigraphy and pH-metry. As to subsidiary examinations, they recommend Bernstein's perfusion test. In 50% of the patients with non-coronary chest pain the complaints are caused by diseases of the oesophagus. The latter include achalasia, dysphagia, idiopathic diffuse spasm, hyperdynamic oesophagus and irritable oesophagus. In the treatment of reflux disease the stage of the disease is decisive. Treatment is prolonged and the doses of drugs are higher than in duodenal ulcers. The basis are H2 blockers. In severe forms treatment with omeprazole is indicated. Surgery is indicated only in severe mucosal complications. In achalasia of the oesophagus this is disruption of the sphincter by the method of pneumatic dilatation or surgical myotomy. Idiopathic diffuse spasm and other disorders of oesophageal motility respond in different ways to treatment with calcium autagonists and nitrate treatment. PMID- 8506660 TI - [The effect of creatine phosphate (Neoton) in acute myocardial infarct (a prospective multicenter pilot study]. AB - The authors investigated in a group of 106 patients with a first myocardial infarction treated by thrombolysis the effect of i.v. administration of creatine phosphate (a new drug with cardioprotective action--Neoton Alfa Schiapparelli Wassermann Co). In the course of treatment electrocardiographic changes were recorded and the presence of arrhythmias examined by the Holter technique. The Neoton group displayed a statistically insignificant but nevertheless obvious trend of electrocardiographically less serious forms of infarction and a lower incidence of infarctions, as compared with the control group. PMID- 8506661 TI - [Protective effect of Neoton during cardiovascular surgery. Hemodynamic and biochemical aspects]. AB - The authors present the preliminary results of an experimental study where to a group of patients (n = 10) subjected to cardiosurgery, using extracorporeal circulation, to the cardioplegic solution creatine phosphate was added (Neoton of Alfa Schiaparelli Wasserman Co.)--2 g.l-1. The authors investigated haemodynamic and biochemical parameters and compared them on the day of operation with the same parameters assessed in a group of controls operated in the same way but without addition of creatine phosphate to the cardioplegic solution. Apart from insignificant differences in haemodynamic parameters the group of patients given Neoton had a lower malondialdehyde level during the early stage after termination of extracorporeal circulation, spontaneous defibrillation, a lower incidence of dysrhythmias and disorders of the conduction system. It can be assumed that creatine phosphate (Neoton) may be effective in the protection of the myocardium from ischaemia reperfusion damage. PMID- 8506662 TI - [The effect of creatine phosphate in patients after surgery in ischemic heart disease]. AB - The authors submit their experience with the use of creatine phosphate in patients operated on account of coronary heart disease. They divided 50 consecutive patients into three groups. Group A--controls, group B--creatine phosphate was added to the filling of the apparatus for extracorporeal circulation and group C--creatine phosphate was added to Bretschneider's cardioplegic solution. During operation and during the early postoperative period the CK and CK MB levels were evaluated as well as levels of free acid radicals, the haemodynamic state of the patients, the incidence of ventricular dysrhythmias, the need of defibrillation, histological and histochemical examinations. The authors found a lower CK and CK MB level, a lower percentage of ventricular dysrhythmias and the same haemodynamic results of the operation in patients with a more markedly impaired systolic function of the left ventricle when creatine phosphate was used. Creatine phosphate did not affect the morphology of the heart muscle nor the level of the assessed myocardial enzymes. PMID- 8506663 TI - [The optimal diagnostic approach in myocardial infarct]. AB - In the submitted review the authors discuss rational criteria for the diagnosis of myocardial infarction, indications for thrombolysis, coronarography and possibly PTCA, the method of indirect (non-invasive) assessment of an occluded coronary artery and the most frequent mistakes in the diagnosis of infarction. Essential examinations in the acute stage of myocardial infarction are: case history, ECG, CK-MB (possibly echocardiography). For indication of thrombolysis of acute PTCA case-history and ECG (or echocardiography) are sufficient. Indications of early coronarography before discharge from hospital: postinfarction angina pectoris, malignant arrhythmia (except on the first day), haemodynamic instability, evidence of myocardial ischaemia (restricted symptoms) during a maximal load before discharge. PMID- 8506664 TI - [Arrhythmia in acute myocardial infarct]. AB - The authors present a review of optimal treatment and prevention of dysrhythmias in the acute stage of myocardial infarction (AIM). They emphasize the necessity to shorten the pre-hospitalization stage of the disease (the prevalence of malignant dysrhythmias culminates) and elaborate in every hospital region an optimal plan of emergency care (ensure CPR, electrical defibrillation, pharmacological prevention of VT and VF). They draw attention to the fundamental importance of the therapeutic limitation ensuing from the size of the focus which implies at the same time prevention and treatment of an impaired cardiac rhythm. The authors recommend early recanalization treatment with subsequent anti thrombocytic treatment, and if contraindications are absent, standard administration of beta blockers in the early stage of AIM. They draw attention to the asset of anti-arrhythmic treatment as well as to its undesirable effects. They discuss also indications and complications of temporary transvenous cardiac pacing. PMID- 8506665 TI - [The present status of nitrates in the treatment of ischemic heart disease]. AB - The authors describe the development of nitrates from substances of the first generation (nitroglycerin and isosorbit dinitrate) to the second generation (isosorbit-5-mononitrate). They explain the mechanism of their action, haemodynamic effects and the problem of nitrate tolerance. Indications of their rational use are given. PMID- 8506666 TI - [The stress interview after acute myocardial infarct]. AB - Patients suffering from myocardial infarction (MI) form the high risk group. Residual ischemia, impaired left ventricular function and dysrhythmias are life endangering. Sudden death is more frequent in this group than in the one of patients with CHD. Therefore before discharge from the hospital we applied to the patients after MI series of noninvasive methods to disclose ventricular dysrhythmias. 136 patients after MI, mean age 56 (36-74), were examined. From those 90 patients underwent early exercise test and stress interview--application of common and specific mental stress. Holter ambulatory monitoring was applied to 18 post MI patients and echocardiography to 23 ones. A control group constituted 20 apparently healthy men, mean age 54 (44-64), which underwent exercise test and stress interview too. We have shown the incidence of ventricular dysrhythmias is always significantly higher (p < 0.01) in the post IM group than in the healthy one at exercise test and stress interview. The incidence in the post MI group is 49.4% at specific stress, 38.2% at common stress and 34.5% at exercise test. Significantly higher is the incidence at specific stress than at common stress or early exercises test, respectively (p < 0.05). Patients with dysrhythmias at both mental stresses have significantly lower exercise performance and workload at exercise test narrow correlation with disclosure at Holter monitoring is observed. Stress interview aids identification of risk group of post MI patients with serious ventricular dysrhythmias and demonstrates importance of psychotherapeutic care after MI. This method of mental stressing completes noninvasive test s and it is good way to II. phase of rehabilitation after myocardial infarction. PMID- 8506667 TI - [24-hour monitoring of blood pressure in patients with essential hypertension]. AB - The aim of the study was to determine the efficiency of enalapril therapy during 24-hours blood pressure monitoring. A group of healthy subjects (C, n = 11), a group of patients with essential hypertension without therapy (EH, n = 9) and a group of patients with essential hypertension II (WHO) treated with enalapril (Acepril Lachema) in once a day doses (13.0 +/- 2.1 mg per kg) during at least 10 months (EH A, n = 8). In all groups of patients and healthy subjects 24-hours blood pressure measurement was provided using Accutracker II equipment. The mean values of systolic (SBP) and diastolic blood pressure (DBP) from 24-hours measurement (+/- SD) were in the group of healthy subjects C 121.38 +/- 10.49/74.79 +/- 7.88 mmHg, in the group EH 146.58 +/- 12.20/88.0 +/- 8.97 mmHg, in the group EH A 127.38 +/- 8.36/74.71 +/- 6.08 mmHg. The differences between the maximum and minimum mean blood pressure values during 24 hours (SBP/DBP) were in the group C 33/27 mmHg, EH 37/29 mmHg, EH A 29/21 mmHg. The smaller difference in SBP and DBP in EH A patients was significant in comparison to C and EH (t test, p < 0.05). Cosinor analysis proved the results. From our results we can conclude that the Acepril therapy decreases blood pressure more during the day hours then during night and it is preferable in connection to the risk of night hypotension with hypoxia. PMID- 8506668 TI - [Pharmacologic therapy of hyperlipoproteinemia and its pitfalls]. AB - Hyperlipoproteinaemias, in particular those associated with hypercholesterolaemia are considered one of the most significant risk factors for the development of early atherosclerosis and ischaemic heart disease. Effective reduction of plasma lipids and lipoproteins is associated with a decline in the prevalence of ischaemic heart disease and cardiovascular mortality. Pharmacotherapy of hyperlipoproteinaemias is therefore considered a rational procedure in preventive cardiology. After a brief review of comprehensive treatment of hyperlipoproteinaemias the author discusses in particular contemporary possibilities of their medicamentous treatment. He emphasizes hypolipidaemic agents most frequently used at present, i. e. statins, resins and fibrates. When selecting hypolipidaemic agents several basic data must be taken into account: values of the lipid metabolism, the effect of the hypolipidaemic agent on individual parameters, undesirable effect of the drug, tolerance on the part of the patient, as well as whether after prolonged treatment regression of atherosclerosis or a decline in the prevalence of ischaemic heart disease was recorded. Decision taking is influenced also in a major way by the price of the preparation. The author discusses therefore also the effectiveness of hypolipidaemic agents in relation to their price. On these data the basic recommendation for pharmacotherapy of hyperlipoproteinaemias is based. The author discusses in more detail some controversial problems of treatment of hyperlipoproteinaemias, treatment of children, women and old patients. Attention is devoted also to patients with isolated low HDL-cholesterol levels and patients with elevated triglyceride levels. PMID- 8506669 TI - [Cardiovascular changes in Turner's syndrome]. AB - 25 adult asymptomatic patients with Turner's syndrome were evaluated by clinical examination, ECG, M-mode and two-dimensional echocardiography and 24 h Holter monitoring. Patients with Turner's syndrome had a significantly higher resting heart rate (83.3 versus 73.7/min in controls, p < 0.01) and a shorter PQ interval (122.3 ms versus 147.1 in controls, p < 0.01). The short PQ interval was not associated with the karyotype (45,X vs. mosaic karyotypes and structural abnormalities of X and Y chromosome), hypertension, estrogen treatment, or congenital valvular abnormalities. No significant arrhythmias were present. On 24 hours ambulatory ECG monitoring the frequency of ectopic supraventricular and ventricular activity was identical as in published controls. The congenital heart abnormalities were detected in 8 (32%) women with T.sy, however, during the follow-up they became significant in only two (8%) of them. PMID- 8506670 TI - [Myocardial metabolism during ischemia]. AB - The heart muscle is critically dependent on energy supply from oxidative phosphorylation, which in turn requires an adequate oxygen supply. Its greatest proportion (80%) is used by mechanical work of the heart, followed by the ion pumps and protein resynthesis. Global ischaemia of the isolated heart leads within two seconds to the electron transport arrest in mitochondria and at the same time glycogenolysis, an alternative energy source, is accelerated. The content of macroergic phosphate declines rapidly, in particular that of creatine phosphate and within 10-15 seconds mechanical activity stops. The subsequent fate of ischaemic tissue depends on the degree and period of ischaemia. Very brief ischaemia (1-2 min.) does not cause any functional sequelae after restoration of the arterial blood supply. Longer ischaemia (10-15 min.) leads during reperfusion to postischaemic dysfunction (stunned myocardium, G. R. Heyndrickx) which is completely reversible. Prolonged hypoperfusion lead to mechanical dysfunction, which may last weeks and months but is reversible (hibernated myocardium--S. H. Rahimtoola). Only prolonged critical ischaemia (30-60 min. and perfusion as low as 0.15 ml/min./g tissue) leads to necrosis of muscle cells. Its development is enhanced in particular by an extensive drop of macroergic phosphates with inhibition of anaerobic glycolysis, excessive amounts Ca++ in cardiomyocytes and cumulation of catabolites, such as lactate, H+ and free radicals. PMID- 8506671 TI - [Silent myocardial ischemia. Status in 1992]. AB - Silent myocardial ischaemia is found in 5% of a completely symptom-free population, in 30% of patients with a history of myocardial infarction and in 60 to 100% of patients with stable or unstable angina pectoris. Only one fifth to one quarter of episodes of myocardial ischaemia is associated with angina pectoris which means that 75% to 80% of episodes take a silent course. Episodes of myocardial ischaemia take place at lower heart rates than during exercise test and they are induced by common, everyday activities of the patient. So far it is not known why some episodes of myocardial ischaemia are silent while others are associated with angina pectoris. No differences were found in the duration or extent between silent or symptomatic myocardial ischaemia. Patients with frequent episodes of silent myocardial ischaemia have in general an elevated threshold of pain perception. A certain role is probably also played by the increased secretion of endogenous opioids--endorphins. The finding of myocardial ischaemia during ambulatory monitoring of ECG is of prognostic value regardless whether ischaemia is associated with angina pectoris. This applies in patients with unstable angina pectoris where ST depressions may be found during Holter monitoring of the ECG even when pain is controlled by treatment, and this finding is associated with more serious coronarographic findings and a poorer prognosis. The position is similar in patients with stable angina pectoris where episodes of depression of the ST segment during ambulatory ECG monitoring are associated with a poorer prognosis and this finding does not depend on the result of the electrocardiographic exercise test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506673 TI - [The stress test in nuclear cardiology--present status]. AB - In nuclear cardiology the exercise test is used above all to assess the diagnosis when ischaemic heart disease is suspected and to assess the extent and site of ischaemic heart disease. The objective of the submitted paper is to present new possibilities in this area where more perfect technical equipment and new methodological approaches contribute new quality to clinical decision taking. Greatest attention is devoted to tomographic analyses of perfusion of the heart muscle during the exercise test. PMID- 8506672 TI - [Myocardial infarct in type II diabetes]. AB - Myocardial infarction is encountered in diabetic patients more frequently and is usually associated with a higher mortality rate, as compared with the normal population. The authors investigated the relationship between myocardial infarction and diabetes in a group of 408 patients with myocardial infarction, incl. 144 (32%) type 2 diabetics most of them treated by diet or PAD. In the group of diabetics with myocardial infarction a higher incidence of hypertension was recorded and more frequent use of nitrates. The incidence of obesity, smoking angina pectoris, a previous infarction with a pain-free course and family-history were comparable in the two groups. Diabetic patients suffered significantly more frequently from non-Q infarction of the heart muscle (p < 0.5) and infarctions of the anterior wall (p < 0.001). The mortality during hospitalization was 24% in the group of diabetics, while it was 17% in non-diabetic patients. PMID- 8506674 TI - [The antihypertensive effect of isradipine and additional pharmacodynamic effects]. AB - The authors demonstrated that isradipine reduces the blood pressure assessed at rest in patients with mild to medium severe hypertension. The antihypertensive action was enhanced by administration of beta-blockers. In a loading test the pressor response to strain was reduced in particular as regards diastolic pressure; from this in may be concluded indirectly that a vasodilatating effect is involved. The authors recorded a rise of plasma renin activity which may be associated with previous vasodilatation. Parameters of lipid metabolism were influenced by isradipine. The indifference of isradipine as regards the effect on functions indicated by biochemical screening was again confirmed in the present investigation. The undesirable effects typical for calcium antagonists were manifested in a very small percentage of the investigated subjects and in a small number of repeated examinations. The reason for discontinuation of treatment in one patient was an effects which does not threaten the patient (flush). Isradipine is an effective antihypertensive drug with very good tolerance. PMID- 8506675 TI - [Helicobacter pylori in the etiology of ulcer disease and gastritis]. AB - Helicobacter pylori (Hp) is unequivocally the most frequent cause of antral gastritis and most probably participates in the majority of cases in the aetiology of gastritis affecting the body of the stomach. The close relationship between antral gastritis and duodenal ulceration is documented by the high incidence of Hp in these patients (90-100%). The problem of Hp negative cases of duodenal ulceration was not finally resolved yet. The absence of Hp in duodenal ulcer usually implies a different aetiology (NSAID, gastrinoma etc.). Hp is eliminated by a number of drugs (bismuth preparations, some antibiotics, metronidazole), however, eradication (Hp negativity after a month or longer following termination of treatment) is ensured so far only by a combination of several drugs. Less clear are the relations with gastric ulcers. The presence of Hp in the antral mucosa is substantially smaller, however, when the mucosa near the ulcer is examined it is also almost 100%. The relationship of antral gastritis and non-ulcer dyspepsia is not quite clear. Hp is found in about half the patients and its elimination (e.g. by bismuth preparations), has a favourable impact on inflammatory changes as well as on the patient's complaints. The regression of complaints is more permanent than after antacids which have only a favourable effect on complaints but not on Hp and the inflammation. PMID- 8506676 TI - [Substitution therapy in insufficient external pancreatic secretion]. AB - For assessment and monitoring of adequate enzymatic substitution the authors used repeated examinations of chymotrypsin in the faeces of 19 patients with insufficiency of external secretion (17 patients with chronic pancreatitis and two after duodenopancreatectomy on account of carcinoma of the pancreas). Adequate substitution (chymotrypsin > 6U/g faeces) is individual (1.8-7.2 g pancreatin--Kreon/day). The required dose may be higher in patients with chronic pancreatitis than in conditions following duodenopancreatectomy. When receiving adequate substitution treatment, the patients reported milder complaints, regression of pain and diarrhoea. In two patients with severe signs of malnutrition a satisfactory condition was achieved and their loss of body weight was arrested. The necessary dose of insulin in diabetic patients declined by 4-12 u/day. During treatment no adverse side-effects were found. PMID- 8506677 TI - [3 questions and answers from a long-term study of cardiovascular problems in the Most District]. AB - When processing data from the long-term follow-up of cardiovascular diseases in the Most district the author revealed: 1. In the course of 30 years the ratio of older subjects increased in the Most district (men above 60 years, women above 55 years) from 9.1% in 1961 to 17.3% in 1990; the ageing of the population in the Most district is more rapid than corresponds to average data from Czech Republic and the North Bohemian region. 2. In the course of 40 years (1950-1990) the rising trend of hospitalized morbidity on account of all cardiovascular diseases, ischaemic heart disease and myocardial infarction persists. 3. Analysis of the morbidity from cardiovascular diseases in 1989 in the Most district did not reveal any differences as compared with 1976. It was confirmed that the ratio of deaths from cardiovascular diseases rises with age. A limiting factor is also the necropsy rate, in particular as regards patients who did not die in hospital. Particularly alarming is the cardiovascular mortality in the group aged 40-69 years. PMID- 8506678 TI - [Thrombolytic therapy of acute myocardial infarct in a district hospital. Analysis of a group of patients treated with streptokinase]. AB - At the intensive care unit of the hospital and policlinical department in Zilina the authors treated between May 29, 1985 and Dec. 31, 1990, 87 patients with AIM by systemic administration of streptokinase which was injected after an average period of 2.5 hours following the onset of stenocardia. As to the selection of patients for thrombolysis and tactics of treatment, the authors proceeded according to an elaborated protocol. The upper borderline of the age range is not limited. Non-invasive markers of reperfusion of the heart muscle (regression of stenocardia, regression of ECG changes, reperfusion arrhythmias) were observed in 25-80% of the patients. There was only a small number of complications in the patients of the described group; they were not serious and did not call for therapeutic intervention. Thrombolytic treatment of AIM by streptokinase is a safe and effective method which can be successfully used also in intensive care units of district hospitals. PMID- 8506679 TI - [Anemia--the single symptom in celiac disease in adults]. AB - The authors describe the case of a 21-year-old female patient where for several months anaemia was the only symptom of subsequently diagnosed coeliac disease. They draw attention to the possibility of a monosymptomatic course of coeliac disease and discuss similar observations reported in the literature. PMID- 8506680 TI - [Therapy of refractory multiple myeloma. I. Monotherapy with glucocorticoids and combined cytostatic therapy]. AB - Treatment of refractory myeloma is still a problem. For patients where treatment with melphalan and prednisone had no effect, many therapeutic procedures were suggested and tested. Some were more, others less successful. In the first part of this review the author summarizes clinical studies which evaluate the importance of glucocorticoids and various combinations of cytostatics administered in this indication. He considers a continual four-day infusion of vincristine and adriamycin or mitoxantrone with large doses of glucocorticoids the most effective treatment. In the primarily resistant form glucocorticoids are the most important component of treatment. Finally the author presents a review of therapeutic patterns. In the second part of the paper the author will deal with the therapeutic results of large doses of cytostatics, interferon and discuss experience with transplantation of bone marrow in patients with myeloma. PMID- 8506681 TI - [The Saint Vincent Declaration--an invitation to participate in the care of diabetics. II]. PMID- 8506682 TI - [Circulatory changes in local and segmental use of shortwave diathermy]. AB - 6 healthy volunteers were examined for dose-effect relations, with a view to obtaining substantiated information for dosage in medical short-wave therapy. Venous occlusion plethysmography was used to measure total blood flow in the legs. So-called segmental treatment was checked, in addition to locally delimited high-frequency action. Low, medium, and high amounts of energy were therapeutically applied to the probands for 5, 10 and 20 minutes. Close correlations were found to exist between magnitude of blood flow, length of treatment and therapeutic intensity. The 20-minute variant proved to be the most effective application which differed from the literature according to which maximum intensification of blood flow was recorded at 10 minutes. The medium level of energy application was considered to be a highly favorable approach in terms of intensity. While higher doses usually provide the highest increase in blood flow, they may well cause discomfort. Blood flow remained increased after termination of therapy, usually for up to 60 minutes, in response to 20-minute medium-intensity short-wave treatment. Segmental high-frequency application likewise resulted in increased blood flow in both legs, though intensity values thus achieved were below results of locally delimited calf treatment. PMID- 8506683 TI - [Connective tissue massage]. AB - Connective tissue massage deals with the skin and the subcutaneous tissue. It focuses on definite regions of the body, assigned in segmental order to inner organ systems and structures of the locomotor system (spinal cord, joints, muscles). In case of acute disease, oedematous swelling of a generally soft tissue consistency can be observed in circumscribed areas. Persisting symptoms may result in induration of such tissues, associated with reduced rheology and epicritic pain if manipulated mechanically. Eventually, chronic conditions may progress to atrophy. The name "connective tissue massage" is based on the concept that corresponding physiological events take place in connective tissue structures and the segmentally associated organ. With regard to the pathophysiology of such zones, mechanisms which are comparable to sympathetic reflex dystrophy are discussed at present. Analysis of such changes has contributed to general diagnosis. Connective tissue massage is considered to be an important element of physiotherapy. The clinical data on the efficacy of connective tissue massage are reviewed. PMID- 8506684 TI - [Biosignals of dermal activity]. AB - Electrodermal activity (EDA) summarizes different electrophysiological dimensions of human skin. EDA is based on the activity of sweat glands and their innervation by the autonomic nervous system. EDA is used as indicator in the additional diagnostic assessment of patients in the fields of neurology and psychosomatic medicine. PMID- 8506685 TI - [Therapeutic muscle training]. AB - The needs and motives for a therapeutically oriented muscle training programme are quite varied. The attainment of the maximum possible muscle strength is not the decisive goal, but instead the achievement of motoric function permitting optimal performance during daily physical activities, supporting active participation in sports during leisure time, compensating for deficits in the musculo-skeletal system and counteracting a series of disturbances and limitations in general health. The following goals fall into the realm of a therapeutic muscle training programme: maintenance as well as improvement of muscle function--stabilization of the joints--increase in joint mobility- maintenance of the function of the total skeletal system--support of kinesthetics and body consciousness--promotion of emotional stability--prophylaxis of injury- improvement of the preconditions for total body training. From the above goals the following indications for a therapeutic muscle training programme can be deduced: maintenance of muscle strength and joint function during lack of physical activity and in advanced age--muscle building subsequent to periods of immobilization after injuries and surgery affecting the musculo-skeletal system- stabilization of the joint-muscle system in degenerative joint and spinal diseases, joint instability and hypermobility--treatment of muscular dysbalance, muscular insufficiency, postural abnormalities and weaknesses--mobilization of joints--prophylaxis and therapy of osteoporosis--calesthenics during pregnancy- therapy of urinary incontinence--adjuvant therapy for psychiatric disorders--part of a total body training regimen aimed at physical fitness and general health care. PMID- 8506686 TI - [Rehabilitation after stroke]. AB - Optimal rehabilitation should be available to every patient requiring such therapy as a basic right. Interdisciplinary cooperation is a prerequisite for the successful planning and carrying out of an individually tailored therapeutic regimen. The hemiplegic patient, in particular, requires a treatment schedule approached from different angles. If this is entirely lacking or only one-side, the expectations of the patient cannot be fulfilled. If current medical scientific concepts were universally put into practice, many cases of invalidity could be avoided. A systematic rehabilitation programme is certainly more cost effective than the long-term nursing care of an invalid. PMID- 8506687 TI - [Aortocoronary bypass operation or percutaneous transluminal coronary dilatation in patients over 70 years of age?]. AB - On account of improved outcome an increasing number of patients more than 70 years old have undergone aortocoronary bypass grafting or percutaneous transluminal coronary angioplasty over the past years. Elective coronary bypass surgery carries a risk in the range of 5 to 10% hospital mortality among this age group. However, excellent long term results are in favour of surgery in carefully selected patients. Major indications are patients with extended areas of myocardial ischemia due to left main stem or proximal triple vessel disease. Overall results of PTCA are, likewise, somewhat less satisfactory in geriatric patients than in younger ones. With careful selection of patients, however, morbidity and mortality of this intervention is low. Excellent indications for PTCA are short, concentric, non calcified single or multiple vessel lesions in symptomatic patients with good ventricular function. In patients with angina refractory to medical treatment who carry an increased risk of surgery, PTCA may be worthwhile even if the coronary morphology is less promising (type B or C lesion). PMID- 8506688 TI - [Aortic valve stenosis in the aged--replacement or dilatation?]. AB - In patients with severe symptomatic aortic stenosis the prognosis is very poor (1 year mortality rate 54%). Percutaneous transluminal aortic valvuloplasty shows a primary success rate of 86% and an in hospital mortality rate of 7%. However, within 6 to 12 months in almost all patients restenosis occurred. 23% of the patients died within this time range. 13 subjects with restenosis underwent redilatation or valve surgery. Aortic valve surgery is the treatment of choice in this setting. The method demonstrates also in elderly patients a relatively low early mortality rate and excellent long term results. Patients in NYHA stage IV, with severe coronary heart disease and with impaired left ventricular function (LVEF < 50%) show a 2.5 to 3.6 times increased early postoperative mortality rate. In these patients valvuloplasty may be performed as a palliative therapy or as a bridging procedure to aortic surgery. Aortic valvuloplasty may be indicated further in patients with reduced general conditions or severe secondary diseases. PMID- 8506689 TI - [Vascular diseases in the elderly]. AB - Obliterary artery diseases are not confined to the elderly but on the other hand a higher rate of acute symptoms in old age is observed because of multiple influences of the hemodynamics. Furthermore in old age only rarely a reversal of these symptoms takes place. In the underlying paper the several regions of the body which may be changed by the obliteration of the arteries are discussed. In addition the question of therapy will be taken into consideration. In general the therapeutic regimes will be the same as in younger age: muscle training of the legs, local lysis by catheter, late fibrinolysis, hemodilution, rheologically acting substances, along with an active interval training or a transluminal dilatation by catheter or a surgical intervention. Relevant concomitant diseases such as diabetes mellitus or hypertension and their relevance for obliterative vessel diseases will especially be stressed. PMID- 8506690 TI - [Therapy of cardiac arrhythmias in the aged]. AB - Epidemiologic studies showed an increased mortality and an increased risk for embolic events in atrial fibrillation. Two basic strategies for insult reduction were evolved beside the therapy of the underlying disease. Risk stratification is most important, because only a bad prognosis justifies an prophylactic anti arrhythmic therapy in an given benefit-risk relation. The pharmacological therapy has changed in respect to the non-pharmacological alternatives. PMID- 8506691 TI - [Arterial hypertension in elderly patients]. AB - The cardiovascular system changes in the elderly: reduced blood volume and cardiac output, diminished elastic properties of the arterial wall and increased peripheral resistance are to be expected. Arterial hypertension can be developed when these changing factors are not balanced, especially with the longer lasting of cardiovascular risk factors. Arterial hypertension can be found in nearly every second person older than 60 years living in industrial countries--it is common but nevertheless not normal in the elderly. Epidemiologic studies show the effectiveness of the antihypertensive drug therapy in the aged in diminishing cerebrovascular and coronary events and improving the quality of live. When elderly persons are treated with antihypertensive drugs, this therapy should be chosen in respect of target organ damage and accompanying health problems and with close monitoring of the antihypertensive response and tolerability. PMID- 8506692 TI - [Degenerative diseases of the joints and spine]. AB - A survey is given of the different kinds of osteoarthritis, how the diagnosis should be established, how the clinical examination should be performed; how information for the case history should be found out, and which supplementary findings (radiological laboratory) should be gathered. The therapeutic possibilities are discussed. PMID- 8506693 TI - [Radiology in degenerative diseases of the joints and spine]. AB - A differentiation is made between primary and secondary forms of osteoporosis. Furthermore the degeneration forms of rheumatism are discussed. PMID- 8506694 TI - [Rehabilitation in advanced age]. AB - Rehabilitation in the elderly is--apart from the question of social and economic advantages--of important significance. The various possibilities of treatment are discussed. PMID- 8506695 TI - [Balneotherapy in advanced age]. AB - For thousand of years cures have provided worthwhile above all upon the 3 social most important disorder groups: Degenerative joint disease, disorders of the heart and of vascular system and disease of the respiratory system. Its effectiveness and efficiency is proven. By the choice of a spa the unspecific and specific effects of the mineral springs should be considered. During the last years it was done very much in improving the quality of the therapy in spa and great efforts were made to integrate cures into rehabilitation programs. The old patient requires great care of all in the spa engaged. The atmosphere of the cure does not only soothe the physical troubles, it helps quite the old people to overcome the loneliness. PMID- 8506696 TI - Nutrition and fitness in health and disease. 2nd International Conference on Nutrition and Fitness. Athens, May 23-25, 1992. Proceedings. PMID- 8506697 TI - Declaration of Olympia on Nutrition and Fitness. May 26, 1992. PMID- 8506698 TI - Nutrition and fitness in the prophylaxis for age-related bone loss in women. PMID- 8506699 TI - In situ kinetics and ascorbic acid requirements. PMID- 8506700 TI - Are omega 3 fatty acids essential nutrients for mammals? PMID- 8506701 TI - Nutrition and fitness recommendations when science in transition. Vitamin and mineral supplementation: a case in point. PMID- 8506702 TI - Policies and programs in nutrition and physical fitness in Central and South America. PMID- 8506703 TI - Trends in physical fitness and nutrition in the USA. PMID- 8506704 TI - Policies and programs in nutrition and physical fitness in Greece. PMID- 8506705 TI - Nutrition and body build: a Kenyan review. PMID- 8506706 TI - Some recent policies and programs in nutrition and physical fitness in China. PMID- 8506707 TI - Coronary heart disease prevention, nutrition, physical exercise and genetics: rationale for aiming at the identification of subgroups at differing genetic risks. PMID- 8506708 TI - Can lifestyle changes reverse coronary heart disease? PMID- 8506709 TI - Fish and ischaemic heart disease. PMID- 8506710 TI - Nutrition and fitness in health and disease. Implementation and mobilization of resources. PMID- 8506711 TI - Genetics of obesity and its prevention. PMID- 8506712 TI - Obesity and its treatment by diet and exercise. PMID- 8506713 TI - Diet and exercise in the prevention of cardiovascular disease. PMID- 8506714 TI - Local and systemic factors in the pathogenesis of osteoporosis. PMID- 8506715 TI - [Is the bradycardic effect of tedisamil at the expense of the loss of the inotropic effect? A pressure-volume analysis with the conductance (volume) catheter technique in patients with coronary artery disease]. AB - To exclude or prove potential inotropic influences from tedisamil's bradycardiac effects, our hemodynamic evaluation in 13 patients (pat.) with coronary artery disease (CAD) included analyses of end-systolic pressure-volume relationships (ESPVR) after tedisamil, 0.3 mg/kg infusion at rest and during tachycardia induced by atrial pacing. Slope Emax [mm HG/ml] fell by 14% at rest (13 pat.) and by 10% during paced tachycardia (6/13 pat.) while loops of ESPVR tended to move rightward towards larger volumes (p > 0.05): all parameter changes indicated lack of significant inotropy loss with tedisamil. While mean heart rate decreased from 77.5 to 64.7 b/min and QTc duration increased by 14% (p < 0.05), filling pressure as well as dP/dtmin remained unchanged and vascular resistance rose by 30%. Parameters of LV-pump function (ejection fraction, stroke volume) decreased slightly (between 3 and 13%), while LV-volumes increased (end-diastolic by 6%, end-systolic by 23%). The respective parameter changes during paced tachycardia were comparable in tendency. CONCLUSION: Tedisamil's bradycardic effects are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion. Thus, tedisamil can be used safely in CAD. PMID- 8506716 TI - [Correlations between arrhythmias and left ventricular function at rest and during stress in patients with postinfarct aneurysm]. AB - The results (clinical, hemodynamic, and angiographic data) of 197 patients with left ventricular anterior wall aneurysm were evaluated at rest and during exercise (bicycle ergometer) 6 months after the acute infarction. Using the technique of digital subtraction angiography, left ventricular volumes were estimated after injection of contrast medium into the pulmonary artery and measuring of pulmonary artery pressure. In 136 patients a programmed right ventricular stimulation was performed additionally. The patients were divided into the following groups: patients with (VT+) and without (VT-) ventricular arrhythmias in history. Group VT- was subdivided in patients with positive (RV+) or negative (RV-) result of right ventricular stimulation. In group VT+ chamber volumes were greater and ejection fraction was smaller than in group VT-. At rest the results of subgroup RV+ were similar to group VT+, but during exercise similar to group RV-. These results show that left ventricular function at rest and during exercise is much more impaired in patients with spontaneous and by stimulation-induced arrhythmias than in patients without these arrhythmias. The conclusions for clinical practice of these findings are not yet clear, concerning, for example, the prophylactic use of antiarrhythmic measurements in patients without spontaneous but with induced arrhythmias. Further investigations (long-term follow-ups of these patients) will be necessary. PMID- 8506717 TI - [Anisotropic impulse conduction characteristics in chronic myocardial infarct. The importance for initiation and perpetuation of ventricular tachycardia]. AB - The underlying mechanism of most ventricular tachycardias in the setting of chronic myocardial infarction is reentrant excitation. At that time, the active membrane properties like upstroke velocity and amplitude of action potentials of muscle fibers surviving in the border zone of the infarction have returned nearly completely to normal. Anisotropic conduction characteristics, however, importantly contribute to the electrophysiologic properties of the epicardial and/or endocardial border zones in chronic myocardial infarction. In normal myocardial tissue with tight coupling between muscle fibers, conduction velocity is slower for impulses propagating transverse to fiber orientation compared to longitudinal to fiber orientation due to a higher effective axial resistivity ("uniform" anisotropy). With infarct healing, connective tissue invading into the epicardial border zone separates surviving muscle fiber bundles and thereby decreases cell-to-cell coupling ("non-uniform" anisotropy). In this setting, excitation waves propagate transverse to fiber orientation in an irregular sequence and conduction velocity in this direction is significantly reduced without occurrence of acute ischemia. Block of conduction waves propagating longitudinally to fiber orientation may lead to activation of the area distal to the block with long delay by very slow transverse wavefronts. This long delay allows fibers proximal to the line of block to regenerate excitability, and reentrant excitation may be initiated. The common pathway of figure-eight tachycardias preferentially orientates longitudinally to fiber orientation. Very slow conduction transverse to fiber orientation at the pivoting points of reentrant circuits may lead to the occurrence of excitable gaps. PMID- 8506718 TI - [Diagnostic and therapeutic problems in idiopathic prolonged QT syndrome. A case report]. AB - The case of a 36-year-old woman with suspected idiopathic long QT syndrome is reported. Diagnosis was made late after syncopal attacks and several episodes of resuscitation had occurred. Although therapy with a beta-blocking agent was initiated and a cardioverter/defibrillator was implanted, the patient died, due to a hydrocephalus internus resulting in cerebral damage. Diagnostic and therapeutic problems in idiopathic long QT syndrome are discussed. PMID- 8506719 TI - [Main branch stenosis after bypass operation. Indications for elective PTCA]. AB - The unprotected left main stenosis still represents one of the contraindications of PTCA; recently developed concepts using percutaneous bypass techniques have not changed this fact so far. However, following bypass grafting the procedure can be done with low risk and may improve prognosis in case of later bypass occlusion. This study should clarify whether a higher rate of bypass occlusion is caused by postsurgical left main PTCA. From October 1981 to January 1991 a left main stenosis was dilated in 41 patients, 2 weeks to 12 years (mean 3.5 years) after bypass grafting. To date, 17/65 venous bypass grafts were already occluded, and 72.4% of the patients suffered from typical angina. In 34/41 patients (82.9%) PTCA was successful, severe complications (death, emergency surgery or myocardial infarction) did not occur and clinical improvement was achieved in 80% of symptomatic patients. Four months later, 26/34 patients (76.5%) had angiographic follow-up. Fifteen restenoses were found and a second PTCA was performed in 9/15. None of the venous bypass grafts, open at the time of the first PTCA, was occluded at follow-up. In one case PTCA of the left main stenosis turned out to be life-saving 7 years later because an occlusion of RCA- and LCX-bypasses occurred and the LAD graft showed a subtotal thrombosis. It is concluded that PTCA of left main stenosis after bypass grafting is a safe procedure and does not lead to a higher rate of venous bypass occlusions. A prognostic indication seems to be justified. PMID- 8506720 TI - [Transvenous catheter occlusion of the patent foramen ovale in paradoxical embolism]. AB - Paradoxical emboli are assumed to be one cause for cerebral strokes of unknown etiology. These emboli usually cross from the right to the left heart via a patent foramen ovale. We describe the transvenous catheter occlusion as an alternative to surgical closure. There were no complications. The echocardiographic follow-up of 12 and 14 months demonstrated complete closure of the foramen ovale without recurrence of neurologic symptoms. PMID- 8506721 TI - [Complete visualization of a coronary fistula with drainage into the superior vena cava. Diagnostic benefit of biplane transesophageal echocardiography]. AB - A 36-year-old woman was referred because of a continuous cardiac murmur. Standard transthoracic two-dimensional echocardiography was normal. Using the transverse plane of biplane transesophageal echocardiography (TEE) a distinct dilatation of the proximal portion of the right coronary artery could be visualized. Morphology and the information from color-coded Doppler echocardiography were consistent with a coronary artery fistula. However, the exact course of the fistula and its drainage could not be seen. Only by using the longitudinal plane of biplane TEE its site of drainage into the vena cava superior could be demonstrated morphologically, as well as by color-coded Doppler imaging. PMID- 8506722 TI - [Imaging of a congenital coronary fistula using biplane transesophageal color coded echocardiography. A case report]. AB - A case report of a congenital coronary artery fistula between left main stem and pulmonary artery is presented. This fistula was not detectable by conventional transthoracic color-Doppler echocardiography. In contrast, precise localization of origin and site of drainage of this fistula could be demonstrated by biplane transesophageal color-Doppler echocardiography. Subsequent coronary angiography confirmed the echocardiographic findings. PMID- 8506723 TI - [Correlation between Doppler echocardiography and invasive determination of left ventricular hemodynamic valve parameters. A comparative study under routine conditions in a cardiology center]. AB - Simultaneously performed combined Doppler/catheter studies have shown excellent correlations regarding the comparison of invasively and non-invasively obtained valve gradients. To reflect daily clinical life the current study compared the valve parameters obtained by Doppler echocardiography to those obtained later by catheterization in all consecutive patients who underwent invasive procedure between October 1988 and December 1990. A total of 113 patients was included in the study, 76 with aortic and 37 with mitral stenosis. Regarding the mean aortic valve gradient the following correlations were obtained: all patients: r = .79, patients with an ejection fraction > 50% (n = 59): r = .81, patients with an ejection fraction < 50% (n = 17): r = .67, patients with additional aortic insufficiency (n = 21): r = .77. When the mean mitral valve gradient was compared the correlation was r = .71 for all patients and r = .44 when additional mitral regurgitation was present (n = 10). The comparison of the mitral valve orifice area (n = 30) showed a correlation of r = .58. CONCLUSION: Non-simultaneously performed combined Doppler/catheter studies in unselected patients do reflect daily clinical life, however, correlations are not as good as in corresponding simultaneously performed investigations, thus emphasizing the impact of the study conditions on the final results. PMID- 8506724 TI - [Diagnosis and therapy of coxitis fugax with special reference to the value of ultrasonographY-assisted diagnosis and hip joint puncture]. AB - Between 1984 to 1991 55 children (mean age 7.0 years) were observed with a painful effusion of the hip examined by ultrasound. Children with radiologically diagnosed hip diseases were excluded. In 47 cases we found a transient synovitis of the hip which started at an average interval of 4 days in mean before admission. All children were reexamined 6 weeks after the end of treatment sonographically and clinically, 4 of those revealing incipient Perthes diseases. The primary sonographic right/left difference in amount of effusion (mean) was 4.0 +/- 1.7 mm and after aspiration 1.5 +/- 1.4 mm with a significantly correlation with the amount of aspirated synovial fluid. The radiological findings for a diagnosis of an effusion of the hip were not reliable. Beside the diagnostic signs of the appearance of the aspirated fluid the sonographic assisted aspiration of the hip is an important treatment mode to reduce the intracapsular pressure and the pain of a hip effusion in children. PMID- 8506725 TI - [Changes in the sex life of female patients following intertrochanteric transposition osteotomy]. AB - Female patients planned for intertrochanteric osteotomy have to be advised in postoperative sexual impairment, besides surgical risks. Our investigation shows that the sexual experience was impaired postoperatively. Release from pain has to be contrasted to postoperative sexual problems. PMID- 8506726 TI - [Results of medullary space decompression in the early stage of so-called idiopathic femur head necrosis]. AB - The results of 47 cases of core decompression in 42 patients with stage I and stage II (according to Ficat) avascular necrosis of the femoral head who had been followed up for a minimum of two years were subjected to retrospective analysis. All these cases involved so-called "idiopathic necrosis" of the head of the femur including patients with risk factors (alcohol abuses, lipometabolic disorders and hyperuricemia). 87% of the 30 stage I hip joints showed no radiological signs of deterioration and could also be classified as clinically successful (average follow-up time 47 months (24-100 months). After an average follow-up period of 38 months (24-86 months), 41% of the 17 stage II hip joints had to be classified radiologically as failures. A good clinical or radiological result could be achieved in 59% of these cases. This procedure has proved to entail low risk, and can be recommended as the first choice of therapy at early stages of necrosis of the head of the femur. PMID- 8506727 TI - [Significance of arterial circulation disorders for the planning of hip prosthesis interventions]. AB - Between 1980 and 1990 a total of 17 patients who had undergone or had been selected for total hip replacement were treated in the Department of Surgery at Munster University. Angiographic studies performed because of persistent symptoms revealed circulatory disorders of the pelvic floor. Vascular surgery was necessary to eliminate symptoms in these patients. Postoperative complications in 3 patients following total hip replacement were also only eliminated by vascular surgery. In the present authors' view, failure to recognize preoperatively existing arterial circulation disorders can lead to misdiagnosis and severe postoperative complications. Every hip replacement operation should be preceded by a thorough clinical and--if doubt persists--an angiological examination. Documented arterial circulation disorders should be eliminated by vascular surgery prior to hip surgery. PMID- 8506728 TI - [Survival time of loosened cemented hip joint prosthesis]. AB - With the help of survival curves we analysed in 111 aseptically loosened endoprostheses of the hip the function of the implants. We found a mediate rate of 6.04 years for the total survival time. We discussed two peaks after 2 years and between the 5. and 8. year after the implantation. There was a reduction of the survival time in the upper age and in the right side of the implantation. The second implantation had a worse prognosis compared with the first implantation (medial rate of 2.38 to 6.6 years). Important causes for the loosening were an enlarged angle of the hip socket and a varus position of the stem. But the survival curves showed in connection with these factors no statistical significance. We found a reduction of the survival time in the cases with no complete boundary of the bone cement in the proximal part of the stem. PMID- 8506729 TI - [Clinical course of a late aseptically loosened PCA hip prosthesis shaft]. AB - The surface of the proximal part of a PCA endoprosthesis stem in total hip replacement is structured with small beads to provide good conditions for bone ingrowth. The distal part of the stem has a smooth surface. For the mechanical fixation concept, this means anchorage of the proximal part and free axial mobility of the distal part of the prosthesis. We present a clinical case in which bone remodeling processes finally led to complete loosening of the prosthesis. The described mechanism of loosening could be reconstructed by radiological findings, bone scan, two digital subtraction arthrographies of the hip and by evaluation of the fibrous tissue formation around the stem after explanation. In this case, after an initial period of no measureable bone reactions, distal endosteal bone and proximal radiolucent space developed without loss of contact with the prosthesis. Later, a mechanical interruption between the proximal part of the prosthesis and bone occurred. There was no loosening of the distal part of the prosthesis at this time. Despite remarkable hypertrophy of the distal femoral bone, eventually the distal part of the prosthesis loosened so that a revision arthroplasty had to be performed. The described mechanism of loosening has not be proven to pertain to all such prostheses. PMID- 8506730 TI - [Vascular injuries in acetabular implantation and acetabular replacement surgery- case report, literature review and anatomical study]. AB - Severe intraoperative bleeding during revision hip arthroplasty in one of our patients was the motive of the work reported here. A review of the literature and an anatomical cadaver study were carried out. The distance between the acetabular fossa and the intrapelvic blood vessels was measured in 15 specimens. The risk for the obturator artery is particularly high. The distance between this vessel and the acetabulum is 2 mm (1-5 mm) only. An account of previous complications and the vascular anatomy as pointed out in our report may help to prevent severe bleeding complications in hip surgery. PMID- 8506731 TI - [Quantitative analysis of autopsy femurs with cemented hip joint endoprosthesis]. AB - 48 retrieved femora with fixed cemented hip arthroplasties were sectioned horizontally. Bone sections of the whole cross-sectional area were studied morphometrically. No significant bone changes were found distal to the lesser trochanter, but frequently within the region of the calcar femoris. The interface between bone and cement mainly consists of a thin (< 25 microns) connective tissue layer, a "close bone/cement-contact" was found in 10 to 20%. Analysis of segmental loosening indicates that the implant should be fixed well along the whole stem. The bone alterations found are not very extensive and yield no explanation for aseptic loosening, but the frequently poor cement-fixation does. PMID- 8506732 TI - [Radiation therapy in the prevention of periarticular, heterotopic ossification following implantation of a total hip endoprosthesis]. AB - From June 1988 to January 1991 the efficacy of a low-dose (5 x 2 Gy) versus a high-dose (10 x 2 Gy, resp. 5 x 3,5 Gy) prophylactic postoperative radiotherapy was assessed in a prospective randomized trial. 60 patients at the highest risk for formation of heterotopic ossification (HO) were included in this study, i.e. patients that presented already HO in the ipsi- or contralateral hip at the time of surgery. After both irradiation regimen the incidence and severity of HO was significantly less than without prophylaxis; there was no significant difference (regarding the severity of HO, the hip score (16) and the hip mobility) between the two regimen. PMID- 8506733 TI - [Actinomycosis of the thigh muscles--a case report]. PMID- 8506734 TI - [Correlation of roentgen findings, intensity of pain and subjectively experienced impairment in gonarthrosis]. AB - At the Orthopedic Clinic of the Heinrich Heine University of Dusseldorf a clinical survey was carried out about patients with clinically obvious gonarthrosis. Wirth's rating was used to classify the x-ray state. The survey revealed the following correlations: Between the x-ray state according to Wirth and pain intensity measured by VAS scales exists a significant positive correlation (p < 0.001). Between the x-ray state according to Wirth and the individual clinical impairment measured by a modified LYSHOLM-SCORE exists a significant positive correlation (p < 0.001). The survey shows that the LYSHOLM SCORE modified by Kloos does reveal the subjective impairment caused by gonarthrosis. The survey points out that on the one hand the subjective impairment at Wirth's x-ray state IV is higher than at state III, but that on the other hand the pain-score is higher at state III than at state IV. PMID- 8506735 TI - [Effects of various load intensities in the framework of postoperative stationary endurance training on performance deficit of the quadriceps muscle of the thigh]. AB - The development of a muscular hypertrophy represents one of the most important purpose in a postoperative training. With the example of an isokinetic training the present study was meant to record if the choice of the load intensity is of importance in this connection. 36 patients with an anterior crucial ligament rupture, who were divided into three groups, underwent a stationary training for a period of four weeks. Thereby it could be proved that high intensity mainly influences the intramuscular coordination while the load intensity is far less relevant to the influence on a muscular cross-section. In this connection rather the total extent of practice time makes up the specific stimulus for a hypertrophy. PMID- 8506736 TI - [Intravenous administration of gadolinium DPTA in proton spin tomography of the knee joint]. AB - In a prospective study we evaluated the benefits of iv-application of gadolinium DPTA examining 25 patients with degenerative disease of the knee joint by MRI (1.0 Tesla). All patients were scanned with standard spin echo sequences (SE 500/20), short time inversion recovery sequences (STIR 1600/100), and FEDIF sequences (FEDIF 500/10). After gadolinium-DPTA application (0.1-0.35 mmol/kg BW) the patients were scanned with spin echo sequences (SE SE 500/20), and FEDIF sequences (FEDIF 500/10). After iv-Gadolinium the synovial membrane of joints with inflammation show significant increase of the signal. Due to this effect a differentiation between joint effusion and hypertrophic synovia is possible. Small areas of local synovitis not visible before the use of gadolinium can be documented. A differentiation between degenerative subchondral cysts and cysts due to an inflammatory process is possible. CLINICAL RELEVANCE: The use of iv application of gadolinium-DPTA in patients with degenerative joint disease seems to offer additional information. With iv-application all shortcomings of intraarticular use can be avoided. The differentiation between degenerative and inflammatory processes is possible. PMID- 8506737 TI - [Homologous cruciate ligament transplantation as intra-articular ligament replacement]. AB - A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after ACL repair. None of these procedures have been able to duplicate the fiber organization, attachment site anatomy, vascularity, or function of the ACL. 29 foxhounds received a deep frozen bone-ACL bone allograft and a ligament augmentation device (LAD). Biomechanical, microvascular, and histological changes were evaluated 3, 6 and 12 months following implantation. The maximum load of the allograft/LADs were 34.3% (387.2 N) after 3 months, 49.3% (556.6 N) after 6 months and 61.1% (689.8 N) after a year. The maximal load was 69.1% (780 N). In general, after 6 months the allografts showed a normal collagen orientation. The allografts demonstrated no evidence of infection or immune reaction. No bone ingrowth into the LAD was observed. Polarized light microscopy and PAS-staining showed that the new bone/ligament substance interface had intact fiber orientation at the area of ligament insertion. Microvascular examination using Spalteholtz-technique revealed neovascularization and the importance of infrapatellar fat pad for the nourishment of the ACL-allografts. PMID- 8506738 TI - [Pain as the main symptom in knee joint disorders]. AB - Knee pain as the leading symptom can show the way to the diagnosis. Transmission and character of pain indicates the different diagnosis. The theories of pain formation are shown and explain. The information given by the patient should not be the only reason for an active therapy. Also there should be some objective clinical statements in order to permit active therapy. The article shows the combination between pain and objective statements. PMID- 8506740 TI - "Tachycardiomyopathy". The most frequently unrecognized cause of heart failure? PMID- 8506739 TI - [Biomechanical principles in diarthroses and synarthroses. I: Basic concepts in diarthroses]. AB - The incongruity of the articulating surfaces is one of the main constructional characteristics of human joints. Unfortunately, this has virtually been neglected in studying of the mechanism of joints. Only in incongruent articulating surfaces does the force locking, which is permanently produced by gravity and/or compressively acting muscular forces (muscular tonus), engender mechanically stable states of balance of the connected limbs. From the incongruity one can conclude that the dimeric link chain represents the most simple constructional element of the human joints. They are force locked, constrained gear systems composed by dimeric link chains. In this context the overlapped dimeric link chain deserves special attention since it is the only mechanically stable device in the presence of compressive forces. We present fundamental terms and characteristics of the gear mechanisms of human joints. PMID- 8506741 TI - The use of intracoronary ultrasound for quantitative assessment of coronary artery lumen diameter and for on-line evaluation of angioplasty results. AB - The value of intracoronary ultrasound for quantitative assessment of minimal coronary arterial diameter and for on-line evaluation of balloon angioplasty result was studied in 42 patients undergoing single vessel coronary angioplasty. Measurement of minimal luminal diameter of 75 matched coronary arterial segments showed a significant correlation between both the ultrasound and angiographic method (r: 0.759; p < 0.001). Furthermore using intravascular ultrasound it was possible to classify the obtained coronary balloon angioplasty results. A preliminary correlation between ultrasound classification and the in-hospital acute rethrombosis as well as late restenosis was attempted in individual patients. CONCLUSIONS: 1) Clinical use of coronary ultrasound is feasible and safe in selected cases. 2) A significant correlation between intracoronary ultrasound and quantitative coronary angiography is demonstrated. 3) Using intracoronary ultrasound seems promising for evaluation of the postangioplasty result, and may finally lead to improved selection of the interventional strategy. PMID- 8506742 TI - Spectrum of cardiac involvement in systemic lupus erythematosus: echocardiographic, echo-Doppler observations and immunological investigation. AB - Cardiac involvement was noninvasively evaluated in 75 consecutive patients with systemic lupus erythematosus (SLE) by two-dimensional and Doppler echocardiography. In 50/75 patients anticardiolipin antibodies (aCL) were also investigated. Major endocardial damage, characterized by the simultaneous presence of both anatomical and functional valvular involvement (AFVI), was observed in three patients with valvular vegetations and in five patients with combined valvular stenosis and/or regurgitation. Nine patients showed only an anatomic valvular involvement (AVI), expressed by a thickening of one or more valvular leaflets, without echo-Doppler findings of valvular dysfunction. Occurrence of major valvular involvement appears to be correlated with both longer disease duration (9.8 +/- 5.6 yrs in AFVI group vs 5.7 +/- 5.6 yrs in the remaining SLE patients; p < 0.001) and IgG aCL (chi-square = 5.546; p < 0.05). Left ventricular systolic function, evaluated by two-dimensional echocardiographic ejection fraction, was preserved in all patients (EF: 60 +/- 5%). Left ventricular diastolic function, as expressed by echo-Doppler transmitral flow indices of left ventricular filling, was subclinically impaired in 23 patients: only disease duration was significantly longer in these patients (7.7 +/- 5.9 yrs vs 4.9 +/- 4.8 yrs; p < 0.05). Our study demonstrated that cardiac involvement is quite frequent in SLE patients: the disease duration affects both endocardial and myocardial involvement; the anticardiolipin antibodies appear to be related to endocardial but not to myocardial damage. PMID- 8506743 TI - Clinical aspects during long-term follow-up after DC shock ablation of the atrioventricular junction. A Belgian experience. AB - Ninety-three patients, who underwent DC shock ablation were reviewed over a mean follow-up period of 54 months (range 3 to 84 months). These patients (46 male and 47 female, mean age: 58 years) had failed an average of 3 drugs, and the duration of symptoms was more than 2 years. Paroxysmal atrial fibrillation or flutter was treated in 75 patients (80.6%); the remainder had supraventricular tachycardia or reciprocating tachycardia using an accessory pathway. One shock of 200 J was effective in producing third degree AV block in 40 patients (43%), while 2 or more shocks were used in another 53 patients (57%). Chronic complete heart block (CHB) was obtained in 85 patients (91%), modification of conduction was seen in 2 patients (2.1%), and failure to achieve an improvement in 6 patients (6.4). All the patients of the last group had received more than 4 shocks (200 to 400 J). However no significant difference between the amplitude of atrial and His electrograms could be shown between the CHB patients and those in whom conduction persisted. Over a mean follow-up of 54 months, 66 patients (72%) with successful ablation during the first 48 hours after the procedure remained in CHB. In 18 patients AV conduction resumed but they were all asymptomatic: 10 patients (10.8%) without antiarrhythmic therapy and 8 patients (8.6%) with medication. In conclusion, ablation of the AV junction is effective in more than 82% of patients. Most of the time long-term success can be predicted within 48 hours. However, due to the invasive character of DC shocks, this technique has been supplanted by the less aggressive radiofrequency method. PMID- 8506744 TI - Effect of acute blood pressure changes on signal averaged electrocardiogram. AB - An acute blood pressure elevation may cause ventricular ectopic rhythms, while its reduction may alleviate them. It is studied whether the blood pressure exerts some effect on parameters obtained by the signal averaged electrocardiogram. In 25 patients with either hypertension (8 cases) or ventricular ectopic rhythms (10 cases) or both (7 cases) the blood pressure was reduced by sodium nitroprusside (24 cases) and/or elevated with metaraminol (10 cases) and the signal averaging electrocardiogram was recorded under 2 or 3 pressure values on each patient. During the high pressure (193.6 +/- 20.1 mm Hg) the following differences were noted compared to the low pressure (77.4 +/- 15.2 less): longer QRS duration in all 25 patients (+9.92 +/- 10.51 ms, P < 0.001); longer low (< 40 microV) amplitude signals (LAS) in 18 patients (+6.94 +/- 10.93 ms, P < 0.005); lower root mean square voltage of the terminal 40 ms of the QRS in 22 patients (-15.73 +/- 21.60 microV, P < 0.005); and ventricular ectopic beat incidence higher in 8, lower in 1, and equal in 2 cases (with no arrhythmia in the other 14). The generally and focally reduced conduction, as suggested by the QRS and LAS prolongation, might contribute to the proarrhythmic effect of acute blood pressure elevation. PMID- 8506745 TI - A comparative study of the effect of coronary artery disease on ascending and abdominal aorta distensibility and pulse wave velocity. AB - The effect of coronary artery disease on aortic distensibility and pulse wave velocity was studied in 73 male normotensive patients, divided in two groups. Group A (n = 36) consisted of patients with normal coronaries and one-vessel disease and Group B (n = 37) of patients with two- and three-vessel disease. Distensibility (10(-6).cm2.dyne-1) was calculated from the equation: 2 x [(change in aortic diameter from systole to diastole/(diastolic aortic diameter) x (pulse pressure)]. Aortic diameters were measured with two-dimensional guided M-mode echocardiography. For ascending aorta distensibility calculations, pulse pressure (PP) measured at brachial artery with sphygmomanometry (BrPP) was employed. For abdominal aorta distensibility calculations, BrPP was corrected from the equation: corrected BrPP = 0.642 x BrPP + 42.54 (r = 0.9) obtained by comparing BrPP and abdominal aorta PP measured directly during cardiac catheterization. RESULTS: 1) Ascending and abdominal aorta distensibility were greater in Group A compared to Group B (2.732 +/- 0.92 vs 0.688 +/- 0.57, p < 0.0001 and 2.098 +/- 0.65 vs 0.871 +/- 0.64, p < 0.0001 respectively). Moreover, ascending was greater than abdominal aorta distensibility in Group A (p < 0.0001), while no significant difference between the two was observed in Group B and 2) Pulse wave velocity was inversely related to ascending and abdominal aorta distensibility (r = -0.56 and r = -0.5 respectively). Thus, high grade coronary atherosclerosis is associated with decreased distensibility and loss of elastic inhomogeneity of the aorta resulting in increased pulse wave velocity. PMID- 8506746 TI - Anti-Purkinje cells antibodies in two cases of paraneoplastic cerebellar degeneration. AB - The serum and CSF of two women with a severe subacute pancerebellar syndrome contained high titers of antibodies directed against antigens present in the perikaryon of Purkinje cells. In Western blots performed on human Purkinje cells extracts these antibodies reacted with two groups of proteins the molecular weights of which were estimated to 34-38 and 62 kilodaltons (anti-Yo antibodies). Complementary investigations revealed a tubar adenocarcinoma in the first case, an ovarian carcinoma in the second. The tubar tumoral cells also contained the protein of the highest molecular weight. Compared to the serum, the CSF contained a higher proportion of anti-Yo antibodies per mg IgG, and a fraction of the latter was likely synthesized intrathecally. These antibodies may be involved in the almost total disappearance of the Purkinje cells, as observed at autopsy of both cases. PMID- 8506747 TI - Electrophysiological study (VEP, BAEP) in HIV-1 seropositive patients with and without AIDS. AB - One hundred-twenty nine HIV-1 seropositive patients (39 females, 90 males) were studied by means of pattern visual evoked potential (VEP) and brainstem auditory evoked potential (BAEP) recording. Utilizing the criteria of the Centers for Disease Control the patients were clinically defined and then subdivided into four groups: group A included patients of category II (n:11); group B patients of category III (n:29); group C patients of category IVa and IVc2 (n:55) and group D patients belonging to the other subgroups of category IV (n:34). EP were altered in 26.35% of the entire group with a marked prevalence of BAEP alterations (21.7%) rather than of VEP (4.65%). A considerable amount of BAEP abnormalities (24.13%) were found in patients with persistent generalized lymphadenopathy (group B). A significant increase of BAEP mean interpeak latencies were observed in group B, C, D patients when compared with those of the control group. On the whole, EP were altered in 20.65% of the neurologically asymptomatic patients. EP alterations may precede any clinical manifestation and can be found during the earlier phases of HIV-1 infection. PMID- 8506748 TI - Assessment of left ventricular diastolic function in chronic mitral regurgitation by Doppler left ventricular inflow and left ventricular ultrastructural morphometry. AB - Doppler left ventricular (LV) inflow is reportedly affected by LV diastolic properties. We evaluated 48 subjects consisting of 27 patients with chronic mitral regurgitation (MR) and 21 patients with noncardiac disorders who received echocardiographic examinations. The deceleration rate divided by diastolic dimension (DR/Dd) derived from Doppler early diastolic LV inflow was correlated with the peak diastolic velocity divided by diastolic dimension (peak DV/Dd), a conventional index of LV diastolic function derived from the M-mode echocardiogram in the 48 patients, regardless of the presence of normal sinus rhythm or atrial fibrillation. LV diastolic function was then estimated by comparing perioperative echocardiographic examination and LV micro-and ultrastructural findings of biopsy specimens from 12 patients with MR who received mitral valve replacement. Fiber diameter, volume fraction of interstitial fibrosis (int. % Fib), and volume fractions of three intracellular components; the myofibrils (% MF), the sarcoplasmic reticulum (% SR) and the mitochondria (% MT), were measured in LV transmural biopsy specimens. DR/Dd was significantly correlated with peak DV/Dd before and after operation. Peak DV/Dd and DR/Dd were inversely correlated with int. % Fib and % SR, and were positively correlated with % MF. We subdivided the 12 MR patients according to their postoperative DR/Dd values as "recovered", and "non-recovered" based on their postoperative LV diastolic function. % MF was significantly lower in the 'non recovered' group. Thus, DR/Dd can serve as an index of LV diastolic function. A decrease in % MF may inhibit the recovery of postoperative LV diastolic function. PMID- 8506749 TI - Beneficial effect of EPC-K1 on the survival of warm ischemic damaged graft in rat cardiac transplantation. AB - A newly introduced compound, EPC-K1, represents a phosphate diester linkage of vitamin E and vitamin C. The effect of EPC-K1 on the reperfusion injury was evaluated in a heterotopic cardiac transplantation model using syngenic combination rats. Prior to the warm ischemia, 12mg EPC-K1/kg was administered intravenously to donor rats. After 15 min of warm ischemic time, hearts were harvested and perfused with 4 degrees C saline. After completion of the transplantation, recipient rats were also treated with intravenous 12 mg EPC K1/kg, before reperfusion. Saline was used instead of EPC-K1 for both donors and recipients in the control group. On the 7th post-transplantation day, graft survival was 7 out of 8 in EPC-K1 group, versus 1 out of 9 in the control group (p < 0.001). Thiobarbituric acid-reactive substance levels in the recipient serum, three hours after reperfusion, were significantly limited, in the group in which EPC-K1 was administered only to donors. But it was not possible to clarify whether the effect of EPC-K1 is primarily at the donor or recipient levels at this time. These results indicate that EPC-K1 may reduce reperfusion injury after cardiac transplantation. This beneficial effect may be mediated by the hydroxyl radical scavenging properties of EPC-K1. PMID- 8506750 TI - Second malignant neoplasms after treatment for osteosarcoma: a report of three cases. AB - We report second malignant neoplasms which developed between 7 and 19 years after treatment in 3 pediatric patients with osteosarcoma. Two patients had been treated with only surgery, and another patient had been treated with a combination of surgery with chemotherapy and radiation therapy for primary lesions. Pediatric patients with osteosarcoma, in particular, require careful long-term follow-up to monitor not only metastases but also development of second malignant neoplasms. PMID- 8506751 TI - Occlusion of a postoperative rectoabdominocutaneous fistula with fibrin clot: a case report. AB - A 56 year-old rectal cancer patient who developed a chronic rectoabdominocutaneous fistula postoperatively was treated with fibrin clot, and the fistula healed completely. Occlusion of chronic postoperative fistulas with fibrin clot appears to be a useful technique. PMID- 8506752 TI - Overexpression of interleukin-2 receptor alpha mRNA in pulmonary lymphocytes of lung cancer patients associated with interstitial pulmonary shadow. AB - The activity of pulmonary lymphocytes was evaluated by the detection of interleukin-2 (IL-2) receptor alpha mRNA expression in lung cancer patients associated with diffuse interstitial shadow on roentgenograms of their lungs. Reverse transcription coupled with the polymerase chain reaction was used to detect mRNA expression. In 5 of 6 patients, IL-2R alpha mRNA expression was increased in pulmonary lymphocytes compared with 4 normal controls. The expression in this mRNA in peripheral blood lymphocytes was almost undetectable in either normal controls or these patients. These results suggest that pulmonary lymphocytes in patients with lung cancer associated with diffuse interstitial shadows are activated and may promote the inflammatory process generating pulmonary fibrosis. PMID- 8506753 TI - Immunotherapy by a slow delivery system of interleukin-2 in mice models. AB - A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pellet (IL-2 mp), was developed by fusing IL-2 into a needle shaped collagen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL 2 in the serum became undetectable by 6h after a subcutaneous injection of 1 x 10(6) unit of IL-2 in phosphate-buffered saline (PBS). In contrast, after a single subcutaneous injection of IL-2 mp containing the same amount of IL-2, the concentration of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK activity and generation of IL-2 activated killer cells were observed in the spleen from day 1--day 3 after a single subcutaneous injection of IL-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adoptive immunotherapy by a single subcutaneous injection of IL-2 mp followed by intravenous injections of in vitro cultured IL-2 activated killer cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506754 TI - Formation of Charcot-Leyden crystals by human basophils in sputum and peripheral blood. AB - To confirm the formation of Charcot-Leyden crystals (CLC) in basophils, we observed basophils in sputum and peripheral blood. Sealed slide and suspension culture methods were used to observe the process of CLC formation in peripheral blood basophils and eosinophils under electron microscopy. CLC formation was observed in basophils and eosinophils, and was found to be augmented by sealed slide method. A temperature of 4 degrees C was better than 37 degrees C for promoting the formation of crystals. There was no correlation between the degranulation of these cells and the formation of CLC after stimulation with anti IgE or anti-IgG antibodies. CLC were initially detected in the cytoplasmic granules of basophils where they continued to enlarge. No CLC were identified in mast cells under any conditions studied. These findings confirm that CLC in sputum are not exclusive to eosinophils and that CLC appear to be present in basophil-rich sites under the cell damage. PMID- 8506755 TI - What factors are involved in the knowledge necessary for the self-management of diabetic patients? AB - The aim of this study is to obtain data for improving a training program for patients with diabetes mellitus. One hundred eighty-seven patients with non insulin dependent diabetes mellitus were tested with 20 questions about their knowledge for self-management of diabetes mellitus. Then to draw out factors in their personal backgrounds relating to their correct answers, multiple regression analyses were conducted. As a result, four factors showed significant differences in the following order: Educational careers > ages > duration of disease > socioeconomic strata. The results of the present study have shown for the first time, that these four factors closely concern patients to acquire the necessary knowledge for their self-management of the disease. In addition, this study has raised some fundamental problems regarding the training program for patients: how education should be given to patients. PMID- 8506756 TI - Ultrastructure and X-ray microanalysis of epiphyseal growth cartilage of femoral head processed by rapid-freezing and freeze-substitution. AB - Epiphyseal growth cartilage of the femoral head obtained from Wistar rats was investigated after fixation by a rapid-freezing and freeze-substitution. Liquid helium was used in order to achieve a fast cooling rate without ice-crystal damage during the rapid freezing. Use of the rapid-freezing and freeze substitution procedure provided better ultrastructural preservation of the chondrocyte than conventional chemical fixation methods. This procedure allowed a more reliable approach to electron probe analysis. X-ray microanalysis of the specimens confirmed that calcium is not detected in the initial matrix vesicles as a result of the freezing process. The results suggest that calcium release from precipitates occurs in the free state without any detectable formation of hydroxyapatite at the initial stage of calcification and that calcium is not tightly bound to the matrix vesicles. PMID- 8506757 TI - The in vitro perifused rat ovary: III. Interrelationship of the follicular and stromal compartments on steroid release. AB - The preovulatory ovary is composed of two primary tissue components, stroma and follicles. To assess the role of these tissue compartments in ovarian steroidogenesis, stromal tissue, follicular tissue, and a mixture of both tissues from pregnant mare serum gonadotropin (PMSG)-treated, prepubertal rats were perifused simultaneously for 8 h. The basal level of estradiol secretion by stromal tissue was lower (24 +/- 3 pg/mg/30 min), than that secreted by follicles (64 +/- 5.6 pg/mg/30 min, n = 6; p < 0.05). On the other hand, the mean basal levels of progesterone and testosterone secreted by stromal tissue (252 +/- 14 pg/mg/30 min and 162 +/- 18 pg/mg/30 min, respectively) were greater than those secreted by follicular tissue (84 +/- 3 pg/mg/30 min and 81 +/- 4 pg/mg/30 min, respectively). When stromal and follicular tissue were combined the secretion of progesterone, testosterone and estradiol was intermediate to that of the separate tissues. Under gonadotropin stimulation (human menopausal gonadotropins plus follicle stimulating hormone), the follicular tissue secreted greater amounts of steroids than did the stromal tissue, or stromal plus follicular tissue. When stromal tissue and follicular tissue were combined, the levels of basal progesterone and testosterone secreted by both tissues were significantly lower than those of stromal tissue alone. However, the reduction in follicular estradiol secretion induced by stromal tissue under basal conditions, was in large part overcome during gonadotropin perifusion. These observations suggest that locally produced factors may play an inhibitory, paracrine role in the regulation of ovarian steroidogenesis. PMID- 8506758 TI - The in vitro perifused rat ovary: V. The significance of the follicle stimulating hormone and luteinizing hormone ratio on steroid release. AB - In these studies, an in vitro perifusion model was used to compare stimulation of ovarian tissue with either human menopausal gonadotropin (hMG), which is an equal mixture of luteinizing hormone (LH) and follicle stimulating hormone (FSH), or with hMG plus added human FSH. Eight-hour perifusion studies were conducted on either whole, or dissected clusters of follicles from pregnant mare serum gonadotropin (PMSG)-treated rats. In the two groups, similar stimulatory protocols were used, consisting of a ramp stimulation over 60 min with either hMG (0-8 mIU/ml) or hMG plus FSH (0-8 mIU/ml hMG + 0-8 mIU/ml FSH), followed by hourly pulse stimulation with hMG (8-18 mIU/ml) or hMG plus FSH (8-18 mIU/ml hMG + 8-18 mIU/ml FSH), respectively. In the whole ovaries, no differences were detected in progesterone, testosterone, or estradiol secretion. However, in the cluster of follicles, an elevated hFSH/hMG ratio resulted in a significantly higher secretion of progesterone, testosterone and estradiol (n = 8; p < 0.05) than the steroids secreted by follicles perifused with hMG alone. In conclusion, an elevated FSH: LH ratio led to greater steroidogenic responses by the perifused cluster of follicles, but not by the whole ovary. PMID- 8506759 TI - Estradiol, progesterone and androstenedione content of follicular fluids in 'empty follicles'. AB - In an in vitro fertilization (IVF) and embryo transfer program with human menopausal gonadotropin/human chorionic gonadotropin treatment no oocytes were recovered in 18 out of 788 cycles. Estradiol (E2), progesterone (P) and androstenedione contents of 27 follicles obtained from five of the 18 patients were radioimmunologically measured and P:E2 ratio calculated. Control values of 20 follicles were obtained from four of these five patients in subsequent IVF cycles. A total of 17 oocytes were harvested. Estradiol, progesterone and androstenedione mean +/- SEM values (nmol/l) were, respectively, 4246 +/- 1484, 3751 +/- 1768 and 1920 +/- 641 in the failed cycles and 2504 +/- 908, 13,678 +/- 4749 and 509 +/- 87 in the successful ones. P:E2 ratios were 0.88 +/- 1.03 and 5.67 +/- 1.70, respectively. The differences in these levels of progesterone, androstenedione and the ratios of P:E2 were significant (p < 0.01). It is concluded that the probable cause of 'empty follicles' is inappropriate luteinization and they are not characteristic for a given patient or for stimulation with human menopausal gonadotropin/human chorionic gonadotropin. PMID- 8506761 TI - The concomitant release of androstenedione with cortisol and luteinizing hormone pulsatile releases distinguishes adrenal from ovarian hyperandrogenism. AB - Androstenedione secretory characteristics and its possible temporal correlation with luteinizing hormone (LH) and/or cortisol, intended as the markers of, respectively, ovarian stimulation and adrenal secretion, were evaluated in 24 patients affected by clinical hyperandrogenism. A pulsatility test was carried out for 8 h, with sampling every 10 min, and LH, cortisol and androstenedione profiles were determined by radioimmunoassay. Time series were analyzed with the computer program DETECT and with a program for specific concordance estimation. A distinct episodic release of LH, cortisol and androstenedione was observed in all patients (6.9 +/- 0.8, 5.2 +/- 0.6 and 5.5 +/- 1 peaks/8 h, respectively). When specific concordance was tested between LH and androstenedione, and between cortisol and androstenedione, two distinct groups of patients could be identified. Group A (n = 13) showed a significant specific concordance (SC) index only for LH and androstenedione while group B (n = 11) showed a significant SC also for cortisol and androstenedione, thus demonstrating a consistent adrenal participation in the androstenedione secretion in these patients. In addition, specific differences were observed on androstenedione secretory profiles of group B which showed a significant (p < 0.05) decrease of androstenedione plasma concentrations emulating cortisol behavior. No such observation was noted in group A, whose androstenedione plasma levels did not show any reduction. In conclusion, our data support the use of circulating androstenedione, LH and cortisol plasma levels and copulsatile assessment to distinguish the presence of two populations of hyperandrogenic patients: one whose hyperandrostenedionemia is mainly due to ovarian secretion (group A) and one which showed a hyperactivation of the adrenal gland (group B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506760 TI - Elevated serum inhibin levels and suppressed luteinizing hormone surge in young patients stimulated with gonadotropins. AB - The physiological role of inhibin and its relation to other sex hormones (estradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH)) has been investigated during gonadotropin-stimulated cycles of 38 in vitro fertilization-embryo transfer/gamete intrafallopian transfer (IVF ET/GIFT) patients. Human menopausal gonadotropin (hMG) was given from day 3 of the cycle until 1 day before ovulation induction with human chorionic gonadotropin (hCG). Blood samples were taken twice daily and hormone measurements performed by radioimmunoassay or enzyme immunoassay. Patients were divided into two groups: Group A comprised patients < 35 years of age (n = 20) and Group B included patients > or = 35 years of age (n = 18). The pregnancy rate was significantly higher in Group A. During the follicular phase, serum inhibin level rose gradually in both groups but the values were higher in Group A (significantly between days -2 and 0). During the early luteal phase serum inhibin concentrations were similar in both groups. Estradiol pattern did not differ in the two groups. Estradiol pattern did not differ in the two groups. Whilst serum estradiol level did not increase significantly after day 0, serum inhibin concentration reached its peak value 1 day later, on day +1. Serum progesterone was higher in Group A between days +1 and +4 (significantly on days +1, +3 and +4). Serum FSH increased slowly in both groups and did not correlate with serum inhibin concentration. Basal LH concentrations were similar between days -6 and -2 in both groups. Around the time of ovulation induction (day -1, 0 and +1) serum LH was lower in Group A (significantly on day 0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506762 TI - Ovarian electrocautery: responders versus non-responders. AB - The endocrine and biophysical attributes of 29 patients with polycystic ovarian disease (PCOD) were examined before and after laparoscopic ovarian electrocautery to establish the criteria which determined their clinical response. Patients with high luteinizing hormone (LH) levels (> 12 IU/l) had a better response than patients with lower LH values but a high LH: follicle stimulating hormone (FSH) ratio (> or = 2:1). However, the body mass index, ovarian volume or pretreatment testosterone values were not helpful in predicting the clinical outcome. Both responders (n = 22) and non-responders (n = 7) showed a decline in LH and testosterone and an increase in FSH 6-h mean values, following 15-min blood sampling 1 month after surgery, compared to the corresponding pretreatment levels. The magnitude of change was significantly higher for LH (p < 0.01) in responders but there was no difference in the corresponding values of the other hormones between the two groups (p > 0.05). Accordingly, unsupplemented ovarian electrocautery is better reserved for the treatment of patients with PCOD and high LH values. Four of the 17 patients who had second-look diagnostic laparoscopy showed minimal to mild pelvic adhesions and all patients had patent Fallopian tubes. The performance of a second-look diagnostic laparoscopy is not indicated as a routine procedure in all cases following surgery. PMID- 8506763 TI - Clinical and endocrine effects of laser vaporization in patients with polycystic ovarian disease. AB - Responses to laparoscopic ovarian laser vaporization were studied in 17 anovulatory patients with clomiphene citrate-resistant polycystic ovarian disease (PCOD). Ovulatory cycles were obtained in 14 patients (82%). A total of 11 patients (65%) conceived within 1-8 months. Measurements of basal serum hormone levels before and after the procedure in 12 patients revealed a significant decline in testosterone, dihydrotestosterone and androstenedione. In addition, luteinizing hormone (LH) levels decreased, but not significantly. On the other hand estradiol levels slightly increased and a surge in luteal progesterone levels was noted. Serum levels of sex hormone binding globulin, prolactin, dehydroepiandrosterone (DHEA) sulfate, 17-OH-progesterone and follicle stimulating hormone (FSH) remained unchanged. These results suggest that ovarian laser vaporization is very useful when clomiphene citrate fails in PCOD, and has no risk of ovarian hyperstimulation syndrome or multiple gestation, which is frequently observed in ovulation induction with drugs. Most of the endocrine abnormalities associated with PCOD are corrected by the laser procedure. PMID- 8506764 TI - An open study of luteinizing hormone releasing hormone agonists in infertile women with uterine fibroids. AB - Twenty infertile women with fibroids were treated with luteinizing hormone releasing hormone agonists (LHRHa) to investigate if the use of these drugs, both with and without myomectomy, was effective in contributing to pregnancy in these women. All women had fibroids as their sole cause for infertility. Seven women conceived within 1 year of myomectomy or LHRHa treatment alone without myomectomy. The overall pregnancy rate was 36% and the postmyomectomy pregnancy rate was 50%. Initial fibroid size and extent of fibroid shrinkage on LHRHa therapy made no difference to the subsequent pregnancy rate. We also found no significant interaction between the number of fibroids present and the effect of myomectomy on the proportion of pregnancies. We conclude that the fertility enhancing value of myomectomy in otherwise idiopathic infertility is confirmed, and that the use of LHRHa premyomectomy in infertile women needs to be investigated in randomized controlled trials to assess its value as a preoperative therapy. PMID- 8506765 TI - Correct timing of administration of diuretic agents for the treatment of ovarian hyperstimulation syndrome. PMID- 8506766 TI - Endothelin-1 receptors on the human placenta and fetal membranes: evidence for different binding properties in pre-eclamptic pregnancies. AB - Densities and affinities of tissue protein receptor sites for endothelin-1 in placental and fetal membranes of six preeclamptic and 16 normotensive women in the 36-41st week of gestation were determined by the use of a binding assay with [125I]endothelin-1. The mean maximal density of receptor sites (Bmax) was significantly higher in the placentas of the pre-eclamptic than of the normotensive women (905 +/- 107 vs. 539 +/- 140 fmol/mg protein, p < 0.0001). No differences were found between the two groups with respect to the mean affinity (Kd) of placental receptors, or the mean Bmax and the mean Kd of fetal chorionic samples. In the normotensive group, there were no differences in mean placental Bmax values or in mean Kd values between women who went into spontaneous labor (whether delivered vaginally or abdominally) and those who were electively operated on prior to labor onset. No binding sites were detected in the fetal amniotic membranes of any of the women. Our results suggest that an increase in the maximal density of receptor sites to endothelin-1 in the placenta may play a role in the pathophysiology of pre-eclampsia by contributing to the placental insufficiency that characterizes this disorder. PMID- 8506767 TI - The in vitro perifused rat ovary: IV. Modulation of ovarian steroid secretion by insulin. AB - Insulin has been implicated as a regulatory factor in ovarian steroidogenesis. To assess this issue, we examined the role of insulin on steroid secretion by whole ovaries from pregnant mare serum gonadotropin (PMSG)-pretreated rats, using an in vitro perifusion ovarian model. Three concentrations of insulin were perifused in the absence and presence of gonadotropin pulse-stimulation. Bioactive insulin concentrations after perifusion of ovarian tissue were 4, 40 and 400 mIU/ml. In the absence of gonadotropin-pulse stimulation, acute perifusion with insulin had no effect on ovarian steroid secretion. During stimulation with luteinizing hormone (LH) plus follicle stimulating hormone (FSH), insulin significantly decreased the secretion of testosterone and estradiol but increased the output of progesterone. This effect was only evident after 180 min perifusion and with the highest concentration of insulin. We conclude that acute elevation of insulin concentration has no effect on basal ovarian secretion of progesterone, testosterone, or estradiol in gonadotropin-pretreated rats. However, insulin has a moderate effect on steroid secretion in ovaries exposed to LH/FSH pulsatile stimulation, resulting in a decrease in estradiol and testosterone release, and stimulation of progesterone secretion. PMID- 8506768 TI - [Historic review of the treatment of urethral stenosis]. AB - The present paper reviews the various therapeutical schemes with which urologists have approached the difficult problem of urethral stenosis. It pictures a brief history of one particular chapter of Urology that has troubled men since the dawn of mankind and of which many questions still remain unresolved. PMID- 8506769 TI - [Ambulatory ureteral lithotripsy with "Modulith SL-20"]. AB - Analysis of our experience in 'in situ' ambulatory shockwave extracorporeal lithofragmentation of ureteral stones in 104 patients seen in the Lithotrity Unit, Urology Service, Fundacion "Jimenez Diaz". Using Modulith SL 20, a third generation lithotripter, 'in situ' disintegration was achieved in 82.69% of cases, 51.92% of which were fragmented in a single lithotrity session. As a first choice, no ureteral handling was used in any of the patients prior to lithotrity. In 9.62% of patients it was necessary to place a 'double J' by-pass catheter, due to the disease presenting with a septic picture. The patient's position was either dorsal or ventral decubitus depending on the lithiatic site, while location and focusing of the stones was done radiologically. All patients were treated ambulatory without hospitalization. Only 18% was given oral or i.v. anaesthesia. Fursemide 40 mg was administered to all patients shortly before starting the session. Each patient received an average of 3,200 shockwaves per session (14-18 Kv, average 16 Kv). Haematuria was the single and modest side effect that happened during the 24 hours following lithofragmentation in 30% of patients, while 20% reported slight discomfort at the time of eliminating the gritted stones. We conclude stating that 'in situ' shockwave extracorporeal lithotrity of ureteral stones with Modulith SL 20 allows for elective disintegration of ureteral stones in whatever location they are found, due to the patient's easy positioning. The simple location and focusing of ureteral stones has allowed us to treat and solve some cases of ureteral lithiasis at the precise moment of the nephritic colic painful emergency, thus speeding up and facilitating the resolution of the condition. Our results and our strategy imply a new change of direction in the management of these lithiasis, as opposed to the well established and historical doctrines in existence regarding stones with ureteral location. PMID- 8506770 TI - [Antimicrobial prophylaxis in urethrocystoscopy. Comparative study]. AB - Instrumentation of lower urinary tract is a predisposing factor for the development of urinary infection. Incidence of infective complications following urethrocystoscopy has been evaluated in a multicenter, prospective, comparative and randomized study in 2,284 patients, who had a previous negative urine culture. Patients were randomized into two groups: one to be used as control and the other one to received antimicrobial prophylaxis prior to instrumentation (ceftriazone, 1 gr intramuscular). Clinical and microbiological responses were evaluated at 48-72 hours and 4 weeks after cystoscopy. Symptomatic bacteriuria was observed in 10.2% of patients in the control group and in 2.5% in the prophylaxis group (p < 0.000); asymptomatic bacteriuria in 3.02% and 1.52% (p > 0.05) and irritative syndrome with sterile urine in 2.93% and 2.60% (p > 0.05), respectively. Thus, the use of prophylaxis reduced the incidence of infective complications in these patients. PMID- 8506771 TI - [Surgical wound infection in renal transplant recipients]. AB - Between 1980 and 1991, 504 transplantations were performed in our hospital. All patients received pre-surgical therapy with antibiotics. The total incidence of surgical wound infection was 15 cases (3%). After reviewing all parameters that could have been involved in the development of these infections, it become apparent that diabetes mellitus, more than one transplant in the same patient, development of haematoma in the wound and presence of urinary fistulae were statistically significant (p < 0.05). On the other hand, the use of the different immunosuppressive regimes (azathioprin and cyclosporin) and acute tubular necrosis showed no statistical significance (p > 0.05); also, no relationship was found between infection and acute graft rejection. PMID- 8506772 TI - [The urologist's language: a survey on symptoms]. AB - The definition of urologic symptoms varies depending on the source. Some symptoms are particularly vague and their clinical usefulness is doubtful. A survey was sent to 500 spanish urologists, asking about terminology and normality limits. There were 17 items, most of them as multiple choice questions, and all of them with the possibility of an open answer. The response rate, two months after the mailing was 12% (60 physicians). The variability of the answers was high for most of the items. In most questions over half of the respondents (between 50 and 70%, depending on the question) agreed, whereas the rest gave different answers. The free answers given were also different. This discrepancy affected all of the questions. The low response rate can be attributed to the scare tradition of this kind of survey in our country. The disparity in the definitions urges a unification of them, or at least that authors explain what they understand when they mention any symptom or syndrome. PMID- 8506773 TI - [Does transurethral resection cause metastatic dissemination of hormone treated prostatic cancer?]. AB - The evolution of non-metastatic prostate cancer treated with hormonal therapy does not appear to be affected by the performance of a transurethral resection (TUR) as a measure to expedite the common urinary tract. Of 82 patients followed for an interval ranging from 6 months to 15 years, 3 of 45 patients (6.7%) undergoing RUT experienced metastatic dissemination, while the same happened in 2 of 37 (5.4%) patients who did not undergo RUT, p being NS. The group of patients requiring RUT, however, experienced higher local progression rates, 22.2% vs 5.4%, a situation not ascribable to the RUT procedure but to the fact that such surgery was selectively indicated in neoplasias with larger tumoral mass. PMID- 8506774 TI - [Endometrial carcinoma of the prostate. Report of a case]. AB - Endometrial Carcinoma is an uncommon intraductal prostatic tumour, the origin (either from prostatic epithelium or Muellerian) and management (traditional hormonal therapy vs. progestagens) of which has been the subject of vigorous debate. Currently and with the help of the immunohistochemical techniques its origin has finally been confirmed as being prostatic, thus justifying the use of the traditional hormonal therapy applied in prostate acinous carcinoma. The paper contributes one case of Endometrial Carcinoma confirmed by immunohistochemical techniques, as well as a review of the main landmarks in the study of these tumours. PMID- 8506775 TI - [Inverted papilloma of the urethra]. AB - The inverted papilloma of the urethra is an exceptional entity. It occurs as a smooth surface, sessile tumour located in the prostatic urethra. Microscopically, it is lined with transitional epithelium which is projected inside the tumour, creating strands of cells with normal characteristics. All cases reported up to now have occurred in men aged between 49 and 79. None of the cases had additional urothelial injuries associated. Contribution of a new case of inverted papilloma of the prostatic urethra in a 52-year old male. Transurethral resection of the tumour was the procedure chosen. Evolution was good and no relapse nor further urothelial injuries were observed at the controls carried out over an 8-year follow-up period. PMID- 8506776 TI - [Renal leiomyosarcoma]. AB - Presentation of one case of a large, rapidly growing and highly aggressive renal leiomyosarcoma. The diagnostic and therapeutical possibilities of this infrequent tumour are analyzed. PMID- 8506777 TI - [Testicular microcirculation in rats measured with laser-Doppler flowmetry]. AB - Study carried out in 50 male Wistar rats distributed into 5 groups: baseline and at 2, 4, 8 and 24 hours after subcutaneous injection of Human Chorionic Gonadotropin, 100 IU. It was observed that testicular microcirculatory flow shows a rhythmical fluctuating pattern (5-10 fluctuations per minute), which becomes continuous at 4 hours but recovers at 24 hours. At the same time, there is an increased volume of testicular interstitial fluid that peaks at 8 hours, and returns to baseline levels at 24 hours. Serum testosterone values increase with HCG injection, reaching a peak at 4 hours (25.9 mg/ml), to return to nearly baseline levels at 24 hours (5.04 mg/ml). Disappearance of the rhythmical microcirculatory pattern, and the increase of interstitial fluid volume do not appear to be mediated by testosterone, since the raise in hormone levels, occurred after HCG administration, preceded the observed microcirculatory changes. PMID- 8506778 TI - [Paraurethral cyst of the Skene's gland]. AB - Presentation of an uncommon case of paraurethral cyst of Skene's gland in a 29 year old female patient. Analysis of the anatomical, clinical and therapeutical aspects of these gland's pathological mechanisms with regard to this case. PMID- 8506779 TI - [Laparoscopic bladder diverticulectomy]. PMID- 8506780 TI - Behavioral treatment of addictions. PMID- 8506781 TI - Psychological profile of college students who use smokeless tobacco. AB - The purpose of this study was to develop a psychological profile of smokeless tobacco users. We surveyed 1991 college students regarding their use of tobacco products. Twenty-one percent of the white males used smokeless tobacco compared to only 10.4% of blacks, 5.4% of Hispanics, and 5.4% of others, primarily Asians. Although the prevalence of smokeless tobacco use reported by Asians was relatively low, their rate of reported smoking was over twice as high as any other ethnic group, 43.6%. The most important reasons for beginning to use smokeless tobacco were to "see if I would enjoy it," "most friends used it," and "try something new." The personality profile of the smokeless tobacco users differed from that of smokers and non-users of tobacco. College students with the highest probability of being a smokeless tobacco user were white males who scored higher in extraversion and neuroticism but lower on state anxiety than non-users. PMID- 8506782 TI - Alcohol and social anxiety in women and men: pharmacological and expectancy effects. AB - A replication study was conducted to determine pharmacological and expectancy effects of alcohol on self-reported anxiety in a social interaction situation. Thirty-two male and thirty-two female social drinkers were randomly assigned to four conditions in a 2 x 2 factorial balanced placebo design, controlling for drink content and expectations. Results show that in women alcohol expectancy reduced self-reported anxiety, whereas in men there was no significant effect of expectancy. Alcohol consumption reduced anxiety in both men and women. Controlling for beliefs increased some of the effects we found. We conclude that although cognitive factors do mediate the effects of alcohol on self-reported anxiety, this influence seems to be different for men and women and the role of pharmacological factors might be more crucial. PMID- 8506783 TI - Relationship among social and intrapersonal risk, alcohol expectancies, and alcohol usage among early adolescents. AB - Numerous studies have shown that adolescents' expectancies about the effects of alcohol influence usage. Expectancies are described as mediators between social influences (such as peer and parental influences) and alcohol use. The present study examined the relationship between social risk factors (peer influence and parental approval), intrapersonal risk factors (tolerance of deviance and sensation seeking), alcohol expectancies, and alcohol usage in a cohort of seventh graders. It was hypothesized that social risk factors affected alcohol usage indirectly through expectancies, while intrapersonal risk factors influenced usage both directly and indirectly. Structural modeling was used to examine the hypothesized relationships between these four constructs. Results indicated that the hypothesis that expectancies mediate social influences was not supported, and that social influences exerted a direct influence on usage independent of expectancies. Results suggested that the view that expectancies mediate social risk factors may need modification. Suggestions for future research in this area include the need to examine the relationships among these constructs longitudinally and with adolescents over a broader age range. PMID- 8506784 TI - A proposed revision of the Fagerstrom Tolerance Questionnaire. AB - This article presents the results of initial testing of a revised version of the Fagerstrom Tolerance Questionnaire (TQ). Revisions were designed to improve the psychometric properties of the TQ. Four diverse samples of cigarette smokers completed the 10-item Revised Tolerance Questionnaire (RTQ), and responses were subjected to psychometric and factor analyses. Substantial improvement in internal consistency was obtained as compared to prior studies of the TQ. In addition, the results of factor analysis indicate that a substantial amount of covariation among the 10 items can be accounted for by a single common factor. Thus, unlike the TQ, the RTQ appears to be measuring a unidimensional construct. Also, preliminary data on temporal stability are positive. With respect to validity, the RTQ correlated moderately with the TQ and outperformed the TQ in predicting expired alveolar carbon monoxide. Finally, suggestions for further establishing the validity of the RTQ are offered. PMID- 8506785 TI - Bulimia and interpersonal relationships: an extension of a longitudinal study. AB - We examined changes in bulimia in female college students and changes in the relationship between bulimia and satisfaction with interpersonal relationships. We extended data collected from a 19-month time period in a previous study to a 31-month time period. Bulimics, subclinical bulimics, and normals showed a leveling off of the previous decline in bulimic symptoms assessed at the 19-month testing. There were strong negative correlations between the Bulimia Test and ratings of satisfaction with male interpersonal relationships, but the correlations were not significant for satisfaction with female relationships. PMID- 8506786 TI - The effects and use of maintenance newsletters in a smoking cessation intervention. AB - This article evaluates the effects and use of adjuncts to a televised smoking cessation program, based on the American Lung Association's "Freedom From Smoking in 20 Days." Subjects were randomized to maintenance and control conditions. The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline. The maintenance condition did not increase cessation at any wave of interviewing, assessed by multiple point or point prevalence of abstinence. Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage. Rates of use of the telephone hotline were low. The newsletters appear to be useful to smokers who are predisposed to use written materials. PMID- 8506787 TI - The social context of drinking scales: construct validation and relationship to indicants of abuse in an adolescent population. AB - A series of items that measure the social context of alcohol consumption among adolescents was administered in a questionnaire survey to over 1,300 high school students. Emerging from a factor analysis were five factors which suggested that drinking occurs in the following social contexts: drinking for social facilitation where adults are not present, drinking at school or during school related activities, drinking for stress control, drinking for conformity or to be part of a group, and drinking under parental supervision at home. Scales based on these factors appeared to be reliable, free from social desirability bias, and able to discriminate problem drinkers from nonproblem drinkers. The most important of these factors was drinking for social facilitation that is not restrained by the presence of adults. These findings reinforce the validity of examining the social context of drinking (which involves situational as well as motivational reasons for drinking) to uncover important etiological contributors of alcohol abuse in an adolescent population. PMID- 8506788 TI - Effect expectancies for cocaine intoxication: initial vs. descendent phases. AB - This study examined the association between proximal vs. distal effect expectancies for cocaine consumption in a college student population with (N = 26) and without (N = 69) cocaine experience. Participants completed the Cocaine Effect Expectancy Questionnaire-Likert (CEEQL) and were asked to respond to each item twice: first, their belief about that specific effect during the initial phase of cocaine intoxication; and second, in relation to their belief about that effect during the descendent period. Positive and negative scales were scored for each subject. Positive expectancies were not associated between the two time points, while negative expectancies were. Users reported significantly less negative expected effects of cocaine, while nonusers and users held similar beliefs about the positive effects of cocaine. This latter effect was replicated in an independent sample (N = 140). PMID- 8506789 TI - The effects of calories and taste on habituation of the human salivary response. AB - The present study examined the effects of calories on salivary habituation. The rate of habituation to lemon taste was studied over 10 trials in 24 normal weight, nondieting, 18-35-year-old females. Between each of the trials, half the subjects ate low calorie, lemon gelatin, total Kcal = 32, and the others ate high calorie, lemon gelatin, total Kcal = 320. A dishabituating, novel chocolate taste was presented on trial 11 and recovery of salivation was assessed by presenting lemon flavor on trial 12. Subjective ratings were taken before and after salivary habituation for hunger levels and hedonics for lemon taste. Results show that high- and low-calorie groups both habituated to the repeated presentation of lemon taste, but with no significant differences as a function of calories in salivation volume, rate of habituation, hunger level decreases, and hedonic decreases. Subjects in both groups perceived equal caloric intake. These results suggest that salivary habituation may be affected more by the sensory characteristics of the food than by differences in caloric intake. The generalization of these data to the development of satiety are discussed. PMID- 8506790 TI - One-year evaluation of three smoking cessation interventions administered by general practitioners. AB - Three smoking cessation interventions designed for use by general practitioners (GPs) within the routine consultation were evaluated in a field setting using 26 GPs throughout metropolitan Sydney. A total of 450 smoking patients were allocated to either Structured Behavioral Change with nicotine gum (Group SBCN), Structured Behavioral Change without nicotine gum (Group SBC), or GP advice with nicotine gum (Group AN). Although significant differences in the percentage of abstainers were observed between Groups SBCN and SBC three weeks after treatment (39% vs. 26%), the point prevalence abstinence rate for patients at 12 months declined to 19, 18, and 12% for Groups SBCN, SBC, and AN, respectively. Continuous abstinence to the end of the 12-month period was 9% for Groups SBCN and SBC, and 6% for Group AN. Forty-eight percent of the 450 patients made an attempt to stop smoking, and 89% reduced their cigarette consumption at some point during the study. Examination of 132 self-selecting patients who fully participated in the three interventions and attended all scheduled visits, revealed significantly larger proportions of abstainers within Groups SBCN (34%) and SBC (33%) than in Group AN (15%) at the 12-month follow-up. PMID- 8506791 TI - Excessive exercise and weight preoccupation in women. AB - A group of adult women (n = 351) were assessed on a number of psychological, behavioral, and body composition measures including weight preoccupation and leisure-time physical activity participation. The purpose of the study was twofold. It was intended (a) to investigate whether excessive exercises have specific characteristics in common other than that they exercise a great deal and (b) to identify the degree of relationship between exercising and weight preoccupation, and the extent to which those classified as excessive on either dimension have psychological characteristics in common. Results indicated that excessive exercisers reported greater body satisfaction and body focus, were less emotionally reactive (neurotic), and more extraverted than nonexercisers. Although some researchers have reported psychological similarities between excessive exercisers and women with eating disturbances, our data do not entirely support that point of view. While excessive exercise was associated with a decrease in body dissatisfaction and was negatively related to neuroticism, weight preoccupation was associated with an increase in body dissatisfaction and was positively related to neuroticism. However, one characteristic that both excessive groups shared, and that significantly differentiated them from their nonexcessive counterparts, was their high level of body focus. These findings led us to test the body focus x neuroticism interaction on both exercise participation and weight preoccupation. Results indicated a highly significant interaction on weight preoccupation. However, only the two main effects were significantly related to exercise. PMID- 8506792 TI - Drug abuse prevention for high-risk African American children and their families: a review and model program. AB - In this article we are specifically concerned with the familial and socioeconomic factors that contribute to the exceedingly high prevalence rates of drug abuse in African-American children. In addition to detailing the impact of drug abuse in African-American children and their families, we consider how this critical health problem can be prevented using existing knowledge and strategies known to mental health professionals. A model program entitled Project for a Substance Abuse-Free Environment (SAFE) is outlined. Its objectives are to implement: (a) a broad-spectrum family intervention to empower disadvantaged and high-risk families in their communities: (b) a competency-based skills intervention to increase resilience and decrease drug use and other maladaptive behaviors in at risk children; (c) alternative activities that will promote self-efficacy, achievement, and self-esteem; (d) a culturally-relevant evaluation plan that includes both formative (process) and summative (outcome) evaluation; (e) a comprehensive approach for assessing project impact; (e) systematic procedures for enhancing the maintenance and generalization of gains in participating children and families. PMID- 8506793 TI - [Clinical experience of endopyelotomy]. AB - From July 1986, percutaneous endopyelotomy was performed on a total of 12 patients (13 kidneys) including 8 males and 4 females with ureteropelvic junction (UPJ) obstruction. Of the 13 kidneys, 9 had primary UPJ obstruction and 4 had secondary UPJ obstruction. A rigid urethrotome (cold knife) was employed in 12 cases and a flexible electorotome (hot knife) in one case. A stent ureteral catheter was placed for 3 to 31 weeks after the procedure. The outcome was evaluated by radiography and urodynamic examinations. A successful outcome was obtained in 8 of 9 kidneys with primary UPJ obstruction and in 1 of 4 kidneys with secondary UPJ obstruction. These findings suggest that percutaneous endopyelotomy is useful in the treatment of primary UPJ obstruction. PMID- 8506794 TI - [Clinical studies of stage D2 prostatic cancer]. AB - Between 1981 to 1991, 126 patients were diagnosed with prostatic cancer from histological reports. Stage D2 prostatic cancer was confirmed in 38 of these cases at the time of the initial diagnosis (group alpha). Of 38 patients in group alpha, 13 had recurrence of disease after a good response to the initial treatment, 19 had no recurrence after the treatment and the other 6 patients showed no response to the initial treatment for prostatic cancer. Seven patients showed progression of the disease to stage D2 during the observation period (group beta). These forty-five patients with stage D2 prostatic cancer were analyzed. Poorly differentiated adenocarcinoma was the most frequently observed histological grade, followed by moderately differentiated. The grade of the extent of the disease (EOD) on bone scan was classified as EOD I in 26, EOD II in 13 and EOD III in 4, with no significant differences in the survival rate found among these groups. The sensitivity rate of prostate specific antigen was higher than that of other serum tumor markers. Twenty-three patients died during the observation period. 18 of the 23 died of prostatic cancer. PMID- 8506795 TI - [Testicular function after spermatic cord torsion]. AB - Semen quality and endocrine parameters after spermatic cord torsion were investigated. Of 24 patients evaluated following spermatic cord torsion 12 were treated with bilateral orchiopexy (orchiopexy group), and 12 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). The average sperm density and the average total sperm count in the orchiectomy group were significantly lower than those in the orchiopexy group (p < 0.05, p < 0.05, respectively). The mean serum follicle stimulating hormone level in the orchiectomy group was significantly higher than that in the orchiopexy group (p < 0.05). These findings suggest a significant decrease in testicular function in the orchiectomy group. All the patients in the orchiopexy group demonstrated a normal semen quality and endocrine parameters during followup. Four of the 8 patients in the orchiectomy group whose duration of followup was more than two years still demonstrated oligozoospermia (< 20 x 10(6)/ml, one of 4 was azoospermia). The average age at operation of these four patients with abnormal semen quality was significantly higher than that of the other 4 patients with normal semen quality (p < 0.05), whereas no significant difference in duration of torsion preceding surgical therapy was observed between these two groups. These findings suggest that subsequent semen quality is likely to remain within normal limits with early surgical treatment by bilateral orchiopexy. Ipsilateral orchiectomy in the younger generation seems to result in less damage of the contralateral testis than in the older generation. PMID- 8506796 TI - [Lymphangiomyomatosis involving the kidney: a case report]. AB - A 58-year-old female was admitted with a chief complaint of gross hematuria. A diagnosis of carcinoma of the left kidney with lymphnode metastasis was made on the basis of computerized tomography and angiography. Left nephrectomy and lymphnode dissection were performed. Histological examination revealed lymphangiomyoma, and the final clinical diagnosis was changed to lymphangiomyomatosis with pulmonary, retroperitoneal, and left renal lesions. Lymphangiomyomatosis with renal lesions is extremely rare, and differentiation from renal carcinoma is important, though difficult. PMID- 8506797 TI - [A case of retroperitoneal fibrosis with special emphasis on diagnosis using the magnetic resonance imaging]. AB - A case of idiopathic retroperitoneal fibrosis (RF) is reported. MRI showed a low signal intensity on T1 and heterogeneous signal intensity on T2-predominant image. Although this could be demonstrated either in malignant RF or early stage of non-malignant RF, differentiation from malignancy was made from the quick response to steroid therapy. PMID- 8506798 TI - [Ureteral stump metastasis from renal cell carcinoma: a case report]. AB - A case of ureteral metastasis from renal cell carcinoma is reported. A 71-year old man who had received radical nephrectomy for left renal cell carcinoma, G1 and about two years earlier presented with asymptomatic macrohematuria. He had received interferon therapy and surgical treatments for bone metastasis two times after the operation. Cystoscopic examination revealed bleeding from the left residual ureter but CT scan showed no abnormal findings. Left ureterectomy and partial cystectomy was performed and a small finger tip-sized tumor was found at 13.5 cm above the ureteral orifice. Pathological examination showed metastatic renal cell carcinoma, G1 > G2. Histologically and clinically, this tumor seemed to have metastasized by a hematological pathway. Seventeen cases of ureteral metastasis of renal cell carcinoma have been reported previously in the Japanese literature. PMID- 8506799 TI - [A case report of markedly effective recombinant interferon therapy in residual tumor of renal cell carcinoma]. AB - A 53-year-old man complaining of pain in his right upper abdomen was diagnosed as suffering from right renal cell carcinoma with tumor thrombus. Right nephrectomy was performed but curative operation was not possible because of the adhesion of the tumor to psoas muscle. The residual tumor spread to the second lumbar vertebra and the patient complained of lumbago. The tumor continued to grow and the patient suffered from paraplegia even after the administration of natural interferon for 32 weeks. The administration of 9 x 10(6) units of recombinant interferon alfa 2a three times a week, however, resulted in an 86.5% reduction of the tumor after 13 weeks and the patient between able to walk. The PR continued for 17 months. PMID- 8506800 TI - [Three cases of cystic testicular disease: simple cyst of the testis, cyst of the tunica alubuginea and mature cystic teratoma]. AB - We experienced three cases of cystic testicular disease including simple cyst of the testis, cyst of the tunica alubuginea and mature cystic teratoma. Cystic testicular diseases have been considered rare, but increasing usage of ultrasound in the diagnosis of scrotal diseases has made them more common. Ultrasonography seemed to be useful to distinguish nonneoplastic testicular cysts (simple cyst of the testis, cyst of the tunica alubuginea) from cystic lesions of solid testicular tumors. PMID- 8506802 TI - [Clinical experience with extracorporeal shock wave lithotripsy using Dornier MFL 5000-(U) for urinary stone]. AB - Our hospital recently installed one of the newest types of extracorporeal shock wave lithotripters, a Dornier MFL 5000-(U). We conducted preliminary clinical trials with the apparatus from April to June 1991. In this report we discuss our experience with the first 40 patients (52 stones) treated in a total of 52 extracorporeal shock wave lithotripsy (ESWL) sessions. Follow up observation was conducted for three months. Except in one case, invasive anesthesia was not used. A double J-catheter was inserted in 13 cases, a ureteral catheter in 7 cases, and percutaneous nephrolithotripsy (PNL) was used after ESWL in one case. After one month of follow-up, 27 patients (67.5%) were completely free from stone fragments, while at 3 months after treatment, 34 patients (85.0%) were free from stone fragments. No serious complications were observed after ESWL. We concluded that the Dornier MFL-5000-(U) apparatus is effective for renal and ureteral stones and generates no serious complications. PMID- 8506801 TI - [Two cases of male infertility with pathological dilatation of ejaculatory duct]. AB - Two cases of male infertility with pathological dilatation of ejaculatory duct are reported. In both cases, the dilatated wall of the ejaculatory duct was incised at the vermontanum with a cold knife endoscopically. After the incision, the findings of semen analysis of one case improved markedly and his wife became pregnant. In another case, semen analysis was not improved. Transurethral incision seemed to be a useful modality for the treatment of pathological dilatation of ejaculatory duct. PMID- 8506803 TI - [Intracavernous injection of lipo prostaglandin E1 for the diagnosis of impotence: a comparative study with prostaglandin E1-CD]. AB - Intracavernous injection of 20 micrograms prostaglandin E1-CD (PGE1-CD, 8 cases), 5 micrograms lipo prostaglandin E1 (Lipo PG-E1, 8 cases) or 10 micrograms Lipo PGE1 (9 cases) was performed in patients with functional impotence in order to comparatively analyze the diagnostic efficacy of these drugs. Full erection was observed in all patients who received intracavernous injection of 20 micrograms PGE1-CD or 10 micrograms Lipo PGE1. However, full erection was observed in 4 out of 8 patients administered 5 micrograms Lipo PGE1. RigiScan was used on all patients, and latency until erection (achievement of maximum rigidity of the base) after injection, maximum rigidity of the penile tip and base and circumferential expansion rate of the penile tip and base were measured. With regard to these RigiScan data and duration of erection, there were no significant differences among the 3 groups. There were no severe side effects in any of the patients. These findings indicate that 10 micrograms Lipo PGE1 and 20 micrograms PGE1-CD have similar effects and that Lipo PGE1 may be an effective drug for the diagnosis and treatment of impotence. PMID- 8506804 TI - [Clinical study on efficacy of a Foley catheter coated with silver-protein in prevention of urinary tract infections]. AB - We evaluated the clinical efficacy and safety of a Foley catheter coated with silver-protein (ProAg catheter) in the prevention of catheter-associated bacteriuria. ProAg catheter significantly reduced the incidence of extraluminal catheter-associated bacteriuria compared with usual latex Foley catheter although it did not inhibit intraluminal bacteriuria. There was no difference between ProAg catheter and latex catheter in the side effects such as urethral discharge, catheter-associated pain and allergic reaction. The ProAg catheter may be useful as an indwelling urethral catheter. PMID- 8506805 TI - AAOF Endowment Fund. PMID- 8506806 TI - Angle versus Case. PMID- 8506807 TI - Angle versus Case. PMID- 8506808 TI - Angle versus Case. PMID- 8506809 TI - Angle versus Case. PMID- 8506810 TI - Treatment of a high angle case with idiopathic bilateral mandibular hypoplasia, condylar and fossa erosion, and chronic rheumatoid arthritis. PMID- 8506811 TI - Cervical and oblique headgear: a comparison of treatment effects. PMID- 8506812 TI - The headgear effect of the Herbst appliance: a cephalometric long-term study. AB - The short- and long-term effects of the Herbst appliance on the maxillary complex were evaluated in 45 patients who had Class II malocclusions. The patients were followed for 6.4 years (5 to 10 years) after treatment. Lateral cephalograms from before and after 7 months of treatment, 6 months, and 6.4 years after treatment were analyzed. During Herbst treatment the upper molars were distalized in 96% of the subjects (maximum 4.5 mm), and the upper molars were intruded in 69% of the subjects (maximum 3.5 mm). The maxillary occlusal plane was opened in 82% of the subjects (maximum 7.5 degrees). Sagittal maxillary jaw base position seemed unaffected by therapy. A downward tipping of the palatal plane was noted in 47% of the subjects (maximum 2 degrees). During the first 6 months after therapy most of the treatment changes reverted. During the following 5.9 years after treatment, normal growth developmental changes prevailed: the upper molars moved mesially, and the teeth extruded, the occlusal plane closed, the maxilla grew anteriorly, and the palatal plane tipped downward. In conclusion the Herbst appliance exhibited a pronounced high-pull headgear effect on the maxillary complex. Without proper retention, however, the effect seemed to be of a temporary nature. PMID- 8506813 TI - The effect of facial growth, attrition, and age on the distance from the cementoenamel junction to the alveolar bone crest in the deciduous dentition. AB - The aim of this study was to describe the distances from the cementoenamel junction to the alveolar bone crest (CEJ-ABC) in the deciduous dentition and to relate them to age, facial, and tooth structure in 72 dry human skulls. Age correlated significantly with anterior face height (AntFH), the distance from condyle to gnathion (Co-Gn), lateral face height (LatFH), molar anatomic crown (MAC), and molar space (MS). The CEJ-ABC per skull and for the molars correlated with age, LatFH, AntFH, Co-Gn, MS, and MAC. The CEJ-ABC for the canines and the incisors correlated with age, LatFH, AntFH, and Co-GN. Multiple regression analysis on the effect of age, AntFH, LatFH, Co-Gn, and MAC on the CEJ-ABC distances indicated that they account for 36.3% of the CEJ-ABC distance per skull, 68.8% for the molars, 34.3% for the canines, and 44.2% for the incisors. The effect of each variable while controlling for the others indicated that age, LatFH, and MAC had a significant effect on the CEJ-ABC of the molars, whereas only age had a significant effect on the CEJ-ABC of the canines and incisors. These results indicate that there is a site-specific effect of facial growth and attrition on the CEJ-ABC distances in the deciduous dentition. PMID- 8506814 TI - Rhinometry and open-mouth posture in young children. AB - A biracial sample of 348 elementary school children who were in the first grade were assessed for open-mouth posture (OMP) in the natural environment. In addition, rhinometry was performed on 296 of the children. Means were computed for percent OMP and cross-sectional nasal airway. Results indicated that, in general, these children exhibited relatively high rates of OMP. Boys displayed significantly greater OMP than girls, and black children showed significantly larger cross-sectional nasal areas than white children. A significant correlation between OMP and nasal area only was evident for children exhibiting OMP during more than 80% of the observation intervals. The implications of the findings were discussed. PMID- 8506815 TI - Location of the mandibular center of autorotation in maxillary impaction surgery. AB - Controversy exists about the location of the center of autorotation of the mandible after maxillary impaction surgery. This investigation focuses on the problems associated with locating that center of autorotation and identifies factors that can increase the probability of accurately identifying its location for predicting surgical outcomes. The reliability of the Rouleaux technique for calculating the centers of rotation is established and is shown to be acceptable, as long as the landmarks used for determining the center are properly selected, and the magnitude of the rotation required is sufficient. The location of the centers of autorotation of the mandibles after maxillary impaction surgery for 46 patients was used to investigate the errors associated with landmark selection and amounts of rotation. Although there is much variation in its location, the center does not lie within the body of the condyle but instead lies away from the condyle. Guidelines for maximizing the reliability of predicting surgical outcomes on the basis of autorotation of the mandible after maxillary impaction surgery are given. PMID- 8506816 TI - Scanning electron microscope (SEM) evaluation of clinical failures of single crystal ceramic brackets. AB - The objective of this work was to perform failure analysis on Starfire brackets that failed in clinical use. The failed brackets were examined with a scanning electron microscope (SEM) to obtain micrographs at magnifications of 20, 50, 100, and other magnifications, whenever necessary. With the aid of the micrographs, the fracture origin and the probable defect that initiated the fracture were identified. The percentages of failure origins for each area of the bracket were arch wire slot 36.0%, tie wing slot 22.0%, undetermined 11.0%, saddle 9.0%, impact 9.0%, during removal 7.5%, and parting area 5.5%. By observing the micrographs pertaining to each field failure, the primary causes of failure were internal defects 47.5%, machining interference 42.5%, and undetermined 10.0%. PMID- 8506817 TI - An inventory of United States and Canadian growth record sets: preliminary report. AB - A listing and description of longitudinal craniofacial growth record sets currently extant on the North American continent is provided. An argument is made for the preservation of these resources and for the generation of a pooled or shared image base of duplicate craniofacial physical records. This is a preliminary report and is assumed to be incomplete. In an effort to improve our accuracy and completeness, we invite corrections and additions. PMID- 8506818 TI - Hardcore, softcore or fringe? PMID- 8506819 TI - Fragile X syndrome and failure to thrive. PMID- 8506820 TI - Gay teenagers. PMID- 8506821 TI - Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis. PMID- 8506822 TI - Patients with familial short stature: correction and clarification. PMID- 8506823 TI - Acute pediatric warfarin (Coumadin) ingestion: toxic effects despite early treatment. PMID- 8506824 TI - Prevention of perinatal transmission of hepatitis B virus infection. PMID- 8506825 TI - Acquired immunodeficiency syndrome: no time for kudos. PMID- 8506826 TI - Streptococcus viridans--not! PMID- 8506827 TI - Treatment of visceral leishmaniasis with meglumine and allopurinol. PMID- 8506828 TI - Are we educating a medical professional who cares? PMID- 8506829 TI - A 2- to 3-year outcome after bronchiolitis. AB - OBJECTIVE: To determine the risk factors and short-term outcome until 3 years of age for subsequent wheezing in children with early childhood bronchiolitis or pneumonia. DESIGN: Prospective follow-up of a patient group. SETTING: University hospital providing primary care for all pediatric patients of a defined area. PATIENTS: One hundred twenty-seven children under 2 years of age hospitalized owing to wheezing (n = 83) or pneumonia (n = 44) during 12 months in 1981 to 1982. One hundred eight children completed the prospective follow-up until 3 years of age. INTERVENTIONS: None. MAIN RESULTS: The wheezing and pneumonia groups had equal viral and bacterial etiologic findings. History of wheezing, atopic eczema, and elevated serum IgE levels were more common in patients with wheezing than with pneumonia. Subsequent wheezing was seen after bronchiolitis in 76% (61 of 80) of the children at 1 to 2 years of age and in 58% (44 of 76) at 2 to 3 years of age. The respective figures were significantly lower, 9% (three of 33) and 16% (five of 32), in patients with pneumonia. An analysis of risk factors did not reveal any with a significant effect on subsequent wheezing. CONCLUSIONS: Subsequent wheezing is common after bronchiolitis, but rare after early childhood pneumonia, although caused by the same viruses or bacteria. Atopic diathesis is the host factor associated with initial wheezing. No genetic or environmental risk factor had significant association with later wheezing. PMID- 8506831 TI - Abdominal symptoms as presentation of hypertensive crisis. AB - OBJECTIVE: To describe a series of patients in hypertensive crisis who presented primarily with abdominal symptoms. DESIGN: Patient reports. SETTING: Referral center after initial presentation in the general community. PARTICIPANTS: Three children, aged 10 months to 4 years, in hypertensive crisis who presented with abdominal symptoms that promptly resolved and did not recur with blood pressure control. CONCLUSIONS: Blood pressure should be measured in all children undergoing physical examination; particular attention should be paid to the blood pressure of patients with unexplained abdominal symptoms before extensive diagnostic testing is pursued. PMID- 8506830 TI - The pattern of growth failure in Rett syndrome. AB - OBJECTIVE: To define the growth pattern of girls with Rett syndrome with respect to height, weight, and fronto-occipital head circumference. DESIGN: Longitudinal with irregular intervals between measurements. SETTING: Rett Syndrome Program Project at Baylor College of Medicine, Houston, Tex. PARTICIPANTS: Ninety-six girls fulfilling criteria for Rett syndrome; comparison group with standard growth curves. SELECTION PROCEDURE: Consecutive entries into the Rett Syndrome Program Project. INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: Height, weight, and fronto-occipital head circumference data were grouped into intervals. Group medians were then generated. Regression lines were fitted through the median points and plotted on standard growth charts. Deceleration of growth velocities began at age 3 months and persisted through age 18 years. CONCLUSIONS: Early deceleration of head growth, followed by deceleration of weight and height measurements, appears to be a growth pattern characteristic of Rett syndrome. This pattern of growth may provide the earliest clinical indicator for the diagnosis of Rett syndrome. PMID- 8506832 TI - A sleep position-dependent mechanism for infant death on sheepskins. AB - OBJECTIVE: To determine whether rebreathing of expired air is a plausible lethal mechanism of sudden death in infants sleeping face down on sheepskins. DESIGN: Case reports of infants who died on sheepskins combined with a controlled study of effects of their respiratory microenvironment at death. SETTING: Research laboratory. MATERIALS: Rabbits used experimentally to assist in simulation of an infant's respiratory microenvironment. Rabbits breathed into sheepskin through the airway of an infant mannequin. INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: Rebreathing of expired air was documented by carbon dioxide analysis of airway gas. Arterial blood gas analysis showed hypoxemia, hypercarbia, and acidosis in all experimental rabbits but not in controls. Rebreathing expired air was lethal for three of four experimental rabbits. CONCLUSIONS: Infants sleeping prone on a sheepskin, with their faces straight down, experience potentially lethal rebreathing of expired air. Avoidance of the prone position would markedly reduce the risk of rebreathing expired air. The pronounced decrease in sudden infant death syndrome in southern New Zealand that followed a campaign to eliminate prone sleeping may have been attributable to reduced fatal rebreathing, as deaths of infants sleeping face down on sheepskins were common before the campaign. PMID- 8506833 TI - Pituitary stalk and ectopic hyperintense T1 signal on magnetic resonance imaging. Implications for anterior pituitary dysfunction. AB - OBJECTIVE: To determine if improved delineation of hypothalamic-pituitary neuroanatomy by magnetic resonance imaging, especially the posterior pituitary hyperintense T1 signal, can be correlated with anterior and posterior pituitary endocrine function. DESIGN: Children with ectopic posterior pituitary tissue were identified at the Endocrine Clinic of the Children's Hospital of Pittsburgh (Pa) and their records were reviewed. PARTICIPANTS: Ten children with ectopic posterior pituitary tissue. MEASUREMENTS: Anterior pituitary hormone status, determined by standard testing, was correlated with the morphologic anomalies of the hypothalamic-pituitary region on magnetic resonance imaging. RESULTS: Patients were categorized by the appearance of the pituitary stalk based on the magnetic resonance image: attenuation of the stalk (group 1) or nonvisualization of the stalk (group 2). Patients in group 1 retained partial anterior pituitary function. Patients in group 2 had panhypopituitarism. CONCLUSION: Prospective evaluation of affected individuals may provide insight into the pathophysiologic mechanisms of idiopathic hypopituitarism. PMID- 8506834 TI - Long-term effectiveness of depot gonadotropin-releasing hormone analogue in the treatment of children with central precocious puberty. AB - OBJECTIVE: To assess the efficacy and safety of a long-acting gonadotropin releasing hormone analogue (GnRHa), leuprolide acetate for depot suspension (Lupron Depot), in the treatment of central precocious puberty in children, and to determine the reversibility of GnRHa therapy after it has been discontinued. RESEARCH DESIGN: Children with documented central precocious puberty were treated with Lupron Depot for 1.6 to 3.5 years. Their course of pubertal development, growth rate, skeletal maturation, and response to gonadorelin hydrochloride testing were compared before and during treatment. For those girls who finished treatment, an assessment of the reversibility of the GnRHa was performed by documenting a return to pubertal responses to gonadorelin testing, and by documenting menarche at an appropriately mature bone age. SETTING: Community teaching hospital. PATIENTS: Ten girls with central precocious puberty defined as pubertal maturation statistically advanced for age combined with a pubertal gonadotropin response to gonadorelin testing. Children who had been treated for less than 1.5 years were excluded, as were those with congenital adrenal hyperplasia. Patients who finished treatment have been followed up for up to 5 years, and will continue in follow-up throughout their reproductive life. SELECTION SAMPLE: A consecutive group of children with documented central precocious puberty was studied. INTERVENTIONS: Lupron Depot was administered as a single monthly subcutaneous injection to each patient. Treatment was usually discontinued by 10 to 11 years of age, at which time pubertal progression was allowed to resume. MEASUREMENT AND RESULTS: Mean peak serum concentrations of follicle-stimulating and luteinizing hormone responses to gonadorelin testing decreased significantly after the initial dose (from 21.8 +/- 4.5 [+/- SEM] to 2.4 +/- 0.2 IU/L for follicle-stimulating hormone and from 50.1 +/- 11.2 to 5.0 +/- 0.8 IU/L for luteinizing hormone) and remained suppressed for the duration of treatment. The progression of puberty slowed or reversed in all patients. Mean growth rate for chronologic age was significantly increased initially by 3.9 SDs and decreased to 0.9 SDs during treatment. The mean rates of skeletal maturation divided by the change in chronologic and height age changes over time were advanced (1.4 +/- 0.1 and 1.1 +/- 0.15, respectively) at the onset of therapy and decreased significantly to 0.7 +/- 0.1 and 0.8 +/- 0.1, respectively, on treatment. There was an increase in mean predicted height of 3.4 cm for all patients, and this was statistically significant. Thus, treatment with Lupron Depot at least maintained the predicted height at the onset of therapy. Girls who completed their course of treatment had pubertal gonadotropin responses to gonadorelin testing within 2 to 6 months, and menarche within the first year if skeletal maturation reached 13.0 to 13.5 years. No significant side effects of therapy were noted. CONCLUSIONS: Treatment of central precocious puberty in children using Lupron Depot is safe and efficacious. Its effects are readily reversible after treatment is discontinued, and menarche occurs at a normal bone age. Measurement of serum luteinizing hormone concentrations using an assay that is specific for the beta-subunit is necessary to monitor chemical suppression of luteinizing hormone during treatment. Longer-term studies, including reproductive history, will be needed before the potential effects of treatment on fertility can be assessed. PMID- 8506835 TI - Follow-up of preterm infants treated with dexamethasone for chronic lung disease. AB - OBJECTIVE: To study the outcome of prolonged treatment with dexamethasone sodium phosphate in preterm infants who depend on assisted ventilation. DESIGN: Longitudinal follow-up using historic controls. SETTING: Regional intensive care nursery. PARTICIPANTS: Sixty-one very-low-birth-weight infants treated with a 42 day course of dexamethasone and 61 historic controls matched for birth weight, gestational age, race, and sex. All 122 subjects required assisted ventilation for at least 15 days. INTERVENTION: Infants were given dexamethasone sodium phosphate at a dose of 0.5 mg/kg per day. The dose was then tapered over 42 days. MEASUREMENTS/MAIN RESULTS: Infants treated with dexamethasone received assisted ventilation for a median of 33 days; controls, a median of 47 days (P < .05). One hundred infants survived; 94 were examined at age 1 year. The two groups were similar with respect to the proportions hospitalized for respiratory infection in the first year of life and the proportions with weight, length, and head circumference below the fifth percentile. Rates of cerebral palsy were also similar between the two groups, as were median Bayley Mental and Psychomotor developmental index scores. CONCLUSIONS: Dexamethasone treatment was associated with fewer days of assisted ventilation, but not with improved outcome at age 1 year. More assessment should be made of dexamethasone's effect on long-term outcome before dexamethasone becomes widely used in preterm infants who depend on assisted ventilation. PMID- 8506836 TI - Prolonged pH monitoring is of limited usefulness for gastroesophageal reflux. AB - OBJECTIVE: To assess the diagnostic value of pH monitoring. DESIGN: A prospective study. SETTING: Pediatric university hospital serving as a secondary and tertiary referral center. PARTICIPANTS: Thirty-eight infants, aged 1 to 12 months, and 26 children, aged 13 months to 18 years, admitted during a 2-year period because of clinically significant gastroesophageal reflux (GER). INTERVENTIONS: Prolonged (20-hour) pH monitoring as well as endoscopy and biopsy of the esophagus were carried out in all patients who, on the basis of clinical data, were classified as having mild, moderate, or severe GER disease. RESULTS: In the infant group, results of prolonged pH monitoring were abnormal in 34 (89.5%). In the older group, results were abnormal in less than half (11 [42.3%]) of the cases. In both groups, pH monitoring data did not correlate with the severity of GER disease or of esophagitis. Severity of GER disease was not predictive of esophagitis. CONCLUSIONS: (1) Endoscopy and biopsy of the esophagus should be the first procedures whenever there are clinical findings of moderate to severe GER disease. (2) Monitoring of pH should be restricted to those patients without a clear-cut history of GER disease. PMID- 8506837 TI - Surfactant therapy failure identifies infants at risk for pulmonary mortality. AB - OBJECTIVE: To characterize the clinical features of infants who do not respond to surfactant therapy. DESIGN: Patient series, chart review. SETTING: Academic referral neonatal intensive care unit. PATIENTS/SELECTION: Ninety-nine consecutive infants with respiratory distress syndrome who received surfactant therapy and 107 infants from the 2 years prior to initiation of surfactant therapy matched for birth weight, race, sex, gestational age, chronological age, and disease severity. MEASUREMENTS/RESULTS: Oxygen index was used to quantitate response to surfactant therapy. A 25% decrease in oxygen index 6 hours after the first surfactant dose was significantly different from that of the matched historical cohort (P = .04). Oxygen index decreased 25% or more in 49 infants, the response group, while oxygen index decreased less than 25% or increased following therapy in the remaining 50 infants, the nonresponse group. Pulmonary interstitial emphysema occurred more frequently in the nonresponse group. The only deaths from pulmonary causes at 10 days of age or younger occurred in the nonresponse group (n = 11). CONCLUSIONS: Pulmonary processes unresponsive to surfactant therapy contribute to morbidity and mortality in newborn respiratory distress syndrome. Classifying respiratory distress syndrome as "surfactant responsive" or "surfactant unresponsive" offers a scheme by which to investigate alternative explanations and interventions for newborn respiratory distress syndrome. PMID- 8506838 TI - Rhabdomyoma and ventricular preexcitation syndrome. A report of two cases and review of literature. AB - OBJECTIVE: A description of two infants with ventricular preexcitation syndrome and supraventricular tachycardia associated with rhabdomyoma and review of the literature. DESIGN: A review of two patients who were seen between 1981 and 1986 in the cardiology department. SETTING: Pediatric Heart Institute at St Christopher's Hospital for Children, Philadelphia, Pa. PARTICIPANTS: Two newborn female infants with ventricular preexcitation syndrome, supraventricular tachycardia, rhabdomyomatous tumor of the heart, and tuberous sclerosis are described. RESULTS: The first patient had unsuccessful partial resection of the rhabdomyomatous tumors obstructing the tricuspid valve and right ventricular cavity and died immediately after surgery. By histologic examination, no direct accessory connection was noted between the myocardial fibers of atria and ventricles through annulus fibrosus. By gross examination, the tumor extended from the right atrium through the tricuspid valve to the right ventricular cavity, suggestive of macroscopic accessory connection. The second patient presented with unsustained ventricular tachycardia and obstructive subaortic rhabdomyoma, requiring emergency surgery. One week later, reentrant supraventricular tachycardia developed and she required digoxin therapy for 15 months. CONCLUSIONS: Infants with rhabdomyomatous tumor of the heart and ventricular preexcitation syndrome may have microscopic or macroscopic accessory connections. Cardiac tumors like rhabdomyoma and oncocytic tumors should be suspected in infants with ventricular preexcitation syndrome or supraventricular tachycardia. PMID- 8506839 TI - Resolved: the proliferation of subspecialties is not in the best interests of general pediatrics. Ambulatory Pediatric Association debate. PMID- 8506840 TI - Pediatric environmental health training. Impact on pediatric residents. AB - OBJECTIVE: To determine whether incorporation of a course in pediatric environmental health into a pediatric residency program would alter residents' behavior in history taking. DESIGN: Retrospective chart review. SETTING: Large pediatric training hospital in northern California. PARTICIPANTS: Twenty-three children admitted with asthma by 12 pediatric residents in June 1991 and a control group of 28 children admitted with asthma by 17 pediatric residents in June 1990. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The initial history and physical assessments were examined for all patients with status asthmaticus admitted to Children's Hospital Oakland (Calif) in June 1990 and 1991. Chi-square analysis revealed a significant difference in the number of environmental questions asked in the group trained in pediatric environmental health compared with the group that received no instruction. CONCLUSIONS: The incorporation of a course in pediatric environmental health markedly affected pediatric residents' behavior in assessing environmental causes for common illnesses. We recommend that the course, "Kids and the Environment," be incorporated into other pediatric residency programs, and that the efficacy of the course be determined by chart review. PMID- 8506841 TI - Radiological cases of the month. Pulmonary sling anomaly of the left pulmonary artery. PMID- 8506842 TI - Radiological cases of the month. Menetrier's disease. PMID- 8506843 TI - Picture of the month. Aplasia cutis congenita. PMID- 8506844 TI - Pathological cases of the month. Infantile fibrosarcoma. PMID- 8506845 TI - Pathological cases of the month. Lymphomatoid granulomatosis. PMID- 8506846 TI - Threshold limit values, permissible exposure limits, and feasibility: the bases for exposure limits in the United States. AB - The development of exposure limits in the United States has always relied heavily upon the threshold limit values (TLVs) developed by the American Conference of Governmental Industrial Hygienists (ACGIH). In fact, the TLVs were adopted as official exposure limits by the Occupational Safety and Health Administration (OSHA) in 1972 and 1989. Given the continuing importance of the ACGIH limits, this paper compares the basis of the TLVs with that employed by OSHA de novo in its 12 new permissible exposure limits (PELs). Using benzene as an example, it is shown that OSHA's new PELs have been established following a rigorous assessment of the inherent risks and the feasibility of instituting the limit. The TLVs, on the other hand, have been developed by ad hoc procedures and appear to have traditionally reflected levels thought to be achievable at the time. However, this might be changing. Analysis of the historical reductions of TLVs, for 27 substances on the 1991-1992 list of intended changes, indicates smaller reductions in the past (median reduction of 2.0-2.5-fold between 1946 and 1988) compared to those currently being observed (median reduction of 7.5-fold between 1989 and 1991). Further analysis suggests a more aggressive policy of the ACGIH regarding TLVs for carcinogens but not for substances that produce effects other than cancer. Regardless of whether the basis of the TLVs has changed recently, it would take a relatively long time for the impact of any change to be felt, since the median age of the 1991-1992 TLVs is 16.5 years, and 75% of these limits are more than 10 years old. The implications of OSHA's continued reliance on the TLVs as a means of updating its PELs are discussed, and four alternatives are presented to the ACGIH regarding the future of its activities related to exposure limits. It is concluded that new mechanisms are needed for OSHA to update its PELs in a timely fashion so that the TLVs will not be adopted by default in the future. PMID- 8506847 TI - Worker awareness of exposure: industries and occupations with low awareness. AB - A goal of occupational health is to inform workers of hazards on their jobs. This analysis addresses this goal by identifying industries and occupations with low worker awareness of potential exposures. Industries and occupations were ranked by the greatest positive difference between the proportion of workers exposed and proportion perceiving exposure to chemical and physical hazards. Those with low awareness had the greatest difference, i.e., high exposure and low perception. This analysis was performed by adding exposure data from a national exposure survey to a national health survey with perceived exposure data. The hospital and construction industries and occupations in these industries ranked among the top five for all hazards. For example, for hospital workers the difference between proportion exposed and proportion perceiving exposure to chemicals was 62% and to radiation was 42%, and for workers in construction the difference was 54% for exposure to noise and 63% for exposure to vibration. PMID- 8506848 TI - Body fluid exposure in an urban tertiary care medical center. AB - The increasing prevalences of the human immunodeficiency (HIV) and hepatitis B viruses have focused attention on the risks that health care workers face when exposed to potentially infective body fluids. This study establishes a profile of 320 parenteral exposure incidents and 47 exposure incidents to mucous membranes or abraded skin, reported in our medical center between July 1988 and July 1990. We found that 102 (27.8%) of the incidents involved an HIV-positive patient, that 130 (35.4%) of the reporting employees had completed their hepatitis B vaccination at the time of the incident, and that, although the majority of incidents involved employees with patient contact, unfortunately, service workers also were represented (4.6%, n = 17). Factors contributing to incidents included recapping (10.9%, n = 40), full needle-boxes (7.6%, n = 28), and inappropriate disposal (13.1%, n = 48). A health fair featuring walk-in hepatitis B immunization attracted 260 participants, 90% of whom completed the entire immunization series. This significantly improved the immunization rate of employees subsequently reporting body fluid exposure. PMID- 8506849 TI - Penetration of industrial chemicals across the skin: a predictive model. AB - The recently reported dermal absorption and toxicity potential of industrial chemicals is reconsidered using an alternative physicochemically based model of skin penetration. In this model, the outermost, and least permeable, component of the skin [namely, the stratum corneum (SC)] is considered to provide only a lipoidal transport pathway into the body for chemicals that come into contact with the skin. The predictive algorithm of the model is biophysically compatible with known SC properties, and is based on experimental determinations of permeability coefficients through human skin in vitro for nearly 100 compounds of widely divergent physicochemical properties. This simpler prediction results in significantly lower estimates of maximum percutaneous penetration fluxes. PMID- 8506850 TI - Evaluation of skin symptoms among workers at a Swedish paper mill. AB - Process and office workers at a Swedish paper mill (n = 274) and dairy workers (n = 45) were investigated with questionnaires regarding skin symptoms. In the second part of the study, subjects reporting skin symptoms and a random sample of subjects without symptoms were examined and investigated with patch testing. Pruritus and skin irritation probably related to exposure to dust were found. The results do not indicate an increased prevalence of contact allergy. In two cases, positive patch test reactions to paper size (rosin) and a slimicide, mercaptobenzothiazole (MBT), were noted. PMID- 8506851 TI - Cancer and other causes of death among male and female farmers from twenty-three states. AB - Occupation and industry codes on death certificates from 23 states for 1984-1988 were used to evaluate mortality risks among white and nonwhite, male and female farmers. Proportionate mortality and proportionate cancer mortality ratios were calculated using deaths among nonfarmers from the same states to generate expected numbers. Among farmers there were 119,648 deaths among white men, 2,400 among white women, 11,446 among nonwhite men, and 2,066 among nonwhite women. Deficits occurred in all race-sex groups for infective and parasitic diseases, all cancer combined, lung cancer, liver cancer, diseases of the nervous system, multiple sclerosis, hypertension, and emphysema. As reported in other studies, white male farmers had excesses of cancer of the lymphatic and hematopoietic system, lip, eye, brain, and prostate. Excesses of cancers of the pancreas, kidney, bone, and thyroid were new findings. Regional patterns were evident, particularly among white men. Significant excesses for accidents, vascular lesions of the central nervous system (CNS), and cancers of the prostate tended to occur in most geographic regions, while excesses for mechanical suffocation, non-Hodgkin's lymphoma, and cancers of the lip, brain, and the lymphatic and hematopoietic system were limited to the Central states. Increases among nonwhite men were similar to those in white men for some causes of death (vascular lesions of the CNS and cancers of the pancreas and prostate), but were absent for others (lymphatic and hematopoietic system, lip, eye, kidney, and brain). Women (white and nonwhite) had excesses for vascular lesions of the CNS, disease of the genitourinary system (white women only), and cancers of the stomach and cervix (nonwhite women only). Cancer of the buccal cavity and pharynx was slightly elevated among women, and white women had nonsignificant excesses of multiple myeloma and leukemia. Excesses for leukemia and non-Hodgkin's lymphoma occurred among white men and women, but not among nonwhites. Excesses for several types of accidental deaths were seen among all race-sex groups. PMID- 8506852 TI - Respiratory health status in swine producers using respiratory protective devices. AB - A cross-sectional survey on respiratory health in swine producers showed that 30% of 301 examined men usually used a dust mask when working inside a barn. They did not differ significantly from dust mask nonusers in respect to respiratory symptoms and lung function. This analysis was undertaken to determine whether the respiratory health of dust mask users was associated with reasons why they had started individual respiratory protection. The subjects were recontacted in order to identify those who started using a mask to deliberately prevent symptoms (42 men) and those who started protection because of pre-existing respiratory symptoms (44 men). Not unexpectedly, between-group comparisons of respiratory symptoms and lung function suggest that swine producers who wear dust masks for preventive purposes have better respiratory health than those who wear dust masks because of symptoms or those who do not use individual respiratory protection. The individual reasons for starting dust mask usage should be examined among potential determinants of the outcomes of prospective studies which can then provide more valid assessment of the effect of individual respiratory protection. PMID- 8506853 TI - Respiratory function in sewage workers. AB - Respiratory symptoms and ventilatory capacity were studied in a group of 74 sewage workers employed in cleaning the city sewage system of Zagreb, Croatia. Workers were studied by their work stations: closed channels (N = 26), drainage (N = 31), and other sewage workers (N = 17). The prevalence of chronic respiratory symptoms was higher in closed channel and drainage workers than in controls, particularly for chronic cough (range: 41.9-46.2% vs. 14.3%), chronic phlegm (range: 38.7-46.2% vs. 14.3%), chronic bronchitis (range: 32.3-42.3% vs. 8.6%), and chest tightness (range: 29.0-53.8% vs. 0%). In the first two groups of sewage workers there was a high prevalence of acute symptoms which developed during the work shift, being particularly pronounced for eye irritation (range: 16.1-26.9%), dyspnea (16.1-23.1%), dizziness (range: 6.5-23.1%), throat burning (9.7-19.2%), and skin irritation (range: 22.6-26.9%). Baseline ventilatory capacity was significantly decreased compared to predicted values in sewage workers; in particular, values for FEF50 and FEF25 were reduced, suggesting obstructive changes in smaller airways. Our data indicate that sewage workers experience frequent acute and chronic respiratory symptoms and exhibit objective evidence of respiratory dysfunction. PMID- 8506854 TI - Lead exposure among automobile radiator repair workers and their children in New York City. AB - Despite a comprehensive Occupational Safety and Health Administration lead standard, exposure to lead continues in many industries. This paper describes a blood lead screening and education program for automobile radiator repair workers and their families in New York City. Results showed that 67% of automobile radiator repair workers (n = 62) in 89% of the shops tested (n = 24) had blood lead levels in excess of 25 micrograms/dl. The vast majority of workers had never been tested previously, and none had received health and safety training regarding occupational lead exposure. Although none of the workers' children's blood lead levels were in excess of then-current guidelines, several had levels which may be associated with subclinical toxicity and in excess of the revised Centers for Disease Control guidelines of 10 micrograms/dl. This project demonstrates that lead exposure in the automotive radiator repair industry continues to be widespread and that local health departments can assist in hazard identification and remediation. PMID- 8506855 TI - Solvent-induced chronic toxic encephalopathy. AB - Chlorinated solvents, especially trichloroethylene, have been extensively used for metal degreasing since the beginning of this century. There have been case reports of cranial nerve damage and symptoms of acute and reversible encephalopathy. However, another issue during the last decade is the possible existence of a syndrome of chronic cerebral dysfunction. Our study deals with the risk of developing a state of psychoorganic syndrome after long-term exposure to solvents, mainly trichloroethylene. In this historical cohort study, 96 metal degreasers participated in a clinical medical and psychological examination. The risk of developing psychoorganic syndrome was proportional to the exposure duration, to increasing age, and to decreasing primary intellectual level. Using logistic regression analysis, there was a significantly increased risk of developing psychoorganic syndrome from solvent exposure. There was an odds ratio of 5.6 (0.93-34.3) for psychoorganic syndrome in the medium-exposed group. In the most highly exposed group, with a mean full-time exposure duration of 11 years, there was a significantly increased risk of psychoorganic syndrome, the adjusted odds ratio was 11.2 (1.9-66.6). None of four other potential confounders (arteriosclerotic disease, neurologic/psychiatric disease, alcohol abuse, and current solvent exposure) had any significant associations to psychoorganic syndrome. PMID- 8506856 TI - Controlled short-time terpene exposure induces an increase of the macrophages and the mast cells in bronchoalveolar lavage fluid. AB - Eight healthy nonsmoking volunteers underwent terpene exposure (450 mg/m3 air) on 4 different occasions within a 2 week period. Total exposure time was 12 hours. Before and after the sequences of exposure, bronchoalveolar lavage was performed. Twenty hours after the exposure there was a significant (p < 0.05) increase of the alveolar cell concentration (median pre-exposure value 76 x 10(6) cells/L, post-exposure value 126 x 10(6) cells/L), predominantly due to an increment of the macrophages (from 72 x 10(6) cells/L to 121 x 10(6) cells/L). The mast cells also increased from 1/10 to 5/10 visual fields. No elevated concentrations of albumin, fibronectin, hyaluronan (hyaluronic acid), and tryptase were observed. We conclude that terpene exposure, in a concentration regarded as moderate, induces an acute alveolar cellular reaction in healthy subjects. PMID- 8506857 TI - Mortality of workers hired during World War II. AB - There has been some suggestion that men first hired during World War II do not show the typical healthy worker effect and may have been more unhealthy than their counterparts who entered military service. We have studied 41,000 workers at six plants to determine whether men hired during World War II had higher mortality than men hired just before or after WWII. No evidence was found of any "unhealthy WWII worker" effect. PMID- 8506858 TI - Unusual sex ratio of births to carbon setter fathers. AB - In the years of 1980-1990, there were 139 birth records filed in Washington State on which father's occupation was designated as "carbon setter," a job title specific to aluminum reduction plants of the prebake type. Fifty-three (53) of these records specified sex of the birth as male, while 86 records specified sex of the infant as female. This gives a sex ratio of 0.381, which is a significant departure from the usual sex ratio at birth (proportion male = 0.512). Surveillance of sex ratio by paternal occupation is a simple method of monitoring for genotoxicity. PMID- 8506859 TI - Pharmaceutical prices and health care reform. PMID- 8506860 TI - Development of ASHP practice standards. PMID- 8506861 TI - Arranging for time to develop clinical skills. PMID- 8506862 TI - Inline filtration of ondansetron hydrochloride during simulated i.v. administration. PMID- 8506863 TI - Staff pharmacist program for adjusting dosages on basis of creatinine clearance. PMID- 8506864 TI - OBRA's counseling requirement and pharmaceutical care. PMID- 8506865 TI - Comment on ASHP therapeutic guidelines. PMID- 8506866 TI - Improve pharmacist behavior and cut the gimmicks. PMID- 8506867 TI - Comments on ketorolac tromethamine for injection. PMID- 8506868 TI - Comments on ASHP guidelines for preventing medication errors. PMID- 8506869 TI - Comments on ASHP guidelines for preventing medication errors. PMID- 8506870 TI - Comments on ASHP guidelines for preventing medication errors. PMID- 8506871 TI - Defining excellence. AB - Excellence in the pharmacy profession, particularly pharmacy management, is defined. Several factors have a significant effect on the ability to reach a given level of excellence. The first is the economic and political climate in which pharmacists practice. Stricter controls, reduced resources, and the velocity of change all necessitate nurturing of values and a work ethic to maintain excellence. Excellence must be measured by the services provided with regard to the resources available; thus, the ability to achieve excellence is a true test of leadership and innovation. Excellence is also time dependent, and today's innovation becomes tomorrow's standard. Programs that raise the level of patient care, not those that aggrandize the profession, are the most important. In addition, basic services must be practiced at a level of excellence. Quality assessment is a way to improve care and bring medical treatment to a higher plane of excellence. For such assessment to be effective and not punitive, the philosophy of the program must be known, and the goal must be clear. Excellence in practice is dependent on factors such as political and social norms, standards of practice, available resources; perceptions, time, the motivation to progress to a higher level, and the continuous innovation required to reshape the profession to meet the needs of society. PMID- 8506872 TI - Pharmacy technicians and computer technology to support clinical pharmacy services. AB - Use of pharmacy technicians, computer-assisted patient-selection algorithms, and bar-code technology to increase efficiency of clinical pharmacy staff is described. Workload assessment showed that clinical pharmacists at Henry Ford Hospital (Detroit) were spending two thirds of their time with data collection, patient selection, and documentation and only one third of their time intervening to improve drug therapy. To increase pharmacist efficiency, two technicians were hired to perform the clerical functions associated with clinical pharmacy services. Also, a bar-code data-collection system was implemented to help pharmacists document their clinical activity. Computerized algorithms helped pharmacists target patients whose therapy should be most carefully reviewed. Reports generated by the system summarized workload distribution and provided information about the types of problems identified and corrected. After these changes were implemented, the fraction of time that pharmacists spent intervening to improve drug therapy increased to one half. Use of technicians to perform clerical tasks, computerized algorithms to help identify patients in need of pharmacist assistance, and bar-code technology to facilitate data collection has helped clinical pharmacists improve their time management. PMID- 8506873 TI - Drug-use evaluation programs in short-term-care general hospitals. AB - The results of a survey to assess drug-use evaluation (DUE) programs in short term-care general U.S. hospitals are reported. During February 1992, questionnaires were mailed to pharmacy directors at 491 randomly selected short term-care general hospitals with 100 or more beds. The questionnaire was designed to collect information on the characteristics of surveyed hospitals and their pharmacies, DUE program characteristics, and the perceptions of pharmacists about the DUE programs. The net response rate was 66.6% (327 usable replies). Pharmacists involvement in DUE program activities was found to be very high, with two thirds of respondents indicating they participated in all five ASHP recommended activities. Pharmacists rated the effectiveness of current DUE programs as moderate, while the importance of pharmacist participation was perceived to be very high. Pharmacists were members of 97.9% of the respondents' DUE committees, but only 65.5% of the pharmacist members held voting privileges. Pharmacists reported devoting an average of 11.27 hours weekly to DUE-related tasks. Reasons used to select drugs for DUEs, interventions employed, uses of DUE results, and methods of evaluating the effectiveness of DUE programs all varied widely. In short-term-care general hospitals with 100 or more beds, pharmacists assigned to DUE activities were highly involved in DUE committees and programs. The effectiveness of these activities needs to be assessed in more detail. PMID- 8506874 TI - Regional pharmacokinetics educational program. AB - An educational program for hospital pharmacists in and near Vermont is described and its impact on departmental clinical practice evaluated. Pharmacists were instructed by practitioners from a single institution in basic pharmacokinetics, practice guidelines for aminoglycoside therapy, and use of a computer program for aminoglycoside dosage determination. Participants completed a multiple-choice precourse test, a similar postcourse test, and a third test six months after class completion. Test scores were compared with those from a control group of pharmacists. Pharmacy directors from study group hospitals completed questionnaires measuring aminoglycoside clinical services before and six months after the program. Compared with the control group, participants scored higher on the postcourse tests. Results from the questionnaire indicate that the program affected clinical practice in almost all participating pharmacy departments. A consistent pharmacokinetic strategy for reviewing aminoglycoside dosages and evaluating serum aminoglycoside concentrations is now practiced in most Vermont hospitals. An educational program originating in one hospital can expand pharmacists' knowledge and influence departmental clinical practice throughout a region. PMID- 8506875 TI - Stability of metoprolol tartrate in 5% dextrose injection or 0.9% sodium chloride injection. AB - The stability of metoprolol tartrate 0.40 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored at 24.0 +/- 2.4 degrees C was studied. Triplicate admixtures of each solution were prepared. A stability-indicating high-performance liquid chromatographic assay was used to determine metoprolol tartrate concentrations. At 0, 6, 12, 24, and 36 hours, samples were visually assessed then assayed in duplicate. Stability was defined as a < 10% decline in metoprolol tartrate concentration from the time 0 determination. No notable color changes or precipitation was observed in any sample. All samples demonstrated a < 7% reduction in metoprolol tartrate concentration over 36 hours. Metoprolol tartrate 0.40 mg/mL admixed in 5% dextrose injection or 0.9% sodium chloride injection in PVC bags and stored at 24.0 +/- 2.4 degrees C was stable for 36 hours. PMID- 8506876 TI - Confidentiality of a patient's disclosure of symptoms. PMID- 8506877 TI - Preparing to implement an information system. AB - The factors that must be considered when preparing to implement a pharmacy information system are discussed. A major early decision is whether to locate the central processing unit (CPU) in the pharmacy department or the information services department. Other site considerations are the size of the CPU, environmental conditions, electrical needs, the presence of a backup CPU, and system security. System considerations include interfaces, daily management, preventive maintenance, other support functions, and printers. The system will affect all personnel in the pharmacy department; most jobs will have to be redesigned. Issues to address during implementation planning are forms and labels, the implementation schedule, benchmark development, system conversion, and problem resolution. Files must be developed with great attention to detail and accuracy, as they are the heart and soul of the system. Most departmental policies and procedures will have to be incorporated into the operations of the system. Other departments--in particular, information services, hospital purchasing, administration, nursing, and laboratory--may have requirements that should be considered. There may be legal requirements in the areas of drug order entry, file security and confidentiality, and retention of records. Extensive preparation and planning are necessary before a pharmacy information system can be implemented. PMID- 8506878 TI - The argument for therapeutic use of heroin in pain management. PMID- 8506879 TI - The argument against therapeutic use of heroin in pain management. PMID- 8506880 TI - The bottom line in asthma management is patient education. PMID- 8506881 TI - A controlled trial of two forms of self-management education for adults with asthma. AB - PURPOSE: Excess morbidity and mortality due to asthma, aggravated by demonstrably poor patient self-management practices, suggest the need for formal patient education programs. Individual and group asthma education programs were developed and evaluated to determine their cognitive, behavioral, and clinical effects. PATIENTS AND METHODS: We compared changes in asthma symptoms, utilization of medical services, knowledge about asthma, metered-dose inhaler (MDI) technique, and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were randomly assigned to small-group education, individual teaching, or 1 of 2 control conditions--an information (workbook) control or usual control (no formal asthma education). Data were collected from patients by questionnaire, diary, and physical examination at enrollment and at 5 months and 1 year after intervention. Medical record data on these patients were abstracted for a total 3-year period, from 1 year before to 2 years after enrollment. RESULTS: Compared with the usual control, the self-management education programs were associated with significant improvements in control of asthma symptoms (reduced "bother" due to asthma and increased symptom-free days), MDI technique, and environmental control practices. Small-group education also was associated with significant improvements in physician evaluation of the patients' asthma status and in patients' level of physical activity. For both group and individual education recipients, improvement in MDI technique was positively correlated with improved control of symptoms; however, the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone. The time course over which changes occurred in the various outcome measures suggests the mechanism by which education resulted in improvement in the patient's status. Significant improvements in MDI technique and environmental control practices were manifest immediately following education (5-month follow-up) and at the 1-year follow-up. Significant improvements in symptom measures were not apparent until the 1-year follow-up. The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period, but this decrease did not differ significantly among treatment conditions. However, there was a trend toward greater reduction in patients receiving small-group education. An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed. This result must be regarded as tentative, since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues. However, this trend is consistent with the antecedent benefits of the small-group education, and appears to warrant further investigation. CONCLUSIONS: Carefully designed asthma education programs for adults can improve patients' understanding of their condition and its treatment and increase their motivation and confidence that the condition can be controlled, thereby increasing their adherence to the treatment regimen and management of symptoms, and, in turn, improving control of symptoms. Both small-group education and individual education were associated with significant benefits, but the group program was simpler to administer, better received by patients and educators, and more cost-effective. The results show promise for improving clinical outcomes, through well-designed educational programs, for patients with asthma and other chronic health problems. PMID- 8506882 TI - Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture documented Lyme borreliosis associated with erythema migrans: report of a prospective study. AB - BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time. PMID- 8506883 TI - Screening elderly populations for cobalamin (vitamin B12) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry. AB - PURPOSE: This study assesses the value of the urinary methylmalonic acid (MMA) assay by gas chromatography mass spectrometry as a screening procedure for detection of cobalamin (Cbl) deficiency and estimates the prevalence of undetected Cbl deficiency in elderly populations. SUBJECTS AND METHODS: A total of 809 elderly individuals over age 65 were screened using random spot urine specimens from 4 different sites: a health fair, retirement apartments, a hospital-based elderly assessment center, and a nursing home. Follow-up tests included serum total Cbl, serum MMA, and normalization of urinary and serum MMA levels with Cbl intramuscular (IM) therapy. RESULTS: The prevalence of elevated urinary MMA varied across population groups, from 3.0% in elderly visiting a health fair to 5.1% in elderly residing in retirement apartments. Follow-up on 35 of 36 subjects with elevated urinary MMA levels showed that 18 had low serum total Cbl (less than 180 pg/mL at Hospital 1 or less than 200 pg/mL at Hospital 2), 12 had low-normal Cbl (180 or 200 pg/mL to 350 pg/mL), and 5 had normal Cbl. Of the 12 subjects with low-normal Cbl on retesting, further assessment was performed in 7, and all 7 of these subjects had evidence of Cbl deficiency. Cbl IM therapy was initiated for 23 subjects; 16 were seen for follow-up and all had normal urinary MMA. CONCLUSION: The relatively high prevalence of undetected Cbl deficiency identified in the seniors warrants additional studies of elderly populations. The sensitivity, convenience, and noninvasive nature of the urinary MMA assay by gas chromatography mass spectrometry make it a practical screening test. PMID- 8506884 TI - Association of osteoporotic vertebral compression fractures with impaired functional status. AB - PURPOSE: To determine if vertebral compression fractures in elderly women were associated with impairments in physical, functional, and psychosocial performance. SUBJECTS AND METHODS: Ten white women with confirmed vertebral compression fractures were age- and race-matched with 10 control subjects without fractures in a case-control design. All subjects invited to participate in this study were patients of the Geriatrics Division of the Department of Medicine at Duke University Medical Center. All study participants lived either in the community or in the independent-living sections of local retirement communities in and around Durham, NC. Subjects with fractures (mean age = 81.9 years, SD = 5.9 years) had two or more vertebral compression fractures in their medical records, whereas control subjects (mean age = 79.6 years, SD = 6.5 years) had no history of vertebral fractures. Spinal radiographs of all women confirmed group assignment. Physical, functional, and psychosocial performances were evaluated. Physical performance was assessed by measurements of maximal trunk extension torque and thoracic and lumbar spinal motion in the sagittal plane, functional reach, mobility skills, 10-ft timed walk, and 6-minute walk test. Thoracic and lumbar spinal configurations were also determined. Functional performance was assessed using the Functional Status Index. Psychosocial performance was assessed with the following scales: Hopkins Symptom Checklist 90 Revised, Rosenberg Self Esteem Scale, West Haven-Yale Pain Inventory, Beck Depression Inventory, and single-item health-belief questions. RESULTS: Control subjects were not significantly different from patients with fractures in age, weight, number of current illnesses, number of prescribed medications, number of pain medications, ratings of lumbar spine degenerative disc disease, or lumbar spine facet joint arthritis. Activity levels and exercise participation were similar in both groups. Control subjects had no vertebral fractures, whereas fracture subjects had 4.2 +/- 2.6 fractures (range: 2 to 10). Thoracic kyphosis was increased and lumbar lordosis was reduced in fracture subjects. Fracture subjects had reduced maximal trunk extension torque, thoracic and lumbar spine sagittal plane motion, functional reach, mobility skills, and 6-minute walk test. The Functional Status Index showed reduced levels of functional performance in fracture subjects compared with controls with increased levels of assistance, pain with activity, and difficulty in activities. Psychosocial performance was limited in fracture subjects with increased psychiatric symptoms, increased pain, and greater perception of problems caused by health. CONCLUSION: Vertebral compression fractures are associated with significant performance impairments in physical, functional, and psychosocial domains in older women. PMID- 8506885 TI - Is the use of boxed gloves in an intensive care unit safe? AB - PURPOSE: To identify the type, rate, burden, and pattern of contamination of boxed, clean but nonsterile gloves in our intensive care unit (ICU). MATERIALS AND METHODS: The fingertips of the first, middle, and last two pairs of gloves in 29 boxes in routine service in our ICU were cultured. The first of each of these three sets were removed aseptically, the second in a routine fashion. RESULTS: We found 16 of 29 (55%) first pairs removed aseptically to be contaminated with a mean bioburden of 1.8 colony-forming units (CFU). The percentage contamination and bioburden did not change significantly with position in the box. Use of routine compared with strict aseptic technique increased the rate of contamination by only 11% (95% confidence interval [CI] -0.05 to +0.27 percentage points) and bioburden by only a mean of 3.4 colonies per pair (CI -0.51 to +4.90 CFU). The length of the time the boxes were open and in use was unrelated to whether the final aseptically removed pair was sterile or contaminated. The predominant organisms were coagulase-negative staphylococci. CONCLUSIONS: One half the pairs of latex examination gloves in our ICU were sterile despite repeated barehanded access to the boxes. Those contaminated exhibited a small bioburden of low pathogenic potential. No pattern of contamination or unsafe duration of box use were observed. The use of boxed, clean, nonsterile gloves appears safe for routine use in an ICU. PMID- 8506886 TI - Influence of labetalol on cocaine-induced coronary vasoconstriction in humans. AB - PURPOSE: Although labetalol is sometimes given to patients with cocaine associated chest pain, its influence on cocaine-induced coronary vasoconstriction is unknown. PATIENTS AND METHODS: In 15 patients (7 men, 8 women, aged 40 to 79 years) undergoing catheterization for chest pain, heart rate, mean arterial pressure, and coronary arterial area (by computer-assisted quantitative angiography) were measured (1) at baseline, (2) 15 minutes after intranasal cocaine, 2 mg/kg, then (3) 5 minutes after intravenous saline (n = 6) or labetalol, 0.25 mg/kg (n = 9). RESULTS: Of 40 coronary arterial segments analyzed, cocaine induced a 13% +/- 10% (mean +/- standard deviation) decrease in coronary arterial area in 32. Subsequently, no variable changed after saline administration. Although labetalol reduced mean arterial pressure (117 +/- 14 mm Hg after cocaine, 110 +/- 11 mm Hg after labetalol; p < 0.05), it induced no change in the coronary arterial area (3.47 +/- 1.37 mm2 after cocaine, 3.37 +/- 1.32 mm2 after labetalol; p = NS). CONCLUSION: Labetalol reverses the cocaine induced rise in mean arterial pressure, but does not alleviate cocaine-induced coronary vasoconstriction. PMID- 8506887 TI - Gross hematuria in residents of long-term-care facilities. AB - PURPOSE: To describe the epidemiology and characteristics of gross hematuria in elderly residents of nursing homes and to identify the associations of gross hematuria with urinary infection and the potential contribution of urinary infection to morbidity. PATIENTS AND METHODS: This was a prospective, descriptive study of episodes of gross hematuria identified by the nursing staffs at two long term-care facilities over 2 years. Episodes were characterized with respect to patient variables, presence of bacteriuria, duration of hematuria, therapeutic interventions, and genitourinary investigations. Clinical and serologic criteria were used to identify invasive infection. RESULTS: The incidence of gross hematuria was 31/100,000 resident days. Bacteriuria was present in 58 (74%) of 78 episodes with evaluable cultures. Fifty-two (61%) episodes lasted more than 24 hours, 25 (29%) were temporally associated with fever, and antimicrobials were given for 53 (61%) episodes. Gross hematuria occurred more frequently in men than in women and was more frequently associated with fever in men. Twenty-four (28%) episodes occurred in subjects with indwelling catheters, 30 (34%) in subjects with known genitourinary abnormalities, 26 (30%) in subjects with no genitourinary investigations, and 4 (4.6%) in subjects with genitourinary investigations but no abnormalities identified. No adverse clinical outcomes were identified in patients in whom antimicrobial therapy was not initiated. The maximal estimated incidence of invasive urinary infection associated with hematuria was 5.8/100,000 resident days, and of bacterial hemorrhagic cystitis, 6.3/100,000 resident days. CONCLUSIONS: These data suggest that underlying genitourinary abnormalities are present in most elderly institutionalized subjects with gross hematuria when genitourinary investigations are performed. Although bacteriuria is usually present, urinary infection, by itself, is an infrequent cause of gross hematuria. Afebrile hematuria without irritative symptoms probably does not require antimicrobial therapy. A standard approach to this clinical problem in the institutionalized elderly should be developed to optimize patient management and appropriate use of antimicrobial therapy. PMID- 8506888 TI - Computerized medical records and preventive health care: success depends on many factors. AB - OBJECTIVE: To study the effect of a computerized medical record and other practice factors on the delivery of preventive health care. DESIGN: Prospective, controlled trial. SETTING: University general internal medicine teaching clinic. PARTICIPANTS: Forty-five internal medicine residents and their 4 supervising attending physicians. INTERVENTION: The study group used a computerized ambulatory medical record system that included health care maintenance reminders. The control group used a conventional paper record with a health care maintenance flow sheet. MEASUREMENTS AND MAIN RESULTS: The computer reminders significantly increased health care maintenance recommendations made to patients for proctosigmoidoscopy, tetanus vaccination, influenza vaccination, and pneumococcal vaccination, but not for fecal occult blood testing, mammography, Pap smears, or serum thyroxine screening in the elderly. First-year residents were nearly twice as successful as third-year residents in overall health care maintenance. Success scores varied markedly depending on which attending physician was supervising the residents. We found a strong interaction among group assignment, supervising attending, and level of training such that the reminders doubled success scores among first-year residents supervised by two of the attending physicians but had little effect on other subgroups. The time of year and the format of the reminder also had important effects for some of the maneuvers. CONCLUSIONS: Although computerized medical records markedly improved the performance of prevention maneuvers by committed physicians, many physicians using computer systems failed to make use of the resource. The reasons for this were complex. Future work in this area should carefully control for personal behaviors and focus upon administrative changes that more effectively implement these potentially powerful tools. PMID- 8506889 TI - Response to a cholesterol-lowering diet: efficacy is greater in hypercholesterolemic subjects even after adjustment for regression to the mean. AB - PURPOSE: To define how much regression to the mean confounds apparent responsiveness in subgroup analyses, and to test, using techniques that remove regression to the mean, whether hypercholesterolemic subjects are more likely to respond to diet. PATIENTS AND METHODS: Data collected on 812 men and women participating in the Minnesota Coronary Survey Dietary Trial who had at least 2 total cholesterol measurements on a high-saturated-fat diet and 1 cholesterol measurement on a low-saturated-fat diet were analyzed for the effects of initial serum cholesterol and regression toward the mean on measurement of diet responsiveness. RESULTS: If regression towards the mean is not taken into account, dietary responsiveness in patients with mean cholesterol levels of 280 mg/dL was -25%, whereas dietary responsiveness in subjects with mean serum cholesterol levels of 156 mg/dL was -5%. After regression toward the mean was taken into account, subjects with high initial serum cholesterol levels had an 18% reduction in serum cholesterol levels whereas subjects with lower levels had an 11% reduction. Even after regression toward the mean is accounted for, subjects with high serum cholesterol levels were significantly more diet responsive (p < 0.005). CONCLUSION: The efficacy of a cholesterol-lowering diet for individuals can be overestimated or underestimated if only single measurements are used to determine response. Subjects with hypercholesterolemia, even after adjustment for regression towards the mean, are more diet-responsive than subjects with lower cholesterol levels. Dietary therapy should remain the first step in the treatment of hypercholesterolemia, and should also be effective in reducing cholesterol levels in the population at large. PMID- 8506890 TI - Can garlic reduce levels of serum lipids? A controlled clinical study. AB - PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems. PMID- 8506891 TI - High-density lipoprotein subfractions. AB - High-density lipoprotein (HDL) consists of a heterogeneous group of particles defined either by size or by apolipoprotein content. Subfractions of HDL appear to have distinct but interrelated metabolic functions, including facilitation of cholesteryl ester transfer to low- and very-low-density lipoproteins, modulation of triglyceride-rich particle catabolism, and, possibly, removal of cholesterol from peripheral tissues. Like HDL cholesterol, HDL subfractions are widely affected by a variety of factors. Subfractions also are markers for epidemiologic risk for coronary artery disease. Because they provide information about the physiologic processes of cholesterol metabolism, HDL subfractions are emerging as an increasingly important tool in the study of the relationship between lipids and cardiovascular disease. PMID- 8506892 TI - Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. PMID- 8506893 TI - Left-handed favor. PMID- 8506894 TI - Are things different in the light of day? A time study of internal medicine house staff days. AB - PURPOSE: To determine how internal medicine house staff spend their days and compare activities during the day with those previously observed during night call. SETTING: University-affiliated Veterans Affairs Medical Center. DESIGN: Two internal medicine house staff teams (one PGY-1 [postgraduate year] and one PGY-2 or PGY-3) observed during 5 short call admitting days. MEASUREMENTS: Time in each activity recorded by trained observers, computed, summed, and compared with that of similar activities of house staff on night call. RESULTS: House staff admitted an average of two patients each day. They spent, on average, 25 minutes per patient performing new patient histories and physical examinations, 29 minutes charting new patient information, and were interrupted after an average of 12 minutes during the new patient evaluation compared with 20, 19, and 7 minutes at night (p > 0.05). The average house officer spent 44 minutes in nonphysician duties and 11 minutes answering pages during the day. On average, house staff spent 3 minutes each day talking in person with patients' families. CONCLUSIONS: A significant amount of time each day was spent performing nonphysician duties. Little time was spent evaluating each patient or in person with patients' families and similar amounts of time were spent in charting and in patient evaluation. House staff appeared to spend more time with new patients during the day than they did at night, although this finding was not statistically significant. As noted during night call, evaluations were frequently interrupted. Future studies should examine why house staff choose to distribute their time in the manner described in this and similar studies. PMID- 8506895 TI - The role of oral candidiasis in survival and hospitalization patterns: analysis of an inner city hospital human immunodeficiency virus/acquired immune deficiency syndrome registry. AB - To assess the effect of oral candidiasis (OC) associated with human immunodeficiency virus (HIV) at initial hospital admission on both survival and hospital use, a retrospective analysis was performed in 1,172 hospitalized patients identified by an HIV surveillance program at an inner city public hospital in East Harlem, New York. Survival times were compared using three different HIV staging schemes placing patients with OC into either a common stage with adenopathy patients (Scheme IHS-URV), a common stage with acquired immune deficiency syndrome patients (AIDS; Scheme WRCDC), or an intermediate stage between AIDS patients and all others (Scheme ORAL). Patients without AIDS demonstrated a significantly increased risk of dying (relative risk, 2.61; 95% confidence interval [CI], 1.69, 4.03) if they were initially admitted with OC. Survival times for different stages of disease showed the best between-stage distinction for a Scheme ORAL, with the OC stage having a median survival of 643 days. Mean days of hospitalization also showed best distinctions for Scheme ORAL. Other staging schemes did not distinguish patients as well in terms of both survival times or mean hospitalization days. HIV-infected patients admitted with OC but without AIDS had a discrete survival prognosis and hospitalization course. Therefore, presence of OC even without other immunologic data has implications for institutional resource allocation and planning. These data support, in this context, a separate clinical designation for OC patients. PMID- 8506896 TI - The order of dilator-constrictor administration affects stenotic hemodynamic responses. AB - This study tested the hypothesis that, due to intraluminal pressure changes, the order of constrictor-dilator administration alters stenotic hemodynamic responses. Canine carotid arteries were perfused with a physiologic salt solution under constant pressure (100 mm Hg). An intraluminal stenosis partially obstructed the arteries. Pressures proximal and distal to the artery and the flow were continually recorded as norepinephrine (10(-9)-10(-6) M) was added to the perfusate. Adding diltiazem (10(-7) M) before norepinephrine shifted the effective half maximum dose (ED50) of the norepinephrine flow curve from 7.35 +/- 0.66 X 10(-8) M to 6.39 +/- 0.72 X 10(-7) M (p < 0.05). More important, adding 10(-7) M diltiazem after norepinephrine-induced constriction did not reestablish stenotic pressure or flow: A 30-fold increase in diltiazem concentration (3.16 X 10(-6)M) was required to reestablish stenotic pressure (62.6 +/- 4.4 mm Hg) and flow (25.4 +/- 3.2 ml/min). Similarly, adding nitroglycerin (10(-7) M) before norepinephrine shifted the ED50 from 7.21 +/- 0.58 X 10(-8) to 5.94 +/- 0.78 X 10(-6) (p < 0.05). Adding 10(-7) M nitroglycerin after norepinephrine did not reestablish stenotic pressure or flow: 3.16 X 10(-6) M nitroglycerin was required to reestablish stenotic pressure (59.2 +/- 4.8 mm Hg) and flow (23.2 +/- 2.7 mL/min). This constrictor-dilation history did not occur in isolated arterial rings (norepinephrine + nitroglycerin = 38.1 +/- 13.9 g/cm2; nitroglycerin + norepinephrine = 42.2 +/- 9.4 g/cm2; p = not significant [NS]) or in normal arteries (norepinephrine + nitroglycerin = 4.89 +/- 0.14 mm [external diameter]; nitroglycerin + norepinephrine = 4.92 +/- 0.23 mm; p = NS). In stenotic arteries, intraluminal pressure influenced the order of constrictor-dilator administration on hemodynamic response, which was not observed in isolated arterial rings or in normal arteries. This pressure-dependent sensitivity affects vasomotor tone and may be important in the pathophysiology of ischemia. PMID- 8506897 TI - Ambulatory blood pressure measurements in children and young adults selected by high and low casual blood pressure levels and parental history of hypertension: the Bogalusa Heart Study. AB - Ambulatory blood pressure measurements were obtained in 57 children and young adults selected by prior high or low casual blood pressure levels and parental history of hypertension. Considerable variation in blood pressure levels occurred over 24 hours, with generally higher levels occurring in those so selected. Parental history had a small influence on higher levels, although statistical significance was not shown. Persons with higher blood pressure levels did not reach levels as low during sleep, especially with regard to the systolic measurement, and a greater variability was noted in those selected for higher levels. Although differentiation of persons with high and low blood pressure levels can be obtained by noting average levels persisting above a cut point, for example, 140/85, in growing children an arbitrary 90th percentile based on age, height, and weight may be more appropriate. Ambulatory monitoring showed that young persons, selected by casual measurements as having high blood pressure, have a greater percentage of high levels persisting over a 24-hour period, comprising a greater blood pressure load. These observations also showed that even two series of casual measurements may misclassify a person as having hypertension. Ambulatory blood pressure monitoring will enhance understanding of the early natural history of hypertension and allow improved prevention of the disease. PMID- 8506898 TI - Clinical and sociocultural determinants of gallstone treatment. AB - Cholecystectomy remains the principal treatment for gallstones. Many gallstone patients do not undergo surgery within 6 months of diagnosis. To determine factors associated with cholecystectomy, treated and untreated patients were compared with respect to clinical and sociodemographic factors. The study population was comprised of outpatients of a public system evaluated in an emergency room or at a community health center. All were interviewed in English or Spanish before completing imaging studies. Of 121 found to have gallstones, 75 underwent early cholecystectomy. Patients reporting episodes of prolonged abdominal pain more often had surgery (p < 0.003). Patients evaluated in the emergency room underwent surgery more often than those from the community health center (p < 0.04). Patient ethnicity was unrelated to treatment, but Mexican Americans who requested interviews in Spanish were less likely to undergo cholecystectomy (p < 0.05). After logistic regression, prolonged abdominal pain was the only significant predictor of surgical management, although relationships with language use and site of diagnosis persisted. It was concluded that clinical presentation largely determines surgical treatment for gallstones but site of diagnosis is also a factor. Patients with poor English language skills undergo cholecystectomy less often. This may be due to poor doctor-patient communication, or it may be a reflection of cultural factors linked to language use. PMID- 8506899 TI - Case report: phaeohyphomycosis due to Curvularia lunata involving skin and subcutaneous tissue after an explosion at a chemical plant. AB - Cases of phaeohyphomycosis due to dematiaceous fungi have been reported in increasing numbers and diversity. The optimal roles of antifungal chemotherapy and surgical debridement in the management of these infections have not been determined. A case of acute cutaneous and subcutaneous phaeohyphomycosis due to Curvularia lunata after an explosion at a chemical plant is reported, in which the organisms may have been inoculated into the tissues by the force of the blast. No organisms were found by histopathologic examination or culture of excisional biopsy specimens taken 10 days after initiation of therapy with intravenous amphotericin B; the antifungal therapy may have eradicated the infection. PMID- 8506900 TI - Case report: acute postoperative respiratory failure caused by Chlamydia pneumoniae and diagnosed by bronchoalveolar lavage. AB - Most Chlamydia pneumoniae infections are mild, but 10% develop into pneumonia. C. pneumoniae has been observed in hospital in intubated patients undergoing major surgery or admitted with severe trauma. A patient with squamous cell carcinoma in whom severe pneumonia developed postpneumonectomy and who required mechanical ventilation is presented. The patient was initially treated for nosocomial bacterial pneumonia with the broad spectrum antibiotics ceftazidime, amikacin, and vancomycin. The patient underwent a bronchoalveolar lavage, from which C. pneumoniae was grown. Generally, these patients are a high-risk mortality group. Only after substituting the above antibiotics with doxycycline, to which C. pneumoniae was sensitive, did the pneumonia respond. Whether this was a nosocomial or a community-acquired pneumonia is uncertain. PMID- 8506901 TI - Respiratory muscles and ventilatory failure: 1993 perspective. AB - Some conditions that predispose to ventilatory failure increase the work of breathing (chronic obstructive pulmonary disease [COPD], obesity, kyphoscoliosis), whereas others cause severe respiratory muscle weakness. Specific reasons for muscle weakness include critical illness (electrolyte imbalance, acidemia, shock, sepsis), chronic illness (poor nutrition, cachexia), and neuromuscular diseases. Inspiratory muscle weakness from mechanical disadvantage to the diaphragm is characteristic of asthma and COPD. The increased work of breathing combined with muscle weakness increases the pressure needed to inspire a breath and decreases maximal inspiratory pressure. When this pressure exceeds 0.4, dyspnea and inspiratory muscle fatigue ensue. One way to lower this pressure and avert fatigue is to lower the tidal volume. Ventilatory drive is high, not low, in ventilatory failure. Concomitant shortening of inspiration and breath duration cause the small tidal volume and increased respiratory rate. Gas exchange is compromised by ventilation/perfusion imbalance, and the ratio of dead space to tidal volume is also increased by rapid, shallow breathing. Reduction in tidal volume minimizes dyspnea, but the small tidal volume is inadequate for gas exchange. Acute treatment of respiratory muscle failure involves respiratory muscle rest through mechanical ventilation and removal of noxious influences (infection, metabolic disarray), whereas chronic treatment involves rebuilding the contractile apparatus by nutritional repletion and training. PMID- 8506902 TI - Newer agents for the treatment of malignant hypercalcemia. AB - The treatment of malignant hypercalcemia has involved fluids, diuretics, and specific calcium-lowering therapy with mithramycin and calcitonin. However, newer agents have recently been approved for the treatment of hypercalcemia due to malignancy. This review will discuss three such agents, gallium, etidronate, and pamidronate. This review will concentrate on the clinical pharmacologic characteristics and the clinical trials of these newer agents. Their use in the clinical practice will be suggested based on review of the published literature. PMID- 8506903 TI - The arts of war and medicine: a study in symbiosis. AB - Practitioners of warfare and medicine have both considered their respective disciplines part art and part science. Each has seen dramatic advances over the past several centuries, and the histories of progress in warfare and medical practice are inextricably intertwined. For example, the congregation of large armies inspired the development of epidemiologic analysis and preventive medicine, which forestalled the disastrous loss of life that typified all wars through the U.S. Civil War. Warfare also helped to clarify the critical distinction between medicine and health in several ways. Battles generate tremendous demands on the trauma surgeon, which triggers advances in understanding of trauma, surgery, fluid and electrolyte management, first aid, and triage. Similarly, the health of soldiers before and after combat is a result of public health measures that physicians have been ill-suited to manage. The dramatic severity of epidemics in armies progressively forced health professionals and politicians to seek solutions to illnesses that had plagued the general population to lesser degrees for millennia. The exigencies of war inspired creation of the nursing profession, with the burden and opportunity falling on women. Women were not allowed to hold positions of responsibility in caring for the sick until the enormity of the Civil War prevented men from occupying all such positions. Because each generation tends to view itself as "modern," its inherent weaknesses often go uncorrected and even unobserved. The interconnected histories of war and medicine provide a warning to remain open to discovering those practices that need radical reform to prevent the current generation of physicians from appearing utterly ridiculous to physicians 100 years hence. This treatise focuses, therefore, on the symbiotic advances in warfare on health before this century because death in war due to trauma was statistically far less important than death due to disease. PMID- 8506904 TI - Prevalence of pigment dispersion syndrome in a population undergoing glaucoma screening. AB - The prevalence of pigment dispersion syndrome is thought to be relatively uncommon. Extrapolation of prevalences from glaucoma practices would suggest about 25,000 to 220,000 persons in the United States, an order of magnitude spread. By performing two population screenings that included slit-lamp examination, we detected pigment dispersion syndrome in 18 of 934 individuals. Sixteen of these were white, so that the prevalence of pigment dispersion syndrome in this group was 2.45%. We suggest that many more persons than previously believed may be at risk to develop pigment dispersion. PMID- 8506905 TI - Glaucoma in the immediate postoperative period after penetrating keratoplasty. AB - In a prospective study 155 consecutive patients undergoing penetrating keratoplasty were examined for postoperative increase in intraocular pressure to determine the frequency and duration of intraocular pressure spikes, risk factors, and response to treatment. Patients were maintained on preoperative glaucoma medications except miotics. Additional medications to lower intraocular pressure perioperatively were not given. Intraocular pressure was measured two to five hours, one day, and one week postoperatively. An intraocular pressure of 30 mm Hg or greater was considered an increase in pressure and was treated according to a standardized protocol. The results were analyzed by procedure as well as by variables commonly perceived to be associated with intraocular pressure increase (history of glaucoma, use of hyaluronate, lysis of the synechiae, or vitrectomy at the time of the operation). Overall, intraocular pressure increases in the early postoperative period occurred in 18 of 155 patients (12%). Pressure increases occurred in ten of 48 patients (21%) with a history of glaucoma; five of 24 patients (21%) undergoing combined penetrating keratoplasty, extracapsular cataract extraction, and posterior chamber intraocular lens implantation; and ten of 43 patients (23%) undergoing vitrectomy at the time of penetrating keratoplasty. PMID- 8506906 TI - Postkeratoplasty astigmatism with single running suture or interrupted sutures. AB - In a prospective randomized clinical trial we compared astigmatism after penetrating keratoplasty with two different suture techniques between two groups of patients (38 patients). The first group (18 patients) had a 24-bite single running 10-0 nylon suture (single running suture) with postoperative suture adjustment to decrease astigmatism. The second group (20 patients) had a combination of a 16-bite running 10-0 nylon suture and eight interrupted 10-0 nylon sutures (combined running and interrupted sutures) with selective postoperative removal of interrupted sutures to decrease astigmatism. The single running suture resulted in a lower postoperative astigmatism than a combined running and interrupted suture technique (single running suture, 2.7 +/- 2.2 diopters; combined running and interrupted sutures, 3.9 +/- 2.5 diopters; P < .02). Average length of follow-up was similar in both groups (single running suture, 9.0 +/- 2.2 months and combined running and interrupted sutures, 8.4 +/- 2.2 months). Minimal length of follow-up was six months in both groups. No running sutures were broken. The adjustable single running suture technique provided greater control of astigmatism after penetrating keratoplasty than a technique using a combination of a 16-bite running suture and eight interrupted sutures. PMID- 8506907 TI - Clinical findings in Brown-McLean syndrome. AB - The Brown-McLean syndrome is a clinical condition with corneal edema involving the peripheral 2 to 3 mm of the cornea. The edema typically starts inferiorly and progresses circumferentially, but spares the central portion of the cornea. Additionally, the edema is associated with a punctate orange-brown pigmentation on the endothelium underlying the edematous areas. Central cornea guttata is frequently seen. This condition occurs most frequently after intracapsular cataract extraction, but may also occur after extracapsular cataract extraction and phacoemulsification, or pars plana lensectomy and vitrectomy. Surgical complications and multiple intraocular procedures are frequently observed in these patients. Less frequently, the Brown-McLean syndrome can occur in eyes that have not had surgery. We studied the clinical characteristics of 43 affected eyes of 32 patients. New findings included Brown-McLean syndrome occurring in two eyes of a phakic patient with intermittent angle-closure glaucoma. Two eyes developed Brown-McLean syndrome after phacoemulsification and one eye developed peripheral edema after pars plana vitrectomy and lensectomy. Additionally, severe, infectious keratitis occurred after rupture of peripheral bullae in two eyes. Patients with this condition should be examined periodically and educated regarding the early clinical signs of corneal ulceration. PMID- 8506908 TI - Gadolinium magnetic resonance imaging dacryocystography. AB - A 1:100 solution of 48% gadopentolate in liquid tear solution was used in magnetic resonance dacryocystography to image the canaliculi, nasolacrimal sac, and nasolacrimal duct. It was administered as an eyedrop, one drop every minute for five minutes, immediately before scanning in six normal and five abnormal nasolacrimal outflow systems. In cases of nasolacrimal obstruction, the dilute gadolinium solution was injected through the canaliculus immediately before scanning. A three-inch surface coil enhanced the detail of soft-tissue structures such as the canaliculi and lacrimal sac. In the evaluation of complex tearing disorders such as congenital, neoplastic, postsurgical, and posttraumatic nasolacrimal obstruction, gadolinium lacrimal contrast adds useful information to magnetic resonance images of the lacrimal outflow system. Because of the expense of the test, we do not recommend it as a routine examination. PMID- 8506909 TI - Progressive ocular toxoplasmosis in patients with acquired immunodeficiency syndrome. AB - We studied two patients, a 43-year-old Hispanic man with a one-year history of acquired immunodeficiency syndrome (AIDS) and a 34-year-old Hispanic man with newly diagnosed AIDS. Both had necrotizing retinitis that progressed to panophthalmitis and orbital cellulitis. Toxoplasmosis was not diagnosed in the first patient early in the course of the disease. The second patient had a history of toxoplasmic retinochoroiditis. Despite anti-toxoplasmosis therapy, visual acuity deteriorated to no light perception in both patients. Diagnostic biopsy of the eye wall was performed on the first patient and enucleation of the globe on the second. Toxoplasmic panophthalmitis and orbital cellulitis were diagnosed in each patient by light microscopy and confirmed by electron microscopy. When patients with AIDS develop necrotizing retinitis, toxoplasmosis must be considered in the differential diagnosis, along with cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis. Unlike cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis, however, toxoplasmosis can cause a progressive intraocular infection, panophthalmitis, and orbital cellulitis in patients with AIDS. PMID- 8506910 TI - Drainage of subretinal fluid with the argon laser. AB - We performed 115 scleral-buckling procedures for primary rhegmatogenous retinal detachments in which the argon endolaser drained subretinal fluid. The laser was set at 0.80 to 1.25 W and 0.5 second; the endolaser probe was held adjacent to, but not touching, the choroid. The procedure was successful in 112 of 115 (97.0%) patients. When inadequate drainage occurred, the use of the penetrating diathermy tip was successful. The only major complications were subretinal hemorrhages that had migrated posterior to the buckle in two patients (1.70%), retinal perforation in one patient (0.87%), and retinal incarceration in one patient (0.87%). Laser drainage caused a slow, controlled drainage of subretinal fluid. PMID- 8506911 TI - Laser scleral buckling for retinal reattachment. AB - The holmium:yttrium aluminum garnet (Ho:YAG) laser produces infrared light that is absorbed inside scleral tissues, which increases local temperature, thereby shrinking collagen and inducing a buckle effect. Scleral indentation was induced in ten cadaver eyes by shrinkage of scleral collagen fibers by using a pulsed solid-state Ho:YAG (2.1-microns) laser with fiberoptic delivery. The amount of laser-induced buckling effect is controlled by selecting laser treatment settings such as beam spot, radiant exposure, and number of pulses. With treatment using 11.3 +/- 1.2 J/cm2 of laser radiant exposure and five pulses, laser-induced scleral shrinkage affected only the external two thirds of the scleral tissue. No thermal damage or disruption was observed in subjacent retinal pigment epithelium, choroid, or retina. The coupling of two appropriately selected lasers may allow laser-induced scleral buckling and transscleral retinal photocoagulation by using the same laser probe for retinal reattachment. PMID- 8506912 TI - Effects of inflammation and surgery on amikacin levels in the vitreous cavity. AB - Intraocular injection of amikacin is increasingly used in the treatment of endophthalmitis. We injected 400 micrograms of amikacin into the vitreous cavity of rabbit eyes to study its pharmacokinetics. Phakic, aphakic, and aphakic vitrectomized eyes were injected, and inflamed eyes were compared to control eyes. Vitreous concentrations were determined at two, eight, 24, and 48 hours, and clearance rates were calculated. Amikacin is cleared considerably more quickly from aphakic (half-life, 14.3 hours) than phakic control eyes (half-life, 25.5 hours) and even more quickly from aphakic vitrectomized eyes (half-life, 7.0 hours). Inflammation substantially increased the rate of clearance in aphakic eyes. In inflamed aphakic and aphakic vitrectomized eyes, vitreous drug levels were equal to or below the minimal inhibitory concentration for most organisms considered sensitive to amikacin at 24 hours. Supplementation of intraocular antibiotics may therefore be required in clinical settings. PMID- 8506913 TI - The effect of pentoxifylline on retinal capillary blood flow velocity and whole blood viscosity. AB - Ten normal, healthy, nonsmoking volunteers participated in a double-masked, placebo-controlled one-day trial of 2,000 mg of oral pentoxifylline to determine the short-term effects of orally administered pentoxifylline on retinal circulation and rheologic properties of whole blood. Retinal capillary blood velocity and leukocyte density, whole blood viscosity, and whole blood filterability were measured before and after therapy by the blue-field entoptic phenomenon computer simulation, rotational viscometry, and micropore filtration techniques, respectively. Treatment with pentoxifylline for one day resulted in a significant improvement in retinal capillary blood flow velocity (P = .02) and in viscosity (P < .01), but not filterability, of whole blood. These results suggest that pentoxifylline may be useful in the treatment of early diabetic retinopathy. PMID- 8506914 TI - Visual loss complicating OKT3 monoclonal antibody therapy. AB - OKT3 is a murine monoclonal antibody used for immunosuppression of solid-organ transplant rejection. We studied severe visual loss after administration of OKT3 in two patients who received renal transplants (one 25-year-old woman with interstitial nephritis and severe hypertension and one 27-year-old woman with diabetic nephropathy). Both patients lost visual acuity to the level of light perception after a second or third dose of OKT3. Ophthalmoscopy disclosed arteriolar constriction, but there was no evidence of optic atrophy. The electroretinogram was extinguished in one patient, indicating an effect on the outer retina or retinal pigment epithelium. Ophthalmologists should be aware that OKT3 may cause profound visual loss in patients who receive organ transplants. PMID- 8506915 TI - Conjunctival biopsy in scleroderma and primary Sjogren's syndrome. AB - Keratoconjunctivitis sicca complicates both scleroderma and Sjogren's syndrome. Scleroderma of recent onset is difficult to diagnose, but is easily recognized late in its course. To assess the value of the conjunctival biopsy in the diagnosis of scleroderma, we used light, scanning, and transmission electron microscopy to compare in a masked fashion specimens from 21 patients with scleroderma and 14 patients with primary Sjogren's syndrome. Epithelial changes permitted diagnosis of early scleroderma in the two groups of patients. Lymphocytic infiltrate was always present in Sjogren's syndrome, but not in scleroderma. Fibrosis was always found in scleroderma, even in scleroderma of recent onset, but was absent in Sjogren's syndrome. The fibrosis was distributed around capillaries in a band-like pattern and was associated with degranulating mast cells. Conjunctival biopsy is valuable for the early diagnosis of scleroderma and for differentiating between scleroderma and primary Sjogren's syndrome. PMID- 8506916 TI - Nucleolar organizer regions in determining malignancy of pigmented conjunctival lesions. AB - We assessed the usefulness of silver staining of nucleolar organizer regions in the diagnosis of pigmented conjunctival tumors. Fifty-one biopsy specimens were silver stained to identify the nucleolar organizer regions. Nineteen nevi without atypia, three nevi with atypia, eight primary acquired melanosis lesions, and 14 melanomas were studied. In each specimen, silver staining of the nucleolar organizer regions was counted in 100 cells to yield an average of the silver staining of the nucleolar organizer region count. The mean silver staining of the nucleolar organizer region counts per cell was correlated with the degree of malignancy of pigmented conjunctival lesions as follows: nevi, 3.0; primary acquired melanosis, 3.2; nevi with atypia, 3.9; primary acquired melanosis with atypia, 5.0; and melanoma, 5.7 (Spearman correlation [rS] = .83, P = .0001; analysis of variance [ANOVA] F test = 20.9, P = .0001). A cutoff value of 4.0 (mean silver staining of nucleolar organizer regions per cell) will differentiate melanoma and primary acquired melanosis with atypia from other lesions (sensitivity, 100%; specificity, 96%). The silver staining of nucleolar organizer regions is a useful adjunct in determining the malignancy of pigmented conjunctival tumors. PMID- 8506917 TI - Another reevaluation of combined cataract and glaucoma surgery. PMID- 8506918 TI - Blood dyscrasias and topical ophthalmic chloramphenicol. PMID- 8506919 TI - Transient myopia, angle-closure glaucoma, and choroidal detachment after oral acetazolamide. PMID- 8506920 TI - Systemic antibiotic therapy for relapsing Haemophilus influenzae conjunctivitis. PMID- 8506921 TI - An illuminated cannula for subretinal operations. PMID- 8506922 TI - Indocyanine green choroidal videoangiography during induced intraocular hypertension. PMID- 8506923 TI - Partial-thickness scleral-patch graft in revision of trabeculectomy. PMID- 8506924 TI - Reduction of subepithelial haze after photorefractive keratectomy by cooling the cornea. PMID- 8506925 TI - Refractive changes with increasing altitude after radial keratotomy. PMID- 8506926 TI - Eikenella corrodens canaliculitis. PMID- 8506927 TI - Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation. PMID- 8506928 TI - Causes of reduced visual acuity on long-term follow-up after cataract extraction in patients with uveitis and juvenile rheumatoid arthritis. PMID- 8506929 TI - Competency: ethical issues and dilemmas. PMID- 8506930 TI - Perceiving patients and their nonverbal reactions. AB - The topic of interest underlying the present study concerns cognitive and conceptual development in adulthood. Specifically, we examined the ways in which professional education affects occupational therapy students' perceptions and descriptions of patients' nonverbal behavior. Thirteen subjects viewed 3 videotapes of patients in treatment and then described the patients' responses. They viewed the videotapes twice, at the beginning of student training and one and a half years later. Results indicated that at the second viewing, the subjects' accounts became more differentiated, more complex, and less conclusive. Also on the second viewing, subjects were more likely to corroborate their inferences concerning patients' emotional reactions with concrete observations, but did not describe patients in common theoretical categories. This result indicates that subjects find it difficult to discuss individual cases in relation to newly acquired theoretical knowledge. We conclude that, rather than increased instruction in theory, students need increased opportunity to analyze individual cases by means of theoretical knowledge. PMID- 8506931 TI - A comparison of the grip strength of children with myelomeningocele to that of children without disability. AB - The grip strengths of 108 children aged 6 to 19 years with myelomeningocele were measured and compared with previously published results for children without disability. The grip strengths of the 59 female subjects with myelomeningocele were significantly lower than those of the population without disability in all age groups except for the 12 to 15 years range. The 49 male subjects exhibited significantly lower grip strengths only up to age 12 years. Implications and recommendations for clinical treatment, effects of secondary neurological complications, limitations of the study, and topics of future research are discussed. PMID- 8506932 TI - Occupation and the relevance of primatology to occupational therapy. AB - The adaptive functions of occupation during the phylogenetic history of the human species and the ontogenetic development of individual primates re examined through a review of relevant research of wild and captive nonhuman primates. This review suggests that the effectiveness of occupation as a therapeutic medium throughout life span development is fundamentally tied to humankind's phylogenetic history. It is accordingly argued that there is considerable justification to maintain occupational therapy's historical commitment to therapeutic occupation as the profession's primary treatment modality. To support this commitment, questions to guide practice and research are identified that emanate from the primate literature and that are highly germane to the therapeutic process in occupational therapy. These questions address: (a) the relationship between the press of the various environments in which occupational therapists practice and subsequent opportunities availed to patients for engagement in occupation; (b) the relationship between the extent to which patients are or are not empowered to exert real control over their use of time and their eventual development of disabling conditions; and (c) the therapeutic efficacy of occupation as compared with other treatment approaches that are not comparably holistic. PMID- 8506933 TI - Handwashing practices among occupational therapy personnel. AB - Handwashing is the most effective method of preventing the spread of nosocomial infection. Despite its simplicity, handwashing is frequently omitted by health care personnel. To date there have been no studies of the handwashing practices of occupational therapists. A telephone survey of 50 occupational therapy personnel indicated that the majority (60%) washed their hands with a liquid antimicrobial soap 9 or more times during the work day with a wash duration of 10 seconds or less. Analyses revealed no statistically significant differences between handwashing frequency and duration and age, years in practice, position, academic degree, or work setting. Overall, handwashing technique was found to be lacking. All respondents stated that handwashing was important to occupational therapy practice and most agreed that it was just as important for therapists as it was for physicians and nurses. Most agreed that hands should be washed both before and after each patient contact. However, few respondents actually did so regularly. Most respondents indicated that they received their knowledge of handwashing from inservice training at their place of employment. Their occupational therapy educational programs did not provide basic information on handwashing techniques. PMID- 8506934 TI - The influence of an animal on social interactions of nursing home residents in a group setting. AB - This study was conducted to determine the effect of the presence and absence of a dog on the frequency and types of social interactions among nursing home residents during a socialization group. Point sampling was used to evaluate the behaviors of 36 male nursing home residents at a Veterans Administration Medical Center under two conditions, Dog Present and Dog Absent. A significant difference in verbal interactions among residents occurred with the dog present, F(1, 69) = 4.92, p < .05. These findings are consistent with existing literature, thus providing further evidence of the value of Animal Assisted Therapy programs as an effective medium for increasing socialization among residents in long-term care facilities. Because an increase in social interactions can improve the social climate of an institution and occupational therapists frequently incorporate group process into their treatment, the therapeutic use of animals can become a valuable adjunct to reaching treatment goals. PMID- 8506935 TI - Student coping strategies and perceptions of fieldwork. AB - A questionnaire, the revised Ways of Coping Checklist, was sent to all professional (entry-level) graduate students in the United States in one academic year during their second fieldwork level II experience to determine what coping strategies they used during their fieldwork experience. Information was also gathered regarding their perceptions of this clinical experience. Responses from 101 students showed that they used Problem-Focused and Seeks Social Support strategies more than Wishful Thinking, Blamed Self, or Avoidance strategies. More than half of the students found the experience to be stressful, and almost all agreed that it was important. Most agreed that they had control over their present circumstances in the fieldwork experience. PMID- 8506936 TI - Student perceptions of persons with psychiatric and other disorders. AB - Policy shifts toward fostering community inclusion of persons with disabilities have brought community attitudes (including attitudes of professionals) into sharper focus as a cause for concern. Using a social distance scale, this study examined the attitudes of cohorts of occupational therapy and business students toward persons with psychiatric and other disorders. Contrary to expectations, occupational therapy seniors did not demonstrate significantly different attitudes from occupational therapy freshmen. Although freshman occupational therapy students expressed a desire to maintain less social distance from persons with various disabilities than did freshman business students, there was nonetheless a hierarchy of preference for persons with certain disabilities over others. This order of preference had only weak stability between cohorts, with persons with psychiatric disabilities consistently ranking among the least favored. It is proposed that occupational therapy curricula attend to students' attitudes toward persons with psychiatric and other disabilities. To this end, certain strategies to enrich students' education are suggested. PMID- 8506937 TI - Overcoming topographical orientation deficits in an elderly women with a right cerebrovascular accident. PMID- 8506938 TI - New pathways for psychosocial occupational therapists. PMID- 8506939 TI - American Occupational Therapy Association Accreditation Committee Reliability Study. AB - The purpose of the study was to augment the previous CAHEA and AOTA Commission on Education validity and reliability studies with a reliability study focused on the accrediting activity processes within AOTA in conjunction with CAHEA. The three objectives of the study were to establish (1) the internal consistency of AC, RAE, and AMA raters; (2) interrater reliability among AC, RAE, and AMA raters; and (3) accuracy of AC, RAE, and AMA raters. Overall, the RAE raters were most internally consistent in their ratings (.94), followed by the AC (.93), and the AMA (.88). Because many of the RAE raters have participated recently in the new AOTA accreditation orientation workshop, it is not unusual that their ratings would have the least variability and be so closely matched to those of the AC raters. On the basis of these results, the raters in this study (44.5% of the total population of raters) could be expected to be highly consistent as they evaluate Essentials that are usually in compliance, many times out of compliance, and those in-between. Interrater reliability among all raters for all five Essentials and all four decision points was established at .93 with percent agreement with absolute concordance. Interrater reliability among AC and RAE raters only achieved .95 percent agreement. As more data were available (i.e., at Decision 3 and Decision 4), rater concordance increased. By Decision 4, the most critical decision point because these data constitute the Report of On-Site Evaluation (ROSE), percent agreement ranged from .83 to .96 for all three rating groups, and .86 to 1.00 for the AC and RAE raters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506940 TI - Assessment of clonality in lymphoid proliferations. PMID- 8506941 TI - Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen. AB - Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues. PMID- 8506942 TI - Postmortem localization of HIV-1 RNA by in situ hybridization in lymphoid tissues of intravenous drug addicts who died unexpectedly. AB - The histopathological alterations in lymphoid tissues and the presence of human immunodeficiency virus (HIV-1) RNA were studied in 25 consecutive autopsies of seropositive, apparently asymptomatic, intravenous drug overdose victims without palpable lymphadenopathy. The majority of lymphoid tissues in a given person showed either a combination of follicular hyperplasia and fragmentation or a combination of involution and depletion. Individuals with involuted and depleted lymphoid tissues were significantly older than those individuals with hyperplasia and fragmentation of follicles. Lymph nodes from individuals with hyperplasia with or without fragmentation were slightly but significantly larger than control nodes from seronegative persons. In tissues from infected cases, HIV-1 RNA was demonstrated by in situ hybridization in 49% of follicular centers showing hyperplasia, 62% of hyperplastic fragmented follicles, and 66% of involuted follicles in a distribution of follicular dendritic cells. No signal was detected in tissues demonstrating follicular depletion or nodes from seronegative persons. Scattered inter- and intrafollicular lymphoid cells with positive signal were present only in nodal tissues with follicular hyperplasia without involution. Tonsils, inguinal, axillary, mediastinal, supraclavicular, mesenteric nodes, and spleen were positive for HIV-1 RNA in 78%, 76%, 67%, 65%, 58%, 50%, and 28% of cases, respectively, and the prevalence of positivity reflected the presence of follicles. We conclude that the clinically asymptomatic period of HIV-1 infection is characterized by pathological stages in lymphoid tissues that have distinct histological alterations and distribution of viral RNA. PMID- 8506943 TI - Expression of interleukin-2R alpha and interleukin-2R beta in Hodgkin's disease. AB - Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL 2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell lines. In addition, soluble IL-2R alpha molecules were demonstrated in the supernatants of three of these cultured cell lines. In primary tissues, IL-2R alpha and IL-2R beta were seen in some but not all cases. Staining was detected in Hodgkin and Reed-Sternberg and in lymphoid cells. There was a remarkable difference in the pattern of expression, in that IL-2R alpha- but not IL-2R beta-positive cells from HD patients were clustered in frozen sections. We conclude from these data that IL-2R expression might be involved in the biology of HD. PMID- 8506944 TI - Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques. AB - The production of cytokines by atheromatous plaque macrophages from human endarterectomy tissue was assessed in vitro by short-term cell culture and in situ by immunohistology. Macrophages were isolated from plaques of 14 patients undergoing carotid endarterectomy and 7 patients undergoing reconstructive procedures on atheromatous distal aortic and femoral arteries. Tumor necrosis factor (TNF) and interleukin 1 (IL-1) production by plaque macrophages and blood monocytes isolated concurrently from these patients was assessed. TNF release by macrophages from carotid plaques (0.39 +/- 0.12 ng/10(6) cells/24 hours) was significantly augmented compared to the release by corresponding blood monocytes (0.014 +/- 0.011 ng/10(6) cells/24 hours, P = 0.03), and by macrophages from noncarotid lesions (0.038 +/- 0.036 ng/10(6) cells/24 hours, P < 0.04). Cellular TNF expression by macrophages within carotid plaques was also more prominent than in noncarotid lesions. By contrast, IL-1 production by plaque macrophages from both carotid and noncarotid plaques was not augmented compared to blood monocytes, and only infrequent and low-intensity labeling for IL-1 was present on macrophages within plaques from either group. These results provide functional and immunohistological evidence for increased production of TNF but not IL-1 by activated macrophages, indicating local and selective augmentation of cytokine production within carotid plaques. This suggests that macrophages play an active role in the inflammatory response within atheromatous carotid plaques. PMID- 8506945 TI - Cytotoxic effector cell granules recognized by the monoclonal antibody TIA-1 are present in CD8+ lymphocytes in lymph nodes of human immunodeficiency virus-1 infected patients. AB - A novel monoclonal antibody (mAB) TIA-1, which recognizes a 15-kd granule associated protein of cytotoxic T lymphocytes and natural killer cells, has been applied to sections of lymph nodes with human immunodeficiency virus (HIV) induced lymphadenopathy (follicular hyperplasia and lymphocyte depletion). The protein recognized by this mAB induces apoptosis in permeabilized lymphocytes in vitro. While this mAB reacted with approximately 46% of paracortical CD8+ cells in control nodes, it reacted with 75% of such cells in HIV-induced follicular hyperplasia. Germinal centers of the control nodes contained few TIA-1 + cells; in follicular hyperplasia caused by HIV-1, almost all germinal center CD8+ cells were TIA-1 +. Both in the control nodes and in HIV-induced follicular hyperplasia the majority of TIA-1 + cells coexpressed CD45R0. A marked loss of CD8+TIA-1+ cells was seen in lymphocyte-depleted nodes of patients with AIDS. The loss of these cytotoxic T lymphocytes may have a significant impact on the progression of the disease. PMID- 8506946 TI - Simian immunodeficiency virus infection of the gastrointestinal tract of rhesus macaques. Functional, pathological, and morphological changes. AB - Gastrointestinal dysfunction and wasting are frequent complications of human immunodeficiency virus (HIV) infection. Nutrient malabsorption, decreased digestive enzymes and HIV transcripts have been documented in jejunal mucosa of HIV-infected patients; however, the pathogenesis of this enteropathy is not understood. Rhesus macaques infected with simian immunodeficiency virus (SIV) also exhibit diarrhea and weight loss; therefore, we investigated the use of this animal model to study HIV-associated intestinal abnormalities. A retrospective study of intestinal tissues from 15 SIV-infected macaques was performed to determine the cellular targets of the virus and examine the effect of SIV infection on jejunal mucosal morphology and function. Pathological and morphological changes included inflammatory infiltrates, villus blunting, and crypt hyperplasia. SIV-infected cells were detected by in situ hybridization in stomach, duodenum, jejunum, ileum, cecum, and colon. Using combined immunohistochemistry and in situ hybridization, the cellular targets were identified as T lymphocytes and macrophages. The jejunum of SIV-infected animals had depressed digestive enzyme activities and abnormal morphometry, suggestive of a maturational defect in proliferating epithelial cells. Our results suggest that SIV infection of mononuclear inflammatory cells in intestinal mucosa may alter development and function of absorptive epithelial cells and lead to jejunal dysfunction. PMID- 8506947 TI - Increased interleukin-1 beta and fibronectin expression are early features of the development of the postcardiac transplant coronary arteriopathy in piglets. AB - The mechanism causing intimal thickening in the postcardiac transplant coronary arteriopathy (PCTCA) is associated with interactions between inflammatory cells and vascular cells. Our previous studies related intimal thickening to fibronectin-dependent smooth muscle cell (SMC) migration into the subendothelium, and others have shown that cytokines, eg, interleukin (IL)-1 beta, up-regulate SMC fibronectin synthesis. In this study, we identified, in piglets, features compatible with early development of the PCTCA. Ultrastructure revealed increased SMC and inflammatory cells in the subendothelium. Immunohistochemistry showed major histocompatibility complex II presentation in the endothelium and adventitia, associated with infiltration of different subsets of inflammatory cells; increased IL-1 beta, particularly in the endothelium; and fibronectin, in the subendothelium and inner media, the latter confirmed by quantitative immunoelectron microscopy. In the PCTCA, increases in IL-1 beta and fibronectin could mediate adherence, transendothelial migration and trapping of inflammatory cells, and SMC migration into the subendothelium. PMID- 8506948 TI - Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection. AB - Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8+ and CD4+ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4+ CD45RA+, CD4+ CD45RO+, CD8+ CD45RA+, and CD8+ CD45RO+. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4+ CD45RA+ cells (median = 5.0 cells/HPF) relative to CD4+ CD45RO+ (3.12 cells/HPF), CD8+ CD45RA+ (2.14 cells/HPF), and especially CD8+ CD45RO+ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4+ CD45RA+ cells (6.67 cells/HPF, P < 0.09) and the greatest for CD8+ CD45RO+ cells (7.00 cells/HPF, P < 0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO+ to CD45RA+ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P < 0.008) and CD8 (1.43 versus 0.58, respectively; P < 0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA+ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO+ T cells, especially in the CD8 population. PMID- 8506949 TI - Renal apolipoproteins in nephrotic rats. AB - Recent experimental data suggest a role for lipids in the pathogenesis of glomerulosclerosis. In this study, we examined the main apolipoproteins (apo) of high density lipoproteins (A-I, A-IV, E), low density lipoproteins (B), and very low density lipoproteins (B,E) in plasma and kidney tissue of rats with puromycin aminonucleoside or adriamycin nephrosis. In full-blown nephrosis, plasma concentrations of apo A-I and apo B were significantly elevated, apo A-IV and apo E levels did not change. Immunohistological studies in plastic sections revealed increased apo A-I, apo A-IV, and apo E immunoreactivity in glomerular visceral epithelial cells both in puromycin aminonucleoside and adriamycin nephrosis. This was confirmed by immunoelectronmicroscopy. In addition, apo B and apo E were encountered in increased amounts in the mesangium and colocalized with Oil Red O positive lipid deposits, particularly in puromycin aminonucleoside nephrosis rats. Double-staining showed a preferential localization of apo B and apo E at sites of increased mesangial matrix in close proximity to ED1-positive foam cells, i.e., the mesangial macrophages. The close topographic association between apo B and apo E, lipid deposits, and macrophages in the mesangium lend further support to the concept of lipid-mediated glomerular injury in nephrosis. PMID- 8506950 TI - All-trans retinoic acid and extracellular Ca2+ differentially influence extracellular matrix production by human skin in organ culture. AB - Two-mm full-thickness punch biopsies of human skin were placed in organ culture in a serum-free, growth factor-free basal medium. Under conditions of low extracellular Ca2+ (0.15 mmol/L), the tissue quickly degenerated. However, degeneration was prevented when the extracellular Ca2+ concentration was increased to 1.4 mmol/L. The tissue remained histologically normal in appearance and biochemically active for up to 12 days. The addition of 3 mumol/L all-trans retinoic acid (RA) to the low-Ca2+ culture medium also prevented tissue degeneration. However, in contrast to what was seen in the presence of 1.4 mmol/L Ca2+, epidermal differentiation did not occur normally in the presence of RA. Rather, the upper layers of the epidermis routinely separated from the underlying basal cells. Fibronectin production by the organ cultured skin was examined. Biosynthetic labeling/immunoprecipitation studies demonstrated that incubation of the tissue in basal medium containing 1.4 mmol/L Ca2+ resulted in a high level of fibronectin production relative to the amount produced in basal medium containing 0.15 mmol/L Ca2+. In contrast, the addition of 3 mumol/L RA to the low Ca2+ basal medium did not stimulate fibronectin production. Similar results were observed in enzyme-linked immunosorbent assays where the addition of Ca2+ to a final concentration of 1.4 mmol/L stimulated fibronectin and thrombospondin production whereas RA (3 mumol/L) did not. Although RA by itself failed to stimulate extracellular matrix production, the addition of 3 mumol/L RA to basal medium containing 1.4 mmol/L Ca2+ led to a further increase in fibronectin production over that seen in the presence of 1.4 mmol/L Ca2+ alone. Taken together, these data indicate that although either 1.4 mmol/L Ca2+ or 3 mumol/L RA facilitates survival of organ-cultured skin in basal medium, they have very different effects on extracellular matrix production. This supports the view, based on histological appearance, that the two treatments work through different mechanisms. The data further support the suggestion that the two treatments may have additive or even synergistic effects. PMID- 8506951 TI - Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat. AB - Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes in vitro. The receptor for HGF has recently been characterized as the product of the proto-oncogene c-met. We have examined the possible involvement of HGF in hepatic growth and differentiation in the rat. The experimental systems used were acetylaminofluorene treatment combined with partial hepatectomy to induce proliferation and differentiation of oval cells in adult liver and the pre- and postnatal liver. In the acetylaminofluorene model, Northern blot analysis showed that level of HGF transcripts increased one day after partial hepatectomy, reached a peak by day 6, were maintained at that level until day 13, and then declined, reaching normal level at 20 days. The expression of c-met also increased gradually, reached a peak around 9 to 13 days after partial hepatectomy, at which time oval cell proliferation was most prominent. In the developing liver, an elevated level of HGF transcripts was found between 4 and 21 days after birth. The expression of c-met also slightly increased at the same time. In situ hybridization showed that the transcripts for HGF were localized in desmin-positive Ito cells, whereas the transcripts for c-met were strongly expressed by oval cells. We have shown earlier that Ito cells and oval cells proliferate simultaneously and exist in close proximity in the acetylaminofluorene model and that Ito cells are a primary source of growth factors such as transforming growth factor-alpha and acidic fibroblast growth factors. The data presented here suggest that HGF is, in combination with other growth factors, involved in the proliferation and differentiation of oval cells via a paracrine mechanism. PMID- 8506952 TI - Detection of clonal immunoglobulin gene rearrangements by polymerase chain reaction amplification and single-strand conformational polymorphism analysis. AB - Analysis of immunoglobulin gene rearrangements by Southern blotting is a sensitive and specific method for detecting B cell malignancies but requires a relatively large amount of intact DNA. It cannot be utilized in many cases where only a small amount of tissue is available or where the tissue has been fixed. This report demonstrates that polymerase chain reaction (PCR) amplification in conjunction with single-strand conformational polymorphism (SSCP) analysis can be utilized to detect clonal immunoglobulin heavy chain (IgH) gene rearrangements. IgH gene rearrangements from a series of frozen or formalin-fixed B cell malignancies were PCR-amplified using oligonucleotide primers, based upon consensus sequences in the IgH variable and joining regions. Analysis of the single-stranded PCR products on nondenaturing polyacrylamide gels revealed discrete SSCPs corresponding to the malignant B cells. These SSCPs were detectable when the malignant cells represented as few as 0.2% of the total mononuclear cells in peripheral blood. PCR amplification in conjunction with SSCP analysis thus provides a sensitive and specific method to detect clonal IgH rearrangements from minute amounts of fresh, frozen, or fixed tissue. PMID- 8506953 TI - Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis. AB - The complement C4-derived anaphylatoxin, C4a, possesses a strong chemotaxis inhibitory capacity to blood monocytes at concentrations as low as 10(-16) mol/L. In our study, treatment with carboxypeptidase B to convert it to C4a des Arg77 decreased the inhibitory activity to less than 1/1,000. The extraordinary inhibitory capacity of C4a suggests the presence of an amplification mechanism in this inhibition. Indeed, we found that the conditioned media of peripheral blood mononuclear cells or monocyte/macrophage lineage cell lines (U937 and THP-1 cells) preincubated with 10(-16) mol/L C4a for 5 minutes or more at 37 C possessed the inhibitory capacity 100,000-fold stronger than the original activity of C4a. The monocyte-derived chemotaxis inhibitory factor seemed monocyte-specific. This cell-derived factor was sensitive to treatment with trypsin and chymotrypsin and immunologically distinct from C4a. The apparent molecular size of the monocyte factor was estimated to be approximately 20 kd by gel filtration. These results indicate that C4a anaphylatoxin induces the release from monocytes of a protein with inhibitory activity for monocyte chemotaxis. PMID- 8506954 TI - Cellular localization of tumor necrosis factor (TNF)-alpha transcripts in normal bowel and in necrotizing enterocolitis. TNF gene expression by Paneth cells, intestinal eosinophils, and macrophages. AB - Tumor necrosis factor-alpha (TNF) has been shown to induce intestinal necrosis in animals. Moreover, plasma TNF levels are elevated in patients with necrotizing enterocolitis. Thus, it is possible that TNF plays a role in the pathogenesis of NEC. In the present study we used in situ hybridization (with human TNF riboprobes) to localize TNF transcripts in the intestinal tissues from normal biopsies and NEC patients. We found that in normal intestine a small amount of TNF mRNA was present only in Paneth cells. In contrast, in the acute stage of NEC, a high amount of TNF transcripts was detected in Paneth cells as well as in infiltrating eosinophils. In one case that showed infiltrating macrophages, TNF mRNA was also detected in these cells. Resident macrophages in the lamina propria and other inflammatory cells were negative for TNF transcripts. Our results suggest that: 1) Paneth cells are the major source of TNF transcripts in normal intestine, and 2) there is a marked increase in TNF mRNA formation in Paneth cells, as well as in infiltrating eosinophils and macrophages in patients with NEC. TNF-containing cells may play an important role in the pathophysiology of NEC. PMID- 8506955 TI - Human peritoneal mesothelial cells synthesize interleukin-8. Synergistic induction by interleukin-1 beta and tumor necrosis factor-alpha. AB - The present study demonstrates the synthesis and secretion of the neutrophil activating peptide/interleukin-8 (IL-8) by cultured human peritoneal mesothelial cells (HPMC) and examines the regulation of its production by other cytokines. Unstimulated HPMC under growth-arrested conditions released IL-8 in a constitutive and time-dependent manner. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time- and dose-dependent IL-8 generation; after 24 hours the levels induced by IL-1 beta and TNF-alpha (both at 1000 pg/ml) were (mean +/- SEM, n = 5) 101 +/- 26.6 (z = 2.023; P < 0.01) and 35 +/- 8.09 (z = 2.023; P < 0.01) respectively. This release was inhibited following coincubation with the relevant anti-cytokine antibody or preincubation with either cycloheximide or actinomycin D. Treatment of HPMC with IL-1 beta or TNF-alpha resulted in increased levels of IL-8-specific mRNA. Stimulation of HPMC with combinations of IL-1 beta and TNF-alpha resulted in a synergistic increase in IL-8 release. This effect was significant at combined doses of IL-1 beta (50 pg/ml) and TNF-alpha (500 pg/ml) and above, when the release of IL-8 was 88 +/- 27% above the additive IL-8 release values (z = 2.201; P < 0.01). Western blot analysis using specific anti-IL-8 antibody demonstrated the presence of two major immunoreactive bands between 9 and 10 kd, in HPMC culture supernatants. These data demonstrate that HPMC synthesize IL-8 and that its release can be regulated as a result of induction of mRNA expression and de novo protein synthesis by other cytokines. PMID- 8506956 TI - Beta/A4 proteinlike immunoreactive granular structures in the brain of senescence accelerated mouse. AB - The immunohistochemical localization of amyloid beta/A4 protein in the senescence accelerated mouse brain was studied using six different antisera against human amyloid precursor protein peptides. beta/A4 proteinlike immunoreactivity was observed in the form of granular structures (beta-LIGS) in various regions, including the medial septum, cerebral cortex, hippocampus, cerebellum, and some cranial nerve roots. beta-LIGS were 1.5 to 2.5 mu in diameter and irregularly shaped. They increased significantly in number with aging, predominantly in animals with a phenotype of age-related deterioration of memory and learning abilities. Congo red and thioflavine S did not stain the granules. On immunoblots, the main immunoreactive bands were observed at 14 to 18 kd. The staining intensities of these bands also increased with advancing age. We consider that beta-LIGS are not only a new morphological manifestation of senescence in mice, but also a pertinent clue in understanding the mechanisms of amyloid deposition. PMID- 8506957 TI - Chloroaluminum sulfonated phthalocyanine partitioning in normal and intimal hyperplastic artery in the rat. Implications for photodynamic therapy. AB - Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photosensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH; the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primarily the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy. PMID- 8506959 TI - Dendritic cells in the hearts of spontaneously hypertensive rats treated with doxorubicin with or without ICRF-187. AB - Histological and immunohistochemical studies using specific monoclonal antibodies were made to evaluate the severity of the chronic cardiomyopathy and the quantitative changes in interstitial dendritic cells (antigen-presenting cells), T helper lymphocytes, T cytotoxic/suppressor lymphocytes, and macrophages in the hearts of spontaneously hypertensive rats (SHRs) treated with doxorubicin at 1 mg/kg per week for 3, 6, 9 or 12 weeks. In addition, an assessment was made of the modifications of the responses of these cell populations by pretreatment of the SHR with ICRF-187, which protects against doxorubicin cardiotoxicity. The number of interstitial dendritic cells/mm2 of section of left ventricle was similar in saline-treated control SHRs (76 +/- 6) and in those treated with ICRF 187 alone (75 +/- 2) but increased markedly (319 +/- 33) in animals receiving a total cumulative dose of 12 mg/kg doxorubicin. Treatment with ICRF-187 prior to each administration of doxorubicin attenuated in a dose-dependent manner the increase in numbers of dendritic cells induced by doxorubicin (231 +/- 47, 174 +/ 11, and 100 +/- 16 cells/mm2) after treatment with 6.25, 12.5, and 25 mg of ICRF 187, respectively. Doxorubicin also induced increases in the numbers of T helper lymphocytes and macrophages but not of T cytotoxic/suppressor lymphocytes. These increases were also attenuated by pretreatment with ICRF-187. These data were interpreted as indicating that doxorubicin cardiotoxicity results in the release of substances that initiate immune reactions involving the antigen-presenting cells of the heart and that such reactions are attenuated by pretreatment with ICRF-187. PMID- 8506958 TI - Accelerated atherosclerosis in hyperlipidemic C57BL/6 mice treated with cyclosporin A. AB - We and others have demonstrated that T lymphocytes are prominent components of atherosclerotic lesions. We hypothesized that if T cells were necessary for the development of atherosclerosis it would be possible to demonstrate its prevention or retardation in T-cell-suppressed mice. To test this hypothesis, CyA, a potent suppressor of T-cell activation, was used to treat C57BL/6 mice undergoing lipid hyperalimentation. Mice receiving normal mouse chow were completely free of atherosclerotic lesions. In mice receiving the atherogenic diet plus control oil injections, lesions of the aorta and coronary arteries were observed at 135 days and increased progressively in area until 310 days. Somewhat surprisingly, mice given the atherogenic diet plus CyA injections displayed even larger lesions at all three observed time intervals. Although CyA did suppress T-cell reactivity sufficiently to obtain the expected prolongation of skin allografts, it did not suppress the development or progression of atherosclerotic lesions. PMID- 8506960 TI - Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. AB - Obliterative bronchiolitis, characterized histopathologically by airway inflammation and occlusion of small airways by vascularized fibrous tissue, constitutes an important threat to the long-term survival of lung and heart-lung transplant recipients. The pathogenesis of obliterative bronchiolitis is poorly understood, and successful preventative or treatment strategies are not available. We sought to develop a preclinical model system of obliterative bronchiolitis by transplanting murine airway grafts, consisting of tracheas and main bronchi, into the subcutaneous tissue of allogeneically mismatched recipient animals. By 10 days after transplantation, allografts demonstrated subepithelial and/or peritracheal inflammation, epithelial necrosis, and early fibroproliferation. Grafts harvested 21 days after transplantation demonstrated fibroproliferation in the airway wall or lumen in nine of 10 allografts versus 0 of 10 isografts (P = 0.0001). In addition, abnormal epithelium (ie, nonciliated cuboidal, squamous, or absent) was seen in all allografts, while nine of nine isografts demonstrated normal respiratory epithelium (P = 0.0003). Although differences exist between this model and the chronic rejection process in human lung transplant recipients, these findings reproduce the characteristic features of obliterative bronchiolitis and demonstrate that this lesion can result from allograft rejection. This model will be useful for studying the pathogenesis, prevention, and treatment of obliterative bronchiolitis after lung transplantation. PMID- 8506961 TI - Role of apoptosis in copper deficiency-induced pancreatic involution in the rat. AB - Rats maintained on a copper-deficient diet supplemented with a copper-chelating agent, triethylenetetramine tetrahydrochloride, for 8 to 10 weeks show marked involution of pancreatic acinar tissue. The present study deals with the possible mechanism of pancreatic acinar cell involution during copper deficiency. Sequential light and electron microscopic observations during the copper depletion regimen, suggest that apoptosis is the main cause of progressive loss of acinar cells. At 4 weeks of copper deficiency, the apoptotic index was 2 +/- 0.6/1,000 cells. By 6 weeks, the apoptotic index reached a maximum of 95 +/- 25/1,000. By 8 weeks, there was almost total loss of acinar cells. The earliest change of apoptosis was characterized by condensation and margination of chromatin against nuclear membrane. Subsequently, several apoptotic bodies displayed pyknotic nucleus and eosinophilic cytoplasmic condensation. Apoptotic bodies were extruded into the interstitium or phagocytosed by unaffected acinar cells. No associated pancreatic inflammation was present. These results indicate that apoptosis is the process involved in pancreatic involution caused by copper deficiency. The molecular mechanism(s) by which copper deficiency causes apoptosis remain unclear. PMID- 8506962 TI - Granuloma formation in severe combined immunodeficient (SCID) mice in response to progressive BCG infection. Tendency not to form granulomas in the lung is associated with faster bacterial growth in this organ. AB - Intravenous inoculation of Mycobacterium bovis, strain bacillus Calmette-Guerin caused infection in the lungs, livers, and spleens of severe combined immunodeficient (SCID) mice and in the same organs in immunocompetent co-isogenic C.B17 mice. However, whereas infection in the latter mice was stabilized and partly resolved, it was progressive in SCID mice and eventually lethal, with the most rapid bacterial growth occurring in the lungs. Histological examination of infected organs showed that well-developed, compact epithelioid granulomas formed at sites of bacterial multiplication in livers, spleens, and lungs of C.B17 mice. Granulomas also formed in the livers and spleens of SCID mice, despite their inability to generate immunity. However, in the lungs of SCID mice, bacillus Calmette-Guerin was regionally distributed mostly in isolated alveolar macrophages and in aggregates of macrophages resembling small granulomas. The possibility that this tendency not to form granulomas in the lung is the reason for the more rapid growth of bacillus Calmette-Guerin in this organ is discussed. PMID- 8506963 TI - Spectrum and management of major complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has become the most prevalent method of treating uncomplicated, symptomatic cholelithiasis in the United States and elsewhere. As experience with this procedure grows, certain pitfalls are becoming apparent. Since October 1990, we have treated 22 patients for major injuries incurred during laparoscopic cholecystectomy, including 15 women and 7 men (range: 23 to 85 years). One patient had previous upper abdominal surgery; no other patient had any relative contraindication to laparoscopic surgery. The most frequent site of injury (19 patients) was the extrahepatic biliary tract. There was one fatal duodenal perforation. All but two patients whose injuries went unrecognized at laparoscopy were symptomatic during the immediate postoperative period. The biliary injuries included complete transection of the common hepatic or common bile duct in 10 patients, complete ductal occlusion in 3, a cystic duct stump leak in 2, and a partially retained gallbladder with a contained intraperitoneal bile leak in 2. The site and extent of biliary injuries were delineated with transhepatic or endoscopic retrograde cholangiography. Reconstruction or repair of the biliary tract was accomplished with Roux-en-Y hepaticojejunostomy or cholangiojejunostomy in 11 and 1 patients, respectively, completion cholecystectomy in 2, and temporary transhepatic stenting, primary choledochocholedochostomy, and primary choledochorrhaphy over a T-tube in 1 patient each. One patient with a cystic duct stump leak was managed successfully with endoscopic sphincterotomy, whereas another required operative ligation. Laparoscopic injuries during cholecystectomy can lead to serious morbidity and mortality, thus emphasizing the need for adequate training and credentialing for surgeons and for a heightened clinical awareness of the potential complications, their long-term sequelae, and how to avoid them. PMID- 8506964 TI - Diagnosis and management of biliary complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has become the operation of choice for symptomatic cholelithiasis. However, this operation may result in serious biliary complications. Our aims were to review our experience with biliary complications of laparoscopic cholecystectomy and to document the mechanisms of the injuries and the techniques of managing these complications. We treated 20 patients with biliary complications of laparoscopic cholecystectomy. Symptomatic collections of bile (bilomas) were present in five patients. One of these patients underwent operative ligation of an accessory bile duct in the gallbladder bed, whereas the others had percutaneous or endoscopic therapy. In the remaining 15 patients (of whom 13 were referred from other hospitals), injuries to the major bile ducts were managed by combined radiologic, endoscopic, and operative therapies. In 10 of these patients (67%), the mechanism of injury was the misidentification of the common bile duct as the cystic duct. In 3 of 15 patients, a noncircumferential injury to the lateral aspect of the common bile duct occurred. The Bismuth levels of the remaining bile duct injuries were type I in 3, type II in 4, type III in 3, and type IV in 2. Early outcome of therapy for these bile duct injuries has been favorable. One patient was lost to follow-up, and 2 died of nonbiliary causes, whereas 12 patients are alive and well with normal serum liver enzyme levels at 4 to 19 months postoperatively (mean: 14 months). The most common cause of major bile duct injury during laparoscopic cholecystectomy is mistaking the common bile duct for the cystic duct. Most bilomas can be managed successfully with noninvasive methods. Coordinated efforts by radiologists, endoscopists, and surgeons are necessary to optimize the management of patients with major bile duct injury, suggesting that patients with biliary complications of laparoscopic cholecystectomy should be referred to specialty centers for optimal care. PMID- 8506965 TI - Laparoscopic versus traditional appendectomy for suspected appendicitis. AB - We compared the results of concurrently performed laparoscopic versus open appendectomy as treatments for suspected acute appendicitis. The 68 laparoscopic procedures resulted in 62 appendectomies, 47 by the laparoscopic (LA) technique and 15 by the open (LO) technique. Another 54 patients underwent open appendectomy (OA). Significantly more females underwent laparoscopy (LA and LO: 52% versus OA: 33%, p = 0.047). Operative duration was shortest for OA (81 +/- 3 minutes), which was shorter than for LO (108 +/- 7 minutes), but not different than LA (86 +/- 6 minutes). The postoperative length of stay was not different for LA (3.5 +/- 0.5 days) compared with OA (5.9 +/- 1.6 days) or LO (4.8 +/- 1.3 days). One death occurred in the OA group. Wound complication rates were not significantly different for LA (4.3%) compared with OA (9.4%) and LO (13.3%). Overall complication rates were lower for LA (10.6%) and OA (18.9%) compared with LO (46.7%, p < 0.01). Median hospital cost for LO ($10,425) was higher (p < 0.02) than for either LA ($5,899) or OA ($5,220). When appendicitis was not present, definitive confirmation of pathology was achieved in 9 of 18 patients undergoing LA versus 4 of 14 patients having OA (p = not significant). We conclude that when laparoscopy and laparoscopic appendectomy can be performed, the procedure is safe and produces results comparable with those of open appendectomy without significant overall cost differences. PMID- 8506966 TI - Small bowel myoelectric activity in peritonitis. AB - Peritonitis is associated clinically with paralytic ileus, but the physiologic mechanisms of the effects of peritonitis on bowel myoelectric activity have not been explored. Bipolar electrodes were inserted into the rats, and myoelectric control recordings were obtained for 4 h/d for 5 consecutive days. Peritonitis was then induced, and myoelectric recordings were again obtained. Each animal served as its own control. Prior to induction of peritonitis (control), phase I, II, and III myoelectric activity was present in all recordings. The cycle duration of the migrating myoelectric complex was 17.17 +/- 0.39 minutes, and the migration velocity of phase III was 0.61 +/- 0.02 cm/min. The most striking feature during peritonitis was the complete inhibition of phase II activity. Phase III activity, however, was present with a cycle duration of 16.69 +/- 0.42 minutes. This study shows that some features of intestinal myoelectric activity (phase III) are preserved during episodes of peritonitis, and others are changed (phase I) or lost (phase II). Disappearance of phase II activity in this type of ileus emphasizes its importance in normal small bowel motility. PMID- 8506967 TI - Motility differences between long-segment and short-segment Barrett's esophagus. AB - Barrett's esophagus has been described as a motility disorder of the esophagus, but the issue of whether or not the disorder precedes the columnar lining has been debated. Motility records of 70 patients with histologically proven Barrett's esophagus were analyzed. A comparison of the swallow responses was made between those patients who had a limited Barrett's segment (3 to 5 cm, n = 28) as opposed to those patients who had an extensive Barrett's segment (greater than 5 cm, n = 42). Patients with an extensive segment had a significantly lower amplitude (p < 0.01) of esophageal contraction and a significantly longer duration (p < 0.01) of contraction compared with patients with a limited segment. These differences were most marked in the distal esophageal segments. There was a progressive deterioration of esophageal motility with advanced disease. PMID- 8506968 TI - Adjunctive vasodilator therapy in the treatment of murine ischemia. AB - Potent vasoconstrictors such as angiotensin II and vasopressin have been implicated as mediators of persistent vasoconstriction after reversible superior mesenteric artery (SMA) occlusion. Neither captopril (CAP), an angiotensin converting enzyme (ACE) inhibitor, nor papaverine (PAP), a vasodilator, has proven effective in reversing this vasoconstriction when employed singly. The present study examined the combined effect of these agents in reducing mortality in a murine model of acute mesenteric ischemia. The SMAs of 106 adult male Sprague-Dawley rats were totally occluded for 85 minutes. Test agents were given intravenously at reperfusion over a 90-minute period. Survival rates were assessed at 48 hours. CAP was given as a single bolus (0.3 mg/kg) and PAP (0.5 mg/kg/h) as an infusion. Aortic and SMA blood flows were measured pretreatment and posttreatment in a separate group of 19 animals treated with CAP and PAP as single agents. chi 2 analysis and analysis of variance were used to test differences with p < or = 0.05 accepted as significant. PAP alone as an adjunct resulted in a significant increase in 48-hour survival (57% versus 19%, p < or = 0.005). PAP in combination with CAP produced the best outcome in this model (87% versus 19%, p < or = 0.005). Aortic blood flow decreased, whereas SMA blood flow increased after treatment both with CAP and with PAP, but not significantly. The combination of an intravenously administered vasodilator with either glucagon or an ACE inhibitor was the most effective adjunctive therapy in this mesenteric ischemia model. There was no evidence that an inotropic effect, rather than SMA vasodilation, was the responsible mechanism of action. PMID- 8506969 TI - Surgical decisions in the management of duodenal perforation complicating endoscopic sphincterotomy. AB - The management of duodenal perforation associated with endoscopic sphincterotomy is controversial. Despite the fact that many patients recover without surgery, surgical opinion tends to favor immediate operation upon diagnosis since the mortality is high when sepsis is advanced. To refine the criteria for operative management, all duodenal perforations after endoscopic sphincterotomy over a 5 year period were studied. In a series of 464 consecutive endoscopic sphincterotomies, 8 duodenal perforations occurred; additionally, 4 patients with duodenal perforation were referred from elsewhere for management. Six patients were managed initially with nonoperative treatment (group I), and six underwent exploratory surgery upon diagnosis or hospital transfer (group II). One patient in group I was operated on 4 days after diagnosis. Of the seven surgically treated patients, three had repair of the duodenal perforation and drainage of the abscess or phlegmon, but four had no gross inflammation or visible duodenal perforation requiring repair at exploration. The clinical features of abdominal pain with physical signs significantly correlated with operative findings of pus or phlegmon (p < 0.05). Improvement in symptoms within 24 hours is correlated with spontaneous recovery (p < 0.01). Neither the presence of retroperitoneal air nor contrast leak is predictive of the need for surgery, and neither correlated with the size of the perforation. It is concluded that duodenal perforation may be treated successfully without surgery when the symptoms are mild and improve rapidly with medical treatment, but surgery should be undertaken if pain and abdominal signs are prominent, if suppuration is suspected, or if symptoms do not improve after a brief period of nonoperative management. PMID- 8506970 TI - Site specificity and meal stimulation of the intestinal absorption of water, electrolytes, and bile acids. AB - Ileal water and electrolyte absorption exceed jejunal absorption in both the basal and meal-stimulated states. The purposes of these experiments were to determine: (1) if luminal bile acids alter basal or meal-stimulated intestinal absorption, and (2) if there is site specificity or meal stimulation of intestinal bile acid absorption. Twenty-five centimeters of canine proximal jejunal and distal ileal Thiry-Vella fistulas were constructed. Simultaneous jejunal and ileal absorption studies (n = 88) were performed with a luminal perfusate containing polyethylene glycol labeled with radioactive carbon-14 to calculate the absorption of water, electrolytes, and the bile acid taurocholate (TC). In group 1, there was no TC in the luminal perfusate, whereas in group 2, 10 mM of TC was present in the luminal perfusate. Half of the observations were performed after a meal stimulus, which consisted of an orally ingested, 480-kcal mixed nutrient meal. Intraluminal TC did not affect basal or meal-stimulated water or electrolyte absorption. In both the basal and meal-stimulated states, ileal absorption of water, electrolytes, and TC significantly exceeded jejunal absorption (p < 0.05). A meal significantly stimulated water and electrolyte absorption in both the jejunum and ileum, but it stimulated absorption of TC in the ileum only (p < 0.05). Intraluminal TC does not alter basal or meal stimulated intestinal water and electrolyte absorption. A meal stimulates increased water and electrolyte absorption in both the jejunum and the ileum, but it stimulates bile acid absorption in the ileum only. Bile acid absorption is site specific and responsive to a meal stimulus. PMID- 8506971 TI - Breast biopsy in women 30 years old or less. AB - Forty women 30 years of age or less underwent breast biopsy at Roswell Park Cancer Institute between January 1980 and January 1989. Thirty-eight of the 40 women had a palpable breast mass. Thirty-one of these young women had self detected breast masses, and the median duration before presentation was 6 months. Physical characteristics were described in 30 of the masses. Twenty-three were described as "fibroadenomas" or smooth, firm, and mobile. Seven masses were described as irregular. The median size of the breast mass was 1.5 cm (range: 0.5 to 9.0 cm). Mammography was performed in 20 patients, but results were reported as abnormal in only 6. Twenty of the masses were described histologically as fibroadenoma. Twelve were described histologically as "fibrocystic disease" or "stromal fibrosis." One case (2.5%) was invasive adenocarcinoma. Probability of serious underlying breast pathology in young women is low but not nil. Noninvasive and minimally invasive techniques are proposed by some authors as cost-efficient methods that may substitute for open biopsy in these patients. Unfortunately, false-negative results persist and are particularly unacceptable in these young women. During the same time period as our study, 54 women aged 30 years or less were referred to Roswell Park Cancer Institute with a previously diagnosed invasive breast cancer. The incidence of breast cancer in this biopsy series was 2.5%. The potential costs of misdiagnosed early breast cancer in young women negate any rationalization for less invasive biopsy techniques. Following aspiration to rule out a benign cyst, and a possible period of brief observation for spontaneous resolution (2 or 3 months), excisional biopsy is recommended for young women with a breast mass. PMID- 8506972 TI - Head and neck reconstruction using the platysma myocutaneous flap. AB - A retrospective analysis of our experience with 41 patients who received a platysma myocutaneous flap for reconstruction of intraoral and pharyngeal defects is presented. All patients had epidermoid carcinoma of the head and neck region, with tumor size ranging from T1 to T4. The primary sites of malignancy were the oral cavity (61%), the oropharynx (32%), and the hypopharynx (7%). Either radical or modified radical neck dissection requiring routine ligation of the facial artery was performed in all 41 patients. Adjuvant therapy included preoperative or postoperative radiotherapy (39%) and preoperative chemotherapy (73%). The mean hospital stay was 13 days. Flap-related complications occurred in eight patients (19%) only. These included partial flap necrosis involving the epithelium alone, skin necrosis of the neck suture line, and fistula formation. Most complications resolved with local care only. Minor surgical intervention was required in three patients. There were no perioperative deaths. These results indicate that the platysma myocutaneous flap is a viable alternative in head and neck reconstruction. PMID- 8506973 TI - Molecular biology and therapy of disease. AB - Molecular biology will have a profound impact upon the treatment of disease. Molecular techniques provide protein products for treatment of more diseases each year. The understanding of pathophysiology at the molecular level allows for improved drug design. Antisense technology can selectively control gene expression. Gene therapy is potentially the most important aspect of molecular biology. Physical and viral transduction mechanisms are being developed toward this end. Gene replacement, creation of antisense oligonucleotides, and prodrug strategies are being developed. Currently, gene replacement and prodrug therapy are feasible in at least a few cases, but further study will yield additional applications. PMID- 8506974 TI - Growth factors and wound healing: biochemical properties of growth factors and their receptors. AB - Wound healing is a complex biologic process that involves chemotaxis and division of cells, neovascularization, synthesis of extracellular matrix proteins, and remodeling of scar. Peptide growth factors have been shown to regulate many of these processes in vitro, leading to the hypothesis that peptide growth factors also regulate important phases of wound healing in vivo. Part I of this two-part series presents an overview of the biochemical properties of five families of peptide growth factors that are thought to be involved in wound healing: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF). PMID- 8506975 TI - Protecting the general surgeon. PMID- 8506976 TI - Local excision of rectal carcinoma. PMID- 8506977 TI - Screening mammography for breast cancer. PMID- 8506978 TI - Serum total IgE levels in a representative sample of a Greek population. I. Correlation with age, sex, and skin reactivity to common aeroallergens. AB - The distribution of IgE in a large randomly stratified Greek population sample was determined in 1187 subjects (793 men and 394 women) aged between 20 and 60 years. Skin prick testing was performed and serum total IgE expressed in iu/ml was measured by Phadebas PRIST: the data are presented as the geometric mean. Subjects were classified as atopic (257 men, 118 women) and nonatopic (536 men, 276 women) according to the results of skin testing with various aeroallergens. At any age, atopic males (120.5 vs 38 iu/ml) and females (99.8 vs 29.3 iu/ml) had higher mean IgE levels, as compared to nonatopic subjects (P < 0.0001). In our adult nonatopic sample, IgE levels did not differ with age (P > 0.05). At any age, nonatopic males had higher (38 iu/ml) mean IgE levels than nonatopic females (29.3 iu/ml) (P < 0.05). The comparison of normal IgE values (nonatopic subjects) from this study with those reported by other investigators revealed that Greek adult males and females had higher IgE levels than populations from other nations. Our results represent the first report on reference values regarding serum total IgE in Greek adults. PMID- 8506979 TI - Skin prick test reactions to brewer's yeast (Saccharomyces cerevisiae) in adult atopic dermatitis patients. AB - The sensitizing capacity of brewer's yeast (Saccharomyces cerevisiae) was studied with the skin prick test method in 449 subjects, including 226 atopic dermatitis (AD) patients, 50 patients with allergic rhinitis (AR) and/or asthma (A), and 173 nonatopic controls. A positive SPT reaction (> or = + +) was seen in 94% of patients with severe AD, in 76% with moderate AD, and in 25% with mild AD or no history of AD. Patients with AR and/or A and nonatopic controls displayed a positive reaction in only 8 and 2% of cases, respectively. There was also a parallel skin prick test reactivity with other yeasts including Pityrosporum ovale and Candida albicans, suggesting cross-reactivity. Parallel skin reactivity was observed also with molds and animal dander but not with pollen or house-dust mite. A significant correlation was also found between total serum IgE level and skin prick test (SPT) results with S. cerevisiae. PMID- 8506980 TI - Enzyme-linked immunosorbent assay for detection of antibodies to the unmodified beta-lactam ring. AB - Dose- and pH- dependent carbodiimide-mediated coupling of Penicillin-G to polystyrene microtiter-plates that leaves the beta-lactam ring unchanged is described. A new ELISA method was developed using Penicillin-G coated plates. The binding of 3 different monoclonal antibodies as well as human IgG antibodies of the IgG1 and IgG3 subclasses is demonstrated, whereas IgG2, IgG4 and IgE antibodies did not bind. Thus, covalently coupled Penicillin-G can be used to study the immune-response to the unchanged beta-lactam ring in patients receiving penicillin therapy. The new method is complementary to hitherto described techniques, which generally only allow detection of antibodies binding to penicilloyl-groups. PMID- 8506981 TI - Mite (Der p 1, Der f 1) and cat (Fel d 1) allergens in the homes of babies with a family history of allergy. AB - Carpet and floor dust samples were collected in four different seasons, from 39 Swedish homes of babies with a family history of allergy. House-dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. Both mite and cat antigens were detected in 94% of the samples and in all homes, but the levels were low (Der p 1, range 15 ng-1944 ng/g fine dust; Der f 1, range 14 ng-264 ng/g of fine dust; Fel d 1, range 16 ng-3120 ng/g fine dust). Mite-allergen levels were significantly higher (P < 0.001) in floor dust than in carpets, and D. pteronyssinus predominated. In contrast, the levels of cat antigen were significantly (P < 0.05) higher in carpets than in floor dust. There was no clear relation between mite-allergen levels and type of house, except that the higher values were found in homes with dampness problems. Cat-allergen levels were higher than total mite-allergen content, and the highest levels were found in homes with a cat (P < 0.05). Rather high concentrations of cat allergen were also found in homes without a cat, which may explain why cat sensitization is so common in Sweden. As the prevalence of house-dust mite sensitivity is increasing in Swedish children, and as the individual patient threshold for eliciting symptoms varies, we suggest that sensitization may possibly occur at a lower exposure level than generally accepted as risk level for sensitization (2 micrograms/g dust). PMID- 8506982 TI - Investigation of basophil cell proteinase release in progressive systemic sclerosis. AB - The aim of this study was to evaluate the function of basophil granulocytes in 37 patients with progressive systemic sclerosis (PSS). The in vitro proteinase release test using Chromozyme TH as a chromogenic substrate was performed to measure the basophil cell releasability. Anti-IgE, calcium-ionophore (A 23187) and N-formyl-methyonil-leucyl-phenylalanine were used as activatory agents. Our results showed that the reactivity pattern to those agents did not differ in PSS compared to controls. Patients whose basophil cells release proteinases to all of the 3 activators tended to have more severe organ symptoms compared to the rest of the patients, while teleangiectasia was significantly less frequently (p < 0.02) found in cases with proteinase release. These findings suggest that there may be a certain relationship between basophil function and severity of the PSS. PMID- 8506983 TI - Common allergenic structures in hazelnut, rye grain, sesame seeds, kiwi, and poppy seeds. AB - Allergy to kiwi, poppy seeds, and/or sesame seeds often occurs in patients with a simultaneous sensitization to nuts and flour. Previously cross reactions have been verified by RAST inhibition. In this study the nature of this cross reactivity is further characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by immunoblotting to nitrocellulose. The degree of cross-reactivity among kiwi, sesame seeds, poppy seeds, hazelnuts, and rye grain was found to be very high in the patients studied. The existence of both cross-reacting and unique components was observed; however, the cross reacting and unique components could be different for different patients. PMID- 8506984 TI - Inhaled methacholine does not influence the cellular composition of bronchoalveolar lavage fluid. AB - A methacholine or a histamine test is often used to quantitate bronchial responsiveness, in studies investigating the influence of various inhaled stimuli on the responsiveness and composition of bronchoalveolar lavage (BAL) fluid. Histamine has been shown to evoke an inflammatory cell response in BAL fluid. In order to test the influence of the methacholine test on the cellular composition of BAL fluid, we investigated 14 healthy, nonsmoking volunteers with a methacholine test 24 h before performing a BAL. The results showed no significant changes in the cellular composition of BAL fluid, as compared with control BAL in the same persons. PMID- 8506985 TI - Effect of lifestyle on levels of specific IgE antibodies. AB - Specific IgE antibodies against cobalt-conjugated human serum albumin (Co-HSA) were determined in serum samples from 706 hard metal workers who responded to a questionnaire on 17 physical and mental health practices. Hard metal (an alloy of cobalt) exposure resulted in significant (P < 0.05) increases in Co-HSA RAST indices in male subjects. In contrast, no factor concerning health practices made an independent contribution to elevation or suppression of specific IgE levels against cobalt. Although total IgE level was found to be significantly (P < 0.01) modulated by the cumulative health practice index (HPIA: Health Practice Index in Allergic reaction), which was extracted by MANOVA analysis while controlling for sex, age, and environmental factors, no significant association was found between HPIA and specific IgE level against cobalt. Multiple logistic analysis also revealed that health practices and hard metal exposure had a significant relative risk (> 2.3; P < 0.05) of elevating Co-HSA RAST index when the total IgE level was more than 400 IU/ml. Thus, a healthy lifestyle as well as discouragement of occupational exposure may be of benefit in reducing allergic disorders for persons with high IgE levels. PMID- 8506986 TI - Heterogeneity of atopy. I. Clinical and immunologic characteristics of patients allergic to cypress pollen. AB - The heterogeneity of pollen-allergic persons is well known but poorly characterized. Cypress is one of the major pollen-producing plants of the Mediterranean area. A study was undertaken to characterize the symptoms presented by patients allergic to cypress pollen and the heterogeneity of the IgE immune response between patients allergic only to cypress pollen and those who are polysensitized. Eighty-nine patients allergic to cypress pollen were studied, 26 being allergic only to cypress pollen. The IgE response was assessed by skin prick tests and the titration of serum total IgE and cypress-specific IgE by RAST. Clinical reactivity was assessed by symptom scores during the cypress pollen season and skin tests. Pollen counts were obtained. The clinical reactivity was similar in both patient groups. Rhinitis was present in all patients, conjunctivitis in 73.7-88.5%, and asthma in only 7.4-19.2%. The age of onset of symptoms caused by cypress pollen allergy was significantly greater in patients allergic to cypress pollen only. Total serum IgE was within the normal range in the cypress pollen group and significantly lower than in the polysensitized groups. Cypress pollen RAST was higher in the polysensitized group. We concluded that conjunctivitis is particularly common in cypress pollen allergy. Patients allergic only to cypress pollen may be unique in their way of expressing serum total IgE levels. PMID- 8506987 TI - Interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-2, and arachidonic acid metabolites modulate IL-4-induced IgE synthesis similarly in healthy persons and in atopic dermatitis patients. AB - The role of cytokines and arachidonic acid metabolites in the regulation of IgE production in healthy persons and in atopic dermatitis patients with elevated IgE levels was studied. Interleukin-4 (IL-4) induced IgE production in peripheral blood mononuclear cells (PBMCs) of all donors, and no significant difference was found between the amounts of IgE produced by healthy persons and atopic dermatitis patients. Similarly, recombinant interferon (IFN)-alpha and IFN-gamma, as well as IL-2, inhibited IL-4-induced IgE production to a similar extent in both study groups. To evaluate the role of arachidonic acid (AA) metabolites in the regulation of IgE production, we added indomethacin, an inhibitor of the cyclooxygenase pathway, or nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway, to IL-4-treated cultures. Both indomethacin and NDGA strongly inhibited IL-4-induced IgE production. They also inhibited IL-4-induced IgG4 synthesis. No significant difference in the amount of inhibition was found between the two study groups. We were unable to restore the NDGA-induced inhibition of IgE-production by adding leukotrienes B4, C4, D4, or 5-HETE to the NDGA-treated cultures. PGE2 also failed to restore the indomethacin-mediated inhibitory effect. Consequently, NDGA- and indomethacin-mediated inhibitory effects do not appear to be mediated by any single factor studied. Collectively, our results show IFNs and IL-2 to be similar in effect in the modulation of IL-4 induced IgE synthesis in healthy and atopic persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8506988 TI - Comparison of the effects on bronchial hyperresponsiveness of antiallergic agents and beclomethasone dipropionate in long-term bronchial asthma. A retrospective study. AB - The effect of antiallergic agents (DSCG) (disodium cromoglycate, ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic-agents-treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI-treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC20 was from 310 to 597 micrograms/ml (P < 0.01) in group A, from 308 to 1622 micrograms/ml (P < 0.0005) in group B, and from 575 to 525 micrograms/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom-free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC20 by BDI treatment (mean PC20: 311-->1828 micrograms/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long-standing bronchial asthma. PMID- 8506990 TI - Elimination of viral infection risk from blood samples for allergy testing. PMID- 8506989 TI - Is the allergen-inhalation challenge predictive of the severity of seasonal asthmatic exacerbations? AB - Fifteen asthmatic patients sensitized to Parietaria pollen were studied. Before the pollen season they underwent an allergen-inhalation challenge which was preceded and followed by a methacholine-inhalation challenge. Pollen count, symptom score, and drug consumption were monitored daily throughout the study. A severity score was obtained by adding symptom score and drug consumption. Patients underwent a third methacholine challenge during the pollen season, after they had been exposed to a high atmospheric concentration of pollen. The severity score during the first period of the pollen season was significantly correlated with both the early and the late asthmatic responses to the allergen observed before the season (r2 = 0.50; P < 0.005). Bronchial sensitivity to methacholine was significantly increased both after allergen challenge and after seasonal exposure, but these increases correlated neither with each other nor with the severity score. We conclude that bronchial responses to experimental exposure to allergens, but not the changes in nonspecific airway responsiveness, can, in part, predict the severity of asthma exacerbation during the pollen season. PMID- 8506991 TI - Occurrence of IgE antibodies against the 39-kDa allergen component of the mite Lepidoglyphus destructor in urban and rural subjects. AB - Several species of storage mite have been shown to cause IgE-mediated sensitization. Monoclonal antibodies (mabs) have been raised against the storage mite Lepidoglyphus destructor, and one mab (42B6) immunoprecipitated a band of 39 kDa of L. destructor. To search for the frequency of IgE antibodies in patient sera against this allergen component, we modified a radioimmunoassay (RIA), 42B6 being used as capturing antibody. Twenty of 43 sera from farmers who were RAST positive to L. destructor (46.5%) were scored as positive in this assay. There was a moderate degree of correlation between positive RAST results to L. destructor and the 39-kDa allergen. Among 14 sera from Stockholm residents positive in RAST to both Dermatophagoides pteronyssinus and L. destructor, six detected the 39-kDa allergen component. However, three sera from urban subjects lacking IgE antibodies against both mite species also had IgE antibodies against the 39-kDa allergen. The present study demonstrates that the 39-kDa allergen of L. destructor is an important allergen, and that rural as well as urban subjects can become sensitized. PMID- 8506992 TI - Respiratory allergy and atopic eczema in a thatcher due to storage and house dust mite allergy. PMID- 8506993 TI - Anaphylaxis caused by banana. AB - An anaphylactic reaction following ingestion of banana occurred in a 32-year-old female cook. The sensitization to banana occurred simultaneously with the development of occupational asthma caused by grain flour. The patient was sensitized to a wide range of airborne and ingestible proteins but not to rubber latex. PMID- 8506994 TI - Pulmonary neuroendocrine cells in species at high altitude. AB - Ever since pulmonary neuroendocrine cells were first described, a chemoreceptor function has been attributed to them. This hypothesis proposes that the innervated clusters of these cells, which are known to degranulate when the oxygen tension around them is reduced, respond to hypoxia to initiate activity in a reflex arc and ultimately adjust some aspect of pulmonary function. If this were true, one might expect to see changes in the pulmonary neuroendocrine system in species exposed to the unremitting hypoxia at natural high altitude. Whilst evidence from some studies suggests that such changes do occur, others have been unable to demonstrate any effect. To some extent this may be attributable to species variability, but might also reflect whether the organism is genetically adapted or merely acclimatized to life in an oxygen-poor environment. PMID- 8506995 TI - Patterns of proliferation and differentiation during fetal development of the airway epithelium. PMID- 8506996 TI - Pulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia. AB - Despite four decades of investigation, the function of pulmonary neuroendocrine cells (NEC) remains unclear. Since NEC secretory products may influence airway growth or differentiation or alter airway smooth muscle tone, increased numbers of NEC seen in bronchopulmonary dysplasia (BPD) may be partially responsible for the genesis of the structural and pathophysiological alterations seen in this disease state. Changes in airway structure were studied in six infants dying with BPD and six conceptional age-matched control infants dying of noncardiopulmonary disease. Changes in bombesin-, calcitonin-, and serotonin-immunoreactive NEC were quantified in lung specimens from three infants who died at 2 months of age with severe BPD and three conceptional age-matched controls. There were no differences in either bronchiolar or bronchial airway epithelial areas, but significant increases in bronchiolar (1.8-fold) (P < 0.001) and especially bronchial smooth muscle (2.5-fold) (P < 0.001) were documented in infants with BPD. Few bombesin-, calcitonin-, and serotonin-immunoreactive cells were identified in cartilaginous airways; however, there was a clear increase in the total number of bronchiolar immunoreactive cells in infants with severe BPD (28.5 +/- 11.2 cells/mm airway epithelium) compared to control infants (4.5 +/- 4.9) (P < 0.05). Our results confirm that airway wall composition does change in BPD, but there is either no or an inverse correlation between NEC number and airway epithelial and smooth muscle areas and cell numbers. The role of NEC secretory products in airway smooth muscle growth and function requires further investigation. PMID- 8506997 TI - Pulmonary neuroendocrine cells in tobacco-related lung disorders. PMID- 8506998 TI - Cholinergic-nicotinic control of growth and secretion of cultured pulmonary neuroendocrine cells. AB - Dispersed newborn hamster lung cells were established in vitro in a defined, low serum growth medium. Neuroendocrine markers (immunohistochemistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. While the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 weeks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [3H]thymidine incorporation were significantly increased. The stimulatory effect of chronic nicotine was reversed by the coadministration of the nicotinic antagonist hexamethonium. In another set of experiments, prior multiple transplacental nicotine pretreatments resulted in a significant increase in iCT in the lungs of newborns; when these lungs were subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that observed in the control culture. In contrast, in vivo, the lung iCT remained significantly elevated at 1 week post-parturition. Cell culture supernatants were analyzed at week 4 for the evoked release of iCT; cholinergic-nicotinic agonists promptly increased the supernatant iCT, which was blocked by nicotinic but not by muscarinic antagonists. We suggest that this in vitro system provides a useful tool to study directly the PNE cell. The acute and chronic effects of nicotine are most likely related to stimulation of cholinergic nicotinic receptors on iCT-containing PNE cells. PMID- 8506999 TI - Hypercalcitonemia in inhalation burn injury: a response of the pulmonary neuroendocrine cell? PMID- 8507000 TI - Transgenic technologies. PMID- 8507001 TI - Neuroepithelial bodies and growth of the airway epithelium in developing hamster lung. AB - Clusters of small-granule endocrine cells, neuroepithelial bodies (NEBs), appear in the airway lining of pseudoglandular lungs, but their prenatal function has remained obscure. Transplacental labeling of S-phase cells in Syrian golden hamsters has allowed us to relate NEBs to patterns of replication in the surrounding endoderm. Two methods were used: 1) continuous exposure to 3H thymidine for the last 25% (4 days) of gestation, and 2) 2-hr exposure to 5-bromo 2'-deoxyuridine (BrdU) on fetal day 15. 3H-thymidine incorporation was assessed in autoradiographs of neonatal lung by grain counting from 923 nonendocrine and 251 endocrine cells in 28 airway epithelial terrains, each centered on a NEB: 12 in the perihilar, 8 in the middle, and 8 in the distal third of the left axial bronchus. Grain densities for 10-25 nonendocrine cells on either side of the NEB were plotted vs. position relative to the endocrine cell cluster and analyzed by rank-order correlation and linear regression. Label was highest in cells closest to NEBs in all 12 terrains (P < 0.05-0.001) in the perihilar airway, in 3 of 8 terrains (P < 0.025-0.001) in the middle third of the bronchus, and in respective, pooled populations (P < 0.001). The effect was not demonstrable in the distal third of the airway. In the 15-day fetus 243 mm of airway perimeter were measured and 3,218 BrdU-labeled epithelial cells counted from sections through the entire length of the left axial airway and the lobar bronchus, intermediate, and terminal bronchioles of the infracardiac (IC) lobe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507002 TI - Role of airway smooth muscle in asthma: possible relation to the neuroendocrine system. AB - Though not yet firmly established, it appears likely that the neuroendocrine system (NES) regulates airway smooth muscle function. As it is the latter which is altered in asthma, the importance of the role of the NES in this disease is clear. The fact that transmitters from the NE cells are released from their basal aspect, and are in close proximity to the subjacent airway smooth muscle, further indicates an interaction. The question then arises as to what are the experimental desiderata for conducting studies of the ASM. These should constitute what Sergei Sorokin has called the "Koch's postulates of airway smooth muscle research." As human tissues from asthmatics are difficult to obtain, animal models have been developed. The requirements are that, in these animals, the allergy be IgE based, that a congenital or familial factor be operative, that a noncholinergic nonadrenergic inhibitory system be a component of the neural regulatory system, and that the antigen for immunization be of a type commonly found in human asthmatics. Ideally, evidence of clinical asthma and exercise induced asthma and nocturnal attacks should also be present. Unfortunately, no ideal animal models exist and one cannot talk about asthmatic animals, but only of animals with allergic bronchospasm. If in vitro research is to be conducted, there are additional requirements. The tissue should be from a relevant location. The tracheal smooth muscle which has been the favorite, purely because of its convenience, is not a good model. For the early asthmatic attack, central bronchi (3-5 mm diameter) should be used. Muscle strips obtained from them should be parallel-fibred and the cartilage plaques should be carefully dissected away, otherwise they contribute unwanted frictional forces when velocity is measured. Care should be taken to ensure that the epithelial cell layer is intact, as evidence indicates that it may regulate airway muscle function, though this has not been established for all the animal species used in asthma research. The isolated muscle strip should be in a steady state, particularly with respect to the functional variable under study, before definitive data are collected. Most importantly, it is shortening capacity that must be studied, as this is the in vitro analogue to in vivo narrowing of airways. Isometric force development provides information about wall stiffness and is of very little relevance to the elucidation of the mechanism of bronchospasm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8507003 TI - Lung endocrine cell markers, peptides, and amines. PMID- 8507004 TI - Neuroendocrine cell populations in postnatal human lungs: minimal variation from childhood to old age. AB - Although changes in the human pulmonary neuroendocrine system have been described in association with a variety of pulmonary diseases, little is known of how the system changes with age in healthy lungs. As delineated by their immunoreactivity for neuron-specific enolase, protein gene product 9.5 and chromogranin A, the density of the system's component cells in terms of the rest of the pulmonary epithelium varied minimally between 10 groups of subjects divided according to age and ranging from children to nonagenarians, figures for the groups varying only between 2.91 and 4.19 neuroendocrine cells per 10,000 epithelial cells. In only three subjects were neuroendocrine cells found in the parenchyma; the vast majority were located in airways with about 65% in bronchi. Cells were more often arranged in the form of clusters in the younger subjects than in the elderly, in whom clusters were extremely rare, but the significance of this observation is unclear. PMID- 8507005 TI - Ultrastructure and innervation of neuroepithelial bodies in the lungs of newborn cats. AB - Neuroepithelial bodies (NEB) occur throughout the airway mucosa and alveolar parenchyma of kitten lungs. In the bronchi, they are often situated on top of a cartilage plate. They form compact corpuscles containing 10-20 corpuscular cells and appear covered with a layer of flattened Clara cells. Kitten NEB are occasionally observed to display mitosis of the corpuscular epithelial cells. A prominent blood capillary lies at their basal pole. The corpuscular cells contain numerous dense core vesicles (DCV), whose number and diameter remain unchanged with age. Kitten NEB are innervated by nerve fibres that "loop" through the corpuscle and form morphologically afferent as well as efferent nerve endings. The nerve endings display afferent synaptic junctions with the corpuscular cells and sometimes run in clusters, so that they contact each other. Many nerve endings undergo spontaneous degeneration. We conclude that kitten NEB are well adapted to function as chemoreceptors and as endocrine or paracrine organs. Their chemoreceptor activity could be modulated by axon reflexes since their afferent nerve endings are often continuous with the efferent ones, as well as by interneural modulation since nerve endings often form clusters. In addition, kitten NEB innervation appears to involute rapidly soon after birth. This may indicate that their chemoreceptor function is only of primary importance during gestation and at birth. However, the secretory function of kitten NEB, as evidenced by the unchanged numbers and dimensions of their DCV, seems to remain steady throughout life. PMID- 8507006 TI - Immunocytochemical expression of protein gene product (PGP) 9.5 in the cat bronchopulmonary neuroendocrine cells and nerves. AB - Variously fixed, wax-embedded lung and gastrointestinal serial tissue sections from newborn to adult cats were stained with hematoxylin-eosin (H&E), Grimelius' silver, and immunohistochemical techniques using antisera to protein gene product (PGP) 9.5, a neuron-specific protein under strong evolutionary constraints. PGP 9.5 is revealed as a pan-neuroendocrine marker useful for tracing the pulmonary diffuse neuroendocrine system (PDNES) and studying the relationships between neuronal and neuroendocrine elements at various stages of life. Its occurrence is also compared in the pulmonary and the gastrointestinal tract. In spite of a close resemblance to already described neuroepithelial bodies (NEB) of other mammals, cat NEB feature typical constitutional and distributional difference, illustrating interspecies differences. The number of PGP 9.5 immunopositive pulmonary neuroendocrine cells declines gradually after 3 weeks and throughout adult life. Immunoreactivity in neuronal elements is lost after 1 week of age. In gastrointestinal tissues, only neuronal elements immunostain, suggesting functional variations or a separate embryological origin for enteroendocrine cells. PMID- 8507007 TI - Localization of cholecystokinin-like peptide in neuroendocrine cells of mammalian lungs: a light and electron microscopic immunohistochemical study. AB - We report immunohistochemical localization of cholecystokinin (CCK)-like immunoreactivity at the light and electron microscopy (EM) level in pulmonary neuroendocrine (NE) cells of human and other mammals (monkey, rabbit, rat, hamster, pig, dog and lamb). In addition, immunolocalization of CCK-like peptide was compared with that of bombesin (predominant peptide in human lung) and serotonin (an amine found in NE cells of most species). While CCK-like and serotonin-like immunoreactivity were identified in both solitary NE cells and NE cell clusters (neuroepithelial bodies, NEB) of all species studied, bombesin-like immunoreactive NE cells were found in human and monkey lungs only. The distribution and intensity of immunostaining for CCK-like peptide varied between species with some showing relatively high levels of expression (e.g., monkey, piglet, dog and lamb), others intermediate (human, rabbit) or weak immunostaining (rat, hamster). At the EM level, CCK-like immunoreactivity was localized in dense core vesicles (DCV), the expected site of peptide storage. Using a double immunolabeling technique, CCK and serotonin were colocalized in some, but not all DCV. The potential role of CCK in the lung (or for other pulmonary peptides) may include a variety of functions such as modulation of bronchial or vascular tone, growth factor-like and/or hormonal effects. PMID- 8507008 TI - Colocalization of peptide hormones in neuroendocrine cells of human fetal and newborn lungs: an electron microscopic study. AB - This study investigated the colocalization of the peptide hormones bombesin or calcitonin with calcitonin gene related peptide (CGRP) in neuroendocrine cells (NE) in the lungs of human fetuses of varying gestational ages and in the lungs of newborn infants who died with acute or chronic lung disease in the first weeks or months after birth. Double immunolabeling of dense core granules for these peptides was also studied in this same patient population. On-grid double gold immunolabeling was carried out on 29 subjects using anti-bombesin and anti-CGRP and on 22 subjects using anti-calcitonin and anti-CGRP as primary antibodies, the secondary antibodies being labeled with different-size gold spheres. Colocalization of both bombesin and calcitonin with CGRP was demonstrated, not only in the same NE cell, but also on the same dense core granule. Colocalization was rarely found in normal fetuses, and most frequently found in newborn infants with acute lung disease, usually hyaline membrane disease (HMD), or with the development of chronic lung disease in the first weeks or months after birth. Double labeling of the same dense core granules might imply action of peptides in concert, or perhaps one peptide acting in a paracrine role (e.g., on bronchial or bronchiolar smooth muscle) and the second peptide acting in an autocrine fashion on the parent cell (e.g., in the regulation of granule production or release). PMID- 8507009 TI - Development of PGP 9.5- and calcitonin gene-related peptide-like immunoreactivity in organ cultured fetal rat lungs. AB - Knowing that small-granule endocrine cells develop in organ cultured fetal lungs, we investigated whether the cells produce regulatory peptides in vitro, and if sufficient amounts appear to permit using the cultures as an experimental system for physiological study of secretory mechanisms. The paired lungs from 14-day and 15-day fetal rats were organ cultured for 1-8 days and examined daily for development of immunoreactivity against marker proteins and regulatory peptides associated with small-granule endocrine cells and nerves. They proved reactive against protein gene product 9.5 (PGP) and calcitonin-gene related peptide (CGRP) but not against calcitonin or neurofilament protein 200 K, although positive controls were obtained for these substances in lungs from postnatal animals. Initially PGP-like immunoreactivity is associated with cell bodies and processes of neuroblasts which run medial to the bronchial axis on day 14 and are increasingly prevalent on day 15. In 15-day explants PGP becomes detectable after a day in vitro in rare "clear cell" precursors of small-granule cells located in the epithelium lining proximate parts of the lungs, although in 14-day explants comparable reactivity is not seen until the third day (14 + 3 days). In culture PGP-positive neuroblasts increase in number, and nerve processes gradually extend down the airway to encircle the sleeve of smooth muscle that develops as the bronchial tree expands. Concurrently, the initially small clusters of small granule cells increase in size, and new ones appear in the airway lining. By 15 + 5 days they extend to the boundary between a taller, more proximal epithelium and a glycogen-rich cuboidal layer that lines one or two most-distal generations of branches. Thereafter, the trachea and central, cartilage-bound segments of the primary bronchi mainly contain solitary endocrine cells and the more peripheral lung a mixture of single cells and clusters, much as in near-term lungs in vivo. At this stage PGP-positive nerves extend as far as the entrances of the terminal sacs, and most are distributed to the airway muscle plexus. Exceptionally, they may innervate a small-granule cell cluster, converting it into a neuroepithelial body. CGRP-like immunoreactivity initially appears in small-granule cells of 15 + 2-day cultures but does not develop in ganglion cells or nerves. It localizes to endocrine cells at all conducting airway levels, increasing in staining intensity and accounting for most if not all of the PGP-positive population between 15 + 4 15 + 8 days.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8507010 TI - Calcium and ionophore A23187 lower calcitonin gene-related peptide-like immunoreactivity in endocrine cells of organ cultured fetal rat lungs. AB - Small-granule endocrine cells differentiate in airway epithelium of intact and cultured fetal rat lungs. We noted that the cells store calcitonin gene-related peptide (CGRP) in vitro as well as in vivo and used the ionophore A23187 to test the effects of calcium on peptide secretion in this system. Lungs of 14-day and 15-day fetal rats, organ cultured for 6-9 days, were divided into groups of 5 explants each and incubated for 15 min at 37 degrees C in the basic medium containing 0 mM, 1 mM, or 10 mM CaCl2, with or without 8 microM A23187, or 10 mM EGTA. Intracellular CGRP in these explants was quantified by supraoptimal dilution peroxidase immunocytochemistry (Springall et al.: J. Pathol. 155:259 267, 1988): counts were made of endocrine cells stained with a 1/60,000 dilution of anti-CGRP and repeated on the same sections after restaining with antibody diluted at 1/1,000. Results, analyzed by Chi-square test, were expressed as % cells stained with antibody at 1/60,000 vs. those stained at 1/1,000. Immunoreactivity for CGRP was significantly reduced by A23187 in the presence of high extracellular Ca2+ (10 mM), the inference being that these cells secrete peptide hormones in response to Ca2+ influx across the plasma membrane. The organ cultures evidently can be used to assess certain physiological responses of lung endocrine cells in an accessible, relatively organotypical setting. PMID- 8507011 TI - Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs. AB - Human pulmonary neuroendocrine cells produce a variety of hormones, including mammalian bombesin (BN) or gastrin-releasing peptide (GRP). Neuroendocrine cell hyperplasia and increased release of BN-like peptides occur in several diseases of the airways, including chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia. Growth stimulation of human bronchial epithelial cells by BN, as measured in a colony-forming assay, has been reported previously (Willey et al.:Exp. Cell Res. 153:245-248, 1984). In a follow-up to this report, we examined the response of human bronchial epithelial (HBE) cells to BN or GRP in a similar system, using cells derived from 13 human tissue donors. A stimulatory response (increased colony-forming efficiency) was found in cultures from 8 donors, including 3 with COPD. Statistical significance was found for the data from 5 of these 8 donors. The other 5 donors, 1 normal and 4 lung cancer patients, showed inhibition of colony formation by BN or GRP. Statistical significance was found for 3 of these donors. The ability of BN analogs to modulate BN stimulation was examined in cells from a donor with COPD. [psi Leu13,Leu14] BN(1-14), a BN antagonist, blocked the stimulation induced by BN. [D Cpa6,psi Leu13,Phe14] BN(6-14), a mixed agonist-antagonist, showed partial agonist activity in HBE cells. [D-Phe1,Leu8,9] Litorin, an agonist, also showed agonist activity in a colony-forming assay with cells from these donors. These results indicate that responsiveness to BN/GRP may vary widely in the human population. Responsiveness may be heightened in disease states involving a proliferation of neuroendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507012 TI - Chronic hyperoxia and hamster pulmonary neuroendocrine cell bombesin and calcitonin. AB - Hamsters were exposed to 60% hyperoxia for 1 week, 3 weeks, or 3 months. The exposed animals gradually failed to gain body weight as controls. The pulmonary neuroendocrine (PNE) cell peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT), were determined in the lung and the serum. At 1 week and 3 weeks, lung MB was unchanged while the iCT levels were markedly depleted. In contrast, the lung levels of both MB and iCT were significantly elevated at 3 months. Serum levels of MB showed an initial decline at 1 week, which was followed by augmented levels at 3 weeks and at 3 months. In contrast, serum iCT showed considerable depletion at 1 week, and also at 3 weeks, followed by increased levels at 3 months. Thus, chronic exposure to hyperoxia causes profound perturbation of PNE cell peptides. In particular, the early depletion of lung and serum iCT appears to be a unique feature of the response to hyperoxia. The principal difference between the MB and the iCT responses was the lack of an initial depletion of lung MB, and the earlier rise of serum MB to supranormal levels. It seems likely that the early peptide effects of hyperoxia are related to oxygen toxicity upon the PNE cells, while the changes noted at 3 months reflect a hyperplastic accommodation of PNE cells to the prolonged oxygen exposure with resultant increases in MB and iCT. This response is distinctly different from that we have seen previously in hamsters exposed to hyperoxia combined with a nitrosamine, or a nitrosamine alone. PMID- 8507013 TI - Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures. AB - Fetal pulmonary neuroendocrine cells (PNECs) contain abundant gastrin-releasing peptide (GRP, mammalian bombesin-like peptide [BLP]). Previously, addition of bombesin resulted in increased fetal lung growth and maturation in utero and in organ cultures. A monoclonal antibody (mAb) to bombesin (2A11) blocked baseline automaturation of lung organ cultures in serum-free medium. In the present study, we analyze lung development following daily in utero administration of 2A11 from gestational days 15-18. Fetal lung treated with 2A11 and then harvested on day 18 demonstrated a dose-dependent decrease in surfactant phospholipid synthesis compared to controls treated with MOPC, an unreactive mAb. However, 2A11-treated fetal lung harvested on day 17 showed paradoxical increases in 3H-choline incorporation into saturated phosphatidylcholine, 3H-thymidine incorporation into DNA, and relative numbers of differentiated type II pneumocytes. In serum containing day 17 lung organ cultures, 2A11 stimulated choline and thymidine incorporation. Since epidermal growth factor (EGF) is the only agent besides bombesin known to stimulate both fetal lung growth and maturation, we added EGF to serum-free cultures and reconstituted the stimulatory effects. A murine EGF receptor mAb (ERA) blocked 2A11-induced lung growth and maturation in serum containing cultures, and this effect was overcome by adding EGF. In vivo, ERA also blocked stimulatory effects of 2A11 in fetal lung on day 17. These observations suggest that EGF receptor up-regulation may maintain lung growth and maturation if BLP levels are diminished on day 17. Nonetheless, BLPs appear to be involved in lung maturation on day 18, supporting a role for PNECs in normal lung development. PMID- 8507014 TI - Heterogeneity studies of hamster calcitonin following acute exposure to cigarette smoke: evidence for monomeric secretion. AB - Various acute stimuli, including cigarette smoke, induce hypercalcitonemia in man and hamsters. We have shown that this occurs also in thyroidectomized subjects. In the present study we have further explored this phenomenon of secretion from the lungs by studying, simultaneously, the HPLC characteristics of pulmonary tissue and serum in control hamsters and in animals immediately following short term exposure to cigarette smoke. In addition, we have studied the immunoheterogeneity of lung calcitonin 24 hours following the acute exposure. Control lungs contained monomeric immunoreactive calcitonin (M-iCT), high molecular mass iCT (H-iCT), and CT fragments. Immediately following smoke exposure, there was an acute decrease of lung iCT by radioimmunoassay (RIA) which consisted primarily of a decrease in M-iCT by HPLC. Simultaneously, the iCT increase in the serum by RIA was shown by HPLC to involve M-iCT. Twenty-four hours after smoke inhalation, the lung iCT by RIA and M-iCT by HPLC had returned towards control levels. These findings document the molecular characteristics of lung iCT following acute cigarette smoke stimulation, and suggest that under certain circumstances M-iCT may be actively secreted by the lung. It remains to be determined whether this type of secretion reflects hemocrine or paracrine release and what the physiological role for such a secretion may be. PMID- 8507015 TI - Cell biology of pulmonary neuroepithelial bodies--validation of an in vitro model. I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense core vesicles. AB - Pulmonary neuroendocrine (NE) cells including the innervated clusters of NE cells -neuroepithelial bodies (NEB)--are difficult to study because of their small numbers and diffuse distribution within the airway mucosa of the lung. We have previously reported a method for isolation and culture of NE cells from rabbit fetal using a combination of mechanical and enzymatic dissociation followed by gradient centrifugation. This method provides single cell suspension of mixed lung cells enriched in NE cells, particularly those originating from NEB. This study further validates our in vitro model by detailed morphologic characterization of cultured NEB cells using high resolution light microscopy, transmission and scanning electron microscopy, HPLC for detection of serotonin (5 HT), and molecular (Northern blot) analysis of mRNA encoding for 5-HT synthesizing enzymes, tryptophane hydroxylase, and aromatic L-amino acid decarboxylase. In addition the effects of hypoxia on NEB cells in vitro were investigated to define the role of these cells as possible airway chemoreceptors. Exposure of NEB cultures to hypoxia resulted in decreased intracellular content of 5-HT accompanied by increased exocytosis of dense core vesicles (DCV). The amount of 5-HT release correlated with the degree of hypoxia, suggesting modulation by ambient pO2 levels. The role of Ca2+ ions in exocytosis of DCV and 5-HT release from NEB cells was tested in experiments with Ca2+ ionophore (A23187). Exposure of cultures to 5 micrograms/ml of ionophore resulted in up to 40% reduction in 5-HT content of NEB cultures as well as increased exocytosis of DCV. Our overall findings are consistent with a view that NEB cells are chemosensory in nature and that Ca2+ signaling pathway is involved in stimulus secretion coupling. Further refinements in cell separation and culture methodology are required before more detailed investigation of NEB cell membrane properties, signal transduction mechanisms, and intracellular signaling pathways can be carried out. PMID- 8507016 TI - Calcitonin gene-related peptide and pulmonary hypertension in experimental hypoxia. PMID- 8507017 TI - The future of dental education. PMID- 8507018 TI - Comparison of nalbuphine and fentanyl as intravenous analgesics for medically compromised patients undergoing oral surgery. AB - This study compared the efficacy and side effects of equianalgesic doses of nalbuphine and fentanyl as intravenous (IV) analgesics for medically compromised patients undergoing oral surgery with local anesthesia. A total of 24 inpatients scheduled for oral surgery and with an ASA physical status of 3 or 4 were randomly assigned to two treatment groups and received IV analgesia with an injection of either 0.2 mg/kg nalbuphine or 2 micrograms/kg fentanyl. Three minutes later, local anesthesia was administered. Respiratory rate, heart rate, arterial blood pressure, and oxyhemoglobin saturation (SpO2) were recorded before and during surgery. After the operation, the patient, surgeon, and anesthesiologist were asked to complete questionnaires regarding drug effects. Analgesia and sedation appeared sufficient and comparable according to the surgeon, anesthesiologists, and patients in the two groups, and there were no significant differences in blood pressure or heart rate. Respiratory rate and SpO2 were lower in patients treated with fentanyl (P < 0.05), and eight patients of this group experienced episodes of oxygen desaturation (SpO2 < 90%) compared with only two patients who received nalbuphine (P < 0.05). Nalbuphine produced less respiratory depression and should be considered a suitable alternative to fentanyl for use in medically compromised patients undergoing oral surgery. PMID- 8507019 TI - Passive dosimetry of dental hygienists' exposure to nitrous oxide. AB - This study is the first to measure exposure to waste nitrous oxide (N2O) in the dental work setting in a broad geographical region (25 states), with passive dosimeters, and for dental hygienists. Thirty-five dental hygienists who reported that they administered N2O and 20 dental hygienists who reported that they never administered N2O constituted the sample. The former (n = 35) received both a 40 hr dosimeter, which measured exposure during administration of N2O, and a 168-hr dosimeter, which measured exposure during all work hours. The latter (n = 20) received only the 168-hr dosimeter. Exposure was measured during 2 wk in April 1990. For all work hours, the mean ppm-hr was 3,636 and the mean time-weighted average (TWA) was 78 ppm. The corresponding means during administration were 2,754 ppm-hr and 842 ppm TWA. The data for dental hygienists with passive dosimeters were similar to previously reported findings for dentists as measured by infrared spectrophotometry and gas chromatography. Hygienists who worked in dental settings with scavenging equipment received higher average levels of exposure to N2O than did hygienists who worked in settings without scavenging. PMID- 8507020 TI - Supplemental oxygen after outpatient oral and maxillofacial surgery. AB - Arterial oxygen saturation (SpO2) was monitored postoperatively with pulse oximetry in 72 dental patients. Intravenous general anesthesia was employed in 57 patients. All of these patients received supplemental oxygen intraoperatively, and of these, 29 received supplemental oxygen postoperatively. Fifteen patients received only local anesthesia without supplemental oxygen and served as the control group. Continuous pulse oximetry revealed 43 episodes of arterial oxygen desaturation (SpO2 decreases greater than 3% from baseline) in patients who did not receive postanesthesia supplemental oxygen and eight episodes of desaturation in patients who did receive postanesthesia oxygen. Patients with a smoking history had more episodes of desaturation than did nonsmokers in the group that received general anesthesia and breathed room air postoperatively. The total amount of methohexital administered had no significant effect on the number of patients with desaturation episodes. These observations emphasize the need for postoperative oxygen for patients who undergo general anesthesia for outpatient oral and maxillofacial surgery. PMID- 8507021 TI - Giant negative T waves after maxillofacial surgery. AB - A patient developed strongly negative T waves following anesthesia for maxillofacial surgery. The electrocardiogram was normal preoperatively, except for a single premature ventricular depolarization, and no abnormalities were noted during the operation. Postoperatively, the T wave gradually inverted in almost all leads and approached the criterion of -10 mm for giant negative T waves in V3 2 days postoperatively. The T wave returned to normal approximately 4 months later. Although the T-wave inversion in this patient may have been caused by surgical trauma to the sympathetic nerve supply to the heart or by myocardial infarction, the exact cause remains undetermined. PMID- 8507022 TI - Propofol and midazolam for conscious sedation in a mentally retarded dental patient. AB - Conscious sedation was provided for a 21-yr-old mentally retarded and cardiovascularly compromised women who required dental extractions, by initially infusing propofol (3 mg/kg/hr), augmented with a bolus dose of intravenous midazolam (1 mg). After 45 min the propofol infusion rate was reduced to 1 mg/kg/hr. The patient remained well-sedated during the entire procedure and no adverse effects were experienced. PMID- 8507023 TI - Subcutaneous emphysema: a complication of surgery and anesthesia. AB - Subcutaneous emphysema is an iatrogenic complication by which air is introduced into the tissues either during or immediately after surgery. A case is presented that demonstrates the complication, following the removal of third molars, believed to be due to violation of the maxillary sinus, an underinflated cuff of a nasotracheal tube, and coughing on extubation. PMID- 8507024 TI - Hypoalgesic effect of EMLA and lidocaine gel applied on human oral mucosa: quantitative evaluation by sensory and pain thresholds to argon laser stimulation. AB - Sensory and pain thresholds to argon laser stimulation were used to evaluate the analgesic efficacy and duration of a eutectic mixture of local anesthetics (EMLA) and a 2% lidocaine gel applied topically on the oral mucosa. Application of EMLA for 2 min on the tongue and gingiva increased the pain thresholds by 92.8% and 63.4% respectively. Corresponding values for lidocaine gel were 53.6% and 21.9%. Standardized variation of the EMLA application period (2, 5, and 15 min) produced significantly different analgesic profiles on the tongue but not on the gingiva. Application of EMLA for 5 and 15 min on the tongue and for 2, 5, and 15 min on the gingiva increased the pain thresholds to a predefined analgesic level (2.15 W) for 2 to 25 min. The present experimental model for assessment of oral mucosa pain is suggested to be well-suited for investigations of intraoral analgesia. PMID- 8507025 TI - Metabolic responses to oral surgery under local anesthesia and sedation with intravenous midazolam: the effects of two different local anesthetics. AB - The effects of epinephrine-free and epinephrine-containing local anesthetic solutions on plasma potassium and blood glucose concentrations were investigated in 20 patients undergoing oral surgery with intravenous midazolam sedation. Ten patients were randomly assigned to receive 4.4 mL of 2% lidocaine with 1:80,000 epinephrine as a local anesthetic and 10 were given 4.4 mL of 3% prilocaine with 0.03 IU/mL felypressin. There were significant changes from baseline potassium and glucose concentrations both within and between treatments in the early postinjection period. The epinephrine-containing local anesthetic significantly reduced the plasma potassium concentration 10 min after injection, by 0.16 +/- 0.20 mmol/L (mean +/- SD), and increased the blood glucose concentration at 10, 20, and 30 min (by 0.46 +/- 0.37, 0.63 +/- 0.45, and 0.56 +/- 0.28 mmol/L, respectively). Conversely, plasma potassium increased and blood glucose decreased 10, 20, and 30 min following the administration of the epinephrine-free solution. At 30 min potassium was increased by 0.24 +/- 0.16 mmol/L, and glucose was decreased by 0.23 +/- 0.16 mmol/L. It is concluded that epinephrine-free and epinephrine-containing local anesthetics differ in their metabolic effects during oral surgery with midazolam sedation. PMID- 8507026 TI - Activating a 2 x 4 appliance. AB - When the long span of wire in a 2 x 4 orthodontic appliance enters a bracket in a nonparallel manner, it develops a couple and tendency for rotation called a moment. The moment of a couple creates inherent equal and opposite Newtonian equilibrium forces not readily sensed clinically. Moments at successive brackets, producing rotations in opposite directions, create equilibrium forces also in opposite directions which are subtractive from each other. When these equilibrium forces are equal and opposite, they cancel each other out. If the moments produce rotations in the same direction, the equilibrium forces are also in the same direction and are additive. The apparent simplicity of the 2 x 4 appliance conceals the fact that it is a powerful orthodontic tool that uses engineering mechanics in a way not possible with fully bracketed appliances. Clearly the application of engineering mechanics is a distinguishing characteristics of modern orthodontics. PMID- 8507027 TI - Comparison of three self-applied topical fluoride preparations for control of decalcification. AB - The purpose of this study was to compare the effectiveness of a 1100 ppm fluoride toothpaste used alone, or together with a 0.05% NaF rinse used once daily or a 0.4% SnF2 gel applied twice daily, in controlling the decalcification that often accompanies orthodontic treatment. Ninety-five consecutively treated adolescent patients were matched for age and sex and assigned to one of these three regimens. Single blind assessments of decalcification were performed on all labial surfaces of all erupted teeth before appliances were placed and 3 months after appliances were removed. Because the first molars had the highest decalcification scores, data for the whole mouth and for first molars were analyzed separately. When pre-treatment levels of decalcification were subtracted from post-treatment values, significantly lower decalcification scores (p < 0.05) were found for both whole mouth and first molars in the rinse and gel groups as compared with the control group (toothpaste alone). Although the gel group consistently had less decalcification than the rinse group, this difference only approached statistical significance. These results indicate that twice daily use of a 1100 ppm fluoride toothpaste and either a once-daily 0.05% NaF rinse or a twice-daily 0.4% SnF2 gel provides additional protection against decalcification beyond that achieved with toothpaste alone. PMID- 8507028 TI - Tooth formation in patients with oligodontia. AB - Oligodontia is defined as the congenital absence of many teeth. The aim of the present study was to evaluate tooth formation in patients with oligodontia who were missing six or more teeth. The oligodontia sample was compared to a control group matched for race, sex and age. Calcification stages of the teeth of the left side of the mandible were rated. Patients with oligodontia showed a tendency for delayed tooth formation. Significant differences in tooth formation were found between males with oligodontia and the control group for several stages of tooth formation. In females only stage 5 of the second mandibular molar showed a significant difference. Because of the great individual variation in tooth formation in patients with oligodontia, tooth formation in patients with oligodontia should be individually examined before starting treatment. PMID- 8507029 TI - Variation of anatomical and centroid points in the human fetal skull. AB - To overcome the problem of variation of reference points in cephalometric analysis two methods have been used: 1) fixed relations between consistently recognizable anatomical points and 2) centers of gravity. The linear distance between each point and every other point was calculated from their coordinates measured on radiographs of 60 fetuses (49-212 mm crown-rump length). For each distance between every permutation of points the variance was calculated for the series of 60 fetuses. The sum of the variances for each individual point against all other points was added together and the mean variance for each point derived by dividing by the total number of points. On the basis of mean variance the centroid of the total skull outline showed least variation and was therefore the most stable point measured. This was closely followed by the origin of the coordinate reference grid based on fixed relations theory. All the centroid points showed less variation than the anatomical points upon which the origin of the grid was based. PMID- 8507030 TI - Acute TMJ versus chronic TMJ. PMID- 8507031 TI - Sexual dimorphism in normal craniofacial growth. AB - The purpose of this investigation is to re-evaluate an existing sample of Caucasian individuals, of mostly Northern European ancestry and undefined ethnic origins, who have been characterized as having excellent occlusions and balanced facial proportions (from a subjective assessment). The focus is the emergence of sexual dimorphism in the skeletal and dental relationships. Serial lateral cephalograms of 51 subjects were obtained from the Bolton-Brush Study at ages 6, 9, 12, 14, 16 and 18 yrs. At each age, the records of 16 males and 16 females were selected. Cephalometric evaluation indicated that the length of the anterior cranial base was larger in males but the cranial base angle was similar for both sexes at all age intervals studied. The effective lengths of the maxilla and mandible were similar in both sexes up to 14 years; thereafter in females this length remained relatively constant while in males it increased. The direction of facial growth was similar for both sexes, with a tendency towards a more horizontal growth pattern in females. PMID- 8507032 TI - A comparative study using the Occlusal Index and the Index of Orthodontic Treatment Need. AB - Assessment of malocclusion is important for documentation of the prevalence and severity of malocclusion in population groups. Such information is needed in Hong Kong where less than 25 qualified orthodontists serve a population of about 6 million citizens. The objective of the present study was to compare the Occlusal Index (OI) and the Index of Orthodontic Treatment Need (IOTN) when used to assess orthodontic treatment needs in a local population. Only a weak association (Spearman's correlation coefficient = 0.31) was found between the two indices. The shortcomings of both indices are discussed. Neither OI nor the IOTN is perfect, but using the IOTN is less time consuming, making the study of a large population group more practical. PMID- 8507033 TI - Maxillary bonded retention. PMID- 8507034 TI - Nickel-titanium spring properties in a simulated oral environment. AB - A study of nickel-titanium springs was undertaken to determine whether their mechanical properties are affected by prolonged exposure to a static, simulated oral environment. Stainless steel springs and polyurethane elastic chains were also studied for comparison. The springs were elongated to twice their rest length and held at that length while immersed in artificial saliva at body temperature for 0, 2, 4 or 6 weeks. Plots of force vs. deformation were made as the springs were stretched from rest length to three times that length and then relaxed back to rest. Nickel-titanium springs suffered no degradation of their spring properties in the simulated oral environment. In contrast, stainless steel springs became slightly more compliant to stretching, and polyurethane elastics lost a large portion of their force-generating capacity. These findings confirm and extend earlier reports which indicate that nickel-titanium is a preferred material for many orthodontic applications. PMID- 8507035 TI - Laser etching of enamel for direct bonding. AB - The application of laser irradiation to etch dental enamel in preparation for direct bonding of orthodontic appliances has been studied. Forty extracted human teeth were divided into four groups of 10 teeth. Within each group, five teeth were subjected to a 30 sec acid etch of the buccal enamel surface; the other five in each group were etched with a laser. Four power settings on the laser etching unit were used: 80mJ, 1W, 2W and 3W. After etching, brackets were adhered to the prepared buccal enamel surfaces with composite resin. Shear bond strength was tested 7 days later. The findings showed that an acceptable shear bond strength, viz. > or = 0.6 kg/mm, could be achieved at laser power settings of 1 to 3W but not at the lowest setting (80 mJ). However, the mean shear bond strengths obtained with laser treatment of the enamel at 80mJ, 1W and 2W were lower (p < 0.01 or 0.001) than that achieved with acid etching. PMID- 8507036 TI - Allergy to stinging insects. PMID- 8507037 TI - Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47-year-old woman. PMID- 8507038 TI - Proud of the past: planning for the future. PMID- 8507039 TI - Suppression of an antibody to adenosine-deaminase (ADA) in an ADA-deficient patient receiving polyethylene glycol modified adenosine deaminase. AB - An adenosine deaminase (ADA) deficient patient with severe combined immunodeficiency (SCID) developed resistance to therapeutic injections of bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year-old girl was diagnosed as having partial ADA deficiency at age 7 years, and was started on bovine conjugated PEG-ADA at age 15 years. The weekly dose of 15 U/kg led to clinical improvement with resolution of sinusitis and bronchitis within 2 months and normalization of some T cell functions. After 5 months, however, she developed an inhibitory antibody to ADA, became refractory to treatment with PEG ADA, and clinically and immunologically deteriorated. This antibody was successfully suppressed over a 4-month period with a combination of prednisone (2 mg/kg/day), intravenous immunoglobulin (2 g/kg/dose), and discontinuing the PEG ADA injections for 7 weeks. The PEG-ADA injections were then restarted at a higher dose (20 U/kg/dose, twice a week). With the suppression of the inhibitory antibody, her clinical and immunologic status improved to previously achieved level. She has subsequently continued treatment for over 36 months, receiving a single weekly dose of PEG-ADA (20 U/kg/week) with sustained clinical and immunologic improvement, including weakly positive antigen-specific T cell proliferative responses to tetanus and Candida. PMID- 8507040 TI - Reduced responses of peripheral blood lymphocytes to heat-denatured food antigens in food-sensitive atopic dermatitis. AB - Although some patients with food-sensitive atopic dermatitis exhibit allergic symptoms to certain raw foods, they do not exhibit or scarcely exhibit allergic symptoms to boiled or cooked foods. In this study, although peripheral blood mononuclear cells responded to raw food antigens (ovalbumin or bovine serum albumin), the proliferative responses of peripheral blood mononuclear cells were reduced in heat-denatured food antigen-stimulation, in the hen egg- or cow milk sensitive patients with atopic dermatitis who did not exhibit or scarcely exhibited allergic symptoms to the boiled or cooked foods although the patients exhibited allergic symptoms to the raw foods. Our results show that proliferative responses of peripheral blood mononuclear cells to heat-denatured food antigens are good parameters for diet counseling in food hypersensitivity. PMID- 8507041 TI - Ubiquitous presence of cat allergen in cat-free buildings: probable dispersal from human clothing. AB - Fel d I has been found in almost all houses investigated, including those in which cats have never been present. These observations have not been explained. We measured Fel dI in samples of carpet dust from ten newly built model homes, 14 occupied homes, six allergists' offices, five hospital corridors, and three shopping mall stores. We also measured Fel d I on T-shirts of persons with and without cats. Measurable amounts of Fel d I were found in all the dust samples. Fel d I found in older model homes exceeded that found in newer model homes (P < .05). The amounts of Fel d I found in allergists' offices, hospital corridors, and retail stores were similar to the amounts found in occupied homes without cats. Fel d I was found in all T-shirts sampled and increased with increasing exposure to cats. Our findings confirm and extend previous reports of the ubiquitous presence of cat allergen and are consistent with the hypothesis that Fel d I is carried into cat-free buildings on the clothing of people exposed to cats. PMID- 8507042 TI - Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis. AB - A 33-year-old Chinese woman with exercise-induced anaphylaxis after ingesting Chinese seafood noodle soup, was studied for skin test reactivity to food, histamine, and codeine. Prick skin tests were negative for shrimp, wheat, and chicken soup base, but were positive at 5 to 6 mm (wheal diameter) to the whole broth after it had been combined with the other ingredients. No significant (> 3 mm) wheals were observed in eight controls who were simultaneously tested with the broth. To assess the role of exercise, three series of skin tests were performed with histamine, codeine, and whole broth before and after aerobic exercise on two occasions. Codeine elicited consistent increases in wheal size after exercise compared with pre-exercise skin tests. Histamine and whole broth wheal sizes did not increase significantly. Three control subjects also had codeine and histamine skin tests before and after exercise, No exercise associated increases were noted for codeine. Potential insights into mast cell abnormalities in exercise-induced anaphylaxis may be gained by skin testing patterns with codeine and other mast cell degranulating agents. PMID- 8507043 TI - Compliance with allergen immunotherapy. AB - Immunotherapy has been used for the treatment of allergic rhinitis since the turn of this century. The purpose of this study was to assess the compliance with immunotherapy in a medical center. The charts of 315 patients aged 5 to 18 years, who were prescribed immunotherapy for treatment of allergic rhinitis for at least 1 year before the study, were selected by computer and reviewed. The first analysis consisted of using a log-linear analysis in order to investigate the relationship between source of payment (private or nonprivate), gender, and race. All main effects and interactions were entered into the model (P < .01). The second analysis consisted of using a log-linear analysis to investigate the relationship between the presence/absence of pollen, mold, mite, and animal IgE antibodies, and compliance (model, P < .05). Two hundred fifty-eight patients were private and 57 were nonprivate. Fifty-nine percent (n = 152) of private patients and 46% (n = 26) of nonprivate patients were compliant. Of the 315 patients with allergic rhinitis, 52 also had asthma and 34 had atopic dermatitis. Sixty-one percent of the asthmatic patients and 47% with atopic dermatitis were compliant. Compliance was not increased by the number of allergens to which a patient was allergic. Males were slightly more compliant than females, caucasians were more often private patients and non-whites were more often nonprivate patients. Private patients were more complaint with immunotherapy than nonprivate patients. PMID- 8507044 TI - Latex hypersensitivity: a case study. AB - We report 16 cases of latex allergy and the diagnostic methods used to determine sensitivity. By history, eight had usually experienced anaphylaxis during operative procedures, and eight experienced contact urticaria. Skin prick tests were positive in all subjects and negative in ten controls. In vitro analysis by ELISA for latex-specific IgE was positive in only three subjects. No adverse reactions occurred during testing. We conclude that prick skin testing is the preferred diagnostic method, and that the in vitro method used in this study has an unacceptable lack of sensitivity. PMID- 8507045 TI - Methacholine inhalation challenge. Practical consequences of using duplicate spirograms after each concentration. AB - Several studies have shown that during bronchial provocation tests with pharmacologic agents, a prior deep inspiration causes transient bronchodilatation in normal subjects and patients with allergic rhinitis. We investigated the influence of using two consecutive spirograms after each methacholine concentration on the results of methacholine inhalation challenge. Methacholine inhalation challenge was performed in 70 nonsmoking subjects (26 with current asthma, 23 asymptomatic asthmatic patients and 21 patients with allergic rhinitis). The aerosols (PBS, followed by twofold increasing concentrations of methacholine from 0.095 to 50 mg/mL) were inhaled by tidal breathing for two minutes; after two minutes of aerosol inhalation, the subject performed two forced vital capacity maneuvers, 30 to 40 seconds apart. Separate dose-response curves were constructed from FEV1 values of the first and second spirogram. The PC20FEV1 (provocative concentration of methacholine required to produce a 20% fall in FEV1) was calculated from the log dose-response curves (first and second spirogram). The PC20 values obtained from the first (PC20-1) and second (PC20-2) spirogram were not significantly different in patients with current asthma, but the PC20-2 values were higher than the PC20-1 values in asymptomatic asthmatic patients (P < .01) as well as in patients with allergic rhinitis (P < .01). On the other hand, the PC20-2 values were one doubling concentration of PC20-1 values in one current asthmatic patient, one asymptomatic asthmatic patient and five patients with allergic rhinitis. We conclude that the choice of the first or second FEV1 obtained after each methacholine concentration significantly modifies the PC20 in asymptomatic asthmatic patients and patients with allergic rhinitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507046 TI - Pine pollen allergy in northern Arizona. AB - Allergy to pine trees is generally held to be rare and clinically insignificant. Skin test sensitivity to pine pollen antigen was found in 12 of approximately 826 (1.5%) atopic patients in a northern Arizona private allergy practice. There were five women and seven men and their ages ranged from 6 to 59 years. All were residents of the pine tree area for at least 2 years. All 12 reacted to the antigen of the predominant ponderosa pine and five also reacted, usually less strongly, to Colorado pinyon pine. Eight patients had spring season rhinoconjunctivitis and four others had perennial symptoms. Four of the 12 also had asthma. Some patients had clinical symptoms coinciding with pine pollen season. PMID- 8507047 TI - Reactivity of carrot-specific IgE antibodies with celery, apiaceous spices, and birch pollen. AB - Although carrot allergy is not well recognized in North America, the celery carrot-mugwort-spice syndrome is well known in Europe. In the current study, cross reactivity of carrot, stalk celery, and spices, all members of the Apiaceae and birch pollen was assessed with serum from a patient reporting raw carrot induced, raw stalk celery-induced, or spice-induced laryngeal edema and bronchospasm. By RAST inhibition, some cross-reactivity was demonstrated between raw carrot and stalk celery and other members of the Apiaceae. Immunoprint inhibition revealed common allergic epitopes on a 17-kD band shared by carrot, celery, and birch pollen. The results suggest that subjects sensitized to carrot may also have allergic reaction to other vegetables of spices of the Apiaceous family. Furthermore, carrot hypersensitivity can be associated with birch pollen allergy. PMID- 8507048 TI - Effects of calcium channel blockers in asthma. PMID- 8507049 TI - Reconstructing the evolution of mind. AB - Since Darwin, the idea of intellectual continuity has gripped comparative psychology. Psychological evolution has been viewed as the accumulation of gradual changes over time, resulting in an unbroken chain of mental capacities throughout the diversity of life. Some researchers have even maintained that no fundamental psychological differences exist among species. An alternative model argues that a rather profound new psychology related to mental state attribution may have evolved recently in the primate order. The author explores recent experimental research from chimpanzees, rhesus monkeys, and children that is consistent with this second model of psychological evolution. Drawing on the fields of developmental, comparative, and social psychology, as well as evolutionary and developmental biology, the author outlines a research agenda aimed at reconstructing the evolution of metacognition. PMID- 8507050 TI - The reality of repressed memories. AB - Repression is one of the most haunting concepts in psychology. Something shocking happens, and the mind pushes it into some inaccessible corner of the unconscious. Later, the memory may emerge into consciousness. Repression is one of the foundation stones on which the structure of psychoanalysis rests. Recently there has been a rise in reported memories of childhood sexual abuse that were allegedly repressed for many years. With recent changes in legislation, people with recently unearthed memories are suing alleged perpetrators for events that happened 20, 30, even 40 or more years earlier. These new developments give rise to a number of questions: (a) How common is it for memories of child abuse to be repressed? (b) How are jurors and judges likely to react to these repressed memory claims? (c) When the memories surface, what are they like? and (d) How authentic are the memories? PMID- 8507051 TI - Psychologists in the eyewitness world. AB - Over the past century, but especially over the past 20 years, psychological studies of eyewitness identification have been accumulating. Wells (1993, this issue) believes that the time is ripe to summarize the research on identification procedures, such as lineups and showups, that will minimize false identifications of innocent people and maximize accurate identifications of the guilty. Other experts in the field worry that there is still too big a leap from the laboratory work to the real world of crime. Identification research, many agree, has the potential for being one of the more useful arenas in which psychological science can make a difference in society. PMID- 8507052 TI - What do we know about eyewitness identification? PMID- 8507053 TI - The single indication for cystography in blunt trauma. AB - To define the indications for cystography in blunt trauma, two studies were completed. First, a 15-month retrospective evaluation revealed 26 patients with bladder trauma. All 26 patients presented with gross hematuria. This was followed by a randomized prospective study of all patients with blunt trauma. Patients were randomized to be evaluated with cystography for any degree of hematuria or the diagnosis of pelvic fracture versus those to be evaluated only for the presence of gross hematuria. Eleven patients had pelvic fractures and no hematuria. One hundred nine patients had microscopic hematuria and a 39 per cent incidence of coexistent pelvic fractures. Thirty-one patients had gross hematuria and a 26 per cent incidence of pelvic fracture. Bladder injuries were seen only in this latter group. Cost analysis of the prospective study revealed a potential savings of $26,322 if gross hematuria had been the sole indication for cystography in blunt trauma. This approach has potential cost savings and, more importantly, will not compromise the quality of trauma care. PMID- 8507054 TI - Predictors of mortality in penetrating cardiac injury. AB - Forty-eight cases of penetrating cardiac trauma seen at the Medical University of South Carolina between 1979 and the present were reviewed retrospectively. Age, race, sex, Champion trauma score, cardiac chamber injured, associated injuries, weapon, circumstances, and means of transport were recorded and analyzed to define predictors of mortality. Overall mortality was 56 per cent. The median trauma score of survivors was significantly higher than the median trauma score of nonsurvivors, P = 0.0001. The median age of survivors was significantly lower than the median age of nonsurvivors, P = 0.046. Sex, race, the chamber injured, weapon, circumstances, and mode of transport were not significantly different between survivors and nonsurvivors. Survival did not change significantly during the study period. Mortality compares favorably with that of other series. PMID- 8507055 TI - Battered children with duodenal avulsion and transection. AB - Two cases of severe duodenal injury following child abuse are presented. One avulsion injury required pyloric exclusion. Both 2-year-old children survived without anastomotic complications. Survival after these injuries rests on the ability to apply multiple techniques for duodenal reconstruction, as well as the recognition of individual cases of abuse-associated malnutrition. A high index of suspicion following abuse-associated blunt abdominal trauma will prevent diagnostic delay in children with retroperitoneal duodenal injuries. PMID- 8507056 TI - Sustained pulmonary hypertension in surgical patients. AB - Twenty-two consecutive critically ill surgical patients who had a Swan-Ganz thermodilution catheter inserted as part of their intensive care unit therapy were studied prospectively. Patients were divided into two groups. Group I consisted of 17 patients whose pulmonary artery diastolic pressure minus pulmonary artery wedge pressure (PADP-PAWP) gradient was less than 5 mm Hg or if greater than 5 mm Hg persisted for less than 12 hours. Group II was composed of 5 patients whose PADP-PAWP gradient was greater than 5 mm Hg for at least 12 hours or more. The two groups were equally matched in terms of risk factors that predispose to an elevated gradient or factors that falsely lower the gradient. Nine other physiologic parameters were measured in patients in Group II during the period of the elevated gradient and were compared with the same parameters measured in patients in Group I. An elevated pulmonary vascular resistance was the only parameter associated with an elevated gradient. An elevated PADP-PAWP gradient greater than 5 mm Hg that persisted for 12 hours or more was associated with a 60 per cent mortality rate. PMID- 8507057 TI - The role of sigmoidoscopy in the management of gunshot wounds to the buttocks. AB - The charts of all patients (n = 70) admitted over 26 months after sustaining a gunshot wound to the buttocks were reviewed to assess the role of physical examination, routine radiologic studies, and sigmoidoscopy in the evaluation of these patients. There were 68 men and 2 women. Sixteen patients underwent sigmoidoscopy, which demonstrated a rectal injury in 7. Six of these patients had other abnormalities on either physical examination or plain pelvic radiographs that would have otherwise led to operation. There were no missed injuries and no morbidity in the remaining patients that were managed without sigmoidoscopy. Indications for sigmoidoscopy were gross blood on rectal examination in 2, bullet path with proximity to the rectum in 13, and persistent abdominal pain in 1. All patients with gross blood on rectal examination (n = 5) and blood at the urethral meatus (n = 2) had visceral injuries. One patient underwent celiotomy for an injury at 15 cm that was noted on sigmoidoscopy performed because the bullet trajectory was in proximity to the rectum. Sigmoidoscopy can be performed selectively in patients sustaining a gunshot wound to the buttocks when the proximity of the wound to the rectum is in doubt. PMID- 8507058 TI - Immediate isolated interventricular septal defect from nonpenetrating thoracic trauma. AB - Interventricular septal defect following nonpenetrating trauma is a rare event. In a review of 207,548 autopsies, only 30 (0.01%) cases of traumatic ventricular septal defects were noted, and only 5 (0.002%) were isolated. We report an isolated interventricular septal defect following nonpenetrating trauma. PMID- 8507059 TI - An unusual injury of the sigmoid colon produced by seat belt trauma. AB - It is well documented that use of seat belts will reduce the incidence and severity of injuries associated with motor vehicle accidents. However, seat belts themselves can produce serious injury, particularly if worn incorrectly. Three cases of an unusual sigmoid colon injury produced by seat belt trauma are reported. Each patients physical exam findings, as well as the anatomy and histology of the injury, are presented to illustrate the deceptive nature of this injury, and to stress the importance of an accurate diagnosis and management. PMID- 8507060 TI - Improving outcome from extremity shotgun injury. AB - The charts of 124 consecutive patients with extremity shotgun injuries managed over an 8-year period were reviewed to assess the results of a uniform protocol. This consisted of liberal use of arteriography, prompt exploration, wide debridement or fasciotomy, and frequent operating room dressing changes for large wounds. Thirty-three patients had arterial injuries and 16 had major venous injuries. Twenty patients had major soft tissue wounds and there were 15 significant long bone injuries. Results overall were excellent with over 95 per cent of patients retaining an intact and functional limb. Of the six limb amputations, three were done primarily and three were performed for late septic complications. Two of these late amputations were done following inadequate initial revascularization at referring hospitals. Early wound closure, liberal use of arteriography and fasciotomy, early fracture stabilization, and repair of all significant vascular injuries contribute to a successful outcome in patients with extremity shotgun wounds. PMID- 8507061 TI - Negative trauma celiotomy. AB - A retrospective review of 525 consecutive exploratory celiotomies for abdominal trauma occurring between January 1987 and June 1990 in an urban trauma center was conducted. One hundred-fifteen patients sustained blunt abdominal trauma (21%), and 410 patients sustained penetrating abdominal trauma (78%). Penetrating injuries included 260 gunshot wounds and 150 stab wounds. Patients were divided into three groups: Group A (16%), no visceral injuries identified at exploration (true negative); Group B, positive operative findings at celiotomy requiring no operative repair (10%) (nontherapeutic celiotomy); and Group C (74%), injuries encountered requiring operative repair (true positive). A positive exploration rate of 90 per cent with blunt trauma is acceptable using diagnostic techniques currently available. Similarly, a positive exploration rate of 85 per cent in gunshot wounds warrants our continued use of mandatory celiotomy. A 36 per cent combined incidence of true negatives and nontherapeutic celiotomies (Group A and B) is unacceptably high. To reduce this high incidence will require improved clinical surveillance and the controlled implementation of newer diagnostic techniques. PMID- 8507062 TI - Missed injuries associated with spinal cord trauma. AB - Spinal cord trauma frequently results from high energy vehicular accidents which produce multisystem trauma. Because of the priorities of resuscitation, other injuries may escape early diagnosis. This study was undertaken to examine the extent and implications of "missed injuries" associated with spinal trauma. We reviewed the charts of 24 patients (23 men, one woman) with spinal cord injuries, who presented during a consecutive 9-year period. The median age was 31 years. Two patients died. There were 13 cervical, 10 thoracic, and one lumbar injuries. Blunt trauma was responsible for injuries in 18 cases, other mechanisms were the cause in six cases. The average initial Glasgow coma score was 13 +/- 0.8 (SEM). Average revised trauma score (RTS) was 6.7 +/- 0.3 (SEM). Other injuries noted at the time of presentation included: head and neck (8), thoracic (6), extremity (2), and major vascular (1). There were 11 initially undiagnosed injuries in 10 patients (42%); six were "nonspinal" and five were "spinal," diagnosed between 1 and 30 days after admission. Average trauma scores were the same among those with and without missed injuries. Missed spinal injuries included: fractures of C5-6 (2), C4 (1), T7 (1), and L1 presenting as a progressive deficit (1). Nonspinal injuries were: pneumothorax (3), hemopneumothorax (1), paralyzed hemidiaphragm (1), and renal contusion (1). Prolonged hospital stay and/or the need for additional surgery were the most common sequelae of delayed diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507063 TI - The utility of color flow Doppler examination in penetrating extremity arterial trauma. AB - Recent reports from our institution have demonstrated the safety of nonoperative management of minimal arterial injuries. The purpose of this pilot study was to evaluate whether color flow Doppler (CFD) examination could detect minimal arterial injuries caused by penetrating extremity trauma. Twelve patients with minimal arterial injuries identified by arteriography were treated nonoperatively. Each also underwent color flow examination. Seven of 12 arteriographic abnormalities were detected by color flow examination. Two intimal injuries (brachial artery, superficial femoral artery (SFA)), one small (1 mm) pseudoaneurysm (popliteal artery), and two minor vessel occlusions (interosseous artery, branch off SFA) were not detected. These preliminary data suggest that color flow scans may be less sensitive than arteriography in the detection of clinically insignificant lesions such as small intimal defects or small vessel occlusions. Despite this, CFD examination was successful in detecting more significant lesions such as pseudoaneurysms, arteriovenous fistulae, and major vessel occlusions. This is relevant since these lesions may require immediate intervention. These findings suggest the possibility that color Doppler sonography may be able to sequentially monitor these lesions to determine if they resolve or progress. If progression is documented they may require surgical correction. Further prospective studies must be performed to assess whether color flow Doppler examination can supplant arteriography in patients at low or intermediate risk for arterial injury following penetrating arterial trauma. PMID- 8507064 TI - Exposure of buttock burn wounds to stool in scald-abused infants and children: stool-staining of eschar and burn wound sepsis. AB - Between July 1, 1987 and June 30, 1990, 30 consecutive deliberately scalded children with buttock involvement were prospectively studied. Mean age was 22.5 months. Mean burn size was 18.1 per cent TBSA (total body surface area). Thirty per cent (n = 9) had diarrhea complicate their wound or autograft care. For those requiring surgery for their buttock/perineal burns, various combinations of preoperative mechanical bowel prep, oral antibiotics, postoperative occlusive intrarectal catheter, nothing-by-mouth, and rigid postoperative positioning did not protect buttock wounds and autografts from stool. Four patients had stool staining of the superficial burn wound exudate, none of whom developed burn wound sepsis or died. Four (13.3%) patients with a mean burn size of 32.3 per cent TBSA, diarrhea, and burns involving the buttock, perineum, and external genitalia died of burn wound sepsis, three of whom had deep stool staining of their burn wound and Gram-positive bacteremia. Buttock burn wounds should be examined carefully and frequently for the presence of deep stool staining, an ominous predictor of burn wound sepsis and death. Such wounds, if present, should be emergently excised. PMID- 8507065 TI - Seroprevalence of human immunodeficiency virus in admitted trauma patients at a southeastern metropolitan/rural trauma center. AB - Human Immunodeficiency Virus (HIV) seropositivity was prospectively evaluated for trauma patients admitted to Memorial Medical Center between September 1989 and August 1990. Epidemiologic data, HIV risk factors, and opportunity for body fluid exposure were compiled for 520 admitted trauma patients 15 years of age or older who met inclusion criteria. Serum samples were obtained from initial laboratory tests. Patient identifiers were removed, and matching blinded numbers were placed on patient serum and data forms. Centers for Disease Control laboratories tested for HIV with the enzyme-linked immunosorbent assay method. The Epi-Info (Version 5.01, 1990) software package was used for statistical analysis of epidemiologic data. Results showed HIV seropositivity of admitted trauma patients to be 0.96 per cent (5/520). HIV seroprevalence among young black males from our urban area who were injured during violent aggression was 3.5 per cent. Management of 80 per cent of patients resulted in opportunity for body fluid exposure. Illicit drug use was reported by 15 per cent; 7.5 per cent gave a history of transfusion since 1977; 3 per cent identified high risk sexual partners; three patients reported homosexual activity. Two patients denied risk factors, but were HIV-seropositive. The results indicate that HIV exposure is a potential hazard to health care workers and that HIV risk factors alone are not reliable in identifying the HIV positive patient. PMID- 8507066 TI - Surgical management of pediatric renal trauma: an urban experience. AB - This study was undertaken to review our operative experience in the management of pediatric renal trauma. Over a 2-year period (August 1988 to August 1990) 25 of 60 children undergoing celiotomy sustained renal injuries. There were 22 boys and three girls ranging in age from 5 to 18 years. Eighty-four per cent were victims of gunshot wounds, 12 per cent were stabbed, and 4 per cent sustained blunt trauma. The 25 injured children sustained a total of 45 individual organ injuries. Only 16 per cent required a nephrectomy, while the great majority (84%) were managed with renal sparing procedures. When we compared survivors to nonsurvivors, there was more thoracic and vascular injury along with more blood transfusion requirements in nonsurvivors. There was no statistical difference in Pediatric Trauma Score (PTS) between survivors and nonsurvivors (9.8 +/- 0.26 vs 9.5 +/- 1.5). Preoperative intravenous pyelographies (IVPs) performed in 52 per cent of all patients demonstrated the site of injury, presence of contralateral function as well as the anatomic position of the kidneys. We conclude that renal injury is common following penetrating abdominal trauma in childhood, however, these injuries can be managed by early operation with renal sparing procedures. There is a high incidence of associated intra-abdominal injury in those who have sustained penetrating renal trauma, but mortality is more common in patients sustaining associated thoracic and vascular injuries. An IVP should be performed, even in the absence of hematuria, when trauma trajectory strongly suggests urologic injury. This study also illustrates the sharp rise in drug-related urban violence with an associated increase in pediatric renal trauma. PMID- 8507067 TI - Reduction of neophobia in humans by exposure to novel foods. AB - In the first part of a two-part study we attempted to determine whether individuals consider novel foods (in comparison to familiar foods) to be dangerous and expect to dislike their tastes, and, if so, whether willingness to eat them is systematically related to the degree of perceived danger and expected disliking. A series of multiple regression analyses revealed that disliking and danger are both good predictors of willingness to try novel foods while willingness to try familiar foods is predicted only by disliking. In the second part of the study we examined experimentally the effect of "forced" exposure to novel foods on subsequent neophobia. Some subjects were required to taste seven novel foods while others tasted seven similar familiar foods; all subjects were then given the task of selecting for tasting one member of each of 11 pairs of foods. The pairs were comprised of one novel and one familiar food (different from those used in the exposure to novelty manipulation), and number of novel choices was the measure of neophobia (with fewer choices indicative of greater neophobia). The results were discussed in terms of the usefulness of considering food neophobia as a phobia in the sense in which clinical psychologists use the term. PMID- 8507068 TI - Prior exposure to low or high fat milk enhances naloxone anorexia in rats. AB - Opioid peptides have been implicated in reward-related components of eating, especially with fatty and sweetened foods. This study examined the effect of pre exposure of rats to milk on the subsequent anorexic effect of naloxone in a separate daily mash intake test. Rats were given constant access to either skimmed or whole milk for 15 days, in addition to normal diet. A third (control) group received only the normal diet. Subsequently, all groups received 0, 0.125, 0.5 and 1.0 mg/kg naloxone prior to their daily mash intake test. Naloxone caused dose-dependent reductions in mash intake in all groups, but this effect was significantly greater in the group with whole milk than in controls, with the group with skimmed milk intermediate. Daily intakes of milk were similar with skimmed and whole milk, and milk intake in separate two-bottle choice tests provided no evidence for overall preferences for either solution. These results suggest that prior exposure to milk enhances opioid involvement in feeding, and possible mechanisms for this are discussed. PMID- 8507069 TI - Effect of activation of the serotoninergic system during prolonged starvation on subsequent caloric intake and macronutrient selection in the Zucker rat. AB - Starvation or dietary restriction are known to modify post-fasting dietary self selection. We have examined the effects of activation of the serotoninergic system and food deprivation on macronutrient self-selection following a period of starvation. Rats were starved for 4 days and either treated or not with dl fenfluramine or fluoxetine. Starved untreated animals showed a post-fasting anorexia and an increased preference for carbohydrate intake, even though lipids remained the preferred source of calories. Treatment with fenfluramine or fluoxetine increased post-fasting anorexia, abolished the preference for carbohydrates and decreased lipid intake. Fluoxetine, but not fenfluramine, resulted in decreased protein intake as well. Following a 2-day refeeding period ad libitum, during which the animals were not treated with drugs, the anorectic effect of fenfluramine disappeared but that of fluoxetine remained unchanged. In addition, we noted that at an equimolar dose to dl-fenfluramine (100 mumol/kg/day) fluoxetine treatment resulted in the death of all the animals in the group by the second day of refeeding; no deaths were observed in any of the other groups. In conclusion, we confirm a post-starvation anorexia and increased carbohydrate intake following long-term fasting. In addition we show that activation of the serotoninergic system abolishes the increase in carbohydrate intake and potentiates post-starving anorexia. PMID- 8507070 TI - Children's lunch intake: effects of midmorning snacks varying in energy density and fat content. AB - To determine the effects of preloads differing in energy density and fat content on subsequent lunch intake, 24 preschool children consumed 113 g ice-cream preloads as mid-morning snacks (containing 0, 12, or 18 g of fat, and 4 g of protein), followed nearly 2 h later by an ad libitum lunch consisting of a variety of foods. A fat-free baseline preload, consisting of dry cereal and apple juice, was also included. The baseline, fat-free, medium and high-fat preloads contained 334, 740, 953, and 1150 kJ per serving. All three ice-cream preloads produced significant but equivalent suppression of ad libitum lunch intake relative to baseline; lunch intake was not related to the fat content or energy density of the ice-cream preloads. Compensation at lunch was not macronutrient specific; children did not increase their fat intake at lunch following the fat free preload. As energy and fat content of the preloads increased, children consumed significantly fewer foods at lunch, confirming previous findings. These changes in the variety of foods consumed were related to preference: regardless of preload, children continued to consume their preferred foods, while non preferred foods tended to be eliminated following the higher energy preloads. Because compensation for energy was incomplete, energy intake of meals plus snacks increased with the energy content of the preload. Additional research is required to determine whether manipulating the fat and energy content of snacks produces similar effects when the unit of analysis is the child's total daily diet, rather than a single meal. PMID- 8507071 TI - Ethanol as an energy source in humans: comparison with dextrose-containing beverages. AB - Six subjects participated in a residential study assessing the effects of consuming beverages containing energy derived from ethanol or dextrose on total energy and macronutrient intake. On certain days, subjects had to consume four beverages containing a total of approximately 2400 or 4600 kJ, equivalent to 22% and 42% of energy intake under conditions in which no-beverages were required. Each of four conditions (2400 kJ ethanol, dextrose; 4600 kJ ethanol, dextrose), and a no-beverage control condition was examined for 2 days. Subjects compensated for approximately 37% of the energy contained in the beverages such that total intake increased by 13% under the 2400 kJ conditions and 27% under the 4600 kJ conditions. There was no differential effect of ethanol content on energy intake. Cumulative intake curves indicated that caloric compensation was minimal following the consumption of beverages in the evening. While all of the beverage conditions significantly decreased energy intake derived from carbohydrate, the proportion of energy derived from fat, carbohydrate, and protein without the energy content of the beverages was essentially unaffected by dextrose- or ethanol-containing beverages. These results suggest that the effects of ethanol on intake of other foods can be accounted for by the energy content of ethanol as a beverage and by ethanol consumption in the evening when there is little time for daily caloric compensation, rather than by the pharmacological effects of ethanol. PMID- 8507072 TI - Verruca vulgaris. Treatment with natural interferon alfa using a needleless injector. PMID- 8507073 TI - Are viral warts seen more commonly in children with eczema? AB - BACKGROUND AND DESIGN: We sought to test the hypothesis that warts are seen more commonly in individuals with eczema by analyzing skin examination data from a national birth cohort study of 9263 British children born between March 3 and 9, 1958. RESULTS: Warts were seen less frequently in those with visible eczema at ages 11 and 16 years (relative risk, 0.60; 95% confidence intervals, 0.37 to 0.95; P = .03). This inverse association persisted after adjustment for potential confounders and was consistent within each age and sex group for children with a history of eczema who did not have visible eczema at the time of examination and for children with asthma/wheezy bronchitis regardless of eczema status. Visible acne or psoriasis was not associated with a decreased prevalence of warts. CONCLUSIONS: These findings contradict previous suggestions of an increased risk of viral warts in atopic eczema and raise new questions regarding the role of cell-mediated immunity in atopic subjects. PMID- 8507074 TI - Impaired antigen presentation in toxic epidermal necrolysis. AB - BACKGROUND AND DESIGN--The pathophysiology of toxic epidermal necrolysis (TEN) remains largely unknown. Toxic epidermal necrolysis is considered a hypersensitivity reaction to drugs, but direct evidence of an immunologic mechanism is still lacking. Lymphopenia and a decrease in the numbers of circulating CD3- and CD4-positive lymphocytes have been reported in acute phase, but, to our knowledge, no study of cellular immune functions of patients with TEN has been reported so far. Herein, we investigated several T-cell functions in a series of 11 patients with TEN. Peripheral blood mononuclear cells (PBMC) obtained in the acute phase were tested together with PBMC obtained after the patient's recovery and compared with those of age- and sex-matched healthy control subjects. RESULTS--Phytohemagglutinin-induced proliferations and lymphocyte responses in allogeneic mixed lymphocyte reactions were not impaired in the acute phase compared with those after recovery in the same patients and with those in control subjects. In contrast, natural killer cytotoxicity and allogeneic cytotoxic responses were significantly decreased in early TEN. The most striking feature was the significantly impaired ability of acute-phase lymphoid cells to activate allogeneic T cells. Patient PBMC in acute-phase TEN did not inhibit the proliferation induced by patient PBMC after recovery, suggesting that their defect was not related to the presence of radioresistant suppressor cells. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on circulating peripheral blood lymphocytes was then assessed by immunoalkaline phosphatase staining and flow cytometry. Results showed decreased percentages of HLA-DR-positive mononuclear cells and a decreased density of HLA-DR antigens, mainly on monocytes, in acute-phase TEN. CONCLUSIONS--These results demonstrate that peripheral blood lymphocytes of patients with TEN have an impaired ability to activate allogeneic T cells. This defective antigen presentation is not secondary to the presence of suppressor lymphocytes, but it is probably related to a decreased expression of HLA-DR antigens on circulating mononuclear cells in acute-phase TEN. PMID- 8507075 TI - Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin. AB - BACKGROUND AND DESIGN: When the epidermal permeability barrier is perturbed with acetone, transcutaneous water loss returns to normal over 24 hours in parallel with the reappearance of stratum corneum lipids, derived from secreted lamellar bodies and accelerated lipid synthesis. Prior studies have demonstrated a separate requirement for cholesterol, fatty acid, and ceramide synthesis for barrier homeostasis, but the requirement for these lipids individually or together for barrier function is not known. We therefore applied these lipids alone or in various mixtures to acetone-treated hairless mouse skin and assessed barrier recovery. RESULTS: Ceramide and fatty acid alone, and their complex derivatives (cholesterol esters and cerebrosides), and two-component mixtures of fatty acid plus ceramide, cholesterol plus fatty acid, or cholesterol plus ceramide delayed barrier recovery. In contrast, complete mixtures of ceramide, fatty acid, and cholesterol allowed normal barrier recovery. Moreover, fluorescent-labeled cholesterol, fatty acid, and ceramide rapidly traversed the stratum corneum with uptake into the epidermal nucleated layers. Finally, incomplete, but not complete mixtures produce abnormal lamellar bodies, leading to abnormal stratum corneum intercellular membrane bilayers. CONCLUSIONS: (1) Topical applications of individual lipids or incomplete mixtures of lipids interfere with barrier recovery, while complete mixtures of cholesterol, fatty acid, and ceramide allow normal barrier repair; and (2) incomplete mixtures of topical lipids appear to inhibit barrier recovery at the level of the lamellar body resulting in abnormal intercellular membrane structures in the stratum corneum, abnormalities that do not occur when a complete lipid mixture is provided. PMID- 8507076 TI - p53 Protein expression in nevi and melanomas. AB - p53 Protein immunohistochemical expression is a wide-spread feature of the malignant phenotype; most melanomas are reported as p53 positive, while nevi are reported as p53 negative. We investigate a series of 75 benign nevi and 47 melanomas (40 primary and seven metastatic) to evaluate their pattern of p53 immunoreactivity with a panel of specific antibodies (PAb1801, PAb240, DO7, and CM1) in view of a possible diagnostic role of p53 immunostaining. Our results demonstrate that 15% of nevi show p53 immunoreactive nuclei (usually in less than 1% of the cells) and that 30% of melanomas show p53 immunoreactive nuclei (one case with 20% immunoreactive cells, six cases with 1% to 5% positive cells, and four cases with less than 1% positive nuclei). p53 Positivity was seen also in basal and suprabasal keratinocytes. p53 Positivity in nevi is at variance with literature data supporting that nevi are p53 negative. p53 Positivity in nevi and in epidermis may be related to mechanisms of DNA repair, apoptosis, or to a specific phase of the cell cycle. In our series, p53 expression in melanomas is not as frequent as reported in the literature. Population-based differences or differences in case selection and sample handling may account for the above discrepancies. The demonstration of p53 positivity in benign skin lesions greatly hinders the possibility of a diagnostic use of p53 immunostaining in dermatopathology. PMID- 8507077 TI - Floor-pattern salt-split skin cannot distinguish bullous pemphigoid from epidermolysis bullosa acquisita. Use of toad skin. AB - BACKGROUND AND DESIGN: Patients with epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP) can present with similar clinical features. These antigens have different phylogenetic origins. It was thought that sodium chloride split-skin immunofluorescence could reliably distinguish between BP and EBA. However, it has now been recognized that both diseases can present with a floor pattern fluorescence on salt-split skin. A simple method is required to distinguish these diseases. RESULTS: Serum specimens from two patients presenting with pruritic blisters showing a floor pattern immunofluorescence on salt-split skin were found to have positive fluorescence on toad skin that has the BP and not the EBA antigen. The diagnosis of BP in these patients was confirmed by a prompt response to treatment with systemic steroids. Electron microscopy showed a split at the lamina lucida. CONCLUSIONS: Bullous pemphigoid can present with a floor pattern immunofluorescence on salt-split skin. The use of the skin from invertebrates like the toad may help in distinguishing BP from EBA. PMID- 8507078 TI - Complete remissions in psoralen and UV-A (PUVA)-refractory mycosis fungoides-type cutaneous T-cell lymphoma with combined interferon alfa and PUVA. AB - BACKGROUND AND DESIGN--The optimal therapy for the mycosis fungoides type of cutaneous T-cell lymphoma has yet to be determined. Based on recent reports on the efficacy of high-dose interferon alfa in cutaneous T-cell lymphoma, we chose to test the hypothesis that systemic adjunctive therapy with low-dose interferon alfa along with psoralen and long-wave UV-A radiation (PUVA) could decrease the amount of PUVA necessary to achieve the best response, as well as improve the therapeutic effect of PUVA. Five patients with cutaneous T-cell lymphoma (mycosis fungoides type) were initially treated unsuccessfully with PUVA alone (three times a week for at least 3 months); PUVA was stopped, patients' diseases were re staged, then interferon alfa (3 x 10(6) U/d for 1 week, then 6 x 10(6) U/d for 1 week) was initiated 2 weeks prior to restarting PUVA. Responses to treatment were graded as complete remission (skin clear, or negative biopsy specimens of remaining dermatitic lesions), partial remission (> 50% improvement), progression (> 25% worsening), or no change (failure to qualify for other categories) at 4, 8, 12, and 16 weeks. OBSERVATIONS--After 3 to 5 months of treatment with PUVA thrice weekly, none of the patients treated with PUVA alone had achieved complete remission. By contrast, systemic adjunctive therapy with low-dose interferon alfa along with PUVA resulted in complete remissions in all five (100%) patients in an average of 3.2 months (in three patients, lesions were cleared by 3 months). Average of 107 additional joules (68% more) and 1.6 additional months of PUVA administered thrice weekly was required to achieve the best response attainable with PUVA alone compared with complete remissions achieved with combined interferon alfa and PUVA therapy. CONCLUSION: --These data indicate that patients with disease refractory to PUVA alone can achieve a complete remission if they restart treatment with PUVA in combination with well-tolerated low doses of interferon alfa. In addition, the duration of PUVA exposure can be reduced with the addition of low-dose interferon alfa to the conventional PUVA treatment of cutaneous T-cell lymphoma of the mycosis fungoides type in such patients. PMID- 8507079 TI - Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. AB - BACKGROUND AND DESIGN--Protein C is a vitamin K-dependent plasma protein that is converted to the serine protease activated protein C by the thrombin thrombomodulin complex. Activated protein C functions as a natural anticoagulant by inactivating the cofactors of the coagulation cascade, factors Va and VIIIa. Coumarin (warfarin)-induced skin necrosis is thought to be due to a rapid elimination of protein C relative to other vitamin K-dependent factors during the initial phase of oral anticoagulation. We have used a highly purified protein C concentrate to treat a patient with acquired protein C deficiency who developed skin necrosis during the initial phase of oral anticoagulant therapy. OBSERVATIONS AND CONCLUSIONS--During protein C concentrate therapy, no further skin lesions appeared, and the healing process of necrotic areas was facilitated. Replacement therapy with protein C concentrate appears to be safe and effective as an adjunctive treatment for coumarin-induced skin necrosis. PMID- 8507080 TI - Fibrillar protein deposits with tubular substructure in a systemic disease beginning as cutis laxa. AB - BACKGROUND: The homogeneous material found in the skin is commonly identified as amyloid. We describe a previously unknown disease that is caused by proteinaceous deposits and that does not fulfill the criteria of the earlier recognized amyloid diseases. OBSERVATIONS: The unusual deposits, which were initially found in the dermis, were ultrastructurally composed of fibrillar material with a tubular substructure. Immunohistologically, the material was tested using a large panel of antibodies, and the results revealed that it was unlike any commonly known proteinaceous material. The deposits later spread to other organs and disturbed the vital functions of the body. CONCLUSIONS: We describe a unique syndrome characterized by fibrillar extracellular deposits that was recognized and differentiated from other similar clinical syndromes by ultrastructural examination. Further biochemical analysis is necessary to identify the origin of the material. PMID- 8507081 TI - Interferon and Hillary Clinton. PMID- 8507082 TI - Coumarin-induced skin necrosis. PMID- 8507083 TI - Purpura as the presenting sign of an internal disease. Multiple myeloma. PMID- 8507084 TI - Multiple papules and plaques in a patient with ovarian carcinoma. Granulocytic sarcoma (GS) of the skin. PMID- 8507085 TI - Sudden onset of blisters and ulcerations in a healthy man. Toxic epidermal necrolysis (TEN). PMID- 8507086 TI - Purple toes and livido reticularis in a patient with cardiovascular disease taking coumadin. Cholesterol emboli associated with coumadin therapy. PMID- 8507087 TI - Inoculation of a cultured autologous epidermal suspension containing melanocytes in vitiligo. PMID- 8507088 TI - Acute paronychia apparently caused by Candida albicans in a healthy female. PMID- 8507089 TI - Lack of efficacy of a barrier cream in preventing rhus dermatitis. PMID- 8507090 TI - Fanconi's anemia with cutaneous amyloidosis. PMID- 8507091 TI - Partial reversal of canities in a 22-year-old normal Chinese male. PMID- 8507092 TI - Neutrophilic eccrine hidradenitis heralding the onset of acute myelogenous leukemia. PMID- 8507093 TI - Toxic epidermal necrolysis due to indapamide. PMID- 8507094 TI - Erythema chronicum migrans in Suzhou, China. PMID- 8507095 TI - Vulvar lichen planus treated with topical cyclosporine. PMID- 8507096 TI - Papilloma development in cyclosporine-treated patients. PMID- 8507097 TI - Heavy metal and selenium levels in endangered wood storks Mycteria americana from nesting colonies in Florida and Costa Rica. AB - Colonially-nesting birds often nest in coastal areas, along rivers, or near other bodies of water that also are potentially polluted from industrial, agricultural or urban development. The levels of heavy metals and selenium were examined in the feathers of young wood storks Mycteria americana nesting in Northeastern Florida and from adult and young storks nesting on the Tempisque River on the west coast of Costa Rica. There were no significant yearly differences among the chicks from Costa Rica. Concentration of mercury, cadmium, and lead were significantly higher in the chicks from Florida compared to those from Costa Rica. Adult wood storks at Costa Rica had significantly higher levels of lead, cadmium, selenium, and manganese than young from the same colony. PMID- 8507098 TI - Responses of hemocytes and gill tissues to sublethal cadmium chloride poisoning in the crab Paratelphusa hydrodromous (Herbst). AB - The hemocytic and gill tissue responses of the crab Paratelphusa hydrodromous (Herbst) to a wide range of sublethal concentrations of cadmium chloride (0.02 0.50 microM/L) were examined after a 30-day exposure using hemocyte counts (THC and DHC) and lamellar pathology. A continued reduction in the hemocyte counts and selective changes in the numbers of hyalinocytes and eosinophilic granulocytes was evident in the toxified crabs. Under sublethal stress, the hyalinocytes developed eccentric nuclei, granular cytoplasm and membrane blebs. Atypical shape, lobate nucleus, dense cytoplasmic deposits and granuloplasmic vacuoles were frequently observed in the granulocytes. Greater proliferation of prohemocytes and abnormal hemocyte morphology indicated cadmium-induced neoplastic transformation of hemocytopoietic organs. No major structural changes in the gills were noted at 0.02 microM CdCl2. Nodular gill disease (NGD), hemocytic hyperplasia and sloughing of walled off hemocytes were prominent lesions after 0.50 microM cadmium chloride exposure. PMID- 8507099 TI - Effects of bis(tri-n-butyltin)oxide in Japanese quail exposed during egg laying period: an interlaboratory comparison study. AB - The guideline no. 206 for testing of chemicals of the Organization for Economic Cooperation and Development (OECD) comprising an avian reproduction test using the Japanese quail (Coturnix coturnix japonica; Termminck and Schlegel 1849) as pair-hold test organisms has been applied in a version that reduced the treatment period to 6 weeks without any pretreatment. In the present study bis(tri-n butyltin)oxide, C.A. No. 56-35-9 (tributyltin oxide, TBTO) was examined by five participants in an interlaboratory comparison test. A comparable regimen of dosing was performed by all participants starting either with 24 or 60 mg/kg TBTO in the feed and ending with 150 or 375 mg/kg. Within this dose range no signs of toxicity in adults were observed. Substance-related effects however were obvious with regard to egg production, fertility, hatching success, and survival of 14 day-old chicks. A clear dose dependency was given regarding effects on egg weight and on hatchability. The no-observed-effect concentrations for these two parameters was 60 mg/kg TBTO, characterizing these parameters as the most sensitive in this investigation. With the presented set of test parameters further aspects of subchronic toxicity in adults and chicks can be assessed as well as the validity of the performed test. Comparing the results for most test parameters consistency is obvious, thus confirming the applicability of the presented test guideline. PMID- 8507100 TI - Biochemical and toxicological studies on the mixtures of three commonly-used herbicides in mice. AB - Herbicidal-mixtures have not been adequately studied in biological systems. Therefore, mixtures of three commonly-used herbicides were evaluated. Alachlor (AL), atrazine (AT), picloram (PI), AL+AT, AT+PI, PI+AL and AL+AT+PI, at 10 ppm (in drinking water) of each herbicide, were provided to mice for 30, as well as for 90, days ad libitum; these herbicides and mixtures, at 100 mg/kg (in corn oil) of each herbicide, were also given to additional groups of mice by oral intubation daily for 21 days. In the 30-day test, the spleen/body weight ratios on Day 31 with respect to the control were increased in the AT (53%) and AL+AT (44%) groups. Decreases in the body weights were noted in the treated groups after Day 31 during the 90-day test. Serum glutamic-pyruvic transaminase (SGPT), glutamic-oxalacetic transaminase (SGOT) and alkaline phosphatase activities with AL+AT+PI were elevated by 36-92% on Day 91; SGPT (34%) and SGOT (73%) activities were increased with AL. During the 21-day oral intubation study, the mouse body weights in the mixture groups were generally lower than the control (p < or = 0.05). The liver/body weight ratios were elevated in all groups (16-38%); the spleen/body weight ratio increased with PI (50%). The kidney/body weight ratios were high with PI+AL and AL+AT+PI (p < or = 0.05). Excluding AT, the pentobarbital-induced sleep was less (51-77%) in the herbicide-treated groups. Also, necrosis of individual and small groups of hepatocytes was noted with the mixtures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507101 TI - Comparison of the cytotoxicities of Fusarium metabolites and Alternaria metabolite AAL-toxin to cultured mammalian cell lines. AB - Four water-soluble Fusarium metabolites (fumonisin B1, fusaric acid, butenolide and moniliformin), water-insoluble pigment (8-O-methylbostrycoidin), and an Alternaria metabolite (AAL-toxin) were tested for relative cytotoxicity to five established mammalian cell lines. Butenolide was the most cytotoxic to all five cell lines. LC50s were; 1 microgram/ml to rat hepatoma (RH) (tumors derived from parenchymal cells), 7 micrograms/ml to baby hamster kidney (BHK-21) fibroblast cells, and 15 micrograms/ml to McCoy mouse (MM) fibroblast cells: LC100s were 1 microgram/ml to Chinese hamster ovary (CHO) fibroblast cells, and 5 micrograms/ml to dog kidney (MDCK) fibroblast cells. Fusaric acid was cytotoxic to the MDCK, MM, RH, and CHO cell lines; moniliformin was cytotoxic to the RH, CHO, and MDCK, cell lines. The pigment, however, was cytotoxic only to RH and CHO cell lines. Fumonisin B1 and a related toxin, AAL-toxin, at a high dose level (100 micrograms/ml) were not cytotoxic to the RH, BHK, MM, CHO and MDCK cell lines. T 2 toxin was used as a positive control, and inhibited all cell lines at the nanogram level. The difference in response of these five cell lines to the toxic metabolites, that were noted in this study, was then used to evaluate nine HPLC fractions obtained from a methanol-water extract of an F. moniliforme culture. The results indicated that this type of cytotoxicity assay may be useful in following the isolation of metabolites from extracts of Fusarium culture, especially F. moniliforme. PMID- 8507102 TI - The prevalence and retention of lead pellets in Japanese quail. AB - Thirty-six Japanese quail (18 control birds, 18 lead-dosed birds) were used. The 18 quail were dosed with #4 lead weight that were orally inserted into the proventriculus. Delta-aminolevulunic acid dehydrase (ALAD) activity in erythrocytes in the dosed quail decreased 90% (p < 0.01) after one week as compared with the undosed quail. This inhibition of ALAD activity in erythrocytes indicates lead exposure. Radiographics were obtained at 0, 1, 4, 9, 22, and 32 days. The lead pellets remained in the gizzard and became smaller in 4 days. At day 22, after the lead treatment, in 8 quail of the treated quail 12, the lead pellets disappeared. At day 32, all lead pellets disappeared. These findings indicate that the ingested lead pellets are absorbed gradually in the intestine. The lead concentrations in the blood, liver, kidney, and femur of the lead-dosed quail were significantly higher than in the undosed quail until the 6th week. At week 2, the lead concentration of the proventriculus, gizzard, gizzard contents, duodenum, small intestine, and cecum in the dosed quail was significantly higher. Lead concentration of feces was significantly higher at weeks 2 and 4 (p < 0.01). Throughout this study, no lead pellets were found in the feces. PMID- 8507103 TI - Effects of paraquat on Mg(2+)-ATPase activity in rat liver. AB - Intraperitoneal injection of paraquat (70 mg/kg) elicited a significant decrease of 20% in activity of Mg(2+)-ATPase in hepatic mitochondria, which is always surrounded by a high concentration of oxygen, in rats. The decrease of mitochondrial Mg(2+)-ATPase activity was completely abolished by pretreatment with vitamin E, which is a scavenger of oxygen radicals. On the other hand, paraquat administration did not change the Mg(2+)-ATPase activity in endoplasmic reticulum, which exists in an anaerobic condition in living cells. When liver microsomes were incubated with 1 mM paraquat under aerobic conditions, the Mg(2+) ATPase activity was decreased by 42%. The decrease of Mg(2+)-ATPase activity was completely eliminated by pretreatment with vitamin E. Furthermore, lipid peroxidation in microsomes was tremendously increased by the addition of 1 mM paraquat under aerobic conditions. The increase of lipid peroxidation was completely abolished by preadministration of vitamin E in rats. The results suggest that the inhibition of Mg(2+)-ATPase activity induced by paraquat may be mediated by active oxygen, which is produced by the reaction of paraquat radicals; molecular oxygen may be involved in the induction of hepatic cell injury. PMID- 8507104 TI - Micronucleus incidence and hematological effects in bullfrog tadpoles (Rana catesbeiana) exposed to 2-acetylaminofluorene and 2-aminofluorene. AB - The micronucleus technique used with Rana catesbeiana tadpoles is useful for the evaluation of aromatic amine toxicity. When exposed to increasing concentrations of the aromatic amine 2-acetylaminofluorene (2-AAF 1 x 10(-8) M to 5 x 10(-5) M), R. catesbeiana tadpoles responded with an increasing frequency of micronuclei (MN) in the peripheral blood. Micronuclei increased fourfold with the 5 x 10(-5) M 2-AAF exposure. Micronuclei frequency significantly increased with concentrations as low as 5 x 10(-8) M. The time from initial mutagen exposure to the time of maximum number of MN present in the peripheral blood occurred at two separate times: 2 d and 14 d after exposure. The occurrence of two MN frequency peaks may be due to the presence of two erythrocyte populations from two hemopoietic sources (liver and kidneys) in young tadpoles. The occurrence of immature erythrocytes, as well as general degenerative changes [such as fragmentation (schistocytosis)] in the erythrocytes and vacuolated cytoplasms suggested 2-AAF may contribute to hemolytic anemia effects. 2-AAF also increased the frequency of rubricytes found in the peripheral blood, but had no significant effect on the hematocrit values of animals exposed to concentrations up to 1 x 10(-5) M. The tadpoles may have been producing rubricytes to replace the damaged red blood cells (RBCs). The direct-acting mutagen 2-aminofluorene (2-AF) was considerably more toxic to peripheral RBCs than the indirect-acting 2 AAF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507105 TI - Bone-lead analysis: development of analytical methodology for milligram samples. AB - A graphite platform-in-furnace atomic absorption spectrometric (GFAAS) method for determining micrograms/g levels of Pb in 10-20 mg cortical and trabecular primate bone samples is described. The GFAAS method is based on an ambient temperature nitric acid digestion of the sample, matrix modification with palladium nitrate, stabilized temperature platform furnace atomization, and a systematic evaluation of the temperature program of the atomizer. The method of standard additions is mandatory. The detection limit (3 standard deviations of the blank) is 0.19 micrograms Pb/g dry weight for a 10-mg sample taken up in a 1-mL volume. Data are presented on the degree of accuracy and precision. The accuracy of the proposed GFAAS method has been assessed using the IAEA bone reference material, H-5, and by comparing the values obtained in a bone sample with an isotope dilution mass spectrometric (IDMS) procedure. The GFAAS method can be applied to the determination of Pb in 10-20 mg bone samples and for concentrations which are > or = 10 x detection limit. The method is simple, fast, and contamination-free since the entire operation from weighing to GFAAS measurement is carried out in the same centrifuge tube. The method has been applied to the determination of total-Pb in some adult and fetal primate cortical and trabecular bone specimens. PMID- 8507106 TI - Determination of polycyclic aromatic hydrocarbons in the lung. AB - Polycyclic aromatic hydrocarbons (PAHs) accumulated in human lung samples from men (n = 236) and women (n = 128) were determined by high-performance liquid chromatography (HPLC) to examine their association with lung cancer. The mean values for benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), and benzo[g,h,i]perylene (BghiP) in lungs (ng/g dry lung) of Japanese autopsied patients were 0.54, 0.44, and 0.87, respectively. The modal values were 0.3, 0.3 and 0.5, respectively. Each of the PAH concentrations was highly correlated with the others (r > 0.83). PAH concentrations in the lungs showed age-related increases with low correlation-coefficient values. BaP, BkF and BghiP concentrations in lungs of various subgroups were in the following order: male > female; and lung cancer > all cancers > non-cancer among male not female group. Only BghiP concentration in the lungs of the male smoker group is significantly higher (P < 0.10) than that of the male non-smoker group. Even among non-smoker groups, PAH concentrations in the lungs of male group were significantly higher than those of female group. In the male population, excess exposure to PAHs together with fine carbon particles, such as tobacco smoke or diesel exhaust, correlated with increased prevalence of lung cancer. PMID- 8507108 TI - The effect of synthetic dermal secretion on transfer and dissipation of the insecticide aldicarb from granular formulation to fabric. AB - This research investigated the potential for contamination of fabric by aldicarb (Temik 15) pesticide. Fabric soiled with synthetic perspiration or synthetic sebum was contaminated with Temik granules for various time periods and extracted with methanol. Extracts were analyzed with high performance liquid chromatography. The aldicarb transferred to both soiled and unsoiled fabric; however, the sebum soil and longer contact time increased the transfer of aldicarb to fabric. The dissipation of aldicarb from fabric was affected by the soil type and the formulation of the Temik granule. It is apparent a potential for dermal exposure to granular pesticide exists when the pesticide is trapped in pockets or folds of clothing. PMID- 8507107 TI - Elimination of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) from human blood in the Yusho and Yu-Cheng rice oil poisonings. AB - The pharmacokinetics of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in humans was studied by monitoring the blood concentrations of individuals who ingested a contaminated rice oil in Japan (yusho) in 1968 and in Taiwan (yu-cheng) in 1979. Sixteen yusho patients were followed from 1982 to 1990 and three yu-cheng individuals from 1980 to 1989. From the three yu-cheng patients, blood lipid values for the two persistent toxic congeners, 2,3,4,7,8 pentachlorodibenzofuran (PnCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HxCDF), varied from 50 micrograms/kg at first sampling to about 1 micrograms/kg at last sampling corresponding to half-lives for elimination (t1/2) of 2-21/2 years. The blood lipid values for the same PCDF congeners in yusho patients varied from 5 micrograms/kg down to 0.1 micrograms/kg. The calculated t1/2 were more variable with median values closer to 10 years. Planar PCBs #126 and #169 were present at lower concentrations than the PCDFs. For seven of the other PCB congeners, half lives for elimination in the yu-cheng individuals varied from 1.2 up to 4.6 yr depending on the degree of chlorination. For the yusho patients, the elimination for the PCBs was longer. These results show that clearance of the toxic PCDFs and PCBs in humans is non-linear with faster elimination at higher exposure followed by slower decreases as background levels are approached. Such a clearance pattern can best be explained by a two compartment liver and fat pharmacokinetic model. PMID- 8507109 TI - Effect of total parenteral nutrition on amino acid and glucose transport by the human small intestine. AB - OBJECTIVE: The effect of total parenteral nutrition (TPN) on small intestinal amino acid transport activity was studied in humans. SUMMARY BACKGROUND DATA: Studies in humans receiving TPN indicate that a decrease in the activities of the dissacharidase enzymes occurs, but morphologic changes are minimal with only a slight decrease in villous height. METHODS: Surgical patients were randomized to receive TPN (n = 6) or a regular oral diet (controls, n = 7) for 1 week before abdominal surgery. Ileum (5 controls, 5 TPN) or jejunum (2 controls, 1 TPN) were obtained intraoperatively and brush-border membrane vesicles (BBMV) were prepared by magnesium aggregation/differential centrifugation. Transport of L-MeAlB (a selective system A substrate), L-glutamine, L-alanine, L-arginine, L-leucine, and D-glucose was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. RESULTS: Vesicles demonstrated approximately 18-fold enrichments of enzyme markers, classic overshoots, transport into an osmotically active space, and similar 1-hour equilibrium values. TPN resulted in a 26-44% decrease in the carrier-mediated transport velocity of all substrates except glutamine across ileal BBMVs. In the one patient receiving TPN from whom jejunum was obtained, there was also a generalized decrease in nutrient transport, although glutamine was least affected. Kinetic studies of the system A transporter demonstrated that the decrease in uptake was secondary to a reduction in carrier Vmax, consistent with a decrease in the number of functional carriers in the brush-border membrane. CONCLUSIONS: TPN results in a decrease in brush border amino acid and glucose transport activity. The observation that glutamine transport is not downregulated by 1 week of bowel rest may further emphasize the important metabolic role that glutamine plays as a gut fuel and in the body's response to catabolic stresses. PMID- 8507110 TI - Serum transferrin as a prognostic indicator of spontaneous closure and mortality in gastrointestinal cutaneous fistulas. AB - OBJECTIVE: This study determined whether there are any laboratory or other features that will enable prediction of spontaneous closure in patients with gastrointestinal cutaneous fistulas. SUMMARY BACKGROUND DATA: Although the anatomic criteria for spontaneous closure of gastrointestinal cutaneous fistulas have been presented by several authors, less than 50% of such fistulas tend to close, even in the most recent series. METHODS: A group of patients with gastrointestinal cutaneous fistulas with anatomical features favorable to study were investigated with respect to a series of parameters including the usual demographic parameters, plus fistula output, number of blood transfusions, presence of sepsis, as well as metabolic parameters including serum transferrin, retinol-binding protein, thyroxin-binding prealbumin, and serum albumin. RESULTS: Of 79 patients with 116 fistulas, 16 (20.3%) died. Causes of death were uncontrolled sepsis in eight patients and cancer in five patients. Postoperative fistulas constituted 80% of the group. The presence of local sepsis, systemic sepsis, remote sepsis (such as pneumonia or line sepsis), the number of fistulas, fistula output, and the number of blood transfusions were not predictive of spontaneous closure, whereas serum transferrin was predictive of spontaneous closure. Serum transferrin, retinol-binding protein, and thyroxin-binding prealbumin were predictive of mortality. CONCLUSIONS: Serum transferrin does not appear to be an entirely independent variable, but seems to identify those patients with significant remote sepsis, systemic sepsis, and neoplasia in whom these processes are clinically significant. The results, if confirmed, and provided that nutritional needs are met, suggest that short-turnover proteins, particularly serum transferrin, might be useful in predicting which patients with gastrointestinal cutaneous fistulas should undergo surgery despite anatomic criteria favorable for spontaneous closure. PMID- 8507111 TI - Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide. AB - OBJECTIVE: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega Nitro-L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. RESULTS: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine. Treatment with NNA reversed the beneficial effects of arginine on immune defense. CONCLUSIONS: The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway. PMID- 8507112 TI - Tumor necrosis factor-induced mortality is reversed with cyclooxygenase inhibition. AB - OBJECTIVE: The authors hypothesized that TNF would induce eicosanoid synthesis, and a cyclooxygenase inhibitor would attenuate both eicosanoid synthesis and improve survival in an LD90 TNF-induced (150 ng/kg/i.v./5 min) mortality model. SUMMARY BACKGROUND DATA: Tumor necrosis factor is a cardinal mediator in sepsis; however, little is known about its effects on arachidonate metabolism. METHODS: Conscious male rats with carotid arterial and jugular venous catheters were randomized for mortality: group I, TNF alone (150 kg/i.v./15 min, n = 30); group II, ibuprofen (30 mg/kg/i.v. at t = -20 and +240 min), plus TNF, (n = 28); and for hemodynamics, eicosanoid synthesis, blood gases: group III, TNF alone, (n = 8); group IV, ibuprofen + TNF (n = 8); group V, monoclonal antibody to TNF plus TNF (n = 8). Mortality was determined at 4-72 hr. Other parameters determined over 4 hours (0, 5, 60, 120, 240 min). RESULTS: TNF stimulated synthesis of (a) TXB2 (71 +/- 30 pg/ml, mean +/- SE at base vs. 117 +/- 18 at 4 hr, p < 0.02); (b) PGE2 (70 +/- 6 pg/ml at base vs. 231 +/- 68 at 4 hr, p < 0.02); (c) 6PGF (52 +/- 6 pg/ml at base vs. 250 +/- 80 at 4 hr, p < 0.02). Ibuprofen significantly (p < 0.05) inhibited eicosanoid synthesis from TNF. TNF-induced mortality (87%, 26/30) was dramatically decreased with ibuprofen (11%, 3/28), at 4, 24, and 72 hr (p < 0.01). Monoclonal antibody to TNF prevented all abnormalities and had 100% survival. Hemodynamic events were similar in both groups, but metabolic acidosis was attenuated with ibuprofen. CONCLUSIONS: TNF stimulates arachidonic acid metabolism in vivo. A cyclooxygenase inhibitor attenuates eicosanoid synthesis and dramatically improves survival. TNF appears to have different effect on tissues that synthesize certain eicosanoids. Hypotension from TNF is not mediated via the eicosanoids. TNF-induced mortality, like endotoxemia/sepsis may be mediated, in part, via arachidonic acid metabolites. These new findings support the notion that cyclooxygenase inhibitors may be used as adjunctive therapy in clinical sepsis. PMID- 8507113 TI - Barrett's esophagus in children. Diagnosis and management. AB - OBJECTIVE: To determine the local prevalence and optimal therapy for children with Barrett's esophagus (BE), the authors studied children with esophageal strictures or gastroesophageal reflux (GER), or both, to diagnose BE and to follow after therapy. SUMMARY BACKGROUND DATA: Barrett's esophagus is seldom reported in children and therapeutic recommendations are unclear. Barrett's esophagus usually develops during the mucosal reparative process after acid reflux injury to the esophageal mucosa. Risk factors for BE include conditions that are associated with GER such as mental retardation, esophageal stricture, esophageal atresia, and reversed gastric tube esophagoplasty. Barrett's syndrome increases the risk of esophageal adenocarcinoma by 30 to 40 times. METHODS: All children with the risk factors had repeated esophagoscopy and multiple mucosal biopsies before and after therapy. RESULTS: Eleven children have been documented with BE. The initial diagnoses were: GER, 5; esophageal atresia, 4; nasogastric intubation, 1; lye ingestion, 1. A gastric tube esophagoplasty had been performed in three patients with BE in the esophagus proximal to the anastomosis. Three children with mid-esophageal strictures and long segments of BE had total resection with colic interposition. An additional two patients with tight stricture were treated with colic-patch esophagoplasty without resection. The final three patients were treated with fundoplication alone. CONCLUSIONS: Barrett's esophagus can be caused by acid from gastric tubes but responds to H2 blockers and diet. Resection eliminates BE; esophagoplasty only controls the stricture and must be accompanied by fundoplication. Barrett's esophagus persists in patients with fundoplication alone if reflux control is incomplete. The authors conclude that acid reflux must be controlled to treat BE successfully or the involved segment must be resected. Esophagogastrostomy apparently predisposes to BE. PMID- 8507114 TI - Impact of completion angiography on operative conduct and results of carotid endarterectomy. AB - OBJECTIVE: This study assessed the impact of operative completion angiography on conduct and results of carotid endarterectomy (CEA). SUMMARY BACKGROUND DATA: Completion imaging by angiography, ultrasound or angioscopy reveals occasional residual lesions after CEA. The importance and appropriate management of these lesions remain controversial with respect to operative morbidity and long-term restenosis. METHODS: Carotid endarterectomy was performed 410 times for transient ischemic attack (44%), amaurosis fugax (19%), prior stroke (10%), and asymptomatic carotid stenosis (27%). Routine intraoperative completion angiograms were obtained to exclude significant residual lesions. Postoperative ultrasound follow-up was obtained in 232 patients over a mean interval of 17.3 months. RESULTS: Angiography revealed 71 defects warranting correction in 66 cases (16.1%), including kinks (23), external carotid flaps (18), common carotid plaque (10), thrombus (10), distal internal carotid stenosis (8), intracranial occlusion (1), and spasm (1). Operative morbidity included seven ipsilateral strokes (1.7%) and operative mortality was 0.7%. During follow-up, restenosis > 80% was detected in 17 (7.3%) of 232 arteries, 9 (3.9%) of which underwent reoperation. Rates of restenosis of > 80% were similar between sexes and patched versus unpatched arteries. CONCLUSIONS: Routine completion angiography after CEA guides use of selective operative revision contributing to low rates of perioperative morbidity and restenosis. PMID- 8507115 TI - Carbon dioxide gas as an arterial contrast agent. AB - OBJECTIVE: To investigate the clinical utility of CO2 gas as an arterial contrast agent, the experience with CO2 arteriography at the University of Florida was reviewed. SUMMARY BACKGROUND DATA: Preliminary studies have demonstrated the feasibility of CO2 arteriography and shown that arterial injection of CO2 gas appears non-toxic (which could limit the risks of contrast induced renal injury and allergic reaction). However, numerous technical problems make CO2 arteriography a demanding technique and recent studies have suggested that distal lower extremity vessels are difficult to image using CO2 arteriography, especially when significant arterial occlusive disease is present. METHODS: One hundred twenty-eight CO2 arteriograms done in 115 patients were reviewed. CO2 arteriograms were graded as excellent, good, poor, or inadequate by two blinded observers and results of CO2 studies compared to results of standard contrast studies (done in 98 patients for image comparison). In addition, a therapeutic plan based on the CO2 arteriograms was compared with the therapy each patient received. RESULTS: One hundred-seventeen (91%) of the CO2 arteriograms were of good or excellent quality and agreement between CO2 studies and standard contrast studies was seen in 93 of 98 cases (95%). Accurate therapeutic plans based on CO2 studies were possible in 92% of cases with inadequate visualization of infrapopliteal arteries being the major limitation (7 cases). No allergic reactions occurred and only one patient potentially had contrast-induced nephrotoxicity. CONCLUSIONS: CO2 arteriography provides accurate, clinically useful arterial imaging with minimal risk. Thus, this new technology significantly increases the utility of arteriography in patients with peripheral vascular disease. PMID- 8507116 TI - Arterial reconstruction of vessels in the foot and ankle. AB - OBJECTIVE: This study demonstrated that arterial reconstruction of vessels of the foot and ankle can preserve the majority of ischemic extremities with extensive tibial and peroneal occlusive disease and patent pedal arteries. SUMMARY BACKGROUND DATA: There are successful reports of bypass procedures to the ankle and foot, but despite this, these procedures have not gained widespread acceptance among surgeons performing infra-inguinal revascularization. Primary amputation is often offered for such patients. For this reason, the authors have reviewed their experience with bypasses to the foot and ankle. METHODS: A retrospective review was done of 75 arterial bypasses (5 bilateral), done since 1985, to the ankle and foot in 70 patients (38 males and 32 females). Fifty-four (77%) of the patients were diabetic. The age ranged from 55 to 95 years. Twenty six (37%) were older than 80 years. The patients were selected for operative intervention because of severe tibioperoneal occlusive disease with ischemic rest pain or gangrene of the foot. Digital subtraction arteriography facilitated visualization of distal vessels. Operative principles included regional anesthesia, autogenous graft material, short bypass, non-traumatic vessel occlusion, selective operative arteriography, tension free ankle and foot skin closure, and concomitant conservative debridement of infected devitalized tissue. Incomplete pedal arch did not influence decision for operation. Indications for operation were: gangrene, 42 (56%); non-healing ulcer, 21 (28%); and rest pain, 12 (16%). Graft material was in situ greater saphenous vein, 40 (53%); translocated greater saphenous vein, 19 (25%); reversed greater saphenous vein, 11 (15%); and arm vein, lesser saphenous vein or vein patch, 5 (7%). Donor artery was popliteal, 30 (41%); common femoral, 26 (35%); and superficial femoral, 17 (23%). Recipient vessel was dorsalis pedis, 43 (57%); posterior tibial, 18 (24%); distal anterior tibial, 9 (12%); and distal peroneal, plantar or tibial endarterectomy, 5 (7%). RESULTS: There were four (5.7%) deaths and three (4.2%) graft failures within 30 days. Early graft failure led to transmetatarsal amputation (1), below knee amputation (1), and conversion of graft to femoral (1), popliteal bypass graft with limb salvage (1). In one patient, significant tissue necrosis with infection necessitated a below knee amputation within 30 days, despite a patent graft. Long-term follow-up revealed 10 graft failures, 4 major amputations, 3 graft revisions, and 15 deaths. Cumulative primary and secondary patency was 79.0% and 81.6% at 36 months. Limb salvage was 87.5% at 36 months. CONCLUSIONS: These results support an aggressive approach to limb salvage in patients with threatened limb loss, unreconstructable tibio-peroneal occlusive disease, and patent pedal arteries. Bypasses to the ankle and foot will maintain a functional extremity in the majority of these patients. PMID- 8507117 TI - Long-term fate of the aortic root and aortic valve after ascending aneurysm surgery. AB - OBJECTIVE: The authors determined in which patients tube graft replacement could be used. SUMMARY BACKGROUND DATA: Tube graft replacement of ascending aortic aneurysms requires no coronary anastomoses and preserves the native aortic valve, but aortic insufficiency or aortic root aneurysms may develop requiring reoperation. Use of Bentall or Cabrol composite valve graft procedures obviates these problems but requires prosthetic valve replacement and coronary reattachment, both of which are associated with complications. These two procedures have been applied increasingly but because of renewed interest in aortic valve preservation and reconstruction, the authors determined in which patients tube replacement could be used. METHODS: The authors analyzed the fate of 277 patients, mean age 49 +/- 14 years, operated on between 1953 and 1992 by techniques that preserved the aortic root. The most common pathology was atherosclerosis in 104 patients. Perioperative mortality since 1975 was 14%. RESULTS: Fifteen patients required reoperation on the ascending aorta or aortic root; ascending aneurysm reoperation (6 patients); aortic valve replacement (8 patients), and a combined procedure (1 patient). Of these 15 patients, 8 had Marfan's syndrome, 10 had dissections, and 5 had medial degeneration/necrosis. CONCLUSIONS: Simple tube graft replacement of the ascending aorta was a durable technique in patients without Marfan's syndrome or medial degeneration/necrosis and allowed preservation of the native aortic valve in many patients. PMID- 8507118 TI - Operative treatment of abdominal aortic aneurysms in octogenarians. When is it too much too late? AB - OBJECTIVE: This study evaluated the value of operation for treatment of all octogenarians with ruptured abdominal aortic aneurysms (AAA). SUMMARY BACKGROUND DATA: Elective AAA resection in octogenarians is safe, with published operative mortality rates of approximately 5%. Published operative mortality rates of ruptured AAA in this age group, however, vary from 27 to 92%. METHODS: To evaluate this question, we extracted the clinical course of the 34 octogenarians submitted to AAA resection by the authors from our total experience of 548 resections performed during the past 7 1/2 years. In this subgroup of octogenarians, 18 underwent elective AAA replacement, 5 were submitted to urgent resection of active but intact AAAs, and 11 had operations for ruptured AAAs. There were 23 males and 11 females in the group. The ages ranged from 80 to 91 years. RESULTS: Operative mortality in the patients managed electively was 5.6%. Two of the five patients (40%) submitted to operation for active yet unruptured aneurysms died in the preoperative period. Finally, 10 of the 11 patients (91%) with ruptured AAAs were operative mortalities. All of these operative mortalities in the ruptured AAA subgroup had severe hypotension preoperatively (mean systolic blood pressure: 23 mm Hg). The charges associated with the management of the ruptured AAA group averaged $84,486 (range $12,537-$199,233). CONCLUSIONS: Although elective replacement of AAA in properly selected octogenarians appears valuable to prolong worthwhile life expectancy, this experience leads us to consider observation only in the treatment of octogenarians with ruptured AAA who present with severe hemodynamic instability. PMID- 8507119 TI - Management of abdominal aortic graft complications. AB - OBJECTIVE: This study reviews the outcome of 61 patients who underwent 66 reoperations for complications of aortic grafts. There were 25 patients with false aneurysm of an aortic anastomosis and 41 patients with graft infection, 17 of whom had involvement of the gastrointestinal tract. SUMMARY BACKGROUND DATA: Significant late complications of aortic grafting occurred in 2% of patients. The mode of clinical presentation, the clinical characteristics, and outcome in these patients has not been emphasized. METHODS: This study reviews our experience with patients with complications of aortic grafts requiring graft excision or replacement with a view towards identifying prominent and important clinical characteristics and predictors of successful treatment. CONCLUSIONS: Patients with involvement of the gastrointestinal tract have higher mortality and morbidity than patients with simple aortic graft infection or those who require aortic graft replacement for pseudoaneurysm formation at the aortic anastomosis. These patients require longer hospitalization, more blood transfusion, and have higher operative and long-term mortality. Revascularization of the lower extremities should be attempted and has a high rate of limb salvage although revision or thrombectomy may be required. The authors recommend complete graft excision and extra-anatomic bypass for patients with aortic graft infections. PMID- 8507120 TI - Failure of 'predictors' of cardiopulmonary resuscitation outcomes to predict cardiopulmonary resuscitation outcomes. Implications for do-not-resuscitate policy and advance directives. PMID- 8507121 TI - Infections due to penicillin-resistant pneumococci. Clinical, epidemiologic, and microbiologic features. AB - Pneumococcal infection remains a common cause of serious morbidity and mortality throughout the world. Until recently, clinical isolates of pneumococci that were penicillin resistant were rare. However, 4% to 5% of the clinical isolates in the United States were recently found to be either intermediately resistant or highly resistant to penicillin. Clinicians in every field of medicine must therefore be better informed regarding penicillin-resistant pneumococcal infections to minimize their attendant morbidity and mortality and increase compliance with preventive measures. We reviewed the molecular, genetic, and epidemiologic aspects of penicillin-resistant pneumococcal infections, with emphasis on their microbiologic and clinical features. PMID- 8507122 TI - Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. AB - BACKGROUND: Treatment of severe hypercholesterolemia often requires high-dose therapy with a hydroxymethylglutaryl-coenzyme A reductase inhibitor alone or in combination with bile acid-binding resin. We evaluated the efficacy and safety of pravastatin, a new hydroxymethylglutaryl-coenzyme A reductase inhibitor with hydrophilic selectivity, alone and in combination with cholestyramine. METHODS: Pravastatin was studied at doses of 20 or 40 mg twice daily alone or 20 mg twice daily with cholestyramine, 12 g twice daily, vs placebo in a randomized, double blind multicenter study of 311 patients for 8 weeks and in continued therapy through 24 weeks. RESULTS: After 8 weeks of therapy, pravastatin in a dosage of 20 mg twice daily reduced low-density lipoprotein cholesterol levels by 31%, whereas a dosage of 40 mg twice daily reduced low-density lipoprotein cholesterol levels by 38%. Cholestyramine, 24 g daily alone, reduced low-density lipoprotein cholesterol levels by 32%. Cholestyramine combined with 40 mg of pravastatin reduced the level by 51%. Pravastatin, 40 or 80 mg daily, reduced the triglyceride level by 13% to 19%, resin alone increased the triglyceride level by 21%, and no change was seen with combined therapy. High-density lipoprotein cholesterol levels increased by about 5% regardless of regimen. Similar effects were seen at 24 weeks. Symptoms reported were indistinguishable among placebo and pravastatin users and were less than with cholestyramine alone or cholestyramine in combination with pravastatin. Elevations of liver enzyme levels were small in all groups, indistinguishable between resin and pravastatin, and were highest when the two drugs were combined. Plasma creatine kinase levels did not increase in any treatment group. CONCLUSIONS: Pravastatin treatment of hypercholesterolemia is highly effective and well tolerated alone and in combination with bile acid-binding resin and shows no tendency to increase muscle enzyme levels. PMID- 8507123 TI - Safety of nonsteroidal anti-inflammatory drugs with respect to acute liver disease. AB - OBJECTIVE: To examine the magnitude of the risk of acute hepatitis associated with the use of nonsteroidal antiinflammatory drugs. METHODS: We calculated the annual incidence rate of hepatitis resulting in hospitalization and then performed a case-control study using 1980 to 1987 Medicaid billing data from Michigan and Florida. The 107 cases included patients with symptomatic acute hepatitis without an identifiable cause of liver disease. Four controls per case were randomly selected and were matched for age, sex, and state. Antecedent drug exposure was assessed 30 days prior to the onset of the disease in the cases and during the same period in the controls. RESULTS: The annual incidence rate (95% confidence interval) of acute idiopathic symptomatic hepatitis resulting in hospitalization was 2.2 (2.0 to 2.4) per 100,000 persons per year. Nine cases (8.4%) and 26 controls (6.1%) were exposed to nonsteroidal anti-inflammatory drugs, yielding an odds ratio of 1.4 (0.6 to 3.1). After adjustment for potential confounding variables, the odds ratio was 1.2 (0.5 to 2.8). CONCLUSIONS: Acute symptomatic idiopathic liver disease severe enough to result in hospitalization is uncommon, and no association was evident between nonsteroidal anti inflammatory drugs and acute hepatitis. This study was large enough to exclude a relative risk of 2.8. These data suggest that acute symptomatic liver disease from nonsteroidal anti-inflammatory drugs is not a frequent clinical problem. PMID- 8507124 TI - Assessing the clinical importance of symptomatic improvements. An illustration in rheumatology. AB - OBJECTIVE: To estimate when a difference in disability symptoms is sufficiently large to be important to individual patients. DESIGN: Cross-sectional analysis of two groups: derivation set (n = 46) and validation set (n = 57). SETTING: The Arthritis Foundation, Northern California Chapters. PARTICIPANTS: Volunteer sample of patients with arthritis who live in the community. MAIN OUTCOME MEASURES: We applied the Stanford Health Assessment Questionnaire to assess the functional status of individuals. Participants then conducted one-on-one conversations with each other and rated whether their disability was "much better" "somewhat better," "about the same," "somewhat worse," or "much worse" relative to each person they met. For every conversation we calculated the difference between the two participants' health assessment questionnaire scores and linked the difference to the subjective comparison ratings of each individual in the pair. RESULTS: Health assessment questionnaire score differences were significantly correlated with subjective comparison ratings (correlation coefficient, .41; 95% confidence interval, 0.31 to 0.50). We estimated that health assessment questionnaire scores needed to differ by about 0.19 units for average respondents to stop rating themselves as "about the same" and start rating themselves as "somewhat better" (95% confidence interval, 0.10 to 0.28). Analysis of a second group of patients revealed a similar threshold (mean, 0.23 units; 95% confidence interval, 0.13 to 0.23). In both groups, health assessment questionnaire score differences were imperfect predictors of individual ratings and the threshold for less disabled participants tended to be lower than the threshold for more disabled participants. CONCLUSIONS: Some statistically significant differences in functional status scores may be so small that they represent trivial degrees of symptom relief. An awareness of the smallest difference in symptom scores that is important to patients can provide a rough guide to help clinicians interpret the medical literature. PMID- 8507125 TI - High-molecular-weight hydroxypropylmethylcellulose. A cholesterol-lowering agent. AB - BACKGROUND: We assessed the efficacy of a high-molecular-weight hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent, the dose response profile of its action, and the ability of adult subjects to tolerate its ingestion at effective doses. METHODS: These studies were conducted at the Clinical Research Center of The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed in 10 normal and 12 mildly hyperlipidemic subjects in double-blind, randomized crossover trials of 1 and 2 weeks' duration, respectively. The dose-response profile was studied in 12 mildly hypercholesterolemic subjects in a nonrandomized control trial with doses given in escalating order. Tolerance was assessed by a questionnaire of adverse effects and bowel movement habits in all subjects. RESULTS: We found that 10 g of K8515 ingested in a prehydrated form three times a day with meals lowered total cholesterol levels by an average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1 week. In two studies in subjects with mildly elevated cholesterol levels (with entry levels ranging from 5.35 mmol/L [207 mg/dL] to 6.70 mmol/L [260 mg/dL]), average reductions of 1.00 mmol/L (39 mg/dL) (18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same period. The effect was primarily due to a reduction in low-density lipoprotein cholesterol levels. Low density lipoprotein levels in normal subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a week of 10 g of K8515 three times a day with meals, and in the two studies in subjects with mild hyperlipidemia, the reductions in low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL) (23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency for high-density lipoprotein cholesterol levels to decrease, this was significant only in normal subjects. Decreases in cholesterol levels were not accompanied by any rise in triglyceride levels. Dose-response studies in those with mildly elevated cholesterol levels indicated that it is possible to achieve a 15% decrease in low density lipoprotein cholesterol levels within 1 week at a dose of 6.7 g three times a day, with minimal adverse effects. CONCLUSION: These results suggest a role for high-molecular-weight hydroxypropylmethylcellulose in the clinical treatment of mild hypercholesterolemia. PMID- 8507126 TI - The health care status of the diabetic population as reflected by physician claims to a major insurer. AB - BACKGROUND: Conventional epidemiologic data suggest that diabetic patients use more health care resources than nondiabetic patients, yet overall health care use by diabetic individuals has never been fully quantitated. We took a new approach to this issue based on the actual economics of the provision of health care to diabetic insured individuals. METHODS: The claims records in the Mutual of Omaha Current Trends database, which contains information on more than 400,000 individuals, were surveyed to identify patients with diabetes and create the contrast population of nondiabetic patients by exclusion. International Classification of Diseases, Ninth Revision, Clinical Modification, codes and Physicians' Current Procedural Terminology, Fourth Edition, codes were used to determine all diagnoses recorded and all physician services rendered to the contrast populations. Age- and sex-adjusted comparisons were performed using Mantel-Haenszel procedures to determine an adjusted odds ratio (AOR). RESULTS: A total of 13,304 diabetic individuals and 388,053 nondiabetic individuals who received health care services from January 1, 1988, to January 1, 1989, were identified. Diabetic insured individuals constituted 3.1% of the overall insured population yet accounted for 8.3% of the charges (P < .01). Inpatient charges accounted for 81% of total diabetic charges but only 61.5% of total nondiabetic charges (P < .001). Diabetic insured individuals had twice as many physician office visits (AOR = 1.87; 95% confidence interval [CI], 1.79 to 1.96), with 2.5 times more physician hospital visits [AOR = 2.50; 95% CI, 2.27 to 2.75). However, the increases in physician care were not uniformly distributed across the diagnostic spectrum. The frequencies of well-established complications of diabetes, such as ischemic heart disease (AOR = 3.32; 95% CI, 3.12 to 3.53), peripheral vascular disease (AOR = 3.14; 95% CI, 2.79 to 3.53), and eye disease (AOR = 3.10; 95% CI, 2.94 to 3.27), were threefold higher in the diabetic group, with parallel increases in related medical services, such as cardiac catheterization (AOR = 3.02; 95% CI, 2.27 to 4.0), vascular surgery (AOR = 2.94; 95% CI, 2.64 to 3.27), and ophthalmologic procedures (AOR = 2.94; 95% CI, 2.72 to 3.18). In contrast, most diagnostic categories showed little or no increase. For example, the frequency of neoplasms (AOR = 1.11; 95% CI, 1.03 to 1.19) was minimally increased, and the associated procedural concomitants of therapeutic radiology (AOR = 0.81; 95% CI, 0.47 to 1.39) and chemotherapy (AOR = 0.98; 95% CI, 0.60 to 1.60) were not increased in the diabetic group. CONCLUSIONS: Our most important new finding is that diabetic patients have neither an elevated risk for a wide spectrum of diseases nor an increase in the receipt of physician services for diagnostic categories without increased risk, despite more frequent physician encounters. We provide real-world risk estimates that help in calculating the effect of offering specific insurance to diabetic individuals or including them in group health plans. The techniques we have developed to analyze computerized claims databases in this way may serve to better quantify the true impact of chronic diseases on the health care system. PMID- 8507127 TI - Results of cardiopulmonary resuscitation. Failure to predict survival in two community hospitals. AB - BACKGROUND: The use of closed chest cardiopulmonary resuscitation (CPR) has, since its initial description in 1960, expanded greatly. Recently, much energy has focused on identifying patients' probabilities of responding to CPR. The goal of this study was to determine the current rate of successful CPR in two community teaching hospitals and to identify patient characteristics associated with the likelihood of successful resuscitation. METHODS: A retrospective review of the medical records of all patients receiving CPR during 1988 and 1989 in two university-affiliated teaching hospitals. This review identified 300 patients who experienced in-hospital cardiopulmonary arrest during the study period. RESULTS: Survival of CPR and survival to hospital discharge were 53.9% and 23.3% in the combined populations. Likelihood of survival of CPR was increased when the initial rhythm was ventricular tachycardia or ventricular fibrillation and when the duration of CPR was less than 30 minutes. Survival to hospital discharge was associated with shorter duration of CPR. Combinations of variables did not allow improved prediction of resuscitation results but did aid in predicting survival to hospital discharge. Combinations of variables that were associated with survival in one hospital were not transferable to the other institution. CONCLUSION: Other than the length of resuscitation, easily accessible clinical variables provided limited predictive information about CPR results. PMID- 8507128 TI - Complement factor I deficiency with recurrent aseptic meningitis. AB - Patients with deficiency of the complement regulatory protein factor I typically present with systemic pyogenic bacterial infections, including meningitis. We report a novel case with total deficiency of factor I in serum and plasma; the patient experienced nine consecutive episodes of aseptic meningitis within a 2 year period. There was no history of previous bacterial sepsis. Aseptic meningitis recurred despite attempted penicillin prophylaxis. Each episode resolved rapidly without sequelae, with or without antibiotic treatment. Serum complement profiles showed persistently low levels of C3, factor B, and factor H and undetectable factor I protein. Family complement studies could not be performed. Except for a minimally increased titer of antinuclear antibody, no other immunologic abnormality was detected. Results of an oral ibuprofen challenge were negative. We conclude that deficiency of factor I may predispose to aseptic, as well as pyogenic bacterial, meningitis. PMID- 8507129 TI - Congenital adrenal hyperplasia diagnosed in a man during workup for bilateral adrenal masses. AB - We studied an asymptomatic 55-year-old man who was found to have markedly enlarged adrenal glands on an abdominal computed tomographic scan and was scheduled to have adrenal biopsy because of suspicious findings on an adrenal magnetic resonance image. However, hormonal studies revealed congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Treatment with dexamethasone decreased the size of the adrenal glands. This is, we believe, the first report of congenital adrenal hyperplasia in an adult, diagnosed during the evaluation of an incidental adrenal lesion. Although congenital adrenal hyperplasia can present with varying severity and remain undiagnosed into adulthood, it is usually not considered in the evaluation of asymptomatic adult adrenal masses. We emphasize the need for proper hormonal studies in the evaluation of incidental adrenal lesions. PMID- 8507130 TI - Stevens-Johnson syndrome associated with herpes simplex virus. PMID- 8507131 TI - Tight pants syndrome: a new title for an old problem and often encountered medical problem. PMID- 8507132 TI - [Parental depression and psychopathology of the child]. PMID- 8507133 TI - [Urinary lithiasis after kidney transplantation. Experience at a pediatric center]. AB - BACKGROUND: Urologic complications are still a frequent and significant problem in renal transplant recipients. The search for risk factors is therefore mandatory. MATERIAL AND METHODS: 652 renal transplantations were performed in children and adolescents between January 1973 and December 1988. 33 patients (5%) developed urolithiasis; their files were retrospectively analysed at the same time as the files of 28 patients transplanted during the same period and having similar ages, reasons for transplantation and immunosuppressive therapy. RESULTS: The stones contained calcium in 27 patients and uric acid in 6. The first symptoms were hematuria (27 times) with or without dysuria (9 cases), urine retention (2 cases) and anuria (2 cases). Repeated urine infections frequently led to the use of imaging techniques that permitted diagnosis. Urolithiasis was responsible for urinary obstruction in 13 cases; 9 of these required surgery. The course was always good without any modification of renal functions. The main risk factors were local: ureteral reimplantation on intestinal bladder, use of nonresorbable stitches and repeated urinary infections. Metabolic factors were less frequent and included hypercalciuria (18 cases) and hyperparathyroidism (2 cases). CONCLUSIONS: Some of the risk factors such as urinary infections, changes in the metabolism of phosphorus and calcium or insufficient diuresis, can be prevented. Repeated imaging techniques during the follow-up are mandatory. PMID- 8507134 TI - [Subglottal stenosis following intubation in children]. AB - BACKGROUND: Subglottal stenosis following intubation of children is infrequent, but significant. It is therefore necessary to know more about predisposing factors. MATERIAL AND METHODS: The files of all the 1,006 children who were intubated from 1982 to 1989 were studied. The following data were analysed: weight, height, locality of intubation, type and diameter of tube, reason for intubation, duration of intubation, delay and type of clinical signs of subglottal stenosis, treatment of this complication. RESULTS: Twelve children (1.5%) developed subglottal stenosis; 9 were 5 months to 7 years old; the other 3 were neonates, 2 of them with a very low birth weight. The disease responsible for intubation was neurologic in origin in 6 cases, respiratory in 4 and hemodynamic in 2. The tube used for 4 children was too large, based on standards for age and weight. The mean duration of intubation was 21.1 days (1-129 days). Primary failure to extubate usually revealed subglottal stenosis, which was assessed by laryngoscopy. It was necessary to reinsert a tube for a mean duration of 20.2 days (4-41 days) in 11 of the 12 children; all patients received corticosteroids. 6 children required tracheostomy for 37 to 365 days. Dilation was necessary in 7 children. Finally, 9 children fully recovered, 1 has an asymptomatic persistent stenosis, 1 is still intubated with severe neurologic sequellae and 1 died accidentally, probably as a result of obstruction by tube dilation. CONCLUSION: Stenosis remains a severe complication of intubation. The diameter of the tube is probably the most aggressive factor. It seems preferable to use a smaller, therefore cuffed tube and to secure the airways, if necessary, by inflating the cuff. PMID- 8507135 TI - [Adverse effects of oxybutynin chloride (Ditropan) in pediatrics]. AB - BACKGROUND: The side effects of oxybutynin chloride (Ditropan) often include atropinic and allergic reactions. Their relative frequency in children merits a nationwide investigation. METHODS: All the side effects of Ditropan reported to the French Regional ADR monitoring centers and to the pharmaceutical firm Debat between January 1985 and June 1990 were analysed. Only 87 effects of the 286 side effects reported in adults and children occurred with sufficient frequency in 84 children to warrant study. RESULTS: The 84 children (38 males, 43 females, 3 of unknown sex) were 30 months to 15 years old (mean: 6.5 years); 13 of them were less than 5 years. The mean dose of Ditropan prescribed was 0.5 +/- 0.12 mg/kg/day. 52 children developed atropinic symptoms, 20 skin and/or allergic reactions and 15 various other manifestations. These side effects required admission to hospital in 14% of cases. The side effects were 4 times more frequent in children (1/4,000 regulations) than in adults. CONCLUSIONS: The higher frequency of atropinic reactions in children may be due to the higher dosage of the drug used and/or to differences in hydroxylation metabolism, that is genetically determined in adults. New recommendations for use of this drug are proposed. PMID- 8507136 TI - [Neonatal familial benign convulsions]. AB - BACKGROUND: Some neonatal benign convulsions are genetic in origin, with a dominant mode of inheritance. CASE REPORT: A girl was placed on continuous EEG recording from her 2d day of life because of her family history. The first clonic seizures occurred on the 4th day; they appeared again on the 6th day and became prolonged with an abnormal EEG pattern. The seizures were well controlled with phenobarbital, that was gradually discontinued when the child was 3 months old. Seizures occurred again when she was 4 months old and were again controlled with phenobarbital. Her father had had neonatal convulsions which were not well analysed. Her brother also had clonic seizures at the 4th day of life; they disappeared after 1 month. Her sister suffered from clonic seizures when she was 3 days old, and these became prolonged. She was given phenobarbital until she was 1 year old. She developed benign rolandic epilepsy at the age of 10 years. CONCLUSION: This family suffers from neonatal familial benign convulsions and rolandic epilepsy. The frequency of neonatal familial benign epilepsy is probably under-estimated. PMID- 8507137 TI - [Contribution of nuclear magnetic imaging in the diagnosis of Hallervorden-Spatz syndrome]. AB - BACKGROUND: The manifestations of the Hallervorden-Spatz disease (HSD) usually appear during childhood or in adults. They are not specific and magnetic resonance imaging (MRI) has improved its diagnosis. CASE REPORT: A girl developed progressive motor difficulties, dystony, rigidity, spasticity and mental deterioration, beginning at the age of 18 months. Examination at the age of 13 years showed pigmentary degeneration of the retina and acanthocytosis. The CT scan showed symmetrical calcifications in both globus pallidus. The MRI showed heterogeneity of the globus pallidus, decreased signal intensity of magnetic resonance T2-weighted images with an aspect of "tiger eye". CONCLUSION: The MRI show peculiar signs that may help in the diagnosis of HSD, and eventually in genetic counselling. PMID- 8507138 TI - [Prenatal diagnosis of congenital cerebral tumors. Apropos of 3 cases]. AB - BACKGROUND: The prognosis for congenital brain tumors is usually poor, so that their management during pregnancy is difficult. CASES REPORTS: Case 1. A large cystic mass was revealed by ultrasound at the 37th week of pregnancy; it was located near the brain stem and was associated with ventricular dilation. The newborn was delivered by cesarean section because of an abnormally enlarged head. The CT scan confirmed the presence of this mass containing a fluid that was found to be normal after needle aspiration. Surgical shunting of excess fluid was ineffective, and progressive deterioration prevented further exploration and/or treatment. The child is still living, confined to his bed, at the age of 5 years. Case 2. Ultrasonography at the 30th week of pregnancy showed a tumor located near the brain stem with dilation of the entire ventricular system. Post mortem examination after abortion revealed a capillary and cavernous hemangioma. Case 3. Ultrasonography at the 34th week of pregnancy showed dilation of the ventricular system. As a result, birth was induced. CT scan and MRI of the newborn showed a mixed, solid and liquid, mass in the posterior fossa. Post mortem examination showed a papilloma of the choroid plexus. CONCLUSION: These rare congenital tumors are usually revealed by ultrasonography showing ventricular dilation. Advances in imaging techniques, especially MRI of fetal brain, should help in the management of such tumors. PMID- 8507139 TI - [Osteogenesis imperfecta with hypertrophic callus. Apropos of 2 cases with early onset]. AB - BACKGROUND: The callus that forms at the site of recent fractures in patients with osteogenesis imperfecta is usually normal, but hyperplastic callus may develop. CASE REPORTS: Case 1. A hyperplastic callus with local inflammation developed at the site of a fracture of the left thigh of a boy, aged 11 months suffering from osteogenesis imperfecta. This disease was characterized by the progressive development of broad limbs, bone islands on skull x-rays and blue sclerae. He had also had fractures at the ages of 4 and 7 months. Follow-up showed that this boy, now aged 15 years, had several fractures with the development of similar hyperplastic calluses. These limitated joint motility, causing him to remain confined to his bed. Case 2. This girl of consanguineous parents had a fracture of the femora at the age of 1 month; she had blue sclerae and developed a hyperplastic callus. The roentgenographic studies showed generalized osteopenia and deformities indicating osteogenesis imperfecta. CONCLUSION: Hyperplastic callus may develop in osteogenesis imperfecta. Its diagnosis may be difficult with neoplasms of bone, such as osteosarcoma, and its treatment is difficult. PMID- 8507140 TI - [Cochlear implants in children. Indications in rehabilitation of total deafness]. PMID- 8507141 TI - [Endomyocardial fibrosis in children]. AB - BACKGROUND: Recent advances in imaging techniques can facilitate the diagnosis of endomyocardial fibrosis. CASE REPORTS: Two cases of endomyocardial fibrosis were diagnosed in two Tunisian children, one aged 3 years and the other 12 years. Both were admitted with severe cardiac failure, predominantly of the right ventricule. Two dimensional echocardiography showed an apical amputation with echogenic material plus a thick, dense endocardial image, particularly at the level of the papillary muscles. The older child who also had cardiac catheterization, died 2 years later and the younger child died 4 years after diagnosis. Post mortem examination showed fibroelastic thickening of the endocardium and areas of fibrosis in the muscles of both children. CONCLUSIONS: The advantage of two dimensional echocardiography over other imaging techniques is that it can confirm the diagnosis of endomyocardial fibrosis and indicate the extent and degree of fibrosis. PMID- 8507142 TI - [Iconographic rubric. Pseudomyxoma peritonei complicating cancer of the rectum]. PMID- 8507143 TI - [Escherichia coli responsible of diarrhea]. PMID- 8507144 TI - [Sex ambiguity. Contribution of molecular genetics]. PMID- 8507145 TI - [Consensus conference on the treatment of purulent meningitis in infants and children]. PMID- 8507146 TI - [Efficacy and good tolerance of omeprazole in a case of refractory ulcerative esophagitis in the child]. PMID- 8507147 TI - [Apropos of immunostimulant treatments]. PMID- 8507148 TI - [Severe forms of visceral infantile leishmaniasis: early salvage treatment by antimonies]. PMID- 8507149 TI - [Arterial lesions after radiotherapy in children. Apropos of 16 cases]. AB - BACKGROUND: Arterial occlusive disease is an uncommon and rather unpredictable complication of radiotherapy in childhood. CASE REPORTS: Sixteen children (10 under 5 years of age and 7 under 3 years of age) who underwent radiotherapy for tumors between 1967 and 1983 developed an arterial occlusion with clinical manifestations during their follow-up. The radiotherapy dose was 25-55 Gy, and the fractionation was "conventional". The clinical manifestations depended on the site of arterial stenosis, including aorta and/or its branches (11 cases), carotid artery (3 cases) and limb arteries (2 cases). The delay before onset of clinical manifestations was variable, but generally very long (median: 13 years). Eight patients required surgical rehabilitation. CONCLUSION: Better management of this type of complication should benefit from the early screening of irradiated children, especially young children, given even moderate doses, and particularly those having received more than 40 Gy. PMID- 8507150 TI - [Investigation of the frequency of Japanese cedar pollinosis among university students in the year of freshmen and fourth grade]. AB - In investigations into Japanese cedar pollinosis, research on atmospheric pollen counts has been made in various parts of our country and progress in studies on the dominant causes has been made from the antigenic point of view. However, research into pollinosis of this kind from the physical point of view has been scant. The author has investigated the frequency of cases with Japanese cedar pollinosis every year since 1988 on the occasion of the periodical health examination of freshmen at our university. In this report are stated the results of the investigation into the frequency of sufferers of this kind among the 624 fourth grade students who were the subjects of investigation in 1988. The percentage of specific antibody carriers was found to have increased from 28.2% (1988) to 40.2% (1991), and the frequency of Japanese cedar pollinosis sufferers had also increased from 14.1% to 23.1%. In addition to this, 41 (43.6%) of the 94 students considered to be in danger of becoming sensitized to Japanese cedar pollen in 1988 had become pollinosis sufferers by 1991. This is significantly higher than the changes among the students considered to be in the borderline or symptom-free groups. From these results, it can be considered correct to regard subjects who are considered to be in danger of becoming sensitized as "reservists" to pollinosis. Follow up studies of and preventive treatment for these cases are necessary, because they are very likely to become pollinosis sufferers in the future. PMID- 8507152 TI - [A comparative study between urinary metabolites of sustained-release theophylline and theophylline clearance in clinical use]. AB - The relationships between changes in urinary metabolites and theophylline clearance were studied in 40 asthmatic children for each steady state phase. Urinary excretion of 1MU, DMU, 3MX increased with age. There were direct correlations between urinary metabolites, while urinary unchanged theophylline decreased and there was an inverse correlation between urinary metabolites. There was a significant correlation between the excretion of unchanged theophylline and 3MX (r = 0.597, p < 0.0001). The values of renal clearance and hepatic clearance also decreased with age. The changes in hepatic clearance were greater than those of renal clearance and showed a low correlation with unchanged theophylline (r = 0.247, p < 0.002), while the changes in renal clearance were high correlation with those of unchanged theophylline in urine. These changes were significant (r = 0.833, p < 0.0001). The changes in theophylline metabolites and its clearance are clinically important because the effective therapeutic range is narrow. Therefore, we concluded that it would be useful to determine the appropriate administration schedule of theophylline considering changes in renal clearance and urinary unchanged theophylline in different age groups. PMID- 8507153 TI - Characteristics of airway responses in patients with bronchial asthma. Evaluation of asthma classification systems based on clinical symptoms and clinical findings. AB - Asthma was classified into three types according to clinical symptoms (clinical diagnosis, C.D.): Ia. simple bronchoconstriction type (further divided into two subtypes, type Ia-1 with 0-49 ml/day of expectoration and type 1a-2 with 50-99 ml/day); Ib. bronchoconstriction + hypersecretion type, and II. bronchiolar obstruction type. Asthma was also classified by a score related to clinical findings and examinations (score diagnosis, S.D.). The clinical features of each type of asthma according to the two classifications methods were compared. Type 1a-2 and 1b patients (C.D.) were characterized by mucus hypersecretion (more than 50 ml/day) and eosinophilia in the bronchoalveolar lavage (BAL) fluid. The characteristic findings for type II asthmatics (C.D.) were a lower %V25 value (less than 10%) and an increased proportion of neutrophils (more than 20%) in the BAL fluid. All of the patients classified as types 1a-1, Ib, and II by clinical diagnosis were evaluated as having the same types of asthma by score diagnosis. Patients with type Ia-2 evaluated by clinical diagnosis were classified as type Ib by score diagnosis, since these two types had similar pathophysiological features represented by the increased proportion of eosinophils in the BAL fluid. PMID- 8507151 TI - An airway hyperresponsiveness model in rat allergic asthma. AB - We attempted to obtain a new airway hyperresponsiveness model using DNP-Ascaris extract (DNP-Asc)-induced rat allergic asthma. Male Wistar rats were actively sensitized with DNP-Asc, and challenged in a non-anesthetized state by inhalation of the antigen for 10 min in a chamber. One, 6 and 24 hr after DNP-Asc challenge, the responsiveness of the airway smooth muscles to inhaled acetylcholine (ACh) was determined using a modified Konzett-Rossler method under anesthesia. Twenty four hr after the challenge, a significant and marked airway hyperresponsiveness was seen. The increase in airway responsiveness was significantly inhibited by pretreatments with a leukotriene antagonist, ONO-1078, and a thromboxane synthetase inhibitor, ozagrel, and tended to be inhibited by a PAF antagonist, CV 3988. The hyperresponsiveness induced by DNP-Asc challenge was accompanied by airway inflammation determined by dye exudation. From the above results, it is indicated that a model of airway hyperresponsiveness was established in rats with allergic asthma, and that the chemical mediators involved in the response might be leukotrienes, thromboxane A2 and PAF. PMID- 8507154 TI - [Specific IgE antibody titers to hen's egg white lysozyme in allergic children to egg]. AB - Hen's egg white lysozyme (HEL) is one of the minor allergen in hen's egg white. HEL is commonly used to treat disease of respiratory tract, because it have the effect to dissolve mucopolysaccharide and anti-inflammatory action. We examined specific IgE antibody titers (IgE-HEL) in patients with egg allergy and allergic patients to other antigen than egg. Results indicated that 16.37 +/- 29.56 (PRU/ml) (mean +/- SD) of IgE-HEL was found in 30 out of the 39 allergic patients to egg, and 23 (66.7%) out of the 39 patients studied showed RAST scores of more than 2. On the other hand, 1.08 +/- 0.92 (PRU/ml) of IgE-HEL in 12 out of the 44 allergic patients to other antigen than egg, and 5 (11.4%) out of the 44 patients studied showed RAST scores of more than 2. Moreover, we treated a patient who developed anaphylaxis after taking HEL. 1.0 (PRU/ml) of HEL-IgE was found in this patient. These results suggest that we should be careful in treating allergic patients with HEL. PMID- 8507155 TI - [Allergen analysis of buckwheat by the immunoblotting method]. AB - Inhalation or ingestion of very small amounts of buckwheat allergen can initiate severe symptoms including wheezing, rhinorrhea, urticaria, vomiting and anaphylactic shock in patients with hypersensitivity against buckwheat. However, few studies of the immunological properties of buckwheat allergen have been made. The aim of the present investigation was to analyze the allergen in buckwheat antigen using the immunoblotting method, radioallergosorbent test (RAST) and RAST inhibition assay. Buckwheat 24 kilodalton protein (BW24KD) was shown by immunoblotting analysis to be the most frequently recognized allergenic component, binding to IgE antibodies from 100% of the patients' sera. There was a significant positive correlation (p < 0.001) between % bindings for BW24KD and buckwheat. In the RAST inhibition assay using patients' sera which showed positive IgE antibodies to buckwheat and BW24KD, there was effective inhibition in a dose-dependent manner between inhibition in a dose-dependent manner between BW24KD and buckwheat. These data indicated that BW24KD was a major allergen in buckwheat antigens. The experiments of SDS-PAGE using digestion buffer with or without 2-mercaptoethanol suggested that BW24KD was a component of heterodimer and the paired components had different molecular weights. PMID- 8507156 TI - [Difference of immunogenicity evoking in rabbits after immunization with a low molecular antigen by various routes]. AB - The present studies were undertaken to clarify the difference of the immunogenicity evoked in rabbits immunized with a low-molecular chemical antigen (TNBS) alone, by four administration routes. Rabbits were divided into four experimental groups: TNBS sc group, i.v. group, im group and ip group (3 times/week, 10 times in total), and immune responses to TNBS were estimated by the assay systems of humoral immunoreactions (HA.PCA.Arthus) and cellular immunoreaction (DTH). The highest evoking of the immunogenicity to TNBS was noted in the sc group in the case of humoral immune response, whereas the lowest evoking in the i.v. group. The intermediate degree of the immunogenicity was elicited in the im and ip groups. On the other hand, only the sc group displayed positive cellular immune response (DTH), while such immune response was never recognized in the i.v., im and ip groups. These results were indicated that the immunogenicity to the low-molecular antigen (TNBS) was evoked exceedingly in rabbits by sc sensitization route from view of humoral and cellular immune responses. PMID- 8507157 TI - [The influence of rush immunotherapy on the production of interleukin-5 from mononuclear cells]. AB - We investigated the influence of rush immunotherapy (RI) on the production of interleukin (IL)-5 from peripheral blood mononuclear cells (PBMC) in asthmatics sensitive to Dermatophagoides farinae (Df). The levels of IL-5 produced varied among the subjects, and these levels were not affected by the addition of Df, regardless of RI. When IL5 levels were individually compared before and after RI, some cases demonstrated an apparent decrease in production at 16 weeks after RI. It is considered that further study will be needed to confirm whether or not immunotherapy can truly suppress the production of IL-5. PMID- 8507158 TI - Soluble interleukin-2 receptor in sputum from patients with bronchial asthma. AB - To evaluate the activation of T-lymphocytes in the airways of patients with asthma, we attempted to measure the concentration of soluble interleukin-2 receptor (sIL-2R) in sputum extracts from asthma patients with acute attacks or in remission. The large amount of alkaline phosphatase in the sputum extracts excluded the use of an ELISA kit. Measurement was attempted by radiolabeling the second antibody in the ELISA kit. sIL-2R was detectable in 10/23 (43%) of the sputum extracts from patients with acute asthma attacks, but not in those from patients in remission (n = 12, p < 0.02). These observations suggest that T lymphocyte activation takes place in the airways of patients with acute asthma attacks. PMID- 8507159 TI - [Increased plasma levels of platelet-activating factor (PAF) and low serum PAF acetylhydrolase (PAFAH) activity in adult patients with bronchial asthma]. AB - We studied the relationship between the blood levels of platelet-activating factor (PAF) and the activity of serum PAF acetylhydrolase (PAFAH), an enzyme that inactivates PAF, in adult patients with bronchial asthma. The PAF levels in the blood and the PAFAH activity in the serum obtained from adult patients with bronchial asthma in remission (137 cases) and from healthy adult controls (106 cases) were determined by radioimmunoassay (RIA) and compared. The following results were obtained. 1. The plasma levels of PAF were significantly higher in the patients with bronchial asthma in all severity groups (mild, moderate, and severe) and all asthma types (atopic, mixed, and infectious) than in the healthy controls (p < 0.001). However, no significant differences associated with the severity and type of asthma were noted. 2. Serum PAFAH activity was significantly lower in the patients with bronchial asthma in all severity groups (mild, moderate, and severe) and asthma types (atopic, mixed, and infectious) than in the healthy controls (p < 0.001). However, no significant differences associated with the severity and type of asthma were noted. 3. PAF/PAFAH in the patients with bronchial asthma showed no significant difference associated with the severity and type of asthma. 4. There was not a significant correlation between plasma levels of PAF and serum PAFAH activity in the patients with bronchial asthma. It was, therefore, suggested that the significantly high plasma PAF levels and the significantly low serum PAFAH activity in asthmatic adults compared to the respective values in healthy controls may explain one of the mechanisms of the development and persistency of adult bronchial asthma. PMID- 8507160 TI - [Basophilic cells/eosinophil differentiation activity in conditioned medium of nasal inverted papilloma]. AB - An increased number of histochemically distinct mast cells and eosinophils can be observed in the tumor mass of nasal inverted papilloma. In order to elucidate the mechanism of this accumulation of mast cells and eosinophils in a local site, we examined the activity of conditioned medium (CM) in inducing differentiation and proliferation of basophilic cells and eosinophils from hematopoietic progenitors of peripheral blood mononuclear cells of the patients with allergic diseases. CM was obtained by the culture of nasal inverted papilloma cells (NIPC) and its activity was measured by determining colony proliferation in methylcellulose assay for 14 days. In the 14 day methylcellulose assay, the number of Eo-type colonies in the presence of 1, 5, 10 and 20% CM was significantly higher than the baseline number of Eo-type colonies (0%). Cytochemical analysis confirmed that the number of colonies of cells with metachromatic granules and histamine positive colonies in Eo-type colonies in the presence of 5, 10 and 20% NIPC-CM was significantly higher than that in the control. The number of ECP positive colonies in Eo-type colonies in the presence of 5% and 10% CM was also significantly higher than in the presence of 0.5% CM. Furthermore both histamine and ECP positive colonies were observed in Eo-type colonies. These results are consistent with the hypothesis that basophilic cells and eosinophils accumulate at nasal inverted papilloma sites at least in part by the recruitment of progenitors from the circulation and subsequent differentiation in situ in response to cytokines. Eosinophils and basophilic cells also commonly originate from committed granulocyte progenitors. PMID- 8507161 TI - Is nonpulsatile blood flow detrimental to patients? PMID- 8507162 TI - The beginning of the artificial kidney. PMID- 8507163 TI - Beneficial circulatory support by left heart bypass with a centrifugal (BioMedicus) pump for aneurysms of the descending thoracic aorta. AB - A comparative study between left heart bypass with a centrifugal (BioMedicus) pump and with a temporary external shunt was performed to assess the efficacy of distal organ perfusion in the surgical treatment of 31 patients with aneurysm of the descending thoracic aorta. Eighteen patients were supported with a centrifugal pump, and the remaining 13 were supported by temporary shunt with either a Gott shunt or a Dacron graft. Heparinless bypass with a centrifugal pump provided a significant decrease of intraoperative blood loss and blood transfusion by the combined application of Cell-Saver. The pressure difference between upper and lower extremities decreased (p < 0.05) in the centrifugal pump group even with aortic cross-clamping, and the urine output increased during operation. Among 13 patients supported with the temporary shunt, 3 had postoperative renal failure, and 2 died of it. All patients with a centrifugal pump survived without any complications. It could be concluded that the left heart bypass with a centrifugal (BioMedicus) pump was safe and was favorable for support of the distal circulation during aortic cross-clamping and to prevent ischemic complications such as renal failure and spinal cord injury. PMID- 8507164 TI - A flow visualization study of centrifugal blood pumps developed for long-term usage. AB - We have developed centrifugal pumps for long-term circulatory assistance, with the final goal of a completely implantable ventricular assist device or total artificial heart. The previous model, NCVC-0, was characterized by a nonseal design and few flow-stagnating parts and acquired high durability and antithrombogenicity. To improve its pumping performance, NCVC-0 was modified. In the new model, NCVC-1, the profile shape of the impeller was changed from flat to conical, the number of vanes from 4 to 6, and the vane entrance angle from 30 degrees to 60 degrees. A flow visualization study performed by means of a combination of the polystyrene tracer method and the light-cutting method indicated decreased flow turbulence between vanes in NCVC-1, which corresponded well with the increased pumping performance. Flow visualization is a useful method to evaluate the design elements that are closely related to the pumping performance of a centrifugal blood pump. PMID- 8507165 TI - Development of an all-in-one percutaneous cardiopulmonary support system. AB - This paper deals with development of an all-in-one percutaneous cardiopulmonary support (PCPS) system. In recent years, PCPS has been used for the treatment of acute myocardial infarction. A prototype of a compact all-in-one PCPS system was developed. The system contains a centrifugal pump and an extra-capillary flow type membrane lung in one body. The system has a priming volume of 250 ml, which allows for PCPS with no additional blood. The in vitro tests and an ex vivo test were conducted. The system produces 1.6-5 L/min of flow in the experiments. The O2 transfer rate was 310 ml/min, and the CO2 transfer rate was 300 ml/min at a blood flow rate of 5 L/min. This device is compact, requires less priming volume than a standard system, and is easy-to-handle in the experiments. The system is considered applicable to percutaneous cardiopulmonary support. PMID- 8507166 TI - The renin-angiotensin-aldosterone system and hematologic changes during pulsatile and nonpulsatile cardiopulmonary bypass. AB - The effects of pulsatile and nonpulsatile cardiopulmonary bypass using a roller pump on levels of vasoactive hormones and hematologic changes were studied in 32 patients subjected to elective primary coronary artery bypass graft surgery. Seventeen patients had nonpulsatile perfusion (nonpulsatile group) and 15 patients had pulsatile perfusion (pulsatile group) during the period of cardiac arrest. Vasoactive hormones (plasma renin, angiotensin II, aldosterone, epinephrine, and norepinephrine) were measured in these patients. In order to clarify hematologic changes, plasma free hemoglobin, number of platelets, platelet factor 4, and beta-thromboglobulin were measured. There were no significant differences between the pulsatile and nonpulsatile groups with regard to vasoactive hormones and damage of platelets. In the pulsatile group, however, the rise of plasma free hemoglobin levels was significantly higher than that in the nonpulsatile group during and after cardiopulmonary bypass. We did not see the benefit of pulsatile perfusion using a roller pump on vasoactive hormones. Evidence of increased hemolysis with pulsatile flow was demonstrated in our cases. PMID- 8507167 TI - Development of the Terumo Capiox centrifugal pump and its clinical application to open heart surgery: a comparative study with the roller pump. AB - We have developed the Terumo Capiox centrifugal pump (CXP), which consists of a rotor having a unique straight-path design to reduce pump rotational speed without decreasing hydraulic efficiency. The CXP was tested in vitro for blood trauma with a specially designed test circuit using fresh bovine blood. The Biopump (BP) (Medtronic, Minneapolis, MN, U.S.A.) and the roller pump (RP) were used as controls. The CXP demonstrated the smallest elevation of free plasma hemoglobin compared with the BP and the RP. The CXP was then applied to cardiopulmonary bypass (CPB) in 10 patients (CXP group) who underwent elective coronary artery bypass grafting (CABG), and the results were compared with those for a comparable roller pump group (RP group). Free plasma hemoglobin level, platelet count, and serum beta-thromboglobulin (beta-TG) level were measured during CPB. There were no CXP-related complications nor hemodynamic abnormalities during CPB. The CXP group demonstrated less hemolysis and less platelet depletion than the RP group. Furthermore, the serum beta-TG level was significantly lower in the CXP group than in the RP group. The CXP showed excellent hemodynamic performance with less blood trauma both in vitro and in clinical application to open heart surgery. Thus, the CXP has significant potential to be safely applied to CPB for open heart surgery and circulatory support. PMID- 8507168 TI - Comparison of a new and a standard single-needle dialysis system using a mathematical model. AB - Two single-needle dialysis systems are compared for their hydrodynamic and kinetic behavior, the classic double-headed pump system and a newer bidirectional blood pump. First, discharges and pressures are calculated in a time-space grid to learn about the flow characteristics of the single-needle systems. These parameters are important for they control ultrafiltration and clearance rates in the artificial kidney. Also, the influence of different artificial kidneys and expansion chambers on the flow parameters is studied. Second, starting from these results, the removal of urea and creatinine is simulated using a double-pool model for both a normal dialysis session and an ultrashort daily autodialysis. As a result, the use of a single marker molecule to study or characterize solute removal is questioned. The new blood pump is able to perform dialysis filtering equivalently to the classic system but has its own specific advantages. PMID- 8507169 TI - Clinical evaluation of a new dialyzer, FLX-12 GW, with a polyester-polymer alloy membrane. AB - The performance of a membrane in renal failure therapy is determined by its structure, its overall mass transfer properties, and its blood compatibility. In this regard, removal of beta 2-microglobulin (beta 2M) has become a major objective of dialysis therapy. In the present study, a newly developed high-flux membrane composed of a polyester-polymer alloy (PEPA) with the components of polyarylate and polyethersulfone (dialyzer FLX-12 GW; Nikkiso Co., Japan) has been evaluated with regard to both biocompatibility and elimination capacity for beta 2M during hemodialysis of 8 stable chronic uremic patients. The clearance values of low molecular weight solutes were in the same range as those reported for high-flux dialyzers of comparable surface area. There was no drop in leukocyte counts and only a minimal fall in platelet counts nearly in the same range as has been observed by other investigators using polyamide membrane. C3a Des Arg generation was low, and C5a Des Arg formation was not significantly influenced. There was a sharp drop in the serum beta 2M level (-35%) during dialysis with a clearance between 59.7 +/- 5.6 ml/min (QB 200 ml/min) and 70.1 +/ 9.7 ml/min (QB 300 ml/min), respectively. Accordingly, the sieving coefficient was calculated to be 0.2 at 30 min after start of dialysis and 0.6 1 h later. The membrane was able to remove 184.0 +/- 22.3 mg/4 h due to an apparent rate of adsorption during the first hour of treatment in combination with high transmembrane transfer in the following time. PMID- 8507170 TI - Permanent cardiac pacing after cardiac operations. AB - From January 1980 through December 1990, implantation of a permanent pacemaker was performed in 34 patients following open heart surgery. The patients were divided into two groups according to the clinical indications for implantation of permanent pacemakers. Group 1 (9 patients) had surgical atrioventricular block, and Group 2 (25 patients) had sick sinus syndrome. Tricuspid valve surgery was involved in 67% of Group 1 and 64% of Group 2. Adams-Stokes syncopal attack was the prime indication for permanent pacing in 100% of Group 1 and in 72% of Group 2. There were 2 operative deaths in Group 1, and no deaths in Group 2 (22% in Group 1 vs. 0% in Group 2, p < 0.005). Causes of the deaths were not related to the pacemaker implantation but to congestive heart failure following surgery. Among 32 survivors, there were 2 late deaths in Group 1, and 4 deaths in Group 2 (25% in Group 1 vs. 16% in Group 2, p < 0.05). The overall actuarial survival rate at 10 years was 82.1 +/- 2.8%. However, the actuarial survival rate of patients in Group 1 is 70.2 +/- 4.1%, which is statistically less than 85.4 +/- 2.2% in Group 2 (p < 0.01). As judged by these results, patients in Group 1 should be followed on a regular out-patient basis even if they are asymptomatic and there is no evidence of pacemaker failure. PMID- 8507171 TI - Chronic effects of a cardiac assist device on the bulk and regional mechanics of the failed left ventricle in goats. AB - Pneumatically driven, diaphragm-type left ventricular assist devices (LVADs) were implanted into 8 goats with profound induced infarction to the left ventricle by using multiple ligations of the left anterior descending (LAD) coronary artery as well as small arteries in the LAD distribution area. Left ventricular diameters, regional myocardial segment lengths, and wall thicknesses were measured by sono micrometers. After left ventricular function seemed to be recovered, the goats were weaned off the LVADs after a gradual decrease of pump bypass flow over several days. Thereafter, hemodynamic and cardiac parameters were observed for about 1 month more. Three animals recovered successfully owing to the LVAD pumping. Before starting pump-weaning procedures, the bulk mechanical work (BMW) done by the left ventricle during LVAD pumping and under temporary pump-off conditions was 0.08 +/- 0.01 (mean +/- SE) and 0.22 +/- 0.01 W/100 g left ventricular weight (LVW), respectively, while the regional mechanical work done by the normal myocardium (RMWn) was 1.5 +/- 0.4 and 4.3 +/- 0.9 mW/cm3 during pumping and under temporary pump-off conditions, respectively. BMW and RMWn values obtained under pump-on conditions both increased gradually during the weaning process. Even after pump removal, they continued to increase and reached constant values of about 0.3 W/100 g LVW and 10 mW/cm3, respectively, around 2 weeks after pump removal. Although the myocardium in the infarction area did no work for the first several days after surgery, it recovered to do some external work with the aid of LVAD pumping. However, recovery of left ventricular function owed more to compensatory increases in pumping ability of the remaining normal myocardium than to recovery of the damaged myocardium. The LVAD could salvage severely damaged hearts unless the infarction area exceeded 50% of the left ventricular wall. PMID- 8507172 TI - Early experimental studies on hemoperfusion as a treatment modality for acute radiation disease. AB - First results of the studies on hemoperfusion therapy of acute radiation disease that were conducted in Kiev in 1976 are presented. In these studies, 69 mongrel dogs were exposed to irradiation at a dose of 525 rad (5.25 Gy). It was proved that hemoperfusion through uncoated synthetic activated carbons led to a noticeable increase in their survival rate, from 3.2% in the control group (n = 31) to 68.4% and 62.4% for the dogs that received extracorporeal treatment at 2 h (n = 19) and 24 h (n = 19) after irradiation, respectively. PMID- 8507173 TI - The PUCA pump: a left ventricular assist device. AB - Left ventricular assist devices (LVADs) that are being used clinically still have specific drawbacks. Therefore, a new concept for mechanical circulatory support was developed, the pulsatile catheter (PUCA) pump. It consists of an extracorporeally placed, pneumatically driven membrane pump that is connected to a valved catheter. The catheter is introduced into an easily accessible artery and positioned with its distal tip in the left ventricle. Blood is aspirated from the left ventricle and ejected into the ascending aorta. Potential advantages of the catheter pump are its simple design and its fast application with minimal surgery. Preliminary in vitro tests with a first prototype showed that it is possible to create a pulsatile flow of 3 L/min and proved that further developing the PUCA pump will be worthwhile. PMID- 8507174 TI - Small soft left ventricular assist device powered by intraaortic balloon pump console for infants: a less expensive option. PMID- 8507175 TI - Structural changes in the N-linked sugar chains of serum immunoglobulin G of HTLV I transgenic mice. AB - IgGs were purified from the sera of HTLV-I transgenic and nontransgenic mice. Comparative studies of the N-linked sugar chains released by hydrazinolysis revealed that their structures of transgenic IgG are quite different from those of nontransgenic IgG. Although both IgGs contained biantennary complex-type oligosaccharides, transgenic IgG had more agalactosylated forms (45%) than those from nontransgenic IgG (28%), just as was found in patients with rheumatoid arthritis (RA). Since these transgenic mice express arthritis similar to RA, it will be a useful model to investigate the relationship between the galactosylation of IgG and the development of RA. PMID- 8507176 TI - Pyroelectric current of oriented purple membrane films. AB - By applying an electric field(2 to 5.5 Volt/mm) to a suspension of purple membrane from Halobacterium halobium, oriented purple-, purple blue-, and blue colored membrane films have been formed on conductive glasses. Pyroelectric currents have been found for these three types of oriented films at temperatures between 25 and 160 degrees C. The oriented purple-colored membrane (PM) film has positive current peaks at around 60, 80, and 115 degrees C and reverses its sign at around 130 degrees C, followed by a negative peak at 145 degrees C. (Instead of the positive peak at 80 degrees C, a negative peak has been found around 90 degrees C for purple blue- and blue-colored membrane films.) The current peak at 80 degrees C for the PM film could be due to a conformational change in the protein, which includes at least a change in the environment of the chromophore. The sign-reversal current at 130 degrees C for the PM film seems to be related to denaturation of the protein. These peak temperatures in the pyroelectric current of the PM films, i.e., 60, 80, and 115 degrees C, have been found to agree well with some characteristic temperatures observed by Shnyorov et al. (D-H exchange), Jackson et al. (DSC and absorption spectra of visible light), and Hiraki et al. (X-ray, absorption spectra). PMID- 8507177 TI - Rat 12-lipoxygenase: mutations of amino acids implicated in the positional specificity of 15- and 12-lipoxygenases. AB - Site directed mutagenesis, based on the polymerase chain reaction, was carried out on a rat 12-lipoxygenase cDNA within a region that encodes several amino acids believed to be of importance for the positional specificity of 15- and 12 lipoxygenases. The following mutants were constructed to increase the 15 lipoxygenase activity of rat 12-lipoxygenase; [Leu397]12-lipoxygenase, [Ile389, Leu397]12-lipoxygenase, [Gln416]12-lipoxygenase, [Ile417]12-lipoxygenase, and [Gln416, Ile417]12-lipoxygenase. Each mutated cDNA was expressed in Escherichia coli and 12- and 15-lipoxygenase activity was assayed in the 10,000 x g supernatants of homogenized cells. When compared to wild type enzyme, none of the mutants exhibited significantly increased 15-lipoxygenase activity. Thus, considering the primary structure of wild type enzyme and our results of mutagenetic replacements, we have not found evidence indicating that amino acids in positions 416, 417, or 418 are critical for the positional specificity of rat 12-lipoxygenase. PMID- 8507178 TI - Evidence for a detectable delta-6-desaturase activity in rat heart microsomes: aging influence on enzyme activity. AB - This study represents the first report indicating that rat heart microsomes contain a measurable delta-6-desaturase activity. The aging process affects delta 6-desaturase activity in the heart to a lesser extent than in the liver, supporting the hypothesis that the regulation of the individual desaturase enzymes may differ in these two tissues. Although decreased desaturase activity, considered alone, may be expected to lower polyunsaturated fatty acid levels, in old animals no modifications in heart microsome fatty acid composition were observed. Probably other metabolic changes may offset this effect, leading to the maintenance of arachidonic acid level in the heart. PMID- 8507179 TI - Defining the statistical distribution of vesicle diameters facilitates quantitative assessment of spectral narrowing from small vesicles in protein/lipid interaction studies by 2H-NMR. AB - The diameters of vesicles comprising complexes of an integral membrane protein and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, deuterated in the choline gamma methyl groups, exhibited a lognormal distribution defined by the geometric mean (GM) and the logarithmic standard deviation (LSD). The range of vesicle sizes within each complex was very large (e.g., 99% of vesicles measured between 60 nm and 4,000 nm in one complex). This complicated assessment of spectral narrowing artefacts from small vesicles in broad line 2H-NMR results. Artefacts (e.g., decreases in quadrupole splitting and generation of two component spectra) resembled results attributed to membrane proteins in other 2H-NMR studies for which spectral narrowing was dismissed by demonstration of some vesicles > 400 nm in diameter. This was inadequate since 2H-NMR spectra from complexes with GM < 350 nm exhibited spectral narrowing artefacts despite the presence of some vesicles 1,200 nm in diameter. The nature and degree of artefact were determined by both GM and LSD. Quantifying vesicle sizes by GM and LSD accommodated the large size variation within a complex and facilitated quantitative assessment of artefacts through comparison of different complexes. PMID- 8507181 TI - Solution conformation of the tetrasaccharide glycoside Xyl beta 1-(Man alpha 1 3)2Man beta 1-4Glc beta 1R from the mollu-series glycosphingolipids. AB - The conformation of Xyl beta 1-(Man alpha 1-3)2Man beta 1-4Glc beta 1 OCH2CH(N3)CH(OH) CH = CHC13H27 tetrasaccharide glycoside in Me2SO-d6 was investigated with use of a distance mapping procedure based on rotating-frame NOE and hydrogen bond constraints, and Molecular Mechanics calculations. The Man alpha 1-3Man beta linkage was found to be well defined in a single conformation, whereas some flexibility could be assumed for the remaining two glycosidic linkages. Similar conclusions, though based on a smaller number of constraints, were drawn for the title compound anchored in mixed D2O/dodecylphosphocholine-d38 micelles. PMID- 8507180 TI - Murine bone morphogenetic protein-4 gene: existence of multiple promoters and exons for the 5'-untranslated region. AB - A murine genomic clone of about 16 kilobases encompassing putatively entire bone morphogenetic protein (BMP)-4 gene has been isolated. Comparison with the cDNA clones revealed the existence of at least five exons on the 3' side of the clone. There are two alternative transcriptional start sites, one is for the first exon the other for the second, the resulting exon organization in mRNA is I-III-IV-V and II-III-IV-V, respectively. The coding region is dispersed between exons IV and V. Both promoter regions carry no canonical TATA box but carry GC rich sequences. PMID- 8507182 TI - Progesterone induced expression of alkaline phosphatase is associated with a secretory phenotype in T47D breast cancer cells. AB - In our previous work we reported on stimulation of a tissue unspecific alkaline phosphatase (liver/bone/kidney, L/B/K) in the human breast cancer cell line T47D by progestins. Here we show that in these cells the synthetic progestin R5020 (Promegestone) induces transcription of a 2.7-kilobase ALP mRNA. In this cel line, maximal induction is reached after 24 hours, decreases to 50% after 72 hours and is sensitive to inhibitors of protein synthesis. The induction of ALP mRNA and enzyme activity is specific for R5020 and dexamethasone and is completely inhibited in the presence of 10(-7) M RU486. When treated with R5020 for 48 hours, T47D cells exhibit a substantially altered phenotype, lipid vacuoles accumulate all over the cytoplasm, conferring to the cells a secretory morphology. This phenotype is associated with increased ALP enzyme activity which is also maximal at 48 hours. This effect is progestin specific since other steroids do not lead to the same macroscopical changes. PMID- 8507183 TI - Voltage sensitivity of the osteoclast calcium receptor. AB - We demonstrated previously that osteoclasts possess a divalent cation-sensitive "receptor", the Ca2+ receptor. Activation of the Ca2+ receptor by the surrogate cation Ni2+ was shown to elicit an increase in cytosolic [Ca2+] to a peak value followed by an exponential decline. In the present study we examined the influence of surface membrane voltage on the kinetics of Ca2+ receptor inactivation. The K+ ionophore, valinomycin was applied to intercept the declining phase of the cytosolic [Ca2+] transient elicited by application of between 50 microM- and 5 mM-[Ni2+]. This resulted in a sustained elevation of cytosolic [Ca2+] or even a 'hump' followed by a gradual decline. Such a kinetic alteration persisted in a Ca(2+)-free solution, but was abolished in high extracellular [K+] (105 mM). Thus, we demonstrate for the first time to our knowledge, a modulatory effect of membrane potential on the function of the osteoclast Ca2+ receptor. PMID- 8507184 TI - A novel "active" form of proteasomes from Xenopus laevis ovary cytosol. AB - The cytosol fraction prepared from Xenopus laevis ovaries by one-step ultracentrifugation catalyzed the hydrolysis of succinyl-leucyl-leucyl-valyl tyrosine-4-methylcoumaryl-7-amide with or without SDS, an activator of 20S latent proteasomes. Both activities were lost on immunodepletion with antibodies against 20S proteasome. Storage of the cytosol at 4 degrees C led to abolition of the SDS independent activity, but not the SDS-dependent activity. Upon DEAE-cellulose chromatography, the enzyme catalyzing the SDS-independent activity could be separated from that responsible for the SDS-dependent activity. These results indicate that the ovary cytosol contains a large proportion of a novel, "active" form of proteasomes which does not require SDS but is unstable and is readily converted to a latent form which requires SDS. ATP is known to stabilize 26S protease complex, but ATP reduced SDS-independent activity. It seems that the "active" form of proteasomes (molecular weight: about 1000-kDa) is different from 26S protease complex. PMID- 8507185 TI - Isolation of a cellobiohydrolase of Clostridium thermocellum capable of degrading natural crystalline substrates. AB - A cellobiohydrolase (CBH3) of Clostridium thermocellum was isolated from the recombinant strains of Escherichia coli. The enzyme was shown to have a Mr of 78 kDa and isoelectric point of 4.75. The hydrophilic nature of the enzyme was confirmed by its unretarded elution on gel filtration column. The enzyme had a binding affinity for the microcrystalline substrate (Avicel). The pH and temperature optimum were determined as 6.5 and 60 degrees C. The enzyme was found to be active on p-nitrophenyl cellobioside, carboxymethyl cellulose, Avicel, amorphous cellulose, lichenan and xylan. The most distinguishing feature of CBH3 was the degradation of a variety of natural crystalline substrates, with maximum activity on filter paper. The enzyme was tolerant to high levels of cellobiose, susceptible to heavy metals and was protected by DTT and calcium at higher temperatures. This is the first report of a highly active cellobiohydrolase produced in C. thermocellum. PMID- 8507186 TI - Erythropoietin receptor binds to Friend virus gp55 through other membrane components. AB - Direct interactions of Friend spleen focus-forming virus glycoprotein gp55 with either erythropoietin receptor (EpoR) or interleukin (IL)2 receptor beta chain (IL2R) (but not with IL3 receptor) have been reported to induce factor independent prolonged proliferation of erythroid or lymphoid cells. In order to clarify the molecular mechanism by which EpoR-gp55 complex transmits an aberrant growth signal in the absence of erythropoietin, various chimeric receptors constituted with IL2R, EpoR or IL3 receptor were constructed. It was found that coexpression of gp55 and the chimeric receptors containing the cytoplasmic domains of EpoR and the extracellular domains of IL3 (or IL2) receptor in IL3 dependent Ba/F3 cells results in factor-independent growth. Since gp55 in cell membrane has only a two amino acid tail in the cytoplasmic domains and thus cannot interact with EpoR in cytoplasm, our data suggest that gp55 does not bind EpoR directly but interacts with EpoR through third membrane component(s). PMID- 8507188 TI - Localization of the chaperone binding site. AB - The hypothesis derived from models of the multi-oligomeric chaperone complex suggests that partially denatured proteins bind in a central cavity in the aggregate. To test this hypothesis, the molecular chaperone, alpha crystallin, was bound to partially denatured forms of gamma crystallin, and the binding site was visualized by immunogold localization. In an alternative approach, gold particles were directly complexed with gamma crystallin, followed by binding to the alpha crystallin aggregate. In both cases, binding was localized to the central region of the aggregate, confirming for the first time that partially denatured proteins do indeed bind to a central region of the molecular chaperone aggregate. PMID- 8507187 TI - Translocation of retinoblastoma protein associated with tumor cell growth inhibition. AB - Immunocytochemistry revealed an association between growth inhibition and a translocation of retinoblastoma protein (pRB) to the nucleoli of U-2 osteosarcoma cells inhibited in their growth by the negative growth factor NCPI (natural cell proliferation inhibitor). Similar phenomenon was demonstrated by Western blot analysis and immunocytochemistry in U937 leukemic cells inhibited in their growth and induced to differentiate by 12-O-tetradecanoylphorbol acetate (TPA). Total nuclear extract of control U937 cells gave an intense 110 KD band, while total nuclear extract of TPA treated cells produced an intense 60 KD band and a weak 110 KD band. No bands were observed for the purified nucleoli of control cells, but the purified nucleoli of TPA treated cells produced a 60 KD band. These results suggest that in the process of cell growth inhibition and differentiation, specific proteolysis of pRB and its translocation to the nucleolus may occur. PMID- 8507189 TI - Role of extracellular Na+ on CCK-8-induced insulin secretion. AB - CCK-8 stimulates insulin secretion by an effect involving phosphoinositide (PI) hydrolysis and release of Ca2+ from intracellular stores. In this study, we examined the dependence of Na+ for the effects of CCK-8. CCK-8 (100 nM) stimulated insulin secretion from isolated rat islets. A first phase, which lasted 10 min, was not affected by removal of external Na+, whereas a second phase was abolished. CCK-8-stimulated 45Ca2+ and 3H efflux in 45Ca(2+)- and myo [2-3H]-inositol-prelabelled islets were not affected by removal of external Na+. In a second series of experiments, pancreatic rat islet cells were loaded with the Ca2+ fluorophore FURA 2-AM. CCK-8 (100 nM) induced a rapid and transient increase in the cytoplasmic free Ca2+ concentration ([Ca2+]IC), followed by a subsequent reduction of [Ca2+]IC below the prestimulatory levels. The CCK-8 induced increase in [Ca2+]IC was not dependent on extracellular Na+, whereas the decline in [Ca2+]IC after the initial peak was slower in the absence than in the presence of Na+. Thus, the present study shows that both the second phase of CCK 8-stimulated insulin secretion and the CCK-8-stimulated postpeak reduction in [Ca2+]IC are dependent on extracellular Na+. PMID- 8507190 TI - Human cartilage from late stage familial osteoarthritis transcribes type II collagen mRNA encoding a cysteine in position 519. AB - A single base change resulting in the substitution of Cys for Arg at position 519 of the type II collagen triple helix is a predisposing factor in the pathogenesis of a precocious-onset form of familial osteoarthritis associated with a mild chondrodysplasia. Cartilage obtained at the time of total knee replacement in a patient with the Arg-Cys519 mutation was used to investigate the expression of Col2A1 alleles. Using PCR assisted amplification of mRNA with specific amplification of a region of Col2A1 message encompassing exons 31-34, followed by single strand conformation polymorphism and sequence analyses, we have found transcription products of both mutant and normal type II collagen alleles. Further analysis of the sequence of these exons provides evidence that the Arg Cys519 mutation arose independently in at least two of the three known affected families. The presence of both mutant and normal alleles of Col2A1 in cDNA derived from cartilage obtained from this patient suggests that Cys519-containing type II collagen may continue to be produced even in advanced stages of osteoarthritis. PMID- 8507191 TI - Glucose-induced cycles of insulin release can be resolved into distinct periods of secretory activity. AB - The periodic behaviour of glucose-stimulated insulin release was studied using islets isolated from ob/ob-mice and rats. A single islet was perifused at a rate of 150 microliters/min and insulin measured in samples of the medium taken at intervals as short as 3 s. Exposure to 11 mM glucose resulted in intermittent insulin release, implying that previously observed 2-3 min cycles of secretion could be resolved into regularly occurring fast (< 25 s) transients. A further raise of glucose to 20 mM was associated with increase of the amplitudes of the transients leaving their frequencies unaffected. The discovery of the insulin transients raises the question whether there is a quantal release of the hormone in response to glucose-induced rapid oscillations of cytoplasmic Ca2+ in the pancreatic beta-cells. PMID- 8507192 TI - Physical characteristics of a factor related to the c-myc/insulin promoter binding protein ZF87/Pur-1. AB - The ZF87/Pur-1 factor is a zinc finger containing protein that binds to sites within the c-myc and insulin promoters. The open reading frame of the mRNA predicts a 49 kd protein which migrates as a 58 kd protein by SDS-PAGE. Antiserum to ZF87/Pur-1 recognizes the 58 kd protein in western blots of Hela cell nuclear extracts. The antiserum also specifically recognizes an 87 kd protein (p87) that is distributed between cytosolic and nuclear extracts. p87 found in cytosolic extracts sediments faster in a glycerol gradient than that found in nuclear extracts. These data indicate that p87 may associate with specific factors or undergo a post-translational modification that changes its conformation. PMID- 8507193 TI - 1H NMR spectroscopic studies of lipid extracts from human fatty liver. AB - Lipid extracts of biopsy samples from normal and non-alcohol-induced fatty human liver were studied by 1H-NMR at 200 MHz. Spectra of the lipid extracts from 10 mg samples were obtained in 6 min with routine acquisition parameters and allowed the calculation of the phosphatidylcholine to total fatty acyl chain ratio, the cholesterol to total fatty acyl chain ratio, the average fatty acyl chain length, the unsaturation ratio and the acylated glycerol to total fatty acyl chain ratio. The data suggest that lipids with a higher ratio of de novo synthesized fatty acyl chains are stored in non-alcohol-induced fatty liver. NMR lipid analysis appears to be a reliable method for the rapid assessment of hepatic lipid composition on bioptic specimens. PMID- 8507194 TI - Site-directed mutagenesis of the target arginine for ADP-ribosylation of nitrogenase component II in Rhodobacter capsulatus. AB - The role of the conserved residue arginine-102 in the functioning and the regulation of the nitrogenase component II protein in Rhodobacter capsulatus has been studied by site-directed mutagenesis. The arginine at position 102 was replaced by thirteen different amino acids, and the effect of these substitutions on diazotrophic growth, in vivo and in vitro nitrogenase activity, and ADP ribosylation of the component II protein was tested. The results show that although arginine is the optimal amino acid at this position, it is not essential for activity. However, the mutant proteins were not modified by ADP-ribosylation, either in the dark or after addition of NH4+, consistent with the specificity of the post-translational regulatory mechanism for the Arg-102. Indirect evidence suggest that this residue may be involved in interaction with the in vivo low potential electron donor. PMID- 8507196 TI - Low density lipoprotein subfractions increase thromboxane formation in endothelial cells. AB - Correlations between dyslipidemia and high blood pressure have been shown. It is unclear whether there is a causal relationship but there are indications that blood lipids might have a direct effect on mechanisms regulating the vascular tone. As secretory products of endothelial cells (EC) have been suggested to be involved in blood pressure regulation, we studied the influence of low density lipoprotein subfractions on thromboxane (T) synthesis in human umbilical vein endothelial cells (HUVEC). LDL can be separated into at least three major subfractions. In the present study, subfractions LDL1 (d = 1.030-1.033 g/ml), LDL 2 (d = 1.033-1.040 g/ml), and LDL 3 (d = 1.040-1.045 g/ml) were obtained by density gradient ultracentrifugation. T was measured by a radioimmuno-assay. LDL subfractions induced a dose dependent (10-100 micrograms/ml) increase in T synthesis. Control T concentration was 96 +/- 12 pg/ml. LDL 3 (205 +/- 17 pg/ml, p < 0.01) and LDL 2 (194 +/- 13 pg/ml, p < 0.05) caused a significantly higher T concentration compared to the LDL 1 subfraction (152 +/- 11 pg/ml). These results indicate that LDL 2 and 3- the subfractions with the higher density-might have a more pronounced effect on T synthesis by EC than the other LDL subfractions. PMID- 8507195 TI - Expression and activity of pre-dianthin 30 and dianthin 30. AB - Dianthin 30 is a ribosome inactivating protein (RIP 1) found in different tissues of the carnation (Dianthus caryophyllus). Recently we have isolated and sequenced a cDNA clone from a lambda gt11 expression library [Legname et al. (1991) Biochim. Biophys. Acta 1090, 119-122]. Here we describe specific PCR amplifications of either the full length pre-dianthin 30 or dianthin 30, the mature polypeptide lacking the 23 amino acid signal peptide. In vitro expression of both proteins in reticulocyte lysate generated products of the expected molecular weight. Moreover, the activity of both proteins has been evaluated confirming the characteristics of the natural product. A first attempt to produce recombinant dianthin 30 in Escherichia coli is described. PMID- 8507197 TI - Identification of a fourth angiotensin AT1 receptor subtype in rat. AB - Angiotensin II is a major regulator of cardiovascular function, fluid homeostasis and also plays a role in long-term cardiovascular disease processes. At present it is unclear if and how the diverse functions of angiotensin II may relate to different cellular receptors for this vasoactive peptide. In order to identify subtypes of angiotensin receptors we used a PCR-mediated cloning approach. Oligonucleotide sequences for PCR amplification of angiotensin receptors were selected on the basis of nucleotide sequences conserved between species. Since the coding regions of AT1-type receptors appear to be located on a single exon, we used genomic DNA as a template in the PCR reactions. Resulting amplification products represented a mixture of four different sequences as assessed by T tracking and sequencing of the partial clones. Three of the clones encode for sequences already known, whereas the fourth clone encoded a novel receptor subtype which we have termed AT1C. Deduced amino acid sequences of the four different receptor subtypes are highly homologous. The AT1C receptor nucleotide sequence homology was greatest to the described AT3 receptor (95%) and less so to the published AT1A (90%) and AT1B (82%) receptor subtypes. The variety and tissue specific expression of AT1 receptor subtypes and coexpression of different receptor subtypes may account for the diverse tissue- specific actions of angiotensin. PMID- 8507198 TI - Rat cortical and trabecular bone collagen glycosylation are differently influenced by ovariectomy. AB - This study sought to evaluate whether estrogen depletion influences the hydroxylysine glycosydes content of rat bone collagen. For this reason thirty 100 day old female rats were divided in 6 groups of 5 rats each. Three groups were ovariectomized and 3 groups were sham-operated. The animals were sacrificed at 115, 130 and 145 days of age (i.e., 15, 30 and 45 days after surgery). Cortical and trabecular bone was prepared from tibiae and femurs. Hydroxylysine glycosydes content was measured by HPLC. Ovariectomy is followed, in the rat, by an increased hydroxylysine glycosylation in trabecular bone but by a constant or slightly decreased hydroxylysine glycosylation in the cortical bone. In view of the different effects of estrogens on the two bone compartments previously reported, a possible functional explanation of these findings is proposed. PMID- 8507199 TI - Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system. AB - Glucose is the major energy source for brain tissue. It is now well established that glucose crosses the blood-brain barrier by facilitated diffusion mediated by the erythrocyte-type (GLUT 1) glucose transporter. Northern blot analysis has indicated that brain tissue expresses two different glucose transporters, the erythrocyte-type transporter and the brain-type transporter (GLUT 3). Here we use a panel of antibodies specific for four glucose transporters to examine the distribution of these transporters in various regions of rat brain and central nervous system. We show that GLUT 1 and GLUT 3 are expressed in virtually all regions of the brain examined, but that the relative levels of the proteins differ. We also demonstrate that GLUT 2 appears to be widely expressed in all brain regions, but at apparently low levels. In addition, GLUT 4 is expressed in the pituitary, the hypothalamus and the medulla. These results are discussed in the light of potential glucose-regulated processes in the brain. PMID- 8507200 TI - Midkine is a mediator of retinoic acid induced neuronal differentiation of embryonal carcinoma cells. AB - Midkine (MK) is a novel growth factor and is the product of a retinoic acid responsive gene. When P19 murine embryonal carcinoma (EC) cells were exposed to MK, they differentiated into neurons, and the neuronal differentiation was accompanied by expression of choline acetyltransferase activity. Synthesis and release of MK in the EC cells treated with retinoic acid were shown by Western blot analysis, and rabbit anti-MK antibody attenuated the action of retinoic acid to induce the neuronal differentiation. These results indicate that MK is one of the mediators of retinoic acid action to induce the neuronal differentiation in EC cells. PMID- 8507201 TI - Convenient plasmid for extrachromosomal DNA recombination in mouse cells. AB - We constructed a convenient plasmid for DNA recombination assay. The plasmid, pMR1, contains a double prokaryotic terminator to decrease the background and two unique restriction enzyme sites on both sides of the double terminator to allow for easy construction. The assay is capable of selecting the bacterial cells containing recombined plasmid DNA on a selective plate containing ampicillin and chloramphenicol. We adapted pMR1 for V(D)J recombination and homologous recombination and detected both types of recombination in murine PreB cell line. As pMR1 has the double terminator, background on the selective plate decreases effectively and we select only the recombined clones. We consider the vector, pMR1, to be convenient for the analysis of homologous and non-homologous recombinations. PMID- 8507202 TI - Molecular cloning of full-length glutamic acid decarboxylase 67 from human pancreas and islets. AB - Glutamic acid decarboxylase (GAD) is a pancreatic islet autoantigen in insulin dependent diabetes (IDD). Two forms of GAD, GAD65 and GAD67, have been identified in brain but human islets have been reported to express only GAD65. We have isolated full length GAD67 cDNA by polymerase chain reaction (PCR) cloning from human pancreas. Sequence analysis reveals only four nucleotide differences between human pancreas and brain GAD67, two of which result in amino acid changes. These differences are probably individual-specific and reflect allelic variation. Using mRNA from isolated human islets a partial sequence was obtained by PCR cloning that was identical to the midregion of pancreas GAD67 cDNA. GAD67 has previously been shown to be a target of both autoantibodies and autoreactive T cells in IDD. The presence of GAD67 in human pancreas implies that this form of GAD, as well as GAD65, has a pathogenic role in IDD. PMID- 8507203 TI - Cloning and expression of large isoform of glutamic acid decarboxylase from human pancreatic islet. AB - Glutamic acid decarboxylase (GAD) catalyzes formation of gamma-aminobutyric acid from glutamic acid and is a major autoantigen in insulin-dependent diabetes mellitus. Its two isoforms, GAD65 and GAD67, are encoded by two separate genes. We prepared human islet cDNA library and screened it with cDNA probes of rat brain GAD67. We cloned the cDNA for GAD67, the large isoform of glutamic acid decarboxylase, and determined its nucleotide sequence. Sequencing of the resulting clone identified a 1,785 residue open-reading frame encoded a 594 amino acid polypeptide that showed a 99.4% similarity with GAD67 from human brain. The bacterially expressed human islet GAD67 protein was enzymatically active and immunoreactive. The isolation of cDNA for this additional islet GAD isoforms will be important in studying the etiology and pathogenesis of IDDM. PMID- 8507204 TI - The transcriptional regulation of the growth hormone gene is conserved in vertebrate evolution. AB - Growth hormone (GH) gene expression in mammals is regulated by the interaction of the transcription factor Pit-1 with two binding sites within the proximal promoter. Four sequences, homologous to the mammalian Pit-1 motif occur in the rainbow trout (Oncorhynchus mykiss) GHII (rtGH) gene promoter, two of which partly overlap. The three regions containing these putative Pit-1 binding sequences were protected from deoxyribonuclease I digestion by nuclear extracts of GC cells, a rat pituitary tumor cell line producing Pit-1. In gel shift assays, nuclear proteins from GC cells and from trout pituitaries were found to interact specifically with one of these protected sites. Transfection experiments showed that the rtGH promoter is transcriptionally active in GC cells, the response being strongly enhanced in the presence of a cAMP analogue. The results demonstrate that rat Pit-1 binds to and activates the rtGH promoter, indicating that the basic mechanisms regulating GH gene transcription have been conserved between fish and mammals. PMID- 8507205 TI - The catalytic activity of four expressed human cytochrome P450s towards benzo[a]pyrene and the isomers of its proximate carcinogen. AB - The catalytic properties of expressed human cytochromes P4501A1, 1A2, 3A4 and 3A5 with respect to the metabolite distribution for the carcinogen benzo[a]pyrene (BP) and the proximate carcinogen (-)-trans-7,8-dihydroxy-7,8 dihydrobenzo[a]pyrene ((-)-BP-7,8-DHD) were determined. P4501A1 formed a higher proportion of the proximate carcinogen from BP than the other isozymes. Both P4501A1 and 1A2 were more selective for oxidation at the benzo ring of BP and showed a greater production of dihydrodiol metabolites than either P4503A4 or 3A5. The formation of diolepoxides from the individual enantiomers of BP-7,8-DHD occurred in a highly stereoselective fashion. PMID- 8507206 TI - Phosphorylation of NF-I in vitro by cdc2 kinase. AB - Nuclear factor I (NF-I) was purified to near homogeneity from Ehrlich ascites tumor cells. Mouse NF-I consisted of two peptides with relative molecular masses of 53 and 55 kDa and bound to the authentic NF-I site of the adenovirus DNA with no significant affinity with the CCAAT box. The purified protein was efficiently phosphorylated in a reaction containing immunoprecipitates with an anti-cdc2 kinase antibody. This phosphorylation was abolished when a synthetic peptide containing the consensus phosphorylation site by cdc2 kinase was added in excess to the reaction. These findings indicate that mouse NF-I is phosphorylated in vitro by the cdc2 protein kinase. PMID- 8507207 TI - Underwinding of DNA on binding of yeast TFIID to the TATA element. AB - The TATA box-binding factor TFIID is an essential component for the initiation of transcription by eukaryotic RNA polymerase II. We investigated the effect of DNA supercoiling on TFIID: promoter interactions using recombinant yeast (ry) TFIID. DNase I footprinting analysis showed that ryTFIID has a higher affinity for the adenovirus major late promoter in the negatively supercoiled state than that in the relaxed state. On the contrary, its affinity for the Drosophila hsp70 promoter is constant irrespective of DNA topology. Binding of ryTFIID to these promoters induced underwinding of duplex DNA. The functional TATA box and active ryTFIID are essential for the underwinding. The step was facilitated by negative supercoiling of DNA on the adenovirus major late promoter but not on the Drosophila hsp70 promoter. PMID- 8507208 TI - Catalytic polyclonal antibodies. AB - The production and characterization of rabbit polyclonal antibodies that catalyze the hydrolysis of trityl protecting groups is described. The catalytic activity increased throughout the immunization regimen, exhibiting a later and steeper rise than the simple hapten-specific antibody titer. The catalytic polyclonal antibodies displayed saturation behavior, consistent with classic Michaelis Menton kinetics. An apparent catalytic rate enhancement (kcat/kuncat) of 125 and a Km of 31 microM were measured for the polyclonal sample. Inhibition studies indicated that 12% of the antibodies either binds the hapten or is a catalyst. Analyzing polyclonal antibodies for catalytic activity is proposed as a substantially faster, more cost effective and more general way to screen new hapten designs for their relative abilities to produce antibodies with catalytic activity. PMID- 8507209 TI - In vitro translation of the human insulin proreceptor results in N-linked glycosylation without dimer formation. AB - The heterotetrameric configuration of the cell surface human insulin receptor (hINSR) is important for mediating insulin action. Investigation of proreceptor dimerization, the quaternary processing event during biogenesis, offers the potential to examine interactions between disulfide-linked receptor subunits. Thus, dimer formation of the proreceptor was examined in a cell-free system that utilized a coupled transcription and translation method with rabbit reticulocyte lysate. Translation products were labeled with [35S]methionine and identified by non-reducing SDS-polyacrylamide gel electrophoresis and autoradiography. In vitro synthesis in the presence of oxidized glutathione failed to demonstrate dimerization of the nascent proreceptor. Co-translational processing with the addition of microsomal membranes resulted in N-linked glycosylation of the proreceptor but without dimer formation. Thus, similar to that observed in vivo, insulin proreceptor dimerization does not appear to be a co-translational or early post-translational event. PMID- 8507210 TI - Processing of the small GTP-binding protein SpYPT1p in Schizosaccharomyces pombe and in mammalian COS cells. AB - SpYPT1p belongs to a family of ras-like GTP-binding proteins which is believed to be involved in the regulation of intracellular vesicular trafficking. We have analyzed the processing of this protein in its natural environment, the fission yeast Schizosaccharomyces pombe, and when expressed in transfected mammalian COS cells. In COS cells SpYPT1p exists in two forms: a cytosolic 24 kDa protein which represents the unprocessed precursor form and a prenylated 23.5 kDa protein which is equally distributed between membranes and cytosol. In contrast, in S.pombe we have been unable to detect any prenylation of the protein, despite the presence of a potential C-terminal CysCys prenylation site. In addition a 23.5 kDa form was localized exclusively in the cytosol and a third membrane-bound 23 kDa form was also detected. Pulse-chase experiments revealed that in S.pombe SpYPT1p is co translationally or immediately after translation converted to the 23.5 kDa form which is then rapidly processed to the 23 kDa membrane bound form. We have been unable to detect any significant soluble pool of the protein. PMID- 8507211 TI - X-ray diffraction studies of fibrils formed from peptide fragments of transthyretin. AB - Two synthetic peptide fragments of the plasma protein transthyretin (TTR), previously shown to form fibrillar structures in vitro, have been examined using electron microscopy and X-ray diffraction. The fibrils displayed all characteristics of cross beta-sheet conformation with antiparallel strand spacing of 4.7 A and intersheet spacings of 8-10 A as well as reflections indicating further lateral repeating units. A third peptide containing a substitution equivalent to a mutation in TTR known to increase the propensity of TTR to form amyloid was also examined. It also formed fibrils and showed similar cross beta sheet structure, but with closer intersheet packing than its native equivalent. PMID- 8507212 TI - Expressions of matrilysin and stromelysin in human glioma cells. AB - Production of matrilysin and stromelysin by five human glioma cell lines was investigated by Northern blot and immunoblot analyses. Four cell lines constitutively produced matrilysin. Its production was stimulated by phorbol-12 myristate-13-acetate (PMA) in two cell lines and by transforming growth factor beta 1 (TGF-beta 1) in two other cell lines. Stromelysin transcript was constitutively expressed in only two cell lines, but enhanced or induced by PMA in four cell lines. These results suggest that these enzymes, especially matrilysin, may be involved in the invasive growth of neoplastic glial cells. PMID- 8507213 TI - The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. AB - OBJECTIVE: To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. METHODS: We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. RESULTS: The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count). The committee also proposes specific ways of measuring each outcome. CONCLUSION: We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies. PMID- 8507214 TI - An organizational model for developing multidisciplinary clinical research in the academic medical center. AB - OBJECTIVE: To assess the impact of a new organizational model designed to stimulate multidisciplinary clinical research. METHODS: We conducted a prospective, 3 1/2-year followup of a research training program for residents, fellows, faculty, nurses, and allied health professionals in rheumatology and orthopedic surgery. Program components included a multidisciplinary clinical research conference, a clinical research methods curriculum, consultations, a patient registry, and regular meetings of a Research Methodology Core group. Measures included participation in each program component and the number of new investigators who developed funded clinical research projects. RESULTS: The multidisciplinary clinical research conference was attended by 369 new health professionals; 218 professionals participated in at least one of the courses; and 280 consultations were provided to 108 professionals. Thirteen new investigators developed 17 new grant proposals, of which 14 were externally funded. Investigators who successfully procured funding for new projects demonstrated significantly more participation in program components compared with those who did not (P < 0.001 overall). CONCLUSION: Participation in the program was significantly correlated with the development of new prospective patient-based studies. We conclude that our model has the potential to foster such research in other settings. PMID- 8507215 TI - Quality of life issues in women with vertebral fractures due to osteoporosis. AB - OBJECTIVE: To learn about the physical, emotional, and social limitations experienced by postmenopausal women who have back pain due to vertebral fractures resulting from osteoporosis. METHODS: We conducted a cross-sectional survey of female patients with persistent pain due to vertebral fractures. RESULTS: Respondents had a mean (+/- SD) bone density of 0.87 +/- 0.13 gm/cm2 and a mean (+/- SD) of 2.84 +/- 2.18 fractures. Disability was identified in pain, movement, activities of daily living, and emotion. There was a poor correlation between quality of life and findings on radiography or densitometry. CONCLUSION: To evaluate the effects of osteoporosis on a patient's functional status, direct questioning is required. PMID- 8507216 TI - Pathogenesis of giant cell arteritis. PMID- 8507217 TI - Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. Regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor. AB - OBJECTIVE: To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). METHODS: MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. RESULTS: High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast-like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin-1 (IL-1) and tumor necrosis factor in vitro. IL-1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. CONCLUSION: Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints. PMID- 8507218 TI - Stimulation of the secretion of latent cysteine proteinase activity by tumor necrosis factor alpha and interleukin-1. AB - OBJECTIVE: Cultured synovial fibroblast-like cells from 3 patients with rheumatoid arthritis (RA) and 3 patients with osteoarthritis (OA) were evaluated for their potential to secrete cysteine proteinases spontaneously and after stimulation by tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1). METHODS: Culture media and cell lysates were analyzed before and after high performance liquid chromatography (HPLC) using the enzymatic substrate, Z-Phe-Arg AMC, and by immunoblotting with anti-cathepsin B antiserum. Immunolocalization of cathepsin B was studied on cell monolayers. RESULTS: Latent cysteine proteinase activity was found to be secreted spontaneously by cultured synovial fibroblast like cells. This activity was increased after treatment with either TNF alpha or IL-1. Stimulated protease activity was eluted by HPLC at a peak coincident with that of purified cathepsin B. By immunoblot, cell supernatants contained a 43-kd form of cathepsin B, while cell lysates contained a 30-kd form, consistent, respectively, with cathepsin B before and after cleavage of its propeptide. An intracellular increase in cathepsin B after treatment with TNF alpha was also seen with immunohistochemical studies. CONCLUSION: TNF alpha (in the 6 cases studied) and IL-1 (in 4 cases) stimulated the secretion of a latent cysteine proteinase activity from synovial fibroblast-like cells, which appears to represent primarily cathepsin B. PMID- 8507219 TI - Levels of synovial fluid interleukin-1 receptor antagonist in rheumatoid arthritis and other arthropathies. Potential contribution from synovial fluid neutrophils. AB - OBJECTIVE: To measure synovial fluid (SF) levels of interleukin-1 receptor antagonist (IL-1ra) and to determine the capacity of SF neutrophils (PMN) to synthesize and release IL-1ra. METHODS: A sensitive and specific enzyme-linked immunosorbent assay was used to measure SF IL-1ra protein concentrations and IL 1ra production by isolated SF PMN: RESULTS: SF IL-1ra levels were elevated in 13 of 16 samples from patients with rheumatoid arthritis (RA) (mean 17.1 ng/ml), in 6 of 18 samples from patients with infectious or inflammatory, non-RA arthropathies (mean 10.6 ng/ml), and in none of 11 noninflammatory SF samples. SF IL-1ra levels correlated with SF PMN concentrations (r = 0.680, P < 0.00001). Isolated SF PMN contained preexisting IL-1ra protein in the absence of messenger RNA (mRNA). In addition, both lipopolysaccharide and granulocyte-macrophage colony-stimulating factor induced modest increases in IL-1ra mRNA by cultured SF PMN. CONCLUSION: IL-1ra levels are increased in > 80% of RA SF samples. SF PMN produce IL-1ra, possibly contributing to the levels of IL-1ra present within the SF. PMID- 8507220 TI - Production of leukemia inhibitory factor by human articular chondrocytes and cartilage in response to interleukin-1 and tumor necrosis factor alpha. AB - OBJECTIVE: To investigate the production of leukemia inhibitory factor (LIF) by human articular chondrocytes and cartilage. METHODS: Chondrocytes and cartilage were cultured with and without added cytokines, and the conditioned media assayed for LIF by a specific radioreceptor competition assay. RESULTS: Interleukin-1 (IL 1) and tumor necrosis factor alpha (TNF alpha) stimulated LIF production by chondrocyte monolayers and cartilage. LIF was generally not detected in unstimulated cultures. Northern blot analysis showed increased amounts of LIF messenger RNA in IL-1- and TNF alpha-treated chondrocyte cultures. CONCLUSION: Chondrocytes, stimulated by IL-1 and/or TNF alpha, are potential contributors to the elevated levels of LIF observed in the synovial fluids of patients with rheumatoid arthritis and other inflammatory arthritides. PMID- 8507221 TI - Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo controlled trial. AB - OBJECTIVE: To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate. METHODS: We conducted a multicenter randomized, double-blind, placebo-controlled trial of leucovorin administration, 2.5-5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups. RESULTS: Ninety-two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty-two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%, P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups. CONCLUSION: The methotrexate-leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy. PMID- 8507222 TI - Differential effects of diclofenac and aspirin on serum glutamic oxaloacetic transaminase elevations in patients with rheumatoid arthritis and osteoarthritis. AB - OBJECTIVE: To examine elevations in levels of serum glutamic oxaloacetic transaminase (SGOT) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) taking placebo, aspirin, or diclofenac, and to seek possible explanations for the occurrence of these elevations. METHODS: We conducted a meta-analysis of individual case reports from 3 RA protocols and 5 OA protocols, encompassing 814 diclofenac-treated patients, 443 aspirin-treated patients, and 359 placebo treated patients. All of the RA protocols had nearly identical inclusion and exclusion criteria, as well as safety studies and followup; the same was true for the OA protocols. Analysis included correlation analysis and multiple linear and logistic regression, accounting for numerous potential confounding variables, with the SGOT as the dependent variable. F tests were used for hypothesis testing. RESULTS: By several analytic approaches, the principal determinants of SGOT concentrations were found to be baseline SGOT value, the use of aspirin in RA patients, and the use of diclofenac in OA patients. Other significant factors contributing to an increase in SGOT concentrations were duration of therapy and, perhaps, daily dosage (mg/lb). Hypothesis testing supported these results. Given a statistically average patient, we predicted a 1-2% chance of a mildly elevated SGOT level occurring among placebo-treated patients, a 6-7% chance among diclofenac- or aspirin-treated patients with RA, a 12% chance among diclofenac treated patients with OA, and a 2% chance among aspirin-treated patients with OA. CONCLUSION: This study demonstrates a powerful method for performing meta analysis, using available individual patient data to examine numerous factors that may affect an outcome of interest. In this case, mild elevations of SGOT were examined and found to be related to baseline SGOT levels, diclofenac use (in OA), and aspirin use (in RA). Of numerous other potential factors examined, including age, sex, alcohol use, concomitant medications, and concomitant diagnoses, only duration of therapy and, to a small extent, daily dosage, were also consistent determinants of SGOT elevation. The SGOT elevations were minimal and were not related to the occurrence of clinical hepatitis: No clinical hepatitis occurred. PMID- 8507223 TI - Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish population. AB - OBJECTIVE: To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population. METHODS: We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain. RESULTS: A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both Dw10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the "shared epitope" hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15-DQ8 (DRB1*0405 DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). CONCLUSION: Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations. PMID- 8507224 TI - Association of HLA-DR and HLA-DQ antigens with congenital dislocation and dysplastic osteoarthritis of the hip joints in Japanese people. AB - OBJECTIVE: To investigate the frequency of HLA-DR and DQ antigens among patients with congenital dislocation of the hip joint or dysplastic osteoarthritis (OA) and to determine whether tissue typing might contribute to better understanding of these disorders. METHODS: HLA-DR and DQ typing was undertaken in 18 patients with congenital dislocation of the hip joints, 65 patients with dysplastic OA of the hip, 42 patients with primary OA of the knee, and 40 normal controls. Typing for HLA-D antigens was performed using the standard microlymphocytotoxicity method. RESULTS: The frequency of HLA-DR4 in patients with congenital dislocation of the hip joint (61.1%) and patients with dysplastic OA of the hip (58.5%) was significantly increased compared with normal controls (27.5%) (Pcorr < 0.05 and P < 0.01, respectively). The relative risk for HLA-DR4 was 4.1428 and 3.7104, respectively, in these 2 disease groups. The frequency of HLA-DR4 in the patients with primary OA of the knee (35.7%) did not differ significantly from that in normal controls. CONCLUSION: The results strongly indicate that development of congenital dislocation of the hip joint and progression of dysplastic OA of the hip are associated with genes of the HLA-D region. PMID- 8507225 TI - Elevated synovial fluid levels of interleukin-6 and tumor necrosis factor associated with early experimental canine osteoarthritis. AB - OBJECTIVE: To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) from the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA. METHODS: OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF from the operated and contralateral (control) knee joints was assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured. RESULTS: IL-6 levels in SF from the operated joint compared with the control joint were significantly elevated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no significant difference in the concentration of APMA-activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but there was no correlation with the levels of TNF or GAG. CONCLUSION: This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL-6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury. PMID- 8507226 TI - Autoantibodies to chromatin components in juvenile rheumatoid arthritis. AB - OBJECTIVE: To characterize autoantibodies to chromatin components in patients with juvenile rheumatoid arthritis (JRA). METHODS: The sera of 50 children with JRA were analyzed for antinuclear antibodies (ANA) by immunofluorescence and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: By immunofluorescence, ANA and antibodies to high-mobility group proteins or to DNA free histones were common in patients with pauciarticular JRA and rheumatoid factor-positive polyarticular JRA. However, reactivity with histone-DNA complexes was rare. CONCLUSION: Because antihistone antibodies detected by ELISA failed to bind chromatin or other histone-DNA complexes, they are not likely to represent the immunofluorescent ANA activity in serum. PMID- 8507227 TI - Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis. AB - OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods. PMID- 8507228 TI - Bilateral tumoral infiltration of the Achilles tendons revealing chronic myelomonocytic leukemia. AB - Extrahematologic manifestations, such as symptoms of rheumatic disease, have been recorded in association with myelodysplastic syndromes, including chronic myelomonocytic leukemia (CMML). We report the case of a 51-year-old woman with tumoral infiltration of the Achilles tendons bilaterally, indicating CMML. This diagnosis was confirmed at postmortem examination. PMID- 8507229 TI - Synovitis of the knee in a 42-year-old man. PMID- 8507230 TI - A young woman with a photosensitive butterfly facial rash, fatigue, anemia, and positive antinuclear antibody. PMID- 8507231 TI - Sicca syndrome associated with human immunodeficiency virus infection: an immunohistochemical study. PMID- 8507232 TI - Derivation of the SLEDAI. PMID- 8507233 TI - The lack of futility in screening for prostate cancer. PMID- 8507234 TI - Two support "up front" fees. PMID- 8507235 TI - Teaching the teachers. PMID- 8507236 TI - Child resistant containers needed for liquid medications. PMID- 8507237 TI - Secretory pathway components: targets for autoimmunity? PMID- 8507238 TI - Restricted TCR repertoire and disease. PMID- 8507239 TI - Rhabdomyosarcoma of the orbit. PMID- 8507240 TI - Vibrio parahaemolyticus septicemia associated with water-skiing. PMID- 8507241 TI - Nurse practitioners in accident and emergency departments. PMID- 8507242 TI - Use of problem lists in letters between hospital doctors and general practitioners. PMID- 8507243 TI - Managing depression in general practice. PMID- 8507244 TI - Meniscal cysts and tears. PMID- 8507245 TI - The phenomenon of anetoderma occurring over pilomatricomas. PMID- 8507246 TI - Psychological disorders and TMD. PMID- 8507247 TI - Fine needle aspiration. PMID- 8507248 TI - Supply of vaccines. PMID- 8507249 TI - Neonatal congenital factor X deficiency. PMID- 8507250 TI - Hot pulp syndrome. PMID- 8507251 TI - Adieu, tetracycline pleurodesis (but not in Germany) PMID- 8507252 TI - The Journal and SI units. PMID- 8507253 TI - Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. PMID- 8507254 TI - Hepatic myelopathy. PMID- 8507255 TI - Double labeling of syringes to prevent "drug swaps". PMID- 8507256 TI - Chloral hydrate administration to children. PMID- 8507257 TI - Epidural opioid selection. PMID- 8507258 TI - Mitomycin C after pterygium excision. PMID- 8507259 TI - Management of croup. PMID- 8507260 TI - Risk factors for acute graft-versus-host disease associated with cyclosporine and methotrexate prophylaxis. PMID- 8507261 TI - Alternative allergy and the GMC. PMID- 8507262 TI - Paget's disease of bone. PMID- 8507263 TI - HIV transmission, travel and Thailand. PMID- 8507264 TI - Quality of life measures. PMID- 8507265 TI - Treating hypertension in elderly patients. PMID- 8507266 TI - Medical education. PMID- 8507267 TI - Child resistant containers for liquid medications. PMID- 8507268 TI - Umbilical cord clamping in preterm infants. PMID- 8507269 TI - The laryngeal mask. PMID- 8507270 TI - Gestational diabetes mellitus. PMID- 8507271 TI - Processing of trephine biopsy specimens. PMID- 8507272 TI - Improving access to primary care. PMID- 8507273 TI - [In memory of the 200th anniversary of the death of Pal Bugat [corrected]. PMID- 8507274 TI - Comments on gender differences in pharmacokinetics and pharmacodynamics. PMID- 8507276 TI - Cutaneous leishmaniasis treated with controlled localized heating. PMID- 8507275 TI - Hyperkalemia from nonelectrolyte solutions. PMID- 8507278 TI - Ionescu-Shiley valve failures. PMID- 8507277 TI - Ultraviolet radiation abolishes cutaneous nerve stainings with two axon-specific antibodies in guinea-pig skin. AB - Cutaneous nerve fibers in guinea-pig skin were histochemically stained with two specific antibodies against different axonal proteins, a newly available protein gene product 9.5 and neuron-specific enolase. A semi-quantitative analysis revealed that the density of nerve fibers positive for either antibody was reversibly decreased following a single exposure to medium wave length ultraviolet (UVB) radiation and psoralen plus long wave ultraviolet (UVA) radiation (PUVA). UVA radiation alone did not markedly affect nerve fiber staining. The UVB/PUVA-induced nerve changes were augmented and prolonged following multiple exposures to UVB and PUVA. Nerve fiber staining was not altered by topical application of corticosteroids. Our findings suggest that both UVB and PUVA can alter the cutaneous innervation density. PMID- 8507279 TI - Duplex scan surveillance of infra-inguinal bypass grafts. PMID- 8507280 TI - American Academy of Pediatrics Committee on Substance Abuse and Committee on Children with Disabilities: Fetal alcohol syndrome and fetal alcohol effects. PMID- 8507281 TI - Flow cytometric analysis of ploidy in colorectal cancer: a multicentric experience. AB - Ploidy and cell proliferation determined by flow cytometry were assessed on colorectal cancers from patients admitted to two Italian cancer research centres. A total of 181 patients were followed prospectively for 4 years at the Istituto Regina Elena (IRE) of Rome and at the Istituto Nazionale Tumori (INT) of Milan. Fresh (at the IRE) or frozen (at the INT) tumour material and similar procedures were used for subsequent sample preparation. Similar frequencies of aneuploid tumours (63% vs 66%) and superimposable median DNA indices (1.6) were observed for the two case series. In both series, DNA ploidy was generally unrelated to clinico-pathological factors, except for a higher frequency of aneuploid tumours in Dukes' D (88%) than in Dukes' A stage (33%) in the IRE experience. DNA ploidy was a weak prognostic indicator at 3 years but not at 4 years in the IRE case series, and it never exhibited a clinical relevance in the INT experience. Conversely, multiploidy was an indicator of worse relapse-free and overall survival at 4 years in the IRE and INT case series. PMID- 8507282 TI - Case management in a health maintenance organization: improving quality of care. AB - 1. Given the current climate in the health care industry, the occupational health nurse can take the opportunity to formalize the case management role. 2. A unique aspect of case management within the structure of a health maintenance organization allows for effective use of existing internal services and occupational health staff. 3. In developing an occupational case management model, a framework was constructed to include the core aspects of management for all injured workers. A four level system was developed to meet the injured workers' need for the coordination of care and, when indicated, intensive case management. 4. Improved quality of care for the injured worker and a return to an optimal state of health and productivity is already being realized. Formalized evaluation will provide objective measurements of program efficacy and future planning. PMID- 8507283 TI - Knowledge of occupational hazards in photography: a pilot study. AB - 1. Artists use many materials composed of the same chemicals that cause major occupational health problems in industry. 2. The majority of artists are unaware of the potential hazards in the materials and processes they use. 3. The pilot study revealed that greater than 90% of the amateur photographers did not use safety precautions in the darkroom. 4. The most common perceived barrier to the use of safety precautions was the lack of knowledge about chemical safety. PMID- 8507284 TI - Home health care: occupational health issues. AB - 1. Although much work has been done to identify occupational risks to health care workers in institutions, little has been done to describe such risks in the growing home care industry. Changes in the nature of home care suggest the risks may be equivalent, with additional risks from the variable environment of the home. 2. Directors of home care agencies in Northern California were surveyed with respect to the nature of home care, workers, characteristics of occupational programs, and common illnesses and injuries. Musculoskeletal injuries were the most common occupational injuries reported. 3. Despite legislation and accreditation standards, occupational programs in home care agencies are incomplete. Further work is needed to determine the relationship between the presence of occupational health programs and home health care outcomes. PMID- 8507286 TI - Random drug testing: a commitment to a drug free workplace. PMID- 8507287 TI - Searching the literature. PMID- 8507285 TI - Mass colorectal cancer screening: choosing an effective strategy. AB - 1. Colorectal cancer is the third leading cause of cancer related death in the U.S. 2. Efforts to control this disease have focused primarily on early disease detection and treatment. 3. The occupational health nurse can assume the role of educating employees regarding known risk factors and disease signs and symptoms. 4. In those situations when employee risk factors justify mass screening, the occupational health nurse must work to identify the high risk individuals appropriate for screening and facilitate their understanding and compliance with screening and referral procedures. PMID- 8507288 TI - [Health effects of ultraviolet radiation]. AB - Exposure to ultraviolet radiation (UVR) occurs from both natural and artificial sources. The main natural source is the sun. On the other hand, artificial UVR sources are widely used in industry and also used in hospitals, laboratories, etc. because of their germicidal properties. They are even used for cosmetic purposes. UVR can be classified into three regions according to its wavelength: as UVA (320-400nm), UVB (320-280nm) and UVC (280-200nm). The UVC has the greatest health effect on humans among the three. The sun radiates a wide range of spectrum of electromagnetic radiation including the UVR, however the radiation below 290 nm in wavelength does not reach the surface of the earth for effective absorption by the stratospheric ozone layer. As a result, UVR from a natural source consists of only UVA and a part of UVB. On the other hand, artificial UVR sources include UVC region and have serious effects on the human body, especially on the skin and eyes. The health effects of UVR on humans can be beneficial or detrimental, depending on the amount and form of UVR, as well as on the skin type of the individual exposed. It has been acknowledged that a long period of UVR deficiency may have harmful effects on the human body, such as the development of vitamin D deficiency and rickets in children due to a disturbance in the phosphorus and calcium metabolism. Appropriate measures to increase the amount of exposure to UVR, especially to UVB radiation by the use of sun bathing, the exposure to artificial UVR sources, etc. have shown to prevent disease states caused by UVR deficiency. The harmful effects of UVR consist of erythema, sunburn, photodamage (photoaging), photocarcinogenesis, damage to the eyes, alteration of the immune system of the skin, and chemical hypersensitivity. Skin cancer is commonly produced by UVR. In this review, various states of UV from solar radiation and the degree of exposure to UVR are introduced. The benefits and harmful health effects of UVR are discussed in relation to the skin type of humans. The measures of protection from UVR, such as sunscreen preparations, protective clothing against UVR, etc. are also introduced. PMID- 8507289 TI - [Studies on development of evaluation method for wood-based floors. Part 1. Evaluating the attenuational capacity of human locomotor system due to the acceleration at several parts of the human body]. AB - Experiments were conducted to compare the impact on several parts of the body caused by the striking of the heel during human gait. In these experiments, five kinds of wood flooring that have differing levels of light weight-impact sound insulating efficiency were used. The obtained results were as follows: 1) The generated acceleration of calcaneus varied with the difference of flooring. According to the regression analysis, the open polygonal relationship between bound back coefficient of floor and acceleration of calcaneus was determined. 2) The impact force given to the calcaneus propagated from the heel to the forehead after most of the force being absorbed at the ankle and the knee. We found direct correlation between the subjective feeling of floor pliabilty and the force to the leg. Therefore, it was suggested that the measurement of the force to the ankle and the knee was important in evaluating the efficiency of floors. PMID- 8507290 TI - [Physical fitness and motor ability in obese boys 12 through 14 years of age]. AB - Excess body fat has generally been considered to be an influential factor to physical fitness and motor ability in obese boys. However, little information is available on the physical fitness and motor ability in obese boys. The purpose of this study was to clarify characteristics of physical fitness and motor ability in obese boys. The subjects were three hundreds and five boys aged 12-14 years. Nineteen physical fitness and motor ability items were tested and skinfold thickness was measured at six sites. Bioelectrical impedance was measured using a tetrapolar impedance plethysmograph (Selco SIF-891). Body density was calculated from the formula of Kim et al. The results of comparison clearly indicated that the obese group was significantly poorer in 1,500-m run, 5-min run, 50-m run, running long jump and many other variables, but was superior only in back strength. To analyze the factorial structure in boys, principal factor analysis was applied to the correlation matrix which was calculated with 19 variables, and then five factors were extracted. The obese group was significantly poorer in total body endurance and muscular endurance than the non-obese group. From these results, it was confirmed that the excess body fat could be one of the most important factors that affects the state of many physical fitness and motor ability elements in obese boys. However, the relationships between physical fitness, motor ability and the degree of fatness seem to be rather complicated. A great deal of data should be accumulated for more detailed analysis on the influence of the excess body fat in obese boys. PMID- 8507291 TI - [The effect of aerobic exercise training on internal body fat in obese women]. AB - A group of 11 obese women (from 13% of ideal weight and higher) volunteered to participate in a study designed to reduce weight in a 92-day program of aerobic exercise. Before and after the weight reduction period, body fat indices were measured by deuterium oxide (D2O) dilution and by skinfold anthropometry. Changes in internal body fat and subcutaneous fat were calculated. Mean weight loss was 3.6 +/- 1.2 kg, and internal body fat and subcutaneous fat were 1.8 +/- 1.3 kg (21.2%) and 3.0 +/- 0.9 kg (16.0%), respectively. Highly significant correlation were obtained between changes in internal body fat and total body fat (r = 0.856, p < 0.001). However, changes in internal body fat were not significantly associated with changes in waist to hip ratio (WHR). In the present study, we found that changes in total body fat were significantly related to changes in internal body fat during treatment of obesity with aerobic exercise. However, changes in internal body fat were not valid estimates of changes in body fat distribution in relation to changes in WHR. PMID- 8507292 TI - [A survey on physiological strains of asbestos abatement work wearing protective clothing in summer]. AB - Since the health hazard of asbestos fibers has been widely recognized, the number of asbestos abatement projects in schools has increased rapidly. Most of these projects were planned during summer vacation from school. However, in Japan, it is hot and humid in summer. Moreover, the workers have to wear impermeable protective clothing because of the asbestos exposure risk. The purpose of this survey is to study the workload of asbestos abatement work by measuring physiological reactions. Physiological strains of 12 male workers and working conditions during asbestos abatements work in two schools were measured in August in 1988 and in 1989. Body weight loss by the work of all workers was measured, and heart rate, rectal temperature and skin temperatures at five sites of some of them were measured every minute. In both workplaces, the workers wore disposable coveralls with hoods and shoes covers and protective masks. Air temperature in the workplaces was between 24.6 degrees C and 28.8 degrees C, and air humidity was between 85% and 96%. The high humidity was result of covering the floor, ceiling and wall of the workplaces were covered with vinyl seats, and sprinkling the asbestos fibers with water to lower the amount of asbestos in the air. Working hours of asbestos abatement were between 46 minutes and 95 minutes. Sweat rates were between 217 g/h and 605 g/h. These values were greater compared to the estimate values when work was done wearing commonly used light clothing. Heart rates during asbestos abatement work did not exceed 150 beats/min in one school where the temperature was 25 degrees C-27 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507293 TI - [Hyperbaric physiology of apnoea deep diving (I)]. PMID- 8507294 TI - A man of courage. PMID- 8507295 TI - Residential care at its best: the Bowers Home. PMID- 8507296 TI - An ordinary but special touch. PMID- 8507297 TI - High touch/high tech. PMID- 8507298 TI - The effect of caring touch on the psychological well-being of selected residents of a long-term care facility. AB - This study examined the effect of caring touch on the psychological well-being of selected residents of a long-term care facility in suburban South Carolina. Using a quasi-experimental design of pre-test and post-test, with experimental and control groups, Bradburn's Affect-Balance Scale (ABS) was used to measure well being in 19 people, nine of whom received two interventions of hand massage. Paired and two-sample t-tests were used to examine groups means and difference scores. Subjective data indicated positive responses to touch, although no statistically significant improvement in ABS scores occurred, suggesting a need for design and outcome measurement changes. PMID- 8507299 TI - The touching goes both ways. PMID- 8507300 TI - In memoriam Professor Paul Mandel. PMID- 8507301 TI - General cortical involvement in a late-onset case of Alzheimer disease. A biochemical approach by quantitation of abnormal tau proteins. AB - We have performed a biochemical mapping of the neurofibrillary degeneration in all cortical areas of Alzheimer patients, using the immunological quantification of pathological tau 55, 64, and 69. These abnormally phosphorylated proteins, which are the basic components of PHF, are reliable markers of the degenerating process in Alzheimer disease. Here, we report our biochemical findings on a brain from a 90-yr-old woman with an 8-yr history of Alzheimer disease who exhibited dramatic and general cortical involvement. The detection of these markers was very high in all Brodmann areas, even in primary motor, somatosensory, or visual cortex. This case report contrasts with other studies, which suggested that a more virulent disease process is generally associated with an early onset and argues for the heterogeneity of the disease. Moreover, we show here that the immunodetection of abnormal tau proteins using the western blot method is a precise, reliable, and reproducible way to quantify the degenerating process in AD. PMID- 8507302 TI - Effect of acrylamide on the distribution of microtubule-associated proteins (MAP1 and MAP2) in selected regions of rat brain. AB - The effect of acrylamide treatment on the immunocytochemical localization of microtubule-associated proteins (MAP1 and MAP2) was studied in different brain regions (cerebellum, cerebral cortex, and hippocampus) of adult rats. Animals were treated with acrylamide (estimated mean dose: 15 mg/kg/d) orally for 2 wk when they showed slight hindlimb weakness. Immunoreactivity for MAP1 and MAP2 was detected in tissue sections with monoclonal antibodies according to the Sternberger's peroxidase-antiperoxidase technique. Intense MAP1 immunoreactivity was observed in neuronal perikarya and dendrites, with faint staining in axons. By contrast, MAP2 immunostaining was selectively observed in dendrites and neuronal perikarya. Treatment of animals with acrylamide reduced immunoreactivity for both MAP1 and MAP2 in hippocampus and cerebellum, with relatively little change in cerebral cortex. Loss of MAPs immunoreactivity in affected brain areas likely proceeded from dendrite to perikaryon. The results of this study indicate that hippocampal compromise is part of the neurotoxic picture associated with rodent exposure to acrylamide. PMID- 8507303 TI - Hypothermia blunts acetylcholine increase in CSF of traumatically brain injured rats. AB - Activation of muscarinic acetylcholine (ACh) receptors contributes to the pathophysiological consequences of moderate experimental traumatic brain injury (TBI). Hypothermia (30 degrees C) provides protection in experimental TBI. We measured ACh levels in CSF and plasma 5 min after moderate fluid percussion TBI under normothermic or hypothermic conditions, because ACh in the CSF has been correlated with the severity of behavioral deficits after TBI. Three groups were examined: TBI with hypothermic brain (30 degrees C), TBI with normothermic brain (37 degrees C), or sham TBI with normothermic brain (37 degrees C). ACh concentrations in CSF were significantly higher in 37 degrees C TBI rats, but not in 30 degrees C TBI rats compared to shams. ACh concentrations in plasma did not differ between groups. These results suggest that a contributing factor to the neuroprotective effects of moderate hypothermia in TBI may be related to the reduction of excessive ACh levels in the central nervous system following injury. PMID- 8507304 TI - Changes in the cytoplasmic (lactate dehydrogenase) and plasma membrane (acetylcholinesterase) marker enzymes in the synaptic and nonsynaptic mitochondria derived from rats with moderate hyperammonemia. AB - The activities of the cytoplasmic and plasma membrane marker enzymes: lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), respectively, were measured in the cerebral homogenates, in the synaptic and nonsynaptic mitochondrial fractions, and in the postmitochondrial supernatants derived from rats in which a 3-d, moderately hyperammonemic condition (no more than 120% increases in blood ammonia) was produced by repeated administration of ammonium acetate (simple hyperammonemia, SHA) or a hepatotoxin, thioacetamide (TAA) (hepatic encephalopathy, HE). As measured in the homogenate and postmitochondrial supernatants, neither of the enzyme activities was affected by SHA or HE. SHA and HE increased the synaptic mitochondrial LDH activity by respectively 53 and 24%, but reduced this enzyme activity in nonsynaptic mitochondria by 19%. Both conditions stimulated the synaptic and nonsynaptic mitochondrial AChE activity by 30-40%. By contrast, the only significant change produced in these fractions by in vitro treatment with a toxic (3 mM) concentration of ammonium chloride was a slight decrease of LDH activity in nonsynaptic mitochondria and postmitochondrial supernatants. It is concluded that moderate hyperammonemia modifies subsequent separation of both cerebral classes of mitochondria from the cytosolic and plasma membrane components. This modification is likely to reflect subtle hyperammonemia related changes in the physicochemical properties of the two mitochondrial classes and/or other subcellular components. PMID- 8507306 TI - Nuclear magnetic resonance characterization of secondary mechanisms following traumatic brain injury. AB - Much of the injury that occurs following a traumatic insult to the central nervous system is the result of physiological and biochemical processes initiated by the primary traumatic event. These processes occur over a period of hours to days following the insult, and although a number of factors have been identified as being associated with this secondary injury process, their role and interrelationship with one another is unclear. Nuclear magnetic resonance spectroscopy has been utilized to characterize many of these secondary factors and their relationship to eventual neurological outcome. In particular, the role of high energy phosphates, pH, lactic acid, excitatory amino acids, and magnesium has been investigated, along with pharmacotherapies directed toward altering the status of these factors following traumatic injury. This review critically examines the role that each of these factors may play in the secondary injury process, and proposes a scheme which theoretically accounts for the interrelationships among the various factors. PMID- 8507305 TI - Analysis of the sequence and embryonic expression of chicken neurofibromin mRNA. AB - Neurofibromatosis type 1 (NF1) is a common inherited disorder that primarily affects tissues derived from the neural crest. Recent identification and characterization of the human NF1 gene has revealed that it encodes a protein (now called neurofibromin) that is similar in sequence to the ras-GTPase activator protein (or ras-GAP), suggesting that neurofibromin may be a component of cellular signal transduction pathways regulating cellular proliferation and/or differentiation. To initiate investigations on the role of the NF1 gene product in embryonic development, we have isolated a partial cDNA for chicken neurofibromin. Sequence analysis reveals that the predicted amino acid sequence is highly conserved between chick and human. The chicken cDNA hybridizes to a 12.5-kb transcript on RNA blots, a mol wt similar to that reported for the human and murine mRNAs. Ribonuclease protection assays indicate that NF1 mRNA is expressed in a variety of tissues in the chick embryo; this is confirmed by in situ hybridization analysis. NF1 mRNA expression is detectable as early as embryonic stage 18 in the neural plate. This pattern of expression may suggest a role for neurofibromin during normal development, including that of the nervous system. PMID- 8507307 TI - Toluene-induced oxidative stress in several brain regions and other organs. AB - The in vivo dose-response relationship between toluene and reactive oxygen species (ROS) formation in rat brain, liver, kidney, and lung, and the time course of these effects has been characterized. The rate of oxygen radical formation was measured using the probe 2',7'-dichlorofluorescin diacetate. In vivo exposure to various doses of toluene (0.5, 1.0, and 1.5 g/kg ip) elicited a dose-dependent elevation of ROS generation within crude mitochondrial fractions obtained from rat lung and kidney, and within crude synaptosomal fractions from cerebellum. ROS formation in crude mitochondrial fractions from liver, and crude synaptosomal fractions from striatum and hippocampus, reached a maximum value at relatively low doses of toluene. Of the brain regions, the hippocampus had the highest induced levels of ROS. In vivo exposure to a single dose of toluene (1.5 g/kg ip), revealed that toluene-induced ROS reached a peak within 2 h, which correlated directly with measured toluene blood levels. This elevated oxidative activity was maintained throughout the next 24 h, even though blood values of toluene decreased to negligible amounts. These results demonstrate that exposure to toluene results in broad systemic elevation in the normal rate of oxygen radical generation, with such effects persisting in the tissues despite a rapid decline in toluene blood levels. Acute exposure to toluene may lead to extended ROS-related changes, and this may account for some of the clinical observations made in chronic toluene abusers. PMID- 8507308 TI - Proceedings of the AAMC'S Consensus Conference on the Use of Standardized Patients in the Teaching and Evaluation of Clinical Skills. Washington, D.C., December 3-4, 1992. PMID- 8507309 TI - An overview of the uses of standardized patients for teaching and evaluating clinical skills. AAMC. AB - The author defines the term standardized patient (SP), the umbrella term for both a simulated patient (a well person trained to simulate a patient's illness in a standardized way) and an actual patient (who is trained to present his or her own illness in a standardized way). He first discusses the many values of simulated patients over actual patients as teaching and assessment tools in the classroom and refutes a few myths about the use of SPs. Then he recounts the origin and development of SPs over a three-decade period, beginning with his work as a neurologist at the Los Angeles County Hospital, where he trained a model from the art department to simulate a neurological patient and assist in the assessment of clinical clerks. He then describes additional roles of SPs that have developed, including: (1) their use in the Clinical Practice Examination created at Southern Illinois University School of Medicine and (2) the major use that has come into being over the last 10-15 years; facilitating the comprehensive assessment of clinical competence using multiple stations in examinations such as the objective structured clinical examination. He concludes with information about recent and current work on SPs, who are becoming more and more accepted in the assessment process, and urges skeptics not to make judgments about the value of SPs until they have experienced the technique firsthand and reviewed the literature concerning the extensive and often high-quality research about this assessment tool. PMID- 8507310 TI - Technical issues: test application. AAMC. AB - Eighteen questions are posed that the authors believe address the major technical issues involved in the application of standardized patients (SPs). Following each question, selected empirical evidence and commentary are provided in response to the question and as background for further consideration of the issues. The authors conclude that the evidence from this large and systematic knowledge base about SP examinations is encouraging and should be cause for optimism. Moreover, it is noted that far less is known about the measurement properties of conventional procedures for clinical assessment in medical school courses and clerkships. The collective evidence from this extensive SP research base suggests that medical educators should move ahead to realize the benefits of the high fidelity standardized approach provided by standardized-patient examinations. PMID- 8507312 TI - Perspectives for curriculum renewal in medical education. PMID- 8507311 TI - Technical issues: logistics. AAMC. AB - The author states that she became interested in standardized patients (SPs) around 20 years ago as a means of developing a more uniform and effective way to provide instruction and evaluation of basic clinical skills. She reflects upon in detail: (1) the logistics of using SPs in teaching; (2) how SPs are used in assessment; (3) what aspects of performance SPs can be trained to record and evaluate; (4) issues concerning checklists; (5) evaluation of interviewing skills; (6) evaluation of written communication skills; (7) importance of defining what is being tested; (8) various kinds and uses of inter-station exercises and problems of scoring them; (9) case development and the various sources for case material; (10) ways to generate scores; (11) selecting and training SPs; (12) role of the faculty and primary importance of bedside training with real patients; and (13) pros and cons of national versus single-school efforts to use SPs. She concludes by cautioning that further research must be done before SPs can be used for high-stakes certifying and licensing examinations. PMID- 8507313 TI - Academic medicine's role in shaping U.S. science policy. PMID- 8507314 TI - Calculating the number of new generalist physicians. PMID- 8507315 TI - The Graduation Questionnaire and graduates' subspecialty plans. PMID- 8507316 TI - The need to promote CAI. PMID- 8507318 TI - The black academic psychiatrist. PMID- 8507317 TI - Admission interview scores and dean's letter ratings. PMID- 8507319 TI - Results of the National Resident Matching Program for 1993. PMID- 8507320 TI - Educational debt, specialty choices, and practice intentions of underrepresented minority medical school graduates. PMID- 8507321 TI - Educating medical students. Assessing change in medical education--the road to implementation. PMID- 8507322 TI - Of warps and woofs: the tapestry of medical education. AB - The author likens some major aspects of academic medical centers to tightly and carefully woven tapestries. The metaphor is intended to highlight the complexity of medical centers and to help those who are working to promote meaningful and sustainable innovations in medical education. Underlying the presentation is the premise that there already exist several "good ideas" to improve medical education, and that deeper understanding of the barriers to change can promote adoption of these ideas and others. Three tapestries are presented. Each has a vertical "warp" representing one dimension of an academic medical center, and each has a horizontal "woof" representing an interrelated dimension. (In one tapestry, for example, departmental resources constitute the warp and the faculty functions of teaching, research, and service constitute the woof.) In each tapestry, the warp is presently the dominant feature. In each, strengthening or empowering the woof is seen as a step that would facilitate change. Because educational change is a difficult and inevitably slow process, those who work for change are counseled to be patient and have realistic expectations. PMID- 8507323 TI - Medical education in the United States and Canada revisited. PMID- 8507324 TI - The use of removable artificial gingiva in laboratory procedures for periodontal and implant prostheses. AB - This paper describes a laboratory procedure for use in periodontal and implant prostheses wherein an artificial removable gingiva, which reproduces the patient's gingival architecture, is fabricated on the working cast. This procedure allows the technician to achieve better crown contour and cervical adaptation of the prosthesis and facilitates ceramic procedures. PMID- 8507325 TI - Influence of the dimensions of implant superstructure on peri-implant bone loss. AB - Two groups totaling 81 patients were selected. One group of edentulous patients had two IMZ implants, a bar, and an overdenture placed. The second group received a fixed restoration supported by one IMZ implant and one natural tooth. A superstructure constant was defined and used to combine the length and height of the Dolder bar or fixed prosthesis. Radiological bone loss was compared to the dimensions of the superstructure. The results showed a clear optimum for the dimensions of the superstructure on implants for the edentulous patient. Two implants connected with an overdenture should be placed 22 to 27 mm (between the centers of the implants) apart for best results. For fixed partial dentures no optimum dimensions could be found. PMID- 8507326 TI - Influence of finish-line geometry on the fit of crowns. AB - Previous studies on the fit of complete crowns have neglected to assess the internal adaptation of castings prior to cementation. Theoretical arguments and laboratory studies have failed to clarify which is the most desirable finish-line configuration in terms of marginal fit. This study evaluated axial and marginal fit of crowns made for three tooth preparations that had different labial finish line configurations: shoulder, shoulder-bevel, and chamfer. The crowns were not cemented, but were sectioned and examined on their respective dies. There were no significant differences (P < or = .05) among groups for marginal or axial gaps. Crown fit was not influenced by any of the three finish lines tested, and castings with well-fitting margins exhibited measurable axial wall space. PMID- 8507327 TI - Cryo-SEM evaluation of desiccation-sensitive dental specimens. AB - As a result of desiccation, conventionally prepared fresh dental specimens, examined with the scanning electron microscope (SEM), exhibit obvious artifactual effects that may include one or more of the following: distortion, fracture, separation of structures, and chemical interactions. Cryo-SEM techniques reduce or eliminate these artifacts and present reliable images while requiring less time to perform than do conventional methods. PMID- 8507328 TI - Comparison of fit of porcelain veneers fabricated using different techniques. AB - This investigation examined the influence of the fabrication technique on the marginal fit of porcelain veneers. Ceramic veneer restorations were made with both feldspathic porcelain and cast glass ceramic materials for the labial surface of a maxillary central incisor. The feldspathic porcelain veneers were made by using both the platinum foil and refractory die techniques, and the cast ceramic veneers were fabricated in thicknesses of 0.5 mm and 1.0 mm. The fit of each veneer was measured before and after sectioning. The marginal openings for the intact veneers increased in the following order: platinum foil, refractory die, cast ceramic (0.5 mm), and cast ceramic (1.0 mm). A similar trend was observed for the sectioned specimens where the technique of fabrication (P < .001) and the site of measurement (P < .05) were found to have a significant effect on the fit of the veneers. PMID- 8507329 TI - Effect of soft denture liner on stress distribution in supporting structures under a denture. AB - This study examined the effect of a soft denture liner on the distribution of stresses in the denture-supporting structures. Dentures without a linear and with three configurations of a soft liner were simulated by using a two-dimensional viscoelastic finite-element stress analysis. The stress intensity at functional force-bearing areas decreased when a soft denture liner was used. However, the stresses in the bone increased remarkably up to 3.0 seconds after loading. Because of the time-dependent effect of stresses applied to soft denture liners, denture patients who clench or brux may not benefit as greatly from soft denture liners. The study indicates that viscoelastic finite-element analysis is helpful for evaluating soft denture liners. Soft denture liners appear to be useful for improving the stress distribution in the supporting structures under dentures. PMID- 8507330 TI - A variation in minor connector design for partial dentures. AB - Whenever possible, the minor connector of a removable partial denture is located in the interdental embrasure. Recent evidence suggests that gingival attachment loss is more probable on the proximal aspect, thus minor connectors located in embrasures cover susceptible sites. A rationale and design are presented for locating the minor connector on the lingual aspect of the abutment tooth rather than in the interproximal area. PMID- 8507331 TI - Evaluation of tin plating systems for a high-noble alloy. AB - The tensile bond strength of Panavia EX to a high-noble alloy prepared by abrasive spraying and tin plating was measured. Two different intraoperatory tin plating systems were compared. Disk-shaped specimens were cast in type III gold, abrasive sprayed with aluminum oxide, and divided into three groups of 30 specimens each. Specimens in one group were tin plated by using a Kura Ace Mini unit, those in the second group were tin plated by using a Micro Tin unit, and those in the third group were not tin plated and served as the control group. Disks within each group were luted to each other with Panavia EX. The specimens were thermocycled and tested in tension. There was no significant difference between the two tin plated groups; however, the luting bond of both experimental groups was significantly stronger than was that of the control (P < .05). PMID- 8507333 TI - Dual interlocking tracheostoma vents. AB - This article describes a technique for fabricating interlocking custom tracheostoma vents for use in patients with bidirectional tracheostomas or tracheostoma fistulas secondary to tracheostenosis. The interlocking nature of the tracheostoma vents allows easy placement and removal from a tracheostoma or tracheostoma fistulas that would not be possible with a single tracheostoma vent. A 5 x 10-mm opening in the inferior portion of the prosthesis allows the patient with intact vocal cords to phonate by occluding the opening of the prosthesis and forcing air through the prosthesis into the subglottal area. The rigid acrylic resin of the prosthesis maintains the patency of the tracheostoma or tracheostoma fistula while a resilient material in the peristomal area reduces the pressure and potential irritation. The steps involved in the fabrication of the dual interlocking custom tracheostoma vents are easy and require no elaborate laboratory equipment. PMID- 8507332 TI - Strength of magnesia-core crown with different body porcelains. AB - The diametral strengths of magnesia-core crowns made with different body porcelains, Will-Ceram, Crystar, Ceramco II, and Vita VMK 68, were measured. The results were compared to the diametral strengths of aluminous-core crowns and Renaissance crowns. A one-way analysis of variance showed that there were no significant differences in the strengths of magnesia-core crowns or the aluminous core crowns, but the Renaissance crown strengths were significantly lower. PMID- 8507334 TI - Prosthodontics-a cerebral specialty. PMID- 8507335 TI - The effects of various disinfectant solutions on the surface hardness of an acrylic resin denture base material. AB - There is an increasing awareness of the importance of cross-infection control in dental clinics and laboratories. This study evaluates the effects of various disinfecting solutions on the surface hardness of an acrylic resin denture base material. Hardness was measured as resistance to indentation following the method specified by the British Standards Institute. The results demonstrated that immersion of denture base acrylic resin in disinfecting solution for up to 24 hours resulted in no significant effect on hardness values. PMID- 8507336 TI - Geriatric University Clinic has standardized pressure ulcer prevention methods. PMID- 8507337 TI - Likely health plan: more coverage ... less choice. PMID- 8507338 TI - Figure it out! PMID- 8507339 TI - Establishing a continence service using AHCPR guidelines. AB - The Agency for Health Care Policy and Research (AHCPR) has recently released practice guidelines for the management of adult urinary incontinence. The guidelines are designed to enhance the quality, effectiveness and appropriateness of health care in the area of incontinence. The purpose of this article is to describe assessment and management strategies as used in a continence clinic that incorporate AHCPR guidelines. This continence clinic exists within an established gynecology practice, however, continence services can be provided in nursing homes and/or home care agencies. PMID- 8507340 TI - (Non) compliance. PMID- 8507341 TI - Effectiveness of an OTC topical antifungal powder. AB - Independent clinical testing of products provide unbiased data for practicing clinicians to make an informed decision when confronted with the evaluation of new products. This study examines the effectiveness of an OTC antifungal powder on a small patient population (N = 33) with cutaneous monilial infections. Results and recommendations are discussed. PMID- 8507342 TI - Case study: stoma relocation. AB - Stoma site relocation presented management problems in a 78 year old female. The old stoma site, located close to the new site, deteriorated due to the patient's debilitated condition. A wound care program was needed that incorporated simplicity and debridement for yellow slough. PMID- 8507343 TI - Wound care practices in the United States. AB - Wound management is a crucial aspect of patient care and the nurse often is faced with the question of which approaches to use to provide an environment that supports healing and prevents complications. Important questions include how different types of wounds should be dressed, what method of debridement to use, whether dressings should be changed using sterile versus unsterile technique, and which adjunctive therapies to select under given circumstances. These topics are of interest to clinicians as they represent actual clinical practice and some of the major debates among health care providers who are trying to determine which practices to use to optimize wound healing. While studies are available that compare specific products, no data are available at this time regarding the current wound care practices in the United States. If data documenting the existing wound care practices were available, they would increase understanding of how other professionals manage wound care and provide the basis for planning patient care as well as educational programs and research on wound care. PMID- 8507344 TI - Wound care products. PMID- 8507345 TI - New device protects skin from AIDS virus and other blood pathogens. PMID- 8507346 TI - Neuroendocrine and cardiovascular effects of MDE in healthy volunteers. AB - The drug 3,4-methylenedioxyethamphetamine ([MDE] also known as "Eve") is a less toxic analog of 3,4-methylenedioxymethamphetamine (also known as "Ecstasy") with similar psychotropic effects in humans. In a double-blind placebo-controlled, cross-over study we administered 140 mg of MDE or placebo orally to eight healthy male volunteers at 1:30 P.M. Serum cortisol, prolactin (PRL), and growth hormone (GH) levels, as well as blood pressure, and heart rate were measured every 20 minutes until 5:00 P.M. Administration of MDE was followed by statistically significant long-lasting increases of serum cortisol, PRL, systolic blood pressure, and heart rate, and by a trend toward blunting of GH secretion. The neuroendocrine and cardiovascular effects of MDE are comparable to those of other phenethylamines with the exception of the effect on GH secretion. PMID- 8507347 TI - Selective effects of low-dose D2 dopamine receptor antagonism in a reaction-time task in rats. AB - Operant responses involving a cued discrimination are sensitively disrupted by neuroleptic drugs that block dopamine (DA) receptors in the brain; however, it is not clear which DA receptor subtypes may be involved in these effects. The role of D1 or D2 DA receptor antagonists on the execution of a conditioned reaction time (RT) motor task was investigated in the present study. Rats were trained to release a lever after the presentation of a visual cue within a RT limit to be reinforced by a food pellet. The D1 receptor antagonist SCH-23390, at doses that significantly decrease the behavioral effects of cocaine, did not impair performance at any dose (5, 10, or 20 micrograms/kg) injected subcutaneously. In contrast, a selective D2 receptor antagonist raclopride (50, 100, or 200 micrograms/kg) induced a dose-dependent increase in the number of incorrect responses (release of the lever over the RT limit) associated with an increase in the RT. The results suggest that the dopaminergic nigrostriatal system, which has previously been shown to be specifically involved in this RT task (Amalric and Koob 1987), appears to be a sensitive site for sensorimotor integration, and that the execution of the conditioned RT motor task may depend preferentially on the activation of the dopaminergic D2 receptors in this system. PMID- 8507348 TI - Lisuride reduces psychomotor retardation during withdrawal from chronic intravenous amphetamine self-administration in rats. AB - Withdrawal from chronic use of psychostimulant drugs in humans induces a clinical syndrome characterized by fatigue, psychomotor depression, anhedonia, and disturbances of sleep. Spontaneous locomotor activity and catalepsy were assessed in rats during withdrawal from a schedule of intravenous self-administration of high doses of amphetamine. At 2 and 4 days after cessation of amphetamine self administration, rats showed a state of psychomotor retardation as measured by reduction of locomotor activity and increased catalepsy. In search of a possible pharmacologic means of intervention for such behavioral changes, the effect of repeated treatment with the nonaddictive ergot derivative lisuride during the withdrawal phase was evaluated. At a dose devoid of any effects on locomotor activity, lisuride completely prevented the reduction in locomotor activity and the increase in catalepsy produced by amphetamine withdrawal. These results suggest the need for further studies on lisuride as a possible novel treatment during withdrawal from psychostimulant drugs in humans. PMID- 8507349 TI - Adrenal steroids mediate the increase of hippocampal nerve growth factor biosynthesis following bicuculline convulsions. AB - Northern blot analysis of nerve growth factor (NGF) messenger ribonucleic acid (mRNA), together with a two-site enzyme immunoassay for NGF protein, showed that a convulsive dose of bicuculline (0.4 mg/kg, IV) induced a rapid (within 1 hour) three-fold increase in hippocampal NGF mRNA. This increase was followed by a significant increase in NGF protein 5 hours later. No changes were detected in the cerebral cortex. The increase of rat hippocampal NGF mRNA and protein content was associated with an increase in plasma corticosterone content. Both responses were completely prevented by a pretreatment with diazepam (5 mg/kg, IP), which suggested that adrenal steroids might be a stimulus underlying the rapid increase in NGF biosynthesis following bicuculline convulsions. Therefore, we tested to determine whether a convulsive dose of bicuculline could increase NGF mRNA in adrenalectomized and sham-operated rats. Bicuculline increases hippocampal NGF mRNA in sham-operated rats, but not in adrenalectomized rats despite the presence of convulsions in both experimental groups. Moreover, in adrenalectomized rats, dexamethasone (0.5 mg/kg, SC) could partly restore the increase in hippocampal NGF mRNA content induced by bicuculline convulsions; thus, adrenal steroids might have an essential role in the induction of hippocampal NGF biosynthesis elicited by bicuculline convulsions. PMID- 8507350 TI - Effects of triazolam and nifedipine injections into the medial preoptic area on sleep. AB - We have reported previously that microinjections of the benzodiazepine (BZ) hypnotic triazolam into the medial preoptic area (MPA) of the hypothalamus increase sleep in the rat. As a follow up to previous work, which has indicated that the dihydropyridine calcium channel blocker, nifedipine, prevents sleep induction by an intraperitoneally administered BZ, we have now coinjected nifedipine and triazolam into the MPA. It was found that nifedipine alone had no significant effects on sleep and prevented sleep induction by triazolam. There were no drug-specific effects on core temperature in any treatment condition. These data suggest that dihydropyridine-sensitive sites may be involved in the mechanism of sleep induction by BZs. PMID- 8507351 TI - Reanalysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program General Effectiveness Report. AB - The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program General Effectiveness Report statistical analyses are criticized. Their analyses, which fostered the belief that criticized. Their analyses, which fostered the belief that the active treatments were indistinguishable, were compromised by an inappropriately stringent level of significance with regard to both heterogeneity of slope and pairwise group differences. Once slope heterogeneity is detected, the Johnson-Neyman technique is more appropriate than arbitrary sample subdivision. All of these tactics lowered power substantially. Our reanalysis indicates a reasonable ordering for the treatments with medication superior to the psychotherapies and the psychotherapies somewhat superior to placebo. These effects are particularly marked among the more symptomatic and impaired patients. The lack of dosage by severity analyses renders the severity findings ambiguous. Scientific and public health implications are discussed. PMID- 8507352 TI - Chronic continuous or intermittent infusion of cocaine differentially alter the concentration of neurotensin-like immunoreactivity in specific rat brain regions. AB - Neurotensin (NT) is an endogenous brain tridecapeptide that exhibits selective anatomic and neurochemical interactions with rat brain dopaminergic systems. Because modulation of dopaminergic neurotransmission may underlie many of the behavioral properties of cocaine, the effects of both acute and chronic administration of cocaine on the concentration of NT-like immunoreactivity (NT LI) in specific brain regions was determined. Adult male rats were treated with cocaine for 14 days at a dose of 40 mg/kg/day (0.118 mmoles/kg/day) administered as either 1 subcutaneous injection per day, or infused continuously using subcutaneously implanted minipumps. Neurotensin-like immunoreactivity in specific brain regions was then measured 24 hours or 8 days following drug administration. After 24 hours of withdrawal from daily subcutaneous injection, the concentration of NT-LI was significantly increased in the substantia nigra (SN) and frontal cortex. After 24 hours of withdrawal from continuous infusion with cocaine, NT-LI was increased only in the SN. After 8 days of withdrawal, NT-LI was increased in the SN of rats treated with daily subcutaneous infections of cocaine, but not in the group treated with continuous infusion. Twenty-four hours following a single acute injection of 40 mg/kg of cocaine, NT-LI was increased in the SN and nucleus accumbens. These results provide evidence consistent with a neuroanatomically selective involvement of NT systems in the behavioral and/or addictive properties of cocaine. PMID- 8507353 TI - 125I embedded in an orbital prosthesis for retreatment of recurrent retinoblastoma. AB - The application of radiation therapy in the retreatment of unilateral recurrent retinoblastoma presents a very difficult dilemma in which consideration must be given to preservation of vision in the remaining eye while tumoricidal doses of irradiation are delivered. A technique is described in which a methylmetraculate eye sphere carrying a single Iodine-125 seed was used to deliver local irradiation to the orbital tissues in a patient with multiple episodes of recurrent retinoblastoma. The tissue dose at 2 mm depth was 2630 cGy while the dose to the retina of the remaining eye and to the optic chiasm was negligible. PMID- 8507355 TI - A PC BASIC program to double-check treatment planning calculation. AB - To ensure quality assurance at The New York Hospital, the treatment plans are checked manually and then double-checked. The goal is to ensure that the dose at the normalization point adds up to the correct value. This double checking procedure can become cumbersome. A BASIC program was written to help speed up the procedure. The program was written on an IBM personal computer. The program also has an option to calculate doses at various points along the central axis with respect to the isocenter dose. The program requires the user to answer a few simple questions to help perform the appropriate calculations. The programs are used only as a double check on the hand calculations. PMID- 8507354 TI - Movements of the prostate due to rectal and bladder distension: implications for radiotherapy. AB - Precision radiotherapy depends upon the accurate definition of a target volume. Conformal therapy of prostate cancer requires an understanding of the prostate volume and its potential movements. This study was performed to quantify movement of the prostate due to rectal or bladder distention. Eighteen men with localized prostate cancer (clinical stages A, B, and C) were included in this study. Following simulation, treatment planning computed tomography (CT) scans were performed. The scans were first obtained with a small amount of contrast in the rectum and the bladder. Identical CT cuts were then obtained after filling the rectum with contrast. In 11 patients, the bladder was then filled with contrast and the same CT cuts were obtained again. Movement of the prostate and seminal vesicles secondary to distension of the rectum and bladder was measured. Distension of the rectum shifted the posterior margin of the prostate anteriorly from 0 to 0.9 cm. (median = 0.1 cm). The posterior border of the prostate was displaced anteriorly by more than 0.5 cm in 3 of the 18 (17%) patients with rectal distension. Distension of the bladder shifted the posterior border of the prostate posteriorly from 0 to 0.8 cm. (median = 0.2 cm). The posterior border of the prostate was shifted more than 0.5 cm. in 1 of 11 (9%) patients with bladder distension. Movements of other margins of the prostate and seminal vesicles were measured. The available literature is reviewed and suggestions are given regarding the movement of the prostate and treatment planning. PMID- 8507356 TI - Comparison of CT-based treatment planning and retrograde urethrography in determining the prostatic apex at simulation. AB - In 20 consecutive patients who underwent treatment planning, localization of the prostatic apex with CT-based techniques at simulation was compared to location of the apex as defined by retrograde urethrography. In addition, the location of the urethrogram-defined prostatic apex was compared with the bottom of the ischial tuberosities, which is often recommended as the inferior margin of the field. In 15% of the patients there was agreement between the CT-defined apex and the urethrogram-defined apex; in 85% there was discordance. In a majority of patients with discordance, the urethrogram apex was located caudad to the CT-defined apex (71%) with a median difference of .65 cm. In 29% of the patients the urethrogram apex was located superior to the CT-defined apex. Overall, 75% of the patients had discordance between the urethrogram apex and the CT apex of 0.5 cm or greater; 30% had an absolute difference of 1.0 cm or greater. Comparing the location of the prostatic apex with the bottom of the ischial tuberosities revealed that in 15% of the patients the apex was 1.0 cm or less from the bottom of the tuberosities and in 45% it was less than 1.5 cm. This would place the apex of the prostate in the penumbra region of the field and risk undertreatment of the prostate if the bottom of the ischial tuberosities was the inferior margin of the field. Measuring the location of the prostatic apex from the top of the symphysis pubis revealed that a distance of 4.9 cm encompassed the apex in all 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507357 TI - The use of integral activity to assess scheduled radioactive source changes for brachytherapy. AB - The development of afterloading brachytherapy devices using radioactive sources with relatively short half-lives has meant that several source changes are required per year. We present here a simple method to evaluate the ability of the supplier to deliver the scheduled amount of activity. Using the integrated activity of the source during the period of its clinical use, a comparison between the scheduled and delivered activity can be quantified. PMID- 8507358 TI - Seed strength determination for eye plaque therapy. AB - Standardized radioactive plaques have been used in the irradiation of intraocular tumors. These plaques have defined slots to accommodate 125I seeds and hence produce predictable isodose distributions. The seed strength has to be adjusted to deliver 100 Gy to the prescription point, which varies with the tumor size. The purpose of this work is to develop lookup tables that relate the seed strength to different prescription distances. Dose rates were determined for a set of standardized eye plaques. Using these dose rates and the source strength decaying expression, the seed strengths were determined as a function of distance along a line through the plaque. Two seed-strength tables were created based on four-day and five-day treatment times delivering a 100 Gy to the prescription distance. PMID- 8507359 TI - An afterloading 192Ir surface mold. AB - Patients with basal cell skin cancer can be treated with afterloading 192Ir surface molds constructed from dental wax. High activity 192Ir seeds in ribbons are distributed in the mold to uniformly irradiate the target volume. The treatment is preplanned with a treatment planning system to achieve a uniform dose distribution in the planned target volume. The implant parameters optimized include the seed strength and number of seeds, inter- and intracatheter spacing between 192Ir seeds, and the distance between the implant and treatment planes. The radioactive 192Ir strands are afterloaded in the catheters embedded in the wax mold and the position secured with buttons. The treatment area drawn on the patient surface is visually overlapped with the uniformly irradiated area sketched on the mold surface. The mold is taped to the head to secure this position. The dose rate on the surface of the mold in contact with the patient skin is measured with calibrated LiF TLD chips and is within +/- 5% of the computer preplanned dose rate value. This technique is a viable alternative to external beam treatments when daily treatments are not feasible and a dose distribution conforming to the treatment area is desirable. PMID- 8507360 TI - Transmission block technique for the treatment of the pelvis and perineum including the inguinal lymph nodes: dosimetric considerations. AB - Radical radiotherapy of pelvic malignancies (e.g., vulva, anus) includes therapeutic dosage to the inguinal nodes. To minimize the dosage to the femoral head, the transmission block technique has been developed to fully irradiate the central pelvis midplane and inguinal nodes. Originally, this technique compensated for dose inhomogeneity in the transverse plane only. In some patients, however, we have observed a significant dose variation along the sagittal plane. The authors have developed a lead compensation technique to homogenize the sagittal dose variations due to the longitudinal sloping in the patient, along with further refinements in this technique. Dosimetric and technical details are also discussed. PMID- 8507361 TI - Intravenous Pluronic F-127 in early burn wound treatment in rats. AB - A dramatic improvement in full skin thickness burn wounds in rats treated intravenously with the non-ionic surfactant Pluronic F-127 (F-127) has been demonstrated. In this study the F-127 was given 30 min postburn to simulate conditions encountered in a clinical setting. Anaesthetized male rats (300-320 g) received full skin thickness burns by immersion of the anterior chest wall (8 per cent body surface area in a 70 degrees C water-bath for 12 s). Burn wound area was measured immediately and after 48 h. Thirty minutes after the burn, half the animals received equal volumes (8 ml/kg body wt) of either saline or F-127 (12 mM/l concentration) via the tail vein. The animals autopsied at 48 h showed a significant (P < 0.05) reduction in the degree of wound contraction and the wound appeared grossly less damaged in the F-127-treated animals. Histologically, skin biopsies showed less of the microscopic damage usually associated with full skin thickness burns in the F-127-treated animals than in the saline controls. We also used thermography to measure skin temperature of the burn area at 90 min and 48 h postinjury demonstrating alterations in the F-127-treated animals (P < 0.05). In animals followed for 30 days postinjury, there was a significant (P < 0.01) improvement in the wound closure rates in the F-127-treated animals. These observations show a positive therapeutic effect of F-127 on the inflammatory process in the area of a burn that may improve wound healing. PMID- 8507362 TI - Burns in the disabled. AB - A retrospective analysis of 812 patients admitted to the Ross Tilley Burn Centre between 1984 and 1992 resulted in 37 cases of burn injuries which were directly related to premorbid disabilities. The majority of these burns (83.8 per cent) occurred in the patient's home, most commonly as scald injuries in the bath tub, the shower, or following hot water spills. Nineteen patients were male, 17 were female. The median age was 58 years. Six patients had spinal cord disorders: four had traumatic cord damage, two had spina bifida. Six patients had seizure disorders. Five of these patients had been taking anti-seizure medications, but all had subtherapeutic blood levels on admission to hospital. Two patients had diabetes mellitus with peripheral neuropathies. Thirteen patients had four miscellaneous neurological disorders, including: tardive dyskinesia (two), CVA (four), Parkinson's disease (two), Alzheimer's disease (two), cerebral palsy (one), multiple sclerosis (one) and blindness (one). Three patients had a diagnosis of syncope. Two patients had emphysema, and four were morbidly obese. The average length of stay (LOS) for the disabled patients was 27.6 days for a median burn size of 10 per cent body surface area (BSA), compared to an average LOS for the general population of 25.7 days for a larger median burn size of 21 per cent BSA. The mortality rate was also much higher in the disabled population (22.2 per cent vs. 6.0 per cent). Most of these burn injuries were preventable. A series of burn prevention guidelines is presented, in an attempt to reduce the incidence of these burn injuries in disabled patients. PMID- 8507363 TI - Prognostic value of the CD4/CD8 lymphocyte ratio in moderately burned patients. AB - We investigated CD3+, CD4+ and CD8+ T-cell subpopulations, as well as the CD4/CD8 ratio in 84 moderately burned patients with injuries affecting 11-36 per cent of their total body surface area (TBSA). These lymphocyte subpopulations were quantified by indirect immunofluorescence measurement 7 and 60 days postburn. The results obtained 7 days postburn were highly significant in those patients who developed septicaemia, all of whom had considerably decreased CD4+ and increased CD8+ T-cell numbers, as well as inverted CD4/CD8 ratios. Consequently, the CD4/CD8 ratio may provide valuable information for prognosis of patient evolution and the establishment of early treatment in order to avoid likely future complications. PMID- 8507364 TI - Effects of a platelet activating factor antagonist on oedema formation following burns. AB - Deep dermal burns covering 30 per cent of the total body surface area were prepared by immersing the backs of rabbits in hot water at 80 degrees C for 20 s, to determine whether platelet activating factor (PAF) was involved in the onset of oedema following burns and to evaluate the effect of TCV-309, a potent PAF antagonist. The PAF antagonist, which was infused soon after the burn, blocked oedema formation in the wound and significantly (P < 0.001) inhibited PAF increase (P < 0.05) in the damaged tissue in a dose-dependent manner. This was confirmed by immunohistochemistry. In contrast, the superoxide dismutase content in the group treated with a high dose of TCV-309 was significantly (P < 0.01) higher than that of the control group. These findings suggest that administration of large doses of a PAF antagonist immediately after injury prevents oedema of burn wounds and the subsequent onset of burn shock by suppressing PAF and superoxide radical formation. PMID- 8507365 TI - Allogeneic microskin grafting of rabbits' skin wounds. AB - Allogeneic microskin grafts (expansion ratio of 10:1), overlain with Biobrane, were applied to 30 rabbits. There were two groups. In group I, the allogeneic donor microskin grafts were transplanted without specific management. In group II, the donor skin was treated with ultraviolet (312 nm) irradiation to depress Langerhans cells immediately before the transplantation. Histological examination of these grafted wounds in the early stage showed that these micrografts proliferated actively with increased mitotic figures and became regularly stratified under the conditions provided by the Biobrane. By day 9, these wounds in group I were almost resurfaced with neoepithelium. In group II, the rate of regeneration of the neoepithelium was slower than those of group I. Subsequently there was rejection with moderate mononuclear infiltration, hydropic degeneration and satellite necrosis of basal and suprabasal keratinocytes, and local destruction of epithelium. Grossly these reactions caused 'melting' of the neoepithelium and resulted in raw areas. These rejections were more severe about 2 weeks after transplantation and then subsided gradually. Mild cellular infiltration continued to prevent the formation of rete ridges and the dermoepidermal junction was smooth at all times. Langerhans cells could not be found in these grafted wounds using OKT-6 and S100 stain. In spite of the destruction caused by these rejections in both groups, 25 wounds were completely resurfaced with well-differentiated neoepithelium by day 21. This study revealed that the transplanted allogeneic microskin grafts could proliferate to form neoepithelium and resurface the skin wounds of rabbits. PMID- 8507366 TI - An alternative treatment of massive burns: skin allografts and cyclosporin immunosuppression without severe additional depression of cell-mediated immunity in an animal model. AB - This study investigated the effects of early excision of eschar and grafting with cyclosporin immunosuppression on immunological changes following burn injury. The immunological status of the rat was studied using two in vivo measures following a (30 per cent TBSA) full skin thickness burn injury. Cyclosporin was found to be a powerful immunosuppressive agent in skin transplantation, and its risks, efficacy and possible side-effects after thermal injury have been investigated. This study demonstrated that a large burn was profoundly immunosuppressive, and early excision and grafting was able to restore cell-mediated immunity significantly as reflected by two in vivo assays. The short course of the immunosuppressive treatment to delay skin allograft rejection did not cause a severe additional effect on cell-mediated immunity after thermal injury. Allograft survival appeared to be related to immunosuppression caused mainly by cyclosporin treatment and also by the immunosuppressive effect of the burn. PMID- 8507367 TI - Incidence of ember burns in Andalusia (Spain). AB - A 6-year analysis of 2000 cases of burns was carried out. Half of the patients were from rural and the other half from urban locations. One hundred and sixty two patients out of the 2000 suffered from ember burns. The number of rural patients affected was greater than urban patients (117 vs. 45). Ember burns are frequent in Andalusia and have severe aesthetic and functional sequelae. Burns of this type are more common in children than in adults, so they carry an added social and medical relevance. PMID- 8507368 TI - Epidemiology of childhood thermal injuries in Enugu, Nigeria. AB - The results of a retrospective study of thermal injuries among 644 Nigerian children in Enugu, over a 6-year period, were analysed. Children in the first and second years of life were mostly at risk and there was a distinct seasonal incidence. Most burns occurred in January, April, July, August and December. Socioeconomic factors played a significant role in the aetiogenesis of these injuries. A mortality rate of 9.87 per cent was achieved in burns over 10 per cent of total body surface area (TBSA), despite considerable physical and financial constraints in the unit. PMID- 8507369 TI - A study of bone and joint changes secondary to burns. AB - A clinical and radiological study of 80 postburn patients to determine the extent of bone and joint changes is presented. The group comprised 38 males and 42 females, with ages ranging from 2 to 60 years. The time since burning ranged from 6 to 12 months in 40, from 1 to 5 years in 24 and over 5 years in 16 patients. Clinically bone and adjoining tissue involvement were seen in 32 patients (40 per cent), while radiological changes were seen in 49 (61.25 per cent). Radiological changes noted included osteoporosis 56.25 per cent, stunted growth (phalanges and limbs) 27.5 per cent, osteomyelitis 2.5 per cent, partial resorption of terminal phalanges and ankylosis 1.25 per cent each. Periarticular, pericapsular and tendon calcification were each seen in 1.25 per cent of the patients. Bone and joint changes were encountered only in major burns, and these could be minimized by proper early surgical care and long-term rehabilitation. PMID- 8507370 TI - Burn injuries in boating accidents. AB - We report a series of burn injuries sustained on boats and admitted to Stoke Mandeville Hospital over a 4-year period. Nine patients are presented, aged between 27 and 65 years. Total body surface area burned ranged from 1.5 to 83 per cent. The causes of the injuries, and the factors leading to the accidents which caused them, are discussed. Interviews with a number of private boat owners and hirers revealed an inadequate level of fire and safety precautions taken. There is at present no legal requirement for private boats to carry five fighting equipment. We believe there is a need for definition of the minimum legal level of such equipment to be carried on board. Increased awareness of correct fuel storage and handling requirements is felt to be important, especially with the increasing popularity of boating as a leisure and sporting activity. PMID- 8507371 TI - Specificity and treatment of thermal and inhalation injury following an explosion in a cement manufacturing kiln. AB - Six patients sustained a unique type of burn injury while working during the manufacture of cement in China. These patients suffered a combination of chemical and thermal injuries with extensive deep burns and inhalation injury, when they were involved in an accidental explosive leakage of cement from a manufacturing kiln. This report discusses the aetiology of the burn injury and the principles of treatment. All of these burns were preventable. PMID- 8507372 TI - The cost of an extensive burn survival. AB - A 17-year-old male sustained 95 per cent body surface area burns (87 per cent full thickness skin loss). He was hospitalized in the Department of Plastic Surgery that also treats burns. After 232 days he was discharged home when he was functionally independent. He had 16 surgical procedures for excision of burn eschar and skin grafting; received a total of 128 units of blood; 899 units of fresh frozen plasma and had enteral hyperalimentation for 175 days. About 1000 physician-hours, 3000 nurse-hours, 1000 physiotherapy and occupational therapy hours and about 250 dietician-hours were needed for his treatment. More than 1850 laboratory tests and 120 X-rays were performed, and more than 600 kg of ointment and creams were used, as well as half a ton of topical antimicrobial solutions. Ten different antibiotics were used for a total of 85 treatment days. Some 8500 m of dressing were applied with more than 6000 pieces of petroleum jelly gauze dressing. Hospitalization costs were found to be US$141,750, only 37.5 per cent of which were salaries. An analysis of these costs is given. PMID- 8507373 TI - Free flap necrosis: a self-inflicted burn. AB - A report of a sequence of self-inflicted thermal injuries which affected the elbow joint and later the thermal necrosis of a reparative flap. PMID- 8507374 TI - Postburn peroneal nerve palsy--a report of two consecutive cases. AB - We report two patients suffering from mixed deep partial and full skin thickness flame burns covering 45 and 95 per cent of the total body surface area respectively. These patients, following sepsis and multisystem failure, developed unilateral peroneal nerve palsy. The possible aetiology of isolated injury to the peroneal nerve in burned and critically ill trauma patients is discussed. PMID- 8507375 TI - Koebner's phenomenon in burns: another complication following thermal injury. AB - The Koebner phenomenon is an uncommon postburn complication. The following report describes the emergence of viral warts on the hand of a child, 6 months after sustaining a superficial scald. The aetiology and immunological implications are discussed. PMID- 8507376 TI - Burns depth index and classification of burns casualties. PMID- 8507377 TI - [Options in nursing]. PMID- 8507378 TI - [You can't have it both ways: report of the Commission Options in Health Care]. PMID- 8507379 TI - [You can't have it both ways. 'Official channels are lacking for dilemmas or options']. PMID- 8507380 TI - [You can't have it both ways. 'Our options do not exclusively concern money'. Interview with Prof. A.J. Dunning. Interview by Toine de Graaf and Tonny van de Pasch]. PMID- 8507381 TI - [Functional profile of psychiatric nursing]. PMID- 8507382 TI - [Environment and health care (12). Environment-preserving activities in the nursing department]. PMID- 8507383 TI - [WICSS, or the Weezenlanden Intensive Care Scoring System (1). A reliable workload measuring tool for the ICU]. PMID- 8507384 TI - [WICSS, or: the Weezenlanden Intensive Care Scoring System (2). To their satisfaction nurses are used with greater efficiency]. PMID- 8507385 TI - The effect of acute alcohol ingestion on Fc-receptor-mediated clearance of IgG tagged erythrocytes by the reticuloendothelial system in humans. AB - To help elucidate the pathogenesis of bacterial infections in alcoholics we documented reticuloendothelial system (RES) function in 14 healthy adults (9 males, 5 females, age: 22 +/- 2.6 years) prior to and following acute alcohol intoxication. Autologous erythrocytes were labelled with Cr51 isotope, tagged with anti-Rh IgG antibody, and infused into the systemic circulation. Blood samples were drawn at specific time intervals over a 2-h period and the radioactivity in each sample was used to develop computer-generated clearance curves from which half-lives (T1/2) were derived. Each study was carried out in the same individual on two separate occasions at least two weeks apart, once when sober and again one hour after ingestion of an intoxicating amount of alcohol (1 gm/kg over 1 h). Eleven of 14 participants showed no appreciable change in RES clearance capacity following alcohol ingestion. In the remaining three individuals alcohol prolonged the T1/2 by 38%, 38%, and 74% from when sober. These individuals were similar to other participants in terms of age, blood alcohol levels, pre- and postalcohol liver biochemistry, and hematologic and immunologic findings. Two of the three were HLA Dr5 positive, as compared to none of the 11 with unimpaired clearances. The results of this study suggest that perhaps a small subset of the population exists in whom acute alcohol intoxication impairs Fc-receptor-mediated RES clearance of IgG-tagged erythrocytes from the systemic circulation. This depression of RES function could contribute to the increased frequency and severity of bacterial infections reported in some alcoholics. PMID- 8507386 TI - Specific decreases in ethanol- but not water-reinforced responding produced by the 5-HT3 antagonist ICS 205-930. AB - The serotonin 5-HT3 antagonist ICS 205-930 has been shown to block the discriminative stimulus properties of ethanol and decrease voluntary intake, suggesting a possible role for 5-HT3 systems in the reinforcing effects of ethanol. ICS 205-930 (0.56, 1.0, 3.0, 10.0, and 17.0 mg/kg i.p.) was examined on ethanol and water self-administration in an operant paradigm. Following a sucrose fading procedure, two groups of nondeprived rats responded on either a concurrent fixed ratio 4 schedule for ethanol (10% v/v) and water (CONC FR4 FR4), or a single FR4 schedule for ethanol (10% v/v). ICS 205-930 dose-dependently decreased ethanol-reinforced responding in the concurrent condition without decreasing water-reinforced responding, suggesting a specific effect on ethanol. Ethanol reinforced responding was also dose-dependently decreased in the single FR4 condition, but the dose effect curve was shifted to the left. These data support the conclusions that 5-HT3 systems may play a specific role in ethanol self administration that is independent of general appetitive and motor processes, and that 5-HT3 antagonists may have therapeutic efficacy in the treatment of alcohol abuse when multiple reinforcers are available. PMID- 8507387 TI - The NMDA receptor antagonist MK-801 produces ethanol-like discrimination in the rat. AB - Two groups of rats, one derived from N/Nih stock and the second from the (putatively) serotonin-compromised Fawn-Hooded line, were trained to discriminate ethanol from its vehicle in a drug discrimination paradigm. Once each of the two groups attained discrimination criterion, dose-response relationships with lower doses of ethanol indicated that the Fawn-Hooded rats were less sensitive (ED50 value = 579.5 mg/kg) than the N/Nih rats (ED50 = 371.4 mg/kg). Testing of various doses of the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 produced complete generalization in each group of animals, with a similar difference in ED50 values between N/Nih and Fawn-Hooded lines. These results extend previous ethanol-to-MK-801 generalization reported in pigeon, and are discussed in light of a possible NMDA-mediated contribution to the ethanol-induced discriminative stimulus cues. PMID- 8507388 TI - Metabolism of acetaldehyde by rat isolated aortic rings: does endothelial tissue contribute to its extrahepatic metabolism? AB - Acetaldehyde (AcH) metabolism in isolated aortic rings was studied by assessing in vitro-added AcH disappearing rate by head space gas chromatography. It was found that AcH was metabolized by aortic rings or by homogenates prepared in 0.1 M phosphate buffer containing Triton X-100, by an NAD-dependent enzyme with characteristics similar to those of aldehyde dehydrogenase (AIDH) present in mitochondria from rat liver and brain. This enzyme appears to be present in the vascular endothelium, since the action of aortic rings showed a remarkable decrease by its removal. Extrahepatic metabolism of AcH was assessed by the differences between AcH levels found in samples of blood obtained from the suprahepatic vein, carotid artery, femoral vein, and tail cut of rats. The in vitro activity of aortic rings, as well as the extrahepatic AcH metabolism, were significantly decreased by pretreatment of rats with disulfiram. The wide distribution of vascular endothelium throughout the body suggests that this tissue could contribute to AcH extrahepatic metabolism. PMID- 8507389 TI - Effects of D1 and D2 dopamine receptor agents on ethanol consumption in the high alcohol-drinking (HAD) line of rats. AB - Dopamine receptor agonists and antagonists were tested for effects on alcohol drinking in female HAD rats (n = 10) given limited access (4 h/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Subcutaneous drug injections were given 30-60 min before the ethanol access periods. The D2 agonist quinpirole (0.04-2.0 mg/kg) caused a dose-dependent decrease in alcohol drinking throughout the 4-h period. Spiperone, a D2 antagonist, had no effect during the initial part of the session, but by the fourth hour, the 10 micrograms/kg dose tended to increase alcohol intake and the 30 micrograms/kg dose reduced intake. The D1 antagonist SCH-23390 (3-30 micrograms/kg) dose dependently decreased ethanol drinking during the first hour of access. The D1 agonist SKF-38393 (2-6 mg/kg) also decreased alcohol intake, but it was less effective than SCH-23390. The findings implicate both D1 and D2 receptors in the reinforcing effects of alcohol drinking by the HAD line of rats. PMID- 8507390 TI - Changes of auditory-evoked potentials in response to behaviorally meaningful tones induced by acute ethanol intake in altricial nestlings at the stage of formation of natural behavior. AB - Acute ethanol's influence on field L auditory-evoked potentials (AEP) was studied in 4-7-days-old altricial nestlings of the pied flycatcher. Nestlings were presented with behaviorally meaningful tone pips (2.0 and 5.0 kHz) and control tone pips (3.0 kHz). Ethanol ingestion was found to reduce the N1 amplitude and maturity index (MI) of the AEP in response to "behavioral" but not to control frequencies. This effect was first observed on day 5, when the nestlings' behavior became more complex (their eyes opened and defence behavior appeared), and when previously formed feeding behavior was undergoing modifications. The MI increase during the early postembryonic ontogeny was probably due to the selective involvement of neurons with newly formed behavioral specializations into the subserving of new behavioral patterns, while the decrease of the MI under alcohol was due to the depression of activity in these neurons. PMID- 8507391 TI - Involvement of the serotonergic system in ethanol intake in the rat. AB - A two-bottle, free-choice paradigm was used to investigate the influence of the serotonergic (5-HT) system on ethanol intake in genetically heterogeneous Wistar rats. Systemic administration of the 5-HT1A agonist ipsapirone (1.25-5.0 mg/kg) caused a dose-dependent decrease in ethanol preference and intake, while the 5 HT2 antagonist ritanserin (1.25-5.0 mg/kg) and the 5-HT3 antagonists ondansetron (0.01-1.0 mg/kg) and granisetron (0.5-1.0 mg/kg) failed to alter ethanol consumption. The effect of ipsapirone treatment on ethanol intake was more pronounced in high-preferring animals than in low-preferring. A closer look at the microstructure of the rat's drinking behaviour by means of a microcomputer controlled data acquisition system showed that ipsapirone treatment caused a significant decrease in the number of licks recorded at the ethanol-containing bottle and a decrease in the time spent at this bottle. Furthermore, ipsapirone treatment caused a significant increase in the number of breaks in licking behaviour recorded at this bottle. The drinking behaviour at the water-containing bottle was not affected by the ipsapirone treatment. Neither was the rat's eating behaviour altered by this treatment. These findings support the hypothesis that the 5-HT system is involved in the regulation of ethanol intake, with special emphasis on the involvement of the 5-HT1A receptor subtype, and may indicate that central reward-mediating mechanisms are influenced. PMID- 8507392 TI - Recognition of food in weanling rats exposed to alcohol prenatally. AB - Offspring of rats fed a liquid diet containing ethanol during their pregnancies were compared to controls on a caloric discrimination test beginning at 22 days of age. All pups received simultaneous choice between a palatable, noncaloric diet and a similar diet containing starch. Each diet contained a distinctive flavor. To test for flavor preference learning, pups then received an extinction test: a simultaneous choice between two noncaloric diets, identical except for flavor. Prenatal alcohol exposure had no substantial effect on the caloric discrimination, and all groups preferentially ingested the starch diet on all test days. However, during the extinction test, alcohol-exposed pups showed a significantly weaker flavor preference than control pups. These data extend the effects of prenatal alcohol exposure on learning and ingestive behavior to include solid food discriminations at the time of weaning. PMID- 8507393 TI - Inotropic effects of ethanol on the isolated papillary muscle of the diabetic rat. AB - The present study was designed to characterize the inotropic effects of ethanol (ETOH) on diabetic rat heart. Left-ventricular papillary muscles, from normal and diabetic (streptozotocin, 50 mg/kg IV; 6 weeks) rats, were superfused with Tyrode's solution at 30 oC while driven at 0.5 Hz. Developed tension, time-to peak tension (TPT), time-to-90% relaxation (RT90), maximum rate of tension developed (+VT) and maximum rate of tension fall (-VT) were determined in the absence and presence of clinically relevant concentrations of ETOH (80-240 mg/dl, i.e., 1.7-5.2 mM). Ethanol decreased developed tension, TPT, RT90, and VT in papillary muscles from both groups. Ethanol 80 mg/dl reduced tension, +VT and -VT in preparations from diabetic animals. However, this concentration had no effect on normal muscles. An intermediate concentration of ETOH (120 mg/dl), decreased tension and +VT in preparations from both groups, whereas a higher dose (240 mg/dl) decreased tension, TPT, RT90, VT, and -VT, and induced spontaneous contractures in both groups. The negative inotropic effects of ethanol were generally concentration-dependent and the diabetic myocardium maybe more sensitive to inotropic effects of clinically relevant concentrations of ETOH. Ethanol-induced diminution in contractile tension in normal and diabetic myocardium is associated with reduced contraction and relaxation velocity as well as their respective duration. PMID- 8507394 TI - Rat offspring sired by males treated with alcohol. AB - Male rats were intubated twice daily with either 2 or 3 g/kg of alcohol for nine weeks and were then bred to untreated females. Control animals were intubated with vehicle (distilled water). Controls and 2-g/kg males were pair-fed to 3-g/kg males. A fourth group served as a nonintubated, ad lib control. Male fertility was not affected by alcohol. Mean birth weights were not affected by paternal alcohol treatment, but there was a significant increase in the number of "runts" (< 5.5 g at birth) in the 3-g/kg paternal group. There was also a decrease in the percent of males per litter sired by alcohol-treated fathers. Adrenal weights were increased at birth and spleen weights were decreased at 21 days of age in these offspring as well. These results indicate the potential of paternal alcohol consumption for significantly altering stature and organs in offspring. PMID- 8507396 TI - Phylogeny of B-cell development. AB - All vertebrates with jaws (Gnathostomata) have B cells. With the exception of some B cells in cartilaginous fish that express germ-line joined Ig genes, all B cells, irrespective of the organization of their Ig genes (which varies among vertebrates), rearrange the Ig-gene segments somatically. Somatic diversification occurs in all species during rearrangement (junctional diversity) and later by somatic mutation of gene conversion. Somatic mutants are poorly selected in species that lack germinal centers, which may explain the differences in antibody repertoire among vertebrates. The early (larval or neonate) B-cell repertoire is restricted in all species so far studied because of a lack of N-region diversity and in some cases because of a special usage of the D segments of the heavy chain genes. PMID- 8507395 TI - Alcohol drinking in rats is attenuated by the mixed 5-HT1 agonist/5-HT2 antagonist FG 5893. AB - Over the last three decades, the neurotransmitter serotonin (5-HT) has been implicated in the etiological mechanisms underlying the excessive drinking of ethyl alcohol. Recently, the 5-HT2 antagonist amperozide was found to reduce selectively the high intake of alcohol in the cyanamide-induced drinking rat without any adverse side effects. The purpose of the present study was to determine the action on alcohol drinking of the novel second-generation amperozide-like drug, which is a mixed 5-HT1 agonist/5-HT2 antagonist, FG 5893 (2 [4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-pyridinecarb oxylic acid methyl ester). To induce preference for alcohol in Sprague-Dawley rats, the enzyme aldehyde dehydrogenase was inhibited by cyanamide administered in the absence of alcohol in a dose of 10 mg/kg twice a day over three days. A standard three-bottle preference test was used in which water and a maximally preferred concentration of alcohol were offered to each animal. Following control tests of alcohol preference for 3 days, either a saline control vehicle or FG 5893 in a dose of 0.5, 1.0, or 2.5 mg/kg was administered subcutaneously at 1600 and 2200 for 3 consecutive days. Whereas control injections of saline were without effect on alcohol consumption, all doses of FG 5893 significantly reduced the 24-h intake of alcohol in terms of both absolute g/kg and proportion of alcohol to total fluid intake. Further, the 1.0 and 2.5 mg/kg doses of FG 5893 continued to suppress alcohol consumption over two 4-day tests immediately following the injection sequence and after a 40-day interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507397 TI - Gene rearrangement and B-cell development. AB - The differentiation of B lymphocytes from their progenitors progresses through a series of successive stages that are defined by sequential rearrangement of Ig loci and surface expression of various stage-specific markers, including Ig heavy and light chain proteins. Considerable evidence suggests that the appearance of cells with an orderly progression of Ig gene rearrangements is linked to the expression of the rearranged Ig gene products. Recent experiments have clarified our understanding of mechanisms by which rearrangement of Ig gene segments is controlled and how Ig gene products participate in the regulation of the B-cell differentiation program. PMID- 8507398 TI - Generation and regeneration of cells of the B-lymphocyte lineage. AB - B lymphopoiesis in the mouse and in man can be divided into two phases, one in which the compartments of the B lineage are filled with cells, and a second in which these compartments are maintained by regeneration, turnover and selection. Once the immune system has been built it contains around 5 x 10(8) and 10(12) cells of the B-lymphocyte lineage in the mouse and in man, respectively, of which nearly 10 per cent are precursors that are active in regeneration, whereas over 90 per cent are resting, mature B cells. PMID- 8507399 TI - Somatic mutation and memory. AB - The germinal center plays a crucial role in the development of the memory B cell. The repertoire of the antigen-specific B cell is shaped in this microenvironment. Self-specific B cells escaping normal regulation may develop into high affinity pathogenic Ig-producing cells. PMID- 8507400 TI - CD4, CD8 and tyrosine kinases in thymic selection. AB - Analysis of T-cell development in transgenic and gene-deficient mice suggests that the co-receptor function of CD8 is essential for positive selection. Recent data also demonstrate that the requirement for CD4 and CD8 in negative selection of T cells is not absolute and may be regulated by T-cell receptor affinity for the deleting ligand, an interpretation consistent with the affinity model of thymic selection. In addition to its association with CD4 and CD8, it appears that p56lck is also important during the early stages of thymic development. PMID- 8507401 TI - Gut intraepithelial T lymphocytes. AB - The gut mucosa, given its length, contains a very large number of T lymphocytes in the Peyer's patches and disseminated all along the mucosa. The most conspicuous element of this last compartment, the gut intraepithelial lymphocytes, represents a population of CD8+ T lymphocytes as large as that found in the largest lymphoid organ, the spleen. In spite of their numerical importance and the fact that they are in the immediate vicinity of the largest permanent antigenic stimulus in the whole organism, these cells have remained for a long time, paradoxically, the least understood of the lymphocyte populations, in their ontogeny and physiological role. It is becoming increasingly apparent that they are ontogenically more complex than the bulk of the T lymphocytes present in the lymphoid organs and are probably able to recognize a larger array of antigenic determinants than the peripheral CD8+ T lymphocytes. PMID- 8507402 TI - Immunological techniques. PMID- 8507403 TI - Bacterial expression of immunoglobulin fragments. AB - The expression of Ig fragments in Escherichia coli permits rapid access to engineered molecules with antigen-binding properties. While the expression in a functional state by secretion to the periplasm is the standard method for the production of Fv and Fab fragments, single chain Fv fragments are mainly produced by refolding from insoluble aggregates. Although all of these Ig fragments serve as valuable aids in the study of antigen binding, their different biochemical properties must be considered when using them as research tools or for medical applications. In addition to these simple univalent antibody fragments, the bacterial expression of bivalent and bispecific versions and of hybrid proteins with novel effector functions is gaining increasing importance. PMID- 8507404 TI - Production of human antibodies using bacteriophage. AB - The immune system produces antibodies by a process of antigen-driven selection. An in vitro process of antigen-driven selection, based on the display of antibody fragments on filamentous bacteriophage, has recently been developed. This enables human antibody fragments of high affinity and specificity to be produced without immunization. PMID- 8507405 TI - Engineered bacterial receptors in immunology. AB - Gram-positive surface receptors, such as staphylococcal protein A ans streptococcal protein G, have been genetically engineered for many applications in the field of immunology, including detection antigens, affinity purification of fusion proteins and display of heterologous epitopes on the surface of bacterial cells. PMID- 8507406 TI - Methods for measurement of antibody/antigen affinity based on ELISA and RIA. AB - Various enzyme-linked immunosorbent assay or radioimmunoassay methods are currently used to quantify the antibody-antigen interaction. Only those based on indirect competition--enzyme-linked immunosorbent assay or radioimmunoassay--can provide the real thermodynamic affinity of the antibody for its antigen. They can be applied to a variety of experimental situations, some of which are reviewed here. PMID- 8507408 TI - Lymphocyte development. PMID- 8507407 TI - Surface plasmon resonance for detection and measurement of antibody-antigen affinity and kinetics. AB - Kinetic and affinity information on biospecific interaction can be generated by analysis of adsorption of analyte to immobilized ligand on a sensor based analytical system. The analysis can be performed free of label and directly using culture supernatants. It was found to be particularly valuable for analysis of antibody-antigen interactions. PMID- 8507409 TI - Immunological techniques. PMID- 8507410 TI - Drug interactions with zidovudine. PMID- 8507411 TI - Antigenic variation of the dominant gp41 epitope in Africa. AB - OBJECTIVE: To determine the value of (combinations of) synthetic peptides representing immunodominant sites on HIV-1/HIV-2 transmembrane proteins for the detection and discrimination between HIV-1 and HIV-2 infection in various populations. DESIGN AND METHODS: Two 24-mer synthetic peptides derived from immunodominant sites on the HIV-1 and HIV-2 transmembrane proteins were used separately, in combination (env 1/2), and in combination with recombinant p24 (p24/env) in enzyme-linked immunosorbent assays. RESULTS: Positive reactions with env-1 were found in 150 out of 150 (100%) samples from Dutch AIDS patients, 60 out of 60 (100%) samples from Dutch homosexual men obtained 1 year after HIV-1 antibody seroconversion, 29 out of 30 (96.7%) samples from these men obtained at the time of HIV-1-antibody seroconversion, 40 out of 41 (97.6%) samples from East Africans with AIDS-related symptoms, and three out of 29 (10.3%) samples from West Africans with HIV-2 infection (including a sample from an individual infected with both HIV-1 and HIV-2). Positive reactions with env-2 in these study populations were 11 out of 150 (7.3%), nine out of 60 (15%), none out of 30 (0%), 25 out of 41 (60.9%) and 29 out of 29 (100%), respectively. In the samples with dual reactivity, true versus cross-reactivity could generally be differentiated on the basis of large differences in optical density values in the respective assays. All samples reacted positively with p24/env; 308 out of 310 (99.3%) were positive in the env 1/2 assay. Four East African samples that had negative or only weakly positive reactions with env-1 showed a noticeably stronger reaction with variant peptides derived from Central African isolate sequences. In all samples from HIV-1-infected Dutch homosexual men, the strongest signal was detected using the env-1 peptide sequence, which is derived from European and American isolates. CONCLUSIONS: Small peptide antigens may permit the detection of strain-specific antibodies, allowing serological characterization of HIV isolates. PMID- 8507412 TI - Greater diversity of the HIV-1 V3 neutralization domain in Tanzania compared with The Netherlands: serological and genetic analysis. AB - OBJECTIVE: To compare variation in the HIV-1 V3 neutralization domain in Tanzania and The Netherlands. METHODS: For serologic analysis, the specificity of anti-V3 antibodies (immunoglobulin G) for a panel of V3 peptides was determined in sera from 55 symptomatic HIV-1-infected Tanzanians and 51 Dutch AIDS patients. For genetic analysis, viral RNA was isolated from 15 of the Tanzanian sera and six of the Dutch sera. The V3 encoding region was reverse-transcribed, polymerase chain reaction-amplified and bacterially cloned, and sequences were determined over a stretch of at least 207 nucleotides. RESULTS: Thirty-five per cent of the Tanzanian sera, versus 2% of the Dutch sera, showed the highest reactivity to a V3 sequence of Zairian origin (RKSIHVGPGQAFYATG). Twenty-nine per cent of the Tanzanian sera, versus 82% of the Dutch sera, showed the highest reactivity to V3 sequences of US/European origin (RKSIXIGPGRAFYTTG; X = H, P or N). The Tanzanian RNA sequences showed greater diversity (mean distance, 19%) than the Dutch RNA sequences (10%). The measured anti-V3 specificities of the Tanzanian sera did not match accurately with the V3 sequences recovered from these sera. However, reactivity to the Zairian V3 peptide was associated with the sequence GPGQ, found in the centre of the V3 in 50% of the Tanzanian sequences. Sera from both countries that showed similar reactivities to the peptide panel contained RNA sequences that were relatively distant. CONCLUSIONS: The diversity of the HIV-1 population in Tanzania is much greater than that in The Netherlands. An indication of the HIV-1 V3 variation in a particular geographic region can be obtained by serological methods, but sequence analysis should not be omitted. PMID- 8507413 TI - Cost-effective diagnosis of HIV-1 and HIV-2 by recombinant-expressed env peptide (566/996) dot-blot analysis. AB - OBJECTIVE: To characterize the recombinant env peptides, 566 (HIV-1) and 996 (HIV 2), for their ability to serodiagnose HIV-1 and HIV-2 infection. To develop a cost-effective dot-blot format for these peptides, and to evaluate its performance in a developing country laboratory. DESIGN: The recombinant env peptides were evaluated using a select panel of sera (n = 327) with known serostatus from geographically diverse areas. A dot-blot assay was developed and tested on a second set of immunoblotted sera (n = 331) and further evaluated in the field on a third set of sera (n = 2718) from study populations. METHODS: All sera were evaluated by immunoblot with both HIV-1 and HIV-2 viral lysates. The recombinant env peptides were characterized in immunoblot assay before development of the dot-blot assay. RESULTS: The 566 (HIV-1) peptide showed 100% sensitivity and specificity. The 996 (HIV-2) peptide performed similarly, but showed the presence of HIV-1 cross-reactive epitopes. When the two env peptides were used together, there was high specificity and sensitivity for detecting HIV positive sera in both immunoblot and dot-blot formats. The dot-blot assay performed in the field showed slightly lower specificity and sensitivity for HIV diagnosis. The relative cost of this assay combined with non-commercial immunoblot confirmation was 10-fold lower than conventional commercial assays. CONCLUSIONS: The 566 and 996 env peptides are appropriate antigens for HIV serotype diagnosis. A dot-blot assay using these peptides may be a useful cost effective method for HIV diagnosis applicable in developing country laboratories. PMID- 8507414 TI - Accurate detection of maternal antibodies to HIV in newborn whole blood dried on filter paper. AB - OBJECTIVE: The testing of neonatal blood specimens dried on filter paper for maternal HIV antibodies, using an enzyme immunoassay (EIA) with confirmation of repeatedly reactive specimens by immunoblot (IB), was first described in 1987. It has been used to conduct large, unlinked, anonymous HIV seroprevalence surveys for surveillance of HIV in child-bearing women in several countries. We directly assessed the sensitivity and specificity of this combination of tests to detect maternal HIV antibodies. SETTING: Serum samples obtained from mothers delivering at a major hospital in Kinshasa, Zaire were screened for HIV antibody using the rapid assay HIVCHEK. DESIGN: Plasma from HIVCHEK-positive women and age-matched negative controls were tested by enzyme-linked immunosorbent assay (ELISA); repeatedly reactive specimens were confirmed by Western blot (WB). Two days after delivery, whole blood was obtained from each newborn by heel-stick, dried on filter paper, and tested by EIA. Repeatedly reactive specimens were confirmed by IB. MAIN OUTCOME MEASURE: The serologic status of neonatal filter-paper specimens was compared with that of corresponding maternal plasma. RESULTS: The testing of neonatal filter-paper specimens using EIA, with confirmatory testing of repeatedly reactive specimens using IB, was 100.0% sensitive [of the 192 ELISA positive and WB-positive maternal plasma specimens, 192 of the corresponding newborn filter-paper specimens were EIA-positive and IB-positive; 95% confidence interval (CI), 98.1-100]. The detection of maternal HIV antibodies was 99.6% specific using this combination of tests (of the 281 ELISA-negative or ELISA positive but WB-negative maternal plasma samples, 280 of the corresponding newborn filter-paper specimens were EIA-negative or EIA-positive but IB-negative; 95% CI, 98.0-100). CONCLUSIONS: Maternal HIV antibodies can be detected accurately by testing neonatal blood dried on filter paper, using EIA with confirmation of repeatedly reactive specimens by IB. This approach can facilitate the determination of HIV seroprevalence in child-bearing women in countries with neonatal screening programs, or where serum or plasma is difficult to obtain. PMID- 8507415 TI - Cell surface proteins binding to recombinant soluble HIV-1 and HIV-2 transmembrane proteins. AB - OBJECTIVE: To further characterize cell surface proteins binding to recombinant soluble (rs) forms of the transmembrane glycoproteins gp41 of HIV-1 (rsgp41) and gp36 of HIV-2 (rsgp36). METHODS: Various human and murine cell lines of different lineages were surface-labelled with 125I. rsgp41 and rsgp36 were bound to CnBr Sepharose and used as an affinity matrix for the surface-labelled cell lysates. The bound cell surface proteins were separated on sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions. A rabbit serum was produced against one of the cell surface proteins and flow cytometry used to compare the results with those obtained from affinity chromatography. RESULTS: We have confirmed and extended the results obtained by Qureshi et al. [1]. In addition to the 44kD protein, we identified cell surface proteins with molecular weights of 98 and 106 kD binding with high affinity to both rsgp41 and rsgp36. We have demonstrated differences between human and murine cell lines in the expression of the cell surface proteins that interact with rsgp41 and rsgp36. Furthermore, a correlation between the level of rsgp41 and rsgp36 binding proteins, detected either by affinity chromatography or by reactivity with an antiserum directed against one of the cell surface binding components was shown. CONCLUSIONS: Three cell surface proteins, with molecular weights of 44, 98 and 106 kD, bind with high affinity to rs forms of gp41 and gp36. Their expression decreases from a T-lymphoid cell line, to a monoblastoid cell line, to a cell line representing mature monocytes. Human T-cell lymphotropic virus-infected cell lines show a predominance of the 44 kD protein. There are species-specific differences, in that murine cell lines lack the 44 kD protein. PMID- 8507416 TI - Progression to AIDS in French haemophiliacs: association with HLA-B35. AB - OBJECTIVE: To evaluate whether HLA-B35 influences progression to AIDS in HIV seropositive subjects with haemophilia. DESIGN: Retrospective (before 1985) and prospective (after 1985) follow-up of a group of French haemophiliacs. METHODS: We studied 144 seropositive patients with moderate or severe haemophilia A or B or von Willebrand's disease. Enzyme-linked immunosorbent assay was used to screen patient sera for total HIV antigen and core p24 antigen antibodies. All patients were typed for HLA A, B and C antigens in the same laboratory. Time of seroconversion was estimated to be the mid-point between the last seronegative test and the first seropositive test. AIDS-free survival curves were constructed using the Kaplan-Meier estimate and differences in survival analysed using the Mantel-Cox test. The Cox proportional hazards model was used to adjust for confounding variables. RESULTS: Median follow-up after seroconversion was 8.7 years (range, 3.5-10.7 years). By the end of the study, six HLA-B35-positive patients and 12 HLA-B35-negative patients had progressed to AIDS. Individuals with HLA-B35 showed a significantly faster rate of progression to AIDS over the follow-up period than HLA-B35-negative individuals (hazard ratio, 2.72; P = 0.037). After adjusting for type and severity of haemophilia, CD4 cell count at first seropositive test, age at seroconversion, and zidovudine treatment before AIDS, the hazard ratio was 2.74 (P = 0.045). CONCLUSION: HLA-B35 is a risk factor for more rapid progression to AIDS in subjects with haemophilia. PMID- 8507417 TI - Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients. AB - OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000 bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well. PMID- 8507418 TI - Neuropsychological performance in symptomatic and asymptomatic HIV infection. AB - OBJECTIVE: To examine cognitive function in patients at various stages of HIV infection, and to determine the nature and severity associated with stage of illness. DESIGN: Subjects were administered an extensive battery of neuropsychological tests. SUBJECTS: Two hundred and thirty-three HIV-1-infected homosexual/bisexual men and 77 HIV-negative control subjects who had been screened for previous neurological illness. All subjects were volunteers in a longitudinal study of neurobehavioral complications of HIV infection. RESULTS: Patients with symptomatic infection differed from controls on a large number of measures, and asymptomatic patients had a more circumscribed pattern of deficit. On a summary measure of cognitive impairment, there was a twofold increase in the prevalence of impairment in asymptomatic patients relative to controls, and a fourfold increase in symptomatic patients. Memory and dexterity problems appear to be early features of neurobehavioral dysfunction, and frontal lobe deficits were found in patients with symptomatic infection. CONCLUSION: These data indicate that there is a steady increase in the prevalence of neurobehavioral abnormalities associated with stage of infection. The pattern of abnormality also varies with disease stage. PMID- 8507419 TI - Economic impact of the AIDS epidemic in the European Community: towards multinational scenarios on hospital care and costs. AB - OBJECTIVE: To underpin multinational public-health HIV/AIDS strategy planning in the European Community (EC) by integrating national studies on HIV/AIDS in scenario analysis. METHOD: Three types of data are used: routine surveillance data, information on disease progression and observational studies on the economic impact. The HIV/AIDS epidemic is simulated using two models (MIDAS and PC-Based AIDS Scenarios). Selected simulations, consistent with surveillance data, are connected to economic impact (hospital-bed needs and annual hospital costs for AIDS patients). Parameter values expressing per person-year economic impacts are derived from a structured review of publications on economic aspects of AIDS. RESULTS: Evaluation of published studies on hospital resource use and costs in EC countries shows that there are significant differences between both countries and studies, even after conversion to similar measures (for example, using purchasing power parities). These differences are partly due to factors such as the composition of the patient population. Differences in methodology may also have influenced the results. Economic impact is analysed for combinations of three factors; survival time after AIDS diagnosis, hospital inpatient days needed per person-year and corresponding hospital costs per person-year. All scenarios indicate 1995 hospital-bed needs above the 1990 level of 5400 beds. Hospital cost projections for 1995 vary (up to US$1050 million). CONCLUSIONS: (1) For economic impact assessment, there are important gaps in epidemiological and economic data, and in the methods for linking these. (2) Standardization of studies on the resource use and costs of HIV/AIDS is necessary to provide a sound basis for multinational scenarios. (3) Preliminary multinational scenarios show that by 1995 hospital-bed needs for AIDS might reach 0.45% of all hospital beds available in the EC, and that hospital cost projections for AIDS in that year will range from 0.15% to 0.30% of EC health-care expenditure. PMID- 8507420 TI - Patient use and assessment of conventional and alternative therapies for HIV infection and AIDS. AB - OBJECTIVE: To investigate the extent of recourse to alternative therapies among 184 HIV-positive patients who continued to attend conventional medical clinics. The study describes the specific alternative therapeutic modalities that were more commonly sought by our respondents, and provides data on the subjective assessment of the efficacy of both conventional and alternative therapies. METHODS: Demographic and behavioral information were obtained from standard, self administered, anonymous questionnaires distributed at three HIV clinics in the Philadelphia area. RESULTS: Forty per cent of patients reported having used alternative or complementary therapies. Forty-two per cent of respondents who had been enrolled in clinical trials had used alternative therapies at some stage. Recourse to such therapies was significantly associated with risk-group affiliation, duration of seropositivity, and sex. The decision to use alternative therapies was not significantly related to age, race, education, religion or severity of symptoms. Of respondents using alternatives, 10% expected the unconventional treatments to cure their HIV infection, and 36% expected them to delay the onset of symptoms. CONCLUSION: The results of this study will contribute to conventional practitioners' understanding of those unconventional explanations and therapies for HIV infection that many patients find relevant and meaningful. Health-care workers should be aware of their patients' interest in participating in decisions about their treatment--whether alternative or conventional--and be prepared to work with them to achieve satisfactory outcomes. PMID- 8507422 TI - Testing practices and spread of HIV among sexual partners of HIV-positive haemophiliacs in Italy. Gruppo Italiano Coagulopatie Congenite. AB - OBJECTIVES: To evaluate rates and predictors of testing and HIV positivity among the sexual partners of Italian HIV-positive haemophiliacs. METHODS: Our index cases were 602 sexually active HIV-positive haemophiliacs (aged 18 years or more) enrolled in the Italian Registry of Haemophilia. Data on the demographic and clinical status of the haemophiliacs, whether their partners had undergone HIV testing, and the results of these tests were collected. RESULTS: To date, 205 (34.1%) partners of HIV-positive haemophiliacs have been tested for HIV, of whom 27 (13.2%) were seropositive. On univariate analysis, haemophiliacs who were unmarried, younger, and asymptomatic were less likely to have partners who had been tested for HIV (P << 0.001). On multivariate analysis, unmarried status [odds ratio (OR), 8.4; 95% confidence interval (CI), 5.4-13.1; P << 0.001] and younger age (OR, 1.9; 95% CI, 1.1-3.2) again predicted a higher rate of non tested partners. There was no association between the demographic and medical characteristics of HIV-seropositive haemophiliacs and the risk of HIV positivity among their sexual partners. CONCLUSION: This study demonstrates that a high proportion of sexual partners of HIV-positive haemophiliacs have not yet been tested for HIV. The single most important predictor of not being tested was the marital status of the index case. These results emphasize the need to strengthen prevention programmes aimed at minimizing the risk of heterosexual HIV transmission, particularly among younger unmarried haemophiliacs. PMID- 8507421 TI - Sentinel surveillance for HIV-1 infection: how representative are blood donors, outpatients with fever, anaemia, or sexually transmitted diseases, and antenatal clinic attenders in Mwanza Region, Tanzania? AB - OBJECTIVE: To assess the validity of extrapolation from sentinel data by comparing the HIV-1 prevalence of various sentinel groups with that of the general population in Mwanza Region, Tanzania. METHODS: In a population survey, 4161 individuals were selected in a stratified random cluster sample. Sentinel groups (all in the age group 15-54 years) included blood donors (n = 1090); patients examined at district hospitals for the presence of malaria parasites (n = 1488), anaemia (n = 1339), or syphilis (n = 33); and antenatal clinic attenders (n = 1193). The HIV-1 serostatus of individuals selected from the population survey was tested using enzyme-linked immunosorbent assay (ELISA) and Western blot; 51% of the blood donors were tested using HIVCHEK, and all others using ELISA. HIV-1 prevalence was standardized for age, sex, and urban/non-urban location. RESULTS: HIV-1 prevalence (standardized by age, sex, and residence) in Mwanza Region was 4.0% (3.0% in non-urban areas and 11.3% in town). The standardized HIV-1 prevalences in the sentinel groups were: blood donors, 4.5%; patients with fever, 11.6%; patients with anaemia, 8.9%; urban sexually transmitted disease patients, 27.1%; urban antenatal clinic attenders, 11.8%. The crude prevalence in blood donors was 6.0%. CONCLUSION: Blood donors who are related to blood recipients appear to be a representative sentinel group in this region, provided that data are standardized for age, sex, and urban/non-urban location. Patients with fever and antenatal clinic attenders may reflect trends, but data from patients with fever markedly overestimate, and data from antenatal clinic attenders underestimate, population HIV-1 prevalence. Because self selection of blood donors may become more pronounced, this comparison should be repeated later or elsewhere, should the opportunity arise. PMID- 8507423 TI - Multiple sexual partners: results of a national HIV/AIDS survey in the Central African Republic. AB - OBJECTIVES: To determine the prevalence and characteristics of individuals with more than one sexual partner in the Central African Republic during the previous 12 months. DESIGN: A national survey. METHODS: A stratified sample of 2589 individuals aged 15-50 years was interviewed in late 1989. The 157-question survey questionnaire was a modified version of a questionnaire developed by the World Health Organization Global Programme on AIDS. RESULTS: Thirty-four per cent of men and 17% of women reported having sex with more than one partner during the previous 12 months. For both men and women, logistic regression indicated that the risk of having multiple partners increased with being single compared with being married; being employed in a profession other than agriculture compared with being a farmer, unemployed, a housewife, or a student; living in an urban rather than a rural area; rape being part of their first sexual encounter; and combining sex with alcohol. Risk increased with increasing ability to read for men and with decreasing age and drinking alcohol for women. CONCLUSIONS: These findings can be used to develop and target HIV/AIDS prevention and control programmes and to improve mathematical models of the epidemic. PMID- 8507424 TI - Further observations on zidovudine transfer and metabolism by human placenta. PMID- 8507425 TI - Secreting adrenal carcinoma in an HIV-infected patient. PMID- 8507426 TI - HIV-related ocular microangiopathic syndrome and neuropsychological functioning. PMID- 8507427 TI - Decay of HIV-1 infectivity in whole blood, plasma and peripheral blood mononuclear cells. PMID- 8507428 TI - Clinical manifestation of HIV infection in northern Zaire. PMID- 8507429 TI - Can prescribing policy influence patterns of drug taking and methods of drug administration? PMID- 8507430 TI - Characteristics of spirituality in the lives of women in a rural Appalachian community. AB - The aim of this study was to add to nursing's knowledge base relative to spirituality by exploring how women in rural Appalachia experience and describe spirituality in their daily lives. Data was gathered through participant observation in a small rural community in West Virginia, including in-depth interviews of five women from the community. Characteristics of spirituality included belief in God or Greater Source, prayer/meditation, and a sense of relationship or connectedness with others, nature and oneself. The dominant theme which emerged relative to these relationships was that of self-reliance or inner strength. Spirituality for these women relates to the whole of life and is relational. PMID- 8507431 TI - A transcultural nurse's adventures in Costa Rica: using Leininger's Sunrise Model for transcultural nursing discoveries. AB - This paper is a descriptive report of a transcultural nurse's experiences as an Earthwatch volunteer working with Leatherback sea turtles in Costa Rica. While in Costa Rica the author had an opportunity to observe and experience the culture and lifeways of the people of Costa Rica. The author attempted to discover and understand aspects of the Costa Rican social structure and world view and relate these insights to Leininger's (1991) Sunrise Model and the role of transcultural nurses. Leininger's (1991) Sunrise Model depicted the relationships inherent in her theory and included: culture, world view, and social structure dimensions. The social structure dimensions included: technological, religious and philosophical, kinship and social, cultural values and lifeways, political and legal, economic, and educational factors. The insights and understandings learned through application of Leininger's (1991) Sunrise Model were applied to transcultural nurses' role in meeting the care needs of clients from various cultures. PMID- 8507432 TI - Health care reform: when will it include transcultural nursing care? PMID- 8507433 TI - Influences on the cultural self-efficacy of community health nurses. AB - This paper presents the results of factor and regression analyses conducted on the Cultural Self-Efficacy Scale to determine the underlying conceptual structure, and relationship to demographic variables. The Cultural Self-Efficacy Scale was first used with a sample of 190 community health nurses in Connecticut. It has an estimated total scale internal consistency of .97. In 1988, data were collected to examine cross-cultural self-efficacy of nurses working in a variety of settings, including health departments. The principal factor analysis revealed a four factor structure that is conceptually meaningful. Taken together, the four factors accounted for 90% of the total scale variance. Regression analyses showed significant relationships between perceptions of efficacy and demographic variables of race, education, and experience. PMID- 8507434 TI - Towards conceptualization of transcultural health care systems: concepts and a model. 1976. PMID- 8507436 TI - Strategic planning to prepare transcultural nursing society for the 21st century. PMID- 8507435 TI - Experiential learning: an approach to transcultural education for nursing. AB - Delivery of culturally appropriate health care in our pluralistic society demands that practitioners develop special attitudes, knowledge, and skills. Experimental learning is a powerful methodology for addressing the affective, as well as the cognitive, domain of learning. The exploration of personal values is an essential first step in developing cultural awareness in order to move learners beyond ethnocentrism through awareness, understanding, acceptance, and appreciation of other cultures if learners are to truly adopt a multicultural approach to their professional practice. The nursing curriculum at McMaster University School of Nursing is based on the principles of adult education and self-directed learning. A series of guided experiences have been undertaken with a variety of health sciences learners, both students and faculty members, to foster an increased appreciation of (their) own values preliminary to embarking on knowledge and skill acquisition for transcultural health care. PMID- 8507437 TI - Symposium introduction: aberrant prorenin-renin system behavior in diabetes. PMID- 8507438 TI - The Kidneys, Diabetes Mellitus and Hypertensive Disease. Pathophysiology and Therapeutic Implications. PMID- 8507439 TI - Hypertension and the kidney. PMID- 8507440 TI - Ionic basis of hypertension, insulin resistance, vascular disease, and related disorders. The mechanism of "syndrome X". AB - Great pathophysiological significance has recently been placed on the association of metabolic abnormalities, such as hyperinsulinemia, insulin resistance, obesity, and frank diabetes mellitus, with essential hypertension and coronary artery disease, and the clinical coincidence of these features has been termed "syndrome X." Despite the suggestion that insulin itself mediates this clinical linkage, the specific mechanisms underlying this syndrome remain poorly understood. We have attempted to understand these phenomena at the cellular level, and have investigated the role of cellular mineral ion species such as cytosolic free calcium (Cai), free magnesium (Mgi), and intracellular pH (pHi) in various insulin resistant states, including essential hypertension, obesity, and type II (non-insulin-dependent) diabetes mellitus (NIDDM). Utilizing nuclear magnetic resonance spectroscopic techniques to noninvasively assess intracellular concentrations of these ions, we observed that each of these disease states is characterized, in whole or in part, by common abnormalities of cellular ion metabolism, including elevated Cai levels and suppressed levels of Mgi and pHi. Furthermore, despite the predominant use of red cells as a tissue source, the measured levels of Cai, Mgi, and pHi were closely related to the ambient blood pressure, the degree of cardiac hypertrophy, and to the hyperinsulinemic response to oral glucose challenge. Altogether, these data suggest an integrated "ionic hypothesis" in which the frequent clinical coexistence of hypertension and altered insulin metabolism derives from common abnormalities of cellular ion handling, resulting in excess steady-state levels of Cai, reciprocal depletion of Mgi, and lowered pHi. These cellular ion alterations would be expected to have tissue-specific consequences, appearing in vascular tissue as vasoconstriction and elevated blood pressure, in skeletal muscle and fat as insulin resistance, in pancreatic beta-cells as hyperinsulinemia, and in neural tissue as potentiated neurotransmitter release and increased sympathetic nerve activity. Thus, according to this hypothesis, essential hypertension, insulin resistance, hyperinsulinemia, and NIDDM are in reality different clinical components of what should be better designated as "generalized cardiovascular-metabolic disease" (GCMD). PMID- 8507441 TI - Hypertension in diabetic patients. An overview of interventional studies to preserve renal function. AB - The combination of diabetes mellitus and hypertension increases the chances for progressive renal disorders and ultimately renal failure. Both animal and human studies have investigated this progression, which does not take place in all diabetic patients, but which does inevitably occur in diabetic patients with hypertension or microalbuminuria. In these patients the control of arterial pressure is critical to the preservation of renal function. Certain antihypertensive agents, notably angiotensin converting enzyme inhibitors, verapamil, and diltiazem, seem to combine the required renal and vascular effects most beneficially. This article reviews the research completed so far into these effects. However, long-term studies are needed to consolidate these findings. PMID- 8507442 TI - Cicaprost, a prostacyclin analog, protects renal function in uninephrectomized dogs in the absence of changes in blood pressure. AB - Ten dogs presenting mild chronic renal failure and hypertension after 27 months of uninephrectomy, during which they received a high sodium and high protein diet, were divided in two groups (n = 5) and followed for 15 months. The same diet was maintained and one of the groups received cicaprost treatment. The animals were periodically tested for biochemical and clinical parameters, and at months 0, 3, 6, and 15, glomerular filtration rate and renal plasma flow (RPF) were measured. Renal biopsies were made after 6 months of follow-up. Control group showed a higher thickening of pre- and intraglomerular portions of arteriolar vessels and an enhancement of mesangial matrix when compared with the treated group. Cicaprost also induced a significant elevation in RPF and a significant decrease in filtration fraction. All these findings suggest that cicaprost, an oral stable prostaglandin I2 analog, could have a protective renal effect in this experimental model. PMID- 8507443 TI - Regulation of the human atrial natriuretic peptide gene in atrial cardiocytes by the transcription factor AP-1. AB - The effects of overexpression of individual components of the AP-1 transcription complex (ie, c-fos and c-jun) were examined in neonatal rat atriocyte cultures. Cotransfection of a c-jun expression plasmid together with a test plasmid linking portions of the human atrial natriuretic peptide (hANP) gene promoter to a bacterial chloramphenicol acetyl transferase (CAT) reporter resulted in a dramatic increase in ANP gene promoter activity. This effect appeared to operate through a consensus TPA (phorbol 12-myristate 13-acetate) response element (ie, AP-1 binding site) located approximately 235 base pairs upstream from the start site of transcription. This same TPA response element appears to be responsible for induction of hANP gene promoter activity by the phorbol ester TPA. Cotransfection of the same hANP promoter-CAT reporter constructs with a c-fos expression vector resulted in an unpredicted inhibition of reporter gene expression. This inhibitory activity was localized to the carboxy terminus of the c-fos protein and dominated the more conventional AP-1-dependent activity located elsewhere in the c-fos molecule. These findings suggest potential mechanisms for linking regulatory signals operative at or near the cell surface to the control of transcriptional activity in the cell nucleus. PMID- 8507444 TI - Independent effects of hyperinsulinemia and hyperglycemia on intracellular sodium in normal human red cells. AB - To study the contribution of glucose vis-a-vis insulin in the altered sodium homeostasis of diabetes mellitus, we utilized 23Na-NMR spectroscopy to noninvasively measure intracellular sodium (Nai) in red blood cells of non diabetic, thin, normotensive subjects (n = 9), before and 60, 120, and 180 min after in vitro incubation with elevated glucose (15 mmol/L) and insulin (200 mumol/L) concentrations. Hyperglycemia caused a significant rise in Nai compared to basal values at 60 (9.1 +/- 0.8 to 9.7 +/- 0.8 mEq/L, P < .05), and 120 min (10.0 +/- 0.7 mEq/L, P < .05 v basal). Hyperinsulinemia induced a more pronounced and prolonged elevation of Nai. Significant elevations occurred at 60 (8.0 +/- 0.5 to 10.2 +/- 0.7 mEq/L, P < .05), 120 (10.5 +/- 1.1) mEq/L, P < .05 v basal), and 180 (9.1 +/- 0.5 mEq/L, P < .05 v basal) minutes. Thus, both hyperinsulinemia, and to a lesser extent, hyperglycemia cause intracellular sodium accumulation in normal human red cells. Since glucose transport in red cells is not insulin-dependent, insulin and glucose presumably exert their effects independently. Altogether, we suggest that these insulin- and glucose mediated effects on cellular sodium, if present in other tissues as well, may underlie the increased total body sodium and the salt-dependent hypertension characteristic of chronic diabetic or hyperinsulinemic syndromes. PMID- 8507445 TI - Divergent effects of acute and chronic ethanol exposure on contraction and Ca2+ mobilization in cultured vascular smooth muscle cells. AB - In cultured rat vascular smooth muscle cells (VSMC), acute preincubation of 100 mmol/L ethanol for 30 min attenuated the number of contracting cells in response to (10(-7) mol/L) arginine vasopressin (AVP) (P < .01). In contrast, VSMC cultured chronically for 3 days in medium supplemented with 100 mmol/L ethanol enhanced (10(-7) mol/L) AVP-induced shape change (P < .01). Specific 3H-AVP binding to VSMC after acute or chronic exposure to 100 mmol/L ethanol did not differ from those of control experiments. Acute ethanol pretreatment attenuated basal, 10(-7) mol/L AVP-, 65 mmol/L K(+)-stimulated Ca2+ uptake, in a dose dependent manner. In contrast, 100 mmol/L ethanol for 4 days enhanced the (P < .001) AVP- 10(-7) mol/L and (P < .01) 65 mmol/L K(+)-stimulated 45Ca2+ uptake. Acute ethanol exposure inhibited and chronic ethanol administration enhanced Ca2+ uptake stimulated by 6 x 10(-7) mol/L Bay K 8644, an activator of voltage sensitive Ca2+ channels. Nifedipine, a blocker of these Ca2+ channels, diminished AVP-stimulated (P < .02) and K(+)-induced (P < .001) Ca2+ uptake more potently in VSMC pretreated for 4 days with 100 mmol/L ethanol than in control cells. Acute ethanol preexposure for 30 min attenuated AVP-stimulated inositol trisphosphate (IP3) formation (P < .05) and the rise in cytosolic free Ca2+ ([Ca2+]i) (P < .01). In contrast, chronic ethanol-treated VSMC enhanced IP3 formation (P < .05) and the rise in [Ca2+]i (P < .01) in response to AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507447 TI - Left ventricular mass and geometry in patients with established hypertension and white coat hypertension. AB - This study was designed to compare the cardiac mass and geometry in white coat hypertensive patients and established hypertensive patients through the prospective comparison of office blood pressure, daytime ambulatory blood pressure, and echocardiographically determined left ventricular mass and cardiac geometry in consecutive patients. We studied 143 patients from general practice in an outpatient hypertension unit. The patients had newly diagnosed mild-to moderate hypertension prior to the institution of pharmacological anti hypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 90 had a consistently elevated diastolic blood pressure (established hypertension), whereas 53 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). Left ventricular mass index was significantly higher in the group with established hypertension, 102.4 +/- 26.6 g/m2 (mean +/- SD) v 93.6 +/- 23.5 (P = .045). Relative wall thickness was likewise significantly higher, 0.36 +/- 0.07 v 0.33 +/- 0.06 (P = .004). There was no significant difference in left atrial dimension. In a multiple regression model the ambulatory measurements and not the office measurements were statistically significantly associated with the extent of cardiac hypertrophy. Further, 44/53 (83%) of the patients with white coat hypertension had normal left ventricular dimensions, versus only 55/90 (61%) of the patients with established hypertension (P = .033). Thus, white coat hypertensive patients display less cardiac involvement than patients with established hypertension, indicating that they should rather be treated as normotensives than as hypertensives, ie, not with pharmacological antihypertensive therapy. PMID- 8507446 TI - Octreotide, a somatostatin analog, reduces insulin secretion and increases renal Na+ excretion in lean essential hypertensive patients. AB - The influence of insulin on renal Na+ excretion is still subject to debate. In order to evaluate the effect of insulin suppression on Na+ excretion, 20 never treated essential hypertensive men and 8 normotensive men were studied. All subjects had a body mass index < 27 kg/m2. Both the glucose and the lipid metabolisms were normal. After 2 weeks under normal NaCl intake (120 mEq NaCl daily), either octreotide, a somatostatin analog, or vehicle were infused in a forearm vein during acute volume expansion (0.30 mL/kg/min isotonic saline given intravenously over a period of 30 min). A double-blind randomized cross-over design was followed, and each subject was given both infusions at a 1 week interval. Blood and urine samples were taken at times--60, 0, 30, 60, 90, 120, 180, 240, and 300 min. Our data showed that octreotide significantly lowered insulin levels in both hypertensives (from 12.2 +/- 2.4 microU/mL at time 0 to undetectable values at time 30 and 60 min) and normotensives (from 11.5 +/- 2.8 microU/mL at time 0, to undetectable values at time 30 and 60 min). Compared to saline infusion alone, octreotide significantly increased Na+ excretion in both hypertensives and normotensives (saline + octreotide v saline alone = P < .05 at time 60 and 90 min). In conclusion, octreotide enhanced the natriuretic response to intravenous Na+ load in both hypertensives and normotensives. The increase in urinary Na+ was accompanied by a significant decrease in plasma insulin levels. PMID- 8507448 TI - Hydrocortisone-induced hypertension in men. The role of cardiac output. AB - In previous studies we have shown that administration of 200 mg/day hydrocortisone (cortisol) to normal subjects raises blood pressure and cardiac output, with no change in total peripheral resistance or resting forearm vascular resistance. We have tested the hypothesis that this rise in cardiac output is essential for the rise in blood pressure (BP). Six normal volunteer men, aged 22 to 34 years, took part in two studies of 10 days, in random order, at least 4 weeks apart. Placebo (Study A) or 50 mg atenolol orally, 12 hourly (Study B), was given on days 1 to 10 and 50 mg cortisol orally, 6 hourly, on days 5 to 10. Blood pressure and cardiac output (Fick technique, alternative Doppler) were measured on days 4 and 10. In Study A (placebo and cortisol) systolic BP rose from 116 to 125 mm Hg (standard error of the difference, SED 1.5), P < .01, and in Study B (atenolol and cortisol) from 109 to 120 mm Hg (SED 1.5), P < .01. Cardiac output (indirect Fick) rose from 4.8 +/- 0.01 to 5.9 +/- 0.2 L/min, P < .01, in A, and was unchanged in Study B, 4.4 +/- 0.1 to 4.4 +/- 0.2 L/min. Cardiac output measured by Doppler method was similar in pattern, 5.1 +/- 0.2 to 6.7 +/- 0.2 L/min (P < .01) in A and 5.7 +/- 0.2 to 5.8 +/- 0.2 in B. Calculated peripheral resistance fell in Study A and increased in Study B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507449 TI - Effects of canrenoate on red cell sodium transport and calf flow in essential hypertension. AB - The effects of potassium canrenoate (100 mg/day, orally for 1 month) on blood pressure, calf blood flow at rest and after ouabain (0.5 mg intravenous bolus), and red cell Na homeostasis were investigated in 15 patients (7 men, 8 women, aged 18 to 63) with essential hypertension and without peripheral vascular diseases. On placebo, acute intravenous ouabain administration significantly and transiently reduced calf flow and increased calf vascular resistance without affecting blood pressure. Canrenoate significantly decreased blood pressure (from 159 +/- 21/105 +/- 9 mm Hg to 141 +/- 14/94 +/- 10, P < .05) and the rise of calf resistance after intravenous ouabain bolus. The latter effect was variable, since it was inhibited almost completely in 8 patients and unaffected in the others. In the patients in whom exogenously administered ouabain was antagonized, canrenoate diminished blood pressure through vasodilation and heightened the red cell Na/K pump. None of these parameters changed significantly in the other patients. Thus these data suggest that the fall in vascular resistance induced by canrenoate is mediated, in part, by the antagonism of endogenous ouabain-like factors. PMID- 8507450 TI - Postpartum abnormalities of carbohydrate and cellular calcium metabolism in pregnancy induced hypertension. AB - We have previously reported that young, primigravid, African-American women who developed preeclampsia exhibited insulin resistance (elevated fasting insulin:glucose ratios) and abnormal intracellular free calcium ([Ca2+]i) metabolism as early as the second trimester of pregnancy. To determine if these abnormalities persist postpartum (suggesting a genetic link), we evaluated the effects of an oral glucose load (50 g) on plasma and glucose insulin, basal platelet [Ca2+]i and platelet [Ca2+]i responses to arginine vasopressin (AVP). The study population consisted of nine, young, primigravid, African-American women at 43 +/- 12 weeks postpartum from pregnancy induced hypertensive (PIH) gestations and 10 age- and weight-matched African-American women who were 29 +/- 7 weeks postpartum from normal pregnancies. The PIH group consisted of five subjects who were preeclamptic and four subjects with gestational hypertension. Baseline fasting body weights, body mass indices, plasma glucose, plasma insulin, basal platelet [Ca2+]i, and platelet [Ca2+]i responses to AVP were similar in the postpartum PIH and control groups. The oral glucose load had no effect on basal platelet [Ca2+]i levels in either group. However, plasma glucose and insulin and platelet [Ca2+]i responses to AVP were accentuated at 30 min following an oral glucose load suggesting a subtle abnormality of carbohydrate and [Ca2+]i metabolism that persists in individuals with pregnancy induced hypertension. Long term studies involving African-American populations will be necessary to determine if these metabolic abnormalities are associated with an increased propensity to hypertension. PMID- 8507451 TI - Red blood cell Na-Li countertransport, hypertensive heredity, and cardiovascular risk in young adults. AB - The erythrocyte Na-Li countertransport (CT) has been considered as a marker of genetic propension to essential hypertension, but also to be linked to atherosclerosis risk factors. We have evaluated these relationships by measuring the Na-Li CT, blood pressure levels, the family predisposition to hypertension, body mass index, subscapular skin-fold thickness, waist/hip ratio, and plasma lipids in 43 young adults (22 to 23 years; 13 with a positive family history of hypertension), followed since adolescence (+/- 10 years) to analyze the natural history of blood pressure in this period of life. The Na-Li CT was negatively correlated with the HDL cholesterol (r = -0.37) and the HDL cholesterol/total cholesterol ratio (r = -0.44). This transport system was positively correlated to family history of hypertension (r = 0.38), waist/hip ratio, and the diastolic blood pressure. When the family history of hypertension was present, Na-Li CT and diastolic blood pressure were higher (P < .05), but the HDL cholesterol was lower (P < .01). After separating people according to the blood pressure level during adolescence in two groups, one lower than the 75th percentile (P75), and one higher, we notice that the latter remains characterized by a higher systolic blood pressure. But neither the Na-Li CT nor family history of hypertension and plasma lipids could explain the difference in the blood pressure behavior during this period. Thus, an increase of RBC Na-Li CT activity in young adults would suggest a higher cardiovascular risk rather than to be a simple marker of a hypertensive risk. PMID- 8507452 TI - Hypertension secondary to chlorpropamide with amelioration by changing to insulin. AB - A retrospective analysis of the records of 22 type II diabetics whose treatment had been changed from insulin to chlorpropamide was performed to investigate the relative effects of insulin and chlorpropamide on blood pressure. Although diastolic BP index was not significantly different between the treatments, systolic BP index was significantly higher on chlorpropamide than on insulin (141 +/- 3 v 135 +/- 3 mm Hg, P = .02). In 10 patients in whom insulin was reinstituted, systolic BP fell significantly (P < .005), suggesting that in type II diabetics chlorpropamide exerts a relative hypertensive effect in comparison to insulin. PMID- 8507453 TI - Cadmium-induced arteriolar constriction in skeletal muscle microcirculation. AB - Cadmium, an environmental pollutant, is known to induce hypertension in animal models, in part via an increase in peripheral vascular resistance. Since prior studies have investigated the vascular effects of cadmium using large, nonresistance arteries, we directly assessed cadmium's action on resistance size arterioles in skeletal muscle using the intact rat cremaster muscle preparation. Cadmium evoked a concentration-dependent constriction of the large arterioles (120 to 50 microns in diameter) but elicited no change in the diameter of smaller arterioles (30 to 15 microns). Blockade of alpha-adrenergic receptors did not diminish the constrictor response of the larger arterioles to cadmium, but bathing the cremaster muscles with a solution containing low calcium attenuated the arteriolar constriction to cadmium. Calcium repletion caused the arterioles to constrict further. These observations provide the first direct evidence that cadmium constricts resistance arterioles in skeletal muscle. The cadmium constriction: (1) is selective for the large arterioles, (2) is not mediated by alpha-adrenergic receptors, and (3) is influenced by the extracellular level of calcium. We conclude that arteriolar constriction in skeletal muscle tissue may play a role in the hypertensive actions of cadmium. PMID- 8507454 TI - SA gene and blood pressure cosegregation using Dahl salt-sensitive rats. AB - Based on the published cDNA base sequence for the (anonymous) SA gene, a polymerase-chain-reaction (PCR) product from the SA gene was obtained from a Dahl salt-sensitive rat kidney cDNA library. Compared to the published sequence, this product had a 102 base pair insert in the 3' end of the cDNA, probably as the result of alternate mRNA splicing. A StuI restriction fragment length polymorphism detected three alleles among various rat strains using this PCR SA gene probe. Alleles at the SA locus strongly cosegregated with blood pressure (P = .0012) in a salt-fed F2 population derived from crossing Dahl S and Lewis rats. In contrast, a cosegregation analysis of blood pressure and SA alleles in salt fed F2 rats derived from a Dahl S x Wistar-Kyoto cross gave a negative cosegregation result. It is concluded that in certain genetic backgrounds the SA gene (or a closely linked gene) can contribute a significant component of genetic hypertension. PMID- 8507455 TI - T cells in reactive arthritis. AB - T cells appear to play a major role in the development, maintenance and also resolution of reactive arthritis (ReA). Recent advances in understanding the processes involved in T cell activation now allow us to examine the peripheral blood and synovial fluid T cell responses to given "arthritogenic" microorganisms in terms of antigen specificity, epitope identification, cytokine secretion patterns, HLA restriction and the role of different T cell subsets in ReA. Peripheral blood bulk proliferation and limiting dilution studies provide evidence that the peripheral T cell response against arthritis-associated gram negative bacteria is decreased in patients developing immunological sequelae such as ReA after gastrointestinal infection. Using clonal analysis of synovial fluid CD4+ T cells it has been shown that a polyclonal rather than an oligoclonal response to a variety of bacterial antigens is induced at the site of synovitis and that these CD4+ T cells produce a Th1-type of cytokine. 65 kD heat shock protein may represent one of the possible linkages of anti-infectious and autoimmune reactions. Furthermore, a spectrum of killer cells is present in the synovial fluid of patients with ReA. This spectrum of cytotoxic T cells includes antigen-specific, class I-restricted alpha beta-TCR+CD8+ lymphocytes, antigen specific, apparently non-MHC-restricted alpha beta-TCR+CD8+ lymphocytes and gamma delta-TCR+ cells with braod cytolytic activity directed against bacteria-infected target cells. HLA-B27-restricted Yersinia- or Salmonella-specific synovial fluid CD8+ T cells may provide the missing link between genetic disposition (HLA-B27) and extra-articular infection with arthritogenic bacteria in these patients. PMID- 8507456 TI - Glycosylation of the major human Pneumocystis carinii surface antigen. AB - It has recently been shown that the major rat P. carinii surface antigen is important for initial host-organism attachment, possibly through binding to fibronectin, mannose-binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook this study to characterize the glycosylation of the major human P. carinii surface glycoprotein (gp95). We have used purified gp95 as a source of antigen, and in lectin binding and deglycosylation studies it was found that approximately 9% of gp95 consists of N-linked carbohydrates of mainly high-mannose and bisected complex-type glycans. Using a polyclonal antibody raised against purified gp95 and crossed affinoimmunoelectrophoresis and the lectins Con A and WGA, gp95 exhibited carbohydrate-dependent microheterogeneity. We therefore suggest that gp95 is composed of subtypes which differ in N-linked glycosylation. PMID- 8507457 TI - Homology between cryptic plasmid from Neisseria gonorrhoeae and genomic DNA from Neisseria meningitidis. AB - The human pathogenic Neisseria species N. gonorrhoeae and N. meningitidis are closely related. In contrast to N. meningitidis, however, almost all clinical isolates of N. gonorrhoeae harbour a phenotypically cryptic plasmid. In some gonococcal strains regions of the cryptic plasmid have been found in the gonococcal genome and it has been suggested that large segments of the cryptic plasmid can be integrated into the gonococcal chromosome of both plasmid-bearing and plasmid-free strains. Here we report homology between parts of the cryptic gonococcal plasmid and genomic DNA from four different N. meningitidis strains from systemic disease isolates in which no plasmids have been found with the applied methods. Serogroup B strains, causing many of the cases of meningococcal disease in Norway, hybridized strongly to the cryptic plasmid probe, in contrast to serogroup A and C strains. Clones hybridizing to the cryptic plasmid were isolated from a meningococcal genomic lambda EMBL3 DNA library and characterized by restriction mapping. When using one such clone as a probe the parts of the cryptic plasmid showing homology to the genomic meningococcal DNA were confined to two small separate regions of 420 and 88 bp. PMID- 8507458 TI - Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats. AB - We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable to the lesions seen in cystic fibrosis (CF) patients. Early transitory IgM titers were demonstrated in both normal and athymic rats. Whilst athymic rats produced much lower IgG titers than the normal rats, presumably due to the absence of CD4+ cells, higher primary IgA titers were achieved. These two models in normal and athymic rats of the chronic lung infection resembling that seen in CF lungs make it possible to study the influence of the various components of the specific and nonspecific defense systems on the course of the chronic P. aeruginosa lung infection and to evaluate the effect of various immunization schedules and immunomodulatory drugs. PMID- 8507459 TI - Postmortem findings and prenatal diagnosis of Zellweger syndrome. Case report. AB - The postmortem findings of siderosis, renal cortical cysts, pachygyria, cortical heterotopia of the brain and cerebellar hypoplasia in a seven-week-old infant with craniofacial dysmorphism and hypotonia prompted the diagnosis of Zellweger syndrome. This was confirmed by analysis of very-long-chain fatty acids in blood spots from filter paper, collected in the neonatal period, and allowed first trimester diagnosis in the subsequent pregnancies. PMID- 8507460 TI - Effect of a human IgG preparation rich in antibodies to a wide range of lipopolysaccharides on gram-negative bacterial sepsis in burned mice. AB - A human intravenous IgG preparation (Anti-LPS IgG) rich in antibodies to different lipopolysaccharides (LPS) and a normal human intravenous IgG (NIgG) were investigated for their ability to confer passive immunity. Both preparations were given at the time of infection (prophylaxis) or during sepsis (therapy) to burned mice with lethal infection induced by various clinically relevant gram negative bacteria. When given at the time of infection both IgG preparations (5 mg/mouse) inhibited lethality induced by some bacteria (Pseudomonas aeruginosa serogroup G and B), but not others (Serratia marcescens, Klebsiella pneumonia, Proteus mirabilis), indicating a protection by by strain-specific antibodies. However, no significant protection was seen when mice were treated during sepsis. The range of specific antibody titers to the whole live bacteria and heat-killed (LPS-preserved) bacteria in the NIgG paralleled that of Anti-LPS IgG; however, the magnitude of the antibody titers did not accurately reflect the protective capacity in vivo. Thus, the exact specificity of the protective antibodies is still unknown. The protective effect of both IgG preparations was dose-dependent; at low IgG doses (0.5 mg/mouse) better protection was obtained with Anti-LPS IgG, whilst at higher doses (> or = 1 mg/mouse) both preparations exhibited identical effects. Low doses of either IgG preparation in combination with subtherapeutic doses of piperacillin significantly enhanced early survival (day 2 for NIgG and day 2 + 3 for Anti-LPS IgG) against P. aeruginosa, but the protective effect waned thereafter. We conclude that a strain-specific antibacterial effect in a compromised mouse infection model can be obtained by early passive immunization with human IgG from large plasma pools. It is suggested that Anti-LPS IgG or NIgG may be of benefit in some cases of gram-negative sepsis when administered as prophylaxis together with proper antibiotic treatment. PMID- 8507461 TI - Location of plasminogen activator (PA) and PA inhibitor in human colorectal adenocarcinomas. AB - Both the coagulation and fibrinolytic cascades generate proteolytic enzymes which appear to be essential for tumor invasion. In the present investigation adenocarcinomas and normal colon from 14 patients with colorectal cancer were studied by immunohistochemistry. The most striking observation was an enrichment of plasminogen activator inhibitor in the tumor tissue, whereas no such immunoreactivity was detected in the biopsies of normal colon. The tumor-host interface was characterized by a massive accumulation of inflammatory cells, macrophages and T lymphocytes. In this area fibrin(ogen) immunoreactivity as a sign of local activation of the coagulation cascade was also seen. The transition zone between the tumor and normal tissue was furthermore characterized by a marked enrichment of urokinase plasminogen activator immunoreactivity. The study strongly indicates that proteases and inhibitors of the fibrinolytic system may be of great importance in tumor invasion. PMID- 8507462 TI - Effect of Legionella pneumophila sonicate on killing of Listeria monocytogenes by human polymorphonuclear neutrophils and monocytes. AB - Legionella pneumophila shares with other intracellular pathogens the ability to resist intracellular killing within phagocytes. An increasing number of cellular components of L. pneumophila are proposed as pathogenic factors of the organism. At the site of infection, the phagocytic cells will be exposed to bacterial components, either expressed on the surface of the organisms or released in the environment upon cell lysis. In this study, we have investigated the effect of water-soluble bacterial components present in L. pneumophila sonicate on the phagocytosis and bactericidal activity of human polymorphonuclear neutrophils and monocytes. Preincubation of neutrophils with L. pneumophila sonicate did not affect phagocytosis of L. monocytogenes, whereas Listeria killing was significantly inhibited at sonicate concentrations of 1 and 2 mg/ml. The phenol phase of a phenol-water extraction, containing most of the lipopolysaccharide (LPS), had no inhibitory effect on the listericidal activity of neutrophils. Killing of Listeria by monocytes was inhibited in a similar manner. The inhibitory activity was mainly recovered in the sonicate fraction above 100 kDa, suggesting that components organized in larger molecular complexes are most likely to represent the inhibitory factors. The inhibitory activity of L. pneumophila sonic extract appears to be related to inhibition of killing mechanisms since uptake of Listeria was not affected by the sonicate. Our observations indicate that as Legionella infection progresses, bacterial components liberated by cell lysis could exert a detrimental effect on the antimicrobial function of phagocytes, stressing the importance of early treatment of Legionnaires' disease to reduce bacterial numbers in the infected tissues. PMID- 8507463 TI - Lack of short-term autoregulation in the cochlear microcirculation in guinea pigs. AB - To determine the relationship between the dynamics of mean arterial blood pressure (MABP) elevation and possible changes in the cochlear microcirculation the cochlear blood flow (CBF) was measured in guinea pigs by a laser Doppler method. The MABP was elevated at rates ranging from 0.02 mmHg/s to 4 mmHg/s by intravenous infusions of norepinephrine or epinephrine in various concentrations. A fall in MABP was induced by exsanguination of the animals. The purpose of the experiments was to record the time of onset and course of an expected autoregulation in the cochlea in response to slow or rapid changes in MABP. The data suggest that there is no short-term autoregulation in the cochlear microcirculation reflecting the increase of the MABP, but a slight compensation occurs when the MABP declines. These latter changes could be attributed to the high CO2 sensitivity of the cochlear blood vessels. PMID- 8507464 TI - Tuberculous tracheobronchial strictures: clinicopathological features and management with the bronchoscopic carbon dioxide laser. AB - Tuberculous tracheobronchial stricture is a rare disease entity at the present time. We report our experiences with carbon dioxide laser treatment for four patients with tuberculous strictures that were resistant to conventional management. All patients were relatively young but were debilitated by the disease. The lesions differed from other forms of benign tracheal strictures as they tended to involve the trachea and right side of the lung and were often multiple. The reasons for this are related to the organism per se and the anatomical arrangement of the tracheobronchial airway. The pathophysiology of tuberculous strictures in the tracheobronchial airway and the technique of bronchoscopic laser resection are outlined. PMID- 8507465 TI - Temporary management of selected pharyngocutaneous fistulas with a silicone septal button. AB - Management of a pharyngocutaneous (PC) fistula following laryngopharyngectomy with or without neck dissection is a difficult problem, particularly in cases where repair cannot be accomplished in a reasonable period of time. Use of a silicone septal button is described in the temporary management of selected PC fistulas (i.e., fistula size not more than 1 cm). This technique has been used successfully to date in three patients whose salivary fistulas were located directly above their stomas. The silicone septal button worked as a useful temporary measure in preventing salivary spillage into the stoma und was well tolerated by the patients treated until definitive closure was possible. PMID- 8507466 TI - Quantification of interleukin-1 in nasal polyps from patients with chronic sinusitis. AB - We have measured interleukin-1 alpha (IL-1 alpha) and beta levels in nasal polyps (NP) from patients with chronic sinusitis (CS) in order to determine their significance in the pathogenesis of NP. NP in ten cases (five male and five female; age range, 17-63 years) were removed to separate mononuclear (M) and polymorphonuclear (PMN) fractions through Ficoll-Paque separation media. ELISA measurements of the M fraction showed that the mean value of IL-1 beta was 17.8 pg/ml per gram, which was significantly higher than that of IL-1 alpha (7.04 pg/ml per gram, P < 0.01, Wilcoxon test). In the PMN fraction, the mean value of IL-1 alpha was 8.79 pg/ml per gram and that of IL-beta was 7.85 pg/ml per gram, which was not significantly different. Mononuclear leukocytes, particularly activated monocytes, seem to be a major source of IL-1 in the NP taken from patients with CS. PMID- 8507467 TI - Squamous cell carcinoma of the base of tongue. AB - Squamous cell carcinoma of the base of tongue is known to have a poor clinical prognosis that is primarily attributable to such tumors usually presenting at an advanced stage. Fortunately, if detected early, these malignancies may have a more favorable prognosis. We have reviewed the current literature of squamous cell carcinoma of the base of tongue, focusing on epidemiologic data, treatment options, as well as survival results. Data have also been incorporated from a previously unpublished retrospective study performed in the Department of Otolaryngology at the University of Pittsburgh. PMID- 8507468 TI - First clinical experiences with an implantable bone conduction hearing aid at the University of Amsterdam. AB - A transcutaneous bone-conduction hearing aid was implanted in 11 patients who were not suitable for transcranial sound amplification. Audiological and surgical selection criteria were followed strictly. One device had to be explanted and minor revision surgery was needed in two cases for skin irritation and scarring. In general the aids were well tolerated but the amplification power of the external device proved to be insufficient in some patients, in whom bone conduction levels were on the borderline of the selection limits. PMID- 8507469 TI - Structure and composition of stereocilia cross-links in normal and hydropic cochleas of the guinea pig. AB - Structure and composition of stereocilia cross-links were investigated cytochemically in normal and hydropic cochleas of the guinea pig. The electron dense markers colloidal thorium and cationized ferritin were used for visualization. Side links as well as tip links were visualized using both markers. Cationized ferritin allowed a better visualization of the delicate cross link substructure than did colloidal thorium. Following digestion with neuraminidase, cross-link reactivity for colloidal thorium was virtually abolished. However, the basic structure of the cross-links could still be observed as a result of routine post-fixation and contrast staining. In both 3- and 6-month hydropic cochleas glycocalyx reactivity of the stereocilia appeared to be unaltered, provided that stereocilia were still present. However, loss of cross-links of the outer hair cells - resulting in disarrangement of the stereociliary bundles - was observed in hydropic cochleas. Our results suggest that cross-links are a separate morphological and cytochemical entity, which is different from the glycocalyx. Furthermore, loss of stereocilia cross-links, with concomitant disarrangement of the outer hair cell stereociliary bundle, appears to be one of the early pathological features of surgically induced endolymphatic hydrops, which might be responsible for permanent sensorineural hearing loss. PMID- 8507470 TI - Pulsed versus continuous wave excitation mechanisms in photodynamic therapy of differently graded squamous cell carcinomas in tumor-implanted nude mice. AB - The effectiveness of photodynamic therapy (PDT) in vivo was compared between the pulsed excimer laser-pumped dye laser system (EDL) and the continuous wave (cw) argon laser-pumped dye laser system (ADL). Serial subcutaneous transplantation was used to implant thymus aplastic nude mice with different grades of malignancy of two human squamous cell carcinomas (SCCs). Forty-eight hours after i.v. injections of a hematoporphyrin derivative (Photosan 3), the animals were irradiated with either pulsed-EDL or cw-ADL laser light at a tumor depth of 4-5 mm. The irradiation data were chosen as follows: EDL and ADL wavelength 630 nm, total dose 150 J/cm2, irradiation time 27.78 min; EDL repetition rate 30 Hz, single pulse energy 3 mJ, pulse width 20 ns; ADL intensity 90 mW/cm2. The effects of PDT were studied either by long-term observation of the animals treated or by evaluation of hematoxylin-eosin and Ki-67 histological sections of tumors 48 h after treatment. The EDL system proved to be at least as efficient as the ADL system as judged by the number of complete remissions. This became particularly evident in the treatment of the lower-graded tumors, with a good response observed in both transplanted SCCs. However, the higher-graded tumors showed a better response to PDT. PMID- 8507471 TI - Glycerol effect on the guinea pig tectorial membrane. AB - The tectorial membrane (Tm) of guinea pigs has been found to have an altered organization of its matrix fibers in response to intravenously administered glycerol. Following treatment, the Tm middle zone shows an increase in waviness and clumping of fibers in non-hydropic and several hydropic ears in contrast to non-treated control ears. Residue of the internal sulcus cells occasionally fills the subtectorial space. In the present study, additional investigations were performed with scanning electron microscopy in order to study the relationship between the Tm and the organ of Corti, as well as the relationship between Hensen's stripe and the inner hair cell. Present findings provide evidence for a connection between the inner hair cell stereocilia and Hensen's stripe which may be the molecular basis for the modulation of hearing during the glycerol test in a patient with Meniere's disease. PMID- 8507472 TI - Structural changes in the middle ear tissues of the rat after fractionated irradiation. AB - Chronic suppurative otitis media often ensues in patients treated with irradiation against a head and neck tumor. In an experimental study, rats were exposed to irradiation to evaluate the sensitivity of the middle ear to an accumulated irradiation dose of 20-45 Gy. Observed otomicroscopically, all animals appeared to have normal tympanic membranes and no fluid developed in the middle ear space. Ten days after the irradiation, minor structural changes had occurred in the pars flaccida. The keratinizing epithelium had thickened and mitoses were seen histologically. The lamina propria was edematous and contained polymorphonuclear cells and macrophages. The middle ear mucosa from all other tissue sites appeared normal. Six months after irradiation only minor changes in the pars flaccida were evident: the lamina propria was thin and inelastic and macrophages were present in the stroma. It is inferred from this study that the middle ear of the rat is relatively resistant to irradiation. PMID- 8507473 TI - Degeneration of human respiratory cell ciliary beat in monolayer cell cultures. AB - The degeneration of ciliary beat of human respiratory cells was studied in monolayer cell cultures by using a differential interference microscope equipped with a high speed video system. This method for studying ciliary beat in cell cultures on collagen-coated cover glasses is quite advantageous, because it allows for detailed study of all parts of ciliary function and not just ciliary beat frequency (CBF). In the present study both CBF and ciliary beat amplitude (CBA) were found to decrease continuously from the 1st day after plating but the wave form of ciliary beat did not change. Cultures with high cell density provided better preservation of normal ciliary beat for a longer period. In contrast, ciliary beat degenerated quickly in cultures with low cell density. CBF and CBA in cell cultures less than 5 days after plating were always high, supporting use of these cultures for studies of normal ciliary motility. PMID- 8507474 TI - Differences in regulation of testis specifc lactate dehydrogenase in rat and mouse occur at multiple levels. AB - The testis specific form of lactate dehydrogenase (LDH-C4) is encoded by a single locus, Ldh-c, and is tightly regulated in a tissue specific manner. Here we show differences in expression of Ldh-c between rat and mouse, and describe the levels at which regulation of this gene differs in the two species. Our results demonstrate that the Ldh-c message level is nearly nine fold greater in mouse testis and remains high post-meiotically. In contrast, rat Ldh-c mRNA is highest in primary spermatocytes and reduced in spermatids. The results of nuclear run-on assays indicate that the transcription rate of Ldh-c is only moderately higher in mouse than rat, and cannot account for a significant portion of the observed differences. Similar decay rates for both rat and mouse Ldh-c mRNA in actinomycin D clearance assays indicate comparable cytoplasmic stabilities for the two messages. From these results we infer that nuclear prostranscriptional events contribute to the differences in Ldh-c message levels. PMID- 8507475 TI - Members of the raf gene family exhibit segment-specific patterns of expression in mouse epididymis. AB - The proto-oncogene c-raf-1 and the related genes A-raf and B-raf encode serine/threonine protein kinases thought to be involved in regulating gene expression by acting as part of second-messenger signaling pathways within the cell. Among the tissues in which A-raf and c-raf-1 have been shown to be expressed was mouse epididymis. The present studies were undertaken to determine if the raf family genes exhibited specificity in their pattern of expression that might be indicative of specific function in the epididymis. Northern and in situ hybridization analyses demonstrated that c-raf-1 mRNA was expressed as a 3.1 kb transcript at uniform levels throughout the length of the epididymis in all types of epididymal epithelial cells. Neither the germ cell-specific testicular transcripts nor the somatic transcripts of B-raf were detected by either Northern or in situ hybridization analysis in any region of the epididymis. A-raf, expressed as two transcripts of 2.6 and 4.3 kb, was the only gene examined which exhibited a segment-specific pattern of expression, being highest in the principal epithelial cells of the proximal caput epididymis and decreasing progressively in more distal regions of the tubule. These studies indicate that each raf gene exhibits a characteristic pattern of expression in the epididymis; A-raf in particular may play a unique regulatory role in the regionalized functions of the epididymis. PMID- 8507476 TI - Effect of sodium and betaine in culture media on development and relative rates of protein synthesis in preimplantation mouse embryos in vitro. AB - Results of recent experiments indicate that the improved development of mouse embryos in medium containing a low NaCl concentration (85 mM) or the inclusion of the organic osmolyte betaine in a medium containing a high NaCl concentration (125 mM) is correlated with the maintenance of intracellular sodium concentrations that more closely approximate those found in freshly isolated embryos (Biggers et al., 1993, Mol Reprod Dev 34:380-390). We examined the effect of these different culture media on the relative rates of protein synthesis since increased levels of intracellular sodium inhibit protein synthesis; a reduced rate of protein synthesis could therefore account for the differences in development in the different media, since cell division requires protein synthesis. We observe that the ability of these media to support development and to maintain more physiological concentrations of intracellular sodium is correlated with their ability to support increased relative rates of protein synthesis. Reducing the NaCl concentration from 125 mM to 85 mM leads to a greater fraction of the embryos developing from the 2-cell stage to the 8-cell stage after 1 day of culture and a substantially improves extent of development to the morula stage after 2 days of culture. This reduction in NaCl concentration also leads to a 2.4-fold increase in the relative rate of protein synthesis in 4 cell embryos. Moreover, addition of betaine to medium containing 125 mM NaCl increases the relative rate of protein synthesis. This finding provides an explanation, at least in part, for the increase in development to the blastocyst stage exhibited by mouse embryos cultured in these media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507477 TI - Nuclear transfer in cattle: effect of nuclear donor cells, cytoplast age, co culture, and embryo transfer. AB - There are many factors affecting the efficiency of nuclear transfer technology. Some are evaluated here using our novel approach by enucleating oocytes at 20-22 hr after in vitro maturation (IVM), culturing the enucleated oocytes (cytoplasts) for 8-10 hr or 18-20 hr to gain activation competence and then conducting nuclear transfer. In the first experiment, we demonstrated that cumulus cell (CC) monolayer can support some cloned embryos to develop into morulae or blastocysts. Co-culture with CC and bovine oviduct epithelial cell (BOEC) monolayers resulted in no differences (P > 0.05) in supporting the development of cloned embryos (Experiment 2). When in vitro matured oocytes were enucleated at 22 hr after IVM followed by nuclear transfer 18-20 hr later, cleavage and morula or blastocyst development of the cloned embryos were similar to those resulting from the enucleated oocytes which had been matured in vivo (Experiment 3). Frozen embryos as nuclear donor cells worked equally well as fresh embryos for cloning in embryo development which was superior to IVF embryos (Experiment 4). However, fresh embryos resulted in a higher proportion (P < 0.05) of blastomere recovery than did frozen of IVF embryos. Finally, embryo transfer of cloned embryos from our procedure produced a viable calf, demonstrating the commercial value of this novel approach of the technology. PMID- 8507478 TI - Isolation and biochemical characterization of heparin-binding proteins from boar seminal plasma: a dual role for spermadhesins in fertilization. AB - Sperm surface-coated heparin-binding proteins originating from secretions of the male sexual accessory glands, are known to play a pivotal role as extrinsic regulatory factors during sperm capacitation in many mammalian species. They interact with glycosaminoglycans present in the female genital tract and enhance the subsequent zona pellucida-induced acrosome reaction. We have isolated heparin binding proteins from boar seminal plasma by affinity chromatography on heparin Sepharose and reverse-phase HPLC. N-Terminal sequence analysis of these proteins identified a boar counterpart of the bovine capacitation factors BSP-A1/2 (also called PDC-109) and BSP-A3. Several carbohydrate- and zona pellucida-binding proteins, which belong to the newly described spermadhesin family, were also identified as heparin-binding proteins. Our results imply that, besides other capacitation factors, members of the spermadhesin family may play a dual role in sperm capacitation and fertilization in the pig. PMID- 8507479 TI - Vitelline coat of Unio elongatulus egg: I. Isolation and biochemical characterization. AB - In this study we isolated and purified the vitelline coat (vc) of Unio elongatulus eggs in order to investigate its protein and carbohydrate composition. SDS dissolved up to 80% of the vitelline coat protein content whereas 100 mM Ammonimum acetate (AA) at pH 11 and 1 mM lithium diiodosalicylate (LISH) dissolved only 40-50%. The ability of extremes of pH or LIS to solubilize the vitelline coats on eggs was then investigated. The results showed that pH from 7 to 11 progressively dissolved the vitelline coats without gross damage to the oocytes. SDS-PAGE of the solubilized material revealed only two components corresponding to the main components revealed by SDS-PAGE of the isolated vcs. These peptides have an apparent MW of 220 and 180 kD, are ConA positive, and seem to be connected to each other to form polycomponents. The latter feature is suggested by the electrophoretic pattern of the solubilized material under nondenaturing conditions. PMID- 8507480 TI - Inositol tri-phosphate inhuman and ascidian spermatozoa. AB - Using a specific protein binding assay we have shown that a spermatozoon of the ascidian Ciona intestinalis contains 1.58 +/- 0.74 x 10(-19) moles of inositol 1,4,5-tri-phosphate (InsP3), while a human spermatozoon contains 6.4 +/- 0.14 x 10(-19) moles. Induction of the acrosome reaction (AR) in both species, by exposure to the calcium ionophore A23187, does not significantly alter levels of InsP3, suggesting that phosphatidylinositol (PI) turnover is not necessary for the calcium ionophore induced AR. Furthermore, PI turnover in ascidian spermatozoa appears to be insensitive to lithium and phorbol ester. The high intracellular concentration of InsP3 in spermatozoa, corresponding to 50-200 microM, suggests it may play a role in egg activation. PMID- 8507481 TI - The specificity of human spermatozoa/zona pellucida interaction under hemizona assay conditions. AB - The objective of this prospective study was to evaluate the specificity of human sperm/zona pellucida interaction under hemizona assay (HZA) conditions in experiments with gametes from the same and different species. Human, cynomolgus monkey and hamster oocytes were used after salt-storage. Oocytes were bisected into matching hemizonae by micromanipulation and used in the HZA. Semen was obtained from healthy men (donors) and male cynomolgus monkeys and prepared by wash and swim-up. Sperm binding to matching hemizonae was assessed (tight binding) after 4-h coincubation in the HZA in homologous and interspecies experiments. Acrosome reaction was evaluated in the sperm droplets using FITC-PSA and on the hemizonae using the T-6 monoclonal antibody. On human hemizonae, the number of tightly bound sperm for human and monkey were 93.2 +/- 15.8 and 3.9 +/- 1.3, respectively (P < 0.001). On monkey hemizonae, the number of tightly bound sperm for monkey and human were 126.0 +/- 34.8 and 2.8 +/- 1.6, (P = 0.02) respectively. On hamster hemizonae, there was negligible binding of human and monkey sperm. There was a significantly higher incidence of acrosome reacted sperm on the zona pellucida in homologous compared to heterologous experiments. These results demonstrate a high species-specificity of human gamete functions under HZA conditions, providing further support for the use of this bioassay in infertility and contraception testing. PMID- 8507482 TI - Capacity of rete testicular and cauda epididymal boar spermatozoa to undergo the acrosome reaction and subsequent fusion with egg plasma membrane. AB - The capacity to undergo the acrosome reaction and subsequent fusion with egg plasma membrane was examined in rete testicular and cauda epididymal spermatozoa from boars. Sperm penetration assay using zona-free hamster eggs demonstrated that the penetration rates for rete testicular spermatozoa preincubated for induction of the acrosome reaction for 2 and 3 h were 55% and 97%, respectively. However, most of the eggs (93%) were penetrated with polyspermy by cauda epididymal cells preincubated for 2 h. Results obtained by the triple-stain technique revealed the percentages of acrosome-reacted spermatozoa in the rete testicular and cauda epididymal samples preincubated for 3 h to be 61% and 74%, respectively. These results indicate that many rete testicular spermatozoa possess the capacity to undergo the acrosome reaction and subsequent fusion with egg plasma membrane in vitro, which appears to be completely established only after sperm transit through at least the proximal part of the epididymis. PMID- 8507483 TI - Local alteration of cortical actin in Xenopus eggs by the fertilizing sperm. AB - Rhodamine phalloidin (Rph) staining was used to examine the microfilament organization of the Xenopus laevis egg cortex during the early stages of fertilization. Unactivated eggs possessed a cytochalasin B (CB)-insensitive Rph stained matrix that was reorganized upon egg activation and diminished in the presence of CB. Xenopus laevis sperm caused a temporary local increase in Rph staining on the Xenopus cortex. In CB-treated eggs, the local increases of cortical Rph staining later changed to a Rph-free area. These temporary local increases of cortical Rph staining were also observed when Notophthalmus viridescens sperm fertilized Xenopus and Rana pipiens eggs, and were followed by the appearance of concentric rings of stained and unstained areas. Our data suggest that Xenopus and Notophthalmus sperm have activities that can both organize and disrupt the cortical filamentous actin of the Xenopus egg. PMID- 8507484 TI - Role of glutathione in the maturation and fertilization of pig oocytes in vitro. AB - The present study examined, by treatment of buthionine sulfoximine (BSO), which is a specific inhibitor of glutathione (GSH) synthesis, the role of GSH in the maturation and fertilization of pig oocytes in vitro. Follicular oocytes collected from prepubertal gilts at a local slaughterhouse were cultured for 36 h in Waymouth MB 752/1 with or without BSO (1 mM), fertilized in vitro, and assessed for GSH concentration (before insemination), maturation, and fertilization. The addition of BSO to maturation medium immediately after culture (Group I), 12 h after culture (Group II), or 24 h after culture (Group III) significantly decreased the GSH concentration in pig oocytes compared with the control (P < 0.01), whereas the rate of cumulus mass expansion at 36 h of culture and the rates of nuclear maturation and sperm penetration following in vitro insemination did not differ. However, the rate of pig oocytes having condensed sperm heads was significantly lower and the rate of male pronucleus formation of pig oocytes was significantly higher in oocytes matured in the control and Group III than in oocytes matured in Groups I and II (P < 0.01). In experiment 2, when BSO was added to maturation media 15, 18, 21, or 24 h after culture, the rate of pig oocytes having condensed sperm heads was significantly lower and the rate of male pronucleus formation of pig oocytes was significantly higher in oocytes matured in the medium supplemented with BSO at 21 or 24 h of culture than in oocytes matured in other groups (P < 0.05 or P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507485 TI - Expression of proto-oncogenes in mouse eggs and preimplantation embryos. AB - The expression of several protooncogenes has been investigated in mouse eggs and preimplantation embryos using reverse transcription coupled to amplification of cDNAs by the polymerase chain reaction (RT-PCR). The genes chosen for analysis included both cytoplasmic (c-raf-1, rasH, rasK, and rasN) and nuclear (c-fos and c-myc) proto-oncogenes encoding proteins involved in the transduction of signals from protein-tyrosine kinase growth factor receptors. Transcripts of the cytoplasmic proto-oncogenes were detected both as maternal and embryonic mRNAs at levels (ca. 1,000 copies per egg or embryo) approximately comparable to their levels of transcription in somatic cells. Transcripts of c-fos and c-myc were also detected in both eggs and embryos, although at more variable levels: Maternal transcripts were present at very low levels (ca. 1-10 copies per egg) in growing oocytes and ovulated eggs; embryonic transcription of c-myc increased, reaching mRNA levels of approximately 100-1,000 copies per embryo in four-cell embryos, morula, and blastocysts; in contrast the transcription of c-fos remained at low, barely detectable levels throughout preimplantation development. Although the significance of the low levels of c-fos mRNA is unclear, these results indicate that preimplantation embryos possess the basic intracellular signaling apparatus required to respond to polypeptide growth factors. PMID- 8507487 TI - Cell multiplication. PMID- 8507486 TI - Zona-free sperm penetration assay and inducers of the acrosome reaction: a model for sperm microinjection under the zona pellucida. AB - In order to minimize the percentage of false-negative results in the zona-free sperm penetration assay (SPA), a wide range of substances and/or physical agents capable of inducing the acrosome reaction (AR) have been incorporated in the incubation medium. These agents can also be used for treatment of severe male infertility using the technique of sperm microinjection under the zona pellucida (SMUZ). In the present review, the percentages of acrosome-reacted spermatozoa induced by several physiological, biochemical or physical agents published in the literature are compared in order to find the most efficient method(s) of inducing the AR in human sperm as a previous requirement of optimizing the technique of SMUZ. A working estimate of the level of efficiency of a given AR inducer is calculated by adding up its range score in each of three different arrangements from the highest to the lowest value of percentages of AR and differences in percentages of AR and penetration indexes between treated and control groups in SPA. The agents able to induce the AR by nonphysiological (electropermeabilization, lysophosphatidyl choline, and freezing-thawing) have better positions in this hierarchical system than those ones which require the active participation of sperm membrane receptors or second messenger systems (progesterone, zona pellucida, and stimulators of protein kinase A). Electropermeabilization appears to be the most efficient AR inducer. However, more possibilities need to be explored to enhance the relatively low percentages of acrosome-reacted spermatozoa shown by infertile men. PMID- 8507488 TI - Control of the yeast cell cycle by the Cdc28 protein kinase. AB - It is becoming increasingly apparent that the diverse functions of Cdc28 during the yeast cell cycle are performed by forms of the kinase that are distinguished by their cyclin subunits. Entry into the cell cycle at START involves the Cln cyclins. S phase needs Clb5 or Clb6 B-type cyclins. Bipolar mitotic spindle formation involves Clb1-4 B-type cyclins. Much of the order and timing of the cell cycle events may involve the progressive activation of Cdc28 kinase activities associated with different cyclins, whose periodicity during the cycle is determined by both transcriptional and post-transcriptional controls. PMID- 8507489 TI - Activation of the various cyclin/cdc2 protein kinases. AB - Recent research has led to the near culmination of the biochemical confirmation of the most basic genetic predictions about how p34cdc2 activity is controlled. The field is now moving from a biochemical dissection of the machinery to understanding how the system is regulated. The discovery of numerous, highly related protein kinase complexes that control other cell cycle events will test the generality of this paradigm. PMID- 8507490 TI - Targets of cyclin-dependent protein kinases. AB - Our current understanding of the eukaryotic cell cycle attributes a key regulatory role to cyclin-dependent protein kinases. It is important, therefore, to identify the physiological substrates of these kinases, and to understand how the phosphorylation of such proteins promotes cell cycle progression. PMID- 8507491 TI - Integration of cell cycle control with transcriptional regulation by the retinoblastoma protein. AB - Rapid progress in several areas of molecular biology has led to the realization that the retinoblastoma protein may play a pivotal role in the coordination between cell cycle control and regulation of gene expression. This role is a subtle one, and is important in only certain mammalian cell types. Exploring the details of these connections, and why only some cells rely on them, is already beginning to shed light on the regulation of cell multiplication. PMID- 8507492 TI - Turning DNA replication on and off. AB - DNA replication is coupled to cell cycle progression at a major regulatory point in the G1 phase of the cell cycle. At this point, the catalytic subunit of a protein kinase (encoded by the CDC28 gene in budding yeast or the homologous CDC2 gene in other eukaryotes) is activated by binding to a positively acting regulatory subunit, a cyclin. Recent research has revealed evidence for two pathways that might connect these kinases to the proteins that replicate DNA: activation of an essential replication factor, or removal of the block that limits genome duplication to once per cell cycle. PMID- 8507493 TI - Doing the right thing: feedback control and p53. AB - Recent evidence suggests that exposure of cells to DNA-damaging agents causes a rise in the levels of the p53 tumor suppressor protein and arrest of progression through the cell cycle. p53 may therefore resemble a member of the RAD gene class identified in yeast, RAD9, which allows cells to repair DNA before continuation of the cell cycle. The evidence that p53 is a sequence-specific, DNA-binding protein that can regulate transcription suggests several ways in which p53 might effect this growth cessation. PMID- 8507494 TI - Cell division in plants. AB - The past couple of years have seen the isolation and characterization of many of the regulatory genes from plants that are thought to be intimately involved in regulation of the cell division cycle. In addition, characterization of plant specific aspects of the cell division cycle has provided insight into how spatial and temporal controls may be linked. The comparative lack of cell mobility means that plant organs are historic records of the cell cycles that occurred during their evolution. Differentiated cells retain a capacity for re-entry into the cell cycle, which is probably an adaptation to compensate for the damage that they must tolerate because of a sedentary lifestyle. Understanding how plants cope with such damage and manage to generate such an array of diverse multicellular structures will require a basic comprehension of cell division. PMID- 8507495 TI - Chromosome segregation and cytokinesis in bacteria. AB - Substantial progress has recently been made in the understanding of chromosome partitioning and cytokinesis in bacteria. The biochemical properties of some key protein components involved in these processes are beginning to emerge. New evidence supports the recently developed notion that, in prokaryotic cells, basic cell biological processes rely on the activity of previously unidentified cytoskeletal-like elements. PMID- 8507496 TI - Protein kinases with calmodulin-like domains: novel targets of calcium signals in plants. AB - Recently, a novel calcium-dependent protein kinase has been identified that is structurally distinguished by the localization of a calcium-binding regulatory domain fused to a serine/threonine catalytic domain. The regulatory domain is homologous to calmodulin and contains four helix-loop-helix calcium-binding sites. As a result, the kinase is directly activated by calcium without a requirement for other effector molecules. PMID- 8507497 TI - The multifunctional Ca2+/calmodulin-dependent protein kinases. AB - Ca2+ mediates the effect of many hormones, neurotransmitters and growth factors on contractility and motility, carbohydrate metabolism, cell cycle, gene expression and neuronal plasticity. Multifunctional Ca2+/calmodulin-dependent (CaM) kinase, CaM kinase Ia, CaM kinase Ib and CaM kinase IV are four of the kinases that mediate Ca(2+)-signaling pathways. Recent studies have clarified our understanding of their structure, regulation and function. PMID- 8507498 TI - EGF: new tricks for an old growth factor. AB - During the past year, the biology of epidermal growth factor (EGF) has been investigated in lower organisms (Caenorhabditis elegans, Drosophila and bacteria). These experiments have produced some surprising results: the identification of defects produced by mutation of EGF-like genes; the role of EGF receptors in bacterial invasion; and the role of EGF-like precursors as receptors for a bacteria toxin. PMID- 8507499 TI - The regulatory diversity of the mammalian adenylyl cyclases. AB - Clones for six mammalian adenylyl cyclases have recently been isolated. One of these enzymes, the type I calmodulin-sensitive adenylyl cyclase, is neurospecific and is implicated in neuroplasticity. We propose that the type I adenylyl cyclase may be important for learning and memory because it allows Ca(2+)-amplified cAMP signals, synergism between Ca2+ and cAMP-activated kinases, and positive feedback regulation of Ca2+ channels by cAMP-dependent protein kinase. PMID- 8507500 TI - Apoptosis and signal transduction: clues to a molecular mechanism. AB - Apoptosis, or programmed cell death, plays an essential role in specific cell deletion during normal embryonic and adult development in vertebrate and invertebrate species. Recent evidence suggests that signal transduction pathways governing cellular proliferation and cell cycle progression also mediate the physiological response to changes in the extracellular environment that trigger the anti-proliferative state characteristic of apoptosis. PMID- 8507501 TI - Cell multiplication. PMID- 8507502 TI - American Society of Echocardiography. 4th Annual Scientific Sessions. Orlando, Florida, June 16-18, 1993. PMID- 8507503 TI - [Specificity of the dystrophin immunohistochemical technique in muscular dystrophy]. AB - We have used a monoclonal antibody against the portion of the dystrophin molecule known as a mid rod using an immunoperoxidase technique in 41 muscle biopsies of patients with different muscle diseases. Twelve of the patients suffered a Xp21 dystrophy, nine of them had the Duchenne type and three the Becker. All the patients affected by a non Xp21 dystrophy had a normal dystrophin labelling pattern in their muscle fibres. The labelling patterns in the Duchenne biopsies were of three types. In seven of them we found no dystrophin at all. One showed only small nuclei of fibres with a normal amount of dystrophin in them. The last patient showed a weak labelling pattern in the majority of his fibres. In the two Becker dystrophy-type biopsies the expression of dystrophin varied. In one of them we could see a clear labelling pattern in all fibres, while the other showed a disruptive pattern with some portions of the sarcolemic membrane without dystrophin. We concluded the report enhancing the enormous support that this technique means particularly in the biopsies of patients suffering from an Xp21 alterations. PMID- 8507504 TI - The molecular genetics of neurological disease. Recent advances. PMID- 8507505 TI - [Localization of E(wa) in Drosophila melanogaster using rearrangement]. AB - The white-apricot (wa) allele differs from the wild type white gene by the presence of the retrovirus-like transposable element copia within the transcription unit. The activity of wa is reduced in trans by a semidominant mutation in the gene Enhancer-of white-apricot (E(wa)). The map position of E(wa) is refined by analyzing recombination among three genes: px, E(wa) and sp. The recombinational distance between E(wa) and sp is 0.2 cM, which places E(wa) at 2 106.8. To localize E(wa) cytologically, four Y; 2 translocations, one 1;2 translocation and three 2R deficiency stocks were crossed to the suitable E(wa) stocks and the wa sons were scored for intensity of pigment and the speck at the axis of wings. The E(wa) was placed in the distal portion of 60B. The one E(wa) mutation and two sp mutations derived from our gamma-ray mutagenesis were used for examination of polytene chromosome. The former was a revertant which has a cytologically visible insertion of material from an unknown source at 60B5-13, most likely in the 60B8-9. It is likely that this insertion is within the E(wa) gene. The latter shows breakpoint at 60C1-2, where is likely the location of the sp gene. Combining the data of both cytological localization and recombinational mapping, the E(wa) was localized at 60B5-13, most likely in the 60B8-9, the left of sp but very close to it. PMID- 8507506 TI - [Molecular and clinical cytogenetic studies of a family with a 22p+ marker chromosome]. AB - A male with gonadal dysgenesis and a 22p+ was observed. Molecular and Clinical Cytogenetic studies have been carried out on the members of the family. The results showed that there was a 22p+ marker chromosome transmitted from the maternal grandmother of the proband to 6 members of this family. Its short arm showed a homogeneously dull stained region in C-banded preparations and a narrow dark or light stained band in R-, G-banded preparations respectively. A large Ag band or double NORs was also observed on p+. The chromosomal in situ hybridization with tritium labelled rRNA gene probe demonstrated that the distribution of the silver grains was along the entire p+ of the marker chromosome. The number of silver grains on the short arm of the p+ was 3.9 times as that of any other normal acrocentric chromosomes. Two cases of female with repeated spontaneous abortions and 2 cases of male with gonadal dysgenesis were found by family study. Our studies, combining with previous literatures suggested that these abnormalities were probably in association with p+ marker chromosome. PMID- 8507507 TI - Light transmission in bonded ceramic restorations. PMID- 8507508 TI - Esthetics and anterior tooth position: an orthodontic perspective. Part I: Crown length. PMID- 8507509 TI - Esthetic principles for full crown restorations. Part I: Tooth preparation. PMID- 8507510 TI - Esthetic high-strength implant abutments. Part I. PMID- 8507511 TI - Factors in dentin bonding. Part 1: A review of the morphology and physiology of human dentin. AB - Dentin bonding has been the object of intensive research for many years. If a substance is expected to bond to a natural tooth surface, the morphologic and physiologic characteristics of the substrate determine both the bonding applications and testing methods used. PMID- 8507512 TI - [Nursing managers need their own trade union. Interview by Kjell Arne Bakke]. PMID- 8507513 TI - [Rehabilitation center becomes hospital. Interview by Erik Larsen]. PMID- 8507514 TI - [With a mandate to help. Interview by Siv Barstad]. PMID- 8507515 TI - [Danger of nurses' strike in Denmark]. PMID- 8507516 TI - [Nursing under a different sky: Tartagal]. PMID- 8507517 TI - [Poverty kills motivation]. PMID- 8507518 TI - [Norwegian nurse recruits members in Zambia. Interview by Kjell Arne Bakke]. PMID- 8507519 TI - [Student wages in psychiatry]. PMID- 8507520 TI - [Child welfare--dependent on you. Take responsibility in time. Interview by Marit Fonn]. PMID- 8507521 TI - [Ear thermometer shows incorrect temperature]. PMID- 8507522 TI - [Ear thermometer shows incorrect temperature. Can have dramatic consequences. Interview by Kjell Arne Bakke]. PMID- 8507524 TI - [Urine testing in suspicion of drug abuse]. PMID- 8507523 TI - [We feel ourselves as if we are on display]. PMID- 8507525 TI - [Maternity-child center on West Bank]. PMID- 8507526 TI - [Nursing under a different sky: Lebanon]. PMID- 8507527 TI - [Infection at the wheel]. PMID- 8507528 TI - [Child welfare--dependent on you. "I am worried for the children's sake". Interview by Marit Fonn]. PMID- 8507529 TI - [Child welfare--dependent on you. From duty to silence to obligation to report. Interview by Marit Fonn]. PMID- 8507530 TI - [Child welfare--dependent on you. Alternative child welfare. Interview by Marit Fonn]. PMID- 8507531 TI - Worthwhile efforts for skin cancer prevention. PMID- 8507532 TI - Dermatologic disease does the talk show circuit. PMID- 8507533 TI - Tattoos on women: marks of distinction or abomination? AB - Professional and amateur tattooing on women is flourishing. Understanding the tattooing procedure, the rationale for obtaining a tattoo, and the associated risks are important to better understand clients' needs and to develop health education. Nursing care for women requesting removal of their tattoos with laser therapy is presented. PMID- 8507534 TI - Clinical camouflage: a burn survivor's case study. AB - A clinical methodology involving consultation, assessment, plan, implementation, and evaluation is important in meeting patients' skin care and cosmetic needs. Part One of this three-part series examines how this systematic and practical approach was used in treating a burn patient. PMID- 8507535 TI - What's your assessment? Herpes zoster. PMID- 8507536 TI - The technique of patch testing: role of the office staff. AB - Patch testing is a very useful office diagnostic tool to help clarify the cause of allergic contact dermatitis. The dermatology nursing staff can help the physician with some of the time-consuming steps in using this technique, which can be very valuable to patient outcome. PMID- 8507537 TI - Management of a vitiligo patient: a case study. AB - Vitiligo is a chronic cutaneous disorder characterized by irregular patches of pigment loss. PUVA treatment for vitiligo and its accompanying nursing care considerations are discussed in this case study. PMID- 8507538 TI - Dermatology Nurses' Association position statement on prevention and early detection of skin cancer. PMID- 8507539 TI - Interleukin-2-administration intravenously and intrapleurally in a patient with primary pulmonary adenocarcinoma. Cellular responses in peripheral blood, intrapleural fluid and bronchoalveolar lavage. AB - A case report of a patient who suffered from a rapidly progressive lung adenocarcinoma with malignant pleural effusions, is given. The patient failed to respond on two series of conventional cytotoxic drug therapy (Carboplatin, Etoposide). Interleukin-2 (IL-2) treatment was first started as intrapleural instillations (3.0 million IU per day in 6 days). A clear clinical response was achieved with ceasing of the pleural effusion, and the overall disease became stable. In the peripheral blood, there was an increase of CD4 positive lymphocytes that remained elevated after finishing the installation period. Both in bronchoalveolar lavage (BAL), and in the pleural fluid, there was a marked decrease of cells recovered, possibly due to an enhanced tissue attachment of activated cells. A second analysis with subtyping of lymphocytes in BAL was impossible due to the low cell number. In the pleural fluid, the fractions of CD3 positive cells increased from 20 to 71% while the ratio between CD4 and CD8 remained persistently elevated at 6.1:1. Because of the disappearance of the pleural effusion, the patient was thereafter treated with IL-2 given as a continuous infusion (18 million IU per square-metre during 24 hours for 5 days). Hereby a more pronounced cell response was achieved in the peripheral blood. In contrast to the intrapleural treatment route, not only CD4 positive cells, but also the numbers of natural killer cells (NK) increased. However this treatment was also associated with a much higher degree of side effects. It can be concluded from both intrapleural and intravenous IL-2 therapy, that a clinical and immunological response was achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507540 TI - Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study. AB - The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group. The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p = 0.074; generalized Kruskal-Wallis, p = 0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Kruskal-Wallis, p = 0.045). No side effects attributable to SPG were recorded. The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients. PMID- 8507541 TI - Clinical usefulness of continuous administration of Nocardia rubra cell wall skeleton (N-CWS) in diffuse panbronchiolitis (DPB). AB - Eight patients with diffuse panbronchiolitis (DPB) who had repeated intractable airway infections were continuously treated with Nocardia rubra cell wall skeleton (N-CWS), a biological response modifier. As a result, subjective symptoms were reduced in 6 patients. Antibiotics therapy could be discontinued completely in two patients and the dose of antibiotics could be reduced considerably in two other patients. No adverse reactions in relation to N-CWS were observed. These results suggest that N-CWS is effective in treating erythromycin-resistant DPB. PMID- 8507542 TI - Autologous tumour-specific cytotoxic T-cell clone established from tumour infiltrating lymphocytes (TIL) of malignant ascites in the absence of recombinant interleukin 2(rIL2): activation by autologous tumour cell alone. AB - Mixtures of tumour infiltrating lymphocytes (TIL) and tumour cells collected from malignant ascites of a patient with pancreatic cancer were cultured using a microplate without recombinant interleukin 2(rIL2). TIL rapidly proliferated from 21-51 days after the initiation of culture in 20 out of 30 wells tested. Cytotoxicity was examined in 5 out of the 20 TIL-growing wells. One CD8+ TIL (well-1) displayed autologous tumour-specific cytotoxicity. Repeated stimulation with autologous tumour cells, in the absence of rIL2, was required for further propagation in long-term (60 days) culture of TIL. Four clones were established from well-1 by limiting dilution without rIL2. Surface phenotypes of the 4 clones were the same as those of well-1, i.e., CD8+, CD16-, CD25+, HLA-DR+. And autologous tumour cells were required for continuous proliferation of these CD8+ T-cell clones. Both well-1 and the 4 clones displayed similar degrees of cytotoxicity restricted to autologous tumour cells. These results indicate that TIL from malignant ascites may contain precursor cytotoxic T-lymphocytes (CTL) sensitized in vivo to autologous tumour cells, and that TIL are able to grow for several weeks or more with substantial increases in cell numbers in the absence of rIL2. PMID- 8507543 TI - The expression and biological activity of IL-2 receptor on a human pancreas cancer cell line. AB - To ascertain whether the tumor cells can regulate the host immune systems through the production of the cytokines or their receptors, we examined the expressions of tumor necrosis factor alpha (TNF alpha), tumor necrosis factor beta (TNF beta), interleukin 2 (IL-2) and interleukin 2 receptor alpha chain (IL-2R alpha) on the human cancer cell lines by Northern blot analysis. We used K562 (leukemia cell line), MCF-7 (breast cancer cell line), LS180, HT29 (colon cancer cell lines), SH101 (gastric cancer cell line) and PH101 (pancreas cancer cell line). Expressions of TNF alpha, TNF beta and IL-2 mRNA were not detected in any of the tumor cell lines. However, 1.4 and 3.5 kilobases of the IL-2R alpha mRNA were expressed in the PH101 cells, but not in the other five cell lines. Furthermore, IL-2R alpha was detected on the cell surface of the PH101 cells by the flow cytometric analysis with an anti-IL-2R alpha monoclonal antibody. Interestingly, the soluble IL-2R alpha (sIL-2R alpha) was found in the conditioned media obtained from the PH101 cell culture with a sandwich enzyme immunoassay. Moreover, the sIL-2R alpha secreted from the PH101 cells blocked the IL-2 dependent lymphocyte proliferation. These results indicate that the expression of IL-2R alpha on PH101 might suppress the IL-2 induced lymphocyte proliferation. PMID- 8507544 TI - The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from gastric or colorectal cancers. AB - Twenty-four patients with liver metastases from gastric or colorectal cancer were treated with OK-432-combined adoptive immunotherapy (AIT). Lymphocytes isolated from regional lymph nodes or peripheral blood were cultured with medium containing T cell growth factor and sonicated tumor extract antigen (SE-Ag) for 9 13 days. The cultured lymphocytes were transferred mainly through the hepatic artery after the administration of OK-432, a streptococcal preparation. Sixteen of the 24 patients received a low dose of anti-cancer agents between the OK-432 injection and cell transfer. When cultured without SE-Ag, regional lymph node lymphocytes (RLNL) showed significantly (P < 0.05) higher cytotoxic activity against autologous tumor cells and, on the contrary, lower cytotoxic activity against K562 than peripheral blood lymphocytes (PBL). When cultured with SE-Ag, cytotoxicity of RLNL against autologous tumor cells was nearly equivalent to that of PBL. The blastogenesis of fresh PBL to SE-Ag was significantly (P < 0.05) augmented after the OK-432-combined AIT. Two patients showed complete response and 4 patients showed partial response among 19 patients who had evaluable lesions. Five patients whose liver metastases were resected were treated with OK 432-combined AIT as an adjuvant therapy. To date they are alive without recurrence in the liver. PMID- 8507545 TI - Cellular interaction against autologous tumor cells between IL-2-cultured lymphocytes and fresh peripheral blood lymphocytes in patients with breast cancer given immuno-chemotherapy. AB - In patients with Stage II or III breast cancer and in patients with liver metastases from breast cancer, we examined cellular interaction in the cytotoxicity against autologous tumor cells by interleukin-2(IL-2)-cultured lymphocytes (CL) and fresh peripheral blood lymphocytes (FPBL) treated with immunochemotherapy including OK-432 and cyclophosphamide. In flow cytometric analysis, CD8+CD11b+ and CD16+ cells significantly decreased after immuno chemotherapy in both groups of patients. A protocol study in Stage II or III breast cancer patients showed suppressive activity of FPBL on the cytotoxic activity of CL in 3/9 of the non-treatment group but no suppressive activity and enhancing activity in 3/7 in the immuno-chemotherapy group. Moreover, in 19 patients with liver metastases from breast cancer treated with immuno chemotherapy including adoptive immunotherapy, FPBL in 6/19 showed enhancing activity, and in 8/19 suppressive activity in the lysis of autologous tumor cells. In assays in vitro using autologous and allogeneic tumor cells, FPBL showed a partial specificity in cellular interaction against autologous tumor cells. CD4-depleted FPBL inhibited cytotoxicity of CL, while CD8-depleted FPBL enhanced cytotoxicity of CL in patients with liver metastases. These results suggest that immuno-chemotherapy eliminates the suppressive population in FPBL and may induce tumor regression if combined with adoptive immunotherapy using CL. PMID- 8507546 TI - The lymphatic route. VIII. Distribution and plasma clearance of recombinant human interleukin-2 after SC administration with albumin in patients. AB - It has been postulated that favouring the absorption of interleukin-2 via lymphatics rather than venous capillaries after subcutaneous administration may improve its therapeutic index. We have now evaluated in 12 cancer patients the plasma pharmacokinetic of interleukin-2 either dissolved in water or in 20% albumin solution with an internal cross-over after at least three days. Our data show that when albumin is present, the plasma concentrations of interleukin-2 versus time is increased and swelling at the injection sites is reduced. It remains to be seen whether efficacy improves during a prolonged treatment. PMID- 8507547 TI - Dipole source analysis of rolandic spikes in benign rolandic epilepsy and other clinical syndromes. AB - Dipole source analysis of rolandic spike-and-wave complexes was performed in 48 children. The estimated source of the rolandic spike, of the trough between the spike and the following slow wave, and of the slow wave appeared to have the same position but had a small significant difference in orientation. Despite the heterogeneity of associated clinical syndromes, there were no clear differences between the clinical categories of patients regarding the localization and the orientation of the sources of the rolandic spike, trough and slow wave. The presence of a second source could explain the ascending phase of the rolandic spike in 19 children. This combination of two sources corresponded with the "double-spike phenomenon" that had been found previously by sequential brain mapping and which was associated with epilepsy. The preceding spike source and the source of the rolandic spike-and-wave complex were found to have the same position but a different orientation. A hypothetical explanation is proposed in which the presence of the rolandic spike-and-wave complex alone is insufficient to account for the clinical symptomatology. Both the preceding spike source and the source of the rolandic spike-and-wave complex, representing two separate, nearby but differently oriented populations of neurones in the inferior part of the rolandic cortex, is necessary for the development of epileptic manifestations. PMID- 8507548 TI - STL: a spatio-temporal characterization of focal interictal events. AB - An innovative method for on-line processing of array ECoG data, the Spatio Temporal Laplacian, intended for intraoperative epileptic focus localization is presented. This method simultaneously involves the spatial and temporal characteristics of the potential field manifestations peculiar to focal interictal events. A 3-Dimensional (x, y and t) sample space is used to explain and apply the Spatio-Temporal Laplacian (STL) transformation. In particular, a focal interictal event is detected through the coincident spatial and temporal sharpness that it introduces in this sample space. Preliminary results from two subjects are presented and compared with standard bioplar derivation signals, traditionally used in the focus localization task. PMID- 8507549 TI - Evidence for multiple generators in evoked responses using finite difference field mapping: auditory evoked fields. AB - Electric potential maps and magnetic field maps have been used to study brain electrical activity. During the temporal course of an evoked cortical response, the electrical activity of specific neuronal subpopulations change in a sequential manner giving rise to measurable electrical potentials and magnetic fields. For these potentials and fields, both the amplitude and rate of amplitude change have characteristic, time-dependent waveforms. Presently, amplitude waveforms from multiple locations are used to generate magnetic field and electric potential maps which have been found to be useful in understanding the activity of the neurons which give rise to these maps (Romani 1990). This paper introduces a data transformation technique which results in a derived map that we have termed a "finite difference field map" (FDFM). This mapping technique provides information associated with the rate at which the amplitude of the neuronal electric activity changes. In this paper, some advantage of FDFM analysis are illustrated by application of this technique to the study of the auditory evoked cortical field (AECF) N1m waveform. Using data obtained from normal subjects it will be demonstrated that application of the FDFM technique allows the localization of the primary N1m source at an earlier latency than is possible using the conventional waveform data. The source location determined at an early latency by FDFM analysis was identical to that obtained at later from the conventional field data. These data suggest that the primary N1m source is stationary. In addition, analysis of the time sequence of FDFM field maps contains evidence of a second spatially separate source which is co-active with primary N1m source. PMID- 8507550 TI - Alpha frequency, cognitive load and memory performance. AB - EEG-signals were recorded from subjects as they performed a modified version of Schneider's and Shiffrin's memory search paradigm. The hypothesis was tested whether individual (centre of gravity) alpha frequency, termed IAF, is related to memory performance and/or attentional demands. The results show that memory performance exerts the strongest effect on IAF. As compared to a resting period, the difference in IAF between age-matched good and bad memory performers reached a maximum when subjects were actually retrieving information from their memory. During retrieval, the IAF of good performers is 1.25 Hz higher than for bad performers. Attentional and task demands also tend to reduce IAF, but as compared to memory performance-to a much lesser degree. The results of amplitude analyses demonstrate further that during retrieval, alpha desynchronization is more pronounced for bad performers than for good performers. Taken together, the results indicate that a decrease in IAF is always related to a drop in performance. PMID- 8507551 TI - Scalp topography of somatosensory evoked potentials following median and posterior tibial nerve stimulation in Down's syndrome. AB - The scalp topography of somatosensory evoked potentials (SEPs) following stimulation of the median and posterior tibial nerve of 39 patients with Down's syndrome was compared with that of age-matched normal controls using significance probability mapping (SPM). The maximal area of each potential in Down's syndrome was similar to that in normal controls, but the scalp distribution was wider. The amplitudes of all components, except the N45 and P59 potentials of the posterior tibial nerve SEPs, were greater in Down's syndrome, and the t values calculated by SPM were significantly greater. However, the difference of SEP maps between Down's patients and aged controls (over 65 years) was much smaller than that between Down's patients and age-matched controls. Therefore, we conclude that the generator sources and generating mechanisms of SEPs in Down's syndrome are not different from those of normal control, however SEP potentials in Down's syndrome are remarkably enhanced, resulting in a wider distribution, probably due to accelerated aging in Down's patients. PMID- 8507552 TI - In vivo validation of distributed source solutions for the biomagnetic inverse problem. AB - Probabilistic modelling of continuous current sources is applied to the analysis of MEG signals generated by current dipoles implanted in the head of a living human subject. Estimates of the distribution of activity within a circular disk are obtained from signals generated by a single implanted dipole and by a pair of simultaneously active implanted dipoles. The orientation and depth of the disc is determined in advance from the experimental geometry and the measurements. The resulting reconstructions constitute the first in vivo validation of distributed source imaging; they provide a complementary test to earlier works using computer generated data and tests using point source analysis of signals generated by a single implanted dipole. In this work we provide a literal test of spatial resolution by resolving two nearby point-like sources. Temporal resolution is addressed in a de facto manner by imaging at one millisecond intervals. Computer simulations, with controlled amount of noise, are used to demonstrate the robustness of the results, and show the interplay between high spatial accuracy and noise insensitivity. PMID- 8507553 TI - Estimates of brain activity using magnetic field tomography in a GO/NOGO avoidance paradigm. AB - This paper presents the first estimates of three dimensional evolution of activity in the brain associated with a GO/NOGO avoidance (CNV) paradigm. These estimates are continuous probabilistic solutions (Ioannides et al. 1990) to the biomagnetic inverse problem, obtained from averaged multichannel magnetoencephalographic (MEG) recordings (Vieth et al. 1991). The emphasis here is placed on the comparison of the activity associated with the GO and NOGO conditions; estimates of activity are shown for the onset of warning stimulus (S1), the early response half a second after S1, the late response lasting for over one second before S2 (the time between S1 and S2 is 3.5 seconds) and the onset of the imperative stimulus (S2). We find responses in regions of the brain implicated with hearing the stimulus, task engagement and motor output. Differences in the images corresponding to GO and NOGO conditions are significant because they reflect differences in brain function when a motor response is required or must be inhibited. PMID- 8507554 TI - Brain mapping: a contribution to linear interpolation. AB - Topographic mapping of brain electrical activity has become a powerful tool in neurological diagnosis. Maps are obtained from a reduced number of actual measurements by means of mathematical interpolation. Most of these systems use linear combination of the values measured and, in spite of its importance, the choice of the exponent "n" in the weighting function is made ad hoc. In this paper we present a critical analysis of such method and propose an objective criterion for the estimation of that exponent. As well, we propose another criterion for determining the number of leads used in the interpolation of each point. PMID- 8507555 TI - Special issue dedicated to Professor G. Barry Pierce. PMID- 8507556 TI - Differential synthesis of type 1 and type 2 desmocollin mRNAs in human stratified epithelia. AB - Epithelial cells are tightly connected by various kinds of junctions, of which the desmosomes (maculae adhaerentes) are particularly prominent. The desmosomes are characterized by two subgroups of constitutive transmembrane glycoproteins, the desmogleins and the desmocollins, which have been identified as specific members of the larger multigene family of CAMs of the cadherin category. Following our recent observation in bovine tissues that different desmoglein and desmocollin genes can be expressed in different cell types (Koch, P.J. et al., Proc. Natl. Acad. Sci. USA 89:353-357, 1992), we have now isolated cDNAs encoding human desmocollins type 1 and type 2. The complete sequence of human type 1 desmocollin has been determined and identified by its homology to the corresponding bovine gene product. Using in situ hybridization on sections through frozen human tissues, we show that mRNAs for type 2 desmocollin are synthesized in various stratified epithelia such as epidermis, esophagus and exocervix, whereas type 1 desmocollin was detected in appreciable amounts only in epidermis. In addition, a striking difference has been observed within the epidermis, where type 2 desmocollin mRNA can be detected in several basal layers of living cells but type 1 desmocollin mRNA is restricted to suprabasal layers. The possible functional involvement of desmocollins in the differentiation of stratified tissues is discussed and the potential value of molecular probes for desmosomal cadherins in tumor diagnosis is emphasized. PMID- 8507557 TI - Two proto-oncogenes that play dual roles in embryonal cell growth and differentiation. AB - The function of growth factors in early development is reviewed. Special emphasis is on the epidermal growth factor and its receptor, and on the c-fos and its family of transcriptional factor proteins, which play an important role in modulating the growth and differentiation of early embryos and embryonal carcinoma cells. PMID- 8507558 TI - P19 embryonal carcinoma cells. AB - P19 cells are a line of pluripotent embryonal carcinoma able to grow continuously in serum-supplemented media. The differentiation of these cells can be controlled by nontoxic drugs. Retinoic acid effectively induces the development of neurons, astroglia and microglia--cell types normally derived from the neuroectoderm. Aggregates of P19 cells exposed to dimethyl sulfoxide differentiate into endodermal and mesodermal derivatives including cardiac and skeletal muscle. P19 cells can be effectively transfected with DNA encoding recombinant genes and stable lines expressing these genes can be readily isolated. These manipulations make P19 cells suitable material for investigating the molecular mechanisms governing developmental decision made by differentiating pluripotent cells. PMID- 8507559 TI - Embryonal carcinoma and the basement membrane glycoproteins laminin and entactin. AB - The mouse embryonal carcinoma lines PCC4-F and F9 have played important roles in the isolation and characterization of the two ubiquitous basement membrane proteins, laminin and entactin. The contributions of these cells to our work on extracellular matrices are briefly summarized. The in vitro differentiation of PCC4-F gives rise to a multiplicity of cell types. Two of these cell types have been propagated as cell lines. One of these, M1536-B3, synthesizes and deposits copious quantities of extracellular matrix glycoproteins, which led to the initial discovery and characterization of laminin and entactin. In addition, M1536-B3 provides a model system for analyzing the assembly of laminin and the laminin-entactin complex and for manipulating extracellular matrix structure and composition. The other cell line, 4CQ, synthesizes a matrix consisting of fibronectin and entactin. F9 cells differentiate to endodermal cells in response to retinoic acid and dibutyryl cyclic AMP (Strickland and Mahdavi, Cell 15: 393 402, 1978). The differentiated cells synthesize basement membrane components and provided the probes for the cDNA cloning of entactin and the three chains of laminin. The F9 cells have been widely employed to examine the regulation of expression of the laminin and entactin genes. PMID- 8507560 TI - Barry Pierce--why germ cells and germinal tumors? PMID- 8507562 TI - Epithelial-stromal interactions in colon cancer. AB - In this paper investigations concerning the interactions at the interface between tumor cells and tumor stroma are reviewed. As a model for tumor cell extracellular matrix interaction human colorectal carcinoma cell lines, in vitro and in vivo, in nude mouse xenografts, were chosen. Based on the available data and on a review of the literature the following conclusions can be drawn. Most malignant epithelial neoplasms at the site of tumor cell invasion display defects in the epithelial basement membrane. This is not merely the result of enzymatic dissolution but rather reflects a shift in basement membrane turnover towards degradation. Elsewhere in the same primary tumor or in a metastasis the balance might be shifted more towards basement membrane deposition. The tendency of a tumor to deposit basement membranes reflects the biological potential of the neoplasm. Basement membranes are deposited by stromal cells or by a concerted action of tumor and stromal cells. Differentiation in a carcinoma is modulated by factors in the extracellular matrix. Endocrine differentiation can be induced in vitro by native basement membranes but also by direct contact of the tumor cells with fibroblasts. Basic FGF is one of the extracellular matrix factors with differentiation inducing capacity. Expression of cell adhesion molecules and integrin receptors tends to be down-regulated in carcinoma cells. Alterations in the expression of these proteins might not be constitutive but rather modulated by the direct environment of the tumor cell and might not only include quantitative alterations but also changes in their cell surface distribution, causing or following loss of cell polarity. PMID- 8507561 TI - Midkine (MK), the product of a retinoic acid responsive gene, and pleiotrophin constitute a new protein family regulating growth and differentiation. AB - Using mouse teratocarcinoma system, we found a novel retinoic acid responsive gene. Midkine (MK), the product of the gene is a secreted, heparin-binding protein of molecular weight 14,000. MK gene is intensely expressed in the midgestation period, and in the adult mouse, the kidney is the principal site of its expression. MK and pleiotrophin have 50% sequence identity and constitute a new protein family regulating growth and differentiation. They share neurite outgrowth activity; other activities, either specific for one or common to both, have been reported. Furthermore, MK is of significant interest in cancer biology. PMID- 8507563 TI - G. Barry Pierce--mentor. PMID- 8507564 TI - Genomic plasticity of the Lucke renal carcinoma: a review. AB - The differentiation potential of the Lucke renal carcinoma of the northern leopard frog, Rana pipiens, can be characterized by the nuclear transplantation procedure. Transplantation of tumor nuclei into activated and enucleated ova results, in the best of cases, in swimming larvae which fail to feed. The larvae die in about 10 to 14 days. Rescue of tumor nuclear transplantation tadpole tissue, destined to die, has been accomplished by allografting fragments of that tissue to normal hosts. The allografts persist and differentiate a diversity of tissues which cannot be distinguished by histological analysis from allografted normal control tissue. Allografts are an imperfect mode of assay for histological competence because of the immune response of the host. Lymphocytes and eosinophils invade the grafts in about 40 days. The host immune response occurs in both experimental and control allografts. Consequently, we believe that added histogenetic potential exists in the genome of the Lucke renal carcinoma. We propose that unexpressed differentiative potential of the grafted tissue can be extracted by abrogation of the immune response of the host. A herpesvirus is the etiological agent of the Lucke renal carcinoma. We currently seek to detect viral DNA in tissue derived from tumor nuclear transplant embryos. The presence of the viral genetic material in normal mitotic progeny of Lucke tumor cells, if demonstrated, raises the question of the long-term stability of differentiated cells derived from a virus tumor. Alternatively, absence of viral DNA in the tumor nuclear transplant tissue would suggest that normal differentiation ensues after elimination of the oncogenic DNA from that tissue. Loss of viral DNA may prognosticate stable differentiation. PMID- 8507565 TI - Expression of E-cadherin in embryogenetic ingression and cancer invasion. AB - Homophilic interactions of E-cadherin serve the organization of embryonic and adult epithelia and counteract cancer invasion. The role of E-cadherin as an invasion-suppressor molecule has been demonstrated cancer. Regulation of embryonic ingression and cancer invasion via E-cadherin occurs at transcriptional, translational and post-translation levels. PMID- 8507566 TI - Studies on relationships between metastatic and non-metastatic tumor cell populations using lineages labeled with dominant selectable genetic markers. AB - The relationships between metastatic and non-metastatic cell populations co existing in composite neoplasms have been studied using cell lineages marked with a dominant selectable marker (neomycin resistance), by transfection. The experimental circumstances were arranged so that the lineages were known to be genotypically distinct (i.e. not merely phenotypic variants of the same lineage) and so that a single metastatic clone was each time combined with a mixed polyclonal non-metastatic population and both partners were distinctly and recognizably marked. This made it possible to ascertain the fates of clones with different metastatic capabilities during tumor progression and metastasis and evaluate their relative contributions to the clinical extent of disease. It was found that metastatic and non-metastatic cell lineages co-existed in most of the late-stage primary tumors examined and that a cell lineage that is invariably non metastatic, when growing on its own, can with surprising frequency be found thriving in distant metastatic deposits, when it grows to form a primary tumor in combination with a metastatic partner. In fact, occasional metastases from such tumors contained no detectable cells of the metastatic lineage. The endowment of a tumor cell lineage with a new, clinically significant, capability which it convincingly and reproducibly did not manifest before, by another coexisting cell population raises several new questions about the contribution of such phenomena to the overall debilitating properties of the neoplasm and the geometric progression of its impact on the host. PMID- 8507567 TI - Ontogeny, pathology, oncology. AB - This article traces the history of using embryo-derived stem cells for genetic manipulation--first teratocarcinoma stem cells and then embryonic stem cells. It encompasses several decades of research investigating the similarity between cellular mechanisms of normal growth and differentiation in the embryo and abnormal growth and differentiation in neoplasia. The limited developmental potential of teratocarcinoma-derived, embryonal carcinoma (EC) stem cells is contrasted to the totipotentiality displayed by embryonic stem (ES) cells derived directly from early embryos. From early attempts to select mutants in EC cells in culture to the spectacular success of targeting genes in ES cells by homologous recombination, the different lines of developmental, genetic and cancer research have converged to open vast new areas of possibility in genetic manipulation. PMID- 8507568 TI - Teratocarcinoma: neoplastic lessons about normal embryogenesis. AB - Germ cell tumors of the testis and the ovary have been studied extensively in humans and experimental animals. Murine teratocarcinomas proved to be one of the best experimental models for elucidating the histogenesis of these tumors and the nature of their undifferentiated stem cells. These spontaneous and experimentally induced tumors, especially those produced from early postimplantation stage embryos, provided a wealth of data about the differentiation of tumor stem cells and the regulation of their growth. This made it possible to draw parallels between the teratocarcinoma cells and their normal equivalents in the embryo. Cumulative data indicate that neoplastic development of murine embryonic cells is just one of the possible ontogenic pathways these cells can take while proliferating in various developmental fields. The malignancy of teratocarcinoma stem cells is determined genetically but can be regulated epigenetically. Development of stem cells in murine teratocarcinomas parallels events in the normal embryo, suggesting that events in the tumor have their normal regulatory counterparts in the embryo proper. The study of early embryos has provided data relevant for oncology, while the study of murine teratocarcinoma helped elucidate some basic developmental events occurring normally in the embryo. PMID- 8507569 TI - Extrinsic factors in cellular differentiation. AB - An impressive feature of cellular differentiation in metazoa is its stability. This has led to widespread acceptance of the view that the determined state is a heritable property of individual cells. There are, in fact, rather few types of cell for which this has been demonstrated convincingly. Not only is it clear that gene expression is subject to continuous regulation but there is also evidence for an increasing variety of cells that changes in differentiation can be induced by manipulating their environment. Such findings suggest that extrinsic factors may play a more significant role in maintaining the differentiated state of cells than is generally assumed. PMID- 8507570 TI - On the boundary between development and neoplasia. An interview with Professor G. Barry Pierce. Interview by Juan Arechaga. PMID- 8507571 TI - Regulators of normal development and tumor suppression. AB - Identification of normal growth and differentiation-inducing proteins and how they interact in normal development has made it possible to identify the molecular basis of normal development and the mechanisms that uncouple growth and differentiation so as to produce tumor cells. When normal cells have been changed into tumor cells, the malignant phenotype can again be suppressed. Results on the molecular control of growth and differentiation in normal myeloid hematopoietic cells, changes in the normal developmental program in myeloid leukemia, and the suppression of malignancy in myeloid leukemia and sarcomas, have shown that (A) malignancy can be suppressed either with or without genetic changes in the tumor cells, (B) suppression of malignancy by inducing differentiation does not have to restore all the normal controls, and (C) genetic abnormalities which give rise to malignancy can be bypassed and their effects nullified by inducing differentiation which stops cells from multiplying. PMID- 8507572 TI - The implications of a unified theory of programmed cell death, polyamines, oxyradicals and histogenesis in the embryo. AB - Programmed cell death (apoptosis) is the ubiquitous biological phenomenon of intentional cell death that eliminates redundant cells, changes phenotypic composition during histogenesis, provides form during morphogenesis and balances mitosis in renewing tissues. This form of cell death is controlled by a genetic program(s) that kills the targeted cell without causing subsequent inflammation. Malignant cells implanted into the appropriate regulatory field in the embryo will lose their malignant phenotype yet retain the capacity for proliferation and differentiation. This embryonic regulation of cancer requires simultaneous contact with specific structures on the surfaces of normal cells and exposure to soluble, extracellular signals. During studies to identify such soluble factors in the blastocyst, extracellular hydrogen peroxide was discovered in the blastocele fluid. Current evidence indicates that this hydrogen peroxide causes apoptosis of inner cell mass cells destined to develop into trophectoderm--the first apoptotic event during mammalian development which likely prevents the formation of ectopic trophectoderm in the soon-to-appear germ layers (histogenesis). The evidence also suggests that the hydrogen peroxide is generated during the oxidation of extracellular polyamines by a family of enzymes called amine oxidases. The components of this mechanism are also present in the mammalian epidermis, where they are proposed to control the survival of basal cell progeny and hence epidermal homeostasis (essentially controlling the production of tissue mass). This mechanism causes not only apoptosis in vivo, but also the unwanted and artefactual cell death in vitro known as the crisis of spontaneous transformation. These data suggest a novel link between polyamines and apoptosis, a link that has practical as well as theoretical implications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507573 TI - A peek at the future through histological preparations. AB - When histologists and pathologists examine histological preparations, they can often predict the future of tissues that have not been excised from bodies. This is possible because, unlike chemical and physical matter, living organisms travel in time on a genetically mandated fixed path. To recognize a portion of the path that tissues have already traveled, histological methods such as histochemistry and immunohistochemistry are effective. In this regard the development of the peroxidase-labeled antibody method (Nakane and Pierce, J. Histochem. Cytochem. 14:929-931, 1966) contributed immensely. For the portion of path which cells and tissues were traveling when they were removed from bodies, the method of choice is localization of mRNA by in situ hybridization. Specific methods designed to predict the future path of tissues are still at the drawing board phase. However, by discerning the past and current portions of the path and by referring to the paths that other tissues have traveled, one may deduce the future path of the tissues in question. For some time now, it has been my dream to develop methods enabling us to peek at the future path of tissues more concretely. To accomplish this one requires new procedural approaches. Thus, we would like to introduce in situ nick translation and oligonucleotide histochemistry. PMID- 8507574 TI - Stem cells and transgenic mice in the study of development. AB - In recent years, totipotent stem cells and transgenic mice have been widely used to understand the complex changes that occur during development, and these approaches underlie much of the dynamic growth in this field. The work of Barry Pierce in defining the multipotential characteristics of teratocarcinoma or embryonal carcinoma stem cells in the 1960s was an important milestone for the field and was instrumental in our choice of these cells for transfer into blastocysts in the first experiments designed to colonize a mouse with foreign totipotent cells. Following the development of transgenic techniques, the stem cell approach has become even more powerful, and during the past five years the combination of the two techniques has made possible the experimental creation of virtually any genetic change in mice, and ultimately in other species. In this review, the work in our laboratory over the past 30 years is summarized, and it reflects only a small part of the exciting array of experiments that have contributed to the explosive evolution of developmental biology during this period. PMID- 8507575 TI - [Tuberculin test--definition, materials, technique, interpretation]. PMID- 8507576 TI - [Poisonous and less poisonous plants. 7]. PMID- 8507577 TI - [Handling and preparation of cytostatic drugs]. PMID- 8507579 TI - [Nursing on its way to professionalization]. PMID- 8507578 TI - [For the best initial care of the newborn--thoughts on cooperation of obstetrics and pediatrics]. PMID- 8507580 TI - [80 years Albert Schweitzer Hospital in Lambarene]. PMID- 8507581 TI - Benefits of a structured peripheral arterial vascular rehabilitation program. AB - A structured vascular rehabilitation program is effective in relieving pain, improving function, and promoting optimal wellness. The rehabilitation program at the Vascular Institute of Florida uses supervised in-house exercise as well as a home maintenance program with follow-up. Extensive education and information on life-style factors are provided to the patient to normalize blood fats, control high blood pressure, stabilize blood glucose levels, reduce adverse stress, prevent progression of illness, and potentially prevent the progression of atherosclerosis to the arterial periphery. Ongoing research of structured exercise therapy and atherosclerotic risk factor behavior modification practices is crucial to the continued growth of vascular nursing. PMID- 8507582 TI - Effects of nutritional status on wound healing. AB - Malnutrition causes an array of metabolic alterations that affect wound healing. Stressed starvation, in which essential protein stores in lean body mass and viscera are utilized, is of utmost concern. Hospital-related malnutrition usually presents as a combination of both protein and energy malnutrition. Key nutrients play specific roles in wound healing. For example, vitamin C is essential for collagen synthesis, vitamin A enhances epithelialization, and zinc is necessary for cell mitosis and cell proliferation. Modern methods are available to determine an array of serum nutrient levels; however, these investigations are often inadequate, because serum levels of specific nutrients frequently do not reflect the total body content. Therefore the common association between generalized malnutrition and deficiencies of specific nutrients must be recognized. By using current nutritional techniques such as anthropometrics, albumin, transferrin, and immune status, one could determine nutritional deficiencies and thereby could replete all nutrients, including protein, carbohydrate, fat, vitamins, and minerals, through either parenteral or enteral support. PMID- 8507583 TI - Acute arterial occlusion of the lower extremity. AB - Acute arterial occlusion of the lower extremity occurs when blood supply from the lower limbs is abruptly cut off. Prompt evaluation and treatment are required to prevent irreversible damage. Differentiation between embolic and thrombotic sources is needed to initiate appropriate therapy. Although different types of occlusion require similar preoperative and postoperative considerations, the specific treatments vary. With a thorough understanding of the causes, signs and symptoms, treatment, and nursing management of acute arterial occlusion, the nurse can assist in the prevention of potentially severe complications. PMID- 8507584 TI - Venous ulcers, the nurse, and the health care budget. PMID- 8507585 TI - Making nursing research work for clients. PMID- 8507586 TI - Physician support for a vascular rehabilitation program: when, where, and how to get it. PMID- 8507587 TI - Right-eye transient blindness. PMID- 8507588 TI - Well-being and concerns of patients with peripheral arterial occlusive disease. AB - Peripheral arterial obstructive disease (AOD) affects an estimated 2.4 million persons in the United States, resulting in disability, morbidity, and even death in the elderly. Insight into the general well-being (GWB) of patients who have AOD can enhance the comprehensiveness of nursing care provided to these patients. GWB was examined in a study of 170 patients with peripheral AOD treated at a Veterans Affairs Medical Center (VAMC). The GWB instrument constructed by Dupuy and used extensively by the Rand Corporation was administered to provide an objective measure of well-being. Two open-ended questions regarding patients' concerns associated with their AOD provided more subjective information. The mean GWB score for the VAMC patients was lower than the mean score reported by the Rand Corporation for a group of healthy individuals, and this lent support to the construct validity of the instrument. The general health and vitality subscales appeared to have the widest difference in mean scores. Within the VAMC patient sample, GWB did not vary among age groups but did vary slightly in an inverse direction with the severity of the circulatory impairment. The concerns noted included fear of increased pain, lack of mobility, and fear of amputation. PMID- 8507589 TI - A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene. AB - The recessive-lethal, temperature-sensitive (ts) mutation of the tumor suppressor gene lethal(3)malignant brain tumor (l(3)mbt) causes in a single step the malignant transformation of the adult optic neuroblasts and ganglion mother cells in the larval brain at the restrictive temperature of 29 degrees C. The transformed cells are differentiation-incompetent and grow autonomously in a lethal and invasive fashion in situ in the brain as well as after transplantation in vivo into wild-type adult hosts. The imaginal discs show epithelial overgrowth. At the permissive temperature of 22 degrees C development is completely normal. The ts-period of gene activity responsible for 100% brain tumor suppression and normal imaginal disc development encompasses the first six hours of embryonic development. The l(3)mbt gene function is, however, also required thereafter for the proper differentiation of the brain and the imaginal discs. The l(3)mbt gene is located cytologically in the salivary gland chromosome bands 97E8-F11, and in molecular terms in 29 kb of DNA detected via a P-element insertional deletion. PMID- 8507590 TI - Differential expression and function of cadherin-like proteins in the sea urchin embryo. AB - Cadherins are Ca(+2)-dependent cell surface proteins involved in the specification of the adhesive properties of cells. They are supposed to play a critical role in morphogenesis and pattern formation. In this paper we show that in the sea urchin embryo there are at least two different cadherins of relative molecular masses 140 and 125 kDa. The 140 kDa cadherin is already present in the fertilized egg and is the sea urchin equivalent of E-cadherin. The 125 kDa cadherin, which can be detected using a broad-spectrum anti-cadherin antibody, appears only at later stages of development. In later embryos these two molecules are distributed differently: E-cadherin is present predominantly in the invaginating endoderm of the gastrula while the 125 kDa protein is present on the cell surface of most epithelia. Consistently with the observed differences in expression and in distribution, antibodies directed against these two cadherins differently perturb sea urchin development. For example, when these antibodies are added to early gastrulas only the antibodies against the 125 kDa component can induce a complete disaggregation of the ectoderm, while anti E-cadherin antibodies induce an abnormal development of the endoderm while the embryo maintains its basic integrity. These results are discussed in view of the need for multiple adhesion receptors during pattern formation and embryogenesis. PMID- 8507592 TI - Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part I. The role of aniline, benzidine, alpha-naphthylamine, and beta-naphthylamine. 1954. PMID- 8507591 TI - Low back pain in the workplace: attainable benefits not attained. PMID- 8507593 TI - A university's contribution to occupational health. AB - The first Chair of Occupational Health in the United Kingdom was established by Manchester University in 1945 and held by Ronald Lane, a consultant physician and experienced factor doctor. In his department, occupational medicine was taught as a clinical discipline to both undergraduates and postgraduates. Research was based mostly on clinical observation of workpeople in the field or as hospital outpatients. Although work has become less hazardous, with major risks like pneumoconiosis and lead poisoning brought under control by better occupational hygiene and more effective epidemiology, there is still much work related illness and injury. Promoting occupational health in its broadest sense still depends on clinical skills to assess fitness for work and to identify responses to adverse factors in the environment. A university department, through its teaching and research, needs to ensure that occupational health is practised as a clinical discipline. Opportunities for research are extensive and include: (1) identifying the extent and severity of injury and illness due to adverse environmental agents and psychosocial factors; (2) assessing fitness among the disabled and the elderly in an aging population enabling them to be gainfully or otherwise employed, (3) improving techniques for measuring work exposures and human responses to adverse work factors, and (4) evaluating intervention procedures. To fulfil its teaching and research commitments, an occupational health department has to maintain contacts with other disciplines in the university and with the industrial world outside. Isolation can be fatal. Academic departments of occupational health offer information to employers, trade unions, and health professionals seeking advice on health and safety problems. Such an Information and Advisory service provides topics for research and earns an income. It should not become the main activity otherwise teaching and research will suffer. PMID- 8507594 TI - Pre-employment lung function at age 16 years as a guide to lung function in adult life. AB - BACKGROUND: A study was conducted to find out if pre-employment lung function at age 16 improved the estimation of that between ages 25 to 27 compared with the use of reference values based on smoking history, stature, body mass index, and other concurrent anthropometric variables. METHODS: Apprentices attending a shipyard training school were assessed on six occasions from entry during their 17th year to age 25 to 27; results for 114 such men were analysed. The measurements were of stature, body mass, fat free mass and body fat, thoracic dimensions, forced expiratory volume and indices of forced expiratory flow, total lung capacity, and its subdivisions, transfer factor and KCO. RESULTS: At best about half the variance in the final lung function could be accounted for with the concurrent reference variables. For each lung function index the proportion of explained variance was substantially increased by also including in the prediction equation the pre-employment lung function expressed in standard deviation units. CONCLUSION: Estimation of the longitudinal decline in lung function during adult life should be based on initial and final measurements of which the first should ideally be at age 25 but those at age 16 can be used instead: such measurements have long term value and should be preserved. PMID- 8507595 TI - Prevalence of small opacities in chest radiographs of nickel sinter plant workers. AB - Radiographs from 745 nickel sinter plant workers were taken and classified by five readers using the International Labour Office (1980) protocol. Each reader worked independently and the films were randomly mixed with films from a non-dust exposed office population and also with films from subjects known to have silicosis or asbestosis. The prevalence of small irregular opacities was selected as the outcome of interest. In the sinter workers this was within the range identified in cigarette smokers or in workers exposed to dusts of low fibrogenicity. Only minimal evidence of small round opacities was noted. There was no evidence from the chest radiographs that exposures to high concentrations of dusts containing compounds of nickel caused an inflammatory or fibrogenic response in the lungs of the exposed population. PMID- 8507596 TI - Occupational exposure to dust and lung disease among sheet metal workers. AB - A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease. PMID- 8507597 TI - Respiratory symptoms, lung function, and pneumoconiosis among self employed dental technicians. AB - From the registry of self employed workers living in Paris, a group of 105 dental technicians was studied to evaluate occupational exposure, to determine respiratory manifestations, and to investigate immune disturbances. Seventy one dental technicians (age range 43-68: group D), 34 dental technicians younger than 43 or older than 68 (group d), and 68 control workers (age range 43-66: group C) were investigated. The demographic characteristics and the smoking habits of the groups D and C did not differ significantly. The dental technicians often worked alone (43.7%) or in small laboratories without adequate dust control. The mean duration of their exposure was long (group D 34.0 (SD 8.4) years). The prevalence of respiratory symptoms did not differ between groups D and C except for the occurrence of increased cough and phlegm lasting for three weeks or more over the past three years (group D 16.9%, group C 2.9%, p < 0.007). The effect of cigarette smoking on respiratory symptoms and lung function was obvious. All mean values of lung function for dental technicians and controls were within normal limits. Significant decreases in all mean lung function values were found among smokers by comparison with non-smokers, however, and a positive interaction with occupational exposure was established. The x ray films of dental technicians (n = 102, groups D and d) were read independently by four readers and recorded according to the International Labour Office classification of pneumoconioses. The prevalence of small opacities greater than 1/0 was 11.8% with a significant increase with duration of exposure. The prevalence among dental technicians with 30 years or exposure or more was significantly higher (22.2%) than those with less than 30 years (3.5, p < 0.004). The prevalence of autoantibodies (rheumatoid factors, antinuclear antibodies, and antihistone antibodies) was not significantly different in the groups D and C. When positive, autoantibodies only occurred at low concentrations. This finding contrasts with previous reports on the occurrence of autoantibodies and even of connective tissue diseases in dental technicians. In conclusion, the study confirms an increased risk of pneumoconiosis among dental technicians. Moreover, there may be other lung disorders such as impairment of lung function especially in association with cigarette smoking. PMID- 8507598 TI - Mortality and incidence of cancer in a cohort of Swedish chimney sweeps: an extended follow up study. AB - Despite 200 years of efforts to regulate safety in this occupation, chimney sweeps have increased mortality from cancer, ischaemic heart disease, and respiratory disease. Mortality and incidence of cancer were examined in a cohort of 5542 Swedish chimney sweeps employed through their national trade union at any time between 1918 and 1980. Previous studies of this cohort found increased risks of ischaemic heart disease, respiratory disease, accidental deaths, and various neoplasms. By increasing follow up, we sought to increase the power of the study and examine disease time trends. Mortality analysis was extended 7.5 years to cover the period 1951-90; cancer incidence analysis was extended six years to cover the period 1958-87. New findings include increased incidence and mortality of prostate cancer (SMR 169, 95% CI 106-256, 22 observed) and increased incidence of total haematolymphatic cancers (SIR 151, 95% CI 106-209, 36 observed). When only the most recent follow up period was analysed, previously observed risks persisted for total lung cancer (SIR 178, 95% CI 99-293), oat cell lung cancer (SIR 240, 95% CI 103-472), bladder cancer (SIR 247, 95% CI 131-422), and oesophageal cancer (Obs/Exp = 2/1.1). Mortality from ischaemic heart disease (SMR 98, 95% CI 76-123) and respiratory disease (SMR 111, 95% CI 56-199) declined during recent follow up, although significant excess mortality remained during analysis of the entire study period (ischaemic heart disease SMR 128, 95% CI 112 145; respiratory disease SMR 159, 95% CI 115-213). In analyses of the entire study period, risks of ischaemic heart disease and lung, bladder, and oesophageal cancer were adjusted for smoking; oesophageal cancer was also adjusted for use of alcohol. All risks remained significantly raised. Exposure-response analyses showed significant positive associations between duration of employment and risks for mortality from lung, oesophageal, and total cancer. Chimney sweeps remain at increased risk for cancers of the lung, oesophagus, and bladder. Our study supports a casual role for exposure to chimney soot, which contains carcinogens including polycyclic aromatic hydrocarbons. Extended follow up of this cohort now shows increased risks of prostate and haematolymphatic cancers. PMID- 8507599 TI - Application of the urinary S-phenylmercapturic acid test as a biomarker for low levels of exposure to benzene in industry. AB - Recently, the determination of S-phenylmercapturic acid (S-PMA) in urine has been proposed as a suitable biomarker for the monitoring of low level exposures to benzene. In the study reported here, the test has been validated in 12 separate studies in chemical manufacturing plants, oil refineries, and natural gas production plants. Parameters studied were the urinary excretion characteristics of S-PMA, the specificity and the sensitivity of the assay, and the relations between exposures to airborne benzene and urinary S-PMA concentrations and between urinary phenol and S-PMA concentrations. The range of exposures to benzene was highest in workers in chemical manufacturing plants and in workers cleaning tanks or installations containing benzene as a component of natural gas condensate. Urinary S-PMA concentrations were measured up to 543 micrograms/g creatinine. Workers' exposures to benzene were lowest in oil refineries and S-PMA concentrations were comparable with those in smoking or nonsmoking control persons (most below the detection limit of 1 to 5 micrograms/g creatinine). In most workers S-PMA was excreted in a single phase and the highest S-PMA concentrations were at the end of an eight hour shift. The average half life of elimination was 9.0 (SD 4.5) hours (31 workers). Tentatively, in five workers a second phase of elimination was found with an average half life of 45 (SD 4) hours. A strong correlation was found between eight hour exposure to airborne benzene of 1 mg/m3 (0.3 ppm) and higher and urinary S-PMA concentrations in end of shift samples. It was calculated that an eight hour benzene exposure of 3.25 mg/m3 (1 ppm) corresponds to an average S-PMA concentration of 46 micrograms/g creatinine (95% confidence interval 41-50 micrograms/g creatinine). A strong correlation was also found between urinary phenol and S-PMA concentrations. At a urinary phenol concentration of 50 mg/g creatinine, corresponding to an eight hour benzene exposure of 32.5 mg/m3 (10 ppm), the average urinary S-PMA concentration was 383 micrograms/g creatinine. In conclusion, with the current sensitivity of the test, eight hour time weighted average benzene exposures of 1 mg/m3 (0.3 ppm) and higher can be measured. PMID- 8507601 TI - Bibliography for ophthalmic plastic surgery. PMID- 8507600 TI - Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans. AB - This study was designed to clarify the nature of effects of trichloroethylene (TCE) on the central nervous system, and to determine the critical concentrations in blood associated with specific behavioural changes. This was achieved by a follow up of the whole time course of TCE intoxication during and after exposure. The effects of a single four hour exposure to TCE on signalled bar press shock avoidance in rats were tested by methods previously applied to investigate the acute neurobehavioural effects of exposure to toluene. Even low exposure to TCE induced shock avoidance performance decrements in rats. Rats exposed to 250 ppm TCE showed a significant decrease both in the total number of lever presses and in avoidance responses at 140 minutes of exposure compared with controls. The rats did not recover their pre-exposure performance until 140 minutes after the exhaustion of TCE vapour. Exposures in the range 250 ppm to 2000 ppm TCE for four hours produced concentration related decreases in the avoidance response rate. No apparent acceleration of the reaction time was seen during exposure to 1000 or 2000 ppm TCE. The latency to a light signal was somewhat prolonged during the exposure to 2000 to 4000 ppm TCE. It is estimated that there was depression of the central nervous system with slight performance decrements and the corresponding blood concentration was 40 micrograms/ml during exposure. Depression of the central nervous system with anaesthetic performance decrements was produced by a blood TCE concentration of about 100 micrograms/ml. These results showed effects of TCE on the central nervous system that were considered to be a function of both the exposure concentration and the duration of exposure, which are closely related to the TCE concentration in blood. PMID- 8507602 TI - [In new times, new things and facts]. PMID- 8507603 TI - [The hyperbaric method in the treatment of diabetic retinopathy, an alternative to laser therapy?]. AB - The hyperbaric oxygen inhaled at the pressure od 2-3 atmospheres raises considerably the blood concentration of the gas, which becomes sufficient for tissular needs sometimes without soliciting hemoglobin intervention. This makes possible the survival of some tissues insufficiently supplied with blood. We forecast therapeutical indications in diabetic retinopathy, hypertensive retinopathy, retinal venous obstructions, Eales disease. In proliferative diabetic retinopathy the hyperbaric oxygen might substitute the laser therapy. PMID- 8507604 TI - [The incidence of different forms of eye trauma at the Clinica Oftalmologica Cluj Napoca]. PMID- 8507606 TI - [A morbidity study of intraocular foreign bodies]. AB - 190 patients presenting intraocular foreign bodies, hospitalized between 1981 1991, are examined. The study of accidents: cases showed a clear prevalence of work accidents--127 cases (66.84%); 86 of these cases occurred in industry (45.26%), the rest of 41 occurred in agriculture (21.58%). The professions most exposed to such accidents are those of locksmith, mechanic in agriculture or automobile industry. The postsurgical evolution and the incidence of complications show that intraocular foreign bodies are wosse-making factors of ocular plagues, because of anatomical structures disorganization, transparency modifications and infectious complications implied, which determined the diminishing of visual acuity in 88.08% of cases. The big percentage of work accidents in the etiology of intraocular foreign bodies emphasize the great importance of foreign the work-protection rules (regarding a especially the wearing of protection glasses) and of introducing of automation in technological processes involving great risks. PMID- 8507605 TI - [The early changes in the fundus oculi of premature infants]. AB - The authors prospect the fundus at 69 prematures with birth weight under 1,500 g and at 49 prematures with birth weight over 1,600 g, whose neonatal pathology required intermittent administration of oxygen. The examination were done at the medium age of 5.5-6.9 weeks, when the retinal development is completed. The results show a greater proportion of the nervous systems lesions and of the retinopathy at the prematures with birth weight less than 1,500 g, in similar conditions of oxygen administration and prophylaxis with E-vitamin. It is indicated the opportunity of fundus investigation at all the prematures with very low birth weight and the necessity of prophylactic administration of E-vitamin starting from the first day of life. PMID- 8507608 TI - [Optical correction in accommodative convergent strabismus]. AB - The accommodative strabismus is quite frequent. The refraction vices correction can lead to ocular axis parallelism. It is advisable that refraction measurement to be done after prolonged cycloplegia using 1% atropine and spectacles prescription to be made as close as possible to the value of refraction. Prismatic correction is recommended in heterophorias, the prismatic values must be under 6 prismatic diopters for each eye. PMID- 8507607 TI - [The morphological forms of malignant uveal melanoma]. AB - They are presented the histopathological forms of the uveal malignant melanoma, its characteristics in electronic microscopy and also an attempt to correlate the histological type with the vital prognosis. They are reviewed the main classifications of this uveal malignant tumour, elaborated over time, and the criteria used for their establishment by the authors. PMID- 8507609 TI - [Dacryocystorhinostomy in children]. AB - During the last ten years 218 dacryocystorhinostomies were done, 8 of them on under 10-years-old children (3.7%). Dacryocystorhinostomy remains the only curative intervention which may be done on children even when the lacrimal ways sounding is inefficient. The surgical technique was the same as the one used for the adults, with some characteristic features imposed by the age of the patient. The intervention was some especially on children with congenital imperforations of the lacrimo-nasal channel, when the repermeability of the lacrimal ways could not be obtained by repeated soundings, but also in traumatic and congenital malformed dacryocystitis. The operation was made with good results even after the extirpation of the lacrimal sac, followed by the formation of a neosac. In the observations we presented the underlimit of the intervention has been 2 years and 4 months. PMID- 8507610 TI - [Therapeutic failures in indirect injuries to the optic nerve]. AB - Making an analysis during five years, the authors find a great number of atrophies of optic nerve after indirect trauma on the orbital area or an the head, questioning if the treatment applied had been correct. Studying the literature they find the same feeble results and controversial opinions regarding the therapy of these cases. On tried treatments with macrodoses of dexamethazone i.v., the opening of optic nerve's health or of the optic nerve's duct, the vacating of the retrobulbar haematomas, but the results remained unsatisfying. The problem is if we must console ourselves that the others have the same feeble results or we must try to add to the conservatory treatment applied till now the neurosurgical investigations of the optic duct and heaths of the optic nerve, especially when the vision is lowering progressively and especially when the other eye is also implied. PMID- 8507611 TI - [Surgery of concomitant strabismus with an adjustable suture]. AB - The authors emphasize the main features of the "adjustable suture" in concomitant strabismus surgery. Good results (over 92% of orthotropia) were noted especially in very young children (under 3 years of age)--cases in which an exact study on the status of motricity and vision is not possible. PMID- 8507612 TI - [Penetrating orbital wounds with retention of the plant foreign bodies]. AB - Here are presented the clinical observations of 5 patients with these diagnosis. We discussed the necessity of attentive exploration of the orbital injuries in the moment of urgency interventions because the foreign bodies can be multiplied. It is also important to suspect the retention of wood foreign bodies in the orbit in the presence of the patients: orbital fistula with an orbital injury in their antecedents. PMID- 8507613 TI - [Keratopathy due to a spray]. AB - The paper presents seven cases of corneo-conjunctival lesions produced by anti aggressional spray. The corneal lesions were superficial and do not exceed in depth the Bowman membrane. Besides the ocular lesions, the patients presented irritative cough and general manifestations represented by a transient motor deficit, which produced the decrease of the defense capabilities during 15-30 minutes. The ocular lesions had a favourable evolution, excepting two cases with more severe evolution. PMID- 8507614 TI - [Posttraumatic blood clot in the anterior chamber--the therapeutic problems]. AB - Blood presence in anterior chamber in coagulated form raises special therapeutical problems. Even when the blood pressure is normal, it is not allowed to wait too much, because the clot doesn't have the tendency of fast resorption. They are emphasized the surgical difficulties, caused by a too large opening and by adherence of the clot to the iris, capsule of the lens and hyaloid, the necessity of use of a spatula for the detachment of the clot in case the urokinasis may not be used. PMID- 8507615 TI - [Ocular accidents from the breaking of windshields]. AB - A survey of 502 cases of ocular plagues, hospitalized in a 5-years period shows 5 cases produced by windscreen cracking. To avoid such accident compulsory the use of life-bear, even in short city departures. It is advisable that the windscreen to be made of lamellar glass (triplex), which produces less ocular lesions than "security" glass. PMID- 8507616 TI - [Progressive external ophthalmoplegia and distal myopathy]. AB - A patient, 58 years old, presents progressive blepharoptosis, in both eyes and external ophthalmoplegia. The general somatic examination, shows, at the level of the higher limbs, distal myopathy with muscular hypotony and articular deformities fibrosis and tendinous retraction. On examining the eye bottom we found colloid degeneration in the muscle region. Within the same family a ten year-old nephew presents congenital ptosis. The muscular biopsy from the levator palpebrae shows muscular degenerative lesions with the reduction of nuclei and the proliferation of conjunctive tissue. It is shown that progressive external ophthalmoplegia must be interpreted as an ocular myopathy. The association with the distal myopathy at the level of the higher limbs, in the presented observation, upholds this pathogeny. PMID- 8507617 TI - [Perforated corneal ulcer after recurrent herpetic keratitis]. AB - The paper presents a case of spontaneous perforation of the cornea happened on an eye with neglected relapsed herpetic keratitis. It is discussed the role of corticotherapy, local toxicity of used antiviral drugs and neurotrophic troulles in the territory of the ophthalmic nerve, as being factors which could have hurried up the evolution towards the perforation. The relapses specific to infections with herpes simplex are favoured by the cantonment of the virus, in latent state, in the trigeminal ganglion but also possibly in the ocular tissues (including the cornea). The use of corticosteroids in deep herpetic keratitis must permanently have in view the possibility of persistence of the virus in the corneal tissue. PMID- 8507618 TI - [The therapeutic prospects in glaucoma treatment]. AB - The appearance of new drugs in glaucoma's treatment has the aim to reduce the ocular hypertonia and to preserve the visual field maintaining the integrity of visual fibres which form the optic nerve. The authors review the drugs which have action on the trabeculum, such as parasympathomimetics, adrenalin, glicocorticoid antihormones and colchicine, also influencing the ciliary processes as inhibitors of carbonic anhydrase, and the drugs which have an action on the uveoscleral paths such as prostaglandines. PMID- 8507619 TI - [Ocular trauma in children]. AB - The authors study etiopathogenic clinical and therapeutic features of ocular injuries on a group of 175 children hospitalised and treated in the Department of Ophthalmology from Municipal Clinical Hospital of Bucharest. The study includes also the immediately and belated sequels. PMID- 8507620 TI - [The characteristics of general anesthesia in ocular surgery]. AB - The general anesthesia is recommended in ocular surgical interventions on children or patients with psychical lability, anxiety and in general intervention on open globe. Before the intervention, a permanent contact between the ophthalmologist and the anesthesiologist is necessary, in order to manage the complexity of the case and to adopt a common attitude. The attitude which has to be taken to avoid the pre- and post-operational incidents is put into light. PMID- 8507622 TI - [Ocular complications in zona ophthalmica]. AB - 81 cases of herpes zoster ophthalmicus with ocular affection, hospitalized in the clinic of ophthalmology between 1980-1991, are presented. The most frequent ocular complications were dendritic keratitis and punctate epithelial keratitis in 12 cases, neurotrophic keratitis in 7 cases, keratoendothelitis in 22 cases, iritis and iridocyclitis in 26 cases posterior uveitis in 3 cases. Seldom complications, presented each with a single case, were secondary glaucoma, optical postnevritical atrophy, oculomotor nerves palsy. The lesions were equally distributed between the two eyes. The associations of these complications determined visual acuity diminishing below 1/10 in 27 cases. In spite of association of classical treatment with recent antiviral medication and due to serious ocular complications which appear at most of 50% of the patients with herpes zoster ophthalmicus, the functional prognosis remains reserved. PMID- 8507621 TI - [The action of the supernatants from human lymphocyte cultures on E-active rosette formation]. AB - Lymphocytes separated from 20 normal subjects were introduced in two rosetation systems: the first was modulated rosetation (REM) with phytohemaglutinina (PHA), concanavalina A (Con. A). Mycobacterium tuberculosis (Mbt), and tumoral extract from ocular malignant melanoma (ET-MMO): the second was E-active modulated rosetation with supernatants from human lymphocyte cultures stimulated with PHA, Con A, Mbf and ET-MMO (REM-S), he average values of percentages of rosettes forming cells in the two systems REM and REM-S are comparable. We may assume the existence of some modulating factors which operate in the same manner on the functionality of T-lymphocyte in the two systems (REM and REM-S). PMID- 8507623 TI - [The artificial lens implant]. AB - The paper presents a short history of the cataract intervention, starting from the lens luxation in vitreum and going to the implant of artificial lens. From the three classes of artificial lenses, up-to-date options are the posterior chamber artificial lenses. Today, in 80% of the cases, artificial lens implant is done, 80% of the implanted lenses being posterior chamber lenses. The paper also exposes various operatorial techniques, post-operatorial evolution and the results obtained. PMID- 8507624 TI - [Monophthalmia and automobile driving]. AB - The estimation of the visual abilities of monophtalmic patients must be done individually and the driving licence must be released only after careful consideration of all the anatomo-functional aspects of the eye in connection with the functional state of the nervous system. For releasing the driving licence to monophthalmic patients are proposed to be done: the determination of the kinetical visual acuity, the exam of the stereoscopic vision and the effectuation of some psychological tests by the ophthalmologist. PMID- 8507625 TI - [Normal and pathological conjunctival cytology]. AB - The authors propose a cytological study of the conjunctiva, using the conjunctival print method, at patients with different (degenerative inflammatory and tumoral) ocular diseases. The conjunctival print method is less traumatic and contributes, together with the data supplied by the clinical examination, in elucidating the etiological diagnosis and orientating therapeutical conduct. Without representing a pathognomonic exam, the cytological study of the conjunctiva brings important diagnosis data, but also data concerning the evolution, so it is recommended to be done in the dynamics. PMID- 8507626 TI - [Reintervention after scleral sub volet trabeculectomy]. AB - The paper refers to the efficiency of reinterventions on eyes with glaucoma already operated but in which the drainage surgery has become inefficient in time. The reintervention consists of going through the access paths obtained at the first intervention, cauterizing the scleral vessels adjacent to the protection volet and making the cyclodialysis. The results are lasting until now, the intervention is simple and rational, without special intra- or post operatorial complications. PMID- 8507627 TI - [The surgical approach to invasive orbital tumors]. AB - The orbital exenteration is less and less practiced today, because of the reduced pathology which may impose such a radical intervention, but also because it has been transferred, in the lest two decades, to the maxillofacial plastic surgery. The paper presents three orbital exenterations, accomplished in the spinous-cell carcinoma of the inferior eye lid invading in the orbit, basal-cell epithelioma of internal angle recidivated during repeated interventions and conjunctival malignant melanoma invading the orbit. It is shown that orbital exenteration must not to abandoned by the ophthalmologists, which are the first doctors contracted by these patients and the only ones which can decide when the ocular globe may be sacrificed, with a recovery of the region as aesthetic as can be. PMID- 8507628 TI - [Intracranial hypertension and tetracycline therapy]. AB - The paper focuses on the possibility of turning up, to a patient suffering of acne during a long treatment using tetracycline, of some alarming neurological modifications accompanied at the eye fundus examination by stasis papillar oedema. The interruption of treatment leads to the disappearance of the whole set of clinical phenomena and modifications of depicted ocular symptoms. PMID- 8507629 TI - [Cortisone-related glaucoma]. AB - The cortisonical treatment has been more and more used in the last years, with an anti-inflammatory purpose, in ocular and general affections. The most severe ocular complications due to the prolonged treatment are the cortisonic glaucomas and the cortisonic cataract, both determining serious alterations of the visual function. The paper present the case of a patient, female, who was diagnosed five years before with pemphigus vulgaris, for which she has followed a prolonged cortisonic treatment. The ophthalmological examination has revealed the association with an open angle glaucomas and with a cortical posterior cataract, both having as a possible cause the prolonged prednisonic treatment. In order to prevent the affection we have to impose both the good judgement in prescribing the cortisonic medication and the periodical control of intraocular pressure in prolonged corticotherapy. PMID- 8507630 TI - [The organization of the screening and treatment of strabismic children in the city of Oradea and Bihor County]. PMID- 8507631 TI - [The prevention of blindness and amblyopia]. PMID- 8507632 TI - Graves' ophthalmopathy. AB - The Graves' ophthalmopathy consists of all the pathological changes in orbital tissues, preceding, accompanying of following hyperthyroidism. Although ophthalmopathy has its clinical expression only in 50% of patients with Graves disease, the ultrasound exploration and the CT scan of the orbital area, as well as the values of intraocular pressure showed that occult changes exist in all patients. The etiopathological autoimmune mechanism responsible of ophthalmopathy doesn't imply the same autoantibodies, though ophthalmopathy is associated with thyrotoxicosis, and the degree of ocular changes is not related to the level of autoantibodies directed against the TSH receptors nor to the level of antibodies involved in thyroid cells' growth. It occurs that there exist two different autoimmune mechanisms. The ocular prognosis depends on the amplitude and the duration of the ocular changes, the functional state, the presence of complications. Good results are conditioned by the precocity of the treatment. The treatment in Graves' ophthalmopathy consists of local and endocrinological treatment. PMID- 8507633 TI - Measured change in protein solvation with substrate binding and turnover. AB - Osmotic stress is used to measure solvation changes that accompany the conformational changes of an active enzyme. For hexokinase both the equilibrium dissociation constant and the kinetic Michaelis-Menten constant for glucose vary linearly, and to the same extent, with the activity of water in the protein medium, as adjusted with large molecular weight (> 2000) osmolytes. The variation over the whole osmotic pressure range studied indicates that glucose binding is accompanied by the release of at least 65 +/- 10 water molecules, and this is reversed on enzyme turnover. The results indicate that near the physiological range of pressures the number may be higher. Most of this water, which behaves like an inhibitor, likely comes from the cleft which is induced to close around the substrate. Such large dehydration/rehydration reactions during turnover imply a significant contribution of solvation to the energetics of the conformational changes. Osmotic stress is a method of general applicability to probe water's contribution to functioning molecules. PMID- 8507634 TI - Mass spectrometric identification of phosphorylation sites in bleached bovine rhodopsin. AB - Deactivation of the visual cascade is initiated by the phosphorylation of rhodopsin. We report here identification of the two major sites of phosphorylation in bleached bovine rhodopsin using tandem mass spectrometry in conjunction with synthetic phosphopeptide standards. Both bleached and unbleached rod outer segments were cleaved with endoproteinase Asp-N to release the C terminal fragment, residues 330-348, containing seven potential sites of phosphorylation. High-performance liquid chromatographic separation of soluble cleavage products from both unbleached and bleached rod outer segments gave a peak which was identified by tandem mass spectrometry and comparison to synthetic standards as monophosphorylated (serine 338) DDEASTTVSKTETSQVAPA. Present only in the chromatogram of bleached ROS were two peaks identified as monophosphorylated (serine 343) and diphosphorylated (serines 338 and 343) derivatives of DDEASTTVSKTETSQVAPA. These results identify serines 338 and 343 as the major sites of phosphorylation within the C-terminal region of bleached bovine rhodopsin and constitute the first example of mass spectrometric characterization of phosphorylation sites in a G-protein coupled receptor. PMID- 8507635 TI - Processive interfacial catalysis by mammalian 85-kilodalton phospholipase A2 enzymes on product-containing vesicles: application to the determination of substrate preferences. AB - Substrate specificities of the human and rat kidney 85-kDa phospholipase A2 enzymes (hmw-PLA2) have been determined under conditions in which hydrolysis of substrate vesicles occurs without the desorption of enzyme from the interface (scooting mode catalysis). The rat kidney enzyme binds to vesicles of 1-oleoyl-2 palmitoyl-sn-glycero-3-phosphocholine (OPPC), which contain the substrate 1 stearoyl-2-arachidonyl-sn-glycero-3-phosphocholine (SAPC) and 10 mol% arachidonic acid (20:4) and 1-stearoyl-sn-glycero-3-phosphocholine (S-lyso-PC) as the hydrolysis reaction products, with a second-order rate constant k(on) approximately equal to 2 x 10(7) M-1 s-1. Upper limits of k(off) < or = 3 x 10( 4) s-1 and KD < = or 15 pM for the dissociation rate and equilibrium constants, respectively, are estimated from the vesicle binding measurements. The initial rates of hydrolysis of either radiolabeled 1-stearoyl-2-arachidonyl-sn-glycero-3 phosphoserine (3H-SAPS), -phosphoethanolamine (3H-SAPE), -phosphoinositol (14C SAPI), or -phosphate (3H-SAPA) and either 3H-SAPC or 14C-SAPC, which were incorporated into product-containing OPPC vesicles, were simultaneously measured with dual isotope radiometric assays. The plasmenylcholine 1-O-(Z-hexadec-1' enyl)-2-arachidonyl-sn-glycero-3- phosphocholine (3H-PlasAPC) was also tested. Relative substrate specificity constants (Kcat/KM* values) were determined from the concentrations and initial rates of hydrolysis of the labeled substrates; the rank order of the values is SAPC approximately equal to SAPI approximately equal to PlasAPC > SAPE > SAPA approximately equal to SAPS. The maximal difference in specificity constants is 3.5-fold, indicating that the hmw-PLA2 does not significantly discriminate between phospholipids with different polar head groups. The diglyceride 1-stearoyl-2-arachidonyl-sn-glycerol is not a substrate for the human hmw-PLA2. Two mixtures of 1-stearoyl-2-acyl-sn-glycero-3 phosphocholine, which have different sn-2 acyl chains, were prepared and compared to SAPC as substrates. One mixture contained naturally-occurring unsaturated fatty acyl chains and the other contained a mixture of 20:4, all of its partially hydrogenated analogues (20:3, 20:2, and 20:1), and arachidic acid (20:0). The order of preference for the human hmw-PLA2 is sn-2-20:4 > sn-2-alpha-linolenoyl > sn-2-linoleoyl > sn-2-oleoyl > or = sn-2-palmitoyleoyl.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8507636 TI - Characterization of the thermolysin-like cleavage of biologically active peptides by Xenopus laevis peptide hormone inactivating enzyme. AB - Peptide hormone inactivating endopeptidase (PHIE) is a metalloendopeptidase which was isolated from the skin granular gland secretions of Xenopus laevis [Carvalho, K. M., Joudiou, C., Boussetta, H., Leseney, A. M., & Cohen, P. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 84-88]. This peptidase exhibits a thermolysin-like character and hydrolyzes bonds on the amino terminus of hydrophobic amino acids, performing cleavage of Xaa-Phe, Xaa-Leu, Xaa-Ile, Xaa-Tyr, and Xaa-Trp doublets. When the enzyme recognized a doublet of hydrophobic amino acids such as Phe6-Phe7 of somatostatin-14, Phe7-Phe8 of substance P, Phe4-Leu5 of [Leu5,Arg6]enkephalin, and Tyr4-Ile5 of angiotensin II, cleavage occurred preferentially between these residues. The use of selectively modified carboxy-terminal octapeptide fragments of atrial natriuretic factor (ANF) indicated that the enzyme tolerates as substrates only peptides bearing a P'1 bulky hydrophobic amino acid residue. Although a P'1 hydrophobic residue was a necessary condition, it was found in a number of peptides that all potential cleavage sites were not recognized by the enzyme. These data suggested that this metalloendoprotease requires for its thermolysin-like activity a preferred conformation of the peptide chain. Kinetic results obtained using a series of related substrates derived from biologically active peptides of the atrial natriuretic factor, tachykinin, and enkephalin families indicated the presence of an extended binding site accommodating at least six amino acid residues, in contrast to thermolysin (EC 3.4.24.4) and neutral endopeptidase (NEP; EC 3.4.24.11), which hydrolyze shorter homologous peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507637 TI - Directed mutagenesis and barnase-barstar recognition. AB - Directed mutagenesis has been applied to the cloned genes of barnase and barstar, the extracellular ribonuclease of Bacillus amyloliquefaciens and its intracellular inhibitor, to locate residues involved in the mutual recognition of these two proteins. Arg59 and His102 of barnase and Asp35 and Asp39 of barstar have been so identified. With both Cys40 and Cys82 mutated to alanines, barstar is still produced in high yield and is functional both in vitro and in vivo. Methods devised for determining relative and absolute dissociation coefficients for various combinations of mutant and wild-type proteins have allowed us to determine a dissociation coefficient for the complex of wild-type barnase and barstar of about 10(-13) M, with off and on rate constants of 10(-5) s-1 and 10(8) M-1 s-1, respectively. PMID- 8507638 TI - Molecular characterization of a conserved, guanine nucleotide-dependent ADP ribosylation factor in Drosophila melanogaster. AB - ADP-Ribosylation factors (ARFs) are ubiquitous approximately 20-kDa guanine nucleotide-binding proteins that stimulate cholera toxin-catalyzed ADP ribosylation in vitro. Because the functional role(s) of ARF in mammalian systems is (are) elusive, we looked for ARF in Drosophila melanogaster, and report the partial purification and molecular cloning of an ARF from Drosophila. We cloned the Drosophila ARF 1 gene without library screening by a combination of 5 polymerase chain reactions (PCRs), yielding a 546-base open reading frame encoding 182 amino acids, which are > 93% identical to those of mammalian class I ARFs. This ARF gene maps to 79F3-6 in the proximal region of the left arm of Drosophila chromosome 3. The Drosophila ARF1 gene structure, including placement of introns, is highly conserved relative to mammalian class 1 ARF genes. A single ARF mRNA species of 1.8 kb was abundant in all Drosophila body segments. Recombinant Drosophila ARF 1 synthesized in Escherichia coli had biochemical and immunochemical activities similar to those of mammalian ARF. The similarities of sequence and biochemical properties between Drosophila and mammalian ARFs contrast with their differences from Drosophila arl (ARF-like protein), which does not stimulate cholera toxin-catalyzed ADP-ribosylation, and is only approximately 52-56% identical in amino acid sequence to mammalian ARFs. PMID- 8507639 TI - NMR studies of the POU-specific DNA-binding domain of Oct-1: sequential 1H and 15N assignments and secondary structure. AB - The 1H and 15N resonances of the POU-specific DNA-binding domain of transcription factor Oct-1 have been assigned sequentially using two-dimensional homo- and heteronuclear NMR techniques, as well as three-dimensional heteronuclear NMR techniques, including TOCSY, 2D NOE, and NOESY-HMQC experiments. A number of typical short- and medium-range NOE contacts, as well as amide proton exchange data, gave evidence for the presence of four alpha-helices, in the peptide segments 1-19, 23-34, 40-49, and 54-71, which are connected by short loops of irregular structure. Interestingly, the second helix contains three glycine residues and the fourth helix a proline in the middle of the helix. Although the regular pattern of hydrogen bonds in the fourth helix is interrupted, due to the absence of an amide proton in proline, the helix is remarkably stable. All four helices are amphipathic, which suggests a packing of the apolar sides of the helices in the folded structure of the protein. PMID- 8507640 TI - Structural and functional characterization of sperm whale myoglobin mutants: role of arginine (E10) in ligand stabilization. AB - 1H NMR and ligand-binding data were used to assess the role of residue Arg(E10) in ligand stabilization of several site-directed mutants, all carrying the His(E7) to Val substitution, obtained using a synthetic sperm whale myoglobin gene. Arg(E10) was previously found to form a hydrogen bond with the ligand in fluoro-, azido- and cyanomet derivatives of Aplysia limacina myoglobin, which lacks the distal His(E7) [Qin, J., La Mar, G. N., Ascoli, F., Bolognesi, M., & Brunori, M. (1992) J. Mol. Biol. 224, 891-897]. NMR analysis of the paramagnetically induced relaxation, hyperfine shift patterns, and dipolar connectivities shows that Arg(E10) also falls into the distal pocket in the engineered sperm whale myoglobin mutants and resides at an H-bonding distance from the Fe(3+)-bound cyanide. The rate constant for cyanide dissociation from the ferrous derivative was determined by stopped-flow experiments; the ligand stabilization achieved by Arg(E10) is similar to that exerted by His(E7) in wild type sperm whale myoglobin, and both are very different from the His(E7)Val single mutant. Contrary to that for the wild-type, the cyanide dissociation rate constant for the mutant containing Arg(E10) is essentially independent of pH (from 6 to 9), as expected on the basis of the guanidinium group of Arg having a pK > 10. This finding is consistent with the NMR data in which the chemical shift of the Arg(E10) N epsilon H is insensitive to pH (6-9), as is also observed in Aphysia limacina cyanometmyoglobin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507641 TI - Structure of human parathyroid hormone(1-34) in the presence of solvents and micelles. AB - The structure of the N-terminal 34-residue fragment of human parathyroid hormone was determined in 40% trifluoroethanol employing two-dimensional 1H nuclear magnetic resonance spectroscopy. The proton chemical shifts were assigned from magnitude and phase-sensitive COSY, relayed COSY, and NOESY spectra. Distance constraints, estimated from NOESY spectra, were used to create a set of structures by distance geometry (DGEOM) which were subsequently refined by restrained energy minimization and restrained molecular dynamics (CHARMm). The resulting structures contained two helices spanning residues 3-12 and residues 17 26. The NOE constraints for residues 13-16 did not provide a single structural solution; however, their conformations were not disordered. The structures prepared by DGEOM and refined with CHARMm contained either an irregular turn or a helical structure at residues 13-16. The secondary structure of human parathyroid hormone(1-34) was also assessed by circular dichroism in the presence of methanol, trifluoroethanol, and dodecylphosphocholine micelles. Under all three conditions, the peptide formed structures containing various amounts of helical content. The formation of helical secondary structure in the presence of micelles supports the proposal that the trifluoroethanol-induced structure of human parathyroid(1-34) was not an artifact of its environment but perhaps was an indication of the conformation that the molecule adopts when in close proximity to a membrane surface and possibly when bound to the parathyroid receptor. PMID- 8507642 TI - Importance of protein rearrangement in the electron-transfer reaction between the physiological partners cytochrome f and plastocyanin. AB - Cytochrome f from turnip and plastocyanin from French bean were noninvasively cross-linked in the presence of the carbodiimide EDC so that the exposed heme edge in the former protein abuts the acidic patch remote from the copper site in the latter [Morand, L.Z., Frame, M.K., Colvert, K.K., Johnson, D.A., Krogmann, D.W., & Davis, D.J. (1989) Biochemistry 28, 8039]. The molecular mass, reduction potentials, and UV-visible and ESR spectra of the covalent complex were consistent with the composition cyt/pc and with a lack of noticeable structural perturbations of the protein molecules. Isoelectric focusing showed the presence of N-acylurea groups, byproducts of the cross-linking reaction [Zhou, J.S., Brothers, H.M. II, Neddersen, J.P., Peerey, L.M., Cotton, T.M., & Kostic, N.M. (1992) Bioconjugate Chem. 3, 382]. Laser flash spectroscopy, with riboflavin semiquinone as the reductant, showed that the electrontransfer reaction within the covalent complex cyt(II)/pc(II) is either undetectably slow or reversible. The question was resolved by monitoring, during redox titrations, the 1H NMR line widths of the heme methyl groups in free ferricytochrome f and in this protein cross-linked to plastocyanin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507643 TI - Cation binding and conformation of human calmodulin-like protein. AB - The Ca(2+)-binding parameters of recombinant human calmodulin-like protein (CLP), a protein specifically expressed in mammary epithelial cells, were studied by flow dialysis in the absence and presence of 2, 10, and 30 mM MgCl2. In general, the four intrinsic binding constants (K'Ca) are about 8-fold lower than in animal and plant calmodulins. In the absence of Mg2+ the K'Ca values of the four binding steps equal 4.0 x 10(3), 3.3 x 10(4), 1.0 x 10(4), and 6.0 x 10(3) M-1, respectively. They allow us to distinguish two pairs of sites: a higher affinity pair with strong positive cooperativity and a lower affinity pair composed of non interacting sites with different affinities. Mg2+ antagonizes Ca2+ binding by decreasing only Ca(2+)-binding steps 2 and 3, so that at high Mg2+ concentrations the positive cooperativity in the high-affinity pair has been lost and that the four K'Ca values are very similar with a mean K'Ca of 4 x 10(3) M-1. Direct Mg2+ binding studies by equilibrium gel filtration indicate that 4-5 Mg2+ bind to CLP with a mean K'Mg of 250 M-1. Conformational changes in the unique Tyr138 microenvironment, monitored by fluorimetry and near-UV difference spectrophotometry, indicate that in metal-free CLP this Tyr is shielded from the polar solvent and strongly quenched by a specific chemical group; Ca2+ binding induces a shift of Tyr to a more polar environment and removal of the quenching group, but without full exposure to the solvent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8507644 TI - Secondary structure of the particle associating domain of apolipoprotein B-100 in low-density lipoprotein by attenuated total reflection infrared spectroscopy. AB - The secondary structure of the human low-density lipoprotein (LDL) apo B-100 fragment embedded in the lipid domain of the particle has been investigated by Fourier transform attenuated total reflection infrared spectroscopy (FTIR-ATR). The solvent-exposed region of the protein was hydrolyzed by using different proteases (alpha-chymotrypsin, trypsin, proteinase K) for incubation times varying between 24 min and 48 h. Analysis of the FTIR-ATR spectra after repurification of the digested LDL particle indicates the same trend for all the hydrolysis conditions tested: the peptides remaining associated with the particle are rich in beta-sheet structure. Dichroism spectra reveal that at least part of the beta-sheets is associated with the phospholipid component of the particle. PMID- 8507645 TI - Mammalian passive glucose transporters: members of an ubiquitous family of active and passive transport proteins. PMID- 8507646 TI - Cell electropermeabilization: a new tool for biochemical and pharmacological studies. AB - Cell electropermeabilization is the transient permeabilization of the plasma membrane by means of short and intense electric pulses. Under optimized conditions, electropermeabilization is compatible with cell survival. It provides a direct access into the cytosol to ions, small molecules, exogenous drugs and macromolecules. As cells remain functional, a large variety of cell biology questions can be addressed. Such 'in situ biochemistry' opens new possibilities beside the more classical studies dealing with unpermeabilized cells or subcellular extracts. Electropermeabilization also allows pharmacological studies with cells, cultured monolayers and in vivo tissues as well as the design of drug controlled-release systems. PMID- 8507647 TI - Iodide transport in the thyroid gland. PMID- 8507649 TI - Three-dimensional electric field traps for manipulation of cells--calculation and experimental verification. AB - The forces acting on dielectric particles and living cells exposed to alternating and rotating fields generated by three-dimensional multi-electrode arrangements are investigated. Numerical procedures are described for the calculation of the electric field distribution and forces. The physical treatment considers electrodes of any shape and dielectric particles of complex structure. Particle and cell trapping are based on negative dielectrophoretic forces produced by high frequency a.c. or rotating electric fields up to 400 MHz. Various multi-electrode systems were realised in commercially fabricated microelectrode systems, and tested for their ability to move and assemble microparticles or living cells without contact with the electrodes. The field distribution and accuracy of phase controlled power application was tested using individual artificial particles trapped in the electric field cage. Position and trajectories of particle motion were measured. The paper gives an overview of electrode and field cage design in the microscale range. PMID- 8507648 TI - Role of Hageman factor/kallikrein-kinin system in pseudomonal elastase-induced shock model. AB - The role of the Hageman factor dependent pathway in pseudomonal elastase-induced shock was investigated in guinea pigs. Presence of a bradykinin B2 receptor antagonist [D-Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin (200 nM) in the circulation prevented shock caused by an intrajugular injection of pseudomonal elastase (0.8 mg/kg body weight). During the lethal shock caused by elastase (1.2 mg/kg), a significant consumption of components of the Hageman factor/kallikrein-kinin system was observed such as 45.7 +/- 2.20% consumption of Hageman factor, 100 +/- 0% of prekallikrein, and 85.1 +/- 2.50 of high-molecular-weight kininogen. More striking evidence for the participation of this system was demonstrated in depletion experiments with monospecific F(ab')2 antibodies against the components of the system. After depletion of any one of the components, guinea pigs exhibited unresponsiveness to the same lethal dose of pseudomonal elastase in regard to the cardio-respiratory alterations. In vitro, pseudomonal elastase (60 micrograms/ml) possessed a capacity to generate substantial amount of bradykinin in undiluted plasmas of humans (300.0 +/- 32.16 ng/ml) as well as guinea pigs (460.2 +/- 20.67 ng/ml) at 37 degrees C but not in those deficient in Hageman factor or prekallikrein. These results strongly suggested a pathological role of elastase in pseudomonal sepsis through activation of the Hageman factor dependent pathway. PMID- 8507650 TI - A new mixed disulfide species in human cataractous and aged lenses. AB - The process of ageing in the normal human eye lens is unique among tissues due to the absence of turnover in the structural proteins. These proteins accumulate a variety of modifications throughout their lifetime. Significantly, the cysteine residues are subject to disulfide formation with the low molecular weight thiol compounds present in the lens. It has been shown that accumulation of glutathione and cysteine mixed disulfides in the proteins of normal human lens is a function of age. In this report a third mixed disulfide species gamma-glutamylcysteine (gamma-Glu-Cys), has been identified by comparison with standards which were produced through two distinct methods. This new mixed disulfide is only prominent in old lenses (> 60 years) and cataractous lenses. In these situations its level may approach those of cysteine mixed disulfide. The appearance of gamma-Glu-Cys may be coincident with biochemical abnormalities preceding cataract formation. This protein modification may be a result of changes in the GSH biosynthetic pathway within the lens. PMID- 8507651 TI - Hydrogen peroxide metabolism and oxidative stress in cortical, medullary and papillary zones of rat kidney. AB - The cortical, medullary and papillary regions of rat kidney were evaluated for a series of parameters related to hydrogen peroxide metabolism and oxidative stress. The rates of oxygen uptake, prostaglandin synthesis and malondialdehyde production by kidney slices were: 47, 0.003 and 0.051 mumol/h g wet wt., respectively, in cortex, 32, 0.023 and 0.035 in medulla and 22, 0.034 and 0.007 in papilla. The activities of superoxide dismutase, catalase and glutathione peroxidase were: 144 +/- 16 U/g wet wt., 880 +/- 100 pmol/g wet wt. and 177 +/- 16 U/g wet wt. in cortex; 97 +/- 9 U/g wet wt., 550 +/- 50 pmol/g wet wt. and 142 +/- 18 U/g wet wt. in medulla; and 23 +/- 2 U/g wet wt., 90 +/- 9 pmol/g wet wt. and 147 +/- 5 U/g wet wt. in papilla. Hydrogen peroxide steady-state concentrations were 0.09 +/- 0.01, 0.07 +/- 0.01 and 0.08 +/- 0.01 microM whereas alpha-tocopherol content was 21 +/- 2, 23 +/- 1 and 34 +/- 3 mumol/g wet wt. and hydroperoxide-initiated chemiluminescence was 22 +/- 2, 33 +/- 2 and 14 +/- 1 cpm. 10(-3)/mg prot for cortex, medulla and papilla, respectively. After 60 min ischemia-30 min reperfusion hydroperoxide-initiated chemiluminescence and hydrogen peroxide steady-state concentration increased by 30% and 60% in cortex and 80% and 60% in medulla, whereas alpha-tocopherol content decreased by 30%, 50% and 2% in cortex, medulla and papilla, respectively. The reperfusion/control ratio of hydroperoxide-initiated chemiluminescence and hydrogen peroxide steady state concentrations in cortex and medulla indicate the occurrence of oxidative stress after ischemia-reperfusion. The lower sensitivity to oxidative stress found in papilla could be explained by the relatively high relationship of alpha tocopherol content to hydrogen peroxide production rate in this sub-organ. PMID- 8507652 TI - Identification and characterization of two enzymes involved in the intracellular metabolism of cobalamin. Cyanocobalamin beta-ligand transferase and microsomal cob(III)alamin reductase. AB - Two enzymes involved in the intracellular metabolism of cobalamin have been identified and characterized: cyanocobalamin beta-ligand transferase and microsomal cob(III)alamin reductase. The beta-ligand transferase is a cytosolic enzyme utilizing FAD, NADPH and reduced glutathione. The product of the reaction has been identified as glutathionyl-cobalamin. NADH-linked cob(III)alamin reductase has been found in two subcellular fractions: microsomal and inner mitochondrial membrane. The product of the reduction catalyzed by the microsomal enzyme has been identified as cob(II)alamin. In cbl C mutant fibroblasts, the specific activities of cyanocobalamin beta-ligand transferase and cob(III)alamin reductase were markedly decreased and have varied from 3%-30% and 36%-42% of normal, respectively. The specific activity of mitochondrial cob(III)alamin reductase was only 30% of normal in two cbl C mutants and normal in remaining mutant cell lines. In the cbl D cells, the specific activities were 33% and 55%. Mitochondrial cob(III)alamin reductase was not affected by cbl D mutation. Methionine synthase, L-methylmalonyl-CoA mutase and microsomal cytochrome c and b5 reductases are not affected by both mutations. The cbl E mutation affects only the activity of methionine synthase. These results support the hypothesis that the early enzymatic steps of intracellular metabolism of cobalamin are similar in the synthesis of both methylcobalamin and adenosylcobalamin and these steps are altered by the cbl C and cbl D mutations. PMID- 8507653 TI - Purification and characterization of the valine sensitive acetolactate synthase from Serratia marcescens ATCC 25419. AB - The valine sensitive acetolactate synthase (ALS) isozyme from Serratia marcescens ATCC 25419 was purified to homogeneity. Analysis of the native molecular weight of the purified enzyme by the native pore gradient polyacrylamide gel electrophoresis indicated the molecular weight of about 178,000 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the enzyme to be composed of two different types of subunits with molecular weights of 62,000 and 35,000. The molar ratio of the two polypeptides was estimated to be 1, suggesting that native enzyme is composed of two large subunits and two small subunits. The enzyme exhibits homotropic allosterism with pyruvate unlike other enteric ALS isozymes. The specificity ratio R (V[acetohydroxybutyrate]/V[acetolactate] = R.[alpha-ketobutyrate]/pyruvate]), of the enzyme was found to be 0 suggesting that the Serratia ALS has very high specificity for pyruvate. The pH optimum was around 7.5, and the enzyme was stable at 50 degrees C for 30 min. The pI value for the purified enzyme was 5.2. The concentration of branched chain amino acids for 50% inhibition of the enzyme was 0.1 mM for valine, and 1 mM for leucine and isoleucine, respectively. PMID- 8507654 TI - Polymorphic hemoglobin from a midge larva (Tokunagayusurika akamusi) can be divided into two different types. AB - The hemoglobin from the 4th-instar larva of Tokunagayusurika akamusi, a common midge found in eutrophic lakes in Japan, was composed of as many as 11 separable components (IA, IB, II, III, IV, V, VIA, VIB, VII, VIII, IX) on a DEAE-cellulose column. However, we have found that these components can be divided into two groups on the basis of their spectroscopic properties, one being named as the normal type (N-type) and the other being referred to as the low type (L-type). Since the major difference between them seemed to be the presence or absence of the distal (E7) histidine residue, which plays an important role in the stability properties of the bound dioxygen, the complete amino acid sequence was then determined for each typical component, namely, VII (N-type) and V (L-type): the former hemoglobin contained the usual distal histidine residue at position 64, whereas the latter one replaced it by isoleucine at position 66. The homology test for 40 N-terminal amino acid residues of all components also demonstrates that T. akamusi hemoglobin is composed of two different clusters showing a very early separation in the phylogenetic tree. PMID- 8507655 TI - Preparation and characterization of S-[2-carboxy-1-(1H-imidazol-4 yl)ethyl]glutathione and its derivatives as proposed precursors of S-[2-carboxy-1 (1H-imidazol-4-yl)ethyl]cysteine, a compound found in human urine. AB - Formation of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid (I) and S [2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (II), compounds found in human urine, has been demonstrated by enzymatic degradation of S-[2-carboxy-1-(1H imidazol-4-yl)ethyl]glutathione (III). Compound (III) was chemically synthesized in 72% yield by incubating the reaction mixture of trans-urocanic acid and 3-fold excess GSH at 65 degrees C for 1 wk, which was accompanied by formation of N-(S [2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteinyl)glycine (IV) in 15% yield. S-[2 Carboxy-1-(1H-imidazol-4-yl)ethyl]-N-gamma-glutamylcysteine (V) was produced by partial hydrolysis of compound (III) in HCl. The synthesized compounds were characterized mainly by fast-atom bombardment mass spectrometry and high-voltage paper electrophoresis as well as chemical degradation. Incubation of compound (III) with rat kidney homogenate in a Tris buffer (pH 8), formed compound (II) in 80% yield possibly via compound (IV). Yield of compound (II) was increased by adding glycylglycine to the reaction mixture. However, little degradation of compound (III) occurred in the use of rat liver, brain, heart or spleen homogenate as the enzyme source. Compound (II) was further metabolized to compound (I) by incubation with rat kidney homogenate in a phosphate buffer of pH 7.4. From these results, we suggest that the urinary compounds are products of enzymatic degradation of compound (III) and that GSH may participate in the metabolism of urocanic acid, the first catabolite of L-histidine. PMID- 8507656 TI - Localisation of alpha, mu and pi class glutathione S-transferases in kidney: comparison with CuZn superoxide dismutase. AB - We describe studies in whole kidney, cortical and medullary homogenates and, glomerular cells in culture to determine the relative levels of expression of alpha (Ya, Yc, Yk), mu (Yb1/Yb2), pi (Yf) glutathione S-transferases (GST) and CuZn superoxide dismutase (CuZn SOD) in different regions of the nephron. Immunoblotting and immunohistochemistry were used to demonstrate relatively weak expression of alpha, mu GST and, CuZn SOD in the glomerulus compared to that in particularly distal tubules. Whilst expression of Ya was found within glomerular cells, Yc, Yk and Yf were not detected. Immunofluorescence showed that Ya and Yb1/Yb2 but not Yf were expressed in cultured epithelial and mesangial cells studied between passages 1 and 3. While Ya was distributed in cytosol, Yb1/Yb2 was primarily located in nuclei. PMID- 8507657 TI - On the inactivation of bacteria by singlet oxygen--another view. AB - Midden and Dahl, in a recent paper, have presented important data on the inactivation of bacteria by singlet oxygen. In analyzing the data, use was made of a theory published earlier by the present author. The purpose of this paper is to point out that theory and experiment can be brought into better agreement by assuming that the interaction of singlet oxygen with the bacteria takes place in an essentially lipid environment rather than aqueous. PMID- 8507658 TI - Solvent effect on testosterone-antitestosterone interaction. AB - The inhibition of the binding between testosterone and antitestosterone antiserum caused by organic solvents was studied at pH 7.4, 298 K. Inhibition curves were obtained at variable ranges of molar fractions for the following solvents: methanol (range 0-0.4), ethanol (0-0.317), 1-propanol (0-0.082), 2-propan-ol (0 0.260), t-butanol (0-0.223), ethylenglycol (0-0.189), 2-methoxyethanol (0.036), 2 butoxyethanol (0-0.063), 1,4-dioxan (0-0.124), tetrahydrofuran (0-0.238) and acetonitrile (0-0.392). Steroid-antibody binding decreases with increasing molar fraction of solvent in the reaction mixture for all but tetrahydrofuran and acetonitrile, which enhance binding at low molar fraction then cause a sharp inhibition. Molar fraction of solvent that causes a 50% binding inhibition is uncorrelated to some solvent properties (i.e. dielectric constant, polarity index, dipole moment) but is inversely correlated to the molecular mass of the solvent. The correlation becomes better by taking into account the length of the solvent molecule, or the Randic molecular connectivity index, suggesting that binding inhibition could be related to the length of the solvent molecules that displace water around the steroid molecule. However, the increase of binding observed at low molar fraction with tetrahydrofuran and acetonitrile, together with very different shapes of inhibition curves suggest that a molecular mechanism based on the differential solvation of the steroid by solvent and water molecules must be taken into account to explain adequately the solvent effect on testosterone-antitestosterone interaction. PMID- 8507659 TI - Further characterization of an adenosine-containing modification of vaccinia virus proteins. AB - Three vaccinia virus (VV) core proteins which become labeled when virus is grown in the presence of radiolabeled adenosine or orthophosphate were identified as the major viral core proteins 4A, 4B, and 25K on the basis of comigration with [35S]methionine-labeled viral proteins and immunoprecipitation with monospecific polyclonal antisera. Boronate affinity chromatography and HPLC analysis suggested that a cis-diol-containing adenosine compound is present on this set of viral proteins. The replication of VV in tissue culture cells was prevented by the ADP ribosylation inhibitors nicotinamide (NIC), 3-aminobenzamide (3-AB), and meta iodobenzylguanidine (MIBG). None of these compounds significantly affected viral DNA synthesis at lower drug concentrations, although at higher concentrations of the three drugs a reduction in viral DNA synthesis was evident. Total VV protein synthesis also decreased at higher inhibitor levels, and the proteolytic processing of the major virion core proteins was greatly diminished as well. The three inhibitors also affected labeling of viral core proteins and cellular histone proteins by [8-14C]adenosine. In addition, mature, infectious virus particles were not formed in the presence of either 60 mM NIC or 3-AB, or 0.6 mM MIBG. These results provide evidence that the major VV core proteins are subject to modification by an adenosine compound, and suggest the possibility that this modification might represent ADP-ribosylation. PMID- 8507660 TI - Photoreversible change in the conformation of phytochrome as probed with a covalently bound fluorescent sulfhydryl reagent, N-(9-acridinyl)maleimide. AB - A fluorescent SH reagent, N-(9-acridinyl)maleimide (NAM), was used as a fluorescent probe to detect changes in the conformation of phytochrome from pea (Pisum sativum) seedlings during photoconversion between the red-light absorbing form (Pr) and the far-red-light absorbing form (Pfr). NAM-Cys conjugates emitted weaker fluorescence in non-polar solvent than in polar solvent. The fluorescence intensity (FI) of NAM-phytochrome conjugates depended on the absorbing form of phytochrome: the FI of NAM-Pr was greater than that of NAM-Pfr, indicating that the Cys residues modified by NAM were in more hydrophobic environment in Pfr than in Pr. The FI of the conjugate prepared from a red-light-irradiated sample of phytochrome was greater than that for the conjugate prepared from Pr, indicating that more Cys residues were modifiable in Pfr than Pr. The fluorescence polarization of the conjugate (0.0251) indicates that the modified Cys residues may be located at the surface of the phytochrome molecule. The FI of phytochrome conjugates with 8-anilinonaphthalene-1-sulfonate (ANS) did not change with the photoconversion of phytochrome. The FI of a mixture of ANS and phytochrome increased upon the first photoconversion of Pr to Pfr. However, it did not change upon subsequent photoconversion between Pr and Pfr. These results suggest that the initial increase in FI may have resulted from the binding of additional ANS to Pfr and that the microenvironment of bound ANS may not be influenced by the photoconversion of phytochrome. PMID- 8507661 TI - Purification and molecular cloning of mouse renal dipeptidase. AB - Mouse renal dipeptidase (mouseRDP, EC 3.4.13.11) was purified from the membrane fraction of kidney. The molecular mass of the enzyme was 115 kDa by size exclusion HPLC and SDS-PAGE under non-reduced conditions and 58 kDa by SDS-PAGE under reduced conditions. The mouseRDP cDNA fragment was amplified from mouse kidney total RNA by reverse transcription-polymerase offin reaction (RT-PCR). The mouseRDP cDNA was isolated from a kidney cDNA library using the probe. The primary structure of mouseRDP deduced from the cDNA showed a high homology with renal dipeptidase from various mammals, except for the amino-terminal and carboxy terminal domains. Recombinant mouseRDP obtained from transfected mouse L929 cells containing the expression plasmids has the same Km value and molecular mass as native mouse renal dipeptidase. From Northern blotting analysis, expression of the mouseRDP gene was recognized in both kidney and liver. PMID- 8507662 TI - Pro-major basic protein has three types of sugar chains at the pro-portion. AB - The amino-acid sequence of purified recombinant pro-major basic protein from Chinese hamster kidney cells was determined to verify the primary structure and glycosylation sites. Reduced and S-carboxamidemethylated protein was first digested with Achromobacter proteinase I. Each peptide was characterized by amino acid analysis and amino-acid sequence analysis. We could identify all the peptides which were expected from the pro-major basic protein cDNA sequence. Sequence analysis and deglycosylation study revealed that Ser-8, Thr-9, Ser-46 and Asn-70 were glycosylated. The results indicated that proMBP has three types of sugar chains, O-glycoside, N-glycoside and glycosaminoglycan, in the pro portion. PMID- 8507663 TI - Physical characterization of recombinant tissue plasminogen activator. AB - Electron microscopic and physical-chemical properties of one- and two-chain tissue plasminogen activator (t-PA) were studied. The molecular weight of one chain t-PA obtained by both sedimentation equilibrium and SDS-PAGE was estimated to be about 65,000, while both chains in the reduced two-chain form were in the range of 35,000-40,000. Sedimentation coefficients were identical for both forms of t-PA (S(0)20,w = 4.12). The two forms of t-PA were indistinguishable by electron microscopic analysis, which confirmed the sedimentation results, and showed that they were ellipsoidal and relatively compact. The major and minor axes were approx. 13 nm and approx. 10 nm and f/f0 was 1.36. The individual domains of t-PA are relatively small and are folded within the molecule, so that the overall appearance is globular. PMID- 8507664 TI - The anaerobic reaction of bovine hemoglobin with divinyl sulfone: structural changes and functional consequences. AB - The anaerobic reaction of bovine hemoglobin with divinyl sulfone results in a non cross-linked intramolecularly-modified new derivative. This chemically-modified hemoglobin is homogeneous with respect to its molecular mass (64 kDa) and electrophoretic properties. The absence of any 32 kDa band from its SDS-PAGE pattern proves the lack of intramolecular cross-linkage, while a single-peak high performance gel-permeation chromatogram demonstrates the absence of intermolecular cross-linkage. The oxygen binding properties determined at 37 degrees C, 0.15 M Cl- and pH 7.4 display a P50 of 52 mmHg and a Hill coefficient n of 1.9. Under the same experimental conditions the oxygen affinity is not sensitive to chloride anions, suggesting that the covelant modification is in the beta-cleft. The maximum number of Bohr protons released is 0.8/tetramer, which is half that of normal bovine hemoglobin. The retention time in circulation, measured in rats, is similar to that of native bovine hemoglobin. Using a high molar ratio of divinyl sulfone to modified hemoglobin, it is feasible to effect anaerobic intermolecular cross-linkage. The polymerized material, isolated from a 24 h reaction, is a mixture of modified intermolecularly-crosslinked hemoglobins with a molecular mass range from 130 to approx. 500 kDa. The oxygen-transport characteristics of the polymerized material are similar to those of the modified non-cross-linked derivative, whereas its retention time in rats is increased three-fold with respect to native bovine hemoglobin. PMID- 8507665 TI - Glutathione S-transferases of human skin: qualitative and quantitative differences in men and women. AB - Glutathione S-transferase (GST) isozymes of male and female leg skin have been characterized. GST activities and protein have been quantified in a number of male and female skin samples and the results indicate that as compared to the male skin, female skin contains a higher amount of GST activity as well as protein. Both male and female leg skin contain three GST isozymes with pI values 9.9, 9.1 and 4.8. In accordance with previous findings the major isozyme, pI 4.8 belongs to the pi-class, whereas the two minor forms pI 9.1 and 9.9 belong to the alpha-class. Each of the three isozymes is more abundant in female skin. Surprisingly, the specific activities and Kcat values of the female skin GSTs, particularly of the pi-class isozyme were found to be significantly higher as compared to those of male skin isozyme. Studies into the kinetics of inhibition by hematin also indicated differences in male and female skin GSTs. Whereas we confirm the presence of an alpha-class GST, pI 9.9, in human skin with an apparently higher subunit M(r) value as compared to other human alpha-class GSTs, contrary to the previous report (Del Boccio et al. (1987) Biochem. J. 244, 21 25), the results of the present studies show that the N-terminus of this alpha class GST is blocked. PMID- 8507666 TI - Inactivation of histidine ammonia-lyase from Streptomyces griseus by dicarbonyl reagents. AB - Histidine ammonia-lyase from Streptomyces griseus was inactivated by methylglyoxal and phenylglyoxal, dicarbonyl reagents known to react specifically with arginyl residues in proteins. The inactivation showed pseudo-first-order kinetics and could be prevented by protection with histidinol phosphate, a competitive inhibitor of histidine ammonia-lyase. Analysis of the amino acid composition of histidine ammonia-lyase after treatment with phenylglyoxal, together with the kinetics of inactivation, suggested that inactivation was a consequence of specific reaction with one or more essential arginyl residues at or near the active site of the enzyme. PMID- 8507668 TI - NMR study of the molecular and electronic structure of the heme cavity in Dolabella met-cyano myoglobin. AB - The molecular and electronic structure of the active site of the cyanide-ligated ferric complex of the myoglobin from the mollusc Dolabella auricularia has been investigated using NMR. Analysis of nuclear Overhauser effects has revealed that the correlation times for the internal motion of the heme propionate alpha-CH2 and beta-CH2 groups at ambient temperature are about 5 and 4 ns, respectively. These correlation times indicate that the terminal carboxylate groups of both the heme propionates are not bound to the protein via salt bridges. Although the absence of the propionate-protein interaction does not influence the equilibrium population of the two heme orientational isomers involving rotation about the alpha,gamma-meso axis, it allows the heme to rotate about the iron-His bond in the active site of the myoglobin. Such rotational motion of the heme resulted in an anomalous temperature-dependence of the heme methyl-proton hyperfine shift. Thus the present myoglobin studies provide the first example demonstrating the rotation of the heme about the iron-His bond in native myoglobin. PMID- 8507667 TI - The effect of Ca2+ on the conformation of tropomyosin and actin in regulated actin filaments with or without bound myosin subfragment 1. AB - The effects of Ca2+ and myosin subfragment 1 on the conformation of tropomyosin and actin in regulated actin filaments in ghost fibers were investigated by means of the polarized fluorescence technique. Regulated thin filaments were reconstituted in skeletal muscle ghost fibers by incorporation into the fibers of either skeletal muscle troponin-tropomyosin or smooth-muscle caldesmon-calmodulin tropomyosin complexes. Tropomyosin and actin were specifically labeled with fluorescent probes, 1,5-IAEDANS and phalloidin-rhodamine, respectively. Analysis of the fluorescence parameters indicated that the binding of Ca2+ to regulated actin filaments induces conformational changes in tropomyosin and actin that lead to the strengthening of the interaction between these two proteins and weakening of the binding of actin monomers in the filament. These changes become larger when regulated actin forms rigor links with myosin subfragment 1. No notable alterations in the position of tropomyosin relative to actin in the frontal plane of the fiber were detected either upon binding of Ca2+ or upon the additional binding of myosin subfragment 1 to regulated actin. PMID- 8507669 TI - Effect of ferrous ions on the monophenolase activity of tyrosinase. AB - The effect of ferrous ions on the monophenolase activity of tyrosinase has been studied. Although a shortening of the lag period which characterizes this hydroxylation reaction was observed, no direct effect on the enzyme was found. The reaction between ferrous ions and molecular oxygen in the presence of chelating agents, such as phosphate or EDTA, produces hydroxyl radicals. These radicals can hydroxylate tyrosine to generate L-3,4-dihydroxyphenylalanine (dopa). Catalase and scavengers of hydroxyl radicals inhibited both the shortening of the lag period and dopa formation. On the basis of these results, it is proposed that the influence of ferrous ions on tyrosinase is due to the formation of dopa in the chemical hydroxylation of tyrosine. Dopa transforms the Emet form of the enzyme (Cu2+Cu2+) into the Edeoxy form (Cu1+Cu1+) and, thus, shortens the lag period. PMID- 8507670 TI - An asynchronous unfolding among molecular different regions of lobster D glyceraldehyde-3-phosphate dehydrogenase and maltotetraose-forming amylase from an Alcaligenes sp. during guanidine denaturation. AB - Changes in ultraviolet absorbance and intrinsic protein fluorescence of 1,4-alpha D-glucan maltotetrahydrolase (EC 3.2.1.60) from an Alcaligenes sp. (Gram-negative bacteria 537.1) and D-glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) have been compared with their inactivation during denaturation in guanidinium-Cl solutions. The two enzymes were completely inactivated at GuHCl concentrations less than 0.6 M and this was accompanied by marked absorbance and intrinsic fluorescence changes suggesting exposure of aromatic residues. The changes of the intrinsic fluorescence of the amylase have a relatively constant plateau in emission intensities and maxima at GuHCl concentrations from 0.8-2.0 M, similar to that of muscle GAPDH. The relative activity of the enzyme increased markedly in dilute GuHCl solutions accompanied by very little change of its intrinsic fluorescence at 8 degrees C. The kinetic decrease in emission intensities, excited respectively by 230 nm and 292 nm, was different for the two enzymes. The inactivation was a biphasic process with a fast phase faster than the unfolding rate as measured by fluorescence changes in 0.5 M GuHCl solution. Similar to the inactivation process, changes in intensity of 410 nm NAD fluorescent derivative of GAPDH which is in situ at the active site is also a biphasic process under the same condition. It appears that there may be an unfolding intermediate state of the enzymes and an asynchronous unfolding process among the different regions in the molecules during GuHCl denaturation, this may be due to differences in their flexibility. PMID- 8507671 TI - NMR studies of the alpha-chymotrypsin-(R)-1-acetamido-2-(4- fluorophenyl)ethane-1 boronic acid complex. AB - The interaction of (R)-1-acetamido-2-(4-fluorophenyl)ethane-1-boronic acid with alpha-chymotrypsin at pH 4 was studied by a variety of 19F-NMR experiments. It was demonstrated that this compound forms a complex with a 1:1 stoichiometry, probably because the boronic acid acts as a 'transition state' inhibitor of the enzyme. Analysis of fluorine T1 relaxation behavior and 19F[1H] NOE data shows that the rate constant for dissociation of the complex is 1.3 s-1 and that the motion of the 4-fluoroaromatic ring within the complex can be characterized by an overall rotational correlation time of 13 ns and a correlation time for rotation about its local C2 axis of 110 ns. Enzyme-induced fluorine chemical shifts, fluorine relaxation times, line width data and 2D 19F[1H] NOE results suggest that the structure of the complex in the vicinity of the fluoroaromatic ring is similar to that found in a closely similar acylated enzyme. However, the dynamics of 4-fluoroaromatic ring motions are different in the two systems, with the ring being slightly more mobile in the boronic acid complex than in the acylenzyme. PMID- 8507672 TI - Characterization of linear and cyclic glucagon analogs by fast atom bombardment mass spectrometry. AB - Fast atom bombardment mass spectral mapping of endoproteinase Asp-N digest mixtures is used for characterization of new synthetic linear and cyclic glucagon analogs. The results allow rapid identification of sequence modifications in linear glucagon analogs. For the cyclic compounds, the technique allows confirmation of the presence and position of the cyclic amide bond, as well as verification of the sequence of the modified glucagon analogs. The specificity of the Asp-N enables differentiation of isometric glucagon analogs which differ only in the position of the cyclic amide bond. Important information concerning the purity of the synthetic analogs is also available. PMID- 8507673 TI - Fast atom bombardment mass spectrometry of sucrose monocaprate and sucrose monolaurate. AB - Fast Atom Bombardment (FAB) ionization of sucrose monocaprate and sucrose monolaurate in the presence of Na+ ions shows the formation of both [M+Na]+ and [M - H]- ions. The [M+Na]+ ions undergo charge-remote fragmentations when collisionally activated at high translational energy. These charge-remote fragmentations are useful for the structural determination of the acyclic part of the glycolipid. In the negative ion mode both sucrose esters yield anions which can be attributed to the saccharide and lipid components of these glycolipids. Structural characterization of the fatty acid can be achieved as the released carboxylate anions undergo charge-remote fragmentations that are consistent with the ion chemistry of [M - H]- anions from FAB-ionized free fatty acids. PMID- 8507675 TI - Journey to the light: ASDA member describes dental mission to West Africa. PMID- 8507674 TI - Structural analysis of hydroxy fatty acids by thermospray liquid chromatography/tandem mass spectrometry. AB - Thermospray liquid chromatography/tandem mass spectrometry provides a sensitive and convenient technique for the structural analysis of oxygenated polyunsaturates. Analysis of pentafluorobenzyl derivatives in the negative ion mode under the filament- or discharge-on condition generated abundant [M - PFB]- ions. These ions were further fragmented by collision with argon and detected in the negative ion mode. The negative ion fragmentation pattern was examined for various oxygenated polyunsaturated fatty acid standards as well as their deuterated and/or hydrogenated forms. Characteristic fragmentation occurs at the oxygenated C-C bonds, allowing unambiguous determination of the sites of oxygenation. The sample amount required is typically in the low tens of nanogram range. Using this method the structures of epoxy, hydroxy derivatives of 4,7,10,13,16,19-docosahexaenoic acid (22:6w3) formed by soybean lipoxygenase were determined. They were 13-hydroxy-16,17-epoxy-22:5w3 and 15-hydroxy-16,17-epoxy 22:5w3. PMID- 8507676 TI - Metabolic pathways in mammalian peroxisomes. AB - This article summarizes our current knowledge of the metabolic pathways present in mammalian peroxisomes. Emphasis is placed on those aspects that are not covered by other articles in this issue: peroxisomal enzyme content and topology; the peroxisomal beta-oxidation system; substrates of peroxisomal beta-oxidation such as very-long-chain fatty acids, branched fatty acids, dicarboxylic fatty acids, prostaglandins and xenobiotics; the role of peroxisomes in the metabolism of purines, polyamines, amino acids, glyoxylate and reactive oxygen products such as hydrogen peroxide, superoxide anions and epoxides. PMID- 8507677 TI - Peroxisomal oxidation of the steroid side chain in bile acid formation. AB - An overview of the formation of the primary bile acids is given with special emphasis on the final steps, ie the oxidative cleavage of the steroid side chain. The enzymes involved in this oxidation are localized to liver peroxisomes and catalyze conversion of di- and trihydroxy-5 beta-cholestanoic acid into chenodeoxycholic and cholic acid, respectively. Two of the intermediates in cholic acid formation have been identified, viz 3 alpha, 7 alpha, 12 alpha trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha, 7 alpha, 12 alpha, 24 tetrahydroxy-5 beta-cholestanoic acid. The corresponding hypothetical 24-oxo compound has not been finally identified. The first enzyme in the reaction sequence, trihydroxy-5 beta-cholestanoyl-CoA oxidase, has recently been partly purified and shown to be separate from the corresponding peroxisomal acyl-CoA oxidase. The subsequent enzymes, the trifunctional enzyme and the thiolase, are most certainly shared in the oxidation of both fatty acids and cholestanoic acids. In several peroxisomal disorders bile acid intermediates with an uncleaved steroid side chain accumulate, thus clearly demonstrating the importance of liver peroxisomes in the normal formation of bile acids in man. PMID- 8507678 TI - Biosynthesis of dolichol and cholesterol in rat liver peroxisomes. AB - Isolated rat liver peroxisomes contain the complete enzymatic machinery required for the synthesis of both cholesterol and dolichol from farnesyl pyrophosphate. Additionally, the whole or part of the initial portion of the mevalonate pathway between acetyl-CoA and farnesyl pyrophosphate is also present in peroxisomes. Cholesterol and dolichol biosynthesis in peroxisomes is more complete than in ER since peroxisomes contain high concentrations of sterol carrier protein-2, a protein that stimulates both dolichol and cholesterol biosynthesis. Approximately 50 and 20% of the total hepatic dolichol and cholesterol biosynthesis is associated with rat liver peroxisomes, respectively. Upon dietary and drug treatments the synthesis of these lipids displays different regulation in peroxisomes and ER. PMID- 8507679 TI - Peroxisomal beta-oxidation of polyunsaturated fatty acids. AB - Peroxisomes have been shown to play an important role in the oxidative degradation of (poly)unsaturated fatty acids, and contain the enzyme activities needed for the metabolism of double bonds of unsaturated fatty acids in connection with this physiological function. Our understanding of the metabolic pathways and enzyme activities involved in the degradation of unsaturated acyl CoAs has undergone a re-evaluation recently, and though many open questions still remain significant progress has been made, especially concerning the reactions metabolizing double bonds. The enzyme activities to be discussed here are 2,4 dienoyl-CoA reductase; 3/2-enoyl-CoA isomerase; 2-enoyl-CoA hydratase 2; 5-enoyl CoA reductase and 3,5/2,4-dienoyl-CoA isomerase. Some of these activities are integral parts of the multifunctional proteins of beta-oxidation systems, which must also be taken into account in this context. PMID- 8507680 TI - Ether lipid synthesis and its deficiency in peroxisomal disorders. AB - This paper deals with the discovery of plasmalogen deficiency in the cerebro hepato-renal (Zellweger) syndrome and discusses how this has led to the development of postnatal and prenatal diagnostic procedures for this and a number of related peroxisomal disorders in man that show a general impairment in the biosynthesis of ether glycerophospholipids. The results have clearly shown an indispensable role for peroxisomes in the total process of ether lipid synthesis as evidenced by a description of the cellular topography of this process. Platelet-activating factor is a bioactive phospholipid in which the glycero-ether linkage is essential for its biological activities. The deficient formation of this lipid mediator can be correlated to the residual amounts of ether phospholipids found in patients with impaired ether lipid production. Evidence is provided to demonstrate that the extent to which cells upon stimulation produce platelet-activating factor and its 1-acyl counterpart is not caused by enzyme selectivities for ether-linked versus ester-linked phospholipid species. Rather, the relative production of these compounds appears to be mainly governed by the relative abundance of ether-linked and ester-linked precursor molecules and the activity of cellular enzymes, such as lysophospholipases, that catabolize the acyl analog of platelet-activating factor through deacylation. PMID- 8507681 TI - The non-specific lipid-transfer protein (sterol carrier protein 2) and its relationship to peroxisomes. AB - The non-specific lipid-transfer protein (nsL-TP), also known as sterol carrier protein 2 (SCP2), is a small (M(r) 13,000) basic protein which catalyzes in vitro the transfer of a great variety of lipids, including cholesterol, between membranes. Inherent to this transfer activity, the protein stimulates in vitro various aspects of cholesterol metabolism. nsL-TP is synthesized as a precursor (pre-nsL-TP) with a leader sequence of 20 amino acid residues. It appears that the peroxisomes play an important role in the conversion of pre-nsL-TP into the mature form. In fact, nsL-TP appears to be mainly present in peroxisomes as shown by immunogold labeling of rat liver, adrenals and testes using the anti-nsL-TP antibody. However, interpretation of the data is complicated by the fact that the antibody raised against nsL-TP also reacts with a protein with a M(r) of 58,000. From cDNA analysis it became apparent that the cross-reactive 58-kDa protein contains the complete sequence of pre-nsL-TP at its C-terminus. However, pre-nsL TP and the 58-kDa protein are synthesized from different mRNAs. Interestingly, the N-terminal part of the 58-kDa protein was found to have significant sequence similarity with 3-oxoacyl-CoA thiolase. Both pre-nsL-TP and the 58-kDa protein contain the C-terminal peroxisomal targeting tripeptide Ala-Lys-Leu. However, as shown by subcellular fractionation studies the 58-kDa protein is exclusively localized in the peroxisomes whilst nsL-TP is not only detected in the peroxisomes but also in other subcellular fractions. Moreover, a membrane-bound form of nsL-TP was detected. This membrane-bound form is present at the cytosolic side of the membranes. The physiological function of nsL-TP is still unclear; some recent developments are discussed briefly in the last part of this review. PMID- 8507682 TI - Ultrastructural aspects of the biogenesis of peroxisomes in rat liver. AB - A model summarizing our current concepts on the ultrastructural basis of the biogenesis of peroxisomes is presented. Accordingly, the initial stage of de novo build-up of peroxisomes is characterized by the formation of myelin-like figures and membranous attachments onto the surface of pre-existing peroxisomes. Such membranous structures may provide the appropriate lipid environment for the incorporation of peroxisomal membrane proteins and subsequently become the preferential sites for import of newly synthesized matrix proteins. After the import the membranous structures develop into small peroxisomes which may remain attached briefly to the larger particles but eventually separate to become new peroxisomes. Whereas some matrix proteins such as catalase are distributed in all newly formed peroxisomes, other ones like urate oxidase and D-amino acid oxidase are compartmentalized only in some of them, giving rise to heterogeneity of peroxisomes. PMID- 8507683 TI - Two complementary approaches to study peroxisome biogenesis in Saccharomyces cerevisiae: forward and reversed genetics. AB - In order to investigate the mechanisms of peroxisome biogenesis and to identify components of the peroxisomal import machinery we studied these processes in the yeast Saccharomyces cerevisiae. The forward genetic approach has led to pas mutants (peroxisomal assembly) which fall into 12 complementation groups and allowed to identify 10 of the corresponding wild-type PAS genes (PAS 1-7, 9, 11 and 12). Recent sequence analysis data of some of these genes are beginning to provide first hints as to the possible function of their gene products. The PAS genes and their corresponding mutants are presently used to address some important questions of peroxisomal biogenesis. Reversed genetics has been started as a complementary approach to characterize especially the function of peroxisomal membrane proteins. For this purpose we describe a technique to isolate highly purified peroxisomes. This led to the identification of 21 polypeptides as constituents of this organelle. Some of them are presently sequenced. PMID- 8507684 TI - Fatty acid degradation in plant peroxisomes: function and biosynthesis of the enzymes involved. AB - In plants, the fatty acid oxidation enzyme apparatus is exclusively located within glyoxysomes or peroxisomes. Following the formation of the CoA-ester, the machinery for the degradation of endogenous fatty acids consists of acyl-CoA oxidase, D-3-hydroxyacyl-CoA hydrolyase, 2,3-enoyl-CoA isomerase, isoenzymes of the multifunctional protein and thiolase. The multiple location of particular enzyme activities on different species of protein is discussed in detail. In cucumber cotyledons, the multifunctional protein exhibits a C-terminal targeting signal, -PRM like other glyoxysomal or leaf peroxisomal proteins. In contrast, proteolytic modification takes place at the N-terminus of thiolase and malate dehydrogenase. Thus, distinct mechanisms are envisaged to take place during the transfer of the cytosolic precursor into glyoxysomes prior to the intra organellar assembly of the mature enzyme. PMID- 8507685 TI - The glycosomes of the Kinetoplastida. AB - Glycosomes are the microbodies of the organisms belonging to the order of the Kinetoplastida, comprising trypanosomes and leishmanias, both pathogens to man. The organelles sequester a number of glycolytic enzymes that are normally located in the cytosol in other eukaryotic organisms, and share some enzymes with peroxisomes and glyoxysomes of other protists, plants and animals. Proteins enter the glycosome by a mechanism of post-translational translocation which involves in some, but not all, cases a C-terminal oligopeptide sequence. PMID- 8507687 TI - Structure and expression of the genes encoding peroxisomal beta-oxidation enzymes. AB - To investigate the mechanism of induction of the peroxisomal beta-oxidation enzymes by peroxisome proliferators, genes of these enzymes were cloned from rat liver and their structures analyzed. The acyl-CoA oxidase gene was found to produce two forms of the enzyme differing in their amino acid sequences in a limited region, through alternative splicing of the two copies of the third exon. The amino acid sequence of the bifunctional enzyme suggests, compared with those of its mitochondrial counterparts, that the enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase activities are located on the amino- and the carboxyl sides, respectively. Two copies of the 3-ketoacyl-CoA thiolase gene were identified per haploid genome. One gene named A is constitutive and encodes a thiolase precursor carrying 36 amino acid residues of amino-terminal presequence, whereas the other, termed B, is remarkably induced by peroxisome proliferators and specifies a precursor having a 26-residue presequence. Functional analysis of the upstream sequence of the acyl-CoA oxidase gene revealed three functionally different regions, one of which had the character of ciprofibrate-responsive enhancer. In this region, two sequences were identified as binding-sites of rat liver nuclear proteins. A gene transfection study indicated that these sequence elements (termed A and B) play important roles in the induction of the gene, the former acting positively whereas the latter probably is acting negatively. PMID- 8507686 TI - Biochemical properties of liver peroxisomes from rat, guinea pig and human species and the influence of hormonal status on rat liver acyl-CoA oxidase mRNA content. AB - Liver peroxisomes from three different species, rat, guinea pig and man, have been purified by ultracentrifugation on a discontinuous Nycodenz gradient. Several biochemical parameters were tested in order to compare the basic peroxisomal properties of liver from rat, a species strongly responsive to peroxisome proliferators, and guinea pig and man, two weakly responsive species. Polypeptide patterns were compared and the bands in guinea pig and man comigrating with the two major bands in rat, catalase at 66 kDa and urate oxidase at 35 kDa, appeared in low amounts. However, other polypeptides are similar throughout these species especially in guinea pig as revealed by cross immunoreactivity using an anti-rat peroxisomal protein rabbit immune serum. Specific activities of peroxisome acyl-CoA oxidase and microsome omega-lauryl hydroxylase have comparable rates in rat and guinea pig liver, but in human liver the activities are much lower. There is a cross-hybridization between acyl-CoA oxidase mRNA probed by rat liver acyl-CoA oxidase cDNA among the three species at a medium stringency. But interestingly, acyl-CoA oxidase mRNA from guinea pig and man appear to be larger in size. On the other hand, the hormonal status does not seem to have a significant effect on the rat liver acyl-CoA oxidase mRNA level suggesting at most that insulin, corticosterone and estradiol have no direct effect on acyl-CoA oxidase gene expression, which contrasts with the well-known effect of peroxisome proliferators. PMID- 8507688 TI - Thyromimetic effect of peroxisome proliferators. AB - Xenobiotic amphipathic carboxylates of varying hydrophobic backbones, known collectively as 'peroxisome proliferators' (PP), affect lipoprotein metabolism, calorigenesis, liver redox and phosphate potentials and adipose conversion. Some biological effects exerted by PP are strikingly similar to those exerted by thyroid hormones (TH). Furthermore, similarly to TH, these compounds have been recently found to induce in euthyroid as well as thyroidectomized rats or in rat hepatocytes cultured in TH-free media, liver activities classically considered as TH-dependent, eg malic enzyme (ME) and S14. The thyromimetic effect of PP could be accounted for by transcriptional activation of TH-dependent genes as verified by run-on transcription assays. The thyromimetic effect of PP was found not to be mediated by the TH nuclear receptor. Moreover, in contrast to TH, PP were ineffective as thyromimetic agents in the rat heart or pituitary cells, suggesting a tissue specificity different from that of TH. The overall thyromimetic effect of PP appears to involve transcriptional activation of TH dependent genes, yet being mediated by a novel transduction pathway. PMID- 8507689 TI - Toxicity of peroxisome proliferators. AB - Peroxisome proliferators are not a chemical class of compounds. They do not have a similar chemical structure but all induce characteristic effects in the liver of treated rats or mice. They produce within a few days a striking dose-dependent hepatomegaly accompanied by a characteristic proliferation of the peroxisomal and microsomal compartment as assessed morphologically and biochemically. Such effects are not observed in other species including human. In addition, life-long feeding of the susceptible laboratory animals results in the formation of liver tumor. The effects induced in subchronic studies can be reproduced and investigated in cultured hepatocytes, the target cells. The species specificity is observed with all peroxisome proliferators, and by large the effects observed in subchronic studies are reversible. The hepatocarcinogenesis by peroxisome proliferators is not fully understood, because these compounds are not directly genotoxic, but the understanding of their tumor promotor potential has some implications for the toxicological testing and risk assessment. PMID- 8507690 TI - Adrenoleukodystrophy gene: unexpected homology to a protein involved in peroxisome biogenesis. AB - Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by a progressive demyelination of the central nervous system and adrenal insufficiency. Clinical phenotypes of different severity are frequently observed within the same kindred. ALD is characterized biochemically by the accumulation of very-long-chain fatty acids (VLCFA) due to an impairment in the beta-oxidation of these fatty acids in peroxisome. From the observation that oxidation of VLCFA CoA is normal in fibroblasts from patients with ALD, it was concluded that the gene coding for VLCFA-CoA synthetase was a candidate gene for ALD. Using positional cloning strategies, we have identified a gene which was found partially deleted in 7% of 85 independent patients with ALD. The predicted protein (ALDP) sequence shows significant homology to the 70-kDa peroxisomal membrane protein which is involved in peroxisome biogenesis and belongs to the 'ATP binding' superfamily of transporters. ALDP thus encodes a putative peroxisomal transporter molecule which may be involved in the import or anchoring of VLCFA-CoA synthetase. PMID- 8507691 TI - Update on genetic and molecular investigations of diseases with general impairment of peroxisomal functions. AB - A group of genetically determined peroxisomal diseases is characterized by both multiple enzymatic deficiencies and abnormal structural features of the organelle. The primary cause of the phenotypes is likely to involve peroxisome assembly impairment. Complementation analyses performed on fibroblasts of patients revealed the existence of at least eight groups that do not reflect the clinical classifications. Recently, the use of experimental models led to the identification of a gene encoding for a peroxisomal membrane protein (PAF-1) in which a mutation was associated with the altered phenotype in a complementation group of the Zellweger syndrome (paradigm of these diseases). Also revealed in Zellweger probands are mutations of a gene encoding another peroxisomal protein (PMP70). PMID- 8507692 TI - Primary hyperoxaluria type 1 and peroxisome-to-mitochondrion mistargeting of alanine:glyoxylate aminotransferase. AB - Under the influence of dietary selection pressure, the intracellular compartmentalization of alanine:glyoxylate aminotransferase (AGT) has changed on many occasions during the evolution of mammals. In some mammals, AGT is peroxisomal in others it is mainly mitochondrial while in yet others it is more or-less equally divided between both organelles. Although in normal human liver AGT is usually found exclusively within the peroxisomes, in some individuals a small proportion (approximately 5%) is found also in the mitochondria. This apparently trivial intracellular redistribution of AGT is caused by the presence of a Pro11Leu polymorphism which allows the N-terminus of AGT to fold into a conformation (ie a positively-charged amphiphilic alpha-helix) which functions as a mitochondrial targeting sequence. In one third of patients with the autosomal recessive disease primary hyperoxaluria type 1, there is a further redistribution of AGT so that the great majority (approximately 90%) is located in the mitochondria and only a small minority (10%) in the peroxisomes. AGT cannot fulfil its proper metabolic role in human liver (ie glyoxylate detoxification) when located in the mitochondria. The erroneous compartmentalization is due to the presence of a Gly170Arg mutation superimposed upon the Pro11Leu polymorphism. The Gly170Arg mutation appears to have no direct effect on mitochondrial targeting and is predicted to enhance mitochondrial import of AGT by interfering with its peroxisomal targeting and/or import. The mitochondrial targeting sequence generated by the Pro11Leu polymorphism is not homologous to that found in the AGT of other mammals which localise AGT within the mitochondria normally. The identity of the peroxisomal targeting sequence in AGT is unknown, but the Gly170Arg mutation is found in a highly conserved region of the protein which might be involved in some aspects of the peroxisomal import pathway for AGT. PMID- 8507693 TI - Blood selenium or serum selenium? PMID- 8507694 TI - Comparison of porcine alveolar macrophages and CL 2621 for the detection of porcine reproductive and respiratory syndrome (PRRS) virus and anti-PRRS antibody. AB - The American and European strains of porcine reproductive and respiratory syndrome (PRRS) virus were initially isolated in an established cell line (CL 2621) and porcine alveolar macrophages (PAM), respectively. Subsequent isolation of American strains of this virus in PAM has also been reported. To determine their relative sensitivity for virus isolation, both PAM and CL 2621 cells were inoculated with 98 tissue specimens and 73 serum samples from animals suspected of having PRRS. Four of the 98 tissue samples yielded virus in both cell types, whereas 7 samples were positive only in PAM and 4 samples only in CL 2621. Of the 73 serum samples tested, 18 were positive in PAM of which only 2 were positive in CL 2621. Additionally, 82 isolates obtained initially in CL 2621 were inoculated in PAM cells, and 18 strains isolated originally in PAM were inoculated in CL 2621. Of the 82 CL 2621 isolates, 25 could not be propagated on PAM. Of the 57 that replicated in PAM, as detected by a positive test on indirect fluorescent antibody test, only 28 produced cytopathic effects and 29 did not. Of the 18 PAM isolates, 5 did not grow on CL 2621. Although PAM were relatively more sensitive for virus isolation, their failure to support the growth of certain strains of PRRS virus indicates the existence of variants among PRRS virus strains, and both PAM and CL 2621 should be used for virus isolation from clinical samples. In addition, the sensitivity of these 2 cell types was compared for the detection of fluorescent antibodies to PRRS virus using 179 serum samples from PRRS-infected animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507696 TI - Mycoplasma bovis associated with decubital abscesses in Holstein calves. AB - Between April of 1990 and March of 1992, calves on a Holstein calf ranch experienced subcutaneous decubital abscesses involving the brisket region, dorsal aspect of the carpus, and lateral aspect of the stifle joints. Fifty out of 2,500 (2%) Holstein calves between the ages of 3 and 12 weeks were affected. Needle aspirates of brisket abscesses from 8 calves and 6 live or dead calves with 1 or more decubital abscesses were submitted for examination. Two of the 6 calves in addition had bronchopneumonia. Mycoplasma bovis was isolated from all abscesses and 1 lung. Formalin fixed tissues taken from the affected areas also revealed M. bovis by immunoperoxidase staining. No evidence of joint involvement was apparent, and no mycoplasma was isolated from the joints adjacent to affected areas. Attempts to isolate mycoplasma from milk and environmental samples were unsuccessful. PMID- 8507695 TI - Evaluation of an ELISA for detection of ovine progressive pneumonia antibodies using a recombinant transmembrane envelope protein. AB - An enzyme-linked immunosorbent assay (ELISA) was developed using a recombinant protein corresponding to the N'-terminal hydrophilic region of transmembrane glycoprotein (TM) of ovine lentivirus. This assay reproducibly detected antibodies in sera from 207 of 212 ovine progressive pneumonia (OPP) virus infected sheep, and the recombinant TM ELISA accurately identified 26% (35 vs. 9) more seropositive samples than did the agar gel immunodiffusion test when applied to 100 sera from an infected flock. This assay also yielded no false-positive results in 14 true negative sera. Results of these experiments were further confirmed by the recombinant TM and recombinant p25 Western blot assay. A single recombinant TM antigen, as the coating antigen in ELISA, can be used successfully for the detection of OPP virus-infected animals and can improve the sensitivity and specificity for OPP diagnosis. PMID- 8507697 TI - Erysipelas in caged laying chickens and suspected erysipeloid in animal caretakers. AB - Erysipelas was diagnosed in 2 succeeding caged layer flocks housed in the same building and was characterized clinically by sudden death. At necropsy, lesions comprised generalized congestion, hemorrhages in the skeletal muscles and visceral organs, and swelling of liver, spleen, and kidney with or without large irregular zones of necrosis. Focal to massive hepatic necrosis was seen histologically with minimal or no inflammatory reaction. Erysipelothrix rhusiopathiae was cultured from internal organs of affected birds in both outbreaks. Medication with penicillin in the feed controlled the mortality, but relapse occurred after cessation of medication. Two attendants who handled the dead birds in this building developed a painful localized infection of the fingers that later spread to the regional lymph node. The infection responded when antibiotic therapy for erysipeloid was initiated. PMID- 8507698 TI - Hemorrhagic diathesis associated with a hereditary platelet disorder in Simmental cattle. AB - A severe bleeding disorder in Simmental cattle has been described in widespread locations in the USA and Canada. The clinical findings are consistent with a hemophilia-like disease or, more precisely, a hereditary hemorrhagic diathesis and include spontaneous epistaxis, hematuria, and excessive bleeding associated with trauma or standard management procedures such as tattooing, ear tagging, and castration. A preliminary investigation of this defect showed that blood-platelet numbers and coagulation profiles of affected cattle were normal. Affected animals have a marked dysfunction of platelets (thrombopathy), termed Simmental hereditary thrombopathy. The defect is very similar or identical to that described in the same breed by 2 other laboratories. PMID- 8507699 TI - Serum triiodothyronine and thyroxine concentrations in neonatal llamas. AB - Total serum triiodothyronine (T3) and thyroxine (T4) concentrations were assayed in neonatal llamas from birth to 90 days of age. T3 concentrations were high at birth and increased from birth to approximately 6 days, then gradually decreased. T4 concentrations were highest at time of birth and decreased gradually over the 90-day period. PMID- 8507700 TI - Ovine myeloencephalitis-leukomyelomalacia associated with a Sarcocystis-like protozoan. AB - Bilateral pelvic limb paresis developed in 7 of 15 10-month-old Blueface Leicester ram lambs on a mixed enterprise farm in the North of England. Clinical signs were principally mild to severe paresis of the pelvic limbs. Two mildly affected lambs recovered. Multifocal spinal cord white matter edema and necrosis, glial nodules, and mild to moderate nonsuppurative encephalomyelitis were the principal findings in 3 severely paretic lambs examined histologically. Protozoan bodies (12.7-23.0 microns) that stained immunocytochemically for Sarcocystis epitopes were in spinal cord glial cells of 2 of 3 lambs. Protozoa did not react immunocytochemically with anti-Toxoplasma gondii or Neospora canium antisera. Serology indicated there was recent exposure to Sarcocystis spp. in some surviving lambs. These cases resembled those in previous reports of paresis due to an unidentified Sarcocystis-like protozoan in sheep (ovine protozoan myeloencephalitis) in the British Isles, the USA, France, Australia, and New Zealand. PMID- 8507701 TI - Eosinophilic mediastinitis, myositis, pleuritis, and pneumonia of cattle associated with migration of first-instar larvae of Hypoderma lineatum. AB - Migrating first-instar larvae of Hypoderma lineatum are a frequent cause of focal inflammatory lesions in connective tissues of the mediastinum, parietal and visceral pleura, peritoneum, lungs, diaphragm, and other loci. The lesions are characterized grossly by foci of yellowish or greenish gelatinous edema and microscopically by infiltration of the edematous tissue by a dense array of eosinophils. Lesions were recognized during a period of several weeks in late spring; the timing was attributable to events in the life cycle of the fly. The larvae, which were small (approximately 1 x 4.5 mm), transparent, and unobtrusive, were recovered from lesions in 12 of 20 cattle in which careful parasitologic examination was made. PMID- 8507702 TI - Fumonisin toxicosis in swine: clinical and pathologic findings. AB - From a series of experimental studies with pigs (12-16 kg), either pulmonary edema or liver failure emerged as a distinct pathogenetic expression of fumonisin B1 (FB1) toxicosis. The primary determinant as to which pathogenetic consequence developed was the quantity (dose) of the mycotoxin fed or intubated per kilogram of body weight per day. Pigs intubated with a minimum of 16 mg FB1/kg/day developed severe interlobular edema with or without hydrothorax and variably severe pulmonary edema. Pigs intubated with < 16 mg FB1/kg/day or pigs fed diets containing 200 mg FB1/kg of feed developed marked icterus and hepatocellular necrosis. The spectrum of degrees of severity of pulmonary edema observed in the experimental pigs allowed rational speculation regarding evolution of the pathologic changes. PMID- 8507703 TI - An HPLC method for the detection of ergot in ground and pelleted feeds. AB - A high performance liquid chromatography (HPLC) method is described for detecting ergot in ground or pelleted forages and grains. Samples were extracted with alkaline chloroform, filtered, and applied to silica gel/organic binder cleanup columns. Following elution of pigments with acetone: chloroform, ergopeptine alkaloids were eluted with methanol and analyzed by HPLC with fluorescence detection. Average recovery of ergotamine, the major ergopeptine alkaloid produced by Claviceps, was 93%, with a relative standard deviation of 4.9%. The detection limit of ergotamine was approximately 50 ppb in all feedstuffs. Confirmation of ergopeptine alkaloids was accomplished by treating the parent ergopeptine alkaloids with 0.2% acetic acid to produce their -inine isomers and reexamining by HPLC with fluorescence detection or silica gel/organic binder column cleanup in combination with tandem mass spectroscopy. The method described is a valid alternative to microscopic inspection for detecting ergot contamination in ground or pelleted feedstuffs. PMID- 8507704 TI - Rabies in a vaccinated canine exhibiting generalized demodicosis. PMID- 8507705 TI - Isolation of an iridovirus from farm-raised gouramis (Trichogaster trichopterus) with fatal disease. PMID- 8507706 TI - Seroprevalence of indirect fluorescent antibody to porcine reproductive and respiratory syndrome virus in selected swine herds. PMID- 8507707 TI - Evaluation of latex agglutination for detecting chlamydial antibody activity in psittacine bird sera by comparison with direct complement fixation. PMID- 8507708 TI - Pleuropneumonia in swine associated with a urease-negative variant of Actinobacillus pleuropneumoniae serotype 1. PMID- 8507709 TI - Outer membrane proteins of Fusobacterium necrophorum biovars A, AB and B: their taxonomic relationship to F. necrophorum subspecies necrophorum and F. necrophorum subspecies funduliforme. PMID- 8507710 TI - Canine medullary thyroid carcinoma with unusual distant metastases. PMID- 8507711 TI - Aortic-iliac thromboembolism as an uncommon sequel to Staphylococcus aureus valvular endocarditis in a calf. PMID- 8507712 TI - Sarcocystosis with involvement of the central nervous system in lambs. PMID- 8507713 TI - Intramuscular Sarcocystis in two beluga whales and an Atlantic white-sided dolphin from the St. Lawrence estuary, Quebec, Canada. PMID- 8507714 TI - Lasalocid toxicosis in dairy calves. PMID- 8507715 TI - Review of spinal muscular atrophy (SMA) in brown Swiss cattle. PMID- 8507716 TI - Interleukin-6, a new target for therapy in multiple myeloma? AB - During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo observations that interleukin-6 is involved in the pathogenesis of multiple myeloma, and the implications of these findings for the development of new therapeutic strategies are discussed. PMID- 8507717 TI - Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics. AB - In a prospective study of 33 newly diagnosed patients with acute myeloid leukemia (AML), we analyzed the relationship of proliferation parameters with clinical parameters, response to induction therapy, and survival. The median follow-up was 26 months. The proliferative capacity of the leukemic progenitor cells was studied using colony-forming assays (number of colony-forming units, growth pattern, and spontaneous clonogenic growth capacity). The cell kinetic parameters of the bone marrow blasts were determined by in vivo labeling with iododeoxyuridine and subsequent flow cytometry: labeling index (LI), DNA synthesis time (Ts), potential doubling time. No or only weak relationships were observed between the experimental and clinical parameters such as age, sex, % blasts, white blood cell count, FAB subtype, cytogenetics, and % CD 34+ cells. This suggests that clonogenic growth and cell cycle kinetics of bone marrow blasts are independent cell biologic properties of AML. No association between the proliferation parameters and induction response rate was noticed. Analysis of the overall survival and event-free survival revealed trends to longer survival rates in patients with a below-median LI (< or = 7.6%) and below-median Ts value (< or = 14.3 h). These trends were more pronounced in the group of de novo AML (n = 23), where the prolonged event-free survival in patients with below-median Ts reached statistical significance (p = 0.02). None of the other parameters appeared significantly correlated with survival, although there was a trend to longer survival rates in patients who had no spontaneous clonogenic growth capacity (p = 0.13). In conclusion, proliferation parameters in leukemic cells provide additional information on the cell biologic characteristics of AML, and these parameters may have prognostic value for response and duration of survival in AML. PMID- 8507718 TI - Is there still a role for low-dose cytosine arabinoside in de novo acute myeloid leukemia in the elderly? A report on 77 cases. AB - Seventy-seven elderly patients (median age 72, range 59-85) with de novo AML were treated with low-dose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were < or = 9 months, and 12/16 were < or = 4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR+PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index > or = 60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an "unfavorable" karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities). PMID- 8507719 TI - Sustained complete hematological remission in essential thrombocythemia after discontinuation of long-term alpha-IFN treatment. AB - In essential thrombocythemia patients alpha-IFN rapidly reduces platelet count, and it is also able to maintain a low count during long-term treatment. In order to verify if long-term IFN treatment can produce sustained remission in selected patients, we decided to suspend IFN treatment in two subsets of 21 patients on long-term alpha-IFN treatment: (a) all six patients who had shown a platelet count below 450 x 10(9)/l for at least 2 months with 3 MU once a week; (b) three patients who had shown the same platelet count for at least 2 months with 3 MU three times a week. After withdrawal of alpha-IFN treatment, a rapid increase in the platelet count was observed in all three patients requiring 3 MU three times a week. Three of the six patients treated with 3 MU once a week are still free of symptoms and have been in complete hematological remission (platelet count below 450 x 10(9)/l) for 9+, 13+, and 14+ months, respectively. As far as the three remaining cases are concerned, one was not assessable because of loss to follow up, while the other two relapsed after 1 and 2 months. We believe that the three cases of sustained remission might be the result of a long-term tumor load reduction produced by the alpha-IFN treatment. Finally, the factor best able to predict sustained, unmaintained remission seems to be the clinical response to a low dose of alpha-IFN during the maintenance phase, rather than disease features prior to treatment. PMID- 8507720 TI - MCNU in the treatment of essential thrombocythemia--a pilot study. AB - The efficacy of a single dose of MCNU 150 mg was evaluated in nine symptomatic patients with essential thrombocythemia (ET). As the platelet counts increased during the following 4 weeks, an extra dose of 100 mg of MCNU was administered to three patients. All patients had thrombotic or hemorrhagic complications. Seven patients responded. The mean platelet count decreased to below 1.0 x 10(12)/l within 5 weeks; it reached its lowest level (0.35 x 10(12)/l) at 6 weeks and became stable at less than 1.0 x 10(12)/l without further therapy for 12 weeks in all patients. Thrombotic and hemorrhagic complications ameliorated within 4 weeks in all patients. Our study indicates that MCNU acts as a platelet-reducing agent in patients with ET. PMID- 8507721 TI - Self-treatment with desmopressin intranasal spray in patients with bleeding disorders: effect on bleeding symptoms and socioeconomic factors. AB - Desmopressin (1-desamino-8-D-arginine vasopressin), an established hemostatic agent for the treatment of bleeding in mild hemophilia A, von Willebrand's disease, or platelet disorders, has mostly been given parenterally as intravenous or subcutaneous injections. Intranasal administration by spray has been shown to yield significant and highly reproducible increases in the plasma concentrations of factor VIII and von Willebrand factor and platelet adhesiveness, and to be suitable for self-administration at home, as it is easy to handle and does not involve the use of needles. This paper presents data from a questionnaire answered by 78 patients with mild hemophilia A, von Willebrand's disease, or platelet disorders, who had used the spray at home to treat bleeding symptoms. The patients experienced decreased blood loss and shortened duration of epistaxis, menorrhagia, tissue bleeding, and bleeding in connection with minor surgery or tooth extraction. The use of factor VIII concentrates was diminished, as were the number of visits to outpatient care and absence from school or work. PMID- 8507722 TI - Comparison of the protein and DNA approaches for the characterization of a beta globin chain variant, hemoglobin Cocody [beta 21 (B3) Asp--->Asn], in a Caucasian patient. AB - Over the past few years, the methodologies used for the identification of hemoglobin A variants have been greatly improved. Both the protein- and DNA-based strategies have their own advantages and limitations. In this report we illustrate the use of both assays for the characterization of a hemoglobin Cocody variant in a women of Spanish descent. After evaluating the mobility value matrix of the abnormal hemoglobin, the amino acid transition was determined by HPLC and micro-sequencing of the protein. The beta 21 Asp was shown to be substituted by an Asn. At the DNA level, the only nucleotide replacement responsible for this amino acid substitution is GAT--->AAT at codon 21. The analysis of the beta globin gene by denaturing gradient gel electrophoresis (DGGE) method showed that the mutation was situated in a fragment including exon 1. The hemoglobin variant was then identified to be hemoglobin Cocody by DNA sequencing of this fragment. PMID- 8507723 TI - Tuberculosis update. PMID- 8507724 TI - Moments in time. PMID- 8507725 TI - Unit-based quality assurance: a necessary component of ET nursing practice. AB - A unit-based quality assurance tool has been developed to facilitate the monitoring of nursing care given to patients with ostomies. The tool consists of 23 clinical indicators that measure structure, process, and outcome issues specific to the patient with a fecal or a urinary diversion. Clinical indicators were derived from the WOCN's Standards of Care for Patient with Colostomy, Ileostomy, and Urinary Diversion. In addition, the tool was reviewed for content validity by ET nurses not involved in the original tool development. The data are retrieved through patient observation, patient interview, record review, nurse interview, nurse observation, and check on equipment availability. Results are reflective of care given to patients by staff nurses and nursing assistants, as well as by ET nurses. Current limitations include the fact that the tool has not been tested for transportability for use in other institutions. PMID- 8507726 TI - An external urine-collection device for women: a clinical trial. AB - Urinary incontinence imposes physical, social, and economic hardships on those who face it. For many, pads and diapers are invaluable. Many types of condom catheters are available for men, but there are few similar devices for women. For the past 10 years, we have been developing an external urine-collection device for women. This device adheres between the labia to surround the urethra. The purposes of this first, descriptive clinical trial were (1) to examine the device for fit, urine containment, maintenance of vulvar skin integrity, and comfort; and (2) to describe microorganism changes to urine and periurethral and vaginal tissue in women wearing the device. PMID- 8507727 TI - Current status of ileoanal reservoirs: 1992. AB - Restorative proctocolectomy with ileoanal reservoir has been a significant development in the surgical treatment of mucosal ulcerative colitis and familial adenomatous polyposis. It enables excision of the diseased colorectal mucosa with preservation of continence and avoidance of a permanent stoma. The surgical techniques, criteria for patient selection, and understanding of the physiology and outcome of the procedure, however, continue to evolve. PMID- 8507728 TI - The aging immune system and common infections in elderly patients. AB - The number of elderly persons in the United States has increased to 12.5% of the population, and diseases affecting this age group have also risen. Infections of the respiratory, urinary, and integumentary systems, commonly seen in elderly patients, are a leading cause of death. Changes in the immune system cannot be prevented; however, nursing interventions may reduce the incidence of infection. An understanding of the changes in the immune system and careful nursing assessments may help the nurse to detect infections in elderly patients earlier. PMID- 8507729 TI - Clinical benefit of a hydrocolloid dressing in closed surgical wounds. AB - A prospective, multicenter trial evaluated the clinical benefits of a new hydrocolloid wound dressing material (DuoDERM Extrathin; ConvaTec International, Skillman, N.J.) in a postoperative setting. Criteria assessed were patient quality of life (adherence of the dressing, showering or bathing possibilities, aspects of dressing changes), safety (incidence of infection), effectiveness (healing time), and clinical utility (ease of application and removal, ease of inspecting the wound through the dressing). Ninety-five patients with 102 sutured wounds were enrolled in the study during a period of 18 months. Forty-three wounds were in anatomic areas considered difficult to dress with such conventional materials as gauze and tape. The overall incidence of infection was 2%; the dressing was found not to be a causal factor. In five wounds, treatment had to be stopped before scheduled. Comfort rating by the patients and the investigators were "good" and "very good" in 95% and 92% of cases, respectively. A mean of 1.56 dressings per wound was used until removal of the sutures. Because of the reduction in the necessary number of dressing changes, hydrocolloid dressing may help in reducing treatment costs. PMID- 8507730 TI - Hope and wound healing. AB - Multiple factors, including psychologic factors, affect the quality of wound healing. The ET nurse works with a patient population for whom the concept of hope is particularly relevant. Little literature is related specifically to the impact of hope or hopelessness on wound healing. The purpose of this article is to explore the concept of hope and its possible relationship to wound healing. PMID- 8507731 TI - Caring for the caretakers: the patient's family. AB - The increasing complexity of health care, as well as life in general, in America places increasing burdens on families with ill members. The growing elderly, multigenerational, and multiresponsibility families, too much distance and too little time, too many demands, too few supports, and lack of resources strain family life when illness occurs. Yet illness is a family matter. The disease entities, body-altering operations, and prognoses of the patients managed by ET nurses are stressful for both patient and family. The ET nurse can play a central role in supporting the family in the quest for positive outcomes and quality for all. The case presentation demonstrates that appropriate assessment and intervention often go beyond dealing with the stoma. Family systems theory concepts are discussed as a theoretic framework for family intervention. PMID- 8507732 TI - [Biochemical paths for regulating hormone-sensitive cells]. AB - The main causes of alterations in cell sensitivity to steroid hormones were studied during malignant growth and upon ageing. In many cases studied the decreased sensitivity of cells to steroids was reversible and unrelated to changes in the receptor system of the cell. Based on the data obtained, a hypothesis was proposed concerning the multifunctional regulation of cell sensitivity to hormones. Within the framework of this hypothesis the sensitivity of cells to hormones is regulated by both changes in the receptor system responsible for hormonal signal transmission and by changes in the activity of hormone-dependent intracellular enzymatic systems. The role of target cell microenvironment in the formation of the ultimate cell response to hormonal stimuli is discussed. PMID- 8507733 TI - [Activity of the antioxidant system of rat liver in benzidine poisoning and administration of enomelanin]. AB - It has been shown that benzidine administered in vivo attenuates the protective effect of the antioxidant system manifested as a reduction of the total antioxidant activity of rat liver cytosol and decreasing activities of superoxide dismutase and catalase. Enomelanin promotes the reconstitution of the superoxide dismutase activity. The data obtained suggest that the toxic effect of benzidine may be due to disturbances in the antioxidant protective mechanisms of liver cells responsible for the control over the free radical processes occurring in those cells. PMID- 8507734 TI - [Damage to calcium ion-loaded mitochondria by fatty acids and the protective effect of carnitine]. AB - The effect of fatty acids and L-carnitine on Ca2+ retention in rat liver mitochondria have been studied. Ca(2+)-retention was estimated as a sum of consecutive Ca2+ additions which leaded to transient stimulation of respiration coupled with influx of Ca2+ L-carnitine increases the Ca(2+)-retention; such an effect requires ATP. The Ca(2+)-retention was increased in the presence of 50 microM ATP or ADP. In all cases carboxyatractylate prevented the increase in Ca(2+)-retention. Palmitate and FCCP added at concentrations producing similar stimulating effect on respiration inhibit Ca(2+)-retention to about the same degree. The effect of palmitate is strongly diminished by L-carnitine. Again, the L-carnitine effect requires ATP. The data obtained suggest that the protonophoric effect of fatty acid plays a crucial role in Ca(2+)-dependent damage of mitochondria. PMID- 8507735 TI - [Distribution of oligonucleotide derivatives and their stability in murine tissues]. AB - Distribution and stability of benzyl-[5'-32P] phosphoramides of oligonucleotides and their phosphorothioate analogs were investigated. Oligonucleotide derivatives are distributed among all murine organs, the maximal concentration being observed in the liver and kidney, and minimal in the brain. Intravenous and intraperitoneal injections resulted in a faster distribution of oligonucleotides among the tissues than subcutaneous injections. Hydrolysis rate varied from tissue to tissue, and in 30 min after injection 5 to 50% of intact oligonucleotides were found. Hydrolysis did not depend on the injected dose in the range of 0.15-150 nmol per mouse. The 3'-terminal cholesterol groups protected the oligonucleotides considerably. In the blood stream and pancreas phosphorothioate oligonucleotides showed much higher stability than their phosphodiester counterparts. A protein interacting specifically with the oligonucleotides was discovered in the liver, kidney and pancreas. PMID- 8507736 TI - [Metabolites of the propionate pathway as regulators of fatty and dicarboxylic acid oxidation in liver mitochondria]. AB - The functioning of the propionate pathway of oxidation substrate metabolism in the norm and under vitamin B12 deficiency has been studied. This pathway has been shown to play an important role in oxidative processes occurring in normal organisms, for its inhibition in B12-deficient animals is associated with a reduction of respiration as well as with noticeable decreases in palmitoylcarnitine and succinate oxidation rates and oxidation phosphorylation coupling. Succinate, the end product of the propionate pathway, normalizes the respiration and restores the rate of palmitoylcarnitine oxidation in B12 deficient animals, which is suggestive of its crucial role in the propionate pathway. In vivo propionate inhibits, whereas methyl malonate stimulates palmitoylcarnitine respiration, however only in intact animals. In B12-deficient animals the sensitivity to these metabolites is decreased. PMID- 8507737 TI - [The effects of a cardioactive hypothalamic neurohormone on the isolated rat heart]. AB - On the isolated perfused by Langendorf at heart the cardioactive hypothalamic neurohormone NG3a (2 x 10(-5) g/ml) significantly decreased the coronary flow rate; the effect persisted during 5-10 min, after that the second phase appeared which was expressed by the increase of coronary flow rate. The maximum effect was 122% compared with control. The second phase appeared in 30-45 min after infusion of NG3a. NG3a did not influence the heart rate, but sometimes (7.3% cases) during the maximum increase of coronary flow the bradyarrhythmia was registered. It has been concluded that NG3a influences directly the coronary vessels. PMID- 8507739 TI - [The autodeoxygenation of hemoglobin]. AB - The incubation of hemoglobin solutions without air contacts at room temperature with addition of antibiotics is accompanied by decrease of oxy form and accumulation of desoxy form. The content of methemoglobin changes at a less degree. The increase of the temperature accelerates the process, the acidification of solutions decelerates it. PMID- 8507738 TI - [4-Androstene-3,17-dione metabolism in vitro in the liver microsomes of species of bullhead endemic to Lake Baikal under normal conditions and in mono-oxygenase induction by 3-methylcholanthrene and aroclor 1254]. AB - The metabolism in vitro of 4-androstene 3,17-dione--one of the steroid hormones- has been studied in liver microsomes of three species of bullhead: Cottocomephorus grewingki Dyb., Paracottus Kneri Dyb., Paracottus Kessleri Dyb. from Lake Baikal under norm and under induction of monooxygenases by 3 methylcholanthrene and arochlore 1254. The metabolism in vitro 4-androstene 3,17 dione in liver microsomes depends on fish sex, species and gonadal maturation. The rate of androstendione hydroxylation reliably decreases at monooxydase system induction of endoplasmic reticulum in bullhead liver before spawning and during spawning periods by 3-methylcholanthrene and arochlore 1254. PMID- 8507740 TI - [The systems modelling of the processes of body adaptation to environmental changes under normal conditions and in pathology]. AB - A model of organism adaptation under its normal functioning, being transferred without any conceptual changes into the adaptation model to the stimulating actions, at which the organism malfunctions and is forced to transfer to the regime of pathology which is considered to be the only possible regime for extreme conditions. As examples the cases of adaptation to the instantaneous and periodic changes of environment are considered, the adaptation results in decay of pathologic process, the transfer from the acute to the chronic process and the adaptation with the use of medicinal preparations. The biological interpretation of parameters and dependences coming into the mathematical description of the model is given. PMID- 8507741 TI - [Parasitic mites and ticks and allergy]. AB - The review contains an of the literature on sensitivity and the clinical manifestations of allergy in human being to various parasitic and free-living mites and ticks (Sarcoptidae, Psoroptidae, Demodicidae, Ixodidae, Argasidae, Gamasina, Trombiculidae, Cheyletidae, Pygmephoridae, Tarsonemidae, Tetranychidae). The epidemiology and clinic of the allergic reactions of man to the penetration of mites and tick allergens through skin at their constant, temporal and occasional parasitizing are considered. The allergic reactions to different mite and tick allergens take both delayed and immediate type. However, the mechanism of these reactions sometimes is unknown. The mites or ticks infestations produce, as a rule, dermal allergic reactions in the atopic patients. In some cases the asthmatic component may be present. The cross reactivity between mite/tick antigens and pyroglyphid mite antigens complicates the clinic, diagnosis and treatment of allergic diseases. New data on the nature and specificity of mite and ticks allergens are presented. PMID- 8507742 TI - Effects of attention and stimulus probability on ERPs in a Go/Nogo task. AB - Event-related potentials were measured to letters presented either to the left or the right of a fixation point that were preceded by a precue that indicated the position of the upcoming letter either correctly (valid trials) or incorrectly (invalid trials). One letter required a response (Go stimulus), while the other letter required no response (Nogo stimulus). In experiment I, Nogo letters occurred only on 25% of the trials, while in experiment II, Go and Nogo letters were equiprobable. In both experiments, Nogo stimuli elicited larger N2 components and P3s with a more anterior topography than did Go stimuli. The N2 enhancement elicited by Nogo stimuli showed a frontal maximum (most markedly when Go and Nogo stimuli were equiprobable) and was significantly influenced by precue validity. These results are discussed in terms of "Response Mismatch" and action inhibition processes. PMID- 8507743 TI - Stimulus duration and the sensory memory trace: an event-related potential study. AB - The mismatch negativity (MMN) of the auditory event-related potential is elicited when a stimulus deviates from that represented by the neural memory trace developed by preceding stimuli. The effect of stimulus duration on this trace was studied by presenting sequences of 1000 Hz, 80 dB stimuli to subjects engaged in silent reading. Stimuli were, in different blocks, either of 4, 10, 30, 100 or 300 ms in duration. 5% of the stimuli were deviants which were either higher in frequency (1050 Hz) or lower in intensity (70 dB) than the standards. The "silent" period between two successive stimuli was constant at 300 ms. The minimum stimulus duration with which a distinct MMN was elicited by frequency deviants was 30 ms, but the MMN amplitude was not increased when stimulus duration was further prolonged. In contrast, the intensity MMN was elicited even when stimulus duration of 10 ms and its amplitude increased as a function of stimulus duration. Reaction times and hit percentages in response to these deviant stimuli in a separate discrimination task displayed analogous patterns of results. PMID- 8507744 TI - Internal consistency and temporal stability of classically conditioned skin conductance responses. AB - The reliability of classically conditioned skin conductance responses was investigated. Temporal stability was determined in 28 subjects studied three weeks apart (study 1), and internal consistency in 223 subjects studied once (study 2). A discriminative classical conditioning paradigm using slides with a duration of 8 s served as conditioned stimuli (CS) for an aversive unconditioned noise stimulus (study 1) or a mild unconditioned electric shock stimulus (UCS) (study 2). Electrodermal responses were recorded during a habituation phase (4 trials), an acquisition phase, where CS+ was paired repeatedly with the UCS, while CS- never was (8 trials), and an extinction phase during which shocks were withheld (8 trials each). First interval responses were measured 1-4 s after CS- onset during all phases of the experiment. During the acquisition and extinction phases, second interval responses were scored 5-9 s after CS- onset while third interval responses were determined 1-4 s after CS- termination. Internal consistency was significant for the first (rxy range 0.96-0.90), second (rxy range 0.84-0.54) and third (rxy range 0.96-0.86) skin conductance interval response. Temporal stability was highest for the first interval response (rxy range 0.72-0.37) and lowest for the second interval response (rxy range 0.51 0.05). It is concluded that the first interval skin conductance response shows adequate internal consistency and temporal stability to assess individual differences in classical conditioning. PMID- 8507745 TI - Cognitive load as a determinant of the dimensionality of the electroencephalogram: a replication study. AB - A sequel study to that reported by Gregson, Britton, Campbell and Gates (1990), partially replicating and extending findings which relate estimates of the dimensionality of the EEG to the complexity of task load in a visual scanning task, is described. The correlation dimensionality D2 of the attractor was computed using a variant of the Grassberger-Procaccia algorithm, and was shown to change in the expected direction, increasing as the task became more complicated. The effects are slight but consistent, and may be attenuated by nonstationarity over time, and by idiosyncratic factors. The results are numerically and qualitatively compatible with other recent reported studies, and support an interpretation linking brain dynamics to implied cognitive processes. PMID- 8507746 TI - Nomenclature for aerobic and facultative bacteria. PMID- 8507747 TI - Microbiology terminology update: clinically significant anaerobic gram-positive and gram-negative bacteria (excluding spirochetes). PMID- 8507748 TI - Selected medically important fungi with common synonyms and other obsolete names. PMID- 8507749 TI - Summary of current nomenclature, taxonomy, and classification of various microbial agents. Viral taxonomy. PMID- 8507750 TI - Classification of human parasites, vectors, and similar organisms. PMID- 8507751 TI - Travelers' diarrhea: approaches to prevention and treatment. PMID- 8507752 TI - Statement of the Tuberculosis Committee of the Infectious Diseases Society of America. PMID- 8507753 TI - Rocky Mountain spotted fever complicated by gangrene: report of six cases and review. AB - Although mortality due to fulminant Rocky Mountain spotted fever (RMSF) is well appreciated, the ability of the disease to cause survivors to become permanently disabled is not as widely known. We report six cases of RMSF complicated by gangrene. Although four patients required multiple limb and/or digital amputations, only one death resulted. Our review of the English-language literature revealed 23 additional cases of RMSF complicated by gangrene. Pathophysiologically, gangrene is most likely related to small-vessel occlusion. Skin necrosis and gangrene in association with RMSF are the extreme end on a continuum from reversible to irreversible skin and tissue damage caused by Rickettsia rickettsii. Most patients with RMSF have a typical skin rash that resolves without sequelae. Some patients develop minute cicatrices marking the location of focal cutaneous necrosis; for other patients, digital ischemia occurs transiently or evolves to produce severe ischemic changes without gangrene that result in permanent impairment. At the far end of this clinical continuum are patients who develop gangrene requiring amputation. PMID- 8507754 TI - Wound botulism in a patient with a tooth abscess: case report and review. AB - We describe a case of wound botulism associated with a tooth abscess in a 5-year old boy. We reviewed the literature and reports to the Centers for Disease Control and Prevention (Atlanta) of laboratory-confirmed cases of wound botulism. From 1943 through 1990, 47 cases were reported. Type A botulinus toxin was identified in 32 cases, type B in 13, types A and B in 1, and an unknown type in 1. Botulism was associated with wounds from trauma, use of injectable drugs, and surgery. Sinusitis after use of intranasal cocaine has also been associated with botulism. Treatment for wound botulism includes prompt debridement of the wound for eliminating anaerobic conditions, intensive care, and treatment with antitoxin. PMID- 8507756 TI - Pharmacokinetics of new oral cephalosporins, including a new carbacephem. AB - This review analyzes the pharmacokinetics of new oral cephalosporins, including esters, non-esters, and the carbacephem loracarbef, in healthy volunteers, as described in the literature and evaluated in several studies of our own. Single dose studies have demonstrated considerable pharmacokinetic differences among these compounds. Cefixime, cefpodoxime proxetil, and cefetamet pivoxil are characterized by a low peak concentration and a prolonged half-life, while the other new agents have higher peak levels and shorter half-lives. Except for cefixime, the new oral cephalosporins are eliminated mainly by the kidneys. Pharmacokinetic studies in the elderly and in children indicate that the bioavailability of these agents is not influenced by age. Food increases the bioavailability of the ester cephalosporins but does not affect the absorption kinetics of the other new drugs. PMID- 8507755 TI - Infection due to Rhizomucor pusillus: report of four cases in patients with leukemia and review. AB - Rhizomucor pusillus, a thermophilic fungus of the order Mucorales, is a rare cause of human infection. A search of the literature has produced only seven reports describing nine cases of infection caused by this organism. Recently, over a period of 17 months, four cases of R. pusillus infection in patients with leukemia were diagnosed: a cluster of three cases in a Montreal hospital and one isolated case from Quebec City. All four cases were proven both by histopathologic examination and by culture of tissues. In three cases, pulmonary involvement was confirmed following lung surgery, and in one case, disseminated infection was observed at autopsy. All patients received amphotericin B, and two underwent surgical debridement; however, none of the patients survived. PMID- 8507757 TI - Value of the polymerase chain reaction for the detection of Toxoplasma gondii in cerebrospinal fluid from patients with AIDS. AB - To investigate whether the polymerase chain reaction (PCR) on the BI gene of Toxoplasma gondii could contribute to the diagnosis of cerebral toxoplasmosis in patients with AIDS, we retrospectively tested CSF samples from 20 patients with AIDS suspected of having cerebral toxoplasmosis for the presence of T. gondii. Suspicion of cerebral toxoplasmosis was based on accepted criteria. Nine patients with AIDS with IgG antibodies to T. gondii but who were not suspected of having cerebral toxoplasmosis and four patients with AIDS seronegative for T. gondii served as negative control patients. T. gondii was demonstrated by PCR in the CSF from 13 of the 20 patients with AIDS suspected of having cerebral toxoplasmosis but was not demonstrated in the CSF samples from the nine control patients seropositive for T. gondii and the four control patients seronegative for T. gondii. The data were statistically evaluated. This study shows the value of PCR for the detection of T. gondii in CSF for the diagnosis of cerebral toxoplasmosis in patients with AIDS. PMID- 8507758 TI - Native-valve endocarditis due to Neisseria sicca: case report and review. AB - Many species of the Neisseria, gram-negative diplococci that are frequent respiratory commensals in humans, have been regarded as being nonpathogenic or as causing disease in only immunocompromised hosts; in contrast, gram-negative diplococci such as Neisseria meningitidis and Neisseria gonorrhoeae are known pathogens. We report a case in which Neisseria sicca was the cause of serious infection (with catastrophic consequences) in an immunocompetent patient and review the world literature on endocarditis due to N. sicca. PMID- 8507759 TI - Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis. AB - This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987). In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks. During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks. Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy. No significant differences were observed between monotherapeutic regimens and those including rifampicin. PMID- 8507760 TI - Fungal infections in solid-organ transplantation. AB - Fungal infections following solid-organ transplantation remain a major cause of morbidity and death. Their incidence ranges from 5% among recipients of kidney transplants to as high as 40% among recipients of liver transplants. Species of Candida and Aspergillus account for more than 80% of fungal episodes. Moreover, more than 80% of fungal infections occur within the first 2 months after transplantation, with a resulting mortality of 30%-100%. The pathogenesis of infection and the risk factors involved depend on the type of transplant and the infecting microorganism. Cyclosporine has not significantly reduced the incidence or severity of fungal infections in this population. The value of surveillance cultures and fungal antigen detection in solid-organ transplant recipients remains to be determined. Amphotericin B is still a first-line drug, but its potential nephrotoxicity makes its use problematic, especially in renal transplant recipients. Fluconazole is a potential alternative for the treatment of infections due to Candida species and Cryptococcus neoformans. The role of antifungal compounds in the prophylaxis of fungal infection in recipients of solid-organ transplants needs to be established. PMID- 8507761 TI - Brainstem encephalitis (rhombencephalitis) due to Listeria monocytogenes: case report and review. AB - Listerial brainstem encephalitis is a rare disease. Only 62 cases have been reported previously; all were in adults, only 8% of whom were immunosuppressed. The disease has a characteristic biphasic course: a nonspecific prodrome of headache, nausea or vomiting, and fever lasting for several days is followed by progressive asymmetrical cranial-nerve palsies, cerebellar signs, hemiparesis or hypesthesia, and impairment of consciousness. Neck stiffness was initially present in only 55% of the cases described thus far. Studies of cerebrospinal fluid often revealed only mild abnormalities. Cultures of cerebrospinal fluid and blood were positive in 41% and 61% of cases, respectively. Respiratory failure occurred in 41% of cases. Initial computed tomography of the brain often gave normal results; magnetic resonance imaging better demonstrated brainstem abnormalities. Overall mortality was 51%. All untreated patients died. When treatment with ampicillin or penicillin was initiated early, the rate of survival was > 70%; however, neurological sequelae developed in 61% of survivors. PMID- 8507762 TI - Tension pneumocephalus: acute neurological deterioration associated with pleocytosis of the CSF. AB - Tension pneumocephalus is an uncommon condition characterized by dramatic neurological deterioration and massive accumulations of intracranial air. Inflammatory changes in the CSF may mimic an infectious process. In this report we describe a case of tension pneumocephalus in which the patient presented with pleocytosis of the CSF. PMID- 8507763 TI - Bacteremia due to Pseudomonas aeruginosa in children with AIDS. AB - Six episodes of Pseudomonas aeruginosa bacteremia in five children with AIDS were reviewed to characterize further the disease caused by this pathogen. Hypotension occurred in five episodes, and two children died. Bacteremia was associated most frequently with new pulmonary infiltrates and skin lesions, but additional sites of infection were also observed (the middle ear, an abdominal abscess, and the CNS). None of the children had catheter-associated infection, and only three were neutropenic. P. aeruginosa should be considered as a cause of sepsis in children with AIDS. PMID- 8507764 TI - Sex difference in chronic hepatitis B virus infection: studies of serum HBeAg and alanine aminotransferase levels in 10,431 asymptomatic Chinese HBsAg carriers. AB - To study the difference between the sexes with regard to chronic hepatitis B virus infection, we surveyed levels of serum hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) among 10,431 asymptomatic Chinese carriers of hepatitis B surface antigen (HBsAg) in Taiwan. There were 7,095 men and 3,336 women in this study; ages ranged from 15 to 70 years. HBeAg was detected in 19.6% of HBsAg carriers. The prevalence of HBeAg decreased significantly with increasing age. HBeAg was detected in 17.7% of men and 23.6% of women. After correction for the confounding effect of age, it was found that the prevalence of HBeAg was significantly higher among women than among men. The level of serum ALT was abnormal in 20.8% of HBsAg carriers. Abnormal ALT levels were significantly more frequent among HBsAg carriers who tested positive for HBeAg (39.7%) than among those who did not (16.2%; P < .001). Among the HBeAg-positive carriers, 43.2% of men and 34.2% of women had abnormal ALT levels, and men were 1.45 times more likely to have abnormal ALT levels than women (P < .001). Among the carriers who were negative for HBeAg, 20.6% of men and only 6.0% of women had abnormal ALT levels, and men were 3.98 times more likely to have abnormal ALT levels than women (P < .001). Overall, 24.6% of men and only 12.6% of women had abnormal ALT levels, and men were 2.33 times more likely to have abnormal ALT levels than were women (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507765 TI - Neonatal sepsis and meningitis in Mallorca, Spain, 1977-1991. AB - In a retrospective study at Son Dureta Hospital (Palma de Mallorca, Mallorca, Spain) of the period 1977-1991, 334 cases of culture-proven sepsis and/or meningitis in neonates born at the facility were identified. Overall, there was an incidence rate of 4.9 cases per 1,000 live births. The case-fatality rate was 7.5%. Infection was more frequent in infants of low birth weight, with the exception of infants with meningitis and infections due to group B Streptococcus and Listeria species. The patterns of predominance among bacterial pathogens that were isolated changed during the period studied. From 1977 to 1984, Klebsiella pneumoniae was the most frequent such isolate, but this frequency declined in the following years. Group B Streptococcus organisms and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and late-onset infections, respectively. The frequency with which other pathogens were isolated did not vary significantly during the study period. Invasive infection caused by Candida organisms was found in two patients. The incidence of infection due to group B streptococci has increased in the last few years (to 2.4 cases per 1,000 live births in 1991) and has become a significant problem that requires a thorough epidemiological evaluation. PMID- 8507766 TI - Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin. PMID- 8507767 TI - Tuberculous chest wall abscess in patients with AIDS. PMID- 8507768 TI - Spontaneous pneumococcal peritonitis in young women. PMID- 8507769 TI - Acute pancreatitis associated with the administration of meglumine antimonate for the treatment of visceral leishmaniasis. PMID- 8507770 TI - Amyloidosis and infection due to human immunodeficiency virus. PMID- 8507771 TI - Aspergillus fumigatus pneumonia in neutropenic patients during therapy with fluconazole for infection due to Candida species. PMID- 8507772 TI - Bacteremia due to CDC group II pink coccoid bacilli. PMID- 8507773 TI - Duplicate submission and publication of correspondence. PMID- 8507774 TI - Laminated three-dimensional biodegradable foams for use in tissue engineering. AB - A novel processing technique is reported to construct three-dimensional biodegradable polymer foams with precise anatomical shapes. The technique involved the lamination of highly-porous membranes of porosities up to 90%. Implants with specific shapes were prepared made of poly(L-lactic acid) and copolymers of poly(DL-lactic-co-glycolic acid) to evaluate feasibility. The biomaterials produced have pore morphologies similar to those of the constituent membranes. The pores of adjacent layers of laminated devices are interconnected, resulting in continuous pore structures. The compressive creep behaviour of multilayered devices is also similar to that of the individual layers. Recent discoveries from our group and others that organs and tissues can be regenerated and reconstructed, using cells cultured on synthetic biodegradable polymers, renders this method useful in creating polymer-cell graft for use in cell transplantation. PMID- 8507775 TI - Ion concentration effects on bone streaming potentials and zeta potentials. AB - Electrical potentials are dependent on the properties of the solid and fluid phases of bone. The solid phase in bone is composed of an organic matrix and inorganic bone mineral fibre, while the fluid phase is separated into compartments associated with the vascular channel system and mineralized matrix. Recently, a piezoelectric and electrokinetic response following mechanical deformation was demonstrated in fully hydrated bone. However, alterations in the fluid phase and the effects on streaming potentials where flow through the sample due to pressure on the fluid phase without prior solid matrix mechanical deformation have not been examined. Streaming potentials in high ionic strength solutions reveal a flow-dependent streaming potential in the absence of mechanical deformation not previously observed in stress-generated potentials. Streaming potentials in high ionic strength sodium chloride solutions (0.75 M) of control and deproteinized samples suggest that organic molecules and ions in the electrical double layer may be susceptible to flow-induced alterations which can modify the streaming potentials generated. Alterations in properties of the fluid phase can modify the streaming and zeta potentials and may play a role in the biofeedback response to bone tissue. PMID- 8507776 TI - Comparison of mechanical properties of human, bovine bone and a new processed bone xenograft. AB - The study compared the mechanical properties of human bone, fresh bovine bone and a new highly purified bone xenograft: T650 (Lubboc-Laddec). Destructive, compressive tests were performed to determine Young's modulus and ultimate strength, with a constant deformation rate of 0.025 mm min-1. The stress-strain curves obtained from all the non-human specimens especially the T650, did not differ significantly from those observed with human bone. Human and fresh bovine samples presented a significantly different Young's modulus. The T650 samples, depending upon their trabecular texture (dense or medium) also differed significantly from each other (132.9 +/- 52.3 versus 80.0 +/- 37.3 MPa, P < 0.05). Their moduli were similar to those of bovine and human cancellous bone, respectively (117.49 +/- 61.53 versus 77.36 +/- 54.96. P < 0.05). The ultimate strength of T650 dense (9.6 +/- 3.7 MPa) was similar to bovine (8.5 +/- 4.2 MPa) and human bone (8.78 +/- 5.2 MPa): the T650 medium (5.9 +/- 2.8 MPa) was significantly different from the other specimens. PMID- 8507777 TI - Erosion and compressive strength of hybrid glass ionomer cements when light activated or chemically set. AB - It is claimed that light-activated hybrid glass ionomer cements offer advantages over the conventional glass ionomer lining materials. The compressive strengths and erosion rates of two hybrid glass ionomer lining cements, when light activated and chemically set, were compared with conventional glass ionomer cements. The results demonstrated that the erosion rates of the light-activated materials were comparable with those of the conventional materials. The conventional material, Ketac-Bond, was stronger than the light-activated hybrids. When the hybrid materials were allowed to set chemically alone, their performance was inferior to the conventional glass ionomer lining cements. PMID- 8507778 TI - Biocompatibility and resorbability of a polylactic acid membrane for periodontal guided tissue regeneration. AB - The biocompatibility and degradation processes of biomembranes made of a mixture of a high molecular weight racemic polylactic acid (PLA50P) with 0, 10, 20 and 30% w/w racemic polylactic acid oligomers (PLA50p) were assessed for morphological changes in subcutaneous abdominal membrane implantations after 15, 21, 30 and 60 d in 45 Wistar rats. These membranes, prepared for periodontal guided tissue regeneration, showed excellent tissue tolerance without an inflammatory reaction. The higher the content in low molecular weight polylactic acid, the higher the degradation rate. At 60 d, the resorption process was almost complete. This process was initiated by outgrowths of short vascular septa, which developed into lobular networks infiltrating the membranes, which were progressively replaced by normal fibrous connective tissue. PMID- 8507779 TI - In vitro evaluation of cell/biomaterial interaction by MTT assay. AB - The tetrazolium-based colorimetric assay (MTT test) measures only in vitro living cells and the results are directly related to the number of viable cultured cells. It has been adopted in immunological investigations, cancer research and, recently, biocompatibility evaluation. We used the MTT method with minor modifications to fit it to an in vitro study of biomaterial-cell interactions. The MTT assay was confirmed to be feasible, rapid and reproducible. Moreover, it showed a good correlation with other in vitro proliferation assays, such as the 3H-thymidine uptake assay. By using the MTT method and the ASTM procedure for extracting biomaterials, we quantified the in vitro cell compatibility of different metals and polymers. PMID- 8507780 TI - Retention of thrombin by polytetrafluoroethylene: influence on the adsorption of fibrinogen/fibrin. AB - Beads of polytetrafluoroethylene were used to investigate adsorption of thrombin and the influence of the adsorbed protease on a subsequent deposition of fibrinogen. Adsorption of active thrombin was not detected by a specific fluorogenic substrate unless > 0.1 units/ml had been applied. Adsorption was considerably improved by albumin, which protected soluble thrombin from inactivation by hydrophobic surfaces. Retention of active thrombin was optimal at ca. 0.1% albumin and decreased at higher concentrations. After incubation with plasma, negligible thrombin activity was detected at the polytetrafluoroethylene beads by the fluorogenic substrate. However, repeated incubation with fresh plasma samples resulted in adsorbed activity rising with each step. This result suggested that thrombin activity should also accumulate at a polytetrafluoroethylene surface in vivo if fresh blood is permanently flowing past. Adsorbed thrombin improved the subsequent retention of fibrinogen, monitored by an antibody technique. Concomitantly, fibrinopeptides A, AP and AY were slowly released whilst fibrinopeptide B was not detectable before 24 h. PMID- 8507781 TI - Effects of metallic ions and diphosphonates on inhibition of pericardial bioprosthetic tissue calcification and associated alkaline phosphatase activity. AB - This study focused on the association of extrinsic alkaline phosphatase (AP) activity with both early and advanced calcification of glutaraldehyde-pretreated bovine pericardial bioprosthetic (GPBP) tissue, and the inhibition of both calcification and AP activity by pre-incubation in diphosphonates (sodium ethanehydroxydiphosphonate [NaEHDP], aminopropanehydroxydiphosphonate [APD]) and metallic salts (FeCl3, Ga(NO3)3, AICI3). GPBP specimens were implanted subcutaneously in 3 wk old male rats after pre-incubation. Following explantation of the tissue at 72 h and 21 d, calcification was assessed morphologically by light microscopy and chemically by atomic adsorption spectroscopy for calcium content and by molybdate complexation for phosphorus. AP activity was characterized by enzymatic hydrolysis of paranitrophenyl phosphate and by histochemical studies. In both control and pretreated groups, AP levels were greater in 72 h explants than 21 d retrievals, which demonstrated extensive calcification in control explants. All pre-incubations that resulted in inhibition of calcification after 21 d, except for APD, were associated with 72 h AP content which was lower than control specimens. The typical time of initiation of calcification was 72 h, as determined by previous studies with this model system. Covalently bound APD inhibited calcification. Increased AP activity in the APD group may be due to the toxicity of this agent with resultant acute inflammation, or other incompletely understood effects of diphosphonates on calcification and AP. Furthermore, EHDP and Ga3+ incubations were also associated with decreased GPBP AP at 72 h compared to control, but were not effective for inhibiting calcification after 21 d. We concluded that inhibition of peak GPBP AP activity is not necessarily associated with the prevention of GPBP mineralization. PMID- 8507782 TI - Quantitative in vivo assessment of the tissue response to dermal sheep collagen in abdominal wall defects. AB - We quantified the tissue response, tissue organization and patency of biodegradable patches for the repair of abdominal wall defects. We used dermal sheep collagen, cross-linked with hexamethylenediisocyanate in a model. The collagen patches were implanted either untreated or plasma polymerized with tetrafluoroethylene (TFE), to improve the properties of the patch for bowel adhesion and rate of degradation. The implants with surrounding tissue were retrieved after 3 d, 1, 2, 4, 6 and 8 wk, then sectioned and stained specifically for macrophages, neutrophils, T-lymphocytes and endothelium. Only macrophages and neutrophils were observed in the implant and surrounding tissue, with different antigen expression in the macrophages. This was found to be dependent on whether the macrophages were found within the implant or in the surrounding tissue. The neutrophils and macrophages were assessed using image analysis techniques to quantify the tissue responses to treated and untreated collagen, enabling comparison of the respective tissue responses. No significant differences were found between the two forms of this collagen. Infection played a key role in the severity of the tissue response around both types of implants, resulting in large variations in cell counts at each time period. Treating the collagen with TFE did not significantly improve its performance in this application. PMID- 8507783 TI - Adherence to a metal, polymer and composite by Staphylococcus aureus and Staphylococcus epidermidis. AB - Bacterial adherence on to several materials with a potential application in reconstructive surgery was studied. Polymer (poly(L-lactide)), composite (hydroxyapatite/poly(L-lactide)) and metal (316L stainless steel) were evaluated both as smooth and sandblasted specimens. All materials were incubated in phosphate-buffered saline, challenged with Staphylococcus aureus or S. epidermidis and evaluated for up to 24 h. S. aureus showed a preference for the metal and composite tested over the polymer used. For S. epidermidis no preference was found for one of the investigated materials. The influence of surface roughness on bacterial growth was demonstrated by increased colonization on the sandblasted specimens. PMID- 8507784 TI - Albumin grafting on to polypropylene by thermal activation. AB - 4-azido-2-nitrophenyl albumin (ANP-albumin) was prepared by reacting 4-fluoro-3 nitrophenyl azide with albumin. The thermal decomposition kinetics of phenyl azide of ANP-albumin was studied at various temperatures by Fourier-Transform Infrared (FTIR) spectroscopy. The decomposition rate of the phenyl azide increased with temperature. The activation energy for the first-order decomposition of the phenyl azide was 128.0 kJ/mol. Albumin was grafted on to polypropylene (PP) films by thermolysis of the azido groups of ANP-albumin with no premodification of the PP surface. The albumin-grafted surface was characterized by electron spectroscopy for chemical analysis (ESCA) and by quantitative determination of platelet adhesion and activation. The bulk concentration of ANP-albumin used for adsorption varied from 0.001 to 30 mg ml-1, and the albumin-adsorbed PP films were incubated at 100 degrees C for up to 7 h. The carbon and nitrogen peaks resulting from the grafted albumin were used to compare the surface albumin concentrations as a function of the concentration of ANP-albumin in the adsorption solution. When the PP film was adsorbed with ANP albumin at the concentration of 5 mg ml-1 or higher and incubated at 100 degrees C for longer than 5 h, the surface became resistant to platelet adhesion. The ANP albumin can be grafted on to chemically inert surfaces such as PP surface through simple thermolysis of azido groups to prevent platelet adhesion and activation. PMID- 8507785 TI - Biocompatibility of tetracalcium phosphate cement when used as a bone substitute. AB - We evaluated the biocompatibility of tetracalcium phosphate (4CP) cement, made of 4CP powder and 40 wt% copolymer of polyacrylic acid/itaconic acid and 10 wt% citric acid solution. Light and electron microscopic characteristics were studied 3, 10 and 30 d after implantation. Neither inflammation nor foreign-body giant cell reaction was observed in the tissue adjacent to the implanted material. After 30 d, this material was surrounded with newly formed bone. Ultrastructural examination showed that osteogenesis occurred directly on the surface of the material. These findings suggest that this 4CP cement is biocompatible and possesses osteoconductive properties. PMID- 8507786 TI - Effect of pore sizes and cholesterol-lipid solution on the fracture toughness of pure titanium sintered compacts. AB - Commercial pure titanium has been widely used as an implant material because of its excellent biocompatibility and good ductility. To determine the effect of pore size on the fracture resistance of porous titanium compacts, a series of fracture toughness (KQ) tests were performed on commercial pure titanium powder compacted to 0.17 and 0.62 GPa. Pore sizes ranged from 25 to 103 microns, with porosity between 8.5 and 35%. Two sets of fracture toughness tests using disc shaped compacts (ASTM E 399-90) were performed, the first in air at 37 degrees C and the second with compacts treated in cholesterol-lipid solution at 37 degrees C. The KQ value of compacts with a smaller mean pore size (ca. 50 microns) was approximately twice that of the compacts with a larger mean pore size (100 microns). The effect of cholesterol-lipid solution treatment was detrimental, perhaps due to preferential lipid absorption by the titanium oxide and/or the presence of chlorides. For the smaller pore size compacts, the KQ values decreased by up to 20%. For the larger pore size compacts, the effect of cholesterol-lipid solution was less significant. Morphologically, compacts with smaller pore size had a predominantly ductile fracture with significantly higher dimple density than the larger pore size compacts. PMID- 8507787 TI - Tissue response to titanium implants in experimental antigen-induced arthritis. AB - The healing of threaded, non-alloyed titanium implants in bone was studied in an experimental model of monoarticular arthritis in New Zealand white rabbits. Immunization with bovine serum albumin (BSA) and repeated intra-articular injections with BSA elicited an immune response and clinical signs of inflammation. Implants were inserted and 6 wk after surgery, with full weight bearing, the rabbits were killed by perfusion fixation. Light microscopic morphometry showed that the cartilage was thinner and the subchondral bone had a lower density in the arthritic joints compared to the control side. The titanium implants in the arthritic joints had a lesser degree of mineralized bone-implant contact and surrounding bone than the implants inserted in control joints. The present study shows that the healing of titanium implants in the rabbit knee joint is impaired in experimental immunologic arthritis. This model may be useful for the study of biomaterial-tissue interactions under pathological conditions. PMID- 8507788 TI - Osseointegration of macroporous calcium phosphate ceramics having a different chemical composition. AB - Calcium phosphate macroporous ceramics are biocompatible for bone surgery. Their osseointegration is, however, sometimes very poor. To measure the effect of the calcium phosphate content of the ceramic on its osseointegration, macroporous ceramics, differing in their chemical composition, were implanted into sheep femurs. The ceramics were composed of different percentages of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP). All other characteristics were the same. Results were assessed histologically with image analysis and showed significant differences in the amount of bone formed at the contact of the different ceramics. Ceramics containing beta-TCP induced better osseointegration than pure HA ceramics. PMID- 8507789 TI - Polyphosphazenes as biomaterials: surface modification of poly(bis(trifluoroethoxy)phosphazene) with polyethylene glycols. AB - Investigations were carried out on the metathetical exchange reaction between the -O-CH2CF3 moieties of poly(bis(trifluoroethoxy)phosphazene) (PTFP), in the state of slightly swollen films, and the alkoxide ions derived from methoxypolyethylene glycol (MPEG) of molecular mass ranging from 350 to 5000 g/mol. The substitution of these hydrophilic chains, mostly confined to thin surface layers, was revealed by means of optical microscopy and scanning electron microscopy observations, surface elemental analysis by energy-dispersive X-ray analysis (EDXA), FTIR-ATR analysis and water contact angle measurements. The surface biocompatibility was enhanced in all cases, whilst the mechanical properties of the original PTFP films were substantially retained in the modified samples exhibiting low substitutions. Such samples were obtained especially when the metathetical reaction was carried out with MPEG5000. PMID- 8507790 TI - Thermal behaviour of hydroxyapatite intended for medical applications. AB - Four commercial hydroxyapatites (both natural and synthetic) were tested to assess transformations of the chemical and crystalline structure following variation of temperature from 20 to 1600 degrees C. The thermal behaviour of hydroxyapatite is relevant for biomedical applications such as plasma spraying of metallic implants. Thermogravimetric analysis showed a weight loss from each hydroxyapatite specimen, due to a release of structural H2O molecules; all the specimens up to 1300 degrees C were made of crystalline hydroxyapatite, determined by X-ray diffraction; at 1470 degrees C they were made of both hydroxyapatite and calcium phosphate, but at 1570 degrees C of calcium phosphate exclusively. The diffractograms of the hydroxyapatite coatings showed the same peaks as the original powders, so at the chosen plasma-spray procedure level no new phases were formed. The peak height was nevertheless lower in the plasma sprayed hydroxyapatites for all interplanar spacing values, which indicated a lower degree of crystallinity, associated with a random structure derived from an alteration to the original crystalline network. PMID- 8507791 TI - Polyurethane surface modification by graft polymerization of acrylamide for reduced protein adsorption and platelet adhesion. AB - Surface modification of polyurethane by glow-discharge treatment and subsequent graft polymerization of acrylamide was studied. The modified hydrophilic surfaces were characterized by the measurements of dynamic contact angle and zeta potentials and examined for protein adsorption behaviour and platelet adhesion. Data from in vitro and ex vivo experiments indicated a reduction of protein adsorption and platelet adhesion for the hydrophillic graft polymers, the extent of which was correlated to polymer graft density. PMID- 8507792 TI - Effect of hand segment chemistry and strain on the stability of polyurethanes: in vivo biostability. AB - We investigated four polyurethanes that were synthesized with different hard segments and four commercial polyurethanes for in vivo biostability. The four polyurethanes with the varying hard segments were based on a 3:2:1 mole ratio of methylene diphenylene diisocyanate (MDI) or methylene dicyclohexane diisocyanate (H12MDI), butanediol (BD) or ethylene diamine (ED) and polytetramethylene oxide (PTMO) (MW = 1000). Four commercial polyurethanes were also used: Biomer, Pellethane, Medtronic experimental C-19 (C-19) and Medtronic experimental C-36 (C 36). Films of the polymers were implanted subcutaneously in rats for up to 12 wk to assess their biostability. Polymer films were implanted either with a 100% strain applied or in the unstrained state. Measurement of tensile properties, molecular weight and surface properties before and after implantation assessed the stability of each of the polymers. Surface cracking was observed with scanning electron microscopy and the extent and depth of cracking were determined. Pellethane, C-19 and C-36 showed the least evidence of degradation, although all underwent strain-induced phenomena that decreased their tensile elongation when an external force was applied. After implantation, the BD chain extended polymers retained their tensile properties better than ED chain-extended polymers. H12MDI-based polyurethanes were more susceptible to surface cracking and molecular weight changes than MDI-based polyurethanes, possibly due to the lack of a crystallizable hard segment. PMID- 8507793 TI - Biodeterioration of medical-grade silicone rubber used for voice prostheses: a SEM study. AB - Silicone voice prostheses used for rehabilitation of speech after total laryngectomy are inserted in an non-sterile habitat. Deposits on explanted Groningen Button voice prostheses revealed a biofilm, due to heavy colonization of the silicone surface by bacteria and yeasts. Furthermore, it was demonstrated by scanning electron microscopy on sectioned explants that the silicone material was deteriorated by filamentous and vegetative yeast cells. The different explants showed a variety of sharp-edged, discrete yeast colonies. The yeasts grew just under the silicone surface and up to 700 microns into the silicone material. Finally, nine different types of defects in the silicone material created by the yeasts are described. This deterioration of the silicone by yeasts seems to be the main reason for the failure and the frequent replacement of the prostheses. The mechanisms of silicone deterioration are still hypothetical. PMID- 8507794 TI - Surface morphology and friction coefficient of various types of Foley catheter. AB - Urinary catheters are commonly used in chronic care facilities and geriatric homes. Problems associated with the catheters include encrustation, infection, physical trauma and inflammation. Many of these problems can be correlated to the catheter surface. Previous studies have dealt with problems associated with surface morphology and catheter composition and numerous catheter coatings have been developed to alter the surface including siliconized, Teflon and polyurethane hydrogel coatings. The hydrogel coating appears best, as it imparts a smooth, soft surface layer with lubricating properties. The paper describes a new poly(vinyl alcohol) hydrogel coating and compares its surface morphology and lubricity with other catheter coatings. Each catheter coating-type was examined by scanning electron microscopy for surface morphology. The new hydrogel coating was found to be smooth with no evidence of cracking. The apparent friction coefficient was used as an indication of surface lubricity. Friction measurement tests of the new hydrogen coating were run underwater and the friction coefficient was determined between the hydrated catheter surface and the hydrogel surface. The new hydrogel coating was found to have a high degree of lubricity in its hydrated state. PMID- 8507795 TI - Biodegradation and brain tissue reaction to poly(D,L-lactide-co-glycolide) microspheres. AB - The therapeutic application of neuroactive molecules in neuroscience is limited, due to the problems posed by the administration of these drugs (peripheral metabolism, systemic effect and passage of the blood-brain barrier). One solution is the implantation in the brain of biodegradable polymer devices with controlled release of a neuroactive drug. The biodegradation and tissue reaction of the copolymer poly(D,L-lactide-co-glycolide) microspheres prepared by the solvent evaporation method, radiosterilized and stereotactically implanted in the rat brain were studied by routine staining, immunohistochemistry and transmission electronic microscopy. The brain tissue reaction observed was a non-specific astrocytic proliferation and a macrophagous-microglial cell reaction, typically found following damage to the central nervous system. Some foreign-body giant cells were observed and the inflammatory and macrophagous reaction decreased dramatically after 1 month and almost ended after 2 months when the microspheres were totally biodegraded. The copolymer poly(D,L-lactide-co-glycolide) microspheres may be considered biocompatible to the brain tissue. PMID- 8507796 TI - [XX Meeting of the Spanish Society of Internal Medicine. Proceeding. Madrid, 3-5 June 1993]. PMID- 8507797 TI - [Growth hormone and human aging]. PMID- 8507798 TI - [Mitochondrial myopathies]. PMID- 8507799 TI - [Leishmania infection and AIDS]. PMID- 8507800 TI - [Clinical repercussions of beta-lactamases]. PMID- 8507801 TI - [Retrovirus and autoimmunity]. PMID- 8507802 TI - [Role of Helicobacter pylori in peptic ulcers]. PMID- 8507803 TI - [Ambulatory treatment of chronic respiratory insufficiency]. PMID- 8507804 TI - Computer-based analysis of continuous non-invasive blood pressure and heart rate variability-methodology and normal values during wakefulness and sleep. AB - Polysomnographic recordings were made in 10 healthy male adult subjects (mean age 25.1 +/- 2.8 years). Parameters were obtained from continuous non-invasive measurement of blood pressure and from heart rate spectra analysed both in the waking state and during sleep (stage 4). The total heart rate variability (mean +/- SE) was not significantly diminished (p < 0.2; paired t-test) during stage 4 sleep (6.2 +/- 0.5%) as compared with the waking state (7.1 +/- 0.5%). The relative heart rate variability coefficient within the frequency band HRV-II ((3 9)/min) was, however, significantly higher (p < 0.001) during slow-wave sleep (0.55 +/- 0.04) than during wakefulness (0.34 +/- 0.04). This fact is in accordance with results concerning an estimated value of the baroreflex sensitivity, which was also significantly higher (p < 0.001) during sleep stage 4 (7.0 +/- 0.8 ms/mmHg vs. 10.4 +/- 1.4 mmHg). PMID- 8507805 TI - [Algorithm for calibrating eye movements]. AB - A mathematical model and the corresponding computer program based on an algorithm for calibration of eye movements are described. The latter is used to represent and analyse eye movements on a monitor screen using the EYE/HAND software, with the aid of which movements of eye and hand can be represented either simultaneously or separately. Demands on the rate of data acquisition and representation of the curves (real-time monitoring) are satisfied. Calibration is based on vector transformation of the digitised analog values to monitor coordinates. The parameters of the transformation algorithm are determined by fixation of the eye movements to freely selectable monitor screen markers. PMID- 8507806 TI - Towards automated sleep classification in infants using symbolic and subsymbolic approaches. AB - The paper addresses the problem of automatic sleep classification. A special effort is made to find a method of extracting reasonable descriptions of the individual sleep stages from sample measurements of EGG, EMG, EOG, etc., and from a classification of these measurements provided by an expert. The method should satisfy three requirements: classification accuracy, interpretability of the results, and the ability to select the relevant and discard the irrelevant variables. The solution suggested in this paper consists of a combination of the subsymbolic algorithm LVQ with the symbolic decision tree generator ID3. Results demonstrating the feasibility and utility of our approach are also presented. PMID- 8507807 TI - [Magnetic resonance tomography in data collection in biomechanics]. AB - Invasive measurement of internal loads is either not possible at all, or is extremely difficult. A non-invasive method for use in the clinical setting might be the computer-aided simulation of a mechanical model. All the geometrical data required can be obtained, at a level of accuracy not previously attainable, with the aid of magnetic resonance imaging. PMID- 8507808 TI - Angiotensin II as a renal growth factor. AB - Angiotensin II (ANG II) can have multiple effects on the kidney, including influences on the regulation of glomerular hemodynamics and tubular transport as well as consequences for the glomerular processing of macromolecules. The recognized suppressive effects of angiotensin-converting enzyme inhibitors on compensatory renal growth, even in the absence of hemodynamic effects, and the well-documented proliferative effect of ANG II on vascular smooth muscle cells have provided the background for the recent intensive interest in this peptide as a renal cytokine. Diverse cell types along the nephron express a variety of ANG II receptors. These receptors and their putative signal transduction pathways have been best characterized in mesangial and proximal tubular cells. Culture experiments provide convincing evidence that ANG II can be a phenotypic influence on these cell types. The growth responses and the associated signal transduction pathways, however, are different in mesangial and proximal tubular cells. These ANG II-mediated responses are also associated with an increase in the synthesis of distinct collagen subtypes, potentially linking the growth stimulatory effects of ANG II to the irreversible changes of glomerulosclerosis and tubulointerstitial fibrosis observed in chronic renal failure. Preventing the intrarenal actions of ANG II with angiotensin-converting enzyme inhibitors or with the new, orally active, selective ANG II receptor antagonists may provide a rational therapeutic approach to attenuate the progression of a variety of kidney diseases. PMID- 8507809 TI - Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review. AB - Infectious diseases remain among the most morbid events and are an important cause of death in ESRD. These events are related to an acquired immunodeficiency that progresses during the development of uremic retention, as part of the broader spectrum, displayed by the "uremic syndrome". A central role in the hose defense against bacterial infection is played by the phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest bacteria (phagocytosis), which is followed by the destruction of those bacteria (killing capacity). This article reviews the mechanisms of development and the potential causes that have been held responsible for this aspect of the defective immune function. The observed changes are attributed to alterations in receptor expression, although more convincing evidence points in the direction of metabolic functional disturbances, especially in the NAD(P)H-oxidase-dependent production of oxygen free radicals. The most important causative factors are: uremic toxicity, iron overload, renal anemia, dialyzer bioincompatibility, and the type of renal replacement therapy. It is concluded that the phagocytic defect in ESRD is multifactorial and that each factor should be managed by specific therapeutic approaches. PMID- 8507810 TI - The kidney in sarcoidosis. AB - Sarcoidosis has been associated with a wide spectrum of renal manifestations, including disordered calcium metabolism, nephrocalcinosis, nephrolithiasis, granulomatous interstitial nephritis, and glomerulonephritis. In some patients, two or more manifestations of renal sarcoidosis may coexist. The case of a young patient with sarcoidosis who presented with hypercalcemia and acute renal failure is discussed. Despite normalization of the serum calcium with intravenous fluids and corticosteroids, his renal insufficiency persisted. A diagnostic renal biopsy was performed to determine the etiology of his renal failure and was helpful in the selection of optimal medical therapy. PMID- 8507811 TI - Bradykinin generation by dialysis membranes: possible role in anaphylactic reaction. AB - Several recent reports have described a high incidence of anaphylactic reactions in patients being dialyzed with high-flux membranes while simultaneously using angiotensin-converting enzyme inhibitors. Many of these reports implicate polyacrylonitrile (PAN) as the membrane commonly involved in these reactions. To elucidate potential mechanisms of these anaphylactic reactions, whether dialysis membranes can activate the Hageman factor-dependent (contact) pathways as assessed by the in vitro generation of activated Hageman factor (Hfa), as well as the formation of kallikrein and subsequent bradykinin generation was examined. Both cuprophane (CUP) and PAN membranes were able to activate Hageman factor and convert prekallikrein to kallikrein as measured by an ELISA against kallikrein-C1 inactivator complexes. Subsequently, the active kallikrein was able to cleave bradykinin from its endogenous substrate, high-molecular-weight kininogen. However, it was found that the PAN membrane consistently led to an earlier and significantly higher formation of Hfa and kallikrein when compared with CUP. Importantly, there was also a pronounced but transient generation of bradykinin by the PAN membrane, in contrast to slower bradykinin formation by CUP, with both normal and uremic blood. It was proposed that the early and vigorous bradykinin generation induced by the contact of blood with PAN could explain, in part, the pathogenesis of the reported anaphylactoid reactions. PMID- 8507812 TI - Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients. AB - It was found that two known renal vasodilators had different effects on RBF and GFR in the setting of therapeutic blood levels of cyclosporine in hypertensive renal transplant patients. Captopril lowered blood pressure in these patients but also lowered blood flow and GFR. Nifedipine lowered blood pressure to the same degree but without lowering either RBF or GFR. PMID- 8507813 TI - Angiotensin-converting enzyme inhibitor fetopathy. AB - Angiotensin-converting enzyme (ACE) inhibitors are widely used for controlling hypertension. Their use in women who are pregnant is not without risk to the fetus. We describe three infants exposed in utero to ACE inhibitors who had adverse outcomes. These cases, combined with other reports in the literature, suggest strongly that these drugs are fetotoxic. ACE inhibitor fetopathy is characterized by fetal hypotension, anuria-oligohydramnios, growth restriction, pulmonary hypoplasia, renal tubular dysplasia, and hypocalvaria. Although the true frequency of adverse fetal effects has yet to be determined, because of the debilitating and lethal nature of the fetal damage when it occurs, it is our recommendation that ACE inhibitors not be used in pregnancy, particularly in the second and third trimesters. PMID- 8507814 TI - Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys. AB - Erythropoietin (EPO)-induced hypertension is a common complication of EPO usage. The hypothesis that erythropoietin is antinatriuretic and that the sodium retention is mediated by intrarenal angiotensin II production was tested. Experiments were performed in Wistar rat kidneys perfused for 60 min in an isolated system. A dose-response curve was performed for EPO at 0, 10, 100, 1,000, and 10,000 mU/mL. EPO administration resulted in a dose-dependent decrease in sodium excretion to a maximum of 50% at the 1,000 mU/mL dose. In a second experiment, kidneys from five groups were perfused: controls, EPO (100 mU/mL), captopril (50 ng/mL), captopril (50 ng/mL) plus EPO (100 mU/mL), and the angiotensin receptor antagonist losartan (1 nM) plus EPO (100 mU/mL). The administration of EPO resulted in an immediate decrease in average sodium excretion (30%) with no change in GFR or other renal function parameters. Pretreatment with captopril or losartan blocked the effect of EPO. Captopril alone had no effect on renal function. A final experiment demonstrated the ability of losartan (10 nM) to block the pressor effects of angiotensin II (0.01, 0.1, and 1 nM). It was concluded that EPO acts within the kidney to cause the production of angiotensin II, which mediates the increased reabsorption of sodium. PMID- 8507815 TI - Involvement of tubular sodium in the formation of dopamine in the human renal cortex. AB - This study has examined the influence of sodium (0, 20, 40, 80, 120, and 160 mM) and ouabain (100, 500, and 1,000 microM), an inhibitor of the enzyme Na(+)-K+ ATPase, on the synthesis of dopamine in slices of human renal cortex loaded with exogenous L-dihydroxyphenylalanine (L-DOPA). The deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The formation of dopamine and its deamination to DOPAC in slices and homogenates of human renal cortex closely depended on the concentration of L-DOPA added to the medium; in homogenates of renal cortex, the production of dopamine was found to be 74% of that occurring in the renal medulla. Decarboxylation of L-DOPA was found saturable at 1,000 microM L-DOPA, which had Vmax and Km values for L-amino acid decarboxylase activity of, respectively, 5.8 +/- 0.6 nmol/mg of protein per hour and 62 +/- 8 microM. The accumulation of newly formed dopamine and DOPAC in kidney slices loaded with L-DOPA (50 and 100 microM) was found to be partially dependent on the concentration of sodium in the medium; at 0 mM sodium, the synthesis of dopamine from L-DOPA was found to be half of that occurring at 160 mM sodium. A similar picture could be observed for DOPAC. The fractional rate of accumulation (k; mM sodium-1) at 50 and 100 microM L-DOPA was, respectively, 0.0016 +/- 0.0002 and 0.0016 +/- 0.0005 for dopamine and 0.0018 +/- 0.0002 and 0.0021 +/- 0.0005 for DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507816 TI - Hyponatremia induced by vasopressin or desmopressin in female and male rats. AB - Previous studies have demonstrated that hyponatremia induced by continuous sc infusion of desmopressin (dDAVP) in combination with a liquid diet allows brain volume adaptation with negligible morbidity and mortality in rats. In contrast, some studies of hyponatremia induced by injections of long-acting preparations of arginine vasopressin (AVP) have reported mortality rates as high as 20 to 80%. To evaluate the possibility that the use of AVP to produce antidiuresis may cause greater mortality as a result of increased brain edema, this study examined brain water and electrolyte contents of male and female rats after varying periods of hyponatremia induced by continuous sc infusions of either dDAVP (5 ng/h) or AVP (100 ng/h). Rats infused with AVP had AVP levels in plasma elevated into ranges reported in patients with the syndrome of inappropriate antidiuretic hormone secretion (17.5 +/- 2.0 pg/mL); however, despite the production of comparably severe degrees of hyponatremia with both AVP and dDAVP infusions (105 to 115 mmol/L), no mortality occurred in any of the rats (N = 40 AVP infused and N = 40 dDAVP infused). AVP- and dDAVP-induced hyponatremia both caused transient brain edema in female and male rats, but brain water content returned to the levels of normonatremic controls after 5 days in the females and 10 days in the males. However, at no time during the 10-day study period did brain water content differ significantly between rats infused with AVP or dDAVP, either in females or males. Decreases in brain electrolytes were also equivalent in the AVP- and dDAVP infused male and female rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507817 TI - Hormonal modulation of ionic permeability in human red blood cells. AB - It has previously been reported that both exogenous adenosine cAMP analogs and forskolin-induced elevations in intracellular cAMP concentrations selective increase relative ionic chloride permeability in normal human red blood cells (RBC). A similar selectively increase in relative ionic chloride permeability was observed in untreated uremic subjects in whom endogenous RBC cAMP concentrations are chronically elevated. To detect which hormones might modulate RBC cAMP and ionic permeabilities, RBC were exposed to norepinephrine, epinephrine, and parathyroid hormone. Thereafter, RBC cAMP concentrations were measured by RIA and relative ionic permeabilities were determined in human RBC ghosts with the potential sensitive fluorescent probe diS-C3-(5). In ghosts prepared from normal RBC, norepinephrine and epinephrine significantly increased intracellular cAMP concentrations; in these ghosts, relative ionic chloride permeability (permeability of chloride/permeability of potassium (PCI/PK)), but not PNa/PK (permeability of sodium/permeability of potassium), was significantly increased. In contrast, exposure to parathyroid hormone did not affect either cAMP concentrations or relative ionic permeabilities. These results are consistent with the presence of adrenergic receptors and the absence of parathyroid hormone receptors in RBC. These studies demonstrate that hormonally induced changes in cAMP can modulate RBC relative ionic chloride permeability and suggest that, in uremic RBC, increased relative ionic chloride permeability could be consequent to elevated plasma levels of epinephrine or norepinephrine. PMID- 8507818 TI - Predictors of mortality in hemodialysis patients. AB - Serum biochemical measures suggestive of undernutrition have been reported to correlate with 1-yr mortality risk in prevalent groups of hemodialysis patients. The predictive power of these variables has not been reported in newly diagnosed patients or in patients whose dialysis prescription is guided by urea kinetics. The relationship of these predictors to mortality over periods of longer than 1 yr is also unreported. Therefore, the survival of 184 hemodialysis patients was examined for up to 44 months (1987 to 1991) with the Cox proportional hazards model. Baseline demographic, clinical, and biochemical parameters were used as independent variables. To adjust for bias in patient selection, the survival of patients with 12 months or less of prior dialysis at the time of enrollment ("new cases") was analyzed separately from that of patients with more than 1 yr of prior treatment ("long-standing cases"). Serum albumin was less than 3.5 g/dL in 31% of new cases and in 12% of long-standing cases. Adjusting for the other variables, low serum albumin was the strongest mortality risk predictor in both new and long-standing cases. Low serum cholesterol was an independent risk predictor in both groups. Diabetes and race were not significant predictors. Mean age at enrollment was nearly a decade higher for nonsurvivors than for survivors, in both new and long-standing groups. Yet, age was not an independent risk predictor in the Cox model for the new group because of an unexpectedly high death rate among young black men. Female gender, which was confounded by increased age, took the place of age in the model for the new group. For each model, there was good agreement between observed and predicted mortality for up to 24 months. To assess the influence of dialysis treatment time and dose (measured as pre-to-post treatment urea ratio) on risk, survival was examined in a subset of 139 patients monitored for up to 22 months, from 1989 to 1991, a period when the urea ratio was used routinely. Adjusting for the other variables, low serum albumin and cholesterol again independently increased risk. The urea ratio was also a significant independent predictor. The pattern of mortality by urea ratio was U shaped, with minimum risk for values between 2.5 and 3.4 Treatment time did not influence risk. It was concluded that baseline serum values of albumin and cholesterol strongly influence survival for up to 2 yr in new and long-standing hemodialysis patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8507819 TI - Advance directives are associated with "good deaths" in chronic dialysis patients. AB - The effect of prior advance directives (AD) on the outcome when chronic dialysis patients died was evaluated in a retrospective review of consecutive deaths over a period of more than 6 yr in a large academic dialysis center. Among 182 patients who died during the period under review, 74 (41%) had previously stated their AD verbally or in writing and the prevalence of AD was highest among patients with age-related or chronically debilitating diseases. Previous statement of AD was significantly more prevalent (P < 0.001) among patients who withdrew from treatment in reconciled fashion than among patients who died suddenly and unexpectedly or who died without a reconciled decision to forego life-sustaining intervention (e.g., dialysis, intubation, emergency surgery). Further analysis shows that patients stating prior AD and patients withdrawing from treatment were most often those who made their own medical decisions ("internal" locus of decision making), rather than relying on relatives or other agents ("external" locus), and tended to be those with a definite spouse or spouse-equivalent relationship. Finally, retrospective assessment suggests that cases in which patients stated prior AD and cases in which patients withdrew from treatment were associated more frequently with a favorable outcome. It was concluded that addressing AD before a medical crisis ensues may increase the likelihood of a "good death" when complications bring the course of chronic dialysis to termination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507820 TI - Death by withdrawal from dialysis: a 20-year clinical experience. AB - The reasons for withdrawal from dialysis are not well understood. The goals of this study were to determine the risk of dying by withdrawal from dialysis over time and to elucidate pertinent clinical correlates in 716 long-term dialysis patients. These patients were monitored from the initiation of dialysis through the time of death, transplant or transfer to another program during a 20-yr period from 1970 through 1989. The causes of death in the 340 deceased patients were analyzed. Clinical correlates and associated risk factors were evaluated in the patients who died from withdrawal from dialysis. Withdrawal from dialysis was defined as: "Death with manifestations of uremia because of withdrawal from dialysis. Underlying medical conditions should not have been active, leading to rapid deterioration with imminent death." Withdrawal from dialysis and cardiac events were the second leading cause of death, each accounting for 18.5% of the deaths. Patients stopping dialysis were older at the start of dialysis than were patients dying of other causes (P < 0.0006; Kruskal-Wallis test), with 65.1% of these patients 61 yr of age and older. Cancer, malnutrition, catabolism, and "dissatisfaction with life" were important associations with the decision to withdraw. More than 50% of patients withdrawing from dialysis had either diabetic nephropathy or atherosclerotic renal vascular disease. Withdrawal from dialysis was a common cause of death in these dialysis patients especially if they were over 61 and had systemic diseases such as diabetes mellitus and renal vascular disease. The reasons for a higher incidence of withdrawal in certain programs deserve further study. PMID- 8507821 TI - Relationship between dietary protein intake and creatinine clearance. PMID- 8507822 TI - Cloning of cDNA coding for dihydroflavonol-4-reductase (DFR) and characterization of dfr expression in the corollas of Gerbera hybrida var. Regina (Compositae). AB - We are approaching corolla differentiation in Compositae by studying the regulation of flavonoid pathway genes during inflorescence development in gerbera. We have cloned a dfr cDNA from a ray floret corolla cDNA library of Gerbera hybrida var. Regina by a PCR technique based on homologies found in genes isolated from other plant species. The functionality of the clone was tested in vivo by complementing the dihydrokaempferol accumulating petunia mutant line RL01. By Southern blot analysis, G. hybrida var. Regina was shown to harbour a small family of dfr genes, one member of which was deduced to be mainly responsible for the DFR activity in corolla. Dfr expression in corolla correlates with the anthocyanin accumulation pattern: it is basipetally induced, epidermally specific and restricted to the ligular part of corolla. By comparing the dfr expression in different floret types during inflorescence development, we could see that dfr expression reflects developmental schemes of the outermost ray and trans florets, contrasted with that of the disc florets. PMID- 8507823 TI - Structure of the amplified 5-enolpyruvylshikimate-3-phosphate synthase gene in glyphosate-resistant carrot cells. AB - The structure of amplified 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) DNA of carrot suspension-cultured cell lines selected for glyphosate resistance was analyzed to determine the mechanism of gene amplification in this plant system. Southern hybridization of the amplified DNA digested with several restriction enzymes probed with a petunia EPSPS cDNA clone showed that there were differences in fragment sizes in the amplified DNA from one highly resistant cell line in comparison with the parental line. Cloning of the EPSPS gene and 5' flanking sequences was carried out and two different DNA structures were revealed. A 13 kb clone contained only one copy of the EPSPS gene while a 16 kb clone contained an inverted duplication of the gene. Southern blot analysis with a carrot DNA probe showed that only the uninverted repeated DNA structure was present in all of the cell lines during the selection process and the inverted repeat (IR) was present only in highly amplified DNA. The two structures were present in about equal amounts in the highly amplified line, TC 35G, where the EPSPS gene was amplified about 25-fold. The presence of the inverted repeat (IR) was further verified by resistance to S1 nuclease hydrolysis after denaturation and rapid renaturation, showing foldback DNA with the IR length being 9.5 kb. The junction was also sequenced. Mapping of the clones showed that the size of the amplified carrot EPSPS gene itself is about 3.5 kb. This is the first report of an IR in amplified DNA of a target enzyme gene in selected plant cells. PMID- 8507824 TI - Isolation of an Arabidopsis cDNA sequence encoding a 22 kDa calcium-binding protein (CaBP-22) related to calmodulin. AB - Complementary DNA sequences were isolated from a library of cloned Arabidopsis leaf mRNA sequences in lambda gt10 that encoded a 21.7 kDa polypeptide (CaBP-22), which shared 66% amino acid sequence identity with Arabidopsis calmodulin. The putative Ca(2+)-binding domains of CaBP-22 and calmodulin, however, were more conserved and shared 79% sequence identity. Ca2+ binding by CaBP-22, which was inferred from its amino acid sequence similarity with calmodulin, was demonstrated indirectly by Ca(2+)-induced mobility shifting of in vitro translated CaBP-22 during SDS-polyacrylamide gel electrophoresis. CaBP-22 is encoded by a ca. 0.9 kb mRNA that was detected by northern blotting of leaf poly(A)+ RNA; this mRNA was slightly larger than the 809 bp CaBP-22 cDNA insert, indicating that the deduced amino acid sequence of CaBP-22 is near full-length. CaBP-22 mRNA was detected in RNA fractions isolated from leaves of both soil grown and hydroponically grown Arabidopsis, but below the limits of detection in RNA isolated from roots, and developing siliques. Thus, CaBP-22 represents a new member of the EF-hand family of Ca(2+)-binding proteins with no known animal homologue and may participate in transducing Ca2+ signals to a specific subset of response elements. PMID- 8507825 TI - Calmodulin isoforms in Arabidopsis encoded by multiple divergent mRNAs. AB - Three new, unique cDNA sequences encoding isoforms of calmodulin (CaM) were isolated from an Arabidopsis cDNA library cloned in lambda gt10. These sequences (ACaM-4, -5, and -6) represent members of the Arabidopsis CaM gene family distinct from the three DNA sequences previously reported. ACaM-4 and -6 encode full-length copies of CaM mRNAs of ca. 0.75 kb. The ACaM-5 sequence encodes a partial length copy of CaM mRNA that is lacking sequences encoding the amino terminal 10 amino acids of mature CaM and the initiator methionine. The derived amino acid sequence of ACaM-5 is identical to the sequences encoded by two of the previously characterized ACaM cDNAs, and is identical to TCH-1 mRNA, whose accumulation was increased by touch stimulation. The polypeptides encoded by ACaM 4 and -6 differ from that encoded by ACaM-5 by six and two amino acid substitutions, respectively. Most of the deduced amino acid sequence substitutions in the Arabidopsis CaM isoforms occurred in the fourth Ca(2+) binding domain. Polymerase chain reaction amplification assays of ACaM-4, -5 and 6 mRNA sequences indicated that each accumulated in Arabidopsis leaf RNA fractions, but only ACaM-4 and -5 mRNAs were detected in silique total RNA. The six different CaM cDNA sequences each hybridize with unique EcoRI restriction fragments in genomic Southern blots of Arabidopsis DNA, indicating that these sequences were derived from distinct structural genes. Our results suggest that CaM isoforms in Arabidopsis may have evolved to optimize the interaction of this Ca(2+)-receptor protein with specific subsets of response elements. PMID- 8507826 TI - Isolation and characterization of wheat triticin cDNA revealing a unique lysine rich repetitive domain. AB - Polyclonal antibodies were raised against a purified 22 kDa triticin polypeptide (delta) and were used to screen a wheat seed cDNA library in the Escherichia coli expression vector lambda gt11. The isolated cDNA clones were grouped into three families based on their cross-hybridization reactions in DNA dot-blot studies. Southern blots of genomic DNAs extracted from ditelocentric and nullisomic tetrasomic lines of Chinese Spring wheat, probes with the excised cDNA inserts, indicated that one of the three families (9 clones) had triticin clones. This was finally confirmed by comparing the predicted amino acid sequences of two of these clones (lambda Tri-12, lambda Tri-25) with the published tryptic peptide sequences of triticin. The Southern blots also showed that there is at least one triticin gene located on the short arm of each of the homoeologous group 1 chromosomes (1A, 1B, 1D), although till now no triticin protein product has been identified for the chromosome 1B. The nucleotide sequence of the largest triticin cDNA clone lambda Tri-25 (1567 bp) is presented here, and its predicted amino acid sequence shows strong homology with the legumin-like proteins of oats (12S globulin), rice (glutelin) and legume seeds. A unique feature of the triticin sequence is that it contains a lysine-rich repetitive domain, inserted in the hypervariable region of the typical legumin-like genes. Northern blotting of total RNA extracted from different stages of the developing wheat seed revealed that the triticin gene expression is switched on 5-10 days after anthesis (DAA). There was a steady increase in the level of triticin mRNA until 20 DAA, after which it started decreasing. The maximum mRNA accumulation occurred between 17 and 20 DAA. These observations conform closely with the published data on triticin protein accumulation during grain development. PMID- 8507827 TI - Stress responses in alfalfa (Medicago sativa L.). 15. Characterization and expression patterns of members of a subset of the chalcone synthase multigene family. AB - We have identified five different full length chalcone synthase (CHS) cDNA clones from a cDNA library produced from transcripts isolated from an elicitor-treated alfalfa cell suspension culture. Nucleotide sequence similarity between the clones varied from 88-93%. Oligonucleotides based on divergent sequences in the 5'-untranslated regions of the clones could distinguish individual genes, or groups of genes, and their corresponding transcripts. Developmentally regulated expression of the CHS transcripts was predominantly in roots and root nodules; other unidentified members of the CHS gene family are expressed in stems, leaves and nodules. One of the CHS transcripts was strongly expressed in floral tissue. All the CHS transcripts studied were induced in elicitor-treated cell suspension cultures. Transcripts were also induced in roots in response to wounding or spraying with various elicitors, and in leaves infected with Phoma medicaginis (but not in wounded leaves). The induction kinetics of CHS2 transcripts were more rapid and/or transient than those of other members of the CHS family in CuCl2 treated roots and Phoma-infected leaves. The results are discussed in terms of the evolution and functions of the CHS gene family in legumes. PMID- 8507828 TI - Developmental regulation of an acyl carrier protein gene promoter in vegetative and reproductive tissues. AB - The expression of an Arabidopsis acyl carrier protein (ACP) gene promoter has been examined in transgenic tobacco plants by linking it to the reporter gene beta-glucuronidase (GUS). Fluorometric analysis showed that the ACP gene promoter was most active in developing seeds. Expression was also high in roots, but significantly lower in young leaves and downregulated upon their maturation. Etiolated and light-grown seedlings showed the same level of GUS activity, indicating that this promoter is not tightly regulated by light. Histochemical studies revealed that expression was usually highest in apical/meristematic zones of vegetative tissues. Young flowers (ca. 1 cm in length) showed GUS staining in nearly all cell types, however, cell-specific patterns emerged in more mature flowers. The ACP gene promoter was active in the stigma and transmitting tissue of the style, as well as in the tapetum of the anther, developing pollen, and ovules. The results provide evidence that this ACP gene is regulated in a complex manner and is responsive to the array of signals which accompany cell differentiation, and a demand for fatty acids and lipids, during organogenesis. PMID- 8507829 TI - Identification of a RAPD marker associated with somatic embryogenesis in alfalfa. AB - The current study was conducted to identify random amplified polymorphic DNA (RAPD) markers linked to genes controlling somatic embryogenesis in alfalfa. Segregation analyses of the somatic embryogenesis trait and the RAPD markers in an F1 population of 83 plants, derived from a cross between embryogenic A70-34 and non-embryogenic Arrow36 alfalfa plants, identified a polymorphic band that is associated with somatic embryogenesis. Based on the assumptions that somatic embryogenesis in alfalfa is controlled by two dominant genes with complementary effects and that the genotypes of A70-34 and Arrow36 are AAaaBbbb and aaaabbbb, respectively, the segregation data for the marker and the somatic embryogenesis trait in the F1s indicate that the marker is linked to the A locus. The maximum recombination fraction estimated for the linkage between the marker and the gene is 36.3%. PMID- 8507831 TI - Identification and expression of a cDNA from Daucus carota encoding a bifunctional aspartokinase-homoserine dehydrogenase. AB - Aspartokinase (EC 2.7.2.4) and homoserine dehydrogenase (EC 1.1.1.3) catalyze steps in the pathway for the synthesis of lysine, threonine, and methionine from aspartate. Homoserine dehydrogenase was purified from carrot (Daucus carota L.) cell cultures and portions of it were subjected to amino acid sequencing. Oligonucleotides deduced from the amino acid sequences were used as primers in a polymerase chain reaction to amplify a DNA fragment using DNA derived from carrot cell culture mRNA as template. The amplification product was radiolabelled and used as a probe to identify cDNA clones from libraries derived from carrot cell culture and root RNA. Two overlapping clones were isolated. Together the cDNA clones delineate a 3089 bp long sequence encompassing an open reading frame encoding 921 amino acids, including the mature protein and a long chloroplast transit peptide. The deduced amino acid sequence has high homology with the Escherichia coli proteins aspartokinase I-homoserine dehydrogenase I and aspartokinase II-homoserine dehydrogenase II. Like the E. coli genes the isolated carrot cDNA appears to encode a bifunctional aspartokinase-homoserine dehydrogenase enzyme. PMID- 8507830 TI - Identification of cis-acting elements involved in the regulation of the pathogenesis-related gene STH-2 in potato. AB - We have characterized a genomic clone containing the potato pathogenesis-related genes STH-2 and STH-21. The two genes are found 4 kb apart on the same chromosome and their sequences are highly similar. They present the same transcriptional orientation and are both interrupted by a single intron. A chimaeric gene consisting of 1015 bp of 5'-flanking sequence and part of the first exon of STH-2 fused to the bacterial beta-glucuronidase gene was highly-expressed in tubers of transgenic potato plants after wounding and elicitor treatments. The levels of activity observed in these transgenic plants parallel those observed for the accumulation of STH-2 mRNAs under similar conditions. This indicates that cis acting elements necessary for the proper activation of the gene are present within 1 kb of 5'-flanking sequences. Functional analysis of 5' deletions of the STH-2/GUS constructs by transient expression in leaf protoplasts revealed the presence of an upstream regulatory sequence between -135 and -52 which contains a TGAC motif, and a possible negative regulatory region between -52 and -28. A factor present in nuclear extracts of wounded potato tubers was found to bind specifically to nucleotides located between -135 to -105, suggesting that this region contains important cis-regulatory elements. PMID- 8507832 TI - Genetically improved potatoes: protection from damage by Colorado potato beetles. AB - Russet Burbank potato plants have been genetically improved to resist insect attack and damage by Colorado potato beetles (Leptinotarsa decemlineata (Say)) by the insertion of a cryIIIA gene encoding the insect control protein of Bacillus thuringiensis var. tenebrionis. A modified gene that dramatically improved plant expression of this protein was utilized. Its expression in Russet Burbank potato plants resulted in protection from damage by all insect stages in the laboratory and in dramatic levels of protection at multiple field locations. Analysis of these genetically modified potatoes indicated that they conform to the standards for Russet Burbank potatoes in terms of agronomic and quality characteristics including taste. PMID- 8507833 TI - Transcriptional characterization of an alpha-zein gene cluster in maize. AB - A cluster of five alpha-zein subfamily 4 (alpha-zein SF4) genes are present in a 56 kb region of the maize W22 genome. Two types of alpha-zein SF4 genes are in the cluster. One of the genes, termed a type 1 (T1) alpha-zein SF4 gene, contains no early in-frame stop codons. Four of the genes, termed type 2 (T2) alpha-zein SF4 genes, contain one or two early in-frame stop codons. The base sequence of the T1 alpha-zein SF4 gene is similar (> 90%) to the sequences of any of the four T2 alpha-zein SF4 genes. However, their sequences differ markedly at distances greater than -875 bp upstream from the translation initiation codon of the alpha zein coding region. This region of dissimilarity is well inside the functional 5' flanking region for the genes since a 1.8 kb transcript is initiated in this region and the sequences of the T2 alpha-zein SF4 genes are similar in this region. Two sizes of mRNA transcripts, 1.8 kb and 0.9 kb, were detected in a gene specific manner for 4 of the 5 genes in this alpha-zein SF4 gene cluster. One of the T2 alpha-zein SF4 genes had only the 0.9 kb transcript. The RNA level for the 0.9 kb transcript of the T1 alpha-zein SF4 gene was 5- to 10-fold higher than the transcript levels of any of the T2 alpha-zein SF4 genes. In each case, the amount of the 0.9 kb transcript detected was at least 5-fold higher than the amount of the 1.8 kb transcript. A cDNA clone with a sequence identical to a T2 alpha-zein SF4 gene was isolated, providing the first direct evidence for the transcription of T2 alpha-zein genes containing early in-frame stop codon(s) in maize endosperm. PMID- 8507834 TI - The primary structure of a cDNA for PsaN, encoding an extrinsic lumenal polypeptide of barley photosystem I. AB - A cDNA clone encoding a 15,501 Da photosystem I (PSI) subunit of barley was isolated using an oligonucleotide based on the NH2-terminal amino acid sequence of the isolated protein. The polypeptide, which migrates with an apparent molecular mass of 9.5 kDa on denaturing SDS-PAGE, has been designated PSI-N, and the corresponding gene is PsaN. Analysis of the deduced protein sequence indicates a mature protein of 85 amino acid residues and a molecular mass of 9818 Da. PSI-N is a hydrophilic, extrinsic protein with no predicted membrane-spanning regions. The transit peptide of 60 residues (5683 Da) contains a predicted hydrophobic alpha-helix, suggesting that the protein is routed into the thylakoid lumen. Thus, PSI-N is the second known lumenal protein component associated with PSI, together with PSI-F. PMID- 8507835 TI - Structure and expression of a barley acidic beta-glucanase gene. AB - A barley acidic beta-1,3-glucanase gene was recovered from a barley genomic library by homology with a partial cDNA of barley basic beta-1,3-glucanase isoenzyme GII. The gene, Abg2, is homologous to the PR2 family of pathogenesis related beta-1,3-glucanase genes. The ABG2 protein has 81% amino acid similarity to barley basic beta-1,3-glucanase GII. The ABG2 protein is encoded as a preprotein of 336 amino acids including a 28 amino acid signal peptide. A 299 bp intron occurs within codon 25. The mature ABG2 protein has a predicted mass of 32,642 Da and a calculated isoelectric point of 4.9. The second exon of the Abg2 gene shows a strong preference for G + C in the third position of degenerate codons. The Abg2 gene was functionally expressed in Escherichia coli. Abg2 mRNA is constitutively expressed in barley root; leaf expression of Abg2 mRNA is induced by mercuric chloride and infection by Erysiphe graminis f. sp. hordei. Southern blot analysis indicates that Abg2 is a member of a small gene family. PMID- 8507836 TI - Chemical regulation of transgene expression in plants. PMID- 8507837 TI - Early events in higher-plant embryogenesis. PMID- 8507838 TI - Isolation of cytochrome P-450 cDNA clones from the higher plant Catharanthus roseus by a PCR strategy. AB - Cytochrome P-450 monooxygenases are membrane-bound enzymes involved in a wide range of biosynthetic pathways in plants. An efficient PCR strategy for isolating cytochrome P-450 cDNA clones from plant cDNA libraries is described. A set of degenerate primers for PCR amplification was designed to recognize nucleotide sequences specifying the highly conserved haembinding region of cytochrome P-450 proteins. Using this primer set and a non-specific primer, complementary to either the poly(A) tail of the cDNA clones or a phage vector sequence, we isolated 16 different cytochrome P-450 cDNA sequences from a cDNA library of Catharanthus roseus. PMID- 8507839 TI - [Diagnosis and staging of blunt kidney trauma. A comparison of urinalysis, i.v. urography, sonography and computed tomography]. AB - In a retrospective study of 1230 patients with blunt abdominal or flank trauma, the results of microscopic urinalysis, urography, sonography, and computed tomography in the diagnosis and staging of renal injuries were compared. Haematuria was present in 98% of renal lacerations and in all pedicle injuries, whereas among 1038 patients without haematuria only one small laceration was found. The degree of haematuria showed no correlation with the severity of renal injury. 92 renal injuries were diagnosed radiologically, including 58 lacerations, 31 contusions, and three pedicle injuries. Computed tomography was performed in 39 lacerations and six contusions, and allowed correct diagnosis and staging in all cases. Urography established the correct diagnosis in 72%, and sonography in 85%. Sensitivity in the diagnosis of clinically relevant injuries (lacerations and pedicle injuries) was 98% (specificity: 99%), when both modalities were combined. Based on the results of our study, we suggest the use of sonography as a screening modality in blunt abdominal or flank trauma, and additional urography in case of haematuria. Computed tomography is the method of choice for exact staging of suspected renal injury. PMID- 8507840 TI - [A short infusion or a bolus injection of contrast medium in i.v. urography. Comparative density measurements in the kidney pelvic-caliceal system using sequential computed tomography]. AB - The rate of contrast injection during i.v. urography may vary considerably (bolus injection or drip infusion). The effect of 5 rates of injection (6, 12, 18, 36 and 72 ml/min) on the contrast density in the renal collecting system was examined over a period of 30 minutes. Measurements showed an inter-individual difference of more than 200% in each group. The intra-individual variations for different rates of injection were very slight; individual concentration in the kidney for a given dose depends only slightly on the rate of injection. There is no statistically significant improvement in contrast values as a result of a bolus injection. The reduced incidence of side effects justifies the use of bolus injections but pressure injections are unnecessary from a diagnostic point view. PMID- 8507841 TI - [Magnetic resonance tomographic identification and characterization of renal space-occupying lesions using GE-sequences with application of Gd-DTPA]. AB - In modern magnetic resonance imaging (MRI) gradient echo (GE) sequences have been shown to be superior to conventional spin echo (SE) sequences in characterising renal masses and staging renal tumours. In this study MRI was carried out in patients with renal masses (n = 97, histologically proven n = 43) using a fast GE sequence (multislice technique, TR/TE 80/5 ms) and an i.v. bolus application of gadolinium (Gd)-DTPA mostly in axial, in selected cases additionally in coronal slice orientation. MRI findings were compared with those of contrast-enhanced CT (n = 56). The results demonstrated that MRI under Gd-DTPA has a reliably good image quality and can characterise renal masses safely. Compared with CT in multislice MRI problems of partial volume effects can be reduced; complex renal cysts can be differentiated more safely from solid tumours with unclear CT findings due to a significantly higher contrast enhancement in MRI. PMID- 8507842 TI - [Treatment of stenosed or occluded hemodialysis shunts. Results of percutaneous angioplasty and combined radiologic-surgical therapy]. AB - The results of all recanalisations of stenosed and occluded haemodialysis shunts over a period of three years are reported; there were 112 percutaneous angioplasties and 40 combined radiological-surgical procedures. In 13% of cases a metallic endoprosthesis (wall stent) and in 3% Simpson's atherectomy catheter was used. The functional results were retrospectively evaluated for all 152 interventions which involved 60 orthoptic Brescia-Cimino shunts and 19 PTFE prostheses. In addition, the primary and total functions of the treated shunts were calculated. Cumulative function rate (percentage at a given time of effective shunts) for Brescia-Cimino shunts at one year was 80% and after two years 68.5%; for the PTFE prosthesis the corresponding figures were 83.8 and 75.5% respectively. The average number of interventions per patient was 2.3 with a range of 1-7. Total functional rate of all shunts following the first percutaneous procedure after one year was 78.2%, for combined radiological surgical procedures for the treatment of acute thromboses it was 68%. Comparison with the results of surgical treatment reported in the literature confirms the effectiveness of percutaneous or combined treatment of stenosed or acutely occluded haemodialysis shunts. The outstanding advantage of radiological intervention is its repeatability. PMID- 8507843 TI - [Long-term results of percutaneous atherectomy in peripheral arterial occlusive disease]. AB - In a retrospective study the indications and the long-term results of percutaneous atherectomy of a nonselected group of patients were analysed. From March 1988 to November 1989, 94 patients suffering from peripheral vascular disease were treated using Simpson's atherectomy technique. There were 132 lesions, 101 stenoses and 31 occlusions in a total of 94 patients. The primary success rate was 95%. After 12 months of follow-up the cumulative patency rate was 69% and after 24 months, 42%. After a follow-up period of 15 months patent arteries and recurrences were recorded and the results used to analyse the factors that influence patency after Simpson atherectomy. The patency rate is 71% in diabetics and 62% in non-diabetics. It is 51% in occlusions and 73% in stenoses. The patency rate in patients with fair runoff is 69%, in patients with poor runoff 60%. Comparing these results with historical studies concerning balloon dilation the results are poor. Residual stenoses after balloon dilation seem to be the optimal indication for percutaneous atherectomy. PMID- 8507844 TI - [Thrombotic and thromboembolic occlusions of leg arteries and bypasses. Short term versus long-term lysis]. AB - Since thrombolytic therapy is less invasive than operative thrombectomy, it is often used as initial treatment for thrombotic or thrombo-embolic occlusions of lower limb arteries or by-passes. We compared four patient groups with acute and subacute occlusions: 1. 19 patients with occluded by-passes treated by rapid lysis using 15.5 (2.5-35) mg rt-PA. 2. 12 patients with by-pass occlusions treated with initial rt-PA in a dose of 6.5 (2.5-12.5) mg followed by prolonged lysis with 5.6 (2.5-10) x 10(6) units of urokinase. 3. 16 patients with arterial occlusions treated by rapid lysis with 15 (2.5-25) mg rt-PA. 4. 14 patients with arterial occlusions given 10.5 (2.5-60) mg rt-PA followed by overnight treatment with 5.9 (2.5-15) x 10(6) units of urokinase. For by-pass recanalisation, prolonged lysis overnight had a success rate of 83% (10/12) which was better than short term lysis with a success rate of 74% (14/19). Similar results were obtained in arterial occlusions with a success rate of 86% (12/14) compared with 69% (11/16). Long term lysis did, however, have significantly more complications. In about one-third of cases further procedures had to be used in addition to lytic therapy. PMID- 8507845 TI - [The diagnosis of inflammatory muscular and vascular diseases using MRT with STIR sequences]. AB - The role of MRT in the prebiopsy diagnosis of muscular and vascular inflammatory conditions was evaluated prospectively and an optimal method of examination was investigated. 92 patients with a suspected diagnosis of myositis (60 cases) or vasculitis (32 cases) were examined, in each case two extremities were studied using transverse T1 and T2 weighted SE sequences and double echo STIR sequences on a 0.5 Tesla (56 patients) or 1.5 Tesla magnet (36 patients; T5/S15 Gyroscan, Philips). The site of the biopsy depended on the MRT findings. In 41 patients the suspected diagnosis was confirmed histologically, in two patients an infective myositis was diagnosed on clinical grounds despite negative histology. MRT demonstrated muscle oedema in 86% of patients. There were negative findings after immuno-suppressive therapy (two patients), in focal myositis (3 out of 4 patients) and in one of 7 patients with untreated vasculitis. Amongst 49 patients in whom the suspected diagnosis could not be confirmed there was muscle oedema in 11 cases (9 neuropathies out of 22, two myopathies out of 10). Oedema indicated inflammatory muscular or vascular disease with a sensitivity of 97% (except in treated patients and for focal myositis). The number of false negative biopsies can be greatly reduced by the use of MRT. PMID- 8507846 TI - [The use of the RACE technique for quantitative flow measurements. Evaluation using a clinically relevant flow model]. AB - A phantom has been designed for measuring flow velocities; using pipes of specified diameter and selectable pulse rates, flow rates varying from 0-250 cm/s can be determined. The measurements are made in a superconductive magnet with a field strength of 1.5 Tesla, employing a RACE technique. The reference technique was electromagnetic flow measurement. There was good linear correlation between the electromagnetic and the MRT results with a correlation coefficient of 0.98. It is necessary in the first place to estimate flow speed; if flow velocity is unknown initially, there is no correlation. Hence, in everyday use erroneous results may be obtained, particularly since one cannot always demonstrate vessels in all parts of the body without superimposition. Further clinical studies are required in various vascular territories to evaluate the usefulness of the RACE technique for flow measurements. PMID- 8507848 TI - [Intracranial lymphoma. Radiologic findings in 40 patients]. AB - We analysed the radiologically findings of 40 patients with histologically confirmed cerebral lymphoma but without AIDS in a retrospective study; 31 of these had primary cerebral lymphoma without any other manifestation of the disease. All patients had CT, 24 had angiography and in five patients MRT had been performed in addition. CT showed a solitary lesion in 60%, of these 62% had scalloped margins and 38% were nodular, 34% were isodense and 57% were hyperdense. Following contrast injection, there was increased density in 97% of the lesions. The most frequent localisation was in the region of the basal ganglia and the corpus callosum (33%), in the frontal lobes (30%) and in the temporal lobes (20%). Angiographically, 63% showed evidence of a space-occupying lesion, there were vascular irregularities in 33% and tumour contrast in 21%; in 25% of the patients angiography was normal. Early venous filling was not found in any case. T1 weighted sequences during MRT of 5 patients showed the tumour to be isointense or slightly hypointense. T2 weighted images showed the tumour to be hyperintense or with mixed signal intensities. PMID- 8507847 TI - [Differentiating between tumor and implant material in the postoperative sella using MRT]. AB - MRT criteria have been developed to distinguish between tumour and implant material following examination of 50 patients who had transsphenoidal hypophysectomies for tumours. Judgements were based on the postoperative hormonal status and the operation notes. Following contrast injection of Gd-DTPA and using T1 weighted spin-echo sequences, implant material appeared as sandwich-like, linear or circular structures. Residual recurrent tumour produced homogenous or non-homogenous aspects without marginal enhancement in 84% of cases. Postoperative displacement of the infundibulum to the opposite side was observed in 73% of patients with tumour remnants. Sensitivity of MRT was 70%, specificity 95%. There was a positive predictive value of 94% and a negative predictive value of 72% with an accuracy of 81%. This provides assistance in differentiating between tumour remnants and implant material. MRT is recommended as a method of examination for hypophyseal tumours to evaluate the success of surgery and where there is clinical doubt concerning residual or recurrent tumour. PMID- 8507849 TI - ["Inflammatory" disk degeneration. Magnetic resonance tomographic clinical picture]. AB - Disc degeneration, if it appears relatively early, progresses rapidly with inadequate bone compensation for stabilisation of the area, or in the presence of anatomic variation of the vertebrae with short sagittal diameters, there may be tissue proliferation and edema in the bone marrow and vascular granulations within the disc. We demonstrated these changes in 17 patients by means of MRT which shows edema of the bone marrow and contrast enhancement within the disc. All these patients had severe symptoms. There were no significant neurological findings since in general there was no disc prolapse. The MRT characteristics of this condition are described and correlated with the clinical and radiological features. The use of Gd-DTPA and subtractive spin-echo and gradient-echo sequences in the differential diagnosis from infective discitis is discussed. PMID- 8507850 TI - [A comparison of plain film, axial CT, 2D and 3D reconstructions in unstable spinal injuries following surgery]. AB - During a period of 18 months about 70 patients suffering from an unstable spinal injury were operated in the surgical department of our clinic. In 50 of these patients it was possible to correlate the results of preoperative radiography and CT with the operative findings. Several cases of distraction instability in the dorsal column had not been recognised in the preoperative radiologic evaluation. Therefore the rationale of this study was the question as to whether modern CT technology can help to avoid such wrong diagnoses. For that purpose radiographs, axial CT-scans of 2 mm thickness or less, sagittal and coronal 2D and (in 35 cases) 3D reconstructions were re-evaluated step by step by a specifically trained radiologist without knowing the operative findings. 15 additional lesions out of 28 were demonstrated and specifically classified as distraction instabilities of the dorsal column using the improved CT technology. PMID- 8507851 TI - [X-ray morphology of eosinophilic granuloma other than skull and spine]. AB - The radiological findings in 39 patients with a manifestation of eosinophilic granuloma (e.g.) other than skull and spine were evaluated. The localisation was found in the femur (26%), clavicula (20%) and ribs (20%). The lesions were located in 81% in the diaphysis and in 9.5% either in the epi-metaphysis or epi metadiaphysis. Associated periosteal reactions were observed in 38% of the patients, and were solid in 25%, lamellar in 10%, and in 3% complex. The majority of the tumours were classified as Lodwick IB lesions (41%). Lodwick IC lesions were seen in 13%, Lodwick II lesions in 25.5% and Lodwick III lesions in 20.5% of the patients. In patients below the age of 20 years the eosinophilic granuloma is characterised by a Lodwick IB lesion without or with a solid periosteal reaction, which allows differentiation from Ewing's sarcoma or osteomyelitis. Contrariwise, in patients above 20 years of age the e.g. appears with a higher Lodwick grade. Hence, differentiation, X-ray morphology, between e.g., metastasis, lymphoma, and multiple myeloma does not seem possible. PMID- 8507852 TI - [The radiologic clinical picture of primary bone lymphoma]. AB - Primary lymphoma of bone is a rare form of non-Hodgkin lymphoma which involves a single bone and has a relatively good prognosis following radiation therapy. We observed 17 histologically verified cases and found 97 cases in the literature. This rare tumour may occur at any time in adults and usually affects the metaphyses of long bones. It produces osteolytic changes and usually only mild periosteal reactions. Radiologically as well as histologically, differentiation from other highly malignant bone tumours is extremely difficult and sometimes impossible. A correct diagnosis can only be made from an accurate knowledge of the radiological appearances, localisation of the tumour and age of the patient. PMID- 8507853 TI - [Transpopliteal laser-assisted balloon angioplasty of the blood vessels of the lower limbs with subsequent femoropopliteal bypass]. PMID- 8507854 TI - [Central pulmonary embolism as a chance finding of computed tomography. An analysis of 3 cases]. PMID- 8507855 TI - Dissection of pulmonary artery as a complication of pulmonary angiography. PMID- 8507856 TI - [Radiologic and differential diagnostic aspects of primary lymphoma of the lung (BALT lymphoma]. PMID- 8507857 TI - [Juxta-articular pneumatocele of the ilium bone]. PMID- 8507858 TI - Ex vivo expansion of hematopoietic stem and progenitor cells--robbing Peter to pay Paul? PMID- 8507859 TI - Erythroid and nonerythroid spectrins. AB - Recent developments have contributed important information to understanding the role of spectrins in the RBC membrane skeleton and nonerythroid cells. Many questions can now be framed, informed by structural knowledge of various spectrin subunit types and alternatively spliced variants, that previously could not have been addressed. Their solution in the coming years will likely lead to further advances with direct relevance to biology and medicine. PMID- 8507860 TI - The fibrinogen sequences that interact with thrombin. PMID- 8507861 TI - CD4dull+ hematopoietic progenitor cells in murine bone marrow. AB - CD4+ cells comprise approximately 3% to 6% of murine bone marrow (BM) cells. The majority are CD4dull+, but there are two distinct sub populations: CD4 brightly positive Gr-1- cells (CD4hiGr-1-) and CD4+ Gr-1+ cells (CD4loGr-1lo). CD4hiGr-1- cells are considered to be mature T cells by cell surface antigen expression and morphology. CD4loGr-1lo cells, which comprise approximately 0.6% of the BM cells, express small amount of B220 and Thy1 antigens. Interestingly, colony-forming units (CFU)-spleen and CFU-C are not enriched in this population. However, when injected into lethally irradiated mice, CD4loGr-1lo cells were shown to differentiate into T-cell, B-cell, and myelo-monocyte lineages when assayed 26 weeks after transplantation. Furthermore, donor-derived CD4loGr-1lo cells were present in the recipients' BM at least 16 weeks after transplantation. These observations suggest that murine CD4loGr-1lo cells in BM have self-renewal capability and retain the ability to differentiate into at least three lineages in long-term hematopoiesis. PMID- 8507862 TI - Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. AB - The expression of the hematopoietic transcription factors GATA-1, GATA-2, and GATA-3 was studied in eosinophils and basophils. Eosinophils express mRNA for GATA-1, GATA-2, and GATA-3. Basophils express GATA-2 and GATA-3. Treatment of HL 60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes, whereas levels of GATA-2 mRNA remained relatively constant. The presence of mRNA for these proteins in eosinophils and basophils suggests that gene transcription in these lineages may be regulated by GATA-binding proteins. PMID- 8507863 TI - The functional expression of tissue factor by fibroblasts and endothelial cells under flow conditions. AB - The expression of tissue factor (TF) by a variety of vascular cell types under physiologic flow conditions is critical to factor X activation and in vivo clotting. Therefore, in a parallel-plate flow chamber (volume 40 microL) we mounted monolayers of human embryonic fibroblasts (FBs) or interleukin-1 alpha (IL-1 alpha) (5 U/mL x 4 hours)-stimulated human umbilical vein endothelial cells (ECs). Inflow buffer contained 10 nmol/L factor VIIa, 100 nmol/L factor X, and 2.0 mmol/L CaCl. With FBs, production of factor Xa (product of outflow concentration of factor Xa-and flow rate) increased 200-fold over the range of shear stress from 0 to 2.7 dynes/cm2. Production values (mean +/- SE (N)) were 7.93 +/- 0.024 (6), 312 +/- 7.3 (6), 688 +/- 33.1 (8), 1,033 +/- 119 (6), and 1,601 +/- 183 (7) fmol/cm2.minute at shear stresses of 0, 0.27, 0.68, 1.35, and 2.7 dynes/cm2, respectively. Further experiments at 0.68 dynes/cm2 indicated that factor Xa production increased with factor X concentration over the range from 3 to 100 nmol/L, but changed little from 300 to 1,000 nmol/L. With ECs, production was 0.13 +/- 0.86 (6), 8.17 +/- 1.65 (13), and 1.66 +/- 1.66 (5) fmol/cm2.minute at 0, 0.68, and 2.7 dynes/cm2, respectively. However, in the presence of an antibody directed against tissue factor pathway inhibitor (TFPI) production with ECs was augmented to 16.46 +/- 0.80 (8), 149.8 +/- 18.6 (8), and 48.9 +/- 10.3 (10), respectively, at these same shear stresses. Control experiments with factor VIIa, factor X, or both absent confirm for both cell types the specificity of the reaction for the TF pathway. Similarly, specificity for TF itself is shown by the virtual absence of factor Xa generation in the presence of the monoclonal antibody HTF1-7B8 directed against human TF. We conclude that ECs, even when activated, are normally unable to generate significant quantities of factor Xa in the presence of factors X and VIIa. However, significant quantities of factor Xa are possible in the presence of an inhibitor of TFPI. On the other hand, production of factor Xa by fibroblasts is markedly augmented by shear stress, yet independent of the availability of substrate factor X above an inflow concentration of 100 nmol/L. The latter suggests a direct effect of flow on the fibroblast monolayers, not substrate limitation by convective diffusion. PMID- 8507864 TI - In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. AB - Using a novel in vitro selection/amplification technique, we have recently identified a new class of thrombin inhibitors based on single-stranded DNA oligonucleotides. One oligonucleotide, GGTTGGTGTGGTTGG (thrombin, aptamer), showed potent anticoagulant activity in vitro. We have initiated pharmacologic studies in cynomolgus monkeys to study the thrombin aptamer's in vivo anticoagulant properties. Upon infusion of the thrombin aptamer, anticoagulation was rapidly achieved, with a plateau reached within 10 minutes. There was a linear dose-response relationship between thrombin aptamer infusion rate and prolongation of plasma prothrombin time. Ten minutes after the infusion was stopped, no prolongation of prothrombin time was observed, indicating that the thrombin aptamer has an extremely short in vivo half-life, estimated to be 108 +/ 14 seconds. In addition, inhibition of thrombin-induced platelet aggregation in platelet-rich plasma was observed ex vivo without an effect on collagen-induced aggregation, indicating that the inhibition was specific for thrombin and not due to a nonspecific inhibitory effect on platelets. To exploit the short in vivo half-life of the thrombin aptamer, its ability to achieve regional anticoagulation in an extracorporeal hemofiltration circuit in sheep was tested. Doubling of the prothrombin time in the circuit was observed, whereas the systemic prothrombin time was minimally prolonged. We conclude that the thrombin aptamer is a potent anticoagulant in vivo, and specifically inhibits thrombin induced platelet aggregation ex vivo. The rapid onset of action and short half life in vivo suggest that the thrombin aptamer may be useful in anticoagulation with extracorporeal circuits and may have distinct advantages in certain acute clinical settings. PMID- 8507865 TI - Anticoagulant function of a 24-Kd fragment isolated from human fibrinogen A alpha chains. AB - A fibrinogen fragment obtained by limited-plasmin proteolysis has been isolated and purified to apparent homogeneity by gel filtrations. This fragment, denoted as 24-Kd fragment, has an apparent M(r) approximately 24,000 and contains an N terminal sequence of met-glu-leu-glu-arg-pro-gly-gly-asn-glu-ile. The fragment contains a large number of acidic amino acid residues, and its amino acid composition is similar to several fibrinogen A alpha chains degradation fragments isolated previously. It corresponds to a peptide of the fibrinogen A alpha chains, the N-terminal of which starts at alpha Met-240. This peptide delays thrombin plasma clotting time. It does not bind calcium ions and does not inhibit thrombin's amidolytic activity. It binds to immobilized fibrin but not fibrinogen. It also inhibits the polymerization of desAA and desAABB fibrin monomers by simultaneously decreasing the maximum rate and the maximum level of the polymerization reaction. However, the initial lag period of this reaction is not affected by the fragment. PMID- 8507866 TI - Interleukin-4 stimulates expression of urokinase-type-plasminogen activator in cultured human foreskin microvascular endothelial cells. AB - The effect of interleukin-4 (IL-4) on the fibrinolytic system of human microvascular and macrovascular endothelial cells in culture was studied. Only foreskin microvascular endothelial cells (EC) responded to IL-4 treatment with a dose- and time-dependent increase in urokinase-type plasminogen activator (u-PA) (control: 3.0 +/- 0.8 ng/10(5) cells/24 h; 200 U/mL IL-4: 6.7 +/- 0.8 ng/10(5) cells/24 h), whereas human macrovascular EC remained unaffected. A maximum effect was achieved with 200 U/mL IL-4. Little u-PA activity was detected in the conditioned media of human foreskin microvascular EC (HFMEC) treated without and with IL-4 before plasmin treatment (control: 0.03 +/- 0.003 IU/10(5) cells/20 h; 200 U/mL IL-4: 0.09 +/- 0.007 IU/10(5) cells/20 h). These values increased to 0.18 +/- 0.02 IU/10(5) cells/20 h and 0.53 +/- 0.04 IU/10(5) cells/20 h, respectively, after plasmin treatment, indicating that u-PA is released by HFMEC predominantly in its inactive precursor form single-chain u-PA (scu-PA). u-PA activity increased also in the cell lysates of HFMEC up to 2.5-fold after IL-4 treatment. Plasminogen activator inhibitor type-1 (PAI-1) levels produced by HFMEC remained unaffected by IL-4, whereas tissue-type plasminogen activator (t PA) levels were slightly decreased when HFMEC were treated with IL-4. These findings were also reflected in the specific mRNA levels as determined by Northern blotting. u-PA-specific mRNA increased significantly in HFMEC in the presence of IL-4, whereas t-PA mRNA and PAI-1-specific mRNA in HFMEC and u-PA specific mRNA in human saphenous vein EC (HSVEC) remained unaffected by IL-4 treatment. Our findings suggest a role for IL-4 in the process of angiogenesis, in addition to its known proliferative effect on human microvascular EC, by increasing the fibrinolytic potential of such EC, thereby facilitating extracellular proteolysis and cell migration. PMID- 8507867 TI - A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training. AB - A computer simulation of the circulatory system was used to kinetically model secretion, inhibition, and clearance of tissue plasminogen activator (t-PA) during three different processes that increase active t-PA levels: epinephrine infusion, exercise, and endurance training. Infusion of epinephrine stimulated an increase in t-PA secretion that was proportional to the plasma epinephrine concentration. In addition, epinephrine infusion increased hepatic blood flow and t-PA clearance, thus slowing the increase of plasma t-PA levels. During exercise, t-PA levels increased due both to increased t-PA secretion and to decreased clearance secondary to reduced hepatic blood flow. The increase in t-PA secretion during exercise was directly proportional to the epinephrine concentration in blood with the same ratio of t-PA secretion to epinephrine as found during epinephrine infusion, suggesting that increased plasma epinephrine during exercise was the primary stimulus for t-PA secretion. Lastly, the simulation predicted that 6 months of endurance training produced a decrease in resting plasminogen activator inhibitor type 1 (PAI-1) secretion, resulting in less t-PA inhibition and an overall increase in active t-PA after training. Accurate analysis of the regulation of active t-PA levels in blood required simultaneous modeling of t-PA and PAI-1 secretion, hepatic clearance, and inhibition of t-PA by PAI-1. PMID- 8507868 TI - Neonatal alloimmune thrombocytopenia due to a new platelet-specific alloantibody. AB - An infant with severe neonatal alloimmune thrombocytopenia is described in whom an antibody directed at a new platelet-specific alloantigen, Ca (HPA-6b), is implicated. The new alloantigen is of low frequency in the population and was localized to platelet glycoprotein (GP) IIIa. Immunoprecipitation studies using murine monoclonal antibodies specific for the GP complex IIb-IIIa and GPIIIa alone (AP2 and AP3) suggest that the location of the Ca epitope on GPIIIa may be near the binding site for AP3. Neonatal alloimmune thrombocytopenia associated with Ca is likely to be as severe as that seen in cases due to incompatibilities for the HPA-1 (PIA) and HPA-4 (Pen) platelet alloantigen systems, because each is located on GPIIIa, a densely represented molecule on the platelet surface. PMID- 8507869 TI - Thrombin-induced release of active basic fibroblast growth factor-heparan sulfate complexes from subendothelial extracellular matrix. AB - The angiogenic factor, basic fibroblast growth factor (bFGF), is sequestered and protected by binding to heparan sulfate proteoglycans (HSPG) in the subendothelial extracellular matrix (ECM). Release of ECM-bound bFGF provides a novel mechanism for regulation of cell proliferation and neovascularization in normal and pathologic situations. Exposure of ECM to thrombin, the final activation product of the clotting cascade, resulted in release of high molecular weight HSPG-bFGF complex, as indicated by its immunoprecipitation with anti-bFGF antibodies, susceptibility to degradation by bacterial heparinase, and inhibition of its mitogenic activity in the presence of neutralizing anti-bFGF antibodies. The ECM-resident bFGF-HSPG complex was not released by thrombin in the presence of hirudin or antithrombin III, or by catalytically blocked thrombin preparations. A threefold to fivefold higher mitogenic activity was released by thrombin from ECM that was preheated (1 hour, 80 degrees C), as compared with native ECM. This difference is attributed to heat stable bFGF-HSPG complexes that are more readily released after heat treatment of the ECM and to activation and release of ECM-resident transforming growth factor-beta (TGF-beta) activity. Our results indicate that the large reservoir of proteolytic activity present in plasma in the form of prothrombin may participate in release from the subendothelial ECM of biologically active bFGF and TGF-beta, depending on the accessibility of thrombin. Thrombin may gain access to the subendothelium on clot formation after tissue injury and as a result of the conversion of prothrombin to thrombin induced by the ECM itself. PMID- 8507870 TI - Incidence of inhibitor development in a group of young hemophilia A patients treated exclusively with lyophilized cryoprecipitate. AB - The incidence of neutralizing isoantibody formation to infused factor VIII in a cohort of 67 hemophilia A patients, born between January 1, 1971 and April 30, 1990, who had been treated exclusively with lyophilized cryoprecipitate, was 6% (5.3 per 1,000 patient years of observation). The age-dependent cumulative risk was 4.6% at 4 years of age and 6.7% at 8 years of age. Recent reports in patients treated with a variety of more pure concentrates show a much higher incidence of inhibitor formation and tend to be used as a reference when new concentrates are introduced. We believe that a patient group, such as the one studied here, is a more suitable reference population because these patients have been exclusively treated with a single factor VIII preparation. PMID- 8507871 TI - Identification of a novel human immunodeficiency virus strain cytopathic to megakaryocytic cells. AB - Impaired megakaryocytopoiesis may be a contributing factor to thrombocytopenia associated with human immunodeficiency virus (HIV) infection. Because HIV isolates differ in their host range and pathogenicity, we investigated whether HIV strains with demonstrable cell tropism and increased cytopathicity for megakaryocytes could be derived from the blood of thrombocytopenic HIV-infected individuals. We derived a strain, HIV-WW, from the peripheral blood of an individual with severe thrombocytopenia and found the virus to be highly and specifically cytotoxic to CMK and DAMI megakaryocytic cells. CMK and DAMI cells were not permissive for the virus and HIV-WW induced cytopathicity for these megakaryocytic cells did not depend on viral replication. The CD4 N-terminus binding domain of the HIV gp120 envelope protein did not appear to be involved in determining the cytopathic phenomenon. HIV may impair megakaryocytopoiesis through interactions at the cell surface in some cases rather than through viral entry and intracellular replication. PMID- 8507872 TI - Production and characterization of a bispecific IgG capable of inducing T-cell mediated lysis of malignant B cells. AB - Bispecific monoclonal antibodies (bsabs) recognizing both CD3 and a tumor antigen can redirect T-cell-mediated cytotoxicity toward cells bearing that antigen. Such bsabs have been shown to be more effective than monospecific monoclonal antibodies (MoAbs) at preventing tumor growth in animal models of B-cell malignancy. The current studies describe the production and preliminary evaluation of a bsab designed to induce the lysis of malignant human B cells by human T cells. The bsab was obtained from a hybrid-hybridoma cell line produced by fusing OKT3-secreting hybridoma cells with hybridoma cells that secrete 1D10. 1D10 is an MoAb that recognizes an antigen found on a majority of malignant human B cells that has not been detected to a significant degree on normal resting or activated lymphocytes. High performance liquid chromatography (HPLC) was used to separate bsab from monospecific antibodies that were also present in the hybrid hybridoma antibody product. The bsab was then evaluated in vitro for its ability to induce lysis of malignant B cells by activated T cells. The bsab consistently induced extensive lysis in vitro of 1D10 (+) cells, including both cell lines and cells obtained from patients with a variety of B-cell malignancies. No such effect was seen with activated T cells alone or activated T cells with monospecific antibody. No increased lysis was seen with 1D10 (-) cell lines. The bsab also mediated lysis of malignant B cells by autologous T cells. We conclude bsab containing an OKT3 arm and a 1D10 arm can induce T-cell-mediated lysis in a manner that is both potent and specific. This supports further evaluation of this bsab as a potential immunotherapy of B-cell malignancy. PMID- 8507873 TI - Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells. AB - Interleukin-6 (IL-6) has been suggested to play a major role in multiple myeloma. To investigate the source and target cells of IL-6 activity in multiple myeloma, expression of the cytokine and its receptor genes by myeloma plasma cells was studied. Tumor cells were sorted from bone marrow aspirates of myeloma patients using 4-parameter gating. Myeloma cells were identified as CD38high CD45negative intermediate and by their light-scatter characteristics. Sorted cells contained only myeloma plasma cells. No contaminating cells were present as determined morphologically, by monoclonal cytoplasmic Ig analysis, and by polymerase chain reaction (PCR) amplification of marker genes. Myeloma cells from 45% of patients expressed IL-6. IL-6 receptor transcripts were found in 68% of the specimens. IL 6 gene expression correlated with expression of the IL-6 receptor gene (P < .005). Correlations observed between the expression of CD45, a protein tyrosine phosphatase expressed by B lymphocytes but not by plasma cells, and the expression of the IL-6 and IL-6-receptor genes (P < .0002 and P < .005, respectively) suggest that an autocrine IL-6 loop is functioning in myeloma in preplasma cells. PMID- 8507874 TI - Application of chromosome microdissection probes for elucidation of BCR-ABL fusion and variant Philadelphia chromosome translocations in chronic myelogenous leukemia. AB - Fluorescence in situ hybridization (FISH) has become an increasingly important method for assessing chromosome rearrangement. The reciprocal translocation constituting the Philadelphia (Ph) chromosome [t(9;22)(q34;q11)] characterizes more than 90% of patients with chronic myelogenous leukemia (CML). However, in the remaining cases the Ph chromosome (genetically characterized by the fusion of the BCR-ABL genes) is thought to arise through complex translocations that are often not readily apparent using routine chromosome-banding analysis. For this reason we have developed unique band-specific probes for two-color FISH that detect unequivocally the Ph chromosome, and its derivatives. Results of the application of these probes are illustrated by analysis of 11 cases of CML (9 of which contain "variant" translocations). The probes were generated by chromosome microdissection and in vitro amplification of the bands involved in the Ph translocation, leading to an extremely fast and sensitive approach to identify this alteration in leukemic cell populations. PMID- 8507875 TI - Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. AB - The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information. PMID- 8507876 TI - Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. AB - Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3-tetrahydrofolate and five patients with defects in the synthesis of CH3-Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level. PMID- 8507877 TI - Iron distribution in Belgrade rat reticulocytes after inhibition of heme synthesis with succinylacetone. AB - We have used succinylacetone (4,6-dioxoheptanoic acid), a specific inhibitor of delta-aminolevulinic acid dehydrase, to gain insight into the defect in iron metabolism in the Belgrade anemia. The Belgrade rat has an inherited microcytic, hypochromic anemia associated with poor iron uptake into developing erythroid cells. Succinylacetone inhibits heme synthesis, leading to nonheme iron accumulation in mitochondria and cytosol of normal reticulocytes. When succinylacetone is used to inhibit Belgrade heme synthesis, iron from diferric transferrin does not accumulate in the stromal fraction that contains mitochondria, nor does 59Fe accumulate in the nonheme cytosolic fraction. Hence, the defect in the Belgrade rat reticulocyte occurs in the endocytic vesicle or in a step subsequent to iron transit from the vesicle but before the nonheme cytosolic or mitochondrial iron fractions. Therefore, the mutation affects either the release of iron from transferrin or iron transport from the vesicle to the mitochondrion. PMID- 8507878 TI - Clinical and blood bank factors in the management of platelet refractoriness and alloimmunization. AB - Numerous independent and interdependent factors are involved in the posttransfusion platelet response. Factors such as ABO match and platelet age are related to circumstances potentially under the control of the blood bank physician and therefore may permit circumvention by an active transfusion service. On the other hand, factors such as fever or sepsis may be unavoidable, being related more to the individual patient or clinical condition. To evaluate which factors could be circumvented, we prospectively followed the 1-hour corrected count increments (CCIs) for 962 single-donor apheresis platelet transfusions to 71 refractory hematologic oncology inpatients, with concomitant recording of implicated factors. Stepwise regression analysis allowed for determination of which concurrent and confounding clinical-, patient-, and blood bank-related factors significantly affected the CCIs. Although many implicated factors proved to be independently associated with an increased or decreased CCI, we found that no single variable consistently explained the CCI variation across the patient population. Each patient appeared sensitive to one or a few particular factors, but because of marked intraindividual variation, it was not possible to identify a priori which factors were important for a given patient. The single exception was a solid-phase red blood cell adherence assay used to cross-match platelets, but only for alloimmunized patients. We also evaluated the utility of requesting HLA-matched platelets from the local suppliers and maintained a clear distinction between platelets simply ordered as HLA matched and actually HLA-identical platelets. Accounting for the confounding clinical-, patient-, and blood bank-related factors, the cross-match assay was a better predictor of an adequate CCI than ordering platelets as HLA matched. PMID- 8507879 TI - 52Fe for additional marrow ablation before bone marrow transplantation. AB - The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity. PMID- 8507880 TI - Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. AB - Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl-2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR-detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR-detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy. PMID- 8507881 TI - Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver. AB - Venocclusive disease (VOD) of the liver is the major dose-limiting complication of pretransplant regimens for bone marrow transplantation. Recent reports from different groups point to the involvement of the hemostatic mechanism in the development of VOD. We measured the naturally occurring anticoagulants protein C, antithrombin III, and protein S in 45 patients undergoing bone marrow transplantation for hematologic malignancies before cytoreductive therapy and after transplant. The aim of this prospective study was both to evaluate the status of the naturally occurring anticoagulant pathway in patients who develop VOD compared with patients who do not, and to find a predictive marker of VOD. In transplant patients, protein C decreased from before cytoreductive therapy to posttransplant, whereas protein S and antithrombin III did not. In a multivariate analysis, protein C was the only variable that could independently discriminate between VOD and non-VOD patients at all times. Discriminant function analysis established that low protein C levels before cytoreductive therapy predicted the occurrence of VOD with good sensitivity and specificity. PMID- 8507882 TI - Granulocyte-macrophage colony-stimulating factor-induced antibody-dependent cellular cytotoxicity in bone marrow macrophages: application in bone marrow transplantation. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to induce antitumor activity in peripheral blood monocytes. We examined the role of GM-CSF on bone marrow (BM) macrophages in inducing antibody-dependent cellular cytotoxicity (ADCC) against murine and human tumor cells in vitro and in vivo with the aim of applying this approach in an autologous bone marrow transplantation (BMT) setting. GM-CSF induced a potent ADCC in BM macrophages against a murine melanoma in vitro. Treatment with GM-CSF alone or with antibody alone had no effect, whereas therapy with combination of both these agents resulted in a significant reduction in dissemination of melanoma both in a nontransplant as well as in BMT settings, with results being more optimal in the latter setting. Adoptive transfer of BM macrophages harvested from mice undergoing therapy with GM-CSF plus antibody significantly reduced the dissemination of melanoma in secondary recipients but only after irradiation, not in intact mice. GM-CSF also induced significant ADCC in human BM macrophages against a melanoma and a lymphoma in vitro and against a lymphoma implanted in nude mice in vivo. Again, these effects were more optimal after chemotherapy. These data suggest that treatment with GM-CSF plus tumor-specific monoclonal antibodies after BMT may induce an antitumor effect and help eradicate the minimal residual disease. PMID- 8507883 TI - Expression of multidrug resistance gene (MDR1) in normal hematopoietic cells. PMID- 8507884 TI - Expression of T-cell receptor V beta regions in granular lymphocyte-proliferative disorders. PMID- 8507885 TI - Activation of factor XI. PMID- 8507886 TI - 2-Chlorodeoxyadenosine in the treatment of chronic refractory immune thrombocytopenic purpura. PMID- 8507887 TI - Expression of cell adhesion molecules in jejunum biopsies of children with coeliac disease. AB - The composition of inflammatory cells as well as the expression of cell adhesion molecules (LFA-1/CD11a, ICAM-1/CD54, CD36) in jejunal biopsies from children with active, untreated coeliac disease (CD) has been analyzed and compared with control biopsies. In CD the number of intraepithelial and lamina propria T cells was greater than in controls. ICAM-1 was found on most cells in the lamina propria; many of them expressed LFA-1 as well. In contrast, no ICAM-1+ and a few LFA-1+ cells were noticed in the epithelium. The brush border from control biopsies reacted with HLADR and anti-CD36. In CD, de novo expression of HLADR was found in the cytoplasm of villous and cryptal enterocytes in contrast, CD36 disappeared from the brush border and no expression of ICAM-1 on the inflamed epithelium was noticed. The results indicate that adhesion molecules other than LFA-1, ICAM-1 and CD36 may be involved in the cellular interactions occurring in the intraepithelial compartment in CD; the lack of ICAM-1 and the reduced expression of LFA-1 on intraepithelial lymphocytes might reflect a defective activation of these cells. Several macrophages were found in the lamina propria in cases of CD; some of them were located beneath the surface epithelium, showed a spindle/dendritic morphology, and expressed the HLADR+, CD36+, CD11a- phenotype. These cells might be stimulated by luminal antigens and might play an important role in subsequent activation of T cells in the lamina propria. PMID- 8507888 TI - A multicentre randomized clinical trial of recombinant alpha-2a interferon therapy in patients with chronic hepatitis B. AB - Fifty six previously untreated patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than 1 year with detectable serum levels of hepatitis B virus DNA (HBV-DNA) and a liver biopsy performed in the 6 months before enrollment, were randomized to receive recombinant alpha-2a interferon at doses of 3MU intramuscolarly thrice weekly for 6 months or no treatment. Treated and untreated patients had similar clinical characteristics in terms of ALT elevation, HBV-DNA levels, and degree of liver damage. Twenty one had chronic persistent or lobular hepatitis; 28 had chronic active hepatitis and 7 had cirrhosis. The percentages of patients who lost HBeAg at month 6, 12 and 18 were 22%, 32% and 38% in the treated group, and 16%, 20% and 37% in the controls (differences = ns). At the same time intervals, HBV-DNA detected by dot spot hybridization, cleared off in 39%, 39% and 41% of treated patients as compared to 16%, 36% and 37% of controls (difference = p < 0.05 for HBV-DNA clearance at month 6). At the end of follow-up, 12 treated patients (41%, including 8 antiHBe seroconverters) and 10 untreated controls (42%, including 6 anti-HBe seroconverters) had normal aminotransferase levels. Conclusions show that in patients with chronic hepatitis B, clearance of HBV-DNA but not of HBeAg was hastened by a 6-month treatment with low doses of recombinant alpha-2a interferon. PMID- 8507889 TI - Adenocarcinoma of the duodenal bulb in a young coeliac woman. AB - Coeliac sprue patients display an increased frequency of malignant neoplasms of the gastrointestinal tract. These neoplasms are chiefly represented by lymphomas, occurring in patients over 50. We describe the onset of a duodenal adenocarcinoma in a young woman with coeliac disease and discuss the unusual features of this case. PMID- 8507890 TI - S-adenosyl-L-methionine and the liver. PMID- 8507891 TI - Skeletal muscle free amino acids in liver cirrhosis. PMID- 8507892 TI - Regulation by insulin of branched chain amino acid metabolism in cirrhosis. PMID- 8507893 TI - Amino acid and protein metabolism in diabetes mellitus. PMID- 8507894 TI - Who should carry out diagnostic ultrasound? PMID- 8507895 TI - Domains of E1A that bind p105Rb, p130, and p300 are required to block nerve growth factor-induced neurite growth in PC12 cells. AB - Nerve growth factor (NGF) causes PC12 cells to cease division and undergo sympathetic neuron-like differentiation, including neurite outgrowth. We have tested whether differentiation and division share overlapping control mechanisms in these cells. To do this, we have perturbed the activity of proteins known to participate in cell-cycle regulation by introducing the E1A oncogene or its mutant forms via microinjection into PC12 cells. The E1A protein binds to several putative cell cycle control proteins, including p105Rb (the product of the retinoblastoma susceptibility gene), as well as others of unknown function such as p130, p107, and p300. Similar to previous results, we find that wild-type E1A abrogates NGF-induced neurite extension. However, NGF does cause neurite outgrowth in the presence of E1A mutants known to have greatly reduced binding to either p105Rb and p130 or p300. Our experiments suggest that p105Rb, p130, and p300 may participate either in E1A-mediated inhibition of differentiation or in the NGF signal transduction pathway. We also report here that NGF affects phosphorylation of p105Rb, suggesting that Rb mediates at least some of NGF's effects. Our results raise the possibility that putative cell-cycle control proteins may participate not only in NGF-induced cessation of division but also in differentiation. PMID- 8507896 TI - Species-specific inhibition of fertilization by a peptide derived from the sperm protein bindin. AB - The sperm protein bindin is responsible for the species-specific adhesion of the sperm to the egg. The regions of the bindin molecule responsible for forming the contact between the sperm and the egg were investigated by measuring the ability of peptides representing various regions of the bindin sequence to inhibit fertilization. Twenty-four peptides were studied: 7 based on the Strongylocentrotus purpuratus bindin sequence, 11 based on the S. franciscanus bindin sequence, and 6 control peptides. Values for the concentration of peptide required to inhibit 50% of the productive sperm contacts (IC50) were extracted from experimental measurements of the extent of fertilization in the presence of various concentrations. of these peptides. The IC50 value averaged 220 microM for the control peptides. Active peptides representing certain specific subregions of the bindin sequence displayed IC50 values < 10% of the average value for control peptides, and the IC50 for the most potent of the peptides tested was only approximately 1% of the control peptide value (IC50 = 2.2 microM). Furthermore, we found that a peptide representing a particular region of the S. franciscanus bindin sequence that differs from the S. purpuratus bindin sequence inhibits fertilization species specifically. For the reaction of S. purpuratus sperm and eggs, the IC50 of this peptide was approximately 120 microM, whereas for the reaction of S. franciscanus sperm and eggs it was only 8.6 microM. These results demonstrate that a few specific regions of the bindin molecule are involved in the sperm-egg contact and that certain of these regions mediate the species specificity of the interaction in a sequence-specific manner. PMID- 8507897 TI - Disruption of endoplasmic reticulum to Golgi transport leads to the accumulation of large aggregates containing beta-COP in pancreatic acinar cells. AB - When transport between the rough endoplasmic reticulum (ER) and Golgi complex is blocked by Brefeldin A (BFA) treatment or ATP depletion, the Golgi apparatus and associated transport vesicles undergo a dramatic reorganization. Because recent studies suggest that coat proteins such as beta-COP play an important role in the maintenance of the Golgi complex, we have used immunocytochemistry to determine the distribution of beta-COP in pancreatic acinar cells (PAC) in which ER to Golgi transport was blocked by BFA treatment or ATP depletion. In controls, beta COP was associated with Golgi cisternae and transport vesicles as expected. Upon BFA treatment, PAC Golgi cisternae are dismantled and replaced by clusters of remnant vesicles surrounded by typical ER transitional elements that are generally assumed to represent the exit site of vesicular carriers for ER to Golgi transport. In BFA-treated PAC, beta-COP was concentrated in large (0.5-1.0 micron) aggregates closely associated with remnant Golgi membranes. In addition to typical ER transitional elements, we detected a new type of transitional element that consists of specialized regions of rough ER (RER) with ribosome-free ends that touched or extended into the beta-COP containing aggregates. In ATP depleted PAC, beta-COP was not detected on Golgi membranes but was concentrated in similar large aggregates found on the cis side of the Golgi stacks. The data indicate that upon arrest of ER to Golgi transport by either BFA treatment or energy depletion, beta-COP dissociates from PAC Golgi membranes and accumulates as large aggregates closely associated with specialized ER elements. The latter may correspond to either the site of entry or exit for vesicles recycling between the Golgi and the RER. PMID- 8507899 TI - Ca2+ sensitivity of skinned uterine muscle fibers in unilaterally pregnant rats. AB - We prepared chemically skinned uterine muscle fibers from both horns of unilaterally pregnant rats and investigated the effect of gestation on the Ca2+ sensitivity of the Ca(2)-induced contraction. The Ca2+ sensitivity was defined as the pCa (minus logarithm of free calcium concentration) required for half maximum activation of force production. Gravid horns did not show any statistical difference in the Ca2+ sensitivity between normal pregnant and unilaterally pregnant rats. Non-gravid horns of unilaterally pregnant rats before Day 14 of gestation showed the same behavior in the Ca2+ sensitivity as horns of normal pregnant rats. After Day 15 of gestation the Ca2+ sensitivity of non-gravid horn also increased but significantly less than that of gravid horn. Taking into account the hormonal situation, the present results suggest that some local factors, such as an increased size of conceptus (fetus and placenta) and/or intercellular binding conditions of myometrium modulated by the gap junction formation and the appearance of connexin molecules, may also be requisite for the regulation of the contractile activity associated with parturition and delivery of the fetus and placenta. PMID- 8507898 TI - Inositol 1,4,5-trisphosphate mass changes from fertilization through first cleavage in Xenopus laevis. AB - After fertilization in Xenopus laevis, inositol 1,4,5-trisphosphate (IP3) mass increased from 53 to 261 fmol/cell and returned to near basal by 10 min after insemination. IP3 was also elevated over control egg levels during first mitosis and first cleavage. Because IP3 levels and the fertilization calcium wave decline at about the same time and because calcium ionophore or pricking the egg increased IP3, the fertilization calcium wave may be due to calcium-induced IP3 production. In addition, the onset of sperm motility was associated with an increase, whereas the acrosomal reaction was accompanied by a decrease in IP3 mass. Combining our published data with this report, the first chronology of the levels of IP3 from the induction of meiosis (maturation) through fertilization and cleavage in one cellular system is summarized. These data suggest an in vivo dose response for IP3 and calcium release. A small (17 fmol/cell) IP3 change during the induction of meiosis may not be associated with a calcium change. Larger IP3 changes at cleavage (40 fmol/cell) and mitosis (125 fmol/cell) are associated with localized small calcium increases, whereas the largest IP3 change (208 fmol/cell) is associated with the large calcium increase at fertilization. PMID- 8507900 TI - Heterogeneous contractile responses of single smooth muscle cells from guinea pig ileum. AB - Cells of guinea pig ileal longitudinal muscle layer were dispersed by treating the minced tissue with highly purified collagenase and papain. The cells were spindle shaped, 100 to 150 microns long and 5 to 10 microns wide. Contractility of the dispersed cells was determined by "cell adhesion method" resulting that the cells were contracted by carbachol in a dose-dependent manner, but sensitivity and degree of the contraction were different in each cell. Binding assay method resulted that Kd values did not change by treatment with collagenase and papain. These results indicate that contractility of each cell in the tissue is originally different and dispersion of the cells does not affect on the cell contractility. PMID- 8507901 TI - Pathogenesis and animal studies of Parkinson's disease. AB - This article reviews the past year's literature on pathogenesis and animal studies of Parkinson's disease. Studies on aging, genetic aspects, environmental factors, melanin, altered iron metabolism, oxidative stress, defective mitochondrial respiration, excitatory amino acids, and trophic support are reviewed in relation to the vulnerability of dopaminergic nigral neurons and the pathogenesis of Parkinson's disease. PMID- 8507902 TI - Clinical features, diagnosis, and imaging of parkinsonian syndromes. AB - The differential diagnosis of parkinsonian syndromes continues to challenge clinicians. The clinical diagnosis of idiopathic Parkinson's disease is correct in only about three quarters of cases when reevaluated neuropathologically, emphasizing the need for more discriminative diagnostic criteria. The clinical spectrum of brain stem Lewy body idiopathic Parkinson's disease itself may be heterogeneous, including dementing and nondementing, familial and sporadic, and levodopa-responsive and -nonresponsive subgroups. Recent clinicopathologic evidence suggests that other parkinsonian syndromes such as progressive supranuclear palsy may also be neuropathologically heterogeneous. Pharmacologic criteria of dopaminergic responsiveness have no absolute power of differentiating between idiopathic Parkinson's disease and other parkinsonian disorders, although an absent response argues against idiopathic Parkinson's disease. The best diagnostic imaging criteria still come from positron emission tomography studies of the functional integrity of the nigrostriatal dopaminergic system, but more widely applicable techniques are needed. Promising perspectives for this have come form studies of D2-receptor binding with iodobenzamide single photon emission computed tomography in parkinsonian syndromes. PMID- 8507903 TI - Treatment of Parkinson's disease. AB - The treatment of Parkinson's disease is reviewed. The rationale for using selegiline (deprenyl) as the first treatment in recently diagnosed patients is presented. Selegiline delays the need for levodopa; however, it is unclear whether this results from a symptomatic or a neuroprotective effect of selegiline. Levodopa combined with a decarboxylase inhibitor is the principal treatment for patients with moderate or marked symptoms. There is little evidence that levodopa has a deleterious effect on the court of Parkinson's disease. The relationship of levodopa to dyskinesias and response fluctuations is discussed. Pharmacokinetic and pharmacodynamic studies suggest that continuous dopaminergic stimulation may be superior to intermittent pulse therapy. The best approximation to continuous stimulation is the use of long-acting levodopa-carbidopa preparations supplemented by dopamine agonists. PMID- 8507904 TI - Transplantation and surgical treatment of parkinsonian syndromes. AB - Neurosurgical attempts to correct parkinsonism use strategies aimed either at alleviating the underlying dopamine deficiency or at correcting abnormal compensatory effects in neural circuits within the basal ganglia. During the review period, clinical trials of four different neurosurgical approaches were reported. These approaches are intracerebral transplantation of fetal dopamine neurons, intracerebral transplantation of adrenal medullary tissue, tremor reducing surgical lesions in the ventrolateral thalamus, and ventroposterior pallidotomy aimed at reducing akinesia and rigidity. Experimental studies in rats and monkeys designed to explore mechanisms of graft actions were also reported. PMID- 8507905 TI - Dystonia. AB - Dystonia has moved from the status of a rare disease or an uncommon clinical manifestation to the center stage of research in movement disorders. Recent developments have expanded our knowledge of the genetics and understanding of its pathophysiology, and have resulted in significant improvements in the clinical management of this group of disorders. These, as well as the varied and multifaceted phenomenology are reviewed. PMID- 8507906 TI - Choreas, hereditary and other ataxias, tics, myoclonus, and other movement disorders. AB - Developments in the field of Huntington's disease have focused on the potential benefits of predictive testing. Markers have been described for autosomal dominant cerebellar ataxia and for certain subtypes of Friedrich's ataxia. Argentophilic neuronal and glial inclusions appear to be the first specific pathologic hallmark of multiple system atrophy. "Pure" hereditary spastic paraplegia is not a multisystem disorder of the central nervous system, but a monomorphic and stereotyped disease. Advances in Tourette's syndrome are limited because the presumed gene eludes identification. A new type of myoclonus, propiospinal myoclonus, has been described. Clinical and electrophysiologic criteria for defining primary orthostatic tremor have been proposed. Understanding of the neurophysiologic substrate of essential tremor and myoclonus is improving. New neurologic disorders presenting clinically with prominent movement disorder continue to be described. PMID- 8507907 TI - Dysmyelinating and demyelinating conditions in infancy. AB - The myelin membrane is essential for rapid conduction of nerve impulses through the central nervous system. Failure of myelination--dysmyelination--may arise through several mechanisms. The synthesis of a particular myelin protein can be defective, as occurs for proteolipid protein in Pelizaeus-Merzbacher disease and for myelin basic protein in the 18q- syndrome. Delay in myelination with a more generalized diminution in white matter is characteristic of many inherited metabolic diseases, including galactosemia, pyridoxine-dependent seizure disorder, glutaric aciduria type 1, and infantile Refsum disease. Demyelination or breakdown in myelin is characteristic of metachromatic leukodystrophy, Krabbe disease, mitochondrial disorders, adrenoleukodystrophy, Canavan disease, Alexander disease, and orthochromatic leukodystrophy. A fourth category is reserved for malformation syndromes. These include Cockayne, Fukuyama, Walker Warburg, and Angelman syndromes. Demyelination also occurs in HIV-infected individuals with central nervous system findings and in multiple sclerosis. Much of the evidence for leukodystrophy in these disorders comes from neuroimaging. Some of these disorders are treatable. PMID- 8507908 TI - Extrapyramidal disorders in childhood. AB - The term extrapyramidal system originally referred to the system concerned with motor function other than the pyramidal tract. This review covers papers that concern the basal ganglia and related structures except disorders relating to the cerebellum. Because the pathophysiologies of these disorders remain unknown, I review those papers that focused or implicated these points. PMID- 8507909 TI - Normal and abnormal patterns of myelin development of the fetal and infantile human brain using magnetic resonance imaging. AB - Magnetic resonance imaging allows a noninvasive assessment of myelination during normal brain maturation as well as the detection of genetically determined and acquired diseases that affect the synthesis and maintenance of myelin. If this high sensitivity of magnetic resonance imaging for white matter changes is completed by adequate clinical and biochemical information, a unique diagnostic tool is available to gain new insights in the formation of myelin and pathogenesis of myelin disorders. PMID- 8507910 TI - Strategies for diagnosis and treatment of childhood epilepsy. AB - Recent developments in neuroimaging have advanced our capability to diagnose and perform presurgical evaluations in a large proportion of children without recourse to invasive monitoring techniques. Functional imaging is also providing us with novel insights into the mechanism of certain childhood epileptic syndromes. The role of anatomic (computed tomography, magnetic resonance imaging) and functional (single photon emission computed tomography, positron emission tomography) imaging modalities in the diagnosis and therapeutic decision making in major epileptic syndromes of childhood is reviewed. PMID- 8507911 TI - Bacterial meningitis and Lyme neuroborreliosis in childhood. AB - Neurologic infections represent a major problem in child neurology. Recent research on this issue has had important implications for diagnosis and pathophysiology of infectious diseases of the child's brain, resulting in new therapeutic approaches. A better understanding of the molecular pathophysiology of bacterial meningitis has developed, and therapeutic interventions focus on the host's inflammatory response. Therapeutic trials with dexamethasone in addition to antibiotic treatment have yielded promising results in reducing morbidity and long-term neurologic sequelae in bacterial meningitis. The detection of Lyme borreliosis in 1977 substantially influenced the differential diagnosis of inflammatory central nervous system diseases. Lyme neuroborreliosis proved a main cause of acute peripheral facial palsy and aseptic meningitis in children. An effective antibiotic treatment has become available for a large number of patients with these illnesses. PMID- 8507912 TI - Neurologic consequences of hypoglycemia and pathogenic mechanisms involved in diabetic neuropathy. AB - Although the limitations of human experimental models of hypoglycemia have hampered investigation, it is generally accepted that a reversible deterioration in cognitive function occurs at a plasma glucose concentration of around 3.5 mmol/L, above the glycemic threshold for symptoms. It is unclear whether this threshold varies in those with hypoglycemia unawareness. Repeated severe hypoglycemia may cause chronic impairment although the clinical significance and the contribution of other factors remains unclear. There is increasing evidence that microvascular abnormalities are the major factor in the pathogenesis of peripheral neuropathy. This may be why there is still little experimental support from human clinical studies for the use of aldose reductase inhibitors in its treatment. PMID- 8507913 TI - Neurologic complications of inherited mitochondrial abnormality, and neurologic consequences of inborn errors of metabolism. AB - The possibility of gene therapy for patients with Menkes or Gaucher's disease has been improved by the isolation of a promising candidate gene and production of a mouse model, respectively. Many mutations of mitochondrial DNA are being associated with mitochondrial encephalomyopathies, and protection of the resultant biochemical deficiency can be achieved with a remarkably low percentage of normal mitochondrial DNA. The correlation between mutation, biochemical deficiency, and neurologic consequence, however, remains frustratingly obscure. Gas chromatography-mass spectrometric urinalysis is becoming increasingly important in the diagnosis of metabolic disorders and is revealing new and unexpected deficiencies. PMID- 8507914 TI - Environmental neurotoxicity of chemicals and radiation. AB - Epidemiologic and societal concerns continue to stimulate studies in the field of environmental neurotoxicology. Although the role of heavy metals, aluminum, and iron are unclear in the etiology of human neurodegenerative disorders, these toxins have provided fertile ground for in vivo and in vitro experimental studies to elucidate their role in neurotoxic injury. Experimental models of clinical syndromes are discussed with special relevance to developmental neurotoxicology. Cycloleucine, tellurium, and 1,3-dinitrobenzene provide models of subacute combined degeneration, primary peripheral nerve demyelination, and thiamine deficiency-like lesions, respectively. Increasing attention is being given to irradiation neurotoxicity, especially in the developing or young central nervous system. A fuller understanding of the pathogenesis of low-dose irradiation injury allows for a clearer understanding of its neurobiology and also provides a more rational approach to understanding an interventional therapy associated with brain irradiation for childhood neoplasia. PMID- 8507915 TI - Alcohol- and drug-related neurotoxicity. AB - The nervous system is vulnerable to a wide range of toxic insults. Historically, the toxic syndromes most often encountered have involved drugs of abuse, most notably alcohol. Cocaine has also been securely identified in recent years as neurotoxic. Equally distressing are neurotoxic disorders resulting from the administration of drugs for other conditions, and a growing literature is documenting these effects as well. This review discusses the cerebral basis of drug abuse and then considers recent data on the neurotoxicity of ethanol, methanol, and cocaine. Finally, selected examples of iatrogenic drug effects illustrate the variety of toxic syndromes that can occur with commonly employed treatment modalities. PMID- 8507916 TI - The use of toxins to elucidate neural function and disease. AB - In some cases, toxins can be useful tools to produce models of human disease. This is especially so with neurotoxins, which have been used to simulate disease in both the central and peripheral nervous systems. However, it is important to be cautious in extrapolating the biochemical consequences of the toxins to the respective human disorder. In this respect, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine has proved to be of particular value and has provided many important clues in the search for the cause of Parkinson's disease; this review focuses on recent advances in our understanding of its mechanism of action. PMID- 8507917 TI - Movement disorders. PMID- 8507918 TI - Pediatric and developmental neurology. PMID- 8507919 TI - Metabolic disorders and neurotoxicology. PMID- 8507920 TI - Two-year follow up on the protective value of dust masks against farmer's lung disease. AB - Some advocate moving away from the farm environment for farmers affected with farmer's lung disease (FLD), but most affected farmers still live on farms. In this study, we evaluated the practicality of dust masks and their effectiveness in prevention of FLD. The dust masks we chose were practically used and no new severe episodes of FLD developed in 20 of 21 farmers with FLD using the masks during a 2-year period. When the farmers took off the dust masks in a farming environmental provocation test, statistically significant reductions in FVC (mean 3.43 to 3.351, p < 0.01), DLco (mean 19.6 to 18.2 ml/torr/min, p < 0.01), and DL/VA (mean 5.1 to 4.8 (x10(-3)) 1/torr/min, p < 0.01) were observed several hours after exposure. These findings suggest that the dust masks were used practically during routine dairy farming and were effective in protection against FLD. PMID- 8507921 TI - Prognostic implications of plasma levels of atrial natriuretic factor in patients with acute myocardial infarction. AB - Several neurohormonal factors have been proposed as markers of the severity of acute myocardial infarction (MI). To determine whether plasma concentrations of atrial natriuretic factor (ANF) might predict post-MI prognosis, we studied 130 patients with acute MI (97 males and 33 females, mean age 62 years). Within one half to one day after admission, a blood sample was taken for estimation of circulating ANF. The mean follow-up period was 37 months, and the follow-up rate was 97%. Of the 130 patients, 28 died from cardiac causes during the follow-up period. Patients were classified into three groups according to plasma ANF levels (group 1, < 99 pg/ml; group 2, 100-199 pg/ml; group 3; > 200 pg/ml). The survival curves were constructed by the Kaplan-Meier method. There were significant differences in the cumulative survival rate among the three groups (group 1 > group 2 > group 3; p < 0.001). The baseline characteristics (age, atrial pressure, and cardiac index) were different among the groups, therefore these variables were analyzed by a Cox multiple regression model. Significant predictors of cardiac mortality were plasma ANF class (p < 0.002) and pulmonary capillary wedge pressure (p < 0.007). In conclusion, these observations demonstrated that stratification of acute MI patients by plasma ANF level is a useful non-invasive method for predicting prognosis and for identifying individuals at high risk of cardiac death. PMID- 8507922 TI - Pure progressive autonomic failure presenting severe orthostatic hypotension. AB - A 59-year-old woman showed chronic progressive autonomic failure consisting of orthostatic hypotension and dyshidrosis. No signs of Parkinsonism, cerebellar or peripheral neuropathy were observed. Autonomic nervous function tests and findings of biopsied sural nerve suggested that this case had both sympathetic and parasympathetic dysfunctions, mainly postganglionic. A decrease in the total peripheral resistance and no increase in the heart rate on standing seemed to be the mechanism of orthostatic hypotension in this case. We conclude that pure PAF can be recognized as a distinct clinical syndrome of systematic degeneration of the autonomic nervous system. PMID- 8507923 TI - A diabetic case of Hb Riyadh with a low HbA1c value. AB - A 74-year-old male patient with diabetes mellitus and hypertension who had been treated for a long period was admitted to our hospital. Laboratory data on admission revealed high values for fasting blood sugar and fructosamine, 219 mg/dl and 389 mumol/l respectively, while the concentration of glycated hemoglobin (HbA1c) was low (3.0%). High performance liquid chromatography and isoelectric focusing analysis of the patient's Hb disclosed abnormal Hb with the content being 41.3%. The structural analysis indicated that this abnormal Hb was Hb Riyadh [beta 120 (GH3) Lys-->Asn]. The low value of HbA1c despite the high blood glucose level may be attributed to this abnormal hemoglobin. PMID- 8507924 TI - Congenital nephrogenic diabetes insipidus in an adult. AB - A 35-year-old man with congenital nephrogenic diabetes insipidus (NDI) is reported. Renal biopsy revealed miniaturized and rounded mitochondria of the proximal tubular cells and decreased brush-borders. Trichlormethiazide combined with triamterene resulted in an apparent reduction of daily urine volume and concomitant increment in urine osmolarity. The present case seems rare in that some morphological changes in the renal tissues could be demonstrated in an adult case with congenital NDI. PMID- 8507925 TI - Malignant lymphoma with myxoid change and sarcomatous features. AB - We report a case of unusual B-cell malignant lymphoma of the kidney and mediastinum. Renal biopsy showed prominent myxoid changes and sarcomatous features, leading to considerable difficulty in histologic diagnosis on routinely stained histologic sections. However, immunohistochemical staining for lymphocyte markers led to the final histologic diagnosis of B-cell malignant lymphoma. Although myxoid change is not generally found in malignant lymphoma, malignant lymphoma should not be excluded from consideration when one encounters a small round cell sarcoma with myxoid stroma, especially in extranodal soft tissue tumors. PMID- 8507926 TI - Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney. AB - A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease. PMID- 8507927 TI - Immunoglobulin-complexed aspartate aminotransferase. AB - We report a case of increased aspartate aminotransferase (AST, EC 2.6.1.1; GOT) in a 17-year-old girl which persisted for 3 years. The patient was healthy, but a high level of serum AST was detected during a school health check. Further examination revealed that AST was increased to as high as 259 IU/l while alanine aminotransferase (ALT) was normal. Immunoelectrosyneresis and immunoprecipitation methods revealed that this atypical AST combined with IgG--kappa, lambda globulin and formed macromolecular complexes. Including the present case, 26 cases of IgG complexed AST have been reported. It is important to be aware of this syndrome, and thereby avoid unnecessary examinations and therapies. PMID- 8507928 TI - Adrenal myelolipoma: comparison of diagnostic imaging and pathological findings. AB - Myelolipoma of the adrenal gland is a rare, benign, nonfunctioning lesion consisting of fat and bone marrow elements in varying proportions. This tumor is commonly asymptomatic and usually discovered during various diagnostic imaging examinations performed for unrelated diseases. If a primary malignant or metastatic adrenal tumor cannot be excluded, ultrasound- or computed tomography guided needle biopsy of the tumor is necessary. We report a case of adrenal myelolipoma associated with advanced gastric carcinoma and compare the diagnostic imaging findings with the pathological findings of the adrenal myelolipoma. PMID- 8507929 TI - Nephrotic syndrome with massive accumulation of type I and type III collagen in the glomeruli. AB - A 54-year-old woman with nephrotic syndrome underwent renal biopsy. By light microscopy, the glomerular capillary lumen was remarkably narrowed because of diffuse accumulation of Periodic acid Shiff (PAS) positive material along the glomerular capillary wall. By electron microscopy, collagenous fibers were observed in the mesangium and subendothelial area. The fibrous material reacted with antibodies against type I and III collagen but not with those against laminin or type IV collagen by an indirect immunofluorescence technique. This case seemed to be a case of collagenofibrotic glomerulonephropathy. PMID- 8507930 TI - Sinus and atrioventricular nodal re-entrant tachycardia. AB - A case of a 42-year-old woman who had combined sinus and atrioventricular nodal tachycardia is reported. Programmed atrial stimulation study showed the induction of the two types of paroxysmal supraventricular tachycardia. The mechanisms of these supraventricular tachycardias were both sinus nodal and atrioventricular re entrant tachycardia. Sinus nodal re-entrant tachycardia could be induced only after injection of atropine. The tachycardias could no longer be induced after the administration of verapamil. PMID- 8507931 TI - Erythroderma and marked atypical lymphocytosis mimicking cutaneous T-cell lymphoma probably caused by phenobarbital. AB - A 56-year-old man had been treated with phenobarbital seven weeks prior to admission. One month after initiation of administration of phenobarbital, fever, skin rash and lymphadenopathy occurred. Nine days later, marked atypical lymphocytosis, eosinophilia and hepatic injury was noticed. The histology of the biopsied skin was indistinguishable from lymphoma. CHOP-therapy was started but the patient was followed without further treatment because of polyclonal T lymphocytosis. Afterward, clinical and hematologic improvement ensued and he has been well until now, 52 months later. The marked T-lymphocytosis observed in this case is probably a lymphoid leukemoid reaction secondary to hypersensitivity to phenobarbital. PMID- 8507932 TI - Intramural rupture of the esophagus: a rare complication associated with nasobiliary catheter placement. AB - Intramural rupture of the esophagus developed after short-term nasobiliary catheter placement in an 87-year-old female with choledocholithiasis and suppurative cholangitis. Endoscopy revealed bleeding accompanied by circumferential disruption of the mucosa along the lower third of the esophagus. Withdrawal of the catheter and conservative treatment resulted in recovery of the lesion and relief of symptoms. This rare complication should be kept in mind during the placement of nasobiliary catheter. PMID- 8507933 TI - Distinct responses of interleukin-6 and other laboratory parameters to treatment in a patient with Wegener's granulomatosis. AB - We describe a patient with Wegener's granulomatosis in whom the serum levels of interleukin-6 (IL-6) and other laboratory parameters were monitored. The IL-6 and CRP levels, which were extremely high before treatment, declined rapidly with corticosteroid and cyclophosphamide. IgG, leukocyte count and platelet count declined more gradually. Thus, determination of the serum IL-6 level might be useful in diagnosing and monitoring Wegener's granulomatosis. PMID- 8507934 TI - Transitions in the patterns of infections and countermeasures. PMID- 8507935 TI - EEG changes during mental calculation, reverse recitation and association exercises in patients with dementia of the Alzheimer type. AB - The cerebral functional impairment in dementia of the Alzheimer type (DAT) was a quantitatively assessed using easily repeatable electroencephalographic analysis. Waveform recognition was employed to analyze the EEG (electroencephalogram) changes displayed before and after tasks of mental calculation, reverse recitation and mental association. Marked decrements in the incidence of theta and alpha waves together with decrements of the average amplitude of alpha waves were noted in normal elderly subjects after mental calculation and reverse recitation. In the patients with DAT, mental association tasks evoked pronounced decrements in the average amplitude of theta waves, the average frequency of alpha waves, and both the average frequency and average amplitude of beta waves. These results indicate that analysis of EEG activity responses to mental tasks provides an objective assessment of dementia. PMID- 8507936 TI - Genetics and obstructive sleep apnea syndrome: a study of human leukocyte antigen (HLA) typing. AB - To investigate the possible influence of genetics in subjects with obstructive sleep apnea syndrome (OSAS), HLA-A, B, C, and DR antigens were studied in 32 Japanese subjects with OSAS. The frequency of HLA-A2 antigen was markedly increased in the patients with OSAS compared with normal controls (81.3% vs 40.6%) and compared with the Japanese population (40.7%), Pc < 0.035 and Pc < 0.007, respectively. HLA-B39 was found more frequently in OSAS patients than in the Japanese population (Pc < 0.018), but not in the controls. No significant deviation was observed in the frequencies of HLA-C and DR antigens between the OSAS patients and the controls. We conclude that genetics is important in the development of OSAS. PMID- 8507937 TI - Immunoblot analysis of Aspergillus fumigatus antigen with human antibodies and lectin probes. AB - Components of culture filtrate antigen of Aspergillus (A.) fumigatus were electrophoretically separated, transferred to hydrophobic durapore membrane, and then probed with patients' sera and lectins. Using human sera from patients with aspergilloma and allergic bronchopulmonary aspergillosis (ABPA), more than 13 IgG binding components were identified. IgG binding to high molecular weight components (HMW) of over 30 kDa was observed in all patient sera tested, but IgG binding to low molecular weight components (LMW) of approximately 18 kDa was observed in 7 out of 8 patients' sera which showed a positive precipitin reaction by means of counterimmunoelectrophoresis. Concanavalin A and lens culinaris agglutinin showed strong binding to HMW but no binding to LMW. Further, strong IgE binding to the 18 kDa component was observed in serum from a patient with ABPA during the acute stage, but not during the convalescence stage. It is suggested that the 18 kDa protein from A. fumigatus is the primary antigen in the serological antibody responses observed in patients with aspergilloma or ABPA. PMID- 8507938 TI - Managing change. AB - Much is written about the nature of change, and more is said about the effects of change on people and organisations, but little is offered to those struggling to manage change. Support may seem especially thin for managers in the demanding environment of a modern operating department. PMID- 8507939 TI - Day surgery in Bristol. AB - As in the rest of the United Kingdom, day surgery in Bristol is on the increase. In the Bristol Royal Infirmary day surgery unit (DSU) we treat approximately 3,500 patients a year. We have recently opened a second operating theatre. This has shifted the proportion of cases from our general theatres. This has also improved our case mix, less minor surgery under local anaesthetics, to more of the recommended 'basket type' surgery ie hernia repair, varicose vein surgery, excision of breast lumps etc. We have recently introduced an appointment booking system that is progressing. Such changes have to be introduced with good preparation, communication and a lot of diplomacy. I would like to outline the management aspects that help to expand and improve on the service we give, including patient selection and the appointment booking system we have introduced. I will describe how we drew up a policy involving the organisation of operation lists and staff involvement in day surgery management and accountability for patient care from admission through to discharge including our latest care plan. Finally I will outline the methods we have developed for evaluating the care we give. PMID- 8507941 TI - Reflections--tradition? PMID- 8507940 TI - New law--old habits. Study day report. AB - In his introduction to a study day, entitled 'Work Injuries--New Law, Old Habits'. Phil Gray, labour relations director of the RCN, described the background of the potentially alarming rise in reported back injury amongst nurses--1.5 million days per year are lost for this reason. In 1991 an RCN survey found back injury to be an ongoing problem, with a lack of training, assessment or proper care. PMID- 8507942 TI - The paucity of care for the mentally ill. PMID- 8507943 TI - African diary. PMID- 8507944 TI - Mentorship in critical care. AB - In line with Project 2000, the development of core-curriculum based training in post-basic education has led to changes in assessment strategies. The Critical Care core-curriculum with its reduced time span of only six months has meant that specialist input is reduced. The time span for each branch has almost halved that of the traditional ENB 176 course. The students spend eight weeks in the classroom leaving only 16 weeks for practice. As a result, it becomes very important to have an effective mentoring programme. This article looks at the mentoring dimension in post registration common core courses. It defines the term as used, and outlines factors which influence an effective mentoring programme as well as suggesting some ways which may help mentors maintain this role. PMID- 8507945 TI - The cervical smear. A simple test can save a woman's life. AB - Every year more than 2,000 women die from cervical cancer, at least 30% of those have never had a smear test, more than 80 out of 100 women who are treated are completely cured. A test which involves a doctor taking a sample from the neck of the womb (cervix), a smear test, can detect if there are any abnormalities of the cervix which might develop into cancer. A test which if positive does not always mean cancer. A test which every sexually active woman requires from the age of 16 64. A test which is needed at least every three years of a woman's life. PMID- 8507946 TI - Breast cancer--one nurse's experience. Interview by Kate Nightingale. AB - The government paper 'The Health of the Nation' targets the prevention of certain types of cancers as one of its main priorities. It states that the best chance of saving lives lost to breast and cervical cancer is the screening programmes already in place and that encouraging more women to take part in these programmes could save over 2,500 lives a year. This article is about one woman's experience of breast cancer both as a practice nurse and as a patient. Pamela agreed to be interviewed to describe what it was like to suddenly find yourself on the other side of the fence. PMID- 8507947 TI - Sustaining professional practice: an overview of opportunities. AB - Over the last decade the trend in surgical nursing has been towards more involvement of the patient in care and decision-making. The ideology of the nursing process can enable the family and the patient to become involved and to exercise individual rights. Within the framework of the nursing process the nurse has been encouraged to perceive and relate to patients in terms of their common and particular personal needs. Furthermore, the patient has a right to contribute to the decision-making process. From the patient's perspective this has been a welcomed change. In recent years patients' rights movements and the development of patients' charters within hospitals and health authorities have been focal. From the nurses' perspective this means that the patient has a right to challenge decisions and treatment. This in turn may lead to nurses' examining and questioning standards of care and professional accountability. PMID- 8507949 TI - Endoscopic surgery. PMID- 8507948 TI - Environmentally friendly. PMID- 8507950 TI - Acute postoperative pain: logical treatment by drug combinations. AB - Most patients who undergo major surgery suffer severe postoperative pain. This fact has been known by many generations of health care workers, and highlighted in the report of the Working Party organised jointly by the Colleges of Surgeons and Anaesthetists of Great Britain. Although effective therapies exist they are frequently not used in an effective manner. Everyone knows that enough morphine will abolish pain. However, the doses of a drug such as morphine required to completely relieve a patient's pain may cause several side effects or even death. There is an enormous variability between patients and operations in morphine requirements to relieve postoperative pain. Many patients are not given adequate doses for fear of inducing side effects. It is obvious that provision of postoperative pain relief tailored to each individual patient's needs requires more than a 'prn Omnopon' prescription. The level of pain needs to be monitored in much the same way as we would monitor blood pressure or urine output postoperatively and health workers who understand these readings and the appropriate treatment should review them. PMID- 8507951 TI - Hazards and safety in theatre. AB - The Health and Safety at Work Act (1974) provides legislation aimed at securing the safety of everyone at their place of work, and of any other person whose safety may be at risk by their presence in that area. Responsibility rests at all levels. Management have a duty to provide a safe working environment and to provide education and training for workers. At a departmental level daily safety checks need to be carried out and continuous safety conscious management must be in evidence. At a personal level we must all work carefully, bearing in mind the particular hazards in our area to ourselves, to our colleagues and our patients. This article hopes to highlight some of the trouble spots we should already be familiar with. PMID- 8507952 TI - Reflections--some hazards in anaesthesia. PMID- 8507953 TI - 2% activated glutaraldehyde. PMID- 8507954 TI - Manual handling--a review of the new legislation. AB - There can be no doubt that one of the greatest hazards that a nurse faces during the course of his or her career is the manual handling of patients. Of the 4,580 handling accidents that were reported to the Health and Safety Executive (HSE) in 1990, 70% of them involved the handling of patients. The dangers of manual handling were acknowledged in the 1961 Factories Act and the 1963 Offices, Shops and Railway Premises Act, both of which stated, 'No person shall be employed to lift a load so heavy as to be likely to cause injury to him.' This statement was, however, too broad. It was difficult to interpret. What is so heavy as to be likely to cause injury? This problem of interpretation also made enforcement troublesome. PMID- 8507955 TI - Accreditation in nursing education. An explanation. AB - It has long been recognised that the provision of continuing education for nurses, midwives and health visitors is often ineffective and sporadic in its delivery. Some courses are recorded with the National Board but others, often of equal value, are merely statements of attendance or 'in-house' courses with no formal assessment, repeated at the same level and on different courses, creating repetition and failing to maximise opportunities for career development. In addition, no recognition of expertise gained in the workplace has been considered. Many practitioners have, as a result, felt devaluated when their years of practice are granted no formal recognition. PMID- 8507956 TI - What is a HISS? Hospital Information Support System. AB - A HISS is a Hospital Information Support System and the idea is that it is primarily there to support clinical activity not to provide management information. When the concept of a HISS first emerged it was seen as a very large system where all hospital departments shared one computer system and that is the model used by the first few HISS sites. As the Health Service has changed and the difficulties of replacing all the computer systems in a hospital with one large system have been appreciated, so the concept of HISS has developed. We now talk about an incremental approach to HISS. This means looking at the present systems and deciding which ones should be retained and 'interfaced' with the new system. No system is the best for every department and this approach allowing 'foreign' systems to be attached to the main system (usually centred on the Patient Administrative System) does provide a good fit with the needs of the department. This does not need to be implemented immediately but can be introduced at the end of the life of an existing system, thus protecting the past investment in systems. PMID- 8507957 TI - Some appalling stereotypes. PMID- 8507958 TI - Short stay care centre. PMID- 8507959 TI - Great expectations? Reflections.... PMID- 8507960 TI - Amber: all change. PMID- 8507961 TI - Pre-operative starvation of the neurosurgical patient. PMID- 8507962 TI - Cavity dressings ancient and modern. A little research. PMID- 8507963 TI - An alternative surgical technique in orthotopic cardiac transplantation. AB - Forty patients underwent orthotopic cardiac transplantation at Wythenshawe Hospital between May 1991 and November 1992. Twenty patients had transplantation using an alternative technique that preserves the shape of the left atrium and leaves the right atrium intact (group A). The remaining twenty had conventional transplantation using the technique described by Lower and Shumway (group B). The patients were randomized to either the new or the conventional technique on an alternate basis. There was no mortality in group A, but two patients in group B developed right ventricular failure and died. Two patients in each group developed nodal rhythm and all four recovered sinus rhythm. Echocardiography and Doppler velocimetry at the transvalvular level confirmed normal atrial function in group A with erratic atrial contraction wave in group B. There was also slightly lower incidence of mitral and tricuspid valve regurgitation in group A than in group B. The improved atrial function in group A may play a part in the prevention of right sided failure following cardiac transplantation. PMID- 8507964 TI - Aortic valve replacement and mitral valve repair with allograft. AB - Techniques of repair of defects in the anterior leaflet of the mitral valve and replacement of the aortic valve using allograft are presented. The case history and operative procedure of a reconstructive operation that did not require anticoagulant therapy after surgery are described for three adult patients. Mitral valve defects were repaired using the anterior leaflet of the mitral valve of the allograft. The aortic valve or entire root was replaced with the aortic allograft. The aortic/mitral allograft should be considered as an alternative to replacement of the aortic and mitral valves with prostheses in selected patients. PMID- 8507965 TI - Creation of a systemic-to-pulmonary artery shunt by use of an internal mammary artery. AB - The creation of a systemic-to-pulmonary artery shunt by use of the internal mammary artery (IMA) in a 2-year-old boy with complex congenital heart defects and diminutive pulmonary arteries is described. This procedure may offer advantages over standard methods in selected patients with extremely small pulmonary arteries. The pliability, favorable anatomical position, and growth capability of the IMA reduce chances for complications, such as stenosing, kinking, and stretching of the pulmonary artery, which can cause it to become distorted, making further definitive repair difficult. PMID- 8507966 TI - Left atrial plication and mitral valve replacement for giant left atrium accompanying mitral lesion. AB - Between January 1982 and November 1992, 38 patients received simultaneous mitral valve replacement (MVR) and left atrial plication (LAP) because of giant left atrium accompanying mitral lesion. Their ages ranged from 33 to 70 years, and the mitral lesion was caused by rheumatic heart disease in all patients. MVR was performed with a St. Jude Medical prosthesis for all patients and the left atrial wall was plicated with running 3-0 Nespolene to reduce the width to 3 to 5 cm. Respiration requiring mechanical ventilation more than 48 hours after operation occurred in four patients (10.5%) and postoperative low cardiac output requiring a high dose of dopamine HCl or intraaortic balloon pumping in nine patients (23.7%). The left atrial diameter measured by echocardiogram was a mean of 7.3 +/ 1.0 cm before operation and 5.8 +/- 1.0 cm postoperatively. The cardiothoracic ratio on the chest roentgenogram registered a preoperative mean of 73.3% +/- 9.8% and was 65.7% +/- 8.4% after operation. The pre- and postoperative values were significantly different (p < 0.01). The postoperative exercise level was a mean of 5.3 metabolic units for 24 patients and the postoperative New York Heart Association functional classification indicated Class I or II for 37 patients with no evidence of left atrial thrombus except in the case of one early death. LAP with MVR for patients with giant left atrium due to mitral lesion appeared to result in improvement in respiratory and circulatory functions. PMID- 8507967 TI - Long-term follow-up after two coronary repair of anomalous left coronary artery from the pulmonary artery. AB - A retrospective analysis of ten patients with anomalous left coronary artery arising from the pulmonary artery operated between 1979 and 1990 was undertaken. All presented with evidence of left ventricular dysfunction and "ischemic" mitral regurgitation. Surgical repair consisted of an aortopulmonary tunnel (Takeuchi) procedure in eight and direct left coronary artery reimplantation in two. Two patients required postoperative support with a left ventricular assist device. There were no operative or late deaths (CL 0% to 17%) for a follow-up of over 670 patient months. All patients are in New York Heart Association Class I or II, though two patients are still receiving anticongestive medications. One patient has required further surgery for pulmonary artery stenosis, and another has had a mitral valve replacement because of severe mitral regurgitation. One additional patient has moderate-to-severe residual mitral regurgitation and two have a trivial left coronary to main pulmonary artery fistula. All have a patent, nonstenotic left coronary artery and much improved left ventricular function and perfusion as assessed by echocardiography, thallium scan, gated blood pool scan, and angiography. There have been no documented arrhythmias, clinically or on Holter monitoring. The ECGs have shown resolution or improvement of the initial changes of ischemia/infarction in all patients. Chest X-rays have shown normalization of cardiothoracic ratio in eight of ten patients. Excellent early and late results can be achieved following timely surgical repair. Marked improvement in left ventricular function has been observed in patients with poor preoperative left ventricular function, even in the presence of extensive ischemia/infarction. PMID- 8507968 TI - Risk stratification in unstable angina: how to select patients who need emergency revascularization. AB - Patients considered to have unstable angina have a varying prognosis depending on their clinical presentation. Prognosis can be influenced by several factors including persistent pain, transient ST segment shifts, left main coronary artery stenosis, and silent myocardial ischemia. Most patients who present with unstable angina have their symptoms controlled initially with pharmacological management. If symptoms persist, coronary angioplasty or heart surgery can be performed but morbidity and mortality is slightly higher than in patients who are stable. Patients who will benefit from early revascularization include those with persistent myocardial ischemia as manifested by spontaneous angina, spontaneous ST segment shifts on ambulatory ECG, a positive exercise test at a low cardiac workload, or a markedly positive radionuclide or cardiac ultrasound imaging test. PMID- 8507969 TI - Early recollections of Dr. John H. Gibbon, Jr. PMID- 8507970 TI - The heart: location of the human soul--site of surgical intervention. AB - Over millennia, the heart has played an important role in philosophy, medicine, literature, art, and theology. Most cultures consider the heart to be the location of the soul or mind, the "center" of the human body. Modern natural sciences, however, downgrade it to a mere organic blood pump and, simply, a site of surgical interventions. Dealing with this central organ of the body, cardiac surgery is a royal discipline among the medical professions and is highly respected by the public. PMID- 8507971 TI - Blood-surface interactions during cardiopulmonary bypass. AB - The interaction between blood and the synthetic surfaces of the heart-lung machine activates plasma protein systems and blood cells to produce a host of vasoactive substances that mediate the "whole body inflammatory response" associated with cardiopulmonary bypass (CPB). Plasma proteins are instantaneously adsorbed onto nonendothelial surfaces; plasma factor XII is cleaved into two serine proteases; and platelets are activated to aggregate, adhere to adsorbed fibrinogen, and release granule contents. Activation of factor XII initiates coagulation by the intrinsic coagulation pathway and activates complement. Complement stimulates neutrophils to release vasoactive and cytotoxic substances. Endothelial cells, perhaps stimulated by formation of minute quantities of thrombin, produce tissue plasminogen activator, which generates plasmin, a fibrolytic enzyme. Blood becomes a stew of powerful enzymes and chemicals that alters vascular smooth muscle and endothelial cell contraction. Capillary permeability increases, fluid is retained, and function of essentially every organ is temporarily impaired. Attempts to control the morbidity of CPB have focused on reversible inhibitors of specific reactions in blood. Prostanoids and new disintegrins are promising platelet inhibitors that are reversible. Aprotinin and other serine protease inhibitors partially control fibrinolysis and activation of neutrophils. Alternatives to heparin also show promise. Eventually control of the interaction of blood and synthetic surfaces will control the adverse reactions of the heart-lung machine and reduce the bleeding, thrombotic and inflammatory complications of open heart operations. PMID- 8507972 TI - Long-term results of pacemaker therapy after orthotopic heart transplantation. AB - The objectives of this study were to identify: (1) the indications for pacemaker implantation; (2) the long-term survival; (3) the percentage of bradyarrhythmias below 50 beats/min persisting for more than 3 months; and (4) the variables predicting persistent bradyarrhythmias following orthotopic heart transplantations. During the recent decade (August 1, 1981 through December 31, 1991), 237 patients underwent orthotopic heart transplantation at our institution. Twenty-six recipients (11%) showed evidence of a symptomatic bradyarrhythmia due to sinus node dysfunction (n = 25) or complete heart block (n = 1), which required insertion of a permanent pacing device. During a mean follow up period of 17.2 months (range 3 to 57 months), five patients (19%) died and one was lost to follow-up. Actuarial survival at 1 and 4 years were 81% and 65%, respectively, as compared to 79% and 69%, respectively, in patients without permanent pacemakers. Holter monitoring after 3 months (n = 25) and 1 year (n = 14) showed a spontaneous heart rate below 50 beats/min in six (24%) and three patients (18%), respectively. None of the tested variables predicted the necessity of initial pacemaker implantation. However, in patients requiring permanent pacing for a period longer than 3 months, ischemic time of the donor heart was found to be significantly longer as compared to the other patients (221 +/- 76 min vs 137 +/- 91 min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507973 TI - Normal AV node function in patients with sinus node dysfunction after cardiac transplantation. AB - Postoperative atrioventricular nodal (AVN) function was compared in 55 patients with normal and 50 patients with impaired sinus node (SN) function after cardiac transplantation (corrected SN recovery time > 520 msec or sinus arrest +/- escape rhythm). Fifty-two patients had fixed atrial pacing at cycle lengths between 600 and 430 msec, and 53 patients at cycle lengths from 600 to 300 msec between postoperative weeks 1 to 3. Relative (stimulus-R interval; AVNRRP) and effective AVN refractory period (AVNERP) were determined in 53 patients at a cycle length of 500 msec. Only one of 105 recipients had high degree AVN conduction disturbance characterized by a Wenckebach phenomenon at cycle length < 630 msec in the first postoperative week. Three patients with normal and two patients with impaired SN function had Wenckebach cycle lengths > 430 msec while the Wenckebach cycle lengths were < or = 430 msec in the remainder (p = NS). Resting PQ interval (146 +/- 18 vs 162 +/- 32; p = 0.09), Wenckebach cycle length (350 +/- 53 vs 362 +/- 50 msec), AVNRRP (356 +/- 38 vs 367 +/- 37 msec), and AVNERP (217 +/- 48 vs 244 +/- 49 msec) did not differ significantly between patients with normal and impaired SN function. AVN conduction did not deteriorate during 318 +/- 130 days of follow-up (PQ at follow-up 154 +/- 17 and 158 +/- 22 msec, patients with normal and impaired SN function, respectively). One DDD pacemaker was placed for AVN conduction disturbance while 22 pacemakers were implanted for SN deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507974 TI - Circulatory assist techniques in cardiogenic shock: metabolic aspects. AB - Assisted circulation in severe cardiogenic shock was evaluated using a reservoir and a single pump without an oxygenator in 88 dogs. Study groups included: no treatment, substrates only (cysteine, ribose), nitroprusside, left ventricular (LV) + right atrial (RA) bypass + substrates, LV + RA bypass, left atrial (LA) + RA bypass, LA bypass, LV bypass, LV + RA + fluosol. Metabolic studies of O2 consumption, acid and alkaline phosphatase, lactate, creatine phosphokinase (CPK), myocardial depressant factor (MDF), and tissue adenosine triphosphate (ATP) were done in the course of 4-hour treatment periods followed by 2-hour observation periods. Best survival at 4-hour and 6-hour levels were achieved in LV + RA bypass. Cysteine and ribose reduced survival when added to the pump supported (LV + RA bypass) group. Cysteine/ribose improved survival over the no treatment group. O2 consumption increased significantly in the groups with best survival but remained unchanged from control or shock levels when cysteine/ribose were added. Unusually high levels of CPK, acid and alkaline phosphatase, and MDF occurred in both groups receiving cysteine/ribose, indicating significant organ damage correlating with poor survival. Lactate levels were less predictive. Heart tissue ATP levels were higher in groups with good survival. Liver ATP levels were lower in high survival groups. Lung ATP did not differ between groups. PMID- 8507975 TI - Does competing flow decrease the efficiency of internal mammary grafts? PMID- 8507976 TI - Typing recombinant inbred mouse strains for microsatellite markers. AB - In total, 41 different microsatellite variants have been typed in one or more of four different sets of recombinant inbred (RI) mouse strains. Microsatellite variants were selected that were located in chromosomal regions previously lacking markers. These markers extend the regions swept in these RI strains. PMID- 8507977 TI - 5' and 3' SINE-PCR allows genotyping of pig families without cloning and sequencing steps. AB - A microsatellite-containing clone, isolated from a pig Chromosome (Chr) 1 specific library was characterized by sequencing and computer analysis. The (CA)17 microsatellite motif was located at the 3' end of a short interspersed element (SINE) sequence at the position normally occupied by the oligo (A) stretch. Further computer analysis indicated that 12% of published pig SINE sequences contain dinucleotide repeat motifs adjacent to their 3' ends. By performing PCR with a single SINE primer in combination with a panel of arbitrarily selected unique primers, we have demonstrated that, as in human, polymorphisms can be detected and typed in pig family DNAs. A large number of SINE primer x unique primer combinations have been screened for the ability to detect polymorphisms in pig reference family DNAs. This approach does not require prior sequence information other than that of the pig SINE. We have also found polymorphisms at the 5' ends of pig SINE sequences by similar methods, but with a primer facing out to the 5' end of the SINE. PMID- 8507978 TI - Isolation of four HSP70 genes in the pig and localization on chromosomes 7 and 14. AB - For insight into the general organization of the swine leukocyte antigen (SLA) complex, the swine major histocompatibility complex (MHC), four sequences related to the heat-shock proteins HSP70 were characterized by screening of a pig genomic cosmid library with a swine cDNA HSP70 2.6-kb probe. This yielded three positive clones: HC2.2, HC3.2, and HC4.2. Restriction site maps revealed a large overlap of HC2.2 with HC3.2, whereas HC4.2 was independent. Southern blot hybridization with the 5' section, the central section, and the 3' section of the 2.6-kb probe and also with a swine 4.5-kb HSP70 genomic probe suggested the existence, within the overlapping clones, of three distinct HSP70 sequences encompassing a segment no longer than 22 kb. The HC4.2 clone, which hybridized with the same probes, displayed a single band of 7.3 kb, probably corresponding to one gene only. Fluorescent in situ hybridization on swine chromosome metaphases with the whole HC2.2 or HC4.2 cosmids allowed the assignment of HC2.2 to MHC region on Chromosome (Chr) 7 (Cen-p1.1), and of HC4.2 to Chr 14 (q2.4-2.5). Thus, as in humans, the swine MHC comprises three closely linked HSP70 loci. The presence of additional genes belonging to the same inducible HSP70 gene family can be expected from what is known in humans. The HSP70 gene found here on the pig Chr 14 may be one of these putative unidentified genes. PMID- 8507979 TI - A novel X-linked member of the human zinc finger protein gene family: isolation, mapping, and expression. AB - We report the partial characterization of a novel putative zinc finger gene of the Kruppel-type (ZNF81), isolated from an X Chromosome (Chr) specific library. The pattern of segregation in human-hamster somatic cell hybrids of sequences homologous to the ZNF81 finger domain has established that it resides within the Xp22.1-Xp11 region. ZNF81 represents yet another example, together with ZFX, ZNF41, and ZNF21, of members of the zinc finger gene family residing within the short arm of the human X Chr. Sequence analysis showed that ZNF81 may encode a polypeptide(s) containing tandem arrays of 12 canonical C2H2 zinc fingers of the Kruppel-type at the C-terminus. Northern analysis indicated that probes from the ZNF81 finger domain hybridize to polyadenylated transcripts present in several cell lines, a result that supports the hypothesis that it is an expressed, functional member of this multigene family. PMID- 8507980 TI - Microsatellites and associated repetitive elements in the sheep genome. AB - To determine the frequency and clustering of a variety of simple di- and trinucleotide repeats, an Artiodactyl short interspersed element (SINE), an ovine satellite repeat, and a human Alu 1 repeat were used to screen a random selection of cosmids containing inserts of ovine genomic DNA. In total, 197 individual cosmids were digested with EcoRI and the fragments separated on 0.7% agarose gels. Southern blots of these gels were then sequentially probed with (AC)7, (CT)9, and (CAC)6 oligonucleotides, and the repeats described above. The frequency at which (AC)n, (CT)n, and (CAC)n repeats were found in the cosmids indicated that they occurred at average intervals of 65 kb, 367 kb, and 213 kb respectively within the ovine genome. The Artiodactyl SINE was the most common, occurring at an average interval of 20 kb. No human Alu 1 sequences were detected. There was a significant positive association between the (AC)n and the Artiodactyl SINE. This association is quite strong as there was significant clustering of the two repeats both within cosmids and also within the EcoRI fragments of the digested genomic fragments. With the exception of the sheep satellite sequence, which occurs in tandem arrays, none of the other repeats showed significant clustering within the 41-kb (average size) cosmid inserts. The first 25 ovine microsatellites we characterized had an average polymorphic information content (PIC) of 0.65. The different microsatellite types, containing either perfect, imperfect, or compound repeats, had similar average PICs of 0.64, 0.65, and 0.66 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8507981 TI - Sequence analysis of mitochondrial chloramphenicol resistance mutations in Chinese hamster cells. AB - A series of mitochondrially inherited chloramphenicol-resistant (CAP-R) mutants were isolated in Chinese hamster cells. To determine whether the Chinese hamster CAP-R mutations were homologous to those isolated in mouse and human cell culture systems, we determined the nucleotide sequence of the region of the mitochondrial 16S rRNA gene spanning the peptidyl transferase-encoding region for eight CAP-R mutant lines in addition to the parental wild-type line. Three main conclusions are drawn from these studies. (1) Although the region of the gene encoding the peptidyl transferase domain is highly conserved relative to that of mice and rats, the contiguous sequences show less conservation. This sequence divergence not only includes the accumulation of single base pair replacements, but also the presence of small insertions or deletions. (2) For six of the CAP-R mutants, heteroplasmic single base pair changes were detected. These mapped to the same sites within the peptidyl transferase domain as the mutations found previously in mouse and human CAP-R mutants. (3) Two Chinese hamster CAP-R mutants, both with an unusual drug resistance phenotype, did not carry any mutations within the CAP R peptidyl transferase domain. However, both carried a heteroplasmic mutation at the position corresponding to nucleotide 2505 of the mouse 16S rRNA gene, a site predicted to map within a stem/loop structure attached to this key domain of the ribosome. This is the first evidence for mitochondrial CAP-R mutations that map outside the peptidyl transferase region. PMID- 8507982 TI - Molecular linkage of the morphogenetic mutation add and the zinc finger gene Gli3. PMID- 8507983 TI - Resolution of the staggerer (sg) mutation from the neural cell adhesion molecule locus (Ncam) on mouse chromosome 9. PMID- 8507984 TI - Murine serotonin transporter: sequence and localization to chromosome 11. PMID- 8507986 TI - A study of the stability of generalized wave gaits. AB - The wave gait has been observed in animal and insect walking and has been widely implemented in the control of walking machines. It has been proved that the wave gait possesses the optimum stability among all periodic gaits under the geometrical condition that R/P < or = 1, where R and P are respectively the stroke and pitch of a walking machine. Recently, based on numerical results, a generalized hexapodal wave gait was reported to be more stable than the wave gait for R/P > 1. In this paper, in order to understand more about the generalized wave gait, an analytical method is applied to study its stability in three categories of multilegged systems: quadrupeds, hexapods, and 2n-legged systems (n > or = 4). Two optimal generalized wave gaits are found for quadrupeds, and three optimal gaits are found for each of the other two categories. For all three categories, one of the optimal generalized wave gaits is the wave gait. The stability and geometrical conditions of these optimal gaits are derived and verified numerically. Furthermore, it is shown that the quadrupedal generalized wave gaits have the optimum stability among all periodic gaits with the stepping sequence 1-4-2-3. PMID- 8507985 TI - A novel tyrosine kinase-related sequence on mouse chromosome 5. PMID- 8507987 TI - Concentration-flux relations for a multicellular biological membrane with metabolism. AB - A mathematical model is described for the simultaneous diffusion and metabolism of a chemical penetrating a multicellular biological membrane such as skin. Metabolism is assumed to follow saturable Michaelis-Menten kinetics, which leads to nonlinear relationships between the applied concentration and the metabolic and diffusive fluxes through the membrane. Approximate concentration-flux relations are derived under limiting conditions, and a computational method is described for the general case. The major barrier to dermal penetration of very lipophilic molecules is thought to be the viable tissues (viable epidermis and some of the dermis) underlying the stratum corneum, and some molecules are known to be metabolized by enzymes within these tissues. It is proposed to use the model to describe penetration and metabolism of such lipophilic molecules within the viable tissues of the skin. PMID- 8507988 TI - Assessment of sexual mixing patterns. AB - The manner in which people with varying partner change rates choose their partners may have important implications for the future of the AIDS epidemic. A relatively rapid but small epidemic can be expected if sexual mixing patterns are highly assortative so that those with high partner change rates nearly always choose partners with similar rates. Direct estimation of sexual mixing is exceedingly difficult. On the other hand, information on the way people mix is implicitly contained in the epidemiology of other sexually transmitted diseases (STDs). If mixing is highly assortative, one might expect gonorrhea to be largely confined to a small subsection of the population who would frequently contract the disease repeatedly. In this paper a model of gonorrhea transmission in which partner change rates and preference are dealt with as continuous variables is used to extract information on mixing from data on an Australian heterosexual population. It was found that in this population mixing is not far from random with respect to partner change rates. PMID- 8507989 TI - Extension of a generalized state-vector model of radiation carcinogenesis to consideration of dose rate. AB - Mathematical models for radiation carcinogenesis typically employ transition rates that either are a function of the dose to specific cells or are purely empirical constructs unrelated to biophysical theory. These functions either ignore or do not explicitly model interactions between the fates of cells in a community. This paper extends a model of mitosis, cell transformation, promotion, and progression to cases in which interacting cellular communities are irradiated at specific dose rates. The model predicts that lower dose rates are less effective at producing cancer when irradiation is by X- or gamma rays but are generally more effective in instances of irradiation by alpha particles up to a dose rate in excess of 0.01 Gy/day. The resulting predictions are compared with existing experimental data. PMID- 8507990 TI - Mathematical modeling of T-cell proliferation. AB - A mathematical model of the T-lymphocyte proliferation process (in vivo and in vitro) is presented. This model takes into account cell-cycle progression and the regulation by lymphokines (lymphocyte activating factor interleukin 1 and T-cell growth factor interleukin 2). Using data on the generalized picture of the short term course of viral hepatitis B, the parameter estimation procedure is carried out. The possibility of immunocorrection (by means of injection of a pharmacologic dose of IL-2) during the immune response to viral hepatitis B with T-lymphocyte deficiency is shown. PMID- 8507991 TI - On the concentration profile of a growth inhibitory factor in multicell spheroids. AB - A mathematical model is presented for the production of a growth inhibitory factor (GIF) within a multicell spheroid. The main assumption of the model is that the GIF is produced by cells within the spheroid in some prescribed nonlinear, spatially dependent manner. Given that the diffusion of the GIF is known to take place over a much shorter time scale than that of spheroid growth, the steady-state profile of the GIF in various spheroids of differing radii is examined and theoretical results are compared with actual experimental data. PMID- 8507992 TI - [Adolescents and young adults with schizophrenic disorders and their management through the public health office]. PMID- 8507993 TI - [Reimbursement claims of severely handicapped patients in accordance with paragraph 53ff. SGBV--evaluation of social court verdicts]. AB - Sickness insurance bodies pay in case of necessity of nursing the seriously handicapped without having legally defined this term. The medical advisor of the sickness insurance (MDK) examines the necessity of nursing seriously handicapped persons. The article analyses existing social court judgements particularly concerning their consequences on the method of the medical adviser's assessment. The medical expert has to investigate those medical and social facts that are relevant for the administrative and judicial decisions and can appey the regulations of the major associations of the sickness insurances in case of necessity of nursing seriously handicapped persons. The adoption of not properly defined legal concepts from other sections of social legislation is discussed. PMID- 8507994 TI - [Prevention of sexually transmitted diseases or control of prostitutes and patients with venereal diseases? An exemplary, epicritical study in Bremen]. AB - Data derived from laboratory and activity statistics of the Venereal Disease" department of the Public Health Office in Bremen were analysed between 1961 and 1991. The traditional concept to fight venereal diseases" aimed at controlling persons "at risk" for syphilis, gonorrhoea, chancroid or lymphogranuloma. This "high-risk" approach of STD prevention stressed the compulsory, at least twice monthly screening of female prostitutes and neglected other population groups like clients of prostitutes and young people, who might have an elevated risk in acquiring STD. The spread of STD like chlamydia, HPV, herpes and even HIV in considerable parts of the general population underlines the need for developing a more effective STD prevention, based on scientific diagnosis and treatment. Intervention programmes in STD control must be performed in full partnership with the targeted population; this can require great effort and time. But STD control certainly cannot be achieved under the threat of punishment or proscription. PMID- 8507995 TI - [Multiple drug dependence]. AB - This study includes all inpatients of the years 1977-1988 treated for multiple drug abuse, in a psychiatric department of a general hospital in Berlin. The descriptive assessment of combined drug abuse in the last half year before admission for withdrawal treatment was the research object. 1176 persons with multiple drug abuse were admitted. The mean-value of age was 36.8 years, the duration of addictive behaviour 9.2 years and, they had 1.9 withdrawal treatments as inpatients before their admission here. On an average they took 2.91 substances simultaneously, predominantly alcohol and benzodiazepines. The third rank is occupied by combinations of analgesics, and the fourth one by heroin. Some preferred combinations with characteristic variables of their users are evaluated. PMID- 8507996 TI - [Ecology and causality--on the reliability of environmental medicine knowledge]. AB - In principle, environmental medicine has two responsibilities. On the one hand this special field is required to provide a practicable and enlightening medicine for people seeking help. On the other hand environmental medicine as an ecological medicine" is required to analyse the truth content in science and the reliability of scientific knowledge with regard to environmental processes. For not only direct-acting toxicities of environmental chemicals but also the imbalance in ecological systems possess pathogenic potencies. Do these ecological processes in systems actually have the demanded obvious causality? PMID- 8507997 TI - [Polycyclic aromatic hydrocarbons on play grounds--presentation of current status, toxicologic viewpoints and attempt at risk assessment for benzo(a)pyrene]. AB - Polycyclic aromatic hydrocarbons (PAH) have become an ubiquitous upper soil component in consequence of industrialisation involving a multitude of combustion processes. Meaningful contaminations can be found on child playgrounds, for example. These may enter into the organism of small children playing there, as children are capable of unintentionally swallowing minute quantities of foreign matter - be that as it may, we cannot exclude such a possibility. Suitable rules are mandatory in particular to prevent such occurrences in an area that is susceptible to them, as preventive health care should always be the order of the day. In the following article we report on the present scientific-toxicological state of the art, on update data on environmental pollution and reasons for a quantitative risk assessment for different paths of pollution. PMID- 8507998 TI - [Infusion technique as a significant aspect of public health monitoring of hospitals--a case report]. AB - An outbreak of septicaemia caused by Acinetobacter involved eight patients of an ICU within a period of 6 days. All patients were treated with heparin infusions. We isolated Acinetobacter from the blood of all these patients and from a mixture of heparin and isotonic saline solution. As underlying causal event a combination of risk factors and mistakes is suggested. These may include the multiple reuse of infusion bottles by different users, the reuse of perfusor injectors, and underscores the necessity of strict hygienic precautions. This event points to a disseminated risk factor that should be considered within the frame of control systems for hospitals. PMID- 8507999 TI - [Position of the Commission of Presiding Physicians on the current status of medical service in health insurance]. PMID- 8508000 TI - [Structures and methodologic issues of a central department of inpatient management]. PMID- 8508001 TI - [Deafness in childhood]. PMID- 8508002 TI - Moving into power: innovative nursing. PMID- 8508003 TI - Increasing incidence and mortality rates of soft tissue sarcoma in Western countries? PMID- 8508004 TI - Twenty-five years of renal transplantation from a single center: a risk factor analysis for short- and long-term outcomes. AB - Between 1966 and 1991 a total of 1000 renal transplants were performed in Erlangen-Nuremberg. Patients were operated upon in Erlangen and transferred immediately 25 km to Nuremberg for their postoperative and immunosuppressive care. Despite these considerable logistical obstacles, the 10-year graft survival rate in 785 consecutive transplants performed between 1980 and 1990 was 44%, while patient survival was 84%. Mismatch at the HLA-DR locus, preformed antibodies, multiple transplants, and kidneys from donors aged 10 years or younger or over 60 years were risk factors for decreased graft survival. An immunosuppressive regimen of cyclosporine and methylprednisolone resulted in better graft survival than did azathioprine and methylprednisolone, or reduced dose cyclosporine, azathioprine, and methylprednisolone. The cyclosporine and methylprednisolone regimen had a better patient survival than azathioprine and methylprednisolone. A hazard analysis demonstrated a particular risk of late rejection between the 70th and 90th months, after transplantation. Our data indicate that favorable transplant results can be obtained despite major logistical disadvantages. Very close cooperation between referring centers, transplant surgeons, and nephrologists is indispensable for success. PMID- 8508005 TI - Clinical features of type III hyperlipoproteinemia: analysis of 64 patients. AB - The clinical and biochemical characteristics of type III hyperlipoproteinemia are described in 64 patients (35 males and 29 females). Homozygosity for apolipoprotein E2, the presence of an abnormally cholesterol-rich very low density lipoprotein fraction (beta-VLDL) and an elevated ratio of very low density lipoprotein cholesterol to plasma triglycerides (> 0.3; normal ratio about 0.2) were the basis for the diagnosis. Mean serum cholesterol and triglyceride concentrations at the first visit in the clinic were 426 +/- 221 and 719 +/- 996 mg/dl, respectively. The mean age at diagnosis of the disorder was 49 years in males and 53 years in females. There was a high prevalence of obesity (72%), xanthomas (42%), and atherosclerosis (39%), especially peripheral vascular disease (31%). Early and correct diagnosis of this familial lipoprotein disorder seems necessary because of the prompt and beneficial response to therapeutic interventions. PMID- 8508006 TI - Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L thyroxine treatment. AB - Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of L-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month L-thyroxine course (0.1-0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ) = 89.1 +/- 2.9; P = 0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P = 0.03), anxiety (P = 0.05), somatic complaints (P = 0.0005), and depressive features (P = 0.002) scales; the total score was also significantly higher (42.0 +/- 3.8; P = 0.005). After L-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9 +/- 4.0; P = 0.002 (treated versus untreated)]; somatic complaints (P = 0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P = 0.04) significantly decreased with respect to untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508007 TI - Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion. AB - It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 +/- 0.61 to 5.77 +/- 0.78 mmol/l and from 5.61 +/- 2.05 to 7.55 +/- 3.05 mmol/l, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508008 TI - Insulin enhances angiotensin II induced DNA synthesis in vascular smooth muscle cells of the rat. AB - Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 x 10(-10) 1.7 x 10(-6) M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin II induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin II. In conclusion, insulin is able to enhance angiotensin II induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells. PMID- 8508009 TI - Effects of garlic coated tablets in peripheral arterial occlusive disease. AB - For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication. PMID- 8508010 TI - Gottron's acrogeria and sarcoidosis. AB - The case of a 37-year-old male suffering from Gottron's acrogeria and cutaneous sarcoidosis is presented together with a thorough review of the literature. So far about 40 cases of Gottron's acrogeria have been described. An association of sarcoidosis and acrogeria has not been observed to date. PMID- 8508012 TI - Immune thrombocytopenia associated with hemorrhagic diathesis due to ibuprofen administration. AB - Acute thrombocytopenic purpura temporally related to the oral administration of ibuprofen developed in a patient with ankylosing spondylitis. Clinical manifestations, with sudden onset occurring within 12 h of drug ingestion and rapid increase of platelet counts following discontinuation of the drug, were characteristic of an antibody-mediated immune pathomechanism. Immunological studies demonstrated IgM and IgG antibodies in the patient's serum that were capable of binding to allogenic platelets in the presence of a metabolite preparation. This finding suggested that an ibuprofen metabolite, rather then the drug itself, was the antigenic agent responsible for the immune reaction. Despite its widespread therapeutic use, ibuprofen has not been described previously as causing immune-mediated thrombocytopenia. PMID- 8508011 TI - Ovarian sex steroids and atherosclerosis. AB - Estrogens have been found to protect against atherosclerosis in a variety of animal models, and these antiatherogenic properties have been confirmed by epidemiological and clinical studies in women as well. Since the estrogen-induced changes of plasma lipid and lipoprotein levels do not fully account for the prevention of atherosclerosis, additional effects must be assumed. Experimental studies suggest various direct vascular actions. Estrogens enhance the endothelial degradation of low-density lipoprotein cholesterol, and preliminary data indicate antioxidative actions on low-density lipoprotein particles in macrophages. They suppress intimal proliferation and extracellular matrix production in the arterial wall and induce marked vasodilatation in systemic and coronary arteries. Adverse effects on hemostatic factors described with high doses and synthetic compounds are not evident during hormonal replacement in postmenopausal women, in whom an estradiol-induced inhibition of platelet aggregation may even have beneficial clinical effects. The role of progesterone and other progestogens in the progression of atherosclerosis is controversial. Despite a partial antagonism to estrogen-induced changes of plasma lipids, their addition to estrogens does not alter the anti-atherosclerotic properties, at least in animal experiments. The direct vascular actions of progestogens-although not as well documented-seem to be less pronounced than those of estrogens. The experimental data indicate that direct vascular effects play an important role in the antiatherogenic properties of ovarian sex steroids. However, the underlying cellular and molecular mechanisms remain largely unknown. PMID- 8508013 TI - Study of serum procollagen type III peptide in patients with hepatic cirrhosis from a clinical point of view. AB - N-terminal procollagen-III peptide (P-III-P) has been considered a marker of fibrogenesis and inflammatory activity of the liver. We measured the P-III-P serum levels in 83 cirrhotic patients fully characterized from a clinical and laboratory point of view. Cirrhotic patients had significantly higher P-III-P serum levels than controls (P < 0.0001). Of the cirrhotic patients 73.5% had increased P-III-P. A significant negative correlation was found between P-III-P and transaminases, and patients with normal values of alanine amino-transferase had higher P-III-P serum levels than those with increased values (P = 0.03). On the other hand, no significant association was found with portal hypertension, Child classes, or alcoholic liver disease. No one independent factor appears to be responsible for the increase in P-III-P. The measurement of serum P-III-P is of little if any use in the evaluation of cirrhotic patients. PMID- 8508015 TI - Principles of PREP. PMID- 8508014 TI - Skill mix is not grade mix. PMID- 8508016 TI - Prescribed hydration in palliative care. AB - Whether or not to support artificial hydration in palliative care is a difficult choice for all the health care team. It is vital that the final decision is based on current knowledge so that the patient can die in comfort and with dignity. PMID- 8508017 TI - Role of hydrocolloids in wound management. AB - This article describes the actions of hydrocolloid dressings and the type of wounds for which they are most suitable. The range of hydrocolloid products is reviewed along with their individual advantages and disadvantages. PMID- 8508018 TI - Child sexual abuse. 3: Treatment and recidivism in paedophiles. AB - Although various courses of treatment for paedophilia have been tried, there is little evidence of their effectiveness. Important factors that mitigate against success are the inability of paedophiles to see their sexual activity as warranting treatment and their reluctance to change their behaviour. PMID- 8508019 TI - Heartwatch: screening employees for heart disease risk factors. AB - Heartwatch is a project set up to screen workers for risk factors of coronary artery disease, provide practical advice and decrease risk factors in the workplace. It combines clinical measurements using portable equipment with results from a questionnaire. The information is processed by a computer to generate a personalized report. PMID- 8508020 TI - Pathways for PREP: a consumer-orientated model. PMID- 8508022 TI - A&E nurses: from Cinderella to Queen Bee. PMID- 8508021 TI - Implications of the community education and practice project. AB - A key feature of the Community Education and Practice (CEP) Project (UKCC, 1991) was the recognition that nurses should be appropriately trained if they choose to work in the community. The University of Central England (UCE) in Birmingham has developed a Diploma in Professional Studies in Nursing (Community Health Studies) course in order to fulfil this goal. PMID- 8508024 TI - Lifting techniques for nurse-aiders. AB - When giving first aid, nurse-aiders must assess the working environment and make it safe or either remove the patient from it. If movement is necessary, nurses must keep in mind their own bodily capability. PMID- 8508023 TI - Children and consent to medical treatment. AB - In English law, a person aged 16 or over may give valid consent to medical treatment. Under the age of 16, a person who is of sufficient understanding and intelligence may also give valid consent. The right to withhold consent is not comparable. PMID- 8508025 TI - Oxford to Australia: symbiotic nursing relationship. AB - With the implementation of postregistration education and practice (UKCC, 1990) nurses are now looking forward to developing themselves personally and professionally. In order to facilitate this the John Radcliffe Hospital, Oxford, has set up observational visits to hospitals in Australia. This article describes one of these visits. PMID- 8508026 TI - Tissue-specific restriction of skeletal muscle troponin C gene expression. AB - Expression of the skeletal muscle troponin C (TnC) gene is confined to fast twitch skeletal muscle fibers (Gahlmann et al., 1988) and appears to be subject to an unexpected form of regulation. Unlike enhancers of other muscle genes, the TnC enhancer and basal promoter are muscle cell-specific only when linked to each other. We identified a strong classical enhancer element within the 5'-flanking sequence of this gene at -1.5 kb and a basal promoter near the transcription start site. Both elements are required for the transcriptional activity of TnC test constructs in myogenic cells. When the TnC enhancer was linked to the SV40 early basal promoter, or the TnC basal promoter was linked to the SV40 enhancer, each supported expression in non-muscle cells. Nuclear factors from both muscle and non-muscle cells bind to one CTF/NF1 binding site and to two functionally related MEF2-like A/T-rich binding sites in the enhancer element. It is currently unknown whether modifications of these nuclear factors, differences in their concentrations, or their interaction with additional factors restrict human fast twitch TnC expression to skeletal muscle cells. However, it appears that the human fast-twitch skeletal troponin C gene is restricted in non-muscle cells in a distinctive way requiring communication between its enhancer and basal promoter. PMID- 8508027 TI - In situ analysis of C. elegans vitellogenin fusion gene expression in integrated transgenic strains: effect of promoter mutations on RNA localization. AB - Expression of the Caenorhabditis elegans vitellogenin (vit) genes is initiated at the larva-to-adult molt in all of the 30 to 34 nuclei of the hermaphrodite intestine. A series of strains in which DNA carrying a vit fusion gene was integrated at low copy number was analyzed by in situ hybridization to determine whether the transgene showed the same tissue-specific expression. Strains with only 247 bp of 5'-flanking DNA accumulated the mRNA product of the introduced vitellogenin gene only in the adult hermaphrodite intestine, and uniformly in all of the intestinal cells. When similar strains carrying vit fusion genes with promoter modifications were tested, no loss of tissue specificity was observed. Surprisingly, however, strains with modified promoters that resulted in reduced levels of expression displayed a novel pattern of transgene RNA localization within their intestines. Strains with severe promoter defects accumulated the transgene mRNA in the central part of the intestine but lacked the mRNA at both ends. Those with less severe promoter mutations lacked the transgene mRNA only in the most anterior intestinal cells. We hypothesize that genes with altered promoters require higher activator concentrations to express the reporter gene, thus revealing an inherent asymmetry in activator levels, lowest in the anterior cells and highest in the central cells of the intestine. PMID- 8508028 TI - Distinct negative regulation of the human embryonic globin genes zeta and epsilon. AB - The human embryonic globin genes zeta and epsilon are expressed when erythropoiesis is initiated at about the third week of development but are subsequently repressed as expression of the fetal globins, alpha and gamma, begins. We have examined the promoter region of the human zeta-globin and epsilon globin genes in order to identify regulatory sequences that may be involved in this process. Stable transfection of the human erythroid cell line K562 with either a truncated form of the zeta-globin gene, containing 112 base pairs (bp) of 5'-flanking sequences, or a larger zeta-globin construct, containing several hundred bp of 5'-flanking sequence, revealed that the zeta-globin gene is subject to negative regulation by its 5'-flanking region. We have defined the sequences responsible for this negative regulation to a 22 bp region immediately upstream of the proximal promoter sequence of the zeta-globin gene. A 22 bp oligonucleotide including this negative element was found to inhibit both the zeta-globin and HSV TK promoters. We have also analyzed the promoter of the human epsilon-globin gene, since it is coordinately expressed with zeta-globin. We show that it is likewise subject to negative regulation, though in this case from a distal silencer element. Gel retardation and methylation interference assays have provided evidence of a factor which binds specifically to the epsilon-globin silencer. However, no obvious sequence homology exists between the zeta and epsilon negative elements, and at least some of the factors that recognize these elements are distinct. We postulate that the negative transcriptional control elements in the human embryonic globin gene promoters contribute to the observed reduction in zeta- and epsilon-globin gene expression that occurs during development. PMID- 8508029 TI - Yeast RNA polymerase II subunit RPB11 is related to a subunit shared by RNA polymerase I and III. AB - The characterization of RNA polymerase subunit genes has revealed that some subunits are shared by the three nuclear enzymes, some are homologous, and some are unique to RNA polymerases I, II, or III. We report here the isolation and characterization of the yeast RNA polymerase II subunit RPB11, which is encoded by a single copy RPB11 gene located directly upstream of the topoisomerase I gene, TOPI, on chromosome XV. The sequence of the gene predicts an RPB11 subunit of 120 amino acids (13,600 daltons), only two amino acids shorter than the RPB9 polypeptide, that co-migrates with RPB11 under most SDS-PAGE conditions, RPB11 was found to be an essential gene that encodes a protein closely related to an essential subunit shared by RNA polymerases I and III, AC19. RPB11 contains a 19 amino acid segment found in three other yeast RNA polymerase subunits and the bacterial RNA polymerase subunit alpha. Some mutations that affect RNA polymerase assembly map within this segment, suggesting that this region may play a role in subunit interactions. As the isolation of RPB11 completes the isolation of known yeast RNA polymerase II subunit genes, we briefly summarize the salient features of these twelve genes and the polypeptides that they encode. PMID- 8508030 TI - Selection between a natural and a cryptic 5' splice site: a kinetic study of the effect of upstream exon sequences. AB - To study the mechanism of selection of 5' splice sites, we first analyzed the in vitro time course of appearance of intermediates and products of splicing at a natural and at a cryptic 5' splice site. Our model system was a transcript derived from the early transcription unit 3 of adenovirus-2 harboring a cryptic 5' splice site Dcr1, 74 nucleotides downstream of the natural site D1. When studied in isolation, the two sites have different kinetics of splicing, Dcr1 being spliced markedly more slowly than D1. The upstream exon, shown elsewhere to have a positive effect on the selection of D1, has no influence on these kinetics; thus, it does not affect selection by modifying the kinetics of splicing. Nevertheless, this exon is of crucial importance for the exclusive selection of D1. We demonstrate that the cryptic site is recognized in all cases, but that exons harboring a potential stem-loop structure (HP1) prevent Dcr1 usage. The data suggest that the upstream exon sequences play the role of a cis acting selector for the natural 5' splice site. The intrinsically rapid and efficient kinetics of splicing at the natural site and the selector function of the exon sequence may result in the exclusive use of the D1 site in the natural context. PMID- 8508032 TI - Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging. AB - BRAINBLAST, a program that uses voxel processing, was developed in order to produce high-fidelity three-dimensional reconstructions of the brain. Four steps were used to produce images: washing away cerebrospinal fluid (via histogramming), dissecting away the blood vessels (via a connectivity heuristic), highlighting the sulci and gyri (via a lighting model), and resampling the interior contents of the brain. After reconstruction, the images can be resampled, rotated, written on, measured, or redissected. The technique has a variety of applications: study of individual variation in sulcal and gyral patterns, evaluation of structure/function relationships, measurement of volumes or subregions using anatomically defined landmarks, and teaching of neuroanatomy. PMID- 8508031 TI - p53 domains: suppression, transformation, and transactivation. AB - We investigated the suppression, transformation, and transactivation functions of isolated segments of wild-type murine p53. Intact p53, but no segment of p53, inhibited cellular transformation by the activated ras and adenovirus E1A proteins. We conclude that most of p53 is needed for suppression of cellular proliferation. Nevertheless, the transactivating domain of herpesvirus protein VP16 was able to substitute for the N-terminal transactivating domain of p53 in cellular suppression. Thus, unless the interchanged p53 and VP16 acidic segments share additional functions, transactivation is required for suppression by p53. Interestingly, we found that all p53 segments containing amino acids 320-360 enhanced transformation by ras and E1A. This region has been associated with the oligomerization of p53 (Milner et al., 1991; Sturzbecher et al., 1992). Furthermore, no p53 segment lacking amino acids 320-360 transformed cells. Amino acids 320-360, therefore, may account for the major transforming activity of p53. Intact p53 and chimeric VP16-p53 transactivated the CAT gene under control of a p53-specific promoter, while transforming segments of p53 interfered with transactivation by wild-type p53. Our findings argue that transactivation by p53 is required for cellular suppression and that any nontransactivating p53 that retains the capacity to oligomerize with wild-type p53 would have transformation potential. PMID- 8508033 TI - Neurobiology and sexual orientation: current relationships. AB - Despite great progress in the neurosciences, our understanding of the determinants of sexual orientation is incomplete. The authors review for the clinician/neuropsychiatrist studies pertaining to the formation of sexual orientation in the following areas: hormone effects on sexual behavior (animal and human); the complicated relationship between gender identity, gender role, and sexual orientation in humans; cross-cultural studies of homosexuality; behavioral observations in pseudohermaphrodites and offspring of mothers treated with hormones during pregnancy; brain studies of homosexual and heterosexual individuals; and genetic studies. The authors conclude that human sexual orientation is complex and diversely experienced and that a biopsychosocial model best fits the current state of knowledge in the field. PMID- 8508034 TI - Delirium. PMID- 8508035 TI - Mild neurocognitive disorder: needed addition to the nosology of cognitive impairment (organic mental) disorders. PMID- 8508036 TI - Neurological status of Vietnam veterans with chronic posttraumatic stress disorder. AB - This study investigated neurological status in 27 medication-free outpatient Vietnam veterans meeting DSM-III-R criteria for posttraumatic stress disorder (PTSD) and 15 non-PTSD combat control subjects, all without alcohol or drug dependence or abuse during the past year. Subjects underwent neurological examination, neuropsychological testing, and sleep-deprived EEG. PTSD subjects showed significantly more neurological soft signs than non-PTSD subjects. Neither substance dependence/abuse nor the more frequent history of developmental problems in PTSD subjects accounted for this difference. There were no significant EEG or neuropsychological testing group differences; however, there were significant correlations between several neuropsychological test scores and total neurological soft signs. PMID- 8508037 TI - Catastrophic reaction after cerebrovascular lesions: frequency, correlates, and validation of a scale. AB - The frequency and correlates of the catastrophic reaction (CR) were examined in 52 consecutive patients with an acute stroke lesion. A new scale proved reliable for measuring the severity of CR. The CR was significantly associated with depression, a personal and family history of psychiatric disorder, and subcortical lesions, which were mostly located in the basal ganglia. Patients with and without a CR, when matched for the presence and type of depression, differed only in that CR patients had significantly more anterior lesions and a significantly higher frequency of subcortical damage. Results demonstrate that the CR is significantly associated with poststroke depression and may be a specific manifestation of certain types of poststroke depression. PMID- 8508038 TI - Adult familial dyslexia: a retrospective developmental and psychosocial profile. AB - This study investigated the developmental, demographic, educational, and psychosocial outcome of 36 adults with third-generation familial dyslexia. Control subjects were 44 unaffected age-matched family members. Compared with control subjects, those with familial dyslexia 1) had similar incidences of perinatal complications, left-handedness, and right-left confusion but reported more early speech/language problems; 2) performed worse in reading and spelling but had similar educational achievement; 3) were more likely to report depression/anxiety symptoms and to have attention-deficit disorder with hyperactivity; and 4) were similar in medical history, marital stability, and mean income. Data suggest that, despite continued isolated reading deficits, carefully selected subjects with adult familial dyslexia do not show the previously described downward course of the learning-disabled population. PMID- 8508039 TI - A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression. AB - Chronic fatigue syndrome (CFS), a controversial clinical entity characterized by severe fatigue and constitutional symptoms, has been associated with a variety of psychiatric disorders. To further understand the psychiatric profile of CFS, the authors compared patients with CFS, multiple sclerosis (MS), and major depression by using diagnostic interviews and self-report measures of Axis I disorders and personality disorders. CFS patients differed from patients with major depression, with significantly less depression and fewer personality disorders. Compared with MS patients, CFS patients did not differ with regard to personality disorders. However, they did have significantly more frequent current depression than MS patients, particularly following onset of their illness. PMID- 8508040 TI - Clozapine use in diffuse Lewy body disease. AB - Diffuse Lewy body disease, a severely disabling neuropsychiatric disease, presents with progressive dementia, psychotic symptoms, depression, and parkinsonian symptoms. The authors report a case illustrating that clozapine, a novel neuroleptic drug, has special efficacy in treating psychotic symptoms in these patients. PMID- 8508041 TI - Association of anticholinergic activity of prescribed medications with postoperative delirium. AB - In a prior study, delirium and plasma anticholinergic drug levels were significantly correlated in 9 of 25 surgical intensive care patients. The present study, using cumulative anticholinergic effects of parent compounds of these patients' medications, found that delirious patients' medication combinations had significantly higher cumulative anticholinergic effects than those of nondelirious patients. PMID- 8508042 TI - Impairment in driving and psychiatric illness. PMID- 8508043 TI - Broca's aphasias and area 44. PMID- 8508044 TI - Neuroimaging findings in a case of progressive multifocal leukoencephalopathy. PMID- 8508045 TI - DSM-IV: "cognitive disorders". PMID- 8508046 TI - Proposed DSM-IV criteria for "postconcussive disorder". PMID- 8508047 TI - Holzer's method and GFAP immunocytochemistry. PMID- 8508048 TI - Immunoglobulin genes in autoimmunity. AB - The contribution of V germline genes and somatic mutation as well as the mechanism governing expression of the various V family genes in response to self antigens are still unknown. Thus, we are still far from understanding the contribution and role of the B cell repertoire in human autoimmunity. Much of our current data on autoantibody gene repertoire are derived from laboratory generated hybridomas or animal model of autoimmune diseases. These may not reflect the human situation. In contrast, very few human autoantibodies with defined specificities have been structurally and genetically analyzed. In the future, meaningful data, perhaps from direct cloning and sequencing of autoantibodies derived from patients with autoimmune diseases, will be necessary to resolve issues in autoantibody repertoire usage. In this article, the prominent features of the human Ig repertoire, the usage of germline genes in autoantibodies, identifications of somatic mutations among autoantibodies and current data supporting either restricted or nonrestricted Ig gene usage and idiotypic expression among autoantibodies in several well-studied autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis are discussed. PMID- 8508049 TI - HLA and Singaporean Chinese myasthenia gravis. AB - Chinese Singaporean myasthenia gravis (MG) patients are associated with three HLA haplotypes: Cw1 B46 DRB1*0901 DQB1*0303 DQA1*03, DRB1*14 DRB3*0202 DQB1*0503 DQA1*0101 and DRB1*1202 DRB3*0301 DQB1*0301 DQA1*0601. The B46 haplotype was associated with the total group of MG patients but in particular with those with younger onset, low antiacetylcholine receptor (anti-AchR) titres, with only ocular lesions and with normal thymuses. The DRB1*14 haplotype was associated with thymic hyperplasia, younger onset patients, with high anti-AchR titres and with generalised MG. The DRB1*1202 haplotype was associated with thymoma, older onset patients, ocular lesions, and mid to high anti-AchR titres. PMID- 8508050 TI - Thymulin modulates cytokine release by peripheral blood mononuclear cells: a comparison between healthy volunteers and patients with systemic lupus erythematosus. AB - Thymulin is a nonapeptide hormone isolated from the thymus gland. It has immunomodulatory effects which have not yet been well defined. Its major actions have been shown to be on T-cells and their immature precursors. In this study, thymulin was tested in vitro for its effect on the release of IL-1 alpha, IL-2, IL-6 and TNF alpha from peripheral blood mononuclear cells (PBMC) obtained from normal volunteers and patients with active systemic lupus erythematosus (SLE). In our experiments, PBMC (stimulated with LPS or PHA) were cultured for 24 h in the presence of 1,100 or 1,000 ng/ml of thymulin. Supernatants were subsequently assayed for cytokine activities using commercially available ELISA (IL-2, IL-6 and TNF alpha) and RIA (IL-1 alpha) kits. Thymulin (1 ng/ml) resulted in a significant (p < 0.01) increase in IL-1 alpha in the volunteers and a significant (p < 0.05) inhibition of this cytokine at all dose levels tested in SLE patients, whose basal levels of IL-1 alpha were significantly (p < 0.05) higher. Thymulin significantly (p < 0.05) inhibited IL-2 only in SLE patients at 1,000 ng/ml. At all dose levels tested, thymulin significantly (p < 0.01) inhibited IL-6 in volunteers, and, only at 1,000 ng/ml, it significantly (p < 0.05) inhibited it in patients with SLE. At the 1,000 ng/ml dose level, TNF alpha was significantly (p < 0.05) inhibited in both volunteers and SLE patients, whose basal levels of this cytokine were significantly (p < 0.05) higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508052 TI - Determination of three disulfide bonds in a major house dust mite allergen, Der f II. AB - Der f II is a major mite allergen consisting of 129 amino acid residues. Der f II contains six cysteine residues, suggesting the existence of three disulfide bonds which would stabilize this small protein. As the first step in revealing the relationship between the structure and the allergenic property of Der f II, the formation of disulfide bonds was examined. Der f II purified from Dermatophagoides farinae was treated with lysyl-endopeptidase or proline-specific endopeptidase, and the peptide fragments thus generated were separated by reverse phase high performance liquid chromatography. Determination of the amino acid sequence of each peptide collected in this way proved the existence of three disulfide bonds between Cys8 and Cys119, Cys21 and Cys27, and Cys73 and Cys78. PMID- 8508051 TI - Ultrastructural localization of prostaglandin endoperoxide synthase (cyclooxygenase) to isolated, purified fractions of guinea pig peritoneal macrophage and line 10 hepatocarcinoma cell lipid bodies. AB - Subcellular fractions of purified cytoplasmic, nonmembrane-bound lipid bodies were prepared from [3H]-arachidonic acid-labeled guinea pig peritoneal macrophages and line 10 hepatocarcinoma cells. These fractions, which contained [3H]-arachidonyl lipids, were shown to be devoid of contaminating cellular membranes by electron microscopy, and to contain prostaglandin endoperoxide (PGH) synthase by postembedding immunogold electron microscopy. These findings support a proposed role for these lipid-rich organelles in the generation of eicosanoids by oxidative metabolism of arachidonate in the cyclooxygenase pathway of inflammatory and neoplastic cells. PMID- 8508053 TI - Control of IgE responses. 4. Isotype-specific suppression of peak BPO-specific IgE antibody-forming cell responses and of BPO-specific IgE in serum by muramyldipeptide or murabutide after administration to mice by gavage. AB - Muramyldipeptide (MDP) and murabutide (MB) suppressed hapten-specific IgE antibody-forming cell (AFC) responses in vivo. IgE responses were induced in BALB/c mice by intraperitoneal injection with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) (10 micrograms) in aluminum hydroxide gel (Alum) on days 0, 21 and 42. On day 44, mice were fed (gavage) or injected subcutaneously with varying concentrations of MDP or MB (0.1-500 mg/kg). The mice were killed on days 45-70, and the numbers of BPO-specific IgM, IgG1, IgE, and IgA AFC in various lymphoid organs were determined in an enzyme-linked immunosorbent spot (ELISPOT) assay. In addition, levels of BPO-specific IgE in serum were determined by ELISA. Data are expressed as AFC/10(7) cells or as micrograms/ml. Feeding with MDP or MB on day 44 suppressed BPO-specific IgE AFC responses and serum levels of BPO specific IgE within 48 h (day 46) (65-100% and approximately 50% decrease, respectively). With both molecules, the suppression was IgE isotype-specific, dose-dependent and transient. The suppression was also route-specific since it was obtained only when MDP or MB were given by gavage, and not when injected subcutaneously. These results show that peak antigen-specific IgE responses can be downregulated in vivo, in isotype-specific fashion, by a clearly defined class of molecules, MDP and MB, one of which, MB, is a candidate for clinical studies in man. The mechanism of suppression probably involves the modulation of gut associated lymphoid tissue and mucosal immunity. The clinical implications are that pharmacologic agents of this type may be suitable for use in the therapeutic or prophylactic downregulation of IgE and, hence, in the therapy of IgE-mediated diseases in man such as allergic rhinitis, asthma, and other atopic diseases. PMID- 8508054 TI - Incidence of latex allergy in atopic children and hospital workers in Japan. AB - The incidence of latex-induced allergy has been reported to be increasing in Europe and the US but not in Japan. We thus measured latex-specific IgE antibodies and latex-specific IgG antibodies in sera from 196 atopic children with low serum IgE levels (under 1,000 U/ml; group 1), 108 atopic children with high serum IgE levels (over 1,000 U/ml; group 2) and 601 hospital employees (group 3). Atopic children were diagnosed as having asthma, atopic dermatitis and/or food intolerance. One out of group 1 (0.5%) and 11 out of group 2 (10.2%) were found to have latex-specific IgE by radioallergosorbent assay (RAST), and 7 were further found to be positive for latex antigen by skin test. Fifty-five percent of group 1, 65% of group 2 and 9.7% of group 3 were found to have latex specific IgG over 100 units/ml by enzyme linked immunosorbent assay (ELISA). Prior to our diagnosis most of the children and employees did not realize they were allergic to latex. These data suggest that caution should be taken regarding latex allergy when atopic children have to be operated upon as atopic children tend to be sensitized to the latex antigen after even minimal contact with latex products. PMID- 8508055 TI - Changes in phenotypically distinct phagocyte subpopulations during nonspecific modulation of contact sensitization. AB - Environmental influences are increasingly recognized as nonspecific modulators triggering and aggravating allergic diseases. To obtain better insight into the pathomechanisms of these nonantigen-specific phenomena, we studied the augmenting and inhibitory effects of croton oil and glucocorticosteroid (GC) on the induction of murine allergic contact dermatitis. Application of the irritant croton oil simultaneously with the sensitization dose of the contact allergen oxazolone strongly amplified the inflammatory reaction (measured as ear swelling) during the effector phase. Immunohistologically, this effect correlated with an increased percentage of MRP8- and MRP14-positive phagocytes in the infiltrate of the early inflammatory reaction 8 h after sensitization with oxazolone plus croton oil as compared to oxazolone alone (62 vs. 27%; p < 0.05). Intravenously administered GC was used as an inhibitor of contact sensitization. The suppressive effect of GC on sensitization was dependent on the time of its application: suppression of the inflammatory reaction during the effector phase was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization. Correspondingly, the percentage of BM8-positive macrophages in the infiltrate of the early inflammatory reaction 8 h after sensitization was differentially decreased depending on the time of GC application: suppression of the percentage of BM8-positive macrophages was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization (17 vs. 25%; base value without GC 35%; p < 0.05). Furthermore, the percentage of BM8-positive macrophages in the inflammatory infiltrate of the effector phase was increased when sensitization had been enhanced by concomitant irritant contact dermatitis (47 vs. 59%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508056 TI - Allergic reactivity of children of different socioeconomic levels in tropical populations. AB - Widely variable prevalences of allergic diseases have been reported in tropical populations, and this has been suggested to be due to effects of the nonspecific polyclonal stimulation of IgE synthesis caused by the helminthic infections that are endemic in these areas. Since 1980, we have been evaluating the allergic reactivity of different socioeconomic sectors of the population of tropical Venezuela (lat. 2-12 degrees N), and in the present study analyze the overall results obtained in the laboratory evaluation of children (5-15 years of age) belonging to these groups. Children of medium-high socioeconomic level (M-HSEL), who experience occasional helminthic infections, have moderately high total serum IgE levels, and have elevated skin test positivities and specific IgE levels against environmental allergens. Persons of low socioeconomic level, in the urban, and particularly rural situation experience frequent helminthic infection, and have highly elevated total serum IgE levels. In contrast to the M-HSEL, the majority of these children have detectable specific IgE antibody against a variety of inhalant allergens, but relatively few have high levels, and their skin test positivity is also low. In these frequently parasitized persons, evidence of saturation of mast cell Fc epsilon receptors was found by tests of passive sensitization. We propose, therefore, that helminthic parasites have a biphasic effect on allergic reactivity; occasional infections are stimulatory, via their nonspecific potentiation of IgE synthesis against environmental allergens, and frequent infections are suppressive due to the widely polyclonal stimulation that they cause, resulting in both diminished specific antibody production against any given allergen and mast cell Fc epsilon receptor saturation. PMID- 8508057 TI - Late asthmatic response causes peripheral airway hyperresponsiveness in dogs treated with metopirone. AB - To determine if late asthmatic response (LAR) is associated with hyperresponsiveness of airway smooth muscle itself, we performed antigen challenge in dogs treated with Metopirone. We studied the contractile response to acetylcholine (ACh) in isolated bronchial and bronchiolar segments 8 h after either saline inhalation (the control group) or antigen challenge in dogs demonstrating immediate asthmatic response (IAR) alone and in dogs demonstrating both IAR and LAR. Airway responses to Ascaris suum antigen were assessed by changes in respiratory resistance measured with the forced oscillation technique at 3 Hz. Concentration-response curves of bronchial preparations to ACh did not differ significantly among three groups consisting of the control, IAR and LAR. However, the contractile response of bronchiolar preparations to ACh was significantly greater in the LAR group when compared to the control and IAR groups at the concentrations of ACh ranging from 10(-6) to 3 x 10(-4) M (p < 0.01). SQ 29548, a receptor antagonist of thromboxane A2 and prostaglandin D2 (PGD2), inhibited LAR-induced hyperresponsiveness to ACh in a concentration dependent fashion. The bronchiolar preparations obtained from dogs showing LAR contained a significantly higher amount of PGD2 than those obtained from dogs showing IAR alone (p < 0.01, n = 6). These results suggest that LAR is associated with hyperresponsiveness of peripheral airway smooth muscle to ACh, and this augmented response to ACh mediates via PGD2 released during LAR. PMID- 8508058 TI - A brief history of cardiac pacing. PMID- 8508059 TI - Surgical repair of ventricular aneurysms. Early results with Cooley's technique. AB - Using bovine pericardium instead of Dacron for grafting, we performed ventricular endoaneurysmorrhaphy (Cooley's technique) in 13 patients with postmyocardial infarction left ventricular aneurysm. Twelve patients were men and 1 was a woman; their ages ranged from 38 to 67 years (mean, 51.2 +/- 11.4 years). Eight patients had large anterolateral aneurysms, 4 had apical aneurysms, and 1 had a false inferior aneurysm. Postoperatively, the mean cardiac index increased from 2.07 +/ 0.50 to 3.09 +/- 0.99 L/min/m2 (p < 0.05), with a mean percentage increase of 50.17% +/- 37.03%. No patient required postoperative mechanical circulatory assistance, and pharmacologic support could be withdrawn soon after surgery. All patients had uncomplicated recoveries and were asymptomatic upon discharge, at a mean time of 9.0 +/- 2.3 days after surgery. We conclude that ventricular endoaneurysmorrhaphy provides excellent initial results, and we believe, through subjective analysis of ventriculograms, that the use of bovine pericardium for grafting produces better functional results than does the use of Dacron. PMID- 8508060 TI - Transseptal approach for mitral valve surgery. A safe alternative when the need calls. AB - Within a 40-month period ending in June 1992, we used the transseptal approach in performing mitral valve surgery on 18 patients. The patients selected had 1 or more of the following indications: small left atrium; adhesions from previous cardiac surgery or rheumatic activity; large, organized left atrial thrombus: the need for concomitant tricuspid valve surgery; or any combination of these factors. We made the septal incision in the long axis of the fossa ovalis and extended it anteriorly and posteriorly, taking care not to injure either the aortic root or the coronary sinus. In 15 patients, we easily obtained good mitral exposure; in 3, exposure was still difficult. One patient died, but the cause of death was not related to the surgical approach. Although none of our patients had early postoperative cardiac arrhythmias, the small number in our series and the short follow-up time prevent us from predicting the effect of this incision on late postoperative cardiac arrhythmias. Therefore, we recommend limiting the transseptal approach to complex reoperations and to operations necessitating right atriotomy for concomitant procedures. It is also very useful in patients with a large, organized left atrial thrombus. Under these conditions, we conclude that using the transseptal approach for mitral valve surgery is a simple, safe, and time-saving technique. PMID- 8508061 TI - An ex vivo model for the reperfusion of explanted human hearts. AB - A model of an ex vivo-reperfused human heart was developed by using a modified Langendorff coronary perfusion circuit. The technical and physiologic aspects of reestablishing myocardial contractility are described. Preliminary studies were conducted in animals. In the present study, we obtained 12 human hearts that had been arrested with cardioplegic solution and excised from cardiac transplant recipients. The perfusate contained type-specific human donor red blood cells in a lactated Ringer's solution containing 5% dextrose. Myocardial contractility was successfully reestablished in 11 hearts and sustained for an average of 98 minutes (range, 79 to 180 minutes) at a coronary perfusion pressure of 80 mmHg. Left ventricular contraction pressures reached 40 mmHg (against intraventricular balloons at an internal pressure of 50 to 75 mmHg). Partial oxygen pressure (PO2) dropped significantly across the empty beating myocardium (from 498 +/- 40 mmHg to 219 +/- 53 mmHg [mean +/- SD]), but no significant change in hemoglobin saturation was observed. Myocardial failure generally stemmed from edematous changes leading to progressive impairment of myocardial relaxation. The intracoronary insertion of over-the-wire catheters did not adversely affect myocardial function. In conclusion, an ex vivo-supported human heart model has been developed that may have a number of applications, including the preclinical evaluation of new interventional diagnostic and therapeutic techniques aimed at the coronary circulation, and the investigation of myocardial mechanics, preservation, and metabolism. PMID- 8508062 TI - Right thoracotomy revisited. AB - From September 1991 through August 1992, 38 patients (34 female and 4 male) underwent mitral valve surgery through a limited right anterior thoracotomy. The ascending aorta was easily cannulated for arterial return in all patients. Although there was no operative mortality, 8 patients required reoperation for bleeding, usually associated with the site of chest-wall puncture for the left atrial pressure line and epicardial pacing wires, a problem that we were able to correct. Right lower lobe collapse occurred in 2 patients, but the lungs were fully expanded in all patients before hospital discharge. We believe that a return to this older surgical approach is particularly suited to young patients and provides the important advantages over median sternotomy of superior mitral valve exposure and a cosmetically acceptable scar. PMID- 8508064 TI - High-risk angioplasty. Coarctation of the aorta after Norwood Stage 1. AB - This report describes 2 patients with hypoplastic left heart syndrome who developed severe coarctations of the aorta after Norwood Stage I procedures and subsequently survived recurrent ventricular fibrillation during successful percutaneous angioplasty. Although ventricular fibrillation has not been associated with hypoplastic left heart syndrome, postoperative Norwood Stage I, or angioplasty of isolated coarctations of the aorta, we believe that the complex physiology of our patients created conditions that precipitated ventricular tachycardia and ventricular fibrillation. We strongly recommend that follow-up of infants with hypoplastic left heart syndrome after Norwood Stage I operations be meticulous; that even mild coarctation be treated aggressively, to avoid progression to high-risk situations; and that interventionalists be prepared to manage malignant ventricular dysrhythmias whenever postoperative Norwood Stage I patients undergo percutaneous angioplasty for coarctation of the aorta. PMID- 8508063 TI - The arterial thrombotic process and emerging drugs for its control. AB - Unabated, the arterial thrombotic process continues to be a major challenge in the management of acute coronary artery disease. Pharmacologic and mechanical revascularization therapies, which have proliferated over the last decade, remain impeded by arterial thrombosis and its clinical sequelae. New antithrombotic drugs aimed at specific points in the arterial thrombotic process offer the potential for substantial improvements in the management of coronary artery disease. The use of these agents as a mainstay of patient care is becoming a reality as controlled clinical studies test their safety and potential benefits. PMID- 8508065 TI - Adventures in perioperative myocardial ischemia. PMID- 8508066 TI - Fungal infection in a dissecting aneurysm of the thoracic aorta. AB - We describe a 54-year-old man who had an ascending aortic prosthetic graft and a porcine aortic valve prosthesis that were infected by Candida albicans. This infection led to the formation of a dissecting false aneurysm of the remaining transverse and entire descending thoracic aorta, and the man was admitted to our hospital for surgical treatment in February of 1991. Staged in situ graft replacement was performed using Borst's "elephant trunk" repair for the proximal aortic reconstruction and an open distal anastomosis technique for the distal repair. Candida albicans in the residual prosthetic graft was identified, and therapy with high-dose liposomal amphotericin B was initiated. The use of liposomal amphotericin B reduces the incidence of adverse effects and allows administration of higher doses than those possible with conventional amphotericin B therapy. Lifelong antifungal therapy is recommended for patients with C. albicans infection of prosthetic aortic grafts. PMID- 8508067 TI - Iliac arteriovenous fistula due to spinal disk surgery. Causes severe hemodynamic repercussion with pulmonary hypertension. AB - We present a case of a 46-year-old man with a pulsatile mass in the left inferior abdominal quadrant that irradiated a continuous murmur extending to the left lumbar region. Despite an 8-year history of cardiomegaly, he appeared to be asymptomatic except for the mass and could recollect no traumatic injury or surgery that might have caused it. Near the vertebral column, we found a small scar, the result of spinal disk surgery 11 years before. Following chest radiography and electrocardiography, we located the suspected arteriovenous fistula by selective angiography of the aorta and its branches: a communication of the left iliac artery with the left iliac vein had resulted in a very large left-to-right shunt and a severely dilated inferior vena cava. We then divided and isolated the arterial segment containing the fistula, but left this segment in continuity with the left iliac vein by over-sewing both ends. To avoid injury to surrounding structures, dissection was limited to the area of maximal thrill. Hemodynamic improvement was immediate, and the postoperative course was uneventful. At the present time, almost 3 years postoperatively, the patient is asymptomatic. PMID- 8508068 TI - Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma. AB - We describe a 35-year-old man who had a pulmonary embolism with thrombosis of the inferior vena cava, apparently resulting from compression by a hepatic hemangioma. The diagnosis of pulmonary embolism was confirmed by pulmonary angiography; however, the hemangioma was detected only incidentally, as a hyperechoic mass, during an echocardiogram for intracardiac thrombosis. Abdominal sonography, computed tomography, celiac angiography, technetium 99m-labeled red blood cell scintigraphy, and ultrasound-guided liver biopsy all assisted in the diagnosis of hepatic hemangioma and its compression of the inferior vena cava. Because of the multisegmental and perihilar involvement of the tumor, surgery was not performed. For dissolution of the clots, the patient was given thrombolytic therapy followed by heparin administration. He was then placed on long-term warfarin therapy and is well after 5 years; the size of the hemangioma is unchanged. Cases of pulmonary embolism due to diseases of the upper abdominal organs are rare and probably underestimated. This case stresses the need for a systematic investigation of the abdomen when a pulmonary embolism is present without evidence of deep vein thrombosis. PMID- 8508069 TI - Myocardial dysfunction and mitral valve prolapse: a new physiologic concept. PMID- 8508070 TI - Who should pay the cost of clinical research? PMID- 8508072 TI - Undersea and Hyperbaric Medical Society Annual Scientific Meeting. 7-10 July 1993. Halifax, Nova Scotia. Program and abstracts. PMID- 8508071 TI - Therapeutic options for coronary occlusions secondary to chest trauma. PMID- 8508073 TI - Abdominal MR imaging following antegrade air introduction into the intestinal loops. AB - Air was used to distend the gastrointestinal tract and act as a contrast medium to effectively delineate the other abdominal organs/masses and to outline intraluminal or mural lesions. We used a nasogastric tube to introduce air into the stomach. Metoclopramide was administered to propel air throughout the gastrointestinal tract. Bowel peristalsis was then controlled by scopolamine butylbromide. Most of the alimentary tract could be distended by air. The normal bowel walls were barely visible between intraluminal signal-void air and extraluminal high-signal fat. Intraluminal tumor, wall thickening, and adjacent structures could be clearly delineated. PMID- 8508074 TI - Retrograde air insufflation in MRI: a technical note. AB - Retrograde air insufflation was employed to distend the colon and the ileum in 18 patients and five volunteers for magnetic resonance examination. Good and moderate marking of the ileum was obtained in 18 cases. The colon was nearly completely distended in every case. Intraluminal tumor, mural thickening, and extraluminal lesion were outlined by intraluminal air and surrounding air distended bowel. This study shows that retrograde air insufflation is a useful method to mark the colon and most parts of the ileum. PMID- 8508075 TI - Contrast enhancement of the gastrointestinal tract on MR images using intravenous gadolinium-DTPA. AB - Gadopentetate dimeglumine was administered intravenously to 16 patients undergoing abdominal magnetic resonance (MR) imaging. T1-weighted and fat suppressed T1-weighted images were acquired before and after intravenous administration of 0.1 mmol/kg gadopentetate dimeglumine. The stomach, small bowel, and colon were analyzed regarding the presence and relative intensity of contrast enhancement. Diffuse enhancement of the gastrointestinal tract wall was observed in all patients following contrast material administration. Such enhancement was most conspicuous on fat-suppressed T1-weighted images. Quantitative measurements indicated that the wall of the gastrointestinal tract enhanced approximately 100% with gadopentetate dimeglumine. This study demonstrates that enhancement of the normal gastrointestinal tract occurs routinely when intravenous gadopentetate dimeglumine is administered, and such enhancement should not be considered indicative of gastrointestinal pathology. Furthermore, it suggests the potential utility for using intravenous rather than orally administered contrast agents to provide enhancement of the gastrointestinal tract on MR images. PMID- 8508076 TI - Radionuclide esophageal transit test: detection of esophageal dysmotility and reflux in noncardiac chest pain. AB - Thirty-one patients with substernal chest pain but with normal coronary angiographic findings and 25 normal volunteers were included in our study. Esophageal motility--including esophageal mean transit time (MTT), residual fraction (RF), and retrograde index (RI) of the two groups--were evaluated by the radionuclide esophageal transit test. The results showed that among patients with noncardiac chest pain (NCP), 48% have a longer MTT, 39% have a higher RF, and 58% have a higher RI than normal volunteers. We found that esophageal disorders are a common source of noncardiac chest pain, and that radionuclide esophageal transit test is a simple noninvasive screening method to detect esophageal dysmotility or gastroesophageal reflux in such cases. PMID- 8508077 TI - Primary esophageal lymphoma in AIDS. AB - In a patient with acquired immunodeficiency syndrome (AIDS) and primary esophageal lymphoma, esophagography and computed tomography (CT) demonstrated a large ulcerated mass involving the distal esophagus. Although rare, the diagnosis of esophageal lymphoma should be considered in patients at risk for AIDS when the radiologic findings are not typical for infectious esophagitis or Kaposi's sarcoma. PMID- 8508078 TI - Staphylococcal esophagitis causing giant ulcers. AB - A 29-year-old woman with Hodgkin disease developed odynophagia while receiving chemotherapy. Large esophageal ulcers due to staphylococcal infection of the mucosa were visualized by endoscopy and radiography. This unusual bacterial esophagitis represents another potential cause of giant esophageal ulcerations. PMID- 8508079 TI - Cervical esophageal web associated with a patch of heterotopic gastric mucosa. AB - Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed. PMID- 8508080 TI - Isolated gastric varices: ultrasound detection. AB - Isolated gastric varices (IGV) (resulting from varying etiologies) were diagnosed in six patients using ultrasound examination of the wall of the fluid-filled stomach. Small gastric varices are seen as circular or linear anechoic channels within the gastric wall without a significant intraluminal projection. Large varices are seen as anechoic, lobulated "bulging masses" projecting into the fluid-filled lumen of the stomach. Doppler technique assists in confirming the vascular nature of these lesions and thus avoids confusion with other hypoanechoic lesions of the gastric wall. The technique is simple, noninvasive, and extremely useful in diagnosing IGV in patients investigated for recurrent undiagnosed gastrointestinal bleeding. PMID- 8508081 TI - Gastric liposarcoma: CT appearance. AB - Two cases of liposarcoma of the stomach are described. At computed tomography (CT) the neoplasms showed features of an aggressive malignant tumor, with no fatty values within. We discuss the differential diagnosis of such lesions and conclude that, although rare, liposarcoma should be considered as a possible diagnosis when a large exophytic gastric mass is detected at CT. PMID- 8508083 TI - Carcinoma of the ampulla of Vater: sonographic and CT diagnosis. AB - Twenty patients with carcinoma of the ampulla of Vater were studied with sonography (N = 9) or both sonography and CT (N = 11). The tumor was shown by sonography in 16 patients (80%) as a small, round or oval, fairly well delineated mass in between the dilated distal common bile duct and duodenum which was delineated owing to luminal fluid or gas (N = 13); or as a polypoid mass within the dilated distal common bile duct resulting in abrupt obstruction (N = 3). In the remaining four patients, the mass was not delineated. Bile ducts were dilated down to the level of mass or ampullary region in all cases (100%), while the pancreatic duct was dilated in five cases (45%). We believe that sonography is the technique of initial choice in the diagnosis of carcinoma of the ampulla of Vater by identifying the mass at the distal end of the dilated common bile duct and/or pancreatic duct. PMID- 8508082 TI - Spontaneous duodenal fistula due to hepatic hydatid cyst. AB - Communication of a hepatic hydatid cyst to the duodenum appears to be extremely rare. This is the first case described in the imaging literature of hepatic echinococcosis fistulized to the duodenum studied by computed tomography. PMID- 8508084 TI - Carcinoid of the intrahepatic ducts. AB - Carcinoid tumors of the biliary tree are rare. To the best of our knowledge, this is the first reported case of an intrahepatic ductal carcinoid and the thirteenth reported case of biliary carcinoid. The radiographic appearance is variable. A brief review of the previously described cases is presented. PMID- 8508085 TI - Villous adenoma of the common bile duct. AB - A villous adenoma of the common bile duct (CBD) causing obstructive jaundice was demonstrated by sonography and ERCP in a 34-year-old man. The radiological and clinical features of this rare tumor are herein presented. PMID- 8508086 TI - MR imaging of traumatic hepatic laceration: evaluation and course of healing after surgery. AB - Six patients with hepatic laceration underwent magnetic resonance imaging (MRI) at 0.5T. Acute hepatic laceration was slightly hypointense on T1-weighted spin echo (SE) image, and hyperintense on T2- and proton-weighted SE images. Subacute laceration was heterogeneously intense on T1-weighted image and hyperintense on T2- and proton-weighted images. Consistent changes in signal intensity of postoperative hepatic laceration were observed. On T1-weighted image, the signal intensity at first increased and then decreased from periphery to the center. On the T2- and proton-weighted images, the laceration was uniformly hyperintense relative to the liver prior to the appearance and growth of a hypointense ring at its periphery. The appearance of the above changes in signal intensity was also observed in postoperative recurrent hemorrhage. The postoperative biloma had none of the above changes in signal intensity. Our cases show that MRI is effective in the evaluation of hepatic laceration and in the assessment of the course of healing after operation. PMID- 8508087 TI - Bile leakage as a complication of liver biopsy in liver transplants. AB - Four liver transplant recipients with intrahepatic bile duct leakage following liver biopsy are described. Two patients were clinically suspected of having a bile leak, one of whom had bile peritonitis. All four patients had elevated liver enzyme levels. In three patients, cholangiography showed contrast media leakage into the peritoneum through the needle biopsy tract; one leak was totally intraparenchymal. All patients had varying degrees of biliary obstruction. The differential diagnosis of bile leakage post-transplantation should include recent liver biopsy. PMID- 8508088 TI - Radiological findings of human fascioliasis. AB - Fasciola hepatica is a trematode of herbivorous mammals. Humans are accidentally infected by the ingestion of water or raw aquatic vegetables contaminated with the metacercaria. Radiological findings of six patients with fascioliasis (five hepatic fascioliasis, one biliary fascioliasis) were analyzed. The diagnosis was based on serological testing and/or histopathologic findings of eosinophilic abscess in five patients and identification of the adult worm in one patient. The characteristic radiological features of hepatic fascioliasis were (1) cluster of microabscesses arranged in tract-like fashion (burrow tract), (2) subcapsular location of the hepatic lesions, and (3) very slow evolution of the lesion on follow-up examinations. In biliary fascioliasis, there were multiple conglomerated filling defects in the common bile duct. The authors believe that the demonstration of these features, together with peripheral eosinophilia or eosinophilic aspirate from the hepatic lesion, is very helpful in making the correct diagnosis. PMID- 8508089 TI - Small bowel enema and diagnosis of chronic nonischemic disturbance of superior mesenteric venous blood flow. AB - Chronic nonischemic disturbance of mesenteric venous blood flow is reported in 11 patients with a mean age of 19 years. This entity, rarely discussed in the literature, is different from acute thrombosis and chronic thrombotic forms with portal hypertension or hypercoagulopathy. In eight patients this syndrome was secondary to organic lesions of different origin: mesenteric vein squeezed by fibrous bands or an abnormal jejunal artery (four cases), lymphoma involving the distal superior mesenteric veins (three cases), hemangioma causing microthrombi (one case). In three patients no etiology or predisposing factor was found. All patients presented with rectal hemorrhage. Small bowel enema showed a constant pattern in 11 patients: small nodules, modified by compression or peristalsis, involving the mesenteric border of the jejunoileal segment, and associated with thick, straight but regular folds. Mesenteric varices were suspected and led to angiographic studies which were normal in three cases, confirmed varices in eight cases, and thrombosis in four cases. Laparotomy was normal in three cases and established the etiological diagnosis in eight cases. Varices were shown in six cases. Arteriography and laparotomy were unable to reach a complete diagnosis. PMID- 8508090 TI - Small intestinal phytobezoars: sonographic detection. AB - Three cases of small intestinal phytobezoar, suggested by sonography and later confirmed at surgery, are reported. Sonographic findings of bezoar were intraluminal mass presenting as an arc-like surface echo casting clear posterior acoustic shadow within the lumen of the dilated small bowel. Compression of the mass with a transducer induced fluid shift around the mass. We propose that diagnosis of bezoars can be suggested on the basis of sonographic findings. PMID- 8508091 TI - Roundworm obstruction: sonographic diagnosis. AB - We describe the sonographic findings in five pediatric patients with roundworm obstruction. All patients were referred with a clinical diagnosis of acute appendicitis. On ultrasonography (US), an individual worm, when viewed along its longitudinal axis, appeared as a hypoechoic tubular structure with well-defined, echogenic walls. Frequently, the individual body segments could be distinctly visualized. The alimentary canal of the worm was seen either as a single central echogenic line (when in a collapsed state) or as two parallel hyperechoic bands with a hypoechoic center (when distended). When examined transaxially, the individual worm resembled a target with its circular, echogenic body wall and its central dot-like alimentary canal. On prolonged scanning, the worms always showed curling movements. In two patients, a bolus of worms mixed with fecal matter and air produced an unusual appearance of a complex, echogenic mass (helminthoma). Although, an individual worm occasionally resembled an inflamed appendix, visualization of the alimentary canal and individual body segments along with its curling movements helped establish the correct diagnosis. All patients promptly responded to a hypertonic saline enema and no patient was subjected to surgery. Sonographic findings in roundworm obstruction are fairly characteristics to advocate the routine use of sonography for diagnosing this entity. PMID- 8508092 TI - Peritoneal fluid in children with intussusception: its sonographic detection and relationship to successful reduction. AB - A retrospective review of the abdominal/pelvic ultrasound (US) examinations in 21 consecutive children with intussusception proven on barium enema was performed to determine what is the incidence of US detected peritoneal fluid in this population and to see if the rate of reduction was different in this subset. Twelve of the 21 children (57%) had free fluid demonstrated with US. Eight of these 12 (67%) had successful reduction. Six of the nine children (67%) without free fluid were also successfully reduced. PMID- 8508093 TI - Peritoneal mesothelioma: sonographic findings in nine cases. AB - Ultrasonographic findings in nine cases of peritoneal mesothelioma are presented. The most common findings were sheet-like or nodular peritoneal thickening, soft tissue masses, fixation of the intestinal loops, mesenteric thickening, and minimal ascites which was disproportional to the degree of tumor dissemination. The authors found that abdominal sonography, using 3.75-7.5 MHz transducers, is a useful imaging method for diagnosis of peritoneal mesothelioma in high-risk groups. PMID- 8508094 TI - Peliosis of the spleen with intraperitoneal hemorrhage. AB - We encountered a patient with steroid-related peliosis of the spleen, a rare disease characterized by multiple blood-filled cavities in the splenic parenchyma, with spontaneous intraperitoneal hemorrhage. The ultrasonographic, computed tomographic, and angiographic images were compared with pathologic findings of the material obtained surgically. PMID- 8508095 TI - Mesenteric actinomycosis. AB - We report a case of abdominal actinomycosis demonstrated on computed tomography (CT) as an isolated mesenteric mass with radiating linear and nodular densities. The lesion mimicked a mesenteric tumor with desmoplastic reaction. The clinical and radiological features of this uncommon entity are reviewed. PMID- 8508096 TI - Cecal volvulus: the CT whirl sign. AB - Cecal volvulus is a rare, but potentially fatal, cause of intestinal obstruction. As computed tomographic (CT) scanning is often the initial diagnostic test in patients with acute abdominal pain, we reiterate the importance of the "whirl sign" in diagnosing intestinal volvulus. We report the first description of the CT diagnosis of cecal volvulus. PMID- 8508097 TI - CT appearance of calcified tumor thrombus in the inferior vena cava. AB - We report the unusual occurrence of calcified tumor thrombus in the inferior vena cava (IVC) in a patient with renal cell carcinoma diagnosed by computed tomography (CT). PMID- 8508098 TI - Urinoma secondary to surgical spinal fusion: radiologic diagnosis and treatment. AB - We have presented a case of urinoma secondary to ureteral injury during spinal fusion via retroperitoneal approach demonstrated by CT. The presumed diagnosis of urinoma was confirmed and treated by interventional radiologic techniques. PMID- 8508099 TI - Actinomycosis of the retroperitoneum and an extremity: CT features. AB - A patient presenting with thigh and flank masses and back pain for 3 months proved to have actinomycosis involving the retroperitoneum and quadriceps muscle. Retroperitoneal involvement without intraperitoneal disease is rare. Computed tomography (CT), however, showed disease transgressing adjacent anatomic compartments with direct extension through the body wall and involvement of adjacent bony structures which is characteristic of actinomycosis. PMID- 8508100 TI - Cystadenoma of the seminal vesicle: US and CT findings. AB - Ultrasonographic (US) and computed tomographic (CT) features of a cystadenoma of the seminal vesicle are presented. PMID- 8508101 TI - Excess incidence of known non-insulin-dependent diabetes mellitus (NIDDM) in Hispanics compared with non-Hispanic whites in the San Luis Valley, Colorado. AB - Non-insulin-dependent diabetes mellitus is between two and five times more prevalent among Hispanic Americans than among non-Hispanic whites (NHW). Incidence data for Hispanic populations will help to determine whether this excess prevalence is due to increased incidence, survivorship, or other factors. Incident cases were identified through concurrent surveillance of all local medical practices from 1983 to 1988 in two southern Colorado counties in which the population was 46% Hispanic. All identified subjects were invited for an oral glucose tolerance test. Among the subjects who attended clinic, 83% were confirmed as having diabetes, using WHO criteria. The standardized average annual incidence rates per 1000 for confirmed non-insulin-dependent diabetes, accounting for nonresponse, were 3.7 and 1.6 for Hispanic and NHW males, and 4.5 and 1.2 for Hispanic and NHW females, respectively. The age and nonresponse adjusted rate ratio comparing Hispanics to NHWs was 3.1 (95% CI: 2.3-4.2), indicating a significant excess risk of diabetes incidence for the Hispanic population in southern Colorado. Peak age-specific incidence among Hispanics occurred in persons 50 to 59 years old, a decade earlier than among NHWs. These results are consistent with data from the Mexican-American population in Texas and suggest that the previously observed excess in diabetes prevalence is due to higher incidence rates. The earlier age-specific peak in incidence has also been observed in Mexican-American and American Indian populations, suggesting that risk factors may operate at earlier ages. PMID- 8508102 TI - A comparison of three methods for assessing Amerindian admixture in Mexican Americans. AB - Epidemiologic studies have revealed that Mexican Americans experience an excess of non-insulin-dependent diabetes mellitus, gallbladder disease, and obesity relative to non-Hispanic whites. It has been hypothesized that the greater susceptibility of Mexican Americans to these disorders may be related to their greater degree of Amerindian genetic admixture. We evaluate the comparability of three different methods of assessing individual genetic admixture in Mexican Americans. Subjects were enrolled as part of the San Antonio Heart Study and were examined between 1979 and 1988 (n = 3301). Three different methods were used to assess Amerindian admixture: we queried subjects about their ancestors' ethnic origin, we measured subjects' skin color, and we estimated genetic admixture directly by analysis of polymorphic blood markers. These measures were generally poorly correlated with each other, with the highest correlations observed between skin color and proportion of Mexican-origin grandparents. In men, none of these three measures of genetic admixture was associated with the prevalence of diabetes, gallbladder disease, or obesity. In women, consistent positive associations were observed between admixture and all three diseases, regardless of the admixture measure used (ie, disease prevalence was higher among women with more Amerindian admixture). In both sexes, height was negatively correlated with all three measures of admixture, and admixture was also significantly correlated with body mass index and central adiposity in women. These data suggest that the three measures considered may assess different dimensions of admixture, but that for epidemiologic research, no one may be claimed to be superior to the others. PMID- 8508103 TI - An ultrasound survey of gallbladder disease among Mexican Americans in Starr County, Texas: frequencies and risk factors. AB - The Mexican-American population of south Texas has been shown previously to have elevated frequencies of gallbladder disease, based on medical history. In the present study, ultrasonography was employed to screen 1004 randomly selected individuals aged 15 to 74 years. Among women, the frequency of previous cholecystectomy was 10.0%; the frequency of stones on ultrasound was 12.2%. In men, the respective frequencies were 1.7% and 6.3%. Highest frequencies of gallbladder disease occurred among those aged 45 years or above: 40.2% and 19.2% among women and men, respectively. Non-insulin-dependent diabetes mellitus, obesity, and hypertension were also markedly elevated in this population. Overall, more than 40% of the population had either gallbladder disease, non insulin-dependent diabetes, obesity, or hypertension. Among those older than 45 years, 70% had one or more of these chronic conditions. Examining the associations of gallbladder disease with other chronic diseases or measures of lipids, lipoproteins, and apolipoproteins demonstrates that factors predictive of or associated with cholecystectomy are different from those for gallstones by ultrasound. Diabetes and obesity show the strongest associations with cholecystectomy among women under 45 years (women with diabetes being 6.8 times as likely to have had a cholecystectomy than those without diabetes). Testing an extensive array of lipid-related measures resulted in no clear patterns, with the possible exception of alpha-lipoprotein and related measures. That the Mexican American population is relatively young and experiencing extremely rapid growth indicates that the burden of chronic disease in general and gallbladder disease in particular will increase dramatically in the coming years. PMID- 8508104 TI - Is the risk of coronary heart disease lower in Hispanics than in non-Hispanic whites? The San Luis Valley Diabetes Study. AB - A less favorable cardiovascular risk factor profile, but paradoxically lower coronary heart disease mortality and prevalence have been reported for Hispanic men compared to non-Hispanic white men. Since mortality and prevalence data are susceptible to bias, the patterns of coronary heart disease incidence, as well as prevalence and mortality, were investigated in a biethnic Hispanic and non Hispanic white population of the San Luis Valley in Colorado. Little evidence was found for lower incidence, prevalence, or mortality due to coronary heart disease among Colorado Hispanics without diabetes. The risk of coronary heart disease among diabetic Hispanics appeared, however, to be approximately 50% lower than among non-Hispanic whites, especially in men. Adjustment for selected cardiovascular risk factors (age, gender, diabetes, hypertension, cigarette smoking, body mass index, and high-density lipoprotein cholesterol and triglycerides levels) did not change this ethnic pattern. The plausible explanations of a lower coronary heart disease risk among diabetic Hispanics, compared to non-Hispanic whites, include both biologic mechanisms and artifacts due to deficiencies of mortality classification or differential access to health care. The existing evidence is insufficient to conclude that the risk of coronary heart disease in the general population differs between Hispanics and non Hispanic whites. The ethnic patterns of coronary heart disease incidence should be investigated further through population-based incidence studies. PMID- 8508105 TI - Mortality after hospitalization for myocardial infarction among Mexican Americans and non-Hispanic whites: the Corpus Christi Heart Project. AB - We compared short- and long-term mortality among 334 Mexican Americans and 348 non-Hispanic whites hospitalized for myocardial infarction in the Corpus Christi Heart Project. Age-adjusted 28-day case fatality rates were 37% and 68% greater among Mexican-American women (6.7%) and men (6.2%) than among their non-Hispanic white counterparts (4.9% and 3.7%). Age-adjusted all-cause mortality rates over the next 25-month period, among those who survived the initial 28 days, were similar among Mexican-American and non-Hispanic white women (17.8% and 18.1%), but were 70% higher among Mexican-American men than among non-Hispanic white men (17.4% and 10.2%, respectively). Age-adjusted 25-month coronary mortality rates among initial 28-day survivors were 40% greater among Mexican-American women than among non-Hispanic white women (12.5% vs 9.0%), and 129% greater among Mexican American men than among non-Hispanic white men (11.4% vs 5.0%, respectively). Thus, nearly all measures of post-myocardial infarction mortality indicated a survival disadvantage for Mexican Americans compared to non-Hispanic whites. PMID- 8508106 TI - Acute myocardial infarction and coronary heart disease mortality among Mexican Americans and non-Hispanic whites in Texas, 1980 through 1989. AB - We calculated acute myocardial infarction and chronic coronary heart disease mortality rates for Mexican Americans and non-Hispanic whites in Texas for the 10 year period from 1980 through 1989 in an examination of ethnicity-related differences in death rates and trends according to vital statistics for the state of Texas. During the study period, acute myocardial infarction mortality decreased significantly in all four sex-ethnic groups, between 5.1% and 7.4% per year. Chronic coronary heart disease mortality rates decreased less, but significantly, for women in both ethnic groups, decreasing 3.4% and 1.8% per year for Mexican-American and non-Hispanic white women, respectively. We found no significant trend of changes in chronic coronary heart disease mortality rate among men in either ethnic group. For both acute myocardial infarction and chronic coronary heart disease mortality, rates were significantly lower among Mexican-American men than among non-Hispanic white men. Age-adjusted rate ratios for Mexican-American men in relation to non-Hispanic white men were 0.78 (95% CI: 0.65-0.93) and 0.75 (0.65-0.86) for acute myocardial infarction and chronic coronary heart disease mortality, respectively. No significant ethnicity-related mortality difference was seen among women. This previously observed interaction of ethnicity and sex in relation to coronary heart disease mortality remains unexplained. Despite apparently adverse cardiovascular risk factor profiles, Mexican Americans have acute myocardial infarction and chronic coronary heart disease mortality rates equal to or lower than their non-Hispanic white counterparts on the basis of death certificate data. This paradox deserves further attention. PMID- 8508107 TI - Cardiovascular and other chronic diseases among Mexican Americans: the emerging picture. PMID- 8508108 TI - Acculturation and hypertension in Mexican Americans. AB - In this analysis, we employ data from the Hispanic Health and Nutrition Examination Survey to examine the association between level of acculturation into the larger society and rates of hypertension in Mexican Americans. Analyses conducted separately by gender in three broad age groups (ages 20 to 39, 40 to 59, and 60 to 74 years) fail to indicate a linear effect of acculturation on hypertension after controlling for age, education, marital status, employment, smoking, alcohol consumption, and body mass index. A nonlinear hypothesis was subsequently examined and found partial support among middle-aged men. Other things equal, middle-aged men at the middle of the acculturation continuum have significantly higher rates of hypertension than persons at the low end of the continuum. Lower rates are also observed among men at the high end of the acculturation continuum, but these rates are not significantly lower than those among men in the middle acculturation group when other variables are controlled. These findings for middle-aged men support an "acculturative stress" model that suggests that stress is higher at the middle of the acculturation continuum. Research on the influence of acculturation on health outcomes should go beyond simply examining linear effects to investigate the viability of nonlinear effects. PMID- 8508109 TI - Ethnic differences in mortality from cerebrovascular disease among New Mexico's Hispanics, Native Americans, and non-Hispanic whites, 1958 through 1987. AB - We analyzed vital statistics data collected from 1958 through 1987 to determine time trends and ethnic differences in cerebrovascular disease mortality rates in New Mexico's Hispanic, Native American, and non-Hispanic white populations. Over the 30-year period of our study, cerebrovascular disease mortality rates decreased in all three major ethnic groups in the state, comparable to national trends. We found that Native Americans of both sexes had the lowest cerebrovascular disease mortality rates, followed by Hispanics, during the initial 25-year span of our data. In the most recent 5-year period that we examined, 1983 through 1987, Hispanics had the highest cerebrovascular disease mortality rates of the three groups. Our data suggest that Hispanics in New Mexico are now at higher risk for cerebrovascular disease-related mortality than are non-Hispanic whites, and that prevention strategies aimed at decreasing cerebrovascular disease rates should be focused on this segment of the state's population. PMID- 8508110 TI - Thirteen essentials of a quality initiative. PMID- 8508111 TI - Quality outcomes in primary care: nurse practitioners equal/higher than physicians. PMID- 8508112 TI - Formats for indicators: one right way? PMID- 8508113 TI - Selecting computer hardware. PMID- 8508114 TI - Exposure flow chart. PMID- 8508115 TI - Effective action planning. PMID- 8508117 TI - Brainstorming. PMID- 8508116 TI - Hypothermia in the OR. PMID- 8508119 TI - The potential demise of staff development departments. PMID- 8508118 TI - How to select a quality continuing education offering. PMID- 8508120 TI - Friends of nursing. PMID- 8508121 TI - Linking staff development to the organization's goals. PMID- 8508122 TI - Being yourself while serving others. PMID- 8508124 TI - Developing clinical educators. PMID- 8508123 TI - Certification in staff development/continuing education: plan for success. PMID- 8508125 TI - [Genetic effects upon cloning heterologous DNA in yeast artificial chromosomes]. PMID- 8508126 TI - [The role of NR-1 protein, specific for heterochromatin, during compactization of euchromatin regions, upon mosaic type variegation]. PMID- 8508128 TI - [The role of carrier sympatry and allopatry for functioning of foci of communicable diseases]. PMID- 8508127 TI - [Adaptive of repair, induced by low doses of gamma-radiation, in repair-defective human cells]. PMID- 8508129 TI - [Radioresistance of mollusk populations from water reservoirs with various levels of radioactive contamination]. PMID- 8508130 TI - [Detection of gamete mutations in the hypervariable region of human DNA for genetic monitoring]. PMID- 8508131 TI - [Effect of the "Star" gene on the rate of melanoblast migration in silver fox (Vulpes vulpes) embryos]. PMID- 8508132 TI - Prenatal diagnosis of Sanfilippo syndrome type A by early amniocentesis. AB - Early amniocentesis performed at 13 weeks gestation was utilized to obtain amniocytes for culture. Sonicates of cultured amniocytes were used to measure heparin sulfamidase activity for assessment of the status of an at risk pregnancy for Sanfilippo syndrome, type A. The heparin sulfamidase activity was not detectable in cultured amniocytes of the fetus at risk while another enzyme, N acetylglucosamine 6-sulfatase, was comparable to that of the control. Following termination of the pregnancy, various tissue from the fetus were used for assay of both enzymes. The sulfamidase activity was not detectable in any of the fetal tissue while the 6-sulfatase activity was present in all fetal tissue but varied in activity depending on the type of tissue. Cultured fetal skin and brain contained the highest enzyme activity while skin and liver contained the lowest. PMID- 8508133 TI - Adriamycin-induced oxidative stress in rat central nervous system. AB - Adriamycin elicited a stimulation of rat central nervous system lipid peroxidation, both in vivo and in vitro, as evidenced by the increase in the content of thiobarbituric acid reactants, which was found to be NADPH-dependent. The antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were seen to decrease on exposure to adriamycin (1 mg/kg for a period of 7 days), together with a significant decrement in the GSH/GSSG ratio, thus contributing to the oxidative insult to the tissue. The in vitro addition of GSH or vitamin E to brain homogenates offered protection against adriamycin-induced lipid peroxidation, suggesting that supplementation with these antioxidants could improve the therapeutic value of the drug. PMID- 8508134 TI - The fate of phosphatidylethanolamine formed by decarboxylation in rat brain mitochondria. AB - In the liver, the synthesis and the decarboxylation of phosphatidylserine (PS) are a part of a metabolic cycle forming choline from serine. Yet, in the brain, the methylation of PE to phosphatidylcholine is a minor path. Therefore it is possible that the decarboxylation of PS has different biological meanings in the two organs. In this paper, we follow the formation and the fate of radioactive PE; to this purpose, we load brain mitochondria with PS by incubating cell homogenates with labelled serine in base-exchange conditions. Then, we isolate mitochondria and incubate them for PS decarboxylase. We also subfractionate mitochondria to investigate the distribution of PE in inner and outer membranes. We conclude that newly formed PE slowly moves from its site of synthesis (inner mitochondrial membranes). Besides, it reacts better with TNBS and with FLA than the pre-existing PE. This suggests that the newly-synthesised lipid does not mix quickly with the rest of mitochondrial PE. Therefore, our data demonstrate that the fate of PE formed through the decarboxylation path in the brain is different from that reported for the liver where newly-formed PE is rapidly exported to outer mitochondrial membranes. PMID- 8508135 TI - Effects of estrogen-progestin replacement therapy on plasma beta-endorphin levels in menopausal women. AB - Serum beta-endorphin, LH, FSH, estradiol (E2) and progesterone (P) were measured in postmenopausal women before and after four different estrogen-progestin replacement therapies. Our result showed that serum E2 increased significantly and serum LH and FSH decreased significantly after all treatments. Serum P levels were similar before and after all treatments. Serum beta-endorphin levels increased significantly after cyclic administration of estrogen-progestin, but not after continuous administration of E2. We conclude that the frequently observed beneficial effects of estrogen-progestin replacement therapy on behavior and mood in postmenopausal women may be related to changes in peripheral opioid levels. PMID- 8508136 TI - Fluorescein 5'-isothiocyanate binds to the coenzyme and not to the substrate binding site of lamb liver 6-phosphogluconate dehydrogenase. PMID- 8508137 TI - Relative susceptibility of the thymus and thymocytes to lipid peroxidation. AB - Thymus and thymocytes peroxidizability was studied in well defined conditions where lipid hydroperoxide dependent peroxidation occurs. The results show that: (i) lipid peroxidation is very low in thymocytes notwithstanding the higher content of arachidonic acid; (ii) the amounts of lipophilic chain-breaking antioxidants is higher in thymocytes; (iii) the thymus contains more total lipids and phospholipids. Thus the higher sensitivity to peroxidation of the thymus can be due to the replacement of thymus parenchyma by fatty tissue not correlated to an increase of lipophilic antioxidants. PMID- 8508138 TI - The stability of beta-amyloid precursor protein in nine different cell types. AB - Cell extracts from HeLa, macrophage, glial, C6, PC12, IMR-32, neuroblastoma, CHP 100 and P19 cells were examined for APP and its different derivatives by immunoblotting. When five antibodies (raised against different parts of APP) were used to stain western blots of nine cell extracts, three groups of immunoreactive proteins were observed: high molecular weight-(HMW, 70-125 kDa), medium molecular weight-(MMW, 30-40 kDa) and low molecular weight (LMW, 4-16 kDa). The intensity of immunoreactivity among these three groups of proteins varied in each cell line. The strongest signal for HMW protein was observed in PC 12 cells, the strongest signal for MMW protein was observed in C6 astrocyte cells, and both HMW and MMW protein bands were detected in macrophages and P19 cell lines. LMW protein bands could be detected only by antibody against the carboxyl-terminal part of the APP molecule. These experiments suggest that APP is processed differently in the various cell types. The conversion of APP to beta-peptide may be related to the stability of APP in cells and the understanding of these intermediate steps of APP processing is crucial to the elucidation of Alzheimer's disease. PMID- 8508139 TI - Effects of modified bases in sequence recognition by ClaI endonuclease and ClaI methylase. AB - To understand the functional groups required for sequence recognition, dodecanucleotides containing ClaI sequence in the middle positions with modified bases were synthesized and used as substrates for ClaI endonuclease and ClaI methylase reactions. For the modification, dU, 5-bromo-dU, and dI were used. Km values of the two enzymes were determined for normal and modified oligonucleotides. Our data showed that 5-CH3 groups of the first and second T residues of the hexanucleotide sequence were essential contact points for ClaI methylase. However, ClaI endonuclease was still active without either one of those methyl groups with elevated Km values. Bromine could compensate significantly for the loss of 5-CH3 groups at both position. On the other hand, the 2-amino group of G residue appeared to be an essential contact point for both enzymes. It has been concluded that ClaI endonuclease and ClaI methylase recognize the sequence in different ways. PMID- 8508140 TI - Purification of aspartate aminotransferase from Thermus aquaticus. AB - A method is described for the purification of the enzyme aspartate aminotransferase from the thermophile Thermus aquaticus. The enzyme has been characterized with respect to its molecular weight on SDS PAGE and by amino acid analysis. Attempts to obtain N-terminal sequence data was unsuccessful, presumably due to a blocked N-terminus. The purified enzyme has been shown to be highly thermostable, having a half life of inactivation of about 6 hours at 100 degrees C, and to have a temperature optimum greater than 95 degrees C. PMID- 8508141 TI - Selective elution of subunit 4-containing rat liver glutathione S-transferases using affinity chromatography. AB - Glutathione S-transferase (GST) isoenzymes of rat liver cytosol were purified from a S-hexylglutathione Sepharose affinity column without using S-hexyl glutathione for elution. The method involves an initial elution of GSTs 3-4 and 4 4 from the affinity matrix with 10 mM glutathione in 50 mM Tris-HCl (pH 7.0), followed by the elution of GSTs 1-1, 1-2, 2-2 and 3-3 with 10 mM glutathione in 50 mM Tris-HCl (pH 9.6). These two fractions were then chromatofocused simultaneously to separate the individual GST dimers. The ampholytes used in this process were subsequently removed by ultrafiltration, as the standard techniques (Sephadex G25 column, and dialysis) were not effective. This method provides improved yields and reduced losses of GST activity, by halving the preparation time. PMID- 8508142 TI - Effect of Ca2+ on the binding of Actinobacillus actinomycetemcomitans leukotoxin and the cytotoxicity to promyelocytic leukemia HL-60 cells. AB - The effects of Ca2+ on the binding of Actinobacillus actinomycetemcomitans leukotoxin (LT) to LT-susceptible promyelocytic leukemia HL-60 cells and the consequent cytotoxicity were investigated in comparison with those on LT resistant erythroleukemia K-562 cells. The total amount of LT bound to the HL-60 and K-562 cells, as determined by ELISA using anti-LT rabbit serum, was essentially the same for both cells. The percentage of bound LT decreased in the presence of phosphatidylcholine (PC) was also almost equal for both cells. In contrast, EGTA added in the presence of PC enhanced the decrease of bound LT significantly from HL-60, but not from K-562. By monitoring the fluorescence of Fura-2 and of fluorescein as a measure for the change in intracellular calcium ions ([Ca2+]i) and cytotoxic activity, respectively, we showed that the exposure of HL-60 to LT induced the [Ca2+]i increase followed by the cell death, whereas this was distinctly not the case for K-562. These results indicate that a Ca(2+) dependent LT-binding mechanism is possibly the step characteristic to LT susceptible HL-60 cells. PMID- 8508143 TI - Charge effects on chylomicron clearance in rats. AB - Feeding a diet enriched with cholesterol/cholic acid (CCA) to rats caused defective plasma clearance of labeled chylomicron-like emulsions compared with clearance in chow-fed rats. When heparin was injected 5 min before an emulsion, the clearance of the emulsion in CCA-fed rats was significantly improved, and lipoproteins in the remnant and HDL fractions of plasma became enriched in apolipoprotein E. Injection of lactoferrin or poly-arginine inhibited the removal of emulsion or lymph chylomicron cholesteryl oleate in regular chow-fed rats. Poly-arginine but not lactoferrin inhibited the clearance of emulsion or chylomicron triolein also. The results demonstrate the involvement of charge interactions in both the lipolysis and remnant uptake steps of chylomicron clearance. PMID- 8508144 TI - Oxidative modification of bovine erythrocyte superoxide dismutase by hydrogen peroxide and ascorbate -Fe(III). AB - Exposure of superoxide dismutase to hydrogen peroxide or ascorbate -Fe(III) gives rise to the modification of the enzyme structure and the changes of its function as well as of its immunological property. The structure alterations are especially shown as the loss of the enzyme-bound copper, the production of peptide fragments, the formation of carbonyl groups in the amino acid side chains, the increase in the contents of aspartic acid, glutamic acid and glycine and a decrease in the number of histidine, proline, arginine, lysine, serine and threonine. Accompanying the structure changes, the enzyme lost its catalytic activity. Hydrogen peroxide and ascorbate -Fe(III) exhibited different effects on the structural and functional changes of the enzyme. Furthermore, the bovine superoxide dismutase exposed to hydrogen peroxide or ascorbate -Fe(III) with different kinds of antisera such as antibovine, anticanine, antiporcine and antihuman superoxide dismutase antisera all showed greatly increases in the reactivities. It is proposed that reactive oxygen species may play a role in the building up of circulating immune complexes in autoimmune diseases. PMID- 8508145 TI - Interaction of hydrophobized antiviral antibodies with influenza virus infected MDCK cells. AB - The ability of artificially stearoylated antibodies to influenza virus hemagglutinin and M1 proteins to interfere with influenza infection in MDCK cells has been studied. Both the modified anti-hemagglutinin (polyclonal) and anti-M1 (monoclonal) antibodies neutralize the virus when added before the infection. The effect can be attributed to the interaction of stearoylated antibodies with the virus surface, which is enhanced by fatty acylation (anti-hemagglutinin), or to the antibody uptake in the cell endocytic compartments simultaneously with the virion which permits antibodies to interact with the virus envelope internal antigen (anti-M1). The stearoylated antibodies to hemagglutinin inhibit the virus reproduction being added to the infected cells. This effect is believed to be due to the interaction of the antibodies with newly synthesized hemagglutinin on the cell surface which disturbs the virus budding and assemblage; fatty acylation intensifying this interaction. PMID- 8508146 TI - Purification of aminoacyl-tRNA synthetase kinase activities associated with threonyl- and tyrosyl-tRNA synthetases isolated from Bom:NMRI mouse liver. AB - Aminoacyl-tRNA synthetase kinase activities and aminoacyl-tRNA synthetase activities prepared from postribosomal supernatants of Bom:NMRI mouse liver comigrated through the following purification steps: 1 a) gel filtration on Sephadex G-200, 1 b) chromatofocusing, 2) affinity chromatography on immobilised total tRNA (mixture of tRNA's, specific for all aminoacyl-tRNA synthetases) and 3) affinity chromatography on immobilised tRNA, specific for each of threonyl- and tyrosyl-tRNA synthetases. The purification factors for threonyl- and tyrosyl tRNA synthetases were about 17000x. The purified synthetases showed only one protein band following sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified threonyl- and tyrosyl-tRNA synthetase proteins were found also to possess threonyl- and tyrosyl-tRNA synthetase kinase activities, respectively. The purification of tRNA(Thr) and tRNA(Tyr) as well as a method for the renaturation and identification of threonyl- and tyrosyl-tRNA synthetase activities in protein bands obtained by SDS PAGE are described. PMID- 8508147 TI - Inhibition of Helicobacter pylori colonization by an antiulcer agent, sulglycotide. AB - Sulglycotide, a potent antiulcer agent derived from duodenal mucus glycopeptide through sulfation of the carbohydrate moieties, was evaluated with respect to its ability to interfere with H. pylori mucosal attachment. H. pylori cells were incubated with sulglycotide or human gastric mucin and then examined for their inhibitory capacity of H. pylori attachment to erythrocytes. Titration data revealed that the mucin inhibitory activity was confined to its sulfomucin fraction, the titer of which was found to be 16-fold higher than that of intact mucin. The data with sulglycotide showed that the inhibitory titer of this agent against H. pylori attachment was at least 30-fold higher than that of the sulfated gastric mucin fraction. The results point towards the involvement of sulfomucins in the protection of gastric mucosa from H. pylori colonization and demonstrate that sulglycotide, because of structural similarities, is ideally suited to augment the inherent mucosal defenses against this pathogen. PMID- 8508148 TI - Identification of calcium-activated neutral protease activity and regulation by parathyroid hormone in mouse osteoblastic cells. AB - Calcium-activated neutral protease activity was detected in mouse MC3T3-E1 cell extracts. Inclusion of the cysteine protease inhibitor, E64c, reduced the activity, while pretreatment of intact cells with 10 nM parathyroid hormone for 90 minutes increased it. The presence of calpains in solubilized cells was confirmed by Western blotting using an antibody specific for the 80 K catalytic subunit. These results, combined with the observation that preincubation with a membrane-permeable cysteine protease inhibitor ablates 50% of the PTH-induced osteoblastic retraction, suggest that calpain-catalyzed hydrolysis of regulatory enzymes or structural proteins plays a role in mediating its short-term effects in bone. PMID- 8508149 TI - Tetanus--Ontario. PMID- 8508150 TI - Tetanus--Alberta, 1991 and 1992. PMID- 8508151 TI - Second European workshop on drug information. Brighton, United Kingdom, 6-8 May 1993. Abstracts. PMID- 8508152 TI - Clinical pharmacological meeting. Utrecht, The Netherlands, 2 April 1993. Abstracts. PMID- 8508153 TI - Predictors of antidepressant response. AB - The development of new pharmacological agents has dramatically improved the treatment of major depressive disorders. But the question of whether there are reliable predictors of response to a particular agent or class of agent remains to be answered completely. The author provides an overview of current understanding of antidepressant response prediction in terms of three sources of variance: clinical variables, biological variables, and pharmacological response. He also notes evidence of the effectiveness of two nonpharmacological treatments, sleep deprivation therapy and light therapy. PMID- 8508154 TI - Whose body is it anyway? Understanding and treating psychosomatic aspects of eating disorders. AB - Eating disorders can be understood as psychosomatic illnesses in which the body is pitted against the psyche. The author explores a variety of theoretical principles that aid understanding of the eating disorders and inform treatment interventions. She explains various therapeutic interventions and discusses countertransference difficulties that may hinder work with eating disorder patients. A theoretical understanding of the nature of psychosomatic dissociation in these patients enables treaters to understand why treatment often takes a very long time and is met with strong resistance even as the patient clamors for help. PMID- 8508155 TI - Trauma and dissociation. AB - The stress associated with experiencing or witnessing physical trauma can cause abrupt and marked alterations in mental state, including anxiety and transient dissociative symptoms. Intense manifestations of this pattern of response to trauma are described in a new diagnostic category proposed for DSM-IV: acute stress disorder. Severe dissociative symptoms may predict subsequent posttraumatic stress disorder. Persons who experience a series of traumatic events may be especially vulnerable to a variety of dissociative states, including amnesia, fugue, depersonalization, and multiple personality disorder. Treatment for these symptoms emphasizes strengthening supportive interpersonal relationships and developing insight that reduces psychological pain by integrating the trauma into a meaningful, less self-blaming perspective. PMID- 8508156 TI - The doctor-patient relationship and medical malpractice litigation. AB - Little empirical data support the allegation that a good doctor-patient relationship prevents litigation. However, physicians--including psychiatrists- should be alert to critical events that generate anxiety in both doctor and patient and thus disrupt the equilibrium of their relationship. The author discusses reactions in doctor and patient that may lead to further disequilibrium, the outcome of which may be litigation. PMID- 8508157 TI - Management of the aggressive and dangerous patient. AB - Violence is the ultimate maladaptive coping behavior manifested by a small but significant number of psychiatric patients. The management of the aggressive and dangerous patient depends on recognition of predisposing developmental experiences, cognitive and behavioral factors, and situational circumstances that potentiate a violent outburst. The author presents management guidelines, which stem from an understanding of the paranoid process, respect for the limited coping skills of the individual, and appropriate use of verbal, physical, and chemical interventions. PMID- 8508158 TI - Varieties of the catastrophic reaction to brain injury: a self psychology perspective. AB - Patients with traumatic brain injury sometimes manifest varieties of what Goldstein (1952) called the "catastrophic reaction." Recognizing the particular form of catastrophic reaction is important both to determine proper behavioral management and to help patients accept the effects of the brain injury. Applying Kohutian theory and self psychology constructs, the authors present several case studies to show how the patients shared the same underlying experience of shame and anxiety over their injury-related impairments. These patients participated in an outpatient, milieu-oriented rehabilitation program intended to increase their independence at home and to facilitate their return to productive work. The rehabilitation therapist's role was to help patients move from a state of being unable to accept their deficits to one of setting and pursuing attainable goals. The authors discuss ways of managing these catastrophic reactions. PMID- 8508160 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 8508159 TI - An atypical eating disorder in a 2-year-old female. AB - The case of a 21-month-old girl with an atypical eating disorder helps illustrate the impact that a serious illness and subsequent hospitalization may have on a young child's psychosexual development. The consultant emphasizes how assessing the interaction between the child's development and her environment can help treaters understand the child's self-experience during the hospitalization that led her to develop an eating disorder. Participants in the presentation discuss implications for intervention in a pediatric-liaison setting. PMID- 8508161 TI - The isolation and partial characterization of a Babesia sp. from desert bighorn sheep (Ovis canadensis nelsoni). AB - A novel Babesia parasite of desert bighorn sheep was isolated. Its taxonomic description, host range, pathogenicity and antigenic relatedness were investigated. The parasite was infective for black-tailed and white-tailed deer, but with host-specific differences compared to that of bighorn sheep. A splenectomized calf and domestic sheep were refractory to infection. A comparative immunofluorescence assay detected antigens cross-reactive with Babesia odocoilei, B. divergens, B. equi and B. caballi, but not with B. bovis or B. bigemina. Babesia odocoilei was also infective for bighorn sheep, allowing comparison by a cross-challenge experiment, the results of which supported the conclusion that this parasite was not B. odocoilei. However, the bighorn sheep Babesia cannot currently be distinguished from B. capreoli described from roe deer in northern Germany. Data indicate that, while this parasite may not present a problem for domestic animals, it may cause disease in bighorn sheep and deer populations. PMID- 8508162 TI - Quassinoids exhibit greater selectivity against Plasmodium falciparum than against Entamoeba histolytica, Giardia intestinalis or Toxoplasma gondii in vitro. AB - The in vitro activities of a series of quassinoids against Plasmodium falciparum, Entamoeba histolytica, Giardia intestinalis and Toxoplasma gondii have been compared with their in vitro cytotoxic effects against KB cells (human epidermoid carcinoma of the nasopharynx). All of the compounds tested were more toxic to KB cells than to G. intestinalis, but four (ailanthinone, bruceine D, brusatol and glaucarubinone) were slightly less toxic to KB cells than to E. histolytica. Glaucarubinone was similarly more toxic to intracellular T. gondii than to KB cells but ailanthinone was more selective (36 times more toxic to T. gondii than to KB cells). All of the compounds were more toxic to P. falciparum than to KB cells; the most selective quassinoids--glaucarubinone, bruceine D, ailanthinone and brusatol--were found to have toxicity/activity ratios of 285, 76, 48 and 32 respectively. These results suggest that quassinoids have a selective action on P. falciparum. Further studies to elucidate the basis for this are in progress. PMID- 8508163 TI - Oxygen uptake in cysts and trophozoites of Giardia lamblia. AB - Oxygen uptake in cysts and trophozoites of the parasitic protozoan Giardia lamblia was examined. Both showed oxygen uptake activity, but that of cysts was only 10% to 20% that of trophozoites. Oxygen dependence of oxygen uptake in cysts and trophozoites showed oxygen maxima above which oxygen uptake decreased. The oxygen concentration at which the oxygen uptake rate was greatest was higher for trophozoites than for cysts. The effect of various inhibitors on cyst and trophozoite oxygen uptake suggested that flavoproteins and quinones play some role in oxygen uptake. The substrate specificities and the effect of inhibitors on G. lamblia trophozoites were similar to those observed for G. muris. Metronidazole, the drug most commonly used in treatment of giardiasis, inhibited oxygen uptake and motility in trophozoites; however, it had no obvious effect on either oxygen uptake or excystation in cysts. Menadione, a redox cycling naphthaquinone, first stimulated, then completely inhibited, oxygen uptake in cysts and trophozoites; a complete loss of cyst viability and trophozoite motility was also observed. The effect of menadione on G. lamblia may indicate that redox cycling compounds have potential as chemotherapeutic agents for the treatment of giardiasis. PMID- 8508164 TI - Effects of mesoionic xanthine analogs on Trypanosoma musculi development in mice. AB - Two derivatives of the mesoionic thiazolo[3,2-a]pyrimidine-5,7-diones 1 were prepared and examined for in vivo antiprotozoan activity to study structure activity relationships that might lead us to more active derivatives. Mesoionic compounds 1A and 1B were inoculated into Swiss Webster male mice with Trypanosoma musculi infection. The effects were measured by studying parasite populations during the course of patent period (days 9 through 15 post-infection). The injection of 200 micrograms of compound 1A along with 5 x 10(4) trypanosomes affected the level of parasitemia at both the peak and during days 9 to 13 post infection. Experimental animals that received drug 1A prior to and after infection with T. musculi developed significantly lower parasitemia as compared to the control animals at the height of parasite populations (day 11 of observation). The group that received the drug simultaneously with trypanosome infection had significantly lower parasitemias on day 11 and 13 of infection compared to the controls. The injection of 200 micrograms of mesoionic compound 1B along with 5 x 10(4) trypanosomes resulted in lower parasitemic levels in the prior treated and post inoculated groups on days 9 and 13 post-infection. Swiss Webster male mice treated with the test drug, compound 1B, simultaneously with an inoculation of parasites developed significant resistance against infection on days 9 and 11 post-infection. This trend was reversed for the rest of the observation period. PMID- 8508165 TI - In vitro induced anaerobic resistance to metronidazole in Trichomonas vaginalis. AB - Resistance to metronidazole detectable under anaerobic conditions was induced in two Trichomonas vaginalis strains (TV 10-02 and MRP-2) by cultivation at gradually increasing pressure of the drug (1-100 micrograms/ml) for 12 to 21 months. The resistant derivatives reproduced in anaerobic trypticase-yeast extract-maltose medium at 100 micrograms/ml metronidazole and showed very high values of minimal lethal concentration for metronidazole in anaerobic in vitro assays (556-1,600 micrograms/ml at 48-h exposure to the drug). Stepwise selection was necessary to develop the resistance in either strain. Attempts to induce resistance by prolonged maintenance of trichomonads with constant, low or moderate drug concentrations (3-10 micrograms/ml) were unsuccessful. Freshly developed resistance to high concentrations of metronidazole was unstable in absence of drug pressure as well as after cryopreservation. Development of stable resistance required further cultivation at 100 micrograms/ml metronidazole. Unstable substrains did not revert to original susceptibility. They retained a moderate level of resistance, being able to grow at 10 micrograms/ml metronidazole. The strains with fully developed resistance had no activity of the hydrogenosomal enzymes pyruvate: ferredoxin oxidoreductase and hydrogenase and ceased uptake of [14C]-metronidazole. These findings indicate that the pyruvate oxidizing pathway responsible for metronidazole activation was inactivated and metabolism of the drug stopped. PMID- 8508166 TI - Novel structure in the pellicular complex of Plasmodium falciparum gametocytes. AB - Using transmission electron microscopy, transverse dense bands were found to be associated with subpellicular microtubules and inner membranes in Plasmodium falciparum gametocytes. These dense bands may act as supportive structures to maintain the parallel arrangement of the microtubules, and/or to connect them to the inner membranes. PMID- 8508167 TI - Gametogenesis and sporogony of Hepatozoon mocassini (Apicomplexa: Adeleina: Hepatozoidae) in an experimental mosquito host, Aedes aegypti. AB - The sexual life cycle of the hemogregarine Hepatozoon mocassini was studied in Aedes aegypti, an experimental mosquito host, using transmission electron microscopy. Gamonts were observed leaving the host snake erythrocyte as early as 30 min after mosquitoes ingested infected blood, and some gamonts had penetrated the gut epithelial cells by this time. Six hours post-feeding, gamonts were identified within cells of the abdominal fat body. Twenty-four hours post feeding, gamonts were often entrapped within the peritrophic membrane, but were no longer observed within the gut wall. Parasites pairing up in syzygy and undergoing sexual differentiation were observed within fat cells at this time, and by 48 hours post-feeding, well-developed macro- and microgametocytes as well as microgametes were discernible. Developing zygotes observed 3 days post-feeding were enclosed within a parasitophorous vacuole. By day 6, multinucleate oocysts with crystalloid bodies in the cytoplasm were seen. Sporozoites developing within sporocysts appeared by day 12. Seventeen days post-feeding, mature oocysts with sporocysts containing approximately 16 sporozoites were observed upon dissection of mosquitoes. Large crystalloid bodies no longer bound by rough endoplasmic reticulum were located anterior and posterior to the sporozoite nucleus. Free sporozoites were not observed. PMID- 8508168 TI - Disruption of Ca2+ homeostasis in Trypanosoma cruzi by crystal violet. AB - We have demonstrated previously that crystal violet induces a rapid, dose-related collapse of the inner mitochondrial membrane potential of Trypanosoma cruzi epimastigotes. In this work, we show that crystal violet-induced dissipation of the membrane potential was accompanied by an efflux of Ca2+ from the mitochondria. In addition, crystal violet inhibited the ATP-dependent, oligomycin , and antimycin A-insensitive Ca2+ uptake by digitonin-permeabilized epimastigotes. Crystal violet also induced Ca2+ release from the mitochondria and endoplasmic reticulum of digitonin-permeabilized trypomastigotes. Furthermore, crystal violet inhibited Ca2+ uptake and the (Ca(2+)-Mg2+)-ATPase of a highly enriched plasma membrane fraction of epimastigotes, thus indicating an inhibition of other calcium transport mechanisms of the cells. Disruption of Ca2+ homeostasis by crystal violet may be a key process leading to trypanosome cell injury by this drug. PMID- 8508169 TI - Antagonistic action of the bacterium Bacillus licheniformis M-4 toward the amoeba Naegleria fowleri. AB - Free-living amoebae belonging to the species Naegleria fowleri are known to be the etiological agents for a form of fulminant meningoencephalitis that is generally fatal (primary amoebic meningoencephalitis). In a broad bacterial screening from soil and water we have isolated three strains (M-4, D-13 and A-12) belonging to the species Bacillus licheniformis that have remarkable amoebicidal activity against Naegleria sp. and also against different Gram-positive and Gram negative bacteria. Physical-chemical characteristics, partial purification and biological activities of a substance produced by the M-4 strain have been investigated. This substance (m-4) is stable at high temperature (up to 100 degrees C) and extremes of pH (2.5-9.5) and also at -20 degrees C for months. Its production is greatly influenced by oxygenation of the cultures and is probably related to the sporulation process of the bacterium. Scanning electron microscope observations reveal that amoebae are lysed after a few minutes contact with m-4. PMID- 8508170 TI - Evaluation of rhodamine 123 as a probe for monitoring mitochondrial function in Trypanosoma brucei spp. AB - Rhodamine 123, a membrane potential-specific dye, has been evaluated as a probe to monitor the function of the mitochondrion in long slender bloodstream and procyclic trypomastigotes of several Trypanosoma brucei spp. By epifluorescence microscopy, mitochondrial development has been followed in long slender bloodstream and procyclic organisms stained with rhodamine 123. To photograph stained long slender bloodstream forms, it was necessary to develop a method to completely immobilize viable organisms. In both parasite forms, as the cell cycle progressed, the mitochondrion developed from a thread-like structure to a highly branched organelle. A dramatic reorganization occurred preceding cytokinesis to produce two progeny thread-like structures which were partitioned into newly formed daughter cells. The organelle within the long slender trypomastigote was found to stain optimally at 0.3 microgram/ml of rhodamine 123, while the procyclic form required 3.0 micrograms/ml. The results suggest that the plasma membrane potential is higher in the long slender parasite than in the procyclic form. The effects of inhibitors that disrupt mitochondrial function were examined in long slender and procyclic parasites, and some of these agents were shown to affect rhodamine 123 accumulation and retention. In long slender trypomastigotes the trypanosome alternative oxidase does not appear to be coupled to proton pumping, whereas in procyclic organisms the effects of inhibitors indicate that this oxidase may be coupled to a pathway that is branched preceding an antimycin A1-sensitive site. PMID- 8508171 TI - Lipophosphoglycan antigen shedding by Leishmania donovani. AB - The biochemical characterizations of lipophosphoglycans from various Leishmania species reported by other workers may or may not contain several types of lipophosphoglycan molecules. This is the first report in which a specific lipophosphoglycan has been defined by both its antigenic and electrophoretic properties. Furthermore, a purification procedure for this specific lipophosphoglycan is described and some biochemical characterizations are presented. Phospholipase C and the so-called phosphatidylinositol-specific phospholipase C of Bacillus cereus convert the amphipathic form of the lipophosphoglycan antigen to the hydrophilic form. Under equivalent incubation conditions, other phospholipases tested were not effective in conversion of the amphipathic to the hydrophilic form. Since the amphipathic form is present in conditioned media, antigen shedding cannot be explained by phospholipase C digestion of the amphipathic form, which would result in the release of only the hydrophilic form into the medium. Both the pellet and the supernatant fractions of conditioned media contained both forms of the antigen and did not differ in the relative amounts of the two. This observation rules out membrane blebbing as the major mechanism for the release of the amphipathic form. PMID- 8508172 TI - A redescription of Entamoeba histolytica Schaudinn, 1903 (Emended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1925. AB - Explaining the low incidence of invasive disease (10%) in humans infected with Entamoeba histolytica has occupied the attention of generations of both clinical and nonclinical investigators. One possible explanation would be the existence of two morphologically identical species-one an invasive pathogen, the other noninvasive. This was first proposed by Brumpt in 1925, but his explanation was virtually ignored until 1978 when the first of several publications appeared suggesting that E. histolytica did indeed consist of two species. We have reexamined Brumpt's claim in light of recent biochemical, immunological and genetic studies and conclude that the data derived from these investigations provide unequivocal evidence supporting his hypothesis. With this in mind, we redescribe the invasive parasite retaining the name Entamoeba histolytica Schaudinn, 1903 (Emended Walker, 1911), and set it apart from the noninvasive parasite described by Brumpt, Entamoeba dispar Brumpt, 1925. PMID- 8508173 TI - Myosin-like protein (M(r) 175,000) in Gregarina blaberae. AB - A myosin-like protein (M(r) 175,000) was detected in the parasitic protozoan Gregarina blaberae, by both immunofluorescence and immunoblotting of one- and two dimensional electrophoresis gels using anti-myosin antibodies. This protein was present in the trophozoite ghost but not in the cytoplasmic extract, nor in extract from the sexual stage, suggesting a protein-stage-dependent expression. The protein tightly bound to the cortical membranes was insoluble at low ionic strength, or in detergent solutions, but could be extracted from Gregarina ghosts by 6 M urea in high ionic strength solution (0.5 M NaCl) and in the presence of reducing agents (20 mM DTT). The protein was localized by indirect immunofluorescence in the cortex of the epimerite, in the fibrillar disc (the so called septum) separating the proto- and the deutomerite segments, in the contractile ring or sphincter at the top of the protomerite, and as longitudinal lines underlying the G. blaberae epicyte folds. The presence of both actin-like and myosin-like proteins would be consistent with a role in gliding and other cell motility processes of this parasite. PMID- 8508174 TI - The kinetics of fatty acid uptake by Paramecium tetraurelia. AB - The kinetics of radiolabeled fatty acid uptake by the ciliate Paramecium tetraurelia was examined on a homologous series of saturated, straight chain fatty acids of even carbon numbers. Uptake rates increased with chain length from acetate to palmitate. Saturation kinetics was demonstrated for most fatty acids examined, thus ruling out simple diffusion as the major mechanism for fatty acid transport and implicating carrier-mediated, facilitated transport as the major mechanism. Data from most competitive inhibition experiments were too scattered to determine the number of transporter systems present. Cholesterol uptake also exhibited saturation kinetics and hence other sterols, which can satisfy this nutritional requirement, may also be transported by a carrier-mediated mechanism. The uptake of the essential fatty acid oleate was faster than those observed for the saturated acids and could not be explained by only one transport mechanism. Therefore, fatty acid transport also occurs via other kinetically significant routes. PMID- 8508175 TI - Gametocytogenesis of Leucocytozoon smithi. AB - Development of young gametocytes of Leucocytozoon smithi into morphologically mature forms was studied using electron microscopy. Gametocytogenesis began on day seven post inoculation when merozoites, released from ruptured hepatic schizonts, developed into gametocytes within mononuclear phagocytes or leukocytes (monocytes or lymphocytes). No gametocytes were observed in any erythrocytes or polymorphonuclear leukocytes. Two gametocyte forms, round and elongate, were observed. Immature round gametocytes occurred on days 7-10 post inoculation in the deep vasculature of liver, lung and spleen. Mature elongate gametocytes were observed beginning on day 12 post inoculation in both the deep tissue vasculature and peripheral circulation of the turkey host. Growth and elongation of the gametocyte resulted in distortion of the host cell and its nucleus. The host cell nucleus initially was elongated and displaced to one side or indented by the growing parasite. Eventually, the nucleus was laterally compressed or split into two or three fragments. The compressed host cell cytoplasm was displaced longitudinally and stretched over the parasite to form horn-like cytoplasmic extensions from each end. The potential role of microtubules in the elongation of the gametocyte and its host cell, and possibly in the indentation and splitting of the host cell nucleus, is discussed. PMID- 8508176 TI - Density spectral array, evoked potentials, and temperature rhythms in the evaluation and prognosis of the comatose patient. AB - Glasgow Coma Scale (GCS), density spectral array (DSA), EEG, BAEP and circadian temperature rhythm were studied in comatose patients in order to determine level of arousal and appraise the prognostic capability of these combined measures. Subjects were 29 comatose patients in the neurosurgical ICU at the Rambam Medical Center suffering from head trauma, vascular disorders or metastatic growth. Results show that best prognostic capabilities were for DSA, GCS and BAEP, in that order. As a single parameter physiological response to a sound stimulus (increase in EMG, change in EEG frequency and appearance of sharp waves or k complex) was the single best predictor for outcome, with significant response rates for the good, deficit, vegetative and death outcomes at 83%, 57%, 37% and 18%, respectively. Rectal temperature was analysed for 24 h circadian periodicity. Daily acrophases were found to shift forward or backward on the level of about 2-7 h a day with fluctuations about a stable or unstable mean. The absence of 'free-running rhythms' associated with environmental isolation studies might reflect an ability to respond to environmental Zeitgerbers while unconscious. Temperature oscillations as well as 24 h rhythms were found even in the most severely brain-damaged patients, reflecting the resilience of the circadian oscillators in the brain to trauma. PMID- 8508177 TI - AIDS knowledge and risk behaviours among traumatic brain injury survivors with coexisting substance abuse. AB - An exploratory needs assessment for AIDS education and prevention was conducted at a traumatic brain injury (TBI) rehabilitation facility among 29 clients that also experience coexisting substance abuse disorders. The results suggest that the surveyed clients possessed a moderate level of information about AIDS. Their knowledge level was variable with a major source of misinformation surrounding the use of condoms. The sample members' knowledge was not related to the type or severity of substance abuse, nor was it associated with safer sexual practices. The present results are compared to earlier findings that used an identical survey with a dual disordered population of psychiatrically impaired substance abusers. The results should help in developing an AIDS education and prevention programme for clients with the dual diagnosis of TBI and substance abuse. Clients need up-to-date information that can be comprehended and used. Education will need to be coupled with approaches that present both behavioural and attitudinal change strategies that are best suited to these clients. PMID- 8508178 TI - The scaling of the Katz Adjustment Scale in a traumatic brain injury rehabilitation sample. AB - Based on the KAS-R1 ratings completed by 88 relatives of clients who had enrolled in a post-acute rehabilitation programme, the 10 component groups discerned by Fabiano and Goran [1] were submitted to a classical analysis of tests. Seventy nine items were found to contribute to the internal consistency of their respective component groups, resulting in alpha values ranging from 0.75 to 0.93 for the component groups. Intercorrelations between components suggested that while some degree of overlap existed between groups, they represented discrete categories of neurobehavioural functioning. Second-order components, as determined by principal-component analysis, discern two significant component groups. These two components correlated moderately, yielding a value of 0.49. The findings indicate that the revised KAS-R1 exhibits considerable potential for clinical utility. Further research is needed to investigate the validity of this instrument in accurately depicting behavioural manifestations of those who have incurred traumatic brain injury. PMID- 8508179 TI - The effects of parental traumatic brain injury on the behaviour of parents and children. AB - Little is known about the effects of a parent's brain injury and subsequent disabilities on the children in the family. This study examines 24 families in which one parent is brain injured. In each family the children were born before the parent's injury and still lived at home at the time of interview. Reports of the uninjured parent indicate that most of the children experienced some degree of negative behavioural change after the parent's injury. In 10 of the families, significant and problematic changes occurred. Types of problems included poor relationship with the injured parent, acting-out behaviour and emotional problems. Correlates of poor outcomes for the children were: (1) injured parent's gender, (2) compromised parenting performance of the injured parent, (3) compromised parenting performance of the uninjured parent and (4) depression in the uninjured parent. This study points to the importance of recognizing traumatic brain injury as a major family stressor. PMID- 8508180 TI - The interplay between emotional and cognitive recovery after closed head injury. AB - This study examined 59 patients who had suffered closed head injuries with respect to their MMPI scores and Category Test scores as assessed shortly post injury and on subsequent assessment. The number of MMPI scales elevated above t = 70 on the first assessment was negatively correlated with the magnitude of improvement made on the Category Test. Multiple regression analyses showed that the extent of cognitive deficit, as indicated by the Category Test, could be predicted from the degree of psychopathology, with MMPI scales 2 (depression), 7 (psychasthenia) and 8 (schizophrenia) being highly predictive of Category Test performance. These results suggest that patients with better psychological functioning perform at a higher level and make a greater post-traumatic recovery on neurocognitive tests. Although we cannot determine if the emotional impairment is due to neuropathology or is reactive in nature, there are clear implications for rehabilitation. PMID- 8508181 TI - Centripetal and centrifugal family life cycle factors in long-term outcome following traumatic brain injury. AB - The family life cycle model categorizes stresses on family systems in terms of their source and their effects on family members. Centripetal forces bring members together while centrifugal forces lead to loosened intrafamilial ties. This study examined the association of normative, developmental and centripetal illness-related family forces with patient outcome. Hypothesized centripetal and centrifugal forces acting on 65 families of married male TBI patients were used as independent variables in stepwise multiple regressions with criterion measures of quality of life outcome used as dependent measures. Centripetal variables included measures of family coping, marital adjustment, and number of years married. Centrifugal variables included number of children, age of oldest child, and amount of perceived financial strain. Regression equations obtained had multiple R's ranging from 0.623 to 0.407 (p values < 0.017). Results suggest that families normatively dealing with the developmental stage of the family with young children may face unique challenges when a husband sustains a TBI, particularly when financial strain exists. Stages in family development involving conflict between centripetal and centrifugal forces may be most problematic for families to resolve, and potentially the most effective periods for intervention. PMID- 8508182 TI - Clinical management of a man with complex partial seizures and a severe head injury. AB - A case history of a man with complex partial seizures resulting from a severe head injury following a road traffic accident is presented. Details of medical intervention and neuropsychological assessment are also presented and discussed, highlighting the difficulties of balancing therapeutic doses of anticonvulsant medication with cognitive functioning adequate to maintain expected quality of life. An interesting finding revealed that the patient's blood-sodium levels increased rather than decreased with rising doses of anticonvulsant medication. PMID- 8508183 TI - Post-traumatic seizures: a critical review. AB - Post-traumatic seizures are a well-recognized complication of head injury; however, the issue of seizure risk assessment remains controversial. The authors present a critical review of the literature pertaining to post-traumatic seizures, with particular emphasis on current concepts of definitions, incidence and risk factors. Different methods of risk assessment are reviewed and the possibility of utilizing functional imaging techniques for seizure risk assessment is also explored. PMID- 8508184 TI - Awareness and goal setting with the traumatically brain injured. AB - One of the most disabling effects of traumatic brain injury is limited awareness of cognitive, emotional and interpersonal functioning. For this reason it is often difficult for a traumatically brain-injured person to form realistic goals and appreciate the need for rehabilitation. A goal-setting process is outlined in which therapists play a supportive but nondirective role and goals are developed which incorporate information in self-awareness. The aim of this approach is to create goals which are realistic and increase the likelihood of maintenance following treatment. Specific strategies to incorporate patient awareness during goal setting are discussed. PMID- 8508185 TI - Arachidonic acid and prostaglandin E2 in Malpighian tubules of female yellow fever mosquitoes. AB - The fatty acid compositions of Malpighian tubules from adult females of the mosquito Aedes aegypti were determined for total lipids, phospholipids, triacylglycerols and three phospholipid fractions, namely phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol/phosphatidylserine (PI/PS). The prostaglandin precursor arachidonic acid (20:4n-6) occurred in total lipids and phospholipids, but not triacylglycerols. Within phospholipids, nearly all of the 20:4n-6 was detected in PC, with only traces in PE, and none was detected in PI/PS. Isolated Malpighian tubules incorporated exogenous radioactive 20:4n-6 into tissue phospholipids and diacylglycerols, with most of the radioactivity recovered in diacylglycerol. These data indicate selective incorporation of 20:4n-6 into tissue lipids. PGE2 was detected in Malpighian tubule whole mounts by immunohistochemical staining. These findings support the idea that prostaglandins are physiologically active in mosquito Malpighian tubules. PMID- 8508186 TI - The cDNA and deduced protein sequence of house fly NADPH-cytochrome P450 reductase. AB - Antisera to purified house fly NADPH-cytochrome P450 reductase were used to select cDNA clones from an expression library of abdomens of phenobarbital treated house flies. A partial cDNA of 1841 bp containing a TAG termination codon, a consensus polyadenylation site and 269 bp of 3' untranslated sequence was obtained. Sequencing of a genomic clone coupled with mRNA sequencing yielded the complete coding sequence including the starting ATG. The resulting open reading frame of 2013 nucleotides codes for a protein of 671 residues. The native reductase apoprotein has a molecular weight of 76,366 and the deduced molecular weight of the holoenzyme (i.e. with 1 mol of FAD and FMN) is 77,608. The sequence of the house fly P450 reductase protein is highly similar to that of rabbit liver, the overall amino acid positional identity is 54.5% and the overall identity among eukaryotic P450 reductases is about 25%. The P450 reductase gene of 19-23 kb was located on chromosome III, as shown by comparison of RFLP patterns of the P450 reductase gene in two house fly strains and their hybrids. PMID- 8508187 TI - Odorant binding proteins of Heliothis virescens. AB - cDNA clones coding for three different binding proteins were isolated from an antennal library of Heliothis virescens. The deduced amino acid sequences showed only moderate homology to each other but shared several common structural features. Based on a comparison with the predicted primary structures of antennal binding proteins from different moth species, one of the clones (Hel-1) was found to encode a pheromone binding protein, whereas the two others (Hel-10 and -11) encode general odorant binding proteins. PMID- 8508188 TI - cDNA cloning and expression of Rhodnius prolixus vitellogenin. AB - It was shown that Rhodnius prolixus vitellogenin (Vg) is synthesized as precursors of 205 and 190 kDa. Each Vg subunit is antigenically related to a domain in the precursor molecules. Since Vg has been previously detected in R. prolixus male adults, protein synthesis by fat bodies from 5th instar male nymphs was investigated and no Vg synthesis could be detected. Also, a 6.1 Kb RNA is present in female adults but not in 5th instar male nymphs. Therefore, cDNAs from female adult and 5th instar male fat bodies were used for differential screening of a female fat body cDNA library leading to the isolation of several female specific clones. All the clones hybridizing to the female specific 6.1 Kb RNA species were identical. We also describe the construction of new expression vectors, pGex-A and pGex-B, derived from the previously described plasmid pGex 1N. The new vectors, together with pGex-3X, comprise a set of expression plasmids with cloning sites in all three possible reading frames that give a fusion polypeptide with the glutathione S-transferase. This carrier protein can be cleaved by digestion with factor Xa in all three plasmids; one of the Vg cDNA clones was subcloned in pGex-A. Antibodies affinity purified from the fusion protein Vg/glutathione S-transferase recognized both large Vg subunits, suggesting an antigenic relationship between them. Furthermore, the small Vg subunits were not recognized, indicating that they may be localized at the N terminal region of Vg precursors. PMID- 8508189 TI - Sulphate conjugation of serotonin and N-acetylserotonin in the mosquito, Aedes togoi. AB - The sulphate conjugation of serotonin and N-acetylserotonin (NAS) was studied in the mosquito, Aedes togoi, using a high-pressure liquid chromatography radioisotopic procedure. This involved the transfer of the sulphate group from 3' phosphoadenosine-5'-phosphosulphate (PAP35S) to serotonin or NAS by phenolsulphotransferase (PST). NAS, the acetylated product, is less polar than serotonin but it is a better substrate of PST. Its removal would conceivably be facilitated by sulphate conjugation which renders it more water-soluble. This sequential two-step reaction, comprising N-acetylation of serotonin and sulphate conjugation of the acetylated product (NAS) was also demonstrated in vitro. The developmental profile of PST activity using NAS as substrate showed that peak activity occurred at pupation and increased progressively for a few days after emergence of the adult. Based on the selective inhibition of the "P" form of PST by 2,6-dichloro-4-nitrophenol (DCNP), the sulphate conjugation of NAS appeared to be catalysed by the "M" form of PST. PMID- 8508190 TI - Activation of prophenoloxidase with 2-propanol and other organic compounds in Drosophila melanogaster. AB - Activation with 2-propanol and other organic compounds of prophenoloxidase purified from pupae of Drosophila melanogaster was analyzed. A1, one of the two isozymes of the prophenoloxidase, could be activated with both an endogenous activating system and artificial organic compounds including alcohols. A1 was activated within 2 min after addition of 2-propanol. The phenoloxidase activity of A1, which had been activated with 2-propanol, decreased gradually by lowering the concentration of 2-propanol taking c 60 min to attain a low level, and the activity could be re-elevated at the re-introduction of 2-propanol. Thus the reversibility of the activation of A1 in response to the change of the concentration of 2-propanol in the activating mixture could be observed. Optimum concentration of 2-propanol for the rate of activation was 50%, optimum temperature was 30 degrees C and optimum pH was 7.5. The final level of the phenoloxidase activity, which had been activated with 2-propanol, was higher than that activated with the endogenous activating system. The activated state of A1 showed properties of a tyrosinase-type phenoloxidase. The results suggested that the activation of A1 with 2-propanol is caused by the reversible conformational change of the prophenoloxidase molecule. PMID- 8508191 TI - The effect of carbohydrate ingestion on performance during a 30-km race. AB - Seven experienced endurance runners completed a 30-km road race on two occasions separated by 10 days. On each occasion the subjects consumed 250 ml of either a 5% carbohydrate (CHO) solution or nonflavored tap water (W) immediately prior to the start of the race, and 150 ml of the assigned fluid every 5 km thereafter. Performance time for the CHO trial was faster compared with the time recorded for the W trial (128.3 +/- 19.9 min vs. 131.2 +/- 18.7 min [p < 0.01] respectively). Running speed was maintained throughout the race in the CHO trial, whereas a decrease in the running speed occurred after 25 km (p < 0.05) in the W trial. No difference was found between the two trials in blood glucose concentration, plasma electrolyte concentrations, body weight loss, change in plasma volume, and rating of perceived exertion. Blood lactate concentration was higher at 25 km during the CHO trial compared with the W trial (p < 0.01), but plasma FFA and glycerol concentrations were lower at 30 km during the CHO trial than during the W trial (p < 0.05). In conclusion, this study shows that performance time for a 30-km road race is improved after ingesting a 5% CHO solution. PMID- 8508192 TI - The effect of boron supplementation on lean body mass, plasma testosterone levels, and strength in male bodybuilders. AB - The effect of boron supplementation was investigated in 19 male bodybuilders ages 20-27 years. Ten were given a 2.5-mg boron supplement while 9 were given a placebo every day for 7 weeks. Plasma total and free testosterone, plasma boron, lean body mass, and strength measurements were determined on Days 1 and 49 of the study. Plasma boron values were significantly (p < 0.05) different as the experimental group increased from (+/- SD) 20.1 +/- 7.7 ppb pretest to 32.6 +/- 27.6 ppb posttest, while the control group mean decreased from 15.1 +/- 14.4 ppb pretest to 6.3 +/- 5.5 ppb posttest. Analysis of variance indicated no significant effect of boron supplementation on any of the dependent variables. Both groups demonstrated significant increases in total testosterone, lean body mass, 1-RM squat, and 1-RM bench press. The findings suggest that 7 weeks of bodybuilding can increase total testosterone, lean body mass, and strength in lesser trained bodybuilders, and that boron supplementation had no effect on these measures. PMID- 8508193 TI - Carbohydrate intake and recovery from prolonged exercise. AB - The influence of increased carbohydrate intake on endurance capacity was investigated following a bout of prolonged exercise and 22.5 hrs of recovery. Sixteen male subjects were divided into two matched groups, which were then randomly assigned to either a control (C) or a carbohydrate (CHO) condition. Both groups ran at 70% VO2max on a level treadmill for 90 min or until volitional fatigue, whichever came first (T1), and 22.5 hours later they ran at the same % VO2max for as long as possible to assess endurance capacity (T2). During the recovery, the carbohydrate intake of the CHO group was increased from 5.8 (+/- 0.5) to 8.8 (+/- 0.1) g kg-1 BW. This was achieved by supplementing their normal diet with a 16.5% glucose polymer solution. An isocaloric diet was prescribed for the C group, in which additional energy was provided in the form of fat and protein. Run times over T1 did not differ between the groups. However, over T2 the run time of the C group was reduced by 15.57 min (p < 0.05), whereas those in the CHO group were able to match their T1 performance. Blood glucose remained stable throughout T1 and T2 in both groups. In contrast, blood lactate, plasma FFA, glycerol, ammonia, and urea increased. Thus, a high carbohydrate diet restored endurance capacity within 22.5 hrs whereas an isocaloric diet without additional carbohydrate did not. PMID- 8508194 TI - Lack of association between indices of vitamin B1, B2, and B6 status and exercise induced blood lactate in young adults. AB - By means of a 5-week vitamin B-complex supplementation, associations between indices of vitamin B1, B2, and B6 status (activation coefficients [AC] for erythrocyte transketolase, glutathione reductase, and aspartate aminotransferase) and exercise-induced blood lactate concentration were studied. Subjects, 42 physically active college students (18-32 yrs), were randomized into vitamin (n = 22) and placebo (n = 20) groups. Before the supplementation there were no differences in ACs or basal enzyme activities between the groups. The ACs were relatively high, suggesting marginal vitamin status. In the vitamin group, all three ACs were lower (p < 0.0001) after supplementation: transketolase decreased from 1.16 (1.14-1.18) (mean and 95% confidence interval) to 1.08 (1.06-1.10); glutathione reductase decreased from 1.33 (1.28-1.39) to 1.14 (1.11-1.17); and aspartate aminotransferase decreased from 2.04 (1.94-2.14) to 1.73 (1.67-1.80). No changes were found after placebo. Despite improved indices of vitamin status, supplementation did not affect exercise-induced blood lactate concentration. Hence no association was found between ACs and blood lactate. It seems that marginally high ACs do not necessarily predict altered lactate metabolism. PMID- 8508195 TI - Effects of carbonated and noncarbonated beverages at specific intervals during treadmill running in the heat. AB - Eight male runners performed four 2-hr treadmill runs at 65% VO2max in the heat (35 degrees C, 15-20% RH). A different beverage was offered each trial and subjects drank ad libitum for 2 min every 20 min. The beverages were, 6% carbohydrate (CHO) solution (NC 6), 6% carbonated-CHO solution (C 6), 10% CHO solution (NC 10), and 10% carbonated-CHO solution (C 10). NC 6 and C 6 contained 4% sucrose and 2% glucose. NC 10 and C 10 contained high fructose corn syrup. Subjects drank more NC 6 than C 6. Fluid consumption was not different among other trials. During all trials, volume consumed and % delta PV declined while heart rate and rectal temperature increased (p < 0.05). No significant differences occurred between beverages for these variables. Percent body weight lost was greater (p < 0.05) for the C 10 trial compared to the NC 6 trial. Neither sweat rate, percent fluid replaced, plasma [Na+], [K+], osmolality, percent of drink volume emptied from the stomach, or glucose concentration differed among trials. Plasma [K+] and osmolality increased (p < 0.05) over time. Ratings of fullness and thirst were not different among beverages, although both perceptions increased (p < 0.05) with time. It is concluded that (a) carbonation decreased the consumption of the 6% CHO beverage; (b) fluid homeostasis and thermo-regulation were unaffected by the solutions ingested; and (c) fluid consumption decreased with time, while ratings of fullness and thirst increased. PMID- 8508196 TI - Resting metabolic rate and thermic effect of a meal in low- and adequate-energy intake male endurance athletes. AB - The resting metabolic rate (RMR) and thermic effect of a meal (TEM) were determined in 13 low-energy intake (LOW) and 11 adequate-energy intake (ADQ) male endurance athletes. The LOW athletes reported eating 1,490 kcal.day-1 less than the ADQ group, while the activity level of both groups was similar. Despite these differences, both groups had a similar fat-free mass (FFM) and had been weight stable for at least 2 years. The RMR was significantly lower (p < 0.05) in the LOW group compared to the values of the ADQ group (1.19 vs. 1.29 kcal.FFM-1.hr-1, respectively); this difference represents a lower resting expenditure of 158 kcal.day-1. No differences were found in TEM between the two groups. These results suggest that a lower RMR is one mechanism that contributes to weight maintenance in a group of low- versus adequate-energy intake male athletes. PMID- 8508197 TI - Responses to moderate and low sodium diets during exercise-heat acclimation. AB - This investigation examined whether low sodium (Na+) (LNA; 68 mEq Na+.d-1) or moderate Na+ (MNA; 137 mEq Na+.d-1) intake allowed humans to maintain health, exercise, and physiologic function during 10 days of prolonged exercise-heat acclimation (HA). Seventeen volunteers, ages 19 to 21, consumed either LNA (n = 8) or MNA (n = 9) during HA (41 degrees C, 21% RH; treadmill walking for 30 min.h 1, 8 h.d-1 at 5.6 km.h-1, 5% grade), which resulted in significantly reduced heart rate, rectal temperature, and urine Na+ for both groups. There were few between-diet differences in any variables measured. Mean plasma volume in LNA expanded significantly less than in MNA by Days 11 and 15, but reached the MNA level on Day 17 (+12.3 vs. +12.4%). The absence of heat illness, the presence of normal physiologic responses, and the total distance walked indicated successful and similar HA with both levels of dietary Na+. PMID- 8508198 TI - Iron status of female runners. AB - This study was designed to observe iron status and prevalence of iron deficient conditions in adult female habitual runners (n = 111) and inactive females of comparable age (n = 65). The runners were significantly lower (p < .05) than the reference group in mean serum ferritin (SF), total iron binding capacity, and red blood cell count, but significantly higher (p < .05) in mean corpuscular hemoglobin. The groups did not differ significantly in hemoglobin concentration, hematocrit, serum iron, percent saturation of transferrin, or red cell protoporphyrin. Chi square analysis indicated that iron depletion (SF < 20 ng.ml 1) was significantly more prevalent (p < .005) in the runners than in the controls. Anemia was extremely rare in both groups. A multiple regression analysis revealed significant negative associations between serum ferritin and coffee/tea intake (p < .001) and running activity (p < .05). These results indicate that habitual runners, as compared with inactive women, are at increased risk for iron deficient states but that full-blown anemia is a rare consequence of this deficient iron status. PMID- 8508199 TI - Practices and recommendations of sports nutritionists. AB - A three-part questionnaire was used to identify professionals in sports nutrition and survey their recommendations on various aspects of sports nutrition. The majority of respondents were women. Over half of the sample reported working in sports nutrition for 6 years or less, and 72% indicated that 40% or less of their job is dedicated to sports nutrition. A portion of the questionnaire assessed the subjects' opinions on various sports nutrition topics. Statements on water and electrolytes generated the most agreement while statements on protein generated the least agreement. There was a positive correlation (p < 0.004) between level of education and whether or not the respondents recommended glycogen loading, and a positive correlation (p < 0.008) between the subjects' use of dietary supplements and the fact that they recommended supplements to the athletes they counseled. The majority of professionals in this study worked with recreational athletes and were more concerned about encouraging a healthy diet than improving athletic performance. PMID- 8508200 TI - [The treatment of metastasized kidney cancer. Current data and perspectives]. AB - Metastatic renal cancer has a poor prognosis because of the limited impact of traditional treatment modalities on this tumour. The few long-term survivals obtained after isolated surgical resection of the primary tumour or its metastases can be attributed to the occasionally unpredictable natural history of this tumour and isolated surgical resection generally does not appear to improve the survival of these patients. Among non-surgical treatments, radiotherapy is purely palliative and hormone therapy has been shown to be ineffective. New therapeutic approaches have been recently developed, suggesting a possible improvement in the prognosis of metastatic renal cancer. A better understanding of the mechanisms of chemoresistance of renal cancer should lead, in the near future, to the use of drugs capable of increasing the efficacy of cytotoxic chemotherapy in this tumour. The results obtained with new forms of immunotherapy open up prospects for combined immunosurgical modalities. PMID- 8508201 TI - [Immunotherapy of metastatic kidney cancer]. AB - Interleukin 2 (IL2), like Interferon alpha (IFN), is active in metastatic renal cancer, considered to be a chemoresistant cancer. 20 to 30% of objective responses, including 5 to 10% of complete remissions are reported with various protocols of IL2 administration. The considerable toxicity is now well controlled, allowing treatments to be administered in standard wards or even on an outpatient basis by subcutaneous injection. IFN, generally given as long-term treatment, achieved average response rates of between 15 and 20%. Although IL2 and IFN have been granted Product Marketing Authorization in France, the modalities of optimal administration, the place of the combination of IL2 Interferon alpha and the factors predictive of response to treatment still remain unclear. PMID- 8508202 TI - [Celioscopic lymphatic excision and perineal radical prostatectomy: a strategy for the treatment of prostatic cancer]. AB - Radical perineal prostatectomy despite its many advantages over the past decade had decreased in popularity compared with the retropubic approach and was limited to a few specific indications. The primary reason for this trend was in the ability to first evaluate pelvic lymph node metastases by frozen section using only one retropubic incision. Recently our institution has developed an alternative method which combines laparoscopic lymph node dissection (LLND) with radical perineal prostatectomies (RPP). From January 1990 to January 1992, 30 patients with a mean age of 64 were identified as having clinical stage B prostatic carcinoma. From this population a total of 36 procedures were performed by the senior author. 9 patients underwent LLND alone (group 1), 13 patients underwent RPP alone (group 2) and 14 patients underwent combination LLND and RPP (group 3). The mean EBL for groups 1, 2 and 3 were 1.2, 5 and 5.6 days respectively. Number of transfusions for patients requiring blood in groups 2 and 3 were 1.2 units and 1.5 units respectively. There were no significant differences in post-operative stay, post-operative complications, day tolerating diet or days of analgesia despite the difference in operating room and anesthesia time: group 2 (2:25) and group 3 (5:29). All levels of PSA in groups 2 and 3 remain trace at 1, 3, 6 and 12 months post operatively except for one patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508203 TI - [Idiopathic vaginal hydrocele. Treatment using a sclerosing injection of minocycline]. AB - The authors report a series of 31 hydroceles (26 patients) treated by drainage followed by sclerosing injection of minocycline hydrochloride. The pain usually experienced with this injection required the use of general anaesthesia in 38.70% of cases and local-regional anaesthesia in 41.94% of cases. The patients were able to return to work on the day after the procedure, but after 6 months, only 51.61% of them were free of recurrence of the effusion. Patients must therefore be warned about the inconstant results of this technique. PMID- 8508204 TI - [Hydatid cyst of the kidney (apropos of 45 cases)]. AB - Based on a series of 45 cases of renal hydatid cysts, the authors present a general review of the multiple aspects of this rare disease. The mean age at the time of diagnosis is 30 years with a slight female predominance. Renal hydatid cyst often has a suggestive clinical presentation (flank mass in 84% of cases, pain in 73% of cases) and sometimes a specific presentation (hydatiduria in 29% of cases). The authors emphasise the value of laboratory tests, bearing in mind that serology is positive in about one half of cases (57%) and prefer ultrasonography and computed tomography to arteriography for the diagnosis of renal hydatid cyst. Surgical treatment is now well defined. A lumbar incision is performed in 60% of cases and an anterior incision is used in 40% of cases. Conservative treatment occupies a predominant place (84.5% of cases), as resection of the prominent dome is usually sufficient. Total nephrectomy should only be considered in the case of a completely destroyed kidney (15.5% of cases). The postoperative course is generally uneventful and re-expansion of the renal parenchyma is observed in 78% of cases, indicating the benign nature of this disease. PMID- 8508205 TI - [Urethro-cervico-cystopexy using aponeurotic colposuspension: an original technic in the treatment of stress urinary incontinence. Apropos of 32 long-term reviewed cases]. AB - This is an original technique for the treatment of isolated urinary stress incontinence without associated cystocele, designed to obtain a good result, stable in the long term, which avoids dysuria and phenomena of bladder irritation (frequency, urgency) inherent to suspension cervicopexy. It consists of a Gobell Stoeckel operation, modified at two points: retrocervical dissection exclusively via a retropubic incision and fixation of a band of aponeurosis to the vagina before fixing it to Cooper's ligament to prevent compression of the posterior lip of the bladder neck. Thirty two patients with a mean age of 56 years (range: 41 83 years) were operated by this technique between 1986 and 1991. Sixteen of the 32 patients (50%) had a history of previous pelvic surgery: 14 hysterectomies, 4 cures of urinary stress incontinence, 4 cures of cystocele. Stress incontinence was associated with urgency in 25% of cases. Five patients developed 7 minor early complications: 3 benign parietal complications, 4 cases of transient urinary retention. The mean duration of indwelling catheterisation was 4 days (range: 2-6 days) and the mean length of hospital stay was 8 days (range: 6-20 days). The mean follow-up was 32 months (range: 12-70 months). Perfect continence was achieved in 91% of cases. 69% of patients obtained an excellent result (normal continence, no dysuria, no urgency), 19% obtained a moderate result (normal continence, but slight dysuria and/or urgency) and 12% obtained a poor result (2 cases of urge incontinence, 1 case of late incontinence secondary to a neurological lesion and 1 case of permanent incomplete retention requiring endoscopic section of the strip of aponeurosis). On the basis of these good long term results, the authors propose this technique for the treatment of urinary stress incontinence in postmenopausal and/or previously operated women. PMID- 8508206 TI - [Cancer of the penis: the value of systematic biopsy of the superficial inguinal lymph nodes in clinical N0 stage patients]. AB - From 1985 to 1991, bilateral surgical biopsy of the superomedial group of superficial inguinal lymph nodes, considered to be the first draining nodes, was performed in 24 patients with clinical stage T1-3 N0 M0 squamous cell carcinoma of the penis at the same time as surgical treatment of the primary. This procedure was technically successful in every case, but no lymph node metastases were detected. As bilateral biopsy was negative in these 24 patients, clinical surveillance was implemented: review every 2 months for 2 years and self palpation by the patient. Seven patients (29.1%) developed one or more suspicious ilio-inguinal lymph nodes after a mean interval of 11.85 +/- 8.02 months: 1) In 6 patients, bilateral ilio-inguinal lymph node dissection was then performed, confirming the neoplastic nature of the inguinal node metastases without iliac metastases in 3 of these patients. 2) As the remaining patient presented with unilateral iliac node metastases, proven histologically by surgical biopsy, systemic chemotherapy was introduced prior to ipsilateral inguinal lymph node dissection. This finding questions the theory according to which the sentinel superomedial inguinal node constitutes the first draining node and demonstrates the existence of several pathways of lymphatic drainage towards superficial and deep inguinal nodes. This biopsy, which was always negative in our series, is insufficient to guide our therapeutic approach in clinical N0 patients. The decreased complication rate following inguinal lymph node dissection should certainly encourage us to prefer surgery, particularly superficial inguinal lymph node dissection with preservation of the great saphenous vein. PMID- 8508207 TI - [A priori benign Leydig cell testicular tumor: enucleation or radical orchidectomy?]. AB - The histological sections of 5 patients treated for clinically benign Leydig cell testicular tumour (LCTT) were reviewed according to histological criteria presumptive of malignancy. The absence of any sign of severity was only verified in a single case, as none of the other tumours could be considered to be strictly benign. In the light of these findings, great caution is required in conservative indications, especially as these tumours, when they are malignant, are particularly serious due to the inevitable diagnostic delay and their absence of radio- or chemo-sensitivity. PMID- 8508208 TI - [Percutaneous nephrolithotomy (PCNL): evaluation of 250 PCNL by the same operator]. AB - The author reports his 8-year experience of PCNL in 250 patients between the ages of 8 and 86 years, including 31 staghorn calculi and 52 ureteric stones treated via a descending approach. The other stones were pelvic or caliceal and 4 occurred in a solitary kidney. The technique used and the complications are described in detail. The most serious complication was infection, which was almost fatal in 1 case. Haemorrhage (7 cases) and intestinal perforation (2 right colonic perforations) never required surgical intervention. There were no deaths or nephrectomies. The results were immediately perfect (stone-free) in 77.6% of cases and in 82.8% of cases after spontaneous elimination of stone debris or repeat PCNL. PMID- 8508209 TI - [Autosomal dominant polycystic kidney disease: urologic complications and results of kidney transplantation: 217 patients]. AB - The authors report a retrospective series of 217 cases of autosomal dominant renal polycystic disease collected over a period of 30 years in the urology and nephrology departments of Nantes university hospital. They study the incidence of urological complications, observed in 87 patients (40%), consisting of calculi (15%), infection (22%, with 4 deaths), intracystic haemorrhages (3.5%) and urinary tract compression (2%). The diagnostic and therapeutic methods are presented and discussed. The results of renal transplantation are also analysed: 39 patients were transplanted, 72% retained a functioning kidney with a mean follow-up of 44.9 months (range: 12-108 months) and three patients died as a result of infectious complications. The 1-year and 3-year actuarial transplant survival rate of 92% was similar to that of renal transplantations performed for another form of renal disease. Preparation for renal transplantation remains an essential problem: the two major indications for pre-transplantation nephrectomy were the size of the kidneys and the presence of infection. PMID- 8508211 TI - [Traumatic lesion of the glans penis. Reconstruction using a preputial flap]. AB - The authors report a case of glans trauma with partial avulsion of the foreskin repaired by means of a foreskin pedicle flap. The cosmetic and functional result was very satisfactory with a follow-up of 36 months. PMID- 8508210 TI - [Transverse transcolonic cutaneous ureterostomy after pelvic irradiation]. AB - The late urological sequelae of pelvic radiotherapy for cancer sometimes require cutaneous urinary diversion. The local conditions often exclude the use of direct or transileal ureterostomy. Three cases of cutaneous ureterostomy using the transverse colon are presented. There was no operative mortality. A single ureterocolonic stenosis was observed at 12 months and was treated endoscopically. The choice of the transverse colon was based on its position away from the field of irradiation and, consequently, teh absence of radiation lesions, its blood supply which can be used to form pedicles and the possibility of resecting irradiated ureteric segments allowing anastomoses with the proximal ureters. The results reported in the literature show an operative mortality of 0 to 4% and a low morbidity. This technique can be considered to be a technique of choice for cutaneous urinary diversions in urological complications of pelvic radiotherapy. PMID- 8508212 TI - [The tumorous form of bladder malacoplakia. Apropos of 2 cases]. AB - The authors report two rare cases of neoplastic vesical malakoplakia, one with an enterovesical fistula and the other with extravesical pelvic extension. The symptoms are non-specific and the diagnosis remains histological. Medical treatment, based on the suspected infectious physiopathogenesis of the disease, consists of variable combinations of antibiotics, cholinergics and vitamin C. It must be sufficiently prolonged and conservative in view of its usual efficacy, even in neoplastic forms. PMID- 8508213 TI - [Complications of laparoscopic surgery in urology]. AB - The use of laparoscopy has become commonplace in urology over the past several years and will undoubtedly continue to grow. Although the morbidity and mortality of this minimally invasive technique are relatively low, the risks involved must be taken seriously. A thorough understanding of the potential complications allows one to anticipate these events and therefore reduces their likelihood. This paper will review the mechanisms of laparoscopic surgical complications throughout the entire realm of the laparoscopic case. PMID- 8508214 TI - [Computerization in private urologic practice with multiple practice locations: the use of medical software and a portable microcomputer]. AB - The authors have used a medical programme, Medistory, since June 1990 to computerize a private urological practice. This programme allows personalization of data collection adapted to urology: interview sheets related to the disease, standard report forms, edition of letters, creation of a multi-entry file and entering of accounts. The consultation was always held without a paper support with real-time data acquisition and the accounting was performed at the end of the visit. Letters were printed separately at home, at the end of the day, so as not to delay the patient. A back-up was performed every second day on hard disk. We used a portable Macintosh with 20 mega octets of REM and a 40 mega octet internal hard disk as our practice is based at several sites. This computerisation benefited from the Macintosh interface which facilitated learning and use of the programme. No time loss and no patient discomfort were recorded in comparison with a conventional consultation. The possibility of opening several files at the same time allowed a simple reply to any demands for other information. Two files out of 700 were lost (0.3%) due to an error when saving data. No accounting errors were detected. The use of a medical programme is particularly well adapted to private urological practice with multiple offices. The advantages of a personal computer include the gain of place, rapidity, unlimited storage capacity and the possibility of recovering data with other standard programmes. Medistory, a programme created for general practitioners, is perfectly adapted to this use due to the ease of personalization allowing the creation of interview sheets related to the disease and the edition of reports and various letters. PMID- 8508215 TI - Sustainable urban development and human health: septic tank as a major breeding habitat of mosquito vectors of human diseases in south-eastern Nigeria. AB - Septic tank mosquitoes in Abia State University Okigwe, south-eastern Nigeria were studied using exit traps between November 1988 and April 1989. The results were revealing and striking. Apart from the common septic tank mosquitoes, Culex p. quinquefasciatus, Cu. cinereus and Aedes aegypti, which have been previously commonly found breeding in ammonia and nitrate-rich waters of latrines and septic tanks, the other species, Cu. horridus, Cu. tigripes and Aedes vittatus, have not been commonly reported as colonizing septic tanks in Nigeria. Three out of these six mosquito species observed are vectors of human diseases: Aedes aegypti and Aedes vittatus are vectors of Yellow fever and Cu. p. quinquefasciatus is a potential vector of Bancroftian filariasis and a world-wide vector of various arboviruses. The fact that these mosquito vectors are able to breed in highly polluted waters of septic tanks during the harsh dry months when most surface water bodies are dry is epidemiologically important. The breeding of these mosquito vectors of human diseases around human dwellings indicates an intense man-vector contact creating a high level risk to the crowded urban population. The public health implications of this urbanization/modernization problem and solutions are discussed. PMID- 8508216 TI - [A new system for the quantitative evaluation of the effectiveness of an Eimeria tenella radiovaccine]. AB - The quantitative valuation of efficiency of an Eimeria tenella radiovaccine was performed on the basis of 21 tests under floor-pen conditions and on 34 tests under the conditions of industrial broiler production using the vaccination index, the recycling index and coccidiosis protection index. The immunogenic quality of the vaccine was classified quantitatively by the indices 1 to 4, in which the classes 1 and 2 fulfilled the requirements. Under floor-pen conditions the valuation in the classes 1 and 2 was ascertained on the vaccination index with 76.2%, on the recycling index with 44.4% and on the coccidiosis protection index with 100%. Under the conditions of the industrial mast these values amounted 66.7%, 64.7% and 66.7%. PMID- 8508217 TI - Trichomoniasis amongst students of a higher institution in Nigeria. AB - A total of 2048 urine specimens were examined to assess the infection prevalence and epidemiological factors of T. vaginalis amongst students in a Nigerian higher institution. Five hundred and five students were infected (24.7%). This included 131 (15.6%) males and 374 (31.0%) females. More male than female students were found to be asymptomatic. Infection was significantly higher in females than males and in the second and third than the fourth and fifth decades of life (P < 0.05). Infection increases progressively with increase in the number of sexual partners. The use and neglect of condoms were also assessed. The pH range of the vagina of most infected females was between 5.8-8.2. Clinical symptoms noted among females were local tenderness, vulval pruritus and intermittent burning sensations in addition to profuse vaginal discharges. The public health implication of the findings and some epidemiological factors enhancing the disease transmission are presented. PMID- 8508218 TI - [The development of the cestode fauna in rainbow trout (Oncorhynchus mykiss) in a newly formed surface mine residual water]. AB - Helminthofaunistical studies on rainbow trout, wild fish and zooplankton organisms of a recently emerged rest waters from an open-cast mine have been made continuously in the period from 1980 till 1990. Three years after the beginning of the trout production larval triaenophorosis appeared as the first cestodosis. In the subsequent time changes of the cestode fauna of rainbow trout kept in net cages could already be observed within a few years. Possible causes for the replacement of Eubothrium crassum by Proteocephalus neglectus are discussed. Since 1985 proteocephalosis is the dominating helminthosis in the stock of trout. Changes in the population dynamics of cestodes of the genus Proteocephalus are traced back to a multitude of complexly functioning ecological and anthropogenic regulation mechanisms in all links of the life-cycle. PMID- 8508219 TI - [The distribution and biology of Capillaria garfiai from Sus scrofa]. AB - The infestation extent of wild boars (Sus scrofa) with Capillaria garfiai Gallego & Mas-Coma, 1975 in East-Austria and the localisation of the nematodes in the tongue (n = 159) were examined. The infestation extent (prevalence) was between 66.6 and 90.9 percent. Concerning the location of the parasites in the tongue there was a striking difference between C. garfiai males and females. So, the number of C. garfiai females continuously decreased from the first to the fourth quarter of the tongue, whereas C. garfiai males could be found increasingly in the epithelium of the third quarter. Further, we investigated the biology of C. garfiai and could show, that the development is only involving intermediate hosts, which could be identified as earthworms (Lumbricus terrestris, Allolobophora caliginosa, A. rosea). The morphological characteristics of C. garfiai specimens of wild boars and domestic pigs were compared, but no noticeable differences could be detected. PMID- 8508220 TI - Toxicity of Azadirachta indica to freshwater snails and fish, with reference to the physicochemical factor effect on potency. AB - A preliminary crude screening of plants in Jos Metropolis showed that at a concentration of 100 mg/l-1 the stem bark extract of the Neem plant Azadirachta indica caused a 100 percent mortality when tested against three common snail intermediate host species, Biomphalaria pfeifferi, Bulinus truncatus, and Lymnaea natalensis after 24 hours exposure. Toxicity test with freeze-dried aqueous extract of the plant gave 96 hours LC50 values of 19.00 mg/l-1 (p > 0.05), 10.96 mg/l-1 (p > 0.05) and 15.13 mg/l-1 (p > 0.05) against B. pfeifferi, B. truncatus and L. natalensis, respectively. When a similar test was carried out on fish, Aphyosemon giardneri a 96 hour LC50 of 15.1 mg/l-1 was recorded. Extraction with alcohol, increase in temperature within the optimal range, increase in acidity of aquatic medium and cold storage improved the potency of the extract while boiling and room storage reduced it. PMID- 8508222 TI - Field of dreams. How I put health status goals to work in Iowa. Interview by Kevin Lumsdon. PMID- 8508221 TI - Toxicity of washing soaps to Schistosoma mansoni cercariae and effects of sublethal concentrations on infectivity in mice. AB - 5 brands of washing powders and a brand of local soap made in Nigeria were tested for toxicity to cercariae of the Nigerian strain of S. mansoni. The tests revealed that all washing soaps were super-toxic to cercariae at high concentrations, with soap bars being comparatively less toxic. The detergents killed all cercariae instantly at 250-4000 ppm while soap bars achieved the same effect between 3000-4000 ppm. At lower concentration 25-100 ppm, the detergents required less than 60 min to kill 100% of the cercariae while soap bars required less than 12 h. The 12 hours LC 50 and LC 90 for Omo (detergent) and local soap were determined. Also the effects of sub-lethal concentrations 1.25-10 ppm on the infectivity of cercariae in mice were evaluated. These tests revealed that the treatment suppressed infectivity and that the degree of suppression increased with increase in the sub-lethal concentration, 85.4% at 10 ppm as compared to 42.8% at 1.25 ppm. PMID- 8508223 TI - JCAHO accreditation at the crossroads. PMID- 8508224 TI - Reform ... still waiting. Providers and policy experts peer ahead at Clinton's big plan. PMID- 8508225 TI - Balancing complex choices. Integrating strategic, financial plans will test tomorrow's health networks. AB - Juggling capital needs and resource allocation is a formidable task for any health care executive. But what lies ahead poses an even greater challenge: achieving strategic integration in multiprovider health networks. The complexity of determining how best to allocate financial resources while addressing the competing requests of network members is the foremost reason why experts say that common ownership is critical to the operational and financial success of provider networks. PMID- 8508226 TI - Who'll make decisions? Experts debate makeup and power of a national health care board. PMID- 8508227 TI - Revolution in the wings. EDI expected to change way health care takes care of business. PMID- 8508228 TI - Heart network. A new cardiovascular network plans to offer high-quality, low-cost services nationwide. PMID- 8508229 TI - Continuum of care. On ambulatory care's coattails, prevention gets its due. PMID- 8508230 TI - Quantifying quality: experts wonder what's behind numbers. PMID- 8508231 TI - Fewer nuclear waste sites poses problems for hospitals. PMID- 8508232 TI - Data watch. Home Care: robust growth continues. PMID- 8508233 TI - Congress grapples with Medicare reductions outside reform. PMID- 8508234 TI - The last word. No more "business as usual" for hospitals. PMID- 8508235 TI - Eating disorders. PMID- 8508236 TI - Place of obesity clinics in the NHS. PMID- 8508237 TI - Alzheimer's disease aetiology: amyloid and chromosome 14. PMID- 8508238 TI - Neuromuscular diseases in children. AB - Our understanding of neuromuscular disorders has advanced considerably in recent years with developments in molecular genetic techniques. In some conditions we now know the basic pathological defect and, in many, prenatal diagnosis is now available. This review considers the common clinical problems that confront clinicians. PMID- 8508239 TI - Current concepts in atrial fibrillation. AB - The mechanism of atrial fibrillation has recently become clearer, and is understood in terms of multiple irregular wavelets of excitation. This understanding allows a simple model to be proposed which unites the various aetiologies and treatments of atrial fibrillation. PMID- 8508240 TI - Monitoring the biophysical profile. AB - The fetal biophysical profile assesses fetal wellbeing. It is influenced by both physiological factors, e.g. gestational age and behavioural state, and pathological factors, e.g. asphyxia, infection, cardiovascular disease and neurological problems. PMID- 8508241 TI - Biological aspects of personality disorder. AB - A resurgence of interest in the area of personality disorder has been seen in the past 20 years. Researchers have continued along the biological line of investigation working from diverse theoretical standpoints and using increasingly sophisticated approaches. In this review these aspects are set against the background of current debate in the field and placed in their historical context. PMID- 8508242 TI - Videodisc technology. AB - Videodisc has established a niche in education. The combination of exceptional sound and picture quality with near-instantaneous frame addressability has transformed the medium of interactive video, i.e. the notion of communicating with a video programme. Any good system can be used by the most technophobic, but choosing one is rather less simple. PMID- 8508243 TI - Stab injury to the lumbar spine. PMID- 8508244 TI - Doctors, 'living wills' and the law. PMID- 8508245 TI - Pharmaceutical registration and how to get a drug on the market. AB - In this article we describe how to get a drug onto the market and outline the product development stages. Drug development programmes and regulatory control processes are complex, so only a basic outline will be given. PMID- 8508246 TI - Junior doctors' unhappy hours. PMID- 8508247 TI - West resistant to malaria suffering. PMID- 8508248 TI - Respiratory home care: the importance of multidisciplinary collaboration. PMID- 8508249 TI - The fight to protect children's dental health. PMID- 8508250 TI - Heparin for unstable angina. PMID- 8508251 TI - Should mental hospital closure be delayed? PMID- 8508252 TI - The new deal--can we do it? PMID- 8508253 TI - Reporting deaths to the coroner. PMID- 8508254 TI - Growth hormone therapy--whom to treat? PMID- 8508255 TI - When to operate in chronic aortic valvar regurgitation. AB - Chronic aortic valvar regurgitation is a particular problem with heart disease because symptoms develop insidiously and are too severe when the first opportunity arises for a low risk operation. The disease may run a long benign course, but delayed surgery may result in the failure to halt progression of left ventricular failure. PMID- 8508256 TI - Gastroenterology in the elderly. AB - Elderly patients are admitted acutely to most hospital departments. In medical and surgical departments many of them present with gastroenterological symptoms and diseases. In this review, those situations encountered regularly are highlighted and their management is discussed. PMID- 8508257 TI - Acute oxygen therapy. AB - Tissues require oxygen for survival. Its delivery depends on adequate ventilation, gas exchange and distribution in the circulation. Many causes of hypoxaemia can be corrected by adding oxygen to the inspired air but response is variable and must be measured. PMID- 8508258 TI - Current problems in tuberculosis and its management. AB - The decline in tuberculosis (TB) incidence since 1950 stopped in the late 1980s, but the reasons for this arrest are not yet certain. An HIV/TB interaction, such as that described in the USA, has not yet been convincingly shown. Because of the decreased prevalence and variable distribution of TB cases, clinical awareness of TB has been reduced and its management can be suboptimal. PMID- 8508259 TI - Monitoring uterine activity. AB - Uterine activity may be monitored by methods ranging from gentle palpation of the uterine fundus to the most sophisticated electronic intrauterine pressure monitoring system. The form of monitoring required depends largely on the clinical situation. The relationship between fetal oxygenation and uterine contractions has ensured the continued place of cardiotocographic monitoring. PMID- 8508260 TI - Flosequinan: a new vasodilator for the treatment of heart failure. AB - The incidence and prevalence of congestive heart failure is increasing despite improvements in the management of myocardial infarction and hypertension. This trend is likely to continue as the proportion of elderly in the community increases. A new vasodilator, flosequinan, is currently under investigation and may improve prognosis. PMID- 8508261 TI - Ultrasonography in hepatobiliary and gastrointestinal surgery. AB - The use of ultrasonography has been a relatively recent development in abdominal surgery. It is used in vascular and renal surgery, but some of the more exciting and widely applicable developments in operative ultrasonography have occurred in hepatic, biliary and pancreatic surgery. PMID- 8508262 TI - Creeping privatization of the NHS. PMID- 8508263 TI - An analysis of modern man. PMID- 8508265 TI - Open heart surgery in patients on renal replacement therapy. PMID- 8508264 TI - Amiodarone in the elderly. PMID- 8508266 TI - The acute-phase response in relation to radiographic progression in early rheumatoid arthritis: a prospective study during the first three years of the disease. AB - Studies on the relationship between acute-phase protein (APP) production, clinical disease activity and progression of radiological damage in RA have been hampered by three factors: patients are studied at different stages of the disease; APP levels are taken incidentally rather than serially; and inter individual differences in the relationship between the extent of the acute-phase reaction and the progression of radiological damage are not accounted for. A group of 110 newly diagnosed (complaints < 1 year) patients with RA were analysed for a follow-up period of at least three years. Damage was assessed radiologically according to the modified method of Sharp. As radiological progression is a cumulative event, APP production was also calculated by plotting serial CRP levels over time. Overall, a highly significant correlation was found between CRP production and radiological progression; however, a wide variation was observed due to inter-individual differences. The greatest variation was found in the lower range of CRP values, where inter-individual variation could not be accounted for by HLA-DR4, positive RF, sex or age. In conclusion, the prognostic use of serial measurement of APPs for the assessment of radiological progression is limited due to inter-individual variation. Knowledge of the factors underlying these inter-individual differences will increase the applicability of CRP in the prediction of joint damage for individual patients. PMID- 8508267 TI - Rheumatology in the 1990s. A European Rheumatologists in Training (EURORITIS) Workshop. Baden bei Wien, Austria. PMID- 8508268 TI - European rheumatology. Historical perspective. PMID- 8508269 TI - European rheumatology. Training. PMID- 8508270 TI - European rheumatology. Manpower. PMID- 8508271 TI - European medicine. A historical perspective. PMID- 8508272 TI - The European Commission and health care. PMID- 8508273 TI - The implications of 1992 on health care in Europe. PMID- 8508274 TI - Non-steroidal anti-inflammatory drugs. AB - Pre-clinical studies suggest that, whilst NSAIDs have similar anti-inflammatory efficacy, the potential for producing side effects varies widely between members of this class of therapeutic agents. The ways in which NSAIDs produce one of their most serious side effects, gastrointestinal damage, are outlined and consideration is given to ways of minimizing such problems. PMID- 8508275 TI - Osteoporosis. AB - Osteoporosis constitutes a major financial burden for society, which will increase in the near future owing to the ageing of the population. Women are the most common victims of involutional osteoporosis because of post-menopausal bone loss induced by oestrogenic deficit. Men are nevertheless not completely untouched by osteoporosis, however, compared to women, they are under less threat. Every effort should be made to curtail the financial burden on society and to improve the quality of life of sufferers. The first steps should be to increase the calcium intake, the level of exercise and to decrease the risk of falls. A preventive therapy with oestroprogestogens should be instituted at the time of the menopause, provided there is no contraindication. In the absence of fracture data, the modalities of alternative therapies like calcitonin and bisphosphonates are still debated. For people already suffering from fractures, restorative therapy should be considered. Sodium fluoride therapy is able to provoke a decrease in vertebral fracture frequency without compromising cortical bone strength provided elementary rules for its use are respected. Whether bisphosphonates can protect against fractures is still unsettled. Vitamin D has a physiological role, particularly in institutionalized elderly patients deprived of any exposure to the sun. Anabolic steroids are not devoid of side effects, and furthermore, no fracture data are so far available. PMID- 8508276 TI - European medicine. Health care. PMID- 8508277 TI - The Arthritis and Rheumatism Council's national family material repository. PMID- 8508278 TI - Excessive and dysregulated secretion of prolactin in rheumatoid arthritis: immunopathogenetic and therapeutic implications. AB - Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA. PMID- 8508279 TI - Detection of anti-Ro(SSA) antibodies in autoimmune diseases: comparison of five methods. AB - Counterimmunoelectrophoresis (CIE), RNA precipitation, ELISA and immunoblotting against cytoplasmic HeLa cell extract (IB-HeLa) and erythrocyte extract (IB-RBC) were applied to detect anti-Ro(SSA) antibodies in 93 sera selected from patients with various autoimmune diseases [47 were anti-Ro(SSA) positive by CIE]. The RNA precipitation assay, which demonstrated the highest sensitivity was selected as the reference method. CIE was found to be reliable with a specificity of 100% and a sensitivity of 89%. ELISA showed a comparable specificity (95%) but somewhat lower sensitivity (72%). Antibodies to 52 or 60 kDa Ro(SSA) proteins by IB-HeLa demonstrated a high specificity (95 and 97% respectively) but a low overall sensitivity (36 and 17% respectively). Anti-Ro(SSA) antibodies to 52, 54 and 60 kDa erythrocyte proteins by IB-RBC, had a variable overall specificity (95, 97 and 57%) and sensitivity (51, 13 and 34%). The anti-52 kDa antibodies detected by IB-HeLa correlated to those found by IB-RBC (P < 0.001) and occurred predominantly in primary Sjogren's syndrome (P < 0.001, sensitivity: 71 and 77%) as well as in sera with anti-Ro(SSA) and anti-La(SSB) antibodies (P < 0.001). These findings confirm that RNA precipitation assay has the highest sensitivity and specificity for anti-Ro(SSA) antibody detection. However, until a more sensitive ELISA is available, CIE because of its reliability appears to be the method of choice. Finally IB-RBC was found to be more sensitive than IB-HeLa for the detection of anti-Ro52 kDa antibodies. PMID- 8508280 TI - Susceptibility to rheumatoid arthritis is not associated with a single common allele of the type 2 collagen gene (COL2A1) AB - Type 2 collagen is quantitatively the most important constituent of articular cartilage which is the target of progressive destruction in RA. Polymorphism of type 2 collagen could theoretically influence the development of RA either by rendering the cartilage matrix particularly susceptible to autoimmune attack or subsequent degradation. We have investigated the possibility that there is a common allele of type 2 collagen associated with RA by analysing a dimorphism of the corresponding structural gene (COL2A1) in healthy and diseased individuals. We compared haplotype frequencies, defined by the presence or absence of a Hind III restriction site at the COL2A1 locus (encoding type 2 collagen), in 98 patients with classical/definite RA and 158 controls. No differences were seen between the frequencies of individual genotypes in the two groups (maximum chi 2 = 0.7), indicating that susceptibility to this disease does not appear to be determined by the presence of a single common allelic variant at this locus. PMID- 8508281 TI - Patterns of cognitive impairment in patients with systemic lupus erythematosus. AB - This study examined neuropsychological test performance in a representative sample of 70 female patients with SLE. The influence of current or past clinically overt central nervous system involvement, use of corticosteroid medications and overall disease activity were evaluated. The results suggest two distinct patterns of cognitive dysfunction. Impaired delayed recognition memory was associated with past or current nervous system involvement, suggesting the presence of a residual neurologic deficit. Increased disease activity was associated with impaired immediate memory and concentration which may represent transient and diffuse central nervous system effects. Although corticosteroid use was associated with poor word list recall, group differences were not statistically significant when disease activity was considered as a covariate in the analysis. Follow-up studies are required to determine if these abnormalities persist or fluctuate with changes in disease activity and concurrent medications. PMID- 8508282 TI - The 'natural' history of active rheumatoid arthritis over 3-6 months--an analysis of patients enrolled into trials of potential disease-modifying anti-rheumatic drugs, and treated with placebo. AB - The natural history of RA over a period of 6 months is not known, but this is of central importance to the design and interpretation of drug trials of possible DMARDs. We analysed the disease activity of 142 rheumatoid patients who were randomized to receive placebo in five double blind, placebo-controlled trials of possible disease-modifying drugs conducted in a single unit. There was no significant change in ESR, duration of morning stiffness or platelet count over a period of 6 months; the mean change in ESR at 3 months was an increase of 2 mm/h (99% C.I. -3, +7), and only 5% of patients more than halved their ESR over 6 months. There was a small significant fall in articular index over 6 months of placebo treatment. There is no measurable placebo effect on ESR, morning stiffness or platelet count when these are used as measures of disease activity in trials of drug therapy in RA. ESR is an informative, stable measure of disease activity; the duration of morning stiffness may be more useful than the articular index. The use of these results as the basis of a historical cohort to help design future placebo-controlled trials, and to interpret uncontrolled trials of putative anti-rheumatic drugs is discussed. PMID- 8508283 TI - Ranitidine in the treatment of gastric and duodenal ulcers associated with non steroidal anti-inflammatory drugs. AB - To assess the effect of 4 weeks' therapy with ranitidine 150 mg twice daily on the healing of symptomatic NSAID-associated gastric and duodenal ulcers, 149 arthritic patients were randomly allocated to one of three treatment groups: ranitidine with NSAID continued, ranitidine with NSAID discontinued, and placebo with NSAID discontinued. The healing frequency in patients with gastric ulceration was 67, 68 and 47%, and in those with duodenal ulceration 61, 81 and 42%, respectively. Only the difference between the duodenal ulcer healing rates for ranitidine with NSAID discontinued and placebo was statistically significant (P = 0.02). Healing rates were uninfluenced by gender, age, smoking habits, alcohol consumption, ulcer frequency or size, arthritic disease, or participating country. PMID- 8508284 TI - Pathology of skeletal muscle in fibromyalgia: a histo-immuno-chemical and ultrastructural study. AB - The value of muscle biopsy in fibromyalgia is still questioned. In this study we obtained 50 quadriceps biopsies from 20 patients and compared them blindly to 10 biopsies from five normal controls. Using light microscopy, histochemical and immunoenzymatic methods we found no definite evidence of muscle disease. Nevertheless, we subjected biopsies from nine of the patients and five other controls for further ultrastructural evaluations and demonstrated pathologic findings e.g. empty sleeves of basement membrane, many lipofuschin bodies and other degenerative changes. We conclude that ultrastructural evaluation cannot yet be used for diagnostic purposes, but the negative findings with light microscopy, including histochemical and immunoenzymatic techniques, might be of importance in evaluating difficult cases. PMID- 8508285 TI - Patients' beliefs about their lack of pain control in primary fibromyalgia syndrome. AB - This study had two aims, first, to determine the expectancies of control over pain experience ('pain locus of control') of patients with primary fibromyalgia syndrome (PFS) and to compare them with other chronic rheumatic diseases. Second, to analyse the relationships between health status and locus of control. We applied the Multidimensional Health Locus of Control-Pain and the Arthritis Impact Measurement Scales (AIMS), by interviewing 137 out patients (32 PFS, 32 RA, 20 SLE, 22 AS and 31 OA). Data were analysed by ANOVA and partial correlation tests. PFS patients believed that their symptoms depended on uncontrollable events and that they could not influence their disease by themselves. PFS patients were the most disabled on the 'Affect' (P < or = 0.001) and 'Symptom' factors (P < or = 0.01). In the PFS group, patients who showed a 'Fate' locus of control orientation reported more disability on 'Affect' and 'Social Interaction' AIMS factors. PMID- 8508286 TI - Measurement of the range and coupled movements observed in the lumbar spine. AB - The aim of this study was to set up a data base, using the Polhemus Navigation Sciences 3Space Isotrak system, of the range and coupled movements expected to be seen in the lumbar spine of people not experiencing spinal problems. Measurements were taken from groups of volunteers who had not previously experienced any form of serious back pain and who were not suffering from any pathology known to affect the spine. The 'normal' group was split into sections determined by age an dsex. Age was split into five categories, those aged 20-29 years, 30-39 years, 40 49 years, 50-59 years and 60-69 years. Range of motion was seen to be affected by both the age and sex of subjects. Lateral bend and axial rotation, flexion and lateral bend and flexion and axial rotation were all strongly coupled. The younger age groups tested exhibited a greater degree of coupled movement than the older groups. PMID- 8508287 TI - The effect of exercise on ankylosing spondylitis--a preliminary study. AB - The Polhemus Navigation Sciences 3Space Isotrak system was used to measure the range of lumbar spinal motion of 57 patients with ankylosing spondylitis. Forty three of these attended voluntary exercise sessions for an average of one and a half hours per week while 14 did not participate in any formal exercise groups. Exercising patients fell into two groups: those attending moderate and those attending vigorous exercise sessions. Results for exercising patients obtained immediately pre- and post- a single exercise session showed a small but significant increase in extension for the vigorous exercise group but no significant changes in any other movement for either of the groups. In a group of 44 patients (33 exercising, 11 non-exercising) who were followed-up over a 2 to 6 month period, slight loss of flexion (5.5 degrees) and lateral bend (3 degrees) was observed but there was no change in range of extension. PMID- 8508288 TI - Review of dietary therapy for rheumatoid arthritis. AB - There are now sufficient good scientific studies, from the UK and abroad, to suggest that, at least in some patients with RA, dietary therapy may influence at least the symptoms and possibly the progression of the disease. Since dietary treatment is safe and may reduce or avoid the need for drugs, it is appealing to patients, who are increasingly anxious about potential drug toxicity. It must, however, be medically supervised to avoid misinterpretation of results, to avoid patients taking diets to extremes, with resultant malnutrition, particularly in children, and to prevent patients from persisting with ineffective diets when they should be receiving drug treatment. Medical interest in dietary treatment also ensures that patients discuss their diets with orthodox practitioners rather than being driven by our scepticism into the hands of unqualified people who may exploit patients' interest in the subject. PMID- 8508289 TI - Life-threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagulant coexisting with acquired autoantibodies against factor VIII. AB - A case history of a patient with RA and a lupus anticoagulant coexisting with an acquired inhibitor to factor VIII is described. The factor VIII inhibitor was heralded by life-threatening haemorrhage which followed an invasive procedure. PMID- 8508290 TI - Osseous tuberculosis traced by magnetic resonance imaging in a patient with adult onset Still's disease. PMID- 8508291 TI - Psoriatic arthritis with dyspnoea. PMID- 8508292 TI - Amlodipine in the treatment of Raynaud's phenomenon. PMID- 8508293 TI - Possible danger of cold water. PMID- 8508294 TI - The actions of 5-hydroxytryptamine on the membrane of putative sympatho excitatory neurones in the rostral ventrolateral medulla of the adult rat in vitro. AB - Intracellular recordings were obtained in vitro from neurones lying within the rostral ventrolateral medulla of the adult rat. Neurones could be classified into three groups: silent neurones, irregularly firing neurones which had a regular pattern of action-potential generation. Membrane hyperpolarization of regularly firing neurones failed to reveal underlying EPSPs or disrupt the regular pattern of action-potential generation. Superfusion of a high Mg2+, low Ca2+ aCSF did not abolish action-potential generation but the regular pattern of firing of these neurones was lost. 5-Hydroxytryptamine evoked a slow concentration-dependent hyperpolarization in both spontaneously active and silent neurones, accompanied by a decrease in cell-input resistance. This study has provided further evidence for pacemaker-like neurones within the RVLM and for the modulation of these neurones by 5-hydroxytryptamine. PMID- 8508295 TI - Age-related gliosis in the white matter of mice. AB - A histopathologic study of the brains from 96 mice, ranging in age from 3 to 57 months in age, documents an age-associated increase in hypertrophic astrocytes in white matter. This report of gliosis is distinct from previously reported proliferation of glial cells in the grey matter. Four genotypes, CBA/HT6J, C57BL/6J, B6CBAT6F1J, and B6C3F1 were positive for this age-related lesion. Most very old mice utilized in this study were calorically restricted, a dietary manipulation long known to result in increased longevity in rodents. Caloric restriction appears to delay the age associated increase of this lesion. Immunoperoxidase staining for the astrocyte-specific glial fibrillary acidic protein (GFAP) confirmed the progressive increase in the density of stainable astrocytes with increase in age. GFAP staining of white matter increased in both diet groups with age. These findings present an interesting model for the study of aberrant cellular activity and perhaps neurodegeneration, modulated by caloric restriction. PMID- 8508296 TI - Organization of motor pools supplying axial muscles in the chicken. AB - Intramuscular injections of the retrograde tracers 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate (DiI) and horseradish peroxidase (HRP) were used to map the motor pools innervating axial muscles in the cervical and thoracic regions of the chicken. We found that motor pool position is well correlated with the muscle's embryonic origin, and not necessarily with its position. Muscles of myotomal (exclusively somitic) origin were innervated by medially positioned motoneurons in the median motor column, and the motor pools supplying these muscles were somatotopically organized. Muscles having a dual embryonic origin, from the somites and lateral plate, were innervated by motoneurons positioned further laterally within the median motor column. The relationship between motor pool position and embryonic origin of the muscle may be a general principle of ventral horn organization. PMID- 8508297 TI - Characterization of calretinin-immunoreactive structures in the striatum of the rat. AB - Previous observations have shown that the striatum contains a population of neurones that display immunoreactivity for calretinin. In order to morphologically characterize these neurones, sections of the rat striatum were immunostained to reveal calretinin and examined at both light and electron microscopic levels. The striatum contained a small population of calretinin immunoreactive neurones, which were of medium-size (9-17 microns) and possessed few aspiny, infrequently branching dendrites which tapered to become very thin processes in their most distal portions. Although the calretinin-immunoreactive neurones were homogeneously distributed in the frontal plane, there was a marked rostrocaudal gradient with a much greater density of cells in the rostral than in the caudal parts of the striatum. At the ultrastructural level, calretinin immunoreactive neurones were seen to possess an indented nucleus and to receive synaptic input from at least three types of boutons. In addition to the calretinin-immunoreactive neurones, the striatum also contained axons and terminal boutons that displayed immunoreactivity for calretinin. At least two types of immunoreactive terminals were identified, those forming symmetrical synaptic specialisations and those forming asymmetrical synaptic specialisations. Approximately 50% formed asymmetrical contacts with spines and 30% formed symmetrical synaptic contact with dendritic shafts. In an attempt to further chemically characterize the calretinin-containing neurones, double pre-embedding immunocytochemistry for calretinin and parvalbumin or choline acetyltransferase was carried out and calretinin immunocytochemistry was combined with histochemistry for NADPH-diaphorase. Analysis of these double-stained sections revealed that the population of calretinin-immunoreactive neurones was distinct from the populations of neurones containing parvalbumin, choline acetyltransferase or NADPH-diaphorase. It is concluded that: (1) on the basis of distribution, morphology, chemistry, ultrastructure and afferent synaptic input, the calretinin-immunoreactive neurones are distinct from the major classes of neurones that have been previously recognised in the striatum; (2) calretinin immunoreactive terminals are heterogeneous and are probably derived from local calretinin-containing neurones and possibly other sources. PMID- 8508298 TI - Ornithine decarboxylase-like immunoreactivity in rat spinal motoneurons and motoric nerves. AB - Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the formation of the polyamines putrescine, spermidine and spermine. In the present study ornithine decarboxylase-like immunoreactivity (ODC-LI) was localized immunocytochemically in rat spinal motoneurons, motoric nerves and myoneural junctions in several muscles. In the spinal cord ODC-LI was expressed in most of the large multipolar neurons located in the ventral horn at cervical and lumbar levels. ODC-LI was localized in the cytoplasm, dendrites and axons of the labelled neurons. The nuclei of motoneurons were unlabelled; however, the nuclear membranes and the surrounding cytoplasm were strongly stained. ODC-immunoreactive (IR) axons could be traced through the white matter entering the ventral roots. The myelinated axons in the ventral roots and in the nerve bundles among the muscles were intensely stained with ODC antiserum. The myoneural junctions apposing individual muscle fibers showed ODC-LI with slightly less intensity. Some ODC-IR nerve fibers were seen in the muscle spindles. The present results show that motoneurons in adult rat spinal cored express ODC-LI and that OCD-LI is transported to motoric nerves and myoneural junctions. This suggests that polyamines can be synthesized both in the motoneuron somata and in their peripheral projections. Polyamines may thus regulate cellular functions in all parts of motoneurons. In addition, polyamines may be secreted from their distal projections and have tropic effects on Schwann cells and/or muscular tissue. PMID- 8508299 TI - Cell loss in supraoptic and paraventricular nucleus in Alzheimer's disease. AB - Previous studies have shown an activation of the hypothalamo-neurohypophyseal system (HNS) in normal aging and in senile dementia. Among other explanations, this activation might be secondary to cell loss in the supraoptic (SO) and paraventricular (PV) nuclei. This study reports a 63% loss in the SO and a 56% loss in the PV in a group of Alzheimer disease (AD) patients. The remaining neurons undergo a compensatory hypertrophy that is more pronounced in the SO, affecting cell and nuclear size as well as nucleolar volume. The group of patients with a diagnosis of moderate dementia showed the greatest hypertrophy, as compared to the severely demented patients. Our results suggest that there is a compensatory capacity in the earlier stages of the dementia, that is lost in the final stages of Alzheimer's disease. PMID- 8508300 TI - Quantitative analysis of eyelid movement metrics reveals the highly stereotyped nature of monkey blinks. AB - Blink movement metrics were studied in three alert cynomolgus monkeys using electromagnetic search coils attached to the eyelids bilaterally. Monkey blinks averaged approximately 24 degrees. Down-phase peak velocities were approximately twice those of the corresponding up phases. Most blinks were symmetrical with close temporal linkage of onset and offset between the two eyelids. Monkey blinks exhibited higher peak velocities and shorter durations than have been previously described for similar amplitude movements in humans. Peak velocity vs. amplitude plots were linear and non-saturating within a 45 degrees range for both up and down phases. The relationship between blink peak velocity and average velocity was linear with a slope of approximately 2.0. These values were very similar to those obtained by others, not only for blinks, but also for saccadic eye and ballistic limb movements. Down-phase amplitude-duration behavior could be best described by a linear function with slope < 0.7, while amplitude-duration slope of up phases was best described by a second-order polynomial. Unlike saccadic eye movements, larger amplitude blinks are obtained primarily via increases in peak velocity rather than through extension of blink duration. These data provide mathematical descriptions of monkey blink behavior that indicate the stereotypical nature of blinks. This will serve as a normative data base with which to better understand the neural processing that goes into blinks and will allow the assessment of eyelid movement disorders and evaluation of potential treatments of these disorders. PMID- 8508301 TI - Ventrolateral medulla and sympathetic chemoreflex in the rat. AB - Splanchnic sympathetic nerve discharge (SND), phrenic nerve activity (PND) and putative sympathetic premotor neurons of the rostral ventrolateral medulla (RVL) were recorded in urethane-anesthetized vagotomized rats without aortic baroreceptor afferents. Carotid chemoreceptor stimulation with brief N2 inhalation increased SND by 101 +/- 7%, raised mean arterial pressure (MAP) and increased the discharge rate of RVL premotor neurons by 46 +/- 12% (N = 32). During chemoreceptor activation. SND and most RVL neurons displayed pronounced central respiratory rhythmicity with maximal firing probability immediately after cessation of the PND (postinspiratory phase) and lowest probability during PND (inspiratory phase). Bilateral microinjection of the breed spectrum glutamate receptor antagonist kynurenic acid (Kyn, 5 nmol in 100 nl) into RVL blocked the sympathetic chemoreflex but left the sympathetic baroreflex intact. In contrast, bilateral microinjection of the same dose of Kyn into the caudal ventrolateral medulla (at obex level CVL) blocked the baroreflex but left the sympathetic chemoreflex intact. Bilateral microinjection of the GABAA agonist muscimol (87.5 pmol in 50 nl) into CVL produced effects identical to those of Kyn. These results confirm that the caudal ventrolateral medulla contains an essential relay of the sympathetic baroreflex and demonstrate that the same area plays no role in the sympathetic chemoreflex. The data suggests that these two reflexes could have a largely independent course through the medulla oblongata and that integration between the baroreceptor and chemoreceptor information used for sympathetic vasomotor control may occur as late as the premotor neuronal stage in RVL. PMID- 8508302 TI - Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat. AB - Responses of the subthalamic nucleus (STH) neurons to the stimulation of the sensorimotor cortex (Cx) were recorded in intact rats and in those which received lesions in the pallidum, the neostriatum, the brainstem, or the corpus callosum. Most of the STH units (78%) exhibited two excitatory peaks which were interrupted by a brief period of inhibition. Some of units which were located in the peripheral part of the STH tended to lack the brief inhibitory component and exhibited a long period of excitation. These excitations were followed by a long lasting inhibitory period. Intracellular recording indicated that these responses were EPSPs interrupted by a short IPSP and a long period of disfacilitation of Cx inputs. A quinolinic acid lesion of the neostriatum and a knife cut of the brainstem failed to alter these responses, while an ibotenic acid lesion of the globus pallidus abolished the short inhibition seen in the midst on the excitation. Stimulation of contralateral Cx also evoked excitatory responses in the STH. The responses were completely eliminated by a parasagittal knife cut of the rostral part of the corpus callosum. PMID- 8508303 TI - Morphological and membrane properties of young rat lumbar and thoracic dorsal root ganglion cells with unmyelinated axons. AB - Membrane and morphological properties of thoracic (Th9-13) and lumbar (L2-5) dorsal root ganglion cells have been investigated in an in vitro dorsal root ganglion (DRG) preparation from 14-day-old rats using intracellular recordings and the intracellular injection of Neurobiotin. The passive and active membrane properties of 47 DRG cells with conduction velocities (CV) less than 0.81 m/s were studied, which were considered to possess unmyelinated axons. The action potentials elicited by the stimulation of peripheral nerves or the dorsal roots were characteristic of C-cells, with long duration, inflexion on the falling phase and long lasting after hyperpolarization. Input resistance of the C-cells varied between 16 and 158 M omega and were significantly higher in thoracic than in the lumbar ganglia. Cells in the more cranial levels also tended to be smaller than those in the caudal levels with a mean cross sectional area of 301 +/- 32.5 microns2. Twenty-five percent of the cells from both regions showed an inward rectification. The distribution of CVs, input resistances and cross sectional areas were non-normal. While a weak correlation was found between the conduction velocity and input resistance of the cells, no correlation was present between the size of the perikarya and conduction velocity or the input resistance. These results show that by the 14th day of postnatal development membrane and morphological parameters approach those of adult rats. They also suggest that in cells with unmyelinated fibres, the size of the perikaryon does not predict the thickness of the axon, and that this cell population is heterogeneous. PMID- 8508304 TI - Increased sensitivity to adenosine in the rat dentate gyrus molecular layer two weeks after partial entorhinal lesions. AB - The molecular layer of the dentate gyrus exhibits extensive circuit and receptor reorganization after entorhinal lesions and in Alzheimer's disease, including decreased adenosine (A1) receptor binding in the terminal zone of damaged perforant path fibers. We examined the adenosine-sensitivity of evoked synaptic activity recorded from the rat dentate gyrus molecular layer in hippocampal slices prepared after electrolytic lesions were placed in approximately the middle third of the entorhinal cortex. Extracellular field potentials (EFPs) recorded in slices prepared from animals two days post-lesion were small, upward going, and exhibited paired-pulse potentiation, but by two weeks post-lesion EFPs had recovered to large, downward-going responses that exhibited paired-pulsed depression. EFPs recorded from two week post-lesion slices were about 2-fold more sensitive (P < or = 0.05) to exposure to adenosine when compared to EFPs recorded from slices from unlesioned animals. Adenosine-induced reduction of paired-pulse depression was similar between unlesioned and post-lesion slices. AChE histochemistry performed after recording revealed dense staining in the dentate gyrus molecular layer of post-lesion slices as compared to slices from unlesioned animals, confirming that sprouting of cholinergic fibers occurred as expected from previous entorhinal lesion studies. Autoradiography performed on adjacent slices showed a decrease in binding to A1-adenosine receptors in the dentate gyrus molecular layer in post-lesion slices as compared to slices from unlesioned animals, indicating that there was a loss of presynaptically located A1-adenosine receptors on damaged perforant pathway terminals. These results indicate that, in addition to the recovery of the major excitatory signal to the hippocampus after entorhinal cell loss, this signal is more sensitive to modulation by adenosine, suggesting an increase in A1-adenosine receptor efficacy in the reinnervated region. PMID- 8508305 TI - Electrophysiological actions of oxytocin in the dorsal vagal complex of the female rat in vitro: changing responsiveness during the oestrous cycle and after steroid treatment. AB - The effect of the oxytocin-specific agonist Thr4,Gly7-oxytocin (TGOT) was tested on neurones in tissue slices of the dorsal vagal complex, obtained from virgin female rats at different stages of the oestrous cycle. The proportion of neurones excited by TGOT (0.1 microM) was independent of the day of the cycle, but both the basal activity and magnitude of response induced by TGOT were significantly reduced on the day of oestrus by comparison with dioestrus. This was due to a small but significant shift in the dose-response relationship. The magnitude of the excitation of neurones obtained from animals at proestrus did not differ significantly from either oestrus or dioestrus, but lay between the two. Ovariectomy 6 days prior to recording reduced the proportion of responsive neurones (35% vs. 69% at dioestrus), but had only a small effect on the amplitude of the averaged responses. Daily injection of 10 micrograms oestradiol benzoate had no additional effect on the proportion of responsive neurones (40%), but caused a marked suppression of the amplitude of the response at all doses (change in firing rate caused by 0.1 microM: 1.68 +/- 0.27 Hz vs. 2.69 +/- 0.39 Hz). In contrast, injections of 5 mg progesterone caused a small increase in the amplitude of the response. The data show that ovarian steroids have a marked effect on oxytocin-sensitive neurones of the dorsal vagal complex, causing dynamic changes in responsiveness over the oestrous cycle. This is discussed with respect to the effects of ovarian steroids on central oxytocin receptors and the possible involvement in regulating autonomic functions. PMID- 8508306 TI - The proportion of amphiphilic choline acetyltransferase in Drosophila melanogaster is higher than in rat or Torpedo and is developmentally regulated. AB - We show that in the central nervous system of the fly, Drosophila melanogaster, choline acetyltransferase (ChAT) activity exists under two molecular forms, a soluble, hydrophilic form and a membrane-bound, amphiphilic form. This is based on the following demonstrations of differential solubilization and interaction with non-denaturing detergents: sequential extraction of Drosophila heads produced low-salt-soluble (83-87%) and detergent-soluble (6-7%) ChAT activity. Sedimentation in sucrose gradients of detergent-soluble ChAT was found to be influenced by the type of detergent present in the gradient (Triton X-100 and Brij 96). This was not the case for low-salt-soluble ChAT. To further confirm these findings, we subjected Drosophila heads to Triton X-114 fractionation. This method, which yielded 12% of amphiphilic ChAT activity, separates hydrophilic from amphiphilic proteins. Compared to central nervous tissue of rat and Torpedo electric lobes, Drosophila head contained the highest proportion of amphiphilic ChAT activity. Synaptosomes isolated from Torpedo electric organ exhibited higher levels of amphiphilic ChAT than did electric lobes. Of the three animal species analyzed here, the Torpedo amphiphilic enzyme was the most hydrophobic and the rat enzyme the least hydrophobic. The proportion of amphiphilic ChAT was analyzed during Drosophila development. The percentage of this activity increased about 7 times from embryo to larva and then remained constant until the adult fly age. PMID- 8508307 TI - Acrylamide induces immediate-early gene expression in rat brain. AB - Northern blot analysis was used to study the effects of acrylamide, a potent neurotoxin, on the induction of c-fos and c-jun mRNA in rat brain. Male Sprague Dawley rats (10-12 weeks old) treated with acrylamide as a single dose (100 mg/kg, i.p.) or via drinking water (0.03% w/v) for 4 weeks, were used to study acute and chronic effects on immediate-early gene expression, respectively. Acute administration of acrylamide caused a statistically significant increase in the expression of c-fos (approx. 37%) and c-jun (approx. 17%) mRNA in rat brain. By contrast, the level of c-fos mRNA in chronic acrylamide treatment was not altered significantly, but the expression of c-jun mRNA was increased almost 100% as compared to control. These data show that the neurotoxin acrylamide induces immediate-early gene expression in the brain. The effects appear to be related to the route of administration, dose and duration of acrylamide treatment. PMID- 8508308 TI - Total numbers of various cell types in rat cerebellar cortex estimated using an unbiased stereological method. AB - A new and efficient stereological method for estimating the total number of the different cell types in rat cerebellar cortex is presented. The cells have been subdivided into the following categories: Purkinje cells, granule cells, Golgi cells, glial cells in the granular layer, Bergmann glial cells and neurons and glial cells in the molecular layer. The method has been used to estimate the total number of some of the cell types in rats exposed to orally administered toluene at doses of 200, 400 and 800 mg/kg/day for 12 weeks compared with a control group. No statistically significant differences were found between the exposed and non-exposed animals. The described method can be used in a number of both biological and experimental studies. With the use of new stereological methods it is possible to get precise estimates of total cell numbers in a much shorter time than earlier required. This makes it possible to improve the reliability of the final result by increasing the number of cases processed. PMID- 8508309 TI - Hypertrophic neurons innervating the urinary bladder and colon of the streptozotocin-diabetic rat. AB - Female rats were made diabetic with an intravenous injection of streptozotocin (STZ) producing bladder hypertrophy. Using fluorescent dyes injected into the bladder or the colon, we have measured the size of neurons in various ganglia associated with these organs in control and STZ-diabetic rats. These include (1) postganglionic neurons in the pelvic ganglion, (2) postganglionic neurons in the inferior mesenteric ganglion, (3) dorsal root ganglion neurons, (4) sympathetic chain ganglion neurons, (5) preganglionic neurons in the sacral parasympathetic nucleus, (6) motor neurons in Onuf's nucleus innervating the external urethral sphincter. In addition we have measured neurons in some of these groups for rats which have been maintained on a 5% sucrose in water and restricted food diet. In the STZ-diabetic animals only those neurons which make direct contact with the bladder or the colon were found to be hypertrophied (15-70%). In the diuretic animals, only neurons directly innervating the bladder exhibited hypertrophy. We speculate that a trophic factor transported from the organ to the neuron is responsible for this effect. PMID- 8508310 TI - Numerical data on neocortical neurons in adult rat, with special reference to the GABA population. AB - The disector method was used to estimate the numerical density of neurons (number per unit volume) and their actual number per column (number under a given area of pial surface), in the occipital (monocular segment of the primary visual area, Oc1M), the parietal (somatosensory barrelfield area, Par1) and the frontal cortex (primary motor area, Fr1) of adult rat. Values were first obtained for all neurons in each layer, and then for GABA neurons as identified with postembedding immunocytochemistry on semithin sections. The numerical density of neurons in the frontal cortex (34,000/mm3) was significantly lower than in the two other neocortical areas (occipital: 52,000; parietal: 48,000/mm3). The GABA population showed a similar difference and consequently represented an equivalent proportion of total (15%) in the three cortical areas. Across layers, there was an alternate distribution of low and high density of neurons from layers II-III to VI in the three cortical areas, with the highest density in layer IV of the two sensory areas. The laminar changes in density of the GABA neurons were not as pronounced as those of the overall population. Consequently, the layers with the highest overall neuronal densities tended to have a lower proportion of GABA neurons and vice versa. There were more neurons under 1 mm2 of surface in the parietal (90,000) than the occipital or the frontal cortex (71,000), which was also true of the GABA neurons. The greater number of neurons per column in the parietal cortex was mostly imputable to layer IV, the main recipient of thalamic axons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508311 TI - Methylprednisolone reduces excitatory amino acid release following experimental spinal cord injury. AB - Administration of methylprednisolone within several hours after injury to the spinal cord has been shown to reduce subsequent impairment in humans and experimental animals. Secondary damage following initial trauma is probably caused in part by the toxicity of released excitatory amino acids. We demonstrate here that methylprednisolone reduces the release of excitatory amino acids following experimental spinal cord injury in rats. PMID- 8508312 TI - Endogenous adenosine delays the onset of hypoxic depolarization in the rat hippocampus in vitro via an action at A1 receptors. AB - The effect of endogenous adenosine on the delay to hypoxic depolarization (HD) was examined utilizing in vitro slices of gerbil hippocampus. Adenosine receptor antagonists were used to block the actions of adenosine during hypoxia, and the delay to HD was measured in the CA1 region. Both a broad spectrum antagonist (theophylline) and an A1 receptor-specific antagonist (8-cyclopentyl-1,3 dimethylxanthine; CPT) shortened the delay to HD. These findings indicate that endogenous adenosine working through A1 receptors prolongs the delay to HD. This effect may contribute to the neuroprotective influence of adenosine and its analogs. PMID- 8508313 TI - Extraneuronal noradrenaline in the prefrontal cortex of morphine-dependent rats: tolerance and withdrawal mechanisms. AB - The changes in extracellular concentrations of noradrenaline (NA) in the prefrontal cortex of morphine-dependent rats were studied by microdialysis following an acute morphine challenge and during naloxone-precipitated withdrawal. Animals were implanted with morphine- or placebo-containing pellets for 5 days. In control rats a challenge dose of morphine (5 mg/kg s.c.) induced a maximum decrease in NA output of about 45% of pre-drug levels. In contrast, morphine challenge had no effect on extraneuronal NA concentrations in morphine implanted animals. In control animals, naloxone (2 mg/kg i.p.) produced no behavioral effect nor changed NA levels. However, in morphine-dependent animals naloxone suddenly increased extraneuronal NA by 175% of baseline dialysate levels in the first sample after the injection and precipitated a morphine-withdrawal symptomatology that paralleled the changes in NA output. Thus, chronic morphine treatment in rats results in the development of tolerance to the acute inhibitory effect of morphine on extraneuronal NA and is associated with a stimulation of prefrontocortical NA output during naloxone-precipitated withdrawal. PMID- 8508314 TI - Cholinergic marker deficits induced by lesions of the nucleus basalis of Meynert are attenuated by nerve growth factor in young, but not in aged, F344 rats. AB - To investigate the efficacy of nerve growth factor (NGF) in promoting recovery from cholinergic damage, young (3-4 month old) and aged (22-23 month old) Fischer 344 rats received NMDA-induced unilateral lesions of the nucleus basalis of Meynert and subcutaneous osmotic pumps (2-week duration) connected to permanently implanted cannulas directed at the lateral ventricle ipsilateral to the lesion. Pumps were filled with either artificial CSF/rat serum albumin (the vehicle) or 5.0 micrograms of angiotensin-free, beta-NGF. Fourteen days after surgery, all subjects were sacrificed and their brains regionally dissected (frontal and occipital cortices, striatum, and dorsal and ventral hippocampi) and assayed for choline acetyltransferase (CAT) and acetylcholinesterase (AChE). Results indicated that the lesion decreased CAT and AChE levels within the frontal cortex of both young (29.8% and 39.4% depletion, respectively) and aged (30.5% and 34.8% depletion, respectively) animals. Only in young animals did NGF reduce these lesion-induced CAT (by 34.2%) and AChE deficits (by 65.5%). In fact, NGF exacerbated frontal cortical CAT depletions in aged animals in that percent depletion was 11.3% more following treatment (30.5% vs. 41.8% depletion in Aged/CSF and Aged/NGF groups, respectively). Lower CAT and AChE levels were found in the striatum of aged animals, an effect not reversed by NGF treatment. In contrast, NGF in young animals enhanced striatal CAT activity on the non-lesioned side by 22.2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508315 TI - Differential responses of barosensitive neurons of rostral ventrolateral medulla to hypoxia in rats. AB - We examined the responses to hypoxia of 48 spontaneously active barosensitive neurons of the rostral ventrolateral medulla (RVL) of anesthetized rats. Twenty nine projected to the spinal cord while 19 did not. All spinal barosensitive neurons increased their discharges in advance of an elevation of arterial pressure in the presence or absence of arterial chemoreceptors. In contrast, 18/19 of the non-spinal barosensitive neurons were not excited by hypoxia. The results indicate that barosensitive RVL neurons consist of two populations differing in efferent pathway and responsivity to hypoxia and that the spinal barosensitive RVL neurons are functionally discrete and selectively sensitive to hypoxia. PMID- 8508316 TI - 7S nerve growth factor has different biological activity from 2.5S nerve growth factor in vitro. AB - It is considered that two molecular forms of nerve growth factor (NGF), that is 7S NGF and 2.5S NGF have the identical neurotrophic effect on neurons. We now report that 7S NGF has different biological activities from 2.5S NGF in vitro. 7S NGF could promote the survival and neurite outgrowth of neurons from newborn rat hippocampus, cortex and cerebellum and stimulate the proliferation of astrocytes in vitro, but 2.5S NGF had no such effect. PMID- 8508317 TI - Role of the corpus callosum in expression of behavioral asymmetries induced by a unilateral dopamine lesion of the substantia nigra in the rat. AB - The present study examines the effects of sectioning the corpus callosum on the expression of asymmetric behaviors induced by a unilateral 6-hydroxydopamine (6 OHDA) lesion of the substantial nigra. Severing the corpus callosum eliminated the asymmetry in spontaneous investigation of edges in an open-field, without affecting total time of investigation. In contrast, callosotomy reduced the magnitude of externally cued turning, but failed to affect the directional distribution of responding. Moreover, it reduced the magnitude of apomorphine- but not amphetamine-induced turning. It is suggested that transcallosal communication is required for those behavioral asymmetries induced by a unilateral dopamine lesion which depend on head, rather than whole body movements. PMID- 8508318 TI - Effect of ageing on extracellular ascorbate concentration in rat brain. AB - In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of ageing on extracellular ascorbate (AA) concentration in the rat brain. Recordings from the nucleus accumbens in 3-, 6- and 18-month-old Sprague-Dawley rats revealed an age-related decrease in basal extracellular AA concentration. The mean AA current measured in 18-month-old rats was less than 10% of the current measured in 3-month-old rats. Systemic administration of ethanol (1.0 g/kg, i.p.) caused an increase in the AA signal measured in this area in all 3 age groups tested. However, the effect on AA was significantly less pronounced in 18-month-old rats. Further analysis of the AA signal revealed a gradual increase in AA release during terminal anoxia. Also in this case the effect on AA was significantly less pronounced in 18-month-old rats. This difference was also observed in the caudate putamen, another dopamine (DA) rich area in the brain. No significant difference in AA release was observed in the frontal cortex where the DA concentration is low. The increase in AA was followed by a pronounced increase in extracellular DA in the nucleus accumbens and caudate putamen. This release of DA was accompanied by a prompt reversal of the AA signal possibly explained by a DA-dependent autoxidation of AA. These results suggest a role for brain AA in the process of ageing. PMID- 8508319 TI - In situ quantitative estimates of the age-related and diabetes-related changes in cerebral endothelial barrier antigen. AB - To determine whether ageing or diabetes, conditions known to alter the blood brain barrier (BBB) is associated with changes in endothelial barrier antigen (EBA), a rat BBB-specific protein, in situ quantitation of forty vibrotome sections of cerebral tissue of 5 young (4 months old), 5 aged (26 months old) and 5 streptozotocin-induced diabetic rats after 4 weeks of diabetes were studied using immunohistologic techniques. The anti-EBA-stained microvessels were normalized against the total microvessels identified with either anti-EBA binding or anti-Glut-1 binding. The results indicate that the EBA-stained microvessels of the hippocampus, but not of other cerebral cortical areas or white matter, are reduced in aged rats (88.02 +/- 2.19% vs. 80.65 +/- 2.44%, P < 0.01). There were no significant changes in the diabetic rats. These results support the notion that changes in the BBB correlate with the aging of the central nervous system. PMID- 8508320 TI - An in vitro circadian rhythm of melatonin sensitivity in the suprachiasmatic nucleus of the djungarian hamster, Phodopus sungorus. AB - Past studies in the rat and Syrian hamster show that metabolic and electrical activity of the suprachiasmatic nuclei (SCN) is inhibited by melatonin (MEL) at about circadian time (ct) 8-11 h. The present experiment examined the effect of MEL on the firing frequency of SCN cells in brain slices prepared from long day (LD 16:8) Djungarian hamsters to determine the timing of MEL sensitivity and if sensitivity persists in vitro. Pressure ejection of MEL (2 mM in 165 mM NaCl) suppressed the firing rate of 26% of SCN neurons recorded, excited 13%, and had no effect on 61% of the 161 cells tested. MEL elicited the highest percent response (64%) during the 4-h time bin immediately preceding the dark phase of the projected light:dark cycle on day 1 (ct 8-12 h). A similar temporal pattern of MEL sensitivity was found during the second day of recording. In contrast, application of vehicle to 52 SCN cells had little effect on firing rate. These results demonstrate that a sensitivity rhythm to MEL is present in the SCN of the Djungarian hamster and persists with a period of about 24 h in vitro. PMID- 8508321 TI - Changes in activity and mRNA for rat tryptophan hydroxylase and aromatic L-amino acid decarboxylase of brain serotonergic cell bodies and terminals following neonatal 5,7-dihydroxytryptamine. AB - In the present study, we examined time-dependent changes in activity, mRNA and immunoreactivity of the serotonin biosynthetic enzymes, tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC) in dorsal raphe nucleus (DRN), caudal brainstem and hypothalamus, following intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal rats. TPH activity in central serotonergic cell bodies and terminals was reduced to 20-30% of control levels at 1-8 weeks after neonatal, low-dose 5,7-DHT injection (24 micrograms free base). In contrast, AADC activity was either not changed or decreased to 40% of control levels, depending on the region. In situ hybridization and immunocytochemical staining indicated that 5,7-DHT caused a marked reduction in TPH and AADC message levels as well as the number of 5-HT and AADC-immunoreactive cells within the DRN as early as 1 week after 5,7-DHT. Even 15 weeks after drug administration recovery did not occur. This apparent neuronal loss was region-specific suggesting that some serotonergic neurons are more resistant to neonatal 5,7-DHT treatment than others. Taken together, these studies indicate that neonatal treatment with 5,7-DHT produces a marked and permanent (up to 15 weeks) reduction in the number of central serotonergic neurons. PMID- 8508322 TI - Protective effects of calpain inhibitors against neuronal damage caused by cytotoxic hypoxia in vitro and ischemia in vivo. AB - The calpains are calcium-dependent intracellular proteases that are activated in a number of pathogenic conditions. We tested the capacities of protease inhibitors, calpain inhibitor I and leupeptin, to protect against the neuronal degeneration caused by cytotoxic hypoxia or transient global cerebral ischemia. Primary neuronal cultures were prepared from embryonic chick telencephalon, and cytotoxic hypoxia was induced by adding 1 mM NaCN to the culture medium for 30 min. Global ischemia was induced in rats by clamping both carotid arteries and lowering the arterial blood pressure to 40 mmHg for 10 min. Both calpain inhibitor I and leupeptin protected neurons against ischemic and hypoxic damage. Neuroprotection was indicated by increased cell viability and protein content in the cultures, and fewer damaged neurons in the hippocampal CA1-subfield. Thus, blockade of proteolysis can protect neurons against cytotoxic and ischemic damage. PMID- 8508323 TI - D2 dopamine receptor distribution in the rodent CNS using anti-peptide antisera. AB - D2 dopamine receptors were identified immunohistochemically in rodent tissues using anti-peptide antisera to distinguish regional and cellular staining patterns. These subtype selective polyclonal antibodies were directed against both extracellular and intracellular regions of the native protein and showed that the D2 dopamine receptors are widely distributed within the nervous system. The highest expression of D2-like dopamine receptor immunoreactivity was visualized in the forebrain and components of the basal ganglia, supportive of previous investigations of the D2 dopamine receptor distribution using in vitro autoradiographic ligand binding or in situ hybridization for its messenger RNA. The anti-peptide antisera could detect the dopamine receptor in both perfusion fixed and fresh-frozen tissue preparations. The reactive cells and their processes could be distinguished using experimental incubations from 1:8,000 (in immunofluorescence processing) to 1:80,000 (in immunoperoxidase processing) in the most reactive nervous system region, the neostriatum. The antisera are selectively directed against extracellular or intracellular epitopes in both the long and short isoforms of the D2 dopamine receptor, and should prove useful in subsequent studies of the subcellular distribution of this receptor in particular, and the dopamine system in general. PMID- 8508324 TI - Lack of the development of morphine tolerance in experimental amnesia: role of arginine vasopressin. AB - The development of tolerance to morphine analgesia in amnesic model mice and the role of arginine vasopressin (AVP) in the underlying mechanism was examined. Hypoxia, brain ischemia, scopolamine and electroconvulsive shock (ECS) manipulation caused amnesia in the step-through type passive avoidance learning test performed at 24 h after the training trial. The amnesic state lasted for at least 3 days and recovered to naive control level on the 20th day after each manipulation. In all amnesic groups, radioimmunoassayable AVP content in hypothalamus was decreased, in particular, the reduction was significant in hypoxia and ischemic induced amnesic animals, then recovered to the control level by 20 days after each treatment. Daily morphine, 10 mg/kg, s.c. easily resulted in the development of tolerance to the analgesic effect in control animals; however, such treatment failed to develop tolerance in amnesic model animals, leaving the analgesic effect unchanged to the control levels. Daily pretreatment with i.c.v. AVP, dose-dependently reinstated the development of tolerance in amnesic model mice. When morphine injection was started from 20 days after the amnesia inducing treatment, tolerance developed as in a similar pattern as in control animals. Thus, amnesic model mice are deficient in brain AVP levels, and consequently, a certain level of AVP in the hypothalamus is required for maintaining the normal function such as the development of tolerance to morphine and the recovery from amnesia. PMID- 8508325 TI - Binding the suffering into our community: on physician-assisted suicide. PMID- 8508326 TI - Cardiovascular disease in Canada. PMID- 8508327 TI - Diastolic dysfunction of the left ventricle in systemic hypertension. PMID- 8508328 TI - Endocarditis caused by MAI infection. PMID- 8508329 TI - A new possibility in the study of heart activation: the nondipolar body surface map. AB - The main goal of the present paper is to study the temporal and spatial course of cardiac electrical activation noninvasively, and to acquire more information than can be obtained from conventional methods, such as electrocardiography or vectorcardiography. The single moving resultant heart dipole is determined from a set of measured body surface potential maps before dipolar and nondipolar theoretical body surface potential maps are calculated. These three kinds of maps are studied together in different electro-cardiological situations (normal, left and right bundle branch block, and necrosis) during the entire cardiac cycle. The set of nondipolar maps is suitable for localizing and following the changes of minor positivity and negativity to detect small extensions of infarcts. PMID- 8508330 TI - The hospital course and short term prognosis of patients presenting to the emergency room with decompensated congestive heart failure. AB - OBJECTIVES: This observational study was done to describe the characteristics, hospital course and short term prognosis of patients presenting to an emergency room with decompensated heart failure and to determine the parameters influencing the length of their hospital stay. DESIGN: The routine clinical and laboratory characteristics of consecutive patients presenting to an emergency room with decompensated heart failure were documented and the patients followed for six months. SETTING: One teaching hospital and one community-based hospital in Montreal, Quebec. PATIENTS: A prospective cohort of 153 consecutive patients presenting to the emergency room with decompensated heart failure. Follow-up was by clinic visit and telephone survey at one, three and six months. Follow-up was 100%. MEASURES OF OUTCOME: Length of hospital stay, in-hospital mortality, readmissions and after hospital discharge deaths were measured. RESULTS: The average length of hospital stay was 6.2 days with a skewed distribution ranging from one to 56 days. A multivariate analysis showed that the length of hospital stay was associated with increasing left atrial size (P < 0.05), an ischemic etiology of the heart failure (P < 0.03) and a slow response to diuretic therapy (P < 0.001). This mathematical model accounted for only a small amount of hospital stay variability (R2 = 0.22). Six month mortality and morbidity of these patients was high, with 23% dying and 30% readmitted for heart failure, but was independent of the duration of the initial hospitalization. CONCLUSIONS: This prospective study confirms that the hospital course for congestive heart failure is shortening. The six month prognosis of patients presenting to an emergency room for decompensated heart failure is poor and appears independent of the length of hospital stay. PMID- 8508331 TI - Measurement errors in standard visual analysis of coronary angiograms: consequences on clinical trials. AB - OBJECTIVE: The usual assessment of coronary angiograms by standard visual analysis was compared with the assessment by quantitative computer analysis to provide evidence of the consequences of measurement errors attributable to visual assessment in the evaluation of coronary stenoses in clinical trials. METHODS: Angiograms obtained in 151 patients enrolled in a double-blind randomized controlled trial assessing the effect of fish oil supplementation on restenosis were evaluated by both visual and quantitative methods. Proportions of patients with unsuccessful angioplasty and proportions of patients with restenosis according to visual and quantitative methods were compared by standard statistical methods. RESULTS: Of the 151 patients who were considered successfully dilated by visual interpretation, 32 were not considered successfully dilated by quantitative analysis. With quantitative computer analysis, evaluation of restenosis on the 119 successfully dilated patients documented a protective effect of fish oil against restenosis (30.5% of treated patients versus 48.3% of control patients, P < 0.05). Visual evaluation of restenosis six months after angioplasty misclassified 10% of patients in each treatment group and failed to demonstrate a protective effect of fish oil against restenosis. CONCLUSIONS: Misclassification by visual assessment of both success and restenosis in the present trial led to underestimating the true effect of fish oil in the prevention of restenosis. Accurate and objective methods, such as quantitative computer analysis, are thus required for evaluating the effects of interventions on coronary arteries. PMID- 8508332 TI - Intermittent intravenous amrinone infusion: a potentially cost effective mode of treatment of patients with refractory heart failure. AB - OBJECTIVE: To describe the experience of 41 New York Heart Association (NYHA) class III and IV heart failure patients treated with intermittent intravenous amrinone infusions in addition to conventional therapy. BACKGROUND: Congestive heart failure is a condition often requiring repeated admission to hospital. Accordingly, a treatment modality which can reduce the number of admissions is desirable and potentially cost-effective. DESIGN: Retrospective analysis of data from hospital and office charts. SETTING: Community hospital with 640 active beds. INTERVENTION: The initial amrinone infusion was administered in the hospital under electrocardiographic monitoring; subsequent infusions were given in an out-patient unit. A bolus injection of 0.75 mg/kg followed by an infusion of 5 to 10 micrograms/kg/min for 8 to 12 h was administered every two to six weeks as clinically indicated. RESULTS: Results are reported for the first 51 months. Sixty-six per cent of the patients improved their NYHA class, 34% remained unchanged or deteriorated. Survival paralleled that of other studies involving similar patients not receiving nonglycoside positive inotropes. The number of days spent in the hospital in the six months after starting on amrinone compared with the six months before treatment was reduced to 50% (P < 0.05), and the number of hospital admissions in the six months after starting amrinone compared with the six months before decreased to 56% (P < 0.05). CONCLUSIONS: Intermittent intravenous amrinone infusions can be given in an out-patient setting in patients with NYHA class III to IV heart failure. This program is cost effective, reducing hospital admissions and in-patient hospital days. PMID- 8508333 TI - Cerebral circulation dysfunction and hemodynamic abnormalities in syncope during upright tilt test. AB - OBJECTIVE: To assess the hemodynamic features, including monitoring of cerebral circulation, blood pressure and heart rate, in syncope patients during upright tilt test. DESIGN: Nonrandomized sequential patients with history of syncope of uncertain etiology compared with healthy subjects. SETTING: Noninvasive hemodynamic laboratory of a tertiary referral centre. PATIENTS: Twenty patients with history of syncope and 10 controls without syncope. PROCEDURES: Transcranial Doppler measurement or middle cerebral artery flow velocity, noninvasive and invasive blood pressure monitoring, electrocardiography and pulse oximetry monitoring during upright tilt testing. Measurements were taken in patients at the height of symptoms in supine and upright posture. MAIN RESULTS: Ten patients, while still normotensive, had a drop of 53 +/- 10% (mean +/- SD) in cerebral bloodflow velocity (P = 0.0001) and an increase in heart rate by 58 +/- 35%. The remaining 10 patients had a 58 +/- 15% reduction in cerebral bloodflow velocity (P = 0.0001), a drop in blood pressure of 33 +/- 8% (P = 0.0001) and no change in heart rate. The controls showed no significant changes in cerebral bloodflow velocity and a 25 +/- 12% increase in heart rate (P = 0.0002). CONCLUSIONS: Transcranial Doppler monitoring of cerebral bloodflow velocity during upright tilt testing may improve insight into the complex physiology of syncope. PMID- 8508334 TI - Use of acetylsalicylic acid to improve patency of subclavian to pulmonary artery Gore-Tex shunts. AB - In order to assess the influence of acetylsalicylic acid (ASA) on function and patency of Gore-Tex shunts, angiographic features of 62 Gore-Tex shunts were assessed, 31 without and 31 with postoperative ASA. Groups were selected on the basis of similar angiographic follow-up duration. Mean follow-up was 709 days for the group without ASA and 739 days for the group with it. The average daily dose of ASA was 4.5 mg/kg/day started a mean of 6.7 days after surgery. Clinical characteristics were similar between the two groups except for age at surgery which was 581 days in the group without ASA (operated between 1983 and 1987) and 303 days in the group with (operated between 1987 and 1991), reflecting the fact that patients were operated upon earlier after 1987. Preoperative Gore-Tex diameter was similar between the two groups, but three patients in the group with ASA had a Gore-Tex shunt as small as 4 mm. At angiography, four conduits were diagnosed as nonpatient (two in each group), 20 had a localized stenosis (11 of 28 in the group without ASA and nine of 23 in the group with ASA). Patency index (angiographic Gore-Tex diameter/preoperative Gore-Tex diameter) was similar in the two groups: 68.5% in the group without ASA and 69.7% in the group with ASA. Pulmonary artery growth index was 57% in the group without ASA and 91% in the group with ASA. No risk factor for thrombosis or decreased patency was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508335 TI - Screening for antimalarial toxicity. PMID- 8508336 TI - [Anterior segment inflammation in cataract operation: comparison of intraocular lens implanted in the lens capsule and in the sulcus]. AB - Intracapsular implantation of an intraocular lens (IOL) after cataract extraction is considered to be more "physiologic" than sulcus implantation. Using a laser flare-cell meter, we measured the degree of anterior segment inflammation in 24 eyes with an IOL implanted in the sulcus and 14 eyes with an IOL implanted "in the bag." All patients were followed for 1 year. The mean flare value was significantly lower in the bag-implanted eyes than in the sulcus-implanted eyes 1 day (p = 0.009) and 3 days (p = 0.012) after surgery; no significant difference in degree of flare was found between the groups after that time. At 1 year the sulcus-implanted group was found to have slightly higher flare values than a control group of 34 unoperated patients matched for age. Although this difference was statistically significant (p = 0.012), it should not be considered clinically relevant. PMID- 8508337 TI - Quadruple therapy for ocular toxoplasmosis. AB - Between Dec. 1, 1973, and May 30, 1989, 36 patients (37 eyes) with ocular toxoplasmosis seen at a uveitis clinic received quadruple therapy (pyrimethamine, trisulfapyrimidines, clindamycin and prednisone). The criteria for quadruple therapy were active lesions involving or threatening the macula or the optic disc, or a visual acuity of 20/70 or worse due to vitreous opacification caused by active inflammation. All but four of the cases showed improved vision. A total of 54% of the cases responded favourably within 2 weeks after the start of treatment, and 81% responded within 3 weeks. Patients took pyrimethamine for 1 to 2 weeks and received trisulfapyrimidines and clindamycin for 3 weeks, with a tapering course of orally given prednisone. The only complication was skin rash secondary to trisulfapyrimidine therapy, in four cases. None of the patients manifested diarrhea, pseudomembranous colitis or bone marrow suppression. The length of follow-up ranged from 1 month to 15.5 years. There were seven recurrences in five patients, five of which responded to a second course of quadruple therapy. PMID- 8508338 TI - Experimental treatment of eyelashes with high-frequency radio wave electrosurgery. AB - Apart from mechanical epilation, which is a nuisance to both the patient and the ophthalmologist, standard techniques for removing unwanted eyelashes, such as electrosurgery (Hyfrecator) and cryosurgery, may cause eyelid tissue damage and other complications. Refinements in electrosurgical techniques have enabled production of a machine that can provide high-frequency radio waves with a modification of the waveform to produce a blended cut-coagulation effect (Ellman Surgitron). Treatment of hairs in fresh calf skin with the Ellman Surgitron resulted in destruction of the germinal cells of the hair follicle, with only a small amount of tissue change lateral to the track of the electrode; the Hyfrecator caused total sloughing of the epithelial cells, with marked superficial tissue changes due to heat spread. In six eyelids of six patients undergoing eyelid excision the Ellman Surgitron was effective in causing destruction of the germinal cells of the hair follicle, with very little lateral heat spread in the tissues or destruction of the skin epithelial cells. As well, there was no tissue damage anywhere near the conjunctival surface. PMID- 8508339 TI - [Keratometric characteristics and astigmatism of globes from eye bank]. AB - We measured by means of keratometry the dioptric power of the main meridians of 142 globes (79 subjects) obtained from an eye bank. The mean dioptric power was 43.56 (standard deviation [SD] 1.97) dioptres. Eyes from female subjects had a significantly higher mean power than those from male subjects (p < 0.05). The keratometric readings were used to quantify corneal astigmatism. The mean degree of astigmatism was 1.03 (SD 0.95) dioptres. There was no significant difference in the amount of astigmatism between age groups, between eyes from female and male subjects, and between left and right eyes. However, subjects with astigmatism in one eye were likely to have it in the fellow eye (p < 0.001). A predominance of "against-the-rule" astigmatism was noted. PMID- 8508340 TI - Axonal loss in band atrophy of the optic nerve in craniopharyngioma: a quantitative analysis. AB - Automated image analysis was used to examine the optic nerves of a patient with previous craniopharyngioma and bitemporal hemianopsia. On histologic study the right optic nerve showed extensive damage, and the left optic nerve showed a band of damage horizontally across the nerve. Automated image analysis of the left nerve showed that the superior and inferior poles of the nerve had lost approximately 50% of their total nerve fibres, indicating that these areas contain a mixture of crossed and uncrossed fibres; the temporal portion showed a variable amount of loss. To our knowledge this is the first report illustrating quantitatively the pattern of axonal loss in this type of lesion. PMID- 8508341 TI - Congenital aplasia of the iris sphincter and dilator muscles. AB - Congenital aplasia of the iris sphincter and dilator muscles is rare. We describe a 3-month-old boy with a patent ductus arteriosus who had this anomaly, with no other ocular or systemic abnormalities. The child, whom we followed for over 7 years, had reduced accommodative amplitudes. This anomaly, although it bears some similarity to Gillespie's syndrome, circumpupillary aplasia and aniridia, is an isolated, nonprogressive condition that general physicians need to differentiate from the neurologically dilated pupil so that misdirected, unnecessary investigations can be avoided. PMID- 8508342 TI - Familial parafoveal telangiectasis. AB - We report two cases of parafoveal telangiectasis encountered in the same family. The patients are father and son. Both patients are healthy. Both presented with small parafoveal telangiectatic vessels, with minimal associated subretinal fluid. There were no other associated conditions. To the best of our knowledge these cases represent the first reported cases of father-to-son transmission of parafoveal telangiectasis. PMID- 8508343 TI - Cone-rod retinal dystrophy in a patient with neurofibromatosis type 1. PMID- 8508344 TI - Acute episode of asthma following topical administration of betaxolol eyedrops. PMID- 8508345 TI - Cyclosporine in the treatment of nonmicrobial inflammatory ophthalmic disease. PMID- 8508346 TI - Clinically localized prostatic carcinoma. PMID- 8508347 TI - Proliferative breast "disease". An unresolved diagnostic dilemma. PMID- 8508348 TI - Irradiation of carcinoma of the esophagus containing a tracheoesophageal fistula. AB - BACKGROUND: For patients with locally advanced esophageal carcinoma, tracheal involvement is common, and the formation of a tracheoesophageal fistula is a frequent complication of the disease, with or without treatment. However, the presence of a tracheoesophageal fistula has historically been considered a relative contraindication to radiation therapy. Therefore, we are presenting a case report whereby irradiation was continued despite the presence of such a fistula. METHODS: A 60-year-old white man diagnosed with Stage III, T4N0M0, moderately well-differentiated invasive squamous cell carcinoma of the esophagus was initially treated with four courses of chemotherapy (5-fluorouracil and cisplatin) and had an excellent tumor response. He was then referred for consolidative radiation therapy (XRT). At 600 cGy, he had symptoms consistent with a tracheoesophageal fistula (TEF), which was documented by barium swallow at 3000 cGy. Radiation treatments were continued, but at a reduced fraction size that was gradually increased over several days. RESULTS: Upon completion of the radiation therapy, the TEF persisted but had completely disappeared 2 months post XRT. However, at 4 months post-XRT, the fistula recurred due to tumor recurrence. At 6 months post-XRT, he died with metastatic disease, 16 months after initial diagnosis and 8.5 months after the first TEF occurred. CONCLUSIONS: The presence of a TEF may not be an absolute contraindication to radiation therapy. Radiation therapy may be initiated or continued in the presence of a TEF, and eventual resolution of the fistula may occur. Recurrence of a healed TEF may indicate recurrence of a tumor. PMID- 8508349 TI - A phase III randomized study of 5-fluorouracil and cisplatin versus 5 fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. AB - BACKGROUND: With the introduction of cisplatin-containing regimens in the treatment of advanced gastric cancer, promising clinical results have been reported. A 61.5% response rate was observed with a combination of 5-fluorouracil (5-FU) infusion and bolus cisplatin; however, the superiority of cisplatin containing regimens to other regimens has not been clearly verified in any randomized controlled studies. A prospective, randomized study of 5-FU and cisplatin (FP) versus 5-FU, doxorubicin, and mitomycin C (FAM) versus 5-FU alone (FU) in previously untreated patients with advanced gastric cancer is reported. METHODS: A total of 324 patients were entered into the trial and 295 patients (103 for FP, 98 for FAM, 94 for FU) were evaluable. The patients were randomized to receive FP, FAM, or FU after stratifying by the following factors: performance status, presence of measurable disease, and resection of the primary tumor. RESULTS: The overall response rate for patients with measurable disease in the FP arm was significantly higher than in the FAM and FU arms (51% for FP; 25% for FAM; 26% for FU). The durations of response for each arm, however, were not significantly different. Even though the median time to progression for the FP arm (21.8 weeks) was longer than that for the FAM arm (12 weeks; P < 0.05) and for the FU arm (9.1 weeks; P < 0.005), there was no statistical difference in overall survival among the three arms. Toxicity for all three regimens was moderate and consisted primarily of myelosuppression, nausea, vomiting, and alopecia. CONCLUSIONS: Although the FP regimen showed a significantly higher response rate and a longer time to progression than the FAM or FU regimens, a survival benefit was not observed. PMID- 8508350 TI - Variation in colorectal cancer incidence in the United States by subsite of origin. AB - BACKGROUND: Colorectal cancer incidence rates vary widely internationally, by race and gender, and have changed over time. Investigation of the patterns by subsite within the colorectum may suggest clues of possible etiologic significance for further study. METHODS: Using population-based data on more than 120,000 cases diagnosed 1976-1987 in the United States Surveillance, Epidemiology, and End Results program, colorectal cancer incidence was evaluated by subsite of origin. RESULTS: Little racial variation was evident for cecum and ascending colon cancers; rates were higher among blacks than whites for transverse and descending colon cancers but lower for sigmoid, rectosigmoid, and rectal cancers. Rates generally increased over time for most colon sites, especially sigmoid colon among white men, but declined slightly for rectal cancer among whites. The sex ratio increased among whites monotonically from 1.12 for cecum to 1.71 for rectal cancers. The distal colon cancer excess among men was most notable at older ages, contrasting with slightly higher rates among women at younger ages. Geographic differences were particularly notable for transverse and rectosigmoid colon cancers. CONCLUSIONS: It may be fruitful for future studies to evaluate factors affecting colorectal carcinogenesis by subsite of origin. PMID- 8508351 TI - Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type. AB - BACKGROUND: New measures enabling better prediction of biologic behavior of large bowel cancer are highly desirable. One hundred ninety-four consecutive primary, recurrent, and metastatic colorectal adenocarcinomas, accessioned during 1991 at Rhode Island Hospital, were classified according to the presence and specific type of K-ras-2 point mutation. METHODS: An integrated histopathologic-genetic approach was used to detect mutations starting with minute, topographically selected, tissue samples from formaldehyde-fixed, paraffin-embedded specimens. RESULTS: Each colorectal adenocarcinoma exhibited either no or only one of seven specific types of K-ras-2 mutation. The mutation type of each primary tumor was present consistently in its metastatic deposits. Thirty-five percent of primary colorectal adenocarcinomas were found to be mutated (42 of 119). A significantly higher mutation rate (65%) was seen in lymphogenous-hematogenous metastases as a group (35 of 54; P < 0.005). By contrast, 22% of anastomotic recurrences and transcoelomic metastasis were mutated (4 of 18). Twenty-eight percent of adenocarcinomas with invasion limited to muscularis propria (Tis, T1, T2) were mutated (16 of 57), compared to 41% for more deeply invasive tumors (T3, T4; 26 of 63). When colorectal adenocarcinomas were analyzed by specific K-ras-2 mutation type, it was found that codon 13 mutated tumors did not progress to local or distant metastasis (P < 0.01). Tumors having a codon 12 valine substitution did not metastasize beyond pericolonic-perirectal lymph nodes. In contrast, colorectal cancers with codon 12 aspartic acid substitutions accounted for most of the distant hematogenous deposits (P < 0.01). Tumors with normal K ras-2 accounted for most intraperitoneal deposits. CONCLUSIONS: Genotyping of colorectal adenocarcinoma by K-ras-2 status can identify subsets of patients likely to pursue indolent and aggressive forms of disease. The integrated histopathologic-genetic approach outlined is feasible for use in diagnostic pathology, providing information that together with clinicopathologic staging may individualize and optimize treatment. PMID- 8508352 TI - Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens. AB - BACKGROUND: The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. METHODS: DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin-embedded tumor tissues. RESULTS: An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, +/- 0.9) in comparison to 4.5 +/- 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. CONCLUSIONS: Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials. PMID- 8508353 TI - Prognosis of undetected intrapulmonary metastases in resected lung cancer. AB - BACKGROUND: Between 1975 and 1989, 839 patients with lung cancer underwent pulmonary resection at Okayama University Medical School; for this study data of the 42 (5.0%) who had intrapulmonary metastasis were analyzed. RESULTS: The 5 year survival rate for the 42 patients was 25.7%, which was significantly better than that of patients with Stage IV disease and extrapulmonary metastasis, none of whom survived for 3 years. The 2-year survival rate was found to be significantly better in patients with one-lobe metastasis (n = 37; 41.5%) than in those with two-lobe metastasis (n = 5; 20.0%). Adenocarcinoma was the most common tumor (66.8%), followed by squamous cell carcinoma (28.6%), but the prognosis differed little between these two histologic types. Intrapulmonary metastasis did not unfavorably affect the prognosis when the primary tumor was 3 cm or less in greatest dimension and there were no lymph node metastases (T1N0). CONCLUSION: In patients with lung cancer and one-lobe intrapulmonary metastasis, particularly in those with T1N0, a favorable prognosis can be expected after surgery. PMID- 8508354 TI - Dual-color flow cytometric analysis of megakaryocytic DNA ploidy in the investigation of blastic phase chronic myelogenous leukemia with rearrangement of 3q26. AB - A patient is described with chronic myelogenous leukemia in blastic crisis, in whom numerous circulating platelet fragments and megakaryocytic nuclei were present, with 50% blasts and 50% micromegakaryocytes in the marrow. The blasts expressed myeloid-associated antigens CD34, CD33, and CD13, whereas the micromegakaryocytes were positive for CD41, CD42b, and CD61. These findings suggested a myeloblastic transformation with a possible megakaryoblastic component. Cytogenetic analysis showed rearrangement of 3q26 in the form of t(2;3) (p13;q26), in addition to t(9;22) (q34;q11). Dual-color flow cytometric analysis of DNA content of CD42b-positive cells showed that the micromegakaryocytes were predominantly 2N, indicating a maturation block before nuclear endoreplication and polyploidization. These findings confirmed a combined myeloblastic and megakaryoblastic transformation. It is concluded that dual-color flow cytometric DNA analysis is a useful method for the investigation of abnormal megakaryocytopoiesis in hematologic malignancies. PMID- 8508355 TI - Randomized study of individualized induction therapy with or without vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 Study of the Japan Adult Leukemia Study Group. AB - BACKGROUND: It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance-intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). METHODS: A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance-intensification therapy was randomized to 4 or 12 courses given every 6 weeks. RESULTS: Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance-intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French-American-British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. CONCLUSIONS: Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML. PMID- 8508356 TI - Reproducibility and validity of pathologic classifications of benign breast disease and implications for clinical applications. AB - BACKGROUND: Research studies on the relationship between benign breast diseases and cancer risk typically identify certain conditions as risk factors, and others as carrying no prognostic significance. This study addresses several issues concerning the relevance of such research results for advising individual patients in a clinical setting. METHODS: Data were obtained as part of a "blinded" retrospective pathology review of benign breast biopsies. A random sample of cases was reviewed twice, providing information about reliability. Comparisons with diagnoses that used information from the operative reports and gross pathology descriptions as well as microscopic histology were used to assess validity. RESULTS: Among cases that were reviewed twice, excellent agreement was achieved for diagnosing carcinoma and lobular neoplasia, good agreement for adenosis and intraductal papilloma, and relatively poor agreement about levels of hyperplasia and atypia, and whether ducts or lobules were involved. Distinctions among levels of hyperplasia also apparently were influenced by the number of slides available for review. The "blinded" review diagnoses frequently differed from the diagnoses that used all information available at the time of surgery in detecting the presence or absence of gross cystic disease, and in distinguishing solitary from multiple papillomas. CONCLUSIONS: Problems with reliability of precise distinctions among levels and sites of hyperplasia and atypia seem to limit the usefulness of such classifications as guidelines for individual patient care. For conditions with some clinical manifestations, diagnoses based exclusively on histologic review of biopsy specimens often are not accurate. PMID- 8508357 TI - Tumor labeling indices of primary breast cancers and their regional lymph node metastases. AB - BACKGROUND: Tumor labeling index has emerged as a strong predictor of the clinical course of women with breast cancer. This study investigated whether labeling index of primary tumors correlates with labeling indices of concurrent regional node metastases. METHODS: With appropriate written consent, preoperative in vivo infusion of the thymidine analogue 5-bromodeoxyuridine (BrdUrd) was used to label 109 human breast cancers. Labeled S-phase cells were identified immunohistochemically with an antibody specific to DNA-incorporated BrdUrd. Labeling index was the fraction of labeled nuclei in 2000 tumor nuclei. For 30 women, there was sufficient cancer in axillary lymph nodes to compare labeling indices in primary breast cancer and regional lymph node metastases. RESULTS: The 30 women were from 25 to 82 years of age. Tumors were from 1 to 12 cm in size and there were from 1 to 26 positive nodes. Tumor labeling index ranged from 0.1% to 34%, (mean, 11.1%; median, 10.3%) and axillary lymph node metastasis labeling index ranged from 0.1% to 27.7% (mean, 10.8%; median, 10.0%). There was strong correlation between primary tumor labeling index and regional lymph node metastases labeling index (r = 0.82, with 95% confidence interval 0.65-0.91). The correlation persisted within subgroups according to age, tumor size, number of positive nodes, and hormone receptor status. Primary tumor and lymph node metastases labeling indices also had statistically similar relationships with age, level of hormone receptors, tumor size, and number of positive nodes. CONCLUSIONS: Primary tumor and regional node labeling indices correlate strongly; the relationship is not influenced by age, level of hormone receptors, tumor size, or number of positive nodes. PMID- 8508358 TI - Proliferation index as a prognostic marker in breast cancer. AB - BACKGROUND: The proliferative activity of tumors has been extensively investigated with different approaches, among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation. In this study, the proliferative activity of 129 primary breast cancers was investigated, and the results were related to prognosis. METHODS: Tumor samples, obtained from 129 patients who underwent surgery between January 1987 and December 1988, were processed for staining by an immunohistochemical procedure (avidin-biotin complex). The median time of observation was 42 months (range, 31-55 months). Life-table analysis (Mantel-Cox) was used to assess the probability of disease-free survival (DFS) and overall survival (OS). RESULTS: Tumors with high Ki-67 proliferation indices (> 20%) were associated with a higher 4-year probability of relapse of disease (55.3% versus 79.1%; P = 0.003) and death (71% versus 95.6%; P = 0.00005) when compared with tumors with low Ki 67 values. In addition, this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement, menopausal status, and nuclear estrogen receptor content. CONCLUSIONS: Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS. PMID- 8508359 TI - Clinical evaluation of 252Cf neutron intracavitary therapy for primary endometrial adenocarcinoma. AB - BACKGROUND: A pilot feasibility study of the neutron-emitting radioisotope 252Cf was done on patients with uterine adenocarcinoma and medically inoperable disease or unfavorable G3 histologic findings. METHODS: 252Cf intracavitary therapy was combined with 40-45 Gy of fractionated whole-pelvis photon therapy. In select patients, hysterectomy was performed. RESULTS: Thirty-one patients with Stage I III adenocarcinoma of the corpus uteri were treated with 252Cf neutron brachytherapy. The patients treated often were in poor general medical condition and had multiple chronic medical illnesses for which conventional radiation and surgery usually would not be recommended. 252Cf allowed short implant treatment time (hours), was usable in a small number of insertions (the average number of insertions was two), and was useful for treating large volume tumors. Stage and grade of the tumor were important determinants of patient survival. The 5-year actuarial survival was 83% for patients with Stage I disease but only 37% for those with Stage II disease (primarily adenosquamous cell carcinomas). The 5-year survival was 100% for patients with Grade 1 tumors, 88% for those with Grade 2 tumors, and 21% for those with Grade 3 tumors. CONCLUSION: 252Cf neutron brachytherapy was found to be an effective and well-tolerated therapy for endometrial carcinoma. The excellent therapeutic efficacy and good patient tolerance make it suitable for additional evaluation in future Phase II-III trials. PMID- 8508360 TI - DNA flow cytometric analysis of serous ovarian tumors of low malignant potential. AB - BACKGROUND: Ovarian serous tumors of low malignant potential (STLMP) occasionally progress; a small percentage of patients die of the tumor. There is no known way to predict which tumors will progress. METHODS: Forty STLMP were analyzed by DNA flow cytometry and compared with 26 serous carcinomas. RESULTS: Forty percent of Stage I STLMP and 40% of Stage III STLMP were DNA aneuploid as compared to 54% of serous carcinomas. Aneuploidy was found in 50% of STLMP that progressed and in 38% of neoplasms that did not progress. Four of the 30 Stage I STLMP progressed, and 3 of the 4 were aneuploid; whereas, of the 26 Stage I STLMP that did not progress, 9 were DNA aneuploid. Stage III STLMP were aneuploid in 4 out of 10 instances (40%). Aneuploidy was not related to progression as three of four DNA diploid tumors progressed, and three of six that did not progress were aneuploid. Thirteen of 16 aneuploid STLMP had peridiploid aneuploid populations. The mean follow-up periods were 14.3 years for Stage I STLMP and 8.3 years for Stage III STLMP: CONCLUSIONS: DNA aneuploidy in Stages I and III STLMP does not identify neoplasms likely to relapse with sufficient frequency to be useful in identifying those patients at high risk for relapse. PMID- 8508361 TI - Survival after transurethral and transvesical surgery in localized cancer of the prostate, Norway 1957-1981. AB - BACKGROUND: During the period 1957-1981, there has been a gradual change in the choice of surgical methods for patients with prostate cancer in Norway, from transvesical surgery to transurethral resections (TUR-P). Radical prostatectomy was practically nonexistent in the early years of this time period. Sixty-five percent (17,696 patients) of all patients with prostate cancer reported to the Cancer Registry had no metastases at the time of diagnosis. Of these, 5414 patients underwent TUR-P, whereas 6160 patients underwent transvesical operations as primary surgery. Interest was raised in analyzing survival after primary surgery. METHODS AND RESULTS: Five-year relative survival rates were calculated for the groups of patients undergoing each type of surgery; the rates increased steadily for both groups during the later years of the 1957-1981 period. However, survival consistently was better for patients who had transvesical surgery. The difference in 5-year relative survival rates was 10-15%. The same pattern was seen long-term survival (more than 10 years). In addition, survival rates for patients with similar grade of tumor differentiation were better for patients undergoing transvesical surgery. A multivariate analysis of survival that related age, surgical methods, grades of tumor differentiation, and diagnostic periods showed that survival was influenced most by differentiation, followed by surgery. Age was not an important factor in this analysis. CONCLUSION: The results underline the importance of additional research regarding the precise classification of prostatic cancer at the time of diagnosis so that clinicians can better choose the proper method of surgery. PMID- 8508362 TI - Extragonadal seminoma involving urinary bladder and arising in the prostate. AB - The authors report the first instance of a patient with seminoma probably arising from the prostate but also involving the bladder. A 58-year-old man presented with symptoms and signs of prostatic enlargement. Cystoscopy revealed a fungating neoplasm, probably arising from the prostate and surrounding the bladder neck. The biopsy was consistent with the diagnosis of seminoma. The patient experienced complete remission after chemotherapy with bleomycin, cisplatin, and etoposide. PMID- 8508363 TI - Cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of metastatic prostate cancer. A Southwest Oncology Group study. AB - BACKGROUND: Hormone-refractory metastatic prostate cancer remains a therapeutic challenge. Cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), a drug combination that is active in solid tumors, was evaluated using specific response criteria. METHODS: Fifty-two eligible patients with measurable (19), evaluable (29), or bone scan only (4) metastatic prostate cancer were treated with cyclophosphamide, 100 mg/m2 every day by mouth, methotrexate, 15 mg/m2 intravenously weekly, and 5-fluorouracil, 300 mg/m2 intravenously weekly. Treatment was given continuously unless interrupted by toxicity or disease progression. RESULTS: There were two partial responses (7%) among the evaluable patients. Six (32%) measurable patients and four (14%) evaluable patients had stable disease. Median time to progression was 3.2 months for measurable and 2.8 months for evaluable disease patients. Median survivals were 10.9 and 10.2 months, respectively. There was no difference between the two groups with regard to response rate or survival. Toxicity was acceptable and consisted primarily of myelosuppression. CONCLUSIONS: CMF is minimally active in hormone-refractory metastatic prostate cancer. PMID- 8508364 TI - Transitional cell carcinoma of the renal pelvis and ureter in Taiwan. DNA analysis by flow cytometry. AB - BACKGROUND: The incidence of upper urinary tract tumors is relatively high in southern Taiwan. DNA analysis by means of flow cytometry is not well investigated with regard to tumors of the upper urinary tract and the differences in DNA ploidy between transitional cell carcinomas in endemic and nonendemic areas. METHODS: A retrospective nuclear DNA ploidy analysis by flow cytometry comprised 41 formaldehyde solution-fixed, paraffin-embedded tissue specimens of transitional cell carcinoma of the renal pelvis and ureter. The preparation of nuclear suspensions from paraffin-embedded tissue blocks and staining were modified by means of the techniques of Hedley and Vindelov. RESULTS: There was no statistical correlation between DNA ploidy, histologic grade, and pathologic stage, however, 82% of the DNA nondiploid tumors showed tumor progression. In contrast, only 46% of the DNA diploid tumors revealed tumor progression. Among Grade 2 tumors, 85% of the DNA nondiploid tumors showed postoperative tumor progression, whereas only 31% of the DNA diploid tumors showed tumor progression. Seventy-nine percent of the nondiploid patterns were present in patients native to the Pa Chang Valley, where the so-called "blackfoot disease" and urothelium tumor are endemic, whereas only 22% appeared in patients living in other areas. CONCLUSIONS: DNA flow cytometry can identify a group of patients with poor outcome unpredictable by pathologic examination, and is an important tool in research into the pathogenesis of cancer. PMID- 8508365 TI - The value of pathologic factors in predicting cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate. AB - BACKGROUND: A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer-specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate. METHODS: Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer specific survival. RESULTS: Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival. CONCLUSIONS: If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials. PMID- 8508366 TI - Oligodendroglioma. The Princess Margaret Hospital experience (1958-1984). AB - BACKGROUND: Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone. METHODS: The medical records of 72 patients with the diagnosis of oligodendroglioma, registered at the Princess Margaret Hospital (PMH) between 1958 and 1984, were reviewed retrospectively. The data of 68 patients were evaluated, but 4 patients were excluded from the analysis because of inadequate follow-up. The median follow-up period at the time of analysis was 7.5 years. Tumors were classified as oligodendrogliomas, malignant oligodendrogliomas, or mixed oligoastrocytomas. Fifty-eight (85%) patients received postoperative irradiation at initial diagnosis, and 10 (15%) patients were treated with surgery alone. In most patients (76%), the radiation dose was 5000 cGy in 25 fractions given during a period of 5 weeks. RESULTS: Five- and 10 year overall survival was 66% and 30%, respectively. Forty-two (62.0%) patients experienced disease relapse during the follow-up period. The median time to relapse from initial diagnosis was 2.6 years. Most tumor recurrences were at the primary site. Two patients developed distant metastasis within the CNS axis. Histologic subtype was the only significant prognostic factor for survival. The patients with oligodendroglioma and malignant oligodendroglioma had 5-year survival rates of 73% and 32%, respectively (P = 0.033). CONCLUSIONS: The authors drew three conclusions. (1) Most patients eventually died with this tumor from local recurrence without distant metastasis. Local tumor control remains the major problem. (2) Tumor histologic subtype is a significant prognostic factor. (3) No statistically significant benefit can be attributed to postoperative irradiation; however, the number of patients not receiving radiation therapy was small (10). Thus, the role of radiation therapy remains a matter of controversy. PMID- 8508367 TI - Occult carcinoma of the thyroid. A systematic autopsy study from Spain of two series performed with two different methods. AB - BACKGROUND: Occult carcinoma of the thyroid (OCT) seems to be present in a significant proportion of the general population. Previous studies have shown large variations in the prevalence rate of OCT, which may be due to differences in the prevalence rates between different geographic areas, but also to the lack of standardized diagnostic criteria and methods of examination. The epidemiologic features of OCT at autopsy in Spain are reported for the first time. METHODS: To investigate the influence of methodology in the results, two series were studied, each one using a different method. In Series A, 625 cases were studied, and sections were taken only from grossly visible lesions. In Series B, the whole thyroid glands of 100 autopsies were cut into blocks and all blocks were histologically studied. In addition, immunocytochemical stainings were performed in Series B for calcitonin, thyroglobulin, and epidermal keratin. RESULTS: Series A found 33 OCTs (5.28%), consisting of 29 occult papillary carcinomas (OPC), 2 occult follicular carcinomas, 1 occult oxyphilic carcinoma, and 1 occult medullary carcinoma. Series B found 22 OPC cases (22%) containing a total of 53 tumor foci. Tumor diameter varied from 0.07 to 1.8 mm. The epithelial cells of all the OPC were negative for calcitonin, weakly positive for thyroglobulin, and intensely positive for epidermal keratin. One case had metastasis in a regional lymph node. CONCLUSIONS: This study shows that the differences in the incidence of OCT found in numerous studies are due not only to actual different geographic incidences but also to the method of study. PMID- 8508368 TI - Addisonian crisis as the presenting feature of bilateral primary adrenal lymphoma. AB - The authors report a patient with a primary lymphoma of the adrenal glands presenting as acute adrenal failure. Fine-needle aspiration biopsy of the adrenal glands revealed a non-Hodgkin lymphoma of predominantly small cleaved cells and a low degree of malignancy. The absence of abnormal findings in clinical, bone marrow, and computed tomography scan examinations supports the diagnosis of primary non-Hodgkin lymphoma of the adrenal glands. Chemotherapy produced a complete functional recovery, and tumoral masses disappeared after the first three cycles of treatment. PMID- 8508370 TI - Comparison of doubling times of serum carcinoembryonic antigen produced by various metastatic lesions in recurrent gastric and colorectal carcinomas. AB - The authors measured the serial serum carcinoembryonic antigen (CEA) levels in patients with recurrent gastric or colorectal carcinoma. Among the 45 patients with recurrent gastric carcinomas, those with lung metastases showed the most prolonged CEA doubling time (CEA-DT), followed by those with liver and peritoneal metastases, respectively. Of the 31 patients with recurrent colorectal carcinomas, those with local recurrence showed the most prolonged CEA-DT, followed by those with lung, liver, and peritoneal metastases, respectively. A positive correlation was observed for gastric and colorectal carcinomas between CEA-DT in patients with metastatic lesions and outcome (R = 0.84 and 0.93, respectively). The results of the current study suggest that postoperative measurement of CEA-DT is useful in the determination of region of recurrence of carcinoma, which would permit early surgery and chemotherapy. Measurement of CEA DT also may be helpful for the accurate determination of prognosis. PMID- 8508369 TI - Clinically silent progressive renal tubulointerstitial disease during cisplatin chemotherapy. AB - BACKGROUND: Chronic cisplatin nephrotoxicity is well documented in animal models but not well characterized in humans. The authors report a 56-year-old woman who had end-stage chronic tubulointerstitial nephropathy develop during treatment with multiple courses of cisplatin chemotherapy for ovarian carcinoma. METHODS: A biopsy was performed to determine the etiology of renal failure, and the morphologic, immunofluorescent, and ultrastructural findings were analyzed to identify possible causes, other than cisplatin, of chronic renal disease. RESULTS: Morphologic studies showed extensive renal tubulointerstitial fibrosis with relative sparing of glomeruli. CONCLUSIONS: Profound, progressive renal injury occurred during cisplatin treatment despite adherence to treatment protocols designed to minimize such toxicity. Renal injury was undetected by pretreatment serum creatinine determinations. This case and others emphasize the relative insensitivity of this test for chronic renal damage during treatment with nephrotoxic drugs. PMID- 8508371 TI - Combined carboplatin and cisplatin. Limited prospects for dose intensification. AB - BACKGROUND: The relative lack of overlapping toxicities and less-than-complete cross-resistance of tumors treated with both carboplatin and cisplatin may allow these two analogues to be given in combination to exploit platinum dose intensity therapeutics. Early experience with combined platinum regimens, however, found myelosuppression, particularly severe thrombocytopenia, to be dose-limiting. It was postulated that a 2-day interval between carboplatin and cisplatin would allow for near complete clearance of the former before cisplatin administration and a potential gain in dose intensity. METHODS: Other carboplatin-cisplatin regimens produced Grade 3-4 toxicity in 20% of patients. By defining 95% confidence limits around this observed rate of Grade 3-4 toxicity, the accrual needs of this study were determined in a two-stage process. Sixteen patients with advanced malignancies were entered onto a trial of 300 mg/m2 of carboplatin on day 1, followed by 125 mg/m2 of cisplatin on day 3 every 28 days. Hematologic and nonhematologic toxicity was closely monitored, including the use of serial audiograms, to allow appropriate dose modification. RESULTS: A total of 40 courses of combination platinum therapy was administered to 15 patients who were evaluable for toxicity. Higher-than-anticipated ototoxicity and neurosensory toxicity was observed. WHO Grade 3 ototoxicity (hearing loss) was documented in 12 of 15 patients (80.0%, 95% confidence interval [CI]: 52.0-97.0%) and emerged as the dose-limiting side effect of this regimen. High-frequency hearing loss, as demonstrated by conventional audiograms, was universal among all 12 patients who received at least 2 courses of combination platinum therapy (100%, 95% CI: 73.5 100%). Grade 2 or 3 neurosensory toxicity also was observed in 4 of 15 patients. Hematologic toxicity was manageable. WHO Grade 3-4 neutropenia or thrombocytopenia occurred in only 14% and 11%, respectively, of 40 courses. There was no evidence of cumulative marrow toxicity. Calculated dose intensities (mg/m2/week) were 94 +/- 26.0 for carboplatin, 39.3 +/- 12.4 for cisplatin, and 64.0 +/- 19.2 for the combination (expressed as cisplatin equivalents). Objective responses (complete response+partial response) occurred in 8 of 16 subjects (50.0%, 95% CI: 24.7-75.4%), with 1 patient achieving a complete response of 14+months. CONCLUSIONS: The schedule of day 1 carboplatin plus day 3 cisplatin every 4 weeks appeared to allow a higher platinum dose intensity with less myelotoxicity than previously reported schedules combining these two analogues. Ototoxicity, however, was unexpectedly severe and limits future prospects for the use of combined platinum analogues to achieve dose intensification. PMID- 8508372 TI - Intrapleural immunotherapy with escalating doses of interleukin-2 in metastatic pleural effusions. AB - BACKGROUND: The authors assessed the tolerance and efficacy of intrapleural interleukin-2 (IL-2) in patients with malignant effusion. METHODS: Twenty-three patients had a total of 25 metastatic pleural effusions; the patients were treated with recombinant IL-2 by means of a continuous intrapleural infusion for 5 days. The daily dosage used in this Phase I/II trial initially was 3 x 10(6) IU/m2/day; the dosage was increased with every third patient, culminating in a dosage of 24 x 10(6) IU/m2/day. RESULTS: One patient who had received the highest dosage died of renal failure on day 8. Ninety-six percent of patients had Grade 2 3 fever, which was easily controlled with paracetamol administration. Two (8%) patients had pleural empyema. All other side effects were mild and resolved spontaneously by the end of treatment. The objective response rate was 21.7%. The five patients who responded to IL-2 therapy were alive 7-24 months after treatment, and the survival rate of the whole group was 59% after 13 months. CONCLUSION: A daily dose of 10-24 x 10(6) IU/m2/day of IL-2 administered intrapleurally gave response rates similar to those reported in the literature using the intravenous route, but a much lower morbidity rate was recorded. PMID- 8508373 TI - Treatment-related esophageal stricture in pediatric patients with cancer. AB - BACKGROUND: Intensive antineoplastic regimens have enhanced long-term survival in pediatric patients with cancer, but can result in long-term complications. Esophageal stricture formation is one such complication. METHODS: We reviewed the experience with benign esophageal stricture in pediatric patients with cancer over the past 15 years in a major cancer center. Clinical course, along with endoscopic, radiologic, and manometric esophageal studies, was reviewed. RESULTS: Esophageal strictures formed in five pediatric patients who were treated with radiation and/or chemotherapy. Stricture formation was associated with abnormal esophageal motility in four out of the five patients. Repeated esophageal dilation was performed from 3-50 times and resulted in stricture resolution in only 2 of the 5 patients. CONCLUSIONS: Esophageal stricture formation in this population is rare, but is associated with long-term morbidity. PMID- 8508374 TI - Childhood intracranial meningiomas after high-dose irradiation. AB - BACKGROUND: Irradiation, either alone or in association with other factors, is thought to play a role in the causation of intracranial meningioma. METHODS: The authors report two 15-year-old patients with convexity meningiomas as a result of high-dose irradiation received at a young age and review the English language literature reports of 13 pediatric patients with meningiomas after high-dose irradiation. The clinical characteristics of the 15 patients are presented. RESULTS: There were nine girls and six boys. The mean age at the time of irradiation was 2.5 years (2 months-9 years), and the mean age at diagnosis of meningioma was 13 years (5-15.5 years). The mean radiation dose was 4154 cGy (1500-8000 cGy). In 11 of the 15 patients, the meningioma was located in the calvarial area. Only 1 of 15 had multiple tumors, and only two of the tumors were clearly malignant at diagnosis. In ten patients, gross total resection was recorded, and two patients underwent subtotal resection. Three died of recurrent/disseminated meningiomas. CONCLUSIONS: This study suggests that meningiomas after high-dose radiation in children are mostly calvarial in location, rarely multiple, mostly benign in histologic type, and that complete removal is possible in most patients. The age at the time of radiation is young (mean age, 2.5 years) and the latent period is short (mean, 10.8 years). Although the clinical course of radiation-induced meningiomas in childhood generally is benign, high doses of radiation at a young age are to be avoided, and other means of therapy should be used if possible. PMID- 8508375 TI - Malignant melanoma in childhood. AB - Six cases of malignant melanoma in children 14 years of age and younger are reported. The six cases were diagnosed among 850,000 consecutive skin biopsy specimens and consultation slides examined within a 32-year period. This series included an infant born with neurocutaneous melanosis, a child with malignant melanoma developing in a large congenital nevus at the age of 13 years, a superficial spreading malignant melanoma, Clark Level III, in a child with many dysplastic nevi, and three cases with primary nodular malignant melanoma, two of which showed histologic features of Spitz nevus. A review of the literature indicates that malignant melanoma in childhood is rare, and no large series have been investigated. It is not known whether the genetic and the environmental factors incriminated in the development of malignant melanoma in adults play a role in childhood melanomas. Data on the incidence of childhood melanoma in the population, the clinical and the histologic variations, and the prognosis are not adequate. A multiinstitutional study is needed to gather a large enough series to provide this information. PMID- 8508376 TI - Fatal brain stem necrosis after standard posterior fossa radiation and aggressive chemotherapy for metastatic medulloblastoma. AB - A 3-year-old girl received conventional-dose external beam posterior fossa irradiation (5400 cGy in 30 fractions over 40 days) for good-risk medulloblastoma. Soon thereafter, she experienced an extraneural (occipital scar, cervical lymph nodes) and central nervous system (CNS) recurrence. Intensive cisplatin and cyclophosphamide chemotherapy led to rapid disappearance of the extraneural disease. Methotrexate was administered via a ventricular reservoir. After 2 months of chemotherapy, CNS toxicity progressed rapidly from ataxia to paraplegia to quadriplegia to central respiratory failure. Radiographic scans and autopsy material revealed brain stem necrosis. This unusual toxicity raises concern about the safety of aggressive systemic chemotherapy and intrathecal therapy, when given after conventional radiotherapy. PMID- 8508377 TI - The biology of colorectal cancer. Implications for pretreatment and follow-up management. AB - The biology of colorectal cancer is discussed in terms of multistage carcinogenesis. Colorectal cancer evolves through the stepwise acquisition of mutations at certain critical genetic loci, many of which have been identified recently. The earliest step in the neoplastic pathway is a shift of proliferation from the normally restricted zone at the base of the colonic crypt and the retention of cells capable of proliferation at the top of the colonic crypt. This appears to be mediated by a mutation in the APC gene. The adenoma, a collection of benign neoplastic cells, is the first pathologically recognizable neoplastic lesion. Adenomas may grow or involute. Additional genetic lesions, such as a mutation in the Ki-ras gene, contribute to the growth and progressive dysplasia of the adenoma. Critical lesions in the p53 gene appear to be responsible for malignant transformation and the appearance of genetic instability of the neoplastic cell, which greatly increases the likelihood that additional genetic events will occur that contribute to a progressively more aggressive neoplastic phenotype. Genetic and phenotypic diversity develop within the primary malignant tumor, and metastasis occurs as a consequence of a complex series of events. Opportunities for detection and therapeutic intervention in colorectal neoplasia are discussed in this framework. PMID- 8508378 TI - Colon and rectum cancer. Patterns of spread and implications for workup. AB - The preoperative evaluation of patients diagnosed as having colon or rectum cancer is influenced by the anatomic location of the primary tumors; the knowledge that 10-25% of patients harbor detectable metastases at time of initial diagnosis; the observation that as many as one-third of patients with isolated metastases may achieve significant survival benefit by aggressive surgery; and the need to accurately stage low rectum cancers to permit selection of appropriate surgery. Patients are evaluated by colonoscopy, air-contrast barium enema when required, computed tomography, and serum carcinoembryonic antigen. Magnetic resonance imaging, especially of the pelvis, may be useful, and endorectal ultrasound has an important role in staging low rectum cancer. A thorough preoperative evaluation is essential in selecting appropriate operative therapy and for sequencing surgery with available adjuvant treatments. PMID- 8508379 TI - Relevant clinical information and tumor markers. AB - The preoperative clinical assessment of patients with colorectal cancer provides the surgeon with sufficient information to allow an accurate assessment of operative risks, to plan the extent of resection needed to remove the primary and any associated synchronous lesions, to determine whether perioperative care should be modified to enhance the safety of the proposed surgery (bowel preparation, ureteral catheters, or ostomy placement), to determine operability and probable intent of surgery (curative or palliative), and to determine whether additional, more sophisticated testing is needed to better stage the disease to determine prognosis and ideal treatment. The surgeon, through the process of informed consent, must properly balance these patient and disease factors to select and plan the appropriate treatment that maximizes the potential for cure while minimizing morbidity and mortality. PMID- 8508380 TI - Radiology and endoscopy in the pretreatment diagnostic management of colorectal cancer. AB - This paper discusses the imaging methods available for the detection and diagnosis of colon cancer, concentrating on endoscopy and barium radiology. Effective utilization of these two methods may be facilitated by using flexible sigmoidoscopy to direct further investigation. There is a need for educational efforts to enhance the performance of endoscopy and barium radiology so that the high standards achieved in some published series are more generally available to patients. New developments in contrast agents will alter rapidly the roles of ultrasound, CT scanning, and magnetic resonance in the investigation and management of colorectal cancer. PMID- 8508381 TI - New staging techniques. Endoscopic ultrasound. AB - Rectal ultrasonography allows detailed images of rectal tumors and provides the most accurate method of staging rectal cancer. Ultrasound assessment of the extent of tumor invasion and lymph node involvement is superior to computed tomography (CT) scan, though CT is still the best method to assess liver involvement. Ultrasound assessment of cancers above the peritoneal reflection is less useful clinically because it currently does not alter management. Outcome studies have not been reported using ultrasound to stage rectal cancer but should be forthcoming. Inflammation present at the leading edge of the tumor is the greatest cause for overstaging, and difficulty in determining tumor involvement into, but not through, the muscularis propria is another important cause of inaccurate staging. Lymph node assessment can be problematic, but future developments in ultrasound-guided fine-needle aspiration cytology holds promise for more accurate assessment of lymph node status. Surgery will remain the standard method to treat rectal cancer, but new methods, such as high-intensity focused ultrasound, may provide new ways to treat some patients. PMID- 8508382 TI - New radiographic techniques for colorectal cancer. AB - Before surgical staging and resection, patients with primary colorectal cancer undergo a thorough diagnostic evaluation. The initial imaging study to identify a primary site of disease often is endoscopy, which frequently is supplemented with a double contrast barium enema. Once the presence of colorectal cancer has been established, new radiographic imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), and special ultrasound (US) may be used. Clinical questions addressed by these special imaging techniques include detection of liver and lymph metastases and clarification of local extent of disease. PMID- 8508383 TI - Immunoscintigraphy in primary colorectal cancer. AB - Immunoscintigraphy is an experimental diagnostic nuclear medicine imaging technique that targets tumor sites with radiolabeled antibodies reactive with tumor-associated antigens. Primary tumors, regional lymph node metastases, and distant metastases have been imaged in patients with colorectal cancer, and United States Food and Drug Administration (FDA) approval of a commercial preparation of radiolabeled murine monoclonal antibodies for diagnostic use in such patients is expected soon. Immunoscintigraphy is complementary to computed tomography (CT) scanning in the evaluation of the abdomen and pelvis in patients with colorectal cancer, and it has the additional capability of serial whole body imaging for detection of distant metastases. However, the clinical utility of immunoscintigraphy is being investigated, and its precise diagnostic role in patients with primary colorectal cancer has not been adequately defined. The management of selected patients at increased risk of regional or distant spread of tumor likely would benefit from detection of occult disease and a change in clinical staging, but the routine use of immunoscintigraphy in the preoperative evaluation of patients with primary colorectal cancer is more problematic. More studies are required to determine whether it should be used to stage all patients before operation or merely be reserved for selected patients at increased risk for metastatic disease. PMID- 8508384 TI - Standard postoperative monitoring of patients after primary resection of colon and rectum cancer. AB - The goal of monitoring after primary treatment of any solid tumor, including colon and rectum carcinoma, is to help the patient. The general parameters include prevention of secondary tumors or precancers (because most patients with solid tumors are at greater risk than the general population for second tumors of the same histology), the cure of symptomatic or asymptomatic tumor recurrences, and the palliation of symptomatic tumor recurrences. Additional rationale for more stringent follow-up is somewhat dependent upon the venue of patient care, including the necessity for more frequent studies if the patient happens to be in a protocol in which disease-free survival and/or patterns of recurrence are being investigated. Keeping these parameters in mind, most prevalent follow-up plans remain empiric and probably are not justifiable, on the basis of either cost effective analysis or real benefit to the patient. PMID- 8508385 TI - New imaging modalities for follow-up of colorectal carcinoma. AB - Recurrent disease after curative resection occurred in 37-44% of patients. The common sites of recurrent disease are at the anastomotic site, in the liver, in the lymph nodes, and in the peritoneal linings. Computed tomography (CT), barium enema, and endoscopy detected local recurrent disease in 61-88% of the patients, whereas magnetic resonance imaging (MRI) detected 80-88% of the cases reported in some Phase 1 studies. CT and MRI are equally effective in the detection of hepatic metastases when lesions are larger than 2 cm, with detectability rate of 95-100%. They are fair (50-60% detectability rate) when tumors are between 1 and 2 cm and poor (less than 40%) when tumors are smaller than 1 cm. For recurrent nodal metastases and peritoneal deposits, CT is the modality of choice. PMID- 8508386 TI - In-111 CYT-103 monoclonal antibody imaging in patients with suspected recurrent colorectal cancer. AB - Recurrent colorectal cancer is seen in as many as 40% of patients after curative resection. In view of the limitations of endoscopic and cross-sectional imaging, external immunoscintigraphy has been added to the follow-up regimen of patients at high-risk of recurrent disease. The authors investigated the utility of immunoscintigraphy with Indium-111 (In-111) CYT-103 (site specifically labeled conjugate of monoclonal antibody B72.3) in 19 patients with suspected recurrences after previous curative resection of colorectal carcinoma. Local or regional recurrences (4 patients) and liver metastasis (6 patients) were indicated by physical examination and computed tomography (CT), whereas nine patients had occult disease with increasing serum carcinoembryonic antigen (CEA) levels and negative conventional workups. Serum CEA levels were elevated (mean, 22 ng/ml) in all patients. Approximately 4.3 mCi In-111 labeled to 1.0 mg CYT-103 was administered intravenously to each patient. Planar and single photon emission computed tomography (SPECT) imaging were performed 2-5 days after infusion. The final diagnosis of recurrence or metastasis was established in 18 patients by second-look surgery or biopsy. One patient died before exploration. Tumor was identified at the following locations: pelvis (12 patients), abdominal wall (2 patients), retroperitoneum (1 patient), liver (5 patients), and omentum (2 patients). Superiority of monoclonal antibody (MoAb) scan is noted in the detection of pelvic and intraabdominal recurrences (100%) versus CT scan (43%). Liver metastases were identified with equal facility by both modalities. In-111 CYT-103 scan findings influenced the management of 10 (55%) of 18 patients. Surgery was avoided in one patient with disseminated metastases detected by the scan. Correct identification of occult local recurrences was made in six patients. An isolated liver metastasis was confirmed in one patient with equivocal CT scan. Finally, additional intraabdominal lesions were detected in two patients. These results suggest an important and beneficial role for In-111 CYT-103 MoAb imaging in patients with suspected recurrent colorectal carcinomas, particularly in patients in whom cross-sectional imaging is negative; such imaging may prevent patients from undergoing unnecessary surgical exploration. PMID- 8508387 TI - Pitfalls in antibody imaging in colorectal cancer. AB - Monoclonal antibodies against tumor-associated antigens can be conjugated to radionuclides and used to localize tumors in vivo. This technique may be useful in identifying recurrent disease that cannot be demonstrated using conventional studies such as computerized tomography. The literature suggests that the use of antibody fragments and SPECT imaging will increase the diagnostic yield. The choice of radionuclide may vary depending on the region of interest. Factors that influence the success of imaging include the experience of individuals interpreting the scan and the level of tissue antigen expression. Antibodies of murine origin may produce a human antimouse antibody response after imaging, causing allergic responses, interference with subsequent imaging or results of standard in vitro laboratory tests. Finally, false-positive images occur in more than 10% of patients. Current studies in patients with colorectal cancer should focus on determining if changes in management resulting from antibody imaging have a positive effect on either patient survival or quality of life. PMID- 8508388 TI - Surgical treatment of liver metastases in patients with colorectal cancer. AB - The incidence of colorectal cancer in the United States is increasing. Because more than half of patients with colorectal cancer have liver metastases develop, the number of patients with hepatic metastases also is increasing. Unfortunately, metastatic disease will be limited to the liver in perhaps 25% of these patients and confined to only one lobe of the liver 25% of this subgroup. Consequently, solitary or unilobar colorectal metastases are found in as few as 5% of patients with colorectal cancer. The median survival of patients with unresected hepatic metastases is approximately 10.6 months. Patients with solitary lesions or small tumor burdens may attain a median survival of 16-20 months, but 5-year survivors are extremely rare. In contrast, rates of 5-year survival average approximately 36% after resections of solitary hepatic lesions and may approach the same level in selected patients with multiple lesions. Factors that appear to adversely effect survival include detection of metastatic disease because of signs or symptoms of disease, an elevated carcinoembryonic antigen (CEA) level, elevated liver function tests, poorly differentiated primary lesions, lymph node-positive primary lesions, extrahepatic sites of metastases, more than four hepatic lesions, bilobar disease, a satellite pattern of metastases in the liver, positive margins of the liver resection, positive extrahepatic lymph nodes, and more than 10 units of blood transfusion during the perioperative period. Operative mortality for liver resections should remain approximately 4%, and major morbidity should be in the range of 20-30%. Modalities other than surgical resection have not improved survival in patients with colorectal hepatic metastases. Thus, when feasible, patients with metastatic colorectal cancer limited to one lobe of the liver should undergo hepatic resection. Unfortunately, only approximately 5% of patients with colorectal cancer fall into this category, so resection of hepatic metastases can improve overall survival of patients with colorectal cancer by only 1-2%. PMID- 8508389 TI - Results of surgical treatment of nonhepatic recurrence of colorectal carcinoma. AB - The sites of first recurrence of colorectal cancer include liver (more than 30%), lung and locoregional disease (20-25%), other intraabdominal sites (15-20%), and elsewhere (10%). Isolated locoregional disease accounts for 5-19% of colon recurrences and 7-33% of rectal recurrences. Between 7% and 20% of locally recurrent colorectal cancer can be resected with curative intent. Overall, complete resection of a localized recurrence yields a mean survival of 33-59 months, with long-term survival achieved in 30-50% of patients. Regional recurrence of rectal cancer may require abdominal-sacral resection for adequate margins, with 5-year survival of 18-24%. Early identification (by close monitoring) and accurate staging of recurrence are essential for potentially curative resection. Long-term survival depends on extent of recurrence and completeness of resection. Symptomatic recurrence to the ovaries that requires reoperation occurs in approximately 2% of patients; presentation usually is as part of a diffuse intraabdominal process, and resection is rarely curative. Isolated pulmonary metastases occur in 2-4% of patients experiencing disease recurrence; such tumors are resectable in half of the patients. After the tumors are surgically resected, long-term survival can be expected in 30-40% of patients, with prognosis variably associated with disease-free interval, number and size of lung metastases, and location and stage of the primary tumor. Newer techniques of postoperative monitoring after resection of the primary lesion, more sensitive preoperative and intraoperative staging of recurrences, and the use of intraoperative radiation therapy may increase surgical salvage of recurrent colorectal cancer. PMID- 8508390 TI - Nonsurgical management of recurrent colorectal cancer. AB - Most patients with colorectal carcinoma undergo attempts at curative surgery. However, some present with metastatic disease and many others ultimately relapse. Most recurrences of colorectal cancer are not resectable and require nonsurgical approaches such as chemotherapy and radiation therapy directed against local recurrences, hepatic metastases, and widely disseminated disease. Nonsurgical therapy for locoregional recurrence of rectal cancer can offer significant palliation. Intraarterial chemotherapy for liver metastases increases the likelihood of response compared to systemic treatments, but has little effect on survival. Extrahepatic progression and hepatic toxicity are important limitations to this regional therapy. 5-fluorouracil (5-FU) is the mainstay of systemic chemotherapy, and efforts to modulate biochemically the cytotoxic effects of 5-FU with folinic acid, phosphonacetyl-L-aspartate, interferon, and other agents have resulted in promising response rates. The different approaches to biochemical modulation are being studied in ongoing cooperative group trials. Novel approaches, including monoclonal antibody therapy, biologic modifier therapy, and gene therapy, are under investigation. PMID- 8508391 TI - The decision to treat patients with recurrent colorectal cancer. AB - Although universally performed, postoperative diagnostic screening in patients with colorectal cancer has not been demonstrated to diminish overall mortality. Such screening often leads to second-look surgery, with many anecdotal successes but again no evidence that overall mortality is reduced. The cost of such interventions is at least $1 billion dollars per year in the United States and may be twice that amount. The research that is needed to support postoperative screening and surgery is feasible and economically easily justified. The endpoints must be shifted from that of previous studies, which have focused on sensitivity of screening techniques, to mortality. Such a study is ongoing in Denmark, and early results of that study should be reported soon. PMID- 8508392 TI - Radioimmunodetection of solid tumors. Future horizons and applications for radioimmunotherapy. AB - Seventeen years after the development of hybridoma technology, the clinical utility of radioimmunodetection of solid tumors using monoclonal antibody-based imaging agents has been definitively established. As expected, these first immunoscintigraphy agents demonstrate certain limitations (most notably, suboptimal tumor-to-background radiolocalization ratios and immunogenicity), suggesting that the full potential of this technology has not been realized. This article reviews research strategies for optimizing the imaging performance of radiolabeled monoclonal antibodies. Promising approaches include the development of humanized tumor-targeting vehicles, improved chelator technology to link the antibody and the radioisotope, the use of smaller immunoreactive targeting agents, modifications of the tumor or host determinants of antibody biodistribution, regional delivery of immunoscintigraphic agents, use of antibody "cocktails," and advances in image acquisition technology. The successful application of these strategies should lead to improved agents for tumor radioimmunodetection. The results of these research efforts should be useful in developing radiolabeled monoclonal antibody-based agents for solid tumor therapy. PMID- 8508393 TI - Growth factor regulation by tamoxifen is demonstrated in patients with breast cancer. PMID- 8508394 TI - Recurrent non-0:1 Vibrio cholerae bacteremia in a patient with multiple myeloma. AB - BACKGROUND: Episodes of bacteremia with non-0:1 Vibrio cholerae are rarely reported, even though the organism is endemic along the Gulf Coast of the United States. Recurrent episodes of bacteremia with non-0:1 V. cholerae are described even more rarely. A patient is reported who had multiple myeloma and experienced two episodes of bacteremia with non-0:1 V. cholerae. METHODS: Hospital records and the medical literature were reviewed, and the organism was serotyped by the Alabama State Laboratory. RESULTS: The patient had no prodromal illnesses or diarrhea with either episode of bacteremia. Treatment with empiric antibiotic therapy resulted in successful resolution of his bacteremia, which is fatal in almost 50% of reported cases in patients with malignant neoplasms. CONCLUSIONS: This is the first reported case of non-0:1 V. cholerae bacteremia occurring in a patient with multiple myeloma. Both his initial episode and a second episode of bacteremia responded to broad-spectrum antibiotics, which are used as empiric therapy for patients with hematologic malignancies and fever. Emphasis is placed on the paucity of clinical manifestations and the need for empiric therapy for non-0:1 V. cholerae infection in patients with hematologic malignancies. PMID- 8508395 TI - Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma. AB - BACKGROUND: The analysis of peripheral blood mononuclear cells for plasma cells and B-cell surface light chain ratios may provide additional insight on the pathogenesis of multiple myeloma and predict disease activity. The goals of this study were to correlate these parameters with clinically determined disease activity and establish a cutoff value of circulating plasma cells that could be used in future clinical trials. METHODS: Peripheral blood samples from 84 patients with monoclonal gammopathies were analyzed by an immunofluorescence, slide-based, labeling index (LI) technique for detection of plasma cells, the LI, and light chain ratios. These parameters were compared with disease activity. RESULTS: Of the 84 patients studied, 27% had inactive and 73% had active disease. The mean number of plasma cells for patients with inactive disease was 0.61 x 10(6)/l, compared with 139.6 x 10(6)/l for patients with active disease (P < 0.001). The mean ratios of involved to uninvolved light chain percentages for patients with inactive and active disease were 1.6 and 9.2, respectively (P = 0.002). The absolute number of plasma cells better predicted disease activity than the light chain ratio. By use of a cutoff value of 3 x 10(6)/l, 67% of patients with active disease were determined to have 3 x 10(6)/l or more plasma cells, and 96% of those with inactive disease had less than 3 x 10(6)/l plasma cells. CONCLUSIONS: These results suggest that detection of circulating plasma cells is a marker of disease activity in patients with plasma cell disorders and that an appropriate cutoff value is 3 x 10(6)/l or more circulating plasma cells. PMID- 8508396 TI - Familial breast cancer risks. Effects of prostate and other cancers. AB - BACKGROUND: Previous studies have provided conflicting results concerning the effects of a family history of prostate and other cancers on breast cancer risks. METHODS: Three groups of families were studied to determine the effects of a family history of prostate cancer on breast cancer risks. Also considered were the effects of a family history of melanoma, colon, lung, ovarian, and endometrial cancers. Included were 422 first-degree female relatives of 114 patients with bilateral breast cancer, 320 first-degree relatives of 88 male patients with breast cancer, and 633 relatives of 186 unselected female patients. For estimating relative risks, observed numbers of breast cancers in relatives were compared with expected numbers based on population incidence data. Multiple logistic-regression also provided odds ratios of relatives affected with breast cancer. RESULTS: A family history of prostate cancer increased the breast cancer risks in each of the groups, compared with families without prostate cancer. Ovarian cancer in a family increased the breast cancer risks only in the bilateral breast cancer group, and endometrial cancer increased the risks in the bilateral and unselected groups. These increases in risk appeared to be the consequence of families with multiple cancers, including those with hereditary breast-ovarian cancers and the cancer family syndrome. A family history of melanoma, lung, or colon cancer did not increase breast cancer risks. CONCLUSIONS: A family history of prostate cancer, as well as endometrial and ovarian cancer, significantly increases the risk of breast cancer. PMID- 8508397 TI - Down-regulation of transforming growth factor-alpha by tamoxifen in human breast cancer. AB - BACKGROUND: The influence of tamoxifen treatment on transforming growth factor alpha (TGF-alpha) levels in human breast cancer rarely has been studied in vivo. METHODS: Postmenopausal patients with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive primary breast cancer underwent two fine needle aspiration biopsies (FNA) of the tumors. Between the two FNAs, 10 patients received no treatment (control group), and the other 10 patients received tamoxifen (20 mg/day) for 10 (8-12) days (TAM group). TGF-alpha levels in FNA samples were assayed by enzyme immunoassay. RESULTS: No significant difference was found in TGF-alpha levels between the first and second FNA samples in the control group. On the other hand, in the TAM group, TGF-alpha levels in the second FNA samples (2.5 +/- 0.5; mean +/- SEM ng/mg.DNA) were significantly (P < 0.01) lower than those in the first (4.5 +/- 0.8). Studies on the influence of tamoxifen treatment on TGF-alpha levels in ER-negative and PR-negative breast cancer showed that TGF-alpha levels were not affected by tamoxifen treatment. Positivity of epidermal growth factor receptor (EGFR) was 60% in ER-negative and PR-negative breast cancer and 30% in ER-positive and PR-positive breast cancer. CONCLUSIONS: Tamoxifen downregulates TGF-alpha levels in ER-positive and PR positive breast cancers through ER. The significance of TGF-alpha as an autocrine growth factor appears to be more important in ER-negative and PR-negative breast cancer with high EGFR positivity than in ER-positive and PR-positive breast cancer with low EGFR positivity. PMID- 8508398 TI - Vulvar melanoma reconsidered. AB - BACKGROUND: Melanoma of the vulva has traditionally been treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy. Cutaneous nonvulvar melanoma has been successfully treated with local excision with selective therapeutic regional node dissection. METHODS: A retrospective analysis of 16 patients with primary malignant melanoma of the vulva who underwent surgery from 1973 to 1988 at Indiana University Hospital was conducted. The purpose of this analysis was to determine if less radical surgery, such as that performed for cutaneous nonvulvar melanoma, might be adopted for patients with vulvar melanoma without compromising 5-year survival results. RESULTS: Surgical therapy included radical vulvectomy with bilateral inguinofemoral lymphadenectomy (n = 11), radical vulvectomy alone (n = 1), and wide local excision (n = 4). Treated International Federation of Gynecology and Obstetrics (1971) stages included I (n = 12), II (n = 3), and III (n = 1). The median age of the patients was 59 years (range, 29-79 years). The median depth of invasion according to the Breslow method was 3 mm (range, 0.1-8 mm). Patients were observed for a median of 24 months (range, 3-143 months). The Kaplan-Meier 5-year survival estimate was 30%. There were nine recurrences: five distant, one central, one nodal, and two mixed. A median depth of 0.9 mm (range, 0.1-1.75 mm) was noted in those who remained disease-free versus 4.6 mm (range, 3-8 mm) in those who experienced a recurrence (P < 0.01). None of the patients with lesion depths of 1.75 mm or smaller experienced a recurrence, whereas all of those with lesion depths larger than 1.75 mm suffered a recurrence (P = 0.0004). CONCLUSIONS: Patients with lesion depths of 1.75 mm or smaller may be treated with wide local excision. Patients with greater lesion depths are at high risk for the development of distant metastases. The patients with well-lateralized lesions may be equally well served with a less morbid procedure deferring therapeutic node dissection until there is a regional recurrence. PMID- 8508400 TI - p53CM1 expression is not associated with prognosis in uterine cervical carcinoma. AB - BACKGROUND AND METHODS: Specimens obtained from 192 patients with Stage III squamous cell carcinoma of the cervix treated by radiation therapy alone were investigated with an immunohistochemical method for the expression of p53CM1, a monoclonal antibody that recognizes wild and mutant type p53 gene products in histologic materials fixed and processed conventionally. RESULTS: Cancer cells that had positive results for p53CM1 showed a nuclear staining pattern. Of the 192 patients, 99 had tumors that had negative findings (-) for p53CM1, 44 had tumors that were weakly reactive or ambiguous (+/-), 36 had tumors with positive results (+), and 13 had strongly reactive tumors (++). There was no significant correlation between survival of patients and p53CM1 (-) or (+/-) expression or p53CM1 (+) or (++) expression (chi-square test and Kaplan-Meier method, P = 0.466). CONCLUSIONS: The p53CM1 expression in cancer cells is not a predictive factor for the prognosis of patients with cervical carcinoma. PMID- 8508399 TI - Tn antigen, a marker of potential for metastasis of uterine cervix cancer cells. AB - BACKGROUND: The expressions of Thomsen-Friedenreich antigen (T-Ag) and Tn antigen (Tn-Ag), precursors of MN blood group antigens, were examined in the tissues of squamous cell carcinoma of the uterine cervix from 111 patients to determine their clinicopathologic significance with regard to the biologic behaviors of cancer cells and the clinical course of the patients. METHODS: T-Ag and Tn-Ag were measured by the avidin-biotin-peroxidase (ABC) method with peanut (Arachis hypogaea) lectin (PNA) and Vicia villosa agglutinin (VVA), respectively. RESULTS: Unlike expression of T-Ag, that of Tn-Ag was correlated closely with vascular permeation of cancer cells, their parametrial spread and metastasis to the pelvic lymph nodes, and also with a low 5-year survival rate. No correlation was found between expression of Tn-Ag and other parameters, such as the clinical stage or histologic type. Furthermore, Tn-Ag expression was independent of the degree of cancer involvement in the fibromuscular stroma of the cervix, which seems to be a marker of the aggressiveness of cancer cell proliferation. CONCLUSIONS: These results indicate that Tn-Ag expression is a useful indicator of the potential for metastatic potential of cancer cells. Thus, a combination of estimations of the degree of cancer involvement in the cervical stroma and Tn-Ag expression seems the most useful for predicting the prognosis of patients with cervical cancer. PMID- 8508401 TI - Ploidy disturbances as an early indicator of intrinsic malignancy in endometrial carcinoma. AB - BACKGROUND: The need for a postoperative treatment of patients with highly aggressive endometrial cancer necessitates more specific and accurate prognostic indicators. METHODS: In a prospective study, 88 samples from 72 endometrial tumors were subjected to microfluorometric single-cell DNA analysis to assess the DNA content of the main stemline and the ploidy distribution histogram. The histologic grade of differentiation, architecture, and mitotic index (MI) also were evaluated as biologic characteristics of neoplastic cells. RESULTS: The main stemline was peridiploid in 44 of 72 cases, peritetraploid in 4 of 72, and aneuploid in 24 of 72. High ploidy levels (> 3 c) were associated strictly with papillary and solid architecture, high MI, and undifferentiated grade. Multiple analyses of different sites showed stable ploidy values in 11 of 13 cases; 2 solid tumors changed from showing peridiploidy to peritetraploidy in one of the three sites examined. The number of S-phase and greater than G2 cells (heteroploid index) was compared with MI and showed six tumors with histogram irregularities probably resulting from intratumor genetic instability. Survival information was available for 65 patients with a mean observation period of 50 months. A single parameter, high ploidy level (> 3 c), was the most important determinant of survival at all stages; its prognostic value was fundamental in patients with Stage I disease, in whom DNA content showed higher independent significance (P < 0.001) than the other histologic and clinical factors considered. CONCLUSIONS: These studies suggest that DNA content is a biologic characteristic firmly associated with tumor aggressiveness; DNA analysis could offer early and objective evidence of an intrinsic highly malignant phenotype. PMID- 8508402 TI - Carcinoma of the esophagus and tylosis. A lethal genetic combination. AB - Hyperkeratosis of the palms and soles (tylosis) is an uncommon genetic disorder. A small number of English families, however, have been described in which it is associated with carcinoma of the esophagus. The current report is of the first American family described with this condition. Members of those families affected with tylosis have at least a 90% risk of esophageal carcinoma by age 65 years. The paired conditions have an autosomal dominant mode of transmission and probably are controlled at a single genetic locus. The actual pathologic state might be mediated through an increase in epidermal growth factor receptors in the abnormal tissues. PMID- 8508403 TI - Is there an altered steroid profile in patients with endometrial carcinoma? AB - BACKGROUND: Besides the well-known association between endometrial carcinoma (EC) and unopposed estrogen, androgens also may play a role in this respect; however, previous studies on endogenous estrogens and androgens in patients with EC and control subjects have yielded mostly divergent results, probably because of the use of poorly defined control groups. METHODS: Circulating steroid and pituitary hormones and sex hormone-binding globulin were measured in patients with EC and matched control groups of either patients with nonmalignant postmenopausal bleeding (hospital control subjects) and healthy, symptom-free women (nonhospital control subjects). RESULTS: Patients with EC had higher serum levels of adrenal C21 and C19 steroids, estrogens, and biologically active testosterone than nonhospital control subjects, whereas the hospital control subjects constituted an intermediate group in this respect. CONCLUSIONS: The results clearly indicate an altered steroid homeostasis, probably reflecting an increased "adrenal drive" in patients with EC. The results also stress the necessity of using strictly defined, healthy, symptom-free control subjects instead of the frequently used hospital control subjects when studying more subtile endocrine aberrations. PMID- 8508404 TI - Image cytometric DNA analysis in transitional cell carcinoma of the bladder. AB - BACKGROUND: The current study was initiated to investigate measurable objective and reproducible characteristics that might have prognostic significance in bladder cancer. METHODS: Tumor samples from 91 patients with primary transitional cell carcinoma (TCC) of the urinary bladder were studied by DNA image cytometry and cytogenetic analysis. Image cytometry is a more sensitive method of determining ploidy than flow cytometry, especially in tumors with a low number of aneuploid cells. RESULTS: There was a significant difference in survival between DNA image cytometry-determined diploid and nondiploid cases. The presence of nuclei with a high DNA content indicated poor prognosis. The 2C deviation index (2CDI) also was an indicator of survival. Image cytometry-determined factors also were found to be strong predictors of progression-free survival. In multivariate analysis, 2CDI was the only cytometric parameter with an independent but weak correlation with survival. In multivariate analysis, none of the cytometric parameters had an important contribution to prediction of progression-free survival. In superficial tumors (Ta and T1), 2CDI appeared to be the most important independent predictor of survival. With respect to progression-free survival, tumors with a high mitotic index proved to have a worse prognosis. CONCLUSIONS: Parameters determined by DNA image cytometry appear to be valuable in predicting survival and progression-free survival and may be useful in addition to the classic parameters of stage and grade, especially in superficial TCC. PMID- 8508405 TI - Supratentorial low-grade astrocytoma. Correlation of computed tomography findings with effect of radiation therapy and prognostic variables. AB - BACKGROUND: In supratentorial low-grade astrocytoma, radiation therapy effects and prognostic factors, especially with respect to computed tomography (CT) findings, are not yet well established. A retrospective analysis of 119 patients with this disease (histologically confirmed ordinary astrocytoma) therefore was conducted. METHODS: Between 1965 and 1989, 101 patients received postoperative radiation therapy, whereas 18 patients received surgery alone. Radiation was directed to the tumor plus a 1- to 3-cm margin in almost all cases; the dose range was 41 to 66 Gy (mean, 57 Gy). CT scan was performed before treatment on 74 patients. Postoperative survival rates were compared by both univariate and multivariate analyses. RESULTS: The 5- and 10-year survival rates for the irradiated group were 60% and 41%, respectively, which were significantly better than those for the surgery-alone group (37% and 11%, P = 0.048). Among various potential prognostic factors for the irradiated patients, only a lower age was associated with a better prognosis. Sex, tumor site (deep-seated or not), extent of surgery, radiation dose and field, and adjuvant chemotherapy did not influence the prognosis significantly. Among various CT findings, a clear tumor margin, a maximum tumor area less than 25 cm2, presence of a cyst, and lack of mass effect were associated with a better prognosis on univariate analysis (P = 0.02-0.12), but contrast enhancement was not related to prognosis. On multivariate analysis, however, mass effect was the only significant factor. CONCLUSIONS: Radiation therapy appears definitely to be effective in improving the prognosis for low grade astrocytoma. Younger age, and the absence of mass effect determined by CT, were associated significantly with a better prognosis. PMID- 8508406 TI - Familial clusters of nasopharyngeal carcinoma and salivary gland carcinomas in Greenland natives. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) and anaplastic salivary gland carcinoma (SGC), both associated with Epstein-Barr virus (EBV), are common among Inuit from Greenland, Canada, and Alaska. Because immigrant studies have shown that factors acting early in life are important for the development of NPC, the authors interviewed new patients in Greenland with either NPC or SGC about their lifestyles during childhood and additional cases in their families. METHODS: On admission, new patients from Greenland with either NPC or SGC were interviewed about childhood life-style, family size, and other cases of NPC or SGC within the family. Additional cases were confirmed by review of the medical records concerning these patients. RESULTS: During the 11 years from 1980 through 1990, 17 of 63 (27%) cases in Greenland were found in familial clusters among first degree relatives. There were no differences in the life-styles of multiple-case families and single-case families. CONCLUSIONS: The high rate of familial clusters among natives of Greenland is of interest because EBV is believed to play a role in the origin of these two diseases similar to that of Marek disease in neurolymphomatosis of chickens. Therefore, the familial clustering of NPC and SGC may indicate that an enhanced oncogenic potential of an EBV strain may occur more frequently in Greenland than in other parts of the world. PMID- 8508407 TI - Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy. AB - BACKGROUND: Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus. METHODS: All patients had surgery performed in a single thoracic surgical unit at the Tata Memorial Hospital between January, 1984 and December, 1987. The clinicopathologic factors studied were (1) gross residual disease at operation; (2) morphology of the tumor; (3) depth of microscopic invasion; (4) lymph node involvement; (5) histologic grade; (6) vascular and lymphatic embolism; and (7) sex. DNA ploidy and S-phase fraction (SpF) were determined by flow cytometry on archival tissues extracted from paraffin blocks. Ploidy status could be determined successfully in all 74 tumors, whereas SpF could be assessed only in 25. RESULTS: Of the various prognostic factors examined with the Cox stepwise regression model, residual disease (P = 0.000), depth of invasion (P = 0.047), and lymph node status (P = 0.077) were found to be correlated with overall survival. CONCLUSIONS: DNA ploidy was not related to prognosis. The overall survival of this group of patients at 36 months was 28%, and median survival was 18 months. PMID- 8508409 TI - Myelodysplastic syndrome after cisplatin therapy. AB - Therapy-related myelodysplastic syndrome (tMDS) and acute nonlymphocytic leukemia (tANLL) are known late complications of cytotoxic drug therapy for hematologic malignancies, solid tumors, and nonmalignant conditions. The alkylating agents are often the causative agents, but a few reports have implicated cisplatin as an etiologic agent. Cisplatin has a significant impact on the treatment of a number of malignant neoplasms, including testicular and ovarian cancer, and is a part of several clinical trials for squamous cell carcinoma of the head and neck region. Given its increasing use, a complication as significant as tMDS is potentially important. In this article, the authors describe the case of a patient who had myelodysplastic syndrome develop after successful treatment for laryngeal cancer with cisplatin. The treatment included cisplatin in combination with 5 fluorouracil, followed by radiation therapy. The authors also present a review of articles in the literature regarding tMDS and tANLL occurrence after treatment with cisplatin-containing regimens. The authors conclude that cisplatin can be a leukemogenic agent. The drug may potentiate the leukemogenic effects of other alkylating agents and drugs that inhibit topoisomerase II action. PMID- 8508408 TI - Serum levels of soluble interleukin-2 receptor in Hodgkin disease. Relationship with clinical stage, tumor burden, and treatment outcome. AB - BACKGROUND: Previous studies suggested a possible role for the detection of soluble interleukin-2 receptor (sIL-2R) in Hodgkin disease (HD). In this study, the authors investigated, in a large series of patients, sIL-2R serum levels in relation to disease features at presentation and prognosis. Their usefulness as markers in the management of individual cases was evaluated. METHODS: The sIL-2R serum levels were measured in 195 patients at diagnosis. In 72 of these patients, sIL-2R serum levels were also monitored after diagnosis. An additional 87 cases were tested only in complete remission (CR), and 25 were tested only at relapse. RESULTS: The sIL-2R levels at diagnosis were increased (mean +/- 1222 +/- 1012 versus 331 +/- 145 U/ml in controls, P < 0.0001) and correlated with the stage and tumor burden (Stages I and II = 1058 +/- 1007, Stages III and IV = 1502 +/- 942 U/ml, P = 0.003; Stage A = 954 +/- 705, Stage B = 1880 +/- 1238 U/ml, P < 0.0001; bulky presentation = 1958 +/- 1430, nonbulky presentation = 1043 +/- 791 U/ml, P < 0.0001). Response to treatment was associated with progressive reduction of sIL-2R levels, which were normal in virtually all cases 1 year after CR. Significantly greater levels at diagnosis were found in 11 patients who experienced a poor response or progression after treatment (P = 0.004). Overall, abnormal data in CR were found in 59 of 159 patients and 9 of them subsequently experienced a relapse. CONCLUSIONS: The sIL-2R serum levels in HD correlate with features at presentation and subsequent clinical courses. Higher levels at diagnosis entail a significantly higher risk of treatment failure. PMID- 8508410 TI - Increased risk of cancer in patients with Gaucher disease. AB - BACKGROUND: An increased incidence of cancer, especially hematopoietic in origin, has long been suspected but never established in patients with Gaucher disease. METHODS: To determine whether patients with Gaucher disease have an increased risk of cancer, the authors conducted a retrospective cohort study, comparing the incidence and type of cancer in 48 patients with Gaucher disease with those of 511 control subjects without the disease. RESULTS: Among patients with Gaucher disease, 10 of 48 (20.8%) had cancer, as compared with 35 of 511 (6.8%) of the control group (P = 0.0027; relative risk, 3.6; 95% confidence interval, 1.7-7.5). As compared with the control group, patients with Gaucher disease had a 14.7-fold risk of having cancer of hematopoietic origin (10.4% [5 of 48] versus 0.78% [4 of 511], respectively; P = 0.00037; 95% confidence interval, 5.2-41.7). The mean age at cancer diagnosis in the group with Gaucher disease was 57 +/- 18 years. CONCLUSIONS: The authors conclude that patients with Gaucher disease have a significantly increased risk of cancer, occurring in late adulthood. Of all the cancers, hematologic cancers are significantly more prevalent. PMID- 8508411 TI - Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines. AB - BACKGROUND: The antihelminthic drug levamisole (LMS) is used in conjunction with 5-fluorouracil (5-FU) as adjuvant therapy to reduce the incidence of colon cancer relapse following surgical resection. Clinical trials in patients with breast cancer have yielded conflicting results as to its efficacy in the treatment of this malignancy. LMS is thought to act as an immunostimulant, yet its precise mechanism remains unclear. In this study, the effect of LMS on major histocompatibility complex (MHC) class I (MHC I) and MHC class II (MHC II) expressions in human colorectal and breast carcinoma cell lines was examined. METHODS: The colon cancer cell line CaCo-2 and the breast cancer cell line MDA-MB 435 were cultured for 24-68 hours in the presence or absence of 10-microns LMS followed by staining with antibodies directed against either MHC I or MHC II: After staining, cells were visualized by fluorescent microscopy. RESULTS: When cultured in the presence of LMS, cells from both cell lines exhibited a decreased fluorescent intensity with antibodies directed against MHC I protein. The most significant difference from cells cultured without LMS was apparent after 48 hours of incubation. Neither cell line exhibited fluorescent intensities above background when stained with anti-MHC II antibody. CONCLUSIONS: LMS decreases the expression of MHC I on CaCo-2 and MDA-MB-435 tumor cell lines. Prior studies have indicated that natural killer (NK) cells are more efficient in attacking cells with lowered or no MHC I expression. An MHC I deficiency induced by LMS would augment NK-mediated immune surveillance. One mechanism contributing to levamisole's anti-tumor activity in vivo may be reduction of MHC I expression on tumor cells. PMID- 8508412 TI - bcl-2 rearrangements in de novo diffuse large cell lymphoma. Association with distinctive clinical features. AB - BACKGROUND: The frequency and clinical significance of bcl-2 rearrangement in de novo B-cell diffuse large cell lymphoma is largely unknown. METHODS: Using Southern blot hybridization and multiple DNA probes, the status of the protooncogene bcl-2 was investigated in frozen tissue samples from 45 carefully selected cases of de novo diffuse large cell lymphoma of B-cell origin. Results were correlated with the presenting clinical and immunophenotypic features and with the subsequent clinical course. RESULTS: Rearrangements of bcl-2 were identified in nine tumor specimens (20%). The bcl-2-positive cases more often presented as early-stage, nonmucosal associated extranodal tumors (P = 0.06) and were more often HLA-DR negative (P = 0.07). Five-year failure-free survival was poor among the bcl-2-positive cases (11% versus 48%). Overall survival was no different, however, because relapses in bcl-2-positive cases tended to be responsive to further therapy. CONCLUSIONS: Analysis of bcl-2 rearrangements in de novo diffuse large cell lymphoma may identify a subset of patients with unusual clinical features. PMID- 8508413 TI - Single-agent carboplatinum for advanced seminoma. A phase II study. AB - BACKGROUND: To reduce the side effects of cisplatin-based combination chemotherapy, the activity of carboplatinum was evaluated in patients with advanced seminoma. METHODS: Forty-two evaluable patients with advanced seminoma (defined as abdominal lymph nodes > 5 cm or supradiaphragmatic or visceral disease) received single-agent carboplatinum at a dose of 400 mg/m2 intravenously every 4 weeks for a maximum of six cycles. The median follow-up was 31 months (18 67 months). RESULTS: Thirty patients (71%) achieved a complete remission (CR; 21 chemotherapy alone, 9 with additional surgery), 8 patients (19%) a partial remission (PR), and 4 patients had disease progression (10%). Patients with metastases confined to the lymph nodes had a significantly higher remission rate than patients with visceral metastases (97% versus 50%; P < 0.002). Elevation of lactate dehydrogenase or human chorionic gonadotropin before radiation therapy had no influence on response rate. Eight patients have relapsed (five from CR and three from PR). All 12 patients failing carboplatinum therapy received cisplatin based combination regimens. Ten patients achieved a stable favorable response (eight CR, two PR), whereas two patients died of their disease. Currently, 30 patients (71%) are continuously free from progression (25 CR, 5 PR), and 40 patients are alive (survival 93%). Toxicity was mild with no neurotoxicity or nephrotoxicity. CONCLUSIONS: The use of up-front carboplatinum therapy appears not to compromise the ultimate curability of patients with advanced seminoma. Randomized trials, however, will have to demonstrate the effectiveness of carboplatinum with regard to survival, and help to identify prognostic subgroups of patients who require up-front cisplatinum-based combination chemotherapy. PMID- 8508414 TI - Influence of radiologically and cytologically assessed distant metastases on the survival of patients with esophageal and gastroesophageal junction carcinoma. The Rotterdam Esophageal Tumor Study Group. AB - BACKGROUND: Distant metastasis in carcinoma of the esophagus and gastroesophageal junction is associated with a poor survival after resection. To improve the selection of patients for surgical and nonsurgical treatment, this study determined the influence on survival of distant metastases, as assessed on radiologic studies or proven on cytologic studies. METHODS: During the period 1989-1990, 135 patients were referred to the institution in this study. On ultrasonographic or computed tomographic studies, distant metastases were suspected in 62 patients and were absent in 73 patients. In 33 patients, metastases were proven cytologically; 32 of these patients subsequently were excluded from surgery. Twelve other patients were unfit for surgery because of their general condition. The remaining 91 patients had surgery; 77 patients had transhiatal esophagectomy, and the tumor was unresectable in 14 patients. RESULTS: The 2-year survival rate for all patients in whom distant metastases were suspected on radiologic studies was 11.2%, and it was 44.3% for patients without metastases on these studies (P < 0.001). For patients with cytologically proven metastases, the 2-year survival rate (3%) was lower than for patients in whom distant metastases were suspected on radiologic studies but not cytologically confirmed (21.1%) (P < 0.001). There was no statistically significant difference in survival between this last group of patients and those without metastases identified by radiologic studies (P = 0.87). After resection, the 2-year survival rate decreased from 53.9% to 0% when distant metastases were present on histopathologic studies of the resected specimen (P = 0.04), and there was no significant difference in survival between patients with distant metastases suspected or absent on preoperative radiologic studies (P = 0.47). CONCLUSIONS: Surgery should be avoided in patients with cytologically proven distant metastases because the expected survival rate is low and surgery does not seem to be a life-prolonging procedure in these patients; however, patients should not be excluded from surgery on the basis of metastases identified by radiologic studies alone. PMID- 8508415 TI - Hypercalcemia complicating childhood malignancies. AB - BACKGROUND: Hypercalcemia complicating malignancy is a frequent complication in adults, but little has been published about the pathogenesis or the true incidence of hypercalcemia in children with cancer. METHODS: Hypercalcemia developing in childhood malignancies was studied retrospectively at St. Jude Children's Research Hospital to determine its incidence, the timing of its presentation, and its response to therapy. RESULTS: Over a 29-year period, 25 children (median age, 9.5 years) had been diagnosed and treated for hypercalcemia that occurred during the course of their malignancy. These 25 represented 0.4% of the total number of children treated for cancer at the institution during that period. Their malignancies comprised acute leukemias (11; 0.6%), rhabdomyosarcoma (4; 1.2%), malignant rhabdoid tumor (2), Hodgkin disease (1), non-Hodgkin lymphoma (1), hepatoblastoma (2), neuroblastoma (1), brain tumor (1), angiosarcoma (1), and a solid malignant tumor of undetermined type. CONCLUSIONS: Patients with acute lymphoblastic leukemia were more likely to present with hypercalcemia at the time of their initial diagnosis and to achieve resolution of this complication, whereas patients with solid tumors presented with hypercalcemia later in the course of their disease and had hypercalcemia that was more resistant to therapy. In contrast to adults with cancer, hypercalcemia of malignancy is extremely rare in children. PMID- 8508416 TI - Central nervous system treatment in childhood acute lymphoblastic leukemia. Long term follow-up of patients diagnosed between 1973 and 1985. AB - BACKGROUND: Despite advances in the treatment of childhood acute lymphoblastic leukemia (ALL), optimal therapy of the central nervous system (CNS) remains controversial. METHODS: Between 1973 and 1985, 540 children with ALL (199 standard risk and 341 high risk) were treated on four protocols. RESULTS: The 7 year event-free survival rate (+/- standard error) was 62.1% (+/- 2.1) for the entire group: 71.8% (+/- 3.2) for standard-risk and 56.4% (+/- 2.7) for high-risk patients. Five hundred eighteen of the children entered complete remission and received cranial irradiation with intrathecal methotrexate for CNS treatment; 197 had standard-risk ALL and 321 had high-risk ALL. Thirty-one patients (5 standard risk and 26 high risk) had a CNS relapse with or without concurrent bone marrow relapse as an initial event, the latest of which was observed 49 months after complete remission. The cumulative incidence of CNS relapse was 6.0% (+/- 1.1) for the entire group: 2.5% (+/- 1.1) for standard-risk and 8.2% (+/- 1.5) for high-risk patients (P = 0.01). CNS recurrence of leukemia, whether as an "isolated" site or a "combined" site of relapse, was a major adverse event. Only 4 of 31 patients were alive for 25+, 28+, 54+, and 71+ months after a CNS relapse. The median survival time after CNS relapse was 22 months: 21 months for the 20 patients who had an isolated CNS relapse, and 23 months for the 11 patients who had a CNS relapse concurrent with a recurrence in other sites. CONCLUSIONS: Although attempts to diminish CNS treatment-related morbidity are warranted for standard-risk patients, the authors recommend that intensive CNS treatment be enhanced for the high-risk patients because CNS relapses continue to occur in this population. Furthermore, CNS relapse after cranial irradiation was associated with a very poor prognosis and needs to be treated as intensively as a bone marrow relapse. PMID- 8508417 TI - A phase II evaluation of thiotepa in pediatric central nervous system malignancies. AB - BACKGROUND: Both thiotepa and its active metabolite, tepa, efficiently cross the blood-brain barrier. After intravenous administration, the cerebrospinal fluid concentrations achieved are nearly identical to those in plasma. This provides a strong rationale for testing this agent against brain tumors. METHODS: Sixty pediatric patients with recurrent primary brain tumors were treated on a multiinstitutional Phase II study of intravenous thiotepa at a dose of 65 mg/m2 administered every 3 weeks. This dose is the result of a prior pediatric Phase I trial and is significantly higher than those previously recommended. RESULTS: Three of 13 assessable patients with medulloblastoma had partial responses lasting 22, 25, and 54 weeks. Although no objective responses were observed in 16 assessable patients with malignant gliomas and 14 with brain stem gliomas, 5 of 16 and 4 of 14 patients in these respective strata had prolonged periods of stable disease (SD) lasting from 12 to more than 33 weeks. Nine assessable patients with ependymoma had no objective response, but two had SD, both for more than 33 weeks. Myelosuppression was the principle toxic effect encountered and appeared to be more severe in patients who had received prior craniospinal radiation therapy or nitrosourea therapy. CONCLUSIONS: By conventional Phase II criteria, thiotepa appears to have activity in medulloblastoma. Based on several patients with prolonged SD, it also may possess some limited activity in brain stem and malignant gliomas. The steep in vitro dose-response curve of thiotepa and the long durations of response or SD observed with the dose reported here suggest that moderate-dose to high-dose thiotepa with cytokine support or autologous bone marrow rescue may be associated with an improved response rate to this agent. PMID- 8508418 TI - Impaired muscle strength in female adolescents and young adults surviving leukemia in childhood. AB - BACKGROUND: With the improving cure rate in childhood malignancies, increasing interest has been focused on long-term survivors. To evaluate late sequelae of childhood leukemia, the muscle strength of 43 young female survivors was investigated and compared with that of 69 healthy age-matched women. The patients had been off therapy for 1 to 19 years. METHODS: The anthropometric characteristics measured were height and weight, and body mass index was calculated. The maximal isometric strengths for elbow flexion, knee extension, and hand grip were measured on a special dynamometer chair. Dynamic muscular endurance was measured by pushup and situp tests. RESULTS: The mean height of the patients was 6.5 cm shorter (P < 0.001) and their mean weight 4.8 kg lighter (P = 0.011) than that of the reference subjects. Muscle strength was in most tests poorer in the patients than in the reference subjects. The differences were statistically significant in elbow flexion and knee extension, and in both muscular endurance tests. There was an association between the maximal isometric strengths and the anthropometric characteristics. Even when allowance was made for the smaller size of the patients, however, they still had less muscle strength than the reference subjects. Of the various treatment modalities, radiation therapy to the cranial area and chemotherapy with L-asparaginase were independently associated with the lower muscle strength values. CONCLUSIONS: The muscle strength of female patients may be subnormal for many years after therapy for childhood leukemia. To compensate for these deficiencies, the possible benefits of prophylactic and individually planned exercise should be studied. PMID- 8508419 TI - An increased relative frequency of retinoblastoma at a rural regional referral hospital in Miraj, Maharashtra, India. AB - BACKGROUND: Retinoblastoma is a relatively uncommon childhood malignant neoplasm. It has been suggested previously that there is an increased incidence of retinoblastoma in India, but this has been reported primarily from urban cancer centers and may have been confounded by a referral bias. METHODS: The authors have evaluated the relative frequency of tumors in children younger than 15 years of age from 1987 to 1990 at Wanless Hospital, a rural regional referral hospital in India. RESULTS: Of 158 children with malignant neoplasms, 13% (20) had the histologically confirmed diagnosis of retinoblastoma. Assuming that these 158 children represent a nonbiased reflection of childhood cancer incidence in this region, these 20 cases of retinoblastoma blastoma represent a 3.3-fold increase over the expected number estimated with worldwide relative frequencies and a 4.4 fold increase over the relative frequency expected among a similar group of children as estimated with United States rates. The proportion of children with bilateral disease was 15%, which is less than expected (20-30%). The mean age at presentation was 41 +/- 14 months (mean +/- standard deviation) compared with 26 months in Western centers. In addition, 50% had metastases at the time of diagnosis compared with 5-10% at Western centers. The increased rate of metastases and late age at diagnosis suggest of a diagnostic delay. CONCLUSIONS: These results, in combination with previously reported increased relative frequencies from urban cancer centers in India, suggest that there may be a true increase in the incidence of retinoblastoma in India. The increase in unilateral retinoblastoma indicates that environmental factors may contribute to an increase of the nonheritable form in India. PMID- 8508420 TI - Thermoradiation therapy for superficial malignant tumors. AB - BACKGROUND: Between 1980-1990, 126 patients were treated with radiation therapy (RT) and hyperthermia using 915-MHz external microwave applicators. All but 11 patients had failed to respond to previous therapy. METHODS: The mean tumor volume was 73 +/- 13 cm3, and the mean radiation dose delivered was 45 +/- 1 Gy. Hyperthermia was administered biweekly in 83% of the fields in 5.5 +/- 0.2 sessions. Lesions were stratified by depth. The predictive influence of pretreatment or treatment parameters was analyzed for the probability of response by logistic regression and for the duration of local control by proportional hazards. RESULTS: In tumors considered potentially heatable (i.e., < or = 3-cm deep), the complete response (CR) rate was 70%, whereas the CR rate for patients with tumors deeper than 3 cm was 18% (P < 0.0001). Among superficial lesions of less than or equal to 3-cm depth that exhibited a CR, 14 recurred (26%, 8.7 +/- 1.6 months), while 39 lesions were recurrence-free at last follow-up of 17.8 +/- 1.4 months. The 50% tumor-effective dose was 44 Gy. For superficial lesions that received between 30-60 Gy, the CR rate was 55% when the fraction size was less than 3 Gy, whereas it was 77% when the fraction size was 3-4 Gy (P = 0.05). Multivariate logistic regression analysis indicated that the model best correlating with CR included concurrent radiation dose (P = 0.006) and tumor volume (P = 0.02; model P = 0.0001). Multivariate proportional hazard analysis indicated that the model best correlating with duration of local control included tumor histology (P = 0.004; model P = 0.0007). The overall survival rate of patients with lesions of less than or equal to 3-cm depth who were treated with thermoradiation therapy was 16.1 +/- 1.2 months. For patients with lesions more than 3-cm deep, survival was 8.7 +/- 1.1 months (P < 0.001). Forty-two fields were treated without any skin reactions (33%), 59 exhibited erythema (47%), and 25 experienced thermal blistering (20%). CONCLUSIONS: Treatment of superficial malignant tumors can benefit from the adjuvant use of hyperthermia delivered with external 915-MHz applicators provided tumors are less than 3 cm from the surface and the lateral margins are within the 50% specific absorption rate (SAR) on the surface. PMID- 8508421 TI - Epidemiology of lymphomatoid papulosis. PMID- 8508422 TI - Syndrome of inappropriate secretion of antidiuretic hormone in a patient with carcinoma of the nasopharynx. PMID- 8508423 TI - Optimal treatment for advanced seminoma? PMID- 8508424 TI - Peculiar nuclear clearing composed of microfilaments in papillary carcinoma of the thyroid. PMID- 8508425 TI - Peripheral T-cell lymphoma involving the placenta. PMID- 8508426 TI - Microvascular architecture of early gastric carcinoma. Microvascular histopathologic correlates. AB - BACKGROUND: Gastric carcinoma is clinicopathologically divided into differentiated and undifferentiated types. The former is grossly protuberant and often causes hematogenous metastasis to the liver or lung, whereas the latter is mostly depressed or ulcerated from its early stage and rarely causes blood-borne metastasis. The purpose of this study is to clarify the microvascular architecture of early gastric carcinoma with reference to the histologic subtypes. METHODS: A silicone rubber compound (Microfil) injection method with a methyl salicylate clearing technique was used in 32 resected early gastric carcinomas. The microvascular architecture was observed both in the carcinoma and its surrounding noncancerous tissue in each specimen under a stereomicroscope and light microscope. RESULTS: Compared to the surrounding normal mucosa, the differentiated carcinomas (DC) mostly were hypervascular (24%) or normovascular (65%), whereas the undifferentiated carcinomas (UC) often were hypovascular (60%). Irregularity of tumor vessels (67%) and an arcade-like appearance (33%) was encountered frequently in UC, whereas hypervascularity of the surrounding noncancerous mucosa (29%) often was noticed in DC. Quantitative analysis, including vascular volume, mean vascular diameter, and cut section area, supported these differences between DC and UC. CONCLUSIONS: The results suggest that vascular structures of gastric carcinomas are characteristic with regard to their histologic subtypes; DC is normovascular or hypervascular, whereas UC is hypovascular. PMID- 8508427 TI - Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. AB - BACKGROUND: In an attempt to decrease the toxic effects of fluorouracil, doxorubicin, and methotrexate (FAMTX) by reducing the dose of methotrexate from 1500 mg/m2, according to the original regimen, to 1000 mg/m2, the authors designed the modified FAMTX treatment that was evaluated in a prospective Phase II-III randomized trial. METHODS: Patients with advanced gastric cancer were randomized to receive modified FAMTX treatment or supportive measures only (control group). In the middle of the study, the randomization was interrupted because of strong evidence of benefit in terms of tumor reduction and projected survival in the treatment arm receiving chemotherapy. By the end of the study, 30 assessable patients had received chemotherapy and 10 had received supportive treatment. RESULTS: The overall response rate was 50% (15 patients); 12 patients (40%) had partial responses and 3 (10%) had complete responses (CR). One patient with extensive peritoneal carcinomatosis attained a CR pathologically documented by laparoscopic examination and peritoneal biopsy. The median overall survival time of the treated group was 9 months, whereas that of the control group was only 3 months (P = 0.001). The median overall survival time of the responders was 16 months, and their median remission duration was 8 months. The regimen was well tolerated, with a very acceptable toxicity profile. There was one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue. CONCLUSIONS: This regimen appears to prolong survival in patients with advanced gastric cancer, and the reduction of the methotrexate dose does not seem to compromise its efficacy. PMID- 8508428 TI - Tumor aneuploidy in young patients with colorectal cancer. AB - BACKGROUND: Colorectal cancer in young patients (40 years of age or younger) often is considered to have a worse prognosis than in older patients. The authors studied tumor DNA status and stage of disease to determine whether tumors in younger patients behaved differently from tumors in older patients. METHODS: This retrospective study identified 33 young patients with colorectal cancer treated surgically between 1979 and 1989. The DNA content of the tumors was analyzed by DNA flow cytometry. Results were compared with 75 cases of colon cancer in patients older than 40 years of age. RESULTS: Six of the 33 young patients had inadequate tissue for study. Four patients with ulcerative colitis were excluded. Tumor aneuploidy was present in 14 of 23 young patients (61%; mean age, 35 years) and 46 of 75 older patients (61%; mean age, 71 years). When Dukes staging was performed for the young patients, one had Stage A (4%), nine had Stage B (39%), eight had Stage C (35%), and five had Stage D (22%) disease. The control group had similar staging. The distribution of aneuploid tumors within each Dukes stage was also similar. Twenty-one young patients were available for follow-up. Four (31%) of 13 patients with aneuploid tumors died, whereas none of 8 patients with diploid tumors died. This trend was not statistically significant (P < 0.10). CONCLUSIONS: The frequency of tumor aneuploidy, stage of disease at presentation, and distribution of tumor aneuploidy within each stage was similar when young and old patients with colorectal cancer were compared. There is a trend toward tumor aneuploidy being associated with a poorer prognosis in young patients. PMID- 8508429 TI - Trends in subsite distribution of colorectal cancers and polyps from the Vaud Cancer Registry. AB - BACKGROUND: Changes in the subsite distribution of malignant and benign colorectal tumors over the last few years have been reported in several series. They may be related to changes in diagnostic accuracy or to real changes in incidence. METHODS: Trends in incidence and subsite distribution of colorectal cancers and polyps between 1978 and 1988 have been analyzed using data from the Cancer Registry of the Canton Vaud, Switzerland (530,000 inhabitants in 1981), which has adopted standardized methods for identification and registration not only of malignant, but also of benign colorectal lesions. RESULTS: Age standardized incidence rates for malignant tumors of the ascending colon in men increased from 4.6/100,000 in 1978-80 to 6.4/100,000 in 1987-88, and in women from 4.9 to 6.5. Incidence was approximately stable for transverse, descending, and sigmoid colon, whereas a decline was observed for "other and unspecified" colon cancers. Rates for rectal cancer declined by over 10% in both sexes, although the trends were not linear across calendar periods in each sex. Overall colorectal cancer incidence was relatively stable in both sexes in the Vaud population. In terms of proportional distribution, the percentage of cases in the ascending colon increased from 27% in 1978-83 to 33% 1984-88 (P < 0.05). Reliable incidence data for polyps were available for 1979 and from 1982 to 1988. Rates for ascending colon polyps increased from 1.0/100,000 in 1979-83 to 5.0/100,000 in 1987-88 in men, and from 0.4 to 2.7 in women. Incidence rates were higher, although to a lesser extent, for transverse colon and for descending colon polyps in men only. As in the case of malignant tumors, incidence rates declined between the early and the late 1980s for rectal polyps as well as for "other and unspecified" colon polyps. Overall, colorectal polyp incidence was stable around 45/100,000 for men but increased from 19 to 27/100,000 for women. With reference to proportional distributions, significant increases were observed for ascending (from 8.4% to 16.8%) and, to a lower degree, transverse colon (from 8.4% to 11.0%). No appreciable change was observed for any other subsite, except a decline for "other and unspecified" colonic polyps. CONCLUSIONS: The observation of similar changes in distribution for benign and malignant tumors may suggest the importance of improved diagnostic accuracy (particularly total colonoscopy) for lesions arising in the proximal colon. PMID- 8508430 TI - Prognostic factors in telecobalt therapy for early supraglottic carcinoma. AB - BACKGROUND: The local control rates of T1 and T2 supraglottic carcinoma treated with radiation alone were reported as 71% to 92% and 59% to 83%, respectively. The factors that affect the local control rate for early supraglottic carcinoma were investigated. METHODS: From 1967 through 1985, 100 cases with early supraglottic carcinoma (T1N0, 51; T2N0, 49) were treated with telecobalt therapy at the Department of Radiology, Osaka University Hospital. RESULTS: The 5-year actuarial survival rates of cases with T1 and T2 were 69% and 74%, respectively. The 5-year local control rates of cases with T1 and T2 were 77% and 62%, respectively. The local control rate for the epilarynx (94%) was significantly better than that for the lower supraglottis (66%; P < 0.05). For the lower supraglottis, the local control rates of 24 tumors that disappeared at 40 Gy and 58 tumors that persisted at 40 Gy were 88% and 55%, respectively (P < 0.05). CONCLUSIONS: The tumor site was an important prognostic factor in radiation therapy for the supraglottis, as was the tumor response at 40 Gy for the lower supraglottis. PMID- 8508431 TI - Primary chondrosarcoma of the lung. A clinicopathologic study. AB - BACKGROUND: Primary pulmonary chondrosarcoma is a rare neoplasm. A 73-year-old Japanese man had chondrosarcoma in the right lung. The tumor was considered to be of pulmonary origin because of the absence of extrapulmonary primary lesions for 2 years after lung resection. METHODS: The histologic sections were stained with hematoxylin and eosin, conventional special staining, and immunohistochemical staining. The authors discussed the differential diagnosis and growth pattern, in addition to the histopathologic findings in the tumor cells. In a review of the literature, the authors compared the characteristics between the major bronchus (MB) and lung types. RESULTS: Histopathologically, the tumor cells showed atypical cartilaginous differentiation without osteoid formation, benign or malignant-appearing epithelium, or sarcomatous components other than chondrosarcoma. The tumor showed expansive proliferation, invasion through the alveolar spaces, massive proliferation along the bronchial lumen, significant invasion into small vessels, and extrathoracic metastases. The review of the literature showed that the clinical period ending with surgical treatment was longer in the lung tumors than in the MB tumors. CONCLUSIONS: Although MB tumors were reported to be discovered early, the invasion to major arteries or trachea often led to inoperability; however, lung tumors were considered to be resectable until they grew very large, even though the clinical period from onset to surgical treatment was longer in this type. Recent advancements in diagnostic and surgical techniques are expected to promote early discovery and improve prognosis whether the tumor occurs in the MB or lung. PMID- 8508432 TI - Correlation of expression of ABH blood group carbohydrate antigens with metastatic potential in human lung carcinomas. AB - METHODS. The expression of ABH blood group carbohydrate antigens was examined histochemically in tumors and adjacent nontumorous tissues of 89 cases of human lung carcinoma in which nontumorous tissues expressed blood group carbohydrate antigens compatible with the erythrocyte blood group types. RESULTS AND CONCLUSIONS. Loss of ABH blood group antigens in lung carcinomas correlated with their metastatic potential, especially with the recurrence of hematogenous metastasis. Consequently, patients with tumors that retained compatible ABH blood group antigens showed a better prognosis than patients with tumors of altered antigenic profiles. The loss of blood group B antigen more significantly affected both the hematogenous metastasis and prognosis than that of A and H antigens. PMID- 8508433 TI - Prophylactic treatment of skeletal metastases, tumor-induced osteolysis, and hypercalcemia in rats with the bisphosphonate Cl2MBP. AB - BACKGROUND: The purpose of this study was to investigate the influence of a prophylactic bone protective treatment with the bisphosphonate dichloromethane/diphosphonic acid (Cl2MBP) in an experimental model of osteolysis with intraosseous implantation of the Walker carcinosarcoma 256 B. METHODS: The biphosphonate was given as a high-dose, short-term treatment (30 mg/5 days sc) followed by a treatment-free interval (1-7 weeks) or as a low-dose, long-term prophylactic treatment (2.5 or 5.0 mg/day/3 weeks sc). Osteolysis was measured with a radiographic and histologic grading system. RESULTS: The high-dose short term prophylactic treatment was shown clearly to inhibit tumor osteolysis. The osteoprotective effect decreases with increasing length of the treatment-free interval. A similar positive result could be achieved following the low-dose long term prophylactic treatment. Dosage could not be shown to influence the inhibition of tumor osteolysis in the long-term bone protective treatment. A possible direct influence of the treatment on tumor growth could be ruled out. The prophylactic treatment does not inhibit body weight increase. Animals treated prophylactically showed less weight loss than the controls after tumor implantation. CONCLUSIONS: These results show that a prophylactic treatment with Cl2MBPs protects the skeleton effectively against tumor osteolysis. PMID- 8508434 TI - Kangaroo care. AB - Kangaroo care is the practice of holding a small, premature infant, naked except for a diaper and hat, against a parent's chest. This skin-to-skin contact resembles how marsupials such as kangaroos and koalas care for their young. Initially established in overcrowded nurseries in developing countries as a substitute for incubators and monitors, kangaroo care is now practised in the neonatal intensive care units of developed countries. PMID- 8508435 TI - Terminal illness. AB - Computers proliferate in almost every workplace of today. Unfortunately, society seems to have been more interested in mass-producing computer systems than in the health and comfort of the humans who interact with them. The unhappy consequence has been a growing rate of computer-related injuries. Nursing worksites are far from immune to this "terminal" illness; the health hazards associated with radiation, stress and workplace design have brought ill health to nurses and to other workers. But like other health problems, computer-related illness can be avoided through preventive care. PMID- 8508436 TI - Sexual assault: coping with crisis. AB - An unexpected long-distance phone call after midnight started the day. Susan, the daughter of an old friend, had been sexually assaulted. Mother and daughter had just returned from the emergency department, where Susan had been examined and treated. Now, they felt abandoned and hopeless. "Susan feels as if she was raped again by physicians, police and you nurses," shouted her mother. "I thought professionals were helpers!" PMID- 8508437 TI - Saying no--completely. AB - Has the health care system over-guarded the social rights of alcohol? Listening to the testimonies of several parents with fetal alcohol syndrome (FAS) and fetal alcohol effect (FAE) children led Jill Courtemanche, nurse and unit administrator at the Children's Hospital of Eastern Ontario, to believe so. PMID- 8508438 TI - A dangerous lack of understanding. AB - In the past, inadequate information on the effects of maternal alcohol consumption on the fetus meant that not enough emphasis was placed on this topic in prenatal and preconceptual teaching. Today, fetal alcohol syndrome is a widely accepted diagnosis in the medical community. Health professionals now stress the importance of abstinence from alcohol during pregnancy, especially during the first trimester. Unfortunately, a surprising number of adults have but a meagre knowledge of the risks. This dangerous lack of understanding represents a failure in health promotion. PMID- 8508439 TI - Rehab and self determination. AB - Recent knowledge that personal well-being is related to lifestyle has brought health promotion and disease prevention strategies to the fore. Tremendous responsibility is placed on health care workers as they influence the process of human well-being and aid in altering health-damaging behaviors. Under the Hippocratic ethic that dominates health care, the potential for abuse of this influence is tremendous. This paternalistic ethic "leaves no room for the principle of self-determination--a principle at the core of liberal Western thought." When a patient's views about his or her best interest conflict with the views of the professional, the Hippocratic ethic would urge the dominance of the professional's viewpoint. PMID- 8508440 TI - Working can be harmful to your health. AB - Today, most public and private organizations are aware of statistics showing that hard-earned profits are being wasted to absenteeism; work accidents and illnesses; poor product quality; decreased production; labor conflicts; increased turnover of staff, and errors of commission or omission. What may be less clear are the causes of these problems. An examination of the psychosocial environment of the workplace sheds light on the subject. PMID- 8508441 TI - [Is the health care plan pertinent?]. AB - The author presents them as one of a number communication tools available to nurses. For many nurses, care plans pose a problem--for various reasons. While the majority of Quebec short term care hospitals are receiving recommendations to improve part or all of their nursing care plans, the American Commission is revising standards identifying care plans as optional. Should they be mandatory? The author maintains that the debate surrounding their use be refocussed so that they don't become more important than the function for which they were initially intended. Given that they were developed to achieve specific goals, their importance is secondary to nursing unit goals. This point is illustrated through the use of a table showing the relative importance of nursing care plans within a unit. The author describes nursing care plans as part of the overall nursing process, as well as a single element within an information system. He maintains that the entire nursing information system, not just nursing care plan, needs to be reviewed. He concludes that nursing care plans are appropriate as long as they correspond to a real need and are perceived as necessary. If the opposite is true, then their use should be reconsidered. PMID- 8508444 TI - Miraculous healing. PMID- 8508443 TI - [Feminist strategies 2]. AB - This article is the second in a two-part series promoting the use of feminist strategies in nursing. Part one--in last month's issue--identified some of the myths in nursing. It focused mainly on the traditional scientific research methods upon which nursing research is based. In part two, the author defines the feminist approach and attempts to demonstrate the way nurses can use this approach to focus nursing care on women's specific needs. This approach consists of recognizing the components of patriarchal ideology, its myths and the reality of women and men. Feminism has restored the credibility of intuition, good listening skills, compassion, commitment and tolerance. They were long believed to be "feminine" and passive. These qualities do not discredit the women who possess them--many of whom are nurses, rather, they add to their competence. How can feminist nursing knowledge shed light on the different factors specific to a woman's life? Menopause, nutrition and domestic violence are examples presented by the author to address this question. Once nurses increase their knowledge of these factors--that up until now were not identified as women's needs--they will be able to rely upon their own capabilities to develop new methods of data collection, communication skills and promotion of their own professionalism. Through these conclusions, the author praises the feminist movement. PMID- 8508442 TI - [The frequent screams]. AB - Functional analysis is a research process that links problem behavior, its surrounding elements and the resulting consequences. The goal of this study was to decrease repetitive shouting of an elderly patient diagnosed with Alzheimer like dementia. The analysis provided the following data: BEHAVIORS: Repetitive shouting by the patient lasting 80-115 seconds per 30 minutes during specific times of the day--accompanied by licking of the lips to moisten them. Environmental factors: Constant loud noise in the patient's room; the use of loud voices by staff and visitors; familiar objects out of the patient's reach. Individual factors: Diagnosis of the patient's blindness and auditory hypersensitivity; side-effects of psychotropic medications; a lack of social activities; inactivity because of the patient being bedridden 22 hours per day and the use of restraints when positioned in a chair. SURROUNDING ELEMENTS: The patients was isolated in a private room; psychotropic medication was increased; staff and other patients were less disrupted and the number of visitors to the patient was decreased. CONSEQUENCES: The above data enabled the formulation of four hypotheses (with specific interventions for each) that assisted staff in planning the patient's care for a 10-day period; a reduction of anxiety; a reduction in discomfort; sensory hypostimulation; verbal hypostimulation. Following the application of these interventions for a 10-day period, a second set of data was gathered and the results showed a decrease in shouting by 40 per cent in the morning and 51 per cent in the afternoon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508445 TI - Health, illness and Christian faith. PMID- 8508446 TI - Healing & forgiveness. PMID- 8508447 TI - Exercise testing. Procedures and implementation. AB - Although important strides have been made in related procedures, exercise ECG remains an invaluable tool in the initial assessment of coronary disease and yields a great deal of prognostic information. Access to limited health care resources often hinges on its outcome. Proper methodology is critical to patient safety and to obtain accurate results. The importance of patient education, physician interaction with the patient, skin preparation, and criteria for exclusion and termination cannot be overemphasized. A brief physical examination and 12-lead ECG in both the supine and standing positions should precede exercise testing. Few studies have correctly evaluated the relative yield or sensitivity and specificity of different electrode placements for exercise-induced shifts in the ST segment. The use of other leads in addition to V5 increases test sensitivity, but the specificity may be reduced. ST-segment changes isolated to the inferior leads are frequently false-positive responses. Vectorcardiographic and body surface mapping lead systems do not appear to offer any advantage over simpler approaches for clinical purposes. Changes caused by exercise electrode placement can be kept to a minimum by placing arm electrodes on the shoulders, off of the chest. The exercise protocol should be progressive, with even increments in speed and grade whenever possible. Smaller, even, and more frequent work increments are preferable to larger, uneven, and less frequent increases, because the former yield a more accurate estimation of exercise capacity. The value of individualizing the exercise protocol rather than using the same protocol for every patient has recently been emphasized by many investigators. The optimal test duration is from 8 to 12 minutes, and the protocol workloads should be adjusted to permit this duration. Because ramp testing uses small increments, it permits a more accurate estimation of exercise capacity and can be individualized for every patient to yield a targeted test duration. Target heart rates based on age should not be used because the relationship between maximal heart rate and age is poor and varies greatly. The Borg scale is a useful means of quantifying an individual's effort. Exercise capacity should not be reported in total time but rather as the VO2 or MET equivalent of the workload achieved. This permits comparison of the results between many different exercise testing protocols. Gas-exchange techniques can greatly supplement exercise testing by adding precision and reproducibility and increase the yield of information concerning cardiopulmonary function. Estimating work from treadmill or cycle ergometer workload introduces a great deal of error and variability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8508448 TI - Exercise test interpretation. AB - The interpretation of an exercise test should encompass both subjective and objective aspects derived from testing. The patient's appearance, symptoms, and physical examination form an important part of the exercise test as do the hemodynamic responses of blood pressure and heart rate. In addition, the assessment of exercise capacity has been correlated to diagnosis and prognosis of patients with heart disease. Moreover, exercise-induced electrocardiographic changes provide the clinician with markers of cardiac pathology, which together with hemodynamic and clinical responses complete the exercise interpretation. PMID- 8508449 TI - The prognostic value of exercise testing. AB - This article discusses the prognostic value contained in exercise testing in patients with cardiac diseases. Exercise testing is a valuable mean of risk stratification and assessment of therapeutic intervention of cardiac patients that complements history and physical examination in the management of these patients. PMID- 8508450 TI - Exercise testing in special situations. AB - This article discusses exercise testing in valvular heart disease, hypertension, and the evaluation of patients for surgery. It also provides information on the effects of drugs on the exercise test and the clinical significance of block patterns and arrhythmias encountered during exercise. PMID- 8508451 TI - Exercise testing in cardiac rehabilitation. Role in prescribing exercise. AB - Graded exercise tests provide useful information for the prescription of exercise for cardiac patients. The responses to graded exercise depend on the mode of testing. The observed heart rate and electrocardiographic responses during graded exercise are used to establish an appropriate level or intensity of exercise at which the patient may participate safely. This article specifically addresses the role of exercise testing for the prescription of exercise in cardiac rehabilitation. PMID- 8508452 TI - Rehabilitative exercise for the cardiac patient. Early phase. AB - The early phase of cardiac rehabilitation provides an opportunity for patient education and coronary risk factor modification with exercise training. In addition, a diagnostic evaluation can be performed from the vantage of detecting changes in myocardial ischemia, heart rate, and rhythm, particularly in the monitored phase. During this early phase of cardiac rehabilitation, an extension of the evaluation of each patient can be performed before he or she begins more independent types of cardiac rehabilitation with less professional supervision. When these early phases of rehabilitation are properly carried out, the education and diagnostic components can be maximized for the patient and, thus, aid in stabilizing therapy before the patient is allowed freedom in the rehabilitative process or the opportunity of individually performing in a self-monitored program. PMID- 8508453 TI - Exercise for the cardiac patient. Long-term maintenance phase. AB - Exercise is an important part of the long-term management of patients with heart disease. Patients should be screened carefully and receive an exercise prescription that is safe and effective based on their exercise test results. For the safest programs, individuals should either restrict their activity to moderate intensities or exercise in the presence of medical supervision. The results of such programs have been shown to improve both the quality and quantity of life. PMID- 8508454 TI - Home-based and worksite-based exercise training for patients with coronary artery disease. AB - In the era of thrombolysis, exercise training for patients with ischemic heart disease should be reserved for enhancement of functional capacity and psychological well-being rather than improvement of prognosis. Low to moderate intensity exercise training enhances functional capacity to the same extent that group-based exercise training does and can be performed safely at home. The physical demands of occupational work have decreased to the point where patients with ischemic heart disease who manifest neither treadmill-induced myocardial ischemia nor left ventricular dysfunction can perform virtually any occupational task. PMID- 8508455 TI - Types of exercise. Arm-leg and static-dynamic. AB - Exercise training for patients with heart disease is no longer limited to a monotonous single-activity routine. Training regimens can and should employ a wide variety of activities that involve the arms and legs and both dynamic and static effort (Table 3). Because the physiologic and, hence, ischemic responses to each type of exercise are different, the unique properties of the varying forms of exercise must be well understood. Significant cardiovascular benefit can be derived from a training program that employs a diversity of activities in a safe and effective manner. Improvements in muscular endurance and strength, with reductions in ischemia, can translate to a more satisfying and productive life for the patient with heart disease. PMID- 8508456 TI - Special populations in cardiovascular rehabilitation. Peripheral arterial disease, non-insulin-dependent diabetes mellitus, and heart failure. AB - Exercise rehabilitation has traditionally been part of the management of patients with coronary artery disease, particularly in the recovery period from a myocardial infarction or after coronary artery bypass surgery. The benefits of exercise training and formal rehabilitation programs are not limited to patients with coronary artery disease, and special populations described in this article should be considered for rehabilitation services. Patients with PAD are frequently severely limited by claudication pain. Exercise rehabilitation is an effective means to improve exercise performance without the use of drugs or operation. In patients with NIDDM, an exercise program not only improves exercise performance (which is impaired as compared with age-matched controls) but also improves glucose metabolism and insulin sensitivity. Patients with left ventricular dysfunction have a severely limited peak exercise performance. In these patients, an exercise program can be conducted safely in a supervised setting and will result in a significant improvement in peak oxygen consumption. PMID- 8508457 TI - Psychobehavioral treatment in cardiac rehabilitation. AB - This article reviews the empirical evidence for the use of behavioral and psychological therapies in the rehabilitation of patients with coronary disease. Exercise training, Type A modification, psychological counseling, smoking cessation, and dietary modification are considered. It is concluded that psychobehavioral therapies offer considerable promise to coronary patients in improving quality and quantity of life. PMID- 8508459 TI - CIRSE '93. Annual meeting and postgraduate course of the Cardiovascular and Interventional Radiological Society of Europe Budapest, June 20-24, 1993. Abstracts. PMID- 8508458 TI - Efficacy studies in coronary rehabilitation. AB - Demand for cardiac rehabilitation services is likely to increase as the prevalence of coronary heart disease increases due to aging of the population and as interventions such as thrombolysis, revascularization, and cardiac transplantation allow more patients to participate in structured exercise programs. In this era of cost containment, advocates of the rehabilitation process must demonstrate which rehabilitation services are efficacious. Optimal training intensities and frequencies in different patient groups must be defined, innovative approaches to improve long-term adherence to the prescribed exercise regimen have to be developed, and interactions between exercise training and other interventions such as diet, weight loss, and pharmacologic therapy must be explored in detail to provide the most desirable long-term outcomes. PMID- 8508460 TI - Stressors and perceived stress in older women with heart disease. PMID- 8508461 TI - [Pimozide in the treatment of psychogenic eating disorders]. AB - PIMOZIDE was given to 14 pat. with anorexia nervosa and 21 pat. with bulimia nervosa The drug evaluated positively some symptoms of eating disorders. Most significantly it improved the bulimic episodes and purging. The accompanying psychiatric symptomatology (depression and anxiety) was mostly not improved. We conclude that Pimozide may be a useful medication in the therapy of basic symptoms (bulimia, purging) in bulimic forms of eating disorders. PMID- 8508462 TI - [Treatment of polyneuropathy using sabeluzole]. AB - Two groups of patients suffering from polyneuropathy were treated by sabeluzol. The first group--a double blind placebo controlled study consisting of 30 diabetics of type II did not prove either significant differences of their subjective complaints or changes of their objective findings (the dose of sabeluzole being 2 x 10 mg/d). The second group--open study--consisting of 26 patients suffering from polyneuropathy of various origin, treated by sabeluzole 3 x 10 mg/d. The therapeutic effect was significantly higher in comparison to the above mentioned lower doses of the medicament (manifesting statistical significance of 5 and 10%); the authors make a point of sabeluzol's therapeutic efficacy, especially in cases with acute polyneuropathy onset and point out the necessity of several months lasting treatment. Positive effect upon the pseudoneurasthenic syndrome in many patients indicates its usefulness also in other disorders than are these of polyneuropathy. PMID- 8508463 TI - [Flunarizine and sabeluzole improves behavior disorders caused by cold-induced cortical lesions in mice]. AB - The present paper reports two experiments is which an effect of sabeluzole and flunarizine upon behavioural consequences reflecting ischemic damage following cortical freezing lesions was evaluated in NMRI female mice. The parietal lesion was performed by applying a flat (2 mm in diameter) of a metal probe cooled to 75 degrees C on the exposed skull for 5 s. Flunarizine (15 mg/kg) was administered sc 1 hr before and 4 hr after performing the lesion and then, 1 mg/kg p.o. once daily for 14 days. Sabeluzole (5 mg/kg) was administered p.o. 1 hr before and 5 hr after performing the lesion and then, 5 mg/kg p.o. once daily for 14 days. Hole--board method was used to evaluate the exploratory head-dips activity of an animal in 5 sessions separated by 24 hr intervals during the postlesion testing from the 20th to the 24th day, i.e. from day 6 to 10 after finishing the treatment. The session lasted 5 min. In both experiments, the mean number of exploratory hole visits in lesioned female mice was significantly increased. Both flunarizine and sabeluzole reduced high hole exploration of lesioned mice to levels corresponding to those of the controls. Neither flunarizine nor sabeluzole affected significantly exploratory hole visit of control animals. Results showed that flunarizine as well as sabeluzole ameliorated behavioural disturbances reflecting the brain impairment induced through cortical freezing lesion. This effect is most probably related to the protective effect of both drugs against hypoxia induced in laboratory animals by several experimental procedures. The hole--board method seems to be suitable for the screening of compounds considered as cerebroprotective drugs. PMID- 8508464 TI - [The consultant ("liaison") psychiatrist and psychologist: his position and tasks in non-psychiatric health care facilities]. AB - The author summarizes findings assembled during his 25 years of experience as a consulting psychiatrist in medical and surgical departments. He defines the basic groups of actual problems the solution of which is most frequently needed: states of confusion, depression, crises, psychosomatic problems in the narrower sense of the word, conflicts between patients and staff, psychoprophylactic work and research. He emphasizes the demand of an integrated biopsychosocial approach. PMID- 8508465 TI - [Parental divorce and sexual development in girls]. AB - Using interviews, the authors examined the course of sexual development during puberty in 614 girls aged 16-18 years. The group was divided into two sub-groups. The first was formed by 426 girls (69.4%) brought up in a complete and balanced family. The other sub-group was formed by 140 girls (22.8%) of divorced parents with the loss of the father or mother. Statistical evaluation of data did not reveal significant differences in the sub-groups as regards their sexual pubertal development. PMID- 8508466 TI - [Psychiatric disorders in the Vietnamese]. AB - In a review of psychiatric problems of the Vietnamese population in particular experiences with refugees to the USA are mentioned where with regard to the great influx it was necessary to resolve rapidly in particular problems of the mental health. The group is formed by 20 Vietnamese subjects (11 men and 9 women) who were hospitalized in 1979-1988 at the Prague Psychiatric Clinic, Charles University and who had various jobs in Prague. In six men psychosis was diagnosed (3x schizophrenia or schizoaffective psychosis, 2x depressive phase and 1x manic phase of manic depressive psychosis). In women the psychopathological symptoms were evaluated as neurotic, in 6 of them there were attempts of suicide, while in men suicidal behaviour was recorded only once. Regardless of sex, the suicidal attempts were made with great determination. Aggressive behaviour focused on the environment was found in three men. The authors describe cases of somatizing depression and hysterical manifestations. In the development of symptoms participated psychogenic factors such as separation from the home country, partnership conflicts, incl. unwanted pregnancy and unsatisfactory work. Some psychopathological symptoms reminded of experience with the so-called Gastarbeitersyndrom. PMID- 8508467 TI - Modification of the amino group of guanosine by methylglyoxal and other alpha ketoaldehydes in the presence of hydrogen peroxide. AB - Methylglyoxal is directly mutagenic to Salmonella typhimurium TA100 and its mutagenicity is markedly enhanced in the presence of hydrogen peroxide. We found that methylglyoxal in phosphate buffer was decomposed easily by hydrogen peroxide at room temperature to yield acetic acid and formic acid as major products and diacetyl as a minor product; acetyl radical was detected in the solution by ESR spectroscopy by the use of a spin-trapping reagent, 5,5-dimethyl-1-pyrroline N oxide. Furthermore, guanosine was converted into N2-acetylguanosine by a combination of methylglyoxal and hydrogen peroxide in 0.1 M phosphate buffers (pH 6.1 to 7.4). This acetylation may be related to the enhancement of methylglyoxal mutagenicity by hydrogen peroxide. Other alpha-ketoaldehydes such as glyoxal and phenylglyoxal also yielded the corresponding acids and alpha-dicarbonyls upon reaction with hydrogen peroxide under the same conditions as above. These acids would have been produced through Baeyer-Villiger reaction or coupling of acyl radical with hydroxy radical, and dicarbonyls by dimerization of acyl radicals. In addition, when phenylglyoxal was used, the generation of benzoyl radical and the conversion of guanosine to N2-benzoylguanosine were observed. However, it remains to be established whether the generation of acyl radicals is directly involved in the N-2 acylation of guanosine. PMID- 8508468 TI - Identification of immunosuppressive components of a mushroom, Lactarius flavidulus. AB - Three metabolites having a suppressive effect on proliferation of mouse lymphocytes stimulated with mitogens such as concanavalin A (Con A) and lipopolysaccharide (LPS) were isolated from a mushroom, Lactarius flavidulus, and identified as geranylphenols, flavidulols A, B and C, respectively, which had previously been isolated from the same mushroom. The IC50 values of flavidulols A, B and C were found to be 8.9, 4.9 and 36.3 micrograms/ml against Con A-induced proliferation of mouse lymphocytes, and 6.7, 3.9 and 28.3 micrograms/ml against LPS-induced proliferation, respectively. PMID- 8508469 TI - Studies on the constituents of Aster scaber Thunb. IV. Structures of four new echinocystic acid glycosides isolated from the herb. AB - Four new echinocystic acid 3,28-O-bisdesmosides, scaberosides Ha, Hb1, Hb2 and Hc1, were isolated as their methyl esters from the ground part of Aster scaber THUNB. (Compositae) along with foetidissimoside A and scaberoside A2, and their structures were determined based on spectral and chemical evidence. These glycosides have a common prosapogenin structure, echinocystic acid 3-O glucopyranosiduronic acid, and differ in the structures of the 28-O-linked sugar moieties. Scaberoside Ha1 is a 28-[O-alpha-L-rhamnopyranosyl-(1-->2)-[O-alpha-L rhamnopyranosyl-(1-->3) ] - beta-D-xylopyranosyl] ester, Hb1, a 28-[O-beta-D xylopyranosyl-(1-->4)-O-alpha-L-rhamnopyranosyl-(1-->2)- [O-alpha-L rhamnopyranosyl-(1-->3)]-beta-D-xylopyranosyl] ester, Hb2, a 28-[O-beta-D xylopyranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1-->4)-O-alph a-L- rhamnopyranosyl (1-->2)-[O-alpha-L-rhamnopyranosyl-(1-->3)]-beta-D- xylopyranosyl] ester, and Hc1, a 28-[O-beta-D-xylopyranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1-->3)-[O-bet a D-xylopyranosyl-(1-->4)]-O-alpha-L-rhamnopyranosyl-(1-->2)-[O-alpha-L- rhamnopyranosyl-(1-->3)]-beta-D-xylopyranosyl] ester of the prosapogenin. PMID- 8508471 TI - Rapid determination of a new angiotensin-converting enzyme inhibitor, imidapril, and its active metabolite in human plasma by negative-ion desorption chemical ionization-tandem mass spectrometry (MS/MS). AB - A very rapid and highly sensitive method using desorption chemical ionization (DCI)-tandem mass spectrometry (MS/MS) with selected reaction monitoring is reported for the simultaneous determination of imidapril and its active metabolite (M1) in human plasma. Imidapril and M1 in plasma were extracted by a C18 solid phase extraction cartridge after deproteinization, and derivatized with pentafluorobenzyl bromide. One microliter of prepared sample was applied to the DCI filament and analyzed by DCI/MS/MS within a few minutes. The limits of determination of imidapril and M1 were 0.2 and 0.5 ng/ml in human plasma, respectively. The features of this method make it appropriate for use in pharmacokinetic studies with human plasma after oral administration of imidapril. PMID- 8508470 TI - Studies on novel bone resorption inhibitors. I. Synthesis and pharmacological activities of aminomethylenebisphosphonate derivatives. AB - A series of aminomethylenebisphosphonate derivatives was synthesized and evaluated for their antiresorptive activities using a parathyroid hormone (PTH) induced hypercalcemia model in rats (PIH model). Among these compounds, (cycloheptylamino)methylenebis(phosphonic acid) (3j) was finally selected for further investigation, proving 10-fold as potent as pamidronate in the PIH model and an immobilization bone atrophy model in rats (DA model). The structure activity relationships of this series of bisphosphonates are discussed. PMID- 8508472 TI - Cyclic peptides, acyclic diterpene glycosides and other compounds from Lycium chinense Mill. AB - The chemical structures of four cyclic peptides, lyciumins A-D (1-4), three acyclic diterpene glycosides, lyciumosides I-III (5-7) and other three compounds, a tryptophan derivative glycoside (8), a monoterpene glycoside (9) and a steroidal glycoside (10) isolated from Lycium chinense, have been elucidated by a combination of chemical, 1H- and 13C-NMR, and mass spectrometric studies. Lyciumins are interesting because of their monocyclic octapeptides containing a novel C-N linkage between tryprophan N1 and glycine C alpha. PMID- 8508473 TI - Cholesterol biosynthesis inhibitory component from Zingiber officinale Roscoe. AB - We previously reported on the isolation and identification of (E)-8 beta,17 epoxylabd-12-ene-15,16-dial (ZT) from ginger (rhizome of Zingiber officinale Roscoe, Zingiberaceae). In this paper, the pharmacological effects of ZT are reported. The experimental mouse hypercholesterolemia induced by Triton WR-1339 was treated after oral administration of ZT. In homogenated rat liver with ZT, cholesterol biosynthesis was decreased. In addition, the same activity was observed in the homogenated rat liver which was resected after the oral administration of ZT. According to the results of general pharmacological screening, no remarkable activity of ZT was observed except for an inhibitory effect on the cholesterol biosynthesis. PMID- 8508474 TI - Studies on the differentiation inducers of myeloid leukemic cells from Citrus species. AB - An attempt was made to isolate differentiation inducers from Aurantii Nobilis Pericarpium and the fruit peel of Citrus reticulata Blanco (Rutaceae). Twenty seven kinds of flavones, including five new flavones, were isolated after repeated chromatography from methanol extracts of these plants and their structures were established, from their physicochemical data, to be highly methoxylated flavones. Each compound, except for two flavone glucosides, showed the differentiation inducing activity toward mouse myeloid leukemia cells (M1), and the cells came to have phagocytic activity. Furthermore, differentiation inducing activity was tested using human acute promyelocytic leukemia cell line (HL-60). PMID- 8508475 TI - Effects of water content on physical and chemical stability of tablets containing an anticancer drug TAT-59. AB - (E)-4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1 butenyl]phenyl monophosphate (TAT-59) is a new drug for the treatment of breast cancer. Physical and chemical stability of a tablet consisting of TAT-59 powder and a few excipients (Formulated tablet), a tablet consisting of only TAT-59 powder (TAT-59 tablet) and TAT-59 powder itself was evaluated based on water content, tensile strength, porosity, the amount of TAT-59 and its hydrolysis product, DP-TAT-59. The water content of Formulated tablet increased with relative humidity (RH), whereas that of TAT-59 tablet and TAT-59 powder scarcely changed. The equilibrium water content of Formulated tablet was much greater than that of the TAT-59 tablet or TAT-59 powder due to adsorbed moisture by the excipients. The tensile strength and porosity of Formulated tablet decreased and increased linearly, respectively, with increasing water content. The degradation rate of TAT-59 decreased in the following order: Formulated tablet > TAT-59 tablet > TAT-59 powder. The relationship between equilibrium water content and degradation rate of the Formulated tablet was determined by the Carstensen equation, in which the interaction order between the drug and water content was 1.9, and the degradation of TAT-59 in Formulated tablet was related to water content. Thus, it was found that the degradation of TAT-59 was accelerated by compression and addition of excipients. PMID- 8508476 TI - Improved oral absorption of a poorly water-soluble drug, HO-221, by wet-bead milling producing particles in submicron region. AB - N-[[[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 nitrobenzamide (HO-221) is being developed as an anticancer agent with a novel mode of action. HO-221 shows poor oral absorption and is only slightly soluble in water (0.055 micrograms/ml at 37 degrees C). In this study, it was shown that the reduction in particle size of HO-221 to the submicron region (0.453 microm, mean by volume) could be achieved by a wet milling in a decaglycerin monolaurate aqueous solution with small glass beads. The wet milling suspension obtained showed improved dissolution rate and oral absorption in rats. A solid dosage form could also be made from that suspension with addition of sucrose palmitate which prevented aggregation caused by the hydrophobic interaction. The solid dosage form thus obtained showed twice as much oral absorption in dogs as the preparation made by dry milling. PMID- 8508477 TI - Orally active cephalosporins. IV. Synthesis, antibacterial activity and oral absorption of 3-(1H-1,2,3-triazol-4-yl)thiomethylthio-cephalosporins. AB - The synthesis, antibacterial activity and oral absorption of 3-(1H-1,2,3-triazol 4-yl)thiomethylthio-3-cephem-4-carboxyli c acids with various C-7 side chains (2) are described. The (1H-1,2,3-triazol-4-yl)thiomethylthio C-3 side chain was found to be an effective substituent for good oral absorption of cephalosporins with some C-7 side chains. PMID- 8508478 TI - Adsorption of mexiletine onto activated charcoal in macrogol-electrolyte solution. AB - Adsorption studies in vitro of mexiletine onto activated charcoal were performed in macrogol (polyethylene glycol)-electrolyte solution (PEG-ELS) and JP XII disintegration medium No. 2 (second medium). Mexiletine was adsorbed more extensively onto activated charcoal in PEG-ELS than that in JP XII second medium. The maximum adsorptive capacity of activated charcoal for the drug was 328 and 284 mg per gram of charcoal in PEG-ELS and JP XII second medium, respectively. In addition, the equilibrium constant of activated charcoal estimated according to the Langmuir equation was 0.079 and 0.034 l per gram of charcoal in PEG-ELS and JP XII second medium, respectively. Adsorption of mexiletine onto activated charcoal was decreased by omitting macrogol, sodium sulfate or sodium bicarbonate from a standard PEG-ELS formulation. Oral activated charcoal will be useful in combination with whole bowel irrigation with PEG-ELS in mexiletine overdose because of its excellent adsorbability in the solution. PMID- 8508479 TI - Alteration of hepatic DNA synthesis in rats treated with N-nitrosodimethylamine during early stages of copper deficiency. AB - The main aim of this research was to clarify that nutritional dietary copper may participate in the protective action against hepatocarcinogenesis in rats by N nitrosodimethylamine (NDMA). The copper concentrations in serum and liver from 2 to 8d after rats were first fed a copper deficient diet (copper, 0.6 ppm) decreased significantly compared to those of pair-fed rats (copper in a control diet, 7 ppm). The subcellular distribution of copper in the liver at 5d after feeding of a copper deficient diet began was measured and the copper concentrations in soluble and nuclear fractions decreased at a similar rate in copper deficient rats treated with or without NDMA, compared to those of pair-fed rats. The incorporation of [3H]thymidine into rat liver DNA at 48 h after treatment with NDMA markedly increased under the experimental conditions used. By giving rats a copper deficient diet for a few days the increased incorporation of [3H]thymidine into liver DNA of rats treated with NDMA was enhanced compared to that of pair-fed rats treated with NDMA. The activity of thymidine kinase in liver of copper deficient rats treated with NDMA was also found to increase significantly compared to that of pair-fed rats treated with NDMA. PMID- 8508480 TI - Redox potential of oligonucleotide linked to 5-deazaflavin coenzyme model. Detection of hybrid formation by cyclic voltammometry. PMID- 8508481 TI - Conformational recognition of RA-XII by 80S ribosomes: a differential line broadening study in 1H NMR spectroscopy. AB - 1H NMR spectroscopy has been used to demonstrate specific binding of rat 80S ribosomes to the major conformer of an antitumor bicyclic hexapeptidic glucoside, RA-XII, isolated from Rubia cordifolia, in a fast exchange process. PMID- 8508482 TI - [Nursing care of 168 cases of pig thyroid gland poisoning]. PMID- 8508483 TI - [Nursing care of abstinent patients with heroin addiction]. PMID- 8508484 TI - [Nursing care of inhalation injury of the respiratory tract in neonates]. PMID- 8508485 TI - [Nursing care of posterior cranial fossa hematoma in children]. PMID- 8508486 TI - [Response on cardiovascular effects of regional analgesia during internal ophthalmopathy surgery]. PMID- 8508487 TI - [Improving the teaching methods of nursing administration]. PMID- 8508488 TI - [A teaching technique for nursing students to learn drugs by singing songs with drug rhyames]. PMID- 8508489 TI - [Discussion on buildings and layouts in medical supply centre]. PMID- 8508490 TI - [Advances in nursing care of intra-abdominal infections in surgery]. PMID- 8508491 TI - [Dirigation after hip arthroplasty done by transplantation of island fascial flap with vascular pedicle]. PMID- 8508492 TI - [Complications of coronary angiography]. PMID- 8508493 TI - Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat. AB - Male F344 rats were treated with lead nitrate and changes in the expression and induction of P450IA subfamily enzymes and a placental form of glutathione-S transferase (GST-P) in the liver were assessed by means of a bacterial mutation test, immunoblotting with a monoclonal antibody reactive to P450IA1/IA2 and anti GST-P sera and Northern blotting with P450IA2 cDNA as a probe. Treatment of rats with lead nitrate (20, 50 or 100 mumol/kg body wt) decreased P450IA2 mRNA and protein in the liver in the dose-dependent fashion and also decreased the microsomal activity for P450IA2-dependent mutagenization of aromatic amines. Pretreatment of rats with lead nitrate suppressed the inductions of both P450IA2 mRNA and protein by an inducer of P450IA subfamily enzymes in the liver. In addition, amount of the induced P450IA2 was decreased along with increase in that of the induced GST-P. PMID- 8508494 TI - Effect of orotic acid on beta 1,4-galactosyltransferase during liver regeneration. AB - The study was designed to understand the effect of orotic acid (OA) on the expression of beta 1,4-galactosyltransferase (GalTase), an enzyme involved in the transfer of galactose from UDP-galactose to a non-reducing terminal N acetylglucosamine of a glycoprotein or glycolipid. Rats were fed a semisynthetic diet containing 1% OA for 2 weeks and the livers were stimulated to regenerate by two-thirds partial hepatectomy (PH). The level of activity of the enzyme and the steady-state level of hepatic mRNA transcripts of GalTase were determined prior to PH and at 12, 24, 48, 72 h and 10 days after the surgery. The data show that the hepatic activity of GalTase is unaltered in both the control and OA-fed groups until 12 h following surgery, but begins to increase after this time period. In the control group a progressive increase was seen throughout the experimental period following PH. On the other hand in the OA-fed group 24 h after PH the initial increase seen up to 24 h was arrested later on and the activity remained inhibited throughout the rest of the experimental period. The supplementation of 1% OA diet with 0.3% adenine, which is known to reverse the OA induced imbalance in the nucleotide pool sizes, relieved the inhibition of GalTase activity. The steady-state level of hepatic mRNA paralleled the activity of GalTase at all the time points studied during liver regeneration. The reduction in the level of mRNA transcripts of GalTase in the OA-fed group may not be due to either a general inhibition of synthesis and/or degradation of mRNAs as revealed by a comparison of the expression of beta-galactoside 2,6 sialyltransferase in both the control and OA-fed groups. The study thus suggests an imbalance in nucleotide pools, such as the one induced by OA, may play a role in the regulation of glycosylation by modulating the glycosyltransferases. PMID- 8508495 TI - Genetic heterogeneity of the excision repair defect associated with trichothiodystrophy. AB - Trichothiodystrophy (TTD) is a rare autosomal recessive disease characterized by brittle hair with reduced sulfur content, mental and physical retardation, a peculiar face and ichthyosis. Photosensitivity has been reported in approximately 20% of the cases in the literature. DNA repair investigations demonstrated that clinical photosensitivity is usually associated with an enhancement of the cellular UV-sensitivity and that the repair defect is in the same gene as in patients from group D of xeroderma pigmentosum (XP). In this paper we describe the characterization of 13 further TTD patients; a defect in the nucleotide excision repair was observed in fibroblast strains from 10 patients, confirming that TTD is frequently associated with DNA repair defects. Genetic analysis based on complementation studies demonstrated the presence of the XP-D defect in seven repair-defective TTD cases, indicating definitively that the concurrence of TTD with XP-D is not a sporadic or casual event. However, three further cell strains (TTD4VI and TTD6VI from two French siblings and TTD1BR from an English patient) showed restoration of normal UV-induced DNA repair synthesis after fusion with XP or TTD cells belonging to XP group D. These observations, which give the first indication that TTD is associated with repair defects behaving differently in the functional test of complementation, suggest some kind of causal connection between defective excision-repair factors and clinical features diagnostic for TTD. A peculiar aspect of TTD in which repair deficiencies are not related to an increased susceptibility to cancer is confirmed also in all the repair-defective TTD patients investigated in this paper. PMID- 8508496 TI - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone tumorigenicity in mouse lung by the synthetic organoselenium compound, 1,4 phenylenebis(methylene)selenocyanate. AB - The chemopreventive effect of 5, 10 and 15 p.p.m. (as selenium) of 1,4 phenylenebis(methylene)selenocyanate (p-XSC) on lung tumor induction by the tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was examined in female A/J mice by administering p-XSC in the diet. Sodium selenite (5 p.p.m. selenium) was given in the same manner for comparison with p-XSC. Mice were fed experimental diets containing the selenium compounds 1 week before i.p. injection of 10 mumol NNK in 0.1 ml saline and throughout the experiment until termination, 16 weeks after carcinogen administration. Body weights of the mice in the different dietary groups did not differ significantly. p-XSC significantly inhibited lung tumor multiplicity from 7.6 tumors per mouse in the control group to 4.1, 3.3 and 1.8 tumors per mouse in animals given 5, 10 and 15 p.p.m. of selenium respectively. In contrast, 5 p.p.m. sodium selenite had no protective effect against lung tumor induction. The results of this study clearly indicate that the structure of selenium-containing compounds is important in determining their efficacy as chemopreventive agents. PMID- 8508497 TI - Genotoxic effects of cyclopenta-fused polycyclic aromatic hydrocarbons in isolated rat hepatocytes and rabbit lung cells. AB - Benz[j]aceanthrylene (B[j]A) and benz[l]aceanthrylene (B[l]A), two isomeric cyclopenta polycyclic aromatic hydrocarbons (CP-PAH) structurally related to 3 methylcholanthrene, were studied with respect to their genotoxic effects in isolated liver and lung cells. Both compounds were found to cause DNA adducts measured by the 32P-postlabelling technique. The level of DNA-adducts in rat hepatocytes exposed to 30 micrograms/ml B[l]A and B[j]A for 4 h were 46.5 +/- 22.0 and 8.3 +/- 5.1 fmol/micrograms DNA respectively. Using butanol extractions, the major and one of the minor B[j]A adducts co-chromatographed with B[j]A-1,2 oxide adducts of 2'-deoxyadenosine and 2'-deoxyguanosine. Thus, oxidation at the cyclopenta-ring of B[j]A appears to be an important activation pathway. In hepatocytes, 3-30 micrograms/ml of B[j]A and B[l]A induced DNA damage and repair measured both as increased alkaline elution of DNA and as increased incorporation of [3H]TdR in the DNA. B[l]A was somewhat more potent than B[j]A in inducing DNA repair. Reactive CP-PAH intermediates formed in the hepatocytes caused mutations in Salmonella typhimurium TA98 upon co-incubation. DNA adducts were also observed in isolated rabbit lung cells exposed to 30 micrograms/ml B[l]A or B[j]A for 2 h. A total of 14.5 +/- 6.9, 2.9 +/- 2.1 and 0.2 +/- 0.6 fmol B[l]A adducts/micrograms DNA were observed in Clara cells, type II pneumocytes and alveolar macrophages respectively. The main B[l]A adduct observed in the liver cells was not found in the lung cells. On the other hand, the levels of B[j]A adducts in the lung cells were in the range 4-14% of that found in liver cells, and no major differences between the various lung cells were observed. Neither B[l]A nor B[j]A induced DNA damage measured by alkaline elution in the lung cells, indicating that these adducts are not alkali labile. PMID- 8508498 TI - Is vitamin E a useful agent to protect against oxy radical-promoted lung tumorigenesis in ddY mice? AB - We have previously reported that oxy radicals can contribute to the enhancing effect of glycerol on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis in ddY mice. In this study, we established that feeding high doses of vitamin E to male ddY mice treated with 4NQO plus glycerol could reduce glycerol-enhanced lung tumorigenesis, due to the inhibition of glycerol-induced oxidative stress on the pulmonary nuclei. At 4 weeks after 4NQO injection (10 mg/kg, s.c.), the levels of nuclear thiobarbituric acid reactive substances and oxidative damage to DNA in the lungs of mice treated with 4NQO plus glycerol (5% solution as drinking water) were significantly higher than those in mice treated with 4NQO. The glycerol-induced increase was completely inhibited when a high vitamin E diet was provided for 4 weeks after 4NQO injection. As previously reported, at 23 weeks after 4NQO administration (at the end of this experiment), the 4 week treatment with glycerol enhanced 4NQO-induced lung tumorigenesis in ddY mice. In contrast, the supply of high doses of vitamin E at 4 and 23 weeks after 4NQO injection suppressed glycerol's ability to enhance lung tumorigenesis. These results suggest that vitamin E is useful in protecting against oxy radical-enhanced lung tumorigenesis in mice. PMID- 8508499 TI - In vitro inhibition of DNA adduct formation by hindered hydroquinols and quinones. AB - A series of thirty-one chemicals (substituted phenols, hydroquinols, quinones and quinoneimines) were investigated as in vitro inhibitors of DNA-benzo[a]pyrene adducts formation. In order to establish the mechanisms by which such compounds may elicit a protective effect at DNA level, the influence of these compounds upon benzo[a]pyrene (BaP) activation by 3-methyl-cholanthrene-stimulated microsomes was also studied. The data obtained suggest that the tested compounds act mainly (but not only) by BaP metabolism inhibition. Several substituted hydroquinols (e.g. 2-methyl-6-tert-butyl-hydroquinol, 2,6-di-isopropyl hydroquinol, 2,3-dimethyl-hydroquinol) and quinones (e.g. 2-methyl-6-tert-butyl 1,4-benzoquinone, 2,6-di-isopropyl-1,4-benzoquinone, 2,3-di-methyl-1,4 benzoquinone) were found to be powerful inhibitors of both BaP metabolism and of BaP-DNA adduct formation (> 95%) at a BaP:inhibitor ratio of 1:10. This effect is significantly stronger than that exerted by the 'classical' BHA or other phenolic antioxidants in similar experimental conditions. Generally, quinones were more active than their corresponding hydroquinols, suggesting that the effectiveness of hydroquinols to prevent DNA adduct formation may be due to their oxidation to quinonic forms. PMID- 8508501 TI - Analysis of mutational specificity induced by heterocyclic amines in the lacZ gene of Escherichia coli. AB - Mutational spectra induced by different heterocyclic amines were characterized and compared with those obtained from diethylnitrosamine and N-methyl-N nitrosourea. Mutation classes were identified by means of a series of mutant lacZ genes in F' episomes in Escherichia coli engineered to detect specifically each of two transitions, four transversions and five kinds of frameshift events. More than 99.5% of the mutations induced by heterocyclic amines were frameshift mutations. -2(C.G-G.C) frameshifts were favored over other types, such as +1(G.C), -1(G.C), +1(A.T) and -1(A.T), except when 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) was administered. -1(G.C) and +1(G.C) frameshifts predominate following Trp-P-1 treatment. A small number of G.C-->T.A transversions were induced by the treatment with 2-amino-3,4-dimethylimidazo[4,5 f]quinoline as well as with several other heterocyclic amines examined. Since G.C ->T.A transversions, but not frameshift mutations, are reported to play a role in heterocyclic amine-induced activation of the c-Ha-ras protooncogene or inactivation of the p53 tumor suppressor gene, the low level of base substitutions, particularly G.C-->T.A transversions, may represent a partial explanation for the relatively modest carcinogenic activity of heterocyclic amines, despite their extraordinarily strong mutagenicity in the Salmonella mutation assay. PMID- 8508500 TI - Measurement and characterization of the denitrosation of tauromustine and related nitrosoureas by glutathione transferases in liver cytosol from various species. AB - The denitrosation of a novel nitrosourea, 1-(2-chloroethyl)-3-[(2 dimethylaminosulfonyl)-ethyl]-1-nitrosoure a, tauromustine (TCNU), has been investigated in liver cytosol from various species and with a pool of cytosolic rat liver glutathione transferases (GSTs). In addition, the denitrosation of related nitrosoureas, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2 chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) have been investigated. By using radioactive nitrosoureas as substrates and HPLC to detect the denitrosated products, a sensitive assay has been developed. The activities towards additional substrates, 1-chloro-2,4-dinitrobenzene (CDNB) and trans-stilbene oxide (tSBO) were also measured in the various cytosol fractions. The apparent Vmax and Km values for the denitrosation of TCNU in rat liver cytosol were calculated to be 830 pmol/min/mg protein and 8.4 mM respectively. The rate of denitrosation of TCNU was found to be highest in the mouse, followed by the rat and the dog. The induction of GSTs by phenobarbital in rats increased the denitrosation of TCNU similar to the activities found towards CDNB and tSBO as substrates. The highest denitrosation activity by GST was determined towards BCNU, followed by CCNU and TCNU. Our results suggest that the denitrosation of various nitrosoureas via GST may play an important role in the deactivating process occurring in vivo and for the efficacy of nitrosoureas used in chemotherapy. PMID- 8508502 TI - Characterization of skin tumor promotion by mirex: structure-activity relationships, sexual dimorphism and presence of Ha-ras mutation. AB - In the present study we have compared the tumor-promoting activity of the non phorbol ester-type skin tumor promoter, mirex, a halogenated cycloalkane pesticide, to the following: (i) chlordane, a halogenated cycloalkane pesticide; (ii) 1,1-bis (4-chlorophenyl)-2,2,2-trichlorethane (DDT), a halogenated bridged aromatic pesticide; and (iii) kepone, a halogenated cycloalkane pesticide, which only differs from mirex by the substitution of two chlorine atoms with an oxygen atom. Topical application of 200 nmol mirex three times weekly for 20 weeks to 7,12-dimethylbenz[a]anthracene (DMBA)-initiated female mouse skin produced approximately 16 tumors/mouse with a 96% incidence of tumor bearing mice. Neither chlordane (2 mumol) or DDT (5 mumol) promoted tumors in DMBA-initiated mouse skin after three times weekly application for 20 weeks. Unexpectedly, DMBA-initiated mice treated with 250 nmol kepone three times weekly for 20 weeks did not develop any tumors, demonstrating that the replacement of two chlorine atoms by an oxygen atom results in loss of the skin tumor-promoting activity of mirex. To further characterize mirex-induced skin tumor promotion, male mice were initiated with a single topical application of 200 nmol DMBA and promoted topically three times weekly for 20 weeks with 200 nmol mirex. As compared to female mice, male mice demonstrated (i) 70% fewer tumors/mouse, (ii) decreased incidence of tumor bearing mice, (iii) increased time to first tumor and (iv) increased latency. To determine the role of ovarian hormones in the increased sensitivity of female mice, mice were initiated with DMBA, ovariectomized (OVX) 2 weeks later and then promoted with mirex. OVX mice exhibited 70% fewer tumors/mouse and a 40% decrease in incidence of tumor-bearing mice as compared to controls. Finally, > 90% of DMBA-initiated/mirex-promoted papillomas from male mice and female mice demonstrated a mutated Ha-ras gene with an A-->T transversion in the middle base of the 61st codon. Collectively, these data indicate that the tumor-promoting ability of mirex is highly structure specific, and ovarian hormones are a factor in the increased sensitivity of female mice to the skin tumor-promoting ability of mirex. Furthermore, mirex appears to clonally expand epidermal cells with a mutated Ha-ras oncogene. PMID- 8508503 TI - Metabolism of nitrofluoranthenes by rat lung subcellular fractions. AB - The nitrofluoranthene (NF) family of compounds includes the potent pulmonary carcinogen 3,9-dinitrofluoranthene (3,9-DNF) and the weak carcinogen 3 nitrofluoranthene (3-NF). Although the specific molecular mechanisms involved in this difference in sensitivity for the induction of lung tumors in rats by 3,9 DNF and 3-NF have not been defined, these compounds most likely induce carcinogenesis by metabolic activation to electrophilic metabolites that bind DNA. The purpose of these investigations was to determine the activation pathways in the rat lung for the metabolism of the di-(3,9-DNF) and mono-nitroisomers (3 NF, 8-NF, 2-NF) of NFs. The metabolic rates of NFs were compared for lung subcellular fractions of pristine rats as well as rats previously treated with 3 methylcholanthrene (3-MC) or phenobarbital at levels that would induce cytochrome P450 enzymes. One major metabolite, the amino derivative, was detected by high pressure liquid chromatography following anaerobic incubation of rat lung cytosol with 3-NF, 8-NF, 2-NF or 3,9-DNF. 3,9-DNF was metabolized to its amino derivative, aminonitrofluoranthene, at a higher rate than 3-NF, 8-NF or 2-NF. Pretreatment of the rats with 3-MC or phenobarbital did not affect the metabolic rates of cytosolic reduction. Both 3-NF and 3,9-DNF were metabolized anaerobically to their amino derivatives by microsomal reductas(s). 3,9-DNF was metabolized twice as fast as 3-NF. The formation of the aminonitrofluoranthene metabolite was increased approximately 2 times with microsomes from 3-MC-induced rats, but was unaffected by microsomes from phenobarbital-treated rats. This suggests that the cytochrome P450 isozymes and reductase, which are induced by 3 MC, may be involved in the metabolism of 3-NF and 3,9-DNF. The metabolic products of 3-NF, formed aerobically, consisted of one major and three minor compounds. The major metabolite, tentatively identified as 3-NF-8-ol, was increased approximately 6 times using microsomes from 3-MC-induced rats. In contrast, 3,9 DNF metabolism was not detected aerobically with lung microsomes. Thus, ring hydroxylation was inhibited in the metabolism of 3,9-DNF, and the major pathway was nitroreduction. This higher rate of anaerobic metabolism of 3,9-DNF over 3-NF and the expected high reactivity of the putative N-acetoxy derivative formed from 3,9-DNF may be responsible for the differential potency for lung cancer induction by these two carcinogens. PMID- 8508504 TI - Structure-activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice. AB - Many arylalkyl isothiocyanates are potent inhibitors of 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in rats and mice. In the mouse, 4-phenylbutyl isothiocyanate (PBITC) and 6-phenylhexyl isothiocyanate (PHITC) exhibited greater inhibition than benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). The present study was conducted to investigate the structure-activity relationships of these four arylalkyl isothiocyanates for their inhibition of NNK oxidation and effects on xenobiotic-metabolizing enzymes in rats and mice. A single dose (0.25 or 1.00 mmol/kg) of each isothiocyanate was given to F344 rats 6 or 24 h before death. The rates of NNK oxidation were decreased in microsomes from the liver, lung and nasal mucosa of rats. Generally, PEITC was more potent than BITC but less potent than PBITC and PHITC. The rates in rat liver microsomes were decreased at 6 h but recovered or increased at 24 h; the rates in rat lung microsomes were markedly decreased at both 6 and 24 h; and the rates in rat nasal mucosa microsomes were also significantly decreased. The same treatment decreased the rat liver N-nitrosodimethylamine demethylase activity dramatically and ethoxyresorufin O-dealkylase and erythromycin N demethylase activities moderately. However, the rat liver microsomal pentoxy resorufin O-dealkylase activity was decreased at 6 h but increased at 24 h, with PEITC showing the most marked induction. The rat liver NAD(P)H:quinone oxidoreductase activity was increased 1.4- to 3.3-fold, with PEITC being most effective; and the glutathione S-transferase activity was increased slightly. Similarly, at a single dose of 0.25 mmol/kg (5 mumol/mouse) 24 h before death, PEITC, PBITC, PHITC but not BITC, decreased NNK oxidation in mouse lung microsomes by 40-85%, with PBITC and PHITC showing greater inhibition. Furthermore, all four isothiocyanates extensively inhibited NNK oxidation in rat lung and nasal mucosa microsomes as well as mouse lung microsomes in vitro, with PEITC (IC50 of 120-300 nM) being more potent than BITC (IC50 of 500-1400 nM) but less potent than PBITC and PHITC (IC50 of 15-180 nM). PHITC was a very potent competitive inhibitor of NNK oxidation in mouse lung microsomes with apparent K(i) values of 11-16 nM. These results indicate that PBITC and PHITC are more potent inhibitors of NNK bioactivation in rats and mice than PEITC. In addition, these arylalkyl isothiocyanates could be effective in protecting against the actions of a broad spectrum of carcinogenic or toxic compounds. PMID- 8508505 TI - Supplemental dietary calcium fails to alter the acute effects of 1,2 dimethylhydrazine on O6-methylguanine, O6-alkylguanine-DNA alkyltransferase and cellular proliferation in the rat colon. AB - Prior studies from our laboratory have demonstrated that K-ras G to A mutations were detectable in a high percentage of carcinomas which developed in the colons of animals treated with the known colonic procarcinogen, 1,2-dimethyl-hydrazine (DMH). Moreover, in this model, the incidence of these mutations was decreased by a supplemental dietary calcium regimen which concomitantly decreased the frequency of rats with multiple tumors as well as tumor size. In an attempt to clarify the possible mechanism(s) involved in this antimutagenic effect of supplemental calcium, two groups of Sprague-Dawley rats were fed semisynthetic diets containing either 0.87 or 1.80% calcium by weight for 3 weeks, s.c. injected with 100 mg/kg of DMH and killed prior to and at various time periods (16-144 h) after injection. The colons of animals were analyzed and compared with respect to O6-methylguanine content in DNA, O6-alkylguanine-DNA alkyltransferase levels as well as cellular proliferation, as assessed by immunohistochemical staining of colonic crypts by bromodeoxyuridine. In certain experiments, these parameters were also analyzed in the proximal and distal colon before and at various times after administration of DMH. The results of these experiments demonstrated that supplemental dietary calcium was not found to influence significantly O6-methylguanine levels, alkyltransferase levels or cellular proliferation in the entire colon or in either colonic segment before or after the acute administration of DMH. DMH did, however, differentially alter all three of these biochemical parameters in the colonic segments (distal > proximal), possibly due to a greater degree of metabolic activation in the distal colon. PMID- 8508506 TI - Examination of alpha-carbonyl derivatives of nitrosodimethylamine and ethylnitrosomethylamine as putative proximate carcinogens. AB - Metabolites produced by enzymic oxidation are believed to be responsible for the mutagenicity and carcinogenicity of N-nitrosamines. Although alpha-hydroxy compounds are often considered, a related and more stable oxidation product, the alpha-carbonyl compound, was studied here. The alpha-carbonyl derivatives of nitrosodimethylamine (NDMA) and ethylnitrosomethylamine (oxidized at either the methyl or the ethyl group) were synthesized. The derivatives were methylnitrosoformamide (MNFA), ethylnitrosoformamide (ENFA) and methylnitrosoacetamide (MNAA). These compounds were then studied as potential toxic, mutagenic and carcinogenic intermediates. All three compounds were very potent directly acting mutagens to Salmonella typhimurium TA1535. Mutational Fingerprints in Escherichia coli of MNFA and ENFA (but not MNAA) matched those produced by SN1-type methylating and ethylating compounds respectively. The latter results indicate that the two alkylnitrosoformamides could be intermediates in the mutagenicity of the parent nitrosamines. In animal studies the putative metabolite MNFA was more acutely toxic than NDMA in F344 rats. In chronic experiments with MNFA in F344 rats and Syrian golden hamsters, tumors of the forestomach were induced by oral administration in most animals (except female hamsters) within 8 months. The properties of these oxidized derivatives of N-nitrosamines are consistent with expectations for proximate carcinogenic intermediates. PMID- 8508507 TI - Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters. AB - Reactive oxygen species (ROS) have been implicated as being involved in tumor promotion processes. However, the mechanism by which ROS modulate tumor promotion has not as yet been elucidated. In this report, we show that phorbol ester-type tumor promoters (12-O-tetradecanoylphorbol-13-acetate [TPA], mezerein and 12-O retinoylphorbol-13-acetate [RPA]), which vary in their in vivo potencies, also differ in their effect on formation of hydrogen peroxide (H2O2) and oxidation of normal bases to 5-hydroxymethyl-2'-deoxyuridine [HMdU] and 8-hydroxyl-2' deoxyguanosine [8-OHdG] in the DNA of SENCAR mouse epidermis, though they are equipotent in causing infiltration of polymorphonuclear leukocytes (PMNs). Treatment of SENCAR mice with the chemopreventive agents (-)-epigallocatechin gallate or tamoxifen (6.5 nmol) prior to application of TPA (6.5 nmol) diminished PMN infiltration, and formation of H2O2, HMdU and 8-OHdG. These results strengthen the evidence that ROS are involved in tumor promotion, and that generation of ROS and the subsequent oxidative DNA modification are related to the tumor-promoting potencies of the different phorbol ester-type promoters. PMID- 8508508 TI - Quantitative analysis of aflatoxin-albumin adducts. AB - Quantitative exposure assessments made using biologically relevant markers will facilitate epidemiological studies of risk from environmental carcinogens. Blood proteins are readily accessible macromolecules that have been shown to be targets for activated chemical carcinogens. Serum albumin is quantitatively the most abundant target for aflatoxin B1 and the measurement of aflatoxin-serum albumin adducts has been used to detect exposed individuals. The goal of these experiments was to devise an analytical procedure that would increase the overall recovery of aflatoxin adducts in serum albumin, and thereby improve the accuracy of exposure monitoring. The method developed consisted of the following procedures. Proteins were precipitated from serum (< or = 100 microliters) with 80% ammonium sulfate, with incubation at 4 degrees C for 2 h. Following dialysis against phosphate-buffered saline (pH 7.0 for 3 h at 4 degrees C), the proteins were digested with protease (Pronase) (1:4.1 w/w enzyme:protein) for 15 h at 37 degrees C with shaking. Enzyme and other undigested proteins were precipitated with acetone (1:2 v/v, 40 min, 4 degrees C). After evaporation of the acetone under vacuum, levels of aflatoxin B1-albumin adducts were determined by radioimmunoassay carried out on 300 microliters fractions. This procedure obviated the isolation of albumin prior to analysis and reduced interference in the radioimmunoassay. High recoveries of aflatoxin B1 adducts were achieved together with a low limit of detection. The applicability of the procedure in epidemiological studies of human aflatoxin exposure was illustrated by results of analysis of aflatoxin-albumin adducts in serum samples from residents of Chongming Island, People's Republic of China. PMID- 8508509 TI - Effects of anticarcinogenic monoterpenes on phase II hepatic metabolizing enzymes. AB - The monocyclic monoterpenoid compounds limonene and sobrerol have anticarcinogenic activity when fed during the initiation stage of dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Here we investigated the potential roles of hepatic glutathione-S-transferase (GST; EC 2.5.1.18) and uridine diphosphoglucuronosyl transferase (UDPGT; EC 2.4.1.17) in monoterpene-mediated chemoprevention. Diets containing the isoeffective anticarcinogenic terpenes, 5% limonene or 1% sobrerol, elevated hepatic GST activity > 2-fold when measured using the general substrate 1-chloro-2,4 dinitrobenzene and 3,4-dichloronitrobenzene for the GST dimer 3-3. However, there were no significant changes in hepatic GST activity when 1,2-epoxy-3-(p nitrophenoxy)propane was used. We found that both terpene diets increased GST affinity-purified protein 1.5-fold and the HPLC subunit profile. Liver GST subunit 3 had the greatest increase followed by 1 and 4 with no change in subunit 2. Both terpene diets significantly increased the activity of the methylcholanthrene-inducible and the phenobarbital-inducible UDPGT isozymes. We propose that much of the anticarcinogenic activity of these monocyclic monoterpenes during the initiation phase of DMBA carcinogenesis is mediated through the induction of the hepatic detoxification enzymes GST and UDPGT. PMID- 8508510 TI - Dietary fat- and phenobarbital-induced alterations in hepatic antioxidant functions of mice. AB - Inbred strains of mice with differential response to known tumor promoters were compared with respect to their susceptibility to modulation of hepatic antioxidant enzymes by long-term treatment with high fat diet (HF) and phenobarbital (PB). Mice of the C57BL/6J (C57), C3H/HeOuJ (C3H) and DBA/2J (DBA) strains were fed diets containing low (5%) or high (15%) amounts of fat (sunflower oil) for 26 weeks from the age of 6 weeks onwards. Groups of mice on the 5% fat diet received 0.05% PB in their drinking water from 12 to 22 weeks of age. Mice of the C57 strain are known to be refractory to promotion of hepatocarcinogenesis, the C3H strain has a high incidence of spontaneous tumors and is sensitive to promotion by HF and PB, and the DBA strain is especially sensitive to promotion by PB. Within all strains of mice, and in both dietary groups, the degree of oxidative stress in the liver was found to increase with age, as was indicated by the increased amounts of TBA reactive material (lipid peroxidation) and decreased glutathione (GSH) and phospholipid contents of the tissue. HF elevated the amount of TBA reactive material in the liver of C57 and C3H mice, induced GSH-peroxidase and Mn-superoxide dismutase activities in the C3H strain, and depressed the hexose monophosphate shunt activity within all mouse strains. PB drastically decreased the amount of TBA reactive material in the liver in all mouse strains, increased catalase activity in all strains and the activity of GSH-peroxidase in the C3H and DBA strains. The above strain differences in responses of hepatic antioxidant functions to HF and PB parallel the differential responsiveness of these mouse strains to promotion of hepatocarcinogenesis by these agents, and the increased antioxidant capacity was proportional to susceptibility to tumor promotion. PMID- 8508511 TI - Aflatoxin M1 in Nepalese sera, quantified by combination of monoclonal antibody immunoaffinity chromatography and enzyme-linked immunosorbent assay. PMID- 8508512 TI - Ethynylestradiol protection against methyl insufficiency in castrated male Wistar/Furth rats fed a methionine-choline-deficient diet. AB - The interactive effects of dietary methyl insufficiency and the estrogenic compound ethynylestradiol (EE) on the levels of S-adenosylmethionine (SAM) and S adenosylhomocysteine (SAH) were examined in the liver, lungs and pancreas of rats. In addition, such effects on the hepatic content of 5-methyl-deoxycytidine (5-MC) in nuclear DNA were determined. Castrated male Wistar/Furth rats were fed various levels of EE in either: (i) a complete, amino acid-defined diet (diet 1); (ii) the same diet lacking in choline and methionine and supplemented with 0.9% of DL-homocystine (equimolar to methionine) (diet 2); or (iii) diet 2 but only with 0.3% DL-homocystine (diet 2M). Methyl deficiency and EE each independently produced decreased weight gains and increased relative liver weights (liver weight relative to total body weight) compared with control animals. Livers from rats fed diets 2 and 2M without EE had lower levels of SAM and lower SAM:SAH ratios than did the livers from diet 1-fed rats not treated with EE. Hepatic SAM:SAH ratios in diet 1-fed rats were not altered by EE treatment. However, EE treatment increased the hepatic contents of SAM and restored the SAM:SAH levels to normal in rats fed diet 2 or 2M. The levels of SAM + SAH in the livers of rats fed the low homocystine diet (diet 2M) were less than in those fed either diet 1 or diet 2. Thus, the addition of EE at 10 p.p.m. gave protection against reduced levels of SAM, and reduced SAM:SAH ratios in the liver, but had little effect when added to the methyl-adequate diet. No differences in hepatic 5-MC levels were observed in any of the groups as a result of either methyl deficiency or EE treatment. Methyl deprivation alone caused no discernible difference in pancreatic SAM levels but did result in a significant rise in SAH levels and thus in decreased SAM:SAH ratios. EE had no consistent effect on pancreatic SAM, SAH or SAM:SAH ratios in any of the diet groups examined. Similarly, the chronic feeding of diet 2, diet 2M or of EE had no significant effect on the SAM contents of lungs, compared with the corresponding levels in control rats. The protection conferred by EE against SAM insufficiency in the livers of rats fed a methionine- and choline-deficient diet is consistent with the relative insensitivity of female rats to the hepatotoxicity of dietary methyl insufficiency. PMID- 8508513 TI - Detection of dopamine--DNA adducts: potential role in Parkinson's disease. AB - Oxidation of catecholamines may lead to the formation of o-semiquinones and o quinones in catecholaminergic brain tissues, and these reactive molecules may form DNA or protein adducts. In this study, cultured cells were treated with dopamine (DA) for 24 h and 32P-postlabelling was used to detect DA-DNA adducts. In HL-60 cells, 250 microM DA induced 8.5 DNA adducts/10(8) nucleotides; adduct formation was dose-dependent up to 500 microM DA. Addition of H2O2 increased the relative adduct levels 7- to 13-fold, but no adducts were detected when DA and ascorbic acid were added simultaneously. In human glioblastoma cell lines U87, U251, SF-763 and SF-767, 1000 microM DA produced 0.98-2.31 adducts/10(8) nucleotides. These results suggest that the formation of DNA adducts by DA may contribute to the development of certain neurodegenerative diseases such as Parkinson's disease. PMID- 8508514 TI - K-ras mutations in benzotrichloride-induced lung tumors of A/J mice. AB - Benzotrichloride (BTC) is used extensively as a chemical intermediate in the synthesis of benzoyl chloride and benzoyl peroxide. Epidemiological data suggest that BTC is a human lung carcinogen. BTC is also a carcinogen in the A/J mouse lung tumor bioassay. Activated K-ras protooncogenes were detected in BTC-induced lung tumors from A/J mice. The polymerase chain reaction was used to amplify specific DNA segments likely to contain activating mutations, and the amplified DNAs were sequenced to identify the mutation. The activating mutation present in the K-ras gene from all BTC-induced lung tumors (24/24) was a GC-->AT transition in codon 12. Thus, BTC may exert its carcinogenic action by activation of the K ras protooncogene through a genotoxic mechanism. PMID- 8508515 TI - Leukocyte-endothelial cell interactions in the liver after hemorrhagic shock in the rat. AB - Leukocyte-endothelial cell interactions in rat livers were investigated using intravital fluorescence microscopy following hemorrhagic shock (MAP at 40 mm Hg for 60 min) and resuscitation. Thirty minutes after resuscitation, when MAP was higher than 100 mm Hg, sinusoidal perfusion was only slightly reduced (>90% of controls). Firm adhesion of leukocytes increased to 370 +/- 54 leukocytes/mm2 after shock and resuscitation compared to control animals (48 +/- 8/mm2; mean +/- SEM; P < .01). Leukocyte-endothelium adhesion was highest in the portal areas and lowest in midzonal and pericentral regions (relationship:2.0: 1.1:1.0). Pretreatment with dexamethasone (5 mg/kg bw) resulted in a dramatic rise of adherent leukocytes following hemorrhagic shock (920 +/- 62/mm2; P < .001). Pretreatment with ibuprofen (15 mg/kg bw) resulted in a similar increase of adherent leukocytes after hemorrhagic shock (750 +/- 60/mm2; P < .001), while pretreatment with MK 886(10 mg/kg), inhibitor of lipoxygenase pathway, reduced leukocyte adhesion slightly (270 +/- 38/mm2). The results reveal that leukotrienes, e.g., released by activated macrophages, are involved in the regulation of leukocyte adhesion in liver sinusoids following hemorrhagic shock and resuscitation. The negative effect of dexamethasone and ibuprofen on hepatic leukocyte adhesion, however, has to be considered for therapeutic use. PMID- 8508516 TI - Protective effect of the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U74006F) on hepatic endothelium in experimental hemorrhagic shock. AB - The effects of the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U74006F) on ultrastructural damage to the hepatic endothelium in a rat model of hemorrhagic shock were examined. Male Sprague-Dawley rats were anesthetized with urethane and subjected to a 2 hr period of hemorrhagic hypotension (mean arterial pressure clamped at 43-45 mm Hg), followed by reinfusion and follow-up for 2 hr. At the end of the experiment, light microscopic analysis of the livers of animals that received an i.v. injection of vehicle (citrate buffer) just prior to reinfusion showed substantial sinusoidal neutrophil influx. Electron microscopic morphometry revealed significant sinusoidal endothelial degeneration. In contrast, rats that received a 10 mg/kg i.v. bolus of U74006F just prior to posthemorrhage reinfusion displayed a significant preservation of endothelial structural integrity. However, this occurred despite the fact that there was the same degree of hepatic neutrophil influx as in the vehicle-treated rats. These results show that U74006F is capable of protecting endothelial structure, even in the face of significant neutrophil invasion, probably via protection from endothelial cell membrane free radical induced lipid peroxidation. PMID- 8508517 TI - Oxygen extraction and vascular dilation are dependently increased in skeletal muscle during canine endotoxemia. AB - The principal aim of these experiments was to evaluate the ability of a skeletal muscle to extract oxygen during endotoxemia, and determine if the decompensatory decrease in skeletal muscle vascular resistance that occurs after exposure to endotoxin is related to muscle oxygen uptake (VO2). A vascularly isolated denervated canine gracilis muscle was perfused in situ at a constant flow (5-7 mL/min/100 g). Endotoxemia was induced by a 30-min intravenous infusion of Escherichia coli endotoxin (2 mg/kg). Perfusion pressure and arteriovenous oxygen difference (a-v O2) were continuously measured, and muscle O2 extraction was calculated (VO2 = flow x a-v O2). These studies found that gracilis muscle oxygen uptake increased from a resting value of 0.30 mL O2/min/100 g to 0.63 mL O2/min/100 g (111% increase) by 90 min post-endotoxin. The arterial conductance (i.e., arterial dilation) increased 58% during this time. The amount of oxygen the muscle extracts was found to be directly related to the degree of vasodilation (r = .97), and inversely correlated to mean arterial pressure (r = .97). Pre-dilating the muscle with sodium nitroprusside did not alter oxygen extraction. However, after the introduction of endotoxin, a pre-dilated muscle increased VO2 94% by 90 min. These observations support the concept that endotoxin causes an increase in VO2 without producing a defect in the ability of muscle to extract oxygen. The vasodilation typically observed in skeletal muscle during endotoxemia is not the cause of the increased oxygen uptake. It seems likely that mediators released by endotoxin metabolically stimulate skeletal muscle cells, which increases oxygen demand, thus promoting vasodilation. PMID- 8508518 TI - Different effects of interleukin-1 on reactivity of arterial vessels isolated from various vascular beds in the rabbit. AB - During septic shock, arterial smooth muscle is thought to be hyporeactive to vasoconstrictors. This hyporeactivity, however, seems to be different from one vascular bed to another. Interleukin-1 (IL-1), which is released during septic shock, might play a role in the different regional vascular responses to norepinephrine. Thus, the aim of the present study was to examine in vitro the effect of IL-1 on the response to norepinephrine of arteries isolated from different territories in the rabbit. Three types of responses were identified: IL 1 decreased NE-induced contraction by 54% in aorta, 42% in carotid artery, 54% in pulmonary artery, and 18% in renal artery; and IL-1 was devoid of significant effect in hepatic and mesenteric arteries; and IL-1 increased NE-induced contraction by 25% in femoral arteries. In conclusion, IL-1 might contribute to the regional blood flow abnormalities during septic shock. PMID- 8508519 TI - Role of angiotensin II in neonatal sepsis. AB - Previous studies in adult animals have indicated that plasma angiotensin converting enzyme (ACE) activity is inhibited by endotoxin. Reduced ACE activity may decrease plasma angiotensin II (AII) levels, contributing to the refractory hypotension we have previously reported in neonatal septic shock. In this study, hemodynamic function, plasma renin activity (PRA), AII, prostacyclin (PGI2), and thromboxane B2 (TxB2) levels were measured in 17-20-day-old dogs before and 1, 2, and 3 hr after endotoxin administration (1 mg/kg, Escherichia coli lipopolysaccharide-B). PRA and AII levels rose significantly 60 min post endotoxin, returning to baseline values by 180 min; PGI2 and thromboxane B2 levels rose post-endotoxin and remained elevated. Indomethacin or captopril was given by oral gavage 30-35 min before endotoxin. Captopril significantly blunted the rise in PRA and AII, while indomethacin blocked the rise in PGI2 and TxB2. Mean arterial blood pressure and cardiac output fell 60 min after endotoxin challenge without pharmacologic intervention and remained depressed. Our data suggest that renin and AII responses to endotoxin challenge remain intact in the neonatal subject. Maintenance of hemodynamics in indomethacin-pretreated dogs may be due to unopposed stimulation of the peripheral vasculature by AII. Thromboxane B2 in maintenance of vasomotor tone may be minimal in the young. PMID- 8508520 TI - Long-term hyperalimentation following hemorrhage/reperfusion injury induces intestinal prostanoid synthesis. AB - Intestinal mucosa and muscularis/serosa prostaglandin (PG) biosynthesis was compared in sham control female rats and rats subjected to mild hemorrhage (hemorrhage to 80 mm Hg for 60 min), blood reperfusion, and maintenance on hyperalimentation (TPN) for 5 days. Tissue PG synthesis was analyzed by radiochromatographic analysis of microsomal membrane fractions prepared from mucosa and muscularis/serosa removed from the duodenum, jejunum, and ileum. Individual PG synthesis in the mucosa and muscularis/serosa sham group was modest, with low levels of synthesis of 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and thromboxane B2. Hemorrhage, reperfusion, and maintenance on TPN for 5 days did not alter PG synthesis in the mucosa, whereas muscularis/serosa synthesis of 6 keto-PGF1 alpha and PGE2 was increased five-fold or more in each tissue studied. These data suggested that the muscularis/serosa could serve as a major source for the elevated PG, previously shown to occur following long-term resuscitation after acute hemorrhage. PMID- 8508521 TI - Alterations in circulating blood volume during polymicrobial sepsis. AB - Although a great deal is known concerning the pathophysiology of sepsis, it is not clear whether circulating blood volume (CBV) is altered under such conditions. To study, this, rats were subjected to sepsis by cecal ligation and puncture (CLP). Immediately after CLP or sham operation, the animals received 3 ml/100 g body weight normal saline subcutaneously. CBV was determined by using in vivo indocyanine green (ICG) clearance at 2, 5, 10, or 20 hr after CLP or sham operation. This technique does not require any blood sampling. Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT) were assayed enzymatically as indicators of hepatocyte damage. Hepatic microcirculation was assessed at a selected time point (10 hr post-CLP) by using laser Doppler flowmetry and colloidal carbon infusion techniques. The results indicate that CBV, as determined by ICG clearance, remained unchanged up to 10 hr following the onset of sepsis (i.e., early sepsis) but decreased significantly at 20 hr after CLP (late sepsis). However, systemic hematocrit increased significantly at 5, 10, and 20 hr after CLP, indicating that plasma volume decreased at those time points. This suggests that there may be limitations in accurately assessing CBV at 5 and 10 hr after CLP, i.e., during the hyperdynamic circulatory state of sepsis, using the ICG clearance method. Moreover, SGPT and SGOT levels increased significantly at 10 hr, and the levels increased further at 20 hr post-CLP. In contrast, microvascular blood flow and carbon-perfused areas in the liver were significantly increased at 10 hr post-CLP. PMID- 8508522 TI - Role of xanthine oxidase and prostaglandins in inflammatory-induced bacterial translocation. AB - We have previously documented that a nonlethal dose of zymosan causes gut mucosal injury associated with increased xanthine oxidase activity and bacterial translocation. The current study was performed to investigate the role of xanthine oxidase activation and other potential mediators of intestinal injury in an LD50 zymosan model. Specific pathogen-free rats and mice were pretreated with saline, allopurinol, or ibuprofen prior to intraperitoneal injection of either saline or the LD50 dose of zymosan. Bacterial translocation to the mesenteric lymph node and systemic organs was measured at 6 or 24 hr following injection. In addition, separate animals in each group were followed for 7 days for survival. Pretreatment with allopurinol or ibuprofen reduced both the incidence and the magnitude of translocation at 6 hr in rats and mice (P < 0.05). In the rats pretreated with allopurinol or ibuprofen, no reduction in the incidence or magnitude of translocation occurred at 24 hr. In the mice pretreated with allopurinol or ibuprofen, although the incidence of translocation was not reduced at 24 hr, the magnitude of translocation was reduced (P < 0.05). Pretreatment with allopurinol or ibuprofen also resulted in an improvement in survival, when compared to zymosan alone (P < 0.01). Allopurinol and ibuprofen provide protection against bacterial translocation and improvement in survival following challenge with a lethal dose of zymosan. PMID- 8508523 TI - Low density lipoprotein subfractions and [Ca2+]i in vascular smooth muscle cells. AB - Several studies have established that plasma low density lipoprotein (LDL) consists of various discrete subfractions. Using a variety of techniques (analytical ultracentrifugation, equilibrium density gradient ultracentrifugation, and gradient gel electrophoresis), LDL has been fractionated into a maximum of seven subclasses that differ in particle size, density, and physiochemical composition. Recently, a predominance of smaller denser LDL particles has been associated with an increased risk of coronary artery disease. However, other lipoprotein changes, such as elevated triglycerides and lower HDL cholesterol levels, have been shown in patients with a predominance of the smaller denser LDL subfractions. Thus, it is unclear whether the enhanced atherogenic potential is induced by the LDL subfraction pattern per se or by concomitant lipoprotein changes. Because intracellular free Ca2+ is an important second messenger involved in atherogenesis and regulation of vascular tone, we studied the influence of three LDL subfractions (very light [LDL1], 1.030 to 1.033 g/mL; light [LDL2], 1.033 to 1.040 g/mL; and dense [LDL3], 1.040 to 1.045 g/mL) on [Ca2+]i in vascular smooth muscle cells (VSMCs) cultured from rat aorta. LDL subfractions were isolated by density gradient ultracentrifugation from human EDTA-plasma (n = 15). [Ca2+]i was measured by fura 2 fluorescence. Basal [Ca2+]i was 77 +/- 6 nmol/L. Stimulation of VSMCs with dense LDL3 caused a significantly (P < .05) more pronounced increase (+71 +/- 13 nmol/L) compared with LDL1 (+38 +/ 8 nmol/L) and LDL2 (+36 +/- 9 nmol/L). To further investigate the mechanisms leading to the stimulation of [Ca2+]i by LDL subfractions, we incubated VSMCs with the Ca2+ antagonists nifedipine, diltiazem, and verapamil in concentrations up to 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508524 TI - Cellular mechanisms of endotoxin-induced myocardial depression in rabbits. AB - We investigated the mechanisms by which endotoxic shock induces intrinsic myocardial depression by studying cardiac myocytes isolated from 10 anesthetized instrumented rabbits given 172 +/- 42 (mean +/- SD) micrograms/kg IV endotoxin. Left ventricular (LV) depression developed 4 +/- 1 hours after endotoxin administration, with a 15 +/- 4% increase in LV internal end-systolic diameter, measured with sonomicrometers at a matched LV end-systolic pressure of 65 +/- 10 mm Hg. Normal LV pressure, arterial PO2, and pH were maintained to minimize confounding effects of ischemia, hypoxia, and acidosis. Cardiac myocytes from endotoxin-exposed rabbits had less unloaded cell shortening and lower peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) at [Ca2+] levels ranging from 0.5 to 16 mM when compared with myocytes isolated from normal rabbits or rabbits undergoing an identical protocol but without exposure to endotoxin. At 2 mM [Ca2+], cell shortening was depressed by approximately 25% because of a decrease in action potential duration (207 +/- 70 versus 375 +/- 64 milliseconds). In contrast, there was only mild impairment of sarcoplasmic reticulum (SR) function. When myocytes were restimulated after rest periods of 4 to 480 seconds, the decrement in cell shortening (rest decay), peak -dL/dt and peak +dL/dt, and the recovery from rest decay were similar in myocytes from endotoxin-treated and normal rabbits. There was a greater decrement in cell shortening in the second beat of postrest recovery in myocytes from endotoxin treated rabbits than in normal myocytes. This was partly due to a 12% decrement in action potential duration with rest decay, which did not occur in normal myocytes. The SR Ca2+ content assessed by contractures in 10 mM caffeine was similar in the two groups. We conclude that endotoxic shock produces a LV depression in vivo that persists in isolated myocytes studied in vitro. This intrinsic myocardial depression is largely related to endotoxin-mediated sarcolemmal alterations, which shorten action potential duration, and is not due to alterations in SR function. PMID- 8508525 TI - Rat atrial myocyte plasmalemmal caveolae in situ. Reversible experimental increases in caveolar size and in surface density of caveolar necks. AB - The structure, size, and surface density of the conspicuous flask-shaped structures called caveolae that are located under the plasma membrane of cardiac myocytes in intact rat atria were studied by electron microscopy after physiological perturbations designed to examine whether caveolae and/or their necks are fixed or mobile and whether the caveolar lumen is always open or can close off from the interstitial space. We showed that, in stretched and unstretched atria, horseradish peroxidase could enter or be washed out of caveolae at 37 degrees, 18 degrees, and 4 degrees C, but this finding does not rule out that caveolae and/or their necks can cycle rapidly between states closed and open to the interstitial space. Electron microscopy of thin sections revealed that exposure of atria at 37 degrees or 18 degrees C to physiological salt solutions made hypertonic by adding 150 mM sucrose or mannitol resulted in a striking enlargement of caveolar profiles within 1 to 5 minutes. Caveolar enlargement was rapidly reversible on return to control saline. After freeze fracture of atria exposed to these hypertonic solutions, quantitative analysis of electron micrographs of the fracture faces revealed statistically significant increases in cross-sectional diameter of cross-fractured caveolar necks and in mean number of caveolar necks penetrating per unit area of plasmalemmal fracture face. These results suggest that atrial myocyte caveolae are dynamic structures whose necks may be reversibly inserted into and withdrawn from the plasmalemma, possibly (but not necessarily) corresponding to states in which caveolae are, respectively, open and closed to the interstitial spaces. PMID- 8508526 TI - Evidence for sensory nerve involvement in cutaneous reactive hyperemia in humans. AB - To study the involvement of local sensory nerves in reactive hyperemia, laser Doppler measurements of skin blood flow were recorded in locally anesthetized and untreated forearm sites in eight volunteers after 90, 180, and 360 seconds of arrested forearm blood flow. The reactive hyperemia increased in magnitude and duration in response to increasing occlusion periods. However, maximum postocclusion flows in the untreated site of 31 +/- 5%, 38 +/- 6%, and 49 +/- 5% (mean +/- SEM) flux were significantly greater than the 14 +/- 3% (P < .005), 20 +/- 4% (P < .005), and 25 +/- 5% (P < .001) flux seen in the anesthetized sites. The duration of the hyperemia was also shortened from 139 +/- 26 seconds in the untreated site to 61 +/- 17 seconds (after the 360-second occlusion, P < .02) in the anesthetized sites. The anesthesia did not alter the increase in local blood flow induced by intradermally injected calcitonin gene-related peptide. Topically applied capsaicin induced a localized increase in blood flow that was unaffected by anesthesia and a surrounding flare that was abolished by the treatment. The results show that local anesthesia can significantly inhibit reactive hyperemia by a mechanism that does not alter the vasodilation induced by exogenous calcitonin gene-related peptide or the localized capsaicin-induced release of vasodilators from sensory nerves. Indomethacin was also found to be effective in suppressing reactive hyperemia. The evidence suggests that postocclusion reactive hyperemia in human forearm skin is mediated by a local reflex involving sensory nerves and a cyclooxygenase product, probably a vasodilator prostaglandin. PMID- 8508527 TI - Regulation of capillary perfusion by small arterioles is spatially organized. AB - To explore a mechanism for spatial recruitment of capillaries, this study determined whether the arterioles controlling capillary perfusion, which typically arise as sequential branches along a transverse arteriole, could respond differently from each other in situ in a spatially ordered way. Diameter changes were measured for these arterioles at a known location in the intact microvasculature in the cremaster muscle of anesthetized Golden hamsters (N = 67); each arteriole controls separate capillary groups. These arterioles all had the same concentration dependence to locally (by micropipette) applied norepinephrine (NE, 10(-9) to 10(-3) mol/L), and 10(-9) mol/L NE did not induce diameter changes when applied locally to individual vessels. However, 10(-9) mol/L NE added to the tissue superfusate, or 5% added superfusate oxygen (also locally subthreshold), each induced significant diameter changes (both constrictions and dilations), in different branches, that were presumably due to summation of individually subthreshold events that changed the prevailing conditions at the point of observation. These significant diameter changes were related to the maximal diameter or to initial tone of the branches, but these changes occurred in different ways for NE versus oxygen. With NE, the branch arterioles that constricted (versus dilated) were significantly larger (maximal diameter, 22.3 +/- 2.6 versus 15.9 +/- 2.1 microns) and had higher tone (fractional constriction, 0.53 +/- 0.05 versus 0.63 +/- 0.05); with oxygen, those that constricted were the same size as those that dilated (maximal diameter, 28.6 +/- 1.1 versus 30.5 +/- 2.7 microns), but constrictors had lower tone (fractional constriction, 0.49 +/- 0.04 versus 0.39 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508528 TI - Contractile activity modulates actin synthesis and turnover in cultured neonatal rat heart cells. AB - In this study, the role that active tension development plays in the formation and maintenance of cardiac myocyte myofibrillar structure and cellular shape was investigated. By use of the calcium channel blocker verapamil, spontaneous contractile activity of neonatal rat heart myocytes was inhibited for 24 to 96 hours. Confocal microscopy of rhodamine phalloidin-stained cells revealed that, within 24 hours of contractile arrest, actin filaments of myofibrils were no longer aligned with one another at their I bands and Z lines. Cellular shape was also affected, with the cells developing a less stellate appearance while remaining attached to the substrate as well as to one another. By 48 hours, actin fibrils were largely absent from these cells. The disappearance of actin was confirmed by measurements of actin synthesis and accumulation rates and by pulse chase biosynthetic labeling experiments. It was revealed that, although actin synthesis was significantly reduced in arrested myocytes, the rapid disappearance of total cellular actin was largely due to increased rates of actin degradation. Contractile arrest produced by L-type calcium channel blockade with verapamil (or other calcium channel blockers) accelerated actin degradation to a greater extent than K+ depolarization. Chloroquine partially suppressed the accelerated rate of actin degradation, indicating that lysosomal proteolysis may be involved in actin degradative processing. Protein kinase C activation also partially inhibited the accelerated rate of actin degradation but did not restore actin filaments in arrested myocytes. The reformation of actin fibrils and their reassembly into striated myofibrils occurred when contractile activity was restored by removal of verapamil from the culture medium. The period of time required for myocytes to reassemble actin filaments and to regain their elongated morphology was proportional to the period of time that the cells were inhibited from contracting. Data are presented to indicate that active tension development by neonatal cardiac myocytes in culture is critical to the maintenance of filamentous actin structure via mechanisms involving actin assembly, disassembly, and degradation. PMID- 8508529 TI - Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. AB - Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase in beta-myosin heavy chain mRNA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8 week LVH, 20-week nonfailed LVH, 20-week failed LVH) when compared with appropriate age-matched control groups. In contrast, Ca(2+)-ATPase mRNA levels were decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with cardiac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is associated with a selective reinduction of the fetal gene program, which persists even after the development of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508530 TI - Isolation of gene markers of differentiated and proliferating vascular smooth muscle cells. AB - To isolate specific markers of both differentiated and proliferating vascular smooth muscle cells (VSMCs), we used the technique of differential cDNA screening using RNA from cultured rat aortic VSMCs. The tissue specificity of expression of all of the cDNAs isolated was determined by Northern analysis. We isolated seven distinct cDNAs that were more strongly expressed in freshly dispersed, differentiated, aortic VSMCs compared with dedifferentiated late-passage cells. These were the cDNAs for tropoelastin, a matrix protein; alpha-smooth muscle (SM) actin, gamma-SM actin, calponin, and phospholamban, which are all proteins associated with the contractile function of differentiated VSMCs; SM22 alpha, a smooth muscle-specific protein of unknown function, and CHIP28, a putative membrane channel protein that is not highly expressed in other SM tissues and may therefore be a new VSMC marker. Two cDNAs that were expressed preferentially in late-passage dedifferentiated VSMCs were also isolated. These were the cDNAs for osteopontin and matrix Gla protein (MGP). Like CHIP28, MGP was strongly expressed in aortic VSMCs but not in other types of tissues containing SM cells, suggesting that both have specific functions in vascular tissue. Osteopontin and MGP have both previously been isolated from developing bone. Their expression in proliferating VSMCs suggests that they may be involved in regulating the calcification that commonly occurs in vascular lesions. The set of cDNAs obtained extends the range of DNA probes that are available for identifying VSMCs and characterizing their phenotype in vivo by in situ hybridization. Therefore, they should aid in the analysis of gene expression during the development of vessel lesions. PMID- 8508531 TI - Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. AB - In human myocardium, the nature of the K+ currents mediating repolarization of the action potential is still speculative. Delayed rectifier channels have recently been cloned from human myocardium, but it is unclear whether or not these currents are involved in the termination of the cardiac action potential plateau. In intact human atrial myocytes, we have identified a rapid delayed rectifier K+ current with properties and kinetics identical to those expressed by a K+ channel clone (fHK) isolated from human heart and stably incorporated into a human cell line for the first time. The myocyte current amplitude was 3.6 +/- 0.2 pA/pF (at +20 mV, n = 15) and activated with a time constant of 13.1 +/- 2 milliseconds at 0 mV (n = 15). The half-activation potential (V0.5) was -6 +/- 2.5 mV (n = 10) with a slope factor (k) of 8.6 +/- 2.2 (n = 10). The heterologously expressed fHK current amplitude was 136 pA/pF (at +20 mV, n = 9) with an activation time constant of 11.8 +/- 4.6 milliseconds at 0 mV; V0.5 was 4.1 +/- 2.4 mV (mean +/- SEM, n = 8); and k was 7.0. The conductance of single fHK channels was 16.9 picosiemens in 5 mM bath K+. Both native and cloned channel currents inactivated partially during sustained depolarizing pulses. Both currents were blocked by micromolar concentrations of 4-aminopyridine and were relatively insensitive to tetraethylammonium ions and class III antiarrhythmic agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508532 TI - Gene targeting. The precise manipulation of the mammalian genome. AB - Genetics is a powerful tool for studying the function of different gene products as well as the physiological consequences of a normal or aberrant polypeptide. Until recently, the most powerful genetic applications have been restricted to relatively simple organisms whose genomes are more easily manipulated. For a number of years, in lower organisms, it has been possible to create defined genetic changes that are targeted to a specific locus or even to a defined codon or transcriptional regulatory sequence. With the development of gene targeting using embryonic stem cells derived from the preimplantation blastocyst of a mouse, it has become possible to extend these experiments to a mammalian system. Via homologous recombination, one can ablate, or "knock out," a defined genetic locus or mutate a particular set of nucleotides that encodes a peptide domain of interest. These techniques, when applied to genes that underlie normal cardiovascular function, promise to define the exact role(s) different proteins play during the development, growth, and maintenance of the heart. The ability to generate defined animal models of human disease in which the primary genetic defect is known should lead to fundamental advances in the study of the normal and failing heart. PMID- 8508533 TI - Crossbridge scheme and the kinetic constants of elementary steps deduced from chemically skinned papillary and trabecular muscles of the ferret. AB - Elementary steps of the crossbridge cycle in chemically skinned ferret myocardium were investigated with sinusoidal analysis. The muscle preparations were activated at pCa 4.82 and an ionic strength of 200 mM, and the effects of the change in the MgATP (S) and phosphate (Pi) concentrations on three exponential processes were studied at 20 degrees C. Results are consistent with the following crossbridge scheme: [formula: see text] where A is actin, M is myosin, D is MgADP, and Det includes all detached states (MS and MDP) and weakly attached states (AMS and AMDP). From our studies, we obtained K1a = 0.99 mM-1 (MgATP association), k1b = 270 s-1 (ATP isomerization), k-1b = 280 s-1 (reverse isomerization), K1b = k1b/k-1b = 0.95, k2 = 48 s-1 (crossbridge detachment), k-2 = 14 s-1 (reverse detachment), K2 = 3.5, k4 = 11 s-1 (crossbridge attachment), k 4 = 107 s-1 (reverse attachment), K4 = 0.11, and K5 = 0.06 mM-1 (Pi association). K6 is the rate-limiting step, and it is the slowest forward reaction in the cycle, which results in the rigor-like AM state. K1a (MgATP binding) is four times that of rabbit psoas, and K5 (Pi binding) is 0.3 times that of psoas, demonstrating that crossbridges in myocardium bind MgATP more and Pi less than psoas. The rate constants of ATP isomerization (k1b, k-1b), crossbridge detachment (k2, k-2), and crossbridge attachment (k4) steps are generally an order of magnitude slower than rabbit psoas. The reverse attachment step (k-4) is similar to that in psoas, indicating that this step may occur irrespective of the myosin type and possibly spontaneously. The above scheme with the deduced kinetic constants predicts the following crossbridge distributions at 5 mM MgATP2- and 8 mM Pi:AM (3%), AM S (15%), AM*S (14%), Det (50%), AM*DP (6%), and AM*D (12%). The actual number of attached crossbridges was measured to be 51 +/- 4% by the stiffness ratio during activation and after rigor induction, and a strong correlation was seen with the prediction. Our results are consistent with the hypothesis that force generation occurs at the Det-->AM*DPi transition, and the same force is maintained after the release of Pi. PMID- 8508534 TI - Differential effects of the optical isomers of EMD 53998 on contraction and cytoplasmic Ca2+ in isolated ferret cardiac muscle. AB - EMD 53998 (a thiadiazinone) is a novel inotropic substance that increases the Ca2+ sensitivity of the myofilaments in skinned cardiac fibers and has been found to have similar effects in intact cardiac muscle. However, the compound also possesses the ability to inhibit phosphodiesterase III, indicating that its actions in intact cardiac muscle are likely to be complex. The present study was carried out to investigate the possibility that the optical isomers of EMD 53998- (+)EMD 57033 and (-)EMD 57439--which have recently been shown to possess a separation of sensitization and phosphodiesterase inhibition in subcellular preparations, might also demonstrate this separation of activities in intact cardiac muscle. The experiments were performed on isolated ferret papillary muscles, which were contracting isometrically. In some preparations, the photoprotein aequorin was injected into superficial cells to measure intracellular Ca2+ as well as force. (+)EMD 57033 caused a substantial positive inotropic effect that was associated with prolongation of the twitch, reduction in the amplitude of the Ca2+ transient, and abbreviation of the Ca2+ transient. This is the profile expected of a Ca(2+)-sensitizing compound. Conversely, (-)EMD 57439 caused a less marked positive inotropic effect that was associated with an abbreviation of the twitch, an increase in the amplitude of the Ca2+ transient, and an abbreviation of the Ca2+ transient. This is the profile expected of an agent producing its inotropic effect by increasing cAMP (e.g., phosphodiesterase inhibition). The results indicate that the optical isomers of EMD 53998 possess a remarkable separation of Ca(2+)-sensitizing and phosphodiesterase-inhibiting activities in intact cardiac muscle. These actions were additive and could account for the effects observed with EMD 53998. (+)EMD 57033 appears to be the first inotropic agent that acts predominantly by increasing myofilament calcium sensitivity. PMID- 8508535 TI - Cyclooxygenase-dependent vasoconstrictor alters vascular function in the vitamin E-deprived rat. AB - We tested the hypothesis that increased production of lipid peroxides, mediated by a dietary vitamin E deprivation, would alter the cyclooxygenase pathway of arachidonate metabolism, resulting in impaired endothelium-dependent vascular function. Mesenteric arteries from control (n = 12) and vitamin E-deprived (n = 12) Sprague-Dawley rats were studied in a myograph. Endothelium-dependent relaxations to methacholine were similar in the arteries from vitamin E-deprived rats compared with control arteries (EC50, 0.057 +/- 0.006 versus 0.065 +/- 0.009 microM). However, in the arteries from the vitamin E-deprived rats, this response was potentiated in the presence of a cyclooxygenase inhibitor (1 microM meclofenamate; EC50, 0.035 +/- 0.003 versus 0.057 +/- 0.006 microM; P < .05) or thromboxane A2/prostaglandin H2 receptor blocker (1 microM SQ 29548; EC50 0.029 +/- 0.002 versus 0.057 +/- 0.006 microM; P < .05) but had no effect on the arteries from the control rats. Endothelium-independent relaxations to sodium nitroprusside were not effected by vitamin E deprivation. Arachidonic acid increased tension twofold more in the arteries from the vitamin E-deprived rats compared with the control rats (at 1 microM; 0.43 +/- 0.05 versus 0.23 +/- 0.03 mN/mm; P < .05). The enhanced vasoconstriction was blunted, and the group difference was eliminated by a cyclooxygenase inhibitor (0.15 +/- 0.02 versus 0.43 +/- 0.05 mN/mm, P < .05) or a thromboxane A2/prostaglandin H2 receptor blocker (0.17 +/- 0.04 versus 0.43 +/- 0.05 mN/mm, P < .05). Prostaglandin endoperoxide synthase expression, determined by Western immunoblotting on aortas from the same rats, was increased in the vitamin E-deprived rats (3.14 +/- 0.8 versus 1.06 +/- 0.4 fmol/ng DNA, P < .05). In summary, mesenteric arteries from the vitamin E-deprived rats demonstrated altered endothelium-dependent responses that were in part due to a cyclooxygenase-dependent vasoconstrictor binding to the thromboxane A2/prostaglandin H2 receptor. In the aorta, there was an associative increase in the expression of prostaglandin endoperoxide synthase. We speculate that, in some vascular diseases, increased lipid peroxidation may influence endothelium-dependent vascular function by modulating the cyclooxygenase pathway of arachidonate metabolism. PMID- 8508536 TI - Myotrophin in human cardiomyopathic heart. AB - Earlier, myotrophin, a factor, has been isolated, purified, and partially sequenced from spontaneously hypertensive rat hearts that stimulated myocyte growth. To evaluate the role of myotrophin in the initiation of the human dilated cardiomyopathic heart, we have isolated and purified myotrophin to homogeneity (approximately 50,000-fold) as defined by reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). During purification, we used a bioassay system in which adult myocardial cells maintained in culture were used to evaluate protein synthesis by the incorporation of [3H]leucine into myocyte protein. Myotrophin purified from human dilated cardiomyopathic hearts is composed of a single polypeptide chain having an apparent molecular mass of 12 kD, determined by SDS-PAGE. The partial internal amino acid sequence of human myotrophin is very similar to that of rat myotrophin peptide T9. Using a rat myotrophin peptide (T26) antibody, we identified human myotrophin on an immunoblot. These results showed that human myotrophin possesses the T9 and T26 regions of rat myotrophin. Human myotrophin stimulated myocardial protein synthesis and cell growth, similar to the way in which rat myotrophin stimulated these factors. Western blot analysis showed the presence of myotrophin in both dilated cardiomyopathic and normal human hearts. In addition, we observed significantly elevated levels of myotrophin in dilated cardiomyopathic human hearts when compared with age- and sex-matched normal control hearts. From these observations, we conclude that myotrophin is present in normal human hearts, is found at higher levels in dilated cardiomyopathic human hearts, and may play a role in the initiation of cardiac hypertrophy as well as in normal growth of cardiac myocytes in humans. PMID- 8508537 TI - Balloon dilatation of the pharynx. AB - Balloon dilatation has become a widely accepted technique in the management of oesophageal and other gastrointestinal strictures. The use of this procedure in the pharynx has rarely been reported. We have performed 55 balloon dilatations on 13 patients with pharyngeal strictures. In three patients all symptoms were permanently abolished after one dilatation. Seven patients were successfully managed with repeated, regular dilatations. Two patients had a good initial response but this was not maintained and one patient had no relief of symptoms. Balloon dilatation is minimally invasive, less traumatic than rigid pharyngoscopy with dilatation, and well tolerated. It may be frequently repeated, and has successfully relieved dysphagia caused by benign and malignant strictures of the pharynx, including instances where previous rigid bouginage had failed. PMID- 8508538 TI - Considerations of cochlear implant surgery. AB - Although cochlear implants have been reported to be easy to perform, some difficulties have been experienced in 4 of 21 operations. In order to make this surgery easier, the following points should be considered. Pre-operative CT and MRI must be performed in order to determine the condition of the cochlea. To determine the condition of the round window, exploratory tympanotomy is recommended in some cases. After insertion of the electrode in the cochlea, a radiograph should be taken during the operation to confirm that the electrode is correctly positioned. PMID- 8508539 TI - Battery acid burns of the upper gastro-intestinal tract. AB - Strong acid ingestion produces distinctly different injuries from alkali burns. Alkali burns are well described but the lack of literature on the diagnosis and management of acid burns is apparent. This retrospective review of 18 patients with battery acid (30% sulphuric acid) ingestion showed no correlation between the severity of the symptomatology and the degree of injury. The quantity of acid needed to cause a significant upper GIT burn was more than 200 ml. Previous reports that acid spared the oesophagus due to rapid transit were disproved, since oesophageal involvement was found in 55% (10/18). Deep burns rather than circumferential burns resulted in stricture formation. The major injury site was the gastric antrum with 4 patients (23%) requiring surgical intervention to restore function. PMID- 8508540 TI - An audit of the complications of paediatric tonsillectomy, adenoidectomy and adenotonsillectomy. AB - Tonsillectomy, adenoidectomy and adenotonsillectomy are among the commonest surgical procedures undertaken in children. The notes of 413 consecutive children having tonsillectomy, adenoidectomy or adenotonsillectomy were analysed retrospectively to determine complication rates. Of the total number of children, 5.6% had at least one complication, the most common of which was haemorrhage occurring as a first complication in 3.9% (16 children). Three children with bleeding required active treatment (0.7%), one requiring transfusion and two requiring a return to theatre, all within 3 1/2 hours of operation. The incidence of reactionary bleeding was not associated with the grade or seniority of the surgeon. Six children (1.5%) developed a fever post-operatively, of which one required antibiotic treatment. On the basis of these results it is feasible for such procedures to be carried out on a day-care basis. PMID- 8508541 TI - Haemorrhagic nasal nodules. AB - Haemorrhagic nodules have been mentioned previously as a significant cause of epistaxis in adults. We have taken photographs and obtained biopsies to characterize them. They consist of an aneurysmal dilatation of an unusually sited muscular artery with evidence of hypertensive changes in the wall, and thrombus and haemorrhage into the adjacent connective tissue. PMID- 8508542 TI - Mean airflow rates in laryngeal polyposis. AB - This study assesses the laryngeal airflow characteristics in 10 patients with laryngeal polyposis before and after surgical excision. The results indicate that mean airflow rates in the presence of polyps are a reflection of two mechanical processes. Narrow based polyps splint the glottis open during phonation, thus increasing flow rates, whereas large broader based polyps tend to obstruct the glottis and reduce the airflow. The results suggest that mean airflow rates may be used to measure the improvement in laryngeal function following surgical intervention in individual patients. PMID- 8508543 TI - Open structure rhinoplasty. AB - Open structure rhinoplasty (OSR) uses the open or external approach via a mid columellar and bilateral marginal incision. In combination with grafting procedures, such as columellar struts, dorsal grafts and tip grafts, rhinoplasty has developed from a merely reductive procedure to a more graduated approach to the nose. Emphasis is now placed on repositioning, augmentation and restructuring the nasal anatomy to create as natural and functional a nose as possible. This retrospective study analyses our experience with 130 rhinoplasties over a 3-year period. The study reveals OSR to be a safe and reliable technique which produces predictable results. PMID- 8508544 TI - Middle meatal antrostomy: long-term patency and results in chronic maxillary sinusitis. A prospective study. AB - This prospective study included 51 patients with chronic maxillary sinusitis who had 90 middle meatal antrostomy procedures. The aim of the study was to examine the long-term patency of the antrostomy 18-30 months post-operatively (average 26 months) and the relationship between the degree of patency and the degree of improvement in each of the symptoms of chronic maxillary sinusitis. Our results showed patency as follows: 80% widely patent (more than 8 mm), 9% patent (5-8 mm), 4.5% stenosed (less than 5 mm), 6.5% blocked by mucosal disease and none were closed by bone. For all symptoms, there was a significant relationship between the degree of patency and the degree of improvement (P < 0.01 for headache, nasal obstruction and pain, P < 0.05 for post-nasal discharge). We conclude from this study that middle meatal antrostomy has a long-term high patency rate and there is a significant relationship between the degree of patency and the degree of improvement in each of the symptoms of chronic maxillary sinusitis. PMID- 8508545 TI - Changes in nasal mucosal blood flux and air-flow resistance on unilateral histamine challenge. AB - To investigate reflex vascular control in the nose, we challenged each side of the nose with 0.9% saline and histamine (0.3 mg aqueous) and observed changes in unilateral nasal airway resistance (Rnaw) and laser doppler flux (LDF) in response to contra-lateral and ipsilateral challenge in eight normal subjects. Preliminary studies demonstrated that the preferred site for observation of LDF was the nasal septum (same-day concordance 0.920; inferior turbinate 0.307). Ipsilateral contra-lateral saline induced no significant change to either parameter. Ipsilateral histamine produced a highly significant rise in LDF (757 arbitrary units SEM 94 at 3 min; baseline 489 SEM 75: P < 0.05) and Rnaw (baseline: 3.10, SEM 0.52; 5 min: 8.81, SEM 2.09 cmH2O/l/s: P < 0.01). Contra lateral histamine produced a significant P < 0.05) fall in both (LDF 317, SEM 24 at 3 min; Rnaw 2.67, SEM 0.78 cm H2O/l/s at 6 min). This previously unrecorded observation suggests a neural reflex that increases the patency of the contra lateral nostril after unilateral obstruction is provoked. PMID- 8508546 TI - Changing the indwelling Provox tracheoesophageal voice prosthesis as an out patient procedure. AB - The use of the indwelling tracheo-oesophageal prosthesis is gaining popularity for vocal rehabilitation after laryngectomy. These devices can often provide trouble-free phonation for many months before they become incompetent or require increased effort to open them. When this occurs changing the defective valve for a new one is required. We describe simplification of the technique described by the manufactures which is eminently suitable for use as an out-patient procedure under local anaesthesia. PMID- 8508547 TI - A prospective study of otitis externa. PMID- 8508548 TI - The Intercollegiate Assessment--'the Third Part'. PMID- 8508549 TI - Ploidy status and the response of T1 glottic carcinoma to radiotherapy. AB - Flow cytometric DNA ploidy measurements were performed on formalin fixed paraffin embedded tumour specimens from patients with a T1 glottic laryngeal carcinoma in order to evaluate the role of DNA content in relation to local control. From 1980 to 1987, a consecutive series of 90 patients with a T1 glottic laryngeal carcinoma were treated by radiotherapy with curative intent. Biopsies from 44 of these patients were readily available for DNA flow cytometry. In this group aneuploidy was associated with a significantly higher risk (P = 0.018) of local recurrence within 2 years after completion of radiotherapy (38% vs. 9% in the diploid group). PMID- 8508550 TI - Teaching nontraditional nursing students--adult learners. PMID- 8508551 TI - Student ethics. PMID- 8508552 TI - Cyclosporin A in paediatric rheumatology. PMID- 8508553 TI - How to measure health status in rheumatoid arthritis in non-English speaking patients: validation of a Spanish version of the Health Assessment Questionnaire Disability Index (Spanish HAQ-DI). AB - The HAQ-Disability Index (HAQ-DI) is a useful instrument to measure health status in rheumatoid arthritis (RA) patients. Translation into another language requires a validation process, however. We have translated the HAQ-DI to be used on Spanish-speaking populations. We administered the questionnaire to 97 RA patients during the course of routine medical care. Reliability, measured by a test-retest with a one-month interval, was high (Spearman's rho = 0.89). Convergent and construct validity was obtained for all comparisons (Pearson's r > 0.4). The instrument was sensitive in detecting clinical improvement. We conclude that the Spanish HAQ-DI retains the characteristics of the original index and can be used to assess outcome in Spanish-speaking patients with RA. The procedure described may be used to translate the instrument into other languages either directly from English or from the Spanish version presented here. PMID- 8508554 TI - The Italian version of the Functional Disability Index of the Health Assessment Questionnaire. A reliable instrument for multicenter studies on rheumatoid arthritis. AB - A working group of ten rheumatology institutes (UNIREUM) was formed in Italy to promote multicenter therapeutic studies on rheumatoid arthritis. The Functional Disability Index (FDI) of the Health Assessment Questionnaire (HAQ) was chosen as a measure of disability. This paper reports the results of a multicenter study to validate an Italian translation of the instrument and to assess its reliability and validity. Two questions were modified to achieve cross-cultural equivalence. Back-translation into English showed agreement with the American instrument. Reproducibility was high: the test-retest correlation coefficient was 0.989 and ranged from 0.81 to 0.99 for the centers taken separately. Validity was confirmed by a correlation coefficient of 0.95 between the patient self-attributed and the physician-attributed FDI scores. We conclude that our Italian version of the HAQ FDI is a reliable and valid self-administered instrument. PMID- 8508555 TI - IgM rheumatoid factor and the inhibition of covalent binding of C4b to IgG in immune complexes. AB - Work by other investigators has shown that IgM-rheumatoid factors (IgM-RF's) can impede complement-mediated inhibition of immune precipitation. We examined the binding of complement component C4b to radiolabelled IgG in model immune complexes and demonstrate that IgM-RF's are capable of reducing the covalent binding of C4b to 125I-IgG in the complexes. Reduced binding to IgG, however, may not be accompanied by binding of C4b to IgM-RF's within the complex, as we also demonstrate that IgM-RF's are relatively poor at C4b capture compared with normal IgM. PMID- 8508556 TI - Prednisone and piroxicam for treatment of primary Sjogren's syndrome. AB - Primary Sjogren's syndrome is a systemic autoimmune exocrinopathy characterized by a lymphoplasmacytic infiltrate and destruction of salivary and lacrimal glandular tissues. There is no widely accepted or effective systemic therapy for this disorder. The purpose of this 6-month randomized, double-blinded, placebo controlled study was to examine the effects of prednisone (30 mg, alternate days), piroxicam (20 mg, daily), or placebo on the salivary, lacrimal and immunologic alterations of primary Sjogren's syndrome. Eight patients were enrolled in each group. Salivary and lacrimal function were assessed at entry and at the completion of treatment. Labial minor salivary gland tissue was obtained at these times and examined for intensity of infiltration (focus scores) and for the relative proportion of glandular elements. Serologic and subjective evaluations were done as well, and patients were monitored for therapy-related side effects. Neither active treatment led to significant improvement in salivary or lacrimal function, although prednisone improved salivary flow in selected patients and was associated with positive subjective responses. Prednisone also significantly decreased the serum total protein, IgG, IgA, and sedimentation rate and increased the white cell count. There were no significant alterations in either focus scores or the percentage of glandular component tissues of minor glands with either active treatment. This study demonstrated that 6 months of prednisone or piroxicam at the doses utilized failed to improve the histological or functional parameters of salivary and lacrimal glands in primary Sjogren's syndrome. PMID- 8508557 TI - Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. AB - Sex hormones have profound effects on immune responses and may influence the outcome of autoimmune diseases such as rheumatoid arthritis (RA). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL 6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy male donors and male patients with RA, and were stimulated with lipopolysaccharide (LPS) in the presence of different concentrations of 17-beta-estradiol, progesterone or testosterone. In studies of cells from normal male donors, 17-beta-estradiol at pharmacological concentrations (> or = 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibited IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and progesterone failed to inhibit IL-1 secretion. The inhibitory effects of testosterone, however, appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 production and release, while gestation hormone, progesterone, and testosterone may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low and androgen levels. PMID- 8508558 TI - Sensitivity of magnetic resonance imaging of the wrist in very early rheumatoid arthritis. AB - The aim of this study was to evaluate magnetic resonance images (MRI) of soft tissue abnormalities in the wrist of RA patients in the early stage of the disease. We performed magnetic resonance imaging of the wrist in 15 patients with early rheumatoid arthritis according to ACR criteria, of less than 10 months duration (mean duration 4.8 months). None of the patients had carpal bone erosions on standard radiography. MRI demonstrated abnormality of the soft tissue in 13 of the 15 cases. On coronal MRI, the sites of involvement of the synovitis were the recess of the distal ulnar (9 pts.), the distal radioulnar joint (4 pts.) and the radiocarpal joint (7 pts.). On axial MRI, tendon sheath effusion of the digital flexor was present in 3 patients. Carpal bone lacunae were present in only 4 patients. Disease activity was not associated with the extent of the synovitis on wrist MRI. Our study suggests that MRI is a sensitive method for the detection of synovitis in early RA. PMID- 8508559 TI - The onset of rheumatoid arthritis in relation to pregnancy and childbirth. AB - It has been suggested that the onset of RA symptoms is reduced during pregnancy and increased in the postpartum period. In the present study symptom onset in relation to the pregnancy prior to disease onset was compared between 135 young RA patients with definite RA and 378 controls with soft tissue rheumatism or osteoarthritis. Two RA patients developed symptoms during pregnancy versus 9 controls (odds ratio OR = 0.64). In the 3 months postpartum 5 RA patients and 5 controls developed symptoms (OR = 3.37). These results show the same trend as those of previous studies, i.e. a decrease in the onset of RA during pregnancy and an increased onset of RA after delivery. These findings might be explained by a delayed clinical onset of RA that started during pregnancy, analogous with the ameliorating effect of pregnancy on the course of existing RA and the flare-up of disease activity in the postpartum period. PMID- 8508560 TI - Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82). AB - A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects. PMID- 8508561 TI - A case of Adamantiadis-Behcet's syndrome presenting as myocardial infarction. AB - We report a case of a 27-year-old man who presented with an acute myocardial infarction. When he was hospitalized one month later to evaluate this recent event, he developed clinical findings consistent with the diagnosis of Adamantiadis-Behcet's syndrome. We believe that the myocardial infarction was due to coronary arteritis, because there were no risk factors for coronary disease present. PMID- 8508562 TI - HIV infection and Salmonella septic arthritis. AB - Human immunodeficiency virus (HIV) infection predisposes to bacterial infection at may sites but septic arthritis is notably uncommon. An HIV seropositive patient who presented with oligoarticular septic arthritis due to Salmonella enteritidis and who responded poorly to antibiotic therapy and repeated aspiration of involved joints is described. Unusual features included the clinical presentation of septic arthritis in more than one joint, a protracted clinical course with radiological destruction of the hip, bone marrow suppression induced by cotrimoxazole, and death thought to be due to a gastropathy induced by non-steroidal anti-inflammatory therapy at a time when the septic arthritis appeared to have responded to treatment. Cure of Salmonella septic arthritis in HIV infected patients may be difficult and require aggressive prolonged treatment. Septic arthritis should be considered in the differential diagnosis in a patient with HIV infection and arthritis. PMID- 8508563 TI - Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis. PMID- 8508564 TI - Cyclosporin A in the treatment of juvenile chronic arthritis and childhood polymyositis-dermatomyositis. Results of a preliminary study. AB - In this study we have investigated the efficacy and safety of cyclosporin A (CyA) in a group of pediatric patients with juvenile chronic arthritis (JCA, 9 cases) and polymyositis-dermatomyositis (PM-DM, 3 cases). Of the 9 JCA patients, 7 had the systemic and 2 the polyarticular form of the disease. All of the patients received CyA after the failure of corticosteroids and/or cytotoxic drugs. CyA was administered for 9 to 48 months at a mean dose of 5 mg/kg/day. Ten patients received corticosteroids with CyA. The results of CyA treatment were satisfactory overall, both in the PM-DM patients and in the JCA patients, as assessed by clinical and laboratory evaluation. CyA-related side effects included alopecia, hypertension, hypertrichosis, tremors, and hirsutism. One JCA patient developed polyserositis with hypoproteinemia of unknown origin while receiving CyA. CyA blood levels did not correlate with clinical efficacy and/or side effects. This study suggests that CyA represents a promising agent for the treatment of JCA and childhood PM-DM. PMID- 8508565 TI - A new case of reactive arthritis after hepatitis B vaccination. PMID- 8508566 TI - Identification of calcium pyrophosphate dihydrate crystals. PMID- 8508567 TI - Idiopathic thrombocytopenic purpura and monoclonal gammopathy of undetermined significance accompanied by urinary bladder carcinoma. PMID- 8508568 TI - Second International Workshop on Reactive Arthritis. PMID- 8508569 TI - Tc-99m labeled monoclonal antibodies against granulocytes (BW 250/183) in the detection of appendicitis. AB - Scintigraphy with Tc-99m labeled antigranulocyte antibodies (BW 250/183 MoABs) was performed in 32 patients with suspected appendicitis. Abdominal imaging (planar/SPECT) was performed 2 hours after injection of the tracer. All patients also had surgery and a histologic examination of the resected tissue. Of the patients, 17 suffered from "acute appendicitis" and 12 had right positive scans (sensitivity = 70.6%). In 15 patients, acute appendicitis could have been ruled out, and in 11 of these cases the scan was true negative (specificity = 73.3%). The overall accuracy was 71.8% (23/32 cases). The use of Tc-99m antigranulocyte MoABs may overcome the problems associated with the Tc-99m HMPAO granulocyte and In-111 oxine approaches, which include nonspecific intestinal activity or the lack of timeliness. The use of Tc-99m labeled antigranulocyte antibodies is suitable as an emergency procedure and may play a role in the management of patients with suspected appendicitis. PMID- 8508570 TI - A pitfall in calculating differential renal function in patients with renal failure. AB - Measurement of relative renal function in azotemic patients can be misleading due to elevated background activity and delayed renal concentration of radiotracer. When there is delayed excretion of the tracer and obvious splenic or hepatic activity superimposed over one of the kidneys, it often is advantageous to delay the differential uptake measurement to allow renal activity to increase and background activity to decrease rather than use the standard 1- to 2- or 2- to 3 minute interval after radiopharmaceutical injection. The accompanying case illustrates the use of delayed images to obtain a more accurate assessment of relative renal function. The measurement must be made before the excretion of tracer into the ureter or bladder. PMID- 8508571 TI - The additional value of visual findings in captopril-enhanced renal scintigraphy with Tc-99m MAG3. AB - Captopril-enhanced renal scintigraphy has become an important tool in the diagnosis of renovascular hypertension. The evaluation of these studies typically is based on a quantitative analysis of changes in renal radiotracer handling after angiotensin-converting enzyme inhibition. The use of mercaptoacetyltriglycine (MAG3) in these studies offers the optimum photon energy and high photon yield of a Tc-99m label with efficient renal extraction of tracer by tubular secretion. These qualities of Tc-99m MAG3 combine to produce high resolution scintigraphic images that may supply additional valuable diagnostic information by visual assessment of the scintigraphic data. A series of cases illustrating the value of these visual findings is presented. PMID- 8508572 TI - Phase II study of Tc-99m MAG3 in patients with nephrourologic diseases. AB - Tc-99m-labeled mercaptoacetyltriglycine (Tc-99m MAG3) is a recently introduced radioagent that is excreted by tubular function. The aim of this study was to test Tc-99m MAG3 as an imaging agent for renal scintigraphy and renal plasma flow measurement. Image quality was tested with four different administered doses of Tc-99m MAG3, 100 MBq, 200 MBq, 300 MBq and 400 MBq, in four patients each. All administered doses except 100 MBq were sufficient for visible inspection of the nephrogram and drainage images; however, an administered dose higher than 300 MBq was necessary to maintain the quality of the blood perfusion image. The blood clearance with Tc-99m MAG3 or I-131 orthoiodohippurate (I-131 OIH) was calculated within the same day by the single blood sampling method. The blood clearance with Tc-99m MAG3 was 1.2-fold lower than with I-131 OIH, but correlated well (OIH = 91.34 +/- 0.932 MAG3, r = 0.953, P < 0.001). The blood clearance with Tc-99m MAG3 also correlated with the percentage of renal uptake estimated by the count-based gamma camera method at 1.5 to 2.5 minutes after injection (ERPF = -59.13% +/- 16.87% uptake, r = 0.845, P < 0.01). The mean labeling yield of Tc-99m MAG3 was 97%. None of the patients complained of side effects from Tc-99m MAG3. Tc-99m MAG3 is concluded to have good properties as a tubular radioagent for dynamic renal scintigraphy and renal plasma flow measurement. PMID- 8508573 TI - The determination of dual pancreatic and renal transplant graft vascular patency with Tc-99m HMPAO. AB - Combined pancreatic-renal transplants promise the restoration of physiologic control of serum glucose and normal renal function. As pancreatic transplantation becomes more common, there is an increased need for rapid, noninvasive evaluation of vascular graft patency and function. Pancreatic transplants share the renal transplant's complications of ischemia at harvest but are at greater risk. Tc-99m HMPAO is a lipophilic complex that clears rapidly from the blood after intravenous injection, and tissue accumulation is proportional to regional perfusion. Using Tc-99m HMPAO to monitor the vascular competency has the advantage of a high count rate during dynamic scintigrams but, in contrast to Tc 99m DTPA, has excellent delayed static images. Four patients who received combined cadaveric pancreatic-renal transplants and had a total of eight Tc-99m HMPAO scintigraphic examinations were reviewed. PMID- 8508574 TI - Scintigraphic recognition of papillary muscles and papillary muscle ischemia. AB - During stress thallium imaging, papillary muscles (anterolateral and posteromedial) appear scintigraphically as focal regions of enhanced activity in sites corresponding to their anatomic position. In the normal case, enhancement after exercise is greater than or equal to enhancement at rest. With papillary muscle ischemia, the involved papillary muscle demonstrates more enhanced activity at rest than at postexercise. This pattern change with papillary muscle ischemia was observed in four patients. Three cases demonstrated complete reversal of those ischemic changes after angioplasty and the remaining case failed to show any significant improvement after angioplasty. PMID- 8508575 TI - Demonstration of focal brain ischemia induced by hyperventilation using Tc-99m HMPAO SPECT. AB - A case with vasospasm of the right anterior cerebral artery induced by hyperventilation is presented. Consecutive Tc-99m HMPAO brain SPECT studies at rest and during hyperventilation greatly contributed to the quantitative evaluation of focal perfusion decrease in conjunction with contrast angiography. This technique seems to be useful for the detection of alterations in regional brain perfusion during short duration intervention. PMID- 8508576 TI - Hyperemic receptive aphasia on neuroSPECT. AB - NeuroSPECT of regional cerebral blood flow (rCBF) with Tc-99m HMPAO demonstrated left temporoparietal hyperemia in two patients with acute receptive aphasia. This finding prompted further testing with electroencephalography that added to the impression of ictal dysphasia. The differential diagnosis in one case included complicated migraine. NeuroSPECT depicts blood flow abnormalities in acute aphasic disorders, either due to ischemia, which is most commonly the cause, or due to hyperemia secondary to migraine or epilepsy. The treatment and prognosis of these latter conditions differ from stroke, and thus SPECT plays a role in patient management. PMID- 8508577 TI - Brain SPECT in a patient with post-stroke hallucination. AB - A patient developed visual hallucinations following a left-sided cerebrovascular accident (CVA). Brain SPECT using Tc-99m HMPAO demonstrated increased perfusion at the biparieto-occipital lobes. Following antiepileptic medication, repeat brain SPECT showed interval decrease in perfusion in the same areas with the symptomatic relief of hallucinatory episode. While it is possible that the interval decrease is due to natural resolution, the authors believe that it is likely due to drug treatment. PMID- 8508578 TI - Radionuclide hepatobiliary scanning in patients with AIDS-related sclerosing cholangitis. AB - Biliary disease, primarily manifesting as papillary stenosis or sclerosing cholangitis, is being increasingly recognized as a problem in the acquired immunodeficiency syndrome (AIDS) and may be amenable to specific treatment. Ultrasound, followed by endoscopic retrograde cholangiopancreatography (ERCP) for definitive diagnosis, is currently the prime mode of investigation of suspected hepatobiliary diseases in AIDS. There are few published reports of the use of radionuclide cholescintigraphy in the assessment of these patients. This report presents Tc-99m DISIDA cholescintigraphy data from three patients with AIDS related hepatobiliary disease confirmed by ERCP. Radionuclide cholescintigraphy was abnormal in all three patients. In two of the subjects, there was focal duct dilation with strictures in the biliary tree. The third patient demonstrated diffuse hepatic parenchymal retention with marked delay in tracer washout. Two of the subjects, treated with specific anticryptosporidial therapy, subsequently underwent progress cholescintigraphy. In one of these patients with initial diffuse parenchymal retention, there was marked improvement in scan appearances. The second patient with initial duct dilation had no significant change in scan appearances, but quantitative analysis did demonstrate improvement in hepatobiliary tracer clearance rate. In conclusion, although ERCP remains the gold standard in the diagnosis of AIDS-related biliary disease, radionuclide cholescintigraphy may be a useful modality in these patients as a screening test before proceeding to more expensive and invasive techniques. In addition, quantitative analysis of cholescintigraphy may allow assessment of patient response to specific antimicrobial or surgical intervention. PMID- 8508579 TI - Scintigraphic evaluation of reduced-size liver transplant from living related donor in Byler's disease. AB - Byler's syndrome is a rare form of autosomal recessive intrahepatic cholestasis that is fatal in children. A 10-year-old girl diagnosed with Byler's syndrome underwent reduced-size liver transplantation using lateral segments of her living mother's liver. The donor's and the recipient's liver functions after transplantation were evaluated using Tc-99m disofenin and Tc-99m SC to investigate morphology, liver perfusion, and hepatobiliary function. PMID- 8508580 TI - A rare case of sebaceous carcinoma with very malignant characteristics. AB - A case of a sebaceous carcinoma is presented. This carcinoma of the skin appendages requires diagnosis by histopathology because the clinical appearance is often atypical. Because of the frequency of metastases to local lymph nodes and bone, a careful physical examination and appropriate radiologic/scintigraphic examinations of these organs should be performed routinely. The case presented illustrates the very malignant character of this tumor. PMID- 8508581 TI - The diagnosis of brain death with Tc-99m HMPAO. AB - Evaluation of blood flow to the brain using various radiopharmaceuticals can be used to confirm brain death. Agents available for this purpose include Tc-99m HMPAO, Tc-99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m DTPA. The authors evaluated the use of Tc-99m HMPAO in 17 patients suspected of brain death using flow images and static images at several time intervals: immediately, between 30 and 60 minutes, and at 2 hours. These studies were compared to several studies performed with Tc-99m glucoheptonate and Tc-99m DTPA. The results of the Tc-99m HMPAO brain death studies correlated well with the patients' clinical conditions. Static images 1 to 2 hours after the injection of 5 to 30 mCi of Tc-99m HMPAO were satisfactory for an accurate interpretation; however, an immediate answer could as easily be supplied using flow images alone. Tc-99m HMPAO was found to be more easily interpreted and less dependent on imaging technique than Tc-99m glucoheptonate and Tc-99m DTPA, and it is the agent of choice for the evaluation of brain death. PMID- 8508582 TI - Uriposia after intravenous administration of technetium-99m HMDP. PMID- 8508583 TI - Cerebrospinal fluid leak from epidural spinal anesthesia detected by radionuclide cisternogram. PMID- 8508585 TI - Detection of recurrent renal cell carcinoma by three-phase bone scan. PMID- 8508584 TI - Skeletal photopenic lesions on indium-111 WBC imaging; differential diagnosis. PMID- 8508586 TI - Minimal plain film findings of a femoral neck osteoid osteoma diagnosed by radionuclide bone scintigraphy and MRI. PMID- 8508587 TI - Incidental detection of bronchogenic carcinoma during Tc-99m SESTAMIBI cardiac imaging. PMID- 8508588 TI - Potential false-positive bone scan secondary to a calcified venous thrombus. PMID- 8508589 TI - Changes of Tc-99m HMPAO brain distribution in herpes encephalitis. PMID- 8508590 TI - Detection of soft tissue hemangioma of the leg by Tc-99m DTPA-HSA blood pool imaging. PMID- 8508591 TI - Magnetic resonance imaging with Gadolinium-DTPA for assessment of bladder carcinoma and its response to treatment. AB - Magnetic Resonance Imaging (MRI) with intravenous Gadolinium-DTPA (Gd-DTPA, Magnevist, Schering-AG) was performed in 44 patients, 32 with primary bladder carcinoma and 12 with suspected recurrence after treatment. Gd-DTPA often increased diagnostic confidence in the identification and staging of tumours confined to the bladder wall and was necessary to assess depth of bladder wall invasion when T2-weighted images were suboptimal. Enhancement after Gd-DTPA enabled distinction between necrotic and viable tumour and blood clot. There was little advantage in its use for tumours infiltrating perivesical fat or with metastases to lymph nodes or bone, in the absence of a fat suppression sequence. Gd-DTPA may therefore be useful in selected patients with tumours of Stage T3a or less in whom information about depth of bladder wall invasion is inadequately shown on pre-contrast sequences. Artefacts due to variable and inhomogeneous urine signal intensity, however, often degraded post-Gd-DTPA images of the bladder. Changes in the bladder due to radiotherapy were observed on MRI 3-4 months after treatment in patients referred for routine follow-up and in some patients with suspected recurrence. Mucosal hyperintensity, thickening and abnormal signal intensity of the muscular layers of the bladder wall, with enhancement after Gd-DTPA were demonstrated. Such changes obscured small volume or superficial recurrence of tumour after radiotherapy. Abnormal enhancement was also observed in pelvic organs and soft tissues irradiated several years earlier. Enhancement after Gd-DTPA does not therefore reliably distinguish between recurrent tumour and radiotherapy change. PMID- 8508592 TI - MRI: early onset of changes in Wallerian degeneration. AB - T2-weighted spin echo scans were performed on a neonate and two adults aged 42 and 60 years within 2 weeks of the onset of infarction in the frontoparietal region of the brain. Areas of increased signal intensity were observed in the anterior and posterior limbs of the internal capsule in the infant and in the posterior limbs of the internal capsules in the adults. Although these signal changes were typical of the chronic phase of Wallerian degeneration, their onset was much earlier than the 10-14 weeks previously described for this stage in adults. The low level of myelination of white matter tracts at birth, and the relatively sparse myelination of the parietopontine tract may account for the rapid onset of changes in these patients which more closely follows the time course described pathologically for Wallerian degeneration in unmyelinated fibres. PMID- 8508594 TI - Intrahepatic biliary stones: imaging features and a possible relationship with ascaris lumbricoides. AB - Intrahepatic (IH) biliary stones are common in East Asia as part of a disease known as Oriental cholangiohepatitis (OCH). At a hospital serving non-Oriental communities, 40 patients were diagnosed on ultrasound (US) during an 8-year period as having IH stones. Follow-up showed that the diagnosis was false in three cases. In the 37 patients with IH stones, 33 conventional retrograde cholangiograms were done; 26 underestimated the IH abnormalities or missed them entirely. Computed tomography (CT) was done in 15 of these 37 patients; the attenuation of the stones was found to be only slightly above that of liver. The evidence that Ascaris lumbricoides was the cause of IH stones in our patients was that: they came mainly from communities in which A. lumbricoides infestation is virtually universal at some stage of childhood, and none from communities in which it is infrequent; their average age was younger than that of patients with conventional gall-stones, fitting with the fact that infestation is predominantly in childhood; A. lumbricoides is the only parasite in our region that invades the biliary system; the histories of the first 12 of the 37 patients had been investigated for intestinal infestation, and were all positive; and 12 of the 37 showed evidence at some time of roundworms or remnants in the biliary system, either within the US appearance of the stones ('bundles' and 'pipes') or separately on US, surgery or duodenoscopy. Biliary strictures, which occur in OCH, were not seen in our patients. PMID- 8508593 TI - Hepatic arterial haemodynamics changes following intra-arterial angiotensin II infusion: duplex/colour Doppler sonography. AB - Previous studies have shown that the delivery of cytotoxic microspheres to liver tumours may be improved by manipulating the tumour to normal liver blood flow ratio using angiotensin II (AT-II). The optimization of this targeting requires the assessment of the temporal blood flow changes induced by agents such as AT II. Duplex/colour Doppler sonography (DCDS) was evaluated as a means of studying the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with colorectal liver metastases. HABF was measured continuously in six patients with colorectal liver metastases using DCDS before, during and after an infusion of AT-II (15 micrograms in 3 ml of saline over 90 s) via a hepatic artery catheter. The baseline level of HABF was 320 +/- 87 ml/min (mean +/- S.D.), and this was reduced by 70-76% within 30 s of the start of AT-II infusion. HABF recovered rapidly from the end of the infusion, and increased by up to 20% above the baseline for approximately 2 min. Arterial resistance showed reciprocal changes in all cases. These changes were both quantitatively and qualitatively similar to intra-operative measurements previously performed in the same patients using a standard intra-operative flowmeter. The degree of concordance obtained from the intra- and post-operative measurements confirms the effectiveness of DCDS in assessing the temporal changes in hepatic arterial blood flow caused by AT-II. Prior to the start of therapy, the evaluation of vasoconstrictor agents should be carried out in individual patients to predict response, in order to establish the optimal phase for the injection of cytotoxic microspheres. PMID- 8508595 TI - Ultrasonography and plain film versus intravenous urography in ureteric colic. AB - Urography (IVU) is considered the best first investigation in patients with suspected ureteric colic, but recently ultrasonography (US), combined with a plain film of the abdomen (KUB), has been suggested as an alternative. We have undertaken a prospective study to see if this approach can be used in an Emergency Department by radiologists with different amounts of ultrasound experience. Some 180 patients with suspected ureteric colic presenting to the Emergency Department over an 8-month period were studied. They had a plain abdominal film (KUB) and US examination of the kidneys, ureters and bladder following hydration. Some 120 patients subsequently underwent IVU at a mean interval of 3.5 days after the ultrasound examination. Of these, 15 patients passed a stone before their IVU. Of the remaining 105 patients, 44 had an IVU positive for stone and 61 had a negative IVU. Fifty of the 60 patients who did not have an IVU had clinical follow-up and 31 had ultrasound. Our findings in this prospective study suggest that in the hydrated patient the combination of KUB plus US is a sensitive but not very specific screening test (sensitivity 95%, specificity 67%). Because of the high negative predictive value of KUB plus US (95%), urography is not likely to be helpful when KUB plus US are negative. Urography is indicated only if KUB plus US findings are equivocal or if intervention is necessary. If we had used KUB plus US alone as the first test in our patients, urography would have been unnecessary in approximately 60%. Twenty per cent of our patients passed a stone in the first 48 h. PMID- 8508596 TI - Non-invasive ultrasound localization of impalpable breast lesions. AB - Thirty patients presenting through the Breast Screening Programme with impalpable breast abnormalities clearly visible on ultrasound, underwent non-invasive ultrasound localization. The patient was scanned so that the ultrasound abnormality lay below the probe and the skin at this site marked with a skin marker. In all cases the abnormality was easily identified and removed at surgery. All the surgical biopsies contained either a carcinoma (17 cases) or fibroadenoma (13 cases). This non-invasive technique is a simple and accurate method for localizing small ultrasonically visible breast abnormalities. PMID- 8508597 TI - Mammography in the assessment of response to medical treatment of large primary breast cancer. AB - The sequential mammograms of 48 patients (median age: 54 years, range: 24-84 years) undergoing primary medical treatment for large operable breast cancer at this institution were reviewed, and compared to the findings at clinical assessment. Twenty-six patients underwent endocrine therapy using tamoxifen, and 22 chemotherapy (CMF or MMM). All had more than two mammograms which were reviewed blindly by two independent radiologists. Response to treatment by both evaluation modalities was recorded using WHO definitions (NC, PR, CR, PD). Some 81% of patients achieved an objective clinical response to treatment, whilst 63% showed mammographic response. Overall comparison of clinical examination with mammography showed agreement in 38 patients (79%) and disagreement in 10 (21%). Agreement in type of response but not in its degree was found in 22 cases (46%). The results suggest that in the majority of cases mammography provides a useful adjunct to clinical examination in monitoring response to primary medical treatment for breast cancer. However, radiological factors such as unchanging microcalcification, and the continuing presence of mammographic density contribute to the discrepancy with clinical response in some tumours, and the search for alternative modalities of assessment should continue. PMID- 8508598 TI - Hypophosphataemic rickets after ifosfamide treatment in children. AB - Ifosfamide is a derivative of cyclophosphamide and is used to treat malignant tumours. One of its side effects is nephrotoxicity. Three children with previously normal renal function, who received ifosfamide for the treatment of Ewing's Sarcoma and subsequently developed hypophosphataemic rickets, are described. PMID- 8508599 TI - Intraosseous lipomas. AB - Intraosseous lipomas are considered to be rare tumours. We describe four cases and discuss their appearances and diagnosis. It is likely with the increasing frequency of computed tomography and magnetic resonance examinations of the lumbar spine that many more asymptomatic lesions will present to the radiologist and that these tumours are not as rare as the literature would suggest. PMID- 8508600 TI - Utility of the instant (unprepared) enema in Crohn's colitis. AB - Thirty-seven instant (unprepared) barium enemas in 30 patients with proven Crohn's colitis were reviewed. Plain films in 28 indicated that confluence or discontinuity of the colitis did not substantially alter the pattern of faecal residue. In only one patient was residue found overlying active mucosal disease. Aphthoid ulceration was demonstrated in 27%. In five (13%) examinations the colitis was granular and indistinguishable from ulcerative colitis. In 26/37 (70%) typical stigmata of Crohn's colitis were present. There was no complication or clinical deterioration after the instant enema. The instant enema was found to be comparable to a prepared examination for the diagnosis of advanced Crohn's disease, though less accurate for demonstrating early changes. PMID- 8508601 TI - Case report: wandering intravascular bullet with aortic pseudoaneurysm. AB - A 26-year-old man received a gunshot wound to the left flank. No exit wound was seen. A plain abdominal film, computed tomography (CT) and angiography were performed. Abdominal aortic pseudoaneurysm with extravasation of contrast into the retroperitoneum and embolization of the bullet to the left iliac artery were shown. The diagnostic value of the CT was considerable, but angiography was still required for definitive localization of the bullet. PMID- 8508602 TI - Case report: thrombosis of the inferior vena cava--an unusual presentation of protein C deficiency. AB - In children, venous thrombosis is uncommon and this is true particularly for one of the inferior vena cava. Recurrent superficial venous thrombosis is a well recognized presenting symptom of Protein C deficiency but thrombosis of the inferior vena cava as the initial manifestation of this condition has only rarely been reported. We present a case of a 13-year-old boy in whom the first indication of Protein C deficiency was an isolated thrombosis in the intra hepatic inferior vena cava noted on a routine ultrasound examination. PMID- 8508603 TI - Case report: thyrocervical arterial supply to an intracranial dural arteriovenous malformation. AB - An intracranial dural arteriovenous malformation (DAVM) is presented, which received some of its blood supply from the left thyrocervical trunk. Since arterial supply from the thyrocervical trunk is not revealed by routine four vessel cerebral angiography, opacification of the ipsilateral thyrocervical trunk is advocated in patients with posterior fossa DAVMs for whom endovascular treatment is being considered. PMID- 8508604 TI - Case report: direct cellulitic spread as presentation of a liver abscess- ultrasound, CT and contrast imaging. AB - A case of a pyogenic liver abscess presenting as cellulitis of the anterior abdominal wall in a patient with myelodysplasia is reported. Ultrasound (US) and computed tomography (CT) images are compared and the follow-up and treatment is discussed. PMID- 8508605 TI - Intravenous urography: injection of contrast agents by radiographers. PMID- 8508606 TI - Percutaneous biliary drainage without lateral fluoroscopy. PMID- 8508607 TI - Percutaneous biliary drainage without lateral fluoroscopy. PMID- 8508608 TI - Therapeutic renal embolization. PMID- 8508609 TI - Prevertebral swelling in cervical spine injury: identification of ligament injury with magnetic resonance imaging. PMID- 8508610 TI - Databases and diabetes: dogsbodies or devils? PMID- 8508611 TI - Insulin deficiency rather than hyperinsulinaemia in newly diagnosed type 2 diabetes mellitus. AB - This paper reports beta cell function as assessed during OGTT using specific IRMAs for insulin, intact and 32/33 split proinsulin in subjects with newly diagnosed Type 2 diabetes matched to normal controls. The relationships between insulin and the proinsulins to risk factors for cardiovascular disease were also examined. Similar fasting insulin concentrations but lower 30-min post-glucose load insulin concentrations were found in diabetic subjects (mean +/- SEM 143 +/- 12 pmol-1 vs 304 +/- 19 (p < 0.001). Subjects with diabetes had increased fasting intact (10.6 +/- 1.1 pmol-1 vs 3.3 +/- 0.2, p < 0.001) and 32/33 split proinsulin concentrations (8.1 +/- 0.9 pmol-1 vs 2.2 +/- 0.3, p < 0.0001). Beta cell dysfunction, as expressed by a reduction in the 30-min insulin to glucose ratio (9.4 +/- 1 vs 34.8 +/- 2.3, p < 0.0001) and an increase in the fasting percentage of total proinsulin-like to total insulin-like molecules (24.5 +/- 9% vs 11.6 +/- 5, p < 0.001), was present in subjects with diabetes. In diabetic subjects beta cell dysfunction and insulin deficiency increased relative to the degree of fasting hyperglycaemia. It seems clear that beta cell dysfunction and insulin deficiency are major features of Type 2 diabetes. Only the fasting concentration of 32/33 split proinsulin positively correlated with both the waist/hip ratio (r = 0.36, p < 0.001), diastolic blood pressure (r = 0.23, p < 0.01) in addition to plasma triglyceride concentration (r = 0.46, p < 0.001). It is questionable whether hyperinsulinaemia plays a pathogenic role in cardiovascular disease in subjects with glucose intolerance. PMID- 8508612 TI - Insulin deficiency and increased plasma concentration of intact and 32/33 split proinsulin in subjects with impaired glucose tolerance. AB - In order to determine insulin status and beta cell function during the oral glucose tolerance test (OGTT), in impaired glucose tolerance (IGT), 51 such subjects and matched controls, identified during a population survey for diabetes, underwent a 75 g OGTT. Fasting, 30 min and 2 h insulin and intact proinsulin, and fasting and 2 h 32/33 split proinsulin, were measured by specific two-site immunoradiometric assays. The subjects with IGT had higher fasting (geometric mean +/- SD, 5.0 +/- 4.0 pmol-1 vs 2.9 +/- 1.7, p < 0.02) and 2 h intact proinsulin (23 +/- 14 vs 14 +/- 12, p < 0.0001), and fasting (3.2 +/- 3 pmol-1 vs 1.8 +/- 1.8, p < 0.0007) and 2 h 32/33 split proinsulin (18.3 +/- 19 pmol-1 vs 6.6 +/- 15, p < 0.0001). Despite higher plasma glucose concentrations, the IGT group had similar fasting insulin, lower 30 min insulin (216 +/- 124 pmol 1 vs 278 +/- 130, p < 0.02), and a lower 30 min insulin/glucose ratio (23.7 +/- 2.1 vs 34.8 +/- 2.3, p < 0.002). The percentage of fasting proinsulin-like to total insulin-like molecules was higher in those with IGT (15.3 +/- 8% vs 11.6 +/ 8, p < 0.04). After 6 months, at repeat OGTT, the same subjects with IGT were classified as 'persisters' or 'reverters'. The persister (24/51 47.1%), at initial OGTT, had a higher 2 h glucose level, a greater BMI and higher systolic blood pressure, but other parameters were similar to the reverters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508613 TI - Hyperglycaemic progression in subjects with impaired glucose tolerance: association with decline in beta cell function. AB - Impaired glucose tolerance is associated with an increased risk of Type 2 diabetes. This prospective cohort study has examined the variables associated with hyperglycaemic progression in order to elucidate the aetiology of this deterioration. The 5 mg glucose.kg ideal body weight.min-1 continuous infusion of glucose with model assessment (CIGMA) test was used to quantitate glucose tolerance, beta cell function, and insulin sensitivity. Twenty-two Caucasian subjects who had impaired glucose tolerance identified on two separate tests underwent repeat testing after a median period of 24 months. At follow-up, 2 of the 22 subjects (9%) had Type 2 diabetes, 18 (82%) had impaired glucose tolerance, and 2 (9%) were normoglycaemic. The fasting and achieved (60-min) glucose levels were significantly higher at follow-up (mean +/- SD) (5.7 +/- 0.8 vs 5.5 +/- 0.5 mmol l-1, p = 0.029 and 10.0 +/- 0.9 vs 9.6 +/- 0.6 mmol l-1, p = 0.021, respectively), and beta cell function was significantly lower (median and interquartile range): 75% (50-93%) vs 90% (70-135%), p = 0.009. The changes in fasting plasma glucose were found to correlate with change in body mass index (rs = 0.46, p = 0.03). We conclude that impaired glucose tolerance is associated with decline in beta cell function, and denotes substantial risk of hyperglycaemic progression. Randomized controlled trials are warranted to determine whether exercise programmes, dietary advice, and attentive follow-up and effective preventive strategies for subjects with impaired glucose tolerance. PMID- 8508614 TI - Plasma concentrations of islet amyloid polypeptide after glucagon administration in type 2 diabetic patients and non-diabetic subjects. AB - Islet amyloid polypeptide (IAPP) is the main constituent of pancreatic islet amyloid, observed in the pancreases from patients with Type 2 diabetes mellitus. IAPP is synthesized by the pancreatic beta-cells. In order to study the secretion characteristics of IAPP in Type 2 diabetes mellitus, plasma IAPP was measured during a provocation test with glucagon in 33 Type 2 diabetic patients and 18 non diabetic subjects. The median fasting IAPP level was 5.7 (range 1.1-13.1) pmol l 1 in the 27 patients treated with oral hypoglycaemic agents and 2.7 (1.9-5.9) in the 6 patients on insulin. In the non-diabetic group fasting IAPP was 5.7 (2.2 10.1). Six minutes after glucagon administration median IAPP rose to 9.4 (1.7 31.0) and 6.1 (5.1-10.2) in the respective diabetic groups, and to 16.8 (4.0 41.0) in the non-diabetic subjects (p << 0.05). The correlation coefficient between change in IAPP and change in C-peptide was 0.68 in the diabetic group. We conclude that intravenous administration of glucagon stimulates IAPP release from the beta-cell. This provocation test is easy to perform and can be used on a large scale in the study of IAPP secretion in Type 2 diabetes mellitus. PMID- 8508615 TI - A comparison of different methods of assessing free radical activity in type 2 diabetes and peripheral vascular disease. AB - Increased free radical activity in diabetes mellitus may contribute to the higher prevalence and mortality from macrovascular disease in diabetic patients. To investigate this, levels of plasma antioxidants (superoxide dismutase, caeruloplasmin, plasma, and lysate thiol), diene conjugates, lipid peroxides, and chemiluminescence were measured in diabetic and non-diabetic patients with peripheral vascular disease compared with healthy control subjects. Caeruloplasmin, diene conjugate ratio, and lipid peroxides were significantly increased in patients with vascular disease but there was no difference between diabetic and non-diabetic patients. Conjugated diene ratio correlated with caeruloplasmin (r = 0.40, p < 0.02) and inversely with superoxide dismutase level (r = 0.36, p < 0.05) but there was no significant correlation between other antioxidants and diene conjugates, lipid peroxides or chemiluminescence. The relationship between different indirect measurements of free radical activity is variable but there appears to be no additive effect of diabetes on the increased free radical activity associated with vascular disease. PMID- 8508616 TI - Thrombin generation and factor VIII:C levels in patients with type 1 diabetes complicated by nephropathy. AB - The association between plasma coagulant activity and the presence of diabetic nephropathy was investigated in 31 patients with Type 1 diabetes, 12 with and 19 without nephropathy, and in 11 healthy subjects. Thrombin generation was assessed by computer assisted chromogenic method and expressed as time (in seconds) to 50% maximal thrombin activity (T50). Factor VIII:C levels related to thrombin activity, glycaemic control, and renal function. Median (IQ) FVIII:C concentration was increased in patients with nephropathy (1590 (1130-1900) IU l 1) compared to those without renal disease and with controls (960 (750-1090); 1020 (810-1100) IU l-1, p < 0.01, respectively). There were no significant differences in T50 values between the groups. FVIII:C correlated with age in all subjects and in the diabetic group (r = 0.33, p = 0.036; r = 0.39, p = 0.031) and inversely with T50 in all subjects and in controls (r = -0.35, p = 0.02; r = 0.62, p = 0.04). In all subjects and in patients, FVIII:C was related to urinary albumin excretion and creatinine clearance. FVIII:C and T50 were not related to HbA1c. The results show that FVIII:C levels are increased in Type 1 diabetes complicated by nephropathy and are related to degree of renal impairment but not levels of glycaemia. No associated enhancement of plasma procoagulant activity was detected. PMID- 8508617 TI - Calcium metabolism in diabetes mellitus: effect of improved blood glucose control. AB - Reduced bone mass occurring with increased frequency in diabetes mellitus has been attributed to poor blood glucose control but the pathogenetic mechanisms remain unknown. To evaluate the role of calcium metabolism, 59 patients with diabetes and normal renal function (22 Type 1, 37 Type 2) were studied. In all patients plasma calcium (Ca), serum phosphate (PO4), serum parathyroid hormone (PTH), and 24-h urinary calcium (uCa) were determined under both poor and improved control (for at least 7 days) as ascertained by four blood glucose determinations daily. Improvement of blood glucose control (p = 0.001) was associated with reduction of uCa both in Type 1 (6.9 +/- 1 vs 4.9 +/- 0.9 mmol day-1, mean +/- SEM, p = 0.02) and in Type 2 patients (4.2 +/- 0.4 vs 3.2 +/- 0.4 mmol day-1, mean +/- SEM, p = 0.002). Considerably more Type 1 patients (10 out of 22) had PTH values below the detection limit (1.5 pmol l-1) during poor than during improved control (2 out of 22). Comparison between the two types of diabetes showed that in Type 1 under poor control, Ca and PTH were lower (p = 0.03), while uCa was higher (p = 0.003), and after improved control, only uCa continued to be higher (p = 0.035). These findings suggest that increased uCa excretion in association with 'functional hypoparathyroidism' (especially in Type 1 diabetes) is observed during poor blood glucose control, and may be one of the factors leading to reduced bone mass in diabetes mellitus. PMID- 8508618 TI - High prevalence of diabetes in chronic leg ulcer patients: a cross-sectional population study. AB - In a cross-sectional survey, designed to detect all patients with current chronic leg ulcers, 27% of the patients had diabetes mellitus. The outcome for the 104 examined diabetic patients has been evaluated and compared with the 278 nondiabetic patients. The purpose was to establish the prevalence of leg ulcers among diabetic patients and to assess potential causes. The point prevalence was calculated by extrapolating the leg ulcer frequency to the total diabetic population in the studied area. The point prevalence for active leg ulcers (including foot ulcers) in diabetic patients was 3.5% (95% CI 2.8-4.2). Ulcers above the malleoli were almost as common as foot ulcers. Peripheral vascular disease was present in 67% of all ulcerated legs in patients with diabetes compared to 42% in nondiabetic patients (p < 0.001). In 72% of foot ulcers in diabetic patients arterial impairment was judged to be a contributing aetiological factor and in nondiabetic patients 45% (p < 0.001). Ulcers solely attributed to possible neuropathy were less common (15%). Ulcers with multifactorial causes were common above the malleoli. This survey has given the size of the problem and indicates macroangiopathy to be the dominating factor responsible for slow or nonhealing ulcers in diabetic patients. Objective assessment of arterial circulation is mandatory and signs of arterial impairment require consultation with a vascular surgeon. PMID- 8508619 TI - A simple economic evaluation model for selecting diabetes health care strategies. AB - The aim of this work was to develop a simple model to evaluate the health care cost of diabetes in order to help decision-makers in selecting strategies for the prevention, control, and treatment of the disease. The model assesses the cost of full coverage of health care of diabetic patients free of chronic complications and in comparison with those of the treatment of acute and chronic complications. For that purpose, standardized cost figures were obtained from both annual control and treatment of uncomplicated diabetic patients and the treatment of one episode of ketoacidosis, acute myocardial infarction, and amputation of two toes. The treatment/prevention cost ratio obtained showed that prevention of a single episode of any of these late-complication-related events would provide enough funds to cover either the total or partial annual cost of control and treatment of several uncomplicated diabetic patients. These facts would favour the allocation of funds in such a way as to allow adequate control and treatment of diabetic patients to keep them free of the chronic complications of the disease. This would be a wise investment of funds, which would result in a reduction in the socioeconomic cost of the disease and in a better quality of life for the diabetic patients and their families. PMID- 8508620 TI - The effect of acarbose on blood glucose profiles of type 2 diabetic patients receiving insulin therapy. AB - Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 +/- 8.7 (SEM) to 16.7 +/- 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 +/- 6.7 (p > or = 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA1C was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met. PMID- 8508621 TI - Diabetes mellitus and employment: survey of a New Zealand workforce. AB - A cross-sectional survey of a 5670 multiracial New Zealand workforce aged > 40 years was used to determine the health status of people with diabetes mellitus in employment. One hundred and two workers (73 men, 29 women) had known diabetes mellitus (prevalence of 1.8%) of whom 91 individuals (89.2%) had Type 2 diabetes. Mean age of diabetic workers was 51.1 +/- 5.6 (SD) years and median duration of disease was 5.0 (range 0-51) years. Most subjects were asymptomatic, although only 31.4% of diabetic workers had fasting glucose concentrations and 35.5% had fructosamine concentrations within the mean +/- 2SD range of a matched control group. Moreover, 22.5% of diabetic participants had fasting hypertriglyceridaemia and 21.6% had microalbuminuria. Ethnicity (non-European vs European) and lack of insulin therapy were the most important predictors of poor glycaemic control. We advocate more aggressive therapy with insulin and with culturally sensitive education programmes to avert long-term macrovascular complications. PMID- 8508622 TI - Diabetes mellitus and employment: is there discrimination in the workplace? AB - The employment record of 102 diabetic workers (73 men, 29 women), identified in a cross-sectional survey of 5670 middle-aged people in a New Zealand workforce, was studied for evidence of discrimination in the workplace. Compared with 403 matched controls (292 men, 111 women), diabetic workers showed no significant differences in socioeconomic status, educational attainment, or distribution between occupational groups. Similarly, mean duration of current employment (12.3 vs 12.4 years), mean number of jobs in the past 5 years (1.25 vs 1.34 jobs), frequency of sickness absence, and mean number of hours worked each week (43.5 vs 43.3h) did not differ significantly between diabetic and non-diabetic groups. We found no significant differences in work stress, even among those diabetic individuals with poor blood glucose control. There was no convincing evidence across a broad spectrum of industry that diabetic workers did suffer discrimination in the workplace. PMID- 8508623 TI - A single visit diabetes complication assessment service: a complement to diabetes management at the primary care level. AB - Modern diabetes management emphasizes the early detection and prompt treatment of diabetic complications. However it is difficult to organize comprehensive screening at the primary care level. To address this problem we established a complication assessment service whereby all the major diabetes-specific complications were assessed in a single 3 h visit. A report with results and recommendations was sent to the general practitioner (GP). Being philosophically a complication-specific service, no attempt was made to intervene with metabolic management. This paper describes our experience with the first 743 patients of whom 92% had been referred from GPs. Of the diabetes-specific complications, 22% of patients had one, 5% had two, and 1% had three major complications. Many of the patients were unaware of the presence of these complications. One hundred and three people had attended the service on more than one occasion with an average time between visits of 1.7 years. The results demonstrated that GPs were very good at following a recommendation to refer a patient for ophthalmic assessment (85% of cases) and improving hypertension but were less successful in treating hyperlipidaemia. This service has proven to be an excellent forum for the collection of data and the teaching of health professionals. It is a move away from the traditional format of hospital-based clinics providing comprehensive diabetes management. PMID- 8508624 TI - Monitoring the targets of the St Vincent Declaration and the implementation of quality management in diabetes care: the DIABCARE initiative. The DIABCARE Monitoring Group of the St Vincent Declaration Steering Committee. AB - The St Vincent Declaration, a joint initiative on diabetes care and research of the World Health Organization (Europe) and the International Diabetes Federation (Europe), includes 5-year targets for improvement in diabetes outcomes as a central tenet. Accordingly, the establishment of state of the art monitoring and control systems is urged as a basis for the implementation of quality management. As a prerequisite for both targets, a diabetes dataset (fields and definitions) has been agreed to allow common monitoring of diabetes throughout Europe. This dataset has been further developed as the foundation stone of DiabCare, an initiative for continuous quality development in diabetes care. In a formal consensus process using the Delphi method, over 130 European diabetologists from 21 countries contributed to the development of this dataset, which includes fields covering true patient outcomes, intermediate metabolic outcomes, markers of diabetes tissue damage, risk factors, pregnancy, and life-style. The tools for documentation of the quality of health status have been developed in three formats for use in different health care settings. These tools, the DiabCare Diabetes Dataset, the DiabCare Basic Information Sheet, and the DiabCare Computer Program, are designed to allow local feedback-driven improvement in the quality of care, but are also the subject of communication protocols to compare performance between centres, regions, and countries. Whether implemented with or without the benefits of modern information technology, these initiatives can be the basis for both monitoring the targets of the St Vincent Declaration and for implementation of continuing quality development in diabetes care. PMID- 8508625 TI - A dataset to allow exchange of information for monitoring continuing diabetes care. The Diabetes Audit Working Group. PMID- 8508626 TI - Increased insulin requirement in a patient with type 1 diabetes on rifampicin. PMID- 8508627 TI - Chromium, nickel and cobalt contents of some Australian cements. AB - The total chromium, nickel and cobalt concentrations of 8 Australian Portland cements ranged from 49 to 99 micrograms/g, 5 to 54 micrograms/g and < or = 1 to 13 micrograms/g, respectively. The water-soluble chromate concentrations of the cements ranged from 0.2 to 8.1 micrograms/g, and the sodium sulphate-extractable chromates from 1.4 to 9.7 micrograms/g. Results for water-soluble nickel (< or = 0.2 microgram/g) and cobalt (< or = 0.05 microgram/g) indicate that the metals are present only as water-insoluble compounds. The significance of the various data is considered from a dermatological point of view. Cement extracts for the analysis of water-soluble hexavalent chromium (chromates) are stable for at least 12 days. The optimum extraction time for hexavalent chromium in cement appears to be 1 h. Almost 100% reduction of hexavalent chromium is possible after 1 h using 100x the stoichiometric value of iron (II) sulphate. The chromates can become gradually insolubilized when the solution from the water added is in direct contact with the cement, i.e., over a period of > 60 min to 7 days, even without the addition of iron (II) sulphate. PMID- 8508628 TI - Ectopic contact dermatitis from ethyl cyanoacrylate instant adhesives. AB - Although allergic reactions to cyanoacrylate adhesives are extremely rare, they should not be considered impossible. We report a young hairdresser who developed an occupational allergic contact dermatitis to 2 "instant glues" used to attach false hair. The eczematous eruption involved the fingers and face slightly but mainly the eyelids. Patch test reactions were strongly positive to ethyl cyanoacrylate adhesives. PMID- 8508629 TI - Effect of processing cement to concrete on hexavalent chromium levels. AB - Hexavalent chromium sensitization is known to occur from exposure to cement. Concrete is a mixture of cement, sand, rock, and water. Admixtures are compounds used to retard or accelerate concrete setting time. Some countries use ferrous sulfate to reduce hexavalent chromium in cement. We evaluated and compared hexavalent chromium levels in cement, rock (aggregate), and wet and dry concrete in samples from Singapore, Ireland, Denmark, Australia, and the United States. Cement from Denmark contains ferrous sulfate. The effect of representative admixtures on hexavalent chromium concentration in concrete was also evaluated, but technical limitations made evaluation difficult. Soluble chromium levels in cement ranged from 0.225 mg/kg in the US sample to 0.036 mg/kg in the Singapore sample. Aggregate chromium levels ranged from 0.083 mg/kg in the Denmark sample to < 0.002 mg/kg in the Ireland sample. Fresh US concrete, with 1.27 mg/kg hexavalent chromium, contained the highest level. The Denmark sample, with ferrous sulfate added, was lowest (< 0.01 mg/kg). Hardened concrete levels ranged from 0.104 mg/kg from the Ireland sample to 0.002 mg/kg from the Singapore sample. Therefore, hexavalent chromium levels do appear to be influenced by admixtures and by processing from powdered cement to dry concrete. Ferrous sulfate significantly reduced hexavalent chromium levels in fresh cement. PMID- 8508630 TI - Contact sensitivity and cross-reactivity of budesonide. AB - 5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed. PMID- 8508631 TI - The performance of specialized collections of bisphenol A epoxy resin system components in the evaluation of workers in an occupational health clinic population. AB - Epoxy resin of the bisphenol A type (ERBA) is a common cause of occupational contact dermatitis. 167 patients with a history of potential exposure were patch tested with epoxy resin (molecular weight 340) (ERBAM) 1% in pet. and with a number of other ingredients in ERBA systems. 18% of the test patients exhibited a positive response to ERBAM. Phenyl glycidyl ether was the most frequent system component other than ERBAM itself to elicit a positive response (6.1%). Approximately 80% of those tested were unresponsive to ERBAM or any other of the system components, while 20% exhibited a positive response to one or more of the test materials. Only a small % were positive to system materials, but negative to ERBAM, in keeping with previous studies. The study suggests that there is a marginal benefit to testing with other than ERBAM 1%, except in instances where there is known exposure to another ERBA system ingredient, in which event, the patient should also be tested with the specific material to which they have been exposed if there is no response to ERBAM. PMID- 8508632 TI - Occupational contact allergy to unsaturated polyester resin cements. AB - 6 men contracted occupational allergic contact dermatitis from unsaturated polyester (UP) cements. 4 of the men were employed in car repair painting and the remaining 2 in mold manufacturing. The exposure time to UP cements ranged from 6 to 32 years before onset of skin symptoms. All patients had eczema on their hands; in addition, 4 had skin symptoms on airborne areas, i.e., wrists, neck and face. All 6 patients developed allergic reactions when patch tested with UP resin at 0.5-10% in petrolatum (pet.). None of the tested patients reacted to auxiliary or cross-linking chemicals of the cements. Diethylene glycol maleate (DGM) was purified and identified from the UP resin of a cement. 1 patient reacting to UP resin was also patch test positive to DGM and he produced an allergic reaction to DGM down to a concentration of 0.0032% pet. DGM was found in both uncured and cured UP resin. None of the patients could continue their work with UP cements after their sensitization. PMID- 8508633 TI - Patients with atopic eczema do become sensitized to contact allergens. AB - Sensitization to contact allergens in atopics was assessed by grouping 989 patients, who were routinely patch tested, by their personal atopic status. Sensitization to > or = 1 allergens occurred in 38% of the 191 patients with existing atopic eczema, in 53% of the 120 with a past history of atopic eczema, in 54% of the 156 with only mucous membrane atopy and in 50% of the 510 who were not atopic. Sensitization to perfume, a common environmental allergen, was similar in all 4 groups, as was nickel among women. Patients with atopic eczema should be patch tested. PMID- 8508634 TI - The allergenicity of glycerol esters and other esters of rosin (colophony). AB - To investigate whether esterification of rosin with polyalcohols changes its allergenic potential, abietic acid, the main component of rosin, was esterified with glycerol at high temperature. The major product formed was isolated and identified, using nuclear magnetic resonance (NMR), infra-red (IR) and mass spectrometry (MS) analyses, as glyceryl triabietate (GTA), an ester between one glycerol molecule and 3 abietic acid molecules. According to animal experiments GTA was not allergenic and no cross-reactivity was seen to allergens in unmodified rosin. When testing patients allergic to unmodified rosin, no reactions were found to GTA. Some of the patients reacted to glycerol- and pentaerythritol-esterified rosins. According to HPLC analyses, these esterified rosins still contained unmodified material to which the patients may have reacted. It seems that the esterification of rosin with polyalcohols such as glycerol reduces its allergenic activity, possibly because of the formation of much larger molecules with reduced bioavailability. However, making methyl esters of rosin causes little alteration in the molecular weights of the components and, when unmodified and methylated rosin were tested in patients, we saw no difference between the 2 forms. PMID- 8508635 TI - Studies of new short-period method for delayed contact hypersensitivity assay in the guinea pig. (I). Development and comparison with other methods. AB - A new method for delayed contact hypersensitivity assay of chemical compounds in guinea pigs, a short-period method (14 days) with a high detection sensitivity, has been developed. The new method was as follows; a combination of a Freund's complete adjuvant (FCA, undiluted) intradermal injection and a 24-h occlusive patch on a guinea pig was performed 2x at an interval of 4 days and challenged by non-occlusive topical application 11 days after the first sensitization (with benzyl alcohol during test development). Acanthosis and spongiosis in the epidermis and mononuclear cell infiltration into the dermis were observed histopathologically at the skin reaction site. This newly developed method (adjuvant and 24-h occlusive patch 2x test: AP2 test) could equally and/or better detect the allergenicities of 6 other chemical compounds (bromostyrol, citronellal, benzyl salicylate, p-aminobenzoic acid ethyl ester, p phenylenediamine and formaldehyde) as compared with the cumulative contact enhancement test (CCET) and the guinea pig maximization test (GPMT). PMID- 8508636 TI - Photoaggravated allergic contact dermatitis due to topical thiabendazole. PMID- 8508637 TI - Comparison of TRUE Test and Finn Chambers in construction workers. PMID- 8508638 TI - Contact allergy to Osmaron B in milking fat. PMID- 8508639 TI - Artefactual irritant contact dermatitis. PMID- 8508640 TI - Multiple contact sensitivity to eyedrops. PMID- 8508641 TI - Contact urticaria from latex in a patient with immediate hypersensitivity to banana, avocado and peach. PMID- 8508642 TI - Contact urticaria from a worm (Nereis diversicolor). PMID- 8508643 TI - Allergic contact dermatitis from topical mafenide. PMID- 8508644 TI - Contact dermatitis from nylon 6 in Japan. PMID- 8508645 TI - Occupational contact dermatitis from triglycidyl isocyanurate in a powder paint sprayer. PMID- 8508646 TI - Allergic contact dermatitis from pyridine in Karl Fischer reagent. PMID- 8508647 TI - Allergic contact dermatitis from multiple sources of MCI/MI biocide and formaldehyde in a printer. PMID- 8508648 TI - Dithranol-induced erythema sparing hypopigmented lesions of pityriasis versicolor. PMID- 8508649 TI - Contact allergy to topical budesonide in nasal spray. PMID- 8508650 TI - Disulfiram-induced recall of nickel dermatitis in chronic alcoholism. PMID- 8508651 TI - "Where have all the children gone"? Inpatient pediatric care in Connecticut. AB - Admission of children to hospitals in Connecticut dropped precipitously from 1981 to 1991. Regionalization of pediatric inpatient care is happening without plan. Connecticut data show a change in case-mix of pediatric cases, especially in surgical services and child mental illness categories. Planning for pediatric inpatient services should include considerations of case-mix, cost, and especially, quality of care in general hospital pediatric units with very low volume. PMID- 8508652 TI - Tuberculin reactivity is low among residents of a Connecticut nursing home. AB - Of 131 residents of a suburban New England intermediate and skilled nursing facility, 126 agreed to be evaluated by two-stage administration of purified protein derivative (5TU) for tuberculin reactivity. Only eight patients (6.4%) had a positive reaction, considerably fewer than reported by most previous studies. There were no statistically significant differences between reactors and nonreactors based in age, gender, or length of stay in the facility. There was a tendency toward an association of presence of risk factors and a positive response to tuberculin skin testing, but this did not achieve statistical significance (P = 0.063). PMID- 8508653 TI - The Connecticut State Medical Society and malpractice. The first 180 years. PMID- 8508654 TI - Nitrate tolerance--mechanisms and prevention. AB - Nitrate tolerance is of significant clinical concern and every effort should be made to avoid this undesirable effect. The mechanism of tolerance is not clear but probably is multifactorial. Although ACE inhibitors, diuretics, and NAC have been tried as preventative measures, the only method proven to maintain nitrate effectiveness in patients is a nitrate-free interval. The results of further studies designed to determine the actual period of time that the patient is protected will be helpful. This may guide us in choosing the optimal nitrate therapy. PMID- 8508656 TI - Medicine and the war. 1943. PMID- 8508655 TI - Rising health care costs: disease or symptom? PMID- 8508657 TI - Medicare mess. PMID- 8508658 TI - Doctors, patients, and the end of life. PMID- 8508660 TI - In response to Dr. Ahamed. PMID- 8508659 TI - Health-care reform and long-term care. PMID- 8508661 TI - Keep the primary care physician in the hospital. PMID- 8508662 TI - "Attractive educational brochures". PMID- 8508663 TI - The TCu-380A (AG), MLCu375, and Nova-T IUDs and the IUD daily releasing 20 micrograms levonorgestrel--four pillars of IUD contraception for the nineties and beyond? AB - With recent studies repeatedly showing results clearing the IUDs from their formerly suspected role in causing pelvic inflammatory disease (PID), very likely IUD use will further increase worldwide. While most previous IUDs have been withdrawn from the US market during the 1980s, newer and more effective IUDs have subsequently been developed; and some, marketed. Four of these devices will probably become the pillars for future IUD contraception worldwide. This review evaluates the relative performance and safety of these four devices. Consistent findings have proven the Copper-T 380A (Ag) and the Multiload-375 (MLCu375) IUDs to be safe with high and long-lasting efficacy. The Nova-T IUD showed favorable results in some studies, but showed deteriorated efficacy after three years of use in others; more studies are needed. Studies show that the IUD that daily releases 20 micrograms levonorgestrel (LNG-20) is associated with the highest efficacy in preventing accidental pregnancy among the four devices, but it has a uniquely high medical removal rate because of amenorrhea. This steroid-releasing device could be a high-performance IUD if this type of medical removal can be reduced through patient counseling devised according to local cultural background. PMID- 8508664 TI - Copper release from copper intrauterine devices removed after up to 8 years of use. AB - We studied the copper-releasing ability, weight and microscopic appearance of 2 copper-bearing intrauterine devices (IUDs), Copper-T Cu 200 (CuT) and Nova-T Cu 200 Ag (NovaT), after they had been in utero for up to 8 years. In addition, we studied whether IUDs removed from pregnant women showed different copper release. We found that IUD weight was a linear, negative function of duration of use, and that less than 20% of total copper would be released over a period of 8 years. The average copper-releasing ability was significantly higher for CuT than for NovaT (82.6 +/- 6.4 vs. 42.7 +/- 2.6 micrograms/day). The copper release was constant and thus unrelated to duration of use. Copper-releasing ability was similar in IUDs removed from pregnant and non-pregnant women. Fragmentation or minor defects only occurred in 3% of the IUDs and no correlation was found between deposits or corrosion and copper release rates. We conclude that CuT and NovaT both have constant copper release for at least 5-6 years and that the useful life-span probably can be prolonged to 6-8 years or more. PMID- 8508665 TI - A national study to monitor the safety of IUCD use. AB - OBJECTIVE: To determine whether the known adverse effects of IUD use were being kept to a minimum in a population of women. DESIGN: A national survey of all doctors purchasing IUDs in a three-month period. Information was sought on the doctors' training, experience and usual insertion practice, and also on characteristics of each woman receiving an IUD in the study period. MAIN OUTCOME MEASURES: Published national and international guidelines on selection of users for IUDs and on training for IUD insertion were compared with our findings on these measures. RESULTS: Not all IUD insertions were in accordance with published guidelines. Very few IUD insertions (0.9%) were carried out in the face of absolute contraindications to this type of contraception. However, 126 insertions (27%) were for women who had a relative contraindication, excluding an incomplete family. Gynaecologists were significantly less likely to fit an IUD in the presence of contraindications than other doctors. Few doctors reported training to the standard recommended. CONCLUSIONS: That the known adverse effects of IUD use are not being kept to a minimum for New Zealand women. The study design could be used to estimate the potential for adverse effects in populations for other types of contraceptives. PMID- 8508666 TI - Effect of four combined oral contraceptives on blood pressure in the pill-free interval. AB - OBJECTIVE: To evaluate blood pressure changes in the pill-free interval and from baseline among women taking four different low-dose monophasic oral contraceptives. DESIGN: 131 women were randomized to four different oral contraceptives. Pressures were obtained at baseline, at the end of treatment cycles and at the end of the 7 pill-free days, during 6 months of treatment. Pressures were obtained at 4 and 8 weeks after discontinuation. Group 1 received norethisterone acetate 1000 micrograms, group 2 received levonorgestrel 150 micrograms, group 3 received desogestrel 150 micrograms, and group 4 received gestodene 75 micrograms, all combined with ethinyloestradiol 30 micrograms. RESULTS: All four groups showed an increase in pressure during treatment, with return to baseline levels four weeks after treatment. At the end of the pill-free interval, the readings did not differ significantly from on treatment except for women in Group 4, who experienced an increase in diastolic pressure. CONCLUSIONS: Use of the four oral contraceptives was associated with a small increase in systolic and diastolic pressure. Whatever mechanism causes the increase is not entirely reversible by 7 days without treatment. PMID- 8508667 TI - The effect of the male contraceptive agent gossypol acetic acid on mouse bone marrow cells in vivo: micronuclei and mitotic index. AB - In this work the genotoxic effect of gossypol acetic acid (gossypol) was evaluated by determining the frequency of micronuclei and mitotic index in male mouse bone marrow cells in vivo. Bone marrow cells were collected at 24th hour after the single intraperitoneal (20, 40, and 80 micrograms/g) administration of gossypol. Polychromatic erythrocytes (PCEs) in the bone marrow were then evaluated with respect to micronuclei frequency. The dose-dependent increase in the micronuclei frequency was observed. However, when compared with the control group, the increase was not found to be significant (P > 0.05). Also the mitotic index values were not found to be different from those control values (P > 0.05). The results suggest that gossypol is not a clastogenic and mutagenic agent in mouse bone marrow cells in vivo. PMID- 8508668 TI - Male antifertility compounds from Tripterygium wilfordii Hook f. AB - Extracts of the Chinese medicinal plant, Tripterygium wilfordii, cause reversible infertility in male animals. Sub-fractionation studies have now revealed that the plant extracts contain a number of compounds which are potent antifertility agents in male mammals, including the diterpenes triptolide and tripdiolide and an isomer of the latter. A triptolide, 12,13-chlorohydrin, which is a transformation product formed reversibly by interaction of triptolide with HCl, was also found to be active. PMID- 8508670 TI - Postcoital use of anordrin and RU 486 for prevention of implantation in the rat. AB - Because RU 486 synergizes with anordrin and its dihydroxylated metabolite to terminate established pregnancy in the rat and rabbit, the interactions of these agents were studied at two days postcoitally in the rat. RU 486 at a dose of 4 mg/kg did not prevent pregnancy when the animals were killed 12 days post insemination. A 2.5 mg/kg dose of anordrin prevented pregnancy in 14% of animals. By contrast, none of the animals became pregnant when treated with 2.5 mg/kg of anordiol. A non-effective dose of RU 486 (2 or 4 mg/kg) combined with a non effective dose of anordrin (1.25 or 2.5 mg/kg) prevented pregnancy in all animals treated; there was no evidence of implantation sites or embryos when the animals were killed on day 12 post insemination. The same synergistic effect was observed when a small dose of RU 486 (e.g., 1 mg/kg) was combined with 0.6 mg/kg anordiol. To investigate the mechanism of pregnancy prevention, animals were treated two days postcoitally with 4 mg/kg of RU 486 plus 2.5 mg/kg of anordrin or 2 mg/kg of RU 486 plus 0.6 mg/kg of anordiol and were killed short intervals after treatment. These drugs had no effect by 6 h, but the numbers of embryos in oviducts were significantly reduced 12 h after treatment. By 24 h following treatment, no embryos were recovered from either the oviduct or the uterus. Progesterone and estradiol levels in serum collected 24 h after treatment were not significantly different from those of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508669 TI - Spermicidal activity of an antifungal saponin obtained from the tropical herb Mollugo pentaphylla. AB - The ethyl acetate fraction of Mollugo pentaphylla, a tropical herb, contains an antifungal saponin (mollugogenol-A). We report here the spermicidal effects of this saponin. Washed sperm (> 100 x 10(6) with > 50% motility) from normal volunteers were incubated with varying concentrations (0-300 micrograms/ml) of mollugogenol-A at 30 degrees C. Sperm motility, velocity and viability were assessed at 0, 30, 60 minutes both manually and by using computer assisted semen analysis (CASA). Samples collected at 0 and 60 minutes were evaluated for membrane lipid peroxidation, superoxide dismutase (SOD) activity and transmission electron microscopy. A dose- and time-dependent effect of this saponin on sperm motion and viability was observed. The maximal spermicidal effect (4-5 fold decrease in motility and viability) was observed with 300 micrograms/ml dose of saponin. A three-fold increase in sperm membrane lipid peroxidation with corresponding inhibition of SOD activity were observed after 60 minutes incubation with this spermicidal agent. Transmission electron microscopy of saponin-treated samples revealed significant damage to the sperm membrane in both head and tail regions, and the acrosomal membranes were notably swollen and disrupted. These results indicate that this natural saponin has a potential spermicidal effect besides its known antifungal activity. The likely mechanism of its action involves sperm membrane damage by increased lipid peroxidation. PMID- 8508671 TI - Contraceptive steroids increase erythrocyte lipid peroxidation in female rats. AB - In order to investigate the effects of contraceptive steroid combinations on lipid peroxidation in the erythrocyte membranes, adult female rats were divided into 2 groups for short- and long-term investigations; each group was then subdivided into 5 subgroups according to orally given low and high doses of EE/NEA (ethinyl estradiol/norethisterone acetate) and EE/LNG (ethinyl estradiol/levonorgestrel) combinations and control group. Since EE was included in each combination, the groups were named according to the progestin (NEA, LNG) components. At the end of the experiment periods, lipid peroxidation in the erythrocyte membranes from rats was measured. When compared to the controls, except low-dose LNG groups, lipid peroxidation levels were increased in all study groups. It was seen that the effect of NEA and LNG combinations on lipid peroxidation was not time-, but dose-dependent. When these combinations were compared to each other, different effects of NEA and LNG on lipid peroxidation were not detected in the experiment period. As a result, the increased lipid peroxidation following the administration of contraceptive steroid combinations is a very important finding that should be taken into account, in addition to the effects of these steroids on lipid and lipoprotein metabolism. PMID- 8508672 TI - Confirmation of isochromosome 18p using whole chromosome arm-specific fluorescence in situ hybridization. AB - Fluorescent in situ hybridization (FISH) using a pool of DNA clones that have been mapped to the short arm of chromosome 18 is described. This arm-specific painting technique was used to analyze the chromosomes of two patients who displayed different clinical pictures. One patient had clinical features consistent with tetrasomy 18p, and the other patient had some of the clinical features associated with trisomy 18. The initial karyotype of both patients showed the presence of a small metacentric marker chromosome, thought to resemble an iso(18p). This interpretation of the karyotype was confirmed for both cases using a specific chromosome arm-painting strategy. While whole-chromosome paints may identify the origin of markers or detect translocations, arm-specific libraries will permit detailed analysis of chromosomal rearrangements when more precise information may be needed. PMID- 8508674 TI - Detection of aneuploidy in human interphase spermatozoa by fluorescence in situ hybridization (FISH). AB - Fluorescence in situ hybridization (FISH) with repetitive-sequence DNA probes was performed on human interphase sperm to determine the utility of this technique for aneuploidy detection. DNA sequences specific for chromosomes 15 and 16 and the Y were biotinylated and hybridized with human sperm that had been treated with cetyltrimethylammonium bromide and dithiothreitol to render them accessible to the probes. Fluoresceinated avidin and antiavidin were utilized to visualize bound probe. More than 10,000 sperm were analyzed for each chromosome probe. The hybridization efficiency was 98-99% for all three probes. The frequencies for disomy (i.e., for nuclei containing two fluorescent signals) for chromosomes 15 and 16 and the Y were 0.14%, 0.17%, and 0.11%, respectively. These frequencies are all somewhat higher than those obtained by the human sperm karyotyping technique. Nevertheless, these preliminary results suggest that FISH is a simple and rapid technique that may provide an accurate screen for aneuploidy detection in human sperm. PMID- 8508675 TI - The uptake of uridine in the nucleolus occurs in the dense fibrillar component. Immunogold localization of incorporated digoxigenin-UTP at the electron microscopic level. AB - A new method was developed to localize the site of transcription within the nucleolus. Incorporation of digoxigenin-labeled UTP in nucleoli of human PHA stimulated lymphocytes and in equine melanoma cells was visualized with antibodies against digoxigenin and secondary gold-labeled antibodies at the electron-microscopic level. This approach offers much higher spatial resolution than the autoradiographic methods used so far. In both types of cells digoxigenin UTP was incorporated mainly into the dense fibrillar component; the fibrillar centers, in contrast, did not display significant labeling above background levels. This finding corroborates the view that the dense fibrillar component is the site of RNA transcription in the nucleolus. PMID- 8508673 TI - Isolation of new probes in the region of the Wilson disease locus, 13q14.2- >q14.3. AB - A hybrid panel was used to refine the localizations of eight established markers useful for the diagnosis of Wilson disease. Two of the markers, D13S59 and D13S31, that map very close to the Wilson disease locus (WND) were localized to the region 13q14.2-->q14.3. We report the isolation of seven new probes from this region, using two different approaches. First, 16 clones from a chromosome 13 specific library were mapped using the hybrid panel. Three of the clones mapped to 13q14.2-->q14.3. As a second approach, Alu element-mediated PCR (Alu-PCR) was used to generate clones from a hybrid (ICD) that contains the proximal half of chromosome 13 as the only human component. To select for those that potentially mapped within the region 13q14.2-->q14.3, the clones were screened by differential hybridization using the labeled Alu-PCR products from a hybrid (KSF39) that is similar to ICD but has a deletion in the region 13q14.2-->q14.3. The procedure was successful even though KSF39 contains five additional human chromosomes. Six independent clones were selected. Five of these were found to be nonrepetitive, and four were found to map correctly to 13q14.2-->q14.3 when localized using the hybrid panel. PMID- 8508676 TI - Localization of the gene encoding proteinase-3 (the Wegener's granulomatosis autoantigen) to human chromosome band 19p13.3. AB - Proteinase-3 (PR3) is a polymorphonuclear leukocyte serine proteinase that is a potent inducer of emphysema in experimental models. PR3 is also the target antigen associated with Wegener's granulomatosis. By analysis of a panel of somatic cell hybrids, the gene encoding PR3 was localized previously to chromosome 19; we have used fluorescence in situ hybridization to sublocalize this gene to 19p13.3. PMID- 8508677 TI - High-resolution cytogenetic analysis of X-ray induced mutations of the HPRT gene of primary human fibroblasts. AB - We report cytogenetic analysis of X-ray induced mutants of the HPRT gene isolated from a primary human fibroblast line. The mutants were shown previously by molecular analysis to have total or partial HPRT gene deletions. Detailed analysis of the chromosomal region containing HPRT (the cytogenetic band Xq26) identified Xq26 aberrations in five of five total HPRT gene deletions but failed to detect any changes in two of two partial gene deletions. Four microdeletions were verified and quantified by a method termed the band ratio, which compares the distance between bands encompassing Xq26 and an adjacent X-chromosome region in elongated chromosomes. These measurements were supported by the presence or absence of the sub-band Xq26.2. One total HPRT gene deletion was also associated with an X;11 translocation involving band Xq26. The data strengthen earlier findings on the tolerance of the Xq26 region to large genetic changes (> 1 Mb), but also indicate that some mutations are more complex than simple deletion of DNA sequence. PMID- 8508678 TI - Linkage mapping detects two secondary microdeletions in cell hybrid HHW1064, used to isolate DNA probes from within 5q11.2-->q13.3. AB - The somatic cell hybrid HHW1064 contains a single human chromosome 5 with an interstitial deletion for 5q11.2-->q13.3. Twenty human clones were isolated by Alu-PCR differential hybridization. Mapping these clones indicates that HHW1064 contains two additional secondary microdeletions. PMID- 8508679 TI - Fine mapping of the human MHC class II region within chromosome band 6p21 and evaluation of probe ordering using interphase fluorescence in situ hybridization. AB - Eight previously well-characterized and mapped probes derived from the human major histocompatibility complex (MHC) class II region were used to investigate the advantages and limitations of fluorescence in situ hybridization (FISH) techniques for fine mapping. The class II region of the MHC was localized within subband 6p21.31 by in situ hybridization on metaphase chromosomes that were banded by immunofluorescence staining with an antibody against 5 bromodeoxyuridine (BrdU). Ordering of probes that were separated by up to 900 kb was achieved by simultaneous hybridization of two or three probes on interphase nuclei. Three-color FISH proved to be an excellent method for ordering of probes within distances of 200-1,000 kb. Under certain conditions, closer probes could be ordered by comparing measured distances between their hybridization signals in interphase nuclei. A linear correlation between measured interphase distances and kilobase distances was observed up to 500 kb. With increasing distances, the measurements become more inaccurate due to chromatin folding. PMID- 8508680 TI - Isolation of 353 NotI-linking clones and 62 DNA markers (DXS607-DXS668) from human chromosome Xq24-->qter. AB - Through restriction enzyme digestion of 1,784 cosmid DNAs derived from human chromosome region Xq24-->qter, we identified 353 NotI-linking cosmids (11 individual groups of overlapping NotI-linking cosmids at Xq24-->q25.6 groups at Xq26-->q27, and 19 groups at Xq28). Sixty-two of the 353 clones (DXS607-DXS668) contained multiple rare-cutter sites, including multiple SacII sites within a 2 kb region, as well as one to six sites for BssHII, MluI, NotI, or NruI. PMID- 8508681 TI - Comparison of mouse Y-chromosomal repetitive sequences isolated from Mus musculus, M. spicilegus, and M. spretus. AB - The mouse Y chromosome is rich in repetitive sequences. We describe a new highly male-specific BALB/c mouse sequence named 142-5. The distribution of 142-5 related sequences, which appeared to be repeated at least 100 times in the male genome of Mus musculus, was visualized on the Y chromosome by in situ hybridization. Their accumulation patterns in the genus Mus showed that the sequences evolved quickly and suggested that they might prove useful for detecting genetic differences between closely related species. To test this hypothesis, we isolated 20 additional sequences from three mouse species (M. musculus, M. spicilegus, and M. spretus) and compared their nucleotide sequences using three different computer programs. It was found that the sequences were remarkably similar but could be divided into four subgroups, and that each species had a distinct set or sets of sequences that were amplified in the Y chromosome. PMID- 8508682 TI - Assignment of the beta subunit of the muscle nicotinic acetylcholine receptor gene (CHRNB1) to sheep chromosome 11. AB - The chromosomal assignment of the gene for the beta subunit of the sheep muscle nicotinic acetylcholine receptor (CHRNB1) was determined by isotopic in situ hybridization. CHRNB1 was mapped to sheep chromosome 11, with a hybridization peak at 11q14-->q22. This result is further evidence that the chromosomal segment that comprises human chromosome 17 has been highly conserved during evolution. PMID- 8508683 TI - Mapping of the human spermidine synthase gene (SRM) to 1p36 and a probable pseudogene (SRML2) to region 3p14-->q21. AB - Using Southern blot analysis of panels of human podent somatic cell hybrids and chromosomal in situ hybridization, we have been able to assign human spermidine synthase DNA sequences to 1p36 (SRM) and 3p14-->q21 (SRML2). Present data suggest that the former chromosomal site harbors the functional gene and the latter site only a pseudogene. PMID- 8508684 TI - Complementation analysis in ataxia telangiectasia: fibroblast-lymphoblastoid cell heterokaryon assay by radiation-induced chromosome aberrations. AB - Using radiation-induced chromosome aberrations as a marker, heterokaryons of ataxia telangiectasia formed between appropriate combinations of lymphoblastoid cell lines (LCLs) and fibroblasts representing four and two different groups, respectively, were analyzed. The results showed that complementation group 2 in the LCL series corresponds to group D in the fibroblast series. PMID- 8508685 TI - Ultrastructural alterations of bacteria during the postantibiotic effect. AB - Ultrastructural alterations of Staphylococcus aureus and Pseudomonas aeruginosa were examined during the postantibiotic effect (PAE) with transmission electron microscopy. After exposure to dicloxacillin the staphylococci were characterized by an increase in the number of crosswalls, rifampin produced thickening of the cell wall, but only minimal changes were induced by gentamicin. Intracellular electrondense aggregates were observed in P. aeruginosa after exposure to imipenem, tobramycin and ciprofloxacin, and imipenem caused globoid cell formations. These alterations were not uniform in every organism, but they correlated well with the duration of the PAE determined by viable counts. PMID- 8508686 TI - Antibacterial activity of oral antibiotics against anaerobic bacteria. AB - The spectrum and the antibacterial susceptibility of anaerobic bacteria to oral antibiotics isolated from clinical specimens was assessed in two different centres, the first receiving specimens from University departments and the second from general practitioners and small hospitals. Susceptibility was studied with a microtiter ready-to-use panel system, using the manufacturer's modified Wilkins Chalgren's broth as the test medium for the following antibiotics: ampicillin, ampicillin+sulbactam, amoxicillin+clavulanic acid, cephalexin, cefaclor, cefuroxime, cefetamet, clindamycin, doxycycline and erythromycin. Anaerobic bacteria frequently encountered in clinical specimens from the University departments were mainly resistant Bacteroides spp., especially Bacteroides fragilis, Propionibacterium spp. and Peptostreptococcus spp., whereas in the outpatient center, Peptostreptococcus spp, Actinomyces spp. and Veillonella parvula (usually considered as colonizing flora) represented 90% of the cultured bacteria. The study shows that the members of most Bacteroides spp. encountered in a hospital environment are resistant to most of these agents (except clindamycin, amoxicillin+clavulanic acid, and ampicillin+sulbactam), whereas the gram-positive pathogens are widely covered by most of the orally available agents studied including cefetamet. PMID- 8508687 TI - Comparative antibacterial activity of the aminothiazolyl cephalosporin RU 29,246. AB - A total of 1,007 clinical isolates from a tertiary care center were tested against RU 29,246, ampicillin, cephalothin, cefoxitin, ceftazidime, Augmentin, oxacillin, piperacillin, gentamicin, amikacin and vancomycin. Bacteria tested consisted of 479 strains of Enterobacteriaceae, 64 pseudomonads, 18 Xanthomonas, 42 other gram-negative bacilli, 56 enterococci and 348 isolates of staphylococci. RU 29,246 showed excellent in vitro activity inhibiting > 90% of Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Enterobacter, Proteus mirabilis, Providencia, Morganella, Salmonella, Shigella, Aeromonas hydrophila, and methicillin-susceptible Staphylococcus aureus at an MIC of 0.5-1.0 mg/l. Seventy seven percent coagulase-negative staphylococci had an MIC of 1.0-4.0 mg/l. All strains of Pseudomonas aeruginosa and X. maltophilia were resistant to RU 29,246. Fifty-six percent of the enterococcal isolates were inhibited by 1.0-16.0 mg/l of RU 29,246. PMID- 8508688 TI - Effects of ciprofloxacin on chromosomes, and hepatic and renal functions in rats. AB - In the present study, ciprofloxacin, a fluoroquinolone antibiotic, was evaluated in vivo. The toxic effects of ciprofloxacin (20 and 200 mg/kg/day) on kidney and liver functions, and on chromosomes were investigated in rats. 20 mg/kg/day ciprofloxacin did not significantly affect urine composition, serum enzyme levels and the haematocrit, affecting only creatinine clearance. The 200 mg/kg/day dose increased urine volume, serum creatinine and and creatinine clearance. Ciprofloxacin at both doses had no significant numerical effect on chromosomes, but there was a statistically significant dose-dependent increase in chromatid type breakage. Significant histological changes in the liver and kidney were not observed. PMID- 8508689 TI - Efficacy of prophylactic and early fluconazole treatment on systemic candidiasis in experimentally neutropenic rabbits. AB - The efficacy of prophylactic and early fluconazole treatment on experimental systemic candidiasis was investigated in neuropenic rabbits. Fifteen rabbits were used and divided into three groups: fluconazole was started 24 h before the inoculation of Candida albicans in the first group, and 24 h after the inoculation in the second group. The third group was the control group without antifungal therapy. Prophylactic and early fluconazole treatment for 7 days after C. albicans inoculation did not reduce the mortality and tissue culture positivity in the rabbits significantly. Four of the five rabbits survived 7 days both in the prophylactic and early treatment groups. However, only one rabbit survived for 7 days in the control group. In diagnostic procedures, histopathological examination and evaluation with periodic acid-Schiff stain was found to be the most sensitive. In this study, prophylactic and early fluconazole treatment were found to be insufficient for treatment of systemic candidiasis in neutropenic rabbits. PMID- 8508690 TI - Effect of in vitro acyclovir treatment on selected functions of blood-derived macrophages. AB - The effect of acyclovir (ACV) treatment on selected functions of human blood derived macrophages was examined. ACV was not cytotoxic when applied in a wide range of concentrations. Only minor effects on macrophage functions were observed when cells were treated with therapeutic concentrations of ACV:phagocytosis and the production of interferon and tumor necrosis factor were slightly enhanced, while the production of lysozyme was reduced, in a dose-dependent manner. Interferon production was also reduced in the presence of high concentrations of ACV. PMID- 8508691 TI - Mode of inhibition of respiratory syncytial virus by a plant flavonoid, SP-303. AB - A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was found to have antiviral activity against respiratory syncytial virus (RSV) in the 2-10 microM range in plaque reduction assays and cytopathic-effect-inhibition assays. The material was also virucidal. The 50% effective concentration (EC50) for virucidal activity was 28 microM. Experiments were done to determine the mode(s) of RSV inhibition by SP-303. Interferon was not induced. SP-303 did not inhibit attachment at antiviral concentrations. However, the EC50 for inhibition of virus penetration by SP-303 was 0.48 +/- 0.19 microM. These data suggest that abolition of RSV penetration into host cells is one mechanism whereby SP-303 inhibits RSV replication. PMID- 8508692 TI - Single-dose oral ciprofloxacin plus parenteral metronidazole for perioperative antibiotic prophylaxis in colorectal surgery. AB - From 1983 until 1990 our standard antibiotic prophylaxis in colorectal surgery has been 80 mg gentamicin plus 500 mg metronidazole, both administered intravenously at the beginning of anesthesia, and then 80 mg gentamicin every 8 h for 3 days. In this time period, 718 patients undergoing elective colorectal surgery by abdominal approach were treated with this prophylactic procedure. The mean wound infection rate was 13.4% with no significant differences between years. In the present study, including 100 adult patients, intravenous gentamicin has been replaced by a single oral dose of 750 mg ciprofloxacin randomly administered 1, 2 or 3 h (+/- 30 min) before anesthesia. All other procedures remained unchanged including intravenous metronidazole. In order to correlate an eventual infection with the actual tissue concentrations during surgery, samples of colon, peritoneum, muscle, subcutaneous fat and skin were obtained from all patients and assayed by HPLC. In only 3 cases (3% of them casuistic) was a wound infection observed, 2 of minor importance and 1 case with wound dehiscence. This infection rate is significantly lower than 13.4% obtained with our previous standard regimen, and lower than the 9% wound infection rate considered to be the 'gold standard' for elective colon resections. The effective ciprofloxacin concentrations in tissues were usually notably higher than the MICs of the pathogens commonly observed in surgical infections of colorectal surgery. By far the highest ciprofloxacin concentrations were observed in colon tissue which may explain the absence of anastomotic dehiscence or peritoneal sepsis in our series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508693 TI - Straining at stool and laxative taking in an English population. AB - A population-based sample of 834 men (ages 40-69 years) and 1058 women (25-29 years) was investigated with respect to straining to defecate, stool form, bowel habit, and use of laxatives, by means of a questionnaire and a three-stool record form. Straining was common but, contrary to standard teaching, far from universal. It was unrelated to age but was commoner in women than men. Many people underestimated how often they strained. Overall, 32% of defecations in women and 22% of defecations in men were associated with straining to start and 15% and 9%, respectively, with straining to finish. Straining was to some extent related to stool type: the lumpier a stool, the more often it elicited straining. However, it seems likely that straining in some people is just a habit. Use of laxatives was found to be less prevalent than in the past, and most people with evidence of constipation did not use them. Use of laxatives increased with age, and some older people used them inappropriately. The most popular laxatives were based on phenolphthalein, senna, or magnesium. PMID- 8508694 TI - Olestra, a nondigestible, nonabsorbable fat. Effects on gastrointestinal and colonic transit. AB - Olestra, the name proposed for the mixture of hexa-, hepta- and octaesters of sucrose and long-chain fatty acids, is a nondigestible, nonabsorbable lipid with physical properties and taste that are similar to those of natural triglycerides. Our aim was to determine whether substitution with up to 30 g of olestra in a 45 g fat meal would alter gastric, small bowel, and colonic transit. Five groups, each of six healthy volunteers, ingested 800-kcal, 22-g protein meals containing a total of 45 g of lipid (N = 24) or 15 g of lipid (N = 6). Among those receiving the 45-g fat meal, 0, 7.5, 15 and 30 g of lipid were substituted with olestra (N = 6 per group). The 15-g fat meal consisted entirely of natural triglyceride. A dual gamma camera scintigraphic method was used to estimate gastric and small bowel transit (99mTc pellets in the meal) and colonic transit (111In pellets). The latter was achieved by the delayed release of 111In pellets from a capsule coated with a pH-sensitive polymer, methacrylate, that disintegrated in the terminal ileum. There were no differences in the gastric, small bowel, or colonic transits of any of the five equicaloric meals. Some individuals had a significantly greater 48-hr stool weight after ingesting 15 g of olestra, but stool weights of subjects consuming 7.5 g or 30 g of olestra did not differ from controls. We conclude that substitution with olestra of up to 30 g in a 45-g fat meal does not significantly alter gastrointestinal transit in healthy subjects. PMID- 8508695 TI - Effect of nifedipine on mouth-to-cecum transit of liquid meal in normal subjects. AB - Nifedipine has been shown to inhibit small bowel motility and to increase ileal water and electrolyte absorption in animals, but few reports are available in human subjects. The drug has been reported to influence esophageal and colon motility in man, without affecting gastric emptying. We performed a double-blind, controlled, crossover, randomized study to investigate the effect of oral nifedipine 30 mg vs placebo on the orocecal transit time of a lactulose-labeled, liquid caloric meal in nine healthy volunteers, and its correlation with plasma nifedipine concentration. The transit time was measured using the breath hydrogen test. The drug study was preceded by a reproducibility study, which showed a mean variation in transit time of 8.3% (+/- 1%, SE). Nifedipine significantly increased orocecal transit time compared to placebo (nifedipine 131 +/- 16; placebo 104 +/- 14.5 min; P < 0.05). This effect correlated well with plasma nifedipine concentration expressed as area under the curve (r = 0.92, P < 0.004). Nifedipine 30 mg significantly delays orocecal transit of a liquid caloric meal. The small bowel is likely to be the site of action. These findings may afford a rational basis for investigating a possible antidiarrheal role of nifedipine. PMID- 8508696 TI - Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract. AB - We investigated the effect of an erythromycin derivative, EM523L, on interdigestive gastrointestinal motor activity and plasma motilin concentrations in three healthy volunteers using an infused catheter system. We administered doses of 500, 1000, and 2000 micrograms of EM523L to each subject as well as physiological saline. EM523L induced interdigestive migrating contractions (IMCs) that originated in the stomach and migrated to the duodenum. This response was noted in all three subjects after each dose of EM523L, while no IMCs were induced by saline. There were no significant differences in the characteristics of the EM523L-induced IMC and the spontaneous IMC. The initiation time, ie, the interval between the start of EM523L infusion and the onset of the IMC became shorter in a dose-dependent manner. Plasma motilin concentrations increased significantly after EM523L administration, suggesting that motilin is involved in the mechanism of IMC induction by this drug. PMID- 8508697 TI - Oral [111In]DTPA scintigraphic assessment of colonic transit in constipated subjects. AB - Patterns of colonic transit were assessed by a simple radioisotopic technique using 3.7 MBq of orally administered [111In]DTPA in 16 control subjects and 37 patients with intractable constipation. Normal subjects showed rapid diffuse spread of isotope through the colon resulting in low activity in all regions of interest (ROI). Activity was lost to feces at 24 hr and was virtually complete by 72 hr (median 94%, range 71-100%). Five constipated patients showed normal transit. Those with colonic inertia (N = 26) showed a significantly slowed geometric center of isotope compared to controls (P < 0.001), falling below the normal range at 48 hr. Percentage activity curves showed the major site of isotope hold-up to be in the transverse colon and splenic flexure. Other constipated patients (N = 6) showed late delay of the geometric center of isotope and accumulation of activity in the descending and rectosigmoid colon, compared to controls, at 96 hr. Oral [111In]DTPA colonic scintigraphy is a useful clinical test in the investigation of constipation. PMID- 8508698 TI - Impaired colonic motor response to cholinergic stimulation in patients with severe chronic idiopathic (slow transit type) constipation. AB - Chronic idiopathic constipation, especially the slow transit type, is a troubling problem often afflicting young women. The pathophysiological basis for this entity is unknown, although a defective cholinergic innervation has been postulated. We tested the hypothesis that cholinergic colonic innervation is deranged in this condition by studying colonic motor activity after strong cholinergic stimulation with edrophonium chloride in 14 women complaining of slow transit constipation. Unlike healthy subjects, constipated patients showed minimal or no response to edrophonium injection. It is concluded that in slow transit constipation there is an important alteration of colonic cholinergic activity and that edrophonium chloride may represent a useful test drug for colonic pathophysiological investigations. PMID- 8508699 TI - Signal transduction pathways mediating mucin secretion from intestinal goblet cells. AB - Cholinergic stimulation of the HT29-18N2 goblet cell line increased mucin secretion as assessed: (1) with a mucin-specific immunoassay, (2) using whole mount immunocytochemistry, or (3) by morphometric quantification of intracellular mucous granule stores. Cholinergic stimulation did not, however, result in the apical plasmalemmal membrane cavitation that is characteristic of recent compound exocytotic activity. The response was not dependent on protein kinase C activation since it was not inhibited by the kinase C antagonist H7 or potentiated by the diacylglycerol kinase antagonist R59022. Calcium ionophore A23187 also accelerated mucin secretion by a noncompound exocytotic pathway. Activation of protein kinase C by phorbol 12-myristate 13-acetate, on the other hand, increased mucin secretion by a compound exocytotic pathway. The results provide insight into the signal transduction pathways underlying secretory responses of goblet cells observed in situ. PMID- 8508700 TI - Chronic bile diversion does not alter canine interdigestive myoelectric activity. AB - Previous studies have suggested that the cyclic entry of bile into the duodenum during fasting regulates interdigestive patterns of motility by releasing the putative regulatory hormone motilin. Our aim was to determine if cyclic secretion of bile into the duodenum regulates interdigestive myoelectric activity and plasma motilin concentrations. Six dogs were prepared with gastric and intestinal serosal electrodes. Myoelectric activity was measured during fasting and after a meal before and after reoperative translocation of the entrance of the bile duct to the mid-jejunum. The characteristics of the migrating myoelectric complex (MMC) and conversion to a postprandial pattern were similar before and after bile duct translocation. The period (112 +/- 5 vs 109 +/- 10 min; mean +/- SEM), migration velocity of phase III through the duodenum (8.9 +/- 1.2 vs 6.8 +/- 0.5 cm/min), and duration of individual phases of the MMC in the stomach, duodenum, and jejunum were not altered significantly (each P > 0.05) by chronic diversion of bile from the duodenum. Plasma motilin concentrations were similar before and after bile duct translocation (P > 0.05), continued to cycle temporally with the MMC, and peak concentrations occurred during phase III and were greater than during phases I and II (P < 0.01). We conclude that the presence of bile in the lumen of the duodenum does not regulate interdigestive myoelectric patterns of the canine upper gut or the cyclic release of motilin. PMID- 8508701 TI - Effects of enteral infusion of hypertonic saline and nutrients on canine jejunal motor patterns. AB - The aim of the study was to clarify the effects of hypertonic solutions on jejunal motility. The study focused on differential effects of hypertonic saline and nutrients. Motility of the canine proximal jejunum was recorded with closely spaced strain-gauge transducers. During fasting, hyperosmotic solutions (up to 1520 mosmol/liter) of saline or nutrients (1 kcal/ml) were infused into the proximal jejunum (0.5-1.5 ml/min) up to 6 hr. The hyperosmotic solutions stimulated jejunal motility. With both increasing osmolarity of saline or increasing energy load of nutrients, jejunal motility linearly declined. The reduction of motility was associated with a change in motor pattern from a propulsive to a more segmenting one. Hypertonic glucose evoked a significantly smaller level of motor activity compared with both saline (at given osmolarities) and an elemental diet (at given energy loads). Motility parameters were not different between glucose and maltose, although osmolarity of maltose was less than half (760 vs 1520 mosmol/liter). In contrast, a mixture of glucose-fructose exerted a smaller inhibition of jejunal motility than glucose. The hypertonic solutions of saline or nutrients were tolerated over 2 hr; with hypertonic saline retrograde power contractions with or without vomiting occurred, whereas with hypertonic nutrients vomiting was preceded by strong inhibition of jejunal motility. Three conclusions can be derived from the present results: (1) The behavior of jejunal motility suggested that the motor activity was the result of both a local stimulation and an inhibitory feedback mechanism. (2) The different degree of inhibition between glucose and saline indicated that the nutrient itself played a major role in the inhibitory feedback regulation, whereas osmolarity was of minor importance. (3) Comparisons between different nutrients suggested a linkage between inhibitory control of motility and the absorptive capacity of the gut for the single nutrient. PMID- 8508702 TI - Migrating myoelectric complex and jejunal slow-wave propagation after Roux gastrectomy in dogs. AB - Roux-en-Y gastrectomy is associated with a high incidence of symptoms of gastric stasis. Retrograde propagation of jejunal electrical slow waves and spike bursts has been implicated in the Roux Y stasis syndrome. Since the fasted state may persist after feeding, this study examined the extent of retrograde slow-wave propagation in the fasted state, particularly during aboral migration of phase III. Six dogs underwent Roux gastrectomy and placement of bipolar electrodes along the Roux limb. Four normal dogs with electrodes acted as controls. Thirty five migrating myoelectric complexes were recorded in Roux dogs and 13 in controls. In Roux dogs, the incidences of retrograde propagation of slow waves during the migrating myoelectric complex were phase I 56 +/- 13%, phase II 60 +/- 12% and phase III 58 +/- 14% (not significant). For controls, the incidences were 0%, 0%, and 1%, respectively (P < 0.006 versus Roux dogs). In the Roux limb, retrograde propagation of slow waves, and hence spike bursts, occurs even during aboral migration of phase III. This abnormality may contribute to the Roux Y stasis syndrome. PMID- 8508704 TI - Effects of prostaglandins on ornithine decarboxylase activity in rat small intestine. AB - Role of prostaglandins on feeding-associated induction of ornithine decarboxylase in small intestine was studied. Rats received intraperitoneal injection of either saline, or 16,16-dimethyl prostaglandin E2, or TRY-200 (a stable prostaglandin I2 analog), or refeeding, after a 44 hr-fast. Four hours later, mucosae from duodenum, jejunum, and ileum were scraped for subsequent measurements of enzyme activity of ornithine decarboxylase by a radiometric technique. Refeeding resulted in a profound induction of enzyme activity throughout the small intestine. Parenteral administration of prostaglandin I2 also led to a significant induction with the level similar to refeeding. The stimulatory effect of prostaglandin I2 was completely abolished by a specific and irreversible enzyme inhibitor, difluoromethylornithine. Prostaglandin E2 had a similar but lesser effect than prostaglandin I2 on the induction of the enzyme activity. Pretreatment with indomethacin, a cyclooxygenase inhibitor had no effect on feeding-associated enzyme induction. These results indicate that although exogenous prostaglandin I2 appears to be a potent stimulant for ornithine decarboxylase activity in rat small intestine, endogenous prostaglandins seem to play little or no role in feeding-associated induction of ornithine decarboxylase. PMID- 8508703 TI - Central and peripheral serotonergic influences on viscerovisceral inhibitory reflex during duodenal distension in sheep. AB - The effects of duodenal distension on forestomach and abomasal motility were investigated in conscious sheep chronically fitted with intraparietal electrodes, a duodenal cannula, and an intracerebroventricular cannula. Duodenal distensions with a balloon inflated with 40 ml (DD40) of water reduced the frequency of forestomach and abomasal contractions by 45 and 32%, respectively, while distension with 80 ml (DD80) induced a total inhibition. Methysergide, a mixed 5HT1-5HT2 antagonist administered intravenously (200 micrograms/kg) or intracerebroventricularly (20 micrograms/kg) suppressed the DD40-induced inhibition and reduced that induced by DD80. Spiroxatrine, a selective 5HT1A antagonist, intravenously (100 micrograms/kg) or intracerebroventricularly (10 micrograms/kg), suppressed the DD40 and DD80-induced inhibition, which was also attenuated by the 5HT2 antagonist ritanserin given intravenously (200 micrograms/kg) or intracerebroventricularly (20 micrograms/kg). Granisetron, a 5HT3 antagonist, injected intravenously (150 micrograms/kg), abolished the effects of DD40 and DD80 while it had no antagonistic action on DD40 and DD80 when given intracerebroventricularly (15 micrograms/kg). It is concluded that in sheep, duodenal distension inhibits forestomach and abomasal motility through 5HT1A and 5HT2 receptors at the level of the central nervous system and 5HT3 receptors located peripherally. PMID- 8508706 TI - Rat jejunal absorptive function after intestinal transplantation. Effects of extrinsic denervation. AB - Jejunal absorptive function was evaluated following small intestinal transplantation to determine the effects of extrinsic denervation. In particular, water and sodium absorption were measured following transplantation (denervated) and compared to a control group (Thiry-Vella). Water flow was initially secretory two days after transplantation (-41 +/- 27 microliters/min/g dry tissue weight) but became absorptive at day 8 (25 +/- 25). Water flow in the Thiry-Vella group was not significantly different (P > 0.05) from the transplant group at days 8 (17 +/- 7) and 10 (47 +/- 42). Sodium flows were also initially secretory in the transplant group and became absorptive. This study refutes previous claims that small bowel transplants have a deficiency of water absorption due to extrinsic denervation of the bowel and suggests normal absorptive function of water, electrolytes, and protein. PMID- 8508705 TI - Maturation of villus and crypt cell functions in rat small intestine. Role of dietary polyamines. AB - To evaluate the role of dietary polyamines in maturation of the rat small intestine, spermine was given orally twice daily to suckling pups from day 10 to day 14 postpartum at different doses: 0, 0.2, 0.5, 1, 2.5, and 5 mumol/dose. Compared to saline treated controls, spermine (5 mumol) produced significant increases in mucosal mass parameters (+12 to +57%, P < 0.05), induced prematurely an adult pattern of microvillous enzymes, and enhanced, respectively, by 19- and 3.5-fold (P < 0.01 vs controls) the concentration of the secretory component of p immunoglobulins in villous and crypt cells. The response of microvillous enzymes (lactase, sucrase, maltase, and aminopeptidase) to spermine was dose-dependent and -specific since oral administration of arginine (5 mumol) or ornithine (5 mumol) was without effect. Intestinal changes were found to be significant (P < 0.05) for doses of spermine exceeding 1 mumol/day, which is in the range of the amount of polyamines provided by solid pellets at weaning (0.4 mumol/g). However, intestinal changes were undetectable at the physiological amounts of polyamines consumed by pups from rat milk during the suckling period (less than 0.3 mumol/day). Consistent with a direct effect of spermine on the intestinal cell, the cytosolic activity of ornithine decarboxylase was depressed by 27-fold (P < 0.005 vs controls) in the jejunum, while inhibition of ornithine decarboxylase by alpha-difluoromethylornithine did markedly decrease but did not suppress the cell response to spermine. Alternately, plasma corticosteronemia, which was virtually absent by day 14 in controls, ranged between 1.4 and 4.6 micrograms/dl in 60% (N = 9) of the spermine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508708 TI - DNA-DNA hybridization demonstrates apparent genetic differences between Helicobacter pylori from patients with duodenal ulcer and asymptomatic gastritis. AB - We asked whether different clinical outcomes of Helicobacter pylori infection might be a reflection of genetic differences in infecting organisms. Using DNA DNA hybridization we examined whether hybridization levels grouped H. pylori isolates corresponding to the type of disease (gastric ulcer, duodenal ulcer, asymptomatic gastritis) from which they were recovered. Target DNAs were prepared from H. pylori strains cultured from gastric biopsy specimens of 25 patients; 5 with gastric ulcers, 9 with duodenal ulcers, and 11 from asymptomatic volunteers endoscopically proven not to have peptic ulcer disease. DNA-DNA hybridization was performed with whole genomic probes made from an isolate from each of the three disease categories. Using a DNA probe from an isolate from a duodenal ulcer patient, we found that isolates from patients with duodenal ulcer and nonulcer gastritis yielded significant differences in levels of hybridization. The levels of hybridization of DNA from H. pylori isolates from duodenal ulcer patients, gastric ulcer patients, and nonulcer gastritis controls were 85.5% +/- 7%, 83% +/ 3%, and 78.3% +/- 5%, respectively (mean +/- SD), and the difference between the hybridization levels obtained with duodenal ulcer and nonulcer control target DNAs was statistically significant (P = 0.025). These data suggest that the outcome of infection (eg, ulcer or no ulcer) may be due to virulence factors encoded by genomic DNA. If such differences exist, it should be possible to produce probes that would identify the ulcer virulence gene(s) and clearly distinguish between ulcerogenic and nonulcerogenic strains of H. pylori. PMID- 8508707 TI - Intestinal mucosal inflammation associated with human immunodeficiency virus infection. AB - The role of the human immunodeficiency virus type-1 (HIV) in producing intestinal disease was studied prospectively in 74 HIV-infected individuals with (43) or without (31) the acquired immunodeficiency syndrome (AIDS). Thirty-one subjects had enteric infections; all but one had AIDS. Alteration in bowel habits was the most common symptom and occurred independently of enteric infections. Abnormal histopathology was present in 69% of cases, and the finding was associated with altered bowel habits. An HIV-associated protein, p24, was detected in 71% of biopsies by ELISA assay. Tissue p24 contents varied with disease stage and were highest in HIV-infected individuals without AIDS (Walter Reed classes 3 and 4). Tissue p24 detection was associated with both altered bowel habits and histologic mucosal abnormalities. Tissue contents of the cytokines, tumor necrosis factor alpha and interleukin-1 beta, were higher in HIV-infected individuals than in controls and their elevations were independent of enteric infection. We conclude that HIV reactivation in the intestinal mucosa may be associated with an inflammatory bowel syndrome in the absence of other enteric pathogens. PMID- 8508709 TI - Prospective, randomized, investigator-blind trial of Helicobacter pylori infection treatment in patients with refractory duodenal ulcers. Healing and long term relapse rates. AB - In this study, 26 patients with duodenal ulcers refractory to treatment with H2 receptor antagonists for 8-12 weeks were randomly assigned to eight weeks of treatment with colloidal bismuth subcitrate (120 mg four times a day) alone (N = 12) or in combination with tetracycline hydrochloride (500 mg four times a day, days 0-14) and metronidazole (500 mg three times a day, days 15-28). Symptoms were scored and endoscopy, histology, and CLO tests were performed before, on completion of treatment, and 3, 6, 12, and 18 months after treatment. Treatment was considered successful when Helicobacter pylori was not detected by CLO tests and Warthin-Starry stains on gastric biopsies taken from antrum, body, and fundus. On triple therapy, ulcers healed in 12/14 patients (85.71%) and 10/14 (71.42%) patients became Helicobacter pylori-negative. On bismuth, only one patient became Helicobacter pylori-negative (8.33%, P < 0.0001), but ulcers healed in 8/12 patients (67%, P = NS). Six patients on bismuth, whose ulcers remained unhealed or relapsed early after healing, were offered triple therapy, which resulted in ulcer healing in three and Helicobacter pylori clearance in two patients. At 18 months, none of the Helicobacter pylori-negative patients had ulcer relapse. On the contrary, ulcers relapsed in all but one patient, who remained Helicobacter pylori-positive. Smoking and drinking did not influence the therapeutic outcome. The data confirm previous reports that many duodenal ulcers are infectious and therefore curable. PMID- 8508710 TI - Clinical patterns, natural history, and progression of ulcerative colitis. A long term follow-up of 1116 patients. AB - We studied the natural history of ulcerative colitis (UC) by following 1116 patients in whom UC had been diagnosed or confirmed at The Cleveland Clinic Foundation between 1960 and 1983. Data before 1973 were obtained retrospectively. Criteria for inclusion in the study were: a diagnosis of UC confirmed by clinical, radiographic, endoscopic, and histologic examination; disease location that could be defined as one of three categories (proctosigmoiditis, pancolitis, or left-sided colitis); and a follow-up of at least five years (mean = 12.7 years). Mean age at diagnosis was 32 years. Of the 1116 patients, 46.2% (516) had proctosigmoiditis; 36.7% (410) had pancolitis (colitis of the entire large intestine); and 17.0% (190) had left-sided colitis (from the dentate line to the splenic flexure). Early complications (within two years of diagnosis) included colonic hemorrhage (16.7%) and toxic colitis (12.7%). Complications were highest among patients with pancolitis. Surgery was required for 37.6% of the patients. Primary indications for surgery included chronic or intractable disability (40.2%), fulminating medical failure (16.9%), and colonic dilatation (18.4%). At the most recent follow-up, the disease had extended (progressed to a more serious category) in 53.8% of the patients, although 67.2% were asymptomatic and only 37.0% were on medications. Both the final disease destination and the initial diagnosis impacted cumulative colectomy-ileostomy rates. Factors associated with extension were toxic colitis (P < 0.0001); extent of disease at diagnosis (P < 0.0001); joint symptoms (P = 0.0008); younger age at diagnosis (P = 0.06); and severe bleeding (P = 0.07). PMID- 8508711 TI - Lymphocytic colitis. A definable clinical and histological diagnosis. AB - We reviewed colorectal biopsies and clinical records from 36 patients with chronic watery diarrhea who had been diagnosed as having microscopic colitis and compared their histologic features with the more detailed and precise criteria for lymphocytic colitis. Published pathologic criteria for lymphocytic colitis were applied to the biopsies and compared. Focal or diffuse nature of the lymphoid infiltrate were noted separately. The focal lymphoid infiltrate was related to lymphoid aggregates in the lamina propria of the mucosa. Eighteen cases had focal lymphoid cell infiltration, and 16 of them had associated diverticula, polyps, or both. Eighteen cases had diffuse lymphoid cell infiltration, and six of them had diverticula or polyps. Results indicate that focal cellular infiltration strongly predicts associated diverticula or polyps. The group with no diverticula or polyps most closely conformed to histologic criteria for lymphocytic colitis (Kruskal-Wallis P < 0.02). We conclude that lymphocytic colitis comprises a well-defined group of cases within the large and less-defined group of microscopic colitis. PMID- 8508712 TI - Splenic infarction associated with anticardiolipin antibodies in a patient with acquired immunodeficiency syndrome. AB - Although patients with AIDS frequently develop high titers of anticardiolipin antibodies, the clinical significance of this laboratory abnormality in AIDS patients is unknown. A 33-year-old female with AIDS, a prior small cerebrovascular accident, thrombocytopenia, and a coagulopathy suddenly developed left upper quadrant pain and tenderness due to splenic infarction associated with a high titer of anticardiolipin antibodies. Possible clinical manifestations of anticardiolipin antibodies in this patient include recurrent thromboembolism, coagulopathy, and thrombocytopenia. This case report suggests that anticardiolipin antibodies are associated with splenic infarction and that anticardiolipin antibodies associated with AIDS may sometimes be clinically significant. PMID- 8508714 TI - Perianal ulceration. A novel manifestation of angiocentric lymphoma. PMID- 8508713 TI - Massive hemobilia and acalculous cholecystitis due to benign gallbladder polyp. AB - A 37-year-old male with metachromatic leukodystrophy, a congenital cerebroside storage disease strongly associated with benign gallbladder polyps, presented with hemobilia and acalculous cholecystitis due to a long, slender, benign gallbladder polyp. This case report extends the clinical spectrum of gallbladder polyps and demonstrates a novel cause of hemobilia. The unusually long, slender polyp shape may have promoted hemorrhage due to the potential for torsion around a slender stalk. The mechanism of cholecystitis may have been cystic duct obstruction from blood clots or possibly from prolapse by the long, slender polyp into the cystic duct. PMID- 8508716 TI - Antiarrhythmic propafenone: improving patient outcomes. AB - Propafenone which is distributed as Rythmol by Knoll Pharmaceuticals (Whippany, New Jersey) is a class IC antiarrhythmic agent approved by the Food and Drug Administration (FDA) for the treatment of patients with life-threatening, malignant ventricular arrhythmias. It is still under investigation for use in patients with non-malignant ventricular arrhythmias, supraventricular arrhythmias, and atrial fibrillation or flutter. This author describes the pharmacokinetics and nurse's role for improving outcomes for patients on propafenone. PMID- 8508717 TI - Powerlessness and the pulmonary alveolar edema patient. AB - Everyone wants to maintain control over events in their life. The need for personal control does not end when the patient is hospitalized; instead the patient's need for personal control usually intensifies in critical care situations. The nursing diagnosis of powerlessness is common for most critical care patients, and especially so for the patient experiencing respiratory difficulties such as Pulmonary Alveolar Edema. These authors describe a model of powerlessness which suggests strategies for increasing the patient's control over his or her situation. PMID- 8508718 TI - Preventing complications in severe exfoliative skin diseases. AB - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome Type II are both exfoliative skin diseases with complications similar to burn patients. The critical care nurse's responsibility is to recognize the disease processes early and assure aggressive nursing care is provided to prevent the serious respiratory, gastrointestinal, sepsis, renal, and pain complications. PMID- 8508715 TI - Loperamide. Survey of studies on mechanism of its antidiarrheal activity. AB - In castor oil challenged rats, low doses of loperamide inhibit diarrhea and normalize intestinal propulsion. Unlike other opioids, loperamide is devoid of central opiate-like effects, including blockade of intestinal propulsion, up to the highest subtoxic oral dose. Nevertheless, the antidiarrheal action of loperamide can be considered to be mu-opiate receptor mediated, only a few in vitro effects at rather high concentrations being not naloxone-reversible. There is little evidence that interactions with intestinal opiate receptors directly change epithelial cell function. When secretory stimuli increase mucosal tension, however, loperamide may reverse the elevated hydrostatic tissue pressure that opposes normal absorption. This antisecretory effect at the mucosal level is accompanied by motor effects when loperamide reaches the myenteric mu-opiate receptors. At therapeutic doses for the treatment of acute diarrhea, it is likely that the mucosal effect prevails. PMID- 8508719 TI - Wealth and the right to refuse ICU discharge. Part 1: the ethical case. AB - When a patient cannot be helped significantly by further ICU care, can the family refuse discharge of the patient because they are able to pay for further care? Here is an actual case situation submitted from one of our readers, followed by the ethical case analysis and suggestions on what to do in a similar situation. PMID- 8508720 TI - Issues of transplantation: ethics of potential legislative changes. AB - Advances in transplantation technology and greater numbers of transplants have created an increasing disparity between the supply and the demand for organs. The new required-request legislation is only the beginning of legislation in this area. New legislation needs to increase the opportunity for donations without harming the rights of the patient. This author who has participated in the Surgeon General's Workshop on Organ Donation describes the issues involved in possible future legislation on organ and tissue donation. PMID- 8508721 TI - Increased intracellular calcium level in peripheral blood mononuclear cells of alcoholic patients under withdrawal. AB - Cytosolic free Ca2+ functions as a main regulator of numerous cellular processes, including those implicated in synthesis, release and responsiveness of hormones and neurotransmitters are discussed. To examine whether a change in the intracellular free calcium ion concentration [Ca2+]i occurs associated with delirium tremens and related states we compared [Ca2+]i in peripheral blood mononuclear cells (PBMC) of alcoholic patients under withdrawal with that of non alcoholic patients and of healthy controls. [Ca2+]i in PBMC of alcoholic patients was significantly higher (P < 0.001) compared to both control groups, suggesting that changes in [Ca2+]i may be relevant to increased excitability of the central nervous system. Increased [Ca2+]i in PBMC might be diagnostically valuable as a biological marker of alcohol dependency. PMID- 8508722 TI - Smoking and nicotine dependence in young adults: differences between blacks and whites. AB - Analysis of data from a household interview of young adults in Michigan was conducted to determine the prevalence of smoking and nicotine dependence and to examine the relationship of nicotine dependence with health indicators in black and white smokers. The NIMH Diagnostic Interview Schedule, revised to cover DSM III-R diagnoses, was used to assess nicotine dependence. A greater proportion of whites than blacks tried smoking, became regular smokers and met criteria for nicotine dependence. Whites had their first cigarette, began smoking regularly and manifested symptoms of nicotine dependence at a younger age than blacks. Nicotine dependence, rather than smoking per se, was associated with poor physical and psychological health among both blacks and whites. However, it had stronger associations with health problems in blacks than in whites. PMID- 8508723 TI - Substance use among resident doctors in Venezuela. AB - This study was aimed to develop a self-administered questionnaire to detect substance use disorders based on the Spanish version of the Diagnostic Interview Schedule (DIS) and to evaluate the frequency of substance abuse and/or dependence among resident physicians of a large university hospital in Venezuela. The questionnaire showed a high concordance with the clinical diagnoses. Frequency of substance abuse and dependence was evaluated among 191 resident doctors. The frequencies of lifetime diagnoses were: tobacco dependence: 20.9%; alcohol abuse: 11%; alcohol dependence: 0.5%; drug abuse: 1% and drug dependence: 1%; non pathological use of drugs: 20.4%. PMID- 8508724 TI - Relationship between intravenous use and achieving initial cocaine abstinence. AB - This study assessed whether route of cocaine administration (intravenous vs. intranasal) influences cocaine abstinence during the first 6 weeks of outpatient treatment. Fifty-nine persons received behavioral treatment or standard drug counselling in an outpatient clinic. Based on information collected at intake, intravenous users had fewer years of education, were employed in less skilled jobs, were less likely to be married, reported more negative consequences from cocaine use, reported using more cocaine per occasion and spent more money on cocaine per week than intranasal users. Intravenous and intranasal users did not differ significantly in the average duration of continuous cocaine abstinence (mean = 2.6 vs. mean = 3.3 weeks achieved during 6 weeks of treatment). The duration of abstinence between intravenous and intranasal users was equal in the behavioral treatment (mean = 4.2). In standard treatment the average duration was less among intravenous than intranasal users (mean = 0.9 vs. mean = 2.4), but that difference did not achieve statistical significance. Hepatitis and employment instability were associated with shorter periods of cocaine abstinence among intravenous users, whereas employment instability, lower job skill level, drug use severity and reports of memory loss were associated with shorter periods of cocaine abstinence among intranasal users. These results indicate that i.v. cocaine users can achieve a period of initial abstinence in an outpatient setting comparable to the duration of typical inpatient hospitalizations, although special types of outpatient treatment may be necessary to obtain a positive outcome. PMID- 8508725 TI - Orally self-administered cocaine in rhesus monkeys: transition from negative or neutral behavioral effects to positive reinforcing effects. AB - The establishment of orally delivered cocaine as a reinforcer was examined with nine rhesus monkeys. A 2% ethanol solution served as a reinforcer for all nine monkeys, for it maintained substantially higher response rates than did the concurrently available water vehicle. A test was initially conducted to determine whether cocaine would function as a reinforcer when substituted for 2% ethanol. When an intermediate cocaine concentration (0.2 mg/ml) was substituted for the ethanol solution, the drug maintained behavior at rates less than (seven monkeys), equal to (one monkey), or greater than (one monkey) those maintained by water. Thus, for eight of nine monkeys simple substitution of cocaine for ethanol was not sufficient to establish orally delivered cocaine as a reinforcer. In the next phase a stimulus-fading procedure was used. Blocks of training and testing sessions alternated. Across blocks of training sessions, increasing amounts of cocaine (0.0125, 0.025, 0.05, 0.1 mg/ml) were added to the 2% ethanol solution and subsequently the ethanol concentration was gradually decreased until only the 0.1 mg/ml cocaine solution remained; water was always concurrently available. Between each block of training sessions, a block of test sessions was inserted. Test sessions compared relative rates of responding maintained by two concurrently available drug solutions: (1) a solution containing the combination of ethanol and cocaine used in the prior training block and (2) a solution containing the same concentration of ethanol but with no cocaine. Thus, differences in rates of behavior maintained by the two solutions could be attributed to the presence of cocaine and the existence and degree of any such differences could be monitored at each step in the acquisition procedure. The outcome of the training procedure was that cocaine came to function as a reinforcer for six of the eight monkeys tested (the ninth monkey was not put through the fading procedure, having shown higher cocaine than vehicle rates during the initial substitution procedure). During the phase when ethanol was faded from the drug solution, differences between the combination cocaine-ethanol solution and the ethanol-only solution emerged: for the six monkeys that developed cocaine reinforced behavior, the combination solution maintained higher rates of responding than the ethanol solution alone. The opposite results were obtained with the remaining two monkeys. That cocaine had been established as a reinforcer was confirmed by persistent and orderly responding when dose and fixed ratio size were subsequently varied. PMID- 8508726 TI - Further neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholism. AB - D2 dopamine receptor function, as assessed by growth hormone (GH) responses to apomorphine (APO; 0.18-0.24 mg i.v.), was investigated in 15 male alcoholics with reported long-term abstinence. Results from only nine subjects could be evaluated. These subjects had been heavy alcohol consumers for a mean of 15 +/- 10 years and had thereafter been abstinent for a mean of 7 +/- 6 years prior to the investigation. Eight male healthy subjects, all of whom were light social drinkers, were selected as controls. The maximum GH responses to APO were significantly lower in the alcoholics (5.8 +/- 5.8 mU/l) than in the controls (22.1 +/- 19.2 mU/l). This finding gives neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholics with long-term abstinence. PMID- 8508727 TI - To drink or not to drink? Assessing conflicting desires in dependent drinkers in treatment. AB - Reactivity to Alcohol and Neutral Cues was compared in male, inpatient problem drinkers (N = 30). Subjects reported an overall desire not to drink alcohol which decreased in the presence of the Alcohol Cue. There were no cue-specific changes in heart rate, blood pressure and arousal level and a non-significant trend for increased stress in the Alcohol Cue condition. Subgroups of subjects reporting positive and negative desire for alcohol were identified. Subjects who reported negative desire for alcohol in the Alcohol Cue condition also reported greater self-efficacy to resist drinking in the future. These findings have implications for understanding the nature of self-reported desire for alcohol and its potential role in the treatment of alcohol dependence. PMID- 8508728 TI - Effect of colchicine on lactate production by isolated hepatocytes in rats treated with carbon tetrachloride and ethanol. AB - This study was designed to evaluate the lactate production by isolated hepatocytes in rats with cirrhosis induced by means CCl4 + ethanol and the effect of colchicine in this experimental model of fibrosis. The effect of colchicine on lactate metabolism may be important in explaining the beneficial mechanism of this therapy on liver cirrhosis. Colchicine treatment produced a decrease in perivenular fibrosis and a descense in the degrees of this histological lesion. Colchicine treatment ameliorated the subsequent further development of cirrhosis. Lactate production in colchicine groups were higher than the carbon tetrachloride groups. By contrast, a priori, we observed a decrease in lactacidaemia and a lesser lactate utilization in colchicine groups comparison with CCl4 + ethanol groups. Our results suggest that colchicine improves the fibrosis by a mechanism independent of hepatic lactate metabolism. PMID- 8508729 TI - The alcohol-deprivation effect in hybrid mice. AB - Hybrid mice (F1 CBA x C57Bl/6) after prolonged access to saccharin-menthol flavored 30% alcohol (FA) were deprived of it on two occasions, followed by test choices between (1) FA and water, and (2) FA and similarly flavored water. Although many mice failed to show deprivation-induced increases in FA intake, the mean rate of FA drinking during the first 1.5 h of renewed access was significantly increased even in the second test. Comparisons between the two tests suggest that flavor factors are generally less important than ethanol seeking behavior. PMID- 8508730 TI - Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans. AB - Intranasal cocaine (COC) and oral ethanol (ETOH) were administered to one group of seven research volunteers during daily experimental sessions. Following the determination of baseline subjective and performance measures, an ETOH cocktail (0, 19.4, 38.7 or 58.1 g of ETOH in lemonade) was consumed over a 10-min period. COC hydrochloride (4, 48, 96 mg) was inhaled 35-min after the start of ETOH drinking. In a separate experiment, seven research volunteers received intravenous cocaine and smoked marijuana (MJ), alone and in combination during daily experimental sessions. Following the determination of baseline measures, a 1-g MJ cigarette (0-2.7% delta 9-THC, w/w) was smoked and 13 min after the start of MJ smoking COC hydrochloride (0, 16, 32 mg) was given intravenously. ETOH increased simple-reaction time and decreased DSST trials. COC decreased DSST trials, increased incorrect responses on a list-learning task and attenuated the effect of ETOH on DSST performance. Only combinations of the high COC dose and the high MJ dose increased errors on a repeated acquisition task. Intranasal COC increased ratings of 'Stimulated,' and 'High' and LSD scores on the ARCI which were unaffected by ETOH. Increased ratings of 'Sedated' following ETOH alone were attenuated by intranasal (i.n.) COC. Intravenous COC and smoked MJ alone both increased ratings of 'Stimulated' and 'High.' There was a trend for combinations of i.v. COC and MJ to prolong these elevations. The results suggest that the interactive effects of COC in combination with ETOH or MJ, after acute administration, are subtle and in need of further analyses to better understand polydrug abuse. PMID- 8508731 TI - [Acute poisoning in patients of a medical intensive care unit]. AB - Data on 674 patients, admitted between 1986 and 1990 to a medical intensive care unit with acute poisoning (8.8% of total admissions), were analysed retrospectively. Females slightly predominated (53.4%); the age distribution peaked in the third decade of life. Attempted suicide made up 68.7 of all cases (64.8% in females), while 30% of intoxications were accidental (70.8% in males). Alcohol was the most common form of poison (41.4%), followed by benzodiazepines (27%) and psychoactive drugs (24.5%), more than one drug having been taken in 36.1% of cases. Artificial ventilation was needed in 14.2% of cases, while resuscitation was necessary in 1.6%. Forms of detoxication were: gastric lavage (58%), forced diuresis (6.4%), haemoperfusion (10.1%), haemodialysis (3.4%). An anticholinergic syndrome developed in 8% of cases, pneumonia in 3%, acute renal failure in 1.2%. Rhabdomyolysis occurred in 2.5%. The death rate was 1.2%. PMID- 8508732 TI - [Sudden cardiac death in childhood due to and abnormal origin of the coronary arteries]. AB - A seven-year-old girl suddenly collapsed during a sports session at school. An orthostatic syndrome was assumed. In the next two-and-a-half years she experienced four further attacks of weakness with vertigo and vomiting. Paediatric cardiological examination found her to be below the 3rd percentile for height, but the other physical findings and a thoracic radiogram were according to her age. The resting ECG showed increased T waves in V5 and V6, interpreted as signs of vagotonia. Echocardiography was normal, the results of the Schellong test suggested abnormal hypotonic circulatory regulation. Five months later the girl died suddenly after physical exertion. The post-mortem revealed anomalous origin of the left coronary artery (LCA) with a slit-like ostium from the right sinus of Valsalva. The very narrow initial part of the LCA passed tangentially through the wall of the aortic root and then took a leftward course between the aortic root and the pulmonary trunk.--It is assumed that the sudden cardiac death resulted from compression of the intramural segment of the LCA. PMID- 8508733 TI - [Therapy of pelvic floor insufficiency]. PMID- 8508734 TI - [Hematological significance of parvovirus B19 infection]. PMID- 8508735 TI - [Alcohol and coronary sclerosis]. PMID- 8508736 TI - [Nitrates in myocardial infarct]. PMID- 8508737 TI - [Therapeutic window following stenosis of the middle cerebral artery?]. PMID- 8508738 TI - [Intra-arterial calcium provocation test in the preoperative localization diagnosis of occult insulinoma]. PMID- 8508739 TI - [Intra-arterial calcium provocation test in the preoperative localization diagnosis of occult insulinoma]. PMID- 8508741 TI - Hyperkalaemic periodic paralysis: diagnosing the disease in the headlines. PMID- 8508740 TI - Stable dust--threshold limiting values, exposures variables and host risk factors. PMID- 8508742 TI - Ontogeny of gastric function vs the 'stress syndrome'. PMID- 8508743 TI - An important milestone in equine immunology: equine interleukin 2. PMID- 8508744 TI - Proceedings of the John P. Hughes International Workshop on Equine Endometritis. Davis, California, August 1992. PMID- 8508745 TI - Effect of stabling on bronchoalveolar cells obtained from normal and COPD horses. AB - Bronchoalveolar lavages (BAL) were performed before and after 3 weeks of housing in 5 horses suffering from COPD and 5 normal horses. In the two groups, the total number of cells recovered remained unchanged after stabling. The most common cell populations in BAL fluid of control animals were alveolar macrophages (46.4%) and lymphocytes (44.9%). The percentage of neutrophils increased after stabling from 8.7% to 27.6%. In COPD horses, lymphocytes predominated (40.7%) in animals at pasture with neutrophils increasing from 29.4% to 71.6% after stabling. After fractionation by Percoll density gradient, alveolar macrophages and neutrophils from normal and COPD horses had a similar density distribution. After stabling, these cells from normal horses were increased in the low density layers, while those from COPD horses were predominantly in the hyperdense layers. Therefore, BAL cells obtained from COPD animals at pasture and after stabling differ from those of control horses in the same environment, not only in their populations but also in their buoyant densities. These differences could be related to different states of cellular activation and perhaps be responsible for disease activity in the COPD horses. PMID- 8508746 TI - Treatment of respiratory infections in horses with ceftiofur sodium. PMID- 8508747 TI - Racing performance of standardbreds after conservative and surgical treatment for tarsocrural osteochondrosis. AB - A retrospective study of 114 Standardbred horses diagnosed with osteochondrosis (OC) of the cranial intermediate ridge of the distal tibia was carried out, and their subsequent race records were compared with 456 control horses. Each OC affected horse was compared with 4 horses randomly selected from a list of horses matched to it by year of birth, sex and sire. The horses with OC were treated by arthroscopic removal of osteochondral fragments (N = 58) or managed conservatively (N = 56). The clinical presentation of these two groups was similar, although joint effusion was a more common presenting sign in the group that received surgical treatment. There was no association between presence of lameness and the type of treatment used. Data from the race records of treated and control horses (including the number of starts, lifetime earnings and record racing times) were compared. Overall, horses treated for OC had significantly fewer starts than, but earnings similar to, those in the control group. However, when stratification by sex was performed, females with OC made fewer starts and had lower earnings than did their control group. There was no significant difference in record time between OC-affected horses and controls. These results indicate that horses treated for osteochondrosis of the cranial intermediate ridge of the distal tibia performed as well as matched controls. PMID- 8508748 TI - Assessment and treatment of equine humeral fractures: retrospective study of 54 cases (1972-1990). AB - Fractures of the humerus were diagnosed in horses at The Ohio State University Veterinary Teaching Hospital. Twenty-four horses (44.4%) were destroyed after radiographic assessment (mean age of 5.0 years). Surgical treatment was elected in 13 horses (24.1%, mean age of 0.42 years). Conservative management, consisting of prolonged stall rest, was chosen for 17 horses (31.5%, mean age of 2.2 years). In the surgically treated group, 3 foals (23.1%) all less than 2 months of age at the time of fracture and treated with intramedullary stack pinning, survived and became athletically sound. After conservative treatment, 9 (52.9%) horses were considered successful, 4 becoming athletically sound and 5 becoming pasture sound. The mean age at the time of presentation in the 9 horses considered successful was 1.81 years. With current fixation techniques, conservative management of equine humeral fractures appears to be as good an option as surgical treatment. PMID- 8508749 TI - Airborne dust and aeroallergen concentration in a horse stable under two different management systems. AB - Airborne dust concentration (ADC) was measured in 2 different horse management systems using an Andersen cascade impactor in the box-stall, and a personal Marple cascade impactor attached to the halter to measure ADC in the breathing zone. The levels of aeroallergens implicated in chronic obstructive pulmonary disease were measured by radioallergosorbent-inhibition immunoassay. A conventional management system (System C) utilising hay feed and straw bedding, and a recommended environment (System R) utilising wood shaving bedding and a complete pelleted diet were studied. In the stall, total and respirable ADC (geometric mean) were significantly higher in System C (2.55 mg/m3; 0.44 mg/m3, respectively) than in System R (0.70 mg/m3; 0.20 mg/m3, respectively). In System C, the total and respirable ADC in the breathing zone (17.51 mg/m3; 9.28 mg/m3) were much higher than in the stall, but values in both regions were similar in System R (0.52 mg/m3; 0.30 mg/m3). Major aeroallergens were significantly higher in System C than in System R: Micropolyspora faeni (1423 ng/m3 and 705 ng/m3), Aspergillus fumigatus (1823 ng/m3 and 748 ng/m3), and mite allergens (1420 ng/m3 and 761 ng/m3). Measurement of ADC with personal samplers indicates that the very high inhalation challenge in the breathing zone is not reflected in measurements of stall air quality. When compared with System C, System R produced only 3% of the respirable dust burden in the breathing zone and a decreased aeroallergen challenge. PMID- 8508750 TI - A prospective study of septicaemia in colostrum-deprived foals. AB - Fourteen mares and their foals were attended at parturition. After mare-foal bonding, 8 colostrum-deprived (CD) foals were removed from their dams, deprived of colostrum, and provided with an alternative milk source for the first 24 h of life. The mares were milked out every 2-4 h during this period to remove colostrum, after which the CD foals were returned to their mares and allowed to nurse. Six colostrum-fed (CF) foals were allowed to suck colostrum in the normal manner. Foal serum IgG concentration was determined by single radial immunodiffusion (means, CD = 0 mg/dl; CF = 1,508 mg/dl). Accepted methods were used to minimise infections in the neonatal foals. Of the 8 CD foals, 7 demonstrated clinical signs of sepsis. Septicaemia was confirmed in 5 of the 7 septicaemic CD foals by ante-mortem blood culture or by culture of tissue at necropsy. Organisms isolated included: Actinobacillus equuli, Escherichia coli, undifferentiated coliforms, Pseudomonas spp., and Actinomyces pyogenes. Clinically ill foals were treated with antimicrobial drugs, intravenous fluid therapy, flunixin meglumine, and anti-endotoxin hyperimmune serum. Three septicaemic CD foals survived. Four of 7 septicaemic CD foals died or were destroyed. Post-mortem lesions included bacterial embolic pneumonia, glomerulonephritis/nephritis, lymphoid depletion/atrophy, splenic and lymphoid necrosis, hepatitis, septic arthritis, and systemic bacterial embolism. None of the CF foals became septicaemic. One CF foal had foal heat diarrhoea and 1 CF foal had a serum IgG concentration of 160 mg/dl (i.e. failure of passive transfer), but both foals were otherwise normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508751 TI - Clinical and pathological features of thoracic neoplasia in the horse. AB - Thirty-eight horses with confirmed thoracic neoplasia included 28 (37.7%) with lymphosarcoma, 4 (10.5%) with metastatic renal cell carcinoma, 2 (5.3%) with primary lung carcinoma, 2 (5.3%) with secondary squamous cell carcinoma from the stomach, 1 (2.6%) with pleural mesothelioma, and 1 (2.6%) with malignant melanoma. The major clinical features included weight loss, inappetence, dyspnoea and coughing, but in cases of lung metastases, they related more to the primary site of tumour formation. Haematological and serum biochemical abnormalities were non-specific. Specific pre-mortem diagnosis was made in 14 horses; this was most readily achieved when exfoliated neoplastic cells were present in pleural fluid. PMID- 8508752 TI - Are tapeworms associated with equine colic? A case control study. AB - Faeces samples from 116 horses with colic and 115 non-colic cases were assayed by a centrifugation/floatation method for the presence of tapeworm eggs. Analysis of these data failed to demonstrate an association between tapeworm infection and colic of all types. The data were further analysed according to anatomical site of the lesion causing colic. The risk of ileocaecal colic was increased in the presence of tapeworms. Age, breed and sex were evaluated as possible confounding factors but had no association with the incidence of colic. This study suggests an association between tapeworms and colic of ileocaecal origin. PMID- 8508753 TI - Clinical syndrome and diagnosis of hyperkalaemic periodic paralysis in quarter horses. AB - Of the 16 horses studied, 14 belonged to a family previously shown to be susceptible to hyperkalaemic periodic paralysis (HPP), and 8 were shown to have HPP. Diagnosis of HPP by electromyographic detection of myotonic discharges or by oral administration of KCl to induce clinical signs and hyperkalaemia had similar reliability and gave the same result in 80% of cases. KCl had to be administered at doses up to 0.2 g/kg bodyweight to produce signs in some horses. KCl challenge testing was more time consuming than EMG and resulted in one fatality. Overall, electromyography and potassium challenge testing together gave the most accurate diagnosis. Horses were more likely to manifest signs of HPP if they were immature. There was no sex predisposition. The most frequent sign of HPP was muscle fasciculation. Other signs were sweating, muscle spasm, and weakness. Respiratory rate increased greatly during some attacks. Attacks of muscle fasciculation without hyperkalaemia were observed in 2 HPP-affected horses. Affected horses had a greater frequency of spontaneous clinical abnormalities, due mainly to trailering problems, traumatic abrasions and episodes of continuous muscle fasciculation. Hyperkalaemia was confirmed in only one of these instances. PMID- 8508754 TI - Plasma constituents during incremental treadmill exercise in intact and splenectomised horses. AB - Six intact and 6 splenectomised mares were given an incremental exercise test on a treadmill to examine the fluid and electrolyte changes associated with exercise and the role of the spleen in these changes. Blood samples were obtained at rest and at the end of each 1-min step of the test. Exercise at 7 m/sec caused significant (P < 0.05) increases in plasma osmolality (intact, +9.9%; splenectomised, +6.2%), plasma protein concentration (intact, +15.8%; splenectomised, +11.4%), and plasma K+ concentration (intact 46%; splenectomised, +57%). Plasma Na+ concentration did not increase significantly (P > 0.05) in either group (intact = 2.7%; splenectomised, = 3.5%). This appears to be the first record of substantial changes of these constituents during short-term exercise, even before the onset of visible sweat losses. The changes in the concentration of plasma protein suggest that short-term exercise causes a decrease in plasma volume. The changes in the concentration and content of sodium suggest that this is an isotonic shift of fluid. The increase in plasma potassium concentration appears to be due to haemoconcentration as well as an increase in the content of potassium within the vascular compartment. PMID- 8508755 TI - A comparison of endometrial biopsy, culture and cytology during oestrus and dioestrus in the horse. PMID- 8508756 TI - cDNA cloning of equine interleukin-2 by polymerase chain reaction. PMID- 8508757 TI - Pulmonary granular cell tumour in 2 horses. PMID- 8508758 TI - Implantation of a programmable atrioventricular pacemaker in a donkey with complete atrioventricular block and syncope. PMID- 8508759 TI - Dynamic collapse of the roof of the nasopharynx as a cause of poor performance in a standardbred colt. PMID- 8508760 TI - Two-dimensional structure of the membrane domain of human band 3, the anion transport protein of the erythrocyte membrane. AB - The membrane domain of human erythrocyte Band 3 protein (M(r) 52,000) was reconstituted with lipids into two-dimensional crystals in the form of sheets or tubes. Crystalline sheets were monolayers with six-fold symmetry (layer group p6, a = b = 170 A, gamma = 60 degrees), whereas the symmetry of the tubular crystals was p2 (a = 104 A, b = 63 A, gamma = 104 degrees). Electron image analysis of negatively stained specimens yielded projection maps of the protein at 20 A resolution. Maps derived from both crystal forms show that the membrane domain is a dimer of two monomers related by two-fold symmetry, with each monomer consisting of three subdomains. In the dimer, two subdomains of each monomer form a roughly rectangular core (40 x 50 A in projection), surrounding a central depression. The third subdomain of the monomer measures approximately 15 x 25 A in projection and appears to be connected to the other two by a flexible link. We propose that the central depression may represent the channel for anion transport while the third subdomain appears not to be directly involved in channel formation. PMID- 8508761 TI - The vacuolar membrane protein gamma-TIP creates water specific channels in Xenopus oocytes. AB - The vacuolar membrane (tonoplast) of higher plant cells contains an abundant 27 kDa protein called TIP (tonoplast intrinsic protein) that occurs in different isoforms and belongs to a large family of homologous channel-like proteins found in bacteria, plants and animals. In the present study, we identified and characterized the function of gamma-TIP from Arabidopsis thaliana by expression of the protein in Xenopus oocytes. gamma-TIP increased the osmotic water permeability of oocytes 6- to 8-fold, to values in the range 1-1.5 x 10(-2) cm/s. Similar results were obtained with the homologous human erythrocyte protein CHIP28, recently identified as the erythrocyte water channel. The bacterial homolog GlpF did not affect the osmotic water permeability of oocytes, but facilitated glycerol uptake, in accordance with its known function. By contrast, gamma-TIP did not promote glycerol permeability. Voltage clamp experiments provided evidence showing that gamma-TIP induced no electrogenic ion transport in oocytes, especially during osmotic challenge that resulted in massive transport of water. These results allow us to conclude that the various protein members of the MIP family have unique and specific transport functions and that the plant protein gamma-TIP likely functions as a water specific channel in the vacuolar membrane. PMID- 8508762 TI - Protocadherins: a large family of cadherin-related molecules in central nervous system. AB - Using the polymerase chain reaction, we have isolated numerous rat and human cDNAs of which the deduced amino acid sequences are highly homologous to the sequences of the extracellular domain of cadherins. The entire putative coding sequences for two human proteins defined by two of these cDNAs have been determined. The overall structure of these molecules is very similar to that of classic cadherins, but they have some unique features. The extracellular domains are composed of six or seven subdomains that are very similar to those of cadherins, but have characteristic properties. The cytoplasmic domains, on the other hand, have no significant homology with those of classic cadherins. Since various cDNAs with almost identical features were obtained also from Xenopus, Drosophila and Caenorhabditis elegans, it appears that similar molecules are expressed in a variety of organisms. We have tentatively named these proteins protocadherins. They are highly expressed in brain and their expression appears to be developmentally regulated. The proteins expressed from the two full-length cDNAs in L cells were approximately 170 or 150 kDa in size, and were localized mainly at cell-cell contact sites. Moreover, the transfectants showed cell adhesion activity. PMID- 8508763 TI - An extended surface of binding to Trk tyrosine kinase receptors in NGF and BDNF allows the engineering of a multifunctional pan-neurotrophin. AB - Neurotrophin-mediated cell survival and differentiation of vertebrate neurons is caused by ligand-specific binding to the Trk family of tyrosine kinase receptors. However, sites in the neurotrophins responsible for the binding to Trk receptors and the mechanisms whereby this interaction results in receptor activation and biological activity are unknown. Here we show that in nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), discontinuous stretches of amino acid residues group together on one side of the neurotrophin dimer forming a continuous surface responsible for binding to and activation of TrkA and TrkB receptors. Two symmetrical surfaces are formed along the two-fold axis of the neurotrophin dimer providing a model for ligand-mediated receptor dimerization. Mutated neurotrophins inducing similar levels of receptor phosphorylation showed different biological activities, suggesting that structural differences in a ligand may result in dissimilar responses in a given tyrosine kinase receptor. Our results allowed us to combine structural elements from NGF, BDNF and neurotrophin-3 to engineer a pan-neurotrophin that efficiently activates all Trk receptors and displays multiple neurotrophic specificities. PMID- 8508764 TI - Targeting of cytochrome b2 into the mitochondrial intermembrane space: specific recognition of the sorting signal. AB - Cytochrome b2 contains 2-fold targeting information: an amino-terminal signal for targeting to the mitochondrial matrix, followed by a second cleavable sorting signal that functions in directing the precursor into the mitochondrial intermembrane space. The role of the second sorting sequence was analyzed by replacing one, two or all of the three positively charged amino acid residues which are present at the amino-terminal side of the hydrophobic core by uncharged residues or an acidic residue. With a number of these mutant precursor proteins, processing to the mature form was reduced or completely abolished and at the same time targeting to the matrix space occurred. The accumulation in the matrix depended on a high level of intramitochondrial ATP. At low levels of matrix ATP, the mutant proteins were sorted into the intermembrane space like the wild-type precursors. THE RESULTS: (i) suggest the existence of one or more matrix components that specifically recognize the second sorting signal and thereby trigger the translocation into the intermembrane space; (ii) indicate that the mutant signals have reduced ability to interact with the recognition component(s) and then embark on the default pathway into the matrix by interacting with mitochondrial hsp70 in conjunction with matrix ATP; (iii) strongly argue against a mechanism by which the hydrophobic segment of the sorting sequence stops translocation in the hydrophobic phase of the inner membrane. PMID- 8508765 TI - V(D)J recombination in B cells is impaired but not blocked by targeted deletion of the immunoglobulin heavy chain intron enhancer. AB - We have assessed the importance of the immunoglobulin heavy chain (IgH) intron enhancer for recombination of variable gene segments (V, D and J) during B cell development. We generated chimeric mice with embryonic stem cells lacking the intron enhancer from one of their IgH loci. The IgH intron enhancer was substituted by a short oligonucleotide through homologous recombination using the 'Hit and Run' procedure. V(D)J recombination occurred less frequently on mutant alleles, but was not blocked completely. Quantitative polymerase chain reaction analyses demonstrated that 15-30% of the mutated loci in mature B cells were unrearranged, in striking contrast to the wild-type alleles. The remainder of the mutated loci underwent D-J (65-80%) as well as V-DJ rearrangements, although the latter were less frequent (3-6%). These results are in line with previous data which showed that the V(D)J recombination machinery is modulated through cis regulatory elements within the intron enhancer. However, our data predict the existence of additional cis-regulatory element(s) which, together with the intron enhancer, are required to activate the V(D)J recombination machinery fully. Such cis-regulatory element(s) might function as an enhancer of recombination or as a locus control region regulating the accessibility of the IgH locus. PMID- 8508766 TI - Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans. AB - Immunoglobulins (Ig) secreted from a plasma cell contain either kappa or lambda light chains, but not both. This phenomenon is termed isotypic kappa-lambda exclusion. While kappa-producing cells have their lambda chain genes in germline configuration, in most lambda-producing cells the kappa chain genes are either non-productively rearranged or deleted. To investigate the molecular mechanism for isotypic kappa-lambda exclusion, in particular the role of the Ig kappa intron enhancer, we replaced this enhancer by a neomycin resistance (neoR) gene in embryonic stem (ES) cells. B cells heterozygous for the mutation undergo V kappa-J kappa recombination exclusively in the intact Ig kappa locus but not in the mutated Ig kappa locus. Homozygous mutant mice exhibited no rearrangements in their Ig kappa loci. However, splenic B cell numbers were only slightly reduced as compared with the wild-type, and all B cells expressed lambda chain bearing surface Ig. These findings demonstrate that rearrangement in the Ig kappa locus is not essential for lambda gene rearrangement. We also generated homozygous mutant mice in which the neoR gene was inserted at the 3' end of the Ig kappa intron enhancer. Unexpectedly, mere insertion of the neoR gene showed some suppressive effect on V kappa-J kappa recombination. However, the much more pronounced inhibition of V kappa-J kappa recombination by the replacement of the Ig kappa intron enhancer suggests that this enhancer is essential for V kappa-J kappa recombination. PMID- 8508767 TI - The Drosophila neuralized gene encodes a C3HC4 zinc finger. AB - The neurogenic genes of Drosophila are required for cell-cell communication that determines the choice between neuronal and epidermal cell fate. Here we report the molecular characterization of the neurogenic gene neuralized (neu) and show that it encodes a protein containing a C3HC4 zinc finger DNA-binding motif. This motif has been previously characterized in a variety of regulatory proteins, including transcription factors, locus-specific Drosophila chromosomal proteins, and oncoproteins. These results suggest a nuclear function for neu in the cell cell signalling process responsible for inhibiting neuronal determination. PMID- 8508768 TI - GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain. AB - In Saccharomyces cerevisiae, efficient expression of glycolytic and translational component genes requires two DNA binding proteins, RAP1 (which binds to UASRPG) and GCR1 (which binds to the CT box). We generated deletions in GCR1 to test the validity of several different models for GCR1 function. We report here that the C terminal half of GCR1, which includes the domain required for DNA binding to the CT box in vitro, can be removed without affecting GCR1-dependent transcription of either the glycolytic gene ADH1 or the translational component genes TEF1 and TEF2. We have also identified an activation domain within a segment of the GCR1 protein (the N-terminal third) that is essential for in vivo function. RAP1 and GCR1 can be co-immunoprecipitated from whole cell extracts, suggesting that they form a complex in vivo. The data are most consistent with a model in which GCR1 is attracted to DNA through contact with RAP1. PMID- 8508769 TI - The Aspergillus nidulans brlA regulatory locus consists of overlapping transcription units that are individually required for conidiophore development. AB - The Aspergillus nidulans brlA locus controls conidiophore development in conjunction with the products of several other regulatory loci. In this paper, we show that the brlA locus consists of overlapping transcription units, designated alpha and beta, with alpha transcription initiating within beta intronic sequences. The predicted BrlA polypeptides differ by 23 amino acid residues at their N-termini. Targeted mutations specifically eliminating either the alpha or beta transcript led to developmental abnormalities similar to those produced by previously identified hypomorphic mutants, showing that both transcripts have essential functions for normal development. However, provision of additional doses of alpha in a beta- strain or of beta in an alpha- strain remediated the developmental defects, indicating that the polypeptides have redundant functions. It is likely that differential regulation of alpha and beta expression in the wild type is important for the initiation and temporal regulation of development. PMID- 8508770 TI - Translational repression of brlA expression prevents premature development in Aspergillus. AB - The Aspergillus nidulans brlA developmental regulatory locus consists of two overlapping transcription units, brlA alpha and brlA beta, which encode functionally related polypeptides. We used translational fusions between each of the predicted brlA reading frames and the Escherichia coli lacZ gene to test the hypothesis that developmental regulation of brlA alpha and brlA beta expression occurs through different mechanisms. brlA alpha is transcriptionally controlled and a large portion of brlA alpha-directed beta-galactosidase activity is regulated in a brlA-dependent manner. In contrast, brlA beta mRNA is constitutively transcribed but translation of the brlA polypeptide is prevented by the presence of a short open reading frame (microORF) present in the 5' end of brlA beta mRNA. Removing the microORF initiation codon leads to deregulated brlA expression, resulting in an inappropriate activation of development. We propose that one mechanism for developmental induction in A.nidulans involves translational control. PMID- 8508771 TI - Activation of the prespore and spore cell pathway of Dictyostelium differentiation by cAMP-dependent protein kinase and evidence for its upstream regulation by ammonia. AB - Expression of a dominant inhibitor of the Dictyostelium cAMP-dependent protein kinase in prespore cells blocks their differentiation into spore cells. The resultant structures comprise a normal stalk supporting a bolus of cells that fail to express a sporulation-specific gene and that show greatly reduced levels of expression of several prespore-specific genes. The latter result suggests that in addition to activating spore formation, the cAMP-dependent protein kinase may play a role in initial prespore cell differentiation. Development of the strain expressing the dominant inhibitor is hypersensitive to the inhibitory effects of ammonia, the molecule that is believed to repress entry into culmination during normal development. This result supports a model whereby a decrease in ambient ammonia concentration at culmination acts to elevate intracellular cAMP and hence induce terminal differentiation. PMID- 8508772 TI - A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora. AB - Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions. PMID- 8508773 TI - The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa. AB - Erwinia carotovora and Pseudomonas aeruginosa secrete exoenzymes that contribute to the pathogenesis of plant and mammalian infections respectively. E.carotovora mutants defective in synthesis of the pectinase, cellulase and protease exoenzymes were isolated and classified into two groups. Group 2 mutants were found to be defective in the production of a small freely diffusible molecule, N 3-(oxohexanoyl)-L-homoserine, lactone (HSL), and were avirulent. Addition of exogenous HSL to these group 2 mutants restores synthesis of the exoenzymes and virulence in planta. Of the exoenzymes of P.aeruginosa the metalloprotease, elastase, is an established virulence determinant. Mutants of P.aeruginosa that are defective in elastase production have been isolated and were again found to fall into two groups. Analogous to the group 2 mutants of E.carotovora, group 2 mutants of P. aeruginosa are defective in the synthesis of HSL and exogenous HSL restores elastase production. HSL has now been linked to the control of bioluminescence in Vibrio fischeri, carbapenem antibiotic production of E.carotovora and the above exoenzyme virulence determinants. This information significantly enhances our understanding of the extent and nature of pheromone mediated gene expression control in prokaryotes. PMID- 8508774 TI - Lrp, a major regulatory protein in Escherichia coli, bends DNA and can organize the assembly of a higher-order nucleoprotein structure. AB - Lrp (Leucine-responsive regulatory protein) is a global regulatory protein that controls the expression of many operons in Escherichia coli. One of those operons, ilvIH, contains six Lrp binding sites located within a several hundred base pair region upstream of the promoter region. Analysis of the binding of Lrp to a set of circularly permuted DNA fragments from this region indicates that Lrp induces DNA bending. The results of DNase I footprinting experiments suggest that Lrp binding to this region facilitates the formation of a higher-order nucleoprotein structure. To define more precisely the degree of bending associated with Lrp binding, one or two binding sites were separately cloned into a pBend vector and analyzed. Lrp induced a bend of approximately 52 degrees upon binding to a single binding site, and the angle of bending is increased to at least 135 degrees when Lrp binds to two adjacent sites. Lrp-induced DNA bending, and a natural sequence-directed bend that exists within ilvIH DNA, may be architectural elements that facilitate the assembly of a nucleoprotein complex. PMID- 8508775 TI - DNA looping and the helical repeat in vitro and in vivo: effect of HU protein and enhancer location on Hin invertasome assembly. AB - Site-specific DNA inversion by the Hin recombinase requires the formation of a multicomponent nucleo-protein structure called an invertasome. In this structure, the two recombination sites bound by Hin are assembled together at the Fis-bound recombinational enhancer with the requisite looping of the intervening DNA segments. We have analyzed the role of the HU protein in invertasome assembly when the enhancer is located at variable positions close to one of the recombination sites. In the absence of HU in vitro and in hupA hupB mutant cells in vivo, invertasome assembly is very inefficient when there is < 104 bp of DNA between the enhancer and recombination site. Invertasome assembly in the presence of HU in vitro or in vivo displayed a periodicity beginning with 60 bp of intervening DNA that reflected its helical repeat. The average helical repeat for this DNA region was calculated by autocorrelation and Fourier transformation to be 11.2 bp per turn for supercoiled DNA both in the presence of HU in vitro and in hup+ cells in vivo. HU is the only protein in Escherichia coli that can promote invertasome formation with short DNA lengths between the enhancer and recombination sites. However, the presence of certain polyamines and a protein activity present in HeLa nuclear extracts can efficiently substitute for HU in invertasome assembly. These data support a model in which HU binds non specifically to the DNA between the enhancer and recombination site to facilitate DNA looping. PMID- 8508776 TI - Autonomously replicating single-copy episomes in Trypanosoma brucei show unusual stability. AB - We have obtained several autonomously replicating plasmids in procyclic Trypanosoma brucei. Two of these have been analyzed in detail. Both exist as monomeric single-copy episomes, which nevertheless demonstrate significant stability. These episomes transform procyclics at frequencies that are at least 60-fold higher than those achieved earlier with non-replicating molecules. A modified version of one of these episomes is able to replicate autonomously in bloodstream form T. brucei but it is unstable in this developmental stage of the organism. These episomes will prove useful as shuttle vectors, in functional complementation studies, in the construction of promoter-traps for the isolation of transcriptional promoters in T. brucei, and importantly, as models for the analysis of DNA replication in this ancient eukaryotic lineage. PMID- 8508777 TI - Poly(A) signals and transcriptional pause sites combine to prevent interference between RNA polymerase II promoters. AB - Transcriptional termination by RNA polymerase II at the 3' end of genes encoding poly(A)+ mRNAs is thought to require two distinct cis-active elements: a functional poly(A) signal and a downstream transcriptional pause site. An important requirement for efficient termination is to prevent transcriptional interference of downstream-located promoters. We have therefore investigated whether these two elements, individually or in combination, can prevent transcriptional interference of RNA polymerase II-activated promoters. For this purpose, we constructed an expression plasmid containing two tandem retroviral long terminal repeats (LTRs) derived from HIV-1. When transfected into HeLa cells, this construct resulted in transcriptional interference of the LTR promoters. Using this assay, we were able to show that a single poly(A) signal was able to protect an otherwise occluded promoter. This effect depended on the RNA-processing strength of the poly(A) signal. Furthermore, transcriptional pause sites provided adequate protection against promoter occlusion even when tested alone. Finally, a combined element consisting of a poly(A) signal followed by a pause site was more efficient in promoter protection than either element on its own. These results indicate that an interference-blocking element can take various forms: a poly(A) signal, a transcriptional pause site or a combination of both. PMID- 8508778 TI - A U3 snoRNP protein with homology to splicing factor PRP4 and G beta domains is required for ribosomal RNA processing. AB - Yeast fibrillarin (NOP1) is an evolutionarily conserved, nucleolar protein necessary for multiple steps in ribosome biogenesis. Yeast mutants lacking a functional NOP1 gene can be complemented by human fibrillarin but are temperature sensitive for growth and impaired in pre-rRNA processing. In order to identify components which interact functionally with human fibrillarin in yeast, we isolated extragenic suppressors of this phenotype. One dominant suppressor, sof1 56, which is allele-specific for human fibrillarin and restores growth and pre RNA processing at 35 degrees C, was cloned by in vivo complementation. The wild type allele of SOF1 is essential for cell growth and encodes a novel 56 kDa protein. In its central domain, SOF1 contains a repeated sequence also found in beta-subunits of trimeric G-proteins and the splicing factor PRP4. A single amino acid exchange in the G beta-like repeat domain is responsible for the suppressing activity of sof1-56. Indirect immunofluorescence shows that SOF1 is located within the yeast nucleolus. Co-immunoprecipitation demonstrates the physical association of SOF1 with U3 small nucleolar RNA and NOP1. In vivo depletion of SOF1 leads to impaired pre-rRNA processing and inhibition of 18S rRNA production. Thus, SOF1 is a new component of the nucleolar rRNA processing machinery. PMID- 8508779 TI - Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. AB - In vitro selection experiments have been used to isolate active variants of the 50 nt hairpin catalytic RNA motif following randomization of individual ribozyme domains and intensive mutagenesis of the ribozyme-substrate complex. Active and inactive variants were characterized by sequencing, analysis of RNA cleavage activity in cis and in trans, and by substrate binding studies. Results precisely define base-pairing requirements for ribozyme helices 3 and 4, and identify eight essential nucleotides (G8, A9, A10, G21, A22, A23, A24 and C25) within the catalytic core of the ribozyme. Activity and substrate binding assays show that point mutations at these eight sites eliminate cleavage activity but do not significantly decrease substrate binding, demonstrating that these bases contribute to catalytic function. The mutation U39C has been isolated from different selection experiments as a second-site suppressor of the down mutants G21U and A43G. Assays of the U39C mutation in the wild-type ribozyme and in a variety of mutant backgrounds show that this variant is a general up mutation. Results from selection experiments involving populations totaling more than 10(10) variants are summarized, and consensus sequences including 16 essential nucleotides and a secondary structure model of four short helices, encompassing 18 bp for the ribozyme-substrate complex are derived. PMID- 8508780 TI - Protein splicing of the yeast TFP1 intervening protein sequence: a model for self excision. AB - Protein splicing is the protein analogue of RNA splicing in which the central portion (spacer) of a protein precursor is excised and the amino- and carboxy terminal portions of the precursor reconnected. The yeast Tfp1 protein undergoes a rapid protein splicing reaction to yield a spliced 69 kDa polypeptide and an excised 50 kDa spacer protein. We have demonstrated that the 69 kDa species arises by reformation of a bona fide peptide bond. Deletion analyses indicate that only sequences in the central spacer protein of the Tfp1 precursor are critical for the protein splicing reaction. A fusion protein in which only the Tfp1 spacer domain was inserted into an unrelated protein also underwent efficient splicing, demonstrating that all of the information required for protein splicing resides within the spacer domain. Alteration of Tfp1p splice junction residues blocked or kinetically impaired protein splicing. A protein splicing model is presented in which asparagine rearrangement initiates the self excision of the spacer protein from the Tfp1 precursor. The Tfp1 spacer protein belongs to a new class of intervening sequences that are excised at the protein rather than the RNA level. PMID- 8508781 TI - The Drosophila neurogenic gene neuralized encodes a novel protein and is expressed in precursors of larval and adult neurons. PMID- 8508782 TI - Mossbauer spectroscopy of metalloproteins and the use of Fourier transforms. AB - A method for obtaining accurate, quantitative 57Fe Mossbauer spectra from biological samples is illustrated stepwise in a data reduction procedure. Exact criteria are presented for deciding when it is necessary to account for the effects of the Beer-Lambert law in the Mossbauer spectra from biological samples. This procedure makes extensive use of the fast Fourier transform and other computer techniques in its data reduction and its curve-fitting stages. A method for optimizing sample thickness is presented. The choice of truncation in Fourier space as a means to numerically stabilize the deconvolution procedure is defended. Several advantages for curve fitting in Fourier space are shown. Maximization of information content is discussed for Mossbauer spectral simulation techniques. PMID- 8508783 TI - The glucose-6-phosphate-isomerase reaction is essential for normal glucose repression in Saccharomyces cerevisiae. AB - Wild-type Saccharomyces cerevisiae and a strain carrying a deletion in the glucose-6-phosphate-isomerase gene (pgi1) were grown in carbon-limited continuous cultures on a mixture of fructose and galactose. Pulses of glucose, fructose and galactose were given to these cultures to investigate whether the pgi1 strain was capable of normal glucose repression. Glucose and galactose pulses inhibited fructose consumption and thus glycolysis in the pgi1 strain by a combination of competition between glucose and fructose at the uptake and/or phosphorylation level and inhibition of fructose uptake and/or phosphorylation by glucose 6 phosphate. Fructose pulses administered to the pgi1 strain transiently decreased the glycolytic flux downstream of fructose-1,6-bisphosphate. Transcriptional induction of the PDC1 gene (encoding pyruvate decarboxylase) was observed after glucose or galactose pulses were applied to the pgi1 strain, demonstrating that metabolism of these sugars beyond glucose 6-phosphate is dispensable for PDC1 induction. Fructose also induced PDC1 transcription, indicating that intracellular sugars could act as trigger for PDC1 induction or, alternatively, that two inductors are present. In contrast to the wild-type transcriptional inhibition of the glucose-repressible genes, HXK1 and GAL10 (encoding hexokinase isoenzyme 1 and uridine diphosphoglucose-4-epimerase, respectively) did not occur upon addition of glucose or fructose to the pgi1 mutant. Transcriptional repression was observed after application of the fructose pulse when the yeast had resumed metabolism of fructose. These results demonstrate that the initial signal for catabolite repression is not generated by high sugar concentrations or high concentrations of intermediates; moreover a simple role for the hexokinases can also be excluded. The absence of an increased glycolytic flux in the pgi1 mutant after administration of the sugar pulses while the concentrations of sugar and glycolytic intermediates were high, suggests that the initial signal for glucose repression could be linked to an increased glycolytic flux. The occurrence of PDC1 induction in the pgi1 strain while GAL10/HXKI repression is absent, demonstrates that the initial signals for catabolite induction and catabolite repression are different. PMID- 8508785 TI - Purification and characterization of Thermus caldophilus GK24 DNA polymerase. AB - A thermostable DNA polymerase from Thermus caldophilus GK24 was purified to near homogeneity by chromatographic methods, including ion-exchange, gel-filtration and affinity chromatography. The purified enzyme had a specific activity of 8400 U/mg at 75 degrees C and a molecular mass of 95 kDa, estimated by SDS/PAGE and Superose-12 gel filtration. Reaction conditions were investigated in terms of pH, metal-ion concentration and temperature. Experimental results showed that T. caldophilus (Tca) DNA polymerase had a maximum activity near pH 8.7 at 75 degrees C. The N-terminal sequence of the enzyme was highly similar to that of Thermus aquaticus (Taq) DNA polymerase, which was consistent with the fact that the enzyme had 5'-to-3' exonuclease activity and no 3'-to-5' exonuclease activity. Gene amplification using Tca DNA polymerase resulted in longer products than amplification using Taq DNA polymerase. PMID- 8508784 TI - Factors effecting the thermostability of cysteine proteinases from Carica papaya. AB - Thermal denaturation of four Carica papaya cysteine proteinases (papain, chymopapain, papaya proteinases 3 and 4) was studied as a function of pH using high-sensitivity differential scanning calorimetry. The ratios of calorimetric enthalpy to Van't Hoff enthalpy suggest that, for all these proteins, denaturation occurs as a non two state process, via an intermediate structure. Differences in the thermal stabilities of the proteinases; chymopapain > papaya proteinase 3 > papain > papaya proteinase 4, were correlated to their amino acid sequence to explain the observations in terms of mobility and specific residue mutation. Three-dimensional structures of papain and papaya proteinase 3 were similarly used to illustrate the influence of atomic mobility on stability. PMID- 8508786 TI - Transient and cell-specific expression of tissue-type plasminogen activator and plasminogen-activator-inhibitor type 1 results in controlled and directed proteolysis during gonadotropin-induced ovulation. AB - Proteolytic activity generated by the plasminogen-activator system (PA system) is associated with many biological processes. However, it is not known how the proteolytic activity is regulated in vivo in order to obtain directed proteolysis while, at the same time, protecting unrestrained tissue destruction. Using gonadotropin-induced ovulation as a model, we have studied how two components of the PA system, tissue-type plasminogen activator (tPA) and plasminogen-activator inhibitor type 1 (PAI-1), are regulated temporally and spatially by gonadotropins, leading to the initiation and termination of a well-directed proteolytic process. In-situ hybridization and in-situ zymography were used to analyze the expression of tPA and PAI-1 mRNA and PA-activity in specific ovarian cell types. Both tPA and PAI-1 were found to be regulated and to have a distinct expression pattern in different ovarian compartments. tPA was expressed in both granulosa and thecal-interstitial cells; the highest levels of tPA mRNA were found in the granulosa cells of preovulatory follicles, just prior to ovulation. Consistent with a role for luteinizing hormone/chorionic gonadotropin (LH/CG) in triggering ovulation, the cells and follicles that actively expressed tPA also contained high levels of LH-receptor mRNA while cumulus cells that contain undetectable amounts of tPA mRNA were devoid of LH-receptor expression. The highest levels of PAI-1 mRNA were found about 6 h before ovulation and mainly in the thecal-interstitial cells and ovarian stroma tissue which encapsulate the follicle. Preovulatory follicles, protruding onto the surface of the ovary with less surrounding stroma tissue, expressed less PAI-1 compared to small non ovulatory follicles embedded in inner part of the ovary. In-situ zymography also revealed that the PA activity was colocalized to the surface of the ovary just prior to ovulation. Our studies suggest that a proteolytic activity provided by tPA and modulated by PAI-1 is responsible for a controlled and directed proteolysis leading to rupture of selected follicles during ovulation. PMID- 8508787 TI - Relationships between alkali light-chain complement and myosin heavy-chain isoforms in single fast-twitch fibers of rat and rabbit. AB - The present study compares the alkali myosin light chain (LC) complement of the fast fiber types IIB, IID and IIA in single fibers from rat muscle, as well as in type IID and type IIA fibers from rabbit muscle. Single fibers were classified according to their electrophoretically determined myosin heavy chain (HC) isoforms, HCIIb, HCIId, and HCIIa. Alkali myosin light chains were analysed by densitometric evaluation of two-dimensional electrophoresis performed on extracts from the same fibers. On the average, the fraction of LC3f, i.e. LC3f/(LC1f+LC3f), was highest in type IIB fibers and lowest in type IIA fibers. Type IID fibers occupied an intermediate position. Also in the rabbit, type IID fibers displayed a higher fraction of LC3f than type IIA fibers. Large scattering of the LC3f fraction in IIB, IID, and IIA fibers indicated that each fiber type is composed of fibers identical with regard to their specific myosin heavy chain complement, but heterogeneous with regard to their fast alkali light chain composition and the resulting light-chain-based isomyosins. It is suggested that the variable proportions of the two alkali light chains in the three fast fiber populations serve as a fine tuning of contractile velocities within the ranges determined by the three fast myosin heavy-chain isoforms. PMID- 8508788 TI - Interactions between glucose metabolism and oxidative phosphorylations on respiratory-competent Saccharomyces cerevisiae cells. AB - The purpose of this work was to analyze the interactions between oxidative phosphorylations and glucose metabolism on yeast cells aerobically grown on lactate as carbon source and incubated in a resting cell medium. On such respiratory-competent yeast cells, four different metabolic steady states have particularly been studied: (a) glucose feeding under anaerobiosis, (b) ethanol supply under aerobiosis, (c) glucose supply under aerobiosis and (d) glucose plus ethanol under aerobiosis. For each condition, we measured: (a) the cellular ATP/ADP ratio and NADH content sustained under these conditions, (b) the glucose consumption rate (glucose conditions) and the respiratory rate (aerobic conditions). Under aerobic conditions, when ethanol is used as substrate, the ATP/ADP ratio and NADH level are very high as compared with glucose feeding. However, the rate of oxygen consumption is similar under both conditions. The main observation is a large increase in the respiratory rate when both glucose and ethanol are added. This increase corresponds to an ATP/ADP ratio and a NADH level lower than those observed with ethanol but higher than those with glucose. Therefore the response of the respiratory rate to the ATP/ADP ratio depends on the redox potential. We studied the way in which the ATP-consuming activity was increased under glucose+ethanol conditions. By NMR experiments, it appears that neither the futile cycle at the level of the phosphofructo-1-kinase/fructo-1,6 bisphosphatase couple nor the synthesis of carbohydrate stores could account for the increase in oxidative phosphorylation. However, it is shown that, in the presence of glucose+ethanol, ATP consumption is strongly stimulated. It is hypothesized that this consumption is essentially due to the combination of the well-known plasma membrane proton-ATPase activation by glucose and the high phosphate potential due to oxidative ethanol metabolism. While it is well documented that oxidative phosphorylations inhibit the glycolytic flux, i.e. the Pasteur effect, we clearly show in this work that the glycolytic pathway limits the ability of mitochondria to maintain a cellular phosphate potential. PMID- 8508790 TI - Cannabinoid-receptor expression in human leukocytes. AB - Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery. Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes. The distribution pattern displays important variations of the mRNA level for the cannabinoid receptor among the main human blood cell subpopulations. The rank order of mRNA levels in these cells is B cells > natural killer cells > or = polymorphonuclear neutrophils > or = T8 cells > monocytes > T4 cells. Cannabinoid-receptor mRNA, which is also found in monocytic, as well as T and B leukemia cell lines but not in Jurkat cells, presents a great diversity of expression on these cells as well, B-cell lines expressing a much higher level than T-cell lines. The cannabinoid receptor PCR products from leukocytes and brain are identical both in size and sequence suggesting a strong similarity between central and peripheral cannabinoid receptors. The expression of this receptor was demonstrated on membranes of the myelomonocytic U937 cells using the synthetic cannabinoid [3H]CP-55940 as ligand. The Kd determined from Scatchard analysis was 0.1 nM and the Bmax for membranes was 525 fmol/mg protein. The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells. PMID- 8508789 TI - Molecular cloning and nucleotide sequence of cDNA encoding rat kidney long-chain L-2-hydroxy acid oxidase. Expression of the catalytically active recombinant protein as a chimaera. AB - Long-chain L-alpha-hydroxy acid oxidase from rat kidney is a member of the family of FMN-dependent alpha-hydroxy-acid-oxidizing enzymes. With the knowledge of the recently determined amino acid sequence, the cDNA encoding the enzyme has now been cloned using the polymerase chain reaction. The 1648-bp cDNA contains an open reading frame coding for the 352 residues of the previously determined sequence, preceded by a methionine codon. In addition, several clones were found to present a nine-base insertion, predicting the existence of an isoform with a tripeptide VRK inserted between residues 188 and 189 of the mature protein. The presence of about 10% of this isoform in the oxidase purified from rat kidney was indeed identified by amino acid sequencing. A recombinant active enzyme was obtained as a protein fused to glutathione S-transferase using the bacterial expression plasmid pGEX-3X. Physico-chemical characterization indicated, for the fused enzyme, properties similar to those of the rat kidney protein. When the chimaera was submitted to factor Xa, proteolysis at the engineered cleavage point was poor. Separation of hydroxy acid oxidase from glutathione S-transferase could not be achieved with trypsin either. With both proteases, the initial cleavage point appeared to be in a peptide loop internal to the hydroxy acid oxidase sequence, close to or in the tripeptide insertion locus and not at the engineered factor-Xa-cleavage point. Comparative tryptic proteolysis of the rat kidney enzyme yielded a form cleaved in the same loop. PMID- 8508791 TI - Molecular cloning of silkworm (Bombyx mori) antichymotrypsin. A new member of the serpin superfamily of proteins from insects. AB - The cDNA of silkworm (Bombyx mori) antichymotrypsin (sw-Achy) was cloned from larval fat body and its nucleotide sequence was determined. The deduced amino acid sequence of mature sw-Achy begins with Phe1 and ends with Phe384, with a preceding 16-amino-acid signal peptide. The amino-acid sequence similarities of sw-Achy with the serine-proteinase inhibitors (serpins) silkworm antitrypsin, tobacco hornworm alaserpin, human alpha-1-antitrypsin and human alpha-1 antichymotrypsin were 29.6%, 30.3%, 26.1%, and 25.0%, respectively. The highly conserved amino acids in other serpins are also conserved in sw-Achy. sw-Achy is thought to be a new member of the serpin family. Multiple alignment of sw-Achy with 23 other kinds of serpin by the progressive method produced a phylogenetic tree in which all four insect serpins are grouped separately within one branch. The reactive site of sw-Achy with alpha-chymotrypsin was identified as Thr343 Ser344 by direct amino-acid sequence analysis of cleaved and purified protein. PMID- 8508792 TI - Catalytic antibody activity elicited by active immunisation. Evidence for natural variation involving preferential stabilization of the transition state. AB - 1. The hydrolytic activity of IgG purified from (a) 13 samples of ovine antiserum collected from three animals during a two-year immunisation programme using a phosphate immunogen (comprising the amide conjugate bonded through the carboxy group of 4-nitrophenyl 4-carboxymethylphenyl hydrogen phosphate and amino groups of keyhole-limpet haemocyanin) and (b) a sample of ovine antiserum collected from another animal during an 18-week immunisation programme using an analogous sulphone immunogen (comprising the amide conjugate bonded through the amino group of 4-nitrobenzyl, 4-(4-aminobutoxy)benzyl sulphone and carboxyl groups of keyhole limpet haemocyanin) were evaluated kinetically by using 4-nitrophenyl 4-(3-aza-2 oxoheptyl)phenyl carbonate and 4-nitrophenyl 4-(2-hydroxyethoxy)phenyl carbonate as substrates. 2. Catalytic activity was found in all 13 samples of anti phosphate IgG but was absent in the sample of anti-sulphone IgG as well as in all samples of IgG isolated from the serum of non-immunised animals. These findings, taken together with the lack of catalytic activity of the anti-phosphate IgG towards the 2-nitrophenyl 4-(3-aza-2-oxoheptyl)phenyl carbonate, compel the view that the catalytic activity of the anti-phosphate IgG preparation is entirely antibody-mediated and is not due to contaminant hydrolytic enzymes. The fact that catalytic activity was found in all 13 samples of the anti-phosphate IgG provides the first evidence that it is possible, as a routine, to elicit a catalytic antibody response in a host animal via active immunisation. 3. The nature of the, albeit small, variation in the catalytic characteristics of the anti-phosphate IgG (increase in both kcat, the catalytic rate constant calculated as V/2[IgG] and kcat/Km, the apparent second-order rate constant for the overall catalysed conversion of substrate to products, with increase in Km suggests simultaneous improvement in transition state binding and deterioration in substrate binding as predicted from immunogen design and the postulated general mechanistic basis of antibody catalysis. 4. This interpretation is supported by the difference in the values of the dissociation constant Ki for the competitive inhibition by the transition-state analogue 4-methylphenyl 4-nitrophenyl hydrogen phosphate of reactions catalysed by two representative anti-phosphate IgG samples: for the catalysis with Km = 4.5 microM, Ki = 9 nM and for that with Km = 1.3 microM, Ki = 80 nM.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8508793 TI - Characterization of the Actinobacillus pleuropneumoniae serotype K11:01 capsular antigen. AB - The capsular antigen of Actinobacillus pleuropneumoniae serotype 11 was characterized by one-dimensional high-field nuclear magnetic resonance methods and chemical analyses, as a teichoic-acid-type polymer composed of a repeating unit with the structure [see text]. PMID- 8508794 TI - Implications of the three-dimensional structure of astacin for the structure and function of the astacin family of zinc-endopeptidases. AB - Astacin, a zinc-endopeptidase from the crayfish Astacus astacus L., represents a structurally distinct group of metalloproteinases termed the 'astacin family'. This protein family includes oligomeric membrane-bound proteins with zinc proteinase domains found in rodent kidneys (meprins A and B) and human small intestine (N-benzoyl-L-tyrosyl-4-aminobenzoate hydrolase). Another branch of this family comprises morphogenetically active proteins, which induce bone formation (human bone morphogenetic protein 1), or which play specific roles during the embryonic development of amphibians, fishes, echinoderms, and insects. The X-ray crystal structure of astacin has recently been solved to a resolution of 0.18 nm [Bode et al. (1992) Nature 358, 164-167]. This structure is different from hitherto known metalloendopeptidase structures and has been used in the present study to analyze the structures of the other members of the astacin protein family. Computer-assisted modelling of the proteolytic domain of the alpha subunit of meprin A based on the astacin structure is possible if five single and one double residue deletions and three single residue insertions are implied. The proteinase domains of the other astacins can be included in the model-based sequence alignment by introducing additionally three insertions and one deletion. All of these insertions and deletions are observed in loop segments connecting regular secondary structure elements and should leave the overall structure unaltered. The topology of residues forming the zinc-binding active site of astacin corresponds to almost identical arrangements in all other astacins, suggesting that these are likewise metalloproteinases. Based on this similarity, it is proposed that the active-site metal ion of the astacins is penta coordinated by three histidine residues, a tyrosine residue and a water molecule in a trigonal bipyramidal geometry. Other remarkable common features are a hydrophobic cluster in the N-terminal domain and a conserved, solvent-filled cavity buried in the C-terminal domain. Most interestingly, the amino-termini of all astacins can be modelled to start in a corresponding internal water cavity as seen in the astacin template, where the terminal alanine residue forms a water linked salt bridge to Glu103, directly adjacent to His102, the third zinc ligand. Therefore, an activation mechanism for the astacins reminiscent of that of the trypsin-like proteinases had been suggested, which now seems to be probable also for the other astacins. Besides these common traits, there are some minor differences which may have important consequences on the function of the astacins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8508795 TI - Hyperammonemia decreases protein-kinase-C-dependent phosphorylation of microtubule-associated protein 2 and increases its binding to tubulin. AB - Hyperammonemia increases the polymerization of brain microtubules, which is controlled by the binding of microtubule-associated protein (MAP) 2; binding of MAP-2 is, in turn, regulated by phosphorylation. We have found that the binding of MAP-2 to tubulin is greatly increased by hyperammonemia, however, the brain content of MAP-2 is not affected. Microtubules isolated from hyperammonemic rats contained approximately twice the MAP-2/mg microtubular protein that of microtubules isolated from control animals. MAP isolated from brain microtubules of hyperammonemic rats stimulated the polymerization of tubulin more than MAP isolated from control animals. This appears to be due to the increased content of MAP-2. In vitro phosphorylation, using brain homogenates, showed that protein kinase-C-dependent phosphorylation of MAP-2 was markedly decreased in hyperammonemic rats. Hyperammonemia also affected the intracellular distribution of brain protein kinase C; its content in the cytosol increased about 23%, while in membranes it decreased by 46%. The possible role of decreased protein-kinase-C dependent phosphorylation on the increased binding of MAP-2 to tubulin and in the increased polymerization of microtubules in the brain of hyperammonemic rats is discussed. PMID- 8508796 TI - Molecular cloning, sequence analysis and expression of the gene for catalase peroxidase (cpeA) from the photosynthetic bacterium Rhodobacter capsulatus B10. AB - The gene encoding catalase-peroxidase was cloned from chromosomal DNA of Rhodobacter capsulatus B10. The nucleotide sequence of a 3.7-kb SacI-HindIII fragment, containing the catalase-peroxidase gene (cpeA) and its flanking regions were determined. A 1728-bp open reading frame, coding for 576 amino acid residues (molecular mass 61516 Da) of the enzyme, was observed. A Shine-Dalgarno sequence was found 5 bp upstream from the translational start site. The deduced amino acid sequence coincides with that of the amino terminus and of four peptides derived from trypsin digestion of the purified catalase-peroxidase of R. capsulatus B10. The amino acid sequence of R. capsulatus catalase-peroxidase shows interesting similarities to the amino acid sequences of the hydroperoxidases of Escherichia coli (42.7%) and Salmonella typhimurium (39.9%), the peroxidase of Bacillus stearothermophilus (32.1%) and the catalase-peroxidase of Mycobacterium intracellulare (42.2%). As shown by a cpeA::lacZ fusion in trans in R. capsulatus, the expression of the catalase-peroxidase gene is regulated by oxygen. The promoter of the cpeA gene was localized within 320 bp upstream of the ATG start codon. PMID- 8508797 TI - Chemoattractants for neutrophils in lipopolysaccharide-induced inflammatory exudate from rats are not interleukin-8 counterparts but gro-gene product/melanoma-growth-stimulating-activity-related factors. AB - Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides. PMID- 8508798 TI - Genomic organization, splice variants and expression of CGM1, a CD66-related member of the carcinoembryonic antigen gene family. AB - The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunoglobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGM1, a transmembrane member of the CEA family without immunoglobulin constant-like domains. CGM1a and CGM1c contain cytoplasmic domains of 71 and 31 amino acids, respectively. The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp) leads to the formation of CGM1c. The presence or absence of potential protein kinase phosphorylation sites in the cytoplasmic domains and a sequence consensus motif involved in signal transduction in multichain immune recognition receptors indicates that this splice event is of functional importance. CGM1a mRNA, the predominant CGM1 transcript, was found in the granulocytic lineage, but not in monocytes, lymphocytes nor in a number of tumors derived from all three germ layers. Weak staining using monoclonal antibodies Tu2 and 73 in fluorescence activated cell scan analyses indicate low concentrations of CGM1 protein on the surface of granulocytes. The CGM1 protein is also recognized by CD66 antibodies. Therefore, the granulocyte-specific CD66 epitope is present on at least four CEA family members: CGM1, CEA, NCA-50/90 and NCA-160. PMID- 8508799 TI - Efficient secretion of attacin from insect fat-body cells requires proper processing of the prosequence. AB - The attacins constitute a group of immune proteins induced after bacterial infection in the moth Hyalophora cecropia. They are synthesized as preproproteins and undergo post-translational modification during transport to the hemolymph. The processing and transport rates of attacin were studied in its natural host as a response to infection. Monensin totally inhibited the processing from proattacin to attacin and the radiolabeled proattacin remained intracellular. This observation indicated that the prosequence is removed at or after the trans Golgi compartment. It is also suggested that the processing of the prosequence does not occur in acidic vesicles, as the process was not inhibited by the weak base chloroquine. To study prosequence function, the attacin gene and genes with mutations in the prosequence were cloned into the baculovirus Autographa californica nuclear polyhedrosis virus. The processing of proattacin and the transport of attacin were studied by pulse-chase experiments with fat body isolated from Trichoplusia ni larvae. The rate of secretion from fat body was lowest for proattacin, which could not be processed to attacin, intermediate for attacins lacking the prosequence and highest for natural attacin. We could not detect any biological activity for proattacin. PMID- 8508800 TI - Heterologous expression in Escherichia coli of an intact multienzyme component of the erythromycin-producing polyketide synthase. AB - 6-Deoxyerythronolide B synthase 3 (DEBS 3) is proposed to catalyse the fifth and sixth condensation cycles in the assembly of the polyketide 6-deoxyerythronolide B, the first isolatable intermediate in the biosynthesis of erythromycin A by Saccharopolyspora erythraea. The gene encoding DEBS 3 has previously been cloned and sequenced, and the deduced product is predicted to house nine fatty acid synthase-like activities on a 330-kDa polypeptide chain. The gene has been engineered into a pT-7-based expression system for over-expression in Escherichia coli. Recombinant DEBS 3 was found to constitute, after induction, 1-2% of soluble intracellular protein. DEBS 3 was purified from extracts of the recombinant E. coli to apparent homogeneity, and was found not to be modified by covalent attachment of the prosthetic group 4'-phosphopantetheine. Incubation with (R,S)-methylmalonyl-CoA, the presumed source of extension units for polyketide chain assembly, led to hydrolysis of the thioester, implying that the methylmalonyl-CoA:ACP acyltransferase domains in DEBS 3 are correctly folded and able to catalyse this side-reaction. During this reaction, DEBS 3 became transiently radiolabelled, consistent with the intermediacy of an acylenzyme. The native molecular mass of the protein by gel filtration chromatography was 668 kDa which corresponds either to a dimer or to a highly asymmetric monomer. PMID- 8508801 TI - Zn-exchange and Mossbauer studies on the [Fe-Fe] derivatives of the purple acid Fe(III)-Zn(II)-phosphatase from kidney beans. AB - In order to perform Mossbauer studies, Zn(II) in the Fe(III)-Zn(II) purple acid phosphatase of the red kidney bean has been exchanged by incubating the semiapoenzyme with 57Fe(II). The resulting Fe(III)-57Fe(II) enzyme has 125% activity, compared with that of the Zn(II) enzyme. It can be oxidized by H2O2 or peroxydisulfate to the Fe(III)-57Fe(III) species with a 30-times lower activity. Incubation of the metal-free apoenzyme with 57Fe(II) in the presence of O2 leads to the 57Fe(III)-57Fe(II) species which is stable in dilute solutions, but partially oxidized during the concentration procedure to the 57Fe(III)-57Fe(III) enzyme. Limited reduction of the oxidized enzyme with ascorbate delivers a mixture of the Fe(II)-Fe(II)/Fe(III)-Fe(III) species, but not the mixed valent Fe(III)-Fe(II) species, indicating that after the transfer of the first electron the second electron of the ascorbate radical is immediately transferred to the second Fe(III). The Mossbauer spectra of the oxidized species show at 4.2 K two quadrupole doublets with delta of 0.51 mm/s and 0.53 mm/s and delta E of 1.46 and 0.96 mm/s indicating high spin Fe(III) in two different binding sites, obviously with a higher asymmetry in the chromophoric Fe(III) site. The values are too low for a mu-oxo bridge. The mixed-valent Fe(III)-Fe(II) species shows two quadrupole doublets with delta values of 0.55 mm/s and 1.14 mm/s and delta E values of 1.43 mm/s and 3.01 mm/s at 70 K for high spin Fe(II) and Fe(III), but the signal of the Fe(II) component shows magnetic patterns at 4.2 K indicating a half-integer spin system with antiferromagnetic coupling. The Fe(II)-Fe(II) system exhibits two quadrupole doublets with delta values of 1.18 mm/s and 1.22 mm/s and with delta E values of 3.69 mm/s and 2.68 mm/s again indicating a higher asymmetry in the originally chromophoric Fe(III)-binding site. Addition of phosphate shows only minor differences in the oxidized enzyme and in the mixed valent Fe(III) Fe(II) system. Interaction with O2 is discussed. PMID- 8508802 TI - Characterization of a transcriptional control element involved in proliferation of peroxisomes in yeast in response to oleate. AB - Oleate induces the transcription of genes involved in peroxisome biogenesis and stimulates the proliferation of these organelles in Saccharomyces cerevisiae. Previously, we have reported the identification of a region containing a positive regulatory element in the 5' flanking region of the FOX3 gene encoding the peroxisomal enzyme 3-oxoacyl-CoA thiolase. This region contains a 23-bp imperfect inverted-repeat sequence. Full induction, in response to oleate, is mediated by the intact dyad. However, one half-site of the inverted repeat is also able to mediate induction of transcription in response to oleate, albeit to a small extent. Furthermore, the weak binding of protein to each part of the inverted repeat proved to be correlated with the weak activation of transcription, in support of oleate. A DNase-I footprint covered the entire dyad and DNA band-shift experiments indicated that one or more trans-acting factors bind to the imperfect palindrome. The binding of protein to this element seems to be correlated with transcriptional activation, since mutations in both halves of the inverted dyad affected both transcriptional activation and protein binding in vitro. Similar oleate-responsive elements are commonly found in the 5' flanking regions of genes encoding proteins involved in peroxisome biogenesis and the factor(s) binding to oleate-responsive element(s) could therefore be involved in coordination of the expression of oleate-inducible genes and the proliferation of peroxisomes. PMID- 8508803 TI - Sex pheromone plasmid pAD1-encoded aggregation substance of Enterococcus faecalis is positively regulated in trans by traE1. AB - Sex-pheromone-plasmid-bearing strains of Enterococcus faecalis react with sex pheromone to induce the expression of an adhesin, the so-called aggregation substance, on their cell surface. Here we show that, by complementation studies, for sex-pheromone plasmid pAD1, expression of the structural gene asa1, coding for an aggregation substance, is mediated by a diffusible factor encoded on pAD1. We were able to demonstrate that a small open reading frame, traE1, is sufficient for transcription of the operon containing asa1. A model for expression of asa1 under the influence of the positive regulator is presented, which is supported by our observation that regulation involves an all-or-nothing induction phenomenon, leading to cells either fully expressing asa1 or not at all. PMID- 8508804 TI - Dye-linked L-malate dehydrogenase from thermophilic Bacillus species DSM 465. Purification and characterization. AB - The distribution of dye-linked L-malate dehydrogenase (L-malate: acceptor oxidoreductase, EC 1.1.99.16) was investigated in many thermophilic bacteria. The enzyme occurred widely in thermophilic spore-forming bacteria like bacilli and thermoactinomycetes. The enzyme was purified to homogeneity from a thermophile, Bacillus sp. DSM 465, with a 2.7% overall recovery by DEAE-Toyopearl column chromatography, Sephacryl S-400 column chromatography and preparative slab PAGE. The enzyme had a molecular mass of about 660 kDa and consisted of about ten subunits all with a molecular mass of 66 kDa. The enzyme retained its full activity upon heating at 55 degrees C for at least 60 min and with incubation at pH 5.0-10.0, 55 degrees C, for 10 min. The enzyme exclusively catalyzed L-malate dehydrogenation in the presence of an electron acceptor such as 2,6 dichloroindophenol. The Michaelis constants for L-malate and 2,6 dichloroindophenol were determined to be 1.67 mM and 0.050 mM, respectively. FAD was identified as a prosthetic group of the enzyme by HPLC. PMID- 8508805 TI - Functional expression of D-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic eubacterium Thermotoga maritima in Escherichia coli. Authenticity and kinetic properties of the recombinant enzyme. AB - The gene coding for D-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic eubacterium Thermotoga maritima has been cloned and functionally expressed in Escherichia coli. Some 90% of the coding gene was amplified by the polymerase chain reaction. The amplified gene segment was in full agreement with the previously determined amino acid sequence [Schultes, V., Deutzmann, R., Jaenicke, R. (1990) Eur. J. Biochem. 192, 25-31] and was completed by the insertion of synthetic linkers using site-directed mutagenesis. The resulting semisynthetic gene was expressed in high yield in the cytoplasm of E. coli and the recombinant enzyme was purified to homogeneity. It was shown to be identical with the enzyme isolated directly from T. maritima in all enzymatic and physicochemical properties investigated. The enzyme is allosterically inhibited by both D- and L-glyceraldehyde 3-phosphate at concentrations above 1 mM, and by arsenate at concentrations above 10 mM. The expressed protein restores the natural E. coli phenotype in a gap- strain, thus providing evidence that the hyperthermophilic protein can fold and associate to its native, functional state in its mesophilic host. PMID- 8508806 TI - Biochemical bases of the interaction of human basic fibroblast growth factor with glycosaminoglycans. New insights from trypsin digestion studies. AB - In the present study we have attempted a characterization of the biochemical bases of the interaction of human basic fibroblast growth factor (bFGF) with glycosaminoglycans (GAGs) in solution. This interaction has been evidenced as the capacity of different GAGs and various sulfated compounds to protect bFGF and different bFGF mutants from tryptic cleavage. Heparin protects bFGF from trypsin digestion in a dose-dependent fashion. Substitution by site-directed mutagenesis of two or more basic residues with neutral glutamine residues in the amino terminal region bFGF(27-32) or in the carboxyl-terminal region bFGF(118-129) does not significantly affect the protective effect exerted by heparin. In contrast, heparin protection is abolished when the full region bFGF(27-32) is deleted. The capacity of different GAGs to protect bFGF from proteolytic cleavage decreases in the following order: heparin > heparan sulfate > dermatan sulfate = chondroitin sulfates A and C > hyaluronic acid = K5 polysaccharide, indicating that both the degree of sulfation and the backbone structure of GAG modulate its interaction with bFGF. This is confirmed by the different capacity of various sulfated compounds (including dextran sulfates, suramin, trypan blue, and sulfate ion) to protect bFGF from tryptic digestion. Moreover, tryptic digestion studies performed with various heparin molecules and dextran sulfates of different size, ranging from 2.0 kDa to 500 kDa, indicate that the number of bFGF molecules which interact with a single molecule of polysaccharide is related to the molecular mass of the GAG and that six hexose residues are sufficient to protect 1-2 molecules bFGF. In conclusion, our findings indicate that the capacity of GAGs to protect bFGF from tryptic cleavage depends upon their size, sulfation, distribution of the anionic sites along the chain, and structural requirements of the bFGF molecule. These studies will help to design synthetic oligosaccharides endowed with different bFGF agonist and/or antagonist activities. PMID- 8508807 TI - Site directed mutagenesis of DNA polymerase I (Klenow) from Escherichia coli. The significance of Arg682 in catalysis. AB - We have reported that a domain containing Arg682 in the Klenow fragment of Escherichia coli DNA polymerase I (pol I) is important for the template-dependent dNTP-binding function [Pandey, V.N., Kaushik, N. A., Pradhan, D. S. & Modak, M. J. (1990) J. Biol. Chem. 265, 3679-3884]. In order to further define the role of Arg682 in the catalytic process, we have performed site-directed mutagenesis of this residue. For this purpose the Klenow-coding region of the DNA-pol-I gene was selectively amplified from the genomic DNA of E. coli and was cloned in an expression vector, pET-3a. This clone under appropriate conditions overproduces the Klenow fragment in E. coli. Using this clone (pET-3a-K) as the template, two mutant polymerase clones were constructed in which arginine has been replaced with either alanine, [R682A] pol I, or lysine [R682K] pol I. Both mutant enzymes showed significantly lower specific activity as compared to the wild-type enzyme. The kinetic analyses of the mutant enzymes indicated a 3-4-fold increase in the Km for the substrate dNTP, a 20-25-fold decrease in the Vmax and an overall decrease in the processive nature of DNA synthesis in both the mutant enzymes. The reverse mutation of Ala682 to the wild-type form Arg682 fully restored the processive nature and the polymerase activity of the enzyme. These observations suggest that the positively charged guanidino group in the side chain of Arg682 is catalytically important but not absolutely essential for synthesis of DNA. Furthermore it appears to maintain high processivity of the DNA synthesis catalyzed by the enzyme. PMID- 8508808 TI - Mass determination of 15-hydroxyprostaglandin dehydrogenase from human placenta and kinetic studies with (5Z, 8E, 10E, 12S)-12-hydroxy-5,8,10-heptadecatrienoic acid as substrate. AB - NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase catalyzes the first step in the metabolism of prostaglandins which is usually associated with physiological inactivation. A highly purified homogenous enzyme preparation from human placenta was used to determine the molecular mass and lack of quaternary structure of the enzyme. Furthermore we have examined enzyme kinetics of the purified enzyme with (5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) an equimolar coproduct of thromboxane biosynthesis. Using gel electrophoresis and gel filtration on FPLC, we could estimate a molecular mass of 28 +/- 1 kDa, indicating that the enzyme consists of one single protein chain. The exact molecular mass of the monomer was calculated by matrix-assisted laser desorption/ionization mass spectrometry to 28740 +/- 30 Da. (5Z,8E,10E)-12-oxo 5,8,10-heptadecatrienoic acid (oxo-HT) could be identified as the only product obtained from the enzymatic reaction with HHT. Quantification of this metabolite was achieved by gas chromatography/tandem mass spectrometry. The calculated enzyme kinetic constants for the formation of the metabolic product [Km (HHT) = 9.68 microM, Vi = 12.78 mU/micrograms] were in agreement with those determined for NADH formation (Km = 7.65 microM, Vi = 11.79 mU/micrograms). This demonstrates that HHT shows high affinity to the enzyme which is comparable to prostaglandin E2 (PGE2). As the product oxo-HT is a potent inhibitor of platelet aggregation, dehydrogenation of HHT might represent a biological activation step. PMID- 8508809 TI - Does Escherichia coli possess a second citrate synthase gene? AB - Escherichia coli possesses a hexameric citrate synthase that exhibits allosteric kinetics and regulatory sensitivity, and for which the gene (gltA) has previously been cloned and sequenced. A citrate-synthase-deficient strain of E. coli (K114) has been mutated to generate a revertant (K114r4) that produces a dimeric citrate synthase with altered kinetic and regulatory properties. On cloning and sequencing the gltA gene from both K114 and K114r4, a single mutation was found that caused the replacement of Asp362 with Asn. Asp362 has been previously shown to be a catalytically essential residue in E. coli citrate synthase, and we demonstrate that the hexameric enzyme produced on expression of the gltA gene from K114 and K114r4 is inactive. The dimeric citrate synthase from K114r4 has been purified and shown to be immunologically distinct from the wild-type hexameric enzyme. Determination of its N-terminal amino acid sequence demonstrates that the mutant citrate synthase is encoded by a gene distinct from the E. coli gltA gene. The N-terminal sequence is compared with those of other eukaryotic, eubacterial and archaebacterial citrate synthases. PMID- 8508810 TI - Structural analysis of periplasmic carbonic anhydrase 1 of Chlamydomonas reinhardtii. AB - Periplasmic carbonic anhydrase 1 of the unicellular green alga Chlamydomonas reinhardtii is a heterotetrameric glycoprotein consisting of two large subunits and two small subunits [Kamo, K., Shimogawara, K., Fukuzawa, H., Muto, S. & Miyachi, S. (1990) Eur. J. Biochem. 192, 557-562]. The cDNA sequence showed that the two subunits are cotranslated as a 377-amino-acid precursor polypeptide (41.6 kDa) consisting of an N-terminal 20-amino-acid signal peptide, a large subunit (35.6 kDa) and a small subunit (4.1 kDa) [Fukuzawa, H., Fujiwara, S., Yamamoto, Y., DionisioSese, M. L. & Miyachi, S. (1990) Proc. Natl Acad. Sci. USA 87, 4383 4387]. In the present study, amino-acid-sequence analysis of the carbonic anhydrase 1 was carried out to determine the sites of disulfide bonds and N glycosylation and the C-terminal amino acid of the large subunit. Disulfide bonds were detected between Cys21 and Cys21, Cys61 and Cys264, Cys194 and Cys198, and Cys296 and Cys351 in the amino acid sequence deduced from the cDNA. Cys21 and Cys21 link two large subunits and Cys296 and Cys351 link a large subunit to a small subunit. Thus, the holoenzyme is constructed of two disulfide-bound large subunits, each of which joins to a small subunit by a disulfide bond. The C terminal amino acid residue of the large subunit was determined as Ala305. This indicates that the peptide consisting of 35 amino acid residues between the large and the small subunit is deleted from the precursor during maturation, since the N-terminus of the small subunit is Ala341. Three potential N-glycosylation sites in the large subunit were all glycosylated. PMID- 8508811 TI - Molecular characterization of Limulus polyphemus C-reactive protein. I. Subunit composition. AB - The molecular mass of whole native C-reactive protein (CRP) from Limulus polyphemus, the horseshoe crab, was precisely determined for the first time, by analytical ultracentrifugation after measurement of its absorption coefficient, A1cm, 1% at 280 nm (15.49) and its partial specific volume (0.72 +/- 0.003 ml/g). The apparent weight-average molecular mass, in the range over which it was independent of the concentration, was 300 kDa. Limulus CRP, isolated from an individual animal, was also analyzed by electrospray mass spectrometry after dissociation into its subunits, and nine components were detected in the mass range 24935-25617 Da. Four of these components corresponded precisely to one of the previously reported protein sequences of Limulus CRP subunits which is glycosylated by a single oligosaccharide chain of composition, Man2GlcNAc2, Man3GlcNAc2, Man4GlcNAc2 or Man5GlcNAc2, the structures of which are elucidated in the accompanying paper [Amatayakul-Chantler, S., Dwek, R. A., Tennent, G. A., Pepys, M. B. & Rademacher, T. W. Molecular characterization of Limulus polyphemus C-reactive protein. II. Asparagine-linked oligosaccharides (1993) Eur. J. Biochem. 214, 99-110]. All the remaining components, except one minor component, corresponded to the analogous glycoforms of peptides of molecular mass 24281 +/- 2 Da and 24523 +/- 1 Da, neither of which have previously been characterized. These results are consistent with the presence of 12 subunits in the Limulus CRP molecule, in contrast to the number of subunits in vertebrate members of the CRP family. The CRP family members in vertebrates are known as pentraxins because of the symmetrical pentameric arrangement of their subunits. The concentration of Limulus CRP in hemolymph from 20 individual animals, measured precisely by specific electroimmunoassay, covered the wide range 0.275-6.64 mg/ml, mean (SD) = 1.83 (2.06) mg/ml. It remains to be determined whether this protein is an acute phase reactant, like its human and some other mammalian homologues. PMID- 8508812 TI - Molecular characterization of Limulus polyphemus C-reactive protein. II. Asparagine-linked oligosaccharides. AB - The N-linked oligosaccharides of C-reactive protein (CRP) from the arachnid Limulus polyphemus, the horseshoe crab, were characterized after their release by hydrazinolysis, re-N-acetylation, and reduction with NaB3H4. High-voltage paper electrophoresis of the reduced oligosaccharides revealed only neutral species. Gel-permeation chromatography on Bio-Gel P4 yielded five fractions. The oligosaccharide fractions were further fractionated using high-voltage borate paper electrophoresis and Dionex BioLC ion-exchange chromatography. The oligosaccharides were structurally characterized by sequential exoglycosidase digestion, fragmentation by acetolysis and methylation analysis. Three major structures were found, of which two were the biantennary oligomannose type with compositions Man5GlcNAc2 (B-1), Man4GlcNAc2 (C-3) and one was the monoantennary structure Man3GlcNAc2 (D-1). The biantennary oligomannose structures B-1 and C-3 contained the structural unit Man alpha 6Man alpha 6R. This unusual arrangement of mannose linkages suggests a biosynthetic pathway in Limulus which differs from that reported in mammals, plants and the parasitic protozoa. PMID- 8508813 TI - Incidence of listeriosis in Barcelona, Spain, in 1990. The Collaborative Study Group of Listeriosis of Barcelona. AB - A population-based register of cases of listeriosis admitted to acute-care hospitals has been established in Barcelona, Spain, in order to estimate the basal incidence of sporadic cases and to facilitate epidemiological surveillance of potential epidemics. Eleven acute-care hospitals reported all cases of listeriosis to a central unit following a standardized protocol. During 1990, 31 patients with listeriosis were identified, 18 of whom were residents of the city, resulting in an annual incidence of 10.95 cases per million inhabitants. Twelve of the 31 cases occurred in the period from July to September 1990, ten of them being community-acquired. The incidence of listeriosis was higher in elderly (> or = 65 years) and immunosuppressed persons. Forty-two percent of the cases were considered to be nosocomial infections. The overall mortality rate was 51.6%. The incidence of listeriosis in the present study is one of the highest reported in the literature. A high sensitivity of the reporting system with good case identification techniques, or demographic and environmental characteristics related to Listeria monocytogenes infection in our area, might be possible reasons for this geographic variation. PMID- 8508814 TI - Characterization of Listeria strains from a foodborne listeriosis outbreak by rDNA gene restriction patterns compared to four other typing methods. AB - The rDNA gene restriction patterns of 134 isolates of Listeria species were determined with pKK3535--a pBR322 derived plasmid containing an Escherichia coli rRNA operon--used as a probe following digestion of chromosomal DNA by EcoRI endonuclease. Nineteen reference and type strains representing all species and serotypes of Listeria showed 17 distinct ribotypes. One hundred and fifteen wild strains of Listeria monocytogenes were ribotyped and the results were compared to those of serotyping, phage typing, multilocus enzyme electrophoresis (MEE) and restriction endonuclease analysis (REA). Ninety-six Listeria monocytogenes serotype 4b wild strains displayed six distinct ribotypes (I-VI), 72% (69/96) of them clustering in two very close rDNA patterns (I and II) of eight and nine bands, respectively. The same 96 strains displayed six REA patterns and eight MEE electrotypes. Among the 96 Listeria monocytogenes 4b isolates, the 34 epidemic strains defined by phage typing and by epidemiological data all belonged to one ribotype (ribotype I) representing 56% of the strains belonging to this ribotype. These same 34 epidemic strains were also grouped by REA and MEE typing in a unique profile (REA-A) and MEE electrotype (ET 1). Twenty-two Listeria monocytogenes strains of serogroup 1/2 analyzed by rDNA typing showed nine distinct ribotypes. For the 96 Listeria monocytogenes 4b strains studied, the discriminatory index was highest for phage typing and for any combination including phage typing. Ribotyping appears to be a well reproducible molecular typing method and could be a useful complement to other typing methods for the epidemiological study of listeriosis. PMID- 8508815 TI - Cefdinir-induced modification of the susceptibility of bacteria to the antibacterial activity of human serum and polymorphonuclear neutrophils. AB - The effect of serum on the bactericidal activity of cefdinir, and the ability of the antibiotic to modify the interaction of bacteria with human polymorphonuclear neutrophils were assessed. In the presence of antibiotic, serum-resistant Escherichia coli were sensitised to the bactericidal activity of normal human serum. Cefdinir enhanced opsonophagocytic killing of Escherichia coli and Staphylococcus aureus at suprainhibitory concentrations. Significant potentiation of killing occurred with the combination of inhibitory concentrations of cefdinir, neutrophils and sub-optimal levels of serum opsonins. Pre-exposure of Escherichia coli, but not Staphylococcus aureus, to cefdinir enhanced phagocytic uptake and killing of the antibiotic-damaged bacteria. These results indicate that cefdinir-mediated phenotypic modification of Escherichia coli renders the bacteria susceptible to serum antibacterial activity and phagocytic uptake and intracellular killing. PMID- 8508816 TI - Changes in circulating immune complexes during the Jarisch Herxheimer reaction in secondary syphilis. AB - A cohort of 16 patients with early secondary syphilis were recruited to investigate the role of circulating immune complexes in the pathogenesis of the Jarisch Herxheimer reaction. Eleven of 16 patients had a reaction (68.75%) following initial therapy, characterised by rash potentiation, pyrexia, cardiovascular changes and a number of less specific symptoms. Circulating immune complexes were measured by a standard polyethylene glycol precipitation method and a new sensitive conglutinin binding assay that measured the proportion of IgG, IgM and IgA in complexes, in the first 8 hours after initial therapy. In the latter assay, resting levels of IgG (range 46-700 micrograms/ml) and IgM (range 100-410 micrograms/ml) containing complexes were raised in all patients prior to treatment, but levels were not predictive of those who subsequently had a Jarisch Herxheimer reaction. All patients having a reaction demonstrated a mean fourfold or greater rise in IgG (mean rise 712 micrograms/ml; range 180-1506 micrograms/ml) and IgM (mean rise 804 micrograms/ml; range 200-1120 micrograms/ml) containing complexes between two and eight hours after initial therapy. No such effect was seen in the five patients having no reaction or in a control subject. All these results were confirmed using the polyethylene glycol precipitation method for complex detection. PMID- 8508817 TI - Retrospective review of culture-positive mycobacterial lymphadenitis cases in children in Nottingham, 1979-1990. AB - Laboratory records were reviewed retrospectively for culture-positive cases of mycobacterial lymphadenitis in children less than 15 years old. There were six cases of Mycobacterium tuberculosis infection, and 15 cases of infection with other mycobacteria. There were no clinical features to distinguish tuberculous from non-tuberculous cases. All cases managed by chest physicians were initially treated as tuberculosis, whereas paediatric specialists were likely to use initial management appropriate to the infecting organism. Methods of improving the initial management of non-tuberculous infections are discussed. PMID- 8508818 TI - Lack of evidence of a relationship between genital symptoms, cervicitis and salpingitis and different serovars of Chlamydia trachomatis. AB - Isolates of Chlamydia trachomatis from 424 women were serotyped, and signs and symptoms related to the infecting serovar. Symptoms suggesting genital chlamydial infection were present in 37% of the women, while 15% had clinical findings consistent with lower genital tract infection or ascending infection. Cervicitis, adnexal tenderness and salpingitis were not associated with any specific serovar. On the contrary, the various clinical manifestations tended to occur at similar rates with the different serovars, suggesting a similar pathogenic potential of the serovars detected. PMID- 8508819 TI - Nontyphoidal, nonparatyphoidal salmonella septicemia in adults. AB - A 12-year review identified 21 patients with nontyphoidal, nonparatyphoidal salmonella septicemia. Eight of the patients had no predisposing factors. Factors identified included malignancy in five, recent surgery in four, alcoholism with aspiration pneumonia in two, chronic lung disease in two, diabetes in two, systemic lupus erythematosus in one and burns in one. Ten patients presented with gastroenteritis, two with localized abscesses, two with aspiration pneumonia and the remainder with nonspecific septicemia. Three patients died of underlying diseases and three died shortly after the septicemia of related causes. Six cases were nosocomial infection and were not related to hospital outbreaks. Salmonella septicemia with these serotypes is uncommon (1 per 14,000 admissions, 1 per 4000 blood cultures) and can occur in patients without diminished host resistance. PMID- 8508820 TI - Cefotiam concentrations in the sinus fluid of patients with chronic sinusitis after administration of cefotiam hexetil. AB - Cefotiam hexetil is a prodrug of cefotiam. The concentrations of cefotiam in plasma and sinus secretions were determined in 18 patients (10 males, 8 females, aged 39.3 +/- 13.0 years) with chronic sinusitis. All patients received two 200 mg oral doses of cefotiam hexetil 12 h apart and were divided into four groups according to the time which elapsed between the last dose and collection of secretion samples. The last dose was given 2 h (group I), 3 h (group II), 4 h (group III) or 6 h (group IV) before sinus puncture. Cefotiam concentrations were measured by high-pressure liquid chromatography and microbiological assay, results being very similar with both methods. Mean concentrations of cefotiam with the standard deviation in sinus exudates were 1.04 +/- 0.60 mg/l at 2 h (n = 6), 1.04 +/- 0.33 mg/l at 3 h (n = 4), 0.75 +/- 0.74 mg/l at 4 h (n = 4) and < 0.10 mg/l at 6 h (n = 4). Mean sinus fluid concentrations were higher than mean plasma concentrations in all groups. These results suggest that cefotiam concentrations higher than the MICs for common pathogens are found in sinus secretions up to 4 h after oral administration of cefotiam hexetil. PMID- 8508821 TI - An improved antiserum agar method for detecting carriage of Haemophilus influenzae type b. AB - Enriched Columbia medium was tested against Levinthal medium for the isolation of Haemophilus influenzae type b. In both media, Haemophilus influenzae type b recovery and antigen-antibody precipitation halos were equivalent. Haemophilus influenzae type b colony size and iridescence were superior on enriched Columbia medium. Enriched Columbia medium is inexpensive, simply prepared and easily standardised. PMID- 8508822 TI - Antigen detection in oropharyngeal secretions for rapid diagnosis of pneumococcal pneumonia. AB - To determine the value of detection of antigen in the oropharynx in the diagnosis of pneumococcal pneumonia, oropharyngeal secretions were cultured for the presence of Streptococcus pneumoniae and tested for the presence of pneumococcal antigen. Sputum (if available) collected on the same day was also investigated for the presence of antigen. Detection of pneumococcal antigen was found to be directly related to the severity of pneumococcal carriership or infection (p < 0.0001) and was not related to culture results. Patients with pneumococcal pneumonia had the highest antigen detection rate (38%), followed by patients with pneumonia of unknown etiology (32%) and patients with an acute lower respiratory tract infection due to Streptococcus pneumoniae (20%). Pneumococcal carriers had a detection rate of only 9%. Antigen could be detected in only one patient of the control groups. Although antigen detection in sputum was superior to that in oropharyngeal secretions, concordant results were obtained in 8 (40%) and 6 (36%) patients with pneumococcal pneumonia and pneumonia of unknown etiology respectively. The results strongly suggest that pneumococcal carriage seldom leads to a detectable level of antigen, and that antigen detection in the oropharynx appears to be of additive value in the diagnosis of pneumococcal pneumonia. PMID- 8508823 TI - Meningitis and sepsis due to group G streptococcus. PMID- 8508824 TI - 'Streptococcus milleri' septicemia in a patient with colorectal carcinoma. PMID- 8508825 TI - Iron, trauma and infection. PMID- 8508826 TI - Isolation of verotoxin-producing Escherichia coli from slaughtered pigs. PMID- 8508827 TI - Penicillin susceptibility testing of Lancefield group C and G streptococci by the modified stokes method. PMID- 8508828 TI - Methadone diluted with contaminated orange juice or raspberry syrup as a potential source of disseminated candidiasis in drug abusers. PMID- 8508829 TI - Tuberous sclerosis: CT and MRI characteristics. AB - Tuberous sclerosis is a disease characterized by the presence of hamartomatous nodules in various organs, including the brain. Thirteen CT scans and four MR investigations were performed in 13 patients. CT is superior to MR in demonstrating the presence of subependymal nodules, thereby confirming or establishing the diagnosis of tuberous sclerosis. MR is superior to CT in demonstrating the peripheral lesions, which are characterized by a long T2 relaxation time. Differentiation between cortical tubers and subcortical lesions is not yet accurate. PMID- 8508830 TI - MRI of a large disappearing intramedullary space-occupying lesion in a 12-year old female: case report. PMID- 8508831 TI - Simultaneous supra- and infratentorial chronic subdural hematoma. PMID- 8508832 TI - Late CT-findings in non-surgically treated lumbar disc herniations. AB - Eighteen patients with non-surgically treated lumbar disc herniation underwent follow-up CT examination at an average of 5.2 years (range 4.3-6.1 years) after their initial examination. In 12 of the patients disc herniation had resolved, although only five of these patients had complete relief of symptoms. Although disc herniation has a tendency to heal spontaneously, there is poor correlation between the morphological changes and the relief of pain. PMID- 8508833 TI - Evaluation of gracilis muscle transposition for fecal incontinence with magnetic resonance imaging. AB - Ten consecutive patients with incapacitating fecal incontinence were treated with 'anal dynamic graciloplasty' (transposition of the gracilis muscle around the anal canal and implantation of intramuscular electrodes connected with an implanted pulse generator, 6 weeks later) to achieve continence. We measured the gracilis muscle diameter immediately after transposition and before implantation of the stimulation device. It was found that gracilis diameter decreased from 12 (5 days after transposition) to 8 mm, 6 weeks later (mean decrease: 4 mm (95% confidence interval 3.6), n = 10, P < 0.05). In addition, morphology demonstrated a decrease of both Type I and Type II muscle fiber diameter and an increase in endomysial collagen. Despite this decrease in muscle (and muscle fiber) diameter, electrical stimulation of the transposed gracilis muscle increased the pressure into the anal canal from 37 to 55 mmHg (mean increase: 17 mmHg (95% confidence interval 6.29), P < 0.05). Fecal continence was achieved in seven (70%) of these patients. Further analysis revealed no correlations between reduction of the gracilis muscle diameter before implantation of the stimulation device and clinical outcome in terms of achieved continence and/or anal canal pressures. MRI is an excellent method to demonstrate the shape of gracilis muscle after transposition. However, the size of transposed gracilis muscle is not associated with the functional outcome. PMID- 8508834 TI - Malignant anorectal melanoma: usefulness of fat saturation MR imaging. PMID- 8508835 TI - Rectal carcinoid tumor: endoscopic ultrasonographic detection and endoscopic removal. AB - Eight patients with rectal carcinoid tumors were examined by endoscopic ultrasonography (EUS) to assess the depth of invasion of the rectal wall. All resected tumors were contained within the submucosa and their depth of invasion was correctly diagnosed by EUS before treatment. Perirectal lymph nodes were not delineated by EUS. Four patients who were treated only with endoscopic polypectomy were completely cured as were four patients who had a surgical resection. EUS is useful in selecting the candidates for endoscopic removal or local resection and thus may help to avoid unnecessary radical surgery. PMID- 8508836 TI - Magnetic resonance imaging of peliosis hepatis: a case report. PMID- 8508837 TI - Primary lymphoma of the liver: MR findings. AB - Primary lymphoma of the liver is a rare disease. The MR appearances of three cases of pathologically confirmed primary non-Hodgkin's lymphoma of the liver are presented. All three lymphomatous lesions appeared as unique well demarcated focal liver lesions on MR images. On T1-weighted images, two lesions were hypointense and one slightly hyperintense to the liver. On T2-weighted images, the three lesions were slightly heterogeneous and hyperintense. Lobulation, which was better seen on T2-weighted images, was noticed in one lesion. One lesion was studied after gadopentetate dimeglumine injection and showed marked and heterogeneous enhancement. PMID- 8508838 TI - Aorto-enteric fistula: unusual CT appearance. PMID- 8508839 TI - Ultrasonographic features of type B Niemann-Pick disease. PMID- 8508840 TI - Chest radiographic findings in childhood lipoid pneumonia following aspiration of animal fat. AB - The pulmonary radiological manifestations of lipoid pneumonia following a cultural practice of forced feeding of rendered animal fat (ghee) in 24 Saudi children are described. The age range is 15 days to 11 years with 68% of cases being in infancy. The chest radiographic appearances encountered could be grouped into four broad patterns, viz, bilateral multilobar consolidations (BMLC) in 50% (12 cases), bilateral perihilar infiltrates (BPHI) with or without associated lobar consolidation in 21% (five cases), right perihilar infiltrates (RPHI) in 21% (five cases) and unilateral right multilobar consolidation (RMLC) 8% (two cases). The pneumoniae were non-resolving acute or chronic lung consolidations despite the usual antimicrobial chemotherapy. Associated nodular dense opacities (granulomas) were seen in the lower lobes of four of the 12 cases in the first group. Complications, seen also in this first group, included chronic collapse consolidation, fibrosis and death in three cases. In communities where the traditional practice of infant feeding with ghee exists, these pulmonary radiological patterns, although in some cases indistinguishable from those of bacterial pneumoniae, should raise the suspicion of ghee administration with consequent early diagnosis and energetic management to avert prolonged morbidity and potential death. PMID- 8508841 TI - Ultrasound, CT and MR findings in a case of renal angiomyoma. PMID- 8508842 TI - Evaluation of tumor blood perfusion by dynamic MRI and CT in patients undergoing thermoradiotherapy. AB - In 18 patients who were treated with combined regional hyperthermia and radiation for recurrent pelvic tumors, blood flow related data were obtained using dynamic computed tomography and dynamic magnetic resonance imaging. The enhancement of contrast material (delta HU) and Gadolinium DTPA (delta SI) over baseline in the early phase (15-30 s) after bolus injection is dependent upon perfusion. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery. With regard to the mean perfusion values we are able to separate high, medium and low perfused pelvic tumors. Flow rates expressed as delta HU for dynamic CT and delta SI for dynamic MRI show a significant inverse correlation with the achieved steady state temperatures above baseline. Values of enhancement of contrast material higher than 15-35 delta HU or 300-700 delta SI indicate flow rates which were limiting in achieving steady state temperatures higher than 3 degrees C above baseline (core temperature). PMID- 8508843 TI - Magnetic resonance imaging findings in aggressive fibromatosis. PMID- 8508844 TI - The double-line sign of osteonecrosis: evaluation on chemical shift MR images. AB - The MR appearance of osteonecrosis was assessed on selective fat and water images to further evaluate the features of the double-line sign of osteonecrosis. Conventional T1- and T2-weighted spin-echo and frequency selective chemical shift images of eight patients with avascular necrosis of the femoral head and three patients with bone infarcts were retrospectively reviewed. Eight of 11 patients showed a double-line sign on T2-weighted spin-echo images. In these cases correlation with selective water images revealed that a chemical shift artifact contributed to the appearance and location of the hyperintense line. The double line sign was not seen in three patients with radiologically and clinically proven osteonecrosis. It is concluded that chemical shift imaging improves our understanding of the nature of the double-line sign. PMID- 8508845 TI - Spurious thyroid cancer bone metastases on radioiodine scan due to external contamination. AB - In patients with differentiated thyroid cancer, bone uptake on radioiodine whole body scan indicates functional metastasis and is usually followed by treatment with a high dose of 131I. However, apparent radioiodine uptake in the bone may be due to other causes. We describe 19 radioiodine artifacts that mimicked bone metastases and were proven to be due to external contamination as they disappeared on reimaging after skin cleaning and garment change (15 artifacts) or on a repeat study (four artifacts). All artifacts were noted only on anterior views; 12 in the skull, five in the shoulder girdle and two in the upper extremity. Thirteen artifacts were focal and six were smeared. The prevalence of scans showing such artifacts was 0.5% of the total number of radioiodine scans performed over a 3-year period. Distinguishing contamination artifacts from real bone metastases based on scintigraphic appearance is rather difficult. Repeat post-cleaning images should be obtained in all newly identified cases of apparent bone metastasis. PMID- 8508846 TI - The frequency of technical errors in an automatic daylight system. AB - Considerable interest has been devoted to automatic daylight film processing systems (ADS) because of their potentials in saving money by decreasing the need for dark-room personnel. In 1982 a new centralized department of diagnostic radiology became operational at Haukeland University Hospital, and six ADS were installed 1983-1984. After 4 years in use the ADSs have been found reliable with few technical errors. PMID- 8508847 TI - Automatic film processors' quality control test in Greek military hospitals. AB - The two major military radiology installations (Athens, Greece) using a total of 15 automatic film processors were assessed using the 21-step-wedge method. The results of quality control in all these processors are presented. The parameters measured under actual working conditions were base and fog, contrast and speed. Base and fog as well as speed displayed large variations with average values generally higher than acceptable, whilst contrast displayed greater stability. Developer temperature was measured daily during the test and was found to be outside the film manufacturers' recommended limits in nine of the 15 processors. In only one processor did film passing time vary on an every day basis and this was due to maloperation. Developer pH test was not part of the daily monitoring service being performed every 5 days for each film processor and found to be in the range 9-12; 10 of the 15 processors presented pH values outside the limits specified by the film manufacturers. PMID- 8508848 TI - Orthopantography of the wrist and the knee. AB - Initial experience with panoramic radiography of the wrist and the knee is presented. The technique offers potential new evaluation of these joints. A standard PA projection demonstrates the carpal bones with almost no superimposition. Additional projections permit more detailed demonstration of the scaphoid and wrist compartments. Similar panoramic studies of the normal knee demonstrated alternative images of the patella, the femoral condyles and tibial plateau. Orthopantography of the joints may provide additional information in the diagnosis of joints abnormalities. PMID- 8508849 TI - National cholesterol policies. PMID- 8508850 TI - Prevalence of coronary heart disease in Icelandic men 1968-1986. The Reykjavik Study. AB - The prevalence of coronary heart disease (CHD) was determined in a general population sample of 9141 Icelandic men aged 34-79 years, and the prevalence of four different forms of CHD was estimated separately: symptomatic infarction fulfilling WHO-MONICA criteria for definite myocardial infarction; myocardial infarction detected by ECG changes only (unrecognized, silent infarction); angina pectoris detected by the Rose questionnaire and associated with ECG manifestations of myocardial ischaemia, either at rest or during exercise, but no manifestations of myocardial infarction; angina pectoris without ECG changes indicative of myocardial ischaemia. The study was conducted in five stages allowing evaluation of trends from 1968-1986. Age was a major determinant of the prevalence of all forms of CHD. Thus, the prevalence of myocardial infarction (symptomatic or silent) rose from undetectable levels in the youngest age group (30-34 years) to around 12% (7% symptomatic and 5% silent) in the oldest group (75-79 years) and the prevalence of all forms of CHD rose from 4% in the youngest age group to 23% in the age group 70-74 years. Age-standardized comparison was carried out on the prevalence of the different forms of CHD at different stages of the study in 50-64-year-old men who were represented in all stages of the study. There was a gradual increase in the prevalence of myocardial infarction from 3% (symptomatic and silent combined, CI 1.9-4.8) in 1968 to 4.9% in 1986 (CI 3.9-6.1) (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508851 TI - Heart volume and cardiovascular mortality. A 16 year follow-up study of 1984 healthy middle-aged men. AB - The possible association between heart size measured during a cardiovascular screening examination and cardiovascular mortality was studied in 1984 healthy men aged 40-59 years. At the 16-year follow-up 278 had died, 150 from cardiovascular diseases. Cardiovascular mortality was 2.2 times higher among the 122 men with heart size > or = 500 ml.m-2 than among those with heart size < 500 ml.m-2. This association was, however, exclusively confined to men with physical fitness below median in whom the corresponding mortality ratio was 4.6 (95% confidence interval 2.5-8.4; P < 0.001) after adjustment for age, smoking, cholesterol, blood pressure and heart rate. Heart size measurements from routine chest X-rays is fast, easy, inexpensive and appears to provide valuable, independent screening information in healthy, middle-aged men. PMID- 8508853 TI - When should we diagnose incomplete right bundle branch block? AB - An rSr' pattern with QRS duration of less than 0.12 s in the right precordial leads can be due to incomplete right bundle branch block (which may progress to complete right bundle branch block) or can be a normal electrophysiological variant. To identify other ECG features that may help to distinguish between these two possibilities, ECGs of 15 patients who progressed from normal to complete right bundle branch block through an intermediate rSr' pattern of incomplete right bundle branch block were analysed. The following features in the right precordial leads (V1, V2) that preceded or accompanied the appearance of the rSr' were identified: diminution of the S wave depth (100%), inversion of ratio of the S wave depth to SV1 > SV2 (93%), slurring of the downstroke or upstroke of the S wave (27%) and prolongation of the QRS duration to > or = 0.10 s (73%). When a further 79 subjects with rSr' pattern in the right precordial leads and QRS duration of < 0.12 s were divided into those with SV1/SV2 ratio > 1.0 and those with SV1/SV2 < 1.0, compared with the latter the subjects with SV1/SV2 ratio > 1.0 were found to be significantly older (59.8 +/- 18.4 years vs 32.8 +/- 18.1 years, P < 0.001), to exclusively show S wave slurring (37% vs 0%), and to more likely have a QRS duration > or = 0.10 s (74% vs 7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508852 TI - The relationship between blood viscosity and blood pressure in a random sample of the population aged 55 to 74 years. AB - Blood viscosity is elevated in hypertensive subjects, but the association of viscosity with arterial blood pressure in the general population, and the influence of social, lifestyle and disease characteristics on this association, are not established. In the Edinburgh Artery Study, 1592 men and women aged 55-74 years selected randomly from the general population attended a university clinic. A fasting blood sample was taken for the measurement of blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen). Systolic pressure was related univariately to blood viscosity (P < 0.001), plasma viscosity (P < 0.001) and plasma fibrinogen (P < 0.01), but the association with fibrinogen did not persist after adjusting for body mass index. Diastolic pressure was related univariately to blood viscosity (P < 0.001) and plasma viscosity (P < 0.001) and haematocrit (P < 0.001) but not to fibrinogen. The only difference between the sexes was that the association between blood viscosity and systolic pressure was confined to males. Blood viscosity was associated equally with systolic and diastolic pressures in males, and remained independently related on multivariate analysis adjusting for age, sex, body mass index, social class, smoking, alcohol intake, exercise, angina, HDL and non-HDL cholesterol, diabetes mellitus, plasma viscosity, fibrinogen, and haematocrit. PMID- 8508854 TI - Short-term effects of atrial versus atrio-ventricular pacing on myocardial ischaemia in coronary artery disease patients. AB - This investigation was undertaken to evaluate the effects of short-term atrial vs atrio-ventricular pacing on myocardial ischaemia. The study was in two parts. In part one, 12 coronary artery disease patients were studied to investigate the effects of the two pacing modes on angina pectoris, coronary sinus O2 saturation and lactate. The two pacing modes were each applied for 5 min at 25 beats.min-1 more than the maximum heart rate of the exercise test. Coronary sinus O2 saturation and lactate were estimated before and after pacing. In part two, 13 patients with left anterior descending coronary artery disease were studied to investigate the effects of the two pacing modes on coronary flow reserve, using a Doppler catheter in the above mentioned branch after the administration of 10 mg intracoronary papaverine. The pacing rate was 15 beats.min-1 greater than the resting heart rate. Coronary sinus lactate and O2 saturation changes were the same and angina pectoris developed at about the same time from the beginning of pacing under both modes. Coronary flow reserve was 2.1 +/- 0.7 during atrial pacing and 2.1 +/- 1.1 during atrio-ventricular pacing (ns). It is concluded that short-term atrial and atrio-ventricular pacing have the same effects on myocardial ischaemia in coronary artery disease patients. PMID- 8508855 TI - A standardized finger cooling test for Raynaud's phenomenon: diagnostic value and sex differences. AB - In 99 patients with primary Raynaud's phenomenon (RP), in 97 with secondary RP and in 101 healthy subjects, finger skin temperature and laser Doppler flux were measured before, during and after immersion of the hand in a 16 degrees C water bath. We determined the baseline value, the values at the end of the cooling period and after 12 and 20 min of recovery, the percentual decrease during cooling and the mean values during cooling, during recovery and during the whole test. Most of the finger skin temperature and laser Doppler flux parameters were significantly lower in females than in males in all three groups. There were no significant differences between patients with either primary or secondary RP. In both sexes, all test parameters (with the exception of the percentual decrease during cooling) were significantly lower in the patients with RP than in healthy subjects. With a diagnostic specificity of 70%, the sensitivity varied between 55% and 81% for the different test parameters. Although, in both sexes, finger skin temperature and laser Doppler flux values before, during and after cooling were significantly lower in patients with RP than in healthy subjects, the considerable overlap between both groups limits the diagnostic value in individual cases. PMID- 8508856 TI - Return to work following coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. AB - Return to work (RTW) and other treatment outcomes of coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) patients were compared. Consecutive patients at one centre (n = 112 CABG and 119 PTCA patients) were interviewed 6-18 months following treatment (groups were similar in sex and social class). Pre-treatment employment levels were similar (41 and 38% for CABG and PTCA groups, respectively). PTCA patients were more likely to smoke, have angina, have less advanced cardiovascular disease and have been advised to stop working for medical reasons pre-treatment. Post-treatment levels of employment increased significantly. RTW rates were similar for CABG and PTCA groups (59 and 68% respectively). Both groups had reduced smoking to similar levels. The PTCA group continued to have higher levels of angina. For those without angina, PTCA patients were significantly more likely to return to work (73 vs 55%, P < 0.01). Both CABG and PTCA resulted in increased employment post-treatment. PMID- 8508857 TI - Early diagnosis of subacute free wall rupture complicating acute myocardial infarction. AB - Of 2608 consecutive patients with acute myocardial infarction, 24 developed subacute free wall rupture (= 0.92%; 95% C.I. = 0.6-1.4). Clinical manifestations varied widely (shock on admission; 25% of cases; severe arrhythmias followed by shock: 17%; shock during hospital stay: 42%; symptoms suggestive of infarct extension without shock: 17%). The electrocardiograms were confusing rather than revealing: 56% of patients showed new ST segment elevations of 0.2 to 1 mV in the infarct-related leads, while autopsy or creatinine phosphokinase evidence of infarct extension was missing. In the first 21 cases, therefore, no definitive diagnosis was made before autopsy. Using 197 infarct patients in cardiogenic shock or with infarct extension during the acute stage, i.e. a patient group with comparable clinical manifestations, as control group, a logistic regression model was generated in which the variables age, lateral wall involvement and history of hypertension were used for estimating the probability of subacute rupture. In fact, probability may rise to more than 40% in major subgroups. As death occurred after a median interval of 8 h (45 min-6.5 weeks) following the onset of rupture symptoms, echocardiography must be performed urgently in all cases presenting symptoms of shock or infarct extension. Pretest probability which can be roughly estimated from our model as well as sensitivity and specificity of individual echocardiographic or clinical parameters are indispensable for correct therapeutic decisions. The routine application of this algorithm in our department contributed to a timely diagnosis in the last three consecutive cases of whom one patient survived. PMID- 8508858 TI - The sinus node function: normal and pathological. AB - To determine the evolution with age, of extrinsic and intrinsic sinus node electrophysiological parameters and to assess the role of each component of the autonomic nervous system relative to age in patients with and without sick sinus syndrome, electrophysiological studies of sinus node function were performed in 223 patients subdivided into four groups according to the results of their electrophysiological testings: group I included patients with normal extrinsic and intrinsic sinus node function, group II patients with exclusive extrinsic sinus dysfunction, group III patients with exclusive intrinsic sinus dysfunction and group IV patients with extrinsic and intrinsic sinus node dysfunction. The electrophysiological study was performed twice: at basal state and after autonomic blockade. Whatever the sinus node function (normal or abnormal) the extrinsic sinus node electrophysiological variables did not correlate with age; inversely all the electrophysiological measurements of the intrinsic sinus node (normal or abnormal) lengthened progressively with age, suggesting an ageing phenomenon of the intrinsic sinus node throughout life. Moreover, the study of the percentage of chronotropy of the sinus node electrophysiological variables shows a predominance of vagal tone in young subjects, whereas sympathetic activity is most prominent in elderly patients with and without sick sinus syndrome. The sinus node (normal or pathological) represents an equilibrated system: the age-related modification of the autonomic nervous system counterbalances the senescence of the intrinsic sinus node in such a way that the basal electrophysiological characteristics remain stable throughout life. PMID- 8508859 TI - Effect of altered loading conditions during haemodialysis on left ventricular filling pattern. AB - Changes in the circulating volume associated with haemodialysis result in modification of left ventricular loading conditions. To determine the influence of haemodialysis on Doppler indices of left ventricular filling, 12 patients (mean age 40.8 +/- 2.7 (SEM) years) with renal insufficiency but without overt heart disease were studied by Doppler-echocardiography immediately before and after haemodialysis. Haemodialysis resulted in a decrease in body weight from 68.0 +/- 3.8 kg to 65.0 +/- 3.7 kg (P < 0.01). Heart rate and blood pressure did not change significantly during haemodialysis. Left ventricular diastolic dimension (M-mode) decreased from 53.5 +/- 1.1 mm to 49.5 +/- 1.9 mm (P < 0.05), whereas the shortening fraction did not change. Haemodialysis elicited marked changes in the early diastolic rapid filling wave (E wave) recorded by pulsed Doppler at the level of the mitral annulus. Peak velocity of the early rapid filling phase (peak E) decreased significantly from 95.3 +/- 8.2 cm.s-1 to 63.0 +/- 5.7 cm.s-1 (P < 0.001) and mid-diastolic deceleration of transmitral velocity decreased from 437.3 +/- 54.2 cm.s-2 to 239.7 +/- 54.4 cm.s-2 (P < 0.01). The peak filling velocity during atrial contraction (peak A) did not change (79.7 +/- 6.3 cm.s-1 vs 74.1 +/- 4.7 cm.s-1; P = NS). The ratio peak E/peak A decreased from 1.19 +/- 0.06 to 0.85 +/- 0.04 (P < 0.01) during haemodialysis. The results provide further evidence for the pronounced preload-dependence of Doppler indices of left ventricular diastolic function. PMID- 8508860 TI - Discrepancy between systolic and diastolic dysfunction of the left ventricle in patients with Duchenne muscular dystrophy. AB - To assess the systolic and diastolic dysfunction of the left ventricle (LV) in relation to age and the severity of impairment in Duchenne muscular dystrophy (DMD), we performed M-mode, two-dimensional and pulsed-wave Doppler echocardiography in 45 male subjects with DMD aged 8 to 25 years and in 40 age matched healthy controls. Systolic dysfunction started in the first decade of life, with some patients showing severe systolic dysfunction in their early teens. This dysfunction, however, did not always depend on the severity of the skeletal muscle disease. No patients with DMD showed an increase in peak atrial velocity and time-velocity integrals of the atrial contraction velocity curve, findings frequently reported to precede the abnormalities in many cardiac diseases; it was thought therefore that these patients had no increase in left atrial compensation. Diastolic dysfunction may not routinely precede or accompany the systolic dysfunction in DMD, in contrast with what is reported in patients with ischaemic or hypertensive heart disease. DMD patients usually show a predominant systolic dysfunction. PMID- 8508861 TI - Release of atrial natriuretic peptide in relation to metabolic changes during myocardial ischaemia induced by coronary angioplasty. AB - The inter-relationships between ischaemia-induced metabolic changes and atrial natriuretic peptide (ANP) release were studied in 18 patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA). Transcardiac differences in ANP, lactate, pH, pCO2 and O2 saturation were analysed before and after balloon inflation. The patients were divided into ischaemia and non-ischaemia groups on the basis of the change in lactate extraction ratio during balloon inflation. The ischaemia group (patients with a decrease in lactate extraction ratio) showed an increase of 27 +/- 15 pg.ml-1 in the transcardiac ANP difference, whereas a decrease of 27 +/- 17 pg.ml-1 occurred in the non-ischaemia group (no decrease in lactate extraction ratio). The change between the two patient groups was statistically significant (P < 0.05). Metabolic 'pre conditioning' was not observed in patients with successive dilatations, therefore data from all the dilatations were combined and evaluated by regression analysis. A correlation coefficient of 0.40 (P < 0.05) was obtained between the PTCA induced changes in transcardiac ANP and lactate differences. We conclude that transient myocardial ischaemia induced by PTCA increases circulating ANP concentrations in patients with signs of metabolic ischaemia, but not in those without. PMID- 8508862 TI - Sphingomyelin biosynthesis and efflux correlates with cholesterol metabolism and is higher in vascular endothelial cells than in smooth muscle cells. AB - We compared the metabolism of cellular phospholipids in bovine aortic endothelial and smooth muscle cells in culture. [3H]Choline was incorporated in both cell types into phosphatidylcholine (86-90%) and sphingomyelin (10-14%). Endothelial cells demonstrated preferential efflux of sphingomyelin which represented 22.5% of the radiolabelled phospholipids in the incubation medium while in smooth muscle cells it represented 10%, so that after 7 days, the sphingomyelin in the medium represented 40% and 16% of total synthesized sphingomyelin in endothelial and smooth muscle cells, respectively. Incorporation of [3H]choline by endothelial and smooth muscle cells was reduced in the presence of serum, but not in the presence of lipoprotein deficient serum, indicating that cells can acquire phosphatidylcholine and sphingomyelin from lipoproteins. Lipoproteins were shown also to support the efflux of cellular radiolabelled phospholipids from both cell types, but at a higher degree from endothelial cells than from smooth muscle cells. Exposure of these cultures to cholesterol rich serum increased the synthesis of phosphatidylcholine, and to a higher extent of sphingomyelin, with concomitant decrease in the efflux of these two phospholipids. These results demonstrate the role of cholesterol in the regulation of phosphatidylcholine and sphingomyelin biosynthesis and efflux in vascular cells. Furthermore, the higher efflux of sphingomyelin in endothelial cells than in smooth muscle cells may support the extensive efflux of cholesterol observed in endothelial cells and indicate biochemical differences in lipid metabolism between vascular endothelial and smooth muscle cells. PMID- 8508863 TI - Angiotensin converting enzyme inhibition at rest and during exercise in congestive heart failure. AB - The haemodynamic effects of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, were studied in patients in New York Heart Association functional class II and III. Twenty-one clinically stable patients with coronary artery disease or cardiomyopathy completed a randomized double blind treatment period of 2 months with either 15 mg zofenopril once daily or placebo. Regular therapy with digoxin and diuretic drugs was continued. Left ventricular volumes were measured by radionuclide angiography at rest and during submaximal bicycle exercise. Zofenopril significantly increased mean stroke volume at rest from 59 to 67 ml (48 vs 48 ml in the control group, 95% confidence interval of the difference 1 to 16 ml) and left ventricular ejection fraction at rest from 39 to 43% (30 vs 30% in the control group, 95% confidence interval of the difference 1 to 8%). No significant changes occurred in heart rate, cardiac output, and blood pressure at rest, and zofenopril did not result in haemodynamic alterations during exercise. Thus, 15 mg of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, administered once daily to patients with moderate heart failure increases left ventricular function at rest, but not during exercise. PMID- 8508864 TI - Intravenous enoximone or dobutamine for severe heart failure after acute myocardial infarction: a randomized double-blind trial. AB - Intravenous infusions of enoximone or dobutamine were given, using a double dummy technique, in a randomized, double-blind study, to 18 patients with acute myocardial infarction who had persisting signs of left ventricular failure after treatment with intravenous diuretics. Blood pressure, heart rate and cardiac output, by transcutaneous Doppler aortovelography, were measured and any arrhythmias recorded by Holter monitoring. Eight of the nine enoximone treated patients showed clinical improvement. One patient in the enoximone group failed to respond and subsequently died. Five of the nine dobutamine treated patients showed clinical improvement. The other four patients in the dobutamine group experienced tachyarrhythmias and were withdrawn from the study; one of these patients also deteriorated and died. There were no significant differences in systolic or diastolic blood pressure either within or between the two treatment groups during the study. Enoximone increased cardiac output by 32% (P = 0.003), and dobutamine by 46% (P < 0.001); there was no significant difference between groups. Dobutamine also significantly increased heart rate from a mean of 108 beats.min-1 to 117 beats.min-1 (P < 0.001). There was no difference between the two groups in ventricular ectopic counts, but dobutamine produced significantly more runs of supraventricular and ventricular tachycardia (P = 0.0003). Enoximone was better tolerated with fewer side-effects than dobutamine in doses which produced similar increases in cardiac output. In the setting of an acute myocardial infarction when inotropic therapy is indicated, enoximone is a better choice than dobutamine. PMID- 8508865 TI - Effective pulmonary capillary pressure in experimental myocardial ischaemia. AB - Effective pulmonary capillary pressure and extravascular lung water were investigated in dogs (n = 9) with normal heart function and after development of acute myocardial ischaemia. During control, no impairment of cardiopulmonary performance was observed. Extravascular lung water was in the normal range (8.1 +/- 2.8 ml.kg-1) and the effective pulmonary capillary pressure accounted for 1.36 +/- 0.53 kPa (10.2 +/- 4 mmHg). No correlation between extravascular lung water and effective pulmonary capillary pressure was observed (r2 = 0.347, P = 0.06). Arterial (RPA) and venous pulmonary resistance (RPV) were 70 +/- 15% and 30 +/- 6%, respectively. Acute myocardial ischaemia was induced by one stage occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, heart rate and left ventricular end-diastolic pressure. Oxygenation deteriorated, but no hypoxaemia occurred in any animal and CO2 elimination remained unchanged. Extravascular lung water was elevated (16.5 +/- 7.9 ml.kg-1, P < or = 0.01), and effective pulmonary capillary pressure was higher when compared with the control state (2.32 +/- 1.05 kPa (17.4 +/- 7.9 mmHg), P < or = 0.01). There was a significant correlation between both parameters (r2 = 0.528, P < or = 0.05). Longitudinal distribution of pulmonary vascular resistance was altered, and RPA decreased to 60 +/- 13% (P < or = 0.05), while RPV increased to 40 +/- 8% (P < or = 0.05). It is concluded that development of lung oedema is related to elevated effective pulmonary capillary pressure in dogs with acute myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508866 TI - Changes in canine ventricular fibrillation threshold induced by verapamil, flecainide and bretylium. AB - The changes produced by verapamil, bretylium and flecainide in both ventricular fibrillation threshold (VFT) and ventricular repetitive response threshold (VRRT) were studied in 20 closed-chest dogs anaesthetized with pentobarbital. Right ventricle endocardium thresholds were determined using bipolar electrode catheters. Increasing intensity stimulus trains (200 ms, 4 ms, 100 Hz, 1 mA steps) were delivered 50 ms after QRS; VRRT and VFT were calculated before and after drug administration. Three study groups were considered according to the drug assayed: (1) verapamil 0.15 mg.kg-1 n = 6; (2) flecainide 2.0 mg.kg-1 n = 7, and (3) bretylium 10.0 mg.kg-1 n = 7. Flecainide significantly increased VRRT (4.8 +/- 1.4 vs 9.4 +/- 1.5 mA, P < 0.05), but the latter failed to change in the other two groups. VFT remained unchanged with verapamil, increased slightly post flecainide (10.3 +/- 4.6 vs 12.4 +/- 4.1, P < 0.05 mA) and markedly post bretylium (10.3 +/- 4.6 vs 17.3 +/- 7.5, P < 0.05). VFT changes were significantly correlated (r = 0.77, P < 0.05) with the effective refractory period changes in the bretylium group. Thus, of the three drugs tested, bretylium induced the greatest VFT increases without modifying VRRT, whereas flecainide affected both parameters. Only in the bretylium series were ERP changes significantly correlated to the corresponding VFT changes. This suggests that ventricular fibrillation threshold increase is not a non-specific property of antiarrhythmic drugs. Changes in ventricular repetitive response threshold may provide additional information. PMID- 8508867 TI - Chronic (or healed) myocarditis mimicking arrhythmogenic right ventricular dysplasia. AB - The aetiology of arrhythmogenic right ventricular dysplasia is still unknown, and there are few reports on familial coincidence in the literature. A case of a previously healthy man with an episode of acute myocarditis is described. After recovery from acute myocarditis, the patient was resuscitated from aborted sudden cardiac death 16 months later. Angiographic and electrophysiological evaluation suggested the pattern of arrhythmogenic right ventricular dysplasia. The case seems to suggest that arrhythmogenic right and/or left ventricular dysplasia could be mimicked by chronic (or healed) myocarditis. PMID- 8508868 TI - Right atrial diverticulum and hypertrophic cardiomyopathy. AB - This report describes the case of a young man with a right atrial diverticulum and hypertrophic cardiomyopathy who died suddenly. The relationship of congenital diverticulosis of the heart with hypertrophic cardiomyopathy is discussed. PMID- 8508869 TI - Control of oral anticoagulant therapy. PMID- 8508870 TI - Perioperative antibiotic prophylaxis in patients undergoing radical surgery for gynecologic cancer: single dose versus multiple dose administration. AB - A prospective, randomized study comparing single dose intravenous antibiotic prophylaxis with multiple-dose regimen in patients undergoing radical surgery for gynecologic malignancy was carried out. The majority of patients had cervical cancer. Thirty-seven patients in group A received one dose of 4 g piperacillin and 800 mg tinidazole 30 minutes before surgery. Twenty-nine patients in group B additionally received 4g piperacillin 8 hours and 4g piperacillin and 800 mg tinidazole 16 hours after the first dose. There were no significant differences between groups A and B with regard to median patient age, performance status, cardiologic and pulmonary status, or frequency of diabetes. There were also no significant differences between either group with regard to the parameters documented postoperatively, such as median hospital stay, leukocyte values, or febrile episodes. Forty-three per cent of patients in group A and 48% of patients in group B had no complications (p > 0.05). Twenty-three per cent of patients in group A and 31% of patients in group B developed infections (p > 0.05), 85% of which occurred in the urinary tract. The data suggest that a single dose of intravenous antibiotics is as effective as multiple dose administration in the perioperative prophylaxis in radical gynecologic surgery. PMID- 8508871 TI - Recurrence of dermatofibrosarcoma protuberans of the vulva. A clinical, histological, and ultrastructural study. AB - Dermatofibrosarcoma Protuberans of the vulva is an extremely rare low grade sarcoma of the dermis. Wide local excision is the recommended treatment while a more radical surgery may be needed in cases of recurrences. Follow up must be prolonged for a long time since tumors may recur even after considerable period. PMID- 8508872 TI - Possible role of goserelin, an LH-RH agonist in the treatment of gynaecological cancers. AB - Twenty-one patients were enrolled in a pilot study in order to evaluate the clinical efficacy of the GnRH analogues in the treatment of hormone dependent gynaecological malignancies. Seven patients with recurrent or advanced endometrial adenocarcinoma and fourteen patients with ovarian carcinoma had a 4 weekly subcutaneous injection in the abdominal wall of 3.6 mg goserelin (Zoladex- ICI Pharmaceuticals). Overall, four of the 21 patients showed regression, nine had their disease stabilised and eight showed progression. No important side effects were noticed. PMID- 8508874 TI - Use of prophylactic antibiotics in patients with carcinoma of the cervix receiving intracavitary radium insertion. AB - The efficacy was studied of prophylactic antibiotics in preventing febrile morbidity in patients with carcinoma of the cervix undergoing intracavitary radium insertions. Of 93 consecutive patients who had completed external irradiation and two intracavitary radium insertions, 63 (67.74%) had fever over 37.5 degrees C and 19 (20.43%) had fever over 38 degrees C during radium insertion when prophylactic antibiotics were not given. When 3 gm cefoxitin was given over 24 hrs in divided doses as prophylaxis, 39 (41.93%) had fever over 37.5 degrees C and 8 (8.60%) had fever over 38 degrees C. The difference was found to be statistically significant for fever over 37.5 degrees C (p < 0.001) and fever over 38 degrees C (p < 0.05). There was no difference in the duration of fever in the two groups, but the use of antibiotic prophylaxis apparently decreased the need for subsequent therapeutic antibiotics from 13.98% to 4.30%. No difference in the febrile incidence was found when considering the size of the cervical tumour, the stage of the disease, or whether it was a first or second radium insertion, or whether the patient had her menopause already. Prophylactic antibiotics were also found to be more effective in preventing febrile morbidity over 37.5 degrees C in those receiving adjuvant chemotherapy as compared to the general study group (p < 0.025). We concluded that the use of prophylactic antibiotics has beneficial effect in decreasing febrile episodes during the period the radium was inserted, as well as in reducing subsequent need for therapeutic antibiotics, while its use in immunocompromised patients who are prone to sepsis may also be of advantage. PMID- 8508873 TI - Neoadjuvant and salvage chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5 FU) in cervical carcinoma. AB - A regime of cis-platin (CDDP) (80 mg/m2) and 5-fluorouracil (5-FU) (1000 mg/m2/day, day 1 to 5) repeated after 21 days, was prospectively analyzed in 12 advanced epidermoid cervical cancers as first treatment, prior to radiotherapy (neoadjuvant chemotherapy), and in 30 cases of progressive, recurrent or metastatic disease after radiotherapy (salvage chemotherapy), in order to evaluate efficacy and toxicity. Among the 10 evaluable neoadjuvant cases we observed 2 complete, 7 partial responders and 1 stabilized. They all achieved a complete response after radiotherapy and 6 remain alive after 18 to 72 months. None of the salvaged patients achieved a complete response and only 26.9% responded partially. Only one case, though fatal, of myelodepression was found in the neoadjuvant group. Conversely, 70% of salvages showed some grade of myelodepression, being severe or extremely severe in 23.3%, with another case of death. Neoadjuvant chemotherapy with CDDP and 5-FU seems promising in advanced cervical carcinoma and is acceptably well tolerated. In contrast, salvage therapy with the same regime yields worse results and is much more toxic. PMID- 8508875 TI - Carcinoma of the cervix in pregnancy. Case report. PMID- 8508876 TI - Immature teratoma of the ovary. AB - The clinicopathologic experience of 10 patients with immature ovarian teratoma is presented. The mean age of the patients was 22.1. Abdominopelvic mass was the presenting symptom in the majority of cases. Immature ovarian teratomas accounted for 4.0% of germ cell tumors and 2.1% of all ovarian neoplasms diagnosed in our institution. Of the patients, 6 had Stage I disease and 7 had grade I tumor. Unilateral tumor was encountered in the majority of patients. Adequate primary surgical-pathologic staging and multiagent chemotherapy seem to be the treatment of choice. PMID- 8508877 TI - The role of follow-up after treatment for gynecologic cancer. AB - The quality of life of the genital cancer patient may be considered in its many different aspects and principally from a medical, sexual and psychological point of view. In order to verify whether a substantial modification of the variable "anxiety" and of the bipolar axis male-female exists, we are conducting a research on our patients undergoing oncologic follow-up (806 patients, treated from 1975 to 1990). The result shows that the state "anxiety" decreases after follow-up examination; on the contrary to trait "anxiety" increases before and after follow-up examination. More complete information could perhaps be obtained having knowledge of the patient's personality, attitudes, feelings etc. PMID- 8508878 TI - Pseudomyxoma peritonei: treatment with intraperitoneal 5-fluorouracil. AB - Four patients with pseudomyxoma peritonei associated with mucinous tumors of the ovary were treated with cytoreductive surgery followed by intraperitoneal (IP) 5 fluorouracil (5-FU). CA-125 was elevated in three, and ca cinoembryonic antigen (CEA) in one patient; both fell to within normal levels following treatment. Two patients underwent reassessment laparotomy and one a reassessment laparoscopy with no evidence of disease following chemotherapy. The fourth patient refused surgical reassessment but remains clinically free of disease. Intraperitoneal 5 FU appears to be effective in pseudomyxoma peritonei. Precis: Four patients with pseudomyxoma peritonei associated with ovarian tumors were successfully treated with surgery and intraperitoneal 5-FU. PMID- 8508879 TI - Therapy of vulvar carcinoma. AB - 83 vulvar carcinoma patients were originally treated in the period between 1970 and 1990. 82 patients presented with squamous cell carcinoma. 70% of the patients were in Stage I or II. It was originally possible to operate on 74 of the 83 patients. A simple or partial vulvectomy was applied 17 times. A bilateral inguinal lymph node excision additionally took place in 6 cases. 51 patients were subjected to radical vulvectomy with inguinofemoral lymph node excision. In 13 cases, pelvic lymph node extirpation was also performed. A posterior pelvic exenteration was performed in 6 cases presenting extensive carcinoma involvement of the vulva. In the remaining 9 patients, either it was not possible to operate, or a nonradical operation could be performed. The primary morbidity, consisting of wound healing disturbances and infections, amounted to 50% in our group. We observed lymphedema in 47% of the cases, although it was clinically important in only 10%. We did not have any primary surgical mortality. The 5-year survival rate was 82% in our patients without inguinofemoral lymph node involvement and only 40% in lymph node metastatic cases. The absolute 5-year cure rate was 66%, or 69% corrected. To be able to give increased preference to less invasive methods an improved prevention and clarification procedure for physicians and patients is necessary. PMID- 8508880 TI - Results of the combination of cisplatin, adriamycin and cyclophosphamide in the treatment of ovarian carcinoma. AB - Forty-seven women affected by Stage Ic-IV epithelial carcinoma of the ovary were treated with the combination of cisplatin, adriamycin (40-50 mg/m2 day 1), and cyclophosphamide (800 mg/m2 day 1) (CAP). Two different schedules of cisplatin were used: 20 mg/m2 day 1-->5 (CAP 5), or 80 mg/m2 on day 1 (CAP 1). In the group of patients with measurable disease the overall response rate was 52%, with a 19% complete response rate. The mean disease-free survival of patients without measurable disease was 24.0+ months. The mean survival of the whole group was 29.2+ months. The mean survival of patients with measurable disease and those without measurable disease was 21.7+ and 35.0+ months respectively. The schedule of cisplatin employed did not influence disease-free survival since the difference between the CAP 1 (21+ months) and the CAP 5 (25+ months) groups was not statistically significant. However the CAP 5 schedule seemed to be better tolerated since it of allowed the delivery be 99% of the planned dose of CDDP, while in the CAP 1 group the dose of CDDP given was only 74% of that planned. PMID- 8508881 TI - Endocervical detection of CIN. Cytobrush versus cotton. AB - Correct methods of sampling are essential for obtaining adequate smears for cytological diagnosis of cervicovaginal abnormalities. In this paper we report on 3 methods of sampling, Ayre spatula, cotton swab and cytobrush on 89 patients who underwent repeat smear and colposcopic examinations because of abnormal screening smears. The cytobrush device was better than Ayre spatula or cotton in collecting both endocervical and neoplastic cells. However, the combination of spatula and cotton was almost the same as spatula and cytobrush in recovering neoplastic cells. Therefore the rate of cervical intraepithelial neoplasia (CIN) diagnosis is more influenced by an adequate sampling of the endocervix than by the type of endocervical device. PMID- 8508883 TI - Cervical intraepithelial neoplasia in HIV seropositive patients. AB - In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations. PMID- 8508882 TI - Primary malignant melanoma arising in an ovarian dermoid cyst: proposed use of radioimmunoscintigraphy with 99mTc-F(ab')2 antimelanoma antibody for staging and follow-up. Case report. AB - A case of primary amelanotic ovarian malignant melanoma arising in a dermoid cyst is presented. Grossly, inside the cyst, pigmented solid lesions were not detected. Histologically, an area with undeniable malignant microscopic features was revealed and its melanomatous identity was confirmed by positive S-100 protein and melanoma antigen immunoreactivity. Recently, after 21 months from surgery this patient has also undergone radioimmunoscintigraphy (RIS) with 99mTc labelled antimelanomatous antibodies which revealed a possible secondary paracolic localization. Regardless of this evidence, although the patient has always refused chemotherapy and second look surgery for removal of the suspicious area, she is alive 1 year after surgery and now doing well. The authors also report the usefulness of employing the RIS technique in evaluating the metastatic spread in this type of malignancy. PMID- 8508884 TI - Survival in ovarian cancers treated at National Cancer Institute in Naples Italy 1985-1990. AB - Ovarian cancer was reported to be increasing in all developed countries, with the exception of Japan. This increase may partly be due to modified reproductive habits which caused a rise in the age of the first pregnancy, a decrease in the number of pregnancies and a shortening of lactation period. To these factors must be added an extension of ovarian activity caused by early menarche and late menopause. For the reasons stated above and in view of the high mortality of this tumor, a survival study was performed with patients who had undergone operations for ovarian cancer from 1985 to 1990 at the National Cancer Institute in Naples (356 beds, 6500 admissions yearly) where the Hospital Cancer Registry (RTO) is an active service. A total of 159 patients was studied; three of them were lost during the follow-up. The results show a good survival rate both global (28%) and in each stage; a few differences with respect to histological type were also detected. PMID- 8508885 TI - The state of prostate cancer screening in the United States. PMID- 8508886 TI - Surgical treatment of venous leakage: medium-term follow-up. AB - Thirty-eight men aged 26-69 years (mean 58) who failed to achieve a full, sustained erection with intracavernosal injections of papaverine and phentolamine (PIPE) and who had evidence of a venous leak on digital subtraction dynamic cavernosography underwent penile vein ligation. Postoperative follow-up ranged from 7 to 44 months (mean 28). Nineteen patients regained spontaneous erections which would allow intercourse (mean follow-up on these men was 23 months). Of these 19 patients, 5 experienced recurrent loss of potency over a 6- to 17-month period (mean 9 months), 4 of these subsequently responding to intracavernosal therapy. Of the 19 without full erections after ligation, 8 obtained erections which would allow intercourse with intracavernosal injections. Two of these patients subsequently lost their response to injections at 2 and 6 months postoperatively. Eleven men had no benefit from surgery (either with or without injections). Of the total of 27 men with erections allowing intercourse, only 19 made an attempted coitus during the follow-up period. Of 9 men with treatment failure who had undergone repeat cavernosography, 8 had evidence of a persistent leak, usually arising from the cavernosal veins. At the time of this study, 4 men had been re-explored, following which 3 obtained erections with the aid of PIPE. Patients who fail to improve following ligation may benefit from re-investigation and repeat ligation using a different surgical approach. PMID- 8508887 TI - Velocity and flow volume gradients along the cavernosal artery: a duplex and color Doppler sonography study. AB - Duplex and color Doppler sonography were used to assess 130 impotent patients and 8 potent controls. Cavernosal artery diameter, peak flow velocity and volume flow rate were evaluated at the level of the crura of the corpora cavernosa and 1 cm proximal to the corona penis. Potent controls and nonarteriogenic impotent patients showed a 20% reduction in hemodynamic parameters at the periphery of the cavernosal arterial tree. In patients with occlusive disease, involving either the upper arterial tree or the entire course of the cavernosal artery, the gradient was maintained. In patients with selective occlusive disease of the distal segment of the cavernosal artery the hemodynamic gradient almost doubled. Hemodynamic gradients can be identified along the cavernosal artery and provide additional information to arteriographic data for the selection of candidates for penile vascular reconstructive surgery. PMID- 8508888 TI - Ultrasound follow-up of ethanolamine oleate sclerotherapy for spermatoceles. AB - Although sclerotherapy as a treatment for hydroceles has gained in popularity during the last few years, there is no consensus on whether it can also be adopted for the treatment of spermatoceles. We examine here the efficacy and safety of ethanolamine oleate sclerotherapy in cases of spermatocele using ultrasound (US) before treatment and during follow-up. Thirty-seven consecutive outpatients aged 36-84 years (mean 61) with symptoms of 40 spermatoceles (1-3 chambers) treated by sclerotherapy were included in the series. It is concluded that US allows multilocular spermatoceles to be differentiated from hydroceles. Post-treatment US findings are typical, including heteroechoic masses with cystic areas extratesticularly, hyperechoic lines peritesticularly (thickened tunicas) and a thickened scrotal wall. All lesions are reversible, however. US is helpful when assessing the need for resclerotherapy. Ethanolamine oleate proved to be effective as a sclerosant, as 83% of the cases were cured or became significantly better. Complications were few and there were no changes in the epididymis. Ethanolamine oleate sclerotherapy can be recommended as an alternative treatment to surgery, especially in older patients with spermatoceles consisting of 1-3 chambers. PMID- 8508889 TI - Influence of fibrin clot inhibitors on the efficacy of intravesical Bacillus Calmette-Guerin in the treatment of superficial bladder cancer. The Dutch Southeast Cooperative Urological Group. AB - After transurethral resection (TUR) of superficial bladder tumors, intravesical instillations with BCG are successfully used to lower the recurrence rate. The mechanism of the antitumor activity of BCG is not completely understood. After TUR, a fibrin clot is formed on the damaged urothelium. Fibronectin (FN) is part of the clot. It has been demonstrated that binding of BCG to the bladder wall is mediated by FN, and therefore FN seems necessary for the antitumor activity of BCG. This binding can be inhibited by fibrin clot inhibitors, like aspirin and coumarin. A reduced efficacy of BCG in patients with superficial bladder cancer using these drugs has been described. We studied 183 patients with superficial bladder cancer, treated with one or two 6-week courses of intravesical BCG instillations. Of the 42 patients that used fibrin clot inhibitors, 13 (31%) experienced a recurrent tumor, as compared to 56 (40%) of 141 patients who did not use these drugs (p = 0.28). The mean time to recurrence was the same in both groups. These results did not depend on the BCG strain used (Tice or RIVM, p = 0.92) and were not influenced by the use of antibiotics against urinary tract infections. We conclude that in our study fibrin clot inhibitors have no adverse effect on the efficacy of BCG therapy for superficial bladder cancer. PMID- 8508890 TI - Retroperitoneal fibrosis and chronic periaortitis: a new hypothesis. AB - The etiology of retroperitoneal fibrosis (Ormond's disease) has still not been clarified. A new hypothesis postulates chronic fibrosing periaortitis. Atherosclerosis of the abdominal aorta and plaque rupture lead to the liberation of oxidized lipoproteins through the adventitia into the periaortic fatty tissue. This results in a chronic inflammatory process. In support of the periaortitis hypothesis is our finding that 9 of 14 consecutively studied patients with retroperitoneal fibrosis had either proven atherosclerosis of the abdominal aorta or a high probability of this in view of multiple vascular risk factors. No patients had received previous methysergide medication. PMID- 8508892 TI - Retraction notice. PMID- 8508891 TI - Treatment of primary vesicoureteric reflux by polytetrafluoroethylene injection: a middle-term follow-up study. AB - We have selected 38 patients (55 ureters) with primary vesicoureteric reflux successfully treated by endoscopic subureteric injection of Teflon. The success rate after 1 injection was 83.6%. Nine ureters required a 2nd or even a 3rd injection of Teflon to achieve success. The follow-up time for these successfully treated patients was 2-5 years, and results remained stable in 94.5% of cases. Endoscopic injection of Teflon seems to be a reliable alternative to open surgery in the treatment of primary vesicoureteric reflux. PMID- 8508893 TI - Effects of submucosal Teflon paste injection in vesicoureteric reflux: results with 1- and 2-year follow-up data. AB - One hundred refluxing ureters with grades II (n = 65), III (n = 27) and IV (n = 8) vesicoureteric reflux (VUR) were treated with endoscopic submucosal polytetrafluoroethylene (Teflon) paste injection. Reflux stopped in 77 ureters after a single injection and in 13 ureters following a second injection. Two ureters remained with minimal (grade I) residual reflux, whilst in another 5 improvement from grades III and IV to grade II reflux was noted. In 3 ureters reflux remained unchanged, because of lateral ectopia of the refluxing ureteric ostium, hindering the injection of Teflon into the correct position. Re evaluation at 1 year postinjection, of 48 previously cured ureters showed recurrence of reflux in 1 (2%), but no further recurrences were noted in 19 ureters reevaluated after 2 years. PMID- 8508894 TI - Hematuria and voiding disorders in children caused by congenital urethral polyps. Principles of diagnosis and management. AB - Congenital urethral polyps may cause hematuria, various degrees of outflow obstruction and display a variety of, mostly nonspecific micturition abnormalities in young boys and infants, and should be considered and investigated when recurrent or persistent hematuria and voiding disturbances are encountered. Voiding cystography is the best available diagnostic method to detect urethral polyps. Following diagnosis, prompt complete resection of polyp is indicated. Resolution of signs and symptoms and excellent prognosis are the rule in most of the reported cases. In view of the rarity of this significant pathological condition, we present our experience with 6 children who suffered from urethral polyps and outline the principles of diagnostic evaluation and management of the child with urethral polyp. PMID- 8508895 TI - Endoscopic treatment of reflux: experimental study and review of Teflon and collagen. AB - Endoscopic correction of vesicoureteric reflux in children has been performed in several hundred cases with the use of Teflon or cross-linked bovine collagen. The main criticism to this simple procedure is the potential migration of Teflon particles and the local pathological reaction. An experimental study was performed in 20 rabbits injected with Teflon or collagen in the bladder submucosa. A pathological examination of the bladder, lymph nodes, liver, lungs and brain was performed several months after the experiment to study the migration and the local reaction. There is no local granulomatous reaction with collagen while a local granulomatous reaction is found in the site of injection of Teflon and in 1 locoregional lymph node. The colonization of collagen by histiocytes increases with time. No distant granulomatous reaction was noted with both injections on histological examination. A mineralogic technique was applied after homogenisation of the lungs and brain to further investigate the distant migration problem. Rare particles of Teflon were observed in the lungs but not in the brain. The pathological significance of these particles remains unclear, but calls for research for different injection materials. PMID- 8508896 TI - Endoscopic treatment of reflux: migration of Teflon to the lungs and brain. AB - We set out to determine experimentally whether particles of polytetrafluoroethylene migrate to the lungs and brain when relatively small volumes of Teflon paste are injected into the bladder in the manner used to correct reflux. Numerous particles of polytetrafluoroethylene were recovered from these organs within 2 weeks of injection. Those in the brain measured up to 15 microns in diameter, indicating that the pulmonary bed is an inefficient filter of particles gaining access to the venous circulation. Although clinically no adverse neurological effects have hitherto been reported, this study suggests that following the 'sting' procedure, some particles may lodge in the brain where they can block the cerebral microcirculation. We believe these findings represent a contraindication to the use of Teflon paste in children. PMID- 8508897 TI - Functional bladder replacement after radical cystectomy in the female: experimental investigation of a new concept. AB - We investigated the possibility of forming a continent surrogate bladder for female patients with the (ileo-) cecal pouch and the in situ appendix as a neo urethra. Five female mongrel dogs were used for an acute animal model. Cuff electrodes were placed around the pelvic and pudendal nerve under general anesthesia and urethral pressures in response to stimulation were recorded. Baseline data were obtained, a nerve-sparing cystectomy was carried out, and the pressure response to stimulation was reassessed. The pressures obtained with pelvic nerve stimulation ranged from 20 to 35 cm H2O (average 28 cm H2O) before and from 10 to 30 cm H2O (average 25 cm H2O) after cystectomy. Urethral pressure changes secondary to pudendal nerve stimulation remained nearly unchanged after cystectomy. Four female human cadavers were used to demonstrate a technique of nerve-sparing cystectomy, comparable to that for male patients. Preservation of the nerves supporting the urethra and the pelvic floor can be achieved by careful preparation close to the bladder in the region between the uterine and vaginal arteries and in the distal perivesical area. The autonomic nerve fibers appear to be protected by the perivesical vascular plexus. As it is not necessary to perform an anastomosis in the true pelvis when using this method, the procedure appears comparatively straightforward. The continence mechanisms of the pelvic floor would not be affected by sutures and subsequent scarring. PMID- 8508898 TI - Efficiency of extracorporeal shockwave lithotripsy on calcium-oxalate stones: role of copper, iron, magnesium and zinc concentrations on disintegration of the stones. AB - Clinical use of extracorporeal shockwave lithotripsy (ESWL) in the noninvasive management of urinary calculi is highly effective and practical. But its results vary in relation to several factors including localization, size and the chemical composition of the stones. Moreover, the anatomy of the kidneys treated is another contributing factor to the success rate of ESWL in upper urinary tract stones. Currently, except cystine and struvite stones, the efficiency of ESWL has been proved and has become the most outstanding therapy for calculi in a great number of stone centers. In this study, the efficiency of ESWL treatment in respect to the concentrations of 4 different trace elements (Cu, Fe, Mg and Zn) in the chemical composition of Ca-oxalate monohydrate stones have been evaluated in 20 patients. PMID- 8508899 TI - Technique of percutaneous electrode implantation for electrical pelvic floor stimulation. AB - A modified technique of electrical pelvic floor stimulation is described in detail. Six patients suffering from detrusor urinary incontinence underwent percutaneous electrode implantation for electrical pelvic floor stimulation. By this procedure adequate muscle contraction was obtained with a significant rise in urethral closure pressure. Detrusor reflex thresholds were increased in 5 of 6 patients at the initial stimulation. Percutaneous implantation appears to be an easy and noninvasive technique. This method provides stable and adequate effects on the pelvic floor structure and may be used in chronic electrical stimulation. PMID- 8508900 TI - Acute pancreatitis following transurethral resection of prostate. AB - Three cases of acute pancreatitis following transurethral resection of the prostate are reported. The incidence is rare. A review of perioperative data failed to disclose any unique factor except in 1 patient who had an underlying biliary tract disease. Hyperamylasemia or hyperlipaemia in association with abdominal pain and vomiting was noted in all patients to establish the diagnosis. Computed tomography also confirmed the existence of acute pancreatitis. One patient died of respiratory and renal failure. However, early diagnosis and prompt treatment are essential to reduce high mortality. In conclusion, acute pancreatitis should be considered as one of the differential diagnoses in the presence of abdominal pain with vomiting, azotemia or oliguria after transurethral resection of the prostate. PMID- 8508901 TI - Rare complication of circumcision: penile amputation and reattachment. AB - We report a case of traumatic penile amputation which occurred accidentally during a ritual circumcision in a 10-year-old boy. A successful penile reattachment was accomplished. Additionally, we discussed the causes and prevention of this condition. PMID- 8508902 TI - Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma. AB - Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO 1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma. PMID- 8508903 TI - Ethyl all-cis-5,8,11,14,17-icosapentaenoate modifies the biochemical properties of rat very low-density lipoprotein. AB - The biochemical properties of serum very low-density lipoprotein (VLDL) were investigated in rats given highly purified all-cis-5,8,11,14,17-icosapentaenoate (EPA), an ethyl-ester derivative (EPA-E). The elution time (gel filtration) of VLDL from EPA-E-treated serum was increased significantly compared with that of the control. EPA-E-treated VLDL isolated by ultracentrifugation exhibited a marked decrease in triglyceride content with a relative increase in cholesterol. In treated VLDL, a significant increase in the ratio of apo E/apo C was observed. There was a remarkable increase in the content of EPA in all the fractions of phospholipids, cholesteryl esters and triglycerides after EPA-E treatment, resulting in n-3 polyunsaturated fatty acid-rich VLDL. EPA-E also reduced the incorporation of [14C]oleate into triglycerides in hepatic microsomes and the rate of hepatic triglyceride secretion. Moreover, lipoprotein lipase activity in heparin-injected plasma was increased in rats given EPA-E without there being an effect on hepatic triglyceride lipase activity. These findings indicate that EPA E exerts an inhibitory effect on hepatic triglyceride synthesis/secretion and a stimulatory effect on triglyceride degradation, resulting in a reduction in particle size and an increase in the ratio of apo E/apo C. Triglyceride-poor and EPA-rich VLDL may rapidly be converted into the density of intermediate low density lipoprotein and low-density lipoprotein and/or may be absorbed into the liver rapidly. PMID- 8508904 TI - Sigma receptor binding affinity and inhibition of apomorphine-induced climbing. AB - Several relatively selective compounds with affinity for the sigma binding site were assessed for their ability to inhibit apomorphine-induced climbing in the mouse. Although, the majority of compounds inhibited apomorphine-induced climbing, there was no correlation between the ability to inhibit climbing and potency in sigma binding assays using [3H]1,3-di-o-tolylguanidine (DTG) or [3H](+)-pentazocine as ligands. The potency of the compounds to inhibit binding to muscarinic M1 or M2 receptors correlated with the potency to inhibit apomorphine-induced climbing. However, several of the compounds that inhibit climbing had microM affinity at muscarinic receptors. Whether these concentrations were achieved in vivo is unclear. Our data suggest that sigma activity per se is not responsible for inhibition of apomorphine-induced climbing. PMID- 8508905 TI - Studies of the biochemical basis for the discriminative properties of 8-hydroxy-2 (di-n-propylamino)tetralin. AB - The ability of a series of compounds to mimic the stimulus properties of 8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was compared to: (1) the affinity of these compounds for the 5-HT1A receptor; and (2) their efficacy to inhibit forskolin-stimulated adenylate cyclase activity. Although for nine compounds (flesinoxan, MDL 73005EF, gepirone, ipsapirone, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) complete cross generalization was associated with high affinity for the 5-HT1A receptor, eltoprazine, d lysergic acid diethylamide and BMY 7378 had pKD > 7.44, but did not show complete mimicry of 8-OH-DPAT. In addition, indorenate had a pKD of 7.88, yet the behavioral response was indistinguishable from the saline control. Because the above data indicated that affinity for the 5-HT1A receptor was necessary, but not sufficient for a receptor ligand to mimic 8-OH-DPAT, the in vitro efficacy of the various compounds at the 5-HT1A receptor was determined by measuring inhibition of forskolin-stimulated adenylate cyclase activity in hippocampal membranes. For a series of drugs (gepirone, ipsapirone, flesinoxan, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) significant inhibition of forskolin stimulated adenylate cyclase activity was observed, and these same drugs showed complete cross generalization. However, BMY 14802 and MDL 73005EF did not alter adenylate cyclase activity, yet completely mimicked the stimulus properties of 8 OH-DPAT. Eltoprazine had significant efficacy in inhibiting forskolin-stimulated adenylate cyclase activity, but only 30% of the responses following administration of this drug were on the 8-OH-DPAT-appropriate lever. Furthermore, although indorenate inhibited hippocampal adenylate cyclase activity, the behavioral response to this compound was indistinguishable from the saline control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508906 TI - Protein kinase C inhibitors suppress disc-sphere changes of human platelets, as assessed with the shape-change parameter. AB - Changes in the shape of human platelets and the biochemical mechanism responsible were evaluated, using the shape-change parameter. Neither the Na+/H+ exchanger, nor intracellular or extracellular calcium ions (Ca2+) affected disc-sphere changes induced by low doses of thrombin. Treatment with inhibitors of Ca2+ mobilization, calmodulin or mysoin light-chain kinase had no significant effect on the shape change of platelets. Staurosporine and H-7, both of which are inhibitors of protein kinase C, inhibited disc-sphere changes at low concentrations. Moreover, calphostin C, a specific inhibitor of protein kinase C, effectively inhibited thrombin-induced shape change, as assessed by the shape change parameter, in a dose-dependent manner. 1-Oleoyl-2-acetyl-glycerol and 1,2 dioctanoyl-glycerol, which are synthetic protein kinase C activators, induced shape changes similar to those induced by thrombin. A decrease in the surface area of platelet images on scanning electron micrographs was used to quantify the disc-sphere transformation. The mean platelet areas was significantly decreased after stimulation with thrombin or 1-oleoyl-2-acetyl-glycerol. Pretreatment with H-7 inhibited the thrombin-induced disc-sphere change, as assessed by changes in the platelet surface area. Our results obtained with various inhibitors suggest that thrombin-induced platelet change, as assessed by the shape-change parameter, are associated with activation of protein kinase C. PMID- 8508908 TI - Haloperidol interacts with the strychnine-insensitive glycine site at the NMDA receptor in cultured mouse hippocampal neurones. AB - N-Methyl-D-aspartate (NMDA)-evoked responses in voltage-clamped hippocampal neurones in culture were reversibly, but not completely, attenuated on superfusion with micromolar concentrations (0.1-100 microM) of haloperidol with an IC50 (+/- S.E.M.) value of 1.9 +/- 0.2 microM (n = 7). In contrast, kainate- and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-evoked responses were relatively unaffected on application of 50 microM haloperidol. The NMDA receptor antagonist action of haloperidol was neither competitive in nature nor voltage-dependent but was reduced upon elevation of the extracellular concentration of glycine. Furthermore, in the absence of added glycine haloperidol (at 0.1 microM) frequently potentiated NMDA-evoked responses. Haloperidol thus appears to be a partial agonist for the strychnine-insensitive glycine site associated with the NMDA receptor-channel complex. PMID- 8508907 TI - Dihydroergosine: anticonflict effect in rats and enhancing effects on [3H]muscimol binding in the human brain post mortem. AB - The anticonflict activity of the ergot alkaloid, dihydroergosine, a drug which binds to 5-hydroxytryptamine1 (5-HT1) receptors and to gamma-aminobutyric acidA (GABAA) receptor-associated Cl- ionophore, was studied in water-deprived rats. In vitro effects of this drug on [3H]muscimol and [3H]flunitrazepam binding to the crude synaptosomal pellet of the human frontal cortex post-mortem were also investigated. Dihydroergosine, given 2 h prior to testing, enhanced drinking under punished (0.8 mA) conditions, and diminished it under unpunished conditions. The mechanism of this effect was (-)-propranolol- and pindolol insensitive and picrotoxin-sensitive. Flumazenil either failed to affect, or at a higher dose (10 mg/kg), counteracted the dihydroergosine-induced enhancement of punished drinking. This dose of flumazenil was itself anxiogenic. Dihydroergosine had mild sedative and analgesic properties. Low concentrations of dihydroergosine (10 nM to 100 microM) enhanced the binding of [3H]muscimol but not of [3H]flunitrazepam. The results suggest that dihydroergosine may possess anxiolytic properties presumably mediated by its specific action at the GABA/benzodiazepine/chloride channel complex. PMID- 8508909 TI - Localization of angiotensin AT1 receptors in the rat heart conduction system. AB - We characterized angiotensin II receptor subtypes in the conduction system of the rat heart using quantitative autoradiography. In both the sinoatrial and atrioventricular nodes, binding could be totally displaced by losartan, and was insensitive to PD 123177, indicating that angiotensin II receptors in the conduction system of the rat heart belong to the AT1 subtype. Angiotensin AT1 receptors could play a direct role in the regulation of the heart chronotropic properties. PMID- 8508910 TI - Haloperidol and loxapine but not clozapine increase synaptic responses in the hippocampus. AB - Effects of two typical neuroleptics haloperidol and loxapine, and an atypical antipsychotic clozapine on excitatory synaptic transmission were examined in the CA1 area of rat hippocampal slices. Haloperidol (10 mumol) and loxapine (10 mumol) increased extracelllar evoked field potentials by an average of 57 and 125% of the control level respectively. Clozapine (50 mumol) induced a transient depression (21% of control) of the response followed by a small augmentation (10%). Examination of haloperidol actions using the whole cell clamp technique showed an increase in the amplitude of the excitatory postsynaptic current (e.p.s.c.) in response to the drug without any apparent changes in the resting membrane current. These data suggest that haloperidol and loxapine may act by enhancing excitatory synaptic transmission in some areas of the brain, and that novel antipsychotic clozapine differs in its mechanism of action. PMID- 8508911 TI - Effects of a nonpeptide angiotensin II receptor antagonist (CV-11974) on [Ca2+]i and cell motion in cultured ventricular myocytes. AB - We studied the effects of angiotensin II and CV-11974 (a newly synthesized angiotensin II receptor antagonist) on cell contraction and [Ca2+]i in cultured neonatal rat ventricular myocytes. Exposure of these cells to 10 nM angiotensin II significantly decreased peak systolic cell position (60.1 +/- 3.3% of the control, P < 0.01) and peak systolic [Ca2+]i (from 1111 +/- 250 to 572 +/- 143 nM, P < 0.05) within 60 s. Pretreatment of ventricular myocytes with CV-11974 (10 100 nM) completely suppressed the angiotensin II-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that CV-11974 inhibits cardiac angiotensin II receptors. PMID- 8508912 TI - Long-lasting reciprocal changes in striatal dopamine and acetylcholine release upon morphine withdrawal. AB - In superfused rat striatal slices, the electrically evoked release of [3H]dopamine was reduced by about 30% and that of [14C]acetylcholine was enhanced by about 25% no less than 3 weeks after morphine withdrawal in rats chronically treated with the opiate for 6 days. The lasting nature of the reduced dopamine release at the level of dopaminergic nerve terminals and the concomittant enhanced excitability of neurons tonically inhibited by released dopamine, such as cholinergic interneurons, could play an important role in the maintenance of opiate dependence. PMID- 8508913 TI - Site-directed mutagenesis in hemoglobin. Effect of some mutations at protein interfaces. AB - The role of selected amino acid residues in the monomer-monomer contacts of Hb A has been studied by site-directed mutagenesis of the alpha chain bearing substitutions in the subunit surfaces. Mutation alpha 38Thr-->Trp induced a stabilization of tetrameric Hb-CO with a decrease of the Kd for the equilibrium alpha 2 beta 2<==>2 alpha beta, but had not effect on ligand binding. Mutation alpha 40Thr-->Arg resulted in a complete loss of cooperativity in ligand binding. Mutation alpha 103His-->Val had no noticeable effect. We also studied the behaviour of isolated, mutated alpha chains with respect to self association: compared to wt alpha chains, mutant alpha 38Thr-->Trp showed stabilization of the dimeric state and (at high protein concentration) a detectable amount of tetramers. Mutant alpha 103His-->Val showed only a minor stabilization of the alpha 2 dimer. PMID- 8508914 TI - A distal region of the CALC-1 gene is necessary for regulated alternative splicing. AB - The CALC-1 gene exhibits tissue specific alternative splicing with exons 1-4 being spliced to produce the calcitonin mRNA in thyroid C cells and exons 1-3 and 5-6 being joined to produce the CGRP mRNA in neuronal cells. Previous studies have identified an element in intron 3 within the alternatively spliced region which is critical for this effect to occur. We show here that deletion of sequences downstream of the alternatively spliced region also disrupts the tissue specific pattern of alternative splicing. The manner in which these sequences act is discussed. PMID- 8508915 TI - Novel antimicrobial peptides from skin secretion of the European frog Rana esculenta. AB - Three antimicrobial peptides were isolated from skin secretion of the European frog, Rana esculenta. Two of them show similarity to brevinin-1 and brevinin-2, respectively, two antimicrobial peptides recently isolated from a Japanese frog [Morikawa, N., Hagiwara, K. and Nakajima, T. (1992) Biochem. Biophys. Res. Commun. 189, 184-190]. The third one, named esculentin, is 46 residues long and represents a different type of peptide. All these peptides have as a common motif an intramolecular disulfide bridge located at the COOH-terminal end. The peptides from R. esculenta show distinctive antibacterial activity against representative Gram-negative and Gram-positive bacterial species. In particular, esculentin is the most active against Staphylococcus aureus, and has a much lower hemolytic activity. PMID- 8508916 TI - Crystallization of the seryl-tRNA synthetase:tRNAS(ser) complex of Escherichia coli. AB - Crystals of the complex between seryl-tRNA synthetase and tRNA(2ser) from Escherichia coli have been obtained from ammonium sulphate solutions. The crystals are of the 1:2 enzyme:tRNA complex, belong to the space group C222(1), have cell dimensions of a = 128.9 A, b = 164.9 A, c = 127.3 A and diffract anisotropically from 3.5 to 4.5 A. An X-ray diffraction data set to 4 A has been collected. The combination of molecular replacement using the refined structure of the catalytic domain of the native enzyme, data from a heavy atom derivative and solvent flattening was used to produce a map at 4 A resolution. This shows that a tRNA molecule binds across the dimer, the anticodon stem and loop do not contact the protein and the helical arm of the enzyme contacts the T psi C loop and the long extra arm of the tRNA. PMID- 8508917 TI - Glutamate receptors of Drosophila melanogaster. Primary structure of a putative NMDA receptor protein expressed in the head of the adult fly. AB - The NMDA subtype of ionotropic glutamate receptors has been implicated in the activity-dependent modification of synaptic efficacy in the mammalian brain. Here we describe a cDNA isolated from Drosophila melanogaster which encodes a putative invertebrate NMDA receptor protein (DNMDAR-I). The deduced amino acid sequence of DNMDAR-I displays 46% amino acid identity to the rat NMDAR1 polypeptide and shows significant homology (16-23%) to other vertebrate and invertebrate glutamate receptor proteins. The DNMDAR-I gene maps to position 83AB of chromosome 3R and is highly expressed in the head of adult flies. Our data indicate that the NMDA subtype of glutamate receptors evolved early during phylogeny and suggest the existence of activity-dependent synaptic plasticity in the insect brain. PMID- 8508918 TI - Rabbit masseter expresses the cardiac alpha myosin heavy chain gene. Evidence from mRNA sequence analysis. AB - The presence of myosin alpha heavy chain in the rabbit masseter has been previously suggested at the protein level [(1991) Basic App. Myol. 1, 23-34; (1991) Histochem. J. 23, 160-170]. To confirm this finding, we cloned most of the mRNA corresponding to the myosin heavy chain S2 subfragment. PCR analysis and subsequent nucleotide sequence determination of the amplified cDNA demonstrates the presence of a myosin alpha heavy chain mRNA in rabbit masticatory muscles. PMID- 8508919 TI - A tandem repeat of the SPKK peptide motif induces psi-type DNA structures at alternating AT sequences. AB - The interaction between a tandem repeat of the SPKK peptide motif and calf thymus DNA or several polynucleotides has been investigated by circular dichroism. The octapeptide SPKKSPKK does not induce any important changes in the CD spectra of the polynucleotides poly(dG).poly(dC), poly(dG-dC).poly(dG-dC) and poly(dA).poly(dT) while the spectrum of calf thymus DNA is slightly modified. Binding of this basic peptide to the alternating copolymer poly(dA-dT).poly(dA dT) results in a marked psi-type condensation in a manner similar to that induced by the entire C-terminal domain of histone H1. PMID- 8508920 TI - Correlation between phospholipase A2 activity and intra-Golgi protein transport reconstituted in a cell-free system. AB - A wide variety of phospholipase A2 inhibitors blocks intra-Golgi protein transport reconstituted in a cell-free system. Phospholipase A2 activity detectable under the protein transport assay conditions is actually inhibited by the inhibitors. There is a good correlation between the inhibition of protein transport and that of phospholipase A2 activity. Prolactin secretion from GH3 cells is also blocked by a membrane-permeable phospholipase A2 inhibitor, suggesting the physiological relevance to inhibition of protein transport in vitro by phospholipase A2 inhibitors. PMID- 8508921 TI - Expression of Kv2.1 delayed rectifier K+ channel isoforms in the developing rat brain. AB - Mammalian central neurons regulate a diverse set of functions by changes in spatial and temporal expression patterns of a large family of K+ channel gene products. Here the temporal patterns of expression of Kv2.1 (drk1) K+ channel mRNAs and polypeptides have been studied in rat brain. Northern blots using Kv2.1 specific probes show that three size classes (4.4, 9.0, 11.5 kb) of Kv2.1 K+ channel transcripts are present in rat brain. These mRNAs show differential patterns of expression over embryonic and postnatal developmental, with the 4.4 kb transcript being the predominant embryonic Kv2.1 mRNA, and the 11.5 kb transcript being the predominant adult mRNA. Immunoblots using Kv2.1-specific site-directed antibodies show the existence of multiple Kv2.1 polypeptides, which differ in their mobility on SDS polyacrylamide gels, in their immunoreactivity to a carboxyl terminal-directed anti-Kv2.1 antibody, and in their developmental expression. Thus Kv2.1 polypeptide isoforms exhibit discrete temporal patterning during neuronal development, implying distinct roles for these channel proteins in vivo. PMID- 8508922 TI - Ras proteins increase Ca(2+)-responsiveness of smooth muscle contraction. AB - G-proteins may be involved in receptor-mediated Ca(2+)-sensitization of smooth muscle contraction, but the responsible G-proteins are not yet known. Here we show that in beta-escin skinned mesenteric microarteries, H-ras p21 proteins, preactivated with GTP or GTP gamma S, increase force at constant submaximal Ca2+ (pCa 6.3) concentration dependently. The GTP-bound form of the wild-type H-ras p21 and the oncogenic mutant (p21[G12V]) were equally effective. The nucleotide free and the inactive GDP-bound form of ras p21 had no effect on force. The tryosine kinase inhibitor, tryphostin, partially reversed the effect of the ras proteins in the GTP-bound form on force. Thus, ras proteins mimic the Ca(2+) sensitizing effect of GTP gamma S and vasoconstrictors in mesenteric microarteries which may involve tyrosine phosphorylation. PMID- 8508923 TI - In vitro reconstitution of the proteolytic system responsible for hydrolysis of the 13S globulin in buckwheat seeds. AB - The reconstruction of the proteolytic system responsible for the profound hydrolysis of the main storage protein of buckwheat seeds, 13S globulin, has been carried out in vitro. It was found that subsequent action of a metalloproteinase from dry buckwheat seeds and cysteine proteinase and carboxypeptidase from growing seedlings led to a profound hydrolysis of the storage protein. The 13S globulin that was not hydrolyzed with metalloproteinase was not degraded by the proteolytic enzymes of growing seedlings. A scheme is proposed, which describes the functioning of the proteolytic system hydrolyzing the storage protein in growing buckwheat seedlings in vivo. PMID- 8508924 TI - Cloning and functional expression of a brain G-protein-coupled ATP receptor. AB - A cDNA encoding a novel member of the G-protein-coupled receptor (GCR) superfamily, an ATP receptor, has been isolated from an embryonic chick whole brain cDNA library by hybridization screening. The encoded protein has a sequence of 362 amino acids (41 kDa) and shares no more than 27% amino acid identity with any known GCR. When expressed as a complementary RNA (cRNA) in Xenopus oocytes a slowly-developing inward current was observed in response to application of ATP. The pharmacology of this expressed protein defines it as a P2Y purinoceptor. PMID- 8508925 TI - Identification, sequence analysis, and characterization of cDNA clones encoding two granzyme-like serine proteinases from rat duodenum. AB - Clones of cDNA encoding two serine proteinases were isolated from a cDNA library prepared from rat duodenum mRNA. The deduced amino acid sequences consisted of 248 residues and possessed a high level of homology to one another and to the sequences of granzymes, cathepsin G, and mast cell proteases I and II. Analysis of the enzymes' primary structures allowed the identification of the catalytic amino acid triad and the prediction of the substrate specificity. Northern blotting experiments showed that while one of these proteinases is expressed only in duodenum, the other enzyme is present in duodenum, lung, and spleen. It is supposed that these proteinases may play an important role in the function of an organism's defence systems. PMID- 8508926 TI - Amyloidogenicity of rodent and human beta A4 sequences. AB - Previously we have shown that aggregation of the C-terminal 100 residues (A4CT) of the beta A4 amyloid protein precursor (APP) and also of beta A4 itself depends on the presence of metal-catalyzed oxidation systems [T. Dyrks et al. (1988) EMBO J. 7, 949-957]. We showed that aggregation of the amyloidogenic peptides induced by radical generation systems requires amino acid oxidation and protein cross linking. Here we report that aggregation of A4CT and beta A4 induced by radical generation systems involves oxidation of histidine, tyrosine and methionine residues. The rodent beta A4 sequence lacking the single tyrosine and one of the three histidine residues of human beta A4 and a beta A4 variant in which the tyrosine and the three histidine residues were replaced showed a reduced tendency for aggregation. Thus our results may explain why beta A4 amyloid deposits could so far not been detected in the rodent brain. PMID- 8508927 TI - Thermal transitions in the purple membrane from Halobacterium halobium. AB - The application of a successive annealing procedure to the scanning calorimetric endotherm of the purple membrane from Halobacterium halobium in phosphate buffer, pH 7.5, leads to five thermal transitions beneath the overall endotherm. Circular dichroism and fluorescence experiments have also been carried out with the native membrane heated at the same scan rate as in calorimetric runs (1 degrees C/min) as well as with previously heated membrane samples. These results, together with others from the literature, have been used to suggest a preliminary explanation of the five thermal transitions. PMID- 8508929 TI - Collaboration between nursing education and nursing research. PMID- 8508928 TI - The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non selectively. AB - CHO cells express both of the phosphoinositidase C-linked G-proteins Gq and G11. G11 alpha is some 2.5-fold more highly expressed than Gq alpha in membranes of these cells. Following transfection and stable expression of CHO cells with DNA encoding the human muscarinic M1 acetylcholine (HM1) receptor, chronic treatment of the cells with the cholinergic agonist carbachol resulted in down-regulation of membrane levels of both Gq alpha and G11 alpha. Dose-response curves to carbachol produced identical EC50 values for agonist-induced down-regulation of the two G-proteins and both were down-regulated with the same time course. These data indicate that the HM1 receptor interacts with the activates both Gq alpha and G11 alpha equivalently and non-selectively in a whole cell system in which the receptor has access to both G-proteins. PMID- 8508930 TI - Think twice about relying on employer liability coverage. PMID- 8508931 TI - HIV: what employers need to know. PMID- 8508932 TI - If Florence Nightingale (1820-1910) came back today. PMID- 8508933 TI - Establishment of a system for volunteer nurses. PMID- 8508934 TI - Nursing after retirement. PMID- 8508935 TI - Absorbed doses from computed tomography for dental implant surgery: comparison with conventional tomography. AB - Tomography is often needed prior to implant surgery to evaluate jaw bone dimensions. Computed tomography (CT) is advocated as an alternative. The purpose of this study was to measure the absorbed doses to radiosensitive organ in the head and neck region when CT is used. Measurements were made with extruded LiF thermoluminescent dosemeters within and on an anthropomorphic phantom examined with a Philips Tomoscan LX CT scanner. Axial scanning was performed for the maxilla and both frontal, perpendicular to the alveolus, and axial for the mandible. The highest absorbed doses were at the skin surface, 38 mGy with maxillary scans, and from axial and frontal scans of the mandible 35 mGy and 37 Gy, respectively. The parotid dose was 31 mGy from maxillary scans and in the mandible the submandibular gland dose was 27 mGy with axial scanning and 16 mGy with frontal. The eye lens received its highest dose (5.5 mGy) from frontal scans of the mandible. Although outside the scanning plane the pituitary and the thyroid glands received comparatively high absorbed doses of 0.6-4.0 mGy. All organ doses measured were considerably higher than those reported for conventional tomography. PMID- 8508936 TI - Dose reduction to the thyroid gland in intraoral source radiography. AB - Organs near the oral cavity may be exposed to unacceptably high levels of radiation in intraoral source radiography. Three methods for reducing the dose to the thyroid gland have been investigated. A restriction of the exposure geometry by use of the B and C types of applicator was an efficient means of dose reduction. Absorbed doses to the thyroid gland were 30-50% less than those obtained when using the A-type applicator. A 10 degree upward inclination of the occlusal plane reduced the dose by 20%. In contrast, three thyroid protectors had no effect on dose reduction. PMID- 8508937 TI - Assessment of a new processor containing a self-cleaning synthetic-web transport mechanism. AB - The effect of two different types of automatic X-ray processing machines (a roller-based Pantomat P10 and the Velopex which has a novel web transport system) on the accuracy of radiographic diagnosis of caries in extracted premolars was evaluated. Seven observers graded the occurrence of caries and their findings were compared with actual prevalence of the disease. The accuracy was measured with the ROC technique. Kodak Ektaspeed dental X-ray film was used. The results showed no significant differences in diagnostic accuracy between the two developing machines. The Velopex gave a check pattern to the films, but it was not so marked as to have a major influence on diagnostic accuracy. PMID- 8508939 TI - Dentomaxillofacial radiology, a journal of head and neck imaging. PMID- 8508938 TI - Comparison of panoramic and intraoral radiography for the diagnosis of caries and periapical pathology. AB - Panoramic and intraoral radiographs from 400 consecutive patients were compared for their ability to demonstrate periapical pathology and caries. Two hundred panoramic radiographs were exposed with the rotational technique and 200 with the intraoral X-ray tube technique. Periapical osteolytic and sclerotic lesions as well as approximal caries were recorded independently by two observes. Agreement with intraoral radiographs for periapical osteolytic lesions was, on average, 63% for the rotational and 55% for the intraoral X-ray tube technique and for sclerotic lesions 40% and 36%, respectively. The agreement varied with tooth type and lesion size. When teeth without periapical lesions were also included in the comparisons, the values for agreement were over 96%. Interobserver agreement for periapical osteolytic lesions was 61% for the rotational and 56% for the intraoral X-ray tube technique. The corresponding values for sclerotic lesions were 29% and 23%. Intraobserver agreement for periapical osteolytic lesions was 71% for the rotational and 67% for the intraoral X-ray tube technique. The corresponding values for sclerotic lesions were 46% and 56%. Agreement with intraoral radiographs for enamel caries was, on average, 21% for the rotational and 27% for the intraoral X-ray tube technique and for dentinal lesions 44% and 53%, respectively. When caries-free approximal surfaces were also included in the comparisons, the values for agreement were over 95%. It is concluded that panoramic and intraoral radiography perform equally well as diagnostic tools for the detection of periapical lesions, although the results are not identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508940 TI - Alignment errors in bitewing radiographs using uncoupled positioning devices. AB - Errors in X-ray beam alignment account for many of the exposure errors in bitewing radiography. A new method for measuring these alignment errors is described. The alignment accuracy of two different models of inexpensive plastic positioning devices, used for bitewing radiography, were quantified and compared. The technique involves documenting the alignment of an 'ideal' reference radiograph and successive exposures. It permits calculation of X-ray beam-film alignment errors in all subsequent radiographs using the 'ideal' reference. Bitewing radiographs were taken on 61 patients and 19 of these were re radiographed at 6-month intervals over a 2-year period, providing a total of 156 radiographs for the study. Horizontal and vertical angular deviations were measured and total alignment errors calculated for each radiograph. The average angular alignment error was less than 2 degrees total angular error (1.3-2.4 degrees, 95% confidence intervals). It is concluded that these devices can be used when X-ray beam-film alignment error below 2.5 degrees is acceptable. PMID- 8508941 TI - A tomographic technique for the depiction of atrophied alveolar ridges prior to endosseous implant placement. AB - Radiographic examination is of particular importance prior to the placement of dental implants, especially when the alveolar ridge is severely atrophied. Accurate assessment of the amount of residual bone can be improved with tomography. A method is described which utilizes templates and marking aids to facilitate the correct positioning of the jaws so as to obtain a true cross section of the alveolar ridge at the intended implant sites. The same template can be used to determine the location and angulation of the implant at surgery. PMID- 8508942 TI - An adverse reaction following sialography. AB - Reactions following the administration of iodine are well documented in general radiography, but are unusual following sialography. A patient who experienced an adverse reaction following sialography with an iodine-based, low osmolar, contrast medium, Hexabrix 320, is presented. The reaction consisted of severe shoulder and back pain 24 h after the procedure. A skin rash was identified involving the right axilla, groin and elbow, with swelling visible around the right elbow joint. It was not possible to distinguish, on the basis of the available evidence, between an anaphylactoid and idiosyncratic allergic reaction. PMID- 8508943 TI - The diagnosis of dentinal dysplasia Type 1. PMID- 8508944 TI - A comparison of a new dental X-ray film, Agfa Gevaert Dentus M4, with Kodak Ektaspeed and Ultraspeed dental X-ray films. AB - A new dental X-ray film, Agfa Gevaert Dentus M4, has recently been introduced. Its diagnostic ability for approximal caries and its sensitometric properties were compared with those of Kodak Ultraspeed and Ektaspeed dental X-ray films. Seven general practitioners and six consultants in oral radiology recorded both incipient and manifest approximal caries on radiographs of 100 extracted premolars. ROC-curve technique was used to analyse the results. A significant difference in diagnostic accuracy for both incipient and manifest caries was found between Ektaspeed and Dentus M4, but not between Ektaspeed and Ultraspeed or between Ultraspeed and Dentus M4. Ektaspeed had the highest diagnostic accuracy, 0.79, while Dentus M4 had the lowest, 0.72. No significant differences were found between the different films in their ability to separate sound from cavitated surfaces. The speed and contrast of the three dental X-ray films were measured according to ISO 3665. Dentus M4 film was found to be 1.8 times faster than Ektaspeed and 2.8 times faster than Ultraspeed. Dentus M4 had a lower film contrast than both Ultraspeed and Ektaspeed. Films of the three different types and with about the same expiry date were stored in seven different clinics. One film of each type was developed each month over a 16-month period under standardized conditions. Base plus fog density was measured. The Dentus M4 had a more rapid build up of fog compared to Ultraspeed and Ektaspeed films. We conclude that the new Dentus M4 film has a limited value in the diagnosis of incipient caries. PMID- 8508945 TI - Satellite cells from slow rat muscle express slow myosin under appropriate culture conditions. AB - Satellite cells were isolated at high yields from slow-twitch soleus and fast twitch tibialis anterior (TA) muscles of adult male Wistar rats. The number of satellite cells isolated from soleus muscle exceeded that from TA muscles by a factor of three. A comparison of satellite cells grown on gelatin- or Matrigel coated dishes revealed that Matrigel greatly enhances the maturation of the satellite-cell-derived myotubes. As judged from immunohistochemistry, myosin heavy chain electrophoresis and immunoblot analyses, only cells grown on Matrigel, but not on gelatin, expressed adult myosin isoforms. Slow myosin expression was only detected in Matrigel cultures. Soleus cultures contained, in addition to the majority of myotubes expressing fast myosin, a small fraction (maximally 10%) of myotubes coexpressing fast and slow myosins. The number of fast/slow myosin-containing myotubes was negligible in TA cultures. The expression of slow myosin increased with age. Slow myosin was nonuniformly distributed along the length of specific myotubes and accumulated around some myonuclei. These results point to the existence of myotubes with a heterogeneous population of myonuclei, probably resulting from fusion of differently preprogrammed satellite cells. We suggest that the patch-like expression of slow myosin results from local accumulation of myonuclei of slow-type satellite cells. PMID- 8508946 TI - Differentiation of supernumerary fibres in neonatally deefferented rat muscle spindles. AB - The myofibrillar ATPase (mATPase) activity and the pattern of expression of several myosin heavy chain (MHC) isoforms and of M-protein (M(r) 165,000) were studied in serial cross sections of neonatally deefferented 5- to 8-week-old rat hindlimb muscle spindles with supernumerary intrafusal fibres. In a sample of 5- to 6-week-old neonatally deefferented muscle spindles cut through the A region, the average number of intrafusal fibres per spindle was 8.4 in comparison to 4.2 in control spindles. Parent fibres extended throughout the whole encapsulated portion of the spindle, whereas supernumerary fibres were found only in the A region. The diameters of the supernumerary intrafusal fibres varied from less than 1 micron up to 10 microns approximately. On the basis of the mATPase activity and the pattern of expression of MHC isoforms and of M-protein, the vast majority of the supernumerary fibres could be classified as nuclear bag2, bag1 or chain fibres. However, some supernumerary fibres with small diameters exhibited features that did not fit any of the three known intrafusal fibre types. Two major processes, namely fibre splitting versus activation and fusion of satellite cells, might account for the formation of supernumerary fibres. The data presented suggest the existence of at least two types of intrafusal satellite cells. One type of satellite cell is related to the nuclear bag fibres and gives rise to myotubes which, if they have sensory innervation, can express slow tonic MHC and, therefore, differentiate into a phenotype similar to that seen in nuclear bag fibres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8508947 TI - Different propensity for spontaneous differentiation of cell clones isolated from the human ovarian surface epithelial cell line HOC-7. AB - Limiting dilution culture of cell fractions obtained by discontinuous density gradient centrifugation was used to establish six different cell clones from HOC 7 ovarian adenocarcinoma cells (D1-D3, N1-N3). Clones D1-D3 revealed a phenotype similar to that seen in parental cells exposed to differentiation inducers such as dimethyl sulfoxide (DMSO, 0.8% [v/v]). They were flattened, slowly growing cells (doubling times: 42-46 h). The cells developed long cytoplasmic extensions and adopted a complicated growth pattern. Fixed-cell enzyme-linked immunosorbent assay (ELISA) and Western blotting demonstrated that these cells contained high levels of epidermal growth factor-receptor (EGF-R), carbohydrate antigen 125 (CA 125), fibronectin and desmoplakin, but low levels of myc oncoproteins. However, untreated parental cells and clones N1-N3 were fast-growing (doubling times: 23 28 h), regularly shaped, polygonal cells ("cobblestone" monolayer) with low levels of EGF-R, CA 125, fibronectin and desmoplakin, but relatively higher amounts of myc oncoproteins. The similarity of the sublines to either untreated or inducer-treated parental cells indicated that clones D1-D3 represented spontaneously differentiated HOC-7 cells, whereas clones N1-N3 originated from less-differentiated cells. The features examined in this model cell system proved to be closely related to ovarian cancer cell proliferation and differentiation. The observation of a tumor-inherent propensity for spontaneous differentiation suggests that exogenous stimulation of existing differentiation pathways may represent an alternative approach for tackling the problem of growth control and differentiation in malignant tissues. PMID- 8508948 TI - Human Caco-2 cells transfected with c-Ha-Ras as a model for endocrine differentiation in the large intestine. AB - Endocrine cells occur in approximately 30% of all colorectal adenocarcinomas, and this feature appears to correlate with a relatively poor prognosis. To study the factors regulating endocrine differentiation in colorectal cancer, which may bear resemblance to the regulation of endocrine differentiation in normal intestinal mucosa, models in which differentiation can be manipulated are essential. However, endocrine features in colorectal cancer cell lines are scarce and are almost exclusively observed in xenografts, presumably as a result of differentiation induction by stromal components. We attempted to demonstrate endocrine differentiation in the colonic adenocarcinoma cell line Caco-2, which is frequently used as a model for enterocytic differentiation. In vitro endocrine tumor cells were not encountered. In vivo studies were cumbersome, because of the low take rate of Caco-2 cells. We did manage to establish nude mouse xenografts of Caco-2 cells by inoculating cells in collagen gel and by suppressing natural killer cell activity. In an attempt to induce a better take rate and to investigate the effect of Ras oncoprotein overexpression on endocrine differentiation, Caco-2 cells were transfected with a point-mutated c-Ha-Ras gene. The cell line Caco-2 EJ6, generated from these experiments, could be xenografted in nude mice with a high take rate, yielding a moderately well differentiated adenocarcinoma, morphologically identical to the tumors derived from untransfected Caco-2 cells. The xenografts displayed goblet cell, enterocytic, Paneth cell and endocrine differentiation. In vitro endocrine differentiation was observed neither under standard conditions nor with extracellular matrix components as differentiation inducers. We conclude that the Caco-2 cell line and its c-Ha-Ras transfected subline Caco-2 EJ6 in vivo display endocrine differentiation. Ras overexpression does not enhance endocrine differentiation. Due to its favorable growth properties in vivo, Caco-2 EJ6 is a suitable model for studies on endocrine differentiation in colorectal cancer. PMID- 8508950 TI - Surface display and peptide libraries. Cold Spring Harbor Laboratory, April 4-7, 1992. Proceedings. PMID- 8508949 TI - Molecular analysis of the Wnt-1 proto-oncogene in Ambystoma mexicanum (axolotl) embryos. AB - To analyze Wnt-1 expression during neurulation in urodele embryos, we have isolated a Wnt-1 cDNA clone, Awnt-1, from an Ambystoma mexicanum (axolotl) neurula-stage cDNA library. Awnt-1 codes for a protein of 369 amino acids rich in cysteine residues, is preceded by a hydrophobic leader peptide sequence and contains four possible sites for N-linked glycosylation. The temporal expression profile of Awnt-1 was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Awnt-1 expression in the axolotl embryo is biphasic. Awnt-1 transcripts are found in early blastulae until gastrulation, are barely detectable during gastrulation, and are present again from neurulation until late embryogenesis. Transcripts are present before the midblastula transition, indicating that they might be of maternal origin. To localize Awnt-1 expression in embryos during the first phase of expression, early gastrulae were dissected by cutting along the animal-vegetal and future dorso-ventral axes and analyzed by RT-PCR. At the early gastrula stage Awnt-1 transcripts appear to be located in the future ventral region of the embryo. Hatching larvae no longer express Awnt-1. PCR reactions performed using cDNA library-phage DNA templates derived from whole neurulae versus embryos with the neuroectoderm removed suggest that, in the neurula, Awnt 1 transcripts are located in the neuroectoderm. This suggest that, as is the case for Wnt-1 in other vertebrates, Awnt-1 may be involved in neurogenesis. These results suggest that Wnt-1 has earlier roles in development than has been considered until now. PMID- 8508951 TI - A revised strategy for cloning antibody gene fragments in bacteria. AB - The ability to clone and overexpress genes encoding mouse Fab (antigen-binding fragment) proteins in bacteria led to the development of a methodology which has the potential to replace traditional hybridoma technology [Huse et al., Science 246 (1989) 1275-1281]; however, several observations have suggested that clones with desirable chemical properties may be missed in immunoscreens of large combinatorial libraries due to low levels of functional Ab protein. To increase the efficiency of cloning and characterization of Ab gene fragments, we have reconsidered several features of the original cloning vehicles. These studies show that at the present time a unique expression system cannot adequately accommodate the requirements of plaque-lift immunoassays for clonal selection and biochemical assays for further characterization in vitro. A monocistronic arrangement of heavy- and light-chain-encoding genes using two lacP promoters produces sufficient amounts of functional Ab protein for clonal selection from phage lambda libraries and minimizes interference with the lytic cycle of recombinant vectors. In liquid culture, a strong coliphage promoter and a relatively abundant RNA polymerase can be used to produce quantities of Ab protein sufficient for further characterization in vitro. A rapid purification protocol obviates the need for fusing heavy-chain protein to a decapeptide sequence, an affinity-tail sequence which slows the folding and assembly of the Ig heterodimer. These results have been used to formulate a new strategy for cloning and characterization of Ab gene fragments in bacteria. PMID- 8508952 TI - A bacteriophage lambda vector for the cloning and expression of immunoglobulin Fab fragments on the surface of filamentous phage. AB - We have combined the high cloning efficiency of the lambda bacteriophage vectors with the surface expression screening method for the display of combinatorial antibody fragment (Fab) libraries on the surface of filamentous phage particles. The utility of the herein described ImmunoZAP 13 system for the isolation of Fabs that specifically bind antigen is demonstrated using two phagemid display libraries prepared from a previously characterized human combinatorial library. The percentage of clones that specifically bind antigen is maintained throughout the process of subcloning the LC and VH genes into ImmunoZAP 13, in vivo mass excision to convert the lambda library to a phagemid library, and preparation of phagemid particles displaying Fabs. Specific phagemid were isolated from libraries containing 0.6% and 0.03% tetanus toxoid (TT)-binding clones after two and three rounds of biopanning, respectively. Relative binding curves determined on a small sample of isolated clones indicate that several unique immunoglobulin Fab fragments have been isolated. PMID- 8508953 TI - Trypsin display on the surface of bacteriophage. AB - The gene III and VIII-encoded coat proteins (pIII and pVIII) from bacteriophage M13 have been fused to the C terminus of the serine protease, trypsin (Tsn). The genes encoding the fusions were then inserted directly into M13mp18 to create vectors which expressed both the Tsn-coat protein hybrids and the wild-type (wt) coat proteins. Immunoblot analysis confirmed that the bacteriophage express Tsn on their surface. Isolated fusion phage possess kinetic parameters which approximate those of the wt enzyme. An endogenous Escherichia coli protease inhibitor, ecotin, copurifies with the Tsn phage. Immobilized ecotin can be used to selectively bind bacteriophage which express Tsn::pIII fusion proteins. PMID- 8508954 TI - Biochemical diversity in a phage display library of random decapeptides. AB - Detailed knowledge and understanding of the structure and function of biologically important macromolecules is frequently insufficient to permit rational, de novo design of recognition molecules and therapeutics. Traditional drug discovery has, thus, focused on screening and identifying native molecules as drugs or as templates for genetic engineering or organic synthesis. The number and novelty of lead compounds for drug discovery might be expanded significantly, however, by the ability to express and screen large libraries of peptide structures with phage display technologies [Scott and Smith, Science 249 (1990) 386-390]. The significance of such libraries as sources of novel biological ligands will depend in part on the depth and degree of biochemical diversity they comprise. We have prepared a phage display library of greater than 2 x 10(6) individual decapeptides produced as N-terminal fusions to the pIII surface protein of fd filamentous phage. The decapeptides were expressed from a degenerate DNA insert sequence that was chemically synthesized with an equal mixture of all four nucleotide bases at the three positions in each of the ten codons. Fifty-two clones were picked randomly and without prior selection from the population and the sequences of their peptide inserts were determined. Our results confirm and document the broad representation at the primary amino acid sequence level that is expected in a library expressed from random DNA inserts. More significantly, biochemical characterization shows these insert sequences correspond to structures comprising a wide range and combination of isoelectric, hydropathic, and biochemical properties necessary in drug discovery to access a significant percentage of the repertoire of possible peptide structures by affinity or activity screening. PMID- 8508955 TI - Functional display of human plasminogen-activator inhibitor 1 (PAI-1) on phages: novel perspectives for structure-function analysis by error-prone DNA synthesis. AB - The synthesis of the human plasminogen-activator inhibitor 1 (PAI-1) protein in the cytoplasm of transformed Escherichia coli cells results in inactive protein preparations that can be activated by denaturation and renaturation. We have used the phagemid pComb3, designed for combinatorial immunoglobulin repertoire cloning, for routing of PAI-1 to the periplasm and subsequent exposure on the surface of filamentous phages. Phage-displayed PAI-1 specifically binds to immobilized polyclonal and monoclonal anti-human PAI-1 antibodies. In addition, PAI-1 retains its capacity to form equimolar complexes with its target serine protease tissue-type plasminogen activator (t-PA), as well as its ability to inhibit t-PA activity. Finally, we have explored and manipulated the error-prone property of TaqI DNA polymerase during PCR amplification of the full-length PAI-1 cDNA to generate a large library of predominantly single, random PAI-1 mutants. In addition, a computer simulation program has been devised that converts the number of mutations per codogenic region (in this case PAI-1) into actual mutant proteins. The PAI-1-phage mutant library is composed of 46% single and 34% double mutants and 20% wild-type PAI-1 and can be employed to isolate mutants defective in interactions of PAI-1 with other components. The method described here is applicable to other studies on the structure-function analysis of eukaryotic proteins. PMID- 8508956 TI - A database system for handling phage library-derived sequences. AB - We have implemented a system for creating and maintaining nucleotide and amino acid sequence databases especially suited for the handling of phage library derived sequences. The system is currently used in our laboratory and has already proven to be useful for the comparison of sequences obtained by different investigators. We believe that the availability of this system will encourage and simplify the exchange of sequence data among different laboratories. PMID- 8508957 TI - M13 bacteriophage displaying disulfide-constrained microproteins. AB - A display-phage library (TN2), displaying an 18-residue peptide fused to coat protein III, represents a collection of up to 8.55 x 10(6) peptides encoded by only 1.68 x 10(7) DNA sequences. Each displayed peptide has two fixed cysteine residues (allowing disulfide formation) and six variegated residues, four between the cysteines and one either side of the cysteines. Screening this library against streptavidin (Sv) and the anti-beta-endorphin monoclonal antibody, 3-E7, yielded phage displaying disulfide-constrained microproteins with sequences similar to those published for the linear-peptide display phage. Analysis of selected clones indicated that a disulfide bond is required for high-affinity binding to each of the target proteins. The microproteins selected for binding to Sv and 3-E7 show more stringent sequence specificity than do linear peptides selected for binding to the same targets. PMID- 8508958 TI - A ribonuclease S-peptide antagonist discovered with a bacteriophage display library. AB - From a filamentous phage library displaying random hexapeptides, we selected clones displaying peptides that bind S-protein, a 104-amino-acid (aa) fragment of bovine pancreatic ribonuclease (RNase). The selected peptides show a sequence motif, (F/Y)NF(E/V)(I/V)(L/V), that bears little resemblance to S-peptide, a 20 aa fragment of RNase that is S-protein's natural ligand. One of the displayed peptides, YNFEVL, was synthesized chemically and shown by isothermal titration calorimetry to bind S-protein with a dissociation equilibrium constant of 5.5 microM at 25 degrees C, an affinity comparable to that of previously studied S peptide variants. The YNFEVL peptide is an antagonist of S-peptide, in that it blocks the ability of S-peptide to restore enzyme activity to S-protein. The S protein/S-peptide system preserves the essential features of a pharmacologically significant receptor/hormone couple, and the S-peptide antagonist can therefore be regarded as a new RNase-specific 'drug'. This work illustrates the potential value of phage display libraries for discovering novel classes of pharmaceuticals. PMID- 8508959 TI - Structural constraints on the display of foreign peptides on filamentous bacteriophages. AB - Strategies for the construction of vehicles for phage display are evaluated here on the basis of structural studies of filamentous bacteriophages. Potential sites for the insertion of foreign peptides into the major coat protein, gp8, of M13 are identified. Currently, the insertion of peptides into gp8 has two basic limitations: all insertion sites that have been used successfully are located within 5 amino acids (aa) of the N terminus, and in virions containing only mutant coat proteins, insertions larger than about 6 aa have not been successfully incorporated. The possible reasons for these limitations are discussed in terms of the structures of gp8 and the minor structural proteins, gp7 and gp9. Potential strategies for overcoming these limitations are outlined. Reasons for the successful incorporation of larger inserts into hybrid phage containing both native and mutant coat proteins are also discussed. The structures of gp6, gp7, and gp9 are described, and it is concluded that insertion sites in these minor proteins are unlikely to have substantial advantages over those currently being used in gp3. The structure of the coat protein of another filamentous phage, Pseudomonas phage Pf1, is also described. Its structure provides a number of clues for the successful design of phage display insertion sites. Because it contains a 7-aa surface loop in the major coat protein, the Pf1 coat protein may have significant advantages over gp8 of M13 as a vehicle for phage display. PMID- 8508960 TI - An M13 phage library displaying random 38-amino-acid peptides as a source of novel sequences with affinity to selected targets. AB - We have examined the potential of isolating novel ligands from a library of M13 pIII-fusion phage displaying peptides composed of 38 random amino acids (aa). The library was panned with streptavidin (SA) and a polyclonal goat antimouse IgG Fc antibody (Ab) preparation coupled to paramagnetic beads. SA selected two classes of phage from the library. One class exhibited the aa motif, HP(Q/M) theta (where theta signifies a non-polar aa), similar to the motif identified by Devlin et al. [Science 249 (1990) 404-406] using a 15-aa random peptide library displayed on phage. The other class of phage had no discernible motif. In binding experiments, the non-HP(Q/M) theta phage had a slightly higher affinity for SA than did the motif phage. Both classes of SA-binding phage failed to bind native and non glycosylated forms of avidin, even though SA and avidin are structurally similar and both proteins possess extraordinary affinities for biotin. The polyclonal goat anti-mouse IgG Fc Ab preparation selected phage displaying sequences similar to a region of the mouse IgG Fc. Thus, a single immunodominant epitope on the mouse IgG Fc was identified. Furthermore, a second phage displaying peptides with no discernible sequence similarities to mouse IgG Fc was isolated. Thus, an M13 library displaying 38-aa peptides can yield phage with affinity for various targets. Finally, we have observed a biological bias against odd numbers of Cys residues in the displayed peptides. PMID- 8508961 TI - Depression in the elderly: a treatable disorder. AB - Up to 15% of elderly women may suffer from depression. Patients with this disorder present with change in mood or diminished interest or pleasure in usual activities, as well as a variety of other neurovegetative symptoms. Depression is amenable to treatment, and a wide range of drug and nonpharmacologic modalities may be useful. The mere action of seeking professional help signals that the depressed patient has begun to take control of the situation and serves as a promising sign for recovery. The tricyclic antidepressants have a long history of use for the treatment of depression and are probably the most widely used agents for this indication, despite numerous adverse effects. Bupropion and the new selective serotonin reuptake inhibitors are effective in treating depression and are better tolerated than the tricyclics. For this reason, they may be particularly useful for treating depression in the elderly. PMID- 8508962 TI - Osteoporosis: prevention is key to management. AB - Osteoporosis is a leading cause of morbidity and mortality in elderly women. The key to managing osteoporosis is to recognize that it may be more easily prevented than treated. Preventive measures focus on increasing the peak bone mass reached in all individuals by age 20 by counseling younger patients on lifestyle habits and dietary measures that affect bone growth, and on slowing the rapid age related bone loss that occurs in postmenopausal women with the use of estrogen replacement therapy. In addition to its effects on bone, estrogen therapy also alleviates the signs and symptoms of menopause and possibly reduces the risk of death due to cardiovascular disease. A relationship between estrogens and breast cancer remains controversial, but a recent meta-analysis suggests no increased risk of this malignancy among women who receive hormone replacement therapy. PMID- 8508963 TI - Coronary artery disease in older women. AB - Despite the risk to women from heart disease, nearly all randomized, controlled studies on risk factors, treatment, and outcomes of cardiovascular disease have exclusively involved men, and extrapolation of those findings to women has resulted in several misinterpretations. More recent studies that controlled for different age and risk factors in women found that women have tended to be referred for angiography, coronary artery bypass graft surgery, and angioplasty significantly less often than men. A gender bias may contribute to the lower referral rate for women. PMID- 8508964 TI - Breast cancer: options for older patients. AB - Despite being at high risk of breast cancer, elderly women tend not to be screened systematically or treated aggressively. Elderly patients should be instructed in breast self-examination and encouraged to have annual mammograms. Biopsy options have increased and include newer techniques of needle localization, ultrasound localization, and stereotactic biopsy. Treatment options are wide-ranging, including increased emphasis on breast preservation in patients with stage I and stage II disease. PMID- 8508965 TI - Case study: the Spahl Split Vertical eruption acceleration appliance system. PMID- 8508966 TI - Mandibular whiplash. Part I: An extension flexion injury of the temporomandibular joints. PMID- 8508967 TI - A simple mode of case finishing. PMID- 8508968 TI - Orthodontic records: why? What? When? & how? PMID- 8508969 TI - Health care reform and gerontic nursing. PMID- 8508970 TI - Enhancing patient compliance: a guide for nurses. To increase their patients' compliance with health recommendations, nurses need a framework. AB - The cases studied demonstrated that an interactive patient education approach, incorporating many of the factors that influence compliance, is successful in influencing patients to follow health care advice. This approach requires a consistent, concerned, nonjudgmental, supportive relationship with the patient. Assessing each area of health behavior the patient is being asked to change, and the effects of these changes, is an essential first step. Self-care deficits, such as low self-esteem and denial, are obstacles to compliance and thus require nursing intervention. Nursing expertise in providing specific individualized information and a step-by-step plan with ample reenforcement and support is critical. Behavioral strategies are helpful for those who are unable to change with information alone. Finally, long-term nursing follow-up is essential for patient compliance. Increased compliance will save health care dollars, and nurses facilitating this are a valuable asset. Hospital nurses, home health nurses, clinic nurses, and nurses practicing in advanced practice--such as clinical specialists and nurse practitioners--would be ideal to facilitate long term follow-up. Some impact can be made by nurses no matter what the setting. PMID- 8508971 TI - The nurse as exercise leader. AB - Adherence rates to our nurse-led exercise interventions were considerably higher (88%) than those reported in the literature for overweight women of this age. Bonding between the women and the nurse leaders, as well as socialization opportunities and program design, may have contributed to this high rate. Future studies would be strengthened by comparing adherence rates of women between nurse led and non-nurse-led exercise groups. Women tested at 3 and 6 months after the intervention stated they tried many fitness clubs and spas in the area, but could find no exercise programs that were tailored to their age and fitness level or that took into consideration their individual health needs. Nurses interested and knowledgeable about changes of aging are in an ideal position to develop and lead exercise programs for older individuals, particularly those with chronic nondisabling physical problems. Nurses in this study have expanded their health promotion role by gaining knowledge and skills in exercise science. Resources available for any nurse to gain knowledge and experience about exercise are found in the resource list. PMID- 8508972 TI - The painful side of reminiscence. AB - Reminiscence has been shown to be a therapeutic activity that helps people to find meaning in their memories. Through reminiscence on past life events, the older person is able to recapture both the joy and the pain of a life story that he or she has uniquely authored. By using the nursing process, the nurse may address more effectively the painful side of reminiscence and, in so doing, help others to come to terms with unresolved life conflicts. PMID- 8508973 TI - Self-care and mentors to reduce stress and enhance administrative ability. AB - This article has considered two options available for nurses seeking career advancement in LTC. Orem's self-care model offers an approach to assist the DON to cope with stressors in the LTC setting through self-care. Mentoring also offers a strategy to assist the novice leader with professional growth. Mentoring is an emerging concept in nursing. Mentoring is of special significance in LTC because there is a shortage of DONs. Experienced DONs in LTC who have learned to handle the stresses that overwhelm the novice need to mentor younger DONs and others interested in a DON position. The use of both these strategies will increase the number of competent nurse administrators in long-term care. PMID- 8508974 TI - Gerontologic nursing: can we make it the first career choice? Managers of LTC facilities need to take a close look at how well they are meeting their employees' personal and life-style needs. PMID- 8508975 TI - Weight loss and weight gain in a nursing home: a prospective study. AB - We studied a nursing home population to delineate the frequency of weight loss and weight gain, the categories of loss and gain, and the factors or causes that contribute to losses and gains. Acute illness was determined to be the major cause of weight loss at the nursing home, followed by psychiatric/psychologic disorders and dementia. Such facts encourage replication in other nursing home populations to prompt attention to weight loss and weight gain. PMID- 8508976 TI - Support for caregivers of dependent elderly. A support group can help a dependent elderly person by helping a caregiver overcome feelings of social isolation. AB - The sharing of feelings and the sense of affiliation with and support from others was felt to be the most beneficial aspect of the group participation. Emotions described by participants included revitalization, dissipation of tension and guilt, and a renewal of their sense of identity. Attendance at the group created a social outlet that helped several members feel more socially integrated. Participants began to understand that appropriate attention to their own needs improved their outlooks and brought new energy to their role as caregivers. Nurses planning to study the impact of support groups should consider using a research design, a longitudinal design, to examine changes in caregiver stress occurring with alterations in the care receiver's illness, and to address the economic impact of support groups in reducing health care cost. PMID- 8508977 TI - Sorting out health claims for food. PMID- 8508978 TI - Update on Warfarin: special considerations for the elderly. PMID- 8508979 TI - [Value of steroid hormone receptors as prognostic factors in breast, ovarian and endometrial cancer]. PMID- 8508980 TI - [Progesterone therapy of endometrial cancer]. PMID- 8508981 TI - [The role of endocrine therapy in ovarian cancer]. PMID- 8508982 TI - [Hormone substitution in hormone sensitive neoplasms]. PMID- 8508983 TI - [Pregnancy and (pre)malignant diseases of the breast and endometrium]. PMID- 8508984 TI - [Potential tumor preventive effects of hormone preparations]. PMID- 8508985 TI - [Acute abdomen in late pregnancy: adhesion ileus]. PMID- 8508986 TI - [Diagnosis and therapy of sterility. Part III]. PMID- 8508987 TI - [Prospective, randomized study of subzonal injection with spermatozoa in cases of male subfertility]. PMID- 8508988 TI - [Comments on the contribution by P. Lemburg and his critique of the "Einbecker Recommendations of the German Society of Legal Medicine]. PMID- 8508989 TI - [Osteoporosis from the gynecologic viewpoint]. PMID- 8508990 TI - [The role of sex steroids for genesis of breast and endometrial cancer]. PMID- 8508991 TI - [Risk of injury in ice hockey: is the trend decreasing?]. AB - To date, our ongoing prospective study of more than 6 years duration has documented and analyzed 113 injuries sustained by squad players who had participated in a total of 323 international games. In the case of the upper limb, injuries to the hand and shoulder predominate (34.5%), while in the lower limb the knee joint and foot (38.9%) are most frequently involved. Despite a decrease in the number of injuries--the present incidence of injuries among senior players is 56.7%, and among junior players 59.1%--such preventive measures as checking and improving proper protective equipment must constantly be re evaluated and discussed. Today, in the case of squad players, injuries are sustained to the non-use of (full- or half-vizor helmets) or deficient equipment (modifications made in favor of comfort). In this type of team sport, speed and body contact are an integral part of the game, and this is associated with an increased risk of injury. In general terms, an important preventive measure to be demanded in national and international standardization of the player's entire equipment. PMID- 8508992 TI - [Pain syndromes of the locomotor system. Strategy and research of etiology in general practice]. AB - PROBLEM: The basis of classical medicine with its specific taxonomy for diagnoses and their etiopathogenesis was originally established by clinicians and pathologists, and has a traditional historical background. It thus also contains information as to the frequency distribution of diseases in the hospital, which often show an inverse relationship to health disorders seen in general practice. However, the fact that we have different disease statistics in general medicine gives rise to a basically different viewpoint. OBJECTIVES: Using painful conditions of the musculoskeletal system as a model, this point of view will be characterized and confirmed on the basis of the results of our own investigations into their etiology and treatment. Three questions in particular are discussed: etiological-diagnostic classification, expanded diagnostic evaluation, and applied therapy. RESULTS: In general practice, specific approaches are available for diagnosis and treatment; traditional terms employed in the hospital context cannot simply be applied or taken over unmodified. PMID- 8508993 TI - [Peripheral arterial occlusive disease--initial therapy in general practice]. PMID- 8508994 TI - [Suspected occlusive jaundice--diagnostic process]. PMID- 8508995 TI - [Sodium and water imbalance in liver cirrhosis. Clinical aspects, pathogenesis and therapeutic consequences]. PMID- 8508996 TI - [A one year study of single administration of nilvadipine. Results of the effectiveness and long-term tolerance in hypertension]. AB - AIM: To test the efficacy and long-term tolerability of a single daily dose of nilvadipine. STUDY DESIGN: Open, multicenter follow-up study of 8-months duration following a 4-month randomized double-blind preliminary study (vs. nifedipine). PATIENTS: 307 ambulatory hypertensives with a diastolic blood pressure of < or = 95 mm Hg at the end of the preliminary study. MEDICATION: One capsule of nilvadipine retard 8 or 16 mg taken once a day (in the morning). PARAMETERS: Monthly recording of blood pressure, pulse rate and body weight, and any adverse reactions: global assessment by the physician of tolerability and efficacy in month 12; in addition, ECG and laboratory parameters in months 6, 9 and 12. RESULTS: In more than 95% of the patients, nilvadipine reduced blood pressure to normal levels. Some 95% of the physicians investigated assessed efficacy and tolerability to be "good" to "very good". The direct changeover of medication from nifedipine t.i.d. to a single daily dose of nilvadipine presented no problems. PMID- 8508997 TI - [Rational diagnosis of thyroid gland diseases]. AB - The recommendations for the diagnosis of diseases of the thyroid gland issued seven years ago by the Thyroid Gland Section of the German Society of Endocrinology continue to apply, and are still relevant. On this basis, the main procedures available for effective and rational diagnostic evaluation are discussed. Depending upon the case history and clinical findings, a diagnostic strategy is developed for the most common benign diseases of the thyroid gland. PMID- 8508998 TI - [Poliomyelitis in the Netherlands: consequences for travelers from Germany?]. PMID- 8508999 TI - [Obstructive jaundice--therapeutic procedure]. PMID- 8509000 TI - [Topical therapy of onychomycoses with 8% ciclopirox laquer. An open, non comparative study]. AB - AIM: To investigate the efficacy and tolerability of 8% Ciclopirox-containing nail varnish used for topical treatment of onychomycoses in an open single-center study. METHOD: Forty-seven patients with onychomycoses affecting a finger and/or toe nail were treated with nail varnish containing Ciclopirox once daily for 6 months. The results of treatment were monitored at regular intervals during treatment, and for 6 months after termination of therapy. RESULTS: By the end of treatment, culture for fungi was negative in all the patients investigated; clinical healing was observed in 26 patients (56.5%) and clinical improvement in 13 (28%). In seven patients, however, the clinical findings had hardly changed. By the end of the 6-month follow-up phase, the healing rate (mycological and clinical) was 59.5% (28/47 patients), improvement (mycological healing, clinical improvement) was 12.8% (6/47 patients) and failures (neither mycological nor clinical healing) was 27.7% (13/47 patients). Mild distal subungual onychomycoses and superficial white onychomycoses are the main indications for topical antimycotic treatment. In contrast, extensive distal subungual nail mycoses, proximal subungual and total dystrophic onychomycoses in which the matrix of the nail already appears to be involved, represents the limitations of topical treatment. In addition to the high level of efficacy, which depends upon the extent and form of nail involvement, the substance was very well tolerated; in none of the patients were any side effects observed. PMID- 8509001 TI - [Abdominal complaints--always consider salmonellosis!]. PMID- 8509002 TI - [Preventive antimycotic short-term therapy for patients at risk. Treatment of dermatomycoses in general practice: 3. Differential therapy. Interview by T.U. Keil]. PMID- 8509003 TI - [Gallstone dyspepsia--a myth?]. AB - Gallstones accompanied by dyspeptic symptoms, were long not considered to be silent. The complaints were thought to be caused by the gallstones, and were termed gallstone dyspepsia. Up to 47% of all cholecystectomies are performed for dyspeptic symptoms. Numerous control studies have, however, all demonstrated that dyspeptic symptoms in stone carriers and controls with no gallstones occur with equally frequency, and that it is not possible to differentiate gallstone specific dyspepsia. The frequent concomitance of dyspepsia and gallstones, is coincidental, and there is no causality involved. Thus, gallstones accompanied by dyspepsia must be considered silent stones. Not the silent gallstone, but gallstone dyspepsia is the myth. PMID- 8509004 TI - [Carbon dioxide--contrast medium for digital subtraction angiography]. AB - Fundamental considerations: Despite appreciable improvements in conventional iodine-containing contrast media, vascular studies involving patients with renal insufficiency, hyperthyroidism or known allergic reaction to conventional contrast media continue to pose a problem. Own study: Testing the investigation of the possibility of visualizing vessels using carbon dioxide as a gaseous contrast medium. In 30 patients, angiography of the pelvis and legs (DSA) employing conventional iodine-containing media and/or CO2 were carried out simultaneously. RESULTS, handling and toleration were compared. In two further patients, percutaneous transluminal angioplasty and stent implantation, respectively, were successfully performed under CO2 control. RESULTS: All the findings obtained with "normal" DSA were also obtainable with CO2. The CO2 examination, however, was often plagued by incomplete contrasting of the blood vessels, with interruption of the contrast medium column, which made assessment more difficult. In two of the 30 patients undergoing angiography of the pelvis and legs, the investigation had to be abandoned on account of persistent intensive lower abdominal pain under CO2 injection. PMID- 8509005 TI - [Granulocyte hypersensitivity reactions in hemodialysis treatment]. PMID- 8509006 TI - [New guidelines for fracture treatment. Part 8: Ambulatory after-care--early measures and follow-up]. PMID- 8509007 TI - [Characteristics of antibiotic therapy in the elderly]. AB - In the elderly, the morbidity and mortality rates of infections are significantly increased. Atypical or nonspecific symptoms or their absence often delay the diagnosis. When providing treatment, in addition to microbiological specifics of infections in the aged, consideration must also be given to pharmacokinetic aspects when choosing a suitable antibiotic. Furthermore, any existing medication must be taken into account in order to avoid interactions and undesirable drug effects. In view of the elevated mortality and multimorbidity rates, the early use of antibiotics is of considerable importance. If no specific etiological diagnosis is available, a broad-spectrum antibiotic should be administered. PMID- 8509008 TI - [Captopril and hydrochlorothiazide. Advantages of their synergistic effect]. PMID- 8509009 TI - [Reference tables of WHO Chapter V (F) of the 10th revision of the International Classification of Diseases (ICD-10): ICD-9 vs. ICD-10]. AB - With Chapter V of the Tenth Revision of the International Classification of Disease (ICD-10), the World Health Organization introduces a new classificatory approach. This instrument, which differs considerably from ICD-9, follows the principle of operational diagnosis introducing psychopathological, time- and course-related diagnostic criteria for the first time in the development of the ICD-system. Following a descriptive approach, the differentiation between psychosis and neurosis has been abandoned with the consequence of classifying the corresponding disorders under different diagnostic terms. To ensure the applicability of the new classificatory system, additional documents were developed by the Department of Mental Health of WHO. The WHO-Crosswalks, which were translated and adapted for the conditions in German-speaking countries by the authors, will provide a help concerning the classification of ICD-9 categories within ICD-10. Each diagnostic category of ICD-9 is compared with the corresponding categories in ICD-10 including a critical comment in the text. PMID- 8509010 TI - [Reference tables of WHO Chapter V (F) of the 10th revision of the International Classification of Diseases (ICD-10): ICD-10 vs. ICD-9]. AB - The introduction of ICD-10, Chapter V (F) will have the consequence of a changed diagnostic spectrum and a revision of several diagnostic terms including a differentiation of several diagnostic categories. Several diagnostic categories of ICD-10 have no corresponding terms in ICD-9. Conversely, many diagnostic categories in ICD-9 are covered by several diagnostic categories in ICD-10 following phenomenological aspects as an organizing principle. Against this background the Department of Mental Health of the World Health Organization developed crosswalks between the two systems. The WHO-Crosswalks, which were translated and adapted for the conditions in German-speaking countries by the authors, will provide a help concerning the classification of ICD-9 categories within ICD-10. Each diagnostic category of ICD-9 is compared with the corresponding categories in ICD-10 including a critical comment in the text. PMID- 8509011 TI - [Conflict regarding neurology--a study of specialty origin of clinical neurology in Germany]. AB - Although Germany was a center of neurological research during the 19th century institutionalisation of clinical neurology was delayed in comparison to other countries. The establishment of neurology in Germany is characterised by a conflict between internists, psychiatrists and neurologists that lasted nearly a hundred years. The present study describes and analyses the motives and the course of development of this dispute. The conflict could not be solved by means of objective arguments because on the one hand nervous disease were part of internal medicine, while on the other hand the postulated identity of mental and nervous disease was the central paradigm of the academic psychiatrists. As a professional group the entry of the neurologists into the dispute was very late at a time point when the historical development was already in favour of the psychiatrists. By taking into account not only intrascientific but also political and economic factors, the dynamics of the historical process becomes comprehensible. PMID- 8509012 TI - Health insurance and the elderly. AB - The effectiveness of proposed changes to the Medicare program depends on consumers' responses to different market incentives, which vary according to the coverage the elderly possess to supplement their Medicare coverage. This Data Watch explores the extent of supplemental insurance among the elderly, based on a new data set from the Medicare Current Beneficiary Survey. Only 11 percent of Medicare beneficiaries have only Medicare as their source of coverage; the rest of the elderly population is covered by either private coverage (employer sponsored retiree coverage or individually purchased coverage) or Medicaid. An increase in Medicare cost sharing would likely affect one-third of elderly beneficiaries, which calls into question the effectiveness of this approach to Medicare program reform. PMID- 8509013 TI - The effects of aging and population growth on health care costs. AB - Aging and population growth both contribute importantly to the rise in health care costs. However, the percentage contribution of these factors declined between 1970 and 1990, and we expect a continued decline through 2005. Data indicate that the relative costs of treating patients age sixty-five and over grew more rapidly than did the costs of treating other patients. Sensitivity analyses indicate that regardless of whether these trends persist, the percentage contribution of aging and demography is likely to decline between 1990 and 2005. Application of our model through 2030 suggests that if current trends persist, aging will cause a major acceleration in the rise in costs. PMID- 8509014 TI - More than loose change: household health spending in the United States and Canada. AB - A key point of comparison between U.S. and Canadian health spending is what amount citizens spend for health coverage, given their respective health systems. A comparison of household spending surveys in the two countries shows that Canadian households pay about half of what American households pay for health coverage, but their personal tax burden is almost twice that of Americans. Net personal consumption thus is quite similar between the two countries. Total household health spending in the United States amounted to $215.6 billion in 1989 -one-third of the total spent on health that year. PMID- 8509015 TI - Medicaid beneficiaries and health reform. AB - Some health reform proposals include reductions in Medicaid benefits in favor of a more basic health plan that would cover a broader range of Americans, including the uninsured. This study provides data on the implications of such proposals. With current Medicaid coverage, the study finds that one in five adults experienced serious problems getting and paying for health care in the past year. In addition, a substantial number of Medicaid beneficiaries now have trouble paying for the basic necessities of life; the well-being of these beneficiaries (between one-quarter and one-half of all beneficiaries) would be placed in jeopardy by proposed cuts in coverage levels and benefits. Medicaid beneficiaries report worse health status and greater disability level than the general public, suggesting that proposals to link Medicaid coverage with ability to work should be pursued with caution. PMID- 8509016 TI - State estimates of uninsured children. AB - About twelve million American children lack health insurance. Attempts to assess the effectiveness of Medicaid expansions and other reforms are hampered by the lack of reliable state-level data on this population. This DataWatch presents baseline statistics on the insurance status of children, based on the Current Population Surveys from 1988, 1989, and 1990. The study finds the sharpest increase in uninsured rates from 1987 to 1989 among middle-class children and among children ages seven to twenty-one, suggesting that expanding Medicaid will fail to reach a large portion of the population at greatest risk. PMID- 8509017 TI - A program to support small rural hospitals. AB - Rural hospitals continue to face the threat of closure. Congress passed legislation in 1989 and 1990 to offer an alternative for small rural hospitals; the legislation encourages hospitals to form networks comprising an essential access community hospital (EACH) and one or more rural primary care hospitals. This legislation is a tightly focused program that will affect no more than an estimated 150 hospitals in seven states; implementation of the program has been controversial, as this DataWatch demonstrates. The authors describe the profile of rural hospitals that are likely to apply to participate in the program, based on distances between hospitals and number of beds. PMID- 8509019 TI - The microanatomy of health care. PMID- 8509018 TI - Impact of socioeconomic status on hospital use in New York City. AB - This DataWatch examines the potential impact of socioeconomic differences on rates of hospitalization, based on patterns of hospital use in New York City in 1988. The research suggests that lack of timely and effective outpatient care may lead to higher hospitalization rates in low-income areas. For certain conditions identified as ambulatory care sensitive, hospitalization rates were higher in low income areas than they were in higher-income areas where appropriate outpatient care was more readily available. Further study is needed to determine the relative impact of various economic, structural, and cultural factors that affect access to care. PMID- 8509020 TI - Waivers, research, and health system reform. PMID- 8509021 TI - New rules and roles for states. PMID- 8509022 TI - Articulating the need for innovation and accountability. PMID- 8509023 TI - Developing AIDS community service consortia. PMID- 8509024 TI - Responding to California's perinatal access crisis. PMID- 8509025 TI - Income-related cost sharing in health insurance. AB - The vast majority of health plans in the United States require patients to meet cost-sharing requirements that are unrelated to income. Because this is highly inequitable, the authors propose a new system in which cost sharing is explicitly linked to income levels. This proposal differs from earlier proposals to relate cost sharing to income, which relied on the federal income tax system. In this plan, employers and insurers (both public and private) would collect the information necessary to relate cost sharing amounts to income. The proposal could be applied to nearly any health system reform proposal currently under discussion. The authors examine the experience of a number of U.S. firms that have already incorporated income-related cost sharing, as possible models to apply to health insurance nationwide. PMID- 8509026 TI - Health policy and the courts: judicial or political failure? PMID- 8509027 TI - A new dimension to health policy and the courts. PMID- 8509028 TI - Involving consumers and families in mental health policy. PMID- 8509029 TI - Changing substance abuse treatment. PMID- 8509030 TI - Health care reform and people with disabilities. AB - As a group, people with disabilities or chronic conditions experience higher-than average health care costs and have difficulty gaining access to affordable private health insurance coverage. While the Americans with Disabilities Act will enhance access by prohibiting differential treatment without sound actuarial justification, it will not guarantee equal access for people in impairment groups with high utilization rates. Health care reform is needed to subsidize the coverage of such individuals. Such subsidization can be achieved under either a casualty insurance model, in which premiums based on expected costs are subsidized directly, or a social insurance model, in which low-cost enrollees cross-subsidize high-cost enrollees. Cost containment provisions that focus on the provider, such as global budgeting and managed competition, will adversely affect disabled people if providers do not have adequate incentives to meet these people's needs. Provisions focusing on the consumer, such as cost sharing, case management, and benefit reductions, will adversely affect disabled people if they unduly limit needed services or impose a disproportionate financial burden on disabled people. PMID- 8509031 TI - Cost-effective health care: the Rochester experience. AB - Rochester, New York, has been cited repeatedly for having achieved one of the most cost-effective and efficient health care systems in the country. The determinants of the success of this system include a long history of comprehensive health planning; innovative hospital reimbursement programs; community-rated health insurance; and high levels of mutual cooperation among business, insurers, hospitals, and physicians. The Rochester system promotes the goals of access, quality, affordability, and provider satisfaction through a balanced approach to regulation and competition. PMID- 8509032 TI - States in a reformed health system: lessons from nursing home policy. AB - Most serious health system reform proposals include a prominent role for states, despite documented variation in costs, delivery systems, and health status among states. As policymakers search for an approach that will reform the health system and minimize inappropriate interstate variation, the experience of nursing home policies and politics in two states--New York and California--can offer useful lessons about underlying reasons for variation and how to ensure equitability amidst state differences. These two states are examined as case studies because they have the nation's two largest Medicaid programs yet have approached their long-term care systems very differently. The differences in their nursing home policy approaches suggest that state-based health system reform be pursued with caution, lacking further study of state variations. PMID- 8509033 TI - Competition versus regulation: its effect on hospitals. AB - While factors other than competition and regulation influence hospital's behavior, these two strategies have dominated the health policy debate. To examine the impact of these two competing strategies on patients and hospitals, the authors examine experiences in Baltimore, which has followed a regulatory strategy since the early 1970s, and Minneapolis/St. Paul, which has pursued a competitive strategy during the same time frame. Compared with the national average, both strategies had only a minor impact on containing hospital costs per capita, but they influenced hospital productivity, cost per discharge, and utilization in different ways. PMID- 8509034 TI - Government and the competitive marketplace. PMID- 8509035 TI - Academic medical centers and managed care: uneasy partners. PMID- 8509036 TI - National health care spending in 1991. AB - The United States spent $751.8 billion on health in 1991, an increase of 11.4 percent over 1990 levels. National health expenditures consumed 13.2 percent of gross domestic product (GDP). The 11.4 percent growth rate in spending is four times the rate of growth in the general economy. Medicaid contributed substantially to overall spending in 1991. Consumers' out-of-pocket payments grew only 5.7 percent to a total of $144.3 billion, accounting for 19.2 percent of national health expenditures (the lowest share ever reported). Economywide price inflation accounted for 36 percent of health spending growth in 1991; increases in use and intensity of health services accounted for 30 percent of total spending growth; excess medical price inflation accounted for 25 percent, an amount that is consistent with its share throughout the 1980s. PMID- 8509037 TI - Extended total gastrectomy for carcinoma of the cardia. AB - Eighty-five patients with gastric carcinoma developing at or involving the cardia were operated on under a newly established principle to prevent a cancer-positive proximal margin. The choice of operative procedure, standard total gastrectomy or extended total gastrectomy, was determined by the degree of proximal extension of carcinoma as confirmed by preoperative examinations. The cancer-positive rate was decreased in this manner to 1.2% from the 13.8% of the controls operated on before the principle was established. Extended total gastrectomy without sternotomy should be used more frequently than that with sternotomy because of the technical advantages. Survival rates of the 85 patients were 48.3% at three years and 30.4% at five years after the operation, and were not significantly different from the controls. As post-operative survival rate is influenced by factors other than transmural extension of the tumor, this study should prompt us to focus on the problem of the proximal surgical margin in surgery for carcinoma of the gastric cardia. PMID- 8509038 TI - Gastric polypoid lesions--an eight-year study. AB - We have reviewed the eight years of experience with gastric polypoid lesions of a university hospital serving the Tel Aviv area, and analyzed 188 polyps. No clinical or endoscopic findings were able to distinguish the polyp variants prior to histological examination. The most frequent type of polyp was the hyperplastic polyp (45.2%), followed by the inflammatory type (29.3%). There were six cases of adenoma and ten cases of gastric carcinoma. The polyps were distributed equally within the body (44.7%) and antrum (48.9%), while the fundus was rarely involved (6.3%). Our findings are compatible with the statement that in general there is no distinction between the histological types classified by sex, age, location, symptoms or endoscopic appearance. Nevertheless, this is the first report of a higher incidence of gastric polyps among Ashkenazi Jews than non-Ashkenazi Jews with identical sex distribution. PMID- 8509039 TI - Cytoprotective drugs in the prevention of ethanol-induced experimental gastric mucosal damage: a morphological study. AB - Various so-called "cytoprotective" agents (sucralfate, carbenoxolone, 16,16 dimethyl-PGE2, sulglycotide and Maalox TC) have been tested on rats, with the aim of quantifying their capability to prevent ethanol-induced gastric mucosal damage. Rats fasted for 48 hours received 1 ml of 80% ethanol by oral gavage, after prior oral treatment with placebo or one of the above-mentioned drugs u.i.d. for 5 consecutive days. Six hours after ethanol administration, the animals were sacrificed and the stomach was removed and processed for computerized macroscopic assessment of the damaged surface and for structural (light microscopy) and ultrastructural (scanning and transmission electron microscopy) studies. The results obtained demonstrate that ethanol injury caused extensive mucosal necrosis of the glandular region of the stomach, an event that was effectively reduced in rats treated with 16,16-dm-PGE2, carbenoxolone or sulglycotide. These drugs appeared to preserve the mucosa, with morphology comparable to that of normal noninjured rats - in contrast to the other drugs investigated. These data confirm the cytoprotective properties of sulglycotide in particular, which was the most potent agent for preventing the development of ethanol-induced acute lesions of the gastric mucosa. PMID- 8509040 TI - Lymphocytes from patients with chronic duodenal ulcer disease show enhanced proliferative response to beta-endorphin. AB - We investigated the effect of phytohemagglutinin and the neuropeptide beta endorphin on the in vitro lymphocyte proliferative response in patients with chronic ulcer disease and upper gastrointestinal bleeding or in remission, acute ulcer or hemorrhagic gastritis, and in healthy persons without upper gastrointestinal disease. We found that the addition of beta-endorphin produced a strongly enhanced proliferative response to phytohemagglutinin in lymphocytes from patients with chronic ulcer disease, and in particular from those with recent bleeding. PMID- 8509041 TI - Results of bilio-digestive derivative surgical procedures for benign lesions. AB - Short and long term results of 52 derivative-surgical procedures (43 choledocho duodenal and 9 hepatico-jejunal with 45 latero-lateral and 7 termino-lateral approaches) were examined. The procedures were performed on patients with benign bilio-digestive conditions: 46 cases of lithiasis, 2 of which were sump syndromes after latero-lateral derivations, and 6 cases of chronic pancreatitis. Several patients were in poor pre-operative condition, which may have influenced postoperative mortality rates (6%). Morbidity was 15 per cent. Four patients (8%) without anastomotic stenosis had infections of the hepatobiliary system within four years of choledochoduodenostomy. In some cases of benign bilio-digestive lesions, derivative surgery is the procedure of choice, being preferable to endoscopic sphincterotomy. In derivative surgery, a termino-lateral approach has better results than a latero-lateral approach. Furthermore, due to the risk of stasis following a choledochoduodenostomy, a hepaticojejunostomy may be preferable. PMID- 8509042 TI - Extracorporeal immunopharmacotherapy in patients with chronic septic cholangitis. AB - An immunological examination of patients with septic cholangitis revealed secondary immunodeficiency. Traditional methods of therapy and immunocorrection were ineffective in eight patients with septic cholangitis. They were treated with extracorporeal immunopharmacotherapy using diuciphon. For the accomplishing detoxication, this was used in combination with plasma exchange. The course of treatment consisted of 3 or 4 procedures, within a 3- or 4-day interval. As a result of extracorporeal immunocorrection, patients were observed to have positive immunological indexes, demonstrated by the normalization of the lymphocyte count in 5 of 6 patients, CD3+ and CD4+ in 3 patients, and CD8+ in 4. Four patients had clinical remissions (0.5 year), and 3 patients underwent surgery with no septic postoperative complications. PMID- 8509043 TI - CT-scan diagnosis of bilateral obturator hernias in a patient with chronic chylous ascites. AB - Bilateral obturator hernias were diagnosed in a 61-year-old woman by CT-scan examination, permitting an elective surgical repair by preperitoneal interposition of Teflon mesh. The condition developed in a patient presenting with a 15-year history of chylous ascites, occasioned by primary hypoplasia of the lymphatic system and cirrhosis of the liver. PMID- 8509044 TI - Surgical treatment of congenital dilatation of the biliary system. AB - Six out of 1,612 patients operated on for biliary diseases between January 1974 and January 1985, had Caroli's disease. A summary of the clinical records is included. The treatment performed was: external drainage in a patient with sepsis, who did not improve and died; left hepatic lobectomy and biliary-jejunal diversion in two patients; right extended lobectomy in one patient; distal spleno renal shunt in a patient with severe biliary cirrhosis and recurrent hemorrhage from esophageal varices. The last patient suffered from a combination of a choledochal cyst and dilatation of the left intrahepatic branches, and underwent complete resection of the choledochal cyst, and biliary jejunal anastomosis on a porta-hepatis using a Roux-en-Y jejunal loop. Currently, five patients are recovering and are free of symptoms. The authors discuss the indications for liver resection and resection of a choledochal cyst. PMID- 8509045 TI - Diagnostic and therapeutic interventions in post-laparoscopic cholecystectomy biliary complications. AB - Radiological imaging and therapeutic interventions were performed in eight patients with biliary complications following laparoscopic cholecystectomy. The diagnostic approach and the outcome of the therapeutic procedures were evaluated. Complications observed were bile leakage from the cystic duct stump (n = 2); erroneous identification of the cystic duct leading to common hepatic duct transection (n = 1) and hepatic duct ligation (n = 2); liver abscess (n = 1); and retained common duct stones (n = 2). Diagnostic ultrasonography is capable of detecting the presence of abnormal fluid collection and the diameter of the common duct with or without the presence of a stone, although bile leaks and retained common duct stones can only be demonstrated by either endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. Once a bile leak had been confirmed, therapeutic endoscopic biliary stenting was successfully applied in one patient while the other received percutaneous transhepatic biliary drainage. Definitive diagnosis of retained common duct stone was established by endoscopic retrograde cholangiopancreatography, and immediate endoscopic sphincterotomy with stone extraction was performed. Follow-up radiological imaging was done to determine the effectiveness of the therapeutic procedures applied in each patient. All our patients improved clinically, and further surgical intervention was not needed. PMID- 8509046 TI - Pancreatic ascites. AB - Pancreatic ascites is the accumulation of high protein, amylase-rich intraperitoneal fluid which occurs during the course of chronic pancreatitis, in association with rupture of a pseudocyst or disruption of a pancreatic duct. This is an uncommon complication, with less than 250 cases reported in the literature. We have treated 6 patients with pancreatic ascites. Five were males with a history of chronic alcoholism, but no known pancreatic disease. The diagnosis was made by ascitic tap and the site of the leakage identified by ERCP. Treatment was initiated with total parenteral nutrition in all cases. In 5 patients, the ascites failed to respond to medical therapy. Surgical intervention was indicted in 3 of these patients. The diagnosis of pancreatic ascites should be considered in patients with refractory ascites, and a combination of medical care and judicious surgery have contributed to an improved outcome. PMID- 8509047 TI - Extracorporeal shockwave lithotripsy for treatment of intrahepatic stones: in vitro and in vivo studies. AB - In vitro, bile duct stones, mostly comprising calcium bilirubinate, are readily fragmented by extracorporeal shockwave lithotripsy (ESWL). In the case of intrahepatic stones, ESWL is effective if the stones float freely in the bile, but if the stones completely fill, or are impacted within, the hepatic duct or bile duct, attempts at fragmentation will end in failure. Three patients with intrahepatic stones were treated with ESWL, and effectively fragmented. The stone fragments passed out spontaneously through T-tube sinus tract, PTDC sinus tract and the sphincter of Oddi as shown in the second cholangiogram. No specific complication was noted in our experimental and clinical experience. We believe that ESWL for fragmentation of biliary stones is technically reliable. The problem of the passage of these fragmented stones is considered; if necessary, it can be overcome by endoscopic means. PMID- 8509048 TI - Non-specific immunological abnormalities and association of autoimmune diseases in idiopathic portal hypertension. A study by questionnaire. AB - A large survey by questionnaire of idiopathic portal hypertension (IPH) in Japan disclosed that 11.9% of 160 cases were associated with one or two autoimmune diseases, and 26.3% of them disclosed hypergammaglobulinemia. Patients with IPH also frequently showed one or more autoantibodies in the serum, such as antinuclear or anti-smooth muscle antibodies. These findings overlapped frequently in the same patient. These data imply that immunological disturbance and/or chronic antigenic stimulation are related to the pathogenesis of IPH, though the exact immunological mechanisms remain unclear. It will be necessary to study more specific immunological reactions in IPH. PMID- 8509049 TI - Disseminated intravascular coagulation (DIC) in the intestinal circulation by acute portal vein occlusion and the effectiveness of portal-venous bypass using an antithrombogenic catheter. AB - The changes in blood coagulation/fibrinolysis and intestinal microvasculature after acute portal vein occlusion were studied in adult mongrel dogs. All five dogs that underwent portal vein ligation with resultant portal system thrombosis died within 81-130 min following the procedure. Fibrin deposition occurred in the small-intestine mucous-membrane capillaries within 10 min after ligation. Before ligation, high levels of tissue plasminogen activator activity were noted in small vessels, mainly those of the small-intestine submucosa. However, this activity decreased significantly after portal vein ligation, suggesting progression into irreversible disseminated intravascular coagulation. After simultaneous portal vein and superior mesenteric artery occlusion, similar changes occurred, but later than with portal vein ligation alone. The five dogs who underwent this procedure died within 70-195 min. However, if portal blood was bypassed into the femoral vein through an anti-thrombogenic heparinized hydrophilic catheter, deterioration after complete portal vein ligation was not observed; the five dogs that underwent this procedure survived. PMID- 8509050 TI - Endoscopic intravascular esophageal pressure measurements in cirrhotic patients: response to metoclopramide. AB - This study reports the effects of metoclopramide (10 mg i.v.) on intravascular esophageal variceal pressure in 12 patients with alcoholic cirrhosis. The esophageal variceal pressure was measured by the direct variceal puncture technique. Metoclopramide caused a reduction in the variceal pressure in 10 out of 12 patients; overall, there was a decrease from 21.5 +/- 5.0 mmHg to 14.0 +/- 3.4 mmHg (p < 0.001). In conclusion, intravenous metoclopramide, which increases lower esophageal sphincter pressure, significantly decreases intravascular variceal pressure in cirrhotic patients. PMID- 8509051 TI - Complications following major abdominal surgery in cirrhotic patients. AB - The morbidity and mortality associated with major abdominal surgical interventions in 34 histologically proven cirrhotic patients are analyzed by the authors. The surgical interventions were carried out as urgent, absolute and elective indications. Thirty-seven general and surgical complications were observed following major abdominal surgery in 34 cirrhotics. Seven out of 34 patients died, giving a mortality rate of 21%. Suture-line insufficiency, peritonitis, sepsis and other inflammatory processes turned out to be the most common complications. Statistical analysis showed that the Child criteria, prothrombin level and white blood cell count were useful prognostic factors. PMID- 8509052 TI - Schistosomiasis and vascular alterations of the colonic mucosa. AB - The diagnosis of schistosomiasis is made by identification of Schistosoma in stool and urine, or by colonic or hepatic biopsies. The authors demonstrate in this paper, however, that it is also possible to suspect this disease by colonoscopy, i.e., by macroscopic observation of the vascular alterations in the mucous membrane of parasite infected patients. Out of 33 patients -21 with schistosomiasis and 12 with other intestinal parasitoses--the endoscopist correctly diagnosed Schistosomiasis in 18 (85.7%) patients, although he had no previous experience of the diagnosis. Since this infection is widespread throughout the world, these endoscopic findings are important; they may help the physician correctly diagnosis schistosomiasis in non-endemic areas where the diagnosis may not be suspected. PMID- 8509053 TI - Toxic megacolon secondary to acute ischemic colitis. AB - A 72-year-old woman without significant medical history was admitted with abdominal pain, high fever, leukocytosis, bloody diarrhea and marked dilation of the transverse, descending and sigmoid colon. Toxic megacolon was diagnosed and responded well to medical treatment. Seven weeks after her admission, however, the patient developed a stenotic lesion in the sigmoid colon. The lesion was managed surgically. Histological examination of the resected colon revealed resolving ischemic colitis affecting only part of the thickness of the intestinal wall. The patient has been healthy since the surgery, i.e., for two years. PMID- 8509054 TI - Fecal occult blood testing: comparative evaluation of a two-hole versus a three hole single slide test. AB - The aim of this study was to analyze the effectiveness of the three-hole fecal occult blood test hemoCARE in the detection of colorectal neoplasia in asymptomatic individuals in comparison with the conventional two-hole single slide test Hemoccult. Tests were distributed to 10,269 subjects older than 45 years. A total of 62.8% of the participants returned both tests, which were positive in 374 (5.8%). The diagnostic evaluation of 208 cases revealed 57 colorectal adenomas and carcinomas. The hemoCARE test was associated with a larger number of false-positive results than the Hemoccult test (p < 0.01). Fecal occult blood testing with the three-hole test demonstrated a significant increase in the yield of colorectal neoplasms as compared with the two-hole test (57 vs. 48 detected colorectal neoplasms; p < 0.01) without modifying the positive predictive value. PMID- 8509055 TI - Congenital stricture of the common hepatic duct due to a web: an unusual case without jaundice. AB - In adults, congenital stricture of the common hepatic duct that does not cause jaundice is very rare. In this report we present a case of a congenital web occluding the common hepatic duct at the level of the bifurcation that was diagnosed by endoscopic retrograde cholangiography. PMID- 8509056 TI - A case of type 3 choledochal cyst masquerading as acute abdominal pain. AB - A type 3 choledochal cyst, presenting with acute abdominal pain attacks, was diagnosed in a 24-year-old man. Previously he had undergone exploratory laparotomy for acute abdominal pain, which had proved negative. An internal drainage procedure was chosen as the surgical procedure. The patient is under constant follow-up because of the risk of a malignancy developing. PMID- 8509057 TI - [Clinical studies on multiple sclerosis]. PMID- 8509058 TI - [Innervation of the pineal gland and its significance]. PMID- 8509059 TI - [A clinical and basic study of postoperative cholestasis]. PMID- 8509060 TI - [A 20 year experience in community medical care: ophthalmologic check up of school children and premature infants]. PMID- 8509061 TI - [Immunohistochemical studies on expression of epidermal growth factor receptor (EGFR) and proliferative activity in human colorectal cancers]. AB - Expressions of epidermal growth factor receptor (EGFR) were studied immunohistochemically in a total of 101 human colorectal cancers, and compared with clinicopathological findings. DNA polymerase alpha, a marker of the proliferating cells, was stained immunohistochemically in 26 cases in which fresh and frozen sections were obtained, and growth fraction was calculated as labeling index. EGFR positive tumor cells were detected in 17 cases (16.8%) of the 101 colorectal cancers. Significantly high incidence of EGFR expression was observed in more deeply invasive tumors, larger tumor sizes and more infiltrating macroscopic types. No significant differences, however, were observed between EGFR-positive and EFGR-negative cases regarding lymphnode metastasis, histopathological classification and pathological staging. DNA polymerase alpha laveling index was 597.9 +/- 76.6, and 428.4 +/- 140.2 in EGFR-positive cases, and EGFR-negative cases, respectively. There was a significant (p < 0.01) correlation between DNA polymerase alpha labeling index and EGFR status. These results indicate that EGFR positive cases in colorectal cancers have higher proliferative activity and more invasive stage, compared with EGFR negative cases, and suggest that EGFR produced by tumor cells play an important role in the progression and proliferation of colorectal cancers. PMID- 8509062 TI - [Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat]. AB - Kindling model has been regarded as an experimental model for partial seizure with secondary generalized convulsion in human epilepsy. A number of pharmacological studies have been carried out to evaluate antiepileptic effects of conventional anticonvulsants on kindled seizures, mainly using amygdala kindled model. However, it is known that hippocampus is a more important site for human temporal epilepsy. It should therefore be considered appropriate to evaluate effects of antiepileptic drugs, not only on amygdaloid- but also on hippocampal-kindled seizures. In the present study, effects of chronically administered phenobarbital (PB) on amygdaloid- and hippocampal-kindled seizures were investigated. In the first session, cats were orally administered 6 mg/kg of PB for 15 days to obtain the serum level between 15 micrograms/ml and 25 micrograms/ml (optimal level for human epileptic seizure), then stimulation was carried out once a day for the following five days with suprathreshold stimulation intensity (100 microA higher than generalized seizure triggering threshold). For evaluation of drug efficacy, duration of afterdischarge and seizure severity were determined. After the end of session 1, session 2 started with 12 mg/kg of PB for 35-50 micrograms/ml serum level (subtoxic level) and continued in the same manner as stated above. PB was proved to be more effective for hippocampal- than for amygdaloid-kindled seizures. Generalized convulsions were easily suppressed in the level of 15-25 micrograms/ml and afterdischarge was totally suppressed in 33% of cats in the level of 35-50 micrograms/ml in the hippocampal-kindled group. However, amygdaloid-kindled seizures were more resistant to PB. It was difficult to suppress generalized convulsion in the level of 15-25 micrograms/ml, and total suppression of afterdischarge was extremely rare even in the higher serum level in amygdaloid-kindled cats. In addition, cats requiring a smaller number of stimuli to the completion of kindling tended to show more marked drug-resistance. Such tendency could be seen in both groups, although, more distinct in amygdaloid-kindled cats. Also evaluated were effects of PB on the secondary site kindled-seizures and it was shown that the potency of PB was less manifest in secondary site amygdaloid seizures than in primary site hippocampal seizures. These data show that the drug efficacy in the kindling model depends on the stimulated brain region as well as animals predisposition probably related to rapid acquisition of epileptogenesis. The intractability of temporal lobe epilepsy might be related to the site of epileptic focus and predisposition of patients as well.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509063 TI - [Effect of a muscarinic (M1) receptor agonist on sympathetic nerve activity in rats]. AB - The present study was undertaken to elucidate the effect of novel muscarinic (M1) receptor agonist, AF102B, (+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3') quinuclidine hydrochloride hemihydrate, on the sympatho-adrenomedullary function of anesthetized rats. Male Wistar rats were anesthetized intraperitoneally with urethane and alpha-chloralose. After immobilization with gallamine triethiodide, respiration was maintained artificially. Arterial blood pressure and heart rate were continuously monitored. Postganglionic inferior cardiac sympathetic nerve activity and preganglionic adrenal sympathetic nerve activity were recorded using an electrophysiological technique. In order to evaluate the adrenomedullary function, adrenal venous catecholamine secretion rate was also determined by HPLC ECD method. Intravenous administration of AF102B (1 mg/kg, 10 mg/kg) produced a dose-dependent increase in cardiac sympathetic nerve activity that was accompanied with tachycardia both in nerve intact and pithed rats. AF102B produced a pressor effect in pithed rats but not in nerve intact rats. The AF102B induced responses in pithed rats were significantly attenuated by the pretreatment with a M1 receptor selective antagonist, pirenzepine (50 micrograms/kg, i.v.). Moreover, AF102B produced a significant increase in adrenal epinephrine secretion rate without any increase in adrenal sympathetic nerve activity, which was also antagonized by pirenzepine pretreatment. These findings suggest that AF102B possesses an excitatory effect on the sympatho adrenomedullary function which is mediated via pirenzepine sensitive muscarinic receptor of M1 subtype in anesthetized rats. PMID- 8509064 TI - Type X collagen does not bind to matrix vesicles. AB - Cultured chick embryo tibial hypertrophic chondrocytes released matrix vesicles and Type X collagen into the culture medium. When the culture medium was filtered through a 0.1 micron nitrocellulose filter, both the matrix vesicles, measured as alkaline phosphatase, and the Type X collagen were retained quantitatively. None of the other collagen types in the culture medium was retained on the filter. Dissolution of the matrix vesicles on the filter in detergent solutions resulted in quantitative solubilization of the Type X collagen also. These results suggested that the Type X collagen was intimately associated with the matrix vesicles. However, when membrane filters that were composed of materials other than nitrocellulose, and that had a range of pore sizes, were used to filter the culture medium, the ratios of total matrix vesicles to total Type X collagen retained on the filters ranged from 53 (polysulfone membranes) to 0.3 (nitrocellulose-cellulose acetate membranes). Thus it is concluded that the quantitative retention of matrix vesicles and Type X collagen on 0.1 micron nitrocellulose filters was due to true filtration of the matrix vesicles and to selective adsorption of the Type X collagen. Removal of the noncollagenous extensions from the Type X collagen by brief pepsin or trypsin treatment converted the Type X collagen to its 45 kDa collagenous domain, which was no longer retained on nitrocellulose filters, suggesting that the adsorption of the Type X collagen on the filters was through one or both of its noncollagenous extensions. When the culture medium was subjected to ultracentrifugation to pellet the matrix vesicles, 98% of the membrane-associated alkaline phosphatase (matrix vesicles) was pelleted but only 15-20% of the Type X collagen was recovered in the pellet. These results indicate that matrix vesicles and Type X collagen are not the associated products of hypertrophic chondrocyte. PMID- 8509065 TI - [Studies on the responsiveness of alveolar T cells to proliferative stimuli and on surface antigens]. AB - Lymphocyte alveolitis which can be detected by bronchoalveolar lavage is a characteristic feature of pulmonary sarcoidosis and has been thought to be a latent or preceding pathogenetic process of granuloma formation in the lung. To explore the mechanism of this lymphocyte accumulation, the capacity of alveolar T cells obtained from patients with pulmonary sarcoidosis to release interleukin-2 (IL-2) was assessed and compared with that of autologous peripheral blood T cells. Contrary to previous reports, spontaneous production of IL-2 by unstimulated alveolar T cells was not observed. When stimulated with phytohemagglutinin (PHA), alveolar T cells released considerable amounts of IL-2, however, still less than blood T cells. We next measured intracytoplasmic free calcium ion concentrations ([Ca2+]i) which are intimately related to cell activation triggered by proliferative stimuli. Alveolar T cells in patients with pulmonary sarcoidosis showed lowered responses of [Ca2+]i than blood T cells when stimulated with PHA, thus, demonstrating PHA-hyporesponsiveness at the second messenger level. Meanwhile, [Ca2+]i response of alveolar T cells stimulated with anti-CD3 antibody was higher than that of blood T cells. To investigate mechanisms underlying this unique responsiveness of alveolar T cells, we first examined cell surface expression of alpha beta T cell receptor (TCR). Flow cytometric analysis showed reduced expression of TCR by alveolar T cells compared with blood T cells, a phenomenon commonly called modulation. Since modulation of TCR/CD3 molecular complex is reportedly associated with T cell hyporesponsiveness to lectins, modulation appeared to account, in part, for the reduced IL-2 release by PHA-stimulated alveolar T cells. On the other hand, the present study revealed that memory T cells were dominant among alveolar T cells. This fact also seemed to be responsible for contrasting responses of [Ca2+]i to PHA and anti-CD3 antibody mentioned above, since mitogenic response of memory T cells coincide well with [Ca2+]i response of alveolar T cells. Interestingly and importantly enough, both modulation and memory T cell-dominancy in alveolar T cells were also observed in normal subjects. Accordingly, these findings suggest that responsiveness of alveolar T cells to mitogenic stimuli observed for patients with sarcoidosis is a feature shared by alveolar T cells in health and disease. Thus, present study revealed characteristics of alveolar T cells in general taking advantage of investigation of IL-2 production by alveolar T cells in sarcoidosis. PMID- 8509066 TI - [Molecular analysis of transformation into blast crisis in chronic myelogenous leukemia]. AB - Molecular events associated with the transformation into blast crisis phase in Ph1-positive CML were analyzed in the present study. The 9;22 chromosomal translocation in CML generates the bcr/abl fused gene coding P210bcr/abl that has enhanced tyrosine kinase activity. In 55 CML cases, Southern and RT-PCR analysis revealed that breakpoints of the bcr gene on chromosome 22q11 were clustered in M bcr, except for one case and no obvious difference was observed between chronic and crisis phases. However, blast crisis cells displayed enhanced the expression of bcr/abl mRNA, when compared with those in chronic phase cells. By DNA transfection and PCR analysis, the point-mutational activation of N-ras oncogene was rarely identified, and no point-mutational activation of fms gene was found in the crisis phase cases. On the other hand, 2 out of 13 crisis cases contained gross alteration of p53 anti-oncogene. Furthermore, all 4 myeloid crisis cases and K562 cells showed disappearance of the P53 transcript, and MC3 cells derived from a myeloid crisis case showed an aberrant transcript, whereas chronic phase cases, Ph1-positive ALL cell lines and lymphoid crisis cases including NALM-1 cells showed normal expression of the P53 gene. At present, the precise mechanism associated with the blastic trans-formation in CML remain to be determined. The present study suggested one possibility that a selective and progressive process of Ph1 clone with high expression of the bcr/abl gene may be involved with the transformation into non-lymphoid crisis phases from chronic phases. In addition, this progression may be accelerated by the alteration of p53 anti-oncogene, or/and rarely by the point-mutational activation of ras oncogene family. PMID- 8509067 TI - [Selective thyroid angiography: techniques, diagnosis and indications]. AB - In the clinical research on angiographic diagnosis of thyroid tumor over twenty years, techniques, diagnostic points and limitations in angiogram were studied, and its indications and significance were reviewed. 1) As about 80% of the feeding artery for thyroid tumor was the superior thyroid artery, superior and inferior thyroid angiography via the femoral artery can be a basic method for angiographic diagnosis. 2) The success rate of insertion into superior and inferior thyroid artery depended on age, vascular anatomy, the shape of catheter, technique and procedure. The success rate was improved from 57.3% to 86.9% by reconsideration and devices. 3) The diagnostic points in thyroid angiographic findings are the morphological character of tumor vessel, the margin of tumor stain and the condition of its density. By checking these three points, the correct diagnostic rate of 94.7% was obtained in the differential diagnosis of malignant and benign. 4) Microangiogram and pathological findings of resected specimen were compared. The results suggest that the variety of width and distribution of vascular space in tumor and secondary degeneration prevent accurate diagnosis. 5) Today, noninvasive diagnostic methods for thyroid tumor have been advanced, therefore eight new indications of selective thyroid angiography for extraglandal change are proposed. PMID- 8509068 TI - [Regional differences in the pineal gland of the cotton rat, Sigmodon hispidus. Light and electron microscopic observations]. AB - The determination of volumes of the distal and proximal halves of the pineal glands of cotton rats (Sigmodon hispidus) and Sprague-Dawley rats revealed that the volume of the proximal half was far larger in cotton rats than in Sprague Dawley rats. Light and electron microscopic examination of the distal, middle and proximal pineal regions in the cotton rat revealed the presence of regional differences in parenchymal cells, capillary endothelial cells and pericapillary spaces. Nuclear sizes of pinealocytes were larger in the distal region than in the middle and proximal regions. The diameter of granulated vesicles and the contents in lysosome-like bodies in pinealocytes in the distal and middle regions were different from those in the proximal region. Interstitial cells and astrocytes surrounded pericapillary spaces; the former was localized in the peripheral area of the distal and middle regions, whereas the latter was found throughout the organ. Astrocytes were more abundant towards the proximal region. The capillary endothelium was often fenestrated in the distal region, whereas the fenestrae were few in the middle region and absent in the proximal region. Pericapillary spaces were large in the distal and middle regions, but narrow in the proximal region. Postganglionic sympathetic nerve fibers were distributed throughout the organ, whereas myelinated and unmyelinated nerve fibers, survived after superior cervical ganglionectomy, were found in the distal and middle regions, but not in the proximal region. Sympathetic and non-sympathetic nerve fibers lay adjacent to interstitial cells and astrocytes. These regional differences may reflect functional differences in various pineal regions of the cotton rat. PMID- 8509069 TI - Taking a new approach to independent living. PMID- 8509070 TI - Intensive case management of persons with chronic mental illness who abuse substances. PMID- 8509072 TI - Occupational therapy intervention with children in school systems. PMID- 8509071 TI - Clinical management of lithium-induced polyuria. PMID- 8509073 TI - MacArthur data reanalyses: examples from the second stage of empirical review. PMID- 8509074 TI - Housing and supports for persons with mental illness: emerging approaches to research and practice. AB - OBJECTIVE: An approach referred to as "supported housing," based on principles of consumer choice, integrated community housing, and flexible services, is replacing residential treatment facilities for persons with psychiatric disabilities. To improve understanding of the new approach, its evolution, and issues involved in its implementation, this paper reviews studies of the effectiveness of traditional housing programs and early reports of the development of supported housing programs. METHODS: A data base of more than 4,000 journal articles and book chapters published over the past 15 years was searched; both research studies and policy analyses were included. RESULTS AND CONCLUSIONS: Because of national and state policy shifts toward supported housing and growing evidence that both consumers and their families favor this new approach, supported housing models appear to be increasingly replicated throughout the U.S. Innovative financing strategies, such as forming coalitions to develop housing or creating capital funds, have been implemented. Results from studies of established programs indicate that support services for consumers should include working with individuals to formulate their housing and support goals; financial assistance in acquiring long-term stable housing; help in searching for an apartment and moving; assistance in managing money and participating in leisure activities; assistance with medication; ongoing monitoring of needs; crisis support; and peer support. Future research should focus on promoting consumers' choices and organizing flexible services to help them succeed in the community. PMID- 8509075 TI - An overview of surveys of mental health consumers' preferences for housing and support services. AB - OBJECTIVE: The author examined the methodology and results of studies that surveyed mentally ill clients' preferences related to housing and support services to gain an overview of demographic characteristics, current and preferred housing situations, and preferred types of staff supports and social and material supports in a nationally representative sample of clients. METHODS: Through mailings to state departments of mental health and local mental health providers and advocates, a national survey of residential providers, and other contacts with mental health agencies, the author identified a total of 43 studies of mental health consumers' preferences for housing and supports conducted between 1986 and 1992. The results of 26 of the studies whose methodologies permitted comparison of findings were summarized. RESULTS: Consumers consistently reported that they would prefer to live in their own house or apartment, to live alone or with a spouse or romantic partner, and not to live with other mental health consumers. Consumers reported a strong preference for outreach staff support that is available on call; few respondents wanted to live with staff. Consumers also emphasized the importance of material supports such as money, rent subsidies, telephones, and transportation for successful community living. CONCLUSIONS: To accommodate consumers' preferences, mental health systems should work toward providing flexible supports corresponding to the episodic nature of psychiatric disability and should expand their advocacy for affordable housing and for increased income for people who depend on disability benefits and other entitlements. PMID- 8509076 TI - Implementing supported housing in state and local mental health systems. AB - The Ohio Department of Mental Health has aggressively promoted the development of supported housing--affordable, permanent community housing along with a system of needed support services--for adults with serious mental illness. The authors outline the development of supported housing programs by the state and by Franklin County, Ohio, beginning in the mid-1980s. The county's program, implemented mainly through the county authority for substance abuse and mental health services and a separate nonprofit housing corporation, was assisted by a major grant and loan from the Robert Wood Johnson Foundation Program on Chronic Mental Illness, federal Section 8 housing certificates, and special grants from the Ohio Department of Mental Health. Both the state and the county formulated and followed comprehensive housing development plans. Both entities used creative financing mechanisms, including leveraging, to bring in additional public and private funds, and they worked to involve consumers and families in formulating policies and developing services. PMID- 8509077 TI - The psychiatrist's role in supported housing. AB - The role of a psychiatrist in relation to supported housing programs for persons with serious psychiatric disability has not been well defined. The psychiatrist clearly has an important role in prescribing medication in a way that supports the client's own goals and in helping arrange for medical care or hospitalization when needed. The psychiatrist's influence can help the community and the client accept supported housing, and the psychiatrist has broad expertise ranging from crisis intervention to transference issues that can be useful to clients and staff. At the same time, some professionals and advocates are concerned that a psychiatrist's involvement can interfere with the rehabilitative orientation of supported housing or impose an undue degree of paternalism. Psychiatrists who understand the fundamental values of supported housing and who can tolerate some role ambiguity can greatly assist their clients to live more independent lives in the community. PMID- 8509078 TI - Continuity of care and approaches to case management for long-term mentally ill patients. AB - Consensus does not yet exist about the definition of case management as it is practiced in the care of long-term mentally ill patients. Case management interventions may be arrayed on a continuum, with brokering and clinical approaches at the poles. However, most actual case management programs fall along the continuum and not at the extreme poles. The functions of case management in the care of long-term patients correspond closely to nine principles of continuity of care that transcend specific case management styles. The nine principles are an administrative climate supportive of long-term patients, ready access by patients to the services they need, provision of a full array of services, individually tailored treatments, flexible program offerings, linkage among agencies serving the patient, a continuing relationship between patient and caregiver, patient involvement in service planning, and recognition of cultural factors affecting treatment. The author discusses how the concept of continuity of care can be used in considering policy issues such as staffing of case management services and suggests that service systems may find it advantageous to offer several different case management approaches to accommodate patients' individual needs. PMID- 8509079 TI - A framework for evaluating the economic impact of case management. AB - Confusion about the cost-effectiveness of case management stems partly from poorly defined assumptions about outcomes and unclear theories of how case management affects costs. The authors discuss how cost-effectiveness is influenced by the characteristics of various case management models, characteristics of the clients served, and contextual factors, including resources available in the treatment system and financial incentives built into various payment mechanisms. Important differences exist between case management models in the mechanisms favored for managing resources, including whether the client or the case manager is primarily responsible for directing the course of treatment, whether reduction in hospitalizations is a primary goal, whether team case management is used, and how the size of caseloads is determined. PMID- 8509080 TI - Using awareness of religious factors to enhance interventions in consultation liaison psychiatry. AB - Religion plays an important role in the lives of most Americans and often influences the ways patients react to medical illness. However, the religious aspects of patients' lives are often ignored or only superficially explored by consultation-liaison psychiatrists. Building on an existing typology, the authors use six dimensions of religious experience to discuss approaches to incorporating religious factors in the psychiatric evaluation and treatment of the hospitalized medical patient; the dimensions include religious beliefs, participation in religious rituals, and affiliation with a religious community. Case examples illustrate how these approaches can enhance the work of the consultation-liaison psychiatrist and improve the patient's coping ability. PMID- 8509081 TI - Projections of inpatient admissions to specialty mental health organizations: 1990 to 2010. AB - OBJECTIVE: To help predict changes in patterns of service delivery, the total number of inpatient admissions to specialty mental health organizations and the number of elderly persons (over age 65) admitted were projected in five-year intervals between 1990 and 2010. METHODS: One set of projections is based on 1986 rates of use and their coefficients of variation. A second, more accurate, set is based on 1990 rates derived from logarithmic projections of trends from 1980 to 1986 and the coefficients of variation for the 1986 rates. RESULTS: Projections based on 1990 rates show an increase of more than 25 percent in the total number of inpatient admissions to all specialty mental health organizations between 1986 and 2010 and an increase of more than 40 percent in elderly admissions. Nonfederal general hospitals are expected to have the largest increases in the number of total admissions, and state and county mental hospitals the smallest. The greatest percentage growth in total admissions will occur in private psychiatric hospitals. For elderly persons, inpatient admissions to Veterans Affairs medical centers will show the largest percentage increase, and admissions to state and county mental hospitals the smallest. By 2010 the majority of elderly admissions (67.6 percent) will be to nonfederal general hospitals. CONCLUSIONS: Plans to cope with increased demand for inpatient services should take into account the potential economic consequences of the forecasted changes as well as their effects on allocation of and access to services. PMID- 8509082 TI - State policies and programs that address the needs of mentally ill mothers in the public sector. AB - OBJECTIVE: The authors sought to determine whether state departments of mental health have specific policies and programs addressing the needs of mentally ill women served in the public sector who have preschool-age children. METHODS: A questionnaire was sent to the commissioner of mental health for each state and the District of Columbia. Questions addressed whether information was routinely collected on the parenting status of women who receive public-sector psychiatric services, whether services targeting mentally ill women with young children were available, and whether the state had policies concerning hospitalized women who are pregnant or who have young children. RESULTS: Sixteen states routinely collect data on whether women who receive public-sector services have young children. Four states have residential programs for mentally ill women and their children. About half of the states have programs for assessing parenting skills and outpatient services focused on improving those skills. No state has a policy about visitation between a hospitalized mentally ill mother and her children. Twenty states have policies for the care of hospitalized pregnant patients, primarily for their medical management. CONCLUSIONS: Further efforts are needed to identify mentally ill women in the public sector who have young children, to enhance the parenting skills of mentally ill patients, and to promote positive outcomes for their children. PMID- 8509083 TI - Benefits and challenges of using consumer staff in supported housing services. PMID- 8509084 TI - Housing preferences of homeless men and women in a shelter population. PMID- 8509085 TI - A national study of housing affordability for recipients of supplemental security income. PMID- 8509086 TI - Work and quality of life. PMID- 8509087 TI - Amok as a disorder. PMID- 8509088 TI - The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. AB - OBJECTIVE: To study the localisation of treponemes and to analyse the inflammatory infiltrate in biopsy specimens from patients with primary or secondary syphilis, or early infectious yaws. MATERIALS AND METHODS: Skin biopsies originating from human lesions of primary (29x) or secondary (15x) syphilis (Rotterdam), or early yaws (18x) (West Sumatra) were studied. Different histochemical and immunohistochemical detection methods were used in this study. RESULTS AND CONCLUSION: The histochemical silver staining method according to Steiner revealed the presence of T. pallidum in all cases of primary syphilis studied. In 10 out of 14 cases of secondary syphilis, treponemes were demonstrated. With an immunofluorescence staining technique (IF) using anti-T. pallidum antiserum raised in rabbits (a-Tp), T. pallidum was demonstrated in 28 out of 29 cases of primary syphilis, and in 14 out of 14 studied cases of secondary syphilis. The silver staining method and IF showed identical localisations of T. pallidum (mainly in the dermal-epidermal junction zone or throughout the dermis). Using a-Tp antiserum in the indirect immunofluorescence technique, T. pertenue could be demonstrated in the dermis more often than with Steiner silver staining. However, epidermotropism of T. pertenue in yaws specimens was remarkable, compared with more mesodermotropism of T. pallidum; numbers of T. pertenue in the dermis were limited in all specimens. The dermal inflammatory infiltrate in primary and secondary syphilis was composed mainly of lymphocytes and plasma cells. In most cases more T (CD3 positive) cells than B (CD22 positive) cells were present. Regarding T cell subpopulations, in primary syphilis, T helper/inducer (CD4 positive) cells predominated in 86% of cases. In secondary syphilitic lesions, numbers of T helper/inducer cells were less frequent than or equal to T-suppressor/cytotoxic (CD8 positive) cells in 60% of cases. Remarkably, in yaws specimens the inflammatory infiltrate consisted mainly of IgG, but also IgA and IgM producing plasma cells. T or B lymphocytes were scarce, which is in sharp contrast with findings in syphilitic lesions. PMID- 8509089 TI - Clinico-epidemiological study of donovanosis in Durban, South Africa. AB - OBJECTIVE: To describe the epidemiological and clinical features of donovanosis and their relevance to the possible coincident risk of HIV-1 transmission in patients attending an STD clinic. DESIGN: Assessment of patients with donovanosis diagnosed by the detection of Donovan bodies on tissue smears stained by the RapiDiff technique. SETTING: City Health STD Clinic, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: One hundred and seventy one patients with donovanosis. RESULTS: Donovan bodies were detected in 171 (130 men, 41 women). Ulcers were present for longer than 28 days in 72 (55.4%) men and 19 (46.3%) women. Ninety five (55.6%) came from rural areas. Lesions were ulcero granulomatous in 162, hypertrophic in eight and necrotic in one. Anal lesions were detected in one woman. Only one of 21 regular sexual partners examined was infected with donovanosis. Complete healing was observed in 41 (24%) who attended for follow up. Extensive lesions were sometimes observed in pregnant women. Serological tests for syphilis were positive in 40 (23.4%). HIV-1 antibodies were detected in 4/48 men and 0/15 women who underwent HIV testing. Donovanosis ulcers in three HIV-1 seropositive men were cured by standard antibiotic therapy. CONCLUSIONS: Delay in presentation, extensive areas of genital ulceration and lack of co-existent infection with donovanosis among sexual partners were notable features. Primary health care facilities in rural areas do not appear to be providing an adequate service for patients with donovanosis. HIV control programmes should consider specific measures aimed at eradicating donovanosis in areas where the condition is prevalent. PMID- 8509090 TI - Management of genital herpes by genitourinary physicians: does experience or doctor's gender influence clinical management? AB - OBJECTIVE: To determine the variation in management of genital herpes by genitourinary physicians, and whether their duration of experience or gender influence their clinical management. METHODS: A postal questionnaire was sent to UK consultant genitourinary physicians with detailed questions about management of primary and recurrent herpes. The gender and duration of genitourinary medicine experience of the physicians were also recorded. RESULTS: One hundred and eighty two questionnaires were sent, 112 (62%) returned. Eighty-one (72%) physicians treat all patients with primary genital herpes, but physicians with more than 20 years experience were significantly (p < 0.05) more likely to treat only "severe" primary attacks. Most experienced physicians were also most likely (p < 0.05) to prescribe topical acyclovir. Prescription of suppressive acyclovir was also influenced by the experience of the physician, the least experienced physicians being more likely to prescribe to patients who were HIV antibody positive or to those entering new relationships, whereas the more experienced prescribed to those patients who were particularly anxious (p < 0.05 for each of these). Male physicians were significantly more likely to agree with the proposition that men cope better with genital herpes (54%) than female physicians (24%, p < 0.01). CONCLUSION: The response to the questionnaire illustrates that management of genital herpes is influenced by the duration of the physicians clinical experience. Gender of the physician may have an indirect role to play as we have shown that physicians differ in their perception of how the sexes cope with genital herpes. PMID- 8509091 TI - Comparison of an enzyme immuno assay (Antigenz Chlamydia) with cell culture for the detection of genital chlamydial infection in high and low risk populations. AB - OBJECTIVE: To evaluate a new enzyme immuno assay, Antigenz Chlamydia, for the detection of chlamydial antigen in urogenital samples using cell culture as the gold standard for comparison and direct immuno fluorescence to aid resolving the discrepancies. SUBJECTS: 212 men and 303 women attending an STD clinic and 404 women of child bearing age attending gynaecological clinics. RESULTS: Sensitivity, specificity, predictive value of positive result and predictive value of negative result of the new test were 77.6%, 99.0%, 94.3%, and 95.7% respectively in the high risk population with a prevalence of 16.5%. In the low risk population the figures were 84.2%, 94.5%, 43.2% and 99.2% respectively with a prevalence of 4.7%. CONCLUSION: Antigenz Chlamydia is an easy and quick test to perform. The test is suitable for use in high risk and low risk populations provided all positive samples are confirmed. PMID- 8509092 TI - Determinants of cervical Chlamydia trachomatis infection in Italy. The Italian MEGIC Group. AB - OBJECTIVE: to analyse the prevalence of cervical chlamydia infection and its determinants in an Italian population of women attending outpatients services for contraceptive counselling or routine gynaecological examination. METHODS: between November 1989 and November 1990 we conducted a cross-sectional study on the prevalence of cervical Chlamydia trachomatis infection among women attending the outpatients service of seven university clinics in Northern (three centres), Central (three centres) and Southern (one centre) Italy. Eligible for the study were subjects with symptomatic low gynaecological tract infection (a total of 2071 women), a history of recurrent abortions (two or more miscarriages and no livebirth (416 subjects)), or sterility (371 subjects), plus a sample of asymptomatic women observed for contraceptive counselling or routine gynaecological examination identified on randomly selected days at the participating centres (1321 subjects). During the gynaecological consultation women were asked about their general characteristics, reproductive history, contraceptive and sexual habits, and history of sexually transmitted diseases (STD) using a standard questionnaire. An endocervical specimen was obtained with a plastic swab. The direct smear immunofluorescent antibody test (IFA test) was used to detect chlamydia antigens. RESULTS: out of the 2071 women with genital infection, 104 (5.0%) had cervical chlamydia infection; the corresponding percentages were 4.6 (19/416), 5.4 (20/371) and 3.9 (51/1321) respectively in women with recurrent abortions, sterility and in asymptomatic subjects. The risk of chlamydia infection was higher in women reporting a history of STD: in comparison with those without a history of STD, the relative risk of chlamydia infection was 1.4 (95% confidence interval, CI, 1.0-2.0). Among women reporting current use of a contraceptive method the risk of cervical chlamydia infection was lower in current users of barrier methods; in comparison with oral contraceptive users, the RR was 0.4 (95% CI, 0.2-0.8) in barrier methods users and 0.5 (95% CI, 0.2-1.1) in intrauterine device or other methods users. No consistent relationship emerged with age, reproductive history or number of sexual partners over the last 12 months. CONCLUSION: in this Italian population the frequency of cervical chlamydia infection appeared to be lower than in other selected groups from Northern European and American countries. Users of barrier contraception methods were at reduced risk of infection. PMID- 8509093 TI - The management of patients with inflammatory smear results in general practice. AB - OBJECT: To ascertain the management of inflammatory smear results by general practitioners. DESIGN: Postal questionnaire survey. SUBJECTS: All 200 general practitioners on Wirral Family Health Services Authority list as principals in 1990 and 1991. MAIN OUTCOME MEASURES: Answers to questions covering a variety of aspects concerning the management of inflammatory smear results in general practice. RESULTS: One hundred and thirteen (57%) replied. Ninety per cent have facilities to test for Trichomonas vaginalis and Candida albicans. Sixty eight per cent were able to test for Chlamydia trachomatis. A high vaginal swab (HVS) was the commonest swab taken (88%); 31% of doctors included a swab for Chlamydia trachomatis. Of doctors who gave treatment without microbiological confirmation 74% gave metronidazole and 64% gave tetracycline or erythromycin. Eighty five per cent repeat smears are undertaken within three months. Ninety seven per cent of doctors said more detailed information would be helpful on the cytology report. One hundred per cent of doctors referred to a gynaecologist of colposcopy was advised. Male sexual partners were advised to attend the Department of Genitourinary Medicine by 12% of doctors (70% do not refer to either their general practitioner or genitourinary department). CONCLUSION: Most patients with inflammatory smear results are managed by their general practitioner without reference to specialist services. Many patients are not investigated for infection but treatment often includes medication which covers the most likely or potentially serious genital pathogens. More detailed advice given with the cytology report on further management or a local protocol would be helpful to aid management in this difficult area. If recommendations for referral of certain groups of patients to genitourinary departments were implemented the present workload of the department would be increased. PMID- 8509094 TI - Systemic Pneumocystis carinii pneumonia prophylaxis with dapsone and pyrimethamine fails to protect against extrapulmonary pneumocystosis. AB - Extrapulmonary pneumocystosis is a feature of severe immunosuppression which earlier reports have suggested is limited to patients receiving either no prophylaxis or aerosolised pentamidine. We report a case of disseminated pneumocystosis which developed in an HIV positive homosexual man despite systemic primary Pneumocystis carinii pneumonia prophylaxis. PMID- 8509095 TI - Adolescents, sexual behaviour and implications for an epidemic of HIV/AIDS among the young. AB - OBJECTIVE: To determine the patterns of sexual behaviour, condom use and sexually transmitted diseases among young New Zealanders, and the characteristics of those with many sexual partners. SUBJECTS: A cohort of young people enrolled in a longitudinal cohort study, and followed up since age three. METHODS: Subjects were interviewed at age 18 years as part of a multidisciplinary health and development study. Questions about sexual behaviour were presented by computer. RESULTS: Overall 862/1027 (83.9%) surviving in the cohort was interviewed. Only 1.4% declined to answer the section on sexual behaviour. Sexual intercourse in the previous 12 months was reported by 57.6% of the young men and 67.9% of the young women. Amongst those who were sexually active more of the young men reported multiple partners than the young women (59.8% v 46.5% p < 0.001). There was a trend for increasing number of partners with indices of lower school achievement but no significant association with socio-economic status. Condom use decreased with increasing number of partners for the young women, and for the young men there was no association. Sexually transmitted diseases were reported more commonly with increasing number of sexual partners for both men and women. The rates of sexual activity were substantially higher than reported in a comparable survey 20 years ago. CONCLUSIONS: The pattern of sexual behaviour and condom use, and the occurrence of sexually transmitted diseases in this sample give cause for concern about the spread of sexually transmitted diseases including the possibility of an epidemic of HIV among heterosexual young people in New Zealand. The findings should help in targeting health promotional activities within this age group. PMID- 8509096 TI - Sexually transmitted diseases in children: adolescents. PMID- 8509097 TI - A history of sexually transmitted diseases in Thailand: policy and politics. AB - This paper provides a brief history of sexually transmitted diseases (STDs) in Thailand. The presentation is divided into three main sections: the period up to the 1930s; the period from the 1930s until the end of the early 1980s; and the period from the early 1980s until the present, the so-called 'AIDS Era'. The discussion in each of these sections focuses, as far as sources permit, on the epidemiological picture, as well as describing public and official responses to these diseases. In the final part of the paper consideration is given to these findings in relation to the present situation in Thailand regarding the HIV/AIDS epidemic. PMID- 8509098 TI - The importance of ethnicity as a risk factor for STDs and sexual behaviour. PMID- 8509099 TI - Recurrence of condylomata acuminata following cryotherapy is not prevented by systemically administered interferon. AB - OBJECTIVE: To determine whether interferon alpha-2a, when utilised as adjuvant chemotherapy following ablation of condylomata acuminata (genital warts) by cryotherapy, is effective in the prevention of recurrences. DESIGN: Randomised, placebo-controlled, double-blind study. Statistical analysis was by 2-tailed Fisher's Exact Test. PATIENTS: 97 patients with recurrent condylomata acuminata. INTERVENTION: 49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a, and 48 received cryotherapy plus placebo. Of these, 36 and 37 patients, respectively, completed the study and were evaluable. MAIN OUTCOME MEASURE: Clinical eradication of condylomata for six months following adjuvant chemotherapy. RESULTS: By completion of the adjuvant chemotherapy, 10 (28%) interferon recipients and 16 (43%) placebo recipients experienced recurrences. At six months follow-up, 25 (69%) interferon and 27 (73%) placebo recipients experienced recurrences. In the six months following interferon therapy, only 31% of interferon and 27% of placebo recipients remained free of recurrences (p = 0.99). CONCLUSIONS: Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeutic adjuvant to cryotherapy when used alone in the therapy of genital warts in this population of patients with recurrent condylomata. PMID- 8509100 TI - Partner notification for HIV infection in the United Kingdom: a look back on seven years experience in Newcastle upon Tyne. AB - OBJECTIVE: To examine the outcome of partner notification for HIV infection. DESIGN: Retrospective analysis of medical, health adviser and counsellor records. SETTING: Teaching hospital, Newcastle upon Tyne. PATIENTS: All newly diagnosed cases of human immunodeficiency virus (HIV) infection and their sexual partners. MAIN OUTCOME MEASURES: Attendance of contact at genitourinary medicine clinics for counselling and testing. Seropositivity rate of people attending as a result of partner notification. RESULTS: Of the 80 partners attending as a result of partner notification 79 were tested. Twenty-five of these (31.6%) were seropositive. This was 21.9% of our newly diagnosed caseload. Seventy-five attended following patient referral and five as a result of provider referral. Discrepancies between districts in policies of provider referral prevented two partners being notified. CONCLUSIONS: Partner notification is an effective method of ensuring that people with a very high risk of HIV infection have access to counselling and medical care. Complete integration of notification services throughout the UK is required. PMID- 8509101 TI - The association of gonorrhoea and syphilis with premature birth and low birthweight. AB - OBJECTIVE: Provide evidence from prospective data that Neisseria gonorrhoeae may be an important cause of premature delivery and low birth weight in areas with high prevalence of genital infections. SETTING: Department of Obstetrics and Gynaecology, Kalafong University Hospital, Pretoria, South Africa in collaboration with the Departments of Microbiology and of Gynaecology and Obstetrics, Katholieke Universiteit, Leuven, Belgium. SUBJECTS: Two hundred and fifty six consecutive black pregnant women were examined during the first antenatal visit, and one to four weeks later a second culture for N gonorrhoeae was taken at random in 67 of them. Hundred and sixty seven were analysable, 75 were lost to follow up. METHODS: After obtaining detailed clinical history, an endocervical specimen for N gonorrhoeae culture (Thayer-Martin) and C trachomatis antigen detection (Chlamydiazyme (R)) was taken. Syphilis was diagnosed when both reactive plasma protein (RPR) and T pallidum haemagglutination inhibition assay (TPHA) were positive. Prematurity was defined as delivery at less than 37 gestational weeks. RESULTS: Infection with N gonorrhoeae (n = 9) and untreated syphilis (n = 7) were both associated with prematurity and low birth weight. After multi-variate regression analysis, age-adjusted parity, late sexual debut, number of recent sexual partners, infection with N gonorrhoeae and infection with syphilis revealed significant associations with low birth weight. However, infection with C trachomatis, presence of abundant vaginal discharge, social class, Trichomonas vaginalis infection, gestational weeks at first antenatal visit and number of previous miscarriages did not reveal such an association. Attributable risk of untreated gonorrhoea for premature birth was 72% and routine cultures were cost-benefit efficient. CONCLUSIONS: At least in countries where the prevalence is high, genital infections as well as the risk factors for acquiring them (young age, late sexual debut, number of recent partners) play a major role in the aetiogenesis of prematurity and low birth weight. N. gonorrhoeae is a main contributor, and in high prevalence areas it should be routinely looked for and treated for during pregnancy. PMID- 8509102 TI - Further studies of psychophysically determined maximum acceptable weights and forces. AB - The effects of lifting boxes without handles, pulling long distances, carrying different size boxes, combining three handling tasks, and lifting with extended horizontal reach were studied using a psychophysical methodology. Six male industrial workers performed 42 variations of lifting, lowering, pushing, pulling, and carrying tasks. Lifting boxes without handles produced consistent decreases (median, 16%) in maximum acceptable weights when compared with lifting boxes with handles. Lifting with extended horizontal reach (approximately 48 cm) produced consistent decreases (median, 48%) in maximum acceptable weights when compared with lifting close to the body (approximately 17 cm). No significant heart rate or oxygen consumption differences occurred in either of these variables. No significant differences in maximum acceptable weight of carry were observed among box sizes; however, the maximum acceptable force of pulling was lower for longer (15.2 m) pulling tasks. The maximum acceptable weight for combination tasks was similar to that of the limiting component. PMID- 8509103 TI - The visibility of symbolic highway signs can be increased among drivers of all ages. AB - Visibility and comprehension of standard text, standard symbolic, and improved symbolic highway signs were compared among young, middle-aged, and elderly observers. The average distance at which standard symbolic signs could be identified was about two times that of text signs for all three age groups. The visibility distances of the improved symbolic signs, which were designed using an optical blur (i.e., low-pass) approach in order to avoid higher spatial frequencies, exceeded those of both text and standard symbolic signs. Visibility distance was decreased significantly among older drivers on some signs but not others. There were no significant age differences in the comprehension of symbolic signs. Acuity, a good predictor of visibility distance of both text and standard symbolic signs, was only weakly related to the visibility distance of the improved symbolic signs. These findings demonstrate that low-pass symbolic signs have significant advantages in visibility over their test counterparts for all drivers. PMID- 8509104 TI - Cognitive predictors of vigilance. AB - Three studies are reported of individual differences in performance of high event rate vigilance tasks. In each study, measures of attentional resource availability and elementary cognitive components of sustained attention were correlated with vigilance performance. It was predicted that correlates of vigilance should vary with two parameters of the task: the type of target discrimination required (simultaneous or successive) and the type of stimuli used (sensory or symbolic). Speed and accuracy of controlled, resource-demanding visual search predicted overall perceptual sensitivity on three out of four successive tasks used, but only one out of four simultaneous tasks, partially confirming the hypothesis that successive tasks are more strongly resource limited than simultaneous tasks. Other correlates of overall level vigilance did not appear to vary systematically with task parameters. Few correlates of temporal decrement in perceptual sensitivity were found, possibly for statistical reasons. The data suggest that measures of controlled search may be useful in predicting vigilance on certain real-world tasks, although a substantial part of the variance of vigilance tasks may not be predictable from short cognitive tasks. PMID- 8509105 TI - Performance under dichoptic versus binocular viewing conditions: effects of attention and task requirements. AB - Three experiments investigated subjects' ability to allocate attention and cope with task requirements under dichoptic versus binocular viewing conditions. Experiments 1 and 2 employed a target detection task in compound and noncompound stimuli, and Experiment 3 employed a relative-proximity judgment task. The tasks were performed in a focused attention condition in which subjects had to attend to the stimulus presented to one eye or field (under dichoptic and binocular viewing conditions, respectively) while ignoring the stimulus presented to the other eye or field, and in a divided attention condition in which subjects had to attend the stimuli presented to both eyes or fields. Subjects' performance was affected by the interaction of attention conditions with task requirements, but it was generally the same under dichoptic and binocular viewing conditions. The more dependent the task was on finer discrimination, the more performance was impaired by divided attention. These results suggest that at least with discrete tasks and relatively short exposure durations, performance when each eye is presented with a separate stimulus is the same as when the entire field of stimulation is viewed by both eyes. PMID- 8509106 TI - Effects of age and task similarity on dual-task performance. AB - When a dual tracking task consisting of two incoherent (uncorrelated) subtasks is partly integrated, such that it is characterized by incompatibility of similarity, or when axis similarity of subtasks is high, it may be difficult to map subtask stimuli to the proper responses. Especially for older adults, an increase in mapping demands may be a source of confusion (cross talk). In the present experiment this issue was addressed with a dual task consisting of two unrelated one-dimensional compensatory tracking tasks with position dynamics. Task performance was measured in terms of root mean square tracking error and cross-axial correlations. Tracking error data were consistent with the hypothesis that older subjects are penalized when there is incompatibility between control and display integration. In general, negative effects of incompatibility of integrality were the greatest when partial integration involved integration of the response component. Both performance measures indicated that with increasing incoherent similarity, task performance of the old subjects was more hampered than was that of their young counterparts. PMID- 8509107 TI - Getting nurses in the news. PMID- 8509108 TI - Katherine Claire Zimmer. Interview by Amanda Niskar. PMID- 8509109 TI - How to handle the stress of being a student. PMID- 8509110 TI - How to get the most out of career days. PMID- 8509111 TI - Nurse-midwifery. PMID- 8509112 TI - Charting a path for nursing. PMID- 8509113 TI - Learning to care for yourself as well as your patients. PMID- 8509114 TI - Developing a reciprocal program between student nurse organizations and hospitals. AB - Student nurse organizations can develop reciprocal programs with hospitals which can be mutually beneficial to both organizations. Hospitals need to recruit and retain qualified nurses through cost-effective methods. NSAs need to develop financial support for their group's activities. Both the hospital and the NSA need to expose students to various nursing roles in an effort to reduce reality shock. Developing a reciprocal relationship between an NSA and a hospital is one method of meeting the complementary objectives of both organizations. PMID- 8509115 TI - When the nursing student faces discouragement. PMID- 8509116 TI - Nursing: the joy and the challenge. PMID- 8509117 TI - The abuse of shifting shifts. AB - In summary, the evidence cited in this article argues convincingly for the conclusion that if some time scheduling actually endangers the health and well being of two of the vital human ingredients for the existence of a hospital, its nurses and its patients, then these practices are abusive. Furthermore, if nurses are deemed capable of fulfilling the varied and complex duties that sustain the lives of others, surely they are capable of taking responsible action to prevent or alleviate the conditions that put their own health and well-being at stake. But this is not possible without education that informs and the motivation to act. One level at which education and motivation are both at their best is in the new nursing graduate. Schools of nursing have the responsibility of giving graduates the best chance possible for safe, competent, and successful practice. Practicing nurses have a responsibility too. Besides being the best role models possible, we have the responsibility to give new graduates the best legacy possible. PMID- 8509118 TI - Health promotion and the elderly. PMID- 8509119 TI - The sanctity of life--and death. PMID- 8509120 TI - Conformational structure variations in DNA: a PCILO study. AB - Perturbative configuration interaction using localized orbital (PCILO) computations have been carried out on conformational preference of d(GpC) and d(CpG) units of Z-II DNA. By keeping the sugar pucker fixed in the crystallographic conformation, PCILO energies have been calculated as a function of torsion angles alpha and zeta around two P-O ester bonds with preselected values of beta, gamma and epsilon. The results indicate that the d(GpC) unit is energetically more stable than the d(CpG) unit and prefers a g+ t conformation in (alpha-zeta) hyper-space observed in the crystal structure. The d(CpG) unit, on the other hand, shows intrinsic preference for g-g- conformation with other torsion angles close to DNA-B structure. The possibility of d(GpC) unit responsible for the stability of Z-helix has been discussed. PMID- 8509121 TI - Effect of water stress on primary photosynthetic process: interaction with light and temperature. AB - Effect of water stress alone and in combination with light and temperature on chlorophyll fluorescence and photosynthetic electron transport have been studied in drought-resistant wheat. It was observed that water stress alone-did not modify the amplitude of variable fluorescence in leaf but showed slight decrease in photosynthetic electron transport. However, interaction with light caused significant decrease in the efficiency of photosynthesis. This was greater when photoinhibited at 30 degrees C than at 10 degrees C. Results suggest that water stress alone does not lead to significant damage to the primary photochemistry but photoinhibition causes both inhibition of electron transport activity and chlorophyll fluorescence. The damage was further enhanced by the combination of water stress and high temperature. PMID- 8509122 TI - Structural stability of beta-globulin, the low molecular weight protein fraction from sesame seed (Sesamum indicum L.) in alkaline solution. AB - Beta-globulin, a single polypeptide chain of molecular weight 15,000 +/- 1,000, undergoes denaturation in alkaline pH (7.0-13.0), thereby affecting the hydrodynamic properties of the protein, viz. a decrease in sedimentation coefficient from a value of 2.0s to 1.4s at pH 11.3, an increase in reduced viscosity from 0.042 dl/g to 0.158 dl/g at pH 12.6 and a decrease in partial specific volume resulting in a volume change of 6.3 +/- 1.0 ml/mole residue at pH 11.7. The perturbation of tryptophanyl residues and ionization of tyrosyl residues are preceded by alteration in conformational status of the protein. The fluorescence emission measurements indicate initial unfolding of the protein molecule which exposes the tryptophan and tyrosyl residues to the solvent. The tyrosyl phenolic group ionization is anomalous having a pKint value of 11.2. The reduced viscosity value reaches a plateau region at pH 12.5. PMID- 8509123 TI - The phenyl propanoid pathway enzymes in Solanum tuberosum exist as a multienzyme complex. AB - The elution profile of the core sequence enzymes of the phenyl propanoid pathway, namely phenyl alanine ammonia lyase, t-cinnamic acid 4-hydroxylase and p-coumaryl CoA ligase, on AcA 34 column suggested the existence of a high molecular form (P1) and a low molecular form (P2) for all the three enzymes. All the P1 forms eluted together in same fractions, while the P2 forms eluted out according to their respective molecular mass. Rechromatography of P1 form under identical conditions showed a similar elution profile (Q1 and Q2 forms). Further, the Q1 form did not show any significant increase in specific activity when compared to the P1 form. These results suggested the possibility of these enzymes existing as a protein cluster. Further confirmation was obtained on repeated column chromatography of the Q1 form in presence of 0.1 M KCl which did not result in complete dissociation of the complex to its individual enzyme components. The identification of the subunit polypeptide of the individual enzyme components in the multi enzyme complex and the in vitro demonstration of the phenyl propanoid core pathway reaction sequence using phenylalanine alone as a substrate supplementing the required cofactors for appropriate reactions substantiated that at least the core enzymes of the phenyl propanoid sequence existed as a multi enzyme complex. PMID- 8509124 TI - Purification and characterization of an alkaline proteinase from kidney cortex lysosomes. AB - An alkaline proteinase was purified to apparent homogeneity from buffalo (Bubalus bubalis) kidney cortex lysosomes by affinity chromatography on STI sepharose 4B and gel filtration over Sephadex G-100. The molecular weight of the enzyme was 17,000 and 21,000 by gel filtration and SDS/PAGE respectively. The purified enzyme was optimally active at pH 8.5-9.0 at 50 degrees C and hydrolysed synthetic substrates of chymotrypsin but not those of elastase or trypsin. It was inhibited by serine proteinase inhibitors like soybean trypsin inhibitor, limabean trypsin inhibitor and phenylmethyl sulphonyl fluoride. Immunologically, the enzyme was similar to chymotrypsin. The amino acid composition showed high content of acidic amino acids. This protein was detected in kidney, liver, spleen, pancreas and heart. PMID- 8509125 TI - Inhibition of mitochondrial oxidative phosphorylation and its electron transport pathway by a polycation in vitro. AB - Effect of the polycation on oxidative phosphorylation in the rat liver mitochondria has been studied. Both oxygen uptake and coupled phosphorylation were progressively inhibited by increasing concentration of the polycation, as observed with NAD-linked substrates, succinate and ascorbate+TMPD which activates the terminal part of the respiratory chain. NADH oxidase, NADH dehydrogenase and cytochrome oxidase were strongly inhibited by the polycation, 80-90% of the activity being lost at an inhibitor concentration of 100 microM. Succinate oxidase and succinate dehydrogenase were inhibited 60-66% at 100 microM concentration of the polycation. The polycation inhibited the uncoupler 2,4 dinitrophenol stimulated ATPase activity both in presence and absence of Mg2+ ions. The polycation also inhibited salt-induced volume change. PMID- 8509126 TI - Barley oxalate oxidase immobilized on zirconia-coated alkylamine glass using glutaraldehyde. AB - A method for immobilizing barley oxalate oxidase to zirconia coated alkylamine glass through the process of glutaraldehyde coupling has been described. The immobilized enzyme retained 97.2% of the specific activity, with a conjugation yield of 6.63 mg/g support and showed an increase in optimum pH. The Km value of immobilized enzyme was unaltered but Vmax was decreased compared to free enzyme. The conjugated enzyme was stable at 4 degrees C for 2 years. A number of inorganic ions and metabolic substances did not denature the immobilized enzyme. The clinical importance of this work is demonstrated. PMID- 8509127 TI - A simple chemical method for the oxidation of beta-hydroxybutyrate; application of the method for the estimation of ketone bodies. AB - A simple one-step method employing potassium persulphate as an oxidising agent in presence of catalyst, Ag2+, for the oxidation of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) has been developed and standardized. Under the condition of assay, beta-OHB (0.079-0.395 microM) was quantitatively transformed to AcAc. The reaction linearity was observed from 0.079 to 0.634 microM. Optimum conditions were: pH, 6.2; temp., 40 degrees C; persulphate saturation, 40% and catalyst, 1.82 mM. Under the experimental condition, no reversal of inhibition caused by chloride (22.96 mM) was observed at Ag+ concentrations (9.09 and 18.18 mM), while higher conc. of Ag+ (27.27 mM) caused significant reversal of inhibition (about 60%). The maximum reversal of inhibition was achieved at Ag+ (36.36 mM). The level of ketone bodies, when estimated by the present method, was greatly enhanced during starvation period and about 2- and 12-fold higher level of ketone bodies was observed (compared to control) in rats fasted for 24 and 48 hr respectively. PMID- 8509128 TI - Immobilization of amyloglucosidase. AB - Enzymatic hydrolysis of starch for the production of glucose syrups of various compositions has assumed considerable commercial significance due to the extensive application of these syrups in food and beverage industries. Hydrolysis of starch to glucose involves liquefaction of the gelatinized starch with acid or thermostable alpha-amylase followed by saccharification to glucose by amyloglucosidase. Large scale saccharification of liquefied starch to glucose using soluble enzyme is time consuming and requires 48-72 hr at pH 4.5 and 55-60 degrees C. Since, by replacing soluble amyloglucosidase with immobilized enzyme, it is possible to reduce the conversion time, several methods have been tried to obtain a highly active and stable immobilized preparation capable of converting high concentrations of liquefied starch to glucose. However, till today, immobilized amyloglucosidase has not found industrial application as no immobilized system has shown high temperature stability and conversion efficiency comparable to that of the soluble enzyme. PMID- 8509129 TI - Insulin-like effects of bis-glycinato oxovanadium (IV) complex on experimental diabetic rats. AB - The insulin-like activity of bis-glycinato oxovanadium (IV) complex on experimental diabetes has been studied. Rats made diabetic with streptozotocin, after one month, were fed ad libitum with bis-glycinato oxovanadium (IV) complex (30 mg/100 ml) for fifteen days. The altered blood glucose, urea, cholesterol, triglycerides, liver glycogen and the activities of liver enzymes such as hexokinase, lactate dehydrogenase and fructose-1, 6-bisphosphatase, were reverted to normal levels in bis-glycinato oxovanadium (IV) complex treated diabetic rats, thereby suggesting for the insulin-mimetic effect of bis-glycinato oxovanadium (IV) in experimental diabetes. PMID- 8509130 TI - Gangliosides inhibit T-lymphocyte proliferation by preventing the interaction of interleukin-2 with its cell surface receptors. AB - Gangliosides are known to be actively shed from tumour cell membranes, and increased levels of circulating gangliosides may cause tumour-induced T lymphocyte immunosuppression in vivo by interfering with the actions of interleukin-2 (IL-2). We have investigated the effect of gangliosides on the interaction of IL-2 with its cell surface receptors (IL-2R). Gangliosides inhibited IL-2-stimulated proliferation in synchronized populations of the IL-2 dependent cell lines CTLL-2 and HT-2. The immunosuppressive effect was most effective when gangliosides were added during the first 4 hr after IL-2 stimulation, indicating that they acted early in the IL-2 signalling pathway. Inhibition could be completely overcome by exogenous IL-2, suggesting that gangliosides inhibited growth solely by competing with IL-2R for available IL-2. In support of this proposal, gangliosides induced a concomitant dose-dependent decrease in binding of [125I]IL-2 to high-, medium- and low-affinity IL-2R. Ganglioside-treated cells recovered their high-affinity [125I]IL-2 binding after washing. The glycolipids also prevented chemical cross-linking of [125I]IL-2 to the p55/p75 complex, as well as to both IL-2R alpha (p55) and IL-2R beta (p75) independently. A thin-layer chromatography overlay technique was used to demonstrate that IL-2 binds directly to gangliosides, but not to simple neutral glycolipids or acidic lipids. Taken together, these findings indicate that gangliosides directly block the interaction of IL-2 with IL-2R, and may explain, in part, the immunosuppressive activities of gangliosides in vivo. PMID- 8509131 TI - Characterization of a macrophage lineage cell colony-stimulating factor produced by thymic myoid cells. AB - Thymic myoid cells produced macrophage lineage cell stimulatory factors. Activities were separated into two factors on DEAE-Sepharose CL-6B chromatography: one eluted at lower concentrations of NaCl and the other at higher concentrations of NaCl. The latter fraction was purified to homogeneity with an apparent molecular weight of 100,000. This factor stimulated the growth of macrophage-lineage cells from the bone marrow, but not that of granulocytes, megakaryocytes or erythroblasts. The 100,000 MW factor was able to induce Ia antigens on proliferating bone marrow cells. These results suggest that myoid cell-derived 100,000 MW factor plays significant roles in the generation of Ia positive macrophage lineage cells which are important for T-cell development in the thymus. PMID- 8509132 TI - Differential control of major histocompatibility complex class II I-Ek alpha protein expression in the epithelium and in subsets of lamina propria antigen presenting cells of the gut. AB - In the gut, both the villus epithelium and cells of macrophages and dendritic cell lineages of the lamina propria and Peyer's patches express major histocompatibility complex (MHC) class II glycoproteins and have the potential to present soluble protein antigen. Using mice transgenic for the X and Y promoter deletion mutants of the gene encoding the I-Ek alpha class II protein we have shown: that an intact promoter is essential for expression of I-Ek alpha on the epithelium and lamina propria macrophages; that only the Y box is essential for expression by lamina propria dendritic cells; and that dendritic cells in Peyer's patches are phenotypically more restricted than in the lamina propria and express I-Ek alpha under different regulatory control mechanisms. The results show that different inductive mechanisms exist for class II in distinct mucosal cell populations and provide a model for the analysis of differential antigen handling in the gut mucosa. PMID- 8509133 TI - Modulation of interferon-gamma-induced major histocompatibility complex class II and Fc receptor expression on isolated microglia by transforming growth factor beta 1, interleukin-4, noradrenaline and glucocorticoids. AB - Interleukin-4 (IL-4) enhances Fc receptor (FcR) expression on isolated rat brain microglia and peritoneal macrophages but has little effect on major histocompatibility complex (MHC) class II antigen expression. In contrast transforming growth factor-beta 1 (TGF-beta 1) causes a reduction in expression of MHC class II on macrophages and of FcR on both cell types. Both microglia and peritoneal macrophages demonstrate enhanced expression of FcR and MHC class II on treatment with interferon-gamma (IFN-gamma). The effect of IL-4 or TGF-beta 1 in combination with IFN-gamma, added either sequentially or simultaneously, has been investigated. TGF-beta 1 down-regulates IFN-gamma-induced effects in both microglia and macrophages when present before or during the activation stage. In combination, IL-4 and IFN-gamma can be additive or antagonistic, depending on their concentrations and the sequence in which cells are exposed to the cytokines. Non-cytokine mediators present during stimulation, such as noradrenaline, dexamethasone and corticosterone, are also potent inhibitors of IFN-gamma-induced activation of microglia and macrophages. PMID- 8509134 TI - Phospholipids coupled to a carrier induce IgG antibody that blocks tumour necrosis factor induction by toxic malaria antigens. AB - Phospholipid-containing antigens of malaria parasites stimulate macrophages to secrete tumour necrosis factor (TNF), induce hypoglycaemia and are toxic to mice. This TNF induction is inhibited by antisera made against the antigens, the inhibitory activity of which can be removed specifically by adsorption to phosphatidylinositol (PI) liposomes. Although the same was true of antisera made against PI, the inhibitory activity of antisera made against some other phospholipids appeared to be directed against a common determinant, probably the phosphate ester head group. We have shown previously that the activity of all the antisera was associated mainly with IgM and was not boosted by repeated injections of the antigens. To try and induce a secondary response against the parasite antigens using non-toxic molecules, mice were immunized with various phosphorylated compounds coupled to keyhole limpet haemocyanin (KLH). Three injections of PI-KLH or of phosphatidylserine (PS) coupled to KLH induced significantly higher titres of inhibitory antibody than one; furthermore, the inhibitory activity was mainly in the IgG fraction. The antisera did not inhibit TNF induction by lipopolysaccharide (LPS) or lipoteichoic acid. However, antisera against PS-KLH, though not PI-KLH, inhibited the induction of TNF by the phospholipid, platelet-activating factor (PAF). These antisera, and antisera from mice immunized with phospho-threonine or galactosamine-1-phosphate conjugated to KLH, contained inhibitory antibodies of differing specificities. Mice immunized with PI-KLH, PS-KLH or phospho-threonine-KLH did not develop hypoglycaemia when challenged with the parasite toxic antigens. These results indicate that the antigenicity of non-toxic analogues can be dramatically enhanced by coupling to a protein carrier. PMID- 8509135 TI - Interleukin-9 potentiates the interleukin-4-induced IgE and IgG1 release from murine B lymphocytes. AB - Interleukin-9 (IL-9) is a mouse T-cell-derived cytokine that supports the growth of mucosal type mast cells suggesting its role in the regulation of type I hypersensitivity reactions. Therefore the possible effect of IL-9 on the in vitro regulation of IL-4-induced IgE and IgG1 releases in the mouse was investigated. In this report, we present evidence that IL-9 potentiated IL-4-induced IgE and IgG1 releases from lipopolysaccharide (LPS)-primed murine B lymphocytes, whereas IL-9 alone was ineffective. The potentiating effect of IL-9 is specific for IgE and IgG1 since no effect on IgM production was observed. This potentiating effect was neither related to an enhanced cell viability, nor to an alteration of the IL 4-induced expression of class II antigens by murine B cells. Besides the fact that IL-9 increased the number of IgG1-secreting cells, this cytokine might also enhance immunoglobulin release on a cell basis. Taken together, these data suggest that IL-9 plays an in vitro regulatory role in antibody synthesis, probably via a direct action on murine B lymphocytes. PMID- 8509136 TI - Prevention of pristane-induced arthritis by the oral administration of type II collagen. AB - This is the first demonstration of a role for type II collagen in pristane induced arthritis. Pretreatment with soluble type II collagen either lowers or raises the subsequent incidence and severity of pristane-induced arthritis. These effects are dependent upon both the dose and route of administration of the soluble type II collagen. Increasing doses of orally administered type II collagen lowered both the incidence and severity of pristane-induced arthritis. Conversely, increasing doses of intraperitoneally administered type II collagen increased both the incidence and severity of arthritis. This exacerbation of pristane-induced arthritis was accompanied by elevated B- and T-cell responses to type II collagen. These findings highlight the importance of the site at which antigen is encountered in influencing subsequent immune responses and extend the observations of the use of orally administered antigens to ameliorate experimental autoimmunity. PMID- 8509137 TI - Neurofilament expression in human T lymphocytes. AB - The expression of intermediate filaments in normal cells is mainly determined by their embryonal developmental origin. Flow cytometry using monoclonal antibody RT97 demonstrated that neurofilament was detectable in the human HuT 78 T-cell line and on resting T lymphocytes. Expression was greatly increased on lymphocytes activated for 3 days with phorbol ester. Western blotting confirmed the presence of the 200,000 MW form of neurofilament in T lymphocytes. Stimulation of peripheral blood T cells with phorbol myristate acetate (PMA) or with anti-CD3 monoclonal antibodies resulted in a marked increase in detection of phosphorylated neurofilament on Western blotting. Stimulation of HuT 78 cells with anti-LFA-1 resulted in redistribution of neurofilament from a perinuclear spheroid core into dendritic processes. These data indicate that T cells activated through the T-cell receptor associated complex express an intermediate filament usually associated with neurally derived cells. The finding that neurofilament expression and organization are regulated by T-cell surface molecules suggests a role for this intermediate filament in T-cell function. PMID- 8509138 TI - The effect of interferon-gamma, interleukin-4 and immunoglobulin receptor cross linking of monocytes on allergen-specific T-cell response. AB - Modulation of the proliferative responses of an allergen-specific human Th2 cell line by cytokine-treated monocytes was examined. The response of this cell line to the specific allergen, Amb a V (from short ragweed pollen), increased following the addition of interleukin-1 beta (IL-1 beta). However, in the presence of exogenous interferon-gamma (IFN-gamma), there was greater than 40% reduction in the responsiveness of these T cells. The addition of IL-1 beta did not reverse the inhibitory effect of IFN-gamma. To determine the primary target cell type for IFN-gamma, autologous monocytes were pretreated with IL-4, IFN gamma, or medium alone, and used as antigen-presenting cells (APC). We showed that the responses of T cells to Amb a V were significantly down-regulated in the presence of autologous monocytes pretreated with IFN-gamma, but not for monocytes pretreated with IL-4. Similar inhibitory effect of IFN-gamma was confirmed using a human T-cell line specific for a ragweed allergen, Amb a I, and a human T-cell clone raised against ragweed extract. Cross-linking of CD23 (Fc epsilon RII) on monocytes pretreated with IFN-gamma increased this inhibitory effect in an additive fashion, but, in the absence of IFN-gamma treatment, such cross-linking had no effect. These inhibitory effects were not due to alterations in the surface expression of HLA-DR on the monocytes, and the addition of exogenous IL-1 beta was unable to reverse these effects. In similar experiments, cross-linking of CD64 (Fc gamma R) on monocytes showed no significant effects. In conclusion, IFN-gamma is important in regulating the function of monocytes involved in Th2 cell responses to allergens. IL-4 treatment, as well as cross-linking of FcR of monocytes, have no direct effect on such response. PMID- 8509139 TI - Identification of two moieties of beta-endorphin with opposing effects on rat T cell proliferation. AB - In a previous study we demonstrated that beta-endorphin (beta-end) may stimulate rat T-cell proliferation via triggering of non-opioid receptors, whereas this stimulatory effect is abrogated by interaction of beta-end with opioid receptors. In the present study we provide evidence for this dualistic nature of beta-end by the identification of stimulatory and inhibitory sites of beta-end with the use of peptide fragments. The fragments beta-end6-31 and beta-end 18-31, which both lack the opioid receptor binding N-terminal sequence, enhanced rat T-cell proliferation when added directly to the cultures. By contrast, the peptide fragments beta-end24-31 and beta-end28-31 did not stimulate proliferation. Peptides and fragments containing the N-terminal part, i.e. methionine-enkephalin (met-enk), alpha-endorphin (alpha-end), gamma-endorphin, the fragment beta-end1 27, and the intact beta-end, did not influence proliferation by themselves. However, the addition of met-enk or alpha-end to T cells that had been stimulated by the fragments beta-end6-31 or beta-end18-31 resulted in the abrogation of the stimulating effect. These data further support the hypothesis that beta-end is a peptide with a dualistic nature: its C-terminal moiety enhances T-cell proliferation, whereas this stimulatory effect can be prevented by peptides that possess the N-terminal enkephalin sequence. PMID- 8509140 TI - Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. AB - A large proportion of intestinal intraepithelial lymphocytes (IEL) comprises alpha beta and gamma delta T-cell receptor (TcR)-bearing T cells. The numbers of alpha beta and gamma delta IEL are reported to be very different between germ free and conventional microbial conditions. In this study, we investigated the kinetics of both types of TcR-bearing cells after microbial colonization in germ free mice and the influence of thymus deprivation on IEL populations during the microbial association process. Immediately after association with microbes in germ-free animals, the number of alpha beta TcR-bearing IEL gradually increased. Fourteen days after microbial association the number of alpha beta IEL equalled that of gamma delta TcR-bearing IEL. Approximately 1 month after microbial association, the number of alpha beta IEL was several times greater than that of gamma delta IEL, having almost reached the level in conventional mice reared in a conventional animal room after birth. On the other hand the number of gamma delta IEL hardly changed throughout this microbial association process. Two-colour analysis involving anti-alpha beta TcR and anti-Lyt-2 or Lyt-3 antibodies showed that the major fraction of IEL that increased after microbial association comprised alpha beta TcR-bearing T cells expressing CD8 antigen composed of a homodimer of alpha-chains, which was not detected in other gut associated lymphoid tissues (GALT) such as Peyer's patch, mesenteric lymph node and lamina propria tissue. The number of alpha beta T cells in these GALT increased within 1 week more quickly than that of IEL. The increase in alpha beta IEL after microbial association was not prevented by thymectomy. These results strongly suggest that the progenitors of alpha beta TcR-bearing IEL expand outside the thymus in response to microbial colonization in germ-free mice. PMID- 8509141 TI - Expression of the CMRF-35 antigen, a new member of the immunoglobulin gene superfamily, is differentially regulated on leucocytes. AB - A new monoclonal antibody, CMRF-35, has been generated that recognized a 224 amino acid cell surface protein which is a novel member of the immunoglobulin gene superfamily. The antibody, raised against large granular lymphocytes (LGL), stains LGL, monocytes, macrophages and granulocytes but not platelets or erythrocytes. In addition, a subset of peripheral blood T lymphocytes (26.6 +/- 13.4% CD5+ cells) and B lymphocytes (13.7 +/- 6.8% CD20+ cells) stained with CMRF 35 but tonsil T and B cells were essentially negative. Expression of the CMRF-35 antigen (Ag) on different leucocyte populations was markedly influenced by stimulation of the cells with mitogens and cytokines. Activation of peripheral blood T cells with phytohaemagglutinin (PHA), or phorbol myristate acetate (PMA) and calcium ionophore (CaI) led to a decrease in the proportion of CMRF-35+ T lymphocytes. In contrast, PHA activation of tonsil T lymphocytes resulted in an increase in CMRF-35 Ag expression (47.1 +/- 1.5% CD5 cells at 6 days). An increase in CMRF-35 Ag was also seen on phorbol ester and CaI-activated tonsil B cells. No change in CMRF-35 expression on natural killer (NK) cells occurred following activation with interleukin-2 (IL-2) but the CMRF-35 Ag was down regulated following Fc receptor stimulation. A moderate increase in CMRF-35 expression occurred during monocyte-macrophage differentiation and the expression of the Ag on monocytes was differentially regulated by interferon-gamma (IFN gamma). This regulation of the CMRF-35 Ag on the leucocyte surface suggests that the molecule has an important function common to diverse leucocyte types. PMID- 8509142 TI - The SKW 6.4 line of human B lymphocytes specifically binds and responds to vasoactive intestinal peptide. AB - Vasoactive intestinal peptide (VIP1-28) is a neuromediator recognized by high affinity receptors on human lymphocytes, which inhibits T-cell proliferation and cytokine secretion, and suppresses immunoglobulin production by mitogen stimulated mixed mononuclear leucocytes. The direct interactions of VIP1-28 with B cells were studied in the SKW 6.4 line of EBV-transformed human B cells, that express a mean (+/- SD) of 6116 +/- 969 receptors for [125I]VIP1-28 with a mean Kd of 59 nM, that decreases to 12 nM after exposure to phorbol 12-myristate 13 acetate (PMA). The secretion of IgM by SKW 6.4 B cells stimulated optimally with 100 ng/ml of PMA, but not unstimulated secretion of IgM, was suppressed significantly by 10(-12) M to 10(-9) M VIP1-28 and up to a mean maximum (+/- SD) of 40 +/- 2% by 10(-10) M VIP1-28. VIP1-28 elicited concomitant increases in intracellular cyclic AMP up to a mean maximum of 163% at 10(-10) M VIP1-28. The requirement for specific signal transduction by the occupied VIP receptors to inhibit IgM secretion was demonstrated by the lack of effect of VIP4-28 on both cyclic AMP concentration and IgM secretion, despite the equal affinity of binding of VIP4-28 and VIP1-28. The effects of VIP on immunoglobulin secretion by stimulated mixed mononuclear leucocytes thus may be due in part to a direct action on B cells. PMID- 8509143 TI - B cells do not present antigen covalently linked to microspheres. AB - B cells have been shown to present antigen to T cells very efficiently through their capacity to capture antigens by their membrane immunoglobulin. This direct cognate interaction of T and B cells results in the proliferation and differentiation of B cells. This concept has been established using soluble proteins. However, most of the antigens to which the immune system is exposed are included in complex particulate structures such as bacteria or parasites. The capacity of B cells to present these large and complex antigens is still unclear. To address this question we have studied the presentation by trinitrophenyl (TNP) specific B cells of the same antigen TNP-KLH (keyhole limpet haemocyanin), either in a soluble form or covalently linked to poly(acrolein) microspheres, from 0.25 to 1.5 microns in diameter. In the presence of irradiated splenocytes or purified macrophages as a source of antigen-presenting cells (APC), KLH-specific T cells proliferated in response to soluble TNP-KLH or to TNP-KLH coupled to beads. In contrast, TNP-specific memory B cells were totally ineffective in presenting the TNP-KLH beads to KLH-specific T cells whereas they presented very efficiently soluble TNP-KLH. Similar results were obtained with the A20 B lymphoma or with lipopolysaccharide (LPS)-activated TNP-specific B cells. These results therefore indicate that B cells are unable to present large size particulate antigens such as bacteria or parasites. PMID- 8509144 TI - Immunoglobulin G binding sites on the human foetal intestine: a possible mechanism for the passive transfer of immunity from mother to infant. AB - In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for IgG on the placenta. However, amniotic fluid contains IgG of maternal origin, and transfer of swallowed IgG into the circulation from the foetal intestine represents another potential pathway of passive immunization. In this study we assayed for a foetal intestinal IgG receptor to support the hypothesis of this alternate pathway of antibody transfer. Microvillous membrane (MVM) from small bowel of aborted foetuses (18 weeks gestation) were probed with [125I]IgG to detect specific IgG binding sites. Binding was pH dependent and was maximal at pH 6. Competitive inhibition of the binding of [125I]IgG was noted with the addition of increasing amounts of unlabelled IgG. Scatchard analysis showed one binding site with a dissociation constant of 1.58 x 10(-7), similar to that of the IgG receptor described on the suckling rat intestine. The binding of labelled IgG to the human MVM receptor was Fc mediated. These observations provide evidence for an Fc receptor on the human foetal intestine. PMID- 8509145 TI - Murine complement receptor gene expression: Cr2 gene transcripts are depressed during a high dose microbial challenge. AB - The murine Cr2 gene encodes mRNA that produce two protein products predicted to be approximately 145,000 M(r) (Cr2-145) and 190,000 M(r) (Cr2-190). All cells examined which express the Cr2 gene produce transcripts encoding both the Cr2-145 and Cr2-190 proteins: both transcripts are constitutively expressed by mature B cells. To determine if Cr2 expression could be altered by activating splenic B cells, splenic cultures were incubated with lipopolysaccharide (LPS) and cell surface Ig chains were cross-linked with anti-mu. In the presence of LPS and anti mu both Cr2 and Oct-2 transcripts were diminished while the control beta-actin transcript levels remained unchanged. However, when LPS alone was added, only the Cr2 transcript levels were diminished. To test if these findings could be reproduced in vivo, animals were provided with a peritoneal injection of either Escherichia coli or Listeria monocytogenes and transcript levels analysed. The quantities of both Cr2 transcripts, as well as those encoding Oct-2, were substantially reduced in splenocytes and peripheral lymphatic tissues obtained from these infected mice while those encoding the mouse Crry protein, the B-cell marker CD19 and beta-actin remained unchanged. These data suggest that when confronted with a major bacterial infection, murine B cells respond by shutting down synthesis of transcripts encoding the Cr2 and Oct-2 gene products. PMID- 8509147 TI - EFIS: the growing danger of self-satisfaction with numbers. PMID- 8509146 TI - Distinct IgG1 and IgG3 subclass responses to two streptococcal protein antigens in man: analysis of antibodies to streptolysin O and M protein using standardized subclass-specific enzyme-linked immunosorbent assays. AB - The IgG subclass composition of antibodies to two streptococcal protein antigens in sera following infection was analysed by enzyme-linked immunosorbent assays (ELISA). The assays were standardized using 5-iodo-4-hydroxy-nitrophenacetyl (NIP)-specific chimeric antibodies, to permit quantitative comparisons between subclasses. Antibodies to streptolysin O (SLO) were predominantly IgG1, with only minor contributions from the other subclasses. In contrast, antibodies to M protein were distributed between the IgG1 and IgG3 subclasses, and in approximately half the sera IgG3 predominated. The ratio of IgG1:IgG3 was greater for SLO than for M protein in 22/23 sera. Little or no IgG4 antibody was detected to either antigen. Functional affinities of the IgG1 and IgG3 antibodies, determined by inhibition ELISA, were comparable for the two antigens. The demonstration that two protein antigens encountered during streptococcal infection elicit antibody responses with markedly different subclass profiles has implications for IgG subclass regulation and vaccine development. PMID- 8509148 TI - Adhesion and costimulation of proliferative responses of human gamma delta T cells by interaction of VLA-4 and VLA-5 with fibronectin. AB - The very late antigens, VLA-4 and VLA-5 belong to the beta 1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+CD4-CD8- gamma delta TCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL 2 receptor) but not resting CD25low gamma delta T cells specifically adhere to FN. The binding capacity is inhibited by the synthetic peptide GRGDSP which inhibits adhesion mediated by VLA-5 and a functional mAb directed against the alpha 4 subunit. Most FN binding is mediated by VLA-4. Additionally, resting gamma delta T cells cultured on coimmobilized anti-TCR delta 1 mAb and FN or the 40 kDa fragment (which contains the adhesion site in the IIICS domain recognized by VLA-4) for 96 h in the absence of exogeneous IL-2 showed significant increase in proliferation when compared to that of resting gamma delta T cells cultured on immobilized anti-TCR delta 1 mAb alone. Also expression of CD25 was significantly enhanced on cells cultured on coimmobilized anti-TCR delta 1 mAb and FN, indicative of T cell activation. Cross-linking of VLA-4 and VLA-5 molecules costimulated expansion of resting gamma delta T cells induced by cross-linked TCR delta 1. These results suggest that the gamma delta T cell beta 1 integrins, VLA 4 and VLA-5, may function in a dual capacity as signalling and adhesion molecules. PMID- 8509149 TI - Effects of interleukin-1, -2, -4, -6, interferon-gamma and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells. AB - Human vascular endothelial cells (HUVEC) exhibit various immunological functions, i.e. expression of HLA class-II antigens after incubation with IFN-gamma or antigen presenting function. It has also been reported that HUVEC are able to produce IL-1, IL-6, GM-CSF and immunologically active cleavage products of arachidonic acid. In our study we investigated whether various cytokines, namely IL-1, IL-2, IL-6, GM-CSF and IFN-gamma, do alter the proliferative capacity of HUVEC, the production of van Willebrandt factor (vWF) and the expression of MHC class-II antigens. HUVEC were prepared by the collagenase digestion of human umbilical veins. Monolayers of cells were incubated with cytokines in different concentrations for 24 and 48 h. IFN-gamma inhibits the HUVEC [3H]thymidine uptake in a dose-dependent manner. Suppression of proliferation (40.1%) could be observed after 24 h incubation with 100 U IFN-gamma/ml. IL-1 was a more effective inhibitor of HUVEC proliferation (54% at 10 U/ml and 24 h incubation and 48.4% after 48 h) than IFN-gamma. IL-6 and GM-CSF showed an increasing effect on proliferation with 226% and 151% of the control group, respectively. IFN-gamma after an incubation period of 12 h and IL-1 after 24 h reduced the vWF content by about 30%. Bright MHC class-II expression was induced only by IFN-gamma. In conclusion, some of the immunoregulative cytokines might play an important role in the control of HUVEC proliferation. PMID- 8509150 TI - Molecules in earthworm coelomic fluid that bind anti-IgA and anti-IgG, but not anti-IgM. AB - Coelomic fluid from the earthworm Lumbricus terrestris is known to contain immunoactive cells and molecules involved in immune defense. To assess the ability of such molecules to form precipitating complexes with anti-human immunoglobulins, radial immunodiffusion experiments were conducted. Anti-human IgG, anti-human IgA, and anti-human IgM were the three immunoglobulins examined. Earthworm coelomic fluid was found to contain molecules that bind anti-IgA and anti-IgG. No precipitation reactions were observed with anti-IgM. Earthworm coelomic fluid diluted 1:8 still formed precipitating complexes with anti-IgA and anti-IgG. Elucidation of the earthworm binding site on anti-IgG and anti-IgA could make earthworm coelomic fluid a valuable reagent in immunological, chemical and biological research. PMID- 8509151 TI - Demonstration that anti-phospholipid auto-antibodies react with both anionic and zwitterionic phospholipids. AB - The specificity of anti-phospholipid auto-antibodies present in the serum of systemic lupus erythematosus patients towards the phospholipids has been studied by two different methods. The antibodies have been characterized either after affinity purification or by inhibition experiments. Our results clearly demonstrate that anti-phospholipid auto-antibodies recognize all phospholipids, whatever their polar head. PMID- 8509152 TI - In vitro stimulation of human fetal lymphocytes by mitogens and interleukins. AB - Human lymphocytes derived from fetal spleen and liver were studied for their capacity to respond to mitogens and interleukins using different in vitro models (cell volume increase, [3H]thymidine incorporation, Ig secretion). Although the number of mature B and T cells in the fetal liver preparations remained nearly constant [Settmacher et al. (1991) Immunobiol. 182, 256], only lymphocytes obtained from fetal organisms before the 25th week of gestation could respond to some of the polyclonal stimulators (PWM, anti-CD3 + IL-2, SAC + IL-2, SAC + IL-4) tested, whereas cells obtained after that period failed. In the fetal spleen, however, with increasing percentages of mature B and T cells during fetal development, a growing ability to respond to mitogens was registered, which, however, did not achieve the values found for the adult spleen material. PMID- 8509153 TI - Alterations of T-cell: extracellular matrix proteins interactions in psoriasis. AB - Recent data indicate that extracellular matrix proteins (collagens, fibronectin) co-stimulate T-cell lymphoproliferative responses in vitro. We have studied the co-stimulatory activities of those proteins in patients with psoriasis, a disease in which T cells infiltrating the skin are continuously exposed to collagen and fibronectin. CD3-triggered T-cell proliferative responses were lower in psoriasis but could be enhanced by collagens I and IV and fibronectin. Interestingly, collagen-I-dependent co-stimulation was markedly decreased in patients with psoriasis, while there was a trend towards the enhancement of collagen-IV-induced responses. Those disturbances were most frequently seen in patients with active and widespread lesions. It appears that abnormalities of extracellular matrix protein-derived signals could play a role in the immunopathology of psoriasis. PMID- 8509154 TI - Thymic nurse cell clone supports the differentiation of CD4-8- thymocytes into CD4+8+ thymocytes in vitro. AB - A previously reported thymic nurse cell clone, TNC-R3.1 could form a unique complex with isolated adult mouse CD4-8- (DN) thymocytes and greatly sustained the cell viability of DN thymocytes in suspension culture. In addition, the TNC R3.1 clone supported the differentiation of DN thymocytes into CD4+8+ (DP) thymocytes in a short-term culture. Addition of IL-7 into the coculture markedly enhanced DN thymocyte-TNC interaction and induced the proliferation and differentiation of DN thymocytes, though IL-7 alone did not induce the differentiation of DN thymocytes. Separation of DN thymocytes from TNC-R3.1 monolayer using a Millicell caused a great inhibition of the DN thymocyte differentiation, suggesting that direct contact between TNC-R3.1 cells and immature thymocytes was required for the differentiation of DN thymocytes. The kinetics study demonstrated that DN thymocytes started to differentiate into DP thymocytes through CD3-CD4+J11d+ intermediate cells 8-12 h after the initiation of the culture with TNC-R3.1 plus IL-7. The generation of DP thymocytes became maximal 20 h after coculture and gradually decreased thereafter. Furthermore, we demonstrated that TNC-R3.1 could support the differentiation of CD3+CD4+CD8- or CD3+CD4-CD8+ thymocytes from CD3-CD4-CD8- thymocytes in the presence of IL-7 and IL-2. These data indicate that our established in vitro culture system mimics the early stage of the intrathymic T cell developing pathway. PMID- 8509155 TI - Effects of administration of anti-CD4 and anti-CD8 monoclonal antibodies on Mycobacterium paratuberculosis infection in intragastrically challenged mice. AB - In this study, we examined the roles of CD4+ and CD8+ cells in resistance to experimental paratuberculosis. Mice received purified anti-CD4 or anti-CD8 monoclonal antibodies before intragastric challenge with Mycobacterium paratuberculosis and on a biweekly basis for six months. This resulted in sustained depletion of CD4+ and CD8+ cells as verified by flow cytometry analysis of spleen cells from M. paratuberculosis infected mice. Depletion of CD4+ or CD8+ cells did not enhance fecal shedding of M. paratuberculosis, bacillary multiplication in the liver and ceca, nor histopathologic damage to the intestinal tract, mesenteric lymph nodes, spleen and liver. These data suggest that cells other than CD4+ or CD8+ cells are important for host defense in experimental paratuberculosis. PMID- 8509156 TI - The role of CD8-positive lymphocytes in the control of HIV-1 infection of peripheral blood mononuclear cells. AB - The role of CD8-positive lymphocytes from HIV-1-seropositive individuals in the inhibition of HIV-1 replication in CD4-positive lymphocytes, either from HIV-1 seropositive or -seronegative individuals, has been described. It has been suggested that CD8-positive lymphocytes isolated from HIV-1-seropositive individuals are 'primed' against certain HIV-1 antigens, hence inducing HIV-1 specific resistance. In the present studies, we show that CD8-positive lymphocytes from HIV-1-uninfected individuals also induce a significant decrease in HIV-1 replication from peripheral blood mononuclear cells (PBMC) acutely infected with HIV-1 in vitro. Unfractionated PBMC from 16 HIV-1-seronegative individuals were infected with HIV-1. In parallel experiments, PBMC from these individuals were depleted of CD8-positive lymphocytes. Viral replication was measured by a syncytia-formation assay, as well as by measuring HIV-1 p24 antigen levels in the culture supernatants on day 10 post-infection. Removal of CD8 positive lymphocytes resulted in the increased replication of HIV-1 in vitro. Reconstitution with syngeneic CD8-positive lymphocytes to CD8-positive lymphocyte depleted wells resulted in significant decreases in HIV-1 replication. Reconstitution with allogeneic CD8-positive lymphocytes or supernatants from syngeneic or allogeneic CD8-positive lymphocyte cultures also resulted in some decrease in HIV-1 production, but it was not statistically significant. The status of HIV-1 replication in unfractionated, CD8-positive lymphocyte-depleted and CD8-positive lymphocyte-reconstituted PBMC cultures was further confirmed at the level of HIV-1 transcription. In situ hybridization of cultured cells, with a biotinylated HIV-1 gag probe, revealed increased numbers of cells actively transcribing HIV-1-specific RNA in the CD8-positive lymphocyte-depleted cell cultures, as compared with unfractionated PBMC. Thus, removal of CD8-positive lymphocytes from PBMC obtained from HIV-1-seronegative individuals resulted in a significant enhancement of HIV-1 replication in vitro. PMID- 8509157 TI - Clinical relevance of antibodies to Ro/SS-A and La/SS-B in subacute cutaneous lupus erythematosus and related conditions. AB - Ro/SS-A autoantibodies are frequently associated with subacute cutaneous lupus erythematosus, neonatal lupus erythematosus and Sjogren's syndrome. The Ro/SS-A autoantigen is a ribonucleoprotein complex consisting of at least four protein components and four small cytoplasmic RNA components designated hY RNA 1, 3, 4 and 5. Three of the Ro/SS-A peptides have been isolated and cloned. The function of this ribonucleoprotein complex is as yet unknown. PMID- 8509158 TI - IDDM patients' sera recognize a novel 30-kD pancreatic autoantigen related to chymotrypsinogen. AB - We have examined, by western immunoblot analysis, the sera of 16 insulin dependent diabetes mellitus patients (IDDM) for the presence of autoantibodies against proteins extracted from islet-cell enriched preparations of normal human pancreata. A novel putative autoantigen recognized by late stage IDDM patients sera was identified, and its amino acid sequence was partially determined. Islets of Langerhans were partially purified by a modified collagenase digestion procedure, and subsequent protein extracts were fractionated by one-dimensional or two-dimensional polyacrylamide gel electrophoresis (1-D or 2-D SDS-PAGE). Immunoblot analysis revealed a 30-kD species which was recognized by 4 of 16 IDDM patients sera, but none of 16 normal sera. The 30-kD protein, appeared as a single band on 1-D SDS-PAGE, but was resolved on 2-D gel electrophoresis as several distinct protein species with different isoelectric points (pI's), ranging from 7 to 9. The amino terminal sequence of one such species was partially determined by microsequencing, and the second through the fourteenth amino acids were found to be identical to the corresponding sequence in human chymotrypsinogen. The fifteenth through the eighteenth amino acids were different from the known chymotrypsinogen sequence. This region corresponds with the site that is cleaved to activate chymotrypsinogen. Based on the size and sequence homology, this antigen appears to be related to chymotrypsinogen. We conclude that this 30-kD species may be an autoantigen in some late stage IDDM patients. PMID- 8509159 TI - Biosynthesis of colony-stimulating factor-1 (CSF-1) by mesangial cells of autoimmune mice. AB - The amounts of colony-stimulating factor (CSF-1) produced by the mesangial cells of the kidney may be of pivotal importance in determining the outcome of nephritis, since CSF-1 activates macrophages, and macrophages have been shown to perform an important scavenger function in removing immune complexes which localize in the kidney. To test this hypothesis, the present study examined CSF-1 production by mesangial cells of the autoimmune MRL/MpJ-lpr-lpr strain of mice and also of their normal congenic MRL/MpJ-++ counterparts. It was found that mesangial cells of autoimmune mice produced diminished amounts of functional CSF 1 when measured by a bioassay, giving validation to the hypothesis proposed. Of interest, expression of CSF-1 mRNA was discordantly increased in mesangial cells of the MRL-lpr autoimmune mice. Based on current knowledge of the pathway for CSF 1 synthesis and secretion, it would appear that there may be a block in the post transcriptional pathway for CSF-1 biosynthesis in autoimmune mesangial cells. PMID- 8509160 TI - Fish optic nerve oligodendrocytes support axonal regeneration of fish and mammalian retinal ganglion cells. AB - Segments from adult fish and rat retinae were explanted on myelin-marker expressing oligodendrocytes derived from the regenerating goldfish optic nerve. Fish axons grew in high density and even rat retinal axons regenerated to considerable length on the surface of the fish oligodendrocytes, suggesting that this type of fish glia has axon-growth promoting surface components that exert their influence across species boundaries. One interesting surface component of the fish oligodendrocytes as demonstrated here is the E 587 antigen, which is related to the L1 family of cell adhesion molecules. In long term cocultures of oligodendrocytes and retinal axons, the fish glial cells were found to enwrap rat axons. This suggests that the oligodendrocytes of the regenerating goldfish optic nerve/tract may, despite striking differences, represent the equivalent to mammalian optic nerve oligodendrocytes. PMID- 8509161 TI - The inhibition of oligodendrocytic differentiation of O-2A progenitors caused by basic fibroblast growth factor is overridden by astrocytes. AB - The inhibition of differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitors into oligodendrocytes caused by basic fibroblast growth factor (bFGF) can be overcome by non-O-2A lineage cells present in the optic nerve and by astrocytes purified from cerebral cortices. Although purified O-2A progenitors grown in the presence of bFGF for up to 6 days were inhibited from differentiating into oligodendrocytes, O-2A progenitors growing in heterogeneous optic nerve cultures did not show a similar inhibition of differentiation. The factor(s) responsible for overriding the inhibitory effects of bFGF appeared to be secreted by astrocytes, as extensive generation of oligodendrocytes was seen in cultures of purified O-2A progenitors exposed to bFGF+ medium conditioned by purified astrocytes (ACM). In addition, purified O-2A progenitors displayed a remarkable sensitivity to bFGF, which extended at least down to concentrations of 0.03 ng/ml, a concentration of < 2 x 10(-12) M. At a bFGF concentration of just 0.1 ng/ml, this mitogen still promoted DNA synthesis in as many O-2A progenitors as in cultures exposed to 1-30 ng/ml of this growth factor, but exhibited a reduced ability to promote DNA synthesis in oligodendrocytes. In addition, although concentrations of bFGF as low as 0.03 ng/ml were a potent stimulator of DNA synthesis in O-2A progenitors, application of this amount of bFGF no longer inhibited the differentiation of progenitors into oligodendrocytes as effectively as application of higher bFGF concentrations. Thus, the induction of DNA synthesis by bFGF can be uncoupled from the inhibition of differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509162 TI - A blood-derived attachment factor enhances the in vitro growth of two glial cell types from adult cockroach. AB - Reactive glial cells from chemically-lesioned areas of the central nervous system (CNS) of adult cockroaches (Periplaneta americana) have been grown in vitro on a substrate of fibronectin. This paper reports the enhancement of growth that is achieved when blood cells, serum, or medium conditioned by a 2-h incubation with blood cells are used as an alternative substrate. Glial cells rapidly grew out from connective explants to form extensive radial mats of cells linking up with those from adjacent explants on each of the blood-derived substrates. In addition to supporting the growth of reactive glial cells, characterised by their long, thin, branching morphology, these substrates also revealed the presence of a second type of glial cell, not previously found on fibronectin. Such cells, derived from ganglionic explants, behaved in a very different way to the reactive glia, initially spreading out to form a flattened sheet of phase-bright cells, before migrating away over the culture surface. The growth-enhancing effects of this blood-derived factor may play a role in the events following damage to the insect CNS, where it is known that the entry of blood cells into the lesion site is an important precursor to the rapid and structured repair seen in this system. PMID- 8509163 TI - Muscarinic acetylcholine receptor-expression in astrocytes in the cortex of young and aged rats. AB - The present report describes the cellular and subcellular distribution pattern of immunoreactivity to M35, a monoclonal antibody raised against purified muscarinic acetylcholine receptor protein, in astrocytes in the cerebral cortex of young and aged rats. Most M35-positive astrocytes were localized in the superficial layers of the cortex and part of the corpus callosum. At the ultrastructural level, immunoprecipitates were localized in the Golgi complexes, but the nucleus, rough endoplasmic reticulum, mitochondria, and microfilaments were generally free of labeling. Labeling was also present associated to the cell membrane, although without the characteristic immunoreactive postsynaptic membrane thickening found in neuronal structures. In aging rats of 30-34 months, the number of M35-labeled astrocytes doubled, whereas the neuronal staining slightly decreased in the same region in half of the animals studied. Fluorescent double-labeling for M35 and GFAP, an astrocytic microfilament protein, revealed that all M35-positive glial cells express GFAP and, conversely, that almost all GFAP glial cells were M35 immunostained. Based on the high incidence of coexpression of mAChRs and GFAP, both proteins may be functionally linked to each other. Rough semiquantitative estimates revealed that in young adult rats the GFAP/M35-immunoreactive astrocytes made up approximately one fifth of all cortical astrocytes. An important aspect of the presently demonstrated immunoreactivity of astroglia to mAChR proteins is its labeling in situ instead of in tissue culture. This finding may further support investigation, e.g., on anatomical relations of astroglia with neuronal and vascular elements, and its reactivity in experimental conditions. PMID- 8509164 TI - Lymphokine induction of rat microglia multinucleated giant cell formation. AB - Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules. PMID- 8509165 TI - Distribution of metallothionein in the human central nervous system. AB - The distribution of metallothionein (MT), a metal-binding protein, was examined immunohistochemically in the normal human brain and spinal cord. Paraffin embedded brain tissue from three patients who had died from a non-neurological disease and were free of histopathological central nervous system alterations were processed. The results of the present study demonstrate that MT is readily detectable in a subgroup of astrocytes in the normal human brain. MT staining is most intense on grey matter astrocytes that bear short stout processes and which probably represent protoplasmic astrocytes. Using anti-MT and anti-glial fibrillary acidic protein immunostaining, we could demonstrate two subpopulations of astrocytes that were mutually exclusive. The functional significance of MT expression in protoplasmic astrocytes is not entirely clear. Metal detoxification is only one of the many postulated functions of MT. The finding that staining for MT permits subtyping of astrocytes may be of great importance in glia research and surgical pathology of the human brain. PMID- 8509166 TI - Changing indications for liver transplantation. AB - Improvement in liver transplantation over the past decade has resulted in questions regarding indications and contraindications, patient selection, timing, and cost. PMID- 8509167 TI - Advances in liver transplantation. PMID- 8509168 TI - Liver transplantation for chronic hepatitis C viral infection. AB - HCV infection is a common cause of both liver disease in patients undergoing liver transplantation and postoperative damage to the allograft. Emerging techniques to diagnose this infection have enabled us to understand the relation between pretransplantation and post-transplantation infection and to study the consequences of infection in these immunocompromised patients. The use of anti HCV-positive donors is highly controversial and will remain so until the natural history of post-transplantation HCV infection is known. Study of the relation between histologic damage and levels of HCV replication will likely provide insights into the biology of this virus and mechanisms of hepatic damage. PMID- 8509169 TI - Liver transplantation for the alcoholic patient. AB - A review of the data from the University of Michigan and other transplant centers suggests that the outcome of liver transplantation, when considered as either mortality or psychological morbidity, is similar for alcoholics and nonalcoholics alike. The process to select alcoholic patients for transplantation has been outlined herein. Care is taken to identify alcoholic patients in whom long-term abstinence is likely, but a fixed period of abstinence prior to transplantation does not appear to be a useful selection tool. Resource utilization by alcoholics undergoing liver transplantation does not appear to differ from that by nonalcoholic recipients. Carefully conducted long-term studies are necessary to assess the natural history of liver allografts in alcoholics. PMID- 8509170 TI - Liver transplantation for fulminant hepatic failure. AB - In conclusion, the availability of liver transplantation has dramatically advanced the management of fulminant hepatic failure. A major responsibility of the gastroenterologist/hepatologist involved in the care of patients with liver failure is early decision making regarding likelihood of spontaneous recovery and consideration toward referral to a transplantation center. In particular, patients with exposure to drugs or toxins (other than acetaminophen); patients with presumed non-A, non-B hepatitis; children or older patients; patients with prolonged jaundice; profoundly jaundiced patients; or patients with severe coagulopathy should be given the highest consideration for urgent transplantation. Supportive care should take into account the potential complications of bleeding, sepsis, cerebral edema, renal failure, and respiratory failure. Such complications are the major limiting factors that prevent patients with fulminant hepatic failure from undergoing liver transplantation and contribute to the majority of postoperative deaths among patients who undergo transplantation. If these issues are heeded, and in light of emerging therapeutic modalities and surgical innovations, it is anticipated that ongoing improvement of the overall outcome of patients with fulminant hepatic failure will continue to be seen. PMID- 8509172 TI - Clinical application of liver-related liver transplantation. AB - The success of liver transplantation as a clinical therapy has led to a critical shortage of donor livers. The ethical basis for living-related liver transplantation (LRT) has been extensively studied and is outlined in this article. LRT has been performed with high success rates at several centers in the industrialized world and can be considered routinely for children needing livers. Extension of this procedure to adults will represent an important innovation and is currently under study. PMID- 8509171 TI - Liver transplantation for hepatitis B. PMID- 8509173 TI - Nonsurgical management of biliary tract disease after liver transplantation. AB - It is not possible to describe every possible biliary tract complication that occurs after liver transplantation. It is important to be aware that almost anything can happen and that the biliary tree should be evaluated in any patient with unexplained allograft dysfunction. Frequently, the endoscopist can aid not only in the determination of the problem but often in its resolution as well. PMID- 8509174 TI - Bone disease in liver transplant recipients. AB - Osteopenic bone disease with atraumatic fracturing is a major cause of morbidity in liver transplant recipients. The course of bone loss after transplantation is biphasic, consisting of an early phase with acute loss of bone followed by stabilization or even improvement in bone density. The pathophysiology of the osteopenia is poorly understood, and treatment is supportive. Osteonecrosis is a second, less common skeletal complication after liver transplantation, assumed to be related to the use of corticosteroids. PMID- 8509175 TI - Growth and nutritional management of pediatric patients after orthotopic liver transplantation. AB - The overall results of pediatric liver transplantation continue to be increasingly encouraging and rewarding. The careful development of long-term follow-up protocols addressing nutrition and growth are vital components of the comprehensive care of this patient population. PMID- 8509176 TI - New immunologic insights into mechanisms of allograft rejection. AB - Our current understanding of liver allograft rejection indicates that multiple cellular interactions, involving a variety of cell-associated and soluble mediators, are critical to the response. The extravasation and localization of recipient immune cells to the allograft is dependent on recognition and interaction of complementary adhesion molecules expressed on circulating leukocytes and endothelium. Similar receptor-ligand pairs can also augment the binding of effector cells to target tissue within the allograft. Inflammatory mediators such as IL-1, IL-6, TNF-alpha, and IFN-gamma produced within the allograft can increase the local expression of adhesion molecules and thereby promote the entry of specific and nonspecific cells. The TCR expressed on T lymphocytes has the potential to recognize MHC antigens expressed on the allograft in many different forms. Thus, the T cell response to graft-associated alloantigens appears to be complex and dynamic. The production of T cell-derived cytokines is central to the activation and maturation of effector cells within the allograft. The identification of cytotoxic mediators such as serine protease and MBP within rejecting human allografts supports the role of cytotoxic T cells and eosinophils as effector cells. Undoubtedly, the development of genetically manipulated animal models will serve to further elucidate our understanding of the cellular mechanisms of graft rejection. PMID- 8509177 TI - An economic analysis of liver transplantation. Costs, insurance coverage, and reimbursement. AB - Liver transplantation is an expensive surgical procedure. In 1988, the median procedure charge was $145,795. Charges varied according to numerous prognostic variables. Insurance reimbursement often fell short of billed charges. Nonetheless, relative to other medical and surgical procedures, liver transplantation is cost-effective. PMID- 8509178 TI - Advanced trauma life support. PMID- 8509179 TI - Role of magnetic resonance imaging in the assessment of spinal injuries. AB - Magnetic Resonance Imaging (MRI) examination was carried out on 44 patients who had spinal injuries with neurological involvement. The technique provided valuable information about the nature of the injuries and, in particular, about the state of the spinal cord. The appearances of the cord on MRI ranged from normal, to oedema, to more severe damage such as cord haemorrhage or transection or, in later cases, myelomalacia. The appearance of the cord on MRI correlated strongly with both the severity of the neurological deficit and also the degree of subsequent recovery. In the assessment of the acute spinal injury, MRI has been shown to be a good prognostic indicator; it may also help to identify which patients are likely to benefit from early decompression. PMID- 8509180 TI - Neck sprains after road traffic accidents: a modern epidemic. AB - This study was carried out to determine the incidence of soft tissue injuries of the cervical spine after road traffic accidents and to assess whether the incidence had changed with time. The results show that there has been a progressive increase since 1982 in the number of patients seen in accident and emergency departments with a neck sprain after road traffic accidents. The results suggest that the increase is not necessarily due to the introduction of seat belts, but that the relentless increasing epidemic may be due to other factors. PMID- 8509181 TI - Use of polyglycolic acid mesh with a new double pursestring technique in renal trauma: an experimental study. AB - Repair of major kidney lacerations with conventional techniques is extremely difficult and 'through and through' suturing is associated with further loss of viable tissue because it promotes scarring. In this study, we investigate the haemostatic and viable parenchyma salvaging effect of an alternative, new wrapping technique in an experimental renal trauma model. This resulted in immediate haemostasis in all 25 animals, while the same injury caused excessive haemorrhage with 50 per cent mortality in eight untreated controls. This technique differs from other wrapping methods because no additional suturing for the application of PAM or haemostasis is required. It is an easy, rapid procedure which decreases the operating time and may allow successful repair in major lacerations of the kidney. PMID- 8509182 TI - Impairment scores of type III open tibial fractures. AB - The results of 17 patients with type III open tibial fractures were judged retrospectively by using the Guides to the Evaluation of Permanent Impairment. The fractures were divided into types IIIA (N = 7), IIIB (N = 5) and IIIC (N = 5) according to Gustilo et al. (1984). The impairment scores of these patients were compared with those after a through-knee amputation (36 per cent impairment) or a below-knee amputation (28 per cent impairment). The average impairment scores of the three groups were: IIIA 7.1 per cent, IIIB 19 per cent, IIIC 18.4 per cent. The impairment score of salvaged type III open tibial fractures, for each group, IIIA, IIIB and IIIC, was lower than that after a below-knee or through-knee amputation. PMID- 8509183 TI - Interobserver variation using the AO/ASIF classification of long bone fractures. AB - A comprehensive classification system has been proposed by the AO/ASIF Foundation for the classification of long bone fractures. After an explanatory talk and with the aid of an illustrated pamphlet, 18 orthopaedic surgeons were asked to classify 10 long bone fractures according to the AO system. Three of the participating surgeons had previous experience of the classification system. After individual classification, a consensus classification was derived and the results of the individual and consensus codings were compared. Only 32 per cent of all codings agreed with the final consensus. There was no difference between the surgeons with previous experience of the system (66 per cent) and novice coders (69 per cent) in the number of inaccurate codes when compared with the consensus codes. Reasons for error in coding are discussed. It is recommended that if the AO system is used for the purposes of research and computer-based audit, a consensus of opinion is used as the basis of classification. PMID- 8509184 TI - Internal fixation of metacarpal and phalangeal fractures with AO minifragment screws and plates: a prospective study. AB - In a prospective study, 43 patients with 47 metacarpal or phalangeal fractures with significant displacement, rotation, angulation and/or instability were treated with internal fixation using AO minifragment screws and plates. In all fractures an anatomical reduction was achieved. Postoperatively all metacarpal fractures were protected by means of a plaster, in which motion was allowed, whereas all phalangeal fractures were treated by means of a soft bandage. At a review after a mean period of 28 months, 31 patients with 35 fractures out of 34 patients with 38 fractures had regained excellent recovery of total active flexion (92 per cent). Three patients had a poor recovery of total active flexion; one had an infection, the other two were operated on 6 and 14 days after their injury, whereas the mean delay between injury and operation was 3 days. All patients not reviewed had regained good or 100 per cent function. PMID- 8509185 TI - Toddler's fracture of the calcaneum. AB - Calcaneal fractures in very young children are thought to be rare. We report on seven calcaneal fractures in children under the age of 36 months in the absence of a history of significant injury. In five cases plain radiology was normal, but the diagnosis was reached using scintigraphy. We suggest that this is not such a rare injury, and that wider use of scintigraphy will assist in making the diagnosis. The prognosis of this injury is excellent. PMID- 8509186 TI - A review of 40 acetabular fractures: the importance of early surgery. AB - This study demonstrates the importance of early surgery in the management of acetabular fractures. A total of 40 acetabular fractures in 39 patients was treated by open reduction and internal fixation over a 5-year period. Of these, 26 fractures were assessed at over 1 year and up to 4.25 years postoperatively by the Merle D'Aubigne/Postel hip score. Sixteen patients (61.5 per cent) had a good result (16-18), five patients (19.25 per cent) a moderate result (11-15) and five (19.25 per cent) a poor result (0-10). The quality of the clinical result correlated closely with the quality of the reduction of the fracture. The timing of surgery was found to be directly related to the quality of the clinical result. Patients with poor results had been operated on at an average of 17 days after injury, while those with good results had undergone an operation at an average of 11 days. Rapid referral to a regional centre with the necessary facilities and expertise to manage these fractures is recommended in those patients where an operation may be indicated. PMID- 8509187 TI - The Seidel humeral locking nail: an anatomical study of the complications from locking screws. AB - The Seidel locking nail was inserted into the humeri of 20 cadavers. Subsequent dissection showed that the proximal locking screws had damaged the circumflex nerve or biceps tendon in eight of the cases. PMID- 8509188 TI - Disassembly of the short version Pugh nail-plate device: an illustrative case. AB - A case is presented of disassembly of the Pugh nail-plate device. Our recommendations are given for prevention of this occurrence. PMID- 8509189 TI - K-wire fixation of supracondylar humeral fractures in children: results of open reduction via a ventral approach in comparison with closed treatment. AB - The morbidity and functional outcome of K-wire fixation of dislocated supracondylar humeral fractures in children after open reduction through a ventral approach were studied, using the results after closed reduction as a golden standard. A series of 49 children were evaluated retrospectively. Of these, 46 children could be included in the study, of whom 35 were treated with closed reduction (group A) and 11 were treated with open reduction via a ventral approach (group B). All fractures were splinted in plaster for 3 weeks postoperatively. Thereafter free active motion of the elbow was permitted. Our data show that open reduction via a ventral approach carries no morbidity. The time for full functional recovery was equal in both groups. Only one out of 11 patients showed mild varus deformity after open reduction, while this slight malalignment occurred in five of 35 patients after closed reduction. The final anatomical and functional results did not differ between the two groups. It can be concluded that K-wire fixation of dislocated supracondylar fractures in children gives excellent results and that open reduction via a ventral approach is a logical, safe and elegant alternative, if closed reduction fails. PMID- 8509190 TI - Initial axial computerized tomography examination in chest injuries. AB - A total of 41 injured patients examined by both chest radiography and axial computerized tomography (CT) of the chest within the first 24 h after the accident were reviewed. In all, 10 patients died, eight from cerebral or cervical injuries, two from haemorrhage. Of the 27 cases with a haemothorax, 13 were seen on a chest radiograph. In only one case was a haemothorax seen on CT large enough to warrant intervention. CT revealed one minor pneumothorax. Nine patients already treated with a chest drain had some residual air demonstrated by CT, two being significant pneumothoraces. CT showed 28 cases of lung contusion as opposed to 23 on a chest radiograph. Of five cases with a mediastinal haematoma, three were seen on a chest radiograph, including the only patient with aortic rupture. Clinically important pathology was revealed in ordinary chest radiographs. Contusions, small pneumothoraces and minor effusions were sometimes overlooked. CT scan of the chest alone is rarely warranted in the injured patient, given a liberal indication for chest drainage and ready access to arch aortography. PMID- 8509191 TI - Comparing the mortality and morbidity of cemented and uncemented hemiarthroplasties. AB - A series of 207 consecutive patients admitted to Aberdeen Royal Infirmary over a 1-year period with a diagnosis of displaced subcapital fracture of the neck of the femur were treated by hemiarthroplasty with either a cemented Hasting or an uncemented Monk bipolar prosthesis. Patients were reviewed at an average of 19 months and differences in mortality and morbidity assessed. We found that there was a significant perioperative mortality in the cemented group and no perioperative mortality in the uncemented group. There was no significant difference in the morbidity or complication rate in the two groups, although surviving patients appeared significantly more satisfied with the cemented Hasting prosthesis. PMID- 8509192 TI - Burns in children: do casualty officers get it right? AB - It is often said that casualty officers are unable to assess burns accurately. This prospective study examines this, proving the point and offering basic suggestions for improvements. PMID- 8509193 TI - Cervical spine fractures due to spear tackles in two Rugby league players. PMID- 8509194 TI - Self-injection with mercury. PMID- 8509195 TI - Neuroleptic malignant syndrome: case report in a multiple trauma patient. PMID- 8509196 TI - Replica hand guns: not so safe! PMID- 8509197 TI - Ocular gunpowder injury: retained intralenticular gunpowder. PMID- 8509198 TI - Intra-articular sesamoid dislocation of the interphalangeal joint of the great toe. PMID- 8509199 TI - Bilateral sacroiliac fracture-dislocation. PMID- 8509200 TI - Intra-articular migration of broken trochanteric wires. PMID- 8509201 TI - Subdural haematoma and factor XII deficiency in a Chinese infant. PMID- 8509202 TI - An unusual indication for removal of an internal fixation plate. PMID- 8509203 TI - Rhabdomyolysis: a neglected priority in the early management of severe limb trauma. PMID- 8509204 TI - A case of non-union of the medial cuneiform. PMID- 8509205 TI - Lap-style seat belt associated with high cervical cord injury in a child. PMID- 8509206 TI - Inferior (subacromial) dislocation of the outer end of the clavicle. PMID- 8509207 TI - Post-traumatic axillary artery thrombosis dissolution with low-dose intra arterial streptokinase. PMID- 8509208 TI - Closed intramedullary distal locking made easier. PMID- 8509209 TI - Plastic bullets: significant risk of serious injury above the diaphragm. PMID- 8509210 TI - A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. AB - A new murine monoclonal antibody (MAb), E-9, has been raised using tissue cultured human umbilical vein endothelial cells. The antigen recognized by this MAb is a peptide of 170 kDa under non-reducing conditions and 96 kDa under reducing conditions. MAb E-9 showed marked heterogeneity in its distribution in various tissues. The antigen recognized by it was present in vascular endothelial cells of all tumours, foetal organs and in regenerating and inflamed tissues. It stained a few normal tissues. However, with the exception of tonsils, staining tended to be weak and limited to a few blood vessels, as revealed by double staining using pan-endothelial antibody (CD31) and antibody to von Willebrand factor, another marker of vascular endothelium. Surprisingly, blood vessels within the placental villi were completely negative. The function of the antigen recognized by MAb E-9 is not known, but its evaluation and use should increase our understanding of angiogenesis. PMID- 8509211 TI - Tumour spectrum in hereditary non-polyposis colorectal cancer (HNPCC) and in families with "suspected HNPCC". A population-based study in northern Italy. Colorectal Cancer Study Group. AB - Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up. PMID- 8509212 TI - Usage of T-cell receptor V beta chain genes in fresh and cultured tumor infiltrating lymphocytes from human melanoma. AB - Tumor-infiltrating lymphocytes (TIL) freshly obtained from human malignant melanomas as well as the same TIL grown in the presence of interleukin 2 (IL2) were studied for gene expression of the T-cell receptor (TCR) variable beta regions (V beta). To perform the TCR-V beta analysis, total RNA was isolated from TIL and reverse-transcribed into cDNA, which was then amplified by PCR using 22 different 5' primers specifically recognizing the sequences of 20 V beta gene families and a 3' primer annealing to the constant region of the beta chain. The TCR-alpha constant region (C alpha) gene was co-amplified as a standard for the calculation of the percentage of each TCR-V beta gene expressed. The frequency of individual V beta regions expressed on TIL was computed from the ratio of cpm V beta to cpm C alpha for each V beta region in relation to the total of all 22 ratios. With fresh TIL obtained from 8 different melanomas, oligoclonal distribution of V beta genes expressed on TIL was observed, in comparison with a broader and unrestricted distribution seen with peripheral-blood T cells of 8 normal individuals. The oligoclonal patterns of V beta-gene expression in fresh melanoma TIL were distinct in every tumor. Several of the V beta-genes usually expressed in normal PBL were not expressed in fresh TIL in melanoma TIL cultured in the presence of IL2 and IL4 and in the absence of autologous tumor (AuTu) or antigen-presenting cells for 23 to 65 days, selection of T-cell lines expressing a restricted number of V beta genes occurred. Although in 4/5 TIL cultures this selection involved the V beta 7 gene, no relationship could be established between V beta gene expression in fresh TIL and that in T-cell lines outgrowing in long-term cultures. Selection in culture of CD3+CD8+ T-cell lines with V beta gene expression restricted to 1 or 2 V beta families did not correlate with the presence or level of AuTu cytotoxicity mediated by these T cells. The results indicate that in TIL cultures random selection of T-cell lines with reactivity not relevant to AuTu may account for poor expression or loss of AuTu cytotoxicity by most TIL cultured long-term in the presence of cytokines and in the absence of specific antigenic stimulation. PMID- 8509213 TI - Monoclonal antibody 4D3 detects small intestinal mucin antigen (SIMA)- glycoprotein in the serum of patients with colorectal cancer. AB - We have developed a sensitive ELISA using MAb 4D3 for the detection of a novel epitope on Small Intestinal Mucin Antigen (SIMA) and report here that SIMA is present in the serum of patients with colorectal cancer. SIMA has been shown to occur in tissue from a high proportion of patients with colorectal cancer. SIMA derived from serum was similar to tissue-derived SIMA: both eluted in the void volume of a Superose 6 column indicating a molecular weight above 5,000 kDa and they exhibited similar buoyant densities on CsCl gradients. The ELISA was most reliable after pre-treatment of serum with 0.4 M perchloric acid to remove interfering substances. The upper limit for SIMA in normal serum was set as the mean plus 2 standard deviations determined from a group of 97 healthy control subjects. In a sample of 113 patients with colorectal cancer, SIMA serum levels were elevated in 15% of patients with Dukes' Stage A, 38% with Stage B, 32% with Stage C and 75% with Stage D colorectal cancer. SIMA serum levels were compared with those of the widely used tumor marker, carcinoembryonic antigen (CEA). The SIMA assay detected a significant number of sera that were not detected by the test for CEA. We propose that SIMA will prove to be a valuable serological tumor marker, in combination with CEA and other tumor markers, for the detection of colorectal cancer. PMID- 8509214 TI - Differential chemosensitivity of local and metastatic human gastric cancer after orthotopic transplantation of histologically intact tumor tissue in nude mice. AB - We have established a metastatic model of human gastric cancer using orthotopic transplantation of histologically intact tissue in nude mice, and have used this model to evaluate the effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) against SC-I-NU, a human stomach cancer line. One quarter or one-half maximum tolerated doses (MTDs) of 5-FU or MMC resulted in a significant reduction of stomach tumor growth, while liver metastases were not reduced, possibly due to suppression of natural killer (NK)-cell activity by both drugs. On the other hand, when combined with OK-432, half MTDs of 5-FU and MMC significantly reduced liver metastases, with synergistic reduction of stomach tumor growth, possibly reflecting a rescue of NK-cell activity by treatment with OK-432. This metastatic model of human stomach cancer shows that locally growing and metastatic tumors may have different chemosensitivities, and provides the opportunity to test both with various treatment regimens. PMID- 8509215 TI - Increasing incidence of both major histological types of esophageal carcinomas among men in Sweden. AB - Although a rare tumor form, there is evidence that the incidence of esophageal adenocarcinomas is increasing in Western Europe and the US. The aim of this nationwide population-based study was to describe the secular trends in the incidence rates of adenocarcinoma and squamous-cell carcinoma of the esophagus over a 28-year period from 1960 to 1987. The Swedish Cancer Registry, complete to more than 95%, was used to identify the cases. The percentage verified by histology rose from 89% to 98%. The age-standardized incidence rate of adenocarcinoma increased in males from 0.5 per 10(5) in 1960-63 to 1.1 per 10(5) in 1984-87, corresponding to an average annual increase of 1.5%. In females the incidence remained stable around 0.2 per 10(5). The age-standardized incidence rate of squamous-cell carcinoma in males increased from 2.9 to 4.0 per 10(5), corresponding to an average annual increase of 1.0%. In females the rate decreased from 1.4 to 1.2 per 10(5), corresponding to an annual average decrease of 0.5%. The male/female ratio was 4.6 for adenocarcinoma and 2.7 for squamous cell carcinoma of the esophagus. Since the incidence rates of squamous-cell carcinoma of the esophagus and of adenocarcinoma seem to be rising, there is a great need for well-planned analytical epidemiological studies of these tumor locations, taking the histological type into consideration. PMID- 8509216 TI - p53 mutations in sporadic adrenocortical tumors. AB - Non-familial human adrenocortical adenomas and carcinomas were screened for mutations in exons 5-8 of the p53 tumor suppressor gene by single-strand conformation-polymorphism (SSCP) analysis, followed by direct sequencing of PCR amplified DNA. Point mutations in codons 12, 13 and 61 in H-ras, K-ras and N-ras proto-oncogenes were similarly assessed by direct DNA sequencing. Three out of 15 primary adrenocortical carcinomas (20%) contained a mis-sense point mutation in the conserved regions (exons 5 and 8) of the p53 gene. Mutations were located in codon 157 (GTC-->TTC; Val-->Phe), codon 163 (TAC-->AAC; Tyr-->Asn), and codon 273 (CGT-->TGT; Arg-->Cys). The mutation in codon 157 was detected in the primary tumor as well as in brain and lymph-node metastases. Among 18 adrenocortical adenomas, there was only a single non-miscoding mutation in codon 295 (CCT-->CCC; Pro-->Pro). These data suggest that mutational inactivation of the p53 gene occurs in a minority (20%) of sporadic adrenocortical carcinomas and that these mutations constitute a late event in the multi-step process of malignant transformation. No ras mutations were detected in any of these tumors, suggesting that these genes are not involved in the development of tumors originating from the adrenal cortex. PMID- 8509217 TI - Biodistribution study of 99mTc-labeled LDL in B16-melanoma-bearing mice. Visualization of a preferential uptake by the tumor. AB - Since there is strong evidence of a preferential LDL accumulation in tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of 99mTc LDL in tumor imaging with B16-melanoma-bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99mTc labeled LDL than with 125I labeled LDL. Since technetium-99m remains trapped in the cells, 99mTc-LDL is a well-adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor-bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing of the animals) showed a 1.81-fold increase in uptake by the tumor as compared to the liver and a 28-fold increase as compared with corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non-invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. 99mTc-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients. PMID- 8509218 TI - Intracellular glutathione heterogeneity in L1210 murine leukemia sublines made resistant to DNA-interacting anti-neoplastic agents. AB - Intracellular glutathione (GSH) content was measured by flow cytometry using monochlorobimane (mBCl) and by the enzymatic assay in a set of 6 sublines of murine L1210 leukemia cells made resistant to DNA-interacting agents having distinct mechanisms of action: L-phenylalanine mustard (L-PAM), 1,3-bis(2 chloroethyl)-I-nitrosourea (BCNU), cisplatin (DDP), N-deformyl-N-(4-N,N-bis(2 chloroethylamino) benzoyl) distamycin A (FCE 24517), doxorubicin (DX) and 3' deamino-3' (2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762). A significant correlation was demonstrated between the mean intracellular mBCl fluorescence values measured by flow cytometry and levels of GSH measured by the classical enzymatic assay, despite the possible influence of glutathione-S-transferases and of other thiols on the mBCl fluorescence. Although less specific, the flow cytometric method is more informative than the enzymatic assay, allowing detection of fluorescence distributions, which we proved to be characteristic of each subline. In order to assess a procedure enabling a quantitative analysis to be made of intercellular GSH heterogeneity, we propose the use of appropriate thresholds and parameters of the mBCl flow cytometric distribution. By use of this analysis procedure, distinct types of alterations, with respect to the heterogeneity distribution of the parental L1210 cell line, have been evidenced in resistant cells. A uniform increase in mBCl fluorescence was observed among cells of the sublines resistant to L-PAM and FCE-24517. The mean mBCl fluorescence increase in sublines resistant to DX and DDP was due to a higher number of cells with fairly high mBCl fluorescence, but still within the range spanned by the parental cell line. A less heterogeneous mBCl fluorescence distribution was found in the L1210 subline resistant to FCE 23762, which was, however, similar to a cloned sensitive line. Though GSH was linked to the principal cause of drug resistance only in the L-PAM-resistant cell line, alterations in heterogeneity, as detected by mBCl fluorescence distributions, were found in 5 out of 6 resistant lines. PMID- 8509219 TI - Inhibition of glycolysis and mitochondrial respiration of Ehrlich ascites carcinoma cells by methylglyoxal. AB - The effect of methylglyoxal (MG) on the aerobic glycolysis of Ehrlich ascites carcinoma (EAC) cells has been tested. Methylglyoxal inhibited glucose utilization and glucose 6-phosphate (G6P) and L-lactate formation in whole EAC cells. Methylglyoxal strongly inactivated glyceraldehyde 3-phosphate dehydrogenase (GA3PD) of the malignant cells, whereas MG has little inactivating effect on this enzyme from several normal sources. Methylglyoxal also inactivated only the particulate hexominase of the EAC cells, but this inactivation was less pronounced than the effect on GA3PD. Methylglyoxal has little inactivating effect on glucose 6-phosphate dehydrogenase (G6PD), and no effect on L-lactate dehydrogenase (LDH) of the malignant cells. Glucose-dependent L-lactic acid formation of EAC-cell-free homogenate was strongly inhibited by MG, but when GA3PD of normal cells was added to this homogenate, significant lactate formation was observed even in the presence of MG. Methylglyoxal also inhibited the respiration of EAC-cell mitochondria. Respiration of mitochondria isolated from liver and kidney of normal mice, however, remained unaffected. As a consequence of the inhibition of glycolysis and mitochondrial respiration, the ATP level of the EAC cells was drastically reduced. Studies reported herein strongly suggest that the tumoricidal effect of MG is mediated at least in part through the inhibition of mitochondrial respiration and inactivation of GA3PD, and this enzyme may play an important role in the high glycolytic capacity of the malignant cells. PMID- 8509220 TI - Transformation of mouse fibroblasts with the oncogenes H-ras OR trk is associated with pronounced changes in drug sensitivity and metabolism. AB - Malignant activation of oncogenes ras or trk is implicated in a number of solid tumors and leukemias. We determined the chemosensitivity profile of wild-type mouse NIH-3T3 fibroblasts, and that of NIH-3T3 lines transformed by the H-ras (S2 721) and trk (106-632) oncogenes, against 11 different drugs from various classes. Differences in sensitivity were related to drug accumulation and metabolism. Both ras- and trk-transformed cell lines were less sensitive to cisplatin (CDDP) and doxorubicin (DXR) than the wild type. NIH-3T3 transformants expressing H-ras were less sensitive than those expressing trk or the wild type to the indoloquinone EO9, methotrexate and arabino-furanosylcytosine. No clear difference in sensitivity was observed for vincristine, VP-16, or the new cytidine analog 2',2'-difluoro-deoxycytidine. In both ras- and trk-transformed cell lines sensitivity to 5FU was increased moderately, but sensitivity to 5'deoxy-5-fluorouridine (5'dFUR) was increased markedly. Only the trk-transformed line NIH-3T3 was more sensitive to 2'deoxy-5-fluorouridine. Expression of P glycoprotein was not different between the 3 cell lines but DXR accumulation in both mutants was decreased, indicating a non-P-glycoprotein-associated difference in sensitivity. Conversion of 5'dFUR to 5FU (catalyzed by pyrimidine nucleoside phosphorylases) was 5-10 times higher in both mutants than in the wild type. The activity of the phosphoribosyl-transferase (direct conversion of 5FU to FUMP) was comparable, but the rate of conversion of 5FU to fluorouridine (FUR) was lower in the wild type, as well as that of 5FU to FUMP via FUR. In contrast, the activity of thymidylate synthase, the target enzyme for fluoropyrimidines, was higher in the wild-type cells. The concentrations of both purine and pyrimidine nucleotides were lower in cells expressing trk. In conclusion, transformation of cells with the H-ras or trk oncogenes can markedly influence sensitivity to several drugs and affect normal metabolism and that of several anti-cancer agents. PMID- 8509221 TI - Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines. AB - We show that flavonoids positively regulate type-II estrogen-binding site (type II EBS) levels both in MCF-7 (ER-positive) and in MDA-MB231 (ER-negative) breast cancer cells. Type-II EBS were measured by a whole-cell assay at 4 degrees C for 2.5 hr using [3H]-estradiol as tracer. In both cell lines the effect of quercetin (Q) was dose-related and already evident after 12 hr of Q treatment. The increase of type-II EBS levels after Q exposure requires both RNA and protein synthesis, since actinomycin D and cycloheximide completely abolished the stimulatory effect. The ability of flavonoids in inducing type-II EBS is well correlated with their relative binding affinity for type-II EBS. The flavonoid-induced enhancement of type-II EBS levels is accompanied by increased sensitivity of cancer cells to the inhibitory effect of low Q concentrations. Our data suggest that type-II EBS are ligand-regulated receptors. PMID- 8509222 TI - Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN alpha/beta therapy of Friend erythroleukemia visceral metastases. AB - Interferon alpha/beta (IFN alpha/beta) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC-injected DBA/2 beige (bg/bg) mice. Use of IFN alpha/beta-resistance FLC indicated that IFN was acting through host mechanisms in DBA/2 mice and thus pointed to a defect in some host mechanism in bg/bg mice essential for IFN's anti-metastatic action. We undertook experiments to restore in bg/bg mice the marked anti-FLC metastatic effect of IFN alpha/beta observed in DBA/2 and +/bg mice. Adoptive transfer of spleen cells from normal syngeneic mice to IFN-treated bg/bg mice was ineffective, but the transfer of splenic T lymphocytes from FLC-immunized DBA/2 or +/bg mice markedly increased the survival time of FLC-injected bg/bg mice provided that these mice were also treated with IFN alpha/beta. Neither treatment alone resulted in an increase in survival time. As few as 1 x 10(7) immune spleen cells were effective in IFN-treated FLC-injected bg/bg mice. The T-cell immune response to FLC of bg/bg mice was diminished compared with that of +/bg mice. Likewise, only combination therapy of immune spleen cells and IFN alpha/beta resulted in an increased survival time of ESb-lymphoma-injected bg/bg mice. Our results indicate the essential participation both of T-cell-mediated immune mechanisms and of IFN alpha/beta in the inhibition of FLC visceral metastases. PMID- 8509223 TI - Superantigen-induced cytokines suppress growth of human colon-carcinoma cells. AB - We have recently demonstrated that the superantigen staphylococcal enterotoxin A (SEA) conjugated to colon-carcinoma-reactive monoclonal antibodies (MAbs) directs T cells to lyse human colon-carcinoma cells, representing a potential novel tumor therapy. To further analyze the mechanism of antitumor effects of superantigen activated T cells, we compared the activity of free and MAb-conjugated SEA in a long term in vitro co-culture assay of human peripheral-blood mononuclear cells (PBMC) and colon-carcinoma cell lines. Activation of resting T lymphocytes with SEA conjugated to the colon-carcinoma-reactive MAb C215 or free SEA resulted in strong inhibition of the growth of all studied colon-carcinoma cell lines. The growth of WiDr colon-carcinoma cells was unaffected by the presence of unactivated mononuclear cells, whereas addition of pM concentrations of SEA or C215-SEA conjugate completely suppressed tumor-cell growth. The suppressive effect was mediated by both CD4+ and CD8+ T cells and required the presence of MHC-Class II+ monocytes. The inhibition of tumor-cell growth was to a large extent mediated by soluble factors present in supernatants from SEA- or C215-SEA activated mononuclear cells. Quantitation of cytokine mRNA in SEA-activated mononuclear cells by the reverse transcriptase-polymerase chain reaction (RT-PCR) revealed strong induction of mRNA encoding the cytokines IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha, TNF-beta and IFN-gamma. The use of cytokine-specific MAb demonstrated that IFN-gamma was of major importance for the tumor-growth inhibitory activity in supernatants of SEA-activated lymphocytes. Addition of recombinant cytokines to WiDr colon-carcinoma cells showed that TNF-alpha was able to act synergistically with IFN-gamma to suppress tumor-cell growth. The local production of tumor-suppressive cytokines induced by MAb-targeted superantigens is likely to be of particular relevance for inhibition of the growth of tumor cells not expressing the targeted tumor-associated antigen. PMID- 8509224 TI - Carcinogenic potential of some pesticides in a medium-term multi-organ bioassay in rats. AB - The carcinogenic potential of 5 pesticides was analyzed using a medium-term multi organ bioassay for carcinogenicity. Male F344 rats were initially treated with 3 known carcinogens (diethylnitrosamine, N-methyl-N-nitrosourea and N-bis(2 hydroxypropyl)nitrosamine) during a period of 4 weeks to induce neoplastic changes in a variety of organs, and then given one of 5 pesticides in the diet for a further 16 weeks. Neoplastic and pre-neoplastic lesions were found in the thyroid, kidney and urinary bladder with propineb, in the forestomach, kidney and thyroid with captan and folpet. The number of glutathione S-transferase placental form-positive liver-cell foci was significantly increased in the captan- and phosmet-treated groups. Based on these findings, captan and propineb can be considered as carcinogens and carcinogenicity is suspected for folpet and phosmet. These results are in concordance with reported long-term carcinogenicity for captan, folpet and propineb. Daminozide was considered not to be carcinogenic. Thus, the present assay of 20 weeks' duration is useful for the prediction of potential carcinogens. PMID- 8509225 TI - Disialoganglioside GD2 anti-idiotypic monoclonal antibodies. AB - Disialoganglioside GD2 is widely expressed among neuroblastomas, melanomas, small cell lung carcinoma, sarcomas and brain tumors. Immunity directed against this antigen may have anti-tumor utility. Since GD2 is poorly immunogenic, anti idiotypic antibodies may serve as alternative tumor vaccines. Monoclonal antibody 3F8, a murine IgG3 specific for GD2, has shown excellent tumor-targeting ability in vitro and in vivo. LOU/CN rats were immunized with 3F8 and their spleens were used in somatic-cell hybridization, using SP2/0, P3 and Y3 as fusion partners. Six anti-idiotypic (anti-id) MAbs (C2D8, Idio-2, AIG4, C2H7, C4E4, A2A6) were selected based on their reactivity with 3F8 and non-reactivity with murine IgG3 myelomas. Specificity of each anti-id was demonstrated by using various ELISA: (i) lack of direct binding to solid phase myelomas and serum proteins; (ii) inability of other myelomas to inhibit anti-id binding to 3F8; (iii) absence of cross-reactivity of other myelomas to solid-phase anti-id; (iv) lack of inhibition by anti-id of binding of other ganglioside antibodies to their antigens. Antigen specificity was further examined by inhibition of binding of 3F8 to GD2 on immuno-thin-layer chromatography, and by inhibition of 3F8 immunostaining of neuroblastoma cell lines. These 6 antibodies were demonstrated to be distinct, in view of their cross-reactivity, fusion partners and relative strength of binding to 3F8. Anti-GD2 antibodies were induced after immunization with these anti-id antibodies in C57Bl/6 mice. These rat anti-3F8-idiotypic antibodies with exquisite specificity for anti-GD2 antibodies may be useful in vaccine construction. PMID- 8509226 TI - Interaction of human malignant melanoma tumor spheroids with endothelium and reconstituted basement membrane: modulation by RGDS. AB - Tumor-cell extravasation involves sequential adhesive interactions with vascular endothelium and the subendothelial basement membrane. We have established a 3 dimensional model in vitro to simulate these events and to elucidate targets of the anti-cell-adhesive synthetic peptide RGDS. Tumor spheroids of the melanoma cell line ST-ML-12 served as models of tumor-cell emboli and were transferred onto human umbilical vein endothelial cells. To imitate the vascular anatomy, the latter were grown on reconstituted basement membranes produced by dextran stimulated bovine corneal endothelial cells. RGDS did not affect the homotypic aggregation of the tumor cells and only minimally inhibited the attachment of the spheroids to the reconstituted vessel. A short-term (20 min) inhibition of adhesion to denuded basement membranes was observed. The attachment was closely associated with damage to the endothelial cells by oxygen-derived free radicals. RGDS retarded endothelial injury for up to 3 hr. The most prominent effect was observed after penetration of the endothelium. RGDS suppressed the emigration of tumor cells from the attached tumor-cell cluster in a dose- and time-dependent fashion. After 12 hr, the inhibitory effect progressively declined. This was not due to loss of activity of the peptide, indicating a resistance mechanism in the melanoma cells. On purified components of the basement membrane, RGDS effectively inhibited the initial spheroid attachment to fibronectin and collagen IV but had no effect on attachment to laminin. By contrast, subsequent migration was significantly suppressed on all substrata. Our model permits the study of dynamic cell-cell and cell-extracellular-matrix interactions and indicates that RGDS might predominantly act on early tumor-cell locomotion after penetration of the endothelium. PMID- 8509227 TI - Dualistic effects of cis-diammine-dichloro-platinum on the anti-tumor efficacy of subsequently applied recombinant interleukin-2 therapy: a tumor-dependent phenomenon. AB - The efficacy with which disseminated SL2 and P815 tumors, in syngeneic DBA/2 mice, can be eradicated with low-dose recombinant interleukin-2 (rIL-2) therapy is about equal. Treatment (i.p.) of DBA/2 mice, injected i.p. with SL2 or P815 cells on day 0, with rIL-2 (Proleukin) on days 10 to 14 results in a cure rate of 50 to 60% in each case. The in vitro sensitivity of SL2 and P815 cells to cis diammine-dichloro-platinum [II] (cisplatin) is also comparable, although P815 appears to be slightly more sensitive. In vivo, however, therapy with cisplatin is far less effective against P815 than against SL2. In the DBA/2-SL2 model, at all doses tested, combination therapy with cisplatin (administered on day 2) and rIL-2 (administered on days 10-14) resulted in anti-tumor efficacy greater than that of either drug separately. In contrast, in the DBA/2-P815 model, cisplatin decreased the anti-tumor efficacy of subsequently applied rIL-2 therapy. As the only difference between the 2 tumor models is the tumor itself, the success of combination therapy with cisplatin and rIL-2 was dependent on tumor characteristics. We suggest that in these 2 tumor models, neither the sensitivity of these tumors to cisplatin nor their growth and dissemination patterns were responsible for the contrasting results of combination therapy in these models. Instead, tumor-dependent immune-modulating effects of cisplatin may be the cause of these effects. These immune-modulating effects may comprise (a) effects of cisplatin on the tumor cells, resulting in changes in their susceptibility to immune effector cells, or changes in their immunogenicity; (b) activating or suppressive effects of cisplatin on immune effector cells; or (c) a combination of these effects. These effects could then either synergize or antagonize with the immune activating properties of rIL-2. PMID- 8509228 TI - Generation and control of metastasis in experimental tumor systems; inhibition of experimental metastases by a tilorone analogue. AB - The role of the chemical compound RMI 10,874DA (3,6-bis[2-(dimethylamino) ethoxyl]-9H-xanthene-9-one dihydrochloride) in the abrogation of the metastatic spread of tumor cells was studied. Pre-treatment of BALB/c mice with the RMI 10,874DA compound (referred to below as tilorone analogue) completely eliminated lung colonization of an H-2-negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental metastasis assay. Other murine tumors, including H-2-positive and H-2-negative chemically induced fibrosarcoma clones and B16 melanoma, were also sensitive to the treatment; orally administered tilorone analogue given one day before the i.v. injection of tumor cells markedly inhibited lung colonization. The effect was not due to direct toxicity of tilorone analogue on tumor cells, but instead it was dependent on NK cells; this was suggested by the finding that anti-asialo GM, treatment of mice abrogated the effect of tilorone analogue. Kinetic studies of splenic NK activity in tilorone-treated mice showed a rapid boosting of NK-cell activity, the greatest stimulation occurring the day before removal of splenocytes for 51Cr-release assay against YAC-I target cells. These kinetics correlated with the inhibition of in vivo lung colonization after tilorone analogue treatment. Inhibition of experimental tumor metastasis was dose dependent and was observed when animals were treated the day before or the day after tumor-cell injection. Furthermore, repeated treatment of mice with this tilorone analogue significantly reduced lung colonization. PMID- 8509229 TI - Expression of L-PHA binding oligosaccharides and progression of mammary neoplasia are unrelated. PMID- 8509230 TI - The human melanoma antigen-encoding gene, MAGE-1, is expressed by other tumour cells of neuroectodermal origin such as glioblastomas and neuroblastomas. PMID- 8509231 TI - Clinical and pharmacological studies of interferon and chemotherapy in gastrointestinal and breast cancer. AB - The interferons enhance the cytotoxicity of antimetabolites, alkylating agents, and plant antibiotics against cultured human tumours in vitro and in vivo. Five clinical trials in humans with advanced colorectal carcinoma have demonstrated responses ranging from 26 to 63% in patients treated with 5-fluorouracil (5-FU) plus interferon-alpha (IFN-alpha), suggesting improved response with the combination as compared with 5-FU alone. In addition, responses have been observed in patients with adenocarcinomas of the lung, pancreas, breast, and kidney, squamous cell carcinoma of the oesophagus, and urothelial carcinoma treated with 5-FU/IFN-alpha. However, enhanced 5-FU-related toxicity was observed in these studies, as has been observed when 5-FU is combined with other modulating agents, such as leucovorin. While some studies suggested that enhanced 5-FU-related toxicity was associated with an IFN-alpha-induced reduction in 5-FU clearance when 5-FU was given as an intravenous (i.v.) bolus (750 mg/m2 IV weekly) or as a high-dose five-day continuous infusion (CI) (750 mg/m2/day x 5 days), another study found enhanced 5-FU toxicity in the absence of pharmacokinetic perturbation when 5-FU was given as a low-dose prolonged CI (300 mg/m2/day x 28 or more days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509233 TI - A randomized study of alfacalcidol in the refractory myelodysplastic anaemias. A Japanese cooperative study. AB - A multi-institutional randomized trial of alfacalcidol (1 alpha hydroxyvitamin D3) was performed to determine the therapeutic effect of alfacalcidol in patients with refractory myelodysplastic anaemias. Twenty-three evaluable patients were randomized to receive either a single daily oral dose of 6 micrograms of alfacalcidol or only supportive care as a control. Treatment was continued, whenever possible, for a period of 6 months. Response was assessed by weekly blood counts, clinical course and repeated marrow examinations. No significant difference was noted between the alfacalcidol and control groups. Three of the 13 patients in the alfacalcidol group, and two of the 10 patients in the control group, suffered a progression of their disease. One patient with refractory anaemia showed a good response to alfacalcidol in all three haematopoietic cell lineages; the response, however, could not be maintained, because discontinuation of the drug resulted in a worsening of pancytopenia which was refractory to a second course of alfacalcidol therapy. Hypercalcaemia was the major toxic side effect of alfacalcidol therapy. The results indicate that alfacalcidol therapy, when used alone, does not induce a beneficial effect in patients with refractory myelodysplastic anaemias. PMID- 8509232 TI - Pharmacokinetic and bacteriological study of cefadroxil-salicylate and josamycin salicylate drug regimens. AB - Eye, nose, throat and bronchopulmonary infections are frequently associated with inflammatory symptoms. This often leads the clinician to prescribe a combination of an anti-inflammatory and an antibiotic. Cefadroxil and josamycin are among the antibiotics most frequently used in these infections, and they are often combined with acetylsalicylic acid in various pharmaceutical formulations. The study of possible pharmacokinetic and bacteriological interactions was performed in healthy volunteers who received in a crossover protocol each of the two antibiotics, either alone or combined with acetylsalicylic acid or lysine acetylsalicylate. No marked pharmacokinetic interaction was noted except an increase in the AUC for plasma concentrations of cefadroxil when combined with a salicylate. A greater uniformity of kinetic profiles was seen with cefadroxil than with josamycin. Lastly, with the exception of one strain, the salicylates did not alter the antibacterial activity of cefadroxil. PMID- 8509234 TI - Pharmacokinetics and safety of single oral doses of amlodipine in patients with and without hepatic impairment: an open study. AB - An open study was conducted to assess the pharmacokinetics, cardiovascular effects and safety of a single oral dose of amlodipine 5 mg in 12 patients with hepatic impairment and eight healthy convalescing subjects. Cmax values were found to be similar in both groups although Tmax was shorter, and T1/2 was longer, in patients with hepatic insufficiency. AUCs were also higher in hepatic patients although these differences were not significantly different. No side effects or cardiovascular/ECG changes were observed in either group. Three patients with hepatic failure experienced mild laboratory abnormalities which were of doubtful clinical significance. PMID- 8509235 TI - Post-operative analgesia with tramadol: a controlled study compared with an analgesic combination. AB - The analgesic action of tramadol in the post-operative period was compared with that of an analgesic combination (Nisidin) in a sample of 60 patients (31 male, 29 female) aged between 20 and 70 years undergoing surgical operations on the abdomen involving opening of the peritoneum. The study was carried out according to a controlled and randomized experimental design. Tramadol in 100 mg/2 ml vials and Nisidin in 2 ml vials were administered parenterally at a dosage of three vials a day during the first three days of the post-operative period. The analgesic action of tramadol was shown to be more effective than that of Nisidin both after the first dose and during the three days of observation (p < 0.01). Local and general safety were good in both groups, and respiratory and heart rates did not undergo clinically significant modifications. In conclusion, tramadol proves to be particularly indicated in the treatment of post-operative pain, given that it has analgesic action combined with good local and general safety. PMID- 8509236 TI - Cisapride improves gallbladder kinetics in patients affected with myotonic muscular dystrophy. AB - Smooth muscle involvement is relatively common in myotonic muscular dystrophy (MMD). The effects of cisapride on gallbladder motor function in myotonic patients have been investigated in 10 alithiasic patients and in 10 healthy volunteers. Gallbladder volumes were measured by ultrasonography in fasting state and 15, 30, 45 and 60 min after milk intake. The patients were treated with cisapride for two months, after which they underwent a second ultrasonographic examination. Gallbladder emptying was slower and less effective in dystrophic patients than in healthy volunteers. Cisapride was found to improve gallbladder kinetics (efficacy of contraction and rate of emptying) in patients affected with myotonic muscular dystrophy. PMID- 8509237 TI - Salivary steroid changes and physical performance in highly trained cyclists. AB - The purpose of this work was to study the seasonal salivary cortisol and testosterone changes, and their relationships with lean body mass variations, in highly trained cyclists. Physical fitness, body composition (6 skinfolds) and basal salivary testosterone were evaluated in 7 male cyclists, on two separate occasions. The first assessment was made at the onset of the competitive season and the second 6 months later. Two kinds of exercise tests were carried out. The first test was an incremental exercise test to determine the maximum O2 consumption (VO2max) and the maximum workload (Wmax). We also measured the VO2 and workload (W) attained at the first and second ventilatory thresholds (VO2VT1, WVT1, VO2VT2, WVT2). During the tests the VO2 was recorded every 30 seconds (Oxycon-5, Mijhardt BV, Odijk). As a second test two days later, we assessed the anaerobic capacity expressed as the maximal accumulated O2 deficit (MAOD). Briefly, each subject underwent five submaximal exercises each lasting 6 min at an intensity of 200, 220, 240, 260 and 280 W. We estimated individually the O2 demand by extrapolating the linear relationship between the power and the O2 demand previously established. Afterwards the subjects performed a supramaximal bout at an intensity producing exhaustion between 2 and 4 minutes. The accumulated O2 demand was calculated by multiplying the O2 demand by the supramaximal test duration. The MAOD was computed as the difference between the accumulated O2 demand and the O2 consumed during the supramaximal rides. We found a significant increase in some physical fitness parameters related to aerobic capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509238 TI - Running capacity from adolescence to adulthood. Relationship to physical characteristics. AB - It has been shown earlier that the proportion of slow twitch (type I) fibres in the leg musculature is directly related to running performance in boys but not in girls at the age of 16. The purpose of the present study was to determine whether this pattern remains in adulthood. Forty-one men and 19 women were tested at the age of 16 and 27 years. Muscle biopsy specimens were obtained from the vastus lateralis and analysed for fibre type (I%, IIA%, IIB%). Maximal oxygen uptake (VO2max) was estimated from a submaximal exercise test. Running performance (9 min run) was assessed in a modified Cooper test. At age 16, the 9-min run was positively correlated with type I% and VO2max for the men. For the women, the 9 min run was positively correlated with VO2max but not with type I%. At age 27, the 9-min run was positively correlated with type I % and VO2max for both men and women. The appearance at the age of 27 of a relationship between running performance and type I% in the women could be related to the increase with age in the VO2max found in the women in the present study. These results support an earlier formulated hypothesis that a certain level of VO2max must be reached before peripheral factors such as the muscle fibre type composition are of any significance for the performance in a 9-min run. PMID- 8509239 TI - The effect of dynamic constant external resistance training on the isokinetic torque-velocity curve. AB - The purpose of this investigation was to examine the effects of dynamic constant external resistance (DCER) training on isokinetic peak torque (PT) and constant joint angle (CJA) torque at velocities from zero to 5.03 rad.s-1. Twelve male volunteers (mean age +/- SD = 21.67 +/- 2.61 years) were trained using DCER exercises (leg extension and squat) for eight weeks. The subjects were tested pre training and post-training for isokinetic leg extension PT as well as CJA torque (0.26 rad below the horizontal plane) at multiple velocities (zero, 0.84, 1.68, 2.51, 3.35, 4.19 and 5.03 rad.s-1) using a Cybex II isokinetic dynamometer. Film analyses indicated that the mean training velocities for leg extension and squat were 1.50 +/- 0.20 rad.s-1 and 1.41 +/- 0.26 rad.s-1, respectively. Univariate two-way repeated measures (within subjects design) ANOVAs [time (pre-training versus posttraining) x velocity] were used to analyze the changes in PT and CJA torque across the training period. There was no interaction but a significant (p < 0.05) main effect for time for the CJA torque measures. The increases in CJA torque ranged from 6.3 to 10.7%. For PT, there was a significant (p < 0.05) time x velocity interaction. Post-hoc comparisons showed that PT increased significantly at all velocities (p < 0.0083) as a result of the training (8.1 to 10.9%). The results of this investigation indicated that DCER training significantly increased isokinetic PT and CJA torque values at velocities up to 3.53 rad.s-1 above the training velocity. PMID- 8509240 TI - Aerobic requirement of bench stepping. AB - The purpose of this study was to: (1) verify the aerobic requirement (AR) of bench stepping (BS); (2) determine the effect of leg length (LL), bench height (BH), stepping rate (SR), body weight (BW), and fat free mass (FFM) on the AR of BS; and (3) compare the HR and VO2 of BS with treadmill walking/running (TM). Twenty-eight females completed randomly assigned BS sessions with hands on hips at 30 and 32 step cycles.min-1. Sessions consisted of four 5 min. bouts at BH of 15.2, 30.4, 25.4 and 30.5 cm. A 4 x 2 repeated measures ANOVA determined that VO2 was significantly different between each BH and SR (p < 0.01) with no significant interaction between BH and SR (p > 0.05). A stepwise multiple regression determined that BH, BW, SR, FFM, and LL significantly affected BS VO2 (p < 0.05) with BH and BW accounting for 83% of the VO2. A series of t-tests found no significant difference (p > 0.05) between measured VO2 and that predicted by the ACSM equation (1) at 15.2, 20.3 and 25.4 cm. Measured VO2 was significantly greater than predicted at 30.5 cm (p < 0.01). A repeated measures ANCOVA determined that the VO2/HR slopes for BS and TM were not parallel (p < 0.01). Point testing determined that the HR elicited by TM at a specific VO2 was significantly higher than the BS HR until 34 ml.kg-1 x min-1, but the SEE revealed large overlapping of HR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509241 TI - Individual anaerobic threshold and maximum lactate steady state. AB - The individual anaerobic threshold (IAT) as defined by Stegmann et al. 1981 is determined by using the blood lactate-performance relationship during incremental graded exercise and the immediately following recovery phase. The aim of the study was to investigate the validity of the IAT as a measure for the maximum lactate steady state (max Lass) and the monitoring of endurance training. Sixteen endurance trained athletes (VO2max 60.2 +/- 5.0 ml.min-1 x kg-1) performed a stepwise increasing test until exhaustion on a cycle ergometer (CE) (increasing by 50 W every 3 min), 14 endurance trained athletes (VO2max 64.9 +/- 3.8 ml.min-1 x kg-1) performed the multistage steptest on a treadmill (TM) (increasing by 0.5 m.s-1 every 3 min) to determine the IAT and the 4 mmol.l-1 La-threshold (AT). Afterwards endurance tests (E) limited to 30 min (CE) or 45 min (TM) were performed with intensities of 85, 95, 100 and 105% of the IAT (E85-E105) and with 100% of the AT (AT100) (only on CE) in a randomized order each on different days. Lass was present without premature break-off during E85 (in 30 out of 30 cases), E95 (30/30 cases) and E100 (26/30 cases). At E105 and AT100 (104 +/- 7% of IAT) mean La increased continuously and/or led to a premature break-off (in 15/30 cases). All subjects with an AT below their IAT were in Lass during AT100.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509242 TI - Orthotic devices in functional treatment of ankle sprain. Stabilizing effects during real movements. AB - Various orthotic devices generally employed for therapy of ankle sprain were tested under functional conditions. The experimental setup comprised inversion stimuli of 20 and 30 degrees (13 subjects) while standing on a tiltplatform as well as running movements of 8 and 12 km.h-1 on a treadmill (12 subjects). Ankle joint displacements were registered together with the surface EMGs from mm. peroneus long., tibialis ant., gastrocnemius med. and vastus med. In an additional study the relation between achilles tendon angle and talar tilt was determined under static conditions. Ten subjects with chronical instability were examined both in uni- and bipedal stance with the foot inverted to 20, 30 and 40 degrees. None of the tested devices could reduce achilles tendon angle movements completely neither during a sudden inversion nor during running. However, there were significant differences among the tested devices in the dorsal-plantar and in the eversion-inversion plane. In bipedal stance talar tilts were observed only when the foot was inverted more than 30 degrees. In unipedal stance these tilts were clearly reduced or disappeared totally. It is concluded that for functional rehabilitation, loading of the ankle joint is desirable in order to increase joint stability. The central importance of the treatment by orthotic devices may be regarded in an optimal passive joint stabilization combined with a correct fitting in order to preserve proprioceptive neuromuscular function for an active muscular stabilization. PMID- 8509243 TI - Knee laxity and function after conservative treatment of anterior cruciate ligament injuries. A prospective study. AB - Knee laxity and function were investigated in a prospective study including 40 patients with acute anterior cruciate ligament injury and 11 patients with minor knee injury not involving the cruciate ligaments (controls). None of the patients had primary ligament repair. Instrumental testing (OSI, Hayward, California) of the static laxity of both knees was performed at one, three, six, and 12 months after the injury. The initial laxity of the anterior cruciate-deficient knees was greater than that of the controls. At 12 months the laxity at 180N tibial load for the patients with anterior cruciate ligament injury exceeded the laxity found within one month of injury. At 12 months half of these patients complained of symptoms of instability and one out of four patients had had severe subluxations with accompanying haemarthrosis. Patients with combined anterior cruciate and medial collateral ligament injury had the greatest initial laxity and the worst outcome. In all, 20% of the patients were scheduled for reconstruction of the anterior cruciate ligament during the observation period. PMID- 8509245 TI - Idiopathic progressive sensorineural hearing loss in children. AB - Clinical observations were made of 42 children with bilateral idiopathic progressive sensorineural hearing loss considering hearing loss distribution in relation to age at onset, audiometric features, audiologic characteristics and possible correlation with some haematochemical alterations. Patients were divided into 2 groups on the basis of hearing onset: Group I, 0-6 years; Group II, 7-14 years. A peak in the distribution of onset age was observed in the range of 4-6 years. In most cases a 'descending' curve was recognized accompanied by recruitment. The haematochemical tests only suggested a possible correlation between hearing loss and anaemia. Finally, no significant difference of incidence between the sexes was observed. PMID- 8509244 TI - The optimization of hearing-impaired children's speechreading. AB - As more hearing-impaired and deaf children are mainstreamed into regular schools and as age related hearing loss in advanced countries become more prevalent, so the need for optimal methods to teach speechreading increases. The numbers of children and adults who would benefit from improved methods of teaching speechreading must be considerable. No new methods of teaching speechreading have been developed since 1938. Speechreading is a skill that does not require complex technology, although it does augment the effectiveness of hearing aids. Increased knowledge of this skill would have great benefits in psychological, social and economic terms. Some relevant experimental psychological literature and the views of educators are discussed with the goal of contributing to the optimization of hearing-impaired children's speechreading. PMID- 8509246 TI - Habitual snoring and obstructive sleep apnea syndrome in children: effects of early tonsil surgery. AB - Habitual snoring and obstructive sleep apnea syndrome (OSA) in children are important in determining disturbed sleep, daytime symptoms and haemodynamic modifications. Moreover, chronic snoring is often associated with enlarged tonsils and adenoids. We studied 60 children (mean age 42.2 months) with habitual snoring, defined as a positive answer to the question 'does the child snore every night', by nocturnal or diurnal polysomnography in order to evaluate breathing disorders and choose surgical correction of upper airway stenosis. In more than half the children habitual (every night) snoring begin before the first year of life and is associated with obstructive apneas. Both nocturnal and, with some limits, diurnal recordings may be a good tool for diagnosis of sleep-related upper airway obstruction. Early adenomonotonsillectomy, in mild to moderate form and in children before 4 years of age, and adenotonsillectomy in the others seems to show a clinical and polysomnographic resolution of snoring and OSA during a short-term follow up. PMID- 8509247 TI - Effects of sulfur dioxide and smoke on the incidence of laryngotracheitis (croup). AB - During the 1981-1990 period, 652 children, 70% boys and 30% girls, were hospitalized at the Zagreb University ENT Department for laryngotracheitis (croup). Most of the children were hospitalized at the age of 2, and 90% of all children were under the age of 7. The highest number of cases of laryngotracheitis were admitted during autumn, especially in October, and the lowest in July. No correlation was found between the mean and peak monthly values of sulfur dioxide and smoke in the air in Zagreb and the number of children hospitalized for laryngotracheitis. PMID- 8509248 TI - Use of acetic acid to delineate laryngeal papilloma better. AB - Topical application of acetic acid into larynx of a child with papilloma is shown to delineate pathology better. PMID- 8509249 TI - Tracheobronchomalacia in Hunter's syndrome. AB - Hunter's syndrome is one of a group of heritable metabolic disorders caused by decreased activity of one or more of the lysosomal enzymes responsible for mucopolysaccharide catabolism, resulting in excessive deposition of mucopolysaccharides in skeletal and soft tissues. Pulmonary conditions, such as airway obstruction, sleep apnea syndrome, atalectasis, recurrent pneumonia and difficult endotracheal intubation are known to be associated with these rare disorders and have been reported. We report the findings at laryngotracheobronchoscopy of a patient with Hunter's syndrome with airway symptoms and, supported by analysis of previously reported cases of airway problems associated with the syndrome, suggest that tracheobronchomalacia with classifiable major airway collapse (MAC) may be the pathological correlate for this clinical picture. The endoscopic technique and characteristic findings of tracheobronchomalacia/MAC are discussed, as well as the natural history and pathophysiology of this condition, which is characterized by weakness of the tracheal wall due to softening of the supporting cartilage and hypotonia of the myoelastic elements with reduction in the tracheal lumen. PMID- 8509250 TI - Transitory evoked otoacoustic emission (TEOAE) in a child with profound hearing loss. AB - The case of a 3-month-old, prematurely born boy with auditory brainstem response (ABR), verified profound hearing loss and normal transitory evoked otoacoustic emission is presented. Isolated retrocochlear deafness which did not influence TEOAE is hypothesised as a possible cause. The critical evaluation of results when using TEOAE as a screening method is suggested. PMID- 8509251 TI - [Identifying the patient with unstable heart rhythm]. PMID- 8509252 TI - [The status of new procedures for improving the diagnosis of ventricular tachycardic arrhythmias. Frequency variability, late potentials, signal transmission]. PMID- 8509253 TI - [Prevention of sudden (rhythm-induced) cardiac death]. PMID- 8509254 TI - [Anti-arrhythmic therapy of ventricular arrhythmias. Assessing benefit and risk]. PMID- 8509255 TI - [Non-medicamentous therapy of tachycardic cardiac arrhythmias]. PMID- 8509256 TI - [Chylous lung and chyloptysis in mediastinal lymphangioma]. PMID- 8509257 TI - [Insulin resistance in secondary diabetes mellitus]. PMID- 8509258 TI - [What is the ophthalmologic recommendation for managing diabetes with reference to diabetic retinopathy]. PMID- 8509259 TI - [Therapy of atrial fibrillation]. PMID- 8509260 TI - Don't ingest it, don't touch it, don't breath. PMID- 8509261 TI - Clinton staff is listening, but health care reform plan remains a mystery, says AMA trustee. PMID- 8509262 TI - Poll reflects sick society. PMID- 8509263 TI - Policy regarding HIV-infected health care workers. PMID- 8509264 TI - Massasauga rattlesnake bites in Iowa. AB - Historically, bites from swamp rattlesnakes in Iowa have been mild, but a bite in eastern Iowa in 1990 produced life threatening thrombocytopenia. Only four populations of massasauga rattlesnakes have been verified in Iowa. PMID- 8509265 TI - Where has all the money gone? PMID- 8509266 TI - Be a critical reader. PMID- 8509267 TI - Short term prognosis of stroke in a clinical series of 94 patients. AB - We conducted a study on the factors predictive of early mortality (within 30 days of onset of symptoms) in a clinical series of 94 patients at their first stroke. Irrespective of the type of stroke, ischemic or hemorrhagic, early mortality proved to correlate with clinical parameters, such as coma at onset, presence of paralysis, changes in ocular motility, and neuroradiological parameters (lesion size on the CT scan) indicative of stroke severity. PMID- 8509268 TI - Antiphospholipid antibodies syndrome and cerebral ischemia. AB - Antiphospholipid antibodies are acquired circulating immunoglobulins that interact with phospholipids. These factors may manifest anticoagulant properties in vitro, interfering with phospholipid-dependent coagulation tests. They are not, however, associated with a hemorrhagic diathesis. Indeed, far from exerting the anticoagulant properties they possess in vitro, they are associated with episodes of thromboembolism, systemic and cerebral. We report the clinical and instrumental findings in 7 patients with ischemic stroke and circulating antiphospholipid antibodies classifiable as antiphospholipid antibodies syndrome. PMID- 8509269 TI - Hyperekplexia and stiff-baby syndrome: an identical neurological disorder? AB - Hyperekplexia (startle disease) is an unusual, familial, neurological disorder characterized by abnormally enhanced startle response, followed in most cases by momentary generalized muscular stiffness. These attacks may cause the patients to fall rigidly, while remaining fully conscious. Startle symptomatology has generally an onset in infancy and is often accompanied, during the first years of life, by rigidity, sleep myoclonus, motor delay, regurgitation and apneic spells, which may cause sudden death. Stiff-baby syndrome is a familial disorder characterized by marked rigidity, with neonatal onset and gradual reduction during infancy, regurgitations, motor delay and attacks of stiffness. We report 4 new cases of hyperekplexia from two different families and another infant with stiff-baby syndrome discussing clinical, electrophysiological and genetic aspects of both neurological disorders in relation to other reported cases. We suggest a continuum between these familial syndromes, which are often misinterpreted as epilepsy or other disorders. PMID- 8509271 TI - Dopamine D2 receptor imaging with SPECT using IBZM in 16 patients with Parkinson disease. AB - The striatal D2 receptor was investigated for variability of behavior in 16 patients with Parkinson disease by means of SPECT using 123I-IBZM, a recently synthesized radioligand with high affinity and specificity for this type of receptor. All the patients underwent routine laboratory tests, EEG and cranial CT scanning as well as SPECT. To ensure accurate clinical assessment we used the Hoehn and Yahr, and Webster scales, NUDS and Mini Mental State examination. Our preliminary data indicate: increased uptake by the striatal dopamine receptor in untreated patients with early PD compared with controls (striatum/cerebellum ratio of 1.77 +/- 0.12 vs 1.59 +/- 0.13); a slight but significant lowering of D2 receptor binding when L-Dopa is started (1.49 +/- 0.09); low D2 uptake values in the more severely affected patients; absence of asymmetries in hemiparkinsonism. PMID- 8509270 TI - Monocyte chemotactic and phagocytic responses in migraine and tension-type headache patients. AB - Monocyte chemotactic and phagocytic responses were assessed in two groups of migraine patients (with and without aura) and in two groups of tension-type headache patients (episodic and chronic). The chemotactic but not the phagocytic response, assessed interictally, is significantly lower in migraine patients (p < 0.006) and in episodic tension-type headache patients, though not so significantly in the latter (p < 0.05), than in the control individuals. The chemotactic response tends to increase significantly during attack in migraine patients both with and without aura (p < 0.008 and p < 0.007 respectively). The same was evident for the phagocytic response in both migraine patient groups (p < 0.007 and 0.0004). No modifications of monocyte functions were found during attacks neither in episodic nor chronic tension-type headache patients. These findings suggest that one or more mediators of neurogenic inflammation having phagocytic and chemotactic enhancing properties (substance P, prostaglandin E and thromboxane A2 etc.) are implicated in the modification of monocyte function. The demonstration of a defect in monocyte function during the interictal period in migraine patients confirms the results of recent research which evidenced reduced capacity of monocyte to phagocyte and kill microorganisms in the course of migraine. PMID- 8509272 TI - Predictive value of neurological abnormalities in HIV 1 patients in the early stages of the infection. AB - A longitudinal clinical neurological and electrophysiological follow-up study was carried out on 31 HIV1 seropositive outpatients in the asymptomatic or LAS stages of the infection (CDC II-III). The results of clinical examination and multimodal evoked potentials (EP) recording showed a high percentage of abnormalities (42% and 39% of cases respectively); in a statistically significant number of subjects these abnormalities were predictive of subsequent immunological deterioration, thus demonstrating the close relationship between neurological and immunological functions in HIV1 infection. PMID- 8509273 TI - The care of epileptics: from the madhouse to the League against Epilepsy. AB - We trace the first steps in the organization of the International League against Epilepsy, the great initial impetus for which came from an Italian savant, Prof. Tamburini, among others. The League came into being because of the need to differentiate epilepsy from insanity and to channel into a single institution all research into the etiopathogenesis, new therapies and principles of care to ensure their rapid diffusion all over the world. PMID- 8509274 TI - Chronic or long-term psychiatric patients: potential subjects for longitudinal research. AB - The frequently admitted "revolving door" chronic psychiatric patient presents significant ethical, scientific, and practical challenges to mental health nurses. This article highlights ethical issues relevant to their participation in longitudinal research and describes methods implemented to successfully follow a cohort of such patients over a 2-year period. PMID- 8509276 TI - Hope in older adults in community and institutional settings. AB - This study explored the meaning of hope, the influence of specific background characteristics on hope, and identified strategies that are used to foster hope in a convenience sample of 60 older adults using the technique of methodological triangulation (interview, Hope Index, and Background Data Form). Hope was described as an expectation of a brighter tomorrow for self and/or others. Perceptions of hope were found to be influenced by place of residence, age, energy level, functional ability, and health status. With the exception of those participants experiencing severe fatigue and those residing in a long-term care facility, overall hope levels among subjects were high and were found to remain stable across the background variables. Eight hope-fostering categories and four hope-hindering categories were identified based on the interview responses. Implications for practice and research are presented. PMID- 8509275 TI - Qualitative study of women's reports of family adaptation pattern four years following transition to parenthood. AB - This prospective qualitative study examined patterns of family adaptation over 4 years following the birth of a first child. Data were collected on 16 first-time mothers during their second trimester of pregnancy, at 4 months, 1 year, and 4 years after the birth of the infant. Both standard measures and an intensive semistructured interview were used to assess change in women's perceptions of marital adaptation and role reorganization. Using a case-study method, data were analyzed for patterns of family adaptation. Interview data showed that marital distress and later family disorganization patterns were related, in part, to the changes in the marital system starting during the early transition to parenthood, suggesting that subjects' negative perceptions of marital satisfaction as early as 4 months postbirth forecasted later family adjustment problems. Socioeconomic stress and substance use was associated with the changes for some of these subjects. Alternative interpretations and future directions for study are discussed. PMID- 8509277 TI - Elderly relocation to a congregate setting: factors influencing adjustment. AB - As the trend in relocation to congregate housing continues, protecting the well being of relocating elderly becomes a major concern. The relationships of perceived choice, predictability, perceived social support, cognitive appraisal, and coping strategies on relocation adjustment were examined through semistructured interviews with elders relocating to a congregate setting in New York state. Perceived choice in relocation, predictability, perceived social support from family and neighbors, and cognitive appraisal of the move as threat or challenge were found to correlate significantly with adjustment. The majority of subjects viewed the move to a congregate setting positively, predominantly as a challenge, and as different but not extremely difficult. This study provides increased research-based understanding of the factors influencing postrelocation adjustment and fuller understanding of the personal meaning of the relocation experience that may be used to aid the successful transition of an older person to a group residential setting. PMID- 8509278 TI - Posttraumatic stress in battered women: does the diagnosis fit? AB - Posttraumatic stress disorder (PTSD) has been recommended as an appropriate psychiatric diagnosis for battered women. The criteria for the diagnosis are reviewed along with research that supports its application in battering situations. Definitional, diagnostic, research, and treatment issues using the diagnosis with abused women also are discussed, including recommendations for future investigations and clinical application. PMID- 8509279 TI - Effects on children of having lived with a parent who has an anxiety disorder. AB - The purpose of this article is to show that the mental illness of a parent, in this case an anxiety disorder, can have a significant, negative impact on children. A brief history of the concept of anxiety is provided, showing the multifaceted nature of anxiety. The Integrative Model of Anxiety (Akiskal, 1985) is outlined to provide a current definition of anxiety. This article concludes by describing the role that nursing can play in intervening on behalf of children whose parents have an anxiety disorder. Finally, a proposed study is outlined. PMID- 8509281 TI - Social support as experienced by Roman Catholic priests: the influence of vocationally imposed network restrictions. AB - This qualitative descriptive study explored the experience of social support as perceived by four Roman Catholic priests who are community caregivers subject to role-related stressors and who have vocational limitations placed on their social support networks. The data collection process consisted of two semistructured interviews employing open-ended questions. Content and concept analysis techniques yielded seven core themes (person-role disharmony, intimate connections, network leveling, moving networks, caregiver survival, vocation person esteem, caring relationships), three prevailing themes (subsistent relationships, person-priest being, reciprocal fulfillment), and one contextual theme (presence). The priests actively sought support as a means of coping with the daily stress associated with their caregiving roles. Large and diffuse networks were unable to compensate for restrictions resulting from vows of celibacy, discord accompanying midlife transition, or conflicts associated with socially prescribed role expectations of the priesthood. The instability of their support networks resulting from mandatory transfers may have been a contributing factor. Existential presence, an enduring theme, was identified as an inherent quality of caregiving and social support. PMID- 8509280 TI - Self-perceptions of interpersonal and sexual functioning in women with mood disorders: a preliminary report. AB - Women with mood disorders are faced with the complex interpersonal issues that confront all women, as well as the potential disruption in their interpersonal functioning related to the nature of their disorder and the medical treatment required. The purposes of this study were to describe the self-perceptions of 34 women being treated medically for mood disorders regarding (a) their interpersonal and sexual functioning, (b) the causal explanations for perceived disruptions in interpersonal and sexual functioning, and (c) the effect their mood disorder has had on their functioning in these areas. A structured questionnaire was used to conduct the in-depth interviews. Results indicated that 76.5% (n = 26) of the women perceived that they were experiencing interpersonal disruption, and 55.9% (n = 19) perceived that they were experiencing sexual disruption at the time of the interviews. Moreover, 88.2% (n = 30) reported that their mood disorder had an effect on their interpersonal relationships, and 79.4% (n = 27) reported that their mood disorder adversely affected their sexual relationships. Causal explanations related to the perceived disruptions in functioning were explored. PMID- 8509282 TI - A psychiatric overview of cult-related phenomena. PMID- 8509283 TI - A well-deserved Sabbath rest: three Freud patriarchs. PMID- 8509284 TI - Clinical issues for pregnant psychoanalysts. PMID- 8509285 TI - "Breaking the law," a metaphor for female empowerment through aggression: women in film. PMID- 8509286 TI - The relationship between formal operations cognition and suitability for psychoanalytic treatment. AB - Psychoanalytic practice can benefit from a coherent theory of cognition that is more comprehensive than, but which includes the related concepts of primary/secondary processes. For reasons not yet understood, cognition has not received the continuing attention it deserves in psychoanalytic theory. As demonstrated, Piaget's empirical studies of cognition can potentially help the practicing psychoanalyst to clinically differentiate those patients suitable for psychoanalytic treatment. It appears that Piaget's theory may hold greater utility for psychoanalysis than has been evidenced to date and analysts may be able to eventually describe defensive operations as well as other ego functions in terms of the cognitive functions delineated by Piaget. PMID- 8509287 TI - The darker forces: Freud and the movies. PMID- 8509288 TI - Idealization and its discontents: a reconsideration of the functions and limits of a psychic phenomenon. AB - This study defines and illustrates the connections and differences between an idealizing and capacitating relationship. We first identified the patient's requirements for an idealized object, both to facilitate the reinforcement of a circumscribed but positive sense of herself, and to ward off dysphoric affect states in the domains of core- and intersubjective relatedness. These requirements were then distinguished from her need at a deeper level (the true self) to find a capacitating object to affirm, tolerate, and contain the full range of affects in her lived experience with others. These two sets of requirements have a different feel in the transference; and countertransference responses may be a valuable means of recognizing and distinguishing each as elements of different structures of self-organization. PMID- 8509289 TI - Freud's analysis of A.B., a psychotic man, 1925-1930. PMID- 8509290 TI - Adaptation to the dominant society and identification with the aggressor as factors in the treatment of Chicanos. PMID- 8509291 TI - The addictive process: a psychoanalytic understanding. PMID- 8509292 TI - Cell and matrix changes associated with pathological calcification of the human rotator cuff tendons. AB - The causative mechanism of tendon calcification ('calcifying tendinitis') is unknown. In this report, pathological human tendon samples were examined to give morphological and ultrastructural detail of the calcified regions and these findings were compared with those from normal tendon. Selected specimens were cryosectioned to enable histochemical and immunohistochemical comparison of the occurrence and distribution of specific matrix molecules in diseased and normal tendon tissues. The lack of collagen type II and alkaline phosphatase in the pathological regions suggests that the calcification process is not mediated through an endochondral transition. In contrast, the pathological areas were characterised by widespread labelling for chondroitin-4-sulphate/dermatan sulphate and intense pericellular localisation of chondroitin-6-sulphate. PMID- 8509293 TI - High incidence of the third head of biceps brachii in South African populations. AB - Three different origins were found for the third head of the biceps brachii: (1) an origin from the humeral shaft inferior to and in common with the insertion area for the coracobrachialis; (2) a brachial origin in which the muscle originated distally from the medial humeral shaft, adjacent to and in common with the brachialis muscle; (3) a dual origin in which the medial fibres originated from the short head of biceps and the lateral fibres from the deltoid fascia and the insertion area of this muscle. In all cases, the third head inserted together with the other 2 heads of biceps brachii into the bicipital aponeurosis and the radial tuberosity. The third head receives its innervation from the musculocutaneous nerve, as do the other 2 heads of biceps. When there is a dual origin, partial innervation from the axillary nerve is possible since the fibres of the third head intermingle with those of the deltoid. There was a 20.5% incidence of the third head in South African blacks and only an 8.3% incidence in South African whites. Statistical analysis showed the difference between South African whites and blacks to be significant (P < 0.05). Not all of the blacks, however, had a higher incidence, since the Zulus showed a significant absence (P < 0.05) of the third head when compared with the other black populations. PMID- 8509294 TI - An accessory extensor digiti minimi arising from extensor carpi ulnaris. AB - In a study of an accessory extensor digiti minimi arising from extensor carpi ulnaris in 240 upper limbs, an accessory tendinous slip originating from extensor carpi ulnaris was observed in the tunnel of the 6th compartment at the wrist in 82 (34.2%). The slip inserted into one of several sites on the 5th metacarpal bone, such as on the base with the main tendon (29.6%), on the midportion (2.5%) or on the head (1.7%). The last type of accessory tendinous slip, which was connected with the extensor aponeurosis of the little finger, is the accessory extensor digiti minimi arising from extensor carpi ulnaris described by Kaplan & Spinner (1984). PMID- 8509295 TI - Bruch's membrane with an elastic lamina in the eye of a teleost. AB - This paper reports the existence of an elastic lamina in Bruch's membrane in the eye of the teleost Notopterus notopterus. It is considered that the exceptional thickness of Bruch's membrane provides support for the tall and expanded retinal pigment epithelial cells characteristic of this species. The functional significance of the elastic layer is not understood. PMID- 8509296 TI - New structural aspects of the synaptic contacts on Purkinje cells in an elasmobranch cerebellum. AB - Nerve fibre contacts on Purkinje cell perikarya in the cerebellum of the small spotted dogfish (Scyliorhinus canicula) were studied using the Cajal reduced silver technique, Golgi methods and electron microscopy. Silver staining revealed axons with thick swellings close to the base of Purkinje cells. Golgi methods demonstrated the presence of 'pincushions' of somatic spines on Purkinje cells. Electron microscopy revealed flattened fibres that formed extensive synaptic contacts with the Purkinje cell 'pincushions'. It is proposed, on the basis of the ultrastructural features, that these fibres are climbing fibres. Their possible significance in terms of the evolution of cerebellar circuitry is discussed. PMID- 8509297 TI - Distribution of pacinian corpuscles in the cat forefoot. AB - The distribution of pacinian corpuscles in the cat forefoot was investigated using celloidin sections stained with haematoxylin and eosin. The corpuscles were oval or elliptical, their longitudinal and transverse diameters being 590.0 +/- 207.6 microns and 320.0 +/- 119.6 microns. There were 667 corpuscles (mean value for 4 feet) in each forefoot, 80% of which were in the toe region and the remainder in the palmar region. The number of corpuscles was similar in both forefeet. There was no difference in light microscopic structure. Corpuscles were located (1) in the dermis and subcutaneous tissue of the skin folds covering the claw, (2) between the flexor digitorum tendon and middle phalanx, (3) in the subcutaneous adipose tissue of the metacarpal pad and (4) in short digital muscle of the carpal pad. Scattered corpuscles were found in contact with the periosteum of distal and middle phalanges and with flexor tendon sheath, and in the dermis of the palm. Corpuscles were observed to be clustered in the skin folds of the toes. Skin folds, made of dorsal hairy skin, covered the claw on both sides, with most corpuscles in contact with hair follicles and others scattered between hair follicles. Forefoot corpuscles were often in proximity with blood vessels. Corpuscles in the palmar region were seen to be arranged along the superficial palmar metacarpal nerve. PMID- 8509298 TI - The effect of nutrition on the size and proportion of muscle fibre types during growth. AB - To investigate whether the retardation in the increase of body weight produced by reduced food intake could influence the transformation of muscle fibre types in soleus and extensor digitorum longus (EDL) during growth, rats were divided into 3 groups at 3 wk of age. Each group was subjected to food restriction from 3 wk of age to the following ages. Group 1 comprised 5 (148.7 +/- 7.3 g), 7 (250.7 +/- 11.1 g), 9 (362.9 +/- 19.3 g) and 11-wk-old rats (414.9 +/- 35.2 g) fed ad libitum. Group 2 comprised 5 (148.7 +/- 7.3 g), 7 (148.6 +/- 7.7 g), 9 (147.7 +/- 6.0 g) and 11-wk-old rats (148.8 +/- 5.7 g) fed a restricted diet; these animals were similar in weight to the 5-wk-old rats in group 1. Group 3 comprised 4 subgroups of 11-wk-old rats (148.7 +/- 5.7 g, 247.6 +/- 6.8 g, 354.4 +/- 8.6 g, 414.4 +/- 35.2 g); their body weights were adjusted to the weights of 5, 7, 9 and 11-wk-old rats in group 1 by restriction of food intake. Muscle weights and fibre areas in soleus and EDL significantly increased with growth. The muscle weights and fibre areas in group 2 in which body weights were equal increased significantly with age, but the increases were significantly less than for group 1. The muscle weights and fibre areas in group 3 in which ages were equal increased significantly with increasing body weight; the increases were the same as those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509299 TI - Microcirculation of the extrahepatic biliary tree: a scanning electron microscopy study of corrosion casts. AB - The microvascular arrangement of the extrahepatic biliary tree of the rat was studied by light microscopy (LM) and scanning electron microscopy (SEM) of vascular corrosion casts. The plexus that encircles the lumen of the common bile duct, observed by LM, showed a network of vessels of different diameter situated under the epithelium in the lamina propria. Parallel SEM observations of the same structure demonstrated the presence of 2 main vascular layers: an outer arterial and venous layer, corresponding to the larger vessels seen by LM, and a richer inner capillary layer just under the epithelium. On the luminal part of the corrosion casts, there were many round avascular empty pits that corresponded to the presence of small acinar glands distributed along the epithelium of the common bile duct. The rich subepithelial capillary network present in the rat, an animal without a gallbladder, may play an important role in the reabsorption of water and solutes from bile. Moreover, in pathological conditions (e.g. portal hypertension), liver blood flow may take a preferential collateral route through the intrahepatic peribiliary plexus into the relatively large diameter vessels of the extrahepatic peribiliary plexus because of the continuity of the 2 plexi. PMID- 8509300 TI - Variation with age in the labelling of amoeboid microglial cells in rats following intraperitoneal or intravenous injection of a fluorescent dye. AB - Amoeboid microglial cells (AMC) in the corpus callosum were selectively labelled following a single intraperitoneal (i.p.) injection of the fluorescent dye, rhodamine isothiocyanate (RhIc) into postnatal rats. The frequency of RhIc labelled cells varied with age, with the largest number occurring in 7-d-old animals. Thereafter, the labelled cells declined drastically in number and fluorescence and were barely detectable in 12-d-old injected rats. Labelled cells were absent in 13-d or older rats given an RhIc injection. When the injected RhIc was followed over a time course sequence, it was first detected in the cerebral blood vessels and their lining endothelia within 5 min after the injection. A variable number of AMC emitting a weaker fluorescence were closely adherent to the outer walls of the blood vessels. With time, the fluorescence in the AMC was progressively enhanced, but that in the blood vessels showed a concomitant reduction. In the rats that received an intravenous (i.v.) injection of RhIc, the labelling pattern of AMC, both in terms of its variation with age and in temporal sequence, paralleled that in rats given i.p. injections. In 12-d-old rats subjected to a stab wound coupled with an i.p. injection of RhIc, a considerable number of AMC not normally labelled at this age were activated. The cells exhibited an intense fluorescence and expressed MHC surface antigen immunoreactivity. It is concluded from this study that when injected i.p. or i.v., RhIc is readily circulated to the cerebral vessels, where it enters brain tissue by transendothelial transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509301 TI - The inheritance of vertebral shape in the mouse. II. A study using Fourier analysis to examine the inheritance of patterns of vertebral variation in the cervical and upper thoracic vertebral column. AB - In this paper we continue an earlier study which examined shape differences between the cervical and upper thoracic vertebrae of 2 inbred strains of mice (CBA, C57BL) and their F1. Our earlier study showed that the amount of shape difference varied between different vertebrae, even from adjacent levels, and that the vertebrae of the F1s showed a degree of resemblance to one or other parental strain which varied from vertebral level to vertebral level. We have suggested that this variation from level to level may have evolutionary significance in that it demonstrates a degree of autonomy in the genetic control of vertebral morphology between successive levels and, as such, allows the possibility of a form of mosaic evolution. In this study we further consider the inheritance of vertebral morphology both in the above-mentioned and in other crosses: this time, however, we focus on the ways in which vertebral morphology changes from level to level and on any differences in patterns of metameric change between inbred strains and their offspring. Our findings indicate that the morphology of vertebrae shows a metameric gradation in shape and that the rates of shape change along the column can vary from region to region. Furthermore, the F1 between 2 inbred strains may follow the pattern of variation characteristic of one parent for several metameric segments at a time. Different crosses between different inbred strains indicate that many genes influence the pattern of metameric variation in the vertebral column and that these genes have different actions along the column.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509302 TI - Uterine morphology and the distribution of granulated metrial gland cells in the virgin and pregnant short-tailed field vole, Microtus agrestis. AB - The morphology of the uterine wall in the virgin pregnant and postpartum short tailed field vole (Microtus agrestis) was studied with particular reference to the distribution of granulated metrial gland (GMG) cells. In comparison with the mouse, the changes which occur in the uterine wall during pregnancy and into the postpartum period are broadly similar. However, unlike in the mouse, GMG cells were a feature of the uterine wall in virgin mice and of the antimesometrial decidua in pregnancy. In pregnancy, GMG cells were not found in the lumina of blood vessels in the uterine wall or in the maternal blood spaces of the fetal placenta. During early pregnancy, giant interstitial trophoblast cells invade the decidualising endometrium. No association was found between uterine leucocytes, including GMG cells, and interstitial trophoblast cells, indicating that the trophoblast invasion is not influenced by leucocytes. PMID- 8509303 TI - The atrioventricular valves of the mouse. I. A scanning electron microscope study. AB - This paper reports a scanning electron microscope study of the morphology of the atrioventricular (AV) valves in the mouse. The leaflet tissue of the 2 AV valves consists of a continuous veil that shows no commissures or clefts. In all instances, the chordae that arise from the papillary system merge with the free border of the leaflet tissue. No distinct terminations of chordae were observed on the ventricular face of the valves. The leaflet tissue of the right AV valve can be divided into parietal and septal components on the basis of the insertion into the ventricular wall and of the papillary system. While the septal component is similar in shape, location and tension apparatus to the septal tricuspid leaflet in man, the parietal component appears to correspond to the anterior and posterior human leaflets. This segment of the valve is served by 3 papillary muscles that arise from the septal wall. The right AV valve is not a tricuspid structure from the morphological standpoint, but appears to function as such because of the particular attachment of the papillary muscles. The leaflet tissue of the mitral valve is served by 2 papillary muscles, anterior and posterior, which consist of muscular trabeculae extending from the heart apex to the base of the valve. These muscles remain associated with the ventricular wall. The leaflet tissue attaches directly to these papillary muscles, which give rise to a very small number of slender chordae. There are thus several important differences between the AV valves of the mouse and man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509304 TI - Immunocytochemical localisation of insulin receptors on rat superior cervical ganglion neurons in dissociated cell culture. AB - Cells in dissociated culture preparations of the superior cervical ganglion of the adult rat were examined for the presence of insulin receptors. This was assessed immunocytochemically by the demonstration of binding by a mouse monoclonal anti-insulin receptor antibody. A large subpopulation (> or = 90%) of neuronal cell bodies and associated neurites exhibited positive immunostaining. The apparent absence of staining over nuclear regions suggested that the majority of neuronal receptors had an intracytoplasmic localisation. In contrast, a subpopulation of fibroblasts showed punctate immunostaining, which appeared to be confined to the cell surface. Glial (satellite) cells did not appear to be immunostained. The possible effects of insulin on neurons in the peripheral nervous system are discussed. PMID- 8509305 TI - Electrically evoked auditory brainstem response to stimulation of different sites in the cochlea. AB - It is often assumed that stimulation of the eighth nerve with brief current pulses results in a highly synchronous discharge of action potentials from the ensemble of excited nerve fibers. Latency data derived from the electrically evoked auditory brainstem response (EABR) of the guinea pig and human indicate that there is a baso-apical gradient of response latencies in both species. Place specific stimulation of different regions of the guinea pig cochlea was achieved by positioning a narrowly spaced bipolar electrode into each of the four spiral turns. Peak latencies of EABR waves I and III both revealed longer latencies with increasing distance from the base. Different amplitude growth functions were obtained from each turn. Place-specific stimulation in humans implanted with the Nucleus 22-electrode device was achieved by presenting current pulses across electrodes spaced 1.5 mm apart. A gradient of wave V latencies was observed in all subjects studied. The presence of a latency gradient would influence results obtained in efforts to correlate evoked potential amplitude measures with nerve survival. It may also provide information useful in characterizing the surviving fiber population in human implant subjects. PMID- 8509306 TI - Channel interactions in patients using the Ineraid multichannel cochlear implant. AB - Electrode interactions were investigated on two totally deaf patients fitted with the Ineraid multichannel cochlear implant. Currents were applied to the most apical electrode (the 'perturbation' electrode) and their effects on psychophysical thresholds on the other electrodes (the 'test' electrodes) of the intracochlear array were studied. Two experimental protocols were used. In experiment I, we used a detection protocol to study how the perception of signals presented on each test electrode was affected by subthreshold, simultaneous or non-simultaneous stimulation of the perturbation electrode. Strong electrode interactions were observed with simultaneous stimulation and monotonically decreased as a function of electrode separation. Electrode interactions were weak with non-simultaneous stimulation. In experiment II, we used a discrimination protocol to study how the perception of signals presented on the test electrode was affected by suprathreshold, non-simultaneous stimulation of the perturbation electrode. Subjects could discriminate stimulation of 'perturbation+test' versus 'perturbation alone' when the level of stimulation on the test electrode was near threshold. These results demonstrate that strong electrode interactions in the Ineraid multichannel cochlear implant system are generated by electrical field summation due to simultaneous stimulation of different electrodes, and that one can reduce electrode interactions by sequential activation of the electrodes. These observations might help to understand basic phenomena underlying recent significant improvements in speech recognition scores when switching from simultaneous to interleaved pulsatile stimulation in patients wearing the same cochlear implant system (Wilson et al., 1991). PMID- 8509307 TI - Critical ages in brainstem development revealed by neonatal 3-channel Lissajous' trajectory of auditory brainstem evoked potentials. AB - Auditory brainstem evoked potentials (ABEPs) were recorded from 91 newborns from 7 age groups between 26 to 43 weeks of gestation. In addition to the widely used vertex-mastoid derivation, potentials were recorded from three orthogonal electrode configurations, and represented in 3 dimensional voltage-space as three channel Lissajous' trajectories (3CLTs). ABEPs were evoked by alternating polarity, monaural 75 dBnHL clicks presented at rates of 10/s, 55/s and 80/s. Potentials were also recorded to 45 dBnHL and 15 dBnHL clicks presented at 10/s. 3CLT point by point (apex latencies, amplitudes and orientation) as well as planar segment (planar segment position and duration) descriptors, along with peak latencies of the vertex-mastoid peaks, were followed for effects of age, stimulus intensity and rate. ABEPs began to appear consistently at 29 weeks of gestation to high stimulus intensities, with a rapid decrease of ABEP thresholds up to 34 weeks. At 35 weeks, thresholds stabilized approximately at adult values. The results indicate a significant effect of stimulus rate and intensity as well as of gestational age group on apex latencies. The findings also showed changes in apex orientations associated with stimulus rate and intensity interacting with gestational age. 3CLT descriptors enhanced the understanding of these results in relation to developmental and maturational aspects of the auditory system. The results may be explained by maturational change in relative contributions of constituents of the complex ABEP generators. PMID- 8509308 TI - Confocal laser microscopical images of calcium distribution and intracellular organelles in the outer hair cell isolated from the guinea pig cochlea. AB - We report the use of a confocal laser fluorescence microscope to observe the distribution of cytosolic Ca2+ and the localization of intracellular organelles and cytoskeleton in the isolated outer hair cell (OHC). Membrane-bound Ca2+ stained by chlortetracycline was mainly seen in the subcuticular region, the infranuclear region, and the region adjacent to the lateral wall. In contrast, the central portion of the cytoplasm and nucleus were devoid of detectable fluorescence of membrane-associated Ca2+, but were relatively rich in free Ca2+. The cuticular plate showed a lack of both membrane-bound and free Ca2+. Fluorescent clusters of mitochondria and endoplasmic reticulum were predominantly seen in the infracuticular and infranuclear regions, and some were associated with the lateral wall. These two types of cytosolic organelles which fluoresced upon chlortetracycline treatment are therefore presumed to sequester calcium. The characteristic distribution of the endoplasmic reticulum was observed in coincidence with the infracuticular network of F-actin. The subsurface cistern, which was shown to be analogous to the endoplasmic reticulum in terms of its biological function, is likely to be the source of Ca2+ for the actin-mediated process. PMID- 8509309 TI - Wiener and Volterra analyses applied to the auditory system. AB - The application of a particular branch of non-linear system analysis, the functional series expansion or integral method, to the auditory system is reviewed. Both the Volterra and Wiener approach are discussed and an extension of the Wiener method from its traditional white-noise stimulus approach to that of Poisson distributed clicks is presented. This type of analysis has been applied to compound and single-unit responses from the auditory nerve, cochlear nucleus, auditory midbrain and medial geniculate body. Most studies have estimated only first-order Wiener kernels but in recent years second-order Wiener and Volterra kernels have been estimated, particularly with reference to dynamic non linearities. A particular form of second-order analysis, the Spectro Temporal Receptive Field, offers an alternative to first-order cross-correlation when phase-lock is absent. The correlation method has revealed that neural synchronization is less affected by intensity changes and damage to the hair cells than is neural firing rate. Although the presence of the static cochlear non-linearity could be demonstrated on the basis of the intensity dependence of the first-order Wiener kernel, the identification of the exact form of the nonlinearity of the peripheral auditory system on basis of higher-order Wiener kernels has so far been inconclusive. However, successes of the method can be found in the description of the dynamic non-linearities and non-linear neural interactions. PMID- 8509310 TI - A hydromechanical model of the cochlea with nonlinear feedback using PVF2 bending transducers. AB - A single-channel hydromechanical model of the human cochlea with nonlinear feedback on the membrane is introduced. The piezoelectric transducers for displacement measurement and force exertion on the membrane are constructed of PVF2 in the bimorph bending type. The passive response shows high-frequency slopes of about 60 dB/oct and a shortest wavelength of about 17 mm corresponding to 0.9 Bark in the human cochlea. High-frequency slopes and Q10 dB with one feedback loop are within the range of animal data, where as dynamic compression does not exceed 20 dB. Input impedance and phase response are in good agreement with nature, which is ascribed to longitudinal stiffness of the membrane. PMID- 8509311 TI - Postnatal production of supporting cells in the chick cochlea. AB - The auditory receptor organ in birds, the basilar papilla, is mitotically active after acoustic overstimulation or pharmacological insult and is capable of self repair. The damaged epithelium is repopulated with new hair cells and supporting cells. The cell production that underlies this regenerative self-repair is believed to be a response evoked by damage in populations of cells that normally become mitotically quiescent even before hatching. In contrast, regeneration in the vertebrate nervous system is often correlated with continued or recent neurogenesis in the tissue concerned. The hypothesis that there may be ongoing postnatal production of cells in the normal avian basilar papilla was investigated. Autoradiographic analysis of tritiated-thymidine-injected animals was used to look for the existence of newly formed cells in the basilar papilla of normal posthatch chickens. Several types of supporting cells, namely, organ supporting cells, border cells and hyaline cells, are produced postnatally in the normal chicken. Typically, they are added interstitially to the apical (distal) half of the basilar papilla. PMID- 8509312 TI - Inferred protein content and distribution from density measurements of calcitic and aragonitic otoconia. AB - Otoconia from the peripheral portion of the vestibular system contain specific proteins and are mineralized by several polymorphs of calcium carbonate. To infer the internal distribution of their mineral and protein components, we have measured the densities, by equilibrium centrifugation, and the lengths of aragonitic otoconia from the African clawed frog (Xenopus laevis) and calcitic otoconia from the Norway rat (Rattus norvegicus). The densities are statistically dependent on the length of the otoconia. Further, this dependence is not the same for aragonitic and calcitic otoconia. Aragonitic otoconia are statistically more dense when smaller and less dense when larger. For calcitic otoconia the opposite is true; the smaller otoconia are statistically less dense than larger otoconia. Because the organic and inorganic phases have different densities, this indicates that the otoconial proteins and the mineral phases have different distributions within these two types of otoconia. PMID- 8509313 TI - Effects of aspirin on human auditory filters. AB - Auditory filter shapes were measured in eight male volunteers with normal hearing, using a notched-noise forward-masking paradigm and a signal frequency of 4 kHz. The measurements were made under three conditions: after listeners had taken eight doses of three 320 mg aspirin tablets every six hours; after an identical schedule of placebo ingestion; and one week after testing in the first two conditions had been completed. Half of the listeners did the placebo condition first, and half did the aspirin condition first. Aspirin and placebo were administered double-blind, and testing took place approximately one hour after the last dose. Filter shapes were significantly broader in the aspirin condition than in the placebo and post-test conditions, indicating that even a modest dose affects auditory frequency selectivity. Two-point measures of growth of masking did not differ significantly between conditions. PMID- 8509314 TI - Inner ear basic fibroblast growth factor in CBA/J, C3H/HeJ, and autoimmune Palmerston north mice. AB - Basic fibroblast growth factor (bFGF) has a mitogenic effect on fibroblasts and osteoblasts for matrix proliferation and on endothelial cells for neovascularization. Because otic capsule osteogenesis in autoimmune disease subjects often involves abnormal matrix and vascular changes, bFGF may serve as a potential mediator for such bone disorders. To investigate this relationship, bFGF was evaluated in the Palmerston North autoimmune strain mouse, which develops otic capsule sclerotic lesions during the progression of its systemic disease. Inner ears from PN mice, along with control CBA/J and C3H/HeJ mice, were immunohistochemically stained with antibodies against bFGF to identify its presence and possible role in otic capsule disease. Although cells reactive for bFGF were observed along the lining of the otic capsule in all three strains, a significantly higher frequency was observed in the PN mice. Other sites of staining included connective tissue around the tensor tympani muscle and the geniculate ganglion. This identification of bFGF in the otic capsule raises the possibility that it may play some role in normal bone maintenance, as well as abnormal bone or connective tissue remodeling in autoimmune disease. PMID- 8509315 TI - It's the law. PMID- 8509316 TI - Income, body fatness, and fat patterns in Hispanic women from the Hispanic Health and Nutrition Examination Survey. PMID- 8509317 TI - Trait anger, anger expression, stress, and health status of American and Turkish midlife women. AB - In a cross-cultural study, we investigated the relationships of trait anger, anger expression modes, and stress to physical and mental health in Turkish and American midlife women. Zero-order correlations and multiple regression analyses indicated that regardless of cultural origin, stress was a strong predictor of health status. Stress was negatively related to physical health and positively related to depression. Trait anger, the angry temperament dimension of trait anger, and anger-out were positively related to depression in both American and Turkish women. The negative relationship between somatic mode of anger expression and health was also consistent for both groups. However, anger-in was positively correlated with depression only in American women; suppression of anger was unrelated to health status in Turkish women. Cross-cultural comparisons indicated that Turkish midlife women were higher in trait anger, somatic anger symptoms, perceived stress, and depression than American women. American women, on the other hand, had higher scores on physical health status. These findings are discussed with regard to theory, previous research, and sociocultural context. PMID- 8509318 TI - Korean women's attitudes toward pregnancy and prenatal care. AB - A convenience sample of 40 native-born pregnant Korean women receiving prenatal care at a U.S. military facility in a major metropolitan area in Korea completed a questionnaire about attitudes toward pregnancy and prenatal care. Responses revealed a family life characterized by positive maternal and paternal perceptions of the pregnancy and less preference for a male child than we had anticipated. Traditional beliefs in Tae Mong, a conception dream, and Tae Kyo, rituals for safe childbirth, were followed. Food taboos, including protein sources, were reported. Attitudes toward prenatal care services, care providers, and maternal health habits are described. PMID- 8509319 TI - Mental health of Southeast Asian refugee women: an overview. AB - Southeast Asian refugee women suffered extremely traumatic experiences at the hands of the Khmer Rouge, during their escapes from Cambodia and Laos, and in refugee camps. I describe these experiences as the background for interventions to promote and re-establish mental health in these women. A reported study of women who were experiencing psychosomatic blindness as a result of the trauma they had undergone is presented as an example. Therapeutic strategies are suggested. PMID- 8509320 TI - Mood changes in women after an aerobics class: a preliminary study. AB - The psychological benefits of physical exercise have been well documented. Acute exercise (typically running) has been reported to improve mood, decrease anxiety, and increase vigor. Aerobics classes are increasing in popularity among women, and to investigate mood changes in women after an aerobics class, we asked 45 high-frequency and 52 low-frequency exercisers to complete a specially devised mood adjective checklist 5 min before and immediately after a class. Principal components analysis revealed three dimensions that emerged on both occasions: Positive Mood, Negative Mood, and Fatigue. Component subscale scores were calculated for each woman for each occasion. Significant differences in mood before and after the class emerged. Increased positive affect and decreased negative affect after the class were reported. Fatigue was also reduced. The high and low exercisers experienced the same degree of mood change. PMID- 8509321 TI - The portrayal of the menstruating woman in menstrual product advertisements. AB - Because menstrual product advertisements act as mediators of a subset of meanings of femininity linked to menstruation, we performed a comparative conceptual analysis of these advertisements to explicate media-constructed realities of contemporary women. We sought to understand the portrayed women's definition of menstruation and their status as menstruating women. Textual and conceptual analyses led us to conclude that the portrayed women, in an attempt to avoid others' discovery of their menstruation, employed a complex menstrual management system, which often includes feminized menstrual products, to act as an antidote to a tainted state of femininity. PMID- 8509322 TI - Clients undergoing chorionic villus sampling versus amniocentesis: contrasting attitudes toward pregnancy. AB - We analyzed interview data from 44 primarily white, middle-class women who had used the prenatal diagnostic technique of chorionic villus sampling (CVS: n = 24) or amniocentesis (n = 20). CVS provides earlier results but carries a somewhat higher risk of miscarriage. Amniocentesis clients were highly committed to the pregnancy and expressed considerable anxiety over the possibility of having to terminate it should an abnormality be diagnosed. CVS clients seemed less bonded to the fetus and less concerned about losing a pregnancy several termed "replaceable." Thus, with its first-trimester abortion decision, CVS redefines prenatal diagnostic issues for women. PMID- 8509323 TI - Infant temperament and postpartum depression: a review. AB - Although limited in number, reported research studies indicate a relationship between maternal perceptions of infant temperament and postpartum depression. Excessive crying in particular and the extent of adaptability and predictability have been implicated as infant behavioral indices. In this article, we present the results of a review of the literature linking early infant temperament to postpartum depression. Measurement issues for both infant temperament and depression are discussed. Recommendations for future research are offered. PMID- 8509324 TI - DNA sequence and mutational analysis of genes involved in the production and resistance of the antibiotic peptide trifolitoxin. AB - The 7.1-kb fragment of Rhizobium leguminosarum bv. trifolii T24 DNA which confers trifolitoxin production and resistance to nonproducing, sensitive Rhizobium strains (E. W. Triplett, M. J. Schink, and K. L. Noeldner, Mol. Plant-Microbe Interact. 2:202-208, 1989) was subcloned, sequenced, and mutagenized with a transcriptional fusion cassette. The sequence of this fragment revealed seven complete open reading frames, tfxABCDEFG, all transcribed in the same direction. TfxA has an 11-amino-acid carboxy terminus identical to the known amino acid sequence of the trifolitoxin backbone, DIGGSRXGCVA, where X is an UV-absorbing chromophore. This is evidence that trifolitoxin is synthesized ribosomally as a prepeptide that is posttranslationally modified to yield the active peptide. TfxB shows 27.6% identity with McbC, a protein required for the production of the ribosomally synthesized antibiotic microcin B17. Tn3GUS transcriptional fusion insertions in tfxA, tfxB, tfxD, or tfxF caused a nonproducing, trifolitoxin resistant phenotype and confirmed the direction of transcription of these frames. No insertion mutations were found in tfxE or tfxG. Sequence analysis along with insertion and deletion mutation analysis suggest that (i) trifolitoxin is synthesized ribosomally from tfxA; (ii) tfxA, tfxE, and tfxG have their own promoters; (iii) TfxG is required for immunity; (iv) TfxB, TfxD, and TfxF are required for trifolitoxin production; and (v) the UV-absorbing chromophore is derived from glutamine. PMID- 8509325 TI - Developmental regulation of the gene for formate dehydrogenase in Neurospora crassa. AB - We have isolated and characterized a gene, fdh, from Neurospora crassa which is developmentally regulated and which produces formate dehydrogenase activity when expressed in Escherichia coli. The gene is closely linked (less than 0.6 kb apart) to the leu-5 gene encoding mitochondrial leucyl-tRNA synthetase; the two genes are transcribed convergently from opposite strands. The expression patterns of these genes differ: fdh mRNA is found only during conidiation and early germination and is not detectable during mycelial growth, while leu-5 mRNA appears during germination and mycelial growth. The structure of the fdh gene was determined from the sequence of cDNA and genomic DNA clones and from mRNA mapping studies. The gene encodes a 375-amino-acid-long protein with sequence similarity to NAD-dependent dehydrogenases of the E. coli 3-phosphoglycerate dehydrogenase (serA gene product) subfamily. In particular, there is striking sequence similarity (52% identity) to formate dehydrogenase from Pseudomonas sp. strain 101. All of the residues thought to interact with NAD in the crystal structure of the Pseudomonas enzyme are conserved in the N. crassa enzyme. We have further shown that expression of the N. crassa gene in E. coli leads to the production of formate dehydrogenase activity, indicating that the N. crassa gene specifies a functional polypeptide. PMID- 8509327 TI - Regulation of glycerol metabolism in Enterococcus faecalis by phosphoenolpyruvate dependent phosphorylation of glycerol kinase catalyzed by enzyme I and HPr of the phosphotransferase system. AB - Using a polyclonal antibody against glycerol kinase from Enterococcus faecalis, we could demonstrate that glycerol kinase is inducible by growth on glycerol containing medium and that during growth on glycerol the enzyme is mainly phosphorylated. Glucose and other sugars metabolized via the Embden-Meyerhof pathway strongly repressed the synthesis of glycerol kinase, while if glycerol was also present during growth, low activity, reflecting partial induction and the presence of mainly unphosphorylated, less active enzyme, was found. With gluconate, which is also a substrate of the phosphotransferase system, repression of glycerol kinase was less severe, but the enzyme was mainly present in the less active, unphosphorylated form. Effects of growth on different carbon sources on glycerol uptake are also reported. PMID- 8509326 TI - Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB. AB - Thiolactomycin (TLM) and cerulenin are antibiotics that block Escherichia coli growth by inhibiting fatty acid biosynthesis at the beta-ketoacyl-acyl carrier protein synthase I step. Both TLM and cerulenin trigger the accumulation of intracellular malonyl-coenzyme A coincident with growth inhibition, and the overexpression of synthase I protein confers resistance to both antibiotics. Strain CDM5 was derived as a TLM-resistant mutant but remained sensitive to cerulenin. TLM neither induced malonyl-coenzyme A accumulation nor blocked fatty acid production in vivo; however, the fatty acid synthase activity in extracts from strain CDM5 was sensitive to TLM inhibition. The TLM resistance gene in strain CDM5 was mapped to 57.5 min of the chromosome and was an allele of the emrB gene. Disruption of the emrB gene converted strain CDM5 to a TLM-sensitive strain, and the overexpression of the emrAB operon conferred TLM resistance to sensitive strains. Thus, activation of the emr efflux pump is the mechanism for TLM resistance in strain CDM5. PMID- 8509328 TI - Analysis of proteins synthesized by Salmonella typhimurium during growth within a host macrophage. AB - Salmonella typhimurium is a facultative intracellular pathogen, able both to invade and to survive within eukaryotic cells and to grow in various extracellular environments. To compare the bacterial responses to these disparate environments and to shed light on the nature of the intracellular environment, we have examined the pattern of protein synthesis by two-dimensional polyacrylamide gel electrophoresis. The levels of approximately 40 proteins were observed to increase during growth within macrophage-like U937 cells, while approximately 100 proteins exhibited levels that were repressed relative to those of an extracellular control culture. To aid in the interpretation of these results, the patterns of proteins made by S. typhimurium exposed to various environmental conditions in the laboratory were determined. The intracellular protein pattern was then compared with each of these benchmark protein patterns. This analysis revealed that, as expected, the intracellular environment appears to impose numerous stresses on the bacteria, but unexpectedly, the macrophage-induced response was not a simple sum of the individual stress responses displayed during extracellular growth. PMID- 8509329 TI - Growth rate paradox of Salmonella typhimurium within host macrophages. AB - The growth rate of Salmonella typhimurium U937 within host macrophages was estimated by two independent methods. The extent to which ribosomal protein L12 is acetylated to produce ribosomal protein L7 changes markedly with the growth rate. By this measure, the intracellular bacteria appeared to be growing rapidly. Measurements of viable bacteria, however, indicated that the bacteria were growing slowly. A solution of this apparent growth rate paradox was sought by treating U937 cells infected with S. typhimurium X3306 with ampicillin or chloramphenicol to help determine the number of bacteria that were actively growing and dividing in the intracellular condition. Use of these antibiotics showed that by 2 h after invasion, the intracellular bacteria consisted of at least two populations, one static and the other rapidly dividing. This finding implies that previously described changes in the gene expression of S. typhimurium are important for the survival and/or multiplication of the bacteria within the macrophage. PMID- 8509330 TI - Bacillus subtilis transcription regulator, Spo0A, decreases alkaline phosphatase levels induced by phosphate starvation. AB - Alkaline phosphatase (APase) is induced as a culture enters stationary phase because of limiting phosphate. The results presented here show that expression of APase is regulated both negatively and positively. PhoP, a homolog of a family of bacterial transcription factors, and PhoR, a homolog of bacterial histidine protein kinases, are required for induction of APases when phosphate becomes limiting. The induction period lasts 2 to 3 h, after which the rate of APase accumulation is decreased. Mutant strains defective in the Spo0A transcription factor failed to decrease APase production. The consequent hyperinduction of APase in a spo0A strain was dependent on phoP and phoR. spo0B and spo0F strains also overexpressed APase, suggesting that phosphorylated Spo0A is required for repression of APase. An abrB mutant allele in the presence of the mutant spo0A allele in these strains did not significantly change the APase hyperinduction phenotype, demonstrating that Spo0A repression of abrB expression is not the mechanism by which Spo0A-P regulates APase expression. Our previous report that spo0A mutants do not express APases is in conflict with the present data. We show here that the previously used mutants and a number of commonly used spo0 strains, all of which have an APase deficiency phenotype, contain a previously unrecognized mutation in phoR. PMID- 8509331 TI - Cloning and characterization of a cluster of genes encoding polypeptides present in the insoluble fraction of the spore coat of Bacillus subtilis. AB - The Bacillus subtilis spore coat is composed of at least 15 polypeptides plus an insoluble protein fraction arranged in three morphological layers. The insoluble fraction accounts for about 30% of the coat protein and is resistant to solubilization by a variety of reagents, implying extensive cross-linking. A dodecapeptide was purified from this fraction by formic acid hydrolysis and reverse-phase high-performance liquid chromatography. This peptide was sequenced, and a gene designated cotX was cloned by reverse genetics. The cotX gene encoding the dodecapeptide at its amino end was clustered with four other genes designated cotV, cotW, cotY, and cotZ. These genes were mapped to 107 degrees between thiB and metA on the B. subtilis chromosome. The deduced amino acid sequences of the cotY and cotZ genes are very similar. Both proteins are cysteine rich, and CotY antigen was present in spore coat extracts as disulfide cross-linked multimers. There was little CotX antigen in the spore coat soluble fraction, and deletion of this gene resulted in a 30% reduction in the spore coat insoluble fraction. Spores produced by strains with deletions of the cotX, cotYZ, or cotXYZ genes were heat and lysozyme resistant but readily clumped and responded more rapidly to germinants than did spores from the wild type. In electron micrographs, there was a less densely staining outer coat in spores produced by the cotX null mutant, and those produced by a strain with a deletion of the cotXYZ genes had an incomplete outer coat. These proteins, as part of the coat insoluble fraction, appear to be localized to the outer coat and influence spore hydrophobicity as well as the accessibility of germinants. PMID- 8509332 TI - Genetics of serine pathway enzymes in Methylobacterium extorquens AM1: phosphoenolpyruvate carboxylase and malyl coenzyme A lyase. AB - Methylobacterium extorquens AM1 is a facultative methylotrophic bacterium that uses the serine pathway for formaldehyde incorporation as its assimilation pathway during growth on one-carbon compounds. A DNA region from M. extorquens AM1 previously shown to contain genes for the serine pathway enzymes malyl coenzyme A (CoA) lyase and hydroxypyruvate reductase has been characterized in more detail. Insertion mutagenesis revealed an additional region required for growth on one-carbon compounds, and all of the insertion mutants in this region lacked activity for another serine pathway enzyme, the acetyl-CoA-independent phosphoenolpyruvate (PEP) carboxylase. Expression analysis with Escherichia coli of DNA fragments that included the malyl-CoA lyase and PEP carboxylase regions identified five polypeptides, all transcribed in the same direction. Three of these polypeptides were expressed from the region necessary for the acetyl-CoA independent PEP carboxylase, one was expressed from the region containing the malyl-CoA lyase gene, and the fifth was expressed from a region immediately downstream from the gene encoding hydroxypyruvate reductase. All six genes are transcribed in the same direction, but the transposon insertion data suggest that they are not all cotranscribed. PMID- 8509333 TI - Cloning and characterization of ftsN, an essential cell division gene in Escherichia coli isolated as a multicopy suppressor of ftsA12(Ts). AB - A new cell division gene, ftsN, was identified in Escherichia coli as a multicopy suppressor of the ftsA12(Ts) mutation. Remarkably, multicopy ftsN suppressed ftsI23(Ts) and to a lesser extent ftsQ1(Ts); however, no suppression of the ftsZ84(Ts) mutation was observed. The suppression of ftsA12(Ts), ftsI23(Ts), and ftsQ1(Ts) suggests that FtsN may interact with these gene products during cell division. The ftsN gene was located at 88.5 min on the E. coli genetic map just downstream of the cytR gene. ftsN was essential for cell division, since expression of a conditional null allele led to filamentation and cell death. DNA sequence analysis of the ftsN gene revealed an open reading frame of 319 codons which would encode a protein of 35,725 Da. The predicted gene product had a hydrophobic sequence near its amino terminus similar to the noncleavable signal sequences found in several other Fts proteins. The presumed extracellular domain was unusual in that it was rich in glutamine residues. A 36-kDa protein that was localized to the membrane fraction was detected in minicells containing plasmids with the ftsN gene, confirming that FtsN was a membrane protein. PMID- 8509334 TI - Identification, isolation, and characterization of the structural gene encoding the delta' subunit of Escherichia coli DNA polymerase III holoenzyme. AB - The gene encoding the delta' subunit of DNA polymerase III holoenzyme, designated holB, was cloned by a strategy in which peptide sequence was used to derive a DNA hybridization probe. The gene maps to 24.95 centisomes of the chromosome. Sequencing of holB revealed a 1,002-bp open reading frame predicted to produce a 36,936-Da protein. The gene has a ribosome-binding site and promoter that are highly similar to the consensus sequences and is flanked by two potential open reading frames. Protein sequence analysis of delta' revealed a high degree of similarity to the dnaX gene products of Escherichia coli and Bacillus subtilis, including one stretch of 10 identical amino acid residues. A lesser degree of similarity to the gene 44 protein of bacteriophage T4 and the 40-kDa protein of the A1 complex (replication factor C) of HeLa cells was seen. The gene, when placed into a tac promoter-based expression plasmid, directed expression of two proteins of similar size. By immunodetection with anti-holoenzyme immunoglobulin G, both proteins are judged to be products of holB. PMID- 8509336 TI - Construction and characterization of a phage-plasmid hybrid (phagemid), pCAK1, containing the replicative form of viruslike particle CAK1 isolated from Clostridium acetobutylicum NCIB 6444. AB - A bacteriophage-plasmid hybrid (phagemid) designated pCAK1 was constructed by ligating 5-kbp Escherichia coli plasmid pAK102 (AprEmr) and the 6.6-kbp HaeIII linearized replicative form of the CAK1 viruslike particle from Clostridium acetobutylicum NCIB 6444. Phagemid pCAK1 (11.6 kbp) replicated via the ColE1 replication origin derived from pAK102 in E. coli. Single-stranded DNA (ssDNA) molecules complexed with protein in a manner which protected ssDNA from nucleases were recovered from the supernatant of E. coli DH11S transformants containing pCAK1 in the absence of cell lysis. This suggests that the viral-strand DNA synthesis replication origin of CAK1 and associated gene expression are functional in E. coli DH11S. The single-stranded form of pCAK1 isolated from E. coli supernatant was transformed into E. coli DH5 alpha' or DH11S by electroporation. Isolation of ampicillin-resistant E. coli transformants following transformation suggests that the complementary-strand DNA synthesis replication origin of CAK1 is also functional in E. coli. The coat proteins associated with ssDNA of pCAK1 demonstrated sensitivity to proteinase K and various solvents (i.e., phenol and chloroform), similar to the results obtained previously with CAK1. Following phagemid construction in E. coli, pCAK1 was transformed into C. acetobutylicum ATCC 824 and C. perfringens 13 by intact cell electroporation. Restriction enzyme analysis of pCAK1 isolated from erythromycin resistant transformants of both C. acetobutylicum and C. perfringens suggested that it was identical to that present in E. coli transformants. PMID- 8509335 TI - SSG1, a gene encoding a sporulation-specific 1,3-beta-glucanase in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, the meiotic process is accompanied by a large increase in 1,3-beta-glucan-degradative activity. The molecular cloning of the gene (SSG1) encoding a sporulation-specific exo-1,3-beta-glucanase was achieved by screening a genomic library with a DNA probe obtained by polymerase chain reaction amplification using synthetic oligonucleotides designed according to the nucleotide sequence predicted from the amino-terminal region of the purified protein. DNA sequencing indicates that the SSG1 gene specifies a 445-amino-acid polypeptide (calculated molecular mass, 51.8 kDa) showing extensive similarity to the extracellular exo-1,3-beta-glucanases encoded by the EXG1 gene (C. R. Vazquez de Aldana, J. Correa, P. San Segundo, A. Bueno, A. R. Nebreda, E. Mendez, and F. del Rey, Gene 97:173-182, 1991). The N-terminal domain of the putative precursor is a very hydrophobic segment with structural features resembling those of signal peptides of secreted proteins. Northern (RNA) analysis reveals a unique SSG1 specific transcript, 1.7 kb long, which can be detected only in sporulating diploids (MATa/MAT alpha) but does not appear in vegetatively growing cells or in nonsporulating diploids (MAT alpha/MAT alpha) when incubated under nitrogen starvation conditions. The meiotic time course of SSG1 induction indicates that the gene is transcribed only in the late stages of the process, beginning at the time of meiosis I and reaching a maximum during spore formation. Homozygous ssg1/ssg1 mutant diploids are able to complete sporulation, although with a significant delay in the appearance of mature asci. PMID- 8509338 TI - Biosynthesis and stereochemistry of the autoinducer controlling luminescence in Vibrio harveyi. AB - Knowledge of the pathway for synthesis of the autoinducer, N-(beta hydroxybutyryl)-homoserine lactone (HBHL), controlling luminescence in Vibrio harveyi can provide important information concerning the relationship between the nutrition and physiology of the bacteria and the phenomenon of light emission. In this study, the D and L isomers of the autoinducer containing the stereoisomers of beta-hydroxybutyric acid were synthesized and characterized by proton nuclear magnetic resonance in the presence of a chiral shift reagent, a europium(III) derivative of Tris[3-(heptafluoropropyl-hydroxymethylene)-(+)-camphorato]. By using a newly isolated autoinducer mutant which responds to low physiological concentrations of the autoinducer, it could be shown that autoinducer activity was associated with D-HBHL and not L-HBHL. Blockage of fatty acid biosynthesis by the addition of fatty acids and/or the antibiotic cerulenin to the cells prevented synthesis of the autoinducer as measured by the loss of autoinducer activity and a decrease in the incorporation of labelled acetate into the partially purified autoinducer. These results indicate that fatty acid biosynthesis is necessary for light emission in luminescent bacteria because it controls formation of the lux autoinducer. PMID- 8509337 TI - Vibrio parahaemolyticus has a homolog of the Vibrio cholerae toxRS operon that mediates environmentally induced regulation of the thermostable direct hemolysin gene. AB - In an effort to identify the regulatory gene controlling the expression of the tdh gene, encoding the thermostable direct hemolysin of Vibrio parahaemolyticus, we examined total DNA of AQ3815 (a Kanagawa phenomenon-positive strain) for sequences homologous to that of the toxR gene of Vibrio cholerae. The extracted DNA gave a weak hybridization signal under reduced-stringency conditions with a toxR-specific DNA probe. Cloning and sequence analysis of the probe-positive sequence revealed an operon (Vp-toxRS) which was highly similar to the toxRS operon of V. cholerae (Vc-toxRS) (52 and 62% similarities in the two genes, respectively). The deduced amino acid sequences of the Vp-toxRS gene products (Vp ToxRS) contained regions similar to the proposed transmembrane and activity domains of the Vc-toxRS gene products (Vc-ToxRS). All clinical and environmental strains of V. parahaemolyticus examined possessed the Vp-toxRS genes. In the presence of Vp-ToxS, Vp-ToxR promoted expression of the tdh2 gene, one of two tdh genes (tdh1 and tdh2) carried by Kanagawa phenomenon-positive strains. The DNA sequence located 144 bp upstream of the tdh2 coding region was shown to be important for the Vp-ToxR-stimulated expression of the tdh2 gene in an Escherichia coli background. Comparative analysis of AQ3815 and its isogenic Vp toxR null mutant gave the following results: (i) Vp-ToxR promoted, in an AQ3815 background, expression of the tdh gene to different degrees in various culture media, with KP broth (2% peptone, 0.5% NaCl, 0.03 M KH2PO4, pH 6.2) being most effective (12-fold); (ii) the promotion of tdh gene expression in KP broth was at the level of transcription; and (iii) Vp-ToxR was essential for demonstration of enterotoxic activity of AQ3815 in the rabbit ileal loop, a model previously used to demonstrate thermostable direct hemolysin-mediated enterotoxic activity of AQ3815. These results demonstrate that Vp-ToxR and Vc-ToxR share a strikingly similar function, i.e., direct stimulation at the transcriptional level of the gene encoding a major virulence determinant (enterotoxin) of a Vibrio species. PMID- 8509339 TI - Nucleotide sequences and heterologous expression of tcmG and tcmP, biosynthetic genes for tetracenomycin C in Streptomyces glaucescens. AB - The nucleotide sequence of the tcmIII, tcmIc, and tcmVII region of the tetracenomycin (TCM) C gene cluster of Streptomyces glaucescens ETH 22794 (GLA.0) revealed the presence of two genes, tcmP and tcmG. The deduced product of tcmG resembles flavoprotein hydroxylases found in several other bacteria, whereas the predicted amino acid sequence of tcmP is not significantly similar to those of any known proteins in the available data bases. Southern blot hybridization revealed an approximately 180-bp deletion in a tcmIII (tcmG) mutant and a 1,800 bp insertion in a tcmVII (tcmP) mutant. Heterologous expression of tcmG and tcmP in Streptomyces lividans and tcmP in Escherichia coli established that tcmP encodes an O-methyltransferase, catalyzing the methylation of the C-9 carboxy group of TCM E to yield TCM A2, and that tcmG is responsible for the hydroxylation of TCM A2 at positions C-4, C-4a, and C-12a to give TCM C. These are the final two steps of TCM C biosynthesis. PMID- 8509341 TI - Copy number of the 16S rRNA gene in Rickettsia prowazekii. AB - The obligate intracellular parasite, Rickettsia prowazekii, is a slowly growing bacterium with a doubling time of 8 to 12 h. The copy number of the 16S rRNA gene in the rickettsial chromosome was determined to be one. Genomic DNA from R. prowazekii was digested either by a variety of restriction enzymes known not to cut at any site in the rickettsial 16S rRNA gene or by a combination of these noncutting enzymes and SmaI, which cuts the gene only once. Only one DNA fragment in these digests hybridized to a biotinylated probe containing a portion of the rickettsial 16S rRNA gene. Moreover, the density of the rickettsial 16S rRNA gene fragment after hybridization was equal to the density of each of the seven 16S rRNA gene fragments in Escherichia coli. PMID- 8509340 TI - Transcriptional analysis of the Streptomyces glaucescens tetracenomycin C biosynthesis gene cluster. AB - A 12.6-kb DNA fragment from Streptomyces glaucescens GLA.0 containing the 12 genes for tetracenomycin (TCM) C biosynthesis and resistance enabled Streptomyces lividans to produce TCM C. Transcriptional analysis of the tcmPG intergenic region in this cluster established the presence of two divergent promoters. The tcmIc mutation, a T-to-G transversion in the -10 region of the tcmG promoter, decreased promoter activity drastically at the stationary growth stage and time of maximum TCM C accumulation. This promoter may direct the transcription of a tcmGHIJKLMNO operon, while the other promoter is for tcmP. PMID- 8509342 TI - The Salmonella typhimurium uracil-sensitive mutation use is in argU and encodes a minor arginine tRNA. AB - The use gene of Salmonella typhimurium was previously identified by a mutation conferring sensitivity to uracil in glucose minimal medium. The use gene was cloned and identified as an allele of argU encoding a tRNA for a minor arginine codon (CGG). The uracil-sensitive phenotype was shown to result from a base substitution in the anticodon stem of this tRNA. PMID- 8509343 TI - Cloning and sequencing of a gene encoding carminomycin 4-O-methyltransferase from Streptomyces peucetius and its expression in Escherichia coli. AB - Sequence analysis of a portion of the Streptomyces peucetius daunorubicin biosynthetic gene cluster revealed a complete open reading frame (dnrK) that showed DNA and protein sequence homology to several O-methyltransferases. Expression of dnrK in Streptomyces lividans and Escherichia coli was done to show that this gene codes for carminomycin 4-O-methyltransferase. The deduced carminomycin 4-O-methyltransferase protein shows a conserved nucleotide binding site for its S-adenosyl-L-methionine cofactor. PMID- 8509344 TI - Phi X174 E complements lambda S and R dysfunction for host cell lysis. AB - Hybrid lambda phages which have the E lysis gene of the bacteriophage phi X174 in cis to defective nonsense and deletion alleles of the normal lambda lysis genes S and R have been constructed and shown to be fully competent for plaque-forming ability, which demonstrates that the single-gene, lysozyme-independent lysis system of phi X174 and related phages can serve the lytic function for large complex phages. These hybrid phages are unable to form plaques on a slyD host. Moreover, plaque morphology indicates that in E-mediated lysis the soluble lambda R endolysin can participate in lysis, indicating that the protein E-mediated lesions are not completely sealed off from the periplasm. PMID- 8509345 TI - Leptospira genomes are modified at 5'-GTAC. AB - Genomic DNAs of 14 strains from seven species of the spirochete Leptospira were resistant to cleavage by the restriction endonuclease RsaI (5'-GTAC). A modified base comigrating with m4C was detected by chromatography. Genomic DNAs from other spirochetes, Borrelia group VS461, and Serpulina strains were not resistant to RsaI digestion. Modification at 5'-GTAm4C may occur in most or all strains of all species of Leptospira but not in all genera of spirochetes. Genus-wide DNA modification has rarely been observed in bacteria. PMID- 8509346 TI - Plasmid pT181-linked suppressors of the Staphylococcus aureus pcrA3 chromosomal mutation. AB - Plasmid pT181 replication is affected in hosts carrying the chromosomal pcrA3 mutation, resulting in significantly lower plasmid copy numbers. Mutations suppressing this effect have been isolated and characterized. The suppressor mutations were found to map in the plasmid repC gene and manifested pcrA allele specificity, suggesting the existence of a direct RepC-PcrA interaction. PMID- 8509347 TI - The relationship between depression and length of stay in the general hospital patient. AB - BACKGROUND: Depression is believed to complicate the care of general hospital patients on medical and surgical wards. How to compare dissimilar medical disorders and the degree of illness has been problematic. METHOD: All patients evaluated during a 6-month period by one consultation-liaison service who received a DSM-III-R diagnosis of depression were retrospectively compared with a control group without any depressive symptoms who were admitted to the same medical-surgical units over the identical period of time. The two groups were matched by primary diagnostic related groups (DRGs) and had equivalent severity of illness scores (APACHE II). RESULTS: The depressed group had a mean length of stay 10 days longer than did the control group (t = 2.42, p < .02). Depressed patients who were treated with antidepressants and supportive therapy at the time of consultation by a psychiatrist (N = 15, 83%) had a mean length of stay 31.8 days shorter than those whose major depression was not treated (N = 3, 17%) (t = 2.19, p < .04). CONCLUSION: Matching depressed patients having a variety of physical illnesses to a nondepressed group having the same primary DRGs and equivalent severity of illness demonstrates the impact of comorbidity on length of stay and potential health care costs. PMID- 8509348 TI - Low-dose oral medroxyprogesterone acetate in the management of the paraphilias. AB - BACKGROUND: There are no reports on the use of low-dose oral medroxyprogesterone acetate (MPA) in the treatment of the paraphilias. High-dose depot MPA treatment (500-800 mg i.m. weekly) has proven to control the behavioral manifestations of the paraphilias when testosterone levels decrease from pretreatment to prepubescent levels, but at the price of significant morbidity. METHOD: Oral MPA (60 mg/day for an average of 15.33 months) was given in an open nonblind trial to seven patients who met criteria for DSM-III-R paraphilias. Four of the subjects had shown inadequate improvement after 1 year of psychotherapy. RESULTS: Six subjects responded at 60 mg/day. Testosterone levels decreased by 50% to 75% (range, 100-400 ng/dL). No patient displayed significant side effects. All patients described significantly fewer paraphilic fantasies, and no patient reported engaging in paraphilic behaviors during oral MPA treatment. CONCLUSION: Double-blind placebo and phallometrically controlled tumescence studies need to be carried out to test the results of this study. PMID- 8509349 TI - Trazodone in benzodiazepine dependence. AB - BACKGROUND: The authors set forth to test the usefulness of trazodone as an alternative anxiolytic in benzodiazepine-dependent patients. METHOD: Ten benzodiazepine-dependent patients according to DSM-III-R were hospitalized during a 2-4 week period and treated with trazodone (100 mg t.i.d.) while their benzodiazepine intake was progressively tapered; they left the hospital on a regimen of only a 300-mg daily dose of trazodone and were followed as outpatients at monthly intervals. The dose of trazodone was individually adapted according to condition. RESULTS: Very limited withdrawal phenomena occurred during the benzodiazepine taper period; during the 1-year follow-up, all patients remained off benzodiazepines and showed no evidence of abuse of trazodone. The dose of trazodone was significantly reduced to 185 mg (p = .003); the ratings of anxiety and depressive symptoms also significantly improved during follow-up: from 12.3 to 5.4 on the Hamilton Rating Scale for Anxiety (p = .002) and from 11.6 to 4.8 on the Hamilton Rating Scale for Depression (p = .002). CONCLUSION: These findings suggest the usefulness of trazodone as an alternative anxiolytic in patients at risk for benzodiazepine abuse. PMID- 8509350 TI - Gonadotropin-releasing hormone agonist in treatment of premenstrual symptoms with and without comorbidity of depression: a pilot study. AB - BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) in depot form for once a-month rather than daily injection was examined in a small open trial to determine the extent of reduction of premenstrual symptoms, particularly premenstrual "depression." METHOD: Women who met criteria for premenstrual syndrome (PMS) or for PMS with comorbidity of major depression (MD), based on DSM III-R criteria, were evaluated for the study. Evaluation included Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and Daily Symptom Report (DSR), maintained throughout the study. Seven PMS subjects and two subjects who met the severity and change criteria for PMS but had concurrent MD were administered 3.75 mg of depot leuprolide monthly. Symptom change as reported on the DSR was compared with the untreated baseline scores. RESULTS: Six of seven PMS subjects had cessation of menses and significant decreases in premenstrual symptoms (p < .0001), which were reduced to their follicular phase levels. Physical symptoms of swelling and breast tenderness were among the most improved symptoms. Despite cessation of menses, the two MD subjects showed little improvement in premenstrual symptoms and no improvement in depressive symptoms. The premenstrual depression scores decreased almost completely in the PMS subjects, but increased slightly in the MD subjects. CONCLUSION: This small open trial suggests that GnRH agonist therapy reduces premenstrual symptoms including "depression" in women who meet criteria for PMS but not in women with PMS and MD. Further controlled study of the role of ovarian function in mood disorders is needed. PMID- 8509351 TI - Mania and cough syrup. PMID- 8509352 TI - Mania and cough syrup. PMID- 8509353 TI - Treatment of hypochondriasis with clomipramine. PMID- 8509354 TI - Monitoring antidepressant-induced cerebral hyperexcitability. PMID- 8509355 TI - Advancing age may inhibit antidepressant-induced seizure. PMID- 8509356 TI - The treatment of anxiety in patients with alcoholism. AB - The high incidence and the high comorbidity of alcohol and anxiety problems make the relationship between these two disorders one of the most important issues clinicians have to address. However, many general psychiatrists have had minimal training in treating patients with addictions, and many experts on alcoholism have not fully mastered the armamentarium of approaches to treating anxiety. In general, special problems exist in treating anxiety in patients with alcoholism, particularly in those patients with anxiety disorders. The clinician must analyze and treat the complicated interaction between these disorders and target the right combination and sequences of treatment fitting the specific needs of the case. The effects of intoxication, withdrawal, and chronic use on anxiety and need to be taken into account and the primary vs. secondary nature of the disorders needs to be determined. Parameters for choosing setting, modality, pharmacologic approaches, and issues in treating special populations will be discussed. Decisions about treatment should be based on sound knowledge of the epidemiology, diagnostic issues, genetics, pathophysiology, biological aspects, clinical course, complications, and treatment-outcome studies of anxiety and alcohol disorders. The wise clinician also needs to show flexibility in approaching treatment-resistant cases. PMID- 8509357 TI - Mixed anxiety and depression: should it be included in DSM-IV? AB - DSM-IV is provisionally including a category of mixed anxiety and depression for several reasons. First, it will be included in ICD-10, and therefore used worldwide. The ICD-10 category and the mixed anxiety and depression category now being included in the appendix of DSM-IV are subsyndromal in that they include patients with both anxious and depressive symptoms that fail to meet criteria for an established anxiety or depression diagnosis. Primary-care physicians regularly report a high incidence of patients whose symptoms fit this subsyndromal definition of mixed anxiety and depression. Such patients are not easily classifiable using DSM-III or DSM-III-R criteria, yet they often manifest sufficient distress and/or disability to require treatment. Those who oppose establishing the diagnosis of mixed anxiety and depression make the following points: (1) patients considered eligible for this diagnosis will actually meet criteria for a current DSM disorder; (2) mixed anxiety and depression will become a "wastebasket" category for a heterogeneous group of patients; (3) if any new subsyndromal diagnosis is needed, minor depression should suffice; and (4) mixed anxiety and depression will overlap extensively with adjustment reaction. PMID- 8509358 TI - Therapeutic strategies for the patient with treatment-resistant anxiety. AB - Outcome of anxiety disorder treatment with psychotherapy and medication is generally as good as or better than that of other psychiatric illnesses. Nevertheless, refractory cases occur. The first step in approaching the treatment resistant patient with an anxiety disorder is to be certain that the treatment has been adequate. Failure to provide an adequate dose of medication for adequate periods of time may be the most common cause of "treatment resistance." The second step is to reconsider the diagnosis and/or determine if new diagnoses have emerged since the original consultation. Depression and substance abuse are especially likely to complicate anxiety disorders. Several studies have shown that concomitant personality disorders (axis II) increase the occurrence of resistance to standard treatment and must be addressed through psychotherapy. Last, a variety of possible underlying medical conditions, including thyroid disorder, arrhythmia, and complex partial seizure, should be considered. Then, the clinician should consider a variety of pharmacologic approaches that are specific to each anxiety disorder. Panic disorder patients who are refractory to imipramine frequently respond to high-potency benzodiazepines, monoamine oxidase (MAO) inhibitors, serotonin reuptake inhibitors, or various combinations. Generalized anxiety disorder, if unresponsive to benzodiazepines, may respond to buspirone or a tricyclic antidepressant. Patients with obsessive compulsive disorder who have failed to respond to clomipramine or fluoxetine and other serotonin reuptake blockers may benefit from augmentation strategies using combination therapies including buspirone, fenfluramine, and neuroleptics. Social phobia refractory to beta-blockers and MAO inhibitors may benefit from buspirone, fenfluramine, and neuroleptics. Social phobia refractory to beta-blockers and MAO inhibitors may benefit from buspirone, fluoxetine, or alprazolam. PMID- 8509359 TI - The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat. AB - The human CD44 cell surface glycoprotein family which has been implicated in lymphocyte homing, tumor metastasis, and extracellular matrix attachment consists of a large number of related isoforms that derive from the differential splicing of a single CD44 gene transcript. Recent mapping of the CD44 locus in man indicated the presence of at least nine alternative exons within the region of the gene encoding the variable membrane proximal extracellular domain. Here we report the identification of a 10th alternative exon (termed V1) in the mouse, human, and rat CD44 genes. We demonstrate tissue-specific patterns of expression for transcripts containing exons V1-V10 in the mouse and a highly restricted usage of exon V1 in transcripts from mouse gastric tissue. Close sequence homology between exons V1-V10 from mouse rat and human points to a specific functional role rather than a purely structural role for the membrane proximal extracellular domain of the CD44 molecule. PMID- 8509360 TI - Germin, a protein marker of early plant development, is an oxalate oxidase. AB - Germin is a homopentameric glycoprotein, the synthesis of which coincides with the onset of growth in germinating wheat embryos. There have been detailed studies of germin structure, biosynthesis, homology with other proteins, and of its value as a marker of wheat development. Germin isoforms associated with the apoplast have been speculated to have a role in embryo hydration during maturation and germination. Antigenically related isoforms of germin are present during germination in all of the economically important cereals studied, and the amounts of germin-like proteins and coding elements have been found to undergo conspicuous change when salt-tolerant higher plants are subjected to salt stress. In this report, we describe how circumstantial evidence arising from unrelated studies of barley oxalate oxidase and its coding elements have led to definitive evidence that the germin isoform made during wheat germination is an oxalate oxidase. Establishment of links between oxalate degradation, cereal germination, and salt tolerance has significant implications for a broad range of studies related to development and adaptation in higher plants. Roles for germin in cell wall biochemistry and tissue remodeling are discussed, with special emphasis on the generation of hydrogen peroxide during germin-induced oxidation of oxalate. PMID- 8509361 TI - The aleu207-->arg mutation in F1F0-ATP synthase from Escherichia coli. A model for human mitochondrial disease. AB - The mitochondrial ATPase 6 gene encodes a subunit of F1F0 adenosine triphosphate (ATP) synthase. A mutation in the ATPase 6 gene has been genetically linked to two maternally inherited genetic diseases: neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) and certain cases of subacute necrotizing encephalopathy (SNE). Although the severity of both NARP and SNE disease were correlated with the quantity of the ATPase 6leu156-->arg mutation in each patient, the mutation could not be shown to alter F1F0-ATP synthase activity. To investigate the biochemical effects of the ATPase 6leu156-->arg mutation on F1F0 ATP synthase, the aleu207-->arg mutation was constructed in the F1F0-ATP synthase from Escherichia coli to serve as a model for the disease mutation. Characterization of the model bacterial enzyme revealed that the mutation abolishes detectable ATP synthesis via oxidative phosphorylation. The aleu207- >arg mutation results in a structural perturbation blocking proton translocation through F1F0-ATP synthase. The results suggest that a structural defect in human F1F0-ATP synthase is the biochemical basis for NARP and SNE. PMID- 8509362 TI - Substrate inhibition of fibrin-dependent plasminogen activation by tissue-type plasminogen activator. AB - Tissue plasminogen activator (t-PA) is a poor activator of plasminogen, but its catalytic efficiency is greatly enhanced in the presence of fibrin or certain fibrin derivatives. These two very different rates of plasminogen activation provide a basis for the phenomenon of substrate inhibition, which was the subject of the present study. The reaction mixture contained Glu-plasminogen (0-4.0 microM), +/- D-dimer (0.06-1.0 microM), t-PA (0.05-50.0 nM), and S2251 (1.5 mM). Inhibition of the reaction at higher plasminogen concentrations was seen at lower concentrations of t-PA (< 1.0 nM) and D-dimer (< 0.5 microM). The maximum rate of plasminogen activation occurred at 0.2 microM Glu-plasminogen but then decreased progressively above this concentration. At a physiological concentration of plasminogen (2.0 microM), activation was about half that at 0.2 microM. This phenomenon was shown not to be related to Glu-plasminogen aggregation or to a non competitive inhibiting contaminant. Instead, the non-linear Lineweaver-Burk curve in the presence of D-dimer was consistent with substrate inhibition. Increasing the concentration of D-dimer (1.0 microM) and/or t-PA (50 nM) overcame the inhibition and reestablished linearity in the Lineweaver-Burk plots. However, at the higher concentrations of t-PA, the catalytic efficiency was reduced by 50-120 fold, suggesting that t-PA may be less efficient at pharmacological than at physiological concentrations. In conclusion, substrate inhibition in t-PA-induced plasminogen activation is reported for the first time. This phenomenon was confined to low concentrations of t-PA and D-dimer in the presence of physiological concentrations of plasminogen. The observation suggests that small fibrin clots (hemostatic plugs) may be more resistant to t-PA-induced lysis than an occlusive thrombus. PMID- 8509363 TI - Renal vasodilator activity of 5,6-epoxyeicosatrienoic acid depends upon conversion by cyclooxygenase and release of prostaglandins. AB - The 5,6-epoxyeicosatrienoic acid (5,6-EET), a renal vasodilator metabolite of arachidonic acid via cytochrome P450 (P450) requires cyclooxygenase for expression of its vasoactivity as the responses are inhibited by indomethacin and other aspirin-like drugs. We now report on the metabolism of 5,6-EET by rabbit kidneys in order to characterize those metabolites that may account for its vasoactivity. The 5,6-EET was injected close-arterially into the rabbit isolated Krebs-Henseleit perfused kidney, preconstricted with phenylephrine, and the effluent collected throughout the response period. Basal collections, following injection of 100 microliters of vehicle, were made at 20-min intervals before each 5,6-EET injection. Prior to acidic extraction, deuterated 6-keto prostaglandin (PG) F1 alpha and PGE2 were added as internal standards. The extracts were separated by TLC and prostaglandins were derivatized for gas chromatography-mass spectrometry analysis using a negative ion chemical ionization mode. Injection of 0.5, 1, 5, 10, and 20 micrograms of 5,6-EET (n = 4) resulted in dose-related decreases in perfusion pressure of 6 +/- 2, 12 +/- 4, 21 +/- 4, 26 +/- 4, and 27 +/- 7 mm Hg, respectively. Basal perfusates contained 6 keto-PGF1 alpha and PGE2, levels of which were increased by 2-fold or more by 5,6 EET. Perfusates, collected during 5,6-EET administration, also contained 5 hydroxy-PGI1 and 5,6-epoxy-PGE1, cyclooxygenase metabolites of 5,6-EET. This is the first report of the recovery and identification of these 5,6-EET metabolites from an intact organ. Since the responses to 5,6-EET are endothelial-dependent, we also studied the profile of eicosanoids formed following incubation of 5,6-EET with cultured bovine pulmonary endothelial cells. Endothelial cells metabolized 5,6-EET to products with a similar radioactive profile on reverse-phase high pressure liquid chromatography compared to kidney perfusates. We compared the vasodilator activity of 5,6-epoxy-PGE1 and 5-hydroxy-PGI1, chemically synthesized by us from PGE2 and PGF2 alpha, respectively, with PGE2 and PGI2 in the rabbit kidney. The 5,6-epoxy-PGE1 was equipotent to PGE2 as a vasodilator. The ED50 values for 5,6-EET, 5,6-epoxy-PGE1, and PGE2 were 4.69, 0.43, and 0.42 nmol, respectively. Although PGI2 was a potent vasodilator (ED50, 0.24 nmol), 5-hydroxy PGI1 was devoid of activity. Thus, the cyclooxygenase-dependent vasoactivity of 5,6-EET in the rabbit kidney has two components: release of vasodilator prostaglandins, PGE2 and PGI2, and metabolism of 5,6-EET to a prostaglandin analog, 5,6-epoxy-PGE1. PMID- 8509364 TI - Ligninolysis by a purified lignin peroxidase. AB - The lignin peroxidases (LiPs) of white-rot basidiomycetes are generally thought to catalyze the oxidative cleavage of polymeric lignin in vivo. However, direct evidence for such a role has been lacking. In this investigation, 14C- and 13C labeled synthetic lignins were oxidized with a purified isozyme of Phanerochaete chrysosporium LiP. Gel permeation chromatography of the radiolabeled polymers showed that LiP catalyzed their cleavage to give soluble lower-M(r) products. To a lesser extent, the enzyme also polymerized the lignins to give soluble higher M(r) products. This result is attributable to the fact that purified LiP, unlike the intact fungus, provides no mechanism for the removal of lignin fragments that are susceptible to repolymerization. LiP catalysis also gave small quantities of insoluble, perhaps polymerized, lignin, but in lower yield than intact P. chrysosporium does. 13C NMR experiments with 13C-labeled polymer showed that LiP cleaved it between C alpha and C beta of the propyl side chain to give benzylic aldehydes at C alpha, in agreement with the cleavage mechanism hypothesized earlier. The data show that LiP catalysis accounts adequately for the initial steps of ligninolysis by P. chrysosporium in vivo. PMID- 8509365 TI - Structural analysis of the purine repressor, an Escherichia coli DNA-binding protein. AB - The purine repressor protein, PurR, is a member of the lac repressor, LacI, family of Escherichia coli DNA-binding proteins that bind DNA via a highly conserved N-terminal helix-turn-helix motif. Additionally, the members of this family display strong sequence homologies between their larger C-terminal effector binding/oligomerization domains. Analysis of the PurR primary and secondary structures reveals that its C-terminal corepressor binding domain is highly homologous to another group of E. coli-binding proteins, the periplasmic binding proteins, particularly to the ribose-binding protein (RBP). The high resolution x-ray structure of RBP allows this protein to serve as a template with which to model the predicted secondary structure of the corepressor binding domain of PurR. Similarly, the N-terminal DNA binding domain of PurR can be modeled using the NMR-determined structure of the corresponding region (residues 1-56) from LacI as a template. Combining the two, results in a description of the likely secondary structure topology of PurR and implicates residues important for corepressor binding and dimerization. CD spectroscopic studies on PurR, its corepressor binding domain and RBP result in secondary structure estimates nearly identical with those obtained by sequence analyses, thereby providing further corroborating physical evidence for this topological assignment. PMID- 8509366 TI - ATPase-promoting dead end inhibitors of the cAMP-dependent protein kinase. AB - The cAMP-dependent protein kinase is a bifunctional enzyme, catalyzing the phosphorylation of the serine and threonine residues in peptides and proteins (kinase activity) as well as the phosphorylation of water (ATPase activity). We have found that several peptides, which serve as inhibitors of the kinase reaction, will either maintain or enhance the ATPase reaction catalyzed by the enzyme. Positively charged dipeptides (e.g. Arg-Arg), as well as small guanidino containing compounds (e.g. guanethidine) block protein kinase activity yet enhance ATPase activity up to 3.5-fold over that exhibited by the enzyme in the absence of these compounds. In contrast, several nonphosphorylatable peptides, whose primary sequences are based on that of a known substrate (i.e. Leu-Arg-Arg Ala-Ser-Leu-Gly), such as Leu-Arg-Arg-Ala-Ala-Leu-Gly, Leu-Arg-Arg-Ala-Phe-Leu Gly, and Leu-Arg-Arg-Ala-Tyr-Leu-Gly, have little or no effect on the rate of the kinase-catalyzed hydrolysis of ATP. An exception to the latter observation is Leu Arg-Arg-Ala-Cys-Leu-Gly, a cysteine-containing peptide that promotes the protein kinase-catalyzed ATPase reaction by 2.2-fold. We have also found that peptides that possess relatively large amino acid side chain moieties immediately following the arginine dyad (i.e. such as Phe, Tyr, Cys, or Asn at Xaa in Leu-Arg Arg-Xaa-Ala-Leu-Gly) sharply reduce the rate of enzyme-catalyzed ATP hydrolysis. This suggests that in the presence of peptides containing an -Arg-Arg-Ala- sequence, the enzyme-bound gamma-phosphate of ATP is relatively accessible to water. In contrast, when the latter alanine moiety is replaced by a larger residue, access by water to ATP appears to be hindered. These results indicate that certain structural features associated with the substrate or substrate analog have a profound influence on the manner by which these species interact with the protein kinase. Furthermore, the work described herein demonstrates that it is possible to block the physiologically important kinase reaction and simultaneously promote the energetically wasteful ATPase reaction. PMID- 8509367 TI - Cadmium transport across tonoplast of vesicles from oat roots. Evidence for a Cd2+/H+ antiport activity. AB - Cadmium accumulates in the vacuole of plant cells, but the mechanism driving its transport across the vacuole membrane is not understood. Here we present evidence for Cd2+ transport via a Cd2+/H+ antiport activity into tonoplast-enriched vesicles isolated from oat roots. Experimentally, accumulation of Cd2+ into vesicles could be driven by delta pH generated by either V-type ATPase or artificially using nigericin to exchange K+ and H+ in K(+)-loaded vesicles. When tonoplast-enriched vesicles were separated on a linear sucrose gradient, NO3(-) sensitive ATPase, total MgATPase, and delta pH-dependent Cd2+ transport equilibrated at 1.11 g/ml, the density of tonoplast membrane. Cd2+ accumulation in vesicles was accompanied by efflux of protons in a Cd2+ concentration dependent manner characteristic of an antiport activity. The delta pH-dependent Cd2+ accumulation process showed saturation kinetics with a Km(app) of 5.5 microM. Thus the process is a candidate for transport of Cd2+ from the cytoplasm to the vacuolar sap under conditions of low as well as high Cd2+ exposure. PMID- 8509368 TI - Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization. AB - We have reported previously the isolation and preliminary characterization of a 40-kDa cyclosporin A (CsA)-binding protein, cyclophilin-40 (CyP-40). To determine the sequence of this protein, degenerate oligonucleotide primers based on bovine brain CyP-40 tryptic peptides were used to generate a polymerase chain reaction fragment of CyP-40 cDNA. This was used to isolate the complete cDNA from a human pancreatic islet cell library. Northern analysis indicated ubiquitous distribution of CyP-40 mRNA throughout human tissues. The CyP-18 domain of CyP-40 is most similar to maize CyP (64.3% identity), whereas 150 amino acids of the non CyP-18 domain of CyP-40 share 30.7% identity with P59, a member of the steroid receptor complex. Failure to detect glycosylation and mass spectroscopy with isolated CyP-40 indicate minimal, if any, posttranslational modification. Employing a new assay for calcineurin protein phosphatase activity to compare the effects of CyP-40.CsA and CyP-18.CsA complexes, IC50 values of 320 nM +/- 20 and 195 nM +/- 15, respectively, were obtained. A chemical cross-linking study revealed that CyP-40 competes for 125I-CyP-18 binding to calcineurin in the presence of CsA. The homology of CyP-40 to P59 suggests that CyP-40 might be involved in modulating the activity of biologically important receptors. PMID- 8509369 TI - The essential role of tropomyosin in cooperative regulation of smooth muscle thin filament activity by caldesmon. AB - We compared the mechanisms by which caldesmon inhibits actin and actin tropomyosin activation of myosin subfragment 1 (S1) MgATPase activity. Caldesmon always inhibited actin activation by displacing S1.ADP.Pi from actin and inhibition required at least 0.7 caldesmon molecules bond per actin for 90% inhibition. Caldesmon inhibited actin-tropomyosin without any displacement of S1.ADP.Pi; thus it inhibits a rate-limiting step. Inhibition is highly cooperative, requiring no more than one caldesmon bound per 10 actins for 90% inhibition of activation by actin and smooth muscle tropomyosin. The degree of cooperativity is defined by the tropomyosin since inhibition by skeletal tropomyosin requires up to one caldesmon bound per 4 actins for 90% inhibition under identical conditions. Both noncooperative inhibition of actin and cooperative, tropomyosin-dependent, inhibition are manifested by a fragment of caldesmon containing only the C-terminal 99 amino acids (658C), although this fragment does not itself bind to tropomyosin. The functional properties of 658C are very similar to striated muscle troponin I, consequently we propose a similar mechanism for tropomyosin-dependent regulation by caldesmon. Caldesmon binding switches actin-tropomyosin to the "off" or "weak" state and Ca2+/calmodulin binding to caldesmon blocks this switch and thus reactivates the actin filament. PMID- 8509370 TI - 252Cf plasma desorption mass spectrometry applied to the analysis of underivatized rough-type endotoxin preparations. AB - Plasma desorption mass spectrometry has recently been used with success to characterize native, underivatized Re- to Rc-type endotoxins in terms of their constituent lipopolysaccharides. The spectra give masses for the major molecular species of lipopolysaccharide present from which their probable compositions could be inferred using the overall composition determined by chemical analyses. Moreover, the relative intensities of the signals are roughly proportional to the abundance of their corresponding molecular species. Native Rc-, Rb-, and Ra-type enterobacterial endotoxins with 5-10 core sugar units have been rendered amenable to plasma-desorption mass spectrometry analysis by improvement in their solubility and the use of cellobiose as an additive. The spectra of four Salmonella and Escherichia endotoxin preparations demonstrated heterogeneity in acylation and phosphorylation. Since these sources of heterogeneity are critical for many biological activities, the spectra underline the need to define the composition of each preparation of endotoxin used in structure-function studies. PMID- 8509371 TI - The involvement of the arginine 17 residue in the active site of the histidine containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli. AB - Histidine-containing protein, HPr, of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system has an active site His-15 that is phosphorylated to form N delta 1-P-histidine. The nearby conserved residue, Arg-17, has been replaced by: lysine, histidine, glutamate, glycine, serine, and cysteine. All mutations resulted in impairment of the phosphoacceptor function of HPr with enzyme I: kcat/Km values between 6% (Ser-17) and 0.1% (Glu 17), relative to wild type. Several sugar-specific enzymes II had different responses. Both the Vmax and Km of enzyme IIN-acetylglucosamine were altered, while for enzyme IImannose only Km was affected, except for R17E. For both enzymes, kcat/Km values were between 0.5 and 3%, with R17E being 10-fold lower. Except for R17E, minimal effects were observed for enzyme IImannitol. These results suggest that there are different rate-limiting steps in the enzymes II. Phosphohydrolysis properties and the pKa values for His-15 and phosphorylated His 15 determined by NMR for both wild type and mutant HPrs suggest that Arg-17 is partly responsible for the instability of P-His-15 and the depressed pKa values in wild type HPr. Other feature(s) of the tertiary structure influence the protonation of His-15 and the phosphohydrolysis properties of phosphorylated His 15. PMID- 8509372 TI - A specific binding protein from Manduca sexta for the insecticidal toxin of Bacillus thuringiensis subsp. berliner. AB - Biopesticides based on the bacterium Bacillus thuringiensis have attracted wide attention as safe alternatives to chemical pesticides. In this paper, we report, for the first time, the identification and purification of a single binding protein from a lepidopteran insect, Manduca sexta, that is specific for a cryIA toxin of B. thuringiensis. The purified protein appeared as a single band of 210 kDa on a two-dimensional gel, had a pI of approximately 5.5, and stained with Schiff's reagent. The band material was sensitive to proteolytic digestion and was rich with acidic amino acids, indicating its protein nature. Radiolabeled toxin bound to the protein with a Kd value of 708 pM and could be specifically blocked by unlabeled toxin but not by toxins from other subspecies of B. thuringiensis. This study lays the groundwork to clone the toxin binding protein and to determine the molecular mechanism(s) of toxin action. PMID- 8509373 TI - Formation of o-tyrosine and dityrosine in proteins during radiolytic and metal catalyzed oxidation. AB - To evaluate their usefulness as chemical indicators of cumulative oxidative damage to proteins, we studied the kinetics and extent of formation of ortho tyrosine (o-Tyr), dityrosine (DT), and dityrosine-like fluorescence (Ex = 317 nm, Em = 407 nm) in the model proteins RNase and lysozyme exposed to radiolytic and metal-catalyzed (H2O2/Cu2+) oxidation (MCO). Although there were protein dependent differences, o-Tyr, DT, and fluorescence increased coordinately during oxidation of the proteins in both oxidation systems. The contribution of DT to total dityrosine-like fluorescence in oxidized proteins varied from 2-100%, depending on the protein, type of oxidation, and extent of oxidative damage. In proteins exposed to MCO, DT typically accounted for > 50% of the fluorescence at DT wavelengths. These studies indicate that o-Tyr and DT should be useful chemical markers of cumulative exposure of proteins to MCO in vitro and in vivo. PMID- 8509374 TI - Oxidized amino acids in lens protein with age. Measurement of o-tyrosine and dityrosine in the aging human lens. AB - The concentrations of ortho-tyrosine (o-Tyr) and dityrosine (DT) were measured in noncataractous human lenses in order to assess the role of protein oxidation reactions in the aging of lens proteins. The measurements were conducted by selected ion monitoring-gas chromatography/mass spectrometry using deuterium labeled internal standards, which provided both high sensitivity and specificity for the quantitation of o-Tyr and DT. Between ages 1 and 78 years, the o-Tyr concentration in lens proteins varied from 0.3 to 0.9 mmol of o-Tyr/mol of Phe (n = 19), while DT ranged from 1 to 3 mumol of DT/mol of Tyr (n = 30). There were no significant changes in levels of o-Tyr with lens age. There was a statistically significant, but only slight, increase in DT in lens proteins with age (approximately 33% increases between ages 1 and 78, r = 0.5, p < 0.01). At the same time, total protein fluorescence, measured at DT wavelengths (Ex = 317 nm, Em = 407 nm), increased 11-fold between ages 1 and 78 and correlated strongly with age (r = 0.82, p < 0.0001). Although the fluorescence maxima of lens proteins were similar to those of DT, DT accounted for less than 1% of the DT like fluorescence in lens protein at all ages. These observations indicate that oxidation of Phe and Tyr plays a limited role in the normal aging of lens proteins in vivo. PMID- 8509376 TI - Vanadate, a transition state inhibitor of chloroplast CF1-ATPase. AB - The activity of CF1-ATPase was inhibited by vanadate in an allosteric manner with respect to CaATP as substrate. The cooperative interaction was enhanced by preincubation of the enzyme in the presence of ADP and Ca2+ ions and of free divalent metal ions during assay of the activity. The strongest cooperative interaction with a Hill coefficient of 5.3 +/- 0.1 was found when the reaction was stopped after 30 s, before steady state was reached. Under these conditions, the concentration of an exchangeable ADP, tightly bound to one of the active sites on the enzyme, was shown to be the highest. A Ki of 12.4 +/- 1.2 microM for vanadate inhibition was determined under these conditions. Direct measurements with the aid of 51V NMR indicated that vanadate binds to CF1 in the presence of Ca2+ and ADP in a positive cooperative manner with a Hill coefficient of 2.3 +/- 0.2 and an average Kd of 0.3 +/- 0.04 nM. It was suggested that a formation of pentacovalent vanadyl-ADP at the active site caused the inhibition. Vanadyl-ADP was suggested to be a strong inhibitor, being an analogue of a pentacovalent phosphoryl-ADP, which is proposed to be the transition state intermediate of CF1. PMID- 8509375 TI - Sphingosine metabolism induces Ca2+ oscillations in rat pancreatic acinar cells. AB - The possibility that sphingosine or a related metabolite could mediate inositol 1,4,5-triphosphate (1,4,5-IP3)-independent Ca2+ release in pancreatic acinar cells was investigated. In intact rat pancreatic acini superfused at 37 degrees C, sphingosine (10-100 microM) evoked, after a delay of several minutes, an increase in the cytosolic [Ca2+]i which was oscillatory below concentrations of 50 microM. At room temperature no increase in [Ca2+]i was observed. The increase in [Ca2+]i evoked by sphingosine was not inhibited by U73122, and thus was unlikely to be due to phosphatidylinositol (PI) hydrolysis. Furthermore, no PI hydrolysis or 1,4,5-IP3 production was detected on incubation with sphingosine. As metabolism of sphingosine could explain the temperature-dependent action, the effects of sphingosine and related sphingoid bases were tested in permeabilized cells. After a delay of 30 s at 37 degrees C, sphingosine evoked a slow increase in [Ca2+] into the medium. In contrast, addition of sphingosylphosphorylcholine (SPC) resulted in a rapid increase in [Ca2+]. This response was mimicked by 1,4,5 IP3 but not by addition of sphingosine phosphate (1-10 microM), ceramide (30 microM), or sphingomyelin (50 micrograms/ml). SPC appeared to induce release of Ca2+ from the same store as 1,4,5-IP3, as SPC failed to evoke any further increase in Ca2+ from cells previously depleted by addition of a maximal concentration of 2,4,5-IP3 or thapsigargin. 1,4,5-IP3 but not SPC-induced Ca2+ release was blocked by heparin, indicating that SPC-induced Ca2+ release was not mediated through the IP3 receptor-channel complex. This study demonstrates that SPC, a sphingosine metabolite, could be responsible for IP3-independent Ca2+ oscillations previously seen in pancreatic acinar cells. PMID- 8509377 TI - Interferon-gamma priming effects in the activation and deactivation of ISGF3 in K562 cells. AB - ISGF3 is a major protein factor which mediates the transcriptional activation of interferon-inducible genes. ISGF3 is composed of two subunits, ISGF3 gamma and ISGF3 alpha, which are stimulated by interferon-gamma (IFN-gamma) and interferon alpha (IFN-alpha), respectively. In this paper, the effect of pretreatment of IFN gamma on the response of K562 cells to IFN-alpha, termed "gamma-priming," is examined. Using techniques of gene transfection and mobility shift assay, we studied the gamma-priming effects on the kinetics of appearance and disappearance of (i) the protein product of a luciferase reporter gene driven by an IFN inducible promoter and (ii) the binding of ISGF3 to the interferon-stimulated response element. We found that exposure of cells to IFN-gamma prior to IFN-alpha greatly increased both the levels and the rate of ISGF3 binding activity during the early phase of IFN-alpha treatment and caused the amount of ISGF3 bound to the interferon-stimulated response element to decrease more rapidly with time during the later phase. Such effects were reflected also on the kinetics of expression of the interferon-inducible luciferase gene induced by IFN-alpha. In order to understand the basis of these gamma-priming effects, we use an in vitro reconstitution method to examine the kinetics of the subcomponents of ISGF3 in response to different IFN treatments in K562 cells. It was found that gamma priming not only increased the levels of ISGF3 gamma, but it also stimulated both the rates of rise and fall of the activated alpha-component of ISGF3. A molecular model is proposed to explain these findings. PMID- 8509378 TI - Mg2+ inhibits formation of 4Ca(2+)-calmodulin-enzyme complex at lower Ca2+ concentration. 1H and 113Cd NMR studies. AB - Our previous 1H NMR studies indicated that when mastoparan (MP) is added to Ca(2+)-half-saturated calmodulin (2Ca(2+)-CaM) in the absence of Mg2+ ions, Ca2+ ions transfer from the C-terminal-half domain of CaM not interacting with MP to the N-terminal-half domain of CaM interacting with MP at lower MP concentrations (Ohki, S., Yazawa, M., Yagi, K., and Hikichi, K. (1991b) J. Biochem. (Tokyo) 110, 737-742). As a consequence, the active form of 4Ca(2+)-CaM.MP complex is formed. In the present study, we studied the effect of Mg2+ ions on Ca2+ transfer. In the presence of Mg2+ ions, such Ca2+ transfer does not occur. The effects of Mg2+ ions are also studied by observing 113Cd NMR in the presence of M13, the 26 residue peptide of the CaM-binding region of myosin light chain kinase. The 113Cd NMR results show that Mg2+ ions prevent to form the active complex. Mg2+ plays an important role as an inactivating factor to CaM. PMID- 8509379 TI - Structure of the murine Mac-2 gene. Splice variants encode proteins lacking functional signal peptides. AB - The murine Mac-2 gene is composed of six exons dispersed over 10.5 kilobases. S1 nuclease mapping showed multiple transcription initiation sites, clustered within a 30-base pair region. Sequence analysis revealed that a consensus initiator sequence is located in this area which lacks a TATA motif. The untranslated first exon contains an alternative splice donor site, confirming the existence of two cDNA species with the potential to encode proteins differing at their NH2 termini. In vitro expression and translocation experiments demonstrate that both of the alternatively spliced variants of Mac-2 encode proteins which lack a functional signal peptide. Subcellular fractionation studies indicate that most of the Mac-2 protein is present in the cytosol. These results support the view that Mac-2 is exported from the cell by an unusual mechanism which does not depend on the presence of a signal peptide. PMID- 8509380 TI - Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry. AB - It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guerin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2) alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection. PMID- 8509381 TI - Insulin-like growth factor-I regulates transcription of the elastin gene. AB - Neonatal rat aortic smooth muscle cell cultures were used to investigate the mechanisms by which insulin-like growth factor-I (IGF-I) up-regulates aortic elastogenesis. The addition of IGF-I (50 ng/ml) to quiescent smooth muscle cell cultures resulted in a 5-fold increase in the steady-state levels of tropoelastin mRNA beginning between 2 and 4 h and reaching maximal levels at 8 h. Addition of cycloheximide blocked the effect of IGF-I. Nuclear run-on transcription analyses of nuclei isolated from IGF-I-treated cells showed increased synthesis of new tropoelastin transcripts indicating that transcriptional activation is a major component of IGF-I up-regulation. Transient transfections with deletion constructs containing different portions of the elastin 5'-upstream region localized the IGF-I-responsive area to sequences between -195 and -136 base pairs and further showed that this region contains a negative element. Gel retardation assays using nuclear proteins extracted from control and IGF-I-treated cells demonstrated that IGF-I treatment results in the loss of binding complexes. Footprint analyses of specific binding complexes affected by IGF-I show the deprotection of two closely positioned sequences spanning positions -165 to -137 base pairs. These results suggest that IGF-I up-regulation of elastogenesis involves the abrogation of a negative element functionality. PMID- 8509382 TI - Polymorphic regulation of membrane phospholipid composition in Escherichia coli. AB - To investigate whether the phase preference of Escherichia coli membrane lipids is regulated by adjustment of the ratio of bilayer to non-bilayer lipids, the lipid biosynthetic mutant AD93 was used. This strain lacks the ability to synthesize phosphatidylethanolamine, a non-bilayer lipid which normally accounts for 70-80% of the phospholipids in the E. coli membrane. The lack of phosphatidylethanolamine is compensated by a large increase in the levels of phosphatidylglycerol and cardiolipin. This strain has an absolute requirement for high concentrations of divalent cations. Since divalent cations are known to induce HII phase formation in cardiolipin model systems, this suggests that cardiolipin in combination with divalent cations replaces phosphatidylethanolamine in the membrane and that it is the non-bilayer forming property of the latter which is important for membrane functioning. The growth of the mutant strain was found to be dependent on the type and concentration of divalent cations present in the growth medium. In media supplemented with MgCl2 and CaCl2, growth was maximal at concentrations of 30-50 mM. In the presence of SrCl2 a growth optimum was observed at 15 mM. The cells did not grow in the presence of BaCl2 or at high concentrations of SrCl2. Furthermore, this strain was found to adapt the lipid composition of the membrane in reaction to the type of cation present during growth. The phase behavior of dispersions of mutant and parental E. coli derived lipids was studied under a variety of conditions, using 31P NMR. In the presence of the growth-promoting cations at concentrations where there is maximal growth, a bilayer to non-bilayer transition was observed in the lipid dispersions in a narrow temperature range, approximately 10 degrees C above the growth temperature, whereas at concentrations where there is no growth, a bilayer structure was observed at all temperatures tested. This suggests a polymorphic regulation of membrane lipid composition in order to maintain a propensity toward type II structure formation in the membrane. PMID- 8509383 TI - Effect of high pressure on the association of melittin to membranes. AB - To determine the underlying basis for the sensitivity of peripheral peptides to lipid packing, we monitored the change in association of melittin to different membranes under hydrostatic pressure by fluorescence polarization and by fluorescence intensity in the presence of aqueous quenchers. Association to lysophosphatidylcholine micelles or to membranes composed of dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, or dioleoylphosphatidylcholine was found to be stable from 1 to 2000 atm. Similar results were obtained using multilamellar vesicles, small unilamellar vesicles, or large unilamellar vesicles. Thus, the increase in lipid chain packing induced by pressure does not alter the association of bound complexes. This result indicates similar compressibilities of the peptide and the head group binding region. Increasing the ionic strength to increase the charge of the free peptide also resulted in a pressure insensitive complex showing that the hydration does not change upon binding. This conclusion is substantiated by a lack of van't Hoff delta H to dioleoylphosphatidylcholine large unilamellar vesicles. To gain a more molecular picture of these associations, the rotational properties of the tryptophan side chain of bound melittin as a function of lipid packing was also studied. These data indicate subtle differences in peptide orientation in different lipids. PMID- 8509384 TI - Intracellular Ca2+ sequestration and release in intact bovine retinal rod outer segments. Role in inactivation of Na-Ca+K exchange. AB - Intracellular Ca2+ sequestration and Ca2+ release was analyzed in intact rod outer segments (ROS) purified from bovine retinas. Ca2+ influx in Ca(2+)-depleted and fully bleached ROS was mediated exclusively by the Na-Ca+K exchanger and was measured both as a rise in cytosolic free Ca2+ with fluo 3 and as a total transmembrane Ca2+ flux with 45Ca. Ca2+ fluxes across the ROS plasma membrane were not completely reversible, in small part due to inactivation of the Ca2+ extrusion mode of the Na-Ca+K exchanger but mostly due to sequestration of cytosolic Ca2+ into the intradiskal space. Ca2+ release from the intradiskal space into the cytosol could be induced by low concentrations of the Ca2+ ionophore A23187 which gave rise to increases in cytosolic free Ca2+ by several hundred nanomolar (low A23187 concentrations did not affect the Ca2+ permeability of the ROS plasma membrane). We have used intracellular Ca2+ release induced by A23187 to examine inactivation of the rapid Ca2+ efflux mode mediated by the plasma membrane Na-Ca+K exchanger. Inactivation of Na-Ca+K exchange appeared to be dependent on intradiskal Ca2+ as it was abolished by selective Ca2+ permeabilization of the disk membrane by A23187. We discuss possible physiological roles for Ca2+ sequestration and release from ROS disks. PMID- 8509385 TI - Binding of 125I-fasciculin to rat brain acetylcholinesterase. The complex still binds diisopropyl fluorophosphate. AB - Iodination of fasciculin 3 (FAS3) from Dendroaspis viridis venom provided us with a fully active specific probe of fasciculin binding sites on rat brain acetylcholinesterase (AChE). Binding and inhibition are concomitant, as association and inhibition rate constants k1 and ki are identical. The 125I FAS3.AChE complex dissociates very slowly (t 1/2 = 48 h) and is characterized by a dissociation constant, Kd, of 0.4 pM. All the specific binding of 125I-FAS3 to AChE is prevented by FAS3 as from D. angusticeps venom (Kd = 0.4, 14, and 25 pM, respectively). It is also prevented by propidium iodide, BW284C51, and d tubocurarine, which bind to peripheral anionic sites of AChE, by Ca2+ and Mg2+, known to enhance AChE activity through an allosteric phenomenon and by acetylthiocholine concentrations which lead to excess substrate inhibition of the enzyme. Diisopropyl fluorphosphate and paroxon, which inhibit AChE by phosphorylating the catalytic serine, have no effect on either the binding rate or the number of binding sites of 125I-FAS3. O-Ethyl-S2-diisopropylaminoethyl methylphosphonothionate, however, which binds irreversibly to the AChE catalytic site but reversibly to a peripheral site, induces a 130% increase in the binding rate of 125I-FAS3, without changing the total number of 125I-FAS3 binding sites. Our results demonstrate that fasciculins bind on a peripheral site of AChE, distinct from the catalytic site and, at least partly, common with the sites on which some cationic inhibitors and the substrate in excess bind. Since phosphorylation of the catalytic serine (esteratic subsite) by [1,3 3H]diisopropyl fluorophosphate can still occur on the FAS3.AChE complex, the structural modification induced by fasciculins may affect the anionic subsite of AChE catalytic site. PMID- 8509386 TI - Surface-independent acceleration of factor XII activation by zinc ions. I. Kinetic characterization of the metal ion rate enhancement. AB - The effect of zinc ions (Zn(II)) on the activation of factor XII in the absence of a procoagulant surface was investigated by initial velocity kinetic studies at I = 0.15, pH 7.4, and 25 degrees C. Zinc ions at concentrations greater than 160 microM potentiated 99-fold the kcat/KM for the activation of factor XII by kallikrein and, at an optimum concentration of 110 microM, accelerated 140-fold the apparent kcat/KM for factor XII autoactivation. High molecular weight kininogen had no effect on either metal-potentiated reaction. Analysis of the factor XII concentration dependence of initial activation rates revealed that Zn(II), at levels that saturate the effect, accelerates kallikrein activation of factor XII by lowering KM (from 52 to 7.3 microM) and raising kcat (from 2.6 to 31 min-1). For the autocatalytic activation reaction of factor XII in the presence of optimal Zn(II), apparent KM and kcat values of 2.4 microM and 0.041 min-1, respectively, were determined, but these parameters were not resolvable in the absence of the metal ion. Zinc ions minimally affected kallikrein enzymatic activity and inhibited factor XIIa enzymatic activity with KI values of 20-40 microM, suggesting that the rate-enhancing effects of the metal ion are due to interactions with the substrate (factor XII) rather than with the enzyme. The Zn(II) inhibition of factor XIIa enzymatic activity accounted for a decreased Zn(II) enhancement of factor XII autoactivation at high metal ion concentrations (> 110 microM). The Zn(II) concentration dependence of the acceleration of factor XII activation reactions were sigmoid and characterized by Hill coefficients of 3.3-4.3, suggesting that cooperative binding of at least four zinc ions to factor XII was responsible for the Zn(II) potentiating effect. The Zn(II) enhancement of the rates of factor XII activation decreased both above and below pH 7.4 with midpoint pH values of 6.5-7.0 and 8.0, consistent with histidine and possibly water ligands mediating Zn(II) binding to the protein. Despite an apparent weaker binding of Zn(II) to factor XII at pH 6.5, indistinguishable maximum accelerating effects of the metal ion were observed at saturation at this pH, indicating that the increased positive charge of factor XII resulting from protonation at the lower pH did not mimic the effect of Zn(II) binding. These results imply that zinc ions induce a conformational change in factor XII that makes it a better substrate for its enzyme activators. PMID- 8509387 TI - Surface-independent acceleration of factor XII activation by zinc ions. II. Direct binding and fluorescence studies. AB - To determine the role of Zn(II)-factor XII interactions in the rate-enhancing effect of Zn(II) on factor XII activation demonstrated in the preceding paper, equilibrium binding of zinc ions to factor XII, and the spectroscopic changes accompanying this binding were investigated. Equilibrium dialysis provided direct evidence for the binding of Zn(II) to factor XII. The binding data were consistent with 7.8 +/- 0.3 zinc ions binding with an indistinguishable Kd of 91 +/- 6 microM. Binding of Zn(II) was accompanied by a 10% quenching of the intrinsic protein fluorescence and a 2-nm red shift of the wavelength of maximum emission. These spectroscopic changes were specific for factor XII and were not observed with factor XIIa. The Zn(II) concentration dependence of factor XII fluorescence quenching was sigmoid and paralleled the Zn(II)-accelerating effect of factor XII activation by kallikrein and factor XIIa, indicating that the spectral change was reporting Zn(II)-factor XII interactions responsible for the enhanced activation rate. The apparent cooperativity of Zn(II) effects on factor XII fluorescence quenching and activation kinetics, and the apparent noncooperativity in Zn(II) binding to factor XII measured by equilibrium dialysis could be explained by a two-state model in which Zn(II) binding is linked to a conformational change in the protein. The Zn(II)-induced quenching of factor XII fluorescence exhibited a pH dependence consistent with the involvement of histidine residues in the binding of Zn(II). Dynamic quenching of factor XII protein fluorescence by iodide or acrylamide, in the absence and presence of Zn(II), revealed heterogeneity in the environment of the 13 tryptophan residues of factor XII that was markedly reduced by metal ion binding. Together, these results indicate that cooperative interactions of Zn(II) with factor XII induce structural changes in the zymogen that facilitate its proteolytic cleavage and activation. PMID- 8509388 TI - Role of the pseudosubstrate sequence in smooth muscle myosin light chain kinase thermal stability. AB - Smooth muscle myosin light chain kinase (MLCK) is stable in the presence of Ca2+/calmodulin and does not undergo inactivation as reported for skeletal muscle MLCK (Kennelly, P.J., Starovasnik, M.A., Edelman, A.M., and Krebs, E.G. (1990) J. Biol. Chem. 265, 1742-1749). The 61-kDa tryptic fragment of smMLCK-(283-779) with the pseudosubstrate/calmodulin binding sequence deleted undergoes rapid inactivation (t1/2 = 5 min at 25 degrees C). Thermal inactivation renders the 61 kDa fragment more susceptible to cleavage by trypsin. The pseudosubstrate sequence, smMLCK-(787-807) prevents inactivation with high potency (half-maximal protective concentration, PC0.5 = 102 +/- 9 nM). The hexapeptide smMLCK-(797 802), Arg-Arg-Lys-Trp800-Gln-Lys, protected with a similar potency (PC0.5 = 73 +/ 14 nM). The four basic residues as well as Trp were important for maintaining protection by the hexapeptide smMLCK-(797-802). Substitution of Trp800 with Ala or Leu increased the PC0.5 to 500 nM. However, substitution of both aromatic residues Tyr794 and Trp800 in the longer pseudosubstrate peptide-(787-807) had little effect, indicating that with the longer peptide other multiple interactions were sufficient to stabilize the enzyme. The peptide substrate MLC (11-23) A14,15 was also protective (PC0.5 = 380 nM) as was Mg(2+)-ATP, Mg(2+) ADP, and Mg2+ plus adenosine. The results demonstrate that the sequence extending from 787-815 encoding the previously identified overlapping pseudosubstrate and calmodulin binding sequences also contains residues that are essential for maintaining thermal stability but these exhibit distinct structure/function relationships. PMID- 8509389 TI - Rabbit liver microsomal endopeptidase with substrate specificity for processing proproteins is structurally related to rat testes metalloendopeptidase 24.15. AB - The detergent extract of rabbit liver microsomes contains an endopeptidase (MEP) with substrate specificity for peptides containing Arg residues at the P1 and P4 positions in the cleavage site (Kawabata, S., and Davie, E. W. (1992) J. Biol. Chem. 267, 10331-10336). These sequences occur in many proproteins such as the vitamin K-dependent proproteins and prohormones. A cDNA coding for MEP has been obtained from three overlapping clones isolated from two rabbit liver lambda gt10 cDNA libraries. The longest open reading frame of the 3507-base pair cDNA codes for a protein of 704 amino acids, of which 406 residues were confirmed by amino acid sequence analysis. MEP contains a putative active site of -His-Glu-X-X-His-, which is typical of mammalian zinc metallopeptidases. Based on a hydropathy plot, MEP is a hydrophilic protein with no transmembrane domain and no NH2-terminal signal sequence. Amino acid sequence analysis identified Asn at the three potential N-glycosylation sites in the enzyme, indicating that MEP contains no N linked sugar. MEP is homologous with rat testes metalloendopeptidase 24.15 (60% identity), rat mitochondrial intermediate peptidase (24% identity), Escherichia coli dipeptidyl carboxypeptidase (25% identity), and the open reading frame YCL57w present in yeast chromosome III (35% identity). PMID- 8509391 TI - Regulation of metallothionein genes by the ACE1 and AMT1 transcription factors. AB - The AMT1 metalloregulatory trans-acting factor from Candida glabrata was found to functionally mimic the ACE1 metalloregulatory trans-acting factor from Saccharomyces cerevisiae in the copper-induced expression of the chromosomal S. cerevisiae metallothionein gene. Plasmid constructs with promoters of various metal-inducible genes fused to the bacterial beta-galactosidase (lacZ) reporter gene were used in S. cerevisiae to evaluate the roles of ACE1 and AMT1 in mediating metal-stimulated expression. Promoters from the S. cerevisiae CUP1 gene and Cu,Zn-superoxide dismutase (SOD1) and from the C. glabrata MT genes MTI, MTIIa, and MTIIb were used. The ACE1 factor was effective in the metalloregulation of the two S. cerevisiae promoters, CUP1 and SOD1, but of only one C. glabrata promoter, MTI. AMT1 was found to be effective in the metalloregulation of all three C. glabrata MT promoters and the two S. cerevisiae promoters tested. The regulation mediated by both ACE1 and AMT1 was copper dependent and copper-specific. Episomally expressed SWI5, a distinct trans-acting factor of S. cerevisiae, enhanced only the basal expression from promoters. The SWI5 enhancement was not metal dependent. In conclusion, AMT1 and ACE1 are functionally homologous in metal-specific regulation, AMT1 appears to be more promiscuous than ACE1 in this function. PMID- 8509390 TI - The influence of effectors and subunit interactions on Escherichia coli carbamoyl phosphate synthetase studied by differential scanning calorimetry. AB - Differential scanning calorimetry of Escherichia coli carbamoyl-phosphate synthetase and its isolated large and small subunits reveals in each case an irreversible, kinetically controlled transition, at a temperature 14 degrees C higher for the holoenzyme than for the subunits, indicating dramatic stabilization of the subunits in the heterodimer. The deletion of the COOH terminal 171 (mutant CarB'2373) or 385 (mutant CarB2177) residues of the large subunit results in more asymmetric transitions at a temperature 7 degrees C lower than for the wild type. The allosteric effectors IMP, UMP, and ornithine induce small reversible transitions at low temperature in the endotherm for the wild type enzyme, but not for CarB'2373, as expected if the effectors bind in the 171 residue, COOH-terminal region. In contrast, two ligands that bind outside the deleted region, Ap5A (a ligand of both ATP sites) and glycine (an analog of glutamine) decrease and increase, respectively, the stability of the two mutants and of the wild type. The stabilization by glycine requires that the subunits are associated. The results support the implication of the 20-kDa COOH-terminal domain of the large subunit in the allosteric modulation by all the effectors and are consistent with the folding of the large subunit as a pseudohomodimer of its two homologous halves. PMID- 8509392 TI - High affinity binding of the estrogen receptor to a DNA response element does not require homodimer formation or estrogen. AB - We have developed an antibody-based DNA binding assay to study the effects of the absence or presence of an estrogen receptor agonist and two antagonists on the thermodynamic binding parameters for estrogen receptor binding to a consensus estrogen response element in vitro. We first demonstrate that antibodies raised against a region of the estrogen receptor directly adjacent to the DNA-binding domain do not interfere with the receptor's ability to preferentially bind to the vitellogenin estrogen response element in plasmid DNA. Exploiting this property to develop a quantitative DNA binding assay, we demonstrate that estrogen is not required for high affinity binding of the receptor for an oligonucleotide containing this element, nor do antiestrogens alter this interaction. In addition, we find that 1 mol of estrogen receptor is complexed with high affinity to 1 mol of vitellogenin estrogen response element, instead of two estrogen receptors/response element as would be predicted if estrogen receptor homodimer formation was required for high affinity DNA binding. Our data best fit a model in which the active estrogen receptor form is a monomer or heterodimer, but not a homodimer, and the regulatory role of estrogen on the estrogen receptor is the induction of protein-protein, but not protein-DNA, interactions. PMID- 8509393 TI - Suramin induces deoligomerization of human tumor necrosis factor alpha. AB - Suramin inhibits the biological activity of human tumor necrosis factor alpha (TNF) through a direct action on the ligand rather than on its receptors (Grazioli, L., Alzani, R., Ciomei, M., Mariani, M., Restivo, A., Cozzi, E., and Marcucci, F. (1992) Int. J. Immunopharmacol. 14, 637-642). In order to clarify the mechanism whereby suramin leads to inhibition of TNF, we investigated the possibility that suramin might modify the quaternary structure of TNF which is biologically active as a trimer. For this purpose we used a new assay (double streptavidin sandwich assay) designed for the rapid detection of oligomer-monomer conversion of proteins. Taking advantage of this assay we observed, upon incubation with suramin, dissociation of TNF. Suramin-induced dissociation of TNF was confirmed by gel filtration chromatography. Under conditions of partial dissociation, two molecular species were separated. One of higher molecular weight, corresponding to trimeric TNF, was biologically active, whereas the other, corresponding to monomeric TNF, was inactive. These results are at variance with others recently reported, where suramin has been shown to induce microaggregation of several polypeptides (Middaugh, C. R., Mach, H., Burke, C. J., Volkin, D. B., Dabora, J. M., Tsai, P. K., Bruner, M. W., Ryan, J. A., and Marfia, K. E. (1992) Biochemistry 31, 9016-9024). This suggests that suramin inhibits the bioactivity of different protein molecules through opposite effects on their quaternary structure. The present results are, to our knowledge, the first demonstration of a drug inhibiting a target molecule through dissociation of its quaternary structure. PMID- 8509394 TI - Organization and characterization of the rat class 3 aldehyde dehydrogenase gene. AB - Expression of class 3 aldehyde dehydrogenase (ALDH-3) is constitutive or inducible, depending on the tissue. ALDH-3 induction occurs both during neoplastic development and after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to study the regulation of ALDH-3 gene expression, ALDH-3 genomic sequences have been obtained from normal rat genomic DNA. Two overlapping genomic fragments (ALDH-UTR-1 and ALDH-NL2) contain the entire ALDH-3 gene along with considerable 5'- and 3'-flanking sequences. The rat ALDH-3 gene spans approximately 9 kilobases in length and consists of eleven exons; ten coding and one 5'-noncoding. The region 5' to exon one contains several putative transcription factor binding elements which may be important in the TCDD inducibility of this gene. These include a xenobiotic response element (XRE), a drug response element (DRE), LAP and Ap1 binding sites, and one Sp1 site. There are considerable differences in organization between the rat and human class 3 ALDH genes. Primer extension and RNase protection analysis indicate that both basal and TCDD-inducible expression of the ALDH-3 gene utilize the same multiple transcription start sites. PMID- 8509395 TI - In vitro binding of plasma membrane-coated vesicle adaptors to the cytoplasmic domain of lysosomal acid phosphatase. AB - Sorting of the newly synthesized membrane-bound precursor of lysosomal acid phosphatase (LAP) involves internalization from the plasma membrane via clathrin coated pits. Using an in vitro system, we present direct evidence for high affinity interaction of the cytoplasmic domain of LAP with the amino-terminal trunk portion of plasma membrane-coated vesicle adaptors. Coated vesicle adaptors of the trans-Golgi network displayed poor binding to LAP, but high affinity binding to the cytoplasmic tail of the 46-kDa mannose 6-phosphate receptor, which is included in clathrin-coated pits of the trans-Golgi network. Binding of plasma membrane adaptors to the tail peptide of LAP required an internalization signal that contains either tyrosine or phenylalanine. PMID- 8509396 TI - Up-regulation of phospholipase D activity induced by overexpression of protein kinase C-alpha. Studies in intact Swiss/3T3 cells and in detergent-solubilized membranes in vitro. AB - The role of protein kinase C in the mechanism of phospholipase D activation by platelet-derived growth factor and 12-O-tetradecanoylphorbol-13-acetate was studied in Swiss/3T3 fibroblasts that overexpress protein kinase C-alpha. Production of [3H]phosphatidylpropanol (specific product of the phospholipase D catalyzed transphosphatidylation reaction) was determined in cells which were prelabeled with [3H]oleic acid. Accumulation of [3H]phosphatidylpropanol in response to platelet-derived growth factor and 12-O-tetradecanoylphorbol-13 acetate was 2-3-fold greater in protein kinase C-alpha-overexpressing SF1.4 cells compared with the vector control cells, SC1. Basal [3H] phosphatidylpropanol production also was 2-fold higher in SF1.4 cells than in SC1 cells. Hence, -fold stimulation of basal phospholipase D activity by platelet-derived growth factor and 12-O-tetradecanoyl-phorbol-13-acetate was comparable in the two cell lines and was not significantly altered by the overexpression of protein kinase C alpha. Similarly, overexpression of protein kinase C-alpha did not affect either the kinetics of phospholipase D activation nor its dependence on platelet-derived growth factor or 12-O-tetradecanoylphorbol-13-acetate concentration. In vitro assay of phospholipase D activity in membranes isolated from the cells, utilizing exogenous [3H]phosphatidylcholine as a substrate, revealed nearly 2-fold higher phospholipase D activity in SF1.4 cell membranes. Kinetic analysis of detergent solubilized phospholipase D activity indicated that the apparent Vmax and Km of phospholipase D derived from SF1.4 and SF3.2 (protein kinase C-alpha overexpressing) cells are significantly higher than those of phospholipase D from control cells. These results indicate that in Swiss/3T3 cells overexpression of protein kinase C-alpha elevates basal and agonist-stimulated phospholipase D activity in intact cells as well as phospholipase D activity in vitro. These data are consistent with the hypothesis that overexpression of protein kinase C-alpha up-regulates phospholipase D, leading to a constitutive higher level of enzyme activity. Thus, protein kinase C-alpha may play a role in regulating phospholipase D expression. PMID- 8509397 TI - Human interferon-alpha A, -alpha 2, and -alpha 2(Arg) genes in genomic DNA. AB - The frequency in human genomic DNA of three human interferon (IFN) alpha genes which differ from each other by a single base substitution was examined in 11 normal individuals. The polymerase chain reaction (PCR) was used to amplify the coding sequence for the Hu-IFN-alpha 2, Hu-IFN-alpha A, and Hu-IFN-alpha 2(Arg) sequences from genomic DNA. The PCR products were then cloned and individual clones were sequenced. PCR products were also analyzed by restriction endonuclease analysis for the IFN-alpha 2 and IFN-alpha A genes by use of a HinfI site which is eliminated by the substitution of an A for a G in IFN-alpha A. The IFN-alpha A gene which was cloned from the myeloblastoid cell line KG-1 was not observed in any of the 201 clones sequenced from normal individuals or in the Namalwa cell line. It was detected in KG-1 cell genomic DNA where it represented 49% of the clones sequenced. Similarly the IFN-alpha 2(Arg) gene was not detected in normal individuals or in the KG-1 cell line but only in the lymphoblastoid cell line from which it was cloned. In Namalwa cells the IFN-alpha 2(Arg) sequence represented 35% of the clones sequenced while the IFN-alpha 2 sequence comprised 59%. Therefore, both the IFN-alpha A and IFN-alpha 2(Arg) sequences represent alleles of the IFN-alpha 2 gene. PMID- 8509398 TI - Molecular characterization of the in vitro activation of pertussis toxin by ATP. AB - Pertussis toxin (PT)-catalyzed ADP-ribosylation of transducin (Gt) is stimulated by ATP. In the absence of ATP, PT exhibited an approximately 20-fold lower linear velocity than the recombinant S1 subunit (rS1) in catalyzing the ADP-ribosylation of Gt. In the presence of 0.1 mM ATP, the linear velocities of rS1 and PT were essentially identical. ATP increased the kcat of PT-catalyzed ADP-ribosylation of Gt without altering the Kmapp for either Gt or NAD. Further, in the presence of ATP, PT exhibited similar kinetic constants under conditions of variable Gt and variable NAD as rS1 in catalyzing the ADP-ribosylation of Gt. The S1 subunit of PT was cleaved by chymotrypsin to a single immunoreactive peptide in the absence of ATP, while three immunoreactive peptides were generated in the presence of ATP. The S1 subunit of PT was not cleaved by trypsin in the absence of ATP, at the concentrations of trypsin used, while two immunoreactive peptides were produced in the presence of ATP. The immunoreactive peptides produced either by chymotrypsin or trypsin cleavage of the S1 subunit of PT in the presence of ATP were indistinguishable from those produced by cleavage of rS1 with the same protease. Chymotryptic and tryptic cleavage of rS1 was not altered by ATP. When PT was incubated with ATP prior to Bio-Gel P-100 gel filtration, approximately 8% of the S1 subunit dissociated from the B oligomer, as determined by ADP ribosyltransferase assays of the column eluant. This increased to 20% when ATP was included in the column buffer. The presence of dithiothreitol and NAD in addition to ATP did not affect the amount of dissociated S1 subunit. Our data further indicated that activation of PT by ATP was a reversible process. Together, these data showed that ATP quantitatively converted the S1 subunit of PT to a form which was kinetically and conformationally identical with rS1, while only a fraction of the S1 subunit was dissociated from the B oligomer. These results indicate that both S1 subunit which is bound to the B oligomer as well as dissociated S1 subunit are capable of catalyzing the ADP-ribosylation of Gt. PMID- 8509399 TI - Evidence for multiple binding sites for several components of human lymphoblastoid interferon-alpha. AB - The antiproliferative and competitive binding activities of 20 purified components of human lymphoblastoid interferon (IFN)-alpha were compared with that of recombinant human IFN-alpha 2b on Daudi and AU937 cells. We observed broad ranges of antiproliferative activities of the IFN-alpha components on these cell lines. Daudi cells were more sensitive to the IFN-alpha components than AU937 cells; the concentrations of the components that resulted in 50% inhibition of cell growth ranged from 0.003 ng/ml to > 10 ng/ml on Daudi cells and 0.05 ng/ml to > 200 ng/ml on AU937 cells. Component o was the most active human IFN-alpha on both cell lines. Scatchard analysis demonstrated that the number of IFN-alpha 2b binding sites is greater on Daudi cells (12,700 binding sites/cell) than AU937 cells (3,300 binding sites/cell); however, their receptor affinities were similar. Component o, which exhibited high antiproliferative activity on both cell lines, had low affinity for the IFN-alpha 2b binding site on AU937 and Daudi cells. Several human IFN-alpha s (components b', b", and e) appeared to have high affinity binding sites but low antiproliferative activity on both Daudi and AU937 cells. These data suggest that there may be more than one binding site or receptor for human IFN-alpha, and/or there may be a multicomponent receptor involved in the biological actions of these molecules. PMID- 8509400 TI - Cerulenin inhibits the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in brefeldin A-resistant cell lines. AB - We have found that cerulenin, an antibiotic that inhibits de novo fatty acid and cholesterol biosynthesis and fatty acylation of proteins, strongly inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in a brefeldin A (BFA)-resistant mutant of Vero cells (BER-40). The protective effect of cerulenin against ricin was also observed in two other BFA-resistant cell lines, Madin-Darby canine kidney, and PtK1 cells. In contrast to BER-40 cells, no significant effect of cerulenin was observed in Vero cells. Cerulenin did not affect the binding of ricin to the cell-surface receptors, but reduced significantly the internalization of ricin in BER-40 cells; no effect of cerulenin on the binding or internalization of ricin was observed in Vero, PtK1, and Madin-Darby canine kidney cells. Endocytic uptake of fluid-phase markers such as horseradish peroxidase and lucifer yellow was inhibited by cerulenin in BER-40 cells, but the endocytosis of transferrin via the coated pit/coated vesicle pathway was slightly increased. Cerulenin inhibited the degradation and excretion of ricin in BER-40 cells, and this effect of cerulenin was not observed in Vero cells. Furthermore, cerulenin inhibited the bulk protein secretion in a dose dependent manner, with BER-40 cells being more susceptible than Vero cells. These results suggest that in addition to its effect on endocytosis, cerulenin interferes with the intracellular trafficking or processing of toxin molecules, and the vesicle transport system in BER-40 cells appears to be cerulenin sensitive. Since addition of fatty acids and cholesterol did not reverse the effects of cerulenin, the protective effect of cerulenin against protein toxins is not due to an inhibition of de novo fatty acids and cholesterol biosynthesis. PMID- 8509401 TI - Characterization of a novel dentin matrix acidic phosphoprotein. Implications for induction of biomineralization. AB - Acidic phosphorylated proteins have been shown to be prominent constituents of the extracellular matrix of bone and dentin. The acidic phosphoproteins of bone contain more glutamic acid than aspartic acid and a lower serine content than either. On the other hand, the major dentin acidic phosphoproteins, phosphophoryns, have been defined as aspartic acid- and serine-rich proteins, with a lesser content of glutamic acid. Both sets of phosphoproteins have been implicated as key participants in regulating mineralization, but it has been difficult to unify their mechanisms of action. We have now identified, by cDNA cloning, a new serine-rich acidic protein of the dentin matrix, AG1, with a composition intermediate between the bone acidic proteins and dentin phosphophoryns. AG1 has numerous acidic consensus sites for phosphorylation by both casein kinases I and II. Immunochemical and organ culture biosynthetic studies show that AG1 is present in phosphorylated form at low levels in the dentin matrix. If fully phosphorylated, AG1 would bear a net charge of 175/molecule of 473 residues. AG1 contains single RGD integrin binding and N glycosylation sequences. The overall picture that emerges is that of a matrix associated acidic phosphoprotein, with a potentially high calcium ion binding capacity, present at levels compatible with a regulatory role in dentin mineralization. PMID- 8509402 TI - S-100 protein, but not calmodulin, binds to the glial fibrillary acidic protein and inhibits its polymerization in a Ca(2+)-dependent manner. AB - S-100 protein, a Ca(2+)-binding protein of the EF-hand type, interacts with the glial fibrillary acidic protein (GFAP) in a Ca(2+)-dependent manner. The binding of S-100 protein to GFAP was investigated by fluorescence spectroscopy using acrylodan-S-100 protein and cross-linking experiments using the bifunctional cross-linker, disuccinimidyl suberate. The binding affinity was observed to be in the nanomolar range with a stoichiometry of 2 mol of GFAP/mol of S-100 protein (dimer). S-100 protein was found to inhibit the polymerization of GFAP in a dose- and Ca(2+)-dependent manner, with a half-maximal effect at an S-100 protein/GFAP molar ratio of 0.2 and maximal effect at a molar ratio of 0.5. Identical results were obtained irrespective of whether the unfractionated bovine brain S-100 protein mixture (S-100a plus S-100b), S-100ao, S-100a, or S-100b was used. S-100 protein was observed to be maximally effective as an inhibitor of GFAP polymerization at approximately 3 microM free Ca2+. Calmodulin neither bound to GFAP nor inhibited its polymerization. Altogether, the present results suggest that S-100 protein might be involved in the regulation of the state of assembly of glial filaments by binding to and sequestering unpolymerized GFAP. PMID- 8509403 TI - The immunoglobulin-binding protein in vitro autophosphorylation site maps to a threonine within the ATP binding cleft but is not a detectable site of in vivo phosphorylation. AB - In vitro incubation of immunoprecipitated immunoglobulin-binding protein (BiP) complexes with calcium and [gamma-32P]ATP resulted in the phosphorylation of BiP on a threonine residue. This autophosphorylation activity did not occur in the presence of magnesium but had the same pH optimum as reported for its magnesium dependent ATPase activity. This suggested the possibility that both activities could occur through ATP hydrolysis at the same site. In support of this, mutation of either Thr-37 or Thr-229 to a glycine eliminated both autophosphorylation and ATPase activities, and mutation of either residue to a serine significantly reduced both activities. Glutamic acid 175 in HSC71 has been hypothesized to flank the divalent cation complexed with ATP. Mutation of the analogous glutamic acid, Glu-201, in BiP abolished ATPase activity but still supported some autophosphorylation. The in vitro phosphorylation site was mapped to Thr-229 by mutational analysis. This threonine has been hypothesized to interact with the gamma-phosphate of ATP through a polarized water molecule and would be in a position to act as a phosphate acceptor in the ATP hydrolysis reaction. These data imply that both ATPase and autophosphorylation result from ATP hydrolysis at the same site and that the cation associated with BiP determines which activity is observed. Comparison of partial protease digestion or cyanogen bromide cleavage products of in vitro and in vivo phosphorylated BiP demonstrated that Thr-229 is not a detectable site of phosphorylation in cells. Therefore, whatever functional role phosphorylation may have in vivo, it cannot be attributed to autophosphorylation of Thr-229. PMID- 8509404 TI - The putative iron-responsive element in the human erythroid 5-aminolevulinate synthase mRNA mediates translational control. AB - The 52-nucleotide 5'-untranslated region of the human erythroid 5-aminolevulinate synthase mRNA contains a 28-nucleotide iron-responsive element-like stem-loop motif. We fused the 5'-untranslated region upstream to the coding sequence of the human growth hormone cDNA. A chimeric construct containing a mutated variant of the presumptive iron-responsive element was similarly synthesized. Translation of the wild type chimeric transcript was markedly repressed (approximately 95%) in rabbit reticulocyte lysates as opposed to the mutant. Both transcripts translated with comparable efficiency in wheat germ extracts. Purified placental iron regulatory factor selectively and markedly inhibited translation of the wild type chimeric transcript (> 90%) when tested in wheat germ extracts. By contrast, translations of either the mutant chimeric transcript or other control mRNA species were unaffected. The proximal position of the iron-responsive element relative to the cap site was shown to be important for translational control, in vitro. Our studies suggest that interaction of the iron regulatory factor with the iron-responsive element sterically hinders formation of the preinitiation complex, resulting in translational repression. Thus inactivation of the repressor protein by critical levels of iron or heme would trigger translation of this mRNA in erythroid cells. Consequently, protoporphyrin and heme synthesis would be subtly coordinated with iron supply. PMID- 8509405 TI - Hyperglycosylation of hen egg white lysozyme in yeast. AB - The large molecular size of N-glycosylated lysozyme with a polymannose chain was predominantly expressed in the yeast carrying the lysozyme expression plasmid in 9-fold greater secretion compared with the wild type. Complementary DNA encoding hen egg white lysozyme was subjected to site-directed mutagenesis to obtain the Asn-X-Ser/Thr sequence that is the signal for asparagine-linked (N-linked) glycosylation. At positions 49, 67, 70, and 103, the signal for N-linked glycosylation was created. Only the mutant lysozyme whose glycine 49 was substituted with asparagine was expressed in the two types of glycosylated forms, a small oligomannose chain (Man18GlcNAc2)-linked form and a large polymannose chain (Man310GlcNAc2)-linked form, whereas other mutants were not glycosylated. The secreted amount of polymannosyl lysozyme was much higher than that of the oligomannosyl lysozyme. Both types of glycosylated lysozymes were susceptible to endo-beta-N-acetylglucosaminidase cleavage of their carbohydrate chains. The average molecular masses of oligomannosyl and polymannosyl lysozymes were 18 and 71 kDa, respectively. The length of the polymannose chain was found to be 200-350 residues/molecule of lysozyme according to the estimation of the molecular mass distribution by low angle laser light scattering measurements. The protein conformation estimated by CD analysis was completely conserved in these glycosylated lysozymes. The enzymatic activities of oligomannosyl and polymannosyl lysozymes were 100 and 91%, respectively, of wild-type protein when glycol chitin was used as a substrate. In addition, the polymannosyl lysozyme revealed remarkable heat stability in that no coagulation was observed under conditions in which the wild-type lysozyme coagulated. Thus, this novel glycoprotein can be used as a reporter in studies of the processing and sorting of glycoproteins and as a model of the expression of foreign genes in yeast for the construction of stable enzymes. PMID- 8509406 TI - Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes. AB - In the present study, we investigated the mechanisms that regulate apolipoprotein B-100 (apoB) secretion in response to the change of intracellular cholesteryl ester contents by adding low density lipoprotein (LDL) and an inhibitor of 3 hydroxy-3-methylglutaryl-CoA reductase (pravastatin) in rabbit hepatocyte culture system. LDL caused a significant dose-dependent increase in apoB secretion. On the other hand, the addition of pravastatin decreased apoB secretion significantly. LDL caused a dose-dependent increase in cellular cholesteryl ester, while cellular cholesteryl ester was decreased by pravastatin significantly. Therefore, these results indicate that the change of apoB secretion was in parallel with the change of cellular cholesteryl ester contents. Cellular contents of free cholesterol, triglyceride, and phospholipid did not change. To investigate intracellular degradation of apoB prior to secretion, pulse-chase experiments were performed. It was shown that the addition of pravastatin accelerated intracellular degradation of apoB, while LDL slowed the apoB intracellular degradation rate. We also investigated whether the change of cellular cholesteryl ester could affect the apoB mRNA level. Northern blot analysis and solution hybridization RNase protection assay demonstrated that neither LDL nor pravastatin caused a significant change in cellular apoB mRNA level. We conclude that intracellular cholesteryl ester contents play a critical role in apoB secretion, and the intracellular apoB degradation rate could be the main mechanism that regulates apoB secretion in response to the change of intracellular cholesteryl ester level. PMID- 8509407 TI - Peptide-dependent stimulation of the ATPase activity of the molecular chaperone BiP is the result of conversion of oligomers to active monomers. AB - The molecular chaperone BiP purified from bovine liver (bBiP) exhibits a low basal level of ATPase activity that can be stimulated 3-6-fold by synthetic peptides (Flynn, G. C., Chappell, T. G., and Rothman, J. E. (1989) Science 245, 385-390). By contrast, recombinant murine BiP (rBiP) purified to homogeneity following expression in Escherichia coli exhibits a higher basal level of ATPase activity and is much less stimulated by synthetic peptides. Nondenaturing gel electrophoresis showed that rBiP is predominantly monomeric, while bBiP exists in multiple forms probably corresponding to differentially modified monomeric, dimeric, and higher oligomeric species. Some, but not all, synthetic peptides cause conversion of the oligomeric and modified species of bBiP to a monomeric form. We propose that the peptide-dependent ATPase stimulation observed for BiP reflects the conversion of inactive oligomeric and/or modified species into active monomers. PMID- 8509408 TI - Phage and Escherichia coli expression of the human high affinity immunoglobulin E receptor alpha-subunit ectodomain. Domain localization of the IgE-binding site. AB - The high affinity IgE receptor is a multisubunit complex that participates in IgE dependent activation of mast cells and basophils. The IgE-binding portion of the receptor resides exclusively in the alpha-subunit and specifically within the 180 residues of the mature extracytoplasmic portion. In this study the contiguous two domain human alpha-subunit has been displayed on the surface of a filamentous bacteriophage in a form that specifically binds both human and murine IgE but not other isotypes. Phage display of the individual immunoglobulin-like domains reveals that the IgE-binding portion resides exclusively in the COOH-terminal domain and that this domain appears to bind IgE with lower affinity than the comparably displayed two-domain fragment. Phage display results using a chimeric rat-human alpha-subunit fragment suggest that structural elements within the NH2 terminal domain are necessary to impart high affinity IgE binding activity to the alpha-chain ectodomain. The two-domain human receptor fragment was also expressed in a soluble form from Escherichia coli and purified in one step by affinity chromatography. The solution binding of the purified receptor fragment to IgE was measured by fluorescence quench which afforded an approximate equilibrium affinity constant of 2 x 10(9) M-1 together with a stoichiometry of 1 receptor molecule/molecule of IgE. The complementary approach of phage display and E. coli expression used in this study represents a useful strategy for further analysis of discrete receptor epitope(s) that contribute to IgE binding activity. PMID- 8509409 TI - Production and characterization of recombinant heteropolymers of human ferritin H and L chains. AB - Vertebrate ferritins are iron storage proteins composed by 24 subunits of one or more types. The recombinant homopolymers of human ferritin H- and L-type chains differ in iron uptake and in physical stability, but the properties of heteropolymers with various proportions of H- and L-type chains cannot be predicted. Present study shows that unfolded human ferritin H- and L- type chains renature under similar conditions to form homopolymers indistinguishable from the native ones and that, when mixed, the unfolded H and L chains renature to form heteropolymers with restricted heterogeneity and with the expected H:L ratios. Seven of these ferritins with different H:L ratios were analyzed; electrophoretic mobility, immunological reactivity, and stability to guanidine denaturation varied as predicted, based on the homopolymers. In contrast, the rate of iron uptake, monitored by the variation of absorbance at 310 nm, increased in the ferritins that ranged in H chain content from 0 to 35%; further increments in H chains had no additional effect. This finding indicates that, under the present conditions, only a limited number of H chains are needed for the maximum rate of ferritin iron uptake. Variations of L- and H-type chains in vivo may thus have biological relevance. PMID- 8509410 TI - The Saccharomyces cerevisiae VMA6 gene encodes the 36-kDa subunit of the vacuolar H(+)-ATPase membrane sector. AB - The yeast vacuolar membrane proton-translocating ATPase (V-ATPase) is a multisubunit complex comprised of peripheral catalytic, and integral membrane domains. At least eight proteins cofractionate with purified preparations of the enzyme including 100-, 69-, 60-, 42-, 36-, 32-, 27-, and 17-kDa polypeptides (Kane, P.M., Yamashiro, C.T., and Stevens, T.H. (1989a) J. Biol. Chem. 264, 19236 19244). We took a reverse genetic approach to clone the structural gene for the 36-kDa subunit of the V-ATPase, VMA6, vma6 null mutants displayed growth characteristics typical of other vma mutants including sensitivity to media buffered at neutral pH or media containing 100 mM Ca2+. Vacuolar acidification was defective in vma6 cells and isolated vacuolar membrane preparations contained no detectable V-ATPase activity. The VMA6 gene encodes a hydrophilic polypeptide of 345 amino acids (predicted molecular mass 39.8-kDa). We present evidence that the VMA6 gene product (Vma6p) is a non-integral membrane component of the membrane pore domain and is required for V-ATPase complex assembly. Vma6p was removed from wild type vacuolar membranes by strong chaotropic agents such as alkaline Na2CO3 or 5M urea, which did not remove integral membrane polypeptides. In yeast cells lacking the integral membrane portion of the V-ATPase complex, Vma6p was unable to stably associate with vacuolar membranes. Conversely, in mutants specifically lacking Vma6p, components of the V-ATPase integral membrane domain were destabilized, and peripheral subunits failed to assemble onto vacuolar membranes. These results are discussed in the context of a developing model for V-ATPase assembly in yeast. PMID- 8509411 TI - Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU. AB - The mitochondrial histone HM is the major DNA-binding protein in mitochondria and is necessary for maintenance of the mitochondrial genome in the yeast Saccharomyces cerevisiae during growth on fermentable sugars. HM and the Escherichia coli histone-like protein HU have similar activities in vitro, including DNA supercoiling, but share no sequence similarity. We show that HU can functionally complement the respiration deficiency associated with yeast strains lacking HM. Conversely, phenotypes of E. coli cells lacking HU protein, including nucleoid loss and a filamentous cell morphology, were alleviated by expression of HM in these cells. The HU protein of bacteria and the HM protein of mitochondria are therefore functionally complementary in vivo. Functional similarities among HM, HU, and the nuclear HMG1 proteins are implicated and discussed. PMID- 8509412 TI - A region of the C-terminal portion of the human transferrin receptor contains an asparagine-linked glycosylation site critical for receptor structure and function. AB - The transferrin receptor is a cell surface protein and is responsible for the uptake of iron into many eukaryotic cells. In its mature form, the receptor possesses three asparagine-linked oligosaccharides. The effect of asparagine linked glycosylation on the processing and cell surface localization of the human transferrin receptor is examined here by site-directed mutagenesis. Each of the extracellular consensus sequences (Asn-X-Ser/Thr) for asparagine-linked glycosylation was mutated individually and in all possible combinations. The constructs were transfected stably into NIH-3T3 cells and a Chinese hamster ovary cell line lacking endogenous transferrin receptors. Of the seven possible combinations of glycosylation sites, single mutations eliminating glycosylation at either Asn251 or Asn317 do not affect the processing and surface localization of the receptor. Eliminating both of these sites together has a small effect on the behavior of the receptor. However, mutation of the C-terminal glycosylation site (Asn727) has the most profound negative effect on the appearance of the receptor at the cell surface. The mutants lacking glycosylation at Asn727 appear to be retained in the endoplasmic reticulum as an increased association with binding immunoglobulin protein (BiP) is observed. Addition of a new glycosylation site in the C-terminal region of the unglycosylated mutated transferrin receptor restores the cell surface localization and the transferrin binding of the transferrin receptor, indicating that glycosylation in this region is critical for the correct transport of this receptor to the cell surface. PMID- 8509413 TI - Carbohydrate regulation of the rat L-type pyruvate kinase gene requires two nuclear factors: LF-A1 and a member of the c-myc family. AB - Transcription of the L-type pyruvate kinase (L-PK) gene is induced in response to increased carbohydrate metabolism in the liver. We have demonstrated previously that a segment of the 5'-flanking region of the L-PK gene between -183 and -96 is necessary and sufficient for the glucose response in primary hepatocytes. To explore the protein factors that are involved in carbohydrate regulation, we have performed mutational analyses and in vitro binding studies of this segment. Sequences critical for the glucose response were mapped from -171 to -124. This segment contains the consensus binding sites for two nuclear transcription factors: LF-A1 and MLTF. Both factors are capable of binding to the corresponding L-PK sites in vitro. Mutational and functional analyses indicated that LF-A1 is indeed involved in glucose induction of the L-PK gene. The PK MLTF-like site consists of two imperfect CACGTG motifs, the core binding site for a family of transcription factors related to c-myc. Unexpectedly, mutations in either motif that resulted in defective glucose stimulation retained in vitro binding to MLTF. Furthermore, an authentic MLTF binding site from the adenovirus major late promoter was not functionally interchangeable with the natural sequence. These data indicate that binding of MLTF, in presence of LF-A1, is not capable of supporting the glucose response. Conversion of either imperfect motif to CACGTG within the context of the mutations disrupting the opposite site restored the response to elevated glucose. Thus, the factor that recognizes the PK MLTF-like site and participates in mediating the carbohydrate response of the L-PK gene appears to be a member of the c-myc family distinct from MLTF. PMID- 8509414 TI - Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton. AB - Cyclic AMP-dependent protein kinase II beta (PKAII beta) is the principal mediator of cAMP action in neurons. A Kinase Anchor Proteins (AKAPs) are enriched in forebrain neurons and have distinct high affinity binding domains for the regulatory subunit (RII beta) of PKAII beta and components of the dendritic cytoskeleton. The selective accumulation of AKAP.RII beta complexes near dendritic microtubules tethers PKAII beta in proximity with adenylate cyclase in the synaptic plasma membrane and cytoskeletal proteins that are substrates for the kinase, thereby creating intraneuronal target sites for signals carried by cAMP. We have characterized the targeting (anchoring) and tethering (RII beta binding) domains of a prototypic anchor protein AKAP75. Deletion of N-terminal residues 27-48 generated a truncated RII beta-binding protein that partitions equally between the cytosol and detergent-insoluble fractions of HEK293 cells. Further removal of a non-adjacent sequence (residues 77-91) produced a cytosolic protein with unimpaired RII beta binding activity. Thus, two noncontiguous domains mediate the intracellular localization of AKAP75. Boundaries for the RII beta tethering domain were mapped to residues 392-413 by scanning mutagenesis. Residues containing long aliphatic side chains are essential for the high affinity binding of RII beta by AKAP75. Contributions of hydrophobic amino acids to tethering activity also depend on the position of the residue in the sequence. Certain conservative mutations that should not alter significantly the overall hydrophobicity or helicity of the tethering region (e.g. replacement of Leu with Ala) diminish the RII beta binding activity of AKAP75. PMID- 8509415 TI - Topological analysis of quinoprotein glucose dehydrogenase in Escherichia coli and its ubiquinone-binding site. AB - Topological structure of quinoprotein glucose dehydrogenase in the inner membrane of Escherichia coli was determined by constructing protein fusions with alkaline phosphatase or beta-galactosidase. Analysis of the fusions revealed that the dehydrogenase possesses five membrane-spanning segments, and the N-terminal and C terminal portions resided at the cytoplasmic and periplasmic side of the membrane, respectively. These results agreed with the hydropathy profile based on its primary structure. The topological structure suggests that the predicted binding site of the prosthetic group pyrroloquinoline quinone is located at the periplasmic side and that the amino acid residues corresponding to those that were presumed to interact with ubiquinone in one subunit of mitochondrial NADH dehydrogenase also occur at the periplasmic side. When the purified glucose dehydrogenase and cytochrome o ubiquinol oxidase were reconstituted together with ubiquinone into liposomes, a membrane potential could be generated by the electron transfer at the site of the ubiquinol oxidase but not of the dehydrogenase. These results suggest that glucose dehydrogenase has a ubiquinone reacting site close to the periplasmic side of the membrane, and thus its electron transfer to ubiquinone appears to be incapable of forming a proton electrochemical gradient across the inner membrane of E. coli. PMID- 8509416 TI - Subcellular localization of squalene synthase in rat hepatic cells. Biochemical and immunochemical evidence. AB - In the present study we investigated the subcellular localization of squalene synthase (farnesyl-diphosphate:farnesyl-diphosphate farnesyltransferase, EC 2.5.1.21). Squalene synthase catalyzes the formation of squalene from trans farnesyl diphosphate in two distinct steps and is the first committed enzyme for the biosynthesis of cholesterol. Recently, a truncated form of the enzyme from rat hepatocytes was purified, and monospecific antibodies for squalene synthase were produced. This enabled the subcellular localization of squalene synthase by three different methods: (i) analytical subcellular fractionation and measurements of enzyme activities; (ii) immunodeterminations of squalene synthase in the isolated subcellular fractions with a monospecific antibody; and (iii) immunoelectron microscopy. All three methods gave consistent results. The data clearly illustrate that squalene synthase enzymatic activity and squalene synthase are exclusively localized in the endoplasmic reticulum. In rat hepatic peroxisomes we were not able to detect any squalene synthase. In addition, we also demonstrated that squalene synthase in the microsomal fraction is dramatically regulated by a number of hypolipidemic drugs and dietary treatments. PMID- 8509417 TI - Insights into interfacial activation from an open structure of Candida rugosa lipase. AB - The structure of the Candida rugosa lipase determined at 2.06-A resolution reveals a conformation with a solvent-accessible active site. Comparison with the crystal structure of the homologous lipase from Geotrichum candidum, in which the active site is covered by surface loops and is inaccessible from the solvent, shows that the largest structural differences occur in the vicinity of the active site. Three loops in this region differ significantly in conformation, and the interfacial activation of these lipases is likely to be associated with conformational rearrangements of these loops. The "open" structure provides a new image of the substrate binding region and active site access, which is different from that inferred from the structure of the "closed" form of the G. candidum lipase. PMID- 8509418 TI - An insert of seven amino acids confers functional differences between smooth muscle myosins from the intestines and vasculature. AB - The molecular mechanisms underlying the heterogeneity in contractile properties observed among smooth muscle tissues are unknown. We examined whether part of this diversity might be intrinsic to myosin by comparing structural and enzymatic properties of myosins from two physiologically diverse tissues. Using the reverse transcriptase polymerase chain reaction, we compared avian intestinal smooth muscle and vascular smooth muscle myosin heavy chain (MHC) mRNA. We found that intestinal, but not vascular, MHC mRNA contains an insert of 21 nucleotides, encoding 7 amino acids, in a region near the ATP binding site in the myosin head. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of purified myosin revealed that the relative mobilities of the previously described intestinal MHC isoforms SM1 (204 kDa) and SM2 (200 kDa) were slower than the corresponding vascular SM1 and SM2 isoforms. Furthermore, antibodies raised against a synthetic peptide corresponding to the deduced amino acid sequence of the intestinal insert strongly recognized intestinal SM1 and SM2 but only weakly recognized the vascular isoforms. The presence of the insert in intestinal myosin correlated with a higher velocity of movement of actin filaments in vitro and a higher actin-activated Mg(2+)-ATPase activity, compared with vascular myosin. Other than the MHC insert, one other structural difference distinguished intestinal and vascular myosins: two isoforms of the 17-kDa myosin light chain were found in vascular myosin, whereas a single isoform was found in intestinal myosin. Exchange of the intestinal myosin light chains onto the vascular MHC did not alter its activity in the in vitro motility assay, suggesting that the 7 amino acid MHC insert is responsible for the different enzymatic activities of vascular and intestinal myosins. PMID- 8509419 TI - Saccharomyces cerevisiae cytoplasmic tyrosyl-tRNA synthetase gene. Isolation by complementation of a mutant Escherichia coli suppressor tRNA defective in aminoacylation and sequence analysis. AB - Exploiting differences in tRNA recognition between prokaryotic and eukaryotic tyrosyl-tRNA synthetases (TyrRSs), we have isolated the gene for the cytoplasmic TyrRS of Saccharomyces cerevisiae by functional complementation in Escherichia coli of a mutant E. coli tRNA. The tRNA, derived from the E. coli initiator tRNA with changes to allow suppression of amber termination codons, is poorly aminoacylated in E. coli and hence, is only a weak amber suppressor. The same tRNA functions as a good suppressor in S. cerevisiae and is aminoacylated with tyrosine by yeast extracts. We expressed a yeast cDNA library in an E. coli strain carrying the mutant tRNA gene and several genes with amber mutations. cDNA clones were isolated which increased suppression and levels of aminoacylation of the mutant tRNA. Characterization of the gene identified a methionine-initiated open reading frame encoding a protein of 394 amino acids. Expression of this protein in E. coli demonstrated that tyrosine was incorporated during suppression and that yeast cytoplasmic TyrRS activity was produced. Yeast cytoplasmic TyrRS has sequences typical of class I aminoacyl-tRNA synthetases, but only weak overall sequence similarity to the corresponding eubacterial and mitochondrial TyrRSs. However, many of the residues known to line the tyrosyl-adenylate-binding pocket of the Bacillus stearothermophilus enzyme can be aligned in the yeast sequence. These include the aspartic acid and tyrosine residues thought to contact the tyrosine side chain to provide substrate specificity. PMID- 8509420 TI - SII-facilitated transcript cleavage in RNA polymerase II complexes stalled early after initiation occurs in primarily dinucleotide increments. AB - RNA polymerase II ternary complex cleaves its nascent transcript in a 3'-->5' direction in the presence of elongation factor SII (Izban, M. G., and Luse, D. S. (1992) Genes & Dev. 6, 1342-1356; Reines, D. (1992) J. Biol. Chem. 267, 3795 3800). We have characterized the cleavage products generated during the truncation process with a variety of stalled RNA polymerase II ternary complexes containing uniformly labeled transcripts. These complexes, which remain elongation competent, had stopped transcription because one nucleoside triphosphate was missing from the reaction mixture. Using a novel assay system, we demonstrate that cleavage occurs in predominantly dinucleotide increments, liberating 5'-phosphodinucleotides (pNpNs). In one instance with a particular C20 complex, the first cleavage event was equally partitioned between either a di-or trinucleotide increment with all subsequent truncations occurring by the preferred dinucleotide step. Our data indicate that both the kinetics and the exact increment of SII-facilitated transcript cleavage are influenced by transcript sequence. PMID- 8509421 TI - The increment of SII-facilitated transcript cleavage varies dramatically between elongation competent and incompetent RNA polymerase II ternary complexes. AB - Elongation factor SII is required to increase the efficiency of transcription by RNA polymerase II through intrinsic arrest sites. RNA polymerase II ternary complexes exhibit a ribonuclease activity in the presence of SII, truncating nascent transcripts in a 3'-->5' direction. We show here that transcript cleavage is an obligatory step in re-establishing the elongation competency of complexes that have become blocked in elongation at an intrinsic arrest site. SII facilitated transcript cleavage by these arrested complexes released 7-14 nucleotide RNA fragments. In contrast, SII-facilitated transcript cleavage by elongation competent complexes, which are stalled because of the absence of a nucleoside triphosphate from the reaction mixture, occurred primarily in dinucleotide increments. We can partially recreate the arrested phenotype and the preference for the large cleavage increment by stalling ternary complexes such that the 3'-end of the transcript contains consecutive U residues, which mimics the sequence of the 3'-ends of transcripts in arrested complexes. PMID- 8509422 TI - Identification and characterization of a nuclear scaffold protein that binds the matrix attachment region DNA. AB - The association of nuclear DNA with the nuclear matrix (scaffold) is mediated by defined segments of DNA called matrix association region (MAR). By using a plasmid harboring a portion of the Ig kappa gene within which MAR had been located, we searched for proteins recognizing MAR in the nuclear scaffold components electrophoretically separated and blotted onto a membrane. In the presence of nonspecific competitor DNA, the labeled plasmid selectively bound to a protein with apparent molecular weight of 120,000 (designated SP120). The protein was purified directly from SDS-polyacrylamide gels and renatured by a guanidine hydrochloride procedure. The DNA region in the plasmid responsible for the binding to the solubilized SP120 coincided with the 365-base pair HindIII HinfI fragment that had been identified as MAR. In solution, SP120 exhibited a cooperative mode of interaction with the end-labeled MAR fragment. Measurement of relative affinities of MAR subfragments to SP120 showed that the whole region is required for efficient binding. This is consistent with the minimal length for MAR estimated thus far by in situ mapping experiments. The MAR derived from another gene, fushitarazu, also bound specifically to SP120. Immunostaining of whole cells and isolated nuclei with a monoclonal antibody raised against SP120 indicated that the protein is localized in a nuclear skeletal structure. These results suggest the involvement of SP120 in the MAR-mediated anchorage of nuclear DNA to the nuclear scaffold. PMID- 8509423 TI - A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae. AB - We have identified and purified a new DNA binding protein, designated HDF (high affinity DNA-binding factor) from Saccharomyces cerevisiae. HDF binds in a sequence-independent manner to the ends of double-stranded DNA. The protein appears as a stable heterodimer of two polypeptides with molecular masses of 70 and 85 kDa. We have cloned and sequenced the 70-kDa subunit of the HDF protein. The amino acid sequence shows a weak but significant homology with the p70 subunit of the human Ku autoantigen, a protein that also binds to the ends of double-stranded DNA. Hdf- strains generated by one-step gene disruption show a temperature-sensitive phenotype for growth at 37 degrees C. Cells arrest growth at 37 degrees C and after several hours appear as enlarged single-budded cells with abnormally high DNA content indicating a defect in the regulation of DNA replication coupled with or causing a cell cycle arrest in G2 or mitosis. PMID- 8509424 TI - Messenger RNAs expressed in intestine of adult but not baby rabbits. Isolation of cognate cDNAs and characterization of a novel brush border protein with esterase and phospholipase activity. AB - Using a subtractive hybridization method, we have cloned cDNAs corresponding to 10 different mRNAs which share the property of being expressed in the intestine of adult but not baby rabbits. Four could be identified as coding for previously known gene products (sucrase-isomaltase, a glutathione S-transferase, a cytochrome P450, and a long form of ferritin mRNA), while six code for previously unknown proteins. One clone, AdRab-B, codes for a protein of 1458 amino acids, including (i) a putative signal sequence at the NH2 terminus, (ii) four internal repeats, 308-346 amino acids in length, (iii) a hydrophobic stretch near the COOH terminus, which represents a potential membrane anchor, and (iv) a short hydrophilic stretch at the very COOH terminus. The corresponding protein was studied with the aid of antibodies prepared against polypeptides expressed from segments of the cDNA in Escherichia coli. The protein was shown to be proteolytically processed in the intestine (but not when expressed in COS cells) and to be targeted to the brush border membrane of the enterocytes. Finally, the protein was found to have esterase and phospholipase A/lysophospholipase activity. PMID- 8509425 TI - Formation of 19(S)-, 19(R)-, and 18(R)-hydroxyeicosatetraenoic acids by alcohol inducible cytochrome P450 2E1. AB - When reconstituted with cytochrome b5 and NADPH cytochrome P450 oxidoreductase, cytochrome P450 2E1 metabolized lauric, stearic, oleic, linoleic, linolenic, and arachidonic acid to multiple metabolites. Two major metabolites, accounting for 78% of the total metabolism, were produced with arachidonic acid. The Vmax for total metabolite formation from arachidonic acid was 5 nmol/min/nmol P450 with an apparent Km of 62 microM. Gas chromatography-mass spectrometry analysis identified the two major metabolites as monohydroxylated eicosatetraenoic acids (HETEs). The major HETE was 19-hydroxyeicosatetraenoic acid (19-HETE) and comprised 46% of the total metabolite produced. The second metabolite was the omega-2 hydroxylated metabolite (18-HETE) and comprised 32% of the total product formed. Chiral analysis demonstrated that 19-HETE was 70% 19(S)-HETE and 30% 19(R)-HETE. In contrast, 18-HETE was essentially 100% R isomer. Approximately 18% of the total metabolite produced from arachidonic acid coeluted with epoxyeicosatrienoic acid (EET) standards. The EET metabolites were 56.4% 14,15 EET and 43.6% as a mixture of 11,12-EET and 8,9-EET. 5,6-EET was not detected. Anti-P450 2E1 IgG inhibited arachidonic acid metabolism by renal and hepatic microsomes prepared from acetone-treated rabbits. With renal cortex microsomes, the formation of 18-HETE and 19-HETE was inhibited 67 and 25%, respectively, by the antibody. Liver microsomal formation of 18-HETE was inhibited by 87% and 19 HETE by 70%. Thus, under conditions where cytochrome P450 2E1 is induced, the enzyme could contribute significantly to the formation of the omega-1 and omega-2 hydroxylated metabolites of arachidonic acid. PMID- 8509427 TI - Expression of a phosphorylation-resistant eukaryotic initiation factor 2 alpha subunit mitigates heat shock inhibition of protein synthesis. AB - Protein synthesis is dramatically reduced upon exposure of cells to elevated temperature. Concordant with this inhibition, multiple phosphorylation and dephosphorylation reactions occur on specific eukaryotic initiation factors that are required for protein synthesis. Most notably, phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2 alpha) on serine residue 51 occurs. To identify the importance of phosphorylation in control of protein synthesis, we have evaluated the effects of expression of a mutant eIF-2 alpha which is resistant to phosphorylation. Expression of a serine to alanine mutant at residue 51 of eIF-2 alpha partially protected cells from the inhibition of protein synthesis in response to heat treatment. The overexpressed serine to alanine 51 mutant subunit was incorporated into the eIF-2 heterotrimer and was resistant to phosphorylation. These results are consistent with the hypothesis that heat shock inhibition of translation is mediated in part through phosphorylation of eIF-2 alpha. Expression of the wild type or mutant eIF-2 alpha did not affect cell survival or induction of hsp70 mRNA upon heat shock, indicating that although eIF-2 alpha is a heat shock-induced protein, its increased synthesis during heat shock does not alter the heat-shock response. PMID- 8509426 TI - Synthesis and characterization of a new class of inhibitors of membrane associated UDP-glycosyltransferases. AB - A new class of compounds designed to inhibit membrane-associated glycosyltransferases were synthesized and their biological activities were characterized in liver microsomes and human lymphoma cell lines. These inhibitors are composed of N-acyl phenylaminoalcohol derivatives linked to uridine via different spacers. One inhibitor, termed PP36 (5'-[[N-(2-decanoylamino-3-hydroxy 3-phenylpropyloxycarbonyl )-glycyl[amino]-5'-deoxyuridine) competitively inhibited the enzyme glucosyl phosphoryldolichol synthase (Glc-P-Dol synthase) in rat liver microsomes. In rat and human liver microsomes incubated with PP36 and photolabeled with [beta-32P]5-azido-UDP-Glc, Glc-P-Dol synthase was the only protein observed to have decreased photoincorporation. Two other inhibitors, PP37 (5'-O-[[(2-decanoylamino-3-hydroxy-3-phenyl- propyloxycarbonyl)amino]sulfonyl]uridine and PP55 (5'-O-[[(2-decanoylamino-3- phenylpropyloxycarbonyl)amino]sulfonyl]uridine), were also shown to be competitive inhibitors of Glc-P-Dol synthase activity and photolabeling. Activities of glycosyltransferases involved in glycosphingolipid biosynthesis were little affected by these compounds. Analysis of the effects of PP36, PP37, and PP55 on the incorporation of [3H] leucine and [14C]galactose into glycoprotein and glycolipid fractions from two human cell lines indicated the following: PP36 reduced incorporation into both fractions, PP37 was ineffective, and PP55 only decreased incorporation into glycolipids. PMID- 8509428 TI - NADPH inhibits transcription of the Escherichia coli manganese superoxide dismutase gene (sodA) in vitro. AB - We have previously reported that the thiols glutathione, dithiothreitol, and beta mercaptoethanol suppress transcription of the Escherichia coli manganese containing superoxide dismutase gene (sodA) in an in vitro coupled transcription plus translation system (Gardner, P. R., and Fridovich, I. (1987) J. Biol. Chem. 262, 17591-17595). We now report that NADPH, but not NADH, selectively decreases transcription of sodA in vitro and that an NADPH generating system utilizing glucose 6-phosphate and the corresponding dehydrogenase markedly augments this suppressive effect. A redox buffer containing various ratios of oxidized and reduced glutathione also modulated transcription of sodA thus demonstrating the existence of a redox-sensitive mechanism controlling sodA transcription. Fusion of a 120-base pair fragment, containing 90 base pairs of DNA upstream of the sodA transcription initiation site, to a promoterless galactokinase gene (galK) conferred redox-sensitivity to GalK synthesis. We propose that these redox effects act through a redox-sensitive regulator of sodA and that the anabolic reduction charge, [NADPH]/([NADPH]+[NADP+]), is one cellular signal controlling sodA transcription. PMID- 8509429 TI - Primase from Escherichia coli primes single-stranded templates in the absence of single-stranded DNA-binding protein or other auxiliary proteins. Template sequence requirements based on the bacteriophage G4 complementary strand origin and Okazaki fragment initiation sites. AB - We find that neither the hairpins nor bound single-stranded DNA-binding protein (SSB) are required for in vitro primase activity at the G4 complementary strand origin. Primase has the ability to prime synthetic DNA templates in the absence of any auxiliary proteins, including SSB, and in the absence of any DNA secondary structure. primase does, however, initiate primer synthesis starting at a specific nucleotide sequence present in both the G4 origin system and at sites of Okazaki fragment initiation. We tested a series of single-stranded DNA templates that consisted of various portions of the G4 complementary strand origin for the ability to support primer synthesis. Primer synthesis activity was determined using an assay in which primer length and quantity are monitored by the incorporation of [gamma-32P]ATP once per primer and the products analyzed on a denaturing polyacrylamide gel. We find that primase requires only a short DNA template, 5'-(AC)7CTG CAA AGC-3', to synthesize a 17-nucleotide primer starting at the thymidine residue. We also report primase's ability to incorporate dideoxyribonucleotide triphosphates into primers, which has allowed us to determine directly both length and sequence of primers synthesized. PMID- 8509430 TI - Site-directed mutagenesis of the photosystem I reaction center in chloroplasts. The proline-cysteine motif. AB - Site-directed mutagenesis has been used to introduce specific amino acid changes into the photosystem I reaction center in the green alga Chlamydomonas reinhardtii. Plasmids containing mutated copies of the chloroplast psaB gene, encoding a polypeptide of the photosystem I reaction center heterodimer, were introduced into the chloroplast genome by particle bombardment. Successful transformants were selected by two procedures. The first involved complementation of a nonphotosynthetic mutant of Chlamydomonas, CC-2341 (ac-u-g-2.3), which has a frameshift mutation in the psaB gene, and selection of photosynthetic transformants on minimal medium. The second procedure utilized a co transformation procedure with a plasmid containing a rRNA gene that confers spectinomycin resistance. Homologous replacement of the psaB gene was confirmed by screening for a unique restriction enzyme site within the transforming psaB sequences. These procedures have been used to specifically mutate a highly conserved proline-cysteine motif suggested to be important in coordinating the [4Fe-4S] iron-sulfur center Fx. Our results show that the cysteine is essential for assembly of the photosystem I reaction center although the adjacent proline fulfills no identifiable function. The approach described in this paper will be of value to future studies of the structure, function, and assembly of photosystem I. PMID- 8509431 TI - A tightly membrane-associated subpopulation of spectrin is 3H-palmitoylated. AB - A tightly membrane-associated form of spectrin (TMA-spectrin) was labeled when human red blood cells were incubated with [3H]palmitic acid. About 90% of spectrin was not fatty acid-acylated and was extracted from membranes by low salt buffers. The 3H-palmitoylated TMA-spectrin, however, resisted low and even high salt extraction and remained associated with inside-out vesicles that were generated in the process of spectrin-actin extraction from membranes. TMA spectrin was preferentially extracted from KCl-stripped vesicles by 5 M urea at low ionic strength. TMA-spectrin was purified by gel filtration and by ion exchange chromatography in the presence of urea and a non-ionic detergent. Purified TMA-spectrin was 3H-palmitoylated exclusively in the beta subunit to 0.28 mol/mol after a 12-h incubation of red cells. The labeled palmitate may be bound as an ester or thioester, since hydroxylamine (1 M, pH 7.5) released the label completely. Peptide maps of 3H-palmitoylated TMA-spectrin showed three or two labeled peptides from the beta subunit, when generated by V8 protease and trypsin, respectively. Two types of antibodies to spectrin reacted with purified TMA-spectrin, and TMA-spectrin contained the same antigenic peptides as low salt extractable spectrin. Rabbit anti-ankyrin antibodies did not bind to TMA spectrin. The substoichiometric incorporation of [3H]palmitic acid into TMA spectrin could result from the slow turnover of endogenously bound fatty acids. Generation of the tightly membrane-associated and 3H-palmitoylated subpopulation of spectrin cannot be due to entrapment of an unmodified residual fraction of spectrin in right-side-out vesicles. Instead, the data suggest the existence of a subpopulation of spectrin molecules that undergo a covalent fatty acid modification and thereby alter their binding properties. This may offer a new, metabolically dependent mechanism for dynamic interactions between spectrin and the membrane lipid bilayer. PMID- 8509432 TI - The genes of major lysosomal membrane glycoproteins lamp-1 and lamp-2. The 5' flanking sequence of lamp-2 gene and comparison of exon organization in two genes. PMID- 8509433 TI - 8th Meeting of the European Society of Biomechanics. Rome, Italy, 21-24 June 1992. Abstracts. PMID- 8509434 TI - Molecular and cellular features of esophageal cancer cells. AB - More than 70 cell lines were established from esophageal cancer, including 15 TE series cell lines established by the authors. This article reviews molecular and cellular features of esophageal cancer cells from studies using these cell lines as well as primary tumors. The subjects reviewed include primary cultures of normal epithelium of the esophagus and of esophageal tumors, their growth and differentiation properties, chromosomal aberrations, protein kinase C, growth factors and their receptors, oncogenes, and tumor-suppressor genes. Lesions of genetic loci in esophageal cancer include the absence of mutations in ras genes in primary tumors, amplification and overexpression of the c-erbB gene, co amplification of hst-1 and int-2 genes, mutations, and allelic loss of tumor suppressor genes, p53, Rb, APC, and MCC. Future clinical improvement will be achieved on the basis of the understanding of molecular and cellular features of esophageal cancer cells. PMID- 8509435 TI - The EnDA endometrial adenocarcinoma: an oestrogen-sensitive, metastasizing, in vivo tumour model of the rat. AB - A high percentage of endometrial carcinomas contain oestrogen and progesterone receptors. For endocrine therapy of recurrent endometrial carcinoma, only high dose progestins are in clinical use. As, therefore, the development of new endocrine treatment strategies is of great interest, suitable animal models for this tumour are essential. Up to now, only human tumour xenografts transplanted in immune-deficient nude mice, but no syngeneic in vivo tumour models, have been available. In the present article we describe the hormone sensitivity of the EnDA endometrial adenocarcinoma of the DA/Han rat growing as s.c. implants in DA/Han rats and athymic nude mice in serial passage. In both species, the tumour expresses oestrogen, but no progesterone receptors. Transplanted in DA/Han rats or nude mice, ovariectomy reduced tumour weight by 64% and 46% respectively. In both species substitution of ovariectomized animals with oestradiol restored tumour weights to intact control levels. Oestradiol substitution of intact animals did not further enhance tumour growth. The growth of the primary tumour was inhibited by medroxyprogesterone acetate (MPA) at a dose of 100 mg/kg by 67% and by tamoxifen at a dose of 20 mg/kg by 38%. Lung metastases were regularly seen in both species, although to a lesser extent in nude mice than in DA/Han rats. Tamoxifen treatment did not alter the number of lung metastases, whereas MPA or ovariectomy produced a significant reduction in the number of lung metastases. The EnDA endometrial carcinoma of the DA/Han rat with respect to its oestrogen sensitivity, oestrogen receptor expression, morphology and metastatic growth, grossly resembles a typical endometrial adenocarcinoma and can therefore be regarded as a useful in vivo experimental model for the evaluation of new endocrine treatment strategies. PMID- 8509436 TI - Effects of the luteinizing-hormone-releasing hormone (LHRH) antagonist ramorelix (hoe013) and the LHRH agonist buserelin on dimethylbenz[]anthracene-induced mammary carcinoma: studies with slow-release formulations. AB - Luteinizing-hormone-releasing hormone (LHRH) agonists and antagonists are antigonadotropic agents for reversible ovarian/testicular suppression in gynaecology and in oncology. Pituitary inhibition and suppression of the gonadal steroids can be maintained with continuous release rates from biodegradable implants or microparticles. The effects of curative and preventive treatment with slow-release formulations of the LHRH agonist buserelin (implants and microparticles) and the LHRH antagonist ramorelix (hoe013) (microparticles) on dimethylbenz[a]anthracene(DMBA)-induced mammary tumours in rats and the pharmacokinetics of these formulations are described. In addition, direct effects of the LHRH antagonist ramorelix on tumour growth were studied. The release rates of the implants (polylactide-glycolide 75:25) and the microparticles (polylactide glycolide 50:50) were calculated from urinary excretion of the peptides. The curative treatment started at the time of full tumour development (76 days after DMBA induction). A single buserelin implant injection (3.3 mg peptide) resulted in a dramatic tumour regression within 14 days, which was comparable to ovariectomy. It prevented tumour progression for 120 days. Previous studies in rats have shown that ramorelix microparticles (3.6 mg peptide) have a shorter duration of action (about 14 days) in suppression of gonadal function when compared to buserelin microparticles (3.6 mg peptide), where the suppression lasted for about 35 days. As expected, a single injection of ramorelix microparticles (3.6 mg peptide) inhibited tumour progression for only 14 days. This short action is due to a different release profile of the ramorelix microparticles and the different specific activities of peptides incorporated. In the preventive experiments animals were treated 17 days after DMBA induction before tumour development. Treatment with buserelin implants (3.3 mg peptide) every 56 days or with buserelin microparticles (3.6 mg peptide) every 28 days and the treatment with ramorelix microparticles (1.8 mg peptide) every 7 days prevented the development of tumours. Six weeks after the last injection of ramorelix microparticles a strong tumour progression was seen. There was a clear correlation between peptide release and tumour inhibition. The implants and the microparticles were well tolerated, no tissue reaction or side-effects of ramorelix were seen. Treatment of ovariectomized oestradiol-substituted DMBA treated rats resulted in a marginal (not significant) inhibition in tumour development. LHRH antagonists in slow-release formulations (microparticles or implants) represent a new approach in treatment of hormone-dependent tumours because of the immediate onset of gonadal function and the increased drug efficacy due to the controlled release from biodegradable microparticles. PMID- 8509437 TI - Mechanisms of hepatotoxicity caused by dacarbazine in rats. AB - Possible risks of fatal dacarbazine hepatotoxicity have not been studied systematically. We therefore asked whether dacarbazine hepatotoxicity is influenced by the dose or mode of application, by dacarbazine light-decay products, by prior liver damage or by an induction of dacarbazine metabolism. 22 Sprague-Dawley rats were treated with 4.5 mg and 200 mg dacarbazine/kg bodyweight i.p. and i.v., with dacarbazine light-decay products and with 4.5 mg and 200 mg dacarbazine/kg bodymass after previous galactosamine and ethanol treatment. Serum alanine aminotransferase, cholinesterase and white blood cell and platelet numbers were measured and liver histology was evaluated. Dose-dependent dacarbazine hepatotoxicity could be demonstrated by histology. The mode of application, dacarbazine light-decay products and acute liver damage did not influence dacarbazine hepatotoxicity. However 200 mg dacarbazine/kg bodymass after ethanol pretreatment caused significant serological changes and a significant leucodepression. The increased hepato- and myelotoxicity after induction of hepatic microsomal enzymes should be reason to exclude ethanol and drugs that induce hepatic microsomal enzymes prior to treatment with dacarbazine. PMID- 8509438 TI - Acetylsalicylic acid inhibition of n-butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats. AB - We examined the effect of acetylsalicylic acid (ASA) on n-butyl-(4 hydroxybutyl)nitrosamine (BHBN)-induced bladder carcinogenesis in male Wistar rats. Of 29 rats that received 0.05% BHBN in their drinking water for 9 weeks, 8 developed bladder cancer. Only 1 out of 29 rats that received 0.1% ASA in their diet for 20 weeks, including the period of BHBN consumption, developed a tumor. That difference is statistically significant. Bladder weight was significantly higher in rats given BHBN than in controls and in rats given both BHBN and ASA. We conclude that ASA inhibits BHBN-induced bladder carcinogenesis. PMID- 8509439 TI - A, B, H, and Lewis-a and Lewis-b blood group antigens in human breast cancer: correlation with steroid hormone receptor and disease status. AB - Estrogen (ER) and progesterone (PR) hormone receptor status and levels were correlated with blood group antigen (A, B, H, Lewis-a and Lewis-b) expression in 48 cases of human breast cancer. Reduced expression of all the blood group antigens was observed with statistically significant reductions for H, Lewis-a and Lewis-b (P < 0.05). The proportions of ER- and PR-positive breast cancers staining for Lewis-b were greater than in hormone-receptor-negative cancers but the differences were not significant. The loss of Lewis-b antigen in breast cancer increased with tumor grade but did not correlate with axillary lymph node metastases. Loss of Lewis-b antigen is probably not a predictor of local recurrence and survival in the short period of observation. We conclude that the loss of H, Lewis-a and, especially, Lewis-b in breast cancer reflects the invasiveness of breast cancer and that Lewis-a and b expression is probably only marginally and not significantly affected by steroid hormone receptor status and levels. PMID- 8509440 TI - Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue. AB - Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning. PMID- 8509441 TI - Immunological evaluation of patients with invasive carcinoma of the gallbladder. AB - Forty-three patients with invasive adenocarcinoma of the gallbladder were postoperatively studied in order to determine their general immunological status as well as the local immunohistological reaction to the tumor. At the end of the follow-up, they formed two groups: 19 living patients (group GL) and 24 dead patients (group GD). As a control group (GC), 21 patients with cholecystectomy or cholelithiasis and without carcinoma were simultaneously evaluated. In GL, most of the tumors were limited to the gallbladder wall, and in GD, most of the tumors were already disseminated at the time of diagnosis. GD presented a lower percentage of peripheral blood B lymphocytes, as compared to GL and GC cases. Skin tests of delayed hypersensitivity were significantly more reactive in GL cases than in GD cases, and less reactive in GD than in GC cases. The immunohistological evaluation of the gallbladder yielded a lower B lymphocyte infiltration in GD tumors than in the control cases. GL cases showed a higher intratumoral lymphocytic and mononuclear cell infiltration than GD cases. Although the clinical stage was higher in GD than in GL cases, there were also significant differences in the local immune response and the general immunological status. Patients with invasive gallbladder adenocarcinoma showing longer postoperative survival revealed normal or increased local and general immunological reactions, whereas patients with disseminated tumors showed an important humoral and cellular secondary immunodeficiency. PMID- 8509442 TI - Determination of granulocyte/macrophage-colony-stimulating factor secretion by human melanoma cells and its effects on human melanoma cell proliferation. AB - Recently, granulocyte/macrophage-colony-stimulating factor (GM-CSF) became available for overcoming chemotherapy-induced granulocytopenia. GM-CSF not only has a prominent role in the regulation of proliferation and differentiation of haematopoietic cells but it is also secreted by a variety of solid tumours and is capable of exerting growth-stimulatory effects. To evaluate the safety of GM-CSF administration in the treatment of malignant melanoma, we investigated GM-CSF secretion, GM-CSF receptor expression and the effect of GM-CSF on the proliferation of human melanoma cells in vitro. A panel of eight human melanoma cell lines and two fresh tumour specimen was studied. GM-CSF protein was not detectable in culture supernatants by ELISA without stimulation. Interleukin-1 and tumour necrosis factor alpha induced GM-CSF secretion in all four melanoma cell lines tested. When biotinylated GM-CSF was used, the corresponding receptor was not detectable by immunohistochemical or FACScan analysis. The proliferation of eight human melanoma cell lines and two fresh melanoma specimens was determined by the MTT test after 4-6 days of growth in the presence of different concentrations of GM-CSF (0.1-1000 U/ml). Neither proliferation nor growth inhibition was observed. Therefore the effect of GM-CSF on residual tumour cells in vivo may not present a problem during clinical use to stimulate marrow regeneration after or during chemotherapy of metastatic malignant melanoma. PMID- 8509443 TI - A new perspective on microtubules and axon growth. PMID- 8509444 TI - Membrane protein retention in the yeast Golgi apparatus: dipeptidyl aminopeptidase A is retained by a cytoplasmic signal containing aromatic residues. AB - The mechanism by which yeast dipeptidyl aminopeptidase (DPAP) A, type II integral membrane protein, is retained in the late Golgi apparatus has been investigated. Prior work demonstrated that the 118-amino acid cytoplasmic domain is both necessary and sufficient for Golgi retention and that mutant or overexpressed DPAP A no longer retained in the Golgi was delivered directly to the vacuolar membrane (Roberts, C. J., S. F. Nothwehr, and T. H. Stevens. 1992. J. Cell Biol. 119:69-83). Replacement of the DPAP A transmembrane domain with a synthetic hydrophobic sequence did not affect either Golgi retention of DPAP A or vacuolar delivery of the retention-defective form of DPAP A. These results indicate that the DPAP A transmembrane domain is not involved in either Golgi retention or targeting of this membrane protein. A detailed mutational analysis of the cytoplasmic domain of DPAP A indicated that the most important elements for retention were within the eight residue stretch 85-92. A 10-amino acid region from DPAP A (81-90) was sufficient for Golgi retention of alkaline phosphatase, a type II vacuolar membrane protein. Detailed mutational analysis within this 10 amino acid sufficient region demonstrated that a Phe-X-Phe-X-Asp motif was absolutely required for efficient retention. The efficiency of Golgi retention via the DPAP A signal could be diminished by overexpression of wild type but not retention-defective versions of Kex2p, another late Golgi membrane protein, suggesting that multiple Golgi membrane proteins may be retained by a common machinery. These results imply a role for a cytoplasmic signal involving aromatic residues in retention of late Golgi membrane proteins in the yeast Saccharomyces cerevisiae. PMID- 8509445 TI - GLUT-4 NH2 terminus contains a phenylalanine-based targeting motif that regulates intracellular sequestration. AB - Expression of chimeras, composed of portions of two different glucose transporter isoforms (GLUT-1 and GLUT-4), in CHO cells had indicated that the cytoplasmic NH2 terminus of GLUT-4 contains important targeting information that mediates intracellular sequestration of this isoform (Piper, R. C., C. Tai, J. W. Slot, C. S. Hahn, C. M. Rice, H. Huang, D. E. James. 1992. J. Cell Biol. 117:729-743). In the present studies, the amino acid constituents of the GLUT-4 NH2-terminal targeting domain have been identified. GLUT-4 constructs containing NH2-terminal deletions or alanine substitutions within the NH2 terminus were expressed in CHO cells using a Sindbis virus expression system. Deletion of eight amino acids from the GLUT-4 NH2 terminus or substituting alanine for phenylalanine at position 5 in GLUT-4 resulted in a marked accumulation of the transporter at the plasma membrane. Mutations at other amino acids surrounding Phe5 also caused increased cell surface expression of GLUT-4 but not to the same extent as the Phe5 mutation. GLUT-4 was also localized to clathrin lattices and this colocalization was abolished when either the first 13 amino acids were deleted or when Phe5 was changed to alanine. To ascertain whether the targeting information within the GLUT-4 NH2-terminal targeting domain could function independently of the glucose transporter structure this domain was inserted into the cytoplasmic tail of the H1 subunit of the asialoglycoprotein receptor. H1 with the GLUT-4 NH2 terminus was predominantly localized to an intracellular compartment similar to GLUT-4 and was sequestered more from the cell surface than was the wild-type H1 protein. It is concluded that the NH2 terminus of GLUT-4 contains a phenylalanine-based targeting motif that mediates intracellular sequestration at least in part by facilitating interaction of the transporter with endocytic machinery located at the cell surface. PMID- 8509446 TI - Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment. AB - We are studying intercompartmental protein transport to the yeast lysosome-like vacuole with a reconstitution assay using permeabilized spheroplasts that measures, in an ATP and cytosol dependent reaction, vacuolar delivery and proteolytic maturation of the Golgi-modified precursor forms of vacuolar hydrolases like carboxypeptidase Y (CPY). To identify the potential donor compartment in this assay, we used subcellular fractionation procedures that have uncovered a novel membrane-enclosed prevacuolar transport intermediate. Differential centrifugation was used to separate permeabilized spheroplasts into 15K and 150K g membrane pellets. Centrifugation of these pellets to equilibrium on sucrose density gradients separated vacuolar and Golgi complex marker enzymes into light and dense fractions, respectively. When the Golgi-modified precursor form of CPY (p2CPY) was examined (after a 5-min pulse, 30-s chase), as much as 30 40% fractionated with an intermediate density between both the vacuole and the Golgi complex. Pulse-chase labeling and fractionation of membranes indicated that p2CPY in this gradient region had already passed through the Golgi complex, which kinetically ordered it between the Golgi and the vacuole. A mutant CPY protein that lacks a functional vacuolar sorting signal was detected in Golgi fractions but not in the intermediate compartment indicating that this corresponds to a post-sorting compartment. Based on the low transport efficiency of the mutant CPY protein in vitro (decreased by sevenfold), this intermediate organelle most likely represents the donor compartment in our reconstitution assay. This organelle is not likely to be a transport vesicle intermediate because EM analysis indicates enrichment of 250-400 nm compartments and internalization of surface-bound 35S-alpha-factor at 15 degrees C resulted in its apparent cofractionation with wild-type p2CPY, indicating an endosome-like compartment (Singer, B., and H. Reizman. 1990. J. Cell Biol. 110:1911-1922). Fractionation of p2CPY accumulated in the temperature sensitive vps15 mutant revealed that the vps15 transport block did not occur in the endosome-like compartment but rather in the late Golgi complex, presumably the site of CPY sorting. Therefore, as seen in mammalian cells, yeast CPY is sorted away from secretory proteins in the late Golgi and transits to the vacuole via a distinct endosome-like intermediate. PMID- 8509447 TI - Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. AB - A central question in the endocytic process concerns the mechanism for sorting of recycling components (such as transferrin or low density lipoprotein receptors) from lysosomally directed components; membrane-associated molecules including receptors are generally directed towards the recycling pathway while the luminal content of sorting endosomes, consisting of the acid-released ligands, are lysosomally targeted. However, it is not known whether recycling membrane receptors follow bulk membrane flow or if these proteins are actively sorted from lysosomally directed material because of specific protein sequences and/or structural features. Using quantitative fluorescence microscopy we have determined the endocytic route and kinetics of traffic of the bulk carrier, membrane lipids, to address this issue directly. We show that N-[N-(7-nitro-2,1,3 benzoxadiazol-4-yl)-epsilon-aminohexanoyl]- sphingosylphosphorylcholine (C6-NBD SM) in endocytosed as bulk membrane, and it transits the endocytic system kinetically and morphologically identically to fluorescently labeled transferrin in a CHO cell line. With indistinguishable kinetics, the two labeled markers sort from lysosomally destined molecules in peripherally located sorting endosomes, accumulate in a peri-centriolar recycling compartment, and finally exit the cell. Other fluorescently labeled lipids, C6-NBD-phosphatidylcholine and galactosylceramide also traverse the same pathway. The constitutive nature of sorting of bulk membrane towards the recycling pathway and the lysosomal direction of fluid phase implies a geometric basis of sorting. PMID- 8509448 TI - Biogenesis of peroxisomes: isolation and characterization of two distinct peroxisomal populations from normal and regenerating rat liver. AB - According to Poole et al. (1970, J. Cell Biol. 45:408-415), newly synthesized peroxisomal proteins are incorporated uniformly into peroxisomes (PO) of different size classes, suggesting that rat hepatic PO form a homogeneous population. There is however increasing cytochemical and biochemical evidence that PO in rat liver are heterogenous, undergoing significant modulations in shape and size in process of PO morphogenesis (Yamamoto and Fahimi, 1987. J. Cell Biol. 105:713-722). In the present study, the kinetics of incorporation of newly synthesized proteins into distinct PO-subpopulations have been studied using short-term in vivo labeling (5-90 min). Two distinct "heavy" and "light" crude PO fractions were prepared by differential pelleting from normal and regenerating liver, and highly purified PO were subsequently isolated by density-dependent metrizamide gradient centrifugation according to Volkl and Fahimi (1985. Eur. J. Biochem. 149:257-265). The peroxisomal fractions banded at 1.20 and 1.24 g x cm 3. They differed in their mean diameters and form-factors and particularly in respect to the activity of beta-oxidation enzymes which was higher in the "light" PO. Whereas the "light" PO exhibited a single immunoreactive band with the antibody to the 70-kD peroxisomal membrane protein the "heavy" PO contained an additional (68 kD) band. In pulse-labeling experiments "light" PO showed clearly a higher initial rate of incorporation than the "heavy" PO. The relative specific activity in the "heavy" PO fraction, however increased progressively reaching that of "light" PO by 90 min. These observations provide evidence for the existence of different PO populations in rat liver which differ in their morphological and biochemical properties as well as in their rates of incorporation of new proteins. PMID- 8509449 TI - N-formyl peptide receptors in human neutrophils display distinct membrane distribution and lateral mobility when labeled with agonist and antagonist. AB - Receptors for bacterial N-formyl peptides are instrumental for neutrophil chemotactic locomotion and activation at sites of infection. As regulatory mechanisms for signal transduction, both rapid coupling of the occupied receptor to cytoskeletal components, and receptor lateral redistribution, have been suggested (Jesaitis et al., 1986, 1989). To compare the distribution and lateral diffusion of the nonactivated and activated neutrophil N-formyl-peptide receptor, before internalization, we used a new fluorescent N-formyl-peptide receptor antagonist, tertbutyloxycarbonyl-Phe(D)-Leu-Phe(D)-Leu-Phe-OH (Boc-FLFLF, 0.1-1 microM), and the fluorescent receptor agonist formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fnLLFnLYK, 0.1-1 microM). Fluorescent Boc-FLFLF did not elicit an oxidative burst in the neutrophil at 37 degrees C, as assessed by chemiluminescence and reduction of p-nitroblue tetrazolium chloride, but competed efficiently both with formyl-methionyl-leucyl-phenylalanine (fMLF) and fnLLFnLYK. It was not internalized, as evidenced by confocal microscopy and acid elution of surface bound ligand. The lateral mobility characteristics of the neutrophil fMLF receptor were investigated with the technique of FRAP. The diffusion coefficient (D) was similar for antagonist- and agonist-labeled receptors (D approximately 5 x 10(-10) cm2/s), but the fraction of mobile receptors was significantly lower in agonist- compared to antagonist-labeled cells, approximately 40% in contrast to approximately 60%. This reduction in receptor mobile fraction was slightly counteracted, albeit not significantly, by dihydrocytochalasin B (dhcB, 5 microM). To block internalization of agonist-labeled receptors, receptor mobility measurements were done at 14 degrees C. At this temperature, confocal microscopy revealed clustering of receptors in response to agonist binding, compared to a more uniform receptor distribution in antagonist-labeled cells. The pattern of agonist-induced receptor clustering was less apparent after dhcB treatment. To summarize, this work shows that activated N-formyl peptide receptors aggregate and immobilize in the plane of the neutrophil plasma membrane before internalization, a process that is affected, but not significantly reversed, by cytochalasin. The results are consistent with a model where arrested receptors are associated mainly with a cytochalasin-insensitive pool of cytoskeletal elements. PMID- 8509450 TI - A GPI-anchored sea urchin sperm membrane protein containing EGF domains is related to human uromodulin. AB - An Mr 63-kD sea urchin sperm flagellar membrane protein has been previously implicated as a possible receptor for egg jelly ligand(s) that trigger the sperm acrosome reaction (AR). The cDNA and deduced amino acid sequences of the 63-kD protein are presented. The open reading frame codes for a protein of 470 amino acids which contains a putative signal sequence of 25 residues. Western blots using antibodies to two synthetic peptides confirm the sequence to be that of the 63-kD protein. The mRNA is approximately 2,300 bases in length and the gene appears to be single copy. The protein is released from sperm membrane vesicles by treatment with phosphatidylinositol-specific phospholipase C, showing that it is anchored to the flagellar membrane by glycosylphosphatidyl inositol (GPI). Although we cannot demonstrate involvement of the 63-kD protein in the AR, it is of potential interest because it shares significant similarity with the developmentally expressed proteins crumbs, notch and xotch as well as human uromodulin over a region that includes two separate EGF repeats. PMID- 8509452 TI - Proton pumps populate the contractile vacuoles of Dictyostelium amoebae. AB - Amoebae of the eukaryotic microorganism Dictyostelium discoideum were found to contain an interconnected array of tubules and cisternae whose membranes were studded with 15-nm-diameter "pegs." Comparison of the ultrastructure and freeze fracture behavior of these pegs with similar structures found in other cells and tissues indicated that they were the head domains of vacuolar-type proton pumps. Supporting this identification, the pegs were observed to decorate and clump when broken amoebae were exposed to an antiserum against the B subunit of mammalian vacuolar H(+)-ATPase. The appearance of the peg-rich cisternae in quick-frozen amoebae depended on their osmotic environment: under hyperosmotic conditions, the cisternae were flat with many narrow tubular extensions, while under hypo-osmotic conditions the cisternae ranged from bulbous to spherical. In all cases, however, their contents deep etched like pure water. These properties indicated that the interconnected tubules and cisternae comprise the contractile vacuole system of Dictyostelium. Earlier studies had demonstrated that contractile vacuole membranes in Dictyostelium are extremely rich in calmodulin (Zhu, Q., and M. Clarke, 1992, J. Cell Biol. 118: 347-358). Light microscopic immunofluorescence confirmed that antibodies against the vacuolar proton pump colocalized with anti calmodulin antibodies on these organelles. Time-lapse video recording of living amoebae imaged by interference-reflection microscopy, or by fluorescence microscopy after staining contractile vacuole membranes with potential-sensitive styryl dyes, revealed the extent and dynamic interrelationship of the cisternal and tubular elements in Dictyostelium's contractile vacuole system. The high density of proton pumps throughout its membranes suggests that the generation of a proton gradient is likely to be an important factor in the mechanism of fluid accumulation by contractile vacuoles. PMID- 8509451 TI - The cytoplasmic tail of CD44 is required for basolateral localization in epithelial MDCK cells but does not mediate association with the detergent insoluble cytoskeleton of fibroblasts. AB - A number of recent reports on the trafficking of receptor proteins in MDCK epithelial cells have provided evidence that delivery to the basolateral domain requires a specific targeting sequence and that deletion of this sequence results in constitutive expression on the apical surface. To date, these studies have concentrated on receptors which are competent for internalization via the clathrin coated pits. We have examined the localization of a resident plasma membrane protein by transfecting human CD44 into MDCK cells. Using human specific and cross-species reactive antibodies, we show that in MDCK cells both the endogenous and transfected wild-type CD44 are found on the basolateral surface where they are restricted to the lateral domain. Deletion of the CD44 cytoplasmic tail reduces the half life of this mutant protein and causes it to be expressed both on the apical surface and to a significant extent within the cell. We have also used biochemical and morphological analysis to investigate the interaction of CD44 with the cytoskeleton in detergent extracted cells. Strikingly different extraction results were obtained between epithelial and fibroblast cells. However, there is no difference in the Triton X-100 solubility of the transfected wild-type and tail-less CD44 in fibroblasts and both forms of the protein remain associated with the cortical cytoskeleton after Triton X-100 extraction. These results demonstrate that the sequence present in the cytoplasmic domain of CD44 responsible for its distribution in epithelial cells is functionally and spatially separate from the ability of this protein to associate with the cytoskeleton. PMID- 8509454 TI - Cortical and cytoplasmic flow polarity in early embryonic cells of Caenorhabditis elegans. AB - We have examined the cortex of Caenorhabditis elegans eggs during pseudocleavage (PC), a period of the first cell cycle which is important for the generation of asymmetry at first cleavage (Strome, S. 1989. Int. Rev. Cytol. 114: 81-123). We have found that directed, actin dependent, cytoplasmic, and cortical flow occurs during this period coincident with a rearrangement of the cortical actin cytoskeleton (Strome, S. 1986. J. Cell Biol. 103: 2241-2252). The flow velocity (4-7 microns/min) is similar to previously determined particle movements driven by cortical actin flows in motile cells. We show that directed flows occur in one of the daughters of the first division that itself divides asymmetrically, but not in its sister that divides symmetrically. The cortical and cytoplasmic events of PC can be mimicked in other cells during cytokinesis by displacing the mitotic apparatus with the microtubule polymerization inhibitor nocodazole. In all cases, the polarity of the resulting cortical and cytoplasmic flows correlates with the position of the attenuated mitotic spindle formed. These cortical flows are also accompanied by a change in the distribution of the cortical actin network. The polarity of this redistribution is similarly correlated with the location of the attenuated spindle. These observations suggest a mechanism for generating polarized flows of cytoplasmic and cortical material during embryonic cleavages. We present a model for the events of PC and suggest how the poles of the mitotic spindle mediate the formation of the contractile ring during cytokinesis in C. elegans. PMID- 8509453 TI - Evidence for the selective association of a subpopulation of GPIIb-IIIa with the actin cytoskeletons of thrombin-activated platelets. AB - Activation of blood platelets triggers a series of responses leading to the formation and retraction of blood clots. Among these responses is the establishment of integrin-mediated transmembrane connections between extracellular matrix components and the actin cytoskeleton of the platelet. Here we report that a specific subpopulation of the major platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa) (also referred to as alpha IIb beta 3 integrin), becomes incorporated into the detergent-insoluble actin cytoskeleton of platelets during the platelet activation response. The cytoskeletal association of GPIIb-IIIa is independent of platelet aggregation and fibrin sedimentation and is sensitive to cytochalasin D treatment. As determined by Western immunoblot analysis, approximately 22% of the total cellular GPIIb-IIIa becomes associated with the actin cytoskeleton upon thrombin activation in a manner that is independent of the detection of talin, alpha-actinin, or vinculin in the complex. We found that the cytoskeleton-associated GPIIb-IIIa is derived from an intracellular source since it is not available for lactoperoxidase catalyzed radioiodination before platelet activation. Two intracellular sources of GPIIb-IIIa are present in resting platelets: GPIIb-IIIa associated with the alpha-granule secretory compartment as well as surface-inaccessible domains of the surface-connected canalicular system. Interestingly, alpha-granule secretion, which occurs in thrombin-activated platelets and results in the translocation of intracellular GPIIb-IIIa to the plasma membrane, appears to be required for the cytoskeleton incorporation of GPIIb-IIIa that we observe. Collectively, our data provide evidence that a subpopulation of GPIIb-IIIa derived from an intracellular source is selectively linked to the actin cytoskeleton of platelets upon thrombin activation in the absence of platelet aggregation. PMID- 8509455 TI - Porters versus rowers: a unified stochastic model of motor proteins. AB - We present a general phenomenological theory for chemical to mechanical energy transduction by motor enzymes which is based on the classical "tight-coupling" mechanism. The associated minimal stochastic model takes explicitly into account both ATP hydrolysis and thermal noise effects. It provides expressions for the hydrolysis rate and the sliding velocity, as functions of the ATP concentration and the number of motor enzymes. It explains in a unified way many results of recent in vitro motility assays. More importantly, the theory provides a natural classification scheme for the motors: it correlates the biochemical and mechanical differences between "porters" such as cellular kinesins or dyneins, and "rowers" such as muscular myosins or flagellar dyneins. PMID- 8509456 TI - Cytoskeletal remodeling during growth cone-target interactions. AB - Reorganization of the cytoskeleton of neuronal growth cones in response to environmental cues underlies the process of axonal guidance. Most previous studies addressing cytoskeletal changes during growth cone pathfinding have focused on the dynamics of a single cytoskeletal component. We report here an investigation of homophilic growth cone-target interactions between Aplysia bag cell neurons using digitally enhanced video microscopy, which addresses dynamic interactions between actin filaments and microtubules. After physical contact of a growth cone with a physiological target, mechanical coupling occurred after a delay; and then the growth cone exerted forces on and displaced the target object. Subsequent to coupling, F-actin accumulation was observed at the target contact zone, followed by preferential microtubule extension to the same site. After successful target interactions, growth cones typically moved off highly adhesive poly-L-lysine substrates into native target cell surfaces. These events were associated with modulation of both the direction and rate of neurite outgrowth: growth cone migration was typically reoriented to a trajectory along the target interaction axis and rates of advance increased by about one order of magnitude. Directed microtubule movements toward the contact site appeared to be F-actin dependent as target site-specific microtubule extension and bundling could be reversibly randomized by micromolar levels of cytochalasin B in a characteristic manner. Our results suggest that target contacts can induce focal F-actin assembly and reorganization which, in turn, guides target site-directed microtubule redistribution. PMID- 8509457 TI - A role for TGF-beta in oligodendrocyte differentiation. AB - Oligodendrocyte-type-2 astrocyte (O-2A) glial progenitor cells undergo a limited number of mitotic divisions in response to PDGF before differentiating into oligodendrocytes, the myelin-forming cell of the CNS. We examined the mechanism limiting O-2A proliferation, and demonstrate that these cells secrete an inhibitor of cell proliferation that can be neutralized with antibodies to TGF beta. O-2A cells also secrete an inhibitory activity that cannot be neutralized with TGF-beta antibodies. O-2A progenitor cultures express TGF-beta 1 isoform and its transcript, while oligodendrocyte cultures express TGF-beta 1, beta-2, and beta-3 isoforms. Both recombinant TGF-beta 1 and O-2A conditioned medium inhibit the proliferation of O-2A progenitor cells cultured in the presence of PDGF, and this inhibition can be partially neutralized with polyclonal TGF-beta antibodies. Thus, TGF-beta produced by O-2A cells may limit PDGF-driven mitosis and promote oligodendrocyte development. TGF-beta is a less potent inhibitor of O-2A proliferation when these cells are cultured in the presence of bFGF, suggesting that bFGF interferes with TGF-beta signaling. Thus, the production of TGF-beta by cells in the O-2A lineage may account for the distinct effects of PDGF and bFGF on O-2A progenitor cell proliferation. Moreover, our results suggest that TGF beta may be an important mediator of oligodendrocyte differentiation. PMID- 8509460 TI - Evaluating the injured hand. AB - Evaluation of the injured hand is undertaken to assess an acute injury, to diagnose chronic injuries prior to reconstruction, to evaluate function, and to evaluate disability. This article discusses the special evaluation method for each of these categories. PMID- 8509458 TI - The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth. AB - We have previously shown that the neural adhesion molecules L1 and NCAM interact with each other to form a complex which binds more avidly to L1 than L1 to L1 alone (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990a. J. Cell Biol. 110:193-208). This cis-association between L1 and NCAM is carbohydrate-dependent (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990b. J. Cell Biol. 110:209-218). In the present study, we report that L1 and NCAM bind to each other via oligomannosidic carbohydrates expressed by L1, but not by NCAM, as shown in several experiments: (a) complex formation between L1 and NCAM is inhibited by a mAb to oligomannosidic carbohydrates and by the oligosaccharides themselves; (b) NCAM binds to oligomannosidic carbohydrates; (c) within the L1/NCAM complex, the oligomannosidic carbohydrates are hidden from accessibility to a mAb against oligomannosidic carbohydrates; (d) the recombinant protein fragment of NCAM containing the immunoglobulin-like domains and not the fragment containing the fibronectin type III homologous repeats binds to oligomannosidic glycans. Furthermore, the fourth immunoglobulin-like domain of NCAM shows sequence homology with carbohydrate recognition domains of animal C-type lectins and, surprisingly, also with plant lectins. A peptide comprising part of the C-type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM interferes with the association between L1 and NCAM. The functional importance of oligomannosidic glycans at the cell surface was shown for neurite outgrowth in vitro. When neurons from early postnatal mouse cerebellum were maintained on laminin or poly-L-lysine, neurite outgrowth was inhibited by oligomannosidic glycans, by glycopeptides, glycoproteins, or neoglycolipids containing oligomannosidic glycans, but not by nonrelated oligosaccharides or oligosaccharide derivates. Neurite outgrowth was also inhibited by the peptide comprising part of the C-type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM. The combined results suggest that carbohydrate-mediated cis-associations between adhesion molecules at the cell surface modulate their functional properties. PMID- 8509461 TI - Recognizable dysfunction syndromes. AB - Many presentations of dysfunctional postures of the upper extremity have been described in the literature. Attempts have been made to differentiate these situations by describing their physical and pathophysiologic circumstances. Unfortunately, these attempts to define and differentiate the various conditions that are recognizable patterns of upper-extremity dysfunction syndromes have not been entirely successful. This failure is perhaps because hard and firm diagnostic criteria that would specifically delineate each of these circumstances are wanting. At best, it can be said that there are patients who will present with pain as their primary complaint and who present with physical findings that would best support a diagnosis of reflex sympathetic dystrophy. There are others who present with dysfunctional postures in which pain is not a primary presenting complaint. In addition, are those in an intermediate zone, where pain and dysfunction are intermixed, and where prolonged observation may help to place them in one category or the other. Recent evidence has suggested that patients with painless dysfunctional syndrome benefit from the attentions of psychically oriented providers. The timing and appropriateness of such interventions require further study. The literature of the behavioral scientists and that of the practitioners of the medical arts is bereft of concrete explanations for causation and specific definitive solutions. PMID- 8509459 TI - SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway. AB - SPARC (osteonectin/BM40) is a secreted protein that modifies the interaction of cells with extracellular matrix (ECM). When we added SPARC to cultured rabbit synovial fibroblasts and analyzed the secreted proteins, we observed an increase in the expression of three metalloproteinases--collagenase, stromelysin, and the 92-kD gelatinase--that together can degrade both interstitial and basement membrane matrices. We further characterized the regulation of one of these metalloproteinases, collagenase, and showed that both collagenase mRNA and protein are upregulated in fibroblasts treated with SPARC. Experiments with synthetic SPARC peptides indicated that a region in the neutral alpha-helical domain III of the SPARC molecule, which previously had no described function, was involved in the regulation of collagenase expression by SPARC. A sequence in the carboxyl-terminal Ca(2+)-binding domain IV exhibited similar activity, but to a lesser extent. SPARC induced collagenase expression in cells plated on collagen types I, II, III, and V, and vitronectin, but not on collagen type IV. SPARC also increased collagenase expression in fibroblasts plated on ECM produced by smooth muscle cells, but not in fibroblasts plated on a basement membrane-like ECM from Engelbreth-Holm-Swarm sarcoma. Collagenase was induced within 4 h in cells treated with phorbol diesters or plated on fibronectin fragments, but was induced after 8 h in cells treated with SPARC. A number of proteins were transiently secreted by SPARC-treated cells within 6 h of treatment. Conditioned medium that was harvested from cultures 7 h after the addition of SPARC, and depleted of residual SPARC, induced collagenase expression in untreated fibroblasts; thus, part of the regulation of collagenase expression by SPARC appears to be indirect and proceeds through a secreted intermediate. Because the interactions of cells with ECM play an important role in regulation of cell behavior and tissue morphogenesis, these results suggest that molecules like SPARC are important in modulating tissue remodeling and cell-ECM interactions. PMID- 8509462 TI - Psychologic assessment of patients with industrial hand injuries. AB - The benefits and rationale for including a psychologic assessment of a patient with an industrial hand injury are discussed. Issues of compliance and malingering in patients are addressed. The role of pre-existing conditions in understanding an injured patient's current emotional state is explored and contrasted with posttraumatic stress disorders. Recent trends in psychologic assessment techniques are highlighted. PMID- 8509463 TI - Understanding Workers' Compensation Law. AB - "Understanding Workers' Compensation Law" is a primer on workers' compensation, intended to give physicians a basic understanding of how workers' compensation systems function. With this background, it is hoped that those physicians who treat patients suffering from work-related injuries will more fully appreciate their role in the system. The article also outlines a few helpful hints to assist the physician when she or he is treating workers' compensation patients so that the physician can streamline his or her practice and involvement in this area and make interaction with all parties less burdensome. PMID- 8509465 TI - Carpal tunnel syndrome and its relation to general physical condition. AB - Risk for carpal tunnel syndrome is closely related to general physical condition. Our findings confirm that healthy people are less likely to develop median nerve conduction abnormalities at the carpal tunnel than are unhealthy people. Being overweight, older, and physically inactive are major risk factors for slowing and clinical CTS. Workers' compensation patients with CTS, as a group, are identifiable by being overweight and physically inactive. Individual factors, such as body mass index, age, wrist dimensions, and physical activity, are far more important for determining who develops clinical CTS than are job-related factors, such as specific job, force or repetitions, duration of employment, or industry. PMID- 8509464 TI - Patterns of carpal tunnel syndrome. AB - Patterns of carpal tunnel syndrome have been presented, each with characteristic history and physical examination findings. Overlap is common; however, a prominent pattern can usually be identified to recommend primary treatment. The cumulative trauma patterns of tenosynovitis and position can be controlled in about two thirds of cases by nonsurgical management. The other major cumulative trauma pattern, vibration, usually requires avoidance, which commonly involves a job change. The lumbrical pattern responds to surgery with special attention to complete distal release of the transverse carpal ligament. External pressure from tool use requires design modification. Anatomic variations due to arthritis, tumors, or trauma are contraindications for the endoscopic techniques. PMID- 8509466 TI - Ergonomics for the upper extremity. AB - "Ergonomics for the Upper Extremity" provides a medical analysis framework integrated into ergonomic redesign concepts. Within the ergonomic redesign discussion, general design guidelines and standards are presented. For example, ergonomic stress on the wrist is discussed as it relates to arm function. Then, ergonomic design changes are introduced. PMID- 8509467 TI - Ergonomic hand tool design. AB - The use of ergonomic design and appropriate selection of hand tools can reduce exposure to cumulative trauma. The design and principles presented in this article should help reduce the biomechanical stresses to the workers' hands, arms, and shoulders. Remember, tissues of each individual have a threshold of resistance, and if that threshold is crossed too many times by a defective or ill fitting tool, pathologic changes can occur. The proper tool design, rotating work schedules, work pacing, scheduling, and exercise programs can, in combination, improve productivity and promote human wellness. PMID- 8509469 TI - Vibration white finger. AB - Vibration white finger is a form of secondary Raynaud's phenomenon caused by vibratory hand tools. The pathophysiology is multifactorial, with involvement of the peripheral vascular system, sensory receptors, peripheral nerves, muscles, bones, and joints. The diagnosis of this condition is essentially clinical. In this article, the pathophysiology, clinical presentation, diagnosis, industrial standards of exposure, preventive measures, and treatment modalities have been reviewed. PMID- 8509468 TI - The burned hand. AB - Like other work-related injuries, the performance and documentation of a thorough history and physical examination will allow optimal care of the burned worker by accepted management methods. Through understanding of the physical properties of electricity and improving understanding of the pathophysiology of the electric injury, state-of-the-art surgical reconstruction can be appropriately applied. The diversity of chemical compounds at the work place and the wide variety of early measures advocated for treatment requires prevention of chemical burns and careful on-site documentation of chemicals and availability of first aid measures. PMID- 8509470 TI - The nurse's evaluation of cumulative trauma. AB - The role of the nurse is valuable in laying the groundwork for the assessment of the patient with numbness, tingling, and/or upper extremity pain. Through the initial history the nurse can establish rapport with the patient and provide a good chronology of the problem. This can assist the physician with the physical examination. PMID- 8509471 TI - A practical guide to diagnostic imaging of the upper extremity. AB - Imaging of the upper extremities can be challenging and rewarding. Newer imaging modalities, including MRI and CT, have greatly expanded the ability of the radiologist to define soft-tissue abnormalities in the wrist, especially triangular fibrocartilage tears and carpal and radioulnar instability. MRI of the shoulder has almost replaced the arthrogram for diagnosing rotator cuff tears. The plain film, however, remains the mainstay of bone imaging and is the most efficacious first step in the diagnostic work-up. The radionuclide scan, although nonspecific, may provide a map for the radiologist to locate occult lesions. Dialogue between the surgeon and radiologist is essential to effective upper extremity evaluations. The radiologist can maximize his or her effectiveness by performing a brief history and physical examination of the patient. PMID- 8509472 TI - Fractures of the hand and wrist. AB - The management of fractures from the industrial setting is very similar to treatment of fractures that occur elsewhere. However, the surgeon must constantly be on guard for any associated injuries that may be unique to the workplace, such as exposure to heat, cold, chemicals, or electricity. An accurate medical history of the patient and etiology of the injury are necessary. The overall emphasis must be a return to gainful employment. Treatment should be managed from the beginning. The initial action should be an aggressive approach, whether management is conservative or surgical, with a minimum of secondary procedures. An active role by the physician and his or her staff, and especially that of the hand therapist, should emphasize to the employer the advantages of returning the patient to work as soon as possible. PMID- 8509473 TI - What the hand surgeon should know about workers' compensation. AB - It is important for surgeons treating work-related conditions to be knowledgeable of workers' compensation laws in their states. They should also work closely with the designated provider and/or employer to effect speedy recovery and return to work. PMID- 8509474 TI - Managed care and workers' compensation. AB - This article defines the workers' compensation system, including injury statistics and reasons for spiraling costs and suggests to employers ways to manage this risk in an effort to achieve both employee satisfaction and decreased financial liability. As key components of the system, physicians are educated as to how the system works and encouraged to become active participants in helping promote employee well-being. PMID- 8509475 TI - Chronic urinary tract infections in elderly patients. PMID- 8509476 TI - Oncogenes and tumor suppressor genes. AB - Molecular oncologists are elucidating the genetic mechanisms by which cancer cells proliferate. Prominent examples among dominant oncogenes include members of the ras family, which are activated by point mutations that perpetuate transduction of growth signals. The best-studied tumor suppressor gene is p53, which appears to be involved in the repair of damaged DNA. PMID- 8509477 TI - Tamoxifen in breast cancer. PMID- 8509479 TI - The virtual world. PMID- 8509478 TI - The interested doctor. PMID- 8509480 TI - Effective management of penetrating abdominal trauma. PMID- 8509481 TI - Alcohol hypoglycemia. PMID- 8509482 TI - A systematic approach to disorders of the cervical spine. AB - Pain in the neck may arise from a clear-cut cause (e.g., an auto accident) or without warning or apparent reason. It may limit exercise, preclude driving, or interfere with sleep, and at its worst make any movement excruciating. Common denominators are rare, although age is often a fundamental factor. It is usually best to begin management conservatively. PMID- 8509483 TI - An undiagnosed pleural effusion. PMID- 8509484 TI - The psychopathology of everyday driving. PMID- 8509485 TI - Health care reform at $2 a pack. PMID- 8509486 TI - Syncope in a young woman with chronic back pain. PMID- 8509487 TI - Facial lesions in an art student with a history of herpes. PMID- 8509488 TI - Procainamide-induced lupus in the elderly. AB - The usual aids to diagnosis--such as symptoms and antinuclear antibodies--do not reliably distinguish this important entity from idiopathic SLE. Age, sex, and antibody type are often clues, but in some cases, only time and clinical course will tell. PMID- 8509489 TI - Annotation: methodological and conceptual issues in research on childhood resilience. PMID- 8509490 TI - The natural history of change in intellectual performance: who changes? How much? Is it meaningful? AB - A prerequisite step for studying the magnitude and meaning of IQ change is to distinguish between true IQ change that is a researchable phenomenon and IQ "change" that can be accounted for by measurement error. We studied the reliability, magnitude and meaning of IQ change using scores on the WISC--R obtained from a representative sample of 794 children at ages 7, 9, 11 and 13. The findings suggest that, in the majority of children, IQ change is either negligible in amount, unreliably measured or both. In a nontrivial minority of children, naturalistic IQ change is marked and real, but this change is variable in its timing, idiosyncratic in its source and transient in its course. We discuss the implications of these findings for interventions that aspire to improve IQ scores. PMID- 8509491 TI - Parent and child views of parent-child relationship qualities and resilient outcomes among urban children. AB - Separate in-depth interviews were conducted with two groups of highly stressed 4th-6th grade urban children classified as stress-affected (SA) and stress resilient (SR), and their parents. Judges identified interview items reflecting three components of a good parent-child relationship, i.e. positive parental attitudes, involvement and guidance. SR parents and children scored higher than their SA counterparts on all three relational dimensions. Additionally, SR parent child dyads had more congruent views of their relationship than SA dyads. These findings suggest that positive parent-child relationship qualities play an important protective role that favors resilient outcomes, at ages 10-12, among children who have experienced major life stress. PMID- 8509492 TI - The evaluation and treatment of sleep disturbances in young children. AB - This study examines the accuracy of parents' reports about their children's sleep behavior and their response to a behavioral treatment. Twenty-eight sleep disordered and thirty control children aged 12-36 months were filmed during three nights using an infrared camera and their sleep behavior compared with parental reports. There were significant differences among the groups with parents of good sleepers being less accurate in reporting on their children's sleep behavior. Poor sleepers also had more behavior problems, a more difficult temperament and more adverse early medical histories. The good sleepers woke up as frequently as the poor sleepers. However, they managed to soothe themselves back to sleep without disturbing anyone. Virtually all poor sleepers showed significant improvement following treatment. PMID- 8509493 TI - Predicting substance use in early adolescence based on parent and teacher assessments of childhood psychiatric disorder: results from the Ontario Child Health Study follow-up. AB - This article examines relationships between psychiatric disorder, poor school performance, family dysfunction and low family income in a cohort of 8-12-year olds and use of tobacco, marijuana and hard drugs 4 years later. Conduct disorder assessed by teachers predicted use of alcohol and hard drugs, while low family income and poor school performance predicted use of tobacco. Neither attention deficit disorder nor emotional disorder was related to adolescent substance use. Although behavioural deviance in childhood is associated with adolescent substance use, it has limited potential for identifying groups at risk in the general population for purposes of preventing substance use in later years. PMID- 8509494 TI - Adopted and biological children in the clinic: family, parental and child characteristics. AB - Adopted children are overrepresented in referrals to mental health facilities. Research has described child symptomatology but has rarely described family characteristics or how adoptive and biological families presenting a child for treatment differ. This study took a systemic approach carrying out a multilevel assessment of families of adopted and biological children presented for treatment with adopted and biological nonclinical comparison groups. The results from this study of 88 parents of 7-17-year-old children suggest that adoptive families have greater social and psychological resources that can be relied on in treatment. However, adopted children are perceived to have more problems and their families are more likely to consider removal of the child as a solution to problems. Therapists' failure to appreciate these unique strengths and vulnerabilities of adoptive families can lead to treatment failure. PMID- 8509495 TI - The stability of fears in children: a two-year prospective study: a research note. AB - This study investigated the stability of self-reported fears amongst 94 primary school children over a 2-year period using the Fear Survey Schedule for Children- Revised (FSSC--R). Children reported a decrease in fearfulness with increasing age, with girls reporting higher fear scores than boys on both occasions. The most frequently feared stimuli were almost identical for boys and girls and remained the same on both occasions, relating mainly to fears of danger, death and physical injury. Those fears that showed the greatest reduction over time concerned getting sick, parental criticism or punishment and the dark for girls, whereas boys reported the greatest reductions in fears relating to physical injury, parental criticism, the dark and unfamiliar persons. The only fear stimulus to increase with age was "giving a spoken report", which was rated as more fearful by boys on the second occasion. Children identified as unusually fearful at Time 1, were much more likely to report high fear levels two years later, compared to children who did not report high fear levels at Time 1. PMID- 8509496 TI - Debate and argument: interpretation of auditory impairment and markers for brain damage in autism. PMID- 8509497 TI - D2-like dopamine receptors in amphibian retina: localization with fluorescent ligands. AB - Dopamine induces several light adaptive changes in amphibian retina via receptors with D2-like pharmacology, but the identity of the primary target cells has not been determined. Using a fluorescent probe consisting of a selective D2 antagonist, N-(p-aminophenethyl)-spiperone (NAPS), derivatized with the fluorophore Bodipy (NAPS-Bodipy), we identified the distribution of dopamine binding sites in the retina of two amphibians, post-metamorphic Xenopus laevis and larval Ambystoma tigrinum. Specific labeling was defined as staining that was displaced by D2 selective ligands (eticlopride or sulpiride), but insensitive to D1 selective drugs (SCH 23390), adrenergic catecholamines (epinephrine or norepinephrine), or serotoninergic analogues (ketanserin). Both rod and cone cells showed specific dopamine D2-like binding sites arranged in clustered arrays on discrete membrane domains of the inner segment. Labeling of photoreceptor outer segments was continuous and was not displaced by competition with D2 selective ligands; this labeling was considered nonspecific. In addition, in both species, clustered binding of the D2-probe was found on Muller cells and on a subset of inner retinal cells with the morphology of amacrine/interplexiform cells. Our data provide direct evidence for D2 receptors on both rods and cones, and suggest that the receptors may be clustered into patches within a discrete cellular domain, the inner segment. PMID- 8509498 TI - Intracellular injection of neurobiotin or horseradish peroxidase reveals separate types of preganglionic neurons in the sacral parasympathetic nucleus of the cat. AB - Sacral preganglionic neurons are essential to the neural control of the excretory and sex organs. Previously employed multi-cell tracing methods have certain limitations in the precise morphological analysis of the neural pathways that control these organs. These limitations were overcome by the intracellular injection of neurobiotin or horseradish peroxidase into single preganglionic neurons in the lateral sacral parasympathetic nucleus of the cat. Following light microscopic examination, these neurons, as a group, were found to have an average of five stem dendrites, which divided into 15 dendritic end-branches that were distributed among eight dendritic terminal fields. These dendrites had a major transverse orientation and were quite long, many of them reaching well into the dorsal and ventral horns and into the dorsal gray commissure. These dendrites also exhibited a major longitudinal orientation, extending an average of 869 microns (combined length of rostral and caudal dendrites) within the nucleus. Two groups of cells emerged on the basis of different dendritic patterns. Cells classed as Type I had dendrites in lamina I and in the ventral horn but lacked a significant projection into the lateral funiculus. Cells classed as Type II had major dendritic projections into the lateral funiculus but lacked dendrites in lamina I. The diverse dendritic patterns of these two cell types indicate dissimilar afferent control mechanisms and suggest that these preganglionic neurons may innervate different target organs. PMID- 8509499 TI - Pigment-dispersing hormone-like peptide in the nervous system of the flies Phormia and Drosophila: immunocytochemistry and partial characterization. AB - beta-pigment-dispersing hormone (beta-PDH) isolated from the fiddler crab (Rao et al., '85) is a member of an octadecapeptide family of neuropeptides common to arthropods. Whereas earlier studies of these peptides in insects were limited to orthopterans, this investigation focuses on dipteran flies. Extracts of heads from the blowfly Phormia terraenovae were assessed in a fiddler crab bioassay for PDH activity. Immunocytochemistry, dose-response curves, gel filtration chromatography and reversed-phase HPLC, combined with bioassay and enzyme-linked immunosorbent assay (ELISA), indicate the presence of PDH-like peptide in the blowfly. Immunocytochemical mapping of PDH-like immunoreactive (PDHLI) neurons was performed for the entire nervous systems of Phormia and the fruitfly Drosophila with a beta-PDH antiserum. In the cephalic ganglion (brain, optic lobe and subesophageal ganglion) PDHLI cell bodies could be detected (34 in Phormia and 16 in Drosophila). In both species, each hemisphere contains 8 PDHLI cell bodies in the optic lobes. These innervate the optic lobe neuropils bilaterally. In Phormia, another set of 8 cell bodies are located in each of the lateral neurosecretory cell groups in the superior protocerebrum. These neurons send axons to the corpora cardiaca-hypocerebral ganglion complex and to portions of the foregut. In contrast, only the optic lobe neurons display immunoreactivity in Drosophila. Except for the optic lobes, PDHLI processes are distributed only in nonglomerular neurophils of the brain of both species. In the fused thoracico abdominal ganglia of Phormia, 28 PDHLI cell bodies were found (only six were found in Drosophila). In both species, six abdominal PDHLI neurons are efferents with axons innervating the hindgut. We also found that some of the PDHLI neurons in the Phormia brain and abdominal ganglion contain colocalized FMRFamide-like immunoreactivity. Since the flies studied here do not display hormonally controlled, fast pigment migrations, the PDH-like peptide may have a role as neurotransmitter or neuromodulator in the central nervous system, especially in the visual system, and a regulatory role in the stomatogastric system and the hind-gut. PMID- 8509500 TI - Selective sparing of later-born ganglion cells after neonatal transection of the infraorbital nerve. AB - A combination of [3H]thymidine labelling and retrograde tracing with either horseradish peroxidase (HRP) or true blue (TB) was used to determine whether V primary afferent neurons born on different embryonic (E) days were differentially susceptible to neonatal transection of the infraorbital nerve (ION). In one experiment, rat fetuses were exposed to [3H]thymidine on E-8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, or 15.5, the left infraorbital nerve (ION) was transected on the day of birth, and both the regenerate and intact IONs were labelled with HRP when the animals reached adulthood. The percentage of HRP labelled cells that were also heavily labelled by [3H]thymidine was calculated for both the intact ganglion and that ipsilateral to the damaged nerve for each animal. A consistently higher percentage of double labelled cells on the lesioned rather than on the intact side for a given E-day was taken as an indication that cells born on the day in question had an increased probability of survival relative to the entire population of V ganglion cells that contributed axons to the ION. Cells born late in gestation on E-12.5 through 14.5 were significantly more likely than early born (E-9.5 through 11.5) cells to survive neonatal axotomy. In a second experiment, fetuses were exposed to [3H]thymidine on either E-9.5, E 10.5, or E-14.5, the vibrissa pads on both sides of the face were injected with TB within 6 hours of birth, and the ION was transected 6-8 hours later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509502 TI - Distribution of choline acetyltransferase immunoreactivity in the brain of the lizard Gallotia galloti. AB - The aim of the present study is to provide a complete description of the distribution of choline acetyltransferase (ChAT) immunoreactivity (i) in the brain of the lizard Gallotia galloti, on the basis of two different primary antisera: rat anti-ChAT and rabbit anti-chicken ChAT. Considering that the brain is a segmented structure, we have analysed our data with respect to transverse segmental domains (or neuromeres), which have been previously described by several authors in the brain of vertebrates. In the telencephalon, ChATi neurons are seen in the cortex, anterior dorsal ventricular ridge, basal ganglia, diagonal band, and bed nucleus of the stria terminalis. Further caudally, ChATi cell bodies are located in the preoptic area, hypothalamus, habenula, isthmus, and all motor efferent centers of the brainstem and spinal cord. Plexuses of ChATi fibers are observed in the areas containing cholinergic cell bodies. In addition, distinct plexuses are found in the cortex, the posterior dorsal ventricular ridge, the neuropiles of all primary visual centers of the diencephalon and mesencephalon, and several non-visual nuclei of the brainstem. The distribution of ChAT immunoreactivity in the brain of G. galloti resembles in many respects that of other vertebrates, and differences are mainly observed in the pretectum and midbrain tectum. Transverse segmental domains were identified in the brainstem and forebrain of Gallotia when the cranial nerve roots and fiber tracts were used as a reference, and most cranial motor nuclei were found to occupy the same segmental positions as have been reported in the chick. PMID- 8509501 TI - Projections of physiologically characterized spherical bushy cell axons from the cochlear nucleus of the cat: evidence for delay lines to the medial superior olive. AB - Bushy cells in the anteroventral cochlear nucleus (AVCN) receive their principal excitatory input from the auditory nerve and are the primary source of excitatory input to more centrally located brainstem auditory nuclei. Despite this pivotal position in the auditory pathway, details of the basic physiological information being carried by axons of these cells and their projections to more central auditory nuclei have not been fully explored. In an attempt to clarify these details, we have physiologically characterized and anatomically labeled individual axons of the spherical bushy cell (SBC) class of the cat AVCN. The characteristic frequencies (CFs) of our injected SBC population are low, all less than 12 kHz and primarily (83%) less than 3 kHz, while their spontaneous activity is comparatively high (mean of 59 spikes/sec). In response to short tone bursts at CF, low CF (< 1 kHz) SBC units can phase-lock better than auditory nerve fibers. SBCs with CFs above 1 kHz have primary-like responses at all stimulus levels and can show robust phase-locking to an off-CF, 500 Hz tone. When compared with our previously reported population of labeled globular bushy cells (GBC; Smith et al., 1991, J. Comp. Neurol. 304:387-407), some similarities and differences are apparent in both physiological response properties and axonal projection pattern. GBCs show no low frequency bias in CFs, have lower spontaneous rates, and the high CF units exhibit a primary-like-with-notch response at high stimulus levels as a consequence of a very well timed onset component. Low CF, GBC short tone responses are indistinguishable from those of SBCs. Anatomically, the axons of SBCs cross the midline in the dorsal component of the trapezoid body and typically innervate the medial superior olive (MSO) on both sides, the ipsilateral lateral superior olive (LSO), and the contralateral ventral nucleus of the lateral lemniscus (VNLL). The projections to the contralateral, but not the ipsilateral MSO, show a rostral to caudal delay line configuration, similar to the scheme first proposed by Jeffress (1948, J. Comp. Psychol. 41:35-39). The form of this delay line is consistent with the topographic map of interaural time delays reported by Yin and Chan (1990, J. Neurophysiol. 64:465-488). Projections to the ipsilateral LSO often take an indirect route. In contrast, GBC axons travel in the ventral component of the trapezoid body, never innervate the MSO, rarely innervate the ipsilateral LSO, and always innervate the contralateral medial nucleus of the trapezoid body. The terminal specializations of both SBC and GBC axons contain round vesicles. PMID- 8509503 TI - Compartmental origin of the striato-entopeduncular projection in the rat. AB - The mammalian neostriatum is divisible into neurochemically and cytoarchitectonically distinct striosome and matrix compartments. This compartmentalization is respected by many afferent and efferent projections of the striatum. The distribution of distinct types of neuroactive substances and receptors and the unique connections of the striosome and matrix suggest a functional segregation between these compartments. The present study examines the organization of efferent projections from each of the striatal compartments to the entopeduncular nucleus (EPN), a major output center of the basal ganglia. The fluorescent retrograde tracer fluorogold, or rhodamine-conjugated dextran, was injected into the lateral habenula or the ventrolateral nucleus of the thalamus of adult Wistar rats to identify the topographical organization of EPN-habenular and EPN-thalamic neurons. Fluorogold was then placed into the rostral or caudal parts of the EPN, identified from the previous experiment as areas containing predominantly EPN-habenular or EPN-thalamic neurons, respectively. Sections containing retrogradely labeled neurons in the neostriatum were simultaneously immunolabeled for calbindin-D28kDa, a calcium-binding protein found exclusively in the projection neurons of the matrix. The results indicate that the striatal projection to the EPN-habenular and EPN-thalamic parts of the EPN originates from striosome and matrix neurons, respectively. The duality of striatal outflow involving the EPN suggests a mechanism whereby the striosome is integrated into subcortical pathways that modulate the activity of the basal ganglia via the ascending serotoninergic projection from the dorsal raphe nucleus, whereas the matrix is involved in a loop that includes the thalamus and the cerebral cortex. PMID- 8509504 TI - Laterality of superior olive projections to the inferior colliculus in adult and developing ferret. AB - The laterality of projections from the lateral superior olivary nucleus (LSO) to the inferior colliculus was studied in adult and immature postnatal ferrets. In the adult ferret, large unilateral injections of horseradish peroxidase (HRP) in the inferior colliculus labeled about equal proportions of cells in the ipsilateral and contralateral lateral superior olivary nuclei. The contralateral labeled cells consistently were more densely labeled than those on the ipsilateral side. Double labeling experiments using fluorescent dyes indicated that only about 3% of LSO cells in the adult give rise to collaterals ending in the inferior colliculus on both sides. As expected, the distribution of labeled cells varied topographically in the LSO as a function of the injection site in the inferior colliculus. Dorsolateral inferior collicular injections labeled cells in the lateral limb of the LSO, whereas ventromedial injections labeled cells in the medial limb of the LSO. The proportion of ipsilateral and contralateral labeled cells also varied across the lateral-medial axis of the LSO in some cases. A gradient in laterality was observed in these cases with the lateral limb of the LSO containing the highest proportion of contralateral labeled cells, and the medial limb, the highest proportion of ipsilateral labeled cells. Larger inferior collicular injections resulted in greater proportions of ipsilateral labeling in LSO than smaller injections. Finally, ipsilateral labeled cells tended to be in the marginal region of the LSO, whereas contralateral labeled cells were more common within the core region of the LSO, irrespective of the location along the lateral-medial axis of LSO. The contralateral predominance of labeled cells, greater density of labeling in contralateral cells, different topographic distribution, and regional segregation of ipsilateral and contralateral labeled cells were typical of the LSO in ferret kits by birth, one month before the onset of hearing. Nevertheless, the relative proportion of ipsilateral and contralateral projection cells appears to change during postnatal development. PMID- 8509505 TI - Localization of D2 dopamine receptors in vertebrate retinae with anti-peptide antibodies. AB - Dopamine plays an important role in modulating various aspects of retinal signal processing. The morphology of dopaminergic neurons and its physiological effects are well characterized. Two classes of receptor molecules (D1 and D2) were shown pharmacologically to mediate specific actions, with differences between individual groups of vertebrates. In an attempt to better understand dopaminergic mechanisms at the cellular level, we used antisera against D2 receptors and investigated the localization of the dopamine D2 receptor in the retinae of rat, rabbit, cow, chick, turtle, frog, and two fish species with immunofluorescence techniques. Antisera were raised in rabbits to two oligopeptides predicted from rat D2 receptor cDNA; one specific for the splice-variant insertion in the third cytoplasmic loop and the other directed towards the extracellular amino terminal region shared by both short and long isoforms. Preadsorption with the synthetic peptide resulted in a significant reduction of label, indicating the presence of specific binding in all species except turtle and goldfish. The pattern of labelling produced by the two antisera was essentially identical; however, the staining obtained with antiserum to the extracellular motif was always more intense. Specific staining was present in photoreceptor inner and outer segments, and in the outer and inner plexiform layers of all species. In mammals and chick, strongly fluorescent perikarya were observed in the ganglion cell layer and at the proximal margin of the inner nuclear layer. Label may be present in the pigment epithelium but could not be established beyond doubt. This pattern of labelling is in accordance with previous observations on D2 receptor localization by means of radioactive ligand binding and in situ hybridization techniques. It suggests that retinal dopamine acts as a neuromodulator as well as a transmitter. In the distal retina, it may reach its targets via diffusion over considerable distances, even crossing the outer limiting membrane; in the inner and outer plexiform layers, conventional synaptic transmission seems to coexist with paracrine addressing of more distant targets, and D2 receptors are expressed by both amacrine and ganglion cells. PMID- 8509506 TI - Ipsilaterally projecting retinal ganglion cells in Xenopus laevis: an HRP study. AB - The routes of ipsilaterally projecting retinal ganglion cell axons in the visual pathway of young postmetamorphic Xenopus laevis were studied by anterograde and retrograde transport of horseradish peroxidase (HRP). In the retina, most cells heavily labeled from injections in ipsilateral thalamus are large multipolar ganglion cells. They are found exclusively in the posterior half of the retina, and their axons occupy a central position in the optic nerve head. Immediately behind the eye, axons of ipsilaterally projecting axons leave the core of the nerve and regroup around the circumference of the nerve. The nerve increases in diameter in the region where the fibers reorganize, and pigmented processes are seen in this region of the nerve. At the point where the optic nerve enters the brain case through the optic foramen, the fibers undergo a second reorganization which results in a laminar arrangement of ipsilaterally projecting axons at the ventral margin of the intracranial portion of the nerve. As soon as the nerve touches the brain, uncrossed axons begin to turn toward the ipsilateral side rather than proceeding further towards the midline of the chiasm. These uncrossed axons keep their internal topographical order at least at the beginning of the marginal tract. All ipsilaterally projecting axons run at the rostral edge of the marginal tract at the lateral wall of the brain until they reach their terminal fields in the thalamic visual nuclei. PMID- 8509507 TI - Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat. AB - The distribution of fos-like-immunoreactivity (fos-LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, in order to evaluate the use of fos as a marker for neuronal activation in trigeminal nociceptive pathways. Control animals that received urethane anesthesia and no facial stimulation showed substantial bilateral labeling in the trigeminal complex that was restricted to one rostrocaudal level, at the transition between the medullary dorsal horn (nucleus caudalis) and nucleus interpolaris. Noxious mechanical stimulation (pinch) of different facial sites produced labeling in the ipsilateral dorsal horn whose distribution varied predictably with the rostrocaudal and dorsoventral position of the facial stimulation site, such that rostral facial sites were represented rostrally in the dorsal horn and dorsal sites were represented ventrolaterally. The cornea was exceptional among the facial stimulation sites in that it had a specific representation at two distinct rostrocaudal levels, in C1 and the interpolaris-caudalis transition region; the position of the rostral peak was somatotopically inappropriate, based on the representation of other facial sites. The proportion of labelling in laminae III IV relative to laminae I-II was higher with noxious mechanical stimulation than with noxious thermal (55 degrees C) or chemical (subcutaneous injection of capsaicin) stimulation. The proportion of labelling in laminae III-IV produced by electrical stimulation of the infraorbital nerve was no greater than that produced by pinch. The results suggest that fos-LI mapping can be a useful method for the investigation of somatotopy but is subject to serious limitations when used for the investigation of laminar organization. The results also suggest that the interpolaris-caudalis transition region may have properties that are distinct from those of the rest of the trigeminal complex, possibly related to an involvement in autonomic function. PMID- 8509508 TI - Propriospinal input to thoracolumbar sympathetic nuclei from cervical and lumbar lamina I neurons in the cat and the monkey. AB - The possibility that specific thermoreceptive and nociceptive influences on sympathetic outflow are conveyed directly to spinal sympathetic regions by lamina I neurons was investigated anatomically with the immunofluorescent PHA-L technique in the cat and the cynomolgus monkey. Iontophoretic injections made with physiological guidance were restricted to lamina I or to laminae I-II in the cervical (C6-8) or lumbar (L6-7) enlargement. Bilateral (symmetric) terminal arborizations were observed (with an ipsilateral predominance) in the intermediolateral, intermediomedial, and intervening regions of the thoracolumbar intermediate zone. In serial horizontal sections, patches of terminal labeling appeared at regular longitudinal intervals in the intermediolateral region. Longitudinally coursing fibers that had multiple varicosities and gave off small terminal branches were observed in the intermediolateral and the intermediomedial regions. Mediolateral strips of labeling that extended from labeling in the intermediolateral region to labeling in the intermediomedial region occurred at fairly regular longitudinal intervals. Because the longitudinal distribution of these terminations corresponds very well with the characteristic (ladder-like) longitudinal pattern of organization of the neuropil of the thoracolumbar sympathetic nuclei, i.e., the principal part of the intermediolateral cell column, the central autonomic n., and the intervening n. intercalatus, it is inferred that these lamina I terminations occur within these nuclei. After cervical injections, the labeling was most dense in the upper thoracic T2-4 spinal cord segments in both the cat and the monkey; labeling was also present in the T10-12 segments. After lumbar injections, labeling in the cat was located in the L4 segment; labeling in the monkey was present in the T4-6 and T10-12 segments. The labeling obtained was much more dense in the monkey than in the cat. These observations reveal a spinal lamina I projection that could provide a direct pathway for the somatosympathetic reflex effects of thermal and noxious stimuli. Considered together with reports that lamina I and the sympathetic nuclei both receive descending input from certain key autonomic regions, this result emphasizes the importance of lamina I for homeostasis, in addition to its probable roles in behavioral arousal, affect, and sensation. These observations thus support the proposed concept that lamina I processes and distributes in a functionally specific manner the sensory input relevant to the physiological status of the tissues and organs of the entire organism. PMID- 8509509 TI - Immunohistochemical studies on neurofilamentous hypertrophy in degenerating retinal terminals of the olivary pretectal nucleus in the rat. AB - Following section of the optic nerve, degenerating retinal terminals reveal an accumulation of neurofilaments (neurofilamentous hypertrophy) as demonstrated by silver impregnation techniques or electron microscopy. The present study examined degenerating retinal terminals by means of immunohistochemistry and antibodies specific for the triplet of neurofilament proteins of low (NF-L), medium (NF-M), and high (NF-H) molecular weight class. Following unilateral optic nerve section in the rat and survival of 1, 2, 4, 8, and 21 days, brains were perfused with aldehyde fixative, sliced on a vibratome and stained for neurofilaments by using the peroxidase-antiperoxidase technique. Other brains were frozen, cut in the native state, and slide-mounted sections were fixed by acetone. Side comparisons in visual pathways were made in frontal sections, taking advantage of the near complete crossing of retinal fibers in the rat. Anterograde degeneration of axons occurred in the optic tract and branchium colliculi. Changes of terminals were investigated in the olivary pretectal nucleus, which contains a dense aggregation of retinal terminals in the core region. The optic tract and branchium colliculi showed a reduction in immunostaining for neurofilament proteins following axotomy. Within the core region of the olivary pretectal nucleus, strong increases of immunoreactivity of NF-L and NF-M were detected beginning at 2 days postlesion and persisting at 8 days. No changes in NF-H proteins were found in the terminal regions with three different antibody probes. The increase in immunostaining reflects the accumulation of neurofilament proteins in the degenerating retinal terminals, i.e., neurofilamentous hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509510 TI - Purkinje cell dendrites in staggerer<-->wild type mouse chimeras lack the aberrant morphologies found in lurcher<-->wild type chimeras. AB - In lurcher<-->wild type mouse chimeras (lurcher chimeras), mutant Purkinje cells are transiently present and probably provide target support for afferent granule cells during the sensitive period of target-dependent cell death. Previous studies demonstrate that wild type Purkinje cells in the cerebella of mature lurcher chimeras often have atrophic dendritic morphologies, leading to the hypothesis that developmental deafferentation of wild type Purkinje cells occurs uniquely in lurcher chimeras following the period of mutant Purkinje cell loss. Other studies document the survival of a disproportionately large number of granule cells in these animals. Based on cell birthdate analyses, the hypothesis further proposes that deafferentation induces an up-regulation of trophic activity among the Purkinje cell population and the consequent rescue of late generated granule cells that might otherwise be lost to target related cell death. In the present study, we take advantage of phenotypic differences between the staggerer and lurcher mutations to test this hypothesis. While staggerer<- >wild type chimeras (staggerer chimeras) resemble lurcher chimeras in several respects, including extensive cell loss, they differ in that staggerer Purkinje cells never provide target support for granule cells. Hence the hypothesis predicts that Purkinje cells in these animals should not exhibit the atrophic morphologies found in lurcher chimeras. We have developed a new semiquantitative method for scoring dendritic morphology in a large number of Golgi-impregnated cells. We have used this method to characterize the distribution of wild type Purkinje cell morphologies in staggerer chimeras, and to compare these with the corresponding distributions of morphologies in lurcher chimeras and wild type<- >wild type chimeras. We find that morphologies in staggerer chimeras closely resemble those in control chimeras. Furthermore, Purkinje cells in both staggerer and wild type chimeras differ significantly from those in lurcher chimeras. These results confirm a direct prediction of the hypothesis. PMID- 8509511 TI - Morphological and quantitative evaluation of olfactory bulb development in Xenopus after olfactory placode transplantation. AB - We found previously that the number of olfactory axons is correlated with the number of mitral/tufted cells (output neurons of the olfactory bulb) during normal larval development. To examine the significance of this quantitative relationship, we evaluated the effects of transplanting an extra olfactory placode on the development of the larval olfactory bulb. We found that the transplanted tissue retained the normal, pseudostratified, columnar appearance and had the same cell types as normal olfactory epithelium, and the olfactory bulbs had the same laminar organization as control bulbs. With gross examination of the olfactory bulb, the side innervated by the transplant appeared slightly larger than the contralateral side in animals analyzed at a young larval stage (stage 50) and in 2 of the 9 animals examined at late larval stages (57/58). Tissue sections and area measurements, however, revealed that the volume of the olfactory bulbs in animals with a transplant was not significantly different from control values. Our quantitative analysis also showed that in stage-50 animals with a transplant, the total number of olfactory axons (in nerves from the transplanted and host olfactory organs) appeared to be greater than in control animals, but not to a statistically significant level. The number of mitral/tufted cells was not different from controls. In animals examined at stage 57/58, there was no difference from controls in either the total number of olfactory axons, total number of mitral/tufted cells, or convergence ratio of olfactory axons onto mitral/tufted cells. Thus, in the late-stage larvae, the quantitative relationship between olfactory axons and mitral/tufted cells was not altered by the experimental manipulation. These results suggest that the olfactory bulb can regulate the number of afferent fibers. PMID- 8509512 TI - Spatial and temporal differences between the expression of short- and middle-wave sensitive cone pigments in the mouse retina: a developmental study. AB - In an earlier study we found a topographic separation of middlewave-sensitive (M) and shortwave-sensitive (S) cones in the adult mouse retina. In the present study we investigated the development of the two colour-specific cone types to see whether there is also a temporal difference between the expression of the specific cone visual pigments. Using two anti-cone visual pigment antibodies, COS 1 and OS-2, we compared the densities of immunopositive cone outer segments on retinal whole mounts derived from mice of various ages. The first detectable cone outer segments were the S-cones which appeared in the inferior half of the retina on postnatal day 4. At this stage, the density of the S-cones was very low (30-40 cones/retina) but increased steadily on the following days to reach a value comparable to that of adults by P30 (18,000/mm2). This cone type always remained much more abundant in the lower part of the retina throughout the whole retinal development. In the superior half of the retina, a few S-cones appeared from postnatal day 7; however, their number always remained about one order of magnitude lower than in the inferior part. In contrast, M-cone outer segments were not identifiable earlier than postnatal day 11 and were confined exclusively to the superior part of the retina during the whole developmental process. On postnatal day 12, their density was 1,900/mm2 and increased to a value of 11,000/mm2 by postnatal day 30, which represented the adult stage. As shown by comparison of isodensity lines derived from immunocytochemical reactions of whole mount retinas, the two cone types occupied complementary halves of the mouse retina with maximum density centres located in opposite retinal quadrants. We conclude that 1) in contrast to the primate retina, mouse S-cones precede the M cones in their development, and 2) the spatial arrangements of the two cone types is maintained throughout the whole differentiation process. PMID- 8509513 TI - Histologic preparation for Mohs micrographic surgery. The single section method. AB - BACKGROUND: Tissue processed by Mohs micrographic surgery is usually cut into several sections before it is processed. OBJECT AND METHODS: We describe a single section method, in which the tissue is not subdivided, for preparing a tissue specimen for histologic examination in Mohs micrographic surgery. RESULTS: This technique saves time for both technicians, who prepare fewer specimens, and physicians, who have fewer histologic specimens to interpret. It may minimize false-positive margins and technical errors. CONCLUSIONS: Small specimens are handled best by this technique; however, the size of the specimen is limited only by the size of the cryostat chuck and histologic slide. The single section method is technically more difficult for preparing specimens that contain cartilage or ones that are extremely concave or convex, such as specimens from the conch of the ear. PMID- 8509514 TI - Use of cryotherapy in the treatment of keloids. AB - BACKGROUND: Numerous approaches are used to treat keloids, but none is ideal for all scars and recurrence after treatment is frequent. OBJECTIVE: The purpose of this study was to evaluate the efficacy of cryotherapy for treatment of these scars. METHODS: Sixty-five lesions of various sizes and ages were treated with a hand-held liquid nitrogen spray unit; freeze times and number of sessions varied. Scar volume was measured before and after treatment. RESULTS: Complete flattening was achieved in 48 scars (73%), most of which were less than 2 years old. Unacceptable responses were seen in six scars. No recurrence was seen during follow-ups ranging from 17 to 42 months. Side effects were limited to hypopigmentation and slight to moderate atrophy in three cases. CONCLUSION: Cryotherapy is an effective, low-risk approach to keloid treatment associated with a low rate of recurrence. PMID- 8509515 TI - Intradermal augmentation with expanded polytetrafluoroethylene (Gore-Tex) for facial lines and wrinkles. AB - BACKGROUND: Many materials--from bovine and porcine collagen to autologous fat- have been used to augment tissue for wrinkle correction or to correct cosmetic defects. However, none of them has proved completely satisfactory because of host immune response or lack of staying power. OBJECTIVE: To describe the use of expanded tetrafluoroethylene (Gore Tex E-PTFE Soft Tissue Patch) in the correction of deep nasolabial folds, facial wrinkles, and lip contour irregularities. METHODS: The physicochemical and biological characteristics of Gore-Tex E-PTFE (inert material with highly porous structure) allow the penetration of cells and vessels with minimal inflammatory reaction. Small pieces of Gore-Tex patches or threads were inserted underneath the wrinkle to fill it out. To avoid the appearance of the thread's end through the needle puncture in the skin, the accordion technique of insertion was used. RESULTS: Expanded polytetrafluoroethylene has been used as a subdermal implant for the correction of deep nasolabial folds, facial wrinkles, and lip contour irregularities in 53 cases with satisfactory results. CONCLUSIONS: It is concluded that Gore-Tex E PTFE is a new thread augmentation advance in the solution of facial skin irregularities that yields satisfactory and permanent results. PMID- 8509516 TI - Suppression of the delayed type hypersensitivity response by tumor facilitating factor of B16 melanoma. A tumor factor suppresses immune responses. AB - BACKGROUND: Tumor facilitating factor is a cell surface glycoprotein produced by B16 melanoma that has been found to reduce the lethal inoculum for B16. Tumor facilitating factor induces macrophage spreading in vitro, reduces macrophage chemotaxis in vivo, and depresses lymphocyte mitogenesis in vitro. OBJECTIVE: It is assumed that the immune modifying effects are responsible for tumor facilitation. As tumors may be poor immunogens or inducers of inflammation, studies were conducted to determine whether tumor facilitating factor alters the inflammatory cascade of cells found in infiltrates of delayed type hypersensitivity. RESULTS: Freeze-thawed B16 cells, used as the source of TFF, caused a suppression of delayed type hypersensitivity measured as ear swelling in the mouse. When culture supernatant was substituted for freeze-thawed cells as a source of TFF and injected at different time points of the delayed type hypersensitivity response, the greater suppression was with tumor facilitating factor injections at 24 hours pre-elicitation only (82%), and 24 hours both presensitization and pre-elicitation (89%). Immunohistological staining demonstrated that tumor facilitating factor decreases ear thickness and cellular infiltrates, specifically Mac-1 staining cells, to a site of delayed hypersensitivity. Peritoneal cell analysis confirmed these findings. CONCLUSION: These data are consistent with the hypothesis that tumor facilitating factor alters immune functions including macrophage and lymphocyte mobility and recruitment to a target site, thereby allowing for facilitation of tumor growth. PMID- 8509517 TI - The nasolabial fold donor site for full-thickness skin grafts of nasal tip defects. AB - BACKGROUND: The nasal tip has unique skin texture, geographic, and topographic qualities that frequently make repair of defects in this area difficult from the standpoint of function and cosmesis. OBJECTIVE: To assess seven outcome variables of function and cosmesis in 41 patients who underwent nasolabial graft repair for nasal tip defects. METHODS: A retrospective review of photographic and written records as well as person to person and phone interviews with 41 patients who underwent nasolabial graft repair of nasal tip defects after Mohs micrographic surgery was performed. Seven outcome variables were assessed. Follow-up periods ranged from 3 to 28 months. RESULTS: Patient and doctor evaluators rated overall outcome as good or excellent in 95% and 89% of cases respectively. CONCLUSION: We consider the nasolabial graft to be an important reconstructive option for nasal tip defects when the underlying cartilage is not involved. PMID- 8509518 TI - Collagen gene expression and wound strength in normal and radiation-impaired wounds. A model of radiation-impaired wound healing. AB - BACKGROUND: Poorly healing wounds result in significant morbidity postoperatively. Numerous attempts have been made to study wound healing in vivo to understand better the normal healing process and factors that impair healing. Animal models of wound healing have been developed to evaluate wound healing in a systematic and controlled setting. Incisional wounds are created in animals to mimic the surgical patient. They may then be evaluated by a variety of methods for degree of healing. OBJECTIVE: To give insight into the mechanisms of wound healing impairment, we developed a model of impaired wound healing in guinea pigs using radiation applied to the skin surfaces only. METHODS: Wound bursting strength, a direct measure of the force required to burst apart healing linear incisions, was measured. Collagen content, measured indirectly as collagen gene expression, was measured. RESULTS: Significant reductions in wound bursting strength were noted after radiation administration. Collagen gene expression was decreased in wounds 7 days after radiation, but recovered to control levels 14 days after irradiation. Our model enables the inclusion of irradiated and unirradiated skin flaps within the same animal, thus eliminating intra-animal variation when comparing impaired and normal wounds. CONCLUSION: Wound bursting strength analysis, combined with techniques aimed at elucidating changes at the molecular level, provides a useful tool for the study of factors that impair healing and potential treatments for resulting healing deficits. PMID- 8509519 TI - Medical and technical issues in office electrolysis and thermolysis. AB - BACKGROUND: Most university medical centers do not directly offer electrolysis or thermolysis services to hirsute patients. Little research activity has been focused on these procedures. The successful introduction of a clinical and research electrolysis service into the University of Texas Medical Branch (UTMB) dermatology clinic is described. OBJECTIVE: The purpose of this communication is to familiarize clinicians with an electrolysis service in a university clinic setting. New advances in permanent hair removal equipment and methods are reviewed. METHODS: A description of the UTMB electrolysis clinic is given. RESULTS: Electrolysis services offered by the UTMB dermatology department have been well received by patients, clinical staff, UTMB faculty, UTMB resident physicians, and private physicians. CONCLUSION: This successful medical model for electrolysis services may provide other university dermatology clinics with background information for the development of their own programs. Future research advances in electrolysis and the management of hirsutism may result from this activity. PMID- 8509520 TI - Management of patients taking anticoagulants and platelet inhibitors prior to dermatologic surgery. AB - BACKGROUND: The use of anticoagulants and platelet inhibitors can increase the risk of intraoperative and postoperative hemorrhagic complications in cutaneous surgery. Currently there are no general guidelines and no consensus among dermatologic surgeons on how to manage patients taking these medicines. OBJECTIVE: To address many of the issues involved in the management of these patients. CONCLUSION: General recommendations are made for managing patients taking anticoagulants and platelet inhibitors prior to dermatologic surgery. PMID- 8509521 TI - Pseudocyst of the ear. Surgical treatment. AB - BACKGROUND: Pseudocyst of the auricle is characterized by an asymptomatic swelling caused by an intra-cartilaginous accumulation of fluid. Treatments include aspiration, steroid injection, and surgical intervention. OBJECTIVE: To present two cases of pseudocyst of the auricle treated surgically with an open, deroofing technique. METHODS: Two cases are presented and the relevant literature is reviewed. CONCLUSION: Optimal treatment for pseudocyst of the ear involves removal of the anterior cartilaginous leaflet of the pseudocyst with repositioning of the overlying flap of skin. This results in a normal-appearing auricle with minimal scarring or recurrence of the pseudocyst. PMID- 8509522 TI - Exclusion of close linkage of bipolar disorder to the dopamine D3 receptor gene in nine Australian pedigrees. AB - The recently cloned dopamine D3 receptor (DRD3) gene is of potential relevance to the aetiology of bipolar disorder because of an almost exclusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine whether bipolar disorder in nine pedigrees (with 171 members) was linked to this receptor gene, which has been mapped to chromosomal region 3q 13.3. Linkage of bipolar disorder and recurrent depression to the DRD3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness (ranging from bipolar I alone to all affective disorders). Close linkage to the DRD3 gene was strongly excluded using each model and definition, and these conclusions persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis. PMID- 8509523 TI - Plasma amino acid profiles in relation to clinical response to moclobemide in patients with major depression. Danish University Antidepressant Group. AB - With the aim of identifying predictors of treatment response, plasma levels of tryptophan (Trp) and tyrosine (Tyr) pretreatment and during treatment, and their ratios in plasma to the sum of the other large neutral amino acids (LNAA), were determined in 26 inpatients with major depression. The subjects were treated double-blind on a fixed-dose schedule for 4 weeks with the monoamine oxidase (MAO) inhibitor moclobemide. The study took place at 4 clinical centers. Endogenous and nonendogenous depressives were comparable in all biochemical variables and were therefore analysed together. The levels of plasma Trp/LNAA were decreased pretreatment and during treatment in the depressives compared with healthy controls. No significant correlation between plasma amino acid levels or ratios, or plasma moclobemide level, and clinical improvement was found, and there were no indications of a specific plasma amino acid profile associating with a favourable clinical response. Endogenous depressives showed significantly greater improvement than nonendogenous depressives; however, neither subgroup showed significant correlations between biochemical and clinical variables. The findings are at variance with a series of studies, which showed significant correlations between plasma amino acid ratios and clinical improvement on a variety of antidepressant treatments. PMID- 8509524 TI - Depression following traumatic brain injury: a 1 year longitudinal study. AB - A group of 66 patients hospitalized for the treatment of closed head injury, were assessed for the presence of mood disorders during their hospital admission and at 3, 6 and 12 months follow-up. A total 28 patients met DSM-III-R diagnostic criteria for major depression at some time during the study (17 in the acute stage, 11 during follow-up). The mean duration of major depression was 4.7 months. However, there appeared to be a group of transiently depressed patients (41%) who where depressed inhospital but were no longer depressed at 3 months follow-up. Throughout the follow-up period, major depression showed a strong relationship with poor social functioning. There was not, however, a consistent relationship between depression and quantitative measures of either physical or cognitive impairment. Location of the brain lesion was associated with the development of major depression only in the acute stage. Transient depressive syndromes were associated with left dorsolateral frontal and/or left basal ganglia lesions. PMID- 8509525 TI - Depressive symptoms and measures of disability: a prospective study. AB - OBJECTIVE: The purpose of this study was to test the hypothesis that decreases in severity of depressive symptoms in patients with chronic tinnitus would correlate with reductions in measures of functional disability. METHOD: This study describes the correlations between several measures of functional disability and Hamilton depression scores in two groups of patients with major depression and depressive symptoms (D-NOS) who were patients enrolled in a 12-week placebo controlled, double-blind trial of nortriptyline. These patients had chronic severe tinnitus which was associated in most patients with high frequency hearing loss. The effect of whether affective symptoms improved and the patient's initial depression status (major depression versus depressive symptoms) are examined in order to increase understanding about the correlations between depressive symptoms and functional disability. RESULTS: Most measures of functional disability decreased synchronously with Hamilton Depression Scale scores in both patients with major depression and those with subclinical depressive symptoms. Patients whose depression improved had a significantly greater change in each disability measure than patients whose depression did not improve. This significant decrease in functional disability was seen in 11 of 13 scales in the improved D-NOS group, versus only 3 of the 13 scales in the unimproved D-NOS group; 9 of 13 scales of functional disability significantly decreased in the improved major depression group, versus 3 of 13 scales in the unimproved major depression group. CONCLUSIONS: The results suggest that there was a significant correlation between improvement in both major depression and depression-NOS symptoms, and decreases in measures of functional disability in an aging population with a chronic medical illness. PMID- 8509526 TI - Psychomotor disturbance in depression: defining the constructs. AB - Four hundred and thirteen depressed patients were rated on eighteen signs of psychomotor disturbance, and the data examined by factor analyses. A three-factor solution was favoured. In addition to 'retardation' and 'agitation' dimensions (whose derived factor scores suggested independence of those two dimensions), a third 'non-interactive' dimension was evident--with derived factor scores correlating significantly with both the retardation and agitation dimensions. Thus, a 'trunk and branch' analogy was suggested for construing psychomotor disturbance, with a truncal 'psychic' component arborising into retardation and agitation 'motoric' expressions. Higher scores on all three factors were significantly linked with features weighted more to the melancholic 'type' of depression. PMID- 8509527 TI - Twice versus thrice weekly ECT in melancholia: a double-blind prospective comparison. AB - Thirty patients with major depressive disorder of melancholic subtype were randomly allocated to receive ECT either twice or thrice a week. Double-blind ratings on the Hamilton Scale for Depression and Clinical Global impression showed no differences in the outcome through 4 weeks of trial as well as at 6 month follow-up. Cumulative seizure duration was higher in the thrice weekly group but not significantly so in spite of having received a significantly greater number of ECTs. The results indicate that ECT given thrice a week conferred no advantage over ECT given twice a week. PMID- 8509528 TI - Cardiac Transplantation, 24th Bethesda Conference. November 5-6, 1992. PMID- 8509529 TI - Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia. AB - OBJECTIVES: This study assessed the efficacy of the combination of sotalol and either quinidine or procainamide in preventing sustained ventricular tachycardia inducibility and recurrence and prospectively evaluated the ability of the drug combination to prevent ventricular tachycardia recurrence when the arrhythmia remained inducible but was modified. BACKGROUND: Individual antiarrhythmic drugs are often ineffective in preventing the induction and recurrence of sustained ventricular tachycardia. Beta-adrenergic blockade and prolongation of refractoriness may be important components of successful antiarrhythmic therapy in patients with ventricular tachycardia. We reasoned that the combination of sotalol, which has beta-adrenergic blocking properties and prolonged ventricular refractoriness, and quinidine or procainamide, two agents that slow conduction and prolong refractory periods, would be effective therapy in such patients. METHODS: We administered low dose sotalol (205 +/- 84 mg/day) plus quinidine sulfate (1,278 +/- 479 mg/day) or procainamide (2,393 +/- 1,423 mg/day) to 50 patients with spontaneous sustained ventricular tachycardia or fibrillation and inducible ventricular tachycardia. RESULTS: In 21 (46%) of 46 patients, ventricular tachycardia was rendered noninducible at electrophysiologic study (group I), and in 17 patients (37%), inducible tachycardia was modified according to prospectively identified criteria (group II), for a combined 83% response rate. Ventricular refractory periods increased from 252 +/- 24 to 316 +/- 28 ms and from 265 +/- 33 to 316 +/- 24 ms in groups I and II, respectively (p < 0.001), but from 234 +/- 19 to only 286 +/- 13 ms in the group of patients with unmodified ventricular tachycardia inducibility (n = 8, group III, p < 0.001). Cycle length of induced ventricular tachycardia slowed from 324 +/- 62 to 432 +/- 70 ms in group II patients (p < 0.001), whereas it slowed less in group III patients (279 +/- 73 to 314 +/- 63 ms, p = NS). Forty-two of the 50 patients (including all patients in groups I and II) were discharged on treatment with the drug combination. After 25 +/- 19 months of follow-up, the actuarial recurrence rate of ventricular tachycardia was 6%, 6% and 11% at 1, 2 and 3 years, respectively. Among patients in whom this drug combination was unsuccessful at electrophysiologic study (group III) and in those who received alternative therapy after combination therapy was discontinued because of side effects, actuarial recurrence rates were 9%, 14% and 32% at 1, 2 and 3 years, respectively. CONCLUSIONS: The combination of sotalol plus quinidine or procainamide markedly prolongs ventricular refractoriness and slows induced ventricular tachycardia in a high proportion of patients. Patients with modified or noninducible tachycardia have a low rate of arrhythmia recurrence in follow up. This drug combination deserves further evaluation. PMID- 8509530 TI - Evaluation of a single-stage isoproterenol-tilt table test in patients with syncope. AB - OBJECTIVES: The purpose of this study was to compare clinical outcomes and tilt test variables between a single-stage tilt test with an infusion of 5 micrograms/min of isoproterenol and a conventional multistage test with infusions of 0, 2 and 5 micrograms/min of isoproterenol in three successive stages. BACKGROUND: The diagnosis of neuromediated syncope is often established with isoproterenol--head-up tilt table testing. Previous work has suggested that a single infusion of 5 micrograms/min of isoproterenol during 80 degrees head-up tilt for < or = 10 min should be sufficient to establish the diagnosis. METHODS: Forty patients with recurrent syncope underwent both tests in a randomized crossover fashion. RESULTS: Of 24 patients with positive findings on a multistage test, 19 (79%) had positive findings on a single-stage test, whereas 13 (81%) of 16 patients with negative results on a multistage test had negative results on a single-stage test (p < 0.001, chi-square analysis). Presyncope developed monoexponentially with time at similar rates in both tests, with half-times to presyncope of 1.3 and 2 min for the single-stage and multistage test, respectively. Intertest intrapatient times to presyncope correlated well (r = 0.74, p = 0.001). Finally, peak and trough heart rates each were similar and correlated well between tests. The mean peak heart rate was 136 +/- 25 and 133 +/ 18 beats/min for the single-stage and multistage test, respectively (p = NS, t test; r = 0.50, p = 0.002, linear regression). The mean trough heart rate was 76 +/- 31 and 78 +/- 36 beats/min for the single-stage and multistage test, respectively (p = NS, t test; r = 0.86, p < 0.001, linear regression analysis). CONCLUSIONS: The single-stage and multistage tilt tests are equivalent with regard to clinical outcome and tilt test variables, although the single-stage test is considerably less time-consuming. PMID- 8509531 TI - Transstenotic coronary pressure gradient measurement in humans: in vitro and in vivo evaluation of a new pressure monitoring angioplasty guide wire. AB - OBJECTIVES: The present study was designed to investigate 1) the feasibility and accuracy of coronary pressure measurements with a novel 0.015-in. (0.038 cm) fluid-filled guide wire, and 2) the effect of the guide wire itself on stenosis hemodynamics. BACKGROUND: To assess the functional results of coronary angioplasty, measurements of the transstenotic pressure gradient have been advocated. However, this gradient is no longer routinely measured because it is not reliable when determined with the angioplasty catheter. METHODS: A fluid filled 0.015-in. guide wire to be connected to a conventional pressure transducer was developed. Five wires were tested for their frequency response characteristics and for their accuracy in measuring hydrostatic pressure. In an in vitro model of stenosis (reference diameter 4 mm), the pressure gradient was determined at incremental flow levels for varying stenosis severity with and without a 0.015-in. guide wire through the narrowing. In 37 patients, the transstenotic pressure gradient was measured before and after angioplasty and compared with obstruction area and percent area stenosis as determined by quantitative coronary angiography. RESULTS: The correlation between the actual pressure and the pressure recorded by the guide wire was excellent (r = 0.98) despite a slight underestimation (-3 +/- 5%). Phasic pressure recordings were precluded by a long time constant of 16 +/- 4 s. The presence of the guide wire produced a significant overestimation (> 20%) of the pressure decrease only in cases of tight stenosis (> 90% area reduction). Furthermore, a theoretic model based on the fluid dynamic equation predicted that this overestimation was inversely proportional to the reference diameter of the vessel, yet was only slightly influenced by the flow. The lesion was crossed in all but one patient (97%) and pressure gradient was recorded throughout the study in 34 (94%) of 36 patients. The mean pressure gradient decreased from 30 +/- 19 before to 3 +/- 5 mm Hg after angioplasty (p < 0.01). A curvilinear relation was found between the pressure gradient and both percent area stenosis (r2 = 0.67) and obstruction area (r2 = 0.72). A sharp increase in pressure gradient was noted once the stenosis exceeded 75% area reduction. CONCLUSIONS: Mean transstenotic pressure gradients can be easily and reliably recorded with a 0.015-in. fluid-filled guide wire. This ability should facilitate the functional assessment of coronary stenoses of intermediate severity and of immediate postangioplasty results. PMID- 8509532 TI - Clinical applications of coronary sinus retroperfusion during high risk percutaneous transluminal coronary angioplasty. AB - OBJECTIVES: This study was designed to determine the efficacy of synchronized coronary sinus retroperfusion of arterial blood in reducing myocardial ischemia associated with the performance of high risk coronary angioplasty. BACKGROUND: Previous animal and clinical work has demonstrated the efficacy of this technique in supporting ischemic myocardium. METHODS: Twenty-one patients were randomized to alternately receive coronary sinus retroperfusion support during either the second or the third coronary angioplasty balloon inflation, after an initial unsupported brief control inflation. Myocardial ischemia was assessed by the extent of echocardiographic left ventricular wall motion abnormality, quantified ST segment deviation and hemodynamic and anginal variables during balloon inflations performed with and without coronary sinus retroperfusion support. Regional wall motion score was defined as hyperkinesia (-1), normokinesia (0), hypokinesia (+1), akinesia (+2) and dyskinesia (+3). RESULTS: A reduction in the echocardiographic left anterior descending regional wall motion score in retroperfusion-supported (1.7 +/- 2.1) versus unsupported (2.7 +/- 1.6) inflations (p < 0.05) was noted. Twelve-lead electrocardiographic monitoring revealed no additional ST segment deviation during supported (173 +/- 95 s) compared with unsupported (129 +/- 87 s) angioplasty inflations despite a significantly longer duration of supported inflations (p < 0.004). Mean and peak systolic coronary sinus pressures differed during supported inflations (21 +/- 6 and 44 +/- 13 mm Hg) versus unsupported inflations (10 +/- 4 and 16 +/- 5 mm Hg) (p < 0.001). There was no difference in hemodynamic or anginal variables. CONCLUSIONS: A reduction in ischemia as defined by wall motion abnormality during retroperfusion-supported compared with unsupported angioplasty balloon inflations was documented. No additional ST segment deviation occurred during retroperfusion supported compared with unsupported balloon inflations despite a significantly longer duration of supported inflations. No difference in hemodynamic or anginal variables was noted. PMID- 8509533 TI - Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes. AB - OBJECTIVES: This study reports on the initial experience with the Gianturco Roubin flexible coronary stent. The immediate and 6-month efficacy of the device and the incidence of the complications of death, myocardial infarction, emergency coronary artery bypass surgery and recurrent ischemic events are presented. BACKGROUND: Abrupt or threatened vessel closure after coronary angioplasty is associated with increased risk of myocardial infarction, emergency coronary artery bypass graft surgery and in-hospital death. When dissection or prolapse of dilated plaque into the lumen is unresponsive to additional or prolonged balloon catheter inflation, coronary stenting offers a nonsurgical mechanical means to rapidly restore stable vessel geometry and adequate coronary blood flow. METHODS: From September 1988 through June 1991, 518 patients underwent attempted coronary stenting with the 20-mm long Gianturco-Roubin coronary stent for acute or threatened vessel closure after angioplasty. In 494 patients, one or more stents were deployed. Thirty-two percent of patients received stents for acute closure and 69% for threatened closure. RESULTS: Successful deployment was achieved in 95.4% of patients. Overall, stenting resulted in an immediate angiographic improvement in the diameter stenosis from 63 +/- 25% before stenting to 15 +/- 14% after stenting. Emergency coronary artery bypass graft surgery was required in 4.3% (21 of 493 patients). The incidence of in-hospital myocardial infarction (Q wave and non-Q wave) was 5.5% (27 of 493 patients). At 6 months, myocardial infarction was infrequent, occurring in 1.6% (8 of 493 patients). The incidence of in-hospital death was 2.2% (11 of 493 patients). Late death occurred in 7 patients (1.4%) and 34 patients (6.9%) required later bypass graft surgery. Complications included blood loss, primarily from the arterial access site, and subacute thrombosis of the stented vessel in 43 patients (8.7%). CONCLUSIONS: The early multicenter experience suggests that this stent is a useful adjunct to coronary angioplasty to prevent or minimize complications associated with flow limiting coronary artery dissections previously correctable only by surgery. Although this study was not randomized, it demonstrated a high technical success rate and encouraging results with respect to the low incidence of emergency coronary artery bypass graft surgery and myocardial infarction. PMID- 8509534 TI - Correlation of basal coronary artery tone with constrictive response to ergonovine in patients with variant angina. AB - OBJECTIVES: This study was conducted to examine whether basal coronary artery tone is elevated at the spastic site in patients with variant angina and to determine the significance of basal artery tone in predicting provocation of coronary artery spasm. BACKGROUND: Previous data have been conflicting on whether basal coronary artery tone is elevated in patients with variant angina. METHODS: We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin in 20 patients with variant angina and 24 control subjects. We also examined the correlation between basal coronary artery tone and the constrictive response to ergonovine. RESULTS: In the patients with variant angina in whom spasm was provoked by the lower doses (1 or 5 micrograms) of ergonovine, basal coronary artery tone was greater (p < 0.05) at the spastic site (54 +/- 15% or 36 +/- 16%, respectively) than at the nonspastic site (40 +/- 25% or 25 +/- 15%, respectively). Basal coronary tone at the nonspastic site in these patients was greater (p < 0.01) than that in control subjects (15 +/- 6%). In the patients with variant angina in whom spasm was provoked only by the higher doses (15 or 50 micrograms) of ergonovine, basal coronary artery tone was comparable at the spastic and nonspastic sites and was not different from that in control subjects. The diagnostic sensitivity and specificity of elevated basal coronary artery tone (> or = 40%) in predicting provocation of spasm were 26% and 98%, respectively. CONCLUSIONS: These results indicate that elevated basal coronary artery tone may be useful in predicting provocation of coronary spasm, but the normal level of basal coronary artery tone does not exclude such provocation. PMID- 8509535 TI - 24th Bethesda conference: Cardiac transplantation. Task Force 2: Donor guidelines. PMID- 8509536 TI - Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation. AB - OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10( 7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients. PMID- 8509537 TI - Optimal use of dobutamine stress for the detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both? AB - OBJECTIVES: This study was conducted to examine the efficacy of dobutamine stress two-dimensional echocardiography and perfusion scintigraphy for the detection of coronary artery disease in routine practice, to establish the causes of erroneous results and to derive appropriate criteria for the selection of either or both tests. BACKGROUND: Dobutamine stress combined with echocardiography or perfusion scintigraphy may be used to detect coronary artery disease. Although both imaging approaches have demonstrated similar levels of accuracy, it is not known whether there may be particular indications for the use of one or the other technique or a rationale for their combination. METHODS: Two hundred seventeen patients without previous infarction were studied prospectively with dobutamine stress echocardiography and technetium-99m methoxy isobutyl nitrile (sestamibi) single photon emission computed tomography at the time of diagnostic coronary angiography. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or stress-induced abnormalities of perfusion and regional function. The extent of these abnormalities was correlated with an equivalent score of extent of angiographic disease. RESULTS: Significant coronary artery disease was found in 142 patients; 102 (72%) were identified by dobutamine echocardiography and 108 (76%, p = NS) by perfusion imaging. In 75 patients without significant disease, the specificity of dobutamine echocardiography was 83% compared with 67% for scintigraphy (p = 0.05). Echocardiographic sensitivity was lower in patients unable to complete the test because of side effects (n = 64) than in the remainder (59% vs. 77%, p = 0.02); this influence was less apparent with scintigraphy (71% vs. 78%, p = NS). Selective use of scintigraphy in the 31 patients with a negative submaximal stress echocardiogram led to a sensitivity of 80% for this combination. Patients with left ventricular hypertrophy accounted for most of the difference in specificity between echocardiography and scintigraphy (94% vs. 59%, p = 0.02). Their respective accuracies were 76% and 73%. CONCLUSIONS: Dobutamine stress echocardiography and perfusion scintigraphy have equivalent accuracy. In patients with left ventricular hypertrophy, echocardiography appears to be the test of choice. Selective use of sestamibi scintigraphy in patients with a negative submaximal echocardiogram enhances the accuracy of stress echocardiography alone. PMID- 8509538 TI - Measurement variables for optimal performance of the ST integral. AB - OBJECTIVES: This study examined the effect of varied onset and offset of ST measurement on performance of the ST integral for the detection of coronary artery disease. BACKGROUND: The J point and other early ST segment measurements may significantly reduce the accuracy of ST segment depression criteria. METHODS: The exercise electrocardiograms (ECGs) from 112 normal subjects and 163 patients with known or likely coronary disease were analyzed, using the J point or 20 ms after the J point onset and 60 or 80 ms after the J point offset of ST integral calculation. RESULTS: At a matched specificity of 97%, incorporation of J point measurements into the ST integral significantly reduced test performance. The ST integrals measured from the J point to 80 and to 60 ms after the J point were significantly less sensitive (31% and 25%, respectively) than those measured from 20 to 80 ms and 20 to 60 ms after the J point (39% and 31%, p < 0.001 and p < 0.01, respectively). For either J point or 20 ms after the J point onset of the ST integral measurement, the sensitivity was higher using 80 ms than 60 ms after the J point offset (31% vs. 25%, p < 0.01 and 39% vs. 31%, respectively, p < 0.001). Comparison of areas under receiver operating characteristic curves confirmed the superior performance of the ST integral measured from 20 to 80 ms after the J point relative to the other measurement intervals. CONCLUSIONS: These findings demonstrate that J point and early repolarization phase time-voltage measurements reduce performance of the ST integral for the identification of coronary artery disease and provide further evidence that optimal signal to noise content of repolarization for the identification of ischemia can be localized to later phases of the ST segment. PMID- 8509539 TI - Nomogram based on metabolic equivalents and age for assessing aerobic exercise capacity in men. AB - OBJECTIVES: The goal of this study was to create a nomogram, based on maximal exercise capacity (in metabolic equivalents [METs]) and age, for assessing a patient's ability to perform dynamic exercise to quantify the level of physical disability or relative capacity for physical activity. BACKGROUND: Providing an estimation of exercise capacity relative to age is clinically useful. Such an estimate can be derived from measured or estimated maximal oxygen uptake (in METs) from treadmill exercise testing and age. It is an effective means of communicating to patients their cardiopulmonary status, encouraging improvement in exercise capacity and quantifying disability. METHODS: Exercise test results of 1,388 male patients (mean age 57 years, range 21 to 89) free of apparent heart disease who were referred for exercise testing for clinical reasons were retrospectively reviewed. This referral group as well as subgroups of active (n = 346) and sedentary (n = 253) patients were analyzed to determine norms for age and for age by decades for exercise test responses, including METs, maximal heart rate and maximal systolic blood pressure. Regression equations were calculated from this information, and a nomogram for calculating degree of exercise capacity from age and MET level achieved by a patient was created. A similar analysis was performed in a separate group of 244 apparently healthy, normal male volunteers (mean age 45 +/- 14 years, range 18 to 72) who underwent exercise testing with direct measurement of expired gases. RESULTS: Equations for predicted METs for age were derived for the entire clinical referral group (METs = 18.0-0.15[Age]) and for the subgroups of active (METs = 18.7-0.15[Age]) and sedentary (METs = 16.6-0.16[Age]) patients. All results achieved statistical significance, with p values < 0.001. In the volunteer group of normal men who performed exercise testing with ventilatory gas exchange, the decline in maximal heart rate and METs with age was not as steep as in the referral group. Although the normal group confirmed nomograms published previously among similar subjects, the equations derived from the patients differed from those previously reported; in contrast to previous studies using healthy volunteers, the equations and nomograms for the referral group are more appropriate for patients typically referred for testing in a hospital or office-based internal medicine practice. CONCLUSIONS: Norms for METs based on age are presented as well as population-specific nomograms that enable physicians to assess patients' exercise capacity relative to their age group. PMID- 8509540 TI - Outcomes in critically ill neonates with pulmonary stenosis and intact ventricular septum: a multiinstitutional study. Congenital Heart Surgeons Society. AB - OBJECTIVE: This study attempted to determine the optimal therapeutic interventions by risk-adjusted comparisons of early and intermediate-term outcomes. BACKGROUND: The variety of interventions and the small case load at individual institutions have delayed the generation of reliable information concerning therapy for this condition. METHODS: In this prospective 27 institution study, 101 neonates were consecutively enrolled (between January 1, 1987 and January 1, 1991). Treatment was determined by the physicians. Demographic and morphologic details were tabulated. Dimensions of the pulmonary "anulus" and tricuspid anulus were measured on echocardiograms, and right ventricular cavity size was estimated. Right ventricular-pulmonary trunk pressure gradients were tabulated. Numerous analyses were made. RESULTS: Severe pulmonary valve stenosis and an intact ventricular septum were present in all patients. The right ventricular-pulmonary trunk junction ("anulus") was severely narrowed in 15%. Right ventricular cavity size was severely reduced in 4%. The tricuspid valve was small in 15% of patients; its diameter was poorly correlated with right ventricular cavity size. Eighty-nine percent and 81% of patients survived > or = 1 month and 4 years, respectively, after the initial procedure. Multivariable analysis identified no patient-specific risk factors for death. Only open pulmonary valvotomy without a support technique was uniformly a procedural risk factor; under some circumstances, transannular patching without a shunt was a risk factor. The right ventricular-pulmonary trunk gradient immediately after valvotomy was < 30 mm Hg in 81% of patients and was similar after surgical and balloon valvotomy. In 74% of patients, no intervention was required after the first accomplished intervention. CONCLUSIONS: Marked variation in morphology is uncommon in critical pulmonary stenosis in neonates. Percutaneous balloon valvotomy and certain types of surgical valvotomy are optimal initial procedures. The unusual situation of a small pulmonary "anulus" may initially require a transannular patch and a systemic-pulmonary artery shunt. PMID- 8509541 TI - Anatomic correction of transposition of the great arteries in neonates. AB - OBJECTIVES: This retrospective study attempts to assess the results of the neonatal anatomic repair of transposition of the great arteries by a single institution. BACKGROUND: Anatomic correction of transposition of the great arteries by means of the arterial switch operation is now widely accepted as the therapeutic method of choice. METHODS: Four hundred thirty-two consecutive neonates underwent an arterial switch operation for various forms of transposition of the great arteries. There were 362 neonates with transposition and intact ventricular septum, 47 with a ventricular septal defect, 6 with intact ventricular septum and coarctation of the aorta and 17 with ventricular septal defect and coarctation. Among patients with coarctation, 18 underwent a single stage repair through median sternotomy. The mean age was 13.1 +/- 4.2 days. Coronary artery distribution was described according to the origin and initial course of the arteries. RESULTS: Overall in-hospital mortality was 7.8% (34 patients) and was 7.6% for transposition with intact ventricular septum, 8.5% for transposition with ventricular septal defect and 13.3% for transposition with ventricular septal defect and coarctation. Univariate analysis of risk factors revealed that coronary anatomy was the main determinant for operative survival. A mean follow-up time of 44 +/- 19 months was achieved in all but five survivors. More than 95% were in New York Heart Association functional class I, without medication and with normal left ventricular function. Reoperation was performed in 20 patients: early reoperation (< 30 days) in 4 and late reoperation in 16. Actuarial survival rates at 5 years were 91.3% (transposition with intact ventricular septum) and 81.06% (transposition with ventricular septal defect). As well, freedom from reoperation at 5 years was 96.8% (transposition with intact ventricular septum) and 84.6% (transposition with ventricular septal defect). CONCLUSIONS: The arterial switch operation is feasible in almost all forms of transposition of the great arteries in neonates as primary and definitive repair. Palliative surgery is recommended in cases with complex intracardiac anatomy not amenable to early repair. PMID- 8509542 TI - Individual pulmonary vein size and survival in infants with totally anomalous pulmonary venous connection. AB - OBJECTIVES: We investigated whether mortality in totally anomalous pulmonary venous connection could be predicted from preoperative individual pulmonary vein size. BACKGROUND: Some infants with this anomaly die with or without surgical repair because of stenosis of individual pulmonary veins. METHODS: Individual pulmonary vein, vertical vein and pulmonary venous confluence diameters were retrospectively measured from preoperative echocardiograms in 32 infants with totally anomalous pulmonary venous connection presenting to Children's Hospital, Boston over a 4 1/2-year period. Data on body surface area, other cardiac anomalies, presence of initial pulmonary venous obstruction and early surgery and outcome were also recorded. RESULTS: Of 32 patients, 6 (18.8%) died before hospital discharge, and 8 (25.0%) died subsequently. Six (75.0%) of the eight patients who died late had individual pulmonary vein stenosis at sites remote from the surgical anastomosis to the left atrium. The remaining 18 patients (56.3%) are alive at a mean follow-up period of 9.7 months. A Cox proportional hazards model revealed that small sum of individual pulmonary vein diameters (p = 0.0004), small confluence size (p = 0.02) and presence of heterotaxy syndrome (p = 0.008) were each significant univariate predictors of survival. Multivariate analysis showed that small pulmonary vein sum was a strong predictor of survival (p = 0.008), independent of the presence of heterotaxy syndrome. An analysis stratified by the presence of heterotaxy syndrome showed that the predictive effect of small pulmonary vein sum on survival was strongest in patients without heterotaxy syndrome. CONCLUSIONS: These data show that individual pulmonary vein size at diagnosis is a strong, independent predictor of survival in patients with totally anomalous pulmonary venous connection. In patients with this anomaly and small individual pulmonary veins, the anomaly may not be correctable by surgical creation of an anastomosis between the pulmonary venous confluence and the left atrium. PMID- 8509543 TI - Prevalence and risk factors for aortopulmonary collateral vessels after Fontan and bidirectional Glenn procedures. AB - OBJECTIVES: The purpose of this study was to evaluate the prevalence of and risk factors for aortopulmonary collateral vessels in patients who have undergone a bidirectional Glenn or Fontan procedure, or both. BACKGROUND: Aortopulmonary collateral vessels are frequently observed angiographically in patients after a bidirectional Glenn or Fontan procedure. These vessels may provide a source of pulmonary blood flow competitive with anterograde cavopulmonary flow. METHODS: We performed a retrospective study of all patients (n = 196) who underwent catheterization between January 1, 1988 and February 29, 1992 (n = 268) after bidirectional Glenn or Fontan procedures and reviewed clinical, hemodynamic and angiographic phone data. RESULTS: Collateral vessels were diagnosed in 36% of patients. Patients who underwent the bidirectional Glenn procedure were more likely to have collateral vessels than patients who underwent the Fontan procedure (65% vs. 30%, respectively; p < 0.0001). Patients with a history of a Blalock-Taussig shunt were more likely to have collateral vessels than those without (50% vs. 24%, respectively; p = 0.0006). Discretely identifiable collateral vessels were measurable in 54 (20%) of 268 catheterizations. The total estimated cross-sectional area of these vessels averaged 10.7 +/- 7.2 mm2. In patients who underwent the bidirectional Glenn procedure, a step-up in oxygen saturation from the superior vena cava to the distal pulmonary arteries or an upper lobe filling defect, or both, on pulmonary angiogram predicted total estimated cross-sectional area of collateral vessels. Most collateral vessels originated from the internal mammary arteries (34%) and the thyrocervical trunks (22%). Only 9% of collateral vessels arising from the brachiocephalic vessels were visualized by aortogram; the remainder required selective angiography in the subclavian or more distal arteries. CONCLUSIONS: Aortopulmonary collateral vessels are common after bidirectional Glenn and Fontan procedures. Aortograms often fail to diagnose their presence. The left to right shunt carried by these vessels is associated with a step-up in oxygen saturation in the distal pulmonary arteries. The clinical significance and indications for closure of these vessels are not known. PMID- 8509544 TI - 24th Bethesda conference: Cardiac transplantation. Task Force 3: Recipient guidelines/prioritization. PMID- 8509545 TI - Atrial ejection force: a noninvasive assessment of atrial systolic function. AB - OBJECTIVES: The purpose of this study was to define atrial ejection force and to develop a method for its noninvasive measurement from echocardiographic data. BACKGROUND: Assessment of diastolic function through measurement of the components of ventricular filling has largely neglected the vigor of atrial systole, in part because this has been difficult to quantify. However, atrial ejection force, defined as that force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, can be assessed noninvasively by combined two-dimensional imaging and Doppler echocardiography. This index of atrial function, based on classic newtonian mechanics, provides a physiologic assessment of atrial systolic function. METHODS: To evaluate the usefulness of atrial ejection force, we studied the return of left atrial ejection force in 29 patients after elective cardioversion for atrial fibrillation. Transmitral Doppler inflow patterns at rest were assessed immediately after cardioversion and at 24 h, 1 week, 1 month and > 3 months later. A healthy adult group (n = 10) served as control subjects. RESULTS: After successful cardioversion, atrial ejection force was significantly depressed compared with that in the control group (5.2 +/- 6.8 vs. 16.3 +/- 4.7 kdynes; p < 0.0001). Over successive weeks, atrial ejection force improved in the subgroup of patients who remained in sinus rhythm (n = 18), whereas no improvement was seen during the period of maintained sinus rhythm in the patients with subsequent reversion to atrial fibrillation (n = 11). CONCLUSIONS: Atrial ejection force provides a physiologic assessment of atrial systolic function and is a potentially useful index for assessing atrial contribution to diastolic performance. In patients who successfully underwent cardioversion from atrial fibrillation, atrial ejection force improved over several weeks only in the subgroup in which sinus rhythm was maintained. PMID- 8509546 TI - Clinical, electrocardiographic and morphologic features of massive fatty deposits ("lipomatous hypertrophy") in the atrial septum. AB - OBJECTIVES: This study examined the morphologic features and the clinical significance of massive fatty deposits in the atrial septum of the heart. BACKGROUND: Large deposits of adipose tissue in the atrial septum were first described in 1964 and have been referred to as "lipomatous hypertrophy" of the atrial septum. A relation between these fatty deposits and atrial arrhythmias has been suggested. METHODS: The thickness of the atrial septum cephalad to the fossa ovalis ranged from 1.5 to 6 cm in 91 patients and was > or = 2 cm in 80 patients. This report focuses primarily on the latter 80 patients. RESULTS: The thickness of the atrial septum in the 80 patients correlated with body weight and the thickness of the adipose tissue in the atrioventricular groove and that covering the right ventricle. In 53 patients (67%), one or more of the four major epicardial coronary arteries were narrowed > 75% in cross-sectional area by atherosclerotic plaque. Atrial arrhythmias were present in 31 patients (40%). Patients with larger deposits of fat (atrial septal thickness > or = 3 cm) had a higher frequency of atrial arrhythmias (60% vs. 34%, p < 0.01). The atrial septum was significantly thicker in patients with atrial arrhythmia compared with those without atrial arrhythmias (2.9 vs. 2.3 cm, p < 0.01). Of the 28 patients with available electrocardiograms, 20 (71%) showed atrial arrhythmias (nine atrial premature complexes, seven atrial fibrillation, three atrial tachycardia, one ectopic atrial rhythm and one junctional rhythm). CONCLUSIONS: Massive fatty deposits in the atrial septum are associated with large deposits of fat elsewhere in the body and other parts of the heart. They are frequently associated with atrial arrhythmias and atherosclerotic coronary artery disease. PMID- 8509547 TI - Impaired left ventricular contractile function in patients with long-term mitral regurgitation and normal ejection fraction. AB - OBJECTIVES: We tested the hypotheses that left ventricular chamber elastance would detect impaired contractile function in patients with long-term mitral regurgitation and a normal ejection fraction and that these patients would have unique temporal left ventricular size and ejection fraction responses to mitral valve surgery. BACKGROUND: Although it has been suggested that left ventricular contractile function may begin deteriorating in patients with long-term mitral regurgitation whereas ejection fraction remains normal, no data exist in humans. METHODS: We studied 11 control patients and 28 patients with long-term mitral regurgitation using micromanometer-measured pressures, biplane contrast cineventriculography and radionuclide angiography under control conditions and with alterations in load during right atrial pacing to calculate left ventricular chamber elastance and myocardial stiffness. RESULTS: The patients with mitral regurgitation were classified into subgroups: Group I, normal contractile function; Group II, impaired contractile function (reduced Emax) but normal ejection fraction, and Group III, impaired contractile function (reduced Emax) with reduced systolic myocardial stiffness. Twenty-two of the patients with mitral regurgitation underwent mitral valve surgery. In Group I, comparable decreases in left ventricular volume indexes (p < 0.01 and p = 0.05, respectively) were associated with no change in ejection fraction at 3 months and 1 year. In contrast, in Group II, reductions in volume indexes (p < 0.0001 and p < 0.001) were associated with a short-term decrease in ejection fraction (p < 0.001) that recovered at 1 year (p < 0.01 vs. short-term). Finally, in Group III, variable responses in volume indexes were associated with a consistent decrease in ejection fraction at 3 months and 1 year. CONCLUSIONS: An analysis of left ventricular chamber elastance provides data to support the concepts that 1) contractile function is impaired in some patients with long-term mitral regurgitation and a normal ejection fraction, 2) impaired contractile function may not be irreversible in all of these patients, and 3) an earlier consideration of mitral valve surgery may be warranted to preserve contractile function in these patients. PMID- 8509548 TI - Bolus intravenous nitroglycerin predominantly reduces afterload in patients with excessive arterial elastance. AB - OBJECTIVES: We hypothesized that bolus intravenous nitroglycerin would be an afterload-reducing agent in patients with excessive initial afterload for their level of left ventricular systolic function. Conversely, bolus intravenous nitroglycerin should be a preload-reducing agent in patients without excessive initial afterload. BACKGROUND: Although nitroglycerin has both preload- and afterload-reducing actions, methods to predict its predominant site of action in an individual patient have not been previously described. METHODS: Left ventricular pressure-volume relations were recorded with micromanometer and conductance catheters during bolus injection of intravenous nitroglycerin in 27 patients with both normal left ventricular systolic function and varying degrees of congestive heart failure. Preload was determined by end-diastolic volume, afterload by effective arterial elastance, left ventricular systolic function by end-systolic elastance and coupling of afterload and ventricular function by the ratio of effective arterial elastance to end-systolic elastance (Ea/Ees ratio). An Ea/Ees ratio > 1 was defined as excessive afterload for the level of ventricular function. RESULTS: Patients with an initial Ea/Ees ratio < 1 (Group 1) constituted a group of normotensive patients with intact ventricular function who exhibited a predominant reduction in preload in response to intravenous nitroglycerin. Those with an initial Ea/Ees ratio > 1 and normal or mildly depressed ventricular function (Group 2a) constituted a group of patients, most of whom were hypertensive, who exhibited a predominant afterload reduction. Finally, those with an initial Ea/Ees ratio > 1 and abnormal ventricular function (Group 2b) constituted a group of patients with clinical congestive heart failure who exhibited both preload and afterload reduction but a predominant afterload reduction because stroke volume increased. CONCLUSIONS: Patients with normal arterial elastance and ventricular function respond to nitroglycerin with a predominant preload reduction, whereas patients with either excessive arterial elastance or abnormal ventricular function respond with a predominant afterload reduction. PMID- 8509549 TI - Left ventricular volume and endocardial surface area by three-dimensional echocardiography: comparison with two-dimensional echocardiography and nuclear magnetic resonance imaging in normal subjects. AB - OBJECTIVES: We evaluated a three-dimensional echocardiographic method for ventricular volume and surface area determination that uses polyhedral surface reconstruction. Six to eight nonparallel, unequally spaced, nonintersecting short axis planes were positioned with a line of intersection display to overcome limitations associated with two-dimensional echocardiography. BACKGROUND: Two dimensional echocardiographic methods of ventricular volume and surface area determination are limited by assumptions about ventricular shape and image plane position. METHODS: Left ventricular end-diastolic and end-systolic volumes and endocardial surface areas determined by three-dimensional echocardiography and nuclear magnetic resonance (NMR) imaging were compared in 15 normal subjects (7 men, 8 women, aged 23 to 41 years, body surface area 1.38 to 2.17 m2). Ten of these subjects also underwent two-dimensional echocardiography; and end-diastolic and end-systolic volumes were determined by the apical biplane summation of discs method and compared with results of NMR imaging. RESULTS: Interobserver variability was 5% to 8% for three-dimensional echocardiography and 6% to 9% for NMR imaging. Both methods were in close agreement on end-diastolic volume (r = 0.92, SEE = 6.99 ml) and end-systolic volume (r = 0.81, SEE = 4.01 ml) and on end diastolic surface area (r = 0.84, SEE = 8.25 cm2) and end-systolic surface area (r = 0.84, SEE = 4.89 cm2). Three-dimensional echocardiography and NMR imaging correlated significantly better for end-diastolic volume (r = 0.90, SEE = 7.0 ml) and end-systolic volume (r = 0.88, SEE = 3.1 ml) than did two-dimensional echocardiography and NMR imaging (r = 0.48, SEE = 20.5 ml for end-diastolic volume; r = 0.70, SEE = 5.6 ml for end-systolic volume). CONCLUSIONS: Three dimensional echocardiography is an in vivo method of measuring left ventricular end-diastolic and end-systolic volumes and endocardial surface area with results comparable to those of NMR imaging. Additionally, three-dimensional echocardiography is superior to the two-dimensional echocardiographic apical biplane summation method because the technique eliminates geometric assumptions and image plane positioning error. PMID- 8509550 TI - Influence of cardiac motion on Doppler measurements using in vitro and in vivo models. AB - OBJECTIVES: Using both in vitro and in vivo techniques, we investigated the extent to which cardiac motion alters Doppler-measured blood flow velocity and thus potentially can alter the calculation of valve areas or pressure gradients. BACKGROUND: Blood flow velocity measured by Doppler ultrasound represents the net motion of the blood relative to the transducer. It is widely assumed that the measured velocity represents the actual flow. It has been demonstrated that cardiac motion generates regularly occurring low velocity Doppler signals that are commonly treated as artifact. METHODS: We used an in vitro model that allowed us to measure and independently control the flow of a liquid through a chamber and the motion of the chamber relative to the Doppler beam. A cornstarch-water slurry was driven by a pulsatile pump through tubing to simulate the blood flow within the heart, and the tubing was cyclically moved by a piston to simulate the heart motion. We also measured cardiac motion using M-mode and two-dimensional echocardiography and compared the results with the Doppler signal derived from cardiac motion in subjects without cardiac disease. RESULTS: In the in vitro model, alteration in the motion of the tubing resulted in apparent changes in the measured maximal velocity of the fluid. The Doppler spectrum of the combined motion of the tubing and the fluid was the algebraic sum of their Doppler signals. In human subjects, the maximal slope of the M-mode tracing of the aortic annular motion and the peak Doppler signal due to cardiac motion were compared and were highly correlated. CONCLUSIONS: Cardiac motion alters the Doppler signal derived from blood flow. This effect can be demonstrated in vitro and in vivo. PMID- 8509551 TI - Calculation of volume flow rate by the proximal isovelocity surface area method: simplified approach using color Doppler zero baseline shift. AB - OBJECTIVES: The goal of this study was to develop an accurate, simplified proximal isovelocity surface area (PISA) method for calculating volume flow rate using lower blue-red interface velocity produced by a color Doppler zero baseline shift technique. BACKGROUND: The Doppler color proximal isovelocity surface area method has been shown to be accurate for calculating the volume flow rate (Q) across a narrowed orifice by the formula Q = PISA x Blue-red interface velocity. A hemispheric model is generally used to calculate proximal isovelocity surface area (PISA = 2 pi a2, where a = the radius corresponding to the blue-red interface velocity). Although a hemispheric model is simple, requiring measurement of one radius, it may underestimate the actual volume flow rate because, in the general case, the shape of a proximal isovelocity surface area is hemielliptic. Although a hemielliptic model is generally more accurate for calculating proximal isovelocity surface area, it is more complex, requiring measurement of two orthogonal radii. METHODS: Sixteen in vitro constant flow model studies were performed using planar circular orifices (diameter range 6 to 16 mm). The blue-red interface velocity was changed from 3 to 54 cm/s using color Doppler zero baseline shift. RESULTS: 1) With decreasing blue-red interface velocity, the size of the proximal isovelocity surface area was increased, and its shape changed from hemielliptic to hemispheric. 2) With the blue-red interface velocity in the range 11 to 15 cm/s, the proximal isovelocity surface area became nearly hemispheric; however, it was difficult to determine the blue red interface radius at a blue-red interface velocity < 10 cm/s because of interface fluctuations. 3) Calculated volume flow rate using the hemispheric proximal isovelocity surface area model with a single radius was relatively accurate at a blue-red interface velocity of 11 to 15 cm/s (mean percent difference from actual volume flow rate was -3.6%). CONCLUSIONS: Because the shape of the proximal isovelocity surface area is nearly hemispheric at a blue red interface velocity of 11 to 15 cm/s, volume flow rate can be accurately calculated in this proximal isovelocity surface area interface velocity range (produced by zero baseline shift) by measuring a single-interface radius. This approach should be clinically useful for calculating the volume flow rate across stenotic and regurgitant valves and across shunt defects. PMID- 8509552 TI - Pharmacologic modulation of the autonomic nervous system in the prevention of sudden cardiac death. A study with propranolol, methacholine and oxotremorine in conscious dogs with a healed myocardial infarction. AB - OBJECTIVES: The goal of the present study was to evaluate the antifibrillatory and hemodynamic effects of pharmacologic muscarinic activation and to compare them with those of beta-adrenergic blockade. BACKGROUND: Recent studies suggest a correlation between increased vagal activity and a reduced incidence of sudden cardiac death. Electrical stimulation of the vagus nerve reduces the incidence of ventricular fibrillation in a conscious animal model of sudden cardiac death. METHODS: Eleven dogs with healed anterior myocardial infarction, in which a 2-min left circumflex coronary artery occlusion during exercise caused ventricular fibrillation, were studied. They underwent subsequent tests with saline solution, propranolol (1 mg/kg body weight), methacholine (0.5 microgram/kg per min) and oxotremorine (8 micrograms/kg). RESULTS: In the test with saline solution, 100% of the dogs developed ventricular fibrillation; this occurred in only 10% of the tests with propranolol (95% confidence interval 0.2% to 44%; p < 0.001), 60% of the tests with methacholine (95% confidence interval 26% to 88%, p = 0.05) and 37.5% of the tests with oxotremorine (95% confidence interval 8% to 75%, p = 0.005). Propranolol and oxotremorine significantly reduced heart rate compared with saline solution, whereas methacholine did not. Propranolol significantly reduced maximal first derivative of left ventricular pressure, (dP/dtmax), particularly during myocardial ischemia, compared with the other treatments (2,391 +/- 582 mm Hg/s [mean +/- 1 SD] with propranolol vs. 4,226 +/- 1,237, 4,922 +/- 584 and 4,358 +/- 1,109 mm Hg/s with saline solution, methacholine and oxotremorine, respectively, p < 0.005). CONCLUSIONS: Propranolol was extremely effective against ventricular fibrillation. Methacholine and oxotremorine provided a significant, although less marked, protection and caused much less impairment of contractility compared with propranolol. Muscarinic receptor activation may represent a new approach to prevention of sudden cardiac death, particularly when beta-blockers are contraindicated and negative inotropic effects are to be avoided. PMID- 8509553 TI - Inhibitory effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury in hypercholesterolemic miniature pigs. AB - OBJECTIVES: The present study aimed to clarify the effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury. BACKGROUND: The mechanisms of coronary artery vasoconstriction after coronary angioplasty are not well understood. METHODS: After being fed a cholesterol-rich diet for 1 month, 71 Gottingen miniature pigs were randomly allotted to five groups: 16 pigs with no pretreatment (group A); 21 pigs pretreated with heparin, 3,000 U (group B); 13 pigs pretreated with aspirin, 50 mg/day orally for 2 days (group C); 11 pigs pretreated with ketanserin, 1 mg/kg body weight (group D); 10 pigs pretreated with aspirin, 50 mg/day for 2 days, heparin, 6,000 U and ketanserin, 1 mg/kg (group E). After this pretreatment, the left anterior descending or the left circumflex coronary artery, or both, was denuded by a 2F balloon catheter. RESULTS: The coronary vasoconstriction at the injured sites reached a peak level 6 min after the arterial injury and subsided within 30 min. The coronary vasoconstriction at the injured site 6 min after arterial injury was 56 +/- 5% in group A, which was significantly greater than that in group B (28 +/ 6%, p < 0.01), group C (25 +/- 5%, p < 0.01), group D (26 +/- 7%, p < 0.01) or group E (24 +/- 5%, p < 0.01), whereas there was no significant difference in the coronary vasoconstriction among the latter four groups. CONCLUSION: These results suggest that serotonin released from aggregating platelets plays a major part in the platelet-dependent coronary artery vasoconstriction after arterial injury. PMID- 8509554 TI - Maintenance of patency after thrombolysis in stenotic coronary arteries requires combined inhibition of thrombin and platelets. AB - OBJECTIVES: This study was designed to determine whether maintenance of patency in coronary arteries with high grade stenosis after thrombolysis with tissue-type plasminogen activator requires inhibition of thrombin or platelets, or both. BACKGROUND: Activation of both thrombin and platelets has been implicated in delaying coronary recanalization induced with fibrinolytic drugs and in predisposing to reocclusion. METHODS: Hirudin (1.5 mg/kg body weight) or aspirin (5 mg/kg), or both, was given conjunctively with tissue-type plasminogen activator in 28 conscious dogs with coronary thrombosis induced by electrical stimulation of the vessel wall in the presence of a previously placed high grade distal stenosis (85 +/- 12% [SEM] area reduction). RESULTS: Among 22 dogs exhibiting coronary recanalization, hirudin plus aspirin, but neither agent alone, modestly shortened the interval to recanalization (31 +/- 4 min with saline solution, n = 6; 29 +/- 4 min with aspirin, n = 5; 23 +/- 9 min with hirudin, n = 6; 21 +/- 7 min with hirudin+aspirin, n = 5). Reocclusion occurred promptly and persisted in five of six dogs given only saline solution plus tissue type plasminogen activator, in four of six dogs given hirudin and five of five dogs given aspirin; however, reocclusion was prevented in all five of the dogs given both hirudin and aspirin with tissue-type plasminogen activator (p < 0.05 compared with saline-treated dogs). In dogs given both hirudin and aspirin, the partial thromboplastin time was 2.4 +/- 0.3 times baseline, and the template bleeding time was prolonged only modestly (1.6 +/- 0.3 times baseline). CONCLUSIONS: Thus, the combination of hirudin and aspirin in doses that do not markedly perturb hemostasis prevents early reocclusion after thrombolysis despite the presence of severe stenosis. Accordingly, conjunctive administration of both anti-thrombin and antiplatelet agents appears to be necessary for optimal maintenance of patency after thrombolysis induced in the presence of high grade coronary stenosis. PMID- 8509555 TI - Laser-mediated transmural myocardial channels do not salvage acutely ischemic myocardium. AB - OBJECTIVES: We sought to determine whether the presence of transmural laser-made channels could provide blood flow to ischemic myocardium. BACKGROUND: Laser-made transmural channels have been used in patients to restore blood flow to ischemic myocardium. Whether such channels actually relieve ischemia is unclear. We therefore tested the concept in an animal model of acute ischemia. METHODS: Eighteen dogs underwent 6 h of permanent coronary artery occlusion. At 30 min after occlusion, 8 dogs were randomized to the laser-treated group (30 to 40 transmural channels, 1 mm in diameter, were made in the cyanotic area using a holmium: yttrium-aluminum-garnet laser), and 10 were randomized to the control group (no treatment). Transmural blood flow was measured before and after treatment using radiolabeled microspheres. Regional segment shortening and myocardial lactate content were measured in four of the control and two of the laser-treated dogs. Infarct size was measured in all animals using triphenyltetrazolium chloride staining. RESULTS: Laser channels failed to increase blood flow to ischemic tissue. After laser channels were made, mean transmural flow averaged 0.10 +/- 0.03 versus 0.11 +/- 0.03 ml/min per g in treated versus control dogs, respectively. Furthermore, infarct size was similar in both groups (46 +/- 6% vs. 43 +/- 7%, respectively, of the myocardium at risk, p = NS). In addition, the presence of laser channels neither improved regional myocardial function nor enhanced washout of accumulated lactate. CONCLUSIONS: Direct laser revascularization of the heart did not provide any immediate benefit to ischemic myocardium in this canine model of coronary artery occlusion. Thus, it is doubtful that direct laser-mediated myocardial revascularization would be of immediate benefit in the treatment of patients with acute ischemia. PMID- 8509556 TI - 24th Bethesda conference: Cardiac transplantation. Task Force 4: Function of the heart transplant recipient. PMID- 8509558 TI - Diastolic failure: pathophysiology and therapeutic implications. AB - Primary diastolic dysfunction or failure is a distinct pathophysiologic entity. It results from increased resistance to ventricular filling, which leads to an inappropriate upward shift of the diastolic pressure-volume relation, particularly during exercise (exercise intolerance). The causes of diastolic failure are inappropriate tachycardia, decreased diastolic compliance and impaired systolic relaxation. Impaired (incomplete or slowed) systolic relaxation must be conceptually distinguished from compensatory prolonged systolic contraction (delayed or retarded relaxation). Optimal therapy will depend on the type of disease, the phase during the course of a given disease and the coexistence and relative contribution of various (de)compensatory processes. Treatment may consist of bradycardic, remodeling and lusitropic drugs. PMID- 8509557 TI - Serial changes during acute cardiac allograft rejection: quantitative ultrasound tissue analysis versus myocardial histologic findings. AB - OBJECTIVES: The aim of this study was to assess 1) whether quantitative ultrasound tissue analysis by serial measurements of myocardial echo amplitudes can detect and monitor the onset and degree of acute cardiac rejection, as well as its resolution of acute rejection during treatment, and 2) whether changes in myocardial echo amplitudes are modified by repeat additional rejection episodes. BACKGROUND: Previous experimental studies, all involving heterotopic heart transplantation, have consistently shown reproducible alterations in myocardial echo amplitude during acute rejection episodes untreated by immunosuppressive agents. METHODS: Two-dimensional echocardiographic long-axis views were obtained daily under strict standardization in 12 dogs after heterotopic cervical heart transplantation (mean survival time 16.1 days) and digitized into a 256 x 256 x 8 matrix. Myocardial echo amplitudes were analyzed by gray level histogram statistics in regions of interest (45 x 12 pixels) within the proximal septum and posterior wall and correlated with the results of daily transmural myocardial biopsies. Maintenance immunosuppressive therapy consisted of cyclosporine, azathioprine and steroids. Additive steroids were given during acute cardiac rejection. RESULTS: All dogs experienced at least one moderate or severe episode of acute cardiac rejection. Successful resolution and repeat acute rejection were observed in three dogs. On 65 days, the left ventricular biopsy specimens showed no evidence of acute rejection. Mild acute rejection was present on 36, moderate on 29 and severe rejection on 40 days. End-diastolic mean (+/- SD) gray level increased progressively from 100.7 +/- 20.4 for no acute cardiac rejection to 113.8 +/- 23.1 for mild rejection (p = NS vs. no rejection) to 126.0 +/- 16.1 for moderate rejection (p < 0.01) and to 136.3 +/- 12.6 for severe rejection (p < 0.01). In each individual dog, a correlation between daily measurements of mean gray levels and histologic cardiac rejection grades was found (rmean = 0.80 +/- 0.14 [range 0.57 to 0.97], n = 12). In three dogs with transient complete histologic resolution of acute cardiac rejection, mean gray level did not return to values before rejection (108.0 +/- 15.4 vs. 87.2 +/- 8.4). The subsequent second episode of rejection was characterized by higher gray level values than those associated with the first rejection episode (141.3 +/- 14.4 vs. 124.3 +/- 20.9). CONCLUSIONS: Acute cardiac rejection is associated with a progressive increase in mean gray level. Changes in myocardial echo amplitudes in individuals may thus prove a useful tool for the noninvasive detection and monitoring of acute rejection. Increased mean gray level values after resolution of rejection may indicate persistent structural tissue abnormalities after rejection and demonstrate the need to define new baseline values after histologic resolution of an acute rejection episode. PMID- 8509559 TI - Pulmonary embolism--diagnosis on a tombstone. PMID- 8509560 TI - Clinical competence in ambulatory electrocardiography. A statement for physicians from the ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology. PMID- 8509561 TI - Clinical competence in elective direct current (DC) cardioversion. A statement for physicians from the ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology. PMID- 8509562 TI - Estimating probability of coronary artery disease. PMID- 8509563 TI - 24th Bethesda conference: Cardiac transplantation. Task Force 6: Future developments. PMID- 8509564 TI - Cardiac transplantation. PMID- 8509565 TI - Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study. AB - OBJECTIVES: The aim of this study was to assess the efficacy of flosequinan in chronic heart failure. BACKGROUND: Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic benefits in heart failure, but large scale studies evaluating its clinical efficacy have not been reported. METHODS: One hundred ninety-three patients with chronic heart failure (New York Heart Association functional class II or III and left ventricular ejection fraction < 40%) receiving digoxin and diuretic drugs were randomly assigned (double-blind) to the addition of flosequinan (100 mg once daily, n = 93) or placebo (n = 100) for 3 months. The clinical status and exercise tolerance of each patient was evaluated at the start of the study and every 2 to 4 weeks during the trial while background therapy remained constant. RESULTS: After 12 weeks, maximal treadmill exercise time increased by 96 s in the flosequinan group but by only 47 s in the placebo group (p = 0.022 for the difference between groups). Maximal oxygen consumption increased by 1.7 ml/kg per min in the flosequinan group (n = 17) but by only 0.6 ml/kg per min in the placebo group (n = 23), p = 0.05 between the groups. Symptomatically, 55% of patients receiving flosequinan but only 36% of patients receiving placebo benefited from treatment (p = 0.018). In addition, fewer patients treated with flosequinan had sufficiently severe worsening of heart failure to require a change in medication or withdrawal from the study (p = 0.07). By intention to treat, seven patients in the flosequinan group and two patients in the placebo group died. CONCLUSIONS: These findings indicate that flosequinan is an effective drug for patients with chronic heart failure who remain symptomatic despite treatment with digoxin and diuretic drugs. The effect of the drug on survival remains to be determined. PMID- 8509566 TI - Hemodynamic effects of captopril and isosorbide mononitrate started early in acute myocardial infarction: a randomized placebo-controlled study. AB - OBJECTIVES: The aim of this study was to study the hemodynamic effects of orally administered captopril and isosorbide mononitrate in suspected acute myocardial infarction. BACKGROUND: Early treatment with converting enzyme inhibitors and nitrates in acute myocardial infarction may limit infarct expansion and prevent left ventricular dilation. METHODS: In a double-blind study, 81 patients were randomized within 36 h of the onset of symptoms of suspected acute myocardial infarction to 1 month of oral captopril (6.25 mg initial dose, followed 2 h later by 12.5 mg and continuing with 12.5 mg three times daily), isosorbide mononitrate (initial dose 20 mg followed by 20 mg three times daily) or matching placebo. The effects of treatment on changes from baseline in mean arterial blood pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed noninvasively using Doppler echocardiography 1 h after the first dose, 1 week after infarction and at 6 weeks (that is, 2 weeks after the scheduled end of trial treatment). RESULTS: One hour after the start of treatment, blood pressure was reduced by approximately 10% with both captopril and isosorbide mononitrate, but this difference did not persist at 1 week. Captopril was associated with a significant increase in cardiac output compared with placebo of 13 +/- 3% at 1 h (p < 0.01), 23 +/- 5% at 1 week (p < 0.001) and 22 +/- 6% (p < 0.05) at 6 weeks (2 weeks after the end of trial treatment). This increase in cardiac output with captopril was mainly due to a substantial and sustained increase in stroke volume, although there was also a small increase in heart rate at 1 week. Both captopril and isosorbide mononitrate reduced systemic vascular resistance within 1 h of the start of treatment, but only the effect of captopril was sustained (perhaps because the three-times daily nitrate regimen induced tolerance). Study treatment was well tolerated, and the incidence of withdrawal of study treatment for hypotension was not significantly different from that with placebo. CONCLUSIONS: This study indicates that the hemodynamic effects of both captopril and isosorbide mononitrate are well tolerated in the acute phase of myocardial infarction and that captopril favorably influences cardiac function. PMID- 8509567 TI - 24th Bethesda conference: Cardiac transplantation. Task Force 1: Organization of heart transplantation in the U.S. PMID- 8509568 TI - Association between atrioventricular node reentrant tachycardia and inducible atrial flutter. AB - OBJECTIVES: The purpose of this study was to evaluate the inducibility of atrial flutter in patients with atrioventricular (AV) node reentrant tachycardia and to determine the effect of radio-frequency ablation of the slow AV node pathway on the inducibility of atrial flutter. BACKGROUND: Studies have shown that both AV node reentrant tachycardia and atrial flutter are reentrant arrhythmias having an area of slow conduction that is located in the low posterior right atrium near the ostium of the coronary sinus. METHODS: Ninety-one patients were prospectively evaluated using a standardized atrial pacing protocol. Three groups of patients were analyzed: 42 patients with inducible AV node reentrant tachycardia, 13 with a history of spontaneous atrial flutter and 36 control patients. A subgroup of 34 patients with AV node reentrant tachycardia who underwent successful radiofrequency ablation of the slow AV node pathway underwent atrial pacing again after ablation. RESULTS: Atrial flutter was more frequently inducible in patients with AV node reentrant tachycardia (88%) and in those with a history of atrial flutter (92%) than in control patients (36%) (p = 0.0001). There were no differences between the patient groups with respect to atrial effective refractory period, P wave duration or PA interval at the His position. Among the 34 patients with AV node reentrant tachycardia who underwent atrial pacing before and after radiofrequency ablation, there were 30 with atrial flutter and 4 with atrial fibrillation before ablation and 29 with atrial flutter and 5 with atrial fibrillation after ablation (p = NS). There was no difference in the duration of the induced atrial flutter before and after ablation. The mean atrial flutter cycle length before ablation (206 +/- 22 ms) was not different from that after ablation (196 +/- 20 ms) (p = NS). CONCLUSIONS: There is a strong association between AV node reentrant tachycardia and inducible atrial flutter, suggesting that there may be a common area of perinodal atrium participating in the two tachycardia circuits. However, radiofrequency ablation of the slow pathway of the AV node reentrant tachycardia circuit does not influence the inducibility of atrial flutter. PMID- 8509569 TI - Long-term effectiveness of surgical treatment of ectopic atrial tachycardia. AB - OBJECTIVES: The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. BACKGROUND: Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. METHODS: The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. RESULTS: The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. CONCLUSIONS: Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs. PMID- 8509570 TI - Management of ectopic atrial tachycardia. PMID- 8509571 TI - Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults. AB - OBJECTIVES: The purpose of this study was to evaluate the efficacy of intravenous amiodarone in young patients. BACKGROUND: Oral amiodarone therapy has proved useful for problematic arrhythmias in children, but its pharmacokinetics with the oral route preclude its use in several acute settings. METHODS: Intravenous amiodarone was administered in 1-mg/kg body weight aliquots followed by continuous infusion to patients with potentially life-threatening tachyarrhythmias that had not been abolished by standard therapies. RESULTS: Ten patients (mean age 6.8 years) received intravenous amiodarone: for ventricular tachycardia in seven patients and for atrial tachycardia, junctional tachycardia and multiple arrhythmias in one patient each. Surgery for congenital heart defects had been performed previously in six patients. Two patients had a hamartoma causing ventricular tachycardia. Six of 10 patients had complete resolution of arrhythmia with intravenous amiodarone: 4 of 7 with ventricular tachycardia, 1 of 1 with atrial tachycardia and 1 of 1 with postoperative junctional ectopic tachycardia. Intravenous amiodarone was not successful in the two patients with a hamartoma but slowed ventricular tachycardia in one, allowing successful surgical cure. Average drug load at the time of effect was 4.8 mg/kg body weight. Four patients had transient hypotension during loading, corrected with volume or low dose calcium. Intravenous infusion of amiodarone, 10 mg/kg per day, continued an average of 3 days. Four of 10 patients died, all of nonarrhythmic causes not attributable to intravenous amiodarone. CONCLUSIONS: Intravenous amiodarone was well tolerated in this small series of patients. Postoperative ventricular tachycardia was responsive to intravenous amiodarone in 80% (8 of 10) of the patients (95% confidence interval 40% to 99%). Use of this drug in acute, postoperative tachyarrhythmias may be lifesaving in some patients when standard intravenous therapies fail. PMID- 8509572 TI - Direct and autonomically mediated effects of oral quinidine on RR/QT relation after an abrupt increase in heart rate. AB - OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/ 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine. PMID- 8509573 TI - Suggested approaches for research protocols involving the potential for life threatening reactions. AB - These guidelines are intended to reduce the potential for serious or life threatening reactions when clinical research is conducted. The following issues were addressed: identifying the risks involved in the research, providing adequate safeguards in the protocol design and during withholding of medication, anticipating risks, minimizing the chances for human error, providing resuscitative equipment sufficient to deal with the most serious anticipated life threatening reactions, planning for medical support in case of a life-threatening emergency, and optimizing the use of medical personnel and expertise to handle emergency situations. The guidelines also discuss important general issues about protocol design and implementation and the human subject consent form, which should facilitate the approval of protocols by the governing institutional review board. The guidelines are not meant to be inflexible or applicable to all research situations. However, it is our hope that they will allow for clinical research to be conducted in a manner that affords the research subjects a high degree of protection from unnecessary and possibly fatal injuries. PMID- 8509574 TI - Quality of life of subjects with occupational asthma. AB - BACKGROUND: The aim of the study was to assess the quality of life in subjects with occupational asthma after removal from exposure to the offending agent by comparison with a group of subjects paired for clinical and functional indices in order to show the separation between the two groups of subjects with a hypothesized different quality of life and relate the impairment in quality of life to anthropometric, clinical, and functional variables. METHODS: A previously described asthma quality of life questionnaire (Juniper EF, et al. Thorax 1992;47:76-83) was administered to two groups of subjects in a prospective manner. Information on the clinical and functional severity of asthma was obtained from each subject. Two groups of subjects were assessed: group 1, 134 subjects with occupational asthma who were seen more than 2 years after the diagnosis was confirmed, and group 2, 91 subjects who were seen in specialized asthma clinics of tertiary care hospitals for treatment of nonoccupational asthma and matched with 91 of the 134 subjects with occupational asthma from group 1 according to need for medication and (when available), baseline forced expiratory volume in 1 second (FEV1), and level of bronchial responsiveness. RESULTS: A statistically significant difference was seen in the four domains (asthma symptoms, limitation of activities, emotional dysfunction, environmental stimuli) and in the total score of the quality of life questionnaire between the two groups of matched subjects; the mean difference in the total score was 0.6 on a scale of 1 (no limitation or none of the time) to 7 (severe limitation or all the time). A weak but statistically significant correlation between the total score and several indices (FEV1, bronchial responsiveness and asthma severity) was generally obtained. CONCLUSION: The quality of life of subjects with occupational asthma is slightly less satisfactory than that of subjects paired for clinical and functional indices, although the magnitude of the difference is small; and quality of life is weakly correlated with clinical and functional indices. PMID- 8509575 TI - Immunoglobulin E reactivity to latex antigens in the sera of patients from Finland and the United States. AB - BACKGROUND: Patients with latex sensitivity and latex antigens from the United States and Finland, two countries where allergic reactions to latex have been widely reported, were evaluated to determine the spectrum of immune responses. METHODS: Sera from 27 patients from Finland and 18 from the United States with latex allergy and control sera from nonsensitive individuals were studied for latex-specific IgE antibodies. Four antigen preparations were used: two extracted from gloves and one each extracted from rubber tree sap from Malaysia and India. All 45 patients had skin prick test results that were positive to latex antigens, and all sera were evaluated by enzyme-linked immunosorbent assay (ELISA) with the various antigens. RESULTS: There were considerable differences in the reactivity of patient sera with the different antigens. Only 50% of the sera from patients with latex allergy from Finland demonstrated significant levels of IgE to latex as determined by enzyme-linked immunosorbent assay. These patients showed more reactivity with rubber tree sap antigens than with glove antigens. However, 72% of the patients from the United States demonstrated antibodies to latex, and no marked differences were noted between the antigen extracts. CONCLUSIONS: The results indicate that reagents such as rubber tree sap, which contain multiple clinically significant antigenic components, should be included in evaluation of latex allergy and that differences in patient populations may result in serologic variances. PMID- 8509576 TI - Breast milk from mothers of children with newly developed atopic eczema has low levels of long chain polyunsaturated fatty acids. AB - BACKGROUND: Infants at risk of atopic dermatitis have lower than normal levels of long chain polyunsaturated fatty acids. These fatty acids are normally present in substantial quantities in human breast milk. METHODS: Because of the equivocal evidence concerning the ability of breastfeeding to delay the onset or reduce the severity of atopic dermatitis, we have analyzed the fatty acid composition of breast milk from the mothers of children with newly developed disease with the use of gas chromatography. RESULTS: Breast milk lipids from mothers of children with newly developed atopic dermatitis had increased proportions of linoleic acid and significantly decreased proportions of its long chain polyunsaturated derivatives compared with a control group. The ratio of linoleic acid to the sum of its metabolites, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid was 11.78 in the atopic group and 9.02 in the control group (p < 0.01). CONCLUSIONS: These results are consistent with previous findings of an abnormal fatty acid status in atopic subjects and may account for some of the inconsistent results from studies of the effect of breastfeeding on the subsequent development of atopic dermatitis. We conclude that further studies to examine the effects of supplementation of the diet of breastfeeding mothers with long chain polyunsaturates should be done. PMID- 8509577 TI - Skin and serologic testing in the diagnosis of latex allergy. AB - BACKGROUND: Latex hypersensitivity is associated with occupational allergy, contact urticaria, rhinitis, asthma, and anaphylaxis. However, standardized sensitive and specific latex extract for skin prick or serologic testing is not available in the United States. METHODS: We investigated the reliability of two latex extracts in 118 consecutive skin tests in patients with spina bifida, health care workers, and other patients with symptoms of latex allergy, and 10 control subjects. RESULTS: Forty-two of 86 patients with spina bifida, 11 of 15 health care workers with symptoms of latex allergy, 6 of 7 patients with symptoms of latex allergy, and 0 of 10 control subjects had demonstrable immediate wheal and flare responses to latex prick testing. In addition, 95 patients and 10 control subjects were tested concurrently for latex-specific IgE by ELISA. Of 55 patients with positive skin prick test results, 48 were reactive as determined by ELISA for IgE-specific latex antibody (sensitivity = 87%). Latex ELISA titers were significantly higher in patients with positive skin prick test results with a history of anaphylaxis to latex and in individuals without symptoms of latex allergy who had positive skin prick test results when compared with patients with negative skin prick test results. During the skin test procedure, nine patients had adverse reactions, including anaphylactic reactions in four. CONCLUSIONS: Skin prick and serum testing are reliable methods of diagnosing latex allergy. Serologic evaluation may be more desirable until allergen standardization is available. PMID- 8509578 TI - Once daily fluticasone propionate is as effective for perennial allergic rhinitis as twice daily beclomethasone diproprionate. AB - BACKGROUND: Fluticasone propionate aqueous nasal spray, a new potent corticosteroid, is effective when given once or twice daily for seasonal allergic rhinitis. METHODS: Fluticasone propionate was compared with beclomethasone dipropionate in a multicenter double-blind, randomized, placebo-controlled, parallel-group study in 466 patients with perennial allergic rhinitis. Adults and adolescents (aged 12 to 71 years) with moderate to severe symptoms, nasal eosinophilia, and a positive skin test reaction (> or = 2+) to a perennial allergen received fluticasone propionate aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice daily, or placebo for 6 months. RESULTS: Clinician- and patient-rated scores for nasal obstruction (including obstruction on awakening), rhinorrhea, sneezing, and nasal itching were reduced by the first visit at 7 days after initiation of active treatment and remained lower than those of patients receiving placebo throughout the 6-month treatment period. Nasal eosinophilia was reduced in significantly more patients receiving active treatment. The incidence of adverse events was similar in all four treatment groups except for blood in nasal mucus, which was reported by significantly more patients in the two twice-daily active treatment groups compared with the placebo group. There was no evidence of systemic effects of fluticasone propionate. There were no significant differences between fluticasone propionate given once or twice daily or beclomethasone dipropionate given twice daily for any efficacy or safety evaluation. CONCLUSIONS: Fluticasone propionate aqueous nasal spray given once daily in the morning is safe and effective therapy for perennial allergic rhinitis and is as effective as twice daily dosing with fluticasone propionate or beclomethasone dipropionate. PMID- 8509579 TI - Beclomethasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not. AB - BACKGROUND: Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn. METHODS: In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20. RESULTS: The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18). CONCLUSION: Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested. PMID- 8509580 TI - Upregulation of formyl-peptide and interleukin-8-induced eosinophil chemotaxis in patients with allergic asthma. AB - BACKGROUND: The cytokine granulocyte-macrophage colony-stimulating factors, interleukin-3 and interleukin-5, are important modulators of eosinophilia and eosinophil function. In particular, eosinophil chemotaxis is very sensitive to cytokine priming. METHODS: We evaluated chemotactic responses of eosinophils from patients with allergic asthma. These cells exhibited a primed phenotype as deduced from enhanced responses toward formyl-methionyl-leucyl-phenylalanine and platelet-activating factor and a decreased responsiveness toward granulocyte macrophage colony-stimulating factor. Bronchoprovocation of patients with allergic asthma with allergen was performed as a possible means to enhance in vivo priming. RESULTS: Indeed, eosinophils isolated 3 hours after allergen challenge exhibited a more pronounced primed phenotype, which was reflected by an induction of responsiveness towards interleukin-8. Eosinophil responses induced by platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, complement fragment C5a, interleukin-3, interleukin-5, and granulocyte-macrophage colony stimulating factor were not significantly altered after allergen challenge. CONCLUSION: These data provide further evidence that eosinophils are already primed in the peripheral blood of individuals with allergic asthma. This is most likely due to the presence of circulating cytokines in the peripheral blood of those individuals. This in vivo priming results in selective upregulation and downregulation of responses toward various chemotaxins, which may be released in the lungs during allergic inflammation. PMID- 8509581 TI - Pokeweed mitogen induces IgE synthesis in the presence of a blocking antibody to the interferon-gamma receptor. AB - BACKGROUND: Although pokeweed mitogen (PWEM) can induce peripheral blood mononuclear cells (PBMCs) to synthesize IgG, IgA, and IgM, such cultures fail to induce IgE synthesis. The present study examined the possibility that the stimulation of interferon-gamma (IFN-gamma) production plays a role in the failure of PWM to induce IgE synthesis. METHODS: We examined PBMCs from eight normal control subjects for IFN-gamma and IL-4 production. Since IFN-gamma synthesis is known to inhibit IgE synthesis, we also examined the effect of a neutralizing anti-IFN-gamma antibody and of two anti-IFN-gamma receptor antibodies, monoclonal antibody (mAb) GIR208, which blocks cellular binding of IFN-gamma, and mAB GIR94.5, which binds to the IFN-gamma receptor but does not block the binding of IFN-gamma to its receptor on PWM-stimulated PBMCs. RESULTS: After stimulation with PWM, culture supernatants contained significantly more IFN gamma (p = 0.001) and IL-4 (P = 0.001) compared with supernatants from nonstimulated cultures. PWM-stimulated PBMCs also expressed higher levels of IFN gamma and IL-4 gene transcripts than unstimulated cells. When cultured in the presence of anti-IFN-gamma, supernatants from PWM-stimulated cultures also induced CD23 on Ramos B cells in an IL-4-dependent manner. In the presence of mAB GIR208 and a neutralizing anti-IFN-gamma antibody, but not mAb GIR94.5, PWM stimulated PBMCs from eight normal control subjects and six patients with atopic dermatitis to produce IgE. Monoclonal antibody GIR208, however, did not enhance IgG synthesis. Furthermore, the exogenous addition of IFN-gamma inhibited the IgE stimulatory effect of mAb GIR208. Monoclonal antibody GIR208 was unable to induce purified B cells to synthesize IgE in the presence of IL-4. CONCLUSIONS: Thus unlike anti-CD40, mAb GIR208 does not act as a second signal for the induction of IgE synthesis. These results demonstrate that the induction of IFN-gamma production contributes to the failure of PWM to stimulate synthesis of IgE in PBMCs from atopic and nonatopic donors. PMID- 8509582 TI - Food intake in combination with a rise in body temperature: a newly identified cause of angioedema. PMID- 8509583 TI - Local intravaginal desensitization to seminal fluid. PMID- 8509584 TI - Anaphylaxis to coriander: a sleuthing story. PMID- 8509585 TI - Meeting the challenge of the renal diet. A preview of the "National Renal Diet" educational series. PMID- 8509586 TI - Finn urges Congress to include nutrition services in the standard health benefits package. PMID- 8509587 TI - Challenges facing public health policy. PMID- 8509588 TI - Effect on serum lipids of addition of safflower oil or olive oil to very-low-fat diets rich in lean beef. AB - The cholesterol-lowering effect of very-low-fat diets rich in lean beef has previously been shown to be reversed with the addition of beef fat. The aim of this study was to determine the effect on serum lipid levels of the addition of safflower oil or olive oil to a very-low-fat diet rich in lean beef. Subjects were assigned to either the safflower oil or the olive oil group. In the first week the subjects ate their usual diet; in the second and third weeks all subjects ate a very-low-fat (9% of energy) diet rich in lean beef. In the fourth and fifth weeks the fat content of the diet was increased in a stepwise fashion to 20% and 30% of energy, respectively, by substituting safflower oil or olive oil for carbohydrate. Low-density lipoprotein cholesterol (LDL-C) concentrations decreased by 13% to 14%, and high-density lipoprotein cholesterol (HDL-C) concentrations decreased by 20% to 25% in subjects after 2 weeks of the very-low fat, lean-beef diet. The LDL-C concentrations remained low after the addition of safflower oil or olive oil to the very-low-fat diet. These results indicate that a reduction in saturated fat, not total fat, is required to reduce serum total cholesterol and LDL-C levels. Provided that the total diet is low in saturated fat, these serum lipid responses can be achieved even when the diet is rich in fat-trimmed lean beef. PMID- 8509589 TI - Reconstruction of past calcium intake patterns during adulthood. AB - This study illustrates a cognitive recall method based on time lines and retrieval cues to reconstruct the patterns of use of selected dairy products as important calcium sources. We administered a semiquantitative retrospective instrument that assessed past intakes of milk, milk-based chocolate beverages, and cheese to 35 healthy women aged 50 to 65 years. The recall time line for each subject began at the age of 20 and continued forward to the interview. Thirty-one women reported a change in calcium intake from the baseline level at age 20. Seventeen had changed their intake by more than 50%. Milk was the food item the most subject to change. The magnitude of change along the time line was quite important as intraindividual intakes differed by 100 to 300 mg of calcium per day in 11 women and differed by more than 300 mg of calcium per day in 12 others. After age 50 there was an upward trend in calcium use, which coincides with higher calcium requirements after menopause. Health concerns and food preferences were the prominent motives that triggered changes. The findings suggest that the cognitive recall method could provide necessary information on lifelong food patterns implicated in chronic disease development. PMID- 8509590 TI - Exercise training and nutrient intake in elderly women. AB - This study examined the relationship between moderate exercise training (five 30- to 40-minute sessions per week for 12 weeks at 60% of heart rate reserve) and changes in nutrient intake in a group of 30 sedentary elderly women aged 67 to 85 years. Subjects were placed randomly into two groups (those who walked and those who did calisthenics) and were followed for 12 weeks. Measurements were done at three times (baseline, 5 weeks, and 12 weeks). Dietary intake was based on 7-day food records. The 12-week walking program resulted in a significant (12.6%) improvement in maximum oxygen consumption (VO2max) but no change in body weight or skinfold thicknesses compared with the calisthenics program. Despite the improvement in cardiorespiratory fitness, no significant group x time interaction effects were observed for most of the nutrient intake variables tested. To test the effects of high levels of physical activity on nutrient intake, cross sectional comparisons were made at baseline between highly conditioned and sedentary elderly women. The highly conditioned elderly women had higher energy and nutrient intakes, especially when expressed on a weight-adjusted basis. However, no differences in measures of dietary quality were found. Dietitians should not expect spontaneous improvement in either the quantity or quality of nutrient intake by elderly women who adopt a moderate exercise program. Although nutrient intake was greater in highly conditioned elderly women, their level of fitness and physical activity may be beyond the reach of many elderly women. PMID- 8509591 TI - Parenteral nutrition: hospital to home. AB - Parenteral nutrition support is the provision of essential nutrients intravenously, bypassing the intestinal tract. It is used in a variety of clinical settings and medical conditions. Parenteral nutrition is a complex technology that requires the input of many professionals, including dietitians. The role of the dietitian in parenteral nutrition support involves direct patient care, consultative services, education, program development, and research. Even though this field of practice is still developing, some common practices can be described. Nutrition assessment determination of macronutrient and micronutrient requirements, and monitoring are vital aspects of the provision of parenteral nutrition support that benefit from the knowledge and experience of a dietitian. The future of parenteral nutrition includes identification of preferred fuels for specific disease states, development of new lipid emulsions, and identification of conditionally essential nutrients. PMID- 8509592 TI - Role of magnesium in regulation of lung function. AB - Magnesium and calcium play multiple dynamic roles in pulmonary structure and function. When magnesium is deficient, the action of calcium is enhanced. In contrast, an excess of magnesium blocks calcium. These interactions are important to the respiratory patient because the intracellular influx of calcium causes bronchial smooth-muscle contraction. The possibility exists that magnesium deficiency contributes to pulmonary complications. During the past few years, there has been an increase in calcium consumption in the US population but little change in magnesium intake, which has caused an imbalance in the calcium:magnesium ratio. Although serum levels are used to assess magnesium deficiency, cells can be deficient despite normal serum values. These findings indicate that pulmonary patients should be monitored routinely for magnesium deficiency. PMID- 8509594 TI - Weight loss contests at the worksite: results of repeat participation. PMID- 8509593 TI - Using quality assurance procedures to improve compliance with standards of nutrition care for patients receiving isotonic tube feeding. PMID- 8509595 TI - Customizing mainframe computer software to improve the productivity of clinical dietetics. PMID- 8509596 TI - Professional image of British and American dietitians. PMID- 8509597 TI - Health care reform legislative platform: economic benefits of nutrition services. PMID- 8509598 TI - Position of the American Dietetic Association and the Canadian Dietetic Association: nutrition for physical fitness and athletic performance for adults. AB - The importance of diet and healthful food choices in optimizing health status, fitness levels, and athletic performance has been recognized by both participants and professionals. There continues to be a need for the interpretation of new research findings in this fast-growing discipline and for the dissemination of nutrition information and training techniques for a broad spectrum of individuals involved in various forms of physical activity. The registered dietitian who has specialized in exercise physiology and sports nutrition has the knowledge and counseling skills to act as the provider of this nutrition information. Additional information may be obtained in the Sports Nutrition Manual, 2nd edition, published by The American Dietetic Association and the Sports and Cardiovascular Nutrition dietetic practice group as well as in Sport Nutrition for the Athletes of Canada, published by the Sport Nutrition Advisory Committee of the Sports Medicine and Science Council of Canada. PMID- 8509599 TI - Synthesis of RNA probes by the direct in vitro transcription of PCR-generated DNA templates. AB - We describe a novel method for the generation of RNA probes based on the direct in vitro transcription of DNA templates amplified by polymerase chain reaction (PCR) using primers with sequence hybrids between the target gene and those of the T7 and T3 RNA polymerases promoters. This method circumvents the need for cloning and allows rapid generation of strand-specific RNA molecules that can be used for the identification of genes in hybridization experiments. We have successfully applied this method to the identification of DNA sequences by Southern blot analysis and library screening. PMID- 8509600 TI - Comparison of Ellman's reagent with N-(1-pyrenyl)maleimide for the determination of free sulfhydryl groups in reduced cellobiohydrolase I from Trichoderma reesei. AB - The enzyme cellobiohydrolase I (CBH I) from Trichoderma reesei was treated with 5 mM dithiothreitol at different pH values in order to reduce some or all of its 12 disulfide bridges. A discrepancy was found in the number of free sulfhydryl (SH) groups generated upon the reduction of CBH I when they were measured using N-(1 pyrenyl)maleimide (PM) or Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid). For example, the number of SH mol generated/mol CBH I at pH 8.5 was determined to be 16 and < 1 when measured using PM or Ellman's reagent, respectively. The low value obtained with Ellman's reagent may be due to the electrostatic repulsion between the carboxylic acid groups in CBH I and those in Ellman's reagent. The fluorimetric assay used for determining SH molecules in reduced CBH I, based on their reaction with PM, is described. PMID- 8509601 TI - A new kinetic single-stage Limulus amoebocyte lysate method for the detection of endotoxin in water and plasma. AB - A convenient kinetic chromogenic Limulus amoebocyte lysate (LAL) method, based on components originally intended for a two-stage end-point method, has been developed. The components (LAL and chromogenic substrate) can be pooled and subsequently used in a single-stage kinetic procedure adapted to microplates. With the help of a kinetic software, it is possible to measure over the three log range 0.005-12 EU/ml in one test run--a range considerably wider than the range of the end-point procedure. A good linearity of the log-log standard curve, reflected by coefficients of regression between 0.997 and 1.0, is shown as well as a high-resolution (> 700 s) between the negative control and the lowest standard point. Moreover a good precision (C.V. < 10%) is obtained in both water and plasma, showing the usefulness of the method in different applications. Finally, a strong correlation (r = 0.95-0.99) to other LAL methods is demonstrated. PMID- 8509602 TI - A simple technique for the immobilization of lysozyme by cross-linking of hen egg white foam. AB - A novel technique has been described for the immobilization of lysozyme, naturally present in hen egg white by cross-linking the egg white foam with glutaraldehyde. This technique results in a mechanically stable and porous matrix exhibiting about 6-times the lytic activity against Micrococcus lysodeikticus cells, as compared to the unfoamed matrix. Foamed egg white matrix can be used for the continuous lysis of bacterial cells. PMID- 8509603 TI - A differential heat-conduction microcalorimeter for heat-capacity measurements of fluids. AB - A heat-conduction calorimeter has been developed for measuring small changes in heat capacity of milligram samples of membrane lipid dispersed in water as a function of temperature. The operation of the instrument is based on the principle that the thermal response of the sample to a short (10 s), electrically generated heat burst is a function of the diffusivity of the sample. Modeling studies of the instrument's performance have revealed that the output response after the heat burst is a function of only the heat capacity, rho Cp. Calibration of the instrument experimentally confirmed this behavior. This feature obviated the need to measure the thermal conductivity in order to determine rho Cp from the diffusivity equation, eta = lambda/rho Cp. The calorimeter has the following characteristics: reproducibility of loading: +/- 400 microJ/C degrees.cm3; baseline stability: +/- 10 microJ/C degrees.cm3 per 36 h; resolution (+/- 1 S.D.): +/- 50 microJ/C degrees.cm3; sample size 600 microliters. PMID- 8509604 TI - Bradford protein assay and the transition from an insoluble to a soluble dye complex: effects of sodium dodecyl sulphate and other additives. AB - The addition of sodium dodecyl sulphate (SDS) (0.0015-0.006%), phenol (0.25-0.5%) or sodium hydroxide (0.025-0.1 M) to the Bradford dye reagent does not improve the solubility of the Coomassie blue-protein dye complex. Centrifugation of the assay tubes, 10 min after the addition of reagent, results in complete loss of colour yield as indicated by the absorbance (A595) of the recovered supernates. At protein-concentrations above the working range of the assay, centrifugation indicates a transition from an insoluble to a soluble protein-dye complex. This transition is characteristic of an individual protein and is influenced by assay modification. Low protein concentrations appear to provide nucleation sites for precipitation of Coomassie blue whilst higher protein concentrations increase its solvation. A soluble dye chromophore is only formed above the working range of the assay indicating that precipitation of the dye by protein contributes to the assay mechanism. PMID- 8509605 TI - Elder care. A diagnostic model for failure to thrive. AB - 1. Care of the elderly is often complicated by complex, interacting conditions. Major areas of concern for the elderly are malnutrition, depression, and confusion (in the form of dementia or delirium). Malnutrition has been prevalent in both hospitalized and institutionalized elderly. 2. Failure to thrive (FTT) has long been recognized in pediatric patients as a multifaceted syndrome that is primarily a disorder of nutritional status and physical and mental development. The characteristics of FTT in the elderly are undernutrition, loss of physical and cognitive function, and depression. 3. The redefinition and alteration of terms from the infant model of FTT results in three categories of FTT in the elderly--psychosocial, predisposing, and physical, as opposed to the two categories of FTT in infants--the infant and the environment. PMID- 8509606 TI - Tube feeding: complications among the elderly. AB - 1. The elderly who are receiving nutritional support through nasogastric feeding are at higher risk for complications. Most common complications include aspiration, clogging, agitation, and diarrhea. 2. Agitation, which can lead to self-extubation among the elderly receiving tube feeding, is seen as undesirable and elderly patients end up being restrained. The use of restraints, whether chemical or physical, can lead to further complications. Immobilization by restraint has no place in the nutritional support of the elderly. 3. Nurses play an important role in providing safe nutritional support. Only through research can weaknesses and strengths of nursing practice be identified, and be able to provide an alternative, modification, or support to the present practice. PMID- 8509607 TI - Wound care: fact and fiction about hydrocolloid dressings. AB - 1. Hydrocolloid dressings have two layers. The inner, hydrocolloid adhesive layer has particles that absorb exudate to form a hydrated gel over the wound, creating a moist environment that promotes healing and protects new tissue. The outer layer (film, foam, or both) forms a seal to protect the wound from bacterial contamination, foreign debris, urine, and feces; it also maintains a moist environment and helps prevent shearing. 2. Hydrocolloid dressings are designed to be worn for up to a week. Infrequent dressing changes are less disruptive to the wound bed, provided that healthy skin is not compromised. Many patients--and even some medical professionals--still incorrectly believe that wounds need to be exposed to the air to heal properly. 3. Hydrocolloids are not always the dressing of choice in wounds that have limited drainage or in wounds with copious amounts of drainage. The hydrocolloid dressing is designed to manage drainage; if drainage is minimal, another approach may be more economical and comfortable for the patient. PMID- 8509608 TI - Research considerations: nursing home quality perceptions. AB - 1. One of our nation's most challenging health care problems is providing quality care for nursing home residents. Those of us who desire to evaluate and to improve the quality of care provided in a nursing home must attempt to define quality in specific terms, even though it is a product of many factors. 2. Ideally, there should be congruence between resident and staff perceptions of the importance and occurrence of indicators of quality in a nursing home setting. However, minimal to moderate congruence of perceptions was found in this study. 3. The fact that the majority of 30 residents in two nursing homes considered these 17 quality indicators to be important further validates them as markers of the quality of care in nursing homes. Use of a comprehensive quality assurance process that includes some or all of these indicators for evaluating and improving care in nursing homes could demonstrate a real commitment to quality that would go beyond only responding to the requirements of consumers and external regulators. PMID- 8509609 TI - Baccalaureate curriculum. Gerontological nursing objectives. AB - 1. Gerontological preparation for nursing practice is no longer a curricular luxury; it is a necessity. Baccalaureate nursing education must include broad content and guided practice in gerontological nursing. 2. Incorporating gerontology into a baccalaureate nursing curriculum often is a challenge. Reasons include gerontology not being a "traditional" specialty area; health care professionals in the United States, including nurses, not viewing older adults differently from younger adults; students not being expected to apply knowledge or concepts specifically related to gerontology; and efforts to incorporate gerontological content into a curriculum being resisted due to ageism--a "natural" avoidance of aging from which nursing faculty are not exempt. 3. Because of the limited numbers of nurses with an advanced education in gerontology, the recruitment of experienced, knowledgeable faculty is difficult. Most gerontology faculty are still largely self-taught and enter nursing education via the fields of medical/surgical, psychiatric, or community nursing. It is largely these faculty who must plan and "pioneer" gerontology in the curriculum. PMID- 8509610 TI - Screaming in silence. PMID- 8509611 TI - Informal caregivers: reframing nursing goals and strategies. PMID- 8509612 TI - Reality orientation and validation therapy. Dementia, depression, and functional status. AB - 1. This study shows that Reality Orientation (RO) and Validation Therapy have no significant impact on mental status, level of depression, or functional status. 2. Gerontological nurses, administrators, specialists, and practitioners must carefully evaluate and compare all relevant research studies on therapies before implementing therapies in long-term care settings. 3. Gerontological nurse researchers and staff must be aware of the difficulties arising in long-term research: sampling difficulties, patients' behavioral and physical factors, and environmental, staff, and financial resources. PMID- 8509613 TI - Cryptocotyle lingua in mullet, Chelon labrosus; significance of metacercarial excretory proteins in the stimulation of the immune response. AB - 'O' group mullet, Chelon labrosus, were experimentally infected with Cryptocotyle lingua (Heterophyidae) by tail dip in a suspension of cercariae. Metacercariae were excised after 1 and 24 hours and prepared for TEM and post-embedding immunogold labelling. Antisera to cercariae of C. lingua were raised in adult mullet by natural infection via the skin and by intra-peritoneal injection of sonicate. The membrane-bound vesicles within the syncytial lining of the metacercarial excretory vesicle were found to be intensely antigenic with both antisera; the epidermal secretory bodies type 5 within the cystogenous glands gave a positive response. Penetration gland contents were not found to be antigenic with either antiserum. Discharge of the membrane-bound vesicles coinciding with both the reorganization of the lining of the metacercarial excretory vesicle and with cyst wall formation appears to be of significance in the initiation of the host immune response. That the term 'excretory vesicle' in Digenea may be a misnomer is discussed in the light of current information regarding the wide range of functions attributed to this structure. PMID- 8509614 TI - The effect of infection with Schistosoma margrebowiei on the growth of Bulinus natalensis. AB - Three age groups of Bulinus natalensis, immature, mature but not yet egg-laying and mature egg-laying, were infected with miracidia of Schistosoma margrebowiei. The growth of infected, exposed but showing no signs of infection, and uninfected control groups, were examined at weekly intervals for ten weeks post exposure. Snails exposed to infection when immature, even in the group where no patent development ensued, showed a statistically significant reduction in growth and this was evident as early as 2-5 weeks post exposure. When infection occurred at the stage prior to egg-laying a significant reduction in growth was seen but only in the group which developed a patent infection. This was also the case for the egg-laying group although the reduction in growth was only significant in the final three weeks of the experiment. Thus in all three age groups, growth rate was reduced and the infected snails were significantly smaller at the end of ten weeks compared with the controls. The reasons for these effects are discussed. PMID- 8509615 TI - A morphological study of the effects of liposomized albendazole on the muscle phase of Trichinella spiralis in mice. AB - The pathomorphological effects of daily and weekly doses of liposomized albendazole on Trichinella spiralis larvae have been examined and compared during the course of muscle infections in mice. Treatment with three and six daily doses of the drug given by intraperitoneal injection to mice resulted in marked pathological alterations to encapsulated larvae, mainly in the walls of the capsules. There was a 5% efficacy against T. spiralis in mice given three daily doses of albendazole, and 38% efficacy in mice given six daily doses of the drug. The same doses of drug, when administered weekly, did not reduce the numbers of parasite larvae, and the application of drug at 6-weekly intervals resulted in a 5% reduction in numbers. PMID- 8509616 TI - Biological control of Ostertagia ostertagi by feeding selected nematode-trapping fungi to calves. AB - Three nematode-trapping fungi, one Arthrobotrys oligospora and two Duddingtonia flagrans isolates, were fed to Ostertagia ostertagi-infected calves to test their ability to destroy larvae of this parasite in faeces and consequently to reduce the transmission of infective larvae to herbage. The fungi had previously been selected for their capability to pass the alimentary tract of cattle without losing growth and nematode-trapping potentials. Dung was collected from three calves each fed one of the three fungi and placed as 1-kg cow pats on a parasite free grass plot together with control cow pats from a calf that was not given fungi. The cow pats contained comparable concentrations of parasite eggs. The two D. flagrans isolates were highly effective in that they reduced herbage larval infectivity by 74-85%. In contrast, A. oligospora did not show any effect in the present experiment. Field experiments will demonstrate if D. flagrans represents a potential organism for biological control of bovine gastrointestinal nematodes under practical agricultural management conditions. PMID- 8509617 TI - The antibody response to Dracunculus medinensis in an endemic human population of northern Ghana. AB - The serum antibody response (total, and isotypes IgG1, IgG4, IgM, IgA and IgE) to Guinea worm infection was examined in humans from a highly endemic area of northern Ghana by ELISA and SDS-PAGE/Western blot techniques using an adult D. medinensis antigen. Sera were obtained early and late in the peak transmission period, from persons with patent and postpatent infections, as well as from persons from the same endemic area who claimed never to have had Guinea worm infection. To observe for potential cross-reactions in the tests, sera were also obtained from areas with no transmission of Guinea worm from patients with hookworm, O. volvulus and W. bancrofti infections, and from non-infected controls. Sera from persons living in the Guinea worm endemic area reacted extensively with Guinea worm antigen in both tests, and large numbers of bands were produced in the Western blots (up to 35 identified for some sera). For most antibody isotypes, the ELISA absorbance values obtained with sera from the same individuals varied between the two transmission seasons, with the highest titres present towards the end of the peak transmission period. The mean antibody titres for persons in the patent and postpatent infection categories were not significantly different when sera were obtained at the same season of the year. Persons from the endemic area, who claimed never to experience patent infections, also had antibodies to Guinea worm, although at significantly lower mean levels than for the patent and postpatent categories. The highest specificity in the ELISA and the most homogenous Western blots were obtained when detecting for antibodies of the IgG4 isotype. PMID- 8509618 TI - Observations on the morphology of adults and larval stages of Oesophagostomum sp. isolated from man in northern Togo and Ghana. AB - Infection with Oesophagostomum sp. appears to be extremely common in man in northern Togo and Ghana. Adult specimens were recovered from the intestinal lumen by treatment with pyrantel pamoate and the morphological characteristics of oesophagostomes of man could for the first time be compared with information available on the morphology of oesophagostomes of monkeys. The observations and measurements demonstrated that the species involved is Oesophagostomum bifurcum and that the eggs of this species cannot be differentiated from those of Necator americanus. Both infections occur simultaneously in the population involved. The L1 larvae, too, cannot be differentiated from hookworm L1 larvae. The L3 larvae, however, are characteristic. Diagnoses of human Oesophagostomum infections is based on the detection of these larvae in coprocultures. In the present paper, the eggs, the L1 and L3 larval stages and the adults, are carefully described and photos are given. PMID- 8509619 TI - Studies on cryopreservation of third-stage larvae of Parastrongylus cantonensis. AB - Attempts have been made to increase the survival rate of third-stage larvae of Parastrongylus cantonensis during cryopreservation. Parasites were obtained from experimentally infected snails, Biomphalaria glabrata. The maximum non-toxic concentrations of cryoprotectants dimethyl sulphoxide (DMSO) and glycerol were determined as 10% v/v in NCTC 109 medium. Different pre-cooling times and serum additives were assayed to determine their effects on the viability of larvae. Larvae pre-cooled at -20 degrees C for 15-20 minutes before transfer to -70 degrees C had the optimum survival rate. The presence of serum was essential for further cooling to -196 degrees C. There were no differences between native and heat-inactivated sera on the larval viability. The survival of larvae recovered after storage at -196 degrees C was higher in sera collected from the rat, man, or fetal calf than in sera collected from the mouse, dog, or horse. Viability assessed by mouse-infections showed that thawed larvae retained infectivity for susceptible hosts, but it was significantly lower than that of unfrozen control worms. PMID- 8509620 TI - On an infection of a human eye with Parastrongylus (= Angiostrongylus) sp. in Sri Lanka. AB - A metastrongyle worm extracted from the anterior chamber of the right eye of a patient in Sri Lanka belongs to the genus Parastrongylus and probably to a yet undescribed species, related to P. cantonensis well known to infect man. It is mostly a parasite of rodents, wandering in man and unadapted to this host. Evidence for this lack of adaptation are that the specimen is undergoing necrosis (teratological specimen) and is located in an organ with little immunological defences. PMID- 8509621 TI - Epidemiology of Toxocara vitulorum in cattle around Bursa, Turkey. AB - The prevalence of Toxocara vitulorum in cattle around Bursa, Turkey, was surveyed by faecal examination of eggs. The average infection rate among 11 towns was 5.1% in calves younger than 6-months-old, and 2.2% in all ages of animals. T. vitulorum was found to be prevalent in two different areas of Bursa. Third stage larvae were found in one milk sample and therefore galactogenic transmission was suggested. Experimental incubation of eggs showed that the optimum temperature for development was 20 to 30 degrees C and eggs could survive under low temperature, indicating that grazing in the contaminated pasture may accelerate the transmission of eggs to cows. Mode of farming, therefore, affects the infection rate of T. vitulorum and may explain the difference in the rate between the two areas. PMID- 8509622 TI - Prevalence of Toxocara eggs and number of faecal deposits from dogs and cats in sandpits of public parks in Japan. AB - Contamination of 13 sandpits in public parks in Hyogo Prefecture, Japan, by Toxocara eggs and animal faeces was studied. All 13 sandpits were contaminated with faeces. The mean number of faeces found in 1 m2 of the sandpits was 35, from which the number of faeces in each sandpit was estimated to be 261 to 2205. Toxocara eggs were detected in 12 of the 13 sandpits, each examined 4-15 times; the overall prevalence was 92%. The eggs were not always distributed in the same pattern, but in general, eggs were numerous on the sandpit surface but also present at depths of about 35 cm. Of the eggs recovered, 63% were fully embryonated. Of the 13 sandpits examined, two were heavily contaminated by eggs, and all but one of the others were mildly contaminated. The difference between heavy and light contamination was not related to differences in the environment or in the number of faeces; the cause is unknown. PMID- 8509623 TI - A probable case of vertical transmission of Onchocerca volvulus microfilariae. AB - A probable case of vertical transmission of Onchocerca volvulus microfilariae in Dass Bauchi State, Nigeria is presented. A 28-week-old male child delivered by a 39-year-old Fulani woman suffering from onchocerciasis was positive for O. volvulus microfilariae based on skin snip examinations. The child had general body pruritic rash and intermittent fever. Although the child's skin snip on re examination five weeks later was also positive, the fever had gradually subsided. PMID- 8509624 TI - Comparative study of two methods for the diagnosis of Enterobius vermicularis in the appendix. AB - A total of 1590 human appendices were collected and examined histologically for evidence of pinworm infection. The incidence of infection in appendices was 2.39%. In examining 100 appendices by both the histological and the parasitological methods, 3 and 7 samples respectively were seen to be infected by pinworm. PMID- 8509625 TI - Studies on the attachment and penetration of hepatitis B virus. AB - There are two identified liver-specific attachment sites in the preS2 domain and one in the preS1 domain. Which mechanism leads to attachment in vivo is not known. The subsequent penetration seems to require proteolysis which does not occur spontaneously in HepG2 cells, but presumably in vivo. The role of the small HBs protein for attachment remains enigmatic so far, but it must have a function because an escape mutant exists against a monoclonal antibody which binds to an epitope of the small protein. The occurrence of this escape mutant in vaccinated persons proves that the standard hepatitis B vaccine does induce neutralizing antibodies, but it also suggests very strongly that the neutralizing preS epitopes be included in future hepatitis B vaccines. PMID- 8509626 TI - Liver transplantation in chronic viral B and C hepatitis. AB - Liver transplantation is a valid treatment in chronic viral B and C hepatitis. But disease recurrence is very frequent in HBV hepatitis after the procedure, and its prevention and treatment are unresolved problems. Hepatitis C recurrence in the graft seems also to be common, and further studies of its pathobiology are needed. PMID- 8509627 TI - Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. The TVVH Study Group. AB - Two hundred and thirty-four patients with chronic non-A, non-B hepatitis, 86% positive for anti-HCV by ELISA, were treated with recombinant interferon-alpha 2a or with natural (human-leukocytes-derived) interferon-alpha using different dosage and periods of administration. Interim analysis of follow-up data indicate that 65-70% of patients treated initially with 6 MU, thrice weekly, of recombinant interferon-alpha 2a achieved a complete biochemical response (normalization of alanine aminotransferase: ALT) during therapy compared to 56 58% of those treated with 3 MU, thrice weekly, of recombinant or natural interferon-alpha. A 12-month schedule of interferon administration appeared superior to a 6-month schedule in reducing the probability of reactivation of liver disease after therapy withdrawal, although further data are needed to confirm such a conclusion. The probability of response to interferon in terms of maintaining normal ALT after withdrawal did not appear to be influenced by sex, while it was significantly higher in patients aged below 45 years and in those without cirrhosis. PMID- 8509628 TI - Antiviral therapy of hepatitis C--present and future. AB - The current recommendations for therapy of chronic hepatitis C are a 6-month course of alpha-interferon in doses of 3 million units 3 times weekly. Patients should have compensated chronic liver disease with elevations in serum aminotransferases, serologic evidence of hepatitis C virus (HCV) infection and chronic hepatitis by liver biopsy. At present, a long-term beneficial response to alpha-interferon occurs in only 10-25% of patients. The modest long-term response rate and the restricted recommendations for use of interferon leave several unresolved issues regarding therapy of this disease. Do patients with atypical, severe or advanced disease warrant therapy? What is the optimal dose and duration of treatment? How can one increase the response rate to interferon? How can one predict which patients are likely to benefit from therapy? Which patients are likely to relapse if therapy is stopped? Ultimately, what is needed to answer these issues are better techniques to assess HCV infection and monitor therapy as well as more effective and better-tolerated agents that can be used alone or in combination with alpha-interferon. PMID- 8509629 TI - The problem of antiviral therapy for chronic hepadnavirus infections. AB - Attempts at antiviral therapy of patients with active liver disease as a consequence of chronic hepatitis B virus infection have been moderately successful. The molecular and cellular basis for a successful outcome in these patients is not understood and the same therapies do not appear to benefit carriers that still have fairly normal livers and only a moderate hepatitis as a result of the immune response to the infection. Most carriers fall into this latter classification, at least during the early years of infection, and a therapy that could be successfully applied before extensive liver damage had occurred would presumably reduce the risk of subsequent liver damage and the progression to primary hepatocellular carcinoma. Traditionally, it has been assumed that the primary reason that individuals become chronically infected is that the cytotoxic T-cell response and/or antibody-dependent killing of infected hepatocytes is insufficient to clear the infection. Less attention has been focused on the role of the antibody response in the generation of virus neutralizing antibodies as the possible major deficiency predisposing some individuals to become carriers. However, carriers normally are antigenemic for HBsAg and virus, and carriers with only antibodies to these structures in their circulation are virtually unknown. In addition, it is usually assumed that the hepatocyte, the major target of infection, does not spontaneously turn over and that, in the absence of an immune response to the infected cell, hepatocellular viability is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509630 TI - Animal models for the understanding and control of HBV and HDV infections. PMID- 8509631 TI - Pathobiology of hepatitis delta virus. AB - Early observations in humans and infectivity studies in the chimpanzee suggested a direct cytotoxic effect as the major pathogenetic factor in delta hepatitis. Data acquired in liver transplant patients, as well as additional experimental and clinical evidence, have modified this view and indicate instead that liver damage depends on several factors. To explain the array of different clinical presentations, the replication strategy of hepatitis delta virus, the helper function and genetic heterogeneity of the co-infecting Hepadnavirus, and the response of the host immune system should all be taken into consideration. PMID- 8509632 TI - Mechanisms governing hepadnaviral nucleocapsid assembly. AB - Reverse transcription of an RNA pregenome is the central step in the replication cycle of the hepatitis B viruses. This reaction takes place within the viral nucleocapsid composed of the core protein, product(s) of the P (pol) gene and the RNA pregenome. As the enzymatic activities required reside in the P-protein it plays a major role in the hepadnaviral life cycle. This article summarizes recent data on structure and function of the hepadnaviral P-protein and discusses its important role in the early steps of nucleocapsid assembly. PMID- 8509633 TI - Liver transplantation in cirrhosis due to hepatitis D virus infection. AB - In a series of 49 patients transplanted for cirrhosis due to hepatitis D virus (HDV) infection and receiving anti-HBs immunoglobulins, the 2-year actuarial rate of hepatitis B virus (HBV) reinfection was only 13%, a prevalence much lower than the 29% rate in patients transplanted for HBV-DNA-negative cirrhosis and the 96% rate in patients transplanted for HBV-DNA-positive cirrhosis. HBV reinfection after transplantation in patients with cirrhosis due to HDV infection was invariably associated with HDV reinfection. In a few patients, in the absence of HBV reinfection, transient replication of HDV took place and was not associated with liver lesions of hepatitis. In conclusion, patients with cirrhosis due to HDV infection are good candidates for liver transplantation. PMID- 8509634 TI - Significance of low HDV replication levels during the natural history of HDV infection. Long-term follow-up. AB - The use of genetic amplification of the hepatitis delta virus (HDV) genome reveals the existence of different HDV replicative behaviours during the natural history of chronic HDV infection. While some of the patients (8/19, 42%) presented high and long-term maintained levels of HDV replication, as detected by slot-blot hybridization, others showed fluctuations from positive to negative, and in 5/7 (71%) polymerase chain reaction (PCR) demonstrated the presence of the HDV genome. Finally, 4 patients were persistently slot-blot-negative and in 3 of them HDV-RNA was detected by PCR in all samples tested. The correlation observed between the low levels of HDV replication and the ALT values, as well as the reactivation observed in one of the patients, suggests that PCR is useful in the virological surveillance of HDV infection, and indicates its usefulness in evaluating the effectiveness of antiviral therapy for chronic hepatitis D. PMID- 8509635 TI - Regulation of hepatitis B virus gene expression. AB - Human hepatitis B virus (HBV) mainly infects hepatocytes. HB viral gene expression has been demonstrated to be liver-specific using DNA transfection methods. This liver-specific gene expression is regulated by promoter/enhancer elements. HBV contains two enhancer elements. Enhancer element I has been studied in detail at the DNA-protein level. This is further substantiated by DNA transfections of liver and non-liver cell lines with expression plasmids containing enhancer elements controlling the transcription of reporter genes. Genetic analysis of the enhancer elements defined the minimal sequences which play a key role in the regulation of enhancer function. One of the factors binding in this region is RXR alpha. Using only the DNA binding domain of the liver-specific RXR alpha expressed in E. coli, we demonstrated binding of RXR alpha to the putative retinoic acid receptor response element (RARE) in the HBV enhancer. Our studies implicate a potentially important role of retinoic acid and its receptor in the liver-specific regulation of HBV gene expression and the disease pathogenesis associated with infection. PMID- 8509636 TI - Characteristics of woodchuck hepatitis X-antigen in the livers and sera from infected animals. AB - This study tests the hypothesis that woodchuck hepatitis virus encoded X-antigen expression correlates with viral replication, with hepatitis, or with both. Paired liver and serum samples from each of 55 infected woodchucks were used. Seven of 8 carriers with high levels of viral DNA in serum also had X-antigen in serum. In contrast, the frequency of X-antigen in serum was low among infected woodchucks that did not have viral surface antigen in the serum. Statistical analysis showed a significant relationship between X-antigen in serum and markers of viral replication. Woodchuck hepatitis X-antigen (WHxAg) expression in liver but not serum of carriers closely correlated with the presence of hepatitis. The finding of X-antigen in the liver of infected animals with hepatitis that cleared the virus surface antigen from serum also suggests that X-antigen is associated with ongoing hepatitis. Hence, the persistence of WHxAg in serum may signal continuing viral replication and, in liver, may contribute to the pathogenesis of chronic infection. PMID- 8509637 TI - Polymerase chain reaction for the diagnosis of hepatitis B and C viral hepatitis. AB - The detection of HBV, HCV, and HDV genomes through the use of the polymerase chain reaction (PCR) has made possible a new step in viral diagnosis. The main advantages of PCR are its extreme sensitivity and the possibility to develop rapid assays using non-radioactive probes. Several studies have now clearly shown its usefulness for the demonstration of viremias, the identification of seronegative viral carriers, and studies on mother-to-child transmission. Several limitations, however, still hamper the use of PCR and it should not yet be regarded as a routine test. The main developments to be expected in the near future deal with automatisation, prevention of contamination, and quantification. PMID- 8509638 TI - To treat or not to treat? The judicious use of interferon-alpha-2a for the treatment of chronic hepatitis B. AB - Based on results from extensive clinical research, interferon-alpha-2a (IFN-alpha 2a, Roferon-A, F. Hoffmann-LaRoche Ltd., Switzerland) and other interferons have been registered for the treatment of chronic active hepatitis B. The officially recommended dose regimen is 4.5 MIU (or 2.5 MIU/m2) thrice weekly for 6 months. To present guidelines for the optimization of treatment for individual patients, 3 major controlled trials from our worldwide research program with a total of 416 patients were reviewed in a meta-analysis. Before deciding whether to treat or not, the history, prognosis and chances of treatment success for a given patient must be carefully assessed. Liver histology and repeated quantitative measurements of markers for viral replication (HBV-DNA, HBeAg) and biochemical markers for liver disease such as ALT are valuable indicators. After the decision to treat, monthly quantitative measurements of these markers make it possible to monitor therapeutic success. Depending on the course they run, treatment can continue unchanged, be adjusted in dose or duration until a full response is achieved, or be terminated early in case of evidence of non-response. PMID- 8509639 TI - Repeated courses of alpha-interferon for treatment of chronic hepatitis type B. AB - In chronic hepatitis B transition from active replication to viral latency (HBeAg seroconversion) usually leads to remission of the disease. alpha-Interferon (IFN) therapy induces HBeAg seroconversion in about one-third of the patients, thus leaving the majority of patients with persistent disease. Eighteen chronic hepatitis B patients who did not respond (HBeAg seroconversion and clearance of HBV-DNA) to an initial 16-week course of IFN subsequently received IFN again after at least 6 months of no therapy. The repeated therapy consisted of 1.5-5 MU lymphoblastoid IFN daily for 16 weeks. Treatment effects were monitored by quantitative measurement of HBeAg and HBV-DNA. To analyze whether the results were related to patient characteristics known to affect the response to initial treatment, a predicted response rate, based on pre-treatment factors, was determined. After a follow-up of 52 weeks, 2 of the 18 patients (11%) had responded to therapy. Two additional patients became HBV-DNA-negative with sustained HBeAg positivity. All patients remained HBsAg-positive. According to the pre-treatment parameters, a response was predicted for 9 of the 18 patients (50%). This predicted response rate was significantly higher than the actual response rate (p = 0.03). In conclusion, this pilot study with moderate dosages of IFN suggests that the HBeAg seroconversion rate after repeated IFN treatment is low for previous non-responders and probably is not related to important clinical characteristics that influence the response to initial IFN treatment. A large controlled trial with higher doses of IFN is desirable to further evaluate the benefits of retreatment. PMID- 8509640 TI - Treatment of chronic hepatitis B with interferon alpha-2b and interleukin-2. AB - A total of 37 patients with histologically confirmed chronic viral hepatitis B and presence of HBV-DNA and HBsAg in the serum were treated in a randomized, prospectively controlled multicenter trial either with recombinant IFN alpha-2b alone or a combination of IFN alpha-2b and recombinant IL-2. Twenty-two patients from group A were treated with 3 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Starting at month 2 IL-2 was added: priming doses of 1.5 million CU were given s.c. on the first 2 days of each of the remaining 3 months, followed by maintenance doses of 0.3 million CU daily for 5 days per week. Fifteen patients from group B received 5 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Five patients from group A (24%) and 4 patients from group B (28%) cleared HBV-DNA and HBeAg from the serum, and normalized elevated serum aminotransferase activities. The response rate in both groups did not differ significantly. Since side effects were more pronounced during combination therapy than in IFN alpha-2b monotherapy, it is suggested that treatment with IFN alpha-2b alone is preferable to a regimen of IFN alpha-2b/IL-2 applied according to the above schedule. PMID- 8509641 TI - Antiviral therapy of chronic hepatitis B: past, present, and future. AB - A wide variety of agents has been used to treat chronic hepatitis B, but none has proved effective with the exception of interferon. Toxicity has been a major problem with some drugs whereas in others a lack of antiviral potency has been demonstrated. Alpha-interferon represents a good compromise because it has both immunomodulatory and antiviral properties; moreover, it is generally well tolerated. Loss of HBeAg and hepatitis B virus DNA may be anticipated in 40-50% of patients who are treated with doses of 5 million units daily or 10 million units thrice weekly for 16 weeks. While drug-related adverse effects occur commonly, the majority of clinically stable patients are able to tolerate this regimen, and withdrawal from drug is necessary in approximately 5% of patients. Unlike the situation with chronic hepatitis C, loss of viral replication tends to be sustained years later. Disappearance of HBsAg only occurs in 10-15% of treated patients within the first year after therapy, but an increasing number of responders demonstrate HBsAg seroconversion upon prolonged follow-up. Hepatitis B virus DNA usually disappears from serum by polymerase chain reaction at the time of HBsAg loss. Low copy numbers of residual viral DNA are still detectable in liver tissue at this time, but this has uncertain significance. Marked improvement in histological features has been observed years after loss of HBsAg. Pre-therapy levels of circulating viral DNA and aminotransferase activity, degree of histologic activity, and HIV status appear to influence the response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509642 TI - Possible role of preS2 peptides presented by MHC class I antigen in the pathogenesis of chronic hepatitis B. AB - Many variations exist in the first 39 nucleotides of the preS2 (pre-S2; 1-39) region of the HBV genome. Based on the similarities of their coding amino acid sequences to those of prototype HBV, they were classified into 3 different types, adr-preS2, adw-preS2 and ayw-preS2. To clarify the meaning of these variabilities in the preS2 region, we studied the HLA class I phenotype of chronic hepatitis B patients having high levels of serum ALT. Our results indicated that in 12 of 14 chronic hepatitis patients infected with HBV type adr-preS2 had HLA-A24 phenotype whereas all of 7 patients infected with either adw- or ayw-preS2 HBV had HLA-A2 phenotype. This strong association between HLA class I phenotype and certain preS2 types of HBV infection was found only in patients with high serum ALT levels but not in patients with almost normal levels of serum ALT. Our results therefore suggest that in the generation of chronic hepatitis B a suitable combination between a fragment of preS2 antigen and HLA class I antigens of the infected host, such as adr-preS2 with HLA-A24 and either adw- or ayw-preS2 with HLA-A2, might be required. PMID- 8509643 TI - Epidemiology of hepatitis C virus infection. AB - The availability of the anti-HCV assay has confirmed most of the suspicions and predictions regarding the epidemiology of NANB hepatitis virus made before the discovery of HCV. It is now clear that HCV is responsible for the majority of cases of post-transfusion and sporadic NANB hepatitis, as well as of most cases of unidentified chronic liver disease. It seems plausible that HCV may act as a negative co-factor in other chronic liver diseases, especially those caused by alcohol, other hepatitis viruses, and so-called 'autoimmune hepatitis'. The issue of perinatal and sexual transmission of HCV has not yet been clarified, and further studies are urgently needed. Finally, the high prevalence of anti-HCV detected in HCC suggests that HCV is a major co-factor in the development of HCC and again raises the issue of viral persistence and neoplastic transformation, an issue that for HBV has not yet been elucidated. PMID- 8509644 TI - Hepatitis C virus infection and disease. Diagnostic problems. AB - Hepatitis C virus (HCV) is a lipid-enveloped single-stranded RNA virus with an unknown physical structure as only putative HCV particles have been identified by electron microscopy. Although HCV lacks the retroviral properties of being able to integrate into host DNA, it causes chronic infection in a considerable number of infected individuals (40-60%). Chronic infection is associated with a wide spectrum of liver diseases ranging from normal presentation to the different forms of chronic hepatitis, cirrhosis (about 20% of cases) and hepatocellular carcinoma. HCV therefore is not invariably and equally pathogenic, and genetic heterogeneity could be a major cause of such variability. Diagnosis of HCV infection relies on anti-HCV and HCV-RNA detection. Using second-generation assays, diagnostic sensitivity has increased to about 95%, but detection of anti HCV does distinguish past from present infections. Only rising anti-HCV titres or anti-HCV seroconversion confirm a recent HCV infection. In anti-HCV-negative infections and cases of early acute hepatitis, HCV-RNA detection by RT-PCR represents a valid diagnostic alternative. In patients undergoing interferon therapy, testing for anti-HCV by immunoblotting represents a valid routine tool to monitor response. Anti-C-22 has the highest titre and persists longer while anti-C-100 is the earliest antibody to disappear in responders. The significant association between serum anti-C-100, HCV-RNA and liver disease suggests that anti-C-100 is an indirect marker of hepatitis C, but true markers of HCV-induced liver disease are still lacking. PMID- 8509645 TI - Routine laboratory diagnosis of hepatitis C virus infection. AB - Hepatitis C virus (HCV) is the major cause of parenterally transmitted non-A, non B hepatitis. The analysis of the genomic sequence of HCV has facilitated the development of a number of diagnostic assays for testing circulating antibodies in serum from patients with HCV infection. Besides the first-generation ELISA and RIBA, which employed the C100-3 non-structural polypeptide, second-generation tests employing both structural and non-structural polypeptides are being rapidly introduced. Several coded panels were employed in a comparative study of HCV-SP ELISA (utilizing a new synthetic peptide whose sequence was derived from the structural region) along with first- and second-generation tests. On the basis of the results, evidently antigens corresponding to the structural components of the virus are more sensitive and specific for the early detection of HCV antibodies than tests using non-structural epitopes. Additionally epitopes of the structural region elicit a very strong antibody response in laboratory animals. An example of one such application is the detection of HCV specific antigens in semen from patients diagnosed with non-A, non-B (NANB) hepatitis. Semen samples from 9 patients clinically diagnosed as having NANB hepatitis were tested by an ELISA using antibodies against HCV-specific structural antigens. The semen from all 9 patients had HCV-specific structural antigens in comparison to semen from 5 healthy donors. Semen from 5 of the 9 patients had significant levels of the HCV specific antigen. This approach to detecting HCV antigens could, if rigorously tested, evolve into promising new assays for detecting HCV. PMID- 8509646 TI - A rapid and simple microfluorometric phagocytosis assay. AB - A microfluorometric method for phagocytosis study has been developed using fluorescein conjugated Escherichia coli K-12 particles. This technique is based on the uptake of fluorescent particles and quenching of extracellular fluorescence at the end of the assay. A murine macrophage cell line, J774, was used as a phagocyte model. The cells were harvested from tissue culture flasks and adjusted to 1 x 10(6) cells/ml. They were then dispensed into a 96-well tissue culture plate, 100 microliters/well, and incubated at 37 degrees C in 5% CO2 for 1 h to allow cells to adhere to the bottom of the wells. The culture medium was aspirated and 100 microliters of fluorescent E. coli particles suspended in Hanks' buffer were added. The plates were further incubated for various time periods. Buffer solution in the wells was removed by aspiration. Extracellular fluorescence was then quenched by adding 100 microliters of trypan blue (250 micrograms/ml, pH 4.4). The dye was removed after 1 min. The intensity of fluorescence associated with intracellular fluorescent particles was measured directly in the wells using a computerized microplate fluorometer at 485 nm excitation and 530 nm emission. This assay provided a rapid and objective measurement of phagocytosis activity. Using a cultured cell line and a 96-well microtiter plate format, this assay can facilitate the screening of a large number of various biological and pharmacological substances for their modulating effects on phagocytosis. PMID- 8509647 TI - Abdominal wall thickness as a means of assessing peritoneal fibrosis in mice. AB - Herein we describe a method for the quantitative assessment of connective tissue deposition within the peritoneal cavity. Female C57BL/6 mice (8-10 weeks) were given a single intraperitoneal injection of varying concentrations of talc (100 mg, 50 mg, 30 mg, 20 mg) in 1 ml of PBS or PBS alone. After 14 days, animals were killed. Adhesion formation was measured by the standard method of Myllarniemi et al. (1966), namely a gross visual inspection of the peritoneal cavity. This analysis gave a crude assessment of connective tissue deposition in the abdominal cavity but did not allow one to distinguish more subtle differences between intermediate dosage groups. In addition, a histological evaluation was performed. For the latter method, portions of the abdominal wall of mice were fixed and processed for histological analysis using Masson's Trichrome stain which allows for differentiation of connective tissue components. The thickness of connective tissue between the parietal peritoneum and the underlying abdominal wall muscle was measured. A dose-dependent increase in connective tissue deposition was observed in talc-treated animals compared to saline control animals. A differential cell count of the peritoneal exudate cells (PEC) showed that there was no change in cell populations in talc treated animals (compared to control animals). Given the above results, the measurement of connective tissue thickness was found to give the most accurate assessment of peritoneal fibrosis than other previously used methods. PMID- 8509648 TI - Simple method for the preparation of antigen emulsions for immunization. AB - We have developed a rapid, safe, and reliable method to prepare emulsions of water-soluble antigens in an adjuvant oil phase for immunization purposes. The method, based on well established emulsification principles, employs a three-way 'T' connector to which three disposable syringes are attached. The system allows the stepwise addition of small volumes of the water phase, into the oil phase. We have compared the time required for emulsification, the rate of antigen release from the emulsion into a physiological phase, and the immunogenic properties of bovine serum albumin and transferrin contained in emulsions made by the new stepwise addition method, with those made by the widely used double-hubbed needle method. We report a significantly shorter (P < 0.001) and a more reproducible emulsification time for the stepwise addition method (6.1 +/- 2.1 min; mean +/- SD) than for the double-hubbed needle method (41.1 +/- 28.0 min). The stepwise addition method always yielded water-in-oil emulsions, while the double-hubbed needle method failed, about 20% of the time, to produce a water-in-oil emulsion after 120 min of mixing. Since the stepwise addition method employs a connector with a larger inner diameter (1.75 mm) than the one required for the double hubbed needle method (0.84 mm); the pressure required for the former is markedly reduced compared with that required for the latter, thus making the new method safer and less labor-intensive. The rate of antigen release from the emulsions was significantly slower when the stepwise addition method was employed (P < 0.01). There were no differences in viscosity and stability in the emulsions prepared by the two methods. The ability of antigen-containing emulsions to elicit an immune response was found to be identical by the two methods; no significant differences were found in antibody titers as determined by enzyme linked immunosorbent assays. These characteristics make the stepwise addition system the method of choice. PMID- 8509649 TI - New flow cytometric method for surface phenotyping basophils from peripheral blood. AB - To clarify the role of basophils in the pathogenesis of allergic disease, we developed a new method for performing surface phenotyping of these cells in centrifugation-enriched mononuclear cell fraction. This method identified basophils on the basic of a negative reactivity with mixed FITC-conjugated monoclonal anti-bodies (mAbs) (anti-CD2, -CD14, -CD16, and -CD19) with analysis performed by flow cytometry. The validity of this approach was confirmed by sorting experiments. Various PE-conjugated mAbs were also used to examine binding to FITC-negative basophils. Basophils from asthmatic patients (n = 14) as well as from normal subjects (n = 6) were shown to express CDw32 (Fc gamma RII), CD25 (IL 2R), but not CD64 (Fc gamma RI). We also detected binding of IgG1 and IgG4 to basophils. This method of phenotyping was very rapid and simple. It thus appears to be useful in the study of allergic disease, as well as of the biology of the basophil. PMID- 8509650 TI - Highly sensitive fluorimetric enzyme immunoassay for prostaglandin H synthase solubilized from cultured cells. AB - A highly sensitive fluorimetric enzyme immunoassay was developed for prostaglandin H (PGH) synthase, an intrinsic membrane protein, using n-octyl beta D-glucopyranoside for solubilization of the synthase from the endoplasmic reticulum membrane. An anti-PGH synthase IgG-coated polystyrene ball was reacted with a PGH synthase standard or crude detergent extract of cells, washed to remove the detergent, and then incubated with anti-PGH synthase Fab'-beta-D galactosidase conjugate. The bound beta-D-galactosidase activity was quantitated with 4-methylumbelliferyl-beta-D-galactoside, a fluorogenic substrate. The detection limit for the PGH synthase standard was found to be 1.0 pg/assay. The sensitivity of this assay is increased by about 2-3 orders of magnitude over those of previously reported radioimmunoassay or colorimetric enzyme immunoassay. The high sensitivity of the fluorimetric enzyme immunoassay allowed reliable detection of low levels of human PGH synthase present in small samples of cultured cells. Our studies with this fluorimetric immunoassay for the synthase developed a general method for determination of membrane-bound proteins at ultrasensitive levels. PMID- 8509651 TI - Detection of anti-pituitary autoantibodies by immunoblotting. AB - A new approach to the detection of anti-pituitary autoantibodies by immunoblotting is presented. This method distinguishes pituitary membrane fraction from cytosolic fraction autoantigens and characterizes them by their molecular weight. A 45 kDa pituitary specific membrane protein was identified as an autoantigen in one of 19 patients with idiopathic growth hormone deficiency and the empty sella syndrome. A 43 kDa membrane protein in pituitary and brain was identified as an autoantigen in one other patient with idiopathic growth hormone deficiency and in one of 14 patients with secondary growth hormone deficiency. These autoantibodies were not seen in any of 27 control subjects. Anti-pituitary autoantibodies can be demonstrated by immunoblotting at titres of up to 1/1000. We conclude that immunoblotting is a useful method for the detection of anti-pituitary autoantibodies. PMID- 8509652 TI - Immunoassay reagents for psychoactive drugs. I. The method for the development of antibodies specific to amitriptyline and nortriptyline. AB - Amitriptyline and nortriptyline were structurally modified by the attachment of spacer arms to the aromatic ring which were subsequently attached to bovine serum albumin (BSA). Rabbits inoculated with these conjugates yielded polyclonal antisera with high selectivity and good titers. This approach required novel spacer arms and new conjugation methods. The antisera produced were characterized with respect to their cross-reactivity with amitriptyline, nortriptyline and their hydroxy metabolites as well as selected structurally related compounds. PMID- 8509653 TI - Fast immunopurification of small amounts of specific antibodies on peptides bound to ELISA plates. AB - ELISA is widely used as a means to detect antibodies, but the potential of ELISA plates as an immunosorbent for the purification of specific antibodies does not seem to have been evaluated. In this study, ELISA plates coated with peptides representing short sequences of various antigens from Plasmodium falciparum, the etiologic agent of human malaria, have been successfully used as a means to purify small amounts of the corresponding antibodies. ELISA plates, identical to those used for antibody detection, also permitted the evaluation of various elution conditions for each pairing of peptide and serum; we tested four eluting buffers (0.2 M glycine, pH 2.5; 0.2 M lysine, pH 11.5; 3.0 M MgCl2, 0.075 M Hepes, 25% ethylene glycol, pH 7.1-7.2 and 4 M NH4SCN in 0.1 M NaH2PO4, pH 6.0) with four pairs of peptides and sera. The ELISA plates could also be used to estimate the affinity of the eluted antibodies by the technique of Pullen et al. (1986). The eluted antibodies were compared to those obtained by immunopurification on recombinant proteins adsorbed on nitrocellulose filters. In contrast to the latter, they were not contaminated by antibodies directed against the carrier moiety of the recombinant protein. When used in immunofluorescence assays with various stages of the parasite the antibodies immunopurified on peptides bound to ELISA plates were able to react with the native antigens in the parasite. PMID- 8509654 TI - Quantitation of monoclonal antibodies by ELISA. The use of purified mouse IgG and mouse IgM monoclonal antibodies as standards in a quantitative ELISA measuring monoclonal antibodies produced by cell culture. AB - Murine monoclonal antibodies (MAbs) of IgG1, IgG2a and IgG2b subclasses and IgM class in hybridoma culture supernatants were quantified using a sensitive, reliable, optimized indirect double antibody sandwich ELISA. In the ELISA, the MAb in the culture supernatants was sandwiched between affinity isolated heavy chain specific polyclonal antibodies used for capture and detection. Quantitation was achieved by comparison with a standard curve produced by a purified MAb of the same class, subclass or ideally the same clone as the MAb to be quantified. These quantitative results were compared with those obtained using purified IgG and IgM polyclonal serum samples as standards and those obtained by total protein estimation using measurement at OD280nm. The IgG subclass MAbs used as standards were purified using protein G and the IgM class MAb was purified by ion exchange followed by gel filtration chromatography. Bovine IgG contamination of the MAb supernatants and the purified MAbs was also measured by a double antibody sandwich ELISA. PMID- 8509655 TI - Immunologic detection and measurement of glycated apolipoprotein B with site specific monoclonal antibodies. AB - Nonenzymatic glycation of apolipoprotein B (apo B) is a post-secretory modification of low density lipoprotein (LDL) that affects its atherogenic potential and is implicated in the accelerated atherosclerosis associated with diabetes. To facilitate assessment of apo B glycation, we produced hybridomas secreting monoclonal antibodies specific for glycated apo B. SP 2/0 myeloma cells were fused with spleen cells from BALB/c mice immunized with purified apo B glycated non-reductively in vitro. Specificity of monoclonal antibodies secreted by the cloned cell line designated ES12 was demonstrated by immunoblotting and by direct ELISA, wherein the antibodies reacted with glycated epitopes residing in LDL but not in other plasma proteins, and did not react with nonglycated apo B or nonglycated LDL. Immunoblotting of human plasma with ES12 monoclonal antibody yielded an approx. 180,000 molecular weight component showing co-identity with apo B, indicating site specificity for glycated epitopes residing in apo B of the LDL complex and absence of reactivity with other nonenzymatically glycated plasma proteins. This reactivity of ES12 with the physiologic form of glycated apo B that occurs in vivo differs from properties of other antibodies raised against glycated lipoproteins, which recognized glycated residues only after reductive conversion to glucitol-lysine and which do not discriminate between different glycated proteins. In a competitive ELISA, mean concentration of glycated LDL, measured as apo B equivalents, in eight separate plasma samples was 19.7 +/- 1.9 micrograms/ml, representing 3.5 +/- 0.3% of total apo B. The ES12 monoclonal antibody allows specific determination of plasma glycated LDL concentrations, which may have diagnostic and pathogenetic importance. PMID- 8509656 TI - Measurement of murine ovalbumin-specific IgE by a rat basophil leukemia cell serotonin release assay. Comparison to the rat passive cutaneous anaphylaxis assay. AB - A modified in vitro method to measure murine ovalbumin-specific IgE antibody as an alternative to the in vivo rat passive cutaneous anaphylaxis assay is presented in this report. This assay uses rat basophil leukemia (RBL) 2H3 cells that have been loaded with [3H]serotonin. Exposure of RBL-2H3 cells to mouse antisera and subsequent antigen challenge results in the release of [3H]serotonin. Using a monoclonal mouse anti-DNP IgE antibody and DNP-human serum albumin as the antigen, various steps of this assay were optimized to decrease the amount of time and reagents needed for the assay. The percent [3H]serotonin released was used to calculate antibody titer of sera from ovalbumin-immunized mice. Mouse anti-ovalbumin IgE titers determined by the RBL release method and passive cutaneous anaphylaxis assay were found to correlate very well over a wide range of antibody titers (correlation coefficient, r2 = 0.94). PMID- 8509657 TI - Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults. AB - A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions. PMID- 8509658 TI - Pharmacokinetics and antiviral activity of recombinant human interferon-beta ser17 in African green monkeys. AB - The pharmacokinetics and antiviral activity of recombinant human interferon-beta ser17 (Betaseron) were evaluated in African green monkeys. In one study, animals infected with simian varicella virus were administered Betaseron intravenously (i.v.), intramuscularly (i.m.), or subcutaneously (s.c.) at doses of 1 x 10(6) or 1 x 10(7) IU/kg twice daily for 10 days. In another study, infected animals received Betaseron s.c. at doses of 1 x 10(6) IU/kg twice daily, 2 x 10(6) IU/kg once daily, 4 x 10(6) IU/kg every other day, or 6 x 10(6) IU/kg every 3 days for 10 days. Following i.v. administration, mean clearance, steady-state volume of distribution, and terminal half-life values for Betaseron were 0.36 +/- 0.08 liters/hr.kg, 0.65 +/- 0.09 liters/kg, and 1.9 +/- 0.43 h, respectively. Although bioavailability following i.m. and s.c. administration was only 30-50%, antiviral activity, as measured by reduction in viremia and appearance of skin rash, was comparable for i.v., i.m., and s.c. administration of 1 x 10(6) IU/kg of Betaseron twice daily. With increasing dose (1 x 10(6) IU/kg to 1 x 10(7) IU/kg), both the area under the serum concentration-time curve (AUC) and antiviral activity of Betaseron tended to increase. When comparing various s.c. dosing regimens, there was significant accumulation of Betaseron in serum with repeated twice-daily dosing. However, no accumulation of Betaseron in serum was observed if the dosing interval was less frequent than once daily. Antiviral activity was greatest with twice-daily or once-daily s.c. administrations of Betaseron. PMID- 8509659 TI - Amino acid substitutions alter the tissue distribution of murine interferon-alpha 1. AB - Novel analogs created by site-directed mutagenesis of murine interferon-alpha 1 (IFN-alpha 1) were used to examine the effect of alterations in structure and biological activity of murine IFN-alpha 1 on tissue distribution in mice. The analogs were biosynthetically labeled with [35S]methionine using a cell-free transcription-translation system and injected intravenously into adult male BALB/c mice. Levels of murine IFN-alpha 1 (dpm/gram wet weight) were highest in the liver, spleen, kidney, and lung, lower in the heart, and quite low in testis, brain, skin, and muscle. The tissue distribution of the analogs differed from that of murine IFN-alpha 1. In general, analogs with reduced antiviral activity showed reduced uptake by the spleen and lung. The amount in the kidney of the analog R33E, which has no detectable antiviral activity in vitro, was substantially higher than that of native IFN, suggesting a greater rate of excretion of this analog. An analog of human IFN-alpha 4, which had increased antiviral activity on murine cells, showed increased uptake in the liver, spleen, and lung. These findings, together with the results of a previous study using autoradiography (Johns et al., 1990, Cancer Res. 50, 4718-4723) indicate that nonspecific uptake by parenchymal cells in the liver, spleen, and lung is unaffected by changes in antiviral activity, while specific, receptor-mediated localization of IFN in regions rich in macrophages is reduced in accordance with the reduction in antiviral activity. PMID- 8509660 TI - Production and characterization of recombinant canine interferon-gamma from Escherichia coli. AB - We have used the recently cloned cDNA for canine interferon-gamma (IFN-gamma) to engineer bacteria to produce large amounts of the recombinant cytokine. The resulting protein can be recognized by monoclonal and polyclonal antibodies largely species specific for canine IFN-gamma. The purified recombinant IFN-gamma (rIFN-gamma) also had biological activity in vitro in three assay systems: (i) vesicular stomatitis virus plaque inhibition, (ii) class II major histocompatibility complex antigen upregulation on canine kidney parenchymal cells, and (iii) amplification of in vitro tissue-associated lymphoproliferation, all known to be effected by native IFN-gamma (nIFN-gamma). The availability of large amounts of active canine rIFN-gamma will be an important tool in studies of the role of this cytokine in the widely used experimental canine organ transplant model and also will be of diagnostic and therapeutic veterinary interest. PMID- 8509662 TI - Application of the model-positioning appliance for three-dimensional positioning of the maxilla in cast surgery. AB - During cast surgery the model-positioning appliance allows a controlled three dimensional positioning of the maxillary incisors and of the entire maxilla in one- or two-jaw surgery. The model-positioning appliance is fastened, in place of the incisal pin or the incisal table, to the anterior end of the upper part of a semiadjustable articulator. Three reference points are marked with a pencil directly on three maxillary teeth. The reference plane during cast surgery is the hinge axis-infraorbital plane, which is represented by a parallel to the upper part of the articulator. All measurements during cast surgery are parallel or at a right angle to this reference plane. Three-dimensional adjustment of the maxillary cast is possible without measurements with a ruler and without the marking of reference points and drawing osteotomy lines on the base of the cast. Sawing cuts on the base of the cast corresponding to marked osteotomy lines is avoided. In this way errors are reduced and precision is increased. The advantage of model-positioning appliance is that the three reference points on the maxillary teeth can be adjusted simultaneously and that the relation of the whole maxillary dental arch to the mandibular dental arch can be controlled at the same time. PMID- 8509661 TI - Stable conformation of an interferon-gamma receptor binding peptide in aqueous solution is required for interferon-gamma antagonist activity. AB - A peptide antagonist for mouse interferon-gamma (IFN-gamma) activity corresponding to the amino-terminal 39 amino acids of mouse IFN-gamma [MuIFN gamma (1-39)] has been identified previously. In an analogous manner, we have assessed the ability of the corresponding peptide of human IFN-gamma [HuIFN-gamma (1-39)] to antagonize human IFN-gamma. HuIFN-gamma (1-39) has the ability to block the antiviral activity of human IFN-gamma in a functional assay. In receptor competition, the peptide can also block human IFN-gamma receptor binding. Surprisingly, the murine analog, MuIFN-gamma (1-39), possesses a 10-fold greater ability to block human IFN-gamma antiviral activity and receptor binding than HuIFN-gamma (1-39). Both peptides showed alpha-helical structure in water by circular dichroism, however MuIFN-gamma (1-39) possessed a greater amount of alpha-helix compared to HuIFN-gamma (1-39), suggesting a requirement for a stable secondary structure for optimal antagonist activity. In trifluoroethanol, a helix stabilizing agent, both peptides showed relatively equal alpha-helices, suggesting that both sequences have an equal potential for helical structure. As IFN-gamma is species specific, the observation that MuIFN-gamma (1-39) can antagonize human IFN-gamma raises questions about the role of this region in species specificity. These studies provide insight into the structural requirements, both primary and secondary, for IFN-gamma receptor binding. In the future, this information, along with more detailed three-dimensional structural analyses of the peptides, could prove useful in the rational design of IFN-gamma agonists and antagonists. PMID- 8509663 TI - A new technique of alar base cinching following maxillary osteotomy. AB - Alar base cinching for the correction of flat and flaring noses was first described about 10 years ago. Its use to correct, without the use of skin incisions, nasal base flaring that results from Le Fort I osteotomy has also been reported. The use of the nasotracheal tube in orthognathic surgery hampers or otherwise affects the use of alar base cinch sutures. A technique is described to effect alar base cinching in a more predictable manner. PMID- 8509664 TI - Modified mandibular body step osteotomy-ostectomy. AB - The mandibular body osteotomy, introduced in 1906, remains a versatile operation with predictable results. In this paper, a modification of the mandibular step osteotomy-ostectomy and its use in two patients are described. PMID- 8509665 TI - Patterns of nerve regeneration in dental pulps of monkeys following surgical transection at 1 year. AB - Previous studies have reported revascularization and reorganization of dental pulp chambers with periodontal tissues of monkeys following complete surgical transection through a portion of the apical roots. This study observed 128 teeth in four adult monkeys. Following surgical transection, the tissues were acquired by perfusion fixation, serially sectioned, and stained for cellular detail with hematoxylin and eosin. Collagen tissues were stained with Preece's trichrome and neural tissues with Rowles' silver cyanate for controlled impregnation. At 1 and 2 weeks the coronal tissues showed tissue disruption, necrosis, and degenerating nerves. The 3- and 4-week tissues that had been completely transected showed replacement healing of the pulp tissue with periodontal ligament connective tissue, but no nerves were present. At 6 weeks, no nerves were present in the coronal chambers of those teeth with complete vital transection. The 24-, 36-, and 52-week pulp chambers with complete transection failed to show nerve fibers in their reorganized connective tissues. PMID- 8509666 TI - Surgical-orthodontic treatment in hemifacial hypertrophy: a case report. AB - Marked facial asymmetry caused by unilateral enlargement of hard and soft tissues is the criterion for a diagnosis of hemifacial hypertrophy. A case report of a Thai woman with congenital hemifacial hypertrophy is presented. Orthodontic treatment and intraoral vertical ramus osteotomies were performed after growth ceased. Acceptable facial appearance and occlusion were achieved. PMID- 8509667 TI - Changes in the nasal and labial soft tissues after surgical repositioning of the maxilla. AB - Accurate prediction of postsurgical function and esthetics of the nose and upper lip requires an understanding of the relationship between maxillary surgical movement and soft tissue change. Thirty-two patients underwent Le Fort I osteotomies, some with concomitant mandibular procedures. Preoperative, postoperative, and 1-year postsurgical data derived from cephalometric and nasolabial cast analysis were compared to assess skeletodental changes, soft tissue changes, and stability. A multiple stepwise regression (including age, gender, alar cinch suture, V-Y closure, and contouring of the anterior nasal spine as variables) indicated that accurate prediction equations could be formulated, particularly if the patients were grouped by vector-specific maxillary movements. In general, the base of the nose widened in all patients regardless of the vector of surgical maxillary movement. An associated shortening of the nose was found. The nasolabial angle decreased or remained constant in most patients. The upper lip widened and lengthened at the philtral columns. Narrow noses widened more than did broad noses and alar cinch suturing widened the alar base even more. Results indicated that soft tissue changes associated with maxillary surgery may be more affected by the position of the soft tissue incision and methods used in closure than by the surgically induced hard tissue change. PMID- 8509668 TI - [Significance of amniotic fluid cytokines measurement in threatened preterm labor and premature rupture of the membranes]. AB - The purpose of this study was to elucidate the significance of measurements of cytokines in the amniotic fluid. Amniotic fluid was retrieved by transabdominal amniocentesis from 113 women in the following groups: Preterm labor (N = 58), PROM (N = 21) and term elective C/S (N = 34). Tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta), were measured with a commercially available ELISA. Interleukin-6 (IL-6) was measured by bioassay and newly developed "luminescencer EIA". 1. Amniotic fluid concentrations of TNF-alpha, IL 1 beta and IL-6 in cases of term elective C/S were 22.8 +/- 19.2 pg/ml, 8.1 +/- 5.2 pg/ml and 166.8 +/- 126.1 pg/ml, respectively. 2. Significantly higher levels of TNF-alpha, IL-1 beta, IL-6 were found among the cases who failed to respond to tocolysis (i.e. delivery within 48 hrs of amniocentesis). In contrast, no significant difference in such conventional markers of infection as maternal serum CRP was noted. 3. According to the degree of histopathologic chorioamnionitis (Blanc), significantly higher concentrations of IL-1 beta, IL-6 were found among the of stage III cases than those in stage II irrespective of the rupture of the membranes (IL-1 beta: 1.36 +/- 0.41 ng/ml vs 76.6 +/- 20.1 pg/ml, IL-6: 31.98 +/- 4.55 ng/ml vs 5.22 +/- 0.92 ng/ml). Significant correlation was also found between the concentrations of IL-1 beta, IL-6 and the pathological degree of funitis (Nakayama, stage 0 < stage I, stage II < stage III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509669 TI - [Antitumor effect of PSK and its combined effect with CDDP on ovarian serous adenocarcinoma-bearing nude mice]. AB - Although the antitumor effect of PSK can be increased by potentiating the immune functions of PSK in tumor-bearing hosts, the mechanisms of its action are not fully understood. In this study, we examined the antitumor effect and CDDP combined effect of oral administration of PSK on nude mice bearing a human ovarian cancer cell line (KF cells). 1. PSK was observed to have a significant antitumor effect in tumor-bearing nude mice and subsequently to bring about an increase in the survival rate and prolongation of the life span. 2. The antitumor effect of CDDP was (but not significantly) enhanced by oral administration of PSK and the prolongation of the life span of the tumor-bearing nude mice was obtained. 3. Six weeks after tumor inoculation, no significant natural killer (NK) cell activity in spleen cells from untreated nude mice was observed. However, when PSK (100 mg/kg but not 500 mg/kg) was given every other day, significant NK activity was induced. 4. The serum immunosuppressive acid protein (IAP) value in nude mice treated with PSK alone was significantly higher than that in nude mice treated with a combination of PSK (100 mg/kg) and CDDP. These results suggest that CDDP prevents the increase in serum IAP that occurs when PSK is used and that consequently combinations of PSK and CDDP result in augmentation of antitumor effects. PMID- 8509670 TI - [A study on tissue inhibitor of metalloproteinases (TIMP) during pregnancy and at delivery]. AB - Metabolism of collagen in the fetal membrane has been proposed as one of causes of premature rupture of the membrane (PROM). It mainly depends on the activities of MMPs and their inhibitor, TIMP. The concentration and localization of TIMP in various body fluids and the tissue of perinatal patients was explored. 1. The TIMP concentration in maternal serum did not show any significant changes during pregnancy, and it was not significantly different from that in non-pregnant serum. In cases of PROM (n = 9) and premature labor (n = 4), there were no differences in the serum levels of TIMP. 2. The mean TIMP value in amniotic fluid was 754 +/- 325 ng/ml. There was no correlation between TIMP and gestational weeks. 3. The level of TIMP at delivery in amniotic fluid was significantly (p < 0.01) higher than that in maternal serum and umbilical serum, but it was not detected in neonatal first voided urine. 4. The mean TIMP values in amnion and chorion were 84 +/- 53 and 48 +/- 22 ng/mg protein respectively, but it was not detected in fetal lung or skin. 5. TIMP was clearly localized in fetal membrane, amniotic epithelium, amniotic fibroblast, chorionic epithelium and decidua, as detected by the immunohistochemical method. These results indicate that the higher level of TIMP in amniotic fluid originates in the fetal membrane. PMID- 8509671 TI - [Clinical study of pregnant women with psychotic disorders during last 14 years in Osaka Medical College]. AB - The clinical features and outcomes of 51 pregnancies (47 patients) complicated by psychotic disorders were studied. These patients were diagnosed as having the following psychotic disorders: 7 schizophrenias, 8 atypical psychoses, 6 mood disorders, 25 epilepsies, 4 anxiety disorders, and 1 personality disorder. The mean delivery age of women suffering from schizophrenia, atypical psychosis, and anxiety disorder was over 30 with deliveries 7-10 years after the onset of their psychoses. The predominant obstetrical complications for schizophrenias, atypical psychoses, and mood disorders were gestational toxicosis, threatened premature birth, and premature birth, respectively. Six out of eight (75.0%) patients with atypical psychosis, 4 out of 6 (66.7%) patients with mood disorder, and 2 of 4 patients with anxiety disorder became worse during pregnancy and/or postpartum. The rate of deterioration of the patients with schizophrenia was 14.3% (1/7) during pregnancy. An increasing rate of epileptic attack during pregnancy and/or postpartum were observed in 40.0% (10/25) of patients. Nine cases underwent cesarean section not due to their mental disorders but for obstetrical reasons. The present study suggests that the cooperation between obstetrician and psychiatrist, and the existence of a key person who knows the patient very well is required for a desirable outcome of the treatment. PMID- 8509673 TI - [A study on the integration of fetal behavior and the development of association between parameters evaluated]. AB - To evaluate the development of the fetal behavioral state with reference to the association of the fetal parameters we selected, we simultaneously monitored fetal heart rate (FHR), fetal movement (FM), fetal eye movement (FEM) and fetal breathing movement (FBM). These various parameters were monitored with 2 ultrasonographic real time scanners and a doppler device to monitor fetal movement. We assessed the convergence and integration of these four parameters to evaluate the association rate (AR). FHR with a variation in excess of 3 min. was interpreted as the active phase (A), and reduced variation in excess of 3 min. as the inactive phase (I). When FM and FEM were observed in the 1 min. window of A, we labeled this A3, and when FBM was present in more than 10% of the 1 min. window, we labeled it A4. A3/A = AR-A3% and A4/A = AR-A4% was calculated. A similar calculation was done for I, without FM and FEM in the 1 min. window of I (I3) and when FBM was present less than 10% of 1 min. (I4), allow derivation AR I3% and AR-I4%. A discrete separation of synchrony in A and asynchrony in I can be seen to develop as the fetus matures, and we feel that this may be a valuable tool in the evaluation of fetal central nervous system development in utero. PMID- 8509672 TI - [Twenty one multicentral studies on prognosis of advanced ovarian cancer; focused on correlation between primary surgical procedure following adjuvant chemotherapies and 4 year survival rates]. AB - The treatment outcome of 778 patients with stage III ovarian cancer treated by surgery and chemotherapy between 1976 and 1990 in 21 institutions was analyzed retrospectively. Survival of patients treated between 1985 and 1990 was significantly superior to that before 1985 (Kaplan-Meier, p < 0.01). Four year survival rates were found to be distributed from 5 to 52% among institutions (p < 0.001, log-rank test). When survival rates were compared according to the relative dose intensity (RDI) of CDDP administered, patients who were given CDDP RDI > or = 0.9 had a favorable prognosis. The twenty-one institutions were divided into two groups: Standard (total abdominal hysterectomy and bilateral salpingo-oophorectomy) vs. standard+debulking (of as much gross tumor as can safely be performed) according to the operative procedure which was performed in each hospital. It was found that the four-year survival rate for patients treated in hospitals where standard surgery was done was 22.9 +/- 12.2%, whereas that in hospitals adopting standard+debulking surgery was 34.4 +/- 10.1% (p = 0.03, t test). When the hospitals were divided into 4 groups according to combination of the operative procedure and CDDP RDI, the four year survival rates were 17.5 +/- 8.3% for standard+debulking+CDDP RDI < 0.9, 39.0 +/- 1.4% for standard+CDDP RDI > or = 0.9, 28.8 +/- 11.5% for standard+debulking+CDDP RDI < 0.9 and 37.8 +/- 8.0% for standard+debulking+CDDP RDI > or = 0.9.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509674 TI - [A case of carcinoma of the uterine cervix accompanied with paraneoplastic cerebellar degeneration]. PMID- 8509675 TI - [A case of cor triatriatum diagnosed in pregnancy]. PMID- 8509676 TI - Nursing implications of visual fields in successfully treated retinoblastoma patients. AB - Very little data has been published on the long term peripheral vision of patients diagnosed and successfully treated for retinoblastoma. Nursing should address the patient's response to vision-conserving treatment and their adaptation to decreased peripheral vision. Computerized Humphrey's Central 30/Peripheral 30-60 visual fields were performed on ten patients (all with greater than ten year follow-up) who were successfully treated for retinoblastoma. All ten visual fields revealed an absolute and relative scotoma in the affected eye. Visual field loss was always worse than one would have predicted based upon the fundus examination of the tumor(s). Decisions for treatment must be based upon an interdisciplinary approach of nursing and medicine to evaluate patient survival and visual outcome. Nursing interventions include utilizing the visual field as a teaching aid, preparing the patient and the family for potential future visual loss and adaptation of lifestyle, and providing emotional support and realistic reassurance. PMID- 8509678 TI - Sensory nursing. PMID- 8509677 TI - Surgical experience of the ophthalmic patient. AB - The role of the ophthalmic nurse is vital to patient continuity of care. By acquiring a multitude of skills, the ophthalmic nurse provides excellent care, is a vital part of the ophthalmology team, and decreases the stress of surgery for the patient. Understanding other mental and physical stresses affecting the patient help make surgery a more positive experience. PMID- 8509679 TI - Standards of ophthalmic clinical nursing practice. American Society of Ophthalmic Registered Nurses, Inc. (ASORN). PMID- 8509680 TI - Unusual corneal traumas. PMID- 8509682 TI - Everybody, somebody and nobody. PMID- 8509681 TI - Sexual harassment in nursing. PMID- 8509683 TI - A comparison of topical non-steroidal anti-inflammatory drugs to steroids for control of post cataract inflammation. AB - Fifty patients undergoing phacoemulsification with posterior chamber intraocular lens implantation were randomly assigned to receive either diclofenac sodium 0.1% eye drops (Voltaren Ophthalmic, CibaVision Ophthalmics, Duluth, GA) or prednisolone acetate 1.0% eye drops (Pred Forte, Allergan Pharmaceuticals, Irvine, CA) as their postoperative anti-inflammatory medication. The patients were examined one day, one week, and one month after surgery, and their postoperative inflammation was evaluated both by slit lamp assessment of cell and flare, and by objective measurement of cell and flare with the Kowa FC-1000 laser cell and flare meter. At each visit, the level of postoperative inflammation was the same for the two study groups. Thus diclofenac sodium was as effective an anti-inflammatory agent for postoperative inflammation as prednisolone acetate. PMID- 8509684 TI - Testimony before the Governor's Commission on Health Care Reform. PMID- 8509685 TI - Functional voiding disorders of childhood. AB - Voiding problems in children are common and lead to symptoms of incontinence, urinary tract infections, urinary frequency, and urgency. Most voiding disorders occur in children with relatively normal neurologic and urinary systems and are believed to be functional in nature. Functional voiding disorders have a complex etiology involving faulty decision making and toilet habits. These disorders present with various combinations of symptoms and may be difficult for the physician and the parents to recognize. A catalog of the most common voiding disorders and their treatment is outlined. The close relationship between voiding and stooling dysfunction and their treatment is also presented. PMID- 8509686 TI - Metastatic gastric cancer presenting as a pelvic mass. AB - Traditionally, the gynecologist is the primary physician involved in the assessment of an adnexal mass. History, physical examination, and radiologic evaluation often fail to reveal extrapelvic etiologies for an adnexal mass, especially in the premenopausal woman. Recently three premenopausal women with a pelvic mass referred to the gynecologic oncology service at the University of Kentucky were each found to have gastric carcinoma metastatic to the ovary. This paper discusses the clinical presentation of these women and the indications for the evaluation of the upper gastrointestinal tract in a patient with an adnexal mass. PMID- 8509687 TI - Clinical theophylline toxicity: acute and chronic. AB - Reliable methods for measuring serum theophylline levels have provided the clinician with a range of serum theophylline concentrations to maximize therapeutic results while minimizing potential adverse effects. Although serum theophylline levels are often quoted for diagnosing theophylline toxicity, intolerance of this agent is closely associated with clinical features that are more important than an absolute serum value. This report contrasts the two most common settings of theophylline toxicity and presents an approach to the treatment of each type. PMID- 8509688 TI - Learning in the real world. PMID- 8509689 TI - Hearing loss in diabetics. AB - The relationship between diabetes and sensorineural hearing loss has been disputed. This study compares 44 insulin-dependent diabetics with 38 age and sex matched controls. All had pure tone and speech audiometry performed, with any diabetic showing sensorineural deafness undergoing stapedial reflex decay tests. In 14 diabetics stapedial reflex tests showed no tone decay in any patient, but seven showed evidence of recruitment. Analysis of variance showed the diabetics to be significantly deafer than the control population. The hearing loss affected high frequencies in both sexes, but also low frequencies in the male. Speech discrimination scores showed no difference. Further analysis by sex showed the males to account for most of the differences. Analysis of the audiograms showed mostly a high tone loss. Finally duration of diabetes, insulin dosage and family history of diabetes were not found to have a significant effect on threshold. PMID- 8509690 TI - Severe radionecrosis of the temporal bone. AB - Severe radionecrosis of the temporal bone is a potentially lethal condition which still occurs despite improvements in radiotherapy. A series of seven such cases is presented to outline the varied clinical features and management of this disease. PMID- 8509691 TI - The use of antibiotic/steroid ear drops to reduce post-operative otorrhoea and blockage of ventilation tubes. A prospective study. AB - This prospective randomized study investigates whether the use of antibiotic/steroid ear drops (Betnesol-N) is effective in reducing early post operative otorrhoea and blockage of ventilation tubes (VTs). The study included 162 children who had bilateral VT insertion and used Betnesol-N ear drops in one ear only for three days after surgery, the other ear was left as control. These children were reviewed two weeks later and their ears were examined for VT patency, presence of blood or of mucopus. Statistical analysis of our results showed that the use of Betnesol-N ear drops has significantly reduced the incidence of post-operative otorrhoea within two weeks of VTs insertion (p < 0.01). However, these drops did not have a significant effect on the blockage rates of VTs with dried blood (p > 0.05). PMID- 8509692 TI - Grommets, swimming and otorrhoea--a review. AB - Ever since Armstrong reintroduced the concept of grommet insertion parents have been asking 'may my child swim?', yet there is still no consensus as to the correct answer. This paper reviews the work that has been done on this subject in the last 25 years. A review of the rates of otorrhoea following grommet insertion, irrespective of swimming, shows a variation from 12 to 64 per cent. Evidence suggests that pressures of 12-23 cm H2O are needed to push water through a grommet and that it is unlikely that water will enter the middle ear during surface swimming. Only bath water seems to cause significant inflammatory changes to middle ear mucosa. Not a single paper comparing swimmers with non-swimmers shows an increased rate of otorrhoea in those patients who swam; to the contrary, rates of otorrhoea were repeatedly higher in those patients who did not swim. The evidence suggests that swimming without ear protection can be safely permitted for children with grommets. PMID- 8509693 TI - Warfarin and epistaxis--a case controlled study. AB - Patients anticoagulated with warfarin form a small proportion of those admitted with epistaxis annually to ENT units. The authors formed the impression that such patients spend longer in hospital and have more complicated management than controls. A prospective age and sex matched controlled study of 20 consecutive patients admitted with epistaxis whilst anticoagulated was performed. This showed that these patients spent significantly longer in hospital than controls, with an additional expense in the study period of 10,500 pounds for inpatient bed nights alone. The management of these patients is more complicated and there is a subgroup of poorly controlled patients who present most of the problems. A potential solution is to improve community warfarin control and to involve general practitioners and haematologists in the re-establishment of warfarin following admission for epistaxis. PMID- 8509694 TI - The use of balloon catheters in the treatment of epistaxis. AB - Inflatable balloon catheters are widely used in the treatment of severe epistaxis and are designed to be filled either with air or liquid. A postal survey revealed that 87 per cent of respondents used an inflatant which was deemed inappropriate by the manufacturer. When balloons designed for water or saline were filled with air, they deflated rapidly, in some cases being virtually empty after 24 hours. Better and more accessible instruction leaflets are required if the balloons are to be used as intended. Foley catheters are frequently used as nasopharyngeal packs, in conjunction with anterior nasal packs. Paraffin in the commonly used anterior packs damages the rubber of the catheter, resulting in the balloon bursting. This should be recognized by clinicians as a possible cause of rebleeding. PMID- 8509695 TI - Combined therapy for carcinoma of the nasopharynx: a report of 49 cases. AB - From April, 1986 to June 1989, 49 patients (29 male, 20 female) aged 20 to 70 years old who developed carcinoma of nasopharynx (included 15 with relapses) were treated with neoadjuvant regional chemotherapy, followed by radiotherapy, or cryosurgery and radiotherapy. Thirty-three of the patients had squamous cell carcinoma with poor differentiation, four with well differentiated squamous cell carcinoma were included. Tumours were treated with three modalities: (1) Induction regional chemotherapy with temporal artery catheterization as well as superselective intra-arterial chemotherapy of the femoral artery (chemotherapeutic agents: pingyangmycinum (P), Cisplatin (D), Vincristine (V), Methotrexate (M) and P.D.M. programmes); (2) Liquid nitrogen cryosurgery in 25 cases; (3) Radiotherapy was carried out for two weeks after cryosurgery or immediately applied to those without cryosurgery after chemotherapy. The data showed CR (complete response--all tumour gone) and PR (partial response--more than 50 per cent reduction) in 40 cases (81.6 per cent) and NR (no response--less than 50 per cent or no response) in nine cases (18.3 per cent) following regional chemotherapy. All of the patients were followed up for more than one year, and 48 of them survived (97.9 per cent). Thirty-five cases were followed up over two years and 28 of them survived (80 per cent). Twenty cases were followed up over three years, and 12 of them survived (60 per cent). The effect of regional chemotherapy and cryosurgery in combined treatment for carcinoma of the nasopharynx is discussed in this paper. PMID- 8509696 TI - Are haematological tests warranted prior to tonsillectomy? AB - The use of phlebotomy for a full blood count (FBC) and group and serum storage (G&S) prior to tonsillectomy with or without adenoidectomy was assessed by means of a postal questionnaire sent to consultant otolaryngologists within the South West Thames region. This was compared with 'countrywide' practice assessed by means of questions to attenders at an otolaryngology course. A postal response rate of 86 per cent was obtained with 67 per cent within the region requesting a FBC prior to tonsillectomy and 50 per cent to adenoidectomy alone. This was much greater than for the 'countrywide' group with 24 per cent and 6 per cent respectively. Requests for pre-operative G&S were 17 per cent and 6 per cent respectively. This large difference in practice suggests that in the clinically healthy patient with no specific indications, pre-operative haematological investigations may be non-contributory, which has important financial implications. The maintenance of post-operative intravenous access is considered to be much safer, less traumatic and cheaper. PMID- 8509697 TI - The use of clostridium botulinum toxin in palatal myoclonus. A preliminary report. AB - Palatal myoclonus is a rare syndrome characterized by involuntary rhythmical movements of the soft palate giving rise to clicking objective tinnitus. The intrusive nature of the tinnitus prompts patients to seek medical advice but to date no single treatment modality has been shown to be consistently effective. We present three cases in whom various management regimens were unsuccessful and in whom botulinum toxin injection to the palatal muscles was undertaken. All three cases were rendered free of their tinnitus with complete abolition of the myoclonus. The questions of optimum dosage as well as frequency of injection will be answered as greater numbers are treated by this method. PMID- 8509698 TI - Larynx preservation after initial non-cisplatin containing combination chemotherapy plus radiotherapy, as opposed to surgical intervention with or without radiotherapy in previously untreated advanced head and neck cancer: final analysis after 12 years follow-up. AB - After a median follow-up of 12 years, median overall survival of 73 patients with advanced squamous cell carcinoma of the larynx was 65 months. The 61 per cent of patients responding to two courses of initial schedule A combination chemotherapy, not including cisplatin, and the 81 per cent of patients achieving a final complete remission after definitive local therapy, had median overall survival figures of 95 and 97 months respectively. Overall survival and relapse free survival in 51 patients treated with radiotherapy only with larynx preservation, were not significantly different from the 21 patients who completed their surgery with pre- or post-operative radiotherapy; median overall figures were 71 versus 65 months. These data add weight to our proposal that use of initial combination chemotherapy followed by radiotherapy may eliminate the need for radical surgery, so preserving the larynx in patients with advanced disease, and provides evidence of some long-term benefit with 32 per cent of this entire group surviving 12 years. PMID- 8509699 TI - Surgical decannulation of children with tracheostomy. AB - Over a five-year period during which 99 children underwent successful ward decannulation, 14 other children were deemed unsuitable and underwent surgical decannulation. The technique of surgical decannulation involves excision of the tracheostomy tract with any granuloma and splinting of the anterior tracheal wall by the use of an indwelling nasotracheal tube for 48 hours post-operatively. It is indicated in carefully selected patients whose tracheostomies are complicated by large suprastomal granulomas, anterior tracheal wall collapse or previous anterior rib graft collapse into the airway. Nine of the 14 decannulations were successful. Success is dependent upon accurate prior endoscopic assessment and satisfactory previous reconstruction surgery in cases of subglottic stenosis. The five failures (4.42 per cent of all decannulations) represent some of the most demanding airway problems encountered. PMID- 8509700 TI - Radiotherapeutic effect on oropharyngeal flora in patients with head and neck cancer. AB - The affect of radiotherapy on oropharyngeal bacterial flora was studied in the hope that this might help in controlling post-operative infections in previously irradiated patients. Eighty patients were included from whom swabs were taken before and at the end of irradiation, Swabs were also taken two weeks after treatment in the last 40 patients. Thirty healty controls were included. It was found that coagulase positive Staphylococcus aureus, beta-haemolytic streptococci, Candida albicans, B. proteus, and Pseudomonas aeruginosa, were significantly increased at the end of irradiation, while Klebsiella was increased significantly in the period after irradiation. Culture and sensitivity was performed for the organisms isolated in the last 40 patients. From this study it is evident that irradiation has a significant effect on oropharyngeal flora. PMID- 8509701 TI - Paraganglioma of the external auditory canal. AB - A rare case of paraganglioma of the external auditory canal is presented. It was treated by excision and no recurrence has been noted after 18 months of follow up. PMID- 8509702 TI - Unchanged unilateral hearing loss and ipsilateral growth of an acoustic neuroma from 1 to 4 cm. AB - Progressive sensorineural hearing loss is the most important early symptom of a cerebellopontine angle process. A case report is presented of a 42-year-old woman who was referred to our department in 1979. Oil cisternography showed non filling of the left internal acoustic canal. Audiometry was planned as the method of control, but she did not return until nine-years later. In 1988, an acoustic neurinoma of 4 cm diameter was found in the left CPA. Pure tone audiometry and speech audiometry showed that during the nine-year interval, her 60 dB flat sensorineural hearing loss and speech perception thresholds had remained almost unchanged. A follow-up with only tone and speech audiometry can lead to a false negative diagnosis in some of these cases. Calculation of the growth in tumour volume over nine years in this patient showed a tumour volume doubling time of about 15 months. PMID- 8509703 TI - Recovery from rhinocerebral mucormycosis in a ketoacidotic diabetic patient: a case report. AB - An 18-year-old woman with insulin-dependent diabetes mellitus developed an infection of the paranasal sinuses with Rhizopus oryzae resulting in facial swelling, hemiplegia and blindness of the right eye. The therapy of this rhinocerebral mucormycosis consisted of extensive surgical debridement, administration of high-dose amphotericin B, hyperbaric oxygen and control of the underlying predisposing diabetes mellitus. The patient eventually recovered with however, the loss of one eye. PMID- 8509704 TI - Fourth branchial arch anomaly: a rare incidental finding in an adult. AB - A rare finding of a fourth branchial arch anomaly discovered at laryngectomy is presented. Clinical and histological findings are documented. The incidence and presentation of fourth branchial arch anomalies is discussed. PMID- 8509705 TI - Intrusion of an incisor tooth into the contralateral frontal sinus following trauma. AB - Although intrusions of glass fragments into the frontal sinuses are not uncommon in traffic accidents, a case with a tooth in the frontal sinus has never been reported. We report a patient with traumatic inclusion of an incisor tooth in the contralateral frontal sinus. Radiographic investigations demonstrated the tooth in the frontal sinus though no skin damage was recognized on the upper face. The usefulness of CT scan in localizing the missing tooth after facial trauma and its route of entry into the contralateral frontal sinus is discussed. PMID- 8509706 TI - Osteomyelitis as a complication of a tracheo-oesophageal puncture. AB - Two cases of osteomyelitis of the cervical spine complicating tracheo-oesophageal puncture are reported. There was considerable delay between onset of symptoms and diagnosis in both cases due to pre-existing cervical arthritis. Previous radiotherapy was felt to be a contributory factor in both cases. PMID- 8509707 TI - The value of sonography in the management of cystic neck lesions. AB - Eight cases of cystic neck lesion of differing causes in whom sonography was carried out as part of investigation are described. These are thyroid cyst with haemorrhage, thyroglossal cyst, branchial cyst, cystic hygroma, parotid abscess of the neck secondary to malignant external otitis, cystic degeneration of a recurrent malignancy in the neck, sebaceous cyst and a cold abscess. They showed that sonography is better than clinical judgement in obtaining a diagnosis. Therefore, we recommend that ultrasound should be performed in all neck lesions prior to needle aspiration or open excisional biopsy. PMID- 8509708 TI - Solitary fibrous tumour: report of two new locations in the upper respiratory tract. AB - Solitary fibrous tumours are uncommon spindle cell neoplasms generally associated with serosal surfaces, especially the pleura ('localized fibrous mesothelioma'). Recently, these tumours have been documented in extraserosal sites. We report two solitary fibrous tumours, including one occurring in the paediatric age group, arising in two previously unreported locations, parapharyngeal space and epiglottis. These cases expand the range of sites where this tumour may originate and confirm the tendency of extrapleural cases to involve the upper respiratory tract and adjacent structures. PMID- 8509709 TI - Hibernoma in the parotid region. AB - Hibernoma is a benign tumour, arising from vestigial remnants of brown adipose cells, which have persisted from embryonic life. Although it is a well recognized entity, it is an extremely rare tumour. Recent reports estimate 81 cases in the world literature, only seven being in the neck. To our knowledge, it has never been reported in the parotid region. We report such a case and discuss the historical background of a hibernoma, along with its pathological and clinical behaviour. PMID- 8509710 TI - How to make the invisible anterior tympanomeatal angle visible. PMID- 8509711 TI - Evidence that cholesteryl ester and triglyceride accumulation in J774 macrophages induced by very low density lipoprotein subfractions occurs by different mechanisms. AB - The present investigations have examined the mechanism(s) whereby Sf 60-400 very low density lipoproteins (VLDL) from Type IV hypertriglyceridemic subjects cause cholesteryl ester and triglyceride accumulation in J774 macrophages. Both apolipoprotein (apo) E-poor and apoE-rich Type IV VLDL subfractions, isolated by heparin-Sepharose chromatography, were capable of enhancing cellular cholesterol and triglyceride content. The apoE-rich fraction was significantly more effective at inducing cholesterol esterification (P < 0.05) and accumulation of esterified cholesterol (P < 0.05), whereas both subfractions caused similar increases in cellular triglyceride content. Thus, the amount of VLDL-associated apoE determined the extent to which Type IV VLDL loaded J774 cells with cholesterol but not triglyceride. Two VLDL subfractions, Sf 60-400 and Sf 20-60, isolated from Type III subjects homozygous for apoE2, caused little or no effect on cellular esterified cholesterol content, whereas both fractions induced the same degree of cellular triglyceride accumulation as Type IV VLDL. Type IV VLDL induced cholesteryl ester accumulation was blocked by an anti-apoE monoclonal antibody, known to block the binding of apoE to the LDL receptor; however, the increase in cellular triglyceride was unaffected. Therefore, VLDL-induced triglyceride accumulation in this cell line can occur without apoE-mediated uptake of intact VLDL particles. The addition of heparin to J774 cells resulted in a 6-fold increase in lipoprotein lipase (LPL) activity in the media, and significantly enhanced the ability of Type IV VLDL to induce cellular triglyceride accumulation (P < 0.01), but significantly decreased cellular cholesteryl ester content (P < 0.025). Finally, Sf 60-400 VLDL from two subjects homozygous for apoC-II deficiency failed to increase cellular lipid content. However, the addition of exogenous apoC-II to C-II-deficient VLDL resulted in significant increases of both triglyceride and esterified cholesterol in J774 cells. In the presence of apoC-II, the anti-apoE monoclonal antibody blocked the cellular cholesteryl ester increase induced by C-II-deficient VLDL, but had no effect on the increase in cellular triglyceride. Collectively, these experiments demonstrate that extracellular lipolysis of Sf 60-400 VLDL by LPL is required for cholesteryl ester and triglyceride accumulation in J774 macrophages. After interaction with cellular LPL, VLDL triglycerides are hydrolyzed. The resulting free fatty acids are readily taken up by the macrophage, and re-esterified into triglyceride. Lipolysis proceeds until apoE epitopes are exposed, allowing the triglyceride-depleted remnant, containing all the cholesteryl ester, to be taken up via an apoE-mediated process. PMID- 8509712 TI - Regulation of sterol carrier protein-2 gene expression in rat liver and small intestine. AB - Sterol carrier protein-2 (SCP2) is a peroxisomal protein most highly expressed in non-steroidogenic tissues such as liver and small intestine. We have examined SCP2 gene expression during development and after alterations in lipid and bile acid metabolism and compensatory cell growth in the rat. The developmental expression of SCP2 displayed a biphasic pattern of relative mRNA abundance with a peak at day 19 to 20 of fetal life, reaching adult levels by day 14 and after day 14 in small intestine. In adult rats there was no effect on SCP2 mRNA abundance, or the relative proportions of the four SCP2 transcripts after gemfibrozil treatment, 30-fold changes in hepatic cholesteryl ester and triglyceride levels, bile ligation, compensatory hepatic or renal growth. However, immunoblot analysis of tissue homogenates revealed that SCP2 protein is decreased by 75% in the livers of gemfibrozil-treated animals and increased by 5-fold at 48 h in regenerating liver and in the remaining kidney after unilateral nephrectomy. Taken together these results suggest that SCP2 gene expression is developmentally regulated and modulated translationally or post-translationally in the adult rat by gemfibrozil and compensatory cell growth. PMID- 8509713 TI - Fluorescent derivatives of bile salts. III. Uptake of 7 beta-NBD-NCT into isolated hepatocytes by the transport systems for cholyltaurine. AB - Uptake of 7 beta-NBD-NCT ([N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-7 beta-amino-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2'-aminoethanesulfonate) in isolated rat liver hepatocytes occurs by saturable transport without being superimposed by simple diffusion. The dependency of flux rate of uptake on the concentration of 7 beta-NBD-NCT in the presence of Na+ (143 mM) and with Na+ depletion (1 mM) is best described by the assumption of two simple transport systems. Maximal flux rates of uptake Jn and half-saturation constants KT for 7 beta-NBD-NCT are in presence of Na+ for transport system 1 J1(Na+ 143) = 0.15 +/- 0.03 nmol/(min.mg protein) and KT1(Na+ 143) = 3.5 +/- 0.5 microM and for transport system 2 J2(Na+ 143) = 1.0 +/- 0.1 nmol/(min.mg protein) and KT2(Na+ 143) = 190 +/- 25 microM, and in case of Na+ depletion J1(Na+ 1) = 0.1 +/- 0.03 nmol/(min.mg protein), KT1(Na+ 1) = 3.0 +/- 0.5 microM, and J2(Na+ 1) = 0.85 +/- 0.9 nmol/(min.mg protein) and KT2(Na+ 1) = 195 +/- 27 microM. Uptake of 7 beta NBD-NCT by both transport systems is competitively inhibited by cholyltaurine in the presence of Na+ and with Na+ depletion. Two transport systems are likewise involved in the uptake of cholyltaurine in the presence of Na+ as well as in case of Na+ depletion. Their kinetic parameters are in presence of Na+ J'1(Na+ 143) = 1.55 +/- 0.14 nmol/(min.mg protein) and K'T1(Na+ 143) = 16.1 +/- 3.0 microM, and J'2(Na+ 143) = 0.51 +/- 0.05 nmol/(min.mg protein) and K'T2(Na+ 143) = 38.0 +/- 4.1 microM, and in case of Na+ depletion J'1(Na+ 1) = 0.10 +/- 0.02 nmol/(min.mg protein), K'T1(Na+ 1) = 7.7 +/- 1.2 microM, and J'2(Na+ 1) = 0.40 +/- 0.03 nmol/(min.mg protein) and K'T2(Na+ 1) = 41.0 +/- 4.2 microM. Uptake of cholyltaurine by both transport systems is competitively inhibited by 7 beta-NBD NCT in the presence of Na+ as well as in case of Na+ depletion. In both cases the inhibition constants are practically identical with the KT values for uptake of 7 beta-NBD-NCT. Photoaffinity labeling of isolated hepatocytes using 7,7-ACT (400 microM) resulted in the irreversible inhibition of uptake of both bile salts to similar extents, confirming the kinetic data that 7 beta-NBD-NCT is a true analogue of cholyltaurine. PMID- 8509714 TI - Molecular species of lecithins in human gallbladder bile. AB - Using a precise high performance liquid chromatography (HPLC) technique, we identified the molecular species of lecithins in gallbladder biles from patients with cholesterol gallstones (n = 29), pigment gallstones (n = 9), morbid obesity (n = 5), and "controls" (n = 10). The major lecithin species identified in all groups, in descending rank order as represented by the fatty acids in the sn-1 and sn-2 positions, were 16:0-18:2, 16:0-18:1, 16:0-20:4, 18:0-18:2, and 18:1 18:2. Lecithin species were found to be more numerous and in substantially different proportions than reported by previous investigators. No significant differences were found between any biliary lecithin species in the cholesterol and pigment stone groups. However, compared with controls, both cholesterol and pigment stone patients had smaller proportions of 16:0-20:4, the principal arachidonyl lecithin species. Using the HPLC elution sequence for quantifying the hydrophilic-hydrophobic balance, we developed a Hydrophobic Index for lecithin species in each bile based upon the principles proposed by D. M. Heuman for bile salt species. Hydrophobic indices of bile salts and lecithin were positively correlated (r = 0.48, R2 = 0.23, P = 0.0002) suggesting that more hydrophobic bile salts were associated with biliary secretion of more hydrophobic lecithins. The most hydrophobic major lecithin species, 18:0-18:2, was present in greater proportions in biles with cholesterol monohydrate crystals in their sediments and in those with cholesterol saturation indices greater than one. This work provides rigorous separation, identification, and quantitation of the lecithin species in human gallbladder bile from a large cohort of patients but, apart from a more hydrophobic bile salt pattern coupling more hydrophobic lecithins, we fail to identify any relationships of biomedical importance between lecithin species and other major biliary constituents. PMID- 8509715 TI - Dietary fish oil modification of cynomolgus monkey low density lipoproteins results in decreased binding and cholesteryl ester accumulation by cultured fibroblasts. AB - Dietary fish oil (FO) has been reported to increase low density lipoprotein (LDL) receptor function resulting in lower plasma LDL concentrations in the rat (Ventura et al. J. Clin. Invest. 84: 528-537, 1989). The purpose of this study was to determine whether dietary FO, as compared to lard, affected the receptor mediated uptake of LDL by cultured skin fibroblasts. Plasma LDL was isolated by combined ultracentrifugation and column chromatography from cynomolgus monkeys fed diets enriched in FO or lard and the effect of these two dietary fats on the binding of LDL and esterified cholesterol (EC) accumulation by cultured fibroblasts was determined. There was no difference in total plasma or LDL cholesterol concentrations between diet groups. The monkeys fed FO had significantly smaller LDL which, on average, contained less protein, phospholipid (PL), and free and esterified cholesterol compared to the LDL from monkeys fed the lard diet. FO LDL were less effective than lard LDL in competing for binding, internalization, and degradation of a standard 125I-labeled LDL by fibroblasts (11.0 +/- 2.4 vs. 3.0 +/- 0.8 micrograms LDL protein/ml for 50% displacement of binding, respectively; P = 0.013). FO versus lard LDL also resulted in less accumulation of cellular EC after a 24-h incubation with fibroblasts (7.7 +/- 0.2 vs. 13.0 +/- 0.4 micrograms EC/mg protein, respectively; P = 0.0001). In general, cellular EC accumulation was proportional to LDL particle size and LDL apoE/B molar ratio; however, LDL from the lard group resulted in greater EC accumulation even when LDL particle size and apoE content were nearly equivalent between diet groups. When LDL were isolated from the same animals by sequential ultracentrifugation, the lard LDL apoE was reduced 22% compared to column isolated LDL and this resulted in a 32% decrease in cellular EC accumulation. However, for FO LDL, apoE content was reduced 34% by sequential ultracentrifugation but this only resulted in a 10% decrease in EC accumulation. These results suggested that lard LDL contained more receptor-active apoE than FO LDL. We conclude that isocaloric substitution of fish oil for lard in the diet of cynomolgus monkeys results in LDL particles that bind less avidly to LDL receptors and in less EC accumulation in fibroblasts. The decreased binding of LDL from the FO group appears related to their decreased size and CE content as well as the decreased content of receptor-active apoE relative to the lard group. PMID- 8509716 TI - Decreased binding of apoA-I to phosphatidylcholine monolayers containing 22:6 n-3 in the sn-2 position. AB - Previous studies have shown that dietary fish oil can modify the distribution and fatty acyl composition of plasma phospholipids. Although it is known that the type of phospholipid can affect the binding of apolipoprotein A-I (apoA-I), little is known about the effect of n-3 fatty acid enrichment in phospholipids on apoA-I binding. We hypothesize that phosphatidylcholine (PC) surfaces containing n-3 fatty acids at the sn-2 position bind apoA-I less avidly than those containing sn-2 18:1. PC species containing sn-1 16:0 and sn-2 18:1 (POPC), sn-2 20:5 n-3 (PEPC), or sn-2 22:6 n-3 (PDPC) were used in apoA-I monolayer binding studies. The molecular surface area at any given surface pressure (tau) was ordered: PDPC > PEPC > POPC and at tau = 25 mN/m the molecular surface areas were 86.2, 78.8 and 72 A 2/molecule, respectively. Binding of [14C]apoA-I (radiolabeled by reductive methylation) to PDPC at tau i = 15 mN/m was less than that for POPC whether expressed as nmol A-I/m2 surface or molecules A-I/1000 PC. The apparent Kd for steady state apoA-I binding to PEPC (2.1 nM) and PDPC (2.2 nM) was greater than that for POPC (1.2 nM); the maximum binding capacity (nmol/m2) was ordered PEPC (9.4) > POPC (8.1) > PDPC (6.7). Similar results were found when a fixed amount of apoA-I was injected beneath the PC monolayers equilibrated at different initial surface pressures. The calculated surface area available for bound apoA-I was 15, 17, and 23 A 2/amino acid for POPC, PEPC, and PDPC at tau i = 15 mN/m, respectively. We conclude that the binding affinity of apoA-I for PDPC and PEPC is less than that for POPC and that apoA-I bound to PDPC is more loosely folded than that to POPC. These studies suggest that the type of sn-2 fatty acid can influence apoA-I binding to PC. PMID- 8509717 TI - Partial characterization of lipoproteins containing apo[a] in human atherosclerotic lesions. AB - Previously we quantified the amounts of immunoreactive apo[a] found in human atherosclerotic lesions extracted sequentially with phosphate-buffered saline (PBS) and guanidine hydrochloride (GuHCl). In this study we have attempted to characterize lipoproteins containing apo[a] in such PBS and GuHCl fractions, obtained from autopsy samples, in order to eventually determine their structure function relationships critical for evaluating the mechanisms that make them atherogenic. Apo[a] in the PBS extracts migrated slightly ahead of plasma Lp[a] on agarose electrophoresis. Although apo[a] in extracts showed the same isoforms as in plasma in SDS-PAGE, it was also highly fragmented. When a d < 1.10 g/ml ultracentrifugation fraction of the PBS extract was subjected to gel filtration, a major part of the immunoreactive apo[a] in this fraction co-isolated with plasma Lp[a]. When the Lp[a]-sized fraction was further separated by density gradient ultracentrifugation, a subpopulation was isolated containing apo[a] in the 1.06 < d < 1.08 g/ml density range that was free of lesion-derived low density lipoprotein (LDL) (A-LDL). This fraction contained immunoreactive apo[a] and apoB, had a total cholesterol to protein ratio of about 1, and demonstrated increases in fluorescence (360 ex/430 em) and conjugated dienes that were even greater than values obtained for the corresponding A-LDL sample. The void volume fraction following gel exclusion chromatography of the d < 1.10 g/ml fractions contained both apo[a] and apoB that comigrated on nondenaturing PAGE, suggesting that they were present on the same particle. Apo[a] in GuHCl extracts comigrated with plasma Lp[a] on agarose electrophoresis and contained apo[a] isoforms of similar molecular weights as those found in corresponding plasma samples. When the GuHCl extract was subjected directly to gel filtration in the presence of 6 M GuHCl, two included peaks of apo[a] immunoreactivity were present, one eluting slightly ahead of plasma Lp[a], the other slightly ahead of plasma LDL. Collectively, these data indicate that apo[a] is present in human atherosclerotic lesions in forms resembling intact but oxidized plasma Lp[a], as larger particles possibly representing Lp[a] complexed to itself or other plaque components, and as slightly smaller particles possibly representing degraded Lp[a]. PMID- 8509718 TI - Independent mutation of arginine(3500)-->glutamine associated with familial defective apolipoprotein B-100. AB - Familial defective apolipoprotein B-100 (FDB) is characterized by a decreased affinity of low density lipoprotein (LDL) to the LDL receptor resulting in a dominantly inherited increase of plasma LDL. It is postulated that FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apoB gene creating a substitution of glutamine for arginine in amino acid 3500. The arginine(3500)- >glutamine mutation has been identified on the same haplotype of the apoB gene in several populations from North America and Europe, suggesting that it occurred on a single ancestral gene. Independent mutations were not observed. The purpose of this paper is to report on a family where individuals show a dominantly inherited increase of plasma LDL associated with an independent arginine(3500)-->glutamine mutation as determined by haplotype analysis using polymorphic markers of the apoB gene. The identification of these individuals is strong evidence that the arginine(3500)-->glutamine mutation is causative for the defective binding of apoB-100. PMID- 8509719 TI - Hepatic production of very low density lipoprotein, catabolism of low density lipoprotein, biliary lipid secretion, and bile salt synthesis in rats fed a bean (Phaseolus vulgaris) diet. AB - Rats fed a bean diet develop a significant hypocholesterolemia. The catabolism of low density lipoprotein (LDL; d 1.019-1.063 g/ml) was studied in vivo and in vitro in the isolated perfused liver of rats fed either a casein or a bean diet. The clearance of LDL was significantly increased by 100% from 0.38 +/- 0.04 to 0.63 +/- 0.04 ml/h x 100 g body wt in vivo in the bean-fed rat. Similarly, the clearance of homologous and heterologous (human) LDL was also increased by 100% in the isolated perfused liver of bean-fed animals. Spleen, kidney, and hepatic cholesterogenesis was increased by 150% in these animals. Bile salt synthesis was increased from 1.54 +/- 0.02 to 2.84 +/- 0.09 nmol/min x g liver wt (P < 0.02) and biliary cholesterol output by 200% from 0.81 +/- 0.03 to 2.18 +/- 0.04 nmol/min x g (P < 0.02) in the isolated perfused liver of rats fed a bean diet. These results explained the depletion of hepatic cholesterol and were consistent with the LDL turnover studies, suggesting that apoB/E receptor activity was increased in these animals. ApoB and triglyceride secretion in the d < 1.060 g/ml lipoprotein fraction of liver perfusates remained normal in the bean-fed rats. In contrast, total sinusoidal cholesterol output isolated in the d < 1.060 g/ml fraction significantly decreased by 100% after 90 min of perfusion. Cholesterol output in the d > 1.060 g/ml lipoprotein fraction was unmodified by the bean diet. These data demonstrate that key metabolic pathways of hepatic cholesterol are modified in the bean-fed rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509720 TI - Effect of fish oil supplementation on the composition of molecular species of choline and ethanolamine glycerophospholipids in ruminant muscle. AB - Choline glycerophospholipids and ethanolamine glycerophospholipids of ruminant skeletal muscle contain approximately 40% and 65% plasmalogen, respectively. In the 1,2-diacyl-sn-glycero-3-phosphocholine (diacyl CPG), 16:0-18:2(n-6) and 16:0 18:1(n-9) accounted for about 50% of the total molecular species; in the 2-acyl 1(1-alkenyl)-sn-glycero-3-phosphocholine (alkenyl CPG), 16:0-18:2(n-6) was the predominant species. Fish oil supplementation resulted in a sixfold increase in the proportion of 16:0-20:5(n-3) and a two- to threefold increase in the proportion of 18:1-20:5(n-3) and 16:0-22:6(n-3) in the diacyl CPG, and there was a 40% decrease in the proportion of 16:0-18:1(n-9). In the alkenyl CPG, fish oil supplementation increased the proportion of molecular species containing C20 and C22 polyenoic fatty acids from 34% to 64%; in both sheep and cattle, the proportion of 16:0-20:5(n-3) was greater than any other molecular species. In contrast to the diacyl CPG, there was also an increase in the proportion of 18:0 20:5(n-3) in the alkenyl CPG. In the 1,2-diacyl-sn-glycero-3-phosphoethanolamine (diacyl EPG), 18:0-20:4(n-6) represented about 30% of the molecular species and this was reduced to less than 20% by fish oil supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509721 TI - Reverse-phase high-performance liquid chromatographic assay of phospholipases: application of spectrophotometric detection to rat phospholipase A2 isozymes. AB - This paper appraises an HPLC method for assaying phospholipase A2 (PLA2). The procedure is based on heptane-isopropanol-H2SO4 extraction of fatty acids released by the enzyme in the presence of margaric acid as an internal standard, and precolumn derivatization with 9-anthryldiazomethane. The derivatives of naturally occurring long-chain fatty acids were accurately determined by reverse phase HPLC with ultraviolet detection at 254 nm; the fatty acids were identical with margaric acid in terms of their extraction efficiency in the presence or absence of a bile salt, reactivity with the labeling reagent, and molar extinction coefficients of their derivatives. HPLC conditions were optimized so as to separate the derivatives of palmitic and oleic acids completely within 7 min. The use of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/cholate system as substrate proved useful for the sensitive detection of PLA2 activities in rat tissue homogenates. Distribution of immunoreactive pancreatic and group II phospholipases A2 was estimated from the degree of inhibition of enzyme activities by specific antibodies raised against either forms of phospholipase A2 isozymes. The results were consistent with those of immunoblot analyses. PMID- 8509722 TI - Adipose tissue cholesteryl ester transfer protein mRNA in response to probucol treatment: cholesterol and species dependence. AB - Probucol treatment results in an increase in plasma concentrations of cholesteryl ester transfer protein (CETP) which may account, in part, for the effects of this agent on plasma concentrations of HDL cholesterol. We have examined the mechanism by which probucol increases plasma CETP and have determined the associated changes in the plasma distribution of high density lipoprotein (HDL) particles. Studies were carried out in nine hypercholesterolemic subjects and five normal volunteers. Probucol treatment resulted in a 31% increase in plasma concentrations of CETP and a 23% decrease in HDL cholesterol (P < 0.01). The plasma concentration of LpA-I decreased by 40% (P < 0.01) whereas no change occurred in the LpA-I/A-II subclass of HDL. Plasma CETP increased significantly by 1 week of therapy and remained stable over 10 to 14 weeks of therapy. In spite of the significant increase in plasma concentrations of CETP, the abundance of CETP mRNA in peripheral adipose tissue decreased markedly (P < 0.001). These results suggested that probucol may alter CETP synthesis in another tissue such as liver or, alternatively, may have other effects on CETP secretion into or catabolism out of the plasma pool. Further studies were carried out in hamsters because, in this species, adipose tissue is a major site and liver is a negligible site for CETP synthesis. Hamsters were fed probucol with or without dietary cholesterol because this species was previously shown to respond to dietary cholesterol with an increase in adipose tissue mRNA levels and in plasma CETP concentrations, thus providing the opportunity to determine whether probucol would alter these parameters independently of the dietary cholesterol effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509724 TI - On the true numbers of uninsured Americans. PMID- 8509723 TI - Facilitated method for measurement of biliary secretion rates in healthy humans. AB - We have developed a facilitated method for determining secretion of constituents into bile. The ratio of constituent/bilirubin was measured in gallbladder bile and multiplied by bilirubin secretion rate, estimated by measuring endogenous production of carbon monoxide (VCO) by breath sampling. Accuracy of this method was assessed by measuring secretion rate of 99mTechnetium-labeled disofenin during steady-state constant intravenous infusion. In nine subjects, mean (+/- SEM) secretion of disofenin by the CO method was 104.2 +/- 7.2% of expected and by standard marker perfusion was 97.8 +/- 13.1% of expected. In ten subjects, secretion rate of cholesterol by the CO method averaged 103 mumol/h by the CO method compared to 113 by marker perfusion (NS). Compared to marker perfusion (which is believed to reflect 24-h secretion rate), the CO method significantly underestimated secretion rate of bile acid (1110 vs. 1332 mumol/h, P = 0.076) and lecithin (295 vs. 413 mumol/h, P = 0.01), probably because gallbladder bile contained a disproportionate amount of fasting versus postprandial bile. Thus, this new method provides an accurate secretion rate for biliary constituents secreted at a relatively constant rate, including cholesterol, with less variability than marker perfusion. However, it can be used to estimate secretion of bile acid and lecithin only when a 20-30% underestimation of 24-h secretion is acceptable. PMID- 8509725 TI - Readers offer suggestions for health care reform. PMID- 8509726 TI - Readers offer suggestions for health care reform. PMID- 8509727 TI - What are the implications of telemedicine on private practice in Georgia? PMID- 8509728 TI - Healing, to heeling, to heal-in, to get-real-in. PMID- 8509729 TI - Planning limits taxes in estate settlement. PMID- 8509730 TI - A guide to Georgia's new self-referral statute. PMID- 8509731 TI - Vertical integration: what does this "swing of the pendulum" hearld for you and your patients? PMID- 8509732 TI - Telemedicine: bringing medical care to isolated communities. PMID- 8509733 TI - Mobile intensive care units and their role in inter-hospital transfers. PMID- 8509734 TI - The significance of dysplasia in colorectal adenomatous polyps associated with carcinoma. AB - The relation of colorectal carcinoma and adenomatous polyps was studied retrospectively in 72 patients. Severe dysplasia was found in 47.8% and malignant transformation in 18.2% of the patients with adenomatous polyps and coincidental colorectal carcinoma. The incidence decreased to 21.4% and 7.1%, respectively, in patients with adenomatous polyps only. This difference between the two groups constitutes indirect evidence of malignant potential of adenomatous polyps associated with colorectal carcinoma. Moreover, when severe dysplasia of an adenomatous polyp is found, the patient should be carefully examined for synchronous colorectal carcinoma. PMID- 8509735 TI - Scanning electron microscopic observation of the vascular wall cells in human dental pulp. AB - The following six vascular segment types were identified in human dental pulp based on morphological differences in the periendothelial cells: (a) muscular arterioles with at least two compact layers of smooth muscle (SM) cells; (b) terminal arterioles with at least one compact muscle layer; (c) precapillary arterioles with an incomplete muscle layer; (d) capillaries with scattered pericytes; (e) postcapillary venules with clustered pericytes; and (f) muscular venules with at least one layer of flattened SM cells. In almost all muscular and terminal arterioles, the surface of SM cells showed marked to slight irregularities indicating vasoconstriction apparently caused by local administration of anesthetic containing epinephrine. Flattened SM cells in muscular venules also showed surface irregularities. SM cells in precapillary arterioles and pericytes in capillaries and most postcapillary venules, however, showed no distinct features of constriction. PMID- 8509736 TI - Sealing ability of three materials used to repair lateral root perforations. AB - Thirty-five extracted single-rooted human teeth were decoronalized, root filled with AH-26 and gutta-percha, and perforated at the apical one third level. Repairs of the lateral perforations were carried out with three materials: amalgam plus cavity varnish, EBA cement, and silver glass-ionomer cement. Negative controls were not perforated and positive controls had unrepaired perforations. The roots were then implanted subcutaneously in rats for 5 days to place the materials in a surgical environment. Following retrieval, the roots were placed in a solution containing 20 microCi/ml of calcium-45 for 7 days to measure microleakage. They were rinsed, sectioned, and autoradiographs of the repaired perforations were made. The autoradiographs were projected onto a screen and the extent of penetration of the radioisotope measured. Statistical analysis showed that the EBA cement group exhibited significantly less leakage than the silver glass-ionomer cement group (p < 0.05). No differences were found between the other groups. It was concluded that EBA cement provides a superior seal in lateral root perforations to silver glass-ionomer cement while amalgam was intermediate between the two. PMID- 8509737 TI - Accuracy of the Endex with variations in canal irrigants and foramen size. AB - Several electronic apex locators (EALs) are currently available. The manufacturer of a new device, the Endex, claims that it is accurate regardless of canal conditions. This study compared the accuracy of the Endex with that of the Exact a-pex, the Sono-Explorer Mark III, and the Neosono-D SE as to the effects of fluids in the canal and variation in foramen size. Sixty extracted single-canaled teeth were divided into two groups (narrow and wide foramina), depending on whether the apical foramina permitted the tip of a #30 K file to pass through. An in vitro model was used, in which teeth were fitted in test tubes with the roots immersed in 1% agar in phosphate-buffered saline. Root canal lengths were measured in dry canals, then with ethanol, Xylocaine, and sodium hypochlorite in the canals by each electronic apex locator. These lengths were compared with those of the actual root canal lengths. No significant differences were noted among the instruments in dry canals regardless of the foramen size. The endex was generally superior to the other instruments examined in canals containing conductive fluids, especially where the apical foramen was widened. PMID- 8509738 TI - Effect of sterilization on contaminated sponges. AB - Sponges are routinely used as a storage medium for endodontic files during clinical practice; however, very little research has been done to determine the effectiveness of sterilization procedures for these contaminated sponges. The purpose of this in vitro study was to determine the efficacy of chemical vapor sterilizers (chemiclaves), steam pressure sterilizers (autoclaves), and dry heat sterilizers on laboratory contaminated sponges. Four different types of sponges were used in this study: a black, relatively nonporous sponge; a red, semiporous stationary sponge; a blue, endodontic sponge, and a yellow, common household sponge. Natural sponges were eliminated from the study, because their large pore size made them unsuitable as a storage medium for endodontic instruments. The sponges were divided into three groups: chemiclave, autoclave, and dry heat. Five samples of each sponge type were impregnated with biological indicating strips containing spores of Bacillus stearothermophilus. Each sponge was subjected to 25 cycles of sterilization. The spore strip indicator was inserted into the sponges at 1, 5, 10, 15, 20, and 25 cycles. The spore strip was cultivated in trypticase soy broth medium solution at 55 +/- 1 degree C for 7 days. At 7 days the culture vials were read for turbidity; its presence indicating a positive culture. The samples that were subjected to chemiclaving demonstrated positive cultures of 0.00%, 0.00%, and 30.00% and those to autoclaving 3.33%, 0.00%, and 0.00% positive cultures for the black, red, and blue sponge types, respectively. None of the sponges survived dry heat sterilization. The O-Cell-O sponges become unusable when subjected to all of the sterilization methods used in this study. PMID- 8509739 TI - Experimental apical sealing with a new canal obturation system. AB - Twenty-seven root canals were obturated by the Thermafil system after conventional preparation. The lateral condensation technique was used as a control in 11 other canals. All specimens were immersed passively in India ink for 3 days at 37 degrees C. After rendering all roots transparent, no statistically significant differences (p < 0.4) were seen in apical leakage as determined stereomicroscopically. Like-wise, no relationship was noted between leakage and the last apical file size used to prepare and clean the canals. PMID- 8509740 TI - Effect of calcium hydroxide on bacterial lipopolysaccharide. AB - Apical periodontitis and its concomitant periapical osteolysis is caused by pulpal infection, and bacterial lipopolysaccharide (LPS) is known to play a major role in the bone resorption process. Little is known concerning the effect of root canal intervisit dressings on residual LPS in root canals after bacterial cell lysis. The purpose of this study was to evaluate the effects of calcium hydroxide on bacterial LPS. Free hydroxy fatty acids were quantified in samples of LPS treated with calcium hydroxide. Calcium hydroxide treatment of LPS was shown to release elevated quantities of hydroxy fatty acids. It was concluded that calcium hydroxide hydrolyzed the lipid moiety of bacterial LPS, resulting in the release of free hydroxy fatty acids. This result suggests that calcium hydroxide-mediated degradation of LPS may be an important reason for the beneficial effects obtained with calcium hydroxide use in clinical endodontics. PMID- 8509741 TI - An evaluation of the number of condenser insertions needed with warm lateral condensation of gutta-percha. AB - The purpose of this investigation was to determine the number of condenser insertions needed to obturate root canal systems using warm lateral condensation. Forty epoxide blocks with one major and five lateral canals placed at varying angles were used. The blocks received either one, three, five, or seven insertions of the warm instrument. The findings revealed gutta-percha and or sealer in every lateral canal. Cold compaction of the heated gutta-percha produced more material in the lateral canals than did the use of the heated condenser alone. The optimum number of condenser insertions depended upon the position of the lateral canal, the size of the canal, and the bulk of material being heated. The areas of the main canal with a smaller diameter required fewer insertions of the warm condenser to push the gutta-percha into the lateral canals located in those areas. PMID- 8509742 TI - An enzyme histochemical study of the behavior of rat bone cells during experimental apical periodontitis. AB - Bone alkaline and tartrate-resistant acid phosphatase activities were studied in paraffin sections obtained from experimentally induced periapical lesions of rats. These enzyme activities were demonstrated despite the use of high temperatures during embedding. In the formation phase, numerous osteoblasts and periodontal ligament cells showed strong alkaline phosphatase activity. On the other hand, a number of osteoclasts and preosteoclasts showed tartrate-resistant acid phosphatase activity in the activated resorption sites of periapical lesions. It is suggested that enzyme histochemical applications to paraffin sections are a useful means for clarifying the behavior of bone cells and that bone remodeling has occurred in the periapical lesions. PMID- 8509743 TI - Vertical root fractures in endodontically treated teeth: a clinical survey of 36 cases. AB - A clinical study was done on 36 original cases of vertical root fractures along with the data gathered from 32 cases published previously in the literature. Vertical root fractures most frequently occur in posterior teeth in patients between 45 and 60 yr of age. The average elapsed time between the endodontic treatment and the subsequent diagnosis of vertical fracture was found to be approximately 10 yr. The evidence and symptoms most often found are mild pain in the area of the fractured tooth often accompanied by swelling and fistula, along with a deep pocket in just one area of the attachment surrounding the tooth. The sign most often revealed by X-ray is a radiolucent periradicular band. PMID- 8509744 TI - Root resection of endodontically treated teeth by erbium: YAG laser radiation. AB - Root resection was performed on endodontically treated extracted human teeth exposed to pulsed erbium:YAG laser radiation at energy levels between 50 and 90 mJ/pulse in wet and dry fields. The lased surfaces were examined by optical and scanning electron microscopy. The smooth, clean resected root surfaces, devoid of charring (in wet fields), indicate that the erbium:YAG laser has a potential application in endodontic periapical procedures. In addition, researchers have shown that the zone of thermal damage and carbonization following erbium laser exposure on soft tissues and bone is appreciably less compared with other lasers, and therefore its use may result in improved healing and diminished postoperative discomfort. PMID- 8509745 TI - A two-rooted maxillary central incisor with a normal clinical crown. AB - Successful endodontic management of a two-rooted maxillary central incisor was reported. The postoperative radiograph showed two distinct canals. PMID- 8509746 TI - A safe technique for removal of provisionally cemented crowns. AB - A technique is presented for removing full-cast crowns and porcelain crowns that have been temporarily or provisionally cemented. A rubber dam retainer clamp with rubber dam attached is placed on the crown and clamped near its margins. Steiglitz forceps are used to apply pressure and leverage. The assembled unit is removed with the Steiglitz and safely removes the loosened crown from the mouth. PMID- 8509747 TI - Characterization of bone-resorbing activity in human periapical lesions. AB - Extracts of human periapical granulomas were tested for the presence of bone resorbing activity. All granulomas (10 of 10) contained low but significant levels of bone-resorbing activity, ranging from 2.1 to 4.9% treatment-% control/mg specific 45Ca release, as determined by the fetal rat long bone assay. Healthy periodontal ligament and dental pulp had no significant resorbing activity. In characterization studies, the resorbing activity in an extract pool was unaffected by the presence of polymyxin B, indicating an active moiety distinct from lipopolysaccharide. Resorbing activity was also unaffected by heating to 56 degrees C for 30 min, but was completely abolished by proteinase K treatment or heating to 70 degrees C, indicating that activity was largely protein mediated. Fast performance liquid chromatography gel filtration studies demonstrated that activity could be resolved to two major peaks, of M(r) 30,000 to 60,000 (I), and 15,000 to 20,000 (II), with a minor peak present at < 1,000 (III). Peak III was identified as prostaglandin E2 by radioimmunoassay. In inhibition studies, virtually all of the resorbing activity present was inhibited by anti-interleukin 1 beta (69%) and anti-tumor necrosis factor beta (66%) antisera, whereas anti-interleukin 1 alpha and antitumor necrosis factor alpha had no effect. Treatment with the cyclooxygenase inhibitor indomethacin also reduced activity by 74%. Taken together, these data demonstrate that most bone resorbing activity present in chronic human periapical lesions is attributable to the action of resorptive cytokines interleukin 1 beta and tumor necrosis factor beta, acting via both indomethacin-dependent and independent pathways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509748 TI - Adhesion of a resin composite to bleached and unbleached human enamel. AB - Cylinders of a visible light-cured microfil resin were formed on and bonded to the flattened enamel surface of 15 human hemisected premolar teeth which had previously been subjected to three different treatments: (a) immersion in 35% hydrogen peroxide (HP) for 60 min, (b) immersion in 35% HP for 60 min followed by storage in distilled water for 1 day prior to resin application, and (c) immersion in saline (S) for 60 min. Specimens were stored in distilled water at 37 degrees C for 7 days prior to shear bond strength testing. A total of 30 specimens were tested. Statistical analysis of the data indicated that there was a highly significant reduction in shear bond strength between HP- and saline treated specimens. Water storage of HP-treated specimens for 1 day prior to resin application appeared to restore the adhesiveness but not to a point that was statistically significant. Scanning electron microscopic examination of randomly selected, fractured test specimens indicated that the reduction in bond strength may be related to alterations in the ability of the resin to attach itself to the HP-treated surface and to possible effects of the HP on the resin itself. PMID- 8509749 TI - Inductive effect of native dentin on the dentinogenic potential of adult dog teeth. AB - Autogenous dentinal matrix was exposed to the pulp cells of adult dogs in order to determine whether the mature pulp cells possess the ability to differentiate into odontoblast-like cells as a direct response to known inductive influences. The pulps of molars, premolars, and canines of three dogs (2 to 4 yr old) were mechanically exposed through buccal class V cavities. Pieces of demineralized or native dentin and predentin were implanted in the pulp sites for periods of 2 to 6 wk. The reactions were analyzed by light microscopy. Induction of dentin formation was observed only after native dentin implantation; either as early response to exposure of predentinal surfaces or around mineralized dentin after 3 postoperative wk. Encapsulation by fibrous connective tissue or matrix degradation was seen around demineralized dentin implants. A characteristic enhancement of circumferential pulpal dentin deposition around the implantation site was demonstrated after native dentin exposure to light and scanning electron microscopic examination. These data indicate that specific inductive influences given by the native but not the acid-conditioned dentin, when it is exposed to the pulp environment of adult teeth, are able to direct differentiation of odontoblast-like cells and to enhance the biosynthetic activity of primary odontoblasts. PMID- 8509751 TI - Adaptation of thermafil components to canal walls. AB - The desired result of the Thermafil system is described as a centered carrier encased by gutta-percha in apposition to the canal walls. This study examined, in curved canals, the intracanal relationships of: (a) the metal carrier; (b) the surrounding gutta-percha; and (c) the sealer. Following the manufacturer's recommended techniques, 20 resin blocks that had canals prepared with conservative flaring were obturated. Cross-sections were made in the cervical, middle, and apical thirds and were evaluated with a stereomicroscope and scanning electron microscope to determine the location of the Thermafil components. In an additional 20 resin canal preparations obturated with the Thermafil system, the sealer was stained with dye to evaluate coating patterns. Then, these blocks were sectioned at the apex and examined under the stereomicroscope for adaptation at the apical extent of the preparation. In most preparations, the carrier abutted the canal wall in the cervical and middle sections but was usually surrounded by gutta-percha in the apical one third. The adaptation of components showed the most variability at the most apical extent of the preparation; complete encasement of the carrier did not occur in any specimen. Sealer distribution was variable throughout, usually being absent in the apical canal. PMID- 8509750 TI - Healing of induced periapical lesions in ferret canines. AB - A previous study showed that the ferret canine is an appropriate model for inducing periapical lesions. Ferret canines were used in this study to study changes in periapical lesions after root canal treatment (RCT). After periapical pathosis was induced in the maxillary and mandibular canines of six ferrets, RCT was performed on three of the four canines in each animal. Each ferret received periodic intraperitoneal injections of Procion red dye. Two animals were killed at each of 4, 8, and 12 wk after RCT. Apices and surrounding lesions were evaluated radiographically, histologically, and by fluorescent microscopy. Periapical radiolucencies increased in size during induction but showed no changes after RCT. Lesions in untreated teeth showed features of granulomatous inflammation, mainly the presence of macrophages and lymphocytes. After RCT, there was histological evidence of healing in the form of cementum deposition, increased vascularity, and increased fibroblastic and osteoblastic activity. Fluorescent staining showed cementum deposition of variable thickness in the treated specimens. PMID- 8509752 TI - Effect of smear layer removal on the diffusion of calcium hydroxide through radicular dentin. AB - Forty single-rooted teeth were sectioned transversely through the cementoenamel junction and instrumented to a size #50 K-Flex file at the working length by saline irrigation. Each root was placed in a dilution vial containing 10 ml of normal saline, and the pH and Ca2+ levels were recorded after 24 h. The roots in group 1 then received a final irrigation with 20 ml of normal saline. Group 2 received a final irrigation with 10 ml of 17% ethylenediaminetetraacetic acid followed by 10 ml of 5.25% NaOCl to remove the smear layer. Group 3 was irrigated in the same manner as group 2, but calcium hydroxide (CH) was placed into the root canal. Group 4 was irrigated with 20 ml of NaOCl, and CH was placed into the root canal. The pH and Ca2+ levels were recorded at 1, 3, 5, and 7 days. After 7 days a 3- x 3- x 1-mm external defect was created in the coronal one third of the root surface. The pH and Ca2+ levels were subsequently recorded at 1, 3, and 7 days. Groups 3 and 4 demonstrated significantly higher H+ and Ca2+ levels than did groups 1 and 2 three days after CH placement and at all subsequent intervals. Group 3 demonstrated significantly higher H+ and Ca2+ readings at some but not all intervals. The results demonstrated that CH diffuses from the root canal to the exterior surface of the root and that the removal of the smear layer may facilitate this diffusion. PMID- 8509753 TI - Comparison of root canal preparation using different automated devices and hand instrumentation. AB - The pre- and postinstrumentation degree of curvatures in curved mesial root canals of mandibular molars were compared after preparation with eight automated devices and hand instrumentation. The straightening of the root canal was measured before preparation and after preparation to size 25 and 35. Procedural mistakes such as loss of working length or file fractures were also recorded. Following preparation to ISO 25, only the Endoplaner and the Canal Finder system showed significantly more straightening than hand instrumentation. After preparation to ISO 35, the Endoplaner and the Intra-Endo 3-LDSY showed significantly more straightening than hand instrumentation. Mecasonic, Excalibur, and the Canal Finder system also straightened the root canal more than hand instruments, but the results did not differ significantly. The best results with only moderate straightening and few cases of loss of working length were obtained by the Endolift and Giromatic handpieces, which both were comparable to hand instrumentation. PMID- 8509754 TI - An evaluation of 4% prilocaine and 3% mepivacaine compared with 2% lidocaine (1:100,000 epinephrine) for inferior alveolar nerve block. AB - The purpose of this study was to measure the degree of anesthesia obtained with 4% prilocaine and 3% mepivacaine compared with 2% lidocaine (1:100,000 epinephrine) for inferior alveolar nerve block. Using a repeated measures design, 30 subjects randomly received an inferior alveolar injection using masked cartridges of each solution at three successive appointments. The first molar, first premolar, lateral incisor, and contralateral canine (control) were blindly tested with an Analytic Technology pulp tester at 3-min cycles for 50 min. Anesthetic success was defined as no subject response to the maximum output of the pulp tester (80 reading) within 16 min and maintenance of this reading for 50 min. Although subjects felt numb subjectively, anesthetic success as defined here occurred in 43 to 63% of the molars, in 53 to 67% of the premolars, and in 30 to 37% of the lateral incisors. No statistically significant differences in onset, success, or failure were found among the solutions. We conclude that the three preparations are equivalent for an inferior alveolar nerve block of 50-min duration. PMID- 8509756 TI - Incidence and possible causes of dental pain during simulated high altitude flights. AB - Of 11,617 personnel participating in simulated high altitude flights up to 43,000 feet, only 30 (0.26%) complained of toothache (barodontalgia). The cause of the barodontalgia in 28 episodes of pain in 25 of these subjects was investigated. Chronic pulpitis was suspected as the cause in 22 cases and maxillary sinusitis in 2. No pathosis was detected in the other four. In 10 cases in which the pulpitis was treated by root filling or replacing a deep filling, subsequent exposure to low pressure caused no pain. PMID- 8509755 TI - Periodontal tissue regeneration including cementogenesis adjacent to dentin bonded retrograde composite fillings in humans. AB - The roots of two incisors were treated by apicoectomy and a retrograde dentin bonded composite filling. Periapical healing was observed a few months later by radiography. Later, due to root fracture and marginal bone resorption, the apical parts were removed including adjacent periapical bone. A histological and scanning electron microscopic examination of the tissue showed reformation of periodontium adjacent to the composite, including reformation of a lamina dura, inserting Sharpey's fibers and cementum deposited in intimate contact with the composite. This finding is in agreement with previous observations of tissue surrounding retrograde dentin-bonded composite fillings placed in monkeys, indicating that tissue regeneration including cementogenesis may occur on composite material and consequently form a biological closure of the root canal. PMID- 8509757 TI - Nucleotide sequence and transcriptional analysis of the p10 gene of Spodoptera exigua nuclear polyhedrosis virus. AB - The p10 gene of Spodoptera exigua multiple nuclear polyhedrosis virus (SeMNPV) was localized on the XbaI fragment H (5.1 kb) of the physical map of the viral genome. The coding sequence of the SeMNPV p10 gene is 264 nucleotides (nt) long corresponding to a predicted protein of 88 amino acids with an MHF of 9607. The SeMNPV p10 protein showed only limited amino acid identity (39% and 26%, respectively) to those of Orgyia pseudotsugata MNPV (OpMNPV) and Autographa californica MNPV (AcMNPV) and thus appears less conserved than other viral proteins. The SeMNPV p10 gene was expressed by a transcript of approximately 450 nt, which started in the conserved baculovirus late gene promoter motif TAAG. The leader of the SeMNPV p10 transcript was AT-rich (92%) and at 36 nt was the shortest leader of all baculovirus major late genes reported so far. The SeMPNV p10 transcript terminated 6 nt downstream from a putative poly(A) signal sequence (AATAAA); the latter was 61 nt downstream of the translational stop codon TAA. Upstream and downstream of the p10 gene, partial putative ORFs were found that showed significant amino acid sequence identity to the baculovirus p26 and p74 proteins. It is concluded that the region of SeMNPV DNA containing the p10 gene is collinear with the corresponding regions in the AcMNPV and OpMNPV genomes. PMID- 8509758 TI - Simian immunodeficiency virus (SIVmac251) membrane lipid mixing with human CD4+ and CD4- cell lines in vitro does not necessarily result in internalization of the viral core proteins and productive infection. AB - The cell binding site of simian immunodeficiency virus (SIV) is believed to be the CD4 molecule. Several CD4+ cell lines are, however, resistant to infection by SIVmac251 in vitro and additional cell membrane molecules have been implicated in SIVmac251 entry. We investigated the binding, envelope fusion and entry of the viral core proteins (p27) of SIVmac251 into two human CD4+ cell lines (H9 and Sup T1) which are infectible, and one CD4+ (A3.01) and two CD4- cell lines (K562 and Raji) that are resistant to infection. The fusion of the viral and cellular membranes was monitored by a fluorescence assay for lipid mixing. Cell entry of the viral core was evaluated following virus-cell incubation and cell surface trypsinization. We found that SIVmac251 can bind to and fuse (membrane lipid mixing) in a temperature-dependent but pH-independent fashion with CD4+ and CD4- human-derived cell lines. In contrast, lipid mixing with CD4 expressing EL-4 mouse T cells or Mv-1-lu mink lung fibroblasts was absent or limited, suggesting that certain components of human cell membranes in addition to CD4 are involved in SIVmac envelope-cell fusion. Lipid mixing with the human cells was inhibited partially by soluble CD4. Anti-CD4 antibodies inhibited the lipid inter-mixing with H9, but not with Raji cells, whereas neutralizing anti-SIVmac sera inhibited fusion with both CD4+ and CD4- cells. Out of the five human cell lines tested, efficient entry of p27 and productive infection took place only with H9 and Sup T1 cells. In these two cases, the amounts of p27 internalized during virus-cell fusion correlated with the extent of infection. PMID- 8509759 TI - Analysis of the stimulation of reporter gene expression by the sigma 3 protein of reovirus in co-transfected cells. AB - The stimulation of reporter gene expression following co-transfection with the S4 gene of mammalian reoviruses was analysed. The sigma 3 protein of type 3 reovirus gave a five- to eightfold increase in expression of chloramphenicol acetyltransferase and beta-galactosidase but this was found to be dependent upon the nature of the promoter being used to drive reporter gene expression. The sigma 3 protein of reovirus type 1 failed to stimulate reporter gene expression under any of the conditions used. Hybrid constructs between the S4 genes of reoviruses type 1 and 3 were used to map the stimulation characteristic to the carboxy-terminal third of the gene. Analysis of the level of sigma 3 protein accumulation in transfected cells showed that the reovirus type 3 protein accumulated to a much higher level than that of reovirus type 1. Using the hybrid gene constructs this higher level of protein accumulation was shown to co segregate with the ability to stimulate reporter gene expression. PMID- 8509760 TI - Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding. AB - A surface glycoprotein (gp57/67) was previously shown to be involved in measles virus (MV) binding and characterized in our laboratory. Here, we described down regulation of cell surface gp57/67 after infection with MV. This effect is specific for MV since cells infected with canine distemper virus, closely related to MV, did not down-regulate gp57/67. The decrease in cell surface gp57/67 correlated with expression of MV glycoproteins and more particularly with the expression of MV haemagglutinin (MV-H). Indeed, expression of MV-H after infection with a vaccinia virus recombinant coding for MV-H was necessary and sufficient to induce down-regulation of gp57/67. Kinetics of cell surface expression of MV-H and gp57/67 showed that the degree of down-regulation was correlated with the amount of MV-H expressed by infected cells. Experiments using antibody-prelabelled gp57/67 and indirect immunofluorescence microscopy allowed us to follow the fate of gp57/67 and showed that down-regulation was occurring by rapid internalization of gp57/67 from the cell surface. These results provide additional evidence that the gp57/67 molecule is closely associated with the pathway of MV infection and also reveal a phenomenon which may be related to viral pathogenesis and persistence. PMID- 8509761 TI - Analysis of pathotype-specific structural features and cleavage activation of Newcastle disease virus membrane glycoproteins using antipeptide antibodies. AB - Peptides were synthesized, that correspond to cleaved and trimmed carboxyl termini of the F2 polypeptide regions of fusion (F) protein precursors (F0 proteins) in four different strains of Newcastle disease virus (NDV). These peptides differed only within the four carboxyl-terminal residues and represent F2 polypeptides of virulent (AV), low-virulence (EG) and avirulent (V4 and WA) pathotypes of NDV. Polyclonal rabbit antisera against each peptide reacted with their corresponding monomeric F2 polypeptides and F protein oligomers as analysed by immunoblotting of egg-propagated virions. Bidirectional cross-reactivity was observed between V4 and EG antisera and F2 polypeptides which differ only by a single variation of lysine and arginine at position 3 from their carboxyl termini. The other two antisera (AV and WA) were specific for their corresponding F2 polypeptides. All of these antisera were shown to react in a strain-specific manner with intact egg-propagated virions in an ELISA. A previously described antiserum, designed to target the haemagglutinin-neuraminidase (HN) protein precursor (HN0 protein) of avirulent strains of NDV, has been shown to be specific for residual HN0 protein of avirulent virions propagated in embryonated chicken eggs. Whereas the antiserum targeted at the carboxyl terminus of the V4 F2 polypeptide did not react with F0 proteins of cell culture-propagated strains in immunoblotting, antipeptide antibodies targeted at another region of the F2 polypeptide and a segment of the F1 polypeptide did react with the F0 protein from infected cells. These data are consistent with inclusion of the terminal carboxylate of the F2 polypeptides in the recognition determinants of the antibodies targeted at the carboxyl terminus of the V4 F2 polypeptide. The antisera described herein are ideally suited to rapid immunochemical pathotyping of NDV isolates and immunochemical characterization of the sites of intracellular cleavage activation of F0 and HN0 proteins and may be useful for defining interactions involved in F protein folding. PMID- 8509762 TI - Ambisense coding strategy of the rice stripe virus genome: in vitro translation studies. AB - Rice stripe virus (RSV), the type species of the tenuivirus group, contains four RNA segments as its genome. Sequence analyses of the three smaller segments indicated that all of them have ambisense coding strategies. To examine the ambisense nature of the genomic RNAs, we synthesized in vitro the RNAs carrying the putative open reading frames (ORFs) by transcribing cDNA clones for RNA segments 2, 3 and 4 in both directions using T7 RNA polymerase and translated each RNA in vitro using two systems: reticulocyte lysates and wheat-germ extracts. We detected the proteins encoded by the ORFs present in the 5'-proximal regions of both viral RNAs (vRNAs) and their complementary RNAs (cRNAs). Translation in vitro of total vRNA generated proteins encoded by the ORFs present in the 5' regions of vRNAs. The overall results are consistent with the prediction that RSV RNAs, at least up to segment 2, are ambisense in their coding strategy. PMID- 8509763 TI - Coat protein of cauliflower mosaic virus binds to ssDNA. AB - Alkali-denatured cauliflower mosaic virus (CaMV) virions incorporated ssDNA, added exogenously, into multimolecular complexes during dialysis against a neutral buffer. CaMV coat protein binding to tracer DNA, assessed by gel electrophoresis and autoradiography, was highly cooperative as judged by the absence of intermediate-sized complexes. The incorporation of labelled BglII fragments of a plasmid containing CaMV DNA into complexes was prevented by the presence of 0.16 g/l unlabelled calf thymus DNA. Lower concentrations of competitor DNA allowed binding of some BglII fragments although preventing the binding of others. The self-annealing poly(dI-dC) was much less efficient than calf thymus DNA in preventing the incorporation of fragments into complexes, suggesting a binding preference for ss- over dsDNA. In addition, dsDNA, minimally cross-linked to prevent strand separation, was bound only weakly. End-labelled ssDNA fragments in complexes were partially protected against DNase I. The nucleic acid-binding activity of CaMV coat protein may be responsible for the organization of replication complexes, the precursors to virion particles. PMID- 8509764 TI - Reduction of tobacco mosaic virus accumulation in transgenic plants producing non functional viral transport proteins. AB - Transgenic plants producing the 30K temperature-sensitive transport protein (TP) of tobacco mosaic virus (TMV) mutant Ni2519 (affecting cell-to-cell transport) were found to: (i) be susceptible to wild-type TMV U1 at 24 degrees C (a permissive temperature for Ni2519 TP), (ii) acquire a certain level of resistance to TMV U1 accumulation when maintained at 33 degrees C (a non-permissive temperature for Ni2519 TP) and (iii) lose the resistance to wild-type TMV after their transfer from 33 degrees C to 24 degrees C. It is suggested that reversible temperature-dependent conformational changes in Ni2519 TP are responsible for these phenomena and that production of a TP which is only partially functional in transgenic plants confers on these plants a resistance to the virus owing to reduction of the level of cell-to-cell transport. Transgenic tobacco plants producing the 32K TP of brome mosaic virus (BMV) acquired resistance to TMV U1 suggesting that BMV TP is partially functional in tobacco plants. PMID- 8509765 TI - The N-terminal protein of the polyprotein encoded by the potyvirus tobacco vein mottling virus is an RNA-binding protein. AB - The first predicted polypeptide encoded by the potyvirus tobacco vein mottling virus (TVMV) is a highly positively charged protein of predicted M(r) 29K that functions as a protease to perform the first predicted cleavage in the potyvirus polyprotein. We expressed this protein (P1pro) fused with glutathione S transferase (GST) and purified the fusion protein from engineered Escherichia coli. We found that the intact fusion protein, as well as samples in which the P1pro portion was liberated from GST by pretreatment with thrombin, was able to bind RNA. Binding activity was optimal at relatively high KCl concentrations, suggesting an interaction dependent on a specific protein structure and not just on the binding of the negatively charged phosphate backbone by the positively charged P1pro polypeptide. The TVMV P1pro preferred ssRNA over DNA or dsRNA, and showed a possible preference for sequences containing oligo(G) tracts. Like other potyvirus-encoded proteins, the TVMV P1pro therefore possesses more than one demonstrable biochemical activity and probably plays multiple roles in the TVMV life cycle. PMID- 8509766 TI - Encapsidation of a recombinant LuIII parvovirus genome by H1 virus and the fibrotropic or lymphotropic strains of minute virus of mice. AB - We previously constructed a recombinant LuIII parvovirus genome lacking viral coding sequences and used it to generate luciferase-transducing virions, by cotransfection of cells with a helper plasmid expressing LuIII viral proteins. Here, we describe similar cotransfections using alternative, replication defective helpers encoding the non-structural and capsid proteins of parvovirus H1, or of either the fibrotropic or lymphotropic parvovirus strain of minute virus of mice [MVM(p) or MVM(i)]. Each cotransfection generated transducing virus which directed luciferase expression after infection of HeLa cells. The transducing activity of virus produced using either LuIII or H1 helper plasmids could be specifically neutralized by antiserum raised against the corresponding infectious virus. When the recombinant LuIII parvovirus was pseudotyped with MVM(p) or MVM(i), the resulting virions efficiently expressed luciferase after infection in human or murine cells known to be permissive for both MVM strains. The MVM(p) pseudotyped virus also expressed this reporter efficiently when infected into the murine A9 fibroblast line. In contrast, the recombinant virus generated with an MVM(i) helper gave luciferase expression that was barely detectable after infection of A9 cells which are highly restrictive for MVM(i) productive infection. These results support the notion that the allotropic determinant of these MVM strains functions through their capsid proteins. Pseudotyping of recombinant parvovirus genomes should be useful in controlling their host range as vectors, and in studying mechanisms influencing the permissiveness of parvovirus infections. PMID- 8509767 TI - Molecular pathology of Alzheimer's disease. PMID- 8509768 TI - John Coakley Lettsom (1744-1815). PMID- 8509769 TI - The neuropathological necropsy and audit. PMID- 8509770 TI - The management of medical coma. PMID- 8509771 TI - The neurological founding fathers of the National Society for Epilepsy and of the Chalfont Centre for Epilepsy. AB - The National Society for Epilepsy is the largest epilepsy charity in the United Kingdom, and administers the Chalfont Centre for Epilepsy. The Society was founded in London in 1892 and its first task was to establish an agricultural colony where people with epilepsy could live and work; and this was the origin of the Chalfont Centre. Recently, details of the early history of the Society have come to light showing that neurologists from the National Hospital, Queen Square were instrumental in its foundation. The meeting in which the society was constituted was held in the house of Thomas Buzzard, chaired by David Ferrier, and its first resolution was proposed by John Hughlings-Jackson. Other neurologists associated with its early history include William Gowers, Victor Horsley, Howard Tooth, and W Aldren Turner. In this paper we review the society's history and the light it throws on the attitudes to epilepsy and neurology in London in this exciting late Victorian period. PMID- 8509772 TI - Dementia of frontal lobe type: neuropathology and immunohistochemistry. AB - Brains from 12 patients dying with a clinical diagnosis of frontal lobe dementia have been examined at post mortem. In pathological terms four groups were encountered. Groups A and B showed severe frontal and temporal lobe atrophy characterised histologically in group A by severe neuronal loss, spongiform change of the superficial laminae, and mild astrocytosis; in group B severe neuronal loss was accompanied by intense gliosis but with little or no spongiform change. Two patients in this latter group also showed inclusions in frontal cortex and hippocampus typical of "Pick bodies"; such patients were considered as having classic "Pick's disease". Group C patients showed severe striatal atrophy with variable cortical (frontal or temporal) involvement, with histological changes similar to patients in groups A and B. The single patient in group D showed mild frontotemporal atrophy with spongiform degeneration of the superficial laminae of the cortex and nigral damage, and was considered to have motor neuron disease with dementia. This study is consistent with previous reports showing that the clinical syndrome of frontal lobe dementia is pathologically heterogeneous. However, the nosological relationships within these pathological variants, and between them and conditions such as progressive aphasia were similar histopathological changes are present, remain uncertain. PMID- 8509773 TI - Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci. AB - Recent PET results indicate that the benzodiazepine (BZ) receptor density measured with the BZ receptor antagonist [11C]flumazenil is reduced in human epileptic foci. The present study examines the applicability of this finding in the presurgical investigation of patients with intractable partial epilepsy. In eight patients, the PET measurements were performed after injection of the BZ receptor antagonist [11C]flumazenil and [2-18F]2-deoxy-2-fluoro-D-glucose ([18F]FDG)--a tracer for measurements of the rate of regional glucose metabolism. The focus localising ability of the two PET tracers was examined using extra--and intracranial EEG recordings as reference. The focus was first determined visually on the PET images obtained after a bolus injection of each of the PET tracers. Its anatomical localisation and spatial delimitation was then evaluated for each patient with a computerised anatomical brain atlas. [11C]flumazenil was found to be a more sensitive and accurate focus localiser than [18F]FDG. This observation was valid both for quantified and non-quantified images. In the preoperative diagnosis of epileptic foci, the PET measurements of BZ receptors may be a suitable and, in some cases, superior method to the generally used "[18F]FDG-PET" method. PMID- 8509774 TI - A prospective study of patients with CT detected pallidal calcifications. AB - In a prospective study pallidal calcification was detected in 30 of 1478 (2%) adult patients, on CT brain scans. In 8 cases (26%), the calcifications were detected either years after, or during the course of, conditions known to cause basal ganglia calcification, including AIDS in four cases. Eight patients (three with AIDS) had disturbances of calcium and phosphorus metabolism. It was concluded that: a) pallidal calcification is not uncommon and aetiological factors may be recognised more often than previously reported; b) AIDS is emerging as a significant cause of pallidal calcification in young adults, and c) in AIDS and other conditions, abnormal calcium and phosphate metabolism may act in conjunction with local vascular changes. PMID- 8509775 TI - Symptomatic hyponatraemia: can myelinolysis be prevented by treatment? AB - The treatment of hyponatraemia is controversial because of the risk of causing central or extrapontine myelinolysis (EPM). Rapid correction with hypertonic saline to a low normal sodium level has its proponents; others feel that slow correction to below normal sodium values is preventative. Most investigators feel that overcorrection should be avoided. It is not known whether the magnitude of serum sodium change is more important than the actual rate of correction. We present three patients with hyponatraemia ranging from 103 to 105 mmol/l who were corrected slowly with normal saline, corrected quickly with hypertonic saline, or rapidly overcorrected with hypertonic saline. All became comatose and died; all had EPM with or without central pontine myelinolysis (CPM). The rate of correction, the solution used, or the magnitude of correction did not seem to protect against demyelination. In a review of 67 reported CPM cases since 1983, no patients documented as having CPM or EPM by radiological studies or necropsy were treated with water restriction only. A group of 27 hyponatraemic patients treated only with water restriction and 35 with diuretic cessation alone did not develop CPM or EPM. This may be a reasonable approach to patients with symptomatic hyponatraemia and normal renal function. PMID- 8509776 TI - Motor neuron disease and multiple sclerosis mortality in Australia, New Zealand and South Africa compared with England and Wales. AB - There has been a marked increase in the reported mortality from motor neuron disease (MND) but not multiple sclerosis (MS) in England and Wales and in a number of other countries. A comparison has been made of the mortality from MND and from MS for two time periods in Australia, New Zealand and South Africa. An increase in MND mortality occurred in Australia and New Zealand between 1968-77 and 1978-87, greater than that which occurred in England and Wales, but there was no increase in MS mortality. Among the white population of South Africa, the MND mortality was half of that in England and Wales, Australia and New Zealand in both time periods. Both MND and MS mortality is higher in the English-speaking than in the Afrikaans-speaking white South African-born. The marked increase in MND mortality which has now been reported from many countries, is good evidence that an environmental factor is important in causing this disease. The large differences in MND mortality in different populations may be important clues to the environment factors causing the disease. PMID- 8509777 TI - Konzo: a distinct disease entity with selective upper motor neuron damage. AB - Two Tanzanian patients with konzo were severely disabled by a non-progressive spastic paraparesis, since the sudden onset during an epidemic six years earlier. At the time of onset they had a high dietary intake of cyanide from exclusive consumption of insufficiently processed bitter cassava roots. MRI of brain and spinal cord were normal but motor evoked potentials on magnetic brain stimulation were absent, even in the only slightly affected upper limbs. Other neurophysiological investigations were largely normal but the more affected patient had central visual field defects. Konzo is a distinct disease entity with selective type upper motor neuron damage. PMID- 8509778 TI - Familial desminopathy: myopathy with accumulation of desmin-type intermediate filaments. AB - Two siblings developed cardiomyopathy several years before slowly progressive muscle weakness. Skeletal muscle biopsy specimens showed subsarcolemmal crescents of dark eosinophilic material in both type I and type II fibres. Immunohistochemically the subsarcolemmal material stained positively for the intermediate filament protein desmin and for the heat shock protein ubiquitin but for no other cytoskeletal proteins. Ultrastructurally the subsarcolemmal deposits consisted of aggregates of granular and filamentous material arising from Z bands. Follow up muscle biopsies six years later showed an increased number of the muscle fibres that contained subsarcolemmal aggregates that stained positively for desmin and ubiquitin. These clinical and pathological features characterise a rare familial myopathy associated with an unusual distribution of desmin intermediate filament proteins in skeletal and probably also cardiac muscle. PMID- 8509779 TI - Functional recovery in primates with brachial plexus injury after spinal cord implantation of avulsed ventral roots. AB - Intraspinal replantation of avulsed spinal nerve roots as a surgical treatment for motor deficits after severe brachial plexus injury was investigated in primates. Under general anaesthesia hemi-laminectomy was performed in cynomolgus monkeys (Macaca fascicularis). Ventral roots within the brachial plexus were then avulsed by traction and subsequently implanted into the ventrolateral aspect of the spinal cord. No dysfunction in the long fibre tracts was seen following surgery. Postoperatively there was a flaccid paralysis of the arm on the lesioned side. Severe atrophy developed within 5-7 weeks in the muscles supplied by the avulsed roots and EMG revealed denervation activity. Two to three months after surgery there were EMG signs of reinnervation, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and the animals' motor behaviour normalised. One year after surgery there was a full range of motion in the arm, but the EMG activity in the reinnervated muscles at maximal force was reduced. Tracing of regenerated motor neurons with horseradish peroxidase (HRP) injected into the biceps muscle revealed retrogradely labelled motor neurons confined to the ipsilateral ventral horn. It was concluded that intraspinal replantation of avulsed ventral roots in primates significantly promotes motor recovery in the muscles supplied by the lesioned spinal cord segments. PMID- 8509780 TI - High resolution SPECT with [99mTc]-d,l-HMPAO in normal pressure hydrocephalus before and after shunt operation. AB - Cranial CT and high resolution measurements of regional cerebral blood flow (rCBF) with brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethylpropyleneamine oxime ([99mTc]-d,l-HMPAO) were performed before and after shunt operation in 14 consecutive patients with dementia and normal pressure hydrocephalus (NPH). When compared with a control group of 14 age matched healthy volunteers, the group of NPH patients was characterised by an enlarged subcortical low-flow region, significantly reduced rCBF and enhanced side-to-side asymmetry of rCBF in the central white matter, and enhanced side-to side asymmetry in the inferior and mid-temporal cortex. Global CBF was normal. Shunt operation reduced the mean area of the ventricles on CT and of the subcortical low-flow region on SPECT. Global CBF was unchanged. All 14 patients had an abnormal pre-shunt rCBF pattern with enlargement of the subcortical low flow region, focal cortical blood flow deficits, or both. Shunt operation improved the clinical status in 11 patients, and the area of the subcortical low flow region correctly classified 3/3 unimproved and 10/11 improved patients. Shunt operation normalised or reduced the area of the subcortical low flow region in nine of 10 patients. It is concluded that SPECT with [99mTc]-d,l-HMPAO is a useful supplement in the diagnosis of NPH versus normal ageing, and that SPECT may help to identify patients not likely to benefit clinically from surgery. PMID- 8509781 TI - Crossed aphasia: a PET follow up study of two cases. AB - Two cases of aphasia after right hemispheric stroke in right handed patients are described. The first patient had a severe mixed transcortical aphasia, apraxia and neglect after a lesion involving the right lenticular nucleus and periventricular white matter; aphasia was still present after three months. The second patient had a mild, transient fluent aphasia after a small right hemispheric periventricular lesion. Studies with [18F]FDG and positron emission tomography (PET) showed functional depression extending to the structurally unaffected left hemisphere in both patients in the acute stage. After three months, in the patient with persistent aphasia, metabolism was still reduced in the right hemisphere, with some recovery of hypometabolism on the left, while metabolic values had returned to normal in the patient with full language recovery. A close parallelism between glucose metabolism and clinical course in crossed aphasia is shown, as well as the presence of a functional involvement of the structurally unaffected left hemisphere in the acute stage. PMID- 8509782 TI - Depression in acute and chronic aphasia: symptoms, pathoanatomical-clinical correlations and functional implications. AB - Depressive alterations were investigated in 21 acute and 21 chronic aphasic patients with single left sided strokes. The assessment of depression was based on a psychometrically evaluated German version of the Cornell Scale for Depression (CDS) and the Research Diagnostic Criteria (RDC). No significant difference was found concerning depression sum-scores between the two aphasic groups. The acute group, however, exhibited significantly higher ratings in items related to physical signs of depression and disturbances of cyclic functions. Patients corresponding to the RDC-syndrome of major depression were only found in the acute group. Neither age, sex nor degree of hemiparesis discriminated the patients on the severity of depressive symptoms. In the acute patient group, nonfluency of aphasia was the only parameter that could be identified which had an effect on the mood symptom scores. A CT scan analysis in the acute patient group showed an association between the severity of depression and anterior lesions. A significant correlation was found between CDS sum-scores and the proximity of the anterior border of the lesion to the frontal pole of the hemisphere whereas the volume of lesions seemed to have no effect on depressive alterations in acute aphasic patients. Superimposition of the lesions of the aphasic patients with major depressive disorders showed a common subcortical lesion area involving putaminal and external pallidal structures. PMID- 8509783 TI - Skeletal muscle bioenergetics in the chronic fatigue syndrome. AB - Skeletal muscle bioenergetics and control of intracellular pH have been investigated in 46 patients with chronic fatigue syndrome by phosphorus magnetic resonance spectroscopy. The results have been compared with those from healthy controls and from a group of patients with mitochondrial cytopathies affecting skeletal muscle. No consistent abnormalities of glycolysis, mitochondrial metabolism or pH regulation were identified in the group when taken as a whole, although in 12 of the 46 patients the relationship between pH and phosphocreatine utilisation during exercise fell outside the normal range. Of these, 6 patients showed increased acidification relative to phosphocreatine depletion while 6 showed reduced acidification. These findings do not support the hypothesis that any specific metabolic abnormality underlies fatigue in this syndrome although abnormalities may be present in a minority of patients. PMID- 8509784 TI - Analysis of neuropsychological functioning in patients with chronic fatigue syndrome. AB - Memory impairment dominates the cognitive complaints of patients with chronic fatigue syndrome (CFS). Twenty CFS patients were available for studies with a clinical and experimental battery composed of memory and cognitive tests. The results on objective testing indicated that the CFS patients had some mild memory impairment, but only on tasks requiring conceptually driven encoding and retrieval processes. There were no associations between the nature of the precipitating illness, self ratings of fatigue, physical findings, or laboratory determination and objective memory performance or self report of memory functioning. These generally negative results indicate that memory impairment in CFS patients is typically mild and involves memory processes that participate in conceptualising information. PMID- 8509785 TI - Mortality from Parkinson's disease in England and Wales 1921-89. AB - Mortality from Parkinson's disease in England and Wales was re-examined using published government statistics. The 300% increase in the crude mortality rate between 1921 and 1989 was largely attributable to the increase in the elderly population who suffer a higher prevalence of the disease. The dramatic fall in 1940 and rise in 1984 were artefacts caused by changes in certification. Age specific mortality fell after 1940 in all groups below 70 years and in both sexes, but increased in those over 75 years. Analysis by birth cohort showed a progressive decline in mortality at younger ages with successive cohorts but stable mortality in the elderly. Younger patients were probably misclassified cases of "late-onset" Parkinsonism following encephalitis lethargica who can be differentiated from older cases of idiopathic Parkinson's disease. Mortality decreased in all age groups in the 1970s but then increased in the early 1980s. This is comparable to trends in the United States and Scandinavia and suggests that the beneficial effects of levodopa delay death for several years. PMID- 8509787 TI - Late central demyelination after Fischer's syndrome: MRI studies. AB - The case of a patient who presented with clinical, electrophysiological, and MRI evidence of central demyelination is described. The patient had been admitted to hospital for Fischer's syndrome a few years previously. The association of these two events suggests that central and peripheral myelinopathy may be related in Fischer's syndrome. PMID- 8509786 TI - Transthyretin gene mutations in British and French patients with amyloid neuropathy. AB - Five patients, two British and three French, with late onset amyloid neuropathy were found to have mutations of the transthyretin (TTR) gene associated with the Portuguese and German types of familial amyloid polyneuropathy. Familial amyloid polyneuropathy is rare in the United Kingdom and has not previously been defined at a molecular genetic level. None of the patients had a history of affected antecedents; the role of TTR gene analysis in diagnosing known or suspected amyloid neuropathy, regardless of family history or ethnic background, is emphasised. PMID- 8509788 TI - Hypoglycaemic hemiplegia: a repeat SPECT study. AB - During a hypoglycaemic right hemiplegia induced by a deliberate overdose of oral hypoglycaemics, brain CT and angiography revealed no abnormalities. SPECTs made one day and six days later showed relative hypoperfusion in the left hemisphere. Repeat SPECT study suggested that the left hemisphere was more vulnerable than the right in the cerebral blood perfusion. This vulnerability might provoke the right hemiplegia in a critical condition, such as severe hypoglycaemia. PMID- 8509789 TI - Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis. AB - A 13 year old Greek girl with myasthenia gravis developed widespread muscle paralysis and atrophy after large parenteral doses of corticosteroids (5.48 g methylprednisolone). An electromyogram showed myopathy, creatine kinase concentration below normal, and a muscle biopsy showed severe myopathy with selective loss of the thick filaments (myosin). Previous reports of myopathy associated with large steroid doses have mostly been in patients who were also receiving non-depolarising neuromuscular blocking drugs. This patient is unique in that severe myopathy was associated with neuromuscular blockade caused by antibodies to acetylcholine receptors. The findings in this case suggest that high doses of parenteral corticosteroids in patients with myasthenia gravis may be dangerous and that blocking the neuromuscular junction with drugs or antibodies predisposes skeletal muscles to the injurious effects of corticosteroids. PMID- 8509790 TI - Optic neuritis and HIV-1 infection. AB - A patient is reported who developed acute optic neuritis in the context of severe immunodeficiency associated with HIV-1 infection. The clinical, laboratory, and radiological features are described and the possible associations with syphilis, multiple sclerosis, lymphoma, and HIV-1 infection are discussed. PMID- 8509791 TI - Achromatopsia in the aura of migraine. AB - A 49 year old woman reported an attack of transient neurological dysfunction associated with unilateral headache. A prominent feature of the aura was a period of complete achromatopsia, so that the visual scene was experienced in monochrome. The episode developed to include features of prosopagnosia and spatial agnosia before resolving completely. Other episodes of transient neurological dysfunction followed at regular intervals until prophylactic antimigrainous therapy was initiated. Four vessel cerebral angiography and MRI of the brain were normal. Possible causes of this unusual migrainous aura are discussed with reference to current concepts of cerebral localisation. PMID- 8509792 TI - Carbamazepine, serum thyroid hormones and myocardial function in epileptic patients. AB - Serum thyroid hormone and thyrotropin levels were assayed and the myocardial function was evaluated by measuring systolic time intervals both in 30 patients with epilepsy on long-term carbamazepine monotherapy and in 19 healthy volunteers. Serum thyroxine, free thyroxine and triiodothyronine levels were significantly lower (p < 0.001) in the patient group than in the control group and systolic time intervals were similar in both groups. PMID- 8509793 TI - Paraneoplastic cerebellar degeneration and limbic encephalitis in a patient with adenocarcinoma of the colon. AB - The rare association of two neurological paraneoplastic syndromes, paraneoplastic cerebellar degeneration and limbic encephalitis occurred in a 55 year old woman with a microscopic adenocarcinoma in a colonic polyp. Complete removal of the tumour by polypectomy brought about a favourable recovery from limbic encephalitis but the cerebellar ataxia remained. High titres of antineuronal nuclear antibody resembling anti-Hu were demonstrated in serum by immunohistochemistry using rat brain as a substrate. The antibody identified a protein band of 41 kDa on a Western immunoblot. PMID- 8509794 TI - Fatigue versus disengagement in unilateral neglect. AB - A letter cancellation task revealed neglect of the lower left quadrant when cancellation began at the top, but of the upper left quadrant when it began in the bottom. When the cancellation was done line by line through a "window" which covered all but the line currently worked on, the quadrant effects disappeared, so that fatigue could not explain these effects. An alternative hypothesis is that as the cancellation progressed, the subject's attention was attracted by progressively more stimuli on the right, and that disengagement difficulty and hence neglect increased proportionately to the number of stimuli. PMID- 8509795 TI - Progressive systemic sclerosis with CNS vasculitis and cyclosporin A therapy. PMID- 8509796 TI - Ocular myasthenia: diagnostic value of single fibre EMG in the orbicularis oculi muscle. PMID- 8509797 TI - Soluble interleukin-2 receptor levels in serum of patients with demyelinating polyneuropathy associated with monoclonal gammopathy. PMID- 8509798 TI - CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. AB - Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value. PMID- 8509799 TI - Reply to the letter by Weller (J. Neurol. Sci., 110 (1992) pages 232-233) PMID- 8509800 TI - Serum cortisol and outcome of ischemic brain infarction. AB - The predictive value of serum cortisol level on the prognosis in acute brain infarction of the carotid circulation territory was studied in 101 patients younger than 70 years. The levels of 7 a.m. and 7 p.m. serum cortisol were measured initially and at 1 week. All patients underwent a computed cerebral tomography (CT) within 2 days of the onset of symptoms, and a second CT 3 weeks or 3 month later. Serum cortisol values predicted the stroke outcome. Both the 7 a.m. and the 7 p.m. values in the initial and 1-week samples correlated positively with the severity of hemiparesis on the corresponding days. The 7 p.m. values predicted better than the 7 a.m. values the functional outcome and case fatality during the 3 month follow-up. Initially and at 1 week, the median 7 p.m. serum cortisol values were statistically significantly higher in those with frontally extending infarcts than in those with non-frontal infarcts. Both 7 a.m. fasting blood glucose and glycosylated hemoglobin (HbA1c) measurements were taken within 3 days of the onset in 95 cases. The patients were diagnosed to have prestroke normoglycemia (n = 73) and hyperglycemia (n = 22) on the basis of the HbA1c level. A highly significant (P = 0.0001) correlation was demonstrated between the initial 7 p.m. cortisol and 7 a.m. fasting blood glucose values in those with prestroke normoglycemia, suggesting that hyperglycemia during the acute phase of stroke is a stress response. PMID- 8509801 TI - Epidemiology of idiopathic intracranial hypertension: a prospective and case control study. AB - An epidemiologic survey of idiopathic intracranial hypertension (IIH) in Benghazi, Libya, over a period from September 1982 through August 1989 ascertained 81 patients. The group was comprised of 76 females and 5 males. Ages ranged from 8 to 55 years; the mean +/- S.D. was 28.6 +/- 7.9 for women and 21.0 +/- 14.5 for men. The average crude annual incidence rates for IIH per 100,000 persons were 2.2 for the total and 4.3 for females for all ages (3.2 for the total and 5.9 for the females when adjusted to the 1980 United States population). In females aged 15-44 years, IIH occurred at a rate of 12.0 per 100,000 per year; for those defined as obese, the rate rose to 21.4. Moderate to severe visual loss occurred as a sequelae in 20% of our patients. The extent of visual loss did not correlate with age at diagnosis, duration of symptoms, degree of obesity, use of oral contraceptive pills, cerebrospinal fluid (CSF) opening pressure, steroid treatment, or recurrence. We found no correlation between CSF protein and opening pressure. We conducted a case-control study on 40 consecutive female incident IIH patients and 80 age-matched female control subjects. Obesity and recent weight gain occurred more frequently in patients. More patients were married and more had irregular menses. The incidence rate for IIH described in our study is three to four times higher than that reported from the United States. PMID- 8509802 TI - Identification of central sulcus by using somatosensory evoked magnetic fields and brain surface MR images: three dimensional projection analysis. AB - We present a novel non-invasive technique for identification of the central sulcus on the brain surface by using three-dimensional magnetic resonance imaging (3D-MRI) in combination with somatosensory evoked magnetic fields (SEFs). The central sulcus was supposed anatomically on the brain surface by using 3D-MRI. On the other hand, the primary somatosensory area is determined by using SEF data with median nerve stimulation. Superimposition of the SEFs of the 25 ms response onto the brain surface MR images clearly demonstrated the dipole source located in the gyral fold just behind the supposed central sulcus in all subjects analyzed. Three-dimensional reconstruction of the brain surface image data facilitated visualizing the precise anatomical localization of the magnetic field activities from any angle and measuring the distance from the source to any point of interest. The potential clinical application of this technique is discussed. PMID- 8509803 TI - Flunarizine enhances rat retinal ganglion cell survival after axotomy. AB - After axotomy most central nervous neurons including retinal ganglion cells (RGCs) die in a few weeks, although their somata are not injured. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors or due to a calcium overload after excessive release of excitatory amino acids from dying cells. Flunarizine, as a potent blocker of voltage dependent Ca2+ channels and in higher concentration being an inhibitor of the Ca2+/calmodulin-dependent protein kinase II, is able to mimic the neurotrophic effect of NGF on dorsal root ganglion (DRG) neurons. To examine its neuroprotective value in the central nervous system (CNS), flunarizine (5 mg/kg body weight) was given daily to rats after unilateral axotomy of the optic nerve. The density of retrogradely labelled retinal ganglion cells (RGCs) was determined 14 days after axotomy. It could be demonstrated that flunarizine significantly enhanced RGC survival after axotomy in adult rats (P < 0.001; 1065 +/- 142 vs. 922 +/- 237 RGCs/mm2). PMID- 8509804 TI - Occurrence of primary biliary cirrhosis, CREST syndrome and Sjogren's syndrome in a patient with HTLV-I-associated myelopathy. AB - We report the occurrence of three autoimmune diseases (primary biliary cirrhosis, CREST syndrome and Sjogren's syndrome) in a patient with HTLV-I-associated myelopathy (HAM). The patient had the depressed cell-mediated immune responses but the infiltration of CD8-T cells was found in the cerebrospinal fluid and liver. The clinical and immunological features of this case are similar to those of chronic graft-versus-host disease. PMID- 8509805 TI - Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: as assessed by serial computed tomography and magnetic resonance imaging. AB - The present paper concerns serial examinations of computed tomography (CT) and magnetic resonance imaging (MRI) in 22 patients with sporadic amyotrophic lateral sclerosis (ALS). Supranuclear ophthalmoplegia developed in 13 and dementia in 3 patients. The investigations showed gradually progressive atrophy, first in the frontal and anterior temporal lobes then in the precentral gyrus, and later in the postcentral gyrus, anterior part of the cingulate gyrus, corpus callosum and brain stem tegmentum. MRI revealed high intensity signals on T2-weighted images in the precentral and adjacent gyri, frontotemporal white matter and pyramidal tract as well as rarely in the globus pallidus and thalamus. These neuroradiological changes were not related to the duration of the clinical course or to the degree of the motor impairment. These alterations may play a critical role in the supranuclear ophthalmoplegia seen in ALS patients. The dementia of ALS probably reflects involvement of both the frontotemporal lobes and limbic system. PMID- 8509806 TI - Notexin-induced muscle injury in the dog. AB - Notexin, a myotoxic phospholipase, was used to induce focal necrosis in the sartorius muscles of normal mixed-breed adult dogs and in 12-week-old beagles. Notexin injury caused pathologic changes similar to those of Duchenne muscular dystrophy (DMD) and its canine homologue, golden retriever muscular dystrophy (GRMD). All three conditions are characterized by increased serum creatine kinase (CK) levels, sarcolemmal defects, delta lesions, hyaline degeneration of myofibers, calcium-positive myofibers, and minimal effects on neurovascular structures. Four and 24 h after exposure to notexin, serum CK levels were elevated, and many myofibers were necrotic. In addition, by 24 h the necrotic areas were heavily invaded by mononuclear cells, and calcium-positive myofibers were prominent. Capillaries appeared intact even in areas of marked myonecrosis. Massive cellular infiltrate and myotube formation was evident at 3 days post injury. By 7 days, most affected fascicles were occupied by small immature myofibers. Regeneration was largely complete at 21 days. Our results suggest that notexin-induced muscle injury in dogs will be useful in the evaluation of potential therapies for DMD such as myoblast transplantation. PMID- 8509807 TI - Muscular ultrasound in idiopathic inflammatory myopathies of adults. AB - To evaluate the value of myosonography in inflammatory myopathies ultrasound of skeletal muscles was performed in 70 patients, aged 21-82 years, suffering from histologically proven polymyositis (n = 30), dermatomyositis (n = 18), granulomatous myositis (n = 9), inclusion body myositis (n = 13), and in 102 control persons. The sensitivity of muscle ultrasound in detecting histopathologically proven disease (82.9%) was not significantly different from electromyography (92.4%) or serum creatine kinase activity (68.7%). The positive predictive value of ultrasound was 95.1%, the negative predictive value 89.2%, and the accuracy 91.3%. The different types of inflammatory myopathies presented with typical, but not specific ultrasound features. Polymyositis showed atrophy and increased echointensity predominantly of lower extremity muscles, whereas in dermatomyositis clear muscle atrophy was rare and echointensities were highest in forearm muscles. Echointensities were lower in dermatomyositis compared to poly- and granulomatous myositis. Granulomatous myositis was characterized by the highest echointensities and a tendency towards muscle hypertrophy. Severe muscle atrophy was the most impressive feature in the majority of patients with inclusion body myositis. Comparison of ultrasound and histopathological findings indicates that muscle lipomatosis has a much greater impact on muscular echointensity than does muscle fibrosis. Ultrasound of myositis improved clinical assessment of patients by supplying differential diagnostic clues based on precise muscle size measurements and identification of mesenchymal abnormalities, particularly muscle lipomatosis. PMID- 8509808 TI - Neonatal undernutrition and short term administration of hydrocortisone and thyroxine: effects on rat brain hydrolases. AB - Brain enzymes activities that are likely to be involved in the catabolism of gangliosides were determined in controls (20% casein diet), postnatally undernourished (6.5% casein diet) and undernourished rats treated with either thyroxine or hydrocortisone, at 21 days of age. Postnatal undernutrition imposed by maternal protein deficiency during lactation resulted in a decrease in body weight and brain wet weight of the pups at 21 days of age. Administration of thyroxine or hydrocortisone to the undernourished pups every day between 16 and 21 days caused a further decrease in the body weight of the pups. On the other hand, the wet weight of brain showed a slight gain following hydrocortisone treatment. Postnatal undernutrition during lactation elevated the activities of beta-glucosidase, beta-galactosidase, beta-hexosaminidase and sialidase in rat brain. Short-term administration of thyroxine or hydrocortisone to the undernourished pups, every day between 16 and 21 days postnatal age decreased the enzyme activities. However, reversal of the increased enzyme activities to the normal lower level was completed only in the case of undernourished pups treated with hydrocortisone. PMID- 8509809 TI - Thyrotoxic atrial fibrillation: pathophysiology, detection, and management. AB - Hyperthyroidism is a frequently misdiagnosed cause of atrial fibrillation. Difficulties associated with diagnosis are related to physiologic idiosyncrasies, concomitant illnesses, and medication regimens that may alter thyroid function and thyroid function tests. These factors are described. Nurses have a key role in assisting patients to manage hyperthyroidism and atrial fibrillation through case finding, assessment, education, and psychological support. PMID- 8509810 TI - Radiofrequency catheter ablation of supraventricular tachycardias: clinical consideration and nursing care. AB - Radiofrequency catheter ablation is rapidly gaining acceptance as the treatment of choice for many types of symptomatic supraventricular tachycardia (SVT). Introduced in humans in 1987, the procedure has been met with enthusiasm because of its relative safety and high success rate in curing SVT. The typical patient with SVT can be both diagnosed and cured during the same electrophysiology study (EPS). Complications are few, with the majority of patients discharged in less than 48 hours. Nursing care centers on pre- and postprocedural teaching, assessing the effects of radiofrequency energy and implementing nursing orders to prevent postablation complications. PMID- 8509811 TI - A follow-up study of patients with implantable cardioverter defibrillators. AB - This study involves 381 patients who received an implantable cardioverter defibrillator (ICD) for management of serious ventricular dysrhythmias and were followed for up to 9 years. The device was effective in preventing sudden cardiac death (SCD), with survival rates of 97% at 3 years and 94% at 5 years. Complication rates were low. Two hundred and twenty-five patients received at least one shock; 2.3 shocks per patient year were received. Shocks were categorized as appropriate, indeterminate, or inappropriate. Definitions of these categories and their occurrence are discussed and the characteristics and experiences of these patients are described. PMID- 8509812 TI - Physiologic responses of coronary care patients to visiting. AB - The authors examined physiologic changes in myocardial infarction patients during a family visit in the cardiac intensive care unit (CICU) and the relationship of these changes to illness variables, patient preference for visits, and patients' perceptions of the supportiveness of the visit. Forty-eight patients were studied for changes in heart rate, blood pressure, ST segment, and oxygen saturation. Patients who had the greatest physiologic changes were among those who had had more severe infarcts. However, many patients in the severe category did not show such changes. Examination of the reactive group revealed that, in addition to having more severe infarcts, it included a greater percentage of smokers than did the nonreactive group. Visit preferences were relatively low, but as visit preferences increased, so did cardiovascular changes. Supportiveness scores were quite high, and these were positively correlated with cardiovascular changes. Clinical and research implications are discussed. PMID- 8509813 TI - Death of a support group member: a practical guide to helping other members cope. AB - Dealing with the death of a group member can have many important therapeutic benefits for both patients and family members. The bereaved family can benefit from the opportunity to "let go" of the support group and say good-bye to friends who shared a common problem. This article offers a practical guide for helping implantable cardioverter defibrillator (ICD) support group members cope with the death of a group member. The elements of grief work, so-called "curative" factors, and suggestions for leader protocols following death loss of a support group member are discussed. PMID- 8509814 TI - Diagnosing and treating ventricular tachycardia. AB - The misdiagnosis of wide complex tachycardias often leads to improper treatment and adverse patient outcomes. This article presents a thorough review of the validated electrocardiographic criteria useful in the diagnosis of ventricular tachycardia versus supraventricular tachycardia with aberrancy. Current information on bedside monitoring, pharmacologic and nonpharmacologic treatment, psychological impact, and discharge planning is discussed. PMID- 8509815 TI - Research connections: nursing practice and ECG monitoring. AB - This article reviews and critiques the study by Drew et al that describes the electrocardiographic monitoring practices of critical care nurses. The study was conducted with a national sample and documented standards of practice. The implications for practice, education, and research are addressed. PMID- 8509816 TI - Immune adjuvants for chemotherapy or radiotherapy in the 9L rat brain tumor model. AB - The therapeutic efficacy and toxicity of three biological response modifiers, Corynebacterium parvum (Cp), Chinese blister beetle extract (CBBE), recombinant human IL-1 alpha (rhIL-1 alpha), used alone or in combination with chemotherapy or radiotherapy, were investigated in the intracerebral (ic) rat 9L brain tumor model. Used alone, Cp (2 mg/rat, ip plus 70 micrograms/rat, ic), CBBE (5 microliters of an ethanol extract, ic), or IL-1 alpha (1 microgram/rat, ic or 1 microgram/rat x 3, q 3 d, ic), had no effect on animal survival compared to the untreated or saline treated controls. When combined with chemotherapy or radiotherapy, the three immunotherapeutic agents did not show any additive effects on survival compared to that observed with systemic BCNU (12 mg/kg), local ic bleomycin (0.25 unit), or local radiotherapy (16 Gy). While ic IL-1 alpha did not produce evident toxicity, there was fatal toxicity caused by ic Cp or CBBE treatment in a few animals. The combination of Cp and bleomycin produced severe neurotoxicity, resulting in the early death of animals. This study demonstrates a lack of efficacy of the nonspecific immune adjuvants IL-1 alpha, Cp or CBBE, used either alone or combined with cytotoxic chemotherapy or radiotherapy, in this rat brain tumor model. PMID- 8509817 TI - Intracranial ependymoma long term outcome, patterns of failure. AB - We analyzed 31 patients with intracranial ependymoma, all verified by secondary neuropathology review. There were 12 patients with ependymomas and 19 patients with anaplastic ependymoma by the WHO classification. Eight patients received craniospinal irradiation, 22 patients received cranial irradiation alone, and one patient was treated with chemotherapy alone. The median follow-up time was 11 years. The 5- and 10-year progression-free survivals (PFS) were 60% and 48%. Those with anaplastic tumors had a decreased 10 year PFS over those with low grade lesions: 26% vs. 55% (p = 0.02). Delivering spinal irradiation in addition to cranial irradiation did not improve outcome. There were relapses in 16 patients. All patients relapsed at the primary intracranial sites with no spinal failures. Patients treated with whole brain irradiation had decreased 10 year PFS over those treated with local fields: 19% vs. 64% (p = 0.006). Those patients treated to > or = 50 Gy had an improved long-term PFS (p = 0.04). Multivariate analysis was undertaken with the following variables: extent of cranial irradiation, pathology, anatomic site of ependymoma, cranial irradiation dose, extent of surgery, and whether spinal irradiation was given. With PFS as the endpoint, only extent of cranial irradiation (favoring local fields) and pathology (favoring low grade ependymoma) were significant prognosticators. We conclude that carefully outlined local field irradiation is the therapy of choice, and elective spinal irradiation is of questionable benefit. PMID- 8509818 TI - Recurrent brainstem gliomas treated with oral VP-16. AB - 12 patients: (7 males and 5 females) with recurrent brainstem gliomas were treated with the oral topoisomerase inhibitor VP-16 (Etoposide). Patients ranged in age from 3 to 49 years with a median age of 7 years. All patients had been previously treated with radiation therapy (conventional fractionation: 4; hyperfractionation: 8) and 5 had received prior nitrosourea-based chemotherapy at time of tumor recurrence. Tumor recurrence was documented by radiographic tumor enlargement utilizing brain MRI with gadolinium enhancement (12) and clinical neurologic deterioration (9). Two patients underwent biopsy pathologically documenting tumor recurrence. Each cycle of therapy consisted of 21 days of VP-16 (50 mg/m2/day) followed by a 14 day rest followed by an additional 21 days of VP 16 (50 mg/m2 day). Complete blood counts were followed bi-weekly and a neurologic examination and brain MRI scan with contrast were performed prior to initiation of each cycle of therapy. Treatment related complications included: partial alopecia (5); diarrhea (5); weight loss (4); neutropenia (2); and thrombocytopenia (4). No patient required transfusion or antibiotic treatment of neutropenic fever. There were no treatment related deaths. 12 patients were evaluable of whom 6 demonstrated a radiographic response (1 complete; 3 partial; 2 stable disease) with a median duration of response of 8 months. In summary; oral VP-16 is a well tolerated and relatively non-toxic chemotherapeutic agent with apparent activity in this small cohort of patients with recurrent brainstem gliomas. PMID- 8509819 TI - Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA. AB - Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumor in vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safe in vivo and more effective than IL-2 triggering enhanced effector function in vitro. PMID- 8509820 TI - Neonatal medulloblastoma. AB - A 9-day-old female presented with a large infra- and supratentorial medulloblastoma was treated by surgery, irradiation and chemotherapy. The infant suffered from vomit a few days after birth. She was hospitalized shortly thereafter, when head enlargement was noted. A CT scan taken on admission disclosed a large mass lesion in the cerebellum, extending to the pineal portion, and marked hydrocephalus. At the age of 14 days, the patient underwent ventriculoperitoneal shunting. When she was 67 days old, the tumor was radically resected. The histopathological diagnosis was medulloblastoma. Post operatively, she was irradiated with 30 Gy to the whole brain and 20 Gy to the tumor site. As chemotherapy, ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl-3-(2-chloroethyl)-3 nitrosourea 1 mg/kg was administered twice per 6 weeks. On discharge at 7 months, her only neurological deficit was nystagmus. One week later, she could not move her legs and was readmitted. A CT scan showed no intracranial changes, but the spinal cord was swollen at Th12-L5 level. Myelography demonstrated a filling defect at the L3-5 level. Following irradiation of the spinal cord, the paraparesis gradually improved. However, her general status was deteriorating and a follow up CT scan revealed recurrence of the intracranial tumor. The patient died at the age of 9.3 months which is longer survival time than previous reported one. Neonatal brain tumors are rare, and there have been only 24 cases of neonatal medulloblastoma. The prognosis for these patients is extremely poor, regardless of treatment. Surgery, radiation and chemotherapy for neonatal medulloblastoma are discussed. PMID- 8509821 TI - Brain metastases in breast cancer; natural history, prognostic factors and outcome. AB - One hundred and thirty seven breast cancer patients with CT scan documented brain metastasis (BM) were reviewed. Occurrence of brain as first site of relapse was associated with adjuvant systemic therapy of the primary tumor. Multivariate analysis showed significantly longer survival in patients without manifest systemic disease, in patients with a solitary BM, in those with neurologic symptoms present for more than 4 weeks prior to diagnosis, and in those treated with chemotherapy after diagnosis. When controlling for prognostic factors no significant difference in survival was found between surgery and radiotherapy (RT) as treatment of a solitary lesion. Tumor size, tumor necrosis and mass effect had no demonstrable influence on survival. Overall median survival was 16 weeks and 19% survived one year. Neurologic disease was the cause of death or a major contributing factor to it in 68% of the patients, indicating the need for improvement of the treatment of BM itself. These results warrant further studies on the value of surgery, RT and chemotherapy in solitary as well as multiple BM from breast carcinoma. PMID- 8509822 TI - Phase II evaluation of echinomycin (NSC-526417) in patients with central nervous system malignancies. A Southwest Oncology Group study. AB - The objective of this trial was to determine the efficacy of echinomycin (1.2 mg/m2) administered on a weekly times four schedule in the treatment of patients with recurrent or progressive central nervous malignancies despite adequate radiotherapy. Thirty-five patients were registered on study. The majority of patients (20) had glioblastoma multiforme. Ten had anaplastic astrocytoma. Eight patients had received prior nitrosoureas. SWOG performance status was 1 in 11 patients and 2 in 22. The median age was 51 years (25-75 years). One patient had a partial remission (3%:95% confidence interval: 1%-16%). Twenty two patients had progressive disease. The median survival was 5.9 months. Toxicity was primarily gastrointestinal with nausea and vomiting in 13 patients and nausea only in 11 patients. Hepatotoxicity occurred in 10 patients. Echinomycin given at this dose and schedule is not effective in treating patients with recurrent or progressive glioblastoma multiforme or anaplastic astrocytomas. PMID- 8509823 TI - Intra-arterial mannitol infusion in the chemotherapy for malignant brain tumors. AB - To assess whether therapeutic efficacy is related to the intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for malignant brain tumors, the survival time of patients with and without mannitol infusion was compared. Ninety-eight patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B); 34 with malignant gliomas (18 in group A and 16 in group B) and 64 with brain metastases (36 in group A and 28 in group B). During radiotherapy, ACNU and CDDP at a dose of 100 mg/body were given through the common carotid artery at a rate of 20 mg/min. In group A, 50 ml of 20% mannitol was injected intra-arterially at a rate of 50 ml/min immediately prior to the injection of chemotherapeutic agents. Of the patients with malignant gliomas, the median survival time (MST) was 52 weeks for all 34 cases, 68 weeks for group A, and 47 weeks for group B. Survival analysis showed no significant differences between the two treatment groups. Of the patients with brain metastases, the MST was 40 weeks for all 64 cases, 47 weeks for group A, and 24 weeks for group B; the survival time was significantly longer in group A as compared to group B (p < 0.05). This study has demonstrated that, for the patients with brain metastases, IA mannitol infusion provided a survival benefit in the IA chemotherapy employing ACNU and CDDP. In contrast, IA mannitol infusion offered no survival benefit to the patients with malignant gliomas. PMID- 8509825 TI - Synaptic mechanisms of cortical representational plasticity: somatosensory and corticocortical EPSPs in reorganized raccoon SI cortex. AB - 1. Reorganizations of representational maps have been described for a variety of sensory and motor regions of cerebral neocortex in several species. The purpose of this study was to investigate synaptic mechanisms of the reorganizations of primary somatosensory cortex that follow removal of a digit or the joining of two digits into a syndactyly. We examined neurons in the cortical representation of digit 4 (d4). Intracellular recording was used to compare somatosensory and corticocortical excitatory postsynaptic potentials (EPSPs) in normal raccoons, with EPSPs recorded in two experimental groups of animals surviving for a mean of 22 wk after removal of d4, or union of d4 with digit 3 (d3). 2. In normal animals with d4 intact, EPSPs were evoked from this on-focus digit in 100% of cortical neurons. EPSPs were evoked from d3 and digit 5 (off-focus digits) in only a minority of neurons in normal raccoons. The incidence of somatosensory EPSPs from off-focus digits increased dramatically after removal of d4 or its union with d3. Latencies of EPSPs evoked from off-focus digits decreased after d4 removal, so that they were as short as latencies from d4 in normal animals. In contrast, for the group of animals with d3-d4 syndactyly, latencies of EPSPs from off-focus digits were not shorter than responses from these digits in normal animals. 3. Corticocortical EPSPs were no more common in animals with d4 removed than in intact animals. Furthermore, corticocortical EPSPs after d4 removal did not differ in their latencies, amplitudes, half-widths, or integrated amplitudes. The only detected change was that corticocortical EPSPs had faster rising phases after removal of d4. In contrast, after d3-d4 syndactyly, corticocortical EPSPs were more common than in normal animals. 4. Digit removal and digital syndactyly had distinctive effects on somatosensory and corticocortical EPSPs. These results do not identify unique synaptic mechanisms for cortical representational plasticity, nor do they specify the involved CNS site(s). Several synaptic mechanisms consistent with the results are considered in the DISCUSSION, including synaptic proliferation to form new synaptic connections and enhanced effectiveness of existing corticocortical synapses. PMID- 8509824 TI - Systemic chemotherapy combined with local adoptive immunotherapy cures rats bearing 9L gliosarcoma. AB - Survival of Fischer rats bearing 9L gliosarcoma in the brain was measured to determine the efficacy of 1) systemically administered chemotherapy with local adoptive immunotherapy (chemo-adoptive immunotherapy) or 2) systemically administered chemo-immunotherapy. Winn assays, where tumor instillation coincided with the start of treatment, and one-week established tumor assays were conducted. Survival of chemo-adoptive immunotherapy treated groups given intraperitoneal cyclophosphamide and intracranial lymphokine activated killer cells and recombinant Interleukin-2 was significantly extended when compared to sham treated control groups, to groups given chemotherapy with intraperitoneal cyclophosphamide, and to groups treated by local adoptive immunotherapy with intracranial lymphokine activated killer cells and Interleukin-2. The killer cells were generated from spleens of donor rats that either had or had not been given cyclophosphamide 24 h earlier. Long-term survivors (9/39), sacrificed at day 70, were obtained only in the chemo-adoptive immunotherapy treated groups; 7/39 had no histologic evidence of tumor and had focal sterile abscesses at the site of killer cell instillation. Average group weight plotted over time showed that there was acceptable toxicity with chemo-adoptive immunotherapy; the toxicity was identical to that obtained with systemic cyclophosphamide treatment. In contrast, survival of chemo-immunotherapy treated groups given systemic cyclophosphamide and Interleukin-2 was not significantly extended from groups which were sham treated or treated only with systemic Interleukin-2. Rapid decline of average group weight plotted over time and early deaths following chemo-immunotherapy treatment indicated that the regimen was toxic. The effect of cyclophosphamide administration on the splenocytes of donor rats and the LAK cells generated from them was determined by in vitro studies analyzing cell number, viability, phenotypic expression and cytotoxicity against 9L tumor. In the treatment of this intracranial neoplasm, the beneficial effects of cyclophosphamide were determined to occur in situ in the tumor-bearing host. No benefit resulted from cyclophosphamide treatment of donor rats that supplied splenocytes for LAK cell production. PMID- 8509826 TI - Time-varying mechanical behavior of multijointed arm in man. AB - 1. The aim of this study was to describe the time-varying changes in the mechanical parameters of a multijointed limb. The parameters we considered are the coefficients of stiffness, viscosity, and inertia. Continuous pseudorandom perturbations were applied at the elbow joint during a catching task. A modified version of an ensemble technique was used for the identification of time-varying parameters. Torques at the elbow and wrist joints were then modeled with a linear combination of the changes in angular position and velocity weighted by the matrix of angular stiffness and the matrix of angular viscosity, respectively. Control experiments were also performed that involved the stationary maintenance of a given limb posture by resisting actively the applied perturbations. Different limb postures were examined in each such experiment to investigate the dependence of the mechanical parameters on limb geometry. 2. The technique for the identification of limb mechanical parameters proved adequate. The input perturbations applied at the elbow joint elicited angular oscillations at the wrist essentially uncorrelated with those produced at the elbow. The frequency of oscillation is much higher at the wrist than at the elbow, mainly because of the smaller inertia. The variance accounted for by the model was approximately 80% under both stationary and time-varying conditions; in the latter case the value did not vary significantly throughout the task. In addition, the model predicted values of the inertial parameters that were close to the anthropometric measures, and it reproduced the stepwise increase in limb inertia that occurs at the time the ball is held in the hand. 3. The values of angular stiffness and viscosity estimated under stationary conditions did not vary significantly with joint angle, in agreement with previous results obtained under quasi-static postural conditions. The matrix of the coefficients of angular stiffness was not symmetrical, indicating a prominent role for nonautogenic reflex feedbacks with unequal gains for elbow and wrist muscles. 4. A complex temporal modulation of angular stiffness and viscosity was observed during the catching task. The changes in the direct coefficients of angular stiffness tended to covary with those in the coupling coefficients from trial start up to approximately 30 ms before impact time. Around impact time, however, there was a complete dissociation: the direct terms peaked, whereas the coupling terms dropped. The direct terms of angular viscosity also increased before impact, whereas the viscosity coupling terms remained close to zero throughout.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509827 TI - The neuropeptide red pigment concentrating hormone affects rhythmic pattern generation at multiple sites. AB - 1. The cardiac sac network, which controls the rhythmic contractions of the cardiac sac in the foregut of crustaceans, is distributed throughout the stomatogastric nervous system, including the oesophageal ganglion (OG), the commissural ganglia (CGs), and the stomatogastric ganglion (STG). A red pigment concentrating hormone (RPCH)-like peptide is likewise widely distributed. 2. The effects that bath application of the neuropeptide RPCH to the different ganglia has on the cardiac sac pattern were studied. 3. RPCH applied to the STG, the OG, or the CGs elicited bursting activity in all the known components of the cardiac sac pattern, including the two motor neurons, cardiac sac dilators 1 and 2 (CD1 and CD2), and the inferior ventricular nerve (ivn) fibers. 4. A cardiac sac pattern was also elicited when RPCH was applied to either the STG, the OG, or the CGs after synapses in that ganglion had been blocked by low Ca2+ saline containing 20 mM Co2+. 5. These data suggest that the ivn fibers are sensitive to RPCH and respond to it by generating bursting activity at or near their terminals in all four ganglia. 6. Application of RPCH to either the STG or the OG also caused an increase in the amplitude of the postsynaptic potential (PSP) from the ivn fibers to both CD1 and CD2. The increase was largest in the ganglion to which the RPCH was applied. 7. Repeated stimulation of the ivn, mimicking the bursts that occur during cardiac sac activity, also caused an increase in PSP amplitude, and so facilitation resulting from activation of ivn bursting could account for a portion of the increased amplitude seen in RPCH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509828 TI - Neural processing in a three-choice reaction-time task: a study using cerebral evoked-potentials and single-trial analysis in normal humans. AB - 1. Previous studies have shown that the long latency event-related potentials (ERPs) reflect certain aspects of the sensory discrimination process, although the coupling of these ERPs to the actual discrimination is variable. Indeed, we have previously shown that during a two-choice reaction time task the discrimination is accomplished as a two-stage process, with the more frequently occurring stimulus discriminated at an earlier point than the rarer stimulus. The present paper examines the hypothesis that, in a three-choice reaction time task, the discrimination is similarly organized, i.e., is accomplished with the use of a three-stage process. 2. In the present experiments, we continuously recorded the electrocerebral activity (EEG) from the scalp and the electromyogram (EMG) from the responding muscles in a three-choice reaction time task in 10 strictly right-handed subjects. EEG and EMG responses were subsequently analyzed off-line by aligning them by the onset of either the stimulus (stimulus-synchronized) or the response (response-synchronized) for both correct and incorrect responses. 3. Subjects could be classified as "fast" or "slow" responders based on the mean response-latency to the most frequently occurring of the three tones (Frequent tone). Fast responders to the Frequent tone were also fast responders to the more frequent of the rare tones (the Rare-1 tone). By contrast, the response latency to the Frequent tone did not predict the speed of response to the most rare tone (the Rare-2 tone). 4. In the response-synchronized averages well-formed premovement potentials were present for the correct responses to all three tones. In the case of the Frequent tone, these potentials were symmetrical over the two cerebral hemispheres (as expected because both hands responded to this tone). They began > or = 200 ms before the average onset of the stimulus, suggesting that the preparation to respond preceded the stimulus. In the case of the two rare tones, the amplitudes of these premovement potentials were asymmetrical over the two hemispheres. For the Rare-1 tone, these potentials were lateralized to the hemisphere contralateral to the hand moved. For the Rare-2 tone, however, these premovement potentials were initially lateralized to the ipsilateral hemisphere, indicating that, even when subjects were able to respond rapidly and correctly to this tone, they were anticipating a need to respond with the incorrect hand (in anticipation of the more frequent Rare-1 tone).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509829 TI - Long-term dysfunctions of neural stereoscopic mechanisms after unilateral extraocular muscle proprioceptive deafferentation. AB - 1. Neural correlates of the permanent deficits in depth perception that occur when extraocular muscle proprioceptive (EMP) afferents are interrupted unilaterally in kittens were investigated by performing extracellular recordings in the primary visual cortex (area 17) in adulthood. Unilateral section of the ophthalmic branch of the trigeminal nerve (V1 nerve) were performed in 11 cats when they were between 5 and 12 weeks of age (uni-V1 group). Electrophysiological results were compared with those obtained in 17 normal adult cats (control group). 2. Binocular interactions were assessed by testing the sensitivity of cortical neurons to dichoptic presentations of moving sine-wave gratings whose interocular positional phase relationship was randomly varied. The amplitude modulation between the minimum and the maximum binocular responses defined the dynamic range. The degree of binocular suppression or facilitation was assessed by comparing these binocular response limits with the optimal monocular responses evoked through either eye at the best spatial frequency. The variability of both monocular and binocular responses was estimated by using the variation coefficient. 3. In uni-V1 cats, both the dynamic range and the degree of binocular suppression were significantly less pronounced than in controls, whereas binocular facilitation was not affected. The variability of the binocular responses was significantly increased, unlike monocular responses, whose variability was similar to control values. 4. From Fourier analysis of the poststimulus time histograms, two clear-cut categories of cells emerged that were differentially affected in the uni-V1 group. The "modulated" cells showed significantly less binocular suppression than in controls, and the "unmodulated" cells had binocular responses that were significantly more variable than in controls. Results from "simple" cells were similar to those of modulated cells, and results from "complex" cells were similar to those of unmodulated cells. However, in the unmodulated population, which was composed of both simple and complex cells, it was shown that the increase of variability was due to that of complex cells. 5. A nonparametric statistical test was applied on the interocular phase shift tuning curves to determine the minimum stimulus change necessary to elicit a significant change in the neural response. Two categories of cells were determined: the "discriminative" cells (80% in controls but 45% in uni-V1 cats) combined pronounced binocular suppression and dynamic range with relatively low variability. The reverse was true in the case of "nondiscriminative" cells (20% in controls and 55% in uni-V1 cats). 6. In uni-V1 cats, about half of the cells were monocularly activated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509830 TI - Nucleus Z: a somatosensory relay to motor thalamus. AB - 1. It was the aim of this study to show that nucleus Z of the cat medulla acts as a relay between the spinal cord and the ventral lateral (VL) nucleus of the motor thalamus. For this purpose, extracellular recordings were made from neurons that were antidromically identified by stimulation in the rostral thalamus, particularly VL, and orthodromically activated by electrical stimulation of the spinal cord and/or natural stimulation of the hindlimb. The electrophysiological work was complemented by anatomic work. Here, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into nucleus Z and the termination sites of bulbothalamic projections were anterogradely labeled. 2. A total of 120 neurons were antidromically identified as projecting to thalamus: 101 to VL and 19 outside VL. The recording sites in nucleus Z were marked by dye injection or by electrolytic lesion. They were confined to a small region (roughly 1 mm in diameter), 2.8-3.7 mm rostral to obex, 2.9-3.8 mm lateral from the midline, and from the surface of the medulla to a depth of 1 mm. The antidromic latencies ranged between 0.8 and 3.2 ms, with no difference in latencies associated with location of neurons in nucleus Z or thalamic projection sites. 3. Injection of WGA-HRP labeled fibers and axon terminals in the contralateral thalamus. Terminal labeling was densest in the lateral parts of the mid- and caudal region of the VL nucleus and, to a lesser extent, in the adjacent rostrodorsal part of the ventro posterior lateral (VPL) nucleus. The sites of terminal labeling in VL corresponded with location of antidromic stimulation sites. 4. Orthodromic activation of nucleus Z neurons was tested in response to electrical stimulation of the ipsilateral dorsolateral funiculus (which includes the dorsal spinocerebellar tract) and/or the dorsal columns. All neurons responded to stimulation of the dorsolateral funiculus (45/45). The responsiveness of 44 neurons was tested to stimulation of the dorsal columns. Only 8 of 44 tested responded with a discharge. The orthodromic latencies of unitary discharges ranged from 1.1 to 4.4 ms to stimulation of the dorsolateral funiculus, and from 1.1 to 4.9 ms to stimulation of the dorsal columns. Most responses are likely to be monosynaptic. Differences in latencies were not associated with location of recording sites or thalamic projection sites of nucleus Z neurons. 5. The responsiveness of many neurons (n = 84) was tested to natural stimulation of the ipsilateral hindlimb (which provides the sensory input to nucleus Z).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509831 TI - Early postnatal development of visual function in ganglion cells of the cat retina. AB - 1. Spontaneous and visually evoked action potentials were recorded from single retinal ganglion cells in superfused retina-eyecups prepared from cats between postnatal day 5 (P5) and adulthood. The development of functional responses was studied quantitatively with contrast-modulated spots and sinusoidal grating stimuli. Some functionally characterized cells were impaled and injected intracellularly with horseradish peroxidase to permit direct structure-function comparisons during the period of synaptogenesis and the expression of transient morphological features. 2. Around the time of eye opening at postnatal day 7 postnatal day 10, the spontaneous discharge of ganglion cells was characterized by bursts of action potentials separated by periods of no activity lasting up to tens of seconds. This "burst-type" pattern gradually changed to a more regular spontaneous discharge during the first 2-3 postnatal wk. The burst-type discharge was completely blocked by 10 mM Mg2+, but was largely unaffected by bath application the excitatory amino acid receptor antagonist 6-cyano-7 nitroquinoxaline-2,3- dione at concentrations that eliminated both spontaneous and light-driven activity of cells that had developed a regular spontaneous discharge. DL-2-amino-7-phosphonoheptanoic acid, a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, also had little effect on the burst-type discharge but did block the depolarizing effects of exogenous NMDA. These results demonstrate that the burst-type spontaneous discharge is a calcium-dependent process but probably is not mediated by synapses utilizing receptors for excitatory amino acids. 3. On P5, a minority of ganglion cells responded to a light stimulus delivered to the retina at the electrode tip. The percentage of responsive cells increased over time so that all cells responded by P10. During this transition period, the light responses were often weak, fatigued with repeated stimulation, and displayed poor temporal resolution. There was a rapid increase in the briskness of the response to a standard light stimulus during the second through fourth postnatal weeks. However, cells that responded sluggishly to visual stimulation were observed at all ages studied. 4. Both ON- and OFF-type receptive field (RF) centers were observed in approximately equal numbers as soon as the light response developed, and the proportion of the two types was independent of age. Three percent (10/342) of visually responsive ganglion cells had ON-OFF RFs, and the incidence of this type also appeared to be invariant with age.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509832 TI - Cutaneous sensory receptors in the rat foot. AB - 1. A total of 574 cutaneous afferent units in the sural and plantar nerves supplying the skin of the rat foot was examined: 399 A beta-units, 55 A delta units, and 120 C-units. Their receptive-field (RF) properties were similar to those described in other mammals. However, the receptor type composition of units was different between the two nerves. 2. The sural A beta-fiber sample (n = 160) consisted of G-hair (41%), field (11%), rapidly adapting (RA; 6%), slowly adapting type I (SA-I; 7%), and type II (SA-II; 35%) mechanoreceptors. The plantar A beta-fiber sample (n = 239) was composed of G-hair (3%), RA (35%), SA-I (30%), SA-II (24%), and Pacinian corpuscle (PC; 8%) mechanoreceptors. 3. The RFs of SA-II units were located on both hairy and glabrous skin overlying the foot joints. Many of the SA-II units responded to movement of the foot joints. The RFs of both SA-I and RA units were small in size and located in high density on the toe tips and footpads. PC units were very sensitive to vibration and had extremely large RFs as in other species, although they were rare and found only in the plantar nerve. Field units were similar to SA-II units in response properties and RF distribution. 4. The sural A delta-fiber sample (n = 44) included nociceptors (68%), D-hair (27%), and cold (5%) receptors. All sampled plantar A delta-fibers (n = 11) were nociceptors. Of A delta-nociceptor units, A delta-mechanical nociceptors (73%) were dominant. 5. The sural C-fiber sample (n = 85) included nociceptors (44%), C-mechanoreceptors (33%), and cold receptors (21%). The plantar C-fiber sample (n = 35) included nociceptors (77%) and cold receptors (23%). No warm units were found among either the sural or plantar nerve fibers. Of C-nociceptors, C-mechanoheat nociceptors (80%) were dominant. 6. The results indicate that all well-known types of cutaneous receptors, except warm receptors, exist in the foot skin of the rat. On the basis of the fact that RFs of RA and SA-I units are in high density on the toe tips and footpads, it is suggested that those regions may have a spatial discriminating capacity. It is also suggested that SA-II receptors may play a role in proprioception, because they have RFs on the skin over foot joints and respond to joint movement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509833 TI - Wipe and flexion reflexes of the frog. I. Kinematics and EMG patterns. AB - 1. We evaluated the hypothesis that the neural control of complex motor behaviors is simplified by building movement sequences from a series of simple neural "building blocks." In particular, we compared two reflex behaviors of the frog, flexion withdrawal and the hindlimb-hindlimb wipe reflex, to determine whether a single neural circuit that coordinates flexion withdrawal is incorporated as the first element in a sequence of neural circuits comprising the wipe. The neural organization of these two reflexes was compared using a quantitative analysis of movement kinematics and muscle activity patterns [electromyograms (EMGs)]. 2. The three-dimensional coordinates of the position of the foot over time and the angular excursion of hip, knee, and ankle joints were recorded using a WATSMART infrared emitter-detector system. These data were quantified using principal components analysis to provide a measure of the shape (eigenvalues) and orientation (eigen-vector coefficients) of the movement trajectories. The latencies and magnitudes of EMGs of seven muscles acting at the hip, knee, and ankle were analyzed over the interval from EMG onset to movement onset, and EMG magnitudes during the initial flexion of the limb. These variables were compared during flexion withdrawal and the initial flexion movement of the limb during the hindlimb-hindlimb wipe reflex (before the onset of the frequently rhythmic portion when the stimulus is removed) when the two reflexes were elicited from comparable stimulus locations. 3. In both the flexion reflex and the initial movement segment of the wipe reflex, the foot moves along a relatively straight line. However, the foot is directed to a more rostral and lateral position during flexion than during wipe. All three joints flex during flexion withdrawal, whereas during the wipe, the knee and ankle joints flex but the angular excursion of the hip joint may vary. The different orientations of the movement trajectories are associated with EMG patterns that differ in both timing and magnitude between the two reflexes. 4. The differences in the kinematics and EMG patterns of the two reflexes during unrestrained movements make it unlikely that the neural circuit that coordinates flexion withdrawal is incorporated as the first element in the sequence of neural circuits underlying the wipe reflex. 5. Unlike the wipe reflex, during flexion withdrawal there is no apparent constraint on the accuracy of placement at the end of the movement, yet the animals nevertheless achieved consistent final positions of both the foot and of each joint. The implications of these findings with respect to the controlled variables are discussed. PMID- 8509834 TI - Wipe and flexion reflexes of the frog. II. Response to perturbations. AB - 1. To evaluate the hypothesis that the neural control of sensorimotor transformations may be simplified by using a single control variable, we compared the movement kinematics and muscle activity patterns [electromyograms (EMGs)] of the frog during flexion withdrawal and the hind limb-hind limb wipe reflex before and after adding an external load. In addition, the flexibility of spinal cord circuitry underlying the hind limb-hind limb wipe reflex was evaluated by comparing wipes before and after removal of one of the contributing muscles by cutting a muscle nerve. 2. The kinematics of the movements were recorded using a WATSMART infrared emitter-detector system and quantified using principal components analysis to provide a measure of the shape (eigenvalues) and orientation (eigenvector coefficients) of the movement trajectories. The neural pattern coordinating the movements was characterized by the latencies and magnitudes of EMGs of seven muscles acting at the hip, knee, and ankle. These variables were compared 1) during flexion withdrawal and the initial movement segment of the limb during the hind limb-hind limb wipe reflex in both unrestrained movements and in movements executed when a load equal to approximately 10% of the animal's body weight was attached to a distal limb segment and 2) during the initial movement segment of the wipe reflex before and after cutting the nerve to the knee flexor-hip extensor, iliofibularis. 3. Addition of the load had no discernible effect on the end-point position of the foot during either reflex. However, during the loaded flexion reflex, the ankle joint did not move until after the hip and knee joints had moved to their normal positions. This delayed flexion of the ankle was accompanied by large increases in the magnitude of EMG activity in two ankle muscles that exceeded the levels found during unrestrained movements. Significant changes in the temporal organization of the EMG pattern accompanied the change in joint angle relations during flexion withdrawal. 4. Despite the addition of an external load, all animals successfully and reliably removed the stimulus during the wipe reflex, and the relative timing of both the EMG pattern and joint angle motion was preserved. 5. Immediately after section of the nerve to a single muscle (iliofibularis), all animals successfully and reliably removed the stimulus during the wipe reflex. The relative timing of muscle activation was preserved, accompanied by a reduction in the activity level of gluteus magnus, a muscle with action reciprocal to iliofibularis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8509835 TI - Free nerve ending terminal morphology is fiber type specific for A delta and C fibers innervating rabbit corneal epithelium. AB - 1. A delta and C fibers are the smallest diameter and most numerous axons in peripheral nerve bundles. They have been thought to terminate as "free" nerve endings lacking organized structure. The present study used a vital fluorescent dye to selectively visualize living free nerve endings innervating rabbit corneal epithelium, allowing structure to be correlated with electrophysiological and functional characteristics. 2. Conduction velocity measurement of visually identified nerve endings were used to discriminate between C and A delta fibers. C fiber sensory endings terminated as short (< 50 microns) vertically directed processes clustered within the epithelium. A delta fibers terminated as long (0.1 1.2 mm) horizontal processes running parallel to the epithelial surface. 3. Only A delta fiber endings were mechanoreceptive, and the unique elongated structure imparted directional selectivity. Comparison of physiological and electrical activation indicated that mechanical stimuli were transduced in < 600 microseconds. This study confirms previous suggestions of structural and functional specialization for "free" nerve endings. PMID- 8509837 TI - Practical procedures and pharmacological applications of quantitative PET. PMID- 8509836 TI - Noninvasive arterial monitor for quantitative oxygen-15-water blood flow studies. AB - A noninvasive monitor has been developed for monitoring arterial radioactivity in quantitative PET studies of blood flow. The significance of this probe is that quantitative blood flow studies can be performed without the use of arterial catheterization. The method employed is based on the flux of photons emanating from the superior lobe of the right lung following an intravenous bolus of H2(15)O. Calibration of the monitor is obtained by measuring the relationship between lung monitor counts and arterial radioactivity after arterial and venous radioactivity levels have equilibrated following inhalation of C15O. To determine the accuracy of the lung probe as a measure of arterial radioactivity, 44 brain blood flow determinations were made in 11 volunteers using arterial radioactivity measures based both on the lung probe and continuous sampling from a radial artery. Repeated measures analysis of variance found no differences between invasive and noninvasive estimates of blood flow. These results suggest that the lung monitor enables quantitation of cerebral blood flow yet avoids the trauma of an arterial puncture. PMID- 8509838 TI - SPECT and MRI in posterior cerebral artery infarction and related visual field defects. PMID- 8509839 TI - Approaches to identify and characterize hypertrophic myocardium. PMID- 8509840 TI - Immunoadsorption: an enhancement strategy for radioimmunotherapy. PMID- 8509841 TI - Radiolabeled antibodies as cancer therapeutics. PMID- 8509842 TI - Diuretic renography. PMID- 8509843 TI - People in nuclear medicine: an interview with Fred Bonte. PMID- 8509844 TI - People in nuclear medicine: an interview with John Kuranz. PMID- 8509845 TI - People in nuclear medicine: an interview with Arthur M. Weis. PMID- 8509846 TI - People in nuclear medicine: an interview with Wil B Nelp. PMID- 8509847 TI - People in nuclear medicine: an interview with Michael J Welch. PMID- 8509848 TI - People in nuclear medicine: an interview with Barry A Siegel. PMID- 8509849 TI - Energy Department proposes two isotope initiatives. PMID- 8509850 TI - Report hints at restructuring of DOE isotope program. PMID- 8509851 TI - Early closing of accelerator could impede nuclear medicine research. PMID- 8509852 TI - Characterization of the reinjection thallium image. AB - The 201TI image after reinjection was characterized by analysis of stress and reinjection data acquired in 204 consecutive patients undergoing planar 201TI cardiac stress tests. In an additional 63 patients, redistribution data were also acquired to determine the effect of washout on the final reinjection image. Maximum count densities for the myocardium, lung and liver were measured, and the ratios between the stress and redistribution and the stress and reinjection sets of data were calculated. In patients with < 5% probability of coronary artery disease (CAD) ("normal" group), the reinjection image was typified by less myocardial activity (initial/reinjection = 1.22), slightly less lung activity (initial/reinjection = 1.05) and greater hepatic activity compared to the initial postexercise image. In male patients with > 5% probability of CAD, peak myocardial activity after reinjection was affected by the following variables: the interval between stress and reinjection, the amount of the initial dose and the 201TI scan results (normal 201TI study: initial/reinjection = 1.16; abnormal = 1.06; p < 0.009). Myocardial activity after reinjection was linearly related to myocardial activity after redistribution (r = 0.82). There was no significant influence by those variables in the 76 women who were studied. In conclusion, myocardial 201TI was decreased after reinjection in normal patients. The results indicate that there is an increased likelihood of underlying CAD in male patients undergoing exercise stress tests when 201TI myocardial activity on reinjection is greater than on the initial image. PMID- 8509853 TI - Value of dobutamine technetium-99m-sestamibi SPECT and echocardiography in the detection of coronary artery disease compared with coronary angiography. AB - The value of dobutamine echocardiography and 99mTc-sestamibi SPECT imaging was evaluated as a noninvasive diagnostic method for assessing coronary artery disease (CAD). Twenty-seven patients who underwent coronary angiography were submitted to two separate injections of 99mTc-sestamibi, one under control conditions and the other after reaching a peak dobutamine infusion rate. Simultaneous ECG and echocardiographic monitoring was also performed during stepwise dobutamine infusion. Whereas the overall sensitivity and specificity of dobutamine sestamibi SPECT imaging were 94% and 88%, these values for dobutamine ECG and echocardiography were 61%, 55% and 84%, 88%, respectively. When dobutamine echocardiography and 99mTc-sestamibi SPECT imaging were evaluated together, the diagnostic accuracy reaches almost 100%. Dobutamine echocardiography is of value in determining ischemic threshold earlier than clinical symptoms and allows simultaneous evaluation of ventricular performance and contractile function associated with perfusion abnormalities on 99,Tc sestamibi SPECT imaging. Our experience shows that 99mTc-sestamibi SPECT imaging, when combined with dobutamine echocardiography, is a safe, practical, well tolerated method with high diagnostic accuracy for the evaluation of CAD. PMID- 8509854 TI - High technology squared: you saw it here. PMID- 8509855 TI - Plasma D-dimer: a useful tool for evaluating suspected pulmonary embolus. AB - Although ventilation-perfusion lung scanning is widely used in evaluating patients with suspected pulmonary embolus, additional rapid screening tests are needed to supplement scintigraphy in patients in whom the scan is indeterminate or the scan results are discordant with clinical suspicion. D-dimer is a fibrin degradation product which should be elevated in the presence of intravascular coagulation. We prospectively studied patients referred for lung scanning by obtaining a plasma D-dimer latex agglutination assay at the time of the scan. Of 64 patients who had pulmonary angiography to confirm the diagnosis, 16 were positive for pulmonary embolus and only one had a normal D-dimer. The D-dimer was normal in 27 of 48 patients without embolus and elevated in 21. Although an elevated D-dimer level is a nonspecific finding, we conclude that a normal D dimer is a good negative predictor for pulmonary embolus, with a negative predictive value of 0.97. PMID- 8509856 TI - SPECT and planar brain imaging in crack abuse: iodine-123-iodoamphetamine uptake and localization. AB - The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse. PMID- 8509857 TI - Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials. AB - Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs. PMID- 8509858 TI - Characterization of iodovinylmisonidazole as a marker for myocardial hypoxia. AB - Misonidazole and related compounds are metabolically trapped in viable cells as a function of reduced cellular pO2. [18F]fluoromisonidazole has been used to detect hypoxia in the heart and in tumors noninvasively with positron emission tomography. The purpose of this study was to characterize the uptake of the iodinated misonidazole congener iodovinylmisonidazole (IVM) in ischemic myocardium. In six open chest dogs (Group 1), the left anterior descending (LAD) coronary artery was partially occluded and in four dogs (Group 2), demand ischemia was produced by the combination of atrial pacing and catecholamine infusion in the presence of a LAD stenosis. [131I]IVM (5-15 microCi/kg, i.v.) was given following the onset of ischemia. Tracer deposition was measured by postmortem tissue sampling 4 hr postinjection and compared to microsphere myocardial blood flow (MBF) measurements made at baseline and at 2 hr postinjection. In Group 1, regional IVM deposition in heart samples within the ischemic area was inversely related to MBF with maximum tissue:blood ratios of 3.2. For a given level of reduced blood flow, IVM uptake was higher in the subendocardium indicating a greater vulnerability of the subendocardium to reductions in oxygen delivery. In Group 2, enhanced IVM deposition was detected as a result of demand ischemia, even in some regions where absolute flow was normal or increased from baseline, indicating that flow per se is not the principal determinant of tracer uptake. We conclude that IVM is a promising marker for myocardial hypoxia with potential clinical application using gamma camera imaging. PMID- 8509859 TI - Is nuclear medicine viable and can it measure viability? PMID- 8509860 TI - Myocardial extraction of technetium-99m-[2-(1-methoxybutyl) isonitrile] in the isolated rabbit heart: a myocardial perfusion agent with high extraction and stable retention. AB - Technetium-99m-[2-(1-methoxybutyl) isonitrile] (MBI) is a potential new compound for the scintigraphic imaging of coronary flow. Evaluation in the blood-perfused isolated rabbit heart model showed this compound to have a myocardial uptake comparable to 201Tl and higher than sestamibi. Although the mean +/- s.d. maximum extraction (Emax) and capillary permeability-surface area product (PScap) of 99mTc-MBI (Emax = 0.45 +/- 0.10, PScap = 1.07 +/- 0.47 ml/min.g) were much less than 201Tl (Emax = 0.71 +/- 0.07, PScap = 2.21 +/- 0.76 ml/min.g, p < 0.0001), the net extraction of 99mTc-MBI (Enet = 0.52 +/- 0.10) was only slightly less than the value for 201Tl (Enet = 0.56 +/- 0.10, p < 0.05). There was no significant difference in the myocardial uptake versus flow between 99mTc-MBI and 201Tl. These data indicate that assessment of relative coronary flow based on the myocardial uptake of 99mTc-MBI should give results comparable to 201Tl. Therefore, 99Tc-MBI may have clinical potential as a radiolabeled myocardial perfusion agent. PMID- 8509861 TI - Evaluation of indium-111- and yttrium-90-labeled linker-immunoconjugates in nude mice and dogs. AB - Rapid uptake and slow transit of radioactivity from normal organs are detrimental to any clinical utilized radioimmunoconjugate because they lower the target-to nontarget ratio and deliver undesirable radiation to normal organs. To mitigate this problem, two labile chemical linkages (EGS and DST) were introduced between a monoclonal antiferritin antibody (QCI) and a chelating agent (DTPA). The biodistribution of labile-linker immunoconjugates (EGS and DST) and stable linker immunoconjugates (DSS and ITCB) were compared. In a nude mouse model, all of the four immunoconjugates labeled with 111In targeted subcutaneously-implanted human tumor cells. Tumor-to-normal organ ratios were enhanced for the EGS linkage in comparison to the two stable linkages. Serial whole-body immunoscintigraphy confirmed the biodistribution study. The EGS and ITCB 90Y-labeled immunoconjugates had biodistributions similar to their respective 111In-labeled immunoconjugates. As the mouse model is not representative of the high uptake of monoclonal antibodies in the human liver, beagle dogs were used to further explore the retention of radiolabel in normal liver. The EGS-linked immunoconjugate significantly reduced the dog liver activity when compared to the ITCB immunoconjugate. The combination of the animal models (mouse and dog) appears to allow for a more compete and optimal preclinical analysis of chelated radiolabeled monoclonal antibodies for diagnosis or treatment and illustrates the potential clinical improvements possible with labile chemical linkages in radioimmunoconjugates. PMID- 8509862 TI - Site-specific/stable radioiodination of 1,2-Pal-3-IPPA: an agent for the potential clinical evaluation of pancreatic insufficiency by urine analysis. AB - To measure pancreatic lipase activity, we synthesized a triglyceride containing a radioiodinated fatty acid. The urinary excretion of radioactivity was measured in five rats following administration of the agent by feeding tube. We attached 15 phenylpentadecanoic acid (PPA) to position-3 of 1,2-dipalmitoyl-rac-glycerol (1,2 Pal) to form 1,2-Pal-3-PPA. The 1,2-Pal-3-IPPA (expected lipase substrate) was prepared by the thallation-iodide displacement method. In a dual-label study, the 125I-1,2-Pal-3-IPPA triglyceride was administered with the 131I-IPPA free acid to rats (n = 5) by oral gavage. Urine and feces were collected daily and the tissue distribution of both tracers was evaluated over a five-day period. A significant portion of the administered activity was excreted in 24 hr in the urine (125I, 30.31% + 4.32%; 131I, 35.0% + 7.29%), which cochromatographed with hippuric acid by thin layer chromatography. Release of the acidic components from the conjugated excretory products by acid hydrolysis of the urine provided the radioactive acidic metabolites. Analysis of the Folch extracts of fat samples demonstrated that the radioactive components cochromatographed in the triglyceride region. This agent appears useful for the evaluation of various gastrointestinal diseases. PMID- 8509863 TI - Demonstration of unilateral sialadenitis on postradiotherapy gallium-67-citrate imaging. AB - Intense, asymetric uptake of 67Ga-citrate in the right parotid and submandibular glands was observed in an asymptomatic patient who had undergone locoregional radiotherapy for Stage IA Hodgkin's disease 8 mo earlier. In view of the modified minimantle radiation field and adjunctive 99mTc salivary imaging, a unilateral radiation-induced sialadenitis best explained this unusual scintigraphic appearance. PMID- 8509864 TI - The unsuspected complications of bacterial endocarditis imaged by gallium-67 scanning. AB - In this case report, we present a patient with bacterial endocarditis who was evaluated by 67Ga imaging for persistent fever despite treatment with multiple intravenous antibiotics. Although evidence of bacterial endocarditis was absent with 67Ga imaging, the study demonstrated findings that represent complications of bacterial endocarditis. The procedure demonstrated moderate pericardial uptake of isotope and thus provided the first evidence of pericarditis which was later confirmed at surgery. The study also demonstrated mildly increased activity in the vicinity of the aortic root and right atrium. A sinus of valsalva abscess, complicating the underlying diagnosis of bacterial endocarditis, was found and treated with surgery and antibiotics. At autopsy 4 wk later, a persistence sinus of valsalva abscess was found which extended into the right atrium. PMID- 8509865 TI - Successful gallium-67 imaging of North American pulmonary blastomycosis. AB - South American blastomycosis (Paracoccidioidomycosis) has been previously imaged using 67Ga imaging. We present a case of North American pulmonary blastomycosis successfully imaged with 67Ga. Clinical, radiologic and biopsy findings are correlated. PMID- 8509866 TI - Verification of a varying threshold edge detection SPECT technique for spleen volume: a comparison with computed tomography volumes. AB - SPECT enables quantitation of organ volume with radionuclide techniques using threshold edge detection methods. Previous phantom studies showed that a negative correlation exists between volume and threshold value. In those studies, the use of calibration curves were believed to correct for volume dependence on threshold values. The aim of this study was to evaluate the accuracy of spleen volume determination in 20 patients with SPECT by employing a varying threshold edge detection technique with volumes derived from CT. All patients had both radionuclide and CT examinations that were reconstructed with a filtered backprojection algorithm. During SPECT reconstruction, transverse slices were obtained with attenuation correction (Method A) and without attenuation correction (Method B). CT volumes were calculated from manually drawn regions of interest, whereas SPECT volumes were calculated with an automated algorithm using previously determined calibration curves. A confidence interval for calculated SPECT volumes also was calculated because of possible errors in the threshold value. The spleen volumes studied ranged from 91.2 ml to 1660.1 ml. Regression analysis yielded equations of CT = 0.97 SPECT + 7.07 (r = 0.996) and CT = 1.05 SPECT - 19.25 (r = 0.990) between CT and SPECT spleen volumes with a standard error of the y estimates of 31.10 ml and 54.47 ml, respectively. A mean percentage difference of 10.5% +/- 7.6% and 11.4% +/- 6.6% in spleen volume was obtained for Methods A and B in comparison with CT spleen volumes. The threshold value varied between 40.9% and 32.4% for Method A and between 41.2% and 28.5% for Method B because the spleen volume is increased. The varying threshold edge detection technique described in this paper can be implemented successfully in the clinical setting. PMID- 8509867 TI - An automated analysis program for the evaluation of cardiac PET studies: initial results in the detection and localization of coronary artery disease using nitrogen-13-ammonia. AB - Positron emission tomography (PET), in combination with myocardial blood flow tracers, allows highly accurate diagnosis of coronary artery disease using visual data interpretation. To increase the objectivity of data analysis and to reduce interobserver variability, we developed an automated analysis method for the three-dimensional definition of myocardial activity, which includes true volumetric data extraction and mathematical constraints of activity sampling to the expected shape of the left ventricle. Data are displayed in a standardized polar map or three-dimensional format for comparison with a normal database. The first clinical evaluation of this method in 52 patients using receiver operating characteristics (ROC) curve analysis demonstrated high diagnostic accuracy for detection as well as localization of coronary artery stenosis in predefined vascular territories. The interobserver and intraobserver agreement for localization of disease was excellent, with correlation coefficients varying from 0.85 to 0.99 for individual vascular territories. Thus, this automated quantitative analysis program provides highly accurate and reproducible evaluation of cardiac PET flow studies. Definite determination of its diagnostic accuracy requires a prospective multicenter trial in a larger patient population employing the criteria for abnormality established in this initial clinical evaluation. PMID- 8509868 TI - What should we expect from cardiac PET? PMID- 8509869 TI - Quantification of myocardial muscarinic receptors with PET in humans. AB - The potential for noninvasive quantification of myocardial muscarinic receptors using PET data, a mathematical model, multi-injection protocols and 11C-labeled methylquinuclidinyl benzilate (MQNB) as a radioligand was previously demonstrated in dogs. The present study examines the possibility of optimizing the experimental protocol to make this approach suitable for human studies. For six normal subjects, the protocol included three injections: a tracer injection, followed 30 min later by an injection of an excess of unlabeled MQNB (displacement) and then 30 min later by a simultaneous injection of unlabeled and labeled MQNB (coinjection). The model input function was estimated from the PET data corresponding to the left ventricular cavity. This protocol enables a separate evaluation of all parameters of a ligand-receptor model which includes three compartments and seven parameters. The complexity of this three-injection protocol, however, appears to be inconvenient for clinical use. A simplified two injection protocol (tracer injection and coinjection) was evaluated in five other normal subjects and the results were compared to those obtained with the three injection protocol. In regions of interest over the left ventricle, the mean value of the receptor concentration B'max and the equilibrium dissociation constant Kd were 26 +/- 7 pmole/ml tissue and 2.0 +/- 0.5 pmole/ml tissue, respectively. The possible existence of nonspecific binding was studied in two subjects using a double-displacement protocol. The corresponding rate constant was found to be very low (0.03 min-1). PMID- 8509870 TI - Phantom study of breast tissue attenuation in myocardial imaging. AB - The attenuation of photons by the breasts and other soft tissue overlying the chest may decrease the diagnostic accuracy of SPECT myocardial imaging. In this experiment, we measured the attenuation distortion of myocardial polar maps using a thorax phantom with a cardiac insert and added breast tissue. The distortion was measured using a regional semiquantitative analysis. Attenuation compensation was performed using a conebeam radionuclide CT attenuation map. Breast tissue attenuation created apparent "defects" in the polar map, where the intensity was reduced by up to 35% relative to the most intense region. However, the size, location and severity of the reduction depended on cardiac insert orientation and breast placement. For the geometries studied, apparent "defects" were observed in the anterior wall, the apex, the inferior wall and basal regions. These results suggest that attenuation artifacts may occur in almost any location. However, the attenuation compensation nearly eliminated the apparent defects and improved polar map symmetry. After compensation, the variations between regions were generally 5% or less. Therefore, we expect that attenuation compensation will improve diagnostic accuracy in myocardial imaging in female patients and in males with excessive musculature or soft tissue. Without such compensation, diagnosis may be compromised. PMID- 8509871 TI - Bone imaging with energy-weighted acquisition. AB - Scattered radiation is the principal cause of image degradation in nuclear imaging. Several strategies have been tried to reduce the contribution of scattered radiation in nuclear imaging including energy-weighted acquisition (EWA). EWA reduces the effect of scattered radiation by assigning a positive value for primary photon and a negative value for scattered radiation. The effect of EWA for lesion detection on bone scans was compared with a standard acquisition protocol, referred to as normal weighted acquisition (NWA), in 97 patients by simultaneously acquiring bone scan images using both protocols. EWA identified 436 lesions (mean 4.49) and NWA 415 lesions (mean 4.28). There was no statistical difference in the number of lesions identified nor in the intensity of uptake in these lesions when assessed qualitatively. Therefore, it is concluded that EWA does not enhance lesion detection on 99mTc bone scans. PMID- 8509872 TI - Facilitating innovation at the unit level through cultural assessment, Part 2: Adapting managerial ideas to the unit work group. AB - The culture of an organization is a powerful force to contend with in transforming a healthcare system. Culture can either drive or restrain innovation: sometimes cultural values support innovation; but culture can restrain innovation when there is conflict between the culture and the innovation. Part 1 of this series (April 1993) examined the concept of organizational culture fail to materialize when the work group culture is not considered while implementing change. This article uses research data to illustrate a five-step cultural innovation process. The creative nursing unit manager can use the process to implement a variety of practice patterns to help the healthcare organization remain competitive and increase the quality of its care. These practice patterns include team nursing, primary nursing, case management, managed care, patient-centered care, assistive personnel, and computer-assisted care. PMID- 8509873 TI - Implementing a managed care framework through care maps. AB - Managed care frameworks are a viable approach to quality improvement initiatives. The author discusses one hospital's experience with care maps as the tool used to implement managed care. A patient care guide for open heart surgery patients is used to illustrate patient and family involvement in care. PMID- 8509874 TI - Who's on first? Shared governance in the role of nurse executive. AB - After the resignation of their vice president for patient care services, five motivated directors of nursing accepted the challenge of launching an innovative and unconventional approach to nursing management. Using a shared governance framework and a medical staff model, they jointly assumed responsibility for the vice president position of a 415-bed regional medical center by rotating through the position annually. PMID- 8509876 TI - New study of nurse vs. physician care shows nurses offer same or better treatment at lower costs. PMID- 8509875 TI - Job descriptions for differentiated nursing practice and differentiated pay. AB - Compensation of nurses in differentiated practice is based on distinctive job descriptions. The employer can then pay according to education, position, and actual performance level and seek to hire the staff mix that is most cost effective for the institution. Both staff nursing and manager job descriptions are presented in this article. The authors discuss generic job descriptions that differentiate the practice of the staff nurse and the nurse unit manager according to the incumbent's educational level. PMID- 8509877 TI - Five guiding principles for primary healthcare. PMID- 8509878 TI - Chaos or transformation? Managing innovation. AB - Nurse innovation is the key to transformation of the healthcare organization and the healthcare system. This article offers the nurse executive and the leadership team a way to assess innovative tendencies of their department or organization and determine where strengths and trouble spots exist. The author discusses a five-phase innovation management process with suggested interventions for each phase. PMID- 8509879 TI - Hospital closure: reflections of a former nurse executive. AB - In this interview, a former nurse executive describes her experiences as she participated in the closing of a hospital. She describes the sequence of selected events, some of her feelings, and feelings that were experienced by staff as they continued to provide services while dismantling the organization. She associates these feelings with those that occur in crises associated with stressful events. Recommendations are offered that should be helpful to nurse executives in similar situations. PMID- 8509880 TI - The chief nurse officer as a board member: membership duties. AB - This series will explore the different types of governing bodies, with their attending responsibilities, on which chief nurse officers serve. A comparison of the administrative nature of the governing body with executive management will be described relative to legal, risk management, ethical, and liability concerns. Exploration of potential and actual conflicts that nurse executives who are board members may confront will also be highlighted. Chief nurse officers, who are board members, will discuss the required investments and benefits of board membership. PMID- 8509881 TI - Tax-deductible education expenses. AB - Nurse executives facilitate employees' educational development with advice concerning financial assistance programs to help defray educational costs. Nurses also need to know about tax savings that can further ease the burden of expensive continuing education. The following discussion includes a review of tax code provisions for educational deductions, several illustrative tax court cases, and the author's own experience. PMID- 8509882 TI - Automated patient acuity. Linking nursing systems and quality measurement with patient outcomes. AB - Traditional patient classification systems no longer provide a useful function for nursing management. Value from these systems can only be realized through major revisions and integration with other systems. The resulting transformed system, linking patient outcomes, cost of care, and quality measurements together, provides a valuable measurement tool and enables nursing to demonstrate their value to the industry. The authors describe their rationale and experience in designing such a system. PMID- 8509884 TI - Defining the major nursing administration issue: doing more with less. AB - "What is the major nursing administrative issue today?" The question was posed to a community of scholars in the masters program in nursing administration at the University of California, San Francisco. Using a modified nominal group approach, multiple issues were identified, explored, and prioritized. There was consensus that "doing more with less" is the most important issue and greatest of challenges. To explore this issue in depth, books relating to the topic were identified, read, and applied to nursing administrative practice. Before discussion, administrative briefings were written and distributed among the group. Previous readings and experience also contributed to the synthesis of ideas over the academic year, and the subsequent development of the following position paper. PMID- 8509885 TI - Valuing the community benefits provided by nonprofit hospitals. AB - Nurse executives need to be aware of the changing legislative climate in which nonprofit hospitals operate. Adopting an aggressive stance to protect an institution's tax-exempt status has become increasingly important. One way to provide protection from governmental challenges is to demonstrate the extent of charitable benefits provided by the hospital. The authors identify areas that hospital personnel should analyze to determine the nature and value of these benefits. Nurse executives are a valuable resource for identifying and communicating this information. They can also exert influence on their respective administrations to reassert the charitable nature of their mission. PMID- 8509883 TI - Competence, criteria, and credentialing. AB - Nurse executives, administrators, and managers are constantly being challenged by the changes in healthcare. Although it sometimes seems there is really nothing new, proactive visionary nurse administrators can rediscover, redesign, and redirect their own and others' activities to achieve organizational effectiveness. Such approaches require periodic examination of all strategies and practices--past, present, and future--for their relevance, practicality, and success. The editors of "Executive Development" reflect on topics important to organizational life. PMID- 8509886 TI - An analysis of job morale factors of community health nurses who report a low turnover rate. The research. AB - Nurse executives are continually faced with issues related to nursing turnover and staff morale. This sample included 217 registered nurses working in a state health department where the turnover rate was 8%. In this study, the authors found that nurses with advanced educational preparation, higher-level positions, or both, demonstrated increased levels of morale. Conversely, nurses with increased years of service and nursing experience had lower morale levels. These findings could be useful in delineating situations to improve morale and lower turnover rates. PMID- 8509887 TI - Implementing modular nursing in a long-term care facility. AB - Nurse administrators in long-term care are challenged to maintain the quality of nursing care under constant fiscal and staffing pressures. Restructuring nursing care delivery is one method often used to meet this challenge. The authors describe their experience of implementing a nursing care delivery model that resulted in improved continuity of care, accountability for client outcomes, and the effective use of different staff levels. PMID- 8509888 TI - Institutionalizing patient education programs. AB - Some of the best health promotion and education programs have been shortlived. This is such a common occurrence that eventually almost all nursing administrators experience the frustration of watching a good and promising program die prematurely. The authors compare and contrast two similar foot care and education programs based in Department of Veteran Affairs (VA) Medical Centers and discuss those components of planning and development that led to the long-term survival, or "institutionalization," of one of the programs. Elements of a checklist for assessing and promoting institutionalization are also presented. PMID- 8509889 TI - Recruiting and retaining registered nurses in home healthcare. AB - This study examined a personal and professional profile of registered nurses in home care to determine the most influential factors affecting their recruitment, job satisfaction, and retention. With the cooperation of a national, for-profit home healthcare organization in 1990, the authors randomly surveyed its registered nurses, licensed practical nurses, and home health aides in two Midwestern states. Findings for 107 home care registered nurses are presented and compared with responses of licensed practical nurses and home health aides. PMID- 8509890 TI - Sociotechnical systems theory. Analysis and application for nursing administration. AB - Work and system redesign are national trends in service organizations, especially healthcare. The sociotechnical systems theory of organizational design provides a framework for structure and evaluation of work redesign. Sociotechnical systems theory has recently been the framework for several innovations in the redesign of patient care. The author presents a description and analysis of sociotechnical systems theory for use in nursing administration with illustrations from research and practice. PMID- 8509891 TI - Let our voices build, not destroy. PMID- 8509892 TI - The link between continuous quality improvement and case management. AB - During the past several years, the continuous quality improvement (CQI) process has gradually been adapted to the healthcare setting to improve quality without increasing costs. In traditional quality assurance models, quality is measured by the number of accidents or errors occurring. No provision is made for improving the conditions under which the errors occurred. However, continuous quality improvement focuses on the processes used to achieve a goal. These processes may be clinical, financial, or operational issues. Each step in the process is analyzed; then a plan for improvement is tested and refined. The concepts of quality improvement that have been applied in the industrial setting are now being applied in the healthcare arena. Case management and CQI are linked in philosophy and process. The steps of the CQI process can be applied to managed care plans from both a clinical and financial perspective. PMID- 8509893 TI - A closer look at nurse retention. PMID- 8509894 TI - Accessing literature. PMID- 8509895 TI - The social climate of work environments. PMID- 8509896 TI - L-gulono-gamma-lactone oxidase is not induced in rats by xenobiotics stimulating L-ascorbic acid biosynthesis. AB - L-Ascorbic acid (AsA) is synthesized from D-glucose in rats; the terminal step of this synthetic pathway is catalyzed by L-gulono-gamma-lactone oxidase (GLO). In this study, we examined the effects of phenobarbital (PB) and 3 methylcholanthrene (MC), both of which are known to stimulate AsA biosynthesis in rats, on the hepatic levels of GLO activity, GLO mRNA, and AsA. Firstly, the existence of GLO mRNA was examined in the liver, kidney, lung, small intestine, spleen, testis, and prostate from a male rat; and GLO mRNA was found to be present only in the liver, in which GLO activity was also detected. The intraperitoneal injection with PB (100 mg/day/kg body weight, once a day for 2 days) or MC (20 mg/day/kg body weight, once) significantly elevated the hepatic level of AsA and the urinary excretion of AsA in rats (5-week-old males). The hepatic levels of cytochrome P-450IIB1 mRNA and cytochrome P-450IIB2 mRNA and those of cytochrome P-450IA1 mRNA and cytochrome P-450IA2 mRNA were also elevated in the rats treated with PB and MC, respectively, indicating a normal response of these animals to these compounds. However, the level of GLO mRNA and the activity of GLO in the liver tended to be slightly decreased by the administration of PB or MC, though the differences were not significant. Thus it is clear that the treatment with PB or MC stimulates the biosynthesis of AsA by increasing the activity of some enzyme(s) participating in the synthesis prior to GLO. PMID- 8509897 TI - Effects of restricted feeding on the absorption, metabolism, and accumulation of pentachlorobenzene in rats. AB - To investigate the effect of restricted feeding (RF) on the absorption, metabolism, and accumulation of pentachlorobenzene (PECB), rats were fed either ad libitum (AD) or a restricted diet (at 25 or 50% of AD) for 15 days. On the 7th day (day 0), PECB (15 mg/rat) was orally administered. Daily fecal weight and the total amount of PECB excreted into feces were decreased by RF, indicating an increase in PECB absorption due to its prolonged retention in the gastrointestinal tract. However, the amount of PECB excreted was only 4.8% of the dose given to the AD group, and 2.1 and 2.4% of that given to the 50 and 25% restricted diet groups, respectively. The concentrations of PECB and pentachlorophenol, and major metabolite, in blood of the restricted diet groups were higher on day 2 and day 4, while lower on day 6 and day 8 than those of the AD group. On day 8, PECB in liver, kidney, brain, and fat tissue were also lower in the restricted diet groups; the PECB levels in such tissue in the 25 and 50% restricted diet groups were 10-40 and 5-11% of that in the AD group, respectively. These results indicate that PECB metabolism was increased by RF. As PECB is lipophilic, it is most likely that the fat tissue mass, which was markedly decreased by RF, contributed to the enhancement of PECB metabolism. The mechanism seemed to be as follows: as fat tissue mass accumulating PECB decreased, the concentration of PECB in the liver increased, thus the amount of PECB metabolites formed was increased. PMID- 8509898 TI - Recovery of the ultrastructure of jejunal absorptive cells and absorption of nutrients in starved then re-fed rats. AB - This study tried to find what fat level of diets would have a good effect on recovery of the ultrastructure and the digestion-absorption function of jejunal absorptive cells in rats which had been subjected to starvation. Fat-free, 5% fat, 10% fat, or 20% fat diet was given for 3 days to the starved rats, and changes in the ultrastructure of the jejunal absorptive cells were observed by transmission electron microscopy. Also, glucose and triolein absorption were studied using an in situ perfusion system. Good recovery of the ultrastructure of jejunal absorptive cells was observed in rats re-fed the 5% fat diet. Glucose absorption did not differ among the groups except in rats given the 20% fat diet. However, triolein absorption in this group was lower than that of the other groups in both the upper and lower jejunum. The best fat level for recovery of the ultrastructure and absorption of glucose and triolein in the jejunal absorptive cells was concluded to be the 5% fat diet. PMID- 8509899 TI - Diurnal variation of plasma minerals and trace elements in a group of Japanese male adults. AB - When the nutritional status of minerals and essential trace elements is assessed by their levels in plasma, intra-individual variation in the measured values, particularly diurnal variation, must be considered. In this paper, concentrations of nine elements (Na, Mg, P, K, Ca, Fe, Cu, Zn, and Se) in plasma collected 7 times in a 24-h period from 10 healthy Japanese adults were measured with hemoglobin and plasma concentrations of proteins (total protein, albumin, retinol binding protein (RBP), ceruloplasmin, and transferrin), total cholesterol, and cortisol. Then the pattern of diurnal variation in, and the interrelationships among, these parameters were clarified in subjects who consumed an ordinary meal. Significant diurnal variation examined by two-way analysis of variance (variations due to subject and sampling time) was found for Zn, RBP, and cortisol. Plasma Zn level was higher in the forenoon samples than in those taken in the afternoon. The pattern of diurnal variation found for cortisol was similar to, but slightly different from, that for Zn. The correlation coefficient between Zn and cortisol was significant (r = 0.555) using the standardized values for individuals, and in the result of multiple regression analysis, cortisol level was selected as the significant explanatory factor for Zn variation; however, the sampling time was the most significant factor. For other elements besides Zn, no significant diurnal variation was found. Moreover, no meaningful factors were selected for variations of those elements in the result of multiple regression analysis. These results indicate that, in assessing Zn nutriture with its plasma levels, it is necessary to unify the sampling time. PMID- 8509900 TI - The use of nitrogen-15 labeling for the assessment of leguminous protein digestibility. AB - This study evaluated the digestibility of leguminous protein labeled with 15N, by using nitrogen balance and quantitation of fecal endogenous nitrogen (FEN), determined by isotopic dilution, in order to correct apparent values. Seeds of common beans, cowpea and common pea labeled with 1.000 atoms% of 15N-excess were used as protein sources in diets for 60 male Wistar rats, during a 6-day assay. The real digestibility values obtained with FEN were 77.6, 84.4, and 86.3% for common beans, cowpea and common pea, respectively. They were higher and statistically different (p < 0.05) than true digestibility values, corrected by non-protein diet. FEN showed a direct, moderate and positive relation with weight of dry matter eaten, initial body weight, weight gain and weight of dry matter of feces, the latter showing the highest correlation, with a coefficient r = 0.8930 at 1% level. PMID- 8509901 TI - Effects of amino acids on alcohol intake in stroke-prone spontaneously hypertensive rats. AB - Examination was made of the effects of amino acids on alcohol intake in stroke prone spontaneously hypertensive rats (SHRSP). The animals were divided into two groups according to dietary protein level, normal (15%) and low (5%). The two groups were further divided into two groups according to whether they selected the ethanol solution containing amino acids (non-amino acid group and amino acid group). The 5% ethanol solutions with and without various amino acids were prepared in a water-supplying tube to which the animals had free access for 40 days. The 5% ethanol solution intake in rats fed the normal protein diet was higher than that of the low protein group. Regardless of dietary protein level, 5% ethanol solution intake increased in the amino acid group. Intake of the 5% ethanol solution containing 100 mM L-proline, 100 mM L-lysine, and 100 mM L threonine was large. For the amino acid group of rats fed normal protein and low protein, plasma glutamate oxalacetate transaminase (GOT) activity was significantly reduced. It is suggested that the alcohol intake may increase by adding amino acid to the alcohol solution. PMID- 8509902 TI - The effect of various phospholipids on plasma lipoproteins and liver lipids in hypercholesterolemic rats. AB - Rats were fed a hypercholesterolemic diet (5% lard, 0.5% cholesterol, and 0.25% sodium cholate) containing 5% of dietary phospholipid as safflower phospholipid (SAP), soybean phospholipid (SOP), or egg yolk phospholipid (EGP), or 5% of soybean oil (SO) as a control for 4 weeks. The concentrations of plasma cholesterol were significantly higher in rats fed the EGP diet than those of the other diets. Similarly, the concentrations of chylomicron plus very low density lipoprotein (VLDL) cholesterol were higher in rats fed the EGP diet. The phospholipid diets induced a significant increase of high density lipoprotein (HDL) cholesterol in comparison with the SO diet. The concentrations of liver cholesterol were significantly lower in rats fed the phospholipid diets than those of the SO diet. Among phospholipid-fed rats, the SAP and SOP diets decreased the concentrations of liver cholesterol compared with the EGP diet. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was significantly increased in rats fed the phospholipid diets. The phospholipid diets caused an enhanced excretion of neutral steroids into feces. Among phospholipid-fed rats, the SAP and SOP diets increased the excretion of fecal neutral steroids compared with the EGP diet. The fatty acid composition of HDL phospholipid was slightly reflected by the major dietary fat source. These results suggest that SAP and SOP inhibit markedly the absorption of dietary cholesterol in the small intestine of hypercholesterolemic rats and that the effect of SAP and SOP on plasma cholesterol metabolism may be different from that of EGP. PMID- 8509903 TI - Services for impaired nursing practice: report of a survey. PMID- 8509905 TI - Annotated bibliography: selected statistical resources on health care topics. PMID- 8509904 TI - The literature review. PMID- 8509906 TI - From research project, presentation, or clinical innovation to publication: what reviewers look for. PMID- 8509907 TI - Preparing research results for journal submissions. AB - This article provides a summary of the important factors to consider in preparing a research manuscript for submission to The Journal of the New York State Nurses Association. Sharing research results in a professional journal can be both a demanding and exciting process. Researchers are encouraged to apply the rigor associated with research design and methods to pen and paper when preparing manuscripts for publication. Following the guidelines for outlining a research article, editorial style, and manuscript preparation will help researchers succeed in publishing a good piece of research. PMID- 8509908 TI - Strategic technology acquisition management. AB - Each day, as operating margins continue to shrink, hospitals are confronted with extremely difficult technology acquisition decisions. They seek to ensure that their technology purchases address issues of safety, clinical efficacy, and cost benefit. This paper proposes a structure for developing a strategic technology acquisition plan and identifies the role of nurses and their health care counterparts in the process. PMID- 8509909 TI - Helping to prevent domestic violence. PMID- 8509910 TI - Diagnosis and treatment of fractures of the facial bones in children 1943-1993. AB - It is clear that the foundations for diagnosis and the basic principles of management have changed little since 1943 and probably since the work of Kazanjian in World War I. Major advances have occurred, with modern techniques of airway management (particularly fiberoptic laryngoscopy), anesthesia, and an understanding of fluid and electrolyte balance and behavioral issues in children. In addition, the advent of antibiotics; new imaging techniques (particularly CT), and availability of new instrumentation and rigid internal fixation have all revolutionized the specific treatment of pediatric facial fractures. Craniofacial techniques, pioneered by Dr Paul Tessler, have significantly altered and improved treatment of pediatric midface fractures. Progress in the biology of bone healing will surely mark the next 50 years. PMID- 8509911 TI - Occlusal plane alteration in orthognathic surgery. AB - This article discusses correction of functional and esthetic deformities by surgically increasing or decreasing the occlusal plane angulation. Clockwise rotation, or increase of the occlusal plane angulation, is a well-accepted technique in orthognathic surgery. However, counterclockwise rotation (decrease of the occlusal plane angulation), has not been a well-accepted treatment approach. The functional and esthetic characteristics of the low occlusal plane and the high occlusal plane facial types are presented, specific surgical approaches to alteration of the occlusal plane are described, and the long-term stability of results with both clockwise and counterclockwise rotations of the occlusal plane are discussed. Cases illustrating the application of these surgical approaches are presented. PMID- 8509912 TI - Obstructive sleep apnea syndrome: a surgical protocol for dynamic upper airway reconstruction. AB - A surgical protocol for dynamic upper airway reconstruction in the treatment of obstructive sleep apnea syndrome is presented. Two hundred thirty-nine consecutively treated patients were evaluated. All patients underwent a presurgical evaluation that included a physical examination, fiberoptic pharyngoscopy, cephalometric analysis, and polygraphic monitoring. The goal of the presurgical evaluation was to document sleep apnea and isolate the area of obstruction. The treatment was then directed to the obstructive site. The surgical protocol included two phases. Phase 1 was a conservative approach and included uvulopalatopharyngoplasty and/or mandibular osteotomy with genioglossus advancement-hyoid myotomy and suspension. Polysomnography was repeated at 6 months and patients with unsuccessful surgical results were offered maxillary mandibular advancement osteotomy. Results were based on the postoperative polysomnograms, and included assessing changes in both sleep architecture and sleep-disordered breathing. The surgical results were compared with results in patients who were using nasal continuous positive airway pressure. The surgical success rate for the 239 patients entered into phase 1 therapy was 61% (145 patients). Twenty-four patients who failed phase 1 treatment elected phase 2 treatment. The surgical success rate of this phase was 100%. PMID- 8509913 TI - Dosage effects of pulsed steroid therapy on serum cortisol levels in oral and maxillofacial surgery patients. AB - The purpose of this study was to determine the effects of two dosage regimens of dexamethasone on the serum cortisol levels of a group of patients undergoing major maxillofacial surgical procedures. Analysis of the data demonstrated that the use of dexamethasone, 10 to 20 mg intravenously given every 3 hours intraoperatively and every 4 hours postoperatively over 24 hours, followed by a repository dose of 80 mg of intramuscular methylprednisolone, causes short-term serum cortisol suppression. The maximum depression occurred on postoperative day 3; normal levels were restored by postoperative day 7. Therefore, pulsed therapy can be considered relatively safe when known contraindications have been considered. PMID- 8509914 TI - Combined transmandibular-zygomatic approach and infratemporal craniotomy for intracranial skull base tumors. AB - Large intracranial skull base tumors remain surgically treacherous lesions. The preauricular transzygomatic infratemporal approach to this area has rapidly gained popularity. This article presents modifications to this approach which improved visualization and access to the infratemporal fossa. The procedure increases visualization, minimizes brain retraction, and results in improved resection and outcome. Reconstruction is rapid and there are minimal functional and cosmetic deficits. PMID- 8509915 TI - Treatment of melanotic spots in the gingiva by argon laser. AB - Dark colored areas, ranging from light blue to black, often occur in the gingiva as a result of the abnormal deposition of melanin. These can develop at any age, creating an unesthetic appearance. The effective elimination of these melanotic areas can be accomplished by treatment with monoline 514 nm green light (1.5 W, 300 milliseconds, 0.5-mm spot size) produced by an argon laser. Restoration of the mucosa is optimal, giving excellent esthetic results. PMID- 8509917 TI - A comparison between the clinical behavior of neurilemmomas in the neck and oral and maxillofacial region. AB - The records of 49 patients with neurilemmoma in the neck and oral and maxillofacial region (OMR) were reviewed. The results showed some location related differences in clinical behavior, including six cases of recurrence and two cases of malignant change found in the OMR. It was suggested that anatomic factors play an important role in the poor prognosis of tumors in the OMR. PMID- 8509916 TI - Dental follicular tissue: misinterpretation as odontogenic tumors. AB - The dental follicle is radiographically and histologically observed in association with unerupted or impacted teeth. However, this normal tissue structure is often confused with odontogenic tumors by pathologists with limited experience in evaluating jaw lesions. This study was designed to evaluate the incidence and possible reasons for incorrect interpretation of dental follicles. From 1970 to 1988, 847 dental follicles and/or dental papillas from 663 patients were submitted to the Armed Forces Institute of Pathology (AFIP) by medical pathologists seeking diagnostic consultation. Nearly 84% of patients were in the second and third decades of life. The male to female ratio was 1.4:1.0. Over 70% of specimens were obtained from around impacted third molar teeth. Fifty-three percent of specimens were correctly interpreted by the contributing pathologists. Only a descriptive interpretation was given for 17%, no diagnosis was made in 10%, and 20% were incorrectly diagnosed. In descending order, the most frequent incorrect diagnoses were odontogenic cyst, odontogenic myxoma, odontogenic fibroma, ameloblastic fibroma, odontoma, and ameloblastoma. Dental papillas were most frequently misdiagnosed as odontogenic myxomas. The histologic features and diagnostic pitfalls are discussed, as well as the need to consider the clinical, radiographic, and microscopic features in arriving at a final diagnosis. PMID- 8509918 TI - The embryologic development of the human lateral pterygoid muscle and its relationships with the temporomandibular joint disc and Meckel's cartilage. AB - The morphology of the developing lateral pterygoid muscle and its relationships with the temporomandibular joint disc and Meckel's cartilage were studied in 16 human embryos and fetuses ranging in age from 5 weeks to 14 weeks. All the temporomandibular joint structures and the lateral pterygoid muscle assumed their adult shapes by the 14th week of fetal life. At this stage, the lateral pterygoid muscle is a complex structure with several aponeuroses dividing the muscle into three main parts: superior, inferomedial, and inferoanterior. The superior part is attached to the disc superiorly and medially. The inferomedial part inserts into the anteromedial aspect of the condyle and disc. The inferoanterior portion is attached to the anterior aspect of the condyle. Anteriorly, the buccal nerve and associating blood vessels traverse the muscle in a mediolateral direction, dividing it into superior (small) and inferior (large) compartments. Posteriorly, the muscle remains intact with no separation. The lateral pterygoid muscle fibers show no direct attachment to Meckel's cartilage at any stage of development. PMID- 8509919 TI - Diagnosis and treatment of retrobulbar hemorrhage. AB - Complete loss of light perception in an eye is one of the most severe complications of maxillofacial surgery. Although irreversible in many cases, early recognition and prompt intervention may improve the final outcome. The purpose of this article is to review the etiology and pathophysiology of retrobulbar hemorrhage, and discuss its diagnosis and management. PMID- 8509920 TI - Simultaneous masses of the palate and body of mandible. PMID- 8509921 TI - Coincidental sublingual and submental epidermoid cysts. PMID- 8509922 TI - Concomitant sublingual and submental epidermoid cysts: a case report. PMID- 8509923 TI - Adenocarcinoma of the colon metastatic to the temporomandibular joint: a case report. PMID- 8509924 TI - Squamous cell carcinoma mimicking median rhomboid glossitis region: report of a case. PMID- 8509925 TI - Condylar fracture with unusual displacement: a case report. PMID- 8509926 TI - Maxillary obturator supported by osseointegrated implants placed in irradiated bone: report of cases. PMID- 8509927 TI - Fibrous defect of the mandible: a case report and literature review. PMID- 8509928 TI - A technique for accurate long-term follow-up of segment positional changes following sagittal split osteotomies. PMID- 8509929 TI - Early treatment of orbital floor fractures. PMID- 8509930 TI - Cautions in the use of postauricular skin grafts. PMID- 8509931 TI - Interpretation of disc-condyle relationships after modified condylotomy. PMID- 8509932 TI - [Studies on the generation mechanism of non-biological response in distortion product OTO-acoustic emission]. AB - We investigated the effect of non-biological artifacts on the measurement of distortion product oto-acoustic emission (DPOAE) using guinea pigs, and the generation mechanism of this phenomenon is discussed in the present paper. When a sound pressure of a stimulating tone was too large, an overtone was produced within the acoustic probe. When the difference in sound pressure between f1 and f2 was too large, artifacts appeared at frequencies of 2f1-f2 or 2f2-f1. Similar responses were generated when f1 and f2 were identical in sound pressure but exceeded a certain critical level. These non-biological responses could be easily differentiated from biological responses by subjecting the animal to anoxia. The input-output curve of DPOAE was biphasic and clearly showed this critical level in each animal. The results obtained in the present study suggest that the levels of f1 and f2 should be almost equal and should not exceed the observed critical level when measuring DPOAE. PMID- 8509933 TI - [Bone mineral density of the internal auditory meatus by quantitative computed tomography]. AB - The bone mineral density of the internal auditory meatus was investigated by means of quantitative computed tomography in 20 normal subjects (40 ears). Investigated portions of the internal auditory meatus were the porus anterior and posterior and the fundus anterior and posterior. Two other portions of the ear, the bony vestibule and lateral wall of the mastoid, were also investigated. The bone density values (calcium carbonate equivalent value) for each portion were analyzed statistically. The following results were obtained: 1) There was no significant difference between the right and left values in any portion. 2) The highest mean value was found in the fundus posterior, the lowest in the porus anterior. There was a significant difference between the values of the fundus and porus. Bone hardness generally correlates with bone density. Thus, the bone hardness of the porus of the internal auditory meatus was appraised to be lower than that of the fundus. These results suggest that this is one of the factors promoting enlargement of the internal auditory meatus in acoustic neuroma. PMID- 8509934 TI - [Studies on screening for hard-of-hearing children by questionnaire. 2. Comparison of response rates to individual questions in 1-year-6-month-old children with normal hearing and hearing loss using a health screening questionnaire]. AB - We report the results of studies on responses to questions on hearing impairment, comparing 165 school children whose hearing was diagnosed as normal at the time of admission to primary school and 37 children with hearing loss attending facilities for children with this disability. These children had been covered by similar surveys as part of the health screening for 1-year-6-month-old infants conducted by municipal authorities. Significant differences between the two groups were noted in the response rates to all questions on hearing. Similar differences were noted in the responses to questions on family history of hearing impairment. There were no significant differences in the incidences of asphyxia and jaundice at birth. The most striking differences were noted in the response rates to questions 6, 7, 8, 10, 11, 16, and 18. Most useful and universally valid in this survey were questions 8, 10 and 18 in addition to the question on whether or not parents suspected infantile hearing loss. PMID- 8509935 TI - [Acoustic rhinometry as method for evaluating paranasal sinuses--experimental studies]. AB - The potential application of acoustic rhinometry for evaluating paranasal sinuses was evaluated experimentally. In order to assess the influence of paranasal sinus volume in acoustic rhinometry, three model studies were performed. A tube made of acryle (20 cm in length, 2 cm in diameter) with a side hole was used for the first experiment. In the experiment measuring this tube with acoustic rhinometry, a difference between cases with a side hole (ex. 2 mm in diameter) and these without a side hole was observed. In the former, a more posterior tube position gave rise to an increase in the acoustic curve. In the second experiment, a syringe was was fixed to the side hole of the tube, so as that no leakage of sound wave would occur. A change in the volume of the syringe could be detected by acoustic rhinometry, even with changes as small as 1 ml. In the third experiment, the relationship between the size of the side hole and the volume of the syringe was evaluated. When the volume was less than 20 ml, the value was almost equal to the theoretical value even if the diameter of the side hole was as small as 4 mm. A larger size hole was required when the volume was increased. It was concluded that acoustic rhinometry is of possible value in assessing the paranasal sinuses, if the nasal cavity communicates with the paranasal sinuses via a large opening (e.g. in post-operative cases). PMID- 8509936 TI - [Maxillary prosthesis for better QOL--analysis of maxillary prosthesis stability]. AB - We report here an analysis of 100 cases of maxillary prosthesis, experienced from July, 1981 through June, 1989, with special reference to stability. Sixty-four percent of prostheses were partial denture type and complete denture type comprised thirty-two percent. Eighty-six percent of cases were estimated to have defects exceeding 2/6 and 3/6 of the surface width of the palate. Ninety percent of prostheses weighed less than 15 gm. The stability of these prostheses was estimated to be good in 85% of cases, the stability of the denture type being good in 95% of partial denture type cases, and 62% of complete denture type cases. According to type distinctions among maxillary defects as a whole, in the smaller 1/6 and 2/6 defect cases, good stability can be expected, and in 3/6 and 4/6 defect cases, 80% achieve good stability. According to prosthesis weight, 80% of those weighing less than 15 gm were considered to have shown good stability. Thus, these maxillary prostheses can remain in place and functional ameliorating disability and contributing to the patient's quality of life. PMID- 8509937 TI - [Relation of evoked otoacoustic emission to structural damage after acoustic overstimulation in cat]. AB - Evoked otoacoustic emissions (e-OAE) at a 2 kHz tone burst were measured in 37 ears of 21 cats. The e-OAE responses were detectable in 30 ears of 19 cats. In most cats (26 out of 30 ears) nonlinear behavior could be identified and saturated above 15 to 20 dBnHL. The responses had very short latencies (to their peak pressures) of 5.53 ms to 7.28 ms. Scanning electron microscopy (SEM) was used to examine feline cochleas for structural damage after exposure to a 2 kHz pure tone (105 dBSPL and 125 dBSPL). Following a 105dB exposure for 30 min acoustic response recovered to normal levels at 120 min after exposure with no significant loss of hair cell stereocilia. Fatigue induced changes in outer hair cell activity may be relevant to the production of TTS. The loss of stereocilia on outer hair cell row 1 and on inner hair cells was seen between 6 and 9 mm from the apex after exposure to a 125dBSPL, 2 kHz pure tone for 30 min and e-OAE disappeared after overstimulation in all these cases. We found that e-OAE was affected by minimal cochlear damage. PMID- 8509938 TI - [Abnormal adductor movement of the vocal cords in spasmodic dysphonia]. AB - Adductor movement of the vocal cords in initial/ke/phonation was recorded using a laryngeal fiberscope, CCD camera, and videocassette recorder. Three patients with adductor spasmodic dysphonia (SD), a 53 year old male and 48 and 52 year old females, and 7 normal volunteers participated in this study. During the examination, the subject sat on a chair holding a microphone about 20 cm away from his or her lips. A laryngeal fiberscope was inserted through either side of the nostril. The tip of the fiberscope was positioned just caudal to the tip of the epiglottis to get a complete view of both sides of the vocal cords. The examiner told the subject to make the speech sound/ke/repeatedly, and to insert a sufficient inspiratory period between each phonation. The vocal cord images were recorded at 30 frames per second and printed successively from several frames ahead of the beginning of adductor movement to the frame of initial adjustment of the membranous part of the vocal cords following a time code indicator. The tips of both sides of the vocal processes and anterior commissure were marked, then, scanned and transported to a personal computer. An imaginary line connecting the vocal process and anterior commissure was drawn on the screen of the computer, which was done on both sides of the vocal cords. Then, an angle made by the two lines was measured in degrees and stored. The time and speed of adductor movement varied among subjects. Normal subjects, however, never failed to finish making the explosive sound in /ke/ before initial vocal cord adjustment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509939 TI - [An embryological study of mouse ear using the whole embryo culture technique]. AB - Mouse embryos were explanted at 11.5 days of gestation and cultured for periods of 6, 12, 18, 24, 30, 36, 42 and 48 hours using the whole embryo culture system. A continuous flow of gas (5% CO2+95%O2) was maintained through the culture bottles during the culture periods. The cultured embryos were morphologically and histologically examined at the end of the designated periods. The growth of the embryos was depressed after about 36 hours, and differentiation was retarded as the culture time increased. General development had ceased almost completely by 42-48 hours. At 18-36 hours, the external auditory canal and pinna, which are not developed in 11.5 day embryos, could be observed clearly on the surface of the head. After 42 hours, the facial features including the external ear were similar to those of 13 day in vivo embryos. Serial sections of the ear region of cultured embryos showed that development of the inner and middle ear structures up to 42 hours was the same as that seen from 11.5 to 13 days in vivo. In the inner ear, the otocyst had developed into the vestibule, cochlea and semicircular canals by 12-30 hours. In the middle ear, the stapedial anlage appeared and its circular shape became clear between 0 and 12 hours. Subsequently, the medial portion of the stapedial anlage grew until it was adjacent to the developing otic capsule, and the anlages of other ossicles were also recognizable after 18 hours. Differentiation of the horizontal portion of the facial nerve was noted at the same time that stapedial anlage and otic capsule were developing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509940 TI - [Role of surface tension lowering substances in the function of normal and diseased eustachian tubes of guinea pigs]. AB - To examine the role of surface tension lowering substances (STLSs), we measured changes in passive opening pressure (OP) and closing pressure (CP) in eustachian tubes of guinea pigs before and after washing the tubes with various solutions (saline solution, artificial pulmonary surfactant, synthetic phospholipids, and detergent)). The percent decreases in OP and CP in tubes washed with artificial surfactant were significantly higher than those washed with saline solution. Those washed with synthetic phospholipids or detergent (Triton X-100) did not differ from those washed with saline solution. In guinea pigs with experimental otitis media produced by inoculation of formalin-killed Haemophilus influenzae into the middle ear cavity, the percent decreases in OP and CP in tubes washed with artificial pulmonary surfactant were significantly higher than in those washed with saline solution. Artificial pulmonary surfactant was injected into the middle ear cavity of the guinea pigs with otitis media. At 5 days after inoculation, the inflammatory changes of the middle ear were much milder in animals with intratemporal application of artificial pulmonary surfactant than in those with saline application. These results suggest the possible efficacy of treatment with artificial pulmonary surfactant for otitis media. PMID- 8509941 TI - [Facial nerve paralysis induced by herpes simplex virus infection in mice]. AB - The etiology of Bell's palsy remains unknown but clinical serological investigations have suggested herpes simplex virus (HSV) induced facial neuritis to be a potential cause. In order to verify the viral etiology of Bell's palsy it must be proved by animal experimentation. The author first succeeded in producing a transient facial paralysis of mice, with a herpes simplex viral neuritis simulating human Bell's palsy. Type 1 HSV (strain KOS, 4.5 X 10(6) pfu/ml) was inoculated into the posterior aspect of the auricle. Fifty-nine out of 104 mice (56.7%) developed facial paralysis, on the experimental side, 6 to 9 days after the inoculation. The facial paralysis continued for 3 to 7 days and resolved spontaneously. In 36.8% of the animals with facial palsy, HSV antigens were identified mainly in the geniculate ganglion cells, satellite cells, Schwann cells and nerve fibers of the involved side using immunohistochemical methods. No HSV antigen was demonstrated in the facial nerve of the contralateral side in animals with facial paralysis, bilateral facial nerves in animals without facial palsy or in control animals. Histopathologically, the involved nerve showed findings of viral neuritis such as round cell infiltration and vacuolar degeneration of nerve fibers. Inflammatory changes were noted in and around the geniculate ganglion but were more pronounced in nerve fibers proximal to the ganglion. These findings persisted for as long as a month after normal facial function had been restored.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509942 TI - Rapid and simple method for measurement of the cholesterol content of gallstones. PMID- 8509943 TI - Immunologic significance of increased soluble CD8/CD4 molecules in patients with active systemic lupus erythematosus. AB - This study attempted to estimate soluble CD4(sCD4)/CD8(sCD8) molecules in active systemic lupus erythematosus (SLE) patients. Measurements were made by solid phase enzyme-linked immunosorbent assay. sCD8 or sCD4 molecules were significantly increased in the patients as compared to control subjects. sCD8 correlated with the erythrocyte sedimentation rate. sCD4 correlated with the anti DNA antibody titer, the IgG concentration, and negatively with the complement titer. An association of these molecules with immunologic abnormalities and disease activity exists in SLE patients. PMID- 8509944 TI - A survey of ciguatera: assessment of Puako, Hawaii, associated with ciguatera toxin epidemics in humans. AB - A survey for the assessment of the ciguatera problem has been determined in Puako, South Kohala, on the Island of Hawaii. This is in the area of persistent ciguateric outbreaks during the months of January through March, caused by a specific species of fish (Cheilinus rhodochrous, red rose wrasse, or po'ou). Analyses of algae, Gambierdiscus toxicus, and various species of fish, including herbivores and carnivores, gave positive indications of Puako as a potential ciguateric area. Algae associated with Gambierdiscus toxicus blooms and the dinoflagellate itself were found in transects A and D. Transects A and D showed 291 G. toxicus per gram of Tolycarpidia glomurata and 9 G. toxicus per gram of Turbinaria sp. with epiphytic Jania sp., respectively. No G. toxicus was found in transects B and C. This may be attributed to the low salinity from intrusion of freshwater in this vicinity. Examinations of the fish, kole, manini, Hawaiian kole, roi, and po'ou by the solid-phase immunoassay showed 89% of fish in the borderline and positive categories from all transects. Extracts of viscera and flesh showed high levels of toxicity in mouse (13 of 23 deaths), particularly in the viscera (gut) of both herbivores and carnivores. The guinea pig atrial analysis generally showed a few ciguatoxin-like, but most were nonciguateric type responses. The data presented in this Puako survey showed evidence of toxic fish associated with ciguatoxin-like and most probably other toxins, either polyethers or non-polyethers as yet unidentified. PMID- 8509945 TI - Study of the susceptibility of human colorectal tumor explants to LAK-cell lysis: comparison of various cytotoxicity tests. AB - The susceptibility of tumor cells from cultures of 8 human colorectal tumor explants to a standard LAK preparation originating from a single healthy donor was assessed in 5 various cytotoxic tests. Target cells were suspended or attached (in three different 51Cr-release 4 hr tests), grown as a confluent monolayer (in a colorimetric 72 hr test) and grown as three-dimensional spheroids (in a 51Cr-release 24 hr assay). The susceptibility to lysis observed for one tumor in the 5 tests varied from 4 to 15 times and was a tumor attribute independent of the susceptibility to lymphocyte attack. There was no correlation of results between the 4 hr tests and a 72 hr test performed on monolayer, or the spheroid test taking into account the resistance of the three-dimensional structure to lymphocyte invasion. Our study excludes the possibility of quantitative interpolation of assessments of tumor cell susceptibility to lymphocytes received from various tests. It also refers to simple reductionist tests which may be compared, however, after ranking the qualitative categories. PMID- 8509946 TI - Evaluation of nonisotopic labeling and detection techniques for nucleic acid hybridization. AB - We have used a double-stranded DNA probe linked to the cystic fibrosis locus to detect a single-copy gene from varying amounts of genomic DNA, with Southern blot analysis. The DNA plasmid probe was labeled with either biotin or digoxigenin. Biotin or digoxigenin was then linked to alkaline phosphatase (ALP) with use of streptavidin or anti-digoxigenin antibodies, respectively. ALP activity was then detected with a chromogenic (BCIP/NBT), chemiluminogenic (AMPPD), or fluorogenic (HNPP) substrate. Our results suggest that biotin and digoxigenin perform similarly and that the three substrates exhibit similar detectability under appropriate substrate incubation times: 20-120 min (AMPPD), 2-12 h (HNPP), and 18 48 h (BCIP/NBT). Under optimised conditions and the probe used, these methods detect single-copy genes from as little as 0.3 micrograms of total genomic DNA. PMID- 8509947 TI - Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjogren's syndrome. AB - We attempted to determine whether cell adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin (endothelial-leukocyte adhesion molecule-1; ELAM-1), are involved in the lymphoid cell infiltration of the salivary and lacrimal glands in Sjogren's syndrome (SS) patients. Both immunohistochemical analysis and the reverse-transcripts polymerase chain reaction (RT-PCR) were used to analyze the expression of VCAM-1, ICAM-1, ELAM-1, very late antigen 4 (VLA-4 [alpha 4,beta 1]), lymphocyte function-associated antigen-1 (LFA-1), interferon-gamma (IFN gamma), tumor necrosis factor (TNF), and interleukin-1 beta (IL-1 beta). Immunohistochemical analysis of salivary gland biopsies from SS patients showed a marked expression of VCAM-1 and ICAM-1 in the venules surrounded by infiltrated CD4+ CD45RO+ T cells. E-selectin was expressed on vascular endothelium with weak intensity. Increased levels of VCAM-1, ICAM-1, IFN-gamma, and IL-1 beta mRNA were demonstrated by RT-PCR, whereas E-selectin mRNA were weakly expressed in SS lacrimal and salivary gland tissues. This is in contrast with strong expression of ELAM-1 in IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) in vitro. Cytokine-mediated up-regulation of VCAM-1 and ICAM-1 that facilitates the recruitment of VLA-4 and LFA-1 expressing T cells might contribute to lymphoid cell infiltration in the salivary and lacrimal glands in SS. PMID- 8509948 TI - Defective phagocytosis in chronic trichophytosis. AB - Chronic trichophytosis as a primary clinical entity (primary chronic trichophytosis, PCT) is increasingly encountered in the literature. Its prevalent cause in Croatia is the anthropophilic form of Trichophyton interdigitale. Chronicity of the disease may result from immunological defects of the patients. Thus, in 62 patients with PCT: skin testing, enumeration of T- and B-lymphocytes in the peripheral blood, quantitation of immunoglobulin classes, and phagocytosis (random mobility, ingestion, digestion and extracellular killing) by peripheral blood leukocytes was tested. The findings were compared to those in healthy persons. Defective phagocytosis (random mobility, ingestion and digestion) was found in patients with PCT (P < 0.001). All the other results were within the control range. Therefore, PCT seems to be associated with defective phagocytosis of peripheral blood leukocytes in affected persons. PMID- 8509949 TI - Humoral and cellular immune responses to Microsporum canis in naturally occurring feline dermatophytosis. AB - Peripheral blood lymphocytes isolated from cattery cats which were culture positive for Microsporum canis, or from cats which had recovered from M. canis infection, showed a significantly greater mean in vitro blastogenic response to M. canis antigen than lymphocytes from uninfected cats. Mean lymphocyte reactivity to concanavalin A was higher in cats which had recovered from infection than in either culture positive or uninfected cats, whereas reactivity to phytohemagglutinin was highest in the culture positive group. Antibody (both IgG and IgM) against dermatophyte glycoprotein antigen was detectable in the plasma of all cats, but was present in significantly higher titres in the culture positive group. Our results demonstrate that M. canis infected cats mount strong humoral and cellular immune responses to the organism; these responses can be detected by use of anti-dermatophyte antibody quantitation and lymphocyte blastogenesis assays, as has been reported previously for dermatophytosis in other species. Asymptomatic, culture positive cats were found in only three of seven catteries and were genetically related, raising the possibility of genetic predisposition to persisting asymptomatic infection. PMID- 8509950 TI - Effect of ajoene on dimorphism of Paracoccidioides brasiliensis. AB - Ajoene, a compound derived from ethanolic garlic extracts, inhibits the growth of the dimorphic pathogenic fungus Paracoccidioides brasiliensis, yeast cells being more sensitive to its action than mycelial cultures. Sulphydryl protector groups were able to cancel the inhibitory effect on the yeast cells but not on the mycelial cultures. The dimorphic process was also blocked when mycelia were placed to transform to yeast. Synthesis in vitro of cell wall glucan was not affected by ajoene. We discuss the possible involvement of ajoene on sulphydryl metabolism of P. brasiliensis. PMID- 8509951 TI - Mucosal and disseminated candidiasis in gnotobiotic SCID mice. AB - The alimentary tracts of germ-free SCID (severe combined immunodeficient) mice were susceptible to colonization with Candida albicans. Large viable populations (10(6)-10(8) colony forming units g-1) of C. albicans, in pure culture, were present in all sections of the intestinal tract. Candida-colonized SCID mice, sacrificed at various time intervals over a 16 week study, manifested chronic superficial mucosal candidiasis of keratinized epithelial surfaces (tongue and stomach). Despite the continuous presence of large viable populations of C. albicans in their intestinal tract, only superficial mucosal candidiasis and no progressive disseminated candidiasis of endogenous origin was evident in these mice. Treatment with cyclophosphamide (100 mg kg-1, intraperitoneally) enhanced the susceptibility of SCID mice to mucosal (tongue and stomach) candidiasis. Gnotobiotic (C. albicans-colonized) SCID mice were also found to be as resistant as immunocompetent BALB/c mice to acute (intravenous challenge) renal candidiasis. Colonization of the alimentary tract with a bacterial flora appeared to enhance the resistance of SCID mice to disseminated candidiasis. This study demonstrates that innate immune mechanisms (phagocytic and/or NK cells), in the absence of functional T- and B-cells, play an important role in the resistance of SCID mice to mucosal and disseminated candidiasis of endogenous (intestinal tract) or acute (intravenous challenge) origin. PMID- 8509952 TI - Diagnosis of paracoccidioidomycosis by passive haemagglutination assay of antibody using a purified and specific antigen-gp43. AB - Sheep red blood cells, treated with glutaraldehyde and sensitized with a purified Paracoccidioides brasiliensis antigen of molecular mass 43 kDa (gp43), were used to detect antibodies to P. brasiliensis by passive haemagglutination (PHA). Sera from 50 patients with paracoccidioidomycosis had PHA titres of > 1/800, and had antibodies detectable by immunodiffusion while antibodies to gp43 were detectable by PHA in sera from patients with histoplasmosis, aspergillosis, candidiasis, Jorge Lobo's disease or healthy people, only at titres of < 1/100. Considering a cut-off at 1/200, the sensitivity and specificity of PHA for paracoccidioidomycosis was 100%. Thus, the PHA test could be an efficacious method for routine serological diagnosis of paracoccidioidomycosis, with results in 1 to 2 h. PMID- 8509953 TI - Cryptococcus neoformans var. gattii in India. AB - An examination of 18 clinical isolates of Cryptococcus neoformans from India revealed that 15 belonged to C. neoformans var. neoformans (serotype A = 13 isolates, serotype AD = two isolates) and three belonged to C. neoformans var. gattii (serotype B). This is the first documented record of the var. gattii and serotype AD of the var. neoformans occurring in India. PMID- 8509954 TI - Uncommon invasive fungal pathogens in the acquired immunodeficiency syndrome. AB - This communication lists fungi reported to cause invasive infection in patients with AIDS. It excludes the well known and common fungi that infect these patients such as Candida, Cryptococcus, Histoplasma, Coccidioides and Aspergillus. It is likely that these less common fungal pathogens will be seen more frequently in the enlarging AIDS population as it is continuously exposed to many of these potentially opportunistic fungi. PMID- 8509955 TI - Paracoccidioidomycosis and its etiologic agent Paracoccidioides brasiliensis. AB - Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, a systemic mycosis endemic to Latin America. In this paper we review clinical, therapeutic and immunological aspects of the disease, as well as the biology and ecology of the fungus, restricting the review to the period 1989-1992. PMID- 8509956 TI - Nurse practitioners: effective providers of primary care. PMID- 8509957 TI - Respite care for families of children with disabilities. AB - The number of children with chronic health problems and resultant disabilities is increasing. Most of the care received by these children is provided by family members, often at severe economic and psychologic cost. One service that has appeared in the past two decades to assist family caregivers is respite services. This article describes the needs for respite identified by family members, the types of respite services available, the benefits of respite care to families, and the essential roles nurses can assume in assuring this essential service is available to families. PMID- 8509958 TI - Teaching families to evaluate age-appropriate toys. AB - Nurses should stress to parents that they need not purchase the most frequently advertised or expensive toy to promote their child's growth and development skills. As parents develop an understanding of normal growth and development and how to evaluate and stimulate their child's development through the use of toys, they will be able to select and create appropriate toys that will not frustrate or overstimulate the child. This approach will enable all parents, regardless of income, education, and resourcefulness, to promote and stimulate their child's gross and fine motor skills, social development, and cognitive development through the use of toys. PMID- 8509959 TI - Using a comprehensive taxonomy of diagnoses to describe the practice of pediatric nurse practitioners: findings of a field study. AB - The goal of this study was to develop and field test a classification of diagnoses for use by pediatric nurse practitioners. A secondary goal was to describe the clinical practice of pediatric nurse practitioners in a way using a classification that integrates medical, nursing, and developmental diagnoses. Six pediatric nurse practitioners were oriented to the system, established interrater reliability, and then used the system to record their diagnoses for 240 consecutive patients each. The pediatric nurse practitioners used more than 3000 diagnoses with 1450 cases. Their scope of practice included 1% developmental problems, 72% pediatric diseases, which included 51% illnesses and 21% disease prevention and screening, and 27% daily living problems. Pediatric nurse practitioner coders evaluated the system in positive terms. Issues related to the use of a taxonomy such as this one for practicing clinicians were discussed. PMID- 8509960 TI - Diagnostic clues in treating children with superficial fungal infections of the skin. PMID- 8509961 TI - Nightmares. PMID- 8509962 TI - Childhood immunization--Part II. PMID- 8509963 TI - Overuse knee injuries. PMID- 8509964 TI - The Clinical Laboratory Improvement Amendments of 1988--what they mean to pediatric nurse practitioners. PMID- 8509965 TI - The pediatric nurse practitioner on call. PMID- 8509966 TI - Poison prevention. PMID- 8509967 TI - Third-party payor billing and reimbursement for nursing services: infant apnea management. AB - This article examines the process of implementing a program for billing third party payors for the services of the pediatric clinical nurse specialist. Factors to consider when initiating a billing program are discussed, as well as guidelines for structuring the charges, obstacles to reimbursement and strategies to overcome them, and benefits (both direct and indirect) of implementing such a program. Examples are cited from apnea management programs at two major children's hospitals in the southwestern United States. Implications are made regarding generalizing these methods to other nursing services and practices. PMID- 8509968 TI - Behavioral contracting to improve adherence in patients with thalassemia. AB - Twenty-three patients with thalassemia contracted to improve their adherence with subcutaneous desferrioxamine by increasing their number of days of use. Adherence, as measured by empty vial counts, was positively reinforced by careful monitoring and behavioral reward system. Contingency contracting was successful in 76% of patients over a 6-month period, with 69% maintaining improvement in adherence 2 months after the program. Findings supported the efficacy of behavioral intervention strategies in the care of patients with chronic illness. PMID- 8509969 TI - Physical activity and exercise in children with cystic fibrosis. AB - The purpose of this study was to describe both the level and relationship of physical activity and exercise in children with cystic fibrosis of varying degrees of severity. Thirty-six children (19 girls and 17 boys) between 6 and 19 years of age with cystic fibrosis underwent pulmonary function and graded treadmill testing. Physical activity was measured with a 7-item Likert-scaled Activity Questionnaire completed by parents (0.87, Alpha coefficient). Subject's severity of disease classifications based on pre-exercise pulmonary functions were as follows: 61% were in the normal category; 26% in mild; 8% in moderate; and 5% in severe. Activity scores ranged from 5 to 33 (x = 22. +/- 6.80). The subjects' levels of fitness were low as determined by their maximal oxygen uptake values. Correlations showed no significant relationships between the activity scores and oxygen uptake measures. Nurses can develop individualized exercise regimens based on clinical and psychosocial data as well as exercise testing for children with cystic fibrosis and their families. PMID- 8509970 TI - Homeless children and their families, Part I: The changing picture. PMID- 8509971 TI - Glucometers: accuracy and precision, Part I. PMID- 8509972 TI - Immunizations: supporting the community's efforts. PMID- 8509973 TI - Heart to heart: teaching pediatric cardiology and cardiac surgery to nurses in St. Petersburg, Russia. PMID- 8509974 TI - A different world, a different view. PMID- 8509975 TI - Listening to parents. PMID- 8509976 TI - Negotiating nurse-patient authority in pediatric home health care. AB - In this qualitative study, pediatric home health nurses described the solitary, ambiguous, and unprogrammed nature of home health nursing. As employees of the family, the nurses in this study found it necessary to negotiate their work tasks and working conditions with family members. In describing the meaning of their work, the nurses emphasized differences between hospital and home health nursing with regard to their authority for care decisions, methods of child discipline, parental control of care, and innovations of nursing routines and interventions. Characteristics of pediatric home nursing are identified in order for these to be communicated to prospective home care nurses, to pediatric nurse educators, and to home health managers. With knowledge of these characteristics, a new home health nurse will be better prepared to negotiate shared patient care responsibilities with the client's family. PMID- 8509977 TI - Nurses' experience caring for anencephalic infants who are potential organ donors. AB - A descriptive study explored the experience, attitudes, and concerns of 75 nurses who gave direct care to anencephalic infants in a program of potential organ donors. One ethical issue for a majority of nurses was concern about whether the program allowed dignity for the life of the infant. Other concerns were whether the infants felt pain, and the infants' physiological responses. PMID- 8509978 TI - Stressors and children's health. AB - This article reviews the literature on the association of stressors and physical and psychological health in childhood. These relationships are considered from a multidisciplinary perspective. Many studies have been published comparing children experiencing a large number of life events with those who experience fewer, with the consistent finding that those with more stressful experiences are significantly more likely to experience illness, hospitalization, or use health services. Although a large body of research exists, a clear picture of the nature and strength of this relationship has not yet emerged. Clarification of the psychophysiological pathways responsible for the associations reported may be important to our understanding of these issues. Such pathways may have their origin in the alteration of immune function. Further research aimed at explication of the complex relationships between the neurological, endocrine, and immune systems and behaviors will need to be multifactorial. Such research has the potential to improve our understanding of psychosomatic phenomena and lead to more effective nursing care. PMID- 8509979 TI - Sibling visitation: how far should the pendulum swing? AB - This study describes development of early interaction between siblings. Subjects (N = 22) were the older siblings (30 to 52 months) of healthy new babies. Data were collected to describe initial contact, regressive behaviors, and extent and quality of sibling interaction at 3 weeks, 5 months, and 7 months. Patterns of visualization, touch, and communication were observed. There was no evidence of sibling regressive behavior. Behaviors were more positive than negative and older siblings were in proximity for initiation of interaction by the new baby at 5 and 7 months. Findings indicate positive sibling relationships may be the norm rather than the exception. PMID- 8509980 TI - Pentoxifylline inhibits HIV-1 LTR-driven gene expression by blocking NF-kappa B action. AB - The drug pentoxifylline (PTX) (1-(5'-oxohexyl) 3,7-dimethylxanthine) down regulates human immunodeficiency virus (HIV-1) long terminal repeat (LTR) directed gene expression in the human monocytic cell line U38. This effect of PTX has been tested in clinical trials. In this investigation, a similar inhibitory effect of PTX on HIV-1 LTR-driven gene expression was observed (a) in a stable transfectant of the human embryo kidney cell line 293-27-2 carrying an expression plasmid construct with the HIV-1 LTR fused to the bacterial lac Z gene, and also (b) by transient transfection of human embryo kidney cells 293 S with fusion plasmid constructs with wild-type [pHIV-LTR-chloramphenicol acetyltransferase (CAT)] or mutated (pHIV-LTR-mut-CAT) nuclear factor kappa B (NF-kappa B) motifs. In both stable and transient transfection studies, 4-beta-phorbol-12-beta myristate-acetate (PMA)-induced or tumor necrosis factor-alpha (TNF-alpha) induced activation of the HIV-1 LTR was correlated with a concomitant elevated level of NF-kappa B interaction with its motifs. The inducibility of HIV-1 LTR driven gene expression by PMA or TNF-alpha in transiently transfected cells was completely eliminated by point mutations in the NF-kappa B motifs, suggesting that NF-kappa B plays a major role in the activation of the HIV-1 LTR by these agents in this cell system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509981 TI - Psychological effects of participation and nonparticipation in a placebo controlled zidovudine clinical trial with asymptomatic human immunodeficiency virus-infected individuals. AB - Psychological effects of participation in Protocol 019, a zidovudine placebo controlled clinical trial, were investigated. Forty-six Protocol 019 subjects and 27 control asymptomatic human immunodeficiency virus-seropositive subjects were assessed at entry, 2 months, 6 months, and after trial modification. At baseline there were no psychological differences. Most Protocol 019 and control subjects were depressed on at least one psychological measure; fewer were anxious. Both groups had improvement over time. By 6 months, Protocol 019 subjects had decreased Beck Depression Inventory (BDI) scores, state anxiety, stress reaction, and symptoms of depression and anxiety. Controls had decreased scores on only the BDI. Over time, the percentage meeting modified DSM III-R criteria for anxiety decreased in both groups and the proportion of Protocol 019 subjects meeting DSM III-R depression criteria decreased. After protocol modification, study subjects were less depressed and distressed than controls. Protocol 019 subjects reduced depression symptoms but controls did not. Clinical trial participation was not deleterious and may have yielded some relative psychological benefit. PMID- 8509983 TI - The effects of intravenous drug use and gender on the cost of hospitalization for patients with AIDS. AB - At present limited data exist describing the hospital use patterns of intravenous drug users (IVDUs) and women with AIDS. Our objective was to determine if frequency of hospitalization, length of stay (LOS), and cost per hospitalization varied by risk status and gender, controlling for a variety of confounders, including severity of illness as measured by the Turner-Kelly-Ball and Justice AIDS severity of illness systems. We performed a population-based cohort study that compared all women (n = 69) and male IVDUs (n = 74) with AIDS diagnosed in Massachusetts in 1987 with a random sample of all male, nonintravenous drug-using patients diagnosed in that year (n = 148). Frequency of hospitalization, LOS, and cost of hospital care were obtained from hospital billing records for 1987 and 1988. Regression analysis showed 42% longer lengths of stay (p < or = 0.001) and 38% higher cost (p < or = 0.001) per hospitalization for IVDUs with AIDS compared with non-IVDU homosexual AIDS patients. No statistically significant differences by gender were observed. Our results suggest that hospital care for IVDUs is likely to be more expensive. Policymakers should incorporate these data when planning for AIDS care. In addition, instruments to assess severity of illness should incorporate information on intravenous drug use. PMID- 8509982 TI - Variability of reporting and lack of adherence to consensus guidelines in human T lymphocyte immunophenotyping reports: results of a case series. AB - Percentages and absolute counts of CD4+ lymphocytes, as determined by T lymphocyte immunophenotyping (TLI), are prognostic, as well as diagnostic, of the course of human immunodeficiency virus type 1 infections and are important indicators for initiating Pneumocystis carinii pneumonia prophylaxis and antiretroviral therapy. In December 1990, we requested that a nonrandom sample of 17 laboratories provide us with typical reports of their TLI results from an immunodeficient patient and from a patient whose TLI results were within the laboratory's normal reference ranges. We also searched published literature and documents proposed by professional organizations for recommendations regarding T lymphocyte testing and reporting. This article compares guidelines for reporting TLI results, as proposed by the National Committee for Clinical Laboratory Standards in Document H42-P, with samples of reports obtained in our case series. Most reports follow some, but not all, of the proposed guidelines. A majority of the laboratories provided interpretations of the results in their reports. We found considerable variation in normal reference ranges. We describe this variation in detail for the CD4+ T-lymphocyte counts and CD4+ T-lymphocyte percentages. This article describes some of the TLI result report forms currently being used and identifies important quality issues in this rapidly expanding area of clinical laboratory testing. PMID- 8509985 TI - No change in incidence and prevalence of HIV among intravenous drug users in Copenhagen from 1985 to 1990. AB - During the years 1984 to 1990, 1,029 intravenous drug users (IVDU), equalling approximately one-third of the estimated total IVDU population in the study area, attended the outpatient venereal disease clinic of Copenhagen for an HIV antibody test. Neglecting samples on HIV-positive persons after the first positive test, 665 IVDU were only tested once, whereas 364 IVDU had 613 tests performed after their first HIV antibody negative result. HIV prevalences calculated for each year showed that the prevalence of 20% in 1985 was significantly higher than those of the following years, varying between 9% and 12% without any statistical differences between these years or evidence of an increase or a decrease. HIV incidence was calculated from the results of the 364 IVDU with an initially negative HIV test, from whom 613 subsequent test results were available and of which 20 showed HIV antibodies. The total risk period was 837 years, and the overall incidence 2.4 per 100 person years without any difference between male and female IVDU, but with a tendency of a decreasing incidence with increasing age. The incidence rates per 100 person years were 2.82 in 1984-1987 and 2.38 in 1988-1990, which is not significantly different. A seroconversion rate of 2.42 (1.51-3.65) per 100 IVDU per year was calculated. With an estimated IVDU population of 3,000 persons in Copenhagen, the yearly number of new HIV infected IVDU can then be estimated to 72 persons (45-110), a figure that is 100% higher than that known from the anonymous national HIV reporting system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509984 TI - The risk of tropical spastic paraparesis differs according to ethnic group among HTLV-I carriers in Inongo, Zaire. AB - Following the finding in 1990 of six HTLV-I-positive cases of tropical spastic paraparesis (TSP/HAM) is a field survey carried out in the city of Inongo (Bandundu, Zaire), the prevalence of HTLV-I infection has been studied by detection of specific antibodies on a randomized sample of the general population. Among the 1,162 subjects surveyed, 36 (3.1%) were found to be HTLV-I seropositive, giving a seroprevalence of 3.2% (CI: 2.1, 4.3) estimated by direct standardization on age and sex distribution given by the census in the city. Among the five major ethnic groups, the Bolia showed the highest prevalence rate (6.5%) but with no detected TSP/HAM cases, while all six TSP/HAM cases were found among the Ntomba, who showed a prevalence rate of only 2.2%. This finding suggests that besides HTLV-I infection, critical environmental and/or genetic cofactors play a part in the development of TSP/HAM. PMID- 8509986 TI - Cutaneous nocardiosis caused by Nocardia nova occurring in an HIV-infected individual: a case report and review of the literature. PMID- 8509987 TI - Presence of human T-cell lymphotropic virus types I and II and coinfection with human immunodeficiency virus in different groups at risk in Argentina. PMID- 8509988 TI - Zidovudine treatment and virus excretion in the cervicovaginal secretions of HIV infected women. PMID- 8509989 TI - [Constituents of Acer nikoense and Myrica rubra. On diarylheptanoids]. AB - The diarylheptanoid constituents of the titled plants and their close plants were reviewed. Many new diarylheptanoids and their glycosides named acerogenin and aceroside were isolated from the stem bark of Acer nikoense, A. griseum and A. triflorum. Myricanone, myricanol and its five new glycosides were isolated from the stem bark of Myrica rubra, and myricanone and galeon, from the stem of M. gale var. tomentosa. The structures of these compounds were determined on the basis of chemical and spectral evidence, and chemotaxonomy of the above plants was briefly discussed. In addition biosynthesis of acerogenin A, revision of the structure for isomyricanone derived from myricanone, and some biological activities of A. nikoense and M. rubra were described. PMID- 8509990 TI - [Our investigation on the chemistry of biologically active natural products. With the object of exploitation for structure determination methods, and elucidation of vital function]. AB - Our investigation on the chemistry of biologically active natural products during the last 40 years since 1953 are reviewed in this paper. The following subjects are discussed: I. photochemical relationship between rhodopsin and compounds related to areca alkaloid, II. furanoid diterpenoid constituents from dioscoreaceae plants and colombo root, III. field desorption and fast atom bombardment mass spectrometry of biologically active natural glycosides and glycosphingolipids, IV. investigation of biologically active marine natural products, 1) constituents of steroid glycoside sulfates from Asteroidea, 2) spine toxins from Acanthaster planci, 3) constituents of triterpenoid glycoside sulfates from Holothuroidea, 4) constituents of isoprenoids from Opisthobranchia and Octocorallia, 5) constituents of glycosphingolipids from Asteroidea. PMID- 8509991 TI - [Synthesis and antibacterial properties of 3-O-alkyl-D-glucose derivatives]. AB - A series of 3-O-alkyl-1,2-O-isopropylidene-alpha-D-glucofuranoses (3-7), 6-deoxy 3-O-dodecyl-6-halo-1,2-O-isopropylidene-alpha-D-glucofuranose s (9-11), and 6 deoxy-3-O-dodecyl-6-halo-D-glucopyranoses (12-14) were prepared from 1,2; 5,6-di O-isopropyridene-alpha-D-glucofuranose and their antibacterial activities were evaluated. The compounds having C12 and C14 alkylchains at C-3 of 1,2-O isopropylidene glucoses were the most effective in vitro antibacterial screening, of which the structure-activity relationships are also discussed. PMID- 8509992 TI - [Purification of pig adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase and influence on microsomal membrane destruction on its enzyme activity]. AB - A 3 beta-hydroxysteroid dehydrogenase/delta 4-delta 5-isomerase (3 beta HSD/isomerase) has been purified to homogeneity from the pig adrenal microsomes by solubilization with sodium cholate, followed by some conventional column chromatographies. The molecular weight of the enzyme was estimated to be 42000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Km value for pregnenolone as the substrate of the purified enzyme was higher than that of the microsomal enzyme. The purified enzyme was less stable for heat treatment than the microsomal binding enzyme. The microsomal enzyme was treated with various agents or enzymes which destroyed the membrane structure. Lipid peroxidation with Fe2+, digestion with phospholipase A2 or C, and the addition of various free fatty acids, imidazole containing compounds and polymyxin B were utilized for the membrane destruction. Consequently, the 3 beta-HSD/isomerase activity was significantly reduced in all cases, and the Km value of the 3 beta-HSD/isomerase for pregnenolone increased. And the Vmax and Vmax/Km values significantly decreased. Therefore, it is strongly suggested that the normal membrane structure plays an important role in the maintenance of the 3 beta-HSD/isomerase activity. PMID- 8509993 TI - [Possibility of lymphatic absorption of epidermal growth factor from intestine]. AB - Epidermal growth factor (EGF) in the milk fat globule membrane (MFGM) emulsion enhanced the absorption of this factor from the intestine, especially to the intestinal lymph. Most of the radioactive EGF administered was degraded to small molecular weight materials. These degraded materials were absorbed and appeared in both the intestinal lymph and portal vein blood. However, a certain portion of EGF, although small, appeared in the lymph maintaining the original molecular mass. The MFGM emulsion used enhanced the lymphatic absorption of intact EGF, suggesting that this dosage form increased the absorption of EGF, protected the degradation of EGF in the intestine or promoted the absorption of intact EGF. The enhancing effect on the absorbed dose percentage of EGF recovered using MFGM emulsion was also observed in the portal vein plasma. However, the effect on the absorption of intact EGF was much larger in the lymph than in the portal vein. PMID- 8509994 TI - [Inducible resistance to macrolide-lincosamide-streptogramin type B antibiotics in Bacillus licheniformis: common structures of macrolide antibiotics capable of inducing the resistance]. AB - Whether or not resistance to macrolide-lincosamide-streptogramin type B antibiotics (MLS) can be induced by many macrolide antibiotics (Mac), was inquired in Bacillus licheniformis EMR. Resistance to MLS in the strain was induced by erythromycin, oleandomycin, clarithromycin, roxithromycin, narbomycin, picromycin, kujimycin A or B, mycinamicin I, or rosamicin. On the contrary, josamycin, spiramycin, tylosin, rokitamycin, midecamycin, and miokamycin as well as lincosamide and streptogramin type B antibiotics could not induce MLS resistance. The results suggest that two common chemical residues of the inducer Mac, that is, 1) a single monosaccharide at C5 in the 14- and 16-membered lactone rings, and 2) one polar group such as dimethylamino or methoxyl at C3' in the sugar, are likely to be responsible for showing the activity of MLS-resistance inducer in Bacillus licheniformis EMR. PMID- 8509995 TI - Modulation of the seizure threshold for excitatory amino acids in mice by antiepileptic drugs and chemoconvulsants. AB - A novel method for the assessment of the threshold for clonic seizures induced by excitatory amino acids based on continuous infusion of the glutamate agonists [alpha-amino-3-hydroxy-5-terbutyl-4-isoxazolepropionate (ATPA), kainate or N methyl-D-aspartate (NMDA)] into the lateral brain ventricle of unrestrained mice is reported. Using this novel method of seizure threshold determination, it was found that systemically administered diphenylhydantoin and carbamazepine elevated the threshold for ATPA and had negligible effects on the threshold for kainate and NMDA. Phenobarbital and trimethadione elevated the threshold for all excitatory amino acids tested, whereas valproate elevated the threshold for ATPA and kainate seizures. Ethosuximide elevated the threshold for ATPA and kainate and decreased the threshold for NMDA seizures. The quisqualate antagonists [2,3 dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline and 1-(4-aminophenyl)-4-methyl 7,8-methylenedioxy-5H-2,3-benzodiazepine] elevated the threshold for ATPA and less so for kainate seizures, whereas the NMDA antagonist 3-((+-)2 carboxypiperazine-4-yl)-propyl-1-phosphonate elevated the threshold for NMDA seizures. 1-(4-Aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine in higher doses was also active against NMDA seizures, whereas 3-((+-)2 carboxypiperazine-4-yl)-propyl-1-phosphonate did so with kainate seizures. Among seven different convulsants, pentylenetetrazol, picrotoxin and the beta-carboline methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate lowered the threshold for seizures induced by excitatory amino acids. Pentylenetetrazol and picrotoxin did so with kainate seizures, whereas methyl 6,7-dimethoxy-4-ethyl-beta-carboline 3-carboxylate lowered ATPA thresholds. Bicuculline, 3-mercaptopropionate, strychnine and pilocarpine were inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8509996 TI - The oral antihypertensive activity of the methylated derivatives of phenyl-2 aminoethyl sulfide. AB - We have reported previously that phenyl-2-aminoethyl sulfide and its derivatives are excellent substrates for dopamine-beta-monooxygenase and produce an antihypertensive effect in spontaneously hypertensive rats after i.p. administration. In the studies reported herein, we demonstrate that alpha-methyl phenyl-2-aminoethyl sulfide and 4-hydroxy-alpha-methyl-phenyl-2-aminoethyl sulfide, the methylated and hydroxymethylated derivatives of phenyl-2-aminoethyl sulfide, respectively, decrease mean arterial pressure in conscious, unrestrained spontaneously hypertensive rats after p.o. administration. This antihypertensive effect after p.o. administration occurs without the undesirable transient rise in blood pressure observed previously after i.p. administration. Results using the methodology of food-reinforced operant conditioned behavior are consistent with the interpretation that the ring hydroxylated derivatives, 4-hydroxy-phenyl-2 aminoethyl sulfide and 4-hydroxy-alpha-methyl-phenyl-2-aminoethyl sulfide, do not penetrate into the central nervous system. This finding supports our contention that the primary site of action for the antihypertensive activity of the sulfides may be the peripheral adrenergic nerve ending. In view of the current high degree of interest in chiral development, the enantiomeric specificity of the antihypertensive activity of alpha-methyl-phenyl-2-aminoethyl sulfide was also evaluated. Results from these studies demonstrate that the (S)-enantiomer of alpha-methyl-phenyl-2-aminoethyl sulfide is more effective in lowering blood pressure after p.o. administration than the (R)-enantiomer. The implications of our findings in terms of the mechanism of action of these compounds are discussed. PMID- 8509997 TI - Characterization of methotrexate elimination and interaction with indomethacin and flurbiprofen in the isolated perfused rat kidney. AB - The mechanism of methotrexate (MTX) renal elimination and the interaction of MTX with the nonsteroidal anti-inflammatory drugs, indomethacin and flurbiprofen, were characterized in the isolated perfused rat kidney. Perfusion studies elucidating MTX renal disposition were performed in perfusate (4.0% bovine serum albumin) at initial MTX concentrations of 1, 5, 12 and 25 micrograms/ml and in controls without MTX. Interaction studies were performed at clinically relevant indomethacin and flurbiprofen concentrations of 2.5 and 10 micrograms/ml, respectively, and a MTX concentration of 25 micrograms/ml (representative of an oncolytic MTX dose). MTX unbound fractions were concentration and interactant independent. Kidney viability was within normal limits for this technique among all perfusions. MTX renal clearance was nonlinear, increasing from 0.310 to 0.434 ml/min over the concentration range studied. Corresponding excretion ratios increased from 0.933 to 1.52, indicative of MTX renal elimination involving the processes of filtration, secretion and reabsorption. Excretion ratio results were supported by tubular transit rate calculations. Interaction studies indicated that there was secretory inhibition of MTX as evidenced by a decrease in both excretion ratio and tubular clearance at 25 micrograms/ml of MTX. Therefore, the secretory component was significantly inhibited by indomethacin and flurbiprofen after concomitant administration of oncolytic doses of MTX. PMID- 8509998 TI - Losartan prevents salt-induced hypertension in reduced renal mass rats. AB - A reduction in functioning renal mass through surgical ablation leads to the development of hypertension and chronic renal failure in rats. Reduced renal mass (RRM) hypertension is more severe and develops more quickly if rats are on high salt intake. It has previously been shown that hypertension in these rats can be prevented by treatment with angiotensin-converting enzyme inhibitors. The current experiment examined the effect of losartan, an angiotensin II antagonist, on blood pressure in RRM and intact rats after a 3-fold increase in salt intake. It was found that chronic treatment with i.v. losartan (3 mg/kg/day) completely prevented sodium-induced hypertension in the RRM rats, whereas neither increased salt intake nor losartan treatment affected blood pressure in the intact rats. The antihypertensive effect of losartan was associated with an apparent renoprotective effect in RRM rats (blood urea nitrogen concentration rose in untreated animals, but remained stable in treated animals), but was not accompanied by chronic changes in water or sodium balance. The ability of losartan to prevent RRM hypertension suggests that angiotensin II is necessary for the development of this model of hypertension. PMID- 8509999 TI - Oxidative stress and thiol modification induced by chronic administration of haloperidol. AB - Haloperidol, a widely used neuroleptic, acts through blockade of dopamine receptors leading to increased turnover of dopamine. Increased turnover of dopamine could lead to excessive production of hydrogen peroxide and, thus, generate oxidative stress. The effect of chronic administration of haloperidol on glutathione (GSH)-protein thiol homeostasis and lipid peroxidation was examined in rat brain regions. The oxidized GSH levels increased significantly, though not substantially, in cortex (CT, 15%), striatum (ST, 28%) and midbrain (MB, 27%). Maximal decreases in GSH levels were noted in CT (23%), ST (28%) and MB (20%) after 1 month of haloperidol administration. The GSH levels recovered thereafter, and after 6 months of haloperidol treatment, the GSH levels were not significantly different from control in ST and MB. The depleted GSH was recovered essentially as protein-GSH mixed disulfide with a concomitant decrease in the protein thiol concentration in all the three regions of the brain. The increase in oxidized GSH concentration represented only 1.8, 2.0 and 3.5% of the depleted GSH in the CT, ST and MB after 1 month of haloperidol administration. The concentration of thiobarbituric acid-reactive products increased significantly up to 3 months of haloperidol treatment, but at the end of 6 months, the levels were substantially decreased. The present study demonstrates that haloperidol administration for 1 month results in significant oxidative stress in CT, ST and MB regions of the brain, as demonstrated by alterations in GSH-protein thiol homeostasis and increased lipid peroxidation products. However, after prolonged administration of haloperidol for 6 months, the GSH-protein thiol homeostasis is restored to a large extent, concomitant with the decrease in the concentration of lipid peroxidation products. Administration of haloperidol leads to development of tolerance (supersensitivity of the dopamine autoreceptors) to neuroleptics, which is associated with decreased turnover of dopamine; this may result in overcoming the oxidative stress generated initially due to increased dopamine turnover. PMID- 8510000 TI - Effect of the chronic dose of diazepam on the intensity and characteristics of the precipitated abstinence syndrome in the dog. AB - The ability of different chronic doses of diazepam to produce dependence was studied in groups of six dogs who received diazepam p.o. (0.05625, 0.225, 0.5625, 4.5, 9 or 36 mg/kg/day) every 8 hr. After 5 to 6 weeks of stabilization, the intensity of precipitated abstinence was measured by benzodiazepine-precipitated abstinence scores (BPAS) after the p.o. administration of graded doses of the benzodiazepine antagonist, flumazenil (0.66, 2, 6, 18, 36 and 72 mg/kg or a placebo). A modified Latin square design was used. Dogs receiving the two lowest stabilization doses of diazepam showed only liminal signs of precipitated abstinence even with 72 mg/kg of flumazenil. The intensity of the precipitated abstinence syndrome increased with the stabilization dose of diazepam. There was also a dose-related increase in BPAS for increasing doses of flumazenil for all doses of diazepam except the 9-mg/kg/day dose. Not only were quantitative differences observed in precipitated abstinence signs for different levels of diazepam dependence, but the pattern of abstinence signs differed also. Dogs dependent on high doses of diazepam were more sensitive to flumazenil than those dependent on lower doses. Furthermore, seizure activity was seen only in dogs dependent on 9 and 36 mg/kg/day of diazepam. BPAS increased linearly with plasma and brain total and free levels of the sum of diazepam and its metabolites (oxazepam and nordiazepam), but not with free plasma and brain levels of diazepam. PMID- 8510001 TI - Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal. AB - The effects of i.v. administered flumazenil (3.0 mg) were studied in healthy male subjects who received pretreatment with p.o. placebo or lorazepam. The duration of placebo or lorazepam (3.0 mg single p.o. daily dose) pretreatment before a flumazenil or placebo injection was 1, 3, 7 or 14 days in four sequential groups of subjects. Initial administration of lorazepam produced a classic sedative profile of effects on various psychomotor/behavioral performance, observer-rated and subject-rated measures. Tolerance to repeated daily administration of lorazepam was suggested by a progressive diminution of performance disrupting effects. In subjects pretreated with placebo, flumazenil increased subject ratings of dizziness over preinjection ratings. Flumazenil produced an immediate reversal of lorazepam effects in subjects who were not tolerant to lorazepam (1- and 3-day pretreatment groups). Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam. Precipitated withdrawal symptoms were evident after 3 and 7 days of lorazepam pretreatment, and there was a tendency toward precipitated withdrawal symptoms (that included one panic attack) after 14 days of lorazepam pretreatment. Precipitated withdrawal was characterized by an elevation in subject-rated symptoms including dizziness, tenseness, tachycardia, perceptual disturbance and sweating. Symptoms were maximal immediately after injection, usually mild in severity and usually resolved within 1 hr. There was no evidence of precipitated withdrawal on psychomotor/behavioral performance or observer ratings. The present study provides the strongest human experimental evidence to date that flumazenil can precipitate withdrawal symptoms after a history of repeated benzodiazepine exposure. PMID- 8510002 TI - Speed of action of various muscle relaxants at the neuromuscular junction binding vs. buffering hypothesis. AB - The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. The onset and recovery time constants of inhibition of brief acetylcholine pulses, caused by long pulses of relaxants for all of the muscle relaxants, were inversely related to apparent dissociation constants (KD values), that ranged from 4.56 microM (gallamine) to 0.11 microM (doxacurium). The kinetics showed only modest temperature dependence (Q10 values of 1/time constant of offset were typically < 1.4). Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510003 TI - Acute effects of calcitonin gene-related peptide on the mechanical and electrical responses of the rat hemidiaphragm. AB - Calcitonin gene-related peptide (CGRP) acutely augments the contractile response of skeletal muscle to both direct and indirect stimulation. However, studies in whole muscle tissues have produced extremely variable results. To determine if differences in stimulation parameters are the source of this variation, the effects of increasing stimulus duration were evaluated in the isolated perfused rat hemidiaphragm. The effect of CGRP on the maximum force of contraction (Fc) was dependent upon the stimulus duration. CGRP (10(-6) M) produced an 11% increase in Fc with a 0.1-msec duration stimulus and a 32% increase with a 1.0 msec stimulus. In contrast, CGRP decreased the time for twitch relaxation and this effect was independent of stimulus duration. Additional studies demonstrated that CGRP shortened the relative refractory period. Compound muscle action potential recordings revealed that stimulus durations greater than 0.5 msec produced a second peak of electrical activity with an associated increased Fc. The effects of CGRP on Fc corresponded to the effects of CGRP on this second peak of compound muscle action potential activity. We conclude that, by decreasing the relative refractory period of the muscle tissue, CGRP enhances the potential for repetitive stimulation with commonly used experimental parameters. PMID- 8510004 TI - Progesterone and mifepristone modify principally the responses of circular myometrium to oxytocin in preparturient rats: comparison with responses to acetylcholine and to calcium. AB - We have recently reported that in the pregnant rat myometrium the synthetic OT/AVP V1 antagonist d(CH2)5[Tyr(Me)2]OVT has similar pA2 values against oxytocin (OT) or arginine vasopressin in longitudinal myometrial strips and against arginine vasopressin in circular myometrial strips. However, the antagonist is inactive against OT in circular strips, suggesting that the receptor involved in the action of OT in circular muscle is distinct from the OT receptor in longitudinal muscle. In this study, models of progesterone-blocked and progesterone + mifepristone-induced rat parturition were designed to check whether progesterone modulated OT responsiveness differentially in the two myometrial layers. Responses to OT were measured in organ bath experiments and compared with responses to acetylcholine and to calcium ions (Ca2+) in depolarized myometrial strips. Compared with control animals at day 21 of pregnancy, maximal responses to OT in longitudinally cut strips from progesterone or progesterone + mifepristone-treated rats were only marginally affected by steroid treatments. In contrast, progesterone almost totally abolished responses to OT in the circular myometrium, whereas mifepristone treatment restored responses to those seen at spontaneous parturition. In both muscle layers, responses to acetylcholine were unaffected by steroid treatments and those to Ca2+ were decreased by progesterone treatment (however, to a lesser extent than those of OT) and were restored by mifepristone. These results suggest the presence of two populations of OT receptors in the myometrium: a constitutive type of receptor predominent in longitudinal muscle and a progesterone-regulated receptor present in circular muscle. PMID- 8510005 TI - Dobutamine pharmacokinetics and pharmacodynamics in normal children and adolescents. AB - Pharmacokinetic and pharmacodynamic data on adrenergic agents in children have revealed wide ranges of plasma clearance rates and hemodynamic responses in patients with critical illnesses or myocardial dysfunction. In order to more clearly elucidate the underlying pharmacologic processes, graded i.v. dobutamine infusions of 0.5, 2.5 and 5.0 micrograms/kg/min were sequentially administered to healthy children and adolescents. Plasma dobutamine concentrations and hemodynamic responses, including echocardiographic measures of systolic and diastolic function, were determined at each infusion rate. Pharmacodynamic data were evaluated by both threshold modeling and mean hemodynamic responses to each infusion rate. Mean plasma dobutamine clearance was 115 +/- 63 ml/kg/min, with an intersubject variability greater than 5-fold. These data establish that the previously published wide variability in dobutamine clearance is not due simply to underlying disease states. Dobutamine clearance was linear over the dosage range evaluated. Dobutamine improved systolic function even at plasma concentrations attained with infusion rates as low as 1 to 2 micrograms/kg/min. The improved systolic function was at least partially due to inotropic effects. In addition, dobutamine improved diastolic function and reduced afterload. Chronotropic effects were observed in only two subjects and only at higher plasma concentrations than the other hemodynamic effects. Individualized threshold modeling effectively described the log-linear relationship between plasma dobutamine concentration and hemodynamic response beyond the threshold concentration. PMID- 8510006 TI - Dose- and time-dependent changes in phencyclidine metabolite covalent binding in rats and the possible role of CYP2D1. AB - We determined whether chronic dosing with phencyclidine (PCP) could affect the in vitro function of liver microsomal enzymes in male Sprague-Dawley rats. PCP chronic dosing of rats (n = 3 per group) for 3 days with 2.5, 10 and 18 mg/kg/day caused a dose-dependent decrease (23, 36 and 53%, respectively) in the ability of the microsomal enzymes to bind covalently PCP metabolites. The 10- and 18 mg/kg/day dosing groups were significantly different from the 3-day saline infused control group (P < .05). The results from time-dependent dosing studies indicated PCP covalent binding was significantly reduced (P < .05) in rats (n = 3 per group) infused with 18 mg/kg/day of PCP for 1, 2, 3, 4 and 10 days. Subsequently, it returned to near control values in rats infused for 20 days. In parallel with the time-dependent decreases in covalent binding, the concentrations of at least three phase I PCP mono- and dihydroxylated metabolites were also significantly reduced (P < .05) at the earlier time periods of dosing (3 and 10 days), but the rate of their formation returned to near normal values by 20 days of dosing. Total cytochrome P450 content did not differ from the control groups at any of the doses or time points. As dose- and time-dependent decreases in covalent binding suggested a specific metabolic pathway or isoenzyme was affected, we studied the affect on specific isoenzyme pathways. For these studies a series of cytochrome P450 inhibitors were used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510007 TI - Indomethacin- and desamino-8-D-arginine vasopressin-induced lithium reabsorption is not amiloride sensitive in humans. AB - This study was undertaken to analyze whether the mechanism of decreased fractional lithium excretion (FELi) induced in humans by the prostaglandin synthesis inhibitor indomethacin and the vasopressin analog desamino-8-D-arginine vasopressin (d-DAVP) is amiloride inhibitable. Eight sodium-restricted (10 mmol/day) healthy volunteers underwent clearance studies to evaluate the effects of indomethacin (50 mg tid for 6 days), amiloride (10 mg twice before the clearance study) and d-DAVP (4 micrograms, i.v.), and combinations of these drugs. Despite the sodium restriction, amiloride had no effect on FELi, although the dosage was sufficient to cause a 6-fold increase in sodium excretion, and potassium retention. Compared to a base-line value of 27.9 +/- 2.1%, FELi fell to 20.7 +/- 2.1% after indomethacin (P < .01) and to 22.4 +/- 1.5% after d-DAVP (P < .01). When d-DAVP was administered during indomethacin, the FELi fell to 18.0 +/- 1.4%. Compared to indomethacin alone, this represented no significant further change. Amiloride did not prevent the fall in FELi caused by indomethacin or d DAVP or both. These data indicate that in humans, 1) sodium restriction does not cause amiloride-sensitive lithium reabsorption, and 2) the lithium reabsorption caused by d-DAVP and indomethacin is not amiloride sensitive. PMID- 8510008 TI - Species differences in the pharmacology of the 5-hydroxytryptamine2 receptor: structurally specific differentiation by ergolines and tryptamines. AB - Species differences in the recognition of a series of ergolines by the 5 hydroxytryptamine2 (5-HT2, serotonin2) receptor were investigated in four species, the rat, pig, squirrel monkey and human. In pig frontal cortical membranes the initial studies showed that the ergolines gave shallow displacement curves against [3H]ketanserin binding. The component of [3H]ketanserin binding having low affinity for the ergolines was determined to be the result of [3H]ketanserin binding to alpha-1 adrenergic receptors. Thus, in all subsequent assays prazosin was used to mask [3H]ketanserin binding to alpha-1 adrenergic receptors. Examination of a series of ergolines revealed a distinct pattern in the species selectivity. Compounds that were unsubstituted at the N1 position of the ergoline nucleus showed higher affinity for the pig, squirrel monkey and human 5-HT2 receptors than for the rat. Conversely, compounds that had an N1 isopropyl substituent showed higher affinity for the rat receptor compared to the pig, squirrel monkey and human 5-HT2 receptors. For example, LY53857, a widely used 5-HT2 antagonist, has an isopropyl substituent at position N1 of the ergoline nucleus and exhibited a 4- to 5-fold higher affinity for the rat 5-HT2 receptor, whereas its N1-unsubstituted homologue, LY86057, had more than 10-fold higher affinity for the pig, squirrel monkey and human 5-HT2 receptors. Similar results were seen with three additional ergoline pairs, each having different substituents at the C8 position compared to LY53857. Even an N1-substitution on LY53857 as small as a methyl group, LY108742, resulted in the compound having higher affinity for the rat 5-HT2 receptor compared to the other species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510009 TI - Modulation of cardiac performance by amiloride and several selected derivatives of amiloride. AB - Amiloride and its derivatives (benzamil, dichlorobenzamil, 5-(N,N-dimethyl) amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, (N,N-hexamethylene)- amiloride and 5-(N-methyl-N-isobutyl)-amiloride) are commonly used as selective blockers of Na+/Ca++ exchange or Na+/H+ exchange. Very little information is currently available regarding their effects on cardiac performance. It was observed that addition of amiloride or any of the selected derivatives to the coronary perfusate of the right ventricular wall produced a potent depressive effect on peak developed tension and the rates of tension generation and dissipation. The concentrations at which this occurred are those that are commonly used in ischemia or hypoxia studies. Significantly, the depressive action of the drugs increased with the perfusion duration and never achieved a stable level. An initial, transient positive inotropic effect was observed with some of the drugs. If the drug concentration and perfusion time was limited, the effects were reversible. All of the drugs except amiloride produced extra systoles. The drugs were capable of blocking Ca++ transients in isolated cardiomyocytes but had little effect on intracellular pH. The drugs lengthened the action potential duration and decreased the action potential amplitude and upstroke velocity. Their effects on cardiac performance may involve a complex inhibition of Ca++ influx and K+ efflux in addition to a stimulation of a nonselective cation current. It is concluded that amiloride and its analogs have striking effects on cardiac performance which may be unrelated to their capacity to inhibit Na+/Ca++ or Na+/H+ exchange. In summary, the use of these drugs is not normally recommended in cell or tissue perfusion experiments because of their nonselectivity. However, if the drug concentration and perfusion time is controlled carefully, interpretable data may be obtained in some cases. PMID- 8510010 TI - Kinetic analysis of hepatobiliary transport of organic anions in Eisai hyperbilirubinemic mutant rats. AB - The hepatobiliary transport of nonmetabolizable organic anions [cefodizime, dibromosulfophthalein, and indocyanine green (ICG)] was kinetically analyzed in Eisai hyperbilirubinemic rats (EHBR; Sprague-Dawley-derived mutant rats with conjugated hyperbilirubinemia). In EHBR, the biliary excretion of these anions was remarkably impaired, whereas the alteration in initial plasma disappearance was minimal. The kinetic analysis of the disposition of these ligands revealed 1) that the transport rate via bile canalicular membrane was severely impaired in EHBR for cefodizime and dibromosulfophthalein and 2) that the intracellular transport rate of ICG was decreased in EHBR, which contributed more than the decrease in the canalicular membrane transport to the net reduction of the excretion rate of ICG in EHBR. The latter finding was also supported by the in vitro results; the binding of ICG to ligandin(s) in EHBR was less extensive compared with that in normal rats, resulting in the higher distribution of ICG to organelle. Because the ligand molecules bound to organelle diffuse within the cells much more slowly than the molecules in the cytosol, the higher distribution of ICG to organelle in EHBR results in the reduction in the intracellular transport rate. These results indicate that the differential impairment mechanisms can be proposed for the excretion of organic anions: One is the impairment in the transport rate across the canalicular membrane, the other is the impairment in the intracellular transport rate. PMID- 8510011 TI - Inhibition of gastric acid secretion in vivo and in vitro by an inhibitor of Cl( )-HCO3- exchanger, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. AB - The mode of action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl(-)-HCO3- exchanger, on gastric acid secretion has been studied in vitro and in vivo. In the mouse isolated whole stomach preparation, DIDS (100 microM-1 mM) inhibited gastric acid secretion induced by histamine or bethanechol in a concentration-dependent fashion. On the other hand, DIDS, at a concentration enough to reduce the stimulated acid secretion, did not inhibit basal acid secretion in the resting preparation. In the perfused stomach of urethane-anesthetized rats, DIDS (1-10 mg/kg i.v.) inhibited gastric acid secretion stimulated by histamine, bethanechol or tetragastrin, whereas DIDS did not inhibit basal acid secretion. In pylorus-ligated rats, DIDS (3-30 mg/kg) administered intraduodenally also inhibited gastric acid output as well as gastric juice volume when administered immediately after ligation. When injected 6 h before ligation, DIDS inhibited the gastric acid secretion. However, this potency was weak in comparison with that observed when DIDS was administered immediately after ligation. These results demonstrate that DIDS can inhibit stimulated gastric acid secretion in vitro and in vivo, probably through its inhibitory effect on the Cl(-)-HCO3- exchanger. PMID- 8510012 TI - Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways. AB - The effect of genetic obesity and phenobarbital treatment on hepatic conjugation pathways was evaluated in the obese Zucker rat. Acetaminophen pharmacokinetic parameters were examined in vivo after a 30-mg/kg acetaminophen intravenous bolus dose in the presence and absence of phenobarbital treatment. Glucuronidation and glutathione conjugation pathways were studied in vitro in obese and lean Zucker rats after phenobarbital treatment. Obese Zucker rats demonstrated a higher glucuronidation capacity as evidenced by a higher formation clearance of acetaminophen glucuronide and greater UDP-glucuronosyltransferase (UDPGT) activity toward acetaminophen and p-nitrophenol compared with lean controls. Sulfate and glutathione conjugation pathways were not affected by genetic obesity. Obese Zucker rats possessed a higher total hepatic glutathione content due to greater liver weight. Phenobarbital treatment enhanced glucuronidation of acetaminophen and structurally related compounds (i.e., p-nitrophenol) similarly in both phenotypes, but the treatment failed to induce morphine UDPGT in the obese Zucker rat. No effect of phenobarbital was observed on sulfate conjugation, gamma-glutamyl cysteine synthetase activity or hepatic glutathione content in obese or lean Zucker rats. Similar increases in glutathione transferase activities were observed in animals of both phenotypes after phenobarbital treatment. This study demonstrates that glucuronidation is enhanced in genetically obese rats, whereas phenobarbital causes normal induction of several enzymes of the glucuronidation and glutathione conjugation pathways in the obese Zucker rat. However, morphine UDPGT was not induced by phenobarbital, suggesting that obese Zucker rats may possess a defect in the induction of this enzyme similar to that already described for the CYP2B gene in this strain. PMID- 8510013 TI - The gastrin/cholecystokinin-B receptor antagonist L-365,260 reduces basal acid secretion and prevents gastrointestinal damage induced by aspirin, ethanol and cysteamine in the rat. AB - L-365,260, a nonpeptide antagonist of gastrin/CCK-B receptors, was evaluated in receptor binding, antisecretory and gastrointestinal damage assays. L-365,260 binds potently and stereo-selectively to gastrin and CCK-B sites in guinea pig tissue. In contrast, L-365,260 binds to the isolated canine parietal cell gastrin receptor weakly, and without stereoselectivity. In the pylorus-ligated rat, low doses of L-365,260, given i.v., attenuated pentagastrin-stimulated acid secretion, whereas higher doses were required to inhibit both histamine stimulated and basal acid secretion. In an aspirin-induced gastric damage model, L-365,260 was 2.4-fold less potent than the standard histamine H2 antagonist cimetidine in preventing gastric damage when given i.v., and was 8.3-fold less potent than cimetidine when given p.o. Moreover, the ED50 value for L-365,260, given i.v., in prevention of aspirin-induced gastric damage (11.5 mg/kg) agreed well with its ED50 value for inhibition of basal acid secretion (12.6 mg/kg). At doses as great as 100 mg/kg p.o., neither L-365,260 nor cimetidine had an effect on ethanol-induced gastric damage. L-365,260, although p.o. less bioavailable relative to cimetidine in the aspirin gastric damage model, was as potent as cimetidine in the prevention of cysteamine-induced duodenal ulcers in the rat. We conclude that the gastrin/CCK-B receptor antagonist L-365,260, at doses supramaximal for the inhibition of pentagastrin-stimulated secretory responses in vivo, inhibits gastrointestinal damage in models of peptic ulcer disease by an antisecretory mechanism of action. PMID- 8510014 TI - Extracellular acidosis ameliorates metabolic-inhibitor-induced and potentiates oxidant-induced cell death in renal proximal tubules. AB - The effect of extracellular acidosis on different types of cell injury and death was examined using suspensions of rabbit renal proximal tubules. Cell death produced by the mitochondrial inhibitors rotenone, antimycin A, carbonyl cyanide p-trifluoromethoxyphenylhydrazone and oligomycin and by the ion exchangers valinomycin, nigericin and monensin was ameliorated by reducing extracellular pH (pHe) from 7.4 to 6.4. The protection lasted for more than 5 hr and was not due to the release of mitochondrial inhibition or to the maintenance of tubular ATP levels. In contrast, extracellular acidosis potentiated the cell injury and death produced by the oxidants t-butyl hydroperoxide, H2O2 and ochratoxin A. Because a decrease in pHe resulted in an increase in lipid peroxidation and in glutathione disulfide formation, and caused a decrease in glutathione peroxidase and glutathione reductase activities, the mechanism of this potentiation is most likely the result of an increase in free-radical production or a decrease in free radical detoxification. The findings with the oxidants are in marked contrast to those in hepatocytes. These results show that renal cell death as a consequence of mitochondrial inhibition is sensitive to the protective effects of extracellular acidosis and that the effects of extracellular acidosis on cell death are dependent on the mechanism of injury. PMID- 8510015 TI - Pulmonary thromboembolism-induced alterations in nitric oxide release from rat circulating neutrophils. AB - We have earlier reported that neutrophils play an important role in pulmonary thromboembolism. The effect of circulating polymorphonuclear leukocytes (PMNL) isolated from normal and thrombotic rats was, therefore, studied on platelet aggregation in platelet-rich plasma. PMNL inhibited the platelet aggregation in a concentration- and time-dependent manner at 37 degrees C. The platelet aggregation inhibitory response of PMNL was more pronounced in the presence of superoxide dismutase and was abolished by hemoglobin and methylene blue. These observations suggested that the inhibitory effect of PMNL on platelets was mediated by neutrophil-derived relaxing factor. PMNL, obtained after thromboembolism, inhibited the platelet aggregation response more strongly due to an increased release of nitric oxide from them. It is suggested that PMNL play an important role in the regulation of hemostasis. PMID- 8510016 TI - 8-(Diethylamino)-octyl-3,4,5-trimethoxybenzoate inhibits cromakalim-induced 86Rb efflux from the rat aorta. AB - The effects of 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) on cromakalim-induced 86Rb efflux and vasorelaxation in the rat aorta have been assessed. TMB-8 inhibited cromakalim (10 microM)-induced 86Rb efflux with an IC50 of 0.50 +/- 0.15 microM (n = 4; IC50 for glyburide 0.17 +/- 0.05 microM, n = 4), but it produced minimal antagonism of the cromakalim-induced vasorelaxation (rings precontracted with 30 mM KCl-PSS) at TMB-8 concentrations < or = 3 microM. TMB-8 at 10 microM produced significant inhibition of the cromakalim-induced vasodilation. Inhibition of cromakalim-induced 86Rb efflux produced by TMB-8 was little affected by raising the KCl concentration to 30 mM (inhibition by 0.5 microM TMB-8: 62.9 +/- 6.9 and 52.5 +/- 10.9% in 4.6 and 30 mM KCl, respectively; n = 4 for both). Similarly, the inhibitory effects of glyburide on the cromakalim induced 86Rb efflux were minimally affected by this maneuver. TMB-8 was approximately equipotent against the increase in 86Rb efflux generated by either 1 or 10 microM cromakalim (IC50: 0.73 +/- 0.11 and 0.65 +/- 0.33 microM, respectively; n = 4 of both). In contrast, the glyburide IC50 was reduced approximately 10-fold by reducing the concentration of cromakalim used from 10 to 1 microM (IC50: 182.5 +/- 4.8 and 19.5 +/- 2.6 nM, respectively; n = 4 for both). We hypothesize that TMB-8 inhibits the potassium channel that is opened by cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510017 TI - Stereoselectivity in glutathione conjugation and amidase-catalyzed hydrolysis of the 2-bromoisovalerylurea enantiomers in the single-pass perfused rat liver. AB - Stereoselective glutathione conjugation and amidase-catalyzed hydrolysis of [(R)- and (S)-]2-bromoisovalerylurea (BIU), yielding bromoisovaleric acid (BI) and urea, have been observed in the rat in vivo and in isolated rat hepatocytes. The metabolism of enantiomeric (R)- and (S)-BIU was presently examined in the single pass perfused rat liver with varying input concentrations (8-250 microM). Steady state hepatic extraction ratios for (R)-BIU (0.6) were constant and higher than those for (S)-BIU, whose extraction ratio decreased from 0.36 (8 microM) to 0.23 (236 microM). (R)- and (S)-BIU were excreted unchanged only minimally into bile. [14C-Urea](R)-BIU underwent amidase-catalyzed hydrolysis to yield [14C]urea (15 24% of rate in) and conjugation to form the (S)-glutathionyl conjugate (31-35% of rate in); two metabolites, most likely the cysteinyl and dipeptide conjugates of BIU (10% of rate in), were found. [3H-Isovaleryl](S)-BIU formed much less amidase hydrolyzed product, [3H]BI (1-2% of rate in) less (R)-glutathionyl conjugate (9 18% of rate in), but appreciable amounts (14-17% of rate in) of three other metabolites, of which two were most likely the cysteinyl and glycinylcysteinyl conjugates of BIU. When the glutathione conjugation products (glutathione, cysteine and cysteinylglycine conjugates) were summed, the total glutathione conjugation rate for (R)-BIU (44% of rate in) exceeded that for (S)-BIU (34 to 24% of rate in). Fitting of data to the Michaelis-Menten equation revealed similar Km for glutathione conjugation, but a 2-fold higher Vmax for (R) BIU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510018 TI - Endothelin differentially affects rat gastric longitudinal and circular smooth muscle. AB - We have determined the response of two types of rat gastric smooth muscle to the cumulative addition of endothelin-1 (ET-1). Both the longitudinal smooth muscle (tonic) from the forestomach and the circular smooth muscle (phasic) from the fundus were used in this study. Longitudinal smooth muscle contracted in a concentration-dependent manner in response to ET-1. The ET-1-induced contractions were abolished by the use of either nifedipine or calcium-free solutions. The maximal stress developed was 1.13 +/- 0.12 x 10(5) N/m2, or about 61% of the maximal carbachol response in this tissue. The EC50 for the ET-1-induced contraction was 11.4 +/- 2.3 nM. In contrast to the contractile effect on longitudinal smooth muscle, ET-1 produced a potent concentration-dependent inhibition of both the spontaneous phasic activity and carbachol-stimulated activity of the circular smooth muscle. The maximal inhibitory effect in response to ET-1 occurred at about 10 nM. The abolition of phasic activity lasted about 15 minutes before phasic activity returned. ET-1 also inhibited carbachol-induced increases in the phasic activity of circular smooth muscle with a similar potency. Inhibitors of arachidonic acid products, indomethacin or nordihydroguaiaretic acid, did not affect the response to ET-1 of either longitudinal or circular smooth muscle. Similarly, inhibition of nitric oxide, vasoactive intestinal peptide (VIP) calcitonin-related peptide (CGRP) and inhibition of endogenous neural pathways by tetrodotoxin (TTX), atropine, hexamethonium, cold storage or phentolamine did not reverse the inhibitory response of the circular smooth muscle to ET-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510019 TI - Kinetics of sequential metabolism. I. Formation and metabolism of oxazepam from nordiazepam and temazepam in the perfused murine liver. AB - In murine liver, temazepam (TZ) and nordiazepam (NZ) are mainly metabolized via N demethylation and C3-hydroxylation, respectively, to form a common metabolite, oxazepam (OZ), which is then glucuronidated. With these precursors, we tested the hypotheses that the sequential metabolism of a primary metabolite (OZ) is less than that of the preformed metabolite and is dependent on the effective intrinsic clearance (unbound fraction x intrinsic clearance) of its precursor, as predicted by the parallel tube and dispersion models of hepatic drug clearances. Mouse livers were perfused with tracer concentrations of [14C]-NZ, [14C]-TZ and [3H]NZ in a single-pass fashion (2.5 ml/min). The steady-state extraction ratio (E) of [3H]NZ, [14C]NZ and [14C]TZ were 0.29, 0.40 and 0.49, respectively (P < .01), whereas the fractional metabolism (formation rate/total elimination rate of drug) of [3H]-NZ, [14C]NZ and [14C]TZ to form OZ was 0.39, 0.79 and 0.68, respectively. Values of E of [3H]NZ and [14C]NZ and fractional metabolism for OZ formation had differed because of a kinetic isotope effect (around 3.5) that affected the C3 hydroxylation of [3H]NZ. The extraction ratios of OZ (E[OZ,P]) arising from [14C] NZ and [14C]TZ were both 0.056, and were less than that for preformed OZ (E[OZ]), previously found to be 0.125. The parameter E[OZ,P] was poorly correlated with the extraction ratio of the precursor, was overestimated by the parallel tube and dispersion models, but was highly correlated with the effective intrinsic clearance of the precursor (unbound fraction x intrinsic clearance).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510020 TI - Kinetics of sequential metabolism. II. Formation and metabolism of nordiazepam and oxazepam from diazepam in the perfused murine liver. AB - Pharmacokinetic theory dictates that the extent of ensuing metabolism of a formed metabolite during drug transit through the liver is influenced by the number of consecutive reactions required for its genesis and the total intrinsic clearances of the precursors. This hypothesis was tested in the perfused murine liver by examining the successive conversion of the precursor diazepam (DZ) to its primary metabolite nordiazepam (NZ), and then the secondary metabolite oxazepam (OZ) and, finally, the tertiary metabolite, the oxazepam glucuronides. The concomitant C3 hydroxylation of DZ to temazepam, which can also be N-demethylated to form OZ, was minimal. The hepatic extraction ratios of NZ (E[NZ,DZ]) and OZ (E[OX,DZ]) after administration of [14C]DZ were compared to those obtained previously from [14C]NZ (E[NZ] and E[OZ,NZ]) and [3H]OZ (E[OZ]). The ability of three hepatic clearance models, the well-stirred, parallel-tube and dispersion models, to predict the experimental E[NZ,DZ] and E[OZ,DZ] was evaluated. DZ was highly extracted by the murine liver (E[DZ] = 0.95). The metabolism of NZ, generated in situ from DZ, was greater than that of preformed NZ (E[NZ,DZ] = 0.51; E[NZ] = 0.4), whereas E[OZ,DZ] (0.066) was similar to E[OZ,DZ] (0.056) and less than E[OZ] (0.0125). The unexpected observation of E[NZ,DZ] > E[NZ] may be explained by the coupling of N-demethylation and C3-hydroxylation/glucuronidation reactions or by a sequestration of hydrophobic substrates within the enzymic space, favoring sequential metabolism of products formed in situ. The atypical kinetic behavior of generated NZ may have also influenced the ensuing metabolic fate of its product, OZ, such that E[OZ,NZ] approximately E[OZ,DZ].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510021 TI - Characterization of 4-aminopyridine block of the transient outward K+ current in adult rat ventricular myocytes. AB - The blocking action of 4-aminopyridine (4-AP) on the transient outward K+ current (ITO) in isolated rat ventricular myocytes was studied using the whole-cell configuration of the patch-clamp technique. 4-AP inhibition of ITO was concentration-dependent with half-maximal block occurring at 0.2 mM. At high concentrations (> 1 mM), 4-AP appeared to slow both the activation and inactivation phases of ITO. This resulted in a crossover phenomenon where in the presence of 4-AP the outward current was less than control at the beginning of a depolarizing pulse but crossed over during the pulse to become greater than control. Inhibition of ITO by 4-AP was voltage-dependent. Steady-state block of ITO by 4-AP was greatest at or near resting membrane potentials (i.e., -70 mV) but decreased with membrane depolarization. The voltage-dependence of block was steep and was well described by a Boltzmann relationship with a slope factor of approximately 4 mV. The midpoint potential for block was dependent on the concentration of 4-AP, being -41.6 +/- 0.4 mV (n = 9), -40.7 +/- 1.3 mV (n = 6), 34.0 +/- 1.6 mV (n = 5) and -30.1 +/- 0.2 (n = 15) at 0.3, 1, 3 and 10 mM, respectively. The midpoint potential for activation was -12.6 mV and was -46.9 mV for inactivation. The concentration-dependence of the voltage-dependence of 4-AP block can be explained by assuming that the sequential closed states through which the channel passes during activation exhibit successively lower affinities for 4-AP. Onset of ITO block by 4-AP was slow. The association (kON) and dissociation. (kOFF) rate constants for binding at -70 mV were: kON = 207 M-1 s-1 and kOFF = 0.090 s-1. The time constant for unblock (tau UNBLOCK) of ITO at 0 mV was independent of 4-AP concentration indicating that there was no binding of 4 AP at this potential. kOFF (1/tau UNBLOCK) at 0 mV was 2.4 s-1 which is approximately 25-fold faster then at -70 mV. The results suggest that 4-AP binds most strongly to closed channels with the inactivation gate open. The conformational changes that occur during channel opening induce a decrease in affinity for 4-AP so that when the channel is in the open state, 4-AP binding is at its weakest. The processes of 4-AP block and inactivation appear to be mutually exclusive. PMID- 8510022 TI - Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. AB - Nicotinic acetylcholine receptors present on cultured hippocampal neurons from fetal rats were characterized by means of whole-cell patch-clamp technique, using a number of structurally divergent agonists and highly selective antagonists. Based upon the decay kinetics of the currents elicited by 3 mM acetylcholine (ACh) and their sensitivities to agonists and antagonists, the neurons were shown to exhibit four current types, IA, IB, II and III. Rapidly decaying currents (type IA) that were blocked by alpha-bungarotoxin (10 nM), kappa-bungarotoxin (10 nM) and methyllycaconitine (MLA, 1 nM) were the most frequent and were found in 83% of the neurons tested. Type II currents (found in 5% of the neurons) were blocked by dihydro-beta-erythroidine (10 nM), and by high concentrations of MLA and kappa-bungarotoxin (100 nM each) but not by alpha-bungarotoxin (100 nM). Type III currents (elicited in 2% of the neurons) decayed slowly and were blocked by (+/-)-mecamylamine (1 microM) but not by alpha-bungarotoxin, kappa-bungarotoxin or MLA (each at 100 nM). Some of the cells (10% of the neurons) had mixed responses (named type IB), which were only partially blocked by MLA (1 nM) or dihydro-beta-erythroidine (10 nM) alone and were completely blocked by combination of the two agents. The order of potency of agonists in activating the currents was the following: for type IA, (+)-anatoxin-a >> 1,1-dimethyl-4-phenyl piperazinium > (-)-nicotine > cystisine > ACh > carbachol > (+)-nicotine > arecoline > suberyldicholine; for type II, ACh > (+)-anatoxin-a > (-)-nicotine > 1,1-dimethyl-4-phenyl-piperazinium > carbachol > cytisine > (+)-nicotine > suberyldicholine > arecoline. Certain agonists were particularly useful in discriminating among the various types of currents: ACh, carbachol, (-)-nicotine and suberyldicholine for type II, and cytisine for type III currents. The EC50 of ACh was approximately 130 microM for type IA and approximately 2 microM for type II currents. A marked inward rectification was observed with type II, whereas type IA currents showed very little inward rectification. Differences observed in the pharmacological and functional properties of the nicotinic currents imply the expression of at least three structurally distinct nicotinic acetylcholine receptor subtypes in hippocampal neurons. The possible involvement of these currents in the transduction of signals is discussed. PMID- 8510024 TI - Administration of 3,3'-iminodipropionitrile to the rat results in region dependent damage to the central nervous system at levels above the brain stem. AB - Axonal swellings and neurofilamentous accumulations in the brain stem, spinal cord and peripheral nervous system are the most widely documented effects of exposure to 3,3'-iminodipropionitrile (IDPN). Evidence from morphological and functional studies, however, suggests that IDPN also may damage areas of the central nervous system above the level of the brain stem. To examine this possibility, we evaluated the astrocyte reaction to injury as an indirect means of detecting potential sites of IDPN-induced damage to the central nervous system. An immunoassay for the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), was used to quantify gliosis. Rats were given IDPN (0-600 mg/kg/day i.p.) for 3 days. The concentration of GFAP in discrete brain regions was examined at postdosing times ranging from 3 days to 3 weeks. IDPN caused time-, dose- and region-dependent increases in GFAP; elevations were observed in the pons-medulla, midbrain, cerebral cortex and olfactory bulbs, but not in cerebellum, hypothalamus, hippocampus and striatum. Of these areas, cortex and olfactory bulbs showed the largest increases. Dissection of cortex into four subregions showed that the IDPN-induced increase in cortical GFAP was relatively uniform across this brain region. Application of the de Olmos cupric-silver degeneration stain to IDPN-treated tissue revealed intense argyrophilia in the glomerular layer of the olfactory bulbs and diffuse staining of axons in several regions of the cortex. The data indicate that IDPN is neurotoxic to the olfactory bulbs and cortex of the rat. PMID- 8510025 TI - Quantitative analysis of concentration-response curves for precipitated abstinence responses in the opiate-dependent guinea pig ileum. AB - Our group has introduced a theoretical model of drug-receptor-effector interactions that can account for most of the kinetic aspects of opiate dependence and abstinence. The present study analyzes the experimental concentration-response curves for precipitated abstinence responses in the isolated guinea pig ileum and compares them with the curves generated by the mathematical model. Two experimental series were included: in the first, the effects of morphine exposure time on dependence development were analyzed; in the second, the effects of morphine concentration were studied. The results show that both the exposure time and morphine concentration determine the magnitude of precipitated abstinence responses. Dependence can be detected after exposure times to opiates as short as 7.5 min. The concentration-response curves for abstinence responses precipitated by naloxone in ilea exposed to morphine for different periods showed: 1) an initial increase in Emax; 2) a parallel shift to the left in the position of the abstinence curves as dependence develops; and 3) an asymptotic limit to the displacement on the left. The results presented here fit well with theoretical predictions. Practical and theoretical implications are discussed. PMID- 8510023 TI - Identification and functional characterization of a new agonist site on nicotinic acetylcholine receptors of cultured hippocampal neurons. AB - Electrophysiological and biochemical techniques were used to demonstrate that alpha-bungarotoxin-, methyllycaconitine-sensitive neuronal nicotinic acetylcholine receptors (nAChRs) can be activated via a novel agonist site(s). The residue proposed to be essential to this site is the amino acid Lys-125 of the receptor alpha subunit. In outside-out patches excised from cultured hippocampal neurons, physostigmine (PHY) and 1-methyl-PHY activated single channels whose main conductances were 46 and 23 pS. This action was insensitive to DL-2-amino-5-phosphonovaleric acid, atropine, tetrodotoxin and competitive nicotinic antagonists, but blocked by benzoquinonium or FK1, a nAChR-specific antibody raised against rat muscle nAChR alpha subunits that binds to the novel site. Indirect immunofluorescence staining demonstrated that FK1 binds to the hippocampal neurons, as would be expected based on the high degree of homology among nAChR alpha subunits from diverse sources in the region surrounding Lys 125. PHY prevented the binding of FK1, thus supporting that FK1 is a specific probe for the PHY site. High-affinity sites (KD approximately 35 nM) for 1-methyl PHY were identified in hippocampal neurons. Similar to PHY, benzoquinonium (0.1 10 microM) and galanthamine (1-10 microM) activated nicotinic single channels. The agonists benzoquinonium and PHY were also open-channel blockers at the neuronal nAChRs, whereas galanthamine was predominantly a desensitizing agent. In mouse fibroblasts transfected with cDNAs of alpha 4 and beta 2 neuronal nAChR subunits, PHY also activated single channels that were blocked by FK1. In these cells, dihydro-beta-erythroidine blocked single channels activated by (+) anatoxin-a and did not affect those opened by PHY. Thus, the present results suggest that the novel agonist site located on the receptor alpha subunit is a common feature of neuronal nAChRs. PMID- 8510026 TI - Intrinsic properties of the nonpeptide angiotensin II antagonist losartan in glomeruli and mesangial cells at high concentrations. AB - Intrinsic activities of the nonpeptide angiotensin II antagonist losartan were examined in a number of in vitro assays. Losartan produced contraction of rat isolated glomeruli at 100 mumol/l and of human mesangial cells at 1 to 100 mumol/l. Cell surface reduction was associated with disorganization of the alpha actin microfilament bundles. Losartan also stimulated cytosolic calcium concentration in cultured human mesangial cells at high concentrations (10-100 mumol/l). Losartan-dependent cytosolic free calcium concentration increase was not affected by nicardipine or 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy benzoate hydrochloride, whereas it was abolished in a calcium-free medium. There was a marked homologous desensitization response to losartan which was also obtained after pretreatment by EXP 3174 (2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5 yl) biphenyl-4-yl)methyl]imidazole-5-carboxylic acid), the metabolite of losartan. The search for other agonistic effects of losartan in human mesangial cells including inositoltriphosphate formation, prostaglandin E2 production, [3H]leucine or [3H]thymidine incorporation was negative. Losartan and EXP 3174 were not toxic for human mesangial cells at the concentrations studied as judged by the absence of release of lactate dehydrogenase and the normal uptake of neutral red. These studies demonstrate that losartan exhibits glomerular effects in vitro only at high concentrations. Their relevance to in vivo situations is still questionable. PMID- 8510027 TI - [SN-FORTH/MSX: a state notation system for controlling behavioral experiments with a low-priced computer]. AB - A software system, SN-FORTH/MSX, has been developed to control behavioral experiments with a low-priced personal computer, MSX. Designed on the model of state notation, SN-FORTH/MSX enables researchers to program easily a wide variety of behavioral procedures including complex processes that are hard to describe with conventional programming languages such as BASIC and C. Since the real-time monitor of this system has a capability of parallel processing of multiple state sets, several independent experiments can be simultaneously conducted with a single computer. Users can observe and modify the working of real-time monitor in each instant with a set of run-time commands supplied in the system. PMID- 8510028 TI - Student voice: grief after abortion. PMID- 8510029 TI - Enhanced learning experience--a progressive clinical experience. PMID- 8510030 TI - TB on the rise in the U.S. PMID- 8510031 TI - Treatment of diabetes in the elderly. PMID- 8510032 TI - The unplanned lesson: students/instructor learn side by side. PMID- 8510033 TI - Business-education partnership. PMID- 8510035 TI - Student voice: who has the right to nursing care? PMID- 8510034 TI - Drug therapy in an aging population. PMID- 8510036 TI - Emergency room nurses: helping families cope with sudden death. PMID- 8510037 TI - Urinary tract infections caused by Candida species. PMID- 8510038 TI - What to do when ... the patient does not speak english! PMID- 8510039 TI - Understanding and managing Alzheimer's disease. PMID- 8510041 TI - Uncovering clinical knowledge and caring practices. AB - Narrative storytelling is a means by which knowledge embedded in nursing practice is uncovered and examined. Benner uses this method to study and explore skill acquisition and experience-based knowledge in nursing practice. By sharing these stories, knowledge that is unique to the experienced clinician is preserved and extended. The narrative presented here describes the expert coaching, discretionary judgment, and skilled involvement in the care of a patient in the PACU. PMID- 8510040 TI - How to keep patients happy when "all this work needs to be done!". PMID- 8510042 TI - Criteria for critiquing clinical nursing research reports. AB - The primary goal of nursing research is to develop a scientific knowledge base for practice. Postanesthesia nurses are expected to critique nursing research before applying findings to clinical practice. As consumers of research, postanesthesia nurses must be able to employ critical evaluation skills to judge the merit and relevance of research to their clinical practice. This article presents criteria for critiquing clinical nursing research reports to determine their relevance to practice. PMID- 8510043 TI - Practical points in understanding intravenous regional anesthesia. PMID- 8510044 TI - Caring for the ambulatory surgical patient who has a pacemaker: Part II- Intraoperative hazards and postoperative care. AB - Based on the content of this article, the reader should be able to: (1) describe the response of a pacemaker to an electromagnetic field; (2) state two sources of myopotential interference; (3) describe the relationship between monopolar and bipolar cautery and the risk of pacemaker function; (4) identify three types of pacemaker failures using an electrocardiogram rhythm strip; and (5) state two considerations when developing a discharge plan for an ambulatory surgical patient with a pacemaker. PMID- 8510045 TI - Critiquing research instruments for postanesthesia studies. AB - A recent series of articles instructed PACU nurses on steps in developing pencil and-paper instruments for research studies. What questions should PACU nurses ask when considering the use of existing pencil-and-paper instruments for use in research studies? The purpose of this article is to present nine steps in critiquing existing instrument before conducting research studies. Included are ethical considerations when using instruments and a checklist to assist PACU nurses in critiquing existing instruments. PMID- 8510046 TI - Establishing clinical competence in postanesthesia care nursing. AB - Today the manager in postanesthesia care is faced with the reality that basic nursing education and general nursing practice do not provide the specific body of knowledge required to prepare nurses to deliver competent nursing care for patients in the PACU phase I. This, in addition to the growing shortage of critical care nurses, the diminishing dollars available for education, and the massive amounts of knowledge being added almost daily to the basic knowledge base specific to the postanesthesia care area, requires the successful PACU manager to develop methods to select personnel with the highest success potential and to establish a competency-based, unit-specific education program to ensure individual success. PMID- 8510047 TI - Looking, feeling, watching, and seeing. AB - In today's hospital environment we often rely on technology for vital information about the status of our clients. This article is about looking and feeling (something technology cannot do for us). It is about simplicity and appreciating differences. PMID- 8510048 TI - Structure: a context for individual leadership. PMID- 8510049 TI - Poststructuralist historicism and the psychological construction of anxiety disorders. AB - When applied to the construction of anxiety disorders, theories of poststructuralist historicism emphasize acts of interpretation that constitute and construct the disorders and problematize the processes by which meaning is constructed. An examination of the historical formulations of anxiety disorders, and in particular, agoraphobia, provides the opportunity for reanalyzing traditional approaches to the classifications of disorders. Psychological issues of paradox, attachment, and personal identity, which are crucial to current conceptualizations of agoraphobia, are acutely problematized within a poststructuralist historicist hermeneutic. A rethinking of disorder construction from within this hermeneutic suggests replacing individualistic conceptualizations of personal identity with a broader view that recognizes and celebrates multiplicity and that displays formulations of the self in a contextualized and historicized status, thus enabling a fuller engagement with the social world. PMID- 8510050 TI - Psychoanalytic theory and loving God concepts: parent referencing versus self referencing. AB - We investigated the relationship of college students' conceptions of the wrathfulness-kindliness of God to their parents' nurturance, their parents' permissiveness, authoritarianism, and authoritativeness, and the students' own self-esteem. Although parents' nurturance, authoritarianism, and authoritativeness were related to participants' conceptions of God (thus providing some support for psychoanalytic assertions), the variable of self esteem far outweighed all other variables in accounting for the variance in God concepts. These results suggest that self-referencing explanations better account for individuals' conceptions of God than do parent referencing (i.e., psychoanalytic) explanations. PMID- 8510051 TI - Responsibility attributions for men and women giving sane versus crazy explanations for good and bad deeds. AB - We conducted two studies in which participants evaluated men and women who committed good or bad deeds and afterward gave crazy or sane explanations for their actions. In line with arguments of Thomas Szasz, people were evaluated as more mentally ill, having less intent, and taking little responsibility when they committed deeds that were bad rather than good; those giving crazy explanations for their actions were similarly judged. However, recommended prison sentences did not differ for people who gave crazy or sane explanations for their crimes. Data were integrated into a growing body of research investigating evaluations of criminal responsibility for people with psychological disorders. PMID- 8510052 TI - Detection of deception: a transactional analysis perspective. AB - I have attempted to integrate two divergent fields in applied psychology, the psychophysiological detection of deception (polygraph testing) and the transactional analysis theory. Transactional analysis theory provides a useful framework for understanding the examiner-examinee interaction in the pretest interview of the widely used but highly controversial control-question polygraph test. This research is relevant to the ongoing debate about the plausibility of the rationale underlying this technique. PMID- 8510053 TI - Loneliness and life satisfaction in Japan and Australia. AB - We examined the relationship between loneliness and life satisfaction in 121 residents of Fukoku, Japan, and 139 residents of Melbourne, Australia, using the Satisfaction With Life Scale (Diener, Emmons, Larsen, & Griffin, 1983) and the Revised UCLA Loneliness Scale (Russell, Peplau, & Cutrona, 1980). Australian subjects reported significantly less loneliness and significantly greater life satisfaction than Japanese subjects. A high inverse correlation was found between loneliness and life satisfaction in Australian subjects, with a much smaller inverse relationship observed among the Japanese, suggesting that loneliness in Japanese subjects did not emotionally translate into life dissatisfaction as it did in Australian subjects. Instead, the experience of loneliness in Japanese individuals may remain largely independent of general life satisfaction. PMID- 8510054 TI - Diurnal growth rhythms in the chicken eye: relation to myopia development and retinal dopamine levels. AB - 1. If the eyes of young chickens are deprived of clear vision by translucent occluders, they develop considerable amounts of axial myopia within days. At the same time, the day time retinal dopamine levels drop by about 30%. Because the retinal dopamine levels of normally sighted chicks also differ diurnally and are low at night, we expected that the rate of axial eye growth might also differ during this time. 2. Unexpectedly, eyes grew in length only during the day (about 0.13 mm/day) and even shrank during the night (about -0.04 mm/night, average net growth +0.09 mm in 24 h). 3. If the eyes were occluded, they grew both during the day and also at night (average net growth: +0.16 mm in 24 h). Therefore, development of deprivation myopia was a result of the lack of growth inhibition at night rather than of excessive growth during the day when the actual deprivation occurred. 4. Suppression of dopaminergic retinal pathways by intravitreal injections of the neurotoxin 6-hydroxy-dopamine (6-OHDA) also suppressed development of deprivation myopia and it restored the growth inhibition at night. With normal visual experience, the drug had no effect on axial eye growth and refractive state. 5. Diurnal growth rhythms of the eyes disappeared under continuous light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510055 TI - Wavelength-dependent effects of light on magnetic compass orientation in Drosophila melanogaster. AB - 1. Wildtype Oregon-R Drosophila melanogaster were trained in the ambient magnetic field to a horizontal gradient of 365 nm light emanating from one of the 4 cardinal compass directions and were subsequently tested in a visually symmetrical, radial 8-arm maze in which the magnetic field alignment could be varied. When tested under 365 nm light, flies exhibited consistent magnetic compass orientation in the direction from which light had emanated in training. 2. When the data were analyzed by sex, males exhibited a strong and consistent magnetic compass response while females were randomly oriented with respect to the magnetic field. 3. When tested under 500 nm light of the same quantal flux, females were again randomly oriented with respect to the magnetic field, while males exhibited a 90 degree clockwise shift in magnetic compass orientation relative to the trained direction. 4. This wavelength-dependent shift in the direction of magnetic compass orientation suggests that Drosophila may utilize a light-dependent magnetic compass similar to that demonstrated previously in an amphibian. However, the data do not exclude the alternative hypothesis that a change in the wavelength of light has a non-specific effect on the flies' behavior, i.e., causing the flies to exhibit a different form of magnetic orientation behavior. PMID- 8510056 TI - Discrimination of two-wavefront echoes by the big brown bat, Eptesicus fuscus: behavioral experiments and receiver simulations. AB - 1. Echolocating bats (Eptesicus fuscus) were trained to discriminate between simulated targets consisting of one or two echo-wavefronts with internal time delays of up to 100 microseconds. Spectral and temporal properties and total signal energy of the targets were evaluated and predictions for performances of bats derived from receiver models were compared with measured performances. 2. Eptesicus fuscus was able to discriminate a one-wavefront target from two wavefront targets with distinct internal time delays (12 microseconds, 32-40 microseconds and 52-100 microseconds). Performance was not affected by changes in total signal energy. Bats also successfully discriminated between two-wavefront targets with different internal time delays. 3. Performance predicted from differences in total energy between targets did not match the measured performance, indicating that bats did not rely on total echo energy. This finding is also supported by the behavioral data. Performance predicted from spectral and temporal receiver models both matched the measured performance and, therefore, neither one of these models can be favored over the other. 4. The behavioral data suggest that Eptesicus fuscus did not transform echo information into estimates of target range separation and, therefore, did not perceive the two wavefronts of each simulated two-wavefront echo as two separate targets. PMID- 8510057 TI - Recurrent uncomplicated urinary tract infection: a review of psychological factors. AB - Urinary tract infection (UTI) is a very common medical disorder among women, and is a chronic, recurrent problem for a cluster of sufferers. The factors involved in the aetiology of recurrent UTI are not adequately understood. Most research and treatment has focused on the influence of medical factors, although clinical impressions suggest that psychological factors (behavioural and personality variables) may play an important role. Evidence is reviewed for the involvement of psychological factors in the aetiology and treatment of recurrent UTI in women. It is difficult to draw any clear conclusions concerning the role of such factors in recurrent UTI, given the relatively small amount of research to date and a number of methodological issues. Suggestions for appropriate methodology and research concerning the interplay of physical and psychological factors are made. PMID- 8510058 TI - Sleep disturbance in chronic fatigue syndrome. AB - Sleep and fatigue characteristics were evaluated in 72 patients who met major criteria for the chronic fatigue syndrome (CFS), 57 multiple sclerosis (MS) patients preselected for fatigue complaints, and 40 healthy controls. Using previously validated rating scales, CFS patients had significant elevations in fatigue and sleep disturbance compared to the MS and healthy control groups. To confirm these subjective measures, polysomnography was carried out in a subgroup of CFS patients who included sleep disturbance as one of their symptoms on initial clinical interview. In 10 of 16 (62.5%) polysomnography revealed clinically significant and potentially treatable sleep abnormalities. Their sleep disorders included periodic movement disorder (4), excessive daytime sleepiness (3), apnea (2), and narcolepsy (1). We conclude that subjective sleep disturbance is common in CFS and some CFS patients may have objective sleep disorders. PMID- 8510059 TI - The relationship between information-seeking and information-avoiding coping styles and the reporting of psychological and physical symptoms. AB - The present paper describes a prospective study of the relationship between information-seeking and information-avoiding coping styles ('monitoring' and 'blunting') and the reporting of both psychological and physical symptoms. The results suggested that blunting was directly associated with the reporting of both psychological symptoms and symptoms associated with opportunistic infections (such as colds, 'flu etc.). Furthermore, this association between blunting and symptom report was independent of initial symptom levels and of some other factors which have been shown to influence health status (i.e. the frequency of negative life experiences, the frequency of daily hassles and levels of trait anxiety). No significant relationships were found between monitoring and symptom report. It is argued that the most likely explanation of these results is that high blunters report more illness symptoms as a result of failing to respond to initial illness cues or seeking remedial treatment only at a later stage in the development of a disorder. PMID- 8510060 TI - Physiologic benefits of a stress reduction program for healthy middle-aged Army officers. AB - Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD). This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients. PMID- 8510061 TI - Ischemic ECG changes are found more often in asymptomatic men with a coronary prone behaviour pattern. AB - Type A behaviour has been related to coronary heart disease (CHD) as an independent risk factor. Therefore, ischemic electrocardiographic (ECG) changes may be more prominent in Type A than in Type B individuals. ECG abnormalities were assessed by the Cardiac Infarction Injury Score (CIIS), which has predictive power for sudden death. In 100 healthy men aged 30-45 yr, the CIIS was related to cardiovascular risk factors such as age, blood pressure, smoking, family history of CHD and behaviour pattern groups defined by the Structured Interview (46 Type A, 20 Type X and 34 Type B subjects). The distribution of the CIIS was different among the behaviour pattern groups (p < 0.05) and was shifted towards higher ischemic scores in Type A subjects. These findings suggest that clinically asymptomatic persons with Type A behaviour have a greater probability of suffering ischemic heart disease and possible sudden death. PMID- 8510062 TI - Influence of perceived psychological stress and distress on antibody response to low dose rDNA hepatitis B vaccine. AB - The present study focused on the relationship between psychological stress and immune reaction to a novel antigen. Participants completed questionnaires on daily hassles, psychoneurotic complaints, coping style, and loneliness, 2 and 6 months after the first of a series injections with a low dose recombinant DNA hepatitis B vaccine. Antibody response was determined 7 months after the first vaccination. Based on the psychological questionnaires two different stress measures were calculated: a Stress Index score-month-2 and a Stress Index score month-6 indicating stress levels experienced at the beginning and at the end of the study respectively. Antibody levels were found to be negatively related with the Stress Index score-month-2. Although the influence of psychological stress reported on month 6 tended to be in the same direction, this effect was not significant. Coping styles and loneliness were not associated with antibody formation. These results suggest that antibody formation to rDNA hepatitis B vaccine is negatively influenced by psychological stress. PMID- 8510063 TI - Social functioning and general well-being in patients treated with clean intermittent catheterization. AB - Social role function, health perceptions and general well-being were studied longitudinally over 1 yr in 149 males and 153 females performing clean intermittent catheterization (CIC). The evaluation included urological assessments and self-rating instruments (Revised Physical Battery, General Health Questionnaire--28 items, State Anxiety Inventory and CIC Pain and Discomfort Scale). Twenty-six percent reported major improvement in their overall quality of life, while 7% reported a wish to be dead and away from it all. Females with infranuclear lesions and detrusor myopathies scored higher on unpleasant health perceptions, state anxiety and physical discomfort by performing CIC than males. In males, the social role function 1 yr later was predicted by initial anxiety and urinary tract infections, whereas in females by initial anxiety only. Discomfort by CIC was predicted by initial infection in males, and by none or moderate medical comorbidity, initial depression and infection in females. PMID- 8510064 TI - The long-term outcome of facial pain treatment. AB - The long-term outcome of facial pain treatment is largely unknown. This study reports the results of a 4-yr review which indicated that conservative treatments including drug therapy and counselling are effective for 70% of patients. Refractory pain was associated with a long complex history of pain, a preoccupation with physical symptoms and poor psychosocial adjustment. PMID- 8510065 TI - The impact of a 'guided self-help group' on bulimic women: a prospective 15 month study of attenders and non-attenders. AB - Bulimic women (N = 19) interested in a 'guided self-help group' were assessed by structured interviews and standardized tests. Eleven decided to attend the group, eight did not. Ten attenders (regular attendance of at least 6 months) and five non-attenders were followed for up to 6 months (mail questionnaires) and for 15 months (interviews) respectively. All the attenders and four non-attenders initially fulfilled DSM-III-R criteria for bulimia nervosa. After 15 months five attenders still met these criteria, whereas five improved to the point that they no longer did. Attenders showed significant improvement in specific psychopathology (drive for thinness, bulimia), general psychopathology (depression) and psychosocial adjustment, whereas non-attenders did not. However, three of five non-attenders also improved to a subclinical level, thus reflecting the natural course of the illness. Despite the small sample size our study indicates self-help as a valuable tool in overcoming an eating disorder. PMID- 8510066 TI - Key symptoms in the detection of affective disorders in medical patients. AB - Psychiatric disorder in medical patients often goes undetected. In this study we have attempted to identify a minimum set of key symptoms from an extensive research interview [Present State Examination (PSE)] that might assist in the identification of psychiatric disorders among general medical patients. Stepwise logistic regression analysis was used to identify PSE-items that contributed most to the PSE-CATEGO classification of psychiatric disorders in 192 Dutch medical out-patients. A risk score based on two core symptoms (panic and depressed mood) and five supplementary symptoms classified patients with a sensitivity of 0.94 and a specificity of 0.91. In a separate U.K. sample of medical in-patients, consisting of 37 PSE cases and age and sex matched controls, the risk score yielded a sensitivity and specificity of 0.89 and 0.97 respectively. The results suggest that a few questions concerning psychiatric symptoms may facilitate the identification of the majority of patients with anxiety and depressive disorders in medical populations. PMID- 8510067 TI - Abnormal extracranial vasomotor response in migraine sufferers to real-life stress. AB - Temporal and digital pulse amplitudes, forehead temperature, heart rate, respiration rate and electrodermal activity of 37 migraine patients and 37 matched controls from a population of psychology students were recorded during three experimental sessions: adaptation, real-life stress (an examination) and experimental stress (an IQ test). Migraine sufferers showed significantly smaller pulse amplitudes of the temporal artery during the examination than the control group. No group differences were present in the other physiological measures. The findings are interpreted as indirect evidence for the symptom specificity hypothesis, which states that individuals with specific psychosomatic complaints display abnormal responses to stress in the relevant physiological system. PMID- 8510068 TI - Attitudes and prognosis in chronic low back pain. AB - Eighteen patients with chronic low back pain were interviewed before and after a programme of conservative treatment and again 4 months later. Measures were made of severity and attitude towards disability, including the Kelly Repertory Grid. The best predictor of improvement was the degree of meaningfulness of the concept 'self in pain' as measured by the Repertory Grid. PMID- 8510069 TI - Anxiety, attention and pain. AB - In a within-subject design the hypothesis was tested that focus of attention rather than anxiety influences pain. Twenty-four spider phobics received a moderately painful electrical stimulation in each of four conditions: low anxiety/attention directed towards pain; low anxiety/attention distracted from pain; high anxiety/attention directed towards pain; high anxiety/attention distracted from pain. Anxiety was induced by means of exposure to a spider. Subjective pain ratings strongly supported the hypothesis: pain was rated lower when the subject diverted attention away from than when the subject attended to the pain stimulus, regardless of level of anxiety. The Skin Conductance Response to the first pain stimulus of the series of four in each condition was, however, higher when the subject distracted than when the subject attended to the pain stimulus. There were no experimental effects on later Skin Conductance Responses. Most importantly, there was no influence of anxiety on any of the pain responses. Attentional focus rather than anxiety per se seems to influence pain. PMID- 8510070 TI - Solubilization and characterization of motilin-receptor complexes from rabbit antral smooth muscle tissue. AB - In the present study, the motilin receptor was characterized by enzymatic digestion studies and by solubilization of the motilin-receptor complex from prelabeled membranes using the anionic detergent cholic acid. Motilin binding was significantly decreased by preincubation of membranes of rabbit antral tissue with trypsin, phospholipase A2, C, D, dithiothreitol and 2-mercaptoethanol but not by neuraminidase and beta-galactosidase. Treatment of prelabeled membranes with 1% cholic acid resulted in solubilization of 24 +/- 5% of the proteins and 65 +/- 3% of the radioactivity. The latter was for 77 +/- 4% due to the presence of the motilin-receptor complex as estimated with PEG-precipitation. Upon gel filtration on Superose 6 the complex partially dissociated but 43 +/- 3% eluted with macromolecular components in the void volume. This peak was not detected when membranes were first incubated with unlabeled motilin. Further disaggregation was accomplished by the addition of 0.5 M NaCl to the elution buffer. The chromatographic profile then showed a peak of about 370 kDa and a second one of 100 kDa. The latter value probably reflects the molecular mass of a single 125I-motilin-receptor-complex. PMID- 8510071 TI - Solubilization and characterization of high affinity follicle-stimulating hormone receptors from porcine granulosa cells. AB - Follicle-stimulating hormone (FSH)-receptors were solubilized from immature porcine ovarian granulosa cells with retention of high affinity 125I-porcine FSH binding activity. The optimal concentration of Triton X-100 for solubilization was 0.5% (w/v), and the optimal cellular protein concentration 25 mg/ml. Glycerol (30%) increased recovery of solubilized receptor. 125I-pFSH-binding affinity ranged from 4 x 10(10) M-1 to 8 x 10(10) M-1 in either the absence or presence of glycerol. 125I-pFSH-binding capacity was 5 fmol/mg protein in the absence of glycerol and 58 fmol/mg protein in the presence of glycerol as determined by equilibrium saturation binding analysis. By gel permeation chromatography, the apparent size of the 125I-pFSH-receptor complex was 462 kDa in the absence of glycerol and 762 kDa in the presence of glycerol. Ligand blotting of solubilized receptor yielded a single species with an apparent molecular weight of 200 kDa under nonreducing conditions and a single species with an apparent molecular weight of 60 kDa under reducing conditions. These studies indicated that high affinity FSH-binding activity can be solubilized from membranes of immature porcine granulosa. PMID- 8510072 TI - Primary culture of canine tracheal smooth muscle cells in serum-free medium: effects of insulin-like growth factor I and insulin. AB - The effects of growth factors on cell growth and muscarinic receptor (mAChR) expression of canine tracheal smooth muscle cells (TSMCs) were observed under serum-free medium supplemented with 0.1% BSA. In the presence of 0.1% BSA, TSMCs withdraw from cell cycle as compared with 10% FBS and allow to determine the effects of growth factors on mAChR expression. The individual components of growth factors (IGF-I, insulin, and aFGF) at the concentration used are not sufficient to stimulate growth of TSMCs in the primary culture with 0.1% BSA. IGF I (10 ng/ml) and insulin (1 microgram/ml), alone or in combination, could stimulate the expression of mAChRs of cultured TSMCs. Heparin could inhibit these stimulatory effects of mAChR expression. The stimulatory effects of IGF-I and insulin on mAChR expression were mediated through their own receptors since these effects were reversed by pretreatment of TSMCs with antibodies of the respective growth factor receptors. The pharmacological response of functional mAChRs, determined as accumulation of inositol phosphates induced by carbachol, is greater in the medium containing IGF-I and insulin than that cultured in 0.1% BSA. These results firmly establish that IGF-I and insulin could stimulate the expression of mAChRs in TSMCs under serum-free culture condition. PMID- 8510073 TI - Solubilization and characterization of the A2-adenosine receptor. AB - Binding of [3H]CGS 21680, an agonist radioligand selective for A2-adenosine receptors (A2AR), to membranes and solubilized preparations from bovine brain striatum revealed labelling of a single high affinity binding state. In membranes, guanine nucleotides per se were ineffective in modulating agonist binding whereas cations, Na+ and Mg++, had distinct effects. The addition of NaCl (200 mM) as well as the Mg(++)-free preparation of membranes led to a significant decrease in binding affinity and the number of binding sites. Moreover, the presence of Na+ was required for the demonstration of a guanine nucleotide effect, i.e. a decrease in maximal binding. Following solubilization, agonist A2AR interactions were sensitive to guanine nucleotides even in the absence of Na+; guanine nucleotides and Na+ had additive effects in reducing the number of binding sites. Moreover, the effect of GTP was reversible, i.e. binding returned to control levels upon removal of the nucleotide. This suggests the A2AR and its G protein (presumably Gs) are solubilized as a functional unit and may not dissociate even in the presence of GTP following solubilization. We, therefore, believe that a "tight" association exists between receptor and G protein (Gs), and that guanine nucleotides and sodium act at different sites on the R-G complex. Drawing an analogy with similar observations on the avian beta adrenergic receptor (Hertel et al, J. Biol. Chem. 265:17988-94, 1990; Parker & Ross, J. Biol. Chem. 266:9987-96, 1991) we postulate that the regulatory features of the A2AR can be attributed to a distinct receptor domain that interacts with cellular regulatory elements. PMID- 8510074 TI - Amino acid residues within the sequence region alpha 55-74 of Torpedo nicotinic acetylcholine receptor interacting with antibodies to the main immunogenic region and with snake alpha-neurotoxins. AB - The sequence region 55-74 of the alpha-subunit of the acetylcholine receptor (AChR) from Torpedo californica electroplax comprises the amino-terminal end of a sequence segment--residues alpha 67-76--forming the main immunogenic region (MIR), which is most frequently recognized by anti-AChR autoantibodies in myasthenia gravis. The synthetic sequence alpha 55-74 of Torpedo AChR binds alpha bungarotoxin (alpha BTX), suggesting that amino acid residues within this sequence region may contribute to formation of an alpha BTX binding site. Using single-residue substituted synthetic analogues of the sequence alpha 55-74 of Torpedo AChR, in which each residue was sequentially substituted by either glycine or alanine, we sought identification of the amino acids involved in interaction with alpha-neurotoxins and with three different anti-MIR monoclonal antibodies (mAbs 6, 22, and 198). Substitution of Arg55, Arg57, Trp60, Arg64, Leu65, Arg66, Trp67, or Asn68 strongly inhibited alpha-toxin binding, whereas substitutions of Ile61, Val63, Pro69, Ala70, Asp71, or Tyr72 had marginal effects. Substitutions within the region alpha 68-72 significantly diminished binding of anti-MIR mAbs, although residue preferences differed among mAbs. Further, substituting Trp60 substantially reduced binding of mAb 198, and moderately affected binding of mAb 6, and substitution of Asp62 slightly but consistently affected binding of mAbs 6 and 22. PMID- 8510075 TI - Immunomodulation of cellular cytotoxicity to herpes simplex virus infection in pregnancy by inhibition of eicosanoid metabolism. AB - In an effort to evaluate the relationships among pregnancy, cellular cytotoxicity and herpes simplex virus (HSV) infection, we conducted a series of experiments investigating: (1) the maternal cellular cytotoxic response to HSV infection as compared with non-pregnant hosts, (2) the influence of both cyclooxygenase and lipoxygenase products on cytotoxicity by selective inhibition of their metabolic pathways, and (3) the potential pregnancy-related differences in immune response to selective inhibition of eicosanoid metabolism. Indomethacin was used for cyclooxygenase blockade and nordihydroguaiaretic acid was used to evaluate lipoxygenase inhibition. In the non-infected animals no differences in cytotoxicity were observed between pregnant (1.5% +/- 0.7%) and non-pregnant (4.6% +/- 2.0%) groups. HSV infection increased cytotoxicity equally in both groups (pregnant: 10.6% +/- 2.0% vs. non-pregnant: 14.2% +/- 3.4%). Indomethacin did not significantly alter cytotoxicity in either the pregnant or the non pregnant groups compared with controls (12.8% +/- 1.8% vs. 10.6% +/- 2.0% and 14.3% +/- 3.9% vs. 14.2% +/- 3.4%, respectively). In contrast, NDGA elicited a significant reduction in the cytotoxic response in both pregnant and non-pregnant hosts (6.2% +/- 1.1% vs. 10.6% +/- 2.0% and 5.7% +/- 1.1% vs. 14.2% +/- 3.4%, respectively). From our study we conclude that: (1) cytotoxicity is maintained at low levels in the absence of HSV infection, (2) HSV infection induces a significant augmentation in host cellular cytotoxicity, (3) pregnant and non pregnant cytotoxic responses to HSV infection appear comparable, (4) indomethacin does not augment in vitro cytotoxicity to HSV infection and (5) NDGA suppresses cytotoxicity, providing evidence that lipoxygenase metabolites are essential to cytotoxic cell function. PMID- 8510077 TI - Inhibitory effect of choriocarcinoma-derived high molecular weight factor (HMWF) on lymphocyte proliferation and adhesion to trophoblasts. AB - Trophoblast-secreted soluble factors may deter the immune rejection of the fetus which can occur from interaction between maternal lymphocytes and fetal trophoblasts in decidua. The effect of size-fractionated culture fluid of choriocarcinoma cells on the function of lymphocytic cells was studied. The results show that dialyzed soluble factor (HMWF) of molecular weight > 100 kDa was inhibitory to lymphocyte proliferation in a dose-dependent manner and prevented lymphocyte-to-trophoblast adhesion in a similar fashion. The effect was abrogated by a freezing-thawing process and heat treatment. Similarly, the fractions below 100 kDa size had no effect on lymphocyte functions. Although the nature of HMWF is not yet known, it appears that this factor differs from most of the well-characterized pregnancy factors but is similar to the recently described high molecular weight factor found in primary cultures of trophoblasts and choriocarcinoma lines. The inhibitory effect of trophoblast-derived HMWF on cell contact-based immune recognition may contribute to maternal tolerance. PMID- 8510076 TI - West Nile virus infection induces susceptibility of in vitro outgrown murine blastocysts to specific lysis by paternally directed allo-immune and virus-immune cytotoxic T cells. AB - Day 3 post-coitum BALB/c and (BALB/c x CBA/H)F1 blastocysts were isolated and hatched in replicate wells. Some were treated with interferon-gamma (IFN-gamma). Whilst others were infected with West Nile Virus (WNV) at 100 plaque-forming units per cell, for 18 h. Controls were mock-treated. Gamma-irradiated (2000 rads) CBA/H, (paternal) WNV-specific and allo(CBA/H)-specific cytotoxic T (Tc) cells were then added to replicates of infected, mock-infected or IFN-gamma treated cultures for 20 h. [3H]Thymidine was then added for a further 8 h. [3H]Thymidine incorporation was inhibited by 40-50% in WNV-infected cultures exposed to WNV-paternal-specific Tc cells and by 30-40% in WNV-infected cultures exposed to allo-paternal-specific Tc cells compared to similarly exposed, uninfected, or unexposed, WNV-infected, or unexposed, uninfected cultures. No significant differences in [3H]thymidine incorporation were found between these controls and IFN-gamma-treated cultures exposed to allo-paternal-specific Tc cells or IFN-gamma-treated cultures not exposed to Tc cells. Parallel exposure of L929 fibroblasts to the same Tc cells irradiated with 500-8000 rads in doubling doses, showed that irradiation did not alter the efficacy or specificity of the Tc cells. Relevance to maternal anti-viral immune responses during implantation is discussed. PMID- 8510078 TI - Tolerance of sheep-goat chimeras to their component cells. AB - Four sheep-goat chimeras with a goat or sheep sibling having an identical genotype to one of the two component species of cells were tested for tolerance through mixed lymphocyte response (MLR) and skin grafts. None of the four chimeras showed a response to its sib in MLR and three of the four accepted sib skin grafts. This demonstrates that the chimerism exhibited by these animals was sufficient to render the chimera tolerant to antigens expressed by the sib. Two of the four sibs showed positive responses to their chimeric sibs in MLR and two did not; one negative response was expected because the chimera's lymphocytes were essentially all the same species as the sib's. Chimeric skin grafts were partially accepted by two of the four sibs, suggesting the presence of both sheep and goat cells in the skin grafts derived from the chimeras. Two of the four sibs did not accept chimeric skin grafts, possibly due to lack of compatible cells in the graft. Neither differences between an allo- and xenoresponse in MLR nor time differences in the rejection of allo- and xenografts were observed. PMID- 8510079 TI - AJ-p90: a novel protein of the perinuclear theca in human sperm subacrosome. AB - A perinuclear theca protein of the human sperm subacrosome was detected using LH43 monoclonal antibody which was originally raised against human keratinocytes. Using indirect immunofluorescence, the antibody stained the acrosomal zone (AZ) of dried ejaculated spermatozoa but did not react with viable cells, thus suggesting that the antigen was intracellular. This was confirmed by immunogold electron microscopy which also revealed the ultrastructural localisation of the antigen to the subacrosomal fibrils. Throughout spermatogenesis the antigen was only detected on the AZ of developed testicular spermatozoa and its expression was continued during their epididymal passage. Biochemically, the protein was insoluble in Triton, and dithiothreitol (DTT) was required for its solubilisation. In Western blotting of sperm and keratinocyte lysates, the antibody detected similar 90-kDa protein doublets (AJ-p90). These biochemical features exclude the identity of AJ-p90 with various cyto- and karyo-skeletal antigens, including the intermediate filaments and microfilaments. AJ-p90 therefore represents a novel product of the subacrosomal perinuclear theca. The significance of these data is discussed together with the importance of the antibody for probing the perinuclear theca in normal and abnormal germ cells, including multinucleated spermatids which also showed reactivity with the antibody. PMID- 8510080 TI - Usefulness of synthetic Mimetic ligands in establishing an affinity chromatography procedure for purifying estradiol antibody in sheep serum: potential application in regulating fertility of the ram. AB - Recently developed synthetic Mimetic affinity ligands were screened for their ability to purify estradiol antibody from sheep serum. One of these ligands (color coded Yellow 1) effectively separated immunoglobulin from other serum protein by negative affinity. When 1 ml antiserum diluted 70% (protein content approximately 25 mg) was passed through 1 ml gel with Yellow 1 ligand, estradiol antibody-binding activity (% binding of E2 tracer) peaked in the effluent (62%) and decreased progressively in the subsequent three 4-ml fractions of the wash (34%, 6% and 2%, respectively). As long as the total amount of serum protein applied remained below the saturable-binding capacity of the ligand (determined to be approximately 28 mg), the relative purity of estradiol antibody in the effluent (E2 binding per unit protein) remained very high with only 3% (0.78 mg) of applied protein appearing in the effluent. Purity of antibody in the effluent was confirmed by electrophoresis carried out on SDS polyacrylamide gel. Flow rate of serum diluted 42% (1 ml, protein content approximately 48 mg) was constant and acceptable (0.37 ml/min) and uncoupling of nonimmunoglobulin serum protein from the ligand was complete by the time the column was reequilibrated. We conclude that of the different Mimetic ligands evaluated Yellow 1 has properties that would be useful in a large-scale affinity chromatography procedure for purifying immunoglobulin from sheep serum. PMID- 8510082 TI - LAM 100/Marshall F-88: accuracy and precision of a new device for discontinuous finger blood pressure measurement. AB - We tested the performance of the LAM 100 (also known as the Marshall F-88), a semiautomated oscillometric device for discontinuous BP measurement at the finger, which could be very suitable for self-recording of BP because of its small size and convenient mode of operation. The LAM 100 was compared with the random zero sphygmomanometer and with BP measured by the Finapres for beat-to beat measurement of finger arterial pressure in 40 patients following guidelines of the AAMI. Compared with the random zero sphygmomanometer the LAM 100 underestimated SBP by 9 mmHg (SD 12) and DBP by 7 mmHg (SD 9). These differences exceed the limits set by the AAMI. The differences between the LAM 100 and the random zero spghymomanometer could not be explained by physiological peripheral pulse wave changes because Finapres SBP was underestimated by 4 mmHg (SD 15) and DBP was overestimated by the LAM 100 by 8 mmHg (SD 10). We conclude that the LAM 100 is not suitable for the diagnosis and management of hypertension. PMID- 8510081 TI - von Willebrand factor and endothelial damage in essential hypertension. AB - The relationship between von Willebrand factor antigen (vWFAg, a specific endothelial cell product) and hypertension was examined. Circulating vWFAg levels were measured in serum from patients attending a hypertension clinic and in normotensive controls. The vWFAg was higher in those patients with uncontrolled hypertension at 131 +/- 34 IU/dl than in controls (90 +/- 30 IU/dl) and in those whose hypertension was controlled 104 +/- 29 IU/dl (P < 0.001). Levels of vWFAg correlated with both SBP (r = 0.42, P < 0.0002) and DBP (r = 0.25, P < 0.05), but serum from neither group of patients was more cytotoxic to cultured endothelial cells in vitro than was serum from controls. Neither symptoms of cardiovascular or peripheral vascular disease or two of its risk factors (hypercholesterolaemia or smoking, alone or in combination) appeared to further increase vWFAg in patients with uncontrolled hypertension. However, vascular disease and the same risk factors did increase vWFAg to 133 +/- 36 IU/dl in those patients with controlled hypertension (P < 0.001). These data indicate a relationship between vWFAg and hypertension and suggest that endothelial damage may indeed be important in the vascular complications of hypertension. PMID- 8510083 TI - Cognitive function in hypertension: a community based study. AB - Cognitive function was investigated in a random sample of subjects on the general practitioners' registry of hypertensive patients in an inner city area and matched with normotensive controls. The response rate was 66% giving 90 matched pairs, average age 63 yrs, with 47% men. There was no difference in educational background or measures of reading ability between the two groups. Cognitive function tests showed a consistent trend of poorer performance in hypertensives, with significant differences in Verbal Learning (immediate recall and retention). Age was inversely related to cognitive function, but no additional deterioration with increasing age was shown in hypertensives. PMID- 8510084 TI - Regression of vascular structural changes and calcium metabolism in patients with essential hypertension after long-term monotherapy with enalapril. AB - We investigated the effect of one year of enalapril monotherapy on vascular structural changes and calcium metabolism in ten patients with essential hypertension. BP decreased from 169-10/103 +/- 10 mmHg during the placebo period to 138-12/82 +/- 10 mmHg after enalapril therapy. Minimal vascular resistance assessed by the venous occlusion technique with strain-gauge plethysmography was higher in the hypertensive patients than in the normotensive subjects (2.7 +/- 1.2 vs. 1.2 +/- 0.3 mmHg/ml/min per 100 ml tissue, P < 0.01). Although the elevated minimal vascular resistance seen in essential hypertensives decreased to 1.7 +/- 0.5 mmHg/ml/min per 100 ml tissue after enalapril (P < 0.01), it remained higher than that of normotensives (P < 0.05). Cytosolic free calcium ([Ca2+]i) in platelets measured by a Qiun-2 fluorescent indicator was higher in essential hypertensives than in normotensives (189 +/- 38 nM and 138 +/- 14 nM, respectively; P < 0.01). [Ca2+]i of essential hypertensives was reduced to 138 +/ 19 nM after treatment. Plasma renin activity was significantly increased after enalapril. Although plasma ionized calcium concentration did not change, parathyroid hormone was significantly increased after enalapril (from 0.36 +/- 0.22 to 0.58-0.32 ng/ml, P < 0.05). During the placebo period, minimal vascular resistance was correlated with [Ca2+]i (r = 0.62, P < 0.01). There was a close relationship between the changes in minimal vascular resistance and [Ca2+]i (r = 0.78, P < 0.01); however the change in minimal vascular resistance was not associated with changes in BP, catecholamine or parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510085 TI - Investigation of high salt intake in a Nepalese population with low blood pressure. AB - The relation between BP and the factors influencing an increase in BP with age were investigated in the inhabitants of two representative hilly (Kotyang: 206 men and 212 women) and suburban (Bhadrakali: 265 and 244) villages in Nepal. BP for both sexes was statistically significantly higher in Bhadrakali than in Kotyang. Neither hypertension nor elevation of BP with age for men and very few women (1.4%) with hypertension were observed in Kotyang, while 10.9% of men and 4.9% of women were found to be hypertensive in Bhadrakali. Average urinary Na excretion was 183-221 mEq/day in both villages. Urinary Na/K ratio, percentage body fat (%Fat), total protein, total cholesterol and serum Ca were statistically significantly higher in Bhadrakali than in Kotyang, and maximal oxygen uptake and serum Mg were higher in Kotyang. In spite of high salt consumption, there was no increase in BP with age in Kotyang's males, suggesting that the BP may be influenced by physical activity, fat-free mass and nutrient consumption in addition to the high sodium intake, and that extremely high physical activity and very low %Fat could serve to mute the influence of high sodium intake. PMID- 8510086 TI - Comparison of the efficacy and metabolic effects of nicardipine and hydrochlorothiazide in hypertensive black men and women. AB - A double-blind, randomised, parallel study compared the BP and metabolic responses in black hypertensive patients following monotherapy with nicardipine or hydrochlorothiazide (HCTZ). Following a single-blind placebo wash-out period of 1-4 weeks, the study drug, nicardipine 20-40 mg three times daily or HCTZ 25 100 mg four times daily, was administered in a double-blind fashion for 12 weeks. Doses were titrated to control sitting DBP (< or = 90 mmHg). Both drugs were effective in reducing sitting SBP and DBP as compared with baseline values (nicardipine: 152.5 +/- 1.6/102.0 +/- 0.6, HCTZ: 152.5 +/- 1.5/101.4 +/- 0.5 mmHg). DBP responses (reduction from baseline; nicardipine: -10.9, HCTZ: -12.7 mmHg), and the percentage of patients achieving a response < or = 90 mmHg (nicardipine: 54%, HCTZ: 63%) to the two drugs were similar. Although SBPs at baseline and endpoint (137.3 +/- 1.6 on nicardipine and 132.1 +/- 1.4 mmHg on HCTZ), and the percentage of patients achieving a response < or = 140 mmHg (nicardipine: 70%, HCTZ: 79%), were comparable between the two treatments, the SBP reduction with HCTZ was statistically greater (P = 0.026). A comparison of the metabolic responses in the two treatment groups showed significant differences. Nicardipine caused no significant changes in blood chemistry, whereas HCTZ caused statistically significant decreases (P < 0.001) in sodium and potassium and increases (P < or = 0.01) in glucose, BUN, creatinine, uric acid, cholesterol and LDL compared with baseline. In 12.7% of the patients in the HCTZ group, serum potassium dropped to levels < 3.5 meq/l, which occurred in only 1.4% of the patients who used nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510087 TI - Influence of combination of captopril and hydrochlorothiazide on plasma lipids, lipoproteins and apolipoproteins in primary hypertension. AB - The effects of the combination of captopril and hydrochlorothiazide at modest doses of plasma lipids, lipoproteins and apolipoproteins were investigated in 139 patients with mild to moderate primary hypertension. Following an eight week wash out period and a 4 week period of monotherapy with either captopril or hydrochlorothiazide, the combination of captopril 50 mg and hydrochlorothiazide 25 mg daily was given for 16 weeks. All factors known to affect plasma lipids were held constant throughout the study (i.e. diet, weight, exercise, caffeine, tobacco). There were significant reductions in total and low density lipoprotein cholesterol (P < 0.01), total cholesterol/high density lipoprotein-cholesterol (P < 0.001) and low density lipoprotein/high density lipoprotein-cholesterol (P < 0.01) ratios. These favourable changes were significant only in patients whose baseline values were above the 90th centile adjusted for age and sex. The combination had a neutral effect on plasma lipids in patients with normal values. The data suggest that the combination of captopril and hydrochlorothiazide at modest doses does not induce deleterious changes in lipid profile and warrant further long-term controlled studies. This antihypertensive regimen may thus represent an advantageous alternative in subjects with a potentially atherogenic lipoprotein profile. PMID- 8510088 TI - Double-blind controlled study of rilmenidine versus hydrochlorothiazide in mild hypertension: clinical and renal haemodynamic evaluation. AB - Clinical and renal haemodynamic parameters were evaluated in 20 mild hypertensive patients after rilmenidine (RIL) administration during a one month double-blind randomised study compared with hydrochlorothiazide (HCT). At the beginning and at the end of the study, BP, heart rate and renal haemodynamic parameters were evaluated. Renal haemodynamic parameters included effective renal plasma flow (ERPF) evaluated by radionuclide study utilising 131I-Hippuran according to Schlegel's method, effective renal blood flow (ERBF = ERPF/(1-Ht)), glomerular filtration rate (GFR) by creatinine clearance, filtration fraction (FF = GFR/ERPF) and renal vascular resistances (RVR = DBP x 80/ERBF). RIL and HCT significantly (P < 0.01) reduced systolic, diastolic and mean blood pressure without relevant change in ERPF, ERBF, GFR and FF. RVR was significantly reduced both in the RIL group (P < 0.002 vs. baseline) and in the HCT group (P < 0.001 vs. baseline). No relevant side-effects were observed in either group. In conclusion, rilmenidine was effective in reducing BP in mild hypertensive patients and produced favourable effects on renal function. PMID- 8510089 TI - Nonpharmacological interventions as an adjunct to the pharmacological treatment of hypertension: a statement by WHL. The World Hypertension League. AB - Nonpharmacological approaches lower medication requirements in patients with hypertension. A decreased salt intake to a sodium value of about 80 mmol/day lowers BP in the presence of diuretics, beta-blockers, converting enzyme antagonists and sympatholytics but apparently not in patients treated solely with calcium antagonists. A reduced medication requirement is seen in about half of the patients suggesting that the phenomenon of 'salt-sensitivity' still applies. Weight loss is an effective adjunctive therapy and simultaneously improves other cardiovascular risk factors. A high alcohol consumption is a confounding factor in the drug treatment of hypertension. Reducing the alcohol intake of hypertensive heavy drinkers significantly lowers their BPs and drug requirements. Aerobic exercise is an effective nonpharmacological treatment which simultaneously fosters weight loss and improves risk factors. Potassium supplementation does not decrease medication requirements in drug-treated patients who are ingesting a low salt diet but may do so in those eating large amounts of salt. Nonpharmacological approaches should be included in the management of all hypertensive patients irrespective of their drug therapy. These should include weight reduction through decreased food and alcohol consumption as well as regular, programmed exercise. Patients should be instructed in a low calorie diet rich in fresh rather than processed products and high in fruits and vegetables. Such a diet will contain relatively little salt, reduced fat, and ample amounts of potassium and calcium. However, physicians should not lose sight of the fact that cigarette smoking remains the most important risk factor to be addressed in their hypertensive patients. PMID- 8510090 TI - Elucidating the genetic basis of spontaneous hypertension: a perspective. PMID- 8510091 TI - Does the kidney play a role in the aetiology of primary hypertension? Evidence from renal transplantation studies in rats and humans. AB - In renal cross-transplantation studies between four different strains of genetically hypertensive rats including Dahl salt-sensitive hypertensive rats, Milan hypertensive rats, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) on the one hand and their respective normotensive control strains on the other hand, it was found that BP determinants were carried within the kidney. To determine whether post-transplantation hypertension in recipients of an SHRSP kidney was due to a primary or secondary defect in the renal graft, hypertension in SHRSP kidney donors was prevented by chronic antihypertensive drug treatment. Despite sustained BP normalisation in SHRSP kidney donors, the recipients developed post-transplantation hypertension. This finding indicates that SHRSP kidneys carry a primary defect which can elicit hypertension. F1 hybrids bred from SHRSP and normotensive Wistar-Kyoto rat (WKY) parents show an age-related increase in arterial BP up to borderline hypertensive levels. Renal transplantation studies in young rats indicate that the development of borderline hypertension in (SHRSP x WKY)-F1 hybrids can be blunted by bilateral nephrectomy and transplantation of a WKY kidney. Clinical studies in human renal transplant patients also indicate that the genetic background of the kidney donor with respect to predisposition for genetic hypertension significantly influences BP and/or the need for antihypertensive medication in the recipients. Together, the results of renal transplantation studies in animals and humans suggest that a genetic defect in the kidney plays a major role in the pathogenesis of primary hypertension. PMID- 8510092 TI - Investigations of isolated small arteries from patients with hypertension. PMID- 8510093 TI - Arteriolar reactivity to ouabain and antidigoxin antibody in hamster microcirculation. PMID- 8510094 TI - Effect of local intra-arterial asymmetric dimethylarginine (ADMA) on the forearm arteriolar bed of healthy volunteers. PMID- 8510095 TI - Health effects of environmental exposure to cadmium in a population study. AB - The Cadmibel Study is a cross-sectional population study, which investigated the hypothesis that environmental exposure of the population to cadmium would result in health effects. The 2,327 participants constituted a random sample of the population of four Belgian districts, chosen to provide a wide range of environmental exposure to cadmium. The urinary cadmium excretion, a measure of lifetime exposure, averaged 9.3 nmol/24h in men (range 0.4-325 nmol/24h) and 7.2 nmol (0.1-71 nmol/24h) in women. The Cadmibel Study refuted the hypothesis that exposure to cadmium would lead to an increase in BP and in the prevalence of hypertension and other cardiovascular diseases. Serum alkaline phosphatase activity and the urinary excretion of calcium correlated significantly and positively with urinary cadmium in both sexes. These findings suggest that the calcium metabolism is gradually affected, as cadmium accumulates in the body. Furthermore, several markers of renal tubular function (urinary excretion of retinol binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin and aminoacids) were significantly and positively associated with urinary cadmium. There was a 10% probability of abnormal values of these markers of tubular function when urinary cadmium exceeded +/- 20 nmol/24h. However, the morbidity associated with the functional changes, observed in the Cadmibel Study, remains presently unknown and requires further investigation, preferably in a longitudinal population studies. PMID- 8510096 TI - SYST-EUR multicentre trial on the treatment of isolated systolic hypertension in the elderly: first interim report. PMID- 8510097 TI - Leg/arm diastolic ratio. PMID- 8510098 TI - GroupBuild: a fragment-based method for de novo drug design. AB - A novel method for de novo drug design, GroupBuild, has been developed to suggest chemically reasonable structures which fill the active sites of enzymes. The proposed molecules provide good steric and electrostatic contact with the enzyme and exist in low-energy conformations. These structures are composed entirely of individual functional groups (also known as "building blocks" or "fragments") which the program chooses from a predefined library. User-selected enzyme seed atom(s) may be used to determine the area(s) in which structure generation begins. Alternatively, GroupBuild may begin with a predocked "inhibitor core" from which fragments are grown. For each new fragment generated by the program, several thousand candidates in a variety of locations and orientations are considered. Each of these candidates is scored based on a standard molecular mechanics potential function. The selected fragment and orientation are chosen from among the highest scoring cases. Tests of the method using HIV protease, FK506 binding protein, and human carbonic anhydrase demonstrate that structures similar to known potent inhibitors may be generated with GroupBuild. PMID- 8510099 TI - Transformation of monoamine oxidase-B primary amine substrates into time dependent inhibitors. Tertiary amine homologues of primary amine substrates. AB - A family of N-methylated and N,N-dimethylated alkyl and arylalkylamines was prepared and more than half of the analogues were shown to be time-dependent pseudo-first-order inhibitors of monoamine oxidase-B. Some of the time-dependent inactivators were reversible and others were irreversible with respect to prolonged dialysis following inactivation. Partition ratios ranged from zero to 11,000. These results are rationalized in terms of a combination of an inductive effect and a stereoelectronic effect as a result of hindered rotation of an active site covalent adduct. A molecular mechanics calculation indicates that there is at least 10 kcal/mol of torsional energy to be overcome in order for the enzyme adduct to be released. These findings show that tertiary amine homologues of primary amine substrates of monoamine oxidase are time-dependent inhibitors, and this should be useful in the design of new inactivators of this enzyme. PMID- 8510100 TI - The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3 butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate. AB - A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2 (diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptosomes was determined for each compound. It was found that the most potent examples are those having a substituent in an "ortho" position in one or both aromatic/heteroaromatic groups. The majority of the compounds described are structurally related to tiagabine, (R)-1-[4,4-bis(3-methyl-2 thienyl)-3-butenyl]-3- piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized. PMID- 8510101 TI - Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1 ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists. AB - A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure activity relationship data are described. PMID- 8510102 TI - Structure, DNA minor groove binding, and base pair specificity of alkyl- and aryl linked bis(amidinobenzimidazoles) and bis(amidinoindoles). AB - A series of bis(amidinobenzimidazoles) and bis(amidinoindoles) with varied linking chains connecting the aromatic groups and various modifications to the basic amidino groups have been prepared. The calf thymus (CT) DNA and nucleic acid homopolymer [poly(dA).poly(dT),poly(dA-dT).poly-(dA-dT), and poly(dG dC).poly(dG-dC)] binding properties of these compounds have been studied by thermal denaturation (delta Tm) and viscosity. The compounds show a greater affinity for poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) than for poly(dG dC).poly(dG-dC). Viscometric titrations indicate that the compounds do not bind by intercalation. Molecular modeling studies and the biophysical data suggest that the molecules bind to the minor groove of CT DNA and homopolymers. Analysis of the shape of the molecules is consistent with this mode of nucleic acid binding. Compounds with an even number of methylenes connecting the benzimidazole rings have a higher affinity for DNA than those with an odd number of methylenes. Molecular modeling calculations that determine the radius of curvature of four defined groups in the molecule show that the shape of the molecule, as a function of chain length, affects the strength of nucleic acid binding. Electronic effects from cationic substituents as well as hydrogen bonding from the imidazole nitrogens also contribute to the nucleic acid affinity. The bis(amidinoindoles) show no structurally associated differential in nucleic acid base pair specificity or affinity. PMID- 8510103 TI - Synthesis and tissue distribution of (m-[125I]iodobenzyl)trozamicol ([125I]MIBT): potential radioligand for mapping central cholinergic innervation. AB - Racemic (m-iodobenzyl)trozamicol (6, MIBT), a high-affinity vesamicol receptor ligand, was radiolabeled, resolved, and evaluated in rats. Following iv injection, (+)- and (-)-[125I]MIBT achieved initial brain levels of 0.57 and 0.92% dose/g of tissue, respectively. The level of (+)-[125I]MIBT subsequently declined by 74% within 3 h, while that of (-)-[125I]MIBT remained stable for the duration. Ex vivo autoradiographic mapping of (-)-[125I]MIBT distribution in rat brain revealed a pattern which was inconsistent with central cholinergic innervation. However, high levels of (+)-[125I]MIBT were observed over the amygdala, striatum, nucleus accumbens, olfactory tubercle, and nuclei of the fifth and seventh cranial nerves, while moderate to low levels were detected within the cortex, hippocampus, and cerebellum. Thus, the distribution of (+) [125I]MIBT parallels that of other presynaptic cholinergic markers. Co-injection of (+)-[125I]MIBT with 4-aminobenzovesamicol (2b), a potent vesamicol receptor ligand, reduced the levels of radiotracer in the striatum, cortex, and cerebellum by 58, 35, and 9%, respectively. Thus, (+)-[125I]MIBT binds to vesamicol receptors in vivo. In contrast, coadministration of (+)-[125I]MIBT with haloperidol (0.5 mumol/kg), reduced radiotracer levels in the cortex and cerebellum by 34 and 59%, respectively, while increasing the levels in the striatum by 32%. We conclude that although the distribution of (+)-[125I]MIBT qualitatively reflects cholinergic innervation, a fraction of radiotracer in the cortex and cerebellum is bound to sigma receptors. PMID- 8510104 TI - Characterization of a region of steric interference at the cannabinoid receptor using the active analog approach. AB - In this paper, it is hypothesized that the distinction between certain active and inactive cannabinoids is that the inactive analogs possess extra volume associated with their carbocyclic rings that may be responsible for an unfavorable interaction at the cannabinoid receptor. Using the active analog approach, a model is developed of a region of steric interference at this receptor using the active cannabinoids (-)-trans-delta 9-tetrahydrocannabinol, ( )-trans-delta 8-tetrahydrocannabinol, (-)-11-hydroxy-beta-hexahydrocannabinol, and a (-)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative and the inactive cannabinoids (9S,6aR)-trans-delta 10,10a-tetrahydrocannabinol and a (+)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative. Each of these molecules satisfy the cannabinoid pharmacophoric requirements, i.e., a phenolic oxygen at C1 and a side chain of acceptable length at C3. Accessible conformers of each molecule were identified by using the method of molecular mechanics as encoded in the MMP2(85) program. The MAP facility within the Chem-X molecular modeling program was then used to calculate the region of steric interference (termed the receptor essential volume, REV) from these accessible conformers. The calculations revealed an REV region located near the top of the carbocyclic ring in the bottom face of the molecule. In order to explore the use of this REV to account for the activities of other cannabinoids, the minimally active classical cannabinoid (-)-11-hydroxy-alpha hexahydrocannabinol, an active benzofuran cannabinoid, and the active nonclassical cannabinoid CP-47,497 were then studied. In each case, the activity or minimal activity of each compound can be explained on the basis of the ability of one or more accessible conformer of each molecule to clear the REV calculated here. The results of this study provide an explanation at the molecular level for observed activity differences between cannabinoids that exhibit shape differences associated with their carbocyclic rings. PMID- 8510105 TI - Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazoles. AB - A series of substituted 2-butylbenzimidazoles bearing a biphenylylmethyl moiety at the 1-position was prepared via three synthetic routes and evaluated for angiotensin II (AII) receptor antagonistic activity (in vitro and in vivo). Binding affinity was determined using bovine adrenal cortical membrane. Substitution at the 4-, 5-, or 6-position reduced the affinity relative to that of the unsubstituted compound (13a). However, most of the compounds with a substituent at the 7-position showed binding affinity comparable to that of DuP 753 (losartan). In functional studies, a carboxyl group was found to be very important for antagonistic activity against AII. Comparison of 2-butyl-1-[[2'-(1H tetrazol-5-yl)biphenyl-4-yl]methyl]- 1H-benzimidazole-4-, -5-, -6-, and -7 carboxylic acids (15a-d) in an AII-induced rabbit aortic ring contraction assay clearly demonstrated the importance of the substitutional position of the carboxyl group. In an in vivo assay, oral administration of benzimidazole-7 carboxylic acids caused long-lasting inhibition of the AII-induced pressor response in rats. The optimum substituent at the 7-position of the benzimidazole ring was found to be a carboxyl or an ester group. The representative compound, 2 butyl-1-[[2'- (1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxy lic acid (15d, CV-11194), inhibited the specific binding of [125I]AII to bovine adrenal cortical membrane with an IC50 value of 5.5 x 10(-7) M. The AII-induced contraction of rabbit aortic strips was antagonized by CV-11194 (IC50 value, 5.5 x 10(-11) M), while the compound had no effect on the contraction induced by norepinephrine or KCl. Orally administered CV-11194 at doses of 0.3-10 mg/kg dose dependently inhibited the AII-induced pressor response in rats and dogs. CV-11194 at 1 mg/kg po reduced blood pressure in spontaneously hypertensive rats (SHR). The three-dimensional molecular structure of CV-11194 was determined by X-ray diffraction. PMID- 8510106 TI - Nucleoside conjugates. 13. Synthesis and antitumor activity of 1-beta-D arabinofuranosylcytosine conjugates of thioether lipids with improved water solubility. AB - A series of ara-CDP-rac-1-S-alkyl-2-O-acyl-1-thioglycerols (3-12), analogues of highly active Cytoros2 (1), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. The conjugates with sn-1 alkyl (< C18) and sn-2 fatty acyl (< C14) substituents of the thioglycerol were water-soluble, while those with the sn-1 alkyl (> C14) and the sn-2 fatty acyl (> C16) were sparingly soluble. The latter formed micelles upon sonication. Conjugate 7 containing the sn-1 tetradecyl and the sn-2 palmitoyl (C16) groups formed micelles by both sonication and shaking. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 20 times greater than that of ara-C. The water-insoluble showed a more than 40 times increase. A single dose of the micelle-forming conjugates 7 and 10 produced a significant increase in life span (ILS > 421%) with 50% long-term survivors (> 45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of previous micelle-forming conjugate 1 (Cytoros). In contrast, the water-soluble conjugates at single doses were less effective (ILS 81-386% with 0-33% long-term survivors). However, three divided doses of the water-soluble conjugates were found to be as effective as a single dose of micellar solution of the water-insoluble. The results indicate that conjugate 7 and most of the water-soluble derivatives warrant further investigation. PMID- 8510107 TI - Synthesis, characterization, and anticancer activities of the first platinum complexes from sucrose. PMID- 8510108 TI - Laboratory evaluation of repellents against four anopheline mosquitoes (Diptera: Culicidae) and two phlebotomine sand flies (Diptera: Psychodidae). AB - Deet, the lactone CIC-4, and the piperidine compounds A13-37220 and A13-35765 were evaluated for initial repellency against laboratory-reared Anopheles albimanus Wiedemann, An. freeborni Aitken, An. gambiae Giles, An. stephensi Liston, and Phlebotomus papatasi (Scopoli) using a dose-response testing procedure on human volunteers. In addition, deet and CIC-4 were tested against Lutzomyia longipalpis (Lutz & Neiva). In general, the repellency of A13-37220, A13-35765, and CIC-4 was not markedly different from that of deet against each species tested; however, the different species varied greatly in response to the repellents. Overall, An. stephensi, L. longipalpis, and P. papatasi were the most sensitive, and An. albimanus the most tolerant species. The four repellents subsequently were tested against An. stephensi and An. albimanus to determine the duration of repellency. AI3-37220 provided effective (> 90%) protection against An. stephensi bites for 7 h, whereas deet, AI3-35765, and CIC-4 provided 6, 5, and 3 h of protection, respectively. Each of the four compounds provided < 1 h of protection against An. albimanus bites. PMID- 8510109 TI - Ixodid ticks (Acari: Ixodidae) and livestock production: effect of varying acaricide treatments on ticks and productivity in east coast fever-immunized weaner and dairy cattle. AB - In a pilot trial to evaluate cost-effective methods of acaricide application, east coast fever-immunized weaner and dairy cattle were subjected to varying tick control regimens. All experimental cattle were maintained under the same extensive system of management. Their monthly tick load, packed cell volumes, incidence of blood protozoans, weight changes, and daily milk production were noted. Apart from Rhipicephalus appendiculatus Neumann, other tick species found in the study site were R. pulchellus Gerstacker, Amblyomma gemma Donitz, Boophilus decoloratus Koch, and A. variegatum F. The control group under a weekly regimen of dipping had fewer ticks than each of the other groups for both weaner and dairy cattle. However, the percentage of increase in weight of the weaner cattle was least for the control group. The milk production of none of the groups was significantly different from that of the control group, although profit per animal for groups maintained under a monthly or six-weekly regimen of acaricide use was highest. The age of the experimental dairy cattle was found not to have any effect on their milk production. It is suggested that with successful immunization against east coast fever, both dairy and weaner cattle may be subjected to reduced dipping or spraying, the level of relaxation being dependent on the tick challenge. However, similar studies should be carried out in as many agroecological zones as possible using different breeds of cattle. Information on the level of acaricide residues in livestock products from different farming systems should also be generated. Only then can a definitive recommendation for a change from the present national intensive dipping policy be made. PMID- 8510110 TI - Gorging response of culicine mosquitoes (Diptera: Culicidae) to blood fractions. AB - Although anopheline mosquitoes will ingest plasma without blood cells, Culex spp. and Aedes spp. require the phagostimulatory effect of blood cells; this effect can be duplicated by the addition of adenine-nucleotides to plasma. Because activation of platelets released ADP and ATP into the plasma, they were suspected as the major source of the phagostimulant. This paper describes quantitatively the role of platelets in ingestion by Aedes aegypti (L.) and Culex univittatus Theobald. We found that about 10(6)/mm3 inactivated platelets are required to induce engorgement by 80-90% of the mosquitoes of both species. Thrombin activation of the platelets reduced the effective dose to < 2 x 10(4)/mm3. Other blood fractions also were tested as possible sources of stimulation. A series of washed red blood cells (RBC) dilutions was tested; 5 x 10(5) RBC/mm3 were required to induce 90% engorgement. Several types of leukocytes derived from blood by standard methods also induced engorgement at their physiological concentrations. Macrophages and cultured lymphocytes that do not contain any platelets induced gorging in Cx. univittatus, but not in Ae. aegypti. Because RBC and leukocytes do not release nucleotides unless broken, we suggest that their phagostimulatory effect is due to platelet contamination, which invariably occurs during standard methods of blood fractionation. PMID- 8510111 TI - Anopheles albimanus (Diptera: Culicidae) host selection patterns in three ecological areas of the coastal plains of Chiapas, southern Mexico. AB - The host-feeding patterns of Anopheles albimanus Wiedemann were described and the effect of host availability on these patterns was assessed in three different ecological areas of coastal Chiapas, Mexico. Resting mosquitoes were collected indoors and outdoors during rainy seasons. A 20% sample of blood-fed mosquitoes was tested to determine the source of the blood meal using an ELISA. The unweighted human blood index (HBI) of An. albimanus in the three areas ranged from 0.11 to 0.21. This mosquito species fed more frequently on bovines than on any other host, but the forage ratio indicated that there was also a high preference for equines. Some females tended to rest or complete their gonotrophic cycle indoors after feeding on animals, but females also fed on man and rested outdoors. Host availability and ecological conditions appeared to be responsible for differences observed in the HBI among areas. PMID- 8510112 TI - Vector competence of Aedes albopictus and Ae. aegypti (Diptera: Culicidae) to dengue 1 virus on Taiwan: development of the virus in orally and parenterally infected mosquitoes. AB - The vector competence in Ae. aegypti (L.) and Ae. albopictus (Skuse) from southern Taiwan to the dengue 1 virus was studied to elucidate the distribution of dengue infection during the 1987-1988 outbreak. The brain of Ae. aegypti was infected as early as 3 d after intrathoracic inoculation. The esophagus and the proboscis (tissues within the labium) were infected 5 d after inoculation. The salivary gland was highly susceptible to the virus, but no specific infection site was found. Gangli, muscles, and diverticula within the thorax were not infected. In the abdominal area, the ventral diverticula, Malpighian tubules, ganglia, and the dorsal vessel were not infected. However, the entire gut was susceptible to dengue 1 virus, although it was not infected simultaneously. Only a certain type of midgut epithelial cells was infected by the virus. The ovarioles, oviducts, and accessory glands frequently were infected. However, the spermathecae were not infected, perhaps because of the chitin-rich outer layer. Infections of the testes, vas deferens, seminal vesicles, and accessory glands of males also were detected in this study. The tissues of the proboscis were never infected in Ae. albopictus but frequently were infected in Ae. aegypti, indicating that the virus may escape the salivary gland barrier more efficiently in Ae. aegypti than in Ae. albopictus. When these mosquitoes were fed on hanging drops, the salivary gland infection and transmission rates of Ae. aegypti were always higher than those of Ae. albopictus. On Taiwan, Ae. aegypti appears to be a more competent vector in the transmission of the dengue 1 virus than Ae. albopictus. PMID- 8510113 TI - Population growth of Dermatophagoides farinae Hughes (Acari: Epidermoptidae) suppressed by methoprene and hydroprene. AB - Insect growth regulators are synthetic chemicals that mimic the function of hormones that occur naturally in arthropods. Two such insect growth regulators, methoprene and hydroprene, were tested to determine effects on growth of laboratory populations of the American house dust mite, Dermatophagoides farinae Hughes. Adults and immature mites were treated with four concentrations of each chemical in contact and diet-incorporation bioassays. Data were collected after 30 and 90 d of exposure to the treatments. Both compounds significantly suppressed population growth when compared with acetone controls at concentrations of > or = 5%. Methoprene was more effective than hydroprene in diet-incorporation bioassays and was slightly more effective for the first 30 d of the contact assays. A second set of contact and diet-incorporation assays was done using one concentration (7.5%) of methoprene and hydroprene to determine the effect of these compounds on population dynamics of D. farinae. In this experiment, population numbers were evaluated at weekly intervals for 13 wk. The average number of mites in the untreated control population increased by more than 10 times the original inoculum during the experiment while the number of mites in the treated containers did not increase significantly. This trend was similar for both contact and diet-incorporation bioassays although the average number of mites per container was significantly higher when the treatments were incorporated in the house dust mite diet than when applied directly to the substrate. PMID- 8510114 TI - Geographic variation of cuticular hydrocarbons among fourteen populations of Aedes albopictus (Diptera: Culicidae). AB - Cuticular hydrocarbons were used to differentiate among fourteen Aedes albopictus (Skuse) populations from Asia, Brazil, and the United States. Forty cuticular hydrocarbon peaks from each North American population were previously identified using gas chromatography electron impact-mass spectrometry. The same cuticular hydrocarbon peaks were identified in the Asian and Brazilian populations. Samples from three populations were analyzed using capillary gas chromatography chemical ionization mass spectrometry. Total carbon number and branch points were found for four peaks which occurred at equivalent chain lengths > 38.65. Quantitative analyses were performed by flame ionization gas chromatography. All populations contained the same cuticular hydrocarbons but showed differences in percentage composition. Nine of the 14 populations were separable by discriminant analysis of hydrocarbon components. Overlap of the 95% CIs occurred between the two Brazilian populations and among three North American populations. Individual specimens from three North American populations were used as a test group in the discriminant analysis. Correct classification of these individuals by population ranged from 80 to 100%. PMID- 8510116 TI - Computer-controlled olfactometer system for studying behavioral responses of ticks to carbon dioxide. AB - An olfactometer system that consisted of a laptop computer, a carbon dioxide analyzer, and an apparatus to control gas flows was designed to study ixodid tick behavioral responses to varying carbon dioxide (CO2) concentrations. The system provided a method to regulate and measure stimulatory CO2 concentrations (1-99 ppm) above ambient CO2 background levels. Adult Amblyomma americanum (L.) and Dermacentor variabilis (Say) demonstrated behavioral responses to CO2 concentrations as low as 9 ppm above the mean ambient background. Behavior (questing, initial movement, or activity rate) of adult ticks was observed before and during CO2 stimulation. Between the species, significantly more D. variabilis quested during stimulation, whereas significantly more A. americanum moved. Questing behavior between the sexes for either species was not significantly different. Initial movement for male A. americanum was significantly greater than for females. Activity rate was greater in A. americanum than in D. variabilis and significantly greater in male D. variabilis than in females. PMID- 8510115 TI - Temporal and spatial distribution of Ixodes pacificus and Dermacentor occidentalis (Acari: Ixodidae) and prevalence of Borrelia burgdorferi in Contra Costa County, California. AB - The seasonal activity and spatial distribution of adult and immature Ixodes pacificus Cooley & Kohls and Dermacentor occidentalis Marx were determined along trails and on hillsides in two parks in Contra Costa County, CA. I. pacificus and D. occidentalis adults were most numerous in January and May, respectively. Adult ticks were significantly more abundant along heavily vegetated trails than on open grassy hillsides, and on the uphill versus the downhill side of trails. Five species of rodents were captured, and numbers of I. pacificus and D. occidentalis larvae per rodent were highest in May-June and July, respectively. Few nymphs were recovered either by flagging or from captured rodents. An average of 2.2 and 2.8% of the I. pacificus adults collected from the two parks were infected with the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner. The greatest risk of contracting Lyme disease from adult I. pacificus in these two Contra Costa County parks is during the winter months, especially while hiking near the uphill side of trails. PMID- 8510117 TI - Ultrastructure of spotted fever rickettsialike microorganisms observed in tissues of Dermacentor taiwanensis (Acari: Ixodidae). AB - Tissues of midguts, Malpighian tubules, salivary glands, and ovaries of female Dermacentor taiwanensis Sugimoto collected in an area endemic for Japanese spotted fever were examined with an electron microscope, and the presence of two kinds of rickettsialike microorganisms was confirmed in Japan. Based on ultrastructural findings, a rod-shaped organism detected in all the tissues is a Rickettsia; another, irregularly shaped organism that was found only in the ovary, is a Wolbachia. A hemolymph test using a specific immunostain indicated that the Rickettsia belongs to the spotted fever group of rickettsiae. PMID- 8510118 TI - Adhesion to and invasion of cultured tick (Acarina: Ixodidae) cells by Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) and maintenance of infectivity. AB - Lyme disease spirochetes, Borrelia burgdorferi, interact with cultured tick cells in ways similar to those reported to occur in the vector Ixodes dammini Spielman, Clifford, Piesman & Corwin. Spirochete adhesion and penetration were examined using a cell line from embryos of Rhipicephalus appendiculatus Neumann that morphologically resembles tick gut cells, RAE25. Cocultivation of B. burgdorferi with these cells permitted prolonged maintenance of infectivity for hamsters. Borrelial adherence to RAE25 cells was time- and density-dependent and increased by 10-15% per h during the first 5.5 h of cocultivation when we used a concentration of 4 x 10(7) spirochetes/ml. After 6 h, > 90% of the cells bound an average of 3-5 spirochetes per cell. Low passage, hamster-infective strains of B. burgdorferi (JMNT and CD16) showed a 2-3-fold higher rate of adhesion to RAE25 cells than the highly passaged, noninfectious strain B31. Inactivation of CD16 or JMNT by heat, starvation, or treatment with puromycin reduced adherence by 40 60%, whereas pretreatment with monoclonal antibodies to the outer surface proteins had no effect. Spirochetes adhered to young I. dammini cell lines to a similar degree as they did to RAE25, whereas lines from the ticks Dermacentor variabilis (Say) (RML15) and Boophilus microplus (Canestrini) (BME26) bound 30 60% fewer spirochetes. Electron microscopy revealed epicellular borreliae associated with coated pits and vesicles before endocytosis, and intracellular spirochetes were surrounded by a host cell-derived membrane. PMID- 8510119 TI - Plasmodium vivax VK247 and VK210 circumsporozoite proteins in Anopheles mosquitoes from Andoas, Peru. AB - Anopheles mosquitoes captured in Andoas, Peru, a Plasmodium vivax-endemic area in the Peruvian Amazon region, contained both VK210 and VK247 P. vivax circumsporozoite (CS) proteins. Approximately 0.9% of the 4,403 mosquitoes tested by enzyme-linked immunosorbent assay were positive; 28% and 72% of the positive mosquitoes contained VK210 and VK247 CS proteins, respectively. These findings correlate strongly with a recent report of the presence of antibodies in residents of this area that recognize the VK210 and VK247 repeats, clearly indicating that both P. vivax CS protein polymorphs are common in the region. PMID- 8510120 TI - Distribution of container-inhabiting Aedes larvae (Diptera: Culicidae) at a dengue focus in Thailand. AB - A Thai village with dengue transmission was surveyed for Aedes aegypti (L.) and Ae. albopictus (Skuse) larvae at the end of the rainy season. All containers (1,819) in 186 households were surveyed, recording the presence of larvae, container type, level of water, kind of cover, and location. The number of positive containers was proportional to the total number of containers in a household. Standard water jars (approximately 200 liters) contributed 57% and small water jars (< 100 liters) contributed 16% of the total infested containers. Each of the other 10 container types contributed < or = 10% of the total infested containers and were not statistically different from each other. Containers inside houses were infested significantly more often than were those outdoors, those under elevated houses or roofs, or those in bathrooms. Unexpectedly, standard water jars located outdoors that were covered with commercial metal lids were infested significantly more often than were uncovered jars. PMID- 8510121 TI - Competence of Peromyscus maniculatus (Rodentia: Cricetidae) as a reservoir host for Borrelia burgdorferi (Spirochaetares: Spirochaetaceae) in the wild. AB - Although capable of maintaining and transmitting Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner, the causative spirochete of Lyme disease, in the laboratory, the specific ability of deer mice, Peromyscus maniculatus Le Conte, to support this zoonosis has not been established. Demonstration that P. maniculatus is a competent reservoir host in the wild would indicate that the spread of Lyme disease is not limited to the range of the primary reservoir host, P. leucopus Rafinesque. Isle au Haut, an offshore Maine island upon which the vector tick Ixodes dammini Spielman, Clifford, Piesman & Corwin has become established, supports an isolated population of mice that are exclusively P. maniculatus. We examined the reservoir competence of this species by comparing infection rates of B. burgdorferi among juvenile ticks removed from livetrapped mice on this island with those removed from P. leucopus obtained at a mainland site endemic for Lyme disease. Equivalent rates of infection among engorged larval ticks, survival of infection through the larval-nymphal molt, and the isolation of B. burgdorferi from mice at both sites attest to the reservoir competence of P. maniculatus. PMID- 8510122 TI - Efficacy of diflubenzuron in simulated household and yard conditions against the cat flea Ctenocephalides felis (Bouche) (Siphonoptera: Pulicidae). AB - Diflubenzuron-treated carpet inhibited egg-to-adult development of the cat flea for up to 12 mo even with weekly vacuuming of the carpet. The efficacy of diflubenzuron was similar in treated soils over a 6-mo test period except in the case of treated soil that remained outside. Reduced efficacy is attributed to degradation of diflubenzuron by microorganisms and water. PMID- 8510123 TI - Baseline entomological data for a pilot malaria control program in Equatorial Guinea. AB - Entomological studies conducted on the island of Bioko and the mainland province, Rio Muni, in Equatorial Guinea provided baseline data for a pilot malaria control program. The main species collected resting in houses at low density were Anopheles gambiae s.l. Giles and Anopheles funestus Giles. An. gambiae s.l. density increased during the rainy season, whereas An. funestus populations remained stable during both dry and wet seasons. Both species tended to be endophilic and were not collected resting or biting outdoors. Overall, delayed sporozoite rates were about 10% for both species and were highest in the dry season. An. gambiae s.l. from the mainland showed resistance to 4% DDT, but the island population was still susceptible. All populations were completely susceptible to 5% malathion and 0.025% deltamethrin. PMID- 8510124 TI - Culicoides (Diptera: Ceratopogonidae) associated with white-tailed deer habitat and livestock operations in the northern Great Plains. AB - Twelve Culicoides species were collected from white-tailed deer habitat and cattle operations in the Northern Great Plains as part of an ongoing study of the geographical distribution and seasonal occurrence of C. variipennis and other species in North Dakota. C. variipennis, C. obsoletus, and C. stellifer were collected in both western and eastern counties. C. arboricola, C. hinmani, C. nanus, and C. palmerae are reported for the first time from North Dakota. PMID- 8510125 TI - Scanning electron microscopy of the egg of Culex tritaeniorhynchus (Diptera: Culicidae). PMID- 8510126 TI - Isolation of Leishmania mexicana (Kinetoplastida: Trypanosomatidae) from Lutzomyia anthophora (Diptera: Psychodidae) collected in Texas. AB - Three of 27 female Lutzomyia anthophora (Addis) collected in Texas from the nest of a southern plains woodrat, Neotoma micropus Baird, during October 1991 were infected with flagellate protozoans. Isolates were grown in Schneider's Drosophila medium supplemented with 20% fetal bovine serum, and isozyme analysis of two of the isolates determined the parasites to be Leishmania mexicana (Biagi). These are the first isolations of Leishmania from field-collected sand flies in North America north of Mexico. Possible reasons for the lack of human cases near the focus are presented. PMID- 8510127 TI - An unexpected result from burning vegetation to reduce Lyme disease transmission risks. AB - The risk for human infection with Lyme disease appears linked to the abundance of infected vector ticks, principally Ixodes dammini Spielman, Clifford, Piesman & Corwin, in the eastern United States. Habitat destruction by burning, although not well studied, has long been considered as an effective alternative to synthetic insecticides as a means of reducing tick populations. We evaluated the effect of a single spring burning of the woodland understory on the transmission risk of Lyme disease spirochetes (Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner) on Shelter Island, Long Island, NY. Following a burn in early April 1991, the abundance of nymphal I. dammini was 49% lower in the burned portion of a woodlot compared with the unburned portion. However, risk of encountering nymphs infected with B. burgdorferi remained similar in both burned and unburned woods. It is suggested that burning vegetation may disproportionately kill deer-derived rather than rodent-derived nymphs, significantly reducing tick abundance without affecting transmission risk. PMID- 8510128 TI - Chrysomya albiceps and C. rufifacies (Diptera: Calliphoridae): contribution to an ongoing taxonomic problem. AB - Until recently, the two biologically equivalent blow flies Chrysomya albiceps (Wiedemann) and Chrysomya rufifacies (Macquart) had disjunct distributions outside the Americas; the former was Palaearctic, the latter Australasian and Oriental. The two species are now spreading throughout the Americas and coexist in Argentina. The predatory "hairy" larvae of both species are difficult to separate, which could result in taxonomic errors. New diagnostic characters are presented to differentiate the third instars of the two species. The usefulness of the prostigmatic bristle as a diagnostic taxonomic character in distinguishing adults of these species is questioned. PMID- 8510129 TI - Iron and infection: better understanding at the molecular level but little progress on the clinical front. PMID- 8510130 TI - Co-agglutination (Co-A) test for circulating antigen in hydatid disease. AB - A co-agglutination (Co-A) test with Staphylococcus aureus (Cowan's strain I) bearing protein A coated with specific hydatid antibodies, was used to demonstrate circulating hydatid antigen in serum for the diagnosis of hydatid disease. The test had a sensitivity of 95% and specificity of 89% in detecting hydatid antigen in serum. A false positive reaction was observed with 18.5% of control sera from patients with various parasitic diseases. However, these all gave negative results when tested after further dilution. The test is reliable and rapid; the result could be obtained within 30-45 min of receipt of a serum sample. Since the test is simple and the reagents are inexpensive and easily available, it can be used in less well equipped laboratories in developing countries. PMID- 8510131 TI - Induction of inflammatory cytokines by a soluble moiety prepared from an enzyme lysate of Actinomyces viscosus cell walls. AB - A carbohydrate-rich and immunobiologically active component, M1Av, was prepared from an M-1 endo-N-acetylmuramidase digest of cell walls of Actinomyces viscosus ATCC 19246 by CM Sephadex C-25 and Sephadex G-100 chromatography. M1Av stimulated thioglycolate-induced peritoneal macrophages from C3H/HeN and C3H/HeJ mice to release cell-free tumour necrosis factor (TNF) and interleukin (IL)-6, and a cell associated thymocyte activating factor, probably IL-1. An intravenous (i.v.) injection of M1Av induced increased levels of TNF and IL-6 in the serum of C3H/HeN mice that had been primed with 100 micrograms of muramyldipeptide (MDP) i.v. However, M1Av did not induce TNF release in C3H/HeJ mice similarly primed with MDP. Simultaneous administration of M1Av (100 micrograms, i.v.) and galactosamine (18 mg, intraperitoneally) killed C3H/HeN, but not C3H/HeJ mice. M1Av was shown to be practically free of endotoxin by the Limulus test. These findings indicate that the solubilised A. viscosus cell-wall carbohydrate moiety induced inflammatory cytokines both in vitro and in vivo. PMID- 8510132 TI - Sensitisation of cariogenic bacteria to killing by light from a helium-neon laser. AB - Suspensions of the cariogenic bacteria Streptococcus mutans, S. sobrinus, Lactobacillus casei and Actinomyces viscosus were exposed to light from a 7.3-mW helium-neon laser in the presence of toluidine blue O. A substantial killing rate (c. 10(6) cfu) of all four species was achieved with a dye concentration of 50 micrograms/ml and a light energy dose of 33.6 J/cm2. This was achieved in 60 s, an exposure time that is clinically acceptable. Exposure to laser light in the absence of the dye did not significantly affect the viability of any of the organisms. This approach may be useful in dentistry to sterilise a carious lesion prior to its repair. PMID- 8510133 TI - Confocal laser scanning microscopy of peritoneal catheter surfaces. AB - Surface topography of used (in situ > 12 months) and unused CAPD catheters was studied by scanning electronmicroscopy (SEM) and confocal laser scanning microscopy (CLSM). Microbial biofilm was observed on all used catheters. Disruption and removal of the attached biofilm revealed extensive pitting of the catheter surface and scoring within the catheter pores. Similar, though less extensive, surface defects were present in unused catheters. Examination by CLSM, with software specific to the determination of surface topography, showed used catheters to have a surface microrugosity greater than that of unused catheters (p < 0.0005). Adherence studies with radiolabelled Staphylococcus epidermidis demonstrated increased adherence to used than to unused catheters (p < 0.0005) after 48 h. However, when catheters were pre-treated with spent dialysate there was a substantial reduction in bacterial adherence to either catheter and no significant difference in adherence to used and unused catheters. Surface microrugosity of CAPD catheters increases during use but is unlikely to be an important factor in bacterial adherence in vivo. PMID- 8510134 TI - The morphology of Chlamydia pneumoniae. AB - The morphology of a recently isolated strain of Chlamydia pneumoniae, YK-41, was compared by electronmicroscopy with C. pneumoniae TWAR, Chlamydia trachomatis L2/434/Bu and Chlamydia psittaci Cal 10. The results showed that "pear-shaped" morphology was not typical of C. pneumoniae. Basic morphological features, such as surface projections and hexagonally arrayed, regular structures in the inside layer of the outer membrane of elementary bodies, were very similar in these strains. The structure of strain YK-41 was identical with that of C. trachomatis and C. psittaci, but the profiles of elementary bodies were different from those of C. pneumoniae TWAR strains. PMID- 8510135 TI - Comparison of different primer sets for detection of Chlamydia trachomatis by the polymerase chain reaction. AB - The sensitivity and specificity of the polymerase chain reaction (PCR) method was studied in vitro with HeLa cells infected with Chlamydia trachomatis serovar L2. Three different primer sets were studied; they were derived from the endogenous plasmid, the nonvariable part of the MOMP gene and the 16S ribosomal RNA (rRNA) gene. The plasmid primers were the most sensitive in the PCR method and detected at least 0.1 infectious unit of C. trachomatis in the presence of a superfluous amount of human DNA. Application of this plasmid PCR to 13 C. trachomatis culture positive cervical smears containing < 10- > 200 inclusion-forming units showed that it was the most sensitive of the three methods and detected C. trachomatis in all samples. This correlates with the observation that the plasmid PCR method could detect C. trachomatis in cervical smears of four symptomatic patients for up to 3 weeks after the start of treatment with doxycycline. In contrast, the MOMP gene- and rRNA gene-directed PCR, as well as culture and direct immunofluorescence, gave negative results within 1 week. Therefore, we conclude that the plasmid primers are the best candidates for use in the PCR method in C. trachomatis screening programmes and clinical follow-up studies. PMID- 8510136 TI - Serogroup F strains of Clostridium difficile produce toxin B but not toxin A. AB - Most toxigenic strains of Clostridium difficile produce two toxins: an enterotoxin (toxin A) and a cytotoxin (toxin B). Only one strain (strain 8864) has been reported to produce toxin B but no toxin A. Serogroup F strains (44) of C. difficile, often isolated from asymptomatic infants, have been examined for toxin production. These strains, which were from distinct geographical and clinical sources, did not produce any detectable toxin A in vitro when examined in three distinct immunoassays. Nevertheless, all the strain produced a cytotoxin. Immunological differences between the cytotoxin of the serogroup F strains and that produced by C. difficile strain VPI 10463 (serogroup G) were demonstrated with monoclonal antibodies specific for either the toxin B produced by C. difficile strain VPI 10463 or C. sordellii lethal toxin (LT). Polymerase chain reaction amplification with primers derived from C. difficile strain VPI 10463 toxin A and B genes showed that serogroup F strains seem to possess a toxin B gene homologous with that of strain VPI 10463 and at least fragments of the toxin A gene. When axenic mice were inoculated with serogroup F strains, the animals survived; they did not develop diarrhoea and no toxin A could be detected in their faeces. However, cytotoxin was detected. Furthermore, these mice were protected against subsequent challenge with the otherwise lethally toxigenic C. difficile strain VPI 10463. The serogroup F strains appeared to be homogeneous and distinct from other C. difficile strains with regard to toxin production. PMID- 8510137 TI - Alteration of transfer ribonucleic acid of Neisseria meningitidis during growth in the presence of human transferrin. AB - Iron-related tRNA alterations have been shown to occur in several pathogens but nothing has been reported about the effect of iron on meningococcal tRNA. The chromatographic elution profile of 3H-tryptophan-tRNA(trp) from a Neisseria meningitidis strain grown under different conditions was examined. The profile showed an early (P1) and a late (P2) eluting species of tRNA(trp), but the proportion of the two species varied under different growth conditions. The elution profile of trp-tRNA(trp) from bacteria grown in iron-sufficient Mueller Hinton broth yielded a minor P1 species and a major P2 species, whereas under iron-restricted growth induced by desferrioxamine, the pattern was one of a major P1 species and minor P2 species. Iron-restriction induced by human transferrin (HTF) resulted in almost equal amounts of the two tRNA(trp) species (P1 congruent to P2). Differences in the proportions of the tRNA species were also found between cells grown in liquid medium (P1 << P2) and on the same medium solidified with agar (P1 >> P2). The growth phase of the bacteria did not have any effect on the tRNA(trp) elution profile. Changes in tRNA(trp) induced by HTF were readily and completely reversible when the cells were transferred to an iron-rich medium, but those induced by desferrioxamine remained irreversible for a long period (16 h) after such transfer. PMID- 8510138 TI - Diagnosis of Pneumocystis carinii pneumonia: specificity and sensitivity of polymerase chain reaction in comparison with immunofluorescence in bronchoalveolar lavage specimens. AB - DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP. PMID- 8510139 TI - The effects of RU 41.740, a glycoprotein immunomodulating agent derived from Klebsiella pneumoniae, on intra-abdominal abscess formation in mice. AB - The prophylactic and therapeutic efficacies of the immunomodulating agent RU 41.740 (a glycoprotein extract from Klebsiella pneumoniae) were studied in a murine model of intra-abdominal abscess formation with Bacteroides fragilis, Escherichia coli, and bran as an abscess-potentiating agent. Parenteral injection of RU 41.740, either before or after injection of an abscess-inducing mixture (AIM), was associated with significantly diminished incidence and size of abscesses. Abscess incidence and size were significantly decreased by oral administration of RU 41.740 after, but not before, AIM injection. Abscess formation and resolution are the results of complex interactions of host defence mechanisms with bacteria and potentiating agent, and RU 41.740 has been shown previously to activate both macrophage and neutrophil function. These results indicate that activation of non-specific defences may protect against abscess development in chronic sepsis. PMID- 8510140 TI - Missense mutations in the Bacillus subtilis gnt repressor that diminish operator binding ability. AB - The Bacillus subtilis gnt operon is negatively regulated by the gnt repressor (GntR, 243 amino acids), which is antagonized by gluconate. The GntR protein belongs to a new family of bacterial regulatory proteins (GntR family). To locate the DNA-binding domain of the GntR protein, we obtained mutations of this protein, by hydroxylamine mutagenesis, which diminish its operator binding ability. Sequence analysis of these mutations indicated that the mutant GntR proteins (GntR43L, GntR66T, GntR74K and GntR75Q) had amino acid substitutions (Ser43 to Leu, Ala66 to Thr, Glu74 to Lys and Arg75 to Gln), respectively. They were all located within the N-terminal conserved region of the GntR family. In vivo and in vitro analysis of these GntR proteins indicated that their relative operator binding abilities became weaker in the order of GntR (wild type), GntR66T, GntR75Q, GntR74K and GntR43L. The equilibrium dissociation constants of GntR (wild type), GntR66T, GntR75Q and GntR74K as to operator binding were determined by gel retardation assays to be 0.43, 2.6, 4.2 and 8.8 M x 10(-10), respectively. PMID- 8510141 TI - Template-directed and template-free RNA synthesis by Q beta replicase. AB - In the absence of extraneously added templates, Q beta replicase produces different RNA species after long lag times spontaneously in vitro. The sequences of the spontaneous products are short (30 to 45 nucleotides) and bear little sequence relation to one another and no detectable sequence homology to Q beta virus RNA or to the host. Their replication rates are much lower than those of optimized products. Incubation without template in long closed capillaries produces after long lag times many separate RNA growth foci with heterogeneous kinetics. The template-free reaction is strongly dependent on the conditions: lowering the enzyme or the triphosphate concentrations abolishes the template free RNA synthesis without affecting the template-dependent synthesis. An explanation of the emerging RNA species in template-free reactions by residual RNA contaminants in the incubation mixture is very unlikely in the light of the experimental evidence; however, the experimental evidence is fully compatible with a de novo mechanism (which may include instruction by non-replicatable oligonucleotides). PMID- 8510142 TI - Structural differences between wild-type NADP-dependent glutathione reductase from Escherichia coli and a redesigned NAD-dependent mutant. AB - NAD and NADP are ubiquitous coenzymes in biological redox reactions. They have distinct metabolic functions, yet they differ only by an additional phosphate group esterified at the 2'-hydroxyl group of the AMP moiety of NADP. The natural specificity of Escherichia coli glutathione reductase for NADP has previously been converted into a marked preference for NAD by introducing seven point mutations into the beta alpha beta-fold of the NADP-binding domain of the protein based on the known structure of the human enzyme. Among them was the replacement of Ala179 by glycine (A179G) in the alpha-helix of the fold, a change suggested by a difference in a sequence fingerprint previously found in the dinucleotide binding domains of a number of dehydrogenases. Although this position is at a distance of 10 A from the bound 2'-phosphate group of NADP in glutathione reductase, the A179G mutation was found to be synergistic and beneficial. We have now carried out X-ray crystallographic analyses of the NAD-dependent mutant without and with bound NADH. A comparison of the structures of the mutant and wild-type enzymes reveals a flip of the peptide bond between Gly174 and Ala175 such that the side-chain of another introduced amino acid, Glu197, is fixed and can participate in binding the adenine ribose of NAD, thereby contributing to the ability of the mutated enzyme to exert its selectivity for the "wrong" coenzyme. PMID- 8510143 TI - La proteins from Xenopus laevis. cDNA cloning and developmental expression. AB - In mammalian nuclei, newly-synthesized RNA polymerase III transcripts are transiently associated with a phosphorylated polypeptide of approximately 50 kDa called the La protein. Here we provide evidence that the frog Xenopus laevis contains mRNAs for two highly related La proteins, each apparently encoded by a single gene. Both forms of the La protein contain the RNP-80 motif previously identified in many RNA binding proteins. The steady state levels of La mRNAs and protein are approximately constant in oocytes, eggs and embryos. This implies a progressive and severe decrease in these levels on a per cell basis during early development. In particular, neither the La mRNA nor protein level increases at the mid-blastula transition, the time when RNA polymerase III transcription first occurs during embryogenesis. PMID- 8510144 TI - AraC protein can activate transcription from only one position and when pointed in only one direction. AB - At the araBAD promoter, the RNA polymerase-proximal half-site for AraC binding partially overlaps the -35 region. Random and explicit spacing experiments show that both this partial overlapping and AraC binding to the polymerase-proximal half-site are necessary and sufficient for strong transcriptional activation. Normally, this occupancy is generated by the presence of arabinose, which shifts AraC from a DNA looping interaction involving the polymerase-distal half-site and the araO2 site 210 base-pairs away, to an interaction with the two half-sites adjacent to RNA polymerase. Changing the polymerase-proximal half-site to a higher affinity AraC binding site gives activation in the absence of arabinose. Thus, arabinose is not required to transform AraC into an activating conformation. Because the two half-sites of araI are direct repeats, the RNA polymerase proximal and distal surfaces of AraC are not identical. When the araI site was turned around, no spacings were found from which AraC could activate transcription. In light of the strict spacing and orientation requirements for AraC activation, the interactions between AraC and RNA polymerase are likely to be specific and inflexible. PMID- 8510145 TI - Recognition nucleotides of Escherichia coli tRNA(Leu) and its elements facilitating discrimination from tRNASer and tRNA(Tyr). AB - In order to study how Escherichia coli leucyl-tRNA synthetase recognizes tRNA(Leu) and discriminates it from the other two class II tRNAs, tRNA(Ser) and tRNA(Tyr), various mutations were introduced into class II tRNA transcripts. The discriminator base A73, but not the anticodon sequence, was found to serve as a critical recognition element of tRNA(Leu). A base substitution at the invariant nucleotide A14, but not at any of the other nucleotides characteristic of the E. coli tRNA(Leu) isoacceptors among the three class II tRNAs, caused significantly damaged aminoacylation with leucine. A two base-pair deletion in the long variable arm also resulted in no significant decrease of activity. Transplanting the three tertiary elements characteristic of E. coli tRNA(Leu) (i.e. the location of the G18G19 sequence in the D-loop, the A15 U48 base-pair and the stem pairing pattern of the long variable arm) besides the discriminator base change introduced the leucine charging activity in terms of Vmax/Km, up to 0.1 of that for the normal sequence of tRNA(Leu) into both tRNA(Ser) and tRNA(Tyr). These results indicate that A73 and A14 (or its vicinity) are involved in recognition by leucyl-tRNA synthetase, and that several tertiary elements play a significant role in the discrimination of tRNA(Leu) from the other two class II tRNAs. PMID- 8510146 TI - Electron microscopy of DNA excision repair patches produced by human cell extracts. AB - To characterize the process by which the mammalian nucleotide excision repair complex interacts with DNA to recognize and repair lesions, we have investigated the size and distribution of repair patches induced by human cell extracts in ultraviolet light-irradiated plasmid DNA. Repair synthesis was carried out in a buffer substituting biotinylated dUTP for dTTP, to allow repair patches to be detected by electron microscopy after streptavidin/colloidal gold labelling. Individual repair events on circular plasmids that had undergone repair synthesis in cell extracts were scored as gold particles bound specifically to irradiated molecules. Samples of over 2000 irradiated and unirradiated plasmids were counted. Repair synthesis at ultraviolet light photoproducts typically replaced about 30 nucleotides, since 69% of patches contained only one particle of 10 nm gold and 24% of patches contained two gold particles (each covering approx. 29 nucleotides). In addition, the ordering of repair events among damaged plasmids closely fitted a Poisson distribution, indicating that repair of lesions is achieved via a non-processive, random diffusion mechanism. This suggests that the repair complex is not intrinsically processive. PMID- 8510147 TI - Solution structure of selenocysteine-inserting tRNA(Sec) from Escherichia coli. Comparison with canonical tRNA(Ser). AB - Selenocysteine-inserting tRNAs (or tRNA(Sec)) are structurally untypical tRNAs that are charged by seryl-tRNA synthetase before being recognized by the selenocysteine synthase that converts serine into selenocysteine. tRNA(Sec) from Escherichia coli contains 95 nucleotides and is the longest tRNA known to date, in contrast to canonical tRNA(Ser), 88 nucleotides-long. We have studied its solution conformation by chemical and enzymatic probing. Global structural features were obtained by cobra venom and S1 nuclease mapping, as well as by probing with Pb2+. Accessibilities of phosphate groups were measured by ethylnitrosourea probing. Information about positions in bases involved in Watson Crick pairing, in stacking or in tertiary interactions were obtained by chemical probing with dimethylsulfate, diethylpyrocarbonate, kethoxal and carbodiimide. On the basis of these chemical data, a three-dimensional model was constructed by computer modeling and compared to that of canonical tRNA(Ser). tRNA(Sec) resembles tRNA(Ser) at the level of its T-arm and anticodon-arm conformations, as well as at the joining of the D- and T-loops by a tertiary Watson-Crick G19-C56 interaction. Its extra-long variable arm is a double-stranded structure closed by a four nucleotide loop that is linked to the body of the tRNA in a way different from that found in tRNA(Ser). As anticipated from the peculiar features of the sequence in the D-loop and at the junction of amino acid and D-arms, tRNA(Sec) possesses a novel but restricted set of tertiary interactions in the core of its three-dimensional structure: a G8-A21-U14 triple pair and a novel interaction between C16 of the D-loop and C59 of the T-loop. A third triple interaction involving C15-G20a-G48 is suggested but some experimental evidence for it is still lacking. It is furthermore concluded that the D-arm has six base-pairs instead of three, as in canonical class II tRNA(Ser), with the D-loop containing only four nucleotides. Finally, the amino acid accepting arm forms a stack of eight Watson-Crick base-pairs (instead of 7 in other tRNAs). The biological relevance of this model with regard to interaction with seryl-tRNA synthetase and enzymes from the selenocysteine metabolism is discussed. PMID- 8510148 TI - Distortion of the DNA double helix by RAP1 at silencers and multiple telomeric binding sites. AB - Repressor Activator Protein 1 (RAP1) is an essential nuclear protein of the yeast Saccharomyces cerevisiae that recognizes a 13 base-pair (bp) consensus sequence found in numerous upstream activating sequences, at the silencers of transcriptionally repressed mating-type genes, and in telomeric tracts, called (C1-3 A) repeats. RAP1 has been shown to influence transcriptional activation, transcriptional repression, telomere length, circular plasmid segregation and meiotic recombination in vivo. We have studied the structure of the protein-DNA complex reconstituted in vitro with highly purified RAP1, by using DNase I and chemical footprinting. Both full-length RAP1 and its minimal DNA-binding domain of roughly 30 kDa, induce a distortion within the 13 bp recognition site, as demonstrated by reactivity to KMnO4 primarily at nucleotides 8 and 10 in the binding consensus Rc/AAYCCRYNCAYY. Dimethylsulphate reactivity shows that RAP1 binding does not create unpaired regions at its binding site, although the DNA may be locally underwound or aberrantly base-paired at the permanganate reactive nucleotides. In addition to the permanganate-sensitive distortion, the full length RAP1, but not its DNA-binding domain, induces a bend in DNA 5' of the recognition sequence, altering the electrophoretic mobility of the protein-DNA complex. The KMnO4-reactivity has allowed a precise mapping of RAP1 molecules on telomeric DNA, revealing RAP1 sites as frequently as one per 18 bp of telomeric DNA, or potentially 20 RAP1 molecules bound per average telomeric tract of 370 bp. This suggests that RAP1 plays a major role in organizing yeast telomeres, and is consistent with recently published immunofluorescence studies showing a major fraction of RAP1 at the ends of meiotic chromosomes. PMID- 8510149 TI - Ionic interactions in the coiled-coil domain of laminin determine the specificity of chain assembly. AB - Laminins are a family of large (800 to 900 kDa) multidomain glycoproteins specifically found in basement membranes. They consist of one heavy A chain and two light chains B1 and B2, and several tissue-specific laminin isoforms exist. Chain assembly is mediated through the formation of a rod-like triple-stranded alpha-helical coiled-coil domain about 75 nm long. The interacting edges of the chains are mostly formed by hydrophobic residues in positions a and d of an (abcdefg)n heptad sequence repeat and by a distinct pattern of charged residues in positions e and g. Here, we have analyzed the sequences of known laminin chains in an effort to relate them to interaction potential. Initially, those sequences localized in the long arm were arranged in an optimum heptad-repeating scheme. The interacting edges between chains were then analyzed for interchain hydrophobic and ionic interactions. The short heptad blocks were allowed to shift axially with respect to each other to maximize the number of interactions. The number of hydrophobic interactions was very high and similar for all chain combinations, but especially so for homodimers. As these were not observed experimentally, it seems that hydrophobic interactions probably represent only a prerequisite for coiled-coil formation. The number of ionic interactions, however, directly resembles the interaction potential observed in in vitro experiments. In particular, the number of interchain ionic interactions is high for parallel heterodimer configurations of A and B chains, but low for homodimer arrangements. When the laminin isoform chains, rat s-laminin (B1s) and human merosin (Am), are included in the analysis, they show rather low numbers of mutual interactions but high ionic interaction potentials between them and distinct mouse laminin chains are predicted. For mouse laminin the analysis was extended to a full three-stranded coiled-coil structure. The highest number of interchain ionic interactions occurs for an anti-clockwise chain arrangement of A ->B1-->B2 when viewed from the N terminus. None of the laminin chains appears to be designed for the formation of homodimers, although such conformations are frequently found in other alpha-fibrous proteins. PMID- 8510150 TI - Two secretory protein genes in Chironomus tentans have arisen by gene duplication and exhibit different developmental expression patterns. AB - The salivary gland cells in the dipteran Chironomus tentans produce approximately 15 different secretory proteins, with relative molecular masses ranging between 1 x 10(4) and 1 x 10(6). Together these proteins form two types of extra corporal tubes, a larval protective housing and feeding tube or a pupation tube. The developmental change in tube formation is accompanied by a switch in production from one combination of secretory proteins to another. Here we characterize two genes, the sp38-40.A and B genes, which encode secretory proteins with relative molecular masses of 38,000 to 40,000. The two genes are located 346 base-pairs apart in the same orientation and have presumably arisen by gene duplication as the result of an illegitimate recombination event. Both genes contain two regions with cysteine codons, surrounded by regions with short repeats coding for proline and charged amino acid residues. The two genes and alleles of the genes differ in their number of repeats. This structure resembles the structure of the Balbiani ring (BR) genes, which encode the four largest salivary gland secretory proteins. The sp38-40.A and B genes are therefore likely to belong to a BR multigene family containing all or most of the 15 salivary gland secretory protein genes. The expression of the sp38-40.A and B genes are different: the A gene is expressed throughout the larval fourth instar but considerably less in the prepupal stage, while the B gene shows the opposite expression pattern. The developmental regulation of the expression of the two genes has therefore diverged after the gene duplication event. PMID- 8510151 TI - Clustered arginine residues of bacteriophage lambda N protein are essential to antitermination of transcription, but their locale cannot compensate for boxB loop defects. AB - The N protein coded by bacteriophage lambda plays an essential role in the completion of lambda transcription by recognizing the boxB sequence in nascent transcripts and then aggregating with Escherichia coli RNA polymerase and four other E. coli proteins into an unstoppable transcription complex. In order to explore the functionality of N protein and the specific recognition between N and boxB, 14 amino acid positions near the amino-terminal end of N lambda were mutated extensively. The mutant proteins were scored for N function in vivo by a two-plasmid construct that visualizes readthrough transcription as lacZ expression in colonies of E. coli. Mutation was achieved by single TAG replacements, translated through suppression into 13 different amino acids, or by scrambling at assorted three-codon sets. Of the 14 amino acid positions tested (Tables 5 and 6), six remained functional with a wide variety of substitutions, while substitution was sometimes deleterious at one Ala and two Gln positions. At each of the five Arg positions, however, maintenance of Arg occupancy proved important for N function. Despite effective screening for increased N function at boxBs with defective loops, no N mutant, simple or complex, was found to change the order of preference of wild-type N lambda for boxBs with defective loops. Thus, although multiple amino-terminal Arg positions are found to be important for N function, mutations in the region spanning the five Arg residues were not found to compensate for defects in boxB loop. PMID- 8510152 TI - Studies of bacteriophage P2 DNA replication. The DNA sequence of the cis-acting gene A and ori region and construction of a P2 mini-chromosome. AB - A self-replicating plasmid was constructed from the 76.7 to 91.6% region of bacteriophage P2, which contains the P2 origin or replication (ori) and the genetically defined replication genes B and A. The sequence of the 76.7 to 80.2% has been determined previously, and the sequence of the 80.2 to 91.6% region is now reported. The sequenced region contained gene A, which predicts a 761 amino acid residue polypeptide known to induce a single-strand cut at or near ori, and ori, which has been located by electron microscopy to about 89% from the left end of the phage genome. Analysis of plasmid-encoded proteins in minicells indicated that the A gene product was about 78 kilodaltons. Five previously unknown open reading frames (orf-80, orf-81, orf-82, orf-83 and orf-91) were discovered. They have been cloned and their respective products were identified. The products of orf-80, orf-82 and gene A were found to be lethal to the host when overexpressed. The predicted amino acid sequences of the orf-82 and orf-83 gene products were similar to two early gene products of phage 186; the orf-91 product resembled the hypothetical protein of orfd of retron Ec67. Similarities between the products of P2 gene A, 186 gene A and orf2 and orf3 of Ec67 were also found. A P2 mini chromosome has been constructed that contains only the P2 A gene and the beta lactamase gene as a marker. PMID- 8510153 TI - Three-dimensional structure of satellite tobacco mosaic virus at 2.9 A resolution. AB - The crystal structure of satellite tobacco mosaic virus (STMV) has been solved by a combination of multiple isomorphous replacement and molecular replacement methods and refined at 2.9 A resolution to a conventional R-factor of 0.215. STMV, a T = 1 icosahedral virus, is the smallest whose structure has been determined. The coat protein is an eight-stranded "Swiss roll" beta-barrel with an amino-terminal strand that extends away from the beta-barrel by more than 60 A. This strand is primarily responsible for quaternary interactions within the capsid. The most arresting feature of the virus structure is the intimate association of each capsid protein dimer with a Watson-Crick base-paired segment of RNA double helix on the interior of the virion. The icosahedral 2-fold axis of each dimer pair is coincident with that of the central base-pair of each helical RNA segment whose helical axis is along the edge of the icosahedron. The helical RNA segments are seven base-pairs in length with a stacked base at each 3' end so that a total of 16 nucleotides is clearly visible. The character of the RNA helix is somewhat different than any of the canonical forms. Assuming full occupancy, then approximately 45% of the total RNA genome is present in the electron density map. The close association of capsid with highly structured nucleic acid suggests that assembly of STMV is likely to be a highly co-operative process involving both protein and RNA. The nucleic acid is distributed within the virion with a high degree of order. The capsid protein is a true double helical RNA binding protein and a number of prominent interactions between protein and RNA can be clearly seen. PMID- 8510154 TI - Distribution of solvent molecules around apolar side-chains in protein crystals. AB - We have analysed the distribution of solvent sites within 5.0 A of the apolar side-chains alanine, valine, leucine, isoleucine and phenylalanine based on experimental data from 24 high-resolution protein structures. Clustering of solvent molecules into specific regions can be seen superimposed on a broad background of sites. The non-random nature of these distributions is confirmed by quantitative analysis of the solvent sites according to a spherical polar (r, theta and phi) co-ordinate system with the apolar atom of interest at the centre. One of the general features of these solvent sites is that they peak at around 4.0 A from an apolar protein carbon atom. Preferences in orientation (theta and phi) are also seen in the solvent distributions especially around the alanine CB atom and the phenylalanine ring. Most (around 75%) of the solvent sites around apolar groups are also within hydrogen bonding distance of protein (main chain) polar groups which leads to a distribution dependent on the local secondary structure. The remaining 25% of solvent sites are referred to as "non-polar" water molecules and their crystallographic temperature factors are higher than average by between 15% to 28%. For alanine and phenylalanine there are enough data to show that water molecules not within hydrogen bonding distance of protein polar atoms also cluster into specific regions. However, the main conclusion appears to be that the hydrophobic hydration in protein crystals is correlated with hydration of polar groups and thus depends on the local environment as well as on the stereochemistry of the apolar atoms. PMID- 8510155 TI - High resolution crystal structure of the A-DNA decamer d(CCCGGCCGGG). Novel intermolecular base-paired G*(G.C) triplets. AB - The DNA decamer d(CCCGGCCGGG) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 24.88, b = 44.60 and c = 46.97 A containing a duplex in the asymmetric unit. The structure was solved by molecular replacement and refined to an R factor of 18.5% using 6033 reflections at 1.65 A resolution. The decamer duplex adopts an A-DNA conformation. The abrupt dislocation of the duplex at the fourth base-pair G(4).C(17) by an abutting symmetry related molecule results in distortion of the backbone bonds of the fifth residue G(5), P O(5')(alpha) and C(4')-C(5')(gamma), to the trans conformations from their favored gauche- and gauche+ conformations, respectively. In this close encounter the terminal G(10).C(11) base-pair of the symmetry related molecule hydrogen bonds to the G(4).C(17) base-pair forming a novel base-paired G(4)*(G10).C(11)) triplet, where G(4) is hydrogen bonded to both G(10) and C(11). To facilitate this hydrogen bonding the G(4).C(17) base-pair slides into the minor groove, causing a toll on the backbone conformation of the adjacent residue G(5). A similar triplet base-pairing interaction with somewhat weaker hydrogen bonds occurs at the pseudo dyad related C(7).G(14) base-pair with G(20) of another symmetry related duplex. This pseudo triplet interaction (C(7).G(14))*G(20), does not perturb the backgone alpha and gamma torsions of G(15). Both the novel base triplets are non-planar. The abrupt dislocation/bend at the G(4).C(17) base-pair jolts the global helical base-pair parameters, inclination, tilt, roll, tip, etc. quite markedly. Therefore a better description of the helix parameters is obtained by splitting the duplex and calculating the local helix axis for the top half consisting of the first three base-pairs, and the lower half consisting of the last six base-pairs, omitting the fourth base-pair. The two half duplexes are bent by only 10 degrees. This structure further demonstrates that crystal packing interactions, which can also be governed by base sequence, play a dominant role in determining DNA conformation. PMID- 8510156 TI - Refined crystal structure of human transforming growth factor beta 2 at 1.95 A resolution. AB - Transforming growth factor beta 2 (TGF-beta 2), a homodimeric protein, is a member of a family of structurally related polypeptides that regulate various growth and differentiation processes in many cell types. The crystal structure of recombinant human TGF-beta 2 has been determined using a single heavy-atom derivative, anomalous scattering and by applying solvent flattening. The molecular model has been refined by a combination of simulated annealing and restrained least-squares refinement to a crystallographic R-factor of 0.194 including all data from 1.95 A to 8.0 A resolution. In the final structure, the root-mean-square deviation for bond lengths is 0.007 A and for bond angles 1.97 degrees. The final model includes 890 protein atoms (all 112 amino acid residues) as well as 84 water molecules. The new monomer fold consists of a separate alpha helix and two pairs of antiparallel beta-sheet segments, which can be subdivided into nine individual beta-strands. The extended monomer lacks the typical hydrophobic core. A cluster of disulfide bridges, including the TGF-beta knot, connects the beta-strands with each other as well as the alpha-helix. Two monomers are covalently linked by a single disulfide bridge. In the dimer the alpha-helix of one subunit interacts with the beta-sheet of the other subunit forming two symmetrically related hydrophobic cores. The center of the dimer interaction is stabilized by a network of hydrogen bonds including several well defined water molecules, which surround the central intersubunit disulfide bridge. The refined structure reveals the details of hydrogen bonding, electrostatic and hydrophobic interactions between intra- and intersubunit residues and allows the identification of possible receptor binding segments. PMID- 8510157 TI - On the pH dependence of protein stability. AB - This paper treats the free energy contribution of ionizable groups to protein stability. A method is presented for the calculation of the pH dependence of the denaturation free energy of a protein, which yields results that can be compared directly to experiment. The first step in the treatment is the determination of the average charges of all the ionizable groups in both the folded and unfolded protein. An expression due to Tanford then relates the pH dependence of the unfolding free energy to the difference in net charge between the two states. In order to determine absolute rather than relative unfolding free energies, it is necessary to calculate the total contribution of ionizable groups to protein stability at some reference pH. This is accomplished through a statistical mechanical treatment similar to the one used previously in the calculation of pKas. The treatment itself is rigorous but it suffers from uncertainties in the pKa calculations. Nevertheless, the overall shape of experimentally observed plots of denaturation free energy as a function of pH are reasonably well reproduced by the calculations. A number of general conclusions that arise from the analysis are: (1) knowledge of titration curves and/or effective pKa values of ionizable groups in proteins is sufficient to calculate the pH dependence of the denaturation free energy with respect to some reference pH value. However, in order to calculate the absolute contribution of ionizable groups to protein stability, it is necessary to also know the intrinsic pKa of each group. This is defined as the pKa of a group in a hypothetical state of the protein where all other groups are neutral. (2) Due to desolvation effects, ionizable groups destabilize proteins, although the effect is strongly dependent on pH. There are however, strongly stabilizing pairwise Coulombic interactions on the surface of proteins. (3) Plots of stability versus pH should not be interpreted in terms of a group whose pKa corresponds to the titration midpoint, but rather to a group with different pKas (that correspond approximately to the titration end points) in each state. (4) Any residual structure in the GuHCl-denatured state of proteins appears to have little effect on the pH dependence of stability. (5) pH dependent unfolding, for example to the "molten globule" state, appears due to individual groups with anomalous pKas whose locations on the protein surface may determine the nature of the unfolded state. PMID- 8510158 TI - Sequence dependence of the free energy of B-Z junction formation in deoxyoligonucleotides. AB - The NaCl-induced transition from the right-handed B form to a hybrid form containing both left and right-handed DNA, joined by a B-Z junction, was investigated. Transition curves were constructed from circular dichroism spectra collected as a function of NaCl concentration for a series of 16 bp deoxyoligonucleotides. The sequence of the series (one strand of the duplex) was: 5'CGCGCGCGAMNGACTG, where C indicates m5dC, and -MN- was varied to include the possible Py:Py stacks: -CC-, -CT-, -TC- and -TT-. Transition curves for the conversion of all deoxyoligonucleotides were found to be biphasic. Singular value decomposition was used to analyze the experimental circular dichroism spectra obtained as a function of NaCl, and showed that the transition was not a simple two-state process, but rather required at least three species to account for the experimental data. A sequential three-state model, B<-->I<-->BZ, was derived and applied to analyze experimental transition curves. Non-linear least-squares analysis was used to evaluate the salt-dependent equilibrium constants for each step in the sequential reaction model. The results indicate that the free energy change for B-Z junction formation (delta Gj) depends on the dinucleotide sequence near the junction. At a Na activity of 5, delta Gj values ranging from +1.2 to +1.7 kcal mol-1 were determined, depending on the sequence near the junction. delta Gj was found to be strongly dependent on salt concentration, with its magnitude decreasing with increasing Na activity. In addition to studies on linear duplex molecules, the B to BZ transition was also investigated in "dumbbell" forms of selected sequences. In these molecules, the ends were covalently linked by a single-stranded T4 segment. These studies show that junction formation is energetically more costly in dumbbells than in their linear counterparts. A striking correlation was found between delta Gj and two independent conformational properties of the dinucleotide steps that were introduced into the linear duplex molecules. These are the free energy of unstacking and the estimated free energy change for the conversion of the dinucleotide from the B to the A conformation. The more stable against unstacking, or the more resistant to the B to A conversion, the sequence near the junction site is, the more costly is B-Z junction formation. These correlations reveal that the DNA sequence near the junction apparently must be pliable in order to accommodate the unusual structure of the junction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510159 TI - Crystallization and preliminary X-ray analysis of vipoxin, a complex between a toxic phospholipase A2 and its natural polypeptide inhibitor. AB - The toxin vipoxin, which is a complex between a basic toxic phospholipase A2 and an acidic non-toxic protein inhibitor, is found in the venom of the Bulgarian viper (Vipera ammodytes ammodytes), the most toxic snake in Europe. The two polypeptide chains each consist of 122 residues and are highly homologous (62%). The vipoxin complex is the first reported example of a high degree of structural homology between an enzyme and its natural inhibitor. The present crystals diffract in the X-ray beam to 1.8 A resolution. The space group is P2(1)2(1)2(1). The cell dimensions are a = 45.80 A, b = 55.36 A and c = 107.69 A. Native data to a resolution of 2.8 A have been recorded. PMID- 8510160 TI - Two-dimensional crystallization of the light-harvesting complex from Rhodospirillum rubrum. AB - Homogeneous detergent-solubilized B873 light-harvesting complexes from a carotenoid-less mutant of the purple non-sulfur bacterium, Rhodospirillum rubrum G9, were reassembled spontaneously into two-dimensional (2D) hexagonal arrays during extensive and controlled dialysis. As the complexes contain only 1 to 2 mol phospholipid per mol alpha beta dimer, the arrays formed by a self assembly process are primary due to protein-protein interactions. The hexagonal lattices were analyzed by negative stain electron microscopy and digital image processing. They exhibited a unit cell size of 12.3 nm, in close agreement with the particle diameter of the active photo-unit in native chromatophore membranes. The unit cell contains a central 5 nm stain-filled depression, embraced by a ring with an outer diameter of 10 nm. PMID- 8510161 TI - Preliminary analysis of crystals of 4-oxalocrotonate tautomerase, an enzyme composed of unusually small monomers. AB - Crystals of 4-oxalocrotonate tautomerase have been obtained by the vapor diffusion method using polyethylene glycol as precipitant. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell parameters a = 118.1, b = 95.6, c = 97.4, alpha = beta = gamma = 90 degrees and diffract well to at least 2.7 A resolution. There are approximately ten 6811 dalton subunits of the enzyme per asymmetric unit, giving a crystal solvent content of 70%. PMID- 8510162 TI - Segment substitutions in alpha satellite DNA. Unusual structure of human chromosome 3-specific alpha satellite repeat unit. AB - We have sequenced the full-length copy of the alpha satellite higher-order repeated unit characteristic of human chromosome 3. Its internal structure, the regular alterations of J1 and J2 type monomers, is typical of the alphoid suprachromosomal family 1. This dimeric order is disrupted by the substitution of one J1 unit by an alien dimer which is not clearly related to any of the established monomeric types. We have also observed some other similar cases of segment substitutions in alpha satellite DNA. They probably represent a special type of molecular event which could be generated by gene conversion. Segment substitutions may be one of the important factors responsible for the extreme variability of localization patterns and actual sequences of alpha satellite DNA that should be taken into account in reconstructions of alpha satellite evolution. PMID- 8510163 TI - Sequence and structure of a new coiled coil protein from a microtubule bundle in Giardia. AB - The flagellate Giardia is reportedly (and controversially) the most primitive eukaryotic organism known to us. The trophozoite is without organelles but has an extensive cytoskeleton of microtubules and associated structural proteins. We have cloned and sequenced overlapping cDNAs and genomic DNAs for a 101,000 M(r) protein involved in microtubule bundling in the median body of G. lamblia cells. The polypeptide chain appears to be mainly alpha-helical with the repeating amphipathic heptapeptides characteristic of a coiled coil molecule, but without homology to known microtubule-associated proteins. Domain analysis suggests a structure in which a rod of three linked coils spans 695 residues (approximately 103 nm), with the ends of the chain forming compact globular head and tail domains of approximately 11 kDa and approximately 7 kDa. The rod domain has internal sequence repeats of 24 residues caused by multiple phase shifts in the coiled coil heptapeptide positions. These repeats have a conserved side-chain pattern which contributes the most significant periodicities in Fourier transforms of the linear distributions of apolar and charged residues. Our best alignment of the pattern has 21 complete repeats of 24 residues and 9 partial repeats of 21 or fewer residues. The apolar residue phase shifts will produce a regular stutter in the hydrophobic core of the coiled coil. This structure is reminiscent of beta-giardin, another coiled coil protein with a broken seam found in the Giardia cytoskeleton. Although the underlying sequence motif is different for the two proteins, the general feature of being regularly divided into segments might relate to a similar mechanism of interaction with microtubules. PMID- 8510164 TI - Dense cluster of genes is located at the ecdysone-regulated 3C puff of Drosophila melanogaster. AB - The 3C11-12 polytene bands of the Drosophila melanogaster X chromosome give rise to a prominent puff, whose regression is triggered by the increase in the titre of the steroid hormone 20-hydroxyecdysone occurring before the metamorphosis. Here, we report the molecular characterization of three genes, named ng-2, ng-3 and ng-4, which we found to be closely linked to each other and to Sgs-4, Pig-1 and ng-1, three other genes previously mapped at this polytene region. All six genes are, in fact, arranged in a tightly linked cluster spanning a DNA segment of only 11 kb. With the exception of ng-4, all the clustered genes are highly expressed only during the larval life and share the same tissue-specificity, being mainly transcribed within the salivary glands. In addition, two members of the cluster, ng-1 and ng-2, show a very high degree of sequence homology, clearly indicating that they are related to each other by means of a duplication event. Interestingly to note, the entire cluster shows a peculiar genomic location, extending across two introns of the memory gene dunce, a large gene of Drosophila whose organization has proved to be remarkably complex. PMID- 8510165 TI - The CUB domain. A widespread module in developmentally regulated proteins. AB - Sequence analysis has revealed the presence of 31 copies of an extracellular domain, here called CUB, in 16 functionally diverse proteins such as the dorso ventral patterning protein tolloid, bone morphogenetic protein 1, a family of spermadhesins, complement subcomponents Cls/Clr and the neuronal recognition molecule A5. Most of them are known to be involved in developmental processes. Our analysis of this new family includes the identification of seven previously undescribed members, the characterization of conserved features and a topology prediction of this approximately 110 residue spanning domain, which suggests an antiparallel beta-barrel similar to those in immunoglobulins. PMID- 8510166 TI - Accumulation of intracellular chloride by (Na-K-Cl) co-transport in rat arterial smooth muscle is enhanced in deoxycorticosterone acetate (DOCA)/salt hypertension. AB - The accumulation of intracellular chloride above equilibrium by (Na-K-Cl) co transport has been demonstrated in a variety of tissues, most recently in guinea pig vas deferens. The depolarizing influence of the co-transporter on the membrane potential of arterial smooth muscle cells has been demonstrated in rat femoral artery. The inference is that the depolarisation of membrane potential seen in deoxycorticosterone acetate (DOCA)/salt hypertension is the result of increased chloride accumulation via (Na-K-Cl) co-transport, which is enhanced in hypertension. The questions addressed here are (i) whether chloride is accumulated above equilibrium in saphenous arterial smooth muscle cells from normotensive animals, and (ii) whether the accumulation is more pronounced in association with DOCA/salt hypertension. In arterial smooth muscle from DOCA/salt hypertensive animals, [Cl-]i was significantly elevated (P < 2 x 10(-9)) in comparison to arterial smooth muscle from normotensive control animals. The loop diuretic bumetanide caused a reversible hyperpolarization of Em and a fall in [Cl ]i and these effects were enhanced in hypertension. These results are consistent with an increase in the activity of the (Na-K-Cl) co-transporter in rat femoral arterial smooth muscle in DOCA/salt hypertension. A preliminary report of this work has been published. PMID- 8510167 TI - A new cardiotonic drug reduces the energy cost of active tension in cardiac muscle. AB - The novel thiadiazinone EMD 57033 (EMD) increases the calcium responsiveness of the contractile proteins in cardiac muscle. In skinned ventricular trabeculae isolated from guinea-pig heart, application of 10 microM EMD shifted the curve relating isometric tension to the applied calcium concentration to the left and increased maximal tension by 15%. In intact trabeculae, the rate of heat production, an indicator of the rate of ATP hydrolysis in the steady state, and isometric tension were measured at 37 degrees C. Both the thiadiazinone (EMD; 2.5, 5, and 10 microM) and the cardiac glycoside dihydro-ouabain (DHO; 5, 10, and 20 microM) produced a concentration-dependent increase in contraction-related heart production (Hc) and in the tension time integral of isometric contractions (Tti). In the presence of EMD the energy cost of active tension (Hc/Tti) was substantially decreased as compared to control conditions. The energy cost of the positive inotropic effect of EMD (43.8 mW N-1 cm-1) was only about half as large as the energy cost of the positive inotropic effect of DHO (88.4 mW N-1 cm-1). It is concluded that EMD causes a change in cross-bridge kinetics that increases the contractility of cardiac muscle and improves the economy of chemo-mechanical energy transduction. Our results suggest that EMD 57033 represents a prototype of a new class of cardiotonic agents that might be potentially useful in the therapy of congestive heart failure. PMID- 8510168 TI - Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2. AB - The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone. PMID- 8510169 TI - The functional recovery of post-ischemic myocardium requires glycolysis during early reperfusion. AB - Glycolysis normally provides only a small fraction of myocardial ATP production, but ATP from glycolysis may be preferentially used to support membrane activities such as ion pumping. Since ion homeostasis is disturbed during ischemia, glycolysis may be particularly important in the recovery of postischemic myocardium. This hypothesis was investigated in isovolumic, isolated rabbit hearts, perfused with 16 mM glucose, 5 mM pyruvate or 5 mM acetate. Global left ventricular function (rate-pressure product, RPP) and unidirectional ATP synthesis rate (P(i)-->ATP flux, 31P NMR) were measured before and after 20 min global ischemia. Control hearts with intact glycolysis were compared with hearts which had glycolysis inhibited by iodoacetate (150 microM), 2-deoxyglucose (10 mM) or prior glycogen depletion. In normal hearts, inhibition of glycolysis had no effect on function when pyruvate or acetate was present as as a carbon substrate. In post-ischemic hearts, reperfusion with glucose (n = 7) resulted in moderate recovery of function to about 65% of pre-ischemic levels after 1 h reperfusion. Administration of iodoacetate at the onset of reperfusion to hearts receiving pyruvate or acetate resulted in much worse functional recovery and a marked rise in left ventricular end-diastolic pressure (LVEDP). With pyruvate (n = 7), RPP recovered to 27% of pre-ischemic levels, while mean LVEDP increased to 34 mmHg (vs 16 mmHg with glucose); with acetate (n = 6), RPP returned to 31% of pre-ischemic levels, while mean LVEDP rose to 32 mmHg. The ratio of P(i)-->ATP flux to atoms of oxygen consumed (P:O ratio) was 2.14 +/- 0.36 in hearts reperfused with iodoacetate and pyruvate, consistent with partial mitochondrial uncoupling. However, if inhibition of glycolysis with iodoacetate was delayed until after 30 min reperfusion, recovery of hearts reperfused with pyruvate was similar to hearts perfused with glucose, and there was no evidence of mitochondrial uncoupling (P:O ratio = 2.95 +/- 0.33). Inhibition of glycolysis during reperfusion with 2-deoxyglucose yielded results similar to reperfusion with iodoacetate. The worst recovery was observed in hearts with combined glycolytic inhibition by pre-ischemic glycogen depletion and iodoacetate during reperfusion (RPP = 13% of pre-ischemic levels). These findings indicate that glycolysis plays a crucial role during early reperfusion in the functional and metabolic recovery of post-ischemic myocardium. PMID- 8510170 TI - [32P]phosphate autoradiography as an indicator of regional myocardial oxygen consumption? AB - The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insoluble and soluble material and total tissue was determined. Oxygen uptake and perfusion pressure were continuously monitored. For control hearts the rate of incorporation of radioactivity into all four fractions was linear. Isoproterenol and pressure loading each increased total 32Pi uptake rate and the incorporation rate of 32Pi into ATP. Significant positive correlations were noted between the rates of total 32Pi uptake and oxygen uptake (r = 0.895; P < 0.001) and between the rates of 32P incorporation into ATP and oxygen uptake (r = 0.890; P < 0.001). Autoradiography of diffusible radioactive material (representing total 32Pi uptake) indicated that label correlated with oxygen uptake (r = 0.850; P < 0.001) and was distributed uniformly across the ventricle wall. Hearts subjected to 30 min of regional ischemia followed by reperfusion were indistinguishable from the control group in terms of either total 32Pi uptake or total oxygen uptake, but showed a marked necrotic area that was unlabeled surrounded by an area that was intensely labeled. It is concluded that autoradiography of diffusible radioactive material representing total 32Pi uptake may be applicable for assessing regional myocardial oxygen uptake. The technique has identified a region of tissue in reperfused ischemic hearts that surrounds necrotic tissue and which may have a compensatory increase in a oxidative metabolism. PMID- 8510171 TI - Trans-cellular desmin-lamin B intermediate filament network in cardiac myocytes. AB - Excessive stretch of heart muscle is thought to be a determinant of myocardial hypertrophy. Because cell shape and nuclear shape are closely coupled in cardiac myocytes, we hypothesize that excessive stretch causes physical deformation of the nucleus which might be responsible for some molecular events leading to hypertrophy. Cell shape and nuclear shape are most likely to be coupled by cytoskeletal elements. With this in mind, we have used immunogold labeling to examine the topological associations of desmin cytoskeletal and lamin B nucleoskeletal intermediate filaments with various intracellular structures in mammalian cardiac myocytes. We found that desmin filaments form a sarcoplasmic network radiating from the sarcolemma to the nuclear surface. Perpendicular to the long axis of the cell, strands of desmin filaments traverse the interfibrillary space in a co-linear arrangement with Z-discs. The desmin filament strands extend between peripheral regions of adjacent Z-discs. Desmin filaments traversing the interfibrillary space closely associate with the surface of mitochondria. At the cell surface, desmin filaments extend from Z-discs to terminate immediately beneath the sarcolemma. Close to the nucleus, desmin filaments extend from Z-discs towards nuclear pores. At the same time, lamin B filaments, which co-localize with heterochromatin immediately beneath the inner nuclear membrane, encircle the inner aspect of each nuclear pore. We hypothesize that desmin and lamin B are functionally anchored to each other at the nuclear pore, either directly or through anchorage proteins within the pore complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510172 TI - Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a G-protein mechanism. AB - We tested whether a pertussis toxin-sensitive G-protein mediates the protective effects of preconditioning. Thirty-one small (1 kg) rabbits were used. All rabbits experienced 30 min regional myocardial ischaemia followed by 3 h reperfusion. Infarct size was determined by tetrazolium. The percentage of the risk zone which infarcted in controls was 37.4 +/- 4.6%. Preconditioning with a 5 min occlusion followed by 10 min reperfusion prior to the 30 min ischaemic insult protected against infarction (5.2 +/- 2.1% infarction). 25 micrograms/kg pertussis toxin, administered 48 h prior to surgery, blocked G-protein signal transduction as tested by challenge with iv acetylcholine which normally slows the heart. Pertussis toxin treatment had no effect on infarct size in non preconditioned rabbits (37.6 +/- 4.7% infarction) but blocked protection in preconditioned rabbits (27.3 +/- 4.3% infarction). To test the involvement of G proteins further in preconditioning, we tested the ability of the M2 agonist carbachol to substitute for ischaemic preconditioning and protect the heart from infarction. Rabbits hearts were excised and perfused with Kreb's buffer. Control animals subjected to 30 min of regional ischaemia and 2 h reperfusion yielded 29.4 +/- 2.9% infarction. Preconditioning with 5 min global ischaemia and 10 min reperfusion prior to the 30 min regional ischaemia significantly protected the isolated heart from infarction (8.41 +/- 3.26% infarction). Carbachol, infused for 5 min at 1 microM concentration, protected the hearts as well as preconditioning, yielding 8.90 +/- 2.08% infarction. We conclude that preconditioning involves a pertussis toxin-sensitive G-protein and that the same G-protein couples to muscarinic M2 receptors. PMID- 8510173 TI - The cardiac form of the tissue-specific SmN protein is identical to the brain and embryonic forms of the protein. AB - The SmN protein is a component of small nuclear ribonucleoprotein particles and closely related to the ubiquitously expressed SmB and B' splicing proteins. However, SmN is only expressed in a limited range of tissues and cell types such as brain, heart and early embryonic cells. The isolation of cDNA clones derived from the mRNA encoding SmN in different cell types has indicated that the brain and embryonic forms of the protein are identical and are encoded by a distinct gene to that encoding SmB and B'. It has been suggested however, that the cardiac form of SmN is encoded by a distinct mRNA which is derived from a different gene from that encoding the brain and embryonic forms of SmN. By using the polymerase chain reaction as well as cDNA cloning we have shown that this is not the case and that the cardiac, brain and embryonic forms of the protein are identical and are translated from the same mRNA encoded by a single gene. The significance of this finding is discussed in terms of the complex expression pattern of this gene and the possible functional role of SmN. PMID- 8510174 TI - Xth Meeting (Japanese section) of the International Society for Heart Research. Oita, Japan, 4-5 June 1993. Abstracts. PMID- 8510175 TI - XVth Meeting (American Section) of the International Society for Heart Research. Missouri, USA, 20-24 June 1993. Abstracts. PMID- 8510176 TI - Neutral adaptation of the genetic code to double-strand coding. AB - We lay new foundations to the hypothesis that the genetic code is adapted to evolutionary retention of information in the antisense strands of natural DNA/RNA sequences. In particular, we show that the genetic code exhibits, beyond the neutral replacement patterns of amino acid substitutions, optimal properties by favoring simultaneous evolution of proteins encoded in DNA/RNA sense-antisense strands. This is borne out in the sense-antisense transformations of the codons of every amino acid which target amino acids physicochemically similar to each other. Moreover, silent mutations in the sense strand generate conservative ones in its antisense counterpart and vice versa. Coevolution of proteins coded by complementary strands is shown to be a definite possibility, a result which does not depend on any physical interaction between the coevolving proteins. Likewise, the degree to which the present genetic code is dedicated to evolutionary sense antisense tolerance is demonstrated by comparison with many randomized codes. Double-strand coding is quantified from an information-theoretical point of view. PMID- 8510177 TI - Immunoglobulin heavy chain constant and heavy chain variable region genes in phylogenetically diverse species of bony fish. AB - Genomic DNA from 18 phylogenetically diverse species of bony fish was hybridized with probes specific for the channel catfish immunoglobulin heavy chain constant (CH) gene, as well as with immunoglobulin heavy chain variable (VH) probes specific for five channel catfish VH gene families. The results showed that CH probes strongly hybridized only to genomic fragments from other catfish species. In contrast, restricted DNA from most other species hybridized with at least two channel catfish VH probes. In those species whose DNA hybridized with multiple VH probes, the restriction pattern of hybridizing fragments was probe-dependent. These studies suggest that (1) the CH gene defined in channel catfish appears to share similarity only with CH genes in other catfish species, (2) families of VH genes appear to have diverged in early phylogenetic lineages of teleosts, and (3) VH genes similar to those defined in catfish appear to be widely represented in phylogenetically diverse species of teleosts. PMID- 8510178 TI - Divergent evolution may link human immunodeficiency virus GP41 to human CD4. AB - A local sequence similarity of HIV envelope proteins (gp120 and gp41) to immunoglobulins suggests that a mimicry phenomenon may form the basis of the HIV cell membrane interaction and of HIV-induced autoimmune reaction. We explored the hypothesis of any deeper relationship between HIV env proteins and immunoglobulin family members. An overall DNA sequence similarity between gp41 coding region of env gene and the HIV-receptor CD4 gene was observed and a 14-base-long oligonucleotide, almost unique in the GenBank, was found in gp41 and CD4 genes. The alignment of env gene to CD4 gene and to 84 different sequences showed a significantly higher homology score and a nonrandom similarity in the CD4-env alignment. A significant similarity was also found between the env protein and the sequence encoded by an alternate reading frame of CD4 gene. Our observations suggest that gp41 coding region might have a different origin than the gp120 coding region of the env gene, and that a divergent evolution might link gp41 to CD4 or immunoglobulin family members. In this study the analysis of alternate reading-frame products is also proposed as a novel approach to investigate evolutionary links and structure-function relationships. PMID- 8510181 TI - Evolution of EF-hand calcium-modulated proteins. V. The genes encoding EF-hand proteins are not clustered in mammalian genomes. AB - The chromosomal assignments of genes belonging to the EF-hand family which have a common origin are compiled in this article. So far data are available from 27 human gene loci belonging to 6 subfamilies and 8 murine loci belonging to 4 subfamilies. Chromosomal localization has been obtained by somatic-cell hybrid analysis using the Southern blot technique or PCR amplification, metaphase spread in situ hybridization, or isolation of the particular genes from chromosome specific libraries. Except for genes of the S-100 alpha proteins which are grouped on human chromosome 1q12-25 and mouse chromosome 3, no linkage has been found for genes encoding EF-hand proteins, indicating absence of selective pressure for maintaining chromosomal clustering. Six of these genes map to known syntenic groups conserved in the human and mouse genomes. This suggests that chromosomal translocations occurred before divergence of these species. The possible significance of chromosomal positioning with respect to nearby located known genes and genetic disease loci is discussed. PMID- 8510182 TI - Association of glucocorticoid receptor immunoreactivity with cell membrane and transport vesicles in hippocampal and hypothalamic neurons of the rat. AB - The aim of the present study was to reveal at the ultrastructural level cytoplasmic loci that display glucocorticoid receptor (GR) immunoreactivity in pyramidal neurons of the CA1 sector of the hippocampus and in cells of the medial parvicellular subnucleus of the hypothalamic paraventricular nucleus (PVN). Adrenalectomized male rats were injected intraperitoneally with corticosterone (CS) (1 mg/100 g bw) and sacrificed within 4 hr. Vibratome sections of the perfusion-fixed forebrains were processed for immunocytochemical detection of type 2 GR by means of the BuGr, anti-rat liver GR monoclonal antibody and silver gold-intensified diaminobenzidine chromogen. The corticosterone administration gradually shifted the GR immunoreactivity (IR) from the cytoplasm to the nucleus. Samples taken 20-40 min after the steroid treatment demonstrated pyramidal cells expressing GR IR in both the cytoplasmic and nuclear pools. Although the chromatin-associated appearance of GR in the nucleus was identifiable at the light microscopic level, the nature of immunoreactive intracytoplasmic loci was not. Ultrastructural analysis of the cytoplasm indicated that fine silver-gold grains marking GR-immunoreactive sites associated with the plasma membrane and coated and regular vesicles. Noted occasionally beneath the plasma membrane of the cell bodies and dendrites, the vesicles also appeared at deeper locations in dendritic processes and around the cell nuclei. These results suggest that glucocorticoid receptors participate in signal transduction at the level of the cell membrane, as well as at the level of the genome in the cell nucleus. PMID- 8510180 TI - Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins. AB - In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences. PMID- 8510179 TI - Evolution of EF-hand calcium-modulated proteins. III. Exon sequences confirm most dendrograms based on protein sequences: calmodulin dendrograms show significant lack of parallelism. AB - In the first report in this series we presented dendrograms based on 152 individual proteins of the EF-hand family. In the second we used sequences from 228 proteins, containing 835 domains, and showed that eight of the 29 subfamilies are congruent and that the EF-hand domains of the remaining 21 subfamilies have diverse evolutionary histories. In this study we have computed dendrograms within and among the EF-hand subfamilies using the encoding DNA sequences. In most instances the dendrograms based on protein and on DNA sequences are very similar. Significant differences between protein and DNA trees for calmodulin remain unexplained. In our fourth report we evaluate the sequences and the distribution of introns within the EF-hand family and conclude that exon shuffling did not play a significant role in its evolution. PMID- 8510183 TI - Widespread constitutive expression of HSP90 messenger RNA in rat brain. AB - The distribution of constitutively expressed mRNA encoding 2 isoforms of heat shock protein 90 (HSP90) was investigated in adult rat brain by in situ hybridization with 35S-labeled cRNA probes. HSP90 mRNA density was estimated by semiquantitative autoradiography and by microscopic analysis. The distribution of HSP90 transcripts was similar for the 2 probes. HSP90 mRNA was widespread but not ubiquitous, and labeling intensity varied among different regions. In particular, HSP90 mRNA was abundant in limbic system-related structures, such as the hippocampus, amygdala, mamillary body, piriform cortex, enthorhinal cortex, bed nucleus of the stria terminalis, medial habenular nucleus, and preoptic hypothalamic nuclei. The highest abundance of mRNA was detected in the Purkinje cell layer of the cerebellum. High abundance was also present in pineal body, choroid plexus, cerebellar granule cell layer, and cranial nerve nuclei. HSP90 mRNA was present in moderate abundance throughout the cortical gray mantle, in the caudate-putamen, most other thalamic and hypothalamic nuclei, the pontine and spinal gray matter, and the anterior lobe of the hypophysis. Weak hybridization was observed in white matter fiber tracts, glial cells, and leptomeninges, and none was observed in endothelial cells and the smooth muscle of the cerebral microvasculature. Our findings suggest that HSP90 gene products may serve constitutive neuron-specific functions in the unstressed brain. PMID- 8510184 TI - Effects of nerve growth factor on the survival of primary cultured adult and aged mouse sensory neurons. AB - This study investigated the effects of exogenous nerve growth factor (NGF) on the survival and differentiation in primary culture of sensory neurons isolated from adult (6 months) and aged (2 years) mice. For neurons prepared from adult mice, a concentration effect was evident during a 2 week culture period: Neuronal counts in cultures supplemented with 25 and 50 ng/ml NGF did not differ significantly from those of control cultures without exogenous NGF or those with anti-NGF included in the culture medium, whereas cultures supplemented with either 100 or 200 ng/ml NGF contained higher numbers of neurons throughout the culture period. Cultures prepared from aged mice contained less neurons than those from adult mice, although those supplemented with 100 ng/ml NGF retained higher neuronal numbers than cultures from aged mice which did not receive exogenous NGF. Neuronal diameters were measured to investigate whether specific subpopulations of neurons were more dependent on NGF; the results indicate that neurons of a medium-larger diameter were more prevalent than cells with a smaller diameter following NGF administration. A shape index was calculated for each culture regimen; with longer culture periods a higher proportion of spindle-shaped neurons was observed. PMID- 8510185 TI - Identification of membrane-bound carbonic anhydrase in white matter coated vesicles: the fate of carbonic anhydrase and other white matter coated vesicle proteins in triethyl tin-induced leukoencephalopathy. AB - We have extended our studies on the content of white matter derived coated vesicles (WMCVs) to show that they are enriched in membrane-bound carbonic anhydrase. Within the myelin complex membrane-bound carbonic anhydrase is concentrated in the periaxolemmal domain; however, this protein is enriched almost sevenfold in the bilayer of coated vesicles even relative to this myelin membrane region. These data suggest that some vesicles are derived from a site at which this enzyme is highly localized. The enrichment observed for membrane-bound carbonic anhydrase is unique since other periaxolemmal proteins such as CNPase and plasmolipin are only present in equal amounts in periaxolemmal-myelin fractions and WMCVs. Based on their known localization, the presence of CNPase coupled with the absence of MAG in WMCVs suggest that these vesicles are derived from the paranodal region. The identification in WMCVs of periaxolemmal-myelin proteins associated with ion and fluid movement, such as carbonic anhydrase, Na+,K+ ATPase, and the putative K+ channel protein plasmolipin, prompted us to examine the status of these vesicles in triethyl tin (TET)-induced myelin edema. Coated vesicles and other membrane fractions were isolated from whole brains of control and TET-treated rats. Whole brains were used so we could compare the effects of TET on WMCV proteins with the effect on proteins enriched in gray matter coated vesicles. The results indicated that TET had no detectable effect on compact or periaxolemmal-myelin, however, Western blot analysis showed that WMCV proteins, such as carbonic anhydrase, CNPase, and plasmolipin, were virtually absent or greatly diminished from the whole brain coated vesicle fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510187 TI - Special issue. Towards a broader view of recovery: integrating nicotine addiction and chemical dependency treatments. PMID- 8510186 TI - Expression of the rat brain creatine kinase gene in C6 glioma cells. AB - We have recently shown that while brain creatine kinase (CKB) mRNA was detectable in RNA from cultured primary rat brain neurons, CKB mRNA was about 15-fold higher in primary astrocytes and 17-fold higher in oligodendrocytes (Molloy et al., J Neurochem 59:1925-1932, 1992). To begin to understand the molecular mechanisms responsible for brain glial cells containing the highest levels of CKB mRNA in the body, we have examined the expression of rat CKB mRNA in established C6 glioma cells. RNase-protection analysis showed the endogenous CKB mRNA levels in exponentially growing C6 were high and measured 50% of that in total RNA from rat brain lysate and 60% of that in cultured primary astrocytes and oligodendrocytes. The 5' and 3' ends of CKB mRNA in C6 were mapped to the same nucleotides as CKB mRNA from rat brain, indicating that the sites of in vivo transcription initiation and termination/polyadenylation of CKB mRNA in C6 are the same as in total rat brain RNA. The level of CKB enzyme activity in C6 whole cell lysates was among the highest of the glial cell lines which we measured. All creatine kinase enzyme activity present in C6 was found in the dimeric CKB isoform (BB), which is characteristic of CKB expression in the brain. A 2.9 kb gene fragment containing the basal CKB promoter and far-upstream 5' sequences was cloned upstream of the chloramphenicol acetyltransferase (CAT) gene and transfected into C6 cells. CAT activity was readily detectable in C6 and mapping of the 5' end of the CAT mRNA showed that transcription was directed from the correct initiation site. Since we found C6 cells were difficult to transfect, conditions were established which both maximized transfection efficiency and maintained normal C6 cell morphology. These results should permit the future identification of the nuclear trans-acting factors and the cognate cis-acting regulatory elements responsible for high CKB mRNA expression in brain glial cells. PMID- 8510188 TI - Confronting nicotine dependency at the Gateway Rehabilitation Center. AB - Gateway Rehabilitation Center, the largest addiction treatment center in Western Pennsylvania, struggled with the questions of nicotine dependence for many years. It developed what was thought to be a comprehensive nicotine treatment program and became totally smoke free on October 2, 1989. The following narrative describes Gateway's rationale and plan to become smoke free, the reasons for their "retreat," and their continued efforts to address nicotine dependence. PMID- 8510189 TI - Initial encounters with tobacco cessation on the Inpatient Substance Abuse Unit of the Medical College of Virginia. AB - When the Medical College of Virginia became a smoke-free facility on May 1, 1990, the inpatient unit of the Division of Substance Abuse Medicine decided that it would require tobacco abstinence of its patients, and that it would treat nicotine addiction in a similar fashion as other chemical dependencies. Surreptitious alcohol and drug use on the unit was minimal, but clandestine cigarette smoking prevailed. The succeeding restrictive environment and enforcement efforts became counterproductive. Beginning December 23, 1990, the inpatient unit decided to re-allow smoking. A motivational curriculum for all patients and an optional cessation program for those patients who wish to quit smoking during their inpatient stay is planned. Methods to effectively address nicotine addiction during chemical dependency treatment need to continually be refined and explored. PMID- 8510190 TI - Neurobehavioral mechanisms of nicotine action: role in the initiation and maintenance of tobacco dependence. AB - Basic neuroscience research conducted over the last quarter century has provided us with much information concerning potential biobehavioral and neuromolecular mechanisms involved in the initiation and maintenance of tobacco dependence. Nicotinic-acetylcholinergic receptors (AChRs), in addition to having a primary locus on cholinergic neurons, appear to be also located on a variety of noncholinergic neurons (presynaptic and/or postsynaptic sites). Nicotine therefore appears to be able to affect a variety of neuronal pathways involved in behavioral reward and arousal processes, which appear paramount to tobacco dependence. Nicotine appears to have several unique properties at the cellular level that allow it to act both as an agonist and as a potential antagonist at select AChRs. Nicotine's ability to act as an agonist appears to be contingent on an action at nAChRs, which initially open a receptor-linked cation channel, eliciting the entrance of CA++ (or other cations) into the cell. Cation entrance into the cell, therefore, may be the cellular transducer of nicotine's behavioral and dependence-producing effects. Subsequent to this initial agonist effect, the nicotinic receptor is believed to undergo a refractory period, via a desensitization process, during which Ca++ is prevented from further entrance into the cell. It is this ability to induce receptor desensitization which seems central to nicotine's ability to act as an antagonist. The duration of nAChR desensitization may also be useful in explaining individual variability to nicotine's behavioral effects and may be related to the induction of acute and/or chronic tolerance in both animals and man. Nicotine-induced desensitization may also be important to relapse in the smoker if conditioned stimuli are able to provoke such mechanisms, which could lead to the need to smoke. Finally, a model is presented to account for individual smoking patterns and level of tobacco dependence which is partially based on the proposed cellular mechanisms of nicotine action and desensitization at the nAChR. PMID- 8510191 TI - Patterns of alcohol, cigarette, and caffeine and other drug use in two drug abusing populations. AB - Relationships were explored among the frequencies of use of various drugs by a sample of drug-abusing clients of the Addiction Research Foundation (ARF) in Toronto and by drug abusers volunteering to participate in research at the Addiction Research Center (ARC) in Baltimore. The two groups of drug-abusing individuals differed in a number of characteristics. Those from ARF were admitted primarily for diagnosis and possible treatment for alcohol and non-opioid drug problems, whereas those from the ARC were admitted for participation in research on other drugs of abuse, primarily involving opioids. Patterns of use of certain drugs tended to covary in both groups. Of particular interest was the finding that severity of alcoholism was directly related to various measures of tobacco and caffeinated beverage use. In contrast, there was little correlation between the frequency of use among other drugs of abuse (e.g., heroin, cannabis, glue) and the use of tobacco and caffeine. These findings suggest that dependence on nicotine, caffeine, and alcohol may be governed by the same factors and possibly should be considered jointly in the treatment of alcoholic persons. Frequency of use of other drugs examined may be controlled by other factors than those which determine level of use of tobacco and caffeine. PMID- 8510192 TI - Treatment of smoking cessation in smokers with past alcohol/drug problems. AB - A review of existing scientific studies suggests (1) smoking is very common among alcoholics, (2) many recovering alcoholics die from smoking-related diseases, (3) recovering alcoholics are interested in smoking cessation, (4) recovering alcoholics can stop smoking, (5) smoking cessation does not appear to increase relapse to alcohol, and (6) possible treatments for smoking cessation among alcoholics have not been empirically tested. In a prior study of ours on nicotine gum, the 38 subjects (12% of the sample) who self-reported a past but not present history of alcohol/drug problems appeared more dependent on nicotine, were less likely to stop smoking (1 year quit rates = 7 vs. 19%) but appeared to benefit more from nicotine replacement therapy (+10 vs. +1% increase in 1 year quit rates with nicotine vs. placebo gum) than subjects without this history. Although these results are preliminary, they suggest recovering alcoholics might benefit from nicotine replacement therapy. PMID- 8510193 TI - When to begin smoking cessation in substance abusers. AB - During the past several years, there has been an increasing recognition and acceptance that the use of tobacco products often produces nicotine dependence and nicotine addiction. Despite this, the substance abuse treatment community has been slow to promote smoking cessation for patients who are in substance abuse treatment for another addiction. Dogma, although starting to change, persists that cigarette smoking pales in comparison to other addictions and should not be addressed at the time of initial treatment for another addiction. The limited research to date, which will be reviewed in this article, does not support this dogma. In addition, patients presenting for substance abuse treatment report high interest in stopping smoking, including interest in stopping when they initially present for substance abuse treatment. PMID- 8510194 TI - Protection from job bias for people who smoke. PMID- 8510195 TI - Flow cytometric DNA analysis of advanced prostatic adenocarcinoma. AB - Thirty-two patients with extracapsular invasive prostatic adenocarcinoma were analysed to investigate the prognostic significance of DNA flow cytometry by using the nuclear material extracted from paraffin embedded prostatectomy specimens. The DNA ploid pattern was diploid in 61% of the tumors and aneuploid in 39%. A significant correlation between the DNA diploid pattern with pathologic low grade tumors and the DNA aneuploid pattern with high stage tumors was not proved. The clinical stage correlated well with patients survival but only DNA ploidy pattern and pathologic grade had trends of correlation. However, if only the stage D tumors were analysed, a significant prognostic predictive value of DNA flow cytometry was identified. Although the results maybe regarded as preliminary, (in view of the small number of patients), these suggest that DNA content from the initial surgical samples provide only a synergistic effect to the clinical stage and pathologic grade in the prognostic evaluation of the advanced prostate cancers especially for those who underwent hormonal therapy postoperatively. PMID- 8510196 TI - Alteration of amino acid in plasma and cerebrospinal fluid of children with seizure disorders. AB - Amino acid levels in plasma were measured by amino acid autoanalyser in 130 convulsive children. The levels of taurine, serine and tryptophan were significantly lower in convulsive children as compared to normal control; in contrast, isoleucine, homocystine, GABA, histidine, arginine and ammonia were higher. The children with paroxysmal disorders (headache, dizziness and abdominal epilepsy) had the highest levels of isoleucine, histidine and arginine and the lowest levels of glutamate and cystein. Clinical seizure activity within 6 months prior to the test seemed to have no obvious effect on the plasma amino acid pattern, except for the levels of glycine and arginine tended to return to normal, and the level of GABA was significantly increased in patients with the seizure being controlled. The patients treated with carbamazepin as a single anticonvulsant had the highest GABA level compared to those with other anticonvulsants. Hyperglycinemia and hyperammonaemia were also noted in patients who took valproic acid. The levels of serine, isoleucine and phenylalanine in the CSF within 6 hours after convulsion were significantly lower than the normal control; while asparagine, tyrosine, lysine and arginine were significantly higher. The concentration of ammonia in the CSF was also elevated after convulsion as compared to the normal control. Amino acids play an important role in the generation of epilepsy and recently there has been an increasing number of studies to help determine their effects during an epileptic attack. However, there still is much debate and controversy on this topic. Therefore, further studies are needed and researchers should carefully consider factors that might affect the accurate assessment of the results. PMID- 8510197 TI - Ventricular tumors--CT evaluations of 28 cases. AB - Ventricular neoplasms can be grouped together as a single disease entity because of the behavior of some of the tumors and similarities between the access of therapy and procedure of operation. In our series, the incidence of various ventricular neoplasms (shown in decreasing order) were metastasis, astrocytoma, ependymoma, meningioma, choroid plexus papillomas and oligodendroglioma. The intraventricular tumors included some metastasis involved by hematogenous spread, meningioms, and choroid plexus papilloma while paraventricular tumors included some of the systemic myeloproliferative disorders with ventricular seeding along with tumors with glial origins. Most of the patients with symptoms of intraventricular tumors also had symptoms related to increased intracranial pressure while those with paraventricular neoplasm presented symptoms related to focal signs or symptoms. CT scan with enhancement could provide a very good image modality except in some involvements in the posterior cranial fossa. PMID- 8510198 TI - Management of windshield facial injuries. AB - Between Jan. 1986 and Dec. 1990, 99 patients with automobile windshield facial injuries were hospitalized in Kaohsiung Medical College hospital. All patients were injured by old type windshields in car accidents. Seventy-three patients (74%) were male and twenty-six (26%) were female. Ages ranged from 6 to 62 years (mean age 31 years). Fifty-seven patients (58%) were car drivers and forty-two (42%) were front seat passengers. All patients had typical multiple U-shaped lacerations on the face. The major injury sites were localized to the upper one third of the face. The wounds were repaired immediately after careful debridement. A total of 21 facial bone fractures were noted. All were open fractures with large, deep avulsion wounds. Displaced and comminuted fractures received reduction and fixation before wound closure. Three patients had cranial bone fracture with no displacement. Brain edema and subarachnoid hemorrhage were found by brain CT scan in two and one patients respectively. They were treated conservatively. In one patient with frontal sinus fracture the glass pieces penetrated into the brain. The foreign bodies were removed from the brain and frontal sinus. Eyeball rupture was found in 16 patients, including two patients in whom both eyes were involved. Eight eyeballs needed immediate evisceration and ten eyeballs received reparation. Blindness occurred in all these patients. Of the 99 patients in this study, 15% sustained additional injury. Most were wounds on the extremities. Because serious injuries can be caused by the old type of windshields, it should be abandoned. Driving with the seat belt fastened is the best way to insure safety. PMID- 8510199 TI - [Effective renal plasma flow in renal transplant rejection]. AB - It is important to differentiate between cell-mediated (acute) and humoral (chronic) rejection in renal transplantation in order to initiate appropriate therapy. Since effective renal plasma flow (ERPF) provides a sensitive method of analyzing renal function, this test was undertaken to evaluate the possibility of differentiating acute and chronic rejections by ERPF. A total of 90 patients (no rejection: 33, acute rejection: 45, chronic rejection: 12) were retrospectively included in this study. ERPF was determined by performing comprehensive renal function test (Tauxe et al., 1980) and Student's unpaired t-test was used to evaluate the statistical difference (no rejection vs chronic rejection, no rejection vs acute rejection, acute rejection vs chronic rejection). The ERPF value of the no rejection group (228.9 +/- 119.2 ml/min) was significantly higher than the ERPF value of the acute rejection group (167.5 +/- 86.9 ml/min) and the chronic rejection group (137.2 +/- 60.2 ml/min) (P < 0.05). By in contrast, there was no significant difference between the acute rejection group and the chronic rejection group (P > 0.05). We concluded that ERPF value alone could not differentiate between acute rejection and chronic rejection in renal transplantation. PMID- 8510200 TI - [Blunt small intestinal trauma]. AB - From 1986 to 1990, 41 patients with blunt small intestinal trauma were hospitalized and underwent surgery in Kuang Tien General Hospital. Included were 34 males and 7 females with a mean age of 37 years (range: 8 to 67). The mean duration of follow-up was 41 months. We classified the severity of small intestinal injury with the duodenum organ injury scale or small bowel organ injury scale published by the Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A. A. S. T.) in 1990. According to the operative findings, the small intestinal injuries of the 41 cases were classified as follows: grade I-11 cases, grade II-16 cases, grade III-8 cases, grade IV-2 cases, and grade V-7 cases. Three cases had both duodenal and small bowel injuries. Among the patients, 4 cases were treated by drainage. Seven cases underwent simple repair. Three cases were treated with repair and drainage. Thirteen cases underwent enterorrhaphy and drainage. Seventeen cases were treated with resection and anastomosis. The mortality rate was 7.2%, whilst the morbidity rate was 34.0%. The most frequent postoperative complications related to the small intestinal injury in patients who survived the initial operation were wound infection (22.0%), intra-abdominal abscesses (4.8%), pulmonary infection (4.8%), and small bowel obstruction (2.4%). PMID- 8510201 TI - Ovarian mucinous cystadenocarcinoma with mural nodules of anaplastic carcinoma: report of a case and review of the literature. AB - Cases of ovarian mucinous cystadenocarcinoma with mural nodules of anaplastic carcinoma are very rare. We report on such a case and review the literature. The mural nodules in our case were made up mainly of anaplastic spindle cells and numerous osteoclast-like giant cells. They resembled sarcoma or sarcoma-like mural nodules under light microscopy. The anaplastic cells within the nodules were immunopositive for both cytokeratin and vimentin, and ultrastructurally they displayed desmosomes. This case reaffirms the value of immunohistochemistry and ultrastructural study to establish the nature of such nodules, and the importance of making such distinctions. PMID- 8510202 TI - Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. AB - Apoptotic programmed cell death occurs when the insect cell line SF-21, derived from Spodoptera frugiperda, is infected with mutants of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) which lack a functional p35 gene. However, infection of the Trichoplusia ni TN-368 cell line with p35 mutants does not result in apoptosis (R. Clem, M. Fechheimer, and L. Miller, Science 254:1388-1390, 1991). We have examined the effect of apoptosis on AcMNPV infections in cell lines and larvae of these two insect species. Production of viral progeny was significantly lower in SF-21 cells infected with p35 mutants than in cells infected with wild-type (wt) or revertant viruses. Viral gene expression was abnormal in SF-21 cells infected with p35 mutants; there was a delay in the transcription and translation of early and late viral genes, a lack of expression of very late genes, and a total cessation of protein synthesis late in the apoptotic process. In vivo analysis revealed that the dose of budded virus required for 50% lethality in S. frugiperda larvae was approximately 1,000-fold higher for p35 mutants than for wt or revertant viruses. In contrast, the replication and infectivity of p35 mutant viruses was equivalent to that of wt AcMNPV during infection of both TN-368 cells and T. ni larvae. Thus, the data indicate that a host apoptotic response provides protection against viral infection at the organismal level and that the p35 gene constitutes a host range determinant for AcMNPV infection. PMID- 8510203 TI - The full-length Tat protein is required for TAR-independent, posttranscriptional trans activation of human immunodeficiency virus type 1 env gene expression. AB - Tat is a protein that dramatically increases the expression of all genes expressed from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat through interaction with a cis-acting target sequence referred to as TAR (for trans-acting responsive region). The tat gene is divided into two coding exons which, when translated, result in the synthesis of an 86-amino-acid protein. However, the 72-amino-acid segment encoded by the first coding exon of tat is sufficient to encode a fully active Tat protein in known assays. We examined expression of the env gene from an LTR that lacks TAR (designated dTAR env). Surprisingly, only the full-length Tat peptide trans activated expression of the env gene from dTAR-env. Comparison of RNA and protein expression of the env gene in the presence of Tat indicated that the mechanism of trans activation is posttranscriptional rather than transcriptional. To test whether the TAR independent Tat function is specific to the HIV-1 env gene, we analyzed expression of heterologous genes from the long terminal repeat lacking TAR. These heterologous genes were not trans activated by Tat in the absence of a TAR element, which suggests that the second-exon peptide of Tat has a sequence specific role in TAR-independent trans activation of the HIV-1 env gene. Analysis of a mutant in the 5' end of the env gene was used to identify a cis-acting sequence required for Tat responsiveness. PMID- 8510204 TI - Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis. AB - The capacities to induce the synthesis of hepatitis B virus (HBV) unit-length DNA were compared for two HBV DNAs with an overall sequence diversity of about 10%. They had been cloned from serum (DNA2) and from a hepatocellular carcinoma (DNA4), respectively. As a major difference, DNA4 carries a translational stop signal preventing the synthesis of precore protein. Progeny DNA yields obtained after transfection with respective pregenome transcription units allocated DNA2 to a low-replicator and DNA4 to a high-replicator phenotype. Cotransfection of DNA2 interfered with progeny DNA synthesis induced by DNA4. By mutual exchange of restriction fragments, the region on the viral genome responsible for the differing replicator phenotypes was confined to a sequence comprising the 3' terminal part of the X gene, core promoter, encapsidation signal epsilon, precore/core gene, and 5'-terminal part of the pol gene. Point mutations in DNA2 abolishing proper expression of the precore gene strongly enhanced the yield of progeny DNA, whereas cotransfection of a precore expression plasmid with DNA4 or with the mutated DNA2 substantially lowered the amount of progeny DNA. Hence, precore expression acts as an inhibitory principle for HBV replication. The same stop mutation as in DNA4 has been found to arise frequently in virus carriers. Loss of precore expression and concomitant conversion to a more severe hepatitis, as observed in the course of a chronic infection, thus can be explained by a relaxation of replication-level control. PMID- 8510205 TI - A direct demonstration of recombination between an injected virus and endogenous viral sequences, resulting in the generation of mink cell focus-inducing viruses in AKR mice. AB - We analyzed viral recombination events that occur during the preleukemic period in AKR mice. We tagged a molecular chimera between the nonleukemogenic virus Akv and the leukemogenic mink cell focus-inducing (MCF) virus MCF 247 with an amber suppressor tRNA gene, supF. We injected the supF-tagged chimeric virus that contains all of the genes of MCF 247 except the envelope gene, which in turn is derived from Akv, into newborn AKR mice to evaluate its pathogenic potential. Approximately the same percentage of animals developed leukemia with similar latent periods when injected with either the tagged or nontagged virus. DNA from tumors induced in AKR mice by the tagged chimeric virus was analyzed by Southern blotting with the supF gene as a probe. One set of tumors contained the injected supF-tagged virus. Two kinds of supF-tagged proviruses were found in a second set of tumors. One group of supF-tagged viruses had a restriction map consistent with that of the injected virus, while the other group of proviruses had restriction maps that suggested that the proviruses had acquired an MCF virus-like envelope gene by recombination with endogenous viral sequences. These results demonstrate that injected viruses recombine in vivo with endogenous viral sequences. Furthermore, the progression to leukemia was accelerated in mice that develop tumors containing proviruses with an MCF virus env gene, emphasizing the importance of the role of the MCF virus env gene product in transformation. PMID- 8510206 TI - In vitro transcription from baculovirus late gene promoters: accurate mRNA initiation by nuclear extracts prepared from infected Spodoptera frugiperda cells. AB - Extracts prepared from nuclei of Autographa californica nuclear polyhedrosis virus-infected Spodoptera frugiperda cells were shown to support in vitro transcription from baculovirus late gene promoters. In vitro transcription was optimized for the late promoter of the 39K gene. The Mg2+ concentration was critical; concentrations higher than 1 to 2 mM did not support late transcription. Additional conditions included template (40 micrograms/ml), extract (2.5 mg/ml), and incubation time (25 min). Using a combination of runoff assays and high-resolution primer extension analyses, this system was shown to accurately initiate transcription from a variety of baculovirus late gene promoters, including those from the 39K and p39/capsid late genes and the hyperexpressed p10 and polyhedrin very late genes. In vitro transcription from the 39K late promoter was resistant to high concentrations of both alpha-amanitin (100 micrograms/ml) and tagetitoxin (4,000 U/ml), suggesting that neither RNA polymerase II nor III is responsible for the transcription of baculovirus late genes. PMID- 8510207 TI - Physicochemical dissociation of CD4-mediated syncytium formation and shedding of human immunodeficiency virus type 1 gp120. AB - The mechanism of CD4-mediated fusion via activated human immunodeficiency virus type 1 (HIV-1) gp41 and the biological significance of soluble CD4 (sCD4)-induced shedding of gp120 are poorly understood. The purpose of these investigations was to determine whether shedding of gp120 led to fusion activation or inactivation. BJAB cells (TF228.1.16) stably expressing HIV-1 envelope glycoproteins (the gp120 gp41 complex) were used to examine the effects of pH and temperature on sCD4 induced shedding of gp120 and on cell-to-cell fusion (syncytium formation) with CD4+ SupT1 cells. sCD4-induced shedding of gp120 was maximal at pH 4.5 to 5.5 and did not occur at pH 8.5. At physiologic pH, sCD4-induced shedding of gp120 occurred at 22, 37, and 40 degrees C but neither at 16 nor 4 degrees C. In contrast, syncytia formed at pH 8.5 (maximally at pH 7.5) but not at pH 4.5 to 5.5. At pH 7.5, syncytia formed at 37 and 40 degrees C but not at 22, 16, or 4 degrees C. Preincubation of cocultures of TF228.1.16 and SupT1 cells at 4, 16, or 22 degrees C before the shift to 37 degrees C resulted in similar, increased, or decreased syncytium formation, respectively, compared with the control. Furthermore, an activated intermediate of CD4-gp120-gp41 ternary complex may form at 16 degrees C; this intermediate rapidly executes fusion upon a shift to 37 degrees C but readily decays upon a shift to the shedding-permissive but fusion nonpermissive temperature of 22 degrees C. These physicochemical data indicate that shedding of HIV-1 gp120 is not an integral step in the fusion cascade and that CD4 may inactivate the fusion complex in a process analogous to sCD4-induced shedding of gp120. PMID- 8510208 TI - Polygenic control of neuroinvasiveness in California serogroup bunyaviruses. AB - The pathogenesis of the California serogroup bunyaviruses includes both extraneural and intraneural replicative phases that can be separated experimentally. The present study dissects the viral genetic determinants of extraneural replication. We have previously described two attenuated reassortant clones of California serogroup bunyaviruses which exhibit reduced neuroinvasiveness after subcutaneous inoculation into suckling mice. Clone B1-1a bears an attenuated middle RNA segment (neuroinvasiveness phenotype v alpha v), and clone B.5 bears an attenuated large RNA segment (neuroinvasiveness phenotype alpha vv). We prepared reassortant viruses between these two strains and found that the two attenuated gene segments acted independently and additively, since reassortants bearing two attenuated RNA segments were more attenuated than the parental clones. Reassortants bearing no attenuated RNA segments were much more neuroinvasive than either parental clone, indicating that a neuroinvasive strain can be derived from two attenuated clones. Pathogenesis studies demonstrated that after injection of 10(3) PFU, the attenuated reassortant clones did not replicate in peripheral tissue, failed to reach the brain, and did not cause disease. At a dose of 10(6) PFU, attenuated clones failed to replicate to a significant level in peripheral tissue and produced only a minimal passive plasma viremia during the first 24 h but nevertheless reached high titers in the brain and killed mice. Because of this result, we investigated the possibility that neuroinvasion occurs via retrograde axonal transport, by determining whether sciatic nerve sectioning could protect against virus infection after hind leg footpad inoculation. We found that nerve sectioning had no effect on lethality, ruling out this mode of entry and suggesting that passive viremia is likely to be sufficient for invasion of the central nervous system. PMID- 8510209 TI - Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: the cytoplasmic domain of CD4 contributes to Vpu sensitivity. AB - CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus (HIV) receptor for infection of human host cells. We have recently demonstrated that Vpu, an HIV type 1 (HIV-1) encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. In this report, we describe an in vitro model system that allowed us to define important parameters for Vpu-dependent CD4 degradation. The rate of CD4 decay in rabbit reticulocyte lysate was approximately one-third of that observed previously in tissue culture experiments in the presence of Vpu (40 versus 12 min) and required no other HIV-1 encoded proteins. Degradation was contingent on the presence of microsomal membranes in the assay and the coexpression of Vpu and CD4 in the same membrane compartment. By using the in vitro degradation assay, the effects of specific mutations in CD4, including C-terminal truncations and glycosylation mutants, were analyzed. The results of these experiments indicate that Vpu has the capacity to induce degradation of glycosylated as well as nonglycosylated membrane-associated CD4. Truncation of 13 C-terminal amino acids of CD4 did not affect the ability of Vpu to induce its degradation. However, the removal of 32 amino acids from the C-terminus of CD4 completely abolished sensitivity to Vpu. This suggests that Vpu targets specific sequences in the cytoplasmic domain of CD4 to induce its degradation. We also analyzed the effects of mutations in Vpu on its biological activity in the in vitro CD4 degradation assay. The results of these experiments suggest that sequences critical for this function of Vpu are located in its hydrophilic C-terminal domain. PMID- 8510210 TI - Assembly of Theiler's virus recombinants used in mapping determinants of neurovirulence. AB - A major determinant of neurovirulence for the GDVII strain of Theiler's virus, a murine picornavirus, was mapped to the P1 capsid protein region. Chimeric viruses were constructed by using sequences from the 5' noncoding and P1 regions of the virulent GDVII strain to replace equivalent regions of the less virulent BeAn strain. Neurovirulence in mice progressively increased as larger regions of BeAn capsid protein-encoding sequences were replaced. The in vitro growth characteristics of the chimeras showed that some chimeras were growth delayed in BHK-21 cells even though the viral constructs exhibited larger plaque sizes, were less temperature sensitive, and were more thermally stable than BeAn. Examination of assembly intermediates revealed an altered pentamer conformation and delayed empty capsid formation for the growth-compromised viruses. For these constructs, their chimeric nature inadvertently resulted in virion assembly defects that complicated finer-scale mapping of the determinants of virulence within the capsid region. These results demonstrate the importance of determining in vitro growth characteristics of chimeras to correctly decipher the significance of their phenotypes. VP1 does not contain a complete determinate for virulence because a chimera with VP1-encoding sequences from GDVII in an otherwise BeAn virus has an attenuated phenotype but is not growth compromised in vitro. The source of sequences, BeAn or GDVII, in the 5' noncoding region had only slight effects on the virulence of recombinant constructs. PMID- 8510211 TI - The NFIII/OCT-1 binding site stimulates adenovirus DNA replication in vivo and is functionally redundant with adjacent sequences. AB - The inverted terminal repeat (ITR) of adenovirus type 5 (Ad5) is 103 bp in length and contains the origin of DNA replication. Cellular transcription factors NFI/CTF and NFIII/OCT-1 bind to sites within the ITR and participate in the initiation of viral DNA replication in vitro. The ITR also contains multiple copies of two conserved sequence motifs that bind the cellular transcription factors SP1 and ATF. We have analyzed a series of viruses that carry deletions at the left terminus of Ad5. A virus carrying a deletion of the NFIII/OCT-1, SP1, and ATF sites within the ITR (mutant dl309-44/107) was wild type for virus growth. However, the deletion of these elements in addition to sequences immediately flanking the ITR (mutant dl309-44/195) resulted in a virus that grew poorly. The analysis of growth parameters of these and other mutants demonstrate that the NFIII/OCT-1 and adjacent SP1 sites augment the accumulation of viral DNA following infection. The function of these elements was most evident in coinfections with a wild-type virus, suggesting that these sites enhance the ability of a limiting trans-acting factor(s), that stimulates viral DNA replication, to interact with the ITR. The results of these analyses indicate functional redundancy between different transcription elements at the left terminus of the Ad5 genome and demonstrate that the NFIII/OCT-1 site and adjacent SP1 site, previously thought to be nonessential for adenovirus growth, play a role in viral DNA replication in vivo. PMID- 8510212 TI - Independent variation and positive selection in env V1 and V2 domains within maternal-infant strains of human immunodeficiency virus type 1 in vivo. AB - Multiple targets for immune recognition and cellular tropism are localized to the V1 and V2 hypervariable regions in the amino portion of human immunodeficiency virus type 1 (HIV-1) gp120env. We have assessed genetic diversity in env V1 and V2 hypervariable domains in vivo within epidemiologically related strains of HIV 1. Our strategy was to analyze longitudinal samples from two seropositive mothers and multiple children infected by perinatal transmission. Although the V1 and V2 domains are closely linked in the HIV-1 genome, nucleotide sequences in V1 and in V2 evolved independently in maternal-infant viruses in vivo. A high proportion of the nucleotide substitutions would introduce amino acid diversity in V1 and in V2. A significant excess of nonsynonymous over synonymous substitutions was identified in HIV-1 env V1 and V2 peptides in the mothers and in two older children but was not generally apparent in HIV-1 sequences in infants. An excess of nonsynonymous over synonymous substitutions indicated that there is positive selection for independent genetic variation in the V1 and V2 domains in vivo. It is likely that there are host responses to complex determinants in the V1 or V2 hypervariable domain of HIV-1 gp120. PMID- 8510213 TI - Packaging of human immunodeficiency virus type 1 RNA requires cis-acting sequences outside the 5' leader region. AB - cis elements required for the encapsidation of human immunodeficiency virus type 1 (HIV-1) RNA have been investigated by using a replication-competent helper virus to package a series of HIV-1-based vectors which had been stably transfected into human CD4 T-cell lines. A previously identified packaging signal in the 5' leader region was not sufficient for the encapsidation of small vectors containing heterologous genes. In contrast, vectors containing additional gag and env sequences were packaged with high efficiency and transduced into CD4 expressing target cells with titers exceeding 10(4) CFU/ml. The presence of gag sequences did not enhance vector packaging efficiency. A 1.1-kb env gene fragment encompassing the Rev-responsive element was absolutely required for the expression and encapsidation of vectors containing cis-acting repressive sequences and appeared also to contain an important packaging signal. Vectors as small as 2.6 kb were successfully packaged in this system. The presence of abundant, packageable vector RNA did not appear to interfere with encapsidation of the wild-type HIV-1 genome, suggesting that HIV-1 RNA packaging capacity is not saturated during acute infection. PMID- 8510214 TI - The two zinc fingers in the human immunodeficiency virus type 1 nucleocapsid protein are not functionally equivalent. AB - The highly conserved zinc fingers in retroviral nucleocapsid (NC) proteins have the general structure Cys-(X)2-Cys-(X)4-His-(X)4-Cys. Human immunodeficiency virus type 1 (HIV-1) contains two Zn2+ fingers, and mutants were constructed in which the native sequence of each Zn2+ finger was maintained but their positions in the NC protein were changed. Mutants had either two first-finger sequences (pNC1/1), two second-finger sequences (pNC2/2), or reversed first- and second finger sequences (pNC2/1). Cells transfected with mutant or wild-type clones produced similar levels of Tat, Gag, Pol, and Env proteins, formed syncytia, and shed viruslike particles that were indistinguishable by electron microscopy. However, the pNC2/1 and pNC2/2 mutants were inefficient in packaging genomic RNA (less than 15% of wild-type levels), whereas the pNC1/1 mutant packaged approximately 70% of wild-type levels of RNA. No infectious virus could be detected with either the pNC2/1 or pNC2/2 mutants, whereas the pNC1/1 mutant appeared to sustain a low level of replication and reverted to a competent wild type-like viral species after a 2- to 4-week lag period. The data strongly suggest that the two Zn2+ fingers of HIV-1 are not functionally equivalent and that the first Zn2+ finger in the Gag precursor plays a more prominent role in RNA selection and packaging. The data also indicate that both Zn2+ fingers in the mature NC protein play as yet unknown roles in viral assembly or the early stages of the viral infection process. PMID- 8510215 TI - Partial inhibition of the human immunodeficiency virus type 1 protease results in aberrant virus assembly and the formation of noninfectious particles. AB - The production of infectious particles by human immunodeficiency virus type 1 is dependent on the accurate cleavage of its Gag and Gag/Pol precursors by a virally encoded protease. In the absence of protease activity, morphologically abnormal particles which are noninfectious are formed. Recently, inhibitors of the protease of human immunodeficiency virus type 1 have been developed as potential therapeutic agents. We have examined the basis for the loss of infectivity at the limiting inhibitor concentrations that are likely to be achieved in clinical settings. We found that subtle defects in processing are correlated with profound deficits in infectivity. Further, we correlated this partially disrupted processing with an altered virion morphology. These data suggest that accurate and complete processing is essential to the formation of infectious, morphologically normal virions and that the pathway by which these precursors are processed and assembled is sensitive to partial inhibition of the protease by an inhibitor disproportionate to the effect of the inhibitor on the viral protease itself. PMID- 8510216 TI - Characterization of a naturally occurring ecotropic receptor that does not facilitate entry of all ecotropic murine retroviruses. AB - A fibroblast cell line (MDTF) derived from the feral mouse Mus dunni is resistant to infection by Moloney murine leukemia virus (Mo-MuLV), an ecotropic murine leukemia virus (E-MuLV) (M. R. Lander and S. K. Chattopadadhyay, J. Virol. 52:695 698, 1984). MDTF cells can be infected by other E-MuLVs such as Friend MuLV and Rauscher MuLV, which have been demonstrated to use the same receptor as Mo-MuLV in NIH 3T3 cells (A. Rein and A. Schultz, Virology 136:144-152, 1984). We have now shown that the block to Mo-MuLV infection of MDTF cells occurs at the level of the envelope-receptor interaction. We have cloned the ecotropic receptor cDNA from MDTF cells (dRec) and compared its sequence with that of the NIH 3T3 cell receptor (mRec). Although the deduced dRec and mRec proteins differ at only four amino acid residues, we demonstrate that these changes account for the resistance of MDTF cells to Mo-MuLV infection. Our findings suggest that retroviruses in the same receptor class can exhibit different host ranges due to single amino acid differences in their cellular receptor. PMID- 8510217 TI - Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells. AB - Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating antigens is difficult to achieve. Exogenous antigens, such as viral proteins and peptides, normally induce CD4+ T-cell responses unless appropriately delivered to the major histocompatibility complex class I antigen presentation pathway. In vitro studies performed to address this issue revealed a similar scenario, and primary CTL induction with nonreplicating antigens has rarely been reported. This study demonstrated primary antiviral CTL induction in vitro with exogenous antigens delivered in vivo to dendritic cells. This study also evaluated the efficacy of glycoprotein B peptide (free or encapsulated in liposomes), peptide-tripalmitoyl S-glyceryl cysteinyl conjugate (acylpeptide), and glycoprotein B protein encapsulated in pH-sensitive liposomes as antigen delivery vehicles. Our results show that higher levels of cytotoxicity against herpes simplex virus type 1 resulted from exposure of dendritic cells to peptide-tripalmitoyl-S-glyceryl cysteinyl in liposomes. Macrophages treated in a similar manner were not effective stimulators for primary CTL induction. Our data have relevance to the understanding of mechanisms of antigen processing and presentation and the design of antiviral vaccines. PMID- 8510218 TI - Simian immunodeficiency virus mutants resistant to serum neutralization arise during persistent infection of rhesus monkeys. AB - We previously described the pattern of sequence variation in gp120 following persistent infection of rhesus monkeys with the pathogenic simian immunodeficiency virus SIVmac239 molecular clone (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843, 1991). Sequence changes were confined largely to five variable regions (V1 to V5), four of which correspond to human immunodeficiency virus type 1 (HIV-1) gp120 variable regions. Remarkably, 182 of 186 nucleotide substitutions that were documented in these variable regions resulted in amino acid changes. This is an extremely nonrandom pattern, which suggests selective pressure driving amino acid changes in discrete variable domains. In the present study, we investigated whether neutralizing-antibody responses are one selective force responsible at least in part for the observed pattern of sequence variation. Variant env sequences called 1-12 and 8-22 obtained 69 and 93 weeks after infection of a rhesus monkey with cloned SIVmac239 were recombined into the parental SIVmac239 genome, and variant viruses were generated by transfection of cultured cells with cloned DNA. The 1-12 and 8-22 recombinants differ from the parental SIVmac239 at 18 amino acid positions in gp120 and at 5 and 10 amino acid positions, respectively, in gp41. Sequential sera from the monkey infected with cloned SIVmac239 from which the 1-12 and 8-22 variants were isolated showed much higher neutralizing antibody titers to cloned SIVmac239 than to the cloned 1-12 and 8-22 variants. For example, at 55 weeks postinfection the neutralizing antibody titer against SIVmac239 was 640 while those to the variant viruses were 40 and less than 20. Two other rhesus monkeys infected with cloned SIVmac239 showed a similar pattern. Rhesus monkeys were also experimentally infected with the cloned variants so that the type-specific nature of the neutralizing antibody responses could be verified. Indeed, each of these monkeys showed neutralizing-antibody responses of much higher titer to the homologous variant used for infection. These experiments unambiguously demonstrate that SIV mutants resistant to serum neutralization arise during the course of persistent infection of rhesus monkeys. PMID- 8510219 TI - Transgenic Fv-4 mice resistant to Friend virus. AB - Fv-4 is a mouse gene that confers resistance to infection with ecotropic retroviruses. A candidate Fv-4 gene was cloned previously and found to resemble the 3' half of a murine leukemia virus (MuLV). To study the effect of this gene in vivo, we generated two transgenic mouse strains carrying the Fv-4 env gene under control of its presumed natural promoter, a cellular sequence unrelated to retroviruses. Transgenic progeny expressed a 3-kb Fv-4 env RNA in all of the organs and tissues examined, as well as an Fv-4 envelope antigen on the surface of thymocytes and spleen cells, similar to mice carrying the natural Fv-4 gene. One of the two transgenic strains (designated Fv4-2) expressed three to nine times as much transgene RNA and protein as the other strain (Fv4-11). When challenged with a Friend virus complex containing up to 10(4) XC PFU of Friend MuLV, Fv4-2 mice were completely resistant to development of splenomegaly and had no detectable ecotropic virus in the spleen or blood, confirming that the cloned Fv-4 gene is responsible for resistance to ecotropic MuLV in vivo. In contrast, Fv4-11 mice were only partially resistant, developing viremia and splenomegaly at the highest inoculum dose but recovering from viremia several weeks after inoculation with 10-fold less virus. The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response. PMID- 8510220 TI - Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein independent function. AB - Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed from the same, singly spliced message as the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous studies suggest that Vpu functions in the late stages of viral replication, possibly in virus egression from the cell. Recently, it has been demonstrated that Vpu functions to allow gp160 to be more efficiently processed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression. This reduction persists when HIV-1 particles are pseudotyped with the HIV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse-chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 and envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelope glycoprotein expression. PMID- 8510221 TI - Repression of RNA polymerase III transcription by adenovirus E1A. AB - Adenovirus E1A encodes two major proteins of 289 and 243 amino acids (289R and 243R), which both have transcription regulatory properties. E1A-289R is a transactivator whereas E1A-243R primarily functions as a repressor of transcription. Here we show that E1A repression is not restricted to RNA polymerase II genes but also includes the adenovirus virus-associated (VA) RNA genes. These genes are transcribed by RNA polymerase III and have previously been suggested to be the target of an E1A-289R-mediated transactivation. Surprisingly, we found that during transient transfection both E1A proteins repressed VA RNA transcription. E1A repression of VA RNA transcription required both conserved regions 1 and 2 and therefore differed from the E1A-mediated inhibition of simian virus 40 enhancer activity which primarily required conserved region 1. The repression was counteracted by the E1B-19K protein, which also, in the absence of E1A, enhanced the accumulation of VA RNA. Importantly, we show that efficient VA RNA transcription requires expression of both E1A and the E1B-19K protein during virus infection. PMID- 8510222 TI - Differential expression of Rel family members in human T-cell leukemia virus type I-infected cells: transcriptional activation of c-rel by Tax protein. AB - The Tax protein of the human T-cell leukemia virus type I (HTLV-I) has been shown to induce nuclear expression of Rel family NF-kappa B-binding proteins. However, under different experimental conditions, different J. H. Kim, Y. Daitoku, and W. G. Greene, J. Virol. 65:6892-6899, 1991). In this study, using specific immunological reagents capable of distinguishing individual members of the Rel family proteins, we show that only c-Rel, not NF-kappa B p50 or p65, is induced in HTLV-I-infected cells. Preferential c-rel induction by HTLV-I infection was detected at the protein and RNA levels as well as in the nuclear NF-kappa B binding form. Induced c-rel expression was also detected in cells stably transfected with tax cDNA, further correlating the c-rel induction with viral Tax expression. An increase in c-rel mRNA was detected within 3 h after induction of Tax expression, suggesting that this effect is at least partially regulated at the level of transcription. Furthermore, using a particle bombardment method for gene cotransfection, we show that Tax can transcriptionally activate the c-rel promoter in a T-cell line, Jurkat. PMID- 8510223 TI - Genomic organization and expression of Tpl-2 in normal cells and Moloney murine leukemia virus-induced rat T-cell lymphomas: activation by provirus insertion. AB - Tpl-2 is a gene encoding a protein kinase which is primarily expressed in normal spleen, thymus, and lung tissue and is activated by provirus insertion in Moloney murine leukemia virus-induced T-cell lymphomas during the late stages of oncogenesis. Tpl-2 is composed of eight exons and spans a 35-kb genomic DNA region. The provirus integrates reproducibly in the last intron and in the same transcriptional orientation as the Tpl-2 gene. This genetic change leads to the expression of enhanced steady-state levels of a truncated Tpl-2 RNA transcript which is predicted to encode a protein with an altered C-terminal domain. Tpl-2 is transcribed from two alternating promoters, P1 and P2. The RNA transcripts originating in the two promoters harbor different 5' untranslated regions derived from the alternate noncoding exons IA and IB. Utilization of the P2 promoter, which gives rise to exon IB containing Tpl-2 RNA transcripts, was detected primarily in tumor cells. The Tpl-2 protein was expressed in COS-1 cells as an N terminal fusion with a 12-amino-acid hemagglutinin tag. Immunoprecipitation of transfected COS-1 cell lysates with antihemagglutinin or anti-Tpl-2 antibodies, followed by incubation with [gamma-32P]ATP, confirmed that Tpl-2 possesses protein kinase activity. PMID- 8510224 TI - An intramolecular disulfide bridge between Cys-7 and Cys61 determines the structure of the secretory core gene product (e antigen) of hepatitis B virus. AB - Hepatitis B virus, the prototypic member of the Hepadnaviridae, is a small enveloped DNA virus that replicates via reverse transcription. Efficient usage of its compact 3.2-kb genome is exemplified by the pre-C/C gene from which two proteins with largely overlapping primary sequences but distinctly different properties are synthesized: the self-assembling core protein p21c (hepatitis B core antigen [HbcAg]) and the secretory, nonparticulate protein p17e (hepatitis B e antigen [HbeAg]). Mature p17e carries a 10-amino-acid N-terminal extension with a Cys residue (Cys-7). Using transient transfection of a human liver cell line with constructs expressing wild-type p17 or a series of Cys mutants of p17, we show that Cys-7 forms an intramolecular S-S bond to Cys61, which in assembly competent core proteins is available for intermolecular disulfide bonds between two neighboring subunits. Removal of the Cys-7/Cys61 bond by mutating either residue has differential effects: in the absence of Cys-7, secretion is relatively efficient and independent of Cys61; however, the molecules are exported as homodimers exhibiting both HBe and HBc antigenicity. In the absence of Cys61, the nonpaired Cys-7 interferes with secretion efficiency. The amino acid sequence flanking Cys-7 also contributes to the formation of the proper intramolecular S-S bond. These results suggest that the Cys-7/Cys61 bond imposes on p17e a conformation that is critical for its secretion and distinct biophysical and antigenic properties. This mechanism adds selective disulfide formation to the repertoire of hepatitis B virus for efficient use of its tiny genome. PMID- 8510225 TI - Hepatitis B virus (HBV) binding factor in human serum: candidate for a soluble form of hepatocyte HBV receptor. AB - A hepatitis B virus (HBV) binding factor (HBV-BF) was identified in normal human serum interacting with the pre-S1 and pre-S2 epitopes of the viral envelope located within the protein domains involved in recognition of hepatocyte receptor(s). This molecule was characterized as a 50-kDa glycoprotein showing an isoelectric point of 7.13 with a biological activity depending on its native molecular conformation and on intact sulfhydryl bonds. Monoclonal antibodies to HBV-BF recognized a membrane component of the normal human liver whereas they were unreactive with hepatocyte membranes of other species and with those of the HepG2 cell line. These results suggest that the HBV-BF represents a soluble fragment of the membrane component and can be related to the HBV receptor mediating attachment of HBV to human liver cells. PMID- 8510226 TI - Vaccination to prevent persistent viral infection. AB - Persistent virus infections are increasingly being recognized as a significant cause of human morbidity and mortality. To establish persistence, a virus must establish infection and evade eradication by the host immune response, in particular by cytotoxic T lymphocytes (CTL). We have studied a virus that establishes persistence in part by suppressing the CTL response of the infected host. The virus persists in many cell types, including lymphocytes and macrophages. We show that prior immunization with a vaccine designed to induce CTL (in the absence of antiviral antibody) confers complete protection against subsequent establishment of persistence in all tissues analyzed. The vaccine can be designed to express as few as 10 amino acids of a viral protein that comprise the CTL epitope. Further, two CTL epitopes for two discrete MHC haplotypes can be successfully used in a single vaccine that protects both strains of mice. Hence, a "string of CTL epitopes" (beads) concept for vaccination is feasible. Finally, the CTL vaccine provided protection against the establishment of persistence by an immunosuppressive virus. PMID- 8510227 TI - Vpx of simian immunodeficiency virus is localized primarily outside the virus core in mature virions. AB - Human immunodeficiency virus type 2 and the related simian immunodeficiency virus (SIV) contain a unique regulatory gene, vpx. The Vpx protein is packaged in mature virions and is required for efficient viral replication in peripheral blood lymphocytes and macrophages. To study the localization of Vpx in mature virions, conical and bar-shaped core structures of SIV from macaques (SIVmac) were purified. The SIVmac core has a density of approximately 1.25 g/cm3, compared with 1.16 g/cm3 for an intact virion. The relative proportions of major capsid protein (p27) and reverse transcriptase activity were similar for intact virions and core structures. The majority of matrix protein (p14) was removed from the purified core structure, suggesting its association with the viral membrane. Similarly, most of the Vpx protein was absent from the purified core structure. This result suggests that as with the matrix protein, the majority of Vpx proteins are localized outside the virus core. The localization of Vpx suggests that it may be involved in virus entry such as penetration or uncoating. PMID- 8510228 TI - Chimeric cDNA studies of Theiler's murine encephalomyelitis virus neurovirulence. AB - Strain GDVII and other members of the GDVII subgroup of Theiler's murine encephalomyelitis virus are highly neurovirulent and rapidly fatal, while strain DA and other members of the TO subgroup produce a chronic, demyelinating disease. GDVII/DA chimeric cDNA studies suggest that a major neurovirulence determinant is within the GDVII 1B through 1D capsid protein coding region, although the additional presence of upstream GDVII sequences, including the 5' untranslated region, contributes to full neurovirulence. Our studies indicate that there are limitations in precisely delineating neurovirulence determinants with chimeric cDNAs between evolutionarily diverged viruses, such as GDVII and DA. PMID- 8510229 TI - Antisense phosphorothioate oligodeoxynucleotides targeted to the vpr gene inhibit human immunodeficiency virus type 1 replication in primary human macrophages. AB - The replication of human immunodeficiency viruses (HIV) in human macrophages is influenced by genetic determinants which have been mapped predominantly to the viral envelope. However, in HIV-2, the vpr gene has also been suggested as an important modulator of viral expression in human macrophages. We synthesized five antisense phosphorothioate oligodeoxynucleotides complementary to the vpr mRNA of HIV-1Ba-L, a highly macrophage-tropic viral strain, and measured their effect on HIV-1Ba-L replication in primary human macrophages. All of the oligodeoxynucleotides displayed some level of non-sequence-specific inhibition of viral replication; however, only the antisense one had an additional effect on viral production in primary macrophages. Of the five antisense oligodeoxynucleotides tested, only one did not show any additional effect on viral production, whereas all the others inhibited viral replication to a similar degree (70 to 100%). Variation in the degree of inhibition was observed by using five different donors of human primary macrophages. The phosphorothioate oligonucleotides, targeted to the initiating methionine of the Vpr protein, had an inhibitory effect at both 20 and 10 microM only when the size was increased from 24 to 27 bases. Thus, HIV-1 replication in human macrophages is modulated by the expression of the vpr gene, and it is conceivable that vpr antisense oligodeoxynucleotides could be used in combination with antisense oligodeoxynucleotides against other HIV-1 regulatory genes to better control viral expression in human macrophages. PMID- 8510230 TI - Phorbol esters modulate the phosphorylation of human T-cell leukemia virus type I Tax. AB - The Tax protein from human T-cell leukemia virus type I (HTLV-I) is a 40-kDa phosphoprotein capable of activating transcription from its own long terminal repeat (LTR), as well as increasing the transcription of cellular genes. Transcriptional activation of the HTLV-I LTR has been demonstrated via a cyclic AMP-responsive element within the 21-bp Tax-responsive elements of the LTR. Phorbol esters also upregulate expression via the LTR. Since phosphorylation of Tax may play a role in these processes, we investigated the relative effects of kinase-stimulating agents on 32P incorporation into Tax. Our studies demonstrated that the phorbol ester 4 beta-phorbol-12 beta-myristate-13 alpha-acetate greatly stimulated Tax phosphorylation in a time- and dose-dependent manner. In contrast, 8-bromoadenosine 3'-5'-cyclic monophosphate induced little stimulation of Tax phosphorylation. Tax phosphorylation occurred only on serine residues and was mapped to a single tryptic fragment in both Tax-producing human lymphocytes and mouse fibroblast cells. PMID- 8510232 TI - Use of fluorescent in situ hybridization for deoxyribonucleic acid ploidy analysis of prostatic adenocarcinoma. AB - Fluorescent in situ hybridization using 2 chromosome specific centromere probes was evaluated as a method of ploidy analysis in touch preparations from 50 radical prostatectomy specimens. Tumors were classified as aneuploid by fluorescent in situ hybridization when nuclei had an abnormal copy number (aneusomic) for either chromosome centromere 8 or 12. Tetraploid tumors were defined as those with 4 copies (tetrasomic) of chromosome centromeres 8 and 12. The fluorescent in situ hybridization ploidy patterns were compared to the deoxyribonucleic acid (DNA) ploidy patterns subsequently obtained by flow cytometry on the same tissue following paraffin embedding. Concordant fluorescent in situ hybridization and flow cytometry ploidy classification was obtained in 82% of the cases (p < or = 0.0001). Of 7 aneuploid tumors 3 were identified by both methods. Trisomy 8 was detected by fluorescent in situ hybridization in 3 cases that were classified as DNA diploid (2 tumors) and DNA tetraploid (1 tumor). Conversely, flow cytometry detected aneuploidy (hypotetraploidy) in 1 tumor when the fluorescent in situ hybridization results were consistent with tetraploidy. Overall, fluorescent in situ hybridization was more sensitive in aneuploidy detection (6 of 7 cases) than flow cytometry (4 of 7). Of 19 tetraploid cases 5 had discordant fluorescent in situ hybridization and flow cytometry results. However, all 5 cases contained low levels of tetraploidy and the discrepant results were most likely due to the limits of precision of 1 or both methods. In conclusion, we demonstrated that fluorescent in situ hybridization ploidy analysis can be rapidly performed on fresh touch preparations of prostate tissue. This preliminary study demonstrates that the ploidy result determined by fluorescent in situ hybridization correlates well with that obtained by flow cytometry. More complete fluorescent in situ hybridization studies of prostate carcinoma will require additional probes for other chromosomes. PMID- 8510231 TI - Differential regulation of the human immunodeficiency virus type 2 enhancer in monocytes at various stages of differentiation. AB - We have demonstrated that stimulation of the human immunodeficiency virus type 2 (HIV-2) enhancer in T cells is dependent upon at least four cis-acting elements, including two purine-rich binding sites, PuB1 and PuB2, which are capable of binding members of the ets family of proto-oncogenes, the pets (peri-ets) site, which lies just upstream of the PuB2 site, and a single kappa B site (D. M. Markovitz, M. Smith, J. M. Hilfinger, M. C. Hannibal, B. Petryniak, and G. J. Nabel, J. Virol. 66:5479-5484, 1992). In this study, we examined the regulation of the HIV-2 enhancer in cells of monocytic lineage. We found that in immature monocytic cell lines, the HIV-2 enhancer is markedly induced by phorbol esters and that all four cis-acting elements are required for activation. In mature monocytic cells, constitutive activity is high, with only modest stimulation following phorbol ester treatment. Mutation of any of the four cis-acting elements resulted in greatly reduced basal expression in mature monocytes. This is in contrast to HIV-1, in which developmentally controlled expression of the enhancer in monocytes is mediated largely through the kappa B sites alone [G. E. Griffin, K. Leung, T. M. Folks, S. Kunkel, and G. J. Nabel, Nature (London) 339:70-73, 1989]. Further, we demonstrated that although both Elf-1, an ets family member with significant similarity to the drosophila developmental regulatory protein E74, and Pu.1, a monocyte- and B-cell-specific member of the ets family, bind the purine-rich enhancer region, Elf-1 is the protein which binds predominantly in vivo. A nuclear factor(s) which binds the pets site, an element which has been described only in HIV-2, was detected in extracts of all of the monocytic cells tested. These findings indicate that the mechanism by which cellular factors regulate HIV-2 enhancer function in monocytic cells differs significantly from that of HIV-1 and may offer a partial explanation for the differences in the biological and clinical characteristics of the two viruses. PMID- 8510233 TI - Intraoperative ultrasound in the evaluation of tumor involvement of the inferior vena cava. AB - The successful excision of genitourinary malignancies extending to the inferior vena cava relies heavily on accurate preoperative imaging. For the majority of these patients magnetic resonance imaging, inferior venacavography, abdominal ultrasound or abdominal computerized tomography will reliably predict the extent of inferior vena caval involvement by tumor. However, occasionally the results of these studies will conflict or be called into question intraoperatively. We report on 8 patients considered to be at risk for inferior vena caval involvement by tumor and for whom intraoperative ultrasound was obtained to clarify the presence or extent of thrombus. Five patients had renal cell carcinoma and 3 had adrenal carcinoma. In all patients concern as to the extent or presence of tumor was based on either inconclusive preoperative studies or unexpected intraoperative findings. In each case intraoperative ultrasound clearly visualized the inferior vena cava and established the presence or extent of tumor invasion. In 4 patients venacavotomy was avoided as a consequence of these findings. Intraoperative ultrasound is a useful tool that can accurately assess the inferior vena cava for possible tumor invasion, especially when the presence or extent of tumor involvement is not definitively established preoperatively. PMID- 8510235 TI - A simple method for the removal of indwelling ureteral stents in women. AB - A new method for transurethral removal of an indwelling ureteral stent has been developed. The 8-inch instrument has a thread-like element at an acting end, which forms a loop that is used to snare and extract the stent from the bladder. This device does not require endoscopic methods, is safe and easy to learn, and requires no specific equipment or facilities. PMID- 8510234 TI - Influence of wide excision of the neurovascular bundle(s) on prognosis in men with clinically localized prostate cancer with established capsular penetration. AB - We analyzed 107 men with clinically localized prostate cancer who had pathologically established capsular penetration in the region of the neurovascular bundles to determine the effect of wide excision of the neurovascular bundle(s) on disease-free survival. In 38 patients established capsular penetration was not suspected clinically and the neurovascular bundle(s) were preserved. In 69 patients established capsular penetration was suspected, and 1 or both neurovascular bundles were excised widely with the prostate. Disease-free survival was defined by an undetectable serum prostate specific antigen (PSA) level postoperatively. Wide excision of the neurovascular bundle(s) resulted in negative surgical margins in 40 of 69 patients (58%) compared to only 17 of 38 (45%) in whom the neurovascular bundle(s) was left intact (p = 0.03). Median interval to disease recurrence, as defined by a measurable serum PSA level, was 22 months in the group in whom the neurovascular bundles were preserved versus 33 months in the group undergoing wide excision (p = 0.03). At 39 months, however, 70% of the patients in both groups had detectable PSA levels. Similarly, patients with positive surgical margins had a mean interval to recurrence of 17 months compared to 38 months for the group with negative surgical margins (p = 0.0004). By 43 months, however, 75% of the patients in both groups had a detectable PSA level and the Kaplan-Meier curves had converged. Although wide excision of the neurovascular bundle(s) resulted in negative surgical margins more often with resultant delayed disease progression, most patients with established capsular penetration ultimately failed radical prostatectomy despite wide excision of periprostatic soft tissue. It seems likely, therefore, that many of these patients have occult metastatic disease at operation. Thus, recent enthusiasm for radical prostatectomy in men with locally advanced prostate cancer may not be justified. PMID- 8510236 TI - Characteristics and use of the in situ appendix as a continent catheterization stoma for continent urinary diversion in adults. AB - Use of the in situ appendix to provide continence was evaluated in 21 adults undergoing continent urinary diversion. The appendix with minimal or no manipulation was used in 20 of the 21 adults to provide the continence mechanism. Our findings indicate that in the majority of adults with no prior appendectomy the unaltered or minimally altered appendix is suitable to provide continence, and that dilating a narrow appendix is safe, effective and compatible with providing an adequate continence mechanism. PMID- 8510237 TI - Infantile hypertrophic pyloric stenosis and hydronephrosis: is there an association? AB - Infantile hypertrophic pyloric stenosis is a common condition requiring surgical intervention during the first few weeks of life. The incidence of infantile hypertrophic pyloric stenosis ranges from 0.13 to 0.4% of live births in the United States, Britain and Scandinavia. Associated anomalies have been described in 6 to 33% of the cases in the central nervous system, gastrointestinal tract and heart. An association of infantile hypertrophic pyloric stenosis with urinary tract anomalies has not been previously documented. A review of 422 patients with infantile hypertrophic pyloric stenosis revealed urinary tract anomalies in 6 (10 renal units), including 4 renal units with vesicoureteral reflux and 9 with hydronephrosis. This incidence of 1.4% is greater than the 0.2% incidence expected in the general population. This 7-fold increase in urinary tract anomalies in patients with infantile hypertrophic pyloric stenosis suggests an association between the two and warrants further investigation. Serious consideration should be given to obtaining renal ultrasound examinations in patients with infantile hypertrophic pyloric stenosis. PMID- 8510238 TI - The cephalotrigonal reimplant in bladder neck reconstruction for patients with exstrophy or epispadias. AB - A modified technique of ureteroneocystostomy with bladder neck plasty was used in 36 of 75 patients undergoing staged repair of bladder exstrophy or epispadias between 1986 and 1992. This procedure entails mobilizing the ureter while preserving the trigonal hiatus as with the cross-trigonal technique. The distal ureteral segments are directed superiorly toward the bladder dome rather than across the mid line. Of 75 patients 36 underwent cephalotrigonal reimplantation and 39 had a conventional cross-trigonal reimplant. Continence rate was 77% in the patients who underwent cephalotrigonal reimplantation and 72% in those who had a cross-trigonal reimplant. No patient had ureteral obstruction or vesicoureteral reflux. The ureter in exstrophy patients enters the bladder from an inferior position within the true pelvis. Directing the ureter superiorly rather than across the mid line provides a more gradual course through the hiatus and submucosal tunnel. The cranial course of the distal ureter frees more of the trigone for use in the rolled segment of the bladder neck and provides more muscle area for the tube. This is especially important in the patient in whom the distance between the mid prostate and trigone is particularly short. PMID- 8510239 TI - Valve of Guerin as a cause of dysuria and hematuria in young boys: presentation and difficulties in diagnosis. AB - A valve of Guerin, or lacuna magna, is a common anatomical finding in young boys. It occasionally causes dysuria and/or bloody urethral discharge or spotting due to its location distal to the external urethral sphincter. We report on 10 patients who underwent transmeatal marsupialization of a valve of Guerin between 1984 and 1991, and review the embryology and clinical presentation. Despite evidence suggesting that a valve of Guerin is a frequent, normal anatomical variant, the incidence of clinical detection is extremely low. While many patients with this condition remain totally asymptomatic, a valve of Guerin should be suspected in boys presenting with bleeding distal to the urethral sphincter with or without voiding symptoms. In most cases physical examination is normal. A carefully performed voiding cystourethrogram visualizing the distal urethra, coupled with endoscopic examination and gentle probing of the fossa navicularis, optimizes the likelihood of correct diagnosis. Treatment is indicated solely to ameliorate symptoms, which are probably caused by distention of the lacuna magna during voiding. Transmeatal incision and marsupialization of the valve leaflet into the urethral lumen usually effectively relieve dysuria and stop the bleeding. PMID- 8510240 TI - Leak point of incontinence: a measure of the interaction between outlet resistance and bladder capacity. AB - A total of 48 consecutive spina bifida patients undergoing routine urodynamic studies was classified into 2 groups depending upon whether they demonstrated uninhibited bladder contractions. Of the patients 34 demonstrated detrusor hyperreflexia and 14 had detrusor areflexia. These 2 groups were then subdivided depending on the continence status. Of the areflexic and hyperreflexic groups, 6 and 7 patients, respectively, were wet despite at least 2 years of conservative medical management. Leak point pressure and leak point volume were determined in all patients and results were compared in both subgroups. In the hyperreflexic groups leak point volume but not leak point pressure was significantly different between the wet and dry patients. The areflexic group demonstrated the opposite finding, that is the leak point pressure but not the leak point volume was significantly different between wet and dry patients. From these studies we determined that in the areflexic group leak point pressure was useful to predict incontinence, whereas in the hyperreflexic group leak point volume was more useful. The addition of the measurement of leak point pressure and leak point volume during routine urodynamic studies in myelodysplastic patients enhances accurate diagnosis and may select those who will best benefit from bladder augmentation and/or a procedure to increase outlet resistance. PMID- 8510241 TI - Urogenital rhabdomyosarcoma in children: is a conservative surgical approach justified? AB - Between 1970 and 1990, 23 patients were treated for embryonal rhabdomyosarcoma of the bladder (8), prostate (7), uterus (4) or vagina (4). One girl underwent exenteration without chemotherapy. Of the patients 22 received chemotherapy as initial treatment. There was 1 treatment-related death. A total of 21 patients completed the first phase: 4 were treated with chemotherapy alone and 17 subsequently underwent an operation. Three boys underwent total cystoprostatectomy and local resection was performed in 14 patients. One boy was lost to followup. Mean followup was 11.2 +/- 6.3 years in 15 survivors. Complete remission was achieved in 19 patients, while 11 (53%) had relapse at an interval of 3 to 102 months. Of 13 patients with bladder and prostate tumors 8 had relapse and 7 survived. Of 8 patients with uterus and vagina tumors 3 had relapse and all survived. Six patients died of recurrent disease (overall mortality rate 32%). The interval from initial diagnosis until death was always less than 5 years. The mortality rate was greater in boys (5 of 12) than in girls (1 of 9). Preservation of pelvic organs in girls was 75%, while of the boys 44% retained the bladder. Since disease relapsed in patients in whom no tumor was found in the resection specimen after chemotherapy, we conclude that a conservative surgical approach combined with chemotherapy towards urogenital rhabdomyosarcoma is justified. Although late relapses do occur, they can usually be salvaged by a combination of chemotherapy, radiotherapy and surgery. PMID- 8510242 TI - Perinephric panniculitis. AB - Panniculitis is an inflammatory condition of adipose tissue that is mainly seen subcutaneously or intra-abdominally. There have been rare case reports of retroperitoneal involvement but no reported cases of perinephric panniculitis. To our knowledge we report the first documented case of perinephric panniculitis. PMID- 8510243 TI - Laparoscopic marsupialization of massive renal cyst. AB - Laparoscopic approaches to urological problems continue to increase. We describe laparoscopic marsupialization and fulguration of a symptomatic giant renal cyst. Transient obstruction at the marsupialized window illustrated the importance of using omental or epiploic fat to maintain patency. Complete resolution of the cyst and hydronephrosis ensued. PMID- 8510244 TI - Renal transplantation from living related donor after excision of angiomyolipoma of the donor kidney. AB - A 44-year-old woman with end stage renal disease underwent living related renal transplantation after planned partial nephrectomy of the donor kidney for angiomyolipoma. PMID- 8510245 TI - The management of isolated renal recurrence of renal cell carcinoma following complete response to interleukin-2 based immunotherapy. AB - The role of interleukin-2 based immunotherapy in advanced renal cell carcinoma is gradually expanding. Among patients who achieve significant responses to these regimens the subsequent development of isolated recurrences raises difficult management questions. We report 2 unusual cases of isolated recurrence in the remaining kidney following a sustained, complete response to interleukin-2 based adoptive immunotherapy. Both patients were treated with interleukin-2 based therapy following surgical resection of the primary renal tumor. The disease course of each patient is described and the literature is reviewed. Both patients were free of disease after relatively short-term followup. Surgery for patients with limited recurrence of renal cell carcinoma following an objective response to immunotherapy may, in select cases, be a reasonable treatment alternative. PMID- 8510246 TI - Benign schwannoma of the retroperitoneal space: case report. AB - We report a case of retroperitoneal benign schwannoma involving the left femoral and obturator nerves. The difficulties of diagnosis are discussed and the potential complications of tumor removal are described. PMID- 8510247 TI - Renal hemodynamics in patients with obstructive uropathy evaluated by duplex Doppler sonography. AB - Duplex Doppler sonography was performed to differentiate varied degrees of obstructive uropathy by demonstrating the intrarenal arterial impedance in terms of pulsatility index and resistive index. We evaluated 56 kidneys in 28 normal subjects and 53 kidneys in 27 patients with unilateral or bilateral obstructive uropathy. The degrees of renal obstruction were determined by clinical criteria, such as excretory urography, antegrade pyelography and/or retrograde ureteral catheterization. There was excellent positive correlation between pulsatility index and resistive index values (correlation coefficient 0.77, p < 0.001). In patients with obstructive uropathy there were significant differences in pulsatility index and resistive index values between the 33 obstructed and 20 nonobstructed kidneys (p < 0.001 for both indexes). Significant differences were also found between the obstructed kidneys and the kidneys of normal subjects (p < 0.001 for both indexes) even after controlling for the age factor (p < 0.001). No difference was found between the nonobstructed kidneys of the patient group and those of normal subjects (p = 0.58 and 0.45 for pulsatility and resistive indexes, respectively). The resistive index values correlated well with the degrees of obstruction (p < 0.001). The mean resistive index values for mildly and significantly obstructed kidneys were 0.64 +/- 0.08 and 0.74 +/- 0.05, respectively. More than 93.3% of the significantly obstructed kidneys had resistive index values greater than or equal to 0.70. The obstruction may be significant and demands surgical intervention when the resistive index reaches that value. In contrast, with resistive index values of less than 0.70 renovascular resistance is minimally altered and obstruction may be mild. The results can be applied clinically to help justify the indications for surgical intervention to relieve symptoms of obstructive uropathy. PMID- 8510248 TI - Carbohydrate antigen 19-9 and carcinoembryonic antigen-producing transitional cell carcinoma of the ureter and bladder: a case report. AB - We report a case of transitional cell carcinoma of the ureter and bladder that produced carbohydrate antigen 19-9 and carcinoembryonic antigen. The serum levels of these antigens were elevated in this patient and an immunohistochemical examination revealed that the carcinoma cells stained positively for both antigens. PMID- 8510249 TI - Covered exstrophy with sequestered colonic remnant. AB - We report on a woman who presented with urinary incontinence, covered exstrophy and an abdominal mass. Radiographic studies and cystoscopy confirmed that the anterior abdominal mass did not communicate with the bladder or colon and that the gastrointestinal tract was normal. Subsequent surgical resection of the mass and Young-Dees-Leadbetter bladder neck reconstruction were performed. Histological examination of the mass revealed colonic mucosa. The etiology of the covered exstrophy and sequestered colonic remnant is discussed. PMID- 8510250 TI - Psoas abscess following intravesical bacillus Calmette-Guerin for bladder cancer: a case report. AB - An 87-year-old man with an abdominal aortic aneurysm received intravesical bacillus Calmette-Guerin therapy for transitional cell carcinoma of the bladder. He presented 9 months later with a psoas abscess that mimicked a contained retroperitoneal abdominal aortic aneurysm rupture. The abscess cultures yielded Mycobacterium bovis. Recent transurethral resection and high voiding pressures after instillations of bacillus Calmette-Guerin may have led to distant dissemination of the drug. PMID- 8510251 TI - Gangrene of the penis after implantation of penile prosthesis: case reports, treatment recommendations and review of the literature. AB - We report 3 cases of gangrene of the penis seen at our institution after penile prosthesis implantation. All 3 patients had insulin-dependent diabetes mellitus. Amputation was required in 2 patients. Aggressive debridement in conjunction with hyperbaric oxygen prevented amputation in the third patient. PMID- 8510252 TI - The management of meatal obstruction due to Kaposi's sarcoma of the glans penis. AB - Kaposi's sarcoma involving the glans penis was first described in 1902, with a subsequent report of meatal disease in 1943. With the recognition of the acquired immunodeficiency syndrome, genital lesions are becoming more frequently reported, with 51 cases cited in the literature. To date only 4 additional cases of meatal or fossa navicularis involvement have appeared in the literature, 3 of which described difficulty with micturition. We report a case of Kaposi's sarcoma involving the urethral meatus resulting in documented outflow obstruction, relieved with simple urethral serial dilation performed on an outpatient basis followed by intermittent obturation. We believe that this therapy represents a low risk, cost-effective treatment modality aimed at resolution of symptoms and alleviation of a potential source of infection in the patient with the acquired immunodeficiency syndrome. PMID- 8510253 TI - Genital swelling secondary to leakage from continuous ambulatory peritoneal dialysis: computerized tomography diagnosis. AB - We report a case of acute genital swelling in a patient receiving continuous ambulatory peritoneal dialysis. Physical examination did not identify or localize any defect. Computerized tomography demonstrated extravasation into the left groin and scrotum. Surgical repair of an inguinal hernia resulted in complete resolution of the genital swelling. PMID- 8510254 TI - Re: Diagnosis of interstitial cystitis. PMID- 8510255 TI - Endourological management of upper tract urothelial tumors. AB - Advances in ureteroscopic and percutaneous techniques have made it possible to treat many upper tract malignancies by conservative, parenchyma sparing surgery. Percutaneous techniques generally allow for easier and better access to the renal pelvis and improved tumor resection. However, concerns for tumor spillage and nephrostomy tract seeding make the ureteroscopic approach best for initial management of accessible renal pelvic lesions, particularly when the diagnosis is unclear. Ureteral tumors, especially those arising in the lower third of the ureter, are technically easier to treat endoscopically than are renal pelvic tumors. Fulguration or laser photocoagulation may be used to ablate the tumor following cold-cup biopsy for histological diagnosis. Supplemental therapy using laser treatment of the tumor base, and postoperative instillation of BCG and mitomycin C offer great potential benefit in terms of improved tumor control. Confirmation of such benefit awaits the results of larger trials. Presently, standard nephroureterectomy remains the procedure of choice for most transitional cell carcinomas of the upper urinary tract in patients with a normal contralateral kidney. For those with a solitary kidney, renal insufficiency, bilateral tumors or severe intercurrent disease preventing a major open operation conservative management using endoscopic techniques is a viable alternative. Overall, it appears that grade and stage are far more important determinants of long-term out-come than the type of operation in those with transitional cell carcinoma of the upper urinary tract. For this reason, some physicians have recommended conservative management of low grade, noninvasive lesions even in the face of a normal opposite kidney. However, the majority of patients with upper tract urothelial tumors are best treated by nephroureterectomy, which leads to a low risk of local recurrence and obviates the need for rigorous postoperative upper tract surveillance. PMID- 8510256 TI - Re: Intravesical lidocaine: topical anesthesia for bladder mucosal biopsies. PMID- 8510257 TI - Re: Total prostatoseminal vesiculectomy in the treatment of debilitating perineal pain. PMID- 8510258 TI - Retraction. Significance of asymptomatic bacteriuria in spinal cord injury patients on condom catheter. PMID- 8510259 TI - Characteristics of the glutathione/glutathione-S-transferase detoxification system in melphalan resistant human prostate cancer cells. AB - Glutathione (GSH) and glutathione-S-transferases (GST) have been implicated in resistance of tumor cells to certain alkylating agents, including melphalan. Glutathione levels and GST activities were determined in melphalan-resistant sublines of the human prostate carcinoma cell lines DU 145, PC-3 and LNCaP produced by serial treatment with melphalan at progressively increasing concentrations. The resistant sublines M4.5DU145, M5DU145, M6DU145, M6PC-3 and M6LNCaP were 27-, 7-, 3-, 6- and 2-fold more resistant to melphalan than the parental lines. The melphalan-resistant DU 145 and PC-3 lines showed cross resistance to cisplatin and tetraplatin, but retained sensitivity to vinblastine, colchicine and etoposide. Interestingly, both sublines were also resistant to methotrexate and adriamycin. The melphalan-resistant LNCaP line showed slight resistance to cisplatin and adriamycin, but remained sensitive to tetraplatin and methotrexate. This line also retained sensitivity to vinblastine while developing resistance to colchicine. Intracellular GSH levels were increased 2.8 fold for M5DU145, 1.7 fold for M6PC-3 and 2.1 fold for M6LNCaP compared to the parental lines, whereas GST activity using chlorodinitro-benzene as a substrate was comparable for all lines. When cumene hydroperoxide was used as a substrate, an increase in GST activity was noted only in the M6PC-3 line as compared with the parent line. Western blot analysis showed no change in GST isozyme profile between parent and resistant DU 145 lines; however a mu class isoenzyme was detected in the resistant, but not in the parent PC-3 line, using a Yb1 antibody. M5DU145 cells maintained in the absence of melphalan for seven months maintained their resistance to melphalan. Depletion of GSH, with buthionine sulfoximine, to control levels reversed melphalan resistance to control levels. PMID- 8510260 TI - Pelvic plexus denervation in rats causes morphologic and functional changes of the prostate. AB - The effect of pelvic plexus denervation on biochemical, morphologic and functional characteristics of the rat prostate was assessed in 11 adult Sprague Dawley rats. Unilateral denervation was performed by removing the right pelvic ganglion from the surface of the prostate; the contralateral lobe was similarly dissected, but not denervated, to serve as a control. After 15 to 18 days, the prostate was excised and specimens from both sides were used for morphologic (light and electron microscopy) and biochemical studies (sodium-dodecylsulfate polyacrylamide gel electrophoresis). With light microscopy, histologic features of the denervated prostate showed an overall decrease in cell height and a reduction of the clear apical area of the supranuclear region. At an ultrastructural level, denervated prostatic epithelial cells showed a slight, but significant, reduction in the number of secretory granules, a decrease in the height of the supranuclear region, and fewer and less abundantly dilated apical cisternae of endoplasmic reticulum. These changes indicate a modification of the secretory activity and reflect a change in epithelial metabolism, which was further supported by the results of SDS gel electrophoresis: the denervated prostate tissue showed an increase in the expression of 108 kDa and 80 kDa protein bands and a decrease in the expression of the 45 kDa protein band. This modification in the protein content is probably temporal and would undergo further evolution with time. The finding that denervation of the prostate causes significant morphologic and functional changes of the glandular epithelium strongly suggests that prostate function is not subject solely to the regulatory influence of the hormonal milieu. It is also dependent on the anatomical and, quite possibly functional, integrity of the nervous system. PMID- 8510261 TI - Does the administration of systemic radiographic contrast media influence the acute changes in renal physiology following exposure to extracorporeal shock waves in dogs? AB - Five anesthetized dogs were studied for 4 to 5 hours after administration of extracorporeal shock waves to one kidney, the contralateral organ serving as control. Repetitive major doses of the nonionic monomeric radiographic contrast medium (CM) iohexol were injected intravascularly before and after application of the extracorporeal shock waves for further provocation of kidney function. Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG) and kallikrein, clearances of creatinine, inulin and para-amino-hippuric acid (PAH), serum aldosterone level and plasma renin activity (PRA) were determined. On the exposed side there was a significant fall in urinary osmolality. Effective renal plasma flow (ERPF) was reduced and glomerular filtration rate (GFR) was unchanged; thus filtration fraction (FF) was increased. Extraction of PAH was reduced, and true renal plasma flow was unchanged. Urinary osmolality on the control side was unchanged. There was a fall in ERPF and increased GFR; therefore, FF increased. The mean rise of PRA in the exposed kidney was significant after shock waves. Urine volume and urinary excretion of electrolytes and kallikrein were stable bilaterally. Relating the results to those obtained in identical canine experiments without CM, simultaneous administration of CM does not seem to significantly influence the changes in kidney function parameters caused by extracorporeal shock waves in the dog. PMID- 8510262 TI - Post-transplant lymphoceles: a critical look into the risk factors, pathophysiology and management. AB - To define better the prevalence and pathophysiology of lymphoceles following renal transplantation, we prospectively evaluated 118 consecutive renal transplants performed in 115 patients (96 cadaveric, 22 living-related, 7 secondary and 111 primary). Ultrasonography was performed post-operatively and during rehospitalizations or whenever complications occurred. Perirenal fluid collections were identified in 43 patients (36%). Lymphoceles with a diameter of 5 cm. or greater were identified in 26 of 118 cases (22%). Eight patients (6.8%) had symptomatic lymphoceles requiring therapy. The interval for development of symptomatic lymphoceles was 1 week to 3.7 years (median 10 months). Risk factors for the development of lymphoceles were examined by univariate and multivariate analysis, and included patient age, sex, source of transplants (cadaver versus living-related donor), retransplantation, tissue match (HLA-B/DR), type of preservation, arterial anastomosis, occurrence of acute tubular necrosis-delayed graft function, occurrence of rejection, and use of high dose corticosteroids. Univariate analysis showed a significant risk for the development of lymphoceles in transplants with acute tubular necrosis-delayed graft function (odds ratio 4.5, p = 0.004), rejection (odds ratio 25.1 p < 0.001) and high dose steroids (odds ratio 16.4, p < 0.001). When applying multivariate analyses using stepwise logistic regression, only rejection was associated with a significant risk for lymphoceles (symptomatic lymphoceles--odds ratio 25.08, p = 0.0003, all lymphoceles--odds ratio 75.24, p < 0.0001). When adjusting for rejection, no other risk factor came close to being significant (least p = 0.4). Therapy included laparoscopic peritoneal marsupialization and drainage in 1 patient, incisional peritoneal drainage in 4 and percutaneous external drainage in 3 (infected). All symptomatic lymphoceles were successfully treated without sequelae to grafts or patients. We conclude that allograft rejection is the most significant factor contributing to the development of lymphoceles. Therapy of symptomatic lymphoceles should be individualized according to the presence or absence of infection. PMID- 8510263 TI - Analysis of regional norepinephrine content in the rabbit bladder after acute electrical pelvic floor stimulation. AB - Experiments were carried out to evaluate the regional norepinephrine (NE) content of the rabbit bladder after acute electrical pelvic floor stimulation (EPFS). After 30 minutes of EPFS, the content of NE increased significantly in both the bladder base and body (p < 0.05). Furthermore, this increased NE content continued for 1 to 2 hours after cessation of stimulation. The content of NE in the bladder base and body in rabbits treated with alpha-methyl-paratyrosine (AMT) was lower than in the control group. Application of EPFS increased NE content in the bladder even in animals pretreated with AMT. Based on these findings, during EPFS the hypogastric nerve would be presumed to play a significant role in bladder inhibition. Increased synthesis of NE probably did not play an important role in elevation of NE content after EPFS. PMID- 8510264 TI - Role of organic matrix in urinary stone formation: an ultrastructural study of crystal matrix interface of calcium oxalate monohydrate stones. AB - Human calcium oxalate monohydrate (COM) urinary stones were decalcified by treatment with a mixture of ethylenediaminetetraacetic acid (EDTA) solution and Karnovsky's fixative after embedding in bactoagar. Decalcified stones were examined by light microscopy, and also by scanning and transmission electron microscopy. Stones had distinct nuclei that were occupied by amorphous or apatitic calcium phosphate or aggregates of spherulitic COM crystals. EDTA insoluble matrix was ubiquitous in stones and consisted largely of finely matted fibrous material. It was organized in concentric laminations in the peripheral area of the stone but appeared highly disorganized in the stone center. Crystals were replaced by crystal ghosts. Organic matrix was present both inside the crystals and in the intercrystalline spaces. The study indicates a very close association between crystals and organic matrix. The relationship appears to begin early in crystal formation and persists throughout the formative and growth phases of the urinary stones. PMID- 8510265 TI - An experimental model of neonatal testicular torsion: evidence against an exclusively extravaginal etiology. AB - The present study was designed to determine whether extravaginal torsion of the spermatic cord (EVT) can be distinguished from intravaginal torsion (IVT) on the basis of gross and histologic examination of the testis. It is traditionally believed that EVT, postulated to occur only in neonates, can be grossly distinguished from IVT, which occurs in older patients, on the basis of adherence between testis and tunica vaginalis. Such adherence is felt to be present in EVT but not IVT. This concept that the two types of torsion can be distinguished in the operating room has important clinical ramifications. In cases of EVT, contralateral orchidopexy theoretically need not be performed, since adhesions develop between tunica vaginalis and dartos by a few weeks of age. This is in contrast to IVT, in which contralateral orchidopexy is necessary due to the bilateral nature of the bell clapper deformity. Using a rat model, we first demonstrated that IVT could produce adherence of the tunica vaginalis to testis. Then, eight rats were operated on, producing right IVT and left EVT. Animals were then sacrificed at intervals of up to one month. Gross and histologic examination showed involvement of the tunica vaginalis in an ischemic and inflammatory response in a majority of testes, regardless of the type of torsion. Attempts to distinguish EVT from IVT on the basis of grossly evident adhesions between tunica vaginalis and testis are of questionable validity. Early contralateral orchidopexy is therefore recommended in all cases of neonatal torsion. PMID- 8510266 TI - Characterization of calcium channel blocker induced smooth muscle relaxation using a model of isolated corpus cavernosum. AB - Several classes of smooth muscle relaxing agents have proven effective in relaxing cavernosal smooth muscle and useful in the pharmacotherapy of erectile dysfunction. The purpose of this investigation was to determine whether the calcium channel blockers (CCB) relax cavernosal smooth muscle. Thirty-two rabbit cavernosal strips were contracted by electrical field stimulation, and contraction inhibition was tested in response to cumulative doses (10(-8) M. to 10(-4) M.) of verapamil (V), diltiazem (D), isradipine (I), nicardipine (Nc) and nifedipine (Nf). All of the calcium channel blockers were effective at inhibiting electrically induced contractions (p < 0.0001 when CCB was compared with control; p < 0.05 when V or D was compared with I, Nc or Nf). Sixteen cavernosal strips were precontracted with 10(-5) M. norepinephrine. Relaxation in response to cumulative doses of each CCB was determined. Verapamil and the dihydropyridines (isradipine, nicardipine and nifedipine), but not diltiazem, were effective at relaxing norepinephrine induced contractions at 10(-5) and 10(-4) M. with verapamil most effective at 10(-4) M. concentration (p < 0.0001 by ANOVA at both concentrations when V, I, Nc, or Nf was compared with control). Sixteen cavernosal strips were incubated in solutions of 10(-5) and 10(-4) M. of each CCB followed by cumulative addition of norepinephrine (concentration range 10(-8) to 10(-4) M.). Preincubation with CCB did not affect the concentration of norepinephrine at which 50% of maximal cavernosal contractile response occurred (ED50). Maximum active tension of norepinephrine induced contractions was moderately decreased after CCB preincubation with 10(-4) M. of each dihydropyridine. It is concluded that the calcium channel blockers are effective in relaxing cavernosal smooth muscle and therefore possess potential as intracavernous pharmacotherapeutic agents for the treatment of erectile dysfunction. Verapamil appears to be the best candidate for further testing and clinical trial. PMID- 8510268 TI - Tracking the natural history of infantile hydronephrosis with diuretic renography. PMID- 8510267 TI - p53 gene alterations in human prostate carcinoma. AB - Alterations of the p53 gene are among the most frequent genetic lesions in a variety of human malignancies. Their role in prostate cancer is, however, unclear. We have analyzed 10 primary and two metastatic human prostate carcinomas as well as 3 prostate cancer cell lines for mutations of the p53-gene. Using single strand conformational polymorphism analysis (SSCP) and direct sequencing of the polymerase chain reaction (PCR) products, p53 mutations were detected in 1 of 10 primary prostate cancers. By contrast, 1 of 2 metastatic tumors and all 3 prostate cancer cell lines (derived from metastases) were found to contain a mutant p53 gene. Thus, our data suggest that alterations of the p53 gene at the mutational "hot spots" appear to occur infrequently in primary human prostate cancer, but may emerge in later stages of tumor progression. Furthermore, we confirm that loss of heterozygosity at a locus telomeric to p53, but not including p53, is associated with metastatic progression in 1 case. PMID- 8510269 TI - Extracorporeal shock wave lithotripsy in morbidly obese patients. AB - Management of urolithiasis in morbidly obese patients is usually associated with higher morbidity and mortality compared to nonobese patients. In morbidly obese patients, since the kidney and stone are at a considerable distance from the skin (compared to nonobese patients), difficulty may be encountered in positioning the patient so that the stone is situated at the F2 focal point of the lithotriptor. Using various aids, such as the extended shock pathway and abdominal compression, we treated 81 patients weighing more than 300 pounds using the Medstone STS tubless second generation lithotriptor. The stone-free rate at 3 months or longer was 68%, with another 10% having asymptomatic fragments of 4 mm. or less in diameter. Thus, a clinical stone-free rate of 78% was achieved. The retreatment rate was 11% and the post-lithotripsy secondary procedures rate was 3%. Since these results are comparable to those obtained when treating patients less than 300 pounds, extracorporeal shock wave lithotripsy can be used successfully to treat urolithiasis in morbidly obese patients. PMID- 8510270 TI - Ureteropelvic junction disruption following blunt abdominal trauma. AB - Disruptions of the ureteropelvic junction following blunt abdominal trauma are rare. Our recent management of 8 cases (7 patients) revealed that an immediate diagnosis of this entity was made in less than 50% of the patients. The majority of delayed diagnoses occurred when the patients experienced absence of hematuria associated with nonresponsive hypovolemic shock. The clinical instability of the patients required emergency celiotomy for stabilization and precluded our obtaining appropriate contrast enhanced radiographic studies. Retroperitoneal findings at operation failed to reveal evidence of a perinephric hematoma. The kidneys were palpably normal and, therefore, they were not directly examined. Despite these negative retroperitoneal findings the patients sustained disruption of the ureteropelvic junction. Therefore, we stress that a negative exploratory laparotomy without direct visualization of the kidney should not exclude radiographic evaluations for retroperitoneal injuries. PMID- 8510271 TI - Percutaneous antegrade dilation of ureteral strictures in kidney transplants. AB - Transplant ureteral stricture can be treated by either incisional surgery or percutaneous endoluminal dilation. We present 17 cases of percutaneous antegrade endoluminal dilation. The results of this procedure were satisfactory, with a 70% success rate that seems to be maintained during long-term followup. The results were better if dilation was done on a short and recent juxta-anastomotic stricture stented with a 10F Double-J* catheter for 2 months. PMID- 8510272 TI - The ileal neobladder: 6 years of experience with more than 200 patients. AB - Between April 1986 and April 1992, 211 consecutive men underwent lower urinary tract reconstruction by means of the ileal neobladder. There have been 5 perioperative deaths for an operative mortality rate of 2.4%. The early complication rate for issues not directly related to the neobladder was 7.5% compared to a 6.5% directly neobladder-related early reoperation rate. Neobladder related late complications requiring rehospitalization or reoperation have been acceptable, including ileus (2%), abscess (1%), colon-reservoir fistula (1.5%), hydronephrosis (1%), ureteral stenosis (3.6%) and transurethral incision of the urethroileal anastomosis (7%). Overall, only 29.3% of our patients had no complication, whereas 32% suffered significant problems requiring rehospitalization or reoperation. The remainder of the patients suffered minor but not negligible problems. Excellent continence was achieved early and increased with time: 85% of the patients were perfectly dry night and day by 3 years. At this date only 5.5% of the patients had nighttime incontinence, while 6% wear protection for occasional accidents. Intermittent catheterization is necessary in 3.5% of the patients because of the inability to void or maintain a post-void residual volume of less than 100 ml. Despite the fact that some price must be paid for excellent continence, natural voiding and undisturbed body image, the ileal neobladder continues to be our procedure of choice for male patients after cystectomy provided there is no evidence of prostatic or urethral involvement. Our results should stimulate earlier patient and physician acceptance of cystectomy. PMID- 8510273 TI - The gastroileoileal pouch: an alternative continent urinary reservoir for patients with short bowel, acidosis and/or extensive pelvic radiation. AB - We report on 6 patients who underwent a new type of continent urinary diversion: the gastroileoileal reservoir. These are a select group of patients who presented with the short bowel syndrome, acidosis, borderline diarrhea and/or severe pelvic radiation, which precluded the use of terminal ileum and the ileocecal segment. Considering these factors, and based on the different functional properties of the stomach as well as the need for a large reservoir, a segment of stomach and proximal ileum was used to construct the reservoir. Four patients have been followed for at least 6 months, with the longest followup being 12 months. Temporary dysphagia requiring hydrogen blockers developed in 1 patient. Results indicate excellent function of the continent urinary system, lack of metabolic complications, absent diarrhea and excellent patient tolerance. This procedure could be a useful alternative in some difficult clinical situations when continent urinary diversion is desirable. PMID- 8510274 TI - Long-term followup of the Kock and Indiana pouch procedures. AB - Between 1984 and 1991, 115 consecutive patients underwent cutaneous continent urinary diversion comprising 76 Kock and 39 Indiana pouch procedures. The 2 different forms of achieving continent urinary diversion were subsequently compared in a long-term followup that evaluated complications, including pouch function and the need for revisions. In the Kock pouch group there were 14 (18.4%) early postoperative complications (3 months), which required 4 subsequent reoperations (5.3%). The Indiana pouch group had a similar incidence of early complications (17.9%) but there were no reservoir related problems. The long-term study group comprised 68 Kock and 37 Indiana pouch patients who were observed for 12 months or longer (mean followup 53 and 34 months, respectively). Of 9 efferent nipple valve malfunctions observed in the Kock pouch group 5 required surgical revision. Of 16 complications related to afferent limb function 15 were caused by the use of polyester fiber fabric for the anchoring collar and 8 of these 15 complications required surgical revision. The first 2 Indiana pouch patients had pouch deformities due to incomplete detubularization of the cecum that required surgical repair. Overall, surgical revisions, including minor repairs, were performed on 15 Kock pouch patients (22.1%) and 4 Indiana pouch patients (10.8%). Both forms of the procedure preserved continence to a satisfactory degree. Urinary tract stones developed in 18 patients (26.5%) from the Kock pouch group, usually on the exposed staples or the eroded, nonabsorbable collar used to construct the nipple valves. Stone formation was rare (5.4%) in the Indiana pouch group. The incidence of ureteral implantation stricture was low in both procedures. There was no significant difference in the incidence of bacteriuria between the 2 methods of urinary diversion. These data demonstrate that the Kock pouch and Indiana pouch procedures can be accomplished with the same early postoperative complication rate. Our 8-year experience showed a high incidence of Kock afferent nipple valve malfunction. However, most of these malfunctions were due to the use of a nonabsorbable collar and can be avoided. When taking this into account, therefore, it can be concluded that the Indiana pouch functions as well as the Kock pouch with roughly the same incidence of late complications and the same reoperation rate but with a lower incidence of stone formation. PMID- 8510275 TI - Transvaginal repair of vesicovaginal fistula using a peritoneal flap. AB - Even complex vesicovaginal fistulas may be repaired transvaginally. In difficult repairs adjunctive measures have been described to increase the success rate of surgery, including Martius flaps, labial flaps or gracilis muscle flap. We describe a new technique to repair difficult vesicovaginal fistulas via a transvaginal approach. A flap of peritoneum is developed and used to buttress the fistula repair. This repair was successful in 9 of 11 patients (82%). Complications occurred in only 1 patient who suffered a bladder diverticulum containing a stone. The major advantage of this technique is its simplicity and lack of an extravaginal harvesting incision. This repair is particularly well suited for complex, high lying vesicovaginal fistulas. PMID- 8510276 TI - Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer. AB - The ultimate goal of prognostic assessment is optimization of individual counseling. Often, however, studies on prognostic factors focus on discriminating between high risk and low risk subgroups without considering the relevance of 1 or more factors for predicting disease outcome in individual patients. We quantified the accuracy of prediction of future recurrences and disease progression in individual patients with primary superficial bladder cancer. The study cohort consisted of 1,674 patients who were followed prospectively between 1983 and 1991 in the Netherlands. By analyzing half of the patients with proportional hazards regression, we computed relative risks of recurrence and progression. A prognostic index score based on these relative risks was then applied to the other half of the patients to determine whether group outcome could be predicted accurately. To assess the accuracy of prediction in individuals we used a method similar to the construction of receiver operating characteristic curves in diagnostic test assessment. The 3-year risk of first recurrence was 55% (95% confidence interval 51 to 59%). The 3-year risk of first progressive disease was 10% (95% confidence interval 8 to 12%). For the risk of first recurrence, tumor stage, tumor extent and multicentricity had statistically significant prognostic ability. Prognostic factors for the risk of disease progression were tumor stage, grade, multicentricity and the result of random biopsies from cystoscopically normal-appearing urothelium. For patients with a prognostic index score that suggested a low risk for recurrent and progressive disease the predicted 3-year risk of first recurrence was still 44% but the predicted 3-year risk of progression was only 3%. For patients with a prognostic index score that suggested a high risk the predicted risks were 74% and 22%, respectively. These predicted risks appeared to be fairly accurate when applied to the other half of our case series. However, in any 2 patients chosen at random the chance that the patient with the worst predicted prognosis would have a shorter recurrence-free and progression-free followup was calculated to be only 58% and 67%, respectively. Although the available prognostic factors in superficial bladder cancer may be useful to identify high risk and low risk subgroups, predictability in individuals is highly inaccurate. More relevant prognostic factors are needed to decrease current overtreatment and undertreatment rates, and to improve the followup policy. PMID- 8510277 TI - Cisplatin, methotrexate and vinblastine plus surgical restaging for patients with advanced transitional cell carcinoma of the urothelium. AB - Chemotherapy with cisplatin, methotrexate and vinblastine (CMV) is active in advanced transitional cell carcinoma of the urothelium. Aggressive surgical resection of residual disease following responses produced by CMV was incorporated into a combined modality approach. Between 1982 and 1990, 64 patients were entered into the study. Of 55 patients evaluable for response 11 (20%) had a pathological complete response, 14 (25%) achieved a complete response following resection of residual disease and 5 (9%) whose disease was not surgically restaged had a clinical complete response. The overall complete response rate was 55%. Patients with liver, lung or bone involvement had significantly decreased survival compared to patients without visceral disease (p = 0.002). With a median followup exceeding 50 months, 14 patients (22% of all patients entered into the study) were free of disease at 23 to 98+ months. There were no deaths related to treatment. CMV produced high rates of response in patients with advanced disease, including those with distant metastases. Surgical resection of residual disease following responses produced by chemotherapy proved to be feasible, without treatment related mortality, and may have prolonged survival in selected cases. PMID- 8510278 TI - Management of low velocity gunshot wounds to the anterior urethra: the role of primary repair versus urinary diversion alone. AB - The management of partial transection of the anterior urethra following penetrating penile injuries is controversial. Optional therapeutic techniques range from a primary sutured reapproximation to urinary diversion alone. We recently managed 17 low velocity gunshot wounds to the external genitalia in which the missile traversed the penile corpus cavernosum, and was associated with less than 40% transection of the corpus spongiosum and anterior urethra. Nine patients were managed with suprapubic diversion, skin debridement and corporeal closure along with placement of a urethral catheter. Eight patients were managed by suprapubic diversion, debridement, closure of the corporeal bodies and a primary sutured reapproximation of the anterior urethra. Urethral strictures developed in 7 patients (78%) managed by a suprapubic tube and urethral stenting during an average followup of 20 months (range 18 to 24). In contrast, 1 patient (12%) managed by a sutured urethral approximation had a urethral stricture during an average followup of 20 months (range 18 to 30, p < 0.01). Our data support a significantly better prognosis for partial transection of the anterior urethra secondary to low velocity gunshot wounds if managed by aggressive wound debridement, corporeal repair, placement of a suprapubic catheter and primary repair of the urethra. PMID- 8510279 TI - The management of penile Mondor's phlebitis: superficial dorsal penile vein thrombosis. AB - Superficial dorsal penile vein thrombosis was diagnosed 8 times in 7 patients between 19 and 40 years old (mean age 27 years). All patients related the onset of the thrombosis to vigorous sexual intercourse. No other etiological medications, drugs or constricting devices were implicated. Three patients were treated acutely with anti-inflammatory medications, while 4 were managed expectantly. The mean interval to resolution of symptoms was 7 weeks. Followup ranged from 3 to 30 months (mean 11) at which time all patients noticed normal erectile function. Only 1 patient had recurrent thrombosis 3 months after the initial episode, again related to intercourse. We conclude that this is a benign self-limited condition. Anti-inflammatory agents are useful for acute discomfort but they do not affect the rate of resolution. PMID- 8510280 TI - New incision for penile surgery. AB - We present a recent modification of the surgical incision used for patients with Peyronie's disease of the dorsal penile shaft and/or who require a concomitant complete dorsal vein ligation procedure. This approach spares the penile skin from trauma and torsion, and allows for improved access to the more proximal penile shaft. Our experience to date has demonstrated no evidence of increased morbidity with excellent cosmetic results. PMID- 8510281 TI - Clinical experience of incidentally discovered adrenal tumor with particular reference to cortical function. AB - We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency. These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance. PMID- 8510282 TI - Tuberculous epididymitis and epididymo-orchitis: sonographic findings. AB - The findings at scrotal sonography in 10 patients with tuberculous epididymitis and in 2 with nontuberculous epididymitis are presented. In 6 patients with tuberculous epididymitis the testes were also involved (epididymo-orchitis). The most notable sonographic findings of tuberculous epididymitis were an enlarged epididymis, predominantly in the tail portion, and marked heterogeneity of the echo texture of the involved epididymis. Sonographic findings of associated testicular involvement consisted of a diffusely enlarged hypoechoic testis or ill defined focal intratesticular hypoechoic areas, or an irregular margin between the testis and epididymis. The sonographic findings encountered in patients with tuberculous epididymitis appear to be different from those encountered in nontuberculous epididymitis. Sonography might prove helpful in aiding the clinical distinction between these 2 forms of epididymitis and in demonstrating associated testicular involvement in tuberculous epididymitis. PMID- 8510283 TI - Psychiatrists set to approve DSM-IV. PMID- 8510285 TI - Injury prevention must be part of nation's plan to reduce health care costs, say control experts. PMID- 8510284 TI - 'Invisible' epidemic now becoming visible as HIV/AIDS pandemic reaches adolescents. PMID- 8510286 TI - Experts reveal national plan for injury control. PMID- 8510287 TI - From the Centers for Disease Control and Prevention. Infectious diseases update: outbreak, hantavirus infection--southwestern United States, 1993. PMID- 8510288 TI - A piece of my mind. Retrieval. PMID- 8510289 TI - Unfunded research? I am shocked, shocked! PMID- 8510290 TI - Unfunded research? I am shocked, shocked! PMID- 8510291 TI - Unfunded research? I am shocked, shocked! PMID- 8510292 TI - Unfunded research? I am shocked, shocked! PMID- 8510293 TI - Race and crack cocaine. PMID- 8510294 TI - Caffeine use during pregnancy: how much is safe? PMID- 8510295 TI - Baldness and myocardial infarction. PMID- 8510296 TI - The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma. AB - OBJECTIVE: To determine the effect of acute alcohol intoxication and chronic alcohol abuse on morbidity and mortality from trauma. DESIGN: Prospective cohort study. PATIENTS: Blunt or penetrating trauma patients at least 18 years of age admitted to one trauma center or dying at the injury scene. MAIN OUTCOME MEASURES: Mortality, complications (infection, pneumonia, respiratory failure, or multiple organ failure), and length of hospital stay. RESULTS: Acute intoxication had no effect on risk of dying--at the injury scene, within the first 24 hours of hospitalization, after the first 24 hours, or overall. Acute intoxication also did not increase the risk of complications and was associated with shorter lengths of stay. Patients with both biochemical and behavioral evidence of chronic alcohol abuse had a twofold increased risk of complications, particularly pneumonia and any infection, compared with those with no evidence of chronic alcohol abuse. CONCLUSIONS: Chronic, but not acute, alcohol abuse adversely affects outcome from trauma. Attention to the problem of chronic alcohol abuse in trauma patients is necessary, and screening trauma patients for chronic alcohol abuse appears to be warranted. PMID- 8510297 TI - Outcome after allogeneic bone marrow transplant for leukemia in older adults. AB - OBJECTIVE: To determine whether age over 40 years is associated with adverse outcome after allogeneic bone marrow transplantation for leukemia. DESIGN: A retrospective analysis of outcome after bone marrow transplants for leukemia reported to the International Bone Marrow Transplant Registry (IBMTR) among recipients 30 through 39 years, 40 through 44 years, 45 through 49 years, and 50 years of age and older. SETTING: Transplantations performed in 138 institutions worldwide and reported to the IBMTR. PATIENTS: A total of 2180 recipients of HLA identical sibling bone marrow transplants for leukemia, divided into four cohorts based on age: 30 through 39 years (n = 1282), 40 through 44 years (n = 527), 45 through 49 years (n = 291), and 50 years and older (n = 80). MAIN OUTCOME MEASURES AND RESULTS: Incidence of leukemia-free survival, graft-vs-host disease, and relapse was comparable among the four age cohorts. Patients with advanced leukemia aged 45 years or older had a slightly higher risk of treatment-related mortality, and the 45- through 49-year-old cohort had a higher risk of interstitial pneumonia. CONCLUSIONS: These data indicate that among leukemia patients over 30 years of age at the time of allogeneic bone marrow transplantation, increasing age into the fifth decade does not adversely affect outcome after transplants from HLA-identical siblings. PMID- 8510298 TI - The effect of health coverage for uninsured pregnant women on maternal health and the use of cesarean section. AB - OBJECTIVES: Although there has been substantial policy interest in interventions to improve the neonatal outcomes of disadvantaged women, little attention has been paid to the health status of pregnant women themselves. We therefore examined whether the provision of health coverage to uninsured low-income pregnant women affects maternal health status or the use of cesarean section. DESIGN: Natural experiment in Massachusetts. PATIENTS: All in-hospital, single gestation births in 1984 (N = 57,257) and 1987 (N = 64,346). INTERVENTION: Healthy Start is a statewide health coverage program for uninsured pregnant women. In 1985, it covered women with incomes below 185% of the federal poverty level. MAIN OUTCOME MEASURES: Rates of adverse maternal outcome (severe pregnancy related hypertension, placental abruption, and a length of stay at least 1 day longer than infants' stay) and cesarean section for uninsured women, and for two concurrent control groups, women with Medicaid and women with private insurance. We calculated the difference in rates between the uninsured and each concurrent control. We then examined the change in these interpayer differences in rates between 1984 and 1987 to measure the effect of Healthy Start. MAIN RESULTS: In 1984, uninsured women had higher rates of adverse maternal health outcome than privately insured women (5.5% vs 5.1%, respectively; interpayer difference, 0.4%) and received fewer cesarean sections (17.2% vs 23.0%; interpayer difference, 5.8%). Between 1984 and 1987 there was no statistically significant change in the interpayer difference in adverse outcome relative to women with private insurance. However, the interpayer difference in cesarean sections between the uninsured and the privately insured was reduced by 2.3% (95% confidence interval [CI], +0.4% to +4.2%), although the uninsured continued to undergo fewer cesarean sections (22.4% vs 25.9%). Similar results were observed when the uninsured women were compared with women with Medicaid. CONCLUSIONS: The provision of health insurance alone to low-income pregnant women may not be associated with an improvement in maternal health. Expanded coverage was associated, however, with an increase in the rate of cesarean section. PMID- 8510299 TI - Pitfalls in the care of patients with tuberculosis. Common errors and their association with the acquisition of drug resistance. AB - OBJECTIVE: To determine, among a group of patients with multidrug-resistant pulmonary tuberculosis, whether there had been management practices that deviated from established guidelines, and whether these decisions were associated with the acquisition of multidrug resistance and adverse medical sequelae. DESIGN: Case series. SETTING: Referral center. PATIENTS: All patients with pulmonary tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine in 1989 through 1990. INTERVENTIONS: The records of all patients referred to this institution for the treatment of tuberculosis in 1989 through 1990 were reviewed to ascertain the nature of management decisions that might have been associated with the acquisition of drug resistance. MAIN OUTCOME MEASURES: Standards of practice as defined by the American Thoracic Society, the Centers for Disease Control and Prevention, and the American College of Chest Physicians were compared with these management decisions to determine whether "errors" had been made, resulting in treatment failure and the development of acquired drug resistance. RESULTS: Among the 35 study patients, errors were detected in the management decisions in 28; there was an average of 3.93 errors per patient. The most common errors were the addition of a single drug to a failing regimen, failure to identify preexisting or acquired drug resistance, initiation of an inadequate primary regimen, failure to identify and address noncompliance, and inappropriate isoniazid preventive therapy. The multidrug resistance acquired through the errors resulted in prolonged hospitalizations, treatment with more toxic drugs, and high-risk resectional surgery. The costs for this "salvage therapy" were extraordinary, averaging $180,000 per patient. CONCLUSIONS: Aggressive professional education, tighter control on the provisions of care for tuberculosis patients, and the committing of additional resources to tuberculosis control programs are vital in improving the care of tuberculosis patients and limiting the development of acquired drug resistance. PMID- 8510300 TI - Understanding patients' decisions. Cognitive and emotional perspectives. AB - OBJECTIVE: To describe ways in which intuitive thought processes and feelings may lead patients to make suboptimal medical decisions. DESIGN: Review of past studies from the psychology literature. RESULTS: Intuitive decision making is often appropriate and results in reasonable choices; in some situations, however, intuitions lead patients to make choices that are not in their best interests. People sometimes treat safety and danger categorically, undervalue the importance of a partial risk reduction, are influenced by the way in which a problem is framed, and inappropriately evaluate an action by its subsequent outcome. These strategies help explain examples where risk perceptions conflict with standard scientific analyses. In the domain of emotions, people tend to consider losses as more significant than the corresponding gains, are imperfect at predicting future preferences, distort their memories of past personal experiences, have difficulty resolving inconsistencies between emotions and rationality, and worry with an intensity disproportionate to the actual danger. In general, such intangible aspects of clinical care have received little attention in the medical literature. CONCLUSION: We suggest that an awareness of how people reason is an important clinical skill that can be promoted by knowledge of selected past studies in psychology. PMID- 8510301 TI - Cesarean delivery for women presenting with genital herpes lesions. Efficacy, risks, and costs. AB - OBJECTIVE: To assess the effect of cesarean delivery on neonatal and maternal morbidity and mortality and their associated costs for two populations of women presenting with genital herpes lesions at delivery: those with and those without a history of genital herpes. DATA SOURCES: MEDLINE (search for herpes simplex virus and neonatal, cesarean, and mortality) and recognized experts. DATA EXTRACTION: The quality of the overall data used for baseline values was graded using a predetermined scale. RESULTS: The practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in more than 1580 excess cesarean deliveries performed for every poor neonatal outcome prevented, a cost per neonatal herpes case averted of $2.5 million and a cost per quality-adjusted life-year gained of $203,000. For these women, lowering the efficacy of cesarean delivery or the herpes simplex virus vertical transmission rate could result in maternal deaths outnumbering neonatal deaths prevented. In contrast, cesarean delivery for women with no history of genital herpes simplex virus who have lesions at delivery has low maternal costs per neonatal benefit and saves money. CONCLUSIONS: Women who present with their first clinical episode of genital herpes at delivery should have a cesarean section performed. However, the current practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in high maternal morbidity and mortality at substantial financial expense, underscoring the urgency of examining alternative management strategies. PMID- 8510302 TI - NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. PMID- 8510303 TI - Missing the boat on drinking and boating. PMID- 8510304 TI - Alcohol's effect on trauma outcomes. A reappraisal of conventional wisdom. PMID- 8510305 TI - Role of cesarean delivery in preventing neonatal herpes virus infection. PMID- 8510306 TI - Usefulness of thallium-201 re-injection method for the evaluation of myocardial viability. AB - Areas of the heart which are supposedly absent of myocardial viability due to persistent thallium defect in exercise thallium myocardial scintigraphy sometimes recover ventricular wall motion through coronary revascularization. To avoid such underestimation of myocardial viability, a "re-injection method" was developed. At the peak of supine ergometer exercise in 51 patients with coronary artery disease, 111 MBq thallium was injected. Conventional exercise and 3 h-delay images were then obtained using single photon emission computed tomography. Subsequently, 55 MBq thallium was injected and a re-injection image was obtained 1 h later. Each image was divided into 12 segments and compared by left ventriculography and coronary angiography. Redistribution was found in 36 patients (71%) on the delayed images and in 44 patients (86%) on either the delayed or the re-injection images (p < 0.05). There were 127 redistribution segments (38%) on the delayed images and 163 (49%) on the re-injection images out of 336 defects on the exercise images (p < 0.001). In normokinetic segments with significant coronary stenosis and in hypokinetic segments, redistribution was found in 42% and 45% of the defects, respectively, on the delayed images, and in 65% and 62% of the defects, respectively, on the re-injection images (p < 0.01). However, no significant differences were observed between the delayed and either the delayed or re-injection images in the akinetic segments. These results suggest that the re-injection method is useful for avoiding underestimation of myocardial viability. PMID- 8510307 TI - Increased plasma endothelin concentrations in patients with acute heart failure after myocardial infarction. AB - We have investigated the relationship between plasma endothelin (ET) concentrations and several clinical characteristics in 31 patients with acute myocardial infarction (MI). ET levels were also measured in 10 age-matched healthy subjects, 9 patients with unstable angina, and 20 patients with chronic heart disease. In patients with MI, although no significant relationship was observed between plasma ET concentrations and measured hemodynamic parameters, plasma levels were higher in patients with pulmonary congestion than in those without this complication (1.61 +/- 0.29 vs 1.21 +/- 0.33 fmol/ml; p < 0.01). No significant difference in plasma ET levels was found between cardiac and peripheral sampling sites (pulmonary artery; 1.07 +/- 0.28, right atrium; 1.02 +/ 0.28, peripheral artery; 1.12 +/- 0.23, peripheral vein; 1.14 +/- 0.38 fmol/ml: N.S.), or among patients with uncomplicated MI, unstable angina (1.00 +/- 0.32 fmol/ml), and healthy subjects (1.01 +/- 0.29 fmol/ml). Increased level were observed in patients with decompensated heart failure due to chronic heart disease, but were not found in patients without pulmonary congestion (1.62 +/- 0.60 vs 1.11 +/- fmol/ml; p < 0.01). These observations suggest that plasma ET concentrations are elevated in the presence of congestive heart failure or severe ventricular depression, but are not persistently increased by myocardial ischemia per se. PMID- 8510308 TI - Ratio of lung to heart thallium-201 uptake on exercise and dipyridamole stress imaging in coronary artery disease--implication of SPECT. AB - To examine whether measurements of lung thallium-201 (Tl-201) uptake with single photon emission computed tomography (SPECT) following exercise or dipyridamole infusion provide complementary information as reported in planar imaging, we examined 140 patients undergoing exercise or dipyridamole Tl-201 SPECT and coronary arteriography for the diagnosis of coronary artery disease (CAD). On the reconstructed coronal tomographic image, regions of interest were placed over the left upper lung field and the left ventricular myocardium. Lung to heart ratio (L/H ratio) was calculated as a fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. An L/H ratio of larger than a value of mean +2 standard deviation, derived from patients without significant coronary stenosis, was considered as abnormal. The patients with abnormal L/H ratio on exercise Tl-201 SPECT had larger extent and severity scores of Tl-201 defects on the initial image, lower left ventricular ejection fraction, higher end-diastolic pressure and higher incidence of multi-vessel CAD than those with the normal ratio. However, in dipyridamole studies, abnormal L/H ratio did not relate to scintigraphic or hemodynamic severity. These data confirmed that increased lung Tl-201 uptake after exercise suggested the presence of extensive CAD or left ventricular dysfunction. However, L/H ratio might be less useful in dipyridamole studies. Thus, quantitative measurements of L/H ratio with exercise but not dipyridamole SPECT could provide additional information related to the involved cardiac pump performance in CAD. PMID- 8510309 TI - Fragmentation of internal elastic lamina and spread of smooth muscle cell proliferation induced by percutaneous transluminal coronary angioplasty. AB - We investigated smooth muscle cell proliferation associated with restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 8 arteries with fragmented internal elastic lamina obtained at autopsy in 7 patients who died between 2 months to 2 years 11 months after coronary angioplasty. The internal elastic lamina fragmentation, measured longitudinally along the blood vessels, measured 6.6 +/- 6.9 mm. Smooth muscle cell proliferation was concentrated around the fragmented internal elastic lamina, extending longitudinally even to unfragmented areas. The proliferation of smooth muscle cells extended for 1.8 +/- 2.2 mm in the proximal portion of the fragmentation, and for 2.0 +/- 2.9 mm in the distal portion. The possibility of new stenoses resulting from smooth muscle cell proliferation at sites adjacent to those subjected to PTCA should be borne in mind when PTCA of the proximal segments of the left anterior descending coronary artery is contemplated. PMID- 8510310 TI - Noninvasive evaluation of total occlusion of infarct-related coronary artery after a first myocardial infarction. AB - Previous studies have demonstrated that the long-term prognosis after acute myocardial infarction in patients whose infarct-related artery remains occluded is worse than that in those with anterograde flow. To determine how to identify patients with occluded infarct-related arteries noninvasively, 143 consecutive patients after a first myocardial infarction underwent exercise testing and dipyridamole thallium scintigraphy. The incidence of total occlusion was higher in inferior/posterior infarction than in anterior infarction (29/53 vs 28/90; p = 0.005). In patients with inferior/posterior infarction, discriminant analysis revealed a sensitivity of 79%, a specificity of 88% and an accuracy of 83% (p = 0.0005) in identifying those with an occluded infarct-related artery. In patients with anterior infarction, the analysis showed a sensitivity of 68%, a specificity of 85% and an accuracy of 79% (p < 0.0001) in identifying those with an occluded artery. These results indicate that noninvasive study may be useful in the evaluation of total occlusion of the infarct-related coronary artery. PMID- 8510311 TI - Solitary ostial coronary artery stenosis. AB - Among 125,000 patients who underwent coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988, 128 (0.1%) were found to have 50-99% stenosis of one or both coronary ostia. All cases were associated with minimal or no obstruction in the distal coronary arteries. Thirty-six percent were males and 64% were females. Fifty percent had ostial narrowing of the left main trunk, 41% had ostial narrowing of the right coronary artery, and 9% had bilateral ostial stenosis. Based on angiographic appearance, the patients were categorized into three groups: 1) atherosclerotic (77%), 2) primary (unknown etiology) (13%), and 3) secondary to aortic valve disease (10%). Compared with the other groups, primary solitary coronary ostial stenosis was commonly found in middle-aged premenopausal or postsurgical menopausal females who had few coronary risk factors and were experiencing severe angina symptoms. At autopsy, most cases were atherosclerotic, however, fibromuscular dysplasia may be found in primary solitary ostial stenosis. This rate entity is difficult to diagnose, and is associated with increased risk during cardiac catheterization and bypass surgery. Solitary ostial stenosis should be included in the differential diagnosis of ischemic heart disease, especially in young or middle-aged female patients. PMID- 8510312 TI - Morphological characteristics of hypertrophic cardiomyopathy estimated by left ventriculography. AB - To determine the common morphological characteristics of hypertrophic cardiomyopathy (HCM) by ventriculography from a right anterior oblique projection, diaphragmatic and free wall configurations were analyzed in 15 patients with obstructive HCM (HOCM), 32 patients with nonobstructive HCM (HNCM) and 17 controls. There was a convexity extending into the left ventricle in the right anterior oblique projection due to hypertrophy of the interventricular septum (IVS) in all patients with HCM. The peak convexity, where septal thickness was maximal (M point), was closer to the base in HOCM than in HNCM. Due to this convexity, the left ventricle showed a catenoid-shaped distortion at the M point. The distortion was severer in HOCM than in HNCM. Left ventricular free wall (LVFW) thickness was measured at the base and near the apex. LVFW thickness in HOCM decreased toward the apex, similar to that in controls, but in 17 of 32 HNCM (53%) LVFW thickness increased toward the apex. Cardiac index and stroke index in HCM were significantly smaller than those in controls. There was a significant correlation between the position of the M point and stroke index in HCM. These results indicate that a common morphological characteristic of HCM on the diaphragmatic side is the existence of a convexity extending into the left ventricle, and that cardiac performance in HCM is greatly influenced by the nature of the convexity. Myocardial abnormality seems to exist primarily at the base of the IVS in HOCM, and primarily in the lower part of the IVS and LVFW in HNCM. PMID- 8510313 TI - Biochemical remodeling of collagen in the heart of spontaneously hypertensive rats--prominent increase in type V collagen. AB - To determine how collagen is remodeled in the heart during the development of cardiac hypertrophy, the collagen concentration and the proportions of types I, III, and V collagen were analyzed in the hearts of 10-, 20-, 32-, and 40-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The collagen concentration was calculated after the hydroxyproline content was measured and the proportions of types I, III, and V collagen were determined by non interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the collagen concentrations in 10-week-old SHR and WKY. At 20 weeks, the collagen concentration in the hearts of the SHR had decreased significantly (p < 0.01) when compared to that in the WKY, at 40 weeks, this concentration in SHR had increased significantly (p < 0.05) when compared to that in the WKY. Type V collagen in WKY increased with age and type I collagen in the 20- and 40-week-old WKY decreased significantly (p < 0.05) when compared to that in the 10-week-old WKY. However, the proportion of type I collagen in the 20 week-old WKY did not differ from that of the 40-week-old WKY. There was no significant difference between the proportions of the various types of collagen in 10-week-old SHR and those in age- and sex-matched WKY. However, the proportion of type V collagen in the 20- and 40-week-old SHR was significantly (p < 0.01) higher than that in age- and sex-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510314 TI - Sequence in DNA synthetic phase ratio of spontaneous hypertensive rat (SHR) myocardium--study on development of cardiomegaly. AB - We studied the relative synthetic phase (S-phase) ratio of cardiac myocytes of spontaneously hypertensive rats (SHR) utilizing monoclonal antibody to 5-bromo 2' deoxyuridine (BrdU), a halogen derivative of thymidine. BrdU was administered intraperitoneally to SHR and Wistar Kyoto rats at 66.7 mg/kg/day for 3 consecutive days. The rats were sacrificed 1 week after the first injection of BrdU. Using anti-BrdU antibody, myocardial tissue was stained by the avidin biotinylated peroxidase complex method. We assessed the ability of the nuclei to synthesize DNA. The percentage of BrdU-labeled myocytes was higher in SHR than in control rats at 9 weeks. The hyperplastic phase of heart growth in rats was presumed to occur about 3 weeks after birth. From these results, the ability of the myocardial cell to synthesize DNA is probably enhanced under the load of high blood pressure in the early hypertrophic phase following hyperplasia. PMID- 8510316 TI - Aortic valvular disease and right coronary artery stenosis induced by mediastinal irradiation--report of a case. AB - This report presents a case of aortic valvular dysfunction and right coronary artery disease following radiation therapy on the mediastinum. A 61-year-old woman had received mediastinal radiation for the treatment of right mammary cancer 20 years previously. She developed symptoms of congestive heart failure 6 months ago. The patient was found to have aortic valvular dysfunction and proximal stenosis of the right coronary artery. Surgical aortic valve replacement improved cardiac status, and vasodilator treatment reduced ischemia due to right coronary artery stenosis. PMID- 8510315 TI - Ca2+ transients and cell shortening in diabetic rat ventricular myocytes. AB - To investigate the role of abnormal Ca2+ metabolism in the diminished contractile function of diabetic myocardium, we measured the Ca2+ transients and cell contraction of diabetic rat myocytes. Isolated diabetic (8 weeks after 40 mg/kg streptozotocin, i.v.) and normal myocytes were loaded with acetoxymethyl ester of indo-1 (indo-1/AM). Ca2+ transients and cell circumferential shortening were measured simultaneously, using high temporal resolution video image analysis. The diastolic base and systolic peak of Ca2+ transients were significantly lower in diabetic myocytes than in normal myocytes (peak ratios: 0.49 +/- 0.02 vs 0.56 +/- 0.01, p < 0.05; base ratios: 0.43 +/- 0.01 vs 0.48 +/- 0.01, p < 0.01, Mean +/- SE). The cell circumferential shortening of diabetic myocytes was also significantly lower than that of normal myocytes (2.9 +/- 0.3% vs 5.2 +/- 0.9%, p < 0.05). Although isoproterenol (10(-8) and 10(-7) M) increased the peak of Ca2+ transients in both diabetic and normal myocytes, the peak value of Ca2+ transients in the diabetic group was significantly lower than that in the normal group. The decreased Ca2+ transients may be responsible for the decreased contractile function in diabetic myocardium. PMID- 8510317 TI - Coronary spasm in two sisters. AB - Coronary spasm was observed in two sisters. Neither of them had significant atheromatous stenosis in the coronary arteries. The 41-year-old elder sister presented with resting morning angina. The stress electrocardiogram showed marked depression of the ST-segment in precordial leads. Diffuse vasospasm in the left anterior descending artery was induced by the intracoronary administration of acetylcholine. The 38-year-old younger sister suffered from acute inferior myocardial infarction after taking methylergonovine following an abortion. Emergent coronary angiography disclosed a thrombus in the proximal right coronary artery which was dissolved with intracoronary administration of urokinase. There was no residual stenosis in the culprit vessel. Although the sisters do have risk factors for coronary spasm, an inherited factor may contribute to the mechanism of the spasm. PMID- 8510318 TI - [In vitro MIC break point for appropriate clinical use of antibiotic]. AB - In vitro antimicrobial susceptibility tests can play an essential role in clinical management of infectious diseases, and in vitro MIC break point is important in choice of antibiotic. Standardization of method for measuring MIC is necessary, if break points are to be fixed internationally. However, it is difficult to settle on uniform international break points, since standard doses of antibiotics and the preferred routes of administration differ in different parts of the world. With respect to in vitro MIC break points, the NCCLS system is used in the U.S.A., and in Japan, Showa disc system and the NCCLS system are both used. In Europe 6 different systems are utilized (BSAC, DIN, SFM, SIR, NCCLS, and WRG). There is a certain degree of similarity between different concentration values used to define break points in these systems. In general, however, the BSAC and DIN systems recommend lower break points and the NCCLS and SFM systems higher break points. The MIC values of the break points, +3 and +2 categories of Showa 4 category classification system (+3, +2, +, -) used in Japan, are similar to those of the BSAC system. Higher ratio of positive responses to bactericidal antibiotic therapies have been reported when ratios of peak concentrations of drugs in plasma/in vitro MIC are increased, and maximum responses are obtained when the ratio reaches about 8 in cases with aminoglycosides and beta-lactams. In neutropenic compromised patients, drug concentrations with ratios higher than 8 to 10 may be required to treat infections. Drug availabilities are different depending on drugs and sites of infections. Susceptibility patterns to antibiotics are also quite different with different organisms. From the evidence presented above, a multiple (at least 2, low and high) sensitivity MIC break point system appears to be more appropriate than a single sensitivity MIC break point system to cope with various infections. Multiplicity of break points should depend on types of organisms, antibiotic availabilities at sites of infections, and specific factors in patients. Pharmacokinetic data on antibiotics must be more precisely taken into account with respect to the diversity of dosages, and especially effective antibiotic concentrations at sites of infections. PMID- 8510319 TI - [Enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam in combination against methicillin-susceptible and -resistant Staphylococcus aureus studied using checkerboard MIC method and disc diffusion method with discs containing both drugs]. AB - Antimicrobial activities of cefmetazole (CMZ) and cefotiam (CTM) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin susceptible strains and 47 methicillin-resistant strains) by the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CTM individually against 9 methicillin susceptible strains (MSSA) were 0.78 approximately 1.56 micrograms and 0.39 approximately 0.78 micrograms/ml without 4% NaCl, and 1.56 approximately 3.13 micrograms/ml and 0.78 approximately 1.56 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CTM, MICs of CMZ and CTM against these MSSA decreased to 0.20 approximately 0.39 micrograms/ml and 0.20 micrograms/ml without 4% NaCl, and 0.20 approximately 0.78 micrograms/ml and 0.10 approximately 0.78 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.313 to 0.628. FIC indexes < or = 0.5 were observed against 7 out of 9 strains. MICs of CMZ and CTM individually against 47 methicillin-resistant strains (MRSA) were 6.25 approximately 100 micrograms/ml and 3.13 approximately 800 micrograms/ml in the absence of 4% NaCl, and 6.25 approximately 100 micrograms/ml and 50 approximately greater than 800 micrograms/ml in the presence of 4% NaCl, respectively. In combination of CMZ and CTM, MICs of these drugs against MRSA were reduced to 0.20 approximately 25 micrograms/ml without 4% NaCl and 0.39 approximately 25 micrograms/ml and 3.13 approximately 200 micrograms/ml with 4% NaCl, respectively. The strains studied showed minimum FIC indexes of 0.02 to 0.5 either with 4% NaCl or not. By the disc diffusion method, between CMZ disc and CTM disc a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone than discs containing the equivalent amount of CMZ or CTM alone. These in vitro observations reported here suggest that the use of CMZ and CTM in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection. Prophylactic use of CMZ and CTM in combination for surgical infection would be also more effective than the use of these drugs individually. The synergistic enhancement of antimicrobial activity of CMZ and CTM in combination was assessed using discs containing various amounts of these drugs at various ratios. In this investigation, discs containing CMZ/CTM (20 micrograms/10 micrograms) was selected. Using discs containing CMZ/CTM (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CTM in combination.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510320 TI - [Antibacterial activities of arbekacin against recently isolated methicillin resistant Staphylococcus aureus (I)]. AB - Against 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1990 to 1991, minimum inhibitory concentrations (MICs) of a total of 15 antibacterial agents including arbekacin (ABK) were determined. In addition coagulase types of the tested strains were determined and classified according on their origins. 1. Among the coagulase types of 200 strains, type II were 63.5%, type IV 18.5%, type VII 11.0% and the other types 7.0%. Type II strains were prevailing among those isolated from the respiratory tract specimens and type IV among those from the surgical specimens. These results were in agreement with other recent reports including our previous ones. 2. The MIC50 of methicillin, 6 cephalosporins (CEPs), imipenem, fosfomycin (FOM), gentamicin, tobramycin and clindamycin for 200 strains ranged from 50 to > 100 micrograms/ml. On the other hand, MIC50 and MIC90 of ABK, minocycline (MINO) and vancomycin (VCM) were 0.78 and 3.13 micrograms/ml for ABK, 0.39 and 50 micrograms/ml for MINO, and 0.78 and 1.56 micrograms/ml for VCM. 3. The MIC90 of ABK against coagulase type IV strains was rather high, 12.5 micrograms/ml. However, the strains inhibited by 6.25 to 12.5 micrograms/ml of ABK were isolated even in our studies performed in 1986, 1988 and 1989. Further studies are therefore required to confirm whether appearance of these strains used in the present study inhibited at relatively high concentrations of ABK is due to the use of ABK. 4. It is reported that, at present, most of the MRSAs spreading in Japan are acceleratedly acquiring resistance to many drugs, and especially, they are developing high resistance against beta-lactams. ABK showed potent antibacterial activities even against these strains. Since ABK has been shown to display potent activities against MRSA in combination with beta-lactams or FOM, we believe ABK is one of the useful aminoglycoside antibiotics for the treatment of MRSA infections. PMID- 8510321 TI - Effects of 3 aminoglycoside antibiotics (kanamycin, gentamicin and fradiomycin) on the thrombin-induced aggregation and intracellular Ca2+ mobilization of human platelets. AB - This study was aimed at determining whether the thrombin (TRB)-induced aggregation and intracellular free Ca2+ ([Ca(2+)]i) mobilization of fura-2-loaded human platelets would be affected by aminoglycoside antibiotics (AGs), i.e., kanamycin (KM), gentamicin (GM) and fradiomycin (FRM) with 4, 5 and 6 amino groups in their molecules, respectively. We used pH-adjusted solution of AGs, since the TRB-induced aggregation and [Ca(2+)]i mobilization are pH-dependent. TRB (0.1 U/ml) induced aggregation in the presence of 1 mM external Ca2+ but did not in the absence of external Ca2+. The 3 AGs reduced the TRB-induced aggregation and the antiaggregating potencies were in the order FRM = GM > KM. TRB-induced [Ca(2+)]i elevation in the presence of external Ca2+ was 3 times higher than in the absence of external Ca2+ and the 3 AGs concentration dependently reduced the TRB-induced [Ca(2+)]i elevation in the absence of external Ca2+ as well as in its presence, and the potency order was FRM > GM > KM. The IC50 of GM or KM was higher in the absence of external Ca2+ than in its presence, while the IC50 of FRM was scarcely affected by the deprivation of external Ca2+. These results suggest that the reducing potency of the 3 AGs in the TRB-induced aggregation and [Ca(2+)]i mobilization of human platelets is based on the number of amino groups. Furthermore, it is suggested that GM and KM predominantly reduce the Ca2+ influx rather than the intracellular Ca2+ release but FRM is equieffective in decreasing both of them. PMID- 8510322 TI - [A combined sulbactam/cefoperazone and amikacin therapy for the treatment of infections complicated with hematological diseases]. AB - Eighty-six patients with infections associated with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ) and amikacin (AMK). Among 71 evaluable cases, 30 cases had acute non-lymphocytic leukemia, 3 acute lymphoblastic leukemia, 25 malignant lymphoma, and 7 myelodysplastic syndrome as underlying diseases. Excellent responses were obtained in 33 cases (46.5%) and good responses in 14 cases (19.7%), with an overall efficacy rate of 66.2%. The efficacy rate among cases with suspected sepsis was 72.5%. This treatment was also effective in 69.2% of cases in which neutrophil counts were less than 500/microliter through the course of administration. The eradication rate was 83.3% among 6 strains in which Gram-negative rods were detected. Side effects were minimum; skin rash in 1 case, slight elevation of APTT in 3 and slight elevation of total bilirubin in 1. Thus, this combination antibacterial chemotherapy is an effective and safe regimen for the treatment of severe infections in patients with hematological disorders. PMID- 8510323 TI - [Chemotherapy with imipenem/cilastatin for severe infections accompanied by malignant hematological disorders]. AB - The clinical and bacteriological efficacy of imipenem/cilastatin (IPM/CS) was evaluated in 30 cases of serious infections associated with hematological malignancies. 1. Among 28 evaluable cases, excellent efficacy was obtained in 6 cases and good effectiveness in 10 cases, resulting in a high clinical efficacy rate (57.1%). The clinical effectiveness of IPM/CS was not dependent on neutrophil count in peripheral blood. A 53.8% efficacy rate was observed in 26 cases which had received pretreatment with other antibiotics. 2. Antibacterial activities of IPM/CS have so far been evaluated against organisms isolated in 20 of 28 cases: 2 strains of coagulase-negative Staphylococcus, 2 strains of methicillin-resistant Staphylococcus aureus, 2 strains of Enterococcus faecalis, 9 strains of Enterobacter cloacae, and 8 other strains. 3. Among 3 evaluable cases treated with IPM/CS alone, response was good in 1 case. Among 25 patients receiving IPM/CS in combination with an aminoglycoside or a penicillin, the efficacy rate was 60%. 4. Five patients had IPM/CS-related adverse events; nausea and vomiting in 2 cases, seizures in 1 case, small increases in GOT and GPT in 2 cases, and the appearance of casts in urine sediment in 1 case. These patients, however, tolerated the complete course of therapy with IPM/CS except the 2 cases with nausea and vomiting. These results indicate that chemotherapy with IPM/CS is effective for the treatment of severe infectious diseases accompanied by hematological disorders. PMID- 8510324 TI - Bacterial flora detected in the uterine endometrial cavity of normal puerperae on the puerperal first day and on the puerperal fifth day after incidental use of cefpodoxime proxetil. AB - In Japan, oral antimicrobial agents are prophylactically used with oxytocics after normal delivery to prevent puerperal infections. The present study was designed to investigate bacterial floras in the endometrial cavity immediately after normal delivery and the effect of prophylactic use of anti-microbial agents on those floras. Sixty-six puerperae who underwent uneventful courses of pregnancy and delivery were subjected for this study. Intrauterine contents were collected on the first day and the fifth day of the puerperium and submitted to microbiological examinations. Cefpodoxime proxetil (CPDX-PR) was orally given to the puerperae for prophylaxis for 5 days after the initial sampling. On the puerperal first day, a total of 98 strains (71 strains of aerobic bacteria, 27 strains of anaerobic bacteria) was detected in the uteri of the 66 subjects. The incidences of aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria were 59.2%, 12.2%, 27.6% of the 98 strains, respectively. On the puerperal fifth day, a total of 82 strains (51 strains of aerobic bacteria and 31 strains of anaerobic bacteria) were detected in the uteri of the 66 subjects. The incidences of aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria were 52.5%, 8.6% and 37.7% of 82 strains, respectively. PMID- 8510325 TI - [Mechanism of thrombolytic enzymes]. AB - Thrombolytic enzymes belong to plasminogen activator (PA) in blood fibrinolysis and love been used for the efficient thrombolysis is achieved by the administration of PA which has high affinity for fibrin and induces plasminogen activation on the fibrin surface. PA with lower affinity for fibrin can activate plasminogen in circulating plasma, which causes bleeding tendency. At present, 11 PAs which are available for clinical usage or under investigation, are classified into two types: direct-type PA and indirect-type PA. The former which cleaved plasminogen directly and produces plasmin, includes urokinase-type PA, tissue type PA, single-chain u-PA, bat PA, mutant PA, hybrid PA, IgG carrying PA and bispecific monoclonal antibody. The latter has no biological function by itself and expresses PA activity after forming a complex with plasminogen. This group includes streptokinase, anisoylated plasminogen streptokinase activator complex and staphylokinase. The PA activity of staphylokinase/plasminogen complex is inhibited by alpha 2-plasmin inhibitor, but can be expressed on the fibrin surface. Thus, PA activity of this complex is hardly observed in plasma. These feature of staphylokinase resembles to tissue-type PA. PMID- 8510326 TI - [Current status of transfusion-transmitted infection]. AB - Recently transfusion-transmitted infections (TTI) have been decreased remarkably. Especially nonA, nonB posttransfusion hepatitis (PTH) has reduced to one third by introducing anti-HCV (C100-3) antibody screening. HCV-PTH will be lowered more with screening by the 2nd generation reagent of HCV. None of cases with HIV infection by transfusion has been reported since introduction of anti-HIV antibody screening, but we have to watch out it, due to rapid increase of heterosexual infection of HIV during this one year in Japan. Voluntary blood donors should warrant blood safety by their own responsibility. We have no cases with malaria by transfusion for these several years. There are no reported cases with Chagas' disease in Japan, but increase of international immigrations will be potential to introduce these infections by transfusion into Japan. Recently TTI by bacteria-contaminated blood have been very rare owing to technical improvement of blood-drawing. However, platelet concentrates stored at 22 degrees C for 3-5 days and red cell products stored at 4 degrees C for 35-42 days have presented new problems concerning bacterial contamination. We have to consider these problems concerning bacterial contamination. PMID- 8510327 TI - [Mechanisms of multiple myeloma cell growth]. AB - The mechanism of human multiple myeloma cell growth was studied utilizing eleven myeloma cell lines established in vitro or in vivo (Scid mouse). Four bone marrow derived cell lines grew dependently on IL-6 or bone marrow stromal cells. Seven extramedullary lesion derived cell lines grew spontaneously and additively proliferated in response to IL-6. All cell lines expressed the IL-6 receptor (IL 6R) and IL-6RmRNA, but none expressed IL-6mRNA. No IL-6 activity was detected in the myeloma cell culture supernatant. Both the anti-IL-6 antibody and anti-IL-6R antibody neutralized IL-6-induced proliferation, but did not inhibit spontaneous proliferation of extramedullary lesion derived cell lines. While establishing cell lines, it was found that the proliferating fraction was primarily included in a fraction which was non-adherent to stromal cells and composed of undifferentiated plasmablasts. Undifferentiated plasmablasts proliferated in response to IL-6, in contrast to the adherent, mature form of myeloma cells which did not proliferate in response to IL-6. Innoculation of myeloma cells into Scid mice induced subcutaneous tumor formation. These tumors were composed of undifferentiated plasmablasts, which also proliferated in response to IL-6. These results imply that the growth of bone marrow derived myeloma cell lines are dependent on the IL-6 paracrine mechanism and that the growth of extramedullary lesion derived cell lines primarily autonomous and additively dependent on the IL 6 paracrine mechanism. PMID- 8510328 TI - [Growth characteristics of a human myeloma cell line transfected with IL-6 cDNA]. AB - It remains to be clarified whether IL-6 acts on the growth of human myeloma cells by an autocrine or paracrine mechanism. Even in established myeloma cell lines, the autocrine growth by IL-6 appears unusual. In the present study, we deviced a model of IL-6 autocrine growth in vitro by transfecting IL-6 cDNA into a human myeloma cell line that had a proliferative response to IL-6 but did not produce IL-6. After IL-6 transfection, the cells (S6B45) proliferated in culture media without IL-6. IL-6 production by S6B45 was demonstrated both at protein and mRNA level. The growth of S6B45 was definitely inhibited by anti-IL-6 (MH166) or anti IL-6 receptor (PM1) monoclonal antibodies. Furthermore, S6B45 was successfully transplanted to nude mice. The transplanted tumor growth was clearly inhibited by the administration of MH166 or PM1 to the mice. The in vivo antitumor activity of these antibodies suggest a new therapeutic strategy against tumors that proliferate by an autocrine mechanism through a cytokine such as IL-6. PMID- 8510329 TI - [Multiple myeloma and adhesion molecules]. AB - The physiological role of fibronectin (FN) on the human plasma cells were examined using three PC cell lines, FR4ds, OPM1 and OPM1ds. FR4ds was reactive with anti-VLA-alpha 4 and anti-alpha 5. In contrast, OPM1 and OPM1ds were not reactive with anti-VLA-alpha 5. FN induced spreading in FR4ds and OPM1ds. Albumin blocked these spreadings. FR4ds with mature plasma cell phenotype of alpha 4+ and alpha 5+ was more sensitive for FN than OPM1 and OPM1ds with immature phenotype of alpha 4+ and alpha 5-. Spreading cells proliferated more than floating cells. All these cell lines showed chemotaxis toward FN. alpha 5+ FR4ds was more sensitive for FN than OPM1 and OPM1ds with alpha 5- phenotype. These new abilities of PC of spreading and chemotaxis we found are summarized to be an affinity to organs. It is likely that alpha 4+ and alpha 5- PC with low affinity to organs are stored in peripheral blood as a result. We examined the chemotaxtic activity of myeloma cells in bone marrow and these in pleural effusions in a patient with multiple myeloma. These cells in pleural effusions showed more chemotaxic activity than these in bone marrow. FN induced growth, production of Ig, and motility of PC, which resulted in the augmentation of humoral immunity. PMID- 8510330 TI - [The wide variations of the clinical behavior and prognosis in multiple myeloma]. AB - The clinical course of multiple myeloma (MM), ranging from relatively asymptomatic form to frankly aggressive neoplasia, is more variable than that of other hematologic malignancies. The nature of tumor cells and/or the secondary effects of malignancy as anemia, hypercalcemia, and renal failure have shown to correlate with clinical behavior of MM. Prognostic variables include age, degree of anemia, morphologic subtypes, serum creatinine and calcium levels, Bence Jones proteinuria, plasma cell LI%, beta 2MG level, nucleolus-associated J chains and other laboratory prognostic factors. The plasma cell LI% is the most reliable predictor of survival. Analysis of the presenting features and the clinical characteristics indicates that there are several variants of MM with a poor prognosis, including juvenile myeloma, plasma cell leukemia, aggressive myeloma, high LDH myeloma, J chain myeloma, and amylase-producing myeloma. Four relapsing patterns have been pointed out. The appearance of an additional M-component (mutation escape) suggests the terminal or advanced stage of illness. A new lambda-type M-component can be found in patients with kappa-type myeloma. The prognostic significance of Bence Jones escape varies for different stage of illness. Bence Jones escape is an important predictor of the development of overt MM in patients with smoldering MM. The need for clearly established prognostic criteria is imperative for the choice of correct therapeutic strategies. PMID- 8510331 TI - [Clinical features and status in multiple myeloma]. AB - Quantitation of peripheral circulating myeloma cell precursors, problems on serum beta 2-microglobulin value which is a prognostic factor in myeloma, and prognostic factors associated with long-term survival in our Japanese myeloma patients are described. Peripheral blood mononuclear cells were cultured in vitro in the presence of various recombinant cytokines and differentiated to plasma cells to quantify peripheral circulating myeloma cell precursors. It has speculated that the variation in the number of myeloma cell precursors in peripheral blood could be used as a parameter of the efficacy of chemotherapy in patients with myeloma. Serum beta 2-microglobulin value increased with age and under alpha-interferon therapy in myeloma, even if M protein decreased, suggesting that its value should be carefully monitored when evaluating the response to alpha-interferon and other chemotherapeutic agents. Of 1,119 Japanese patients with symptomatic myeloma who were newly diagnosed at 16 institutions of the Japan Myeloma Study Group between 1965 and 1981, 38 (3.4%) patients survived for more than 10 years. In comparison with 121 patients who died within 10 years in our institution, younger age, low and intermediate tumor mass, lower plasmacytosis, higher percentages of granulocytes and erythroblasts in bone marrow, and subtype classified as mature or intermediate were strongly correlated with long-term survival. PMID- 8510333 TI - [New protocols for myeloma chemotherapy plus IFN alpha]. AB - In two consecutive studies of a pilot study and a multicenter trial 16 patients and 61 patients, respectively, with multiple myeloma were treated with the combination chemotherapy (CMVM regimen; the same intermittent high dose dexamethasone as in VAD regimen, MCNU bolus injection of 1.2mg/m2 on day 1, melphalan 12mg/day on days 1-6) plus IFN alpha (HLBI 300MU every day or two) to assess the efficacy and the toxicity of this protocol. Both studies were achieved in the same regimen except for initial 12 days administration of IFN alpha in the multicenter trial. The treatment was repeated 3 times every 6-8 weeks. Complete remission (CR) in which serum and urine M protein disappeared and myeloma cells in bone marrow were eradicated was obtained in 6 in 16 patients (37.5%) in the pilot study and 16 in 61 patients (26.2%) in the multicenter trial. CR plus PR was 68.8% and 68.9% in two studies. The achievement of CR in such high proportion of patients may exhibit a significant advance in the myeloma therapy. PMID- 8510332 TI - [Recent therapy for refractory myeloma]. AB - There are only 3.3% of patients with multiple myeloma in Japan Myeloma Study Group who have lived longer than ten years. Features associated with long survival include responded well to simple treatment such as melphalan or cyclophosphamide and prednisone, short duration of treated time with long activity and prolonged unmaintained remissions. High-dose melphalan therapy, VAD chemotherapy and MCNU-VP16-melphalan combination were tried for patients relapsed with alkylating agents and the result were reported. Bone marrow transplantation and cytokine therapy for myeloma will be discussed. PMID- 8510334 TI - [Treatment of elderly patients with chronic idiopathic thrombocytopenic purpura]. AB - We report a therapeutic protocol for elderly patients with chronic idiopathic thrombocytopenic purpura (ITP) and related conditions. Twelve chronic ITP patients over 60 years of age (elderly group), and 40, 59 years old or less (young group) were evaluated in this study. The therapeutic protocol for ITP, proposed by the Japanese Idiopathic Disease of Hematopoietic Organ Research Committee, was modified for the elderly (group) as follows: the initial dosage of prednisolone was reduced by half and danazol therapy was selected in cases in which splenectomy was impossible. Platelet counts and PAIgG showed no significant difference between the two groups. All 12 elderly patients were initially treated with prednisolone, and five patients responded to it. Among the seven non responders, four patients underwent splenectomy, and the three three others (non splenectomized patients) were treated with danazol. Platelet counts were maintained over 150 x 10(3)/microliters in eleven patients except one splenectomized patient. The outcome in the elderly ITP group was better than in the young group. PMID- 8510335 TI - [Determination of the standard level of serum erythropoietin in relation to hemoglobin concentration]. AB - Serum erythropoietin (EP) concentration was measured by the recombinant EP-based radioimmunoassay and was examined to standardize the hemoglobin (Hb) related level of 144 normal control and 56 patients with iron deficiency anemia and hemolytic anemia excluding paroxysmal nocturnal hemoglobinuria. The standardization was achieved by logarithmic regression of the EP titier on Hb either by the two-phase linear form or by the third degree sigmoid form at a 95% confidence limit for each regression. The third degree regression was found to be preferable from the view point of both statistics and the negative feedback mechanism. The average and scattering of the deviation from the standard level thus determined of the disease groups indicated that the EP level is: (1) 12 fold higher than the standard level in 42 aplastic anemias (the most in excess and a few in standard). (2) three fold higher than that in 27 myelodysplastic syndromes (relatively higher dispersed state). (3) 29% of the standard level in 33 anemias associated with chronic renal failure (deficient state). (4) 105% of the extrapolated standard level in 22 polycythemia veras (standard state). The standardization of Hb-related Ep titer may provide new pathophysiological approaches in a variety of hematopoietic disorders. PMID- 8510336 TI - [Proliferation of micromegakaryocytes in acute myelocytic leukemia associated with 5 q- as the sole karyotypic abnormality]. AB - The authors report a de novo AML (M2) patient associated with 5q- as the sole karyotypic abnormality. A 76-year-old woman was referred to our hospital because of anemia and leukocytosis. On examination a neck lymph node was enlarged, but neither the liver nor the spleen could be palpated. The hemoglobin level was 7.1g/dl, the mean corpuscular volume 102fl and the white-cell count was 256.1 x 10(3)/microliters with 87% blast cells. The platelet count was 10.9 x 10(4)/microliters. The bone marrow was hypercellular with 79.8% blast cells and showed dysmegakaryocytopoietic features (hypolobulation, multiple separated nuclei and micromegakaryocytes). Blast cells gave a positive reaction for peroxidase and alpha NB esterase which was not blocked by NaF. The diagnosis of AML (M2) was made but she died before chemotherapy. Autopsy revealed general hemorrhagic tendency and leukemic cell infiltration. Chromosome analysis of the bone marrow showed 46,XX,del(5) (q13q31). Electron micrographs revealed increase of micromegakaryocytes as small as myelocytes and aggregation of demarcation membranes in some megakaryocytes. This may suggest that some molecular changes, instead of karyotypic evolution, contributed to a leukemic transition from the 5q syndrome to AML with 5q- as the sole abnormality. PMID- 8510337 TI - [Transient pure red cell aplasia in an adult with acute parvovirus B19 infection: observation of PVB19 DNA by polymerase chain reaction, viral antibody and erythroid cells in the bone marrow]. AB - A 35-year-old female was referred to our hospital for fever and anemia. Physical examination was unremarkable. Complete blood count revealed microcytic hypochromic anemia and reticulocytopenia. The bone marrow cellularity was normal. Some giant pronormoblasts were seen but other erythroid cells were absent. No stainable iron was seen. Parvovirus B19 (PVB19) DNA was detectable by polymerase chain reaction. Anti-PVB19 IgM-antibody was also positive in the serum on admission. Antibodies against rubella, measles, mumps, EB virus and HBs were negative and HBs antigen was also negative. Thus the diagnosis of iron deficiency anemia complicated with pure red cell aplasia secondary to PVB19 infection was made. The PVB19 DNA was still positive on days 6 and 11, suggesting that PVB19 virus persists as long as 3 weeks after the onset of PVB19 infection. However, the erythroid cells had recovered by day 6 after admission suggesting that the development of IgM antibody successfully protected the erythroid cells from infection by the residual PVB19. Hence, careful observation for PVB19 DNA and the antibody may be necessary if immunodeficient patients developed anemia of unknown etiology. PMID- 8510338 TI - [A case of vivax malaria with thrombocytopenia suggesting immunological mechanisms]. AB - Recently, it has been shown that the thrombocytopenia that complicates some malarial infections is caused by immune mechanisms. We report a case of malaria associated with thrombocytopenia and increased platelet-associated IgG (PAIgG). In this case, anti-malarial therapy reduced the level of PAIgG to normal levels in association with normalization of the platelet count. This case suggests the immunological mechanisms of thrombocytopenia in malaria. PMID- 8510339 TI - [Human parvovirus B19-induced aplastic crisis in an elderly man with intestinal hemorrhage]. AB - An elderly man with an intestinal hemorrhage from bowel diverticulosis developed human parvovirus B19-induced aplastic crisis. A 71-year-old man noticed occasional tarry stools and at the same time showed fever, arthralgia and severe anemia. Blood counts revealed Hgb 5.3g/dl, reticulocytes 0%, and WBC 1,900/microliters. Bone marrow examination showed hypocellular marrow with rare erythroid precursors (4.8%). A few giant proerythroblasts were found in the bone marrow smears. A diagnosis of parvovirus B19 infection was made because of detection of B19-specific IgM and IgG antibodies. Parvovirus B19 infection should be carefully checked for in patients with hemorrhage as well as those with hemolysis. PMID- 8510340 TI - [Analysis of measuring conditions of surface electromyogram using mathematical model]. AB - To study the measuring conditions of surface electromyogram for work analysis in the field of industrial health, the effect of electrode fixation, electrode distance and electrode-muscle distance were studied using a mathematical model. The results were as follows; 1) The output waveforms of two electrode fixed models, i.e., parallel-fixed model (two electrodes were fixed in parallel to the direction of the muscle fibers) and transverse-fixed model (two electrodes were fixed in transverse to the direction of the muscle fibers) were compared. The maximum output and rectified integrated output of the parallel-fixed model were 2.59 times and 1.2-1.5 times larger than those of transverse-fixed model, respectively. The high output area of the parallel-fixed model was only one round area, but the areas of transverse-fixed model were four round areas which were wider than the area of the parallel-fixed model. The rectified integrated output of the parallel-fixed model was more affected by the location of neuro-muscular junction than that of transverse-fixed model when the electrodes were fixed near the neuro-muscular junction. 2) The rectified integrated output increased by electrode distance, and the changing rate of the rectified integrated output by electrode distance was particularly large when the electrode distance was shorter than 2 cm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510341 TI - [Usefulness of delta-aminolevulinic acid in blood as an indicator of lead exposure]. AB - The concentration of delta-aminolevulinic acid in blood (ALA-B) was determined using high performance liquid chromatography (HPLC). To improve the chromatographic separation and the recovery rate of ALA determination in blood, acetate buffer was used in the reaction mixture of fluorescence derivatization. The detection limit of ALA-B was ca. 2 micrograms/l at signal to noise ratio of 5, and the analytical recovery was 102.0 +/- 4.10% (mean +/- SD), when 50 micrograms/l of ALA was added to 7 blood samples (ALA-B levels: 6.5-103.0 micrograms/l). ALA-B levels in control subjects (n = 19) were 5.3 +/- 1.4 micrograms/l (mean +/- SD) and those in 52 lead workers (blood lead levels (Pb B): 2.4-86.2 micrograms/dl) were 15.4 +/- 12.2 micrograms/l (range: 3.1-137.3 micrograms/l). Standard curve of ALA was linear over a wide range, at least up to 400 micrograms/l. In the workers, the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. delta-aminolevulinic acid dehydratase activity (ALA-D) were higher than those of urinary concentration of ALA vs. Pb-B and that vs. ALA-D, especially in the moderate Pb-B level (less than 40 micrograms/dl, n = 35). Unless the urinary concentrations of ALA were not corrected, significant correlation could not be found between Pb-B and urinary ALA in the workers moderately exposed to lead, and the correlation coefficient between urinary ALA and ALA-D was -0.354, while the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. ALA-D were 0.739 and -0.746, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510342 TI - [Effects of repetitive light work on muscle pressure pain threshold and EMG]. PMID- 8510343 TI - [Changes in DNA synthesis and glutathione contents of primary cultured hepatocytes from the methylmercury treated rat]. PMID- 8510344 TI - [Protective effects of intracellular glutathione against methylmercury cytotoxicity in primary cultured rat hepatocytes]. PMID- 8510345 TI - [Improvement of urinary delta-aminolevulinic acid determination by HPLC fluorometry using pre-column derivatization]. PMID- 8510346 TI - [Comparison of life style and health practices between the subjects of occupational health services and those of community health services]. AB - A questionnaire was mailed to a total of 3,889 residents 40, 45, 50, 55, 60, and 65 years of age living in 11 municipalities of Hida district, Gifu Prefecture, Japan, to inquire about their life style and health practices. Of the 3,889 residents, 2,919 (75.1%) responded to the questionnaire. They were divided into two groups for comparison; the subjects of occupational health services and those of community health services. The subjects of occupational health services at ages 40-55 showed lighter daily physical activity level than those of community health services. However, the subjects at ages 60 and 65 showed equally heavy daily physical activity level in two groups, which indicates that the subjects of occupational health services aged 60 and 65 years are engaged in heavier job at worksite and home. The prevalence of self-rated stress tended to be higher in the subjects of occupational health services. The mean health practice scores tended to be higher for the subjects of occupational health services than for those of community health services at ages 40-55. The percentage of people who had examinations for circulatory diseases were higher among the subjects of occupational health services at ages 40-60 compared with those for the subjects of community health services. Many of the subjects of occupational health services receiving an examination for stomach cancer had obtained the examination service at municipalities provided by local governments. The subjects of occupational health services generally showed superior attitudes toward health care, which suggests that health management for the former is more easily approached than the latter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510347 TI - [Occupational diseases caused by exposure to sensitizing metals]. AB - Diseases caused by occupational exposure to sensitizing metals including platinum (Pt), rhodium (Rh), nickel (Ni), chromium (Cr), cobalt (Co), gold (Au), mercury (Hg), zirconium (Zr) and beryllium (Be) are reviewed. Allergic reactions induced by the metals are described according to the classification by Coombs and Gell. Metals with unproven sensitizing potential are not discussed if reports on these are either very rare or devoid of convincing evidence for allergic involvement. The sensitizing metals are haptens which are not themselves able to act as antigens. There is evidence that combination of the metals with circulating or tissue protein gives rise to new antigens. An alternative hypothesis is that these metals interfere with the antigen recognition step of the immune response. Immunomodulatory effects or immunotoxicity of the metals may be also involved in metal-induced hypersensitivity. Occupational exposure to Pt, Rh, Ni, Cr, and Co causes allergic asthma via type I allergic reaction in which serum from affected individuals shows specific IgE antibodies against mental-human serum albumin conjugates. Some rheumatoid arthritis patients treated with gold salt therapy develop glomerulonephritis, thrombocytopenia, or agranulocytosis, which arise from type II and/or type III allergic reactions. Occupational exposure to mercury causes glomerulonephritis in which involvement of type III reaction is suggested. Type IV hypersensitivity reaction of the skin also takes place following exposure to the metals: allergic contact dermatitis is evoked by exposure to Ni, Cr, Co, Rh, and Hg; cutaneous granuloma is formed by contact with Zr and Be. Be is also a sensitizer of the lungs, resulting in granulomatous disease. Diagnosis of metal induced allergic diseases is made on the basis of allergological tests with metal antigens including skin tests, radioallergosorbent test for specific antibody, lymphocyte transformation test, macrophage migration inhibition test, and provocation test. Atopy is a predisposing factor and smoking is a risk factor for developing metal-induced asthma. Evidence for genetic factors in the development of metal contact dermatitis is conflicting, although animal models implicate genetic factors in skin sensitization with some metals and respiratory sensitization with Be. Skin irritation, forearm injury, complication with atopic dermatitis and concomitant sensitization to other agents are determinants for prognosis of the dermatitis. Epidemiological reports of occupational diseases from allergic reactions to metals in industries are reviewed with respect to prevalence and allergic manifestations. There is a report on a clinical trial of hyposensitization with Pt in a platinum asthma patient. Predictive methods for evaluating sensitization potential of metals have been developed and new methods, which quantify potential more objectively, are sought. PMID- 8510349 TI - [Effects of lifestyle on hematologic parameters; I. Analysis of hematologic data in association with smoking habit and age]. AB - The effects of smoking and age on the results of hematologic tests were determined in a group of 429 healthy male workers. The results obtained were as follows: 1) The values of total leucocyte count (x10(9)/l), neutrophil count (x10(9)/l), lymphocyte count (x10(9)/l), monocyte count (x10(9)/l), hemoglobin (g/l), hematocrit, mean corpuscular volume (MCV; fl), mean corpuscular hemoglobin (MCH; pg), and mean corpuscular hemoglobin concentration (MCHC; g/dl) in current smokers were significantly higher than those in non-smokers. 2) Total leucocyte counts and neutrophil counts significantly increased with the number of cigarettes smoked per day in current smokers. 3) Total leucocyte counts, neutrophil counts, and lymphocyte counts significantly increased with Brinkman Index (B.I.) in current smokers. 4) The increase of age was significantly associated with the decrease of erythrocyte counts and the increase of MCV in both current smokers and non-smokers. PMID- 8510348 TI - [Health care of work stress: a review]. AB - In order to clarify the health effects of work stress and possible strategy for its prevention and treatment, we reviewed the literature on work stress as follows: 1) Review was made on 12 major psychosocial work stressors, 4 acute reactions to stress, disease outcome of work stress, measurement methods of those variables, and theoretical models of work stress. 2) Epidemiological studies of the effects of work stressors on cardiovascular diseases, psychological distress and mental disorders in Japan were reviewed. Also, work stress in specific occupations such as software engineers, nurses and female researchers was reviewed. 3) The following strategies for the prevention and treatment of the health effects of work stress were reviewed: i) surveillance of work stress, ii) improvement of psychosocial work environment, iii) education and information dissemination, and iv) reinforcement of occupational mental health services. Finally, the need for further investigation on the health effects of work stress and on the possible programs for the prevention and treatment in occupational health care system was discussed. PMID- 8510350 TI - ED noise: a legitimate patient care and staff stress issue. PMID- 8510351 TI - Spirituality: an important aspect of emergency nursing. PMID- 8510352 TI - Management of chronic care plan. PMID- 8510353 TI - New technique for starting i.v. lines (Wahid's maneuver) PMID- 8510354 TI - Memories of Operation Desert Shield/Storm. PMID- 8510355 TI - Early inpatient defibrillation by nurses applauded. PMID- 8510356 TI - A 24-year-old woman with "migraine headache". PMID- 8510357 TI - Management considerations in copperhead envenomation. PMID- 8510358 TI - Seabather's eruption, or "seal lice": new findings and clinical implications. PMID- 8510360 TI - Development of a prehospital nursing curriculum in Maryland. PMID- 8510359 TI - Noninvasive temporary cardiac pacing in the emergency department: a review and update. AB - NTP's superior safety and ease of use compared with other emergent pacing alternatives make it the emergency pacemaker choice for the acute stabilization of patients requiring pacing. The key to its success is timely use. The more quickly it is initiated, the more effective it will be. NTP represents a quick, effective treatment for asystole and symptomatic bradycardia. As emergency nurses, physicians, and paramedics become more experienced with its use, there is increased potential for enhanced survival rates for these patients. PMID- 8510361 TI - Disaster response: a review of the April 26, 1991, Kansas tornado. PMID- 8510363 TI - E coding: a missing link for injury prevention. AB - E codes are a practical, detailed, and feasible method of collecting much needed information about trauma morbidity. Emergency care providers are the key to ensuring accurate information because of their ability to obtain specific information from prehospital personnel or family. Charting the information on the emergency record will simplify the task for medical records coders, researchers, epidemiologists, and public health officials. The detailed information used for E codes is not just research trivia, but rather beneficial information for all emergency providers. A specific plan of care can be developed to address the medical and social needs of each patient. This in turn may help to reduce future injuries, whether they are caused by high-risk behaviors or repetitive abuse situations. PMID- 8510362 TI - Misuse of the emergency department by the elderly population: myth or reality? AB - OBJECTIVE: To determine the use pattern of the emergency department by people 65 years of age and older. DESIGN: Cross-sectional survey from chart audits and personal interviews of all people older than 64 years attending an emergency department in a Canadian teaching hospital. PARTICIPANTS: All patients older than 64 years attending the emergency department during the months of February, May, August, and November. Comparison samples of adults aged 16 to 64 years attending the same emergency department and patients older than 64 years attending the emergency department of a similar hospital during the same period were obtained. RESULTS: Fifteen percent of the total population attending the emergency department in 1 year were 65 years of age and older (N = 1744). The average age was 75 years; 57% were female, 53% were married, and 40% were widowed. Eighty four percent lived in their own homes and 6% lived in nursing homes. Twenty-two percent were classified as emergent, 75% as urgent, and 3% as deferrable; 45% were admitted. The discharge diagnoses were widely divergent, with the most common being soft-tissue injury (9.1%), fracture (7.1%), arteriosclerotic heart disease (6.1%), congestive heart failure (4.1%), and abdominal pain (3.4%). Patients tended to appear in the emergency department more frequently during the day shift (60%) and less frequently on weekends. Forty-five percent had never attended the emergency department or been admitted to hospital in the previous year; 30% had attended or been admitted once. CONCLUSION: Elderly persons do not misuse the services of the emergency department. They come because they are acutely ill; they are not frequent attenders, and their presenting complaints do require intervention (frequently hospitalization). The study findings are generalizable to the older population in the Hamilton-Wentworth region and raise such questions as whether some hospital admissions could have been avoided by earlier interventions in the community. PMID- 8510365 TI - Emergency department excuse form. PMID- 8510364 TI - Pharmacologic treatment of acute migraine and related headaches in the emergency department. AB - The care that an emergency nurse delivers is critical to the success of treatment of acute headaches. The emergency nurse should obtain a medication history from the patient and offer reassuring information about the relief afforded by prescribed medications and the adverse effects that can occur. Because the best treatment for a patient with recurrent headache syndrome is prevention, the emergency nurse should make sure that appropriate follow-up (e.g., headache specialist or counselor) is arranged before discharge from the emergency department. PMID- 8510366 TI - Emergency skills checklist. PMID- 8510367 TI - Emergency center documentation forms. PMID- 8510368 TI - Trauma assessment of the injured child. PMID- 8510369 TI - HIV and AIDS: a review of the recent MMWR literature. PMID- 8510370 TI - The personalized disaster plan narrative: an effective teaching tool for hospitals. PMID- 8510371 TI - One hospital's effort to improve pediatric emergency care: PALS for everyone. PMID- 8510372 TI - Trauma economics: suggestions for decreasing the cost of trauma care. PMID- 8510373 TI - Foote hospital emergency department: shattering a paradigm. PMID- 8510374 TI - Lessons learned. PMID- 8510375 TI - International update: two successful Canadian programs teach teenagers trauma prevention. PMID- 8510376 TI - Coping, caring, and heroism in the wake of Hurricane Andrew. PMID- 8510377 TI - A look at our new emergency department Clinton Hospital, Clinton, Massachusetts. PMID- 8510378 TI - Colony stimulating factor-1 in the induction of lupus nephritis. AB - In this study we examine the role of colony stimulating factor-1 (CSF-1) in the induction of lupus nephritis. The purpose of the study was to establish the relationship of CSF-1 to the prominent influx of macrophages (M phi) in the glomeruli of MRL-lpr mice with autoimmune lupus nephritis. The kidneys of MRL-lpr mice were examined before (< 12 weeks of age) and after (> 12 weeks of age) renal injury for CSF-1 transcripts by in situ hybridization. CSF-1 mRNA was detected at four weeks of age within glomeruli and increased with disease severity. To examine whether glomerular M phi (glom M phi) required CSF-1 we isolated M phi from the kidneys of MRL-lpr mice. Two types of glom M phi (with morphological and growth characteristics which correlated with the presence or absence of proteinuria) were isolated. Under CSF-1-free culture conditions, where the viability of glom M phi from proteinuric mice was maintained, glom M phi from pre proteinuric mice were unable to survive. Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom M phi (5 to 6 x), while viability of proteinuric glom M phi was diminished < 1.5 x. Additionally, CSF-1 supplementation induced a 10 x proliferation of pre-proteinuric glom M phi when compared to CSF-1-free medium. In contrast, proteinuric glom M phi did not proliferate in response to CSF-1. These studies suggest that CSF-1 induces macrophage proliferation and differentiation within glomeruli and, in turn, renal injury. PMID- 8510379 TI - Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. AB - Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c.). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET 1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10( 7) M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell. PMID- 8510380 TI - Catecholamines and phosphate excretion by the remnant kidney. AB - The remnant kidney (RK) exhibits an enhanced fractional excretion of phosphate (FEPi) even in the absence of parathyroid hormone (PTH). Thus, factors other than PTH contribute to this adaptive phosphaturia. Dopamine (DA) infusion is phosphaturic, whereas stimulation of adrenoreceptors is antiphosphaturic. Therefore, the hypothesis that alterations in catecholamines by the RK may be associated with the phosphaturia exhibited by this model was tested. Male Sprague Dawley rats were subjected to right nephrectomy and surgical ablation of the left renal poles. Four weeks later rats with a RK (N = 10) and control rats with intact kidneys (N = 9) were anesthetized and thyroparathyroidectomized (TPTX). Two hours after TPTX, urine samples were collected for measurements of urinary free DA excretion. Subsequently, 3% inulin in saline was infused for one hour and a 30 minute clearance was taken. The kidneys were then removed and frozen for determination of tissue norepinephrine (NE) and DA concentrations. Glomerular filtration rate was significantly lower in rats with a RK than in controls (0.57 +/- 0.07 vs. 0.83 +/- 0.08 ml/min/g kidney wt), whereas fractional excretion of phosphate (FEPi) was significantly higher (29.4 +/- 4.7 vs. 8.3 +/- 3.4%). Tissue NE concentration was significantly lower in the RK than in the control intact kidney (85.10 +/- 4.95 vs. 129.60 +/- 7.20 ng/g), whereas urinary DA excretion per nephron was significantly higher in the RK (0.12 +/- 0.02 vs. 0.04 +/- 0.006 pg/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510381 TI - Spatial organization of the extracellular matrix modulates the expression of PDGF receptor subunits in mesangial cells. AB - The aim of this study was to test the hypothesis that changes in the extracellular matrix environment regulate rat mesangial cell growth by modulation of the expression of both PDGF-receptor alpha- and beta-subunits. We investigated the mitogenic effects of the PDGF isoforms AA, AB and BB in conventional two dimensional (2D) culture on laminin, fibronectin, type I, IV and V collagen and in the different spatial organization of matrix in type I collagen gels in three dimensional culture (3D). In 2D culture PDGF BB was a potent mitogen, AB elicited an intermediate response while AA had no effect on cell proliferation. Extracellular matrix did not modify the PDGF responsiveness in 2D-culture. The different effects of the three PDGF isoforms were due to differential expression and isoform specific association of the PDGF-receptor subunits. Specifically, the beta-receptor was strongly expressed, whereas the alpha-receptor was only barely detectable on the cell surface. Metabolic labeling revealed synthesis and intracellular accumulation of the complete alpha-receptor protein, and treatment with suramin increased its surface expression, suggesting continuous receptor down-regulation by endogenous PDGF. Morphological and ultrastructural analysis in 3D culture revealed a change in mesangial cell phenotype, forming a branching network of multicellular structures. Assessment of proliferation in 3D culture showed quiescent cells and PDGF unresponsiveness. Investigation of the PDGF beta receptors revealed a rapid down-regulation in 3D culture; both receptor subunits were not detectable on the cell surface. We conclude that 3D culture promotes the induction of a different mesangial cell phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510382 TI - Number and dimensions of rat glomerular capillaries in normal development and after nephrectomy. AB - Glomerular capillary growth was studied in kidneys in five- to 540-day-old perfusion-fixed normal or sham-operated rats (C) as well as in unilaterally nephrectomized three-day-old (NN) and 120-day-old (NA) rats. The number and volume of mature glomeruli were estimated using the fractionator. The glomerular number was unaffected by neonatal or adult nephrectomy, but the number of mature glomeruli in all rats aged five days (19.1 +/- 2.0 x 10(3); +/- SD) was significantly smaller than for all the older animals (26.5 +/- 3.1 x 10(3)). The mean glomerular volume increased 59% and 20% for the NN and NA rats, respectively, versus the C rats. A capillary unit has been defined according to the number of loops in the glomerular capillary network by the use of topology. Glomerular capillary number, estimated using a physical disector, increased 53% for NN rats and 26% for NA rats. The glomerular capillary length was estimated on isotropic, uniform random sections, and increased 47% for NN rats and 12% for NA rats. The glomerular capillary surface area increased 54% for NN rats and 14% for NA rats. The diameter of the glomerular capillaries increased 8% for the mature NN versus the C rats. The rather unexpected findings are discussed and related to interesting relationships, including the law of Poiseuille and LaPlace. In conclusion, the growth of glomerular capillaries after neonatal and adult nephrectomy is performed by branching that is making new glomerular capillaries, instead of simply lengthening the existing capillaries. PMID- 8510383 TI - Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients. AB - To characterize morphologic changes in the early post-transplant period in cyclosporine-treated renal allograft recipients, we examined biopsies from three groups of cyclosporine-treated patients: normal function (N = 9), ischemic acute renal failure or "acute tubular necrosis" (N = 12), and cyclosporine toxicity (N = 7). Groups were compared with each other and with previously studied groups of azathioprine-treated patients and native kidney patients. The interstitial infiltrate commonly observed in normally functioning azathioprine-treated grafts was not observed in normally functioning cyclosporine-treated grafts, but two of nine such grafts had a significant venulitis, a change also seen in three of the patients with cyclosporine nephrotoxicity. "Acute tubular necrosis" (ATN) in cyclosporine-treated graft recipients was characterized by focal necrosis of complete tubular cross sections, a finding normally rare in other types of ATN, and by shedding into the tubular lumen of tubular cells with non-pyknotic nuclei, a finding supporting our previous observation of detachment of viable tubular cells in ATN but not in the normal kidney. Hyaline arteriolar thickening was the only morphologic finding on biopsy which distinguished patients with cyclosporine nephrotoxicity from other groups. In summary, the morphologic changes observed in cyclosporine-treated renal allograft recipients with ATN or normal function are quite different from those observed in azathioprine-treated patients. Cyclosporine appears to enhance the tubular injury observed in ATN. Hyaline arteriolar thickening is the main distinguishing feature of cyclosporine nephrotoxicity. PMID- 8510384 TI - Protein intake affects levels of G-protein subunits G alpha i2, G alpha i3, and G beta in rat glomerular membranes. AB - Using toxin-catalyzed ADP-ribosylation and specific immunoblots we examined whether the mass of G-protein subunits, G alpha s, G alpha i (includes G alpha i2, G alpha i3, and G alpha 0) and G alpha beta, in glomerular membranes was altered by dietary protein intake. ADP-ribosylation catalyzed by cholera toxin (CT) or pertussis toxin (PT) detected significant amounts of G alpha s or G alpha i in glomerular membranes from rats fed a low (6% casein) or a high (40% casein) protein diet. There was no significant difference in G alpha s content between glomerular membranes from low or high protein-fed rats. However, the amounts of G alpha i were significantly lower in glomerular membranes from rats fed a high protein diet when compared to glomerular membranes from rats fed a low protein diet. Two isoforms of immunoreactive G alpha s, 45 and 52 kDa proteins, were detected in glomerular membranes. The predominant isoform of G alpha s was a 52 kDa protein. As with ADP-ribosylation, immunoblots showed no significant difference in G alpha s content between glomerular membranes obtained from the two diet groups of rats. Also, immunoreactive G alpha i2, G alpha i3 and G beta were present in glomerular membranes. The mass of G alpha i2 and G alpha i3 was significantly lower in glomerular membranes of rats fed a high protein diet than in those of rats fed a low-protein diet. The decreased mass of total G alpha i, that is G alpha i2 and G alpha i3, was comparable to that seen with PT-catalyzed ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510385 TI - Juvenile cystic kidneys (jck): a new mouse mutation which causes polycystic kidneys. AB - We have characterized a new recessive mutation in the mouse which predisposes to the development of polycystic kidney disease. This mutation, called juvenile cystic kidneys (jck), arose in a transgenic line of mice, but appears unrelated to the transgene since it segregates freely from it. While focal cysts are evident in affected animals as early as three days of life and the disease is progressive, the mice are fertile and generally survive to four or more months of age. Complementation analysis indicates that the jck mutation is not allelic with three other known recessive polycystic kidney mutations (cpk and two as yet unnamed mutations), and linkage studies demonstrate it is unlikely to be allelic with a fourth (pcy). The study of these five mutations and their interactions should prove useful for understanding the mechanisms required to maintain the normal integrity of renal tubules. PMID- 8510386 TI - Metabolic effects of hemodialysis with and without glucose in the dialysate. AB - This study was conducted in eight acute renal failure patients undergoing mechanical ventilation to test if the addition of glucose in the dialysate prevents metabolic and hormonal changes induced by hemodialysis. Hemodialysis was performed with a bicarbonate dialysate, a polyacrilonitrile membrane and a continuous heparinization. Two four-hour hemodialysis sessions were performed in each patient: one without glucose (GFD) and one with glucose (GD) in the dialysate at a concentration close to each patient's initial plasma glucose concentration. Oxygen consumption and carbon dioxide elimination, glucose insulin, aceto-acetate and free fatty acids were measured before, during and after the sessions. Oxygen consumption and carbon dioxide elimination were measured with a system using a mass spectrometer. Hemodynamic state and temperature remained constant. Before hemodialysis, respiratory quotient (RQ) values were the same in both groups. There was no change in RQ during GD. There was a decrease in RQ during GFD. Glucose and insulin concentrations decreased during GFD and remained unchanged during GD. Aceto-acetate concentration remained constant under both conditions. Free fatty acids concentration increased to the same extent during GD and GFD. The authors conclude that the addition of glucose in the dialysate prevents the decrease in RQ induced by hemodialysis. This effect is most likely related to a decreased mobilization of non-glucidic fuels. PMID- 8510387 TI - Hemodialysis vascular access morbidity in the United States. AB - Extensive morbidity related to hemodialysis vascular access exists among end stage renal disease (ESRD) patients, but the risk factors for this morbidity have not been extensively studied. Medicare ESRD patient data were obtained from 1984, 1985, and 1986. Hospitalization for vascular access morbidity (ICD-996.1, 996.6, or 996.7) was analyzed among prevalent patients and, using survival analysis, among incident patients to assess sex, age, race, and underlying cause of renal failure as risk factors. We found that 15 to 16% of hospital stays among prevalent ESRD patients were associated with vascular access-related morbidity. Black race, older age, female sex, and diabetes mellitus as a cause of kidney failure were all independent risk factors for access-related morbidity. The rate ratio comparing Blacks to Whites was 1.12 (95% C.I., 1.09, 1.16); > 64 years to 20 to 44 years, 1.53 (1.46, 1.59); men to women, 0.81 (0.79, 0.84); and diabetes to glomerulonephritis, 1.29 (1.24, 1.35). We conclude that hemodialysis vascular access malfunction causes much hospitalization among ESRD patients. Women, Blacks, the elderly, and diabetics appear to be at particularly high risk, and additional studies are needed to understand these patterns. PMID- 8510388 TI - Potassium supplementation ameliorates mineralocorticoid-induced sodium retention. AB - Potassium depletion induced by dietary potassium restriction causes sodium retention while potassium supplementation augments urinary sodium excretion. The role of external potassium balance in modulating mineralocorticoid-induced sodium retention in humans is unknown. Accordingly, eight healthy subjects were studied at the Clinical Research Center receiving a constant diet providing (per kg body wt) sodium 2.5 mmol, potassium 1.1 mmol daily. After establishing basal sodium and potassium balance over three days, each subject received 9 alpha fludrocortisone 0.4 mg/day for 10 days. Subjects were studied twice, four to eight weeks apart, in a double blind, randomized crossover design receiving either placebo or additional KCl (80 mmol/day) over the 10 day study period. Serum potassium concentrations were unchanged from basal values on KCl while the values fell (4.1 +/- 0.1 vs. 3.4 +/- 0.1 mmol/liter, P = 0.01) on placebo. Urinary sodium excretion decreased with fludrocortisone administration in both groups, but this decrease reached significance only in the placebo group. Furthermore, during fludrocortisone administration the sodium excretion rates on KCl were significantly higher compared to the values noted on placebo (134 +/- 8 vs. 112 +/- 13 mmol/day, P = 0.01). Body weight recorded after 10 days of fludrocortisone administration was higher on placebo compared to KCl (72.3 +/- 2.8 vs. 71.6 +/- 2.8 kg, P = 0.01). Plasma renin activity, and aldosterone concentrations decreased on fludrocortisone while atrial natriuretic peptide levels increased. These studies suggest that amelioration of hypokalemia attenuates mineralocorticoid-induced sodium retention. Therefore, potassium depletion may contribute to the mineralocorticoid-induced sodium retention. PMID- 8510389 TI - Parathyroid sensing of the direction of change of calcium in uremia. AB - It could be advantageous for the parathyroids to be able to sense not only the absolute concentration of extracellular Ca2+, but also the rate and direction of change of Ca2+, thereby allowing the parathyroids to respond earlier to threats to Ca2+ homeostasis. By using high and low Ca2+ dialysis in a single session, we examined the parathyroid response to direction of change of Ca2+ during acute Ca2+ perturbation in nine hemodialysis patients. Separate PTH/ionized calcium (PTH/iCa) response curves were generated for rising Ca2+ and falling Ca2+. Significant directional hysteresis (higher PTH level during falling than during rising Ca2+) was found. During hypercalcemia, PTH levels were between 2.2 and 1.6 times higher at iCa concentrations of between 0 and +0.1 mM above the baseline iCa, when Ca2+ was falling than when it was rising. During the phase of induced hypocalcemia, parathyroid fatigue was seen in six of the nine patients. Fatigue patients tended to have higher basal PTH (1-84) levels than those not showing fatigue. The existence of fatigue provides an explanation for directional hysteresis during hypocalcemia, and therefore parathyroid sensing of the direction of change of Ca2+ could not be assessed during hypocalcemia. These studies demonstrate a capacity of the parathyroids to sense the direction of movement of Ca2+ during hypercalcemia. PMID- 8510390 TI - Forty-five year follow-up after uninephrectomy. AB - This study examined the consequences of nephrectomy in United States Army personnel who lost a kidney due to trauma during World War II (WWII). Records of 62 servicemen who underwent nephrectomy at an average age of 25 years were obtained. Mortality was compared with that of WWII servicemen of the same age. Medical records of 28 deceased subjects were reviewed for evidence of kidney disease. Medical histories were obtained and blood pressure and kidney function were assessed in 28 living subjects. Two subjects could not be located, and four subjects declined to participate. Mortality at 45 years was not increased in nephrectomized subjects. Kidney disease present in six of 28 deceased subjects was attributable to causes other than prior nephrectomy. Glomerular sclerosis was not increased in 10 subjects who had autopsy examinations. The prevalence of hypertension was not increased in living subjects. Five of 28 living subjects had abnormal renal function manifested by proteinuria greater than 250 mg/day in four cases (range: 377 to 535 mg/day) and serum creatinine levels greater than 1.5 mg/dl in three cases (range: 1.7 to 1.9 mg/dl). Conditions other than nephrectomy could have contributed to impairment of renal function in each of these subjects. These findings suggest that uninephrectomy in young adults has few major adverse consequences over 45 years. PMID- 8510391 TI - A splicing mutation in the alpha 5(IV) collagen gene of a family with Alport's syndrome. AB - DNA sequence analysis of the alpha 5(IV) collagen chain gene (COL4A5) was carried out between exon 47 and 51, which encode the noncollagenous (NC) domain, in eight Japanese families with Alport's syndrome. In one family with X-linked inheritance of the disease, a point mutation (G to C) was found at the 3' end of exon 49 in the COL4A5. This mutation converted the codon of a conserved methionine-1601 to the codon for isoleucine, and also altered the normal splicing process. The polymerase chain reaction (PCR) product amplified between exons 47 and 51 of cDNA in the affected male (hemizygote) of this family contained four fragments with various molecular weights, whereas that of a normal control contained one with the expected molecular weight. Sequence analysis of the PCR fragments of the male patient revealed various types of alternative splicing between the exons, reflecting the various sizes of PCR fragments. The PCR amplified product of the cDNA of the affected female (heterozygote), on the other hand, contained a fragment with the same molecular weight as the normal control. Sequence analysis of the PCR fragments of her cDNA revealed normal splicing and no point mutation at the 3' end of exon 49. These findings indicate that this point mutation at the consensus sequence not only converted the codon but also altered the splicing between these exons encoding the NC domain of the COL4A5. Resulting in missense of the alpha 5(IV) chain, changing a large portion of the carboxyl terminal crosslinking NC domain, this mutation can alter the normal structure of the type IV collagen network.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510392 TI - Early dosing practices and effectiveness of recombinant human erythropoietin. AB - In a national longitudinal-cohort study of 59,462 end-stage renal disease (ESRD) patients, we examined dosing and effectiveness of erythropoietin (EPO) during the first year of its use in clinical practice (July 1989 through June 1990). In unadjusted and multivariate analyses of Medicare claims data, the mean dose of EPO prescribed was: relatively small and similar for initial and maintenance therapy, 2752 (95% confidence interval 2740 to 2764) and 2668 (95% confidence interval 2654 to 2682) units, respectively; lower when initial therapy was started later (591 units lower in September 1989 and 760 units lower in November 1989 vs. July 1989, P < 0.0001); lower by 135 units during initial therapy and by 116 units during maintenance therapy for females (who weigh less) compared to males (P < 0.001); and lower by 400 units for patients treated in for-profit versus not-for-profit centers. In multivariate analysis: hematocrit response was less and mean maintenance dose was 298 units and 621 units greater for patients whose ESRD was due to multiple myeloma and sickle cell disease, respectively, compared to those with hypertension-related ESRD (P < 0.01); and hematocrit response was logarithmically related to dose [hematocrit = 0.97 ln (dose), P < 0.0001]. Forty-four percent of patients had a hematocrit > or = 30 after four months of therapy. The percent of patients transfused during three month periods before and after therapy decreased from 20% to 5%, respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510393 TI - Sleep disordered breathing in ESRD: acute beneficial effects of treatment with nasal continuous positive airway pressure. AB - Complaints about sleep and daytime alertness are common in ESRD patients. Eight consecutive ESRD patients with a sleep complaint were studied with all-night polysomnography. All were found to have significant sleep apnea with a mean apnea/hypopnea index (AHI) of 64 +/- 41.6 episodes per hour of sleep (range 7.5 to 140/hr of sleep). The majority of apneas were of the central or mixed variety causing severe fragmentation of sleep and frequent awakenings. Treatment was attempted with nasal continuous positive airway pressure (NCPAP). NCPAP was highly successful in six of the eight patients, reducing the mean AHI to normal or near normal levels (6.0 +/- 3.8/hr of sleep, P < 0.02 vs. baseline). The quality of sleep was significantly improved with statistically significant decreases in light stage 1 sleep, and nocturnal oxygenation improved with statistically significant increases in low SaO2 values. Five of six responders reported that they awoke feeling more alert and fewer times from sleep. The etiology of sleep apnea in ESRD is unknown although the frequent central apneas suggest a dysfunction of central respiratory control resulting from the effects of renal failure. Sleep-related complaints in patients with ESRD are likely to result from sleep apnea, a sleep disorder that can be diagnosed with polysomnography and treated with NCPAP. PMID- 8510394 TI - Complement activation during OKT3 treatment: a possible explanation for respiratory side effects. AB - Respiratory side effects that sometimes occur during treatment with anti-CD3 MAb OKT3 might result from pulmonary sequestration of activated neutrophils. Therefore, we studied complement activation in relation to activation and pulmonary sequestration of neutrophils during antirejection treatment with OKT3. In each of nine patients studied, plasma C3a-desarg and C4b/c levels increased compared with pretreatment values already in the first sample taken 15 minutes after the first dose of OKT3 (P < 0.05), with peak values at 15 and 30 minutes, respectively. Levels of neutrophil degranulation product elastase (complexed to alpha 1-antitrypsin) also increased already at 15 minutes after the first dose of OKT3 (P < 0.05), which is before elevated levels of the cytokines TNF alpha, IL-6 or IL-8 were detectable. In contrast, upon subsequent OKT3 administrations or in the control group treated with methylprednisolone, neither complement activation, cytokine release nor neutrophil degranulation occurred. In five studied patients treated with OKT3, pulmonary sequestration of radiolabeled granulocytes was observed from 3 until 15 minutes after the first dose of OKT3, together with peripheral blood granulocytopenia, which lasted at least 30 minutes. In conclusion, we demonstrate a simultaneous activation of complement and pulmonary sequestration of activated granulocytes immediately following the first dose of OKT3. These phenomena may be involved in the development of respiratory side effects complicating this therapy. PMID- 8510395 TI - Role of monocytes in cryoglobulinemia-associated nephritis. AB - Several monocyte-macrophage functions were found to be defective in cryoglobulinemic patients. Nevertheless, monocytes actively phagocytizing cryoglobulins have been frequently found in kidney specimens from these patients. Whether subsequent degradation of the ingested immune material is effective, however, is still unknown. Monocytes from eight cryoglobulinemic patients (4 with active disease and associated nephritis and 4 inactive cases without nephritis) and eight normal controls of same sex and similar age were analyzed. Monocytes from patients with active cryoglobulinemia and associated nephritis were found to be able to ingest, but unable to catabolize, cryoglobulins, as shown by electron microscopy using gold-labeled goat IgG to human IgG and IgM in 18-hour cultured suspensions. Synthesis and maturation of monocyte cathepsin D, one of the most important lysosomal proteases, were analyzed in the same subjects. Purified monocytes were cultured in presence or absence of cryoglobulins for 18 hours at 37 degrees C in RPMI medium and labeled with 35S-methionine. The various forms of cathepsin D were separated by electrophoresis and visualized by fluorography. Results from cultures of monocytes from clinically active cryoglobulinemic patients with nephritis suggest that intracellular transport of newly synthesized cathepsin D was impaired and the release into the medium of precursor polypeptides of the enzyme enhanced in each experimental condition. Since procathepsin D is susceptible to activation in pathologic conditions lowering local pH (such as in inflamed tissues), these data suggest that monocytes from patients with active cryoglobulinemia and associated nephritis have a propensity to exert phlogistic effects via secretion of procathepsin D in tissues. PMID- 8510396 TI - An in vitro method for the determination of protein turnover in incubated proximal tubule segments. PMID- 8510397 TI - Mechanisms of ischemic acute renal failure. PMID- 8510398 TI - Pathophysiology of low renin syndromes: sites of renal renin secretory impairment and prorenin overexpression. PMID- 8510399 TI - [Effect of the amino acid content of breast milk supplements on the amino acid profile in the plasma of newborn infants: human albumin in comparison with Eoprotin]. AB - The influence of amino acid composition of two human milk fortifiers (Eoprotin, Milupa AG, Germany, and human albumin) on plasma amino acid profiles was studied in 28 preterm infants after a 14-day feeding period. The concentrations of total essential amino acids increased in both feeding groups significantly if compared to the period without supplementation; only the concentrations of methionine and phenylalanine in the eoprotin group and those of threonine, methionine and isoleucine in the human albumin group did not increase significantly. However, only the concentrations of isoleucine (Eoprotin: 79 +/- 19 mumol/l; human albumin: 45 +/- 20 mumol/l, p < 0.001) and methionine (Eoprotin: 26 +/- 10 mumol/l, human albumin: 16 +/- 10 mumol/l, p = 0.014) were significantly different between the two feeding groups. There was a significant correlation between the differences in the serum concentrations and the ones of each essential amino acid concentration in the fortifiers (r = 0.951). The results indicate that the amino acid composition of human milk fortifiers must be taken into consideration to achieve optimal nutritional management of preterm infants. PMID- 8510400 TI - [Leipzig neonatal screening center--experiences with introduction of screening for congenital hypothyroidism]. AB - The development of neonatal screening for congenital hypothyroidism in the GDR and particularly in Saxony after German reunification is described in this paper. The results of the studies and the experiences in respect of realisation and organisation of the screening for hypothyroidism in the screening centre of Leipzig are discussed. Measurement of TSH in the blood spot of about 65,000 newborn yielded an incidence rate of congenital hypothyroidism of 1:3,200. The onset of therapy within the first three weeks of life has been ensured until now since no children with congenital hypothyroidism were involved in cases of occasionally delayed blood sampling and/or postal delay. However, there has been some organisational disparity due to individually different handling of health insurance fund payments of screening fees for hypothyroidism in Saxony and also in the other federal states. The disadvantages of this lack of uniform regulations are explained. Neonatal screening for evidence of congenital adrenal hyperplasia by determining 17-alpha-hydroxyprogesterone, is under preparation. PMID- 8510401 TI - [Clinico-neurologic and neurophysiologic findings in hemophilic boys and their effect on social integration]. AB - Prophylactic substitution of severe (sometimes even moderate) haemophilia (home self-treatment) has, besides other measures, not only had a positive effect on the findings in the joints but also on the danger of bleeding in the CNS. The injuries of the head in haemophiliacs are analysed and the social integration is shown (school, occupation, spare-time planning). Compared with previous information in literature the high incidence of pathological EEG findings has decreased. Without observing clinically perceptible deficits, the acoustically evoked brain stem potentials were often found to be altered. PMID- 8510402 TI - [Brachydactyly type A4 (brachymesophalangia II and V, Temtamy type). A rare type of brachydactyly]. AB - Brachydactyly is classified into 5 main types. In type A brachydactylies the shortening is mainly confined to the middle phalanges of the digits and toes. Brachydactyly type A4 is characterised by brachymesophalangy II and V. We found this rare type of brachydactyly in a child and his mother. We examined the hands and feet of these individuals radiologically. The reported malformation had affected members of 2 respectively 3 generations. There is no doubt about the autosomal dominant mode of inheritance. PMID- 8510403 TI - [Lymphoproliferative syndrome after HiB and polio preventive vaccination?]. PMID- 8510404 TI - [Osteomyelitis/osteitis after BCG vaccination?]. PMID- 8510405 TI - [Physician responsibility of confidentiality]. AB - Summarizingly it is to be mentioned that, concerning the professional secrecy, the principle is held that the physician is allowed to speak as much as it is necessary and he must be silent as far as it is possible. The physician is entitled to reveal but not obliged to do so as far as he has been exonerated from the professional secrecy or as far as the revelation is necessary for the protection of a higher legal proceeding. This is taken into consideration also for evidence in judicial proceedings. Apart from legal informational obligations at first, however, not the physician but the patient defines the breadth of allowable infringements. Only when the professional secrecy collides with the legal matters of third persons the physician himself gets into compulsions of decision. Taking into consideration the criminal law the maintenance as well as the infringement of the professional secrecy remain without consequences for the physician, if the translegal critical state is present. In such cases, however, he should endeavour to keep the dangers which brings his silence for others as insignificant as possible. PMID- 8510406 TI - [Once again: "Hypohydrotic ectodermal dysplasia as a cause of recurrent hyperthermia in an young infant" by A. Dittmer et al]. PMID- 8510407 TI - [Comment on the contribution by Dr. F. Schnitger. Therapy of acute diarrhea]. PMID- 8510408 TI - [General lipid-screening in childhood is productive. Interview by Dr. med. Fritz Schnitger]. PMID- 8510409 TI - [Growth factor-induced stimulation of proteoglycan synthesis in corneal endothelium cells]. AB - BACKGROUND: Cultured bovine corneal endothelial cells (CEC) synthesize heparan sulfate and dermatan sulfate containing proteoglycans and distribute them between different compartments. METHODS AND RESULTS: [35S]sulfate labelled proteoglycans are found associated with the cell layer, secreted into the culture medium and deposited into the underlaying extracellular matrix. In the presence of basic fibroblast growth factor (bFGF)-a strong mitogen for CEC-subconfluent cells incorporate [35S]sulfate into the sulfated proteoglycans at a rate three times higher as compared with the proteoglycans of CEC in the absence of bFGF. The enhanced proteoglycan synthesis is accompanied with a shift in the proteoglycan distribution pattern. While in control cells the cell-associated heparan sulfate accounts for about 30% of the total glycosaminoglycans under the influence of bFGF the HS percentage increases to approximately 60%. CONCLUSIONS: CEC synthesize and deposit endogenous bFGF into the extracellular matrix. Heparitinase treatment of the extracellular matrix releases bFGF activity which is able to stimulate the 35S incorporation into proteoglycans in a comparable manner as exogenous bFGF but does not influence the proteoglycan distribution pattern. Pretreatment of the matrix-bound bFGF activity with polyclonal antibodies against bFGF abolishes its stimulating activity. PMID- 8510410 TI - [Cytokines in uveal melanoma. Original title: uveal melanoma cytokines]. AB - Cytokines may be important in both the pathophysiology an ocular morbidity associated with treated and untreated uveal melanomas. In this study we used message amplification phenotyping to identify cytokines present in uveal melanoma samples. A number of cytokines were noted that have been associated with tumor progression, neovascularization, and inflammation in other malignancies. Interferongamma was commonly found in spindle cell tumors. Only one of 16 tumors had detectable levels of TNF-alpha and this occurred in one of two patients who developed metastatic disease. PMID- 8510411 TI - [Physical principles of sclerostomy]. AB - Various sclerostomy procedures, performed ab interno and ab externo have found increasing interest for some time. With few exceptions, invasive procedures are described, in which laser energy is transmitted by means of specially designed fibers and probes ab interno and ab externo to the perforation site. Laser energy sources, ranging from the UV through the visible to the IR range have been described. Thus far, no detailed models quantifying the ablation mechanism of such sclerostomy procedures have been published. All such procedures have in common that the wavelength of the laser should be matched to water absorption bands. Now more sophisticated models describing the action mechanism of various lasers begin to emerge. A system described by us takes advantage of the high efficiency of rapid steam explosions occurring in a closed space, i.e. in the region delimited by the probe end and the fistula bottom. The high efficiency of such mechanisms has been verified in model experiments on porcine eyes in vitro. Electron microscopical results also show that the amount of thermal damage is negligible and that there is very little wavelength-dependence. This permits the adoption of "common" laser energy sources such as diode and Nd:YAG lasers. The clinical survival probability of fistulas as related to the amount of collateral damage is controversial. PMID- 8510412 TI - [New approaches in topical drug administration and treatment of the dry eye]. AB - The collagen shield is a contact lens-shaped collagen matrix that can be impregnated with a drug during hydration or manufacture and then, when placed on the cornea, acts as a reservoir, dissolving slowly and releasing the drug over time. This new ocular drug delivery system has proven useful in the treatment of corneal infections and the prevention of graft rejection. The lubricating effect of the dissolving shield matrix may palliate dry eye symptoms, but the shields are not useful as a treatment for keratoconjunctivitis sicca because they must be applied in the physician's office and they are not transparent. A new formulation of collagen and cetyl alcohol particles suspended in a methylcellulose vehicle (Lacrisomes) is being developed to relieve symptoms in dry eye patients. A similar system, with the addition of therapeutic agents during manufacture (Collasomes), is being tested for drug delivery to the ocular surface. The advantages of both of these systems would be their ease of application and minimal interference with vision. PMID- 8510413 TI - [Treatment of central serous choroidopathy with the beta receptor blocker metoprolol (preliminary results)]. AB - Numerous theories have been proposed to explain the origin of central serous choroidopathy (CSC). However, it has been shown recently that there is a close relationship between CSC and type A-behaviour pattern (TABP) which is characterized by high adrenergic activity in the body. It is interesting to note that one of our patients who had chronic central serous choroidopathy, and metoprolol treatment for hypertension during one year, developed a recurrence of CSC three weeks after cessation of metoprolol treatment. This was one of the reasons to start this treatment modality for CSC. In this study, we present 6 cases of CSC in which the diagnosis was established by ophthalmoscopy and fluorescein angiography. In these patients, we proposed to analyse the relationship between CSC and a high adrenergic activity by the use of a selective beta-blocker (metoprolol; 50 mg tablets, twice daily). In two of the six cases, laser photocoagulation was also performed prior to commencement of the metoprolol treatment. Visual acuity improved in two patients, stayed at 1.0 in three patients and stabilized on the pretreatment level (0.8) in one patient (case-5). However, the symptoms (metamorphopsia and micropsia) and the signs (serous retinal detachment and angiographic hyperfluorescence) decreased or disappeared in all patients after treatment. Also visual complaints in all patients improved subjectively. No recurrences were noted during the metoprolol treatment in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510414 TI - [Therapy of cystoid diffuse macular edema after uveitis and cataract surgery with the carbonic anhydrase inhibitor acetazolamide (Diamox)]. AB - BACKGROUND: Observations made by Cox, Bird et al. (1988), who first used acetazolamide (Diamox) for treatment of macular edema of various origin in a higher number of patients, let assume a positive effect of this therapy on fluid accumulation specifically inside the inner retinal layers. Based on these studies 15 patients (20 eyes) with cystoid or cystoid-diffuse macular edema were treated with acetazolamide in a pilot-study. MATERIALS AND METHODS: Eleven patients (fifteen eyes) had postuveitic macular edema, four other patients (five eyes) had cystoid edema following cataract surgery. Patients with additional diseases causing macular edema of retinal vascular origin were excluded. The initial dose was 500 mg daily. In one patient responding to therapy the dose was gradually reduced after three weeks down to a minimum of 125 mg every second day. For evaluation of the therapeutical results fluorescein angiography and visual acuity were taken into account. RESULTS: Eleven patients (fourteen out of twenty eyes) showed a distinct therapeutical effect with decrease of macular edema in repeatedly controlled fluorescein angiography. All these patients had a subjective improvement of vision which correlated with an increase of visual acuity in exactly one half of all patients. Therapy was stopped, when the macular edema had still appeared unchanged in angiography after three weeks or when--in spite of fluid reduction in angiography--no improvement of visual acuity could be obtained in the next two months. The maintenance dose showed large individual variation with a minimum of 125 mg every second day and a maximum of 250 mg per day. Attempts to stop therapy resulted in a early reappearance of the edema of original extension with corresponding deterioration of visual acuity and sensitivity of central visual field. In a few patients even the reduction of the dose below the individual maintenance dose could be demonstrated angiographically. All patients were under continuous internal medical control, permanent side-effects of acetazolamide with the doses used in this study were not seen. CONCLUSIONS: The results show that acetazolamide is a basically effective agent against cystoid macular edema and that a therapeutical trial is justified based on the treatment criteria of this study. The factors limiting the therapeutical effect of acetazolamide cannot yet be evaluated on the basis of the small amount of patients in this pilot-study. Considering the patient data a time factor depending on the period between onset of edema-related symptoms and begin of treatment is likely. In the group of unsuccessfully treated cases we had the patients with the longest period of preexisting edema (more than one year) of the study. PMID- 8510416 TI - [Spontaneous growth inhibition in retinoblastoma]. AB - Report on 8 cases with spontaneous arrest of retinoblastoma. The incidence was 3.2% which is approximately 1000 times more than in other malignant tumors. Multifocal lesions suggesting that this form of "regression" may not be a regression at all. Spontaneous arrest of retinoblastoma is obviously a lesion of low malignant potential. The presence of a spontaneous arrest of retinoblastoma necessitates genetic counselling and examinations of the eyes in the offspring. Synonymous names are: 1. Spontane Ruckbildung eines Retinoblastoms (spontaneous regression of retinoblastoma), 2. Retinoma, 3. Retinocytoma, 4. benign variant of retinoblastoma, 5. spontaneous arrest of retinoblastoma, 6. spontaneous cure of retinoblastoma. PMID- 8510415 TI - [Pneumatic retinopexy--a study of 7 years experience]. AB - BACKGROUND: The goal of this study is the evaluation of effectivity and the complications of pneumatic retinopexy in the treatment of rhegmatogenous retinal detachment as a long-term follow-up. MATERIAL AND METHODS: This retrospective long-term study covers 89 eyes with rhegmatogenous retinal detachment treated by pneumatic retinopexy between January 1985 and December 1991. With a postoperative follow-up averaging 4.8 years, it constitutes the longest such period published to-date in literature. RESULTS: The first intervention induced anatomical healing in 73% of all cases. However, 5.5% relapsed with retinal detachment after one month. Following a second intervention (excepting 2 cases) performed with conventional retinal detachment surgery consisting of exoplants + kryopexy + subretinal drainage, successrate was stepped up 97%. A total of 5 eyes required maximum surgery, i.e. vitrectomy + silicone oil tamponade. In 3% this procedure presented the third intervention. Finally anatomical healing was attained in 100% of the eyes. However, after one month 18% developed new retinal tears and after a follow-up period of 5.5 years this figure had risen to 27.7%. CONCLUSION: Judged on the basis of the above results, pneumatic retinopexy should only be recommended for the very simplest cases of rhegmatogenous retinal detachment (a single tear in the upper fundus half between 10 and 2 o'clock and no pathological changes in the lower fundus half). Also, check-ups at short intervals are required following pneumatic retinopexy. In our opinion standard buckling surgery with additional gas tamponade is preferable. PMID- 8510417 TI - [Choroidal effusion and expulsive hemorrhage in penetrating interventions--lesson from 26 patients]. AB - BACKGROUND: The aim of this study was, to analyze in cases of choroidal effusion and expulsive hemorrhage the surgical procedures and to derive recommendations to handle the expulsive event properly and adapted to the phase of the surgical procedure. MATERIAL: We report on 25 patients (27 eyes), 17 women and 8 male, who suffered from choroidal effusion and/or expulsive hemorrhage during or following surgery, in which the eye was opened. The age at the time of the event was between 52 and 90 years (median 80). 21 times the complication arrived during cataract surgery (age 57-90 years (median 81), five times during or following fistulating glaucoma surgery (age 55-84 years (median 63) and once during corneal transplant surgery (age 52 years). RESULTS: Old age (50% of the patients > or = 81 years old), local anesthesia (except in one case), then arterial hypertension, coronary heart disease, myocardial infarction are accompanying characteristics in patients with this event. Choroidal effusion and expulsive hemorrhage can usually be managed, if wound closure is always possible and the necessary counterpressure can be applied. This is the case with a step incision and with at least three preplaced strong silk "safety" sutures (7.0 silk). With this technique all our own patients could be managed, but the characteristic of the six patients who were referred to us was, that no safety sutures had been placed. Three cases developed choroidal effusion following filtering procedures in glaucomatous eyes. After revision at the 10th to 15th day following expulsive hemorrhage with evacuation of the suprachoroidal hemorrhage, restoration of the anterior segment and of the vitreous cavity, in three of five desperate patients useful function from hand movement to 0.6 could be reached. Echography is used to determine the time the coagula are liquified and the moment to evacuate the hemorrhage. This is between 10 to 15 days. CONCLUSIONS: Basically any expulsive event has to be managed by creating counterpressure. This means working in a closed system as long as possible. As long as not a tunnel incision is made, respectively when an expression technique with a large incision is used, together with a step incision at least three strong silk 7.0 "safety" sutures have to be preplaced, to allow a secure closure of the wound in any moment during surgery. If an expulsive event is the cause of protrusion of vitreous, vitrectomy is wrong because this lowers intraocular pressure. Urgent is the closure of the wound, even if vitreous and iris become squeezed into the wound. A sclerotomy is indicated only, if the wound can't be closed. Even if the expulsive hemorrhage leads first to amaurosis, evacuation of the hemorrhage together with revision of the anterior segment, vitrectomy and refilling may bring back some useful visual function. The surgical technique for revision, but also for measures in the different phases of cataract surgery are described in detail. PMID- 8510418 TI - [Photorefractive keratectomy for correction of myopic astigmatism]. AB - Nine eyes underwent superficial ablation with excimer laser for treatment of compound myopic astigmatism. In eight of the eyes, corneal cylinder was naturally occurring, and in one eye the astigmatism had developed following retinal detachment surgery. All patients have been followed for 9 months. The pre- and postoperative cylinder was -2.7 +/- 0.4 diopters and -1.3 +/- 0.4 diopters, respectively, while the pre- and postoperative spherical equivalent was -4.7 +/- 0.4 diopters and -1.3 +/- 0.4 diopters, respectively. Uncorrected acuity improved from a preoperative mean of 20/300 to a postoperative mean of 20/40. Patients with a residual refractive error often demonstrated reasonably good unaided acuity. Toric ablations with the excimer laser can be performed at the same time as ablations for myopia, and appear to represent a promising strategy for correction of compound myopic astigmatism; the relative safety and efficacy of this procedure, and of combined radial and astigmatic keratotomy remain to be determined. PMID- 8510419 TI - [Stability of refraction 18 months after photorefractive keratectomy with excimer laser]. AB - One-hundred-fourty-eight normal, sighted eyes, treated for myopia with argon fluoride 193-mm excimer laser, were analyzed 18 months postoperatively with respect to stability of refraction. Mean refraction 18 months after surgery was 0.32 D (+/- SD 0.89), a figure which was not significantly different from mean refractions at 12 and 15 months postoperatively. Also at 18 months, 86% of the eyes had an uncorrected visual acuity > or = 20/40, and 82% of the eyes were within 1.00 D of intended refraction (i.e. emmetropia). These percentages, which are directly related to postoperative refraction, are similar to those noted at 12 months after surgery. Although it may be too early to conclude that the 18 month refractions represent a definitive predictor of future refraction, the numerous similarities between the 12- and 18-months data presented in this study tend to suggest stability of refraction 18 months after excimer laser photorefractive keratectomy for myopia. PMID- 8510420 TI - [Total intravenous anesthesia. Premedication, total intravenous anesthesia and postoperative sedation]. PMID- 8510421 TI - [Advantages and disadvantages of anesthesia induction with etomidate in comparison with barbiturates]. PMID- 8510422 TI - [Is the use of short-acting anesthetics for long-term sedation meaningful? The pharmacological aspect]. PMID- 8510423 TI - [With what substances is total intravenous anesthesia primarily feasible and significant? The clinical aspect]. PMID- 8510424 TI - [Administration possibilities in total intravenous anesthesia]. PMID- 8510425 TI - [The role of total intravenous anesthesia in obstetrics]. PMID- 8510426 TI - [The role of total intravenous anesthesia in pediatric surgery]. PMID- 8510427 TI - [The role of total intravenous anesthesia in heart surgery]. PMID- 8510428 TI - [The role of total intravenous anesthesia in outpatient anesthesia]. PMID- 8510429 TI - [The role of total intravenous anesthesia in liver and kidney insufficiency]. PMID- 8510430 TI - [Supplementing regional anesthesia with intravenous anesthesia]. PMID- 8510431 TI - [Total intravenous anesthesia vs.inhalation anesthesia]. PMID- 8510432 TI - [Advantages and disadvantages of anesthesia induction with midazolam and S ketamine in comparison with barbiturates]. PMID- 8510433 TI - [Does total intravenous anesthesia have an effect on the course of the postoperative phase?]. PMID- 8510434 TI - [The choice of substances for short-lasting postoperative sedation and analgesia]. PMID- 8510435 TI - [The choice of substances for long-term sedation and analgesia]. PMID- 8510436 TI - [The monitoring of analgesia and sedation in the postoperative phase and in intensive medicine]. PMID- 8510437 TI - [The choice of intravenous anesthetics and relaxants for emergency medicine]. PMID- 8510438 TI - [Pharmacodynamics and pharmacokinetics of the newer intravenous anesthetics (etomidate, propofol, S-ketamine)]. PMID- 8510439 TI - [Advantages and disadvantages of anesthesia induction with propofol in comparison with barbiturates]. PMID- 8510440 TI - [Advantages and disadvantages of the use of alfentanil/sufentanil for anesthesia induction in comparison with fentanyl]. PMID- 8510441 TI - [Advantages and disadvantages of the use of the newer muscle relaxants for anesthesia induction]. PMID- 8510442 TI - [The effect of premedication on the methods of total intravenous anesthesia]. PMID- 8510443 TI - [Nursing schools in the canton Zurich: ever more students]. PMID- 8510444 TI - [Tell me, what is that--death?]. PMID- 8510445 TI - [An educational model of hygiene]. PMID- 8510446 TI - [To understand, to consider ... and then to decide]. PMID- 8510447 TI - [Running as a therapeutic means. I. Running for health]. PMID- 8510448 TI - [The helping relationship in geriatric psychiatry. The tool of the future]. PMID- 8510450 TI - [The employee's obligation of care]. PMID- 8510449 TI - [Air pollution and health]. PMID- 8510451 TI - [Change of paradigm in nursing]. PMID- 8510452 TI - [How patients with a chronic disease learn--an inquiry. 1. Learning to remain independent]. PMID- 8510453 TI - [Study on foot reflex zone massage. Alternative to tablets]. PMID- 8510454 TI - [Concept on caring for students. Good care--optimal encouragement]. PMID- 8510455 TI - [A historical view of nursing. Notes on the history of history]. PMID- 8510456 TI - [Use of electrography. How to stabilize a bioenergetic balance]. PMID- 8510457 TI - Leading structures of plant origin for drug development. AB - This review summarizes the most important results of a plant screening program performed in the author's laboratory during the last 10 years. The screening program was initiated to search for new plant constituents with potential pharmacological activity in the field of inflammation in general, allergic asthma, immunodeficiencies and cardiovascular diseases. The test program mainly utilised in vitro assays, and particular attention was given to the key enzymes of the prostaglandin metabolism, cellular and humoral targets of the unspecific immune system, an in vitro ACE-inhibition test system, and an in vivo plethysmographic system as an inhibitory model of bronchial obstruction. The results of structure-activity relationship studies are also described. PMID- 8510458 TI - Mechanism of antiinflammatory actions of curcumine and boswellic acids. AB - Curcumine from Curcuma longa and the gum resin of Boswellia serrata, which were demonstrated to act as anti-inflammatories in in vivo animal models, were studied in a set of in vitro experiments in order to elucidate the mechanism of their beneficial effects. Curcumine inhibited the 5-lipoxygenase activity in rat peritoneal neutrophils as well as the 12-lipoxygenase and the cyclooxygenase activities in human platelets. In a cell free peroxidation system curcumine exerted strong antioxidative activity. Thus, its effects on the dioxygenases are probably due to its reducing capacity. Boswellic acids were isolated from the gum resin of Boswellia serrata and identified as the active principles. Boswellic acids inhibited the leukotriene synthesis via 5-lipoxygenase, but did not affect the 12-lipoxygenase and the cyclooxygenase activities. Additionally, boswellic acids did not impair the peroxidation of arachidonic acid by iron and ascorbate. The data suggest that boswellic acids are specific, non-redox inhibitors of leukotriene synthesis either interacting directly with 5-lipoxygenase or blocking its translocation. PMID- 8510459 TI - Botanical methods in ethnopharmacology and the need for conservation of medicinal plants. AB - An imperative demand imposed on all scientific investigations is that they should be repeatable, which calls for adequate documentation from the very beginning. In medicinal plant research, botanical documentation plays a vital role since without correctly identified material and properly documented voucher specimens the results are at best suspect and at worst useless. The botanical contributions required for ethnopharmacological research thus include adequate naming of the material and deposition of properly labelled voucher specimens in at least two public herbaria. Ethnopharmacology depends, however, upon botanical assistance also in another respect, viz. concerning conservation. This field may seem to have little to do with ethnopharmacology, but without joint efforts to save the useful plants from extinction, ethnopharmacology will lose important parts of its main source at an appalling rate. PMID- 8510460 TI - Plants in treating senile dementia in the northwest Amazon. AB - The Indians of the northwest Amazon respect age and try to care for those suffering from senile dementia. At least 25 species of plants are employed in treating Alzheimer's disease or similar problems. The plants are administered orally as teas of the leaves or roots and over a period of several days to numerous weeks. The plants are from 15 phanerogamic families. Little chemistry is known of most of the species. In view of the current interest in Alzheimer's disease and related problems these species might profitably be investigated. PMID- 8510461 TI - The status of ethnopharmacology in Brazil. AB - Brazil is a country of interest to ethnopharmacology because of its great wealth of cultural and biological diversity. This paper describes relevant research activities in the areas of botany, chemistry, basic and clinical pharmacology, and discusses the key factors that shaped ethnopharmacology development in the country. Specific attention is given to analyzing ongoing attempts to include medicinal plant based formulations in the official health care system. PMID- 8510462 TI - Ethnopharmacology and future drug development: the North American experience. AB - The major programs in North America designed to study plants as sources of potential drugs in which ethnomedical information is used to some extent are reviewed. Most of this work is carried out in academic laboratories in the United States; funded primarily from governmental agencies. A few major pharmaceutical companies in the United States are involved in drug development, using plants as sources of starting material, as well as many small start-up firms. These will be identified in the text with their major thrust, where known. Additionally, the NAPRALERT database on natural products will be described with the goal of illustrating how it may be used in the drug development process. Attenders at the Congress were given an opportunity to query the database on-line from Uppsala to Chicago. PMID- 8510463 TI - Pharmacognosy of Mimosa tenuiflora (Willd.) Poiret. AB - A chemical investigation of the bark of Mimosa tenuiflora (Willd.) Poiret, performed in our laboratory, allowed the isolation and identification of three new triterpenoid saponins (mimonosides A, B and C), three steroid saponins (3-O beta-D-glucopyranosyl campesterol, 3-O-beta-D-glucopyranosyl stigmasterol and 3-O beta-D-glucopyranosyl beta-sitosterol) together with lupeol, campesterol, stigmasterol and beta-sitosterol. The three new triterpenoid saponins were subjected to in vitro biological tests (immunomodulation and proliferation) using different animal and human cells in culture. The results of these tests contribute to explain the traditional use of this plant material. PMID- 8510464 TI - Chemical methods in ethnopharmacology. AB - The impact of improved spectroscopic techniques on structural elucidation is shown by examples from recent work on CNS active tiglianes from Pycnocoma cornuta Muell. The limited quantities of substance now needed for structural analysis can usually be obtained by routine high performance chromatography, but this methodology is less suited for large scale preparations. It may then be worthwhile also to consider earlier materials and methods. Particularly liquid liquid partitioning in old or new versions (CCC) may have advantages with respect to selectivity and mildness. In special cases activated carbon adsorbents may offer the benefits of selectivity and tolerance to high sample loads. PMID- 8510465 TI - Immunological aspects of Chinese medicinal plants as antiageing drugs. AB - The development of a predominantly geriatric community worldwide has become an inevitable fact. Antiageing agents could be, in a certain sense, attentive to the well-being of the aged. There are quite a lot of medicinal plants and prescriptions recorded in Chinese medical literatures aimed at the well-being of the aged as well as the prevention of diseases and prolongation of life-span. By means of modern scientific research, a strategy towards antiageing drugs is presented in this paper. One of the effective routes is to select the candidates based on their ethnopharmacological usages, followed by immunological investigation in connection with other antiageing experimentation. A list of Chinese medicinal plants used as or related to the antiageing agents are presented. Specifically, five Chinese traditional drugs, Herba Epimedii, Fructus Lycii, Radix Polygoni multiflori, Radix Cynanchi auriculati and Ganoderma along with a composite prescription 'American Ginseng Royal Jelly' are selected as representatives. The prospect of research and development of antiageing drugs based on natural origin is also discussed. PMID- 8510466 TI - Industrial development of traditional drugs: the forskolin example. A mini review. PMID- 8510467 TI - Saving the ethnopharmacological heritage of Samoa. AB - Early European visitors to Samoa tended to denigrate the authenticity and efficacy of Samoan herbal medicine, yet bioassays indicate pharmacological activity in over 86% of Samoan medicinal plants. Novel anti-inflammatory compounds have been isolated from Alphitonia zyzyphoides and Erythrina variegata, and the anti-HIV compound prostratin has been isolated from Homalanthus nutans. Unfortunately, both Samoan ethnopharmacology and Samoan rain forests are threatened. In order to prevent logging, funds were raised to build a needed village school in exchange for a village covenant to protect the 30,000 acre Falealupo forest. Subsequently, four additional rainforest reserves have been established. Hopefully such conservation measures can save the ethnopharmacological knowledge of Samoa. PMID- 8510468 TI - Methods in ethnopharmacology. AB - A variety of pharmacological models are utilized in the evaluation of ethnomedicine. Most investigations are focused on developing new leads for therapeutic agents. However, there should be more efforts focused on the development of ethnomedicines because of their accessibility and acceptability in areas where modern medicine is not readily available. Testing methods to identify the active agents must be carefully selected utilizing information from ethnoanthropology, ethnobotany, phytochemistry, toxicology and pharmacology. New pharmacological models focused on cellular and molecular mechanisms can be used for ethnomedical evaluations but with great caution since they are based on known mechanisms of actions and limited by knowledge of the disease state. PMID- 8510469 TI - An introduction to herbal pharmacoepidemiology. AB - Herbal pharmacoepidemiology concerns itself with herbal drug uses and effects in large numbers of people. This new methodology can make substantial contributions to our understanding of herbal drug markets. Not only can it improve the timely detection and the quantitation of adverse reactions to botanical medicines, it can also help us to recognize beneficial effects of herbal preparations. Moreover, it can increase our social and economic knowledge about herbal drugs by correlating the utilization patterns of these preparations to socially relevant determinants and prices. Since such studies may require an internationally accepted herbal drug classification, a special set of herbal classification codes is proposed, which is fully compatible with the so-called ATC-classification. This latter system is endorsed by the Regional Office for Europe of the World Health Organization as the drug classification to be used in international pharmacoepidemiological studies. PMID- 8510470 TI - Recent trends in research into African medicinal plants. AB - Recent trends in research into African medicinal plants show that while ethnobotanical surveys continue, there is an appreciable increase in research activity in the area of bioactivity of natural products. The biological areas most researched include antimicrobial, molluscicidal, toxicity tests and antitumour in decreasing order. The isolation and characterisation of natural products from African plants without biological testing has yielded several compounds of novel structure and constitutes the majority of all the recent publications on African medicinal plants. PMID- 8510471 TI - Search for antifungal, molluscicidal and larvicidal compounds from African medicinal plants. AB - African medicinal plants provide a rich source of biologically-active natural products. By the use of simple bioassays in conjunction with an approach involving bioactivity guided fractionation, it is possible to isolate novel compounds with interesting properties. Several hundred plant extracts have been submitted to different screens, including bioautography on TLC plates with the fungi Cladosporium cucumerinum and Candida albicans. Among the other test systems are a bioassay for molluscicidal activity with the schistosomiasis-transmitting snail Biomphalaria glabrata and a benchtop assay for larvicidal activity with larvae of the mosquito Aedes aegypti, the vector of yellow fever. Using a variety of modern separation techniques, a number of compounds with activity in these bioassays have been isolated. These include prenylated xanthones, tetracyclic phenols and saponins. The role of saponins and saponin-containing plants in the control of schistosomiasis is outlined. PMID- 8510472 TI - Research on pharmacologically active natural products at the Department of Pharmacognosy, Uppsala University. AB - Since 1954, research at the Department of Pharmacognosy at Uppsala University has been oriented towards modern natural products chemistry with emphasis on pharmacologically active compounds. Studies of plants used in the traditional medicine of different cultures have been of major interest. The research strategy is based on: inventory and identification of the plants used, demonstration of pharmacological activity of an extract of the plant, bioassay-guided fractionation, isolation and characterisation of the active compounds and studies of structure activity relationships. Plants from Africa, Asia, The Americas, The Pacific and Europe have been collected in collaboration with botanists and ethnobotanists. Investigations of these plants have resulted in the isolation, and chemical and pharmacological characterization of many different types of compounds. At present the work is focused on compounds with anti-inflammatory and immunomodulatory effects. PMID- 8510473 TI - Anthropological methods in ethnopharmacology. AB - This paper reviews anthropological methods in ethnopharmacology to advance a critical and biobehavioral perspective for the construction of primary data in the light of indigenous paradigms of health and therapeutics. The unique contributions of anthropology are the conceptual and practical tools that allow one to develop the ethnography of plant use in sufficient depth to correlate with laboratory and clinical investigations of plant constituents and activities. This serves an ethnopharmacology that links bioscientific research to traditional empirical knowledge. Specific methods discussed include: key respondents, participant observation, focus groups, structured and unstructured interviews, survey instruments and questionnaires, lexical and semantic studies, and discourse and content analysis. The accommodation of rapid ethnographic techniques for ethnopharmacologic research is described, and several problem orientations based on assessments of efficacy are offered. PMID- 8510474 TI - [The relationship between biliary lithiasis and lipoproteins isolated by ultracentrifugation]. AB - BACKGROUND: The prevalence of biliary lithiasis was studied in a sample of rural female population by calculation of the risk factors associated and the correlation between biliary lithiasis and serum lipoprotein concentrations. METHODS: Two hundred forty-nine women between the ages of 20-75 years in whom complete anamnesis and calculation of the Quetelet index (QI) were performed, were the subjects of this study. The investigation of biliary lithiasis was carried out by echography. Serum lipoprotein concentrations were determined by sequential ultracentrifugation. RESULTS: The prevalence of biliary lithiasis in the population studied was of 10.4%. A tendency to increase by age was observed and a peak between 50-60 years of age (p < 0.05) was registered. Biliary lithiasis was more frequent among the obese population (p < 0.05). With respect to lipoprotein parameters, all the lipid values of the different fractions demonstrated to be higher in the lithiasic population, although only the differences in cholesterol vehicled by very low density lipoproteins (C-VLDL) achieved statistical significance) (p < 0.001). CONCLUSIONS: The prevalence of biliary lithiasis in the female population studied is similar to that reported in other Western populations, and an increasing tendency in the prevalence of biliary lithiasis with age and obesity was observed. The levels of C-VLDL are higher in women with biliary lithiasis than in those without. PMID- 8510475 TI - [Prevalence of ischemic cardiopathy risk factors on the island of Lanzarote]. AB - BACKGROUND: As a fruit of complex interaction of factors, coronary atherosclerosis constitutes the first cause of death in the developed countries. METHODS: With the aim of studying the risk factors of ischemic cardiopathy in a natural adult population (30-64 years) from Lanzarote (Canary Islands) a representative sample of 600 individuals was studied with participation of 70% being obtained. RESULTS: The prevalences obtained were the following: established arterial hypertension (systolic: 160 mmHg and/or diastolic 95 mmHg) 24%; hypercholesterolemia (cholesterol: 6.5 mmol) 25%; diabetes (basal glucose: 7.8 mmol) 6.1%; hypertriglyceridemia (triglycerides 2.3 mmol) 12%; cholesterol (lipids and high density lipoproteinemia HDL) lower than 0.90 mmol in males 19% and lower than 1.16 mmol in females 36%; male smoking habit 53%; female smoking habit 15%; obesity (Quetelet index: 30) male 19%, females 35%, family history of ischemic cardiopathy (prior to 60 years of age) 14%; use of oral contraceptives in premenopausic females 13%; left ventricular growth in hypertensive individuals 7.4%. CONCLUSIONS: The prevalence of cardiovascular risk factors is high for arterial hypertension, diabetes, hypercholesterolemia, male smoking habit and female obesity. These results demonstrate an unfavorable profile for cardiovascular risk in the population of Lanzarote and it is reasonable to assume that this may be due to the great socioeconomic growth which has taken place on the island over the last decade. PMID- 8510476 TI - [The Prevalence of pain in hospitalized patients]. AB - BACKGROUND: There are few studies evaluating the presence of pain in hospitalized patients. Different authors have suggested interest in epidemiological studies to establish the characteristics of pain at a hospitalary level. The present study was initiated to determine the prevalence of pain in acute and chronic patients admitted to hospital and to establish the relation of the pain with the prescription of analgesics. METHODS: Pediatric, acute and chronic adult patients pertaining to a hospital in Sabadell (Barcelona) were included in the study. Patients from resuscitation, ICU, neonatology and the emergency wards were excluded. The variables studied were presence of pain and the existence of analgesic prescription. The first was determined by interview with the patient, while the second was obtained directly from the clinical history. RESULTS: Fifty five percent of the 217 adult patients with acute pathology manifest pain and in 45% of them total analgesics had been prescribed. The prevalence of pain was 61% among the 41 pediatric patients and 35% among the 98 adults with chronic disease. Prescription of analgesics was observed in 51 and 39%, respectively in the above groups of patients. The relation between the presence of pain and antialgic prescription was variable according to the groups. It must be emphasized that 50% of acute adult patients with pain did not have prescription of analgesics. Pain was present in all the pediatric patients with some analgesic prescribed. Sixty eight percent of the chronic patients with prescribed analgesics also experienced pain. CONCLUSIONS: The prevalence of pain in the hospital environment is high, not only in pediatric but also in adult and geriatric patients. The high number of patients who do not receive analgesics despite pain and those in whom the treatment does not totally eradicate the symptoms is of note. Analgesic therapy must acquire greater revelance in hospitalary assistance. PMID- 8510477 TI - [Lithos and lipids]. PMID- 8510478 TI - [What does cardiovascular risk factor mean?]. PMID- 8510480 TI - [Chronic fatigue syndrome: biologic and psychopathologic investigations]. PMID- 8510479 TI - [Importance of neurofibrillary degeneration in the diagnosis of Alzheimer's disease]. AB - For the pathological diagnosis of Alzheimer's disease ADRA-NIH recommend the quantification of plaques, without distinguishing their types, and neurofibrillary tangles. However, diffuse plaques may not be specifically associated to such diagnosis, as suggested by several authors and a previous paper. The neurofibrillary degeneration, present not only in neurofibrillary tangles but also in neuropil threads, either free in the neuropil or associated in plaques, could be more closely correlated with the decrease of cognitive functions than the plaques by themselves. In the present work, the efficiency of cholinesterase histochemical techniques and thioflavin-S is compared to the immunocytochemistry for abnormal tau, in two aspects: 1) the quantification of neurofibrillary degeneration, 2) the distribution of this degeneration, when present, within the plaques. It is concluded that immunocytochemistry for tau is the technique that better fulfills both goals, showing a better agreement with the cognitive state. For that reason tau immunocytochemistry is highly recommended in order to improve the anatomopathological diagnosis of Alzheimer's disease. PMID- 8510481 TI - [AIDS 1992. New definition, new classification]. PMID- 8510482 TI - [Medicamentous angioneurotic edema induced from quinapril]. PMID- 8510483 TI - [Neurologic alterations due to diclofenac]. PMID- 8510484 TI - [Melanoma and hypopigmentation]. PMID- 8510485 TI - [Double false negative tests in the localization of pheochromocytoma]. PMID- 8510486 TI - [Generalized lytic osseous lesions as a presenting feature of primary intestinal lymphoma]. PMID- 8510487 TI - Primary lymphoma of the liver. PMID- 8510488 TI - Effect of recombinant human transforming growth factor beta 1 on immune responses in patients with chronic hepatitis B. AB - Studies were undertaken to examine the effect of recombinant human transforming growth factor beta 1 (rTGF-beta 1) on cellular and humoral immune responses of peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis B. The addition of TGF-beta 1 caused a significant dose-dependent inhibition of hepatitis B (HB) core Ag-stimulated interferon-gamma and antibody to HB core Ag production and proliferation of PBMC from chronic hepatitis patients and HB immune donors. TGF-beta 1 also induced a significant reduction in pokeweed mitogen-stimulated IgG and IgM production, as well as phytohemagglutinin p stimulated proliferative response of PBMC. The degree of inhibition of TGF-beta 1 did not differ between antigen-specific and -nonspecific cellular and humoral immune responses, and between control individuals and patients. Pretreatment study with TGF-beta 1 showed that the activities of T cells, B cells and monocytes were similarly inhibited. Further, TGF-beta 1 inhibited activities of HLA class I antigen-matched cytotoxic T cells from patients with chronic hepatitis B for HBV DNA-transfected HepG2 cells in a 51Cr release assay. The results suggest that TGF-beta 1 may play a role in the regulation of antigen dependent and -independent immune responses in patients with chronic hepatitis B. PMID- 8510489 TI - Liver biopsy features of acute hepatitis C compared with hepatitis A, B, and non A, non-B, non-C. AB - The diagnosis of acute hepatitis C (AHC) often can only be suspected because current serologic tests remain negative for over 3 months. Because histologic features might provide useful clues, we reviewed 85 liver biopsy specimens from 85 patients with acute viral hepatitis, comparing 22 cases of AHC with 23 cases of acute hepatitis A (AHA), 30 cases of acute hepatitis B (AHB), and 10 cases of acute hepatitis non-A, non-B, non-C (AHNC). AHC was characterized by dense portal lymphoid aggregates (7 cases) and Poulsen-Christoffersen-type cholangitis (8 cases); these lesions were not found in any other type of acute viral hepatitis, and thus appeared to be diagnostic. Sinusoidal inflammatory infiltrates also were common in AHC, particularly in biopsy specimens obtained during the early phase of the disease. These inflammatory infiltrates did not appear to affect adjacent hepatocytes. Necrosis in AHC usually was spotty and accompanied by mixed inflammatory cells. In AHNC, necrosis was also spotty but, as an added feature, pigmented macrophages predominated in them. In AHA, necrosis was predominantly periportal, whereas in AHB, severe zone-3 necrosis predominated. Fatty changes were predominantly microvesicular; they were common in AHC but were also found in other groups. Collectively, the described histologic features allowed diagnosis of AHC in biopsy specimens with reasonable confidence. However, histologic findings failed to predict the prognosis in individual cases. PMID- 8510490 TI - Histological outcome of chronic hepatitis C treated with a 12-month course of lymphoblastoid alfa interferon. AB - To assess the effect of long-term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow-up (16.8 +/- 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 +/- 1.0, month 12: 1.6 +/- 1.1, p < 0.0001; lobular damage, month 0: 2.5 +/- 1.1, month 12: 1.4 +/- 0.9, p < 0.0001; portal inflammation, month 0: 3.6 +/- 0.5, month 12: 3.0 +/- 0.9, p < 0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to interferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the remaining cases. PMID- 8510492 TI - Effects of interferon-alpha treatment on hepatitis B virus antigen-specific immunologic responses in patients with chronic hepatitis B. AB - Studies were undertaken to evaluate the relationship between the immune responses and the effectiveness of interferon-alpha treatment in 21 patients with HBeAg positive chronic active hepatitis. Peripheral blood mononuclear cells (PBMC), obtained on four occasions during an 8-week course of IFN-alpha therapy, were cultured with recombinant HBcAg, purified HBeAg or pokeweed mitogen (PWM). During follow-up for 6 months after therapy, clearance of serum HBeAg was observed in eight patients designated as responders. Immunological responses of PBMC obtained before treatment did not differ between responders and non-responders. In responders, IFN-gamma and anti-HBc production was depressed during therapy, but recovered to above the pretreatment level at the end of and/or after cessation of therapy, while lymphocyte proliferation was enhanced during therapy with a subsequent decline to baseline value. In non-responders, such changes were modest throughout the study, and anti-HBc response remained decreased even after cessation of therapy. These results indicate that PBMC of responders have immunologically different responses to IFN-alpha therapy when compared with non responders. PMID- 8510491 TI - Hepatocyte-conditioned medium potentiates insulin-like growth factor (IGF) 1 and 2 stimulated DNA synthesis of cultured fat storing cells. AB - IGF-1 and IGF-2 stimulate dose-dependently DNA synthesis of nonconfluent cultures of rat fat storing cells, a nonparenchymal type of liver cells pathogenetically involved in the generation of liver fibrosis. Maximum stimulation of [3H] thymidine incorporation of about 2.6-fold above control was reached with 100 ng/ml IGF-1 and 500 ng/ml IGF-2, respectively. The DNA synthesis promoting action of both IGF-1 and IGF-2 was most efficiently potentiated by hepatocyte conditioned medium raising the stimulatory effect up to 21-fold above control cultures. Lysate of hepatocytes (up to 15 micrograms protein/ml) was not effective in potentiating the effect of IGF-1. IGF-1 is bound to free carrier protein(s) present in the medium of hepatocytes, but obviously absent in cell lysate. Three molecular weight fractions in the ranges of 67 kd, 35 kd, and 25 kd could be identified in the medium, which potentiate the growth-promoting effect of IGF-1. Applying Western ligand blot analysis, three molecular size classes of IGF-1 binding proteins in the conditioned media of rat hepatocytes were determined. The major binding protein had a M(r) of 28-34 kd, a minor portion was localized at M(r) 24 kd, whereas trace binding affinities were found at M(r) of about 95 kd. It is suggested that IGF-1, IGF-2 and the complex array of IGF binding proteins secreted by hepatocytes might be involved in the paracrine regulation of growth of fat storing cells. PMID- 8510493 TI - Differences in c-fos immunoreactivity due to age and mode of seizure induction. AB - The aim of this study was to determine whether the regional distribution and time course of immunoreactivity to the c-fos protein varies with maturation and method of seizure induction. The effect of the two chemical convulsants, pentylenetetrazol (PTZ) and flurothyl, on the spatial and temporal pattern of c fos-like immunoreactivity in immature (postnatal day (P) 10) was compared to that in adult rats. Patterns of c-fos-like immunoreactivity following O2 deprivation were also evaluated at the 2 ages because hypoxia is acutely epileptogenic in immature animals but not adults. C-fos-like immunoreactivity was examined at 2, 4, and 6 h after onset of chemically induced seizures or O2 deprivation at both ages. After PTZ or flurothyl seizures, both ages exhibited similar patterns of IR in amygdala, pyriform cortex, and hypothalamus. Age-dependent regional differences were most prominent in cortex: superficial layers of retrosplenial, cingulate, and neocortex stained in adults; staining was confined to deep layers of neocortex in P10 rats. Intense staining of dentate gyrus and hippocampus occurred with more prolonged seizures, but not brief seizures. PTZ administration resulted in staining at 2 h after seizure onset and was reduced by 4 h in adults, but immunoreactivity was not seen until 4 and 6 h after seizure onset in immature rats, indicating an age effect on the time course of IR. In immature rats, immunoreactivity patterns after hypoxia were markedly different from PTZ or flurothyl: staining was confined to layer VI of neocortex in these animals, and rarely involved limbic structures. These differences in the pattern of c-fos immunoreactivity suggest that the neuronal populations involved in epileptogenesis are influenced by age as well as seizure phenotype and intensity. PMID- 8510494 TI - Analysis of the promoter sequence and the transcription initiation site of the mouse 5-HT1C serotonin receptor gene. AB - The serotonin 1c (5-HT1C) receptor is found in many brain regions, but is particularly enriched on the epithelial cells of the choroid plexus. A major challenge in neurobiology is to delineate the molecular processes that regulate the specific pattern of neuronal gene expression in the brain. As an initial step towards identifying cis-acting DNA sequences that control the expression of the 5 HT1C receptor, we have isolated the promoter sequence of its gene. Sequence analysis of a 1.8 kb fragment indicated that the 3' end of this fragment overlaps with the 5' untranslated region of the 5-HT1C receptor mRNA, and primer extension using mouse brain poly(A)+ RNA mapped the transcription initiation site within this fragment. There are a number of sequence elements upstream from the transcription initiation site that are homologous to regulatory elements found in other eucaryotic genes. To determine the promoter activity, a plasmid was constructed that contains this fragment as promoter region and the cDNA for the 5 HT1C receptor as the reporter. When injected into the nucleus of Xenopus oocytes, this construct resulted in functional expression of the reporter gene. Primer extension using the RNA extracted from the injected oocytes indicated a single transcription initiation site of the reporter mRNA. These results suggest that the 5-HT1C receptor was functionally expressed under the promoter activity of the 1.8 kb 5' sequence of its gene. This system will be useful for further analysis of the cis-acting elements in the promoter region of the 5-HT1C receptor gene and the trans-acting factors that regulate tissue-specific expression of the receptor. PMID- 8510495 TI - Distinct NCAM splicing events are differentially regulated during rat brain development. AB - Primary transcripts for the neural cell adhesion molecule NCAM are highly alternatively spliced potentially giving rise to over 100 different mRNA forms. These mRNAs encode three major polypeptide isoforms of 120, 140, and 180 kDa each of which is thought to be composed of a mixture of polypeptides that differ by the variable presence of small exons at two locations. These NCAM 'microsplicing' patterns were examined within mRNA populations encoding each of the major isoforms to identify exactly which NCAM forms are present during brain development. The proportion of NCAM mRNAs containing at the exon 7/8 junction the alternatively microspliced 30 bp VASE exon increased similarly during brain development in mRNAs encoding all three major size classes. Perinatal brain, cultures of neurons from embryonic rats, and of glia from newborn rats all had low VASE levels while about 50% of the mRNAs in adult brain expressed VASE. In contrast, microsplicing at the exon 12/exon 13 junction was differentially regulated among NCAM major size classes. mRNAs containing microspliced exons totaling 3.15, or 18 base pairs (bp) represented greater than 50% of the total mRNAs encoding the 120 kDa forms at all ages. However, these exons were present in less than 15% of the 140 and 180 kDa encoding mRNAs in rats older than embryonic day 15. Similar results at the exon 12/13 junction were observed with mRNAs from neuronal cultures while glial cultures had greater levels of a 3 bp pair exon at this junction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510496 TI - Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy. AB - Expression of mRNAs for the protein tyrosine kinases trk, trkB and trkC, encoding essential components of high-affinity neurotrophin receptors, was studied in the spinal cord and dorsal root ganglion during normal development and in the adult rat following peripheral and central axon injury. Northern blots revealed multiple trkB transcripts in the embryonic, early postnatal and adult spinal cord with different patterns of expression during development. The levels of 9.0 kb and 4.8 kb trkB transcripts, encoding a full-length trkB receptor, increased progressively during embryonic development with maximal levels around birth, followed by a decline at adulthood. In contrast, the level of 7.5/7.0 kb trkB transcripts, encoding a truncated trkB receptor, reached maximal levels shortly after birth and similar levels remained in the adult animal. In the spinal cord a 4.7kb trkC transcript was detected with maximal levels shortly after birth. In situ hybridization revealed a uniform labeling throughout the spinal cord for both trkB and trkC mRNAs with maximal intensities of labeling shortly after birth. The level of the 2.4 kb trkB transcript in the spinal cord increased 5 fold 8 days after a crush lesion of the sciatic nerve or the dorsal root, while no change was seen in the levels of the other trkB transcripts. No change in the 4.7 kb trkC mRNA was seen following these two injuries, although increased levels of several smaller size trkC transcripts were observed. For both trkB and trkC, similar size transcripts as seen in the spinal cord were also detected in adult rat dorsal root ganglia. Consistent with previous observations of decreased levels of cytoskeletal proteins after peripheral and central axotomy, the level of neurofilment light chain mRNA decreased markedly in the dorsal root ganglia following a crush lesion of the sciatic nerve or of the dorsal root. A small decrease was also seen in the level of preprotachykinin-A mRNA encoding the protein precursor of substance P. In the same animals, the levels of all five trkB transcripts increased 3-fold in the dorsal root ganglia in response to these two injuries. A small increase was also seen in the level of trkC mRNA. The level of brain-derived neurotrophic factor (BDNF) mRNA increased two-fold in the dorsal root ganglia following either of the two lesions, while no change was detected in trk mRNA following these two injuries.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510497 TI - Identification of a neuron-specific promoter of human aromatic L-amino acid decarboxylase gene. AB - We have cloned the 5' region of human aromatic L-amino acid decarboxylase (AADC) gene in a cosmid and an overlapping lambda clone, and sequenced the first five exons. A 61 base pair (bp) non-coding, first exon containing for the 5' end of a human pheochromocytoma AADC cDNA was localized 16 kb upstream of exon 2, in which translation is initiated. The transcription start site was localized by RNAse mapping, primer extension and reverse transcription-PCR. The non-conventional cap site was preceded by a modified TATA box at position -29. A strong promoter was characterized in the 560 bp region upstream of the cap site by linkage to the reporter gene LacZ, and transfection in human neuroblastoma SK-N-BE and SK-N-BE K2 cells. Using a series of constructs bearing a varying length of 5' flanking region, three positive regulatory elements have been localized in the -560 to 394, -244 to -200 and -147 to -1 regions. Negative regulatory elements were localized in the -9000 to -560 and -394 to -316 regions. Surprisingly, constructs comprising all or the major part of intron 1 were inactive, suggesting the presence of a silencer in the first intron, or incorrect splicing events. The construct containing 560 bp of 5' flanking sequence did not express in human cholinergic neuroepithelioma cells MC-I-XC, and in three non-neuronal cell lines which displayed high AADC activities: human pancreatic carcinoma cells AsPC-1, rat insulinoma cells RINm5F and mouse anterior pituitary cells AtT20. These data suggest that we have identified a neuron-specific AADC promoter. An extensive search for a second promoter responsible for AADC gene expression in non-neuronal cells only gave negative results. PMID- 8510498 TI - The 5'-flanking region of the human dopamine beta-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice. AB - Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) catalyzes the conversion of dopamine to norepinephrine, the third step of catecholamine biosynthesis. We have previously created transgenic mice harboring a chimeric gene consisting of the 4 kb DNA fragment of the human DBH gene promoter and the human phenylethanolamine N methyltransferase (PNMT, EC 2.1.1.28) cDNA, to express PNMT in norepinephrine- and epinephrine-producing cells in the brain, sympathetic ganglia, and adrenal medullary chromaffin cells (Kobayashi et al., Proc. Natl. Acad. Sci. U.S.A., 89 (1992) 1631-1635). In this paper, we produced for the first time the antibody that specifically detects human PNMT, but not mouse PNMT, with the synthetic oligopeptide characteristic of the human PNMT sequence, and used this antibody to investigate the cells expressing human PNMT in transgenic mice. Immunohistochemical analysis of transgenic mice showed typical expression of human PNMT immunoreactivity in norepinephrinergic and epinephrinergic neurons in brain, as well as norepinephrine- and epinephrine-producing cells in the adrenal gland, indicating that the 4-kb 5'-flanking region is essential for the tissue specific expression of the DBH gene. We also detected the ectopic expression in some DBH-immunonegative cells in the olfactory bulb of transgenic mice. PMID- 8510499 TI - Methylation and expression of neurofilament genes in tissues and in cell lines of the mouse. AB - The light (NF-L), mid-sized (NF-M) and heavy (NF-H) neurofilament (NF) genes were probed with methylation-sensitive restriction enzymes and patterns of methylation and expression of the NF genes were compared in tissues and cell lines of the mouse. The 5' regions of all three NF genes are identified as CpG islands that remain unmethylated in expressing and non-expressing tissues, although partial methylation occurs at -795 in NF-H and at -525 in NF-M. Methylation of the NF CpG islands is associated with the inactivation of NF genes in L cells and with the selective inactivation of NF-L and NF-M in Neuro 2a cells. We also show that methylation diminishes the ability of the NF promoters to drive transcription of a CAT reporter gene. Hence, the presence of CpG islands may be important in determining patterns of NF transcription in vitro. Moreover, the preservation of CpG islands may be an evolutionary link that bears upon the nature of the NF genes and the mechanisms that have evolved to limit NF expression. PMID- 8510500 TI - Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. AB - The pattern of expression of fos and jun family immediate early genes following the induction of long-term potentiation (LTP) was investigated in the dentate gyrus of awake rats. Rapid, transient increases in the levels of c-jun and jun-B mRNA and protein, and in the levels of Fos-related proteins (FRAs), occurred in the dentate gyrus after LTP-inducing tetanization of the perforant path. A delayed, and more prolonged induction occurred for jun-D mRNA and protein. The induction of c-Jun, Jun-B, Jun-D and Fos-related proteins was prevented by administration of an N-methyl-D-aspartate receptor antagonist, which also blocked LTP induction, and by pentobarbital, which reduced but did not block LTP. These findings show that differential expression of fos and jun gene family members occurs in a distinct pattern following LTP in awake rats. The responsive genes may participate in the biochemical cascade leading to the long-term stabilization of synaptic modifications. PMID- 8510501 TI - Induction of F1/GAP-43 gene expression in hippocampal granule cells after seizures [corrected]. AB - In the adult rat hippocampus mRNA of F1/GAP-43, an axonal growth-associated protein, is highly expressed in pyramidal cells, but is absent in granule cells. To determine whether granule cells can be induced to express mRNA of F1/GAP-43, transcript levels were studied after limbic seizures, which can induce sprouting of granule cell mossy fibers. Seizure-inducing electrolytic lesions were made in the dentate gyrus hilus with stainless-steel electrodes and mRNA levels were measured in contralateral hippocampus by quantitative in situ hybridization. Induction of F1/GAP-43 mRNA expression was observed in granule cells at 24 h, but not at 6 or 12 h, after the hilar lesion. When equivalent sized hilar lesions were made with platinum electrodes, which do not induce seizures, no hybridization was apparent over the granule cells. Hybridization over granule cells had declined by 48 h post-lesion, but even at 10 days it was still slightly higher than in control rats. F1/GAP-43 mRNA expression was also increased 2-fold in CA1 pyramidal cells with peak expression at 48 h post-lesion. These are the first data to our knowledge that demonstrate that F1/GAP-43 gene expression can be altered in neurons located within the adult brain. Induction of F1/GAP-43 mRNA expression in the granule cells may be important for the sprouting of mossy fibers and could be triggered by the elevated levels of brain-derived neurotrophic factor in CA3 cells which precede the increased F1/GAP-43 gene expression in granule cells. PMID- 8510502 TI - Expression of Egr-1 in the brain of sleep deprived rats. AB - In previous research, rats subjected to prolonged sleep deprivation have shown disturbances of thermoregulation, hormonal and metabolic changes in apparent response to the thermoregulatory problems, lesions on the tail and paws, and eventual death. To search for alterations of functional activity in brain, the expression of the immediate early gene Egr-1 was examined by immunocytochemistry and Northern blotting in rats subjected to total sleep deprivation (TSD) for 10 days. Controls included yoked stimulus-control (TSC) rats, surgically implanted but otherwise undisturbed control rats, and unoperated control rats. Photographs of immunoreacted coronal sections from four sets of rats were ranked blindly for 25 brain regions. TSD rats showed tendencies for regionally specific increases in Egr-1-like immunoreactivity in dorsal raphe, lateral habenula, superior colliculus, and ventral periaqueductal grey. However, most regions showed no differences in Egr-1-like immunoreactivity between TSD and control rats. Neither was there a difference in whole brain Egr-1 mRNA by Northern blot in two additional sets of rats. Thus, this study, like previous studies of brain histology, amines, adrenoceptors, and glucose utilization, does not provide positive support for the hypothesis that sleep protects the central nervous system against massive global damage, fatigue, or dysfunction. PMID- 8510503 TI - Early opsin expression in Xenopus embryos precedes photoreceptor differentiation. AB - The visual pigment which serves as the first step in the phototransduction cycle in vertebrate rod cells consists of a retinal chromophore which is linked to the transmembrane protein, opsin. Opsin genes have been isolated from a number of different organisms and studies have shown opsin to be developmentally regulated with both mRNA and protein expression associated with the morphological differentiation of photoreceptor cells. Due to its potential utility as a marker for rod photoreceptor determination in studies of retinal tissue interactions, and because no amphibian opsin genes have as yet been cloned, we isolated cDNA clones of the Xenopus laevis opsin gene. Sequence analysis shows that within the coding region Xenopus opsin shares a high degree of identity with other rod opsin genes, except at the C-terminal where it more closely resembles the mammalian color opsins. A developmental analysis, on the other hand, reveals that Xenopus opsin transcripts are detectable in a retina-specific fashion early in retinal development. Using in situ hybridization we find that Xenopus opsin mRNA is initially restricted to a few isolated cells in the presumptive photoreceptor layer which express the gene at relatively high levels. This suggests that rod photoreceptor determination occurs in single cells, and that the mechanisms controlling opsin expression in Xenopus are initiated well before any evidence of morphological differentiation. PMID- 8510504 TI - NGF deprivation and neuronal degeneration trigger altered beta-amyloid precursor protein gene expression in the rat superior cervical ganglia in vivo and in vitro. AB - In order to study the expression of beta-amyloid precursor protein (APP) isoforms during neuronal degeneration we have used the rat superior cervical ganglia (SCG) as an experimental model. In the neonate these sympathetic ganglia are nerve growth factor (NGF) dependent and in vivo administration of anti-NGF antiserum results in exaggerated neuronal degeneration. Analysis of APP mRNA transcripts in the SCG, following NGF deprivation, revealed a coincident decrease in APP695 and augmentation of APP751/770. These changes were specific to the SCG and were not seen in sensory ganglia. Subsequent in vitro studies, using primary dissociated cultures of sympathetic or cortical neurones, confirmed these changes in APP gene expression during neuronal degeneration. These observations may have important implications for the generation of beta-amyloid in Alzheimer's disease. PMID- 8510505 TI - Expression of muscarinic and nicotinic receptor mRNA in the salivary gland of rats: a study by in situ hybridization histochemistry. AB - Expression of muscarinic receptor mRNA subtypes (m1-5) and nicotinic receptor subunits (alpha 2-4, and beta 2) was examined in the rat submandibular gland by in situ hybridization histochemistry, using oligonucleotide probes for the muscarinic receptor and RNA probes for the nicotinic receptors. m2, alpha 3, and beta 2 mRNA were strongly expressed in the submandibular ganglion, and m3, alpha 2, alpha 3, alpha 4, and beta 2 were expressed in the striated and interlobular duct cells. Both muscarinic and nicotinic receptors were coexpressed in the same ganglion neurons, while none of these mRNA were detected in the terminal secretory units. PMID- 8510506 TI - Regional distribution of the alternatively spliced isoforms of beta APP RNA transcript in the brain of normal, heterozygous and homozygous weaver mutant mice as revealed by in situ hybridization histochemistry. AB - The cellular localization of amyloid beta-protein precursor (beta APP) RNA transcripts was studied by in situ hybridization histochemistry in normal, heterozygous and homozygous weaver (wv) mutant mice, which lose midbrain dopamine (DA) neurons, cerebellar granule cells, and Purkinje cells. The beta APP gene is located at the distal end of mouse chromosome (MMU) 16, on which the wv locus has been assigned as well. Transcripts encoding isoforms beta APP695, beta APP714 and beta APP751 were present in several different brain areas of normal (+/+) mice, including hippocampus, substantia nigra (SN) pars compacta and cerebellum. The same transcripts were progressively reduced in homozygous weaver (wv/wv) SN, in correlation with DA neuron loss. The beta APP770 species--normally seen in striatum and not SN--was present in the mutant striatum. There were not any obvious changes in beta APP expression in the nigrostriatal system of weaver heterozygotes (wv/+). In normal cerebellum, Purkinje cells showed very high levels of hybridization signal for beta APP695, beta APP714 and beta APP751 RNA transcripts, and a moderate signal for the beta APP770 species. In weaver heterozygotes and homozygotes, Purkinje cells, which are typically not arranged in a monolayer, showed strong hybridization signal. No changes in beta APP mRNAs were observed in brain areas other than the cerebellum and ventral midbrain of weaver mutants. These findings suggest that the decreased beta APP gene expression seen in the cerebellum and SN of weaver mutants most likely represents an epiphenomenon of the regional nerve cell loss and, therefore, the wv gene defect on MMU 16 does not seem to influence the expression of the closely linked beta APP gene in brain areas outside the nigrostriatal pathway and cerebellar cortex. PMID- 8510507 TI - Staffing of mental health organizations, United States, 1988. AB - Between 1986 and 1988, the number of full-time equivalent (FTE) staff employed in specialty mental health organizations in the United States increased 7 percent, from 494,515 to 531,067. Much of this increase could probably be attributed to the increase in number of mental health organizations during this period, from 4,747 to 4,930. With the exception of State mental hospitals and VA psychiatric organizations, all of the other types of mental health organizations showed varying amounts of increase in FTE staff with the most notable gains being reported by private psychiatric hospitals, residential treatment centers for emotionally disturbed children, and multiservice mental health organizations. Of the 531,067 FTE staff employed in mental health organizations in 1988, 72 percent were classified as patient care staff and 28 percent as administrative and support staff. State mental hospitals and VA psychiatric organizations had slightly higher percentages of administrative and support staff (35 and 32 percent, respectively). Seventy percent or more of the staff employed in the various types of specialty mental health organizations in 1988 worked on a full time basis, the two exceptions being freestanding psychiatric outpatient clinics and non-Federal general hospital psychiatric services in which full-time staff represented only 52 percent and 69 percent, respectively, of all staff. For the most part, the majority (50 percent or more) of each of the staff disciplines employed in mental health organizations worked on a full-time basis. The major exceptions were psychiatrists and other physicians, most of whom worked either on a part-time or trainee basis. PMID- 8510508 TI - Growth hormone normalizes hepatic lipase in hypothyroid rat liver. AB - The effects of growth hormone (GH) administration on hepatic lipase (HL) activity and mRNA levels were studied in pair-fed hypothyroid rats. In the hypothyroid state, liver HL mRNA levels and liver and postheparin plasma HL activities were decreased. In hypothyroid rats, GH normalized HL mRNA levels and HL activity in postheparin plasma; GH also increased the activity of HL in the liver, which remained lower than that in controls. These data indicate that at least part of the decrease of HL activity during hypothyroidism is due to the concomitant GH deficiency, and that GH rather than thyroid hormone may regulate HL mRNA levels. PMID- 8510509 TI - Effect of 17 beta-estradiol on secretion of platelet-activating factor acetylhydrolase by HepG2 cells. AB - Estrogen has been shown to decrease plasma platelet-activating factor (PAF) acetylhydrolase activity, but the precise mechanisms are not known. We examined the effect of estradiol on the secretion of PAF acetylhydrolase by HepG2 cells. In our previous study, we demonstrated the production of this enzyme by HepG2 cells, which we used as an experimental model of normal hepatocytes. 17 beta Estradiol mildly but consistently inhibited the secretion of PAF acetylhydrolase by HepG2 cells in a concentration-dependent manner. Under basal conditions, HepG2 cells secreted 42.3 pmol/mg cell protein/min PAF acetylhydrolase in 24 hours (mean of 8 dishes), and the presence of 10(-7) mol/L 17 beta-estradiol decreased the secretion to 77% +/- 10.3% of control values (mean +/- SD, n = 8, P < .02). 17 beta-Estradiol treatment affected neither the secretion of apolipoprotein (apo) A-I nor cell-associated PAF acetylhydrolase activity. Electrophoretic separation of [35S]methionine-labeled PAF acetylhydrolase revealed a single band whose molecular weight was approximately 43,000 d. We conclude that estrogen decreases the secretion of PAF acetylhydrolase by the liver, and it may explain, at least in part, the effect of estrogen on plasma PAF acetylhydrolase. PMID- 8510510 TI - Low-density lipoprotein metabolism in rats treated with cyclosporine. AB - Metabolic mechanisms underlying the observations of elevated cholesterol concentration of low-density lipoprotein (LDL) in organ-transplanted patients on long-term immunosuppressant cyclosporine therapy were explored using cyclosporine treated rats as an experimental model. As in patients, treatment with cyclosporine induced a significant elevation of plasma cholesterol level, mainly in LDL cholesterol, with a decrease in high-density lipoprotein (HDL) cholesterol level. In an in vivo cross-over study design, differentially radioiodinated homologous LDL from donor cyclosporine-treated rats (Cyc-LDL) and excipient-only treated control rats (Exc-LDL) were injected into recipient cyclosporine-treated rats (Cyc-rats), excipient-only--treated control rats (Exc-rats), and untreated rats (Unt-rats). From the isotope disappearance curves, the fractional catabolic rate (FCR) and production rate were calculated. The results showed that FCR and production rate were significantly reduced in Cyc-rats compared with control Exc rats and Unt-rats. The decrease was independent of the donor LDL source. In vitro LDL ligand-receptor assays indicated a twofold higher degradation of Cyc-LDL by cultured rat fibroblasts, and hence could not account for the decreased clearance observed in vivo. These results suggest that the elevated concentrations of LDL cholesterol associated with cyclosporine treatment result not from a cyclosporine induced modification of the LDL molecule, which could diminish its receptor mediated clearance/catabolism, but possibly from an in vivo pharmacological property of cyclosporine such as an induced hepatic dysfunction. PMID- 8510511 TI - Increased reverse cholesterol transport in athletes. AB - Proposed mechanisms for the cardioprotective benefits of exercise include decreased lipid deposition and increased reverse cholesterol transport (RCT). RCT involves the efflux of tissue free cholesterol into high-density lipoprotein (HDL) particles, esterification by lecithin:cholesterol acyltransferase (LCAT), transfer to other lipoproteins by cholesterol ester transfer proteins (CETP), and liver excretion. We tested the hypothesis that RCT is enhanced in athletes and that this can occur without large increases in plasma HDL cholesterol (HDL-C) mass levels. Fasting venous blood was drawn from 13 sedentary men and 11 athletes exercising at the rate of 5,185 +/- 501 kcal/wk. Compared with controls, athletes had similar age, body mass index (BMI), HDL-C (P > .1) and apolipoprotein (apo) A 1 (P > .5) levels, and lower low-density lipoprotein cholesterol (LDL-C) (P < .05) and apo B (P < .03) levels. The net mass of free cholesterol transported (NMCT) out of cultured human fibroblasts into the athletes' serum was greater than that for controls (25.5 +/- 8.0 v 7.1 +/- 2.6 micrograms/mL/h, P = .048). The efflux component of this transport correlated with HDL-C and apo A-1 levels and was similar between groups (P = .24), suggesting that athletes' antiatherogenic NMCT findings were due to decreased cholesterol influx into the cells. Athletes had increased plasma LCAT (20.3 +/- 2.1 v 13.9 +/- 1.5 micrograms/mL/h, P = .028) and CETP activities (69.7 +/- 4.5 v 21.5 +/- 4.8%/mL/h, P < .001). The NMCT positively correlated with CETP and LCAT activities and inversely with apo B levels and the cardiac risk ratio apo B/A 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510512 TI - Comparison of precursor pools with leucine, alpha-ketoisocaproate, and phenylalanine tracers used to measure splanchnic protein synthesis in man. AB - Relationships were determined between the labeling of leucine and phenylalanine at the intracellular site of protein synthesis in the pancreas and labeling of plasma leucine, its keto acid, alpha-ketoisocaproate (KIC), and phenylalanine. Six healthy subjects were studied for 480 minutes during a primed constant infusion of [1-14C]leucine, and six healthy subjects were studied for 240 minutes with [1-14C]leucine, [4,5-3H]phenylalanine, and [1-13C]KIC. An oro-duodenal tube was placed and pancreatic exocrine fluid was sampled by duodenal aspiration during cholecystokinin stimulation. During the 480-minute study, in the final 120 minutes the specific activity (SA) of enzyme leucine (3.14 +/- 0.27 dpm/nmol) was lower than that of plasma leucine (4.18 +/- 0.30 dpm/nmol, P < .001), but was not different from that of plasma KIC (3.02 +/- 0.18 dpm/nmol). During the 240-minute study, protein synthesis rates of secreted pancreatic enzymes when calculated with [3H]phenylalanine were lower (P = .006) by 28% +/- 2% than rates based on [14C]KIC SA, and lower (P = .004) by 16% +/- 3% than those calculated using [14C]leucine SA. Incorporation of [13C]leucine into pancreatic enzymes was not different from that of [14C]leucine when [13C]leucine and [14C]KIC, respectively, were used to denote precursor labeling. The results indicate that plasma KIC SA reflects the precursor pool for pancreatic protein synthesis during leucine tracer infusion, and plasma leucine enrichment also reflects the precursor pool when [1-13C]KIC is infused in man. The precursor pool is erroneously overestimated when using plasma SA of [4,5-3H]phenylalanine or [1-14C]leucine. PMID- 8510513 TI - Alterations in plasma alpha- and gamma-tocopherol concentrations in response to intravenous infusion of lipid emulsions in humans. AB - To study the fate of intravenously infused vitamin E, we infused lipid emulsions rich in gamma-tocopherol (Intralipid, Kabi, Stockholm, Sweden), or in both alpha- and gamma-tocopherols (Lipidem, Hausmann Laboratories, St Gallen, Switzerland); in normal human volunteers. Plasma gamma-tocopherol levels increased in four subjects infused with Intralipid 10% (0.3 g triglyceride [TG]/kg/h for 6 hours) from 3 +/- 1 to 25 +/- 2 nmol/mL, but by 24 hours they decreased to 5 +/- 1 nmol/mL. Although eight times more gamma-tocopherol was infused, plasma alpha tocopherol levels also increased from 26 +/- 7 to 39 +/- 9 nmol/mL at 8 hours and decreased to 24 +/- 5 nmol/mL at 24 hours. Increases of alpha-tocopherol in the very-low-density lipoprotein (VLDL) density range occurred at 6 and 8 hours, while decreases occurred in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) density ranges at 3, 6, 8, and 24 hours. Infusion of both emulsions in random order to six subjects at therapeutic rates (0.1 g/kg/h for 6 hours) resulted in (1) a threefold increase in plasma gamma-tocopherol concentrations at 6 hours, (2) increases in plasma alpha-tocopherol concentrations only with Lipidem (from 14.3 +/- 1.0 nmol/mL at 0 hours to 18.4 +/ 2.7 at 6 hours and 18.9 +/- 1.1 at 24 hours), and (3) no decreases in lipoprotein alpha-tocopherol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510514 TI - Dose-dependency of the glycemic response to starch-rich meals in insulin dependent diabetic subjects: studies at constant insulinemia. AB - The study objective was to determine the dose-response relationship of postprandial blood glucose response areas to the amount of starch ingested in insulin-dependent diabetic (IDDM) subjects. Three test meals were served in random order with a 7-day interval to seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital. Mixed meals of 23, 46, and 69 g parboiled white rice (raw weight) containing approximately 20, 40, and 60 g available carbohydrate were served cooked on three separate days. The patients had achieved normoglycemic blood glucose levels 2 hours before meal intake by means of an artificial pancreas (Biostator, Miles Laboratories, Elkhart, IN), which also provided constant insulin infusion during the study periods (0 to 180 minutes). A clear-cut dose-response relationship between the amount of starch ingested and postprandial peak blood glucose values (r = .96) as well as glucose response areas (r = .99) was found. Glucose response areas to meals containing 20, 40, and 60 g carbohydrate differed significantly (P < .01), attaining 291 +/- 77, 643 +/- 75, and 878 +/- 99 mmol/L x 180 minutes, respectively. Glucosuria accounted for 0.6 and 1.6 g (NS) after 20 and 40 g carbohydrate, whereas 5.0 g glucose (P < .05) was detected following 60 g carbohydrate. Similar mean serum free insulin levels (range, 102 to 150 pmol/L) during the three study periods were found. PMID- 8510515 TI - The role of cholesterol absorption and hepatic cholesterol content in high and low responses to dietary cholesterol and fat in pedigreed baboons (Papio species). AB - Selective breeding has produced baboon families with low and high plasma cholesterol responses to dietary cholesterol and fat. We used 12 high- and 12 low responding (mainly in low-density lipoprotein [LDL] cholesterol) pedigreed baboons to determine whether cholesterol absorption and hepatic cholesterol concentration are associated with these responses. We measured cholesterol absorption first on the chow diet, which was low in cholesterol and fat, and after 3 and 13 weeks on the challenge diets, which contained 0.45 mg cholesterol/kcal and 40% of calories as either coconut oil or corn oil. Plasma, lipoprotein, and hepatic cholesterol concentrations were measured 1 week after cholesterol absorption measurements. High-responding baboons had higher percentage cholesterol absorption than low-responding baboons on both chow and challenge diets, regardless of the type of dietary fat. Both high and low responders had higher percentage cholesterol absorption with corn oil than with coconut oil. High responders also had higher hepatic cholesterol concentrations than low responders on chow and after consuming the challenge diets for 4 weeks. After consuming the challenge diets for 14 weeks, low responders fed coconut oil had hepatic cholesterol levels equal to those of high responders, while low responders fed corn oil continued to have low hepatic cholesterol levels. Thus, percentage cholesterol absorption is consistently higher in high-responding baboons regardless of diet, but hepatic cholesterol concentration varies with duration of challenge and type of fat. The results suggest that both cholesterol absorption and hepatic cholesterol concentration regulate cholesterolemic responses to diet, but by different mechanisms. PMID- 8510516 TI - Norepinephrine turnover and energy expenditure in Pima Indian and white men. AB - There is growing evidence of the involvement of sympathetic nervous system (SNS) activity in determining metabolic rate. Whole-body plasma norepinephrine turnover and its relationship to resting metabolic rate (RMR) and 24-hour energy expenditure (24EE) were compared in 14 Pima Indian men (25 +/- 4 years, 96 +/- 33 kg, 25% +/- 9% fat) and nine white men (25 +/- 3 years, 88 +/- 43 kg, 17% +/- 13% fat). Plasma norepinephrine turnover rate correlated strongly with body surface area (r = .76 and .54 for clearance and appearance, respectively) and fat-free mass (r = .74 and .52, respectively). However, independent of body size, there was no difference in either norepinephrine clearance or appearance rates between Pima Indian and white men. Norepinephrine appearance rate correlated positively with absolute values of 24EE and RMR, but not when adjusted for differences in body surface area or fat-free mass. However, norepinephrine appearance rate adjusted for differences in body size correlated with spontaneous physical activity. The results indicate that Pima Indian and white men have similar plasma norepinephrine appearance rates, but Pima Indians tend to be more resistant to beta-adrenergic stimulation. Although energy expenditure and SNS activity were not directly related, a higher SNS tone may either promote or reflect elevated levels of spontaneous physical activity and therefore influence both energy balance and body composition. PMID- 8510517 TI - Lack of clinical evidence of sodium retention in children with idiopathic short stature treated with recombinant growth hormone. AB - In adults patients, administration of human growth hormone and growth hormone synthesized by recombinant DNA technology (rGH) results in sodium and fluid retention and weight gain. This study was performed to determine whether rGH administration in children with idiopathic short stature (ISS) caused any clinical evidence of sodium retention. The parameters assessed included blood pressure, height, weight, plasma renin activity (PRA), aldosterone, and atrial natriuretic peptide (ANP). These were measured in nine treated children after 0, 3, 6, 9, and 12 months of growth hormone therapy; seven untreated children served as controls. After 12 months, the treated children had no significant increases in measurements of blood pressure, PRA, aldosterone, and ANP. Although treated children gained more weight than control patients, they also grew faster. Therefore, there was no significant difference in weight for height percentile for treated children when compared with normal controls. After 1 year of therapy, the administration of rGH to children with ISS does not result in any clinically significant evidence of sodium retention. PMID- 8510518 TI - The association of obesity and glucose and insulin concentrations with bone density in premenopausal and postmenopausal women. AB - Obese subjects have increased bone density relative to non-obese subjects, yet this relationship is not fully understood. We examined whether alterations in glucose or insulin concentrations might explain the effect of obesity on bone density in 317 women from the San Antonio Heart Study, a population-based study of diabetes. We measured fasting and 2-hour plasma glucose and fasting and 2-hour serum insulin levels. Bone density was assessed by a Hologic dual-photon absorptiometer. Lumbar spine and femoral neck density were positively correlated with body mass index (BMI). Femoral neck density also was positively correlated with fasting insulin level in younger women after adjustment for age (r = .214, P < .01). After further adjustment for BMI, femoral neck density was not significantly correlated with fasting insulin level (P = .08). The magnitude of the estimated femoral neck density difference for a 32.2-microU/mL decrease in fasting insulin level (the difference in insulin concentrations between nondiabetics and diabetics) was 0.13 g/cm2. Adjustment for glucose and insulin concentrations does not explain the association between bone density and obesity. PMID- 8510519 TI - Regulation of adenylate cyclase in plasma membranes of human intraabdominal and abdominal subcutaneous adipocytes. AB - Fat cells were isolated from human subcutaneous, omental, and mesenteric adipose tissue. Omental fat cells were the smallest (438 pL), subcutaneous cells were intermediate (494 pL), and mesenteric cells were the largest (600 pL). There was no difference in the stimulation of adenylate cyclase by isoproterenol in plasma membranes of adipocytes prepared from the three sites. N6 (phenylisopropyl)adenosine inhibited 7-deacetyl-6-(N-acetylglycyl)forskolin stimulated adenylate cyclase activity more potently in subcutaneous than in intraabdominal (especially omental) fat cell membranes. Kd values of the adenosine A1 receptors for 1,3-[3H]dipropyl-8-cyclopentylxanthine were similar in the three fat depots, but the receptor number as calculated per milligram protein was lower in omental than in abdominal subcutaneous adipocytes. Differences in adipocyte size cannot explain regional differences in the regulation of adenylate cyclase. PMID- 8510520 TI - Glycerol kinetics with parenteral lipid emulsions (long-chain triglycerides, medium-chain triglycerides, and structured lipids) in rats. AB - Several studies have reported that parenteral lipid emulsions containing medium chain triglycerides (MCT) and structured lipids (SL) are better utilized than those containing long-chain triglycerides (LCT). The objective of this study was to test the hypothesis that parenteral LCT require more extensive modification via hydrolysis and reesterification (triglyceride-free fatty acid [TG-FFA] recycling) for effective utilization, whereas MCT and SL do not. As an index of TG-FFA cycling activity, we measured glycerol and palmitate kinetics in rats (204 to 243 g) fed parenterally one of three isocaloric (250 kcal/kg/d) isonitrogenous (1.5 g N/kg/d) diets with half of the nonprotein energy from glucose and the rest from either LCT, LCT plus MCT, or SL for 5 days. Two experiments were performed. On day 5, rats were given a 7-to 8-hour infusion of either 5H2 Glycerol and 1-14C Palmitate bound to albumin to measure palmitate and glycerol kinetics (experiment 1), or U-13C glucose to determine the proportion of endogenous glycerol production derived from glucose (experiment 2). Data are presented as means +/- SEM. Endogenous glycerol production was significantly higher with LCT (11.33 +/- 2.89 mmol/kg/h) than with SL (2.91 +/- 0.62 mmol/kg/h). The value for the physical mixture of LCT plus MCT (5.46 +/- 1.29 mmol/kg/h) fell midway between that for LCT and SL (P = NS). There were no significant differences in palmitate kinetics or oxidation. The increased glycerol production is due to the mobilization of endogenous triglyceride and is consistent with a higher rate of TG-FFA cycling being involved in the metabolism of LCT than of SL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510521 TI - Lipoprotein(a) plasma concentrations associated with lipolytic activities in eight kindreds with familial combined hyperlipidemia and normolipidemic subjects. AB - The relationship between lipoprotein(a) [Lp(a)] and metabolism of triglyceride rich lipoproteins (TRL) was studied in 58 untreated patients with familial combined hyperlipidemia (FCH) from eight different kindreds, 17 spouse controls, and 17 unrelated controls. Lp(a) plasma concentrations were not significantly different between FCH subjects (343 +/- 61 mg/L, mean +/- SEM) and controls (249 +/- 52 mg/L). In FCH, log-transformed Lp(a) levels correlated positively with postheparin lipoprotein lipase ([LPL] r = .61, P = .0002) and hepatic lipase ([HL] r = .46, P = .008) activities and total plasma cholesterol level (r = .30, P = .03). In controls, Lp(a) correlated with LPL (r = .50, P = .04) and total plasma cholesterol level (r = .51, P = .003). In eight FCH patients, treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin resulted in significantly increased mean LPL activities and plasma Lp(a) concentrations. In three of these FCH patients, repeated measurements during 1 year demonstrated that changes in Lp(a) concentrations were paralleled by similar changes in LPL activity, but not HL activity. The observed correlation between postheparin plasma lipolytic activities and Lp(a) plasma concentrations suggests a connection between the metabolism of TRL and Lp(a). PMID- 8510523 TI - Chronic malnutrition impairs insulin sensitivity through both receptor and postreceptor defects in rats with mild streptozocin diabetes. AB - The effect of coexisting chronic malnutrition on insulin sensitivity in mild diabetes was studied in rats. Food intake was restricted over an 8-week period to 50% of ad libitum intake by pair-feeding 4-week-old littermate rats injected with streptozocin ([STZ] 40 mg/kg intraperitoneally) at 8 weeks. Significantly greater glucose intolerance and hypoinsulinemia were seen in response to a glucose load in the malnourished diabetic group (P < .00005), suggesting that chronic malnutrition significantly accentuated beta-cell dysfunction from STZ. Significantly greater insulin resistance was also seen, with the percentage rate constant for glucose disappearance after a bolus of insulin being markedly impaired (P < .0001) in the malnourished diabetic group (1.5% +/- 0.2% x min-1 [SE]) compared with ad libitum-fed diabetic and normal rats (3.6% +/- 0.6% x min 1 and 4.7% +/- 0.7% x min-1, respectively; P < .01). Insulin binding to receptor in liver plasma membranes was altered by malnutrition (P < .00005), with the affinity of binding being significantly reduced compared with that of ad libitum fed diabetic controls (P < .0001) at both the high-affinity site (3.9 +/- 0.2 v 13.7 +/- 3.3 x 10(-7) x mol/L-1) and low-affinity site (2.7 +/- 0.4 v 20.1 +/- 3.8 x 10(-5) x mol/L-1). During a constant glucose and insulin infusion (1.67 mU/kg/min), glucose clearance was significantly lower in malnourished rats (5.3 +/- 0.7 v 8.6 +/- 1.7 mL/gk/min, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510522 TI - Gamma-aminobutyric acid mediation of the inhibitory effect of endogenous opioids on the arginine vasopressin and oxytocin responses to nicotine from cigarette smoking. AB - Previous studies have demonstrated that naloxone exerts positive effects on the responsiveness of arginine vasopressin (AVP) and oxytocin (OT) to nicotine, suggesting inhibitory actions of endogenous opioids. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in the regulation of naloxone-sensitive endogenous opioid action. AVP and OT secretory patterns after (two nonfilter) cigarette smoking were examined in seven normal male subjects with (experimental test) and without (control test) concomitant treatment with naloxone (4 mg in an intravenous bolus plus 6 mg infused over 2 hours), the GABAergic agent sodium valproate (600 mg in three divided doses orally), or the combination of naloxone and sodium valproate. Cigarette smoking increased by 2.4-fold (peak v baseline) the plasma concentrations of AVP without modifying OT levels. In the presence of naloxone, plasma AVP and OT levels in response to nicotine were significantly higher than those in the control test. In the naloxone plus nicotine test, AVP levels increased 4.2-fold (peak v baseline) and OT concentrations increased 1.6-fold (peak v baseline). Pretreatment with sodium valproate changed neither AVP nor OT secretory patterns during the cigarette-smoking test. In contrast, sodium valproate abolished the facilitating effect of naloxone on both AVP and OT responses to nicotine. In the sodium valproate plus naloxone plus nicotine test, plasma AVP and OT levels were not significantly higher than those obtained during the nicotine test. These data indicate a GABAergic mediation of the inhibitory modulation by endogenous opioids of the AVP and OT responses to nicotine. PMID- 8510524 TI - Carbohydrate fermentation decreases hepatic glucose output in healthy subjects. AB - Fermentation of undigested carbohydrate produces short-chain fatty acids (SCFA), some of which have been shown to reduce hepatic glucose production (HGP) in animals. The aim of this study was to examine whether carbohydrate fermentation decreases HGP in man. Ten healthy subjects consumed 90-g carbohydrate portions of either brown rice or barley for dinner in random order 1 week apart. The following morning, glucose kinetics were measured basally and during an oral glucose tolerance test (OGTT). HGP was calculated as the difference between the total rate of glucose appearance (calculated from % enrichment of 6,6 dideuterated glucose [6,6 D2 glucose]) and the rate of appearance of gut-derived glucose (calculated from 6-3H glucose in the glucose drink). To detect fermentation, breath H2 content was measured by end-expiratory sampling of alveolar air. Significantly more breath H2 was produced after barley consumption (24 +/- 4 v 4 +/- 1 ppm, P < .001), indicating that barley contains more fermentable carbohydrate than rice. Glucose tolerance improved after the barley meal, with the peak OGTT plasma glucose concentration being 0.7 mmol/L lower than that after the rice meal (7.7 +/- 0.4 v 8.4 +/- 0.3 mmol/L, P < .05). This was primarily due to a 30% reduction in HGP (area under the curve, 909 +/- 116 v 1,295 +/- 157 mumol/kg; P < .01). No difference in the rates of glucose disappearance or gut glucose absorption was observed. However, serum free fatty acid (FFA) concentrations were significantly reduced the morning after the barley meal. In summary, carbohydrate fermentation enhances the suppression of HGP and FFA levels by oral glucose in man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510525 TI - Evidence that suppression of insulin secretion by insulin itself is neurally mediated. AB - We examined the mechanism by which an increase in blood insulin concentration inhibits insulin secretion by the pancreas. To this end, we determined plasma C peptide concentrations during euglycemic-hyperinsulinemic (approximately 500 pmol/L) clamps in five patients with insulin-dependent diabetes mellitus (IDDM) after combined pancreas and kidney (P/K) transplantation, in five nondiabetic patients after kidney transplantation (K), and in six normal control subjects. Hyperinsulinemia decreased C-peptide concentrations in K patients (by 60%, P < .01) and controls (by 35%, P < .05), but not in P/K patients (653 +/- 115 v 702 +/- 197 pmol/L before and after 4 hours of hyperinsulinemia, respectively). The main difference between K patients and controls and P/K patients was that the pancreas in K patients and controls was innervated, whereas the transplanted pancreas of K/P patients was denervated. The data therefore suggested that the inhibition of pancreatic insulin secretion by hyperinsulinemia was neurally mediated. PMID- 8510527 TI - Recombinant DNA. Part I. PMID- 8510526 TI - Serum growth hormone response to growth hormone-releasing hormone in non-obese and obese adults with hypopituitarism. AB - The clinical consequences of growth hormone (GH) deficiency (GHD) in adults have not been defined. Standard methods of measuring GH reserve in children may not be reliable in adults. In addition, obesity in normal adults diminishes GH responsiveness to provocative stimuli; this inhibition of GH release is reversed with pyridostigmine (PD). We investigated the use of GH-releasing hormone (GHRH) as a method to assess pituitary GH secretory reserve (as defined by peak GH response to GHRH) in both non-obese and obese (ie, > 115% ideal body mass index [BMI]) adults with hypothalamic-pituitary tumors. Nine non-obese patients (NOP) and 10 obese patients (OP) were studied with 11 non-obese controls (NOC) and 10 obese controls (OC). All study groups received GHRH (1 microgram/kg intravenous bolus) with blood sampling at -15, 0, 15, 30, 45, 60, 75, and 90 minutes. OC and OP received 120 mg PD orally 1 hour before GHRH injection. Mean serum GH responses in NOC and OC were significantly higher (P < .05) than those in NOP and OP, respectively, 15 minutes after GHRH injection, and remained so throughout the time-course of the test. Mean +/- standard error of the mean (SEM) peak GH level (microgram/L) was lower in NOP than in NOC (5.1 +/- 1.6 v 21.2 +/- 4.4, P < .01) and lower in OP than in OC (4.6 +/- 1.8 v 15.5 +/- 2.2, P < .01). Mean +/- SEM peak GH level was also lower in NOP than in OC (5.1 +/- 1.6 v 15.5 +/- 2.2 micrograms/L, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510528 TI - Automated fluorescent DNA sequencing of polymerase chain reaction products. AB - The methods described in this chapter provide some useful approaches for DNA sequencing of templates produced by PCR. These procedures have been employed successfully for large-scale DNA sequencing of cosmid fragments subcloned in plasmid or M13 vectors, and for sequence analysis of cDNAs cloned in bacteriophage lambda vectors. In addition, the method describing direct sequencing from PEG-precipitated PCR product has been used successfully for analysis of Caenorhabditis elegans genomic and cDNA sequences. It is important to reiterate that for every combination of amplification primer pair and target DNA, there is an optimal method for PCR amplification; the ability to sequence the products of any PCR experiment directly will also vary. A coupled PCR/DNA sequencing method that works well for one experimental system may work quite poorly with others. Hence, a few days or hours spent optimizing PCR amplification conditions and selecting the best DNA sequencing method for the target DNA of interest will be time well spent. PMID- 8510530 TI - High-speed DNA sequencing by capillary gel electrophoresis. PMID- 8510529 TI - Specific primer-directed DNA sequence analysis using automated fluorescence detection and labeled primers. PMID- 8510531 TI - Producing single-stranded DNA in polymerase chain reaction for direct genomic sequencing. PMID- 8510532 TI - Preparation and fluorescent sequencing of M13 clones: microtiter methods. PMID- 8510533 TI - DNA sequencing with direct transfer electrophoresis and nonradioactive detection. PMID- 8510534 TI - Adenine-specific DNA chemical sequencing reaction. PMID- 8510535 TI - Direct DNA sequencing of polymerase chain reaction-amplified genomic DNA by Maxam Gilbert method. PMID- 8510536 TI - Direct sequencing of lambda gt11 clones. PMID- 8510537 TI - Sequencing products of polymerase chain reaction. PMID- 8510538 TI - Sequencing of in vitro amplified DNA. PMID- 8510539 TI - Amplification of bacteriophage library inserts using polymerase chain reaction. PMID- 8510540 TI - Genetic analysis using polymerase chain reaction-amplified DNA and immobilized oligonucleotide probes: reverse dot-blot typing. AB - The reverse dot-blot method is a simple and rapid diagnostic procedure that allows screening of sample for a variety of mutations/polymorphisms in a single hybridization reaction. Several methods of immobilizing the oligonucleotide probes are discussed. The reverse dot-blot method has several unique properties that are valuable in a diagnostic setting: (1) the typing results from a single sample can be located on a single strip. This facilitates scanning and interpretation of the probe reactivity patterns and minimizes the potential for user error. (2) The test can utilize premade typing strips. This minimizes user labor as well as error potential and allows the use of standardized reagents. (3) Unlike dot-blot/oligonucleotide typing, only the PCR product is labeled, eliminating the potential problem of probes labeled to different specific activities. This method has already been used in the areas of forensic genetic typing (the HLA-DQ alpha Amplitype test), tissue typing for transplantation (the HLA-DR beta) test, cystic fibrosis screening, as well as in a variety of research applications. PMID- 8510541 TI - Polymerase chain reaction amplification of specific alleles: a general method of detection of mutations, polymorphisms, and haplotypes. PMID- 8510542 TI - Chromosome assignment by polymerase chain reaction techniques. PMID- 8510543 TI - Cross-species polymerase chain reaction: cloning of TATA box-binding proteins. PMID- 8510544 TI - Magnetic DNA affinity purification of yeast transcription factor. PMID- 8510545 TI - Affinity selection of polymerase chain reaction products by DNA-binding proteins. PMID- 8510546 TI - Protein-blotting procedures to evaluate interactions of steroid receptors with DNA. PMID- 8510547 TI - Specific recognition site probes for isolating genes encoding DNA-binding proteins. PMID- 8510548 TI - Unidirectional deletion mutagenesis for DNA sequencing and protein engineering. PMID- 8510549 TI - In situ detection of DNA-metabolizing enzymes following polyacrylamide gel electrophoresis. AB - We have presented several protocols for producing an in situ activity gel that allows detection of various DNA-metabolizing enzymes. Both nondenaturing polyacrylamide and SDS-polyacrylamide activity gel electrophoresis procedures were detailed. Combining the use of defined [32P]DNA substrates with product analysis, these procedures detected a wide spectrum of enzymatic activities. The ability to detect 7 different catalytic activities of 15 different enzymes provides encouragement for expanded applications. It is hoped that others will find this technique applicable for detecting these enzymes and other activities in different biological systems. The modification of DNA in situ and the creation of intermediate substrates within activity gels should prove extremely useful for dissecting the enzymatic steps of DNA replication, repair, recombination, and restriction, as well as the metabolic pathways of other nucleic acids. PMID- 8510550 TI - Preparation and storage of competent Escherichia coli cells. PMID- 8510551 TI - Storage of unamplified phage libraries on nylon filters. PMID- 8510552 TI - Tissue-print hybridization on membrane for localization of mRNA in plant tissue. PMID- 8510553 TI - Localization of cell wall proteins using tissue-print western blot techniques. PMID- 8510554 TI - Tissue-print hybridization for detecting RNA directly. PMID- 8510555 TI - Recovery and cloning of genomic DNA fragments from dried agarose gels. PMID- 8510556 TI - Genetic analysis using random amplified polymorphic DNA markers. PMID- 8510557 TI - Direct sequencing of polymerase chain reaction products from low melting temperature agarose. PMID- 8510558 TI - Fluorescent and radioactive solid-phase dideoxy sequencing of polymerase chain reaction products in microtiter plates. PMID- 8510559 TI - Properties of a phosphatidylcholine derivative of diphenyl hexatriene (DPH-PC) in lymphocyte membranes. A comparison with DPH and the cationic derivative TMA-DPH using static and dynamic fluorescence. AB - Using static and dynamic fluorescence we studied the fluorescence properties of a phosphatidylcholine analog of 1,6-diphenyl-1,3,5-hexatriene (DPH-PC) incorporated in lymphocyte plasma membranes with respect to DPH and its cationic derivative 1 (4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), in order to study if phospholipid derivatives of DPH may be used to investigate structural and physicochemical properties of specific membrane lipid domains. DPH-PC and TMA DPH showed similar fluorescence polarization values that were significantly higher with respect to DPH, suggesting a localization of the fluorescent portion of DPH-PC in a more ordered region of the membrane which was probably due to the elecrostatic interactions between phospholipid head-groups. The localization of the fluorescent moiety of DPH-PC near the membrane surface was also supported by the study of the fluorescence decay of the three probes using frequency-domain fluorometry. The main lifetime component of DPH-PC was rather similar to that of TMA-DPH (6.74 versus 6.24, ns) but considerably lower with respect to DPH (10.52 ns), in agreement with data obtained from exponential analysis. In lymphocyte membranes obtained from concanavalin A treated cells, a significant decrease of fluorescence polarization has been shown with DPH and its phosphatidylcholine derivative, but not with TMA-DPH. In liposomes obtained from total lipids extracted from lymphocyte membranes, a decrease of fluorescence polarization has been observed only with DPH. Our results suggest that DPH-PC localizes the fluorescent portion of its molecule in membrane microenvironments of different properties with respect to those probed by DPH and TMA-DPH. The use of DPH phospholipid derivatives and other DPH-probes may represent an useful tool to study plasma membrane heterogeneity in biological membranes. PMID- 8510560 TI - Involvement of a pertussis toxin-sensitive G protein-coupled phospholipase A2 in agonist-stimulated arachidonic acid release in membranes isolated from bovine iris sphincter smooth muscle. AB - We have shown that in bovine iris sphincter membranes G proteins are involved in coupling muscarinic-, PGF2 alpha-, endothelin- and platelet-activating factor receptors to the activation of phospholipase A2 and the release of arachidonic acid. GTP gamma S and GTP gamma S plus carbachol stimulated arachidonic acid release in the membranes in a dose- and time-dependent manner. Nucleotide stimulation was specific to GTP gamma S, since GDP, GDP beta S and ATP had no effect. The stimulatory effect of GTP gamma S plus carbachol was blocked by atropine and it required the presence of physiological concentrations of Ca2-. AIF4-, which bypasses the receptor and directly activates the G protein, induced arachidonic acid liberation in the intact iris sphincter, but was ineffective in the membranes. Addition of GTP gamma S plus carbachol to sphincter muscle membranes prelabeled with [3H]inositol or 3H-arachidonic acid resulted in the formation of lysophosphatidylinositol and the liberation of arachidonic acid, thus suggesting the involvement of phospholipase A2. In vitro treatment of the iris membranes with pertussis toxic inhibited arachidonic acid release by the agonists. This is in contrast to the pertussis toxin-insensitive G protein that activates phospholipase C in this tissue (22). These data demonstrate that in the iris sphincter a G protein is involved in the step between receptor activation and the activation of phospholipase A2, and that arachidonic acid release in this tissue is mediated by a pertussis-toxin-sensitive G protein-coupled phospholipase A2. Thus, GTP can regulate arachidonic acid release and its subsequent conversion into eicosanoids by stimulating its formation. PMID- 8510561 TI - Role of target membrane structure in fusion with influenza virus: effect of modulating erythrocyte transbilayer phospholipid distribution. AB - To study the role of the target membrane in influenza virus fusion we chose erythrocyte membranes whose phospholipid arrangement can readily be modified. The phospholipids of normal erythrocytes are arranged asymmetrically across the plasma membrane; phosphatidylcholine (PC) and sphingomyelin are predominantly on the outer surface, whereas others such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are predominantly restricted to the inner leaflet. However, erythrocytes can be lyzed and resealed under conditions where the asymmetric distribution of phospholipids is lost or retained. Low pH-induced fusion of the A/PR 8 strain of influenza virus, monitored spectrofluorometrically by the octadecylrhodamine dequenching assay, was more rapid with lipid-symmetric erythrocyte ghosts than with lipid-asymmetric ghosts or intact erythrocytes. Neither conversion of PS in the lipid-symmetric ghost membrane to PE by means of the enzyme PS decarboxylaze, nor incorporation of spin-labeled phospholipid analogs with PS, PC or PE headgroups into the outer leaflet of lipid-asymmetric erythrocytes altered rates or extents of fusion of A/PR 8 with the modified target. These results indicate that effects on influenza virus fusion are not associated with any particular phospholipid headgroup, but rather related to the packing characteristics of the target membrane. PMID- 8510562 TI - Synthesis of N-(4'-pyridoxyl)sphingosine and its uptake and metabolism by isolated cells. AB - N-(4'-pyridoxyl)sphingosine was synthesized and characterized as a stable compound for specialized delivery of a bioactive lipid. It was found to be facilely taken up by hepatocytes although by a mechanism more typical for lipids than the one used by natural vitamin B6. Some of the N-(4'-pyridoxyl)sphingosine was metabolically acted upon inside the cell to release pyridoxal 5'-phosphate and sphingosine, but formation of pyridoxal 5'-phosphate from the synthetic compound was poor compared with natural vitamin forms of B6, which may partly be due to entrapment within cell membranes and to constraints at the level of cytosolic pyridoxal kinase which is responsible for phosphorylation of the vitamin. Unlike the parent long-chain base, the B6 conjugate was not particularly cytotoxic. Furthermore, the compound was neither an activator nor inhibitor of the respiratory burst of human neutrophils. These findings identify N-(4' pyridoxyl)sphingosine as an interesting tool for studies of the cellular transport, metabolism, and functions of both vitamin B6 and sphingosine. PMID- 8510563 TI - Isolation of lactose permease mutants which recognize arabinose. AB - In the present study lactose permease mutants were isolated which recognize the monosaccharide, L-arabinose. Although the wild-type permease exhibits a poor recognition for L-arabinose, seven independent mutants were identified by their ability to grow on L-arabinose minimal plates. When subjected to DNA sequencing, it was found that all seven of these mutants were single-site mutations in which alanine 177 was changed to valine. The wild type and valine 177 mutant were then analyzed with regard to their abilities to recognize and transport monosaccharides and disaccharides. Free L-arabinose was shown to competitively inhibit [14C]-lactose transport yielding a Ki value of 121 mM for the Val177 mutant and a much higher value of 320 mM for the wild-type. Among several monosaccharides, D-glucose as well as L-arabinose inhibited lactose transport in the Val177 mutant to a significantly greater extent, while D-arabinose and D xylose only caused a slight inhibition. On the other hand, kinetic studies with sugars which are normally recognized by the wild-type permease such as [14C] galactose and [14C]-lactose revealed that the Val177 mutant and wild-type strains had similar transport characteristics for these two sugars. Overall, these results are consistent with the notion that the Val177 substitution causes an enhanced recognition for particular sugars (i.e. L-arabinose) but does not universally affect the recognition and unidirectional transport for all sugars. This idea is further supported by the observation that site-directed mutants containing isoleucine, leucine, phenylalanine, or proline at position 177 also were found to possess an enhanced recognition for L-arabinose. PMID- 8510564 TI - Human immunodeficiency virus type 1 (HIV-1) tat-protein stimulates the production of interleukin-6 (IL-6) by peripheral blood monocytes. AB - In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV 1) recombinant tat-protein on the production of interleukin-6 (IL-6), granulocyte/macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) by purified peripheral blood monocytes. Whereas no effects were observed on TNF-alpha and GM-CSF production, recombinant tat-protein was able to induce the production of IL-6 by peripheral blood monocytes in a dose dependent fashion for concentrations ranging from 1 ng/ml to 1 micrograms/ml. Pre exposure of tat-protein with a polyclonal neutralizing anti-tat antibody (dilution 1:100) completely abrogated the tat-dependent increase in IL-6 production. The ability of tat-protein to selectively stimulate the production of IL-6 by peripheral blood monocytes could help to explain the presence of elevated levels of IL-6 in the serum of HIV-1 seropositive individuals, especially in patients in advanced stages of the disease with an active viral replication. PMID- 8510565 TI - A simple method to detect HIV-1 protein specificity of IgG intrathecal synthesis in HIV-1 infection. AB - There is currently no simple method to detect the antigen specificity of anti-HIV 1 IgG intrathecal synthesis (IS). Fifty-seven pairs of serum and corresponding CSF from 29 HIV-1 seropositive patients were adjusted to an identical concentration of total IgG and tested by a commercial HIV-1 Western Blot (WB) assay. IgG IS to a given HIV-1 protein was demonstrated when the corresponding band was present in CSF but absent or significantly less represented in serum. A total anti-HIV-1 IS was defined as the presence of an IS to one or more HIV-1 antigens. Our WB analysis of CSF and serum, compared with conventional mathematical formulas, showed a higher sensitivity in demonstrating anti-HIV-1 IgG IS. Moreover, the method disclosed which HIV-1 proteins represent the target of IgG IS. This procedure is easy to perform and therefore may represent a valuable tool to study central nervous system (CNS) involvement by HIV-1 during different stages of infection. PMID- 8510566 TI - Booster PCR: evaluation of an improved method for amplification of a few HIV-1 proviral DNA sequences. AB - A biphasic polymerase chain reaction designed as booster PCR for the detection of human immunodeficiency virus type-1 (HIV-1) was evaluated in samples containing a very low number of target DNA. We examined DNA samples obtained from chronically infected H9/HTLV-III B cells and purified plasmidic DNA containing the entire HIV 1 genome. By using booster PCR we detected HIV-1 DNA sequences up to 5 infected cells in samples containing about 2 micrograms of genomic DNA, and up to 1 copy of plasmidic DNA in samples containing about 0.5 microgram of genomic DNA. Otherwise by using standard PCR HIV-DNA up 100 infected cells and up to 20 copies from plasmidic DNA could be detected. Our experiments in amplification of HIV-1 proviral DNA have demonstrated that booster PCR enhances sensitivity of detection of standard PCR in small quantities of target sequences at least 20-fold with no loss of specificity. PMID- 8510567 TI - The reshaping process of Klebsiella pneumoniae cells after removal of mecillinam, an antibiotic that causes transition from rod to coccal shape. AB - The process of bacterial morphogenesis that leads to rod shape formation was studied in synchronous cells during the reshaping process after removal of mecillinam, a beta-lactam antibiotic which, by specifically inhibiting lateral wall formation of rods, cause rod-to-sphere transition in Gram-negative rods. The addition of mecillinam for 50 min of the cell cycle made the cells to skip a division, while the addition of the antibiotic for 30 min (or less), allowed the cells to divide regularly. In order to study the interplay between lateral wall elongation and septum formation in reacquisition of rod shape, we evaluated the effect of re-adding mecillinam or adding piperacillin, a specific inhibitor of septum formation, at various stages of the reshaping process. It was found that mecillinam was active only when added within the first 30 min of the reshaping process, while piperacillin was active only after 30 min when the cells were close to starting to divide again. These findings provide further support for our previous proposal that, in bacterial rods, elongation and septation are two alternating and competing events of the cell cycle, and are linked to each other in such a way as to force bacterial rods to grow to a given length. PMID- 8510568 TI - Activation of the complement system by Francisella tularensis lipopolysaccharide. AB - We have shown by combining lipopolysaccharide (LPS) extracted and purified from Francisella tularensis live vaccine strain (LVS) with normal complement and back titrating with sensitised sheep red blood cells that the LPS activates complement. Deionising the LPS and converting it into the single salt forms of pyridine, ethanolamine and triethylamine altered the ability to activate complement according to the apparent molecular weight due to aggregation. Francisella tularensis LPS activated complement deficient in a component of the alternative pathway (factor B) but failed to activate complement deficient in a component of the classical pathway (C1q). In addition normal complement suspended in ethyleneglycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) which inactivates the classic pathway was not activated by LPS, and we concluded that the LPS activates complement predominantly via the classical pathway. LPS bound to specific monoclonal antibodies activated complement more than LPS alone. An anti-core monoclonal antibody was approximately tenfold more potent when bound to LPS then an anti-O side chain monoclonal antibody in activating complement. PMID- 8510569 TI - Rapid access to pharmacokinetics data and correlation between antimicrobial susceptibility results and drug tissue distribution using a personal computer. AB - MYMIC is a computer-aided system capable of integrating antibiotic susceptibility data with the concentrations the drugs reach in various body tissues and fluids by calculating site concentration/minimal inhibitory concentration quotients. The program can be run on any low-cost personal computer operating under MS-DOS, provided it is equipped with a hard-disk drive and with a minimum of 512 kilobytes of random access memory. The use of the program does not require any knowledge of computer languages. The antibiotic susceptibility data can be entered either as minimal inhibitory concentrations or as inhibitory zone diameters; in the latter case, minimal inhibitory concentrations are automatically calculated via regression formulas. The concentrations obtained by 90 antibiotics in 51 different human tissues and fluids are recorded in a data base of over 1,000 records, obtained from roughly 700 original papers. A MYMIC sample session was simulated by mimicking infections of three different body districts (namely bone, prostate, and sputum) caused by Pseudomonas aeruginosa, Escherichia coli or Providencia stuartii. PMID- 8510570 TI - Peptidoglycan synthesis and its fine chemical composition in dividing and not dividing Klebsiella pneumoniae cocci. AB - Peptidoglycan synthesis and its fine chemical composition were studied in dividing and in non-dividing Klebsiella pneumoniae cocci and compared with rods. The beta-lactam mecillinam, a specific inhibitor of lateral wall elongation which causes rod-to-sphere transition in rods, showed 50% inhibition of the peptidoglycan in normal rods of the parent Mir A12 only if added at an early stage of the cell cycle and no effect if added later or during septation. In the rods of the mutant Mir M7, mecillinam was shown to inhibit 50% of peptidoglycan synthesis until rods become cocci, and thereafter to be absolutely devoid of effects. On the contrary, piperacillin, a specific inhibitor of septum formation, was active on all strains regardless of their cell shape, only if added at 20 and removed at 40 min of the cell cycle. As regards the analysis of peptidoglycan fine chemical composition, bacteria dividing as cocci showed alterations in the muropeptide composition consisting in a 50-fold increase in the tetramer family. This alteration was not seen in the cocci that did not divide as such. These results confirm our previous claim that septum formation and lateral wall elongation are mutually exclusive in normal rods and that septum formation requires the synthesis of a peptidoglycan of different chemical composition. PMID- 8510571 TI - Antimicrobial compounds from Lactobacillus casei and Lactobacillus helveticus. AB - Three strains of Lactobacillus casei and one of Lactobacillus helveticus were examined for antagonistic activity toward twenty five indicator strains of different species. Under conditions eliminating the effects of organic acid and hydrogen peroxide, culture supernatants of all the Lactobacillus strains exhibited a wide spectrum of inhibitory activity toward microorganisms of different genera. The inhibitory compound secreted by one strain of L. casei was active against Clostridium tyrobutyricum. The active components were insensitive to proteolytic enzyme and heat treatment. PMID- 8510572 TI - Isolation and partial characterization of three rumen Lactobacillus plantarum bacteriophages. AB - The first isolation of Lactobacillus plantarum bacteriophages from ruminal fluid is reported. Three bacteriophages were characterized on the basis of plaque morphology, host ranges, stability, electron microscopic morphology and DNA restriction endonuclease digestion patterns. They formed clear plaques and are placed in group A of Bradley's scheme and have identical host ranges. Bacteriophages were stable to urea and chloroform. They were relatively thermostable but partially inactivated by rumen fluid and by acetate. DNA restriction analysis showed that phage L20 had different numbers of cleavage sites in comparison with the next two phages. PMID- 8510573 TI - Polymerase chain reaction in the early diagnosis of HIV-1 infection in high risk subjects. AB - We investigated the presence of the HIV-1 infection using the polymerase chain reaction (PCR) test in seronegative sexual partners of HIV-infected subjects and in children born to seropositive mothers. By using PCR assay, no HIV-1 DNA was detected in 32 female partners of HIV positive patients including three pregnant women who were also studied during pregnancy and after delivery. HIV-1 DNA was found in 12 out of 38 children born to seropositive mothers; five of them also had detectable serum HIV-1 p24 Ag levels. On the whole, our data stress the importance of using a very sensitive technique, i.e. PCR, for the early diagnosis of HIV-1 infection. PMID- 8510574 TI - Pseudomonas aeruginosa and cystic fibrosis: intrastrain variability in relation to intensity of immune response and clinical outcome. AB - Over periods exceeding two years, 63 Pseudomonas aeruginosa strains isolated from three children with cystic fibrosis were characterized using a 154 character auxanogram. Numerical analysis was carried out to establish intrastrain variability in relation to intensity of immune response and clinical outcome. For two patients, strains segregated in two distinct phenons. For the last patient, strains did not cluster. The degree of intrastrain variability during the infection was correlated with an increasing number of precipitins and with an unfavorable clinical outcome. This would suggest that strains which have a singular potential for antigenic variability are more likely to promote a host bacteria conflict. PMID- 8510575 TI - Listeria monocytogenes infections: the organism, its pathogenicity and antimicrobial drugs susceptibility. AB - L. monocytogenes can induce serious, life-threatening infections. Multiple clinical manifestations of the disease include neonatal and perinatal listeriosis, infections in adult immunocompromised patients as well as in normal hosts, with the CNS as the more frequent site involved. Many outbreaks are believed to be food-borne in origin, but there can be other means of transmission. The susceptibility of L. monocytogenes to different antimicrobial drugs is reviewed. Many drugs that are highly effective in vitro show only a moderate activity in vivo, due either to their poor ability to enter the phagocytes and destroy the engulfed bacteria, as with the beta-lactams, ampicillin and amoxicillin, or to their bacteriostatic rather than bactericidal activity, as with the fluoroquinolones, or their affinity for a serum glycoprotein, as with the macrolide antibiotics. The bacterial killing appears to be enhanced by some synergistic drug associations, the best therapeutic results being achieved by trimethoprim-cotrimoxazole and ampicillin plus gentamicin. Other more recent antimicrobial drugs and drug combinations are still under clinical evaluation. PMID- 8510577 TI - Giving midwifery care for the deaf in the 1990s. PMID- 8510576 TI - Education aspects of giving midwifery care for the 1990s. PMID- 8510578 TI - Survival and hard work! PMID- 8510579 TI - Mother Earth. American Indian beliefs and practice in childbearing. PMID- 8510580 TI - Health for people. Lessons from a Bangladeshi health care project. PMID- 8510582 TI - Are midwives ready for change? PMID- 8510581 TI - Breaking down the barriers--midwives turn east. AB - Three-and-a-half years ago the barriers to communication between East and West Europe began to break down. Some of the news that first came through, particularly regarding the health care and living conditions of babies and children, was deeply disturbing and appeals were immediately launched for money, food, medical supplies and professional help. Later, equally tragic news was received about the plight of refugees and victims of the war in Bosnia. Midwives and nurses from the UK were among those who have responded by travelling to the worst affected areas and offering their care and support to mothers and children. PMID- 8510583 TI - First impressions of New York. PMID- 8510584 TI - Team midwifery--a guilty secret. PMID- 8510585 TI - Who helps health professionals with breast-feeding? The Mabel Liddiard Memorial Lecture, 1992. PMID- 8510586 TI - Breast-feeding advice and support clinic. PMID- 8510587 TI - HIV-infected health care workers. PMID- 8510588 TI - The RCM--an international success. PMID- 8510590 TI - Support in pregnancy: the wonder of the underwired bra. PMID- 8510589 TI - Society and womanhood: what influences women's method of feeding their babies? PMID- 8510591 TI - Care study: breast-feeding in the SCBU. PMID- 8510592 TI - HIV transmission. PMID- 8510593 TI - HIV transmission. PMID- 8510594 TI - Midwives to get new safety guidelines on the twin dangers of HIV and hepatitis B. PMID- 8510595 TI - [Controversy regarding plasma level]. PMID- 8510596 TI - [Treatment with the artificial kidney]. PMID- 8510597 TI - [Pathogenesis of coronary heart disease and acute coronary events]. PMID- 8510598 TI - [Distilled water for drinking?]. PMID- 8510599 TI - [Drinking water for infant food?]. PMID- 8510600 TI - Physician payment reform: past and future. AB - Medicare's decision to compensate physicians using a fee schedule based on the relative value of their services was an attempt to rationalize fee-for-service payment of physicians. Reformers hoped also to control the costs of care, improve its quality, and protect access to health services among Medicare beneficiaries. A close examination of the system's provisions indicates, however, that the reform does not address many fundamental problems that have plagued physician payment under Medicare in the past. In the cost area, for example, the new fee schedule does not affect such factors as the basic incentives built into fee-for service medicine and the explosion of new medical technologies. The failure of the program to achieve its goals in cost containment and other areas could result in abandonment of fee-for-service compensation of physicians under Medicare. PMID- 8510601 TI - A critical analysis of studies of state drug reimbursement policies: research in need of discipline. AB - Concerns over pharmaceutical costs and appropriateness of medication use have led state Medicaid programs to restrict drug reimbursement. This article critically reviews 20 years of research on cost sharing, drug reimbursement limits, and administrative limitations on access to particular drugs via formularies, category exclusions, or prior authorization requirements; evaluates their methodological rigor; summarizes the state of current knowledge; and proposes future research directions. Drug reimbursement caps and modest cost sharing can reduce the use of both essential and less important drugs in Medicaid populations; severe reimbursement caps may precipitate serious unintended effects. Limitations on access to particular drugs can cause both rational and irrational drug substitution effects; it is unclear whether such limits reduce expenditures either for drugs or for overall health care. PMID- 8510602 TI - Social contingencies, the aged, and public policy. AB - Today's older population is notably different than it was a few decades ago, both in well-being and in diversity, a shift that must be acknowledged in public policy. The U.S. social insurance system overprotects against highly likely, predictable, and nonvolatile events at the expense of more unlikely, potentially catastrophic, and less volatile events. The public sector, therefore, should move toward proportionally emphasizing health-related, functionally impairing events rather than income maintenance; the private sector is better suited to insuring against predictable and nonvolatile old-age events. A contingent event scheme would: (a) encourage the growth of long-term-care insurance; (b) help bridge the gap between those arguing for greater "efficiencies" in social welfare spending and those pressing for new universal benefits; and (c) bring a new perspective to the "generational equity" debate. PMID- 8510603 TI - The relationship between socioeconomic status and health: a review of the literature. AB - Mortality rates in the developed world have fallen sharply during the twentieth century. Individuals of lower socioeconomic status, however, generally have faced higher mortality rates than individuals of higher status. The literature documenting the relationship between socioeconomic status and health is reviewed, including several recent contributions and evidence from other countries. A conceptual framework then draws two distinctions: one contrasting the relative impact of lifestyle habits with the use of health care on health outcomes; and the other seeking to quantify the importance of resources relative to behavioral factors in explaining differential outcomes. The literature to date has been more successful in documenting health inequalities than in explaining why these inequalities persist. PMID- 8510604 TI - Siblings as caregivers for the seriously mentally ill. AB - The majority of seriously mentally ill people are unmarried and cannot obtain support from spouses or children. Help from parents is time limited. In the absence of spouses and parents, siblings are often the closest relations for many seriously mentally ill people, but their potentially supportive role has rarely been examined. This article reports results from a pilot study of 108 siblings with seriously mentally ill brothers and sisters. The findings indicate that siblings had regular contact and positive relationships with their ill sibs. Furthermore, most were willing to increase their current amount of support. Sibling support was greater when both parents were not alive, resulting in the increased importance of siblings over the life course. Policy markers, mental health professionals, and researchers should pay more attention to the question of sibling support. PMID- 8510605 TI - Fetal nicotine exposure alters ontogeny of M1-receptors and their link to G proteins. AB - Prenatal nicotine exposure has been shown to disrupt the development of cholinergic presynaptic tone and behaviors mediated through muscarinic cholinergic receptors. The current study examines nicotine's effects on ontogeny of postsynaptic muscarinic M1-receptors in rat striatum and hippocampus after continuous maternal infusions of 2 mg/kg/day or 6 mg/kg/day from gestational days 4 through 20. Although brain region weights were unaffected by nicotine exposure, significant alterations in receptor development and receptor regulation by G proteins were found. Postnatal development of striatal M1-receptor binding, as identified with [3H]pirenzepine, was significantly impaired with either of the fetal nicotine regimens. Treatment with 2 mg/kg/day also produced alterations in striatal receptor affinity state, characterized by enhanced ability of an agonist (oxotremorine-M) to displace [3H]pirenzepine; raising the dose to 6 mg/kg/day masked the affinity shift by affecting G-protein regulatory mechanisms, such that addition of the GTP analog, GppNHp, produced a larger decrease in agonist affinity. In the hippocampus, no such effects on receptor binding, affinity state, or G-protein regulation were seen with either regimen. These data thus indicate that fetal nicotine exposure, even at doses that do not cause overt signs of maternal/fetal/neonatal toxicity or growth impairment, influences cholinergic receptor development and regulation of cell signaling mediated by G proteins. The selectivity of effects toward M1-receptors in the striatum, a region with a prenatal peak of neuronal mitosis, as compared to hippocampus, where mitosis peaks postnatally, suggests that vulnerability to nicotine involves a critical phase of cell development, rather than being targeted toward receptors of a given subtype. PMID- 8510607 TI - Neonatal exposure to bFGF exerts NGF-like effects on mouse behavioral development. AB - Brain cells are naturally exposed to a variety of trophic factors during development. Basic Fibroblast Growth Factor (bFGF), a protein found in the central nervous system (CNS) enhances both survival and proliferation of several CNS cell lines. Neonatal mice of the CD1 outbred strain were injected intracerebroventricularly (ICV) with bovine bFGF on postnatal days 2, 4, and 7. bFGF, dissolved in 25 microliters of saline, was given in the 1, 5, 25, and 1000 ng doses. Physical traits such as body weight gain, body length, and tail length were recorded from postnatal day (PND) 2 to PND 12. Neurobehavioral development was scored according to a modified Fox's Scale. The ultrasonic vocalization pattern (PND 8), homing performance (PND 10), open-field activity and exploration of a novel object (PND 18) were also assessed. Pups receiving 25 and 1000 ng doses of bFGF showed a slight but significant acceleration in the appearance of some early sensorimotor reflexes, such as weak and tactile stimulation, forelimb placing and grasping, and screen climbing, during the first postnatal weeks. The other responses were less affected or not affected at all. Data are compared with similar systemic exposure of neonatal mice to Nerve Growth Factor (NGF). PMID- 8510606 TI - Developmental neurotoxicity following neonatal exposure to 3,3' iminodipropionitrile in the rat. AB - Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN), induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backward locomotion, and sensory disruption. We report here the behavioral effects of developmental exposure to IDPN in the rat. Animals were exposed (IP) to either saline, 75, 150, or 300 mg/kg/day on postnatal days (PND) 5-7. Animals were tested for: Figure-8 maze activity (PND 13-60); olfactory discrimination learning (PND 18 & 24); T-maze alternation and position discrimination learning (PND 25 & 26); acoustic startle response (PND 23, 61, & 62); passive avoidance (PND 70). To better define the dose response, a separate group of animals was exposed to either saline or 225 mg/kg/day (PND 5-7) and tested in the activity, T-maze, and startle paradigms. Animals exposed to 225 mg/kg/day and 300 mg/kg/day had decreased weight gain and lethality was 25% in the latter group. Signs of the IDPN syndrome, evident in the 225 and 300 mg/kg/day groups, persisted throughout the course of the study. IDPN exposed animals (300 mg/kg/day) were hyperactive on PND 17-60, failing to develop habituation in the Figure-eight maze until PND 60. The acoustic startle response was depressed for the 225 and 300 mg/kg/day groups on PND 23 only. Auditory thresholds were elevated for a high-frequency (40 kHz) but not a low-frequency tone (5 kHz) for the 225 and 300 mg/kg/day groups, indicating a hearing loss. IDPN treatment also disrupted performance of olfactory discrimination learning and produced cognitive deficits in T-maze learning in infants (300 mg/kg/day). That cognitive deficits also appeared in adulthood (PND 70) was demonstrated by learning deficits in a passive avoidance task at 150 and 300 mg/kg/day. IDPN (300 mg/kg/day) also caused a decrease in the wet weight of the whole brain (8%) and the cerebellum (12%) but not the hippocampus. These data demonstrate that short term, neonatal exposure to IDPN in the rat produced persistent alterations in sensory, motor, and cognitive aspects of nervous system function. PMID- 8510608 TI - Effects of perinatal diazepam exposure on the sexually dimorphic rat locus coeruleus. AB - Diazepam (DZ) administration over prenatal, postnatal, and pre plus postnatal periods altered the normal expression of the morphological sex differences of the LC. Males were affected only by the prenatal exposure and the effect of this exposure produced an increase in the volume and neuron number of male's LC. By contrast, females were affected by both pre and postnatal treatments and the effect of this exposure resulted in a decrease in the volume and neuron number of female's LC. However, pre plus postnatal treatment did not affect female's LC. PMID- 8510609 TI - Home cage behavior and lead treatment in rhesus monkeys: a comparison with open field behavior. AB - Nursery-reared rhesus monkeys were treated with no (n = 4) or moderate levels of lead (n = 4) during the first postnatal year. Mean blood lead levels peaked at 55 micrograms/dl at 5 weeks of age, averaged 36 micrograms/dl for the remainder of the first year postpartum, and declined to < or = 5 micrograms/dl for the 4 monkeys by 2.3 years of age. Previously, the lead-treated monkeys exhibited increased environmental exploration and decreased inactivity in a nonhuman primate version of the open field when tested at 4, 5, and 6 years of age (5,6). The current study was designed to assess behavior in the home cage of these monkeys at 6 years of age to determine: (a) whether the increased exploration was specific to the open field, and (b) any lead-related behavioral alterations specific to the home cage. Each monkey was observed twice weekly for 10 weeks and the duration and frequency of 17 behaviors were recorded. Lead treatment did not result in significant alterations in any of the six behaviors which occurred with enough frequency to warrant analysis. As a whole, all monkeys were either inactive or engaged in self-grooming for a large proportion of the test session. Less frequent were behaviors such as locomotion, environmental exploration, and self-directed behaviors. The distribution of behavioral activities in the home cage differed from that in the open field. Potential reasons for the expression of significant lead-related effects in the open field and not in the home cage are discussed as well as the differences in distribution of behavioral activities. PMID- 8510610 TI - Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin. AB - The ability of a neurobehavioral screening battery to differentiate the effects of two pyrethroids, permethrin and cypermethrin, was assessed in this experiment. Although the structures of these pesticides differ only in the alpha-cyano group, the behavioral syndromes associated with the Type I and II pyrethroids are quite different. The tests included a functional observational battery which is a series of subjective and quantitative measures of neurological function and behavior, and an automated measure of motor activity. Our results verified previous reports in the literature describing these different syndromes, i.e., aggressive sparring behavior, fine to whole-body tremor, hyperthermia, and decreased motor activity for the Type I pyrethroid permethrin, and pawing, burrowing, salivation, whole body tremor to choreoathetosis, hypothermia, and lowered motor activity for the Type II pyrethroid cypermethrin. In addition, we report that permethrin produced decreased grip strengths, increased resistance to capture, increased reactivity to a click stimulus, and induced head and forelimb shaking and agitated behaviors, whereas cypermethrin produced pronounced neuromuscular weakness and equilibrium changes, retropulsion, lateral head movements, alterations in responses to various stimuli, and increased urination. Although there were similarities in some effects (e.g., decreased motor activity), the pesticides differed sufficiently in their overall behavioral profiles, and severity and time course of effects, to discriminate these two compounds. Thus, this type of screening approach is sensitive enough to differentiate these pyrethroids for hazard identification purposes. PMID- 8510611 TI - Is use of a cellulose-diluted diet a viable alternative to pair-feeding? AB - Pair-feeding (PF) has been traditionally used as a nutrition control for drugs that reduce food intake during pregnancy. This method of dietary restriction has been shown to induce alterations in the behavior and physiology of the dams, with some consequent effects on their offspring. Dams treated with cocaine typically exhibit a transient reduction in food intake lasting 3-5 days. A novel nutritional control, using a cellulose-diluted diet, was developed to control for this transient anorexia without requiring explicit food restriction. Daily body weights and food and water intake were measured in Sprague-Dawley dams that received subcutaneous injections of 40 mg/kg/3 cc of cocaine hydrochloride (C40) daily on gestational day 8-20, pair-fed (PF) dams that were injected with saline, and nontreated control dams (LC). In addition, another group of dams were placed on a powdered chow diet diluted with cellulose (40% by weight) and were injected with saline from gestational day 8-20 (NC). Both the food intake and body weight gain of NC and PF dams closely matched that of C40 dams. NC dams were more similar in water intake to cocaine-treated dams than PF dams. However, offspring of NC dams exhibited a significant reduction in pup body weight on postnatal day 1 when compared to PF, LC, and C40 offspring, a finding which limits the usefulness of this novel nutritional control procedure. Thus, pair-feeding still appears to be the best available method for controlling the nutritional consequences of developmental toxicants. PMID- 8510612 TI - "Population" characteristics of birthweight in an animal model of alcohol-related developmental effects. AB - A retrospective analysis of a large database of maternal and litter variables in rats collected over several years evaluated the robustness of fetal alcohol effects on birthweight. Pregnant rats were fed a liquid diet in which 35% of the calories were derived from alcohol. Control dams were pairfed an isocaloric liquid diet or were fed lab chow ad lib. Alcohol exposure produced large, highly significant, and reliable decreases in birthweight of male and female pups. Multiple regression analyses indicated that alcohol exposure per se, much more than restricted caloric intake alone, caused these effects. Litters of pairfed dams weighed less than chowfed controls but the effects were less consistent, varying with season and requiring more litters to discriminate the effects of restricted caloric intake. Power analyses indicated that 7 to 12 litters per group are needed for detecting a statistically significant reduction in birthweight due to prenatal alcohol exposure, even with single pups selected at random from each litter. Alcohol-exposed pups also weighed consistently and significantly less than both the chowfed and pairfed pups, whereas differences between chowfed and pairfed groups were much smaller and inconsistent. The results imply that decreased birthweight is a consistent characteristic of prenatal alcohol exposure. PMID- 8510613 TI - [Heredity and environment in the genesis, epigenesis and evolution of the orofacial area]. AB - Genetic and evolutionary aspects of the dento-facial complex are described according to the concept of heredity as a force of preservation for the human species, though ruled by natural selection and by mutational changes. Ontogenesis and growth of the oral structures reflect mutual regulations between genes and environmental factors. Therefore, the authors carry out an analysis of environmental and constitutional factors affecting dental and facial development. Three levels are identified: individual morphogenesis and growth; actual heredity of parietal dento-facial traits; role and meaning of teeth, jaws and temporo mandibular joint during evolution leading to Homo sapiens sapiens. As far as individual development is concerned, genes provide only the input for initial cell proliferation and/or differentiation. Further on, growth and morphogenesis of oro-facial structures takes place by means of cell-to-cell and cell-to substrate interactions. The final, structural result is due to reciprocal interactions among developing structures: muscles modify bone, teeth alignment influences bony bases alignment, ecc. Each structure is genetically determined (teeth, bones, muscles) and each structure carries out epigenetic regulations on other structures: no structure is secluded from biological function of the organism. The inheritance of oro-facial "traits", then, is hardly valuable. First of all, "traits" actually do not exist: they are the product of complex, multifactorial biological mechanisms. Moreover, facial characteristics are affected by polygenic regulation, each gene often showing pleiotropic effects. It has been calculated that 85-90% of facial dimensions in due to epigenetic modifications. Evolution and phylogenesis give evidence about the deep environmental influence on oro-facial morphology. Apart from certain molecular features regarding tooth structure (several dental proteins are today the same as those of the first Vertebrates who lived 500 millions of years ago), tooth number, form, and size depend upon environmental factors. Therefore, dentistry has the important task to preserve fundamental characteristics of dentition, and to intercept environmental pathogenetic factors, as dentition represents a precious instrument for the survival of the human species. PMID- 8510614 TI - [DNA extraction from hard dental tissues]. AB - Two different standard ways of DNA extraction (salting out and phenol-chloroform methods) were assayed in order to recovery nucleic acids from dental tissues. The DNA extracted was tested for purity by means of transverse alternating field electrophoresis (TAFE) using Saccharomyces cerevisiae chromosomes as markers. Both extraction methods give similar qualitative and quantitative results being a DNA yield from hard dental tissues approximately 30% of those extracted from the whole tooth. Our results indicate salting out as a preferable method due to its rapidity and usefulness. PMID- 8510615 TI - [Interleukin-1 beta in the gingival tissues of patients with periodontitis: immunohistochemical data]. AB - Interleukin-1 beta (Il-1 beta) is a cytokine which is considered to play a role in inducing the inflammatory reaction and the bone resorption that takes place in periodontal disease. With the aim of studying the presence and location of Il-1 beta positive cells in this disease, human gingival tissues from 12 patients with periodontitis and from 4 healthy control subjects were examined by immunohistochemical analysis. The cytokine was detected in all the patients having untreated periodontitis, although its content in gingival tissues revealed considerable variations among subjects. Il-1 beta was mainly localized within macrophage-like cells. Il-1 beta positive cells were not present in normal gingival tissue; however in 2 of the subjects considered normal there were few Il 1 beta positive cells in small areas of inflammation present in proximity of the dento-gingival junction. PMID- 8510616 TI - [Arthroscopy of the temporomandibular joint. The instruments and surgical technic]. PMID- 8510617 TI - [The otoneurological and dental picture of Costen's pain-dysfunction syndrome]. AB - The clinical and etiopathogenetic otoneurological aspect of the pain-dysfunction syndrome of the temporomandibular joint is examined in detail. Some possible predictors of positive conventional treatment outcome for this symptomatology are observed. The mainly audiological description of the problem emphasized a frequent but sometimes neglected clinical aspect of such a condition frequently observed in dental practice. PMID- 8510618 TI - [Gingival "thickening" in malformation syndromes. I]. AB - The etiology of generalized gingival enlargement is very heterogeneous. Pregnancy, drugs, systemic diseases, poor oral hygiene, and nutritional impairment can lead to gingival enlargement. This defect can also be presented in several malformation syndromes. Gingival fibromatosis, that may exist as an isolated abnormality or as part of a syndrome, is another condition with gingival enlargement. In this paper, the malformation syndromes with gingival hypertrophy and those with gingival fibromatosis are listed in tables. PMID- 8510619 TI - [Chondrosarcoma of the maxilla. A clinical case report]. AB - Chondrosarcoma are malignant tumour originating in cartilaginous cells which tend to preserve their essentially cartilaginous nature throughout their evolution. They are rare at the level of the maxilla and mandibular. When localized in facial bone, chondrosarcoma follow a more aggressive pattern compared to those localized in long bones. They mainly affect individuals aged between 30 and 60 and show no sexual preference. In the majority of cases, chondrosarcoma have a relatively slow rate of growth. The only valid treatment is radical surgical removal. In overall terms, the prognosis in these patients is not good since the 5-year survival rate is less than 40%. During the period 1980-1992 only 5 cases of chondrosarcoma were diagnosed by the Division of Maxillo-Facial Surgery of the University of Turin. The authors considered it worthwhile to report the last case observed in a premaxillary localization given the advanced age of onset and the typical course of the pathology and treatment received. CASE REPORT. A male 83 year-old patient was referred to use due to a slow growing neoformation in the premaxillary region which had appeared approximately 5-6 months earlier. The patient had previously undergone the avulsion of residual upper teeth due to suspected "toothache". The neoformation filled the premaxilla, deforming the anterior middle portion of the palate and spreading towards the floor of the anterior nasal cavity. The gingiva of the upper alveolar crest presented ulceration with irregular edges and sanious bottom. On palpation the consistency was hard-ligneous and swelling, in continuity with the bone, was slightly painful. Incisional biopsy enabled the diagnosis of chondrosarcoma to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510620 TI - [Primary sarcomas of the maxillofacial area. The clinical assessment of a case of angiosarcoma with a rare location]. AB - Following a short critical review of the most recent literature, the present study reports a case of angiosarcoma of the gingiva, localized at the level of the vestibular surface of the lower incisor region. The intense positive reaction of neoplastic elements to factor VIII-correlated antigen, negative for cytokeratin and positive for vimentin, allowed the vascular nature of the neoplasia to be confirmed. PMID- 8510621 TI - [Gingival hypertrophy in I-cell disease (mucolipidosis II). A report of 2 nonfamilial cases. II]. AB - Two nonconsanguineous patients affected by I-cell disease (mucolipidosis II) are reported. I-cell disease, an oligosaccharidosis, is characterized by severe psychomotor retardation, marked shortness of stature, coarse facies, gingival enlargement, generalized bone demineralization, periosteal cloaking of long bones visible in early infancy, a rapid deteriorating course, and death from heart failure or bronchopneumonia, usually by the age of 5 years. This disorder is the result of a deficiency of glycoprotein N-acetylglucosaminylphosphotransferase activity, necessary for proper intracellular processing of lysosomal enzymes. Inheritance is autosomal recessive. It received the name I-cell disease because of several granular inclusions in the cytoplasm of cultured fibroblasts and amniotic fluid cells observed under phase contrast microscopy. These granules represent altered lysosomes. The two patients, reported here, had a very marked gingival hypertrophy and, for this reason, were referred to the Oral Pathology Service of Galliera Hospital. A gingivectomy was performed on patient 2 to improve the mastication, but few months later gingival hypertrophy reappeared. PMID- 8510622 TI - Nursing care of the neonate receiving prostaglandin E1 therapy. AB - In 1981, the Food and Drug Administration approved prostaglandin E1 (PGE1) for use in the treatment of neonates with congenital heart disease. PGE1 is commonly used in neonatal and pediatric intensive care units to maintain patency of the ductus arteriosus in those cardiac lesions that depend on the ductus for either systemic or pulmonary blood flow. Early recognition of hemodynamic instability and prompt initiation of PGE1 therapy is vital to survival in neonates with ductal-dependent cardiac lesions. Administration of PGE1 allows delay of palliative or corrective surgery until stabilization or transfer of the neonate to a tertiary care facility is achieved. It is also used as a bridge to heart transplantation in neonates in whom this treatment is an option. Congenital anomalies requiring treatment with PGE1 are those that restrict pulmonary blood flow (cyanotic or right-sided outflow tract obstructions) and systemic blood flow (acyanotic or left-sided outflow tract obstructions). Prostaglandin E1 is excreted by the kidneys, and elimination is almost complete within 24 hours after administration; 80 percent of it is rapidly metabolized after one pass through the pulmonary bed. Therefore, a continuous infusion and adequate intravenous access are necessary. Nurses caring for these neonates must have knowledge of all its potential side effects. Some of the most common side effects include cutaneous vasodilation, bradycardia, tachycardia, hypotension, seizure-like activity, hyperthermia, and apnea. PMID- 8510623 TI - Liquid ventilation: a developing technology. AB - Respiratory compromise remains a predominant problem of neonates in intensive care units, producing significant morbidity and mortality. Recent advances in therapy for these infants have focused on diminishing pulmonary inflation pressures. Liquid ventilation, a technique that has been extensively explored in animal models for over 20 years, may have a role in the treatment of pulmonary diseases. This technique utilizes perfluorochemical liquids, which are inert, clear, and odorless, and have a very high solubility for respiratory gases. Liquid ventilation has been studied in numerous animal species under many different conditions. Recent clinical trials have shown the feasibility and potential of this modality in human preterm neonates. This article reviews this technology specifically for the treatment of neonatal pulmonary disease. Potential advantages in respiratory distress and aspiration syndromes, persistent pulmonary hypertension, pneumonia, as well as other entities are discussed. The experience with liquid ventilation to date indicates that this technology may significantly benefit many neonatal lung diseases. Documentation of its efficacy and safety is necessary, however, before this modality will assume in clinical medicine. PMID- 8510624 TI - Creative caring in the NICU: parent-to-parent support. AB - When infants are admitted to a neonatal intensive care unit, the parents are immediately confronted with the crisis surrounding a critically ill newborn and often require additional support. Parents experience feelings of anxiety, fear, anger, and guilt over this unanticipated event. In addition, parents often describe the withdrawal of friends and the denial responses of well-meaning family members during their infant's illness. In an effort to address the NICU parents' need for support, Butterworth Hospital in collaboration with Michigan State University initiated a demonstration and research project focused on parent to-parent support. The primary goal of the program is to improve parenting outcomes by providing emotional, informational, and role modeling support to parents of high-risk infants utilizing experienced volunteer parents. The program model includes professional program coordinators who recruit and train volunteer parents with past NICU experience. Volunteers are then matched to new NICU families based on infant's diagnosis, similar geographic location, and other characteristics. Volunteers provide support through hospital visits, phone contact, and home visits during the infant's hospitalization and throughout the infant's first year of life. The program was evaluated by analyzing the differences between a treatment group and a comparison group of parents. Significant differences between groups were found on measures of maternal mood states, maternal-infant relationships, and home environment. Services to over 900 families by 110 volunteer parents have convinced staff that the volunteer parents are a valuable and indispensable component of the services at Butterworth Hospital and that families of high-risk infants benefit from past experiences and ongoing support of volunteer parents. PMID- 8510626 TI - Mechanics of ventilation: compliance. PMID- 8510625 TI - Sibling education: implementing a program for the NICU. AB - Many nurses have recognized the need for sibling visitation and education in maternity units, but few sibling programs have been initiated for premature or ill infants. This article describes a model neonatal intensive care unit sibling education and visitation program that was designed and implemented by nurses practicing in a 60 bed NICU. The program strives to strengthen family functioning and bonding by involving siblings in the family experience of the hospitalization and care of a premature or ill infant. Over 100 children, ages three to eight years old, have attended the program since its inception and both the children and their parents have reported high levels of satisfaction with the program. Since the idea and implementation of NICU sibling education is so new, nursing research needs to be initiated in this area to determine the effectiveness of such programs. PMID- 8510627 TI - Instruments in neonatal research: measuring attachment behavior. PMID- 8510628 TI - Pediatric AIDS--Johns Hopkins grand rounds. PMID- 8510629 TI - Metoclopramide. PMID- 8510630 TI - CAT is coming. PMID- 8510631 TI - Clinically speaking--hot topics for gerontological nurses. PMID- 8510632 TI - Lead intoxication associated with chewing plastic wire coating--Ohio. PMID- 8510633 TI - Mortality among newly arrived Mozambican refugees--Zimbabwe and Malawi, 1992. PMID- 8510634 TI - Update: outbreak of hantavirus infection--southwestern United States, 1993. AB - Since May 1993, the New Mexico Department of Health, the Arizona Department of Health, the Colorado Department of Health, the Utah Department of Health, the Indian Health Service, and CDC, with the assistance of the Navajo Nation Division of Health, have been investigating an outbreak of illness associated with hantavirus infection. This report updates information regarding the relation between illness and infection with a previously unrecognized hantavirus. PMID- 8510635 TI - Update: mortality attributable to HIV infection/AIDS among persons aged 25-44 years--United States, 1990 and 1991. AB - During the 1980s, human immunodeficiency virus (HIV) infection emerged as a leading cause of death in the United States. This report updates national trends in deaths caused by HIV infection during 1990 and 1991 and indicates that HIV infection/acquired immunodeficiency syndrome (AIDS) continues to cause an increasing proportion of all deaths. PMID- 8510636 TI - Update: outbreak of hantavirus infection--southwestern United States, 1993. AB - An outbreak of illness associated with hantavirus infection continues to be investigated by state health departments in New Mexico, Arizona, Colorado, and Utah; the Indian Health Service; and CDC, with the assistance of the Navajo Nation Division of Health. This report updates information regarding the outbreak and presents information on two cases that occurred in the 10 months preceding this outbreak. PMID- 8510637 TI - Change in source of information: availability of Varicella vaccine for children with acute lymphocytic leukemia. PMID- 8510638 TI - Surveillance for diabetes mellitus--United States, 1980-1989. AB - PROBLEM/CONDITION: In the United States, diabetes mellitus is the most important cause of lower-extremity amputation and end-stage renal disease; the major cause of blindness among working-age adults; a major cause of disability, premature mortality, congenital malformations, perinatal mortality, and health-care costs; and an important risk factor for the development of many other acute and chronic conditions (e.g., diabetic ketoacidosis, ischemic heart disease, stroke). Surveillance data describing diabetes and its complications are critical to increasing recognition of the public health burden of diabetes, formulating health-care policy, identifying high-risk groups, developing strategies to reduce the burden of this disease, and evaluating progress in disease prevention and control. REPORTING PERIOD COVERED: In this report, data are summarized from CDC's diabetes surveillance system; trends in diabetes and its complications are evaluated by age, sex, and race for the years 1980-1989. DESCRIPTION OF SYSTEM: CDC has established an ongoing and evolving surveillance system to analyze and compile periodic, representative data on the disease burden of diabetes and its complications in the United States. Data sources currently include vital statistics, the National Health Interview Survey, the National Hospital Discharge Survey, and Medicare claims data for end-stage renal disease. RESULTS AND INTERPRETATION: In 1989, approximately 6.7 million persons in the United States reported that they had diabetes mellitus, and a similar number probably had this disabling chronic disease without being aware of it. The disease burden of diabetes and its complications is large and is likely to increase as the population grows older. Effective primary, secondary, and tertiary prevention strategies are needed, and these efforts need to be intensified among groups at highest risk, including blacks. Important gaps exist in periodic and representative data for describing the disease burden. ACTIONS TAKEN: CDC is assisting diabetes control programs in 26 states and one territory. These programs attempt to reduce the burden of diabetes by preventing blindness, lower extremity amputations, cardiovascular disease, and adverse outcomes of pregnancy among persons with diabetes. Because of important limitations in measuring the burden of diabetes, CDC is exploring sources of surveillance data for blindness, adverse outcomes of pregnancy, and the public health burden of diabetes among minority groups. PMID- 8510639 TI - Laboratory-based surveillance for meningococcal disease in selected areas, United States, 1989-1991. AB - PROBLEM/CONDITION: Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States. Accurate surveillance for meningococcal disease is required to detect trends in patient characteristics, antibiotic resistance, and serogroup-specific incidence of disease. REPORTING PERIOD COVERED: January 1989 through December 1991. DESCRIPTION OF SYSTEM: A case of meningococcal disease was defined by the isolation of N. meningitidis from a normally sterile site, such as blood or cerebrospinal fluid, in a resident of a surveillance area. Cases were reported by personnel in each hospital laboratory in the surveillance areas. The surveillance areas consisted of three counties in the San Francisco metropolitan area, eight counties in the Atlanta metropolitan area, four counties in Tennessee, and the entire state of Oklahoma. RESULTS: Age- and race-adjusted projections of the U.S. population suggest that approximately 2,600 cases of meningococcal disease occurred annually in the United States. The case-fatality rate was 12%. Incidence declined from 1.3/100,000 in 1989 to 0.9/100,000 in 1991. Seasonal variation occurred, with the highest attack rates in February and March and the lowest in September. The highest rates of disease were among infants, with 46% of cases affecting those < or = 2 years of age. Males accounted for 55% of total cases, with an incidence of 1.2/100,000, compared with 1.0/100,000 among females (relative risk (RR) = 1.3, 95% confidence interval (CI) 1.0-1.6). The incidence was significantly higher among blacks (1.5/100,000) than whites (1.1/100,000) (RR = 1.4 [95% CI 1.1-1.8]). Serogroup B caused 46% of cases and serogroup C, 45% Thirty-eight percent of isolates were reported to be resistant to sulfa; none were reported to be resistant to rifampin. INTERPRETATION: The decline in incidence of meningococcal disease from 1989 through 1991 cannot be explained by any change in public health control measures; this trend should be monitored by continued surveillance. The age, sex, and race distribution and seasonality of cases are consistent with previous reports. The proportion of N. meningitidis isolates resistant to sulfa continues to be substantial. A relatively small proportion of cases is potentially preventable by the use of the currently available polysaccharide vaccine, which induces protection against serogroups, A, C, Y, and W135 and is effective only for persons > 2 years of age. ACTIONS TAKEN: Current recommendations against the use of sulfa drugs for treatment or prophylaxis of meningococcal disease unless the organism is known to be sensitive to sulfa should be continued. Since resistance to rifampin is rarely reported, it continues to be the drug of choice for prophylaxis. The development of vaccines effective for infants and vaccines inducing protection against serogroup B would be expected to have a substantial impact on disease. PMID- 8510640 TI - Heat-stable and heat-labile thymidylate synthases B of Bacillus subtilis: comparison of the nucleotide and amino acid sequences. AB - Bacillus subtilis 168 is known to possess two thymidylate synthase (TSase; EC 2.1.1.45) genes: thyA and thyB. thyB encodes a thermosensitive TSase (inactivated at 46 degrees C) which, in wild-type cells, accounts for only 5-8% of the total cellular TSase activity. In order to investigate the thermal lability of TSaseB we have analyzed the thyB genes of B. subtilis 168 and of an unrelated strain B. subtilis ATCC6633, which is shown here to have a temperature-resistant TSaseB. This conclusion is supported by the frequency of appearance of spontaneous Thy- mutants at 37 degrees C and 46 degrees C, and by the analysis of clones containing the thyB genes from the two strains. The nucleotide sequences of these two thyB genes were compared. PMID- 8510641 TI - The mlo resistance alleles to powdery mildew infection in barley trigger a developmentally controlled defence mimic phenotype. AB - Recessive mlo resistance alleles of the Mlo locus in barley control a non race specific resistance response to infection by the obligate biotrophic fungus Erysiphe graminis f.sp. hordei. All the mlo alleles analysed stop fungal growth at the same developmental stage within a subcellularly restricted, highly localized cell wall apposition directly beneath the site of abortive fungal penetration. We report that near-isogenic lines carrying the alleles mlo1, mlo3 or mlo5 undergo dramatic spontaneous formation of cell wall appositions, not only in the absence of the fungal pathogen but also in sterile grown plants. A comparative study of spontaneous and infection-triggered cell wall appositions reveals a high degree of similarity with respect to structure, chemical composition and distinct localization within plant tissue. We show that the rate of spontaneous apposition formation is dependent on the genetic background of the plant and that its onset is under developmental control. Furthermore, spontaneous formation of wall appositions is specifically triggered by mlo alleles, since it is unaffected in the presence of the race-specific resistance allele Mlg. We propose a model for the function of the Mlo locus that suggests that both Mlo and mlo alleles control qualitatively the same apposition-based resistance mechanism, which, in the presence of the wild-type Mlo allele, is merely less efficient to provide protection against the currently common races of E. graminis f.sp. hordei. PMID- 8510642 TI - Genetic recombination in Bacillus subtilis 168: effect of recN, recF, recH and addAB mutations on DNA repair and recombination. AB - A recN- (recN1) strain of Bacillus subtilis was constructed. The effects of this and recF, recH and addAB mutations on recombination proficiency were tested. Mutations in the recN, recF, recH and addAB genes, when present in an otherwise Rec+ B. subtilis strain, did not affect genetic exchange. Strains carrying different combinations of mutations in these genes were constructed and examined for their sensitivity to 4-nitroquinoline-1-oxide (4NQO) and recombination proficiency. The recH mutation did not affect the 4NQO sensitivity of recN and recF cells and it only marginally affected that of addA addB cells. However, it reduced genetic recombination in these cells 10(2)- to 10(4)-fold. The addA addB mutations increased the 4NQO sensitivity of recF and recN cells, but completely blocked genetic recombination of recF cells and marginally affected recombination in recN cells. The recN mutation did not affect the recombinational capacity of recF cells. These data indicate that the recN gene product is required for DNA repair and recombination and that the recF, recH and addAB genes provide overlapping activities that compensate for the effects of single mutants proficiency. We proposed that the recF, recH, recB and addA gene products define four different epistatic groups. PMID- 8510643 TI - Induction of only one SOS operon, umuDC, is required for SOS mutagenesis in Escherichia coli. AB - The actions of UmuDC and RecA proteins, respectively in SOS mutagenesis are studied here with the following experimental strategy. We used lexAl (Ind-) bacteria to maintain all SOS proteins at their basal concentrations and then selectively increased the concentration of either UmuDC or RecA protein. For this purpose, we isolated operator-constitutive mutations oc in the umuDC and umuD'C operons and also used the oc98-recA mutation. The oc1-umuDC mutation prevents LexA repressor from binding to the operator and improves the Pribnow box consensus sequence. As a result, 5000 UmuD and 500 UmuC molecules per cell were produced in lexAl bacteria. This concentration is sufficient to restore SOS mutagenesis. The level of RecA protein present in the repressed state promoted full UmuD cleavage. Overproduction of RecA alone did not promote SOS mutagenesis. Increasing the level of RecA in the presence of high concentrations of UmuDC proteins has no further effect on SOS mutagenesis. We conclude that, after DNA damage, umuDC is the only SOS operon that must be induced in Escherichia coli to promote SOS mutagenesis. PMID- 8510644 TI - A general suppressor of RNA polymerase I, II and III mutations in Saccharomyces cerevisiae. AB - A multicopy genomic library of Saccharomyces cerevisiae (strain FL100) was screened for its ability to suppress conditionally defective mutations altering the 31 kDa subunit (rpc31-236) or the 53 kDa subunit (rpc53-254/424) of RNA polymerase III. In addition to allele-specific suppressors, we identified seven suppressor clones that acted on both mutations and also suppressed several other conditional mutations defective in RNA polymerases I or II. All these clones harbored a complete copy of the SSD1 gene. The same pleiotropic suppression pattern was found with the dominant SSD1-v allele present in some laboratory strains of S. cerevisiae. SSD1-v was previously shown to suppress mutations defective in the SIT4 gene product (a predicted protein phosphatase subunit) or in the regulatory subunit of the cyclic AMP-dependent protein kinase. We propose that the SSD1 gene product modulates the activity (or the level) of the three nuclear RNA polymerases, possibly by altering their degree of phosphorylation. PMID- 8510645 TI - Genetic characterization of the Pto locus of tomato: semi-dominance and cosegregation of resistance to Pseudomonas syringae pathovar tomato and sensitivity to the insecticide Fenthion. AB - The Pto locus governs resistance to bacterial speck disease in tomato caused by race 0 strains of Pseudomonas syringae pathovar tomato (Pst). Large populations segregating for the Pto locus were generated and genetically characterized. Analysis of the locus has revealed that Pto acts in a semi-dominant manner and cosegegrates with sensitivity to an organophosphorous insecticide, Fenthion, suggesting that Pto may be a complex locus responsible for both phenotypes. We have redefined its map position on chromosome five of the classical genetic map and assigned its position on the molecular map, thus facilitating the alignment of the two genetic maps of the short arm of chromosome five of tomato. Furthermore, we have screened random amplified polymorphic (RAPD) markers for their ability to differentiate near-isogenic lines that differ only with respect to Pto and have identified and mapped seven of these markers. Our results suggest that Pto may be located in a euchromatic region on chromosome five which will be advantageous for the cloning of this locus by one of several molecular strategies. PMID- 8510646 TI - Cloning and sequencing of a gene involved in the synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 3. AB - A 4.5 kb ScaI chromosomal DNA fragment of a clinical isolate of Streptococcus pneumoniae serotype 3 was cloned in Escherichia coli. Combined genetic and molecular analyses have allowed the localization, in a 781 bp EcoRV subfragment, of a gene (cap3-1) directly responsible for the transformation of an unencapsulated, serotype 3 mutant to the capsulated phenotype. Comparison of the deduced amino acid sequence of CAP3-1 with the protein sequences compiled in the data banks revealed that the CAP3-1 polypeptide was highly similar to the amino terminus of the GDP-mannose dehydrogenase of Pseudomonas aeruginosa, an enzyme that participates in the synthesis of the mucoid polysaccharide of this species. In addition, the 32 N-terminal amino acids of CAP3-1 perfectly matched structures common to NAD(+)-binding domains of many dehydrogenases. Our results indicate that the 4.5 kb ScaI fragment might also contain genes common to 13 different pneumococcal serogroups or serotypes tested. To the best of our knowledge, this is the first time that a gene of the capsular complex of S. pneumoniae has been cloned and sequenced. The findings reported here provide new insights for the study of the molecular biology of the main virulence factor responsible for the pathogenesis of pneumococcal infections and might represent a basic step in the identification of cross-reactive antigens that should allow the preparation of new and improved vaccines. PMID- 8510647 TI - Barley embryo globulin 1 gene, Beg1: characterization of cDNA, chromosome mapping and regulation of expression. AB - We report identification of a 2189 bp cDNA clone from barley corresponding to a single-copy gene, Beg1 (Barley embryo globulin), on chromosome 4, which encodes a storage globulin. In barley, the major protein reserve in the aleurone layer belongs to the 7S globulin class of proteins found in many seeds. Electrophoretically and antigenically similar proteins are present in the barley embryo. Accumulation of Beg1 mRNA was noted beginning 15-20 days post-anthesis in both the aleurone layer and embryo of the developing barley grain but not in the starchy endosperm. A high level of Beg1 mRNA is also present in the mature imbibed aleurones, which can be repressed by treatment with gibberellic acid. This repressive effect of gibberellin on the levels of Beg1 mRNA is confirmed in the gibberellin response-constitutive mutant, slender, whose aleurone layers do not accumulate Beg1 mRNA even in the absence of applied gibberellic acid. The deduced primary translation product of the Beg1 mRNA is a 63.7 amino acid (72 kDa) protein with homology to maize embryo globulin 1 (GLB1) and a partial sequence of a wheat 7S globulin. The internal amino acid sequence of BEG1 closely matches the N-terminal sequence of isolated barley aleurone globulin. Seven imperfect tandem repeats of 16 amino acids each are present near the N-terminus of BEG1, which conform to the consensus HGEGEREEEXGRGRGR, and contribute to the observed unusual amino acid composition of this protein. A second, distinct barley globulin gene, Beg2, which is homologous to maize Glb2, was detected by Northern and Southern analysis. Beg2 and Beg1 are regulated differently which may indicate variation in storage or utilization properties among the barley globulins. PMID- 8510648 TI - DNA methylation of sex chromosomes in a dioecious plant, Melandrium album. AB - Melandrium album, a dioecious plant species, has two heteromorphic sex chromosomes with the XY constitution typical for male and the XX for female plants. This plant represents an experimental model system of sex determination in which the Y chromosome plays a strongly dominant male role. We present data on the overall transcriptional activities of M. album sex chromosomes. DNA methylation patterns were analysed directly at the level of chromosomes using in situ nick-translation of fixed root mitotic chromosomes after nuclease digestion and in vivo labelling with S-adenosyl-L-[methyl-3H] methionine as donor of methyl groups. Both techniques revealed that the two X chromosomes of female plants had different levels of DNA methylation. Cell treatment with a DNA hypomethylating drug, 5-azacytidine, significantly influenced the labelling densities. These results imply that in female M. album plants, one of the two X chromosomes may be hypermethylated and inactive as described for mammalian cells (Lyon hypothesis). A similar analysis made on male cells displayed a similar relative levels of methylation in autosomes and sex chromosomes, thus indicating the transcriptional activity of both Y and X male chromosomes. PMID- 8510649 TI - Multiple regions of a divergent promoter control the expression of the Agrobacterium rhizogenes aux1 and aux2 plant oncogenes. AB - The two auxin biosynthesis genes, aux1 and aux2 of Agrobacterium rhizogenes strain A4, are located on opposite DNA strands with a short integenic region (394 bp) between their coding sequences. A functional analysis of this divergent promoter is presented. The transcription initiation sites of the two aux genes were determined and regions important for promoter activity were identified by deletion and transient expression analyses in tobacco protoplasts. The promoter activity of the aux intergenic region was demonstrated. A strong enhancer element contained within an 84 bp promoter fragment was identified. Far upstream regions were shown to have negative effects on the promoter activity of the short intergenic region. Interactions between positive elements in the intergenic region and negative effects of the upstream sequences may be the basis of strict control of the auxin biosynthesis necessary for the induction and maintenance of hairy root growth. PMID- 8510650 TI - Identification of a potential transcriptional regulator of hydrogenase activity in free-living Bradyrhizobium japonicum strains. AB - In Bradyrhizobium japonicum, Tn5 insertions in a particular chromosomal DNA fragment result in a Hup- phenotype in free-living conditions without affecting hydrogenase (Hup) activity in the symbiotic state. By determination of the nucleotide sequence of this region, we were able to identify the nature of the inactivated genes. The fragment is located 9 kb downstream of the hydrogenase structural genes and contains one incomplete and three complete open reading frames. They are designated hypD', hypE, hoxX and hoxA respectively, since the deduced amino acid sequences display very strong homology with genes involved in the regulation of hydrogenase activity in Escherichia coli, Rhodobacter capsulatus, Azotobacter vinelandii (hypD' and hypE) and Alcaligenes eutrophus (hoxX and hoxA). This is the first report on transcriptional activators of the hup genes in B. japonicum. Implications of these findings with respect to regulation of hydrogenase synthesis by hydrogen, oxygen and nickel in free-living B. japonicum are discussed. PMID- 8510651 TI - Intermolecular ligation mediates efficient cotransformation in Phytophthora infestans. AB - The processing of DNA molecules during transformation was characterized in the oomycete Phytophthora infestans. Linear and circular forms of non-replicating transformation vectors supported similar rates of stable transformation. Remarkably, digestion of plasmids within the selectable marker genes neomycin phosphotransferase (npt) or hygromycin phosphotransferase (hpt) had little effect on the recovery of drug-resistant transformants, and the cleaved sites were shown to be reconstituted in the transformants. An assay for the transient expression of beta-glucuronidase (GUS) in protoplasts treated with partial or disrupted GUS genes demonstrated that active genes could be reconstituted through intramolecular and/or intermolecular ligation between compatible ends, while incompatible ends were inefficiently joined. Stable transformation studies also demonstrated that complementing portions of incomplete npt or hpt genes joined through homologous recombination. Based on the indication of efficient ligation between DNA molecules during transformation, an efficient procedure for cotransformation was developed. The frequency of cotransformation between vectors expressing selected genes (npt or hpt) and nonselected sequences (GUS, beta galactosidase, or streptomycin phosphotransferase) approached unity when the plasmids were linearized with the same restriction enzyme before transformation. In contrast, cotransformation between circular plasmids or those cut with different enzymes occurred infrequently (10%). Hybridization analysis of DNA from cotransformants demonstrated that linearized plasmids became colocalized within genomic DNA, while circular plasmids typically inserted at unliked sites. PMID- 8510652 TI - Positively charged amino acids placed next to a signal sequence block protein translocation more efficiently in Escherichia coli than in mammalian microsomes. AB - Positively charged amino acids are known efficiently to block protein secretion in Escherichia coli, when placed within a short distance downstream of a signal sequence. It is not known whether the same applies to protein secretion in eukaryotic cells, though statistical studies of signal sequences of prokaryotic and eukaryotic secretory proteins have suggested that the situation may be different in this case. Here, we show that identical charge mutations in a model protein have different effects on membrane translocation in E. coli and in mammalian microsomes, and that the 'charge block' effect is much more pronounced in the prokaryotic system. This finding has implications not only for our understanding of the mechanisms of protein secretion, but also points to a potential problem in the expression of eukaryotic secretory proteins in bacteria. PMID- 8510653 TI - Genetic analysis of the X-chromosomal region 1E-2A of Drosophila melanogaster. AB - Reversion mutagenesis of three single P elements located in the cytogenetic interval 1E-2A at the tip of the X chromosome of Drosophila melanogaster was used to recover new deletions in this chromosomal region. The deletions obtained include small aberrations within region 2A and larger lesions extending from 2A into 1E and 1B. All three screens also yielded terminal deficiencies. The new deficiencies, together with previously characterized rearrangements, were analyzed for their complementation behaviour with the maternal effect locus fs(1) Nasrat and lethal loci in the region. These analyses provide an overall genetic map of the interval 1E-2A. In addition, the smaller deletions were physically mapped within cloned genomic DNA of the 2A region. PMID- 8510654 TI - Gene disruption in Lactobacillus plantarum strain 80 by site-specific recombination: isolation of a mutant strain deficient in conjugated bile salt hydrolase activity. AB - A chloramphenicol-resistance gene (cml) was introduced into the Lactobacillus plantarum gene encoding conjugated bile acid hydrolase (cbh) on a ColE1 replicon. This plasmid which is nonreplicative in Lactobacillus was used to transform L. plantarum strain 80. A homologous double cross-over recombination event resulted in replacement of the chromosomal cbh gene by the cml-containing cbh gene. The transformants obtained were unable to synthesize active conjugated bile acid hydrolase (Cbh). The Cbh- CmlR phenotype was stably maintained for more than 100 generations under nonselective conditions. PMID- 8510655 TI - Dual regulation by heat and nutrient stress of the yeast HSP150 gene encoding a secretory glycoprotein. AB - We have cloned and characterized the HSP150 gene of Saccharomyces cerevisiae, which encodes a glycoprotein (hsp150) that is secreted into the growth medium. Unexpectedly, the HSP150 gene was found to be regulated by heat shock and nitrogen starvation. Shifting the cells from 24 degrees C to 37 degrees C resulted in an abrupt increase in the steady-state level of the HSP150 mRNA, and de novo synthesized hsp150 protein. Returning the cells to 24 degrees C caused a rapid decrease in mRNA and protein synthesis to basal levels. The HSP150 5' flanking region contains several heat shock element-like sequences (HSE). To study the function of these sequences, a strain bearing a disrupted copy of the HSP150 gene was transformed with plasmids in which the coding region of HSP150, or a HSP150-lacZ fusion gene, was preceded by 5' deletion derivatives of the HSP150 promoter. Site-directed mutagenesis of one HSE-like element, located between the TATA box and transcription initiation sites, abolished heat activation of transcription. In addition to heat shock, the HSP150 gene is regulated by the availability of nutrients in the growth medium. The HSP150 mRNA level was increased by nitrogen limitation at 24 degrees C, even when under the control of a HSP150 promoter region of 137 bp carrying the mutagenized HSE. PMID- 8510656 TI - Inducible removal of UV-induced pyrimidine dimers from transcriptionally active and inactive genes of Saccharomyces cerevisiae. AB - The prior UV irradiation of alpha haploid Saccharomyces cerevisiae with a UV dose of 25 J/m2 substantially increases the repairability of damage subsequently induced by a UV dose of 70 J/m2 given 1 h after the first irradiation. This enhancement of repair is seen at both the MAT alpha and HML alpha loci, which are, respectively, transcriptionally active and inactive in alpha haploid cells. The presence in the medium of the protein synthesis inhibitor, cycloheximide in the period between the two irradiations eliminated this effect. Enhanced repair still occurred if cycloheximide was present only after the final UV irradiation. This indicated that the first result is not due to cycloheximide merely blocking the synthesis of repair enzymes associated with a hypothetical rapid turnover of such molecules. The enhanced repairability is not the result of changes in chromatin accessibility without protein synthesis, merely caused by the repair of the damage induced by the prior irradiation. The data clearly show that a UV inducible removal of pyrimidine dimers has occurred which involves the synthesis of new proteins. The genes known to possess inducible promoters, and which are involved in excision are RAD2, RAD7, RAD16 and RAD23. Studies with the rad7 and rad16 mutants which are defective in the ability to repair HML alpha and proficient in the repair of MAT alpha showed that in rad7, preirradiation enhanced the repair at MAT alpha, whereas in rad16 this increased repair of MAT alpha was absent. The preirradiation did not modify the inability to repair HML alpha in either strain. Thus RAD16 has a role in this inducible repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510657 TI - Physical organization of the upper pathway operon promoter of the Pseudomonas TOL plasmid. Sequence and positional requirements for XylR-dependent activation of transcription. AB - The upper pathway operon of the Pseudomonas putida TOL plasmid belongs to the 12/-24 class of promoters. These promoters exhibit three regions critical for regulated transcription, namely, the -12/-24 site for RNA polymerase/sigma 54 binding, the -55/-67 region for IHF protein binding, and the -130(UAS2)/ 170(UAS1) region, where two sites for XylR binding are located. The XylR protected G residues located at -131, -139, -160 and -169 were replaced with As, and the activity of the mutant promoters was assayed after fusion to a promoterless lacZ gene. The mutation (G(-169)-->A) resulted in a 50% decrease in expression from the promoter (Pu), whereas the other three changes had no significant effect. The XylR recognition sequence UAS2 has a perfect inverted repeat (5'-ATTTN4-AAAT-3') while UAS1 shows two mismatches (5'-CCTTN4AAAT-3'). The two Cs (located at -172 and -173), which interrupt the inverted repeat, were changed as follows: C(-172)-->T; C(-173)-->A, CC(-172, -173)-->AT. Transcription activation from the mutant promoters was measured as beta-galactosidase activity after fusion to lacZ; the better the palindromic sequence, the higher the rate of transcription from Pu, with increases in activity of up to 50%. The introduction of one or two full helix turns between the IHF and the XylR binding sites did not significantly affect transcription from Pu; however, the insertion of three helix turns resulted in a drop of 90% in the activity. The non-permissive effect of insertion of three full helix turns between the IHF and XylR binding sites was not evident in an IHF- background.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510658 TI - Identification and characterization of a chlorate-resistant mutant of Arabidopsis thaliana with mutations in both nitrate reductase structural genes NIA1 and NIA2. AB - Mutant plants defective in the assimilation of nitrate can be selected by their resistance to the herbicide chlorate. In Arabidopsis thaliana, mutations at any one of nine distinct loci confer chlorate resistance. Only one of the CHL genes, CHL3, has been shown genetically to be a nitrate reductase (NR) structural gene (NIA2) even though two NR genes (NIA1 and NIA2) have been cloned from the Arabidopsis genome. Plants in which the NIA2 gene has been deleted retain only 10% of the wild-type shoot NR activity and grow normally with nitrate as the sole nitrogen source. Using mutagenized seeds from the NIA2 deletion mutant and a modified chlorate selection protocol, we have identified the first mutation in the NIA1 NR structural gene. nia1, nia2 double mutants have only 0.5% of wild type shoot NR activity and display very poor growth on media with nitrate as the only form of nitrogen. The nia1-1 mutation is a single nucleotide substitution that converts an alanine to a threonine in a highly conserved region of the molybdenum cofactor-binding domain of the NR protein. These results show that the NIA1 gene encodes a functional NR protein that contributes to the assimilation of nitrate in Arabidopsis. PMID- 8510659 TI - SINE-like properties of a highly repetitive element in the genome of the obligate parasitic fungus Erysiphe graminis f.sp. hordei. AB - The genomic organization of repetitive DNA in the obligate parasitic fungus Erysiphe graminis DC ex Merat f.sp. hordei Em. Marchal was investigated using a cosmid library of the fungal genome. Three repetitive sequences were shown to be dispersed throughout the genome, and in a few cases they were found closely associated with long poly(dA) tracts. The most prevalent sequence is 903 bp long and accounts for at least 5% of the genome. Sequence analysis revealed features resembling mammalian Short INterspersed Elements (SINEs), namely the presence of a poly(dA) tail (33 bp), flanking direct repeats (13 bp), putative "A" and "B" blocks for RNA polymerase III binding; the corresponding transcript would be capable of forming a complex secondary structure. PMID- 8510660 TI - Structure and expression of the tobacco nuclear gene encoding the 33 kDa chloroplast ribonucleoprotein. AB - Tobacco chloroplasts contain a family of ribonucleoproteins (RNPs) which appear to be involved in mRNA processing and splicing in chloroplasts. We have characterized a new cDNA, 33k-6, potentially encoding a tobacco 33 kDa chloroplast RNP (cp33) homologue. This cDNA has a 78 bp insertion near the 3' end with respect to previously characterized cp33 cDNAs, leading to the creation of an alternative C-terminal sequence. The cp33 protein is encoded by a single-copy nuclear gene in Nicotiana sylvestris, which contains three introns. No typical TATA box is present in the upstream region of the gene. Multiple transcription start sites are often observed for promoters lacking TATA boxes, and have been suggested in the cp33 gene. Sequence comparison revealed that the 78 bp insertion in 33k-6 is derived from the third intron of the cp33 gene which is not removed during pre-mRNA splicing. Ribonuclease protection analysis showed that the processing of the third intron is slow compared to the other introns. A possible role for the partially spliced mRNA (cp33k-6) is discussed. PMID- 8510661 TI - Cloning and expression of the manganese superoxide dismutase gene of Escherichia coli in Lactococcus lactis and Lactobacillus gasseri. AB - The Escherichia coli sodA gene encoding the antioxidant enzyme Mn-containing superoxide dismutase (MnSOD), was cloned in the expression vector pMG36e. This vector has a multiple cloning site downstream of a promoter and Shine-Dalgarno sequences derived from Lactococcus. The protein-coding region of sodA from E. coli was amplified by the polymerase chain reaction, using a thermocycler and Taq DNA polymerase before cloning into pMG36e. When introduced into E. coli, the recombinant plasmid expressed the predicted fusion protein, both in the presence and absence of oxygen. The expression of the fusion protein in E. coli was verified by SOD assays, activity gels and Western blots. The recombinant plasmid was also introduced into Lactococcus lactis, which contains a resident SOD, and into Lactobacillus gasseri, which is devoid of SOD. Transformed lactococci expressed an active SodA fusion protein plus an active hybrid protein composed of subunits of the Lactococcus and the recombinant E. coli enzymes. Transformants of L. gasseri expressed only the fusion SodA protein, which was enzymatically active. PMID- 8510662 TI - Haploid and diploid expression of a Brassica campestris anther-specific gene promoter in Arabidopsis and tobacco. AB - The anther-specific cDNA clone Bcp1 from Brassica campestris is expressed in both the haploid pollen and diploid tapetum, as shown by in situ hybridization. We have isolated Bgp1, a genomic clone homologous to Bcp1. The coding region and extensive 5' flanking sequences of Bgp1 have been sequenced, and the coding region shows 88% identity with Bcp1. RNA gel blot analysis confirmed the expression of Bgp1-specific transcripts in B. campestris pollen. A 767 bp 5' DNA fragment was fused to the reporter gene beta-glucuronidase (gus) and introduced into both Arabidopsis thaliana and Nicotiana tabacum by transformation. This 5' fragment directed high-level expression in the pollen and tapetum of transgenic Arabidopsis. In transgenic tobacco however, the same construct was expressed only in pollen. A series of 5' deletion constructs has been created and used to transform A. thaliana to analyse the 5' region of Bgp1. The results indicate that Bgp1 expression in the tapetum and pollen of Arabidopsis requires the presence of different 5' DNA sequences. PMID- 8510663 TI - Molecular characterization and hrp dependence of the avirulence gene avrPto from Pseudomonas syringae pv. tomato [corrected]. AB - The avrPto avirulence gene from Pseudomonas syringae pv. tomato (Pst) race 0 governs race-specific resistance to bacterial speck disease in tomato cultivars containing the Pto resistance gene. The avrPto gene encodes 0.7 and 0.75 kb mRNAs whose predicted translation product is a mostly hydrophilic 164 amino acid protein of 18.3 kD a that reveals no homology to protein sequences in GenBank or EMBL databases. Highest expression of avrPto in cell culture is observed in minimal media containing sugars and sugar alcohols as carbon sources and lowest expression in minimal media containing tricarboxylic acid intermediates and in complex media. Expression of avrPto in planta is induced within 1 h following infection of both resistant and susceptible tomato plants by Pst, and increases over the first 6 h. Transcription of avrPto requires the hrpSR pathogenicity functions, but is independent of other Pst hrp genes. A region of the avrPto promoter shows homology to hrp box sequences upstream of other P. syringae genes that require the hrpSR locus for expression, and both avirulence activity and avrPto mRNA accumulation are abolished by deletions extending into this region. The avrPto transcription start site maps 31 nucleotides downstream of the hrp box motif. PMID- 8510664 TI - The fdx gene encoding the [2Fe--2S] ferredoxin of Halobacterium salinarium (H. halobium). AB - The gene encoding the [2Fe--2S] ferredoxin (fdx gene) was isolated from Halobacterium salinarium using two oligonucleotides deduced from the ferredoxin sequence as probes. Cosmid DNAs exhibiting hybridization were isolated, the fdx gene was localized to smaller subfragments and the nucleotide sequence determined. The 390 bp coding sequence is located in the halobacterial FI-DNA and transcribed as a 440 nucleotide mRNA. S1 mapping indicated that the 5' terminus of the mRNA maps immediately upstream of the ATG start codon. The promoter box A, centred around position -25 (5' AC-TATG 3'), and box B (TG) elements at the start of the transcript resemble the sequences of a typical archaeal promoter. The restriction pattern of an approximately 50 kb region surrounding the fdx gene is conserved in various Halobacterium species. The halobacterial ferredoxin and the major gas vesicle protein GvpA exhibit up to 70% similarity to their respective counterparts in cyanobacteria suggesting lateral gene transfer between the organisms. These similarities prompted a more detailed investigation of the relative positions of the genes in the halobacterial genome. PMID- 8510665 TI - Mutations in the mutY gene of Escherichia coli enhance the frequency of targeted G:C-->T:a transversions induced by a single 8-oxoguanine residue in single stranded DNA. AB - Oxidative damage to guanine in DNA results in the formation of 8-oxoguanine, which has been shown to induce G-->T transversions targeted to this site. The mutagenicity of this lesion was studied in several mutator strains of Escherichia coli, using single-stranded DNA containing a single 8-oxoguanine residue. The frequencies of targeted G-->T transversions increased markedly in mutY strains, while this mutagenic event was not affected in mutM or mutS strains. Introduction of a mutM mutation into a mutY strain caused a somewhat higher frequency of G-->T transversions than that in the mutY strain and the effect of a mutS mutation was marginal. We conclude that the mutY gene plays a crucial role in preventing targeted G-->T mutations derived from misreplication of the 8-oxoguanine containing template DNA. PMID- 8510666 TI - The role of penicillin-binding protein 3 (PBP 3) in cefotaxime resistance in Streptococcus pneumoniae. AB - A pneumococcal strain, with a reduced amount of penicillin-binding protein 3 (PBP 3), permitted an analysis of the role of this protein in cefotaxime resistance. We observed that reduced amounts of PBP 3 sensitize the bacteria to high temperature, to excess glycine and to some D-amino acids. These phenotypes suggest that the amount of PBP 3 may influence the membrane properties of the bacteria. The strain with reduced PBP 3 was transformed to cefotaxime resistance. We show that the PBP 3 mutation, in certain genetic backgrounds, decreases the level of resistance to cefotaxime by a factor of 2. Models are presented to explain this result. PMID- 8510667 TI - Comparison of the nucleotide sequences of the meta-cleavage pathway genes of TOL plasmid pWW0 from Pseudomonas putida with other meta-cleavage genes suggests that both single and multiple nucleotide substitutions contribute to enzyme evolution. AB - TOL plasmid pWW0 from Pseudomonas putida mt-2 encodes catabolic enzymes required for the oxidation of toluene and xylenes. The structural genes for these catabolic enzymes are clustered into two operons, the xylCMABN operon, which encodes a set of enzymes required for the transformation of toluene/xylenes to benzoate/toluates, and the xylXYZLTEGFJQKIH operon, which encodes a set of enzymes required for the transformation of benzoate/toluates to Krebs cycle intermediates. The latter operon can be divided physically and functionally into two parts, the xylXYZL cluster, which is involved in the transformation of benzoate/toluates to (methyl)catechols, and the xylTEGFJQKIH cluster, which is involved in the transformation of (methyl)catechols to Krebs cycle intermediates. Genes isofunctional to xylXYZL are present in Acinetobacter calcoaceticus, and constitute a benzoate-degradative pathway, while xylTEGFJQKIH homologous encoding enzymes of a methylphenol-degradative pathway and a naphthalene-degradative pathway are present on plasmid pVI150 from P. putida CF600, and on plasmid NAH7 from P. putida PpG7, respectively. Comparison of the nucleotide sequences of the xylXYZLTEGFJQKIH genes with other isofunctional genes suggested that the xylTEGFJQKIH genes on the TOL plasmid diverged from these homologues 20 to 50 million years ago, while the xylXYZL genes diverged from the A. calcoaceticus homologues 100 to 200 million years ago. In codons where amino acids are not conserved, the substitutions rate in the third base was higher than that in synonymous codons. This result was interpreted as indicating that both single and multiple nucleotide substitutions contributed to the amino acid-substituting mutations, and hence to enzyme evolution. This observation seems to be general because mammalian globin genes exhibit the same tendency. PMID- 8510669 TI - Parathyroid hormone in urinary stone patients. AB - To evaluate the role of parathyroids in calculus disease, the parathyroid hormone levels were determined in 22 control subjects and 42 stone (14 with bladder stone and 28 with kidney stone) patients. Serum calcium, inorganic phosphate, alkaline phosphatase and parathyroid hormone and urinary excretion of calcium and inorganic phosphate were determined. It was found that normocalcemic and normocalciuric stone patients had slightly higher levels of parathyroid hormone (irrespective of the site of the stone) and the difference was not statistically significant as compared with control subjects although some of the patients with calculus disease were hyperparathyroid. Serum alkaline phosphatase was increased while there was an increase in urinary calcium excretion in kidney stone patients and oxalate in all patients as compared with control subjects. The increase in inorganic phosphate was, however, not different from the control subjects. The subclinical hyperparathyroidism and stone formation in these patients are not correlated. PMID- 8510668 TI - The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. AB - We have identified a gene in Saccharomyces cerevisiae, MSH3, whose predicted protein product shares extensive sequence similarity with bacterial proteins involved in DNA mismatch repair as well as with the predicted protein product of the Rep-3 gene of mouse. MSH3 was obtained by performing a polymerase chain reaction on yeast genomic DNA using degenerate oligonucleotide primers designed to anneal with the most conserved regions of a gene that would be homologous to Rep-3 and Salmonella typhimurium mutS. MSH3 seems to play some role in DNA mismatch repair, inasmuch as its inactivation results in an increase in reversion rates of two different mutations and also causes an increase in postmeiotic segregation. However, the effect of MSH3 disruption on reversion rates and postmeiotic segregation appears to be much less than that of previously characterized yeast DNA mismatch repair genes. Alignment of the MSH3 sequence with all of the known MutS homologues suggests that its primary function may be different from the role of MutS in repair of replication errors. MSH3 appears to be more closely related to the mouse Rep-3 gene and other similar eukaryotic mutS homologues than to the yeast gene MSH2 and other mutS homologues that are involved in replication repair. We suggest that the primary function of MSH3 may be more closely related to one of the other known functions of mutS, such as its role in preventing recombination between non-identical sequences. PMID- 8510670 TI - Expression of constitutive heat shock protein-70 in normal (non-stressed) rabbit urinary bladder tissue. AB - The expression of constitutive HSP-70 in the urinary bladder was determined by SDS-PAGE and western blotting using a mouse monoclonal antibody against HSP-70. The western blot analysis showed that the mouse anti-HSP-70 cross-reacted with a 70 kDa protein present in the extracts of the urinary bladder muscle and mucosa. Densitometric scanning of the western blots allowed us to specifically quantitate the relative amounts of the HSP-70. The quantitation of the HSP-70 by combining immunoblotting and densitometry using a laser scanner is reproducible and this technique requires only a small amount of tissue. The amounts of HSP-70 can be estimated from a standard curve of nanogram(ng) of HSP-70 vs absorption from the immunoblots. The amounts of HSP-70 in the muscular and mucosal layers in the body of the urinary bladder are more than those in the base of the bladder. The presence of HSP-70 in the muscle and mucosal epithelium of the bladder was demonstrated by immunohistochemical analysis of freshly removed tissue from the base and the body of bladder from normal animals. PMID- 8510671 TI - A novel phenomenon of burst of oxygen uptake during decavanadate-dependent oxidation of NADH. AB - Oxidation of NADH by decavanadate, a polymeric form vanadate with a cage-like structure, in presence of rat liver microsomes followed a biphasic pattern. An initial slow phase involved a small rate of oxygen uptake and reduction of 3 of the 10 vanadium atoms. This was followed by a second rapid phase in which the rates of NADH oxidation and oxygen uptake increased several-fold with a stoichiometry of NADH: O2 of 1:1. The burst of NADH oxidation and oxygen uptake which occurs in phosphate, but not in Tris buffer, was prevented by SOD, catalase, histidine, EDTA, MnCl2 and CuSO4, but not by the hydroxyl radical quenchers, ethanol, methanol, formate and mannitol. The burst reaction is of a novel type that requires the polymeric structure of decavanadate for reduction of vanadium which, in presence of traces of H2O2, provides a reactive intermediate that promotes transfer of electrons from NADH to oxygen. PMID- 8510672 TI - Liver collagen of rats submitted to chronic intoxication with acetaldehyde. AB - It was found that chronic intoxication of rats with acetaldehyde results in a distinct, progressive increase of 5-3H-proline incorporation into collagen synthesized by liver. At the same time biosynthesis of other proline-containing (noncollagenous) proteins does not change significantly. On the other hand the collagen content in the rat liver did not increase in the early stage of acetaldehyde administration, but increased when acetaldehyde feeding was continued for 6 months. About 40% increase of total collagen content was found in livers of the intoxicated animals. All the investigated collagen types (I, III, IV and V) grew in the same degree. No changes in proportional relationships between collagens of different types were found. PMID- 8510673 TI - Individual amino acid balances in young lean and obese Zucker rats fed a cafeteria diet. AB - The amino acid composition of the diet ingested by reference and cafeteria diet fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet. Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids. In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age-or size-of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the 'blueprint for growth' which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accruing protein with high rates throughout. Diet composition--and not protein availability or quality--induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity. There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both 'models' of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization. PMID- 8510674 TI - Biochemical and electron microscopy analysis of the endotoxin binding to microtubules in vitro. AB - The mechanisms involved in cellular activation and damage by bacterial endotoxins are not completely defined. In particular, there is little information about possible intracellular targets of endotoxins. Recently, the participation of a microtubule associated protein in endotoxin actions on macrophages has been suggested. In the present work, we have studied the effect of E. coli lipopolysaccharide on the polymerization of microtubular protein in vitro. Electrophoretic analysis of the polymerization mixtures showed that the endotoxin inhibited the polymerization when present at high concentrations. At lower concentrations, LPS selectively displaced the microtubule associated protein MAP 2 from the polymerized microtubules. Electron microscopy showed that LPS binds to microtubules of tubulin + MAPs and to microtubules of purified tubulin (without MAPs) polymerized with taxol. Gel filtration experiments confirmed the binding of LPS to tubulin, and by ligand blot assays an interaction LPS-MAP-2 was detected. The ability of LPS to interact with microtubular proteins suggests a possible participation of microtubules on the cellular effects of endotoxins. PMID- 8510675 TI - Calpain processing of brain microtubules from the Atlantic cod, Gadus morhua. AB - Microtubules isolated from Atlantic cod (Gadus morhua) brains retained assembly competence and ultraculture, although treatment with rabbit calpain resulted in loss of MAPs. In addition, spirals and aberrant structures formed when calpain I was activated post assembly. No such effect was seen with calpain II. Soluble fractions from cod brain were found to contain proteolytic activity that could be blocked by exogenously added calpastatin. Calpain was also isolated from cod muscle tissue with 10 times less yield, compared to rabbit lung. On the basis of Ca(2+)-requirements for activation in the mM range, electrophoretic mobility, antigenicity and hydrophobicity, we conclude that the proteolytic activity was attributable to calpain II. There was no difference in effects of rabbit and cod calpain II on cod microtubule proteins, indicating that calpain is a conserved protein. Our results suggest that calpains might be involved in the Ca(2+) dependent irreversible regulation of cod brain microtubules. PMID- 8510676 TI - Fractionation of erythroblasts with affinity-mediated modifications of their electrical properties using counter-current distribution. AB - We have previously reported the possibility of modifying the electrical properties of cells by means of their interaction with a specific ligand carrying a polyelectrolyte (Anal Biochem 200: 280-285). This selective modification of receptor-containing cells changed their partition in a charge-sensitive aqueous two-phase system. We here present the fractionation of electrically modified erythroblasts by the use of an automatic multiple-partition procedure, counter current distribution. The cells were fractionated according to the degree of differentiation of erythroblasts as evaluated from the hemoglobin content as well as the relative activities of the two enzymes, 3-phosphoglycerate kinase and bisphospho-glycerate mutase. PMID- 8510677 TI - [DNA-methylating system of chicken liver nuclei under normal conditions and in viral transformation]. AB - The DNA methylating system of cellular nuclei from intact or virus transformed chicken liver was studied. The presence of multiple forms of methylases different in hydrophobic properties and isoelectric focusing points has been proved. The isoelectrofocusing made it possible to differentiate between the enzymes methylating preferably nonmethylated in vitro or methylated in vivo DNA. The DNA methylases pool contains both types of methylases (de novo and supporting ones) in intact cells and at neoplastic transformation, however, the specificity of methylation and level of several enzymes in transformed cells is changed in the direction of broad specificity and lower activity. The general level of methylase activity at viral transformation is by 18-20% lower, while the content of 5 methylcytosine in hepatoma cells DNA is twofold lower as compared with the content in the DNA of intact cells. PMID- 8510678 TI - [Immunobiological characteristics of Brucella outer membrane proteins, genetic determinants of which are expressed in Escherichia coli cells]. AB - The influence of the brucella OMP preparations obtained by the genetic engineering technique (18, 38 and 18 + 38 kD) on the formation of the specific protection and progress of infectious process in brucellosis in the in vivo experiments has been studied. The OMPs synthesized in Escherichia coli cells GSE579 and having mol mass 18 and 38 kD are common antigens for a number of brucella species. The 18 kD OMP was found to protect 66.7% of experimental animals against brucellosis, while the protection by the commercial live vaccine was 78.0%. The 38 kD OMP did not possess the protective activity with the index of infectivity in the experimental group of animals being higher than the one in the control group (77.9% and 53.4% respectively). The indexes of colony forming units in the mice spleen were also higher in the experimental group of animals. The obtained results suggest that the 38 kD OMP may be a factor of brucella virulence. PMID- 8510679 TI - [Synthesis, cloning, and determination of the primary structure of a full-length DNA copy of the gene for influenza A/Alma-Ata/1417/84 virus (H1N1-serovariant HSW1N1) hemagglutinin]. AB - The full-length copy of the hemagglutinin gene RNA of the influenza virus A/Alma Ata/1417/84 (Hsw1 N1-serovariant) has been synthesized and cloned on Escherichia coli plasmid pBR327. The complete nucleotide sequence of the cloned DNA copy was determined by the Maxam-Gilbert procedure. The predicted amino acid, sequence of HA1 hemagglutinin subunit was compared with the sequences of HA1 subunits from other H1N1-subtype influenza virus strains. It has been found that the structure of the HA1-subunit of the studied strain is most similar to the structure of the identical region of the A/New Jersey/18/76 hemagglutinin. PMID- 8510680 TI - [Suppression of replication of swine parvoviral antisense RNA against the NS PPV gene in swine thyroid gland cells]. AB - The possibility of suppression of porcine parvovirus (PPV) reproduction in the culture of thyroid gland cells of a swine that contain the integrated genes for asRNA against the nonstructural proteins of the virus has been studied. 10 cell lines with the asRNA genes have been obtained. The line with the maximal number of integrated gene copies was used to inflict with the parvovirus. The expression of asRNA in this cell line was shown to lead to 95% suppression of PPV replication as compared with the control cell line. PMID- 8510681 TI - [Peptide thermostable enterobacterial toxins (genetic control, structure, mechanism of action, testing)]. AB - The structure and functional specificity of thermostable toxins, their genetic determination, mechanisms of action and testing are reviewed. Amino acid sequences of the peptide toxins with the common amino acid residues on the C-end of their molecules are presented as well as the sequences of the functional groups underlying the biological activity. The data on the structure of precursors of enterotoxins, the genetic control of toxin production and location of the est-genes in the genome of bacteria are demonstrated. The nature of receptors binding enterotoxins, their effect on the guanylate-cyclase system are also described. The possibility of enterotoxins testing by different techniques (genetic, biological, immunological) are discussed. PMID- 8510682 TI - [Preparation of a non-defective adenovirus vector based on the Ad5 genome with the E3 region replaced with plasmid DNA with a kanamycin- resistance gene]. AB - The plasmid pH5KV14 containing the right end of the Ad5 viral genome (45-100 map units) with deleted nonessential E3 region (78.5-84 map units) has been constructed. A helper-independent recombinant virus Ad5KV14 has been obtained as a result of in vivo transformation of the line 293 human cells by the pH5KV14 plasmid DNA and an EcoRI-A DNA fragment of the virus Ad5 and subsequent recombination. A nondefective recombinant virus Ad5KV17 containing the Ad5 genome with the E3 region substituted for the plasmid DNA fragment coding for the kanamycin-resistance has been constructed by a similar procedure. PMID- 8510684 TI - [Study of genomic polymorphism of Shigella flexneri strains, isolated in various geographic regions]. AB - Strains of Shigella flexneri isolated from patients in 4 geographic regions of the former USSR have been studied by plasmid analysis and fingerprinting techniques. It has been shown that these methods make possible to differentiate phenotypically identical strains for 9 genotypic patterns (7 different plasmid profiles and 3 specific hybridization patterns). Strains of Shigella flexneri isolated from each region possess the similar hybridization patterns independent of serovar and plasmid profiles. Similar hybridization patterns were found among the strains isolated in Erevan and Dushanbe. The strains isolated in Kiev are related to Erevan and Dushanbe strains, but they also possess the specific additional hybridization bands. Tashkent isolates are different from the strains isolated in other geographic regions. They are also of clonal origin in spite of the different serovars and plasmid profiles registered for these strains. Positive correlation has been found between serovar and plasmid profile characteristics of the strains. The clonal origin of the Tashkent isolates is different from the one of Erevan, Dushanbe and Kiev isolates, the latter having a similar clonal origin. PMID- 8510683 TI - [Structural and molecular-biological characteristics of a new transducing phage from Bacillus thuringiensis Tt 91]. AB - A new bacteriophage Tt91 of larger size and broad lytical spectrum has been isolated from soil to widen the possibility to study new Bacillus thuringiensis strains. The Tt91 bacteriophage was shown to perform the intravariant transduction and, thus, can be used for genetic mapping. The ultrastructural analysis made it possible to refer bacteriophage Tt91 to morphotype A1 and showed similarity of Tt91 morphological structure to the one of CP-group bacteriophages. The performed comparative analysis of phage-specific proteins has confirmed a possible relation of the bacteriophages and revealed the differences between them. The data on the resistance of Tt91 DNA to majority of site-specific restriction endonucleases (17 out of 18 tested) and on DNA melting in the wide interval of temperatures suggests the presence of possible anomalies in the Tt91 DNA. PMID- 8510685 TI - Images in clinical medicine. Three-dimensional CT diagnosis of maxillofacial trauma. PMID- 8510686 TI - The increasing disparity in mortality between socioeconomic groups in the United States, 1960 and 1986. AB - BACKGROUND: There is an inverse relation between socioeconomic status and mortality. Over the past several decades death rates in the United States have declined, but it is unclear whether all socioeconomic groups have benefited equally. METHODS: Using records from the 1986 National Mortality Followback Survey (n = 13,491) and the 1986 National Health Interview Survey (n = 30,725), we replicated the analysis by Kitagawa and Hauser of differential mortality in 1960. We calculated direct standardized mortality rates and indirect standardized mortality ratios for persons 25 to 64 years of age according to race, sex, income, and family status. RESULTS: The inverse relation between mortality and socioeconomic status persisted in 1986 and was stronger than in 1960. The disparity in mortality rates according to income and education increased for men and women, whites and blacks, and family members and unrelated persons. Over the 26-year period, the inequalities according to educational level increased for whites and blacks by over 20 percent in women and by over 100 percent in men. In whites, absolute death rates declined in persons of all educational levels, but the reduction was greater for men and women with more education than for those with less. CONCLUSIONS: Despite an overall decline in death rates in the United States since 1960, poor and poorly educated people still die at higher rates than those with higher incomes or better educations, and this disparity increased between 1960 and 1986. PMID- 8510688 TI - Privilege and health--what is the connection? PMID- 8510687 TI - Educational status and active life expectancy among older blacks and whites. AB - BACKGROUND AND METHODS: Persons of low socioeconomic status are known to have reduced life expectancy. In a study of the relation of socioeconomic status to disability-free or active life expectancy among older persons, we analyzed prospectively gathered data on 2219 blacks and 1838 whites who were 65 years of age or older in the Piedmont region of North Carolina. We defined disability as the inability to perform independently one or more basic functional activities such as walking, bathing, dressing, eating, and using the toilet. For subgroups defined by sex, race, and education, statistical models were used to estimate, for persons at each year of age, the probability of transition from not being disabled or being disabled at base line to not being disabled, being disabled, or having died one year later. These transition probabilities were then entered into increment-decrement life tables to generate estimates of total, active, and disabled life expectancy (with total life expectancy equal to active life expectancy plus disabled life expectancy). RESULTS: Sixty-five-year-old black men had a lower total life expectancy (11.4 years) and active life expectancy (10 years) than white men (total life expectancy, 12.6 years; active life expectancy, 11.2 years), although the differences were reduced after we controlled for education. The estimates for 65-year-old black women (total life expectancy, 18.7 years; active life expectancy, 15.9 years) were similar to those for white women. Black men and women 75 years old and older had higher values for total life expectancy and active life expectancy than whites, and the differences were larger after stratification for education. Education had a substantially stronger relation to total life expectancy and active life expectancy than did race. At the age of 65, those with 12 or more years of education had an active life expectancy that was 2.4 to 3.9 years longer than the values for those with less education in all the four subgroups defined by sex and race. Overall, the subgroups with longer total life expectancy and active life expectancy also lived more years with a disability. CONCLUSIONS: Among older blacks and whites, the level of education, a measure of socioeconomic status, has a greater effect than race on total life expectancy and active life expectancy. PMID- 8510689 TI - Idiopathic membranous nephropathy--to treat or not to treat? PMID- 8510690 TI - Non-anticoagulant uses of heparin. PMID- 8510691 TI - Toward a social policy for health. PMID- 8510692 TI - Drug-resistant tuberculosis in New York City. PMID- 8510693 TI - Drug-resistant tuberculosis in New York City. PMID- 8510694 TI - Drug-resistant tuberculosis in New York City. PMID- 8510695 TI - Directly observed treatment of tuberculosis. PMID- 8510696 TI - The law and control of tuberculosis. PMID- 8510697 TI - The law and control of tuberculosis. PMID- 8510698 TI - Serum cholesterol in young men and cardiovascular disease. PMID- 8510699 TI - Thromboxane synthase and organ preference for metastases. PMID- 8510700 TI - The end stage renal disease program. PMID- 8510701 TI - The end stage renal disease program. PMID- 8510702 TI - The end stage renal disease program. PMID- 8510703 TI - The end stage renal disease program. PMID- 8510704 TI - Long-term treatment of trichotillomania (hair pulling) PMID- 8510705 TI - Mortality rates and risk factors for coronary disease in black as compared with white men and women. AB - BACKGROUND: Currently recognized risk factors for coronary artery disease have been identified primarily from investigations of white populations. In this investigation, we estimated mortality rates for coronary disease and for any cause and identified risk factors for death from coronary disease among whites and blacks. METHODS: Data collected over a 30-year period in the Charleston Heart Study were used to estimate mortality rates and quantify associations with risk factors assessed at the base-line examination in 1960 and 1961 of 653 white men, 333 black men, 741 white women, and 454 black women. RESULTS: There were no significant racial differences in the rate ratios for death from coronary disease; however, women had significantly lower death rates than men. Over the 30 year period, the mortality rates for coronary disease per 1000 person-years were 5.2 for white men (95 percent confidence interval, 4.1 to 6.3), 4.6 for black men (3.0 to 6.2), 2.1 for white women (1.6 to 2.6), and 3.2 for black women (2.3 to 4.0). Significant, or nearly significant, predictors of mortality due to coronary disease were systolic blood pressure in all four groups; serum cholesterol level among white men, white women, and black women; and smoking among white men, white women, and black men. Although the difference was not statistically significant, the risk of death from coronary disease was consistently increased among diabetics in all four groups. A higher level of education was predictive of lower rates of death due to coronary disease among white men and black women. For all causes of death taken together, the rates for blacks were higher than the rates for whites. The presence of hypertension, a history of smoking, and a history of diabetes were significant or nearly significant predictors of mortality from any cause in all four groups. CONCLUSIONS: Although the rates of death from coronary disease were somewhat lower among black men than white men and higher among black women than white women, the black:white mortality rate ratios were not statistically significant, and the major risk factors for mortality from coronary disease were similar in blacks and whites in the 30-year follow-up of the Charleston Heart Study. PMID- 8510706 TI - A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. AB - BACKGROUND: Phenobarbital, once widely prescribed to prevent febrile seizures, is now in disfavor because of its side effects and lack of efficacy. Diazepam, administered only during episodes of fever, may be a safe, effective agent to prevent the recurrence of febrile seizures. METHODS: We conducted a randomized, double-blind, placebo-controlled trial among 406 children (mean age, 24 months) who had at least one febrile seizure. Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesses. RESULTS: During a mean follow-up of 1.9 years (a period during which 90 percent of febrile seizures recur), our intention-to-treat analysis showed a reduction of 44 percent in the risk of febrile seizures per person-year with diazepam (relative risk = 0.56; 95 percent confidence interval, 0.38 to 0.81; P = 0.002). A survival analysis of the length of time to the first recurrent febrile seizure did not show a significant difference between the treatment groups (P = 0.064 by the log-rank test), but after adjustment for covariates, diazepam was found to have a benefit (P = 0.027 by Cox regression analysis). An analysis restricted to children who had seizures while actually receiving the study medication (7 in the diazepam group and 29 in the placebo group) showed an 82 percent reduction in the risk of febrile seizures with diazepam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.37; P < 0.001). Of the 153 children who took at least one dose of diazepam, 39 percent had ataxia, lethargy, or irritability or at least one other moderate side effect that was reversed after a reduction in the dose. There were no severe side effects. CONCLUSIONS: Oral diazepam, given only when fever is present, is safe and reduces the risk of recurrent febrile seizures. PMID- 8510707 TI - Prognosis of untreated patients with idiopathic membranous nephropathy. AB - BACKGROUND: Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. METHODS: We prospectively studied 100 consecutive patients (68 men and 32 women; mean [+/- SD] age, 51 +/- 17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. RESULTS: Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed, and they required dialysis. As calculated by the Kaplan-Meier method, the estimated probability (+/- the standard error of the estimate) of retaining adequate kidney function was 88 +/- 5 percent after five years and 73 +/- 7 percent after eight years. The prognosis was poorer in men and in patients over 50 years of age, but not in patients with the nephrotic syndrome, hypertension, or hypercholesterolemia. CONCLUSIONS: Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission. These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy. PMID- 8510708 TI - Preventing bronchoconstriction in exercise-induced asthma with inhaled heparin. AB - BACKGROUND: We have previously reported that inhaled heparin prevents allergic bronchoconstriction in sheep and inhibits the anti-IgE-mediated release of histamine from mast cells in vitro. Since the release of such mediators has been implicated in exercise-induced asthma, we investigated whether inhaled heparin could also attenuate the bronchoconstrictor response in this disease. METHODS: On five days we studied 12 subjects with a history of exercise-induced asthma. On day 1 they underwent a standardized exercise challenge on a treadmill to document the presence of exercise-induced asthma. Minute ventilation was estimated with a calibrated respiratory inductive plethysmograph. The workload was increased until the heart rate reached 85 percent of the predicted maximal value, and was sustained for 10 minutes. The magnitude of bronchoconstriction was assessed by measuring specific airway conductance before and after the exercise. On day 2 the partial-thromboplastin time was measured in plasma obtained before and after the subjects inhaled a nebulized solution of heparin (1000 U per kilogram of body weight). On days 3 through 5 the subjects were pretreated with 4 ml of inhaled heparin (1000 U per kilogram), cromolyn sodium (20 mg), or placebo according to a single-blind, randomized, crossover design and underwent exercise challenge 45 minutes later. To exclude the possibility that heparin had any direct effect on airway smooth muscle, bronchial provocation with histamine was induced in five subjects on two further days after pretreatment with either heparin or placebo. RESULTS: Inhaled heparin and cromolyn sodium had no effect on specific airway conductance at base line, but did attenuate the exercise-induced decreases in this variable: the mean (+/- SE) maximal decrease five minutes after exercise was 9 +/- 5 percent after pretreatment with heparin, as compared with 22 +/- 5 percent after pretreatment with cromolyn and 35 +/- 2 percent after pretreatment with placebo. Heparin did not change the partial-thromboplastin time and did not modify the bronchoconstrictor response to histamine. CONCLUSIONS: Inhaled heparin prevents exercise-induced asthma without influencing histamine-induced bronchoconstriction. This non-anticoagulant action of heparin is more likely to be related to a modulation of mediator release than to a direct effect on smooth muscle. PMID- 8510710 TI - Rapeseed meal-glucosinolates and their antinutritional effects. Part 1. Rapeseed production and chemistry of glucosinolates. AB - This review, which will be presented in seven parts is concerned with the use of rapeseed meal as an animal feeding stuff. The presence of glucosinolates in the meal limits its use due to a number of antinutritional and physiological effects. Whilst not in itself exhaustive, this review updates earlier reviews by reference to recent papers on the above topics. In this first paper the history of the crop and the current production situation are presented and the nature of glucosinolates and methods for their analysis are reviewed in order to facilitate a better appreciation of the problems referred in later sections. PMID- 8510709 TI - Charcot-Marie-Tooth disease type 1A. Association with a spontaneous point mutation in the PMP22 gene. AB - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. CMT type 1A is associated with a 1.5-megabase DNA duplication in region p11.2-p12 of chromosome 17 in most patients. An increased dosage of a gene within the duplicated segment appears to cause the disease. The PMP22 gene, which encodes a myelin protein, has been mapped within the duplication and proposed as a candidate gene for CMT type 1A. METHODS: We analyzed DNA samples from a cohort of 32 unrelated patients with CMT type 1 who did not have the 1.5-Mb tandem duplication in 17p11.2-p12 for mutations within the PMP22 coding region. Molecular techniques included the polymerase chain reaction (PCR), heteroduplex analysis to detect point mutations, and direct nucleotide-sequence determination of amplified PCR products. RESULTS: A 10-year old boy was identified with a point mutation in PMP22, which resulted in the substitution of cysteine for serine in a putative transmembrane domain of PMP22. Analysis of family members revealed that the PMP22 point mutation arose spontaneously and segregated with the CMT type 1 phenotype in an autosomal dominant pattern. The patients with the PMP22 point mutation had clinical and electrophysiologic phenotypes that were similar to those of patients with the 1.5 Mb duplication. CONCLUSIONS: The PMP22 gene has a causative role in CMT type 1. Either a point mutation in PMP22 or a duplication of the region including the PMP22 gene can result in the disease phenotype. PMID- 8510711 TI - Effect of rabadi fermentation on phytic acid and in vitro digestibility of barley. AB - Rabadi, an indigenous fermented food, was prepared by mixing cereal flour with buttermilk, allowing it to ferment at 30, 35 and 40 degrees C for 6, 12, 18, 24 and 48 h and cooking the fermented mixture for 0.5 h with continuous stirring. Two types of rabadi were prepared i.e. autoclaved and unautoclaved. In autoclaved type of rabadi cereal flour was mixed with water, autoclaved (0.103 MPa = 15 psi for 15 min), cooled, mixed with buttermilk and fermented. As this type of rabadi was precooked prior to fermentation, hence, the fermented product did not require cooking afterwards, while in unautoclaved rabadi, barley flour and buttermilk were mixed, fermented and then cooked prior to consumption. Phytic acid was reduced drastically at all the temperatures and periods of fermentation in both autoclaved and unautoclaved type of rabadi; greater reduction occurred at higher temperature and duration of fermentation. A significant improvement in the in vitro digestibility of starch and protein was observed; maximum improvement was noticed when fermentation was carried out at 40 degrees C for 48 h in both the types of rabadi. Phytic acid had a significant (P < 0.05) negative correlation with digestibility (in vitro) of proteins and starch of barley flour rabadi. PMID- 8510712 TI - [The effect of gamma radiation on the methionine and tryptophan content of soy protein products]. AB - Effect of gamma irradiation on the content of methionine and tryptophan in soya protein products were investigated. Irradiation with doses of 1, 3 and 5 kGy caused significant (p = 0.05) decrease of methionine contents. Parallel with the decrease in methionine also the relative quality of proteins is lowered. Tryptophan content were significantly reduced (p = 0.05) at irradiation doses of 3 and 5 kGy. The relative decrease of methionine and tryptophan contents are significantly correlated (p = 0.05) with relative increase in amount of products by the irradiation induced oxidation of lipids; correlation coefficients were 0.576 and 0.715. PMID- 8510713 TI - Kinetic analysis of the loss of some B-vitamins during the cooking of macaroni. AB - The kinetics of the losses of thiamin, niacinamide, and riboflavin were investigated during the cooking of macaroni at 50, 75, 80, 85, and 90 degrees C. Simultaneous analysis of the vitamins was achieved by HPLC using a mu-Bondapak column. The activation energies for the losses of thiamin, niacinamide, and riboflavin were determined as 25 kJ/mol, 22 kJ/mol, and 11 kJ/mol, respectively. It was concluded that the leaching of these vitamins into cooking water was the main pathway for their loss during macaroni preparation. PMID- 8510714 TI - Influence of bitter gourd (Momordica charantia) on growth and blood constituents in albino rats. AB - Feeding of bitter gourd (Momordica charantia) at 0.02, 0.1 and 0.5% (dry weight) levels in a semi-synthetic diet for a period of 8 weeks did not have any adverse influence on the food intake, growth and organ weights of normal adult rats. The haematological parameters of these experimental rats were also normal. Serum cholesterol levels of the rats receiving 0.5% bitter gourd were significantly lower than those of the control rats. There was no hypoglycaemic effect of bitter gourd in these normoglycaemic rats. PMID- 8510716 TI - Shifting the emphasis. PMID- 8510715 TI - Dependence of biological response on the geometric and electronic characteristics of phenol derivatives with smoke flavour. AB - On the base of the data of conformational analysis and quantum-chemical calculation (method CNDO/2) of the series of phenol derivatives with smoke flavour it was shown that the structural fragment responsible for the odorant activity consists of the oxygen atom and two hydrogen atoms. The atomic orbitals of these atoms are constituting the highest occupied molecular orbital (HOMO) with the high values of the orbital coefficients of their 2p pi- and 1s-orbitals. The distance between the hydrogen atoms is 1.7-2.5 A, while the average distance (L) from these hydrogen atoms to the oxygen atom is 5.45 +/- 0.85 A. The dependence between the value of psychological response for the presence of the studied compounds within the gaseous phase and the value L was found. PMID- 8510717 TI - Head lice--pediculosis capitis. PMID- 8510718 TI - Women power in rural Africa. PMID- 8510719 TI - Self care for cancer patients. PMID- 8510720 TI - [Detecting leprosy]. PMID- 8510721 TI - Discontent among intensive care nurses. PMID- 8510722 TI - The importance of teamwork in health care. PMID- 8510723 TI - Clinical research versus "evaluation". PMID- 8510724 TI - Infection control aspects of enteral feeds. PMID- 8510725 TI - [Collective bargaining and trade unions in nursing]. AB - Nurses are apparently striving towards collective bargaining in order to meet their professional and personal needs. The reasons might be rapid social change and dissatisfaction with values and norms imposed on them. Although the nursing profession has been represented by a professional association since 1914, interest in labour unions is increasing. Various factors, such as administrative practices, support the interest in labour unions. Although labour unions promise a utopia to potential members, membership leads to advantages and disadvantages both for the profession and the individual. PMID- 8510726 TI - President calls on the profession to move forward. PMID- 8510727 TI - Acute mediastinitis. PMID- 8510728 TI - Contraceptives and informed consent. PMID- 8510729 TI - Hunger and appetite is there a difference? PMID- 8510730 TI - Pain management. Part One: An historical overview. PMID- 8510732 TI - [How can research in practice help?]. PMID- 8510731 TI - [Collective bargaining and trade unions. 2: Trade union activities]. PMID- 8510733 TI - [Dynamic nursing service management]. PMID- 8510734 TI - Scabies--Sarcoptes scabiei. PMID- 8510735 TI - Wound healing update. PMID- 8510737 TI - Using saliva to test for HIV. PMID- 8510736 TI - The lessons of laughter. PMID- 8510738 TI - [Midwifery in the early 20th century]. PMID- 8510739 TI - Tobacco abuse in Africa. PMID- 8510740 TI - Hillary Clinton lobbies at Hopkins for health. PMID- 8510741 TI - UK rejects call for more systematic biology cash. PMID- 8510742 TI - Stanford seeks life after Cohen-Boyer patent expires. PMID- 8510743 TI - Opportunistic infection. PMID- 8510744 TI - Opposition to oncomouse. PMID- 8510745 TI - NIH funding. PMID- 8510746 TI - Give the hunger-striker a break. PMID- 8510748 TI - Palaeoanthropology. Four legs good, two legs better. PMID- 8510747 TI - Neuropsychology. The scratchpad of the mind. PMID- 8510749 TI - Loss of kinase activity. PMID- 8510750 TI - No HMG-1 box signature. PMID- 8510751 TI - Crystal structure of cyclin-dependent kinase 2. AB - Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell cycle. The crystal structures of the human CDK2 apoenzyme and its Mg2+ ATP complex have been determined to 2.4 A resolution. The structure is bi-lobate, like that of the cyclic AMP-dependent protein kinase, but contains a unique helix-loop segment that interferes with ATP and protein substrate binding and probably plays a key part in the regulation of all cyclin-dependent kinases. PMID- 8510752 TI - Spatial working memory in humans as revealed by PET. AB - The concept of working memory is central to theories of human cognition because working memory is essential to such human skills as language comprehension and deductive reasoning. Working memory is thought to be composed of two parts, a set of buffers that temporarily store information in either a phonological or visuospatial form, and a central executive responsible for various computations such as mental arithmetic. Although most data on working memory come from behavioural studies of normal and brain-injured humans, there is evidence about its physiological basis from invasive studies of monkeys. Here we report positron emission tomography (PET) studies of regional cerebral blood flow in normal humans that reveal activation in right-hemisphere prefrontal, occipital, parietal and premotor cortices accompanying spatial working memory processes. These results begin to uncover the circuitry of a working memory system in humans. PMID- 8510753 TI - Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination. AB - Among site-directed DNA recombination systems, V(D)J recombination is noteworthy in that identical reactants yield different recombination products at the junction of joined segments. This variation is the basis for diversity at the base of antigen receptor binding pockets and corresponds to V-(D)-J DNA junctions. An abundance of certain junctions has been noted. It has been proposed that these junctions are favoured because they occur where short regions of homology in participating coding ends might align preferentially. Here we use a system that is entirely free from cellular selection to show that the diversity of coding joints can be severely restricted when the coding ends participating in the reaction have short regions of homology. This constraint on diversity is diminished but not eliminated by terminal deoxynucleotidyl transferase, a mechanistic feature that has implications for the establishment of the immune repertoire. PMID- 8510754 TI - Activation of complement by an IgG molecule without a genetic hinge. AB - The hinge region links the two Fab arms to the Fc portion of the IgG molecule. It mediates flexibility to the molecule and serves as a connecting structure between the two heavy chains. In addition it provides space between the Fab and Fc parts. All three properties have been proposed to be important for the ability of IgG to initiate complement activation leading to complement-mediated cell lysis (CML). Here we report the construction of a hinge-deleted mouse-human chimaeric IgG3 molecule with specificity for the hapten NIP (3-iodo-4-hydroxy-5 nitrophenacetyl), HM-1. HM-1 lacks the genetic hinge, but has an introduced cysteine between Ala 231 (EU numbering) and Pro 232 in the lower hinge encoded by the CH2 exon. The introduced cysteine forms a disulphide bond between the two heavy chains of the molecule. In CML, HM-1 shows a greater activity than IgG3 wild type. This is the first time an IgG molecule without a genetic hinge has been found to be active in CML. We conclude that the hinge functioning as a spacer is not a prerequisite for complement activation. Rather, its major role seems to be to connect the heavy chains to each other in the amino-terminal part of CH2. Because HM-1 is expected to have low Fab-Fc flexibility, this molecular feature is probably of no importance for complement activation. PMID- 8510755 TI - Segmental organization of embryonic diencephalon. AB - The diencephalon is a complex integration centre and intricate relay station of the vertebrate brain. Its development involves the generation of great cellular diversity and neuronal specificity. We report here that it becomes organized in steps, through a stereotyped sequence of neuromeric subdivisions. Diencephalic neuromeres define four cellular domains (D1-D4) that can be followed throughout development, each unit contributing to a well defined part of the adult structural pattern. We propose that the segmental identity of each diencephalic unit is specified by a unique combination of genes, maintained by polyclonal cell lineage restrictions. A comparison of vertebrate and arthropod development suggests that the basic principles that control anterior axial patterning and set up neuronal specificity in the embryonic central nervous system are highly conserved in evolution. PMID- 8510756 TI - Protein kinase C is required for light adaptation in Drosophila photoreceptors. AB - Protein kinase C (PKC) is a key enzyme for many cellular processes but its physiological roles are poorly understood. An excellent opportunity to investigate the function of PKC has been provided by the identification of an eye specific PKC in Drosophila and a null PKC mutant, inaCP209 (refs 5,6). Bright conditioning lights delivered to inaC photoreceptors lead to an abnormal loss of sensitivity in whole cell recordings from dissociated ommatidia; this has been interpreted as 'hyper-adaptation' and PKC's role has been suggested to be distinct from light adaptation. A presumably related finding is that during intense light, the response of inaC declines to baseline. Invertebrate photoreceptors use the phosphoinositide signalling cascade, responding to single photons with so-called quantum bumps which sum to form the macroscopic response to light. Light adaptation allows photoreceptors to adjust their sensitivity over the enormous range of ambient intensities. Although the molecular mechanism of light adaptation remains obscure, it is a negative-feedback process mediated by a rise in cytosolic calcium and a decrease in bump size. We now show that under physiological conditions light adaptation is severely reduced in inaC, suggesting that eye-specific PKC, itself activated by a rise in cytosolic calcium and diacylglycerol, is required for adaptation. Furthermore, we show that in the absence of PKC individual bumps fail to terminate normally, an effect that can account for the pleiotropic manifestations of the inaC phenotype. PMID- 8510757 TI - A conserved mitotic kinase active at late anaphase-telophase in syncytial Drosophila embryos. AB - Mutations in the Drosophila gene polo cause abnormal mitotic and meiotic divisions. This gene encodes a 577-amino-acid protein that has an N-terminal putative kinase domain and a 300-residue C-terminal domain. In budding yeast, a homologous kinase is encoded by CDC5 (ref. 3), a gene required for nuclear division late in the mitotic cycle and during meiosis. Murine homologues have also been described. Here we show that the polo gene product immunoprecipitated from extracts of single Drosophila embryos can phosphorylate casein in vitro, and that the kinase activity peaks cyclically at late anaphase/telophase. This contrasts with the cyclical activity of cyclin B-associated p34cdc2 kinase, which is maximal upon entry into mitosis during the rapid cycles of mitosis in the syncytium. PMID- 8510758 TI - Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. AB - Human myxoid liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation. PMID- 8510759 TI - New eukaryotic transcriptional repressors. AB - Transcriptional activating sequences have been described that are encoded by parts of the genome of Escherichia coli. These acidic peptides, fused to a DNA binding fragment of the yeast transcriptional activator GAL4, activate transcription of a gene in a wide array of eukaryotes, provided that gene bears GAL4-binding sites nearby. Here we describe an E. coli-encoded sequence that, when attached to the same DNA-binding fragment (GAL4(1-147)), converts that fragment into a repressor. Thus, as assayed in yeast or in vitro in yeast extracts, this molecule represses transcription when bound upstream of a variety of different activators. Two additional repressing regions that work when tethered upstream, a multiple mutant derivative of the original isolate and a synthetic peptide are, like the original isolate, highly basic. At least one activator can be inhibited by the mutant but not by the parental repressing region. These and other findings suggest that these repressing regions interact with and inhibit the activity of activating regions bound nearby on DNA. PMID- 8510760 TI - [Lemurs of Madagascar. Tests on evolution of primate communities]. AB - The flora and fauna of Madagascar evolved rather independently from the African mainland. In contrast to other oceanic islands, Madagascar is large enough to house most major components of tropical ecosystems, allowing tests of evolutionary hypotheses on the level of complete communities. Taking lemurs, the primates of Madagascar, as an example, evolutionary hypotheses correctly predict the organization of their community structure with respect to ecological correlates. Lemur social systems and their morphological correlates, on the other hand, deviate largely from the typical mammalian pattern. Thus, the traditional hypotheses of behavioral ecology, based solely on resource distribution and predation pressure, are insufficient to explain the existing variability in lemur social systems. Other factors, such as activity patterns and avoidance of infanticide, may be equally important. Due to interspecific variation in these characters, lemurs offer the unique opportunity to determine the relative importance of these factors for the evolution of social systems. PMID- 8510761 TI - A genetic fossil: protamine gene as a primordial gene. PMID- 8510762 TI - Evolution of eusociality in the Bathyergidae. The case of the giant mole rats (Cryptomys mechowi). PMID- 8510763 TI - The 5-HT1A receptor selective ligands, (R)-8-OH-DPAT and (S)-UH-301, differentially affect the activity of midbrain dopamine neurons. AB - The effects of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2(di-n propylamino)tetralin [(R)-8-OH-DPAT] and the novel 5-HT1A antagonist (S)-5-fluoro 8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-301] were studied with regard to the firing pattern of single mesencephalic dopamine (DA) neurons with extracellular recording techniques in chloral hydrate anesthetized male rats. Neuronal activity was studied with respect to firing rate, burst firing and regularity of firing. In the ventral tegmental area (VTA) low doses of (R)-8-OH-DPAT (2-32 micrograms/kg i.v.) caused an increase in all three parameters. The effect on firing rate of DA neurons was more pronounced in the parabrachial pigmentosus nucleus than in the paranigral nucleus, the two major subdivisions of VTA. In the substantia nigra zona compacta (SN-ZC), (R)-8-OH-DPAT (2-256 micrograms/kg i.v.) had no effect on firing rate and regularity of firing and only slightly increased burst firing. High doses of (R)-8-OH-DPAT (512-1024 micrograms/kg i.v.) decreased the activity of DA cells in both areas, an effect that was prevented by pretreatment with the selective DA D2 receptor antagonist raclopride. (S)-UH-301 (100-800 micrograms/kg i.v.) decreased both firing rate and burst firing without affecting regularity of DA neurons in the VTA. In the SN-ZC, (S)-UH-301 decreased the firing rate but failed to affect burst firing and regularity of firing. These effects of (S)-UH-301 were blocked by raclopride pretreatment. Local application by pneumatic ejection of 8-OH-DPAT excited the DA cells in both the VTA and the SN-ZC, whereas (S)-UH-301 inhibited these cells when given locally. These results show that 5-HT1A receptor related compounds differentially affect the electrophysiological activity of central DA neurons. The DA receptor agonistic properties of these compound appear to contribute to the inhibitory effects of high doses of (R)-8-OH-DPAT and (S)-UH-301 on DA neuronal activity. Given the potential use of 5-HT1A receptor selective compounds in the treatment of anxiety and depression their effects on central DA systems involved in mood regulation and reward related processes are of considerable importance. PMID- 8510765 TI - Evidence for uptake2-mediated O-methylation of noradrenaline in the human amnion FL cell-line. AB - The uptake and metabolism of 3H-noradrenaline has been examined in the FL cell line derived originally from human amnion. Cell cultures metabolised 3H noradrenaline (1.0 mumol/l) to 3H-normetanephrine and, to a lesser extent, to metabolites (not distinguished) of the O-methylated deaminated fraction; primary deaminated metabolites were not detected. 3H-normetanephrine formation a) was not saturable in the noradrenaline concentration range 0.2-150 mumol/l, b) was decreased to 20%-30% of control levels by uptake2 inhibitors (O methylisoprenaline, 20 and 100 mumol/l; cimetidine, 10 mumol/l; hydrocortisone, 200 mumol/l) and c), was almost insensitive to uptake1 inhibitors (cocaine, 30 mumol/l; desipramine, 3 mumol/l). Uptake of noradrenaline was manifested after 30 minutes as a 6-fold increase in the cell content of the amine following inhibition of catechol-O-methyl transferase, either alone or in conjunction with inhibition of monoamine oxidase. Uptake was decreased maximally to 40% of control levels by O-methylisoprenaline. IC50 values for inhibition of the O methylisoprenaline-sensitive component of uptake were (in mumol/l): corticosterone (0.3), papaverine (1.1), O-methylisoprenaline (3.0), cimetidine (6.0), (-)noradrenaline (460), and tetraethylammonium (2230). Except for the last agent, for which a comparative value is not available, the IC50's are in good agreement with those for inhibition of uptake2 in the Caki-1 cell-line reported by other investigators. The component of uptake resistant to O-methylisoprenaline was depressed by papaverine (a 50% decrease at 50 mumol/l), but was not affected by the other uptake2 inhibitors or by cocaine (30 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510764 TI - Extraneuronal uptake and O-methylation of 3H-adrenaline in the rabbit aorta. AB - The influence of uptake2 inhibitors on the O-methylation and accumulation of 3H adrenaline by the isolated rabbit aorta was studied. Strips were incubated with 0.05 mumol/l 3H-(-)-adrenaline during 15 min. Monoamine oxidase and uptake1 were inhibited and the 3H-adrenaline present in the tissue was measured as well as the metabolites found in the tissue and in the incubation fluid. In another series of experiments, monoamine oxidase, uptake1 and catechol-O-methyl transferase (COMT) were inhibited, and tritium accumulation was measured in the tissue. When COMT was inhibited, inhibitors of uptake2 produced a maximal reduction of 3H adrenaline accumulation that did not exceed 50%. When COMT was intact, inhibitors of uptake2 diminished total 3H-removal and, more markedly, O-methylation and concomitantly increased the tissue content of 3H-adrenaline. Mineralocorticoids (corticosterone and deoxycorticosterone acetate) inhibited 3H-adrenaline uptake (when COMT was inhibited) and 3H-metanephrine formation (when COMT was functional) as effectively as did sexual steroids (17-beta-oestradiol, progesterone and testosterone); hydrocortisone (hemisuccinate or phosphate) had no effect (for concentrations up to 120 mumol/l). At the end of the incubation some strips were washed out with amine-free solution. Compartmental analysis of the efflux showed that the amine had distributed into three extraneuronal compartments (compartment I, II and III, with half times of 0.4, 4 and 15 min, respectively). Corticosterone (120 mumol/l) decreased the amount of 3H-adrenaline in compartment III and simultaneously increased the amount of the amine in compartment I (extracellular space).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510766 TI - 1,1'-diethyl-2,2'-cyanine (decynium22) potently inhibits the renal transport of organic cations. AB - The excretion of cationic compounds by renal proximal tubule cells involves at least two distinct transporters: the basolateral type which transports organic cations from the plasma into the proximal tubule cell, and the apical type which secretes the organic cations into the lumen of the tubule. However, potent inhibitors were known for neither type of transporter. Here we introduce a compound, decynium22, that potently, competitively, and selectively inhibits the apical type of the renal organic cation transporter. The transport of the prototypical organic cation 14C-tetraethylammonium through the apical plasma membrane of clonal proximal tubule cells (LLC-PK1) was used as experimental system. Initial rates of 14C-tetraethylammonium transport into LLC-PK1 cells were saturable, the Km and Vmax being 27 mumol/l and 200 pmol/(mg protein.min), respectively. Decynium22 competitively and potently inhibited 14C tetraethylammonium transport (Ki = 5.6 nmol/l). Moreover, the effect of decynium22 on basolateral to apical directed transepithelial transport of 14C tetraethylammonium through a confluent monolayer of LLC-PK1 cells was determined. Decynium22 (30 nmol/l) applied to the apical medium, reduced transepithelial transport by 76% and increased intracellular accumulation of 14C tetraethylammonium 1.5-fold. In contrast, application of 30 nmol/l decynium22 to the basolateral medium failed to affect transepithelial transport and intracellular accumulation of 14C-tetraethylammonium. Decynium22 is the most potent inhibitor of the renal transport of organic cations known so far. With decynium22 it is now possible to distinguish precisely between a decynium22 sensitive apical type and a decynium22-resistant basolateral type of renal organic cation transporter in renal proximal tubule cells. PMID- 8510767 TI - Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes. AB - Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes. After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/l) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mumol/l) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 mumol/l) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow. The findings suggest that approximately 45% of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function. PMID- 8510768 TI - Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and on mRNA levels in rat brain. AB - The effect of long-term oral treatment with caffeine on A1 and A2 receptors in the rat brain was studied. Caffeine was added to the drinking water and the animals were sacrificed after a 12 day treatment period. The plasma caffeine concentration was close to 100 microM. A1 receptors were studied using quantitative autoradiography with [3H]cyclohexyladenosine (CHA). Caffeine treatment increased the number of A1 receptors in the CA3 subfield of the hippocampus from 337 to 393 fmol/mg with no change in KD (0.692 vs. 0.675 nM). A1 mRNA was measured using Northern blots and quantitative in situ hybridization. There was no increase in A1 mRNA. A2a receptors, located in dopamine rich regions of the rat brain, were studied with quantitative autoradiography using [3H]CGS 21680 as the ligand, and the A2a mRNA was determined using quantitative in situ hybridization. Caffeine treatment produced no significant change in either receptor number or mRNA, even though the apparent Bmax tended to increase from 322 +/- 8 to 352 +/- 8 fmol/mg. The results show that treatment with caffeine in a dose that causes tolerance to several effects of caffeine and increases some effects of adenosine analogues increases the number of A1 receptors without any change in A1 mRNA, suggesting that the adaptive changes are at a post translational level. There were no significant changes in A2 receptors indicating that the two types are regulated differently and/or that the amount of endogenous agonist is sufficient to regulate A1, but not A2 receptors. PMID- 8510769 TI - Amiodarone--induced changes in surfactant phospholipids of rat lung. AB - Amiodarone HCl (AD) is a very effective antiarrhythmic drug, but its use is often associated with serious pulmonary complications. It is shown to induce lung phospholipidosis. Nevertheless, the effects of this drug on pulmonary surfactant which is composed of about 75% phospholipids and which prevents alveolar collapse is not known. Therefore, we have examined the effect of AD on the intra- and extracellular surfactant pools and on the levels of phosphatidylcholine (PC), the primary constituent of pulmonary surfactant. Male Wistar rats were fed AD (175 mg/kg) by oral gavage for three weeks. At the end of the experimental period, the rats were killed, the lungs removed and perfused, and surfactant isolated. Some lungs were prepared for ultrastructural examination. Phospholipid was assayed in the intra- and extracellular surfactant. Amiodarone produced a significant increase in both the intra- and extracellular surfactant phospholipid along with an appreciable change in the phospholipid profile. Also, the drug seemed to increase the number of lamellar inclusions in the surfactant producing type II alveolar cells. These data suggest that administration of AD leads to an increase in the lung surfactant phospholipid levels and lamellar bodies in alveolar type II cells. PMID- 8510770 TI - Role of Na+ and protein kinase C in angiotensin desensitization and tachyphylaxis in the guinea-pig ileum. AB - Simultaneous recordings of the tension and intracellular Ca2+ concentration of guinea-pig ileum longitudinal smooth muscle strips, as well as 24Na+ and 45Ca2+ influx measurements in cultured myocytes from the same tissue, were used to investigate the mechanisms underlying angiotensin-induced desensitization and tachyphylaxis. Angiotensin II and [2-lysine]-angiotensin II (Lys2All), incubated for prolonged periods (10 min) with muscle strips, induced fading of the contractile response (desensitization) and reappearance of the intracellular Ca2+ concentration oscillations, which were inhibited during the initial increase in cytosolic Ca2+. The desensitization was paralleled, in cultured myocytes, by inhibition of the 45Ca2+ but not of the 24Na+ influxes which were initially stimulated by the peptides. On the other hand, repeated administrations of angiotensin II (but not of Lys2All) caused gradual reduction of the contractile response and of the 24Na+ influx stimulation evoked by the agonist (tachyphylaxis). Treatment with phorbol 12-13 dibutyrate accelerated the desensitization induced by both angiotensin II and by Lys2All and aggravated the tachyphylaxis to angiotensin II. The results support the hypothesis that activation of protein kinase C is responsible for the desensitization and that tachyphylaxis is due to the slow dissociation of angiotensin II from a postulated Na(+)-dependent regulatory site on the receptor. PMID- 8510771 TI - BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery. AB - Potassium (K+) channel openers decrease intracellular free Ca2+ concentrations ([Ca2+]i by hyperpolarizing the membrane and deactivating the Ca(2+)-channels. To examine whether the hyperpolarization produced by K(+)-channel openers has other effects on the mechanical activity of vascular smooth muscle, we investigated the effects of levcromakalim (BRL 38227) on membrane potential, [Ca2+]i, as measured with fura-2, and force of contraction induced by 30 mmol/l KCl-physiological salt solution (PSS), in canine coronary arteries. BRL 38227 hyperpolarized the membrane and reduced increases in [Ca2+]i and in contractile force induced by 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined in the presence of BRL 38227, was located to the right of the control curve determined by decreasing extracellular Ca2+ concentrations ([Ca2+]o) in 30 mmol/l KCl-PSS. The [Ca2+]i-contractile force curve, determined by decreasing extracellular K+ concentrations ([K+]o), was also located to the right of that determined by decreasing [Ca2+]o in 30 mmol/l KCl-PSS. The effect of BRL 38227, a reduction in the Ca(2+)-sensitivity of contractile elements, was antagonized by the ATP sensitive K(+)-channel blocker, glibenclamide (10(-6) or 10(-5) mol/l). These results suggest that the membrane hyperpolarization induced by BRL 38227, or the repolarization caused by reducing [K+]o, decreases the Ca(2+)-sensitivity of contractile elements of vascular smooth muscle. PMID- 8510772 TI - Mechanisms of action of 7-O-ethyl tetrandrine in isolated vascular smooth muscle of the rabbit aorta. AB - Tetrandrine is an alkaloid from a Chinese herb which has been used to treat hypertension in humans. The mechanism(s) of its antihypertensive action is not clear. The goal of this study was to examine the direct effects of a derivative of tetrandrine, 7-O-ethyl tetrandrine (TD), on vascular smooth muscle. In particular, the goals were to study (1) the involvement of the endothelium in the responses of isolated aortic rings to TD, and (2) the effects of TD at intracellular sites involved in muscle contraction in skinned aortic strips treated with saponin. TD (1-100 mumol/l) decreased noradrenaline (NA) and K(+) evoked contraction of isolated aortic rings with or without endothelium in a concentration-dependent manner although to a lesser degree with the K(+)-evoked contraction. In NA-contracted rings, the IC50 for TD was approximately 28-30 mumol/l, at which a 20% decrease in K(+)-force development of aortic rings was observed. The slope of the concentration-relaxation curve was steeper in aortic rings with endothelium than without endothelium (1.09 vs. 0.88) in NA-contracted rings. TD increased tone in acetylcholine (ACh)-relaxed rings but did not change the force in aortic rings relaxed by sodium nitroprusside (NaNP) or ATP. In TD pretreated rings, TD blocked ACh-induced relaxation, but not NaNP or ATP-induced relaxation. In skinned aortic strips, TD decreased Ca2+ uptake by the SR (IC50 approximately 77.4 mumol/l, slope = 0.88), did not affect Ca2+ release from the SR, and decreased Ca2+-activation of the contractile proteins at 300 mumol/l TD. PMID- 8510773 TI - The good physician. What should we be, Sir William? PMID- 8510774 TI - Mammoscam. PMID- 8510775 TI - Breast cancer malpractice litigation in North Carolina, 1984-1992. PMID- 8510776 TI - Domestic violence--a health crisis. PMID- 8510777 TI - Extreme lateral lumbar disc herniation. Diagnosis and management. AB - Extreme lateral disc herniation accounts for about 10% of lumbar disc ruptures and is more common in the elderly. Patients will frequently complain of pain in the groin and anterior thigh but little if any back pain. Because the L4 root is often involved, the physical exam often shows quadriceps weakness and a diminished patellar reflex. Other important signs include a negative Laseque's sign and reproduction of pain with lateral bending of the back toward the involved extremity. Currently, CT or MRI are the diagnostic procedures of choice. The initial treatment for extreme lateral disc herniation is bed rest and NSAIDs with surgery if conservative therapy fails. Primary care physicians should consider extreme lateral disc herniation when they evaluate patients with low back and leg pain. PMID- 8510778 TI - Durham, City of Medicine, USA. Part 1: The genesis. PMID- 8510779 TI - Love potion number 8 1/2. Gamma-hydroxybutyrate poisoning. PMID- 8510780 TI - RBRVS in a private practice medical community. PMID- 8510781 TI - [Is cannabis always a soft drug?]. PMID- 8510782 TI - [Qinghaosu (artemisinine), Chinese herb against multi-resistant malaria parasite; also important for The Netherlands]. PMID- 8510783 TI - [The ATP-sensitive potassium channel: function and potential for pharmacological modification]. PMID- 8510784 TI - [The quality of ambulance transportation between regional hospitals and a central hospital]. AB - We studied the quality of ambulance transport of critically ill and wounded patients between rural hospitals and a referral centre (so-called secondary transport). The study group comprised all patients transported in the course of one year from a rural hospital in the southwestern part of the Netherlands to a centre hospital in Rotterdam (n = 59). Their records were reviewed retrospectively. A distinction was made between patients whose vital functions were acutely threatened before transport and patients in whom this was not the case. Results show that 24% of all patients were transferred inadequately. The inadequately transferred patients all belonged to the group in whom vital functions were acutely threatened. Frequently occurring shortcomings concerned oxygenation and intravenous lines. It is concluded that medical assistance by a specialist is indicated with all secondary transports, because it is difficult to predict if vital functions will be threatened during transport. Further research may be directed at the question which mode of transportation (ambulance or helicopter) is suited for long-distance interhospital transport. PMID- 8510785 TI - [The value of ultrasonography consultation by second-line gynecological caregivers to midwives and family practitioners]. AB - OBJECTIVE: Evaluation of a consulting hour for ultrasound examination for general practitioners and midwives, performed by gynaecologists. STUDY DESIGN: Prospective. METHOD: Indications for ultrasound examination, as determined by general practitioners and midwives, were compared with the ultrasound findings. The consequences of the ultrasound examination were analysed. RESULTS: An abnormal finding was obtained in 23.5% of 1801 women examined by ultrasound. Correction of estimated gestational age took place in 47%. Abnormal findings were present in 64% of women with first trimester bleeding. In 5.6% a further consultation of a gynaecologist was necessary. CONCLUSION: A consulting hour for ultrasound examination is a useful supplementary diagnostic tool for general practitioners and midwives. PMID- 8510786 TI - [Hearing impairment in nursing home patients not easily screened when relying on nurses' and patients' opinions]. AB - OBJECTIVE: To assess the diagnostic value of the opinion of the nursing staff and the patients themselves about hearing impairment of somatic nursing home patients. DESIGN: Descriptive. SETTING: Nursing Home and Rehabilitation Centre Amstelhof in Amsterdam. METHOD: All newly admitted patients in the period October 1989 to mid-May 1990 were asked to give an opinion about their hearing; the nursing staff were asked for an opinion as well. The results of these two measurements were compared with the results of the screening audiogram, used as the gold standard. For both the nursing staff opinion and the patients' opinion sensitivity, specificity and predictive values were calculated. RESULTS: 79 patients were included in this study. The sensitivity of the opinion of the nursing staff was 54%, the specificity 80%. The predictive values of the positive and negative test results were 59% and 76% respectively. The sensitivity of the patients' opinion was 68% and the specificity 80%. The predictive value of the positive test result was 65% and that of the negative test result 82%. CONCLUSION: Neither the opinion of the nursing staff, nor the opinion of the patients were valid methods to identify hearing-impaired nursing home patients. We recommended paying more attention to tracing hearing impairment in nursing home patients: the nursing staff should be trained and a screening audiogram should be made of all patients admitted. PMID- 8510787 TI - [Endometriosis of the rectum]. AB - Intestinal endometriosis is a diagnostic and therapeutic problem. In case the rectal wall is involved the physical signs of the endometriosis may mimic rectal carcinoma. Suspicion of the correct diagnosis can be aroused by a thorough history that will uncover the periodicity of symptoms e.g. cyclic bleeding. We present two patients with rectal endometriosis externa who were eventually treated successfully by surgery. Treatment may consist of hormonal therapy, although surgery will be necessary sooner or later in the majority of patients. PMID- 8510788 TI - [Iron deficiency, a simple diagnosis?]. PMID- 8510789 TI - A report on nursing experiences. Interview by Carol McShane. PMID- 8510790 TI - Feminism in nursing: an ethical view. PMID- 8510791 TI - Minorities in nursing: my story. PMID- 8510792 TI - Nightingales in Nebraska. PMID- 8510793 TI - Protective effect of hypothermia during ischemia in neural cell cultures. AB - Hypothermia offers protection from the effects of ischemia in small animals. We have recently shown that similar to small animals, hypothermia may also be protective in an astrocytic model of "simulated ischemia" in cell culture. This study was designed to look at the protective effects of hypothermia in cultures of cerebellar granular (glutamatergic) and cortical (GABAergic) neurons. We used LDH release into the medium as an indicator for neuron damage. Experiments were all done in sister cultures, in groups of six cultures at two temperatures (37 and 32 degrees Celsius). The duration of ischemia was three hours in cerebellar granular neuronal cell cultures and six hours in cortical neurons. LDH release was measured immediately after the insult. Hypothermia protected both granular and cortical neurons. In granular cells, LDH release was 62 +/- 18 at 32 degrees and 212 +/- 15 at 37 degrees (p = 0.02). Cortical neurons showed LDH release of 15 +/- 2 at 32 degrees and 32 +/- 2 at 37 degrees (p = 0.005). Our study suggests that similar to astrocytes, the protective effects of hypothermia are evident in neuronal cell cultures from the cerebellum and the cerebral cortex. Cell culture systems should prove useful techniques in understanding mechanisms of hypothermic protection during simulated ischemia in neurons from different sites. PMID- 8510795 TI - Effects of salsolinol on cultivated endothelial cells. AB - In view of neurotoxic properties of tetrahydroisoquinolines (TIQ's) there are open questions also in regard to the disturbance of the blood-brain barrier. Because endothelial cells are an important element of this barrier the present study was designed to assess the influence of salsolinol (a TIQ formed by condensation of dopamine and acetaldehyde) on cultivated endothelial cells by physiological, biochemical and morphological investigations. For the investigations we used aortic endothelial cells because of a variety of similarities in physiology and biochemistry to brain capillary endothelial cells. Cytotoxic effects estimated by cell counting after 72 h treatment with salsolinol (IC50 = 38 mumol/l) were possibly caused by mitochondrial damages. Already after 2 h severe ultrastructural alterations of many mitochondria could be observed. The respiration activity of the cells was always inhibited after treatment with salsolinol for some hours. The damage of the mitochondria by salsolinol was not connected with inhibition of the activity of succinate dehydrogenase and cytochrome c + c1. Nevertheless the damages of mitochondrial integrity support the hypothesis that the neurotoxic effect of salsolinol is primarily caused by damaging the endothelial cells associated with a disturbance of blood-brain barrier. PMID- 8510794 TI - Fever and feeding: differential actions of macrophage inflammatory protein-1 (MIP 1), MIP-1 alpha and MIP-1 beta on rat hypothalamus. AB - Changes in body temperature (Tb) and feeding were characterized in unrestrained rats following the micro-injection into the anterior hypothalamic preoptic area (AH/POA) of macrophage inflammatory protein-1 (MIP-1), MIP-1 alpha or MIP-1 beta. After the rats recovered from the stereotaxic implantation of a single guide tube placed in the AH/POA, either one of the MIP-1 compounds or control CSF was micro injected in a volume of 1.0 microliter into this area. Changes in body temperature (Tb) and food and water intakes were monitored throughout each experiment. When micro-injected into the AH/POA in a dose of 28 or 280 pg, doublet MIP-1 and MIP-1 beta evoked a monophasic fever which increased above baseline to a mean maximum of 2.17 +/- 0.14 degrees C and 2.1 +/- 0.24 degrees C, respectively. MIP-1 alpha micro-injected similarly evoked a biphasic fever, with the Tb declining transiently at the 30 min point > or = 0.4 degrees C lower than the congruent rises in Tb evoked by doublet MIP-1 or MIP-1 beta. The secondary rise in Tb induced by MIP-1 alpha had a latency of 1.5-2.0 hrs and reached a maximum of 1.56 +/- 0.16 degrees C. Although all three cytokines significantly attenuated the rats' mean intake of food during the 24 hr interval after their micro-injection into the AH/POA, doublet MIP-1 exerted the most potent anorexic effect in comparison to that of the saline control rats. However, neither body weight nor intake of water was altered significantly by the three cytokines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510797 TI - Nerve growth factor antibodies recognize neurotrophin-3. AB - The immunological properties of the neurotrophins NGF, BDNF, and NT-3 were compared using polyclonal and monoclonal antibodies against the beta subunit of mouse NGF. Affinity-purified anti-NGF IgG consistently recognized NGF and NT-3 on Western blots, and inhibited the trophic activity of NGF and NT-3 but not BDNF. In contrast, anti-NGF monoclonal antibodies did not block the trophic activity of either NT-3 or BDNF. These results are consistent with the greater structural overlap between NGF and NT-3 than between NGF and BDNF. PMID- 8510796 TI - Insulin-like growth factors and binding proteins in the fetal rat: alterations during maternal starvation and effects in fetal brain cell culture. AB - Maternal malnutrition adversely affects fetal body and brain growth during late gestation. We utilized a fetal brain cell culture model to examine whether alternations in circulating factors may contribute to reduce brain growth during maternal starvation; we then used specific immunoassay and western blotting techniques, and purified peptides to investigate the potential role that altered levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) may play in impaired growth during maternal nutritional restriction. Fetal, body, liver, and brain weight were reduced after 72 hr maternal starvation, and plasma from starved fetuses were less potent than fed fetal plasma in stimulating brain cell growth. Circulating levels of IGF-I were reduced in starved compared to fed fetuses, while levels of IGF-II were similar in both groups. In contrast, [125I] IGF-I binding assay demonstrated an increase in the availability of plasma IGFBPs following starvation. Western ligand blotting and densitometry indicated that levels of 32 Kd IGFBPs were 2-fold higher in starved compared to fed fetal plasma. Immunoblotting and immunoprecipitation with antiserum against rat IGFBP-1 confirmed that heightened levels of immunoreactive IGFBP-1 accounted for the increase in 32 Kd IGFBPs in starved plasma. Levels of 34 Kd BPs, representing IGFBP-2, were unaffected by starvation. Reconstitution experiments in cell culture showed that IGF-I promoted fetal brain cell growth, and that when they were supplemented with IGF-I, the growth promoting activity of starved fetal plasma was restored to fed levels. These changes were measured using MTT to assess mitochondrial reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510798 TI - Kinetic study on p-tyramine metabolism in humans using stable isotope-labeled tracers. AB - A sensitive method for the determination of p-tyramine was developed using gas chromatography-chemical ionization mass spectrometry. This method was combined with a stable isotope tracer technique to study p-tyramine metabolism in humans. [2H]5-Phenylalanine was administered orally to men (5 mg/kg) as a tracer and the amounts of [2H]4-p-tyramine excreted into urine were determined at each hour. Excretion of [2H]4-p-tyramine was maximal between 1 and 2 hours following administration, at about 15 ng/kg.h in healthy adult men. Possible application in the study of metabolic disorders in human was demonstrated. PMID- 8510799 TI - Effect of bilateral denervation of the immature rat testis on testicular gonadotropin receptors and in vitro androgen production. AB - We have studied the effect of superior spermatic nerve (SSN) section on testicular gonadotropin receptors and in vitro androgen production by immature rat testis. Bilateral testicular denervation had no effect on testicular weight, serum androgens, LH, FSH and PRL levels. Denervation resulted in a significant inhibition of hCG stimulated in vitro androgen production. A reduction in the number of testicular LH receptors was observed after SSN section, while FSH binding sites remained unchanged. These results indicate that the number of LH receptors and testicular steroidogenic response to hCG are influenced by nerves reaching the testis. PMID- 8510800 TI - Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat. AB - His-dTrp-Ala-Trp-dPhe,Lys-NH2(GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 micrograms/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self potentiating effect of chronic GH pretreatment with GHRP-6 (10 micrograms/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexamethasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptides. PMID- 8510801 TI - Prostaglandin E2 and bacterial lipopolysaccharide stimulate bioactive interleukin 1 release from rat hypothalamic explants. AB - While interleukin-1 (IL-1) is intimately involved in locally modulating the acute inflammatory response, it is also able to influence processes at remote sites, i.e., in an endocrine manner. While there is as yet little evidence that IL-1 can cross the blood-brain barrier, many effects such as fever, increased slow-wave sleep, anorexia and the modulation of neuroendocrine function suggest an action of circulating IL-1 at regulatory sites within the hypothalamus. However, there is accumulating evidence for IL-1 originating within the central nervous system (CNS), and it is currently unclear as to whether the neurally mediated manifestations of the acute inflammatory response are due to activation of central or peripheral (circulating) IL-1. In this study we have characterized the release of IL-1 from rat hypothalamic explants, and we have investigated the effects of putative modulators of IL-1 release, lipopolysaccharide (LPS) and the prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha). After 1 h of incubation, IL-1 like activity in hypothalamic supernatants ranged between 175 and 2,304 munits/mg of protein; this was substantially inhibited by the addition to the bioassay system of antibodies (1:200) against IL-1 alpha, but not against IL-1 beta. LPS and PGE2 significantly stimulated IL-1 release at 100 and 1 ng/ml respectively, whereas PGF2 alpha had no effect in the range of doses tested. It is therefore concluded that the control of hypothalamic IL-1 release may be investigated by means of acute rat hypothalamic explants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510802 TI - An autoradiographic analysis of alterations in nicotinic cholinergic receptors following 1 week of corticosterone supplementation. AB - Previous studies from our laboratory have established an interaction between central nervous system nicotinic cholinergic systems and glucocorticoid hormones. When mice are treated for 1 week with exogenous corticosterone (CORT) they become insensitive to the behavioral and physiological actions of nicotine and also have a reduction in brain alpha-bungarotoxin (BTX) receptor binding. In the present study, mice were treated with high stress levels of CORT and nicotinic receptor binding was measured using quantitative autoradiographic methods. L-[3H]-nicotine and alpha-[125I]-bungarotoxin were used to label both high- and low-affinity nicotinic sites. Chronic CORT administration reduced BTX binding in 77 of 115 (67.0%) brain regions examined. In general, forebrain regions were more sensitive to this regulation than were more posterior brain regions. Hippocampal and hypothalamic regions were particularly susceptible, with binding in treated animals being reduced by up to 80% in some nuclei. L-[3H]-nicotine sites were not as sensitive to CORT regulation as binding was significantly reduced in only 7 of the 83 (8.4%) regions measured. Regions affected were restricted to the thalamus and septum. The mechanism by which CORT reduces brain nicotinic cholinergic receptor binding is unknown and may or may not be dependent on CNS glucocorticoid receptors. PMID- 8510803 TI - Central 5-HT1A receptors inhibit adrenocortical secretion. AB - Serotonin (5-HT) is generally considered to serve a facilitatory role in the regulation of adrenocortical secretion. Numerous studies have shown that administration of 5-HT1A receptor agonists increases plasma corticosterone (CS) concentrations in rats; however, the mechanism has not been established. Rats were prepared with a cannula implanted above the lateral cerebral ventricle, or bilateral cannulae above the hypothalamic paraventricular nuclei (PVN), the site of the perikarya of corticotropin-releasing factor (CRF)-secreting neurons regulating adrenocortical secretion. In sodium pentobarbital-anesthetized rats, intracerebroventricular and intra-PVN administration of 5-HT resulted in a multi component dose-response curve in plasma CS, whereas administration of 5-HT in conscious animals resulted in low-dose inhibition and higher dose elevation of plasma CS levels. Under pentobarbital anesthesia, central administration of the selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone decreased plasma CS levels, relative to saline-treated control rats, at all doses tested (0.001-20 nmol). In conscious rats, administration of 8-OH DPAT decreased adrenocortical secretion at lower doses and significantly increased plasma CS concentrations at higher doses. Ipsapirone produced similar but less pronounced effects. In contrast, intraperitoneal injection of 8-OH-DPAT (2 mumol/kg) increased plasma CS concentrations, but this was not prevented by prior intracerebroventricular administration of the 5-HT1A antagonist, NAN-190 (5 nmol). Pentobarbital anesthesia completely blocked the plasma CS response to peripheral administration of 8-OH-DPAT. In view of the adrenocortical activating effects of hypotensive stimuli, we speculate that the well-documented hemodynamic changes following 5-HT1A receptor stimulation may be responsible for the adrenocortical responses observed. Our data demonstrate that low doses of 5-HT1A agonists delivered directly into the CNS decrease adrenocortical secretion. Since intra-PVN injections of 8-OH-DPAT to pentobarbital-anesthetized rats also decreased hypothalamo-pituitary-adrenocortical activity, it appears that a component of the inhibitory effect of 5-HT1A receptor activation is mediated by a direct effect at the level of the PVN, and presumably involves CRF-secreting neurons. PMID- 8510804 TI - Mutual synaptic associations between neurons containing neuropeptide Y and neurons containing enkephalin in the arcuate nucleus of the rat hypothalamus. AB - We determined reciprocal synaptic associations between neurons containing neuropeptide Y (NPY) and neurons containing enkephalin-8 peptide (Enk-8) in the arcuate nucleus (ARC) of the rat hypothalamus by using a double-staining immunocytochemical method. Animals treated with an intraventricular administration of colchicine and animals treated with a hemicomplete cut of the medial basal hypothalamus were used. We principally labeled NPY with silver-gold particles and Enk-8 with diaminobenzidine (DAB) chromogen but in part labeled reversely the two antigens to obtain better visualization of Enk-8 cell bodies. Neurons immunoreactive for NPY were found in the mediobasal area, while those for Enk-8 were located somewhat laterally. Their fibers, however, were densely distributed throughout the ARC in a similar fashion. Electron microscopically, we found synaptic junctions between axonal terminals of Enk-8 neurons and perikarya of NPY neurons and between axonal terminals of NPY neurons and perikarya of Enk-8 neurons. In addition, we found synaptic junctions between immunoreactive Enk-8 cell bodies and processes and also between immunoreactive NPY cell bodies and processes. These interneuronal associations may contribute to the interaction of information coming in or going out from this nucleus. PMID- 8510805 TI - Involvement of vasopressin in histamine- and stress-induced prolactin release: permissive, mediating or potentiating role? AB - Arginine vasopressin (AVP) appears to be involved in the histamine (HA)- and stress-induced prolactin (PRL) release. The present investigation was performed in male rats to clarify whether the role of AVP in HA- and restraint stress induced secretion of PRL is mediating (i.e., the effect of HA or stress is transmitted via AVP) or permissive (i.e., the presence of AVP is required to obtain a stimulatory effect of HA or stress on PRL secretion). Furthermore, we studied whether AVP possessed a potentiating effect on the HA- or stress-induced PRL release. PRL secretion was stimulated 14- to 17-fold by intracerebroventricular infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited about 80% by immunoneutralization of endogenous AVP with a specific AVP antiserum (abAVP). When specific AVP V1- or V2 receptor agonists, which were not bound by the AVP antiserum, were administered intravenously together with the AVP antiserum, the PRL response to HA or restraint stress was partly (> 50%) reestablished. This effect was observed at low (1.2 or 0.1 nmol) as well as high (3.8 or 0.4 nmol) doses of agonists and when these were administered alone or in combination. In non-immunoneutralized animals, separate administration of agonists at low or high doses as well as combined administration of agonists at low doses had no or only a minor effect on PRL secretion, while combined administration of V1- and V2-agonist in high doses stimulated PRL secretion 6-fold. Taken together, these observations indicate that AVP has a permissive role.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510806 TI - Dexamethasone potentiates serotonin-2 receptor-mediated intracellular Ca2+ mobilization in C6 glioma cells. AB - Serotonin (5-hydroxytryptamine; 5-HT) caused a transient increase in intracellular Ca2+ in C6BU-1 glioma cells in a concentration-dependent manner; half maximally at 73 nM. The 5-HT2 agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2- aminopropane also increased the levels of intracellular Ca2+, whereas the 5-HT1C agonist 1-(3-chlorophenyl)piperazine and 5-HT1A agonist 8-hydroxy-2- (di-n propylamino)tetralin were completely ineffective. Ketanserin and spiperone blocked the response to 5-HT at a nanomolar concentration, but the 5-HT3 antagonist MDL 72222 had no effect on it. Thus 5-HT2 receptors are responsible for activating Ca2+ mobilization in C6 glioma cells. Treatment of C6 glioma cells with dexamethasone potentiated the ability of 5-HT to cause intracellular Ca2+ mobilization in both a dose- and time-dependent manner. The dose-response curve for 5-HT was shifted 9-fold to the left compared to controls, and the Vmax value was also significantly enhanced. This enhanced Ca2+ mobilization was completely inhibited by ketanserin dose-dependently. In addition, the treatment with dexamethasone enhanced fluoride-activated Ca2+ mobilization, suggesting that the enhanced GTP binding protein function is one of the mechanisms responsible for the enhancement of the 5-HT response induced by dexamethasone treatment. This enhancement of agonist activity was mediated by the type II glucocorticoid receptor (GR) since RU 38486, an inhibitor of the type II GR, antagonized the dexamethasone-induced enhancement. PMID- 8510807 TI - Effects of subchronic implantation of hydrocortisone phosphate-releasing osmotic pumps on peripheral gonadotropin levels and estradiol feedback to gonadotropin secretion in the cynomolgus monkey. AB - The purpose of our study was to investigate subchronic effects of moderate hypercortisolemia on serum gonadotropin and estradiol (E2) levels in the primate using a repeated-measures experimental design. Osmotic pumps which released hydrocortisone 21-phosphate (HP) at a dose of 5 mg/day were implanted subcutaneously (s.c.) in each of five cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed hormone infusion. Subsequently, osmotic pumps which released HP at a higher dose of 15 mg/day were implanted s.c. in four of the initial five monkeys for the longer period of two menstrual cycles. The pumps were filled with saline for the two additional control cycles, one of which preceded and one of which followed HP infusion at 15 mg/day. The control cycle which followed HP infusion at 5 mg/day and the control cycle which preceded HP infusion at 15 mg/day were separated by at least one menstrual cycle. Administration of HP at the lower dose elevated serum cortisol levels 1.4-fold and decreased serum adrenal androgens to 0.6 of the pretreatment baseline. The higher dose of HP elevated serum cortisol levels 1.7-fold and suppressed serum adrenal androgens to 0.4 of the baseline. In the menstrual cycle following HP infusion serum cortisol levels were depressed to 0.8 and 0.6 of the pretreatment levels after the lower and the higher dose of HP, respectively. Serum levels of adrenal androgens returned to the baseline after the lower dose of HP, but were still suppressed to 0.5 of the baseline after the higher treatment dose. Implantation of pumps which released 5 mg/day of HP did not affect gonadotropin levels in the serum, either in the follicular phase (FP) or the luteal phase (LP) of the menstrual cycle. Serum E2 levels were increased by 77% in the FP during HP infusion at 5 mg/day (p < 0.001), but returned to control values in the LP. Implantation of pumps which released 15 mg/day of HP raised serum luteinizing hormone (LH) levels throughout the two menstrual cycles of treatment, by 111 and 96% in FPs (p < 0.001), and by 84 and 70% in LPs (p < 0.001). Conversely, serum follicle-stimulating hormone (FSH) levels were decreased by 45 and 50% in FPs (p < 0.05), and by 54 and 50% in LPs (p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510808 TI - Role of endogenous corticotropin-releasing factor in mediation of neuroendocrine and behavioral responses to cholecystokinin octapeptide sulfate ester in rats. AB - The possible involvement of endogenous corticotropin-releasing factor (CRF) in the anxiogenic and pituitary-adrenal-axis-activating effects of cholecystokinin octapeptide sulfate ester (CCK 8) was investigated in rats. Intracerebroventricularly (i.c.v.) administered CCK 8 induced an anxiogenic response in an elevated plus-maze test, and enhanced the plasma corticosterone level. Pretreatment with different dilutions (1:10, 1:20 and 1:100, i.c.v.) of CRF antiserum and different doses of a CRF receptor antagonist, alpha-helical CRF (ahCRF, 0.001-1.0 microgram, i.c.v.) prevented the anxiogenic response to CCK 8 in a dose-dependent manner. None of the doses of CRF antiserum or ahCRF alone produced any alteration in either the elevated plus-maze paradigm or corticosterone level in saline-treated control rats. The results strongly suggest that the anxiogenic and hypothalamo-pituitary-adrenal-activating effects of CCK 8 are mediated via CRF. PMID- 8510809 TI - Alterations in the postovariectomy increases in gonadotropin secretion in middle aged persistent-estrous rats: correlation with pituitary gonadotropin subunit gene expression. AB - This study compared the changes in pituitary and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at various times following ovariectomy (OVX) between young cyclic and middle-aged persistent-estrous (PE) rats and related these to the relative gene expression of the pituitary gonadotropin subunits. In intact animals, both pituitary and serum levels of LH were similar between these two age groups, while the LH beta mRNA expression was significantly (p < 0.05) greater in young rats. Following OVX in young rats, the serum LH levels markedly increased (p < 0.05) beginning on day 7 and reaching a maximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX significantly (p < 0.05) increased pituitary LH contents of young rats by day 5, but had no effect on LH contents in middle-aged females until day 30 post-OVX. These changes were associated with increases in LH beta mRNA expression in both young and middle aged females, but the levels were significantly (p < 0.05) lower in middle-aged females. Both pituitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSH beta mRNA expression was similar in both age groups. Following OVX in young rats, serum FSH levels rapidly increased (p < 0.05) on day 3 and attained tenfold higher values by day 30.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510810 TI - Beta-endorphin regulation of LHRH release at the median eminence level: immunocytochemical and physiological evidence in hens. AB - We studied the effect that beta-endorphin (beta END) might have at the median eminence (ME) on luteinizing hormone (LH)-releasing hormone (LHRH) during the ovulatory cycle of domestic hens. Thus, we assessed (a) the immunocytochemical distribution of beta END and LHRH in the hen ME, (b) the temporal changes in ME and preoptic area (POA) LHRH and beta END content, in both a spontaneous and a premature C2 ovulatory model. The premature C2 ovulation occurs 6-7 h after the administration of progesterone (P4) injected 14 h before the spontaneous second (C2) ovulation of a sequence and therefore 7-8 h earlier than expected, (c) the ME in vitro release of beta END in both models, and (d) the effect of beta END and naloxone on in vitro ME-LHRH release in the two models. In the hen, beta END cell bodies are located in the periarcuate area with axons projecting to both the ME and the POA. LHRH perikarya are located in the medial POA and anterior hypothalamus and project to the ME and infundibulum through the ventrolateral hypothalamus. In the spontaneous C2 ovulatory model, both beta END and LHRH content in the ME remained unchanged during the 14 h preceding the C2 ovulation. However, POA-LHRH content was increasing at the time of the LH surge (4 h before the expected C2 ovulation) and remained elevated until the C2 ovulation occurred. In contrast, POA-beta END content was lowest at the time of the LH surge and remained low until the C2 ovulation occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510811 TI - [Effectiveness and tolerability of simvastatin in patients with moderate-to severe hypercholesterolemia. Results of a 12-month study]. AB - Several epidemiological and clinical studies have underlined the close relationship between hypercholesterolemia and risk of coronary heart disease suggesting the opportunity of treating hypercholesterolemic patients according to their associated risk factors. Simvastatin, a drug for the treatment of hypercholesterolemia, is a competitive inhibitor of 3-Hydroxy-Methyl-Glutaryl-CoA reductase, the rate limiting enzyme in cholesterol biosynthesis. In the present study we have assessed the efficacy, safety and tolerability of simvastatin (10 20 mg) administered once daily for a period of 12 months to 50 patients with coronary heart disease (CHD) or at high risk for CHD according to the National Cholesterol Education Program. All patients underwent complete physical examination and laboratory safety tests (including blood cell count, liver function tests, creatine kinase and lipid profile) at baseline and every 6 weeks during treatment. Simvastatin was highly effective in reducing total and LDL cholesterol (-25% and -35% respectively). No significant effect on HDL cholesterol or triglycerides was obtained. Two patients were excluded after 6 weeks of treatment because of a serum creatine kinase increase (more than twice normal values). This was the only drug related side effect. In conclusion our data show that: a) simvastatin treatment is well accepted and compliance is good; b) the effect of simvastatin is evident after the first 6 weeks of treatment and is maintained during the whole treatment time; c) simvastatin is highly effective in lowering total and LDL cholesterol. When considering a patient who has had an atherosclerotic event the best deterrent to the occurrence of a subsequent event (secondary prevention) could be reduction of serum total and LDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510812 TI - [Biodegradation of dacron vascular prostheses. Physico-chemical, histological, morphometric and ultrastructural study]. AB - The paper deals with study of long-term stability as far as concerns Dacron vascular prostheses in woven and knitted double velour. Among our vascular prostheses case-reports, we evaluated three of them explanted after 11, 12, 20 years; all of the prostheses were patent. Chemical-physical, histopathological and ultrastructural analysis have been carried on in order to evaluate in vivo ageing of the examined prostheses. The results all indicate strong alterations of the original properties related to double velour of knitted prostheses and weak alterations of woven one. PMID- 8510813 TI - [Neurohormonal mechanisms in cardiac insufficiency. Possible therapeutic implications]. AB - Neurohormonal mechanisms play an important role in pathogenesis of left ventricular dysfunction. Analysis of traditional therapeutic strategies for heart failure used in the past is disappointing. Recent therapeutic strategy that aims to treat earlier patients with ventricular dysfunction with agents that counteract neurohormonal activation, seems to be more effective. However conventional drugs such as vasodilator agents, digitalis and diuretics are still useful for treatment of overt heart failure, due to their proven hemodynamic benefits. A lot of current clinical trials, in the future, can help us to solve this problem. In this issue evolving concepts of pathophysiology of chronic heart failure and how these pathophysiologic concepts lead to the rational treatment are discussed. PMID- 8510814 TI - [Objective prevention of ictus. Data informatics from a mass screening program]. AB - The main technical and functional abilities of the computer supply to the epidemiologic program Obiettivo Prevenzione Ictus are described. The aim of the program is to investigate the epidemiology of carotid occlusive disease in subjects aged 45 to 75 by following a diagnostic and therapeutic protocol, designed to discover and treat internal carotid artery stenosis. The magnitude of the population involved is 23,140 subjects. The data from the population are collected in a three level archive whose configuration makes it possible to obtain information either from within each level and from all of them. Thus, the software adopted provides specific tools for elaboration of epidemiologic data as well as for clinical management of carriers of carotid lesion and for follow-up of treated patients. PMID- 8510815 TI - [Atrial septal aneurysm and associated anomalies. Personal experience with 38 cases]. AB - We examined 38 patients discovered to be affected by an atrial septal aneurysm (ASA) during 4014 consecutive echocardiographic examinations on an adult population in an eighteen-month period. ASA is often associated with other abnormalities, mainly mitral valve prolapse (23%), followed by aortic or pulmonary regurgitation, interatrial septal defect, tricuspid valve prolapse. It has been hypothesized that ASA could be a trigger for cardiac arrhythmias or a source of emboli to various districts. However, in our population we were not able to find any patient complaining of significant ASA-related cardiac symptoms nor affected by complications such as cardiac arrhythmias or embolic phenomena. Therefore, in our opinion this entity could be defined as quite benign neither requiring pharmacological therapy nor anticoagulant prophylaxis unless such treatments are indicated by an associated pathology. PMID- 8510816 TI - Homozygous Brattleboro rats display attenuated conditioned freezing responses. AB - In the present study we examined the influence of arginine vasopressin (AVP) on conditioned freezing behavior to aversive shock treatment by comparing the responses of Brattleboro homozygous (DI) rats, Brattleboro heterozygous (HZ) rats, and Long-Evans (LE) rats. Each animal was placed in a sound-attenuated shock chamber on the training day and given a series of 3 footshocks. On the following 4 consecutive days the rats were placed in the chambers where they had received their shock and levels of spontaneous freezing were evaluated. Levels of circulating vasopressin-associated neurophysin (NP) were subsequently determined in each rat strain. For each of the 4 test days, DI rats displayed significantly less freezing behavior when compared with LE rats and HZ rats. HZ rats displayed trends towards attenuated freezing responses when compared with LE rats. The data indicate that a relationship exists between the levels of central nervous system (CNS) and circulating AVP, and the amount of freezing displayed by each strain. These preliminary results suggest that vasopressin may be involved in appropriate autonomic and emotional responses to fearful stimuli in fear conditioning paradigms. PMID- 8510817 TI - Differential expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL 6R) mRNAs in rat hypothalamus. AB - Using the sensitive technique of reverse transcription followed by polymerase chain reaction (RT-PCR), the expression of interleukin-6 (IL-6) and its receptor (IL-6R) in rat hypothalamus was investigated. Our results show a differential expression of the mRNAs for IL-6 and IL-6R during postnatal development: whereas IL-6 mRNA slightly declines with increasing age, IL-6R mRNA levels markedly increase (4-fold). The time course of these changes correlates with the maturation of the hypothalamo-pituitary-adrenocortical axis, indicating an involvement of the IL-6 system in neuroendocrine regulation. Expression of both genes in other brain areas suggest additional functions in the central nervous system (CNS). PMID- 8510819 TI - Chick retina and pineal gland differentially respond to constant light and darkness: in vivo studies on serotonin N-acetyltransferase (NAT) activity and melatonin content. AB - Oscillations in serotonin N-acetyltransferase (NAT) activity and melatonin content were investigated in retina and pineal gland of chicks kept for 5 days in constant darkness (DD) or continuous light (LL). Under DD the rhythm of the pineal melatonin biosynthesis resembled that found under diurnal illumination (LD), whereas in the retina DD resulted in significant elevations of NAT activity and melatonin level during subjective light. A low-amplitude rhythm of retinal NAT activity continued under LL with a period close to 24 h. In the pineal gland, light exposure suppressed the level of NAT activity and melatonin content (an effect being substantially weaker than that observed in retina), delayed the first peak of NAT activity by 3 h, and prolonged the rhythm's period to about 26 h. Our data suggest the existence of some differences in the activity of circadian oscillators that regulate the melatonin generating system in the retina and pineal gland of chick. PMID- 8510818 TI - Seizure activity causes a rapid increase in sulfated glycoprotein-2 messenger RNA in the adult but not the neonatal rat brain. AB - The present study investigated the changes in sulfated glycoprotein-2 (SGP-2) messenger RNA at various times following kainic acid-induced seizure onset in adult and neonatal rat brain. Double labelling using immunostaining of the astrocyte-specific glial fibrillary acidic protein indicated that SGP-2 expression was rapidly and transiently increased in granule cells of the dentate gyrus up to 8 hours after seizure onset. Thereafter, and up to 7 days following seizure onset, the majority of cells exhibiting increased SGP-2 expression were astrocytes located in the molecular layer of the dentate gyrus and in the alveus, as well as in regions adjacent to CA3 and CA1 pyramidal cells. No increase in SGP 2 mRNA was detected in pyramidal neurons selectively damaged by KA. In addition, increased expression of SGP-2 following KA administration was not observed in neonatal rat hippocampus prior to postnatal day 21. The results argue against a role for SGP-2 in KA-induced neuronal death and demonstrate a surprisingly rapid increase in astroglial gene expression following seizure activity, thus supporting a role for SGP-2 in synaptic plasticity. PMID- 8510820 TI - Branching enhancement by basic fibroblast growth factor in cut neurite of hippocampal neurons. AB - Basic fibroblast growth factor (bFGF) has strong neurotrophic effects both in vivo and in vitro on various brain neurons. bFGF enhanced the branching of laser beam-damaged axons of primary cultured hippocampal neurons with a suppression of the neurite's re-elongation. Conditioned medium prepared from astrocytes, on the contrary, prolonged the length of the cut neurite, but lacked a branching enhancement effect. Other neurotrophic factors, such as nerve growth factor and epidermal growth factor, did not affect the neurite branching or re-elongation. These results suggest that bFGF prevents neuronal death through promoting the branching of the cut neurite. PMID- 8510821 TI - Rat retinal ganglion cells express Ca(2+)-permeable non-NMDA glutamate receptors during the period of histogenetic cell death. AB - Local application of glutamate agonists to retinal ganglion cells (RGNs) was performed in retinae isolated from pigmented rats aged between 3 and 8 days postnatally. A vast majority of RGNs displayed current responses to glutamate (Glu), N-methyl-D-aspartate (NMDA), quisqualate (QA), alpha-amino-2,3-dihydro-5 methyl-3-oxo-4-isoazolepropanoic acid (AMPA), kainate (KA) and domoate (DA). In Na(+)-free extracellular solution with elevated Ca2+, non-NMDA agonists elicited large (up to 200 pA) inward currents that were completely blocked by 6,7 dinitroquinoxaline-2,3-dione (DNQX) and Cd2+. MK-801 also induced a partial block of cationic currents in Na(+)-free saline. In standard salt solutions, current voltage relationships of Glu-R-mediated currents were often inwardly rectifying in the presence of D-aminophosphonovalerat (D-APV), as is typical of Ca(2+) permeable non-NMDA receptors. The presence of inward rectification in the current voltage relationship was always associated with a high value of the cationic permeability ratio PCa2+/PCs+ (> 0.8). However, in about half of the investigated RGNs no inward rectification was observed under standard recording conditions. Our results lead to the suggestion that expression of Ca(2+)-permeable Glu receptor subunits may contribute to regulation of cell numbers in the postnatal retina. PMID- 8510822 TI - Bilateral changes of substance P-, neurokinin A-, calcitonin gene-related peptide and neuropeptide Y-like immunoreactivity in rat knee joint synovial fluid during acute monoarthritis. AB - It has been hypothesized that the nervous system contributes to the symmetrical response in rheumatoid arthritis. In order to elucidate this, the bilateral concentrations of substance P-like immunoreactivity (SP-LI), neurokinin A-LI (NKA LI), calcitonin gene-related peptide-LI (CGRP-LI) and neuropeptide Y-LI (NPY-LI) in rat synovial fluid during acute monoarthritis were studied. Equal volumes (0.05 ml) of either Freund adjuvants, carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha were injected into the right and saline into the left knee joint. Control rats were given saline bilaterally. Perfusates were obtained from both knees simultaneously at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. Increase of SP-, NKA-, CGRP- and NPY LI in synovial fluid occurred in both knees after injections with the pro inflammatory substances into the right joints as compared to controls, except for unchanged SP-LI in the right knee joint after 24 h following hrIL-1 alpha injection. There was, however, generally no significant difference in the peptide contents between the right knee (injected with pro-inflammatory substance) as compared to the left knee (given saline) at 2, 6 or 24 h after injection except at three occasions. The results show that experimentally induced monoarthritis induces bilateral changes in synovial fluid peptide content. PMID- 8510823 TI - Differential behaviour of PC12 cells grafted into rat hippocampus and striatum. AB - To investigate the mechanisms involved in graft survival, a rat cell line (PC12) that differentiates into sympathetic-like neurons by exposure to trophic factors has been grafted into rat striatum and hippocampus, two structures which differ in their amounts of trophic factors. Our results show that grafted PC12 cells behave differently depending on the area of implantation; they display a differentiated morphology in the hippocampus and proliferate as a tumor in the striatum. A qualitatively similar immunological reaction occurs in both structures, characterized by the invasion of T and B lymphocytes, macrophage-like cells and by the expression of major histocompatibility complex class I and II antigens around the graft. PMID- 8510824 TI - NMDA neurotoxicity in murine cortical cell cultures is not attenuated by hemoglobin or inhibition of nitric oxide synthesis. AB - The role of nitric oxide in N-methyl-D-aspartate (NMDA) neurotoxicity was investigated in murine cortical cell cultures. Exposure of cultures to 300 microM NMDA for 5 min resulted in death of 50-80% of neurons over the subsequent 24 h. This injury was not attenuated by hemoglobin, the nitric oxide synthase (NOS) inhibitors NG monomethyl-L-arginine (MMA) or N omega-nitro-L-arginine (NA), or L arginine depletion. Hemoglobin and NOS inhibitors consistently prevented the increase in cyclic guanosine monophosphate (cGMP) seen after NMDA exposure. These results suggest that NMDA neurotoxicity in this cell culture system is mediated, at least in part, by mechanisms other than NOS activation. PMID- 8510825 TI - Reduced diameter and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail. AB - The diameter and conduction velocity of myelinated fibers in the sciatic nerve isolated from neurofilament-deficient quail ('quiver') were compared with those from wild quail. The diameter was significantly reduced in quiver, however, the frequency distribution formed three peaks as did that observed in the wild. The fibers were categorized in three groups possessing different conduction velocity. The conduction velocity appeared to be proportional to the diameter in each strain, and was significantly reduced in quiver. These results indicate that, although the diameter and conduction velocity are reduced in quiver fiber, the correlation between the parameters observed in wild quail is still preserved. PMID- 8510826 TI - Antinociceptive effects of intrathecally administered endothelin-1 in mice. AB - Intrathecal administration of endothelin-1 (ET-1) produced dose-dependent antinociceptive effects in the tail-flick test. The antinociceptive effects of ET 1 were attenuated significantly by pretreatment with naloxone and the delta receptor-selective antagonist naltrindole. The antinociceptive effects of ET-1 were also significantly attenuated by pretreatment with verapamil, an L-type Ca(2+)-channel blocker. These results suggest that the mechanism underlying the antinociceptive effects of ET-1 involves mediation, at least in part, by Ca(2+) induced release of endogenous opioids, which act on delta-opioid receptors. PMID- 8510827 TI - Amyloid beta protein precursor accumulates in swollen neurites throughout rat brain with aging. AB - We immunocytochemically studied the expression of amyloid beta protein precursor (APP) in the brains of normal aged rats, and found APP accumulation in swollen neurites, most of which were axons. These swollen neurites appeared throughout the central nervous system of aged rats; most of them were negative for neurofilament, ubiquitin, and tau. Such widely distributed APP accumulation in swollen neurites may reflect impaired fast axonal transport due to aging. APP immunostaining may be a good method to detect widely distributed age-related changes. PMID- 8510828 TI - Distribution of calcium binding protein mRNAs in rat cerebellar cortex. AB - The distribution of three calcium binding protein mRNAs in the rat cerebellar cortex was investigated using alkaline phosphatase labelled specific antisense oligodeoxynucleotide probes. Calbindin D28k mRNA was detected in the Purkinje cells, parvalbumin mRNA was located in the Purkinje cells and also in basket/stellate cells of the molecular layer. Calretinin in contrast was found only in the granule cell layer. Use of multiple alkaline phosphatase (AP) labelled oligodeoxynucleotides resulted in an increase in signal strength and reduced detection time with no increase in background staining indicating the utility of these enzyme labelled probes for non-isotopic in situ. PMID- 8510829 TI - Low frequency of the APP 670/671 mutation in familial Alzheimer's disease in Sweden. AB - Molecular genetic studies have identified disease-causing mutations at codon 717 of the amyloid protein precursor gene in families with early-onset Alzheimer's disease. Recently, we reported a new mutation at codon 670/671 in a large Swedish family with Alzheimer's disease. The mutation results in two amino acid changes at the N-terminal of the beta-amyloid region. In the present study, we screened for the APP 670/671 mutation in sufferers from 31 other Swedish families with Alzheimer's disease using PCR and restriction enzyme digestion. The mutation was found only in the family previously reported and not in any other family. It is concluded that this mutation is a rare cause of familial Alzheimer's disease in Sweden. PMID- 8510830 TI - Preparation of an antiserum using a fusion protein produced by a cDNA for rat aromatic L-amino acid decarboxylase. AB - Aromatic L-amino acid decarboxylase (AADC) decarboxylates L-DOPA and 5 hydroxytryptophan into dopamine and serotonin, respectively. Starting from a rat AADC cDNA clone isolated in our laboratory, we produced a beta-galactosidase-AADC fusion protein in E. coli. It was purified from inclusion bodies and injected into a rabbit. The antiserum identified AADC on a Western blot of extracts from rat organs as a unique 50 kDa band; it also strongly reacted by immunohistochemistry with dopaminergic and serotonergic neurons. This new beta galactosidase-AADC fusion protein then constitutes a useful tool for producing AADC as an antigen free of contamination by mammalian proteins. PMID- 8510831 TI - Appearance of new receptive fields in rat dorsal horn neurons following noxious stimulation of skeletal muscle: a model for referral of muscle pain? AB - To test the hypothesis that painful stimuli to skeletal muscle lead to a widespread unmasking of synaptic connections in dorsal horn neurons, intramuscular injections of bradykinin (BKN) were made outside the receptive fields (RFs) of these cells in the rat. Following BKN injections, new RFs all of which were located in the deep tissues and had high mechanical thresholds appeared in 9 out of 21 (42.8%) nociceptive dorsal horn neurons which originally had a single RF in deep tissues or in the skin. The appearance of new RFs may lead to a mislocation of the source of pain if in fact the impulse activity of a nociceptive dorsal horn neuron contains information on the site of the stimulus. PMID- 8510832 TI - Evidence from the rat for a general factor that underlies cognitive performance and that relates to brain size: intelligence? AB - The data on a group of 22 rats, each measured for their speed of reasoning, accuracy of reasoning, response flexibility, and attention for novelty, were subjected to two different methods of factor analysis. By both methods, the correlation matrix of their performance was consistent with a single-factor model. In a second cohort of rats, where brain size was known, the score for this 'general factor' was computed. The regression for brain weight and the general factor was significant. PMID- 8510833 TI - Listen to your heart. PMID- 8510834 TI - When a patient refuses treatment. PMID- 8510835 TI - Reversing acute dehydration. PMID- 8510836 TI - Tuning in to ototoxicity. The inside story. PMID- 8510838 TI - The real Virginia. PMID- 8510837 TI - What you should know about women and heart disease. PMID- 8510839 TI - GI endoscopy--managing the full scope of care. PMID- 8510840 TI - Recognizing the dangers of free flow from an E.I.D. PMID- 8510841 TI - Getting through your first code. PMID- 8510842 TI - The painful promise. PMID- 8510843 TI - Complications. Pseudomembranous enterocolitis. PMID- 8510844 TI - AIDS update. What to tell patients about the female condom. PMID- 8510845 TI - Blocking i.v. drug incompatibilities. PMID- 8510846 TI - A.I.D.S. patient--code controversy. PMID- 8510847 TI - Coping with rejection. PMID- 8510848 TI - Saudi soldier, Saudi teacher. PMID- 8510849 TI - Creating a paradigm shift in benefits realization. PMID- 8510850 TI - Women's health: a powerful public issue. PMID- 8510851 TI - Charting--one national standard, one form. PMID- 8510852 TI - Patient privacy in a public institution. PMID- 8510853 TI - Quantum leap into continuous quality improvement. AB - Prior to a JCAHO accreditation visit, Southeast Georgia Regional Medical Center implemented a program for improved prevention and treatment of nosocomial pressure ulcers. Forms were developed for monitoring skin integrity and therapy beds were tried from a vendor, which also provided a computerized assessment tool. Results included 15 percent pressure ulcer prevention in addition to enhanced collaborative nursing practice. PMID- 8510854 TI - A performance-based development system. AB - Team efforts by nurse educators and nurse administrators resulted in modification of the orientation process to better accommodate part-time nurses. Use of the Performance Base Development System (PBDS) was initiated and scheduling flexibility was introduced as a "Med-Plus" program. Over 30 nurses have had acceptable assessments and became valuable members of the staff. Not all problems involving part-time nurses have been solved, but those related to documentation of performance ability have been addressed effectively. PMID- 8510855 TI - Addressing ethical boundaries among nurses. AB - Sexual intimacy is the primary boundary issue studied and reported in the literature, though it is not addressed directly in the ANA Code of Ethics. However, perhaps equally important are behaviors which may stem from nurses' meeting their own social and emotional needs through their work. Results of "Boundaries" workshops for more than 3000 nurses and other healthcare professionals are summarized. Recommendations are made, relative to both personal and professional behavior, along with a list of suggestions for nurse managers. PMID- 8510856 TI - Campaign '92: three more years! AB - Creative planning and well-executed graphics produced an upbeat approach to preparing staff for a JCAHO accreditation visit. Five humorous and highly visible strategies were used in a coordinated eight-week "campaign." Not only did the institution "pass the test" but there was a consensus among staff nurses that they had felt comfortable, confident and in control during interviews with the JCAHO surveyor. PMID- 8510857 TI - Where are career ladders going in the 90s? AB - Information from 543 hospitals and 200,000 RNs was obtained through a National Nursing Compensation Survey. Analysis of the data showed that 239 hospitals had clinical nurse ladders and many others were planning to initiate some form of ladder program soon. Although the theoretical framework, the process and the compensation packages varied, it is clear that clinical ladders are quite effective in recruitment and retention of registered nurses. PMID- 8510858 TI - Primary team nursing: the 90s model. AB - The nursing shortage of the late 80s necessitated development of an alternative to primary nursing to meet patient needs. After assessing the strengths and limitations of functional nursing, team nursing and primary nursing, a team designed a new model which incorporated the best features of the three. After a pilot period, "primary team nursing" has proven effective and feedback from nurses has been positive. PMID- 8510859 TI - Implementing and evaluating an attending nurse model. AB - The role of "Attending Nurse" responds to the need for a cost-effective role for experienced clinical nurses which provides increased autonomy and job satisfaction. Using Lewin's Theory of Change, a task force at UCLA Neuropsychiatric Hospital implemented a project in the Adolescent Developmental Disabilities Unit. Response was very positive both from nursing personnel and the multidisciplinary team, all of whom were involved in planning, implementation and evaluation. For Attending Nurses, overall job satisfaction improved, role conflict decreased and retention increased. PMID- 8510860 TI - School phobia: RN to BSN? PMID- 8510861 TI - Preventing transmission of bloodborne infections. PMID- 8510862 TI - IV therapy: a financial feasibility study. AB - Results of a feasibility study comparing peripheral catheters to midline catheters are summarized. A step-by-step process involving audit studies, cost figures, data collection, calculation parameters, and cost analysis determined the effectiveness of the new technology. PMID- 8510863 TI - Managing mediocrity. AB - The widespread mediocrity perceived by nurse managers in their staffs can be viewed from a different perspective--the present state of society in general. This may enable leaders to deal with some of the prevailing staff attitudes as indicative of "problems of workers" rather than "problems workers." Seen in this way, they become amenable to innovative approaches--especially through empowerment of workers to be "part of the solution." Personnel who continue to grow and develop often can be encouraged to internalize a vision which will eliminate mediocrity, increase job satisfaction and improve patient care. PMID- 8510864 TI - Unconvinced. PMID- 8510865 TI - When doctors prescribe. DEA numbers are not routinely required on script. PMID- 8510866 TI - Preparing host sites for generic root form implant. PMID- 8510867 TI - Hydroxylapatite-coated implants. Design considerations and clinical parameters. AB - It would appear that coated implants do have a place in therapy. However, their use will undoubtedly be enhanced by future developments. PMID- 8510868 TI - Sinus augmentation. Rationale, development, long-term results. AB - Sinus grafting is a proven procedure with predictable results. However, practitioners need to be aware of and adhere to the details that dictate the success of the procedure. PMID- 8510870 TI - Oral surgeons more likely to treat AIDS patients. PMID- 8510869 TI - Implant dentistry. Will it be the ninth recognized specialty? PMID- 8510871 TI - The renaissance of implantation. PMID- 8510872 TI - ADA's OSHA checklist. PMID- 8510873 TI - Pregnant employees in a nuclear medicine department. PMID- 8510874 TI - Immunoscintigraphy of tumours using 99Tcm-labelled monoclonal antibodies: a review. AB - 99Tcm is the optimum radionuclide for imaging in nuclear medicine due to its superior physical properties (E gamma of 140 keV and t1/2 of 6 h). Several techniques have recently been developed for labelling monoclonal antibodies with 99Tcm for immunoscintigraphy of human malignancies. These techniques primarily consist of either direct labelling of endogenous sulphydryl groups on the immunoglobulin with 99Tcm or indirect labelling through conjugation of a preformed 99Tcm-chelate. Direct methods offer the best promise for a one-step labelling kit but the 99Tcm-antibody may be unstable in vivo. This instability has been advantageous, however, in reducing blood background radioactivity and achieving sufficiently high tumour/blood ratios for clinical imaging. Over 1200 patients have been studied with 99Tcm-labelled monoclonal antibodies in the past decade. The majority of studies have been carried out in melanoma or colon cancer but other malignancies have also been investigated. The sensitivity has been variable and depended both on the size of the lesion and its location. Single photon emission computed tomographic imaging was helpful in some instances. Further study of labelling techniques and their effect on the pharmacokinetics of 99Tcm-labelled monoclonal antibodies as well as additional clinical evaluation of these agents is indicated. PMID- 8510875 TI - UK nuclear medicine survey, 1989/90. AB - A postal survey of UK nuclear medicine departments was carried out to obtain information on activity during the year 1989/90. A rise of 14% in the number of administrations of radiopharmaceuticals was found compared to 1982: a rise of 22% in imaging studies was offset by a 30% decrease in the number of nonimaging investigations. The estimated total number of administrations in the UK was 430,000. PMID- 8510876 TI - Comparison of serum thyroglobulin, 131I and 201Tl scintigraphy in the postoperative follow-up of differentiated thyroid cancer. AB - To evaluate the significance of 201Tl scintigraphy, 131I scintigraphy and serum thyroglobulin (Tg) levels in the postoperative follow-up of differentiated thyroid carcinoma, 86 patients were examined. Serum Tg was found to have the highest sensitivity (97%) as well as specificity (100%) for the detection of local tumour or metastases. Sensitivity and specificity of 131I scintigraphy after a therapeutic dose of 6100 MBq were 77 and 98%, respectively. For a diagnostic dose of 185 MBq 131I, sensitivity and specificity were 57 and 98%; for 74 MBq 201Tl these figures were 55 and 91%, respectively. The combination of serum Tg and 131I had a sensitivity of 100% and a specificity of 98% to detect the presence, although not always the localization, of persistent or recurrent tumour. 201Tl scintigraphy can provide useful additional information about the localization of local recurrences and metastases, especially in cases where serum Tg becomes positive and 131I uptake is absent. One has to bear in mind the possibility of discrepant results of 131I and 201Tl scintigraphy, in different tumour sites in one patient. There appeared to be no specific tendency for differential uptake of 131I versus 201Tl in relation to tumour type (papillary versus follicular) or localization with the possible exception of a higher preference for 131I uptake in cases of micrometastases of papillary cancer in the lungs. PMID- 8510877 TI - Bone mineral density in patients with noninsulin-dependent diabetes mellitus by dual photon absorptiometry. AB - Bone mineral density (BMD) in 38 male patients with noninsulin-dependent diabetes mellitus (NIDDM) was measured by dual photon absorptiometry (DPA) using a M & SE OsteoTech 300 scanner. The BMD of the second to fourth lumbar vertebrae was measured and the mean density was presented as g cm-2. The patients were distinguished according to the following three criteria: (1) blood sugar control was good or poor; (2) the duration of diabetes was long or short; (3) renal function was evaluated by effective renal plasma flow (ERPF) as good or poor. The results showed about half the cases of NIDDM had lower BMD. The patients with poor blood sugar control, longer disease duration and poor renal function had lower BMD. However, the difference between any two groups distinguished by the three criteria is not significant. We think that the causes of osteoporosis in patients with NIDDM may not be explained by only a single factor. PMID- 8510878 TI - Hemangiomas of the maxillofacial area. Usefulness of 99Tcm-labelled red cell scintigraphy. AB - Recent work reports the usefulness of radionuclides in the study of hepatic hemangiomas. In particular, 99Tcm-red blood cell (RBC) scintigraphy is useful to evaluate the vascularization and to plan the therapy. The aim of this paper is to confirm the usefulness of 99Tcm-RBC scans in the detection and follow-up of maxillofacial hemangiomas. Results using this technique in a selected group of patients with maxillofacial hemangiomas are reported. PMID- 8510879 TI - Skeletal scintigraphic findings in endemic skeletal fluorosis. AB - Endemic skeletal fluorosis is characterized by bone, joint and muscle pain, progressive ankylosis of various joints and crippling deformities. Whole body skeletal scintigraphy with 99Tcm-methylene diphosphonate was performed for 17 symptomatic subjects suffering from this disorder. The fluoride content of drinking water ranged from 4.1 to 12.9 mg l-1 (normal < 1 mg l-1). Urinary and serum fluoride levels were markedly elevated. Serum calcium (total and ionized), inorganic phosphorus, creatinine and albumin were essentially normal while serum alkaline phosphatase was elevated in six subjects (mean +/- S.D. 206 +/- 106; range 22-1072 IU l-1). Skeletal radiology revealed a wide spectrum of bony abnormalities. Skeletal scintigraphy revealed a picture similar to metabolic 'superscan' in all subjects, i.e. increased tracer uptake in axial and appendicular skeleton, reduced soft tissue uptake, poor or absent renal images, prominent costochondral junction and 'tie' sign in sternum. Increased uptake was present in all subjects irrespective of age, water fluoride content, serum alkaline phosphatase level and radiological abnormalities. Our findings suggest the presence of a high bone turnover state in endemic skeletal fluorosis irrespective of other variables. PMID- 8510880 TI - Dual isotope brain SPECT imaging for monitoring cognitive activation: physical considerations. AB - The physical considerations of using dual isotope brain SPECT imaging to monitor blood flow changes during cognitive activation studies were investigated. These factors included field uniformity, spatial resolution and crosstalk. Serial dual isotope single photon emission computed tomographic (SPECT) studies of a test tube phantom and an anthropomorphic brain phantom filled with 99Tcm and 123I were made over a 10 h period. The reconstructed counts in the 99Tcm and 123I windows were corrected for crosstalk and were plotted as a function of time. The plotted data from each window decreased over time with a half-life characteristic of each radionuclide. The relative difference between true 123I and 99Tcm region counts has to be of the order of 10% to be statistically significant at the P < 0.05 level. PMID- 8510881 TI - Dual isotope brain SPECT imaging for monitoring cognitive activation: initial studies in humans. AB - A dual isotope, single photon emission tomography (SPECT) technique using 99Tcm hexamethylpropyleneamine oxime (HMPAO) and 123I-iodoamphetamine (IMP) was investigated to determine its suitability for assessing regional cerebral blood flow (rCBF) changes resulting from cognitive activation. The similarity of the 123I-IMP and 99Tcm-HMPAO distributions under the same physiological conditions was first investigated by administering the two agents to human subjects (n = 8) either simultaneously or at different times but during the performance of the same task. Normalized ratio images generated from the 99Tcm and 123I data showed that the two tracers distributed similarly in the left and right cerebral hemispheres when administered under similar physiological conditions. There was, however, a significant anterior/posterior gradient that appears to be the result of partial volume effects due to small differences in spatial resolution of the two agents. In two subjects, 99Tcm-HMPAO was administered during a resting period with eyes-closed and 123I-IMP was injected later during visual checkerboard stimulation. Ratio images showed a localized increase in the occipital lobes during the visual stimulation consistent with the expected increase in rCBF. The dual isotope strategy appears promising for study of changes in rCBF due to cognitive activation. PMID- 8510882 TI - Problem solution. Matching a solution with the correct problem. PMID- 8510884 TI - Evaluation of IVD simulations to determine problem-solving practice capability. PMID- 8510883 TI - The role of telecommunications in healthcare reform. PMID- 8510885 TI - Methods for effective incorporation of IVD. PMID- 8510886 TI - The evolution of research and use of IVD in nursing. PMID- 8510887 TI - Peer review slates new plan. PMID- 8510888 TI - Astigmatism after keratoplasty suture removal. PMID- 8510889 TI - Complications of orbital implants. PMID- 8510890 TI - Sympathetic ophthalmia after Nd:YAG cyclotherapy. PMID- 8510891 TI - After we circle the wagons, which way do we shoot? PMID- 8510892 TI - Cataract development and cataract surgery in patients with juvenile rheumatoid arthritis-associated iridocyclitis. AB - PURPOSE: The authors used an aggressive stepladder, steroid-sparing, therapeutic algorithm in the care of patients with iridocyclitis associated with juvenile rheumatoid arthritis (JRA) to preserve vision, limit cataract formation, and improve probability of successful visual rehabilitation when cataract surgery became necessary. METHODS: The authors treated 60 patients with JRA-associated iridocyclitis with topical and regional corticosteroids, systemic nonsteroidal anti-inflammatory drugs, systemic steroids, and systemic immunosuppressive chemotherapy to achieve total quiescence of intraocular inflammation. Cataract surgery (phacoemulsification extracapsular cataract extraction) combined with pars plana vitrectomy was performed on those eyes with cataract sufficient to limit visual acuity to 20/200 or less, after maintenance of complete freedom from inflammation for at least 3 months. The incidence of cataract development and the visual outcome of cataract surgery were analyzed in those patients for whom a minimum follow-up of 1 year was available. RESULTS: Eventually, 10 of the 60 patients required systemic immunosuppressive chemotherapy in the stepladder therapeutic approach to achieve complete abolition of all active inflammation. Of 72 phakic eyes without cataract, significant cataract developed in 13 (18%) while under our care. The average postoperative stable visual acuity in this group was 20/40. Sixteen eyes of 12 additional patients had visually significant cataract at the time of our first evaluation of them. The average postoperative stable visual acuity in this group of patients after cataract surgery was 20/40. CONCLUSIONS: Iridocyclitis associated with JRA is an insidiously blinding disease, with 12% of individuals affected by this problem eventually blinded by the inflammatory consequences to the eye. A therapeutic philosophy of complete intolerance for active inflammation and limited tolerance for chronic steroid use may offer the most realistic hope for the next step in progress to prevent blindness in this patient population. The results of this study suggest that such a therapeutic attitude results in diminished cataract prevalence and decreased prevalence of vision-limiting retinal pathology, with resultant improved visual outcome of the cataract surgery which is eventually needed in a small proportion of the patients. PMID- 8510893 TI - Long-term visual outcome and complications associated with pars planitis. AB - PURPOSE: To identify the ocular complications and to statistically evaluate the possible association of pars planitis with multiple sclerosis (MS) in a homogeneous population of pars planitis patients. METHODS: The authors reexamined 36 patients and reviewed the records of an additional 18 patients (total: 54 patients, 108 eyes) with idiopathic pars planitis. RESULTS: The initial mean visual acuity of 20/46 (logMAR: 0.36 +/- 0.50) was not statistically different from the final mean visual acuity of 20/44 (logMAR: 0.34 +/- 0.45; P = 0.73), after a mean follow-up of 89.2 months. Complications included neovascularization with or without associated vitreous hemorrhage (7 eyes, 6.5%), moderate to severe cellophane retinopathy (7 eyes, 6.5%), chronic cystoid macular edema (CME) (9 eyes, 8.3%), visually significant cataracts (16 eyes, 14.8%), and retinal detachment (9 eyes, 8.3%). Significant lens opacification was associated with a greater risk of retinal detachment (P = 0.004). In four patients (7.4%), optic neuritis developed, and in an additional eight patients (14.8%) MS developed. Kaplan-Meier analysis of these data showed a 16.2% +/- 6.2% risk of MS solely developing in patients, and a 20.4% +/- 6.7% risk of either MS or optic neuritis developing, after 5 years of disease. The presence of periphlebitis at the time of pars planitis diagnosis increased the rate of development of these conditions (P = 0.002). Six patients (11.1%) had a family history positive for MS in a first degree relative. CONCLUSIONS: This study demonstrates the overall favorable visual prognosis in patients with pars planitis. Patients with significant cataract formation appear to be at greater risk for retinal detachment. Periphlebitis at the time of diagnosis of pars planitis increases the risk of development of optic neuritis or MS. The strong association demonstrated between pars planitis and MS in this study further supports a link between the two disease states. PMID- 8510894 TI - Long-term visual results and complications in children with aphakia. A function of cataract type. AB - PURPOSE: Previous studies of outcome in children with aphakia have approached the data by grouping patients according to features such as age at surgery, type of procedure, or some other common attribute. The purpose of this study is to identify factors predictive for visual outcome and complications in pediatric patients with cataracts. METHOD: One hundred seventy-four eyes in 118 patients underwent lensectomy and anterior vitrectomy for congenital or juvenile cataracts. All received early optical correction, occlusion therapy when necessary, and follow-up for at least 6 months. Visual outcome and complications were analyzed statistically to determine predictive factors. Features analyzed included cataract type, laterality, age at onset, follow-up, and corneal size. RESULTS: Statistical analysis showed that the most important predictor of long term visual outcome and complications is cataract type. Visual outcome differed significantly by cataract type, with best results in the lamellar and posterior lentiglobus groups. Unilateral cases had a mean acuity lower than bilateral cases. Other factors, such as age at surgery and corneal size, were less predictive but closely linked to cataract type. Complications, such as aphakic glaucoma, also were more closely linked to the type of cataract than to other variables. CONCLUSION: The results indicate that an important determinant of long term outcome and complications in aphakic children is cataract type. Other features were found to be closely correlated to cataract type and were not independently significant. PMID- 8510895 TI - Interactive videodisc and compact disc-interactive for ophthalmic basic science and continuing medical education. AB - BACKGROUND: The authors designed and implemented a complete curriculum in ophthalmic pathology using IBM- and Macintosh-based interactive videodisc (IVD) technology. They also redesigned a portion of this curriculum for a new television-based platform, compact disc-interactive (CD-I). METHODS: The following issues were addressed: curriculum design, instructional design, the assembly of illustrations and the ownership of such materials, the generation of computer-based medical art and animation, and programming. The issue of academic credit for faculty participating in this effort also was considered. RESULTS: The computer-based IVD program provides the following features: (1) rapid access to thousands of high-quality illustrations with the option of superimposing graphic labels and text directly over pictures; (2) the ability to view enlargements of photographs; (3) an online glossary to view definition of terms coupled with high quality photographs; and (4) a dynamic introduction to pathophysiology using interactive animation sequences. The authors were able to incorporate the same interactive features into the CD-I version. High-quality medical illustrations can be used effectively on the CD-I platform. CONCLUSIONS: Computer-based multimedia workstations are relatively expensive for personal use but may be useful if the equipment can be shared in a learning center or library. Compared with interactive computer-based solutions, consumer-oriented television-based technology such as CD-I is a relatively inexpensive vehicle for providing continuing medical education programs intended for use in the individual practitioner's office or home. PMID- 8510896 TI - Urban eye trauma. A one-year prospective study. AB - PURPOSE: The authors conducted a 1-year prospective study investigating the demographics, causation, and treatment of eye trauma in an urban population at one medical center. METHODS: All patients sustaining eye injuries who were evaluated by the ophthalmology service over a 1-year interval were included. A formal questionnaire was completed with demographic data and details of the injury being obtained. An ophthalmologic examination was performed on each patient, and examination findings, diagnostic tests obtained, diagnosis, and treatment were recorded and analyzed. RESULTS: This study included 584 eye injuries. Three hundred seventy-one injuries (70%) occurred in males and 159 (30%) in females. The average age was 30.5 years; 110 (21%) patients were pediatric. Sixty-two percent of all patients presented within 24 hours of their injury. Thirty-seven percent of all injuries occurred in the street, 31% at home, and only 13% at the workplace. For those older than 65 years of age, 48% of injuries were the result of a fall. Sixty percent of all eye injuries were caused by blunt trauma. Only 42 (8%) patients wore eye wear at the time of their injury. Diagnoses and management were recorded. CONCLUSIONS: The inner city population is more likely to sustain eye trauma as the result of an assault and is less likely to be involved in a work- or sports-related injury. Given poor compliance with outpatient management and follow-up, aggressive primary management may be indicated to optimize visual outcome. PMID- 8510897 TI - Ocular fundus findings in Malawian children with cerebral malaria. AB - BACKGROUND: Cerebral malaria is a major cause of mortality and morbidity in children in tropical regions. The pathogenesis of this important complication of Plasmodium falciparum infection is not well understood. A number of observers have commented on the presence of retinal pathology in various types of malaria. Previous reports have not demonstrated that fundus findings are significantly associated with outcome. METHODS: The authors examined the ocular fundi, by direct and indirect ophthalmoscopy, of 56 children admitted consecutively with cerebral malaria. RESULTS: Every child with a normal fundus on admission recovered fully, but two conditions were found to be associated with a poor outcome. Patients with papilledema had a relative risk of poor outcome 5.2 times greater than those without this finding (P < 0.01). Patients with retinal edema outside the posterior vascular arcades had a relative risk of poor outcome 3.9 times greater than those without this finding (P < 0.01). These two fundus findings were independently predictive of a poor outcome. CONCLUSION: Fundus findings are useful as predictors of outcome in children with cerebral malaria. The authors' findings suggest that there may be two distinct mechanisms associated with poor outcome in these children. PMID- 8510898 TI - The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. AB - PURPOSE: To investigate the relationship between microalbuminuria and the presence and severity of diabetic retinopathy in a large population-based cohort of individuals with diabetes. METHODS: Microalbuminuria was measured by an agglutination inhibition assay in random urine samples obtained from participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (n = 1139) who did not have hematuria, gross proteinuria, or a history of renal disease. Retinopathy was determined from stereoscopic color fundus photographs graded according to a modification of the Airlie House Classification System. RESULTS: Younger-onset (diagnosed with diabetes before 30 years of age) and older-onset (diagnosed with diabetes when 30 years of age or older) individuals with microalbuminuria were more likely to have retinopathy than those without microalbuminuria. Younger onset individuals who had microalbuminuria at the time of examination were more likely to have proliferative retinopathy than younger-onset subjects with normoalbuminuria. These relationships remained after controlling for glycemia, hypertension, duration of diabetes, and other potential confounders. CONCLUSIONS: Microalbuminuria is associated cross-sectionally with the presence of retinopathy in persons with diabetes and with the presence of proliferative disease in younger-onset individuals. These data suggest that microalbuminuria may be a marker for the risk of proliferative retinopathy developing. If longitudinal studies confirm these findings, individuals with insulin-dependent diabetes mellitus (IDDM) who have microalbuminuria may benefit from ophthalmologic follow up. PMID- 8510899 TI - The effect of pars plana vitrectomy and transforming growth factor-beta 2 without epiretinal membrane peeling on full-thickness macular holes. AB - PURPOSE: Surgical techniques for the treatment of macular holes generally include removal of the overlying cortical vitreous and/or epiretinal membranes. The authors demonstrate that by using vitrectomy, posterior hyaloid removal, fluid gas exchange, and transforming growth factor-beta 2 (TGF-beta 2), a growth factor that modulates the wound healing process, epiretinal membrane peeling can be avoided and the surgical procedure thereby simplified without compromising results. METHODS: A total of 24 eyes of 24 patients with stage 2, 3, or 4 full thickness macular holes were treated. Of 24 patients, 1 was lost to follow-up after suffering a stroke; the remaining 23 (17 females and 6 males) (age range, 11-81 years; mean, 64 years) were followed for 5 to 16 months (mean, 12 months). Preoperative best-corrected visual acuity ranged from 20/50 to 20/400 (mean, 20/125). A standardized vitrectomy was performed with posterior hyaloid removal and, after a near-complete fluid-air exchange, 0.1 ml of a solution containing 1330 ng of TGF-beta 2 was instilled over the macular hole. No attempts were made to peel epiretinal membranes or drain fluid from the macular hole. RESULTS: Of 23 eyes, 22 (96%) had resolution of the surrounding subretinal fluid and flattening of the macular hole (1 patient required a second procedure, in which visual improvement of 20/30 was achieved); 11 (48%) had visual acuities of 20/40 or better, 19 (85%) had visual acuities of 20/60 or better, and 19 (85%) showed an improvement in visual acuity of at least two lines (mean, 3.8 lines). The authors saw no retinal pigment epithelial mottling. CONCLUSION: The authors' results demonstrate that treatment of macular holes using vitrectomy, fluid-gas exchange, and the instillation of a solution containing TGF-beta 2, without epiretinal membrane peeling, maintains efficacy while simplifying surgery. PMID- 8510900 TI - A two-year experience with excimer laser photorefractive keratectomy for myopia. AB - PURPOSE: This report summarizes the authors' 2-year experience with excimer laser photorefractive keratectomy (PRK) on 160 eyes of 128 patients. METHODS: All eyes were treated with an excimer laser: fluence, 160 mJ/cm2; frequency, 5 Hz; ablation zone diameter, 5.0 to 5.5 mm; and depth per pulse, 0.21 to 0.27 microns. A suction fixation ring was used in all eyes either with nitrogen flow (79 eyes) or without nitrogen flow (81 eyes) across the cornea. Follow-up ranged from 1 month (152 eyes) to 24 months (12 eyes). RESULTS: At 3 months, 82% (139) of eyes achieved an uncorrected visual acuity of 20/40 or better; 83% were corrected to within +/- 1 diopter (D) of intended correction and 30% lost one line of best corrected visual acuity. At 6 months, 88% (124) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 15% lost one line of best-corrected visual acuity. At 12 months, 91% (71) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 17% lost one line of best-corrected visual acuity. At 24 months, 100% (12) of eyes achieved an uncorrected visual acuity of 20/40 or better; 91.6% were within +/- 1 D of intended correction and 0% lost one line of best-corrected visual acuity. CONCLUSIONS: In eyes with a follow-up of 6 to 24 months, 77% to 100% achieved an uncorrected visual acuity of 20/40 or better and 84% to 92% were corrected to within +/- 1 D of the intended correction. The authors conclude that excimer laser PRK appears to be a safe procedure capable of correcting the eyes of patients with low to moderate myopia with approximately the same degree of accuracy as radial keratotomy. PMID- 8510901 TI - Eyelid imbrication. An unrecognized cause of chronic ocular irritation. AB - BACKGROUND: Eighteen patients with chronic ocular irritation were examined over a 3-year period. All patients demonstrated papillary conjunctivitis and, occasionally, tarsal ulcers. Six also had floppy eyelid syndrome. Underlying every patient's symptoms was the overriding or imbrication of a lax upper eyelid on an often equally lax lower eyelid, allowing lower eyelid lashes to chronically rub the upper eyelid tarsal conjunctiva. METHODS: Chronic ocular irritation in five patients was managed with ocular lubricants. Two of these patients had floppy eyelid syndrome and required nightime shielding for nocturnal eyelid eversion. Thirteen patients underwent eyelid surgery to correct the overriding upper eyelid. Surgical procedures included full-thickness upper eyelid wedge resection, lateral canthal tendon plication, and lower eyelid horizontal shortening, using a tarsal strip procedure. RESULTS: Follow-up averaged 2.5 years. Symptomatology was adequately controlled in all patients. In addition to the five patients who received medical treatment for their symptoms, two with complicated ocular problems required continued ocular lubrication after surgery. Seven patients were successfully treated with eyelid shortening procedures and lateral canthal tendon plication. The remaining six patients underwent a variety of additional eyelid surgeries. All patients undergoing surgery had complete resolution of eyelid imbrication. CONCLUSIONS: Eyelid imbrication is a previously unrecognized cause of chronic ocular irritation. In this condition, eyelid laxity causes the upper eyelid to override the lower eyelid, allowing the lower eyelid to chronically rub and chafe the upper eyelid tarsal conjunctiva. In some cases, symptoms can be managed medically. More often, surgical intervention is required to correct eyelid laxity and prevent overriding of the upper eyelid. PMID- 8510902 TI - Prolongation of corneal allograft survival with liposome-encapsulated cyclosporine in the rat eye. AB - PURPOSE: To study the effects of different formulations of topical cyclosporine (Cyclosporin A [CsA]) on corneal allograft rejection in a rat model. METHODS: Female Lewis rats received penetrating keratoplasties from female Wistar-Furth donors. A total of 78 allogeneic grafts were performed. An additional 15 syngeneic grafts (Lewis) were used as technical controls. Two CsA preparations with equivalent drug concentrations (2.1 mg/ml) were applied as drops: CsA encapsulated in large unilamellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). Allogeneic grafts were randomly assigned to receive CsA-LIP or CsA DR beginning on the day of surgery five times daily for 10 days. Animals without any treatment or receiving empty liposomes (EM-LIP) were used as treatment controls. Grafts were graded three times weekly and a rejection index was generated based on graft clarity, neovascularization, and vessel size. RESULTS: All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 days, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or EM LIP treatment groups. The mean survival time of rejected grafts in animals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a significant difference in the mean survival time between the CsA-LIP treatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P < or = 0.05). The Kaplan Meier survival curve of the CsA-LIP treatment group was significantly different from the other experimental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR group, and 36% in the EM-LIP group. CONCLUSION: Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection. PMID- 8510903 TI - Molteno tube implantation for neovascular glaucoma. Long-term results and factors influencing the outcome. AB - BACKGROUND: The Molteno implant has been shown to be useful in the treatment of neovascular glaucoma. However, a wide range of success rates has been reported. This is related to the use of differing criteria for success, varying periods of follow-up, and difficulty in quantifying the preoperative condition of the eye. METHODS: The authors studied the long-term results of the Molteno single-plate implant in 60 eyes with neovascular glaucoma using Kaplan-Meier life-table analysis. Age, visual acuity, underlying retinal diseases, and preoperative retinal ablation treatment were evaluated to establish factors influencing the surgical outcome. The criteria for success included a postoperative intraocular pressure (IOP) of less than or equal to 21 mmHg and maintenance of vision. RESULTS: The success rate was 62.1% at 1 year, 52.9% at 2 years, 43.1% at 3 years, 30.8% at 4 years, and 10.3% at 5 years. The main causes for failure were loss of light perception in 48% of eyes (29/60), progression to phthisis bulbi in 18% (11/60), and encapsulation of the filtering bleb in 10% (6/60). The long-term surgical outcome was significantly better in patients older than 55 years of age (P = 0.048) and in those with a preoperative visual acuity equal to or better than 6/60 (P = 0.019). Eyes with neovascular glaucoma secondary to diabetic retinopathy had a better prognosis than those with a central retinal vein occlusion (P = 0.003). CONCLUSION: Although the IOP can be significantly reduced after Molteno implantation, this study suggests that in severely compromised eyes with neovascular glaucoma the main advantage of Molteno implantation is pain relief and avoidance of enucleation. PMID- 8510904 TI - Trabeculectomy and Molteno implantation for glaucomas associated with uveitis. AB - PURPOSE: This study compares the outcomes of trabeculectomy and Molteno implantation in the treatment of glaucomas associated with uveitis. METHODS: Forty-five patients with uveitis, who had undergone filtering surgery for glaucomas associated with uveitis, were reviewed retrospectively. Successful outcome was defined as final intraocular pressure (IOP) of 6 to 21 mmHg, with a minimum follow-up of 6 months without visually devastating complications or loss of light perception. RESULTS: One- and two-year life-table success rates, respectively, were 81% and 73% with trabeculectomy (16 patients); 53% and 31% with combined trabeculectomy and first-stage (reserve) Molteno implantation (19 patients); and 79% and 79% with one-stage Molteno implantation (10 patients). In 11 patients who underwent second-stage Molteno implantation after trabeculectomy failure, 1- and 2-year life-table success rates were 79% and 79%, respectively. Complications included surgically treated choroidal effusions (1/45; 2%), choroidal hemorrhages (3/45; 7%), and chronic hypotony (3/45; 7%). Follow-up in all groups ranged from 5 to 70 months (mean +/- standard deviation, 28 +/- 17 months). CONCLUSIONS: Trabeculectomy provides surprisingly good results in glaucomas associated with uveitis (modulation of wound healing with antimetabolites probably would afford an even higher success rate). However, when significant, immediate postoperative and/or moderate chronic postoperative inflammation is likely, aqueous drainage devices appear more likely to control IOP. PMID- 8510905 TI - Argon laser trabeculoplasty in pigmentary glaucoma. AB - PURPOSE: To evaluate the long-term effect of argon laser trabeculoplasty (ALT) in pigmentary glaucoma. METHODS: The authors retrospectively analyzed results of ALT in 32 eyes of 32 patients with medically uncontrolled pigmentary glaucoma. Data were longitudinally adjusted to normalize the disparity in time of follow-up and evaluated by life-table analysis. RESULTS: Mean age (+/- standard deviation) was 45.1 +/- 13.1 years (range, 23-72 years) (males, 46.3 +/- 13.7 years; females, 42.9 +/- 12.2 years). Mean baseline intraocular pressure (IOP) was 27.8 +/- 5.3 mmHg. Mean follow-up time was 33.0 +/- 5.0 months (range, 1 week [immediate failures] to 96 months). Three eyes were lost to follow-up at 3 months. Eleven eyes required trabeculectomy between 1 week (2 eyes) and 37 months after laser treatment. Life-table analysis indicated a cumulative success for all eyes of 80% at 1 year, 62% at 2 years, and 45% at 6 years. Mean IOP was significantly reduced (P < 0.001; paired Student's t test) for male and female eyes at all intervals calculated. Age was a significant factor in determining time to failure. CONCLUSION: Argon laser trabeculoplasty is effective in pigmentary glaucoma. Younger patients had a greater chance of success than older patients at all intervals. This became highly significant (P < 0.001) after 3 years. PMID- 8510906 TI - Early clinical experience with the Baerveldt 350-mm2 glaucoma implant and associated extraocular muscle imbalance. AB - PURPOSE: The Baerveldt glaucoma implant is a new commercially available aqueous drainage device. Clinical data on the performance of the implant are relatively limited. The purpose of this investigation is to explore potential advantages and disadvantages of this implant over the more widely used Molteno implant. METHODS: Retrospective analysis was performed on 37 eyes of 36 patients with refractory glaucoma who underwent placement of a mid-sized Baerveldt 350-mm2 implant. Patient selection was based on previous failure of conventional medical, laser, and surgical management, with poor prognosis for further glaucoma surgery and adjunctive antifibrosis therapy. RESULTS: Significant postoperative extraocular motility restriction and heterotropia were found in the operated eyes. Twenty three (77%) of 30 eyes measured have significant heterotropia in primary gaze and restriction of gaze into the quadrant of the implant. As a result, 11 (65%) of 17 functionally binocular patients have diplopia in primary gaze. CONCLUSIONS: Pending further study, the authors are avoiding placement of the Baerveldt 350 mm2 implant in both binocular and monocular patients due to the high frequency of induced heterotropia and motility restriction. PMID- 8510907 TI - Echographic evaluation of glaucoma shunts. AB - BACKGROUND: It is frequently impossible to determine by clinical examination alone if a filtering bleb is present over the equatorial plate(s) of a glaucoma shunt. This uncertainty can result in management dilemmas when patients with these devices have elevated intraocular pressures (IOPs). The authors describe how standardized echography can be used to determine if fluid is present around the plates and to characterize the blebs. METHODS: Four hundred twenty-seven plates in 269 patients who had undergone single- or double-plate Molteno implantation underwent standardized echography (both A- and B-scan examinations) to determine if blebs were present around the plates, primarily when results of slit-lamp examinations had been inconclusive. Bleb sizes, locations, and characteristics also were evaluated. RESULTS: Sixty-five percent of the plates had associated blebs, which were graded according to their sizes (small, medium, and large, in 29%, 44%, and 27% of plates with blebs, respectively). Fluid (which appeared as an echolucent area) could be seen underlying and/or overlying the plates (which appeared as echodense lines). Larger blebs were often associated with scleral flattening. Although bleb sizes did not necessarily correlate with the levels of IOP control, the presence of a bleb on ultrasound was indicative of tube patency. CONCLUSION: Standardized echography was invaluable in the postoperative management of patients who had undergone Molteno implantation because it demonstrated the presence or absence of blebs and characterized them when results of slit-lamp examinations had been inconclusive. This technique also can be used to evaluate similarly designed aqueous shunting devices. PMID- 8510908 TI - Young patient trabeculectomy. Assessment of risk factors for failure. AB - BACKGROUND: Various risk factors for failure of glaucoma filtering surgery, including young age, have been suggested. METHODS: A retrospective study of 113 trabeculectomies in 113 patients, ranging in age between 11 and 49 years (mean, 33.3 +/- 10.5 years), was carried out to determine the influence of these risk factors in young patients. RESULTS: A successful outcome (intraocular pressure [IOP] < or = 21 mmHg without antiglaucoma treatment), assessed by life-table analysis, was achieved in 54% of trabeculectomies after 38 months (mean follow up, 36.7 +/- 29.7 months). Previous ocular surgery (e.g., glaucoma filtering, cataract, or conjunctival surgery) and previous laser therapy (i.e., argon laser trabeculoplasty and YAG laser iridotomy) both significantly reduced the success rate. An IOP greater than 40 mmHg during the course of the disease was found to adversely affect the outcome. No direct correlation between success rate and age and no racial difference were demonstrated. Success rates for specific diagnoses were not significantly different. Postoperative subconjunctival injections of 5 fluorouracil (5-FU) did not significantly improve the success rate. A Cox regression analysis of various prognostic variables identified previous cataract surgery (hazard ratio, 4.4), argon laser trabeculoplasty (hazard ratio, 3.4), previous glaucoma filtering surgery (hazard ratio, 2.5), nonfiltering glaucoma surgery (hazard ratio, 2.2) and IOP greater than 40 mmHg (hazard ratio, 2.4) to be the major risk factors for glaucoma filtering surgery failure. CONCLUSION: A majority (74%) of the patients in our series had at least one of these risk factors, thus explaining why young patients, in general, have lower success rates for trabeculectomy. PMID- 8510909 TI - Individual variability in the diurnal intraocular pressure curve. AB - BACKGROUND: Reduction of intraocular pressure (IOP) is a primary goal of most glaucoma treatments. However, because the IOP varies during the day, single measurements performed in an ophthalmologist's office do not necessarily provide information on the peak level and fluctuation of the IOP. METHODS: Home tonometry was performed to gain more information on the nature of the diurnal IOP curves and on their variability. One hundred seventy-six patients with open-angle glaucoma (OAG), 55 subjects with ocular hypertension (OHT), and 18 control individuals measured their IOP five times daily at home for 4 to 8 consecutive days using a self-tonometer. RESULTS: Well-defined diurnal IOP variations were observed in all three groups with a predominance of curves with morning or mid day maxima. Erratic IOP curves without a diurnal rhythm were present in OHT (22%) and OAG (16%) patients but not in control subjects. Differences between the curves of the two eyes of an individual were frequent in OHT (33%) and OAG (36%) patients but not in control subjects (6%). Finally, the majority of OHT (72%) and OAG (66%) patients showed a difference in their diurnal curve patterns on repeat home tonometry performed months apart. CONCLUSION: The authors indicate that it is difficult to rely on one eye as a control for the other. They also indicate that changes in IOP observed in the office at different visits often may be due to a shift in the type of diurnal curve rather than to a true change in the mean IOP. Monitoring of the diurnal IOP may be necessary in some cases if the clinician relies, even partially, on the level of IOP when making a decision on patient management. PMID- 8510910 TI - Effect of severing the check ligaments and intermuscular membranes on medial rectus recessions in infantile esotropia. AB - BACKGROUND: The effect of severing the check ligaments and intermuscular membranes on the dose-response curve for medial rectus recessions in patients with infantile esotropia has not been previously studied by randomized assignment techniques using contemporary control and experimental groups and masked precautions. METHODS: A prospective study of 101 patients was performed over an 8 year period. Patients were randomly assigned to either augmented or nonaugmented groups. In the former group, the medial check ligaments and intermuscular membranes were severed; in the latter group, no surgery was performed on the medial check ligaments or intermuscular membranes. Patients were postoperatively evaluated by an observer masked to group assignment. RESULTS: No difference in response to surgery was observed between the two groups at the time of evaluation, which took place, on average, 6 to 7 months after surgery. CONCLUSION: Severing the check ligaments and intermuscular membranes on patients with infantile esotropia undergoing medial rectus recessions does not appear to affect the dose-response curve. PMID- 8510911 TI - Evaluation of FASTPAC, a new strategy for threshold estimation with the Humphrey Field Analyzer, in a glaucomatous population. AB - PURPOSE: A new fast strategy for the estimation of threshold, FASTPAC, has been introduced for the Humphrey Field Analyzer. The aim of this study is to evaluate the performance, in a glaucomatous population, of FASTPAC compared with the standard full-threshold 4-2-decibel (dB) double-staircase strategy. METHODS: The sample consisted of 30 glaucoma patients experienced in automated perimetry, ranging in age from 26 to 84 years. One eye of each patient was examined with both strategies using program 24-2, target size III. The order of strategy was randomized for each patient. The results were analyzed using analysis of covariance for a two-period crossover trial. Mean deviation, pattern standard deviation, short-term fluctuation, corrected pattern standard deviation, number of stimulus presentations, and examination time were analyzed separately; test sequence and severity of field loss were considered as between subject factors and age as a covariate. RESULTS: The FASTPAC algorithm demonstrated a 36% saving in examination time (P < 0.001), a lower mean deviation (0.91 dB) (P < 0.001), and a greater short-term fluctuation (0.64 dB) (P = 0.008). The differences in mean deviation (P = 0.015) and short-term fluctuation (P = 0.033) became greater with an increase in age. As the severity of the field loss increased, the short term fluctuation increased (P = 0.043), and examination time was increased for the FASTPAC strategy, while it became shorter for the standard full-threshold strategy (P = 0.033). CONCLUSIONS: The FASTPAC strategy reduced the examination time but exhibited a decreased estimate of field severity and a greater intra test variance. PMID- 8510912 TI - Uveal involvement in systemic angiotropic large cell lymphoma. Microscopic and immunohistochemical studies. AB - BACKGROUND: Angiotropic large cell lymphoma is a rare, generally fatal disease characterized by multifocal proliferation of neoplastic mononuclear cells within the lumens of blood vessels. METHODS: The authors report the clinical and immunohistochemical features of four patients with angiotropic large cell lymphoma. RESULTS: All patients presented with central nervous system symptoms, and three of the four had fever of unknown origin and anemia. The diagnosis was established by postmortem examination of the eyes in four patients and additionally by autopsy in three of the four patients. Two of the three autopsied patients had rare foci of extravascular involvement. One patient had erythrophagocytosis. Immunohistochemical stains on paraffin-embedded sections confirmed the diagnosis of lymphoma in all four patients. CONCLUSION: The results of this study support the B-cell lymphocyte origin of angiotropic large cell lymphoma. PMID- 8510913 TI - Immunoblastic B-cell malignant lymphoma involving the orbit and maxillary sinus in a patient with acquired immune deficiency syndrome. AB - BACKGROUND: A 44-year-old man was diagnosed with acquired immune deficiency syndrome (AIDS)-related complex in 1986. Four years later, erythema and swelling of the right lower eyelid and face and a palpable mass along the right inferior orbital rim developed. Computed tomographic scans of the orbits disclosed a mass involving the right superior antrum and inferior orbit. Histopathologic examination and immunohistochemical studies of the tumor were performed. METHODS: Immunohistochemical studies were performed on paraffin sections of the neoplasm. Markers used included leukocyte-common antigen and L26 (pan B-cell marker), and MT1, Leu22, polyclonal CD3, UCHL-1, and OPD4 (pan T-cell markers). Additional markers included cytokeratin, HMB-45, lysozyme, S-100 protein, kappa, and lambda. FINDINGS: The neoplastic cells were strongly to moderately positive with LCA, L26, MT1, and Leu22. Negative staining was observed with the remaining nine antibodies. CONCLUSION: Orbital lymphomas in patients with AIDS have been rarely documented; those few reported cases showed a B-cell phenotype. The authors report an immunoblastic B cell with immunophenotypic coexpression of T-cell markers. PMID- 8510915 TI - [Cost effectiveness in nursing]. PMID- 8510914 TI - [Austrian charter for patient rights: prevent conflict--enhance understanding]. PMID- 8510916 TI - [Legally sworn nursing expert. 2 years ago, by chance, I stumbled upon the expert, and I asked myself who was an expert on nursing]. PMID- 8510917 TI - [Emancipation--a 20th century catchword?]. PMID- 8510918 TI - A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. AB - The chromosome 11p13 Wilms' tumor locus (wt1) encodes a zinc finger-containing transcription factor (WT1). WT1 binds to the consensus sequence (5'-GCGGGGGCG-3') and represses transcription when bound to this site in vivo. The mechanism of repression is not yet defined. To investigate the mechanisms of transcriptional repression and map the domains of WT1 responsible, we constructed hybrid proteins between the yeast GAL4 1-147 DNA binding domain and WT1. Fusion of a 298 amino acid glutamine-proline-rich N-terminal segment of WT1 to the GAL4 DNA binding domain created a potent transcriptional repressor. The use of N- and C-terminal truncations of this segment demonstrated that as few as 96 amino acids were required for active repression by GAL4-WT1 hybrid proteins in NIH3T3 fibroblasts. However, the truncated GAL4-WT1 fusion proteins functioned poorly as repressors in embryonic kidney-derived 293 cells, suggesting cell type-specific requirements for transcriptional repression. Site-directed mutagenesis of the WT1 repression domain revealed that deletion of homopolymeric proline and glycine regions, as well as single amino acid changes, partially inactivated the repression function. Single repressor binding sites placed upstream of the transcription start site conferred WT1-mediated repression to a heterologous promoter, whereas multiple sites resulted in additive (non-synergistic) increases in transcriptional repression. Significant repression of transcription was observed when binding sites were placed 760 base pairs upstream or 1000 base pairs downstream relative to the site of transcription initiation. We conclude that the transcriptional repression function of WT1 is contained in the N-terminal, non-DNA binding domain of the protein and that repression can be functionally transferred to a heterologous DNA binding domain. PMID- 8510920 TI - Accumulated helix-destabilizing mutations in the leucine zipper of c-Fos leads to attenuation and temperature sensitivity of function. AB - Fos protein heterodimerizes through one surface of an alpha-helical domain called the leucine zipper. We have investigated the effect of destabilizing this domain by multiply substituting small residues of its non-interacting surface with glycine. Ternary complex formation between mutated Fos, Jun and DNA was determined in vitro in the presence of denaturant. We also tested the ability of constitutively expressed, mutated Fos proteins to support anchorage independent growth of the cell line Rat1A. Combinations of two substitutions are tolerated in both assays of Fos function, while four substitutions resulted in attenuation in both functions. Rat1A expressing one of the quadruple mutants also showed temperature sensitivity in anchorage independent growth. In dense monolayers of these cells, stromelysin (a Fos-responsive gene product) decreased in abundance as a function of temperature and was less abundant even at 34 degrees C than in cells that overexpressed the wild-type c-fos mRNA. However the mutant transgene itself appeared to show temperature sensitive expression. We suggest that creating a range of glycine substitutions for small residues in the non interacting face of a leucine zipper might be of general use as a strategy to produce attenuated mutants of other transcription factors. PMID- 8510919 TI - Method of identifying inhibitors of oncogenic transformation: selective inhibition of cell growth in serum-free medium. AB - We developed a new method for evaluating inhibitors of oncogenic signal transduction pathways based on different growth abilities between normal and transformed cells in a defined serum-free medium. The growth rates of src, abl or ras oncogene-transformed cells, activated raf proto-oncogene transformed cells, and normal NIH-3T3 cells were 60-90%, 20-30% and 10% in a serum-free medium, respectively, compared to the growth rates in a serum-containing medium. An addition of a growth factor (PDGF, FGF or TGF-beta) stimulated the growth of normal NIH3T3 cells by 40-80% in a serum-free medium. Herbimycin A, a specific cytoplasmic protein tyrosine kinase inhibitor, selectively inhibited the growth of src or abl transformed cells in the serum-free medium resulting in about 10 fold or fivefold lower IC50 than those in the serum-containing medium. The antibiotic did not show such an effect on ras transformed cells, and the treatment of src transformed cells with other protein kinase inhibitors or cytotoxic drugs showed little IC50 shifts between the two media. Thus, this method of comparing growth inhibition in the serum-free and the serum-containing media may be useful in evaluating specific inhibitors of signaling pathways mediated by growth factors and certain oncogene products. PMID- 8510921 TI - Characterization of the DNA binding and transcriptional activation domains of the erg protein. AB - erg, an ets related gene encodes a sequence specific DNA binding transcriptional activator protein. We have identified four functional domains of erg protein that are responsible for DNA binding, transcriptional activation and negative regulation of transcriptional activation. Deletion analysis revealed that the 3' ets domain of the erg protein is sufficient for DNA binding activity. Analysis of these deletion mutants also revealed the presence of two autonomous transcriptional activation domains, one at the amino and the other at the carboxyterminal region. This aminoterminal transcriptional activator domain (5' ets domain) is conserved in six of the ets genes suggesting that it (ETA, ets Transcriptional Activation domain) may contribute to a common function among these genes. The transcriptional activation function of the carboxy terminal transcriptional activation domain (CTA) was inhibited by the presence of a Negative Regulatory Transcriptional activation domain (NRT), which is located at the amino terminal region of erg DNA binding domain. These results may help in understanding the structure/function relationship of other erg/ets related proteins. PMID- 8510922 TI - Single point mutations in the SH2 domain impair the transforming potential of vav and fail to activate proto-vav. AB - The importance of an intact Src Homology 2 (SH2) domain for transformation by members of the tyrosine kinase family, including v-src, c-src, c-abl, fps and fyn is well documented. To determine the role of the SH2 domain in transformation by a protein which is not a member of this family, we employed site directed mutagenesis to change four highly conserved residues in the SH2 domain of the vav oncogene and the vav proto-oncogene (proto-vav). Proto-vav encodes a protein that contains one SH2 domain and two Src Homology 3 (SH3) domains, in addition to a number of other motifs usually found in transcriptional factors and guanine nucleotide exchange factors. Substitution of arginine 629 to glycine (R629G) and arginine 647 to leucine (R647L) in vav did not impair its transforming potential in NIH3T3 fibroblasts. By contrast, substitutions of tryptophan 622 to arginine (W622R) and glycine 642 to valine (G642V) in the vavSH2, greatly reduced its transforming potential. Similar point mutations introduced in the SH2 domain of proto-vav did not activate the transforming potential of the normal gene. Interestingly, although all the vav SH2 mutant proteins were constitutively phosphorylated on tyrosine when expressed in NIH3T3 cells, they fail to bind to a phosphorylated epidermal growth factor receptor (EGFR), regardless of their transforming potential. PMID- 8510923 TI - Increased cyclin A and decreased cyclin D levels in adenovirus 5 E1A-transformed rodent cell lines. AB - Adenovirus-(Ad)- E1A proteins carry two conserved domains (CR1 and CR2) required for transformation of primary rodent cells and essential for association with cellular proteins, including p105RB, p58cyclin A and p33cdk2. We show that in normal rat kidney 49F (NRK) cell lines expressing various mutant Ad5-E1A genes, CR2-, but not CR-1-, deletion mutants induce a typical transformed phenotype as characterized by morphology, absence of density arrest and loss of serum requirement. This indicates that induction of these transformed properties is a function of CR1. The fact that E1A proteins with deletions in CR2 show a greatly reduced association with RB, cyclin A and p33cdk2 suggests that these associations are dispensable for E1A-mediated transformation of NRK cells. Induction of the transformed properties is accompanied by a CR1-dependent increase in Proliferating Cell Nuclear Antigen and cyclin A gene expression. Elevated mRNA and protein levels of cyclin A were also found in Ad12-E1 transformed NRK cells but not in ras-transformed NRK cells. On the other hand, cyclin D expression is decreased in a CR1-dependent manner. Although Ad5-E1A proteins are sufficient to transform NRK cells, further deregulation of growth is obtained when Ad5-E1B proteins are co-expressed. One of the Ad5-E1B effects is the sequestration of the p53 protein into a cytoplasmic body containing the p53/Ad5-E1B-55 kD complex. Interestingly, in NRK cell lines expressing Ad5-E1B-55 kD, cyclin A could be detected not only in the nucleus but also in the cytoplasmic bodies. These results indicate that the deregulation of cell cycle control by the Adenovirus-E1 region may be due to a CR1-dependent alteration of the expression of cyclins A and D. PMID- 8510924 TI - TATA-box dependent trans-activation of the human HSP70 promoter by Myb proteins. AB - The oncogene v-myb and its cellular progenitor c-myb encode nuclear, DNA-binding phosphoproteins that function as transcriptional regulators. Previous studies have demonstrated the existence of two distinct transactivation mechanisms for Myb-inducible promoters. One of these mechanisms, exemplified by the chicken mim 1 promoter, involves specific binding of Myb protein to Myb binding sites located upstream of the transcriptional start site. A second mechanism, exemplified by the human HSP70 promoter, does not require the presence of specific Myb binding sites. Here, we have more closely investigated transactivation of the human HSP70 promoter by Myb proteins. Mutational analysis of the human HSP70 promoter failed to show a correlation between Myb-inducibility and the presence of a particular upstream transcription factor binding site, but instead showed that Myb inducibility was dependent on the presence of a particular type of TATA-box. This suggests that the TATA-box is involved in transactivation by v-Myb and that only a subset of TATA-boxes confers Myb-inducibility. Activation of the HSP70 promoter is dependent on the presence of most of the carboxy terminal amino acid sequences of v-Myb, including the previously identified acidic transactivation domain and a putative leucine-zipper region. Finally, we show that the HSP70 promoter is activated in a Myb binding site independent fashion not only by v-Myb, but also by chicken c-Myb and chicken B-Myb. These observations raise the possibility that the ability to transactivate in a Myb binding-site independent manner is a common property among Myb proteins. Since chicken B-Myb has been shown previously to be unable to transactivate a Myb binding-site containing promoter, such as the mim-1 promoter (Foos et al., 1992), our results also show that both modes of transactivation are independent of each other. PMID- 8510925 TI - Transactivation of GATA-1 promoter with ETS1, ETS2 and ERGB/Hu-FLI-1 proteins: stabilization of the ETS1 protein binding on GATA-1 promoter sequences by monoclonal antibody. AB - Ets family proteins activate transcription via binding to the GGAA core sequence located in the promoter/enhancer elements of many cellular and viral genes. GATA 1 is an erythroid-specific transcription factor. The promoter of the chicken GATA 1 gene contains multiple ets binding sites (EBS), two of them are present in palindromic form. The GATA-1 promoter has been shown to be activated by the E26 virus. In this study, we have analysed whether the palidromic EBS of the chicken GATA-1 promoter is a target for binding and activation by members of the cellular ets gene family products. The results herein indicate that both EBS in the palindrome are required for DNA-binding because mutations in either site reduces the activity by at least 95%. Moreover, DNA binding of ETS1 to the EBS palindrome is dramatically stabilized in the presence of a specific monoclonal antibody whose epitope maps between amino acid positions 240-260. Although each of the single sites bind, the efficiency of binding is extremely low. Furthermore, for efficient binding the two sites must be in an inverted configuration because of the fact that the oligonucleotide containing the left and right EBS in the same orientation binds 10-fold less than the oligonucleotide containing the EBS palindrome. Additionally, we show that the transcription of a reporter gene (CAT) either linked to the GATA-1 EBS palindrome or GATA-1 promoter can be activated by cotransfection with ETS1, alternatively-spliced ETS1, ETS2 or ERGB/Hu-FLI-1 expression vectors. PMID- 8510926 TI - Five novel avian Eph-related tyrosine kinases are differentially expressed. AB - We have identified cDNA clones that encode five new avian receptor-like tyrosine kinases of the Eph subclass, by screening two chicken embryonic cDNA libraries with DNA probes. We have designated them Cek6 to Cek10. The identification of these kinases indicates that the Eph subclass comprises at least 10 members and, therefore, represents a very large family of receptor-like tyrosine kinases. Variants of Cek10 and of Cek5 (a previously identified Eph-related kinase) containing amino acid insertion sequences in the juxtamembrane domain were also isolated. The Cek5 variant is expressed in the brain, but not in other tissues of the 10-day chick embryo. Analysis of 10-day chick embryo mRNAs shows the newly identified tyrosine kinases to be all expressed in both the embryonic brain and body tissues. In adult tissues, they display distinct patterns of expression. Cek6, Cek7, Cek8, Cek9 and Cek10 are likely to play significant roles in embryonic signal transduction pathways, including those involved in neural development. Their distinct tissue distributions in the adult suggest that the different members of the Eph family may each serve specific functions. PMID- 8510927 TI - Mutant p53 proteins have diverse intracellular abilities to oligomerize and activate transcription. AB - Accumulating evidence supports the hypothesis that tumor-suppressor p53 can act as a transcriptional activator. Insertion of high-affinity p53 DNA binding sites upstream of a promoter yields a p53-responsive vector. Chimeric proteins fusing p53 and the GAL4 DNA-binding domain demonstrate the presence of a transcriptional activating domain in the N-terminus of p53. GAL4-p53 chimeras constructed using naturally occurring p53 mutations at either codon 141 (Tyr-141) or 175 (His-175) of p53 had little ability to activate the reporter gene; in contrast, mutations at either codon 248 (Trp-248) or 273 (His-273) produced greater transcriptional activities than did wild-type p53. GAL4 chimeras can be used to analyse interactions between different domains of p53 and between different p53 alleles; a DNA binding site is defined, and a simple measurement can be made of function. We had expected that coexpression of GAL4 chimeras and p53 alleles would squelch transcriptional activation downstream of GAL binding sites. Surprisingly, coexpression of either p53 (Trp-248) or (His-273) with the GALA-p53 (wild-type, His-273, Trp-248, His-175, Tyr-141) effectors conferred an increase in transcriptional activation as compared with the effector alone. Oligomerization of p53 alleles with GAL4-p53 chimeras could underlie this effect, leading to an increase in transcription-activating motifs near the promoter. To test this possibility, we constructed a GAL4-p53 C-terminal chimera with p53 residues 160 393, lacking the transcriptional activating domain but retaining regions believed to be important in p53 oligomerization. Neither GAL4-p53 (C-terminus) nor p53 expression vectors were able to transactivate G5E1B-CAT alone. Both p53 (His-273) and (Trp-248) co-expressed with GAL4-p53 (C-terminus) were able to transactivate the G5E1B-CAT reporter gene; in contrast, p53 (Tyr-141) was not able to activate transcription. p53 (Tyr-141/His-273) behaved as a dominant negative mutant and inhibited the ability of the combination of p53 (His-273) and GAL4-p53 (C terminus) to stimulate the reporter gene. Double immunoprecipitation by sequentially using GAL4 and p53 antibodies showed that p53 (His-273) and (Tyr 141/His-273), but not p53 (Tyr-141), can efficiently oligomerize in vivo to the C terminal region of p53. Transcriptional activating function of p53 may be modulated by oligomerization; some mutations, such as His-273 and Trp-248, participate in these functions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8510928 TI - Alternative splicing of the chicken c-myb exon 9A. AB - The c-myb gene products are thought to be regulators of cellular replication and of differentiation and heterogeneity may underlie their multiple functions. To investigate the possible existence of heterogeneity we have examined the chicken c-myb mRNAs by Northern blot analysis and polymerase chain reaction amplification of cDNAs (RT-PCR). Northern blot analysis with the c-myb cDNA clone pSG3, which contains the entire open reading frame (ORF) plus 500 base pairs of 3' untranslated sequences (Gerondakis & Bishop, 1986), and genomic probes revealed c myb RNA species of 4.3 kb in addition to the major 4.0 kb species. The 4.3 kb c myb RNA contained the alternatively spliced exon 9A which is highly conserved and has also been detected in a minor 4.3 kb alternatively spliced c-myb mRNA in murine and human cells. Sequencing of the avian exon 9A revealed 360 bp exon homologous to that found in murine and human mRNAs, which contains three highly conserved sequence regions shared by all three species. RT-PCR demonstrated usage of exon 9A in five hematopoietic tissues and revealed an additional splicing variant which used the 3' portion of exon 9A. Northern blot analysis using splice site-specific oligonucleotide probes spanning the two splice junctions between exon 9 and 9A revealed four additional c-myb RNAs of 4.4 kb, 2.2 kb, 2.0 kb and 1.4 kb. PMID- 8510929 TI - Gene-regulatory properties of Myc helix-loop-helix/leucine zipper mutants: Max dependent DNA binding and transcriptional activation in yeast correlates with transforming capacity. AB - Max is a basic helix-loop-helix/leucine zipper (bHLH/LZ) protein that forms sequence-specific DNA-binding complexes with the c-Myc oncoprotein (Myc). Using Saccharomyces cerevisiae, we have shown that the Max bHLH/LZ domain enables Myc to activate transcription through CACGTG and CACATG sequences in vivo, and that the number and context of such sites determines the level of activation. In addition, we have used yeast to investigate the role of the Myc helix-loop-helix (HLH) and leucine zipper (LZ) motifs in mediating Max-dependent DNA-binding and transcriptional activation in vivo using HLH/LZ mutants generated by site directed mutagenesis. The results show that, while both motifs are essential for Myc to activate transcription, helix 2 of the HLH together with the contiguous LZ suffice to mediate complex formation with Max, whilst helix 1 is essential for sequence-specific DNA binding of Myc-Max complexes. Furthermore, the ability of Myc HLH/LZ mutants to bind DNA and activate transcription in collaboration with Max correlates closely with their neoplastic transforming activity in higher eukaryotic cells. PMID- 8510930 TI - Two wnt genes in Caenorhabditis elegans. AB - wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain reaction-based screen of genomic DNA, and the second, Ce-wnt-2, was fortuitously encountered in a survey of clones in a cDNA library by the Caenorhabditis Genome Project. Full-length or nearly full-length cDNAs representing both mRNAs encode proteins that are similar in length, sequence and functional domains to other Wnt proteins. Primary products of 372 and 362 amino acids begin with a hydrophobic signal peptide, include two potential N-linked glycosylation sites and contain the 22 cysteine residues conserved throughout the wnt family. In contrast to mammalian and insect wnt genes with four or five exons and conserved intron-exon boundaries, Ce-wnt-1 has nine coding exons; only one of the eight identified introns interrupts the coding sequence at a position homologous to an intron position in other wnt genes. The major transcript derived from Ce-wnt-1 is 1.4 kb in length, and the 22 nucleotides at its 5' end are added by a trans-splicing mechanism. Ce-wnt-2 is also expressed via a single major transcript, 1.5 kb in length. Both RNAs are detectable in all larval forms and adults, but they are most abundant at the embryonic stage. Ce-wnt-1 is localized to the left arm of chromosome II and Ce-wnt-2 maps to a cluster of genes on chromosome IV. PMID- 8510931 TI - New human erg isoforms generated by alternative splicing are transcriptional activators. AB - The erg gene is a member of the ets gene family. ETS proteins have been shown to bind specifically the (GGA-A/T) motif and to transactivate via this consensus sequence. The human erg products exhibit approximately 70% homology with ETS proteins in their DNA-binding domain. We have isolated three erg cDNAs from a human fetal liver library. Two of them are different from the previously described erg-1 and erg-2 cDNAs (Rao et al., Science, 1987, 237, 635-639), in the middle of their coding sequence and in their 5' part where a novel initiation codon is introduced. These isoforms are generated by alternative RNA splicing from a single gene that leads to the inclusion or exclusion of different exon sequences. The three cDNAs expressed by an in vitro transcription-translation system direct the synthesis of proteins of approximately 38, 49 and 55 kDa. These in vitro erg products were tested for their DNA-binding activity by gel mobility shift assays with different probes containing the ETS-specific binding site. The results indicated that all these erg isoforms are able to bind the ETS binding site in a specific manner. Our data using transient transfection assays indicate that erg protein isoforms function as transcriptional activators. PMID- 8510933 TI - In vivo viral and cellular Jun complexes exhibit differential interaction with a number of in vitro generated 'AP-1- and CREB-like' target sequences. AB - A direct comparison of the relative DNA-binding capabilities of in vivo Jun containing complexes derived from overexpression of the highly transforming viral Jun (VJ-1 CEF), the weakly transforming chicken cellular Jun (CJ-3 CEF) or background endogenous Jun (RCAS CEF) was assessed by gel mobility-shift assays using a synthetic oligonucleotide containing the consensus sequence TGACTCA (consensus AP-1). Chicken embryo fibroblasts (CEFs) expressing background c-Jun levels (RCAS CEF) contain almost undetectable levels of c-Jun but retain significant DNA-binding activity with two distinct complexes capable of binding specifically to the consensus AP-1 site. CEFs overexpressing either v-Jun or c Jun contain these same two complexes and, while showing marked increases in Jun protein levels, do not exhibit any increase in DNA binding or transcriptional activation activity, suggesting that much of the overexpressed protein is inactive. Gel-shift assays performed in the presence of a Jun-specific antibody revealed a reduction in binding by both complexes, suggesting that each contains Jun or a Jun cross-reactive protein. Antibodies specific for Jun B, c-Fos, Fos B and CREB failed to interact with either complex. However, antibody specific for Fra-2 caused a slight supershift, suggesting that one or both complexes may contain Fra-2. Gel-shift competition assays with 16 'AP-1- and CREB-like' target sequences revealed that, within each cell type, the two protein complexes varied in their ability to recognize the mutant target sequences. These results clearly indicate differences in potential target recognition by each specific in vivo complex, and suggest that each may preferentially bind its own subset of target DNAs. In addition, a comparison of binding by individual complexes derived from CEFs overexpressing v-Jun and c-Jun also revealed differences in target recognition. Thus, in vivo complexes formed by overexpression of v-Jun and c-Jun vary in their ability to recognize and bind to a number of 'AP-1- and CREB-like' target sequences. This has important implications with regard to the mechanisms involved in cell transformation by v-Jun. PMID- 8510932 TI - Mitogenesis of quiescent chick fibroblasts by v-Src: dependence on events at the membrane leading to early changes in AP-1. AB - Activation of rapidly reversible temperature-sensitive (ts) v-Src in quiescent chicken embryo fibroblasts (CEFs) results in both morphological transformation and exit from G0 to G1, resulting in mitosis. This phenomenon permits examination of cellular responses very soon after activating the oncoprotein, and we have used this to study changes in endogenous AP-1, and the regulation of its major components, in the first few hours after activating v-Src. This approach contrasts with a number of studies that have demonstrated enhanced activity of exogenously added AP-1 components in cells transformed by v-Src. Reactivation of a membrane-associated tyrosine kinase (tsRCAN-29) results in a several-fold increase in AP-1 DNA binding and a similar increase in the activity of an AP-1 responsive reporter soon after temperature shift. c-Jun and c-Fos are regulated at a number of levels in response to both stimuli. In quiescent RCAN-29-infected CEFs stimulated into cycle by shift to permissive temperature, c-fos transcripts are elevated by 15 min and remain above basal level for at least 4 h. Serum induces much greater elevation of c-fos transcripts, although this response is transient. Despite the difference in magnitude of the transcript responses, the stimulation of nuclear c-Fos protein is similar in both serum and v-Src stimulated cultures. No elevation in c-jun transcripts or nuclear c-Jun protein level is evident in v-Src-stimulated quiescent CEFs. However, there is an early change in the tryptic phosphopeptide map of p39 c-Jun in response to both v-Src and serum. Upon stimulation we observed a novel redistribution of phosphate in the carboxy-terminal tryptic phosphopeptide that may be responsible in part for the increase in AP-1 DNA binding. Phosphorylation of amino-terminal serines 63 and 73 on peptides Y and X, believed to be responsible for regulation of the transactivation function of c-Jun, is constitutively high in resting CEF cultures; stimulation with serum or v-Src results in only a modest increase in phosphorylation at these sites. Significantly, reactivation of a non myristylated, transformation-defective version of the tsRCAN-29 v-Src protein (RCAN-29A2) is unable to induce resting CEFs to re-enter cycle. In addition, this mutant fails to induce early increases in AP-1 activity, implying that these nuclear changes require crucial signalling events at the cell periphery, and that these events correlate with the biological consequences of expression of v-Src. PMID- 8510934 TI - Differential effect of HTLV infection and HTLV Tax on interleukin 3 expression. AB - To characterize the interactions between human T-cell leukemia virus (HTLV) infection and cellular gene expression, we examined the expression of the lymphokine interleukin 3 (IL-3) in the presence and absence of HTLV infection. IL 3, like granulocyte-macrophage colony-stimulating factor (GM-CSF), is produced by activated but not resting T cells, but although GM-CSF is constitutively expressed in HTLV-infected T cells IL-3 mRNA cannot be detected in either unstimulated or mitogen-stimulated HTLV-infected cells by polymerase chain reaction (PCR) analysis. In contrast, transient co-transfection studies with an IL-3 promoter-CAT reporter gene and an HTLV-II Tax expression construct demonstrate that Tax can transactivate the IL-3 promoter in HTLV-uninfected T cells. To determine whether differences in IL-3 promoter-binding proteins present in HTLV-infected and uninfected T cells account for this discrepancy, DNAase I footprinting of the IL-3 promoter was performed. Although crude nuclear extracts from both cell types protected the IL-3 sequences located between base pairs -168 and -125, the sequences between -125 and -103, which contain the lymphokine consensus sequences CK-1 and CK-2, were protected by extracts from HTLV-infected but not HTLV-uninfected T cells. Deletion of the region containing the CK-1 and CK-2 sequences from an IL-3 promoter CAT construct resulted in a sixfold rise in promoter activity in HTLV-infected but not uninfected T-cell lines, indicating that this region participates in the repression of IL-3 gene expression in HTLV infected T cells. PMID- 8510935 TI - The 5' and 3' non-coding sequences of the c-myc gene, required in vitro for its post-transcriptional regulation, are dispensable in vivo. AB - We have previously shown that in vivo the steady-state level of c-myc mRNA in different quiescent organs and its induction in the early stages of hepatic regeneration and after inhibition of protein synthesis are mainly controlled by post-transcriptional mechanisms. In order to localize the target sequences for these mechanisms, transgenic lines expressing various versions of the human c-myc proto-oncogene have been constructed. To avoid all possible transcriptional controls due to the c-myc 5' regulatory region, the c-myc genomic sequences were fused to MHC H-2Kb class I regulatory sequences, which have previously been shown to be able to drive reporter gene expression in most adult tissues. The transgenes contained either all human c-myc genomic sequences or were deleted for one of the sequences which have been shown in in vitro experiments to play a role in c-myc mRNA stabilization, in particular exon 1, intron 1 and the 3' non-coding region. Several independent transgenic lines were derived for each construct. Using S1 nuclease protection analysis, we have monitored H-2K, mouse c-myc and transgene mRNA expression in several quiescent adult organs, at the start of liver regeneration and after inhibition of protein synthesis in each transgenic line. Our results indicate that the 5' non-coding sequences, including exon 1 and intron 1, and the 3' untranslated region are all dispensable in the different aspects of c-myc post-transcriptional regulation. PMID- 8510936 TI - Xenopus A-myb is expressed during early spermatogenesis. AB - c-myb has been studied intensely, but other members of the myb gene family have been largely overlooked. This paper describes the isolation and characterization of a Xenopus cDNA sequence, XAMyb, closely related to human A-myb. Xenopus provides a valuable experimental model for investigating the involvement of genes in cell proliferation, differentiation and development. Although no expression of XAMyb was detected in oocytes or eggs or during early embryogenesis, there is a low level of expression within ovarian tissue, which is down-regulated in response to hormones that stimulate oocyte maturation. However, in adult male Xenopus, virtually all A-myb expression is in the testis, particularly within the nuclei of spermatogonial cells, the mitotically proliferating early progenitors of spermatozoa. Expression falls dramatically during meiosis and is virtually undetectable during subsequent spermiogenesis. This pattern of expression of Xenopus A-myb during the preterminal differentiation/proliferation phase of germ cell development resembles the expression of c-myb in similar phases during haematopoiesis. These results suggest related roles for myb variants during the development of different stem cell-derived populations. PMID- 8510937 TI - Mutation of a phenylalanine conserved in SH3-containing tyrosine kinases activates the transforming ability of c-Abl. AB - c-abl is the normal cellular homolog of the v-abl transforming gene of Abelson murine leukemia virus. By constructing recombinants between c- and v-abl retroviruses, we show that a point mutation in c-Abl is sufficient to change the myristoylated form of c-Abl into a protein able to transform fibroblasts, but not capable of transforming bone marrow or inducing Abelson disease. This activating mutation, which changes the phenylalanine at amino acid 420 to valine (F420V) found in the homologous position of v-Abl, is positioned outside of the SH3 domain, a region typically modified in transforming alleles of abl. Phenylalanine 420 is perfectly conserved among tyrosine kinases with N-terminal SH3 domains (the Src and Abl families). The equivalent position in other protein tyrosine kinases is a conserved hydrophobic residue that predicts the specific family to which that kinase belongs. Mutation of phenylalanine 420 to other hydrophobic residues activates c-Abl. Unlike other transforming variants of Abl, the F420V mutant protein is not highly phosphorylated on tyrosine. Mutation of the nearby proposed autophosphorylation site, tyrosine 412, shows that this tyrosine is not strictly required for fibroblast transformation in either F420V or SH3-deleted variants of c-Abl (IV). PMID- 8510938 TI - The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential. AB - The acute retrovirus AKT8, isolated from an AKR mouse T-cell lymphoma, transforms mink lung cells in culture and is oncogenic when inoculated into newborn mice. The oncogene carried by this virus, v-akt, arose by recombination between Gag and the 5' untranslated region of the cellular gene c-akt. v-akt encodes a 105 kilodalton (kd) Gag-Akt fusion protein which is phosphorylated on serine and threonine residues. c-akt encodes a 55 kd serine-threonine protein-kinase, which is related to members of the protein kinase C (PKC) family and contains an SH2 like domain. The SH2-like and catalytic domains of Akt were expressed in E. coli as fusions to the carboxy-terminus of the Maltose binding protein (MBP). Antibodies against these proteins were raised in rabbits and they were used to determine the potential myristylation and subcellular localization of the v-akt and c-akt protein products. Immunoprecipitation of v-akt and c-akt from lysates of [35S]methionine and [3H]myristic acid labeled AKT8 transformed mink lung cells revealed that only v-akt was myristylated. Fractionation of Dounce-homogenized cellular extracts from uninfected and v-akt-transformed mink lung and PA317 cells and from uninfected PC12 cells by differential centrifugation showed that while the c-akt protein was localized primarily in the cytosol (90%), the v-akt protein was dispersed among the cellular compartments with approximately 40% on the plasma membranes, approximately 30% in the nucleus and approximately 30% in the cytosol. To determine whether the differences in post-translational modification and subcellular distribution between c-akt and v-akt translated into oncogenicity differences between the two proteins, we used retrovirus based constructs to express them both in the nontumorigenic rat T cell lymphoma line 5675. Intraperitoneal (IP) inoculation of the parental and c-akt expressing 5675 cells in nude Balb/c mice revealed that neither was oncogenic. In sharp contrast to these results, v-akt expressing 5675 cells inoculated in nude Balb/c mice were found to be highly oncogenic. PMID- 8510939 TI - Organization and analysis of the promoter region and 5' non-coding exons of the human c-src proto-oncogene. AB - In order to help clarify the cellular mechanisms that regulate expression of the human c-src proto-oncogene, we have isolated a series of overlapping genomic clones that contain the c-src promoter region, as well as three previously uncharacterized exons. These exons encode the 350-bp 5' untranslated region of the c-src mRNA and span 35 kb of genomic DNA, extending the human c-src locus to approximately 60 kb. Subcloning and sequence analysis of the 5' flanking region of the gene revealed a high GC content and several consensus Sp1 and AP2 binding sites. However, TATA or CAAT boxes were not present, a characteristic shared by other GC-rich promoters. Promoter-CAT constructs demonstrated that the promoter was functional in transfection assays and that its activity was dependent on correct orientation. CAT-promoter deletion constructs were used to define the 5' boundary for maximal promoter activity and to reveal the presence of both positive and negative regulatory elements. S1 analyses of human c-src mRNA from cell lines indicated that multiple transcription start sites were utilized. PMID- 8510940 TI - Characterization of a c-met proto-oncogene activated in human xeroderma pigmentosum cells after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). AB - Human xeroderma pigmentosum (XP) fibroblasts were transformed with N-methyl-N' nitro-N-nitrosoguanidine (MNNG). The transformed cells, called ASKMN, were immortalized, grew in agar and were tumorigenic in nude mice. A trp-met oncogene was identified in ASKMN cells, after transfection of high molecular weight DNA on 3T3 mouse cells. The ASKMN cells and the 3T3 transformants expressed the 5-kb mRNA transcribed by the tpr-met oncogene and its p65tpr-met phosphorylated protein. Using the polymerase chain reaction (PCR) technique followed by hybridization with synthetic probes or direct sequencing, we showed that the sequence encompassing the 'rearranged breakpoint' was the same as that previously described in the tpr-met oncogene present in the MNNG-HOS cells. However, G to A transitions found in the tpr or met sequences of the ASKMN oncogene, probably the result of the specific mutagenic activity of MNNG, were absent in the MNNG-HOS gene. Apparently normal chromosomes 1 and 7 were identified in the ASKMN cell metaphases using several cytogenetic techniques. PMID- 8510942 TI - Rigid lens fitting made easier using a modified keratometer. AB - After simple modification, a keratometer can measure both the central and peripheral regions of the cornea. The apical radius and p-value of the cornea can be determined with this information using a computer program. This computer program suggests lens parameters similar to those chosen by conventional methods in rigid lens fitting. The computerized fitting method is also applicable to Chinese subjects. PMID- 8510941 TI - Partially transformed T3T3 cells express high levels of mutant p53 in the 'wild type' immunoreactive form with defective oligomerization. AB - High levels of wild-type p53 suppress transformed growth of many cell lines and yet murine T3T3 cells shown partially transformed growth despite high endogenous levels of phenotypically 'wild-type' p53. On sequencing T3T3 p53 was found to encode missense mutations at codons 230 and 287 and, although endogenous T3T3 p53 is 'wild type', the protein adopted the mutant phenotype when expressed in vitro. Size fractionation of T3T3 cell lysate indicated monomeric p53 possibly in complex with a low molecular weight protein. When expressed in vitro T3T3 p53 formed dimers and higher order structures. Thus T3T3 cells appear (i) to drive endogenous mutant p53 to adopt conformational epitopes characteristic of the 'wild-type' protein, and (ii) to interfere with normal assembly of p53 quaternary structure. Phosphopeptide mapping of p53 from 3T3x cells, T3T3 cells and SV3T3 cells indicated reduced amino terminal phosphorylation of the mutant p53 phenotype. Alternative splicing of p53 was also detected in 3T3x cells; similar splicing occurs in wild-type p53 (Han & Kulesz-Martin, 1992; Nucl. Acids Res., 20, 1979-1981) and a possible regulatory function is discussed. PMID- 8510943 TI - Reliability of high- and low-contrast letter charts. AB - The aim of this study was to measure the reliability, in test score units, of several clinical tests which use high- and low-contrast letters, and to provide an estimate of what constitutes a significant change in performance over time. Patients with normal vision and with early or subtle eye disease were recruited so that the results would be representative of the population likely to present for primary vision screening. Patients were tested on the Bailey-Lovie logMAR chart, the Regan low-contrast letter charts and the Pelli-Robson low-contrast letter chart on two occasions; the two test sessions were separated by at least four weeks to give an estimate of reliability appropriate for the conditions under which the tests are likely to be used. A 'significant change', i.e. one which would be observed in only about 5% of patients with stable visual performance, was about +/- 2 'steps' of the measurement scale, i.e. +/- 2 lines for the Bailey-Lovie and Regan charts and +/- 2 letter groups for the Pelli Robson chart. PMID- 8510944 TI - Fixation disparity at different viewing distances of a visual display unit. AB - Fixation disparity was measured while subjects observed a realistic alphanumeric pattern on the cathode ray tube (CRT) of a visual display unit at viewing distances of 25-85 cm. The psychometric function of fixation disparity was determined by analysing the observers' responses to a series of short (100 ms) flashes of nonius targets that were superimposed on the CRT-image by means of a half-silvered mirror. Test-retest correlation of fixation disparity was high (r = 0.8) at viewing distances of 40 and 82 cm and lower (r = 0.55) at the shorter distance of 26.5 cm. Mean fixation disparity increased to a more exophoric condition as the display approached the eyes. However, this effect was observed only in some of the subjects, so the susceptibility of fixation disparity to viewing distance appears to be an individual characteristic. When subjects observed the VDU screen continuously for 30 min at viewing distances of 85, 47, 31 and 25 cm in different sessions, fixation disparity and accommodation remained unchanged over time. PMID- 8510945 TI - Population distribution of stereoscopic ability. AB - Of 188 unselected biology students participating in one or both of two tests measuring stereoscopic depth detection ability, 183 (97.3%) were able to see a depth difference at horizontal disparities of 2.3 min arc or smaller. At least 80% could detect depth differences at 30 sec arc disparity. These findings indicate that most people are able to take advantage of the increasing utilization of stereoscopic displays. PMID- 8510946 TI - Survey of the accuracy of new pseudoisochromatic plates. AB - The accuracy of three new pseudoisochromatic tests for detecting red-green colour deficiency was assessed. These were the Ishihara plates, the Ishihara test for 'unlettered persons' and Ohkuma's test cards. We examined 500 subjects; 471 normal trichromats and 29 colour-deficient people. Results obtained for the 1989 edition of the Ishihara plates were compared with the 9th edition and the most efficient plates identified. Although normal trichromats may be expected to make several interpretive misreadings, the Ishihara plates were found to be superior to the 9th edition and to the Ohkuma test (1986) for colour vision screening. The new symbol designs of the Ishihara plates for 'unlettered persons' (1990) were found to be very effective for colour vision screening, and a further study with young children is proposed. The 38 plate 1989 edition of the Ishihara test is recommended for use in clinical practice. The designs included in the concise 24 plate edition and the new abbreviated 14 plate edition are not selected from the point of view of accuracy and more reliable results are obtained if the full test is given or if the practitioner shows only the most efficient designs. PMID- 8510947 TI - Structural model for emmetropic and myopic eyes. AB - A structural model for the eye was tested using refractive component data for 42 emmetropic eyes (-0.50 to +1.50 D) and 42 eyes having from 5.00 to 7.00 D of myopia. Parameter estimates derived by applying the structural model to emmetropic eyes and to myopic eyes demonstrated that a common model described the two types of eyes, but that emmetropic eyes and myopic eyes could be considered to belong to statistically discrete populations. Corneal radius and vitreous chamber depth were the most important components determining refractive state. PMID- 8510948 TI - Initial control component in disparity vergence eye movements. AB - Recent experimental evidence indicates that a portion of the oculomotor response to disparity stimulation is functionally open-loop; that is, the response occurs without the aid of visual feedback. To investigate the stimulus features that elicit or influence this dynamic movement, convergence responses to a step, a step followed by target disappearance, and a pulse followed by target disappearance were obtained from four subjects using infrared oculography. The target was a thin vertical line (0.25 degrees) either 2 or 10 degrees in height. Stimuli having different amplitudes (1, 2, 4 and 8 degrees) and disappearance times (50, 100 and 200 ms) were selected randomly along with occasional divergent stimuli to minimize prediction and voluntary vergence. Experiments showed that the dynamic characteristics of the initial portion of the response were essentially the same, even when the target disappeared before the movement took place. The magnitude of the initial response depended on the stimulus amplitude, but was not influenced by either stimulus duration or target height. For example, stimulus durations as short as 50 ms elicited responses similar to those caused by standard steps. The initial response was shown to be active over a well defined time period of about 200 ms, after which the response appears to be mediated by a visually-guided control component. These results support the recently developed dual-mode theory of vergence control in which an initial preprogrammed (open-loop) control component is followed by a feedback (closed loop) controlled component which reduces any remaining disparity. PMID- 8510949 TI - Colour vision anomalies following experimental glaucoma in monkeys. AB - Spectral sensitivity defects, associated with chronic elevated intraocular pressure (IOP) produced by Argon laser trabeculoplasty, were studied in monkeys. Increment-threshold spectral sensitivity (ITSS) and threshold versus intensity (TVI) functions were measured using a behavioural model. Elevated IOP resulted in short wavelength (SW) sensitivity losses characteristic of many ocular diseases. The amount of SW sensitivity loss for ITSS functions depended upon the intensity level and chromatic composition of the background field. The optimum condition identifying the greatest SW sensitivity reduction was a yellow background of moderate intensity (100-1000 Td). In the early stages of experimental glaucoma, the cone mechanisms and the rod mechanism typically showed decreased test and field sensitivities. The SW cone pathway has slightly greater threshold elevation (approximately 0.3 log unit) compared to the rod and cone pathways. On the other hand, in the advanced stages of experimental glaucoma, the largest sensitivity losses were in the longer-wavelength, red-green opponent mechanisms, with the rod and SW cone pathways showing smaller losses. The similarities of the colour vision anomalies in this animal model with those of patients with glaucoma, provides support for its use as an experimental model for human glaucoma. PMID- 8510950 TI - Mathematical models of the general corneal surface. AB - Although the curvature of the general cornea's two principal meridians can be acceptably modelled (within limits) by ellipses, this is insufficient to delineate the overall corneal surface. Applying different assumptions in either case, two corneal models are advanced which interpolate x, y, z points over the whole corneal surface, dependent only on the specifications of the plane curves of the principal meridians. PMID- 8510951 TI - Astigmatism, accommodation, the oblique effect and meridional amblyopia. AB - The variation with accommodation in the dimensions of the geometrical blur ellipse that is formed on the retina of the astigmatic eye is explored in relation to orientation dependence of the corresponding line-spread function (LSF) and modulation transfer function (MTF). It is shown that if theta is the orientation of the line or grating with respect to the more powerful meridian of an eye having C dioptres of astigmatism, the optimal accommodation response varies as 0.5 C cos2 theta. The analysis is extended to include the effects of diffraction. Even at optimal focus, the diffraction-limited MTF at 45 degrees to the principal meridians of an eye with small amounts of astigmatism is substantially degraded. For example, with a 3 mm pupil and only 0.50 DC of astigmatism, the first zero in monochromatic modulation transfer at 555 nm occurs at approximately 32 c/deg in the oblique meridian as compared with 94 c/deg in the principal meridians. The results are used as the basis of a discussion of the possible role of infant and juvenile astigmatism in the development of the oblique effect and of meridional amblyopia. PMID- 8510952 TI - Vision of the famous: the artist's eye. AB - This article reviews the possible effects of various acquired or inherited eye disorders on the paintings and sculptures of some of the most famous artists. Were Leonardo da Vinci, Rembrandt, Michelangelo and Monet affected by age-related eye disease which influenced their later works? Was El Greco's oblique elongation of his characters due to astigmatism? Was Constable a colour-defective? Was the Impressionist style of painting due to the myopia and cataract of its leading components? Are van Gogh's yellow and haloed paintings due to the ocular side effects of digitalis toxicity? These questions are discussed and some of the artists' works are shown to illustrate the points. PMID- 8510953 TI - Reading performance with low vision aids: relationship with contrast sensitivity. AB - Reading performance and contrast sensitivity were measured in 30 subjects with low vision due to a variety of pathologies. The Pepper test was used to quantify reading rate and accuracy with the subject's own prescribed optical reading low vision aid. It was found that both reading rate and accuracy were repeatable measures. Reading rates were found to be correlated with contrast sensitivity at 0.5 c/deg (r = 0.62). Multiple regression analysis also showed that the best predictor of reading rate was contrast sensitivity at 0.5 c/deg and that no other components of the contrast sensitivity function helped to explain more of the variance. This indicates that primarily low spatial frequencies are necessary for reading with optical low vision aids, as has been found previously for reading with a close circuit TV system. PMID- 8510954 TI - Explanation of isogyre formation by the eye lens. AB - The eye lens is considered to be birefringent and this property is thought to be responsible for the image of a cross which is formed within the lens when it is placed between crossed polarizers. This paper presents an alternative explanation for the pattern, as a phenomenon of refraction. PMID- 8510955 TI - Simplified closed circuit television magnifier for the partially sighted. AB - Although the use of closed circuit television (CCTV) magnifiers is now well established, the instruments tend to be bulky, complex and expensive. A magnifier is described which consists of a miniature TV camera used as a hand-held scanner, which can be plugged into a wide variety of monitors and television sets. PMID- 8510956 TI - Deformable spectacle lenses. AB - Although there are many designs of progressive power multifocal lenses commercially available, they all follow the same basic design concept, with the lens power varying across their aperture as a result of using one aspheric lens surface. An alternative approach was tried on an experimental basis, where the variation in power is produced by a liquid-filled deformable lens. PMID- 8510957 TI - Computer technology can enhance patient care. PMID- 8510958 TI - A proposal for using generics. PMID- 8510959 TI - Continuing the participation debate. PMID- 8510960 TI - What's new for the medical consultant. AB - The role of the medical consultant caring for the surgical patient has evolved over the last 20 years as numerous books and articles have contributed to the knowledge base of this field. Consultants used to merely "clear" patients for surgery. Now, guidelines based on data are available to direct many perioperative management decisions. The consultant is responsible for knowing the ever-growing body of literature and for conducting himself or herself according to accepted guidelines for consultation. PMID- 8510961 TI - Physicians to play key role in halting the new TB threat. Pennsylvania Medical Society Commission on Public Health. AB - In response to grave concern of Society members about the current and potential impact of the resurgence of tuberculosis on the health and well-being of the people of Pennsylvania, the Commission on Public Health in a position paper outlined Society concerns and suggested ways to halt the new threat of this once pervasive and dreaded disease. This article is an excerpt of that paper. PMID- 8510962 TI - The physician's role in preventing nicotine addiction. Interview by Juli C. McGreevy. AB - Ralph E. Stolz, DO, a general practitioner in Emmaus, devotes 50 percent of his practice to the treatment of addictions to drugs and behaviors. Dr. Stolz is a member of the American Society of Addiction Medicine and medical director of addiction services at Allentown Osteopathic Medical Center. PMID- 8510963 TI - What our enemies are really after: the other 90 percent. AB - As statistics have shown, physician income accounts for approximately 10 cents of the "health care dollar." But in this editorial, a Society trustee questions whether the real issue is not that 10 cents, but rather control of the other 90. PMID- 8510964 TI - Reform legislation: potential implications for physicians. PMID- 8510965 TI - The CEO-physician: key to thriving group practice. PMID- 8510966 TI - Are PROs worth their costs? PMID- 8510967 TI - The business of patient care. Interview by David Fox. PMID- 8510968 TI - HIV hotline for health care providers. PMID- 8510970 TI - Preventive law monthly. Are you an effective complainer? PMID- 8510969 TI - Celebrating one hundred years 1903-1993. Public health: a nurse's viewpoint. PMID- 8510972 TI - Featuring--Criticare. PMID- 8510971 TI - Florence Nightingale in verse. PMID- 8510973 TI - The Pennsylvania Higher Education Nursing Schools Association: advancing nursing education in the Commonwealth. PMID- 8510974 TI - Economics & General Welfare Chair Cook speaks before governor. PMID- 8510975 TI - Violence against nurses. PMID- 8510976 TI - Professional malpractice insurance. PMID- 8510977 TI - Nursing makes contribution in acute care. PMID- 8510978 TI - Oral streptococcal colonization of infants. AB - The objective of this study was to determine the prevalence and proportions of different streptococcal species among the streptococcal flora during infancy. A total of 60 oral samples were collected by oral swabbing of the buccal mucosa and alveolar ridges of 18 infants before tooth eruption and from buccal and lingual surfaces of teeth after tooth eruption. A total of 549 isolates on mitis salivarius agar were speciated, principally by recently revised biochemical criteria of Kilian et al. Streptococcus mitis biovar 1 predominated, both in prevalence (89%) and proportion of oral streptococci recovered in each sample (median = 87% of streptococcal flora). Streptococcus salivarius was also prevalent (94%) but generally represented a small percentage of the total streptococcal flora (median = 3%). Streptococcus oralis and Streptococcus anginosus strains were detected in approximately one third of predentate and dentate infants in the first year of life. Streptococcus sanguis strains were not detected before tooth eruption, but could be detected in 7/14 of the infants with teeth. Thus, S. mitis constitutes the major component of the initially colonizing streptococcal microbiota of the young infant. PMID- 8510979 TI - Dental plaque development on defined streptococcal surfaces. AB - Coaggregations between bacterial species have been widely studied in vitro but not in the mouth. A new in vivo assay was used to measure the rate and composition of indigenous plaque formation onto bovine enamel chips covered with a continuous layer of bacteria. Chips were covered with Streptococcus oralis ATCC 10557, which coaggregated with many oral species, or Streptococcus gordonii S7, which did not coaggregate with these oral species, and placed in the mouth for 4 and 24 h. There were no differences in the number of most indigenous bacterial species isolated from the two streptococcal surfaces. However, the number of Actinomyces viscosus as a proportion of total Actinomyces spp. was significantly different on the two surfaces at 24 h. With the exception of Actinomyces naeslundii and A. viscosus removed from the S7 surface, all indigenous species increased significantly in number from 4 to 24 h, irrespective of the streptococcal surface. This study demonstrated that interbacterial coaggregation had only a limited effect on in vivo plaque development. Thus suggesting that environmental factors, growth or other adherence phenomena are dominant in in vivo plaque formation. PMID- 8510980 TI - An analysis of the subgingival microflora in randomly selected subjects. AB - The aim of this study was to describe the presence of some microbial species in the subgingival microflora of a randomly selected subject sample. A further objective was to analyze the association between some microbiological characteristics and the periodontal conditions of the subjects. A total of 171 individuals aged 30-65 years were included. A pooled subgingival plaque sample was obtained from the mesial aspect of the 6 Ramfjord teeth by the use of the paper-point method. The samples were processed and analyzed according to standardized procedures. The periodontal condition of the subjects was examined clinically and included assessment of plaque, gingivitis, probing pocket depth and probing attachment level. The results showed that 81% of the subjects were positive for Campylobacter rectus, 80% for Fusobacterium nucleatum, 77% for Streptococcus sanguis, 72% for Streptococcus mitis, 66% for Eikenella corrodens, 58% for Prevotella intermedia, 32% for Capnocytophaga, 27% for Selenomonas, 25% for Actinobacillus actinomycetemcomitans, 14% for Porphyromonas gingivalis and 13% for Streptococcus mutans. Small differences in the periodontal conditions were observed between subjects harboring P. gingivalis, A. actinomytecomitans or > 5% P. intermedia and the rest of the sample. Similarly small differences in the clinical parameters were revealed when the subjects were grouped according to proportions of disease-associated and health-associated species in their subgingival samples. PMID- 8510981 TI - The association of carious dentin microflora with tissue changes in human pulpitis. AB - Correlations were sought between the number and type of microorganisms recovered from sampled carious dentin and the cellular responses observed in dental pulpal tissues from a sample of 65 vital, carious teeth extracted from adult humans who had declined the option of tooth restoration. Standardized homogenates of carious dentin were plated using selective and nonselective media under anaerobic and microaerophilic conditions. Pulpal responses were characterized histopathologically on the basis of the nature of the cellular infiltrate and the extent of degenerative changes. A significant association between the number of Prevotella intermedia and Prevotella melaninogenica in carious dentin and extensive, principally mononuclear, inflammatory infiltration was evident despite a high degree of complexity and intersubject variability in the microbial flora. There was no apparent association between other microorganisms or total microbial load and the histopathological category. PMID- 8510982 TI - Microbiology of early supragingival plaque development after delmopinol treatment. AB - The aim of this double blind, cross-over, microbiological study was to compare the effect of topical application of the plaque control agent 0.5% delmopinol HCl with placebo on early supragingival plaque formation. Six subjects underwent 7 periods (0.5, 1, 2, 8 and 24 h and 3 and 7 days) of placebo and delmopinol application, respectively. At the start of each study period the teeth were professionally cleaned and 2 ml of placebo and delmopinol 0.5%, respectively, were applied on all teeth (twice daily for periods lasting 24 h or more). At the end of each period, supragingival plaque samples of one upper and one lower buccal tooth surface were collected separately and cultured on anaerobically incubated Brucella blood agar, on aerobically incubated blood agar and on selective media for the enumeration of Streptococcus spp., Haemophilus spp., Actinomyces spp., Veillonella spp., Neisseria spp. and Fusobacterium spp. The total anaerobic cultivable microflora after delmopinol use was 10-100 times lower than after placebo use. Compared with placebo, the proportion of cultivable aerobes (61.3%), Streptococcus spp. (104.8%) and Haemophilus spp. (82.3%) increased and the proportion of Actinomyces spp. (86.1%), Veillonella spp. (60.5%), Neisseria spp. (96.9%) and Fusobacterium spp. (60.6%) decreased after 7 days. Short-term application of 0.5% delmopinol HCl on supragingival dental plaque regrowth resulted in a reduction of the number of cultivable microorganisms in the plaque and produced a shift in the cultivable plaque composition. PMID- 8510983 TI - Peptostreptococcus micros has a uniquely high capacity to form hydrogen sulfide from glutathione. AB - There are high amounts of hydrogen sulfide in deep periodontal pockets. This volatile sulfur compound may be formed from L-cysteine, but only low levels of this amino acid can be expected to be present in periodontal pockets. Glutathione, L-gamma-glutamyl-L-cysteinylglycine, is in high concentration in most tissue cells, and this tripeptide may be more readily available as a source of hydrogen sulfide formation in the pockets. The ability of 37 different species of oral bacteria to utilize glutathione in hydrogen sulfide formation was studied. Of these species, only 2 species of Peptostreptococcus and 5 species of Fusobacterium formed high amounts of hydrogen sulfide from glutathione within 24 h. Since the initial rate of hydrogen sulfide formation was more than 5 times higher in Peptostreptococcus micros than in any of the other bacterial species, the kinetics of sulfide formation from glutathione by P. micros was further elucidated. The formation of sulfide followed quite closely hyperbolic Michaelis Menten kinetics. The maximal initial rate of sulfide formation (Vmax) was 163 +/- 2 nmol sulfide per minute per milligram of cellular protein. Half maximal initial rate (Km) was obtained at 7.4 +/- 0.8 microM glutathione. The initial rate of sulfide formation from L-cysteine was much slower and was almost proportional to L-cysteine concentration. This difference in kinetics of sulfide formation between glutathione and L-cysteine strongly suggested that glutathione was actively transported into the cell, whereas the transport of L-cysteine was more or less controlled by diffusion. The sulfide formation from the dipeptide L cysteinylglycine also followed quite closely hyperbolic Michaelis-Menten kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8510984 TI - Comparison of the distribution of Actinomyces in dental plaque on inserted enamel and natural tooth surfaces in periodontal health and disease. AB - The distribution of Actinomyces naeslundii, Actinomyces viscosus and Actinomyces odontolyticus in healthy and diseased adult populations was studied in 3 different ways. First, supragingival plaque formation at 2 through 72 h was examined in 12 periodontally healthy adults using a removable pre-measured surface of enamel bonded to molars and premolars. Second, a cross-sectional examination of the composition of both supragingival and subgingival plaque of unknown age was conducted in 205 adults exhibiting periodontal health to moderate disease. Third, the effects of oral hygiene instruction and root planing on the subgingival microflora of a subset of 19 subjects with moderate periodontitis were examined. The evaluation of 12 adults revealed that the predominant species in early plaque formation (2, 4 and 8 h) was A. odontolyticus. A. viscosus and A. naeslundii were present in developing plaques in almost all subjects in 2-h plaque, but absent in half the subjects when 4-, 8- or 24-h plaque was examined. These two species significantly increased in numbers per mm2 enamel surface area in 48- and 72-h plaques. A. odontolyticus was not related to clinical signs of periodontal disease in 205 adults, and its subgingival proportions in plaque did not change following periodontal treatment of 19 individuals. A. naeslundii was found in significantly higher numbers in supragingival than subgingival plaques in the 205 adults examined. The mean proportion of A. naeslundii significantly decreased as the magnitude of probing depth and attachment loss increased. The proportions of A. naeslundii and A. viscosus were found to be significantly increased in subgingival plaques following periodontal treatment. PMID- 8510985 TI - The role of interleukin-1 alpha in the pathogenesis of periapical bone destruction in a rat model system. AB - To identify the mediators that stimulate periapical bone resorption following infection, a rat model system was used in which active (rapid) and chronic (slow) phases of bone destruction can be distinguished. Extracts of inflammatory tissues from active lesions contained high levels of bone-resorbing activity, which was destroyed by proteinase K and heat (70 degrees C), but was unaffected by polymyxin B, indicating the presence of protein mediator(s) rather than lipopolysaccharide. Fast-performance liquid chromatography gel filtration of extracts of active lesions demonstrated that most activity was associated with macromolecules of MW 30-60 kDa and 15-20 kDa, consistent with bone resorptive cytokines, including interleukin 1 (IL-1) and tumor necrosis factor (TNF). Inhibition with cytokine-specific antisera demonstrated that resorbing activity in active lesions was significantly neutralized by anti-IL-1 alpha, whereas anti IL-1 beta, anti-TNF alpha and anti-TNF beta had only slight effect. A lower amount of resorbing activity was present in extracts of chronic lesions, which was also neutralized only by anti-IL-1 alpha. Inflammatory tissue explants produced more IL-1 alpha than IL-1 beta in vitro, confirming findings with extracts, and high levels of IL-1 alpha were present in active lesions by radioimmunoassay. These data indicate that bone resorption stimulated by bacterial infection is primarily mediated by IL-1 alpha in this model. The similarity of cytokines in active and chronic lesions suggests that quantitative rather than qualitative differences in these mediators may account for lesion progression. PMID- 8510986 TI - Effects of fluoxetine on the oral environment of bulimics. AB - The purpose of this study was to evaluate in a double-blind placebo-based study the effects of fluoxetine over a period of 16 weeks on the frequency of binging and purging and on fluctuations in the levels of cariogenic organisms and saliva secretion rate of patients (n = 30) with bulima nervosa. Profile analysis suggested that, over the course of the study, binging and purging frequency and Streptococcus sobrinus salivary levels decreased significantly in the fluoxetine group as compared with the placebo group. Our finding that S. sobrinus levels decreased 16 weeks after subjects were on medication suggests that the salivary levels of these organisms could serve as an objectively measured indicator of patient compliance with antibulimic therapy. PMID- 8510987 TI - A pediatrician's view. The general pediatrician as dermatologist. PMID- 8510988 TI - Bacteriologic aspects of skin and soft tissue infections. PMID- 8510989 TI - Common bacterial skin infections in childhood. PMID- 8510990 TI - Impetigo in childhood: changing epidemiology and new treatments. PMID- 8510991 TI - Periorbital cellulitis. PMID- 8510992 TI - Fungal infections of the skin, hair, and nails. PMID- 8510993 TI - More and more it seems, "it's all in the genes". PMID- 8510994 TI - Clinical diagnosis of genetic diseases. PMID- 8510995 TI - Biochemical diagnosis of genetic diseases. PMID- 8510996 TI - Cytogenetic diagnosis of genetic diseases. PMID- 8510997 TI - Gene therapy--a primer. PMID- 8510998 TI - Glossary of genetics terms. PMID- 8510999 TI - International research and humanitarian partnerships to ease the pain. PMID- 8511000 TI - Pediatric pain assessment: validation of a multidimensional tool. AB - Prior to introducing a locally developed pediatric pain assessment tool into the ward setting, testing was done to establish its content and construct validity. Results indicated that the PMHPAT is a valid measure of pain for children between 7 and 14 years old with two limitations: (a) it is unsuitable for assessing spasmodic pain, and (b) some children are unable to distinguish between "hurting" and "feeling." PMID- 8511001 TI - Pain location: validity and reliability of body outline markings by 4 to 7-year old children who are hospitalized. AB - This descriptive study addressed the validity and reliability of a body outline for pain location assessment in 4 to 7-year-old children (n = 46) who are hospitalized. The findings support the use of a body outline for pain location in this age group. PMID- 8511002 TI - Management of children on interferon therapy. AB - This article examines current pediatric uses of interferons, including treatment of chronic granulomatous disease and hemangiomas. An overview of the normal function of interferons in included. The primary focus is on nursing education and management of children on interferon therapy. PMID- 8511003 TI - Bolstering personal control in child patients through coping interventions. AB - Beliefs about control have been shown both clinically and empirically to be associated with children's distress reactions to medical events. This article focuses on bolstering children's control through coping strategies found useful to children in ameliorating their distress responses during illness and/or hospitalization. PMID- 8511004 TI - Extended day program: bringing preschool to the hospital. AB - Children who must grow up in a hospital setting due to complex medical and social conditions present health care professionals with unique challenges that include (a) providing an environment to facilitate growth and development, (b) normalizing life experiences, (c) strengthening children's positive self concepts, (d) promoting independence and exploration, and (e) introducing opportunities for learning experiences. An Extended Day Program, designed by nurses and other professionals to promote optimal development and psychosocial care for long-term hospitalized children, can offer these benefits. PMID- 8511005 TI - Pediatric management problems. Early morning hyperglycemia with ketonuria. PMID- 8511006 TI - Involvement of educational staff in the health care of medically fragile children. AB - This study obtained information on medically fragile children (MFC) attending schools and the involvement of educational staff in their health care. Findings indicate that educators have contact with a large number of medically fragile children with a variety of health conditions that could have serious implications. Educators are being asked to perform health care tasks in the classroom, and receive little or no training to prepare them for health conditions of the children or health care procedures. Educators feel unprepared to deal with medically fragile children in the classroom, and want and need more training. PMID- 8511007 TI - Charts used in measuring growth rates need updating. PMID- 8511008 TI - Down syndrome article presents misleading information. PMID- 8511009 TI - Latex allergy needs to be monitored closely. PMID- 8511010 TI - Ronald McDonald House--The House that love built. PMID- 8511012 TI - Immunizing America's children. PMID- 8511011 TI - The accuracy of tympanic temperature measurement in children. AB - PURPOSE: To evaluate the accuracy and consistency of tympanic temperature measurement in children. METHODOLOGY: A correlational study compared tympanic temperature measurements with oral, axillary, and rectal measurements. A convenience sample of 209 hospitalized children ages newborn to 12 years was stratified according to age. Cross tabulation by fever was analyzed for sensitivity and specificity. RESULTS: Tympanic measurements were significantly correlated to oral, axillary, and rectal measurements. The correlation between axillary and tympanic in newborns was lowest. Tympanic measures identified fevers more often than oral or axillary measurements when compared to rectal measurements. CONCLUSIONS: Tympanic measurement in newborns was not sufficiently accurate. Tympanic measurements may be used routinely in children older than 3 years. PMID- 8511013 TI - Confronting unsafe practice: ethical and legal issues. AB - Confronting unsafe practices in the workplace requires careful ethical and legal analysis and a supportive practice environment. Nurses should collaborate with their colleagues to create mechanisms to review and monitor clinical practices, investigate questionable occurrences, and collaborate with licensing boards to respond to infractions. PMID- 8511014 TI - A closer look at septic shock. AB - Septicemia and septic shock are a leading cause of morbidity and mortality among hospitalized patients. Children undergoing chemotherapy, postsurgical procedures and those with AIDS are at increased risk for developing this unique type of shock. At the bedside, nurses play a pivotal role in early recognition and treatment, the key to survival. PMID- 8511015 TI - Mitochondrial disorder associated with newborn cardiopulmonary arrest. AB - A female infant who died 2.5 d after birth with hypoglycemia, lactic acidosis, and sudden multisystem failure was studied. Biochemical studies showed complex III and IV deficiency in liver, kidney, and muscle, with muscle most severely affected. Southern blot analysis of the patient's mitochondrial DNA did not reveal any deletions. Denaturing gradient gel analysis, which detects single base changes by differences in melting behavior, showed an extra band that was not seen in mitochondrial DNA from the mother, the mother's identical twin sister, or an unrelated normal subject. This extra band indicated heteroplasmy for a restriction fragment containing the apocytochrome b and transfer RNA(thr) genes. Sequencing revealed an A to G mutation at nucleotide 15923, the last base of the anticodon loop of the transfer RNA(thr) gene. The mutation lengthens the anticodon stem by added pairing and reduces the anticodon loop size from 7 to 5 nucleotides, potentially compromising transfer RNA(thr) function in translation and/or in processing the polycistronic RNA transcript. The patient's mother previously had a male infant who also died at 1.5 d postnatal, and both the mother and her twin have had multiple miscarriages. Amniocentesis for a genetic screen was performed on the mother's twin sister during a recent pregnancy; some of the cultured cells were made available for this study. The mutation was not found in the amniocytes or in umbilical cord blood obtained at birth; the baby was normal at birth and remains healthy. It is concluded that the mutation at nucleotide 15923 was most likely the cause of the fatal disease in the index case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511016 TI - Analysis of peroxisomes in lymphoblasts: Zellweger syndrome and a patient with a deletion in chromosome 7. AB - Lymphoblasts are useful cells for the diagnosis and basic studies of several human genetic disorders. Peroxisomal disorders are usually diagnosed by using fibroblasts or blood samples. Here, we report the characterization of peroxisomes in lymphoblasts. We demonstrated that lymphoblasts from a patient with Zellweger syndrome, the prototypical disorder of peroxisome biogenesis, contained peroxisomal ghosts like those described previously in Zellweger fibroblasts. We also found that lymphoblasts that carry a deletion on chromosome 7 (q11.23q22.1), a region thought to contain one Zellweger syndrome gene, contained normal peroxisomes. PMID- 8511017 TI - Practical methods to estimate whole body leucine oxidation in maple syrup urine disease. AB - We report the comparison of noninvasive methods to estimate whole body leucine oxidation in patients who have maple syrup urine disease. We used both an i.v. and an oral bolus of L-[1-13C]leucine and quantitated 13CO2 in expired air. Both methods differentiated patients with maple syrup urine disease from heterozygous and control subjects. Eight patients, whose disease differed in clinical severity, were selected for study and had a range of impaired values for whole body leucine oxidation. Six h after an i.v. bolus dose of L-[1-13C]-L-leucine, 13CO2 recoveries ranged from 0.8 to 19.7%. Three of the eight patients had significant increases in 13CO2 production after supraphysiologic thiamine therapy. After the oral dose of L-[1-13C]leucine, homozygous affected children produced less 13CO2 than normal, age-matched, childhood controls. In addition, the oxidation of orally administered L-[1-13C]leucine was reduced significantly in adult heterozygotes compared with adult controls. The proportion of whole body leucine oxidation by affected children was comparatively greater than that by their cultured cells, but cellular oxidation correlated significantly with whole body oxidation of leucine among affected patients. We conclude that these simplified analyses of whole body leucine oxidation define the degree of impaired branched-chain alpha-ketoacid dehydrogenase activity in patients with differing types of maple syrup urine disease and distinguish the subpopulation who might benefit from thiamine supplementation. PMID- 8511018 TI - Effect of maternal labor and mode of delivery on polymorphonuclear leukocyte function in healthy neonates. AB - In this study, effect of maternal labor and mode of delivery on polymorphonuclear leukocyte (PMN) chemiluminescence and random and chemotactic motility was evaluated in healthy full-term neonates. PMN were obtained from cord blood of three groups of neonates: group I, 24 vaginally delivered neonates; group II, 22 neonates delivered by elective cesarean section without labor; and group III, 18 neonates delivered by cesarean section after labor. In group III, six neonates were delivered by cesarean section for fetal distress with acidemia and 12 for failure of progression of labor. Peak chemiluminescence of PMN in group III was depressed compared with groups I and II (p < 0.01). There was no difference in the peak chemiluminescence of PMN from neonates in group I versus group II. Random motility of PMN in group III was increased compared with the random motility in groups I and II (p < 0.05). Chemotactic motility of PMN was comparable in all three groups. In group III, a negative correlation was noted between peak chemiluminescence of PMN and the duration of labor (p < 0.001), whereas no such correlation was observed in group I despite a similar duration of labor. There was no correlation between duration of labor and random and chemotactic motility of PMN in groups I and III. The results of this study indicate that labor and mode of delivery per se have no effect on PMN function and that factors other than labor such as fetal acidemia, fetal distress, arrested labor, or maternal administration of drugs may play a role in alteration of PMN function. PMID- 8511019 TI - Natural killer cytotoxicity and antibody-dependent cellular cytotoxicity of human immunodeficiency virus-infected cells by leukocytes from human neonates and adults. AB - In infants born to mothers infected with the human immunodeficiency virus (HIV), antibody-dependent cellular cytotoxicity (ADCC) or natural killer cytotoxicity (NKC) may either eliminate infection or ameliorate its course. We developed and standardized an assay for cytotoxicity of HIV-infected cells and studied the capacity of leukocytes from healthy neonates and adults to lyse HIV-infected cells by ADCC and NKC. The chosen target cell line, a T cell line infected with the HXB-2 clone of human T-cell lymphotrophic virus-IIIB, displayed stable surface expression of viral antigens over months of continuous culture and allowed simultaneous assessment of NKC and ADCC of effector cell populations. Conditions for optimal ADCC lysis of target cells were defined for unpurified peripheral blood mononuclear cells and purified lymphocytes and monocytes. Polymorphonuclear neutrophils from healthy adults and neonates exhibited low activity in ADCC of HIV-infected targets. Lymphocytes and monocytes from adults were found to differ in antibody dependence, kinetics, and sensitivity to latex inhibition for ADCC-mediated lysis of HIV-infected targets. Peripheral blood mononuclear cells of healthy neonates and adults displayed equivalent capacity to mediate NKC of HIV-infected targets. However, neonates' peripheral blood mononuclear cells were found to be significantly less active than adults' in ADCC lysis of HIV-infected cells. This pattern of diminished ADCC cytotoxicity with intact NKC is the opposite of that seen in HIV-infected adults. Our findings suggest that therapies designed to enhance ADCC effector cell function in the neonate may help interrupt vertical transmission of HIV. PMID- 8511020 TI - Transforming growth factor-alpha and epidermal growth factor expression in human fetal gastrointestinal tract. AB - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are mitogenic to the intestinal epithelium. To further clarify their role in the developing human fetal gut, their expression was studied in fetuses at 15 to 20 wk of gestation. TGF-alpha mRNA was present throughout the gastrointestinal tract, most abundantly in the duodenum. EGF mRNA could be detected only with ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. The effect of EGF and TGF-alpha on TGF-alpha mRNA expression was studied by culturing explants of fetal jejunum, ileum, and colon for 7 d in Leibowitz L-15 medium supplemented with 100 micrograms/L of either EGF or TGF alpha. EGF receptor-like immunoreactivity was detected in both the villi and the crypts. In the jejunum, exogenous EGF up-regulated TGF-alpha mRNA 3-fold. However, exogenous TGF-alpha reduced its own mRNA by 40%. No mature 6-kD TGF alpha was detected in the culture medium by Western blotting, but precursor forms of approximately 30 and 68 kD were present. The ileum and colon did not respond to either growth factor. Besides the gut, TGF-alpha was expressed in the gallbladder, salivary gland, adrenals, brain, kidney, liver, and placenta. The data imply an important role for TGF-alpha and EGF in the developing intestine. PMID- 8511021 TI - Total parenteral nutrition-associated alterations in hepatobiliary function and histology in rats: is light exposure a clue? AB - Light exposure of amino acids, especially in the presence of photosensitizers such as riboflavin, has been shown to result in photoproducts that are toxic both in vivo and in vitro. Provision of photooxidized single amino acids has been shown to result in hepatic dysfunction in both gerbils and rats. However, studies of the effects of light exposure of complete nutrient mixtures (glucose-amino acid-vitamins) on hepatobiliary responses are limited. These are important because, in clinical practice, total parenteral nutrition (TPN) solutions are continually exposed to light and because hepatic dysfunction is the most common metabolic aberration associated with TPN. Studies were conducted to compare the effects of TPN that had been exposed to light (+L) or protected from light (-L) on hepatobiliary function of rats. TPN solutions were either exposed to light or protected from light for 24 h and then infused into rats for 10 d. Data for enterally fed rats are also shown for comparison with parenterally fed animals. +L animals lost more weight and had lower bile flow, higher taurocholate output in bile, higher biliary osmolarity, and higher inorganic phosphate in bile. Hepatic histology demonstrated scattered foci of necrosis in eight of the eight +L animals and in only one of eight -L animals. These data demonstrate that protection of TPN solutions from light minimizes TPN-associated alterations in hepatobiliary function and histology. These histologic changes observed in the +L animals are in contrast to previous reports of TPN-induced histologic changes, suggesting a different mechanism. Our observations suggest that consideration be given to the implications of exposing TPN solutions to light. PMID- 8511022 TI - Induction of cytosolic phosphoenolpyruvate carboxykinase in the ovine fetal liver by chronic fetal hypoglycemia and hypoinsulinemia. AB - Fetal glucose production has been observed in the chronically hypoglycemic, hypoinsulinemic (HH) fetal lamb. The purpose of this study was to test the hypothesis that induction of hepatic gluconeogenic enzymes occurs in this condition. The activities of both mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase, and glucose-6-phosphatase, three key enzymes of gluconeogenesis, were determined in fetal sheep liver from HH lambs and controls (CONT). Pregnant ewes were maintained chronically hypoglycemic by continuous hyperinsulinemic clamps from approximately 80 d of gestational age (53% of gestation) for 6 wk. Fetuses (gestational age: HH = 136 +/- 2.6, CONT = 133 +/- 3.7 d) were maintained chronically hypoglycemic [HH = 0.51 +/- 0.05 versus CONT = 1.22 +/- 0.11 mmol/L (9.2 +/- 1.0 versus 21.9 +/- 11.9 mg/dL)] and hypoinsulinemic (HH = 3.3 +/- 0.6 versus CONT = 12.0 +/- 2.2 microU/mL) and delivered by cesarean section after measurement of fetal glucose production rate. Hepatic cytosolic PEPCK was 6.0 +/- 1.4 nmol/min/mg protein in CONT and 19.7 +/- 2.5 in HH lamb (p < 0.05), whereas mitochondrial PEPCK was not different between the two groups. Neither fructose-1,6-diphosphatase or glucose-6 phosphatase activities nor plasma glucagon levels were different between groups. These results suggest that chronic fetal hypoglycemia and hypoinsulinemia prematurely induce hepatic cytosolic PEPCK in the fetal lamb. The observed fetal glucose production in the HH fetal lamb may be due to gluconeogenesis. PMID- 8511023 TI - Correction of hyperinsulinemia by glyburide treatment in nondiabetic patients with thalassemia major. AB - Hyperinsulinemia and insulin resistance precede the development of diabetes in patients with thalassemia major on hypertransfusion/desferoxamine therapy. To examine whether these early metabolic defects could be reversed, seven nondiabetic patients with thalassemia (17 +/- 4 y) were studied for 12 mo before and during 12 mo of low-dose treatment with glyburide (1.25 to 3.75 mg/d), a second-generation oral hypoglycemic agent. Plasma glucose responses to oral glucose (1.75 g/kg body weight) were normal before and after glyburide. Plasma insulin responses were markedly increased before glyburide therapy (area under insulin response curve 86 +/- 15 and 96 +/- 15 versus 40 +/- 5 nmol/min/L in normal controls, p < 0.001). However, insulin responses to glucose fell significantly after 3 mo of glyburide (to 52 +/- 7 nmol/min/L, p < 0.05 versus pretreatment) and were normalized after 12 mo (42 +/- 7 nmol/min/L, p = NS versus controls). The rate of insulin-stimulated glucose metabolism during euglycemic insulin clamps (40 mU/m2/min) was low in the patients before treatment (163 +/- 10 versus 215 +/- 17 mg/m2/min in controls, p < 0.05) and increased to 205 +/- 30 mg/m2/min after 3 mo of glyburide. The treatment was well tolerated. In conclusion, in nondiabetic, hyperinsulinemic, thalassemic patients, chronic glyburide therapy normalizes insulin responses to oral glucose. To the extent that insulin hypersecretion contributes to the development of diabetes in thalassemia, glyburide therapy may provide a means of postponing this complication of the disease. PMID- 8511024 TI - Clinical characteristics and circulating collagen and laminin metabolites in insulin-dependent diabetic children with joint and skin manifestations. AB - One hundred seventy-four children and adolescents with insulin-dependent diabetes mellitus were examined for joint contractures and skin manifestations in their hands. Joint contractures were found in 52 (29.8%) and skin manifestations in 29 (16.6%) patients. To eliminate the possible confounding effects of age and duration of diabetes on the variables to be studied, patients younger than 7 y and with a duration of diabetes shorter than 3 y were excluded from the subsequent analyses. Of the remaining 108 children, those with joint contractures had lower serum concentrations of the 7-S domain of type IV collagen and the P1 fragment of laminin than the other patients (p = 0.033) but higher mean glycated Hb levels (p = 0.048). A clear association was noted between the occurrence of joint contractures and skin changes (p = 0.007). Background retinopathy was found in six patients (5.6%), three of whom had stage II joint contractures (p = 0.064). The children with skin changes and those with combined joint and skin manifestations more often had insulin-dependent diabetes mellitus in their first degree relatives (p = 0.038 and p = 0.043, respectively). No difference in relative height was found between the groups. No association could be seen between disease susceptibility antigens in the HLA-D locus and joint or skin manifestations. The lower levels of circulating collagen and laminin metabolites in the diabetic children with joint contractures suggest that these patients are characterized by a reduced turnover of basement membranes in tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511025 TI - Changes of plasma lipids and erythrocyte membrane fluidity in psoriatic children. AB - Psoriasis has been associated with an abnormal plasma lipid metabolism, and changes of erythrocyte membrane lipid composition and fluidity have been shown in adult patients. To investigate whether the alterations of plasma lipids appear also in pediatric patients, we have studied plasma lipids and lipoproteins in 15 prepubertal children affected by mild-to-moderate psoriasis with respect to healthy controls. The patients showed higher levels of plasma total cholesterol (4.44 +/- 0.78 versus 4.03 +/- 0.58 mmol/L), a significant increase of cholesterol associated with HDL (1.39 +/- 0.26 versus 1.13 +/- 0.28 mmol/L, p = 0.02), and a significant decrease of the ratio LDL cholesterol to HDL cholesterol (1.73 +/- 0.6 versus 2.46 +/- 0.8, p = 0.02). By using fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, we have shown a significant increase in fluidity in erythrocyte membrane of psoriatic children that was associated with a slight, but not significant, decrease in the cholesterol to protein ratio (422 +/ 127 versus 503 +/- 117 nmol/mg). No significant changes of phospholipid fatty acid composition have been shown, in disagreement with previous studies in adult patients. Our results support the relation between childhood psoriasis and plasma lipid changes, which are likely related to the slight compositional changes in erythrocytes. However, the observed abnormalities are expressed differently in children than in adults. PMID- 8511026 TI - Reduced inhibin and elevated gonadotropin levels in early pubertal boys with testicular defects. AB - In the prepubertal quiescent period, the control of gonadotropin secretion is assumed to be mediated by neuroendocrine inhibitory mechanisms, whereas little or no effect is thought to be mediated by the gonad. However, in pubertal-aged children with primary gonadal failure, gonadotropins increase to supranormal levels, suggesting that gonadal factors become more important in the control of gonadotropin secretion at that age. These gonadal factors have been poorly characterized so far. To clarify the relationship of inhibin and testosterone to the control of gonadotropin secretion during sexual maturation, we examined serum inhibin, testosterone, LH, and FSH concentrations in 10 boys with testicular defects and in nine healthy boys, in prepuberty and in early puberty. Serum was obtained at 15-min intervals for at least 6 h during the night. Prepubertal-aged boys with testicular defects had only slightly higher FSH levels than healthy boys, and their LH and inhibin levels were no different. In contrast, pubertal aged boys with testicular defects had higher LH and FSH levels and lower inhibin levels than healthy boys. In prepubertal-aged boys, no correlation was found between individual mean inhibin level and mean FSH or LH level. In contrast, in pubertal-aged boys, an inverse nonlinear relationship between mean inhibin level and mean FSH and LH level was seen. The inverse value for inhibin correlated with FSH (r = 0.74, p < 0.01) and with LH (r = 0.81, p < 0.01). In conclusion, our results suggest that inhibin is a factor involved in the control of gonadotropin secretion in boys, at least in the pubertal period. PMID- 8511027 TI - Developmental differences in catalase activity and hypoxic-hyperoxic effects on fluid balance in isolated lamb lungs. AB - The effects of hypoxia (95% N2/5% CO2) followed by hyperoxia (95% O2/5% CO2) were determined in isolated lungs of premature (gestational age 128 to 135 d) and full term (postnatal age 0 to 5 d) lambs perfused with autologous blood (100 mL.min 1.kg body weight-1). In full-term lungs, hypoxia-hyperoxia compared with hypoxia alone decreased pulmonary artery pressure and increased weight gain and extravascular lung water. In premature lungs, the increase in weight gain was greater and was associated with hemorrhage and increased pulmonary arterial and peak airway pressures. Papaverine eliminated reoxygenation-induced differences in pulmonary artery pressure, peak airway pressure, and weight gain in both age groups. Osmotic reflection coefficients for total protein and albumin, measured by a modification of the filtered volume technique, averaged 0.591 +/- 0.054 (SEM) and 0.465 +/- 0.054 (SEM), respectively, and were not altered by reoxygenation or age. Catalase activity in lung tissue and erythrocytes was lower in premature lambs, but there were no age-related differences in superoxide dismutase or glutathione peroxidase activities. These results demonstrate that hypoxia-hyperoxia in isolated lamb lungs increased lung weight due to edema formation in full-term lamb lungs and hemorrhage in premature lamb lungs and that this increase was greater in premature lamb lungs. We speculate that the weight gain caused by reoxygenation was due to a vasodilation-induced increase in surface area in full-term lamb lungs and a vasoconstriction-induced increase in vascular pressure in premature lamb lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511028 TI - Effect of growth and maturation in a hypoxic environment on maximum coronary flow rates of isolated rabbit hearts. AB - This study was designed to determine the effect of growth and maturation of rabbits in a hypoxic (H) environment on the ability to perfuse myocardium. Rabbits were raised in either a normoxic (N) (PO2 = 19.7 kPa or 149 torr) or an H environment (PO2 = 8.6 kPa or 65 +/- 3 mm Hg) and were studied at ages 5 wk (immature) and 12 wk (mature). Coronary flow (CF) was measured at baseline, during infusion of a maximally dilating concentration of adenosine (A), and at peak reactive hyperemic response to transient inflow occlusion in an isolated, non-blood-perfused heart preparation. Hearts were unloaded, paced at a constant rate (200 beats/min), and perfused at a constant inflow pressure (50 mm Hg). Regional CF was measured, using microspheres, in right ventricular, left ventricular, and atrial cardiac segments during vasodilation with A. H rabbits developed right ventricular but not left ventricular segment hypertrophy/hyperplasia. CF was greater in immature than mature hearts and higher in H than N hearts during baseline, vasodilation with A, and at peak reactive hyperemia (two-way analysis of variance, p < or = 0.05). Regional CF during vasodilation with A was greater in immature than mature hearts, in both right and left ventricular segments, and higher in H than N hearts in all cardiac segments (two-way analysis of variance, p < or = 0.05). Differences in total and regional CF between H and N hearts were present at both study ages (t test, p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511029 TI - Role of adenosine triphosphate and adenosine in oxygen-induced pulmonary vasodilation in fetal lambs. AB - We investigated the hypothesis that purine nucleotides, ATP and adenosine, mediate the pulmonary vasodilation that occurs at birth in response to an increase in arterial O2 pressure (PaO2). We studied 20 fetal lambs 1 to 3 d after placement of intravascular catheters and a flow transducer around left pulmonary artery. In 16 lambs, we investigated the effects of 1) an increase in fetal PaO2 on ATP levels in pulmonary circulation and 2) 8-phenyl-theophylline (8-PT) and cibacron blue, antagonists of receptors for adenosine and ATP, on pulmonary vasodilation caused by increased PaO2. In four other lambs, we investigated the specificity of 8-PT and cibacron blue for purine receptors by investigating their effects on pulmonary vasodilation caused by acetylcholine, bradykinin, and nitroprusside. The fetal PaO2 increased by 7 +/- 2 during administration of 100% O2 to the pregnant ewe, resulting in a 3-fold decrease in PVR and increase in pulmonary blood flow. Blood and plasma concentrations of ATP in fetal pulmonary artery and left atrium increased significantly during the increase in fetal PaO2. 8-PT and cibacron blue caused increases in baseline pulmonary and systemic vascular pressures and pulmonary vascular resistance and inhibited the pulmonary vasodilation caused by O2. 8-PT and cibacron blue did not alter the pulmonary vascular effects of acetylcholine, bradykinin, and nitroprusside. An increase in baseline pulmonary vascular resistance caused by infusion of U46619 (in four lambs) did not alter the pulmonary vasodilation caused by O2. In summary, O2 induced pulmonary vasodilation is accompanied by increased ATP levels in pulmonary circulation and is attenuated by antagonists of purine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511030 TI - A unique pattern of coagulation abnormalities in carbohydrate-deficient glycoprotein syndrome. AB - The carbohydrate-deficient glycoprotein syndromes are a recently individualized group of genetic multisystemic disorders. A predominant feature is a severe involvement of the central and peripheral nervous system resulting in psychomotor retardation, seizures, ataxia, and, mostly after infancy, stroke-like episodes. The hallmark biochemical feature is a carbohydrate deficiency in a large number of serum glycoproteins. Because coagulation factors and inhibitors are also glycoproteins, we performed a systematic study of these factors and inhibitors in nine patients with carbohydrate-deficient glycoprotein syndrome. All showed a decreased activity of factor XI and of the coagulation inhibitors antithrombin III and protein C. In five of seven patients more than 1 y old, there was also a (less pronounced) decrease of protein S and of heparin cofactor II. This combined coagulation inhibitor deficiency could explain the stroke-like episodes occurring in these children. PMID- 8511031 TI - Bone marrow scintigraphy in myelofibrosis. AB - Seventy-seven patients with myelo-fibrosis have been studied during the last three years, by using as tracers 99m Tc- colloids and 111 In-transferrin. A low axial uptake of the colloids, an extension of the indium uptake beyond the axis towards the knees and sometimes ankles and elbows, the splenic indium uptake, are valuable diagnostic criteria, particularly useful for excluding a myelo-fibrosis associated to a malignant disorder. The clinical severity of the disease may be predicted from isotopic studies, particularly the disappearance of a physiologically active bone marrow (indium uptake). The bone marrow scintigraphy could contribute to the difficult decision of splenectomy. PMID- 8511032 TI - Improvement of cytogenetic results in B-cell chronic lymphocytic leukemia using immuno-purified leukemic cells. AB - Cytogenetics of purified B lymphocytes and whole blood cultures were studied in 14 patients with B-CLL and fluorescence in situ hybridization (FISH) was performed on interphase cells in 12 of these cases in order to detect trisomy 12. Only one minor abnormal clone was found on whole blood cell cultures, clonal anomalies were found in a large proportion of mitoses of 6/14 cultures of purified B cells. FISH detected a trisomy 12 in a case, not found in whole blood cultures but found in 78% metaphases of cultures of purified B lymphocyte. This method may be as sensitive as FISH for the detection of trisomy 12 and improves the detection of clonal abnormalities in CLL. PMID- 8511033 TI - Recent advances in B cell acute lymphoblastic leukemia (Burkitt leukemia) therapy in childhood. AB - Acute lymphoblastic leukemia with Burkitt type cells has been described in 1975. Until the mid-1980, with conventional treatments, the prognosis was very poor with very few long-term survivors. Failures were mainly due to central nervous system involvement at diagnosis or relapse. After that period a dramatic improvement has been observed with intensified treatments based on Burkitt's lymphoma therapy regimens. High-dose cyclophosphamide, high-dose methotrexate, high-dose ara-C in compact protocols completed in 6-7 months have been proven useful. 75% of the patients can be cured. PMID- 8511034 TI - [Comparison between intensive consolidation by bone marrow autograft or by chemotherapy of acute myeloblastic leukemias in 1st complete remission: AML8A protocol of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC)]. PMID- 8511035 TI - Molecular and cellular biology of antigen presentation. PMID- 8511036 TI - Ataxia telangiectasia: a model for T-cell leukemogenesis. AB - Ataxia telangiectasia is a complex genetic disease which includes a high risk to develop lymphoid malignancies. In approximately 10% of the patients, clonal translocations are observed in large T lymphocytes populations, with generally no consequences for the patient. Cytological and biological studies of these cell populations have shown striking similarities with T-cell prolymphocytic leukemia. Clonal chromosomal aberrations are constituted by the translocation of one TCR gene to either the 14q32.1 band or the Xq28 band. Whereas no gene candidate is yet identified on the 14q32.1 region, we have recently identified a new gene on Xq28 that may play a role in leukemogenesis. PMID- 8511037 TI - Intensive care for patients with malignant hematologic diseases. PMID- 8511038 TI - Germline mutations of the p53 tumor-suppressor gene in cancer-prone families: a review. AB - Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast carcinoma, soft tissue sarcoma, osteosarcoma, leukemia and adrenocortical carcinoma. These diverse tumor types develop at unusually early ages. Analysis of the tumor suppressor gene p53 in family members with LFS have demonstrated that germline mutations in the p53 gene were present in most of the LFS family tested so far. Furthermore, germline p53 mutations were also found in cancer-prone individuals which were not indicative of the LFS. PMID- 8511039 TI - Some recent aspects of the molecular biology of human lymphoma. AB - Some recent aspects of the molecular biology of chromosome abnormalities that activate the BCL2 gene in B cell malignancies (follicular lymphoma, chronic lymphocytic leukemia) are discussed. We also report data showing that the Epstein Barr virus (EBV) LMP-1 protein which can induce the expression of BCL2, is found infrequently in follicular lymphomas which exhibit no apparent BCL2 gene rearrangement. PMID- 8511041 TI - Fluorescence in situ hybridization and cytogenetics of hemopoietic malignancies: new developments. AB - Fluorescence in situ hybridization (FISH) is currently developed to analyse chromosomal abnormalities of hemopoietic malignancies in several ways: description of chromosomal rearrangements using specific probes or chromosome painting; delineation of chromosomal breakpoints with probes previously localized to chromosomal bands; hybridization to interphase nuclei to detect numerical changes and, now, some structural abnormalities. Examples of usefulness of FISH to study hemopoietic malignancies are given. PMID- 8511040 TI - A possible role for the Ras-related Rab2 protein in the immunological events associated with hematological malignancies. AB - The Rab branch of the Ras-related guanine nucleotide (GTP/GDP)-binding proteins currently includes at least thirty related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. We have demonstrated the overexpression of the Rab2 protein in peripheral blood mononuclear cells from patients exhibiting Sezary syndromes and other lymphoid and myeloid malignancies. Several lines of evidence suggest that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provide strong evidences for the implication of a small GDP/GTP binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined. PMID- 8511042 TI - History of promyelocytic leukemias. AB - History of a constant fight against dogmas, dogma refusing the promyelocyte existence, refusing acute promyelocyte leukemia existence, (first descriptions in Norway and in France in 1957), refusing remission, refusing complete cure (first complete cure with anthracyclins), accepting only destructive treatments. Franco chinese works developed by Wang, Laurent Degos and their co-workers have proved the differentiation mechanism of remission due to the consequences of this important discovery. Acute promyelocytic leukemia, a model for other leukemias for cancers. PMID- 8511043 TI - Platelet activation in thrombotic disorders. AB - Recent advances have resulted in the elucidation of the principal molecular pathways of platelet function. Parallel studies have led to the identification of glycoprotein antigens whose presence at the platelet surface indicates an activated state. Such markers include GMP-140 and other glycoproteins of intracellular membranes whose translocation requires secretion and fusion of granule membranes with those joined to the surface. Other markers include activation-dependent epitopes on the GP IIb-IIIa complex and adhesive proteins bound to the activated GP IIb-IIIa receptor. Such epitopes can be detected by specific monoclonal antibodies. Quantification of their binding by flow cytometry allows an estimation of epitope expression within the whole platelet population. Our studies are designed to answer the question of whether measuring these epitopes is useful for predicting thrombosis in patients with acute cardiovascular disease. For this, we have examined three states where platelet function may be modified and where the risk of thrombosis and/or bleeding is increased. These include (i) patients with severe burns, (ii) patients who have undergone coronary angioplasty, and (iii) patients receiving fibrinolytic therapy following myocardial infarction. Our results show that activated platelets can be detected in the circulation and that their level reflects the degree of the lesion. Nonetheless, we have as yet failed to show a direct correlation between their presence and a future pathological event. PMID- 8511044 TI - Mycosis fungoides and the Sezary syndrome. PMID- 8511045 TI - Aspergillosis: advances in immunological diagnosis and therapeutic measures. AB - Invasive aspergillosis has become the most frequent cause of death due to opportunistic infections in hematological units where neutropenic patients and bone marrow transplant patients are treated. This is largely a consequence of the difficulty of establishing an early clinical or microbiological diagnosis, and the ensuing delay in starting antifungal therapy. Furthermore, the more effective treatment is not really codified. In this article, we make a review of advances in immunological diagnosis and in therapy against invasive aspergillosis for the last years. PMID- 8511046 TI - Aplastic anemia associated with "bird-headed" dwarfism (Seckel syndrome). AB - The Seckel syndrome or "bird-headed" dwarfism associates a severe short stature, mental deficiency and various malformations with characteristic facial appearance. It has been described in these children a moderate or severe marrow hypoplasia. The aplasia is unlikely constitutional and different from the Fanconi disease hypoplasia. We report here 2 cases of a such association. One of them had been cured by bone marrow transplantation. PMID- 8511048 TI - Inquiring minds. PMID- 8511047 TI - Badlands. PMID- 8511049 TI - Silencing nurses. PMID- 8511050 TI - Fatal attraction. PMID- 8511051 TI - Raising a voice. Interview by Phil Cohen. PMID- 8511052 TI - The rushed revolution. PMID- 8511054 TI - Mind Your Back. Reporting back. PMID- 8511053 TI - Short rations. PMID- 8511055 TI - Mind Your Back. The last straw. PMID- 8511056 TI - Arthritis: tackling pain. PMID- 8511057 TI - Making sense of blood groups. PMID- 8511058 TI - Professional development. Who cares? PMID- 8511059 TI - Alcohol misuse--living with a timebomb. PMID- 8511060 TI - Her story. PMID- 8511062 TI - Complementary medicine--chiropractic. PMID- 8511061 TI - Education--that thinking feeling. PMID- 8511063 TI - Learning disabilities--diverse options. PMID- 8511064 TI - Learning disabilities--keeping it in the family? PMID- 8511065 TI - Learning disabilities--tailor-made for the job. PMID- 8511066 TI - Learning disabilities--consensus or confusion? PMID- 8511067 TI - [Cancer of the breast in men. 106 cases]. AB - In a retrospective and multicentre study 106 cases treated from 1970 to 1985 were analysed. The patients' median age was 64 years. TNM classification showed 20 T1, 48 T2, 2 T3, 32 T4 and 4 Tx. Twenty one patients had clinical gynaecomastia; 99 underwent surgery and 85 radiotherapy; 32 received adjuvant chemotherapy or hormonal therapy. The main histological type was ductal infiltrating carcinoma; 82 axillary dissections were performed, and positive lymph nodes were found in 67 percent of the cases. Hormone receptors were positive in 15 out of 20 measured cases. Five and 10 years overall survival rates (Kaplan-Meier) were 57 and 37 percent, and corrected survival rates 68 and 55 percent respectively. The main prognostic factor remains the clinical size of the tumour (T) and histologically axillary node status (pN). Eleven patients developed a second metachronous cancer. The aetiology of male breast cancer is a poorly known as that of female breast cancer. Nevertheless, imbalance among oestrogens and androgens due to metabolic, infectious or pharmacological causes is probably responsible, at least in part, for this cancer. An on-going multicentre prospective national trial tries to address this question. PMID- 8511068 TI - [Acquired autoantibodies directed against human factor VIIIc. Treatment of 2 hemorrhagic accidents with porcine factor VIIIc]. AB - The emergence of an autoantibody directed against factor VIII may be responsible for severe, life-threatening haemorrhages. This rare disease is usually idiopathic, but it may be consecutive to an autoimmune disease or to the absorption of certain drugs such as penicillin. The diagnosis rests on the finding of a prolonged activated thromboplastin time with presence of a circulating anticoagulant and deep fall in factor VIII level. Two cases of severe haemorrhage successfully treated with porcine factor VIIIc are reported. The first case concerned an 80-year old woman presenting with a large haematoma of the thigh uncontrolled by injections of human factor VIIIc. The second case was that of a 24-year old woman in a state of shock due to a pleural blood effusion that occurred during heparin treatment of cerebral thrombophlebitis, combined with penicillin treatment of bronchial superinfection. In both cases the high titer autoantibody to the human factor VIIIc did not, or little, cross with porcine factor VIIIc. Factor VIII rose after the first injection of the porcine factor, and the haemorrhage was rapidly controlled. In both cases, the autoantibody disappeared within a few months, either spontaneously or after treatment with immunosuppressants. PMID- 8511069 TI - [Viral infections and asthma]. AB - Respiratory tract viruses have been held responsible for the genesis and aggravation of asthma in both children and adults. The relationship between asthma and viruses is looser in adults than in children, but it has been demonstrated that viral infections can generate a peripheral obstructive disorder on the one hand, and a transient non-specific bronchial hyperreactivity in healthy subjects on the other hand. Current data are insufficient to define clearly the alterations induced by viral infections and responsible for bronchial inflammation and non-specific bronchial hyperreactivity. Numerous studies have concluded to a complex mechanism involving bronchial epithelium lesions, imbalance of the autonomic nervous system in bronchial tone regulation, occurrence of immediate hypersensitivity reaction with facilitation of its delayed component, and cytokines produced during viral infection. PMID- 8511070 TI - [Diagnosis of a pelvic mass with elevation of CA 125 after liver transplantation]. PMID- 8511071 TI - [Chemoprophylaxis of malaria by doxycycline in Cambodia]. PMID- 8511072 TI - [Liver abscess revealing listeriosis]. PMID- 8511073 TI - [Comparison of two methods of evaluation of dietary calcium intake]. PMID- 8511074 TI - [Purpura revealing convulsive crisis]. PMID- 8511076 TI - [Corticoids, a debated adjuvant for the treatment of bacterial meningitis]. PMID- 8511075 TI - [Toxic dermatitis induced by bamifylline. 2 cases]. PMID- 8511077 TI - [Resectable liver metastases and synchronous extra-hepatic sites of colorectal origin. Surgical indications]. AB - Twenty-two patients with liver metastases and synchronous extra-hepatic localizations or colorectal cancer underwent complete resection of all their cancerous lesion. Their survival was not significantly different from that of 87 patients in whom single or multiple metastases involving only the liver had been resected. Analysis of our 22 patients showed that they fell into two subgroups: those with lung metastases (n = 5) and those with pediculate colonic nodes (n = 6), who benefited from the double resection since their disease-free survival rate at 5 years was 35 percent. In contrast, patients who had a few peritoneal nodules (n = 8) relapsed during the first 13 postoperative months. The presence of one or a few extra-hepatic lesions does not necessarily preclude resection of the liver metastases, provided they can be resected during the same operation in case of intra-abdominal lesions and during a later operation in case of lung metastases. A single peritoneal nodule may be the first manifestation of peritoneal dissemination and contra-indicates the resection of liver metastases. PMID- 8511078 TI - [Gallium-67 scintigraphy in malignant lymphoma]. AB - The presence of a residual mass is a frequent and difficult problem in the treatment of Hodgkin's or non-Hodgkin's lymphoma: since it is of major importance to determine whether the lesion is a fibrous mass or a still progressing tumour requiring additional therapy. Gallium-67 scanning, performed in a series of 52 patients, provides an answer to this question since there is an excellent correlation between gallium uptake by the tumoral masses and their progressiveness. Magnetic resonance imaging was carried out in half of our patients: the finding of a low-intensity signal on T2-weighted sequences proved that the residual mass was fibrous, whereas a high-intensity signal on T2 weighted sequences did not distinguish between fibrous and tumour masses. The priceless information provided by the simple and non invasive method that is gallium scanning is extremely useful to evaluate the extension of lymphomas and to determine whether residual masses are tumoral or fibrous. PMID- 8511079 TI - [Rochalimaea henselae infection. Febrile pancytopenia and hepatic peliosis in a patient with HIV infection]. AB - A case of Rochalimaea henselae infection in an AIDS patient is reported. The R. henselae infection was revealed by febrile pancytopenia associated with liver and spleen enlargement. The diagnosis was made on the finding at histology of hepatic peliosis lesions. Within these lesions Warthin Starry staining displayed bacilli that were identified as R. henselae. This case shows that all HIV-infected patients with these symptoms might be infected with this organism. PMID- 8511080 TI - [Dissection of the Calot's triangle by the celioscopic approach]. AB - Laparoscopy seems to increase the frequency of post-cholecystectomy biliary complications. Irrespective of the instruments and techniques utilized, dissection of Calot's triangle must be performed in compliance with the classical rules of bile duct surgery. These rules are: always keep in contact with the gallbladder; completely dissect the Calot's triangle area which must not contain more than one biliary tract element; never dissect the cystic duct beyond the right border of the hepatic choledochus; never section an element that is not identified with certainty; systematically perform a peroperative transcystic cholangiography, in particular to detect the anatomical variants of the extra hepatic biliary ducts. PMID- 8511081 TI - [Lung transplantation. Contraindications and new indications]. AB - The authors review the recent changes observed in the indications for lung transplantation. Several classical contra-indications have been alleviated or even cancelled. Chronic infection presenting as cystic fibrosis has become one of the first indications for lung replacement. Respirator-dependent patients are at an operative risk comparable to the overall results. Long-term corticosteroid therapy and pleural adhesions are no longer formal contraindications but should be approached with extreme caution. In recent years, single lung transplantation has been extended to diseases, such as emphysema and pulmonary hypertension, which were formerly indications for double-lung or heart-lung transplantation. The reasons for this include donor shortage and the better 1-year survival following single lung transplantation. The most recent development is paediatric lung transplantation. The legitimacy of redo transplantation is controversial. PMID- 8511082 TI - [Reactions to iodine contrast media]. AB - Contrast media are used in many radiological examinations, but they are responsible for 4.6 to 8.5 percent of the toxic or anaphylactoid adverse reactions observed. The early contrast media were hyperosmolar, whereas those in current use are isosmolar and either ionic or non-ionic. The patient's age, the presence of a pre-existing disease and a history of adverse reactions to contrast media are the most important risk factors. Seventeen to 35 percent of these reactions recur. Several physiopathological mechanisms have been blamed for adverse reactions to contrast media, including complement activation, histamine release, recruitment of inflammation mediators, and antigen-antibody reaction. There is no paraclinical examination that can diagnose or predict such reactions. Various preventive tests have been studied and applied to individuals with or without history of reaction. In a population of patients with previous reaction, the administration of corticosteroids 12 h and 2 h before the radiological examination resulted in a significant reduction of the number of reactions. In patients at risk (i.e. those with previous reactions of this kind) the results varied, but in these 2 groups of subjects non-ionic products given either alone or with corticosteroids or H1-antihistaminics reduced to 1 percent the incidence of reactions. So far, tachyphylaxis has virtually played no role compared with these preventive treatments. It is concluded that patients with a history of anaphylactoid reactions who must receive another injection of contrast medium, a non-ionic product and/or the H1-antihistaminic-corticosteroid combination should be used. PMID- 8511083 TI - [Addiction to zipeprol]. PMID- 8511084 TI - [Prevotellia bivia responsible of Lemierre syndrome]. PMID- 8511085 TI - [Anaphylactic shock during an ovulation induction treatment by pulsatile infusion of LHRH]. PMID- 8511086 TI - [Atypical form of Miller Fisher syndrome]. PMID- 8511087 TI - [Atypical malignant melanoma in a HIV-positive patient. A fortuitous association?]. PMID- 8511088 TI - [Bradycardia and hypothermia in an elderly patient receiving fluoxetine]. PMID- 8511089 TI - [Bronchospasm of allergic mechanism caused by pentamidine isethionate aerosols]. PMID- 8511090 TI - [Cortical blindness disclosing progressive multifocal leukoencephalitis in AIDS]. PMID- 8511091 TI - [Pre-exposure rabies immunization in occupational exposed milieu. A 5-year prospective and comparative study of immunogenicity]. AB - Pre-exposure rabies immunization has been the object of numerous immunogenicity studies with cultivated cell vaccines. Several primary immunizations and booster injection schedules have been suggested. The purpose of the present study was to compare simultaneously the immunogenicities of two vaccines at 5 years and those of two primary immunization schedules with a booster injection at 1 year. We compared the vaccine prepared from Vero cell cultures (PVRV) versus the reference vaccine prepared from human diploid cell culture (HDCV). We also compared primary immunization with 2 injections (on days 0 and 28) versus 3 injections (on days 0, 7 and 28). This phase IV study was prospective, randomized and conducted on open cohorts, according to a factorial plan defining four modalities (HDCV 2, HDCV 3, PVRV 2, PVRV 3). The study involved 312 volunteers of both sexes, aged from 15 to 65 years and exposed to rabies by their profession. The vaccines were injected intramuscularly in the deltoid region. Immunogenicity was evaluated by staged titering of neutralizing antibodies, using immunofluorescence. Seroprotection levels and mean geometrical means of titers were compared. The 3 injections schedule proved to be significantly superior to the 2 injections schedule. No difference could be clearly elicited between the two vaccines. The worst results were obtained with PVRV 2, with a 68.3 percent seroprotection rate at five years; with the other modalities this rate was 93.1 percent or more. We therefore recommend the following procedure: primary immunization by 3 injections, with a booster dose at 1 year, particularly when PVRV is used. It seems that the seroprotection obtained in this manner would make it possible to envisage a booster injection every 5 years. PMID- 8511092 TI - [Congenital C1-esterase inhibitor deficiency. A study of 4 Algerian families]. AB - We present the results of a preliminary study (the first of this kind in Algeria) in which 4 families presenting with congenital deficiency of the C1-esterase inhibitor (C1-INH) responsible for hereditary angioneurotic oedema were biologically explored. The complement fractions C1-INH, C4 and C3d were assayed in 38 subjects of the 4 families. Extending this biological evaluation to all members of theses families enabled us to identify all asymptomatic subjects (46 percent in our series). In 2 patients the congenital disease was associated with systemic lupus erythematosus. Some clinico-biological discordances are reported and discussed in the light of data from the literature. PMID- 8511093 TI - [Malignant germinal tumors of the thyroid. 2 cases]. AB - Malignant germinal tumours of the thyroid gland are exceptional. Two cases are reported here. The first case concerned an 8-year old girl who had a teratoma; she was treated by surgery and adjuvant chemotherapy; 4 years after the diagnosis she is still alive and in complete remission. The second case is that of a 21 year old woman with a vitelline sac tumour treated by surgery and radiotherapy; she soon had lung metastases and died. The diagnostic, prognostic and therapeutic aspects of malignant germinal tumours of the thyroid gland are presented, together with data from a review of the literature. The authors insist on the importance of marker assays for all thyroid tumours with suspicious cytology. These tumours should be treated by surgery and initial chemotherapy combined, just as malignant germinal tumours located in other organs. PMID- 8511094 TI - [Imaging of pigmented villonodular synovitis]. AB - Pigmented villonodular synovitis is a rare disease which is usually benign but sometimes causes wide articular destruction. Since its clinical signs and symptoms are not specific, the disease may remain undiagnosed, sometimes for long periods. The diagnosis is generally confirmed at pathology, but it can now be strongly suggested by modern imaging methods. Standard radiography may be normal, with a variety of images. Arthrography with an opaque material points to the diagnosis in only two-third of the cases. Ultrasonography is non-specific. Computed tomography may be strongly suggestive of pigmented villonodular synovitis in cases with high density synovia; when coupled with arthrography, it provides detailed information on lesions of the cartilage and on extension of the synovial process. The most sensitive and specific method is magnetic resonance imaging, the most characteristic sign being low-intensity signal areas on T1- and T2-weighted sequences, corresponding to haemosiderin-loaded nodules. Performed after standard radiography, magnetic resonance imaging is the best examination method for the diagnosis and pretherapeutic evaluation of suspected villonodular synovitis. PMID- 8511095 TI - [Tuberculosis: a still current present cause of scleritis]. PMID- 8511096 TI - [Aseptic meningitis during pyrazinamide therapy for lupus erythematosus]. PMID- 8511097 TI - [Palinacousis related to right temporo-parietal hemorrhage]. PMID- 8511098 TI - [Value of acetate medroxyprogesterone in the treatment of cachexia in AIDS]. PMID- 8511099 TI - [Brachial plexus involvement disclosing systemic lupus erythematosus]. PMID- 8511100 TI - [Encephalitis in infectious mononucleosis]. PMID- 8511101 TI - [Specialized memory consultation. Value and evaluation after 2 years of functioning]. AB - Disorders of memory are a frequent cause of consultation and are observed in dementias, in some depressive syndromes and in normal ageing. The specialized memory consultation is based on two successive examinations: one by a neurologist, the other by a psychologist, using standardized batteries of tests. In 100 consecutive subjects, 3 main groups of about 20 to 30 individuals each could be identified: dementia syndromes, psychiatric disorders and age-related disorders of memory. The remaining subjects had various diseases. In subjects with memory complaints a psychometric evaluation performed by a team of specialists seems to be the only means of refining the diagnosis enough for a personalized management. In addition, the specialized consultation team acquires the knowledge that will help it, in the future, to lay down the bases of medical prevention of pathological cerebral ageing. PMID- 8511102 TI - [Proximal tubal obstruction. Treatment by recanalization and transcervical dilatation]. AB - Forty-three fluoroscopic transcervical fallopian tube recanalizations were performed in 30 consecutive patients whose infertility was due to proximal tubal obstruction demonstrated by hysterosalpingography and laparoscopy. All had been recommended tubal microsurgery or in vitro fertilization. Thirty fallopian tubes (81 percent) were successfully recanalized, with balloon dilatation in 20 (57 percent). Six intrauterine and one ectopic pregnancies resulted from successful tuboplasty. Six women who did not conceive underwent follow-up hysterosalpingography 6 months on average after tuboplasty; 2 were found to have tubal reocclusion. There was no difference in our results between patients simply recanalized and those in whom recanalization was combined with balloon dilatation. We conclude that transcervical balloon tuboplasty is an effective treatment of infertility caused by proximal tubal obstruction. PMID- 8511103 TI - [Health personnel and viral hepatitis. Risk and prevention]. AB - Health care workers are exposed to the risk of viral hepatitis. There has recently been a shift in epidemiology from hepatitis B to hepatitis A, and these subjects are less and less spontaneously immunized before entering their profession; vaccination, therefore, should benefit them. Concerning hepatitis B, vaccination has made a huge impact and considerably reduced the number of occupational cases. The occupational risk for hepatitis C virus infection seems to be much lower than the risk for hepatitis B. PMID- 8511104 TI - [Cutaneous metastases of internal cancers]. AB - Cutaneous metastases from internal tumours are relatively rare, appearing in ca. 4.5 percent of the cases, but their recognition is important; indeed, even though they usually appear during a known neoplastic disease, they may be the presenting sign of a hitherto unknown tumour. They may also constitute the first manifestation of relapse of a tumour considered to be in complete remission. Cutaneous metastases generally manifest as solitary or multiple nodules devoid of specific clinical features, over the head, chest and abdominal wall. They are mainly due to cancers of mammary origin in women, or of pulmonary, renal and gastrointestinal origin in men. Any histological type may be encountered, with a predominance of adenocarcinomas. The histological aspect often does not allow recognition of the primary site, which can be identified in selected cases by immunohistochemical studies. Although long survivals have exceptionally been observed after the development of cutaneous metastases, their occurrence usually has an ominous prognostic significance and considerably reduces the chances for an efficient treatment. PMID- 8511106 TI - [Remission of autoimmune thrombopenic purpura after low-dose splenic irradiation]. PMID- 8511105 TI - [Occurrence of gastric phytobezoar after chemotherapy with vinorelbine]. PMID- 8511107 TI - [Pituitary adenoma with presence of lymphocytic infiltrate]. PMID- 8511108 TI - [Pleurisy complicating pseudomembranous colitis]. PMID- 8511109 TI - [Compression of the conus medullaris caused by osteoporotic collapse of the 1st lumbar vertebra, associated with arachnoid cyst]. PMID- 8511110 TI - [Internal pericecal hernia]. PMID- 8511111 TI - [Towards a selective immunotherapy of rheumatoid polyarthritis]. PMID- 8511112 TI - [Esophageal prostheses in cancer stenosis. Insertion with the Dumon-Gilliard device. 342 patients]. AB - Endoscopic placement of an oesophageal prosthesis rapidly brings a satisfactory comfort to patients with cancer of the oesophagus beyond the therapeutic stage. When the least traumatic technique and materiel are used, the procedure is simple and safe, irrespective of the patient's general condition and the extent of local or regional lesions. The present possibility to insert, at the same time, a tracheobronchial prosthesis broadens the indication to patients who have an oesophagus-airway fistula or who suffer from compression of the trachea or the left bronchus. The procedure is performed under general anaesthesia at the expense of a short hospital stay which is always appreciated by this type of patients. The author's 10-year experience of oesophageal prosthesis placement with the Dumon-Gilliard applicator, is reported. PMID- 8511113 TI - [Phosphocalcium metabolism in patients with calcified valvular bioprosthesis]. AB - Calcium and gla-protein content are increased in the calcifications of cardiac bioprostheses. Such calcifications are more frequent during growth, pregnancy and renal failure when bone gla-protein levels are elevated. We investigated whether bone gla-protein and other markers of calcium metabolism play a role in bioprostheses calcifications. Forty-seven patients were separated into 2 groups according to the presence (group A, n = 9) or absence (group B, n = 38) of bioprostheses calcifications, as assessed by echo-doppler and surgery. Plasma levels of calcium, phosphorus, magnesium, creatinine and alkaline phosphatases were measured by standard laboratory methods, parathormone and those of bone gla protein by specific radioimmunoassays. Results (mean +/- SEM) were compared (group A versus group B, P < 0.01) using Student's test and one-factor variance analysis (ANOVA). Age was similar in both group (53 +/- 12.9 vs 50 +/- 12.3 yrs), whereas duration of implant was greater in group A (104 +/- 12.4 vs 66 +/- 6.5 months, P < 0.01). No statistically significant difference was found between group A and B concerning biochemical and/or hormonal markers of calcium metabolism. These negative results merit to be discussed, and further studies will be needed to explore the potential role of circulating bone gla-protein in bioprostheses calcifications. PMID- 8511115 TI - [Biological markers of cancer. Critical study]. AB - The clinical use of tumor-associated markers still raises several problems, due to the lack of specificity of most biological markers and to insufficient evaluation of their true benefit for the patients. Only two markers, calcitonin and alpha-fetoprotein, markers of medullary thyroid carcinomas and of hepatocellular carcinomas respectively, have been proved useful in screening high risk populations for tumors. The usefulness of the prostate specific antigen in screening for prostatic cancer is still debated. Human chorionic gonadotropin and its free beta subunit are useful in the early detection of testicular cancer. Other biological makers, such as CA 15-3 for breast cancers, CA 19-9 for either gastric or pancreatic cancers, anc CA 125 for ovarian tumors are useful mostly in the follow-up of these tumors. Finally, measurements of tumor markers and analysis of their results must be performed by biologists or physicians who use tumor-associated markers routinely. PMID- 8511114 TI - [IgG kappa myeloma with Fanconi's syndrome and crystalline inclusions. Immunohistochemical and ultrastructural study]. AB - An IgG kappa light-chain myeloma, remarkable for the presence of inclusions in plasmocytes and proximal renal tubular cells, was discovered during investigations for renal failure associated with partial Fanconi's syndrome. An immunohistochemical study showed that the crystalline inclusions were positive for IgG and kappa light-chain in plasmocytes and exclusively for kappa light chain in the renal tubular cells. An ultrastructural study showed that the inclusions were localized in lysosomes and had a 55 A periodicity. This case is similar to the forty odd myelomas or light-chain diseases reported in the literature and revealed by Fanconi's syndrome. Their prognosis is good, with a slow progression towards late renal failure. In our patient the preference of lesions for proximal tubular cells, the site of protein catabolism, was particular since in myelomas they are usually located in the distal tubular cells. PMID- 8511116 TI - [Severe carpal tunnel syndrome during pregnancy]. PMID- 8511117 TI - [Antiprothrombinase antibodies in Horton's disease]. PMID- 8511119 TI - [Cervical spine: why do I manipulate?]. PMID- 8511118 TI - [Treatment of akinetic mutism with bromocriptine]. PMID- 8511120 TI - [Visceral leishmaniasis: a case in Tahiti at the end of dengue after a 2-year asymptomatic carriage]. PMID- 8511121 TI - [Disseminated cytosteatonecrosis of pancreatic origin]. PMID- 8511122 TI - [Tubular gastrostomy under celioscopy]. PMID- 8511123 TI - [Motor neuropathies with antiglycolipid antibodies]. PMID- 8511124 TI - [Intra-alveolar hemorrhage in Wegener's granulomatosis. Retrospective study of 9 cases]. AB - Among 66 patients with Wegener's granulomatosis, 9 had an intra-alveolar haemorrhage which revealed the disease. The diagnosis was based on dyspnoea (n = 9), haemoptysis (n = 9) and anaemia (n = 9) with a mean haemoglobin level of 8 +/ 1 g/dl. Radiology showed bilateral alveolar infiltrates (n = 9), and numerous siderophages were found either in the alveolar lavage fluid (n = 7/7) or in sputum (n = 2). In every case, the alveolar haemorrhage was accompanied by a rapidly progressive extracapillary glomerulonephritis and by lesions of the upper airways which preceded it by several months or years. All patients received corticosteroids combined, in 8 cases, with cyclophosphamide. The respiratory disease improved rapidly, in contrast with the renal disease which became worse (n = 5). Two patients died in the acute phase of the vasculitis: one of acute renal failure, the other of infectious shock. PMID- 8511125 TI - [Echocardiographic abnormalities in the stage IV of HIV infection]. AB - Fifty patients in stage IV of HIV infection (including 41 AIDS patients) were prospectively studied by echocardiography. Thirteen of them showed abnormalities: 4 had pericardial effusion, 1 endocarditis, 7 myocardial disorders and 1 primary pulmonary arterial hypertension. Pericardial effusion, also present in patients who had pleuropulmonary Kaposi's sarcoma, was not specific. Myocardial disorders concerned the diastolic function in 1 case, the segmental kinetics in 2 cases and the whole systolic function in 4 cases (3 had congestive myocardiopathy and 1 had transient systole alteration without left ventricular dilatation). The mechanism of global left ventricular disorders was multifactorial, and several hypotheses were discussed: infectious myocarditis, adrenergic or nutritional deficiency myocarditis, cardiotoxicity of antiviral drugs, common pathology with HIV encephalopathy. The prognosis of congestive myocardiopathy was poor in AIDS patients and undetermined in stage IV non-AIDS patients. Echocardiography is capable of detecting these lesions, and its use may contribute to a better care of these patients. PMID- 8511126 TI - [Migration of an Antheor filter in the pulmonary artery. A case]. AB - Migration of an Antheor caval filter into the pulmonary artery was observed in a 66-year old male patient referred for multifocal pulmonary embolism in a context of heparin-induced thrombocytopenia. The inferior vena cava was of small diameter (18 mm). The filter was removed under cardio-pulmonary bypass and total heparinization, despite the proven thrombocytopenia. The postoperative period was marked by tamponade which had to be drained. The long-term results were satisfactory. This seems to be the first documented case of Antheor caval filter migration into the cardiac cavities. PMID- 8511127 TI - [Ocular toxoplasmosis: demonstration of free Toxoplasma in the aqueous humor]. PMID- 8511129 TI - [Circulating lupus anticoagulant in typhoid fever]. PMID- 8511128 TI - [Role of interleukin 6 in the edema phase of patients with severe burns]. PMID- 8511130 TI - [Hypoglycemia caused by interference between an angiotensin-converting enzyme inhibitor and a hypoglycemic sulfonamide]. PMID- 8511131 TI - [Exogenous surfactants in infants. Indications and limitations]. PMID- 8511132 TI - [Bilateral aorto-iliac prosthesis. Long-term results]. AB - Over a 12-year period (1975-1987), 565 patients (male: 94.5 percent; female: 5.5 percent) underwent aorto-iliac bilateral reconstruction. The operations were performed by the same surgical team and all patients were followed up for 13 years. The patients' mean age was 59.4 years; 16.6 percent were over 70; 16 percent had a non-fissured aneurysm. The postoperative mortality rate was 2.8 percent, with relatively few deaths of cardiovascular origin (0.5 percent). The late mortality rate was significantly higher than that of an age-matched control population. Arteritis and its surgical treatment accounted for a low proportion of late deaths: 10.7 percent as opposed to other cardiovascular diseases (33 percent) and chiefly to cancer (39 percent)--a figure not found in other reports. Five percent of the patients had to be amputated soon after the operation or later; this is a low figure compared with the 33 percent of patients who had one limb threatened before reconstructive surgery. After the aorto-iliac reconstruction 81 percent of the patients remained considerably improved at 5 years and 67 percent at 10 years. Long-term arterial patency was satisfactory (95 percent at 5 years, 90 percent at 10 years). This type of surgery, therefore, benefits the patients' functions and their life: it avoids rupture of aneurysms and sedentarity due to a disabling intermittent claudication, and it considerably increases the duration of life. PMID- 8511133 TI - [Diabetic thoracoabdominal neuropathy. Clinical and electrophysiological study with evaluation of the autonomic nervous system]. AB - We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system. PMID- 8511134 TI - [Nociceptive flexion reflex of the leg. Use after surgical treatment of herniated disk]. AB - In patients suffering from acute sciatica due to herniated disk Lasegue's manoeuvre inhibits the leg flexion nociceptive reflex (RIII reflex) in either the ipsilateral or the contralateral limb. This is thought to be due what is called "diffuse noxious inhibitor control" modulating the activity of a group of convergent spinal neurons. The purpose of this study was to determine whether surgical resection of the herniated disk in patients suffering from sciatica might relieve this so-called "counter-irritation". Among 10 patients whose sciatica resulted from herniated disk, the decrease in amplitude of the RIII response observed when Lasegue's manoeuvre is applied disappeared in 7 patients, 6 to 8 days after surgical resection of the herniated disk. These results suggest that this test might be a useful tool for postoperative prediction of radicular compression. PMID- 8511135 TI - [Primary lipoprotein lipase deficiency. Study in Quebec]. AB - Primary lipoprotein lipase deficiency is a rare autosomal recessive disease that causes hyperchylomicronaemia complicated by pancreatitis. Recent advances in molecular biology have facilitated its diagnosis and enabled heterozygous subjects to be identified. Numerous mutations are responsible for lipoprotein lipase deficiency. In some eastern regions of Quebec province homozygotes have been found in very high concentrations: up to 200 times the frequency observed in all other parts of the world. Heterozygocity may represent 1 in 40 subjects. Two mutations account for 95 percent of the Quebec cases, and each of them has its own characteristic geographical distribution. These peculiarities have been ascribed to a founder effect suggested by the analysis of the first colons' migrations and by the study of homozygotes' genealogy. Most of the ancestors of the Quebec carriers came from northwestern France in the 17th century, and heterozygotes alleged to be healthy carriers of the trait may have a predisposition to premature development of a cardiovascular disease. Their blood lipid levels and the composition of their lipoproteins (particularly those with low density) are suggestive of an atherogenic potential similar to that of hyperapobetalipoproteinaemia or familial combined hyperlipidaemia. Molecular biology would be a useful tool to confirm or infirm this hypothesis and to identify subjects at risk of developing a cardiovascular disease. PMID- 8511136 TI - [Unusual mixed pituitary adenoma with gonadotropic, somatotropic hormones and prolactin]. PMID- 8511137 TI - [Efficacy of triamterene in hydrocephalus in adults]. PMID- 8511138 TI - [Duodenal ulcer: truncal vagotomy is back]. PMID- 8511139 TI - [Purulent Staphylococcus aureus myocarditis responsible for cardiogenic shock]. PMID- 8511140 TI - [Status and perspectives on xenografts]. PMID- 8511141 TI - [Neoplastic pericarditis. Study by thoracotomy and biopsy in 80 cases]. AB - Between 1969 and 1992, eighty cases of malignant pericarditis were studied by thoracotomy and biopsy, which made it possible not only to assert the diagnosis but also to dry the pericardial effusion by creating a pleuro-pericardial window. In 75 cases a cardiac tamponade of varying severity required surgical heart decompression. Pericarditis revealed the neoplasia in 53 cases and complicated a known cancer in 27 cases (23 carcinomas, 2 malignant melanomas included). In 63 cases (2 metastatic malignant melanomas, 7 sarcomas and 54 carcinomas) the disease was rapidly fatal. On the other hand, 17 patients with certain types of neoplasia revealed by pericarditis (12 with malignant lymphoma, 5 with non encapsulated thymoma) have survived under an appropriate treatment. In addition to curing the immediately life-threatening tamponade, thoracotomy with pericardial biopsy determines the nature of the lesion and, consequently, its specific treatment. PMID- 8511142 TI - [Antiphospholipid syndrome. A new cause of bilateral hemorrhage of the adrenal glands. 4 cases]. AB - Four cases of adrenal insufficiency due to bilateral adrenal haemorrhage in patients with antiphospholipid syndrome are reported. The 1st patient had repeated episodes of thrombosis on a background of altered general condition; he was examined by computed tomography (CT) which showed enlarged and presumably tumoral adrenal glands; adrenal insufficiency was present and improved under hormone replacement therapy; the thrombotic episodes were attributed to the antiphospholipid antibodies; after a 5-year follow-up the antiphospholipid syndrome remained alone, and further examinations showed progressive adrenal atrophy. The 2nd patient had systemic lupus erythematosus with thrombocytopenia; because of abdominal pain CT was performed, showing bilateral adrenal enlargement; treatment with intravenous pulses of cyclophosphamide and high-dose immunoglobulins combined with corticosteroids failed, and splenectomy was performed disclosing an old adrenal haematoma which was evacuated. The 3rd patient had bilateral and asymmetrical adrenal hypertrophy at CT; subsequently, systemic lupus erythematosus was diagnosed with anti-prothrombinase and anticardiolipin accounting for the initial findings; follow-up examinations showed the formation of pseudocysts in the adrenals; following myocardial infarction the patient died of cerebral haemorrhage, and autopsy confirmed the presence of old, bilateral adrenal haematomas. The 4th patient had recurrent vein thrombosis associated with distal ischaemia, which prompted CT in search of a neoplasia; this examination revealed 2 large adrenal haematomas while anticardiolipin antibodies were found. In patients with antiphospholipid syndrome any functional or morphological abnormality of the adrenals should prompt a search for bilateral adrenal haemorrhage. Conversely, in all cases of adrenal insufficiency a search for antiphospholipid antibodies should be part of all aetiological investigations, and this search should be carried out prior to withdrawing corticosteroids in cases of systemic lupus erythematosus with antiphospholipid antibodies. PMID- 8511143 TI - [Leiomyoma of the anal canal. A case]. AB - We report a case of leiomyoma of the anal canal, a very rare benign tumour, which was followed up for more than 7 years. With only one exception (10 years), the 14 cases previously published were watched during a short period. This tumour is characterized by the lack of absolute pathological criteria of benignity, even in the total of operative specimens examined, and by a tendency to recurrence, perhaps due to an insufficient local excision. This simple surgical operation seems to be justified, provided the patient remains under close supervision during 5 to 10 years. PMID- 8511144 TI - [Toxoplasmosis in pregnancy. Diagnosis and new therapeutic possibilities]. AB - Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained. PMID- 8511145 TI - [Biological markers of bone metabolism]. AB - During the last few years non-invasive methods to measure bone metabolism have been the object of intensive studies, chiefly because of the need for sensitive and specific markers to be used in the exploration of osteoporosis. Bone formation can be evaluated by assays of serum alkaline phosphatase, osteocalcin and collagen extension peptides. Bone resorption can be quantified by assays of urinary hydroxyproline and urinary pyridinoline excretion, and by assay of tartrate-resistant acid phosphatase in plasma. These markers have different sensitivity and specificity. At present, serum osteocalcin and urinary pyridinoline are the most effective markers, notably to evaluate bone metabolism in menopausal women and in patients with vertebral osteoporosis. In the near future a battery of tests based on a combination of the most effective markers will probably be used to study the complex abnormalities of bone metabolism which occur in bone diseases, and in particular in osteoporosis. PMID- 8511146 TI - [Benign acute pericarditis after vaccination against hepatitis B]. PMID- 8511147 TI - [Thrombocytopenia associated with positive HCV serology in adults]. PMID- 8511149 TI - [Association of Streptococcus bovis endocarditis and liver cirrhosis]. PMID- 8511148 TI - [Algodystrophy of the hip during pregnancy]. PMID- 8511150 TI - [Elevation of serum ferritin in Still's disease in adults]. PMID- 8511151 TI - [Rhabdomyolysis in hypothyroidism. Favourable role of amiodarone]. PMID- 8511152 TI - Whatever happened to the nursing shortage? PMID- 8511153 TI - Structured support at a time of crisis. Treatment of paracetamol overdose. AB - The increasing incidence of paracetamol overdose has been linked to its ready availability over the counter. Treatment is stressful and unpleasant for both nurse and patient, so it is essential a calm supportive approach is adopted throughout. PMID- 8511154 TI - Making sense of comparative values. Evaluation of trials of constant low pressure supports. AB - Various clinical trials have been undertaken to assess the benefits of constant low pressure supports. Their findings may have valuable bearings on decisions regarding the purchase of these products. PMID- 8511155 TI - What influences care planning? Nurses' attitudes towards care plans. AB - Positive use of care planning is integral to good patient care. A study was thus undertaken to assess the influence ward sisters and charge nurses have on ward teams' care planning and the effect of education on attitudes towards its use. PMID- 8511156 TI - A flexible path to permanent change. Implementing standard setting in an intensive therapy unit. AB - Nurses working in an intensive therapy unit decided to implement a standard designed to produce long-term benefits in patient care. A standard was devised which reflected the needs and views of all members of the nursing team, as this was perceived as the best way of ensuring genuine change. PMID- 8511157 TI - Motor neurone disease: a progressive disease requiring a coordinated approach. AB - 1. Such a variety of causes are implicated for MND that it is unlikely a single cause exists. 2. There is no actual treatment for the disease other than alleviating symptoms and improving function by the use of aids and appliances. 3. Care of people with MND is highly specialised, requiring multidisciplinary cooperation to ensure effective patient care. 4. Nurses owe it to their patients to acquaint themselves with the disease and support networks available. PMID- 8511158 TI - Let us extend our knowledge base. Assessment and management of fungating malignant wounds. AB - Little research has been undertaken on the management of fungating malignant wounds, and current practice relies more upon an exploratory approach than research-based evidence. This article presents a detailed problem-solving framework for the assessment and management of these wounds, and can be used in conjunction with the wallchart outlining the plan enclosed free with this issue. PMID- 8511159 TI - Care improves while costs reduce. The clinical nurse specialist in total parenteral nutrition. AB - Inserting feeding lines into patients requiring total parental nutrition (TPN) is expensive and time consuming. Expanding the role of the clinical nurse specialist in TPN enabled this procedure to be performed percutaneously on the ward, cutting costs, freeing doctors' time and improving patient care. PMID- 8511160 TI - Good communication heralds successful integration. Evaluating the roles of community specialist and general nurses. AB - Nurse specialist roles are becoming more prevalent in community care. Do nurse specialists working in the community enable services to provide better care for their patients? How can specialist and general nurses work together to provide optimum holistic care in the community? PMID- 8511161 TI - Can you tread this emotional high wire? Balancing elderly people's rights and independence against risks they pose. AB - When elderly people cannot fully care for themselves, difficult issues are raised regarding their rights and independence, as well as the risk they pose to themselves. How are such issues resolved in deciding how care is provided to these people? PMID- 8511162 TI - Time for a change in direction. Effects of poverty on ill health and service provision. AB - Recent studies point to a causative link between poverty and ill health, and show that people from low income groups often lose out in the provision of healthcare support. A campaign to ensure that service provision is targeted to those most in need may help address the source of this problem. PMID- 8511163 TI - Look beyond the patient. PMID- 8511164 TI - 21st Annual Meeting of the American Society for Photobiology. Chicago, Illinois, June 26-30, 1993. Abstracts. PMID- 8511165 TI - Motion-induced aversions during and after recovery from olfactory nerve section in mice. AB - Bilaterally nerve-sectioned male albino mice were given access to a novel food (almond) and then body rotated for 50 min. Two days later the mice were given a second access to almond. The procedures were repeated after recovery of olfactory function. Mice formed a presumably taste-mediated aversion while anosmic and a second flavor-mediated aversion (to the same food) after the return of olfactory function. Rotation control subjects formed only the standard flavor aversion subsequent to the first pairing of novel food and motion. It appears that olfaction is required for recognition of a food as novel. PMID- 8511166 TI - Stress-induced hypertension in the borderline hypertensive rat: stimulus duration. AB - Blood pressure and circulating catecholamines were evaluated in borderline hypertensive rats (BHR) that were exposed to daily sessions of either short (20 min) or long (120 min) duration air-jet stimulation. Indirect measures of systolic blood pressure indicated that within 2 weeks both experimental groups developed stress-induced hypertension in comparison to home cage controls. Animals exposed to 120 min stress sessions had significantly higher systolic blood pressure relative to the 20 min group. However, direct measures of blood pressure taken after 5 weeks of daily stress did not reveal any differences between the stress groups. Daily measurements indicated that acute changes in blood pressure during stress were modest and transient, suggesting little contribution to the chronic elevation in blood pressure observed as a consequence of stress. Circulating catecholamines were significantly increased by the stressor. Epinephrine returned to baseline within 60 min, although norepinephrine remained elevated throughout the 120 min session. The results indicate that increasing the duration of daily air jet stimulation did not impact the development of stress-induced hypertension over the 5-week measurement period. PMID- 8511167 TI - Comparison of the feeding responses to bacterial lipopolysaccharide and interleukin-1 beta. AB - To further investigate the idea that endogenous interleukin-1 plays a major role in the anorectic effect of bacterial lipopolysaccharide (LPS), feeding responses to recombinant human interleukin-1 beta (rhIL-1 beta) and LPS, as well as crosstolerance or -sensitization between both compounds, were investigated in rats. Intraperitoneally (IP) injected paracetamol (50 mg/kg body weight = b.wt.) markedly attenuated the anorectic effect of rhIL-1 beta (50,000 LAF units/kg b.wt., IP), but was clearly less effective in attenuating the anorectic effect of LPS (100 micrograms/kg b.wt., IP). As in previous experiments of ours, repeated IP injections of rhIL-1 beta (three injections of 50,000 LAF units/kg b.wt. on experimental days 1, 4, and 10) resulted in sensitization to the anorectic effect rhIL-1 beta, whereas repeated IP injections of LPS (three injections of 100 micrograms/kg b.wt. every second day) resulted in LPS-tolerance. Sensitization to the anorectic effect of rhIL-1 beta did not affect the anorectic response to LPS. Likewise, LPS-tolerance did not alter the anorectic response to rhIL-1 beta. RhIL 1 beta suppressed feeding by reducing meal frequency and meal size. In contrast, the anorectic effect of LPS was due entirely to a reduction of meal frequency. The results indicate that rhIL-1 beta and LPS do not affect feeding through exactly the same mechanism. PMID- 8511169 TI - Encoding of a nonmonotonic serial pattern: role of the dorsal hippocampus and amygdala. AB - The present experiment examined the effects of lesions of the hippocampus, amygdala, or combined hippocampal + amygdala lesions on the acquisition of a presumably difficult serial pattern. Lesioned rats, sham-surgical and nonsurgical control rats were trained in a runway to track one of a four-element series of Noyes food pellets consisting of 14-0-3-7 pellets, respectively. Control rats were capable of tracking the elements of the series. Tracking developed in the amygdala-lesion group by the middle stages of training, but tracking did not develop in the hippocampal-lesion group until the end of training and failed to develop in the hippocampus + amygdala-lesion group. The results are discussed in terms of hippocampus and amygdala involvement in working memory processes. The role of each structure in processing the temporal and affective attributes of the task is considered. Presumably, the hippocampus is necessary for tasks requiring the sequential coding of information. The hippocampus appears to maintain a temporal record of the elements of the series providing the rat with the ability to track which stimulus elements have been presented and which have not. In addition, by processing the affective attributes of the task, the amygdala appears to mediate mnemonic processes. PMID- 8511168 TI - Metabolic and functional changes in lymphocytes and macrophages as induced by ageing. AB - Key enzyme activities of glycolysis, pentosephosphate pathway, Krebs cycle, and glutaminolysis were measured in lymphocytes and macrophages of 3- and 15-month old rats from the control, thioglycollate-injected, and Walker 256 tumor implanted groups. The percentage of phagocytosis, phagocytic index, and production of H2O2 in macrophages and the rates of [2-14C]-thymidine and [5-3H] uridine incorporation in cultured lymphocytes were also determined. The results indicate that the percentage of phagocytosis was not affected but the phagocytic index increased by twofold as a consequence of ageing, whereas the production of H2O2 reduced. The rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation in lymphocytes from aged rats were lower as compared to those of mature animals in the three groups. Taken as a whole, the results of enzyme activities suggest that ageing may reduce the capacity for glucose utilization in lymphocytes and macrophages under the three conditions. Lymphocyte and macrophage glutamine metabolism was not markedly affected by ageing. Therefore, an impaired glucose metabolism during ageing may be one important mechanism for the alteration in lymphocyte proliferation and macrophage phagocytosis observed and also for the modification of the response to inflammatory and tumor challenges. PMID- 8511170 TI - The effect of bilateral sectioning of the chorda tympani and glossopharyngeal nerves on the sweet taste in the mouse. AB - The chorda tympani nerve (CT) and the glossopharyngeal nerve (GL) have been considered important nerves for the sense of taste. We studied the effect of bilateral sectioning of the CT and/or GL on the sweet taste in the mouse. Before and after surgery we analyzed the daily drinking patterns, using the two-bottle preference test method. The normal mouse drank the low concentration sucrose solution (0.0125 M) more than distilled water. This report showed that the mouse who was bilateral sectioned, both CT and GL or bilateral sectioned CT, rejected drinking the low concentration of sucrose solution. In contrast, the mouse who was bilateral sectioned GL drank the low concentration sucrose solution like the normal mouse did. These phenomena suggested that the fungiform papilae play an important role to detect the low concentration of sucrose (0.0125 M) as a sweet favorable taste substance. PMID- 8511171 TI - Taste intensity performance in patients irradiated to the head and neck. AB - Decrements in taste-detection thresholds during radiotherapy and subsequent recovery in the months after therapy are well documented. However, few studies have explored suprathreshold taste intensity perception in radiation patients. This cross-sectional study compared taste function in 15 men postradiation with a group of 23 healthy, nonirradiated male volunteers. A direct-scaling procedure was used to assess taste intensity perception of the four basic taste qualities. Patients performed nearly as well as control subjects on objective measures of suprathreshold functioning. Postradiation intensity judgments of salty (sodium chloride), sweet (sucrose), and bitter (quinine sulfate) solutions were not significantly reduced. Subtle, age-related taste impairments were identified for sour perception (citric acid) postradiotherapy. Younger patients judged citric acid to be more intense than did age-appropriate control subjects, whereas older patients judged it to be less intense. Moreover, younger patients were likely to be midly dysgeusic, whereas older patients appeared to be hypogeusic for citric acid. This study provides evidence for near normal suprathreshold taste intensity perception in patients who have received head and neck irradiation. PMID- 8511172 TI - Transiently evoked otoacoustic emission amplitudes change with changes of directed attention. AB - The effect of a visual and of an auditory task on the cochlea was studied by transiently evoked otoacoustic emissions (TEOAEs). TEOAE amplitude decreased during visual and auditory attention for all 13 subjects tested. The decreased TEOAE activity was noted predominantly within the 960 to 1920 Hz range during visual attention and within the 1920-2880 Hz range during auditory attention. Selective attention, by way of the olivocochlear medial efferent system, modifies cochlear micromechanical properties. Visual and auditory attention act on different areas of the cochlear partition. PMID- 8511173 TI - The effect of protein source on the diets selected by pigs given a choice between a low and high protein food. AB - To test the effect of the protein source on the diet selection of growing pigs, four foods of high protein concentration were made. Each food was based on a different protein meal: fish, soya bean, and two types of rape seed (with low and high glucosinolate contents), and was offered to growing pigs together with a food of low protein concentration (L), as a choice. Pigs given a choice between the fish or the soya bean meal-based food and L, selected a diet that met their protein requirements, as judged by their growth rates and food efficiency: the protein content of the selected diet declined systematically with pig weight. Pigs given a choice between the rape seed meal-based foods and L selected diets with a high proportion of L and, consequently, failed to meet their protein requirements. Given that the preference for L was more marked when the animals were given access to the rape seed meal higher in glucosinolates, it is suggested that their diet selection on these foodpairs was a tradeoff between minimising glucosinolate intake, which has potentially goitrogenic properties, and achieving a protein intake sufficient for maximum performance. This suggestion is supported by the fact that the fish meal-based food was preferred over the ones containing rape seed meal, and that the rape seed meal lower in glucosinolate content was preferred over the other when pigs were given a choice between them. PMID- 8511174 TI - Dietary amino acid complementation as a foraging strategy for wild birds. AB - Foraging birds finding foods containing protein of various quality could satisfy their amino acid needs by either 1) choosing only those foods that contain a suitable array of essential amino acids, or 2) choosing foods in amounts that permit complementation of constituent amino acids. We studied the abilities of sparrows (Zonotrichia leuchophrys gambelii) to use dietary amino acid complementation as a foraging strategy. We conducted two series of tests: 1) to determine if sparrows could select adequate portions from food pairs in order to compensate for reciprocal dietary deficiencies of either valine and lysine or lysine and threonine, and 2) to evaluate to what extent fortuitous (passive) complementation of dietary amino acids was constrained in sparrows by the magnitude of the dietary amino acid deficiency and the schedule of daily intakes of complementary foods. Small birds appear to have limited abilities to actively exploit dietary amino acid complementation. Birds offered a choice of two foods deficient in either lysine, valine, or threonine but of complementary compositions, reduced their daily intakes of food and body masses, but to a lesser extent (ca. one-half to one-third, and ca. one-quarter as much, respectively) than when either of the deficient foods were offered alone. Even passive complementation of dietary amino acids was severely constrained by both the magnitude of the dietary amino acid deficiency and the time course of feeding. The greater the amino acid deficiency, the less effective the complementation of dietary amino acids. The time course for effective and efficient complementation of dietary essential amino acids in these small, metabolically active animals was less than 2 h. PMID- 8511175 TI - Persistence of approach response after decerebration in newly hatched quail chicks. AB - The role of telencephalon in controlling the unconditional approach response was studied in newly hatched Japanese quail chicks by lesions. Approach to flickering light and a moving object were not diminished by ablation of various telencephalic areas, ranging from caudal forebrain lesions to complete bilateral hemispherectomy. Open field activity and tonic immobility were likewise unaffected. Results indicated that the neural mediation of unconditional sensory motor components of imprinting is anatomically separated from the telencephalon, where recognition memory is thought to be formed. PMID- 8511176 TI - Influence of combined estradiol and testosterone implants on the aggressiveness of nonaggressive female rats. AB - Female rats that had been cohabiting with a sterile male or with another female for 6 weeks were tested for aggression toward an unfamiliar female once each week for 3 weeks. Females that were not aggressive as a result of cohabitation with a sterile male were ovariectomized. Half were implanted with a Silastic tube containing estradiol (1 mm long hormone-filled space) and a tube containing testosterone (5 mm long hormone-filled space). The other half were implanted with empty tubes. All females that had been cohabiting with another female were ovariectomized and implanted with an estradiol- and a testosterone-filled tube. Three additional weekly tests of aggression were given beginning 1 week postoperatively. Females given hormone replacement displayed only a slight increase in aggression postoperatively. Females not given hormone replacement declined in aggressiveness. These results indicate that hormone replacement levels sufficient to maintain aggression in highly aggressive females following ovariectomy are not sufficient to produce a high level of aggression in females that have not become aggressive following cohabitation with a sterile male or that have been cohabiting with another female. PMID- 8511177 TI - Erectile mechanism in paraplegia. AB - Erection is generally viewed as a reflex mechanism that can receive higher CNS influences. Paraplegic men who have lost reflex activity from the genital area are, therefore, treated as irreversibly impotent. However, the innervation of the male reproductive system suggests that two neural pathways innervate the genitals. In theory, the second (thoracic-lumbar) pathway should compensate for the loss of the first (sacral) pathway in cases of low spinal lesions. Clinical practice, however, ignores the TL pathway as a basis for treatment of spinal cord injured men. This study used an animal model to demonstrate that the TL pathway could mediate penile responses in paraplegic rats. Eighty-five percent (85%) of spinal animals showed penile responses following hypothalamic (MPOA) stimulation despite a complete loss of peripheral erectile reflexes. These results not only have important implications from a clinical perspective, they further document the physiology of erection and support the view that erection is not a primary parasympathetic activity, but probably results from a sequence of sympathetic processes. PMID- 8511178 TI - Paw preference in mice: a reappraisal. AB - Paw preference in three strains (BALB/cA, C57BL/6J, Jcl:ICR) of mice was measured using the method of R. L. Collins (RPE score). We found that a) the patterns of paw preference were not so distinct as in previous studies, b) however, among these three strains, there were some differences in their patterns; namely, slight laterality was found in the C57BL/6J strain (RPE score distribution flattened), although no laterality was found in BALB/cA or Jcl:ICR strain (RPE score distributions bell shaped). These findings differ from those of previous studies. In this study we also propose a simplified method for determining paw preference in mice. PMID- 8511179 TI - The effect of dehydration level on the NaCl concentration chosen by rats. AB - The relationship between the level of dehydration (3%, 6%, and 8% body weight) and the preference for water and saline in the rehydration were assessed in rats for 15 h. At the 6% and 8% dehydration levels, rats provided with tap water and 0.9% NaCl solution simultaneously consumed more water than NaCl solution (calculated Na concentration was about 57 mEq/l) within 3 h and then consumed more NaCl solution than water (about 116 mEq/l). The shift of the Na concentration of fluid occurred when about 107% of lost cations and 82% of lost fluid were regained. Urine output and urinary Na output were about 14% of the ingested fluid during the initial 4 h; after that, the output was in amounts almost equal to the ingestion. However, the 3% dehydrated rats consumed almost equal amount of tap water and NaCl solution (about 68 mEq/l) throughout the 15 h. The result indicates that at more than 3% dehydration level, rats initially choose hypotonic NaCl solution, and the volume loss of body fluid is then regained by the consumption of almost isotonic Na solution. PMID- 8511180 TI - Cholecystokinin, but not bombesin, has interoceptive sensory consequences like 1 h food deprivation. AB - A comparison of the interoceptive sensory consequences of cholecystokinin, bombesin, and 1-h food deprivation was conducted in rats. In two experiments, rats were first trained to use stimuli arising from different degrees of food deprivation (1 and 24 h or 1 and 4 h) as discriminative signals for shock, and were then tested for generalized control of discriminative responding (i.e., conditioned freezing) by cues arising from injection of 4 micrograms/kg (Experiment 1 only) and 8 micrograms/kg cholecystokinin (Experiment 1A only), 12 micrograms/kg bombesin (BBS), and isotonic saline, respectively. The effects of these peptides on food intake were also assessed. In both experiments, BBS and cholecystokinin (CCK) each suppressed feeding relative to saline; however, generalization of discriminative responding was obtained only following CCK. Generalization depended on prior learning about food deprivation cues--CCK had little effect on freezing in rats that showed weak discrimination performance (i.e., rats trained with 1- and 4-h deprivation cues). The results indicated that CCK but not BBS produces interoceptive cues like those occurring under 1-h food deprivation. PMID- 8511181 TI - Sexual orientation and sexual motivation of the adult male rat. AB - Intact sexually experienced male rats were allowed to choose between staying in the vicinity of an estrous female or a sexually active male under different conditions of sexual arousal. In one group, the animals were allowed to perform two intromissions before the start of the partner preference test. In a second group, the subjects were allowed to reach a moderate level of sexual satiation by repeated ejaculations 24 h before testing. A third group was not given any pretreatment. Independently of the conditions of the pretreatment, all groups showed a clear female-oriented behavior. However, animals performing two intromissions before the test spent significantly more time with the female and showed a higher number of visits to her compared to the untreated controls. Males being sexually exhausted after repeated ejaculations showed a significantly lower level of female-oriented behavior than did the controls. It was concluded that the male's readiness to orient towards the female was affected by his motivational state. PMID- 8511182 TI - Food intake and estradiol effects on insulin binding in brain and liver. AB - Three groups of ovariectomized rats were treated for 6 days: 1) estradiol benzoate (100 micrograms/kg) (SC) and fed ad lib; 2) vehicle-injected controls fed the same amount of food as eaten by estradiol-treated rats; 3) vehicle injected, free-feeding controls. Specific binding of insulin to liver and hypothalamus slices was measured by quantitative film autoradiography. Estradiol treated rats lost weight (p < 0.001) and had elevated plasma insulin (p < 0.01). Liver insulin binding in rats with estradiol treatment was greater (p < 0.01) than in rats without estradiol, but was less (p < 0.05) than in controls fed the same food levels as consumed by the estradiol-treated rats. Therefore, with equal food intake, estradiol decreased liver insulin binding. Insulin binding in the dorsomedial, ventromedial, and arcuate nuclei of the hypothalamus was unchanged by food intake or estradiol, however. Thus, altered insulin binding in the arcuate, ventromedial, or dorsomedial nuclei of the hypothalamus is probably not involved in the effects of insulin or estradiol on food intake. PMID- 8511183 TI - Scopolamine affects response-to-change test involving 20-min retention interval after locomotor exploration in rats. AB - The tendency to select the T-maze arm that has been changed in brightness between two successive trials (response-to-change) was investigated. Our previous findings indicated that scopolamine injections (1.0 mg/kg) impaired responding to change of brightness in a choice trial (trial II) following a 1-min retention interval, when in the first acquisition trial rats could only inspect the white black T-maze arms through transparent partitions (the passive test). The drug was ineffective when rats were allowed locomotor exploration of the maze (the active test). The aim of the present experiment was to investigate the effect of the same dose of scopolamine on the active test involving a longer 20-min retention interval between the acquisition trial and the choice trial. The effect of cue salience also was examined by using grey-black arms. Rats injected with scopolamine (Scopo) 20 min before the acquisition trial performed in the white black maze on the chance level, whereas saline-injected rats (Sal) showed significant preference for the changed arm. Decreasing the cue salience impaired response-to-change in Sal rats (50% of changed arm choices) but had no further effect on performance of Scopo rats, presumably because of a floor effect. The postacquisition injection had a somewhat stronger effect than the injections preceding acquisition, which most probably reflects the state dependency phenomenon. The deficient performance due to scopolamine treatment that appeared in the present study at a longer retention interval could be interpreted in terms of increased forgetting. PMID- 8511184 TI - Characterization of pituitary mediation of stress-induced antinociception in rats. AB - Antinociception, induced by continuous cold-water swims (CCWS) and certain parameters of inescapable foot shock, is reduced in hypophysectomized rats receiving supplements of corticosterone and l-thyroxine. To assess which lobe of the pituitary gland is involved in this effect, the first experiment compared the effects of total hypophysectomy and posterior lobectomy in supplemented rats upon CCWS antinociception on the tail-flick and jump tests and upon continuous inescapable foot shock antinociception on the tail-flick test. Total hypophysectomy, but not posterior lobectomy, significantly reduced CCWS antinociception on both tests in supplemented rats relative to sham surgery. Both total and posterior hypophysectomy either reduced or potentiated foot shock antinociception as functions of shock intensity or duration of exposure in supplemented rats. To assess whether hormonal supplementation is necessary for the observed effects, the second experiment examined CCWS antinociception in sham operated and hypophysectomized rats that received either no hormonal supplements or corticosterone and/or l-thyroxine. These regimens failed to alter CCWS antinociception in sham-operated rats. Treatment of hypophysectomized rats with corticosterone and l-thyroxine either separately or together significantly reduced CCWS antinociception. In contrast, if hypophysectomized rats did not receive supplements, CCWS antinociception was significantly potentiated relative to sham-operated controls. These effects could not be attributed to treatment induced changes in either body weight or CCWS hypothermia. These data suggest that the anterior lobe of the pituitary gland and adrenal cortex are involved in the mediation and/or maintenance of CCWS antinociception. PMID- 8511185 TI - Genetic influences on daily intake and meal patterns of humans. AB - The heritability of nutrient intake was investigated with 109 identical and 86 fraternal adult twin pairs who were paid to maintain 7-day food intake diaries. Both classical analysis of heritability and linear structural modeling revealed significant additive genetic influences on body size, height and weight, and body fatness (body-mass index). Significant heritabilities were also found for the amount of food energy ingested daily, as well as its macronutrient, alcohol, and water content. Linear structural modeling analysis showed that 65% of the variance in energy intake was attributable to heredity. In addition, the pattern of intake, meal frequency, size, and meal macronutrient, alcohol, and water composition, were also found to have strong heritabilities. Linear structural modeling indicated that 44% of the variance in meal frequency and 65% of the variance in meal size was attributable to heredity. However, shared, familial environment had no significant impact on the levels or pattern of intake in adulthood. These results indicate that not only body size but also the pattern and amounts of nutrients ingested by humans in natural environments are strongly influenced by the immediate environment and heredity, but not at all by the familial environment. PMID- 8511186 TI - Medroxyprogesterone acetate decreases the sexual activity of male cynomolgus monkeys (Macaca fascicularis): an action on the brain? AB - Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant behavior of male sex offenders. In male cynomolgus monkeys, MPA reduces plasma testosterone (T) levels and sexual behavior, but the behavioral effects are clearly different from those of surgical castration. Because MPA is selectively taken up in unchanged form by the nuclei of neurons in the hypothalamus and preoptic area of male cynomolgus monkeys, and because it interferes with the uptake of T throughout the brain and pituitary gland, we have proposed that the behavioral effects of MPA may be mediated by brain mechanisms regulating sexual motivation that are relatively independent of circulating T levels. To test this hypothesis, eight castrated male cynomolgus monkeys bearing Silastic T implants SC were each observed during 60 min behavior tests with an ovariectomized, estrogen-treated female throughout three 4-week periods separated by 4-week periods without testing. After the first 4 weeks of testing, males received weekly IM injections of 40 mg MPA (six males) or vehicle (two males); the dose of MPA being equivalent on a body weight basis to those used clinically. Although plasma T was maintained in the upper range for intact males throughout the study, MPA treatment resulted in significantly decreased ejaculations and mounting attempts by weeks 5-6. These results demonstrated that the inhibitory effects of MPA on male behavior were independent of the reduction of plasma T levels, which points to a direct action on brain mechanisms controlling male sexual behavior. PMID- 8511187 TI - The peptide enterostatin may produce early satiety. AB - The time course of feeding, grooming, exploration, and sleeping behaviors has been measured following treatment with enterostatin, the signal pentapeptide from procolipase. The peptide was injected intraperitoneally prior to presenting food, and the frequency of feeding and grooming activity, drinking, and rest or sleeping were observed at 10-s intervals for 60 min. Enterostatin did not delay the onset of feeding but shortened the time spent eating compared to saline injected controls. Conversely, grooming activity appeared earlier following enterostatin, activity was reduced, and resting behavior occurred earlier with this peptide. There were no changes in the drinking behavior. For the first hour following enterostatin, eating represented 20.8% of the time, grooming 9.2%, activity 18.3%, and rest or sleep 47.2%, with drinking making up the other 4.4%. In contrast, saline-injected animals ate for 27.1% of the time, groomed for 12.4%, were active 28.5% of the time, had sleep or rest time equal to 27.9%, and drank for 4.1% of the time. In fasted animals, the onset of grooming, the decrease in activity, and the increase in time sleeping occurred earlier than with saline. These studies support the concept that enterostatin decreases food intake by producing early satiety. PMID- 8511188 TI - Odor matching and odor memory in the rat. AB - To assess olfactory matching-to-sample learning, rats were exposed to two odors separated by a 1-s presentation of clean air. If, and only if, the odors were identical, a response produced a water reinforcer. High levels of performance were maintained over a series of 10 novel three-odor matching-to-sample problems on this conditional go/no-go discrimination procedure. In general, performance accuracy improved over problems and errorless or near errorless performance on many stimulus combinations, particularly near the end of training, indicated acquisition of a learning set. There was little decrement in performance when the interstimulus interval was increased gradually from 1 to 10 s and matching-to sample was not disrupted when a novel odor was presented during the interstimulus interval. These results demonstrate that rats readily learn an olfactory matching to-sample task, maintain high levels of performance even with delays of 10-s between stimuli, and can acquire a matching-to-sample learning set. The outcomes are in agreement with prior studies demonstrating exceptional learning of instrumental tasks by rats when they are provided with odor cues. PMID- 8511189 TI - Development of some early sensorimotor behaviors in sodium-restricted rats. AB - Rats exposed to low levels of dietary sodium throughout development exhibit reduced chorda tympani nerve taste responses to sodium stimuli during adulthood, apparently due to altered activity of some hormone(s) or growth factor(s) during early development. We were concerned that such an alternation in the activity of some humoral factor(s) could affect development globally. To test this possibility, we utilized a battery of morphological and behavioral measures in neonatal, sodium-restricted rats, expecting serious deficits to be reflected in altered onset and expression of these behaviors. As compared with control rat pups, preweanling sodium-restricted rat pups exhibited greatly diminished body weight gain and delayed acquisition of several morphological features. However, in terms of sensorimotor development, no significant differences between sodium restricted and control rat pups were found. We interpret these results to indicate that despite significant somatic effects, sodium restriction may not influence the development of physical prowess or of early sensorimotor function in a global manner. PMID- 8511190 TI - Altered gustatory development in Na(+)-restricted rats is not explained by low Na+ levels in mothers' milk. AB - Placing pregnant rats on a sodium-deficient diet (0.03% NaCl) very early in gestation and then weaning the offspring (sodium-restricted rats) to the same diet precludes development of amiloride-sensitive sodium taste transduction pathways in the offspring. However, normal amiloride-sensitive sodium taste responses can be restored by permitting sodium ingestion by sodium-restricted rats. The present study tested the hypothesis that the concentration of sodium in sodium-restricted mothers' milk must be abnormally low in order to preserve altered gustatory function in the offspring. Other milk electrolyte and total protein concentrations were determined as well. Milk sodium was similar between sodium-restricted and control rat mothers at 10-13 and 16-20 days postpartum, as were levels of potassium and chloride. At 10-13 days postpartum, total protein was higher in milk from sodium-restricted mothers. Sodium-restricted mothers' milk calcium concentrations were higher versus controls at 16-20 days postpartum. These results indicate that the lack of gustatory amiloride sensitivity in sodium restricted rats cannot be attributed to deficient dietary sodium levels during the suckling period. PMID- 8511191 TI - Is prolactin related to activity and emotional reactivity in rats? AB - Recent studies have shown different relationships between hormones and personality in humans, including a relationship between prolactin levels and impulsivity. The aim of the present work was to study the relationships between basal levels of prolactin and some measures of activity and emotional reactivity in rats. One of the most consistent results showed a negative correlation between basal prolactin levels and activity. This finding is in line with the serotonergic theories of impulsive behavior and with the effects of dopamine upon activity. PMID- 8511192 TI - EGb 761 inhibits stress-induced polydipsia in rats. AB - The effect of daily treatments with Ginkgo biloba extract (EGb 761, IPSEN, France) on body weight and water intake of rats was followed for 15 days. During this period, two groups of rats, under slight ether anesthesia, were intubated and fed either EGb 761 (100 mg/kg b.wt. in 5% ethanol) or, for sham controls, 5% ethanol alone (6.6 ml/kg b.wt.). The increase in body weight was similar for the control and experimental groups. However, during the same period of time, the water intake, ml water/g b.wt./24 h, increased 37% in the controls. In EGb 761 treated rats, water intake remained unchanged. This suggests that EGb 761 treatment inhibits the development of polydipsia due to the stress of daily handling and intubation. PMID- 8511193 TI - A rapid test of rodents' vision using a modified open field apparatus. AB - Rats' responses to visual change in the environment were recorded in open field arenas in which a part or all of the visual environment could be altered without changing nonvisual features. Rats responded to a change in the appearance of one quadrant of a field by selectively reexploring the changed quadrant, and to a change in the whole environment by generally increasing their locomotor activity. The latter effect was equally large whether the change was from a patterned to a blank environment, or vice-versa. The present paradigms provide a rapid means of testing animals' vision. PMID- 8511194 TI - A new microcannula for injections in rat brains without disturbing social interactions. AB - A new cannula system is presented that allows intracerebral microinjections of neuroactive substances in freely moving rats in a social environment. By connecting a microcannula to a freely rotating stainless steel spring, small (0.2 microliter) injections can be made without disturbing the ongoing social interaction. This microinjection system can be used for instantaneous injections, but can also be used for microinfusions during a considerable longer period of time. PMID- 8511195 TI - Intermale aggression in mice: does hour of castration after birth influence adult behavior? AB - In the mouse, perinatally present testicular androgens promote the development of the propensity for adult intermale aggression. In the newborn male mouse plasma testosterone more than doubles during the first 2 h after birth and then falls rapidly to remain relatively low for the remainder of the 24-h period after birth. To study whether this surge in plasma testosterone influences aggressiveness we castrated some male mice within 1 h after birth i.e., before the surge. We castrated other males between 1.5-6 h after birth, or 1, 6, or 12 days after birth. Males were given testosterone as adults and tested for aggression for 5 weeks. Males castrated within 1 h after birth were not clearly different from males castrated 1.5-6 h after birth with respect to aggressive behavior, although males in both groups were substantially less aggressive than males castrated later in life. Thus, the perinatal surge in plasma testosterone in the mouse does not appear to make a unique contribution to the organization of mechanisms for intermale aggression. Rather, this surge is probably the initial stimulus that begins the postnatal process by which testicular hormones promote the development of the potential for adult aggressive behavior. This process appears to be complete by 6 days after birth. PMID- 8511196 TI - Reduced antinociceptive response to beta-endorphin in adult mice after chronic neonatal handling. AB - Male CD-1 mice were daily exposed to handling stress from second to the nineteenth days of life. Eleven and 16 days after the interruption of stress, handled (HA) and control nonhandled (UHA) animals were tested to measure the baseline threshold for the perception of thermal nociceptive stimulation by the tail-flick test (TFT) and to assess the presence of the Straub tail response (STR). On day 50 of life, the antinociceptive response induced by intracerebroventricular B-endorphin (BE) was also studied. The results indicated that animals chronically handled during the neonatal period, at the age of 5 weeks, showed a strong activation of the endogenous opioid system as demonstrated by the higher response latency to the TFT, as well as by the presence of a marked STR. Then, at the age of 50 days, there was no longer a difference in the TFT latencies between UHA and HA groups, but a significantly reduced response to the antinociceptive effect of BE was present in HA mice. PMID- 8511197 TI - Eating lowers defecation threshold in pigs through cholinergic pathways. AB - The effect of atropine on defecation threshold was compared to placebo pre- and postprandially in four 20- to 30-kg pigs. Stepwise balloon distention was performed 10 cm from the anal verge with a 5-cm latex balloon. Volume was increased in steps of 10 ml up to 200 ml of air or until the balloon was defecated (defecation threshold). Dependent measures were balloon volume, rectal pressure, rectal compliance, and an index of distention-induced contractile activity. Under placebo conditions, the volume and pressure to elicit defecation were significantly lower after feeding (p < 0.05). The distention-induced contractile activity significantly increased near the defecation threshold, but pre- and postprandial conditions were not different. No differences were seen between pre- and postprandial rectal compliance curves. Atropine abolished the postprandial decrease in defecation threshold, but did not affect rectal compliance. The increase in contractile activity at defecation threshold seen with placebo was abolished by atropine. These results show that eating lowers the defecation threshold in terms of distention volume and rectal pressure, and demonstrate that these changes are mediated through cholinergic pathways. PMID- 8511198 TI - Suppression of the lordosis reflex of female rats by efferents of the medial preoptic area. AB - In freely moving, estrogen- and progesterone-treated ovariectomized female rats, electrical stimulation of the medial preoptic area, which had been isolated dorsally from the septum by a horizontal knife cut (roof cut), caused immediate interruption of the lordosis reflex, a principal component of female reproductive behavior in this species. Neither the knife cut nor the stimulation affected their proceptive interactions with the males. Lordosis was interrupted in a graded manner in response to increased stimulus intensity, with a threshold at 30 microA. The optimal frequency was at 50-100 Hz. Lordosis was reinstated promptly by the termination of current application. The rapid time course distinguished the stimulation effect in the rats with the roof cut from that in the intact control animals, which was slow in its onset and recovery. In the sham-operated animals, an adjunct bilateral cut of the stria terminalis was sufficient to restore the rapid response as in the roof-cut animals. The roof-cut animals were sensitive to lower doses of estrogen than those without the knife cut; therefore, the preoptic area appears to be a separate entity from the septum in the inhibitory control of lordosis. The elimination of facilitatory neural components for this reflex, which enter the preoptic area dorsally via the stria terminalis, might be responsible for the prompt and exaggerated stimulation effect in the roof-cut animals. PMID- 8511199 TI - Aldosterone diurnal rhythm in the rat: a question of cross-reactivity? AB - Radioimmunoassay (RIA) of plasma aldosterone (ALDO) can be hampered by cross reactivity with plasma corticosterone (CORT). The purpose of this study was to determine and adjust for CORT crossreactivity when assaying for ALDO in blood samples taken throughout a 24-h period. Plasma was obtained from 10 adrenalectomized male Sprague-Dawley rats. Corticosterone-free plasma was spiked with 0, 50, 75, 100, 150, 200, and 300 ng/ml CORT. Aldosterone determination was performed by RIA. An equation for ALDO concentration adjusted for plasma CORT concentration was calculated (ALDO = measurable ALDO - 0.377 x CORT - 5.324). Twenty male Sprague-Dawley rats were adapted to a 12/12 light/dark cycle (lights on at 0900 h). They were divided into two groups based on body weight. Blood samples were obtained every 4 h beginning at 0900 h from rats in group 1 and beginning at 1100 h from rats in group 2. Distinct diurnal CORT and ALDO rhythms were observed. Corticosterone levels were highest at 2100 h (131.8 +/- 17.8 ng/ml) and lowest at 1300 h (04.6 +/- 1.8 ng/ml). Aldosterone levels were highest at 1900 h (276.50 +/- 53.60 pg/ml) and lowest at 1500 h (27.53 +/- 6.84 pg/ml). Corticosterone and ALDO levels were often significantly correlated (r > 0.60), but not at times when CORT and ALDO levels were at their highest. These results suggest that ALDO and CORT may be regulated by different mechanisms or may have a regulatory influence upon each other throughout the day/night cycle. PMID- 8511200 TI - Behaviors of rats with insidious, multifocal brain damage induced by seizures following single peripheral injections of lithium and pilocarpine. AB - Several domains of behavior were measured in rats (n = 465) 10 days to 100 days after induction of limbic seizures by a single subcutaneous injection of lithium and pilocarpine. These rats displayed enhanced intragroup aggression but normal muricide; gustatory neophobia and conditioned taste aversion were virtually eliminated. Severe working and reference memory deficits were evident within the radial arm maze. Both state-dependent memory and possible situation-dependent precipitation of spontaneous seizures were suggested. The behavioral changes were considered commensurate with the multifocal pattern of thalamic, hippocampal/amygdaloid, and limbic cortical damage. PMID- 8511202 TI - Forced extinction as a means to evaluate consolidation gradient of a passive avoidance response in the rat. AB - Passive avoidance response (PAR) consolidation gradient, and US (footshock) intensity/engram strength relationship were investigated by means of specific forced extinction procedure (30 min detention in the shock box without receiving punishment) in Wistar rats trained in the light-dark box apparatus. Different groups of rats (punished either with 0.8 or 1.2 mA footshock intensity) underwent detention at different postacquisition time delays: immediately or 1, 2, 4 days after acquisition training. By means of this purely behavioral paradigm, designed to investigate a specific PAR memory trace, previous results obtained by using diverse and sometimes unspecific memory-disrupting agents were fully confirmed: PAR strength and consolidation gradient are positively related to US intensity. The influence of differential generalization effects on extinction is discussed. An unexpected finding was that from engrams that are experimentally shown to be of unequal resistance to disruption, equal conditioned responses are obtained. PMID- 8511201 TI - Medialbasal hypothalamic deafferentation modulates feeding response to insulin in rats. AB - Medialbasal hypothalamic (MBH) deafferentation induces hypothalamic obesity accompanied by hyperphagia and hyperinsulinemia. Insulin is essential in developing and maintaining obesity, but the role of insulin in food intake in hypothalamic obesity is still unclear. The present study demonstrated that exogenous insulin increased food intake dose relatedly in MBH deafferented diabetic rats without developing hypoglycemia. Insulin administrations suppressed hyperphagia in the sham-operated diabetic rats. In contrast, in the MBH deafferented diabetic rats, insulin increased food intake in sow-related manner concomitant with a greater increased body weight gain than the sham-operated diabetic rats. The blood glucose levels of the MBH deafferented diabetic rats were at all time higher than those of the sham-operated diabetic rats and were hyperglycemic throughout the insulin treatment. These data indicate that insulin action on food intake mediated through the central nervous system is modulated by MBH deafferentation. This modulated insulin action may contribute to the pathogenesis on obesity in MBH deafferented animals. PMID- 8511203 TI - Dexfenfluramine treatment influences plasma catecholamines and energy substrate metabolism in rats. AB - The effect of chronic intragastric administration of dexfenfluramine (FFL, 1 mg/kg, twice a day), a drug that increases serotonergic transmission, on peripheral energy substrate metabolism was investigated. Rats were provided with permanent cannulas, allowing stress-free intragastric treatment and blood sampling. Fenfluramine-treated and control animals were submitted to strenuous swimming at days -2, 1, 4, and 7 relative to the onset of FFL treatment at day 0. Blood samples were taken before, during, and after exercise. Thereafter, possible changes in catecholamine sensitivity were investigated during intravenous infusions of norepinephrine (NE) and epinephrine. Finally, energy expenditure, including resting respiratory quotient (RQ), and carbohydrate and fat utilization were measured under baseline conditions. It was found that chronic administration of FFL led to a transient reduction in the exercise-induced increase of blood glucose concentrations. Plasma norepinephrine responses to exercise gradually increased in the FFL-treated animals. Baseline RQ was markedly increased in the FFL-treated animals, indicating an increase of carbohydrate utilization and a decrease of fat combustion. Total energy expenditure remained unchanged. The increased RQ was accompanied by increased sensitivity for NE and significantly decreased baseline concentrations of plasma free fatty acids. PMID- 8511204 TI - Metabolic and hormonal responses to hypothalamic administration of norfenfluramine in rats. AB - The effects of intrahypothalamic administration of norfenfluramine (NFFL), an anorectic agent that increases serotonergic transmission, on plasma concentrations of glucose, free fatty acids (FFA), and their regulating hormones were investigated in resting and exercising rats. Infusion of 5 micrograms NFFL in 0.125 microliter aCSF/min into the nucleus paraventricularis of the hypothalamus (PVN) caused a significant increase of blood glucose, plasma epinephrine (E), and corticosterone concentrations. Plasma levels of FFA, insulin, or norepinephrine (NE) remained unchanged. Lower doses of NFFL (0.5 and 0.05 microgram/min) did not affect peripheral metabolism. The effects of NFFL in the PVN were completely prevented by prior administration of a 5-HT1 antagonist, (S)-(-)propranolol. The exercise-induced increase of plasma NE was reduced after prior administration of 5 micrograms NFFL/min into the PVN. Plasma E responses tended to be increased. The exercise-induced alterations in glucose, FFA, corticosterone, and insulin were not affected by NFFL infusion into the PVN. The data suggest that activation of serotonergic mechanisms in the PVN might change the neurohormonal response to a stressor favouring the release of adrenal hormones above activation of the neuronal branch of the sympathetic nervous system. PMID- 8511205 TI - Timing and dose of amino acids injected into prepyriform cortex influence food intake. AB - The effects of time before feeding and dose of dietary-limiting amino acids (DLAA) injected into the prepyriform cortex (PPC) on intake of amino acid imbalanced diets were evaluated. Intake of imbalanced diet was increased from approximately 50% to approximately 75% of baseline when an optimal amount of DLAA (1 nmol L-isoleucine or 2 nmol L-threonine) was injected immediately prior to feeding. Injections made several hours prior to feeding were more effective, increasing intake of imbalanced diets to approximately 85% of baseline. Delivering two half-optimal doses of DLAA, several hours apart, increased intake of imbalanced diet only to the same level as a single injection of the optimal dose immediately prior to feeding. The increase in intake of a threonine imbalanced diet after injecting 2 nmol threonine 6 h prior to feeding was abolished if an additional 2 nmol threonine was injected immediately prior to feeding. It appears that it is the sum of the changes in tissue DLAA concentrations in the PPC that are recognized and influence food intake when amino acid imbalanced diets are fed. PMID- 8511206 TI - Strain-dependent escape deficit in two rat models of learned helplessness. AB - The shuttle box escape deficit produced by prior inescapable shock (IS) or by escapable shock (ES) was investigated in Koltushi high- (KHA) and low-avoidance (KLA) rat strains, genetically selected on the basis of divergent acquisition of a conditioned avoidance response in a two-way shuttle box. IS enhanced escape failures only in KHA rats. In contrast, ES produce escape deficit only in KLA rats. These data suggest that the learned helplessness interpretation of escape deficit might be relevant only when IS is administered to KHA rats. In the case of KLA rats exposed to ES, escape deficit represents a coping behavior. PMID- 8511207 TI - The pineal and circadian rhythms of temperature selection and locomotion in lizards. AB - The existence of a circadian rhythm of behavioral temperature selection has been demonstrated in lizards (Podarcis sicula) held on a thermal gradient in constant darkness. This rhythm becomes temporarily abolished during 1 week following parietalectomy and 2-3 weeks following pinealectomy. Parietalectomy does not affect the locomotor rhythm, while pinealectomy invariably lengthens the freerunning period of this rhythm. These results support the contention of separate control systems for the temperature selection rhythm and the locomotor rhythm. As neither rhythm is definitively abolished by parietalectomy and pinealectomy, other pacemaking components exist elsewhere in the circadian system of Podarcis sicula which can control both rhythms. PMID- 8511208 TI - Stress suppresses testicular and body weight in young Syrian hamsters under short photoperiod. AB - Two experiments were performed to investigate the effect of stress on testicular weight and body mass in young adult male Syrian hamsters under long or short photoperiods. We hypothesized that water or food deprivation causes stress and that the amount of stress depends on unpredictable timing of deprivation. More specifically, water or food deprivation on unpredictable days was considered more stressful for animals than regular deprivation on fixed days even if the total lengths of deprivation were the same for the two treatments. Experiment 1 showed that water deprivation on unpredictable days caused more suppressive effects on testicular weight and body mass than that on fixed days under short photoperiod. Experiment 2 indicated that unpredictable food deprivation on a quarter or half of the days throughout the 12-week testing period under short photoperiod also induced more detrimental effects on testes and body growth than predictable deprivation once every 4 days or every other day. These findings clearly suggested that the stress associated with water or food caused more suppressive effects on testicular weight and body mass than the shortage of water or food per se. PMID- 8511209 TI - Bright light affects alertness and performance rhythms during a 24-h constant routine. AB - The aim of the present study was to assess the stimulating effects of bright light (BL) on subjective and objective alertness. Eight subjects were exposed to either bright light or dim light (DL) during a 24-h constant routine (0900-0900). Bright light failed to modify either the 24-h course or the level of body temperature. Compared to DL, BL delayed the circadian trough of motor activity by 2 h. During the night, relative to the dim-light condition, BL significantly increased subjective and objective (EEG test) alertness and improved performances. Thus, BL exposure partly counteracted the effects of sleep deprivation and/or the circadian trough on alertness and performances. During the day, BL only improved the mood and motivation levels. However, the time course of mood and motivation was not affected by the BL exposure, a nocturnal circadian trough occurring at 0630 in both light conditions. PMID- 8511210 TI - Effects of single and repeated restraint on the social behavior of male rats. AB - The effects of a mild, nonpainful stressor (restraint, RT) on the social behavior of male rats were explored. Twenty-four hours after single or repeated RT, experimental subjects were confronted in a neutral cage with unfamiliar and naive opponents of the same sex and strain, matched for age and body weight. Introductory, affiliative, defensive, and offensive behaviors of the experimental animals were recorded for 20 min. Single RT caused a selective and dramatic inhibition of aggressive behavior, with no effects on defense. Allo-grooming, considered to be an appeasing and affiliative behavior, increased. Repeated RT caused basically the same effects, with an additional increase in retreat, a low intensity defensive behavior, and attend, possibly aimed at monitoring the unfamiliar partner. Habituation to repeated stress, therefore, did not occur, and the behavioral consequences of repeated RT were even greater than those of single stress. Additional tests of sexual behavior failed to reveal any deficit in sexual performance after single or repeated RT. PMID- 8511211 TI - Menstrual synchrony between mothers and daughters and between roommates. AB - Menstrual synchrony was examined in three groups of women: 1) mothers and their daughters; 2) women sharing a room in a private residence; and 3) women sharing a room in a dormitory. The intracouple difference in menstrual onset dates was the dependent measure. Mothers and daughters living in the same domicile displayed a significant degree of synchrony. Roommates in private residences were also synchronous, although not significantly more than roommates residing in dormitories. PMID- 8511212 TI - Crossfostering and early development of natural killer cytotoxic activity in various inbred mouse strains. AB - In the present study using crossfostering among three inbred mouse strains (C57BL/6, DBA/2, and Balb/c) we compared the effects of lactation with milk of different compositions on the development of NK cells cytotoxic activity. The results show that the pups from C57BL/6 and DBA/2 mice exhibit a significant early increase of NK cells cytotoxic activity when fostered by Balb/c dams, in comparison to those fostered by natural mothers. The analysis of proteins, lactose, and lipids showed difference among the strains for all components. Strain effects for days of lactation were also observed. The naso-anal length and the body weight of young mice showed differences with the strain of fostering mothers. The results indicate that the characteristic of maternal milk composition interacts with the inbred genetic susceptibility of the pups to elicit the full expression of the level of NK activity. PMID- 8511213 TI - Nuzzling in the gray short-tailed opossum. I: Delivery of odors to vomeronasal organ. AB - Nuzzling in the gray short-tailed opossum (Monodelphis domestica) is exhibited in response to conspecific odor deposits and is involved in chemosensory recognition. Nuzzling consists of bouts of repeated forward rubbing motions (with intermittent tapping) with the ventral aspect of the snout over the odor source, while moistening it with naso-oral secretions. The role of nuzzling in odorant d delivery to the vomeronasal organ (VNO) was investigated. Five opossums were allowed to nuzzle conspecific odor deposits mixed with 3H-proline. Histological sections of the snouts processed for autoradiography revealed very strong labeling of the VNOs, primarily the nonsensory epithelium. No labeling was observed in the olfactory epithelium. Unilateral closure of the oral opening to the nasopalatine canal resulted in labeling of the contralateral VNO only, implicating oral access to the VNO. Several distinctive structures appear to be associated with chemical access. An experiment in which 16 males and 16 females were given a preference test of dried nuzzling secretion versus dried distilled water established that the naso-oral secretions deposited during nuzzling do not have properties of scent marks. PMID- 8511214 TI - Nuzzling in the gray short-tailed opossum. II: Familiarity and individual recognition. AB - Nuzzling is a chemosensory exploratory behavior that enables South American gray short-tailed opossums to dissolved dry conspecific odor deposits in naso-oral secretions and incorporate them into their vomeronasal organs. This report documents that male opossums nuzzle novel (unfamiliar conspecific) male odors significantly longer than familiar (own of familiar conspecific) male odors or clean substrates. Such findings suggest that an important ethological function of nuzzling behavior involves individual recognition of conspecifics. The first experiment demonstrates that a very short (3-min) exposure to a conspecific odor is sufficient to establish familiarity. The second experiment reveals that a brief exposure results in prolonged (at least 2 h) odor retention. Both experiments establish that nuzzling by males is normally followed by scent marking; thus, novel male odors also elicit increased scent marking. We have identified four novel forms of scent marking by male Monodelphis domestica (ventral, chin, anal/cloacal, and neck) and our data suggest that marking style may be at least partially dependent on the physical properties of the substrata. PMID- 8511215 TI - Corticosterone modulation of dietary selection patterns. AB - Effects of corticosterone (CORT) supplementation on ad lib macronutrient selection and selection following food deprivation were examined in male adrenalectomized (ADX) Sprague-Dawley rats. The ADX rats self-administered CORT from drinking solutions of 0 microgram/ml, 20 micrograms/ml, or 40 micrograms/ml. Adrenalectomy attenuated weight gain, which CORT failed to completely restore. After 6 days, rats were deprived for 0 or 24 h. Adrenalectomy attenuated weight loss during deprivation; CORT failed to restore weight loss. Adrenalectomy reduced ad lib protein intake, which CORT failed to restore. Carbohydrate and fat intakes were not affected by ADX; CORT (40 micrograms/ml) increased fat intake. During the first hour of refeeding, ADX attenuated protein intake; CORT failed to restore intake. Corticosterone-supplemented rats consumed more fat than unsupplemented ADX rats. Over 24 h, unsupplemented, deprived ADX rats consumed less fat and calories than all other deprived groups. These results suggest that CORT affects weight gain in lean rats and modulates macronutrient selection both ad lib and following food deprivation. PMID- 8511216 TI - Long-term impairment of autonomic circadian rhythms after brief intermittent social stress. AB - This experiment was designed to examine the short- and long-term behavioral, cardiovascular, and thermoregulatory responses to brief intermittent agonistic confrontation in rats. The experimental procedure involves resident-intruder confrontations consisting of a 10-min period during which both animals are separated in the home cage of the resident, followed by a brief physical encounter leading to defeat of the intruder and a 10-min period, when the intruder was alone in the home cage of the resident. These 30-min-long confrontations were repeated on 5 consecutive days. Before the first confrontation with a resident, an intruder rat's telemetered heart rate and core temperature show a stable circadian rhythm that is entrained by the light cycle. Acutely, the confrontations produce immediate and large tachycardia and hyperthermia in intruders. A decrease in amplitude of the circadian rhythms for heart rate and core temperature, as detected by cosinor analysis, persists for at least 10 days after the last of five daily brief confrontations with the resident. The defensive upright posture is nearly absent during the first exploration of the resident's home cage, but is displayed by the intruder for one third of the available time before and after the fifth defeat. Intermittent brief social stress is sufficient to induce profound changes in defensive behavior and long-lasting depression of circadian rhythmicity that persist for weeks. PMID- 8511217 TI - Sympathoadrenal responses to glucoprivation and lipoprivation in rats. AB - The effects of glucoprivation and lipoprivation on sympathoadrenal outflow were investigated in rats with permanent intra-atrial catheters. Glucoprivation was induced by infusion of a hypoglycemic dose of insulin (3 U/kg) or by infusion of the glucose antimetabolite, 2-deoxy-D-glucose (2-DG, 200 mg/kg). Lipoprivation was induced by infusion of sodium mercaptoacetate (MA, 600 mumol/kg), which blocks beta oxidation of fatty acids. Stress-free blood samples for measurement of blood glucose, plasma nonesterified fatty acids (NEFA), and epinephrine (E) and norepinephrine (NE) concentrations were collected remotely before and after drug injection. Glucoprivation and lipoprivation differed significantly in their effects on the sympathoadrenal system. Both 2-DG- and insulin-induced glucoprivation appeared to increase adrenomedullary secretion selectively, leading to dramatically increased plasma E levels. Although plasma NE levels also rose during glucoprivation, other evidence suggests that this effect may be secondary to the rise in E. In contrast, MA-induced lipoprivation increased the outflow of NE from the sympathetic nerve endings without a significant effect on plasma E concentrations. Plasma E levels rose only late in the test, as blood glucose levels began to fall. Results indicate that glucoprivation and lipoprivation are distinct metabolic signals, each capable of selectively activating one branch of the sympathoadrenomedullary system and thereby facilitating the mobilization of metabolic fuels appropriate for the specific metabolic challenge. PMID- 8511218 TI - [A study of red cell sodium-lithium countertransport in affective disorders]. PMID- 8511219 TI - [The pension system for mentally disabled persons--a questionnaire study on the application form to the disability pension and the pension-less]. PMID- 8511220 TI - A functional cerebral response to frightening visual stimulation. AB - The defense reaction, a fundamental reflex in the human behavioral response to threat, is characterized by anxiety and increased activity of the sympathetic nervous system. To study changes in regional cerebral blood flow (rCBF) related to the defense reaction, volunteers with snake phobia were investigated with positron emission tomography. The relative rCBF during phobogenic visual stimulation was increased in the secondary visual cortex but reduced in the hippocampus, orbitofrontal, prefrontal, temporopolar, and posterior cingulate cortex compared with that observed during neutral visual stimulation. The relative rCBF under aversive stimulation was intermediate between phobic and neutral stimulation. The rCBF patterns observed are suggested to represent a functional cerebral correlate to the visually elicited defense reaction and its associated emotions. PMID- 8511221 TI - Quantitative electroencephalographic subtyping of obsessive-compulsive disorder. AB - Current neuropsychological, electrophysiological, and other imaging data strongly suggest the existence of a neurobiological basis for obsessive-compulsive disorder (OCD), which was long considered to be exclusively of psychogenic origin. The positive response of some OCD patients to neurosurgery, as well as the efficacy of agents that selectively block serotonin reuptake, lends further support to a biological involvement. However, a survey of the treatment literature reveals that only 45-62% of OCD patients improve with these specific medications. In a pilot study using a quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, we previously reported the existence of two subtypes of OCD patients within a clinically homogeneous group of patients who met DSM-III-R criteria for OCD. Following pharmacological treatment, a clear relationship was found between treatment response and neurometric cluster membership. In this study, we have expanded the OCD population, adding patients from a second site, and have replicated the existence of two clusters of patients in an enlarged, statistically more robust population. Cluster 1 was characterized by excess relative power in theta, especially in the frontal and frontotemporal regions; cluster 2 was characterized by increased relative power in alpha. Further, 80.0% of the members of cluster 1 were found to be nonresponders to drug treatment, while 82.4% of the members of cluster 2 were found to be treatment responders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511222 TI - Preliminary associations between motor procedural learning, basal ganglia T2 relaxation times, and tardive dyskinesia in schizophrenia. AB - The hypothesis that the caudate nucleus is involved in the pathophysiology of tardive dyskinesia (TD) in schizophrenia was investigated by examining motor procedural learning on the pursuit rotor task and basal ganglia T2 relaxation times (T2) determined using magnetic resonance imaging (MRI). Increased severity of TD was associated with shortened caudate T2 and decreased motor learning. Motor-learning scores of schizophrenic patients with and without TD did not differ significantly from those of normal control subjects, but motor learning in the schizophrenic patients correlated with caudate T2. The results suggest that a corticocaudate system subserves motor procedural learning and provide converging evidence from neuropsychological and MRI measures suggesting caudate involvement in TD. PMID- 8511224 TI - MRI-guided region of interest placement on emission computed tomograms. AB - The reliability of the placement of regions of interest (ROIs) on emission computed tomograms (ECT) with a semi-automated magnetic resonance image (MRI) guided method was compared with the reliability of manual ROI placement. MRI defined regions were transferred to the registered, co-planar ECT image after accounting for inter-image differences in rotation, translation, and scaling. Six single photon emission computed tomographic (SPECT) scans of normal control subjects were rated for caudate perfusion using the radiotracer N-isopropyl[I 123]-iodoamphetamine (IMP). The MRI-guided method had higher interrater reliability, lower variance of region location, and lower variance of region activity than the manual method. The manual method recorded higher mean regional activity than the MRI-guided method, possibly due to sample bias inherent in the manual method. PMID- 8511223 TI - Memory functions and temporal-limbic morphology in schizophrenia. AB - Several psychopathological and morphological studies support the hypothesis of temporal-limbic involvement in the pathophysiology of schizophrenia. In the present study, magnetic resonance imaging was used to evaluate the areas of the temporal lobes and related structures in 18 schizophrenic patients and 18 normal control subjects who were homogeneous for sex and age. The Wechsler Memory Scale was used to assess the memory functions of all subjects. Although the MRI data did not reveal any significant differences between the two groups, the Wechsler Memory Scale indices of memory functions showed significant differences between the schizophrenic patients and the control subjects. PMID- 8511225 TI - MMPI correlates of psychotherapy compliance among obsessive-compulsives. AB - The purpose of this investigation was to examine the relationship between compliance with a behavior therapy program and personality characteristics of obsessive-compulsive disorder (OCD) outpatients (n = 169), as measured by the Minnesota Multiphasic Personality Inventory (MMPI). Compliance was defined as the number of scheduled behavior therapy sessions canceled or missed by patients. Standard multiple regression analysis revealed that higher scores on scales 8 (Schizophrenia), 2 (Depression), and 0 (Social Introversion) contributed significantly to the prediction of compliance among OCD patients engaged in behavior therapy. PMID- 8511226 TI - On perception of complex sound in schizophrenia and mania. AB - Eleven schizophrenic psychotic and 11 manic psychotic patients have been compared with each other and with a reference group of 34 dentists with respect to their emotional experience of seven complex nonverbal sounds. A rating form was used which measures three factors of emotional perception: tension-relaxation (factor I), gaiety-gloom (factor II), and attraction-repulsion (factor III). Analyses of variance of the factor scores revealed main tendencies between the psychopathological groups in factor I and III, i.e. schizophrenic psychotics rated the sounds generally as more tense and more attractive than manic psychotics. The manic psychotics rated the sounds as generally less tense and very much more attractive than the other groups. In factor II the manic psychotics rated one piece as significantly more gay than the other groups. It is discussed in what ways these differences of complex sound perception may be related to characteristic symptoms of the psychopathological states. No convincing evidence may be drawn from this study supporting the assumption that the two psychopathological groups might differ in a specific way in relation to any elementary structural property of the sounds. PMID- 8511227 TI - Anxiety associated with kidney transplantation. AB - Anxiety associated with kidney transplantation was examined in a sample of 16 recipients. The incidence of anxiety amounted to 68.8% (11/16 cases) and 81.3% (13/16 cases) within the pre- and postoperation periods, respectively. One case indicated severe anxiety and finally developed dysthymic disorder after transplantation. Another case showed alexithymic features, which were associated with poor self-control, and strong defense mechanisms such as denial before transplantation. Although it is important for liaison psychiatrists to cure psychiatric disturbances such as depression, psychological care for alexithymic features may be required for organ transplantations to proceed smoothly. Consequently, it is necessary to reconsider psychodynamic aspects, especially anxiety concerning organ transplantations. PMID- 8511228 TI - Anorexia nervosa and Turner's syndrome. AB - Publications about Turner's syndrome and anorexia nervosa are extremely rare. All of them, including a new case, are listed up and discussed under psychodynamic aspects. The conclusions drawn from these 21 cases might be essential for genetic counseling, hormonal treatment and psychotherapy in Turner's syndrome. (1) There is a connection between the beginning of the hormonal treatment and the onset of anorexia nervosa in Turner's syndrome. The anxiety during hormonal treatment is due to sexual feelings and the confrontation with the gender role. As the manifestation of anorexia nervosa ought to be taken into account the beginning of a hormonal treatment should be decided in individual context. (2) The early childhood of girls with Turner's syndrome is striking with respect to psychosocial constellations. Short stature and other deficits mean narcissistic wounds. Therefore understanding and affectionate parents are most important to them as they particularly suffer from conflicts with the family. PMID- 8511229 TI - Idiopathic catatonia: validity of the concept. AB - Although catatonic features can be seen in various psychiatric and organic disorders, some patients with catatonia cannot be fitted into existing classification systems. In the current study various sociodemographic and clinical variables were compared between patients who presented with catatonia only (idiopathic catatonia), or with catatonia as a symptom of an identifiable underlying functional disorder. Patients seen over one year (1988) were classified into idiopathic catatonia (n = 30) and according to diagnosis (n = 35; schizophrenia n = 19, depression n = 16). There was an excess of females in the idiopathic group and the illness was of a shorter duration. There were no other differences between the groups. All subjects showed good response to ECTs and required almost the same mean number of ECTs. No clusters were observed using the average method. The current study suggests that catatonic symptoms can occur in the absence of any other identifiable psychiatric syndrome, although they cannot be otherwise differentiated from other psychiatric syndromes in which catatonia can present. PMID- 8511230 TI - Relationships between electrodermal activity and symptomatology in schizophrenia. AB - The present report studies the differences between schizophrenic responders and nonresponders within the different symptomatologic groups of the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). The relationship between the different electrodermal activity parameters and the scores on the scales was also analyzed. The results showed that nonresponders had negative symptoms. In addition negative symptoms registered a general fall in all electrodermal-activity parameters. PMID- 8511231 TI - Cognitive function in the affective disorders: a prospective study. AB - A prospective, controlled study of 50 subjects confirmed claims that major depression or mania may cause temporary disorders of attention, memory, visuo spatial function, and choice reaction time, and cause-independently of medication the appearance of glabellar tap, positive hand-face test, nuchocephalic reflex, and graphesthesia. On follow-up, all these phenomena either disappeared or markedly improved. Age and age of onset, but not pre-morbid intelligence or history of ECT, seemed to modulate the severity of the cognitive impairment. Presence of delusions predicted poor (but reversible) visuo-spatial function. Cognitive impairment accompanied by reversible soft neurological signs was more marked but patients thus affected surprisingly showed lower depressive scores; this was interpreted as representing a secondary, 'organic' form of affective disorder (i.e. a behavioural phenocopy of depression) characterised by a reduced capacity to experience depressive symptoms and by little improvement at follow up. PMID- 8511232 TI - Health service or health insurance. PMID- 8511233 TI - Mergers and consortia. PMID- 8511234 TI - Unemployment and health: a review. AB - Unemployment has an adverse effect on health. This effect is still demonstrable when social class, poverty, age and pre-existing morbidity are adjusted for. Unemployed men and their families have increased mortality experience, particularly from suicide and lung cancer. Unemployed men also have a reduction in psychological well-being with a greater incidence of parasuicide, depression and anxiety. Unemployed men are more likely to use general practitioner and hospital services and receive more prescribed medicines. Smoking and alcohol consumption are often increased after the onset of unemployment. Women are less affected by enforced unemployment, but families are put at greater risk of physical illness, psychological stress and family breakdown. Maintaining financial security, providing proactive health care and retraining for re employment can all reduce the impact of unemployment on health. PMID- 8511235 TI - Asthma-related hospital use among Finnish asthmatics of working age. AB - The aim was to examine asthma-related use of hospital services among persons of working age (15-64 years) in Finland on the basis of hospital discharge registers over a period of 15 years. A total of 155,080 asthma-induced treatment periods and 1,270,453 hospitalisation days were observed in the working-age population during the period concerned. Although the use of hospital services was found to be smallest in the second youngest male age-group (25-34 years), the numbers of treatment periods and hospitalisation days observed among men relative to population were found to increase by age. Middle-aged (35-44) female asthmatics tend to use hospital services more often than men of the same age, but no difference was observed between the sexes in the oldest age-group (55-64 years). The long-term monitoring and guidance of asthmatics and the specialist services required should be coordinated within the basic health care system as in the case of other chronic diseases. The long-term monitoring of asthmatics should be performed by general practitioners, and in the light of the present findings special emphasis should be placed on subjects aged 35 years and older. PMID- 8511236 TI - Severity of sickness at admission to hospital in Colchester 1985 and 1990. AB - In 1991 concern was expressed by hospital physicians and general practitioners about hospital services in Colchester, Essex, following a period of declining real resources. One focus of complaints was that over a period of about five years it had become increasingly difficult to admit acutely ill medical patients. We wished to obtain some objective data to corroborate or refute this anecdotal evidence. We therefore studied the severity of illness at admission in a random sample of emergency admissions for acute chest problems in 1985 and 1990. The main finding was that APACHEII scores were significantly higher (P = 0.002) in the 1990 sample than in the 1985 sample. These objective data contributed to a decision to allocate pounds 100,000 extra funding to the acute medical service in 1991-92. PMID- 8511237 TI - The difficulties of investigating motor vehicle traffic accident mortality in a district. AB - Many difficulties were experienced in obtaining and using data required to test a series of proposed hypotheses to explain the high standardised mortality ratio (SMR) for motor vehicle traffic accidents (MVTAs) in the Bath District. The authors had expected that, given the importance of MVTAs and the amount of effort put into collecting data by established organisations, it should have been possible to access easily the information required to investigate a district which had a high SMR. The variety of data, collected by the many organisations involved in the problem of road traffic accidents, was expected to assist the investigation. However, in practice the result of the difficulties was that the considerable data collected on MVTAs were not readily usable in the district based investigation described in this paper. Organisational and definitional reasons are identified to explain the observed difficulties. Several possible solutions are proposed. The responsibility for MVTA prevention should be with a single named authority which could be either the County Council or the District Health Authority. Systems should be organised to allow each district to access easily the statistics relating to accidents involving residents of the district, especially those occurring outside the district of residence. Results of coroners' investigations should also be routinely transferred to the coroner of the district of residence so that information on deaths to all residents of a district can be obtained from a single local source. Given the existing systems and limited resources, the authors concluded that further investigation into the high SMR for MVTAs in the Bath Health District was not justified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511238 TI - Women's views of the Scottish Breast Screening Programme: a national consumer opinion survey. AB - A questionnaire survey of 3,000 women attending operative Scottish breast screening outlets was conducted to ascertain women's views of the Scottish Breast Screening Programme. The survey aimed to discover women's opinions of waiting areas, staff, changing facilities, screening procedure and intentions about returning for screening in the future. The response rate was 86%. Overall 84% found reception staff very helpful, 98% found undressing instructions clear, waiting areas comfortable and changing areas private enough; 77% thought the radiographers were very understanding; 97% received enough explanation about the mammogram and 96% felt able to ask questions; 89% said the entire screening process was as, or better than expected; 89% said they were very likely to come back in three years' time. At individual outlets up to 33% of women had insufficient information about breast screening prior to attending and up to 17% had to wait more than 20 minutes after their appointment times. Up to 21% felt moderate or severe pain on screening and up to 51% found pressure worse than expected. In conclusion, the Scottish Breast Screening Programme is very acceptable to women but at some outlets the appointments system, information giving and screening pressure needs to be reviewed. PMID- 8511239 TI - Enteric fever in Scotland 1975-1990. AB - In the 16-year period 1975-90, there were 267 cases of acute infection with typhoidal salmonellae reported in Scotland, in addition to which 32 chronic carriers were identified. The overall incidence of disease changed little over this period, but there was a fall in indigenously acquired paratyphoid B and typhoid, and a rise in imported paratyphoid A. The majority, 215 (81%), had a history of recent travel and were considered to have acquired infection overseas. Only six of the indigenously acquired infections were traced to acutely infected persons, illustrating the low risk of transmission associated with acute enteric fever in the UK. Only one death was definitely ascribed to enteric fever, and one person with S. paratyphi B became a chronic carrier. Significant illness was observed in five chronically infected individuals, including one with carcinoma of the gallbladder. UK residents of 'Asian' ethnicity returning from the Indian subcontinent accounted for 63 (46%) of the 137 cases of typhoid, and 34 (64%) of the 53 cases of paratyphoid A. People of 'Asian' ethnicity were more likely to have acquired infection overseas than 'non-Asians': 110 (89%) of 123 persons compared with 105 (73%) of 144 (odds ratio 3.1, 95% confidence interval 1.5-6.6, P = 0.001). Although there seems to be limited scope for preventing indigenously acquired infection, immunisation of travellers could contribute significantly to reducing the incidence of typhoid. PMID- 8511240 TI - Compulsory removal to and detention in hospital in the case of notifiable disease: a survey of public health doctors. AB - Compulsory detention of an individual in hospital, because they have a notifiable disease, is controversial. Difficulties experienced by the authors in applying Sections 37 and 38 of the Public Health (Control of Disease) Act 1984 led them to conduct a postal survey of the experience of Consultants in Communicable Disease Control/Medical Officers of Environmental Health (CCDC/MOEH) currently in post in England. Out of 138 respondents (80% response rate), 48 respondents (34.8%) had dealt with 'non-compliant' individuals posing an infectious risk to the community. Of the 48, 13 respondents achieved compliance by threatening to use Section 37/38 and only 6 respondents resorted to using Section 37/38, equivalent to less than one use of the sections for every hundred years of CCDC/MOEH experience. In most cases the notifiable disease in question was tuberculosis. In contrast to our experience and previously reported cases, the survey suggests generally satisfactory experience of Section 37/38 amongst CCDC/MOEH currently in post. Recommended guidelines for the use of Section 37/38 are given. PMID- 8511241 TI - Incarceration history as a risk factor for HIV infection among Puerto Rican injection drug users. AB - This study assesses factors associated with incarceration history and HIV seropositivity among 1,700 out-of-treatment drug injectors recruited in Puerto Rico between 1989-1990 from health care centers, emergency rooms, copping areas, shooting galleries, bars, billiard rooms and street corners. Analysis links incarceration history with criminal involvement and chronic drug use. After controlling for sociodemographics and previously reported correlates of HIV status, regression analysis shows incarceration history significantly relates to HIV status. The only predictor of incarceration history not related to HIV status was illegal activity as a major source of income. Analysis emphasizes HIV prevention programs within the penal system. PMID- 8511242 TI - Human immunodeficiency virus infection and risk behaviors among injection drug users in four Puerto Rican communities. AB - This study compares the prevalence of human immunodeficiency virus (HIV) infection and HIV risk behaviors among 1,702 injection drug users (IDUs) recruited within four catchment areas in metropolitan San Juan (79.9% male and 20.1% female). To assess the impact of different antecedent variables on intercommunity risk differences, we constructed separate logistic regression models for each one of the catchment areas in the analysis. Old San Juan/Santurce has the highest rate of HIV seropositivity. Furthermore, Old San Juan/Santurce IDUs were more likely to have had incarceration experience, to report using drugs only by injection, and to have been injecting drugs for 16 years or more. Also, this group was more likely to report practicing prostitution and to have been diagnosed with sexually transmitted diseases (STDs) than their peers from the other sites. The need of preventive programs in specific communities within metropolitan urban areas is discussed. PMID- 8511243 TI - Effects of a HIV risk reduction education program among injection drug users in Puerto Rico. AB - This report examines the extent to which an educational component enhanced the efficacy of a community outreach program in reducing HIV transmission behaviors among injecting drug users (IDUs). The experimental enhancement comprised three group educational sessions where detailed information on HIV risk and protective behaviors was conveyed, protective behaviors were shown and practiced, and a problem solving perspective guided discussion of serostatus results. Substantial risk reduction in behaviors were prospectively measured. However, IDUs assigned on a random basis to the enhanced intervention showed no significant differences in levels of risk reduction when compared to those assigned to the standard-only intervention. The chronic and intensive use of injected drugs among the IDUs studied and their high level of HIV infection suggest the need of interventions geared to maximize the utilization of health care services and enhance the supportive functions of familial and social networks of IDUs. PMID- 8511244 TI - Preservation of Nocardia sp. cultures on porous beads. AB - Coating of sterile glass beads with certain bacteria has provided a simple method for their low temperature storage. This procedure was applied to Nocardia sp., filamentous bacteria which are maintained by subculture on Sabouraud dextrose agar especially in clinical laboratories. The coating of glass beads by Nocardia sp. resulted in an easy and effective method to preserve the microorganisms at 76 degrees C. PMID- 8511245 TI - Pathology of pulmonary hypertension and schistosomiasis mansoni. AB - We report a case of a 33-year-old woman with grade IV pulmonary hypertension and end stage cor pulmonale secondary to chronic schistosomiasis (bilharziasis). The pathophysiology and morphologic features are discussed. Schistosomiasis is an important etiology to consider in the differential diagnosis of pulmonary hypertension. PMID- 8511246 TI - [Brief history of AIDS in non-human primates and its contribution to the study of acquired immunodeficiency syndrome]. AB - Infection of the rhesus monkey (Macaca mulatta) with retroviruses originating from African non human primates (SIV) induces in this species an acquired immunodeficiency syndrome (SAIDS) closely resembling AIDS in humans. Analogies between the SIV-rhesus system and AIDS in humans are described in this work, analyzing the close relationship existing between the HIV and SIV viruses, and the similarities between SIV disease in the rhesus and HIV disease in humans. A review of current advances in AIDS vaccine research, using the SIV-rhesus model, is also included. PMID- 8511247 TI - Drugs and AIDS. PMID- 8511248 TI - [Guidelines for the management of women with HIV infection]. AB - During the second decade of AIDS the spread of this disease has encompassed most areas of the world. In Puerto Rico the epidemic has been different than in the mainland USA. Our initial cases were mostly associated to intravenous drug use and subsequently heterosexual transmission. Sexual transmission of HIV is the principal cause of AIDS for women in Puerto Rico. AIDS is also the principal cause of death in young women in Puerto Rico (ages 25-40). Therefore the counselling to women has to include the universality of the risk. Data from seroprevalence studies show a high prenatal seroprevalence (1%) in the San Juan Metropolitan Health Region. In view of the high prenatal seroprevalence, universal offering of HIV counselling and testing is recommended. Gynecologic evaluation is essential in the follow-up of women with HIV infection and should include frequent evaluations to determine the frequent occurrence of premalignant lesions in the cervix that may be associated to immunosuppression. PMID- 8511249 TI - [Acceptance to the incorporation of liberal arts in the curriculum of the Medical School at the University of Puerto Rico]. AB - The acceptance of incorporating courses in liberal arts to the present curriculum of the School of Medicine was assessed. A survey was suministred to 400 subjects that belonged to academic and professional fields of medicine. The results from the survey showed that those who played an acting role in the current curriculum were receptive to innovations. The professors of the clinical aspect of medicine and the practicing physicians were more receptive to curricular change. First year medical students were more receptive than seniors. This positive view constitutes a strong argument for eliciting curricular creativity. These results allow future changes around the medical education of the University of Puerto Rico School of Medicine. PMID- 8511251 TI - Cocaine induced myocardial ischemia. AB - We report a case of myocardial ischemia induced by cocaine. The ischemia probably induced by coronary artery spasm was reversed by nitroglycerin and calcium blocking agents. PMID- 8511250 TI - HIV risk behaviors and HIV seropositivity among young injection drug users. AB - Although injection drug use (IDU) is the major risk category for HIV infection in Puerto Rico and injection drug users start their drug injection careers very young, there is little information related to drug injection patterns of young IDUs. In this paper we report on factors found to be associated with HIV seropositivity among 255 young IDUs (16-24 years old). Overall, 23.5% subjects were HIV seropositive. Being 22 to 24 years old, having dropped out of school, having a history of incarceration, and having been diagnosed with STDs, and initiating drug use injection before 17 years of age were the factors significantly related to HIV seropositivity. Findings suggest that prevention programs should begin early in the development of youngsters. Special HIV and STD preventive programs for youngsters at risk of leaving school before completing high school should be a priority. PMID- 8511252 TI - Dental health care--can it be provided to all? PMID- 8511253 TI - An improved technique for Class V composite resin inlays. AB - Treatment of cervical carious lesions presents significant problems to the restorative dentist, including difficulties with access and with the restorative materials themselves. Conventional approaches are not suitable for inaccessible or multisurface cervical lesions. Polymerization shrinkage associated with composite resins is also a problem. Although indirect composite resin inlay techniques address these shortcomings, they generally require two patient visits. An improved technique solves these problems by utilizing a copper band impression technique, a quick-setting stone die, extraoral curing of the composite resin inlay, and dentinal adhesive bonding technology in a one-visit restorative approach to the cervical carious lesion. PMID- 8511254 TI - Biodegradable dressing material used in guided tissue regeneration of periodontal tissues: a case report. PMID- 8511255 TI - A new method of attaching cast gold occlusal surfaces to acrylic resin denture teeth. AB - Historically, cast gold occlusal surfaces for complete or removable partial dentures have been fabricated with retentive loops or beads and luted to prepared denture teeth with acrylic resin or attached to tooth-colored, heat-processed acrylic resin. At present, alternatives to mechanical retention for attaching resin to metal include chemical bonding of the resin after placement of intermediate ceramic or tin layers and the use of chemically adhesive resin cements. Compared to mechanical retention, the chemical bonding of resin to metal requires less gold and allows more room for properly contoured and esthetic resin. Additionally, this chemical bond limits microleakage at the resin-metal interface. In the following technique, cast gold occlusal surfaces are fitted to onlay preparations of acrylic resin denture teeth set in a processed denture base. The castings are air-abraded, tin plated, and luted to the denture teeth with Panavia dental adhesive. This method is quick, easy, and economical. PMID- 8511256 TI - Hydrocolloid impressions of multirooted teeth: a clinical report. AB - An indirect technique for taking hydrocolloid impressions of multirooted teeth is described. Advantages of both hydrocolloid impression material and the technique are discussed. PMID- 8511257 TI - Characterization of enamel exposed to 10% carbamide peroxide bleaching agents. AB - The purpose of this investigation was to evaluate the effect of three 10% carbamide peroxide bleaching agents on enamel microhardness and surface morphology. Seventy-two enamel slabs were subjected to one of three carbamide peroxide solutions or an artificial saliva solution for 15 hours a day for 2- and 4-week periods. During the remaining 9 hours, slabs were exposed to human saliva in vivo. Although differences were not statistically significant, microhardness values of all treated specimens 2 weeks after treatment were less than those of control specimens. These trends, however, were not evident at 4 weeks. Scanning electron microscopic evaluation revealed significant surface alterations in enamel topography for slabs treated with the bleaching solutions for 4 weeks. The most severe alterations were found in slabs exposed to the lower-pH solutions. PMID- 8511258 TI - Dental health patterns in an urban Midsouth population: race, sex and age changes. AB - Little is known about the oral health of American blacks. In particular, have they experienced the same reductions in dental caries and improvements in oral health as has the majority culture during the past several decades? A contemporary series of patient records (n = 300) was examined to test for age, sex, and race (American black and white) differences in an urban Midsouth population. Tooth loss was strongly age progressive in blacks and whites, but the rate was much greater in blacks. Periodontal probing depths also tended to be greater in blacks, particularly for the maxillary anterior teeth. The pattern of tooth loss with age in blacks is similar to rates recorded for the whole United States in the early 1960s. Subsequently, whites have tended to experience substantial improvements in oral health (ie, fewer decayed, missing, and filled teeth and less tooth loss); blacks in this sample have not exhibited this improvement. PMID- 8511259 TI - Evaluation of a new dentinal bonding system. AB - The purpose of this study was to compare the in vitro microleakage of a new dentinal bonding system, not yet released in the United States, to the microleakage of two first-generation bonding agents. Simulated Class V cavities were prepared in freshly extracted bovine incisors and restored with the appropriate composite resin-bonding agent combination. Restorations were thermocycled and examined for microleakage at 24 hours and 60 days. Comparison of the materials revealed no statistically significant difference in microleakage scores at the gingival or incisal margins after 24 hours. However, the first generation bonding agents exhibited significantly more microleakage at the gingival margin than did the new bonding system after 60 days. No significant increase in microleakage was measured at the incisal margin for any of the materials after 60 days. In contrast, all materials exhibited a significant increase in leakage at the gingival margin after 60 days. No correlation between microleakage and polymerization shrinkage or coefficients of thermal expansion of the composite resins could be established. PMID- 8511260 TI - Extending the use of rubber dam isolation: alternative procedures. Part II. AB - This paper, in three parts, describes additional modified rubber dam utilizations that are generally not attempted with restrictive orthodox application methods. Part II covers alternative means of retention, with the emphasis on nuisance-free and easy application, during the preparatory, impression, and cementation phases of cast restorations. PMID- 8511261 TI - Light-hardened Class I glass-ionomer-resin cement restoration of a permanent molar. AB - Clinical experiences with light-hardened glass-ionomer-resin restorative cement indicate that it has improved properties compared to self-hardening glass-ionomer cements. Wear resistance and other material strengths are improved so that the material can be considered for conservative Class I restorations in permanent teeth. This article details occlusal restoration of a permanent molar with one light-hardened glass-ionomer-resin cement and discusses the potential for such restorations. PMID- 8511262 TI - The use of composite resins in combination with anchorage posts as core material in endodontically treated teeth: clinical aspects of the technique. AB - In vitro tests and a clinical examination of 51 patients who were treated over a period of 12 years have demonstrated that a composite resin core that is surrounded by a gold crown may provide the same function and strength as a conventional gold core. However, the method demands a thorough knowledge of the materials and a careful and detailed technique. The importance of an initially effective dentinal bond to the chosen hybrid composite resin is stressed. Zinc phosphate cements and the technique of cementing are also discussed. In most cases, a damaged root will have to be reinforced with a post, and the author recommends the use of a threaded titanium post that fits well and is bound to the root with a so-called passive cementation technique. The author has also had positive experiences with composite resin crowns, which can be expected to have a functional life of at least 10 years. PMID- 8511263 TI - The applicability of osseointegrated implants in the treatment of partially edentulous patients: three-year results of a prospective multicenter study. AB - Nine clinical centers using the Branemark System participated in a prospective study of 159 partially edentulous patients between 18 and 70 years of age. Clinical parameters evaluated were Plaque Index, gingivitis, pocket depth, Bleeding Index, tooth mobility, prosthesis stability, and stomatognathic function. Change in bone height around fixtures was measured radiographically. After 3 years, 460 loaded fixtures, supporting 174 prostheses in 139 patients, remain in the study. The complications, failures, and technical problems are presented. After 3 years of this 5-year study, results suggest that implant-based treatment of partially edentulous patients may achieve a success rate comparable to that obtained in edentulous patients. PMID- 8511264 TI - A 2-year clinical evaluation of two pit and fissure sealants placed with and without the use of a bonding agent. AB - The purpose of the study was to evaluate whether the clinical effectiveness of pit and fissure sealant was increased (as demonstrated by an increased retention rate) when a bonding agent was used prior to the placement of the sealant. Two pit and fissure sealants, Concise Light Cured White Sealant and Prisma Shield Light Cured Sealant, were placed in vivo with and without the use of the bonding agents, Scotchbond 2 and Prisma Universal Bond. After 2 years, 55% of the sample was available for recall. The retention rates for the sealants were 77% for Concise with Scotchbond 2, 84% for Concise with no bonding agent, 77% for Prisma Shield with Universal Bond, and 77% for Prisma Shield with no bonding agent. Results of this study indicated that the use of a bonding agent prior to the application of a pit and fissure sealant does not increase the retention rate. PMID- 8511265 TI - Clinical diagnosis and treatment of endodontic and periodontal lesions. AB - Because of the intimate relationship of the root canal system and the periodontium, developing endodontic and periodontal lesions may mimic each other in clinical and radiographic appearance. The etiology, diagnosis, treatment, and prognosis of endodontic and periodontal lesions will be discussed. PMID- 8511266 TI - The efficacy of Plax prebrushing rinse: a review of the literature. AB - Removal of bacterial plaque is a prerequisite to the prevention and control of periodontal disease. In highly motivated patients, it is possible to control plaque successfully by mechanical means. Because most patients lack sufficient motivation and skill to perform effective plaque control on a regular basis, use of antimicrobial chemical agents is essential to gingival health. In 1985, Plax, a prebrushing oral rinse, was introduced. The manufacturer claims that the solution acts as a detergent that removes some bacterial plaque and loosens the remainder for easy removal by toothbrushing. A review of current dental research related to this claim is presented. The data provided do not support the use of Plax dental rinse as part of an oral hygiene program. PMID- 8511267 TI - The golden age of teaching--over for some, here to stay for those who care. PMID- 8511268 TI - Replacement of a fractured incisor fragment over pulpal exposure: a case report. AB - This paper is a clinical report demonstrating reattachment of a fractured incisor fragment. The fragment was replaced without the use of a filled composite resin, because the fracture had little splintering of the edges of the opposing pieces. Frank pulpal exposure was treated by an acid-etching procedure, wet bonding and surface disinfection prior to sealing of the wound site. At 1 year, the tooth is vital and has remained totally asymptomatic. PMID- 8511269 TI - Coronal fracture with invasion of the biologic width: a case report. AB - To repair a coronal fracture with invasion of the biologic width, flap surgery with osteotomy and osteoplasty localized on the fractured tooth was performed, and the crown was reattached to the tooth remnant with a composite resin system. Results after 6 years revealed optimal periodontal health and reasonable esthetics. PMID- 8511270 TI - Tunnel restorations versus class II restorations for small proximal lesions: a comparison of tooth strengths. AB - An increased emphasis on the preservation of tooth structure has led to alternative cavity designs for early proximal caries. The tunnel restoration (which preserves the marginal ridge) and a conservative Class II composite resin restoration were compared in vitro for effects on tooth strength with nondestructive and destructive tests. The tunnel restoration, which is generally thought to be the more conservative of the two techniques, was actually more damaging, as shown by the stiffness, load at fracture, and proximity to the pulp. PMID- 8511271 TI - Clinical placement of modern glass-ionomer cements. AB - The main advantages of glass-ionomer cement are its ionic exchange with dentin and enamel and its continuous fluoride release, which acts as an effective anticariogenic agent. The new dual-curing (light-activated) cements have enhanced physical properties and excellent esthetics, so the situations in which they can be placed as a complete restoration are greatly increased. If the occlusal load is too great to use glass-ionomer cement alone, the dual-curing cements are ideal for the lamination technique, in which the cement is used as a dentinal substitute and is covered with composite resin. This paper discusses the clinical placement techniques required to ensure success with either technique. PMID- 8511272 TI - The strange world of research and congresses. PMID- 8511273 TI - A removable appliance to extrude teeth. AB - A simple removable appliance to effect minor tooth extrusion of anterior teeth is described and its use is illustrated. This technique uses a labial bow in conjunction with a composite resin button bonded to the labial surface of the tooth or teeth to be extruded. PMID- 8511274 TI - Gingival fibromatosis: study of three generations with consanguinity. AB - Familial gingival fibromatosis affecting six members among three generations of an Islamic family is reported. Clinical findings are reported and the inheritance pattern is discussed. Histopathologic examination of the excised tissue revealed mainly fibroblasts with prominent, rough-surfaced endoplasmic reticulum. Cells with vesicular nuclei, resembling mast cells, were also observed. PMID- 8511275 TI - Electronic dental anesthesia: a pilot study. AB - Electronic dental anesthesia uses the Gate Control Theory of transcutaneous electrical nerve stimulation. The battery-controlled Ultracalm electronic dental anesthesia unit is a noninvasive procedure to electrically block pain transmissions in dental patients. This pilot study to test the efficacy of electronic dental anesthesia for simple restorative procedures was subjectively reported by 20 patients who had never been exposed to this type of anesthesia. None of the patients indicated the procedure was uncomfortable, and 14 of 20 subjects indicated that they preferred electronic dental anesthesia to local anesthetic injection. Electronic dental anesthesia appears to be an effective means of obtaining local anesthesia for certain dental procedures. PMID- 8511276 TI - Prevention of infective endocarditis: an update for clinicians. American Heart Association. AB - Infective endocarditis is a rare, serious, and sometimes fatal heart disease that can be caused by bacteremia from the mouth, especially by Streptococcus viridans. As a result, dental procedures have often been blamed for cases of infective endocarditis but poor oral health and hygiene may actually cause more cases of infective endocarditis than do dental procedures. The American Heart Association and other groups have published recommendations for the prevention of infective endocarditis in dental patients and advise specific antibiotic regimens for certain dental procedures in cardiac-abnormal patients. The most recent (1990) American Heart Association recommendations are the most conservative yet, reflecting concern about the prevention of not only infective endocarditis, but also problems resulting from the antibiotics themselves. Clinicians should carefully consider not only the patient's medical history, but also the types of dental procedures planned. PMID- 8511277 TI - Clinical application of a cantilevered adhesive prosthesis: a case report. AB - A cantilevered adhesive prosthesis was designed for a patient whose maxillary right central incisor was extracted. The width of the edentulous space was much greater than the mesiodistal width of the lost tooth, impeding the construction of a conventional fixed partial denture. A much more conservative and esthetic result was achieved by the construction of a cantilevered adhesive prosthesis in which the extracted tooth was used as a pontic. PMID- 8511278 TI - Radiation dosage of a dental imaging system. AB - This study compared the radiation dosage necessary for obtaining clinically acceptable images with a new dental imaging system (radiovisiography) to that required with a conventional-film radiographic technique. Results showed that radiovisiography required significantly less radiation exposure, only 22.3% of that used in the conventional technique. Problems, such as lack of flexibility and the limited size of the x-ray-sensitive surface, are associated with radiovisiography; however, the system effectively complements conventional-film radiography. PMID- 8511279 TI - The influence of lining techniques on the marginal seal of Class II composite resin restorations. AB - Various sealing techniques using a light-curing dental adhesive (Scotchbond 2) and bulk application of a light-curing resin-bonded ceramic were examined in 203 Class II cavities. Different pretreatment procedures and lining materials were used, and in one series resin impregnation of the contraction gap was included. The presence of gaps or leakage was disclosed either by a dye or a fluorescent resin penetration technique. In many restorations, Scotchbond 2 and a light curing glass-ionomer lining did not prevent gap formation at the cervical wall. The gap usually occurred between the liner and the dentin, with dye penetration into the dentin. Three liners, one containing polytrifluorethylene sodium fluoride and calcium fluoride, one containing polyamide resin, and one containing calcium hydroxide, did not prevent dye penetration to the dentin at all; good dentinal protection was frequently observed, however, in cavities treated with a hydrophilic shellac film prior to placement of a polystyrene liner. The best results were observed when dentinal treatment with this lining system was followed by resin impregnation of the contraction gap after the composite resin had set. PMID- 8511280 TI - Fracture resistance of amalgam and composite resin cores retained by various intradentinal retentive features. AB - The fracture strengths of amalgam and composite resin cores retained by three types of intradentinal retentive features were compared with the fracture strength of cores retained by four self-threaded retentive pins. Composite resin cores had significantly greater resistance to fracture than amalgam cores with any of the retentive features. The fracture strength of amalgam cores retained by retentive pins was comparable to that of amalgam cores retained by a post with a countersink, but significantly higher than the strength of those retained by slots or channels. The fracture strength of composite resin cores retained by retentive pins was significantly higher than that of composite resin cores retained by any of the alternative intradentinal retentive features. PMID- 8511281 TI - Validation of tagging with MR imaging to estimate material deformation. AB - Myocardial tagging with magnetic resonance imaging is useful for non-invasive estimation of in vivo heart wall deformation. To validate the method of strain estimation and quantify the error of deformation estimates, a deformable silicone gel phantom in the shape of a cylindrical anulus was built and imaged. Four observers digitized the displacement of magnetic tags in two deformation modes: axial shear, caused by a 45 degrees rotation of the inner cylinder, and azimuthal shear, caused by a 13.5-mm longitudinal translation of the inner cylinder. In axial shear, good agreement was found between the angular displacement of stripes painted on the gel and an analytic solution. Displacement of magnetic tags also agreed with that solution. Interobserver and observer-model errors in deformation estimates were quantified for homogeneous and nonhomogeneous strain analysis. In homogeneous strain analysis, errors in point localization produced relatively large errors, which were reduced in nonhomogeneous strain analysis. Both estimates were unbiased across the range of deformations. PMID- 8511282 TI - Hearts with twisted atrioventricular connections: findings at MR imaging. AB - The "crisscross" heart and the heart with "superoinferior ventricles" are closely related congenital cardiac malformations that are characterized by twisted atrioventricular connections. The authors studied the morphologic characteristics of three hearts with twisted atrioventricular connections as seen on magnetic resonance (MR) images. The most important clue to the diagnosis was the distorted atrioventricular connections that were demonstrated on serial images. The axes of the atrioventricular connections through the atrioventricular valves were not parallel to each other. The presence of unusual recesses in the cardiac chambers, the angulated or curved configuration of the atrial and ventricular septa, and the unexpected great arterial relationship for the given combination of segmental connections supported the findings of twisted atrioventricular connections. MR imaging facilitated the precise morphologic diagnosis of these hearts. PMID- 8511283 TI - X-ray contrast media: where are we now, and where are we going? AB - The U.S. market for x-ray contrast media (XCM) has grown from $103,000,000 in 1985 to approximately +f41 billion today. The increase in market size represents a moderate increase in number of procedures (5% to 7% per year) and a large increase in the cost per milliliter of solution. The number of XCM available continues to increase, and three are currently in clinical trials in the United States. Clinically significant increases in either efficacy or safety are unlikely with these agents; however, increased competition may cause some slight erosion in the price per milliliter. The development of new XCM focuses on strategies to target different distribution spaces and new or simplified syntheses. PMID- 8511284 TI - Levator palpebrae superioris muscle: MR evaluation of enlargement as a cause of upper eyelid retraction in Graves disease. AB - Sympathetic stimulation of the Muller muscle may be responsible for most of the medically reversible cases of eyelid retraction in patients with Graves disease. The authors studied 21 patients with class I Graves ophthalmopathy (GO), 32 patients with Graves disease without ophthalmopathy (GD), and 12 control subjects. T1-weighted spin-echo magnetic resonance (MR) imaging was performed with a 0.5-T superconducting system. The thickness of the levator palpebrae superioris muscle was determined from sagittal MR images. The thickness of the levator muscles in patients with GD did not differ from the thickness in control subjects, but the levator muscles in patients with GO were significantly thickened (P < .01). The thickness of the levator muscles in patients with GO was significantly greater than in those of patients with GD (P < .01). In 64 orbits of patients with GD, 3% of levator muscles were thickened. In 33 of 40 (83%) orbits of patients with GO presenting with upper eyelid retraction, the levator muscles were thickened. Sagittal MR imaging demonstrated thickening of the levator muscles in patients with persistent upper eyelid retraction. The authors conclude that a thickened levator muscle probably causes upper eyelid retraction in patients with GO. PMID- 8511285 TI - Functional mapping of activated human primary cortex with a clinical MR imaging system. AB - Functional activation of the human brain can be visualized with magnetic resonance (MR) imaging, but most studies so far have used echo-planar imaging or magnetic fields of 2 T and above, neither of which are at present widely available. The authors used a standard 1.5-T MR imaging system to map regions of the brain that are activated with visual and motor tasks, using a long echo time (60 msec) fast low-angle shot sequence. Eleven visual and 14 motor studies were performed, and activation was seen in all cases. Up to 15% signal intensity change was apparent in gray matter but not in white matter. The precise anatomic location and extent of activation were defined by reference to T1-weighted images acquired during the same examination. This method of relating brain structure to function uses equipment that is widely available, which has considerable implications for the investigation of many neurologic and neurosurgical diseases and for our understanding of brain function and dysfunction. PMID- 8511286 TI - Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve. AB - The authors have developed a technique to estimate input functions from a population-based arterial blood curve in positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose (FDG). A standardized pump injection was used in 34 subjects. A population-based blood curve was generated based on the first 10 subjects. In the remaining 24 subjects, an estimated input function (EIFa) was obtained by scaling the population-based curve with two arterial blood samples, one obtained at 10 minutes and the other at 45. Time integrals for EIFa and the real arterial input function (RIF) were in excellent agreement (r = .998, P < .0001). Cerebral metabolic rates for glucose calculated with EIFa and RIF and the autoradiographic method also correlated excellently (r = .992, P < .0001). Analogous correlations were achieved with arterialized venous samples as scaling factors. These results suggest that individually scaled, population-derived input functions may serve as an adequate alternative to continuous arterial blood sampling in quantitative FDG-PET imaging. PMID- 8511287 TI - Cerebral blood flow velocity after head injury: transcranial Doppler evaluation. Work in progress. AB - To study blood flow velocity (BFV) changes, serial transcranial Doppler ultrasound (US) examinations of basal cerebral arteries were performed in 47 patients with head injury. Computed tomographic (CT) scans obtained at admission were analyzed for the presence of intracranial hemorrhages. Glasgow Coma Scale scores were obtained at admission in 46 patients. The prevalence of posttraumatic increased BFV was 77% (n = 36). Two groups of patients were identified according to the time of onset of increased BFV. They differed with respect to duration and severity of changes, Glasgow Coma Scale score, and evidence of intracranial hemorrhagic lesions. Low Glasgow Coma Scale scores were predictive of increased BFV within 72 hours after injury (P < .001). Patients with hemorrhages were significantly more prone to experience increased BFV within 72 hours (P < .05); 34% of patients who did not have hemorrhage, however, developed increased BFV. Increased BFV after head trauma is not uniformly found and cannot be explained by one pathologic mechanism. PMID- 8511288 TI - Cerebellar and spinal hemangioblastomas: evaluation with intraoperative gray scale color Doppler flow US. AB - Intraoperative gray-scale and color Doppler flow ultrasound (US) studies were performed in 12 patients with von Hippel-Lindau disease during surgical excision of hemangioblastomas. There were a total of 21 lesions: two were in the cerebellum and 19 were in the spinal cord. Twelve of the 19 spinal hemangioblastomas were hyperechoic to the spinal cord and thus were easily detected with gray-scale US. Color Doppler flow images provided improved delineation of all lesions compared with the images produced with standard gray scale US. Seven of the 19 spinal lesions were detected only with color Doppler flow imaging because they were isoechoic to the normal spinal cord at gray-scale US. Color Doppler flow imaging enabled differentiation of the cysts and syrinx cavities associated with hemangioblastomas from dilated intraspinal vascular structures. In all cases, intraoperative color Doppler flow imaging facilitated the localization of hemangioblastomas during the neurosurgical procedure. PMID- 8511289 TI - The conus medullaris: normal US findings throughout childhood. AB - A prospective ultrasound (US) study of children without neurologic or spinal problems or midline cutaneous abnormalities on the back was performed to determine the level of the conus medullaris in healthy children. The tip of the conus was identified in sagittal and transverse planes, and a radiopaque bead was placed on the skin to mark the location of the tip. Findings at subsequent radiography confirmed the vertebral level. A total of 161 children, aged 4 days to 13 years 5 months (mean, 3 years 7 months; median, 3 years 1 month), composed the study population. Conus levels in these healthy children varied from the level of T10-11 interspace to the superior aspect of the L-3 vertebra. However, in only two children were the conus levels below the middle portion of L-2. Estimations of vertebral levels of the conus based on the US scan alone were within one vertebral level of the level determined at radiography in 145 of 161 (90%) cases. Palpable landmarks, the tip of the lowest rib and the iliac crest, corresponded to the level of the L-2 and L-5 vertebrae, respectively. The conus medullaris can be located at US in most children, even beyond infancy. The normal levels are constant throughout childhood. PMID- 8511290 TI - Traumatic atlanto-occipital dislocation in children. AB - During a 5-year period, 11 children were identified as having traumatic atlanto occipital dislocation injury on the basis of clinical and radiographic findings. Radiographic criteria including the distance between the tip of the dens and the basion (DB distance), the BC/OA ratio (ratio of the distance between the basion and the posterior arch of C-1 divided by the distance between the opisthion and the anterior arch of C-1; normal ratio, < 1), and the width of the atlanto occipital joint (normal width, < or = 5 mm) were correlated with clinical presentation and outcome. Normal pediatric values for DB distance were reviewed in a series of 110 lateral cervical spine radiographs. The normal DB distance was 8.3 mm +/- 4.2 (mean +/- 2 standard deviations). All 11 children had DB distances greater than 1.4 cm (mean, 1.7 cm). The BC/OA ratio was greater than 1 in only six patients. Of the 11 children, six died with severe neurologic deficits and five survived with minimal or no neurologic sequela. Without the clinical presentation variable, widened DB distance may be the first abnormality identified to suggest atlanto-occipital injury. PMID- 8511291 TI - Conversion of bone marrow in the humerus, sternum, and clavicle: changes with age on MR images. AB - To study the normal conversion of bone marrow in the humerus, sternum, and clavicle, 101 T1-weighted magnetic resonance (MR) studies obtained in 91 patients aged 2 days to 37 years were retrospectively evaluated. Conversion from hypointense (red) to hyperintense (yellow) bone marrow was assessed by comparison of signal intensity of the bone marrow with that of muscle and fat. Conversion began in the proximal humeral epiphysis (in 16 of 21 adequate studies [76%]), humeral diaphysis (17 of 30 adequate studies [57%]), and distal metaphysis (16 of 25 adequate studies [64%]) before age 1 year and was nearly complete in these regions (20 of 22 adequate studies [91%], 20 of 21 adequate studies [95%], and five of seven adequate studies [71%]) in examinations of children aged 1-5 years. In the proximal humeral metaphysis, conversion was seen in 21 of 22 adequate studies (95%) in children aged 1-5 years and was nearly complete in all by age 20 years. Conversion began in the sternum (six of six studies [100%] in children aged 6-10 years) and clavicle (six of eight studies [75%] in children aged 6-10 years) before age 11 years but was never complete. Bone marrow conversion in the humerus, sternum, and clavicle follows a well-defined pattern and is depicted earlier by MR imaging than one would expect on the basis of histologic data. PMID- 8511292 TI - Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. AB - To determine whether low-osmolality contrast media (LOCM) are less nephrotoxic than high-osmolality contrast media (HOCM), the authors searched MEDLINE and EMBASE databases and other sources to find randomized trials with data collected on changes in glomerular filtration rate or serum creatinine (SCr) level with LOCM and HOCM. Forty-five trials were found. Data were unavailable from 14 trials. When the P values from the other 31 trials were pooled, an overall P value of .02 was found. Among 24 trials with available data, the mean change in SCr was 0.2-6.2 mumol/L less with LOCM than HOCM. Among 25 trials with available data, the pooled odds of a rise in SCr level of more than 44 mumol/L with LOCM was 0.61 (95% confidence interval [CI], 0.48-0.77) times that after HOCM. For patients with existing renal failure, this odds ratio was 0.5 (CI, 0.36-0.68), while it was 0.75 (CI, 0.52-1.1) in patients without prior renal failure. Greater changes in SCr level occurred only in those with existing renal failure and were less common with LOCM (odds ratio, 0.44; CI, 0.26-0.73). Use of LOCM may be beneficial in patients with existing renal failure. PMID- 8511293 TI - Hyperechoic renal tumors: anechoic rim and intratumoral cysts in US differentiation of renal cell carcinoma from angiomyolipoma. AB - To determine whether angiomyolipomas (AMLs) and renal cell carcinomas (RCCs) can be differentiated at ultrasonography (US), the authors retrospectively evaluated the sonographic appearances of 31 AMLs and 38 RCCs. Sonograms were evaluated by three radiologists without knowledge of histologic findings, with respect to the echogenicity of the tumor, predominant echotexture, and whether an anechoic rim was present. All patients had also undergone computed tomography (CT) to check for tumoral fat. Intratumoral fat was evident at CT in 28 of the 31 AMLs. RCCs had no fat at CT or histologic evaluation. An anechoic rim was evident in 32 of 38 (84%) RCCs, and 10 RCCs had small anechoic areas with back echo enhancement, which corresponded to intratumoral cysts or cystic necrosis at histologic evaluation. The anechoic rim and areas indicative of cysts were not found in AMLs. Demonstration of an anechoic rim and/or intratumoral cysts in a hyperechoic mass at US suggests that the tumor is an RCC. PMID- 8511294 TI - Obstetric hemorrhage: prophylactic and emergency arterial catheterization and embolotherapy. AB - The role of arterial catheterization and embolotherapy was evaluated in 18 patients with postpartum hemorrhage or a risk of hemorrhage. Nine patients underwent emergency arterial catheterization for unanticipated postpartum hemorrhage due to uterine and vaginal tears and/or placental abnormalities. Bleeding was controlled with embolization with gelatin sponge in eight patients, while bleeding in one patient stopped spontaneously during angiography. Nine patients underwent prophylactic arterial catheterization before cesarean section or for abnormalities associated with risk of hemorrhage. Two subsequently underwent embolization before surgery, and embolization in two others was performed intraoperatively in response to serious bleeding. Bleeding in the other five was controlled by the usual surgical means. Arterial embolotherapy in these patients was an effective means of controlling postpartum hemorrhage. Prophylactic arterial catheterization has a role in patients with an increased risk for obstetric hemorrhage. PMID- 8511295 TI - Breast cancer recurrence after lumpectomy and radiation therapy for early-stage disease: prognostic significance of detection method. AB - The prognostic implications of detection mode in local recurrence after lumpectomy and radiation therapy were assessed. Seventy-two women treated with lumpectomy and irradiation for American Joint Committee on Cancer stages I and II invasive breast cancer developed recurrent cancer in the ipsilateral breast, had physical examination and mammography performed at the time of recurrence, and underwent salvage mastectomy. There was a statistically significant association between detection with mammography alone and lower T stage (P = .05), and there was a nonstatistically significant trend toward noninvasive histologic findings. No significant association was noted between detection method and site of recurrent current cancer in the breast, interval to recurrence, or patient age. There were nonstatistically significant trends toward improved relapse-free survival and overall survival for patients with recurrences detected solely with mammography. that postirradiation surveillance mammography is important for the early detection of recurrent cancer. While the trend did not reach statistical significance, detection with mammography alone had a clinically apparent impact on relapse-free and overall survival. PMID- 8511296 TI - Fine-needle aspiration cytology of nonpalpable breast lesions: US versus stereotaxic guidance. AB - The authors evaluated ultrasound (US)-guided fine-needle aspiration cytology (FNAC) in 270 patients with suspicious findings at mammography. FNAC with a 10 MHz transducer and real-time scanner was performed when a lesion seen mammographically was unequivocally depicted at US. The needle was inserted with variable obliquity to the scanning plane. Stereotaxically guided FNAC was performed when lesions were not visible at US. High suspicion at mammography and positive cytologic reports led to surgical biopsy. Of the 270 lesions, 120 (44.4%) were visible at US. Opacities were the most frequently visualized lesions. Inadequate samplings were most frequently reported for opacities with smooth margins. Differences in accuracy and inadequacy rate between the two modalities were not significant. Cancer was surgically confirmed in 86 of 110 cases. The other 160 lesions were considered benign, and mammographic follow-up in 120 has shown no change. Because FNAC with US guidance was faster and less expensive, it is recommended as the technique of choice in lesions detectable with US. PMID- 8511297 TI - Self-expandable prostheses in the tracheobronchial tree. AB - Under endoscopic and radiologic control, two types of self-expandable metal prostheses were implanted in tracheobronchial lesions to help reestablish airway caliber. Thirty-nine metal stent prostheses (6-20 mm in diameter) and 35 Gianturco stents (30 mm in diameter) were used in 55 adult patients with 62 lesions of the trachea (n = 33) or bronchi (n = 29). All lesions except one were endoscopically confirmed to be noninflammatory. Immediately after implantation, radiologic and endoscopic studies verified reestablishment of a satisfactory airway diameter in all patients. At a mean follow-up of 10.35 (range, 3-27) months, improvement in the respiratory status of 49 of the 55 patients (89%) was maintained and tolerance of the device was excellent. For the Wallstent endoprosthesis, the six complications observed at endoscopy were successfully treated. The Gianturco stent, however, led to a high rate of complications: 30% of cases had migration and/or rupture of the metallic mesh, potentially leading to obstruction or wall perforation; one case of respiratory distress was fatal. This procedure offers rapid epithelialization and incorporation of the device into the tracheobronchial wall. PMID- 8511298 TI - Malignant tracheobronchial obstructive lesions: treatment with Gianturco expandable metallic stents. AB - Gianturco expandable metallic stents were placed in 14 patients with 19 malignant lesions who had tracheobronchial stenosis and/or obstruction together with dyspnea. In all 14 patients, stenotic and/or obstructive changes disappeared immediately after the procedure, and the dyspnea improved. Lumina at the sites of tracheal lesions expanded from a mean of 3.9 mm in diameter before stent placement to a mean of 13.9 mm after stent placement. Lumina at the sites of bronchial lesions expanded from a mean of 2.1 mm to a mean of 10.3 mm. Lumina at the sites of lesions caused by extrinsic compression expanded to a mean of 89.7% of normal, while lumina at the sites of lesions caused by intraluminal tumor growth expanded to a mean of 63.2% of normal. There was improvement of at least one grade of the Hugh-Jones classification in 12 patients. Ten of the patients died; in two of these patients, restenosis developed. PMID- 8511299 TI - Parenchymal opacification in chronic infiltrative lung diseases: CT-pathologic correlation. AB - To correlate areas of parenchymal opacification on thin-section computed tomographic (CT) scans with histologic findings in patients with chronic infiltrative lung disease, the CT and histologic findings were evaluated in 29 patients with 11 such diseases. Open-lung biopsy was performed after CT. The area of predominant involvement was classified as air space, interstitium, or a mixture of both. A pathologic score of disease activity was assigned, and the extent of fibrosis was assessed whenever fibrosis was present. Parenchymal opacification on CT scans corresponded to abnormalities that affected mainly the air spaces in three patients (10%), the interstitium in 13 patients (45%), or both to a similar degree in 13 patients (45%). In 25 of 29 patients (86%), parenchymal opacification was associated with potentially treatable or reversible disease. Abnormalities considered irreversible were seen in three patients with end-stage fibrosis and one patient with talcosis. Parenchymal opacification on thin-section CT scans is a nonspecific finding in diseases that affect the air spaces, interstitium, or both but usually indicates potentially treatable or reversible disease. PMID- 8511300 TI - Hepatobiliary contrast material: a magic bullet for sensitivity and specificity? PMID- 8511301 TI - Measurement of scatter fractions in erect posteroanterior and lateral chest radiography. AB - Scatter fractions (SFs) measured in patients undergoing erect posteroanterior (PA) and lateral chest radiography with a 12:1 antiscatter grid are reported. Modifications to the posterior beam-stop (PBS) technique allowed measurement of scatter in these patients, without altering the diagnostic image and without additional radiation exposure. The SF measurements are reported by anatomic location on 42 clinical chest images. Average SF values ranged from 0.27 to 0.90 on lateral radiographs and from 0.27 to 0.68 on PA radiographs. Scatter measurements with the 12:1 grid were found to be greater than estimates from previous PA chest phantom experiments. To the authors' knowledge, they were the first to measure radiation scatter with the PBS technique in patients undergoing PA and lateral chest radiography with the antiscatter grid. PMID- 8511302 TI - Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. AB - To determine the influence of collagen orientation on the magnetic resonance (MR) imaging appearance of articular cartilage, spin-echo MR images of normal bovine patellar specimens were obtained with the specimens rotated in 5 degrees increments between +75 degrees and -130 degrees. Hyperintense superficial, hypointense middle, and intermediate-intensity deep laminae were observed. Results of polarized light microscopy of histologic specimens confirmed the three zones, and transmission electron microscopy showed different collagen arrangements in the zones. An anisotropic effect of rotation on signal intensity was evident, especially in the hypointense second lamina. Because of the preferential alignment of water molecules associated with collagen, angular rotation of the cartilage in the direction of minimum dipolar coupling (55 degrees to the magnetic field) caused the cartilage to have a homogeneous appearance. The MR imaging appearance of these layers is strongly influenced by an anisotropic arrangement of the collagen fibers and by the alignment of the specimen relative to the magnetic field. PMID- 8511303 TI - Intraarticular diffusion of Gd-DOTA after intravenous injection in the knee: MR imaging evaluation. AB - Intraarticular concentration of gadolinium tetraazacyclododecanetetraacetic acid (DOTA) after intravenous injection and the diagnostic contribution of the subsequent arthrographic effect were assessed for meniscal lesions in the knee. Kinetics were studied in three healthy volunteers. Passage of contrast material into the synovial fluid of the joint was evaluated in 53 knees by measuring the signal intensity on T1-weighted images before, immediately after, and 1 hour after injection. Synovial fluid enhancement was 1.46-fold greater than the unenhanced value after 10 minutes, plateaued after 30 minutes, and was 1.95-fold greater after 1 hour. In articular fluid samples from four patients 1 hour after intravenous injection, the average intraarticular concentration was 141 mumol +/- 47 (1 standard deviation) at atomic absorption spectrophotometry. Knee mobilization improved the passage of contrast material into the synovial fluid by approximately 120% at 10 minutes and 25% at 1 hour. In eight of 39 tears, unenhanced standard sequences were equivocal. In seven of these uncertain cases, delayed contrast-enhanced images permitted adequate interpretation. Intraarticular concentration of Gd-DOTA produces a sufficient arthrographic effect for meniscus evaluation. PMID- 8511304 TI - Radiation-induced insufficiency fractures of the sacrum: evaluation with MR imaging. AB - In patients with malignant pelvic tumors, radiation-induced insufficiency fractures of the sacrum may be mistaken for metastasis. Magnetic resonance (MR) imaging was performed in 18 patients with this condition, and the findings were studied retrospectively. The diagnosis was confirmed with at least one additional imaging modality in 16 patients, whereas the other two patients underwent clinical follow-up at 13 and 20 months without evidence of metastasis. In 17 patients, the lesions were consistent with edema and had diffuse low signal intensity on T1-weighted images and diffuse high signal intensity on short inversion-time inversion-recovery images, thereby simulating metastasis. In one patient, bilateral sacral wing fractures were demonstrated directly as fairly well-defined linear zones. The alae sacri were involved in all patients; 16 patients had bilateral lesions. Awareness of this clinical entity and of the high sensitivity of MR imaging for demonstrating edema caused by the fracture should prevent confusion with metastatic disease and inappropriate treatment. PMID- 8511305 TI - Periosteal ganglia: CT and MR imaging features. AB - The imaging features of four cases of periosteal ganglia were studied. Three lesions were located over the proximal shaft of the tibia, in proximity to the pes anserinus. The fourth lesion involved the distal shaft of the ulna. Three lesions had different degrees of external cortical erosion, scalloping, and thick spicules of periosteal bone on plain radiographs. The bone adjacent to the fourth lesion was not involved. Computed tomography (CT) showed these lesions to be sharply defined soft-tissue masses abutting the periosteum. All of the lesions had the same attenuation as fluid. Magnetic resonance (MR) imaging revealed the ganglia to be sharply defined masses that were isointense compared with neighboring muscles on T1-weighted images. There was markedly increased signal intensity compared with that of fat on T2-weighted images. The signal intensity on both types of images was homogeneous. The MR imaging features were consistent with the fluid nature of the lesions. Under the appropriate clinical circumstances, the MR imaging and CT features of periosteal ganglia are diagnostic. PMID- 8511306 TI - Bull's-eyes and halos: useful MR discriminators of osseous metastases. AB - To evaluate the presence of (a) a focus of high signal intensity in the center of an osseous lesion (bull's-eye) as a negative discriminator for metastasis and (b) a rim of high signal intensity around an osseous lesion (halo) as a positive discriminator, a retrospective study was performed in 47 patients with osseous lesions suspect for metastatic disease who underwent magnetic resonance (MR) imaging of the pelvis. The findings in 17 patients with proved osseous metastasis were compared with those in 30 patients not believed to have metastatic disease; T1- and T2-weighted MR images were evaluated. The bull's-eye sign was found to be a specific indicator of normal hematopoietic marrow (sensitivity, 95%; specificity, 99.5%). The halo sign and diffuse signal hyperintensity were a strong indicator of metastatic disease (sensitivity, 75%; specificity, 99.5%). These results suggest that use of the bull's-eye sign as a discriminator of benign disease and use of the halo sign as a discriminator of metastasis help characterize suspect areas of marrow lesions. PMID- 8511307 TI - Cervical spine: comparison of 45 degrees and 55 degrees anteroposterior oblique radiographic projections. AB - The orientation of the intervertebral foramina (IVF) at six cervical levels on transaxial images in 65 magnetic resonance (MR) studies was determined to explain variations in size and shape evident on the 45 degrees standard radiographic oblique view. Analysis of MR imaging data showed that substantial variations in the orientation of the cervical IVFs occurred throughout the cervical spine and that a 55 degrees anteroposterior (AP) oblique view with standard radiography probably would lead to better visualization of the lower cervical IVFs. These results were confirmed with a radiographic and anatomic study of two cadaveric specimens. In a prospective clinical study of 23 patients, 45 degrees and 55 degrees AP oblique views were compared by measuring the maximal transverse diameter of all the cervical IVFs. IVF size was substantially increased on the 55 degrees AP oblique projection at all lower cervical levels. The 55 degrees AP oblique view of the cervical spine is optimal for evaluating the lower cervical foramina and can be a routine alternative to the 45 degrees oblique view in the analysis of all cervical foramina. PMID- 8511308 TI - Prophylactic radiation therapy for prevention of heterotopic ossification after hip arthroplasty: results in 141 high-risk hips. AB - In a 4 1/2-year, prospectively randomized study, 137 patients with 141 hips at high risk for heterotopic ossification (HO) received prophylactic radiation therapy (RT). Patients were randomly assigned to a low-dose regimen of five fractions of 2 Gy each (n = 73) or a high-dose regimen of either 10 fractions of 2 Gy each (n = 7) or five fractions of 3.5 Gy each (n = 61). Treatment failure was assessed by comparing immediately postoperative radiographs with radiographs obtained at least 6 months after hip surgery (Brooker grading score). Positive responses (ie, effective prophylaxis of HO) were seen in 129 (91.5%) hips. Treatment failures were observed in 12 (8.5%). Use of a nonsteroidal antiinflammatory drug (NSAID) lowered the failure rate in both RT groups. High RT dose with a short duration (< or = 9 days) and use of an NSAID was significantly (P = .009) correlated with treatment success. RT delivered within a few days after hip surgery is effective in preventing HO, even in high-risk patients, and provides an excellent alternative for patients with contraindications to long term medication with either NSAIDs or corticosteroids. PMID- 8511309 TI - Postoperative hip irradiation in prevention of heterotopic ossification: causes of treatment failure. AB - Over 4 years, 33 patients (mean age, 52 years) underwent hip surgery followed by single-fraction 700-cGy radiation therapy (RT). Records, port films, and plain radiographs were reviewed to assign Brooker classification levels for severity of heterotopic ossification (HO) and assess the amount of new HO developing after surgery. Nineteen patients (58%) developed radiographic evidence of new HO after surgery. All five patients with three or more risk factors and none of 12 with postoperative Brooker level 0 (no radiographic HO) developed new HO. Ten of 16 treated on postoperative day 1, six of 10 on postoperative day 2, none of three on day 3, two of three on day 4, and one of one on day 5 developed new HO. New HO developed outside the irradiated volume in 11 patients. Surgeons should remove all heterotopic bone whenever possible; RT should be administered within 3 days after surgery; portals should cover all potentially involved soft tissue; and future studies should evaluate larger single fractions (900-1,000 cGy) for prevention of HO in patients with three or more risk factors and/or radiographic evidence of residual HO. PMID- 8511310 TI - Self-referral: the need for a comprehensive regulatory approach. PMID- 8511311 TI - Scatter in computed radiography. AB - The effects of scatter radiation on images obtained with storage phosphor computed radiography (CR) were evaluated. The scatter degradation factor was extended to account separately for forward scatter and backscatter. Values for the ratios of forward scatter to primary radiation (sf/p) and backscatter to primary radiation (sb/p) were measured for various x-ray tube potentials, phantom thicknesses, and field sizes for CR imaging plates (IPs). Similar measurements were made for a common screen-film system. The sb/p values for the IPs were 0.05 3.80. Standard CR cassettes do not have lead foil behind the IP to control backscatter; the results of this study indicate that such control is needed. The sf/p values were 40%-70% higher in IPs (50%-120% higher when backscatter was included) than those in the conventional screen-film system. This difference is attributed to the differences in the K-absorption edges of barium and gadolinium and the fact that scatter has lower effective energy than the primary beam as they exit the patient. PMID- 8511312 TI - Mahmood F. Mafee, MD, 1993-1994 distinguished scientist, Department of Radiologic Pathology, Armed Forces Institute of Pathology. PMID- 8511313 TI - Multisection proton MR spectroscopic imaging of the brain. AB - The authors developed a hydrogen-1 proton magnetic resonance (MR) imaging method in which metabolic information is acquired by obtaining multiple sections through the brain. A spin-echo sequence is used for section selection, an octangular outer volume saturation pulse for lipid suppression, and a chemical-shift selective saturation pulse for water suppression. High-quality maps of choline, creatine, and N-acetylaspartate were obtained in six studies performed in four volunteers. Water and lipid signal from the skull area was well suppressed by the pulse sequence used. PMID- 8511314 TI - Need for caution during MR imaging of patients with aneurysm clips. PMID- 8511315 TI - Our name. PMID- 8511316 TI - Confluent hepatic fibrosis in advanced cirrhosis: appearance at CT. AB - To determine the computed tomographic (CT) characteristics of confluent fibrosis complicating liver cirrhosis, CT scans of 420 cirrhotic patients without hepatic malignancy who underwent hepatic transplantation were correlated with freshly resected whole liver specimens. In 59 patients, CT demonstrated 70 focal abnormalities corresponding to confluent fibrosis. The lesions were characterized by shape and location: 49 wedge-shaped lesions radiated from the porta hepatis, eight peripheral bandlike lesions were remote from the porta hepatis, and 13 lesions were seen as total lobar or segmental fibrosis. Associated volume loss was seen in 62 of the 70 lesions as retraction of the overlying hepatic capsule or total shrinkage of the segmental or lobar involvement. At plain CT, all 70 lesions were areas of lower attenuation than adjacent liver. At contrast material enhanced CT, 51 of 64 lesions were iso-attenuating or minimally hypo-attenuating. The authors conclude that confluent fibrosis has a characteristic appearance at CT. Recognition of its characteristics may help radiologists differentiate confluent fibrosis from hepatic neoplasms in cirrhotic patients. PMID- 8511317 TI - Chronic hepatitis and cirrhosis: evaluation by means of MR imaging with histologic correlation. AB - To characterize the relationship between findings on magnetic resonance (MR) images and histologic changes in chronic liver disease, a prospective study was performed in 100 patients with chronic hepatitis and cirrhosis and 28 healthy subjects. Biopsy specimens, obtained in all patients before MR imaging, were evaluated with the histologic activity (HA) index; MR images were obtained with short inversion time inversion-recovery (STIR) and spin-echo sequences. On STIR images, normal livers were iso-intense to fat. Significant differences (P < .001) existed between signal intensity of normal livers and that of diseased livers, which were brighter than normal livers on STIR images. The ratio of signal intensity of liver to that of fat on STIR images was associated with an HA index grouped by severity (P < .05): Patients with higher HA scores had a brighter liver. Signal intensity ratios on MR images were statistically significantly associated with periportal and lobular necrosis and portal inflammation. The signal intensity of liver on STIR images is associated with the degree of histologic severity in patients with chronic liver disease. PMID- 8511318 TI - Obstruction of the small intestine: accuracy and role of CT in diagnosis. AB - The reliability of abdominal computed tomography (CT) in the assessment of varying degrees of small bowel obstruction (SBO) was evaluated by using results at enteroclysis and clinical outcome as standards of reference. A blinded retrospective analysis was performed of the studies of 55 patients who underwent both CT and enteroclysis in the course of assessment for suspected SBO. Nine patients had no obstruction, 40 patients had obstruction due to adhesions, and six patients had tumor-related obstruction. CT results were used to identify correctly 63% (29 of 46) of those who had SBO and 78% (seven of nine) of the patients who did not. The overall accuracy of the CT interpretations to help establish diagnosis was 65% (36 of 55). When obstructions were classified into low- and high-grade partial obstruction, CT results could be used to identify correctly 81% (17 of 21) of high-grade SBOs and 48% (12 of 25) of low-grade SBOs. The procedure yielded two false-positive and 13 false-negative results for patients with low-grade obstruction, revealed masses in all six cases with tumor related obstruction, and helped predict the correct cause in all true-positive cases. PMID- 8511319 TI - Intestinal Behcet disease: serial changes at radiography. AB - To clarify the characteristic radiographic findings and serial radiographic changes in nonsurgical cases of intestinal Behcet disease (BD), seven patients were followed up for an average of 4 1/2 years (range, 8 months to 11 years 4 months). They underwent repeated examination with barium meal studies and double contrast barium enema meal studies and double-contrast barium enema radiography. Initial radiography revealed one to three deep ulcers in the terminal ileum or ileocecal region in five patients. The ulcers healed while patients were treated with medical therapy but recurred during the follow-up period. In four of these five patients, follow-up radiography demonstrated various changes within each case: At each examination, an enlarged ulcer or a newly developed ulcer was often found in conjunction with a healed ulcer. In the other two patients, multiple shallow ulcers or innumerable aphthoid ulcers were seen throughout the entire colon, and these ulcers showed a good response to medical treatment. These results indicate that serial radiographic changes in patients with intestinal BD may mimic those in patients with Crohn disease, with findings in the terminal ileum and colon that wax and wane with medical treatment. PMID- 8511320 TI - Appendicitis caused by carcinoid tumor. AB - A previously healthy man had a carcinoid tumor that caused obstruction and dilatation of the appendiceal lumen, with subsequent inflammation of the appendix. He had acute pain in the lower right abdomen, loss of appetite, constipation, pyrexia, and an increased erythrocyte sedimentation rate without leukocytosis. Although his clinical signs and symptoms subsided, the persistent pathologic finding of a large dilated appendix at examination with ultrasound warranted surgery, which, with microscopy, established the correct diagnosis. PMID- 8511321 TI - Portal vein embolization: utility for inducing left hepatic lobe hypertrophy before surgery. AB - Right portal vein embolization (PVE) was performed in patients in need of wide hepatectomy to induce preoperative hypertrophy of the future remnant liver (FRL), which would have been insufficient for safe resection. PVE was achieved with cyanoacrylate or gelatin sponges by using a percutaneous subxiphoid approach in 10 patients with tumors in noncirrhotic liver. Surgery was performed in nine patients 17-48 days (mean, 34 days) after PVE. Computed tomographic liver volumetric studies were performed before embolization and before surgery. Clinical and biologic tolerance of PVE was excellent except in one case. Histopathologic studies showed occlusion of portal veins with minimal parenchymal ischemia in eight of nine patients. The FRL volume increased by 64%, which represented 31% of the preresection volume of the liver. Better hypertrophy was seen after cyanoacrylate embolization. The authors conclude that PVE is safe and well tolerated and induces marked hypertrophy of the unembolized parenchyma in noncirrhotic patients. This hypertrophy allows hepatectomy to be performed under safe conditions when the FRL volume is initially insufficient. PMID- 8511322 TI - Hepatic arterial injury after transjugular intrahepatic portosystemic shunt placement: report of two cases. AB - Transjugular intrahepatic portosystemic shunts (TIPS) were placed in two patients for treatment of variceal hemorrhage and refractory ascites. In both patients, branches of the right hepatic artery were inadvertently punctured during portal vein localization. In one case, right hepatic artery occlusion resulted in irreversible liver failure. In the other case, intraperitoneal bleeding resulted from the arterial injury. Embolization could not be performed due to celiac axis occlusion. Four days after surgical repair, the patient died of multiorgan failure. Hepatic arterial injuries are a serious complication of TIPS creation. Aggressive efforts to recanalize occlusions and superselective embolization of extravasation are recommended. PMID- 8511323 TI - Self-expandable spindle for transcatheter vascular occlusion: in vivo experiments. Work in progress. AB - A mechanical vascular occluder was studied in eight pigs to test its efficacy in arteries of different diameters, stability over time, and safety in placement. The main component is a self-expandable spindle made of tubular stainless steel mesh. Simple steel spindles, double spindles, and Dacron-core spindles were placed in the common carotid artery, main renal artery, renal artery branches, and infrarenal aorta. Follow-up arteriograms were obtained immediately, 30-60 minutes, and (except for aortic spindles) 7 days after deployment. The left common carotid artery was occluded in all pigs, regardless of spindle type. In the main renal artery and its branches, simple steel spindles did not achieve complete occlusion. Double and Dacron-core spindles produced immediate occlusion without recanalization on the 1-week follow-up arteriogram, except for one spindle with an incomplete Dacron core and two spindles that did not completely fill the arterial lumen. Two Dacron-core spindles achieved immediate complete occlusion of the infrarenal aorta. No migration was seen with any spindle. PMID- 8511324 TI - [Asceticism and ecstasy in Freud]. AB - Contrasting concepts like "denial" and "fulfillment" are indicative of conflicting pulls in Freudian theory that can also be described in terms of the tension between "asceticism" and "ecstasy". The author divides Freud's thinking into three distinct phases--demonological speculation, labyrinthine speculation, cosmogonical speculation--and demonstrates that in each of these phases the relative emphasis on the ascetic and the ecstatic differs. Further, Due points out that on the formal level Freud's theories are affected by those phenomena which he defines as being ascetic or ecstatic in nature. In terms of the history of ideas, the author sets the opposition between asceticism and ecstasy against the broader horizon of the opposition between Enlightenment and Romanticism. PMID- 8511325 TI - [Rousseau on the couch. "La nouvelle Heloise as a key to his childhood trauma]. AB - Whereas many interpreters and biographers of Rousseau tend to present their subject as a pathological figure, Niemeyer will have no truck with such ascriptions. His reading of Rousseau's epistolary novel Julie ou la Nouvelle Heloise (1761) draws upon the autobiographical Confessions and reveals that Rousseau uses this novel as a species of self-therapy. In the novel the constellations in which certain scenes recur invite their interpretation as complementary scenes to Rousseau's traumatic "Urszene"--the death of his mother when giving birth to him. In Niemeyer's view, the way in which Rousseau turns his re-working of his childhood trauma to literary account qualifies him as a predecessor of psychoanalysis. PMID- 8511326 TI - [The future of a nation. Political and psychoanalytic reflections on German re unification]. AB - Taking a lead from Alexander and Margarete Mitscherlich's psychogram of post-war German society in The Inability to Mourn and Heinz Kohut's remarks on a theory of narcissism, the authors interpret the over-hasty reunification process and the liquidation of the GDR as an attempt to remedy the precarious nature of the collective narcissistic equilibrium. As in the post-war period, when concern with the immediate past was stifled by "reconstruction" and the "economic miracle", so the advent of "deutschmark nationalism" after 1989/90 was marked by the central role played by money. In the emotional cathexis centering around money the authors identify a collective tendency to restore a lost self-object and revive an archaic megalo-self that was thought to have been abandoned for good with the downfall of Hitler. PMID- 8511327 TI - Becoming an independent midwife. PMID- 8511328 TI - Help stop the violence. 'Handle with care'. PMID- 8511329 TI - Sleep apnoea--what you should know. PMID- 8511330 TI - Defamation in references, reports and memos prepared at your health service. PMID- 8511331 TI - Neurohypophysial peptide systems: processing machinery, hydroosmotic regulation, adaptation and evolution. PMID- 8511332 TI - Inputs from the nucleus tractus solitarii to the magnocellular neurosecretory system. PMID- 8511333 TI - Vasopressin and behavior: from memory to olfaction. PMID- 8511334 TI - The role of neurohypophyseal peptides in the central mediation of complex social processes--evidence from comparative studies. PMID- 8511335 TI - Neurohypophyseal peptides and psychiatric diseases. AB - The study of neurohypophyseal function in various neuropsychiatric diseases is interesting because: (1) The main neurohypophyseal peptides vasopressin (AVP) and oxytocin (OT) share by themselves modulatory influence on behavior. (2) Hypothalamo-posterior pituitary axis is directly influenced by modifications of central neurotransmitter metabolism involved in behavior control. PMID- 8511336 TI - Role of central oxytocinergic pathways in the expression of penile erection. PMID- 8511337 TI - Neurohypophysial peptides in the human hypothalamus in relation to development, sexual differentiation, aging and disease. AB - The two neuronal systems that contain neurohypophysial peptides in the hypothalamus i.e. (i) the supraoptic and paraventricular nucleus and (ii) the suprachiasmatic nucleus, show quite different patterns of changes in the human in relation to development, aging and disease. PMID- 8511338 TI - Central oxytocin inhibition of food and salt ingestion: a mechanism for intake regulation of solute homeostasis. PMID- 8511339 TI - Structure and folding properties of neurophysin and its peptide complexes: biological implications. PMID- 8511340 TI - Differential regulation of neurohypophysial peptides in the paraventricular nucleus. PMID- 8511342 TI - The role of oxytocin and vasopressin in the initiation of preterm and term labour as well as primary dysmenorrhoea. PMID- 8511341 TI - Putative factors implicated in the structural plasticity of the hypothalamo neurohypophysial system. PMID- 8511344 TI - Is there a paracellular water pathway in inner medullary collecting ducts (IMCD) from dehydrated rats? PMID- 8511343 TI - The influence of gonadal steroids on the release and actions of neurohypophysial hormones. PMID- 8511345 TI - Vasopressin receptors and effects during fetal development. PMID- 8511347 TI - Vasopressin homeostasis: coordination of synthesis, storage and release. PMID- 8511346 TI - The role of volume hormones in the excretion of water loads. PMID- 8511348 TI - Vasopressin regulation of cell growth in Swiss 3T3 cells. PMID- 8511349 TI - Oxytocin modulation of gonadotrophin release. PMID- 8511351 TI - Hypothalamic slice-explant cultures as models for the long-term study of gene expression and cellular activity. PMID- 8511350 TI - Synthesis of oxytocin in amnion, chorion and decidua: a potential paracrine role for oxytocin in the onset of human parturition. PMID- 8511352 TI - Oxytocin, a male intragonadal hormone. AB - It is now well recognised that oxytocin is not confined to the hypothalamo neurohypophysial system but present elsewhere in the body. However, the significance of the peptide in these peripheral sites is still unclear. This paper considers the evidence for oxytocin to be a male gonadal hormone and focusses on three of the criteria which need to be fulfilled for it to earn this title: oxytocin must be produced within the gonads; have a physiological action and be regulated by factors which alter gonadal function. PMID- 8511353 TI - Oxytocin gene expression and action in bovine preovulatory follicles. AB - We have studied oxytocin (OT) gene expression, secretion, and action in bovine preovulatory follicles during the follicular phase of the estrous cycle. OT is secreted in vitro by follicular granulosa cells, but not by theca cells. Both OT content of granulosa cells and their ability to secrete OT in culture increased dramatically when follicles were obtained after the gonadotropin surge (LH surge) that triggers ovulation. These changes were correlated with increased levels of messenger RNA (mRNA) for OT in granulosa cells obtained after vs. before the LH surge. When granulosa cells were obtained before the surge, both OT secretion and OT mRNA levels increased with time in culture, and the increases were greatly enhanced in the presence of LH. Estradiol, at concentrations found in follicular fluid of preovulatory follicles before the LH surge, inhibited OT secretion in vitro, whereas concentrations found in follicular fluid after the LH surge were not inhibitory. Progesterone, at physiological concentrations, stimulated OT secretion in vitro. We have shown previously that OT increases progesterone secretion by granulosa cells obtained before the LH surge. Taken together these results show that, during the follicular phase in cattle, OT secretion and gene expression are coordinately regulated and suggest that they are regulated by both gonadotropins and intrafollicular steroids. Increases in OT after the LH surge may play a role in the follicular/luteal phase shift in steroidogenesis from estradiol/androgen to progesterone. PMID- 8511354 TI - The regulation of neurohypophyseal peptide gene expression in gonadal tissues. PMID- 8511355 TI - Oxytocin- and vasopressin-like immunoreactivity in the rat thymus: characterization and possible involvement in the immune response. PMID- 8511356 TI - Thymic neurohypophysial-related peptides and T cell selection. PMID- 8511357 TI - Design of cyclic and linear peptide antagonists of vasopressin and oxytocin: current status and future directions. PMID- 8511358 TI - Development and pharmacological assessment of novel peptide and nonpeptide oxytocin antagonists. PMID- 8511359 TI - Terlipressin (glypressin) in the treatment of bleeding esophageal varices. State of the art. PMID- 8511360 TI - Central diabetes insipidus: oral treatment with dDAVP. PMID- 8511361 TI - Enuresis nocturna: long term use and safety aspects of minrin (desmopressin) spray. PMID- 8511363 TI - Desmopressin and hemostasis. PMID- 8511362 TI - Transactivation of the rat oxytocin and vasopressin promoters by nuclear hormone receptors. PMID- 8511365 TI - Uterine oxytocin gene expression: a novel framework for oxytocin action. PMID- 8511364 TI - Regulation of the extent of polyadenylation of vasopressin and growth hormone mRNAs in response to physiological stimuli. PMID- 8511366 TI - Vasopressin gene expression in explant and dispersed hypothalamic cultures. PMID- 8511367 TI - Molecular cloning and expression of rat V1a and V2 arginine vasopressin receptors. AB - Vasopressin, one of the first characterized neuropeptides, has a wide spectrum of biological action, acting on distinct tissues. Indeed, it is involved in water retention, glucose metabolism, blood pressure and its implication in the CNS has also been described. This diversity of effects on mammalian tissues is mediated by distinct G protein-coupled receptors, acting via distinct second messenger pathways. This receptor family has been subtyped by pharmacological studies, as V1a receptor whose action is mediated by intracellular calcium mobilization, and V2 receptor which is linked to adenylyl cyclase. Since so many essential functions were ensured by vasopressin, molecular characterization of its receptors became soon a great challenge. This prompted us to isolate the cDNA of AVP V1a receptor as the first member of this family, by expression cloning. Intracellular calcium mobilization was therefore assayed after rat liver mRNA injection into Xenopus oocytes. A single clone, encoding a functional AVP receptor corresponding to the V1a subtype was finally characterized as a G protein-coupled receptor. Furthermore, we used homology cloning strategy in order to clone the AVP V2 subtype from a rat kidney cDNA library. A putative receptor clone was finally characterized as the rat V2 receptor cDNA by binding and cAMP increase experiments, on transfected cells. PMID- 8511368 TI - Expression cloning of the human V2 vasopressin receptor. PMID- 8511369 TI - The vasopressin type 2 receptor gene. Chromosomal localization and its role in nephrogenic diabetes insipidus. PMID- 8511370 TI - Cytoplasmic and nuclear signaling pathways of V1-vascular vasopressin receptors. AB - We studied the cytoplasmic and nuclear signaling pathways of V1-vascular AVP receptors of human platelets, primary cultures of renal glomerular mesangial cells, and established cultures of the A7r5 aortic smooth muscle cell line. The immediate transmembrane signals are triggered by the formation of ligand-receptor complexes as illustrated by binding experiments with [3H]AVP (Kd = 2.50 nM), d(CH2)5Tyr(Me)AVP (Kd = 0.62 nM), the linear V1 antagonist phenylacetyl-D-Tyr(Et) Phe-Val-Asn-Lys-Pro-[125I]Tyr-NH2 (Kd = 1.42 nM) or by fluorescence experiments with linear antagonists like phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 coupled to biotin and made fluorescent by labeling with tetramethylrhodamine avidin. We used several approaches (radioreceptor binding, radioactive labeling, autoradiographic, enzymatic, photoaffinity labeling, and immunoblotting procedures) to identify the guanine nucleotide regulatory protein coupled to V1 vascular vasopressin receptors. AVP-stimulated GTPase activity of human platelet membranes was blocked by pretreatment with antibodies specific for the C-terminal of the newly described Gq alpha protein. In the presence of MgCl2, AVP increased labeling by the photoreactive GTP analog [alpha-32P]azidoanilido GTP of a platelet membrane protein of apparent molecular mass of 42 kDa. AVP effect was reversed by the specific V1-vascular antagonist d(CH2)5Tyr(Me)AVP and labeling was completely abolished by GTP gamma s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511371 TI - Role of AVP in the regulation of vascular tonus and blood pressure in patients with chronic renal failure. AB - This study was undertaken to estimate the role of AVP in the regulation of vascular tonus and blood pressure, at first, during hemodialysis hypotension and, secondly, in hypertensive patients with chronic renal failure (CRF). Study 1: among 12 patients with hemodialysis (HD) hypotension showing similar metabolic and endocrine changes except plasma AVP during HD, 6 who showed an increase in plasma AVP after HD were hemodynamically examined during HD. Gradual decreases in mean BP and cardiac index, and increases in systemic vascular resistance (SVR) and plasma AVP, with a slight time-delay, were observed and thereafter BP inversely showed a slight increase at the end of HD, whereas no significant change in HR was found throughout HD. However, the % change in SVR had a positive correlation with % change in plasma AVP levels (P < 0.01, r = 0.559), but not with that in plasma renin activity or plasma norepinephrine levels. Study 2: oral administration of 100 mg of AVP.V1-receptor antagonist, OPC21268, which completely inhibited the vasoconstriction induced by the exogenously administered AVP, did not show any changes in BP and HR of seven hypertensive CRF patients. However, OPC21268 results in a marked decrease in BP of one hypertensive CRF patient with congestive heart failure (CHF) and nephrotic syndrome. Therefore, in some patients with HD hypotension showing impaired SNS and RAS, AVP may play an important role in the maintenance of BP during HD, predominantly via its peripheral vasoconstrictive action. On the other hand, AVP might not aggressively participate in hypertension of CRF patients, even with relatively high levels of plasma AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511372 TI - Oxytocin-endothelin interactions in the uterus. PMID- 8511373 TI - [The current status of the coronary stent]. PMID- 8511374 TI - [Tetanus in the Murcia region: the clinico-epidemiological characteristics of 150 cases]. AB - 150 tetanus cases registered on the region of Murcia have been retrospectively analyzed, they have been collected from the patients admitted at a Intensive Care Unit during a period of 18 years; the clinical together with the epidemiological features, as well as their variations, have been studied through out the years. The impact of a vaccination program in adults which was performed in our region during 1981 has been also evaluated in relationship with the incidence of disease and the economical cost of it. Incidence remained homogeneous until 1982, from that date on a sudden decrease on the number of cases was observed, related with the vaccination program [Period previous to the vaccination program: mean 10 cases/year, versus 5 cases/year since it was started (p < 0.001)]. Regarding the epidemiological characteristics, it is remarkable the shift of the disease toward a more advanced age of onset together with a predominance on females beginning in 1978, but without reaching statically significance. More frequent route of infection is nowadays the intramuscular suppurative injection. Besides this fact the severity of the cases have been increasing (from 59% to 71%, p < 0.005), which has determined that the global mortality of the disease remains almost the same (38%). Mortality has no relationship with age, but is related with being a female (p < 0.05), with intramuscular injection as route of infection (p < 0.025), with the clinical stage (p < 0.001) and with a short incubation period (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511375 TI - [The long QT syndrome: epilepsy as the form of presentation]. AB - Prolongation of the QT interval, either on a congenital or an acquired basis, is associated with an increased likelihood of malignant ventricular arrhythmias with a high rate of morbimortality. Symptoms are variables, and patients may develop seizures, syncope and sudden death. Herein we report a young woman 17 years old with long QT syndrome, seizures and recurrent attacks of syncope; her initial diagnosis was primary epilepsy. An electrocardiogram performed 3 years after the initials symptoms was able to make the diagnosis long QT syndrome. The specific treatment controlled the malignant ventricular arrhythmias and the symptomatic status of this patient. PMID- 8511376 TI - [The association of pleural empyema and perinephritic infection: apropos 4 cases]. AB - Empyema of renal origin is very rare (3% in our series). We discuss 4 cases of empyemas associated to perirenal infection. Two of them were diabetic and all of them have renal lithiasis. They made their debut through pleural effusions, isolating Escherichia coli in all of them. Treatment was antibiotics and drainage in both foci, three of them evolved to healing and one of them died being the abdominal foci without drainage. This association must be suspected when no clear etiology of the empyema is present in patients with history of renal lithiasis and diabetes. PMID- 8511377 TI - [Melanocytic schwannoma: a rare tumor originating in the neural crest. Apropos a case associated with Horner's syndrome]. AB - Schwann cells tumors, producing melanin, are extremely rare and pose difficult problems for its differential diagnoses from melanomas, which are tumors with different prognostic and treatment. In this paper a new case is described, which debuts as Claude-Bernard-Horner syndrome being diagnosed with the help of Immunohistochemistry and Electronic Microscopy. PMID- 8511378 TI - [The approach to the quality of life in the chronic respiratory patient]. AB - Due to the fact that the treatment in chronic respiratory patients is almost completely palliative, it is important to find some kind of scale which can yield precise information on the limitations which the subject has to face on his/her day-to-day life. Respiratory function tests and dyspnea scales are not appropriately enough systems for such purpose, therefore during the last few years several CV tests have been applied, general or specific, standardized or not. The method which currently seems more useful is CRQ, even tough SGRQ seems to be the more promising, due to the fact that it has been fully standardized and allows interindividual as well as and in interpopulation comparisons. PMID- 8511379 TI - [Psychosocial factors and the compliance with drug prescriptions in depressed patients: a clinical contribution]. AB - The present paper summarizes the results of a clinical investigation developed on 35 depressed outpatients. Several clinical and psychosocial variables were isolated with the aim of establishing which of them could be related with a premature treatment withdrawal. The results are discussed and the responsibility of psychosocial factors in treatment compliance is stressed. Personality traits, family support, and negative life events seem to be the most significant factors associated to non-adherence. In the author's opinion, these factors could be related to the treatment compliance not only in depressive disorders but also in many other medical and psychiatric diseases. PMID- 8511380 TI - [High doses of chemotherapy in the treatment of breast cancer: the current prospects]. PMID- 8511381 TI - [Clozapine and monocytosis]. PMID- 8511382 TI - [Pneumothorax secondary to the placing of a nasogastric feeding tube: 2 new cases]. PMID- 8511383 TI - [Isolated laryngeal candidiasis in a patient with disseminated tuberculosis]. PMID- 8511384 TI - [Arrhythmias and cocaine]. PMID- 8511385 TI - [Sinusitis, bronchiectasis and azoospermia: apropos a case]. PMID- 8511386 TI - [Psychiatric disorders in diabetes mellitus. Their influence on metabolic control]. PMID- 8511387 TI - [Empyema due to the aspiration of a foreign body]. PMID- 8511388 TI - [Hyperthyroidism as the trigger of ketoacidotic decompensation in insulin dependent diabetes mellitus]. PMID- 8511389 TI - [Peripheral circulatory insufficiency with severe arterial thrombosis preceding by 3 years a diagnosis of essential thrombocythemia]. PMID- 8511390 TI - [Visceral leishmaniasis: its epidemiology, clinical picture and therapy]. PMID- 8511391 TI - [The new education of the physician in the Italian university. Postgraduate training]. PMID- 8511392 TI - [Hodgkin's lymphoma and secondary leukemias]. AB - The increase of survival in patients with Hodgkin's disease (HD) has made appear the problem of secondary neoplasms, included acute leukemias. The authors evaluate the incidence of acute leukemias in 205 HD with a follow-up more than 12 months (mean 92 months). With regard to these latter, 18 (8.7%) were treated with radiotherapy alone, 69 (33.6%) with chemotherapy alone and 118 (57.5%) with a combination of radiotherapy and chemotherapy. Chemotherapy consisted of 2-12 courses of MOPP alone or in combination with ABVD. The relative risk of acute leukemias is 96.7 (CI 95%: 44.2-183.6): nine cases against an expectancy of 0.093. The risk changes during five-years periods, but not significantly, and it not declines after ten years from the diagnosis. Only the alkylating chemotherapy seems to be important to favour the onset of acute leukemias. Among the patients who received a number of courses of MOPP less or equal than 6 (177), seven developed an acute leukemia (relative risk 85.3; CI 95%: 34.3-175.9); among those who received more than 6 (9), two developed an acute leukemia (relative risk 333.3; CI 95%: 40.3-1204.1). Neither the addition of radiotherapy nor the stage nor the splenectomy nor the histotype favour the onset of acute leukemia. PMID- 8511393 TI - [Leiomyosarcoma of the renal hilus]. PMID- 8511394 TI - [Immunomodulating therapy in high-risk urologic surgery. The results with thymostimulin]. PMID- 8511395 TI - [The adjuvant treatment of operable breast carcinoma. The current status and outlook]. AB - Breast cancer represents one of the most frequent neoplasm: every year, in Italy, 25,000 new cases are diagnosed with more than 9,000 deaths. In Italy--and also in other countries--has been shown a broad variability in the use of diagnostic or therapeutic procedures caused by different hospitals' characteristics, patients' conditions and physicians' opinions. Among the different therapeutic options, post-surgical therapy, that extends the disease-free interval and survival, fills an important position in the cure of breast cancer in relation to the overview published on Lancet the 4th and the 11th January 1992. According to this overview, patients who had surgery for breast cancer benefitted by an adjuvant therapy--hormonal or cytotoxic--with a reduction of mortality between 15 and 20%. That means, in Italy, a reduction of one thousand deaths per year for this neoplasm. Particularly the effectiveness of hormonal treatment in postmenopausal patients (not only in the oestrogen receptor (ER) positive but in the ER poor too), of ovarian ablation and chemotherapy in premenopausal patients was confirmed. In node negative patients the present overview recommends the adjuvant treatment for the risk reduction in recurrence and mortality. Nevertheless important research implications persist about treatment and a better definition of high risk patients; therefore more patient should be included in the randomized clinical trial. PMID- 8511396 TI - [Hairy-cell leukemia]. AB - This is a review of current opinions on all aspects of diagnosis and treatment of hairy-cell leukemia. First, the authors report a concise but complete description of clinical and hematological characteristics of the disease with particular attention to peripheral blood and bone marrow morphological, cytochemical and cytogenetic features. Still concerning the diagnostic phase, the authors report a brief description of splenic, hepatic and lymph nodal histological pictures and some informations about immunophenotypic diagnosis with monoclonal antibodies. A space is then given to differential diagnosis and prognostic factors which have remarkably changed over the years. The second part of this review concerns current treatments for hairy-cell leukemia and analyses all the aspects of the different therapeutic strategies. Data, for this analysis were obtained from the Italian Cooperative Group's Studies and from other published series. Special attention was given to the impact of splenectomy, alpha-interferon therapy and new drugs such as purine analogues (2-CdA, 2-dCF) on the management of the disease. The last section concerns minimal residual disease, second neoplasia and the most common causes of death. A whole paragraph is dedicated to hairy-cell leukemia variants. PMID- 8511397 TI - The hexon genes of adenoviruses of subgenus C: comparison of the variable regions. AB - We report on a 1402-base pair long DNA sequence, encoding for the variable region and parts of the flanking conserved regions of the human adenovirus type 1 (AV1) hexon, and a DNA sequence comprising 1396 base pairs, encoding for the corresponding regions of the human adenovirus type 6 (AV6) hexon. AV1 and AV6, together with AV2 and AV5, belong to subgenus C. Comparison of the predicted amino acid sequences of AV1 and AV6 with those of AV2 and AV5 revealed that the variable hexon region could be subdivided into highly variable, variable and conserved regions. Regions differing between AV2, AV5, AV1 and AV6 were the same as those which were registered as different when comparing AV40 and AV41 (subgenus F), suggesting that these areas of the hexon protein represent type specific antigenic determinants. Alignment of the amino acid sequences to the known 3-dimensional structure of the AV2 hexon demonstrated that the major amino acid changes were located in the L1 and L2 loops that form the surface of the hexon. Comparison of sequencing data between the serotypes might elucidate questions concerning evolution within subgenus C. PMID- 8511399 TI - Effect of natural and semisynthetic polymers on rabies virus infection in CER cells. AB - Different natural and semisynthetic polymeric carbohydrates inhibited rabies virus infection in chicken-embryo-related cells by interfering with the virus adsorption process; a dose-dependent relationship was exhibited. Among polysaccharides tested, the neutral polymer Scleroglucan and the negatively charged Keltrol, glyloid sulphate 4324, glyloid sulphate 4327 and alginic acid were the most effective and remained active at concentrations far below the cytotoxicity threshold. Data obtained indicated that the inhibition mechanism of polymers may be related to the ability of these compounds to bind to viral envelopes, although their interaction with cell surfaces cannot be excluded. The charge density and the polymeric backbone of the molecules seem to play a role in influencing the antiviral properties, whereas other features such as the sugar moieties do not appear to be relevant. PMID- 8511398 TI - Structural gene products and morphogenesis of a hybrid between rubella virus and a hamster latent retrovirus. AB - We studied the structural gene products and morphogenesis of the hybrid between rubella virus (RV) and a latent retrovirus (R-type virus or R virus) of a baby hamster kidney cell line, BHK21/WI-2. In electron microscopic analysis, the rubella virion measures 80 nm in diameter and has a round nucleoid form with an electron-lucid centre, while R-type virus is 110 nm in diameter and has a round nucleoid with radial spokes. The type 2 hybrid (H2) virion is pleomorphic, ranging from 85 to 110 nm in diameter, and has a nucleoid structure similar to R virus, with short spokes. Indirect immunofluorescence staining of H2-infected cells with polyclonal and monoclonal antibodies (mAb) against the RV structural proteins demonstrated expression of the homologous RV gene products. SDS-PAGE of 35S-methionine-labelled proteins in RV- and H2-infected cells revealed that they both produce four major immunoprecipitable proteins, three of which (E2a, E2b and C) are products of the two genetic homologous loci (e2 and c). In nonhomologous regions, RV-infected cells exhibited E1 protein, while H2-infected cells produced the Env protein of R virus. Western immunoblotting analysis of RV and H2 viral proteins with mAb confirmed that H2 virions carry rubella viral E2 and C proteins and that E1 protein is carried by RV but not H2 virion. These results explained the absence of serological cross-neutralization of haemagglutination and plaque forming ability of RV and H2 viruses. PMID- 8511400 TI - Pre-core mutation associated with lack of hepatitis B e antigenaemia in Moroccan asymptomatic carriers of the virus. AB - Recently, ongoing chronic liver disease with persistent viraemia has been described in hepatitis B virus (HBV) carriers despite the presence of anti-HBe. This has been attributed to infection with pre-C-region-mutated HBV variants. To investigate the possible existence and the prevalence of HBV variants in Morocco and the correlation between HBV DNA detection by polymerase chain reaction and pre-S1 antigenaemia, we tested twenty blood donors, HBsAg chronic carriers for more than one year. The diagnosis of such HBeAg-negative HBV variants was determined by a previously described rapid detection method using selective oligonucleotide hybridization. Probes M0, M1 and M2 correspond, respectively, to a non-mutated distal pre-C sequence, a one-point-mutated sequence with a TAG stop codon at pre-C codon 28 and a two-point-mutated sequence with codon 28 TAG and codon 29 GAC. All the 5 HBeAg-positive samples hybridized with the M0 wild-type probe only. Among the anti-HBe-positive samples, one hybridized with the M0 probe only, whereas another hybridized with none of the oligoprobes. The 13 remaining HBeAg-negative cases hybridized with the M1, M2 or combined M0, M1 and M2 probes. Seven of the 13 HBeAg-negative samples hybridized with more than one probe. DNA sequencing confirmed mixed distal pre-C sequence changes in samples hybridizing with more than one probe. These data demonstrate the existence, in patients, of HBV variants containing an inactive pre-C region and hence the incapacity to synthesize pre-C-region-derived HBeAg. PMID- 8511401 TI - Polio vaccines and the origin of AIDS. PMID- 8511402 TI - Oxygen and avian eggshell formation at high altitude. AB - Many birds at high altitude lay eggs with reduced eggshell diffusive conductance to water vapor. Disagreement exists about the cause, but hypotheses include physiological acclimatization and genetic adaptation. To investigate this, we tested for the occurrence of physiological acclimatization and quantified the effect of relieving hypoxia at high altitude. Ten laying hens (Gallus domesticus) were exposed to elevations of 3800 m (PIO2 90 Torr), 3800 m with supplementary oxygen (PIO2 140 Torr), and 1200 m (PIO2 125 Torr). 573 eggs were collected and analyzed during the 17-week experiment. Shell conductance, aggregate pore area, and shell thickness were reduced at 3800 m compared to 1200 m or 3800 m with supplementary oxygen. There was a lag in the response to changes in altitude or PIO2 that corresponded to a time constant of approximately 2.5 weeks. We conclude that physiological acclimatization of eggshell conductance occurs in some chickens, and that it is probably stimulated by hypoxia. PMID- 8511403 TI - Active Na+ transport and coupled liquid outflow from hydrothoraces of various size. AB - The net rate of liquid flow and Na+ flux across the pleura was determined in anesthetised rabbit during hydrothoraces 0.5 to 5 ml in size, without and with amiloride. In the hydrothoraces with amiloride the net liquid flow and Na+ flux reversed when the volume injected approached zero. This indicates that the active Na+ transport and the consequent liquid absorption occur also under physiological conditions. The difference between the data obtained without and with amiloride provides the net solute-coupled liquid outflow and active Na+ efflux. These parameters increased linearly with the hydrothorax size up to 2 ml (0.39 ml/h and 54 muEq/h, respectively), and then levelled off. The linear relationship allowed their extrapolation to physiological conditions: 0.15 ml/h (0.07 ml.h-1.kg-1) and 21 muEq/h (0.1 muEq.h-1.cm-2). The increase in these parameters with the hydrothorax size seems due to the protein dilution caused by the Ringer injection, because it did not occur if Ringer was added with albumin to keep the protein concentration in the pleural liquid similar to that under physiological conditions. PMID- 8511404 TI - Hypoxia, sleep and respiration in relation to opioids in developing swine. AB - To test the role of mu and delta opioid systems in neonates during hypoxia, a total of sixteen, 4-11 (n = 7) and 26-33-day-old piglets (n = 9) were instrumented aseptically for assessment of sleep/wake states (S/W), electromyographic activities of the diaphragm and posterior cricoarytenoid muscles (EMGdi, EMG-pca, respectively), heart rate, and arterial pressures, pH and gas tensions. During daily sessions for 5 consecutive days, the piglets inhaled 10% O2/90% N2 for 10 min twice per session, first before any drug, then after either naltrexone (2 mg.kg-1 i.v.), a predominantly mu opioid antagonist, or naltrindole (4 mg.kg-1 i.v.), a specific delta opioid antagonist. During hypoxia, young, in contrast to older piglets, spent more time asleep, and increased sleep during the second half of the hypoxic exposure before, but not after each antagonist. They also exhibited, overall, higher breathing frequency, and lower slope, amplitude, area and initial area of EMGdi and EMGpca activity than older piglets. Naltrindole stimulated EMGpca activity in both age groups, and naltrexone increased the breathing frequency and slope of EMGdi in the older group. We conclude that hypoxia enhances the activation of central mu and delta opioid systems which influence S/W and respiration. PMID- 8511405 TI - Axon reflex in resiniferatoxin-induced bronchoconstriction of guinea pigs. AB - To study the role of the axon reflex in resiniferatoxin (RTX)-induced bronchoconstriction in vivo, 32 guinea pigs weighing 292 +/- 7 g were randomly divided into five groups: Group 1, control (n = 6); Group 2, chlorisondamine (n = 6); Group 3, tetrodotoxin (TTX, n = 6); Group 4, local capsaicin application (n = 6); and Group 5, systemic capsaicin application (n = 8). Chlorisondamine was used to interrupt ganglionic transmission while TTX was employed to block nerve impulse conduction. In Group 4, capsaicin was locally applied to both cervical vagus nerves 30 min prior to the study whereas capsaicin was given subcutaneously for 5 days starting 9 days before the study in Group 5. Each animal was anesthesized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and artificially ventilated. All the above animals were treated with atropine (0.2 mg/kg) and phenoxybenzamine (0.5 mg/kg). Resiniferatoxin (2 micrograms/kg) was injected intravenously to induce airway constriction. Immediately upon injection of RTX (at 1 min), each animal in the control group exhibited decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, indicating severe bronchoconstriction. Then the airway spasm ameliorated gradually with time. Animals in Groups 3 and 4 indicated partial abolishment, while those in Group 5 showed complete abolishment, of the RTX-induced bronchoconstriction. On the other hand, the animals in Group 2 did not display any significant alteration in the RTX-induced bronchospasm. Furthermore, we tested RTX-induced bronchoconstriction in 5 additional animals not pretreated with either atropine or phenoxybenzamine. Compared with the data above, no significant differences in RTX-induced respiratory changes were found. Since it is known that TTX blocks nerve conduction, the data suggest that the TTX sensitive reflex (the axon reflex) via afferent C-fibers plays a significant role in the RTX-induced bronchoconstriction, which is apparently mediated via tachykinins. PMID- 8511406 TI - Does snoring intensity predict flow limitation or respiratory effort during sleep? AB - We tested whether snoring sound intensity could be an accurate predictor of the degree of respiratory effort or the decrease of inspiratory volume during partially obstructed breathing in sleep. Six snorers were investigated with nocturnal polygraphic monitoring including measurement of esophageal pressure (Pes), airflow (pneumotachometer and face mask, indicating tidal volume [VT]), and snoring sound intensity (SSI) measured in decibels. SSI was a poor predictor of flow limitation during snoring. Considerable between- and within-subject variance did not allow establishment of models for the interdependence between VT and SSI. The increase in peak-negative inspiratory efforts was better predicted by SSI. Individual multiple correlation analyses of Pes on SSI indicated a positive interdependence in all subjects. Calculation of ecological correlations with subject means of Pes and SSI was performed. SSI significantly predicted the level of peak-negative inspiratory effort during obstructed, noisy breathing for a given subject. Monitoring of snoring sound intensity may be a useful indicator identifying subjects performing high peak negative inspiratory efforts with obstructed, noisy breathing during sleep. PMID- 8511407 TI - Respiratory electromyographic estimates of ventilatory functions in piglets. AB - The best electromyographic (EMG) predictors of respiratory drive (P100), tidal volume (VT) and ventilation (VE) were determined from diaphragmatic (DI) and posterior cricoarytenoid (PCA) EMG measures in 8-48-day-old, anesthetized piglets. Progressive hypercapnia was employed to obtain a wide range of muscle activity. A custom-designed, microcomputer-based system was employed to measure the duration, peak amplitude, rate of rise (initial slope) as well as the summed total and initial (first 100 ms) EMG activity from the DI and the PCA. For each respiratory function, the following combinations of EMG measures were identified as significant predictors using regression analyses: (1) for P100, DI amplitude, PCA initial area and PCA rate of rise; (2) for VT, DI amplitude, PCA duration and DI duration; (3) for VE, DI amplitude, DI initial area, PCA initial area, PCA rate of rise, PCA duration, DI area and DI rate of rise. Thus, whereas the traditionally employed measure of DI amplitude is an important correlate of P100, VT or VE, a complete estimate of these respiratory functions requires the inclusion of initial EMG measures and duration. PMID- 8511408 TI - Inhibition of respiratory activity during passive ventilation: a role for intercostal afferents? AB - The purpose of this study was to determine whether receptors from the rib cage are primarily responsible for inhibitory feedback of inspiratory muscle activity during mechanical ventilation. Seven quadriplegics with C5-C6 lesions were compared to 6 normals during mechanical ventilation. All subjects were mechanically hyperventilated with a nasal mask to suppress intrinsic inspiratory muscle activity. End-tidal partial pressure of carbon dioxide (PETCO2) was increased by either adding CO2 (FICO2) or decreasing tidal volume (VT) until reoccurrence of inspiratory activity, defined as the recruitment threshold (PCO2RT). The difference between PCO2RT and eupneic PETCO2 indicated the presence and magnitude of volume-related inhibition of inspiratory muscle activity during mechanical ventilation. Substantial inhibition of inspiratory activity was observed in both quadriplegics and normals. We conclude that afferent information from the rib cage is not obligatory for the mediation of volume-related inhibition of inspiratory muscle activity during mechanical ventilation. PMID- 8511409 TI - Pharyngeal dilator muscle contractile and endurance properties in neonatal piglets. AB - Pharyngeal dilator muscles are critical for maintaining upper airway patency in the neonatal period. The present study examined in vitro the contractile properties of a pharyngeal dilator muscle, the sternohyoid, in 1-7-day-old piglets (n = 24). Isometric contraction and half-relaxation times were 36.7 +/- 1.1 and 30.9 +/- 1.2 msec, respectively. Twitch potentiation ('staircase phenomenon') and post-tetanic potentiation were noted following repetitive stimulation. During prolonged repetitive stimulation with a standard (40 Hz) fatigue test, muscle force declined gradually over time, with loss of half of the initial force occurring over 138 +/- 11 sec, and a 2-min fatigue index (ratio of force at 2 min to initial force) of 0.52 +/- 0.03. An additional 10 piglets were studied at ages of 14-20 days. Muscle from older piglets had comparable isometric twitch kinetics as that of younger animals. However, sternohyoid muscle from the older piglets had worse endurance than muscle from the younger animals, as indicated by a shorter time required for force to decrease by half (86 +/- 10 sec, P < 0.01) and a lower 2-min fatigue index (0.36 +/- 0.03, P < 0.01). These data indicate that for the sternohyoid muscle of the newborn piglet (a) physiological properties are consistent with moderate to fast contraction with good endurance, (b) force potentiates during repetitive twitch stimulation and following a brief period of tetanic stimulation, and (c) there is worsening of endurance but no change in isometric twitch kinetics with increasing age during the first weeks of life. PMID- 8511411 TI - Electrophysiologic studies in the newborn. PMID- 8511410 TI - Clinical neurologic examination of the preterm and term neonate. PMID- 8511412 TI - Neurologic trauma in newborn infants. PMID- 8511413 TI - Brain death in neonates. PMID- 8511414 TI - Baby Dough, baby Wray, baby me. PMID- 8511415 TI - Neuroimaging of the neonate. PMID- 8511416 TI - Hypoxic-ischemic brain injury in the newborn. PMID- 8511417 TI - Intraventricular hemorrhage of the preterm infant. PMID- 8511418 TI - Diagnosis of neonatal seizures. PMID- 8511419 TI - Treatment of neonatal seizures. PMID- 8511420 TI - Diagnosing inherited metabolic encephalopathies in neonates. PMID- 8511421 TI - Toxic encephalopathy in the newborn. PMID- 8511422 TI - Neonatal hypotonia. AB - The approach to a newborn with hypotonia should not differ substantially from that to an older patient. The examination may be more difficult to interpret, especially in evaluating mental status and muscle strength. However, laboratory studies such as serum enzymes, EMG, and muscle biopsy may be very specific in helping the neurologist to arrive at a diagnosis, even in premature infants. PMID- 8511423 TI - Macrocrania and megalencephaly in the neonate. PMID- 8511424 TI - Deterministic role of the cell cycle in newborn brain development and in brain injury. PMID- 8511425 TI - Action of the cerebello-thalamo-cortical projection upon visually initiated reaction-time hand movements in the monkey. AB - Electrophysiological characterization of thalamo-cortical projections and cerebello-thalamo-cortical pathways was shown by acute experiments in which laminar field potential analysis of responses evoked in the cortex by stimulation of thalamic and cerebellar nuclei was performed in anesthetized monkeys. Based on the results, dynamic activities of cerebro-cerebellar interconnections on voluntary movements were recorded with electrodes chronically implanted in various cortical areas in unanesthetized monkeys and were correlated with their behaviours. Cortical field potentials change in learning processes of visually initiated reaction-time hand movement and in compensating processes after cerebellar hemispherectomy. PMID- 8511426 TI - What goes on in the motor thalamus? AB - Physiological observations made in man offer a unique opportunity to understand the motor thalamus. On the one hand, the patient can describe what he feels when a site is stimulated; on the other, one can observe any induced motor effect, both in 'normal' patients and in those with movement disorders. Finally, all this can be correlated with single unit recordings at the same site. Data has been correlated relative to the motor thalamus from over 10,000 macrostimulation sites and from 114 patients undergoing microstimulation and microrecording, in an attempt to understand something of the function of this part of the brain. PMID- 8511427 TI - Three-dimensional electrophysiological atlas created by computer mapping of clinical responses elicited on stimulation of human subcortical structures. AB - A computer-generated three-dimensional functional atlas, based on clinical responses elicited upon electrical stimulation of subcortical structures of awake patients during stereotactic functional neurosurgery is presented, which shows a characteristic distribution pattern of motor, sensory and autonomic or emotional responses, respectively. The computer system used in this study is capable of accumulation and processing of data with three-dimensional coordinates, which can be converted to an anterior commissure-posterior commissure coordinate (AC-PC) system, and displays the processed data three-dimensionally together with a three dimensional atlas created by interpolation of the Schaltenbrand-Bailey's atlas for standard anatomical landmarks. PMID- 8511428 TI - Tremor-mediating thalamic zone studied in humans and in monkeys. AB - The thalamic zone mediating the rhythmic burst activity related to the contralateral tremor was studied by microelectrodes in clinical cases with tremor and in monkeys with experimental tremor. The rhythmic burst time-locked with the tremor was found in a restricted area of the ventrointermedius nucleus (Vim) in humans and also in VPLo nucleus in monkeys. In both cases, only the lateral and ventrocaudal part of each nucleus, which was defined as the kinesthetic zone, was involved. A possible tremor-mediating neural circuit is postulated. PMID- 8511429 TI - Thalamic neuronal populations responding selectively to remembered words. AB - In 16 Parkinson patients treated with implanted electrodes, the multiunit impulse activity of 165 neuronal populations was recorded as a part of the diagnostic procedures during the performance of a set of verbal psychological tests. 10 neuronal populations in the thalamus revealed selective responses to visual presentation of the target words remembered prior to the test or to the presentation of both the target words and of the words closely resembling the targets graphically. PMID- 8511430 TI - Tremor and skeletal muscle tone. AB - Stereotactic interventions at thalamic/subthalamic levels for parkinsonian tremor give the chance to investigate the influence of the supraspinal proprioceptive loops on the tonic component of motor tasks. Studies demonstrate not only a normalization of the late stretch reflex component and a decrease of the pre reflex stiffness in muscles contralateral to the side of the lesion, but also a reduction of low threshold motor unit firing frequency in the elbow flexors during isometric contractions. These data indicate a shift from a more tonic to a more phasic mode of innervation, which we interpret as the cause of hypotonia. PMID- 8511431 TI - Input-output organization of the ventrolateral nucleus of the thalamus. AB - Input-output organization of the ventrolateral nucleus (VL) of the thalamus was analyzed electrophysiologically and morphologically at the single cell level. Virtually all pyramidal tract neurons in the motor cortex and area 6 received convergent inputs from the dentate (DN) and the interpositus (IN) nuclei and about 60% of thalamocortical (TC) neurons received convergent inputs from both the DN and the IN. Anterograde labelling following focal injection of Phaseolus vulgaris leukoagglutinin and intracellular staining of TC axons showed that the terminals in layer III tended to aggregate into patches about 1-1.5 mm wide in a frontal plane, which were arranged in longitudinal strips about 2-5 mm long in a rostrocaudal direction. PMID- 8511433 TI - Comparative anatomical study of ventrolateral thalamic mass in humans and monkeys. AB - Cytoarchitecture and enzyme activity in the ventrolateral thalamic mass of humans and monkeys were examined using conventional Nissl, myelin stain and histochemical methods. According to the data obtained from cytometric analysis, the histogram patterns of cell dimensions and cell density in each ventrolateral thalamic nucleus in humans and monkeys were very similar. Moreover, acetylcholinesterase-stained sections revealed a parcellation of the ventrolateral thalamic nuclei that could be correlated with that in the monkey thalamus. Apart from differences of size, the nuclei of the human and monkey thalamus are remarkably similar. We proposed accordingly that a new parcellation of human thalamic nuclei be based on cytometric analysis and histochemical staining. PMID- 8511432 TI - The primate motor thalamus analysed with reference to subcortical afferent territories. AB - This paper analyses the internal organisation of the primate motor thalamus. A topographic study of the three main subcortical afferent territories (the cerebellar, pallidal and nigral territories) gives a much simpler and more functionally relevant partitioning of the thalamus than consideration of conflictual cytoarchitectonic nuclei. PMID- 8511435 TI - Cerebello- and pallido-thalamic pathways to areas 6 and 4 in the monkey. AB - Projections from the cerebellar nuclei (CN) and the internal segment of the globus pallidus (GPi) to areas 6 and 4 via the thalamus were examined electrophysiologically in monkeys. In addition to the well-known pallido-thalamo cortical projection to area 6, some thalamic neurons with CN input were found to project to area 6. Seventeen neurons in VLc, area X and the dorsal margin of VPLo were activated antidromically by stimulation of supplementary motor or premotor areas, and orthodromically by CN stimulation. Twelve neurons in area X and the medial part of VPLo were found to receive CN input and to project to the arcuate premotor area (APA). Four neurons in the VLo-X border region which were identified to project to APA were inhibited by GPi stimulation. PMID- 8511434 TI - Anatomical distinctions between the two basal ganglia afferent territories in the primate motor thalamus. AB - In primates, the efferents of the two basal ganglia output structures, medial globus pallidus and substantia nigra pars reticularis, are completely segregated and target different thalamic regions. Despite similarities demonstrated earlier in non-primate species in the functional properties and ultrastructural features of the terminals of the two pathways, the present findings suggest significant differences between thalamic circuits associated with the two systems in primates. The data presented in this report further support the concept on functional and anatomical diversity of the subdivisions of the primate motor thalamus proposed in 1990 by Hinsky. PMID- 8511436 TI - Stereotactic thalamotomy for dystonic patients. AB - A total of 54 patients (22 females and 32 males) with dystonia underwent thalamotomy. These patients consisted of 25 dystonia musculorum deformans (DMD) and 29 secondary dystonia cases. All of the patients were analyzed prospectively. Preoperative and postoperative symptoms were compared and grade. The target areas of thalamotomy were the ventral intermediate (Vim) and posterior ventral oral (Vop) nuclei. 59% of the patients showed more than 25% improvement, 23% were slightly improved cases (less than 25%), and 16% showed no change or their symptoms had worsened. PMID- 8511437 TI - Unit activity of nucleus ventralis lateralis of human thalamus during voluntary movements. AB - The dynamics of change of single VL neurons of human thalamus during voluntary movements was investigated in the course of stereotactic operations on dyskinetic patients. Two basic types of units (A and B cells), reacting to the voluntary movement with different discharge patterns, revealed the common dynamics and a transient time-connectivity of responses correlated with certain phases of the performance of motor acts. It is supposed that these findings reflect the dynamic conjugation of two functionally different cellular subsystems in the human thalamus, which perform collaborative processing and transmitting of information during voluntary movements. PMID- 8511438 TI - Role of the thalamus in parkinsonian tremor: evidence from studies in patients and primate models. AB - The electrophysiologic basis of parkinsonian tremor is discussed in terms of the central oscillator and peripheral feedback hypotheses of tremor. Recent studies in monkeys and humans suggest that parkinsonian tremor may result from the activity of a central oscillator, possibly located in the basal ganglia. Peripheral somatosensory input seems to modulate tremor and central nervous system activity related to tremor. PMID- 8511439 TI - Use of backcalculation for estimation of the probability of progression from HIV infection to AIDS. AB - Backcalculation has been used to estimate the rate of past HIV infection and to predict future AIDS incidence. In this study we examine another use: estimating the probability of progression from HIV infection to AIDS as a function of time from infection. Given observed AIDS incidence data, the technique of backcalculation estimates the most likely number of persons infected with HIV in the past. Assumptions about probability of progression from HIV infection to AIDS are necessary. By varying these assumptions and examining the resulting goodness of fit to the AIDS incidence data, we can theoretically estimate parameters of progression. We report on implementation of this method and examine its practical utility in deciding among four competing progression models specified on a priori grounds. The four specific models comprise three Weibull distributions with medians of 8, 10, and 12 years, respectively, and one model that begins as a Weibull with 8 year median but where the hazard is level after 3.5 years. To employ asymptotic maximum likelihood methods, we define a two parameter family of progression models that includes all four a priori models. One parameter sets the scale for an initial Weibull progression (the shape parameter being fixed for all models), and the other specifies a levelling point after which the hazard remains constant. AIDS incidence data from Canada's national surveillance system provided the empiric data for this evaluation. First we corrected these data for reporting delay by Poisson modelling of the delay distribution. We used three parametric families of infection curves: step-function, log-logistic, and logistic. The results support the hypothesis of an early levelling of the hazard function. When we fixed the scale parameter to that of the Weibull curve with 8 year median, the maximum likelihood estimate of the levelling point was 2.7 years, and a clearly superior fit was produced compared to a pure Weibull progression with the same scale parameter (likelihood ratio chi-square of 10.6 on 1 degree of freedom, p = 0.001). The maximum was indistinguishable in fit from the levelling point of 3.5 years hypothesized in advance (chi-square = 0.30, d.f. = 1, p = 0.58). Backcalculation, however, could not determine the Weibull scale parameter itself because the likelihood was quite flat as a function of this parameter. We conclude that one must determine the parameters governing the initial shape of the hazard function from other kinds of data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8511440 TI - Using orthogonal polynomial scores in summarizing and evaluating longitudinal data collected in phase I and II clinical pharmacology studies. AB - Orthogonal polynomial scores (OPS) is a simple, biologically meaningful approach to characterize longitudinal data in phase I and II clinical pharmacology trials. It describes average, linear, quadratic and higher order polynomial characteristics of each subject's response over time with use of composite scores computed from linear combinations of the observed data. The statistical evaluation of the composite scores is univariate. For studies with a small number of experimental units and with many repeated measures, OPS may offer advantages over the use of summary measures such as the maximum response (MAX), the time at which MAX occurred (TMAX), or the area under the response curve (AUC), and other popular approaches such as time-point-by-time-point, split-plot, and multivariate analyses. PMID- 8511441 TI - Two-stage tests for studying monotherapy and combination therapy in two-by-two factorial trials. AB - Two-stage testing involves a preliminary test of a nuisance parameter prior to testing a main hypothesis. In a two-by-two factorial trial, the treatment interaction is the nuisance to the inference about the efficacy of one of the treatments given alone. In comparing a combination therapy to both of its component therapies, the nuisance parameter is the difference in the component effects. When the preliminary test is an integral part of inference about the main parameter, the actual level of significance for the two-stage test procedure can be much higher than the desired nominal level. If one places no restriction on the value of the nuisance parameter, then any two-stage test with its significance level properly controlled has undesirable properties. This applies to comparative studies of combination agents relative to the component agents. When the interaction with an ineffective treatment is null, two-stage testing may have some power advantage for assessing monotherapy efficacy. PMID- 8511442 TI - Markov chain modelling of bioassay toxicity procedures. AB - Many bioassay procedures to test a new substance for toxicity, like some phase I clinical trials, can be modelled as first-order Markov chains with absorbing states. We provide a general framework for such procedures. We show how one may calculate under any dose response curve assumption final absorption probabilities, and a number of total average costs such as time required until trial completion, number of subjects treated, number of subjects exhibiting unacceptable levels of toxicity, and amount of medication administered. One may use the above information associated with the trial for an a priori comparison between competing designs under consideration. We provide an example of such a comparison. PMID- 8511443 TI - P-values after repeated significance testing: a simple approximation method. AB - The P-value after a repeated significance test is a useful measure of the strength of evidence against the null hypothesis. Its computation, however, requires a computer-intensive numerical integration method. The P-value is not conceptually straightforward, because it depends on how the sample space is ordered, which can be arbitrary. We look at two orderings of the sample space, one proposed by Tsiatis et al. and the other by Rosner and Tsiatis, and Chang. Although studies have shown that the latter ordering gives more reasonable confidence intervals than the former, the former gives a conservative and therefore more reasonable P-value. Both, however, should yield an identical P value in most applications. In this paper we present a simple method of approximating P-values. We provide tables to implement the method for two to ten stages with alpha = 0.1, 0.05 and 0.01 for the Pocock and O'Brien-Fleming procedures. The proposed method can be applied to both orderings. PMID- 8511444 TI - Confidence limits based on the first occurrence of an event. AB - Confidence limits for population prevalence based on the first occurrence of an item in a medical database, or for incidence based on time to first occurrence, should be based on the geometric or exponential distributions, respectively. These intervals are presented and compared with the corresponding intervals based on the binomial and Poisson distributions. The lower confidence limits are shown to be the same, but the upper limits are smaller, hence leading to shorter intervals. Applications of these intervals are also presented. PMID- 8511445 TI - Sample size and power for prospective analysis of relative risk. AB - In a placebo-controlled vaccine efficacy trial or a trial of equivalence of vaccines, one may wish to show that relative risk of disease is less than a specified value R0, not equal to one. This paper compares three methods for estimating relative risk in the binomial setting, based on a logarithmic transformation, likelihood scores, and a Poisson approximation. Exact power and size of test are calculated by enumeration of possible binomial outcomes, and power is approximated from asymptotic formulations. Although the score method is generally preferable, for most studies of practical interest the log and score methods are comparable, and the Poisson method is also appropriate for small risks, up to about 0.05. When true and null relative risks are less than one, unequal allocation of study individuals can increase power, and the asymptotic formula for the log method may substantially underestimate power; in such a study the power approximation for the score method is more reliable, even if the log method is used in analysis. Exact power calculations are helpful in planning studies. The log and Poisson methods, but not the score method, apply readily in the case of unequal follow-up. PMID- 8511446 TI - Exact conditional and unconditional sample size for pair-matched studies with binary outcome: a practical guide. AB - Tables of sample sizes for pair-matched studies with binary outcome are presented. They are based on conditional and unconditional approaches using the 'exact' (binomial) test. An approximate procedure is suggested to estimate the sample size for parameter values that do not correspond exactly with table entries. The procedure utilizes a minor modification of the large-sample formula given by Connett et al. A practical strategy for estimating the overall sample size in the presence of a nuisance parameter (the proportion of discordant pairs) is recommended. An example from a proposed clinical trial is given. PMID- 8511447 TI - [What is your roentgen diagnosis? Spontaneous arthrodesis of the left hip joint following TB-coxitis during the growth years]. PMID- 8511448 TI - [The first successful lung resection]. AB - In 1883 Kronlein resected a sarcoma of the ribs in an 18 year old female. Six months later he reoperated the patient for a local recurrency. At the second operation which necessitated a wide exposure of the thoracic cavity he deliberately removed a pulmonary metastasis about the size of a walnut. Two years later a new recurrence had to be resected. The three interventions led to a survival of 7 years. The patient succumbed to a further recurrence in 1890. Kronleins operation opened two new chapters in surgery, pulmonary interventions in general and in particular surgery of pulmonary metastasis. Surgery of lungs was not a topic of that era, particularly since some incisions for abscesses and resections of pulmonary parenchyma had not been successful. By limiting the indication to patients with sufficient pulmonary function and by following the successful pneumonectomy experiments in animals Kronlein favored pulmonary resection. The success of this intervention confirmed these considerations especially since it lasted for years. It was followed in 1885 by a pulmonary resection by G. Ruggi in Bologna. Surgery of the lung, however, came in general use only 50 years later. PMID- 8511449 TI - [Cocaine and alcohol: an explosive cocktail!]. AB - Cocaine is a powerful reinforcer that has become a popular drug of abuse. Cocaine inhibits the reuptake of dopamine into presynaptic terminals, resulting in an overstimulation of the dopaminergic system. When cocaine and alcohol are taken together, cocaine is partially converted by a liver carboxylesterase to its ethyl homolog called ethylcocaine. In 1991, several studies demonstrated that ethylcocaine is a pharmacologically active metabolite of cocaine. Ethylcocaine was shown to be even more potent than cocaine in mediating lethality. In the USA, prevalent studies have indicated that concurrent and simultaneous abuse of cocaine with alcohol were a very common practice. In Switzerland, as far as we know, epidemiologic studies have not been carried out yet. In our laboratory, radioimmunoassays mainly sensitive to benzoylecgonine (an inert metabolite of cocaine and ethylcocaine) are used to detect cocaine abusers. Positive results are always confirmed by combined gas chromatography (GC) and mass spectrometry (MS). Recently, cocaine, ethylcocaine, methyl ecgonine and ethyl ecgonine were detected by GC/MS in urine from three people arrested after erratic driving. Their blood alcohol concentration was 2.89, 0.98 and 1.26 g/kg. In Switzerland, the influence of alcohol, cocaine and ethylcocaine on the incidence of accidents, overdose and death is not known and requires further studies. Because morbidity and mortality are exacerbated by concurrent use of alcohol and cocaine, physicians should discourage their hooked patients from consuming this deadly mixture. PMID- 8511451 TI - [Professor Sauerbruch and the honorarium]. AB - Wherever the successful surgeon, Ferdinand Sauerbruch, worked, headlines about his incredible fees appeared in the press. In 1912 and 1913, even the Zurich Cantonal Parliament investigated an alleged scandal regarding excessive fees demanded by Sauerbruch. However, the allegations were quickly proven false by the medical faculty and the accused himself. Nevertheless, the affair made headlines once again in 1931, which led to a clarifying exchange of letters between the rector of the University of Zurich and the surgeon, who was then working in Berlin. PMID- 8511450 TI - [Multimodal imaging exemplified by gluteal abscesses--a case report]. AB - The detection of occult abscesses can draw a long chain of diagnostic procedures as the procedures as the presented case documents. Next to conventional X-ray studies and examination by ultrasound scintigraphy is available. Studies of the skeleton by the latter using phosphonates for osteomyelitis or 111-I-labeled neutrophils or 99m-Tc-labeled monoclonal antibodies against neutrophilic surface antigens for the detection of abscesses in soft tissues are of recent interest. MR-imaging is used for preoperative planning after successful detection. PMID- 8511452 TI - [Mrs. H.'s dilemma. Description of a patient situation in the intensive care unit, observations and consequences]. AB - "The dilemma about Mrs. H." describes an ethical conflict centering around the theme of patient-restraint, an ethical dilemma the author has experienced with a patient on the emergency ward. The question whether the safety of the patient is more important than her autonomy is posed. In discussions with the care team solutions are sought that can be realized subsequently to a great part. It is furthermore shown that many conflicts of nurses caring for patients may not be solved but at least better coped with by discussions and reflections. PMID- 8511453 TI - [A case from practice (267). 1. Primary hyperparathyroidism--generalized pruritus -diffuse alopecia 2. Major depression according to DSM-III-R 3. Bilateral adrenal cortex adenoma 4. Chronic obstructive lung disease]. PMID- 8511454 TI - [A trip through the vitamins]. PMID- 8511455 TI - [What policy in the matter of mental health?]. PMID- 8511456 TI - [Understanding and caring for psychic suffering]. PMID- 8511457 TI - [When will we have a more humane psychiatry?. Interview by Ria Frick]. PMID- 8511458 TI - [Port of call at Orly .... Interview by Odile Burrus]. PMID- 8511459 TI - [Computer screens, vision and ... company]. PMID- 8511460 TI - [The utility of the "nursing care report"]. PMID- 8511461 TI - [No pity for staphylococci!]. PMID- 8511462 TI - [The demand for nurses and midwives]. PMID- 8511463 TI - [The emergency room, you either love it ... or you don't love it!]. PMID- 8511464 TI - [At the Rennes Regional Hospital Center, is the nurse confident with the vitally distressed patient?]. PMID- 8511465 TI - [The role of the psychiatric nurse in an emergency service]. AB - Since september 1989, 3 psychiatric nurses have been working with the crisis and psychiatric emergencies unit of the emergency service of Saint-Luc Hospital in Brussels (Belgium). In this paper, the authors examine the specific functions of psychiatric nurses in the taking in charge of psychiatric emergencies and functional somatic complaints, as well as their role in relation with the nursing team as a whole. PMID- 8511466 TI - [Attempted suicides in the emergency service]. PMID- 8511467 TI - [Preparation of infusions]. PMID- 8511468 TI - [Detailed procedure for insertion of central catheters]. PMID- 8511469 TI - [Professional staff committees and organization of care]. PMID- 8511470 TI - [Adolescents and chronic illnesses: a nurse's experience]. PMID- 8511471 TI - [Gastrointestinal surgery via laparoscopy]. PMID- 8511473 TI - [Atmospheric pollution: a menace for health in the largest cities of the world]. PMID- 8511474 TI - [The hospital room: functionalism and estheticism]. PMID- 8511472 TI - [Tetany]. PMID- 8511475 TI - [Acute cranial traumas: physiopathology and practical management in the first 48 hours]. PMID- 8511476 TI - [The role of the nurse in the management of cranial traumas in the initial phase]. PMID- 8511477 TI - [The role of the physical therapist in the rehabilitation of severe cranial trauma in the initial phase]. PMID- 8511478 TI - [Severe cranial trauma in the rehabilitation milieu. Management in the initial phase]. PMID- 8511479 TI - [Location signs in admission departments]. PMID- 8511480 TI - [Management of the hospitalized Parkinson patient]. PMID- 8511481 TI - [Tuberculosis, a pathology that has currently returned]. PMID- 8511482 TI - [Clear dressings for central catheters]. PMID- 8511483 TI - [Nosocomial infections of central catheters. Changing infusions]. PMID- 8511484 TI - [Alzheimer and similar disorders Association of France]. PMID- 8511485 TI - [The green house]. PMID- 8511486 TI - [Silence! ... We're rolling!]. PMID- 8511487 TI - [Weight loss, a major complication of AIDS]. PMID- 8511488 TI - [The role of the general practitioner in pathology due to AIDS]. PMID- 8511490 TI - [Transmission in the patient care team]. PMID- 8511489 TI - [Nurses in public hospitals: an aging population]. PMID- 8511492 TI - [Viral hepatitis ... a serious public health problem]. PMID- 8511491 TI - [Should we treat all the hypertensives?]. PMID- 8511493 TI - [Carbon monoxide poisoning]. PMID- 8511494 TI - [Results of an epidemiological survey of carbon monoxide poisonings in the Hauts de-Seine department]. PMID- 8511495 TI - [Bladder lavage]. PMID- 8511496 TI - Efficacy of twice daily doses of 40 or 20 milligrams famotidine or 150 milligrams ranitidine for treatment of patients with moderate to severe erosive esophagitis. Famotidine Erosive Esophagitis Study Group. AB - The comparative efficacy of twice daily regimens of 40 mg famotidine (group 1), 20 mg famotidine (group 2), and 150 mg ranitidine (group 3) was investigated in a double-blind randomized study of parallel groups of patients with endoscopically documented erosive esophagitis. Patients were enrolled at 29 centers in 19 countries and treated for 6 to 12 weeks until healing, defined as complete resolution of visible ulceration or erosion of the esophageal mucosa, demonstrated by repeat endoscopy. Healing occurred in 71% of 175 group-1 patients, 68% of 93 group-2 patients, and 60% of 172 group-3 patients; the difference between groups 1 and 3 was significant (P < or = 0.05). The three treatments produced similar levels of global symptomatic improvement and relief of daytime and nighttime heartburn. All treatments were well tolerated. These results support the hypothesis that reduction of esophageal acid exposure by 40 mg famotidine twice daily produces healing of lesions in patients with erosive esophagitis and is more effective than regimens that provide lesser reductions in esophageal acid exposure time. PMID- 8511497 TI - The significance of probe design in evaluation of colonic perfusion with laser Doppler flowmetry. AB - The significance of probe design for laser Doppler flowmetry measurement depth and variation was investigated by determining flux versus pressure relations and spatial variability with various probes placed on the serosal surface of porcine sigmoid colon. For two large probes (three optical fibers with diameter and center separation > or = 500 microns) the flux versus pressure relations showed autoregulation, indicating that the mucosal perfusion contributed to the flux signal. The curves were reproducible between individuals. With two smaller probes linear flux versus pressure relations were obtained, indicating a shallow measurement not influenced by the autoregulated mucosal perfusion. The spatial variation expressed as coefficients of variation of repeated recordings at each pressure level was significantly greater with the smaller probes (p < 0.001). For clinical use the larger probes should be preferred. These include all wall layers, and only 3 repeated recordings are needed to obtain a reproducible mean flux value within +/- 10%, as opposed to 10 with the smaller probes. PMID- 8511498 TI - Gastric acid secretion and pattern of gastroesophageal reflux in patients with esophagitis and concomitant duodenal ulcer. A multivariate analysis of pathogenetic factors. AB - This study was designed to assess the relationship between gastric acid output (GAO) and both pattern of gastroesophageal reflux (GER) and severity of esophageal lesions. Gastric acid secretory testing and 24-h intraesophageal pH monitoring were performed in 31 patients with esophagitis and concomitant duodenal ulcer (E+DU) and compared with those of 72 patients with esophagitis (E). The second aim of this study was to evaluate the role of GAO and other potential pathogenetic factors in the development of esophagitis. The results of the study showed that GAO in patients with E+DU was significantly higher than in patients with E (p < 0.05). There was no significant difference between the two groups of patients with regard to endoscopic findings or GER variables (p < 0.05). Multiple regression analysis with stepwise deletion showed that the presence of hiatal hernia, GER in the upright position and age appear to correlate significantly with the presence of esophagitis. We conclude that no parallel relationship exists between GAO and severity of GER or esophageal lesions in patients with E+DU and that GAO is not a major pathogenetic factor in GER disease. PMID- 8511499 TI - Enteric bacterial translocation after intraperitoneal implantation of rubber drain pieces. AB - To study the kinetics and mechanisms of bacterial translocation from the gut after intraperitoneal (IP) implantation of prosthetic materials, different sizes of rubber drain pieces were intraperitoneally implanted in the rat, followed by evaluation of ileal mucosal permeability after 2 days and of the occurrence of bacterial translocation and gut oxygen extraction at various time points. Enteric bacteria translocated to mesenteric lymph nodes and disseminated to systemic organs (liver, spleen, lungs, and kidneys), the portal vein, and inferior vena cava 2, 4, and 6 h after IP implantation of rubber drain pieces with 10-, 7-, and 3-cm2 areas, respectively, and subsequently to the IP rubber drain piece and the peritoneal cavity on the 2nd postoperative day. The incidence of translocation correlated with the size of the implanted material and time after implantation. The gut oxygen extraction increased significantly after IP implantation of 7- and 10-cm2 rubber drain pieces. The ileal mucosal permeability was enhanced in the groups implanted with 7- and 10-cm2 drain pieces. Thus, bacterial translocation occurs already in the early period after IP implantation of rubber drain and increased with time. The increased gut oxygen extraction implies that the gut is susceptible to IP inflammatory stimulation, and the enhanced ileal permeability suggests that the integrity of the gastrointestinal tract is compromised, which might facilitate bacterial translocation. PMID- 8511500 TI - Cholecystokinin in the regulation of gastric acid and endocrine pancreatic secretion in humans. AB - In this study, a selective antagonist of cholecystokinin (CCK)-A receptors, loxiglumide, was used to evaluate the role of CCK in the control of the release of gastrin and pancreatic hormones (insulin, glucagon, pancreatic polypeptide (PP), and somatostatin) after stimulation with exogenous CCK and ingestion of a standard liquid mixed meal in healthy humans. Exogenous CCK-8, which induced a small but significant increase in gastric acid secretion, resulted in dose dependent increments in plasma PP levels without significant changes in plasma levels of insulin, glucagon, or somatostatin. Pretreatment with loxiglumide resulted in a marked increase in CCK-induced gastric acid secretion and abolished the increments in plasma PP without alteration of plasma insulin, glucagon, or somatostatin levels. Ingestion of the liquid meal resulted in an immediate rise in intragastric pH from basal values of about 2 to pH6 lasting 90-120 min, and this was accompanied by significant increments in plasma gastrin, insulin, glucagon, PP, and somatostatin. Administration of loxiglumide (1200 mg orally) caused a reduction in the postprandial intragastric pH and the two- to three-fold increase in plasma gastrin. Plasma insulin and glucagon levels in tests with loxiglumide tended to increase, probably owing to accelerated gastric emptying, whereas plasma PP and somatostatin were significantly reduced. This study provides evidence that CCK exerts an inhibitory effect on gastric acid secretion and plasma gastrin release as well as a stimulatory influence on the release of PP and somatostatin via CCK-A receptors but does not influence directly insulin or glucagon secretion in man. PMID- 8511501 TI - No net splanchnic release of glutathione in man during N-acetylcysteine infusion. AB - Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N-acetylcysteine (NAC) in a high dose (150 mg/kg body weight primer plus 15 mg/(h x kg BW), corresponding to treatment of acetaminophen overdose, there was no change in the splanchnic glutathione efflux (95% confidence limits, -0.531 to 0.375 mumol/min). NAC increased hepatic plasma flow rate from 0.90 +/- 0.531 min-1 to 0.97 +/- 0.11 (mean +/- SEM; p < 0.05). The effects of NAC treatment on plasma amino acids corresponded to an increased load on hepatic metabolic N conversion and transamination among nonessential amino acids. Splanchnic uptake of serine, alanine, cystine, isoleucine, and phenylalanine increased after NAC compatible with stimulated hepatic glutathione synthesis. In contrast to the rat, plasma glutathione in man probably originates mainly from extrahepatic tissues. PMID- 8511502 TI - Effect of a somatostatin analogue (SMS 201-995) on antral gastrin cell hyperplasia and hypergastrinemia induced by a histamine H2-receptor antagonist. AB - The effect of a somatostatin analogue, SMS 201-995 (SMS), on antral gastrin cell hyperplasia (AGH) and hypergastrinemia associated with 14-day administration of the histamine H2-receptor antagonist (H2-RA) famotidine was studied in rats. When the famotidine group was compared with the control group, the antral gastrin cell (G-cell) number was significantly increased (P < 0.01) by approximately twofold, and the serum gastrin level was significantly increased (P < 0.01) by approximately sixfold. When the famotidine+SMS group was compared with the famotidine group, the G-cell number was significantly decreased (P < 0.01) by approximately 30%, and the serum gastrin level was significantly decreased (P < 0.01) by approximately 40%. These findings suggest that SMS may be useful for inhibiting AGH and hypergastrinemia induced by long-term H2-RA administration. PMID- 8511503 TI - Gastrointestinal symptoms in middle-aged diabetic patients. AB - Occurrence of gastrointestinal symptoms was investigated in a questionnaire-based survey of 89 randomly selected patients with insulin-dependent diabetes mellitus, 481 patients with noninsulin-dependent diabetes mellitus, and 635 nondiabetic control subjects. The prevalences of upper gastrointestinal symptoms, abdominal pain, diarrhea, and constipation were similar in diabetic patients and control subjects. Women with noninsulin-dependent diabetes mellitus had a significantly higher and women with insulin-dependent diabetes mellitus a significantly lower prevalence of gallstone disease than control women (29%, 5%, and 19%, respectively). We conclude that the occurrence and spectrum of gastrointestinal symptoms in middle-aged subjects with insulin- and noninsulin-dependent diabetes mellitus do not differ from those of the general population. PMID- 8511504 TI - Helicobacter pylori serology in patients with gastric carcinoma. AB - Helicobacter pylori-associated gastritis has been put forward as a distinct risk factor for gastric cancer. Furthermore, among H. pylori-positive individuals a correlation between a high serum level of H. pylori antibodies and the risk of gastric cancer has been found in two different studies. Other studies have challenged this hypothesis. We therefore studied the presence and level of H. pylori serum antibodies, using an enzyme-linked immunosorbent assay technique in 116 gastric cancer patients (65 men; mean age, 67 years; range, 23-92 years) and 116 controls matched for age and sex. Patients and controls were selected on referral for gastroscopy. The prevalence of infection in gastric cancer patients was 77% (89 of 116) and in controls 79% (92 of 116). This difference is not statistically significant, nor is the prevalence of infection in cases and controls of different age cohorts significantly different. High levels of serum antibodies were found in 46% (53 of 116) of gastric cancer patients and 40% (46 of 116) of controls. Comparison of the prevalence of high serum levels of antibodies for the total population and for the different age cohorts did not show significant differences either. We conclude that the comparison of actual H. pylori infection in a cross-sectional study of gastric cancer patients and controls does not enable relative risk calculation in the study of the role of H. pylori infection in gastric carcinogenesis. Prospective studies showing diminishment of the risk for gastric cancer after eradication of H. pylori are required. PMID- 8511505 TI - Prevention of duodenal ulcer recurrence with penicillin. A double-blind, placebo controlled trial. AB - Eradication of Helicobacter pylori is associated with a reduced recurrence of duodenal ulcer (DU). The relationship between H. pylori and DU has been interpreted as causal, but the evidence has been criticized for methodologic reasons. To ascertain whether an antibiotic with no effect on epithelial-cell integrity prevents DU recurrence, we conducted a randomized double-blind trial of phenoxymethylpenicillin (PEN), 2.4 twice daily, and placebo (PLA). Patients with an active DU and positive H. pylori culture from antral biopsy specimens were treated with 40 mg omeprazole daily for 4 weeks, but at week 2 they were allocated at random to PEN (85 patients) or PLA (85 patients) for up to 14 weeks. Those without recurrence during this treatment were followed up for another 6 months. Endoscopy and H. pylori culture were performed at the end of the treatment period and at the end of follow-up, and in between if ulcer symptoms recurred. During the treatment period the ulcer relapse rate was 5 of 58 (9%) in the PEN group and 34 of 68 (50%) in the PLA group (P < 0.0001, log-rank test), with 53% and 14%, respectively, of the patients in the two groups being H. pylori negative. The relapse rate in the PEN group did not differ between H. pylori negative and H. pylori-positive patients. The recurrence rate in the PEN group remained low for another 5 months but then approached the rate in the PLA group. The prevalence of H. pylori-negative patients at the end of follow-up was 20% in the PEN group and 10% in the PLA group. These data provide strong evidence that DU has a bacterial cause, with H. pylori as the likely agent. PMID- 8511506 TI - Gastric and pancreatic lipase levels during a test meal in dogs. AB - The levels of gastric and pancreatic lipases in the duodenum and the jejunum were measured during the digestion of a test meal in dogs. Using both a specific enzymatic titration and an enzyme-linked immunosorbent assay, it is shown for the first time that gastric lipase remains active in the duodenal and jejunal contents. An experimental device was set up for measuring the secretions and the intestinal flows of lipases during the digestion of a liquid test meal. In a dog equipped with gastric and duodenal cannulae, the secretion of gastric lipase was stimulated by food ingestion, reaching 3.0 +/- 0.3 mg/h (three times the basal secretion rate) during the 1st h of digestion. The total secretory outputs of gastric and pancreatic lipases recorded over a 3-h period of digestion were 7.2 +/- 1.2 mg and 18.7 +/- 1.2 mg, respectively. PMID- 8511507 TI - Human pancreatic proenzymes are activated at different rates in vitro. AB - The rates of activation of procolipase, prophospholipase (proPLA2), chymotrypsinogen, and trypsinogen were studied after incubation of human pancreatic juice with porcine enterokinase in vitro. Under the conditions chosen procolipase was fully activated within 10 min of incubation. Full activation of phospholipase (PLA2) was seen within 15 min, whereas complete activation of chymotrypsin and trypsin was not seen until after 30 to 60 min, respectively. The different proenzymes probably differ in their suitability as substrates for trypsin. A physiologic consequence of a differentiated activation of the pancreatic proenzymes in vivo could be a delayed proteolytic degradation of the lipolytic enzymes in the intestine. PMID- 8511508 TI - Piezoelectric shockwave lithotripters: differences in fragmentation efficiency in vitro. AB - In a comparative assessment of the stone fragmentation efficacy of different piezoelectric lithotripters 72 human gallstones consisting of 24 sets of 3 stones each were disintegrated in vitro using the Piezolith 2300, the EDAP LT.01, and the Therasonic. On the basis of the maximum diameter the calculi were divided into group A (6-15 mm; n = 3 x 16) and group B (16-25 mm; n = 3 x 8) and were treated by using the maximum energy setting of each lithotripter (Piezolith 2300: setting 4, high power; EDAP LT.01: 95%; Therasonic: setting 7). Shockwave application was terminated when the residual fragments measured < or = 4 mm or after a total number of 6000 pulses. With the Piezolith 2300 all calculi could be disintegrated into fragments < or = 4 mm. In contrast, fragmentation was not successful, even after 6000 applied pulses, in the case of 2 and 6 stones when using EDAP LT.01 and the Therasonic lithotripters, respectively. With the remaining concrements of group A (n = 3 x 11) the fragmentation end point was achieved after a lower number of pulses when the Piezolith 2300 (median, 250 pulses; range, 50-500 pulses) was used than with the EDAP LT.01 (1000; 150-2500; p < 0.01) and the Therasonic lithotripters (2750; 750-5500; p < 0.01). Similar results were obtained for group B (n = 3 x 6): the Piezolith 2300 required fewer pulses (200; 100-1250) than the EDAP LT.01 (1000; 500-1000; p < 0.05) and the Therasonic (2000, 500-4000; p < 0.05) units.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511509 TI - Capsular types and susceptibility to penicillin of pneumococci isolated from cerebrospinal fluid or blood in Denmark, 1983-1988. AB - By means of the capsular reaction test, we typed 2,294 pneumococcal strains isolated from blood or cerebrospinal fluid (CSF) in Denmark during 1983-88.91% of the strains belonged to types included in the 23-valent vaccine. Among 254 pneumococcal isolates from blood and CSF from Danish children, types 6A + 6B, 18C, 14, 7F, 1 and 19F, in that order of frequency, were the most common ones, accounting for 68%. Among 2,031 pneumococcal strains from adults, the most common isolates were types 1, 3, 14, 7F, 4, and 6A + 6B, accounting for 50% of all pneumococcal strains isolated from patients with invasive disease. Penicillin resistant invasive strains of Streptococcus pneumoniae are rare in Denmark (< 1%). PMID- 8511510 TI - Risk factors for hepatitis B virus infection in heterosexuals attending a venereal disease clinic in Copenhagen. AB - Markers of hepatitis B virus (HBV) infection were measured in 465 non-drug abusing heterosexually transmitted disease (STD) patients. HBV markers were found in altogether 70 persons, of whom 7 were HBsAg carriers. Those chronically infected were all born in HBV intermediate/high endemic areas. Gonorrhoea was the only STD that was correlated to an increased risk of HBV markers. Number of sexual partners, sex and age was not correlated with HBV infection, irrespective of country of origin. The risk of having HBV markers in an STD clientele in Copenhagen was highly dependent on the country of birth, as the prevalences were 7% (21/307) in persons born in Denmark, 19% (9/47) in those born in other low endemic areas and 36% (40/111) in those born in intermediate/high endemic areas. Falling incidence of gonorrhoea and other STD may render it difficult to point out risk factors indicative of HBV immunization in heterosexual STD patients. In low-risk countries, screening for HBV markers should however be offered to all immigrants and refugees as a part of an HBV immunization program. PMID- 8511511 TI - Assessment of clinical features predicting streptococcal pharyngitis. AB - A total of 133 patients who consulted 4 general practitioners in Bergen 1988/89 for sore throat were examined. 8 clinical parameters with expected predictive value for identifying streptococcal tonsillopharyngitis were recorded. Clinical examination was validated against bacteriologic examination at a microbiological laboratory. The prevalence of streptococcal infection (group A, C and G) was 29%. An algorithm was constructed which identifies 3 groups with varying probabilities of streptococcal infection. A positive predictive value of 62% in the group with highest prevalence and a negative predictive value of 90% in the group with lowest prevalence was found. The consequences of performing a confirmative test only on patients in the group with uncertain prediction for streptococcal disease was elaborated. Although slightly reduced accuracy was demonstrated, due to diminished sensitivity, selective testing is recommended. Another algorithm was constructed for use in situations where no confirmative testing is available. The positive predictive value in the group with highest probability of streptococcal infection was 51%, and the negative predictive value in the group with lowest probability was 84%. PMID- 8511512 TI - Helicobacter pylori in 205 consecutive endoscopy patients. AB - The presence of Helicobacter pylori in the gastric, antral mucosa of 205 consecutive, unselected gastroscopy patients was investigated by 1-3 biopsies for urea broth test and culture, 1 biopsy for histological examination and 1 blood sample for serology by ELISA. Overall, 41% were positive for H. pylori by culture, 32% by urea broth test, 24% by histological staining and 67%, 56% and 49% for the 3 cut-off limits applied to serology. Culture and serology indicated the presence of H. pylori in 79-92% of the 14 cases with duodenal ulcer, in 59 82% of the 28 cases with gastric ulcers, in 45-71% of the 51 cases with endoscopic gastritis and in 33-69% of 13 cases with oesophagitis. In patients with histological antritis, H. pylori was identified by culture in 71% (60/84), by serology in 95%, 88% and 81% with the different cut-off limits. The sensitivity of serology ranged from 99-78% depending on the cut-off limits and the specificity from 78-100% against all parameters combined. These results suggest that serology is a useful screening method for the presence of H. pylori. Future antibiotic treatment studies are required to evaluate the clinical relevance of H. pylori in gastrointestinal disease and to investigate the possibility to monitor eradication by serology. PMID- 8511513 TI - Occupational blood exposure among health care workers: I. Frequency and reporting. AB - The frequency and reporting rate concerning occupational blood exposure were investigated among former and currently employed medical staff at a Department of Infectious Diseases (DID) having a high prevalence of HIV-positive patients. Subjects were asked to complete an anonymous questionnaire describing occupational percutaneous exposure (PCE) and mucocutaneous exposure (MCE) to blood, experienced during their employment at the DID. 135 out of 168 (80%) subjects responded. 45 subjects described 37 incidents of PCE and 15 of MCE. 44 of the exposures (85%) involved HIV-positive blood and 6 (11.5%) involved blood from a patient with hepatitis B. Annual incidence rates of PCE and MCE were: for A) interns and residents, 0.51 PCE/year and 0.17 MCE/year; B) for senior residents and senior physicians, 0.13 PCE/year and 0.21 MCE/year; C) for registered nurses, 0.11 PCE/year and 0.03 MCE/year; D) for auxiliary nurses, 0.09 PCE/year and 0.11 MCE/year. 35% of PCE and 87% of MCE were not reported to the security representative, the major reason being that the subject felt it to be unnecessary. We conclude that medical employment, especially as interns and residents at clinics for infectious diseases, carries a real and serious risk of contracting infectious diseases due to occupational exposure to blood. The importance of reporting needs to be emphasized. PMID- 8511514 TI - Occupational blood exposure among health care workers: II. Exposure mechanisms and universal precautions. AB - We investigated mechanisms of mucocutaneous exposure (MCE) and percutaneous exposure (PCE) to blood, and compliance with protective barriers among all former and presently employed medical staff at a Danish Department of Infectious Diseases. All subjects were asked to complete an anonymous questionnaire. 135 out of 168 (80%) subjects responded. 37 incidents of PCE and 15 MCE were described. More than 50% of PCE had occurred without obvious explanation during medical procedures, or were caused by unexpected patient movement, while only 1 PCE was caused by recapping. 35% of PCE occurred during drawing of venous blood samples. Compliance with usage of gloves was high (70-100%), depending on the procedure, and 72% of the subjects claimed to have sufficient knowledge of the risk of blood exposure and how to prevent it. Yet 11 (73%) out of 15 MCE might have been prevented by appropriate use of protective barriers. To further reduce the frequency of blood exposure, the development of safer instruments and unceasing education in safer technique and use of protective barriers are of major importance. PMID- 8511515 TI - C-reactive protein in viral and bacterial respiratory infection in children. AB - C-reactive protein (CRP) was studied in 209 children treated in hospital due to middle or lower respiratory tract infection with serologically demonstrated viral or bacterial aetiology. Of the 110 patients with serological evidence of bacterial infection, either alone or in association with viral infection, 52% had CRP > 20 mg/l, 35% > 40 mg/l and 15% > 80 mg/l. Of the 99 patients with serological evidence of viral infection alone, 35% had CRP > 20 mg/l, but only 12% > 40 mg/l and 5% > 80 mg/l. Nearly all, 88%, of the 25 patients with CRP > 40 mg/l in association with viral infection had either an infectious focus, specific microbial or non-specific laboratory evidence suggestive of bacterial infection. By calculating diagnostic parameters at 3 cut-off levels of CRP, the level 40 mg/l seemed more useful than 20 mg/l or 80 mg/l for differentiation between viral and bacterial infections. By using a CRP value of 40 mg/l as a screening limit sensitivity was 0.55, specificity 0.88, positive predictive value 0.76, negative predictive value 0.55, and likelihood ratios of a positive and negative test result 2.9 and 0.74, respectively. It is concluded that low CRP values do not rule out bacterial aetiology of respiratory infection in children. On the other hand viral infection without bacterial involvement is very improbable if CRP is > 40 mg/l. Our results suggest that high CRP values rule out viral infection as a sole aetiology of infection; bacterial infection and antibiotic treatment should be considered in these cases. PMID- 8511516 TI - Infection of arterio-venous fistulas created for chronic haemodialysis. AB - One of the complications of chronic haemodialysis is infection at the venous access site. A retrospective chart review (1985-1990) was done on patients requiring venoaccess for haemodialysis. 197 patients had 254 arterio-venous (A-V) fistulas created. 40 patients had 71 prosthetic implants and 157 patients had 183 autogenous fistulas created. 16 (22%) prosthetic grafts were infected versus 8 (4.3%) autogenous fistulas (p < 0.0001). Bacteraemia was present in 9/16 (56%) infected prosthetic grafts and 4/8 (50%) infected autogenous fistulas. Seven (43.8%) of the prosthetic grafts required removal; 6 (37.5%) were cured with drainage, irrigation and antibiotics, and 3 (18.8%) with antibiotics alone. One (12.5%) of the autogenous fistulas was removed, 4 (50%) required revision and 3 (37.5%) were treated with antibiotics alone. Whenever possible, A-V fistulas should be created in the arms with an autogenous graft as infections are less and easier to treat. PMID- 8511517 TI - DNA amplification on cerebrospinal fluid for diagnosis of cerebral toxoplasmosis among HIV-positive patients with signs or symptoms of neurological disease. AB - Reactivation of Toxoplasma gondii can lead to a life-threatening intracerebral infection in immunocompromised HIV-positive patients. Due to the current diagnostic limitations for establishing an exact diagnosis of cerebral toxoplasmosis, a nested PCR system was developed for direct detection of T. gondii in cerebrospinal fluid. A storage temperature for samples of -20 degrees C and sample preparation using Proteinase K appeared to be critical for obtaining a high sensitivity of PCR. A total of 56 samples from 38 HIV-positive patients and 12 HIV-negative patients with symptoms or signs of neurological disease were evaluated by PCR. 5 of the 38 HIV-positive patients were diagnosed as having cerebral toxoplasmosis and PCR was positive in samples from all 5 patients. In the remaining 33, PCR was positive in one case and negative in 32. An exact etiological diagnosis other than cerebral toxoplasmosis was established in 5 patients. PCR performed on cerebrospinal fluid samples seems to be a fast, sensitive, specific and valuable tool for establishing the diagnosis of cerebral toxoplasmosis among HIV-positive patients at the time of presentation of symptoms or signs of neurological disease. PMID- 8511518 TI - Boosting effect of a second dose of measles vaccine given to 12-year-old children. AB - In Sweden, a two-dose programme of vaccination against measles, mumps and rubella (MMR) was introduced in 1982 and the target groups were children aged 18 months and 12 years. In 1993 the first age group of 12-year-olds that were vaccinated with MMR at 18 months will appear. The majority of the 12-year-old vaccines for many years, however, had already been vaccinated against measles and the MMR measles component was thus a booster dose. As the benefit of a booster dose against measles has been questioned, this was studied in a group of 163 12-year old children, 122 of whom had been vaccinated against measles as young children. Of the 41 unvaccinated children, 23 had a history of clinical measles. The mean neutralizing titre level of the earlier vaccinated children, prior to the booster, was lower than that of the naturally immune children (reciprocal titre level 8 versus 20). After the booster the corresponding titre levels were 13 and 23. Among the seronegative children receiving their first dose, this figure amounted to 14. A moderate rise in titre was seen in those with low prevaccination titres. As the antibody protection afforded by vaccination was slightly lower than that of natural infection, even after a booster, follow-up studies must be recommended to evaluate the long-term protection of both a single and a two-dose programme. PMID- 8511519 TI - Glucocorticoid receptors in mononuclear cells of patients with sepsis. AB - Glucocorticoid receptor (GR) hormone-binding activity was studied by a whole-cell method in mononuclear cells (MNC) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis. 4 patients were receiving dopamine, which did not affect the GR count. The patients' plasma cortisol concentrations were normal or slightly elevated. Despite a wide range, the mean GR count and affinity in MNC from septic patients did not differ from those in normal controls, suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis. PMID- 8511520 TI - Cyanobacteria-like body (CLB) in travellers with diarrhea. AB - The cyanobacteria-like body (CLB) is a recently described agent, causing a travellers' disease (TD) syndrome characterized mainly by diarrhea. It has been described in travellers who have visited Asia and Latin America. We report 6 cases seen over a 16-month period among those attending a travellers' clinic. All patients suffered from fatigue, watery diarrhea and abdominal cramps; some also lost weight. The episodes were recurrent. PMID- 8511521 TI - An unusual manifestation of Chlamydia pneumoniae infection: meningitis, hepatitis, iritis and atypical erythema nodosum. AB - A 37-year-old man was admitted to hospital with fever, muscle tenderness, headache and mild exanthema on the right thigh. During his hospital stay, the headache worsened and aseptic meningitis was diagnosed. A bilateral iritis developed, and the exanthema developed into an atypical erythema nodosum. In liver function tests, pathological results were recorded. Vasculitis was suspected but could not be confirmed. All serological tests proved negative except for a fourfold titre rise to Chlamydia pneumoniae. We concluded that the meningitis, hepatitis, iritis and atypical erythema nodosum were most probably due to a C. pneumoniae infection. PMID- 8511522 TI - Recurrent Pseudallescheria boydii sinusitis in acute leukemia. AB - Most episodes of fungal sinusitis in immunocompromised patients are caused by Aspergillus species. To treat such infections, surgical debridement and anti fungal therapy have been recommended; it is also clear however that an adequate neutrophil count is important in controlling such infections. We report a case in which fungal sinusitis was shown to be due to P. boydii and in which the infection recurred over a period of 2 years during episodes of neutropenia in spite of vigorous surgical and medical therapy. PMID- 8511523 TI - Treatment of echinococcus granulosus cysts. PMID- 8511524 TI - Transmission of hepatitis C via blood splash into conjunctiva. PMID- 8511525 TI - Serum factors and polymorphonuclear leukocytes in human host defence against Neisseria meningitidis. Studies of interactions with special reference to a chemiluminometric technique. AB - Luminol enhanced chemiluminescence (CL) was used to study the interactions of various serogroups of opsonized or nonopsonized meningococci (MC) with polymorphonuclear leukocytes (PMNL), and the results were compared with those of functional (serum bactericidal activity = SBA, phagocytic killing = PK) and nonfunctional (EIA and IFL) antibody tests. The inherent problems of inter-assay and day-to-day variations of the CL technique were solved by indexing the responses with the use of an international serogroup X reference MC strain (NCTC 10790). When opsonized with serum from healthy adults without a history of meningococcal (MC) disease, the pathogenic MC strains of serogroups A, B, C, Y (Orebro variant) and W-135 gave significantly lower CL indexes than the apathogenic ones of serogroups Y, Z, and 29E and of nongroupable strains (p < 0.001). The same patterns were obtained when the strains were opsonized with serum from Swedish children 1-3 years old and also with serum A Sudanese children. Higher levels of antibodies against MC serogroup A polysaccharide were found in sera from Sudanese children than in those of Swedish ones. Correspondingly, the CL indexes for MC of serogroup A were somewhat higher for the Sudanese children than for the Swedish ones. In spite of this an MC epidemic due to a serogroup A strain could not be avoided in Sudan, but could in Sweden, where the same strain was introduced, indicating that other factors than serum immunity are of importance for avoidance of an MC serogroup A epidemic. In various series of experiments it was shown that the CL technique, like the SBA and PK tests, can discriminate between functional and nonfunctional antibodies in healthy individuals, in patients during and after MC disease and before and after vaccination, whereas EIA and IFL tests cannot. It was also shown that in the presence of serum from healthy individuals without a history of MC disease, both the classical and alternative complement pathways are activated to kill or to induce phagocytosis of apathogenic MC, whereas only the classical pathway is activated for the pathogenic ones. In the presence of serum from an individual vaccinated with MC capsular polysaccharide vaccine (high levels of anti-MC capsular polysaccharide antibodies), the pathogenic MC activate both the classical and alternative complement pathways for induction of phagocytosis. It is concluded that the standardized CL indexing technique for pathogenic and apathogenic MC has several advantages over the laborious and cumbersome SBA and PK assays in demonstrating and measuring the presence of functional anti-MC antibodies. It also has the capacity to discriminate pathogenic from apathogenic MC, and under certain circumstances it might be used as a diagnostic tool. PMID- 8511526 TI - [Polymerase chain reaction in hepatitis C: increased sensitivity via amplification of shorter cDNA fragments]. AB - The aim of our study was to compare the sensitivity of hepatitis C virus polymerase chain reaction (HCV-PCR) by use of two different primer sets which amplify PCR products of different length. Serum samples of 70 patients with chronic hepatitis C were tested by "nested primer" PCR, using either "NCR primers" that amplify cDNA-fragments of 340 basepairs (bp), or by "PT primers" which amplify fragments of 59 bp only. HCV-RNA was detected in 40 patients (57%) by "NCR primers" and in 69 patients (90%) by "PT primers" (p < 0.001). 23 of 70 patients (33%), which were HCV-RNA negative by "NCR primers", were positive by "PT primers", but no patient negative by "PT primers" was found to be positive by "NCR primers". 20 healthy controls tested by both primer sets were all HCV-RNA negative. We conclude that the sensitivity of HCV-PCR is significantly improved by use of primers that amplify "short" PCR products and recommend the use of "PT primers" for HCV-PCR. PMID- 8511528 TI - [Stability of blood sedimentation rate following repeated mixing of the blood in a vacutainer tube (Seditainer)]. AB - The stability of the sedimentation rate (read at 1 hour) was tested after repetitive mixing of the blood in the same Vacutainer Sedimentation tube ("Seditainer", Becton-Dickinson). The results of 275 sedimentation probes were collected by the nursing staff during routine clinical work on 5 internal medical wards. Sequential sedimentation tests with the same tube after mixing the blood by 6 inversions for the first run and 10 inversions for the second run, or 10 inversions for the first run and 6 inversions for the second, gave identical results. This shows that 6 inversions provide sufficient mixing of the blood. Our definition of one inversion includes turning of the tube axis by 180 degrees plus turning back to the original (vertical) position. If only 3 inversions were performed, the results were less consistent with those after 6 inversions. In 38 of 623 sedimentation runs the readings were too late by 7.6 +/- 4.7 minutes. The corresponding sedimentation rates were 113 +/- 24% of the control values read in time. In 17 of the 275 probes (6.2%) it was the first sedimentation run which was read too late. This shows that repetitions of the sedimentation test may be necessary in routine clinical work. The study clearly demonstrates that repetition is possible with the original sedimentation probe, which provides a reliable result if the blood is remixed by 6 inversions. PMID- 8511527 TI - [Coronary angioplasty in octogenarians]. AB - Coronary balloon angioplasty was performed on 33 lesions during 28 procedures in 23 octogenarians (median age 83, range 80 to 87 years) between January 1989 and December 1991. 96% of the patients had grade III-IV angina pectoris. The median left ventricular ejection fraction was 64% (range: 38-85%). Single vessel coronary artery disease was present in 43% and multivessel coronary artery disease in 57%. Angioplasty was performed on 1 vessel in 85% of the procedures and on 2 vessels in 15%. Primary angiographic success was 97% for 33 attempted lesions with one failure to recanalize an old occlusion. One patient underwent emergency intracoronary stent implantation after failed angioplasty. None underwent emergency coronary bypass surgery. One patient (4%) had a myocardial infarction and 2 patients (7%) died during hospitalization, the first because of abrupt vessel closure during angioplasty, the second due to acute retroperitoneal bleeding on the 8th day post-angioplasty while fully anticoagulated for an intracoronary stent. Follow-up (median 17, range 8 to 39 months) was obtained for all patients. Out of the 21 patients with primary angioplastic success, 3 (14%) had died (1 cardiac and 2 non-cardiac). At 1 year actuarial survival was 86%, and survival free from myocardial infarction or coronary bypass surgery was 81%. Further angioplasty for either restenosis or another lesion was performed in 5 patients (24%). These results confirm that coronary angioplasty is an effective means of controlling anginal symptoms in a selected group of severely symptomatic octogenarians. However, when complications do occur they are linked to a significant mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511529 TI - [Spontaneous cerebrospinal fluid hypotension: value of cerebral MRI]. AB - Spontaneous intracranial hypotension is uncommon. Clinically it consists mainly of postural headache associated with CSF pressure lower than 5 cm H2O. Recently it has been reported that in this syndrome cerebral MRI shows diffuse and symmetrical meningeal enhancement increasing with Gadolinium and disappearing spontaneously without any particular treatment. We report the cases of two women in whom CSF pressure, several weeks after the appearance of headache, was in normal limits and whose cerebral MRI showed such meningeal enhancement. Meningeal biopsy in a search for chronic pachymeningitis was normal in both cases. Diagnosis was established afterwards in the light of recent publications. PMID- 8511530 TI - [How well do condoms protect against HIV infection?]. AB - A review of the literature shows that condoms offer good protection against HIV infection and other sexually transmitted diseases. A series of in vitro experiments demonstrate that quality condoms made of latex are impermeable to HIV. In addition, more than 30 in vivo studies confirm that condoms are highly effective in preventing the transmission of HIV. Condom breakage or slippage is relatively uncommon (1-5%). Most condom failure probably results from incorrect or inconsistent usage. Failures may be minimized by increasing experience, choice of quality condoms and by strictly following instructions for use. PMID- 8511531 TI - [Is Chinese medicine compatible with our way of thinking?]. PMID- 8511532 TI - [Ozone, respiratory function and bronchial reactivity. Study of a group of pre Alpine agricultural workers]. AB - Between April and October 1991, eleven farm workers from a Swiss mountain village (altitude 2800 feet) underwent a monthly check on lung function and bronchial responsiveness to methacholine at the end of a normal working day in the open air. The results were analyzed according to the ozone levels measured at a central station in the village and by passive ozone samplers worn by the participants the day of examination. The ozone levels measured at the central station varied between 31 and 109 micrograms/m3 (mean of the 8 hours before the examination) whereas the levels assessed by the passive samplers varied between 15 and 80 micrograms/m3. The lung function values and bronchial responsiveness were stable throughout the year, even in one asthmatic subject. There was no statistical correlation with the ozone levels measured at the central station or with the passive samplers, in spite of the fact that the subjects did strenuous outdoor work. The difference between the ozone values measured by the passive samplers and by the central station suggests that the individual exposure of the subjects was below the theoretical immission levels. PMID- 8511533 TI - [Heroin addicts in substitution programs]. AB - 40 heroin addicts of whom 20 were undergoing maintenance therapy with hydrocodone (Dicodid) and another 20 with methadone have been questioned by standardized interview regarding their previous history and present situation. With data on the history we examined how well heroin addicts succeed in getting away from criminality and prostitution and look for employment while undergoing drug maintenance therapy. We were also interested to learn whether reaching the aim depended on the maintenance medication, i.e. if hydrocodone is as appropriate as methadone for maintenance therapy. The inquiry showed a significant reduction of criminality and prostitution. The rate of employment was quite stable. The therapeutic successes, measured by employment, prostitution and criminality did not differ with medication by hydrocodone or methadone. Although the more reliable patients received hydrocodone and the less reliable methadone, they did not differ either in past history or in therapeutic success. We conclude that hydrocodone can be recommended for maintenance therapy of relatively reliable heroin addicts. PMID- 8511534 TI - [Superficial cerebral hemosiderosis: a rare cause of ataxia or hypoacusis]. AB - Superficial siderosis of the central nervous system (SSC) typically involves slowly progressive ataxia, hypoacusis and dementia, possibly with pyramidal signs and sphincter disturbances in combination with xanthochromic CSF with siderophages. However, there are also atypical oligosymptomatic forms. Before the era of magnetic resonance imaging (MRI), diagnosis was only possible at autopsy. Nowadays a firm diagnosis can be made during life by demonstrating the typical marginal hypointense signal in the T2-weighted images in the cerebrum, brain stem, cerebellum and spinal cord. Contrast-enhanced computed tomography may demonstrate widespread meningeal enhancement, but this sign is not specific for SSC. We present an oligosymptomatic case of SSC with slowly progressive ataxia and slight hypoacusis. The etiology, gross pathological and histopathological findings, differential diagnosis and therapy are discussed. PMID- 8511535 TI - [Preclinical resuscitation]. AB - Resuscitation outside the hospital setting is a topic of increasing interest and discussion. A satisfactory neurologic outcome after acute cardiac arrest depends on immediate basic and the advanced cardiac life support (BCLS + ACLS). To achieve better results in Switzerland it is necessary to promote resuscitation performed by the layman (BCLS) and improve the content and structure of emergency calls and prehospital first aid. Since a satisfactory neurologic outcome depends on an immediate start to basic resuscitation, general information and teaching to the public must be promoted. To secure rapid assistance there should be one single phone number (e.g. 144) for emergency calls throughout Switzerland. Professionalism in the workup of emergency calls and in first aid by specialized personnel produces good results not only in cardiac but also in trauma patients. PMID- 8511536 TI - [Transabdominal ultrasonography in pancreatic diseases]. AB - Transabdominal ultrasound renders complete imaging of the pancreas possible in 90% of cases. Ultrasound is very sensitive in diagnosing acute pancreatitis. Peripancreatic edema and fatty necrosis are both hypoechoic and cannot be differentiated by ultrasound but by dynamic computed tomography. Complications of pancreatitis and biliary obstruction in the case of biliary acute pancreatitis are well detectable. Focal dense parenchymal echoes and an irregularly dilated pancreatic duct are characteristic of chronic pancreatitis. Biliary and duodenal obstruction, portal vein thrombosis and pseudocysts as complications of chronic pancreatitis are clearly demonstrable by ultrasound. Pancreatic ductal carcinomas of more than 10 mm in diameter can be detected with a high degree of accuracy. Resectability can be judged reliably. PMID- 8511538 TI - [Therapeutic ultrasonography in case of chronic pancreatic cysts]. AB - Since 1975, it has become possible to drain cysts associated with chronic pancreatitis percutaneously under sonographic guidance. Thirty-seven cysts in 35 patients have been punctured by this method. After a 23-month follow-up, 24% of the patients were considered completely healed while 35% did not present with pain again. Failure of the treatment was observed in 41% of the patients (relapse ranging from 2 days to 10 months). We observed no mortality and a 14% morbidity rate. Repetition of puncture did improve the clinical result; this latter cannot be predicted by the existence or not of a communication with the ductal system. Large cysts located in the head of the pancreas and hemorrhagic cysts relapsed systematically and must be considered a contraindication for this treatment. By contrast, primary or secondary infection of the cystic content did not appear to be predictive failure factors. This method should be used, in a first approach, for small cysts in the head of the pancreas or for cysts in the body of the tail that do not bulge into the digestive tract. PMID- 8511537 TI - [Endoscopic ultrasonography--an addition to pancreas diagnosis?]. AB - Endoscopic ultrasonography (EUS) has been developed for high resolution imaging of the upper gastrointestinal tract and immediate surroundings, such as the pancreas and the biliary tract. The ultrasonic transducer at the tip of the instrument works with ultrasound frequencies of 7.5 MHz and provides delineation of small structures and lesions, but the ultrasonic penetration depth is not sufficient for visualization of organs such as liver, spleen and kidneys. In the diagnosis of pancreatic disease the advantages of EUS lie in the delineation of small endocrine and exocrine tumors of the pancreas, complementary to other procedures such as ultrasound, CT and ERCP. EUS is also the most accurate single diagnostic method in the local staging of pancreatic ampullary carcinoma, being superior to other modalities in the diagnosis of portal venous infiltration. The disadvantage of EUS is its poor ability to differentiate between malignant and focal inflammatory tumors of the pancreas. The role of EUS in the diagnosis of chronic pancreatitis has not yet been fully established. PMID- 8511539 TI - [Endoscopic therapy of biliary pancreatitis]. AB - Gallstones are the most important causes of acute pancreatitis. Endoscopic retrograde cholangiography (ERC) is indicated in all situations of acute pancreatitis where the cholestatic enzymes are elevated, the common bile duct is dilated or stones or sludge are detected in the gallbladder sonographically. Additional indications are cholecystectomized patients and where there is no evidence of heavy alcohol ingestion. If common bile duct stones are detected by ERC, endoscopic sphincterotomy is the treatment of choice. In severe cases of biliary pancreatitis in particular, endoscopic therapy improves the final outcome and reduces morbidity and mortality rates. The more severe the clinical situation, the earlier endoscopic therapy should be performed. PMID- 8511541 TI - Modern diagnostic evaluation and preoperative staging of esophageal cancer. AB - Esophageal carcinoma is a highly lethal disease with a dismal prognosis. Essential elements in the diagnosis of esophageal cancer are: a high index of suspicion; adequate knowledge of the precancerous conditions; optimal radiological examination; expert endoscopy with multiple biopsies and/or cytology; final staging including endoscopic ultrasonography, CT scan, MRI and, whenever appropriate, laryngo-bronchoscopy and ultrasonography with cytological puncture of cervical lymph nodes. This overview mainly concentrates on X-ray, endoscopy, endosonography and CT scanning. At present the routine use of MRI for preoperative staging cannot be recommended. PMID- 8511540 TI - [Precancerous conditions of the esophagus]. AB - In the upper aerodigestive tract, carcinogenesis in squamous cell mucosa is characterized by a tendency to field carcinogenesis leading to multicentricity of lesions and synchronous or metachronous multiple tumoral lesions, namely multifocality. During pretherapy broncho-esophagoscopy carried out on ENT-cancer patients, the rate of synchronous second primary cancer is 24%. In 85% of the cases, these second primaries are detected at an early stage (in situ, microinvasive or submucosal carcinoma) and do not give rise to symptoms. Early diagnosis of cancer of the upper aerodigestive tract is possible provided that high risk patients are recognized and screening endoscopy of the whole mucosa is performed in every high risk patient. On the other hand, squamous cell carcinoma and adenocarcinoma may occur with increased frequency in patients with esophageal lesions such as achalasia, caustic stenosis and Barrett's esophagus. The premalignant potential of these three entities is discussed. PMID- 8511542 TI - [Chemotherapy of esophageal carcinoma]. AB - In metastatic esophageal cancer, single agent or combination chemotherapy induces short remissions in only a minority of patients. Therefore, only selected patients should be treated. More than half of patients with locoregional disease will experience significant improvement through cisplatinum-based combination chemotherapy. However, this has so far not shown itself to influence overall survivaL. Combination chemo-radiotherapy is superior to radiotherapy alone in locoregional disease. Studies in operable esophageal cancer comparing chemo radiotherapy with surgery alone have not so far been reported. PMID- 8511543 TI - [IgA-antibodies against Helicobacter pylori in gastric secretions: gastric secretory immune response or salivary contamination?]. AB - IgA anti-HP concentrations in both gastric juice and saliva samples of 40 HP+ patients (15 f, 25 m) randomly referred for upper GI-endoscopy were measured. The presence of HP was investigated using histology (H&E and Giemsa stain), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA, F. Hoffmann-La Roche). IgA anti-HP in gastric juice and saliva was determined by ELISA; the same HP antigen was used as for serology (FPLC-purified native cell surface antigens including urease, free of cross-reacting flagellar proteins). The 40 HP+ patients were positive for HP by all three methods (except 4x CLO false neg, 1x serology false neg). A control group consisted of 12 patients (6 f, 6 m) with no HP detectable by each of the three methods used. No correlation was discernible between IgA anti-HP concentration in saliva and gastric juice of HP-positive patients (R = 0.05). In contrast, the correlation coefficient in HP-negative patients was R = 0.69 (p < 0.02). Great interindividual differences in specific IgA concentrations of both secretions were found. Surprisingly, in saliva and gastric juice IgA anti-HP was also detectable in some subjects negative for HP by all three tests applied. This finding remains to be elucidated but could represent ongoing local immune response in the absence of HP gastritis. In conclusion, saliva was found to contain IgA binding to HP-antigen. In HP-negative subjects contamination of gastric juice by saliva seems to be responsible when small concentrations of IgA anti-HP antibodies were detectable in gastric juice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511544 TI - [Strengths and weaknesses of endorectal ultrasonography]. AB - Endorectal ultrasound is the most reliable method in staging rectal cancer and is superior to computed tomography. In a prospective series of 152 consecutive patients, comparison of preoperative ultrasound staging and postoperative histopathological staging resulted in an overall accuracy of 90.1%. Overstaging was observed in 9.2%, understaging in 0.7%. Peritumoral inflammatory changes, preoperative radiotherapy and localization of the tumor in the lower rectum were the main reasons for overstaging. Understaging was seen in stenotic or only minimal invasive tumors. Accuracy in staging lymph nodes was 78.5%. Inflammatory changes in the nodes were responsible for either overstaging or understaging. Whether diagnosis will be improved with a higher frequency--mainly in lymph nodes -has yet to be proved. With knowledge of the reasons for misinterpretation, endorectal sonography is--mainly in the lower rectum--a valuable aid in evaluation of surgical procedure. PMID- 8511545 TI - [12 years of endoscopic stone removal]. AB - All 583 attempts at endoscopic clearance of biliary calculi, performed in the Gastrointestinal Unit, Inselspital Bern, were retrospectively analyzed from 1980 until 1991. The average age of the patients was 70; 56% were female and 44% male. In 1980, 26 ERCPs for bile duct stone removal were performed, whereas in 1991 the number had increased to 90. The substantial increase in 1991 occurred after introduction of laparoscopic cholecystectomy. Over the total period of 12 years all stones were removed endoscopically after papillotomy in 82%, while the success rate in 1991 was 90%. Morbidity was 5.4% and lethality 0.2%. Total morbidity did not change markedly. However, the number of severe complications requiring surgical repair was reduced from 1.7% between 1980 and 1986 to 0% between 1987 and 1991. These results suggest that endoscopic removal of bile duct stones is increasingly performed with high success and low complication rates. PMID- 8511546 TI - [Value of computerized tomography in acute diverticulitis of the left colon]. AB - This prospective study focuses on the prediction of late outcome after acute left colonic diverticulitis successfully treated conservatively and in which the diagnosis was confirmed radiologically (computed tomography [CT] and gastrografin enema [GE]). Acute diverticulitis was diagnosed in 226 patients. Sixty-six patients (29%) were operated on during their first hospitalization, and 2 of them died (3% mortality). The remaining 160 patients, successfully treated conservatively, had a CT and a GE within 72 hours of admission and entered this study. Signs of severity on CT included the presence of abscess(es) and/or extraluminal air and/or extraluminal hydrosoluble contrast (Gastrografin). Follow up averaged 25 months (range 1 month to 5.3 years). Twenty-seven of these 160 patients (17%) had a poor outcome (persistent diverticulitis in 12, colonic stenosis in 6, recurrences in 7, residual parasigmoid abscess and colovesical fistula in one each). When comparing these 27 patients with the 133 others it appeared that: (1) men up to 50 years of age were significantly more prone to develop such complications (p = 0.003); (2) the probability of developing a complication was significantly greater when the initial CT had revealed an abscess and/or extraluminal air and/or extraluminal Gastrografin (p = 0.005). These results support the view that elective colectomy can reasonably be proposed after a first attack of acute left diverticulitis treated conservatively in men up to 50 years of age, and/or in patients whose initial CT revealed findings of severe diverticulitis. PMID- 8511548 TI - [Annual meeting of the Swiss Society of Pediatrics. Neuchatel, 17-19 June 1993. Abstracts]. PMID- 8511547 TI - [Does laparoscopic lysis of adhesions make sense?]. AB - Between May 1989 and December 1991 23 patients were operated on laparoscopically for symptomatic peritoneal adhesions. 19 were followed up by telephone using a standardized questionnaire an average of 18.3 months post-operatively (range 5-36 months). 12 patients were totally painfree, 3 complained of slight pain, 2 patients of fairly severe and 2 of severe pain. 15 patients considered the outcome of the operation to be good or fairly good and 18 said they would undergo the same operation in similar circumstances. We therefore recommend laparoscopic adhesiolysis in cases of acute or chronic abdominal pain, provided other causes of abdominal discomfort have been ruled out. PMID- 8511549 TI - [The dental hygienist profession--quo vadis?]. PMID- 8511550 TI - [Extraction of the deciduous anterior teeth and its consequences in children with the nursing bottle syndrome]. AB - On eighty children, whose rampant carious and predominant periapical diseased deciduous maxillary incisors had been formerly extracted, the outcomes of the early extraction were inspected in regard to the later development of the permanent teeth and the general state of health. For 68 children gypsum models were analysed, whether the early loss of deciduous incisors had led to deficiency of place in the front of the upper jaw. The early tooth extraction and conservation therapy resulted in a clear improvement of children's physical condition and ameliorated the starting situation of permanent teeth to be preserved healthy. The earlier the milk-incisors had to been extracted the greater was the danger of a belated eruption of the permanent incisors. PMID- 8511551 TI - Epidemiology and risk factors of wedge-shaped defects in a Swiss population. AB - The purpose of this study was to determine the prevalence of wedge-shaped abrasion defects in the teeth of an adult Swiss population. 980 letters explaining the study were sent to randomly selected subjects. 391 persons (40%) belonging to two age groups (26-30 and 46-50 years) were checked for frequency and severity of wedge-shaped lesions on all buccal tooth surfaces. Furthermore patients were asked about dietary and prophylactic habits as well as other factors possibly relevant to this study. The frequency of severe wedge-shaped defects was 19.1% in the younger, and 47.2% in the older age group, with a mean of 3 affected teeth per person (pooled age group). On average, 34.8% of all patients suffered from tooth hypersensitivity. 84.6% of the examinees with wedge shaped defects complained of hypersensitivity at these sites. It is concluded that wedge-shaped defects cause considerable problems to more than one third of the population, and that such lesions are often combined with hypersensitivity of affected teeth. PMID- 8511552 TI - [An X-ray study of the incidence of asymptomatic hypertrophy of the coronoid process]. AB - Although the coronoid process is not part of the temporomandibular joint, hyperplasia of the coronoid process can effect the mandibular movement as the result of the impingement on the zygomatic arch which is demonstrated in the case of a 22-year-old man. In order to access the prevalence of the asymptomatic enlargement of the coronoid process we carried out an investigation on 2000 panoramic radiographs and found only one case of a 64-year-old man. The very rare coronoid process abnormalities demonstrated on routine plan films should best be demonstrated in computed tomography, appreciating the morphology and the deformity of the surrounding structures. PMID- 8511553 TI - [Computed tomographic imaging of the dentoalveolar-maxillary sinus lacuna of the dentate jaw]. AB - A human bone segment of the lateral maxilla was scanned using high-resolution computed tomography (CT) in contiguous parallel axis slices in order to image the topographical relationship between upper molars and the maxillary sinus. The bone segment was dissected analogously in 1 mm thick sections. After exposing contact films from these jaw cuttings, microsections were made for histological interpretation. The radiological-histological comparison between the CT-scans, contact films and the histologic specimens revealed absolute differences of 0.2 0.6 mm. The high resolution CT allowed an interpretation of details located between teeth and bone when the minimum bone thickness was 0.5 mm or more. First experiences with the CT-technique in orthodontic patients were promising, especially for the differential diagnosis of the dentoalveolar maxillary sinus relation. PMID- 8511554 TI - [Antibacterial chemotherapy. The use of antibiotics in dental practice--an assessment from the clinical viewpoint]. PMID- 8511555 TI - [The restoration of the anterior teeth. A structured collaboration between patient, clinician and the dental technician: a key element for the realization of esthetic rehabilitation--illustrated by clinical cases]. PMID- 8511556 TI - [If one takes a trip...]. PMID- 8511557 TI - [Adhesive systems for tooth-colored restorations. A review]. AB - The quality, longevity and the esthetic appearance of tooth-colored restorations are primarily dependent upon the integrity of the bond of the restoration with the enamel and dentin. Consequently, the enamel and dentin adhesives which are increasingly combined in the so-called adhesive systems play key roles in restorative dentistry. This paper describes the components, the clinical technique, the importance of the systems and the relevant adhesive mechanisms. PMID- 8511558 TI - Human cellular mixed stratified cementum: a tissue with alternating layers of acellular extrinsic- and cellular intrinsic fiber cementum. AB - Following the first description of the formal genesis of acellular extrinsic- and cellular intrinsic fiber cementum on growing human teeth, the present paper introduces cellular mixed stratified cementum as a particular tissue. Based on a large and diverse material (human premolars and molars) that was examined by various methods, such as microradiography, light microscopy using transmitted and polarized light, and scanning- and transmission-electron microscopy, the composition and structure of this type of cementum is described. Cellular mixed stratified cementum covers the apex, the apical third of the roots or more, and the furcational aspects of human teeth. With all methods employed, it was shown that this tissue consists in principle of acellular extrinsic- and cellular intrinsic fiber cementum, i.e. two major types of cementum that alternate or are in irregular sequences deposited upon one another. The dynamics of this layering and the fact, that, temporarily, root surfaces may remain unsupported by Sharpey's fibers as a consequence of this layering, are discussed. PMID- 8511559 TI - [The reproducibility of the manual checkbite in the wearers of complete dentures]. AB - Thirty-six new complete dentures were remounted by means of check bite records at the time of placement. The mandibular position was recorded three times in each patient by two clinicians using Bite Compound, a thermoplastic material, for the records. After individual transverse horizontal axis localization, the dentures were mounted in an articulator, and subsequently three-dimensional, electronic and computerized measurements were made with a special measuring instrument. In intraindividual comparison the reproducibility of the check bite records resulted in a mean value of 0.37 +/- 0.33 mm, whereby maximum deviations of up to 1.8 mm were observed. Repeated insertion of the maxillary dentures into the hardened impressions of the thermoplastic compound led to an error of 0.04 +/- 0.06 mm. The results of the two clinicians differed only slightly. PMID- 8511560 TI - [Implant-borne perioprosthetic suprastructures. The gerontological prosthetic implantological treatment concept with tapered crowns and shell-pin anchorages on Ha-Ti implants]. PMID- 8511561 TI - [The vertical jaw relation and complete dentures. The PRO-COR method: a procedure for the provisional mounting of casts in the articulator for simplified modelling of the wax rims. Provisional Camper Oriented Registration]. PMID- 8511562 TI - [Resin-bonded bridges. A review of alternative care for diastema]. PMID- 8511563 TI - [Defining a position in conservative dentistry. Of the withdrawal from mechanistic thinking or the end of the age of the amalgam]. PMID- 8511564 TI - [AIDS and business: who discovered it?]. PMID- 8511565 TI - ["The patient shouldn't get the impression he is under the hammer to the dental hygienist". Interview by Kurt Venner]. PMID- 8511566 TI - [The city of Bern: dental care for young people should not be struck out for all time. Interview by Kurt Venner]. PMID- 8511567 TI - [The setting up of a "Blood and AIDS" work group]. PMID- 8511568 TI - [Romania: dental care in a children's home]. PMID- 8511569 TI - [The HIV test in Switzerland 1992: incidence, pertinence, impact and quality]. PMID- 8511570 TI - ["Switzerland has a very advanced dentistry, of an excellent level". Interview by Kurt Venner]. PMID- 8511571 TI - ["The philosophy of a first-rate, personalized service. Interview by Catherine Strahm and Kurt Venner]. PMID- 8511572 TI - HIV and AIDS. PMID- 8511573 TI - HIV and AIDS. PMID- 8511574 TI - National Institutes of Health. Fraudbuster ends hunger strike. PMID- 8511575 TI - Evidence found for a possible 'aggression gene'. PMID- 8511576 TI - Molecular biology. New EMBL director reaches out to southern Europe. PMID- 8511577 TI - Where east meets west. PMID- 8511578 TI - Science held back by ghosts of the past. PMID- 8511579 TI - French government tries decentralizing excellence. PMID- 8511580 TI - Immunology powerhouse in the Marseilles hills. PMID- 8511581 TI - A lot more than a Nobel heritage. PMID- 8511582 TI - Supramolecular chemistry. PMID- 8511584 TI - Who are the Europeans? PMID- 8511583 TI - Nod factors and nodulation in plants. PMID- 8511585 TI - Natural selection at work on the surface of virus-infected cells. PMID- 8511586 TI - From RNA to DNA, why so many ribonucleotide reductases? AB - It is generally accepted that DNA appeared after RNA during the chemical evolution of life. To synthesize DNA, deoxyribonucleotides are required as building blocks. At present, these are formed from the corresponding ribonucleotides through the enzymatic action of ribonucleotide reductases. Three classes of enzymes are present in various organisms. There is little sequence similarity among the three classes of reductases. However, enzymic mechanisms and the allosteric behavior of the enzymes from various organisms are strongly conserved, suggesting that the enzymes might have evolved from a common ancestor, with the class III anaerobic Escherichia coli reductase as its closest relative. PMID- 8511587 TI - Interspecific and intraspecific horizontal transfer of Wolbachia in Drosophila. AB - Cytoplasmic incompatibility (CI) in Drosophila simulans is related to infection of the germ line by a rickettsial endosymbiont (genus Wolbachia). Wolbachia were transferred by microinjection of egg cytoplasm into uninfected eggs of both D. simulans and D. melanogaster to generate infected populations. Transinfected strains of D. melanogaster with lower densities of Wolbachia than the naturally infected D. simulans strain did not express high levels of CI. However, transinfected D. melanogaster egg cytoplasm, transferred back into D. simulans, generated infected populations that expressed CI at levels near those of the naturally infected strain. A transinfected D. melanogaster line selected for increased levels of CI expression also displayed increased symbiont densities. These data suggest that a threshold level of infection is required for normal expression of CI and that host factors help determine the density of the symbiont in the host. PMID- 8511589 TI - IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. AB - The biological functions of interleukin-6 (IL-6) are mediated through a signal transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. The IL-6-induced gp130 homodimer appears to be similar in function to the heterodimer formed between the leukemia inhibitory factor (LIF) receptor (LIFR) and gp130 in response to the LIF or ciliary neurotrophic factor (CNTF). Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal transducing molecules and activation of associated tyrosine kinases. PMID- 8511588 TI - Switch of CD8 T cells to noncytolytic CD8-CD4- cells that make TH2 cytokines and help B cells. AB - CD8+ T cells are a major defense against viral infections and intracellular parasites. Their production of interferon-gamma (IFN-gamma) and their cytolytic activity are key elements in the immune response to these pathogens. Mature mouse CD8+ T cells that were activated in the presence of interleukin-4 (IL-4) developed into a CD8-CD4- population that was not cytolytic and did not produce IFN-gamma. However, these CD8- cells produced large amounts of IL-4, IL-5, and IL 10 and helped activate resting B cells. Thus, CD8 effector functions are potentially diverse and could be exploited by infectious agents that switch off host protective cytolytic responses. PMID- 8511590 TI - Modal shifts in acetylcholine receptor channel gating confer subunit-dependent desensitization. AB - During the transition from embryonic to adult skeletal muscle, a decreased mean channel open time and accelerated desensitization of nicotinic acetylcholine (ACh) receptors result from the substitution of an epsilon subunit for gamma. A single ACh receptor channel of the embryonic type, expressed in Xenopus oocytes, interconverts between gating modes of short and long open time, whereas the adult receptor channel resides almost exclusively in the gating mode with short open time. Differences in the fraction of time spent in either gating mode account for the subunit dependence of both receptor open time and desensitization. Therefore, developmental changes in the kinetics of muscle ACh receptors may be imparted through subunit-dependent stabilization of intrinsic gating modes. PMID- 8511591 TI - Molecular cloning of an apolipoprotein B messenger RNA editing protein. AB - Mammalian apolipoprotein B (apo B) exists in two forms, each the product of a single gene. The shorter form, apo B48, arises by posttranscriptional RNA editing whereby cytidine deamination produces a UAA termination codon. A full-length complementary DNA clone encoding an apo B messenger RNA editing protein (REPR) was isolated from rat small intestine. The 229-residue protein contains consensus phosphorylation sites and leucine zipper domains. HepG2 cell extracts acquire editing activity when mixed with REPR from oocyte extracts. REPR is essential for apo B messenger RNA editing, and the isolation and characterization of REPR may lead to the identification of other eukaryotic RNA editing proteins. PMID- 8511592 TI - Rapid remodeling of axonal arbors in the visual cortex. AB - If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity. PMID- 8511593 TI - Chondroscopy: a new method for scoring chondropathy. AB - The purpose of this study was to evaluate the performance (simplicity, reproducibility, relevance) of chondroscopy as a method for evaluating cartilage damage. Chondroscopy consisted in endoscopic evaluation of the knee using a 2.7 mm Storz arthroscope under local anesthesia and recorded on videotape. Scoring of chondropathy was based on physician's overall assessment using a 100-mm-length visual analogue scale (VAS) and size and grade of cartilage lesions. Reproducibility was evaluated by variability (coefficient of variation [CV]) in the reading of chondroscopic evaluations of five patients five times by one physician and one time each by four different physicians. The correlations between scoring of chondropathy (VAS) and radiological articular joint space narrowing, demographic data (sex, age, weight), and disease characteristics (localization, etiology, activity) were studied in 84 outpatients fulfilling the American College of Rheumatology criteria for the diagnosis of osteoarthritis of the knee. The grade and size of the lesions were both correlated with the physician's overall assessment (r = 0.713 and r = 0.816, respectively). These two variables accounted for 72% of the variance of the VAS (multiple regression analysis). Intraobserver reproducibility was better than interobserver reproducibility (CV, 9% and 37%, respectively). There was a strong correlation between the scoring of chondropathy (VAS) and radiological joint space narrowing (r = .646, P < .0001). Moreover, in 17 of 33 patients without radiological joint space narrowing, VAS was > 20 mm. At variance, the body mass index was the single clinical variable found to correlate with the scoring of chondropathy (r = .282, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511594 TI - Erosive osteoarthritis. AB - Erosive osteoarthritis is a disorder that most often involves the hands of postmenopausal women. It can begin abruptly with pain, swelling, and tenderness. Distal interphalangeal joints are involved most frequently, followed by proximal interphalangeal joints. Occasionally there is metacarpophalangeal, carpal, or large joint involvement. The female-to-male ratio is approximately 12:1. There are no known HLA associations. Laboratory studies generally are negative. A mild elevation of the sedimentation rate may occur. Radiologically, the disorder is characterized by central erosions and the "gull wing" deformity. Synovial pathology has shown changes consistent with both rheumatoid arthritis and osteoarthritis and manifests the stage of disease at the time of biopsy. The etiology remains obscure, but hormonal influences, metabolic disorders, and autoimmunity have been implicated. Treatment is largely supportive with physical therapy, nonsteroidal antiinflammatory drugs, and occasionally prednisone. Overall prognosis is good, although deformity and impairment of hand function may occur. For this reason, a reassessment of treatment strategies may be in order. PMID- 8511595 TI - Fibronectin, cartilage, and osteoarthritis. AB - Fibronectin is a multifunctional glycoprotein present at low levels in the extracellular matrix of normal cartilage. In this tissue, as in others, it may be a component of a cell matrix adhesion complex together with cell-surface proteoglycans but also may play a role in the organization of the extracellular matrix. In osteoarthritis (OA), fibronectin content is markedly increased in the altered matrix because of an increased synthesis by the chondrocytes and accumulation in the extracellular matrix. At least part of the fibronectins synthesized in one degenerated cartilage is composed of isoforms more sensitive to proteolytic cleavage that are absent in normal cartilage. This increased content of fibronectin during osteoarthritic processes might entail several consequences related to the multiple functions of fibronectin and its generated fragments, namely a change in chondrocyte phenotype, a switch in synthesis of collagen type, an increased activity of locally secreted metalloproteases, and induction of self-proteolytic activities against gelatin and fibronectin. However, it is not yet clearly understood whether the early increased synthesis of fibronectin in OA acts as an "agent" in an attempt to repair cartilage by the chondrocytes or whether it acts as a deleterious "agent." PMID- 8511596 TI - The epidemiology of ankylosing spondylitis. AB - This review focuses on various epidemiological aspects of ankylosing spondylitis (AS). Diagnostic criteria currently available are described, and their use in scientific studies as opposed to everyday clinical practice is discussed. Present knowledge of the prevalence of AS is addressed in detail with particular emphasis on discrepancies caused by variations in population frequencies of HLA B27 and those caused by differences in study designs. PMID- 8511597 TI - Magnetic resonance imaging of the brain in neuropsychiatric systemic lupus erythematosus. AB - To determine the utility of magnetic resonance imaging (MRI) of the brain in diagnosing active neuropsychiatric disease in systemic lupus erythematosus (NP SLE), a prospective study of 51 hospitalized systemic lupus erythematosus (SLE) patients during 64 separate episodes of suspected NP-SLE was initiated. In addition to standard hematology, chemistry, and serological tests, the workup included MRI in all patients. A computed tomographic scan of the brain was obtained in patients enrolled in the first year of the study. Of the 64 neuropsychiatric episodes, 42 were attributable to NP-SLE and 22 were attributed to causes other than SLE. Neuropsychiatric complaints unrelated to lupus included depression (n = 6), seizures (n = 5), headache (n = 3), altered mental status (n = 2), aseptic meningitis (n = 2), cardiovascular accident (n = 2), transient ischemic attack (n = 1), and vertigo (n = 1). The MRI was abnormal in 34 of 64 (53%) episodes. MRI abnormalities were more common in patients with focal neurological deficits (19/26) than in those without focal findings (15/38; P = .008) and in patients with nephritis (19/24) than in those without renal disease (15/40; P = .002). MRI abnormalities were as frequent in NP-SLE (25/42) as in cases with non-NP-SLE-related causes (9/22). Periventricular increased signal (PIS) was a frequent MRI finding (10/64). Enlargement of the prepontine cistern, an MRI finding not previously described in NP-SLE, was seen (14/64). Both findings were associated with the presence of hypertension and lupus nephritis. PIS similar to that seen in our patients has been described in otherwise healthy elderly individuals with risk factors for stroke, suggesting that vascular abnormalities may be important in the etiology of these lesions. In conclusion, abnormalities in brain MRI occur frequently in NP-SLE, especially in patients with focal neurological deficits. However, the presence of similar MRI abnormalities in SLE patients with neuropsychiatric symptoms and findings with non-SLE-related causes limits the specificity of the MRI for diagnosing NP-SLE. PMID- 8511599 TI - Monoclonal antibodies in ovarian and prostate cancer. AB - Radioimmunoscintigraphy (RIS)--using radiolabeled monoclonal antibodies (MoAbs) to image disease--is a growing subspecialty of nuclear medicine. RIS of the reproductive tracts of men and women has shown encouraging results in imaging both primary lesions and metastases of these cancers. Ovarian cancer is the most fatal gynecologic cancer in the United States, and prostate cancer is the most prevalent form of cancer in men. Several MoAbs against reproductive tumor antigens were used with limited success in clinical trials before 1989. Most recently, MoAbs CYT-103 (satumomab pendetide) and OV-TL 3 have shown promise as safe, sensitive imaging tools for ovarian cancer. Although to date more agents have been used to image ovarian carcinoma than prostate cancer, research has been restimulated in prostate carcinoma imaging because of development of a promising MoAb conjugate, CYT-356. Radionuclide indium-111 appears to be the most promising radiolabeled to date for ovarian and prostate carcinoma RIS performed in the United States. In future clinical trials, consideration of safety issues and a standardization of methods among institutions using RIS are needed before the use of MoAb technology in cancer imaging will become routine. Comparative studies with more traditional methods like computed tomography are needed, as well as more trials comparing radioimmunoscintigraphic findings with pathological evidence. PMID- 8511598 TI - Lymphedema of the upper limb in patients with psoriatic arthritis. AB - Upper limb lymphedema occurs rarely in rheumatoid arthritis (RA) but has been reported only once in psoriatic arthritis (PsA). The pathogenesis is unknown. This study describes four patients (three women) with upper limb lymphedema, chronic symmetrical polyarthritis, and psoriasis. Three were seronegative, diagnosed PsA; one was seropositive. Age ranged from 39 to 64 years, duration of psoriasis was 6 to 42 years, and duration of arthritis was 6 to 12 years. Onset of lymphedema was unrelated to the extent or severity of arthritis, and no other cause for this condition was identified. Radiological appearances ranged from mildly abnormal to advanced joint destruction, but carpal disease was prominent in all patients. Lymphoscintigraphy was abnormal in three subjects. Lymphedema became bilateral in two and was associated with radiological progression of arthritis. Disease-modifying therapy produced improvement of lymphedema in two patients and correction of the lymphoscintigraphic abnormality in one. This study describes upper limb lymphedema in patients with PsA and suggests that local synovitis may play a role in its pathogenesis. PMID- 8511600 TI - Cardiovascular applications: current status of immunoscintigraphy in the detection of myocardial necrosis using antimyosin (R11D10) and deep venous thrombosis using antifibrin (T2G1s). AB - The remarkable progress in immunologic techniques in the development of monoclonal antibodies offers the potential for powerful new tools for the detection of cardiovascular disorders, such as acute myocardial necrosis and acute deep venous thrombosis, in an accurate, safe, and noninvasive manner. Historically the use of monoclonal antibodies has been viewed as a tool dominated by the field of oncology. However, because of the relative ease of identifying and characterizing well-defined, unique antigens on necrotic cells, blood clots, and cellular components of the circulatory system, the chance for success in developing a clinically useful diagnostic product is significantly enhanced. In addition to being unique, these antigenic sites are also virtually universal in their expression by the targeted tissues or cells in the human population. Also, the epitope for these antibodies is less prone to "shedding" than many of the tumor markers present on the surface of malignant cells. This review describes the clinical experience with two immunoscintigraphic diagnostic agents specifically designed for the assessment of cardiovascular disorders resulting in the death of myocytes and the formation of acute blood clots indium-111 antimyosin-Fab-diethylenetriamine pentaacetic acid for the detection of myocardial necrosis and technetium-99m antifibrin Fab' (T2G1s) for the detection of acute venous thrombosis. PMID- 8511601 TI - Radioimmunoconjugates in the detection of infection and inflammation. AB - Various nuclear medicine techniques are widely used to image foci of infection and inflammation. Among the relatively new radiopharmaceuticals for this purpose are radioimmunoconjugates such as labeled murine monoclonal antigranulocyte antibodies and labeled human polyclonal nonspecific immunoglobulin G. This article reviews some background information, mechanism of action, side effects, biodistribution, kinetics, results of clinical studies, and dosimetry of several radioimmunoconjugates both of murine monoclonal and human polyclonal origin. The efficacy of these agents has been demonstrated in a variety of clinical conditions. Radiolabeled immunoconjugates may emerge as convenient alternatives to the present technique of choice: in vitro blood cell labeling techniques with their inherent problems and risks. PMID- 8511602 TI - Current status of cancer immunodetection with radiolabeled human monoclonal antibodies. AB - The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy. PMID- 8511603 TI - Multiple matched ventilation-perfusion defects in illicit drug use. PMID- 8511604 TI - Cholescintigraphic normal gallbladder visualization with delayed or nonobservable bowel activity. PMID- 8511605 TI - Imaging of colorectal carcinoma with technetium-99m radiolabeled Fab' fragments. AB - In this phase III study, patients who had previously undergone surgery for colorectal cancer were studied using a technetium-99m (99mTc)-labeled anti CEA antibody (IMMU-4 [Immunomedics, Morris Plains, NJ] 1mg of protein) to evaluate recurrence. Total-body, planar, and single photon emission computed tomography (SPECT) images were performed within 6 hours of injection. Objectives were to evaluate the efficacy of the 99mTc-labeled anti-CEA antibody, to assess sensitivity and specificity of the agent in known lesions, and to detect occult disease. The impact of antibody study on subsequent surgery was also evaluated. The Fab' fragment has a molecular weight of 54,000 and is supplied as a lyophilized kit that can be instantaneously labeled with 20 to 30 mCi of [99mTc]pertechnetate. In 9 patients with known disease, planar spot imaging identified lesions in 7 (78% sensitivity), SPECT imaging detected lesions in 8 (88% sensitivity), and 1 patient did not have SPECT. In the group of 10 patients with occult (or equivocal) disease, planar imaging sensitivity was 50%, and SPECT sensitivity was 100%. Analysis by site showed 14 of 24 lesions detected by planar imaging (58% sensitivity), and SPECT detected 24 of 24 lesions (100% sensitivity). Tumors as small as .5 cm were visualized in the 19 patients studied. The surgeon judged the antibody study to be impact neutral in 73% of the cases and helpful in 27% of the cases when antibody study altered the presurgical plan. PMID- 8511606 TI - Clinical applications of indium-111-labeled monoclonal antibody imaging in colorectal cancer patients. AB - During the past two decades, the in vivo application of monoclonal antibodies (MoAbs) in cancer diagnosis and therapy have been widely studied. This can be related to three main factors: (1) dramatic improvement in monoclonal antibody production, revolutionized by Kohler and Milstein; (2) improvement in radioisotopes and monoclonal antibody conjugation procedure and further simplification and ease of use of these procedures; and (3) the apparent safety of single or, in selected cases, multiple administration of MoAbs to humans. The development of radioimmunoscintigraphy or radioimmunodetection has added a significant new dimension to nuclear imaging, and it is very likely to broaden our approach to diagnosis and perhaps therapy of malignant diseases. The indications and limitation of radioimmunoscintigraphy must be clearly outlined to the referring oncologists and surgeons. The unique capability of radiolabeled MoAbs in detecting occult disease, upstaging patients, and, most importantly, changing patient management must be emphasized. PMID- 8511607 TI - Geographical inequalities of mortality in developing countries. PMID- 8511608 TI - The geographical inequalities in mortality in Africa. AB - This paper reviews the progress that has been made in studies on geographic differentials of mortality in Africa. In general, there is very little known about adult mortality in many Third World countries, and the contributions of geographers have been limited in this area. In many African countries, enormous problems in studies on mortality were encountered due to incomplete and unreliable information. Differential levels of mortality are reported in different regions of the African continent and even within each country. Higher childhood mortality rates are recorded in West and Central Africa when compared with East and Southern Africa; relatively low rates are reported in the Magreb and the lowest in the small island territories. However, the role of geographic and environmental factors at both regional and urban levels are least exploited. Hence, many analyses of mortality in Africa have concentrated more on formal statistical materials and not on the realities of the existing ecological and environmental situation. The paper calls on geographers to exploit ways of utilizing the enormous clinic-based data in the continent. However, even more can be accomplished when geographers conduct interdisciplinary research on mortality in Africa. PMID- 8511609 TI - [Geographic inequalities in HIV infection and AIDS in sub-saharan Africa]. AB - The geography of HIV infection in Africa (which is the continent with the highest incidence rates) has varied features at each scale. The transmission is oriented preferentially according to axes and poles where the virus--because of local environmental factors--found favorable conditions to dissemination and spread. The dynamic of the epidemic results from factors related to sociologic, cultural, religious behaviour and to geographical, political and economic situations. The local combination of all the causal factors explains the complexity and diversity of the geographic characteristics of the African epidemic. The knowledge of the complexity and diversity of the geographic characteristics of the African epidemic. The knowledge of the causal factors calls upon various disciplines. Spatial networks, population movements and their consequences are analyzed. Geographical data together with sero-epidemiologic information initiate hypothesises related to the spatial dynamic of the epidemic and to the processes of regionalization. PMID- 8511610 TI - [Comparative evolution in mortality in North Africa from 1960 until today]. AB - In this paper, the evolution of mortality since 1960 has been reconstructed for Morocco, Algeria, Tunisia and Egypt. The procedure has been to collect in each country all the existing data (population register, surveys, etc.), to check chronological and spatial cohesion and to estimate reliability, before making a final choice of the best estimates. The mortality transition has started. On the whole, progress has been remarkable during the last 20 years. In 1970 life expectancy was only from 50 to 52 years in the region; today it reaches nearly 70 years in Tunisia, 66 years in Algeria and Morocco, and 64 years in Egypt. Infant mortality has decreased considerably. Differences with regard to child mortality increased between countries. Tunisia maintained first place with the lowest rates. Algerian rates, however, are decreasing and have approached those of Tunisia within the last 10 years. Morocco is still in an intermediate position, and Egypt lags behind. Infant mortality ranges from 55 per 1000 in Tunisia to 80 per 1000 in Egypt. Female overmortality was one of the important characteristics of the region in the years 1960 and 1970. There is a tendency towards a decrease and a concentration in the first years of life (between 1 month and 5 years). But it still exists, denoting a certain sexual discrimination. Progress in North Africa during the 1950s and 1960s has resulted in an intermediate position regarding mortality levels. PMID- 8511611 TI - Spatial distribution of mortality from leading notifiable diseases in Nigeria. AB - This study shows that a total of 36 notifiable diseases account for nearly all the reported deaths in Nigeria. When ranked by magnitude, measles, malaria, pneumonia, tetanus, dysentery and tuberculosis together account for 85% of all deaths. The objective of this paper is to gain an insight into the geographical distribution of deaths arising from these six leading diseases using the administrative states as the spatial framework. The data were obtained from the Statistical Unit of the Federal Ministry of Health and the emerging pattern of mortality is highlighted. An attempt is also made to identify factors that explain the observed variations among the states and the contiguous geographical regions in the country. PMID- 8511612 TI - The inequalities of morbidity and mortality in Mauritius--its ethnic [correction of ethic] and geographic dimension. AB - This overview of the changing patterns of morbidity and mortality on the one hand and ethnicity and geographic variables on the other is an attempt to understand the changes which are taking place in the economic and social geography of Mauritius. Recently in the economic literature, there has been constant reference to the changes taking place in Mauritius. This article explores the changing patterns of morbidity and mortality based on official censuses, reports and studies. It further seeks to relate these to the geography of Mauritius. PMID- 8511613 TI - [Geographic inequalities in mortality in Cameroon]. AB - Because of the geographic diversity of Cameroon, the analysis of spatial inequalities of mortality is a challenging research topic. This is true for mortality and morbidity as well as for the distribution of underlying factors. Among these are the geographic (or ecological) factors. The example of the distribution of infant mortality is given here. It seems difficult to isolate geographical and socioeconomic factors which are intertwined. Anyway, taking into account the spatial variation of mortality can be a fundamental element in the implementation of health policy. PMID- 8511614 TI - [Differences in mortality in the Dogon of Boni]. AB - Mortality has been analyzed at the level of a small population of approximately 5000 persons, part of the Dogon of Mali. They are separated into four distinct groups, each composed of from three to four villages. Adjusted life tables are estimated for two periods of five years: 1977-81 and 1982-86. First these tables were calculated for the entire population and then for two of the most densely populated massifs. Mortality is very high. However, it is different in the two areas. This difference, already notable in 1977-81, increased during the period 1982-86. Possible causal factors could be linked to the presence of primary health care in the Tabi region. Although very limited, the care changed elementary rules of hygiene. Moreover, comparison between villages point to the important role of the quality and quantity of available water in relation to child mortality levels. PMID- 8511615 TI - [Geography of mortality and birth in Pikine (Senegal): value and limitations of findings of the Civil State in African villages]. AB - Research conducted in Third World towns show the heterogeneity of health population status. Among the indicators, mortality and birth are the most frequent, but the quantity of data and the classical methods in demography make the localisation of high-risk population difficult. Civil Registration Data Base are seldom studied, especially by geographers. The author analyses the interest and limits of these data in a spatial perspective, i.e. mortality and birth rates, mortality and birth volumes, seasonal variations of mortality, and relations between seasonal variations and health system activities. The author's conclusion is on the necessity to include these indicators in the health information system after complementary research on possible bias. PMID- 8511616 TI - [Geographic inequality of death in South Asia, Southeast Asia and East Asia]. AB - The geography of mortality in South, Southeast and East Asia presents considerable disparities. The range is particularly large between Japan, where life expectancy is one of the highest in the world and Afghanistan or Cambodia, where it reaches only 40 years approximately. Male overmortality varies extensively from one country to another. Male undermortality still occurs in Bhutan (1.5 years); male overmortality reaches 6.4 years in the two Koreas. As elsewhere, the difference between male and female life expectancy increases with life spans. Various levels of development of the countries under consideration (examined through three variables: income per capita, urbanization and education) do not explain spatial inequality of mortality very well. In order to understand the disparities better, the macro-approach should be supplemented by a micro approach. PMID- 8511617 TI - The geographical inequalities of mortality in China. AB - The Chinese population accounts for one-fifth of the world's total, so any change in Chinese mortality will have a great influence on the change of the world population. Before 1949, Chinese population mortality was 25-33%, the high year was 40%, and infant mortality even reached over 250 per 1000 live births. After 1949, the mortality had a rapid decline: it was 20% in 1949, and 14-18% in 1950 1964. But in 1960, mortality went up to 25.43% because of the natural disasters. Since 1965 it has been under 10%. Chinese mortality was 6.58% in 1988. The lowest proportion was 4.95% in Heilongjiang Province. The highest was 7.13% in Yunnan Province. Urban mortality has always been lower than that of the countryside. The urban mortality was 7% in 1965, but it was not until 1978, that countryside mortality had just reached this level. It probably related to the economics, culture, environment, health care and etc. It is worth noting that urban mortality has increased in China since 1981. It was 6.44% in Shanghai in 1981, but it went up to 6.80% in 1988. This condition has been attributed to an aging population and environmental pollution. As family planning has been practised in China, it can be estimated that the Chinese population will be at its height in 2004, and will begin to decrease in 2005. PMID- 8511618 TI - Spatial patterns of mortality in Bangladesh. AB - This paper depicts the spatial patterns of mortality of the administrative upazilas of Bangladesh. Due to the absence of adequate data on mortality rates from across the country, the mortality rates of the upazilas are calculated from the age sex structure of the population of the respective upazilas employing the standardized mortality rates of divisional headquarters. Crude death rates are used to determine spatial patterns of mortality in Bangladesh. The patterns portray strong regional differences. Such differentiation is accounted for by traditional differences in demographic and socio-economic factors. Also, regression analysis is used to assist in explaining spatial variations. PMID- 8511619 TI - Regional inequalities of child mortality in peninsular Malaysia with special reference to the differentials between Perlis and Kuala Terengganu. AB - In Peninsular Malaysia child mortality rates (5q0) vary from 13 to 63 per thousand at district level. The spatial pattern is closely associated with the regional distribution of socio-economic factors. But due to multicollinearity it is difficult to isolate the influence of socio-economic variables from other variables by employing aggregated data. However, individual data collected in a case-control-study that was conducted in Perlis and Kuala Terengganu confirm the important role of socio-economic factors. So it should be possible to achieve a further reduction of child mortality by raising the income and educational level of the under-privileged groups. Apart from that, as the case of Perlis shows, the provision of family planning and preventive medical services may also contribute to lower child mortality independent from socio-economic changes. But, as the comparison with Kuala Terengganu shows, the utilization of family planning and preventive medical services is not only influenced by the accessibility to, but also by the socio-culturally determined acceptability of such services. PMID- 8511620 TI - The geo-systemic model and mortality in Ubon-Ratchathani. AB - The Thailand 'Rural Data Base' includes a number of variables in the social, economic, services, housing, agriculture and health fields. This data base comes from a survey at the village level. There are weaknesses in the data base- inaccuracies, missing data, etc ... that make it difficult to discover the structures that theoretically exist in the data using direct analysis methods, like correlation analysis for instance. The 2383 villages of the province of Ubon Ratchathani, in Thailand, are the units of this study. The objective is to uncover the hypothetical health disparities that exist among the villages and to devise a typology of villages that will show classes of villages that have significant problems and, also, classes of villages that could suggest concrete solutions and be used as models. Some variables of the data base are considered dependent (health indicators) and others are considered independent; they are used to build a model called 'geo-systemic' that is used to expose mortality differentials in Ubon-Ratchathani. PMID- 8511621 TI - [Geographic aspects of mortality in French Polynesia]. AB - The fast pace of social and economic changes which have occurred in French Polynesia over the last 30 years, have made this territory a choice ground for studying trends in mortality by revealing a fast and outstanding epidemiological transition. However, the breakdown of the population in small scattered human groups raises the statistical problem of measuring mortality. The crude mortality rate has decreased steadily from 17.5/1000 in 1945-1949 to 5.3/1000 over the last five years. However, the various infant mortality rate, in spite of their decline, is still exceeding those of Metropolitan France. The contrasted trends in the causes of mortality provides a means to classify French Polynesia in the group of small fast developing countries but still ranks it far behind its 'reference models' such as Metropolitan France or the developed countries in the South Pacific, Australia and New Zealand. Moreover, there are significant regional disparities which still exist between Tahiti and the outlying archipelagoes, mainly among causes of death. As a whole, distant islands remain significantly more affected by deaths resulting from infectious and parasitic diseases, in line with the model of epidemiological transition, where as the islands of Tahiti with 70% of the total population appears as a place of cumulation of infectious and degenerative diseases, in particular of overloading and cultural problems. The centre/periphery opposition between a metropolitan country and an overseas territory repeats itself at the local level between urban and rural environments. PMID- 8511622 TI - Geographical inequalities in mortality in Latin America. AB - This paper is an attempt to synthesize several models of health and levels of affluence in Latin America. An analysis is accomplished wherein various countries and regions of Latin America are classified for health purposes as either products of a poverty model or a wealth model. Variables utilized include: mortality rates in preschool children and infants; elderly mortality; life expectancy; and overall causes of death. All three of the general models can be found in different parts of Latin America. More developed countries and regions tend to approximate the wealth model where chronic and degenerative diseases dominate. Still, while life expectations are shorter in countries and regions with lower levels of development, some elderly are afflicted by chronic and degenerative diseases. PMID- 8511623 TI - [Regional and socioeconomic disparities in mortality in Latin America]. AB - Differences in life expectancy between various countries of Latin America decreased considerably between 1960 and 1979. More recently, this decrease has slowed down in the 1980s. Disparities between Latin American countries remain considerable. Indeed, some countries are near European standards, others are more similar to some countries of sub-Saharan Africa with low life expectancy. Statistical analysis has demonstrated that after 1960, disparities are associated with economic factors, life expectancy is lower than 64 years; with cultural factors life expectancy is higher. According to the results of a factoral analysis, it is possible to classify countries into six groups with regard to life expectancy. PMID- 8511624 TI - The problem of fuzzy cause-specific death rates in mortality context analysis: the case of Panama City. AB - In studies of mortality, small and fluctuating numbers of deaths are problems which are caused by infrequent reporting and small spatial unit reporting. To use Panama City as an example, the paper will introduce a Monte Carlo simulation which allows for the analysis of mortality even with small absolute numbers. In addition, Panama City will be used as an example where good medical care is available in every city district, so that social class differences between the districts have a negligible effect on most cause-specific death rates and infant mortality. PMID- 8511625 TI - Life expectancy and infant mortality in Latin America. AB - Life expectancy and infant mortality in Latin America vary extremely on the national level as for example from 20 per thousand and less in Cuba and Chile up to 100 per thousand and more in Haiti and Bolivia. The range of these rates is even greater considering the regional level within the countries. Case studies from Costa Rica and Chile do not only show the contrast between rural and urban areas, but also give an example how regional differences can be diminished in the course of a rapid mortality decline. The development of primary and secondary health care, especially when applied to rural and marginal urban population turned out to be the most important factor for this reduction. In Costa Rica 75% of the decrease of infant mortality can be attributed to these measures. In addition to reforms in the public health system improvements of sanitary conditions have been proven to be very efficient in the fight against infant mortality in Chile. But the level of mortality remains relatively high in those countries where endogenous factors of mortality decline have not been added to the exogenous ones to a great extent. A close connection between social stratification and level of mortality is quite evident in Brazil, where difficult living conditions in rural areas as well as in a big part of the cities prevent a reduction of mortality rates. PMID- 8511626 TI - Restructuring medical care: where are the sociologists? PMID- 8511627 TI - Community financing of health care in Africa: an evaluation of the Bamako initiative. AB - The Bamako Initiative, a controversial attempt to strengthen Primary Health Care using community financing and community participation and management was launched at a meeting of African Ministers of Health in 1987. This evaluation focuses particularly on the community financing aspects of the Initiative. Previous experiences of community financing highlight particular lessons for the development of the Initiative and issues likely to be encountered in implementation attempts. Four country case studies of the Initiative at its early stages of implementation (in June, July and August 1991) were conducted in Burundi, Guinea, Kenya, and Nigeria. Similar activities in Uganda were also studied. These were short studies of one month each and utilised methods of rapid evaluation. The studies aimed to direct implementers quickly to issues requiring attention rather than to reach overall conclusions regarding the success of the Initiative which would be premature at this stage. Price structures used by the Initiative need to consider the access of marginalised groups more than is the case at present. In addition, there is a need to ensure against over-prescription and commercialisation and to ensure that incentives for utilising most appropriate levels of care are maintained. The evidence suggests that most people do find amounts of money to pay for health services which are large in relation to their income. This is probably a tribute to extensive community support mechanisms. Nevertheless, it highlights the plight of those who fall through this safety net for whom even charges for very basic care may be prohibitive. On the other hand, it appears that in most cases, the Initiative's activities provide a service which is cheaper when all costs to the household are taken into account, than was available before. The quality of services included in the Initiative's activities in the five countries was highly variable. Success in raising substantial revenues has also been mixed. In some countries however, substantial funds have been generated and used to achieve real improvements in health services. Overall, the experiences of the five countries appear to have been highly dependent on a number of 'environmental' characteristics: a tradition or not of 'free' services; the adequacy of current resource availability and that immediately preceding the introduction of the Initiative; the existing stage and nature of decentralisation within the country; and the competition the Initiative's activities face with alternatives. PMID- 8511628 TI - User charges for health services in developing countries: a review of the economic literature. AB - Literature suggests that in theory, the efficiency of user charges for health services is related to the level of externality, the price elasticity of demand, the proportion of total costs which are private access costs, and the level of the government budget constraint. Theoretical models predict that price elasticity of demand for health services is likely to be higher for lower income groups and that user charges are therefore unlikely to promote equity, or reduce the discrepancies between the utilisation rates of the rich and poor, 'ceteris paribus'. Empirical evidence tends to confirm the latter prediction but to suggest that user charges in many countries provide the scope for welfare gains for the majority. Unfortunately, this scope is seldom exploited in practice. It is argued that many countries have little choice but to try to exploit the potential for majority gains, but that more emphasis should be placed on ensuring quality improvements than on superficial financial measures of success. PMID- 8511629 TI - Nutrition and the commercialization of agriculture: ten years later. AB - This paper reviews the results of studies examining the impacts of agricultural commercialization on food consumption and nutritional status carried out over the last 10 years. Several conclusions can be drawn. First, the income effects of shifts to cash cropping are highly dependent on pricing policy for cash crops. Short term gains seen in some schemes are often highly dependent on the maintenance of high prices for commercial crops. Second, those schemes in which subsistence production is protected or stabilized are more likely to show positive results with an increase in income generated from cash cropping. Third, increased income does not translate directly into increased food consumption at either the household or individual (child) level. Shifts in control of income from women to men are important. Fourth, morbidity, especially from diarrheal disease is an important predictor of child growth. A failure to improve morbidity of children may offset gains in food consumption and in some instances a decrease in the time women have to care for their children as a result of commercialization has resulted in greater morbidity among children. Finally, the question "Who benefits and who loses?" is rarely addressed in these studies. The impacts of commercialization are mixed. They are highly dependent on the nature of the crop, the control of production and income, the allocation of household labor, the maintenance of subsistence production, land tenure, and pricing policies for both cash crops and food stuffs. It is these 'intervening' factors, not crop choice, that appear to be the most crucial in the nutritional status of rural people. Economic, food and agricultural policies and programs that advantage the most vulnerable population groups are the most likely to provide positive benefits in terms of food security and nutritional status. To place the emphasis on commercialization per se is to misplace it. PMID- 8511630 TI - Housing, stress, and physical well-being: evidence from Thailand. AB - The proposition that poor housing and congested living conditions have a detrimental impact on health has been promulgated for at least 150 years. At a minimum, two major causal mechanisms are thought to be involved in the relationship between crowding and physical health. First, high levels of household crowding can produce stress that leads to illness. Second, through shared physical proximity, household congestion contributes to the spread of communicable disease. The outcomes can be exacerbated by poor quality housing. A significant body of research, conducted primarily in affluent countries, has documented the detrimental effects of housing conditions on a variety of illnesses, including various contagious diseases. Poor housing has even been linked to high infant and adult mortality rates. The view that poor housing conditions and household crowding inevitably leads to poor health is challenged, however, by several observers, who question the role played by both crowding and housing quality. Most existing research has been conducted in affluent countries. Little is known, however, about the nature of these relationships within the context of less developed countries, where health status and housing quality are generally much poorer and where levels of household crowding are generally higher. Determination of the effects, if any, of housing quality--including household crowding--on physical health in developing countries is particularly important given the rapid growth of their urban populations and the difficulty of increasing the physical infrastructure fast enough to keep pace with this growth. This paper reports on an investigation of the impact of housing conditions and household crowding in the context of one developing country, Thailand. Using data from a representative sample of households in Bangkok (N = 2017), our results provide reason for some skepticism regarding the influence on housing on health, at least in its objective dimensions. While the skepticism of some is based on a reading of the evidence in Western countries, we likewise find that, in Bangkok, objective indicators of housing quality and household crowding are little related to health. We do find, however, that subjective aspects of housing and of crowding, especially housing satisfaction and a felt lack of privacy, have detrimental effects on health. Furthermore, psychological distress is shown to have a potent influence on the physical health of Bangkokians. Our analyses suggest that all three factors have independent effects on health outcomes bearing on both men and women. PMID- 8511632 TI - Costs and resource utilization for the treatment of incomplete abortion in Kenya and Mexico. AB - In much of the developing world, sharp curettage (SC) is the most commonly used technique for treating incomplete abortion. The procedure is usually performed in a hospital setting where physicians and operating theatres are available; it often involves light to heavy sedation for pain control and an overnight hospital stay for patient recuperation and monitoring. This study examined the hypothesis that use of manual vacuum aspiration (MVA)--a variation of vacuum aspiration (VA) -would be less costly than SC and thus be advantageous to healthcare systems with limited resources. The purpose of the study was to identify and, where possible, to explain the factors that contributed to cost differences between MVA and SC for treatment of incomplete abortion. To achieve this objective, researchers observed patient management and documented resource use at hospital sites in Kenya and Mexico. The results of the study support the researchers' hypothesis that, in most cases, treatment with MVA required a shorter patient stay and fewer hospital resources than SC, as the two techniques were practiced at the various study sites. The policy decision to adopt MVA, supported by procurement of instruments and incorporation of training in its use, is the basic prerequisite to achieving reduced levels of resource use. The study results also suggest that the full advantages of MVA can be realized only if it is introduced in conjunction with certain changes in patient management, such as offering outpatient treatment for incomplete abortion. PMID- 8511631 TI - Stress and exercise among the Japanese elderly. AB - This study seeks to replicate and extend research on the stress process by examining the relationships among stress, social support, physical exercise, and depressive symptoms with data provided by a recent nationwide survey of older adults in Japan. The findings reveal that more frequent physical exercise is associated with less psychological distress. Moreover, the data suggest that some (but not all) types of stressors tend to diminish the frequency of physical activity. Finally, and perhaps most important, the results reveal that social support tends to promote more frequent exercise. This can occur in two ways. First, more emotional support was related to better exercise habits. In addition, negative interaction was also associated with more frequent exercise, suggesting that informal social sanctions can foster positive health behaviors. PMID- 8511633 TI - Border crossing for hospital care and its implications for the use of statewide data. AB - A major concern of researchers using state data sets for population-based analyses and market share studies in the health care sector is the potential bias caused by 'border crossing'--patients receiving care out of state. By using the Health Care Financing Administration (HCFA) discharge abstract files for 1987 and 1988, we found that 'border crossing' is not a serious problem for the two large states we examined. Only 4.4% of New York patients and 2.15% of California patients received care out of state. At the county and zip code level, 'border crossing' is more frequent but tends to be concentrated in areas adjacent to other states. Even excluding all zips with more than 10% of patients crossing the 'border' results in a small loss of patients (2.2% for New York and 1.0% for California). PMID- 8511634 TI - Covert suicide among elderly Japanese females: questioning unintentional drownings. AB - A hypothesis is generated that despite high reported rates, suicide among elderly Japanese females is substantially underestimated due to misclassification of drowning suicides (ICD-9 E954) as unintentional drownings (ICD-9 E910). Data are adapted from 1979-1981 age-, sex- and cause-specific mortality tabulations for Japan, the United States, Australia, France, New Zealand, Norway, Sweden and the United Kingdom. Between ages 55 and 74 years, unintentional drowning rates for males and females in Japan begin to diverge sharply from those of comparison countries. By ages 75 and older, the rate for Japanese females is 13.5 per 100,000, which exceeds comparison rates by 7- to 15-fold. Although drowning suicide rates in this population are also high, its ratio of drowning suicides to unintentional drownings declines precipitously beyond ages 35-44. Excess drowning suicide underestimation among Japanese females is suggested by the absence of a similar change among the males and evidence of both a lack of drowning witnesses and sex differentials in life expectancy, living arrangements and suicide methods. A preliminary test of the drowning suicide hypothesis is proposed which incorporates psychological autopsies. PMID- 8511636 TI - A retrospective analysis of the cost-effectiveness of dental sealants in a children's health center. AB - A retrospective patient record analysis was conducted to study the cost effectiveness of dental sealants placed under routine, unrestricted practice condition in a fluoridated community. The 26 dentists who provided care at the clinic over the period of the study used their own clinical judgement to determine sealant placement or alternative treatment. Dental services for 275 patients at a children's dental clinic for low-income families were evaluated. All children had at least 3 years between their first and last dental visit (mean = 5.8 years). A lifetable analysis was conducted to compare the probability of survival (restoration-free tooth years) and costs incurred to first molars of children who did not receive sealants, received any sealants, or received sealants on all first molars. Among the children with sealants, comparisons were also made between sealed and unsealed teeth in children who did and did not have a first molar restoration prior to sealant placement. Costs included the costs of sealants and restorative treatments for these teeth over time. Depending on the conditions under which sealants were placed, cost-savings or improving cost effectiveness with time were found. A strategy of identifying children with prior restorations and sealing the remaining molars showed cost-savings within 4-6 years. For other comparisons, incremental cost-effectiveness ratios became more favorable over time. PMID- 8511635 TI - Physician prescribing decisions: the effects of situational involvement and task complexity on information acquisition and decision making. AB - This research utilized conjoint analysis and an analysis of information acquisition to examine the effects of situational involvement and task complexity on physician's decision-making process. The predictive accuracy of the linear model in predicting drug choice across situations was also assessed. A contingency model for the selection of decision strategies was used as a framework in the study. A sample of forty-eight physicians was asked to indicate their preferences and choices for hypothetical anti-infective drugs. Situational involvement was manipulated by telling physicians in the experimental group via the written scenario to assume that his/her decision would be reviewed and evaluated by peers and (s)he would be asked to justify drug choice. Task complexity was manipulated by varying the number of drug alternatives in a choice set. Results of the study indicated that physicians shifted from using compensatory to noncompensatory decision-making processes when task complexity increased. The effect of situational involvement on the decision-making process was not supported. However, physicians in the two groups were found to differ in choice outcomes and the attention given to specific drug attribute information. Finally, the linear model was found to be robust in predicting drug choice across contexts. PMID- 8511637 TI - Tobit, fixed effects, and cohort analyses of the relationship between severity and duration of rheumatoid arthritis. AB - Three methodological problems are commonly faced by researchers investigating relationships between severity and duration of illness among patients with rheumatoid arthritis (RA). (1) Linear regression techniques yield biased estimates when measures of severity are continuous but range between and include limiting values such as 0 and 3. (2) Data from the same patient over time are typically pooled together with data from different patients at the same time and over time. Models are then used that do not account for the statistical problems that can result from pooling. (3) Persons with varying years of duration of disease are typically combined and analyzed without any special attention to cohort effects. Changes in severity over time for cohorts of patients with fewer than 10 years of duration may be different from changes in severity of patients with more than 20 years of duration from the onset of the disease. In this study, severity is measured by the 0-3 disability scale in the Stanford Health Assessment Questionnaire (HAQ). Duration is measured by self-report of the onset of symptoms by subjects. Popular techniques are borrowed from econometrics- Tobit, Fixed Effects, and dummy variables for Cohort Models--that were developed to address three analogous problems in economic data. The three economic techniques are applied separately and together using data collected by Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) on 330 RA patients in 1981 who were followed until 1989. Although the Tobit technique does not appear to be especially useful with these data, Fixed Effects and Cohort Models do appear to be useful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511639 TI - A critical appraisal of the demand/control model of the psychosocial work environment: epistemological, social, behavioral and class considerations. AB - During the last decade the demand/control model has emerged as the dominant model to explain the relationship between the psychosocial features of work organization and health. Although originating from the field of occupational social epidemiology, the conceptual and methodological basis of the demand/control model parallel construct based models used in social psychology. Using behavioral and sociological perspectives the current paper discusses the model's limitations. Recommendations regarding incorporation of social levels of analysis, the relationship between self-report and behavior, worker vs expert knowledge, and the generalized effects of stress on mental health are discussed to provide a positive heuristic to the demand/control model. PMID- 8511638 TI - Traditional birth attendants and maternal mortality in Ghana. AB - Maternal mortality is high in most African countries, particularly in rural areas where access to formal health care is limited. The sociopolitical and economic environment complicates the medical factors directly responsible for this high rate. Since the 1970s many African countries have addressed this problem by training traditional birth attendants (TBAs) in health promotion and in the basics of safe delivery and referral. The Danfa Rural Health Project in Ghana has trained and supervised TBAs since 1973. It is located relatively close to the health services of the capital city of Accra, providing an ideal environment for the practice of trained TBAs. Thirty-seven trained TBAs currently practice in the area. Most provide patient education and encourage women to go to the health center for preventive services. However, many report routinely performing the high risk deliveries that they have been taught to refer to higher level care and that when they do refer, their patients may not go. Reasons for referral refusal frequently cited by TBAs include financial limitation or lack of transportation and the patients fear of disrespectful or painful treatment from medical personnel. In the rural environment, the trained TBA's greatest contribution to lower maternal mortality rates may lie in the area of health promotion rather than disease intervention. PMID- 8511640 TI - Demographic variables in fetal and child mortality: Hmong in Thailand. AB - Conventional theories would not predict the 60% decline of infant mortality which has occurred among the Hmong population of Thailand, from 123/1000 in the mid 1960s to 48 in the mid-1980s. The Hmong population in northern Thailand has sustained high fertility and low use of modern health services. Most Hmong live in relatively remote rural villages and earn their living by self-employed farming. They have low levels of education, especially for women. They live in multi-generational patrilineal-patrilocal extended family households. Women's status is low. These characteristics contrast strongly with the majority ethnic Thai population, among whom a comparable mortality decline has been accompanied by widespread use of family planning, rapidly declining fertility, widespread use of modern health facilities, rapidly increasing levels of education for both sexes, rapid economic development, and a predominance of nuclear-based family households. Distributions of Hmong pregnancies by birth order and maternal age have remained relatively constant while fetal and young child death rates have declined for each level of parity and all maternal ages in recent cohorts. As predicted by conventional theories, infant mortality rates are highest among higher order births and for births to mothers of the highest ages, however there is relatively little effect on risk of infant mortality of first order pregnancies, or births to very young (10-14 year old) women. Fetal and infant mortality have declined steadily in recent cohorts at each parity level and all maternal ages. Modern medical care and decline in a surplus of female deaths associated with low status of women might explain the declines in fetal and child deaths regardless of parity or maternal age. Use of modern medical care for delivery is recent and accounts for less than 10% of all recent Hmong births, but survival rates are not consistently or significantly higher for children born with a modern birth attendant. Sex-specific mortality rates calculated from reproductive histories show no surplus of female deaths in the past, but females have benefitted more from recent mortality declines than males. Ethnographic evidence suggests that Hmong have customs which act to protect the health of mother and child ('chicken soup theory'), and that they are predisposed to accept innovations (including use of modern medicine) which they see as beneficial. This may allow them to respond especially quickly to small opportunities for improving their children's survival, as compared with other ethnic groups. PMID- 8511641 TI - Processing narratives of self-destructive behavior in routine medical encounters: health promotion, disease prevention, and the discourse of health care. AB - This study asked how patients and doctors process self-destructive behaviors that warrant preventive action, such as smoking, substance use, and sexual practices. Although many suggestions have appeared about how physicians should encourage health promotion and disease prevention by counseling patients about self destructive personal habits, few studies have examined actual encounters to assess how patients and doctors communicate about these matters, and prior research rarely has considered the social context of self-destructive habits. The present research has been influenced by a growing recognition of narratives, embedded in the sociocultural context of medical encounters, as an important analytic focus in the study of patient-doctor communication. Our conceptual work extended perspectives from literary criticism, critical theory, and narrative analysis in the humanities and social sciences to focus on elements of sociocultural context, ideology, social control, underlying structure, and superficially marginal features of discourse in medical encounters. Based on a critical review of both quantitative and qualitative techniques in research on patient-doctor communication, we developed an interpretive method with systematic criteria to guide the sampling of encounters, transcription of recordings, interpretation of transcripts, and presentation of findings. We applied the interpretive method to 50 encounters selected randomly from a stratified random sample of 336 audiotaped encounters involving patients and primary care internists. As shown by two illustrative encounters, the discourse of health care reinforces ideologic principles of professional surveillance and individual control in dealing with patients' self-destructive tendencies. Contextual issues remain largely marginal features of the discourse, despite their pertinence to the goal of prevention. Narrative analysis provides a useful method to study the processing of self-destructive behavior in medical encounters. Future studies should continue to assess the variability of discourse in dealing with self destructive behavior and should begin interventions to test the efficacy of differing discourse styles. Meaningful improvements in health-care discourse depend partly on difficult changes in the social context of medicine, including policies that address social conditions contributing to substance abuse and other forms of self-destructive behavior. PMID- 8511642 TI - Factors associated with health behaviour among mothers of lower socio-economic status: a British example. AB - The Health and Lifestyle Survey is the first survey in the U.K. to compare with the databases available in North America. For the first time detailed information on the health status, beliefs, attitudes and behaviour of a representative sample of the British population is available to compare with the findings drawn from smaller locally based samples. Here the focus is on the factors associated with the performance of more low-risk health behaviours among mothers of low socio economic status (social class IV and V), specifically on whether the findings from a South Wales survey could be generalised to the equivalent group in a national sample. The outcome measure used was the Health Practices Index, developed by the Alameda County Researchers. Seventeen factors were modelled, using multi-way analyses of variance, to produce a final set of statistically independent factors related to health behaviour. The most striking findings were the importance of the association between type of tenure and health behaviour in both the local and the national sample for this social class group; the lack of any association between education and health behaviour in the national sample; the failure, now well recognised, to find statistically independent associations between measures of attitudes/beliefs and health behaviour. Finally, the implications of the results are discussed in the light of recent and current trends in health education and promotion. PMID- 8511643 TI - Community participation in disease control. AB - The main determinants of community participation in disease control programmes are identified and a framework with eleven variables is developed. Attention is drawn to the political background, community characteristics, the managerial capacity of the provider and the epidemiology of the disease. The framework is designed to guide health professionals in the systematic assessment and monitoring of participation in disease control programmes. Analysis of the Ghanaian Guinea Worm Eradication Programme and the Nicaraguan Tuberculosis Control Programme are presented as case studies. They show that political support does not guarantee community participation in disease control programmes and stress the importance of other determinants such as commitment to PHC, intersectoral coordination, the project approach and human resources. The relevance of the epidemiology of the disease in determining what degree of community participation will be most effective is highlighted by the case studies. PMID- 8511644 TI - Communication between patients and physicians about terminal care: a survey in Japan. AB - We assessed patient-physician communication about terminal care in Japan by examining the accuracy of physicians' estimation of their patients' preferences as regards (1) information about diagnosis and prognosis, (2) the place of death and (3) the therapeutic strategy at terminal stage (life prolongation vs pain control). We conducted a questionnaire survey on inpatients (n = 201) in three hospitals; two in rural areas (Nagano and Okinawa) and one in an urban area (Tokyo). Simultaneously we asked physicians (n = 40) in charge of the patients to estimate their attitudes. The accuracy of physicians' estimation was assessed by correct estimation rate (CER) and kappa coefficient. (1) Approximately 80% of the patients preferred to have candid information about diagnosis and prognosis, regardless of the nature of their disease. The physicians were correct in estimation only in about half of the cases. About one sixth of the physicians' guesses were in opposite direction, while about one third failed to make any estimation at all. Thus, the overall CER was 42%, 57% and 62% in Nagano, Okinawa and Tokyo respectively. (2) While 70% of the patients wished to meet their death at home, the physicians estimated this fact correctly in less than half of the cases. The physicians frequently could not make any estimation (CER: 21%, 36% and 40% respectively). (3) Two thirds of the patients preferred pain control over life prolongation. Again, CER remained in the neighborhood of 50% (CER: 49%, 49% and 64% respectively). The analysis by kappa coefficients showed that the concordance between patients' preferences and physicians' estimation was not far from a figure expected by chance alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511645 TI - Social relationships of men at risk for AIDS. AB - Survey data collected in 1984-85 from a community sample of 637 gay and bisexual men were used to determine the features of social relationships that were most conductive to changes in both psychological health and AIDS-related sexual risk behavior. Multiple regression analyses showed that both the perceived availability of social support and the absence of conflicts in the social network were related to improve psychological health. At the same time, the subjective experience of integration into social networks was associated with increased psychological distress, and validation (the experience of being accepted by others) was related to a higher level of risk activity. These findings are discussed in terms of the social relationships among community members that share a common stressor--in this case the shared problem of being at risk for AIDS. PMID- 8511646 TI - Acculturation and symptoms: a comparative study of reported health symptoms in three Samoan communities. AB - A health questionnaire, which included a 91 item list of symptoms was administered to three groups of young Samoan adults. These young adults resided in a traditional Samoan village in Western Samoa (n = 50), several villages in modernizing American Samoa (n = 50) and in urban Honolulu, Hawaii (n = 52). Each yes response to a symptom was followed by an expanded interview providing details. The yes answer frequency and the contents of the expanded answers were examined with respect to site of residence. Western Samoan responses differed from the other sites in a number of areas suggesting possible differences related to the process of modernization. These response differences suggest four areas in which the stressors of modernization may have health influences: (1) wage employment outside of the family, (2) increased size of support networks by including non-family members and non-Samoans (3) the greater availability of alcohol, and (4) changes in the perceptions of food. PMID- 8511647 TI - Re-adjustment of Japanese returnee children from an overseas sojourn. AB - A questionnaire survey which was devised from the MMPI which was administered to Japanese children aged between 6 and 18 who had returned from an overseas sojourn for the duration of no less than one year (n = 1941) and matched control groups from the same schools who had no overseas experiences (n = 1354). Returnee children showed more dissatisfaction with their lives in Japan, but there was no indication that returnee children had more adjustment difficulties than their counterparts. In fact, they were less worried about their academic achievement and interpersonal relationships. Positive effects of the transcultural relocation were discussed as well as the adjustment. PMID- 8511648 TI - Highland-lowland contrasts in the impact of Old World diseases in early colonial Ecuador. AB - Old World epidemics played a major role in the demographic collapse of native peoples after 1492. In estimating aboriginal populations it is often assumed that once introduced Old World diseases spread unhindered and their impact was uniform. This paper indicates that there were often marked regional differences in impact of Old World diseases which were related not only to environmental conditions, but also to the size and character of native societies. Drawing on research on the demographic history of early colonial Ecuador, it demonstrates that there were marked regional differences in levels of depopulation, particularly between the highlands and lowlands. It argues that the presence of tropical fevers provides an inadequate explanation for the higher levels of depopulation in the lowlands and goes on to suggest that regional differences in the impact of Old World diseases were influenced by the size of Indian populations, their settlement patterns, forms of subsistence, social organization and ideology. These affected not only disease mortality, but also the ability of native groups to recover. PMID- 8511649 TI - Maternal mortality in rural and urban Zimbabwe: social and reproductive factors in an incident case-referent study. AB - A community-based incidence case-referent study was undertaken in a rural and an urban setting in Zimbabwe in order to define risk factors associated with maternal deaths at family, community, primary and referral health care levels. Referent subjects were drawn from place or area of delivery for each consecutive maternal death. Using a multiple source confidential reporting network for all maternal deaths, the maternal mortality rate for the rural setting was 168/100,000 live births and that for the urban setting was 85/100,000 live births. A model for interacting factors contributing to maternal mortality was designed. Haemorrhage and abortion sepsis were the major direct causes while malaria was the leading indirect cause in the rural setting. In the urban setting, eclampsia, abortion and puerperal sepsis were the leading causes of maternal deaths. It was found that all situations associated with diminished, or absent social support, that is, being single (Odds Ratio = 4.7, 95% CI = 2.2-9.8) divorced, widowed, one of several wives, cohabiting, or self-supporting carried an increased risk for maternal mortality, especially in the rural area. Income and level of education for index and referent subjects were comparable, probably because of the limited part of the population under study that belonged to a more affluent class. Distribution of cases and referents by religious-affiliation was also comparable. Age > 35 years and parity > 6 were significant risk factors for maternal mortality in the rural setting, whereas bad reproductive history with reported stillbirth or abortion constituted a high risk both in the city and in the rural areas (Odds Ratios 4-6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511651 TI - On behalf of the U.K. Nutritional Epidemiology Group. PMID- 8511650 TI - Maternal education and child survival: a comparative study of survey data from 17 countries. AB - A uniform analytical methodology was applied to survey data from 17 developing countries with the aim of addressing a series of questions regarding the positive statistical association between maternal education and the health and survival of children under age two. As has been observed previously, the education advantage in survival was less pronounced during than after the neonatal period. Strong but varying education effects on postneonatal risk, undernutrition during the 3-23 month period, and non-use of health services were shown--although a large part of these associations are the result of education's strong link to household economics. Differential use of basic health services, though closely tied to a mother's educational level, does little to explain the education advantage in child health and survival. However, the issue of the actual quality of services measured in the DHS is raised. Other issues concerning the roles of the pattern of family formation and differential physical access to health services are explored and discussed. PMID- 8511652 TI - Out of the closet: revolution and backlash. PMID- 8511653 TI - Reasonable efforts for children with disabilities: the parents' perspective. AB - This article reports the results of a content analysis of focus group interviews of parents of children with developmental disabilities, emotional disorders, and technology-supported needs. Perspectives regarding special needs, crisis situations, and parent-professional relationships are discussed. Implications for policy and practice include targeting specific services, monitoring values of programs and staff, and minimizing system-induced crisis. PMID- 8511654 TI - The social-environmental context of child clients: an empirical exploration. AB - This article examines the family and social-environmental problems reported by parents of 226 children seen at a child guidance clinic. Responses to a 21-item problem inventory revealed a relatively high frequency of family and social problems. Financial, school, employment, and housing problems were frequently reported, as were parental arguing and problems in dividing household chores. Problems varied by race and socioeconomic status. Low-income families reported more problems, both social and family, and were more likely to experience certain types of problems. White families reported a higher number of family problems and were more likely to report parent-child conflict, family violence, and health or medical problems. Regardless of income, African American families were more likely to experience problems with unsafe neighborhoods. PMID- 8511655 TI - Placing an infant for adoption: the experiences of young birthmothers. AB - This article describes the experiences of 215 young birthmothers who placed their infants for adoption through 30 maternity residences and agencies in 13 states. The prebirth services they received, their immediate postbirth experiences, and several characteristics of their adoption arrangements are described. A bivariate analysis revealed that several service-procedural variables are related to social psychological outcomes for the birthmothers at six months after the birth. Policy implications are presented. PMID- 8511656 TI - Military-induced family separation: a stress reduction intervention. AB - The Persian Gulf War focused public attention on the problems military families face in coping with military-induced family separation. This article highlights some of the unique stressors faced by active-duty, national guard, and reserve military families. Practice guidelines are presented to assist social workers in designing interventions to help these families. PMID- 8511657 TI - High-risk indicators for family involvement in social work in health care: a review of the literature. AB - Shifts in health concerns, fiscal restraints, technological advances, and demands for accountability have created severe tensions within health care settings. New demands point to the need for a redefinition of services. High-risk screening appears to be a clear method of delineating service need. A review of the empirical literature highlights individual, family, and illness variables that alone and together may improve identification of patients and families in need of social work services. The development of screening mechanisms may be a useful vehicle for improved psychosocial care and for the planning of social work services. PMID- 8511658 TI - Burnout in gerontological social work. AB - Although burnout in various fields of social work has been explored in some depth, there is a dearth of research on the gerontological social worker's experience with burnout. This article reports a national survey of burnout among 1,196 social workers who work with elderly people and who belong to either the National Association of Social Workers or the Gerontological Society of America. The extent to which these social workers experience the three components of burnout (emotional exhaustion, depersonalization, and personal accomplishment) is reported. The significant client, organizational, and personal factors associated with burnout among gerontological social workers are identified, and implications for social work practice are discussed. PMID- 8511659 TI - Preparing for sudden death: social work in the emergency room. PMID- 8511660 TI - The time-limited hot line. AB - Although long-term hot lines that focus on crisis intervention will undoubtedly dominate as an organizational model, time-limited approaches will be used with increasing frequency. The primary impetus behind their proliferation is the increasing visibility of the electronic media, particularly television, in investigating and reporting pressing health, mental health, and human services problems. As the mass media increasingly produces special reports, documentaries, and docudramas directed toward social problems and issues, local health and human services agencies will become increasingly motivated to provide a forum for public response. The time-limited issue- or problem-oriented hot line is the ideal vehicle for public response as well as for extending the human services network. This type of hot line also offers social workers a unique opportunity to share important mental health information through the media. PMID- 8511661 TI - Sexual abuse or Tourette syndrome? PMID- 8511662 TI - Predictors of temporal patterns of psychiatric distress during 10 years following the nuclear accident at Three Mile Island. AB - The present study examines psychiatric symptom levels during a 10-year period in a community sample of mothers of young children. All were identified in the early aftermath of the 1979 Three Mile Island nuclear accident, and followed through the accident's 1989 anniversary. Cluster analysis was used to identify long-term distress profiles during the study period; women's temporal profiles were found to be either (a) stable and at low, clinically nonsignificant levels of distress across all measurement points or (b) at consistently elevated, clinically significant levels that varied with the timing of postaccident events such as the restart of the undamaged reactor and the 10th anniversary. Subsequent multivariate analyses indicated that preaccident characteristics, as well as parameters reflecting respondents' initial involvement with, and reactions to the accident, were important for distinguishing between women within the two temporal profile groups. Implications of the results for both policy formulation and continued research on significant environmental stressors is discussed. PMID- 8511663 TI - Social class and mood disorders: clinical features. AB - We examined clinical features in 877 in- and outpatients affected by depression who were enrolled in psychopharmacological trials, subdivided according to Hollingshead's method into five social classes. The results showed that social class correlated significantly with the subtypes of mood disorders, with bipolar disorder being more frequent amongst the upper than the lower social classes. Furthermore, as already reported in other countries, social class appeared to influence the psychopathological pattern of depressive symptoms: somatization and anxiety were more frequent amongst the lower social classes, while psychic and cognitive symptoms were more common amongst the upper classes. PMID- 8511664 TI - The Dubai Community Psychiatric Survey: II. Development of the Socio-cultural Change Questionnaire. AB - The Dubai Community Psychiatric Survey was carried out to assess the effect of very rapid social change on the mental health of women in Dubai, one of the United Arab Emirates. In order to measure social change at an individual level, we developed a questionnaire covering behaviour and attitudes in a wide range of situations, the Socio-cultural Change Questionnaire (ScCQ). In this paper we give an account of the considerations that determined the form of the ScCQ, its structural characteristics, and its validity. PMID- 8511665 TI - Recent changes in the age- and gender-specific rates of attempted suicide in Gent. AB - The gender-specific rate of attempted suicide, calculated from hospital admission data, was significantly lower in 1990 than in 1986 in females and, when age is taken into account, in females younger than 35 and in males younger than 25 years. The incidence of suicide attempts seen by general practitioners also decreased. Indications for rejection of the artefact hypothesis as explanation for this decrease have been investigated. It was shown that the decrease in the prevalence was found at local and national levels and was not the result of a decrease in referrals to general hospitals. Moreover, the decrease in the rate was associated with an increase in the use of outpatient mental health facilities in females and with a trend to increase in the 15-24 age group. The number of suicide attempts referred by Community Mental Health Services to the general hospital and the suicide rate in out-patients remained constant during the study period. The findings do not support the artefact hypothesis but indicate that there was a real decrease in the rate of attempted suicide. Moreover, the findings suggest that out-patient treatment can be efficacious in the primary prevention of suicidal behaviour. PMID- 8511666 TI - Variation in requests to social services departments for assessment for compulsory psychiatric admission. AB - Eighty-two local authority social services departments in England and Wales participated in a postal survey of their responses to psychiatric emergencies, and 52 of the authorities provided detailed information on the rates of requests made to them for assessments under the Mental Health Act, 1983. This paper reports upon the variation in the rates of requests in different types of local authorities and regions. Variations are related to the availability of approved social workers (ASWs) and the Jarman Index of social deprivation. Requests for assessment and treatment order (Sections 2 and 3) are related to a greater number of ASWs, but only in county authorities, and requests for emergency admission (Section 4) are related to greater social deprivation, but only in London. Possible explanations for these findings are considered. Requests for the use of treatment orders have increased since the Act was introduced and now stand at more than one third of all requests, whereas requests for the use of emergency orders have declined to fewer than 8% of all requests. PMID- 8511667 TI - A systematic study of mental health services utilization by homeless men and women. AB - Psychiatric illness is overrepresented among the homeless, but mental health services are underutilized in this population in proportion to their needs. The current study was concerned with 900 homeless men and women randomly sampled and systematically interviewed with the Diagnostic Interview Schedule; it focuses on psychiatric and substance abuse rehabilitation service patterns and stated needs of this population in relation to specific psychiatric disorders. Although rates of lifetime treatment utilization were fairly high in comparison with general population utilization patterns, rates of treatment in the current year were low. In particular, outpatient services have been neglected for reliance upon inpatient services. Although the major reason cited for not obtaining treatment by homeless persons with mental illness was lack of insurance and inability to pay for it, having health insurance was not associated with mental health services utilization, nor were other important predictors apparent. Mental health professionals serving mentally ill homeless populations would best serve them by focusing on creative and innovative ways to improve the availability and attractiveness of ambulatory care services. PMID- 8511668 TI - Differences between long-stay and short-stay inpatients and estimation of length of stay. A prospective study. AB - To find possible differences between new long-stay inpatients and patients with shorter lengths of stay, a prospective study of 340 inpatients in the 4th week of hospitalization was carried out. The new long-stay patients differed from the others in diagnoses, symptoms, duration of prior hospitalizations, and socio demographic data. On the basis of the data assessed in the 4th week of hospitalization, we tried not only to predict future new long-stay patients, but also to estimate the length of stay for all 340 patients. A time-function model was employed with length of stay as a continuous variable, and this resulted in correct allocation to the quartiles in 38-48% of the cases. Six variables proved to be important for estimating length of stay: emotional withdrawal, blunted affect, mannerisms, duration of previous hospitalizations, living conditions (prior to admission), and marital status. PMID- 8511669 TI - The lifetime prevalence of psychosexual dysfunction among 55 to 57-year-olds in Iceland. AB - In this study, the largest Nordic study of its kind, investigated psychosexual dysfunction among subjects aged 55-57 years. The cohort included 862 subjects of both sexes and all were interviewed using the Diagnostic Interview Schedule (DIS). Results showed that 122 subjects had a lifetime diagnosis of psychosexual dysfunction. The lifetime prevalence of psychosexual dysfunction was 14.4%; of inhibited sexual desire, 9.8%; of inhibited sexual excitement, 3.5%; of inhibited orgasm, 2.1%; and of functional dyspareunia, 1.3%. Of the subjects with psychosexual dysfunction, 73% were women. The frequency was highest in those who had never married. Separated subjects had rates intermediate between the married and the never-married. The majority (76%) of affected subjects had only one dysfunction. However, 57% of them had received another psychiatric diagnosis at some time. Subjects with psychosexual dysfunction were less frequently diagnosed as suffering from alcohol abuse and dependence and social phobia than subjects with no psychosexual dysfunction. PMID- 8511670 TI - Direct DNA injection into mouse tongue muscle for analysis of promoter function in vivo. AB - The striated muscle of the tongue provides a readily accessible site for the introduction of DNA expression vectors. Parameters were established to use the striated muscle of the tongue as a model system for the examination of gene expression following the direct injection of DNA constructs bearing gene promoter sequences controlling the expression of reporter genes. Plasmid expression vectors were used that contained either constitutive or muscle-specific promoters directing the transcription of reporter genes. Chloramphenicol acetyltransferase (CAT), luciferase, and beta-galactosidase (lacZ) were used as the reporter genes to detect the promoter-specific expression of the injected DNA. The expression of the injected plasmids was directly correlated with the mass of injected DNA and the time of incubation following the injection. Maximal levels of reporter gene expression were observed seven days after the injection, and the expression was maintained for more than two months following injection. Simultaneous injection of two individual expression vectors bearing either CAT or luciferase reporter genes resulted in a dose-dependent level of expression for each of the plasmids. The linearity of the coexpression provided a means to normalize DNA uptake and analyze promoter efficiency. The troponin C-fast enhancer linked to its own promoter directed significantly more CAT expression than an enhancerless SV40 promoter-CAT plasmid, demonstrating that different promoter strengths could be determined in the mouse tongue muscle in vivo. This model system represents a convenient means to approach the functional analysis of muscle gene promoters in vivo. PMID- 8511671 TI - Paroxysmal nocturnal hemoglobinuria: correction of abnormal phenotype by somatic cell hybridization. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disorder thought to result from a somatic mutation in a hemopoietic stem cell. PNH may evolve to aplastic anemia or to acute leukemia. PNH cells are deficient in proteins attached to the cell membrane via a glycosylphosphatidylinositol structure, called the GPI anchor, and the primary lesion in PNH is thought to be a defect in the biosynthesis of the GPI anchor. We have recently established permanent lymphoblastoid cell lines that have the PNH phenotype and we report now the isolation of human-human somatic cell hybrid clones obtained by fusing them with normal lymphoblastoid cells. In all of 21 hybrid clones, obtained from five different patients, the expression of three different GPI-linked proteins on the hybrid cells was normal. These findings indicate that the PNH mutant gene is recessive with respect to the normal allele and that a recessive mutation can cause a clonal preneoplastic disorder. PMID- 8511672 TI - An insertion-deletion event in murine immunoglobulin kappa gene resembles mutations at heavy-chain disease loci. AB - The analysis of spontaneous somatic mutants gives insights into the regulation of gene expression. Human heavy-chain disease (HCD) is a monoclonal lymphoproliferative disorder characterized by the presence of truncated immunoglobulin (Ig) heavy chains without associated light chains. To better understand the molecular mechanisms leading to the loss of light-chain production, we have examined a murine cell line model of heavy-chain disease. R15, a spontaneous mutant of the IgA, kappa-producing myeloma cell line W3129, produces heavy chain but no light chain. The variant delta 15 derived from R15 resembles human HCD in that it secretes a shortened heavy chain with no associated light chain. Cloning and analysis of the R15 kappa light-chain gene revealed that a 358-nucleotide insertion of unknown origin replaced 22 bases of the wild-type leader-variable region (L-V) intron (IVS). Although this genomic change left the light-chain exons and known regulatory elements intact, it altered the mRNA processing pathway, yielding two alternative RNA products, neither of which encodes a functional protein. This mutant therefore provides new insights into how genomic changes can influence gene expression. PMID- 8511673 TI - New vector for transfer of yeast artificial chromosomes to mammalian cells. AB - A modification vector has been constructed to facilitate the transfer of yeast artificial chromosomes (YACs) to mammalian cells in culture by targeting a dominant selectable marker (G418 resistance) to the right arm of pYAC4 clones. The ADE2 gene is used for yeast selection with consequent disruption of the URA3 gene, allowing direct modification of YACs within the common host strain AB1380, and providing a simple test for correct targeting. This vector has been tested by modification of a 550-kb YAC containing part of the human MHC class II region and transfer to CHO cells by protoplast fusion. Analysis of 15 independent G418 resistant CHO lines obtained following fusion suggests the majority contain a complete YAC with moderate amplification in some lines. PMID- 8511674 TI - Introduction of YACs containing a putative mammalian replication origin into mammalian cells can generate structures that replicate autonomously. AB - Yeast artificial chromosomes (YACs) containing or lacking a biochemically defined DNA replication origin were transferred from yeast to mammalian cells in order to determine whether origin-dependent autonomous replication would occur. A specialized YAC vector was designed to enable selection for YACs in mammalian cells and for monitoring YAC abundance in individual mammalian cells. All of eight clones made with linear and circularized YACs lacking the origin and seven of nine clones made with linear and circularized YACs containing the origin region contained single copies of the transfected YAC, along with various amounts of yeast DNA, integrated into single but different chromosomal sites. By contrast, two transformants derived from circularized YACs containing the putative replication origin showed very heterogeneous YAC copy number and numerous integration sites when analyzed after many generations of in vitro propagation. Analysis of both clones at an early time after fusion revealed variously sized extrachromosomal YAC/yeast structures reminiscent of the extrachromosomal elements found in some cells harboring amplified genes. The data are consistent with the interpretation that YACs containing a biochemically defined origin of replication can initially replicate autonomously, followed by integration into multiple chromosomal locations, as has been reported to occur in many examples of gene amplification in mammalian cells. PMID- 8511675 TI - Expression of catalytic domains of human UMP synthase in uridine auxotrophic bacteria. AB - Orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC), which catalyze the last two steps in de novo UMP biosynthesis, are two distinct monofunctional proteins in bacteria and lower eukaryotes. In mammals, OPRT and ODC activities are contained in a single bifunctional protein labeled UMP synthase. The human UMP synthase cDNA was separated into the predicted OPRT and ODC domains using polymerase chain reaction techniques and the domains inserted into pUC19 expression vectors. Following transformation into OPRT- and ODC-deficient E. coli, the strains were able to grow on minimal media without uridine. The ODC-transformed bacteria expressed up to 24 times the level of activity found in a wild-type E. coli line. The OPRT transformed E. coli contained only 4-9% of wild-type activity. Western blot analysis with antiserum to human UMP synthase demonstrates that OPRT and ODC domains are being produced in the deficient cells by the respective vectors. The level of the domain protein approximates the level of enzyme activity. The complementation of the OPRT and ODC activities in the transformed deficient E. coli strains demonstrates that human UMP synthase can be separated into active monofunctional domains that will function in the bacterial cell environment. PMID- 8511677 TI - Continuing medical education in obstetrics and gynaecology. PMID- 8511676 TI - Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10. AB - Lamins A and C are products of alternate splicing of one transcript from a single gene. We have isolated a partial cDNA, cE1-2, whose 800-bp sequence is 99% identical to the 3' untranslated region of the lamin A/C gene. We report here the mapping of this gene and a closely related sequence to human chromosomes 1 and 10, more specifically, to 1q12.1-q23. The localization of cE1-2 hybridizing sequences to two different chromosomes suggests that one of these loci represents an as yet unknown member of the lamin gene family, either a pseudogene or an expressed gene. PMID- 8511678 TI - The present and future of obstetrics and gynaecology in South Africa. PMID- 8511679 TI - Implications of bacterial resistance for the use of beta-lactam agents in clinical practice. PMID- 8511680 TI - Alcohol and brain damage. PMID- 8511681 TI - Hypertensive crisis--the South African perspective. PMID- 8511682 TI - Helicobacter pylori prevalence in non-ulcer dyspepsia--ethnic and socio-economic differences. AB - Helicobacter pylori is an important cause of gastritis and a number of therapeutic trials suggest that it may be important in the genesis of duodenal ulcer recurrence. The reported prevalence of gastric colonisation by the organism varies considerably. The aim of this cross-sectional survey was to determine its prevalence in non-ulcer dyspeptics and to determine whether this is influenced by age, race, sex, socio-economic status, educational level and the number of persons sharing accommodation. One hundred and sixty-nine patients underwent endoscopy; biopsy specimens were taken from the antrum and H. pylori status was determined histologically. Gastric colonisation was found in 106 patients (63%). The prevalence showed a marked ethnic difference: 40% in whites and 71% in coloureds (P < 0.001). The ethnic groups were characterised by significant differences in socio-economic status (P < 10(-6)), educational level (P < 10( 6)), number of persons sharing accommodation (P < 10(-6)) and age (P < 0.001). These same differences were found when comparing the H. pylori-positive and negative groups, but were less marked and could be attributed to the marked differences between ethnic groups. We conclude that H. pylori prevalence differs between the ethnic groups studied. This may be because of varying degrees of exposure risk. PMID- 8511683 TI - Pap smear coverage among rural workers. AB - Despite the high incidence of cancer of the uterine cervix among black South African women, many do not have access to cytological screening services. Data describing Papanicolaou smear coverage and factors related to coverage are presented from 9 surveys of rural women workers in the food canning and processing industry in the Cape. Adequacy of Pap smear coverage was assessed according to whether the respondent had ever previously had a Pap smear, or had had one in the 3 years preceding the survey. From the 3 surveys with the greatest generalisability, only 49-65% of workers reported adequate Pap smear coverage. Knowledge about Pap smears was lacking. At the same time, of those women with adequate coverage, many appeared to be receiving unnecessary routine Pap smears. It appears that the policy which makes the availability of Pap smears dependent upon acceptance of contraceptive services is responsible for both the lack of Pap smear coverage and the over-provision of smears in this group of women. An urgent review of state Pap smear policy is required and a coherent community-based educational programme to facilitate the prevention of cervical cancer should be implemented as soon as possible. PMID- 8511684 TI - Seasonal and recurrent intensive care unit admissions for acute severe asthma in children. AB - Life-threatening attacks of asthma requiring intensive care unit (ICU) management at Red Cross War Memorial Children's Hospital in Cape Town were noted to occur in some patients in the same or adjacent months of different years. A retrospective case-controlled study was performed of 21 such 'seasonal' patients who presented to the ICU over a 14-year period. The group made up 6.5% of all asthma patients admitted to the ICU and their 65 admissions made up 15.6% of all ICU asthma admissions during this period. The control group consisted of patients with recurrent admissions that occurred in 'random' months. The two groups were compared in respect of demographic and clinical data. Patients requiring seasonal admissions were shown to form a distinct sub-population of children with severe asthma, some with a family history of fatal asthma, who were less likely to 'outgrow' asthma in childhood, were more likely to require maintenance steroid therapy for asthma management, and significantly more often had positive radioallergosorbent tests to Aspergillus and Cladosporium sp. and to grass pollen. A retrospective analysis of dates of severe asthma attacks may identify individual seasonality, which is a risk factor for life-threatening and intractable asthma. PMID- 8511685 TI - The social, family and medical backgrounds of children with kwashiorkor presenting at a teaching hospital. AB - The social, family and medical backgrounds of 53 children hospitalised with kwashiorkor were compared with those of 106 children hospitalised for non nutritional diseases to determine risk factors for severe nutritional disease in children presenting to a teaching hospital. The control children were matched for age, sex, race and the non-nutritional illness complicating the course of the children with kwashiorkor; in 80% of cases the reason for admission was either gastro-enteritis or pneumonia. A major difference between the groups was the educational status of the mothers. Only 57% of the mothers of the children with kwashiorkor were literate compared with 93% of the controls; 25% as opposed to 47% were married, and 36% as opposed to 72% received support from the father. There were no differences in the mothers' ages or use of contraception, or in the number of children they had. In all except 1 instance the child with kwashiorkor was the youngest or only child in the family, and the average sibling interval was 53 months. The types of dwellings occupied by the families were similar, but overcrowding was worse in the kwashiorkor group. Family income was below the household subsistence level in the vast majority of both groups, but significantly more of the kwashiorkor group had minimal cash income. Significantly fewer of the children with kwashiorkor had been breast-fed or adequately immunised, and 60% had previously been hospitalised for dehydrating diarrhoea. This study demonstrates that in an urban environment the traditional factors of large families and displacement by a younger sibling are not associated with kwashiorkor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511686 TI - The persistence of hepatitis B antigen in the bloodmeal of the potential medicinal leech, Asiaticobdella buntonensis. AB - The persistence of the hepatitis B virus surface antigen (HBsAg) was used as an index of the survival time of this virus within the gastro-intestinal tract of the potential southern African medicinal leech, Asiaticobdella buntonensis. HBsAg was tested for in blood/faecal material at five intervals over 15 weeks. Samples from both the midgut and the rectum remained positive for the entire test period, although with decreasing strength. The results are compared with reports on other arthropods which indicate increasing antigen persistence with increasing body size. The findings implicate medicinal leeches as mechanical vectors of HBV and possibly of other medically important viruses, and argue against using leeches of suspect or unknown origin in the alleviation of venous congestion in failing microsurgical procedures. PMID- 8511687 TI - Maternal nicotine exposure during pregnancy and development of emphysema-like damage in the offspring. AB - The aim of this investigation was to determine whether nicotine exposure (1 mg/kg body mass/d) during pregnancy and lactation contributes to the rupturing of alveolar septa in the lungs of neonatal rats. These rats received nicotine only via the placenta and mother's milk. The results show that maternal nicotine exposure interferes with elastic tissue formation. It also interferes with alveoli formation and causes the development of emphysema-like lesions. It is therefore suggested that maternal nicotine intake from smoking during pregnancy and lactation may interfere with lung development and maturation to an extent that increases susceptibility to emphysema. PMID- 8511688 TI - New estimates of infant and child mortality for blacks in South Africa, 1968 1979. AB - This report is part of a project to evaluate and improve the quality of mortality data for blacks in South Africa. Infant and child mortality rates of 79/1,000 and 81/1,000 were estimated for 1968-1974 and 1975-1979 respectively. A child mortality rate of 43/1,000 was estimated for 1973-1977. Estimates of infant mortality rates for 1970-1974 and 1975-1979, and the child mortality rate for 1973-1977, are higher than the results reported earlier by other analysts. PMID- 8511689 TI - Traditional Indian customs surrounding birth. A review. AB - Since 1960, only a few studies have been made of traditional customs surrounding birth in Indian culture. Very few of these have described customs followed by Indians in South Africa. A review of these publications is presented here. Customs described include religious, social and psychological aspects of behaviour in relation to conception, pregnancy, birth and the early months of parenthood. PMID- 8511690 TI - Adherence to traditional Indian customs surrounding birth. AB - Customs traditionally followed by Indian women during pregnancy, birth and early parenthood have been documented. An exploratory investigation of the extent to which some of these traditional beliefs, customs and practices are currently adhered to was undertaken by interviewing Indian mothers living in Johannesburg and its environs about 3 months after delivery. Results indicate that while some traditional customs are still adhered to by most Indian women, others are not so strictly followed. Since most customs relate to activities conducted at home rather than while in hospital for delivery, medical care would not be expected to influence their practice. PMID- 8511691 TI - Cultural issues in the psychiatric assessment of Xhosa children and adolescents. AB - Traditional healers living in Guguletu, Cape Town, were interviewed about their practices in order to ascertain whether or not there are cultural/indigenous expressions of psychological distress or dysfunction in black children and adolescents. Besides bedwetting, fits and school anxiety, five other 'syndromes' were described: ukuphambana, ukuphaphazela, amafufunyane, umoya and ukuthwasa. Although detailed case studies are required to establish the internal validity and exact nature of these 'syndromes', it is clear that any systematic study of psychiatric disorders in Xhosa children and adolescents needs to take them into account. PMID- 8511693 TI - A few thoughts on the history of epilepsy. AB - The history of epilepsy is a saga of the struggle by which scientific understanding of an unusual disease was gained by a long and circuitous route. In the beginning this affliction was attributed to demon possession and defied understanding for centuries when it was still regarded as a sacred disease and surrounded by superstition and mysticism; therapy of necessity had to follow similar lines of reasoning. The gradual realisation that cerebral dysfunction was the cause of this disease was highly significant although still followed by misunderstanding and misinterpretation--those two essential steps to progress. Clear, inspired reasoning and lucid clinical descriptions of epilepsy by John Hughlings Jackson and William Gowers set the scene for what was to follow. Experimental neurophysiology, cortical simulation, cortical localisation, new technologies of electro-encephalography, modes of visualisation of structures histologically and radiologically led to our present-day concepts of this complex disorder. We have been brought to new thresholds of understanding through the co operative exertions of many workers from all parts of the world and this saga tells of some of the highest scientific accomplishments in medicine. PMID- 8511692 TI - Two years of admissions to Natal's first inpatient child mental health centre. AB - The need for increased provision of mental health services for children has long been expressed. Equally, there is a shortage of training opportunities for mental health workers in this specialised field. The establishment of the first inpatient child mental health centre in Natal, together with clinical and demographic characteristics of the first 100 patients admitted to the unit, is discussed. Almost one-third of the children were diagnosed as having disruptive behaviour disorders, including conduct disorder, attention-deficit hyperactivity disorder and oppositional defiant disorder. Parent-child problems were also very prevalent. While a variety of therapeutic modalities were employed, behavioural management formed the mainstay of the treatment programme. Recommendations for additional child mental health centres are made. PMID- 8511694 TI - Compensation for occupational diseases--fact or legal fiction? PMID- 8511695 TI - Fluoride supplementation. PMID- 8511697 TI - Fluoride supplementation. PMID- 8511696 TI - Unproven cancer remedies. PMID- 8511698 TI - Absorption and effectiveness of a single povidone iodine douche during pregnancy. PMID- 8511699 TI - Poor quality of ECG tracings. PMID- 8511700 TI - False-positive trypanosome identification. PMID- 8511702 TI - A safer anaesthetic airway for paediatric adenotonsillectomy. PMID- 8511701 TI - A comparison of two doses of caudal morphine with bupivacaine in children undergoing major lower abdominal surgery. PMID- 8511703 TI - Lead levels in maternal and umbilical cord blood at King Edward Hospital, Durban. PMID- 8511705 TI - Risk profiles and epidemiologic interrelationships of sexually transmitted diseases. AB - In this study, the risk profiles and epidemiologic interrelationships of 13 sexually transmitted diseases (STD) were studied in 12,170 men and 6,125 women attending the Adelaide STD Clinic in South Australia from 1988 to 1991. Fifteen independent variables for men and 19 independent variables for women were analyzed by multiple logistic regression. Risk profiles were depicted graphically from the odds ratios of independent associations with the factors studied. These profiles showed a marked influence of socioeconomic factors on the epidemiology of hepatitis B infection, syphilis, scabies (in contrast with the pattern for pediculosis pubis), gonorrhea, and trichomoniasis. The risk profiles for warts, herpes, and molluscum contagiosum are similar and contrast with those of gonorrhea and chlamydia. The vaginitides showed clear differences, with bacterial vaginosis being directly associated with and candidiasis inversely associated with variables relating to sexual activity. In women, gonorrhea was a strong predictor of chlamydial infection and women with gonorrhea had twice the rate of other STDs collectively, compared with women who did not have gonorrhea. However, most other associations between individual STDs and other STDs collectively were of an inverse nature, although several strong associations between individual STDs were found on univariate analysis. PMID- 8511704 TI - Does addition of anti-inflammatory agents to antimicrobial therapy reduce infertility after murine chlamydial salpingitis? AB - BACKGROUND AND OBJECTIVES: Infertility after murine chlamydial salpingitis can be prevented by tetracycline treatment given before or at the time of infection. This study evaluates the efficacy and timing of tetracycline treatment and anti inflammatory agents in the prevention of inflammation and subsequent infertility. STUDY DESIGN: The left ovarian bursae and uterine horns were inoculated with the mouse pneumonitis strain of Chlamydia trachomatis. Mice were mated 54 days after inoculation. RESULTS: Infected mice treated with tetracycline beginning 2 days after infection showed mild inflammation and no significant reduction in fertility. However, when tetracycline treatment was delayed until 5 days after infection, a moderate degree of inflammation and a significant reduction in fertility (P < 0.01) was noted. Treatment with ibuprofen, prostaglandin E1 (PGE 1), or hydrocortisone beginning day 2 post-inoculation did not significantly alter the degree of inflammation or subsequent fertility. Mean anti-chlamydial IgG titers were significantly lower in mice treated with either PGE1 or hydrocortisone compared with infected, untreated mice. CONCLUSION: These results indicate that while early treatment of chlamydial salpingitis may prevent infertility, delay in treatment may result in significant inflammatory damage and infertility. There was no apparent benefit from the addition of anti-inflammatory agents. PMID- 8511706 TI - Prevention of vaginal trichomoniasis by compliant use of the female condom. AB - BACKGROUND: Several case-control studies suggest that the male condom protects women against some sexually transmitted diseases. The female condom is the first barrier device under the woman's control that may be effective in the prevention of sexually transmitted diseases. GOAL OF THIS STUDY: To determine if appropriate use of the female condom decreased the rate of recurrent vaginal trichomoniasis in previously diagnosed and treated women. STUDY DESIGN: One hundred and four sexually active women with vaginal trichomoniasis were treated with metronidazole and assigned to a group using the female condom or a control group during a 45 day period of continued sexual activity. Fifty women served as controls, and 54 women were assigned to use the female condom. RESULTS: Only 20 women used the female condom each time they had sexual intercourse. Reinfection with trichomonas occurred in 7/50 (14%) controls, in 5/34 (14.7%) noncompliant users, and in 0/20 compliant users of the female condom. CONCLUSION: The compliant use of the female condom is effective in preventing recurrent vaginal trichomoniasis. PMID- 8511707 TI - Confirmatory testing of Chlamydia trachomatis Syva enzyme immunoassay gray zone specimens by Syva direct fluorescent antibody test. AB - A series of gray zone specimens with sample to cutoff ratio of 0.7 to 0.99 encountered in routine use of the Syva Microtrak (Syva, Inc.) Chlamydia trachomatis enzyme immunoassay (EIA) test for urogenital specimens were subjected to repeat testing in duplicate and high-speed centrifugation with direct fluorescent antibody testing of the centrifugate. Immunofluorescent C. trachomatis elementary bodies were observed in high-speed centrifugates in more than 40% of two series of gray zone specimens examined indicating that a C. trachomatis gray zone result would require confirmatory testing. PMID- 8511708 TI - Gonorrhea, genital chlamydial infection, and nonspecific urethritis in male partners of women hospitalized and treated for acute pelvic inflammatory disease. AB - BACKGROUND AND OBJECTIVES: Acute pelvic inflammatory disease (PID) is often a complication to a sexually transmitted disease (STD), the most important agents being Neisseria gonorrhoeae and Chlamydia trachomatis. However, very little is known of the genitourinary status of the male partners of women with acute pelvic inflammatory disease (PID). GOAL OF THIS STUDY: To determine the presence of N. gonorrhoeae and/or C. trachomatis infection or nonspecific urethritis (NSU) in regular sexual male partners of women with acute PID. STUDY DESIGN: Two hundred regular sexual male partners to 196 women admitted to a hospital for treatment of acute PID were referred by contact tracing to the sexually transmitted disease outpatient clinic for clinical and laboratory examination regarding N. gonorrhoeae and/or C. trachomatis infection, or NSU defined as the presence of > 5 polymorphonuclear leukocytes per high-power field (x1,000) in > 4 fields and with negative laboratory tests for N. gonorrhoeae and C. trachomatis. RESULTS: The majority of the males was in the age group 20 to 29 years of age, female sexual partners in 15 to 24 years years of age. N. gonorrhoeae was demonstrated in 42.9% of the male partners to women with acute PID and concomitant gonorrhea. The corresponding figure for C. trachomatis was 43.7%. Nonspecific urethritis was diagnosed in 26 (33.8%) of the male partners to 77 women were diagnosed with N. gonorrhoeae and/or C. trachomatis infection, and in 45 (37.8%) partners of 119 women without such an infection. In all, N. gonorrhoeae, C. trachomatis or NSU were demonstrated in 117 (59.7%) of the 196 male partners, but only 32% of the males with N. gonorrhoeae or C. trachomatis and 8.5% of those with NSU presented subjective symptoms of urethritis. CONCLUSION: The findings of the study stress the need for routine clinical and laboratory examination and treatment of sexual male partners to women with acute PID. PMID- 8511709 TI - Screening urine with a leukocyte esterase strip and subsequent chlamydial testing of asymptomatic men attending primary care practitioners. AB - BACKGROUND AND OBJECTIVES: The detection of asymptomatic urethritis using a leukocyte esterase (LE) strip may have a role in primary care screening to select men who need diagnostic testing for Chlamydia trachomatis and Neisseria gonorrhoeae. STUDY DESIGN: Eight-hundred and eighty-two men, 16 to 35 years of age were studied when they attended their family physician or university health clinic for nongenitourinary complaints. First void urine (FVU) was tested by an LE strip (Chemstrip 2 LN, Boehringer Mannheim Corp., Indianapolis, IN), Chlamydiazyme (Abbott Laboratories, N. Chicago, IL) enzyme immunoassay with confirmatory blocking and polymerase chain reaction (PCR) with chlamydial plasmid primers. RESULTS: Forty-five men (5.1%) were positive (> trace) by LE strip. Of the LE-positive urines, 9 (20.0%) were positive by EIA or PCR, and none of the LE negatives were positive by EIA or PCR. Twenty-three LE positives (5 EIA/PCR positive; 1 PCR-positive; 17 EIA/PCR-negative) were able to be followed with a second urine and 2 urethral swabs. All of the 6 chlamydia-positives who had follow-up tests were positive by both immunoassay and PCR on urine. Based on the FVU results, the prevalence of asymptomatic chlamydial infection was 1.0% (9/88) (95% CL, 0.5 to 1.9) for which the LE urine strip was 100% (9/9) sensitive and 95.9% (837/873) specific. Analyses based on screening 1,000 men, 16 to 25 years of age, showed that the cost per case detected was $192.00 using the LE strip (> 1+) to select urine specimens for EIA testing, compared to $1,326.00 using the EIA to test all urine specimens. CONCLUSION: In this low prevalence, primary care setting, the LE urine strip was an accurate screening test, which if used to preselect urine specimens for subsequent chlamydial testing, would be less costly per case detected than assaying each specimen for chlamydia. PMID- 8511710 TI - Etiology of acute pelvic inflammatory disease proven by laparoscopy. AB - BACKGROUND: Only a few studies have investigated the etiology of acute pelvic inflammatory disease (PID) in laparoscopy-proven cases using pelvic samples for culture. Most of these studies were conducted in North America and Scandinavia. GOAL OF THE STUDY: To study the microbial etiology of laparoscopy-proven acute pelvic inflammatory disease in Israeli women. STUDY DESIGN: A prospective survey of women admitted to a hospital for treatment of acute pelvic inflammatory disease. All diagnoses were laparoscopy confirmed. Specimens for culture were obtained from the pelvic cavity via the laparoscope, and two serum samples were sent for serologic studies. RESULTS: Forty patients were studied. Their mean age was 34.4 years of age, and 27.5% had a history of PID. Chlamydia trachomatis infection was diagnosed in 14 (35%) patients (group A). Facultative and/or anaerobic bacteria were isolated from pelvic specimens of 7 (17.5%) patients (group B), one of these patients also had positive chlamydial serology. Mycoplasma hominis was cultured from a pelvic specimen of one woman, and herpes simplex virus grew from a pelvic sample of another patient in whom C. trachomatis was also found. In 19 (47.5%) women, the microbial etiology could not be determined (group C). In no case was Neisseria gonorrhoeae isolated. Stage I (mild) PID was diagnosed most often in group A (75% vs. 14% in group B [P < 0.02]), whereas the opposite was true for stage III (severe) PID (71.4% in group B vs 25% in group A [P = 0.07]). Tubal abscess was mainly diagnosed in group B patients (57% vs 16.6% in group A [P = 0.09]). CONCLUSION: In Israel, C. trachomatis is the most common cause of PID, while gonococci are rarely involved in this infection. PMID- 8511711 TI - Granuloma inguinale (donovanosis) in women. An analysis of 61 cases from Durban, South Africa. AB - BACKGROUND AND OBJECTIVES: Granuloma inguinale (GI) appears to be making a resurgence in South Africa. Local cases were reviewed in order to determine an increasing prevalence and whether differences appeared between pregnant and non pregnant women. STUDY DESIGN: Retrospective analysis of clinical records of patients attending a large tertiary teaching hospital, serving an underprivileged population. RESULTS: Sixty-one women with GI were diagnosed over a 3-year period. The most common clinical presentation was genital ulceration in both pregnant (88.5%) and nonpregnant (45.7%) patients. The next most common presentation was genital tract bleeding (19.7%), which occurred mainly among nonpregnant women. The vulva was the most frequent anatomical site involved (54.1%), in both pregnant (88.5%) and nonpregnant (28.6%) women. Multiple sites of infection (vulva, vagina, cervix) occurred only among nonpregnant women. Fourteen of 33 (42.4%) patients whose syphilis serology results were available had reactive tests. Erythromycin and tetracycline were the most common single antimicrobial agents used for therapy and response varied according to site and size of lesion. CONCLUSIONS: This study confirms our clinical impression of the increasing prevalence of GI, especially among women in Durban, South Africa. The protean manifestations of the disease are demonstrated with sharp distinctions between pregnant and nonpregnant women and there was a high prevalence of concomitant syphilis. PMID- 8511712 TI - Chlamydia trachomatis, infertility, and population growth in sub-Saharan Africa. AB - In sub-Saharan Africa, Neisseria gonorrhoeae and Chlamydia trachomatis are common infections. These pathogens are also the major causes of post-salpingitis tubal infertility, and infertility is a frequent problem in this region. A mathematical model, recently devised to estimate the effect of gonococcal infection on population growth, was used to estimate the potential effect of chlamydial infection on population growth. The model predictions for chlamydial infection were compared with those previously reported for gonococcal infection. The model predicts that both infections may be exerting severe effects on population growth at realistic prevalence rates of infection. The model also predicts that N. gonorrhoeae produces a steeper reduction in population growth than does C. trachomatis because its transmission dynamics result in a higher force of infection (incidence rate) at any given prevalence of infection. Large scale changes in the epidemiology of these infections can be expected to occur in sub Saharan Africa because of improved sexually transmitted disease (STD) diagnosis and treatment services as a component of AIDS prevention. Changes in the epidemiology of gonococcal and chlamydial infection are predicted to result in accelerated population growth unless STD control programs are linked to effective contraception programs. PMID- 8511713 TI - Sexually transmitted diseases and family planning. Strange or natural bedfellows, revisited. PMID- 8511714 TI - Expression of c-fos protein in the experimental epilepsy induced by pilocarpine. AB - The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system. PMID- 8511715 TI - Robustness of G protein changes in cocaine sensitization shown with immunoblotting. AB - Daily cocaine administration has been shown to alter G proteins in mesolimbic nuclei, and these changes have been implicated in the initiation and expression of behavioral sensitization. To evaluate the robustness of changes in G proteins induced by daily cocaine treatments capable of producing behavioral sensitization, the levels of Gi1 alpha, Gi2 alpha, Go alpha, Gs alpha, and G beta protein were measured by immunoblotting at 1 hr after an acute injection of cocaine or saline given 1 or 14 days following the last injection of daily cocaine or saline. A significant decline in Gi1 alpha was seen in the nucleus accumbens at 14 days following daily cocaine administration regardless of whether they received an acute challenge with cocaine or saline 1 hr prior to decapitation. No alterations were observed in the ventral tegmental area, substantia nigra, dorsolateral striatum, or prefrontal cortex in the levels of Gi1 alpha, Gi2 alpha, or Go alpha. No change in G protein immunoreactivity was measured in the nucleus accumbens or ventral tegmental area of rats decapitated 1 hr after discontinuing daily cocaine. The possibility that a long-term change in Gi1 alpha in the nucleus accumbens may be related to cocaine-induced behavioral sensitization is discussed. PMID- 8511716 TI - Identification of a GBR12935 homolog, LR1111, which is over 4,000-fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters. AB - The di-substituted piperazines, GBR12909 (1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3- phenylpropyl]piperazine) and GBR12935 (1-[2-(diphenyl methoxy)-ethyl]-4-(3-phenylpropyl)piperazine), are potent and selective (20-to 100-fold) inhibitors of [3H]dopamine reuptake, relative to [3H]5-HT and [3H]norepinephrine uptake. The GBR12935 analog, 1-(2-(diphenylmethoxy)ethyl)-4-(3 phenylpropyl)homopiperazine (LR1111), was synthesized as part of a systematic structure-activity study of analogs of GBR12935 and GBR12909. LR1111 differs from GBR12935 by the addition of a methylene group into the piperazine ring to yield a compound with a seven-member homopiperazine ring. The IC50 values for LR1111 at the dopamine, norepinephrine, and serotonin transporters were 7.2 nM, 34,072 nM, and greater than 20,000 nM, respectively, whereas the IC50 values of GBR12935 were 3.7 nM, 289 nM, and 1261 nM for these same transporters. This demonstrates that the addition of a single methylene group in the piperazine ring results in a compound with similar affinity but significantly higher selectivity for the dopamine transporter. LR1111 increased motoric activity in rats after intravenous administration. These indicate that LR1111 is a potent and highly selective inhibitor of the dopamine transporter. PMID- 8511717 TI - Biosynthesis of dopamine and serotonin in the rat brain after repeated cocaine injections: a microdissection mapping study. AB - The purpose of the present study was to examine the effects of chronic cocaine on dopamine (DA) and serotonin (5-HT) synthesis in several rat brain regions implicated in drug reinforcement. Male rats were treated twice daily with cocaine (15 mg/kg, ip) or saline for 1 week. After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip). Animals were decapitated 30 min after NSD-1015 and discrete brain regions were microdisected from 300 microns frozen sections. Postmortem tissue levels of 3,4-dihydroxyphenylalanine (DOPA) and 5-hyroxytryptophan (5-HTP) were quantified by HPLC with electrochemical detection and used to estimate biosynthesis of DA and 5-HT, respectively. In chronic saline-treated rats, cocaine dramatically suppressed DA and 5-HT synthesis in all forebrain regions examined, including: medial prefrontal cortex, nucleus accumbens, caudate nucleus, olfactory tubercle, and basolateral amygdala. The degree of inhibition ranged from 35-65% and was more pronounced in 5-HT neurons compared to DA neurons in the same tissue sample. In general, chronic cocaine did not significantly alter basal levels of DOPA or 5-HTP; a notable exception was lateral hypothalamus, where chronic cocaine reduced basal DA synthesis to 75% of control. After repeated cocaine injections, the synthesis-inhibiting effect of a challenge injection of cocaine was attenuated in many brain areas. These data suggest that whereas acute cocaine decreases DA and 5-HT synthesis in forebrain, chronic cocaine is not neurotoxic to DA and 5-HT neurons. In addition, the mechanism(s) mediating cocaine-induced suppression of monoamine synthesis may become desensitized by chronic exposure to the drug. PMID- 8511718 TI - Discrete expression of Ca2+/calmodulin-sensitive and Ca(2+)-insensitive adenylyl cyclases in the rat brain. AB - Physiological studies and inferences from invertebrate models implicate Ca2+/calmodulin-sensitive adenylyl cyclase with memory processes. However, Ca2+/calmodulin-insensitive adenylyl cyclase also occurs in brain, and its neuronal functions are less clear. Two oligonucleotide probes, based on rat cDNAs for Types I and II adenylyl cyclase, which appear to correspond to these functional forms, were used to conduct in situ hybridization analysis of the relative abundance and localization of these two species in the rat brain as a first step in evaluating their neuronal role. Quite discrete patterns of expression were encountered; in some areas, both species were co-expressed, but in others, little overlap was observed. The differential expression of the two mRNAs suggests that discrete roles may be fulfilled by the two adenylyl cyclases in neural tissues. PMID- 8511719 TI - Drug- and behavior-associated changes in dopamine-related electrochemical signals during intravenous heroin self-administration in rats. AB - High-speed chronoamperometry was used to monitor dopamine-related electrochemical signals in the nucleus accumbens of rats allowed to self-administer heroin intravenously and rats that received similar injections passively. Rats self administered 100 micrograms/kg of heroin at approximately 20-min intervals. Dopamine-related electrochemical signals increased monotonically after the first injection of each day; the effect was weaker on the first than on the second and subsequent days. The second and subsequent injections in each session caused biphasic effects: the initial effect was a decrease in signal--a minor one when compared to the increase caused by the first injection--and this was followed by an increase that brought the signal back to or somewhat higher than the level at the time of the injection. Over the course of each 4-h session, the electrochemical signal reached and fluctuated around an elevated plateau; doubling the injection dose did not elevate this plateau but did cause larger phasic decreases and subsequent increases. Qualitatively similar electrochemical changes were seen in the animals passively receiving the drug, but there were two notable quantitative differences. First, in the passive animals the initial depressions in signal were of shorter duration. Second, in the passive animals (which were injected at intervals determined by the self-administering animals) the electrochemical signal reached a maximum and began to fall prior to the time of the next injection; in the animals that self-administered the drug, the signal was still rising at the time of the next injection. The changes in electrochemical signal are unlikely to represent fluctuations of ascorbate or dopamine metabolites; thus it appears that whereas self-administered heroin injections cause a slow and long-lasting elevation of extracellular dopamine concentration, short-term increases in dopamine concentration are associated with the behavioral activation that precedes the injections and it is short-term decreases that appear to be associated with the period usually thought to be most significant for positive reinforcement. PMID- 8511720 TI - Withdrawal following cocaine self-administration decreases regional cerebral metabolic rate in critical brain reward regions. AB - The quantitative [14C]-2-deoxyglucose autoradiographic method was utilized to assess regional cerebral metabolic rate for glucose (rCMRglc) in rat brain during withdrawal from cocaine self-administration. RCMRglc was determined in 62 regions from brains of naive rats which were placed into an empty operant chamber for 12 hr continuously, and rats trained to self-administer cocaine during 3 hr training sessions and subsequently placed into the operant chamber for 12 hr continuously with or without access to cocaine. Animals placed into the chamber without access to cocaine were examined 6 hr later, while animals allowed access to the 12 hr cocaine binge were examined either 6 or 72 hr post-cocaine. Metabolic activity was reduced during withdrawal in the nucleus accumbens, olfactory tubercle, islands of Calleja region, basolateral and central amygdaloid nuclei, medial septum, piriform and cingulate cortices, rostral caudatoputamen, entopeduncular nucleus and the adjacent lateral hypothalamus, somatosensory, auditory, and motor cortices compared to the naive state. These effects were usually more severe at 72 than at 6 hr after binge exposure, with intermediate values observed in cocaine trained animals without binge exposure. The response was negatively correlated with the amount of cocaine consumed during binge exposure in the striatum, olfactory tubercle, piriform, cingulate, somatosensory, and motor cortices. Thus, the amount of cocaine consumed can affect the extent of metabolic depression after sustained drug exposure. The pattern of regional effects suggests that mesolimbic and rostral extrapyramidal dopamine terminal regions and certain of their efferent pathways are preferentially affected during cocaine withdrawal. The reduction of basal metabolic rate observed in these brain regions during cocaine withdrawal may become more severe with time despite the apparent recovery of certain behavioral-motivational responses. PMID- 8511722 TI - "Grateful Med" "Loansome Doc" are really serious learning. PMID- 8511721 TI - Expression of adenosine A1 receptors in cultured neurons from fetal rat brain. AB - The expression of adenosine A1 receptors was investigated using [3H]2-chloro-N6 cyclopentyladenosine (CCPA) in 8-day-old cultured neurons from fetal rat forebrain grown in serum-free medium. [3H]CCPA bound specifically and with high affinity (Kd = 2.9 nM) to a homogeneous population of sites. Displacement of CCPA binding by various adenosine derivatives indicated that A1 receptors were selectively labeled. The presence of Gpp(NH)p, a GTP analogue, reduced significantly the binding affinity (Kd = 12.2 nM), suggesting that A1 receptors detected in intact cultured cells are linked to associated G proteins. PMID- 8511723 TI - Confusion reigns: managed competition case management managed care. PMID- 8511724 TI - Legal issues for nurses. Patient incompetency & powers of attorney. PMID- 8511725 TI - Inhaled corticosteroids in COPD: awaiting controlled trials. PMID- 8511726 TI - Bronchodilators in infancy. PMID- 8511727 TI - Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction. AB - BACKGROUND: The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed. Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear. METHODS: A sequential placebo controlled, blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate (BDP), 750 micrograms or 1500 micrograms twice daily, and oral prednisolone, 40 mg per day, was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction (mean age 66 years, mean forced expiratory volume in one second (FEV1) 1.05 litres [40% predicted], geometric mean PD20 0.52 mumol). End points assessed were FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF), bronchial responsiveness to inhaled histamine, and quality of life as measured by a formal quality of life questionnaire. RESULTS: Both doses of BDP produced equivalent, small, but significant improvements in FEV1 (mean 48 ml), FVC (mean 120 ml), and PEF (mean 12.4 l/min). The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters. Inhaled BDP produced a treatment response in individual patients (defined as an improvement in FEV1, FVC, or mean PEF of at least 20% compared with baseline values) more commonly than placebo (34% v 15%). The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted. Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine. Small but significant improvements were seen in dyspnoea during daily activities, and the feeling of mastery over the disease. CONCLUSIONS: High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma. Both objective and subjective measures show improvement. Unlike asthma, no improvement in bronchial responsiveness was detected after six weeks of treatment. PMID- 8511728 TI - Effect of salbutamol on histamine induced bronchoconstriction in healthy infants. AB - BACKGROUND: The effect of inhaled beta 2 adrenergic drugs on infants with wheezing disorders remains controversial. Salbutamol inhibits the bronchial responsiveness of infants to histamine and nebulised water but whether or not it acts as a bronchodilator in this age group is unclear. The aim of the present study was to determine whether salbutamol can hasten the reversal of histamine induced bronchoconstriction in infants. METHODS: Bronchial challenge with histamine was performed in 40 infants aged 12 months or less with no previous history of respiratory symptoms. Response to histamine was assessed by forced partial expiratory flow/volume curves to measure maximal flow at functional residual capacity (VmaxFRC). After a fall of 40% or more from baseline VmaxFRC, each infant was randomly assigned to receive either salbutamol 0.5% or saline 0.9% solution by nebuliser. The rate of recovery of VmaxFRC and the time to reach baseline VmaxFRC were derived by linear regression. RESULTS: Infants who received salbutamol had a significantly faster rate of recovery (geometric mean 8.5 ml/s/min) than those who received saline (4.1 ml/s/min). Considerable interindividual variation was observed in the time from maximum bronchoconstriction to recovery of baseline VmaxFRC in both groups of subjects. CONCLUSIONS: Salbutamol significantly speeds the reversal of histamine induced bronchoconstriction in infants during the first 12 months of life. This observation provides further evidence to support the presence of functional beta adrenergic receptors in the airways of infants. PMID- 8511730 TI - Double blind trial of ionisers in children with asthma sensitive to the house dust mite. AB - BACKGROUND: Manufacturers of ionisers claim many benefits from the use of their devices, including the relief of asthma. Particles removed from the air are likely to include airborne allergens, so ionisers may achieve an effect by reducing the allergen load. METHODS: The effect of ionisers on airborne concentrations of house dust mite allergen Der p I was investigated in a double blind, crossover, placebo controlled trial in the homes of 20 children with allergic asthma. Subjects recorded their peak expiratory flow rate (PEFR) twice daily and completed a daily symptom score and treatment schedule on a diary card for two six week periods, one with an active ioniser and the other with a placed ioniser (randomly allocated) used in the living room and the bedroom. RESULTS: Airborne Der p I concentrations fell significantly during the active period compared with the placebo period, but there was no significant change in PEFR, symptom scores, or treatment usage. There was an increase in night time cough which almost reached significance during the active period. CONCLUSIONS: This study indicates that the use of ionisers cannot be recommended in the homes of asthmatic subjects to improve their symptoms. The significant reduction of airborne allergen concentrations may be of use as part of a multidevice allergen avoidance regimen, but the increase in night time cough requires further study. PMID- 8511729 TI - Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation. AB - BACKGROUND: Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS: Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS: Both bradykinin and histamine produced dose dependent increases in nasal airways resistance (NAR). There was no significant difference in the effects of bradykinin and histamine on NAR at any dose level. On a molar basis, however, bradykinin was 6.98 times more potent than histamine in inducing a 50% increase in NAR. Nasal challenge with bradykinin and histamine also induced significant rhinorrhoea compared with vehicle. The amount of rhinorrhoea induced by histamine was significantly greater than that induced by bradykinin at any dose level. Bradykinin and histamine induced dose dependent nasal pain and nasal itch respectively. When administered as single doses both bradykinin (1.9 mumol) and histamine (1.9 mumol) induced significant rhinorrhoea compared with the vehicle. The volume of rhinorrhoea secretions induced by histamine was 29% greater than that induced by bradykinin. In contrast, although NAR was increased significantly more by histamine than by the vehicle, the effect of bradykinin on NAR was significantly greater than histamine and vehicle in both magnitude and duration of effect. The incremental effect of bradykinin on lavage albumin levels was also significantly greater than both histamine and vehicle. CONCLUSIONS: This study shows that the nasal vascular effects of histamine are less prominent than its actions on rhinorrhoea, and that the greater obstructive effect of bradykinin than histamine on NAR may contribute to the relative lack of efficacy of H1 antihistamines on nasal blockage in clinical disease. PMID- 8511731 TI - Diagnosis of asbestosis by a time expanded wave form analysis, auscultation and high resolution computed tomography: a comparative study. AB - BACKGROUND: Crackles are a prominent clinical feature of asbestosis and may be an early sign of the condition. Auscultation, however, is subjective and interexaminer disagreement is a problem. Computerised lung sound analysis can visualise, store, and analyse lung sounds and disagreement on the presence of crackles is minimal. High resolution computed tomography (HRCT) is superior to chest radiography in detecting early signs of asbestosis. The aim of this study was to compare clinical auscultation, time expanded wave form analysis (TEW), chest radiography, and HRCT in detecting signs of asbestosis in asbestos workers. METHODS: Fifty three asbestos workers (51 men and two women) were investigated. Chest radiography and HRCT were assessed by two independent readers for detection of interstitial opacities. HRCT was performed in the supine position with additional sections at the bases in the prone position. Auscultation for persistent fine inspiratory crackles was performed by two independent examiners unacquainted with the diagnosis. TEW analysis was obtained from a 33 second recording of lung sounds over the lung bases. TEW and auscultation were performed in a control group of 13 subjects who had a normal chest radiograph. There were 10 current smokers and three previous smokers. In asbestos workers the extent of pulmonary opacities on the chest radiograph was scored according to the International Labour Office (ILO) scale. Patients were divided into two groups: 21 patients in whom the chest radiograph was > 1/0 (group 1) and 32 patients in whom the chest radiograph was scored < or = 1/0 (group 2) on the ILO scale. RESULTS: In patients with an ILO score of < or = 1/0 repetitive mid to late inspiratory crackles were detected by auscultation in seven (22%) patients and by TEW in 14 (44%). HRCT detected definite interstitial opacities in 11 (34%) and gravity dependent subpleural lines in two (6%) patients. All but two patients with evidence of interstitial disease or gravity dependent subpleural lines on HRCT had crackles detected by TEW. In patients with an ILO score of > 1/0 auscultation and TEW revealed mid to late inspiratory crackles in all patients, whereas HRCT revealed gravity dependent subpleural lines in one patient and signs of definite interstitial fibrosis in the rest. In normal subjects crackles different from those detected in asbestosis were detected by TEW in three subjects but only in one subject by auscultation. These were early, fine inspiratory crackles. CONCLUSION: Mid to late inspiratory crackles in asbestos workers are detected by TEW more frequently than by auscultation. Signs of early asbestosis not apparent on the plain radiograph are detected by TEW and HRCT with similar frequency. off PMID- 8511732 TI - Measurement of inspiratory muscle performance with incremental threshold loading: a comparison of two techniques. AB - BACKGROUND: Incremental threshold loading (ITL) is a test of inspiratory muscle performance which is usually performed by breathing through a weighted inspiratory plunger, the load on the inspiratory muscles being increased by externally adding weights to the intake valve. This is not a true threshold device and may be inaccurate. This method was compared with a true threshold device consisting of a solenoid valve which only opens to supply air at a predetermined negative mouth pressure. METHODS: Six naive, normal subjects (three men and three women) aged 22-24 years underwent three tests using each system. The inspiratory loads were increased every minute by equivalent amounts, -10 cm H2O with the solenoid valve and by 50 g with the weighted plunger, until the subjects could not inspire or sustain inspiration for a full minute. Six experienced subjects (four men and two women) aged 23-41 years were subsequently randomised to perform ITL with the solenoid valve, twice with the breathing pattern fixed and twice free. RESULTS: The solenoid valve generated a more accurate mouth pressure response and was less variable at higher loads than the weighted plunger. The work performed (expressed as the pressure-time product) was less with the solenoid valve but was more reproducible. ITL with the solenoid valve was not influenced by controlling the breathing pattern of the subjects. CONCLUSIONS: The solenoid valve has several features that make it superior to the weighted plunger as a device for ITL. It generates a more accurate mouth pressure response which is less variable at higher loads. Increases in load are smoother and quicker to introduce. ITL with the solenoid valve is not influenced by varying breathing patterns and does not require any external regulation. PMID- 8511733 TI - Surgical correction of nasal obstruction in the treatment of mild sleep apnoea: importance of cephalometry in predicting outcome. AB - BACKGROUND: A study was undertaken to determine if cephalometric radiographs could identify those who will benefit from nasal surgery in patients with a sleep apnoea hypopnoea syndrome (SAHS) and chronic nasal obstruction. METHODS: Fourteen patients with SAHS were enrolled. Those with normal posterior airway space and mandibular plane to hyoid bone distances on preoperative cephalometric radiographs were matched with those with abnormal cephalometry for the frequency of sleep disordered breathing and body mass index. Polysomnographic studies (all subjects) and nasal resistance measurements (n = 10) were performed one to three months before and two to three months after surgery (septoplasty, turbinectomy, and polypectomy). RESULTS: There was no difference in the baseline results of the polysomnographic studies between the two groups of patients. Nasal resistance decreased from a mean (SE) value of 2.9 (0.3) cm H2O/l/s before surgery to 1.4 (0.1) cm H2O/l/s after surgery in the normal cephalometry group and from 2.7 (0.3) cm H2O/l/s to 1.3 (0.3) cm H2O/l/s in the other group. The apnoea + hypopnoea index returned to normal (< 10 breathing abnormalities/hour) in all but one subject with normal cephalometric measurements, and sleep fragmentation improved with a decrease in the arousal index from 23.9 (3.3)/hour at baseline to 10.6 (2.5)/hour after surgery. Both of these parameters remained unchanged after surgery in the patients with abnormal cephalometry. CONCLUSIONS: Normal cephalometry is helpful in identifying patients with mild SAHS and nasal obstruction who will benefit from nasal surgery. The presence of craniomandibular abnormalities makes it unlikely that nasal surgery will improve sleep related breathing abnormalities. PMID- 8511734 TI - A study of Spanish sepiolite workers. AB - BACKGROUND: Sepiolite is an absorbent clay that is used as pet litter. It forms thin crystals, which are a transition between chain and layered silicates. Inhalation studies in animals have shown no evidence of pulmonary damage. This paper reports a cross sectional study of the total work force of the largest sepiolite production plant in the world. METHODS: Two hundred and eighteen workers (210 men and eight women) were studied. Height, age, and smoking history were recorded. Chest radiographs were read according to the International Labour Office (ILO) classification by two readers. Readings were used to construct a numerical score, which was then used in statistical analyses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were divided by the square of the height. Casella size selective personal samplers were used in randomly selected operatives to collect dust eight years before the rest of the study was carried out. These samples were evaluated gravimetrically. Total dust samples were examined by optical and electron microscopes. Results were analysed by bivariate linear regression, chi 2 tests, and analysis of variance. RESULTS: When allowance was made for smoking habit workers exposed to dry dust showed a significantly greater decline in FEV1 with age than workers with little exposure to dry dust. A similar pattern applied to FVC. Radiographic score showed deterioration with age but no clear differences from other variables. High concentrations of dust were found in the bagging department and also in the classifier shed. CONCLUSIONS: The major finding was that lung function deteriorated more rapidly in those who had had more exposure to dust, but there was no evidence of any accompanying radiographic change. PMID- 8511735 TI - Body weight and weight gain related to pulmonary function decline in adults: a six year follow up study. AB - BACKGROUND: Obesity increases the risk of cardiovascular disease, hypertension, diabetes, digestive diseases, and some cancers. Several studies have shown that excess weight or weight gain is related to pulmonary dysfunction, but this issue needs to be further clarified. METHODS: The analysis was based on data of the Humboldt cohort study which was conducted in the town of Humboldt, Saskatchewan, Canada. The baseline survey in 1977 included 1202 adults, comprising 94% of all residents aged 25-59 years. Of these, 709 (59%) were followed up in 1983. Pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid expiratory flow rate (MMFR) and weight were measured in both surveys. Weight gain was determined by subtracting weight at baseline from weight at follow up. A residual analysis was used to examine the relationship between body mass index (BMI) at baseline, weight gain, and pulmonary function decline. RESULTS: Both BMI at baseline and weight gain were significantly related to pulmonary function at follow up. The effect of weight gain during the study period, however, was more prominent. The results showed that both mean residual FVC and FEV1 were highest in the group that gained < 1.0 kg, lowest in the group that gained > or = 4.0 kg, and intermediate in the group that gained 1.0-3.9 kg in both men and women after taking age, BMI at baseline, and smoking into account. The effect of weight gain on pulmonary function was greater in men than in women. Multiple regression analysis showed that each kilogram of weight gain was associated with an excess loss of 26 ml in FVC and 23 ml in FEV1 in men, and 14 ml and 9 ml respectively in women. CONCLUSIONS: Weight gain is significantly related to lung dysfunction. The effect of weight gain on pulmonary function is greater in men than in women. PMID- 8511736 TI - Static lung volumes in healthy subjects assessed by helium dilution during occlusion of one mainstem bronchus. AB - BACKGROUND: Single lung function is usually assessed by radioisotopes or, more rarely, by bronchospirometry in which a double lumen catheter is used to separate ventilation of the two lungs. The latter is more precise but less comfortable. An alternative bronchoscopic method is described for determining the volume of a single lung. METHODS: One mainstem bronchus was temporarily occluded with an inflatable balloon during fibreoptic bronchoscopy in 12 healthy volunteers aged 18-29 years. The functional residual capacities (FRC) of the right, left, and both lungs were measured in duplicate by closed circuit helium dilution. Supplementary vital capacity (VC) manoeuvres permitted calculation of single lung capacities (TLC) and residual volumes (RV). RESULTS: The standard deviation of a single determination of capacities of the right, left, and both lungs were: TLC, 80, 96, and 308 ml; VC, 56, 139, 171 ml; FRC, 131, 74, and 287 ml; RV, 112, 185, and 303 ml, respectively. The sum of the right and left unilateral TLC was not different from bilateral TLC (6.12 v 5.95 l) and the sum of the unilateral FRC was not different from the bilateral FRC (2.60 v 2.78 l). The sum of the unilateral VC was lower than bilateral VC (4.52 v 4.80 l), that of the unilateral RV was higher than bilateral RV (1.60 v 1.16 l). For all subdivisions of lung volume, the right lung was larger than the left. The most common complaint was substernal discomfort during complete exhalation. Oxygen saturation rarely fell below 90%. CONCLUSIONS: Temporary occlusion of a mainstem bronchus in normal subjects is safe, relatively simple, and allows fairly precise and accurate measurements of unilateral static lung volumes. Occlusion at TLC, however, probably prevents proper emptying of the non-occluded lung. PMID- 8511737 TI - Glycerol particle cigarettes: a less harmful option for chronic smokers. AB - In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour. PMID- 8511738 TI - Histological examination of peroperative frozen sections in suspected lung cancer. AB - BACKGROUND: Despite extensive investigations some patients with suspected lung cancer may undergo thoracotomy without preoperative histological proof of malignancy. A questionnaire on the use of histological examination of peroperative frozen sections in such patients was sent to 50 thoracic surgeons. Replies were received from 41 surgeons and indicated an absence of consensus on the usefulness of histological examination of frozen sections in this context, confirming the need for this study. METHODS: During one year 60 consecutive patients undergoing thoracotomy for suspected lung cancer without a prior histological diagnosis were studied prospectively. At thoracotomy the surgeon assessed the lesion macroscopically and a verdict on whether it was malignant was recorded. A biopsy specimen was then taken for examination of a frozen section and the result recorded. The appropriate operation was performed and the surgeon's verdict and the report on the frozen section were compared with the definitive histological diagnosis based on a paraffin section. RESULTS: Of 50 malignant lesions, 43 were identified by the surgeon and 47 by examination of the frozen section (sensitivity 86% and 94% respectively). Of 10 benign lesions, four were identified by the surgeon and nine by examination of the frozen section (specificity 40% and 90% respectively). CONCLUSIONS: Clinical and macroscopic assessment at thoracotomy are inferior to examination of frozen sections in suspected lung cancer, particularly where the lesion is benign. Lung resection should not be performed without examination of peroperative frozen sections when thoracotomy is performed for suspected but unproved lung cancer. PMID- 8511739 TI - New perspectives on basic mechanisms in lung disease. 5. Respirable industrial fibres: mechanisms of pathogenicity. PMID- 8511741 TI - Treatment of resistant pain in hypertrophic pulmonary arthropathy with ketorolac. AB - Pain associated with hypertrophic pulmonary osteoarthropathy (HPOA) may be extremely disabling and resistant to treatment. The successful use of ketorolac, a new non-steroidal anti-inflammatory drug, given by subcutaneous infusion is reported in two patients with uncontrolled pain caused by HPOA. PMID- 8511740 TI - A role for capsaicin sensitive, tachykinin containing nerves in chronic coughing and sneezing but not in asthma: a hypothesis. PMID- 8511742 TI - Miliary pulmonary cryptococcosis in a patient with the acquired immunodeficiency syndrome. AB - A 33 year old man with AIDS presented with fever, dyspnoea, cough and a miliary pattern on the chest radiograph. Cryptococcus neoformans infection was diagnosed from bronchoalveolar lavage bronchoscopy. This case supports the principle that, in patients with AIDS, pulmonary infections can exhibit variable radiographic features and that definitive diagnosis should always be considered. PMID- 8511743 TI - Combined oesophageal adenocarcinoma and carcinoid in Barrett's oesophagitis: potential role of enterochromaffin-like cells in oesophageal malignancy. AB - A case of combined adenocarcinoma and carcinoid tumour which occurred in a patient with a Barrett's oesophagus is presented. Its significance is discussed in relation to the potential role of enterochromaffin-like cells in the development of oesophageal malignancy, and the possibility is raised that long term treatment with omeprazole, commonly used in this condition, could promote this. PMID- 8511744 TI - Suture granuloma simulating lung neoplasm occurring after segmentectomy. AB - A suture granuloma was resected which developed after segmentectomy of a squamous cell carcinoma of the lung and radiologically mimicked a neoplasm. This report emphasises that although the appearance of the lesion may be typical for malignancy, the possibility of a benign suture granuloma should be considered, especially if the lesion appears shortly after surgery. PMID- 8511745 TI - Malignant mesenchymoma of the chest wall in an adult. AB - Mesenchymoma (hamartoma) of the chest wall is an extremely rare tumour presenting in early infancy or fetal life. Pleural, pulmonary, and lymph node metastases developed in a young man with malignant mesenchymoma of the chest wall. The tumour had several characteristics that differ from the mesenchymoma reported from the other parts of the body. PMID- 8511746 TI - Liposarcomatous differentiation in diffuse pleural mesothelioma. AB - A case history is presented of a woman who died eight hours after hospital admission with severe breathlessness. At necropsy the right lung was encased in a thickened pleura with a large tumour. Histological examination of the tumour showed pleural mesothelioma with liposarcomatous differentiation. The lungs showed changes of asbestosis and the asbestos fibre count was significantly raised. Liposarcomatous differentiation in pleural mesothelioma has not been reported previously. PMID- 8511747 TI - Attenuation of exercise induced asthma by local hyperthermia. PMID- 8511748 TI - Effect of dietary sodium on the severity of bronchial asthma. PMID- 8511749 TI - Notification of tuberculosis: how many cases are never reported? PMID- 8511750 TI - The hemostatic system and coronary heart disease. PMID- 8511751 TI - Platelet amino acid profile in control subjects. PMID- 8511752 TI - In vitro lupus anticoagulant neutralizing activity of intravenous immunoglobulin. PMID- 8511753 TI - Pharmacokinetics, absorption, distribution and disposition of [125I]-defibrotide following intravenous or oral administration in the rat. AB - Defibrotide (D) was labelled with 125I. The radiolabelled compound ([125I] Defibrotide ([125I]-D)) retained the same profibrinolytic activity as the parent drug. Following single intravenous administration of [125I]-D the half lives of radioactivity associated with D components in plasma were 9.45 min and 11.27 h for alpha and beta phases respectively. Following single oral administration of [125I]-D the half life of radioactivity associated with D components in plasma was 12.83 h for the elimination phase. Bioavailability was apparently 58%. The areas under plasma total radioactivity versus time curves were dose-dependent following both intravenous and oral administration. No significant accumulation of total radioactivity in plasma was observed following multiple oral administration of [125I]-D. Following single intravenous administration of [125I] D a larger proportion of administered radioactivity was excreted via urine than faeces while following single oral administration excretion via urine and faeces accounted for similar proportions of administered radioactivity. Following both single and oral administration the levels of total radioactivity in tissues and organs examined were generally highest in highly perfused organs and were very high in the thyroid despite pretreatment with non-radiolabelled potassium iodide. Radioactivity was also found to be associated with the aorta wall. PMID- 8511754 TI - The effect of secreted heparin-binding proteins on heparin binding to platelets. AB - Heparin is known to bind to activated platelets at two classes of sites. However, the true affinities of these sites for heparin have been uncertain because the measurements have been made in the presence of heparin-binding proteins secreted by the platelets. Of these proteins platelet factor-4 (PF4) has the greatest affinity for heparin and is present in relatively high concentrations. Furthermore, a portion of the secreted PF4 binds to the platelet surface. Nevertheless, by gel-filtering platelets in the presence of 5 micrograms/ml heparin, we prepared platelets that were virtually free of PF4. The high and low affinities of these cells for heparin were respectively ten- and two-fold greater than the apparent affinities measured in the presence of the secreted platelet proteins. In contrast, neither the high- nor the low-affinity heparin binding capacity of these cells was altered, indicating that PF4, even though it binds to both heparin and platelets, appears not to link heparin to platelets. PMID- 8511755 TI - [Findings in goats at necropsy]. AB - An overview is given of the results of diagnostic investigations into the cause of death of 463 goats performed by the Animal Health Service of West and Middle Netherlands during the period 1 January 1986 to 31 December 1991. The results are discussed and analysed with regard to the age of the animals, the anamnesis, and the abnormalities found at post-mortem examination and with regard to the results of further parasitological, bacteriological, and virological investigations. Enterotoxaemia caused by (epsilon-toxin-positive) Clostridium perfringens was present in 9% of the animals and fibrinous pneumonia with pasteurella in 15% of the animals. Animals with Aujeszky's disease did not show the 'itching' symptom. There were few parasitic infections. PMID- 8511756 TI - [A horse with grass sickness]. AB - A three year old warm-blood gelding with severe colic was referred to a veterinary clinic. The history revealed that the horse was found early in the morning with severe colic, and laying in the pasture. On arrival the clinical examination showed a complete wet horse with a pulse rate of 92/min, a respiratory rate of 24/min., a pcv of 0.50 L.L.-1, a T. of 38.0 degrees C, and no gastric reflux. Rectal examination revealed a sticky rectal mucous membrane and a colonic impaction together with displacement of the large colon. A diagnostic laparotomy showed an impaction as is seen in horses with Grass sickness. After euthanasia the coeliac ganglion was removed and histology showed dystrophy and chromatolysis, degenerative changes found in horses with Grass sickness. PMID- 8511757 TI - [Ethics and new technological applications in animals]. AB - Cloning and genetic engineering of animals are in the picture of public debate. The intrinsic value is an important issue in the ethical debate about both new technologies. The intrinsic value is introduced during the seventies as counterpart of the instrumental use of animals. The introduction of two new aspects, 'the ability to function independently' and 'naturalness', gives more insight in the meaning of intrinsic value. In two cases the consequences of the recognition of intrinsic value is discussed. The author concludes that cloning and genetic engineering are an infringement of the intrinsic value. The ethical debate about the transgenic bull Herman is the first experience in practice. PMID- 8511759 TI - [Deworming campaign in dogs and cats]. PMID- 8511758 TI - [Causes of the current newcastle disease problems]. PMID- 8511760 TI - [Adverse effects of calcium chloride]. PMID- 8511761 TI - [Tick fever]. PMID- 8511762 TI - [A heifer with severe calving problems]. PMID- 8511763 TI - Different exocytotic morphology in amphibian prolactin and growth hormone cells stimulated in vitro with TRH. AB - Exocytotic process in growth hormone (GH) and prolactin cells (PRL) of the frog anterior pituitary have been examined using an experimental design that has been previously demonstrated to increase the release of hormone from both cell types. Hemipituitaries of the same animals were superfused either with medium alone or containing 100 ng/ml of thyrotropin-releasing hormone (TRH) for 24 hr. PRL and GH cells were identified by the colloidal gold method using anti-human prolactin and anti-ovine growth hormone as primary antisera. In hemipituitaries cultured with medium alone, PRL and GH cells showed few exocytotic figures with different morphology in both cells types. In TRH treated hemipituitaries, PRL cells showed numerous exocytotic vacuoles containing immunoreactive granulated material that was preferentially located near basal lamina. On the other hand, GH cells showed higher amount of exocytotic vacuoles containing heterogeneous immunoreactive material, located along the cell membrane. In PRL cells single secretory granules are secreted, whereas GH cells showed multigranular exocytosis. These results indicate that in PRL and GH amphibian cells exocytotic process has a different polarity and morphology and that this process increases with TRH stimulation. PMID- 8511764 TI - A study of wound healing in the E11.5 mouse embryo by light and electron microscopy. AB - In this paper we report our light and electron microscopic studies of the healing of a simple excisional lesion to the E11.5 mouse embryo hindlimb. The wounded living embryo is cultured in a roller bottle and under such conditions the lesion is completely re-covered with epithelium by 24 hr. We discuss how our studies of such a simple wound healing model may offer insight into the mechanisms of tissue repair generally. PMID- 8511765 TI - Protein and lipoprotein uptake by developing oocytes of the hawkmoth Manduca sexta. An ultrastructural and immunocytochemical study. AB - The ultrastructure of developing Manduca sexta oocytes is described with respect to the endocytic pathway for protein incorporation. Three major (lipo) protein components of mature M. sexta eggs, lipophorin, vitellogenin and microvitellogenin, were localized along this pathway by immuno-fluorescence and immuno-gold labeling techniques. Labeling of the antigens was observed in the extracellular spaces of the follicle. In those cases where fixation and en bloc staining procedures did not destroy antigenicity, antigens were detected in coated pits and coated vesicles near the plasma membrane of the oocyte. All three antigens were demonstrated to be present in endosomes in the cortex of the oocyte. Both the morphology and the labeling pattern of the endosomes indicate that this organelle is a compartment of uncoupling of receptor and ligand. Tubular elements at the surface of the endosome, interpreted to be involved in the recycling of receptors and membrane to the oocyte surface, were not labeled. Strong labeling of lipophorin, vitellogenin and microvitellogenin was observed in the developing yolk bodies, the main protein storage compartment of the oocyte. The uptake and storage of hemolymph proteins and lipoproteins by M. sexta oocytes is discussed in comparison with other insect and vertebrate endocytic systems. PMID- 8511766 TI - Endocrine-like cells and insulin-binding sites in the epineurium of Helix pomatia. AB - Endocrine/paracrine-like cells are described for the first time in the epineurium of the cerebro-subesophageal ganglia connectives and in the epineurium of the nervus pallialis dexter et internus of Helix pomatia. At least a population of these cells contains insulin-immunoreactive material. Immunoelectron-microscopic investigations showed that electron-dense granules exhibit insulin-like material. Insulin-binding studies revealed granular cells as putative target-cells of insulin in the epineurium. PMID- 8511767 TI - The dynamics of intramembranous particles in the degradative pathways of the phagocytosed erythrocyte. AB - The present study was designed to reveal membrane events during an erythrophagocytosis by electron microscopy. The erythrocytes, which were extravasated into rats' mesenteric lymph node sinuses by short clamping of the portal-vein and phagocytosed by fixed macrophages, were analysed at 0.5, 1, 3, 4 and 6 hr after reopening of the vein by using freeze-fracture and thin-section techniques. The results were as follows: the intramembranous particles of the phagocytosed erythrocyte aggregated after injection of lysosomal enzymes into the phagosome. The digested cytoplasm accumulated in the space between the phagosomal and erythrocyte membranes and was removed from the phagosome by bleb formation or invagination. Subsequently, the erythrocyte membranes lost their intramembranous particles and fragmented. The phagosome lost its density and erythrocyte structure and became a vacuole (phagosomal ghost), which fractured lamellarly. PMID- 8511768 TI - The planes of division in twin cell doublets. AB - The fifth stage larval epidermis of Calpodes ethlius (Lepidoptera, Hesperiidae) is a syncytium of doublets where sibling cells remain connected by residual midbodies between mitoses. These twins resemble one another more than their other neighbours in features such as the shape and number of nucleolar particles, the number of actin bundles, the position of condensed chromosomes in female cells and the timing of mitosis. Although the patterns of arrangement of structures may be similar in twinned nuclei they differ in their orientation. We have now found that twins also differ in the orientation of their division planes with respect to the previous plane of division. Similarity of structural pattern but not orientation is most easily explained if nuclei, together with determinants for the plane of division, are free to rotate in the plane of the epithelium. PMID- 8511769 TI - The timing of division in twin cell doublets. AB - The fifth stage larval epidermis of Calpodes ethlius (Lepidoptera, Hesperiidae) is a syncytium of doublets where sibling cells are twins connected by residual midbodies between divisions. Twin cells resemble one another more than their other neighbours in such features as the shape and number of nucleolar particles, the number of actin bundles and the position of condensed female chromosomes. We have now found that they also resemble one another in the timing of cell division in preparation for pupation. Twins are more likely to divide together than at random. The paired timing of mitosis is presumed to be a result of the twins sharing a common cytoplasm. PMID- 8511770 TI - Evidence that Muller cells can phagocytize egg-lecithin-coated silicone particles. AB - This study is designed to better understand the function of the Muller cells of the retina through the use of silicon particles that had been injected into the vitreous body of the eye and via an analysis of the number of gap junctions associated with these cells. Following intraocular injection of a silicone oil mixture into the rabbit retina, numerous small silicone particles less than 1 micron in diameter were found attached to the basement membrane of the inner limiting membrane, subjacent to the Muller cells. On the sites to which the silicone particles attached, the basement membrane was reduced in thickness or completely disappeared. The 'end-feet' of the cell membrane facing the silicone particles became concave appearing as if they were in the process of incorporating the particles into the cell. Similarly, the Muller cells occasionally extended cytoplasmic processes through the basement membrane and towards the silicone particles, as if to engulf them. Gap junctions were observed but only in association with the Muller cells. They were often found between the 'end-feet' of adjacent Muller cells or the 'end-feet' of one cell and very thin cytoplasmic process of a neighboring cell. On rare occasions, they were located between 'end-feet' of the same Muller cell. The percentage of 'end-feet' displaying gap junctions was 38 +/- 8% (mean +/- SE). These data suggest that the Muller cells are important in the maintenance of normal retinal function by their ability to phagocytize foreign substances and by their ability to transmit information to various parts of the retina through cell-to-cell connections established by gap junctions. PMID- 8511771 TI - Development of in vitro Vmax and Km values for the metabolism of isofenphos by P 450 liver enzymes in animals and human. AB - The rate of metabolism of [14C]isofenphos (IFP) to isofenphos oxon (IFP-oxon), des N-isofenphos (d-N-IFP), and des N-isofenphos oxon (d-N-IFP-oxon) by rat, guinea pig, monkey, dog, and human liver microsomal P-450 enzymes was studied to obtain Vmax and Km values for Michaelis-Menten kinetics. The monkey had the highest Vmax value for the conversion of IFP to IFP-oxon (desulfuration), 162 nmol isofenphos hr-1 per 1.3 nanomoles P-450, followed by guinea pig (98), rat (66), dog (43), and human (14). The Km values for the desulfuration of isofenphos were 19.2, 7.4, 14.1, 23.3, and 18.4 microM, respectively, for the monkey, guinea pig, rat, dog, and human. The Vmax values for the dealkylation process (conversion of IFP to d-N-IFP) were 64.6, 17.2, 9.7, and 7.3 nmol isofenphos hr-1 per 1.3 nanomoles P-450 for the monkey, rat, dog, and human, respectively. For the dealkylation process, monkey had the highest Km value, 16.3 microM IFP, followed by human (11.2), rat (9.9), and dog (9.3). The rate of metabolism of IFP oxon and d-N-IFP to d-N-IFP-oxon were separately studied. The Vmax and Km values obtained in this study for animal and human liver P-450 enzymes will be used to develop a PB-PK/PB-PD model to predict the fate and toxicity of isofenphos in animals and man. PMID- 8511772 TI - Cytotoxic and genotoxic activity of 1,3-dichloropropene in cultured mammalian cells. AB - 1,3-Dichloropropene (DCP), a widely used soil fumigant previously found to be carcinogenic in both mice and rats, was evaluated for its cytotoxic and genotoxic effects in cultured rodent and human cells. A reduction of cell viability that was dependent on the dose and the length of treatment was observed with the trypan blue and the neutral red assay in both V79 cells and rat hepatocytes exposed to DCP concentrations ranging from 0.18 to 5.6 mM. In the absence of a metabolic activation system, a dose-dependent frequency of DNA single-strand breaks, that were only partially repaired within 24 hr, was revealed by the alkaline elution technique in V79 cells exposed to subtoxic DCP concentrations. The genotoxicity of DCP was confirmed by the results obtained in metabolically competent primary cultures of both rat and human hepatocytes which displayed similar dose-related amounts of DNA fragmentation and DNA repair synthesis, and showed, in comparison to metabolically deficient V79 cells, a somewhat greater sensitivity to the cytotoxic and DNA-damaging effects of DCP. The increase in the frequency of DNA breaks observed in rat hepatocytes after GSH depletion confirms the role of this tripeptide in DCP detoxification; its reduction in hepatocytes simultaneously exposed to metyrapone is consistent with a cytochrome P450 dependent biotransformation of DCP to more toxic metabolites. PMID- 8511773 TI - Genotoxic activity of 1,3-dichloropropene in a battery of in vivo short-term tests. AB - The genotoxic activity of 1,3-dichloropropene, which has been classified as possibly carcinogenic to humans, was investigated in rats given high single doses of this chloroolefin. A dose-related amount of DNA fragmentation was observed at doses ranging from 62.5 to 250 mg/kg in liver and gastric mucosa, both of which are targets of DCP carcinogenic activity, as well as in the kidney. The frequency of DNA breaks, that were to a large extent repaired within 24 hr, was higher after po than after ip administration in the liver, while the converse occurred in the kidney. Any evidence of DNA fragmentation was, in contrast, absent in lung, bone marrow, and brain which are not sites of DCP-induced tumor development. A role of cytochrome P450 in the activation of DCP is suggested by the lower degree of liver DNA fragmentation observed in rats pretreated with methoxsalen. DCP produced a dose-dependent reduction of the liver GSH level, an effect that presumably hinders its detoxification and thus favors its DNA damaging activity. In contrast with the satisfactory prediction of DCP carcinogenic activity provided by the results of the in vivo DNA damage/alkaline elution assay, neither the in vivo rat hepatocyte DNA repair assay nor the micronucleus assay, carried out on bone marrow, spleen, and liver cells of partially hepatectomized rats, supplied any evidence of DCP genotoxicity. PMID- 8511774 TI - A pharmacodynamic model of triglyceride transport and deposition during feed deprivation or following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat. AB - A simplified model of fat metabolism was developed to predict fat synthesis, transport, deposition, and metabolism as a function of feed consumption, as a means of testing mechanisms proposed for the disruption in fat metabolism caused by TCDD. Rates of triglyceride (TG) synthesis and lipolysis were made directly dependent on daily average levels of feed consumption, which could be constant or follow other patterns. Seven compartments, including plasma very low density lipoprotein (VLDL) (1), plasma free fatty acid (FFA) (2), plasma VLDL remnants (3), lipoprotein lipase (LPL)-VLDL complex (4), liver TG (5), white adipose tissue (WAT) TG (6), and brown adipose tissue (BAT) TG (7) were required to obtain realistic rates of TG deposition in storage fat while maintaining normal levels of plasma TGs and FFA. The steady-state level of hepatic TG was very sensitive to the rate of storage fat lipolysis and hepatic VLDL export. Because plasma TG is taken up very rapidly by extra-hepatic tissues, reduction of WAT uptake rates had a greater effect on plasma TG than increasing rates of hepatic synthesis and VLDL export. Our results indicate that neither increased hepatic VLDL synthesis nor a simple inhibition of WAT LPL can, by themselves, explain the combined occurrence of hyperlipidemia and loss of fat observed in TCDD-treated animals. However, a TCDD-mediated enhancement of WAT TG lipolysis and consequential physiological responses in liver and BAT yield results compatible with experimental data. PMID- 8511775 TI - Pulmonary toxicity of deferoxamine in iron-poisoned mice. AB - Previously we have shown that a group of patients treated for iron overdose with prolonged deferoxamine (DFO) infusion died of adult respiratory distress syndrome (ARDS). We now describe a model to investigate the mechanism of this pulmonary toxicity. Mice treated with 1 oral dose of iron (Fe) and then multiple injections of DFO, or with the chelated product ferrioxamine alone, did not develop lung lesions, even at doses which induced mortality. To potentiate any possible free radical reaction, other groups of mice were treated similarly while exposed to 75 80% O2 over a 4-day period. Ten of 12 mice receiving 0.75 mg Fe and then DFO (10 mg, 4 times/day for 4 days) with hyperoxia died suddenly. At autopsy the lungs were dark red and solid; sections showed hyaline membranes and alveolar exudates of edema, fibrin, and PMN. Electron microscopy showed massive destruction of the alveolar epithelium; using cerium chloride, a free radical reaction product was demonstrated at the alveolar surface. Lung lavage fluid contained 10-12 x normal levels of protein when the Fe-DFO-O2 group was compared to air or O2 controls. Mice receiving DFO or Fe, plus O2, showed only slight injury and a small increase in alveolar protein. The results indicate that Fe plus DFO generates free radicals in the lung, a reaction potentiated by hyperoxia to produce an ARDS-like picture. This suggests that the pulmonary toxicity of DFO in iron-poisoned patients is due to its prooxidant activity resulting in free radical destruction of the airblood barrier. PMID- 8511776 TI - A mechanistic model of effects of dioxin on gene expression in the rat liver. AB - Improved methods for estimating the shape of the response curve for effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are needed in order to evaluate possible adverse health effects of TCDD. A mathematical model has been constructed to describe TCDD-mediated alterations in hepatic proteins in the rat. In this model it was assumed that TCDD mediates increases in the liver concentration of transforming growth factor-alpha (TGF-alpha) by a mechanism which requires the aryl hydrocarbon (Ah) receptor. TGF-alpha subsequently binds to the epidermal growth factor (EGF) receptor, a process which is known to cause internalization of this receptor in hepatocytes. This action is thought to be an early event in the generation of a mitogenic signal. Because TCDD decreases binding of EGF in the livers of intact female rats but not in ovariectomized rats, this effect was further assumed to be dependent on estrogen action. The model postulates Ah receptor-dependent effects on the concentration of cytochrome P450 1A2 (CYP1A2), which is involved in the metabolism of estradiol, and on the concentration of the estrogen receptor. The model also incorporates information on induction of cytochrome P450 1A1 (CYP1A1) by TCDD. The biochemical response curves for all these proteins were hyperbolic (Hill exponents in the equations for their expression were found to be 1), indicating a proportional relationship between target tissue dose and protein concentration at low administered doses of TCDD. The model successfully reproduced the observed tissue distribution of TCDD, the concentrations of CYP1A1 and CYP1A2, and the effects of TCDD on the Ah, estrogen, and EGF receptors over a wide dose range. PMID- 8511777 TI - Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P450-mediated acute cell injury in cultured rat hepatocytes. AB - In a few patients diclofenac produces mild increases in serum aminotransferase activity and in rare cases may be associated with the occurrence of fulminant hepatic necrosis. Both direct toxic effects of a diclofenac metabolite and hypersensitivity reactions have been suggested as possible molecular mechanisms of liver injury. We investigated the pathways of bioactivation and cytotoxicity of diclofenac, which undergoes both aromatic hydroxylation and acyl glucuronidation, in short-term cultured rat hepatocytes. LDH release was first evident after 4 hr of incubation with diclofenac (> 500 microM). In addition, time- and concentration-dependent covalent binding of [14C]diclofenac to hepatocellular proteins occurred, indicating the presence of a reactive intermediate. To specifically explore the role of the acyl glucuronidation pathway in the induction of cytotoxicity and covalent drug-protein adducts, we used two inhibitors of the UDP-glucuronosyltransferase (UDPGT), borneol and 7,7,7 triphenylheptyl-UDP. LDH release was markedly increased in the presence of either UDPGT inhibitor. Alternatively, covalent binding to hepatocellular proteins was greatly reduced when the glucuronide formation was selectively blocked. Furthermore, in vitro inhibition of P450-dependent oxidative biotransformation with the selective inhibitor of the CYP2C subfamily sulfaphenazole or with cimetidine markedly reduced the extent of cytotoxicity, whereas the degree of covalent adduct formation remained unchanged. Similarly, pretreatment of the rats with phenobarbital (80 mg/kg/day for 4 days) delayed the onset and reduced the extent of diclofenac-induced LDH release. Collectively, these results indicate that the formation of a toxic diclofenac metabolite(s) catalyzed by P4502C in hepatocytes leads to acute lethal cell injury, whereas diclofenac acyl glucuronide formation is associated with covalent binding of a reactive metabolite to hepatocellular proteins that is not related to the acute cytotoxicity. The protein adduct formation and its modulation by UDPGT may, however, be toxicologically relevant for the expression of diclofenac hepatitis. PMID- 8511778 TI - A possible mechanism for the formation of 14CO2 via 2-methoxyacetic acid in mice exposed to 14C-labeled 2-methoxyethanol. AB - Small amounts (6-12%) of radioactivity administered by gavage as 14C-labeled 2 methoxyethanol (2-ME) or 2-methoxyacetic acid (2-MAA) to pregnant mice are exhaled as 14CO2 as well as accumulated in tissues that are highly active in the synthesis of macromolecules (Sleet et al., Toxicol. Appl. Pharmacol. 84, 25-35, 1986; Mebus et al., Toxicol. Appl. Pharmacol. 112, 87-94, 1992). In addition, pregnant CD-1 mice similarly administered 13C-labeled 2-ME excrete urinary metabolites that may arise from incorporation of a coenzyme A thioester of 2-MAA into the Krebs cycle, forming methoxycitrate (Sumner et al., Chem. Res. Toxicol. 5, 553-560, 1992). Based on these previously published observations, we propose a mechanism for the further metabolism of methoxycitrate that is consistent with the detection of 14CO2 after administering either [1-14C]2-MAA, [2-14C]2-ME, or [methoxy-14C]2-ME to mice. This postulated pathway may also explain the tissue specific accumulation of radioactivity arising from [14C]2-ME. PMID- 8511779 TI - The effect of glutathione depletion on methyl mercury-induced microtubule disassembly in cultured embryonal carcinoma cells. AB - Microtubule (MT) assembly and stability are thought to be dependent on intracellular glutathione for the maintenance of critical sulfhydryl groups. Since methyl mercury (MeHg) is a sulfhydryl-binding toxicant, it is possible that alteration of intracellular glutathione status might enhance the toxic effects of MeHg on microtubules. The influence of MeHg on the relationship between intracellular glutathione and the structural integrity of interphase microtubules was assessed in embryonal carcinoma cells by immunofluorescence microscopy, using antibodies to tyrosinated and acetylated alpha-tubulins. Intracellular glutathione concentrations were reduced by treatment with 10 microM buthionine sulfoximine (BSO; an inhibitor of gamma-glutamyl cysteine synthetase) for 18-24 hr. BSO-treated cells displayed little change in the pattern of microtubule staining, despite reduction of glutathione levels to less than 10% of control levels. Similarly, a combination of BSO and the nonspecific glutathione-depleting agent diethylmaleimide (DEM) had little effect on microtubule networks, except at the highest concentrations of DEM where nonspecific cytotoxicity was observed. The susceptibility of microtubules to MeHg-induced disassembly was determined in normal and glutathione-depleted cells incubated with 1.0 to 7.5 microM MeHg for 2 hr. MeHg treatment alone resulted in concentration-dependent disassembly of microtubules; depletion of glutathione with BSO prior to MeHg treatment did not enhance MT damage. Further, BSO-pretreated cells exposed to MeHg still showed substantial recovery of microtubule networks following removal of MeHg from culture media, even when glutathione levels remained less than 5% of control levels. These data indicate that the integrity of interphase microtubules is largely unaffected by reductions in glutathione concentration and that susceptibility of microtubules to MeHg-induced disassembly is not directly dependent on intracellular glutathione content. PMID- 8511780 TI - Nickel induces increased oxidants in intact cultured mammalian cells as detected by dichlorofluorescein fluorescence. AB - Exposure of intact cultured Chinese hamster ovary (CHO) cells to water-soluble nickel (Ni) salts and to relatively water-insoluble crystalline nickel subsulfide (Ni3S2) resulted in an increased formation of the fluorescent oxidized compound, dichlorofluorescein (DCF) from the parent nonfluorescent compound, 2,7 dichlorofluorescin diacetate. This fluorescent product was also formed in vitro following oxidation with relatively strong oxidants such as hydrogen peroxide in the presence of peroxidase, suggesting that Ni increased the concentration of hydrogen peroxide in intact cells. However, formation of other strong oxidants such as hydroperoxides is possible since they have also been shown to cause the oxidation of the nonfluorescent dichlorofluorescin to the fluorescent product DCF in vitro. Localization of the oxidized fluorescent DCF in intact cells was also examined by fluorescence microscopy. Both Ni3S2 and NiCl2 appeared to increase the degree of fluorescence in intact CHO cells around the nuclear membranes. This increase in fluorescence was greater in the presence of relatively water insoluble Ni3S2 than water-soluble NiCl2. These results add to the emerging concept that Ni-induced genotoxicity may be mediated by oxygen radical intermediates. PMID- 8511781 TI - Oxyradical generation from leukocytes during endotoxin-induced microcirculatory disturbance in rat mesentery--attenuating effect of cetraxate. AB - By using the intravital microscope equipped with digital imaging processor, we investigated the granulocyte-mediated oxidative burst during the endotoxin induced microvascular derangement in rat mesentery. The leukocyte behavior after the injection of acridine orange was detected by using a silicon-intensified target camera, the erythrocyte velocity was measured by using a high-speed video camera system, and the luminol-dependent photoemission was visualized by an ultrasensitive photon-counting camera in lipopolysaccharide (LPS)-treated microvascular beds. At 60 min after the LPS administration, a significant leakage of FITC-labeled albumin was observed along mesenteric venules under a fluorescence microscopy. The number of sticking leukocytes increased in association with the decrease in erythrocyte velocity after starting the LPS infusion. The luminol-dependent chemiluminescence in microvascular beds gradually increased over that recorded prior to LPS exposure and was fourfold higher 60 min after the start of LPS infusion. The distribution of the photoemission clearly corresponded to the venular endothelium, to which leukocytes adhered. In blood samples taken from the mesenteric vein at 60 min after the LPS administration, a decrease in the number of granulocytes and increases of total and individual chemiluminescence activities were observed. These results suggest that LPS induces oxidative burst from granulocytes on the venular endothelium. Cetraxate, an inhibitor of proteases including plasmin, significantly inhibited the leukocyte activation and prevented alterations in microvascular hemodynamics induced by LPS in vivo, whereas it had no effect on the LPS-induced oxyradical generation from adherent leukocytes in vitro. The present study demonstrates that proteases such as plasmin may play an important role in the pathogenesis of endotoxin-induced microvascular disturbances. PMID- 8511782 TI - Determination of hemoglobin adducts in humans occupationally exposed to acrylamide. AB - Hemoglobin (Hb) adduct determinations were used to monitor occupational exposure to acrylamide (AA) and acrylonitrile (AN). Forty-one workers in a factory in the People's Republic of China who were involved in the synthesis of AA by catalytic hydration of AN and the manufacturing of polyacrylamides were studied. Ten nonexposed workers in the same city served as controls. AA and AN exposures were monitored using the modified Edman degradation procedure for the determination of their respective Hb adducts to N-terminal valine. The adduct levels in the exposed workers were 0.3-34 nmol/g Hb for AA and 0.02-66 nmol/g Hb for AN, as determined by gas chromatography-mass spectrometry (GC-MS). The formation of glycidamide (GA), the epoxide metabolite of AA, in humans was demonstrated by GC MS analysis of its Hb adduct to N-terminal valine following acid hydrolysis, ion exchange chromatography, and derivatization. The GA adduct was detected in samples from the exposed persons with levels of 1.6-32 nmol/g Hb. There was a linear relationship between the AA and GA adduct levels (r = 0.96) and the ratio of the in vivo doses of GA and AA was 3:10. These results suggest that AA is metabolized to GA in humans, as had previously been shown in the rat. The high AA adduct levels in the exposed workers, as compared to those expected from air concentrations, indicate that dermal exposure may contribute significantly to the total uptake of AA. The average daily in vivo doses of AA and GA in the highest exposed workers were comparable to the in vivo doses in rats injected with 3 mg/kg AA. Since a regimen of 2 mg/kg/day is known to cause a significant increase of tumors in rats, preventive measures may be necessary for humans exposed to high levels of AA in industrial settings. PMID- 8511783 TI - Glutathione oxidation and embryotoxicity elicited by diamide in the developing rat conceptus in vitro. AB - This study was performed in the rat whole-embryo culture system to investigate the effects of glutathione oxidation by diamide, a thiol oxidant, in developing rat conceptuses during early organogenesis. The effects of diamide on reduced glutathione (GSH), glutathione disulfide (GSSG), and embryotoxicity were found to be concentration and time dependent. Diamide at concentrations of 75 and 100 microM produced abnormal axial rotation (62-89%), decreased viability (to 69% by 100 microM diamide), and reduced protein and DNA content in the embryo and visceral yolk sac (VYS) when evaluated on Day 11. High concentrations of diamide (250-500 microM) resulted in 100% mortality. GSH and GSSG levels in the conceptuses were not significantly affected during 2 hr following diamide addition at concentrations of 50 to 100 microM. At concentrations of 250 and 500 microM, rapid GSH depletion (50% of control) was seen within 5 min of exposure and was followed at 5-30 min by a significant increase in GSSG relative to control values. Diamide (500 microM) exposure for only 15 min on Gestational Day 10 was sufficient to elicit malformations (53% of exposed conceptuses with abnormal axial rotation) without significant loss of viability. After 30 min of exposure to the high concentration (500 microM), viability was decreased to 71% and defects of axial rotation increased to 87% in surviving conceptuses. This indicates that events associated with initial exposure are critical for expression of toxicity. Inhibition of glutathione disulfide reductase (GSSG reductase) activities in embryo and VYS with 1,3-bis(2-chloroethyl)-1-nitro sourea prior to diamide addition potentiated the embryotoxicity of diamide (75 microM) and resulted in corresponding reductions in GSH/GSSG ratios as determined during the first 2 hr of exposure. Inhibition of new GSH synthesis with L buthionine-[S,R]-sulfoximine during diamide (75 microM) exposure also exacerbated toxicity compared to diamide treatment alone. These results implicate the involvement of GSH synthesis and GSSG reductase activity in mediating the embryotoxicity of diamide. PMID- 8511784 TI - Essential fatty acid deficiency in cultured human keratinocytes attenuates toxicity due to lipid peroxidation. AB - Human keratinocytes are commonly grown in culture with a serum-free medium. Under these conditions, keratinocytes become essential fatty acid deficient (EFAD), as determined by gas chromatographic analysis of cell phospholipid fatty acid composition. Exposure of EFAD keratinocytes for 2 hr to concentrations of t-butyl hydroperoxide (tBHP) up to 2 mM did not result in toxicity assessed by lactate dehydrogenase (LDH) release and only a small indication of lipid peroxidation assessed by the release of thiobarbituric acid-reactive substances (TBARS). Addition of 10 microM linoleic acid (LA) to serum-free medium alleviated the EFAD condition by increasing the phospholipid content of LA and its elongation and desaturation products, arachidonic acid and docosatetraenoic acid. Exposure of LA supplemented keratinocytes to tBHP resulted in significant LDH (at 1 and 2 mM tBHP) and TBARS (tBHP concentration dependent) release. TBARS release was also significantly elevated in unexposed LA-supplemented keratinocytes (basal release). Co-supplementation with the antioxidant, alpha-tocopherol succinate (TS) prevented tBHP (1 mM)-induced LDH release in LA-supplemented cultures. TS supplementation also attenuated the effect of tBHP on TBARS release, but when compared to TS-supplemented EFAD cultures, LA supplementation still led to increased tBHP-induced TBARS release. Keratinocyte cultures are potentially useful as an alternative to animals in toxicology research and testing. It is important, however, that the cell model provide a response to toxic insult similar to that experienced in vivo. Our results suggest that fatty acid and antioxidant nutrition of cultured keratinocytes are important parameters in mediating the toxic effects of lipid peroxidation. PMID- 8511785 TI - Inorganic mercury absorption in mature and immature rat jejunum: transcellular and intercellular pathways in vivo and in everted sacs. AB - The objective of the present work was to test the hypothesis that toxic and nonessential heavy metals in general, and inorganic Hg in particular, are taken up in rat jejunum by a mechanism similar to that previously proposed for Cd. The initiating step in Cd absorption involves electrostatic interaction of the cation with negative membrane charges. In contrast, Hg appears to react with apical membranes as an anion, although overall uptake is not inhibited by the stilbene inhibitor of anion transport DIDS. Further, the ratio of Cd/Hg uptake falls along the jejunum. However, several similarities between Cd and Hg uptakes were observed. Neither process depends on reactive sulfhydryl groups or on oxidative metabolism. Although tissue Hg, unlike Cd, could not be rigorously separated into membrane-bound and intracellular compartments, uptake of both metals includes their relatively temperature-insensitive and rapid influx into a pool readily accessible to suitable extracellular chelators. Another more temperature sensitive and slower component leads to the filling of a relatively chelation resistant compartment, identified in the case of Cd as intracellular. Non specific membrane properties such as surface charge and perhaps membrane fluidity can thus account for mucosal Cd and Hg uptakes; no contribution of specific transport systems need be postulated. Mucosal permeability, calculated in reference to ethanol uptake as measure of absorbing surface area, falls to the same extent for Cd and Hg during postweaning development. Because this fall, however, parallels a diminution in polar diffusion pathways, the mechanism of the faster metal absorption in weanlings may have little bearing on the slower transcellular process in adults. Incidentally, polar diffusion pathways increase in mature jejunum upon preparation of everted sacs, a further limitation on the usefulness of this preparation for the quantitative study of normal intestinal solute transport. PMID- 8511787 TI - Apparent rates of glutathione turnover in rat tissues. AB - Apparent first-order rate constants for glutathione (GSH) turnover were determined for 14 tissues in male Fischer 344 rats after intravenous injection of [35S]cysteine ([35S]Cys). Rate constants for glutathione turnover were estimated by nonlinear least-squares iterative minimization from the decrease in GSH specific activity 1-102 hr after administration of [35S]Cys. Tissue nonprotein sulfhydryl concentrations were determined by Ellman's assay and compared with GSH and Cys levels detected by high-performance liquid chromatography equipped with an electrochemical detector. Additionally, total radiolabeled [35S]GSH was determined by high-performance liquid chromatography equipped with a flow-through radioactivity detector. There were substantial differences in the apparent rates of GSH turnover between the various tissues examined. For example, both the liver and the kidney had rapid turnover rates with half-lives of 1-5 hr, while those for heart, skeletal muscle, and blood were much slower with half-lives of 68-118 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach = caecum > duodenum = small intestine = large intestine > colon > forestomach. [35S]GSH had a half-life in lung and skin of approximately 63 and 50 hr, respectively. PMID- 8511786 TI - Free radicals in toxicology. AB - Free radicals are recognized more and more frequently as being involved in the mechanism of toxicity of chemicals. In some cases, the organic radicals are involved, but often oxygen radicals result from redox cycling chemicals. Free radicals are usually very reactive, which, in addition to causing toxicities, can make them difficult to detect. Electron spin resonance (ESR) techniques are frequently used, but generally the radicals must be trapped to form a more stable radical for detection. Quantitation is therefore often very difficult. Free radicals of many xenobiotics are formed during their metabolism by enzymes such as cytochrome P450 or peroxidases. In some cases, chemicals can redox cycle using reductases, such as cytochrome P450 reductase, which can catalyze one-electron reductions. Some redox cycling xenobiotics reduce molecular oxygen by one electron to generate superoxide. Superoxide can cause toxicities against which superoxide dismutase is protective. However, in the presence of transition metals such as iron, superoxide can generate the very reactive hydroxyl radical by the iron-catalyzed Haber-Weiss reaction. Iron is therefore normally tightly controlled by transport and storage proteins. Chemicals that can release iron from these proteins can be very toxic, causing lipid, protein, and nucleic acid oxidation. The oxidation of these species, such as a low-density lipoprotein, is generally protected by a complex antioxidant system involving glutathione and glutathione peroxidase, vitamin E, ascorbic acid, etc. PMID- 8511788 TI - In vitro organotin administration alters guinea pig cochlear outer hair cell shape and viability. AB - Trimethyltin (TMT) and triethyltin (TET) disrupt auditory function at doses far below those shown to be neurotoxic. In vivo studies suggest that the initial effect of TMT on hearing occurs at the inner hair cell/spiral ganglion cell synapse, while later, the outer hair cell (OHC) undergoes structural and functional damage. TET produces acute effects upon afferent neurotransmission similar to those observed following TMT, but TET's effects on OHC structure and function have not been examined. OHCs are motile elements within the cochlea, believed to modulate the sensitivity and tuning within the inner ear. Changes in OHC length may alter hearing function, and length changes have been reported following exposure to various ototoxic agents in vitro. In the present study, 77 OHCs from 45 pigmented male guinea pigs were isolated in primary culture and exposed for 90 min to concentrations between 30 microM and 1.0 mM of TMT or TET and then to bathing medium for 30 min to remove the toxicant. Significant shortening of the OHC cell body occurred at all doses to both organotins, with a mean reduction in length of 15.1 and 20.2% for 1.0 mM TMT and TET, respectively, at the end of testing; control cells were only 3.4% shorter at the end of 90 min of perfusion with bathing medium. The effect of organotin exposure on OHC volume was not consistently related to either TMT or TET concentration or altered cell length. In addition, disruption of the plasma membrane characterized by bleb formation, the forceful ejection of cytoplasm, or bursting was seen in 80% of cells exposed to 1.0 mM TET, although not TMT; lower concentrations of both organotins disrupted the cell membrane in 10-30% of cells. Membrane rupture was not reliably associated with either increased cell volume or decreased length, implicating a weakening of the plasma membrane or cortical lattice as the basis for this effect. Consistent with the irreversible structural weakening of the lateral wall, resorption of organotin-induced cytoplasmic blebs was never evidenced. Qualitatively, subcellular elements in the central core of many organotin-treated OHCs appeared pathological. These changes are similar to histopathological changes observed following in vivo organotin administration and may represent one target of acute alkyltin ototoxicity. PMID- 8511789 TI - Disruption by methylmercury of membrane excitability and synaptic transmission of CA1 neurons in hippocampal slices of the rat. AB - In order to examine the effects of methylmercury (MeHg) on central synaptic transmission, field potentials were recorded in the CA1 neurons of hippocampal slices by using extracellular microelectrode recording techniques. After stimulation of Schaffer collaterals at low frequency (0.25 Hz), population spikes and excitatory postsynaptic potentials (EPSPs) were recorded at the cell bodies and apical dendrites of CA1 pyramidal cells, respectively. Antidromically activated population spikes were also recorded at the cell bodies of CA1 pyramidal cells by stimulating the alveus. Long-term potentiation (LTP) was induced by application of brief high-frequency stimulation (15 trains of four stimuli per train at 100 Hz) after 25 min of population spike baseline recordings. MeHg was applied to slices acutely by bath perfusion with artificial cerebrospinal fluid (ACSF). At 20-500 microM, MeHg significantly increased and then decreased the amplitudes of, or blocked, the population spikes, EPSPs, and antidromically activated population spikes. Time to increase and time to block of these field potentials were concentration-dependent. Exposure of slices to 4 microM MeHg for 180 min increased but did not reduce the amplitudes of population spikes, EPSPs, or antidromically activated population spikes. The effects of MeHg on population spikes induced by either orthodromic or antidromic stimulation were similar. In the absence of MeHg, application of high-frequency stimulation increased population spike amplitudes by 60-100%. This effect (LTP) could be sustained for more than 2 hr in the absence of MeHg. When 100 microM MeHg was applied concomitantly with high-frequency stimulation, the population spike amplitudes were increased by an additional 20-50% based on the already elevated population spike amplitude by high-frequency stimulation. Subsequently, population spike amplitudes were reduced and finally blocked in a manner similar to the effect of MeHg on population spikes recorded without high-frequency stimulation. Application of MeHg (100 microM) for 20 min prior to high-frequency stimulation did not prevent induction of LTP even though the population spike amplitudes had been decreased by more than 10% of the control level, suggesting that MeHg may not alter induction of LTP. Reversibility of the effects of MeHg was examined by washing slices with MeHg-free ACSF or 1 mM D-penicillamine for 60 120 min after MeHg treatment. Washing slices with MeHg-free ACSF caused at best partial reversal of effects of MeHg. D-Penicillamine, a chelator of MeHg, completely reversed the effects of MeHg on EPSPs but only partially reversed the effects of MeHg on population spikes, antidromically activated population spikes, and LTP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8511790 TI - Impaired regulation of surfactant phospholipid metabolism in the isolated rat lung after nitrogen dioxide inhalation. AB - Various drugs have been shown to stimulate surfactant phospholipid metabolism. Particularly beta-adrenergic agonists play an important role under physiologic conditions. For the first time we have studied whether nitrogen dioxide (NO2) inhalation alters beta-adrenergic regulation of surfactant phospholipid metabolism in the model of the isolated lung. Rats were continuously exposed in vivo to a 5 ppm NO2-containing atmosphere for 48 hr. The lungs were isolated and perfused in presence of the beta-adrenergic agonist dopexamine and surfactant metabolism was studied in three lung compartments: (1) lung lavage, (2) lung tissue, and (3) lavagable free alveolar cells. We found that (1) in normal rat lungs dopexamine increased the incorporation of palmitate and choline from the perfusate into lung lavage phospholipids. In nitrogen dioxide exposed rat lungs beta-adrenergic stimulation did not cause an increase in precursor incorporation. No significant difference in unstimulated precursor incorporation was found for normal and NO2-exposed rat lungs. (2) Lung tissue from rats exposed to NO2 showed a decreased precursor incorporation into disaturated phosphatidylcholine due to an augmented cellular pool size. (3) Lavagable alveolar cells showed an increased palmitate uptake after nitrogen dioxide inhalation and by beta-adrenergic stimulation. From these data we conclude that nitrogen dioxide inhalation impairs the beta-adrenergic regulation of surfactant phospholipid metabolism. Moreover these data underline the importance of beta-adrenergic agonists in surfactant metabolism. PMID- 8511791 TI - Uptake of two zwitterionic surfactants into human skin in vivo. AB - To evaluate the potential risk associated with dermal exposure to nitrogen containing amphiphiles commonly found in household and personal-care products, the uptake of N,N-dimethyl-N-dodecylglycine (dodecylbetaine, C12BET) and N,N dimethyl-N-hexadecylglycine (hexadecylbetaine, C16BET) into human skin in vivo has been measured. The 14C-radiolabeled chemicals were applied in aqueous solution (C12BET concentrations 16, 100, and 800 mM; C16BET concentrations 0.14, 1.0, and 5.4 mM) to the dorsal upper arms of male volunteers for 30 min. At the end of this exposure period, the remaining applied solution was removed, the skin surface was thoroughly washed, and the stratum corneum at the administration site was removed by repeated tape-stripping. Dermal uptake was assessed (i) by direct measurement of the radioactivity recovered on the tape-strips, and (ii) from a predictive relationship previously derived from other research using a similar protocol. As expected, agreement between the two approaches was reasonable (generally within a factor of 3-4); the predictive relationship attempts to account for penetrant which cannot be recovered by the tape-stripping process, and anticipates, therefore, greater chemical exposure to the body than that expected on the basis of the tape-strip associated material alone. A positive control, using the previously studied penetrant, caffeine, demonstrated that the experimental procedure was conducted appropriately. Absorption of the betaines into human skin was significant (for C12BET, uptake was 28-160 nmol/cm2; that for C16BET was 2.3-19.5 nmol/cm2) and was primarily localized (as was caffeine) in the outer layers of the stratum corneum. In parallel experiments, in which unlabeled betaines were applied for 30 min, instead of tape-stripping, skin barrier function (measured by transepidermal water loss) was assessed. No betaine induced effects on the stratum corneum were observed (in contrast to the sometimes large perturbations seen in vitro following considerably longer exposure times). Overall, the results indicated that the use of these betaines in personal care products, when intended for limited use and rinse-off application, gives no reason for safety concerns. PMID- 8511792 TI - Effect of cadmium on bone calcium and 45Ca in nonpregnant mice on a calcium deficient diet: evidence of direct effect of cadmium on bone. AB - To clarify the mechanism of the effect of Cd on bone, virgin female mice with 45Ca prelabeled skeletons (15 microCi/mouse) were exposed to a Ca-deficient diet (0.002%) containing 0, 5, or 25 ppm Cd or 25 ppm Pb for 32 days. During the first 72 hr, the 0 ppm controls showed a 2.5-fold decrease in fecal 45Ca excretion (decreased bone resorption), a 12-fold decrease in total fecal stable Ca, a 5 fold decrease in endogenous fecal Ca excretion, and a significant elevation in both serum 45Ca (108%) and specific activity (92%) due to the Ca-deficient diet. In contrast, Cd immediately and significantly increased fecal 45Ca excretion (55%), total fecal stable Ca (13%), endogenous fecal Ca excretion (32%), as well as serum 45Ca (15%) and specific activity (17%) (25 ppm Cd vs 0 ppm), supporting the hypothesis of an early, direct effect of Cd on bone. Overall, during 32 days, Cd at 25 ppm induced a 60% increase in fecal 45Ca excretion compared to 0 ppm controls, providing a sensitive measure of the Cd-induced increase in bone resorption. In contrast, the effect of Cd was too small to cause a statistically significant 45Ca loss from the right femur and lumbar vertebrae, but a significant 45Ca loss (up to -13%) was seen for the remaining skeleton (25 ppm vs 0 ppm group). In addition, Cd at 25 ppm induced small but statistically significant decreases in ash weight (-12%), ash weight to dry weight (-5%), Ca/dry (-7%), and Ca/ash (-2%) in the right femur and significant decreases in ash/dry (-7%) and Ca/dry (-12%) in the lumbar vertebrae compared with the controls. Our present study supports the hypothesis that Cd at 25 ppm had a significant direct effect on bone, with no effect at 5 ppm Cd or 25 ppm Pb, and no appearance of the extreme demineralization characteristic of Itai-Itai disease, although mice were exposed to a Ca-deficient diet for 32 days. Our results from this and earlier studies support the view that chronic Cd exposure along with nutritional deficiency contributed to the pathogenesis of Itai-Itai disease among multiparous, postmenopausal women in Japan. PMID- 8511793 TI - Differential cytotoxic sensitivity in mouse and human cell lines exposed to organophosphate insecticides. AB - Neuroblastoma cell lines were used to examine the differential interspecies response (i.e., species selectivity) to organophosphates (OPs). Baseline activities of the major target esterases, i.e., cholinesterase, carboxylesterase, and neurotoxic esterase, were assayed in mouse and several human neural candidate cell lines. These activities were found to be variable within individual cell lines and among the various tested cell lines. Cytotoxicity data using the neutral red fluorometric assay were collected on both human (SH-SY5Y) and mouse (NB41A3) neuroblastoma clones exposed to a variety of OP insecticides. IC50 data indicated that the tested mouse cell line was consistently more sensitive than the human cell line to equimolar doses of various OP compounds (e.g., mipafox, parathion, paraoxon, DFP, leptophos oxon, fenthion, and fenitrothion). This difference in cytotoxic sensitivity was most pronounced in response to compounds requiring metabolic bioactivation (i.e., protoxicants). Cytotoxicity data also demonstrated that the NB41A3 mouse neuroblastoma cell line was more metabolically competent than the SH-SY5Y human cell line in converting the protoxicant parathion to its neurotoxic metabolite, paraoxon. B-lymphoblastoids, genetically engineered with human P450 cDNAs, demonstrated higher cytotoxic sensitivity to parathion than unengineered cells, indicating that cytochrome P450-associated monooxidase activity could also influence cytotoxic sensitivity to parathion in culture. These data suggest that interspecies-selectivity in response to OP related cytotoxicity is influenced by intercellular differences in metabolism and baseline esterase activities. PMID- 8511794 TI - Glutathione biosynthesis in the postimplantation rat conceptus in vitro. AB - Glutathione (GSH) biosynthesis in Day 10 rat conceptuses was characterized in whole embryo culture by evaluation of net rates of GSH replenishment in whole conceptuses, embryos, and visceral yolk sacs (VYS); uptake and distribution of [35S]cysteine and [35S]methionine from the culture medium; incorporation of 35S labeled amino acids into GSH; and efflux of [35S]GSH into the culture medium. Diethyl maleate (DEM, 500 microM) depleted intracellular GSH pools in embryo and VYS to 30% of control values within 45 min. Restoration of GSH pools in VYS began immediately and continued at a rate of 295 pmol/conceptus/hr until GSH concentrations exceeded initial control levels at 4 hr. GSH pools in the embryo remained depleted for over 2 hr, followed by resynthesis at initial rates of 118 pmol/conceptus/hr. [35S]Cysteine (0.2 mM) uptake from the culture medium resulted in whole conceptus accumulations that reached 1.6 nmol/conceptus. The portion of intracellular free cysteine obtained through uptake of extraconceptal amino acid was 40-90 pmol/conceptus and represented less than 20% of the total free intracellular cysteine. [35S]Methionine (0.2 mM) accumulation surpassed that of cysteine at all time points by two- to threefold. [35S]Cysteine, added 2 hr after DEM, was incorporated into GSH at rates of 126 pmol/conceptus/hr during the first hour. By 4 hr, rates of incorporation had declined to 22 pmol/conceptus/hr. L Buthionine-[S,R]-sulfoximine (1 mM) completely eliminated incorporation of [35S]cysteine into GSH. Net efflux of [35S]GSH into the culture medium accounted for less than 40 pmol of total GSH when measured 5 hr after DEM addition. Although effectively transported into the conceptus and readily utilized in protein synthesis, 35S from methionine was not incorporated into GSH under any conditions tested. After chemical depletion, de novo GSH synthesis occurs exclusively in the VYS. Embryonic recovery begins only after GSH pools in the VYS are replete. Prolonged embryonic GSH depletion and slower recovery rates indicate that the embryo may be selectively susceptible to chemical insult following depletion of GSH. PMID- 8511796 TI - Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. AB - The present study was undertaken to investigate the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in vivo in the male Sprague Dawley rat by physiologically based toxicokinetic (PBTK) modeling. First, the metabolic constants (Vmax and Km) were determined for TOL and XYL individually by conducting a series of closed-chamber inhalation exposures of three rats to starting concentrations of 500 to 4000 ppm. The values of Km (TOL, 0.55 mg/liter; XYL, 0.20 mg/liter) and Vmax (TOL, 4.8 mg/hr/kg; XYL, 8.4 mg/hr/kg) were obtained following best visual fit of PBTK model simulations to experimental data. Then using the same experimental set-up, rats were exposed to three different mixtures of both solvents (500 ppm TOL + 1000 ppm XYL; 1000 ppm TOL + 1000 ppm XYL; 1000 ppm TOL + 500 ppm XYL). The data from the time course of chamber solvent concentrations were analyzed with a binary chemical mixture PBTK model that had four mechanistic hypotheses of metabolic interaction (i.e., no interaction, competitive inhibition, noncompetitive inhibition, and uncompetitive inhibition) quantitatively defined in the liver compartment. The validity of the various model descriptions was verified with open-chamber inhalation exposure data on toxicokinetics of TOL and XYL. Overall, the results of this combined experimental and modeling approach are consistent with a competitive metabolic inhibition between XYL and TOL in the rat. PMID- 8511795 TI - The induction of cytochrome P4502E1 by nitrogen- and sulfur-containing heterocycles: expression and molecular regulation. AB - Several structurally related sulfur- and nitrogen-containing heterocycles including thiazole, pyrazine, pyridazine, pyrimidine, thiophene, and triazole, which are present in tobacco, tobacco smoke, and certain foods, have been employed with the goal of characterizing the effects of these agents on the inhibition and expression of P4502E1 in hepatic tissue and on the molecular level regulatory events governing enhanced expression. The results of this study reveal that whereas the binding constants of these compounds to 2E1 moderately correlated with the percentage inhibition of metabolic activity in vitro (r = 0.66), neither inhibition of metabolic activity nor binding to P4502E1 correlated with relative induction of P4502E1 levels (r = 0.07 and 0.03, respectively). Thiazole, which produced the greatest inhibition of metabolic activity (88%) and exhibited the highest binding affinity for P4502E1 (35 microM), induced P4502E1 approximately fourfold. In contrast, pyrazine and pyridazine, which only marginally inhibited metabolic activity (54 and 41%, respectively), and weakly bound 2E1 (73 and 384 microM, respectively), increased P4502E1 levels approximately four- and fivefold, respectively. A common feature associated with these inducers, however, was the substantial decrease in hepatic P4502E1 poly(A)+ RNA levels in treated animals relative to untreated animals. Slot and Northern blot hybridization analyses revealed an approximately 80% decrease in P4502E1 poly(A)+ RNA levels at 48 hr following treatment of rats with thiazole, and at 24 hr following treatment of animals with either pyrazine or pyridazine, relative to controls. P4502E1 poly(A)+ RNA levels appeared to increase gradually, returning to levels which approximated 60% of the P4502E1 poly(A)+ RNA levels present in untreated animals at 48 and 72 hr following treatment with pyrazine or pyridazine, respectively. The results of these experiments show that thiazole, pyrazine, and pyridazine induce P4502E1 in rats, that the induction of 2E1 is associated with a concomitant decrease in 2E1 poly(A)+ RNA levels, and that these agents differentially affect the expression of P4502E1. PMID- 8511797 TI - Effect of cadmium on osteogenesis within diffusion chambers by bone marrow cells: biochemical evidence of decreased bone formation capacity. AB - The biological and biochemical effects of cadmium administration on bone marrow in rats were examined. When young adult rats were administered cadmium (Cd) repeatedly at a dose of 750 micrograms/kg body wt for up to 4 weeks, metallothionein mRNA was detected by a gene expression analysis in their bone marrow at 2 weeks after the first Cd administration, though the amounts were lower than those in liver. To determine the direct effect of cadmium on bone formation, the potential of Cd-treated bone marrow cells and demineralized bone matrix (DBM) to form bone and cartilage was assessed using a diffusion chamber (DC) in vivo, by histological examination, and by biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus content, and the bone-specific vitamin K-dependent Gla-containing protein (BGP) content, relative to mineralization. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or nontreated rats (control) and were then implanted subcutaneously into syngeneic nontreated rats. The accumulation of BGP in DCs with Cd-treated bone marrow was significantly lower than that in control DCs. Unlike in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow; the ALP activity and calcium content in these implants were also significantly lower than those of the control bone marrow-containing chambers at the early stage of implantation. Histological examinations of chambers with Cd-treated marrow showed a decreased area of cartilage and bone foci compared with those in control chambers. These findings suggest that Cd administration inhibits the osteoblastic and chondroblastic differentiation pathway in bone marrow through direct effects on these cells. PMID- 8511798 TI - Effects of monocrotaline pyrrole on cultured rat pulmonary endothelium. AB - Administration of monocrotaline pyrrole (MCTP), a putative toxic metabolite of the pyrrolizidine alkaloid, monocrotaline (MCT), results in delayed and progressive pneumotoxicity in the rat. It has been suggested that the lung injury caused by this compound may be initiated by an interaction between MCTP and cells of the pulmonary vasculature. A likely site for initial binding of this reactive electrophile is the pulmonary endothelium. MCTP causes direct toxicity to cultured bovine and porcine pulmonary artery endothelial cells (BECs and PECs, respectively), but there exist species differences both in whole-animal response to the parent alkaloid and in cellular response to direct application of MCTP. In this study, the changes in cultured rat pulmonary vascular endothelial cells (RECs) after a single administration of MCTP were characterized in order to compare these with changes previously identified in this species in vivo. Studies with RECs have also provided an additional model for examination of species related differences in response to this toxicant. MCTP caused a delayed and progressive release of lactate dehydrogenase from REC monolayers. Progressive cell detachment was evident and remaining cells became enlarged, with morphologic changes comparable to those reported previously in BECs, including cytoplasmic vacuolization and nuclear enlargement. MCTP inhibited cell proliferation at concentrations of 0.05 micrograms MCTP/ml or greater, and DNA crosslinking was evident at 24 and 48 hr post-treatment. These results suggest that MCTP is directly toxic to cultured RECs, and the development of changes is reminiscent of that seen in the rat in vivo. The cytostatic nature of the compound, in combination with its cytolytic effect on RECs, could contribute to the development of pulmonary edema and other lung vascular changes seen in rats treated with MCT or MCTP. PMID- 8511799 TI - Dose-dependent urinary excretion of acrylonitrile metabolites by rats and mice. AB - The dose dependence of the urinary excretion of acrylonitrile (ACN) metabolites was studied after oral administration of [2,3-14C]ACN to male F-344 rats (0.09 to 28.8 mg/kg) and male B6C3F1 mice (0.09 to 10.0 mg/kg). Urine was the major route of excretion of ACN metabolites (77 to 104% of the dose), with less than 8% of the dose excreted in the feces. Reverse-phase HPLC analysis of urine from treated animals indicated five major components (1 through 5 in order of elution) that accounted for 75 to 100% of the total urinary radioactivity. Component 4 was observed in the urine of ACN-treated mice but was only present in trace amounts in the urine of ACN-treated rats. Components 1, 2, and 3 were present in the urine of animals administered [2,3-14C]cyanoethylene oxide (CEO), indicating that these components were derived from the epoxide metabolite of ACN. The ACN urinary metabolites were isolated by HPLC and identified by chromatographic and mass spectral analysis. Component 5 was N-acetyl-S-(2-cyanoethyl)cysteine and component 4 was S-(2-cyanoethyl)thioacetic acid, both derived from the glutathione (GSH) conjugate of ACN. Component 3 contained N-acetyl-S-(2 hydroxyethyl)cysteine, N-acetyl-S-(carboxymethyl)cysteine, and N-acetyl-S-(1 cyano-2-hydroxyethyl)cysteine. Component 2 was thiodiglycolic acid. These urinary metabolites are derived from catabolism of the GSH conjugates of CEO. The polar component 1 was not identified. These results demonstrate that GSH conjugation is the major disposition pathway of ACN. The excretion of metabolites derived from CEO was an approximately linear function of dose in both species, whereas the excretion of N-acetyl-S-(2-cyanoethyl)cysteine increased nonlinearly with dose. This nonlinearity indicates the presence of a saturable pathway competing with glutathione for ACN, most likely the cytochrome P450-dependent oxidation of ACN. Thiodiglycolic acid was formed 10-fold more in mice than in rats, but this species difference in the oxidative processing of GSH conjugates is probably not of toxicological significance. The ratio of ACN epoxidation to GSH conjugation was 0.50 in rats and 0.67 in mice. This species difference in ACN oxidation could have important toxicological implications, since CEO is believed to mediate the carcinogenic effects of ACN. PMID- 8511801 TI - Mobilization of hepatic cadmium in pregnant rats. AB - Mobilization of hepatic cadmium (Cd) in pregnant rats was investigated. Female Sprague-Dawley rats (200-250 g) were injected subcutaneously, daily with 1.0 mg Cd/kg body weight as CdCl2 for 8 days. A group of these rats was made pregnant. Copper (Cu), zinc (Zn), Cd, and metallothionein (MT) concentrations in the liver, kidney, and plasma of the control and Cd-injected, pregnant and nonpregnant rats, were compared. The hepatic Cd concentration of the Cd-injected rats decreased by 40% during pregnancy and became significantly lower than that of the nonpregnant Cd-injected rats. On the other hand, there was a concomitant increase (60%) of Cd concentrations in the kidney of the Cd-injected pregnant rats. MT in the Cd injected rats also showed a similar pattern of decrease in hepatic concentrations and increase in renal concentrations during pregnancy. Both Cd and MT contents in the placenta of the Cd-injected rats were higher than those of the control and there was a significant increase over the gestational period. Plasma Cd and MT concentrations of the Cd-injected pregnant rats were higher than those of Cd injected nonpregnant rats. These results suggest that pregnancy can mobilize the hepatic Cd which can be transferred to the kidney and placenta through the blood plasma. Moreover, the blood urea nitrogen levels of the pregnant Cd-injected rats were increased on Gestation Day 21 and 7 days after delivery, indicating signs of Cd nephropathy. The hepatic Cd, Cu, Zn, and MT concentrations of the newborn rats, however, were unaltered by Cd injections. Therefore, it is possible that pregnancy may induce a high risk of Cd nephrotoxicity in women with chronic Cd exposure. PMID- 8511800 TI - Regulation of phenobarbital-inducible cytochrome P450 2B1/2 mRNA by lovastatin and oxysterols in primary cultures of adult rat hepatocytes. AB - Lovastatin (LOVA) is a potent inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase widely used in clinical practice. We treated primary cultures of adult rat hepatocytes, maintained in a minimal, serum-free medium on Matrigel, a reconstituted basement membrane, with this drug, and found that the amounts of P450 2B2 mRNA detected on Northern blots were increased at the same doses (10(-5) to 3 x 10(-5) M) required for induction of HMG-CoA reductase mRNA, a gene known to be under oxysterol regulatory control. LOVA treatment produced selective effects increasing also the mRNA levels for P450s 2C6, 2C7, 3A1, and 4A1 but not for 1A1, 2A1/2, or NADPH-cytochrome P450 oxidoreductase. LOVA treatment increased the induction of 2B1/2 mRNA in cells cotreated with either phenobarbital (PB; 10( 4) M) or clotrimazole (CTZ; 10(-5) M), or of 3A1 mRNA in cells cotreated with PB (2 x 10(-3) M), but not dexamethasone (10(-5) M. LOVA treatment did not potentiate the induction of 1A1 or 4A1 mRNA in cells cotreated with beta naphthoflavone (10(-5) M) or ciprofibrate (10(-4) M), respectively. In contrast to the potentiation of 2B1/2 mRNA induction produced by treatments with LOVA in combination with PB or CTZ, cotreatment of hepatocytes with PB and CTZ did not result in increased induction relative to that seen in cells treated with either agent alone. Treatment of hepatocyte cultures with either mevalonate (3 x 10(-4) to 3 x 10(-3) M), the immediate product of HMG-CoA reductase, or 25 hydroxycholesterol (10(-6) to 10(-5) M), a model oxysterol, resulted in dose dependent suppression of 2B1/2 mRNA induction in cells treated with PB-like inducers. Taken together, our results demonstrate that LOVA is a unique inducer of P450 mRNA in cultured rat hepatocytes and implicate oxysterols as potential intracellular modulators of 2B1/2 induction. We conclude that endogenous metabolic factors including those related to cholesterol biosynthesis are critical in induction of liver cytochromes P450 2B1 and 2B2 by PB and "PB-like" agents. PMID- 8511802 TI - Effects of dose and routes of exposure on the disposition of 2,3,7,8 [3H]tetrabromodibenzo-p-dioxin (TBDD) in the rat. AB - Polybrominated dibenzo-p-dioxins and dibenzofurans are of major concern because of potential occupational and environmental exposures and their structural similarity to the highly toxic chlorinated analogues. 2,3,7,8-Tetrabromodibenzo-p dioxin (TBDD) is a closely related analogue in both structure and activity to the most toxic isomer 2,3,7,8-tetrachlorodibenzo-p-dioxin. The objectives of this study were to characterize the effects of dose and routes on absorption, excretion, and terminal tissue distribution of [3H]TBDD in the rat 72 hr after dosing. Rats were treated orally by gavage with 1, 10, 100, or 500 nmol/kg, intratracheally with 1 nmol/kg, or dermally with 1 nmol/kg (200 pmol/1.8 cm2). TBDD exhibited nonlinear oral absorption kinetics with maximum absorption (approximately 80%) occurring at dose < or = 10 nmol/kg, similar to the transpulmonary absorption. In contrast, dermal absorption of TBDD was low (approximately 12%). The major tissue depots of radioactivity were liver, adipose tissue, and skin. Tissue distribution of the oral dose was dose-dependent, with disproportionally greater hepatic concentrations occurring at absorbed doses of > 8 nmol/kg. Liver:adipose tissue (L:F) concentration ratios were 2.9 to 6.6 (lowest to highest oral dose, respectively). The lower L:F ratios observed for the dermal and intratracheal doses at 1 nmol/kg (1.5 and 2, respectively) were likely due to differences in absorbed dose and dose-related tissue distribution. Elimination of radioactivity in feces, the major route of excretion for all dose groups and routes, and urine was also nonlinear with respect to the oral dose. The results of the present study provide important considerations for high- to low-dose and route-to-route extrapolations with TBDD and other dioxins and furans in human risk assessments. PMID- 8511803 TI - Professional security notebook. Healing the workplace family--nurses leading the way. PMID- 8511804 TI - The contraceptive potential of breastfeeding in Bangladesh. AB - A consensus statement issued by the World Health Organization and the United Nations Children's Fund at the Bellagio conference in 1988 recommended that women begin practicing contraception six months after childbirth or when their menstrual cycle resumes, whichever occurs first. The question to be resolved is whether this approach, known as the Bellagio mixed-t strategy, should be adjusted to local patterns of lactational amenorrhea. Data from interviews with 4,580 Bangladeshi women with a currently open birth interval were analyzed with respect to the women's current status of breastfeeding, amenorrhea, contraception, and pregnancy. Pregnancies among breastfeeding, amenorrheic women occurred only beyond 12 months postpartum, while some menstruating women were observed to be pregnant from three months postpartum onward. The results of this study give evidence that the Bellagio recommendation can be best applied with country specific adjustments. Bangladesh, for example, could safely adopt a strategy with a 12-months' cutoff point. PMID- 8511806 TI - IUD protocols for international training. PMID- 8511805 TI - The dynamics of contraceptive use in Peru. AB - In 1986, the Demographic and Health Surveys project administered the first six year calendar history of events that included women's contraceptive use and their reasons for discontinuation in experimental surveys in Peru and the Dominican Republic. In this report the experimental survey from Peru is examined to demonstrate how the calendar data can be used to calculate multiple increment decrement life table rates of contraceptive discontinuation--including contraceptive failure, method switching, and abandonment of use--and of resumption of method use following discontinuation. These analyses reveal that nearly half of all Peruvian women who begin to use a method will stop using it within one year; 29 percent of women discontinue method use for nonpregnancy related reasons within one year of initiating use. Women who switch methods do so frequently, and many will return to a method used previously, or move on to a third method. Women who become pregnant after abandoning contraceptive use have similar contraceptive-use patterns to women who experience a contraceptive failure. PMID- 8511807 TI - Cameroon 1991: results from the Demographic and Health Survey. PMID- 8511808 TI - International human rights and women's reproductive health. AB - Neglect of women's reproductive health, perpetuated by law, is part of a larger, systematic discrimination against women. Laws obstruct women's access to reproductive health services. Laws protective of women's reproductive health are rarely or inadequately implemented. Moreover, few laws or policies facilitate women's reproductive health services. Epidemiological evidence and feminist legal methods provide insight into the law's neglect of women's reproductive health and expose long-held beliefs in the law's neutrality that harm women fundamentally. Empirical evidence can be used to evaluate how effectively laws are implemented and whether alternative legal approaches exist that would provide greater protection of individual rights. International human rights treaties, including those discussed in this article, are being applied increasingly to expose how laws that obstruct women's access to reproductive health services violate their basic rights. PMID- 8511810 TI - Malaria chemosuppression in pregnancy. II. Its effect on maternal haemoglobin levels, placental malaria and birth weight. AB - The malaria prophylactic effects of chloroquine (CQ), proguanil (PROG), and chloroquine-proguanil combination (CQ+PROG) during pregnancy on maternal haemoglobin levels (Hb), placental malaria, and birth weight were assessed in Muheza, Tanzania. Within 2 months of prophylaxis, severe anaemia in primigravidae (PG) was reduced from 21% (22 cases) to 13% (13 cases). There was no positive effect in multigravidae (MG). Sustained increases in the mean Hb occurred in PG of the PROG and CQ+PROG groups. The mean Hb of PG of the CQ group decreased after an initial increase, possibly due to the selection of more and highly chloroquine resistant strain(s). The mean birth weight of PG was highest in the CQ+PROG (2.89 kg) and least in the CQ group (2.71 kg). The CQ group had the highest low birth weight rate (LBW). The prevalence of placental malaria was highest in the CQ (28%) and lowest in the PROG group (12%). For all the prophylactic effects, PROG and CQ+PROG did not differ significantly. Thence, the deployment of CQ+PROG for prophylaxis would be unnecessary. Proguanil is a suitable alternative to chloroquine prophylaxis. Due to possible emergence of proguanil resistance, deployment of this drug should incorporate constant monitoring for resistance and the eventual prophylaxis efficacy. The search for other effective malaria control measures should continue. PMID- 8511809 TI - Factors that determine prevalence of use of contraceptive methods for men. AB - Globally, men have not shared equally with women the responsibility for fertility regulation. While family planning efforts have been directed almost exclusively toward women, the lack of male involvement may also reflect the limited options available to men. Current methods for men are either coitus-dependent, such as the condom or withdrawal, or permanent, such as vasectomy. The 20-year history of social science research on male contraceptive methods is examined here in terms of the human and method factors related to the acceptability of hypothetical methods and the prevalence of use of existing methods. New male methods, particularly if reversible, may alter men's willingness to accept or share responsibility for the control of fertility. Research opportunities in the areas of gender, decision-making, communication, health education, and service delivery will be enhanced when methods for women and men are comparable. PMID- 8511811 TI - Sensitivity of Plasmodium falciparum to chloroquine in pregnant women in Zaria, northern Nigeria. AB - Thirty-five pregnant women with Plasmodium falciparum parasitaemia were treated with chloroquine 25 mg/kg body weight over 3 days. They were followed up in vivo by use of a modified 14-day WHO extended field test. In vitro sensitivity of the parasite isolates to chloroquine was assessed by using the WHO microtest method. All pregnant women were aparasitaemic by day 7 and there was no parasite reappearance throughout the 14-day observation period. The mean parasite clearance time (MPCT) was 3.2 +/- 1.4 days. Eleven parasite isolates obtained from the women were highly susceptible to chloroquine in vitro. The effective drug concentration that gave 99% parasite growth inhibition (EC 99) was 0.36 mumol/l. PMID- 8511812 TI - Detection of IgM antibodies directed against the gut-associated circulating cathodic antigen in sera from Schistosoma mansoni infected patients. Development and comparison of three enzyme-linked immunoassays. AB - The majority of the human IgM antibodies detected with an immunofluorescence assay (IFA) on adult worms are directed against the gut-associated circulating cathodic antigen (CCA). In order to study this phenomenon further we developed and evaluated three related ELISA methods to specifically detect IgM antibodies against purified CCA. The assays employed: 1) direct coating of CCA, 2) indirect coating of CCA via a monoclonal antibody, and 3) IgM antibody-capture by rabbit anti-mu chain antibodies. Using a group of 46 positive sera, it was found that the three ELISA's and the IFA were significantly correlated. To discriminate between positive and negative sera we used a cut-off level of average reactivity + 3 standard deviations of 50 negative sera. False negative reactions were not found in any of the ELISA's, while both in the direct and indirect ELISA one false positive reaction occurred. For further studies or diagnostic use the antibody-capture ELISA is recommended. PMID- 8511813 TI - Louse-borne relapsing fever. A clinical and an epidemiological study of 389 patients in Asella Hospital, Ethiopia. AB - An outbreak of louse-borne relapsing fever, due to the return of soldiers to their original recruitment areas, after the end of thirty years of fighting in northern Ethiopia, was reported in Arsi region, southern Ethiopia. The epidemic spread to different members of the community and eventually the schools. We studied 389 patients affected by the epidemic and who were admitted to Asella Hospital between June 1991 and May 1992. Twenty-seven per cent of the patients were ex-soldiers; 28% were students, who were admitted to the hospital since the schools were opened after the summer vacations. The common clinical features of the disease were fever (99%), headache (92%), hepatosplenomegaly (66%), myalgia (55%), arthralgia (51%), petechial rash (43%), epistaxis (24%) and jaundice (23%). Observed complications were pneumonia (10%), pulmonary edema (6%), myocarditis (3%) and 6 abortions in 15 pregnancies. Patients were treated with low dose penicillin and i.v. fluids. The in-hospital case fatality rate was 3.6%. Jarisch-Herxheimer reaction occurred in 43% of the patients. 1.8% of the patients had relapses after treatment. PMID- 8511814 TI - Endocarditis in Ethiopia. Analysis of 51 cases from Addis Ababa. AB - Fifty-one cases of infective endocarditis in 47 Ethiopians over several years are analyzed. There were 32 males and 19 females, average age was 20.5, with 34 < or = 20. Only 2 patients had a known source of infection. Forty-four cases had underlying rheumatic heart disease, 7 had congenital heart disease of which 5 had patent ductus arteriosus. Staphylococcus aureus and S. epidermidis were the most commonly cultured organisms (10 each), only 1 streptococcus was isolated; 28/47 cultured cases had negative cultures. Eight patients (16%) died. In comparison with western studies, this group was much younger and had a higher prevalence of rheumatic heart disease. Mitral valve prolapse and degenerative valvular disease common in the West were not seen in this population. The rate of negative cultures was much higher than the 5-10% reported in the west, most likely due to previous use of antibiotics and problems with culture techniques. PMID- 8511815 TI - Psychiatric illness in first degree relatives of Nigerian schizophrenic and surgical control patients. AB - Psychiatric morbidity risk was assessed in 293 first degree relatives of patients with schizophrenia and 277 first degree relatives of surgical control patients using the family history method (FH-RDC). The morbidity risk for schizophrenia, alcoholism and schizoid personality disorder was significantly greater in relatives of schizophrenic patients. Affective disorder was difficult to diagnose using the family history method. Of the relatives of the schizophrenic probands who had psychotic illness 73.3% received treatment from traditional healers. The problem of social stigmatization of psychiatric illness was a deterrent to obtaining adequate family history, invariably the most reliable informant was the index proband. The problem was compounded by the paucity of and inaccessibility to treatment records from the traditional healers. PMID- 8511816 TI - Systemic allergic reaction and diarrhoea after pineapple ingestion. AB - Some foods may initiate allergic reactions. Anaphylaxis due to mangoes, oranges, nuts and other foods has been reported earlier. We report the clinical and laboratory features of 32 patients who became symptomatic shortly after they had eaten pineapples. Seventeen patients were males and 15 females with ages ranging from 5 to 70 years. Most of the patients complained of intense itching and urticarial rashes, followed by abdominal pain, vomiting and diarrhoea. Sixty eight percent of the patients became symptomatic within half an hour of eating the pineapple. On examination 18 patients had an urticarial rash and a flushed face. Although none of the patients were severely dehydrated, 20 patients presented with shock. Their peripheral pulse and blood pressure were low or absent suggesting an anaphylactoid reaction. The median total eosinophil count was 1850 (250-6375/mm3). The serum IgE level measured in 4 patients was raised. The patients were treated with intravenous fluids and antihistamine. Some patients also received steroid and adrenaline. All patients recovered uneventfully. Our findings suggest that ingestion of pineapple may occasionally cause an anaphylactoid reaction. PMID- 8511817 TI - Anaemia and wound healing. A clinical observation in 38 patients. AB - In a six year period, 38 patients who had an average packed cell volume of 17.9% (range 14-25%) were treated surgically and their anaemia was corrected with oral haematinics post-operatively. Twenty one of the patients had emergency while 17 had elective surgical procedures under spinal (N = 30), ketamine hydrochloride (N = 6) and local infiltrating (N = 2) anaesthesia. All the wounds healed by primary intention and no wound complication was observed after a mean follow-up period of three years. Headache following spinal anaesthesia occurred in 6 patients and was the only significant post-operative complication detected. We conclude that severe anaemia alone does not retard wound healing in man. PMID- 8511818 TI - Rhabdomyolysis associated with malaria tertiana in a patient with myoadenylate deaminase deficiency. AB - A male patient presented with malaria tertiana due to Plasmodium vivax. He developed a severe attack of rhabdomyolysis with acute renal failure. The patient was treated successfully with chloroquine medication. After complete recovery further muscle study revealed a deficiency of myoadenyl deaminase (MAD). The infection with P. vivax probably has been the triggering factor in the process of muscle necrosis, because the patient also had MAD deficiency. PMID- 8511819 TI - Ascarid granuloma presenting as pseudotumour. AB - Three patients with histologically confirmed ascarid granuloma who presented clinically with abdominal masses simulating abdominal tuberculosis or lymphoma are described. The clinical course of one patient was complicated by the formation of a spontaneous faecal fistula and perforation of the terminal ileum. In two cases there was rupture of the inflammatory pseudotumour through the anterior abdominal wall. PMID- 8511820 TI - Shigella osteomyelitis in a fit young man. AB - A case of shigella osteomyelitis in an apparently healthy young man is presented. Pre-operative and intra-operative swabs taken from the septic focus grew Shigella flexneri. Patient was successfully treated with surgery and a course of Ampicillin. PMID- 8511821 TI - Thalamic pain syndrome of Dejerine-Roussy. AB - For the general practitioner it is extremely difficult to make the diagnosis of the thalamic pain syndrome of Dejerine-Roussy which may develop in patients who have suffered a cerebrovascular accident. Because of this inability, the syndrome is considered rare in Africa. At the Teaching Hospital of the University of Calabar, Calabar, Nigeria two cases were seen recently however. We hereby present those two cases and discuss the aetiology, clinical presentation, diagnosis and treatment. This is intended to help the general practitioner to overcome the difficulties usually experienced in diagnosis and treatment of such cases. PMID- 8511822 TI - A comparison of nutritional status of pre-school children of cooperative and individual farmers in rural Ethiopia. AB - A cross-sectional study of nutritional status was carried out in Gondar region, Northwest Ethiopia in 1988. The objectives of the study were to compare the nutritional status of pre-school children of cooperative (Coops) and individual (Non-Coops) farmers and to determine factors accountable for the differences in the two groups of children, such as land size and income. A total of 376 children were studied. Although the overall malnutrition rate was found to be very high, the nutritional status of the pre-school children of the Coops was significantly better than that of the Non-Coops. The mean land size of the Coops and Non-Coops was 3.63 and 1.44 ha. and the mean annual income was 1,017 and 329 Ethiopian birr, respectively. PMID- 8511823 TI - Leprosy in students in Nigeria. PMID- 8511824 TI - A feasibility study on quantitating myocardial perfusion with Albunex, an ultrasonic contrast agent. AB - Quantitating regional myocardial perfusion has been the much sought-after but still elusive goal of many intensive investigations over the years. Videodensitometry of the variation of myocardial echogenicity in two-dimensional (2-D) echocardiograms as a function of time in conjunction with the injection of a bolus of an ultrasound contrast agent has been used clinically as a tool for a direct assessment of regional myocardial perfusion, despite that the precise relationship between tissue echogenicity observed on an image and the echoes detected by the ultrasonic probe is unknown. A study was undertaken to determine whether ultrasonic backscatter calculated from unprocessed radio frequency (RF) echoes returned from myocardium could be used to quantitate regional myocardium perfusion. A real-time ultrasonic scanner has been modified and interfaced to a microcomputer to acquire RF data at a rate up to 10 frames per second. Preliminary experimental data were obtained from four open-chest dogs following intracoronary injection of a bolus of Albunex and two dogs following intravenous injection with this modified scanner. On one hand, these results indicate that the integrated backscatter measured from the region of myocardium perfused by the coronary artery where Albunex is injected and selected for monitoring initially increases, reaches a peak, and then decreases as the contrast agent is washed out and that the magnitude of the peak is approximately linearly proportional to the volume concentration of Albunex microspheres injected, clearly demonstrating the feasibility of this approach for quantitating region myocardial perfusion. On the other hand, intravenous injections did not result in any appreciable change in myocardial backscatter in the left ventricle although a response could be observed in the left ventricular blood pool. PMID- 8511825 TI - Morphometry of intraluminal side-to-side differences in human basal cerebral arteries. AB - Intraindividual variability of Doppler frequencies in the basal cerebral arteries is higher than the variability in perfusion measurements. Since Doppler frequency is dependent on vessel diameter, we measured intraluminal vessel diameters post mortem. In 73 human cadavers, we measured fresh pairs of rings of the terminal internal carotid artery, the anterior and the middle cerebral artery. Mean intraluminal diameters (+/- standard deviation) for the respective vessel segments were 2.8 +/- 0.49 mm (2.72 +/- 0.49 mm), 1.61 +/- 0.37 mm (1.63 +/- 0.39 mm) and 2.10 +/- 0.38 mm (2.10 +/- 0.41 mm). The left/right ratio was 1.04 +/- 0.13, 1.05 +/- 0.35 and 1.02 +/- 0.17. Intraindividual asymmetries in intraluminal vessel diameters might be an additional factor in the interpretation of intracranial Doppler frequency measurements. PMID- 8511826 TI - On the Doppler signal from a steady flow asymmetrical stenosis model: effects of turbulence. AB - A steady flow model with a 70% (by area) asymmetrical stenosis was used to examine how changing flow regimes (laminar to turbulent) affect the Doppler signal. Human red blood cells (RBCs) (Hct = 42%) in saline were employed at a flow rate corresponding to a Reynold's number of approximately 545. A dilute suspension of 4% fixed RBCs was also used for the purpose of backscattered power comparison. Measurements of the Doppler signal enabled the backscattered power, time domain statistics, frequency spectra, frequency domain statistics, various spectral indices, autocorrelation function and decorrelation time to be calculated as a function of distance from the stenosis. It is shown that the characteristics of the Doppler signal measured at each site provide information on the nature of the insonated flow field and these correlate well with those expected. The results demonstrate that the onset of turbulence not only affects the Doppler spectrum but also has a profound effect on the signal power, the decorrelation time and the signal statistics. PMID- 8511827 TI - Ultrasound myocardial integrated backscatter signal processing: frequency domain versus time domain. AB - In the literature, different forms of measuring the ultrasound power returned by myocardial tissue are reported. Frequency domain methods will give the maximum frequency information, whereas time domain methods are limited in bandwidth, but more practical to realize. It was the purpose of this study to compare the various methods of signal processing. High frequency ultrasound signals from a pig's myocardium, digitally recorded during normal contractile performance, were analyzed by six different methods of signal processing to obtain estimates of backscatter power. The myocardial tissue characterization parameters studied were the integrated power as well as its cyclic variation during the cardiac cycle. A total number of 8109 ultrasound traces obtained in 16 pigs were processed. The study included three signal processing methods in the frequency domain: frequency compensated integrated backscatter calculated over both a large (4 MHz, method 1) as well as a small frequency bandwidth (2 MHz, method 2) and uncompensated integrated backscatter (method 3), and three methods in the time domain: high frequency signal squared and integrated (method 4), mean rectified signal level (method 5) and mean signal level after logarithmic compression and envelope detection (method 6). The random measurement variation (including beat-to-beat variation) was analyzed as well as the paired differences of the backscatter parameters obtained by the respective methods as compared with the only theoretically correct method in the time domain (method 4). The magnitudes of the random measurement variation expressed as a standard deviation (SD) were comparable (range 0.93-1.2 dB) except for method 6 (0.61 dB), where the measurement variation is decreased by the logarithmic compression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511828 TI - Temperature-dependent ultrasound color flow Doppler imaging in the study of a VX2 tumor in rabbits: preliminary findings. AB - Neovascularity in a VX2 carcinoma in rabbit liver was detectable, using an ultrasonic color Doppler flow imager. Intraportal infusion of heated saline increased the fractional area of color flow Doppler signals by at least 5% and as much as 30%, within and surrounding the tumors of all six rabbits studied. The effect of the fluid load was an increase in fractional area of color flow Doppler signals by 5 to 20% and was determined by the measurements following infusion and return to baseline temperature. The largest increment in color Doppler signal was observed in peritumoral vessels (10-40%). In contrast, the fractional area of color-coded pixels within the tumor was only slightly higher or lower (5-10%) at the peak temperature than at the baseline measurements. The temperature within the tumors was as much as 1 degree lower than parenchymal tissue in all animals measured. This was presumably due to the portal vein blood supply to normal tissue and predominantly hepatic artery supply to the pathological tissue. High velocities and persistent bidirectional flow were observed within the tumors only at the peak temperatures (> 43.5 degrees C). This experiment suggests that thermal stress may enhance tumor detectability by color Doppler imaging. Further development of a quantitative analysis method for color Doppler studies is needed. PMID- 8511829 TI - The effect of gas bubbles on the production of ultrasound hyperthermia at 0.75 MHz: a phantom study. AB - Transparent phantoms, made of bovine hide gelatine, have been constructed in order to study the consequences of the occurrence of cavitation in tissues. Gas pockets of about resonant size, physically introduced into the gel, lead to a mean temperature rise of 41 +/- 15 degrees C in 1 min, when the gel of concentration 11.4% (w/v) is sonicated in the continuous-wave (cw) mode at 1 W cm 2 (spatial average) and 0.75 MHz. Nyborg (1965) has shown that gas bubbles in a sound field can act as acoustic amplifiers and the observations reported here may be connected with this feature. A layer of gelatine foam was also used to introduce gas into the gel and in this case the temperature rise was about 12 +/- 5 degrees C under similar conditions. Without gaseous inclusions, the mean temperature rise in gel in 1 min was 2.3 +/- 0.2 degree C. At a gel/air interface, the rise per unit intensity per minute was 4.4 degrees C. It is concluded that in clinical situations, cavitation (or degassing due to supersaturation), when it does occur, is likely to be an undesirable consequence of ultrasound treatment. This finding, of large temperature rises in proximity to gas bubbles, is in broad agreement with the report by Hynynen (1991) of an excess temperature elevation of 60 degrees C in dogs' muscle in vivo during a 1 s pulse at 250 W cm-2 and 0.56 MHz. Other studies, by ter Haar and Daniels (1981) and Daniels and ter Haar (1986), of sonicated animal tissues in vivo, have found thresholds for bubble inception but no consequent temperature rise greater than 0.3 degrees C was observed. PMID- 8511830 TI - Cell density dependence of the ultrasonic degassing of fixed erythrocyte suspensions. AB - Ultrasonic cell lysis in vitro shows a strong dependence on the cell density of the suspensions. The major determinant in this phenomenon appears to be the suspended particle density per se. Reported are the results of experiments designed to test the hypothesis that the majority of the cell density effect arises as a consequence of the cell density-dependent formation of cellular aggregates around oscillating bubbles in an ultrasound field (Nyborg and Miller 1982), which in turn diminishes the potential for the occurrence and sustenance of destructive cavitational events in the bulk suspension fluid. The hypothesis was tested indirectly using manometric methods to measure ultrasound-induced release of dissolved gas from saline solutions and fixed erythrocyte suspensions. Ultrasonic degassing of the fluids in excess of that attributable to thermal effects was observed, and was suppressed by the presence of fixed erythrocytes when the cell density was greater than 5 x 10(6) cells/mL. At higher cell densities, the inhibition of ultrasonic degassing by fixed cells increased monotonically with increasing cell density, attaining complete suppression at a cell density of 5 x 10(8) cells/mL. The data thus support the hypothesis. PMID- 8511831 TI - [The "false positive" tumor marker in malignant testicular tumor]. AB - In addition to the histological diagnosis, alpha fetoprotein (AFP) and chorion gonadotropin (HCG) are used in clinical staging, therapy monitoring, and follow up. Elevated markers without localization of metastases by imaging procedures are generally classified as progressive disease. However, other causes may be responsible for the elevated tumor markers: other malignant or benign diseases such as hepatocellular carcinomas, gastrointestinal tumors, bronchial carcinomas and benign diseases of the liver for AFP, and vesicular mole, hepatocellular, stomach, pancreatic and urothelial carcinomas for HCG. Moreover, technical disturbances in the modern sandwich assays with monoclonal antibodies are possible by heterophilic antibodies. These human anti-animal antibodies are built after immunoscintigraphy, immunostimulation and oral immunization by macromolecules. As a result, if progressive disease of a malignant germ cell tumor is unlikely, several steps have to be taken to determine the true causes for the elevated tumor markers before chemotherapy can be applied. PMID- 8511832 TI - [Modified retroperitoneal lymph node excision in testicular tumors. Anatomy, surgical technique and results]. AB - Between January 1988 and June 1992, 56 patients suffering from malignant testicular tumors underwent nerve-preserving retroperitoneal lymphadenectomy at the University Hospital in Innsbruck. The tumors were staged according to the nomenclature recommended by the Workshop for Staging and Treatment of Testicular Cancer (Lugano 1979). According to this nomenclature 23 patients had stage I and 33 patients stage II. Thirty-nine patients presented with malignant teratoma, 3 with seminoma and 14 with teratoma and seminoma. The patients with stage I tumors were treated after orchiectomy with nerve-preserving retroperitoneal lymphadenectomy according to the dissection fields of Weissbach et al. In cases of nodal involvement in the retroperitoneum (stage IIa and IIb) a retroperitoneal modified lymphadenectomy according to the margins of Colleselli et al was performed. Patients with stage IIc tumors were treated with three cycles of polychemotherapy. Subsequently, the residual tumor was removed and, if possible, a nerve-sparing lymphadenectomy was performed. Since the nerve-preserving technique was modified in accordance with the tumor stage, antegrade ejaculation could be preserved in 47 of the 56 patients. In 22 patients exocrine testicular function was assessed by sperm analysis. The findings for the patients with stage I and IIa were considerable. The patients who had undergone induction chemotherapy for stage IIb and IIc had poor exocrine testicular function. The follow-up time was 29 months. At follow-up none of the patients presented with recurrent retroperitoneal tumor. Only one patient was found to have tumor progression (solitary pulmonary metastasis 1.7%). These results show that nerve preserving retroperitoneal lymphadenectomy is the treatment of choice in stage I non-seminomatous testicular tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511833 TI - [Malignant testicular tumors: cytogenetic and molecular biology principles]. AB - The common cytogenetic finding characteristic of human malignant testicular germ cell tumors is the presence of an isochromosome of the short arm of chromosome 12, i(12p), suggesting alterations in the proto-oncogenes (e.g., c-Ki-ras2) or putative tumor suppressor genes (TSG) that are localized here. However, to date there is no proof for such alterations. Conversely, alterations in expression of the retinoblastoma gene, a classical TSG, have been reported for the majority of testicular tumors. Other molecular genetic alterations have been described, affecting genes that are involved in the normal regulation of spermiogenesis, such as the c-kit gene product and its ligand SCF, as well as hst1, which is normally expressed in embryonal tissues only. The well-documented sensitivity of testicular tumors to chemotherapeutic agents may be caused by decreased activity of the glutathione S-transferase detoxification enzymes, as well as alterations of the expression of this gene family. PMID- 8511834 TI - [Current developments in chemotherapy of advanced testicular tumors]. AB - The chemotherapy of disseminated testicular cancer is subject to continuous change and further improvement. Because of the high efficacy, with a curability over 90% for patients with good prognostic criteria, ongoing trials investigate how far the toxicity can be reduced without a negative impact on the cure rate. Besides the standard protocols for good risk (PEB x 3; PE x 4) the substitution of cisplatinum by carboplatinum (CEB) or bleomycin by vinblastine (VPV;CEV) is currently being tested in prospective randomized trials. In patients with poor prognostic criteria, e.g. advanced disease according to the Indiana classification, the cure rate is only 50-60% with standard PEB x 4. The substitution of bleomycin by ifosfamide (PEI) seems to improve this result significantly, whereas dose escalation of platinum to double dose alone is not effective. A major advance can be expected from the early introduction of very high dose chemotherapy, within the first weeks of induction chemotherapy either by administration of megadose chemotherapy as a single cycle or by administration of sequential intermediate-dose cycles, using haematopoietic growth factors and peripheral blood progenitor cells. These types of dose-intensive regimens will be compared with standard PEB or PEI in prospective randomized trials in poor risk nonseminomatous germ cell tumours in first-line treatment as well as for salvage chemotherapy. For seminoma, however, due to the high platinum sensitivity the possibility of a carboplatinum single-agent chemotherapy for good risk seminoma patients is currently being investigated in prospective trials. The development of these new treatment strategies needs even more intense cooperation and joint effort from specialists in urology, surgery, radiotherapy, haematology, and medical oncology. PMID- 8511835 TI - [Methodologic comparison of the analysis of urinary calculi. Roentgen diffractometry, polarization microscopy and microscopic-microchemical component analysis]. AB - Not only instrumental, apparative or operative stone extraction is necessary for patients with urolithiasis (particularly those with recurrent urolithiasis); preventive treatment is also called for, and for this exact analysis of the composition of the stones is essential. The procedures currently accepted as standard for stone analysis are: X-ray diffraction, infrared spectroscopy, polarisation microscopy and the complicated chemico-quantitative analyses performed in some institutes. Recently a new, so-called microscopic microchemical, analysis of stone components has been presented (the Harzalith). To test the value of this procedure as compared to e.g. X-ray diffraction or polarization microscopy, a comparative study was carried out in our department. Thirty different urolith compositions (calculi with one and with more components) were analysed qualitatively and quantitatively by three methods. No qualitative difference was found between X-ray diffraction and polarization microscopy; however, there was a difference from the Harzalith method, and with increasing number of components there was hardly any correspondence with the other methods. Only 10% of the calculi with three or four components could be analysed correctly. Often, too many components were determined by the new method. The test material was analysed by three laboratory assistants working independently of each other. PMID- 8511836 TI - [Duplex ultrasound of the penis. Value of a new diagnostic procedure based on over 1,000 patients]. AB - In the period between December 1989 and December 1991, penile duplex sonography was performed, mostly after intracavernous injection of prostaglandin E1 in more than 1000 patients with erectile dysfunction or other penile disorders (Peyronie's disease, penile deviations, priapism). The most reliable evaluation criterion was the assessment of the peak flow velocity. Values of more than 25-30 cm/s with reference to the deep penile artery and more than 35-40 cm/s with reference to the dorsal artery indicated the integrity of the penile arteries. The assessment of the resistancy index has not proved to be a useful criterion because of its dependence on diastolic blood flow and therefore on the erection state, especially in cases of so-called cavernous insufficiency. Similar observations were made concerning the assessment of the increase in diameter of the deep penile arteries after intracavernous application of vasoactive drugs. Based on the fact that the increase in diameter is more dependent on the relaxation capacity of the cavernous smooth musculature and not on the actual blood flow, the measured values may be equal both in normal and in clearly disturbed blood circulation. In conclusion, duplex sonography is at present, together with color Doppler imaging, the most reliable vascular diagnostic tool and has clearly proved its superiority both to conventional penile Doppler imaging and penile angiography. PMID- 8511837 TI - [Tableau de l'operation de la taille by Marin Marais (1725)--a bladder calculus operation represented in music]. AB - The piece "Tableau de l'operation de la taille", written for viola by the French composer Marin Marais in 1725, presents an operation for removal of a stone in the bladder in musical form. Musicological analysis shows that in the early 18th century the lateral perineal approach was normally used for such operations in France. Medico-historical annotations complement the musicological analysis. PMID- 8511838 TI - [Effectiveness of the BR-Test and the Intest in the determination of chemotherapeutic residues in raw and preserved milk]. AB - Negative detection of residues of inhibitory substances has become one of the standard quality traits of raw milk also in the Czech Republic. Hence a requirement appeared in 1991 to evaluate the usability of two commercially produced microtitration tests for this purpose. The tests of BR-TEST (Enterotox) and INTEST (Mlekarensky prumysl) were performed in weekly intervals for the time longer by a week than is the declared expiration, that means seven replications in BR-TEST and five replications in INTEST. Compact and stripped microplates (STRIPS) designated BR-TEST "AS", BR-TEST 12x8 "AS" and INTEST C-96 type and INTEST 0-96/6x16 were used for the tests. The principle of inhibition demonstration in the concentration series of selected drugs was applied. The drugs were chosen with respect to the frequency of their use for clinical treatments in the CR. Tab. II shows the used drugs and concentration series. The following parameters were tested: detection limits, reproducibility, effect of milk preservation, and the declared expiration. Tab. III shows detection limits. It is apparent the BR-TEST detection responses to streptomycin and chloramphenicol were lower in BR-TEST than in INTEST in our experiments. The responses to penicillin, oxacillin and oxytetracycline were lower in some cases, and equal in other ones. On the other hand, the INTEST detection response to sulfadimidin was markedly lower in comparison with BR-TEST. Tab. IV summarizes the range of detection limits in milk with Heeschen's reagent. In our experiments the detection response of BR-TEST to the tested chemotherapeutics was lower in some cases, in other cases it was the same as in INTEST.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511839 TI - [DNA fingerprinting in horses]. AB - Using a multilocus DNA probe, individual - specific hybridization patterns, the so-called DNA fingerprints (TAB) were determined in six horse families by the DNA fingerprinting method. The probe with evolutionally preserved nucleotide sequence from bacteriophage M13 determines hypervariable regions placed in genomic minisatellite DNA. The use of this probe permits an identification of an individual and execution of paternity relationships with a probability over 99.99 per cent. PMID- 8511840 TI - [The effect of cadmium on indicators of rumen fermentation and their levels in biological material in sheep]. AB - The experiment was carried out with three groups, each consisting of six adult sheep of the Merino breed weighing 40-45 kg, fed with the diet composed of 1 kg of meadow hay and an addition of 0.2 kg of barley meal for 3 weeks before the experiment. The first group - the control - was provided the natural supply 0.09 mg Cd/kg DM of the diet, the supply of Ist experimental group was increased by 5 mg Cd/kg DM and of the IInd experimental group by 10 mg Cd/kg of diet DM in the form of sulphate. The influence of mentioned cadmium doses on levels of volatile fatty acids, their energetic yield and proportion of their energy and energy of methane and bacterial mass from the energy of fermented feed hexose, as well as the total number of infusoria and number of infusoria of Entodinium sp. in the ruminal fluid of sheep with an increased supply of cadmium were examined during seven weeks. In addition to that cadmium contents in the liver, kidneys, muscles, excrements and ruminal fluid was investigated. Obtained results indicate that yet a lower supply of cadmium amounting to 5 mg and 10 mg/kg DM of the sheep diet, had significant negative influence (Tab. I) on the production of isobutiric acid in rumen fluids and decreased significantly (Tab. III) the total counts of infusoria and number of Entodinium sp. infusoria in the rumen fluids of sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511841 TI - Demonstration of parvovirus in diarrhoeic African cheetahs (Acinonyx jubatus jubatus Schreber, 1775). AB - Parvovirus was demonstrated in the intestinal content of diarrhoeic African cheetahs by electron microscopy. The virus was isolated in a feline kidney cell line inoculated with a filtrate of the intestinal content. Its growth characteristics, cytopathic effect, agglutination of porcine erythrocytes, structure, and results of immunoelectron microscopic examination were indistinguishable from those of feline panleukopenia virus. PMID- 8511843 TI - A comparison of acute pull-out strength between two-way and one-way transfixation pin insertion for external skeletal fixation in canine bone. AB - This study tested the hypothesis that two-way insertion of an external skeletal fixator transfixation pin would weaken the pin-bone interface. Smooth and partially threaded (end) transfixation pins were placed in tibiae of 32 cadavers by slow speed drilling or hand placement through a predrilled pilot hole. In one bone of each tibial pair, pins were inserted 2 cm beyond the distal cortex and retracted to a predetermined position (two-way). In the contralateral limb, the pins were inserted in one forward motion to the predetermined position (one-way). The peak force (Newtons) required to extract the pins (pull-out strength) axially at a rate of 1 mm/sec was determined by using a universal testing machine. A significant (p < .05) decrease in pull-out strength was found in pins placed by two-way insertion (674 +/- 410) as opposed to one-way insertion (766 +/- 432). The results of this in vitro study suggest that one-way insertion should be used clinically to decrease weakening of the pin-bone interface and prevent possible failure of external fixators. A significantly greater pull-out strength was found for threaded pins placed in the proximal diaphysis (1459 +/- 330 Newtons) compared to the distal metaphysis (873 +/- 297 Newtons). PMID- 8511842 TI - Resection of pulmonary metastases in canine osteosarcoma: 36 cases (1983-1992). AB - Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both. Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma. PMID- 8511844 TI - Arthroscopy of the coxofemoral joint of foals. AB - An arthroscopic procedure for examination of the coxofemoral joint was developed in nine foals (four cadavers, five anesthetized) to determine if access was sufficient for evaluation and surgical treatment of intra-articular lesions. The joint was distended and the arthroscope inserted through the notch (incisura trochanterica) between the cranial and caudal parts of the greater trochanter. This portal allowed examination of the cranial, lateral, and caudal aspects of the joint. Mechanical distraction of the joint through an instrument portal located 2 to 4 cm cranial and 1 to 2 cm ventral to the arthroscope portal allowed examination of the ligament of the head of the femur, the femoral head, and articular and nonarticular surfaces of the acetabulum. Adduction and rotation of the limb improved visualization of the craniomedial and caudomedial portions of the femoral head. Traction applied to the distal limb allowed visualization of the same structures that were observed when mechanical distraction was used. Traction also created space for placement of surgical instruments into the joint through the instrument portal. Access to most regions of the joint was adequate, but access to the caudal and medial aspects of the joint was limited. Three foals were killed while they were anesthetized, and their coxofemoral joints were dissected. Two foals were allowed to recover from anesthesia and were observed for 30 days after surgery. One foal was mildly lame for 2 days after surgery. The other foal was not lame after surgery. The incisions healed, and the coxofemoral joints were radiographically normal by postoperative day 30. PMID- 8511845 TI - Arthrodesis of the distal interphalangeal joint in two horses using three parallel 5.5-mm cortical screws. AB - The distal interphalangeal joint was successfully arthrodesed in two horses using three parallel 5.5-mm cortical screws and an autogenous cancellous bone graft. The screws were directed from the palmar proximal border of the second phalanx dorso-distally across the joint space and into the third phalanx. The technique was first developed on a normal horse. The second horse, a clinical case, ruptured its deep digital flexor tendon with complete luxation of the distal interphalangeal joint. Bony fusion of the distal interphalangeal joint occurred in both horses, but both also had residual lameness at a walk. Twenty-one months after the arthrodesis procedure, the clinical patient died from complications related to a subsolar abscess in the operated limb. PMID- 8511847 TI - Surgical treatment of intramural esophageal inclusion cysts in three horses. AB - Three horses were diagnosed as having esophageal inclusion cysts. Clinical signs included dysphagia, swelling of the cervical esophagus, and salivation. Surgical removal of the cyst was attempted in two horses. Both horses survived, but multiple complications occurred, including esophageal fistulation and neurovascular damage. Marsupialization of the cyst was performed in the third horse. The stoma closed 3 weeks after surgery without complications, and endoscopic examination revealed a grossly normal esophagus. Marsupialization may be preferable to surgical removal for treatment of selected esophageal inclusion cysts in horses. PMID- 8511846 TI - Excision of intralaryngeal granulation tissue in 25 horses using a neodymium:YAG laser (1986 to 1991). AB - Granulation tissue masses arising from the axial surface of the arytenoid cartilage in 25 horses were excised using a contact neodymium:yttrium aluminum garnet laser. A technique that eliminated the need for general anesthesia or laryngotomy was developed for transen-doscopic removal of the masses in standing horses. Nineteen racehorses made abnormal upper respiratory tract noises or their performance was decreased, whereas six horses not used for racing had a history of stertor (five horses) or epistaxis after nasogastric intubation (one horse). Thoroughbreds were significantly (p = .0126) overrepresented compared with the hospital population. The granulation tissue masses were successfully excised and the defect healed in all 25 horses, although a second excision of granulation tissue regrowth was necessary in four horses. In 21 horses, the underlying chondrosis did not progress appreciably. In four horses with preexisting moderate arytenoid cartilage thickening and concurrent laryngeal abnormalities, the surgery site healed but the underlying chondrosis progressed substantially. Twelve of 19 (63%) racehorses returned to race at least three times after the surgery. Of the 19 racehorses, five had only slight arytenoid cartilage involvement whereas 14 had moderate cartilage thickening or concurrent laryngeal pathology. All five horses with slight apparent arytenoid cartilage involvement and no concurrent laryngeal pathology returned to racing. Seven of the 14 horses (50%) with moderate underlying cartilage thickening or concurrent laryngeal pathology returned to racing. The six horses not used for racing returned to their previous activity without further respiratory problems. PMID- 8511848 TI - Analgesia after lateral thoracotomy in dogs. Epidural morphine vs. intercostal bupivacaine. AB - One of two analgesic treatments was randomly assigned to 40 dogs undergoing lateral thoracotomy. Group E (20 dogs) received an epidural injection of morphine (0.1 mg/kg) before surgery. Group I (20 dogs) received injections of bupivacaine around five intercostal nerves when the thorax was about to be closed. All dogs were given an opioid as part of their preoperative medication (meperidine or butorphanol), followed by thiopental for induction and halothane or methoxyflurane for maintenance of anesthesia. Scores were assigned for pre operative demeanor and response to restraint and injection. Alertness, undisturbed pain behavior, and response to palpation of the wound were assessed 3, 6, 12, and 24 hours after surgery. Dogs that appeared uncomfortable were given analgesics. Blood for evaluation of arterial blood gases was obtained at 3 and 6 hours after surgery. The person scoring the dogs was blinded to the treatment given. There were no statistically significant differences between the groups. Group E contained more "nervous" dogs (12 vs. 6) and more dogs in group E received postoperative analgesics (8 vs. 2). Both techniques appeared to provide adequate analgesia for most dogs. PMID- 8511849 TI - Comparison of cerebrospinal fluid pressure in propofol- and thiopental anesthetized eucapnic dogs. AB - Cerebrospinal fluid pressure (CSFp) was measured as part of the neurologic assessment of dogs with suspected intracranial disease. Because propofol has not been shown to cause an increase in intracranial pressure in humans, the authors examined its effect on (CSFp) in dogs to determine if it would be an appropriate substitute for thiopental as an anesthetic agent for the measurement of CSFp. The CSF pressure in eucapnic propofol-anesthetized dogs (105 +/- 5.6 mm H2O) was not significantly different (p < .05) from CSFp in eucapnic thiopental-anesthetized dogs (103.8 +/- 6.6 mm H2O). PMID- 8511850 TI - Effect of hypercapnia or xylazine on lateral ventricle and lumbosacral cerebrospinal fluid pressures in pentobarbital-anesthetized horses. AB - Facial artery pressure, central venous pressure, heart rate, and lateral ventricle cerebrospinal fluid (CSF) pressure (LV-CSFP) were measured in 10 pentobarbital-anesthetized horses at arterial partial pressure of carbon dioxide (PaCO2) values of 40, 60, and 80 mm Hg, produced by varying the inspired carbon dioxide concentration. Variables were recorded at 5-minute intervals for 15 minutes at each level of PaCO2. Arterial blood gas analysis was performed at the end of the 15-minute time period for each level of PaCO2. Lateral ventricle CSF pressure was significantly increased (p < .05) at a PaCO2 of 80 mm Hg. Cardiovascular variables were not significantly changed by changing PaCO2. The PaCO2 was returned to 40 mm Hg; 1.1 mg xylazine/kg body weight was injected intravenously in eight horses, and data were collected for 60 minutes. No significant changes were observed. No changes were observed in two control horses not receiving xylazine. Subsequently, placement of a lumbosacral subarachnoid catheter allowed simultaneous measurement of LV-CSFP and lumbosacral CSF pressure (LS-CSFP) at PaCO2 values of 40, 60, and 80 mm Hg. The Pearson Correlation Coefficient between LV-CSFP and LS-CSFP was 0.94 (p < .0001) It was concluded that changes in CSF pressure could be detected at the lateral ventricle and the lumbosacral space; increasing PaCO2 to 80 mm Hg resulted in significant increases in LV-CSFP; xylazine does not increase LV-CSFP in pentobarbital-anesthetized, normocapnic horses; and under the conditions of this experiment, LV-CSFP and LS CSFP were closely correlated. PMID- 8511851 TI - Cardiorespiratory effects of combined midazolam and butorphanol in isoflurane anesthetized cats. AB - The cardiorespiratory effects of midazolam (0.1 mg/kg) and butorphanol (0.4 mg/kg) were evaluated in seven cats. Cats were induced in a chamber, removed and intubated, and maintained with isoflurane in 100% oxygen. Cardiorespiratory data were recorded before and 3, 10, 20, 30, 40, 50, and 60 minutes after intravenous injection of midazolam-butorphanol. Heart rate, mean arterial pressure, and respiration rate were significantly (p < .05) decreased below baseline at various times throughout the study. Tidal volume and minute ventilation were unchanged. End-tidal carbon dioxide was significantly (p < .05) increased above baseline for 30 minutes. Midazolam-butorphanol administered intravenously induced significant alterations in several cardiorespiratory parameters in isoflurane-anesthetized cats. PMID- 8511852 TI - Hemodynamic effects of atropine and glycopyrrolate in isoflurane-xylazine anesthetized dogs. AB - Alterations in parasympathetic tone are partially responsible for xylazine's hemodynamic effects. The purpose of this study was to evaluate and compare the hemodynamic changes caused by the administration of intravenous (IV) atropine or glycopyrrolate after IV xylazine in isoflurane-anesthetized dogs. Six healthy beagles (8.2 to 10.7 kg) were used in two trials separated by 7 days. Anesthesia was induced and maintained with isoflurane in 100% oxygen with controlled ventilation. Once constant end-tidal isoflurane (1.8%) and arterial partial pressure of carbon dioxide (35 to 45 mm Hg) values were reached, baseline data were recorded and xylazine (0.5 mg/kg, i.v.) was given. In trial 1 atropine (0.1 mg/kg, i.v.) was given 5 minutes after xylazine, and in trial 2 glycopyrrolate (0.025, mg/kg, i.v.), was given 5 minutes after xylazine. Hemodynamic variables were recorded 3 minutes after xylazine and 3 minutes after anticholinergic administration. In trial 2, bilateral vagotomies were performed 10 minutes after glycopyrrolate, and hemodynamic variables were recorded 3 minutes later. Heart rate, cardiac index, and stroke index decreased; arterial pressure and systemic vascular resistance increased after xylazine. Heart rate, cardiac index, and rate pressure product increased after anticholinergic administration. Significant differences between atropine and glycopyrrolate were not observed in any of the hemodynamic parameters. Similarly, significant differences between glycopyrrolate and bilateral vagotomy were not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511853 TI - Abnormal hemostatic profiles and gastric necrosis in canine gastric dilatation volvulus. AB - Hemostatic profiles (prothrombin time, activated partial thromboplastin time, fibrinogen concentration, fibrin degradation product concentration, platelet count, and antithrombin III activity) were acquired prospectively in 20 dogs with a diagnosis of gastric dilatation-volvulus. Eighteen dogs had abnormal results of one or more hemostatic test, including eight dogs that had hemostatic profiles consistent with a diagnosis of disseminated intravascular coagulation. During surgery, or at necropsy, the dogs' stomachs were evaluated for gross abnormalities, and lesions were graded subjectively as mild, moderate, or severe. Eight dogs had mild gastric lesions, five had moderate lesions, and seven had severe changes indicating gastric necrosis. Seventy percent (7/10) of the dogs with two to six abnormal hemostatic test results had gastric necrosis, whereas none of the 10 dogs with no or one abnormality had gastric necrosis (p < .001). A multiple linear regression equation, based on fibrin degradation product concentration, activated partial thromboplastin time, and antithrombin III activity was derived to predict gastric necrosis. This equation correctly identified gastric necrosis with 86% sensitivity, 100% specificity, 100% positive predictive value, and 93% negative predictive value. PMID- 8511854 TI - Surgical management of congenital urethral sphincter mechanism incompetence in eight female cats and a bitch. AB - Congenital urethral sphincter mechanism incompetence is a cause of urinary incontinence in female dogs and cats. In some of these animals, urethra hypoplasia is the primary diagnosis, with the urethra being almost absent in some patients. Treatment of this problem can be difficult. This paper describes two techniques for the surgical treatment of eight cats and one dog with severe urethral hypoplasia. In five animals, partial excision of the bladder neck was performed to create a longer "urethra." In the other four, an attempt was made to conserve bladder volume while simultaneously creating a urethra with a bladder neck flap reconstruction technique. One cat was lost to follow-up, but the clinical signs resolved in three cats and the remaining animals improved. Two cats had recurring cystitis, possibly associated with bladder neck diverticula because of uterine horn remnants terminating abnormally in the bladder. The results in this limited series suggest that reconstructive surgery in cases of severe urethral hypoplasia improves continence control. PMID- 8511855 TI - [The differential use of impulse low-frequency currents (interference and sinusoidal modulated) in treating patients with chronic pancreatitis]. PMID- 8511856 TI - [The effect of different physical loads on the central and cerebral hemodynamics of patients with a history of stroke]. AB - Seventy-eight postapoplectic patients were examined in comparison with healthy subjects. During exercise tests (foot and hand bicycle ergometry, wrist ergometry) registration was performed of central and cerebral hemodynamics. Three types of hemodynamic responses to various exercise tolerance tests were recognized which should be taken into consideration when assigning kinesitherapy to postapoplectic patients. PMID- 8511857 TI - [The combined use of therapeutic physical factors in patients with spondylogenic circulatory encephalopathies]. AB - Troxevasin vacuum-phonophoresis and low-intensity laser irradiation on reflexogenic collar zones demonstrated statistically significant effectiveness. The treatment was used in 94 patients with spondylogenic discirculatory encephalopathy stage I-II. PMID- 8511858 TI - [Experience in using hyperthermia in combination with the radon pool in the combined treatment of patients with arteriosclerosis obliterans at the Belokurikha health resort]. AB - The patients with atherosclerosis obliterans of the peripheral arteries received sanatorium treatment at Belokurikha health resort. The treatment (thermoradonotherapy) involved hyperthermia in sauna combined with radon pool. The above combination turned out superior to conventional radonotherapy provided the procedures were well tolerated and no balneoreactions arose. PMID- 8511859 TI - [Decimeter-wave therapy in combination with dimexide and mud applications in the combined treatment of osteoarthrosis patients]. PMID- 8511860 TI - [The 70th anniversary of the journal Voprosy kurortologii, fizioterapii i lechebnoi fizicheskoi kul'tury]. PMID- 8511861 TI - [The dynamics of myocardial contractile capacity in patients with osteoarthrosis deformans using different combinations of health resort therapy]. AB - The character of changes in the parameters of the cardiac phase analysis (left ventricle) shows an evidence of a favourable effect of adequate mud-balneotherapy on the myocardial contractility in 91 patients suffering from osteoarthrosis deformans. But such a treatment effect on heart activity was less evident in cases when mud-balneotherapy with humisol was used. PMID- 8511862 TI - [The effect of cryo- and cryoelectrotherapy on neuromuscular function in coxarthrosis patients]. AB - Cryotherapy (CT) and cryoelectrotherapy (CET) in combination with therapeutic exercise were assessed for neuromuscular effects in patients with coxarthritis and necrosis of caput femoris. The above complex is found effective in reducing the rigidity of the muscles and joints, in attenuation of functional contractures. It increases muscle strength nearby the affected joints. The best results were achieved with CET. Single CT and CET procedures increase the amplitude of muscular bioelectrical activity at maximal muscular tension, the highest effect being observed at the sites of the direct exposure. Marked analgetic activity of the physical factors was confirmed by electroneuromyographic findings. PMID- 8511863 TI - [The correction of the manifestations of the pathological alterations to the hip joints after the reduction of congenital hip dislocation in children]. AB - The paper outlines mechanisms underlying the development and predetermining the forms of hip joint disorders consequent to setting of congenital hip dislocation, the results of a 3-8-year follow-up of relevant 75 cases in children. Individual treatment regimens combined appropriate exercise, biomechanical correction, physiotherapy, acupuncture, manual therapy. PMID- 8511864 TI - [The use of sinusoidal modulated currents with different sites of action for restoring the work capacity of highly qualified athletes]. PMID- 8511865 TI - [The microbiological aspects of assessing the quality of potable fresh and mineral waters]. PMID- 8511866 TI - [New methodological approaches to identifying waters of the naftusia type and the results of their use for evaluating the conditions for operating the Truskavets spring]. PMID- 8511867 TI - [The assessment of the efficacy of sulfate-sodium-calcium mineral water in the treatment of chronic gastritis with secretory insufficiency]. PMID- 8511868 TI - [The early rehabilitation of patients at the sanatorium-health resort treatment stage after a performed cholecystectomy]. PMID- 8511869 TI - [Physical loads and psychotherapy in the combined sanatorium treatment of children with the autonomic vascular dystonia syndrome]. PMID- 8511870 TI - [The morphological changes in the adrenal cortex under the action of the helium neon laser and obzidan]. PMID- 8511871 TI - [The rehabilitative treatment of patients following gastric resection at the hospital stage]. AB - To diminish the frequency of postoperative pulmonary complications following gastric resection and stay in hospital, a complex of preventive and therapeutic measures has been designed and tested in 165 patients. The complex involves early exercise, aerosol therapy, vibratory massage, heparin electrophoresis of the chest. Clinicophysiological data on respiratory function, pulmonary circulation, hemocoagulation support the effectiveness of the rehabilitation in patients after gastric resection. PMID- 8511872 TI - [The function of the hypophysis-gonadal system in lumbar osteochondrosis in men and its changes during acupuncture and electroacupuncture]. PMID- 8511873 TI - [The problem of optimizing sanatorium-health resort treatment]. PMID- 8511874 TI - [A pool for therapeutic swimming]. PMID- 8511875 TI - [A new method of massage for patients with chronic salpingo-oophoritis]. PMID- 8511876 TI - [Activity of 5'-nucleotidase from thymus and tumors upon administering bradykinin to tumor-bearing mice]. AB - Activity of 5'-nucleotidase was inhibited in thymus tissue of tumor-bearing mice; bradykinin (1 mg/kg body weight) increased the enzymatic activity 2.0-2.2-fold. Administration of bradykinin led to inhibition of allogenic Crocker's sarcoma growth and to stimulation of syngeneic mastocytoma P-815 growth, which was inoculated into noninbred and BALB/c mice, respectively. Hence, bradykinin activated 5'-nucleotidase in Crocker's sarcoma and did not affect the enzymatic activity in tumor P-815. This suggests that activity of 5'-nucleotidase is of importance in evaluation of the thymus tissue state as well as it demonstrates the tumoral tissue sensitivity to bradykinin. PMID- 8511877 TI - [Synthesis of cell membrane "signal" ATP in human erythrocyte membranes stimulated by insulin as criteria of the efficacy of therapeutic plasmapheresis]. AB - Insulin-stimulated synthesis of plasma membraneous "signal" ATP (psATP) from ADP and P(i) in oxidation coupled with that of NADH was detected in a preparation of plasma membranes from human erythrocytes; psATP was formed at concentrations of 10(-8)-10(-9) M. Effect of medicinal plasmapheresis on ability of erythrocyte membranes to produce psATP was studied. The rate of psATP biosynthesis was estimated in healthy volunteers and in patients with various diseases: nonspecific aortic arteritis, bronchial asthma, peritonitis, myasthenia before and after plasmapheresis. Distinct values of basal content of ATP (without insulin) and insulin-stimulated biosynthesis of ATP were detected in volunteers. Elevation of ATP biosynthesis, in response to insulin effect, was equal to 8.029 +/- 0.163 nmol/mg of membrane protein per min. Estimation of the psATP biosynthesis rate in patients with various pathological states enabled to detect markedly that psATP content tends to increase after plasmapheresis. Absolute values of psATP content were distinctly lower in these patients than those in healthy volunteers, while after plasmapheresis these parameters approached the normal level. Estimation of the insulin-stimulated synthesis of psATP may serve as a valid criterion of plasmapheresis efficiency. PMID- 8511878 TI - [The role of a cosubstrate in the kinetic mechanism of action of mollusk thiaminase I]. AB - Mechanisms of interaction between thiaminase I and cosubstrate were studied using thiazole-2-14C-thiamine and 14C-nicotinic acid. The dissociation constant of nicotinic acid in the presence of the enzyme was of an order of 1 x 10(-6) M. A mechanism of the prestationary phase of a thiaminase reaction at -10 degrees was studied. The low temperature step, which demonstrated specific characteristics, was involved in analytic estimation of total thiamine concentration in vitro. Native thiaminase I from the bivalve mollusca Anodonta cygnea proved to be a holoenzyme. PMID- 8511879 TI - [Biochemical aspects of the pathogenesis of generalized meningococcal infection]. PMID- 8511880 TI - [Lipid peroxidation processes and activity of brain succinate dehydrogenase in experimental craniocerebral trauma]. AB - A statistically significant decrease in the activity of succinate dehydrogenase (SDH) was found in the rabbit brain after craniocerebral injury. The decrease in the activity of brain SDH was not shown to result from "competitive inhibition" by malonate accumulated after activation of lipid peroxidation. The activity of brain SDH was normalized by directed modification of the function of the central nervous system via administration of phenamine (amphetamine) into the injured animals. PMID- 8511881 TI - [The effect of edematous factors on the blood protein system during development of cerebral edema and swelling]. AB - Initial abnormalities develop in nervous tissue during brain swelling and edema. Toxic and traumatic forms of brain swelling and edema were simulated in rats. The content of total protein as well as albumin and globulin fractions were estimated in blood serum. The alterations in the levels of serum protein fractions in brain swelling and edema were essential in the development of the impairment. PMID- 8511882 TI - [Brain monoamine oxidase in aging wild Norway rats, chosen for lack of aggressive behavior toward humans]. AB - Monoamine oxidase A and B (MAO A; MAO B) activity was studied in the brain stem and hemispheres of young (4 months) and old (7 months) wild Norway rats of S35 S36 bred for absence of aggressive reactions to men (tame), bred for pronounced aggressive reaction for the same number of generations (aggressive), and those not undergoing any breeding (wild). In young tame rats MAO B activity was lower than in wild ones of the same age. As the animals grew older, in 7 months, MAO B activity increased in the brain stem and hemispheres of all the rats, irrespectively of the type of behavior. Difference in MAO B activity found between tame and wild 4-month rats disappeared at the age of 7 months. MAO A activity did not change either with ageing or due to breeding for behavior. PMID- 8511883 TI - [Correction of lipoprotein lipid peroxidation in experimental atherosclerosis with polyunsaturated fatty acids combined with antioxidants]. AB - Atherosclerotic lesion of the aorta and lipid peroxidation (LPO) in blood and in lipoproteins produced in hepatocytes were studied in rabbits with experimental atherosclerosis maintained on a diet enriched in polyunsaturated fatty acids containing in corn oil (2 ml/kg daily during 30 days) and antioxidants alpha tocopherol and carnosine (2.5 mg/kg and 50 mg/kg, respectively, daily during 30 days). This diet exhibited a hypocholesterolemic effect accompanied by approximately a 10-fold decrease of the impaired aortic area, as well as lowered content of 2-thiobarbituric acid-positive LPO products occurring in blood and, especially, in apoB lipoproteins. The antioxidant-containing diet decreased distinctly the content of LPO products both in the liver tissue homogenate and lipoprotein fraction (d < 1.065 g/cm3) produced by hepatocytes during 30-min perfusion of liver tissue. The findings suggest that the diet enriched in polyunsaturated fatty acids and antioxidants contributed to a decrease of LPO products content in the blood serum and apoB lipoproteins as well as to the inhibition of lipoprotein oxidation during their synthesis in liver cells; the diet may be recommended for the prophylaxis and treatment of atherosclerosis. PMID- 8511884 TI - [Level of lipids and apolipoproteins in obesity]. AB - The level of lipids and apolipoproteins was studied in the serum of patients with various degrees of obesity without hormonal impairments in order to find interrelationship between obesity and atherosclerosis development. 14 men and 42 women aged 19-59 years were examined. Concentration of triglycerides and very low density lipoprotein (VLDL) cholesterol was distinctly higher in obese patients of both sexes than in normal weight persons. However, content of apo A-I and apo B was similar in blood of both obese and normal persons, while concentration of apo E was higher in obesity. In obesity, the ratio HDL cholesterol/A-I was decreased, thus indicating that the HDL3/HDL2 ratio was altered, showing a decreased content of the latter subfraction. The findings suggest that impairment in metabolism of mainly HDL and VLDL subfractions occurred in patients with obesity. These impairments were atherogenic and may be responsible for a high risk for atherosclerosis and heart ischemic disease in obese patients. PMID- 8511885 TI - [Activity of lysosomal enzymes in diabetes mellitus patients along with diffuse enlargement of the thyroid gland]. AB - Activity of lysosomal enzymes was studied in 68 patients with Types 1 and 2 diabetes mellitus concurrent with diffuse thyroid enlargement. A decrease in activities of beta-galactosidase and DNAase and activation of cathepsins were detected in the leukocytes fraction from patients with Types 1 or 2 diabetes mellitus, thus demonstrating that metabolic impairments occurred in diabetes mellitus. These patterns were improved after intensive insulin therapy. Hyperfunction of the thyroid gland in patients with moderate Type 1 diabetes mellitus normalizes the activity of lysosomal enzymes. PMID- 8511886 TI - [Study of gamma-aminobutyric acid (GABA) concentration in blood plasma of alcoholism patients]. AB - Concentration of gamma-aminobutyric acid (GABA) was estimated in the plasma of 104 patients with alcoholism during 2 month treatment course in addiction hospital and in 29 healthy volunteers. Highly distinct differences in content of GABA were detected in the plasma of the volunteers and patients with alcoholism, which remained within 60 days of alcohol withdrawal. PMID- 8511887 TI - [Possible ways of regulating detoxifying processes in the alcohol dehydrogenase reaction with pantothenic acid derivatives]. AB - Oxidation of derivatives and precursors of pantothenic acid was studied in alcohol dehydrogenase reactions. Despite the presence of free hydroxymethyl groups in a number of pantothenic acid derivatives only panthenol with Km = 8 x 10(-3) M was shown to serve as a substrate for alcohol dehydrogenase from horse liver tissue (EC 1.1.1.1) Pantethine, sodium phosphopantothenate, CoA and acetyl CoA decreased the rate of ethanol oxidation, where pantethine and sodium phosphopantothenate were competitive inhibitors, while CoA and acetyl-CoA inhibited the enzyme noncompetitively Ki = 1.2 x 10(-2) M, 2.1 x 10(-2) M, 4.4 x 10(-4) M and 5.1 x 10(-4) M, respectively. Metabolic precursors, which were different from pantothenic acid in their structure, were not involved in the alcohol dehydrogenase reaction. Possible regulation of alcohol intoxication using derivatives and precursors of vitamin B3 is discussed. PMID- 8511888 TI - [The effect of alcohol consumption on carboxypeptidase N activity in rat brain during chronic emotional-painful stress]. AB - With ethanol consumption, activity of carboxypeptidase H was increased in all the brain regions of rats with chronic emotional-painful stress. The most distinct increase of enzyme activity was found in the striatum membrane fraction and in the hippocampus. Carboxypeptidase H appears to be involved in development of stress reactions under conditions of ethanol consumption via the enkephalinergic system. PMID- 8511889 TI - [Lipids from gray and white rat brain matter in autolysis]. AB - A decrease in relative content of phospholipids and cholesterol simultaneously with increase in cholesterol esters and free fatty acids were detected in tissues of rat brain gray and white matters during autolysis at 37 degrees within 6-7 min, 1, 4 and 24 hrs; the most distinct alterations were observed in lipids of the gray matter especially at early (6-7 min) and late (24 hrs) stages of autolysis. In the gray matter, relative content of all the lipid fractions studied was restored to initial level within 4 hrs of incubation. In the white matter, during autolysis the content of cholesterol varied, the content of phospholipids was only slightly increased, while the level of free fatty acids was increased only at 24 hrs of incubation with synchronous decrease in content of triacylglycerols, cholesterol and, partially, phospholipids. These experimental data are of importance in resuscitation. Both common and dissimilar mechanisms of these lipid alterations are discussed. Not only the complex of hydrolase reactions but also that of transacylase and other reactions, involved in the degradation and biotransformation of brain lipids in autolysis, were noted. PMID- 8511890 TI - [Antioxidant components of erythrocytes and digestive secretions in childhood gastroduodenal diseases]. AB - Enzymatic and nonenzymatic components of the antioxidant system were studied in the erythrocytes, saliva and gastric juice of 20 healthy volunteers, 113 children with chronic gastroduodenitis and duodenal ulcerous disease. A decrease in the activity of superoxide dismutase and imbalance of the glutathione redox system were found both in the erythrocytes and the digestive secrets of children with gastroduodenal pathology. The rate of impairments depended on the gastric functional state, on the nature of disease development; the most pronounced alterations were detected in the gastric juice. PMID- 8511891 TI - [Level of certain carbohydrate components in blood serum and urine of patients at extensive periods since suturing for perforated gastroduodenal ulcers]. AB - The duration of gastric impairment before perforation as well as morphological features of sutured ulcer were shown to influence the protective functions of the gastric and duodenal mucosal membrane as shown by estimation of hexose, fucose and sialic acids in the blood serum and urine of 128 patients within later periods after suturing perforated gastroduodenal ulcers. Inhibition of the mucosal membrane protective functions in gastroduodenal tissues was increased with a longer disease period before perforation and with more distinct pathomorphological alterations of the perforated ulcer. PMID- 8511893 TI - [Phospholipid composition of rabbit liver mitochondria in moderately severe tracheal stenosis]. AB - A decrease in phosphatidyl cholines by 32.5%, phosphatidyl ethanolamines by 32.9%, cardiolipins by 28.8% and sphingomyelins by 48% as well as increase in concentration of phosphatidyl serine 4.2-fold, phosphatidyl inositol 4.1-fold, phosphatidic acid 10.3-fold and lysophosphatidyl cholines 2.7-fold were detected in liver mitochondria of rabbits with moderate tracheal stenosis. At the same time, the phosphatidyl choline/phosphatidyl ethanolamine ratio which is of importance in stabilizing membrane structures, was increased 1.5-fold. The ratio of diacyl forms of phospholipids and their lyso derivatives was also altered in stenosis of trachea: the phosphatidyl choline/lysophosphatidyl choline ratio was increased 4-fold. PMID- 8511892 TI - [The role of oligomeric structure of human serum albumin during its interaction with polyalbumin receptors in blood serum of patients with viral hepatitis B]. AB - Several oligomers of human blood serum albumin modified by glutaraldehyde differ in their binding ability to polyalbumin receptors in blood serum of patients with viral hepatitis B. Erythrocytes containing the albumin tetramer are able to agglutinate, while the red blood cells coated with dimer or monomer are deprived of this property. At the same time, the albumin dimers and monomers neutralize agglutination of the erythrocytes containing the complete pool of modified albumin in membranes although their effect is distinctly lower than that of tetramer. The albumin tetramer may have two or more sites of binding to erythrocytes or to the surface antigen of hepatitis B virus, bearing polyalbumin receptors, whereas the protein dimer or monomer contained only one site of binding. PMID- 8511894 TI - [Induction of Ca2+-dependent chemiluminescent response of peritoneal macrophages with bacterial lipopolysaccharides]. AB - A lipopolysaccharide preparation obtained from Klebsiella pneumonia was shown to affect primarily the peritoneal macrophages after intraperitoneal administration. Transition of the macrophages to a new metabolic state in response to opsonized zymosan was responsible for a distinct increase in the rate of luminol-dependent chemoluminescence. At the same time, the macrophages produced chemiluminescence was only slightly increased in the presence of Ca2+ ionophore A23187. These dissimilar alterations observed suggest that the primary reaction of macrophages in response to the lipopolysaccharide occurred with the increase in content of intracellular free calcium. Administration of finoptin (calcium influx inhibitor) into suspension of macrophages caused a decrease in the rate of chemiluminescence response. PMID- 8511895 TI - Clinical and experimental results as a basis of surgical practice. AB - Since John Hunter first applied the scientific approach to surgery in the late 18th century, it has been raised from the humble level of a handicraft to a highly experimental science. Although surgical research is essential, the practice of surgery has always been much influenced by the basic sciences. The clinical significance of experimental data has often only been recognized years later: research to no pre-defined end is also of utmost importance. Today, in a time of cost explosion and overabundance of information, cooperative and statistically well-planned studies are essential to optimize financial and physical resources. Fields of increasing interest such as gene technology, immunology and preventive medicine will influence surgery in the near future. Minimal invasive and interventional techniques have already started to revolutionize surgical practice. So surgical research today combines traditional medicine and modern techniques to put into practice immediately. If surgeons consider their field to be a unity of "craftsmanship, art and science" [10] and at the same time adhere to the rules of ethics, they will comply with the principle of "saluti et solatio aegrorum". PMID- 8511896 TI - [Value of surgery in treatment of complicated gastroduodenal ulcer]. AB - The surgical procedure in acute complications of gastroduodenal ulcers is examined with regard to risk factors and mortality. Emergency admissions to an Austrian district hospital between 1. 1. 1984 and 31. 8. 1992 for peptic ulcer are retrospectively analyzed. 293 patients were admitted with a history of bleeding ulcers. Endoscopic haemostasis was achieved in 91 of 130 (70%) patients with active haemorrhage (Forrest Ia, Ib). For the other 39 patients with active haemorrhage as well as for 16 of 65 patients with signs of previous bleeding (Forrest II) emergency surgery was necessary. 33 patients were admitted for perforated ulcers and all underwent emergency surgery. Distral gastric resections were performed in 98% of cases (54/55) with bleeding ulcers and in 91% of cases (30/33) with perforated ulcers. The surgically treated patients had a high percentage of accompanying illness and females were significantly older (mean 68 years) than males (55 years) (p < 0.01). Postoperative mortality was 9.1% (5/55) for bleeding peptic ulcers and 6.1% (2/33) for perforated ulcers. Furthermore, mortality was zero in patients younger than 60 years (0/44), but 15.9% (7/44) in patients older than 60 years. Distal gastric resection was chosen as standard procedure for emergency operations. PMID- 8511897 TI - [Milestones in Saxony medicine]. AB - This compilation refers to the achievements made over almost five centuries in Saxony. Particular reference is given to the universities of Leipzig, Dresden and Wittenberg. The reader may glean from this concise review what has been achieved in this period in the above region. PMID- 8511898 TI - [Right ventricular function in patients before and after lung transplantation]. PMID- 8511899 TI - [In vitro study with the excimer laser prepared corneal transplants]. PMID- 8511900 TI - [Endangerment of medicine by totalitarian basic principles]. AB - There are two different concepts of health which can be formulated: the abstract concept and the concrete concept. In the case of the abstract concept of health, illness appears as an evil which must be eliminated. Illness is not considered an integral part of a healthy organism. In the case of the concrete concept of health, the possibility that illness can occur is a necessary condition of being an organism. The structural connections between these concepts and totalitarian, political thinking will be discussed. PMID- 8511901 TI - [Brief definitions in medical ethics. Part 26. Technology assessment]. PMID- 8511902 TI - [The alcohol method for determining total body water: comparison with heavy water (D2O)]. AB - The determination of Total Body Water (TBW) by means of even dilution of the perorally administered indicator substance ethanol in the TBW-space is successful with a precision which is in direct comparison with other dilution-indicators, even superior that of D2O, which can be considered as a standard indicator substance for TBW. Thus, also indirectly, another proof emerges for the fact that ethanol dissolves exclusively in the body water. Applying the alcohol-method shows that even small changes of a few hundred milliliters of the body water volume, as they appear during the menstruation cycle, are detectable. Even in patients with a terminal renal failure and the risk of pathological water retention of several liters, there is no criterion which might exclude the TBW determination by means of the dilution of slight quantities of ethanol. Finally, considering the possibility to determine the blood alcohol concentration (after a complete distribution in the TBW-space) with sufficient precision using a breath ethanol analyzer of the latest generation, the possibility emerges to carry out TBW-determination in patients and volunteers essentially noninvasive. PMID- 8511903 TI - [Is improvement of the diagnostic value and reproducibility of stress ECG possible? Development of an ergometry score]. AB - Exercise stress test is the most widely used instrument in the detection of myocardial ischemia. We try to develop a score for objective and subjective symptoms occurring during this investigation. 428 stress tests are registrated, the parameters are documented, investigated according to a logical schema and data processed. PMID- 8511904 TI - [Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex(TAT) and thrombophilia parameters in orally anticoagulated patients with inferior vena cava filters]. AB - Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III-complex (TAT) levels were compared in 31 orally anticoagulated patients with inferior vena caval filters and a control group of 31 orally anticoagulated patients without caval filters and the incidence of markers of thrombophilia (deficiency of antithrombin-III, protein C, protein S and factor XII, presence of lupus anticoagulants) was determined. 8 of 31 patients (26%) from the group of caval filter carriers showed markers of thrombophilia (3 protein S deficiencies, 1 protein C deficiency, 2 factor XII deficiencies and 2 patients with lupus anticoagulants). In all orally anticoagulated patients a significant interdependence (p < 0.05) between F1 + 2- and TAT-levels and intensity (INR) of the oral anticoagulation could be observed. Comparison of F1 + 2- and TAT-levels of caval filter carriers and controls revealed no significant difference which leads to the conclusion that inferior vena caval filters do not induce detectable systemic activation of prothrombin under adequate oral anticoagulation therapy. PMID- 8511905 TI - [Preoperative monitoring of blood coagulation in urologic operations: diagnosis of familial factor XI deficiency within the scope of preoperative blood coagulation studies]. AB - Presurgical coagulation diagnosis should--apart from coagulation monitoring in the laboratory based on a stepwise diagnosis for detection of coagulations disorders, starting with global tests (NT/APTT) followed by appropriate specific investigation in case of pathological findings--consist of an adequate hemostaseological anamnesis and physical checkup of the patient. This would allow detection of important signs of hemostaseological impairment during the pre analytical phase already and permit subsequent initiation of more specific coagulation tests. The casuistics of a patient with factor XI-deficiency ("Minor Form"), a condition which is extremely infrequent in our country, demonstrates the coagulation diagnostic procedure which led to detection of his inherited factor XI-deficiency. In addition the pre-, peri- and postsurgical therapeutical management of this particular patient using an antifibrinolytic drug (tranexamic acid) is presented. PMID- 8511906 TI - World progress in surgery -- Metabolic changes in surgery. PMID- 8511907 TI - Metabolic basis for the management of patients undergoing major surgery. AB - After reviewing our current knowledge of the metabolic response to major abdominal surgery, we present two new studies in which we have followed the changes in body composition, physiologic function, and psychological function for up to 1 year after major surgery. In the first study, 46 patients had changes in body composition, physiologic function, and psychological function measured perioperatively and again at intervals up to 1 year. There was an average loss of weight of 3000 grams (maximum at 2 weeks), and the tissue composition of this weight loss was composed of 1400 grams fat, 600 grams protein, and 1000 grams water. Normal body composition had returned to normal in most patients by 6 months. In the second study of 84 patients, deficits of skeletal muscle function and fatigue were found to be greatest at postoperative day 7. Most patients were back to preoperative levels of muscle function and fatigue 30 days after surgery, and nearly all had normal values 90 days after surgery. Based on these studies we outline our management program for the metabolic care of patients undergoing major abdominal surgery. PMID- 8511909 TI - Underweight patients and the risks of major surgery. AB - The relation between weight loss and the risks of major surgery have been investigated for more than 50 years. It can now be said, with some confidence, that the underweight patient has an increased risk of complications following major surgery. This understanding, however, is based on methods of nutritional assessment that are of limited relevance to hospitalized patients whose malnutrition might be due to sepsis, neoplasia, trauma, or starvation. A consequence is the widespread belief that protein-energy malnutrition (PEM) has been overemphasized as a surgical risk factor, and that the many nonnutritional risk factors ought to be implicated more often. An argument is made for a fresh approach to nutritional assessment in order to better identify the individual patient who, by virtue of PEM, stands an increased risk of a complicated postoperative course. It is suggested that an evaluation of the impact PEM has on vital physiologic function provides a clinically relevant defect to identify and treat and a means of monitoring response to nutritional intervention. PMID- 8511908 TI - Metabolic basis for management of the septic surgical patient. AB - The physiologic events accompanying postoperative septic complications in surgical patients represent a coordinated response to bacterial invasion, which is aimed at maintaining the function of key organ systems. When sepsis is prolonged or overwhelming, physiologic dysfunction and multiorgan failure develop. This review outlines the pathophysiologic response to sepsis and correlates it with recent therapeutic advances in the metabolic management of the postoperative septic patient. PMID- 8511910 TI - Overview of randomized clinical trials of total parenteral nutrition for malnourished surgical patients. AB - The past decade has seen a maturation of the art and science of perioperative nutritional support. We now have sufficient data to make informed and reasonable judgments regarding when we should and should not provide perioperative TPN. These judgments can be considered medically sound and fiscally responsible. The following guidelines are proposed: (1) Postoperative TPN should be considered when oral or enteral feeding is not anticipated within 7 to 10 days in previously well-nourished patients or within 5 to 7 days in previously malnourished or critically ill patients. (2) Preoperative TPN should be considered in patients who cannot or should not eat or receive enteral feedings if the operation must be delayed for more than 3 to 5 days. (3) Preoperative TPN should be considered in the most severely malnourished surgical candidates if an operative delay is not contraindicated. In patients with only mild to moderate degrees of malnutrition preoperative TPN is not indicated. PMID- 8511912 TI - Preparation of the intensive care patient for major surgery. AB - Improved methods for monitoring and treating critically ill patients have increased the number of surgical candidates with multiorgan system impairment. Whereas such patients may have been considered "too sick to undergo surgery" in the past, many such patients linger in the intensive care unit unless definitive therapy is accomplished. Specific attention to review of the patient's preoperative preparation for surgery on a system-by-system basis may improve outcome substantially. The need for possible mechanical ventilation prior to transport to the operating room must receive particular attention. Pneumothorax, if present, must be treated prior to institution of positive-pressure ventilation so progression to tension pneumothorax can be avoided. Deficits in the circulating blood volume must be identified and corrected preoperatively if possible. A need for enhancement of cardiac output or alteration of vascular tone requires pulmonary arterial catheterization and indicates an increased operative risk. Metabolic abnormalities such as disturbances of acid-base balance, sodium or potassium concentration, and endocrinopathies are identified and corrected as much as possible prior to operation. Antibiotics are instituted as appropriate. Replacement of the red blood cell mass is dictated primarily by anticipated or actual blood loss. Factors of coagulation are infused on a replacement basis as necessary. Great care must be taken during transport to the operating room, as maintenance of intravascular monitoring devices, therapeutic infusions, and mechanical ventilation must continue during transport. Precautions must be taken to avoid hypothermia during transport and institution of anesthesia. Critical illness mandates specific considerations of the anesthetic agents to be utilized. PMID- 8511911 TI - Prophylaxis against sepsis in patients undergoing major surgery. AB - Postoperative infection in general surgical patients is discussed according to operation types. A selection of the huge literature on each group is reviewed, and details from the author's own work and ideas are presented. By discussing these points attempts are made to determine the best regimens for a given set of clinical circumstances. There is a small literature indicating that postoperative chest infection can be prevented by some antibacterial drug regimens, and this question has been addressed; it seems that in the past it has been largely ignored. Some nonantibacterial methods of reducing postoperative infection are also briefly discussed. PMID- 8511913 TI - Perioperative care of the elderly patient. AB - Surgical risk increases with age, primarily from loss of cardiac and pulmonary reserve. Complications are tolerated poorly by the elderly, emphasizing the importance of their prediction and prevention. Surgical risk in this population is significant, but with careful preoperative assessment and perioperative management acceptable morbidity and mortality are possible. This review proposes a general approach to the elderly surgical patient and applies it to the most significant sources of morbidity and mortality: pulmonary and cardiac complications. Risk assessment based on validated tools is utilized, and perioperative management recommendations based on the state of the art are examined. In addition, pulmonary embolism and postoperative confusion are examined separately with the same overall strategy. PMID- 8511914 TI - Perioperative care of the oncology patient. AB - Cancer patients are often at high risk for perioperative complications because of preexisting conditions, the magnitude of surgery, and the use of aggressive multimodality treatment. It is essential to identify risk factors preoperatively, correct any deficits, and monitor organ dysfunction. During the perioperative period prophylaxis and surveillance for cardiopulmonary, hematologic, and septic complications should minimize morbidity and mortality. Finally, nutritional support should be given to malnourished patients undergoing extensive operative procedures. PMID- 8511916 TI - Postoperative pain. AB - Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree of surgical expertise and use of other perioperative therapeutic interventions including nutrition and mobilization, should be combined to improve overall perioperative care and surgical outcome. PMID- 8511915 TI - Perioperative care of the immunocompromised patient. AB - Immunocompromised patients are increasingly common in modern surgical practice. Challenges related to their care include identifying the determinants of increased risk and selecting the appropriate therapy for individual patients. There are multiple and overlapping causes of immunosuppression in surgical patients that make the interpretation of clinical trials difficult. A clear understanding of these mechanisms guides the physician to choose the immunomodulatory agents that can be used for improving current rates of complication and mortality. The best practical approach to immunocompromised patients involves determining who is at risk, aggressive diagnosis, early therapy, and a high index of suspicion for infectious complications. PMID- 8511917 TI - Postoperative fatigue. AB - Uncomplicated major surgery is followed by a pronounced increased feeling of fatigue extending throughout the first month in about one-third of patients. Postoperative fatigue correlates with the degree of surgical trauma but is not related to duration of general anesthesia and surgery or to preoperative nutritional status, age, or sex. Fatigue also correlates with postoperative deterioration in nutritional parameters and impaired adaptability of heart rate during exercise. Furthermore, a postoperative decrease in muscle force and endurance is related to postoperative fatigue, whereas psychological factors are of minor importance. These findings suggest postoperative fatigue to be mediated by the endocrine-metabolic response to surgery, impaired nutritional intake, or immobilization, but the relative role of these factors remains to be established. Until then, therapeutic measures against the development of postoperative fatigue should aim at reducing the surgical stress response, effective treatment of pain to facilitate mobilization, and exercise to increase postoperative nutritional intake. PMID- 8511918 TI - Predicting postoperative fatigue: importance of preoperative factors. AB - Postoperative fatigue as defined by a 10-point scale (1 = fit, 10 = fatigued) was determined prospectively in 84 patients undergoing major surgery. Results from this scale correlated well with standard psychological assessment of fatigue (Profile of Mood States Questionnaire) (r = 0.767; p < 0.0001). Fatigue values were 3.46 +/- 0.19 arbitrary units (mean +/- SEM) preoperatively; and postoperatively they were 5.61 +/- 0.24 at day 7, 5.02 +/- 0.24 at day 14, 3.74 +/- 0.19 at day 28, and 2.77 +/- 0.18 at day 90. Fatigue during the postoperative period was integrated to give a total fatigue score (332 +/- 14 arbitrary units, range 90-664), and this score was correlated with preoperative and early postoperative factors. The best predictor of postoperative fatigue was preoperative fatigue (r = 0.545; p = 0.001), with lesser correlations with diagnosis (especially cancer); preoperative weight, particularly total body protein (r = 0.317; p = 0.01); and weight loss (r = 0.29; p = 0.03), grip strength (r = 0.352; p = 0.01), and age (r = 0.267; p = 0.01). Postoperative fatigue was not correlated with preoperative anxiety, depression, or hostility, involuntary muscle function, gender, preoperative stress, or changes in total body protein or fat over the two postoperative weeks. It is concluded that patients who present for surgery already fatigued are the ones who are most likely to suffer from prolonged postoperative fatigue, particularly so if they are elderly, suffer from cancer, or have few extra reserves of body protein. PMID- 8511919 TI - Occupational risk to surgeons of unrecognized HIV infection in a low-prevalence area. AB - Data are available on the occupational risk to surgeons of the human immunodeficiency virus (HIV) for areas of high HIV prevalence but not for low risk areas and particularly for unrecognized HIV infection. The 40-year cumulative occupational risk to surgeons caring for patients with unknown HIV serologies in a low-prevalence area was estimated. From May 1989 to May 1991, 4119 consecutive patients with unknown HIV status, hospitalized in our department, were proposed for testing; 100% complied. Acquired immunodeficiency syndrome (AIDS) patients and known seropositive patients operated on during this period were excluded from the study. The prevalence of unknown HIV infection was 0.07%. Taking into account the rate of parenteral injuries, the rate of contamination after an infected parenteral injury, and the total number of operations performed during a 40-year career, we estimated the cumulative risk of unknown HIV infection in our area to be 1%. This risk must be added to those of caring for known infected patients. In high-risk areas (cumulative risk 10%), a high standard of infection control is required for every surgical procedure, even if it is expensive or of doubtful efficacy. It is unrealistic to apply this standard in a low-risk area. HIV testing with informed consent of the patient is an imperfect guard against infection but has the advantage of alerting the surgeon to the risk of contamination on a case-by-case basis; it also offers the seropositive patient the best possibility for a longer life expectancy. PMID- 8511920 TI - Postmastectomy morbidity after combination preoperative irradiation and chemotherapy for locally advanced breast cancer. AB - Neoadjuvant therapy for locally advanced breast cancer improves disease control, but the complications of treatment are not well established. The aim of this study was to assess the operative morbidity in 20 consecutive patients with locally advanced, noninflammatory breast cancer treated with preoperative chemotherapy and radiation. Patients received preoperative cyclophosphamide, methotrexate, 5-fluorouracil, prednisone, and tamoxifen (CMFPT) to maximum response followed by concurrent chemotherapy and radiation to the involved breast and regional lymph nodes. Following modified radical mastectomy, chemotherapy was continued for a total of 10 cycles. Disease progressed in 3 of 20 patients (15%). Seventeen patients underwent mastectomy, 4 (24%) of whom demonstrated a pathologic complete response to chemoradiotherapy. Seven patients (41%) developed wound infections, 2 (12%) necrosis, 5 (29%) delayed healing, 2 (12%) upper extremity lymphedema, and 8 (47%) seromas. Postoperative chemotherapy was delayed in 4 (24%) patients. There was no mortality, and hospitalization was for less than 1 week. Only one patient required readmission. Although this treatment regimen is aggressive with attendant morbidity, complications are easily managed and generally do not delay therapy. Treatment modification to further reduce complications may be indicated. PMID- 8511921 TI - Appendicitis diagnosis today: clinical and ultrasonic deductions. AB - A total of 111 patients referred with a diagnosis of suspected "appendicitis" were entered into a prospective study. The surgeon and radiologist in charge of ultrasonography made separate diagnoses, and their findings were then combined and discussed as indications for surgery. Clinically, a history of pain migration proved to be reliable (p < 0.0001) as a diagnostic indicator, in contrast to nausea and initial irregularity of bowels. The duration of symptoms was significantly shorter in patients with proved appendicitis than among patients with negative findings (median 24 hours compared with 41 hours, p < 0.04). Among patients with perforated appendicitis, the symptomatic history was prolonged (not significantly) by 3 hours. Peritoneal signs such as pain on percussion, rebound tenderness, guarding, and a leukocytosis of more than 13,000/mm3 were indicative of appendicitis (p = 0.0001 for each sign). Lively bowel sounds excluded the possibility of appendicitis (p = 0.001). Scanty bowel sounds, rectal tenderness, axillorectal temperature difference, and a left shift in leukocytes were of no diagnostic significance. The doctor's "clinical experience" is significant at the level of p < 0.03. On ultrasonography, the following signs were indicative of appendicitis: periappendicular infiltration (p = 0.0003), a visible "cockade," and an appendix larger than 12 mm in diameter (p = 0.04). For 75% of the patients the surgeon was sure of his own clinical diagnosis and did not allow himself to be influenced by the sonographic findings. In 12% of doubtful cases ultrasonographic results decisively favored operation, and in 4.5% (n = 5) it prevented an unnecessary laparotomy in the presence of positive clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511922 TI - Logistic regression and discriminant analyses of hepatic failure after liver resection for carcinoma of the biliary tract. AB - Stepwise logistic and discriminant analyses were used to define the risk factors for hepatic failure after liver resection for carcinoma of the biliary tract and to predict this complication. The logistic analysis identified the linear pattern of oral glucose tolerance test, cholangitis, pancreatoduodenectomy, and indocyanine green disappearance rate as the factors most related to hepatic failure among 18 pre- and perioperative parameters of the past 84 hepatectomized cases (55 hilar bile duct carcinomas and 29 gallbladder carcinomas). Our discriminant formula using five variables, including the above-mentioned four plus the liver resection rate, could distinguish the patients with posthepatectomy liver failure (n = 25) from those without (n = 59) with 86.9% accuracy, 96.0% sensitivity, and 83.1% specificity. The cross-validation test has confirmed that this model was robust for discriminant analysis. The results of this study show that statistical multifactorial analysis makes possible the preoperative prediction of hepatic failure after liver resection for carcinoma of the biliary tract. PMID- 8511923 TI - Neoadjuvant chemotherapy for high-grade advanced gastric cancer. AB - Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5 fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered. PMID- 8511924 TI - Laparoscopic cholecystectomy: treatment of choice for cholelithiasis in children. AB - Laparoscopic cholecystectomy is rapidly replacing traditional cholecystectomy as the standard treatment for cholelithiasis and cholecystitis in adults. Over a period of 16 months, 14 children with a clinical diagnosis of cholelithiasis, ranging in age from 4 to 15 years (mean 12.2), were treated. All had symptoms of abdominal pain or vomiting; one had jaundice and recurrent cholecystitis. Five children (35%) had associated metabolic or hemolytic diseases. The 14 children were operated on using the laparoscopic cholecystectomy technique. No operation was converted to open cholecystectomy, but two patients required laparotomy: one because of suspected injury to the common duct, and the other because of nonvisualization of the gallbladder during laparoscopy. The mean post-operative hospital stay for the 11 children who underwent only laparoscopic cholecystectomy (one patient also had a simple mastectomy) was 50 hours (range 48-72 hours). All children resumed their normal activities almost immediately after discharge from hospital. No long-term biliary or other complications were seen in any patient throughout an average follow-up period of 6.2 months (range 3-16 months). The benefits of this operation in children are obvious: It is safe, effective, and well tolerated. PMID- 8511925 TI - Colon J-pouch rectal reconstruction after total or subtotal proctectomy. AB - Multiple stools, urgency, and episodic frequency are common during the first 6 months after proctectomy and coloanal or low colorectal reconstruction. We used an 8-cm colon J-pouch in 23 patients and have confirmed that this approach obviates much of this early dysfunction. PMID- 8511928 TI - Of health care and waterfowl. PMID- 8511926 TI - Endorectal ultrasonography for staging small rectal tumors: technique and contribution to treatment. AB - Thirty-one tumors, lying in the lower two-thirds of the rectum and possibly suitable for local excision, were analyzed by endorectal ultrasonography (EUS) using the Aloka scanner SSD 520. There were 18 sessile villous adenomas (group I) and 13 invasive cancers 3 cm or less (group II). Preoperative endosonographic staging (uT, uN stages) was compared with the histologic analysis of the specimens (pT, pN) and the possible contribution to therapy was evaluated. In group I, the depth of tumor infiltration was accurately assessed in 89% of cases. Malignant transformation was suspected in 4 cases (uT2) and confirmed postoperatively in 3 cases. In group II, the extent of the tumor was correctly evaluated in 84% of cases. With regard to the overall differentiation between T1 and T2/T3 tumors on one hand, and between T1/T2 and T3 lesions on the other hand, the positive predictive values were 93.3% and 100%, respectively. The negative predictive values were 93.7% and 92.8%. In group II the search for regional lymph nodes was positive in 4 cases and negative in 9 cases. An accuracy rate of 82% (sensitivity 75%, specificity 85%) was estimated by analysis of the specimens and postoperative follow-up. The exact performance could not be evaluated because a radical resection was not carried out in most cases. EUS was useful for planning the treatment of villous adenomas. A board full-thickness excision was carried out without delay for the four uT2 villous tumors, allowing safe margins to be obtained in all cases. Using EUS the choice of local excision was questioned for six small invasive cancers (uT3 and/or uN+), although radical resection was carried out for only two. As high sensitivity could not be achieved when detecting lymphatic metastasis, the choice of limited surgery based on EUS staging requires strict postoperative follow-up. PMID- 8511927 TI - Acute temporary laterofixation for treatment of bilateral vocal cord paralyses after surgery for advanced thyroid carcinoma. AB - Four patients with breathing obstruction after surgery for advanced thyroid carcinoma were found to have bilateral vocal cord paralysis. They were treated with acute temporary laterofixation of one of the vocal cords. This measure established a stable airway in all the patients and maintained acceptable voices. None of the patients had aspiration problems. After 4 to 7 weeks the nonlaterofixated vocal cord had regained normal function in each patient, and the thread used for the laterofixation could be removed. In the two patients who had anatomically intact recurrent laryngeal nerves bilaterally, the previously laterofixated vocal cords displayed normal movements within another 8 weeks in one patient and 7 weeks in the other patient. This observation demonstrates that a temporary laterofixation can be done without lasting damage to the vocal cord. Acute temporary vocal cord laterofixation is a procedure that has the potential to minimize the morbidity and complications of bilateral vocal cord paralysis, and in most patients it can be done instead of tracheostomy. PMID- 8511929 TI - EVP report: the view from here. Problems of supply and demand. PMID- 8511930 TI - Who is the victim? PMID- 8511931 TI - A 354-gram infant: 48 month follow-up. AB - Extreme prematurity (birth weight less than 500 g) with intact survival is very uncommon. This paper describes a preterm infant with birth weight of 354 g who is now 4 years old and developmentally normal. Intervention and management decisions in such a low birth weight group produce an ethical enigma. Survival of newborns with a birth weight less than 400 g is unusual. Decisions regarding intervention and care for extremely low birth weight infants impact on financial, emotional, and medical responsibilities of family members and health care professionals. It has been increasingly difficult to set guidelines or policies regarding resuscitation of "micropremies" based on weight and gestational age. PMID- 8511932 TI - An overview of a study on the financial viability of clinics and physician practices in medically under-served areas of Wisconsin. AB - A survey of 21 physicians and clinic managers located in Health Professional Shortage Areas (HPSAs) and other under-served areas in Wisconsin found that to combat increasing costs, Medicare and Medicaid discounts, charity care demands and physician recruitment difficulty, several practices rely on outside sources of funding to remain financially viable. Also, the financial viability of physician practices in under-served areas of Wisconsin is threatened more by the reimbursement rates of Medicaid and Medicare than by the provision of charity care. Though few are limiting the number of Medicare and uninsured patients they will treat, many have begun implementing cost-containment measures, including more strict collection policies. There are also indications of restricted access for Medicaid patients at some sites. PMID- 8511933 TI - Wisconsin physicians sue Minnesota over provider tax. PMID- 8511934 TI - New AIDS definition increases reported cases; physicians asked to review records. PMID- 8511935 TI - Child and adolescent cigarette smoking and consumption. PMID- 8511936 TI - Youth access to tobacco products: protocol for conducting compliance checks. PMID- 8511937 TI - Physicians' attitudes toward nursing home practice in Milwaukee. PMID- 8511938 TI - [Selection of patients with chronic hepatitis B for therapy with alpha interferon]. PMID- 8511939 TI - [Current clinico-immunologic aspects of Sjogren syndrome]. PMID- 8511940 TI - [Diagnostic errors in symptoms of endocrinologic diseases]. PMID- 8511941 TI - [Knee joint arthroscopy as ambulatory operation]. PMID- 8511942 TI - [Life without bread]. PMID- 8511943 TI - [Dietary aspects and nutritional guidelines in kidney diseases]. PMID- 8511944 TI - [Survival of diabetic patients at 30-year follow-up with reference to a closed population]. PMID- 8511945 TI - [Unusual complication of aortic valve replacement surgery--a case report]. PMID- 8511946 TI - [Acute pancreatitis and pregnancy. Discussion of etiology and pathogenesis based on a case report]. PMID- 8511947 TI - [A case from general practice (8): tetany and diarrhea]. PMID- 8511948 TI - [From the files of an expert assessment service: a lump in the breast unless proven otherwise is suspected cancer]. PMID- 8511949 TI - [Jewish physicians in Berlin]. PMID- 8511950 TI - [Approaches to diagnosis of alcohol dependence]. AB - In a basic part are discussed: aims of the diagnosis, psychological and somatic dependence, psychological defence of the reality of dependence, the estimation of alcoholism and its "severity", the alcohol dependence syndrome and approaches to a multidimensional diagnosis. A second part deals with single diagnostic methods. Combinations out of self-statements of the probands and medical results provide a differentiated diagnosis. PMID- 8511952 TI - [Religious dogmatism and ecclesiogenic neuroses. A quasi-experimental contribution to Catholic church communities between tradition and pleuralism]. AB - Schaetzing (1955) characterizes "ecclesiogen neurosis" as mental disturbances, which are caused by "dogmatism of the church". To prove his thesis that the factor "dogmatism of the church" goes along with ecclesiogen-neurotic symptoms we use as factorial levels two different forms of Catholic congregations, that is to say a "traditional congregation" (high "dogmatism of the church") and a "pluralistic" one (low "dogmatism of the church"). In this quasi-experimental design 93 Catholics who are involved in the church of a "traditional" congregation and 70 of a "pluralistic" one are examined. The correctness of categorizing these congregations to the factorial levels is proved empirically. To record ecclesiogen-neurotic symptoms we consider "religious anxiety" (Kim, 1988) and "depressivity" (Zerssen, 1976). Our findings show that active Catholics of both congregations show a distinct higher expressivity in the dependent variable "depressivity" compared with the mean population. The comparison of both congregation samples by analysis of covariance shows furthermore, that the dependent variable "religious anxiety" is significantly higher in the "traditional" congregation than in the "pluralistic" one. The results are later critically discussed. PMID- 8511951 TI - [A concept of social support for acute schizophrenic patients. Time series analysis of daily fluctuations of psychotic markers]. AB - Findings of 12 single case studies which documented and analyzed the course of features typical in an acute psychotic episode during a milieu-therapeutic treatment are reported (criteria: DSM-III-schizophrenia). Three different stages in treatment are distinguished (relaxation-activation-integration). Each stage can be described as a decrease in stimulus protection with a concurrent continual increase in psychosocial demands. The purpose of this study is to verify whether stable differences in psychotic characteristics exist between the disparate stages, and whether stage assignment is sensitive to changes in psychotic features. The results of the statistical data analysis according to the ARIMA intervention-model demonstrate a significant reduction in psychotic features in relation to treatment stages (10 and 8 out of 12 time series respectively). Hypothetical changes were specified as starting abruptly and as being permanent. PMID- 8511953 TI - [Temperament, psychological development and psychopathology. Correlations, explanatory models and forms of intervention]. AB - A return to temperamental concepts characterizes contemporary child psychology in the United States. The word "temperament" refers to early developing differences in reactivity and behavioral style. Temperament research focuses on the origins, the stability, the dimensionality and the psychopathological significance of such differences. This article especially emphasizes the latter. Associations between temperament and psychopathology are noted. Chess' and Thomas' goodness of fit model is presented as an explanatory model for these associations. According to this model, behavior disorders result from an incompatibility between the normal variations of child and environment. The applicability of this model in clinical and educational settings is then outlined. Finally, the author considers the contribution of temperament research to established paradigms in developmental psychopathology. PMID- 8511954 TI - [Psychosomatic and somatopsychic aspects of myasthenia gravis. A critical review of the literature]. AB - In an extensive literary abstract the up to now existing scientific research strategies and results concerning the psychosomatics of myasthenia gravis are introduced. While the pioneers of myasthenia-research already registered psychological disorders that were separated from differential diagnostic conversion neurosis, new studies show the noticeable high prevalence of psychopathological symptoms in myasthenia-patients. Besides monistic-somatic models, psychosomatic attempts of explanation were put forth in the past. Authors seem to agree at least with regard to psychological factors being able to influence symptom manifestation and course on a casuistic basis. Somatopsychic interdependencies seem to be of more significance, as it is stressed by coping research. However controlled longitudinal studies lack yet, so far as to what degree psychosocial and somatic factors are clinically relevant with regard to coping with the disease. Perspectives for future research are given finally. PMID- 8511955 TI - [Coping with illness by dialysis and tumor patients]. AB - In the present article the coping of cancer-patients and patients with chronic renal failure is analysed and compared with each other. We isolated a pattern of strategies that was rated high by the patients, either in their own appraisal or reported by them freely. We describe the most rejected contents, the strategies of defence (threat-regulation), and also the individually experienced main impairments of the diseases. Although we analysed two different groups of illnesses, we have not been able to differentiate the respective coping patterns. The fact that the patients preferred the same strategies and rejected the same ones was a surprising outcome! The only differences were found in the freely reported impairments of the diseases. Within the group of cancer-patients we found heterogeneous strategies of defence (threat-regulation), a fact that points to the necessity of particular analysis in the research of coping. PMID- 8511956 TI - [Illness concepts of children: an overview of current research]. AB - The present paper tries to summarize the main research topics on concepts of children about health and illness. The present research in this area is allocated to two theoretical positions: (a) cognitive-structural and (b) knowledge related research orientations. After describing the theoretical positions the paper turns to consequences of illness-related conceptions for the experiencing and behaviour of children. The main topics are interactions between illness-related conceptions and emotional experiences and relations of illness-related conceptions to behaviour (compliance, coping and preventive behaviour). The final sections are related to consequences of the present research results for dealing with children. PMID- 8511957 TI - [Biographical structure of illness and recovery processes. The recovery history of a women with epilepsy]. AB - Medical treatment generally focuses on the elimination of symptoms. This study of an epileptic woman documents the importance of taking the patient's entire biography into consideration in order to attain a full understanding of the illness. The healing process, accordingly, is not an attempt to repress the symptoms by means of medical treatment. Instead the patient works through her life history, beginning with group therapy over an extended period; this process finally leads to psychic and clinical recovery. The regaining of psychic viability and the forming of future perspectives prove to be particularly important moderators in the recovery process. PMID- 8511958 TI - [Schottlaender's heritage and psychoanalysis today]. AB - Felix Schottlaender (1892-1958), one of the founders of the Stuttgart Institute for Psychotherapy, developed an original conception of psychic illness and cure. This conception is presented and its relevance for the actual psychoanalytic discussion is valued in five points: (1) The role of the mother, (2) ego psychology, (3) "blinding by images", (4) personal encounter in psychotherapy, (5) basic philosophical questions of psychoanalysis. PMID- 8511959 TI - [Empirical study of a physically oriented therapy with schizophrenic patients]. AB - Ten predominantly chronic schizophrenics were given body therapy, including massage to the feet, back and neck. The aim of the therapy was to increase patients' awareness of their own bodily limits. This objective is based on the view that schizophrenia is a problem of delimitation, that psychic problems have their physical embodiment, and that problems of delimitation can therefore be tackled at the physical level by enhancing the patients' ability to experience their own bodily limits. The relaxing effect of the therapy is indicated in physiological measurements of skin conductance and heart rate, plus patients' self-perceptions. The close physical presence of the therapist did not trigger any anxiety conditions. The study shows that this body-oriented therapy is worthy of consideration as a method for giving schizophrenic patients a greater awareness of their own bodily limits. PMID- 8511960 TI - [Evaluation of paradoxical interventions]. AB - In anecdotal, uncontrolled case reports the threats to internal and external validity cannot be ruled out and the drawing of valid conclusions are prevented. These limits the usefulness of the "impressive" results of anecdotal case reports of paradoxical interventions. The few of controlled single case experimental and group designs permit valid conclusions and prove the efficacy of paradoxical interventions, but not their general superiority over other treatments. Meta analysis also point to efficacy but not to the superiority of paradoxical interventions over other procedures. The combinations of paradoxical and behavioral procedures seem to enhance efficacy. What is missing in paradoxical treatment studies is the clear and detailed description of the specific interventions as well as the proof of the treatment's integrity. What is still unclear is the range of indications for paradoxical interventions, the clients' satisfaction and acceptability of the paradoxical interventions and ethical issues. PMID- 8511961 TI - [Discrete motor and sensory disorders (neurologic soft signs) in the acute course of endogenous psychoses]. AB - Neurological soft signs (NSS) were investigated in 67 patients with DSM-III schizophrenia (remitting course, n = 23, chronic course, n = 27) and affective psychosis (n = 17). Patients were examined on admission, 7 days later and before discharge when being in a stable condition. In all diagnostic groups the NSS scores varied in the clinical course with a significant decline towards discharge. The variation of the NSS in the clinical course was further investigated with respect to psychopathological and clinical variables. Significant correlations between NSS, thought disorders, negative symptoms and a worse premorbid adaptation were found. To characterize NSS more precisely, all subjects executed a battery of standard neuropsychological tests on discharge. This step revealed significant correlations between NSS, graphomotoric and mnestic performance, the subscale "thought processes" of the Tubinger Luria Christiansen Scale and--to a lower extent--attentional performance. Our study provides two major findings: first, NSS vary in the clinical course and second, NSS are associated with other neuropsychological, such as mnestic and attentional, disorders. Thus, one may hypothesize, that NSS do not only reflect a primary motoric and sensoric deficiency but may be characterized as heterogeneous phenomena which occur frequently in the clinical course of endogenous psychosis. PMID- 8511962 TI - Phylogenetic study of ribosomal DNA of cactophilic Pichia species by restriction mapping. AB - The rDNAs of strains of the cactophilic Pichia species P. amethionina, P. antillensis, P. barkeri, P. cactophila, P. caribaea, P. deserticola, P. heedii, P. kluyveri, P. norvegenesis, P. opuntiae, P. pseudocactophila, P. thermotolerans and their varieties and anamorphs were mapped with 15 restriction endonucleases, and compared to P. membranaefaciens and P. salictaria as possible non-cactophilic relatives. The existence of species complexes among those taxa was confirmed. P. membranaefaciens was a plausible ancestral species, and its closest relative in the cactophilic group was P. deserticola. These two species appeared to be moderately related to P. heedii and to P. barkeri, but the latter was shown clearly to belong to the P. kluyveri complex, in spite of a 6 mol% G+C difference in their nuclear DNAs. P. cactophila and P. pseudocactophila ostensibly emerged from P. norvegensis, a facultatively cactophilic yeast. The P. amethionina, P. cactophila and P. opuntiae species complexes appeared independent from one another and from all other species studied. P. salictaria did not appear to be related to P. amethionina. PMID- 8511963 TI - Peroxisomal amine oxidase of Hansenula polymorpha does not require its SRL containing C-terminal sequence for targeting. AB - Amine oxidase (AMO) is a peroxisomal matrix protein of Hansenula polymorpha, which is induced during growth of the yeast in media containing primary amines as a sole nitrogen source. The deduced amino acid sequence of the protein contains an SRL sequence at nine amino acids from the C-terminus. In this study, we have examined the possible role of the SRL motif in sorting of AMO to peroxisomes by mutating the corresponding gene sequence. For this purpose, we have developed a DNA construct that is specifically integrated into the AMO locus of the H. polymorpha genome, placing the mutant gene under the control of the endogenous AMO promoter and eliminating expression of the wild-type gene. Analysis of a stable transformant, containing the desired gene configuration, showed that mutation of the C-terminal sequence neither interfered with correct targeting of the protein into the peroxisome nor displayed significant effects on its activity. From this, it was concluded that the SRL-containing C-terminus is not essential for peroxisomal targeting of AMO in H. polymorpha. PMID- 8511964 TI - Control of Saccharomyces cerevisiae carboxypeptidase S (CPS1) gene expression under nutrient limitation. AB - Expression of the vacuolar carboxypeptidase S (CPS1) gene in Saccharomyces cerevisiae is regulated by the availability of nutrients. Enzyme production is sensitive to nitrogen catabolite repression; i.e. the presence of ammonium ions maintains expression of the gene at a low level. Transfer of ammonium-glucose pre grown cells to a medium deprived of nitrogen causes a drastic increase in CPS1 RNA level provided that a readily usable carbon source, such as glucose or fructose, is available to the cells. Derepression of the gene by nitrogen limitation is cycloheximide-insensitive. Neither glycerol, ethanol, acetate nor galactose support derepression of CPS1 expression under nitrogen starvation conditions. Non-metabolizable sugar analogs (2-deoxyglucose, 6-methyl-glucose or glucosamine) do not allow derepression of CPS1, showing that the process is energy-dependent. Production of carboxypeptidase yscS also increases several-fold when ammonium-pregrown cells are transferred to media containing glucose and a non-readily metabolizable nitrogen source such as proline, leucine, valine or leucyl-glycine. Analysis of CPS1 expression in RAS2+ (high cAMP) and ras2 mutant (low cAMP) strains and in cells grown at low temperature (23 degrees C) and in heat-shocked cells (38 degrees C) shows that steady-state levels of CPS1 mRNA are not controlled by a low cAMP level-signalling pathway. PMID- 8511965 TI - Molecular genetics in Saccharomyces kluyveri: the HIS3 homolog and its use as a selectable marker gene in S. kluyveri and Saccharomyces cerevisiae. AB - We cloned the Saccharomyces kluyveri HIS3 homolog, k-HIS3, and made a partial deletion of the gene. The k-HIS3 gene complemented a HIS3 deletion in S. cerevisiae. The DNA sequences of the open reading frames (ORFs) of the HIS3 homologs are 70% identical at the DNA level and 83% identical at the deduced amino acid level. The ORF upstream of the k-HIS3 gene is related to the PET56 gene of S. cerevisiae found upstream of the HIS3 gene of S. cerevisiae. The ORF downstream from the k-HIS3 gene is not related to the DED1 gene found downstream of the HIS3 gene in S. cerevisiae. PMID- 8511966 TI - Physical localization of yeast CYS3, a gene whose product resembles the rat gamma cystathionase and Escherichia coli cystathionine gamma-synthase enzymes. AB - We have cloned, sequenced and physically mapped the CYS3 gene of Saccharomyces cerevisiae. This gene can complement the cys3-1 allele, and disruptions at this locus lead to cysteine auxotrophy. The predicted CYS3 product is closely related (46% identical) to the rat cystathionine gamma-lyase (Erickson et al., 1990), but differs in lacking cysteine residues. These results provide further evidence that the S288C strain of yeast resembles mammals in synthesizing cysteine solely via a trans-sulfuration pathway. The CYS3 product was found to have strong homology to three other enzymes involved in cysteine metabolism: the Escherichia coli metB and metC products and the S. cerevisiae MET25 gene product. The trans-sulfuration enzymes appear to form a diverged family and carry out related functions from bacteria to mammals. PMID- 8511967 TI - Yeast flocculation: lectin synthesis and activation. AB - Yeast flocculation involves binding of surface lectins to carbohydrate receptors on neighbouring cell walls. Brewing strains of Saccharomyces cerevisiae normally become flocculent in the stationary phase of growth. This paper presents evidence that lectins are synthesized in exponential phase, inserted into the cell wall, and activated later at the time of flocculation onset. Cycloheximide failed to prevent flocculation unless it was added in early growth; with later additions progressively larger degrees of flocculation occurred. Flocculation onset was delayed by cycloheximide but was otherwise cycloheximide insensitive. Preflocculent cells could be artificially activated to full flocculation by heat. Artificial activation of samples from growing yeast cultures confirmed the progressive synthesis of lectins throughout exponential growth. Pronase E treatment of whole cells prior to heating prevented any activation of flocculation. It was concluded that lectins were synthesized continuously from an early stage of growth and rapidly inserted into the cell wall (accessible by pronase E), where they remained inactive for up to 14 h, before being activated at flocculation onset by an as-yet unknown mechanism. It was found that lectin synthesis and activation occurred in all brewing strains tested. PMID- 8511968 TI - Secretion of mouse alpha-amylase from fission yeast Schizosaccharomyces pombe: presence of chymostatin-sensitive protease activity in the culture medium. AB - We have constructed two secretion vectors for Schizosaccharomyces pombe using an SV40 promoter and the secretion signals of the pGKL killer toxin complex derived from Kluyveromyces lactis. Although indigenous secretory glycoproteins tend to accumulate in the periplasmic space of S. pombe, we have succeeded in the secretion of mouse alpha-amylase into the culture medium. The efficiency of secretion, processing pattern, stability and culture conditions for mouse alpha amylase were studied in S. pombe. The 128 kDa killer secretion signal was more effective in directing secretion of mouse alpha-amylase than the 28 kDa killer secretion signal. We detected a chymostatin-sensitive protease activity in the culture medium of S. pombe, which digests mouse alpha-amylase secreted into the culture medium. The addition of 5 micrograms/ml chymostatin was shown to protect mouse alpha-amylases from this degradation. PMID- 8511969 TI - Cystathionine gamma-lyase of Saccharomyces cerevisiae: structural gene and cystathionine gamma-synthase activity. AB - Purification of Saccharomyces cerevisiae cystathionine gamma-lyase (gamma-CTLase) was hampered by the presence of a protein migrating very close to it in various types of column chromatography. The enzyme and the contaminant were nevertheless separated by polyacrylamide gel electrophoresis. N-terminal amino acid sequence analysis indicated that they are coded for by CYS3 (CYI1) and MET17 (MET25), respectively, leading to the conclusion that CYS3 is the structural gene for gamma-CTLase and that the contaminant is O-acetylserine/O-acetylhomoserine sulfhydrylase (OAS/OAH SHLase). Based on these findings, we purified gamma-CTLase by the following strategy: (1) extraction of OAS/OAH SHLase from a CYS3-disrupted strain; (2) preparation of antiserum against it; (3) identification of a strain devoid of the OAS/OAH SHLase protein using this antiserum; and (4) extraction of gamma-CTLase from this strain. Purified gamma-CTLase had cystathionine gamma synthase (gamma-CTSase) activity if O-succinylhomoserine, but not O acetylhomoserine, was used as substrate. From this notion we discuss the evolutional relationship between S. cerevisiae gamma-CTLase and Escherichia coli gamma-CTSase. PMID- 8511970 TI - Sequence of the open reading frame of the FLO1 gene from Saccharomyces cerevisiae. AB - The cloned part of the flocculation gene FLO1 of Saccharomyces cerevisiae (Teunissen, A.W.R.H., van den Berg, J.A. and Steensma, H.Y. (1993). Physical localization of the flocculation gene FLO1 on chromosome I of Saccharomyces cerevisiae, Yeast, in press) has been sequenced. The sequence contains a large open reading frame of 2685 bp. The amino acid sequence of the putative protein reveals a serine- and threonine-rich C-terminus (46%), the presence of repeated sequences and a possible secretion signal at the N-terminus. Although the sequence is not complete (we assume the missing fragment consists of repeat units), these data strongly suggest that the protein is located in the cell wall, and thus may be directly involved in the flocculation process. PMID- 8511971 TI - A yeast gene encoding a putative RNA helicase of the "DEAD"-box family. AB - An unknown open reading frame from Saccharomyces cerevisiae was identified and sequenced. The predicted amino acid sequence shows high homology to the DEAD-box family of proteins. Gene disruption revealed that the gene is not essential for yeast but necessary for normal cell growth. PMID- 8511972 TI - Current awareness on yeast. PMID- 8511973 TI - Isolation of bovine intramuscular connective tissue. AB - This report presents a simple and rapid method for separating intramuscular connective tissue (IMCT) from bovine muscles. After lyophilization, muscle samples are blended and fibrous connective tissue is isolated from pulverized muscle protein by sieving. This method requires little expense in time and equipment, is easy to handle and therefore, is well suited to large sample output. The isolation of IMCT is necessary for further studies on intramuscular collagen. Recoveries and collagen enrichment of this method have been tested using several bovine muscles varying in collagen content. PMID- 8511975 TI - [Trigonelline in coffee. I. Comparison of thin layer chromatography with high performance liquid chromatography. Simultaneous determination of caffeine]. AB - Determination of trigonelline in several green and roasted coffees by thin-layer (TLC) and high-performance liquid chromatography (HPLC) were compared. Using TLC, two methods of detection were also compared. In addition, caffeine could be determined using HPLC. The determinations were each made with several variations of extraction and clean-up. Recoveries, variation coefficients and detection limits are listed. The most suitable method was HPLC in connection with hot water extraction. Only water is required as the mobile phase. The values for precision are in most cases better than (trigonelline) or similar to (caffeine) those reported in the literature. The determination of trigonelline by TLC, followed by extraction and photometry, is possible with a similar precision, but the simultaneous determination of caffeine was not tested. PMID- 8511974 TI - Carotenoid scavenging of radicals. Effect of carotenoid structure and oxygen partial pressure on antioxidative activity. AB - Carotenoid scavenging of free radicals has been investigated in peroxidizing methyl esters of unsaturated fatty acids using (i) metmyoglobin as a water-based free-radical initiator in a heterogeneous lipid/water system, and (ii) azo-bis isobutyronitrile as a free-radical initiator in a homogeneous chloroform solution. For the heterogeneous system, using a combination of electrochemical oxygen depletion measurements, spectrophotometric determination of lipid hydroperoxides and carotenoid degradation, it was demonstrated that each of the four carotenoids astaxanthin, beta-carotene, canthaxanthin, and zeaxanthin protects the methyl esters against oxidation. The antioxidative effect increases with increasing carotenoid concentration, increases with decreasing oxygen partial pressure (0.010 < pO2 < 0.50 atm), and shows little dependence on the structure of the carotenoid. For a homogeneous solution, the effect of the structure of the carotenoid was further investigated, and it was shown that the stability of the four carotenoids in the oxidizing system are different, with the order of decreasing stability being: astaxanthin > canthaxanthin > beta-carotene > zeaxanthin. Each of the four carotenoids can suppress lipid oxidation and the degree of suppression of peroxidation of methyl linoleate corresponds to the difference in stability. PMID- 8511976 TI - Polychlorinated biphenyl residues in food and human milk: determination of co planar and mono-ortho substituted congeners. AB - An analytical method is described for determining the residues of coplanar as well as mono-ortho substituted PCB congeners both exhibiting toxicological relevance, in foods of animal origin and in human milk. The unsophisticated procedure, convenient for routine analyses, includes the extraction of lipids, clean-up steps using liquid/liquid partition and column chromatography, fractionation of the congeners using HPLC on a special carbon column with an optimal gradient elution, and capillary column gas chromatography with electron capture or mass spectrometric detection. As preliminary results indicate, the low chlorinated PCB technical products contribute more to the actual contamination of environment and foods than has been estimated so far. Obviously the co-planar congeners are accumulated during the food chain in a portion different from that found for the other congeners. PMID- 8511978 TI - Effects of cadmium and mercury on growth and differentiation of Trichoderma viride. AB - Trichoderma viride showed distinct morphological changes and depressed growth rate in the presence of 1-10 mmol/l Cd2+. Several morphological mutants were isolated. In the presence of 1-5 mmol/l Hg2+ the growth of fungus was more inhibited but no mutants were obtained. PMID- 8511977 TI - Production of B-group vitamins by Azospirillum spp. grown in media of different pH at different temperatures. AB - Studies were carried out on B-group vitamin (thiamine, biotin, nicotinic acid, riboflavin, pantothenic acid) production by 3 strains of Azospirillum (one derived from coniferous ectomycorrhizae and two--from sporocarps of ectomycorrhizal fungi) grown in media of different pH (5.5, 6.5, 7.5) at different temperatures (10 degrees C, 20 degrees C, 26 degrees C). Riboflavin was produced in largest amounts by all the strains studied; biotin was not detected in culture filtrates at all. Qualitative-quantitative composition of vitamins in post culture liquids of azospirilla depended on the temperature of growth, pH of the medium and on the strain studied. Thiamine was synthesized in largest quantities at pH 5.5 by all strains of Azospirillum--independently of the temperature of growth. In media of higher pH this vitamin was detected in considerably smaller amounts or was not detected at all. The smallest quantities- and the smallest numbers of vitamins produced were observed at temperature 10 degrees C and pH 5.5. PMID- 8511979 TI - Ultrasound assessment of bone. PMID- 8511980 TI - Integrin expression in human bone. AB - Integrins are a family of heterodimeric transmembrane glycoproteins that are known to mediate cell-cell and cell-matrix interactions. Members of the VLA (very late activation) family, which consists of beta 1 integrin in association with the VLA alpha chains (alpha 1-6), mediate adhesion of a wide range of cells to matrix proteins, such as fibronectin, collagen, and laminin, and may therefore be important for cell-matrix interactions in bone. Integrin expression in human bone was studied immunohistochemically using cryostat sections of fracture callus, tumor-associated reactive bone, and neonatal costochondral junctions, with a panel of well-characterized antibodies against beta 1-4 integrins, alpha 1-6 and alpha V integrins, and the alpha V beta 3 dimer (the classic vitronectin receptor). All cell types present in bone expressed beta 1 and alpha 5 integrins; a subpopulation of osteoblastic cells expressed alpha 4. The alpha V was uniformly expressed by osteoblasts but was heterogeneously expressed by osteocytes. Osteoclasts also expressed alpha 2, alpha V, and alpha V beta 3. These results demonstrate differential expression of a restricted range of integrins in bone. This supports the possibility that integrins may mediate the differing interactions of cells of the osteoblast and osteoclast lineages with the matrix of bone. PMID- 8511981 TI - Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro. AB - We studied the effect of menatetrenone, a vitamin K2 homolog, on bone resorption stimulated by interleukin-1 alpha (IL-1 alpha), prostaglandin E2 (PGE2), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone resorbing activity was assessed by measurement of calcium and hydroxyproline in the media and calvariae. IL-1 alpha (0.1-100 U/ml), 1,25-(OH)2D3 (10(-10)-10(-7) M), PGE2 (10(-9)-10(-6) M), and PTH (3 x 10(-8)-3 x 10(-7) M) dose dependently increased the levels of calcium and hydroxyproline in the medium. Indomethacin (10(-6) M) completely inhibited bone resorption induced by IL-1 alpha and partially inhibited bone resorption induced by 1,25-(OH)2D3. However, indomethacin did not affect the action of PGE2 or PTH. Menatetrenone (3 x 10(-6) 3 x 10(-5) M) inhibited the bone resorption induced by IL-1 alpha (2 U/ml), PGE2 (10(-7) M), PTH (3 x 10(-7) M), and 1,25-(OH)2D3 (3 x 10(-10) M) in a dose dependent manner. Menatetrenone also inhibited the PGE2 production stimulated by IL-1 alpha. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechanisms; one possibly is an inhibitory effect on prostaglandin production. PMID- 8511982 TI - Secretion of osteocalcin and its propeptide from human osteoblastic cells: dissociation of the secretory patterns of osteocalcin and its propeptide. AB - Specific immunoassay systems for intact human osteocalcin (I-OC) and its 26 residue propeptide have been newly developed to assess their usefulness as biochemical markers of bone metabolism. Using human cultured osteoblastic periosteal cells, we monitored 24 h secretion of these molecules from the osteoblastic cells and also examined the deposition of Ca, P, and I-OC on the extracellular matrix. At day 5, both I-OC and its propeptide were secreted by osteoblastic cells in a concentration-dependent manner by treatment with 1,25 (OH)2D3. This propeptide was not detected in the serum of adult subjects but was detected in the serum of normal children, which confirmed this in vitro result of propeptide secretion. The secretion of I-OC into medium transiently decreased at day 11, when the rapid accumulation of I-OC, Ca, and P, namely mineralization, was observed on the extracellular matrix of osteoblastic cells, although secretion of the propeptide constantly increased throughout the culture period. Therefore, the ratio of the amount of propeptide to I-OC in the supernatant markedly increased when mineralization started. These data demonstrate the superior specificity of propeptide as a marker of osteoblastic function in vitro compared with I-OC and that monitoring the changes in propeptide to I-OC ratios in the culture supernatant may be useful for predicting the timing of mineralization on the extracellular matrix of osteoblastic cells. PMID- 8511983 TI - Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. AB - We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988-1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dualphoton absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9-19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8-6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948-1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause. PMID- 8511984 TI - Bone mineral density and mass in a cross-sectional study of white and Asian women. AB - The literature suggests that Asians have lower bone mineral density and mass than whites. It has been proposed that these differences may be due to differences in height, weight, and factors other than ethnicity, but no study has made the appropriate direct comparisons. We compared total-body bone mineral density and mass between Asian and white women while controlling for factors known to be associated with bone mineral density and mass. Measurements were made in 129 Asian (primarily of Chinese ancestry) and 274 white women. A subgroup was formed of women who did not have a history of alcoholism, premenopausal amenorrhea, kidney disease, estrogen use, birth control pill use, thyroid disease, steroid use, hysterectomy, or smoking. In both the main group and the subgroups, bone mineral mass was significantly lower in Asian than in white women, but after analysis of covariance with body weight, height, and age (or years since menopause) as covariates, the differences between ethnic groups disappeared, except in the large group of premenopausal women, in whom average bone mineral density in Asians actually exceeded (p < 0.04) that in whites. The data set was also searched for Asian-white pairs who matched on 17 characteristics related to bone mineral density and mass. In the resulting 16 matched pairs, bone mineral density and mass were not different between ethnic groups. Although Asian women have lower bone mineral mass than white women, when weight, height, and other factors are controlled, bone mineral density and mass do not differ between Asian and white women. PMID- 8511985 TI - Interleukin-1 receptor antagonist inhibits the hypercalcemia mediated by interleukin-1. AB - Recently, the effects of interleukin-1 (IL-1) on bone resorption in organ culture have been shown to be inhibited by an interleukin-1 receptor antagonist (IL-1RA), a novel monocyte cytokine in the IL-1 family. IL-1RA, which binds to IL-1 receptors and inhibits many of the effects of IL-1 alpha and beta, has been purified, cloned, and expressed. We used IL-1RA to investigate its effects on calcium homeostasis in vivo. After confirming that IL-1RA completely inhibited the effects of IL-1 on bone resorption in organ cultures, we tested the effects of IL-1RA on hypercalcemia mediated by IL-1 in normal mice and found that prolonged hypercalcemia provoked by IL-1 was completely inhibited by IL-1RA. The initial transient decrease in blood ionized calcium observed following an injection of IL-1 was also abrogated. IL-1RA had no effect alone on blood ionized calcium or on hypercalcemia mediated by parathyroid hormone (PTH) or PTH-related protein (PTHrP). These data suggest that antagonists to the IL-1 receptor may provide a useful therapeutic approach to osteoclastic bone resorption and hypercalcemia that is IL-1 dependent. PMID- 8511986 TI - Ontogenesis of ultrastructural features during osteogenic differentiation in diffusion chamber cultures of marrow cells. AB - Three stages of osteogenic differentiation can be identified in in vivo diffusion chamber cultures (DCC) of unselected marrow cells, namely, proliferation, differentiation, and maturation (mineralization). These stages were characterized correlatively by in situ differential cell counts, alkaline phosphatase activity, and mineral accumulation. In the present study, the ultrastructure of marrow cell DCC was examined after incubation for 3-21 days. Features characteristic of osteoblastic and chondroblastic differentiation were first noted in 12 day DCC. Sites of osteoblastic differentiation showed cell-cell contacts associated with an increased cell density. The osteoblastic cells had long processes and were embedded in matrix with prominent fiber bundles reminiscent of collagen type I. The chondroblastic cells appeared solitary in areas of lesser cell density. By contrast to the long osteoblastic cell processes, they had short plasmalemmal projections and the matrix surrounding them contained single, thin, short fibers reminiscent of collagen type II, as well as proteoglycan granules. Both cell types showed prominent cytoskeletal elements, rough endoplasmic reticulum, and Golgi. One finding, previously unnoted in differentiating osteogenic cells, was mitochondria with condensed cristae that represent an increased rate of energy metabolism. These mitochondria were particularly abundant in the differentiation stage and declined as the cultures matured. These findings, together with previous reports in the epiphyseal growth plate, suggest that mineralization is associated with an optimal level of energy metabolism rather than extreme hypo- or hyperoxia. The set of ultrastructural parameters defined here in the marrow cell DCC may serve as useful markers for cells undergoing osteogenic differentiation. PMID- 8511987 TI - Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. AB - Osteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow-up period. Therefore cross-sectional long-term followup studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross-sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple-regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan-Russell general outcome categories) deviated by -2.18 and -1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (-0.26 versus -0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems to proceed more slowly. PMID- 8511988 TI - An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. AB - Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15-25 per group) were sham operated or ovariectomized (OVX) and treated with 17 beta-estradiol (E2, 10 micrograms/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30-36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511989 TI - Production of leukemia inhibitory factor mRNA and protein by malignant and immortalized bone cells. AB - Leukemia inhibitory factor (LIF) is a recently characterized glycoprotein with complex biologic activities on bone cells. We tested various rodent and human immortalized and malignant bone cell lines and primary osteoblast-enriched cell cultures from fetal rat calvarial digests for expression of LIF mRNA and LIF protein. Both human and rodent immortalized and malignant cells expressed a single 4.4 kb mRNA transcript that hybridized to a human LIF cDNA probe in Northern blots. LIF mRNA was undetectable in unstimulated rodent osteoblast-like cells lines MC3T3-E1 and Py1a. However, treatment with LPS (10 micrograms/ml), TGF-beta (1 ng/ml), TNF-alpha (100 ng/ml) or inhibitors of protein synthesis (cycloheximide, emetine, puromycin, and anisomycin) induced the expression of LIF message in these cells. In contrast, primary osteoblast-enriched cells did not express LIF mRNA in Northern blot assays either constitutively or after treatment with TNF-alpha or cycloheximide. The human osteosarcoma cells lines U-2 OS and Saos-2 constitutively expressed LIF mRNA and did not respond to LPS treatment. However, phorbol myristate acetate (PMA), an activator of protein kinase C, was a potent stimulator of LIF message in Saos-2 but not U-2 OS cells. The effects of PMA (0.5 ng/ml) on LIF mRNA in Saos-2 cells were detectable at 1 h and maximal at 6 h. TNF-alpha (100 ng/ml) and inhibitors of protein synthesis also increased LIF mRNA in both Saos-2 and U-2 OS cells. LIF protein was also detected constitutively in the conditioned medium from both Saos and U-2 OS cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8511990 TI - Prostaglandin E2 administered by subcutaneous pellets causes local inflammation and systemic bone loss: a model for inflammation-induced bone disease. AB - The effects of prostaglandin E2 (PGE2) given in controlled-release pellets or by daily sc injection for 21 days on mineral homeostasis and bone histomorphometry were compared in 7-week-old female rats. Sham operation and ovariectomy were performed at the beginning of the studies. In experiment 1, 7.5 mg PGE2 or drug free, controlled-release pellets were implanted sc at the back of the neck on day 7. In experiment 2, 3 mg/kg body weight of PGE2 or vehicle was injected sc daily beginning on day 7. The animals were sacrificed on day 28 of the two experiments, and the tibiae were removed for histomorphometric analysis of the diaphysis and metaphysis. When administered by pellets in experiment 1, PGE2 lowered serum 1,25 dihydroxyvitamin D and did not influence weight gain, serum calcium, phosphorus, or magnesium, cross-sectional or medullary areas, periosteal bone formation and apposition rates, endosteal bone formation and apposition rates, or endosteal tetracycline-labeled perimeter. PGE2 lowered cancellous bone area and cancellous bone perimeter in both the sham-operated and ovariectomized rats. In contrast, when administered by sc injection in experiment 2, PGE2 reduced weight gain, increased serum magnesium, increased cortical area, and reduced medullary area without changing cross-sectional area, increased periosteal bone formation and apposition rates and endosteal bone and apposition rates, did not alter endosteal tetracycline-labeled perimeter, and increased cancellous bone area and cancellous bone perimeter in both sham-operated and ovariectomized animals. PGE2 produced local inflammation when given by pellets, and the serum concentration of 13,14 dihydro-15-ketoprostaglandin E2, the major metabolite of PGE2, increased when PGE2 was given by sc injection but not when administered by pellets. Thus, PGE2 given sc by controlled-release pellets (1) produces local inflammation and systemic bone loss without increasing PGE2 systemically and (2) provides a model for inflammation-induced loss of cancellous bone. The results also indicate that the pellet is not a valid means for the delivery of PGE2 to the general circulation. PMID- 8511991 TI - Immunoassay for urinary pyridinoline: the new marker of bone resorption. AB - Urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) are markers of bone resorption that are elevated above normal in subjects with metabolic bone disease. Total Pyd and Dpd, both free and peptide-bound forms, can be measured by HPLC after hydrolysis and cellulose chromatography. Since free Pyd is the major component of total Pyd in urine, we developed an immunoassay using free Pyd as an immunogen. This assay is much easier to perform than HPLC, requires no sample preparation, and correlates well with total Pyd measurement by HPLC (r = 0.97) and with urinary hydroxyproline (r = 0.90). The antiserum reacts most strongly with free Pyd and Dpd and minimally with glycosylated and large peptide-bound forms. The sensitivity of the Pyd immunoassay is less than 25 nM. The intraassay CV is 5-10%; the interassay CV is 10-15%. Analytic recovery studies indicated negligible sample interference. Furthermore, measurement of the Pyd in the same individuals over a 30 day time period exhibited minimal day-to-day variation. Thus, the Pyd immunoassay provides a rapid and easy method for evaluation of Pyd in urine. Pyd immunoassay may serve as a practical method of screening for metabolic bone disease and for monitoring therapeutic treatment. PMID- 8511992 TI - Immunoassay of pyridinoline crosslink excretion in normal adults and in Paget's disease. AB - A new immunoassay (ELISA) based on an antiserum that preferentially recognizes the free form of the pyridinoline (Pyr) crosslink was used to assess the urinary excretion of Pyr in a large normal sample of the population comprising 236 men and 193 women 30-90 years of age. Urinary Pyr increased significantly with age in both sexes. In women Pyr was higher than in men (57 +/- 21 versus 46 +/- 17 nmol/mmol creatinine, p < 0.001), and the menopause was reflected by a mean 37% increase, from an average 43 to 59 nmol/mm creatinine (p < 0.001). In 52 patients with active Paget's disease of bone, Pyr excretion was markedly increased (206 +/ 160 nmol/mmol creatinine, p < 0.001 versus controls) and decreased by 71% after 3 days of IV treatment with the bisphosphonate pamidronate. Free Pyr measured by the ELISA and the total urinary excretion measured by HPLC were highly correlated both in normals (n = 74, r = 0.83, p < 0.001) and in Pagetic patients (n = 20, r = 0.93, p < 0.001). The mean intra- and interassay coefficients of variation of the ELISA were below 9 and 15%, respectively. It is concluded that this new convenient immunoassay of Pyr should be valuable for the clinical investigation of patients with osteoporosis and other metabolic bone diseases. PMID- 8511993 TI - Effectiveness of phenol biodegradation as a function of the physicochemical parameters of the medium (II). AB - The effectiveness of phenol biodegradation as a function of the physicochemical parameters of the medium: temperature, pH, aeration, form of the inorganic source of nitrogen, presence of trivial substrates in the medium was studied. Using a two-factor dispersion analysis, the degree of influence of the various physicochemical parameters with regard to specificity of the biological factor was determined. Evaluation was made of the possibility to control the biodegrading process by means of physicochemical parameters of the medium. PMID- 8511994 TI - Determination of ichthiomycin concentration by biological test with Cyprinus carpio L. AB - We have found out that one-year-old carps are extremely sensitive to ichthiomycin in concentrations between 25-125 micrograms/dm3. This fact permitted the use of biological methods for determination of ichthiomycin concentrations in cultural medium of Streptomyces levoris 1107 or crude preparations of the antibiotic. PMID- 8511995 TI - Immunological and biochemical investigations of the infectious bovine rhinotracheitis. III. Alterations in pulmonary surfactant lipids. AB - The effect of experimental bovine herpes virus (BHV) type I rhinotracheitis on the surfactant system phospholipids in calves was examined. A stimulated exocytosis of pulmonary surfactant phospholipids in the acute phase of the disease was documented biochemically and ultrastructurally. The data presented were assumed as an evidence of the involvement of pulmonary surfactant in lung defense. PMID- 8511996 TI - Phosphatidylcholine-specific phospholipase C from Achromobacter xylosoxidans. AB - A new phosphatidylcholine-specific phospholipase C (EC 3.1.4.3.) has been isolated from the culture broth of Achromobacter xylosoxidans. Growth conditions were optimized for maximum production of the enzyme. A temperature-sensitive synthesis was established. Chromatography on CM Sephadex and polyacrylamide gel electrophoresis of the native enzyme revealed a number of isozymes. The water soluble substrate for phospholipase p-nitrophenylphosphorylcholine was not hydrolysed by the enzyme. PMID- 8511997 TI - Chemiluminescent activity of macrophages during phagocytosis of different bacterial forms. AB - Studies on the luminol-dependent chemiluminescent activity of rat peritoneal macrophages after in vitro interactions with E. coli WF+ L-form cells, their cytoplasmic membranes (CM) or parent bacterial cells were carried out. It was established that the phagocytosis of CM induce 20 time stronger light emission as compared to the L-form and 40 times compared to the parent bacterium cells respectively. Electron microscopical investigation of ultrathin sections of rat peritoneal macrophages after 24 h interaction in vitro with CM showed activation of the cell surfaces and vacuolisation of the cytoplasm. Inhibition of the phagolysosome fusion during phagocytosis of CM was observed. The mechanism of the immunostimulating activity of CM is discussed. PMID- 8511998 TI - Influence of the immunomodulators suramin, MER and clenbuterol on the haemopoiesis of mice with virus-induced Rauscher leukemia. PMID- 8511999 TI - Adjuvant activity of the Escherichia coli WF table L-form cytoplasmic membranes. AB - It was established that the stable E. coli WF+ L-form cytoplasmic membranes (CM) increase the antibody response in rabbit during experimental hyperimmunization with cells of Streptococcus pyogenes A49 and Proteus mirabilis D52. Using the skin-induration test and the reaction for aggregation of macrophages in presence of homologous antigens it was established that CM increase the cell-mediated immunity of guinea-pigs to protein antigens of the same bacterial strains. PMID- 8512000 TI - Radiometric study on the invasion capability of Streptococcus pyogenes A49 L forms in tissue cultures. AB - By a radiometric method using C14 labelled amino acid mixture it was established that the Streptococcus pyogenes A49 L-forms cells invade tissue cultures MK and F in a similar degree as parent bacterium cells. The L-form cells are not able to enter the HeLa and Pulmo tissue culture cells but the parent bacterium cells produce well expressed peak of isotope take-up at the 8th hour of the observation. PMID- 8512001 TI - Comparative study of different methods for extraction of Rubella haemagglutinin from infected cells BHK-21. AB - The results from a comparative study of some methods for extraction of Rubella haemagglutinin from infected BHK-21 cells are presented. The best haemagglutinin extraction was achieved after the cells were treated with Tween 80-ether. The combined application of alkaline extraction and Tween 80-ether treatment also gave good results. PMID- 8512002 TI - Dependence of the microbiological degradation of aryl-containing xenobiotics on their concentration. AB - The effect of concentration of the toxic substrates: phenol, oNph, mNph, pNph on their microbiological degradation was studied. The dependence was investigated at biocenotic and population levels. The aryl-catabolic properties of 55 biodegrading cultures were studied at an increasing gradient of phenol substrates. The degradation dynamics has been studied at different initial phenol concentrations on 3 bacterial and one yeast strains. PMID- 8512003 TI - Acute subdural haematoma in the conscious patient: outcome with initial non operative management. AB - We have retrospectively reviewed 23 conscious patients, in whom a CT scan diagnosis of acute subdural haematoma was made, and in whom craniotomy for evacuation was not initially performed. These highly selected patients represent 3% of 837 patients with acute subdural haematoma, presenting over a five year, eight month period to the Institute of Neurological Sciences, in Glasgow (1986 1991). Patients with any other associated intracranial abnormalities, such as cerebral contusions, as shown on CT, were excluded from this report. All patients were followed by serial CT scanning, and neurological assessments. Cerebral atrophy was present in over half of the sample. In 17 of our patients, the acute subdural haematoma resolved spontaneously, without evidence of damage to the underlying brain, as shown by CT or neurological findings. Six subsequently required burr hole drainage of a hypodense liquid subdural haematoma. In each of these patients, haematoma thickness was greater than 10 mm. Haematoma volume was significantly larger (53 +/- 6 ml versus 32 +/- 2 ml) in the group who came to operation. The mean delay between injury and operation in this group was 15 days. We conclude that certain conscious patients with small acute subdural haematomas, without mass effect on CT, may be safely managed conservatively. PMID- 8512004 TI - Pure subdural haematomas of arteriolar origin. AB - Fifteen consecutive cases of subdural haematomas (SDHs) of arteriolar origin operated on during the last twenty years in the Neurosurgical Clinic of the University of Genoa are reported. These SDHs are rare and form as a result of a rupture of a cortical arteriolar branch typically on the vicinity of the Sylvian fissure. They are always in a pure form and never associated with parenchymal lesions. Their aetiology is spontaneous, as in the 40% of our series, or more frequently related to minor traumas. These SDHs are often encountered in elderly patients generally presenting with severe clinical conditions (in the 60% of our patients GCS on admission was < 8). Prompt surgical treatment is required in all cases before further worsening of their neurological condition, even if CT scanning does not reveal parenchymal lesions. The mortality rate is over 50% and mainly relates to the pre-operative GC score. Clinical features, neuroradiological aspects and treatment are discussed and literature reviewed. PMID- 8512006 TI - Beta-blockade in acute aneurysmal subarachnoid haemorrhage. AB - The effects of beta-blockade to prevent autonomic disorders after acute aneurysmal subarachnoid haemorrhage were prospectively investigated. 11 patients were treated with the beta-1-selective beta-blocker metoprolol (up to 200 mg/die intravenously). 14 patients received standard therapy as controls. Pulse rate, blood pressure and dosage of the additional antihypertensive medication as signs of sympathetic disturbance were registered. The main result was the normalizing of the pulse rate especially during the first two weeks in contrast to the control group. The patients in the beta-blocker group did not need further antihypertensive medication. This was mainly a result of the reduction in sympathetic activation. No severe side-effects were documented and the survival was better in the treated group. Thus, beta-blockade is able to prevent and reduce autonomic disorders, especially activation of the sympathetic tone, in subarachnoid haemorrhage. Metoprolol as a so called cardioselective beta-blocker seems to be one of the suitable agents and is considered superior to the non selective agents. PMID- 8512007 TI - Repeat angiography and magnetic resonance imaging (MRI) of dissecting aneurysms of the intracranial vertebral artery. Report of four cases. AB - We here present 4 cases with dissecting aneurysm (DA) of the intracranial vertebral artery, who were followed up by repeat cerebral angiography and MRI. The patients consisted of 2 males and 2 females, and the mean age was 43 years. Two cases were associated with polyarteritis nodosa (PN) and hypertension, respectively. Three of the cases developed subarachnoid haemorrhage (SAH), while the other one suffered from lateral medullary syndrome. In cerebral angiography, "pearl and string" signs were revealed in all cases, while a "double lumen" indicating a true diagnostic sign of DA was demonstrated in only one case. Repeat angiography showed that a bleb formation with a bulging of the aneurysmal sac was seen in 2 cases, and an irregularity of the wall in one case. On the other hand in one case, the ectatic part shrank, while the stenotic part was restored. In magnetic resonance imaging (MRI), a hyperintensity mass on T 1-weighted image (T 1-WI) adjacent to flow void suggesting either an intramural haematoma or a linear shape hyperintensity on T 1-WI were demonstrated in 3 cases. In the follow up MRI done in 2 cases, a serial change in the intensity from iso-intensity to hyperintensity on T 1-WI was observed in one case suggesting intramural haemorrhage, while an enlargement of the ectasic flow void was seen in the other case. Three of 4 cases were operated on by trapping of the aneurysms. One, who had systemic vascular diseases due to PN, and repeat angiography showed a regression of the aneurysm, was conservatively treated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512005 TI - Does a safe size-limit exist for unruptured intracranial aneurysms? AB - Of 1076 patients with intracranial ruptured aneurysms (RA) included in the Danish Aneurysm Study, 948 had the RA verified by angiography. Of these cases 908 RA had a maximum diameter less than 25 mm. 162 RA were < 5 mm, 474 and 272 were between 5-10 mm and 11-24 mm, respectively. The average diameter of the RA according to the day of angiography after the aneurysm rupture did not differ significantly within the first 10 days. In these circumstances, using this indirect method for estimation of aneurysm rupture according to the size, we also recommend that unruptured aneurysms with a size 10 mm or less should be seriously considered for operation. PMID- 8512008 TI - Blood flow velocity in the middle cerebral artery and carotid artery stump pressure during carotid endarterectomy. AB - Twenty-one patients undergoing carotid endarterectomy were investigated by simultaneous intra-operative measurements of carotid stump pressure (CSP) and transcranial Doppler (TCD) flow velocity in the middle cerebral artery. The relationship between the two methods was evaluated as well as the potential benefits of the intraoperative transcranial Doppler monitoring technique. Clamping of the carotid artery resulted in a significant decrease in TCD flow velocity in the ipsilateral middle cerebral artery as well as in CSP. There was no correlation between relative change in CSP and the simultaneously obtained relative change in TCD flow velocity during carotid clamping (r = 0.31, p = 0.26). The insertion of an intra-operative shunt was followed by an increase in flow velocity compared to the clamping value. One patient with clear TCD signs of a re-occlusion (a sudden decrease in flow velocity) during closure of the wound, demonstrated a thrombosis at re-exploration. TCD gives information of the collateral cerebral circulation during carotid clamping and is an alternative monitoring technique during carotid endarterectomy. The method is useful intraoperatively for detecting embolic events as well as thrombosis during wound closure. Further studies are necessary to clarify the critical change in flow velocity during clamping when the use of a peroperative shunt is indicated. PMID- 8512009 TI - Transcutaneous pressure adjustable valve for the treatment of hydrocephalus and arachnoid cysts in adults. Experiences with 75 cases. AB - The authors report a series of 75 adults treated over the last four years for hydrocephalus (69 cases) or arachnoid cysts (6 cases) by using a transcutaneous pressure adjustable valve (Sophy SU 8), the mechanism of which is recalled. The shunt was ventriculo-atrial 46 times, ventriculo-peritoneal 23 times and cysto peritoneal 6 times. The opening pressure of the valve was initially adjusted 56 times to the medium, 9 times to the high, and 10 times to the low position, according to each particular patient's needs. Following the evolution of the neurological status and/or the CT findings, the opening pressure was secondarily modified in 27 patients (i.e., in 36%), and in some of them several times. It was raised 16 times: 10 times because of subdural hygroma(s) (complicated by a subdural haematoma which required surgical removal, in one case), and 6 times because of clinical symptoms of intracranial hypotension associated with hyperdrainage signs on CT. It was diminished 20 times because of the absence of clinical improvement and persistence of dilated ventricles on CT. In these 27 patients the Sophy SU 8 valve allowed modification of its opening pressure according to the clinical and CT evolution, without need for re-operation. It is concluded that the patients who can benefit most from this valve system are patients with normal pressure hydrocephalus or with arachnoid cysts. PMID- 8512010 TI - Linear accelerator and Greitz-Bergstrom's head fixation system in radiosurgery of single cerebral metastases. A report of 86 cases. AB - Between 1984 and 1991 86 patients with single cerebral metastases underwent linear accelerator radiosurgery using the atraumatic and reproducible Greitz Bergstrom head-fixation device. Routine one-month follow-up documented disappearance of the tumour in 16 patients, with resolution of the oedema and ventricular shift. Shrinkage of the metastasis occurred in 51 patients. In 9 patients the tumour remained stable, in 7 there was progression of tumour size. Among the patients showing shrinkage of the tumour or unchanged tumour volume, repeated radiosurgery resulted in disappearance of the metastasis in 5 and further shrinkage in 28. In 14 patients routine stereotactic CT follow-up study led to the detection of a new metastasis, again treated with excellent results. Local recurrence occurred in 2 patients and radiation necrosis in the target area in 5 patients. Radiosurgery thus proves to be an appropriate alternative to surgery. The versatility of our non-invasive and painless method permits CT staging (which we consider essential) without hospitalization of the patient. PMID- 8512011 TI - Persistent activation of thrombocytes in neurosurgical patients operated for primary brain tumours. AB - A prospective study was designed to investigate whether platelet hyperactivity exists following neurosurgical removal of primary brain tumours. The level of beta-thromboglobulin (beta TG), a protein released by platelets during the activation process, was measured in the plasma of 13 consecutive patients prior to surgery (T 1) and on the first (T 2) and seventh (T 3) post-operative days. A significant and sustained increase in beta TG levels from a baseline of 20.7 +/- 1.7 ng/ml (mean +/- sem) at T 1 to 37.0 +/- 5.2 ng/ml (p < 0.005) at T 2 and 35.9 +/- 3.7 at T 3 (p < 0.005) occurred. When patients were grouped according to tumour malignancy, significantly higher beta TG levels were found in the malignant group at T 2 (51.8 +/- 6.3 ng/ml) when compared to the benign group (30.6 +/- 6.0 ng/ml) (p = 0.025). Postoperative T 3 levels were linearly correlated to T 1 levels (r = 0.58, p = 0.04). This significant and sustained platelet activation that occurs following brain surgery may be part of the biochemical sequel leading to a hypercoagulable state and thrombo-embolic phenomena (TEP) in these patients. PMID- 8512012 TI - Serum adenosine deaminase activity in brain tumours. AB - Adenosine deaminase (ADA) activity in serum was estimated in 86 patients with intracranial tumours and 40 healthy volunteers. Although high ADA concentrations in biological fluids and tumour tissues were observed in several neoplastic conditions, there was no significant difference in the ADA in sera of brain tumour patients when compared to the control values. Therefore, cell-mediated immunity probably does not play a significant role in brain tumours. PMID- 8512013 TI - Pituitary granuloma and chronic inflammation of hypophysis: clinical and immunohistochemical studies. AB - We describe five patients with chronic inflammation of the hypophysis including three pituitary granulomas of unknown aetiology. In contrast to the previously reported cases, the involvement of neurohypophysis or hypothalamus was a distinct clinical feature in these patients. Impairment of anterior pituitary function was less prominent, while polyuria and polydipsia occurred in all cases. Enlargement of the sella turcica was absent in three and slight in two cases. CT scan and MR images demonstrated a contrast-enhanced sellar mass in all patients; abnormally thickened pituitary stalk and infundibulum with contrast-enhancement was observed in four. The fibrous tissues were removed by the transsphenoidal approach in four patients, and by the subfrontal approach in one case. In all patients, the endocrinological dysfunction was prolonged. No increase in the size of the remaining pituitary mass was demonstrated on repeated MR images in any of the patients. On histological examination, granulomatous formation was present in three samples, and multinucleated Langhans' giant cells were seen in one. The epithelioid cells and multinucleated giant cells constituting the granulomas were positive for anti-macrophage antibody. No firm laboratory or histological evidence was obtained supporting the presence of systemic disease leading to granulomas. In the other two cases, the pituitary lesions were composed of chronic inflammation tissue, and serum antipituitary antibodies were present in a patient with concurrent Hashimoto's thyroiditis. Our experiences with chronic inflammation of the hypophysis indicate that these patients are best managed by histological confirmation of the lesion followed by adequate hormonal replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512014 TI - CO2 cerebrovascular reactivity as a function of perfusion pressure--a modelling study. AB - A mathematical model is described that demonstrated the properties of cerebral vascular resistance and compliance expressed as a function of cerebral perfusion pressure (CPP) and arterial CO2 partial pressure (PaCO2). The hypercapnic induced shift of the lower limit of autoregulation to a higher range of CPP, as shown by this model, is a useful characteristic that facilitates the differentiation between normal and impaired autoregulation described previously in experimental studies. Dynamic properties of cerebrovascular circulation derived from the relationship between pulse wave of CBF waveform and CPP have been analysed at different levels of PaCO2-phenomenon, being often described as dependence of blood flow velocity pulsatility index on the autoregulatory reserve. The model was also used to interpret interhemispheric asymmetry of CBF reactivity to changes in arterial concentration of CO2 in patients with carotid artery stenosis. PMID- 8512015 TI - Cerebral blood flow and glucose metabolism in the squirrel monkey during the late phase of cerebral vasospasm. AB - A double-isotope autoradiography technique was used to evaluate cerebral blood flow (CBF) and cerebral glucose metabolism (CMRglu) during the late phase of vasospasm in a squirrel monkey subarachnoid haemorrhage (SAH) model. Cisternal blood injections induced both global and focal changes in CBF and CMRglu six days following SAH, the timepoint of maximal late spasm in this model. There was a global decrease in CBF of about 30% accompanied by an increase in deoxyglucose uptake of about 50%. Four of seven animals also had foci with flow decreased to 40% of control and deoxyglucose uptake increased to 300% of control. There was an altered but still present interdependence between flow and metabolism post SAH. PMID- 8512016 TI - In vivo effect of visible light on feline cortical microcirculation. AB - The present study was designed to test the hypothesis that prolonged illumination of the cerebral cortex, for instance during neurosurgical interventions, may affect the pial microcirculation. Experiments were performed with the closed window technique in cats. The cortical surface below the window was exposed to visible, cold light of 61,000 lumens/m2 (lux) over a period of 1 to 5 hours. Pial arterioles reacted with a slight initial dilatation to 106.8 +/- 2.6% of their resting diameter after switching to the high intensity light. Measurements of the cortical surface temperature showed an average temperature increase of 1.5 +/- 0.34 degrees C within the first 10 minutes of illumination. For assessment of pial vascular function, the responses to topical application of acetylcholine (ACh) were tested before and during the illumination period. The effect of sustained illumination on the cortical microcirculation consisted of abolition of the endothelium dependent relaxation due to ACh, and of intravascular thrombus formation, the latter, however, only in the presence of topically applied ACh. The suspected mechanism responsible for these functional alterations is light induced generation of free oxygen radicals which are known to inactivate or destroy the endothelium-derived relaxing factor (EDRF). Further studies are recommended to elucidate the practical and clinical relevance of these findings to neurosurgical procedures. PMID- 8512017 TI - Oblique transcorporeal approach to anteriorly located lesions in the cervical spinal canal. AB - The technique of obliquely drilling out the postero-lateral part of the cervical vertebral bodies is described. It uses the antero-lateral (retro carotico jugular) approach to control and displace the vertebral artery postero-laterally and to expose the lateral aspect of the vertebral bodies. It provides, through a wide field and with minimal retraction of the carotid artery and the internal jugular vein, an extensive view of the anterior aspect of the spinal cord. It has already been used to treat 15 anterior lesions compressing the spinal cord including neurinomas and osteophytes. PMID- 8512018 TI - Expression and release of interleukin-1 by human glioblastoma cells in vitro and in vivo. AB - The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1 alpha and IL-1 beta transcripts was analyzed in 4 cell lines. IL-1 alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1 beta mRNA could not be detected in any of the cell lines. IL-1 alpha transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell lines and IL-1 beta mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radio-immuno-assay for either IL-1 alpha or IL-1 beta. In agreement with the results on RNA, one of 4 cell lines was found to constitutively produce IL-1 alpha but not IL-1 beta. After treatment with PMA and LPS, IL-1 alpha was detected in the culture fluid from two other lines and IL-1 beta in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay. Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cells in vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1 alpha monoclonal antibody while none of them was stained with an anti IL-1 beta antibody. PMID- 8512019 TI - Diffuse leptomeningeal melanomatosis of the spinal cord: a case report. AB - A rare case of diffuse leptomeningeal melanosis presenting with symptoms of spinal cord compression due to the presence of anterolateral arachnoid cyst and treated with Spetzler's drainage system is reported. The diagnosis of diffuse melanosis of the leptomeninges is rarely possible during life. In the present case MRI was of great help in the definition of the limits of the pathological process and the presence of the anterior compressing cyst. After laminectomy and a biopsy of the pathological tissue which achieved the histological diagnosis, an external drainage was inserted to reduce the cyst extension and to exclude the presence of melanocytes in the cystic fluid before a peritoneal shunt was placed. At 8th month of follow-up the patient is doing well with a dramatic reduction of symptoms and a significant reduction of spinal cord compression. The diagnostic role of MRI and the relationship between leptomeningeal melanosis and arachnoid cyst are discussed. PMID- 8512020 TI - Even the smallest remnant of an AVM constitutes a risk of further bleeding. Case report. AB - A case with an ill-defined arteriovenous malformation in the parieto-occipital region is presented. Open surgery was unsuccessful in removing the AVM totally, and treatment with gamma knife radiosurgery was then attempted. At 14 months after this treatment the AVM was believed to be obliterated. The patient had a new intracranial haemorrhage 59 months after radiosurgery. Renewed angiography showed an obvious AVM outside the previously irradiated area. Retrospective analysis of the angiogram at 14 months after radiosurgery revealed early filling of a draining vein as a sign of residual AVM at this time. Renewed radiosurgical treatment was performed. It is believed that an ill-defined margin, laminar flow, and effects of previous surgery might add to difficulties in a proper visualisation and delineation of an AVM. Further, a small remaining shunt may be overlooked if the angiogram is not carefully analysed or if the angiogram is of inferior quality. It should be stressed that partial or almost total obliteration of an AVM is no protection against rebleeding. PMID- 8512022 TI - [Comorbidity in personality disorders]. PMID- 8512023 TI - [Classifications of mental disorders: from Bertillon to ICD-10, the century of international collaboration]. AB - The first International Classification of Diseases (ICD) was approved during the Congress of the Statistical International Institute, in Chicago, in Paris, in 1893. It was based on a list of diseases prepared by Jacques Bertillon. Minor changes were introduced in this classification during decennial revisions made at international meetings and it remained in use until 1948, when the World Health Organization's Provisional Committee was charged with the task producing ICD-6. ICD-6 represented a major shift from the previous internal conceptualization, particularity in what concerns the Chapter V., dealing with mental disorders. From 1955 on Who produced with approximately a 10-year interval ICD-7, 8 and 9. Few modifications in relation to ICD-6 were introduced by these revisions, except for the introduction of a glossary of terms in the chapter on mental disorders. This glossary had a major impact towards the development of a common language in psychiatry. Based on epidemiological findings, and based also on an intensive and extensive international network of clinicians and investigators, ICD-10 was published in 1992. It represented a substantial improvement regarding the conceptualization of the classification of mental disorders, in relation to previous revisions of the ICD. Future tasks relating to ICD-10 include training of health personnel for its proper utilization, in addition to finalizing further ICD-10 versions, e.g. for research purposes and for primary health care use. PMID- 8512021 TI - Acute subdural haematoma in adults: an analysis of outcome in comatose patients. AB - The authors analysed a series of 200 adult patients admitted to the Department of Neurosurgery, Medical University of Lodz with a diagnosis of acute subdural haematoma (ASDH). 63% of them were surgically treated within the first 4 hours after head injury, the others were operated on 4 to 16 hours after trauma. All patients had GCS below 10 for the whole time period from trauma to surgery. Younger patients 18-30 year old had lower mortality-25%, while patients above 50 revealed 75% mortality. Analysis of operative timing and outcome, no benefit revealed when surgery was performed within first 4 hours. However, the patients operated on later than 4 hours after trauma had smaller midline shift and less pronounced brain contusion. It must be taken into account that some patients who could benefit from early surgery-those with quickly developing haematomas and intracranial hypertension-had no chance to arrive and died in peripheral hospitals. Despite our results we advocate an urgent evacuation of haematoma, as early as possible after trauma. Significant correlation was found between midline shift, cerebral contusion on CT scans and results of surgery. Patients with bigger midline shift or presence of focal cerebral contusion revealed higher mortality and worse outcome than patients with smaller shift and no cerebral contusion visible on CT pictures. PMID- 8512024 TI - [Bibliographic analysis of the concept "alcohol-related problems"]. AB - This survey, which is related to one of the research lines of our Unit, has a main objective to conduct a bibliographic analysis, in the medical literature of the "Alcohol Related Problems", (A.R.P.) concept. For this reviewed, by means of the MEDLINE data base, the last five years of the international scientific literature, selecting as key words: "Alcohol Related Problems", "Epidemiology", "Alcohol Drinking", "Social Problems". We detected 215 publications with abstracts, 174 presented data from epidemiological surveys and the remaining 31 were related to theoretical aspect. In 90 per cent of the revised articles alcohol was considered a risk factor and cause of illness; however, only 13 percent of them used the A.R.P. terminology. The majority of these studies were related to epidemiological surveys, mainly of a descriptive nature and with a cross-sectional or a retrospective design. We also identified, among other things, an increasing interest for the medical and social aspects of the A.R.P., this appears to be related to a more innovative view of this health problems. PMID- 8512025 TI - [The development of the index of probability of psychosocial adaptation of chronic kidney patients]. AB - Variables obtained from statistical techniques of multivarying analysis, related to psychosocial adaptation of chronic renal patients on treatment were applies in order to construct an index for the probability of the psychosocial adaptation of chronic renal patients (I.P.P.A.C.R.P.). The probability of 1% adaptation determines correctly to 97% of the cases with high sensibility and specificness thus is convenient to wait for the crossed validation of other investigators. PMID- 8512026 TI - [Health advantages with the use of oral contraception]. PMID- 8512027 TI - [Oral contraceptives and cardiovascular disease]. PMID- 8512028 TI - [Oral contraceptives in Latin America]. PMID- 8512029 TI - [Oral contraceptives and cancer]. PMID- 8512030 TI - [Metabolic effects of oral contraceptives]. PMID- 8512031 TI - [Oral contraceptives and women 35 years of age and older]. PMID- 8512032 TI - [General evaluation of oral contraceptives]. PMID- 8512033 TI - Lymphokine and cytokine production by Fc epsilon RI+ cells. PMID- 8512034 TI - B lymphopoiesis in the mouse. PMID- 8512035 TI - Compartmentalization of the peripheral immune system. AB - The periphery of the immune system--as opposed to the central lymphoid organs- contains inhomogeneously distributed B and T cells whose phenotype, repertoire, developmental origin, and function are highly divergent. Nonconventional lymphocytes bearing a phenotype that is rare in the blood, spleen, or lymph nodes of undiseased individuals are encountered at high frequency in different localizations, e.g., alpha/beta TCR+CD4-CD8- cells in the bone marrow and gut epithelium, particular invariant gamma/delta TCR+CD4-CD8 alpha+CD8 beta- and gamma/delta TCR+CD4-CD8 alpha-CD8 beta- T cells in various epithelia, or CD5+ B cells in the peritoneum. The antigen receptor repertoire is different in each localization. Thus, different gamma/delta TCR gene products dominant in each site, and the proportion of cells expressing transgenic and endogenous alpha/beta TCR and immunoglobulin gene products follows a gradient, with a maximum of endogenous gene expression in the peritoneum, intermediate values in other peripheral lymphoid organs (spleen, lymph nodes), and minimum values in thymus and bone marrow. Forbidden T cells that bear self-superantigen-reactive V beta gene products are physiologically detected among alpha/beta TCR+CD4-CD8- lymphocytes of the bone marrow, as well as in the gut. Violating previous ideas on self-tolerance preservation, self-peptide-specific gamma/delta T cells are present among intestinal intraepithelial lymphocytes, and CD5+ B cells produce low-affinity crossreactive autoantibodies in a physiological fashion. It appears that, in contrast to the bulk of T and B lymphocytes, certain gamma/delta and alpha/beta T cells found in the periphery, as well as most CD5+ B cells, do not depend on the thymus or bone marrow for their development, respectively, but arise from different, nonconventional lineages. In addition to divergent lineages that are targeted to different organs guided by a spatiotemporal sequence of tissue-specific homing receptors, local induction or selection processes may be important in the diversification of peripheral lymphocyte compartments. Selection may be exerted by local antigens, antigen-presenting cells whose function varies in each anatomical localization, cytokines, and cell-matrix interactions, thus leading to the expansion and maintenance of some clones, whereas others are diluted out or deleted. The spatial compartmentalization of lymphocytes in different microenvironments has major functional consequences and leads to a partial fragmentation of immunoregulatory circuits at the local level. Lymphocytes residing in certain antigen-exposed compartments are likely to combat tissue-specific pathogens or self-proteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8512036 TI - Immunological memory. PMID- 8512037 TI - Cell adhesion molecules as targets of autoantibodies in pemphigus and pemphigoid, bullous diseases due to defective epidermal cell adhesion. PMID- 8512038 TI - The leukemia inhibitory factor and its receptor. PMID- 8512039 TI - Role of CD4 and CD8 in T cell activation and differentiation. PMID- 8512040 TI - Contraceptive Choices for Women with Medical Problems. Symposium proceedings. Rancho Mirage, California, May 7-10, 1992. PMID- 8512041 TI - Impact of contraception on gynecologic cancers. AB - In considering the appropriate contraceptive method for a particular woman, the potential effect of that method on her risk of developing cancer of the breast, cervix, endometrium, or ovary is crucial. Among the most closely studied of the risk factors for gynecologic neoplasm has been the potential role of contraceptives, especially oral contraceptives, intrauterine devices, and injectable progestins. Physicians need to consider the potential impact of these agents on the disease process, therapy for the disease, future fertility, and the health of the fetus. Although much of the epidemiologic data is inconsistent and difficult to interpret, most studies find no association between oral contraceptive use and increased risk of breast cancer, except possibly in younger women (< 45 years of age) with prolonged use. Oral contraceptive use may also protect against benign breast disease. Data concerning oral contraceptive use and cervical neoplasm are confounded by several interacting variables, the most important of which is that oral contraceptive users tend to have more Papanicolaou smears than nonusers. Some studies have indicated an increased risk of two- to fourfold after 10 years of use. Oral contraceptive use provides clear protection against endometrial and ovarian cancer, an effect that persists for years after discontinuation. Less data have been collected regarding the relationship between intrauterine devices and injectable hormonal preparations and various types of cancer. No evidence suggests that the intrauterine device predisposes to the development of preneoplastic conditions of the cervix, nor to endometrial or ovarian cancer. A reliable form of contraception is indicated in women with cancer of any kind that may require chemotherapy or radiation, because these treatments can have adverse effects on the fetus, especially if given during the first trimester. PMID- 8512042 TI - Contraceptive choices for behaviorally disordered women. AB - Women with psychologic disturbances of depression, anxiety, or thought disorganization pose a special management problem when providing a safe and effective means of contraception. The difficulty is compounded by the fact that many mentally disturbed women also abuse drugs. Therefore, providing contraception to the many types of behaviorally disturbed women requires the full range of contraceptive options and protection from sexually transmitted diseases. When compliance can be assured, oral contraceptives are the preferred method. When compliance is questionable, progestin implants or injections may be tried. However, progestin-only preparations are associated with several side effects, including worsening of mood in depressive patients. PMID- 8512043 TI - Contraceptive choices in women with coagulation disorders. AB - When compared with older reports on the thromboembolic effects of high-dose oral contraceptives, new studies with low-dose oral contraceptives have a significantly reduced risk of thromboembolism. In the absence of risk factors such as smoking or inherited disorders predisposing to thrombosis, the modern low dose oral contraceptive (< 50 micrograms of estrogen) is a safe and effective choice for contraception in women without symptoms who have family histories of sporadic thromboembolism. An intrauterine device or some form of barrier method is recommended for women who have a personal history of venous thrombus disease. The low-dose oral contraceptive may be a good choice in women taking oral anticoagulants because of the risk of teratogenic effects of anticoagulants and the risks of intraperitoneal bleeding associated with ovulation. In addition, oral contraceptives help diminish the excessive menstrual bleeding often seen in these women. PMID- 8512044 TI - Contraception and dyslipidemia. AB - The risks of cardiovascular disease associated with dyslipidemia differ in women and men, being more strongly associated with triglyceride/high-density lipoprotein in middle-aged women than in men. Although the incidence of heart disease is lower in women because they live longer, over a lifetime, cardiovascular disease in women is equal to that in men, with the greatest incidence after age 65 years. Major coronary events are rare among reproductive age women who use oral contraceptives and are related to the concomitant effects of age, smoking, diabetes, hypertension, and obesity. Low estrogen-progestin dose oral contraceptives appear not to promote cardiovascular disease and can be used in women with controlled cholesterol elevations. Alternative contraceptive measures should be considered for patients with severe uncontrolled hypercholesterolemia or a lipid disorder that carries a high risk of coronary heart disease. In these conditions, thrombotic propensity associated with supraphysiologic doses of estrogen in oral contraceptives might accelerate coronary thrombosis should an arteriosclerotic plaque rupture. Treatment of hypercholesterolemia should follow the guidelines of the National Cholesterol Education Program and emphasize hygienic measures. Contraceptive selection in hyperlipidemic patients should reflect a balance between the risks--and their management--of developing cardiovascular disease versus the risks of pregnancy. PMID- 8512045 TI - Considerations for contraception in women with cardiovascular disorders. AB - Women with hypertension, angina pectoris, or mitral valve prolapse require special considerations when selecting an appropriate method of contraception. All three effective, reversible options (oral contraceptives, intrauterine devices, or progestin implants) carry some degree of added risk for these patient populations. However, pregnancy itself presents certain risks and, in the event of contraceptive failure, certain women with these disorders are at increased risk of developing serious cardiovascular sequelae that affect both mother and fetus. These negative effects can carry far into the neonatal period. This article describes the risk/benefit profiles of the currently available contraceptive options relative to their potential impact in these compromised women. PMID- 8512046 TI - Diabetes mellitus and fertility control: contraception management issues. AB - The need to prevent complications in the woman and fetus mandates that pregnancies in diabetic women always be planned and that safe and effective contraceptives be used at all times until it is determined that pregnancy is a safe and desired option. Pregnancy may aggravate complications of diabetes such as retinopathy and coronary artery disease. A pregnant diabetic woman is also more likely to experience such complications as hypertension, urinary tract infection, polyhydramnios, and cesarean section. Her fetus is at increased risk for congenital malformations, prematurity, stillbirth, neonatal morbidity, and diabetes later in life. Good diabetic control must be maintained before and throughout the pregnancy to minimize the risk of these and other complications. Until such time as good control is achieved and the woman desires pregnancy, a reliable method of contraception should be used. Most recent research supports the use of barrier methods, low-dose monophasic or triphasic oral contraceptives, or progestin-only methods, at least for the short-term. Under some circumstances the intrauterine device may be an appropriate option. Long-term data regarding the use of these methods is lacking. The decision regarding which method of contraception is used should be made by the woman in consultation with her physician. PMID- 8512047 TI - Contraceptive choices for women with endocrine complications. AB - Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion. PMID- 8512049 TI - Contraception and sexually transmitted diseases: interactions and opportunities. AB - Today "safe sex" means protection from both unintended pregnancy and sexually transmitted disease and human immunodeficiency virus. These parallel complications of sexual activity have serious biologic and clinical sequelae that should be considered at the time of contraceptive selection. In addition, there is ongoing debate regarding potential interactions between antibiotic intervention and contraceptive steroids. This article assesses the impact of hormonal contraception, spermicides, barrier methods, intrauterine devices, and douching on the pathogenesis of sexually transmitted disease and the human immunodeficiency virus infection. It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while also considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception. Counseling and care for both family planning and infectious disease protection must be provided to all sexually active individuals. PMID- 8512048 TI - Contraceptive methods for women with neurologic disorders. AB - Sex steroids in oral contraceptives exert several effects on the central nervous system and are therefore of concern when used by neurologically compromised women. In general, oral contraceptives do not aggravate epileptic seizures and are not contraindicated in cases of tension headache. Oral contraceptives can be used in cases of migraine without focal neurologic symptoms as long as headache symptoms do not worsen. Levels of sex steroids can be diminished through enzyme induction by antiepileptic drugs, giving rise to the possibility of contraceptive failure and exposure of the fetus to the teratogenic properties of antiseizure medications. Women with common migraine (without focal neurologic symptoms) who are taking oral contraceptives should be monitored for possible exacerbation of their symptoms. Women who do experience worsening of headache symptomatology when taking the pill should consider alternate means of contraception. PMID- 8512050 TI - Unwanted pregnancies: understanding contraceptive use and benefits in adolescents and older women. AB - The highest percentages of unintended pregnancies and the largest increases in births reported in the United States in recent years were in adolescents and in women more than 35 years of age. Increasing numbers of these women will require contraception to avoid unintended pregnancy. In adolescents the combined oral contraceptive agents protect fertility indirectly and exert favorable actions on menstrual dysfunction and certain hormone-related disorders such as acne and hirsutism. To avoid sexually transmitted disease, barrier protection should be used along with oral contraceptives until mutually monogamous, stable relationships are established. Healthy older women who are nonsmokers may also safely use currently available contraceptives. These agents have little impact on metabolic parameters linked to the development of cardiovascular disease. In addition to providing reliable contraception, oral contraceptives offer noncontraceptive benefits to older reproductive-age women, including control of abnormal bleeding and a reduction in the incidence of ovarian and endometrial cancers and other gynecologic pathology. Intrauterine devices and progestin implants are safe, effective, and underused in the United States. Progestin implants may have an additional role in patients for whom estrogen preparations are contraindicated. Counseling is very important before insertion because of the high rate of nuisance side effects. The contraception selection process must consider the efficacy and acceptability of the specific method to avoid the probability of unintended pregnancy and the risk of sexually transmitted diseases. PMID- 8512051 TI - Biomechanical analysis of masticatory system configuration in Neandertals and Inuits. AB - Considerable debate has surrounded the adaptive significance of Neandertal craniofacial morphology. Numerous unique morphological features of this form have been interpreted as indicating an adaptation to intense anterior tooth use. Conversely, it has been argued that certain features related to muscle position imply a reduced mechanical advantage for producing bite forces on the incisors and canines. In this study, hypotheses about morphological specializations for anterior tooth use have been derived from a biomechanical model of Greaves (1978). These hypotheses were tested by performing separate pairwise comparisons of Neandertals and early Homo sapiens, and Inuits and Native Americans from Utah. Inuits are known to have produced repeated and high magnitude forces on their anterior dentition and therefore serve as a good model for a hominid adapted to intensive anterior tooth use. Biomechanically relevant dimensions of the masticatory system were measured using a computer-driven video analysis system and compared between the two taxa in each comparison. The results of this study reveal a number of similarities between the morphological specializations exhibited by Neandertals and Inuits that can be related to intensified anterior tooth use. The hypothesis that Neandertals were poorly designed for producing masticatory forces is rejected. Specializations that differ between the two groups are interpreted as being the result of differential functional demands placed on the postcanine dentition in Neandertals and Inuits. It is suggested that many of the unique morphological features of the Neandertal face are a response to intensified use of the anterior dentition and the need to retain a sufficiently large postcanine occlusal area necessary for a relatively high attrition diet. PMID- 8512052 TI - Longitudinal study of cranial base shape changes in Macaca nemestrina. AB - The primate cranial base (CB) represents a complex irregular structure even when limited to two dimensions, making it difficult to describe quantitatively using the conventional metrical approach composed of angles and distances. Consequently, a curve-fitting procedure, elliptical Fourier functions (EFF), was utilized, which accurately defines the form of complex two-dimensional morphologies. A longitudinal Macaca nemestrina sample consisting of 14 females and 15 males was utilized. Lateral headfilms, 1 to 8 years, were available (275 headfilms). Because the x-rays were not always taken at precise one-year intervals, a number of headfilms were excluded, which reduced the sample to 181. The CB boundary outline was carefully traced onto acetate sheets and 54 points located. The observed points were digitized and used to compute size-standardized EFF's with 20 harmonics. From each EFF, a set of 150 expected distances to the CB boundary was generated using the centroid as an origin. Superimposition of the CB's on the centroid also provided a detailed picture of the relative shape changes with respect to that center. Statistically significant shape differences were found as a function of age and sexual dimorphism. These age changes consisted of a gradual anteroposterior lengthening with a concomitant narrowing in the superoinferior direction. Specifically, a lengthening of the dorsal clivus and an anterior migration of the hypophyseal fossa could also be discerned. Thus, Fourier descriptors provide a particularly powerful method for documenting, both visually and numerically, the shape changes of complex two dimensional morphologies. PMID- 8512053 TI - Postcranial robusticity in Homo. I: Temporal trends and mechanical interpretation. AB - Temporal trends in postcranial robusticity within the genus Homo are explored by comparing cross-sectional diaphyseal and articular properties of the femur, and to a more limited extent, the humerus, in samples of Recent and earlier Homo. Using both theoretical mechanical models and empirical observations within Recent humans, scaling relationships between structural properties and bone length are developed. The influence of body shape on these relationships is considered. These scaling factors are then used to standardize structural properties for comparisons with pre-Recent Homo (Homo sp. and H. erectus, archaic H. sapiens, and early modern H. sapiens). Results of the comparisons lead to the following conclusions: 1) There has been a consistent, exponentially increasing decline in diaphyseal robusticity within Homo that has continued from the early Pleistocene through living humans. Early modern H. sapiens are closer in shaft robusticity to archaic H. sapiens than they are to Recent humans. The increase in diaphyseal robusticity in earlier Homo is a result of both medullary contraction and periosteal expansion relative to Recent humans. 2) There has been no similar temporal decline in articular robusticity within Homo--relative femoral head size is similar in all groups and time periods. Thus, articular to shaft proportions are different in pre-Recent and Recent Homo. 3) These findings are most consistent with a mechanical explanation (declining mechanical loading of the postcranium), that acted primarily through developmental rather than genetic means. The environmental (behavioral) factors that brought about the decline in postcranial robusticity in Homo are ultimately linked to increases in brain size and cultural-technological advances, although changes in robusticity lag behind changes in cognitive capabilities. PMID- 8512054 TI - Genetic relationships of European populations reflect their ethnohistorical affinities. AB - From 420 records of ethnic locations and movements since 2000 B.C., we computed vectors describing the proportions which peoples of the various European language families contributed to the gene pools within 85 land-based 5 x 5-degree quadrats in Europe. Using these language family vectors, we computed ethnohistorical affinities as arc distances between all pairs of the 85 quadrats. These affinities are significantly correlated with genetic distances based on 26 genetic systems, even when geographic distances, a common causative factor, are held constant. Thus, the ethnohistorical distances explain a significant amount of the genetic variation observed in modern populations. Randomizations of the records by chronology result in loss of significance for the observed partial correlation between genetics and ethnohistory, when geography is held constant. However, a randomization of records by location only results in reduced significance. Thus, while the historical sequence of the movements does not seem to matter in Europe, their geographic locations do. We discuss the implications of these findings. PMID- 8512055 TI - Reproductive activity of ruffed lemurs (Varecia variegata variegata) in a Madagascar rain forest. AB - Mating activity was observed during four breeding seasons in two groups of black and white ruffed lemurs (Varecia variegata variegata) living in lowland rain forest on Nosy Mangabe island, Madagascar. The onset of the May-July breeding season was signalled by behavioral changes in adult males. Males made forays outside their usual home ranges, were more aggressive to other males, and performed appetitive and other sex-specific behaviors more frequently. Females showed receptive and proceptive behaviors during a 1-2 day behavioral estrus. Ruffed lemurs mated monogamously, polyandrously, and polygynously. These observations do not support previous assertions that they live only in monogamous families. Limited evidence suggests females exercised mate choice and may have preferred familiar males. PMID- 8512056 TI - Comparative locomotor behavior of chimpanzees and bonobos: the influence of morphology on locomotion. AB - Results from a 10 month study of adult male and female bonobos (Pan paniscus) in the Lomako Forest, Zaire, and those from a 7 month study of adult male and female chimpanzees in the Tai Forest, Ivory Coast (Pan troglodytes verus), were compared in order to determine whether there are species differences in locomotor behavior and substrate use and, if so, whether these differences support predictions made on the basis of interspecific morphological differences. Results indicate that bonobos are more arboreal than chimpanzees and that male bonobos are more suspensory than their chimpanzee counterpart. This would be predicted on the basis of male bonobo's longer and more narrow scapula. This particular finding is contrary to the prediction that the bonobo is a "scaled reduced version of a chimpanzee" with little or no positional behavior difference as had been suggested. This study provides the behavioral data necessary to untangle contradictory interpretations of the morphological differences between chimpanzees and bonobos, and raises a previously discussed (Fleagle: Size and Scaling in Primate Biology, pp. 1-19, 1985) but frequently overlooked point--that isometry in allometric studies does not necessarily equate with behavioral equivalence. Several researchers have demonstrated that bonobos and chimpanzees follow the same scaling trends for many features, and are in some sense functionally equivalent, since they manage to feed and reproduce. However, as reflected in their morphologies, they do so through different types and frequencies of locomotor behaviors. PMID- 8512057 TI - Sex differences in adult chimpanzee positional behavior: the influence of body size on locomotion and posture. AB - Focal animal instantaneous sampling of adult male and female chimpanzee positional behavior was conducted during a 7-month study in the Tai Forest, Ivory Coast, in order to determine whether there are sex differences in the locomotion, posture, substrate use, and height preference of sexually dimorphic adult chimpanzees, and if so, whether these differences support predictions based on body size differences. Results indicate that as predicted, adult male and female chimpanzees differ in their arboreal locomotor behavior, with the larger males using less quadrupedalism and more climbing, scrambling, and aided bipedalism than females during feeding locomotion. There is a sex difference in height preference as well, with female chimpanzees consistently using more arboreal behavior than males, primarily during resting. Although it has been previously demonstrated that separate primate species of differing body size differ in locomotor and postural activities (Fleagle and Mittermeier, 1980; Crompton, 1984), this study clearly demonstrates that body size differences within a species can also be correlated with differences in locomotor behavior. These findings may influence how we interpret sex differences in body size of extinct species. PMID- 8512058 TI - Regulation of class II MHC gene expression by the inducible anti-sense RNA in transgenic mice. AB - We have established a gene regulatory system in mice by the inducible anti-sense RNA. We have generated transgenic mice carrying the anti-sense DNA composed of the class II MHC gene under the control of the human metallothionein IIa gene promoter. The detectable amount of anti-sense RNA was constitutively produced in spleen and bone marrow from transgenic mice and the amount in spleen was increased about fivefold by the stimulation of mice with heavy metal ions. We have previously reported that the reduction of class II MHC molecules on early B lineage cells by the anti-sense RNA results in delay of their development in the bone marrow culture. The early B cell development was slightly delayed in the culture from the transgenic mice. This delay was augmented in the culture by the addition of heavy metal ions in proportion to its concentration. These results suggest that the inducible anti-sense RNA reduces the expression of class II MHC molecules on B lineage cells. PMID- 8512059 TI - Establishment of hypoxic conditions for cultured monolayer cells: hypoxia in five minutes or less. AB - A versatile deaeration chamber for altering the gaseous environment of monolayer cell cultures has been developed. The design is such that multiple samples of radioactively labeled or unlabeled cells can be gassed simultaneously with a short period of time. Deaeration times to reduce the level of oxygen in initially aerated cellular medium to very low levels (less than 20 parts per million) were decreased at least 6- to 20-fold when compared to most other methods commonly used to achieve N2- or N2O-induced hypoxia. The application of this chamber in the investigation of radiation-induced cellular DNA strand breaks, which are very sensitive to the presence of oxygen, is described. The vessel should be useful for a variety of metabolic and physiologic experiments or cell, tumor, and radiation biology studies. PMID- 8512060 TI - Reagents for the preparation of chromophorically labeled polyethylene glycol protein conjugates. AB - We have developed a new class of reagents (2) for the covalent attachment of polyethylene glycol to proteins. These reagents (2) are the monomethoxypolyethylene glycol esters of 4-fluoro-3-nitrobenzoic acid. The reaction of 2 with lysine epsilon-amino groups produces a chromophore which can be used to quantitate the polyethylene glycol to protein molar ratio. Bovine (Zn, Cu) superoxide dismutase was used as a model protein for conjugation with 2. When monomethoxypolyethylene glycol of average molecular weight 2105 was used, a conjugate was obtained with a polyethylene glycol to protein molar ratio of 8.88 retaining 100% of native enzymatic activity; monomethoxypolyethylene glycol of average molecular weight 5210 yielded a conjugate with a polyethylene glycol to protein molar ratio of 9.96 retaining 73% of native enzymatic activity. PMID- 8512061 TI - Simultaneous determination of nerve-induced adenine nucleotides and nucleosides released from rabbit pulmonary artery. AB - Electrical field stimulation elicits the release of catecholamines, adenine nucleotides, and adenosine from the rabbit pulmonary artery in a frequency dependent manner. To enhance our ability to investigate the release of endogenous adenine nucleotides and adenosine from this and other biological preparations, a new analytical procedure has been developed. This procedure involves the use of an internal standard, 9-beta-D-arabinofuranosyladenine (IS), the derivatization of ATP, ADP, AMP, adenosine (Ado), and IS with chloroacetaldehyde, the isocratic high-performance liquid chromatographic separation of these ethenopurine derivatives on an Ultron N-phenyl HPLC column, and their detection and quantitation by fluorescence spectroscopy. This procedure has enhanced sensitivity and reliability over existing procedures due to the stability of the chromatographic baseline and the use of an internal standard. When this analytical procedure was utilized to measure the adenine nucleotides and Ado that are released from the rabbit pulmonary artery in response to electrical field stimulation, it was observed that the release of endogenous ATP, ADP, AMP, and Ado exceeded that of endogenous norepinephrine. A molar ratio (6-amino purines:catecholamines) of approximately 2000:1 was obtained at a stimulation frequency of 16 Hz. This observation suggests an important extracellular role for adenine nucleotides and nucleosides in the physiology of vascular tissues. PMID- 8512062 TI - Is n-pentane really an index of lipid peroxidation in humans and animals? A methodological reevaluation. AB - Volatile hydrocarbons such as ethane and n-pentane are known to originate from peroxidation of polyunsaturated fatty acids in membrane lipids and they are accepted as a sensitive and direct index of lipid peroxidation both in vitro and in vivo. Until now, an appropriate and commonly accepted method for the analysis of volatile hydrocarbons in exhalation air has not been described. We therefore developed a methodology for routine application in humans that is based on cryofocusing in combination with gas chromatography and is adaptable to mass spectrometry. The samples may be stored in stainless steel bombs up to 3 weeks, and sample volumes necessary to analysis are variable and can be adapted to analytical requirements. The interference by water and carbon dioxide, always present in excess, is strongly reduced. Mass spectroscopic analysis of exhalation air in human control subjects demonstrates, however, the presence of isoprene as the major constituent hitherto identified as n-pentane. The commonly used columns fail to separate n-pentane and isoprene. Based upon studies of the diverse methodologies reported in literature, it must be assumed that the reported responses of the gas chromatographic "n-pentane" peak in exhalation air of humans and animals, hitherto identified exclusively by authentic reference gases, are actually responses to isoprene or, at least, a mixture of both n-pentane and isoprene. PMID- 8512063 TI - Simultaneous preparation and quantitation of proteoglycans by precipitation with alcian blue. AB - Conditions for specific interaction between Alcian blue and proteoglycans were optimized by comparing the differential spectra of Alcian blue obtained with purified chondroitin sulfate dissolved in water with the spectra obtained with nasal cartilage proteoglycans dissolved in synovial fluid. A method was then designed that provides specific precipitation of proteoglycans or glycosaminoglycans in 4 M guanidine - HCl in the presence of protein, hyaluronic acid, or nucleic acids. The specificity is achieved by using a low pH in combination with detergent and high salt concentration. Stepwise addition of reagents is necessary to avoid binding of Alcian blue to proteins and nucleic acids. All polyanions, except polysulfates, are first neutralized by lowering the pH to 1.5. By including detergent in this step, the hydrophobic protein regions are blocked and not accessible for binding with the dye. These regions could otherwise bind Alcian blue by hydrophobic interaction. When the Alcian blue reagent is added after, only the polysulfated molecules will remain charged and free to interact with Alcian blue. At least 0.4 M guanidine-HCl is required to abolish the negative interference by proteins. All sulfated glycosaminoglycans are precipitated at 0.4 M guanidine-HCl. With increasing guanidine-HCl concentrations, the different glycosaminoglycans are precipitated in accordance with the critical electrolyte concentration of the respective glycosaminoglycan. The Alcian blue precipitation can be performed at different concentrations of guanidine-HCl in order to separate different classes of proteoglycans. Excess dye and contaminating proteins are removed by a wash in a DMSO-MgCl2 solution and the precipitate is dissolved in a mixture of guanidine-HCl and propanol. For quantitation, the absorbance is recorded in a microplate reader with the 600-nm filter, the assay being linear between 0.5 and 20 micrograms proteoglycan. Since no digestion of samples with protease is needed, the proteoglycans are recovered in native form. The proteoglycan-Alcian blue complexes dissociate in the guanidine-HCl/propanol mixture and the proteoglycans can be selectively precipitated with propanol. The dye is used for quantitation and the proteoglycans can be utilized for further analysis. PMID- 8512064 TI - Size-dependent separation of proteoglycans by electrophoresis in gels of pure agarose. AB - An improved system for electrophoresis of proteoglycans is presented, using a discontinuous buffer system that allows stacking of the sample. The molecular sieving in pure agarose was studied using cartilage proteoglycans separated into fractions of different size (Kav value) by gel chromatography. These fractions were used to establish the relationship between size and mobility in agarose gels of different concentrations. With low agarose concentration, the separation was largely dependent on charge density. With increasing agarose concentration, the separation became increasingly dependent on size. Electrophoresis provides a suitably sensitive tool for analysis of the proteoglycan and glycosaminoglycan fractions prepared by the Alcian blue precipitation described in the preceding paper. Alcian blue precipitated cartilage proteoglycans appeared identical in size to molecules prepared by conventional procedures when analyzed by electrophoresis. Proteoglycans of various sizes were prepared by precipitation with Alcian blue of 4 M guanidine-HCl extracts of bovine nasal cartilage, human articular cartilage, human skin, and bovine sclera. Proteoglycans were also precipitated from human synovial fluid and plasma. The samples were electrophoresed on 1.2% agarose gels, which was the highest agarose concentration suitable for large aggregating proteoglycans but still separating the smallest proteoglycans with one or two glycosaminoglycan chains from each other. Several sizes of proteoglycans were found in each sample except blood plasma, which only contained one small proteoglycan/glycosaminoglycan. Electrophoresis in agarose is also suitable for separating proteoglycan aggregates and monomers and allows rapid analysis of several samples at a time. The proteoglycans prepared by Alcian blue precipitation retained their ability to form aggregates with hyaluronic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512065 TI - Body plasma membrane vesicles from Paramecium contain a vanadate-sensitive Ca(2+) ATPase. AB - Paramecia are an excellent model system for studying the mechanisms involved in sensory transductions and intracellular Ca2+ regulation. These cells have two functionally distinct plasma membrane domains, body and cilia. The body plasma membrane is responsible for transduction of sensory stimuli into receptor potentials and the ciliary membrane is required for Ca2+ action potentials. Although ciliary membrane vesicles (cmv) have been purified and well characterized, body plasma membranes have not. We have generated body plasma membrane vesicles (bmv) by homogenization of deciliated cells and purified them from the microsome fraction by a two-phase aqueous polymer separation. The major criteria for purity of the bmv fraction are: (i) It is enriched 15-fold for a known plasma membrane marker (immobilization antigen) while the marker activities for other membranes were all decreased. The protein banding pattern of bmv is generally similar to cmv on SDS-PAGE. (ii) It contains a vanadate-sensitive Ca(2+)-ATPase activity that has been suggested to be a plasma membrane Ca2+ pump. The specific activity of this bmv Ca(2+)-ATPase is increased 4-fold over that of the homogenate. (iii) The phospholipid, fatty acid, and sterol composition of the bmv fraction are indicative of plasma membranes because they are qualitatively similar to cmv. The bmv also contains a membrane-bound NADPH-dependent cytochrome c reductase activity, suggesting that it may play a role in body plasma membrane function. This purified bmv preparation is useful for studying the role of the body plasma membrane in Ca2+ regulation, sensory transduction, protein and lipid trafficking, and plasma membrane fusion events. PMID- 8512066 TI - Directional coupling of synthetic peptides to poly-L-lysine and applications to the ELISA. AB - Synthetic peptides are increasingly being used as antigens to generate highly specific antisera. Screening the antipeptide sera by enzyme-linked immunosorbent assay (ELISA) can suffer from carrier crossreactivity or lack sensitivity due to poor adsorption or presentation of the peptides. In this work we describe a procedure utilizing a heterobifunctional crosslinker to effect the directional coupling of synthetic peptides to poly-L-lysine preadsorbed to microtiter plates. Plates prepared by this method conferred precision, sensitivity, and specificity to an ELISA for antipeptide antisera. In a competitive ELISA format this method permitted detection of specific peptides to 3.7 x 10(-10) M and provided an assay sensitive to protein structure in solution. PMID- 8512067 TI - A highly sensitive chromogenic microplate assay for quantification of rat and human plasminogen. AB - A simple and highly sensitive chromogenic microplate assay for quantification of rat and human plasminogen in plasma samples and subcellular fractions has been developed. The assay is based on a conversion of plasminogen to plasmin, using urokinase as an activator, and a subsequent cleavage of a chromogenic plasmin substrate D-alanyl-L-cyclohexylalanyl-L-lysine-p-nitroanilide-dihydroacet ate. p Nitroaniline being released by the cleavage is then measured at 410 nm with a microplate reader. The assay includes an acidification step to make plasminogen more readily activated to plasmin. The method is suitable for analyses of a large number of samples, measuring plasminogen in the nanogram range (0.5-50 ng/50 microliters of sample). PMID- 8512068 TI - Lactate oxidation for the detection of mitochondrial dysfunction in human skin fibroblasts. AB - To screen fibroblasts for defects in lactate/pyruvate oxidation, cells were grown to confluence in 25-cm2 flasks, rinsed, and incubated in glucose-free media containing 25 microM L-lactate and 0.1 microCi [D,L-1-14C]lactate. Lactate oxidation was measured as the amount of lactate oxidized in nmol of 14CO2 generated/mg protein/min. Fibroblasts from patients with mitochondrial or peroxisomal disorders had decreased lactate oxidation compared to the control (CON): CON, 1.9 +/- 0.13 nmol/mg/min; neonatal adrenoleukodystrophy (NALD), 0.45 +/- 0.01 (P < 0.001); rhizomelic chondrodysplasia punctata (RCDP), 0.13 +/- 0.002 (P < 0.001); mitochondrial defect of unknown etiology (MIT), 0.77 +/- 0.003 (P < 0.001); pyruvate dehydrogenase (PDH) deficiency, 0.98 +/- 0.02 (P < 0.001). This method is useful for screening fibroblasts for defects in lactate oxidation in patients with mitochondrial or peroxisomal disorders. Confirmation of the site of the defect may then be investigated with specific assays, e.g., PDH, in cellular homogenates: CON, 0.93 +/- 0.02 nmol/mg/min; NALD, 0.55 +/- 0.02; RCDP, 0.44 +/- 0.02; MIT, 0.53 +/- 0.03; PDH deficiency, 0.19 +/- 0.02. PMID- 8512069 TI - A radioimmunoassay-based method for measuring the true affinity of a monoclonal antibody with trace amounts of radioactive antigen: illustration with the products of a cell-free protein synthesis system. AB - This communication describes a novel highly sensitive method for measuring the affinity of a monoclonal antibody for its antigen. It is based on a radioimmunoassay in which the antigen is labeled with radioactivity. It is therefore particularly well adapted to the study of trace amounts of radiolabeled polypeptide chains produced either in vivo, or in vitro by a cell free protein synthesis system or by chemical radiolabeling. It offers several advantages over previously described methods. Though making use of insolubilized antibody, it does measure the true affinity constant of the monoclonal antibody in solution for the antigen. It can be used even when the antigen is present at concentrations far below the dissociation constant of the antibody/antigen complex. It does not require the antigen or the antibody to be purified. In most cases, it requires no sophisticated equipment. This method could be easily adapted to the determination of the equilibrium constant of any type of protein/ligand system. PMID- 8512070 TI - A continuous fluorescence assay of renin activity. AB - A sensitive fluorescence assay that employs a new fluorogenic peptide substrate has been developed to continuously measure the proteolytic activity of human renin. The substrate, DABCYL-gaba-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-EDANS, has been designed to incorporate the renin cleavage site that occurs in the N terminal peptide of human angiotensinogen. The assay relies upon resonance energy transfer-mediated, intramolecular fluorescence quenching that occurs in the intact peptide substrate. Efficient fluorescence quenching occurs as a result of favorable energetic overlap of the EDANS excited state and the DABCYL absorption, and the relatively long excited state lifetime of the EDANS fluorophore. Cleavage of the substrate by renin liberates the peptidyl-EDANS fragment from proximity with the DABCYL acceptor, restoring the higher, unattenuated fluorescence of the EDANS moiety. This leads to a time-dependent increase in fluorescence intensity, directly related to the extent of substrate consumed by renin cleavage. The kinetics of renin-catalyzed hydrolysis of this substrate have been shown to be consistent with a simple substrate inhibition model with a substrate Km approximately equal to 1.5 microM at physiological pH; Cleavage of the substrate occurs specifically at the Leu-Val bond and corresponds to the renin cleavage site of angiotensinogen, as reported earlier. In this report, we describe in detail the synthesis of the fluorogenic renin substrate and its application in assays of renin activity. Assay sensitivity has been evaluated by a series of enzyme dilution experiments using the continuous assay format, showing that the assay can detect renin as low as 30 ng/ml after a incubation of only 3-5 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512071 TI - Routine prostaglandin assay by GC-MS in multiwell tissue culture plates: application to human synoviocytes and chondrocytes. AB - Prostanoids can be assayed by the highly sensitive and reproducible gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) technique. This paper describes a simplified method applied to the quantification of prostaglandins (PG) in the supernatants of limited amounts of cells, cultured in multiwell plates (30,000 cells/well). The culture medium was extracted on C2 columns and the derivatization was performed in three steps. Prostanoids were then analyzed by GC-NICI-MS within 10 min. The storage conditions at each step were tested in order to achieve maximal yields. This procedure allowed the determination and quantification of PG produced by cultured human synovial cells and chondrocytes at the basal level as well as after interleukin-1 stimulation. PGE2, PGF2 alpha, and 6-keto-PGF1 alpha, the stable form of PGI2, were the main PG detected. Derivatization and GC-MS analyses of 18 samples could easily be performed in 1 day. The simplified GC-NICI-MS method can thus be routinely applied for assaying PG in any cell line cultured in multiwells. PMID- 8512072 TI - Charge heterogeneity of insulin fusion proteins expressed in Escherichia coli is not due to proteolytic degradation. AB - Evaluation of the yield of expression of exogeneous protein in transformed Escherichia coli cells by means of one-dimensional SDS-PAGE often leads to overestimation and miscalculation. For example, it is possible that proteins of similar size comigrate and thus mask the overexpressed product band. Therefore, two-dimensional electrophoresis was used to analyze two types of recombinant fusion proteins, i.e., a beta-galactosidase insulin fusion protein and a interleukin II insulin fusion protein, directly after fermentation. We found that production scale expression products show charge and size heterogeneity. The heterogeneous protein spots were characterized by subsequent blotting onto Immobilon membrane and by N-terminal sequencing. Some of the separated spots were either N-terminally blocked or already degraded to some extent. The integrity of the actual product component of the fusion protein was examined with a C-terminus specific antibody and by Western blot analysis of the 2D gels. PMID- 8512073 TI - A fluorometric deoxyribonucleic acid assay for tridimensional lattice cultures of fibroblasts. AB - A fast and sensitive in situ assay of deoxyribonucleic acid in miniaturized lattice cultures of fibroblasts is described. Tridimensional collagen and fibrin lattices prepared in 24-well plates were seeded with 50,000 to 200,000 cells. Cultures were fixed with formaldehyde, rinced with isopropanol, and dried. DNA assay was performed directly in the wells by addition of 3,5-diaminobenzoic acid (DABA) reagent. A calibration curve was prepared with calf thymus DNA. Fluorescence of DNA-DABA was evaluated after 45 min incubation (excitation wavelength 420 nm, emission wavelength 490 nm). The method showed linear results from 0.5 to 10 micrograms DNA and proved sensitive for low cell numbers (50,000 per dish). DNA assay in monolayers and in different types of lattices showed that comparable results were obtained in the different models without interference of the extracellular matrix. This technique is regarded as a costless and efficient tool for evaluating the number of cells in lattices in basal conditions or under pharmacological stimulation. PMID- 8512074 TI - Resolving power: a quantitative measure of electrophoretic resolution. AB - Resolving power is a quantitative measure of the ability of an electrophoretic system to separate DNA (and other) molecules of similar size. It is a dimensionless quantity, and hence facilitates comparison of the performance of electrophoretic systems that operate very differently. Resolving power can be determined as a function of molecular length from experimental data consisting of a series of completely resolved bands on a gel or blot; closely spaced bands are not required. We discuss factors such as the mass of DNA in a particular band and the spatial resolution of the system used to image the distribution of DNA on a gel or blot that, while not an intrinsic part of the electrophoretic system, may influence the observed resolving power. We derive an empirical global dispersion function that applies both to images of gels obtained after a fixed time of electrophoresis of all the samples and to images obtained as each species reaches a detector located at a fixed distance from the starting well. We use this dispersion function to show that the improvement in resolving power produced by extending the time or distance of electrophoresis in a static, uniform electric field asymptotically approaches a limiting value that is a function of the length of the DNA. When plotted as a function of molecular length, this limiting value defines an envelope that characterizes the intrinsic limits of performance of a particular electrophoretic system (e.g., electric field strength, gel type and concentration, buffer, temperature). Comparing the resolving power of static field agarose gel electrophoresis as routinely practiced for separating DNA molecules from 10(3) to 10(5) bp long with other electrophoretic schemes suggests that significant improvements should be achievable. PMID- 8512075 TI - Capillary electrophoretic separation of human recombinant erythropoietin (r HuEPO) glycoforms. AB - Free zone capillary electrophoresis was investigated for the separation of glycoforms in recombinant erythropoietin (r-HuEPO). Reduction of electroendoosmotic flow through the addition of 1,4-diaminobutane and in the presence of urea resulted in optimum separation of all of the major glycoforms. Incubation of r-HuEPO with neuraminidase caused the slowest migrating species to diminish first in response, indicating that these contained the highest numbers of sialic acids. Additional evidence was obtained from spiking r-HuEPO with individual glycoforms isolated by preparative isoelectric focusing. These results indicate that the separation occurs in a predictable manner in order of increasing number of sialic acids contained in the glycoforms. As a consequence, the electropherograms provide the same information as that obtained from conventional gel isoelectric focusing, although separating by a different mechanism. PMID- 8512076 TI - Quantification of chemiluminescent DNA probes using liquid scintillation counting. AB - A novel method for quantifying chemiluminescent DNA probes is described. The method uses liquid scintillation counting to measure light emission from the alkaline phosphatase-catalyzed breakdown of the substrate PPD (3-(4 methoxyspiro[1,2-dioxetane-3,2'-tricyclo[3.3.1.1 (3.7[decan]- 4-yl)phenyl phosphate) on dot blot preparations. Serial dilutions of either pUC18 DNA or lambda DNA were hybridized with digoxigenin-labeled probes and detected using the method described. Light flux (luminescence) was linearly related to DNA concentration, typically with a coefficient of determination (r2) of 0.9 or better. Due to the stability of alkaline phosphatase and the long-lived luminescence of PPD in the Lumi-phos formulation, repetitive analyses of a given sample can be made for up to 20 h. The method can reliably detect 17 amol of DNA (30 pg pUC18DNA) with a coefficient of variation on replicate samples of 14%. Optimization experiments showed that 7% sodium dodecyl sulfate in the prehybridization and hybridization buffers resulted in the lowest background; the best combination of signal-to-noise ratio and reproducibility was obtained using Bio-Rad Zeta-Probe GT nylon membranes. Direct immersion of samples into a solution of substrate was found to give the most precise results and ensured that substrate limitation at high concentrations of alkaline phosphatase (i.e., higher DNA amounts) did not occur. PMID- 8512077 TI - Analysis of ginsenosides by chromatography and mass spectrometry: release of 20 S protopanaxadiol and 20 S-protopanaxatriol for quantitation. AB - To facilitate studies on the possible presence of ginseng products in serum, tissues, and excretions, a procedure to optimize the analysis of the ginseng specific products, i.e., ginsenosides, had to be worked out. With the present method the two sapogenins, 20S-protopanaxadiol and 20S-protopanaxatriol, can be produced from ginsenosides Rb1, Rc, Rd, Re, and Rg1 in 80% yield by using an improved alkaline cleavage procedure. In contrast to previously described acid hydrolysis procedures for ginsenosides, our alkaline conditions caused no epimerization, no hydroxylation, and no cyclization of the side chain. Furthermore, no unchanged ginsenosides were recovered. The products of alkaline and acidic cleavage were separated, identified, and characterized by GC, GC-MS, and HPLC. In contrast to alkaline cleavage, treatment with acid afforded a number of side products. The C-20S-epimers of the ginseng sapogenins could be distinguished from C-20R epimers by difference in mass spectra and retention time after trimethylsilylation. PMID- 8512078 TI - Preparation of tritium-labeled antibiotic, cerulenin, by two-phase system. PMID- 8512079 TI - A batch elution procedure for assaying adenylate cyclase. PMID- 8512080 TI - Rapid assay of aromatase activity by fast liquid chromatography: spectroscopic evaluation of metabolite profiles indicate unexpected pitfalls. PMID- 8512081 TI - Separation of glycopeptides from in vitro O-glycosylation reactions using C18 cartridges. PMID- 8512082 TI - Determination of the tryptophan:tyrosine ratio in proteins. PMID- 8512083 TI - Suitability of reverse-phase columns from different sources for separation of uric acid from its oxidation products. PMID- 8512085 TI - The percentage of nerve cell bodies arranged in clusters decreases with age in the spinal ganglia of adult rabbits. AB - In the spinal ganglia of the rabbit the nerve cell bodies, which in early developmental stages are mutually in contact, come to be completely isolated from each other by a satellite cell sheath and by a connective envelope before birth. The present study demonstrates that in the early postnatal months some nerve cell bodies are still arranged in clusters, and that the percentage of these decreases progressively throughout adult life. This decrease probably arises because in some of the ganglion neurons the process of envelopment of the perikaryon by an individual sheath begins later, or takes place more slowly, than in the majority of cases. Therefore, the relationship between neurons and between neurons and satellite cells may change in certain clusters of nerve cell bodies under normal circumstances during adult life. PMID- 8512084 TI - Functional neuroanatomy and neuropathology of the human hypothalamus. AB - The human hypothalamus is involved in a wide range of functions in the developing, adult and aging subject and is responsible for a large number of symptoms of neuroendocrine, neurological and psychiatric diseases. In the present review some prominent hypothalamic nuclei are discussed in relation to normal development, sexual differentiation, aging and a number of neuropathological conditions. The suprachiasmatic nucleus, the clock of the brain, shows seasonal and circadian variations in its vasopressin neurons. During normal aging, but even more so in Alzheimer's disease, the number of these neurons decreases. In homosexual men this nucleus is larger than in heterosexual men. The difference between the sexually dimorphic nuclei of men and women arises between the ages of 2-4 to puberty. In adult men this nucleus is twice as large as in adult women. In the process of aging, a sex-dependent decrease in cell number occurs. The vasopressin and oxytocin cells of the supraoptic and paraventricular nucleus are present in adult numbers as early as mid-gestation. Lower oxytocin neuron numbers are found in Prader-Willi syndrome, AIDS and Parkinson's disease. Familial hypothalamic diabetes insipidus is based upon a point mutation in the vasopressin neurophysin-glycopeptide gene. Parvicellular corticotropin-releasing hormone containing neurons in the paraventricular nucleus increase in number and are activated during the course of aging. In post-menopausal women, the infundibular or arcuate nucleus contains hypertrophic neurons containing oestrogen receptors. These neurons may be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis may be involved in feeding behaviour and metabolism. In Huntington's disease the majority of its neurons is lost; in Alzheimer's disease it shows very strong cytoskeletal alterations. Tuberomammillary nucleus neurons contain, e.g., histamine or galanine, and project to the cortex. Strong cytoskeletal changes, as well as plaques and tangles are found in this nucleus in Alzheimer's disease. The various hypothalamic nuclei are probably involved in many functions and symptoms of which only a minority has been revealed. PMID- 8512087 TI - Muscle growth and myosin isoform transitions during development of a small teleost fish, Poecilia reticulata (Peters) (Atheriniformes, Poeciliidae): a histochemical, immunohistochemical, ultrastructural and morphometric study. AB - The myosin composition of lateral muscle in Poecilia reticulata from birth to adult was studied by ATPase histochemistry and immunostaining with myosin isoform specific antibodies. At birth the muscle consists of two layers containing developmental isoforms of myosin. In deep layer fibres the developmental myosin is replaced by the adult fast-white isoform soon after birth. In the epaxial and hypaxial monolayer fibres the myosin composition present at birth (J1) is replaced within 3 days by another (J2). In some fibres, this J2 composition is retained in the adult, but in others it is slowly replaced by the adult slow-red muscle isoform. Close to the lateral line, all monolayer fibres are already in transition between the J2 myosin and the adult slow-red form at birth, and rapidly complete the transition to slow-red form. These fibres, together with others generated de novo in an underlying hyperplastic zone, form the red muscle layer of the adult. The pink muscle develops during the first month after birth, and by 31 days it consists of an outer, middle and inner layer. A few middle layer fibres are already present at birth, while the outer layer fibres first appear 3 days after birth. The thin inner layer is probably a transitional form between the middle pink and adult white types, and appears at about 31 days. A morphometric analysis showed that growth of the white muscle occurs principally by hypertrophy. Even at the magnification level of the electron microscope, no satellite cells or myoblasts which could give rise to new fibres were found in the white muscle, except in the far epaxial and hypaxial regions and only in the first 10 days. A zone of hyperplastic growth was also found lying just under the superficial monolayer close to the lateral line, and this presumably contributes fibres to the red and pink muscle layers. PMID- 8512086 TI - Fetal antigen 1 (FA1) in the human pancreas: cell type expression, topological and quantitative variations during development. AB - Monospecific rabbit anti-human fetal antigen 1 (FA1), was used to examine the distribution of FA1 during the development of the human fetal pancreas and liver using an indirect immunoperoxidase technique. FA1 was expressed by 94% of the glandular epithelial cells of the branching ducts in the pancreatic anlage at week 7 of gestation. This pattern changed during the development of the human pancreas, 64% of the glandular cells being FA1 positive at week 17 of gestation, decreasing to 11% in the infant (4 months after birth). In the infant and adults the FA1 expression was restricted to a subpopulation of beta-cells within the islets of Langerhans. Insulin immunoreactive cells were scattered throughout the epithelium of primitive branching pancreatic ducts at week 7 of gestation, well before the formation of islets. From the 7th through to the 17th week of gestation, FA1 was found in the cytoplasm of fetal hepatocytes, whereas no staining was observed in the liver from a 4-month-old infant. No FA1 expression was found in the epithelium of the developing gut. The present findings indicate that the glandular epithelial cells in the developing pancreas may serve as stem cells, which, if appropriately induced, may differentiate into endocrine cells. Fetal antigen 1 (FA1) may take part in or be a result of this differentiation. PMID- 8512088 TI - Protein-synthesis inhibition induces perichromatin granule accumulation and intranuclear rodlet formation in osmotically stimulated supraoptic neurons. AB - The distribution of perichromatin granules (PGs), a storage form of pre-mRNAs, was studied in supraoptic neurons of control and osmotically stimulated rats, and also after treatment with cycloheximide, a protein-synthesis inhibitor. In non cycloheximide-treated rats, neuronal activation by dehydration significantly decreased the number of PGs. Conversely, PGs were drastically increased in the supraoptic neurons of dehydrated rats treated with cycloheximide for 4 h. This suggests that cycloheximide does not interfere with the transcriptional activation induced by dehydration, but it affects the processing of newly synthesized pre-mRNAs. Moreover, protein-synthesis inhibition was associated with the formation of intranuclear bundles of tubular filaments. PMID- 8512089 TI - The Splotch (Sp1H) and Splotch-delayed (Spd) alleles: differential phenotypic effects on neural crest and limb musculature. AB - Homozygous mutants of the murine Splotch (Sp1H) and the Splotch-delayed (Spd) alleles show different phenotypes with respect to neural crest derivatives and their longevity. In this report, Sp1H/Sp1H, Spd/Spd and Sp1H/Spd mouse mutant embryos were examined histologically in serial sections on day 13.5 of gestation. All Spd/Spd and Sp1H/Spd embryos showed a similarly dramatic reduction of the muscle primordia in the limbs that had previously been observed in Sp1H homozygotes. The neural crest-derived spinal ganglia and Schwann cells showed major defects in Sp1H homozygotes and lesser defects in Spd homozygote, with Sp1H/Spd embryos being intermediary. Also, the neural crest-derived septum of the truncus arteriosus was formed in almost none of the Sp1H homozygotes, in roughly half of the Sp1H/Spd double heterozygotes and in all of the Spd homozygotes. Aortic conus malformations were observed in all mutants. The paternal origin of the Sp1H allele in the Sp1H/Spd embryos had no influence on the resulting phenotype. These observations demonstrate that the neural tube defect and the limb muscle defect are the common denominator of both the Splotch and the Splotch delayed phenotype. The extent of the neural crest defects in the mutant compounds apparently depends on the Splotch alleles involved. PMID- 8512090 TI - Action of estradiol and tamoxifen on the Mullero-regressive activity of the chick embryonic testis assayed in vivo by organotypic grafting. AB - In the chick, the implantation of a testis graft from a 13-day-old male donor embryo into the extra-embryonic coelom of 3-day-old female embryos induces the total regression of their Mullerian ducts because of the anti-Mullerian hormone (AMH or MIS) secreted by the implant. Pre-treatment of the donors with estradiol (E2), between day 12 and day 13, counteracts in a significant way the Mullero regressive activity of the implant. Co-treatment of donors at the same stage with both Tamoxifen (TAM) and E2 restores the initially observed activity, thus demonstrating the presence of Tamoxifen-sensitive estrogen receptors at the late stage of treatment in the Sertoli cells responsible for AMH secretion. The treatment of 3-day-old male donor embryos with E2 causes the differentiation of their left gonad into an ovotestis which provides implants totally devoid of Mullero-regressive activity. The additional treatment with TAM of the grafted host embryos, does not modify the results obtained when E2-treated male gonads are grafted to host embryos not treated with TAM. This shows that the lack of Mullero-regressive activity exhibited by the E2-treated male gonads does not depend on the estrogens they may secrete during the time of the assay, i.e., it cannot be attributed to a protecting action of estrogens on the MDs of the host. Our results therefore favor the idea that E2 down-regulates AMH. The relevance of such a regulation to the phenomenon of Mullerian duct maintenance, either in the E2-feminized male or in the female chick embryo, is discussed. PMID- 8512091 TI - Astroglial pattern in the spinal cord of the adult barbel (Barbus comiza). AB - The distribution and the structural, ultrastructural and immunohistochemical characteristics of the astroglial cells in the spinal cord of the adult barbel (Barbus comiza) have been studied by means of metallic impregnations (Golgi and gold-sublimate), immunohistochemical (GFAP and vimentin) and electron microscopic techniques. GFAP-positive cells were mainly distributed in the ependyma and in the periependymal region, but they have also been observed at subpial level in the anterior column. The ependymocytes were heterogeneous cells because they showed different immunohistochemical characteristics: GFAP-positive, vimentin positive or non-immunoreactive cells. The radial astrocytes showed only GFAP immunoreactivity, and their processes ended at the subpial zone forming a continuous subpial glia limitans. Desmosomes and gap junctions between somata and processes of radial astrocytes were numerous, and a relationship between radial astroglial processes and the nodes of Ranvier was also described. The perivascular glia limitans was poorly developed and it was not complete in the blood vessels of the periependymal zone; in this case, the basal lamina was highly developed. An important characteristic in the barbel spinal cord was the existence of a zone with an abundant extracellular space near the ependyma. The presence of radial astroglial somata at subpial level, the existence of vimentin positive ependymocytes and the abundant extracellular space in the periependymal zone is discussed in relation to the regeneration capacity and the continuous growth showed by fish. Moreover, the abundance of gliofilaments and desmosomes leads us to suggest that mechanical support might be an important function for the astroglial cells in the barbel spinal cord. PMID- 8512092 TI - Differential effects of neonatal denervation on intrafusal muscle fibers in the rat. AB - The response of developing muscle spindles to denervation was studied by sectioning the nerve to the medial gastrocnemius muscle of rats at birth. The denervated spindles were examined daily throughout the first postnatal week for changes in ultrastructure and expression of several isoforms of myosin heavy chain (MHC). Each of the three different types of intrafusal muscle fiber exhibited a different response to denervation. Within 5 days after the nerve section nuclear bag2 fibers degenerated completely; nuclear bag1 fibers persisted, but ceased to express the 'spindle-specific' slow-tonic MHC isoform and thereby could not be differentiated from extrafusal fibers; nuclear chain fibers did not form. The capsules of spindles disassembled, hence spindles or their remnants could no longer be identified 1 week after denervation. Neonatal deefferentation has little effect on these features of developing spindles, so removal of afferent innervation is presumably the factor that induces the loss of spindles in denervated muscles. Degeneration of the bag2 fiber, but not bag1 or extrafusal fibers, reflects a greater dependence of the bag2 fiber than the bag1 fiber on afferent innervation for maintenance of its structural integrity. This difference in response of the two types of immature bag fiber to denervation might reflect an origin of the bag2 fibers from a lineage of myogenic cells distinct from that giving rise to bag1 or extrafusal fibers, or a difference in the length of contact with afferents between the two types of bag fiber prior to nerve section. PMID- 8512093 TI - New frontiers in anesthesia research. Assessing the impact of practice patterns on outcome, health care delivery, and cost. PMID- 8512094 TI - A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. AB - BACKGROUND: Different anesthetic agents have different effects on cerebrovascular physiology. However, the importance of these differences in neuroanesthetic practice are unclear. In an effort to determine whether important clinical differences are present, the authors compared three anesthetic techniques in 121 adults undergoing elective surgical removal of a supratentorial, intracranial mass lesion. METHODS: Patients were assigned randomly to one of three groups. In group 1 (n = 40), anesthesia was induced with propofol and maintained with fentanyl (approximately 10 micrograms/kg load, 2-3 micrograms.kg-1.h-1 infusion) and propofol (50-300 micrograms.kg-1.min-1). In group 2 (n = 40), anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide. Up to 2 micrograms/kg fentanyl was given after replacement of the bone flap. In group 3 (n = 41), anesthesia was induced with thiopental and maintained with fentanyl (approximately 10 micrograms/kg load, 2-3 micrograms.kg-1.h-1 infusion), nitrous oxide, and low-dose isoflurane, if required. Blood pressure, heart rate, expired gas concentrations, and ventilatory parameters were recorded automatically in all patients. Epidural intracranial pressure (ICP) was measured via the first burr hole, brain swelling was rated at the time of dural opening, and emergence was monitored closely. Preoperative computed tomography or magnetic resonance imaging scans were evaluated, and pre- and postoperative neurologic exams were performed by a neurosurgeon unaware of group assignments. Total hospital stay (days) and total hospital cost (exclusive of physician charges) also were reviewed. RESULTS: During induction, higher heart rates were seen in isoflurane/nitrous oxide patients, whereas mean arterial pressure was approximately 10 mmHg less during the maintenance phase (compared with both other groups). Otherwise, there were few intergroup hemodynamic differences. While there were no clinically important intergroup differences in mean ICP (+/- SD)-group 1, ICP = 12 +/- 7 mmHg; group 2, 15 +/- 12 mmHg; group 3, ICP = 11 +/- 8 mmHg-more isoflurane/nitrous oxide patients (nine, group 2) had an ICP > or = 24 mmHg than in the other groups (two each). Emergence was, overall, more rapid with fentanyl/nitrous oxide. For example, the median time until the patient could be awakened by quiet verbal command, e.g., "Open your eye," was 5 min, versus 10 min in the other groups. There were no relationships between ICP and any measurement of emergence (e.g., time to response to commands). Seven of 41 (17%) fentanyl/nitrous oxide patients vomited in the early postoperative period, compared with only 1 of 40 (2.5%) of those given propofol/fentanyl and 2 of 40 (5%) receiving isoflurane/nitrous oxide (P = 0.03). There were no differences in the incidence of new postoperative deficits, total hospital stay, or cost. CONCLUSIONS: Although there are modest differences among the three tested anesthetics, short-term outcome was not affected. These results indicate that, despite their respective cerebrovascular effects, all of the anesthetic regimens used were acceptable in these patients undergoing elective surgery. PMID- 8512095 TI - Inhaled nitric oxide. Selective pulmonary vasodilation in cardiac surgical patients. AB - BACKGROUND: Inhaled nitric oxide (NO), an endothelium-derived relaxing factor, is a selective pulmonary vasodilator. The authors investigated whether the pulmonary vasodilation resulting from 20 ppm inhaled NO is related to the degree of pulmonary hypertension or affected by cardiopulmonary bypass (CPB) or the presence of intravenous nitrates. METHODS: In patients undergoing cardiac surgery (n = 20) or in whom the circulation was supported with a ventricular assist device (VAD; n = 5), the lungs were ventilated with 80% O2 and 20% N2 followed by the same gas concentrations containing 20 ppm NO for 6 min. RESULTS: Inhaled NO decreased (P < 0.05) the pulmonary artery pressure from 36 +/- 3 to 29 +/- 2 mmHg and 32 +/- 2 to 27 +/- 1 mmHg, before and after CPB, respectively, and from 68 +/ 12 to 55 +/- 9 mmHg in patients with a VAD. Similarly, the pulmonary vascular resistance (PVR) decreased (P < 0.05) from 387 +/- 44 to 253 +/- 26 dyne.cm.s-5 and 260 +/- 27 to 182 +/- 18 dyne.cm.s-5, before and after CPB, respectively, and from 1,085 +/- 229 to 752 +/- 130 dyne.cm.s-5 in patients with a VAD. Central venous pressure, cardiac output, systemic hemodynamics, and blood gases did not change after inhalation of NO before or after CPB, whereas arterial oxygen tension, mixed venous hemoglobin saturation, and mean arterial pressure increased (P < 0.05) in patients supported with a VAD. All hemodynamic and laboratory data returned to control 6 min after discontinuation of NO. The decrease in PVR was proportional to baseline PVR (delta PVR = -0.45 PVRb + 39.9) before CPB. The pre- and post-CPB slopes were identical despite possible damage to the endothelium resulting from CPB and the post-CPB presence of intravenous nitroglycerin (17 of 20 patients). CONCLUSIONS: This study demonstrates that 20 ppm inhaled NO is a selective pulmonary vasodilator in cardiac surgical patients before and after CPB and in patients in whom the circulation is supported with a VAD. Furthermore, NO induced pulmonary vasodilation is proportional to PVRb and does not appear to be altered by CPB, the presence of a VAD, or infusion of nitrates. PMID- 8512096 TI - Pharmacodynamics of alfentanil as a supplement to propofol or nitrous oxide for lower abdominal surgery in female patients. AB - BACKGROUND: Although propofol and alfentanil are given in combination in clinical practice, the pharmacodynamic interaction between these drugs has not been described. METHODS: The pharmacodynamics of alfentanil when given as a supplement to propofol were studied in 10 ASA physical status 1 female patients (group P) undergoing lower abdominal surgery and compared to the pharmacodynamics of alfentanil when given as a supplement to nitrous oxide (group N, n = 10). Anesthesia was induced by either computer-controlled infusion of propofol and alfentanil at target concentrations of 3 micrograms/ml and 100 ng/ml (group P) or computer-controlled infusion of 400 ng/ml alfentanil as a supplement to nitrous oxide and oxygen (ratio 2:1; group N). The target concentration of alfentanil was varied to patient responses, and the nitrous oxide and propofol concentrations were maintained constant. A sigmoid Emax model was fitted to response/no response data versus plasma alfentanil concentrations at intubation, skin incision, and the opening of the peritoneum in both groups and for the intraabdominal part of surgery in the individual patients. In addition, the speed of recovery in both groups was determined by a deletion-of-p's test. RESULTS: The EC50 (the concentration at which, with a 50% probability, the patients did not respond to the surgical stimuli) of alfentanil during propofol anesthesia was 92 ng/ml for intubation, 55 ng/ml for skin incision, 84 ng/ml for the opening of the peritoneum, and 66 +/- 38 ng/ml (mean +/- SD) for the intraabdominal part of surgery. The corresponding values during nitrous oxide anesthesia were significantly higher: 429 ng/ml for intubation, 101 ng/ml for skin incision, and 206 +/- 65 ng/ml for the intraabdominal part of surgery (P < 0.001). The speed of recovery was similar in both groups. CONCLUSIONS: The alfentanil requirements in ASA physical status 1 female patients undergoing lower abdominal surgery are less when given as a supplement to propofol (4 micrograms/ml) compared to 66% N2O. PMID- 8512097 TI - Physiologic responses to hyperthermia during epidural anesthesia and combined epidural/enflurane anesthesia in women. AB - BACKGROUND: During combined epidural/isoflurane anesthesia, the core temperature triggering finger-tip vasoconstriction is approximately 1 degree C less than that triggering redilation. This hysteresis suggests that thermoregulatory responses are not dependent entirely on current thermal status (state-dependence), but may be influenced also by the system's recent thermal history (direction-dependence). Once triggered, the gain and maximum response intensity of many thermoregulatory responses is nearly normal during isoflurane anesthesia. However, it remains unknown whether preserved gain and maximum response intensities are a characteristic paradigm describing thermoregulatory responses to general anesthetics. Also unknown is whether the sweating and pre-capillary vasodilation thresholds are comparably impaired by different volatile anesthetics. Accordingly, the authors tested the hypotheses that, during one minimum alveolar concentration of enflurane anesthesia: (1) there is a direction-dependent hysteresis for sweating; (2) the sweating and active vasodilation thresholds increase approximately 1.2 degrees C, as they do during one minimum alveolar concentration of isoflurane; and (3) the gain and maximum intensity of sweating are well preserved. METHODS: Six female volunteers each were studied on 2 days, once during epidural anesthesia alone and once with combined enflurane (1.7%)/epidural anesthesia. On each study day, core hyperthermia was induced by cutaneous warming restricted to the legs. Warming continued until chest sweating reached maximal values; the volunteers then were cooled gradually until sweating stopped. The core temperature at which the sweating rate departed from baseline values was considered the activation threshold. Gain was expressed as the slope of the sweating rate versus core temperature curve within the range 25-75% of the maximum sweating rate. Hysteresis was evaluated by subtracting the tympanic membrane temperature at which the sweating rate suddenly increased during warming (approximately 25% above baseline values) from that at which sweating precipitously decreased during cooling (approximately 75% of maximum values). RESULTS: The sweating threshold was 1.4 +/- 0.7 degrees C higher during combined enflurane/epidural anesthesia than during epidural anesthesia alone. Maximum intensity was approximately 700 g.m-2.h-1, and the gain approximately 1,300 g.m 2.h-1.degrees C-1 during each treatment. No hysteresis was detected on either study day. CONCLUSIONS: One minimum alveolar concentration of enflurane increased the sweating threshold only slightly more than previously reported for isoflurane. As in previous studies of sweating and vasoconstriction during isoflurane anesthesia, gain and maximum response intensity were well preserved during enflurane anesthesia. An increase in the interthreshold range (temperatures not triggering thermoregulatory responses), with little change in gain and maximum response intensities, appears to be the typical effect of volatile anesthetics. Sweating during enflurane anesthesia appears to be state dependent and little influenced by the direction of core temperature perturbations. PMID- 8512098 TI - Heat loss during surgical skin preparation. AB - BACKGROUND: Hypothermia develops rapidly during the 1st h of anesthesia and results in part from evaporative heat loss during surgical skin preparation. The authors tested the hypothesis that evaporation of skin preparation solution contributes significantly to hypothermia. METHODS: Five healthy, unanesthetized volunteers were studied in a 22 +/- 0.4 degrees C environment. One thigh of each volunteer was washed for 10 min, using each of the following representative solutions: (1) water; (2) 50% ethanol in water (EtOH/H2O; similar to tincture of iodine); and (3) povidone-iodine gel. Water and EtOH/H2O each were tested at ambient temperature (cold), warmed to 40 degrees C before application (warm), and with radiant heating of the skin, and gel only at ambient temperatures, resulting in seven study states. Heat loss and skin temperatures on the washed thighs were measured using thermal flux transducers, and values compared with the data obtained from the contralateral unwashed thighs. Change in mean body temperature (per 70 kg) due to washing was calculated by integrating measured heat loss over time and multiplying by the specific heat of human tissue. A mathematical model was developed to predict cutaneous heat loss using only skin temperature, independent of the type and temperature of skin-preparation solution or the use of radiant heating during preparation. RESULTS: Heat loss from the unwashed thigh was approximately 14 kcal/m2 during radiant warming and approximately 39 kcal/m2 without warming. Net heat loss (increment produced by washing) was approximately 30 kcal/m2 with water and gel without radiant warming, but loss was larger with EtOH/H2O than with water under all study conditions. Radiant warming reduced total heat loss (increment produced by washing and environment) during both the EtOH/H2O and water trials, compared with warm or cold EtOH/H2O and water alone. The calculated decreases in mean body temperature per 70 kg ranged from -0.2 to 0.7 degree C/m2. The smallest decrease occurred during radiant warming and washing with water, and the largest decreases during warm or cold EtOH/H2O. CONCLUSIONS: Heat loss was significantly less with water-based than with alcohol based solutions. Though heating the solutions and radiant warming decreased heat loss, such loss under each tested condition, even per square meter of washed surface, was small compared to other causes of perioperative hypothermia. Consequently, the authors recommend that efforts to maintain intraoperative normothermia be directed elsewhere. PMID- 8512099 TI - Intramuscular dexmedetomidine as premedication for general anesthesia. A comparative multicenter study. AB - BACKGROUND: Dexmedetomidine is a new potent and selective alpha 2-agonist that might prove useful as a preanesthetic agent. METHODS: A randomized, double-blind study design was used in 192 ASA physical status 1 and 2 patients scheduled for elective abdominal hysterectomy, cholecystectomy, or intraocular surgery under general anesthesia. Intramuscular injection of 2.5 micrograms/kg dexmedetomidine administered 60 min before and intravenous saline placebo 2 min before induction of anesthesia (DEXPLA group, n = 64) was compared with a combination of 0.08 mg/kg intramuscular midazolam 60 min and 1.5 micrograms/kg intravenous fentanyl 2 min before induction (MIDFENT group, n = 64), or a combination of intramuscular dexmedetomidine and intravenous fentanyl (DEXFENT group, n = 64). After thiopental induction, anesthesia was maintained with 70% N2O/O2, and fentanyl was administered according to clinical and cardiovascular criteria. Patients undergoing cholecystectomy received additional enflurane. RESULTS: Dexmedetomidine and midazolam induced comparable preoperative sedation and anxiolysis. The DEXFENT combination blunted the increases in blood pressure and heart rate induced by tracheal intubation more efficiently when compared with the DEXPLA and MIDFENT groups, in which approximately 25 mmHg and 15 beats/min greater increases were observed. The intraoperative fentanyl requirements were greater in MIDFENT patients when compared with both dexmedetomidine groups, in which 56% (DEXFENT group) and 31% (DEXPLA group) less fentanyl, respectively, was needed. Intraoperatively, fluids or vasopressors for hypotension and glycopyrrolate for bradycardia were administered more often to patients receiving dexmedetomidine than to those who did not. Postoperatively, there were no differences in oxygen saturation, analgesic, or antiemetic requirements, but dexmedetomidine-induced blood pressure and heart rate reductions were still evident at the end of the 3-h follow-up period. Bradycardia as an adverse event was reported more frequently in dexmedetomidine patients (20% in the DEXPLA and 33% in the DEXFENT groups) than in MIDFENT patients (8%). CONCLUSIONS: The results suggest that pretreatment with a single intramuscular injection of 2.5 micrograms/kg dexmedetomidine is efficacious, but significantly increases the incidence of intraoperative hypotension and bradycardia in ASA physical status 1 or 2 patients. PMID- 8512100 TI - Are all preterm infants younger than 60 weeks postconceptual age at risk for postanesthetic apnea? AB - BACKGROUND: Preterm and ex-preterm infants are at risk for life-threatening apnea after general anesthesia. The authors attempted to define the postconceptual age beyond which apnea is less likely to occur and to identify the factors that predispose to postanesthetic apnea. METHODS: Ninety-one infants younger than 60 weeks postconceptual age undergoing 101 general anesthetics were prospectively studied. All infants were admitted to the hospital for cardiorespiratory monitoring overnight. The presence of coexistent medical conditions that could influence the incidence of apnea was determined by a review of current and previous medical records and by history. RESULTS: Of 38 procedures performed in 35 infants younger than 44 weeks postconceptual age, 10 (26.3%) procedures in 9 infants were associated with postanesthetic apnea. In eight of these, apnea did not resolve spontaneously: four infants required stimulation, and four required continuous positive airway pressure by face mask. Apnea occurred after 2 of 63 procedures performed in infants 44 weeks postconceptual age or older. Both episodes occurred in one patient who had neurologic disease. Of the remaining 61 procedures in the latter age group, 7 were associated with episodes of bradycardia (lowest heart rate was 79 beats/min) postoperatively without apnea. These episodes lasted up to 5 s, were not associated with apnea or cyanosis, and resolved spontaneously in all cases. All infants with postanesthetic apnea and/or bradycardia experienced their first episode within 12 h after surgery. CONCLUSIONS: Ex-preterm infants younger than 44 weeks postconceptual age are at greater risk for apnea after general anesthesia than are infants older than 44 weeks postconceptual age. Based on these results, the maximum long-run risk of postanesthetic apnea in preterm infants older than 44 weeks postconceptual age is 5% with 95% confidence. PMID- 8512101 TI - Effect of lung volume on lung resistance and elastance in awake subjects measured during sinusoidal forcing. AB - BACKGROUND: Although lung volume may be changed by certain procedures during anesthesia and mechanical ventilation, dependence of the dynamic mechanical properties of the lungs on lung volume are not clear. Based on studies in dogs, the authors hypothesized that changes in lung mechanics caused by anesthesia in healthy humans could be accounted for by immediate changes in lung volume and that lung resistance will not be decreased by positive end-expiratory airway pressure if tidal volume and respiratory frequency are in the normal ranges. METHODS: Lung resistance and dynamic lung elastance were measured in six healthy, relaxed, seated subjects during sinusoidal volume oscillations at the mouth (5 mL/kg; 0.4 Hz) delivered at mean airway pressure from -9 to +25 cmH2O. Changes in lung volume from functional residual capacity were measured with inductance plethysmographic belts. RESULTS: Decreases in mean mean airway pressure that caused decreases in lung volume from functional residual capacity comparable to those typically observed during anesthesia were associated with significant increases in both dynamic lung elastance and lung resistance. Increases in mean mean airway pressure that caused increases in lung volume from functional residual capacity did not increase lung resistance and increased dynamic lung elastance only above about 15 cmH2O. CONCLUSIONS: Increases in dynamic lung elastance and lung resistance with anesthesia can be explained by the accompanying, acute decreases in lung volume, although other factors may be involved. Increasing lung volume by increasing mean airway pressure with positive end-expiratory pressure will decrease lung resistance only if the original lung volume is low compared to awake, seated functional residual capacity. PMID- 8512102 TI - Use of ultrasound to enhance the local anesthetic effect of topically applied aqueous lidocaine. AB - BACKGROUND: Currently available local anesthetics, such as EMLA (eutectic mixture of local anesthetics), have poor skin penetration when administrated topically. As 60 min is needed for EMLA to be fully effective, attempts to accelerate transdermal delivery of a local anesthetic, such as lidocaine, by use of "electrical" and "physical" energy has previously been reported. The current experiment was undertaken to determine whether ultrasonic energy can increase the local anesthetic effect of lidocaine in the skin of mice. METHODS: Hairless mice were immersed in a beaker containing 2% aqueous lidocaine. Ultrasound (48kHz, 0.17 W/cm2) was applied to the beaker by an ultrasound-generating water tank for 5 min. To examine anesthetic effects, the skin of the legs was stimulated using various voltages ranging from 0 to 50 V before and after treatment. The number of times the hairless mouse reacted out of six stimulations was counted. RESULTS: Stimulation by 15 V at 30 min after lidocaine and ultrasound exposure resulted in positive reaction of 1.3 +/- 1.6 (mean +/- SD) compared with 5.2 +/- 2.0 before treatment. Significant anesthetic effects continued for 2 h. Immersion to lidocaine alone without ultrasound showed no evidence of analgesia after treatment. Ultrasound alone to the legs also caused no anesthetic effects. CONCLUSIONS: It was concluded that ultrasound exposure to the legs of hairless mice along with topical 2% lidocaine solution rapidly induced an anesthetic effect. PMID- 8512103 TI - Comparison of low concentrations of halothane and isoflurane as bronchodilators. AB - BACKGROUND: Although high concentrations of all currently used inhalational anesthetics are thought to be good bronchodilators, studies using traditional measures of airway tone fail to show differences in airway responsiveness during halothane, enflurane, and isoflurane use. Using a more sensitive technique, the authors compared the ability of halothane and isoflurane to dilate histamine constricted airways at equivalent MAC concentrations. METHODS: Responses of histamine-constricted individual airways to increasing doses of halothane and isoflurane were directly measured using high-resolution computed tomography (HRCT). Fifteen studies were performed in five dogs. All dogs were initially anesthetized with thiopental 15 mg/kg followed by a 10-mg.kg-1 x h-1 maintenance dose. Following tracheal intubation, the lungs were mechanically ventilated (15 ml/kg, 15 bpm). The airways were constricted with intravenous histamine 200 micrograms/min. On alternate days, the dogs subsequently received increasing concentrations of either halothane or isoflurane (0.6, 1.1, and 1.7 MAC). On a separate day, the dogs received atropine 0.2 mg/kg after the histamine infusion and the study was repeated. RESULTS: Histamine decreased airway area 34 +/- 2.5% (mean +/- SEM). All preconstricted airways showed a significant dose-dependent dilation to halothane and isoflurane at concentrations of 0.6, 1.1, and 1.7 MAC. Halothane significantly dilated airways to a greater extent than isoflurane at 0.6 and 1.1 MAC (P < 0.001). This effect was most pronounced in airways less than 3 mm in diameter. At 1.7 MAC, there was no significant difference between the two agents (P = 0.42). Atropine (0.2 mg/kg) reversed the airway constriction elicited by intravenous histamine. The histamine-preconstricted airways area increased 370 +/- 34% (P < 0.0001) after atropine. CONCLUSIONS: Halothane and isoflurane dilate histamine-constricted airways in a dose-dependent manner. However, at low concentrations, halothane was a more effective bronchodilator than isoflurane at equivalent MAC doses. PMID- 8512104 TI - Effects of nifedipine with isoflurane, halothane, or enflurane on automaticity, conduction, and contractility in isolated guinea pig hearts. AB - BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both groups of drugs appear to exert both qualitatively and quantitatively different effects on electrophysiologic and mechanical function. The aim of this study was to compare the direct cardiac effects of the calcium channel blocker nifedipine in the absence and presence of isoflurane, halothane, or enflurane. METHODS: Guinea pig hearts (N = 36) were isolated and perfused with oxygenated Krebs-Ringer solution (pH 7.4, 37 degrees C). Recording electrodes were placed in the right atrium and ventricle to measure heart rate and atrioventricular (AV) conduction time. Isovolumetric left ventricular pressure (LVP) was measured via a latex balloon and transducer. Hearts were randomly assigned to one of three anesthetic groups at 0.7 and 1.4 minimum alveolar concentration (MAC) and treated with 15 and 30 nM nifedipine. RESULTS: Nifedipine alone significantly decreased atrial rate and left ventricular pressure, without prolonging AV conduction. Nifedipine plus isoflurane, halothane, or enflurane did not significantly prolong AV conduction compared with the respective anesthetic agent alone, but nifedipine plus isoflurane, halothane, or enflurane significantly decreased atrial rate compared with the effect of the anesthetic alone. Halothane or enflurane plus nifedipine significantly decreased atrial rate more than nifedipine alone or isoflurane plus nifedipine. Isoflurane, halothane, or enflurane plus nifedipine significantly depressed LVP more than the respective anesthetic agent alone. Halothane or enflurane plus nifedipine also significantly depressed LVP more than isoflurane plus nifedipine or nifedipine alone. CONCLUSIONS: This study demonstrates that the combined treatment of nifedipine and volatile anesthetics, especially enflurane, additively depresses atrial rate and contractility, but not AV conduction in vitro. In comparison with results reported previously, these effects appear less pronounced than those of the combination of volatile agents with diltiazem and, especially, verapamil. PMID- 8512105 TI - Flux of morphine, fentanyl, and alfentanil through rabbit arteries in vivo. Evidence supporting a vascular route for redistribution of opioids between the epidural space and the spinal cord. AB - BACKGROUND: It has been suggested that opioids may move from the epidural space to the spinal cord by way of the spinal radicular arteries. However, there are no data that address this proposed mechanism. The goal of the current study was to determine whether the radicular arterial supply of the spinal cord is a viable route for movement of opioids between the epidural space and spinal cord. METHODS: The carotid and femoral arteries of anesthetized rabbits were exposed, ligated distally, and cannulated proximal to the ligature. A fluid reservoir was placed around the study vessel and filled with saline buffered to pH = 7.4 or 9.0. The study drug (morphine, fentanyl, or alfentanil) and a radiolabeled tracer were added to the reservoir. Blood was collected as it flowed through the arterial segment bathed by the fluid reservoir and analyzed by scintillation counting to determine how much drug diffused through the arterial wall per minute. RESULTS: Relative flux rates through the carotid artery at pH = 7.4 were alfentanil flux > fentanyl > morphine. Increasing the pH to 9.0 resulted in a significant decrease in fentanyl's flux, but no significant change in alfentanil's or morphine's flux. In addition, the data demonstrate a biphasic relationship between octanol:buffer distribution coefficient and transarterial flux rates. CONCLUSIONS: Because the critical step in transporting drug via radicular arteries is diffusion through the radicular artery wall, these data support the idea that drugs may gain direct access to the spinal cord by diffusing into the radicular arteries as they traverse the epidural space en route to the spinal cord. PMID- 8512106 TI - Acute volume regulation of brain cells in response to hypertonic challenge. AB - BACKGROUND: Hypertonic dehydration of the brain through administration of osmotic agents, either alone or in combination with "loop" diuretics, has been a mainstay in the treatment of increased intracranial pressure for decades. Controversy exists, however, as to the mechanism and long-term value of such therapy. Although many cell types possess volume regulatory mechanisms capable of opposing hypertonic dehydration, such behavior in the brain is poorly understood. METHODS: As a model for the mammalian central nervous system, the real-time volume behavior of rat C6 glioma cells was observed by laser light scattering during hypertonic challenge. Cells were allowed to equilibrate in isotonic balanced salt solutions at physiologic pH and temperature, and then rapidly exposed to hypertonic solutions. Experiments were conducted in the presence and absence of sodium, chloride, and the loop diuretic bumetanide to assess their roles in volume regulation. RESULTS: In response to acute, large (70 mOsm) hypertonic exposures, cells immediately shrank and then rapidly regulated their volume completely back to control within minutes. In the presence of the loop diuretic bumetanide, the volume regulatory process was significantly inhibited with only 54% recovery observed at concentrations of 10(-4) M. Volume regulation was also significantly inhibited by removal of extracellular sodium and chloride. CONCLUSIONS: Brain cells possess powerful, electrolyte-dependent and bumetanide sensitive volume-regulatory mechanisms that directly oppose attempted osmotic shrinkage. These observations suggest a possible new mechanism for the clinically observed synergistic effects of loop and osmotic diuretics in reduction of brain volume. PMID- 8512107 TI - Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine. AB - BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10 day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane. PMID- 8512108 TI - Surfactant treatment of respiratory failure induced by hydrochloric acid aspiration in rats. AB - BACKGROUND: The surfactant system seems to be involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration. This study was an investigation of the effect of different treatment strategies using an exogenous surfactant preparation on lung function of rats suffering from respiratory failure after intratracheal HCl instillation. METHODS: In rats anesthetized with halothane, nitrous oxide, and oxygen, tracheotomy was performed and the lungs were mechanically ventilated. Respiratory failure was induced by intratracheal instillation of HCl (0.1 N, 3 ml/kg). After the PaO2 decreased to < 200 mmHg, the animals were randomly divided into five groups. Group I received no treatment; group II received a natural surfactant preparation intratracheally (200 mg/kg); group III underwent bronchoalveolar lavage (BAL) with saline, followed by surfactant treatment (200 mg/kg); and groups IV and V underwent BAL with saline and a diluted surfactant suspension (3.3 mg/ml in 30 ml/kg), respectively. Groups IV and V received a second and third BAL 60 and 120 min after the first lavage. Blood gas analysis and protein measurements in BAL fluids were performed. RESULTS: Gas exchange improved in Groups III and V only. Protein concentrations were high in all BAL fluids. In the rats receiving BAL three times (groups IV and V), a decrease in protein concentration was observed. CONCLUSIONS: From these results, it was concluded that plasma-derived proteins (which are known to inhibit surfactant function) are washed out of the alveoli by BAL, resulting in improved efficacy of surfactant treatment. PMID- 8512109 TI - Hypothermia eliminates isoflurane requirements at 20 degrees C. AB - BACKGROUND: Hypothermia decreases anesthetic requirements, but the temperature that completely eliminates anesthetic needs has not been previously determined. METHODS: Eight female goats were anesthetized with isoflurane and catheters were placed in the femoral artery and cranial vena cava, after which the right carotid artery and external jugular vein were dissected free. Peripheral temperature was monitored in the rectum and core temperature in the vena cava. A thermistor was placed in the epidural space via a small burr hole to monitor brain temperature. Minimum alveolar concentration (MAC) for isoflurane was determined by eliciting gross, purposeful movement with a tail clamp. Cardiopulmonary bypass (CPB) was established using bubble oxygenators with venous blood drained from a jugular vein and arterial blood infused with a roller pump into the carotid artery. The animals were cooled to approximately 29 degrees C, and MAC redetermined, after which further cooling to 20 degrees C was accomplished. Isoflurane was eliminated, core and brain temperature adjusted in 2-3 degrees C increments, and the tail clamp applied until two temperatures were found that just permitted and just prevented movement. The animals were rewarmed, isoflurane added, and post CPB MAC determined. RESULTS: At 38.5 degrees C, pre-CPB MAC was 1.3 +/- 0.1% (mean +/- SEM). At 29.0 degrees C, MAC was 0.7 +/- 0.1%, and the anesthetizing temperature was 20.1 +/- 0.6 degrees C. At 37.3 degrees C, post-CPB MAC was 1.0 +/- 0.1% (P < 0.05 vs. pre-CPB). CONCLUSIONS: These results confirm the rectilinear decrease in MAC seen in previous studies and establishes the anesthetizing temperature at 20 degrees C. PMID- 8512110 TI - Pulmonary uptake of propofol in cats. Effect of fentanyl and halothane. AB - BACKGROUND: Many drugs are removed by the lung. The pulmonary uptake of one drug can be inhibited when a second, highly accumulated drug is administered parenterally or as a chronic oral treatment. The effect of inhalational anesthetics on pulmonary drug uptake has not been extensively studied and may alter pharmacokinetics of intravenously administered drugs. METHODS: The uptake of propofol by the lung during a single passage through the pulmonary circulation was studied in four groups of anesthetized cats: spontaneously breathing cats (control group, n = 6), cats whose lungs were mechanically ventilated (n = 6), and cats whose lungs were mechanically ventilated and that were anesthetized with 1% (n = 6) or 1.5% (n = 6) halothane. In an additional group, the single-pass pulmonary uptake of propofol was studied in six spontaneously breathing cats pretreated with fentanyl. The amount of propofol taken up by the lung during the first pass was measured from double indicator-dilution outflow curves using indocyanine green (ICG) as the intravascular reference indicator. RESULTS: The first-pass uptake of propofol (mean +/- SEM) was 61.3 +/- 4.9% and 60 +/- 3.7% of the injected dose in control cats and in cats whose lungs were mechanically ventilated, respectively. Although exposure of the animals to 1% halothane had no significant effect on pulmonary extraction of propofol, the first-pass uptake decreased significantly to 38.8 +/- 6.9% in cats exposed to 1.5% halothane compared with control cats and to cats undergoing mechanical ventilation of the lungs without exposure to halothane. Also, in animals pretreated with fentanyl, propofol uptake was reduced to 40 +/- 5% compared with the control group. CONCLUSIONS: The results demonstrate a substantial extraction of propofol by the lung that is not affected by mechanical ventilation. Inhibition of propofol uptake by 1.5% halothane and by fentanyl provides a potential mechanism of drug drug interaction that may interfere with the pharmacokinetic profile of propofol, and may alter the amount of propofol needed to achieve or supplement a given depth of anesthesia. PMID- 8512111 TI - Amrinone and the pulmonary vascular pressure-flow relationship in conscious control dogs and following left lung autotransplantation. AB - BACKGROUND: Amrinone, a bipyridine compound, is known to improve left ventricular function via its positive inotropic and afterload-reducing effects. The goal of this study was to assess the efficacy of amrinone as a pulmonary vasodilator, an effect that could be beneficial in the setting of right heart failure associated with pulmonary hypertension. METHODS: Investigated were the effects of intravenous amrinone (750 micrograms/kg loading dose plus 1-20 micrograms.kg 1.min-1 maintenance dose) on the left pulmonary vascular pressure-flow (LPQ) relationship in chronically instrumented, conscious dogs. The effects of amrinone on the LPQ relationship were assessed in a series of conscious control dogs with (n = 10) and without (n = 9) acute preconstriction with the thromboxane analog U46619 and in a series of conscious dogs 2-4 weeks after left lung autotransplantation (LLA) with (n = 8) and without (n = 8) acute U46619 preconstriction. Left pulmonary vascular pressure-flow plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure/left atrial pressure [PAP/LAP]) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right pulmonary artery. RESULTS: Amrinone had no effect on the baseline LPQ relationship in control dogs. U46619 caused acute pulmonary vasoconstriction. For example, PAP/LAP at left pulmonary blood flow of 70 ml.min 1.kg-1 was increased (P < 0.01) from 16 +/- 2 to 37 +/- 2 mmHg during U46619 administration. In this setting of acute preconstriction, amrinone caused pulmonary vasodilation, i.e., PAP/LAP was decreased (P < 0.05) from 37 +/- 2 to 32 +/- 2 mmHg. Left lung autotransplantation was associated with a marked shift in the LPQ relationship, indicating a chronic increase in pulmonary vascular resistance, i.e., PAP/LAP was increased (P < 0.01) from 15 +/- 2 to 32 +/- 3 mmHg. Despite the chronic increase in pulmonary vascular resistance after LLA, amrinone had no effect on the baseline LPQ relationship. However, after acute preconstriction with U46619 after LLA, amrinone caused pulmonary vasodilation, i.e., PAP/LAP was decreased (P < 0.05) from 45 +/- 4 to 39 +/- 4 mmHg. CONCLUSIONS: These results indicate that amrinone exerts a significant, although relatively modest pulmonary vasodilator influence in the setting of acute pulmonary vasoconstriction in conscious control dogs and in conscious dogs after LLA. However, amrinone did not reverse the chronic increase in pulmonary vascular resistance associated with LLA. PMID- 8512112 TI - Contamination of anesthetic vaporizer contents. PMID- 8512113 TI - Deliberate hypoventilation in a patient with air trapping during lung transplantation. PMID- 8512114 TI - Prolonged neuromuscular block following mivacurium. PMID- 8512115 TI - Cervical epidural block can relieve postoperative intractable hiccups. PMID- 8512117 TI - Epidural hematoma associated with epidural anesthesia: complications of anticoagulant therapy. PMID- 8512116 TI - Concentration ranges in dose-response determinations for propofol and thiopental in vitro. PMID- 8512118 TI - A simple alternative precordial stethoscope. PMID- 8512119 TI - Subanesthetic isoflurane and the ventilatory response to hypoxemia. PMID- 8512120 TI - A right-angled alligator clip for use with insulated nerve block needles. PMID- 8512121 TI - Parents in the operating room? PMID- 8512122 TI - A new transparent disposable plastic face mask for children and adults. PMID- 8512123 TI - An unusual cause of an erroneous noninvasive blood pressure reading. PMID- 8512124 TI - The laryngeal mask airway as an aid to intubation in patients at risk of aspiration? PMID- 8512125 TI - Clinton honors nurses at Rose Garden ceremony. PMID- 8512126 TI - ANA: making health care reform work for all nurses. PMID- 8512127 TI - Respondents ask First Lady to rely on nurses' expertise. PMID- 8512128 TI - Survey findings show nurses want to play a larger role in the reformed health care system. PMID- 8512129 TI - Capitol Hill legislative briefing highlights primary health care nursing models. PMID- 8512130 TI - Taking action against violence in the workplace. PMID- 8512132 TI - Help wanter: nurses across America. PMID- 8512131 TI - Study shows that many nurses fear contracting AIDS. PMID- 8512133 TI - A grassroots network--taking ANA's legislative agenda to the front lines. PMID- 8512134 TI - ANA endorses AHCPR guidelines for detection, treatment of depression. PMID- 8512135 TI - Public health stands as a proven models for future delivery systems. PMID- 8512136 TI - Opening doors for advanced practice opportunities. PMID- 8512137 TI - Future mental health needs of Americans could be served by CNSs. PMID- 8512138 TI - Gains and challenges in prescriptive authority. PMID- 8512139 TI - ANA to task force: consider reform's impact on nurses. PMID- 8512140 TI - Opportunities in the managed care industry. PMID- 8512141 TI - A day in the life of a nurse. NP uses holistic approach on college campus. PMID- 8512142 TI - Operation immunize: Kansas' success due to nurses. PMID- 8512143 TI - Outreach is key to success of Pa. immunization program. PMID- 8512144 TI - RN layoffs of growing concern to ANA. PMID- 8512145 TI - Mountain states need nursing faculty. PMID- 8512146 TI - Reform issues affect Midwest recruiting. PMID- 8512147 TI - Health care reform: a view from the bottom. PMID- 8512148 TI - Bringing nursing's vision to the White House. PMID- 8512149 TI - Controlling costs, broadening access. PMID- 8512150 TI - Articulating nursing's unique contributions. PMID- 8512151 TI - Higher education: preparing the post-reform nurse. PMID- 8512152 TI - Clinton tells nurses that health care, economy, deficit must be addressed simultaneously. PMID- 8512153 TI - Sickle cell guidelines stress screening. PMID- 8512154 TI - Facial expression and emotion. AB - Cross-cultural research on facial expression and the developments of methods to measure facial expression are briefly summarized. What has been learned about emotion from this work on the face is then elucidated. Four questions about facial expression and emotion are discussed: What information does an expression typically convey? Can there be emotion without facial expression? Can there be a facial expression of emotion without emotion? How do individuals differ in their facial expressions of emotion? PMID- 8512155 TI - Behavior analysis applications and interdisciplinary research strategies. AB - The emergence of behavioral pharmacology as a basic and applied science owes its origin and development to the interactive methodological-conceptual advances that have characterized interdisciplinary research initiatives over the past half century. The resulting enhancement of academic training and research opportunities has broadened the application of behavior analysis principles to a range of clinical, educational, and industrial settings. The extent of this applied behavioral science outreach is unconstrained even by the challenges of inhospitable terrestial and extraterrestial environments. PMID- 8512156 TI - Violence and U.S. regional culture. AB - The U.S. South, and western regions of the U.S. initially settled by Southerners, are more violent than the rest of the country. Homicide rates for White Southern males are substantially higher than those for White Northern males, especially in rural areas. But only for argument-related homicides are Southern rates higher. Southerners do not endorse violence more than do Northerners when survey questions are expressed in general terms, but they are more inclined to endorse violence for protection and in response to insults. Southern subjects responded with more apparent anger to insults than did Northerners and were more likely to propose violent solutions to conflicts presented in scenarios after being insulted. The social matrix that produced this pattern may be the culture of honor characteristic of particular economic circumstances, including the herding society of the early South. Consistent with this possibility, the herding regions of the South are still the most violent. PMID- 8512157 TI - Reflections of a 40-year exploration. A scientific view on homosexuality. PMID- 8512158 TI - Establishing a therapeutic range for heparin therapy. AB - OBJECTIVE: To compare two methods of determining a therapeutic range of activated partial thromboplastin time (aPTT) results. DESIGN: Cohort studies. SETTING: Referral teaching hospital. PATIENTS: Inpatients who received unfractionated heparin intravenously for venous thromboembolic disease. MEASUREMENTS: A therapeutic range determined by aPTT ratios of 1.5 to 2.5 times the control value as compared with a therapeutic range determined by protamine titration heparin levels of 0.2 to 0.4 U/mL. RESULTS: For all aPTT reagents studied, a ratio of 1.5 times the control value is much less than a minimum protamine titration heparin level of 0.2 U/mL. Various manufacturers' aPTT reagents and reagent lots from the same manufacturer show considerable variation in response to heparin and therefore have different therapeutic ranges. CONCLUSIONS: A different dose of heparin would be required to produce an aPTT ratio of 1.5 times the control value, depending on the reagent used. Establishing a therapeutic range for aPTT results using protamine titration heparin levels of 0.2 to 0.4 U/mL as a reference standard is practical and compensates for the variable response of aPTT reagents to heparin. PMID- 8512159 TI - Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. AB - OBJECTIVE: To determine the long-term course of non-A, non-B post-transfusion hepatitis. DESIGN: Follow-up in 1989 to 1992 of patients prospectively identified as having contracted non-A, non-B post-transfusion hepatitis between 1972 and 1980. SETTING: A university hospital. PATIENTS: Patients who were prospectively followed from receipt of blood products and in whom otherwise unexplained abnormalities in their serum alanine aminotransferase levels developed without serologic evidence of exposure to hepatitis A or B. MEASUREMENTS: The presence or absence of clinical evidence of liver failure or symptoms of chronic hepatitis. RESULTS: Of 90 patients identified in the 1970s, 80 were recontacted and evaluated between 1989 and 1992. Based on the current status of these 80 patients and on the last known status of the remaining patients, the following observations were made: 1) Although about 40% had some symptoms during the early phase of the disease, none subsequently experienced significant clinical problems related to hepatic inflammation; 2) eight patients (seven with chronic hepatitis) developed hepatic failure; and 3) life-table analysis showed that the probabilities of developing clinical evidence of cirrhosis after 16 years of disease in the entire cohort, in the subgroup who developed chronic hepatitis, in the patients who had hepatitis C, and in those with chronic hepatitis C were 18%, 21%, 17%, and 20%, respectively. CONCLUSIONS: For most of the study patients, non A, non-B post-transfusion hepatitis was a biochemical and histologic disease that had not yet caused hepatic symptoms. If hepatic failure does occur, it is usually seen only after 10 or more years of disease. Before that time, many infected persons die due to other disease processes. PMID- 8512160 TI - Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history. AB - OBJECTIVE: To evaluate the incidence and symptoms of and risk factors for biliary sludge and gallstones during pregnancy and to assess the natural history of these conditions in the first year after delivery. DESIGN: Cohort study. PATIENTS: A total of 272 pregnant women recruited in the first trimester. MEASUREMENTS: Biliary sludge and gallstones were diagnosed using ultrasonography, both during pregnancy and after delivery. Predictors of the presence or disappearance of sludge and stones were examined. MAIN RESULTS: Overall, from the first trimester of pregnancy until the immediate postpartum period, 67 women were newly diagnosed with biliary sludge, and 6 women were newly diagnosed with gallstones. The respective incidence rates were 31% (95% Cl, 25% to 37%) and 2% (95% Cl, 0.2% to 4%). During pregnancy, 28% of women experienced biliary pain, which was associated only with presence of stones. After delivery, 92 women had sludge and 23 had stones. Sludge disappeared in 61% of these women (Cl, 50% to 73%) after a mean follow-up of 5 months, and stones disappeared in 28% of women (Cl, 10% to 46%) after 9.7 months of follow-up. CONCLUSIONS: Biliary sludge occurred frequently during pregnancy but was generally asymptomatic and often disappeared spontaneously after delivery. Gallstones were much less frequent and were more likely to be associated with biliary pain. PMID- 8512161 TI - Chronic diarrhea and malabsorption associated with enteropathogenic bacterial infection in a patient with AIDS. PMID- 8512162 TI - The periodic health examination provided to asymptomatic older women: an assessment using standardized patients. AB - OBJECTIVES: To describe physical examination and cancer prevention services provided by primary care physicians in response to the request for a "checkup" by an asymptomatic 55-year-old woman seeking to establish ongoing care; to assess the effects of two interventions (education and office organization) intended to improve these services; and to assess the feasibility of using "standardized" patients to evaluate physician responses to such a request. SETTING: Northern New England. PARTICIPANTS: Fifty-nine primary care physicians who were accepting new patients and were participating in a study of early detection and prevention of cancer. DESIGN: Cross sectional; observations of patient visits. INTERVENTIONS: Actresses trained to portray a specific patient role ("standardized" or "simulated" patients) visited each physician once. Physicians were blinded to the simulated patients' true identities. MEASUREMENTS: Actresses reported the components of the general physical examination and the cancer-related "checkup." Most interactions were audiotaped. RESULTS: Fourteen physical examination components were measured, ranging from assessment of vibratory sense (5%) to measurement of blood pressure (98%). Provision of 10 services recommended by the National Cancer Institute to standardized patients included 16% being advised to reduce dietary fat; 53% to do monthly breast self-examination; 74% to quit smoking; and 89% to obtain a mammogram. Physicians spent from 5 to 60 minutes with the patients. Two physicians did not charge, whereas others charged from $24 to $108. Study group assignment was not associated with statistical differences in provider performance. Two standardized patients (3%) were detected by physicians. Audiotapes were used to verify the actresses' ability to replicate their scenario (consistently repeat their performance) and to verify physician performance. CONCLUSIONS: Physician responses to an identical patient request varied widely in terms of time spent with the patient, the services provided, and the cost of the visit. Using standardized patients is a feasible method for assessing physician performance of the periodic health examination while controlling for case mix. PMID- 8512163 TI - Internal medicine and the journey to medical generalism. AB - The overspecialized U.S. physician workforce and mix of graduating residents undermine strategies to provide quality and affordable health care to all Americans. Several respected advisory bodies have recently proposed fundamental changes in federal policy to better match physician supply and specialty mix with health care needs. They recommend that Congress limit the total number of filled first-year resident positions to 110% of the number of U.S. medical school graduates, a 20% reduction from current levels. They have proposed that positions and funding be allocated to medical schools, teaching hospitals, residency programs, or consortia of such entities to ensure that at least 50% of each graduating residency class enters generalist practice. An all-payer, graduate medical education pool and financing system have been suggested as ways to uncouple the physician workforce from hospital service needs and to eliminate disincentives toward ambulatory and primary care training. Increases in generalist production must be accompanied by decreases in nonprimary care specialty and subspecialty positions. In addition, generalist physicians must be better prepared in managed care competencies. Given today's subspecialist surplus, managed care organizations are considering how to retrain subspecialists as generalists. The Federated Council of Internal Medicine's goal that 50% of its graduates become general internists is an important step because internists compose one sixth of all physicians and one third of all first-year residents. This article identifies the challenges that lay ahead on the road to medical generalism and what it may take to get there. PMID- 8512164 TI - The future of generalism. PMID- 8512165 TI - The other side of tomorrow. PMID- 8512166 TI - Multiple chemical sensitivities. PMID- 8512167 TI - General internists and subspecialists. PMID- 8512168 TI - Alphabet now complete. NIH discovers hepatitis Z virus. PMID- 8512169 TI - Treatment of myxedema-associated cardiogenic shock. PMID- 8512170 TI - Treatment of myxedema-associated cardiogenic shock. PMID- 8512171 TI - Management of the severely anemic Jehovah's Witness. PMID- 8512172 TI - Management of the severely anemic Jehovah's Witness. PMID- 8512174 TI - Patients' choices and the medical commons. PMID- 8512173 TI - Patients' choices and the medical commons. PMID- 8512175 TI - Paying for kidney donors. PMID- 8512176 TI - Immunoradiometric assays may miss high prolactin levels. PMID- 8512177 TI - Altered calcium signaling and neuronal injury: stroke and Alzheimer's disease as examples. AB - Several cellular signaling systems have been implicated in the neuronal death that occurs both in development ("natural" cell death) or in pathological conditions such as stroke and Alzheimer's disease (AD). Here we consider the possibility that neuronal degeneration in an array of disorders including stroke and AD arises from one or more alterations in calcium-regulating systems that result in a loss of cellular calcium homeostasis. A long-standing hypothesis of neuronal injury, the excitatory amino acid (EAA) hypothesis, is revisited in light of new supportive data concerning the roles of EAAs in stroke and the neurofibrillary degeneration in AD. Two quite new concepts concerning mechanisms of neuronal injury and death are presented, namely: 1) growth factors normally "stabilize" intracellular free calcium levels ([Ca2+]i) and protect neurons against ischemic/excitotoxic injury, and 2) aberrant processing of beta-amyloid precursor protein (APP) can cause neurodegeneration by impairing a neuroprotective function of secreted forms of APP (APPs) which normally regulate [Ca2+]i. Altered APP processing also results in the accumulation of beta-amyloid peptide which contributes to neuronal damage by destabilizing calcium homeostasis; in AD beta-amyloid peptide may render neurons vulnerable to excitotoxic conditions that accrue with increasing age (e.g., altered glucose metabolism, ischemia). Growth factors may normally protect neurons against the potentially damaging effects of calcium influx resulting from energy deprivation and overexcitation. For example, bFGF, NGF and IGFs can protect neurons from several brain regions against excitotoxic/ischemic insults. Growth factors apparently stabilize [Ca2+]i by several means including: a reduction in calcium influx; enhanced calcium extrusion or buffering; and maintenance or improvement of mitochondrial function. For example, bFGF can suppress the expression of a N methyl-D-aspartate (NMDA) receptor protein that mediates excitotoxic damage in hippocampal neurons. Growth factors may also prevent the loss of neuronal calcium homeostasis and the increased vulnerability to neuronal injury caused by beta amyloid peptide. Since elevated [Ca2+]i can elicit cytoskeletal alterations similar to those seen in AD neurofibrillary tangles, we propose that neuronal damage in AD results from a loss of calcium homeostasis. The data indicate that a variety of alterations in [Ca2+]i regulation may contribute to the neuronal damage in stroke and AD, and suggest possible means of preventing neuronal damage in these disorders. PMID- 8512178 TI - Markers of Neuronal Injury and Degeneration. Bethesda, Maryland, April 22-24, 1992. Proceedings. PMID- 8512179 TI - Mechanisms of phospholipase A2 activation and neuronal injury. PMID- 8512181 TI - Synthesis of heat shock/stress proteins during cellular injury. AB - Several conclusions can be drawn from available data on the expression of stress proteins in brain with respect to their utility as markers of cellular injury. First, it is evident that all cell types in brain are capable of expressing stress proteins, although there is striking specificity in the population responding to a given insult. The apparent hierarchy of responsiveness indicated by hsp72 expression correlates well with the relative vulnerability of specific cell populations in a given model. With increasing severity of injury there can be an attenuation of the translational component of the stress response, in that hsp72 immunoreactivity fails to accumulate even though its mRNA is abundantly expressed. For this reason, hsp72 immunoreactivity provides an index of cell populations that have responded to an insult with a functional stress response. Such a response is not sufficient to guarantee survival, since many CA1 neurons that show significant hsp72 staining are eventually lost after global ischemia in the rat. However, brief insults that result in expression of hsp72 and other proteins encoded by induced mRNAs do result in tolerance to subsequent insults. Future studies may be expected to reveal the contributions of specific gene products to the tolerant state. Meanwhile, complementary evaluations of hsp72 mRNA and protein expression provide practical means of identifying cell populations responding to diverse injuries. PMID- 8512180 TI - Neurotrophic factor deprivation-induced death. AB - Deprivation of sympathetic neurons of their physiological neurotrophic factor, nerve growth factor (NGF), leads to degeneration of soma and neurites, followed by loss of viability. The progression of degeneration and death are dependent upon macromolecular synthesis indicating an active participation of neuronal metabolism. Loss of viability begins only after a considerable delay after onset of NGF deprivation suggesting the presence of a sequence of degenerative events that triggers death. Such a sequence of degenerative events predicts that the activity of neuroprotective agents functioning by different mechanisms will be restricted to particular windows in time. The time-course of commitment to die as measured by the ability of NGF-deprived neurons to respond to NGF with long-term survival precedes the time-course of loss of viability by only a few hours, demonstrating that NGF displays neuroprotective properties for most of the time between onset of deprivation and death. Furthermore, NGF repairs and reverses the degenerative changes caused by prolonged periods of NGF deprivation. Because of these two aspects of NGF action, NGF demonstrates superior properties as a neuroprotective agents. NGF deprivation initiates DNA fragmentation of the neuronal genome into oligonucleosomal fragments in close temporal association with the onset of commitment to die. This is consistent with the idea that DNA fragmentation may be instrumental in causing the commitment to die. Thus, DNA fragmentation may serve as a marker of the physiologically most relevant critical step occurring during degeneration and may indicate the end of the period during which trophic factors are useful as neuroprotective agents. These results may be transferable to neurodegenerative diseases or sequelae of neuronal injury because of similarities in the phenomenology of degeneration and death. PMID- 8512182 TI - Molecular mechanisms of selective neurotoxicants: studies on organotin compounds. PMID- 8512183 TI - Quantitative features of reactive gliosis following toxicant-induced damage of the CNS. PMID- 8512184 TI - Quinolinic acid and inflammation. PMID- 8512185 TI - Release of membrane-associated growth factors during neural injury. AB - The release of membrane-associated growth factors after neural injury may influence the outcome of the recovery. For example, for remyelination to occur after neural injury it is critical for the glial cell to proliferate prior to remyelination in both the PNS and CNS. In the CNS, the relative response of the oligodendrocytes and astroglia to growth factors mobilized during neural injury may play a role in the cellular dynamics of repair of neural injury or scarring and subsequent failure to repair neural injury. In support of this view, we have studied the mitotic potential and cell cycle kinetics of cultured adult oligodendrocytes and found that these adult cells respond only weakly to factors such as FGF which are known to be potent mitogens for neonatal cells. However, given the same dose of FGF, adult astrocytes are mitotically stimulated to a much greater degree than are the adult oligodendrocytes (Vick and De Vries, unpublished observations). Given the pathways which may be operative in the release of growth factors after injury, it has not escaped our attention that, provided the released factors are in equilibrium with easily accessible and peripheral body fluids, these released factors may serve as new markers for neural injury. Further experiments are in progress to explore this possibility. PMID- 8512186 TI - Sulfated glycoprotein-2: an emerging molecular marker for neurodegeneration. PMID- 8512187 TI - Laminin-like and laminin-binding protein-like immunoreactive astrocytes in rat hippocampus after transient ischemia. Antibody to laminin-binding protein is a sensitive marker of neural injury and degeneration. PMID- 8512188 TI - Use of neurite outgrowth as an in vitro method of assessing neurotoxicity. AB - This work shows that the neurotoxic excitatory amino acids beta-N-methylamino alanine, BMAA, and kainate, modulate neurite outgrowth; this was assessed by measuring the levels of two separate neurofilament proteins (68 kD and 160 kD), in a mouse neuroblastoma cell line, (NB41A3). BMAA has been proposed to be the exogenous excitotoxin in Guam disease or amyotrophic lateral sclerosis (ALS/parkinsonian/dementia; Guam ALS-PD). Kainate is a glutamate analogue which causes excitotoxic damage associated with excessive entry of calcium into neurons. The results show that at low doses (10(-9) to 10(-7) M) both BMAA and kainate decrease the concentration of the two neurofilament proteins. However at high doses (10(-6) to 10(-5) M) they cause an apparent accumulation of the neurofilament proteins; the effect is more marked with BMAA. These results support the continued development of an in vitro test for neurotoxicity based on neurite outgrowth. PMID- 8512189 TI - Preliminary observations on the in vitro toxicity of N-butylbenzenesulfonamide: a newly discovered neurotoxin. PMID- 8512190 TI - Heat shock proteins used to show that haloperidol prevents neuronal injury produced by ketamine, MK801, and phencyclidine. PMID- 8512191 TI - The effects of intraseptal brain-derived neurotrophic factor on cognition in rats with MS/DB lesions. PMID- 8512192 TI - Developmental differences in neural damage following trimethyl-tin as demonstrated with GFAP immunohistochemistry. AB - Long-Evans rat pups received intraperitoneal (i.p.) injections of trimethyl-tin (TMT) 6 mg/kg hydroxide or saline on postnatal day (PND) 10 or PND 18 and were sacrificed for immunohistochemical staining for glial fibrillary acidic protein (GFAP) on PND 12, 18, 20, or 25. After dosing with TMT on PND 10 there was a transient increase in GFAP immunoreactivity (IR) in the amygdala, piriform, and entorhinal cortex 2 days post-dosing (PND 12) and a persistent increase in GFAP IR in the hippocampus and cingulate cortex up to two weeks post-dosing. Following dosing with TMT on PND 18 there was a delayed (PND 25) increase in GFAP IR in the amygdala, hippocampus, cingulate, piriform, and entorhinal cortex. In addition, increases in GFAP IR were observed in the neocortex 7 days post-dosing, which was not observed following earlier postnatal dosing. The regions in which gliosis and loss of Nissl-staining were consistent for the different time points of TMT treatment were the amygdala, hippocampus, cingulate, piriform, and entorhinal cortex. The present findings indicate the GFAP immunohistochemistry can be used to reveal regional effects of developmental neurotoxicant exposure during early stages of development. PMID- 8512193 TI - The goldfish as a drug discovery vehicle for Parkinson's disease and other neurodegenerative disorders. PMID- 8512194 TI - Calpain activity in organophosphorus-induced delayed neuropathy (OPIDN): effects of a phenylalkylamine calcium channel blocker. PMID- 8512195 TI - Detection of early axonal degeneration in the mammalian central nervous system by magnetization transfer techniques in magnetic resonance imaging. PMID- 8512196 TI - Examination of the role of calcium in neuronal death. PMID- 8512197 TI - Elevation of nerve growth factor receptor-truncated in the urine of patients with diabetic neuropathy. PMID- 8512198 TI - Oxidative damage in double-stranded genomic DNA as measured by GC/MS assay of a thymine glycol derivative. PMID- 8512199 TI - Free radical and lipid peroxidation in manganese-induced neuronal cell injury. PMID- 8512200 TI - Glutathione disulfide (GSSG) as a marker of oxidative injury to brain mitochondria. PMID- 8512201 TI - Manganese transport and Na/K/Cl cotransport in PC-12 cells. PMID- 8512202 TI - The neuronal cytoskeleton in disorders of late onset and slow progression. PMID- 8512203 TI - Long-term changes in glial fibrillary acidic protein and calcium levels in rat hippocampus after a single systemic dose of kainic acid. PMID- 8512204 TI - Glial fibrillary acidic protein (GFAP) indicates in vivo exposure to environmental contaminants: PCBs in the Atlantic tomcod. PMID- 8512205 TI - Growth-associated protein-43 (GAP-43) is expressed by glial cells of the central and peripheral nervous system. PMID- 8512206 TI - The expression of B-50/GAP-43 in Schwann cells. PMID- 8512208 TI - Cellular responses of identified lamprey central neurons to axonal and dendritic injury. An in situ model for studying cellular injury on the single cell level in the vertebrate CNS. PMID- 8512207 TI - Gene expression in brain injury: identification of a new cDNA structurally related to adhesive and trophic agents. PMID- 8512209 TI - Spectrin proteolysis in the hippocampus: a biochemical marker for neuronal injury and neuroprotection. PMID- 8512210 TI - The lysosomal system in neuronal cell death: a review. AB - The lysosomal system has often been considered a prominent morphologic marker of distressed or dying neurons. Lysosomes or their constituent hydrolases have been viewed in different neuropathologic states as either initiators and direct agents of cell death, agents of cellular repair and recompensation, effectors of end stage cellular dissolution, or autolytic scavengers of cellular debris. Limited data and limitations of methodology often do not allow these potential roles to be discriminated. In all forms of neurodegeneration, it may be presumed that lysosomes ultimately rupture and release various hydrolases that promote cell autolysis during the final stages of cellular disintegration. Beyond this perhaps universal contribution to cell death, the degree to which the lysosomal system may be involved in neurodegenerative states varies considerably. In many conditions, morphologic evidence for activation of the lysosomal system is minimal or undetectable. In other cases, lysosomal activation is evident only when other morphologic signs of cell injury are also present. This level of participation may be viewed as either an attempt by the neuron to compensate for or repair the injury or a late-stage event leading to cell dissolution. The early involvement of the lysosomal system in neurodegeneration occurs most commonly in the form of intraneuronal accumulations of abnormal storage profiles or residual bodies (tertiary lysosomes). Very often the lysosomal involvement can be traced to a primary defect or dysfunction of lysosomal components or to accelerated or abnormal membrane breakdown that leads to the buildup of modified digestion resistant substrates within lysosomes. Because they are often striking, changes in the lysosomal system are a sensitive morphologic indicator of certain types of metabolic distress; however, whether they reflect a salutary response of a compromised neuron or a mechanism to promote cell death and removal of debris from the brain remains to be established for most conditions. Factors that may influence the lysosomal response during lethal neuronal injury include species differences, stage of neuronal development, duration of injury and pace of cell death. The lysosomal system may be more closely coupled to certain forms of neuronal cell death in lower vertebrate or invertebrate systems than in mammalian systems. PMID- 8512211 TI - The discovery of the melanotropins. A history of pituitary endocrinology. PMID- 8512212 TI - Structure and regulation of the melanin-concentrating hormone gene. PMID- 8512213 TI - Control of melanotrope cell activity in Xenopus laevis. PMID- 8512214 TI - Mammalian paired basic amino acid convertases of prohormones and proproteins. PMID- 8512216 TI - Multihormonal regulation of pituitary melanotrophs. PMID- 8512215 TI - Peptidylglycine alpha-amidating monooxygenase and other processing enzymes in the neurointermediate pituitary. AB - Studies on the mRNAs encoding PAM and on the various PAM proteins have begun to reveal some of the intricate mechanisms used to optimize the ability of this enzyme to carry out the alpha-amidation of peptides. Comparison of the regulatory elements governing expression of the various enzymes involved in peptide processing should reveal common elements. Knowledge of the processing enzymes themselves should help us to understand how these enzymes function in the secretory granule environment. In addition to their catalytic domains, other processing enzymes, like PAM, may well have processing domains and routing domains designed to optimize their ability to function in secretory granules. PMID- 8512217 TI - Analysis of inositol phosphate metabolism in melanotrope cells of Xenopus laevis in relation to background adaptation. AB - The present study examined inositol phosphate metabolism in melanotrope cells of Xenopus laevis to determine if inositol phosphates are involved in regulating the biosynthetic or secretory activity of these cells. No correlation could be found between inositol phosphate metabolism and the secretory activity of the melanotrope cells. Therefore, we conclude that inositol phosphate production is not directly involved in the regulation of release of alpha-MSH from these cells. However, there were dramatic differences in the capacity of the melanotrope cells to produce inositol phosphates dependent on the state of background adaptation of the animals from which the melanotropes were derived; cells from white-adapted animals had a low capacity to produce inositol phosphates, whereas melanotropes from black-adapted animals had a high capacity in this regard. During adaptation of animals from a white to a black background, the capacity of the melanotrope cells to produce inositol phosphates was only very slowly acquired, reminiscent of the slow acquisition displayed by these cells to produce POMC during background adaptations. Likewise, during black to white background adaptation, the melanotrope cells very slowly lost the capacity to phosphorylate inositol, which correlates with the slow loss of the biosynthetic capacity of melanotrope cells during such adaptations. Altogether we conclude that inositol phospholipid metabolism is likely involved in the regulation of the biosynthetic processes of melanotrope cells of Xenopus laevis. PMID- 8512218 TI - Calcium signals in melanotrophs and their relation to autonomous secretion and its modification by inhibitory and stimulatory ligands. PMID- 8512219 TI - Regulation of proopiomelanocortin gene expression in rat brain and pituitary as studied by in situ hybridization. AB - The major sites of POMC gene expression are the intermediate and anterior lobes of the pituitary and the arcuate nucleus of the hypothalamus. We have investigated the regulation of POMC mRNA levels in the pituitary and hypothalamus by quantitative in situ hybridization using a 35S-labeled cDNA probe encoding or POMC. In the arcuate nucleus, where the POMC-producing neurons are concentrated, adrenalectomy induced a marked decrease in POMC mRNA levels, an effect that was completely reversed by dexamethasone administration. The stimulating effect of dexamethasone was much more striking in the most caudal regions of the nucleus. Since in the anterior pituitary, glucocorticoids exert an inhibitory action on POMC gene expression, it might be suggested that POMC is differentially regulated by glucocorticoids in the anterior pituitary and the hypothalamus. Ovariectomy induced an increase in mRNA levels in the most rostral region of the arcuate nucleus, an effect that was prevented by the concurrent administration of estradiol or dihydrotestosterone. The role of dopamine was investigated following the administration of the dopaminergic antagonist haloperidol and the D2 dopaminergic receptor agonist bromocriptine. In the arcuate nucleus, bromocriptine increased and haloperidol decreased the hybridization signal. Conversely, in the intermediate lobe of the pituitary, bromocriptine markedly depressed and haloperidol increased the levels of mRNA. These results indicate that the population of POMC neurons in the arcuate nucleus is heterogeneous. They also demonstrate that POMC gene expression is regulated by central and peripheral factors and that this regulation is different in the brain and the pituitary. PMID- 8512220 TI - Hormonal regulation of melanogenesis in mouse melanoma and in human melanocytes. PMID- 8512222 TI - BisMSH-DTPA. A potential imaging agent for malignant melanoma. PMID- 8512221 TI - Human melanocytes express functional melanocyte-stimulating hormone receptors. PMID- 8512223 TI - Plasticity and ontogeny of melanotrope D2A dopamine receptor mRNA and isoform protein expression. PMID- 8512224 TI - Synthesis and biological activity of highly tritiated rat/human melanin concentrating hormone. PMID- 8512225 TI - Morphofunctional studies on the neurons producing melanin-concentrating hormone. PMID- 8512226 TI - The isolation and characterization of the major form of N-acetylated beta endorphin from the intermediate pituitary of the toad, Bufo marinus. PMID- 8512227 TI - Secretion of immunoreactive joining peptide by the pituitary of the bullfrog Rana catesbeiana. PMID- 8512228 TI - Simultaneous kinetic imaging of intracellular calcium and pH in single melanotropes. PMID- 8512229 TI - Contrasting actions of melanin-concentrating hormone and neuropeptide-E-I on posterior pituitary function. PMID- 8512230 TI - Melanotropic peptides in insects. PMID- 8512231 TI - Human melanin-concentrating hormone in the human brain. PMID- 8512232 TI - Brain receptors for central and peripheral melanotropins. PMID- 8512233 TI - Evidence for independently regulated secretory pathways in the neurointermediate lobe of Xenopus laevis. PMID- 8512234 TI - Chemistry of melanin-concentrating hormone. PMID- 8512235 TI - Selective innervation of rat pituitary intermediate lobe grafts. PMID- 8512236 TI - D1 dopamine receptor mRNA in B16 mouse melanoma cells. PMID- 8512237 TI - Molecular determinants for cell specificity and glucocorticoid repression of the proopiomelanocortin gene. PMID- 8512238 TI - Pigment-dispersing hormones. PMID- 8512239 TI - Morphofunctional aspects of melanotrophic cells developing in situ and in vitro. PMID- 8512240 TI - Tobacco smoking and nutrition. PMID- 8512241 TI - Adhesion-promoting effects of cigarette smoke on leukocytes and endothelial cells. PMID- 8512242 TI - Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. PMID- 8512243 TI - Cigarette smoking, antioxidants, lipid peroxidation, and coronary heart disease. PMID- 8512244 TI - Cigarette smoking, polyunsaturated fats, and coronary heart disease. AB - The relation between smoking habit and diet was investigated in 910 men and women. Diet was assessed by a self-administered food frequency questionnaire. After adjustment for age, sex, and occupational group, smokers had a substantially higher saturated fat (SFA) intake and much lower polyunsaturated fat (PUFA), principally due to a lower linoleic acid (LA) intake, resulting in a lower P:S ratio compared with never smokers, and these dietary differences remained after adjustment for alcohol consumption, BMI, and energy intake. Smokers also had different food choices obtaining more PUFA from saturated fat products such as dairy foods, lard, and ordinary margarine, and less from concentrated sources such as PUFA margarines and vegetable oils than nonsmokers. The food choices of cigarette smokers leading to a higher SFA and lower PUFA intakes may partly explain their increased risk of coronary heart disease. PMID- 8512245 TI - Potential inhibitors of tobacco carcinogenesis. AB - Tobacco smoking is causally associated with cancer of the lung, upper aerodigestive tract, pancreas, renal pelvis and urinary bladder. Tobacco chewers and especially snuff dippers face an increased risk for cancer of the oral cavity and pharynx. Although cessation of the tobacco habits is the only sure way to avoid an increased risk of tobacco-related cancers, certain modified products should be available to lower the incidence rates for cancer among those tobacco chewers and smokers who are unable to give up their tobacco habits. The modified cigarette has been the first approach toward the reduction of cancer risk. In the case of cancer of the lung, the long-term smoker of low-yield filter cigarettes has a risk reduction of 30-50% over that of the smoker of nonfilter cigarettes; however, the risk of filter cigarette smokers for cancer of the lung and cancer at other sites is still many times higher than that of the nonsmoker. A second modality is the application of natural or synthetic chemopreventive agents. Clinical studies with tobacco users have been primarily limited to the application of beta-carotene and retinoids. Although the data appear encouraging in respect to reducing early lesions in the oral cavity of tobacco chewers and smokers and in respect to second primaries in smokers, the benefits of beta carotene and retinoids are gradually reversed upon withholding these micronutrients. It is understandable that activities in respect to chemopreventive agents in clinical trials on smokers are limited, since cessation of smoking alone leads within only a few years to a significant reduction of the cancer risk. Another reason for the limited interest in clinical trials on smokers may relate to the lack of laboratory data on the actual effects of chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents have been tested in mice and rats which were treated with carcinogenic, tobacco-specific N-nitrosamines (TSNA). The results appear most encouraging in respect to lung tumor reduction. It is hoped that this type of research will gain in interest. Human data suggest that the fat content of the diet influences the cancer risk of smokers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8512246 TI - Pulmonary carcinogenesis and its prevention by dietary polyphenolic compounds. AB - The aims of this study were to define the cumulative exposure of Canadian smokers to NNK and to characterize the efficacy of ellagic acid to inhibit lung tumorigenesis induced by NNK. The sales-weighted average of NNK deliveries from Canadian cigarettes was 73.2 ng/cigarette. NNK deliveries were highly correlated to declared tar values and were linear with puff volumes between 20 and 50 ml. Ellagic acid inhibited lung tumorigenesis induced by NNK in A/J mice. This inhibition was related to the logarithm of the dose of ellagic acid added to the diet. The biodistribution of ellagic acid was studied in mice gavaged with ellagic acid. Pulmonary levels of ellagic acid were directly proportional to the dose of ellagic acid between 0.2 and 2.0 mmol/kg b.w. PMID- 8512247 TI - Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis by compounds derived from cruciferous vegetables and green tea. AB - We have shown that PEITC and I3C, both of cruciferous origin, inhibited lung tumor formation induced by the tobacco-specific nitrosamine NNK. The inhibition by PEITC is due largely to its inhibitory effect on the enzymes of NNK metabolism, whereas; the inhibition by I3C may be attributed to its ability to induce hepatic enzyme activity of NNK metabolism, which resulted in decreased availability of NNK to the lung. On a molar basis, PEITC is considerably more effective than I3C. PEITC was released upon consumption of watercress. The N acetylcysteine conjugate of PEITC is a promising urinary marker for quantitating uptake of this dietary anticarcinogen in humans. These studies also showed that green tea polyphenol EGCG inhibited the NNK-induced lung tumorigenesis, probably due to its antioxidant property. These studies provide for the first time evidence for the involvement of free radicals in nitrosamine tumorigenesis. The mechanism by which free radicals are generated by NNK treatment is not yet known. The reduced levels of oxidative lesions in lung as a result of EGCG treatment may be related to its ability to reduce reactive oxygen species and/or to chelate iron ion resulting in a decreased production of hydroxyl radicals. Overall, these studies have identified ingredients in cruciferous vegetables and green tea that are inhibitory against lung tumorigenesis induced by NNK in rodents. PMID- 8512248 TI - Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene. AB - Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture. PMID- 8512249 TI - Intragastric nitrosation of nicotine is not a significant contributor to nitrosamine exposure. AB - To determine the potential for intragastric nicotine nitrosation, we carried out a kinetic study of the reaction of nicotine with nitrous acid in aqueous solution. The reaction of nicotine with nitrous acid resulted in the formation of three products, NNA, NNN, and NNK. The three parallel reactions were first order of 10-6 L/mol/s. The optimum pH range for formation of NNA, NNN, and NNK was 2.4 to 3.1. Thiocyanate (100 mM) slightly increased the rate of formation of NNN and NNK but tripled the rate of formation of NNA at pH 3.5 at 37 degrees C. We have also studied the nitrosation of pseudooxynicotine, a bacterial and fungal metabolite of nicotine. This secondary amine nitrosated rapidly to produce NNK. Our proposed mechanism for the conversion of nicotine to NNK includes nine kinetically distinct steps and is in agreement with our experimental results. The rate limiting step involves the formation of nicotine-1',2'-iminium ion. This ion hydrolyzes to form pseudooxynicotine which undergoes rapid, irreversible nitrosation to NNK. Given the very slow rate of nicotine nitrosation, it is unlikely that nicotine itself contributes to exposure to nitroso compounds due to chemically mediated intragastric nitrosation. PMID- 8512250 TI - Micronutrients and their influence on mutagenicity and malignant transformation. AB - Many studies have now indicated that micronutrients, such as the carotenoids, tocopherols, and ascorbic acid, can prevent mutagenesis, genotoxic effects, or malignant transformation in bacteria and mammalian tissue, either in cell culture or in organ culture. In addition, multiple papers report that some of these micronutrients act as anticarcinogenic agents in animals treated with either ultraviolet light, ultraviolet light with chemicals, or chemical carcinogens alone. With respect to the carotenoids, early experiments used pharmacological doses of carotenoids, but more recent reports indicate that relatively small doses can be effective. Inasmuch as these effects are seen with both provitamin A and nonprovitamin A carotenoids, it would appear that these effects are intrinsic to the carotenoid molecule, and not due to the metabolic conversion to retinoids. Partially on the basis of these observations, it has been suggested that the micronutrients may function as chemopreventive agents for reducing the risk of cancer in humans. Numerous human intervention studies are underway to test this hypothesis. PMID- 8512251 TI - Cigarette smoke-induced DNA damage in cultured human lung cells. PMID- 8512253 TI - Vitamin E and smoking and the risk of lung cancer. AB - The hypotheses that the antioxidant vitamin E provides protection against lung cancer and that this hypothetical protection is modified by smoking status were investigated using two different study designs--a cohort study and a nested case control study--among Finnish men aged 15 years and over. In the cohort study the association between vitamin E intake and lung cancer risk was studied among 5,254 individuals with 121 lung cancer cases that occurred during a 19-year follow-up, and in the nested case-control study the association between serum vitamin E level and lung cancer risk was studied using 144 lung cancer cases and 270 matched controls as a basis. There was a significant inverse association between vitamin E status and lung cancer occurrence among nonsmokers but not among smokers in both designs. The relative risk of lung cancer between the lowest and highest tertiles of vitamin E intake was 3.3 among nonsmokers and 0.8 among smokers. The corresponding results for serum vitamin E were 6.6 and 0.8, respectively. Nonsmokers with simultaneously low serum levels of vitamin E and other micronutrients (i.e., beta-carotene, retinol and selenium) had a 12-fold greater risk of lung cancer in comparison with men having more satisfactory levels. The corresponding number among smokers was three. The results suggest that vitamin E status is primarily associated with lung cancer risk among nonsmokers. Firm conclusions can, however, be drawn only on the basis of intervention trials. PMID- 8512252 TI - Molecular and biochemical reprogramming of oncogenesis through the activity of prooxidants and antioxidants. AB - The antioxidant alpha-tocopherol and the weaker antioxidant and prooxidant chemopreventative, beta-carotene have been shown to inhibit tumor cell growth in vivo and in vitro. In some epidemiologic studies their serum levels were demonstrated to be inversely related to the incidence of malignant tumor. We hypothesized two basic pathways triggered by antioxidants and prooxidants, which resulted in the control of tumor cell growth. These included changes in phosphorylation and ultimately transcription. Specifically, the prooxidant beta carotene treatment produced an oxidative stress resulting in the selective induction of heat shock proteins (hsps). These proteins and other proteins that were possibly oxidized were associated with the increased expression of cyclins (A and D) and increased cdc2 kinase expression. An increase in expression of phosphoproteins, such as p53 (tumor suppressor form) was also discerned. The level of expression for the transcription factor c-fos was reduced. Growth factors that contribute to tumor cell growth were also reduced. Increased DNA fragmentation, depression of proliferation and intracellular calcium levels, the accumulation of tumor cells in G0-->G1, and morphologic changes, were consistent with programmed cell death. Antioxidants such as alpha-tocopherol bound to membrane-associated proteins could inhibit the development of peroxidation products (hydroxyl radicals (.OH)), which attack proteins and modify their function and promote their degradation. Some kinases such as, cdc2 may be increased in activity, which would explain the observed increased expression of tumor suppressor p53, the accumulation of the tumor cells in G1 of the cell cycle and the inhibition of tumor cell proliferation. A reduction in oxidant radicals could also reduce transcription factor products, such as c-myb. Indirectly this result may occur through changes in nuclear translocation (signaling) NF-AT or the Rel-related family of transcription factors, including NF-kB (p50 or p65) or inhibition of immunophilin-calmodulin activity. Although the data remains fragmentary there are common points for control for tumor cell growth resulting from the effects of alpha-tocopherol or beta-carotene treatment. These changes involve phosphorylation and protein expression. Ultimately there is a reduction of important transcription factor protein products, a reduction in response to growth factors, and suppression of cell proliferation, resulting in increased control of the cell cycle. PMID- 8512254 TI - Cigarette smoking and oxidative damage in the lung. AB - Cigarette smoke contains a large variety of compounds, including many oxidants and free radicals that are capable of initiating or promotes oxidative damage. Also, oxidative damage may result from reactive oxygen species generated by the increased and activated phagocytes following cigarette smoking. In vitro studies are generally supportive of the hypothesis that cigarette smoke can initiate or promote oxidative damage. However, information obtained from in vivo studies is inconclusive. Contrary to expectations, the levels of lipid peroxidation products were found to be decreased or unchanged in the lungs of chronically smoked rats. Metabolic adaptation, such as accumulation of vitamin E in the lung, and increased activities of superoxide dismutase in alveolar macrophages and pulmonary tissues of chronically smoked animals may enable smoked subjects to counteract oxidative stress and to resist further damage to smoke exposure. However, it is also possible that the metabolic adaptation may be secondary to inflammatory response and injury repair process following smoking exposure. More studies are needed to better understand the role of oxidative damage in the etiology of smoking-related disorders. PMID- 8512255 TI - Membrane damage from lipid oxidation induced by free radicals and cigarette smoke. PMID- 8512256 TI - The French paradox: dietary factors and cigarette smoking-related health risks. PMID- 8512257 TI - Nutrient and food group intake by tobacco use status: the 1987 National Health Interview Survey. PMID- 8512258 TI - Smoking, alcohol, and plasma levels of carotenes and vitamin E. AB - Taken together, the results from these studies clearly indicate that alcohol and cigarette smoking may both decrease serum or plasma beta-carotene levels after controlling for dietary intake and lipid profile. The variation among studies in the magnitude of the association and statistical significance may reflect, in part, the joint distribution of smoking and alcohol intake in the populations. For example, in the supplementation study reported by Costantino, 89% consumed alcohol, considerably higher than population averages. Further, one-third of the men in that study consumed more than 65 ml (52 gm) of pure alcohol per day. This contrasts with the data from the Health Professionals Follow-up Study, where the mean intake of alcohol was 12.3 gm/day with a standard deviation of 15.8. Even lower alcohol intakes are reported in women, further attenuating the relation and the statistical power to detect a relation between alcohol and beta-carotene levels. Measurement error in assessing dietary intake of beta-carotene could explain some of the association between smoking, alcohol and serum beta-carotene levels because of incomplete control (residual confounding) of dietary intake. Methods for statistically adjusting for error in measurement have not yet been implemented in analyses of this nature. PMID- 8512259 TI - Estimating ascorbic acid requirements for cigarette smokers. AB - This analysis of a large, population based, cross-sectional survey demonstrates that the association of smoking with decreased serum ascorbic acid (AA) levels is independent of the reduced AA intake found in smokers. Smokers have a threefold higher incidence of low serum AA levels (< or = 11 mumol/L) which could place them at increased risk for the clinical manifestations of AA deficiency. Smokers not taking vitamin supplements who consumed less than 15 servings weekly of fruits and vegetables were especially prone to have serum AA levels less than 11 mumol/L. An AA intake of > or = 200 mg was necessary to provide smokers with equivalent protection from hypovitaminosis AA as had nonsmokers whose AA intake exceeded the recommended dietary allowance (RDA [60 mg]). This level of dietary AA intake is considerably higher than the newly increased RDA for smokers of 100 mg. Although the simplest and most direct method to increase the low serum vitamin C levels found in many smokers would be to stop smoking, markedly increasing dietary AA consumption is appropriate when this is unsuccessful. However, if dietary modification fails to sufficiently increase AA intake, then vitamin supplementation may be necessary to significantly reduce the high prevalence of hypovitaminosis AA present in smokers. PMID- 8512260 TI - Antioxidant vitamin intakes in Scottish smokers and nonsmokers. Dose effects and biochemical correlates. PMID- 8512261 TI - Cigarette smoke-mediated oxidant stress, phagocytes, vitamin C, vitamin E, and tissue injury. PMID- 8512262 TI - Why is smoking a major risk factor for coronary heart disease in hyperlipidemic subjects? PMID- 8512263 TI - Cigarette smoke oxidation of human plasma constituents. AB - In vitro exposure of fresh human plasma to cigarette smoke (CS) was used as a model for reactions that could be occurring in CS-exposed respiratory tract lining fluids (RTLFs) and lung parenchyma. The central focus of this model was to characterize the consumption of endogenous plasma antioxidants in relationship to the appearance of oxidized proteins and lipids as a consequence of exposure to CS, or to aldehydes present in CS. The amelioration of CS-induced protein and lipid oxidation in plasma by the addition of selective exogenous antioxidants was also assessed. We found that: (i) exposure of human plasma to gas phase CS causes both lipid peroxidation and protein oxidation, and endogenous ascorbic acid protects against lipid, but not protein, oxidation; (ii) whole CS causes protein oxidation, but does not induce lipid peroxidation; (iii) addition to plasma of aldehydes known to be present in CS causes protein damage, but does not induce either lipid peroxidation or oxidation of ascorbic acid; and (iv) exogenously added dihydrolipoic acid (DHLA) preserves ascorbic acid levels in plasma exposed to the gas phase of CS, and protects, to some extent, against lipid peroxidation; DHLA also protects against protein oxidation, whereas added glutathione (GSH) only protects against protein, but not lipid, oxidation. PMID- 8512264 TI - Cigarette smoke, LDL and cholesteryl ester accumulation in macrophages. Implications for atherosclerosis. PMID- 8512265 TI - Function of vitamin E and zinc in maintaining endothelial integrity. Implications in atherosclerosis. PMID- 8512266 TI - Difficulties in endoscopic removal of Teflon granulomas of the vocal fold. AB - The difficulties in treating granulomas resulting from Teflon injection into the vocal fold are underreported in the literature. We have reviewed our experience with nine patients undergoing 27 procedures for Teflon granuloma. Two patients required tracheotomy before undergoing endoscopic granuloma removal because of airway compromise, and a third required urgent tracheotomy following endoscopy. One of the patients requiring elective tracheotomy had a granuloma that extended across the midline to the contralateral arytenoid, causing its fixation. Arytenoidectomy was required for decannulation in this patient. In all but one patient the granuloma nearly completely replaced the thyroarytenoid muscle. This extensive involvement often precludes the adequate excision of the granuloma in a single procedure; however, the microflap technique allows mucosal preservation to facilitate future procedures. In some cases the granuloma destroys large amounts of mucosa, and a microflap cannot be elevated and saved. The difficulties of excision are related to the near-total replacement of the thyroarytenoid muscle by granuloma. This paper will help the otolaryngologist--head and neck surgeon understand this destructive process and the resulting difficulties in surgical rehabilitation. PMID- 8512267 TI - Survival of Scarpa's ganglion in the profoundly deaf human. AB - The electrically evoked auditory brain stem response in some cochlear implant patients may be confounded by evoked potentials generated by vestibular neurons. The magnitude of this contribution to the response from the vestibular system is unknown, in part because the survival of cells within Scarpa's ganglion in profoundly deaf humans is unknown. Therefore, we undertook a quantitative study of Scarpa's ganglion in 48 deaf subjects who in life would have been candidates for cochlear implantation and in 5 subjects with normal hearing. The numbers of residual cells in both Scarpa's ganglion and the spiral ganglion in deaf subjects were significantly less than in individuals with normal hearing. Bivariate analysis demonstrated a highly significant positive correlation between cell counts of Scarpa's ganglion and the spiral ganglion. The durations of hearing loss and of profound deafness were negatively correlated with Scarpa's ganglion cell counts. However, in contrast to spiral ganglion cell survival, the cause of profound deafness did not predict the number of Scarpa's ganglion cells. Multiple linear regression analysis using a variety of clinical parameters demonstrated that the best predictor of the number of Scarpa's ganglion cells in profoundly deaf humans was the number of remaining spiral ganglion cells. PMID- 8512268 TI - Atelectasis of the maxillary sinus with enophthalmos and midface depression. AB - Enophthalmos previously has been reported to be a rare complication of maxillary sinus mucoceles. We report three patients treated by the senior author (T.C.C.) over a 2-month period for enophthalmos or obvious deformity of the midface associated with complete opacification of the maxillary antrum. Most previous authors have stressed the role of chronic pressure necrosis or osteitis leading to bone destruction, with primary involvement of the orbital floor. No patients in this series had symptoms typical of maxillary sinus mucoceles. Two of our three patients presented with minimal symptoms of chronic infection. There was inward collapse of the anterior, superior, lateral, and medial walls of the maxillary sinus, with no radiographic or intraoperative confirmation of bone destruction. We speculate that this process may be the result of chronic maxillary hypoventilation with subsequent atelectasis of the antrum secondary to chronic negative pressure. All patients had obstruction at the osteomeatal complex and were treated by endoscopic enlargement of the natural maxillary ostium. PMID- 8512269 TI - Far-advanced otosclerosis. AB - Profound deafness has received increasing attention in recent years, largely because of the availability of cochlear implants. Consequently, it is especially important for otolaryngologists to remember that a "blank" audiogram does not necessarily mean total or even profound deafness. Patients with far-advanced otosclerosis may have no measurable hearing with routine audiometric testing even in the presence of serviceable sensorineural hearing. Review of nine patients (10 ears) who underwent stapedectomy from 1980 to 1987 reveals that seven of the nine (78%), who had been unable to use a hearing aid preoperatively, obtained serviceable hearing with hearing aids following surgery. Otolaryngologists should depend on a good history and tuning fork examination to avoid being misled by the audiogram, and should not hesitate to offer stapes surgery to patients with far advanced otosclerosis. PMID- 8512270 TI - Gustatory otorrhea: Frey's syndrome of the external auditory canal. AB - A case of Frey's syndrome of the external auditory canal is reported. The patient presented with unilateral gustatory otorrhea and thickened external auditory canal skin. Histopathologic examination of the canal skin showed sudomotor gland hyperplasia. Symptoms were relieved with canal skin excision and skin graft. PMID- 8512271 TI - Airway complications in thyroid surgery. AB - Perioperative and postoperative morbidity and mortality were studied in a series of 3,008 thyroidectomies. Compressive symptoms, frequent in substernal and cancerous goiters, were present in 11.0% of the patients, although a low rate of dyspnea (2.7%) was observed. In large goiters, some orotracheal intubations were difficult. In such cases, the transtracheal approach can also be difficult, so failure should be anticipated. Postoperative causes of respiratory obstruction included local hemorrhages, bilateral recurrent nerve palsies, and laryngeal edema. A tracheal collapse was not observed. These respiratory obstructions led to repeat surgery in 11 patients, tracheostomy in 3, and temporary reintubation with steroid therapy in 1. The recurrent laryngeal nerve, which may have been affected preoperatively, was found to be damaged postoperatively in 0.5% of the patients with benign goiters, compared to 10.6% of the patients with thyroid cancer. In this last group a bilateral palsy was observed in 3 cases with prolonged or extensive surgery. After these short-term orotracheal intubations (114 minutes on average), injuries of the airway caused by the endotracheal tube were found in 4.6% of the patients. PMID- 8512272 TI - Cochlear wall titanium implants for auditory nerve stimulation. AB - Genetically deaf dalmatian dogs and ototoxically deafened macaque monkeys were implanted with electrodes housed in cochlear wall titanium implants to assess long-term stability, tolerance, and performance. Short-term human implantation, followed by trials of stimulation, was performed in 4 unilaterally deaf patients. In the dog experiments, cochlear wall electrode stimulation produced consistent electrophysiologic thresholds that were higher, by approximately 6 dB, than those obtained with bipolar scala tympani stimulation. Clinical testing revealed electrically evoked middle latency response, auditory brain stem response, and/or behavioral detection responses in 3 of 4 patients, at levels below those for facial nerve activation and pain sensation. Electrode place discrimination studies, with controls for loudness cues, revealed near-perfect discrimination in a monkey subject. Eleven of the 12 animal implants were found to be rigidly fixed in the cochlear bone, with direct contract between bone and implant over 8% to 23% of the implant surface for the 6 implants examined in detail. These results suggest that long-term fixation of titanium cochlear wall implants occurs by virtue of intimate implant-bone contact in restricted areas. This approach to prosthetic stimulation demonstrates encouraging performance characteristics in achieving auditory activation. PMID- 8512273 TI - The Hayek oscillator: a new method of ventilation in microlaryngeal surgery. AB - The Hayek oscillator is an externally (body) mounted cuirass ventilator used in the intensive care unit. We have used it to ventilate patients undergoing microlaryngeal surgery. It was found to be a relatively safe method of ventilation in these cases, with the advantage of dispensing with any form of endolaryngeal or endotracheal intubation. PMID- 8512274 TI - Regeneration of maxillary sinus mucosa following surgical removal. Experimental study in rabbits. AB - A rapid regeneration of the epithelium takes place in the maxillary sinus in rabbits after experimental operative removal of the mucosa. Two weeks postoperatively the previously denuded areas have reepithelialized. The subepithelial glands, however, do not seem to regenerate. The normal sinus mucosa contains numerous serous glands in the lamina propria, but in the regenerated mucosa these glands are replaced by dense connective tissue. Atypical glands and polyp formations are sometimes encountered, but goblet cells are sparse. Furthermore, the sinus cavity on the operated side is reduced in size compared with the nonoperated side because of fibrosis and periosteal reactions including bone degradation and neogenesis. This study indicates that although the mucosa is reepithelialized within 2 weeks, the regeneration of the lamina propria is incomplete, and reactive cellular processes such as bone remodeling, fibroblast proliferation, and formation of polyps and "atypical glands" are characteristic of regenerating mucosa. PMID- 8512275 TI - Animal model for persistent tympanic membrane perforations. AB - Topically applied hydrocortisone was used to develop an animal model for persistent tympanic membrane (TM) perforations. Hydrocortisone suspension was applied on the margins of TM perforations of standardized size in rats once daily for 10 days. The healing patterns of the TMs were mapped weekly and, when the perforations were about to close, daily. After 50 days, all hydrocortisone treated perforations were open, whereas the controls closed within 9 to 12 days. At 3 months, when one third of the perforations still were open, the TMs were studied by otomicroscopy and light microscopy. All TMs were thickened and covered by keratin and wax. The thickened epidermal layer at the border of the TM perforations that remained open also draped the surface of the perforation facing the middle ear cavity. The thickened connective tissue layer contained abundant fibroblasts with their axes of length oriented at random. Both application of 1.4% hyaluronan and wounding of the perforation border enhanced the healing rate of the hydrocortisone-induced chronic TM perforation. PMID- 8512276 TI - Magnetic resonance imaging of bilateral familial paragangliomas. PMID- 8512277 TI - Facial nerve neuroma. AB - Facial nerve neuromas are an unusual cause of facial nerve dysfunction and hearing loss. As clinical manifestations do not accurately reflect tumor extent, imaging techniques can greatly assist the clinician in appropriate diagnostic evaluation and management. PMID- 8512278 TI - Tumefactive fibroinflammatory lesions of the head and neck. AB - Tumefactive fibroinflammatory lesions of the head and neck are idiopathic, histologically benign, tumor-forming lesions that clinically stimulate malignancies. Their histopathologic appearance is nearly identical to that of fibrosclerotic lesions of the mediastinum and retroperitoneum and Riedel's thyroiditis, and in some cases, a congeneric (periarteritis) origin is postulated. There is no optimum treatment, and recurrence and persistence are common. The suggested initial treatment is corticosteroid administration. PMID- 8512279 TI - Penetrating trauma of the jugular foramen. PMID- 8512280 TI - Acquired laryngomalacia: epiglottis prolapse as a cause of airway obstruction. PMID- 8512281 TI - Plasma cell granuloma of the middle ear and mastoid. Case report. PMID- 8512282 TI - Infection of mammary prostheses: a survey and the question of prevention. AB - Seventy-three plastic surgeons reported 60 early and late mammary implant infections among 54,661 implantations. Smooth, textured, and polyurethane-coated implants had similar infections rates (respectively, 0.06%, 0.16%, and 0.12% for augmentations and 0.6%, 0.4%, and 0.3% for reconstructions including revisions and expansions). Insertion routes and implant placements had no influence on infection rates. Causative bacteria included Staphylococcus aureus and S. epidermidis, Streptococci A and B, enterobacteria, Klebsiella, Pseudomonas, and mycobacteria. Most surgeons followed a regimen of topical and/or systemic prophylaxis. Some (approximately 20%) used the Dolsky insertion sleeve. Whereas smoking, obesity, and diabetes did not significantly predispose to infection, the following did: skin atrophy and scarring, corticosteroids in subglandular augmentation, additional simultaneous surgery, pregnancy, preceding lactation, and vigorous exercising, massage, and trauma postsurgically. Few late implant infections were recorded resulting from bacterial milk duct invasion or hematogenously from antecedent infection foci. The need for and the possibilities of preventive measures are critically discussed. PMID- 8512283 TI - Total versus partial musculofascial coverage for steroid-containing double-lumen breast implants in augmentation mammaplasty. AB - The use of intraluminal steroids in double-lumen breast implants is effective in preventing fibrous capsular contraction around the implant. This technique has not been accepted widely, however, and remains controversial primarily because steroid-related complications, including extrusion, late inferior migration, and atrophy of the skin, have been associated with their use. This nonrandomized retrospective study of 76 patients (146 breasts) who underwent submuscular augmentation of the breast through inframammary and periareolar incisions compares results after total musculofascial coverage of the implant with partial muscle coverage of the implant. In patients with partial muscle coverage of the implant, 7.8% steroid-related complications were observed. In the group with total musculofascial coverage of the implant, no steroid-related complications and no symptomatic contractions of the capsule were observed. Our study suggests that total musculofascial coverage provides a statistically significant margin of protection from steroid-related complications compared with techniques using only partial muscle coverage of the implant in patients who underwent cosmetic augmentation mammaplasty. PMID- 8512284 TI - Speech and velopharyngeal function following maxillary advancement in patients with cleft lip and palate. AB - The influence of maxillary advancement by osteotomy on speech was examined in 10 patients with cleft palates (6 males, 4 females). Ages at the time of surgery ranged from 16 to 26 years (mean, 19.5 yr). LeFort I and II osteotomies were performed in 9 patients and 1 patient, respectively. Preoperatively and postoperatively, hypernasality, nasal emission on pressure consonants, and articulation disturbances were evaluated perceptually, and velopharyngeal function was evaluated by lateral cephalographic and nasopharyngoscopic studies. Hypernasality, which had been judged preoperatively to be absent or slight in 1 patient each, remained unchanged after surgery, whereas the remaining 8 patients showed increased hypernasality after surgery. Nasal emission showed a similar tendency. Articulation errors were not improved postoperatively. Lateral cephalograms recorded from the patients with increased hypernasality showed increases in the shortest palatopharyngeal length and in the soft-palate-length- to--pharyngeal-depth ratio. Also, deterioration in velopharyngeal closure was noted postoperatively compared with preoperatively by nasopharyngoscopy in the majority of patients with increased hypernasality. PMID- 8512285 TI - Early radical treatment of pancraniofacial synostosis. AB - Premature fusion of all major cranial and facial sutures, termed pancraniofacial synostosis by us, was first described as "Kleeblattschadel deformity," but can also be found in anomalies such as Crouzon's disease, Apert's syndrome, Pfeiffer's syndrome, and severe forms of plagiocephaly. This rare craniofacial anomaly often presents an immediate threat to life right after birth. Early subtotal craniectomy frequently combined with frontoorbitofacial advancement must be performed to decrease intracranial pressure, preserve vision, and open up the blocked upper airway. Concomitant hydrocephaly is shunted preoperatively for internal decompression. Eleven patients with pancraniofacial synostosis underwent craniofacial surgery in infancy or early childhood. Only shunting of the hydrocephalus was done in 1 child. Two children died in the course of an emergency procedure and 2 children died after secondary operations for miniplate removal and revision of a valve shunting the hydrocephalus several months after the initial successful craniofacial surgery. The remaining 8 children have developed satisfactorily so far. Further corrective surgeries had to be performed in 2 patients. Good functional and aesthetic improvement could be obtained. In view of the high mortality especially after emergency procedures, we believe that early total craniofacial mobilization should be reserved for severe cases where the natural course is dismal without immediate intervention and temporary procedures such as shunting and tracheostomy are not sufficient. Elective surgeries after the age of 3 months can be performed safely in milder cases. PMID- 8512286 TI - The role of the bone-gallium scan in sternal osteomyelitis. AB - Sternal osteomyelitis is an uncommon but serious complication of the median sternotomy incision. Between 1982 and 1990, 160 patients with sternal osteomyelitis and wound dehiscence were treated with sternal debridement and pectoral muscle flap closure at The Toronto Hospital. Most of these wound infections were clinically obvious, and the need for surgical treatment apparent. In a small number of patients, however, the extent of the infection was more difficult to determine clinically. In this subset of patients, the interpretation of the bone-gallium scan was important in determining the presence or absence of bone infection and the probability of successful treatment without surgery. In this study, we review our findings at the time of surgery and compare them with the preoperative information available from the bone-gallium scan. The limited literature on this topic is reviewed. In this group of patients, we found the bone-gallium scan was not helpful in clinical management. PMID- 8512287 TI - Phalloplasty in female-to-male transsexuals: what do our patients ask for? AB - Although the surgical goals of phalloplasty in female-to-male transsexuals have repeatedly been described, the requests by the patients themselves have never been assessed and evaluated properly. To obtain information on their desiderata in this matter a questionnaire was sent to 200 subjects. The answers in the 150 returned questionnaires made us conclude that the 79 subjects (52%) who seek phalloplasty express the following requests as to their external genitalia: a scrotum (96%), a glans (92%), rigidity (86%), and an aesthetically appealing look either while wearing a tight swim suit (91%) or being nude (81%). All but 1 patient wanted to be able to void in a standing position. We add minimal disfigurement and no functional loss in the donor area as two of the goals of phalloplasty. PMID- 8512288 TI - Obtaining rigidity in the neophallus of female-to-male transsexuals: a review of the literature. AB - In phalloplasty, the use of transplants and implants to obtain sufficient rigidity allowing for sexual penetration is difficult and often has resulted in complications and failure. Resorption, curving, and fracture of autologous cartilage and bone transplants are reported, and rigid implants have a tendency to erode and extrude. Besides, a constantly rigid phallus may serve as a source of embarrassment to the patient. On the other hand, hydraulic prostheses frequently show mechanical failure compared with nonhydraulic implants. For these reasons, some authorities have their patients use external devices for erection. Others fully rely on edema, scar fibrosis, or congestion to give sufficient rigidity. In this review, the literature on baculum implantation--on the use of external devices as well as on the use of no stiffener at all--is discussed. PMID- 8512289 TI - A biochemical and histological comparison of vascularized and free fat grafts in the rabbit. AB - An experimental study, in 20 rabbits, of free (i.e., nonvascularized) versus vascularized fat tissue transfer was undertaken. The purpose was to study the biochemical and histological changes in the two types of fat grafts compared with normal fat tissue over a period of 16 weeks. The left inguinal fat pad was transferred freely to the contralateral side; the right inguinal fat pad was transferred to the left side where the pedicle was anastomosed to the left femoral artery and vein. Macroscopically, at all postoperative times, the transferred free fat had a harder consistency, was more adherent to the surroundings, and was less pliable than the vascularized fat, which was similar to normal fat. Histologically, free fat tissue displayed near complete degeneration at 2 and 4 weeks, but recovered to essentially normal appearance by 16 weeks. Apart from some degeneration evident at 2 weeks, vascularized fat tissue retained a normal histological appearance to 16 weeks. Biochemical analysis demonstrated minor increases of collagen deposits in free fat grafts, but negligible changes were observed in the vascularized fat grafts. Free fat grafts were significantly dehydrated relative to the vascularized fat grafts and control fat (p < 0.01). Based on these findings, we suggest that the clinical use of vascularized fat tissue transfer would be preferable in most circumstances to free fat transfer. PMID- 8512290 TI - A study of simplified porcine skin preservation. AB - The study of preserved porcine skin was done by using split-thickness skin grafts of pigs weighing approximately 25 to 30 kg. The harvesting of split-thickness skin grafts was performed under aseptic and antiseptic conditions. The povidone iodine solution and 0.25% acidified sodium hypochlorite solution were used before immersion of the skin in 90% glycerine solution. Prepared skin graft was stored in the freezer compartment of a home refrigerator. Serial studies of the bacteriology and the histology of specimens were performed monthly for 12 months. No bacterial organisms were found during the study. The integrity of the skin lasted up to 5 months, however, the property of the preserved skin was as good as the other biological dressing even after 6 months. This simple, low-cost procedure is useful for restoring allografts or even autografts in a hospital without conveniences or adequate facilities. PMID- 8512291 TI - Steam press burns of the hand. AB - Steam presses pose an occupational hazard to workers in the dry cleaning industry. Three patients with thermal burns to the hand from steam press accidents were recently treated at this institution. Each patient sustained deep second and third degree burns to the dorsum of the hand. Two patients required split-thickness skin grafts and have retained full range of motion and returned to full employment. One patient sustained destruction of extensor tendons and required a groin flap for coverage. Late tendon reconstruction will be necessary. Investigation revealed that older steam press models do not have an emergency release lever in case of accidental closure on a worker's hand. Although newer models are equipped with a thigh-activated emergency release lever, a contact burn remains likely if the press closes on the operator's hands. Some of the newest models have an attached safety bar that prevents the press from closing on the operator's hands. It is recommended that older models either be modified with the attachment of a safety bar or replaced entirely. PMID- 8512292 TI - Amyloid plaque of the lower eyelid: a patient report and review of the literature. AB - Localized conjunctival amyloid plaque is a rare disorder. It usually remains localized and is only rarely associated with systemic disease, unlike cutaneous amyloid deposits of the eyelid. The pathogenesis is unknown, but appears to be related to long-standing chronic inflammation. There may be a localized immunological disorder or an underlying systemic disease in rare instances. Because of this possible association, all patients should undergo through physical examination with close follow-up to rule out systemic disease. Plastic surgeons need to be aware of this lesion because the diagnosis is easily missed, clinically. The primary clinical working diagnosis before biopsy is a neoplasm, and recognition of this entity can prevent unnecessarily radical surgery. PMID- 8512293 TI - Long-term complications of reconstruction of the heel using a digitorum brevis muscle flap. AB - Seven patients who had surgery for malignant skin tumors of the heel were followed up for several years. The reconstructive procedure performed was repair of the large skin defect after excision of a tumor, by using a flexor digitorum brevis muscle flap and an overlying free graft. Although this procedure is a good method without any serious complications, no long-term follow-up data supporting this opinion have been reported. In this study, plantar flexion of the toes and flattening of the plantar arch appeared 3 months after surgery and developed for 1 year, and the patients complained of easy fatigability in walking and difficulty in going up stairs. These sequelae were probably due to sacrifice of the flexor digitorum brevis muscle. We feel that this procedure should be replaced by another procedure that does not sacrifice any muscle, for example, that using a medial plantar flap. PMID- 8512294 TI - The triceps muscle flap for axillary contracture release. AB - Previously overlooked, the concept of a triceps muscle flap has been recently proven valid. By using only the long head portion, necessary function preservation may be achieved. A distinct proximal neurovascular source to this component alone allows an axis of rotation at the level of the teres major muscle. This permits transposition either in an anterior or posterior direction as a local muscle flap that has usefulness, albeit in a secondary role, for axillary reconstruction such as commonly required as a sequela to burn contracture. PMID- 8512295 TI - Surgical treatment of tuberous breasts with bilateral mega-areola with a periareolar scar technique. AB - The case of a young women with huge bilateral areolas and tuberous breasts is presented; how this was surgically treated with a periareolar scar technique is described. This technique, previously presented by a Brazilian plastic surgeon, Joao Carlos Sampaio Goes, was chosen as the best indicated for this woman, to obtain reduction of the large, pigmented areas and a solution to the tuberous breasts. PMID- 8512296 TI - Use of tissue expanders in reconstruction after excision of multiple large silicone granulomas. AB - We present a case rare for its extensive nature with symptomatic silicone granulomas and for the various extensive reconstructive techniques using tissue expansion in several areas. Although the course of surgical rehabilitation was extensive and prolonged, it was initiated and tenaciously pursued by the woman and her husband who initially requested surgery only for relief of pain in the areas of the buttocks and groin. The eventual results achieved were gratifying to the woman. PMID- 8512297 TI - Magnetic resonance imaging findings of craniofacial fibrous dysplasia. AB - There have been few reports in the literature concerning the magnetic resonance imaging (MRI) appearances of fibrous dysplasia. We reviewed MRIs of 4 patients with craniofacial lesions. Using a 1.5-T Signa Unit (General Electric, Milwaukee, WI), both T1- and T2-weighted MRI scans were performed. In our 4 patients, the fibrous dysplastic lesions were characterized by a decreased signal on both T1- and T2-weighted images. And all lesions had sharply demarcated borders. The fine image of fibrous dysplasia by MRI is extremely useful, not only as a diagnostic aid, but also as an invaluable guide to surgery. PMID- 8512298 TI - Free flap chest wall reconstruction for recurrent breast cancer and radiation ulcers. AB - Pedicled myocutaneous flaps are the established first choice for soft tissue coverage of major chest wall defects. In some patients, this alternative is not available because the flap itself or its blood supply may be included within the field of surgical resection, the flap may have been used previously, or the defect is too large or extends past the reach of the flap. In these patients, free flaps can be used to provide adequate soft tissue coverage. This report examines 7 women with major full-thickness chest wall defects treated with free flap soft tissue coverage. Either a rectus abdominis (6 women) or a latissimus dorsi myocutaneous free flap (1 woman) was used. There were no flap failures. Permanent protection of prosthetic material used to stabilize the chest wall was provided in all women. Only 1 woman experienced delayed wound healing. Secondary procedures were not required in any patient. Myocutaneous free flaps provide reliable single-stage soft tissue coverage for large chest wall defects that are not suited to reconstruction with pedicled myocutaneous flaps. PMID- 8512299 TI - Hellfire and explanation. PMID- 8512300 TI - Energy as a central factor in the self-assessment of health. AB - This article explores the role of energy in conceptualization of health, based on self-reported health ratings in 310 women (master's-prepared nurses) ages 50 to 70 years. The health self-assessment instrument consists of 1 global and 10 specific items. The item energy level emerged as central--loading on both the psychosocial health and physiologic health factors and accounting for 48% of variance of Global Health Self-Assessment. These findings build on the World Health Organization definition of health as a synthesis of psychosocial and physiologic well-being; energy level is key to an integrated view of health. PMID- 8512301 TI - Psychoimmunologic effects of therapeutic touch on practitioners and recently bereaved recipients: a pilot study. AB - The purposes of this descriptive pilot study were to address conceptual inconsistencies and several other methodologic problems identified in previous Therapeutic Touch (TT) research, while also providing direction for future TT studies by attempting to determine the appropriateness and suitability of a combination of psychologic and immunologic measures in the ongoing empiric evaluation of TT. Research questions were derived from a unitary perspective. Data on both practitioners and recipients were collected and examined for patterns and relationships. Changes that may be related to TT were observed in immunologic, psychologic, and unitary measures. Directions for future research within a unitary framework were postulated. PMID- 8512302 TI - Music and pattern change in chronic pain. AB - The purpose of this study was to investigate the use of music as a unitary transformative means of altering the perception of chronic pain among women with rheumatoid arthritis within the context of Newman's model of health as expanding consciousness. In this repeated measures investigation, 30 women diagnosed with rheumatoid arthritis for a minimum of 6 months, responded to the McGill Pain Questionnaire prior to listening to music of their choice, during music, and 1 to 2 hours after completing the intervention. Data were analyzed according to the Number of Words Chosen (NWC) and the Pain Rating Index-Rank [PRI(R)] of the McGill Pain Questionnaire. The results of this study support the use of music as a unitary-transformative intervention. PMID- 8512303 TI - Exploration of body listening: health and physical self-awareness in chronic illness. AB - This phenomenologic study explored how healthy and chronically ill adults understand their body experience. Nine healthy adults and nine chronically ill adults (asthma or multiple sclerosis) were interviewed and asked to keep a 6-week diary. Using Colaizzi's method of data analysis, significant statements from all three groups were collated and analyzed for formulated meanings. The resultant body paradigm is defined as the person's explanatory model of who she or he is physically and is the result of past body experiences, shared body experiences of others while growing up, perceived circadian rhythms and personal gnosis. Perception of energy patterns was central to all three groups, and chronically ill informants described adapting to a new body paradigm. PMID- 8512304 TI - Human energy fields and birth: implications for research and practice. AB - This article reviews nursing and related theories of human energy fields and their relevance for care of women in pregnancy and birth. Alternative nursing activities based on human and environmental energy field concepts are presented and implications for future nursing and midwifery research and practice are discussed. PMID- 8512305 TI - A framework for the study of childbearing fatigue. AB - Accounts of fatigue in childbearing women are identified in clinical reports, maternity textbooks, and studies. However, limited conceptual clarification or empiric research directed at mothers' fatigue during childbearing has been undertaken. To better understand fatigue, factors in the childbearing woman's life that are thought to predispose her to fatigue were identified; also delineated were the potential effects of fatigue on maternal performance. The framework that emerged, representing insights from childbearing and fatigue literature, is designed to serve as a guide to research that will add to understanding of childbearing fatigue and how it can be prevented or ameliorated. PMID- 8512306 TI - Feminist ethics and cultural ethos: revisiting a nursing debate. AB - In this article the author re-examines from a feminist perspective the now well known debate between Yarling and McElmurry and Bishop and Scudder. The central point of this critique is that a feminist ethics requires we attend to the social and institutional form of life in which given practices exist. The endorsement of a single concept, even the extremely important one of care, is insufficient for a nursing ethics. Without attention to the institutional factors, which support or reform care, we have only a feminine ethics. In this author's view, nursing needs a feminist ethics. PMID- 8512307 TI - Structural thermodynamics: prediction of protein stability and protein binding affinities. AB - The relationships between the structure of a protein and the thermodynamic parameters that determine its stability constitute the focus of attention of an increasing number of research laboratories. Advances in this area have reached the point in which accurate protein stability predictions and interaction energetics based on crystallographic information appear to be within reach. The purpose of this article is to summarize these developments and discuss future goals and trends. PMID- 8512308 TI - Net adenine nucleotide transport in rat kidney mitochondria. AB - This study investigated the hypothesis that changes in the adenine nucleotide (ATP + ADP + AMP) content of kidney mitochondria can occur by a transport mechanism that catalyzes net transfer of adenine nucleotides across the inner mitochondrial membrane. The adenine nucleotide content of isolated kidney mitochondria was 8.23 +/- 0.85 nmol/mg mitochondrial protein. This amount increased or decreased as a function of the external [ATP-Mg] when mitochondria were incubated in phosphate-containing medium. The increases and decreases were inhibited to different extents by 100 microM EGTA (ethylene glycol bis (beta aminoethyl ether) N,N'-tetraacetic acid) or 5 microM carboxyatractyloside (CAT), suggesting two transport mechanisms. The unidirectional components (influx and efflux) of net flux were examined separately for the CAT-insensitive (EGTA sensitive) and CAT-sensitive (EGTA-insensitive) mechanisms. CAT-insensitive adenine nucleotide influx and efflux were stimulated by [Ca2+]free up to 2 microM; for ATP influx, Km was 1.7 mM, Vmax was 3.5 nmol/min/mg protein, and Mg2+ was required. Efflux varied as a function of both the external and matrix [ATP] and was completely inhibited by mersalyl. ATP was a better substrate than ADP, and ADP transport did not require Mg2+. The CAT-sensitive mechanism was characterized by studying phosphate-induced adenine nucleotide efflux. Efflux varied with external [Pi] and with matrix [ATP] and was not inhibited by cyclosporin. The amount of CAT required for maximal inhibition was 800 pmol/mg protein. In contrast to CAT-insensitive efflux, this pathway was only partially inhibited by mersalyl and showed no preference for ATP vs ADP. In conclusion, two distinct mechanisms for net adenine nucleotide transport were demonstrated. Both exchange adenine nucleotides (ATP-Mg or ADP) for Pi. One mechanism is identical to the CAT-insensitive ATP-Mg/Pi carrier known in liver mitochondria; the other is a CAT-sensitive mechanism that is not present in liver and may represent a novel function of the ADP/ATP translocase or another CAT-sensitive carrier. PMID- 8512309 TI - The two cysteine endopeptidases of legume seeds: purification and characterization by use of specific fluorometric assays. AB - Two endopeptidases are present in the seeds of Vigna aconitifolia (moth bean), and their activities increase during germination. One enzyme, which we term "vignain," can be assayed with benzyloxycarbonyl-phenylalanyl-arginyl-7-(4 methyl)coumarylamide as substrate. The second is legumain (EC 3.4.22.34), which can be assayed with benzyloxycarbonyl-alanyl-alanyl-asparaginyl-7-(4-methyl) coumarylamide. The enzymes were purified, and their specificities for substrates and inhibitors were examined. Vignain has properties expected of a cysteine endopeptidase of the papain family, with the exception of a remarkably low reactivity with iodoacetate. Legumain is a very atypical cysteine endopeptidase, being insensitive to inhibition by chicken cystatin and E-64 (L-3-carboxy-2,3 trans-epoxypropionyl-leucyl-amido(4-guanidino )butane), and reacting more rapidly with iodoacetamide than with iodoacetate. We discuss our findings in relation to the literature on the proteolytic enzymes of legume seeds. PMID- 8512310 TI - Chemical modifications of chicken liver pyruvate carboxylase: evidence for essential cysteine-lysine pairs and a reactive sulfhydryl group. AB - Inactivations of chicken liver pyruvate carboxylase with N-(7-dimethylamino-4 methyl-3-coumarinyl)maleimide (DACM) and o-phthalaldehyde (o-PA) have identified cysteine and lysine residues that are essential for catalytic activity. Protection experiments suggest that the modified residues are located in or near the first and second subsites. At a one- to two-fold molar excess over active site concentration, DACM inactivated approximately 80-90% of the pyruvate carboxylase and ADP/Pi linked oxaloacetate decarboxylase activities by forming a sulfhydryl-DACM adduct with a fluorescence excitation maximum at 385 nm and an emission maximum at 476 nm. o-PA reacted with the enzyme by cross-linking lysine and cysteine residues to form an inactive isoindole-enzyme derivative with a fluorescence excitation maximum at 337 nm and an emission maximum at 415 nm. Incorporation of one equivalent of either DACM or isoindole derivative resulted in an 80-90% decrease in all activities involving chemistry at the first subsite, suggesting that the modification of a sulfhydryl group or a cysteine-lysine ion pair in or near the first subsite inactivates the enzyme. A cysteine-lysine ion pair in the first subsite could function to remove the N-1 proton of biotin to yield enol-biotin, which could be readily carboxylated by the carboxyphosphate intermediate. In the reverse direction, a cysteine-lysine ion pair in or near the second subsite has been proposed to enolize biotin prior to carboxylation by oxaloacetate (P. V. Attwood and W. W. Cleland, 1986, Biochemistry 25, 8197-8205). Enzyme modified with 2 equivalents of isoindole retained only 7% of the oxamate induced, ADP/Pi-independent oxaloacetate decarboxylase activity, suggesting that there is at least one essential cysteine-lysine ion pair at or near the second subsite. PMID- 8512311 TI - The construction and expression of chimeric urokinase-type plasminogen activator genes containing kringle domains of human plasminogen. AB - A series of chimeric urokinase-type plasminogen activator (uPA) genes, which contain combinations of kringle domains of human plasminogen (HPg) in place of the uPA kringle (KuPA), has been constructed and expressed. Some of the resulting recombinant (r) variant uPA chimeras contain modules that potentially mediate the macroscopic binding of HPg to its activation effectors, fibrin(ogen) and 6 aminohexanoic acid (EACA). Such binding sites are not possessed by KuPA, but are present in certain of the HPg kringles, viz., kringle 1 (K1HPg), kringle 4 (K4HPg), and kringle 5 (K5HPg). The recombinant (r) chimeras constructed included molecules with replacements of KuPA with K1HPg (r-[KuPA-->K1HPg]uPA), and with KuPA replaced by double kringle combinations of K1HPgK4HPg (r-[KuPA- >K1HPgK4HPg]uPA), K2HPgK3HPg (r-[KuPA-->K2HPgK3HPg]uPA), and K4HPgK5HPg (r-[KuPA- >K4HPgK5HPg]uPA). All of these variant genes, along with their wild-type (wt) r uPA counterparts, were expressed in human kidney 293 cells. In cases wherein EACA binding kringles from HPg have been placed in uPA, this property has been retained in the chimeric molecule and employed as an essential part of the purification procedures for the variants. The steady state amidolytic activity of two-chain (tc) wtr-uPA toward the chromogenic substrate, H-D-pyroglutamyl-Gly-L Arg-p-nitroanilide (S2444), is characterized by a kcat/KM (pH 7.4, 37 degrees C) of 120 s-1 mM-1. This value ranges from 92 s-1 mM-1 (tcr-[KuPA-->K1HPg]uPA) to 166 s-1 mM-1 (tcr-[KuPA-->K1HPgK4HPg]uPA) for each of the variants, demonstrating that the catalytic efficiency of the active site is altered only in a small way by changes in the noncatalytic domain of uPA. Small differences are also observed in the abilities of these tcr variants to interact with the fast-acting plasma inhibitor of uPA, viz., plasminogen activator inhibitor-1 (PAI-1). The second order rate constant for the interaction of PAI-1 with tcr-uPA, 0.46 x 10(7) M-1s 1 (pH 7.4, 10 degrees C), ranges from 0.29 x 10(7) M-1s-1 (tcr-[KuPA- >K1HPgK4HPg]uPA) to 1.08 x 10(7) M-1s-1 (tcr-[KuPA-->K4HPgK5HPg]uPA), for the tcr chimeric variants. Neither wtr-uPA nor any of its chimeric r-variants interacted macroscopically with a fibrin clot under conditions that allowed binding of 74% of single-chain r-tissue-type plasminogen activator. However, the tcr-chimeric uPA variants provided HPg-enriched clot lysis times between 0.2 (r-[KuPA- >K1HPgK4HPg]uPA) and 2.4 (r-[KuPA-->K2HPgK3HPg]uPA) relative to that of wtr uPA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8512312 TI - Cultured Ehrlich ascites tumor cells show increased N-linked alpha 2,6 sialyltransferase activity. AB - Ehrlich ascites tumor cells (EAT cells) are routinely grown in the peritoneal cavity of mice. These cells, EAT-wt, grow in suspension and exhibit a high level of alpha-2,3-O-linked sialyltransferase activity with benzyl-T-antigen (Gal beta 1,3Ga1NAc-alpha-O-CH2C6H5) as acceptor. These cells also contain a very low level of alpha-2,6-O-linked and alpha-2,6-N-linked sialyltransferase activity. A variant of these cells, EAT-c, has been selected to grow in cell culture, attached to the surface of culture flasks. EAT-c cells exhibit a selective increase of two- to fivefold in the activity of alpha-2,6-N-linked sialyltransferase activity, using asialo-alpha 1-acid glycoprotein as acceptor. Since a similar selective increase has been previously observed in metastatic human colorectal cancer tissues, the EAT-wt/EAT-c cell system may serve as a good experimental model for the investigation of sialyltransferases and their cell surface sialylated products in relation to cancer, metastasis, and cell-cell interaction. PMID- 8512313 TI - Hydroperoxide-induced diacylglycerol formation and protein kinase C activation in vascular endothelial cells. AB - We examined the effects of hydrogen peroxide (H2O2) and other hydroperoxides on endothelial cell protein kinase C (PKC) activity. Bovine pulmonary artery endothelial cells (BPAEC) were grown to confluent monolayers and PKC activity was determined in an in vitro assay by measuring phosphorylation of H1 histone. In control unstimulated BPAEC, PKC was primarily localized in the cytosol and treatment of BPAEC with H2O2 resulted in a concentration (10(-5) M-10(-3) M) and time (15 min-60 min.) dependent translocation of the enzyme from the cytosol to the membrane fraction. In addition to H2O2, linoleic acid hydroperoxide treatment of BPAEC also resulted in PKC activation while tert-butyl hydroperoxide and cumene hydroperoxide were not effective. In addition to causing an increase in membrane-associated PKC activity, H2O2 treatment also resulted in the partial loss of cytosolic PKC activity. As diacylglycerol (DAG) is a critical endogenous activator of PKC, we evaluated whether H2O2 exposure resulted in the increased production of DAG. Exposure to 1.0 mM H2O2 resulted in biphasic accumulation of DAG (two- to threefold). The first phase of DAG formation occurred within 5 min of H2O2 exposure while the second phase of accumulation began at 15 min of treatment and plateaued at about 45 min. The metal ions Cu2+ and Fe3+ augmented the H2O2-induced loss of total (cytosolic and particulate) PKC activity in BPAEC. These studies suggest that oxidants modulate PKC activity and increase DAG levels in vascular endothelial cells. PMID- 8512314 TI - Escherichia coli leader peptidase: production of an active form lacking a requirement for detergent and development of peptide substrates. AB - The report by Zimmermann et al. (J. Biol. Chem. 257, 1982, 6529-6536) that the active site of Escherichia coli leader peptidase (LPase) is located in the periplasm led us to explore the possibility that soluble, active short forms of LPase could be produced. Detergent-free delta 2-75 mutant protein (LPase-sf) lacking the two N-terminal transmembrane spanning and the cytoplasmic domains was produced in high yield. The mass of the protein determined by electrospray ionization mass spectrometry was 27,952 amu. The increase of 42 amu over that predicted by the expected amino acid sequence indicates that the N-terminus of LPase-sf is acetylated. This is consistent with the inability to obtain an N terminal sequence. LPase-sf lacks the site of autolysis present in LPase, thus circumventing problems associated with enzyme autocatalytic instability. LPase-sf and wild type LPase displayed comparable activity versus two peptide substrates. The peptides, based upon the cleavage sites of procoat and the precursor of maltose binding protein, were processed at the expected sites. In addition, the activity of both LPase's was not inhibited by classical inhibitors of the four classes of proteases. LPase-sf displayed similar activity in the presence and absence of detergent. Wild type LPase displayed specificity for alanine in the P1 subsite of the peptide WSASALX*KI and did not hydrolyze peptides with glycine, valine, or serine in that position. The availability of a detergent-free active form of LPase should facilitate mechanistic and structural studies. PMID- 8512315 TI - Inactivation of yeast hexokinase by Cibacron brilliant red 3B-A. AB - Procion or Cibacron blue dyes, containing polynuclear aromatic rings and mono- and dichlorotriazine nuclei, immobilized on dextran matrices, have been used for over a decade to purify diverse groups of enzymes by dye-ligand chromatography. Comparatively less attention has been paid to investigating the nature of molecular interactions between similarly constituted red dyes and various enzymes so as to ascertain their potential and thus justify their use in the purification of enzymes by dye-ligand chromatography. We investigated and found that Cibacron brilliant red 3B-A, a monochlorotriazine dye, inhibited phosphotransferase activity of yeast hexokinase. The dissociation constant, KD, and the rate of dye enzyme complex formation, k3, were 120 microM and 0.1 min-1, respectively. The enzyme was protected from inactivation by sugar and nucleotide substrates. About 2 mol of the dye bound per mole of the enzyme. The chromophore of the dye showed absorption at 524 nm. The visible difference spectrum of increasing concentration of the dye and same concentrations of the dye plus a fixed concentration of hexokinase exhibited a maximum, a minimum, and an isosbestic point at 569, 501, and 512 nm, respectively. The difference spectrum of the dye and dye in 60% ethylene glycol showed a maximum and a minimum at 556 and 495 nm, respectively. The dye showed no visible difference spectrum in the presence of hexokinase modified at the active site by iodoacetamide, pyridoxal phosphate, and o phthalaldehyde. Hexokinase modified by the dye coeluted with the unmodified enzyme during size-exclusion chromatography in the absence or presence of guanidinium hydrochloride. These results suggest that the dye interacts with the hydrophobic environment of the active site of the enzyme. Analysis of the kinetics of inhibition of hexokinase by model compounds and comparison of their computer-assisted three-dimensional representations with that of Cibacron brilliant red 3B-A suggest that 1-amino-8-naphthol-3,6-disulfonic acid may represent the minimum structure for the dye to bind. PMID- 8512316 TI - Calcyclin-binding site located on the NH2-terminal domain of rabbit CAP-50 (annexin XI): functional expression of CAP-50 in Escherichia coli. AB - CAP-50 (annexin XI) is a member of annexin family proteins originally identified and characterized as a target protein for calcyclin (H. Tokumitsu et al. (1992) J. Biol. Chem. 267, 8919-8924). In the present work, the calcyclin-binding site of CAP-50 was determined by proteolytic study and by using various deletion mutants expressed in Escherichia coli. The 43-kDa fragment of CAP-50 digested with Staphylococcus aureus V8 protease did not bind to calcyclin in the presence of Ca2+. CAP-50 fusion proteins, including various NH2-terminal deletion mutants were expressed in E. coli using rabbit CAP-50 cDNA and the calcyclin-binding potential was examined using the 125I-calcyclin gel overlay method and coprecipitation with phosphatidylserine-containing vesicles in the presence of Ca2+. All recombinant protein carried the potential for Ca(2+)-dependent phospholipid binding, due to the presence of the COOH-terminal domain (core domain). Calcyclin-binding experiments showed that CAP-50 molecules lacking the NH2-terminal 26 residues retain binding potential for calcyclin; however, deletion of an additional 26 amino acids from the NH2 terminus abolishes specific calcyclin binding. These observations suggest that the calcyclin-binding site is located on the NH2-terminal region of CAP-50, probably adjacent to or within the region from Tyr27 to Leu52. PMID- 8512317 TI - Inhibition of lung tissue oxidation during ischemia/reperfusion by 2 mercaptopropionylglycine. AB - The effect of 2-mercaptopropionylglycine (MPG), a potent free radical scavenger, on ischemia/reperfusion-induced tissue oxidation in isolated perfused rat lung was investigated. The isolated lung, continuously ventilated with 95% oxygen, was subjected to 1 h global ischemia followed by 1 h reperfusion with or without the presence of an antioxidant. In ischemic/reperfused lungs, there was a significant increase in protein oxidation (carbonyl formation) and lipid peroxidation (thiobarbituric acid reactive substances) to 10.7 nmol/mg protein and 176 pmol/mg protein, respectively, at the end of reperfusion. MPG administered at 6 mg/kg body wt intravenously to the rats prior to isolation of lung reduced protein oxidation by 65% and lipid peroxidation by 40%. An additional effect was noted when MPG was also added to the perfusate (0.275 mg/ml) during reperfusion. Pretreatment with dimethylthiourea (DMTU) or addition of desferal to the perfusate also significantly reduced the protein oxidation of lung ischemia/reperfusion. The addition of DMTU or desferal with MPG showed no additive effect. However, eicosatetraynoic acid (100 microM), a cyclooxygenase and lipoxygenase inhibitor, added with MPG reduced ischemia/reperfusion-induced lipid peroxidation by 80%, which was significantly greater than the protective effect exhibited by MPG alone. The oxidative stress on the lung tissue components was also demonstrated by a decrease in the sulfhydryl content of "end ischemic" lungs; MPG pretreatment maintained the sulfhydryl level at the control level in ischemic lungs. The results indicate that MPG at relatively low and non-toxic concentrations can markedly inhibit the oxidation of tissue sulfhydryls, soluble protein, and lipids associated with ischemia/reperfusion injury of the lung. PMID- 8512318 TI - Cytochrome P450 2B enzyme (CYP2B) induction defect following phenobarbital treatment in the fa/fa Zucker rat: molecular characterization. AB - The present study describes the mechanism of the dampened induction of the CYP2B1 and CYP2B2 genes following phenobarbital treatment in the phenotypically obese fa/fa Zucker rat. The fa/fa Zucker rat demonstrated a threefold lower level of CYP2B1/2B2 enzyme induction, as indicated by reduced testosterone oxidation at the 16 beta position and resorufin formation from pentoxy- and benzyloxyresorufin, protein concentration (Western blot analysis), and steady state mRNA levels (Northern and slot blot analyses) following in vivo treatment with phenobarbital than the Fa/? littermate controls. A primary hepatocyte cell culture system was used to determine if the dampened induction of the CYP2B1/2B2 enzyme is dependent on hormonal influences. Phenobarbital-treated (0.75 mM) hepatocytes from fa/fa Zucker rats showed approximately a three-fold lower induction response based on measurements of CYP2B1/2B2 (R-17 cDNA probe) and CYP2B1 (oligo probe) mRNAs. In order to evaluate whether this dampened response was at the level of transcriptional activation or initiation, as opposed to altered message stability, we measured the rate of transcription of CYP2B1/2B2 genes in nuclei from cultured hepatocytes during run-off experiments. Compared to Fa/? controls, the fa/fa Zucker rat had a greater than threefold lower nuclear transcription rate of CYP2B1/2B2 mRNA. These results suggest that the defective induction of the CYP2B1 and CYP2B2 genes exists at the transcriptional level in the mutant obese fa/fa Zucker rat. These data provide strong evidence that at least two genes are involved. Multiple gene involvement would suggest that the defect is not due to a mutation of the CYP2B gene cis-acting sequence. Instead, the lack of binding of a trans-acting factor, the presence of a repressor, or a defect in transcriptional activation is more likely the molecular mechanism(s) for this enzyme induction defect. PMID- 8512319 TI - Nitric oxide binding to human ferrihemoglobins cross-linked between either alpha or beta subunits. AB - We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the alpha chains with bis(3,5 dibromosalicyl) fumarate, and HbA-FMDA, modified between the beta chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of alpha and beta chains. The structural modifications result in altered rate constants for NO binding to both alpha and beta chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity. PMID- 8512320 TI - Molecular diversity of calpastatin in human erythroid cells. AB - According to differences in mobility on SDS-polyacrylamide gel electrophoresis, calpastatins (inhibitor proteins of the calcium-dependent proteinase calpain) are classified into the tissue type (100-120 kDa) and the erythrocyte type (70 kDa), which lacks the amino-terminal domains (domains L and 1). We investigated the molecular diversity of calpastatin in human hematopoietic cells by Western-blot analysis and by the reverse-transcription-polymerase-chain reaction method. While the mononuclear and polymorphonuclear cells in peripheral blood showed the tissue type (110 and 114 kDa), a cell line of erythroid cells (JK-1) showed both the tissue type (110 kDa) and the erythrocyte type (70 kDa) at approximately equal ratios. When the lysate of JK-1 cells was incubated in the presence of ATP, the 110-kDa form was degraded much faster than the 70-kDa form. In human erythrocytes, the 110-kDa form was identified as the tissue type by an antibody recognizing domain L, and this form was also present in addition to the predominant 70-kDA form. JK-1 cells, as well as nucleated cells in peripheral blood, contained calpastatin mRNA with exon-3-deleted. Glioblastoma and fibroblast cell lines expressed the nondeleted calpastatin mRNA in addition to the deletion type, and they showed bands corresponding to 117 kDa as well as 110 and 114 kDa. The 117-kDa band was detectable by an anti-exon 3 peptide antibody. These results suggest that diversity among the tissue type calpastatins is caused by both alternative splicing and post-translational processing whereas the apparent conversion from the tissue type to the erythrocyte type is caused by proteolytic processing. PMID- 8512321 TI - A novel polymorphism of human serum amyloid A protein, SAA1 gamma, is characterized by alanines at both residues 52 and 57. AB - We have identified a hitherto unknown polymorphism of serum amyloid A protein (SAA) in the pooled serum of nonamyloidotic inflammatory patients. The molecular weight of the novel SAA determined by ion-spray mass spectrometry appeared 28 amu lower in mass than the known SAA1 subsets, indicating that the substitution of a valine residue by an alanine was present. Further analyses by the combination of liquid chromatography/fast atom bombardment mass spectrometry, collision activated dissociation mass spectrometry, and amino acid analysis revealed that this novel SAA, designated SAA1 gamma, has alanines at both residues 52 and 57 while the two known SAA1 subsets have a valine at either residue 52 or 57. Furthermore, des-1 Arg and des-1 Arg-2Ser forms of SAA1 gamma as well as those of the known SAA1 subsets were identified. This indicated that the common modification must have occurred at the N-termini of all SAA1 subsets. The existence of this SAA1 gamma had been suggested from one of the two novel AA proteins that we recently found (Baba, S. et al., 1992, Biochim. Biophys. Acta, 1180, 195-200). PMID- 8512322 TI - The serine protease inhibitor family from Ascaris suum: chemical determination of the five disulfide bridges. AB - Chymotrypsin/elastase inhibitor-1 is a member of the Ascaris family of serine protease inhibitors. It is characterized by five disulfide bridges in a polypeptide chain of 63 amino acids. The disulfide bridge pairing was resolved by cleavage at methionyl residues with cyanogen bromide followed by a combination of proteolytic digestions with glycyl endopeptidase, Staphylococcal serine proteinase, and submandibular proteinase A. The peptides were separated on a reverse-phase HPLC column. Amino acid analyses and N-terminal microsequencing of the cystine containing peptides revealed the disulfide bridge pairing between residues 5-54, 15-29, 18-38, 22-33, and 40-60. The disulfide bridge pairing of other members of this unique family was also assigned. The major isoform, trypsin inhibitor-1, and chymotrypsin/elastase inhibitor-4 share the same disulfide bridge pattern. These results strongly suggest that all members of the Ascaris family of serine protease inhibitors have the same disulfide bridge pattern which represents a unique motif. PMID- 8512323 TI - The structure of two murine class-mu glutathione transferase genes coordinately induced by butylated hydroxyanisole. AB - We report the sequences of two coordinately induced murine glutathione transferase genes, mGSTM1 (GT8.7, Yb1) and mGSTM3 (GT9.3). Genomic clones covering the entire mGSTM1 gene were isolated; comparison of the mGSTM1 gene with genomic sequences from rat class-mu glutathione transferase genes suggests that the mGSTM1 gene is orthologous to the rGSTM1 (rat3, Yb1) gene. The start of mGSTM1 mRNA transcription was mapped by primer extension and RNase protection to 37 nucleotides upstream from the initiation codon. The 160 nucleotides 5' proximal to the start of transcription match exactly the 5'-end of the class-mu glutathione transferase cDNA clone pmGT10. An mRNA transcript was found approximately 2.0 kb upstream from the start of mGSTM1 transcription; its sequence does not show significant similarity to other sequences in the DNA or protein sequence databases. The mGSTM1 gene contains a TATAAA sequence at -31 nucleotides upstream from the start of transcription, but no exact match to the antioxidant response element (RGTGACNNNGC), the xenobiotic response element (TNGCGTG), or the AP-1 consensus (TGASTMA) is found in the 5'-flanking region, although near matches are found in the 5'-flanking region, in intron 1, and in other parts of the gene. A genomic clone containing the first five exons of the mGSTM3 gene was also isolated. The mGSTM3 gene contains several repetitive elements--two upstream from the start of transcription and one within intron 2- that disrupt its similarity with the mGSTM1 gene. The 5'-flanking sequence of the mGSTM3 gene does not contain a TATAAA sequence or any exact matches to ARE or XRE consensus sequences, although an Sp1 binding site is found at -66. mGSTM3 and mGSTM1 diverge substantially outside their exons and share less than 60% sequence identity in the 5'-flanking region. Thus, it is likely that the mGSTM1-mGSTM3 gene duplication predates the rat-mouse divergence. The strongest region of conservation between the mGSTM1 gene and the mGSTM3 gene occurs in exon 3, intron 3, and exon 4; this region also shares strong similarity with the rGSTM1 (rat3, Yb1) and rGSTM2 (rat4, Yb2) genes. PMID- 8512324 TI - The inhibition of trypsin and alpha-chymotrypsin proteolytic activity by aluminum(III). AB - In Alzheimer's disease, among different hypotheses, amyloid is thought to be formed from a disequilibrium between proteases and protease inhibitors with a consequent production of self-aggregating fragments that are deposited in brain tissues. In this paper we present evidences that aluminum(III) can be a candidate for playing a dismetabolic role in inhibiting the proteolytic activity of the serine proteases trypsin and alpha-chymotrypsin, and the inhibitory reaction can be reversible in the presence of EDTA. The relevance of the physicochemical properties of the metal coordination sphere in this inhibitory effect is also discussed. PMID- 8512325 TI - Isolation by a new method and sequence analysis of chromosomal HMG-17 protein from porcine thymus. AB - Nonhistone chromosomal protein HMG-17 from porcine thymus has been isolated by extraction in boiling water, gel filtration and HPLC, and its complete primary structure (89 residues) has been determined. Peptides derived from enzymatic hydrolysis with trypsin, Staphylococcus aureus V-8 protease, Arg-C, and Glu-C proteinases were purified by HPLC and sequenced by the 4-(N,N dimethylamino)azobenzene-4'-isothiocyanate/phenylisothiocyanate double coupling method. Porcine HMG-17 has a molecular mass of 9248 Da and a pI > 9.8. No glycosylation or methylation has been detected. The primary structure of this protein is almost identical to the sequence deduced from a cDNA clone derived from a human cell line. Porcine thymus HMG-17 differs from the human protein by only a single conservative substitution at position 64 (aspartic acid instead of glutamic acid). As in other HMG-17 proteins, the sequence is characterized by a lysine- and proline-rich central region, which has been implicated in DNA binding. PMID- 8512326 TI - Factors affecting the species-homologous and species-heterologous binding of mitochondrial ATPase inhibitor, IF1, to the mitochondrial ATPase of slow and fast heart-rate hearts. AB - We examined the effects of a variety of conditions upon the IF1-mediated inhibition of the ATPase in both intact and sonicated mitochondria and in IF1 depleted submitochondrial particles (SMP) in species-homologous and species heterologous combinations of IF1 and ATPase. IF1-mediated ATPase inhibition occurred in intact rabbit heart mitochondria at low matrix pH and low membrane potential, but not in intact pigeon and rat heart mitochondria under the same conditions. IF1-mediated ATPase inhibition was, however, demonstrable in both the rabbit and pigeon heart systems in sonicated mitochondria incubated at low ionic strength. The rat heart system failed to exhibit significant IF1-mediated ATPase inhibition in either intact or sonicated mitochondria due to the low amount of IF1 present. When rabbit heart IF1-containing extracts were incubated with IF1 depleted rabbit heart SMP over a range of KCl concentrations, increasing the [KCl] to 100 mM had little effect on IF1-mediated ATPase inhibition. When pigeon heart IF1-containing extracts were incubated with IF1-depleted pigeon heart SMP under the same conditions, increasing [KCl] to 100 mM nearly completely blocked IF1-mediated ATPase inhibition. While the species-endogenous level of rat heart IF1 (i.e., 1x IF1) inhibited IF1-depleted rat heart SMP virtually not at all at any [KCl] examined, the 8x rat heart IF1 was nearly as inhibitory as the 1x rabbit heart IF1 at varying ionic strengths. When rabbit, pigeon, or rat heart IF1 was bound to rabbit versus pigeon IF1-depleted SMP, the effect of varying ionic strength on IF1-mediated ATPase inhibition was related to the species source of the IF1, not to the species source of the enzyme; 1x bovine heart IF1 purified to homogeneity behaved much like 1x crude rabbit heart IF1 when binding to either the rabbit or the pigeon heart enzyme. This suggests that an IF1-ATPase complex stabilizing factor such as has been isolated from baker's yeast cells in neither lacking in the pigeon heart system nor required for the more ionic strength-resistant binding of IF1 observed in slow heart-rate mammalian heart mitochondria. PMID- 8512328 TI - Separation of freezing- and drying-induced denaturation of lyophilized proteins using stress-specific stabilization. I. Enzyme activity and calorimetric studies. AB - Stabilization of labile proteins during lyophilization requires protection of the protein against both freezing and dehydration stresses. Solutions of 1-10% (wt/vol) polyethylene glycol (PEG) fully protected both lactate dehydrogenase and phosphofructokinase during freezing and thawing, but did not stabilize the proteins during freeze-drying. Thus, with this lyophilization system a second compound could be tested for its capacity to stabilize dried proteins, independent of its ability to provide cryopreservation. In the presence of low concentrations of glucose or trehalose (which alone provided minimal protection) and 1% PEG (wt/vol), almost full enzyme activity was recovered after freeze drying and rehydration. Differential scanning calorimetry indicated that the PEG was crystalline and the sugars were amorphous in the dried samples. Experiments with lactose and mannitol demonstrated that if these compounds also crystallized during freeze-drying, protein stabilization was reduced or abolished. PEG stabilizes the proteins during freezing, due to preferential exclusion of PEG from the protein's surface. The sugars protect the proteins during dehydration by hydrogen bonding to the dried protein, thus serving as water substitutes. This report provides the first example of stabilization of proteins during lyophilization through separate, specific treatments of the fundamentally different stresses of freezing and dehydration. PMID- 8512327 TI - Relationship between iron and phosphate in mammalian ferritins. AB - The core of mammalian ferritin is known to contain varying amounts of phosphate as well as iron. This study examined the variations in phosphate found in ferritins from horse spleen, rat liver, and bovine liver. The amount of phosphate varied inversely with the amount of iron present in the core. Theoretical extrapolation showed that in the absence of phosphate approximately 4400 atoms of iron could be incorporated into ferritin. Reconstitution of ferritin with iron and ceruloplasmin followed by prolonged incubation with phosphate produced cores similar to native ferritin in terms of iron to phosphate ratios and rates of iron release. However, ferritin reconstituted in the presence of phosphate differed markedly from native ferritins. The data suggest that phosphate is an integral part of mammalian ferritin cores and influences both core formation and the ease by which iron is released from ferritin. PMID- 8512329 TI - Separation of freezing- and drying-induced denaturation of lyophilized proteins using stress-specific stabilization. II. Structural studies using infrared spectroscopy. AB - The conformation of two labile enzymes, lactate dehydrogenase and phosphofructokinase, has been examined in the aqueous and lyophilized states, using infrared spectroscopy. In the preceding paper it was demonstrated that a stress-specific stabilization scheme, which employs a combination of a cryoprotectant (polyethylene glycol) and a compound which protects the dried protein (sugars or mannitol), can be used to optimize recovery of activity of these enzymes upon freeze-drying and rehydration. The purpose of the present study is to determine the effects of these additives on the conformation of these enzymes during lyophilization. Lyophilization in the absence of stabilizers was observed to induce significant conformational changes in both enzymes. Addition of 10 mM mannitol, lactose, or trehalose or 1% polyethylene glycol to the enzyme solutions attenuated the unfolding, but significant spectral differences for the enzymes in the dried state are still observed when compared to the aqueous conformation. Addition of any one of these stabilizers does not improve recovery of activity. However, when a combination of 1% PEG and either 10 mM mannitol, lactose, or trehalose is added, the native structure is preserved during lyophilization and essentially full enzymatic activity is recovered upon reconstitution. The ability of the stabilizers to preserve the native structure during lyophilization correlates directly with the recovery of enzymatic activity upon reconstitution. It appears that for labile proteins, preservation of the native structure during lyophilization is requisite for recovery of activity following rehydration. This study demonstrates that the infrared spectroscopic technique is a rapid and useful method for studying protein conformation in the dried state and can aid in determining the optimal conditions for stabilization of proteins during lyophilization. PMID- 8512330 TI - Nicotinamide ribose 5'-O-[S-(3-bromo-2-oxopropyl)]thiophosphate: a new affinity label for NMN sites in enzymes. PMID- 8512331 TI - [Development of differentiation therapy]. PMID- 8512332 TI - [Treatment results of intra-arterial ACNU infusion chemotherapy for primary cerebral malignant lymphoma]. AB - From May, 1987 to January, 1991, eight patients harboring primary cerebral malignant lymphoma (primary, six cases; recurrent, two cases) were treated by intra-arterial ACNU infusion chemotherapy. All but two cases also had hyperosmotic blood brain barrier (BBB) modification. Six primary cases had conventional teletherapy of 46-58.7 Gy (average 54.1 Gy) and one recurrent case had been irradiated again by 18 Gy. The follow-up period was 3 to 67.5 months (average 21.4 months). In six cases demonstrating measurable tumors on diagnostic images, all showed a complete response. The 1- and 2-year survival time was 50.0% and 37.5%, respectively, with a median survival time of 13.0 months. These were somewhat better than our previous results, but not better than those in the literature. Although intra-arterial ACNU infusion chemotherapy with BBB modification was not considered superior to other chemotherapy regimens, it yielded some long-surviving cases. Hence this chemotherapy is still worth using for treatment of primary cerebral malignant lymphoma. PMID- 8512333 TI - [A case report: multiple liver metastasis of gastric cancer responding to intraarterial infusion of MTX and 5-FU]. AB - In a 63-year-old male patient with gastric cancer having multiple liver metastases, the metastatic lesions responded well to postoperative staggered intraarterial infusion therapy with MTX and 5-FU. The intraarterial infusion therapy was administered once a week. A total of 5 courses of this therapy produced marked regression of liver metastases and remarkable necrosis. The effect was thus rated as PR. The patient is healthy and has been successfully rehabilitated. His dose is oral 5-FU (200 mg x 2). PMID- 8512334 TI - [A patient with stage IV gastric cancer responding to combination chemotherapy with 5-FU, leucovorin and CDDP]. AB - The patient was a 44-year-old male with gastric cancer accompanied by pancreatic invasion and metastasis to the periaortic lymph nodes. Combination chemotherapy with 5-FU, leucovorin (LCV) and CDDP (FLP therapy) was preoperatively given. Pancreaticoduodenectomy was carried out as absolutely noncurative resection. FLP therapy was continued postoperatively, and resulted in disappearance of the metastases in the periaortic lymph nodes on CT. As there were no findings of recurrence, the patient was regarded as being in complete response. In addition, the performance status improved from Grade 2 to Grade 0. Since the three-drug combination therapy induced only slight adverse reactions (Grades 1-2), it could be safely carried out at the outpatient department. Thus, combination therapy with 5-FU, LCV and CDDP is thought to be effective against gastric cancer. PMID- 8512335 TI - [A case of recurrent colon cancer treated markedly effective with 5'-DFUR]. AB - A 71-year-old male with recurrent colon cancer was admitted to our hospital with obstructive jaundice. Virchow's node metastasis was palpable in his neck. The enlarged intraabdominal lymphnodes due to recurrence and liver metastasis were demonstrated on computed tomography. Bile duct obstruction was treated by expandable metallic biliary endoprosthesis. 5'-DFUR (5'-deoxy-5-fluorouridine) was administered orally at 600 mg daily. Virchow's node metastasis completely disappeared by 46 days after administration of 5'-DFUR. The enlarged intraabdominal lymphnodes and liver metastasis disappeared on computed tomography. No significant side effects from 5'-DFUR were encountered for 18 months. 5'-DFUR appears to be a useful and safe treatment for recurrent colon cancer. PMID- 8512336 TI - [A case of giant advanced breast cancer responding remarkably to CEFT therapy]. AB - A fifty-two-year-old female was admitted with unresectable advanced giant breast cancer, which was attached to the chest wall and had a bone metastasis to the thoracic vertebrae. At first, depression and fixation were performed for the bone metastasis, and 2 courses of CEFT therapy were administered. One course was intra arterial chemotherapy. After 2 courses of treatment, the tumor size was not changed, but tumor marker, CT and physical findings showed a remarkable improvement, and mastectomy could be performed. It was suggested that this regimen is very effective for advanced giant breast cancer. PMID- 8512337 TI - [A case of complete response was achieved with arterial infusion chemotherapy including CDDP, etoposide and pirarubicin]. AB - A 67-year-old man was admitted with the chief complaint of macroscopic hematuria in May 1990. Endoscopic examination showed a bladder tumor at the right lateral wall. Biopsy proved Grade 3 transitional cell carcinoma. Transurethral ultrasonogram, CT scan and MRI revealed T2-T3a invasive bladder cancer. Preoperative chemotherapy by balloon occluded arterial infusion using CDDP 75 mg, etoposide 100 mg and pirarubicin 50mg was performed. Repeat endoscopy after chemotherapy revealed significant necrotic change of tumor. Radical cystectomy and pelvic node dissection with ileal conduit urinary diversion were performed in August 1990. Significant necrosis of bladder wall was observed and no cancer cells were recognized in the cystectomy specimen. The patient is alive at this writing with no evidence of disease for 2 years. PMID- 8512338 TI - [Chronic daily oral low-dose etoposide therapy for an aged patient with aggressive lymphoma: a successful case report]. AB - A 72-year-old female from Fukuoka Prefecture was admitted to our hospital complaining of puffy face and general malaise in April, 1992. Physical examinations revealed generalized lymphadenopathy and hepatosplenomegaly complicated with superior vena cava syndrome. A histological diagnosis of diffuse large cell-type malignant lymphoma was made by cervical lymph node biopsy according to the Working Formulation. Immunohistochemical staining showed the lymphoma cells were of T cell lineage (CD43+). Though anti-human T lymphotropic virus type I (HTLV-I) antibody was positive, southern blot analysis of the cells did not reveal monoclonal integration of HTLV-I proviral DNA. Her liver and renal function were almost normal but there was slight elevation of LDH. Considering her age, oral administration of low-dose etoposide (25 mg/day) was started. In 4 days, her lymph nodes decreased in size with subjective improvements. Ten weeks later, examinations of the hand, ultrasonogram and CT scan showed lymphadenopathy and hepatosplenomegaly had disappeared completely. The neutrophil count was consistently above 1,500/microliters, with no remarkable adverse effects and only a moderate degree of alopecia. Thus, low-dose etoposide therapy was considered to be very useful in such a case of malignant lymphoma in the elderly. PMID- 8512339 TI - [Study on three patients with malignant glioma showing tumor reduction during maintenance therapy with MCNU]. AB - Tumor regression occurred in three of 19 patients (15.8%) with malignant glioma during maintenance therapy using MCNU. In two patients, the tumor reduced 5 and 8 months after the initial treatment, respectively. In the remaining patient, though the maintenance therapy was interrupted for a while and consequently the tumor size increased, readministration of MCNU reduced the tumor size two months later. Therefore, since the antitumor activity of MCNU against malignant glioma seems to require a certain time depending on the case, it is recommended that MCNU be given as maintenance therapy for at least half a year. PMID- 8512340 TI - [Intraperitoneal 99mTc infusion for assessment of intraperitoneal fluid dynamics]. PMID- 8512341 TI - [Bovine endothelial cell destruction by choriocarcinoma cell line (SMT-cc1) (inhibition of destruction by urinary trypsin inhibitor)]. PMID- 8512342 TI - [Ras p21 and signal transduction]. AB - It is known that ras gene was discovered as a transforming gene of rat sarcoma virus. This gene is conserved ubiquitously from yeast to human, and a dominant activating mutation of ras results in transformation in mammalian cells. Currently it is evident that ras gene regulates cell proliferation and differentiation. The gene product, ras p21, binds to GDP or GTP, and hydrolyzes GTP to GDP and Pi. The GTP-bound form is in active conformation which transmits signals to a downstream target. In this review, we focus on how the activity of ras p21 is regulated and on the mode of action of ras p21 in cell proliferation and differentiation. PMID- 8512343 TI - [Cancer cells and apoptosis]. PMID- 8512344 TI - Attitude towards serological tests for infection during pregnancy. AB - In anticipation of systematic prenatal screening at the antenatal clinic of Gasthuisberg University Hospital, Leuven, Belgium, the attitude of 500 successive pregnant women towards testing for rubella, toxoplasmosis, hepatitis B virus, HIV and syphilis was studied by means of written questionnaires. All tests were well accepted, toxoplasmosis and rubella being most (92 and 91%), syphilis and HIV being least (79 and 82%) favoured. Refusal was generally associated with lower education, but refusal for syphilis and HIV was associated with high education. Ninety-four percent wanted to be informed of the results of the tests. Only one woman (0.2%) of those who agreed with testing did not want to know her HIV test result. Pregnant doctors were more reluctant about screening, in particular for sexually transmitted diseases, whereas nurses were in favour of it. Written information failed to increase the acceptance rate, but lowered the number of women without an opinion. PMID- 8512345 TI - Expression of epidermal growth factor receptor (proto-oncogene c-erbB-1) and estrogen receptor in human breast carcinoma. An immunocytochemical study of 70 cases. AB - In vitro studies have shown that growth factors may mediate the growth stimulatory effect of estrogen in hormone-dependent human breast carcinomas while the constitutive expression of same growth factors might by-pass the need for estrogenic stimulus in hormone-independent neoplasms. We have performed immunocytochemical analysis of the expression of epidermal growth factor receptor (EGF-R or proto-oncogen c-erbB-1) and estrogen receptor (ER) in 70 cases of human breast carcinoma. We found an inverse relationship between the expression of EGF R and ER (Kendall's tau b = -0.1997, P < 0.03), which prompts us to conclude that ER(-) breast carcinomas may grow in a hormone-independent manner through the over expression of the proto-oncogene c-erbB-1, which is the receptor for epidermal (EGF) and alpha transforming (TGFalfa) growth factors. PMID- 8512346 TI - Hexoprenaline activates potassium channels of human myometrial myocytes. AB - Hexoprenaline is a beta-adrenergic agent used for tocolysis after the 26th week of pregnancy. The purpose of the present study was to demonstrate the site of action of hexoprenaline on the membrane of single isolated smooth muscle cells. The main action of beta-mimetics on the cell is hyperpolarization of the cellular membrane, i.e. beta-mimetics have similar effects as K(+)-ions (Standen et al., 1989). Our results indicate a prolonged and significantly enhanced activity of K(+)-channels in the cell membrane, as may also be demonstrated by the use of the K(+)-channel activator Calcitonin-gene related peptide (CGRP). In control experiments under physiological conditions, we observed a large conductance K(+) channel with 158 pS. The channel was voltage dependent and Ca++ sensitive indicating that it belongs to the class of big conductance Ca(++)-activated K(+) channels (BKCa). Hexoprenaline and CGRP both increased the open probability (P(o)) of the channel measured with the patch clamp system in the cell attached configuration. Hexoprenaline was also an activator of the BKCa in the presence of Nitrendipine, indicating that the activation of the Ca++ sensitive channel is not an indirect effect of Ca++ currents via L-type Ca++ channels. PMID- 8512347 TI - Maternal serum CA125 levels in early intrauterine and tubal pregnancies. AB - Using an immunoradiometric assay, serum CA125 levels were measured in 13 women with a normal pregnancy, 9 with a spontaneous abortion, 3 with a hydatidiform mole, and 15 with a tubal pregnancy. Serum CA125 levels were high in patients with a normal pregnancy (154 +/- 169 U/ml; mean +/- S.D.), a spontaneous abortion (244 +/- 258 U/ml), or a hydatidiform mole (54 +/- 16 U/ml). In contrast, CA125 levels in patients with a tubal pregnancy (33 +/- 25 U/ml) were low, and almost all of those without uterine bleeding (25 +/- 9 U/ml) were within the normal range for non-pregnant women (< 35 U/ml). The difference between serum CA125 levels with intrauterine pregnancy and with tubal pregnancy may be ascribed to the difference of the amount of decidual tissues at the site of trophoblastic invasion. PMID- 8512348 TI - Study of two simplified microsurgical techniques for uterine horn anastomosis in rat. AB - This study compares two simplified techniques, which use only 2 and 4 sutures respectively, with a conventional technique with 8 sutures for fallopian tube anastomosis. Experimentally these techniques were performed on the uterine horns of fifteen female rats. A 100% patency rate was obtained with all three techniques. No difference in the mucosal, muscular and serosal regeneration was observed in the three groups at 10, 20 and 60 days. Two months after surgery, the serosa, muscularis and mucosal layers were completely continuous in all groups. The operating with 2 sutures (5'30" +/- 1'10") was significantly less than with 4 (9'09" +/- 0'55", P < 0.05 ANOVA) and 8 sutures (15'12" +/- 1'41", P < 0.05 ANOVA). A minimum inflammatory reaction to sutures was observed in all three groups at 60 days after surgery. The results suggest that with 2 sutures are all that is needed for tissue repair. PMID- 8512349 TI - Accuracy of bimanual palpation versus vaginosonography in determination of the measurements of pelvic tumors. AB - In a prospective study the size of 157 pelvic tumors in 101 patients was measured preoperatively by bimanual palpation and vaginosonography, and the results were compared with measurements made at operation. In 72 uterine and 85 ovarian lesions the Spearman correlation coefficients (rs) between the three maximum diameters at right angles to each other measured at operation and by bimanual palpation ranged from 0.48 to 0.78. The correlation coefficients (rs) between measurements at operation and preoperative vaginosonography ranged from 0.91 to 0.97. The size of small lesions was overestimated by bimanual palpation; 44% of tumors smaller than 5 cm in diameter were only detected by vaginosonography. PMID- 8512350 TI - Maternal mortality in southern Israel. AB - Between 1969 and 1991 there were 166,410 births in Southern Israel with 13 maternal deaths (7.8/100,000). In the Jewish population there were 119,130 deliveries with 7 maternal deaths (5.9/100,000), and the Bedouins had 47,280 deliveries with 6 maternal deaths (12.7/100,000). Prenatal care was an important preventive factor. 7 maternal deaths occurred among 151,088 women who had received prenatal care (4.6/100,000), whereas 6 such deaths occurred among 15,322 without prenatal care (39.1/100,000) (P value 0.0005). Ten of the 13 women who died were over 24 years old. Eight of the 13 patients were multiparous. Live births occurred in 6 patients and stillbirths in 5 patients. Hemorrhage, preeclampsia-eclampsia and pulmonary embolism were the leading causes of maternal death. PMID- 8512352 TI - [My endoscopic surgery learning (United States--1946)]. PMID- 8512351 TI - Primary ovarian lymphoma. A case report. AB - A 44-year-old woman with stage IV non-Hodgkin's lymphoma (NHL) of the left ovary is described. She had an extended hysterectomy and bilateral salpingo-ophorectomy and thereafter received six courses of combination chemotherapy (cyclophosphamide, adriamycin, vincristine and predonisolone; CHOP). The patient is well with no evidence of recurrence at 12 months after surgery. The literature on primary ovarian lymphoma is reviewed. PMID- 8512353 TI - [Fournier's gangrene. Presentation of 11 cases and review of the literature]. AB - Fournier's gangrene is an infectious necrotizing cellulitis of the penis and/or perineoscrotal region, which rapidly progresses and carries a high mortality. Eleven cases of Fournier's gangrene that had undergone an emergency procedure from 1985 to 1992 are described. Excellent results were achieved, with a survival rate of 91%. In our view, treatment of this disease entity is fundamentally based on early diagnosis, wide radical debridement of the affected area, frequent local treatment, debridement at the least sign of recurrence and early antibiotic therapy with three agents. PMID- 8512354 TI - [Basic concepts in the use of tumor markers in the diagnosis and follow-up of malignant bladder neoplasms]. AB - The absence of reliable diagnostic elements for the evaluation of malignant bladder tumors and the low sensitivity of the conventional diagnostic methods have prompted studies on the biological behaviour of this tumor type. The well known studies of Gold and Freedman and the recent investigations of Bates and Logo have proposed using tumor markers for early diagnosis and follow-up of different types of malignant tumors. However, the "ideal" tumor marker, one that is sufficiently sensitive and specific, has as yet to be discovered. We reviewed the tumor markers widely utilized to diagnose and follow-up malignant bladder tumors, and describe their main features. It must be pointed out that the lack of sensitivity and specificity of these tumor markers have led to the development of a new generation of tumor markers, such as cytogenetic markers, oncogenes, etc. Undoubtedly, this review of the literature will become obsolete with the advent of subsequent generations of tumor markers. PMID- 8512355 TI - [Renal sarcomatoid carcinoma. Report of 9 cases]. AB - We reviewed 9 cases of sarcomatoid carcinoma of the kidney from 233 cases of renal carcinoma that had undergone surgery over a period of 21 years (1970-1991). The principal characteristics (patient age, sex, diameter, clinical features, stage, grade, mitotic index, radiological features) were analyzed and compared with the rest of the series. This histological type is distinct from other types of renal carcinoma in that it carries a poor prognosis (with a mean survival of 6 months), it is usually diagnosed in the advanced stages, with a high mitotic index and tumor grade. It presents no special clinical and radiological features which make it distinct from the other histological types of renal carcinoma. PMID- 8512356 TI - [Carcinoma of the penis: our experience in 24 cases and review of the literature]. AB - Squamous cell carcinoma of the penis has a very scant incidence in our setting and evolves slowly. From 1978 to 1991, 24 cases of penile carcinoma had been treated and followed at our service. The results achieved with partial amputation of the penis have been highly satisfactory for stages T1 and T2, which was combined with postoperative radiotherapy for the latter tumor stage. Since carcinoma of the penis generally presents with infection, if lymphadenectomy is performed, it has to be performed after the amputation. The peculiar features of this disease, patient characteristics and the diversity of the therapeutical approaches make penile carcinoma a lesion whose treatment is controversial and, in many cases, difficult to follow. PMID- 8512357 TI - [True post-micturition urinary incontinence of the male]. AB - Herein we describe 3 cases of male urinary incontinence that had consulted for intense dribbling at the end of voiding. The urodynamic study identified the true postmicturition urinary incontinence in the male, whose origin was ascribed to alterations in the terminal phase of voiding, arising from localized disorders in the posterior or anterior urethra. The major significance of the true postmicturition urinary incontinence in the male lies in the need to distinguish it from other types of urinary incontinence with more clinical importance. PMID- 8512358 TI - [Impotence caused by venous leakage: surgical treatment. Short- and mid-term results]. AB - We reviewed the results achieved by ligation of the deep dorsal vein of the penis in 14 males with erectile dysfunction secondary to venous leakage. Prostaglandin E1 injection, echo Doppler and cavernosometry were utilized for the diagnosis. Surgical correction was performed when the cavernosometric flow required for erection was more than 200 cc/minute. The patients had a follow-up evaluation at 3, 6 and 12 months postoperatively. At one year, 4 (28.5%) patients showed good results and 10 (71.4%) poor. The factors that may influence the short, medium and long-term results are briefly described. PMID- 8512359 TI - [Laparoscopic signs of testicular absence]. AB - Unlike the other exploratory techniques (US, arteriography, phlebography, CT and MRI), laparoscopy constitutes the only reliable diagnostic method for absent testis, which has a high incidence in children with non palpable testes. The finding of the blind-ending spermatic veins and deferent duct confirms the diagnosis of absent testis. PMID- 8512360 TI - [Neurogenic bladder and recurrent emphysematous cystitis]. AB - A case of recurrent emphysematous cystitis in a 44-year-old male diabetic is described. Treatment of the first episode had been effective and demonstrable radiologically. A recurrent episode of cystitis disclosed a neurogenic bladder, which had not been detected previously. The literature on the pathogenesis of this entity is briefly reviewed. PMID- 8512361 TI - [Ureteral obstruction secondary to intrapelvic migration of methyl methacrylate following total hip replacement]. AB - We report an uncommon case of ureteral obstruction arising from the cement utilized to fix a total hip prosthesis. The pathophysiological mechanisms that may cause urinary tract involvement in this type of surgery are discussed. PMID- 8512362 TI - [Acute abdomen, as diagnostic cause of renal adenocarcinoma]. AB - We report a case of renal adenocarcinoma that was diagnosed after an emergency nephrectomy procedure. The patient had presented with a typical acute abdomen. The diagnostic methods and treatment are briefly discussed. The uncommon form of presentation (renal adenocarcinoma coexisting with multiple renal abscesses presenting as acute abdomen) prompted us to report this case. PMID- 8512363 TI - [Giant retroperitoneal liposarcoma]. AB - A case of giant retroperitoneal liposarcoma is described. Treatment was by radical surgery, using the anterior approach, with preservation of the renal unit. The diagnostic procedure is briefly discussed and the literature reviewed. PMID- 8512364 TI - [Diagnosis of renal vein and inferior vena cava thrombosis: report of a new case]. AB - Renal vein thrombosis is a rare pathology whose diagnosis entails difficulty. A case of renal vein and inferior vena cava thrombosis is described herein. We briefly discuss its association with the nephrotic syndrome, the diagnostic methods and therapeutic approaches. PMID- 8512365 TI - [Multilocular cystic renal adenocarcinoma]. AB - On detecting a complex cystic renal mass, we are faced with the problem of making the differential diagnosis from a variety of diseases, some of very distinct nature and prognosis. Surgical exploration may occasionally be warranted to make the diagnosis since no radiological or analytical method, including cytological analysis of its content, is absolutely reliable. A 46-year-old male patient with multicystic renal adenocarcinoma is described. We discuss the diagnostic and therapeutic dilemmas that arise on detecting a multilocular renal mass in an adult patient. PMID- 8512367 TI - Continent diversion vesicoplasty for the treatment of the irreparable, multi operated urethral stricture patient. AB - A continent diversion vesicoplasty technique has been developed for patients with irreparable lower urinary tract secondary to severe urethral trauma and subsequent deleterious iatrogenic effects. Five cases were treated in which at least ten urethral repair attempts were previously performed. All patients were younger than 30 years old and have been in urological consultation for more than ten years. The surgical technique involves a non-detubularized ileocecal segment with a stapled stabilized intussuscepted nipple, that combines the experience gained with intestinal segments in either benign, malignant or congenital disease. The most important details of each technique have been utilized and are accurately explained. All patients have been restored to a fairly normal life. These cases represent a group of otherwise healthy young individuals with an extremely incapacitating benign disorder. PMID- 8512366 TI - [Bladder inverted papilloma. Can it be considered as a neoplasm with low degree of malignancy?]. AB - We report a case of inverted papilloma of the bladder. The clinical features, diagnosis and treatment of this tumor type are discussed. We underscore the histology and histogenesis of the two types: trabecular inverted papilloma and glandular inverted papilloma. A review of the literature has shown that inverted papillomas do not show clinical or histological features of malignancy most of the time. The cases with synchronous or metachronous association with transitional cell carcinoma, recurrence or histologic signs of malignant transformation of a lesion may be considered to have a neoplasm of low grade malignancy and these patients must be followed closely. PMID- 8512368 TI - HIV testing of great value to the ESRD patient. PMID- 8512369 TI - An analysis of nursing's agenda for health care reform. AB - A review of Nursing's Agenda for Health Care Reform indicates that nursing has indeed turned its attention to the sociopolitical economic conditions that influence health. It appears that nursing has been redirected beyond the immediacy of individual concerns toward the larger social, political, and economic concerns. Though this agenda is very global and generic, it recognizes the complexities that make up the health care environment. PMID- 8512370 TI - Developing clinical practice guidelines: an interview with Ada Jacox. Interview by Barbara Bednar. AB - In 1992, the Agency for Health Care Policy and Research (AHCPR) released the first in a series of clinical practice guidelines designed to assist hospitals, practitioners, insurers, and consumers in learning more about which medical practices work and how that knowledge should be applied to delivering health care. In this interview, Ada Jacox, PhD, RN, co-chair of the pain management panel, discusses the development of clinical practice guidelines, their importance to health care professionals and consumers, and their possible impact on future practice. PMID- 8512371 TI - Idiopathic glomerulonephritis: is it IgA nephropathy? AB - Berger's disease or IgA nephropathy is a common form of glomerulonephritis that falls under the broad diagnostic category of primary glomerulonephritis. Diagnosis is made by clinical presentation and morphological changes noted on a biopsy of renal tissue. The exact cause is not known. The literature does implicate an immune-complex mediated syndrome and/or a defect in mucosal immunity as possible pathogenic mechanisms. With the advances made in diagnostic techniques, IgA nephropathy is now recognized as the most common type of glomerulonephritis in the world. PMID- 8512372 TI - Caretakers' informational needs after their children's renal or liver transplant. AB - The objectives of this research were to identify the information needs and concerns of the primary caretakers of pediatric renal and liver transplant recipients. A descriptive exploratory design was used. The major concerns expressed by the subjects were rejection, infection, normalization of the child and family unit, and reintegration into society. When nurses can anticipate these family's needs, anxiety may be decreased and the family and child may cope more effectively. PMID- 8512373 TI - Effect of an educational intervention on nurses' knowledge of a peritoneal dialysis cycler. AB - The effect of an innovative educational technique using pocket-sized problem solving cards on staff nurses' knowledge of the peritoneal dialysis cycler was examined. While there was no significant difference on knowledge scores between the experimental and control groups, a significant difference was found on pretest and posttest scores when the groups were combined. PMID- 8512374 TI - Research series: Part 2 of 6. Annotated bibliography: research proposal development and literature review. PMID- 8512375 TI - Clinical management of a hemodialysis patient with metastatic hypernephroma receiving experimental alfa interferon therapy. AB - The nursing interventions needed to promote optimal care for D.S. forcefully reminded the nurses of the challenges of nursing practice. The physiologic and emotional impact of the disease processes (ESRD and cancer), and the nature of chronic illness with concurrent experimental interferon therapy required continuous attention as the combined therapies progressed. The goals and interventions outlined are familiar to nephrology nurses. They are very effective in assisting this patient to adjust and to meet the expected outcomes. The unique nature of every patient remains the constant in our clinical practice. Nursing must continue to forge ahead in assessing a patient's needs, but always remembering that these needs must support the patient's relationship with his/her world. PMID- 8512376 TI - Case management of the anemic patient: epoetin alfa--focus on adequacy of dialysis. AB - For most patients, therapy with Epoetin alfa reverses anemia and provides them with many benefits, including an improved quality of life. Although some clinicians have expressed concern about the effect of an increased hematocrit on dialysis efficiency, peritoneal dialysis is unaffected, and changes in hemodialysis efficiency are usually not clinically significant. However, close monitoring of the adequacy of dialysis is always warranted. By tracking the results of serum chemistry tests, analyzing trends in urea kinetic modeling, providing patient education, and intervening early when a problem is detected, nurses can help ensure that patients receive the maximum benefit from their treatment regimen. PMID- 8512377 TI - Aseptic necrosis following transplant. PMID- 8512379 TI - Membership within ANNA offers benefits to renal transplant nurses. PMID- 8512378 TI - Benazepril: a new ACE inhibitor. AB - Benazepril (Lotensin) is an ACE inhibitor that can be safely used in renal and liver disease. Statistical analysis of both single and repeated 10 mg oral doses shows no significant difference in action between young patients and those over 55. All ACE inhibitor drugs are in a homogenous class. One advantage that benazepril has over the others is convenience. It can be taken any time of day, with or without food, and most often is only needed once a day. This is important to our patients who are on multiple medication regimens. There are no clinically important pharmacologic interactions with digoxin, warfarin, naproxen, cimetidine, hydrochorothiazide, furosemide, propranolol, atenolol, or chlorthalidone. PMID- 8512381 TI - Barrett's esophagus: another esophageal sphinx. PMID- 8512380 TI - Efficacy and safety of the superior-septal approach to the mitral valve. PMID- 8512382 TI - The Bjork-Shiley dilemma. PMID- 8512383 TI - The 1900 tuberculosis epidemic--starting point of modern thoracic surgery. PMID- 8512384 TI - Effects of insufflation on hemodynamics during thoracoscopy. AB - Thoracic procedures once requiring open thoracotomy are now being performed with video-assisted thoracoscopy. To visualize adequately the intrathoracic structures, creation of an artificial pneumothorax by carbon dioxide insufflation under positive pressures has been advocated. We hypothesized that positive pressure insufflation during thorascopy would cause significant hemodynamic compromise. Eight healthy female pigs underwent general endotracheal anesthesia and placement of monitoring lines. After placement of a thorascope, baseline hemodynamic measurements were obtained at 0 mm Hg (atmospheric pressure). Measurements were taken randomly at 5, 10, and 15 mm Hg using carbon dioxide insufflation after stabilization at each pressure. Data were analyzed using Page's test for noparametric variables. Insufflation pressures of 5 mm Hg or greater resulted in significant decreases in cardiac index, mean arterial pressure, stroke volume, and left ventricular stroke work index, whereas central venous pressure increased (p < 0.001). Changes in heart rate were not significant. We do not recommend routine positive-pressure insufflation during thorascopy because of the significant hemodynamic compromise in our experimental model. PMID- 8512385 TI - Cardiopulmonary bypass in patients with previously completed stroke. AB - It has been assumed that patients with neurological residua after a completed stroke are at increased risk of neurological complications associated with cardiac operations requiring cardiopulmonary bypass. To evaluate these assumptions, we reviewed retrospectively 1,163 consecutive patients undergoing cardiac operations with cardiopulmonary bypass. Among these 1,163 patients were 43 patients having a previously completed stroke with neurological residua, but without clinically significant extracranial carotid artery disease. Forty-one underwent coronary artery bypass grafting; of these, 1 required concomitant aortic valve replacement, 1 had mitral valve replacement, and 1 had aortic valve replacement. There was one death in this group of 43 patients, due to massive pulmonary embolism. Only 1 of these 43 patients experienced new neurological symptoms after operation, which would appear to indicate that patients with a previous, completed stroke may not be at increased risk of neurological complications from cardiac operations requiring cardiopulmonary bypass. PMID- 8512386 TI - Influence of pancreatic and biliary reflux on the development of esophageal carcinoma. AB - We previously presented an experimental model of Barrett's adenocarcinoma of the esophagus by demonstrating that esophagojejunostomy combined with subcutaneous injection of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats resulted in development of adenocarcinoma in the distal esophagus. The present study was devised to investigate the influence of pancreatic and biliary duodenal-content reflux on the induction of esophageal carcinoma. Three groups of 8-week-old Sprague-Dawley rats were controls: the first was exposed to pancreatic reflux, the second to biliary reflux, and the third to both. The other three experimental groups were similar except that a 1/100 LD50 dose of 2,6 dimethylnitrosomorpholine was injected subcutaneously weekly, starting on day 15. Carcinoma of the esophagus was induced only in animals receiving the carcinogen after exposure to either pancreatic reflux (3/22, 13%) or pancreatic and biliary reflux (9/27, 33%). Half of the carcinomas were adenocarcinoma and half were squamous cell carcinoma. These findings suggest that under these experimental conditions, in which the carcinogen is used in a low dose, esophageal carcinoma is induced only when pancreatic secretions are present in the duodenal-content reflux. Biliary reflux, however, appears to exert a cocarcinogenic effect when combined with pancreatic secretions. The clinical relevance of these findings needs further evaluation. Conceivably, the elimination of pancreatic and biliary duodenal-content reflux in patients with documented Barrett's mucosa may inhibit the progression from metaplasia to adenocarcinoma. PMID- 8512387 TI - VATS-Argon Beam Coagulator treatment of diffuse end-stage bilateral bullous disease of the lung. AB - Diffuse bullous disease of the lungs remains an unrelentless, debilitating, terminal disease. Intensive medical therapy can give transient relief of symptoms. Thoracotomy and resection has not always been successful and can be associated with an increased mortality and morbidity. Eight patients with end stage bullous disease, unresponsive to medical therapy and not considered to be candidates for a thoracotomy, underwent unilateral video-assisted thoracic surgical ablation of bullae using the Argon Beam Coagulator. Six men and 2 women ranging in age from 28 to 71 years reported a decrease in dyspnea. Three patients restudied had an increase in forced expiratory volume in 1 second of 34%. Postoperatively, 7 patients had an air leak, pneumonia developed in 2 patients, and 3 patients had massive subcutaneous emphysema after parietal pleurectomy. Hospitalization averaged 13.6 days. All patients made a complete recovery, and each was subjectively improved. Steroid use decreased, oxygen requirements decreased, dyspneic episodes decreased, infections decreased, and endurance increased. In 3 patients with a limited follow-up evaluated postoperatively, video-assisted thoracic surgery and the Argon Beam Coagulator seemed to be beneficial for treating advanced, generalized bullous disease. PMID- 8512388 TI - Strategy for the reduction of stroke incidence in cardiac surgical patients. AB - Atherosclerosis of the ascending aorta (AAA) and severe carotid artery disease are risk factors for stroke in cardiac surgical patients. Twelve hundred of a consecutive series of 1,334 patients 50 years of age or older having a cardiac operation were screened for the presence of AAA by intraoperative ultrasonographic scanning and for the presence of carotid artery occlusive disease (791 of 798 patients > or = 65 years of age and younger symptomatic patients) by carotid duplex scanning. Coronary artery disease was present in 88% of the patients. Patients with moderate or severe AAA (n = 231; 19.3% of the total) were treated by ascending aortic replacement (n = 27) or by modified, less extensive techniques (n = 168) to avoid the atherosclerotic areas. Thirty-three patients had combined carotid endarterectomy and cardiac operation. Thirty-day mortality and stroke rates for the 1,200 patients were 4.0% and 1.6%, respectively. The stroke rate was low (1.1%) among the 969 patients with no or mild AAA. It was zero among 27 patients with moderate or severe AAA who had ascending aortic replacement and among the 33 patients who had carotid endarterectomy. The stroke rates were higher for 111 patients with moderate or severe ascending aortic disease who had only minor interventions (6.3%) and for 16 patients with severe carotid artery disease who did not have carotid endarterectomy (18.7%). Screening for AAA and carotid artery disease and aggressive surgical treatment of moderate or severe AAA and severe or symptomatic carotid artery disease appears to reduce the frequency of stroke in older cardiac surgical patients. PMID- 8512389 TI - Fate of small homograft conduits after early repair of truncus arteriosus. AB - Neonatal repair of truncus arteriosus is being performed in a number of centers, often with the use of small homograft conduits. The fate of the homograft and the risk of replacement were the subjects of this study. Between January 1987 and October 1991, 43 infants aged less than 3 months (range, 3 to 90 days) underwent primary repair of truncus arteriosus including implantation of a valved homograft conduit (diameter, 7 to 12 mm). Twenty-nine had follow-up of more than 6 months (range, 6 to 65 months; mean, 21.9 months). After a mean period of 31 months (range, 8 to 65 months), 7 patients showed obstruction with right ventricular pressures at least 75% systemic and underwent either a conduit change (n = 5) or a patch augmentation (n = 2). Mean cardiopulmonary bypass time at reoperation was 99 minutes; mortality was zero. Five other children are known to have a right ventricular pressure of 50% to 60% systemic, 2 having undergone balloon dilation. Statistical comparison of the patients with conduit reoperation or high right ventricular pressure (n = 12) with the rest of the population (n = 17) revealed an elevated pulmonary artery to right ventricular pullback gradient on postoperative day 1 after the repair (7.7 versus 1.3 mm Hg; p = 0.001) and choice of an aortic over a pulmonary homograft (100% versus 64.7%; p = 0.065) as significant risk factors. Age and weight at repair, postoperative pulmonary artery pressure, length of follow-up, and size of the homograft showed no significant differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512390 TI - Mitral valve operation via an extended transseptal approach. AB - The extended transseptal approach to the mitral valve has been used for 71 consecutive procedures. Four patients died; none had complications directly attributable to the exposure. Twenty underwent a primary reparative procedure; 30, a primary replacement procedure; and 21, a repeat procedure. Despite division of the sinus node artery, 26 of 32 patients with sinus rhythm preoperatively had sinus rhythm postoperatively; 4 had atrial fibrillation postoperatively. Twenty seven of 37 patients with atrial fibrillation preoperatively had atrial fibrillation postoperatively; 8 had sinus rhythm postoperatively. Because the exposure provided by this extended transseptal approach is superior to that of standard approaches, we now use it routinely for mitral valve operations. PMID- 8512391 TI - A reliable bridge to cardiac transplantation: the TCI left ventricular assist device. AB - The Thermo Cardiosystems (TCI) HeartMate, a pneumatically driven, implantable left ventricular assist device, was designed for long-term support of the failing heart. Between February 1990 and August 1992, the HeartMate was implanted in 11 heart transplant candidates because of profound deterioration of left ventricular function. Patients had a mean cardiac index of 1.6 L.min-1 x m-2 and a mean pulmonary capillary wedge pressure of 33 mm Hg despite maximal pharmacologic support with at least three inotropic medications. In addition, 5 patients were being supported with an intraaortic balloon pump. Nine patients were bridged successfully to cardiac transplantation. The mean cardiac index after implantation of the left ventricular assist device was 3.2 L.min-1 x m-2. Support ranged from 2 to 143 days (mean duration, 60 days). One patient died early of low output secondary to right heart failure, and a second died of air embolism, which occurred intraoperatively. All surviving patients became fully ambulatory. There were no thromboembolic complications during a total of 658 patient-days of support on a regimen of only 80 mg of aspirin daily. The 9 bridged patients are currently alive 4 to 34 months after transplantation. The TCI HeartMate provides safe and effective hemodynamic support with low risk of complications and virtual freedom from thromboembolism on a regimen of minimal anticoagulation. PMID- 8512392 TI - Superior cerebral protection with profound hypothermia during circulatory arrest. AB - The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001). PMID- 8512393 TI - Extended resection of pulmonary metastases: is the risk justified? AB - Extended resection of pulmonary metastases by pneumonectomy or by pulmonary resection en bloc with chest wall or other thoracic structures (diaphragm, pericardium, superior vena cava) is infrequently performed as survival benefit is presumed low. Between 1981 and 1992, 38 patients underwent extended resection for pulmonary metastases (24 men, 14 women; average age, 48 years) from various primary neoplasms. Thirty-three patients (33/38, 87%) had complete resection. Five-year actuarial survival was 25.4%. Mortality was 5.3% (2/38) and occurred in patients undergoing pneumonectomy (2/19, 10.5%). Nineteen patients underwent pneumonectomy, and 19 patients had other assorted resections: pulmonary resection en bloc with chest wall in 11 and pulmonary resection en bloc with other thoracic structures in 8. Actuarial median survival (median, 27 months) did not differ between patients having pneumonectomy and those having pulmonary resection en bloc with chest wall or other thoracic structures. Initial disease-free interval (median) was no different between those patients undergoing pneumonectomy (32 months) or other type resection (35 months; p = 0.16). Median survival for extended resection as the initial operation for pulmonary metastases was 28 months compared with 14 months for all others (p = 0.095). Pneumonectomy for pulmonary metastases may be performed with operative risk equivalent to pneumonectomy for primary bronchogenic carcinoma. Patients may safely undergo extended resection of pulmonary metastases by pneumonectomy or in continuity with chest wall or other thoracic structures. Despite advanced localized metastatic disease, some patients achieve long-term survival after pneumonectomy and extended resection for pulmonary metastases. PMID- 8512394 TI - Thoracic approaches to anterior spinal operations: anterior thoracic approaches. AB - We performed a retrospective review of 36 patients aged 23 to 71 years (mean age, 52 years) who underwent 46 operations through a thoracic or thoracolumbar approach for orthopedic or neurosurgical procedures at Emory University Affiliated Hospitals. Pathologic indications for operation were metastatic disc disease in 10, herniated nucleus pulposus in 11, osteomyelitis in 6, vertebral fracture in 2, spinal deformities in 4, spinal abscess in 1, Pott's disease in 1, and liposarcoma in 1. Major indications for operation were infection and progressive paraparesis or paresthesias. Surgical approach consisted of a posterior lateral thoracotomy in 23, thoracotomy with retroperitoneal exposure in 6, thoracoabdominal exposure in 4, and cervical/upper sternotomy in 3. Diaphragmatic mobilization was required in 12. Surgical approach is dictated by the level of the lesion and its length. Lesions of T1 to T6 are approached through an upper sternotomy or right thoracotomy; lesions of T6 to L3, through a left thoracotomy with or without diaphragmatic mobilization. Specific techniques of segmental vessel division, diaphragmatic mobilization, and evaluation of artery of Adamkiewicz are emphasized. Rib grafts are harvested as needed. The thoracic surgeon can greatly enhance preoperative assessment, operative exposure and closure, and postoperative care for patients undergoing thoracotomy for spinal conditions. PMID- 8512395 TI - Effect of a free radical scavenger on cadaver lung transplantation. AB - The pulmonary donor pool would increase substantially if lungs could be safely transplanted after cessation of circulation. To determine whether the addition of the free radical scavenger dimethylthiourea to the perfusate of cadaver lungs could improve graft function, canine donors were sacrificed, and lungs retrieved 2 hours after death. In a blinded fashion, dimethylthiourea was added to the modified Euro-Collins solution and infused into recipients (n = 9) perioperatively; a placebo was included in the perfusate of control animals (n = 9). Donor animals were ventilated with 100% oxygen only during flush and harvest. Recipients were rendered dependent upon the single left transplanted lung by occlusion of the right pulmonary artery and bronchus 1 hour after transplantation. Ventilation was maintained at a constant inspiratory oxygen fraction of 0.4. Recipients were followed up for 8 hours or until death. Three of 9 control animals survived the 8-hour observation period, whereas 6 of 9 recipients of cadaver lungs harvested with dimethylthiourea survived the observation period. Two deaths in the dimethylthiourea group occurred after 7 hours, implying that the effects of the ischemia and reperfusion injury were ameliorated by the use of this agent in this model. This study supports the notion that perfusate modification may improve the yield of cadaver lung retrieval and may allow for transplantation of lungs harvested from cadavers after cessation of circulation. PMID- 8512396 TI - Retained intracardiac air in open heart operations examined by transesophageal echocardiography. AB - Using transesophageal echocardiography during open heart operations, we found another form of retained intracardiac air, "pooled air," in addition to the form of "bubbles" that had been reported by other authors. The pooled air was detected in all of 13 patients (100%); it was located at the right upper pulmonary vein in 13 (100%), left ventricular apex in 9 (69.2%), left atrium in 8 (61.5%), right coronary sinus of Valsalva in 8 (61.5%), left atrial appendage in 4 (30.8%), and left upper pulmonary vein in 3 (23.1%). The pooled air was found also in the pulmonary artery in 6 of 8 patients (75.0%) in whom the pulmonary artery was clearly visualized. In 1 patient, 5 mL of air was aspirated from the left ventricular apex, followed by a reduced size of the air on the transesophageal echocardiographic image. Because intracardiac air rapidly changes its locations and appearances, continuous monitoring is important, especially at weaning from bypass. The long-axis view of the heart is useful not only for detecting and locating the air, but also for guiding and evaluating the procedures to remove air. PMID- 8512397 TI - Thoracic versus lumbar epidural fentanyl for postthoracotomy pain. AB - Thirty patients were prospectively randomized to receive either thoracic or lumbar epidural fentanyl infusion for postthoracotomy pain. Epidural catheters were inserted, and placement was confirmed with local anesthetic testing before operation. General anesthesia consisted of nitrous oxide, oxygen, isoflurane, intravenous fentanyl citrate (5 micrograms/kg), and vecuronium bromide. Pain was measured by a visual analogue scale (0 = no pain to 10 = worst pain ever). Postoperatively, patients received epidural fentanyl in titrated doses every 15 minutes until the visual analogue scale score was less than 4 or until a maximum fentanyl dose of 150 micrograms by bolus and an infusion rate of 150 micrograms/h was reached. The visual analogue scale score of patients who received thoracic infusion decreased from 8.8 +/- 0.5 to 5.5 +/- 0.7 (p < or = 0.05) by 15 minutes and to 3.5 +/- 0.4 (p < or = 0.05) by 45 minutes. The corresponding values in the lumbar group were 8.8 +/- 0.6 to 7.8 +/- 0.7 at 15 minutes and 5.3 +/- 0.9 at 45 minutes (p < or = 0.05). The infusion rate needed to maintain a visual analogue scale score of less than 4 was lower in the thoracic group (1.55 +/- 0.13 micrograms.kg-1 x h-1) than in the lumbar group (2.06 +/- 0.19 microgram.kg-1 x h 1) during the first 4 hours after operation (p < or = 0.05). The epidural fentanyl infusion rates could be reduced at 4, 24, and 48 hours after operation without compromising pain relief. Four patients in the lumbar group required naloxone hydrochloride intravenously.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512398 TI - Cardiopulmonary function after pulmonary lobectomy in patients with lung cancer. AB - The effects of pulmonary lobectomy on cardiopulmonary function were investigated in 9 patients with lung cancer. Hemodynamic studies at rest and during exercise were performed before and 4 to 6 months after the operation. Differences in hemodynamics between before and after operation were observed with respect to heart rate, pulmonary arterial pressure, pulmonary vascular resistance index, and stroke volume index. Heart rate, pulmonary arterial pressure, and pulmonary vascular resistance index were significantly increased after operation, whereas stroke volume index was significantly decreased. It is thought that cardiac index was preserved by the increase in heart rate despite a decrease in stroke volume index associated with the decreased pulmonary vascular bed after the operation. When driving pressure and cardiac index were studied after operation, the pressure at rest and during exercise was higher, and the pressure-flow curve increased more steeply, as compared with the preoperative values. These results suggest a significant deterioration in cardiopulmonary function after lobectomy. As the patient characteristics were heterogeneous (five lobectomies and four bilobectomies), and their findings are limited, additional studies may be necessary in the future. PMID- 8512399 TI - Right internal mammary artery for myocardial revascularization: early results and indications. AB - The right internal mammary artery (RIMA) was used for coronary artery bypass grafting in 258 patients from October 1985 to October 1991. The RIMA was inserted as the only graft in 8 patients and in combination with the left internal mammary artery (LIMA) in 231 patients, the right gastroepiploic artery in 19, and autologous vein in 184. The patients received a total of 1 to 8 distal anastomoses (mean number, 3.3). A total of 64% of the RIMAs were anastomosed to the left anterior descending coronary artery. The primary indication for use of the RIMA was small-vessel disease in 86 patients, repeat bypass grafting in 32, varicose or stripped saphenous veins in 61, and "selected routine case" in 79. The early (< or = 30 days postoperatively) mortality rate in these four groups was 8.1%, 6.3%, 0%, and 0%, respectively (p < 0.01). Independent risk factors (logistic regression analysis) for early mortality were small-vessel disease, insufficient grafting, repeat coronary artery bypass grafting, diabetes, history of smoking, age of 60 years or older, and family history of ischemic heart disease. Combined into a risk index, these risk factors identified six risk groups with early mortality of 0% in the four low-risk groups and 5.6% and 58.3% in groups V and VI, respectively (p < 0.0001). No RIMA-related variables were risk factors for significant postoperative myocardial enzyme release. Intraoperative electromagnetic flow measurements revealed no differences between the RIMA and LIMA. Early angiographic patency in 50 patients was 98% for the RIMA and 93% for the LIMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512400 TI - Triple-valve operation in the young rheumatic patient. AB - Multiple-valve operation for the young rheumatic patient remains a problem. There is a paucity of information on the results of repair versus replacement in this age group. Between July 1988 and December 1991, 242 patients less than 20 years of age underwent a valve operation for rheumatic heart disease at our institution. Twenty-four (9.9%) of them had simultaneous mitral, aortic, and tricuspid valve procedures. The mean age was 14.71 years. All 24 patients were in functional class III or IV preoperatively. Valvar regurgitation was the predominant lesion. Four patients (16.7%) had active rheumatic myocarditis at the time of operation. Valve repair was attempted in the absence of infective endocarditis. Triple-valve repair was possible in 12 patients (50%). The hospital mortality rate was 16.7%. Reoperation was performed after repair in 9 patients (45%) without any deaths. The reason for reoperation was failure of the mitral valve repair in all patients, and the cause was technical in 3 patients, progression or recurrence of rheumatic myocarditis in 5, and endocarditis in 1 patient. The three late deaths (15%) were in patients who had mitral valve replacement. Valve repair was associated with a higher reoperation rate, and replacement of left-sided valves was associated with a higher early and late mortality. In conclusion, although valve repair would be ideal in the young rheumatic patient, multiple-valve repair is associated with a high reoperation rate. PMID- 8512401 TI - Open heart operation in patients suffering from hereditary spherocytosis. AB - Hereditary spherocytosis is a clinically heterogeneous, genetically determined red blood cell membrane disorder resulting in hemolytic anemia. Structural or functional disorders of the cytoskeletal proteins result in the formation of spherocytes, which lack the strength, durability, and flexibility to withstand the stresses of the circulation. This problem can be accentuated by the deleterious effects of the heart-lung machine. Three patients with hereditary spherocytosis underwent open heart operation with no deaths and no serious complications resulting from the hematologic defect. Splenectomy is recommended, although not essential, before a cardiac operation, and mechanical valves should perhaps be avoided. PMID- 8512402 TI - Bronchoplastic and angioplastic techniques in the treatment of bronchogenic carcinoma. AB - From 1979 to 1991, 51 bronchoplasties, 18 angioplasties, and 4 combined broncho angioplasties were performed for bronchogenic carcinoma. Sixteen patients underwent operation because of compromised pulmonary function; bronchoplasty, angioplasty, or the combined procedure was performed in the remaining 57 patients because of a suitable anatomic location of the neoplasm. Twenty-four patients had stage I disease, 32 stage II, and 17 stage IIIa. Three patients died postoperatively (3.65%). Major postoperative complications occurred in 20 patients (27.3%) (10 early, and 10 late). A completion pneumonectomy was required in 4 patients (5.4%), 2 for anastomotic stricture, 1 because of vascular thrombosis after angioplasty, and 1 for local recurrence after angioplasty. Three year and 5-year survival rates for the entire group were 55.4% and 40.8%, respectively. One-year and 3-year survival rates after angioplasty were 78.6% and 31.4%. Of the 4 patients who underwent a combined bronchoangioplastic procedure, 1 died after 23 months and 3 are alive and well after 11, 15, and 20 months. Survival was more favorable in the combined N0-N1 group (62% and 43.1%) than in the N2 group (23.4%), but the difference was not significant (p < 0.2). Three year survival after angioplasty was found to be lower than, although not significantly different from, the overall 3-year survival rate (31.4% versus 55.4%; p = not significant). No statistically significant differences were found among survival rates of patients with compromised and noncompromised pulmonary reserve. We conclude that bronchoplastic and angioplastic procedures are valid techniques as curative operations in carefully selected patients with bronchogenic carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512403 TI - Changes in right ventricular geometry and heart rate early after hemi-Fontan procedure. AB - To document and quantitate changes in right ventricular (RV) geometry and heart rate, we prospectively examined 35 consecutive patients with hypoplastic left heart syndrome under steady-state conditions (chloral hydrate sedation) before and after a bidirectional cavopulmonary anastomosis (hemi-Fontan) procedure. Right ventricular end-diastolic volume (RVEDV) was calculated as the product of RV cavity areas in two orthogonal planes divided by RV maximal length in either plane. After the hemi-Fontan procedure, RVEDV decreased by 33% from 33 +/- 13 to 22 +/- 11 mL (mean +/- standard deviation). Indexed RVEDV decreased from 86 +/- 37 to 57 +/- 28 mL/m2. The RV wall thickness at the diaphragm in subcostal frontal view (RVWD) increased by only 11% from 8 +/- 0.2 to 9 +/- 0.2 mm (p = not significant), but RVWD/RVEDV increased by 111% from 0.36 +/- 0.22 to 0.76 +/- 0.69 mm/mL (p = 0.002). The RV anterior wall thickness in subcostal sagittal view (RVWA) increased by only 13% from 7 +/- 0.2 to 8 +/- 0.2 mm (p = not significant), but RVWA/RVEDV increased by 103% from 0.31 +/- 0.20 to 0.63 +/- 0.54 mm/mL (p = 0.002). In 11 of 35 patients (31%), resting heart rate did not change (118 +/- 14 versus 108 +/- 9 beats/min; p = not significant); however, in 24 of 35 patients (69%), heart rate increased significantly (108 +/- 9 versus 127 +/- 10 beats/min; p = 0.05). In conclusion, RV wall thickness is high before the hemi-Fontan procedure and increases slightly in the first postoperative week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512404 TI - Preservation of the aortic valve in acute aortic dissection: long-term echocardiographic assessment and clinical outcome. AB - The aim of the present study was to determine the long-term status of the native aortic valve after surgical treatment of acute aortic dissection involving the ascending aorta. From 1972 to 1991, 93 patients underwent operation for type I or II aortic dissection. There were 76 men and 17 women. Mean age was 54 +/- 13 years. Eighty patients (86%) had a conservative procedure regarding the aortic root and aortic cusps: 74 had prosthetic replacement of the ascending aorta and 6, complete replacement of the aortic arch. Thirteen patients (14%) had simultaneous replacement of the aortic valve and the ascending aorta. The overall hospital mortality rate was 29% (27/93). The overall actuarial survival rate was 60.2% +/- 5.2%, 49.7% +/- 6.1%, and 35.9% +/- 8.1% at 5, 10, and 15 years, respectively. The survival rates for patients who had an ascending aortic procedure only were 63% +/- 5.5%, 54% +/- 6.5%, and 39% +/- 8.5% at 5, 10, and 15 years, respectively, and for patients who required aortic valve replacement, 45% +/- 14% and 22% +/- 17.5% at 5 and 10 years, respectively. Fifty long-term survivors (94% follow-up) with preservation of the aortic valve and aortic root were studied. Among them, 9 (18%) died within a mean interval of 97 +/- 46 months after operation. Causes of death were ischemic cardiac failure (2), aortic rupture or extension of dissection (4), renal disease (1), stroke (1), and sudden death (1). Forty-one patients had long-term clinical and echocardiographic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512405 TI - Vascular complications of intraaortic balloon pumping: unsheathed versus sheathed insertion. AB - Incidence of vascular complications in intraaortic balloon counterpulsation is still high despite major refinements in catheter design and techniques. One hundred twenty-six patients in whom intraaortic balloon pumping was attempted were divided into two groups on the basis of insertion technique. Group 1 included 77 patients in whom the conventional percutaneous insertion was used. In group 2 (n = 45 patients), a sheathless insertion technique was used. The overall vascular complication rate was 19.6%, with the lower limb ischemia as the most common complication. The vascular complication rate was 25.9% in group 1 and 8.8% in group 2 (p < 0.01). Lower limb ischemia was noted in 17 patients in group 1 and 3 patients in group 2 (p < 0.01). These results suggest that sheathless insertion of the intraaortic balloon pump catheter can minimize vascular complications. This technique will be especially useful in patients with peripheral vascular disease, in whom the likelihood of vascular complications is high. PMID- 8512406 TI - Comparison of response to injury in organ culture of human saphenous vein and internal mammary artery. AB - Autologous saphenous vein grafts, unlike internal mammary artery grafts, suffer many late occlusions as a result of excessive proliferation of vascular smooth muscle cells and the superimposition of atheroma on the resulting thickened intima. We investigated the possible basis of this difference using organ cultures. Internal mammary artery segments and freshly isolated and surgically prepared saphenous vein segments were obtained from patients undergoing coronary artery bypass grafting. Internal mammary artery and freshly isolated vein segments showed a high degree of endothelial coverage and medial cell viability that were maintained during culture. Surgically prepared veins showed partial endothelial denudation and medial cell injury, both of which tended to be reversed during culture. Neointimal thickening was greater in surgically prepared vein (72 +/- 13 microns; n = 11) than in freshly isolated vein (44 +/- 8 microns; n = 10) or internal mammary artery (34 +/- 4 microns; n = 13) segments. The occurrence of proliferating cells in the medial layer was also significantly greater in surgically prepared vein (2.8 +/- 1.0/mm; n = 11) than in freshly isolated vein (0.8 +/- 0.3/mm; n = 9) or internal mammary artery (0.6 +/- 0.3/mm; n = 10) segments. The data show that although the smooth muscle proliferation was similar in undamaged saphenous vein and internal mammary artery, it was significantly greater in damaged vein. This implies that the greater intimal proliferation seen in saphenous vein grafts may arise not from intrinsic differences in arterial and venous smooth muscle cells but from a greater susceptibility to injury. PMID- 8512407 TI - Lidocaine cardioplegia for prevention of reperfusion ventricular fibrillation. AB - Lidocaine addition to crystalloid cardioplegic solution for prevention of reperfusion ventricular fibrillation after the release of the aortic cross-clamp was studied in 50 patients undergoing coronary artery bypass grafting and in 30 patients undergoing mitral or aortic valve replacement. Twenty-six of the patients undergoing coronary artery bypass grafting received lidocaine, 100 mg/L of cardioplegia, whereas a control group of 24 patients received cardioplegia without lidocaine. In the group undergoing valve replacement, 14 patients received lidocaine cardioplegia and 16 patients served as control. In the coronary artery bypass grafting group, lidocaine cardioplegia reduced significantly the incidence of reperfusion ventricular fibrillation from 100% to 42%. In the valve group, lidocaine cardioplegia also reduced significantly the incidence of reperfusion ventricular fibrillation from 93% to 42%. In both groups, lidocaine cardioplegia decreased the number of direct-current countershocks required to defibrillate the heart, with no significant increase in the incidence of high-grade atrioventricular block. PMID- 8512408 TI - Factors confounding impedance catheter volume measurements in vitro. AB - The impedance catheter allows continuous measurement of ventricular volume. External influences have been described as causing parallel shifts in impedance measured volumes; however, factors affecting impedance measurements in a nonparallel manner have not been fully characterized. Accordingly, an impedance catheter was placed inside a latex balloon into which known volumes of normal saline solution were injected. Conductive and nonconductive materials were individually placed within the balloon. Impedance was measured with materials touching (T) or not touching (NT) the catheter. Impedance-measured volumes were plotted versus actual volumes. Compared with the line of identity (LID), a statistical difference (p < 0.05) was found in the slopes in the presence of metallic objects only. These included a pacing lead (T, NT) (mT = 1.32m mNT = 1.29 versus mLID = 1.00), titanium (T) (mT = 1.68 versus mLID = 1.00), and aluminum (NT) (mNT = 0.72 versus mLID = 1.00). These changes in slope indicate nonparallel effects on impedance that confound the ability of the impedance catheter to determine volumes in vitro. These observations imply that serial calibration of both the slope constant (alpha) and the intercept (parallel conductance) of impedance may be necessary for in vivo measurements of ventricular volume based on impedance in the presence of metallic objects. PMID- 8512409 TI - Heparin coating reduces blood cell adhesion to arterial filters during coronary bypass: a clinical study. AB - Deleterious effects of cardiopulmonary bypass (CPB) are partly sequelae of blood foreign surface reactions. Coating the inner surfaces of CPB sets with heparin has been shown to decrease activation of humoral cascade systems. The aim of this study was to investigate whether the heparin-coated CPB sets influence adhesion of blood cells to surfaces of arterial filters during CPB. Thirty-one patients undergoing coronary artery bypass grafting were studied. In the control group (C) standard CPB sets and standard doses of heparin (300 IU/kg) were employed; in the HC (heparin-coated) group, heparin-coated CPB sets and reduced heparin doses (range, 150 to 225 IU/kg) were used. Two additional groups were also studied; group FC (coated filter), with standard CPB sets and heparin-coated arterial filters (heparin dose, 300 IU/kg), and group OC (uncoated filter), with heparin coated CPB sets and standard arterial filters (heparin dose, 300 IU/kg). The inner surfaces of the arterial filters were examined after CPB with scanning electron microscopy. Scanning electron microscopy demonstrated almost clean surfaces in heparin-coated filters even when other parts of the circuit were uncoated. Using an arbitrary adhesion score, significant differences between the groups were noted in the adhesion grade; it was lowest in group HC (2.2 +/- 0.27 [mean +/- standard error of the mean]) versus group C (5.4 +/- 0.53; p < 0.001). In group FC it was marginally higher than in group HC but almost significantly lower than in group OC (2.6 +/- 0.68 versus 5.4 +/- 0.81; p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512410 TI - Efflux of adenosine and its catabolites during cold blood cardioplegia. AB - Levels of myocardial high-energy phosphates decrease during cardioplegia for open heart operations, with a subsequent increase in the level of adenosine and its metabolites. It has been demonstrated in experimental models that the effluent concentrations of purines can be used as a measure of the average myocardial energy state. Net adenylate loss and myocardial energy state were evaluated here by determining aorta-coronary sinus differences in levels of adenosine catabolites in 17 patients during cold blood cardioplegia for elective coronary artery bypass grafting. Repeated blood samples were taken before cross-clamping of the aorta, when cardioplegic solute was infused into the aortic root and grafts after five distal anastomoses, and after declamping of the aorta. The aorta-coronary sinus differences in levels of total purines increased 4.7-, 7.5-, 7.1-, 7.8-, and 10.2-fold (from the preclamp level of 1.7 +/- 0.7 mumol/L; p < 0.001) for grafts one through five anastomosed at an average of 19, 34, 50, 63, and 76 minutes after the aortic cross-clamp, respectively. Hypoxanthine and xanthine were present in the highest concentrations. Vasodilatory adenosine concentrations of 1 to 2 mumol/L were observed in the coronary sinus while the aorta was cross-clamped. There was a linear positive correlation between the aorta-coronary sinus purine differences and corresponding cross-clamp time (r = 0.62; p < 0.001). The metabolite differences settled at a more negative level after declamping of the aorta than that prevailing before placement of the cross clamp, suggesting continuous washout of adenosine and its catabolites during the 30-minute postclamp observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512411 TI - Pneumonectomy for unremitting hemoptysis in unilateral absence of pulmonary artery. AB - Unilateral absence of pulmonary artery is a rare malformation that can present as an isolated lesion or may be associated with other congenital heart defects. Clinical presentation is subtle when the lesion occurs alone, and may include hemoptysis, which results from rupture of abundant bronchial submucosal vessels perfused by enlarged systemic collaterals that supply the affected lung. Pneumonectomy is recommended as definitive treatment in such an adult patient. PMID- 8512412 TI - Perioperative paraplegia and multiorgan failure from heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia and thrombosis syndrome is a rare but devastating complication. We report a patient with heparin-induced thrombocytopenia in whom heparin-induced thrombocytopenia and thrombosis syndrome developed after a cardiac operation, complicated by acute thrombosis of the aorta followed by renal failure, paralysis, and ischemic necrosis of the lower extremities. The literature suggests aspirin, dipyridamole, and iloprost as effective prophylactic agents for perioperative heparin-induced thrombocytopenia and thrombosis syndrome. This unfortunate complication underscores the importance of close platelet count monitoring in all preoperative patients undergoing prolonged heparin therapy. PMID- 8512413 TI - Septal myectomy with a carbon dioxide laser for hypertrophic cardiomyopathy. AB - Septal myectomy with a noncontact carbon dioxide laser for hypertrophic cardiomyopathy is described. This technique results in improved visualization of the septum as the laser beam is held outside the heart and the resecting laser beam can always be clearly seen. We believe this approach provides an improved method of septal myectomy in hypertrophic cardiomyopathy. PMID- 8512414 TI - Tracheoesophageal fistula caused by mycobacterial tuberculosis adenopathy. AB - Tracheoesophageal fistulas resulting from a Mycobacterium tuberculosis infection are uncommon. We describe a patient with such a lesion that had the radiologic and clinic appearance of a malignant tracheoesophageal fistula. Use of an anterior cervical approach with one-stage esophageal repair along with tracheal resection and anastomosis allowed definitive diagnosis and treatment of this life threatening complication. PMID- 8512415 TI - Isolated congenital atresia of the left main coronary artery and atherosclerosis. AB - Successful surgical revascularization in an adult with isolated congenital atresia of the left main coronary artery with coexistent two-vessel atherosclerosis is described. This extremely rare anomaly must be differentiated from single right coronary artery and acquired occlusion of the left main coronary artery. Symptomatic myocardial ischemia in patients surviving to adulthood is an indication for surgical revascularization in them. PMID- 8512416 TI - Continuous retrograde cerebral perfusion during an aortic arch operation. AB - An 81-year-old woman presented with acute aortic regurgitation in the setting of an aneurysm of the ascending aorta and arch. The aortic valve, ascending aorta, and arch were replaced with a composite graft during continuous hypothermic total body perfusion. Continuous cerebral perfusion was carried out by low-pressure retrograde perfusion via the superior vena cava while perfusion of the lower body was maintained via a femoral arterial cannula. PMID- 8512417 TI - Closed technique for repair of right superior vena cava draining to left atrium. AB - A rare case of total anomalous drainage of a right superior vena cava to the left atrium is presented. The patient had an intact atrial septum and presented with cyanosis and a history of an earlier brain abscess. Complete repair was performed using a venoatrial shunt and without the use of cardiopulmonary bypass. PMID- 8512418 TI - Staged antrectomy and thoracoscopic truncal vagotomy for perforated peptic ulcer disease. AB - We report the case of a 40-year-old man with a perforated duodenal ulcer who underwent antrectomy at laparotomy, and in whom standard truncal vagotomy was not technically possible due to an intraabdominal abscess. Thoracoscopic truncal vagotomy performed at the level of the inferior pulmonary vein was successful in completely eliminating symptoms due to peptic ulcer disease without producing clinically significant morbidity. The minimal morbidity and short hospital stay suggest that thoracoscopic truncal vagotomy provides a reasonable alternative in patients with complicated intraabdominal abscesses due to peptic ulcer disease. PMID- 8512419 TI - Retrograde gastric varices in a patient with total cavopulmonary shunt. AB - Gastric varices formed in a patient who had undergone a total cavopulmonary shunt operation 7 years previously. The varices were found to be due to development of collaterals from high-pressure systemic vein to low-pressure portal vein. Bleeding gastric varix can be a late complication of total cavopulmonary shunt. PMID- 8512420 TI - Papillary fibroelastoma of mitral valve chorda. PMID- 8512421 TI - New modified Bentall procedure: Carrel patch and inclusion technique. AB - In Bentall-type procedures, the bleeding and dehiscence occurring around the coronary ostial anastomosis still remain major complications. To reinforce the coronary anastomosis and shorten the time required for hemostasis, a Carrel patch and inclusion technique was employed without any subsequent complications in 13 patients. We excised the coronary ostium with a collar of the aortic wall while leaving epicardium on the aortic wall, anastomosed it to the composite graft, and then included the graft with the aortic wall. PMID- 8512422 TI - Pericardial closure without pericardial substitute. AB - Primary closure of the native pericardium is recommended whenever possible, and pericardial substitutes are advocated when primary closure is not feasible. To avoid foreign material, we have employed a unique method of dissection to allow mediastinal coverage without tension. PMID- 8512423 TI - Fabric heart retractor for coronary artery bypass operations. AB - A new device for heart retraction during coronary artery bypass operations has been developed. It provides safe and steady support and an unobstructed view of the lateral, posterior, and inferior surfaces of the heart; in addition, it is easy to handle. PMID- 8512424 TI - Balloon method for detecting inadequate double-lumen tube cuff seal. AB - A method for detecting air leak when using a double-lumen endobronchial tube is described. The ventilatory circuit is directly attached to the lumen of the ventilated lung. A balloon is fitted snugly over the open lumen of the tube to the nonventilated lung. If lung separation is incomplete, the balloon will inflate with each ventilation. PMID- 8512425 TI - Computed tomographic scan in N2 disease. PMID- 8512426 TI - Electrocardiographic detection of rejection. PMID- 8512427 TI - Newly devised instrument for spraying aerosolized fibrin glue in thoracoscopic operations. PMID- 8512428 TI - Revival of the radial artery for coronary artery bypass grafting: l'histoire se repete. PMID- 8512429 TI - Retained intraaortic balloon. PMID- 8512430 TI - Retrograde blood cardioplegia. PMID- 8512431 TI - A simple and useful maneuver to open the sternum in redo operations. PMID- 8512432 TI - Complication of automatic implantable cardioverter defibrillator implantation. PMID- 8512433 TI - When can treatment be withheld in patients with suspected pulmonary embolism? PMID- 8512434 TI - A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women. AB - The purpose of this article was to review, with special attention to the hypothesized mechanisms of atherosclerosis and thrombosis, the literature on the association of estrogens and progestins with cardiovascular disease. The data sources included recent reviews and their citations as well as literature searches of Medline. For coronary heart disease, we relied on a recent meta analysis; for the lipid effects of estrogens and progestins, we refer to recent reviews and studies; for stroke, we identified all cohort and case-control studies; and for the effects of hormones on coagulation factors, we identified all relevant studies. The lipid effects of estrogens in postmenopausal women probably prevent atherosclerosis, and we would expect long duration of use rather than current use to provide the greatest benefit. Few epidemiologic studies have, however, assessed duration of estrogen use. High doses of estrogens are likely to be thrombogenic during current use, and it is possible that even moderate doses may increase the risk of clotting among women who smoke or who have existing coronary atherosclerosis. Compared with the lipid effects of estrogens alone, the lipid effects of combined therapy with progestins may increase atherosclerosis. The effect of progestins on coagulation factors is largely unknown, and no epidemiologic study has assessed the risk of cardiovascular disease associated with the use of combined hormone therapy in postmenopausal women. Cardiovascular risk or benefit associated with the use of postmenopausal hormones may involve several competing mechanisms, including effects on prostaglandins and vascular tone as well as atherosclerosis and thrombosis. PMID- 8512435 TI - Evaluation of a portable prothrombin time monitor for home use by patients who require long-term oral anticoagulant therapy. AB - BACKGROUND: The anticoagulant activity of warfarin sodium is monitored by the prothrombin time (PT). The introduction of a portable PT monitor has raised the possibility that patients could reduce the inconvenience of anticoagulant therapy by measuring their PT at home. We performed this study to determine the feasibility and accuracy of home use of the portable PT monitor. METHODS: A prospective cohort study was performed in consecutive eligible patients who required long-term anticoagulant therapy. Patients performed multiple measurements of their PT at home by means of the portable monitor and at their usual laboratory within a 4-hour interval. The accuracy of the portable monitor was evaluated by two criteria for agreement. Standard agreement was achieved if the portable monitor and laboratory results were both either within or outside the patient's targeted therapeutic range or if the two results were within 0.4 international normalized ratio units of each other. Expanded agreement was achieved if both the portable monitor and laboratory results were within +/- 0.4 international normalized ratio units of the targeted therapeutic range. RESULTS: Forty patients (19 men and 21 women, aged 25 to 74 years) were followed up for 6 to 24 months by means of the portable PT monitor. The mean level of agreement achieved per patient was 83% (95% confidence interval, 79% to 87%) by the standard criteria and 96% (95% confidence interval, 94% to 98%) by the expanded criteria. Twenty-seven patients (68%) and 39 patients (98%) achieved more than 80% agreement by the standard and the expanded criteria, respectively. Questionnaire results revealed that 97% of the patients preferred using the portable monitor to measure their PT. CONCLUSIONS: Patients receiving long-term anticoagulant therapy achieved a high rate of clinically important agreement between self-measurements of the PT with the use of a portable monitor and laboratory PT results. Patients strongly preferred using the portable monitor to measure their PT levels. The use of the portable monitor as the primary method for measuring the PT can be recommended in selected patients receiving long-term anticoagulant treatment. PMID- 8512436 TI - The risk of occupational human immunodeficiency virus infection in health care workers. Italian Multicenter Study. The Italian Study Group on Occupational Risk of HIV infection. AB - BACKGROUND: More than 50 cases of occupationally acquired human immunodeficiency virus (HIV) infection in health care workers (HCWs) have been reported worldwide. Determinants of injuries and of infection are important to investigate to design effective prevention programs. METHODS: In Italy, 29 acute-care public hospitals were enrolled in a multicenter study between 1986 and 1990. At each facility, all HCWs were enrolled who reported percutaneous, mucous-membrane, or nonintact-skin exposure to the body fluids and tissues to which universal precautions apply from an HIV-infected patient. Data were collected at the time of the incident on clinical status of the HIV-infected source, circumstance and type of exposure, and use of infection control precautions. The HCWs were followed up clinically and serologically for HIV infection at 1, 3, 6, and 12 months. RESULTS: A total of 1592 HIV exposures were reported in 1534 HCWs; most exposures (67%) occurred in nurses, followed by physicians and surgeons (17.5%). Needlesticks were the most common source of exposure (58.4%), followed by nonintact-skin and mucous membrane contamination (22.7% and 11.2%, respectively) and cuts (7.7%). At the time of exposure, 77.5% of the HCWs knew or suspected that the source patient was HIV infected. Two seroconversions were observed among a total of 1488 HCWs followed up for at least 6 months: one occurred in a student nurse who had been stuck with a needle used for an HIV antibody-negative, p24 HIV antigen-positive drug addict; the other was in a nurse who experienced mucous-membrane contamination with a large quantity of blood from an HIV-positive hemophilic patient. The seroconversion rate was 0.10% after percutaneous exposure (1/1003; 95% confidence interval, 0.006% to 0.55%) and 0.63% after mucous-membrane contamination (1/158; 95% confidence interval, 0.018% to 3.47%). CONCLUSIONS: The study demonstrates a small but real risk of HIV infection after percutaneous and mucous-membrane exposure to blood of HIV-infected patients and that transmission can occur during the "window period" of infection. Furthermore, exposures to HIV are not infrequent, and many exposures could be prevented with the use of barrier precautions, appropriate behaviors, and safer devices and techniques. PMID- 8512437 TI - The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. AB - BACKGROUND: Metoclopramide hydrochloride, a neuroleptic dopamine receptor antagonist used to treat gastric ailments, is reported to cause extrapyramidal movement disorders. The goals of this study were (1) to determine the prevalence and severity of tardive dyskinesia and acute extrapyramidal movement syndromes including akathisia, acute dystonia, and drug-induced parkinsonism in metoclopramide-treated patients and (2) to compare the prevalence and severity of tardive dyskinesia in metoclopramide-treated diabetics and nondiabetics. METHODS: From a list of metoclopramide-treated patients received from the Portland (Ore) Veterans Affairs Medical Center pharmacy, 53 patients met inclusion criteria and 51 (96%) agreed to participate. Controls consisted of a convenience sample drawn from the Portland Veterans Affairs Medical Center Outpatient Clinic who were matched to subjects on age (+/- 10 years), gender, and presence or absence of diabetes. Of 61 potential controls contacted, 51 (84%) agreed to participate. Metoclopramide-treated subjects and controls were seen by a rater who was "blind" to all diagnoses and treatments. The rater performed a standardized examination used to elicit signs and symptoms of tardive dyskinesia and acute extrapyramidal movement syndromes. RESULTS: The relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93 to 2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5 to 10.5). Metoclopramide treated patients had significantly greater severity of tardive dyskinesia, drug induced parkinsonism, and subjective akathisia than controls. Use of metoclopramide was associated with impairment in ambulation and increased use of benzodiazepines. Metoclopramide-treated diabetics had significantly greater severity of tardive dyskinesia than metoclopramide-treated nondiabetics. CONCLUSIONS: Metoclopramide use is associated with a significantly increased prevalence and severity of several extrapyramidal movement disorders. PMID- 8512438 TI - Psychiatric and otologic diagnoses in patients complaining of dizziness. AB - BACKGROUND: Dizziness is a common and disabling symptom in primary care practice, especially among the elderly. Though there are many organic causes of dizziness, the results of medical workups are negative in the majority of patients. METHODS: A total of 75 patients with dizziness who were referred to a community otolaryngology practice received a structured psychiatric diagnostic interview (National Institute of Mental Health Diagnostic Interview Schedule) and questionnaires that assessed psychological distress as well as a complete otologic evaluation, including electronystagmogram. Patients with evidence of a peripheral vestibular disorder were compared with those without such evidence. RESULTS: While psychiatric diagnoses were present in both those with and without evidence of a peripheral vestibular disorder, those without such evidence had a greater mean number of lifetime psychiatric diagnoses as defined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, and specifically, a greater lifetime prevalence of major depression and panic disorder. This group also more frequently met criteria for somatization disorder, had more current and lifetime unexplained medical symptoms, and had more severe current depressive, anxiety, and somatic symptoms. CONCLUSIONS: Psychiatric diagnoses are common among patients with dizziness referred for otologic evaluation who do not show evidence of a peripheral vestibular disorder. Specific psychiatric disorders should be part of the differential diagnosis of patients who present with dizziness. PMID- 8512439 TI - Lower levels of cigarette consumption found in smoke-free workplaces in California. AB - OBJECTIVE: We examined the relationship between workplace smoking policies and smoking prevalence and cigarette consumption. METHODS: California residents were questioned by telephone with the 1990 California Tobacco Survey. All respondents (11,704) above age 18 years who were employed indoors were used. Respondents were asked about smoking status, workplace smoking policy, desire to quit, and smoking history. Logistic regression was used to determine the relationship of workplace smoking policy to smoking status, accounting for demographic variables. RESULTS: Prevalence of regular smokers was significantly lower in smoke-free workplaces than in those with no restrictions (13.7% vs 20.6%, P < .001). Continuing regular smokers in smoke-free workplaces smoked fewer cigarettes than those in workplaces with no restrictions (296 vs 341 packs per year, P < .001). More comprehensive smoking policies were associated with smokers more likely to contemplate quitting (P = .014). CONCLUSIONS: Employees in smoke-free workplaces have a lower smoking prevalence and, among continuing smokers, lower cigarette consumption than individuals working where smoking is permitted. We estimate cigarette consumption among employees indoors is 21% below that if there were no smoking restrictions in California workplaces. Furthermore, if all California workplaces were smoke free, cigarette consumption among employees would be 41% below that if there were no workplace smoking restrictions, approximately a $406 million annual loss in sales to the tobacco industry. This study supports the hypothesis that smoke-free workplace policies are an effective public health measure for decreasing smoking prevalence and cigarette consumption among continuing smokers. PMID- 8512440 TI - Unrecognized coccidioidomycosis complicating Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus and treated with corticosteroids. A report of two cases. AB - Coccidioidomycosis is becoming increasingly recognized as an opportunistic infection among patients infected with the human immunodeficiency virus. We treated two cases of concomitant coccidioidomycosis and Pneumocystis carinii pneumonia. In each case, the diagnosis of coccidioidomycosis was delayed despite appropriate examination of bronchoalveolar lavage fluid. Both patients were treated with antimicrobial therapy directed against P carinii and given adjuvant corticosteroid therapy. In both cases, this led to clinical worsening and was associated with the development of a reticulonodular pulmonary infiltrate on chest roentgenograms. When coccidioidomycosis and Pneumocystis pneumonia occur concomitantly in patients with human immunodeficiency virus infection, the diagnosis of coccidioidomycosis may be delayed or missed. In such cases, corticosteroids may lead to overwhelming coccidioidomycosis. Development of a reticulonodular pulmonary pattern on chest roentgenograms is suggestive of this complication. PMID- 8512441 TI - Elevated blood lead levels associated with illegally distilled alcohol. AB - Whiskey produced in illegal stills (ie, "moonshine") remains an important and underappreciated source of lead toxicity in some rural counties of the Southeast. From March 5 through October 26, 1991, eight adult patients with elevated blood lead levels were identified at a rural county hospital in Alabama and were reported to the Alabama Department of Public Health notifiable disease surveillance system. A case-patient was defined as any person 17 years of age or more who presented to the hospital from January 1, 1990, through December 31, 1991, and had a blood lead level of 0.72 mumol/L or more (15 micrograms/dL or more). To identify cases and potential sources of lead exposure, we reviewed medical and laboratory records from the hospital, interviewed patients with elevated blood lead levels, and determined the lead content of moonshine samples. Nine patients met the case definition, including one patient who was not reported to the state. Patients ranged in age from 28 to 62 years; blood lead values ranged from 0.77 to 12.50 mumol/L (16 to 259 micrograms/dL). The most frequent signs of possible lead toxicity included seizures (six), microcytic anemia (five), and encephalopathy (two); one patient died. The only identified source of lead exposure for the nine patients was moonshine ingestion. Moonshine samples available from local stills contained sufficient amounts of lead (340 to 4600 mumol/L) to result in the observed blood lead levels. This investigation emphasizes the adverse health effects and ongoing public health impact of moonshine ingestion. PMID- 8512442 TI - Mitral valve prolapse and infective endocarditis. PMID- 8512443 TI - [Technique--a suitable means for prevention of sex offenses?]. AB - Women as potential victims of sexual offences are becoming less willing to accept these rules to word of, which frequently mean a loss of independence to a certain extent. More and more women are asking for alternative and appropriate defence measures for dangerous situations. The present article describes and discusses chances and limits of the utilization of new technical devices such as "miniature alarm transmitter". PMID- 8512444 TI - [Excessive gambling in prisoners. A statistical study of 72 criminals of various crime categories]. AB - After a brief introduction into the psychiatric problems of pathological gambling, the author presents a statistical study on 72 delinquents, amongst them 14 excessive gamblers. The special design of this investigation consists in two comparative studies between the gambling and the non-gambling subgroups, first within the total of delinquents secondly within the group of the drugs- and property-offenders. There is a great number of traits compared concerning e.g. family history, personal biography, social status, drug-consumption-behavior and clinical traits. It is clearly shown that excessive gamblers are markedly overrepresented in the last-mentioned group and that gamblers are to be distinguished by a number of characteristics from their group-mates even in this comparatively homogenous subgroup. Thus, they seem to be negatively loaded by the high prevalence of psychiatric abnormalities in their families, by a higher frequency of birth complications, infantile behavioral disorders and an even more marked seeking behavior for addictive drugs. PMID- 8512445 TI - [Prolonged survival after severe craniocerebral injury caused by an ax strike]. AB - The authors describe autopsy findings and neuropathological findings in the case of a man killed by an axe cut. Regardless of his expanded brain injuries he had survived for about 16 hours. PMID- 8512446 TI - [The effect of the phosphorus supply on the energy metabolism of growing swine]. AB - In growing barrows (live weight 17-30 kg) 3 g P/kg DM feed resulted in comparison to 6 g P/kg DM in 8% lower live weight gain. The lower live weight gain had no relation to N- and energy retention. The lower P feeding has only low effect on energy excretion in faeces and urine (1% of gross energy). A submarginal P feeding has no influence on N- and energy metabolism of growing pigs. PMID- 8512447 TI - [Estimation of the zinc requirement for broilers using their ability for selective zinc absorption and by dose-response relations]. AB - Broiler chicks are able to select an adequate dietary Zn-concentration in choice feeding. The zinc requirement should be ascertained by this method of self selection. 72 day-old chicks were divided into 9 groups and were kept over 5 weeks in individual cages. By gradually supplementing ZnSO4.7H2O to a semisynthetic basal diet with isolated soybean protein 5 diets were made with Zn concentrations of 14, 22, 30, 38 and 50 ppm, which respectively were fed to one group. The four other groups had to choose between two rations: 14/38; 14/50; 22/38; 22/50. Selective zinc intake was represented by a significant increase of dietary zinc concentration compared to random selection (mean of both diets). Feed intake, zinc intake and weight gain were measured daily and the end total feed consumption, live weight, feed conversion rate, plasma-zinc concentration and plasma-zinc binding capacity at the end of the experiment. In comparison optimal dietary zinc levels were estimated by dose-response relations, both by sigmoid growth curves and by broken-line model. With 30 ppm Zn chickens reached a high fattening level with daily weight gains of 60 g. Feed intake and growth rate were markedly reduced at a dosage of 14 and 22 ppm Zn, feed conversion rate was tendentially decreased below a level of about 34 ppm, whereas above zinc binding capacity reached a plateau. Birds self-selected a dietary zinc level of 32 ppm, which were adequate for the criteria feed intake and weight gains. Zinc requirements of about 40 ppm were assessed by conventional methods. PMID- 8512448 TI - [The determination of a gross utilization of 15N-lysine in laboratory rats. 2. Comparative testing with an antibiotic supplement to the diet]. AB - Wistar rats of a live weight of about 100 g received in 26 groups (4 animals/group) diets, each with a different lysine content. The rations given supplied the animals with 75%, 100% or 125% lysine of the calculated requirement. The source of protein in the diets was: barley (B), wheat (W), wheat gluten (WG), isolated soybean protein (assay protein) (S) or soybean meal (SM). For WG and S only the lysine levels 100% and 125% (SM = 116% and 125%) could be achieved. All diet groups were fed for 10 days with and without antibiotics (7 g Nebacitin/kg feed-DM). During the 7-day-period of the main experiment all 24 rations were supplemented with 0.5 g 15N-lysine/kg DM (48.3 atom-% 15N-excess, alpha aminogroup 95% 15N-labelled). The nitrogen balance was improved only after feeding antibiotics with the diet S 100. It may be supposed that Nebacitin saved the second limiting amino acid methionine against microbial degradation in the digestion tract. The biological value (BV) of feed-proteins declined in the case of the diets B and W in the presence of antibiotics because the absorbed nitrogen was higher, this calculation basis for BV was therefore also higher without an improvement of the N-utilization. The 15N-excretion in faeces was significantly lower after feeding the diets B, W and WG with antibiotics. The 15N-excretion in urine was elevated in the most cases of the antibiotic supplement. The determination of a gross utilization of lysine and 15N-lysine resp. in relation to the lysine retention (availability) was not possible, neither using a labelling of diets with 15N-lysine. PMID- 8512449 TI - Heat-induced formation of soluble Maillard reaction products and its influence on utilization of glucose by rumen bacteria. AB - In a series of experiments with pure strains of rumen bacteria the effect of heat induced formation of soluble Maillard reaction products on the utilization of glucose was examined. Maillard reaction products were prepared from glucose and amino acids, which were dissolved in a growth medium and autoclaved at 100 degrees C and 120 degrees C. Glucose was utilized almost completely in all cultures, no matter whether it was bound in Maillard products or not. The complexing of glucose with amino acids lowered the growth rate and growth yields in most rumen bacteria studied. In some strains, however, the effect of the Maillard reaction was small. It was concluded that the heat damage of carbohydrates in feedstuffs could be attributed to final stages of the Maillard reaction (formation of insoluble polymers), rather than to initial ones. PMID- 8512450 TI - Use of a combined synthetic fibre bag method to estimate the true total tract digestion of organic matter and nitrogen of hay and grass silage in cows. AB - A 4 x 4 Latin square experiment was designed to determine and compare the total tract digestion of organic matter (OM) and nitrogen of hay and grass silage by combining the ruminal and intestinal digestion estimates obtained by the rumen bag and mobile bag methods. The diets were composed of forage alone or 30% forage and 70% barley. The rumen degradation (RD) was calculated using the degradation constants a, b, and c obtained to the forages, according to the equation RD = a+bc/(c+k). Intestinal digestion of escape feeds was estimated using the feed residues that resisted rumen degradation during 16 hours. For comparative purposes, the total tract digestion was also calculated based on the actual rumen degradation of forages during 16 hours rumen incubation. The effect of dietary interaction on the digestion of forages was assessed. Rumen degradation values obtained by 16 hours incubation did not provide sufficient basis to estimate reliably the total tract digestion by the combined bag method. Using calculated RD total tract digestion of OM of hay and grass silage were rather close to conventional in vivo digestion coefficient of respective feeds similar in chemical composition, when barley was not included in the diet. With hay, but not with grass silage, barley always markedly reduced the rumen degradation and total digestion of OM. Barley supplementation always increased the proportion of feed digested in the intestine. Nitrogen digestion was always higher with grass silage than with hay, and the combined bag method produced N digestion values 17.6-22.0% units higher than those in the feed table. Barley supplementation did not affect the N digestion of the forages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512451 TI - [The effect of starch sources barley, corn and potatoes and their ration proportions on nutrient digestibility and energy utilization in ruminants. 2. Fractions of ruminally and postruminally digested nutrients in cattle]. AB - The investigations of this paper are part of a complex research project to develop energetic feed evaluation within the Net Energy Fat System. The aim was to obtain new results to estimate the relation between place as well as kind of nutrient digestion and energetic utilization of rations in cattle. The ruminal nutrient digestibility was measured in adult oxen on feeding level 1.7 by means of duodenal reentrant cannula for 9 rations including the starch sources barley, maize and potatoes and with their energy parts of 50, 25 and 10%. The intake of starch ranged from 484 to 2573 g/animal.d and the amounts of ruminal and postruminal digested starch from 444 to 2336 as well as 10 to 284 g/animal.d. For the organic matter, starch, water soluble carbohydrates and N free residual substances high relative parts of ruminal digested from apparent digested nutrients were measured with values between 78 and 88, 83 and 98, 93 and 97 as well as 88 and 100% respectively. PMID- 8512452 TI - [Ruminal nitrogen metabolism in calves and sheep. 3. Effect of hay-concentrate ratio in calves]. AB - During the milk feeding period (ca. 55th day of life) and 2 weeks after the milk feeding period (ca. 80th day of life) the influence of a hay quota in the ration (on DM basis) of 6, 10, 14 and 18% in the milk feeding period and of 16, 23, 31 and 37% in the period after milk feeding was tested as to ruminal N metabolization with calves supplied with duodenal re-entrant cannulae. The increase of the hay quota in the ration for ruminating calves reduced as a tendency duodenal NAN passage, its bacterial N-quota, post-ruminal NAN digestibility and, due to a worse utilization of available N for bacterial N synthesis, bacterial N-synthesis rate. The apparent fermentation of organic matter was, as a tendency, increased with the growing hay quota in the ration. PMID- 8512454 TI - [Energy metabolism of chicks at low environmental temperatures]. AB - The daily energy metabolism of growing chickens for meat production (origin T 82) fed ad libitum was measured from the 5th up to the 65th day of life at environmental temperatures decreasing in the course of development (25, 20, 15, 15, 15, 10, 10, 5 and 5 degrees C, resp.). Further in each period the heat production was measured through a wide range of temperatures (Maximum 40 degrees C to 5 degrees C in steps of 5 K) by 30-minute short time measurements. The mean live weight of the chickens was 75 g at the beginning of the experiment and 3416 g (male) or 2952 g (female) at the end of the experiment. The digestibility of energy and nutrients was independent of the stage of development. On average the total efficiency of utilization of metabolizable energy was 39.2 +/- 4.8% and the partial efficiency of utilization was 69.7 +/- 2.1%. 15-38% of the produced heat, caused by thermoregulation. The thermoneutral temperature decreased in the course of development from 35 to 18 degrees C and in the same way the thermoregulatory heat production decreased from 23 to 12 kJ/kg LW0.75.d.K. In the 2nd period the thermoregulatory heat production was extraordinarily high at an amount of 28 kJ/kg LW0.75.d.K. PMID- 8512453 TI - [Determination of endogenous N-excretion and nitrogen balance in the range of low N-intake in rats]. AB - The investigations were carried out in order to develop foundations for a complex growth model including the effect of N-efficiency mechanism first of all for the rat. Therefore N-balance trials with rats of different live weights were made using diets of equal protein quality. The curve of the regressively calculated N efficiency function courses relatively linear in its lower part, i.e. for low N intakes. The protein quality value "A.b" was proved to be constant for all investigated live weight ranges. In similar trials with different protein qualities was also found a linear course for low N-intakes. The regressively estimated N-maintenance requirement (for N-Intake = 0) related to metabolic live weight (NMR/LWkg0.67) amounts to 180 mg/d. In addition endogenous N-excretions were determined in 15N tracer experiments on animals of different live weight fed graduated amounts of a quality constant protein. The NMR-values (sum of endogenous excretions from faeces and urea) depend on the level of N-intake, i.e. they can not be considered as constant. The endogenous faecal N-loss related to metabolic live weight is relatively constant indeed, whereas the amount of endogenous urea N-loss is dependent on the level of N-intake. Therefore calculations based on the N-efficiency curve, e.g. amino acid requirement dependent on performance and prediction of N-deposition respectively, should not be carried out on the basis of "N-retention" (N-balance + NMR) but only on the basis of N-balance. PMID- 8512455 TI - Biogenic amines in silage. 1. The occurrence of biogenic amines in silage. AB - In laboratory silages made from orchardgrass, red clover and oats, significant levels of toxic biogenic amines were found. The most widespread were putrescine and cadaverine, concentrations of spermidine, spermine and histamine were ten times lower on average. Of the amines considered, putrescine content seems to be the most sensitive indicator of the extent of putrefaction in silages. A relationship between the putrescine contents and the degree of proteolysis was found. The biogenic amine content is closely connected with both the variety of crop ensiled and even more so with the method and the efficiency of preservation. Neither the application of formic acid nor wilting suppressed the formation of any of the amines in silages selectively. Formic acid suppressed the total concentration of amines to 23% as compared with controls. The highest levels of amines were found in orchardgrass and oat silages; smaller amounts were detected in clover silages. In the case of very poorly preserved silage 100-150 g of toxic amines can be consumed by a cow in a day. This could have a deleterious effect on the physiological condition and the performance of livestock. PMID- 8512456 TI - Biogenic amines in silage. 2. The dynamics of the formation of biogenic amines in silage. AB - When analysing a series of laboratory silages made from orchardgrass, red clover and oats, the fluctuating dynamics of biogenic amines were observed. For levels of putrescine and cadaverine, a rapid exponential increase culminating approximately 30-50 days after ensiling is typical. A small decrease, reaching the minimum at approximately the 100th day, is sometimes followed by a second increase in amine concentrations achieving its maximum approximately 200-230 days after ensiling. Irregular curves of the dynamics probably originate in the simultaneous decarboxylation and deamination reactions along with other relevant amine degradation processes. The dynamics of other biogenic amines-spermidine, spermine and histamine are more difficult to predict. The changes in histamine levels resembled those in the diamines. Some 200 days after ensiling, considerable increases in this toxic amine were observed. The dynamics of some quality criteria, especially the degree of proteolysis, were in many cases similar to those of the amines. PMID- 8512457 TI - XbaI polymorphism of the apolipoprotein B gene in patients with hyperlipidemia and echo-Doppler evidence of arterial lesions. AB - This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups. PMID- 8512458 TI - Long-term administration of probucol and QTc interval prolongation. AB - Electrocardiographic QTc intervals were measured in twenty-one hypercholesterolemic patients before and after long-term probucol (500-1,000 mg/day for 30 months) treatment. Probucol reduced serum total cholesterol (TC), triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C). Mean QTc interval prolongation after probucol was 17 msec. A positive correlation was found between the change in QTc interval after probucol (delta QTc) and the total amount of probucol administered. delta QTc was negatively correlated to the pre treatment QTc interval. No correlation was observed between serum probucol concentrations and delta QTc. Neither clinical evidence of cardiotoxicity nor critical arrhythmias were noted during the treatment period. PMID- 8512459 TI - Vitamin E: the evidence for an anti-atherogenic role. AB - Vitamin E is the major lipid-soluble antioxidant present in blood. It acts synergistically with other circulating and cellular antioxidants, to protect cells from damage and lysis induced by oxidative stress. Most of the vitamin E in blood plasma is present in the low density lipoprotein (LDL) fraction, hence it is optimally placed to prevent free-radical mediated modification of this lipoprotein. There is compelling evidence indicating that LDL oxidation, which occurs during atherogenesis and which is probably involved in lesion initiation and progression, is inhibited by vitamin E, and it has been proposed that vitamin E may be anti-atherogenic by virtue of its antioxidant properties alone. However recent studies suggest it may also act by other mechanisms. PMID- 8512461 TI - Report on breastfeeding in Dunedin Hospital's Neonatal Intensive Care Unit. PMID- 8512460 TI - Angiotensin II forming activity of vascular endothelial and smooth muscle cells. AB - To clarify the role of vascular endothelial cells (VEC) and smooth muscle cells (VSMC) in the generation of angiotensin (Ang) II, we measured the Ang II forming activity of these cells in culture using synthetic Ang I and tridecapeptide renin substrate (13RS). Angiotensin converting enzyme (ACE) activity was demonstrated in both types of cells, and the Ang I converting activity was highly sensitive to an ACE inhibitor. Both VEC and VSMC were able to generate Ang II from 13RS independently of ACE and renin. The activity was partially inhibited by chymostatin. It is suggested that Ang I could be converted to Ang II not only by VEC but also by VSMC. Both VEC and VSMC possess alternate Ang II forming pathways independent of ACE and renin. PMID- 8512462 TI - The identification and resolution of a clinical problem. PMID- 8512463 TI - Health beliefs and children--is it an illness or a normal life event? AB - Midwives' health beliefs related to childbirth are often the cause of conflict in the workplace. A review of the literature on the medical model and the normal life event model of childbirth demonstrates the divergence of these beliefs. The medical model considers childbirth an illness--the outcome is measured in perinatal and maternal mortality rates and the mother is a passive patient. The normal life event model considers childbirth a normal process--the outcome is measured in holistic terms and the mother is an active participant. PMID- 8512464 TI - Physical incompatibility of vancomycin and ceftazidime for intravitreal injection. PMID- 8512465 TI - Laser treatment of retinopathy of prematurity. PMID- 8512466 TI - Hyphema as a complication of adjustable suture surgery. PMID- 8512467 TI - Topical anesthesia in a patient with a history of retrobulbar hemorrhage. PMID- 8512468 TI - Ectodermal dysplasia, ectrodactyly, and clefting syndrome and bilateral retinal detachment. PMID- 8512469 TI - Giant-cell reaction in surgically excised subretinal neovascular membrane. PMID- 8512470 TI - Corneal graft rejection episode after excimer laser phototherapeutic keratectomy. PMID- 8512471 TI - Good syndrome and herpetic keratitis. PMID- 8512472 TI - Physicians not entirely responsible for rising health care costs. PMID- 8512473 TI - Supplemental vitamin A retards loss of ERG amplitude in retinitis pigmentosa. PMID- 8512474 TI - How shall research in the treatment of retinitis pigmentosa proceed? PMID- 8512475 TI - Cash flow management. AB - In the face of decreasing reimbursement and increasing expenses, careful cash flow management has assumed an increasingly important role in developing and maintaining a successful ophthalmology practice. Funds must be collected as promptly and efficiently as possible, and retained and invested until needed by the practice to pay expenses. Office collection techniques and suggestions for dealing with third-party payers are presented. Managed care contracting and the inherent risks involved are discussed. Advice on accounts payable management is provided, and suggestions for investment of idle funds are outlined. This information should allow the formulation of a practical plan to maximize profitability in each ophthalmology practice. PMID- 8512476 TI - A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. AB - OBJECTIVE: To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. DESIGN: Randomized, controlled, double-masked trial with 2 x 2 factorial design and duration of 4 to 6 years. Electroretinograms, visual field area, and visual acuity were measured annually. SETTING: Clinical research facility. PATIENTS: 601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria. Ninety-five percent of the patients completed the study. There were no adverse reactions. INTERVENTION: Patients were assigned to one of four treatment groups receiving 15,000 IU/d of vitamin A, 15,000 IU/d of vitamin A plus 400 IU/d of vitamin E, trace amounts of both vitamins, or 400 IU/d of vitamin E. MAIN OUTCOME MEASURE: Cone electroretinogram amplitude. RESULTS: The two groups receiving 15,000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage (P = .01). Among 354 patients with higher initial amplitudes, the two groups receiving 15,000 IU/d of vitamin A were 32% less likely to have a decline in amplitude of 50% or more from baseline in a given year than those not receiving this dosage (P = .01), while the two groups receiving 400 IU/d of vitamin E were 42% more likely to have a decline in amplitude of 50% or more from baseline than those not receiving this dosage (P = .03). While not statistically significant, similar trends were observed for rates of decline of visual field area. Visual acuity declined about 1 letter per year in all groups. CONCLUSIONS: These results support a beneficial effect of 15,000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa. PMID- 8512477 TI - Optic neuritis treatment trial. One-year follow-up results. AB - OBJECTIVE: To determine the efficacy of corticosteroids as treatment for acute demyelinative optic neuritis after completion of 1 year of patient follow-up in the Optic Neuritis Treatment Trial. DESIGN: Randomized placebo controlled multicenter clinical trial. SETTING: Fifteen university or hospital-based centers throughout the United States. PATIENTS: Four hundred fifty-seven patients with acute demyelinative optic neuritis between 18 and 46 years of age. INTERVENTION: Either intravenous methylprednisolone sodium succinate (250 mg every 6 hours) for 3 days followed by oral prednisone (1 mg/kg per day) for 11 days, oral prednisone (1 mg/kg per day) for 14 days, or oral placebo for 14 days. The first two regimens were followed by a short taper of corticosteroid therapy. MAIN OUTCOME MEASURES: Visual acuity, visual field, contrast sensitivity, and color vision. RESULTS: Visual acuity at 1 year was 20/40 or better in 95% of the placebo group, 94% of the intravenous group, and 91% of the oral prednisone group. Comparing each corticosteroid group with the placebo group, there were no statistically significant differences in the distributions of any of the four measures of visual function. Patients in the oral prednisone group suffered a higher rate of new attacks of optic neuritis than patients in either of the other two groups. CONCLUSIONS: The visual benefit from treating acute optic neuritis with intravenous followed by oral corticosteroids is short term, limited to an accelerated rate of recovery. The decision whether to prescribe this regimen for optic neuritis, or to prescribe no treatment, must be made for each patient on an individual basis. Oral prednisone alone, in the dose range used in the Optic Neuritis Treatment Trial, should not be prescribed. PMID- 8512478 TI - Validity and interpretation of Amsler grid reports. AB - OBJECTIVE: To compare the reports of scotomas and metamorphosia in standard and threshold Amsler grid testing with the location and extent of scotomas in the macular region as determined by standard and threshold fundus perimetry. DESIGN: Fundus perimetry determined the existence, size, and retinal location of macular scotomas. Amsler grid testing was performed with the scanning laser ophthalmoscope and the TA-300 system (Stereo Optical, Chicago, Ill). All testing was done at both standard and threshold light conditions. PATIENTS: Fifty-five patients with vision loss in the macular region and 10 normally sighted subjects. RESULTS: Nearly half of the standard and threshold scotomas were not detected by Amsler grid testing. For scotomas of 6 degrees or less in diameter, 77% of standard and 87% of threshold scotomas were not detected by Amsler grid testing. Of the eyes with central scotomas involving the fovea, 66% used an eccentric preferred retinal locus for fixating the center of the grid. Finally, more than half of the distortion reported in Amsler grids was at the retinal area that corresponded to the scotoma area, not a nonscotoma retinal area. CONCLUSION: Amsler grid reports have poor validity and cannot be accurately interpreted for use in the clinical diagnosis of retinal defects. PMID- 8512480 TI - Ocular injuries and diseases at a combat support hospital in support of Operations Desert Shield and Desert Storm. AB - A retrospective review of all emergency department visits to a combat support hospital (one of four combining to support 150,000 troops) during Operations Desert Shield and Desert Storm was conducted, and all medical records of patients with ocular complaints were analyzed. Ocular injury and/or disease accounted for 14% (108/767) of these visits to the emergency department. Of 108 patients with ocular complaints, corneal foreign bodies (18), ocular burns (14), and traumatic iritis (eight) were the most common injuries treated, while blepharitis and conjunctivitis (16) were the most common diseases. Nineteen (18%) of the 108 patients with ocular complaints were treated during support of the ground war in Iraq (13 were Iraqi prisoners). Ophthalmic injuries accounted for 13% (19/149) of all ground war casualties; however, eight individuals had associated injuries deemed more significant than those of ocular concern. This incidence continues the trend of earlier wars, which has demonstrated a steady increase in ocular injuries. Most US Army troops were issued protective goggles, but only three of 92 American patients wore them at the time of their injury and/or disease. PMID- 8512479 TI - Clinical subtypes of cone-rod dystrophy. AB - OBJECTIVE: To determine possible distinct phenotypic subtypes of cone-rod dystrophy. PATIENTS: Thirty-three patients with cone-rod dystrophy (from 25 families) were assessed prospectively on electroretinography, visual field testing, psychophysical threshold profiles, and fundus features. The clinical records of an additional 150 patients with cone-rod dystrophy were examined retrospectively in terms of the classification schema derived from the prospective study. RESULTS: Based on electroretinographic recordings, two major types of cone-rod dystrophy were differentiated. In type 1, cone amplitudes were reduced to a greater degree than were rod amplitudes on electroretinography, while in type 2, cone and rod electroretinographic amplitudes were reduced in equal proportion. These two types were further subdivided on the basis of patterns of visual field loss and threshold elevation. In type 1a, there was a central or paracentral scotoma, and cone thresholds were more elevated centrally than peripherally. In type 1b, there was no central scotoma, and cone thresholds were more elevated peripherally than centrally. In type 2a, there was a central scotoma, cone thresholds were more elevated centrally than peripherally, and rod thresholds were more elevated peripherally than centrally. In type 2b, a partial or complete ring scotoma was present, cone thresholds were more elevated peripherally than centrally, and rod thresholds were more elevated in the midperipheral than in either the central or far peripheral region of the retina. Of the 150 additional patients with cone-rod dystrophy, data sufficient for classification were available for 95 patients, and all but two had findings that were consistent with classification into one of these four subtypes. CONCLUSION: Our results identify four functionally distinct subtypes of cone-rod dystrophy that may be useful for patient counseling and future molecular genetic studies. PMID- 8512481 TI - Five-year corneal graft survival. A large, single-center patient cohort. AB - OBJECTIVE: To determine the survival rates and causes of secondary graft failure in a large, consecutive series of penetrating keratoplasties. DESIGN: All eyes undergoing penetrating keratoplasty at a single center were evaluated for factors relating to penetrating keratoplasty preoperatively, surgically, and postoperatively at 1, 3, 6, 9, 12, 18, and 24 months and then at yearly intervals. Since 1986, data analysis has been prospective. SETTING: A large, private practice, tertiary center for corneal disorders and surgery. PATIENTS: A consecutive series of 1819 penetrating keratoplasties performed from August 1982 through August 1990; 13 eyes with primary graft failure were excluded. MAIN OUTCOME MEASURE: Graft failure and causes of failure. Follow-up ranged from 1 to 96 months, with a mean of 26.6 months. RESULTS: Pseudophakic bullous keratopathy was the most common diagnosis necessitating keratoplasty (38.6%). Secondary failures occurred 111 times (6.1%). The 2- and 5-year survival rates for all grafts in the study were 95% and 91%, respectively. While endothelial failure as a result of immunologic allograft reactions was the most common cause of graft failure (27%), problems with the external surface of the graft caused nearly as many failures (25%). The risk of failure from surface-related problems was highest at 3 months after surgery. There were significantly decreased survival rates for grafts in eyes with regrafts (P < .0001), in eyes left aphakic at keratoplasty (P < .0001), and in eyes with deep stromal vascularization (P < .0001). CONCLUSION: Penetrating keratoplasty is a successful form of transplantation, and survival rates are gradually increasing. The risk of graft failure appears highest within the first year after transplantation. PMID- 8512482 TI - A screening test for integrative visual dysfunction in Alzheimer's disease. AB - OBJECTIVE: To develop a screening test to help ophthalmologists detect visually symptomatic patients with as yet undiagnosed Alzheimer's disease. DESIGN: Administration of a battery of tests consisting of items modified from existing psychometric materials to decrease examination time and increase ease of scoring. PARTICIPANTS: Fourteen patients with Alzheimer's disease and prominent visual symptoms; 53 control subjects matched to the patients with Alzheimer's disease for age, sex, and educational level; and 22 patients with subnormal visual acuity or visual fields who did not have Alzheimer's disease. RESULTS: The novel battery of tests distinguished all 14 visually symptomatic patients with Alzheimer's disease from patients without Alzheimer's disease and control subjects. CONCLUSION: This battery of tests should enhance the ophthalmologic detection of Alzheimer's disease. PMID- 8512483 TI - Radiotherapy in the management of thyroid orbitopathy. Computed tomography and clinical outcomes. AB - OBJECTIVE: We investigated the long-term outcome of patients with thyroid orbitopathy treated with orbital radiotherapy using quantitative clinical measurements and orbital computed tomographic morphometric changes. DESIGN: Patients who had undergone orbital radiotherapy for thyroid orbitopathy at least 1 year previously were retrospectively recalled for follow-up examination and computed tomography. Controls were patients with similar disease activity but who had not undergone radiotherapy. SETTING: Subspecialty clinic in a university teaching hospital. PATIENTS: Twenty-one patients (42 orbits) who underwent radiotherapy and six clinically comparable patients who had not undergone radiotherapy (12 orbits). INTERVENTION: Standardized, super-voltage, orbital radiotherapy. MEASUREMENTS: Five clinical indexes of orbitopathy and six computed tomographic indexes were examined for interval changes. RESULTS: The orbital computed tomographic muscle-diameter index enlargement ratio did not change in either group (radiotherapy group, 1.54 to 1.51, not significant; nonradiotherapy group, 1.37 to 1.36, not significant). The mean (+/- SEM) number of muscles with low-density areas increased in both groups (radiotherapy group, 1.1 [+/- 1.9] muscles per orbit; P < .001). Soft-tissue signs improved significantly with lesser improvements in extraocular muscle function in both groups. Proptosis, visual acuity, and intraocular pressure rise on upgaze did not improve significantly in either group. CONCLUSIONS: No changes in muscle size measured with computed tomography were found in either patients undergoing radiotherapy or patients not undergoing radiotherapy after long-term follow-up. Clinical indexes of thyroid orbitopathy, especially soft-tissue signs, improved on follow-up, but this was not influenced by the method of treatment. PMID- 8512484 TI - Long-term effects of mitomycin on filtering blebs. Lack of fibrovascular proliferative response following severe inflammation. AB - BACKGROUND AND OBJECTIVE: The use of antimetabolites, such as fluorouracil and mitomycin, enhances the success rate of filtering surgery, especially in eyes at high risk for failure, and increases the likelihood of a thin, avascular filtering bleb. In addition, mitomycin may cause long-term inhibition of the fibroblast's ability to proliferate in the conjunctiva and Tenon's capsule. Preoperative and postoperative inflammation frequently contributes to scarring of filtering blebs. The purpose of this study is to evaluate the effect of intraoperative mitomycin use on the survival of filtering blebs after severe inflammation. DESIGN: We retrospectively studied three eyes that had undergone trabeculectomy with intraoperative mitomycin. Two eyes had concomitant intraocular lens implantation. All three eyes had blebs that functioned well postoperatively. PATIENTS: These eyes sustained episodes of intense inflammation in the form of herpes zoster ophthalmicus, endophthalmitis, or purulent infection of the bleb postoperatively. RESULTS: Following treatment of the inflammation, no change in the appearance or function of the bleb could be detected. CONCLUSION: Either the indirect effect of mitomycin in producing a thin, avascular bleb or a long-term effect of mitomycin on the ability of conjunctival and Tenon's capsule fibroblasts to proliferate may have contributed to bleb survival. PMID- 8512485 TI - Treatment of chronic postfiltration hypotony by intrableb injection of autologous blood. AB - OBJECTIVE: To treat chronic hypotony with decreased vision after filtration surgery. DESIGN: After observation from 3 1/2 to 13 months with no spontaneous improvement, eyes were treated with the experimental therapy and followed up closely to determine the results. PATIENTS: Four eyes with chronic hypotony, selected from a series of 125 eyes receiving trabeculectomy augmented by intraoperative mitomycin. All eyes had posterior chamber pseudophakia. All eyes had postoperative laser cutting of sutures holding the scleral flap of the trabeculectomy. INTERVENTION: After administration of topical prophylactic 0.3% ciprofloxacin hydrochloride and topical anesthetic, the bleb was inflated with whole autologous blood through a 27-gauge needle passed subconjunctivally into the bleb. MAIN OUTCOME MEASURES: Change in intraocular pressure, change in vision, change in choroidal detachment, any type of complication. RESULTS: Average intraocular pressure increased from 5.5 to 8.2 mm Hg. Average vision improved from 20/148 to 20/33. In two eyes with choroidal detachment, the detachment absorbed in one eye and decreased in the other. No complications occurred. CONCLUSION: Intrableb injection of autologous blood deserves further study as a possible treatment for hypotony following filtration. PMID- 8512486 TI - The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group. AB - OBJECTIVE: To develop the Lens Opacities Classification System III (LOCS III) to overcome the limitations inherent in lens classification using LOCS II. These limitations include unequal intervals between standards, only one standard for color grading, use of integer grading, and wide 95% tolerance limits. DESIGN AND RESULTS: The LOCS III contains an expanded set of standards that were selected from the Longitudinal Study of Cataract slide library at the Center for Clinical Cataract Research, Boston, Mass. It consists of six slit-lamp images for grading nuclear color (NC) and nuclear opalescence (NO), five retroillumination images for grading cortical cataract (C), and five retroillumination images for grading posterior subcapsular (P) cataract. Cataract severity is graded on a decimal scale, and the standards have regularly spaced intervals on a decimal scale. The 95% tolerance limits are reduced from 2.0 for each class with LOCS II to 0.7 for nuclear opalescence, 0.7 for nuclear color, 0.5 for cortical cataract, and 1.0 for posterior subcapsular cataract with the LOCS III, with excellent interobserver agreement. CONCLUSION: The LOCS III is an improved LOCS system for grading slit-lamp and retroillumination images of age-related cataract. PMID- 8512487 TI - Chronic Nocardia asteroides endophthalmitis after extracapsular cataract extraction. AB - A 65-year-old man underwent an uncomplicated extracapsular cataract extraction with placement of a posterior chamber intraocular lens. The patient developed delayed-onset chronic endophthalmitis caused by Nocardia asteroides. This was confirmed on multiple intraocular cultures, as well as histopathologic examination of the lens capsular bag. The patient was treated with periocular, intravitreal, and systemic antibiotic treatment, combined with intraocular lens removal, total capsulectomy, and three vitrectomies in an attempt to eradicate the organism and calm the eye. The patient went on to develop widespread endophthalmitis that required enucleation of the infected globe. To our knowledge, this is the first case of delayed-onset chronic endophthalmitis caused by N asteroides after extracapsular cataract extraction with a posterior chamber intraocular lens. PMID- 8512488 TI - Multifocal fibrosclerosis. Report of a case of bilateral idiopathic sclerosing pseudotumor and retroperitoneal fibrosis. AB - We describe a 56-year-old white man who presented with gradual and progressive visual loss and subsequent hypertension and pedal edema. A computed tomographic scan of the orbits showed bilateral diffuse retrobulbar masses, and an abdominal computed tomographic scan showed a diffuse retroperitoneal mass invading the aorta, ureters, and inferior vena cava. Biopsies of the orbit and abdomen confirmed a heterogeneous cell population and marked fibrosis consistent with a sclerosing inflammatory process. Bilateral sclerosing orbital inflammatory disease should cue the physician to suspect coexisting systemic disease. This report is the fourth to document bilateral sclerosing orbital inflammatory disease and the second to have obtained biopsies of the orbit and abdomen showing histologic similarities. PMID- 8512489 TI - Pharmacologic induction of posterior vitreous detachment in the rabbit. AB - OBJECTIVE: To assay the proteolytic activity of plasmin on the vitreoretinal junction and to assess a potential facilitating effect on posterior vitreous detachment. METHODS: We injected 1 U of plasmin into the vitreous of rabbits. Some eyes underwent vitrectomy after plasmin injection. Electroretinography and electron microscopy were performed. RESULTS: In plasmin-treated eyes, electroretinography displayed a transient (3 days) decreased b-wave amplitude. Histologic examination demonstrated posterior vitreous detachment in eyes that received intravitreal plasmin followed by vitrectomy. CONCLUSION: Plasmin may prove to be a useful biochemical adjunct to mechanical vitrectomy. PMID- 8512490 TI - Photodynamic therapy of subretinal neovascularization in the monkey eye. AB - Experimental subretinal neovascularization in the monkey eye was treated by photodynamic therapy with rose bengal. Following intravenous injection of rose bengal, the subretinal vessels were irradiated with filtered light. Successful treatment was achieved, provided the subretinal vessels were irradiated during the period in which the dye was present in and around the subretinal vessels but had already cleared from the retinal vasculature. The successfully treated lesions demonstrated replacement of the leaking and pooling subretinal vessels with a non-leaky scar. Morphologic evaluation revealed immediate destruction of the subretinal plexus, with minimal damage to the overlying retina. The destroyed subretinal tuft was replaced by a scar containing mainly fibroblasts embedded in collagen fibers. Our results suggest that photodynamic therapy is potentially useful for destruction of subretinal vessels without damaging the overlying retina. PMID- 8512491 TI - Scleritis resembling a scleral buckle. PMID- 8512492 TI - Apocrine hidrocystoma of the eyelid. PMID- 8512493 TI - Optic nerve sheath fenestration through a lateral canthotomy incision. AB - Optic nerve sheath fenestration is an increasingly useful surgical technique for relief of visual loss due to a number of optic disc pathologic conditions. To date, surgeons have employed either a medial approach with disinsertion of the medial rectus muscle or a lateral approach with removal of the lateral orbital rim to gain access to the retrobulbar optic nerve. We report herein a technique for approaching the optic nerve through a lateral canthotomy incision that does not require removal of bone or disinsertion of an extraocular muscle. It has been used to provide ready surgical exposure of the optic nerve in 17 eyes of 14 patients. This technique combines the advantages of lateral exposure of the optic nerve with an ease of operation similar to that of the medial approach. PMID- 8512494 TI - Interlocking Crawford triangles in frontalis suspension. AB - In Crawford's pattern of frontalis suspension, two bands are passed, one nasally and the other temporally, forming two base-down triangles with their apexes attached at the brow incisions. Over time, opposing vector forces in the center of the eyelid can cause "cheese-wiring" of the bands with resultant shortening of the inferior bases of both triangles and loosening of the suspensory loops. We modified the standard pattern by interlocking the bands centrally in the lid. A mathematical model was developed that demonstrates neutralization of these opposing forces, resulting in a symmetrical and flexible redistribution of the lifting forces. In support of this mathematical model, a retrospective analysis of 42 consecutive cases using this technique revealed good aesthetic results in terms of lid height, contour, and symmetry, with no important complications from this modification. PMID- 8512495 TI - Genetic polymorphism of alcohol and aldehyde dehydrogenase and the effects on alcohol metabolism. AB - Influence of genetic polymorphism at the alcohol dehydrogenase2 (ADH2) and aldehyde dehydrogenase2 (ALDH2) loci on ethanol elimination and blood acetaldehyde level was studied in healthy subjects. Polymorphic regions of the ADH2 and ALDH2 genes were amplified for genomic DNA by using the technique of polymerase chain reaction. The ADH2 genotype was determined by digestion with the restriction enzyme MaeIII and the ALDH2 genotype was defined by hybridization with sequence specific oligonucleotide probes. Both loci were typed for unrelated 58 individuals by using the above methods. The gene frequencies of each locus were estimated as follows; 0.31 and 0.69 for ADH2*1 and ADH2*2, respectively, and 0.73 and 0.27 for ALDH2*1 and ALDH2*2, respectively. These values were consistent with the Hardy-Weinberg equilibrium. Pedigree analysis of 6 families with 46 subjects on both loci confirmed Mendelian inheritance. In order to investigate differences in ethanol elimination among ADH2 and ALDH2 genotype groups, 0.4 g/kg body weight of ethanol was administered to 93 subjects whose genotypes of both loci were determined by the above methods and blood ethanol and acetaldehyde levels were measured. None of the subjects homozygous for the ALDH2*1 allele showed facial flushing and any increase in blood acetaldehyde level. All the homozygotes and heterozygotes with the ALDH2*2 allele exhibited facial flushing, and the former showed a marked increase in blood acetaldehyde level and the latter did a mild increase. On the other hand, the influence of the ADH2 genotype on blood acetaldehyde level was not significant. The values of Widmark's beta 60 (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed significant differences among the three groups of the ALDH2 genotypes in each group of the three ADH2 genotypes, and in decreasing order of both the values were ALDH 2*1/*1, ALDH2*1/*2, ALDH2*/*2, However, there were no significant differences in the values among the ADH2 genotypes. PMID- 8512496 TI - [Alcohol consumption and brain adenylate cyclase system in rats: brain adenylate cyclase activity in alcohol-preferring AA and alcohol-avoiding ANA rats]. AB - Brain adenylate cyclase (AC) activity in the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats was examined. Both basal and Gpp(NH) p-stimulated AC activities were higher in the cerebral cortex of the ANA rats than in the AA rats. Isoproterenol-stimulated AC activity tended to increase in the cerebral cortex of the ANA rats compared to the AA rats. Basal AC activity in the striatum of the AA rats was higher than that in the ANA rats, however, striatal Gpp(NH)p-stimulated AC activity was not different between the two rats lines. In the mesolimbic and cerebellum, there was no difference in AC activity between the rat lines. These results suggest that the noradrenergic function in the cerebral cortex has an important role in the regulation of alcohol intake. PMID- 8512497 TI - Keep Medicare healthy. In the bad old days before Medibank. PMID- 8512498 TI - I wish to be a nurse. PMID- 8512499 TI - Prescribed health. PMID- 8512500 TI - Straight to the Point. ANF HIV/AIDS video in Berlin festival. PMID- 8512501 TI - HIV/AIDS: Medicare is the key to care. PMID- 8512502 TI - Evaluation of the diagnostic accuracy of MR imaging at 0.3 T, based on clinical follow up of 3262 examinations. AB - The results of 4504 0.3 T magnetic resonance (MR) examinations, of which 3262 had clinical follow up are described. The overall true positive rate of MR imaging was 72%, with a range of 69-100%. While the best results were obtained for evaluation of spinal cord syrinx and normal cerebral examinations, 31% of patients with cerebral demyelination were incorrectly diagnosed. The false positive rate was relatively low (3-5% in most cases), but a significant 17% of patients considered to have normal cerebral examinations were later shown to have pathology. While the true positive rate of magnetic resonance imaging was greater than that of the suspected clinical diagnosis (37% correct), the results of this assessment at 0.3 T are significantly poorer than those previously published at 1.5 T. PMID- 8512503 TI - Cavernous haemangiomas (angiomas) of the brain: clinically significant lesions. AB - A review of 2000 consecutive magnetic resonance imaging (MRI) brain studies identified 18 (0.9%) patients with lesions that satisfied MRI criteria for cavernous haemangiomas. The clinical, computed tomography (CT) and MRI findings in 23 patients with probable cavernous haemangiomas were compared. Thirty-three lesions were identified with multiple lesions in five (22%) patients. In 19 (82%) patients the neurological presentation corresponded to a cavernous haemangioma. The presenting symptoms were: seizures in 11 patients (48%); progressive neurological symptoms and signs in four (17%); and acute symptoms and signs due to haemorrhage in four (17%). T2 weighted images suggested the diagnosis in all cases, with 24 (73%) lesions showing the typical appearance of an area of mixed signal intensity with a rim of low signal intensity. In the absence of acute haemorrhage, CT demonstrated well circumscribed, round or oval hyperdense lesions without significant mass effect and with normal surrounding brain tissue in the majority of cases. Although not diagnostic, these CT features are strongly suggestive of cavernous haemangiomas. PMID- 8512504 TI - Perimesencephalic subarachnoid haemorrhage: negative angiography and favourable prognosis. AB - The computed tomography (CT) scans of 110 consecutive patients who presented, over a 4.5-year period, following spontaneous subarachnoid haemorrhage (SAH), were reviewed. All 110 patients also had one or more 4-vessel digital subtraction cerebral angiograms. The CT scans were reviewed in each case without knowledge of the angiographic result. In nine patients (8%), SAH was confined to the perimesencephalic area, interpeduncular cistern and/or prepontine region at CT. All nine patients had at least two, and some as many as four, negative cerebral angiograms. Eighteen of the 110 patients (16%) ultimately had negative angiography. Hence, the patients with isolated perimesencephalic haemorrhage (PMH) accounted for 50% of the negative angiograms. There was a significant association between isolated PMH and negative angiography (chi 2 = 50.1, P < 0.005). The specificity of PMH for negative angiography was 100% (95% confidence interval (CI) = 97-100%) and the sensitivity of PMH for a negative study was 50% (95% CI = 16-84%). Six of the 110 patients had basilar artery aneurysms demonstrated angiographically as the cause of their SAH but none of these six had isolated PMH at CT. All patients with isolated PMH were alive and well at follow up and none had suffered repeat SAH or vasospasm-related ischaemic cerebral injury. Perimesencephalic haemorrhage should be distinguished from SAH in general, because of the good prognosis associated with it and the doubtful need for repeat cerebral angiography after an initial negative study. PMID- 8512505 TI - Magnetic resonance imaging of central nervous system haemorrhage. AB - The variable magnetic resonance imaging appearances of central nervous system haemorrhage, both intra- and extra-axial, are described. These will vary with the type of image contrast (T1 or T2 weighting), the nature of the imaging sequence (spin-echo or gradient-echo) and the time from onset of haemorrhage. Magnetic resonance imaging is a useful technique for imaging haemorrhage in the central nervous system as it yields temporal information about haematoma development, and it is the only non-invasive means of imaging intraspinal haemorrhage. It is, however, limited in the imaging of haematomas within 24 h of onset and in subarachnoid haemorrhage where computed tomography is the investigation of choice. PMID- 8512506 TI - Carotid colour Doppler. AB - Following the introduction of a carotid colour duplex Doppler service, a retrospective survey of the second 100 patients examined was undertaken to determine the accuracy of the examination compared with angiography and surgery, and to assess the clinical efficacy of the results with a review of the final diagnosis, how that diagnosis was achieved and whether the test had helped assess the patient's illness or altered the medical management and/or the outcome of the patient's illness. The results indicated the expected accuracy of over 94% and that the examination helped assess the patient's illness in 92%, altered the management plan in 40% and altered the outcome of the patient's illness in 14% where the disease prevalence was 16%. PMID- 8512507 TI - Assessment of abdominal lymph nodes in a normal paediatric population: an ultrasound study. AB - During a 9 month period, 50 consecutive children were evaluated by ultrasound to determine the size, location (mesenteric vs para-aortic), number, shape and texture of abdominal lymph nodes in a normal paediatric population. High resolution linear array transducers were used with graded compression. Nodes ranging from 10 to 20 mm were recorded in the majority of subjects. In all cases mesenteric lymph nodes were larger and more numerous than para-aortic nodes. Para aortic lymph nodes were not seen in isolation. PMID- 8512508 TI - Alcohol sclerotherapy of simple parenchymal liver cysts. AB - Three symptomatic non-parasitic liver cysts in three patients were treated by the technique of percutaneous aspiration followed by sclerosis of the cyst lining by irrigation with absolute alcohol. In two patients the treatment was fully successful, with partial success in the third case. Two cysts underwent two separate treatments. The technique, which is reviewed, was shown to be a safe and effective alternative to conventional surgical management. PMID- 8512510 TI - Computed tomography pelvimetry: accuracy and radiation dose compared with conventional pelvimetry. AB - Several publications in the past few years have indicated that computed tomography (CT) pelvimetry is preferable to conventional pelvimetry when considering accuracy and radiation dose. Many of the previous publications have, however, compared state of the art CT pelvimetry with outmoded conventional pelvimetry techniques. This study compared both the accuracy and the radiation dose of CT pelvimetry with conventional pelvimetry as practised in two large teaching obstetric hospitals in Melbourne. The study did not demonstrate any significant difference in the accuracy between the two methods. The radiation dose to the fetal gonads was also similar. The radiation dose using CT pelvimetry could be significantly lowered if the axial CT section through the ischial spines were excluded from the CT technique. PMID- 8512509 TI - Sonographic detection of pneumoperitoneum: an experimental and clinical study. AB - The sonographic appearance of intraperitoneal air collection has been studied in 46 patients. In 30 patients (group I), a pneumoperitoneum had been iatrogenically induced either during aspiration of ascitic fluid or during laparoscopy. Three normal volunteers (group II) had been subjected to graded intraperitoneal air injection to quantify the smallest amount of air detectable by ultrasound (US). In eight patients (group III) the sonographic demonstration of free intraperitoneal air led to a diagnosis of hollow visceral perforation; whereas in another five patients (group IV) the sonographic findings reinforced the clinical suspicion of a 'sealed off' perforation in the presence of negative roentgenograms. In all patients intraperitoneal air was seen as an echogenic line with a posterior reverberation or ring down artefact. In patients with free air, this was best seen in the perihepatic spaces with the patient in the supine, left lateral decubitus or prone position. As little as 5 mL of air could be consistently detected in all three volunteers (group II). Artefacts leading to a pseudopneumoperitoneum on US included; (i) the artefacts distal to an overlying rib; (ii) ring-down artefact from air in the adjacent lungs; and (iii) hepatodiaphragmatic interposition of colon. With proper sonographic technique and principles of interpretation these can be distinguished from true intraperitoneal air. Although sonography may be more informative than conventional radiology in patients with hollow visceral perforation, we did not find it more sensitive than conventional roentgenograms in detecting free intraperitoneal air. Sonography, however, is distinctly superior in patients with a sealed off perforation in whom conventional roentgenograms are frequently negative. PMID- 8512511 TI - Breast cysts: pitfalls in sonographic diagnosis. AB - Ultrasound examination of the breast is extensively carried out to differentiate cystic from solid masses. Ten atypical cysts are presented that do not fulfil all the criteria for the ultrasonic diagnosis of breast cysts. These had internal echoes and some showed irregular contours or diminished through transmission. Diagnostic aspiration confirmed the cystic nature of these lesions. None showed cytologic evidence of malignancy or haemorrhage. The purpose of this paper is to bring this entity to the attention of radiologists so that echogenic cysts are considered in the differential diagnosis of well defined, solid appearing breast masses seen on ultrasound. PMID- 8512512 TI - The role of ultrasound and computed tomography in the evaluation of parotid masses. AB - A prospective sonographic study of 40 patients with symptomatic parotid masses detected all of their 48 lesions (sensitivity 100%). Computed tomography (CT) detected 47 lesions (sensitivity 97.5%). Ultrasound correctly characterized all benign tumours and inflammatory lesions and four out of five malignant tumours. Deep compartment involvement was accurately delineated in 10 (25%) patients but in two patients the extraparotid tumour origin could only be detected by CT. Ultrasound is a sensitive, non-invasive investigation of parotid masses. Computed tomography (CT) or magnetic resonance should be reserved for lesions that involve the deep compartment of the gland and cannot be separated from the parapharyngeal space or skull base. PMID- 8512513 TI - 24 hour/3 hour radio-uptake technique for differentiating degenerative and malignant bony lesions in bone scanning. AB - Differentiating bony metastases from degenerative lesions is of great importance to the oncologist. Routine bone scanning using technetium-99m methylene diphosphonate is the investigation of choice for detecting bony lesions, but its specificity is low. Using the difference in radio-uptake behaviour of metastatic and degenerative lesions as the criterion, a 24/3 h radio-uptake, lesion to non lesion ratio was used to separate out the two types of lesions. Radio-uptake ratio (RUR) distribution curves of malignant and degenerative lesions were found to be significantly different (P < 0.001). Taking 1.12 as the critical point, RUR of malignant lesions was found to be more than the critical point, and that of degenerative lesions was found to be less than the critical point. Sensitivity, specificity and accuracy were found to be 68%, 80% and 74%, respectively. PMID- 8512514 TI - Design of a radiology request/referral form. AB - A radiology/referral form has been designed and is offered as a basis for modification to meet the specific requirements of any department. The new form elicits more information, is ergonomically superior to the one it replaced, is designed to increase compliance in the completion of all relevant sections by the referring clinician and fulfils an educative function. PMID- 8512515 TI - Post-orchiectomy management in stage I testicular seminoma: elective irradiation or surveillance? AB - Fifty-six patients with stage I testicular seminoma were treated at this institute between January 1982 and December 1988. Post-orchiectomy elective radiotherapy to ipsilateral iliac-inguinal and para-aortic lymph nodes was delivered in 54 cases. An overall 3 year survival rate of 96% was observed in this series. Four patients (7%) relapsed (one junctional recurrence in iliac node region, two mediastinal/hilar nodes and one skeletal metastasis). Salvage chemotherapy proved successful in two out of three cases with nodal relapse. No dose limiting acute or late radiation related complications were noticed. No definite correlation was found between the patients who relapsed and various known adverse prognostic factors. We recommend elective irradiation of the draining lymph nodes in stage I seminoma, particularly at centres where surveillance is not feasible. PMID- 8512516 TI - A simplified puncture technique to reduce contamination with bodily fluids. AB - A simplified method of percutaneous wire placement is described, designed to decrease the amount of aerosol or spurting bodily fluids associated with wire placement. The technique involves minor modification of standard puncture techniques without the use of additional equipment. The technique has been successfully used in 22 patients and there have been no complications associated specifically with this technique. PMID- 8512517 TI - Cuff expander eases enema tip assembly. AB - Some barium enema kits are manufactured with two-part enema tips, enabling a cuff to be placed on the tip only if required. Difficulty can be experienced during enema tip assembly while attempting to place the cuff on the tip. A readily available gadget used in the farming sector provides a neat and cost-effective solution to this problem. PMID- 8512518 TI - Direct communication between the right pulmonary artery and the left atrium: magnetic resonance findings. PMID- 8512519 TI - Extrahepatic portal vein aneurysm in non-cirrhotic portal fibrosis. PMID- 8512520 TI - Treatment of fibromuscular hyperplasia of the external iliac artery by percutaneous transluminal angioplasty. PMID- 8512521 TI - Cerebral hydatid disease. AB - Although hydatid disease of the liver and lungs is common in South Asia, involvement of the brain is relatively rare. Two cases of cerebral echinococcosis are presented. One case involved the brain, kidney, heart and spleen. The case is unusual because of the multiplicity of intracranial lesions and sparing of the liver and lungs. The other case is a classical cerebral hydatid cyst. Both cases were confirmed histologically. PMID- 8512522 TI - Waiting lists for radiation therapy. PMID- 8512523 TI - John Langworthy Fuller (1910-1992). PMID- 8512524 TI - Steven G. Vandenberg (1915-1992). PMID- 8512525 TI - Genetics and alcoholism. July 1-2, 1992, Boulder, Colorado. Symposium proceedings. PMID- 8512526 TI - The D2 dopamine receptor gene: a review of association studies in alcoholism. AB - Following our initial observation that the Al allele of the D2 dopamine receptor (DRD2) gene was associated with alcoholism, a number of studies, both in the United States and abroad, have attempted to replicate and extend this finding in different Caucasian populations. In nine independent studies containing a total of 491 heterogeneous alcoholics (less severe and severe) and 495 heterogeneous controls (assessed and unassessed for alcoholism), the prevalence of the Al allele was 43.0% in the former group compared to 25.7% in the latter group (odds ratio = 2.18, p < 10(-7)). The prevalence of the Al allele increased to 56.3% in a more homogeneous sample of 158 severe alcoholics (odds ratio = 3.32, p < 10( 8)). Moreover, the Bl allele of the DRD2 gene was also found to be significantly associated with severe alcoholism. Additional data are accruing which also implicate the DRD2 Al and Bl alleles in substance use disorders other than alcoholism. If further studies continue to support the results currently at hand, they would indicate that the DRD2 gene is the most prominent single gene determinant of susceptibility to severe substance abuse. However, the larger role still appears to be played by a combination of environmental factors and as yet unidentified genes. PMID- 8512527 TI - Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. AB - The alcohol-flush reaction occurs in Asians who inherit the mutant ALDH2*2 allele that produces an inactive aldehyde dehydrogenase enzyme. In these individuals, high blood acetaldehyde levels are believed to be the cause of the unpleasant symptoms that follow drinking. We measured the alcohol elimination rates and intensity of flushing in Chinese subjects in whom the alcohol dehydrogenase ADH2 and ALDH2 genotypes were determined. We also correlated ADH2, ADH3, and ALDH2 genotypes with drinking behavior in 100 Chinese men. We discovered that ADH2*2 and ADH3*1, alleles that encode the high activity forms of alcohol dehydrogenase, as well as the mutant ALDH2*2 allele were less frequent in alcoholics than in controls. The presence of ALDH2*2 was associated with slower alcohol metabolism and the most intense flushing. In those homozygous for ALDH2*1, the presence of two ADH2*2 alleles correlated with slightly faster alcohol metabolism and more intense flushing, although a great deal of variability in the latter was noted. PMID- 8512528 TI - Genomic imprinting: implications for behavioral genetics. AB - In recent years it has become apparent that the parental origin of genetic material has an impact on gene expression and this effect has become known as genomic imprinting. The evidence for the influence of genomic imprinting on behavior and in the etiology of certain neurobehavioral disorders is discussed. The possibilities for a role for genomic imprinting in the inheritance of behaviors related to alcohol abuse and alcoholism and in the paternal alcohol syndrome are also explored. PMID- 8512529 TI - Why there is no gene for alcoholism. AB - The search for and recognition of biological and genetic markers of alcoholism are discussed in the context of a heuristic model of human alcoholism as a complex, multilocus, heterogeneous disorder. Implications of this model for the interpretation of results from both linkage and association studies are presented. PMID- 8512531 TI - Selective breeding for alcohol withdrawal severity. AB - Mouse lines have been genetically selected to be alcohol Withdrawal Seizure Prone (WSP) or Resistant (WSR). The selection index is the severity of withdrawal handling-induced convulsions seen after removal of mice from chronic exposure to ethanol vapor. Behavioral, pharmacological, and neurochemical results from a replicated bidirectional selection project are reviewed. In reciprocal F1 crosses of the WSP and WSR lines, substantial dominance for resistance to withdrawal was found in both replicated sets of lines. WSP and WSR mice differ principally, and markedly, in traits related to the severity of withdrawal from alcohols and other drugs with depressant properties. This suggests that genes influencing severity of withdrawal from chronic ethanol exposure also pleiotropically influence genetic susceptibility to dependence on other drugs of abuse. However, the results of WSP vs. WSR comparisons for traits related to ethanol sensitivity and tolerance development suggest control in large part by genes different from those influencing withdrawal severity. PMID- 8512530 TI - Selective breeding for initial sensitivity to ethanol. AB - Selective breeding for initial sensitivity to ethanol has been carried out by a number of investigators in order to investigate the mechanisms by which ethanol brings about a myriad of effects on the mammalian central nervous system. In addition the availability of these selectively bred animals provides clues to the causes of the genetic predisposition of humans to alcoholism. Eventually it is envisioned that the synteny between the mouse and human genomes will allow identification of specific genes responsible for acute effects of ethanol in both species as well as clues as to how alcoholism in humans can be better identified, prevented, and treated. PMID- 8512532 TI - Selective breeding, congenic strains, and other classical genetic approaches to the analysis of alcohol-related polygenic pleiotropisms. AB - Dimensions of behavioral sensitivities to alcohol in mice are under control of polygenic systems of relatively small size. The mode of inheritance of these phenotypes is frequently additive, with no evidence of dominance, epistasis, or sex linkage. The utility of classical breeding methodologies, such as selection, for assessment of genetic correlations is reviewed. A distinction is drawn between pleiotropisms in these polygenic systems, and the statistical concept of a genetic correlation. Development of congenic strains is argued to be a powerful alternative methodology, heretofore unused in alcohol pharmacogenetics. Using the phenotype of behavioral activation produced by a low dose of ethanol, we describe the production of an activated congenic strain on the non-activated background of the C57BL/6 mouse strain. Through five generations of repeated backcrossing, from a genetically heterogenous stock, "activational" alleles are being successfully transferred to the C57BL/6 background. Theoretical issues in the creation of congenic strains in potentially polygenic systems are covered, including number of effective loci and heritability. PMID- 8512533 TI - Quantitative trait loci (QTL) analyses and alcohol-related behaviors. AB - Recombinant inbred (RI) strains can make an important contribution toward the merger of molecular genetics and quantitative genetics in the quest for quantitative trait loci (QTL). We present preliminary analyses of alcohol-related processes from our ongoing research using the BXD RI series. Issues concerning reliability, genetic correlations, and RI QTL analysis are discussed. Several strategies for replication and extension of QTL candidate regions are considered: F1 crosses between RI strains, F2 crosses, heterogeneous stock, interspecific backcrosses, QTL selection, and the use of murine QTL in chromosomal regions syntenic to human chromosomes as candidate chromosomal regions for human QTL. PMID- 8512535 TI - Genetics, systems, and alcohol. AB - Under a variety of rubrics (e.g., complexity, self-constructing systems, dissipative structures), interest has recently burgeoned in applying principles of complex systems to a wide variety of scientific issues. A major concern is with emergent properties of systems not derivable from the properties of components of the systems. In this paper, some elementary aspects of "systems" considerations are applied to phenomena of alcohol pharmacogenetics. It is likely that whole new families of informative phenotypes can be generated by this approach. PMID- 8512534 TI - Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice. AB - Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach. PMID- 8512536 TI - Emotion and two kinds of meaning: cognitive therapy and applied cognitive science. AB - The clinical cognitive approach assumes that emotional reactions are mediated through the meanings given to events. Cognitive therapy aims to change emotion by changing meanings. It focuses on specific level meanings, evaluating the truth value of particular beliefs. Bower's science-driven associative network theory of cognition and emotion is also primarily concerned with specific meanings. This focus on meaning at a specific level causes problems, e.g. the contrasts between 'intellectual' and 'emotional' belief, between 'cold' and 'hot' cognition, and between explicit and intuitive knowledge. These problems are resolved in the Interacting Cognitive Subsystems (ICS) approach. ICS distinguishes between a specific and a more holistic, intuitive, level of meaning. In contrast to alternative approaches, ICS suggest that holistic level meanings are of primary importance in emotion production. Representations at this level consist of schematic mental models, encoding high-order inter-relationships and prototypical patterns extracted from life experience. The ICS approach to meaning is described and its implications for understanding and treating emotional disorders discussed, together with relevant empirical findings. ICS suggests a therapeutic focus on holistic rather than specific meanings, a role for 'non-evidential' interventions, such as guided imagery, and a rational basis for certain experiential therapies. PMID- 8512537 TI - The etiology of fear of heights and its relationship to severity and individual response patterns. AB - The acquisition of fear of heights in an undergraduate student sample was investigated. Height-fearful (n = 50) and non-fearful (n = 50) groups were formed on the basis of extreme scores to the heights item on the FSS-III (Wolpe & Lang, Behaviour Research and Therapy, 2, 27-30, 1964). Subjects were then assessed with a battery of measures including the Acrophobia Questionnaire (Cohen, Behaviour Therapy, 18, 17-23, 1977), self-rating of severity (Marks & Mathews, Behaviour Research and Therapy, 17, 263-267, 1979), global rating of severity (Michelson, Behaviour Research and Therapy, 24, 263-275, 1986), and a new comprehensive origins questionnaire constructed by the authors. Results obtained question the significance of simple associative-learning events in the acquisition of fear of heights. Only 18% of fearful Ss were classified as directly conditioned cases. Furthermore, no differences between groups were found in the proportion of Ss who knew other height-fearfuls, had experienced relevant associative-learning events, or the ages at which these events had occurred. Finally, no relationships between mode of acquisition and severity or individual response patterns were obtained. In general, the data were consistent with the non-associative, Darwinian accounts of fear acquisition that continue to attract theorists from a variety of backgrounds (e.g. Bowlby, Attachment and loss. London: Penguin, 1975; Clarke & Jackson, Hypnosis and behaviour therapy: The treatment of anxiety and phobias. New York: Springer, 1983; Marks, Fears, phobias and rituals: Panic anxiety and their disorders. New York, Oxford Univ. Press, 1987). Differences with previous studies in which classical conditioning has accounted for the majority of cases are discussed in terms of the methodological differences across studies. PMID- 8512538 TI - The hoarding of possessions. AB - Three studies of nonfood hoarding are reported. Findings support the reliability and validity of a Hoarding Scale. Furthermore, the findings indicate a number of features of hoarding behavior. Hoarding was associated with indecisiveness, perfectionism (especially maladaptive evaluative concern) and obsessive compulsive symptoms among college students and community volunteers. Hoarders tended to buy extra things in order not to be caught without a needed item, and they carried more 'just-in-case' items in purses, pockets and cars. Onset of hoarding was childhood and adolescence. Hoarders had more first degree relatives who engaged in excessive saving than nonhoarders, and hoarders were less likely to be married. There was no evidence to suggest that hoarding was related to material deprivation. A model was suggested which conceptualizes hoarding as an avoidance behavior tied to indecisiveness and perfectionism. Saving allows the hoarder to avoid the decision required to throw something away, and the worry which accompanies that decision (worry that a mistake has been made). Also, it allows hoarders to avoid emotional reactions which accompany parting with cherished possessions, and results in increased perception of control. PMID- 8512539 TI - Claustrophobic fear behavior: a test of the expectancy model of fear. AB - The present study examined Reiss and McNally's expectancy model in the prediction of claustrophobic fear, measured across three domains. Non-clinical subjects (N = 117) reporting claustrophobic concerns were administered a behavioral approach test to a claustrophobic chamber. Consistent with the expectancy model, danger expectancy, anxiety expectancy and the interaction of anxiety sensitivity and anxiety expectancy accounted for unique portions of behavioral performance, with other variables partialled out. The expectancy model variable set, however, did not meaningfully relate to subjective fear or heart-rate reactivity. The formulation of anxiety sensitivity as a measure of the salience of anxiety is discussed. These findings lend support to the theory as a model for the behavioral dimension of pathological fear, but not the subjective or physiological facets. PMID- 8512540 TI - Fearful and non-fearful panic attacks in a student population. AB - The phenomenon of non-fearful panic was investigated in a sample of 83 university students who reported histories of unexpected panic attacks. Based on severity ratings of individual panic symptoms, Ss were classified as having panic attacks characterized by No Fear (N = 22), Low Fear (N = 30) or High Fear (N = 31). The three groups were similar with respect to the age-of-onset of panic attacks, the frequency with which they experienced panic and the severity of panic symptoms unrelated to fear. However, Ss reporting fear during panic attacks were more likely to engage in avoidance behaviour and to use alcohol or drugs as ways of coping with panic. Only High Fear subjects showed significant elevations on self report measures of depression and global psychopathology. These results indicate that the experience of fear during panic attacks may be important in the transition from non-clinical panic to panic disorder, in a manner proportional to the amount of reported fear. PMID- 8512541 TI - Gender effects and alcohol use in panic disorder with agoraphobia. AB - Previous studies have found some significant, but weak, gender differences in panic and agoraphobia with females generally being more symptomatic. The present study sought to expand this line of research by examining alcohol use and self medication in relation to gender differences and measures of psychopathology. Seventy-four male and 162 female patients with panic disorder with agoraphobia were compared. There were some significant, but relatively small, gender differences with females reporting higher levels of phobic avoidance. Males reported significantly more weekly alcohol intake and also perceived alcohol to be a more effective strategy in coping with anxiety. Alcohol-related factors were significantly correlated with several measures of psychopathology for males but this was less evident in females. The correlations were not large but the results do suggest that a subset of males consume moderate to large amounts of alcohol, believe self-medication to be an effective anti-anxiety strategy, and yet report higher levels of psychopathology such as social fears. PMID- 8512542 TI - Cues for health-related imagery in analogue worriers: a brief report. AB - The role of specific cues for eliciting fearful imagery in a sample of analogue worriers was examined. Picture, script and audiotape disease-related cues were presented to 12 nonworriers and 13 analogue worriers who worried about health and disease. In general, the picture and audiotape cues were most anxiety provoking and elicited the most vivid imagery, respectively, although ratings were in the moderate range. Repeated trials of brief imagery had little effect on imagery ratings or estimates of risk for contracting the disease (i.e. worry statements) in the worry group. Disconfirmation of risk for contracting the diseases tended to lessen post-imagery anxiety but only after a series of imagery trials. On the other hand, disconfirming information lessened risk estimation overall. The findings are related to the conceptualization of worry and imagery proposed by Borkovec and Hu (Behaviour Research and Therapy, 28, 153-158 1990). PMID- 8512543 TI - Compulsivity and superstitiousness. AB - The relationship between superstitious beliefs and behaviors, and measures of obsessive-compulsive experiences was examined in this study. Both superstitious beliefs and superstitious behaviors were correlated with measures of compulsivity and obsessionality. Compulsive checking, but not compulsive cleaning (from the MOCI and the CAC-R) were correlated with superstitiousness. Both subscales from the Obsessional Thoughts Questionnaire were correlated with superstitiousness. The implications of these findings for the role of perceived control in obsessive compulsive phenomena were discussed. PMID- 8512544 TI - Dimensions of agoraphobia assessed by the Mobility Inventory. AB - Factor analyses of the When Accompanied and When Alone subscales of the Mobility Inventory (Chambless, Caputo, Jasin, Gracely & Williams, Behaviour Research and Therapy, 23, 35-44, 1985) were conducted using the responses of 177 panic disorder with agoraphobia patients. For both subscales a three-factor model was the most appropriate and accounted for approx. 60% of the variance in each case. The three factors were reliable and theoretically meaningful: fear of public places, enclosed spaces and open spaces. The fear of public places factor accounted for most of the explained variance and is discussed in relation to the social evaluation component of panic attacks. PMID- 8512545 TI - The Maternal Tolerance Scale and nocturnal enuresis. AB - The Maternal Tolerance Scale has consistently proved valuable in predicting those mothers who prematurely withdraw their children from treatment for nocturnal enuresis. This study sought to replicate the original work in examining the structure of the scale with an independent group of mothers. The results show the scale to have cross validity, although it appears weighted towards measuring intolerance rather than tolerance. A factor analysis produced 6 factors and these are discussed with regard to possible pathways leading to the development of intolerance. PMID- 8512546 TI - [Experimental reproduction of the respiratory form of infection with the agent of epidemic late abortion of swine]. AB - Porcine reproductive and respiratory syndrome has been observed in a large swine farm. Diagnostic investigations were undertaken. Piglets infected with homogenate from the lung of a sick gilt developed biphasic fever up to 42 degrees C, inappetence and apathy. A few piglets showed red-blue discolored parts of the ears and of the skin in the abdominal region. A cytopathogenic agent has been isolated on cultivated alveolar-macrophages. Infection of another group of piglets with macrophages-propagated agent resulted in similar clinical signs too. Organs of euthanatized piglets have been examined anatomical, histological and with the fluorescent antibody technique. Specific fluorescence could be seen in tonsils, bronchial lymph nodes, spleen and in pathological-changed parts of the lungs. Antibodies against PRRS-virus were detected in blood samples of experimentally infected pigs. PMID- 8512548 TI - Experimental studies on in vitro maturation of porcine oocytes. I. Effects of medium, energy source and protein source on in vitro maturation rate. AB - Effects of culture medium, energy and protein source on in vitro maturation of cumulus-intact porcine oocytes were examined. The bicarbonate buffered Whittens medium was superior to the PB1 medium buffered with phosphate salts in supporting in vitro maturation. However, modification of energy source of the PB1 medium by reducing Na-pyruvate concentration and adding lactate salts gave also high maturation rate. The supplementation of Whittens medium with 1 g and 3 g BSA/l as a protein source significantly increased incidence of maturation and improved handling of oocytes. There was no significant difference in the ability of low concentration (1 g/l) and high concentration (3 g/l) of BSA in culture medium to support maturation. PMID- 8512547 TI - [Development of an enzyme immunoassay for the detection of antibodies from hens and mice against Newcastle disease virus]. AB - The development of an enzyme-immuno-assay (EIA) for detection of avian and mouse antibodies against the Newcastle-Disease Virus is shown. The antigen preparation was the centre of the experiments. The basic assay programme and selected test steps were optimized. The established assay is part of the EIA-control system for a SPF (specific-pathogen-free)-flock and also the essential screening method for the production of anti-NDV-monoclonal antibodies. PMID- 8512549 TI - Experimental studies on in vitro maturation of porcine oocytes. II. Effects of estradiol-17 beta and progesterone. AB - The simple compounded semi-defined Whitten's medium was supplemented with estradiol-17 beta and progesterone to examine whether they influence the nuclear maturation of porcine cumulus-oocyte complexes. Addition of estradiol-17 beta at concentrations of 1.0 microgram/ml and 10.0 micrograms/ml significantly inhibited the nuclear maturation in comparison to the control group. No significant inhibition of estradiol-17 beta was observed at concentration of 0.1 microgram/ml with respect to the control. After addition of synchronous or subsequent (12 h after the incubation with estradiol-17 beta) supplementation of progesterone at concentration of 1 microgram/ml, maturation rates were as high as control. So progesterone overcame the inhibitory effect of estradiol-17 beta. PMID- 8512551 TI - [The occurrence of Prototheca in fecal samples of cattle]. AB - Prototheca spp. were detected in 146 (48.7%) of culturally examined fecal samples of cattle, using the selective medium, developed by Pore (1973). 114 fecal samples (78.1%) contained a monoculture of Prototheca (P.) zopfii, while 10 fecal samples (6.8%) contained a monoculture of P. moriformis. In further 22 fecal samples (15.1%) a mixed culture of P. zopfii and P. moriformis was detected. The results of this study permit to conclude that cattle can harbour and shed Prototheca spp. in variable frequency. PMID- 8512550 TI - [Veterinary radiology in Germany, Switzerland and Austria: a comparative analysis of problems]. AB - The result of an investigation in 1988/89 to grasp the problems of veterinary radiology in Austria left some uncertainties. By an enquiry of 200 vets (49% answered) additional information was received. A comparison between Austria, Germany and Switzerland revealed the same problems: neglected darkroom work. The causes are absent or not seldom false advice by medical/technical firms, the lacking willingness of vets to become advised, false parsimony and insufficient offer of meetings and seminars providing the physical know-how in producing X-ray pictures. PMID- 8512553 TI - Synthesis of beta-hematin by dehydrohalogenation of hemin. AB - beta-Hematin, the metalloporphyrin coordination polymer present in malaria pigment, is prepared in high yield by the abstraction of HCl from hemin with a non-coordinating base in strictly anhydrous conditions. The product of this preparation is characterized by elemental analysis, infrared and diffuse reflectance spectroscopies and demonstrated to be identical to prior preparations. PMID- 8512552 TI - Muscarinic receptors stimulate Ca2+ influx via phospholipase A2 pathway in ileal smooth muscles. AB - Receptor-mediated changes in intracellular Ca2+ in ileal longitudinal smooth muscles of guinea pig were studied. Stimulation of muscarinic receptors by carbachol induced both Ca(2+)-influx through plasma membranes and Ca(2+)-release from intracellular stores. Pretreatment of the muscle with an inhibitor of phospholipase A2 abolished the Ca2+ influx but not the Ca(2+)-release, whereas an inhibitor of phospholipase C showed opposite effects. The inhibitors of cyclooxygenase and lipoxygenase enhanced the muscarinic receptor-induced Ca(2+) influx. Addition of arachidonic acid mimic the receptor-induced Ca(2+)-influx. Treatment of muscles with pertussis toxin abolished the receptor-induced release of arachidonic acid as well as Ca(2+)-influx, but was less effective on the IP3 formation and the Ca(2+)-release. Taken together, our results suggest that phospholipase A2 but not phospholipase C pathway is involved in the muscarinic receptor-induced Ca(2+)-influx in ileal smooth muscle. PMID- 8512554 TI - Characterization of an anti-beta-galactosidase antibody recognizing a precursor but not a mature enzyme in solution. AB - A monospecific antibody was raised against a recombinant human 84-kDa beta galactosidase precursor protein, which had been produced with a baculovirus gene expression system and affinity-purified. It bound to the 64-kDa mature enzyme protein extracted from human fibroblasts and the antigenic recombinant precursor on immunoblotting, but neither the fibroblast-derived mature enzyme nor the 64 kDa mature protein-like tryptic product of the recombinant precursor protein was immunoprecipitated. We conclude that it specifically recognized the precursor but not the mature protein in solution. Immunoprecipitation with this anti-precursor antibody revealed that the precursor protein mainly accounted for the residual enzyme activity in fibroblasts from an adult GM1-gangliosidosis patient, and the mature protein accounted for the activity in fibroblasts from a juvenile GM1 gangliosidosis patient. PMID- 8512555 TI - Leu143 in the putative fourth membrane spanning domain is critical for amiloride inhibition of an epithelial Na+/H+ exchanger isoform (NHE-2). AB - A family of Na+/H+ exchanger isoforms (called NHE1, NHE2, and NHE3) which exhibits a wide range of amiloride sensitivity has recently been cloned and characterized. A part of the domain, which determines amiloride sensitivity in the epithelial Na+/H+ exchanger isoform, NHE2, was identified by site-directed mutagenesis and functional studies using cDNAs stably expressed in a fibroblast cell line. It has previously been reported that AR300, an amiloride resistant mutant of the ubiquitous Na+/H+ exchanger isoform, NHE1, is 30-fold more resistant to methylpropyl amiloride (MPA) compared to NHE1 and contains a single amino acid substitution of L167F in the fourth putative transmembrane helix, which corresponds to L143 in NHE2. Therefore, in the present study point mutational substitutions were introduced into the equivalent of this fourth transmembrane helix of rabbit NHE2 (including Y144F; L143F; L143F and Y144F) to mimic the corresponding amino acids in NHE1, NHE3 (another epithelial isoform) and AR300, respectively. NHE2/L143F (mimicking NHE3) increased the IC50 for amiloride by 5-fold and for ethylisopropyl amiloride (EIPA) by 20-fold. Similarly, NHE2/L143F and Y144F (mimicking AR300) increased the resistance to both amiloride and EIPA by 10-fold. On the other hand, NHE2/Y144F (mimicking NHE1) did not affect the sensitivity to amiloride or EIPA, and this mutant, like wild type NHE2, is partially resistant to EIPA. Thus, amino acid 143 of NHE2 is critical for, but is not the only amino acid responsible for, amiloride and EIPA inhibition of Na+/H+ exchange. That none of the mutations studied altered the Na+ affinity of these Na+/H+ exchangers further suggests that amiloride binding and Na+ transport sites are not identical. PMID- 8512556 TI - Improved enzyme immunoassay for human basic fibroblast growth factor using a new enhanced chemiluminescence system. AB - An enhanced chemiluminescence reaction has been incorporated into an enzyme immunoassay (EIA) for human basic fibroblast growth factor (hbFGF). We developed a new luminol derivative, designated L-012 and a new enhancer, 4-(4 hydroxyphenyl)thiazole. Using these compounds, the detection limit of hbFGF was improved to 0.1 pg/assay, which was 10-20 and 2 times better than the o phenylenediamine colorimetric and luminol chemiluminescence assays, respectively. The average concentration of bFGF in sera from 25 normal volunteers was 5.9 pg/ml. On the other hand, serum bFGF levels were elevated in renal, lung and brain tumor patients. The data presented here indicate that the serum bFGF level could be a useful diagnostic marker for these tumors. Furthermore, these new compounds could easily be applied to any other EIA that uses horse radish peroxidase to improve sensitivity. PMID- 8512557 TI - Partial structure of the gene encoding the 78 kDa gastrin binding protein excludes a close relationship with the peroxisomal trifunctional enzyme. AB - A 10.9 kb porcine genomic clone encoding nucleotides 124-732 of the cDNA for the porcine 78 kDa gastrin-binding protein has been isolated and characterized. The coding sequence is interrupted by 7 introns, which vary in length from 93 to 3000bp. The positions of the intron/exon junctions are different from the junctions in the gene encoding the rat peroxisomal trifunctional enzyme. Despite 33% amino acid sequence identity between the two proteins it is concluded that the porcine gastrin binding protein is not closely related to the rat trifunctional enzyme. PMID- 8512558 TI - Alpha 1-trypsin immunoreactivity in Alzheimer disease. AB - This study is the initial demonstration of trypsin-like immunoreactivity within the human CNS. Using two monoclonal antibodies to alpha 1-trypsin, we found trypsin-like immunoreactivity associated with the senile plaques of Alzheimer disease. Immunoblots prepared from homogenized Alzheimer and control cortex showed increased amounts of the 24,000Da alpha 1-trypsin species in diseased compared to control tissue. We suggest an alteration in alpha 1-trypsin protease regulation could be important in the formation of senile plaques and the pathogenesis of Alzheimer disease. PMID- 8512559 TI - Inhibition of CMP-N-acetylneuraminic acid:lactosylceramide sialyltransferase by nucleotides, nucleotide sugars and nucleotide dialdehydes. AB - The effects of nucleotides, nucleotide sugars and nucleotide dialdehydes on the activity and kinetics of cytidine 5'-monophospho-N-acetylneuraminic acid:lactosylceramide (alpha 2-->3) sialyltransferase (SAT-1) in microsomes derived from embryonic chick brain were investigated. Although under physiological conditions this enzyme utilizes a CMP-sugar as substrate, it was found that UDP-dialdehyde was an effective inhibitor of SAT-1 activity. CMP dialdehyde was only slightly more efficient at inhibiting SAT-1 activity. Similar findings were found for the inhibitory effects of UDP versus CMP. In addition, two UDP-sugars (UDP-Gal and UDP-GalNAc) were also slightly inhibitory. Kinetic analyses demonstrate that both UDP- and CMP-dialdehydes are competitive inhibitors of SAT-1 activity. The data suggests that the substrate specificity of microsomal SAT-1 resides more in the sugar moiety, rather than in the nucleotide portion of the substrate. PMID- 8512560 TI - Formation of compact globular particles in interphase nuclei from rat liver under the effect of polyanions. AB - Treatment of the isolated nuclei with polyanions (PA) (heparin and dextran sulfate) at the PA/DNA ratio of about 1 in the 0.15-0.5 M ammonium acetate solution leads to rearrangement of the chromatin structure and formation of compact globular particles (GP) 40-70 nm in diameter, bound by fibrils of variable thickness (2-10 nm). GP formation is accompanied by a loss of nucleosomal periodicity in DNA organization. However, no considerable loss of the DNA contents has been found. At the PA/DNA ratio of more than 2, destruction of the DNP-network and aggregation of GP in larger globular structures are observed. The same effect is observed under the nuclease treatment. Under this condition nuclei lose a considerable part of DNA, but retain histones supposedly as histone PA aggregates. Therefore the joint effect of PA and salt on nuclei at certain conditions may lead to formation of artefact structures. PMID- 8512561 TI - Human liver calreticulin: characterization and Zn(2+)-dependent interaction with phenyl-sepharose. AB - A 60-kDa human calreticulin was isolated from liver homogenates. The protein was identified as calreticulin by its NH2-terminal amino acid sequence, by its mobility in SDS-PAGE, by its immunoreactivity with anti-calreticulin antibodies, by its Ca2+ binding, and by its localization to isolated ER membranes. In this study we show that Ca2+ binding to calreticulin results in Ca(2+)-dependent aggregation and precipitation of the protein. We also show that calreticulin and calsequestrin bind Zn2+ in 65Zn2+ overlay. In addition we have discovered that calreticulin exhibits a Zn(2+)-dependent interaction with hydrophobic matrix of phenyl-Sepharose that can be utilized in the purification of the protein. PMID- 8512562 TI - Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. AB - The presence of the secreted angiogenic molecule, vascular permeability factor/vascular endothelial growth factor, was investigated in human retinal pigment epithelial cells. Northern and in situ hybridization analysis of cultured cells identified vascular permeability factor/vascular endothelial growth factor mRNA. Western analysis of cell lysates identified a 42 kD protein that comigrated with human recombinant vascular permeability factor/vascular endothelial growth factor. Immunoassay measurements detected vascular permeability factor/vascular endothelial growth factor protein in cell lysates and conditioned media in vitro and in cell lysates isolated directly from post-mortem eyes. These data demonstrate that human retinal pigment epithelial cells can synthesize the secreted angiogenic peptide vascular permeability factor/vascular endothelial growth factor in vitro and in situ. The production and secretion of this factor by human retinal pigment epithelial cells may be important in the pathogenesis of ocular neovascularization. PMID- 8512563 TI - Brain protein kinase PK40erk converts TAU into a PHF-like form as found in Alzheimer's disease. AB - The novel protein kinase PK40 (1) was characterized by its ability to phosphorylate Lys-Ser-Pro sites in neurofilament and TAU proteins. PK40 is now recognized to be a member of the family of External-stimulus Regulated Kinases (ERKs) by its reactivity with ERK-specific antibodies and will therefore be called PK40erk. Bovine TAU or recombinant human TAU proteins can be hyperphosphorylated by PK40erk to produce the electrophoretic mobility shifts and certain immunochemical properties characteristic of PHF-TAU isolated from Alzheimer's disease brain tissue. PK40erk may play a crucial role in the etiology of this disease. PMID- 8512564 TI - Molecular cloning and sequencing of a human somatostatin receptor, hSSTR4. AB - We recently reported the cloning of a somatostatin receptor (SSTR) subtype from a rat genomic library designated rSSTR4. In the present study, we report the cloning of the human SSTR4 gene. A human genomic library was screened with a 1.2 kb fragment of rSSTR4 containing the full open reading frame and a genomic clone, hSSTR4, was isolated. The deduced amino acid sequence of this clone encoded a protein of 388 amino acids and is a member of the G-protein coupled receptor superfamily. Comparison of rat and human SSTR4 sequences demonstrated 89% identity. In addition, the sequence of hSSTR4 shows 61%, 46%, and 47% sequence identity with previously identified isoforms hSSTR1, hSSTR2, and hSSTR3, respectively. PMID- 8512565 TI - A vaccinia virus vector for efficiently introducing into hippocampal slices. AB - We have developed a novel technique using vaccinia virus for highly efficient introduction of foreign genes into viable cells of brain slice to study function of nervous system. Hippocampal slices of adult guinea pigs were infected with a vaccinia virus carrying a gene for beta-galactosidase (beta-gal) as a reporter gene. Expression of beta-galactosidase was first detected after 5 hours and reached maximum after 16 to 24 hours. Light microscopic observation revealed that beta-galactosidase was expressed uniformly in the CA1-CA3 pyramidal cell layer, granule cell layer of dentate gyrus and glial cells. Serial sections of infected slices showed that cells were uniformly infected throughout the thickness of the slice. Thus, the vaccinia virus system provides a convenient gene transfer tool for studying brain function in cultured slice system. PMID- 8512566 TI - Active conformation of the pyrokinin/PBAN neuropeptide family for pheromone biosynthesis in the silkworm. AB - Members of the pyrokinin/pheromone biosynthesis activating neuropeptide family elicit pheromonotropic activity in at least two species of moths. We report that in the silkworm (Bombyx mori) the conformationally constrained octapeptide analog cyclo[Asn-Thr-Ser-Phe-Thr-Pro-Arg-Leu] retains 10% of the pheromonotropic activity of naturally occurring Bom-PBAN-I, a 33 amino acid peptide. Previous data from CD, NMR, and molecular dynamics analyses indicate a type I beta-turn conformation for active core residues Thr-Pro-Arg-Leu in the cyclic analog. The rigidity of the well-defined backbone structure of this cyclic pyrokinin/PBAN analog suggests that it represents the conformation necessary to interact with the pheromonotropic receptor site in the silkworm. PMID- 8512567 TI - Solution structure of trypsin modulating oostatic factor is a left-handed helix. AB - The solution structure of trypsin modulating oostatic factor (TMOF), a decapeptide (H-YDPAPPPPPP-OH) hormone that signals the termination of trypsin like biosynthesis in mosquito midgut epithelial cells, was determined by 2-D 1H nuclear magnetic resonance spectroscopy and molecular modeling. The peptide forms a rod-shaped left-handed helix about 30 A long. No evidence was found to support a poly-L-proline beta-turn model. Hydrophobic contacts between the rings of tyrosine 1 and proline 3 may enhance the stability of the N-terminal segment. This peptide provides an interesting exception to the normal chemical shift index (csi) rules. Our results suggest that a sequence of positive csi indices, normally expected for a beta-strand structure, could also describe a left-handed poly-L-proline-like helix. PMID- 8512568 TI - Thymosin beta-4 expression is correlated with metastatic capacity of colorectal carcinomas. AB - We constructed a "non-metastatic cell (SW837)--metastatic cell (PMCO1)" subtraction library and identified one cDNA that was strongly expressed in SW837 but weakly expressed in PMCO1. The nucleotide sequence of the cDNA revealed that it encoded thymosin beta-4. Four non-metastatic cell lines, which produced no experimental liver metastasis in nude mice, showed high expression of thymosin beta-4. However three of four metastatic cell lines showed weak expression of thymosin beta-4. Among surgical materials, thymosin beta-4 expression was high in tumors without metastasis in comparison with non-tumorous mucosa, but one case with liver metastasis showed decreased expression in both the primary and metastatic tumors. We suspect that down-regulation of thymosin beta-4 expression is correlated with the metastatic capacity of colorectal carcinomas. PMID- 8512569 TI - Cloning and sequencing of goldfish activin subunit genes: strong structural conservation during vertebrate evolution. AB - Inhibin and activin are structurally related dimeric peptides sharing two distinct but related subunits, beta A and beta B. By using polymerase chain reaction (PCR), we have cloned and sequenced activin beta A and beta B genes encoding the mature region of the peptides from the goldfish genomic DNA. A single form of beta A and two forms of beta B subunits were found. There is high identity with mammalian counterparts; the goldfish beta A subunit has 78% protein sequence identity with human beta A subunit, and the two beta B subunits have more than 94% sequence identity with human beta B subunit. This is the first demonstration of the activin family of peptides in the fishes. PMID- 8512570 TI - Interaction of Trypanosoma cruzi with cells with altered glycosylation patterns. AB - Glycosylation mutants of chinese hamster ovary cells were used to analyse the role played by surface-exposed carbohydrates on the process of interaction of Trypanosoma cruzi with the host cell. Adhesion and invasion of the parasites were markedly reduced in cells which express very few sialic acid residues. Infection levels similar to those obtained with the parental cell could be obtained after sialylation of the mutant cell using exogenous fetuin as sialic acid donor and T. cruzi trans-sialidase. The results obtained show that host cell sialic acid residues are involved in the process of attachment to and penetration of T. cruzi into the host cell. PMID- 8512571 TI - Continuous monitoring of nitric oxide release from human umbilical vein endothelial cells. AB - Direct measurement of nitric oxide (NO) release is pivotal for understanding its role in the regulation of vascular tone. However, data on the direct measurement of NO have been scarce. Recent description of NO-selective electrode has prompted us to examine NO release from endothelial cells using this approach. In the present study, we continuously monitored [NO] in the incubation medium conditioned by cultured human umbilical vein endothelial cells (HUVEC) with an amperometric NO-sensor. The HUVEC released NO on stimulation with several agonists such as alpha-thrombin, bradykinin, L-arginine and ionomycin; the responses were characterized by an initial rise and a subsequent sustained increase. Activation of Ca/calmodulin system resulted in a robust elevation in [NO], occasionally displaying an oscillatory component. Calmidazolium pretreatment attenuated the ionomycin-induced response. Pretreatment with phorbol ester suppressed the ionomycin-induced NO release from HUVEC. Forskolin pretreatment did not modify NO release elicited by ionomycin. These findings indicate that the synthesis/release of NO in endothelial cells is a Ca/calmodulin dependent step. Activation of protein kinase C interferes with the Ca/calmodulin induced activation of NOS in endothelial cells. Thus, the present study shows that NO synthase is a substrate for phosphorylation by different kinases which modulate the activity of the enzyme as determined by continuous monitoring of NO release from endothelial cells using a specific NO-sensor. PMID- 8512572 TI - Autoinduction of platelet derived growth factor (PDGF) A-chain mRNA expression in a human malignant melanoma cell line and growth inhibitory effects of PDGF-A chain mRNA-specific antisense molecules. AB - Autoinduction of PDGF-A-chain mRNA's was demonstrated in cells of a human malignant melanoma cell line (HTZ 19), indicating a PDGF-induced amplification of an autocrine growth factor loop mechanism. PDGF-alpha receptors were detected by immunocytochemistry in HTZ 19 melanoma cells. Exogenously administered PDGF-AA exerted an increase in cell proliferation by 70% at 200 ng/ml PDGF in serum supplemented cell culture medium. Antisense phosphorothioate oligodeoxynucleotides (S-ODN's), specifically targeted against PDGF-A-chain mRNA, reduced cell proliferation of HTZ 19 melanoma cells by 62% at a concentration of 5.0 microM, also only in serum-enriched medium. These findings strongly suggest that PDGF-AA homodimers may be an autocrine growth factor for HTZ 19 melanoma cells but require synergistic interaction with serum components. PMID- 8512573 TI - Sphingosine is endogenous to cardiac and skeletal muscle. AB - Endogenous sphingosine levels have been determined for rabbit skeletal and cardiac muscle. The sphingosine content of whole muscle tissue was compared to cytosol fractions and to particulate fractions enriched in transverse tubules or sarcoplasmic reticulum membranes. Cardiac and skeletal muscle tissue exhibited high levels of sphingosine (17 pmol/g). Muscle cytosol fractions contained potentially significant levels of sphingosine when expressed as a concentration (0.6-1.3 microM). Isolated T-tubule membranes displayed high sphingosine contents (1400 pmol/mg), making the T-tubules a major source of sphingosine in the muscle cell. The presence of sphingosine in muscle cells suggests that sphingosine may be a physiologically important second messenger in cardiac and striated muscle. PMID- 8512574 TI - Effect of staurosporine on suppression of heat shock gene expression and thermotolerance development in HT-29 cells. AB - Staurosporine, an inhibitor of protein kinase C (PKC), was selected to determine the effect of drug on the development of thermotolerance and the expression of heat shock protein genes. Experiments were carried out with human colon carcinoma HT-29 cells. Heat shock induction consisted of 45 degrees C for 15 min and subsequent incubation at 37 degrees C for 6 h. Thermotolerance developed rapidly, reached its maximum at 6 h after heat shock, and decayed gradually. At maximal thermal resistance, thermotolerance ratio at 10% isosurvival was 3.8. The development of thermotolerance was markedly inhibited by treatment with staurosporine (0.1-5.0 micrograms/ml). Exposure to 1.0 and 5.0 micrograms/ml staurosporine reduced thermotolerance ratio to 1.8 and 1.1 respectively. Further, the levels of heat shock protein genes (HSP 28 and 70) encoding mRNA were equally reduced by the drug treatment. These results suggest that PKC is involved in the regulation of heat shock gene expression and development of thermotolerance. PMID- 8512575 TI - Inhibition of UV-damaged DNA recognition activity in HeLa cells by calcium ionophore A23187: potential involvement of cytosolic proteins. AB - A UV-damage recognition protein (UVDRP) was detected from HeLa nuclear extracts using an in vitro DNA-binding assay. Treatment of cells with a Ca2+ ionophore (A23187) caused a dramatic inhibition of the UVDRP binding activity from nuclear extracts. In the absence of EDTA, addition of cytosolic extracts to the binding reaction effectively blocked the UVDRP binding activity, associated with an increased nuclease activity. However, pretreatment of cytosolic extracts with proteinase destroyed a majority of the inhibitory effect on UVDRP binding activity. Using extracts from A23187-treated cells, a similar conclusion was drawn except that the inhibitory effect of cytosolic extracts on UVDRP binding was completely diminished by proteinase K. In addition, inclusion of the cytosolic extracts in the binding reaction did not alter the UVDRP binding dissociation pattern by specific competitors. These results suggest the potential involvement of cytosolic proteins, probably through a "all-or-none" action mechanism, in the recognition of UV-damaged DNA of HeLa cells. PMID- 8512576 TI - A comparative analysis of cDNA-derived sequences for rat and mouse beta 3 integrins (GPIIIA) with their human counterpart. AB - Alpha IIb beta 3 (GPIIb-IIIa), the platelet receptor for fibrinogen, is a member of the integrin superfamily. We have now cloned the mouse and rat beta 3 cDNAs. These data represent the first available non-human beta 3 sequences, allowing important comparative analyses. Both beta 3 sequences are highly homologous with human beta 3, well above average rodent-human protein homology of 79%. The ligand binding domains (aa) 109-171 and 204-229) are, respectively, 90% and 100% homologous. The beta 3 transmembrane and the cytoplasmic tail are surprisingly highly conserved, being 97% and 100% homologous, respectively, but share little homology with beta 1, or beta 2. This latter difference argues strongly in favor for a crucial beta 3-specific function for these domains. In conclusion, we present the first comparative analysis of beta 3 chains and demonstrate high overall homology. The biological implications of these comparisons are discussed. PMID- 8512577 TI - Cloning and expression of a novel human DNA binding protein, PO-GA. AB - We have cloned a novel human DNA-binding protein from a HeLa cDNA expression library using the cognate DNA binding site of a transcription factor, PO-B. Further hybridization screening with the initial clone produced contiguous cDNA sequence of 4508 bp and a complete open reading frame encoding a 128 kDa protein, PO-GA. Northern analysis revealed a wide distribution of PO-GA mRNA in most human tissue. However, PO-GA mRNA levels were lower in lung and kidney and undetectable in placental tissue. A DNA-binding fragment of PO-GA expressed in E. Coli bound selectively to the PO-B element and other GA-rich double-stranded DNA sequences and to certain single-stranded DNA sequences. PO-GA has regions of homology to E. coli and yeast DNA ligases, and to proteins involved in DNA repair. Thus, in addition to a potential role in transcription, PO-GA may also be involved in DNA repair or replication. PMID- 8512578 TI - High glucose causes delayed fetal lung maturation as measured by fluorescence anisotropy. AB - Fluorescence anisotropy has been used to estimate the microviscosity of the surfactant phospholipid bilayer and no predict fetal lung maturity in human amniotic fluid; its usefulness in in vitro systems has been recently demonstrated. To investigate the effect of high glucose on lung development, anisotropy measurements were performed on 20-day fetal rat lung explant homogenates and culture media after culture for 48 hours in medium containing final concentrations of 10, 50, and 100mM glucose. Anisotropy of lung tissue cultured in 100mM glucose was significantly increased when compared to those cultured in 10mM glucose (p < .01). After 48 hours, the media from samples grown in 100mM glucose had significantly higher anisotropy (.2210 +/- .0031) than did media from explants grown in 50mM glucose (.2027 +/- .0079; p < .05), or in 10mM glucose (.1886 +/- .0046; p < .001). Relative fluorescence intensity of explants grown in 100mM glucose was 74.4 +/- 5.7% of those grown in 10mM glucose (p < .01). Fluorescence intensity of media was also decreased by 15-30% under higher glucose considerations (p < .05). These data suggest that surfactant synthesized and secreted under high glucose conditions, such as exist in the infant of the diabetic gestation, may have qualitative as well as quantitative changes. PMID- 8512579 TI - Mechanisms for regulating tone in lymphatic vessels. PMID- 8512580 TI - Reoxygenation following hypoxia stimulates lipid peroxidation and phosphatidylinositol breakdown in kidney cortical slices. AB - Reoxygenation of hypoxic (120 min at 37 degrees) rabbit kidney cortical slices in vitro resulted in a rapid increase in lipid peroxidation and phosphatidylinositol hydrolysis. No changes in phosphatidylinositol breakdown occurred during hypoxia or upon reoxygenation in the absence of calcium. Incubation of renal slices with carbon tetrachloride resulted in increased lipid peroxidation but had no effect on phosphatidylinositol breakdown. It is concluded that altered intracellular calcium homeostasis during reoxygenation is involved in mediating increased phosphatidylinositol hydrolysis through activation of a specific phospholipase C, but that oxidative stress per se does not have a significant effect on the inositol phosphate secondary messenger response in this model system. PMID- 8512581 TI - Cytotoxic effects of biphenyl and hydroxybiphenyls on isolated rat hepatocytes. AB - The cytotoxic effects of biphenyl (BP) and its hydroxylated derivatives, o phenylphenol (OPP), m-phenylphenol (MPP), p-phenylphenol (PPP), 2-biphenylyl glycidyl ether (OPP-epoxide), phenyl-hydroquinone (PHQ), o,o'-biphenol (o,o' BPol) and p,p'-biphenol (p,p'-BPol), were investigated in freshly isolated rat hepatocytes. OPP, MPP and PPP, at concentration of 0.75 mM, resulted in the loss of intracellular ATP, glutathione (GSH) and protein thiols, causing cell death. OPP-epoxide and BP were less toxic than the OPP isomers. MPP or PPP compared with OPP caused serious impairments in oxidative phosphorylation in mitochondria isolated from rat liver. PHQ (0.75 mM) caused a rapid loss of intracellular ATP which preceded the onset of cell death. PHQ was more toxic than o,o'-BPol or p,p' BPol. PHQ dissolved in Krebs-Henseleit buffer without hepatocytes was rapidly converted to its corresponding quinone, phenyl-benzoquinone. The cytotoxicity produced by PHQ depends on the rate of formation of reactive intermediates. These results indicate that the addition of a hydroxyl group to the aromatic ring of BP enhances BP-induced cytotoxicity and that the mitochondria are a common target of the OPP isomers and other BP derivatives. In addition, the para- or meta-hydroxyl groups rather than the ortho-hydroxyl group increase the toxicity. The cytotoxicity produced by PHQ depends on the rate of formation of reactive intermediate(s) such as phenyl-benzoquinone. PMID- 8512582 TI - Inhibition of catechol-O-methyltransferase by 1-vinyl derivatives of nitrocatechols and nitroguaiacols. Kinetics of the irreversible inhibition by 3 (3-hydroxy-4-methoxy-5-nitro benzylidene)-2,4-pentanedione. AB - It is well known that activated alkene derivatives react with thiol groups according to a Michael's addition reaction. On the basis of the presence of at least one thiol group essential for the activity of catechol-O-methyltransferase (COMT), several 1-vinyl derivatives of nitrocatechol and nitroguaiacol were synthesized and tested as potential irreversible active site-directed inhibitors of COMT. All the synthesized products were potent inhibitors of partially purified pig liver COMT. However, the inhibition was reversible in most cases, with the exception of 3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione (compound 2) which inhibited COMT in an irreversible manner. When the inhibition of COMT was measured as a function of the length of time of pre-incubation with 2, biphasic kinetics were observed, suggesting the modification of at least two thiol groups which are essential for COMT activity. The analysis of the two parts of the inhibition curve as a function of the inhibitor concentration showed that compound 2 modified the more reactive group in a non-specific manner, while it behaved as an active site-directed inhibitor on the second slow-reacting thiol group. Importantly, a saturating concentration of S-adenosyl-L-methionine (AdoMet) in the pre-incubation mixture gave pseudo-first order kinetics, suggesting total protection of one thiol group. Magnesium ions had no effect on the protection of COMT by AdoMet. In the presence of 3,5-dinitrocatechol (DNC) slight protection of COMT was observed; when the inactivation of both groups was analysed independently, protection of the specifically modified group was detected, while the reaction with the other group was faster in the presence of DNC. When both AdoMet and DNC were present, inactivation of COMT by 2 was not observed, suggesting that both reacting groups are located at or near the active site. PMID- 8512583 TI - Dehydrogenase-dependent metabolism of alcohols in gastric mucosa of deer mice lacking hepatic alcohol dehydrogenase. AB - Deer mice (Peromyscus maniculatus) lacking hepatic alcohol dehydrogenase (ADH) have been used as a model for studies of ethanol elimination catalysed by non-ADH systems like catalase and cytochrome P450. However, in an in vivo study on these animals (ADH- deer mice), we detected reversibility in the oxidation of [2H]ethanol, indicating that a major part of the ethanol elimination was due to a dehydrogenase (Norsten et al., J Biol Chem 264: 5593-5597, 1989). In the present investigation, we found significant ethanol oxidizing activity in the gastric mucosa of the deer mice. Reversibility was demonstrated by the use of [2H]acetaldehyde and gas chromatography-mass spectrometry of the products. The kinetic 2H isotope effect of the gastric system was about 3.0 and the system was comparatively insensitive to inhibition by 4-methylpyrazole. The behavior of the deer mice gastric ADH in isoelectric focusing and its higher activity with longer alcohols as substrates indicated similarity with the previously described human class IV enzymes. Our data are in agreement with results obtained in vivo and indicate that ethanol is oxidized extrahepatically in ADH- deer mice. This has to be taken into account when deer mice are used to study non-ADH-dependent ethanol oxidation in vivo. PMID- 8512584 TI - Effect of oxidant exposure on thiol status in the intestinal mucosa. AB - The intestinal epithelium is likely to be exposed to oxidants derived from diet, bacterial metabolic products or endogenously formed cellular metabolites. Glutathione, being the major intracellular thiol, provides protection against oxidative injury. The present study looks at the effect of luminal exposure to oxidants on intestinal thiol status. Different oxidants were placed in the lumen of anesthetized rats for 30 min and the mucosal non-protein and protein-bound thiols were quantitated using HPLC. Oxidant exposure altered the thiol redox status and increased the oxidized glutathione (GSSG) level 6-7-fold and protein bound reduced glutathione (GSH) 2-fold, whereas the non-protein GSH level remained the same or increased slightly. This could be due to either increased mucosal GSH synthesis or transport from circulation. After incubation with buthionine sulfoximine, a specific inhibitor of GSH synthesis, prior to oxidant exposure, the same increase in GSSG and GSH in the mucosa was seen. Oxidant exposure also decreased the plasma GSH level by 50%. The other cellular non protein thiols, cysteine and cystine, did not change after luminal exposure to oxidants. These results suggest that oxidant exposure stimulates uptake of GSH from the circulation to maintain mucosal GSH. PMID- 8512585 TI - Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria. AB - Studies were undertaken to investigate the principal actions underlying mercury induced oxidative stress in the kidney. Mitochondria from kidneys of rats treated with HgCl2 (1.5 mg/kg i.p.) demonstrated a 2-fold increase in hydrogen peroxide (H2O2) formation for up to 6 hr following Hg(II) treatment using succinate as the electron transport chain substrate. No increase in H2O2 formation was observed when NAD-linked substrates (malate/glutamate) were used, suggesting that Hg(II) affects H2O2 formation principally at the ubiquinone-cytochrome b region of the mitochondrial respiratory chain in vivo. Together with increased H2O2 formation, mitochondrial glutathione (GSH) content was depleted by more than 50% following Hg(II) treatment, whereas formation of thiobarbiturate reactive substances (TBARS), indicative of mitochondrial lipid peroxidation, was increased by 68%. Studies in vivo revealed a significant concentration-related depolarization of the inner mitochondrial membrane following the addition of Hg(II) to mitochondria isolated from kidneys of untreated rats. This effect was accompanied by significantly increased H2O2 formation, GSH depletion and TBARS formation linked to both NADH dehydrogenase (rotenone-inhibited) and ubiquinone-cytochrome b (antimycin-inhibited) regions of the electron transport chain. Oxidation of pyridine nucleotides (NAD[P]H) was also observed in mitochondria incubated with Hg(II) in vitro. In further studies in vitro, the potential role of Ca2+ in Hg(II)-induced mitochondrial oxidative stress was investigated. Ca2+ alone (30 400 nmol/mg protein) produced no increase in H2O2 and only a slight increase in TBARS formation when incubated with kidney mitochondria isolated from untreated rats. However, Ca2+ significantly increased H2O2 and TBARS formation elicited by Hg(II) at the ubiquinone-cytochrome b region of the mitochondrial electron transport chain, whereas TBARS formation was decreased significantly when the Ca2+ uptake inhibitors, ruthenium red or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA), were included with Hg(II) in the reaction mixtures. These findings support the view that Hg(II) causes depolarization of the mitochondrial inner membrane with consequent increased H2O2 formation. These events, coupled with Hg(II)-mediated GSH depletion and pyridine nucleotide oxidation, create an oxidant stress condition characterized by increased susceptibility of mitochondrial membranes to iron dependent lipid peroxidation (TBARS formation). Since increased H2O2 formation, GSH depletion and lipid peroxidation were also observed in vivo following Hg(II) treatment, these events may underlie oxidative tissue damage caused by mercury compounds. Moreover, Hg(II)-induced alterations in mitochondrial Ca2+ homeostasis may exacerbate Hg(II)-induced oxidative stress in kidney cells. PMID- 8512586 TI - Immune stimulation by an antisense oligomer complementary to the rev gene of HIV 1. AB - Mice developed massive splenomegaly and polyclonal hypergammaglobulinemia within 2 days after intravenous injection of a phosphorothioate oligomer that is antisense to a portion of the rev region of the HIV-1 genome. Histologic examination of spleens from injected animals showed marked expansion of a uniform appearing population of small lymphocytes and many mitoses. Spleen mononuclear cells (SMNCs) from injected animals showed approximately a 10-fold-increased uptake of [3H]thymidine and production of IgM and IgG. Flow cytometry analysis indicated that the responding cells were predominantly B-lymphocytes. The anti rev oligomer also was mitogenic in vitro and stimulated immunoglobulin production by normal mouse SMNCs and human peripheral blood mononuclear cells. Similar immunologic effects were observed with an anti-rev 21-mer phosphorothioate, truncated at the 3' end, but not with a 20-mer human p53 antisense phosphorothioate or a 28-mer anti-rev phosphodiester. These observations are consistent with the possibility that DNA sequences homologous to the rev gene participate in the regulation of mammalian lymphocyte activation, proliferation and maturation. PMID- 8512587 TI - Activation of the jun-D gene during treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine. AB - The jun-D gene is a member of the c-jun family of early response genes that code for DNA binding proteins. The present studies demonstrate that 1-beta-D arabinofuranosylcytosine (ara-C) increases jun-D expression in HL-525 myeloid leukemia cells. This induction by ara-C was maximal at 6 hr and transient. In contrast, ara-C had no detectable effect on the gene coding for the cAMP responsive element binding protein 1. Nuclear run-on assays demonstrated that ara C treatment is associated with an increased rate of jun-D transcription. The results also show that jun-D transcripts are stabilized at a posttranscriptional level in ara-C-treated cells. Taken together, these results demonstrate that ara C induces expression of the jun-D gene and that this effect is regulated by transcriptional and posttranscriptional mechanisms. PMID- 8512588 TI - A mathematical model of the kinetics and tissue distribution of 2-fluoro-beta alanine, the major catabolite of 5-fluorouracil. AB - 2-Fluoro-beta-alanine (FBAL) is the major metabolite of 5-fluorouracil (FUra), one of the most widely used anticancer drugs. It has been suggested previously that FBAL and/or its metabolites may have a role in the hepatotoxicity, neurotoxicity and cardiotoxicity resulting from FUra chemotherapy. Studies in patients and experimental animals have demonstrated that FBAL has a prolonged elimination compared with the parent drug, FUra. In the present manuscript, a mathematical model is developed for the kinetics and tissue distribution of FBAL. This model is based on recently published data from a study of the pharmacokinetics and disposition of FBAL in rats (Zhang et al., Drug Metab Dispos 20: 113-119, 1992). Satisfactory agreement was achieved between predicted and measured values, permitting an accurate evaluation of the kinetic and distribution parameters for FBAL. This model indicates that: (1) FBAL accumulates in several tissues including brain, heart, spleen, and enterohepatic system; and (2) enterohepatic circulation of FBAL and its bile acid conjugates has an important role in FBAL kinetics and distribution as demonstrated by a model in which enterohepatic circulation parameters were deleted. PMID- 8512589 TI - Modulation of cisplatin cytotoxicity by permeabilization of the plasma membrane by digitonin in vitro. AB - Killing of human ovarian carcinoma 2008 cells by cisplatin (DDP) is in direct proportion to the amount of drug entering the cell. DDP and its analogue [3H]dichloro(ethylenediamine)platinum[II] ([3H]-DEP) enter cells relatively slowly. We found that the uptake of [3H]DEP into 2008 cells could be increased by treating the cells briefly with the plasma membrane-selective detergent digitonin. A similar effect was observed in an 11-fold DDP-resistant subline of 2008 cells, designated 2008/C13*5.25. A measurable effect was produced by concentrations as low as 5 microM, and 40 microM digitonin increased [3H]DEP accumulation at 1 hr by 4.4 +/- 0.2- and 6.5 +/- 0.7-fold (means +/- SD) in 2008 and 2008/C13*5.25 cells, respectively. The effect was rapid, occurring within 1 min. Increased [3H]DEP uptake was accompanied by increased platination of DNA (8.5-fold in 2008 cells and 18.5-fold in 2008/C13*5.25 cells), and by enhanced killing of both the DDP-sensitive and -resistant cells that was shown to be synergistic by median effect analysis. The combination index at 50% cell kill was 0.64 +/- 0.14 (values < 1 indicate synergy). We conclude that a brief exposure to digitonin can increase [3H]DEP uptake in vitro, and can overcome the impaired [3H]DEP accumulation associated with acquired DDP resistance. DDP and digitonin interact synergistically to increase tumor cell kill in vitro. PMID- 8512590 TI - Alteration of rat liver endoplasmic reticulum Ca(2+)-ATPase thiol integrity by ciprofibrate, a peroxisome proliferator. AB - Ciprofibrate (CP), a peroxisome proliferator, has been shown to reduce rat liver endoplasmic reticulum (ER) Ca(2+)-ATPase activity both in vitro and in vivo. The ER Ca(2+)-ATPase is highly susceptible to thiol reactivity, and maintenance of maximal enzyme activity is critically dependent upon the integrity of these thiol groups. We therefore investigated whether CP alters ER Ca(2+)-ATPase thiol groups as a possible mechanism of enzyme inhibition. Using a thiol immunoblot technique, free thiol groups specifically on the ER Ca(2+)-ATPase were localized. Exposure of freshly isolated rat liver microsomes to CP (500 microM) resulted in a loss of sulfhydryl reactivity on the ER Ca(2+)-ATPase protein at 107 kDa, as identified using the thiol immunoblot assay. However, when rat liver microsomes were exposed to CP in the presence of reduced glutathione (GSH), thiol groups on the ER Ca(2+) ATPase were protected. Also, the reduction of ER Ca(2+)-ATPase activity by CP could be ameliorated by co-incubation of rat liver microsomes with GSH. These observations indicate that CP reduces rat liver ER Ca(2+)-ATPase activity through interactions with free thiol groups located on this enzyme. PMID- 8512591 TI - Synergistic antiproliferative effects of interleukin-1 alpha and doxorubicin against the human ovarian carcinoma cell line (NIH:OVCAR-3). AB - Interleukin-1 alpha (IL-1 alpha) exerts antiproliferative effects on a human ovarian carcinoma cell line, NIH:OVCAR-3, which is resistant to clinically relevant concentrations of doxorubicin (DOX) and other chemotherapeutic agents. This action of IL-1 alpha depends on the presence of type I (80 kDa) receptors, although no quantitative relationship has been established between receptor occupancy and inhibition of cell growth. When NIH:OVCAR-3 cells were exposed to IL-1 alpha and DOX in combination, a mutual potentiation of the antiproliferative effects of the two agents was observed. This synergistic effect was not due to IL 1 receptor expression up-regulation by DOX, and receptor-dependent internalization of the cytokine was also unaffected. The involvement of IL-1 receptors is supported by the observation that synergism between the two agents was diminished (but not abolished) in the presence of a specific IL-1 receptor antagonist at concentrations blocking more than 75% of IL-1 alpha binding. DOX was found to significantly increase IL-1 alpha accumulation by NIH:OVCAR-3 cells after long-term (48 hr) exposure to the cytokine at 37 degrees, which might be due to increased nonspecific fluid phase uptake or to interference with cytokine degradation and/or release processes. The potent synergy of IL-1 alpha and DOX against ovarian carcinoma cells in vitro suggests that this drug combination may be effective against this disease in the clinic. PMID- 8512592 TI - Effects of peptidase inhibitors on binding at angiotensin receptor subtypes in the rat brain. AB - Sulfhydryl reducing agents affect angiotensin II (AII) receptor binding differentially at AT1 and AT2 sites. Consequently, sulfhydryl reducing agents are now used infrequently in AII receptor binding assays. In this regard, the present autoradiographic study evaluates the effects of additional peptidase inhibitors on AII receptor binding and radioligand integrity. EDTA at 5 mM enhanced binding similarly, by about 70%, at both AT1 and AT2 binding sites, whereas bacitracin (10(-4) M) did not affect binding at either site. In contrast, addition of phenanthroline and bovine serum albumin (BSA) increased binding at AT1 sites 2.3 fold, whereas binding at AT2 sites was affected minimally. Degradation of 125I [Sar1,Ile8]-AII (125I-SIAII) was determined by HPLC analysis of samples before and after incubation with tissue in each buffer. Omission of bacitracin from buffers reduced the recovery of intact radioligand to 83-87%, while recovery exceeded 94% in the presence or absence of all other buffer constituents. These results suggest that degradation of 125I-SIAII is minimal in large volume in vitro receptor autoradiography studies of rat brain AII receptors. Further, the beneficial effects on radioligand binding caused by buffer constituents such as EDTA, phenanthroline, and BSA were not due to their ability to protect the radioligand from enzymatic degradation. Because these constituents (and possibly others) had differential effects on binding with respect to receptor subtypes, caution should be used when interpreting or comparing binding data obtained from various laboratories utilizing different buffer components. PMID- 8512593 TI - Inhibition of mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase by oxacarbocyanine dyes. A structure-activity study. AB - In this study, we determined that three structurally related oxacarbocyanine dyes, 3,3'-diethyloxacarbocyanine (DiOC2(3)), 3,3'-dipentyloxacarbocyanine (DiOC5(3)), and 3,3'-dihexyloxacarbocyanine (DiOC6(3)), and one oxadicarbocyanine, 3,3'-diethyloxadicarbocyanine (DiOC2(4)), inhibit bovine heart mitochondrial NADH oxidase activity and one of them, DiOC6(3), inhibits Paracoccus denitrificans NADH oxidase activity. The mitochondrial I50 values were 9 microM (DiOC2(3)), approximately 1 microM (DiOC5(3)) and DiOC6(3)), and approximately 3 microM (DiOC2(4)), whereas the I50 value for P. denitrificans was approximately 2 microM (DiOC6(3)). Neither succinate nor cytochrome oxidase (EC 1.9.3.1) activity was inhibited significantly by any of the compounds in either electron transport chain, localizing the inhibitory site of the oxacarbocyanine dyes to the respiratory chain segment between NADH and ubiquinone. With submitochondrial particles (SMP), NADH-dependent reduction of duroquinone and coenzyme Q1 was inhibited markedly by all four compounds with DiOC6(3) being the most potent inhibitor, and the reduction of menadione was inhibited substantially by DiOC6(3). When purified complex I was used, NADH-dependent reduction of ferricyanide was inhibited by DiOC5(3) and coenzyme Q1 reduction was inhibited by all oxacarbocyanines. With P. denitrificans membrane vesicles, DiOC6(3) substantially inhibited NADH-dependent reduction of coenzyme Q1. All the oxacarbocyanines were more effective inhibitors with membrane preparations than with complex I, suggesting that membrane interactions play a role in inhibition. The mechanism of inhibition of the oxacarbocyanines appears to be similar to that of rotenone since (a) essentially only electron acceptors affected by rotenone were affected by the compounds, (b) inhibition of menadione reduction was diminished drastically with rotenone-saturated SMP, and (c) inhibition of coenzyme Q1 was largely eliminated with rotenone-insensitive complex I, and P. denitrificans membrane vesicles. PMID- 8512594 TI - Nitroxyl analogs as inhibitors of aldehyde dehydrogenase. C-nitroso compounds. AB - We previously postulated that the catalase-mediated oxidation of cyanamide leads to the formation of the unstable intermediate, N-hydroxycyanamide, which spontaneously decomposes to nitroxyl, the putative inhibitor of aldehyde dehydrogenase (EC 1.2.1.3; AlDH). Since it was not possible to provide direct evidence for the inhibition of AlDH by nitroxyl, we examined the activity of three representative substituted nitroxyls (C-nitroso compounds), viz. nitrosobenzene (NB), 1-nitrosoadamantane (NA), and 2-methyl-2-nitrosopropane (MNP), as direct inhibitors of yeast AlDH in vitro. While NB and NA were highly effective inhibitors in this system exhibiting IC50 values of 2.5 and 8.6 microM, respectively, MNP was considerably less effective with an IC50 of 0.15 mM. When tested in vivo, NA did not show any inhibitory activity on the hepatic AlDH, possibly due to the lack of site-specific delivery of the active monomeric form of this compound. However, NB at a low dose did inhibit hepatic AlDH as reflected by an increase in blood acetaldehyde levels. These results attest to the abilities of NB and NA to act as direct inhibitors of AlDH analogous to nitroxyl itself. PMID- 8512595 TI - Proliferation-dependent and -independent cytotoxicity by antitumor diarylsulfonylureas. Indication of multiple mechanisms of drug action. AB - The mechanism(s) by which antitumor diarylsulfonylureas (DSU) cause cytotoxicity has been examined in GC3/c1 human colon adenocarcinoma cells and a subline selected for resistance to N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea (ISCU). Resistance was stable in the absence of selection pressure. This mutant (designated LYC5) was 5.5-fold resistant to ISCU compared to parental GC3/c1 cells in serum containing medium when cells were exposed for 7 days. In contrast, LYC5 cells were not resistant to a 4-hr exposure to ISCU. These data indicated two possible mechanisms of action, dependent on concentration and time of exposure to ISCU. Proliferation-dependent and -independent mechanisms of cytotoxicity were identified in wild-type and resistant clones. In serum-free medium containing growth factors, the IC50 for parental cells was 0.51 microM and for LYC5 7.0 microM (13.6-fold resistance), whereas without growth factors both lines were 8- to 9-fold resistant relative to conditions of cellular proliferation. Accumulation of ISCU was similar in quiescent and proliferating cells, and was reduced only slightly in resistant LYC5 cells. Analysis of DNA by agarose gel electrophoresis showed that in GC3/c1 cells nucleosomal ladders were formed only when proliferating cells were exposed to ISCU. No nucleosomal ladders were detected in quiescent cells during exposure to toxic concentrations of drug (IC90), or after removal of ISCU and addition of serum to stimulate growth. These data indicate several mechanisms by which diarylsulfonylurea antitumor agents may cause cell death. In serum-free medium at very high concentration (IC50 approximately 370 microM) for short periods of exposure (4 hr), cytotoxicity was proliferation independent, and GC3/c1 and LYC5 cells were equally sensitive. This mechanism may relate to the uncoupling activity of ISCU. However, at pharmacological relevant concentrations, the primary mechanism was proliferation dependent and led to formation of nucleosomal DNA ladders (IC50 approximately 0.5 microM). A possible additional mechanism occurred at higher concentration (IC50 approximately 7 microM) in quiescent cells, and was not associated with DNA degradation. PMID- 8512596 TI - Affinity ligands and related agents for brain muscarinic and nicotinic cholinergic receptors. AB - This study describes the chemical synthesis and receptor binding characteristics of various affinity ligands and related ligands for brain muscarinic and nicotinic cholinergic receptors, including the 4-bromoacetamidobenzoic acid esters of dimethylaminoethanol (DMBAB) and choline (BABC) and 4 iodoacetamidobenzoylcholine (IABC). The reversible binding of [3H]3 quinuclidinylbenzilate ([3H]QNB) to calf brain membranes was inhibited in a concentration-dependent and saturable manner by DMBAB, BABC, and IABC with Ki values of 8 x 10(-7), 3 x 10(-7) and 8 x 10(-7) M, respectively; the Ki values for inhibition of reversible binding of the nicotinic ligand, [3H]methylcarbamylcholine ([3H]-MCC), were 1 x 10(-6), 6 x 10(-8), and 1 x 10(-6) M, respectively. The Ki values for irreversible inhibition of [3H]QNB binding were 8 x 10(-7), 1 x 10(-7), and 2 x 10(-7) M for DMBAB, BABC, and IABC, respectively, and for [3H]MCC binding, 8 x 10(-5), 1 x 10(-5), and 2 x 10(-5) M, respectively. Although DMBAB was found to inhibit the QNB-induced hyperactivity in mice, it did not antagonize the toxic or other pharmacologic effects of oxotremorine. Structure-activity studies with various non-affinity analogues of the 4-aminobenzoate ester of dimethylaminoethanol and choline revealed that removal of the NH2 moiety from the phenyl group increased affinity for the muscarinic but not the nicotinic cholinergic site, and quaternization of the ester side chain greatly increased affinity for the muscarinic site. Dimethylation of NH2 in 4-aminobenzoylcholine decreased the affinity for both cholinergic sites. Replacement of NH2 by NO2 increased affinity for the muscarinic but not the nicotinic site, whereas quaternization of the 4 nitrobenzoyl ester markedly increased affinity for the nicotinic site while diminishing affinity for the muscarinic site. The findings indicate that DMBAB and its analogues are useful affinity ligands for examining the biochemical and functional characteristics of brain cholinergic receptors, particularly the muscarinic which has an affinity near the nanomolar concentration range. PMID- 8512597 TI - Inhibition by SKF-525A of the aldehyde oxidase-mediated metabolism of the experimental antitumour agent acridine carboxamide. AB - Oxidation of the experimental anti-tumour agent N-[(2' dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316; acridine carboxamide) to the 9(10H)acridone, followed by ring hydroxylation and glucuronidation, appears to be the main pathway of detoxication of AC in the rat and mouse. The acridone formation has been further characterized in vitro using an enzyme enriched fraction where activity per milligram protein is increased approximately 10-fold compared with the cytosolic fraction. Inhibition by amsacrine [4'-(9 acridinylamino)methanesulphon-m-anisidide; NSC 249992] and menadione (50% inhibition at 6.4 and 1.8 microM, respectively) but not allopurinol (to 30 microM) indicates that the activity is due to aldehyde oxidase, without the involvement of xanthine oxidase. Interestingly, acridone formation in both the cytosolic and enzyme-enriched fractions is highly sensitive to the classical cytochrome P450 inhibitor SKF-525A [proadifen hydrochloride; 2' (diethylamino)ethyl 2,2-diphenylpentenoate] (50% inhibition at 9.2 and 1.9 microM, respectively). Further analysis indicates mixed non-competitive type inhibition by SKF-525A (K(is), 0.3 microM; K(ii), 4.9 microM). Little or no inhibition was seen with cimetidine, metyrapone or methimazole. No NADPH dependent acridone formation was observed with the microsomal fraction. These data indicate that acridone formation previously observed in isolated rat hepatocytes and in vivo is most likely due to aldehyde oxidase rather than cytochrome P450. PMID- 8512598 TI - Evidence that the Ca2+ inflow pathway in hepatocytes stimulated by thapsigargin is similar to that activated by vasopressin. AB - Experiments were conducted to characterize the thapsigargin-stimulated plasma membrane Ca2+ inflow pathway in hepatocytes. Ca2+ inflow was estimated by measurement of the initial rate of activation of glycogen phosphorylase a following the addition of Ca2+ to cells previously incubated in the absence of added Ca2+. Pretreatment of hepatocytes with thapsigargin caused a substantial stimulation of the rate of Ca2+ activation of glycogen phosphorylase a. This was interpreted to reflect a stimulation of plasma membrane Ca2+ inflow. The effect of thapsigargin on plasma membrane Ca2+ inflow was approximately 65% of the magnitude of the effect caused by vasopressin. When thapsigargin and vasopressin were combined as a stimulus, the degree of stimulation was similar to that caused by vasopressin alone. The thapsigargin-induced stimulation of the rate of Ca2+ activation of glycogen phosphorylase a was inhibited in a concentration-dependent manner by both Zn2+ and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl) 1H-imidazole hydrochloride (SK&F 96365). The concentration of each agent required for half-maximal inhibition was approximately 20 microM. It is concluded from: (i) the apparent lack of additivity in the responses of thapsigargin and vasopressin, and (ii) the sensitivity to inhibitors, that the Ca2+ inflow pathway in hepatocytes stimulated by thapsigargin is likely to be similar to that which is activated by vasopressin. PMID- 8512599 TI - Interindividual differences in the in vitro conjugation of methylene chloride with glutathione by cytosolic glutathione S-transferase in 22 human liver samples. AB - The interindividual variation in the in vitro conjugation of methylene chloride with glutathione by cytosolic glutathione S-transferase (GST) was investigated with 22 human liver samples. In three of the samples no activity towards methylene chloride was observed. Eleven samples showed an activity ranging from 0.20 to 0.41 (0.31 +/- 0.08) nmol/min/mg protein, and eight samples an activity of 0.82-1.23 (1.03 +/- 0.14) nmol/min/mg protein. The activities towards 1-chloro 2,4-dinitrobenzene (CDNB) of these three groups were 1.17 +/- 0.25, 1.12 +/- 0.35 and 1.20 +/- 0.53 mumol/min/mg protein, respectively. In nine of the liver samples, the alpha-, mu- and pi-class GST subunits were quantified. In two of these samples, no activity was observed towards methylene chloride, while alpha-, mu- and pi-class subunits were expressed in these human liver cytosolic samples. As the highest activity towards methylene chloride was still 1.4 times lower than the activity in rat cytosol, the existence of the three populations seems to be of little importance for human risk assessment. PMID- 8512600 TI - Effect of acetyl-L-carnitine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is believed to induce neurotoxicity by inhibiting mitochondrial oxidative metabolism, whereas acetyl-L carnitine (ALC) facilitates this process by transporting fatty acids into mitochondria for beta oxidation. We investigated whether large doses of ALC given by gavage for 1 week before and 1 week after MPTP could ameliorate MPTP neurotoxicity in mice. We found that ALC had no effect on MPTP-induced depletion of striatal dopamine and its metabolites. PMID- 8512602 TI - Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested. 1973. PMID- 8512601 TI - Lipid and lipoprotein distributions in children by ethnic group, gender, and geographic location--preliminary findings of the Child and Adolescent Trial for Cardiovascular Health (CATCH). AB - BACKGROUND: The Child and Adolescent Trial for Cardiovascular Health is a school based study designed to test the effectiveness of dietary, physical activity, and educational interventions for reducing cardiovascular disease risk and teaching healthful behaviors to children. METHODS: As part of a pilot phase in 1989, lipid, lipoprotein, and anthropometric measures were taken in black (n = 90), Hispanic (n = 68), and white (n = 265) 8- to 10-year-old schoolchildren in California, Louisiana, Minnesota, and Texas. RESULTS: There were no significant differences in mean lipoprotein cholesterol values between fasting and nonfasting children. Therefore data from fasting and nonfasting children were pooled. Males and females within the same ethnic groups had similar mean levels of total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol. However, levels of high-density lipoprotein cholesterol were higher among white and black males than among females from the same ethnic groups. Black males had higher total cholesterol than white males and higher high density lipoprotein cholesterol than white males and Hispanic males. Similarly, black females had higher high-density lipoprotein cholesterol than white and Hispanic females. In all children combined high-density lipoprotein cholesterol was inversely correlated and low-density lipoprotein cholesterol was positively correlated with subscapular and tricep skinfold thickness, weight, and body mass index. There were significant differences in mean lipoprotein cholesterol levels between geographic sites. Total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were highest in children from California followed by children from Texas, Minnesota, and Louisiana. CONCLUSION: Our results suggest that body fatness total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol differ in children by gender, ethnicity, and geographic location. PMID- 8512603 TI - The Nightingale Pledge: a commitment that survives the passage of time. PMID- 8512604 TI - Systems analysis of an occupational health department: recommendations to increase effectiveness. AB - The author analyzes the occupational health department of an urban health maintenance organization using systems theory. The framework for the analysis includes the environment, inputs, throughputs, outputs, evaluation, and forces of entropy and negentropy, as well as stresses and strains. Recommendations to increase the effectiveness of the department are based on the analysis. Any occupational health department could benefit from a similar analysis. PMID- 8512605 TI - Evaluation of a unique mechanical client lift: efficiency and perspectives of nursing staff. AB - This study evaluated the acceptability of a mechanical client lift based on the design employed for helicopter rescue lifts. Twenty-three nursing personnel completed questionnaires which explored their preferences, intentions to use the lift, perceptions of helpfulness, and exertion. Sixteen clients in a long term care setting consented to participate. One hundred manual lifts and 100 belt lifts were observed for comparative time and staff measures. The findings suggest that: 1) nursing staff will prefer the belt lift device for changing incontinent briefs; 2) nursing staff will prefer the belt lift device for toileting; 3) nursing staff will prefer the belt lift device to the currently used lift (in cases where either lift is appropriate) for bed/chair transfer; and, 5) the time required to utilize the belt lift as compared to manual lifting methods will not increase significantly. PMID- 8512606 TI - Women in nontraditional jobs: is there a risk for musculoskeletal injury? AB - More females are entering once male dominated jobs that require physical strength, flexibility, and endurance. Musculoskeletal injuries, a leading cause of worker disability, occur more frequently when the physical demands of a job exceed the worker's physical capabilities. Although women are more flexible than men, differences in muscle mass, body composition, and size can place women at risk for injury. The risk for musculoskeletal injury can be reduced through ergonomic considerations and physical fitness. PMID- 8512607 TI - Request for medical evaluation: an approach for on-site occupational health professionals. AB - The role of the occupational health professional in determining fitness for duty is expanding. Proper determination of fitness for duty diffuses acute situations in the workplace. The occupational health professional's role is nonjudgmental and objective. This protocol protects the occupational health service from punitive actions. PMID- 8512608 TI - Social learning theory: strategies for health promotion. AB - Occupational health nurses can facilitate the design of more effective health promotion programs by utilizing theories of behavior change. Planning a health promotion program based on the Social Learning Theory includes an assessment of personal as well as environmental factors that influence behavior. The motivation of employees to make behavior changes can be enhanced by raising their awareness of the problem, engaging clients in the process of goal setting, and making self satisfaction conditional on a certain level of performance. Goal setting with attainable subgoals creates and sustains self-motivation, which can lead to larger, future goals. Interpreting the consequences of health behavior can be an incentive for individuals who value the perceived effects of lifestyle changes. PMID- 8512609 TI - Update on the Americans with Disabilities Act for occupational health nurses. PMID- 8512610 TI - Heat stress: its effect and control. AB - Heat cramps, heat exhaustion, and heat stroke are major disorders resulting from the body's reaction to overexposure to hot environments. Physiological and psychological adaptation to hot environments--acclimatization--can improve heat tolerance. A number of measures determine the environmental contributions to heat stress. The occupational health nurse can establish priorities for addressing the work related health needs of workers in hot environments. PMID- 8512611 TI - Exercising at work: barriers to women's participation. AB - Only a minority of women in an urban random sample have the opportunity to exercise at work, and even fewer women use these opportunities. Lack of time and inconvenient times are the major reasons for not participating in exercise programs at work. Exercise programs at work are used by women who are already physically active, suggesting that workplace exercise programs do not serve the needs of women who may need exercise programs most. Multivariate analysis shows that age, having children, lack of energy, and lack of support are significant barriers to women's exercise participation at work. The results of this study suggest a leadership opportunity for on site occupational health nurses in addressing these barriers to workplace exercise. PMID- 8512612 TI - Back health: development of a risk assessment tool. AB - Back injuries are one of the most significant industrial liabilities, resulting in increased absenteeism, costly medical expenses, and often employee disability. The authors present a reliable and valid back health risk assessment tool to measure predisposition for back injuries. The tool was developed with the collaboration of members of a local constituent association. The tool can be implemented by routine interviews with workers. Occupational health nurses can use the tool to diagnose and possibly alleviate back injuries in workers. Use of the tool will help to further define the characteristics for the potential for back injury. PMID- 8512613 TI - Occupational health nursing in Portugal. AB - Portugal has approximately 10 million inhabitants of which, in 1991, 4,625,200 were employed. The main causes of death are circulatory system illnesses and malignant tumors. The most common occupational diseases are pneumoconiosis, work induced hearing loss, and contact dermatitis. In 1991 1% of the 304,636 occupational accidents were fatal. The majority of Portuguese enterprises have no occupational health services, although occupational health services rules have existed since 1967. The estimated 1,500 occupational health nurses in different roles do not have specialized training; however, as a member of the EC, Portugal will adhere to whatever is accepted in this field. PMID- 8512614 TI - Managing time. AB - Managing time puts the occupational health nurse manager in control of health services and personal goals. Articulating those goals and appropriately delegating some of the outcomes needed to meet those goals should result in accomplishing the goals in less time. Strategies to control time expenditures on a daily basis include developing a "to do" list, avoiding procrastination, time wasters, and paper shuffling, creating an environment conducive to work, and rewarding self and staff for a job well done. PMID- 8512615 TI - Preventing slips, trips, and falls in the workplace. PMID- 8512616 TI - Protein modifications in the D2 protein of photosystem II affect properties of the QB/herbicide-binding environment. AB - The D2 protein contains an extended loop (the D-de loop) between helices D and de at the reducing side of photosystem II (PS II). Characterization of D2 mutants of the cyanobacterium Synechocystis sp. PCC 6803 has indicated that the length and amino acid composition of the D-de loop are not critical for basic PS II functions, although most of the residues in that region are conserved phylogenetically. Here we show using herbicide binding and electron-flow inhibition measurements that drastic modifications in the D-de loop of the D2 protein modify the interaction of some PS II-directed herbicides with their binding niche. The stability of (semi)-reduced QB in its binding pocket is altered in at least two of the mutants, as indicated by a shifted peak temperature of the thermoluminescence signal originating from charge recombination involving QB. These results suggest a close functional association between the D-de loop of the D2 protein and the QB/herbicide-binding environment, which is viewed as being coordinated mostly by residues of the D1 protein. This represents one of the first examples of modification of the QB/herbicide-binding domain by mutations in the D2 protein. PMID- 8512617 TI - Mutational analysis of the PsbL protein of photosystem II in the cyanobacterium Synechocystis sp. PCC 6803. AB - The psbL gene is a member of the psbEFLJ gene cluster in the cyanobacterium Synechocystis sp. PCC 6803 and higher plants. psbL, a 4.5 kDa protein encoded by this gene, is a component of the photosystem II complex. The amino acid sequence of this protein indicates that it has a single membrane-spanning alpha-helical domain. We have used a targeted mutagenesis technique to delete the coding region of the psbL gene in Synechocystis 6803. The resultant mutant strain T345 did not show any PSII-mediated oxygen evolution activity and, as a result, could not grow under photoautotrophic conditions. However, it had normal PSI activity. The chlorophyll to phycobilin ratio in the T345 cells was significantly lower than that in the wild type cells. Fluorescence emission spectra (77 K) of the mutant cells showed the absence of a 695 nm band that usually originates from the PSII complex. Binding assays with radioactive diuron demonstrated that the mutant cells did not have any herbicide binding activity. However, immunostaining experiments showed that both the D 1 (the herbicide binding protein) and the D2 proteins of the PSII reaction center were present at > 25% of their normal levels in the thylakoid membranes of the T345 mutant cells. Our data indicate that the PsbL protein is essential for the normal functioning of PSII. PMID- 8512618 TI - Molecular modelling of the interaction between DCMU and QB-binding site of photosystem II. AB - The preferred binding orientations for the herbicide DCMU within the QB-binding of the D1 protein model from a photosystem II reaction centre have been determined. Calculation of the intermolecular energy between the herbicide and the binding site has been instrumental in obtaining optimum positions reinforced by experimental results from mutation studies and herbicide binding to analogous bacterial reaction centres. We have shown that two binding sites are possible, one involving a hydrogen bond to the His 215 residue of the QB-binding site and the other to the Ser 264 residue. In both cases, it appears to be the van der Waals forces which are more important for the stabilization of the interactions. PMID- 8512619 TI - Before they called it psychopharmacology. PMID- 8512620 TI - Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. AB - Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [3H]cyano-imipramine ([3H]CN-IMI), the 5-HT1A receptor with [3H]8-hydroxy-2-[di-n propyl-amino]tetralin ([3H]8-OH-DPAT), and the 5-HT2 receptor with both [3H]ketanserin and [125I]lysergic acid diethylamide ([125I]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5 HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific. PMID- 8512621 TI - Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. AB - Like fluoxetine, the N-demethylated metabolite norfluoxetine exists in R- and S enantiomeric forms. S-Norfluoxetine inhibited serotonin (5-HT) uptake and [3H]paroxetine binding to 5-HT uptake sites with a pKi of 7.86 and 8.88 or 14 and 1.3 nM, respectively, whereas R-norfluoxetine was 22 and 20 times, respectively, less potent. R- and S-Norfluoxetine were less potent than the corresponding enantiomers of fluoxetine as inhibitors of norepinephrine uptake and [3H]tomoxetine binding to norepinephrine uptake sites. Ex vivo studies showed that S-norfluoxetine inhibited 5-HT uptake with an ED50 of 3 mg/kg intraperitoneally, 4.7 mg/kg subcutaneously, and 9 mg/kg orally (7.3, 11.4 and 21.9 mumol/kg, respectively), while the ED50 for R-norfluoxetine exceeded 20 mg/kg intraperitoneally (48.6 mumol/kg). Inhibition of 5-HT uptake in cerebral cortex ex vivo and decrease in 5-HIAA levels in hypothalamus persisted for 24 hours after administration of S-norfluoxetine as demonstrated with the administration of fluoxetine. Thus, S-norfluoxetine is the active N-demethylated metabolite responsible for the persistently potent and selective inhibition of 5 HT uptake in vivo. PMID- 8512622 TI - Ethanol-induced alterations in electroencephalographic activity in adult males. AB - The present investigation examined the effects of placebo (P), low-dose (LD), and high-dose (HD) ethanol on electroencephalographic (EEG) activity in 21 healthy, adult males (X = 22.7 years). Only one condition (P, LD, or HD) was presented per day and the condition order was randomized. For each subject, blood-alcohol levels measured via breathalyzer and EEG activity, using the entire 10/20 International System, were recorded both prior to and at intervals of 35, 70, 105, and 140 minutes after P, LD, or HD administration. The Fast Fourier Transform was used to calculate power spectral densities for each EEG recording. Measures of the relative areas under the power spectral curve were made for each of the following frequency bands: slow alpha (7.5 to 10 Hz); fast alpha (10.5 to 13.0 Hz); slow beta (13.5 to 19.5 Hz); and fast beta (20 to 26 Hz) at electrodes F3, F4, C3, C4, P3, P4, O1, and O2. Repeated-measures multivariate analysis of variance performed on normalized relative area values revealed that ethanol had significant effects on EEG activity at anterior sites: frontal (F3, F4) and central (C3, C4) that presented as increased activity in the slow alpha frequency band. These results suggest a differential responsivity of both cortical region and EEG frequency band to the effects of ethanol ingestion. PMID- 8512623 TI - Modulation of central cholinergic activity by GABA and serotonin: PET studies with 11C-benztropine in primates. AB - The pharmacologic treatment of many neuropsychiatric disorders (Alzheimer's disease, schizophrenia, depressive illness) has been targeted at the central hypothesis that defects in a single neurotransmitter system underlie the pathophysiology of the disease state. With the recognition that such treatments have not been efficacious consistently, recent drug development has been directed at altering other functionally linked neurotransmitters involved in these diseases. Using positron emission tomography, we have noninvasively investigated the effects of two noncholinergic drugs on the release of acetylcholine. By examining the effects of gamma-vinyl gamma-aminobutyric acid (GABA) (a GABA transaminase inhibitor) or altanserin (a serotonergic antagonist) on the regional binding of 11C-benztropine in the primate brain (Papio anubis), we demonstrated that drugs acting upon either GABAergic or serotonergic neurons produce profound regional changes in acetylcholine release. These findings indicate that the mechanisms of action and the subsequent therapeutic efficacy of these centrally acting drugs may be linked to their multitransmitter effects. This application of positron emission tomography represents an extremely promising experimental approach that can be directed towards elucidating abnormalities in neurotransmitter modulation relevant to disease progression and pharmacologic treatment. PMID- 8512624 TI - Effects of acute stimulant medication on cerebral metabolism in adults with hyperactivity. AB - Recent work in our laboratory has demonstrated both global and regional reductions in cerebral glucose metabolism in adult subjects with attention deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine the effects of an acute dose of stimulant medication on cerebral metabolism in adults with ADHD using positron emission tomography with fluorodeoxyglucose-18 as the tracer. Each subject underwent scanning twice, once off-drug and again after receiving a single oral dose of either dextroamphetamine (0.25 mg/kg) or methylphenidate (0.35 mg/kg). Subjects completed behavioral self report measures before and after the scan and performed an auditory continuous performance task during the tracer uptake period. Neither drug changed global metabolism. Both drugs increased systolic blood pressure, and dextroamphetamine improved performance on the auditory attention task. Each stimulant produced a differential pattern of increases and decreases in regional metabolism throughout the regions of interest that were sampled. Rather than increasing glucose utilization in specific brain regions with lowered metabolic rates in adults with ADHD, stimulants may act by altering glucose use throughout the brain. PMID- 8512625 TI - The combination of VIP and atropine induces REM sleep in cats rendered insomniac by PCPA. AB - Twenty-four cats were implanted with electrodes for chronic sleep recordings. One week after the surgery, cats were treated with two intraperitoneal injections of parachlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, to induce insomnia. Twenty-four hours after the second injection of PCPA, cats were at the peak of insomnia (strong reduction of both slow wave sleep 2 and rapid-eye movement [REM] sleep). During this period cats were divided into four groups (n = 6) and were injected with either atropine (0.5 mg/kg, IM [3.5 mmol/kg]), vasoactive intestinal peptide (VIP) (200 ng, ICV [60 pmol]) or atropine plus VIP (same doses and routes of administration). The control group received saline intramuscularly (IM) intracerebroventricularly and (ICV). Results showed that VIP and atropine injected alone and in combination increased mean total time of REM sleep in PCPA-treated animals. These findings are discussed in terms of a serotonin-acetylcholine interaction. PMID- 8512626 TI - Memory complaint, memory performance, and psychiatric diagnosis: a community study. AB - This study examined the prevalence of memory complaint and poor memory performance on brief screening measures within a community sample of 810 adults. All individuals received an extensive household interview and a clinical psychiatric evaluation. Overall, 22% indicated that they currently had trouble with their memory. This percentage increased with age, rising to 43% for those 65 to 74 years old, 51% for those 75 to 84 years old, and 88% for those 85 years of age and older; the percentage indicating memory problems decreased with educational attainment. The prevalence of poor memory performance was 11%, also increasing with less education and increased age, rising to 26% for those 65 to 74 years old and to 40% for those older then 75. Those who complained of memory trouble were twice as likely to show poor memory performance (29%) compared with those who did not complain (15%). Multivariate analysis found age, emotional distress, and physical illness to be independent predictors of memory complaint; age, functional disability, education, and physical illnesses proved to be independently associated with poor memory performance. A higher prevalence of complaints of memory trouble was found not only for those with affective disorders, as might be expected, but also among those with schizophrenic, cognitive, anxiety, and adjustment disorders. However, only individuals with cognitive disorders showed a higher prevalence of poor memory performance. PMID- 8512627 TI - Successful treatment with captopril of an elderly man with polydipsia and hyponatremia. AB - A case of severe hyponatremia in a polydipsic 64-year-old man is described. He was unsuccessfully treated with both demeclocycline and lithium carbonate. However, low-dose captopril reversed the polydipsia and resulted in sustained normal serum sodium levels. We believe the antidipsogenic effect of captopril may benefit some patients with polydipsia and hyponatremia. PMID- 8512628 TI - Evaluation of multiple doses of milacemide in the treatment of senile dementia of the Alzheimer's type. AB - A multicenter, double-blind, placebo-controlled, parallel group study was conducted to assess the safety and efficacy of three doses of milacemide in the treatment of patients with senile dementia of the Alzheimer type of mild to moderate severity. Patients were randomly assigned to receive one of three dosages of milacemide (400, 800, or 1200 mg/day) or placebo for 4 weeks followed by a single-blind 4-week placebo period. One hundred forty-eight men and women older than 50 years of age were enrolled, and 129 patients completed the study. The differences among treatment groups were not statistically different with respect to total scores on the Alzheimer's Disease Assessment Scale or any items and subscales that were examined, nor were significant differences on the Clinical Global Impression Scale found. Clinically significant increases in liver function tests, specifically aspartate aminotransferase and alanine aminotransferase (AST and ALT), were reported for five of the patients receiving milacemide, requiring their withdrawal from the study. PMID- 8512629 TI - The prevalence of late-onset schizophrenia in a psychogeriatric population. AB - Of 288 patients admitted to our psychogeriatric unit during a 4-year study, seven patients were diagnosed as having symptoms of paranoid schizophrenia (2.4% of all admissions). All the patients were women. Their symptoms included bizarre delusions and auditory hallucinations. Negative symptoms were rare. Attempts to reduce the dosage of neuroleptic medication led to reappearance of the symptoms in six patients and readmission of the seventh. PMID- 8512630 TI - Dementia in a population-based study. PMID- 8512631 TI - Alzheimer's disease: headlines, confusion, and the unknown. PMID- 8512632 TI - Acute care of the African American elder. PMID- 8512633 TI - Delayed late component of visual global field power in probable Alzheimer's disease. AB - A substantial literature shows that late components of visual evoked potentials (VEPs) are delayed in at least some forms of dementia in the elderly. The late component delay is selective in that earlier components are not affected. More recent work with better defined clinical groups suggests that the selective late component delay may be characteristic of Alzheimer's disease (AD) rather than an inevitable feature of dementia in general. To overcome problems in traditional VEP component latency measurement the present study uses reference-free Global Field Power (GFP) analysis to more objectively define VEP components and finds that the GFP peak corresponding to the late P2 component of the flash VEP is delayed in a probable AD group but not in a demented unlikely AD group, relative to age-equivalent healthy controls. The late-component delay is again found to be selective in that the GFP peak corresponding to the earlier P1 component of the flash VEP does not differ between groups. These findings further strengthen the evidence for electrocortical changes in the visual system of AD patients. PMID- 8512634 TI - The nature and time course of cognitive side effects during electroconvulsive therapy in the elderly. AB - Cognitive and clinical changes during hospitalization were examined in 48 elderly patients with major depression treated with electroconvulsive therapy (ECT) and 55 elderly depressed patients not treated with ECT. Cognitive changes with ECT involved orientation, attention and calculation, and recall. The maximal decrement during ECT averaged 3 points on the Mini-Mental State Examination and occurred after two thirds of the treatments were administered. Baseline cognitive values returned by time of discharge. The affective symptoms improved throughout the course of treatment and remained improved while cognition returned to normal. Patients not receiving ECT showed slightly improved cognitive performance during hospitalization and small, gradual, clinical improvement. PMID- 8512635 TI - A two-year longitudinal study of cognitive function in normal aging and Alzheimer's disease. AB - A group of 136 elderly subjects were administered a comprehensive neuropsychological test battery, which was readministered 2 years later. Among the 136 elderly subjects, 86 were assigned a diagnosis of probable Alzheimer's disease. An additional 33 young subjects were administered the assessment battery at baseline only. The normal elderly group exhibited no decline in cognitive test performance over the 2-year follow-up interval. Subjects with mild cognitive impairment, however, were as likely to deteriorate between baseline and follow-up as the more severely impaired subjects. The tests that exhibited longitudinal decline in the Alzheimer's disease patients constituted a subset of the tests that revealed cross-sectional deficits relative to the normal elderly. Differences in baseline cognitive test performance and in rate of cognitive deterioration were examined in relatively young versus relatively old Alzheimer's disease patients. Potential psychometric predictors of cognitive decline in the normal elderly were identified. PMID- 8512636 TI - Microanalysis of senile plaques using nuclear microscopy. AB - Silver-staining "senile" plaques occurring in the brain are a major part of the pathology of Alzheimer's disease. The elemental composition of these structures, and the possible presence of aluminum and silicon in these structures, has been the subject of an increasing research effort over the last decade. However, the results have often been contradictory. Using a scanning proton microprobe, the elemental composition of senile plaques has been determined. This instrument, similar to an electron probe, uses a focused beam of protons scanned across a sample to map the elements. The technique is absolutely quantitative and is sensitive down to the parts per million level. Tissue from six cases of clinically and pathologically characterized cases of Alzheimer's disease and two aged neurologically normal controls was scanned. It was found that aluminum and silicon occur at a level of 50 ppm or greater in the cores of 20% of senile plaques and that the total occurrence of aluminum or silicon in scans containing plaques was not above background. The major uncertainties affecting interpretation of results of this kind are discussed, and it is suggested that the least controllable factor is contamination in the reagents used to prepare and stain the tissue. This indicates that until plaques can be unambiguously identified and analyzed in untreated tissue, no conclusion can be reached on whether senile plaques contain aluminum and silicon. PMID- 8512639 TI - Reproductive genetic services in rural Oklahoma. AB - The system of reproductive care as it relates to genetic services for women in rural Oklahoma is addressed. Description of reproductive services and genetic reproductive services for rural women is described and barriers to accessing reproductive genetic care are identified. The barriers and any progress that has been made in breaking these barriers will be described under four general categories: (1) financial barriers; (2) system capacity barriers; (3) organizational practices and atmosphere of services, and (4) cultural, personal and other system barriers. PMID- 8512644 TI - Prenatal genetic testing and geneticization: mother matters for all. AB - Prenatal genetic testing represents the most widespread human application of reproductive technology, and its use is necessarily gendered. Moreover, its application both reflects and generates the process of 'geneticization' that increasingly orients contemporary western-world stories of health and disease. Taking a woman-centered approach, this paper examines some of the stories being told about testing; questions their themes of 'reassurance' and 'choice', their construction of 'risk', and their assumptions about disability; and explores the 'life-style' testing creates for (pregnant) women. Testing itself, and its power to control how we live and the children we bear, raises complex and troubling matters that require continued and fresh examination. PMID- 8512648 TI - Primary care physicians as providers of frontline genetic services. AB - Due in part to shortages of health care professionals with expertise in genetics, primary care physicians will assume a greater role in providing frontline genetic services as genetic tests for more diseases become available. I report some preliminary findings from a national survey of primary care physicians, psychiatrists, medical geneticists and genetic counselors. As expected, no group of nongenetics specialists had as much knowledge as geneticists. Nongeneticist physicians with the greatest exposure to patients with genetic problems had more knowledge than physicians without such exposure. Non-geneticist physicians were more likely to be directive in counseling than geneticists. Problems for future research are enumerated. PMID- 8512649 TI - Training in human genetics in the United States. AB - A national study of existing and future human resource needs in the field of human genetics has never been conducted. Published figures of the existing levels of human genetics training are not available. This report reviews the current status of graduate training in human genetics in the US. Issues of certification, accreditation, enrollment and recommendations for future training needs are also discussed. As of 1989, 109 US programs offered training at the graduate or postgraduate level in human genetics. Sixty-seven percent were degree-granting programs. A 20% increase in the number of programs occurred between 1985 and 1989. In contrast, the number of graduates increased by only 10.5%. Reasons for this decreased level of training productivity remain undefined. PMID- 8512650 TI - Reproductive genetic testing: implications for nursing education. AB - Reproductive genetic testing technologies are expanding at an exponential rate. Nurses are increasingly being called upon to provide these services to women. This paper discusses the status of nursing education in genetics and identifies immediate needs for nurses in order to be adequately prepared to respond to these increased demands. The future role of nurses in providing genetic services is delineated. PMID- 8512651 TI - The impact of prenatal genetic testing on quality of life in women. AB - The techniques of prenatal genetic diagnosis are being used with increasing frequency in the provision of prenatal care. One aim of such testing is to benefit pregnant women. Inadequate data exist, however, to indicate whether testing provides benefits for or imposes burdens upon the women involved. The influence of testing on anxiety during pregnancy, on a woman's sense of control over the progress and outcome of pregnancy, and on a woman's relationships with her partner and future child are all of concern. Investigation of these questions should be integral to studies undertaken to assess prenatal genetic testing. PMID- 8512654 TI - Prenatal screening and its impact on persons with disabilities. AB - This paper examines and describes the perspective of persons with disabilities regarding the policy implications of prenatal screening. The most troubling, and controversial, aspect is when screening results in selective abortion. Persons with disabilities have a unique perspective on both sides of the public argument over abortion. The most common reasons given for selective abortions because of disability are based on assumptions that have, mostly, not been affirmed or refuted through research. The impact of the availability of prenatal testing on public attitudes about disability and practices towards disabled persons should be explored. Additional input from disabled people is needed. PMID- 8512657 TI - Long-term effects of the angiotensin converting enzyme inhibitor captopril on metabolic control in non-insulin-dependent diabetes mellitus. AB - The role of angiotensin converting enzyme (ACE) inhibitors in improving insulin mediated glucose uptake has been described. However, their effects on long-term glucose control in diabetes mellitus are less well established. This study examines the effect of 4 months of captopril treatment on blood pressure (BP) and glucose control in 130 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. Therapy for glycemic control was adjusted during a 3 month period prior to entry into active BP treatment and was not changed during 4 months of captopril administration. Fasting blood glucose and sitting BP were measured before and at 1, 2, 3, and 4 months of captopril monotherapy. Hemoglobin (Hb) A1c, serum electrolytes, creatinine, total cholesterol, and triglycerides were measured before and at 4 months. There were significant reductions in fasting blood glucose from baseline at 1 month (P < .01) and further stepwise decreases in values at 2, 3, and 4 months. Differences in glucose from month to month were highly significant. HbA1c was stable over a 3-month pretrial period, then decreased (P < .001) from baseline at 4 months of active treatment. Mean serum potassium increased from 4.4 to 4.7 (P < .001) at month 4 and there was an inverse correlation (r = -0.2, P < .025) between changes in potassium and HbA1c. Total serum cholesterol fell (P < .01) at month 4 of treatment. Serum creatinine and blood urea were unchanged, but of 18 patients with mild proteinuria pretrial, 12 of 18 were negative for protein at 4 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512658 TI - A kallikrein-like enzyme in human vascular tissue. AB - We attempted to identify the presence of kallikrein in human vascular tissue obtained from patients undergoing surgery. Sections of thoracic (n = 9) and abdominal aorta (n = 6), renal artery (n = 6), and saphenous vein (n = 17) were rinsed with 0.01 mol/L Tris-HCl buffer, cleaned, minced, and homogenized at 4 degrees C. The homogenates were centrifuged and supernatants were assayed for protein content and for active and total (trypsin activation) enzymatic activity on the peptide H-D-Val-Leu-Arg-paranitroanilide (S2266), a synthetic substrate for glandular kallikrein. Enzymatic activity was inhibited by aprotinin and polyclonal antibodies against human glandular kallikrein. Kallikrein was resistant to soybean trypsin inhibitor and had an optimum pH of 8.2. A significant correlation was found between the amidolytic and kininogenase activities measured on S2266 and dog kininogen, respectively (r = 0.83, P < .01). The kallikrein-like enzyme was present mainly in the inactive form. Higher levels were found in the homogenates of renal artery (active: 190 +/- 36, total: 5036 +/ 908 pkat/g protein) than in those of thoracic (active: 38 +/- 9, total: 973 +/- 350 pkat/g protein) and abdominal aorta (active: 44 +/- 10, total: 3031 +/- 709 pkat/g protein). In the homogenates of saphenous vein, active and total enzymatic activities averaged 188 +/- 90 and 2003 +/- 450 pkat/g protein, respectively. A significant inverse correlation was found between the levels of total enzymatic activity in saphenous vein homogenates and mean blood pressure values (r = 0.78, P < .005). These results suggest that a kallikrein-like enzyme is present in human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512659 TI - Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension. AB - Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo ( 10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512660 TI - Atrial natriuretic factor potentiating and hemodynamic effects of SCH 42495, a new, neutral metalloendopeptidase inhibitor. AB - Neutral metalloendopeptidase (NEP) inhibitors delay atrial natriuretic factor (ANF) catabolism and potentiate biological responses to ANF. We describe biochemical and pharmacological profiles of a novel NEP inhibitor, SCH 42354 (N [2(S)-(mercaptomethyl)-3-(2-methylphenyl)-4-oxopropyl]-L-methionine and its orally active ethylester prodrug, SCH 42495. SCH 42354 selectively inhibited hydrolysis of leu-enkephalin and ANF (IC50 of 8.3 and 10.0 nmol/L, respectively) in vitro. Plasma levels of exogenous ANF were augmented and ANF clearance from plasma was delayed by oral SCH 42495 (3 to 30 mg/kg) in normotensive rats. Plasma ANF levels in volume expanded rats were higher in SCH 42495-treated rats. Diuretic and natriuretic effects of ANF were increased in rats treated with SCH 42495. Oral doses of 1, 3, or 10 mg/kg of SCH 42495 produced significant reductions in blood pressure in DOCA-Na hypertensive rats of 22 +/- 6, 43 +/- 7, and 62 +/- 12 mm Hg, respectively, which were not associated with increases in heart rate. These doses did not alter urine flow, salt excretion, or plasma ANF. SCH 42495 produced significant elevation of urinary excretion of ANF and cGMP. In Dahl-S hypertensive rats, SCH 42495 (1 to 10 mg/kg orally) produced falls in blood pressure of a magnitude similar to that observed in DOCA-Na hypertensive rats. Significant hypotensive activity was observed 18 h after a single 10 mg/kg oral dose in Dahl-S hypertensive rats. In DOCA-Na hypertensive rats, a single dose of SCH 42495 significantly decreased cardiac output and did not lower systemic vascular resistance, a profile similar to that of ANF. The hypotensive response to SCH 42495 was not ascribable to ACE inhibition. Pithed rat preparations revealed no interaction of the drug with autonomic cardiovascular function. The antihypertensive effect of SCH 42495 likely results from potentiation of endogenous ANF via NEP inhibition. PMID- 8512661 TI - Contrasting effects of epinephrine on forearm hemodynamics and arterial plasma norepinephrine. AB - Circulating catecholamines are widely considered to cause vasoconstriction. However, in the present study an intravenous infusion of 0.01 micrograms/kg/min epinephrine for 10 min in healthy men (n = 40, 20 to 40 years of age), which raised arterial plasma epinephrine from 100 +/- 13 to 231 +/- 22 pg/mL (mean +/- SE), increased forearm blood flow (FBF) from 2.79 +/- 0.17 to 3.45 +/- 0.25 mL/100 forearm tissue/min (P < .001), and decreased forearm vascular resistance (FVR) from 37.0 +/- 2.4 to 31.1 +/- 2.1 (arbitrary units). Further stepwise increase in epinephrine infusion rate progressively raised FBF (to a maximum 6.91 +/- 0.46) and decreased FVR (to minimum 16.7 +/- 2.0), and increased arterial plasma norepinephrine by more than 60% (P < .001). Thus, circulating epinephrine in concentrations that can be produced by mental stress has, despite its ability to increase sympathetic drive, a regional vasodilating effect in the human forearm. PMID- 8512662 TI - Positive correlation between the blood pressure and heart rate response to the cold pressor test and the environmental temperature in older hypertensives. AB - The aims of our study were to evaluate whether there is any relationship between the environmental temperature and the response to the cold pressor test and if this relationship is different in younger and older hypertensive patients. We studied 100 mild-to-moderate hypertensives, aged 21 to 75 years. In the > or = 45 years group (46 patients) a significant positive correlation between the environmental temperature and the heart rate and blood pressure response to the cold pressor test was found. The relative humidity was not correlated with the response to the cold pressor test, but multiplying the mean temperature and the mean relative humidity enhanced the correlations of the environmental temperature. An increase in the mean temperature for the 20 days before the cold pressor test (the best correlated period) by 10 degrees C correlated with increases in the systolic blood pressure response by 10.5 mm Hg (P = .0195), the diastolic blood pressure response by 8 mmHg (P = .0079), the mean blood pressure by 9 mmHg (P = .0058), and the heart rate response by 3.8 beats/min (P = .0134). In < 45 years patients no environmental relationship of the response to cold pressor test was found. A chronic exposure to low temperatures is correlated with higher blood pressure levels--as previously reported--and, in contrast (but only in elderly), with a lower blood pressure response to acute cold stress. Our findings confirm the higher meteorological dependence of hemodynamics in the elderly, and suggest that the research protocols using the cold pressor test should adjust the response for the previous environmental temperature. PMID- 8512663 TI - On the vascular inotropic action of 1,25-(OH)2 vitamin D3. AB - Previous work from our laboratory showed that injection of 1,25-(OH)2 vitamin D3 (1,25-vitD) into the rat over a 3-day period increases force generating capacity of subsequently isolated resistance arteries. To better understand the mechanism of this vascular inotropic action, we examined the time course of its development and Ca(2+)-associated mechanism of action. Mesenteric resistance arteries were isolated from 12-week-old male spontaneously hypertensive rats (SHR) 6 and 24 h after a single injection and 24 h after three and seven consecutive days of injection of 1,25-vitD (20 ng/100 g) or vehicle. Serum 1,25-vitD was increased nearly threefold at 6 h, but not at later times. Serum total and ionized Ca2+ were not affected at any time point. No changes in contractile force generation were detected at 6 and 24 h, but a significant increase in the active stress response to norepinephrine and arginine vasopressin was observed after both 3 and 7 days of 1,25-vitD treatment. No effect on sensitivity to either agonist was observed at any time point. To determine whether the vascular inotropic effects of 1,25-vitD might translate into changes in blood pressure, 11-week-old male Wistar rats were given daily injections of 1,25-vitD (20 ng/100 g) over a 4-week period, and blood pressure and body weight were measured. While body weight did not differ at any time point in the two groups, systolic blood pressure was elevated in the 1,25-vitD group v control by 7 days, and continued to be elevated over the period of observation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512664 TI - Do thymic-neuroendocrine interactions play a role in the antihypertensive effect of neonatal thymectomy in Lyon hypertensive rats? AB - Previous studies showed that neonatal thymectomy prevented the spontaneous increase in blood pressure in genetically hypertensive rats (LH) of the Lyon strain, leaving untouched that of their normotensive controls (LN). As the thymus is connected to the neuroendocrine system through secretion of hormonal factors, we investigated the possible role played by these factors in hypertension of LH rats. To that end we studied, in sham-operated and neonatally thymectomized LH rats, the blood pressure effects of thymostimulin, a partially purified thymus extract and examined whether changes in major neuroendocrine factors of blood pressure regulation occurred in thymectomized LH rats. Thymostimulin (1 or 10 mg/kg/48 h) did not modify blood pressure in sham-operated LH rats and failed to consistently increase it in neonatally thymectomized animals. Urinary mineralocorticoids, catecholamines and their metabolites, and plasma renin levels were not altered by neonatal thymectomy. Plasma testosterone was decreased to a similar degree by neonatal thymectomy in LH and normotensive controls. These results do not favor a pressor role of thymic hormonal factors in LH rats and show that the antihypertensive effect of neonatal thymectomy is not secondary to a decreased secretion of catecholamines, renin, mineralocorticoids, and testosterone. They therefore suggest that the role of the thymus in genetically hypertensive LH rats is more likely mediated by cellular immune mechanisms than by hormonal processes. PMID- 8512666 TI - Increased prevalence of cardiovascular complications in women with furosemide resistant essential hypertension. AB - Patients with essential hypertension (n = 2969) who had not been taking any blood pressure medication for longer than 1 week were classified as furosemide sensitive (FS) if their diastolic BP after furosemide fell > or = 10% and furosemide-resistant (FR) if it fell less than that. The FS group was significantly (P < or = .05) older, and had higher blood pressure than the FR group. In patients over age 50, the prevalence of cardiovascular complications (myocardial infarction, stroke, angina, congestive heart failure, and intermittent claudication) in the FR group (12.3%) was significantly (P = .0039) more than in the FS group for all patients, and especially for women (P = .0053). This was not explained by plasma renin activity, plasma norepinephrine, obesity index, cholesterol, blood sugar, or smoking history, and was associated in the FR group with a lower BP. This study characterizes the furosemide response of BP in hypertensive subjects and demonstrates an increased prevalence of cardiovascular complications in women over age 50 in the furosemide resistant group. PMID- 8512667 TI - Impact of diabetes on sodium-lithium countertransport in pregnancy-induced hypertension. AB - The purpose of this study was to assess the impact of type I diabetes on sodium lithium countertransport (CTT) in normotensive third trimester women and those with pregnancy-induced hypertension (PIH). CTT was measured in the following groups: nonpregnant diabetic and nondiabetic women, pregnant nondiabetics with and without PIH, and pregnant diabetics with and without PIH. CTT was determined as external sodium-stimulated lithium efflux from lithium loaded red cells [mmoles/liter of cells x hours = units (U)]. In the nonpregnant state, nondiabetics and diabetics demonstrated similar CTT activity (0.20 +/- 0.02 U, n = 22, v 0.26 +/- 0.03 U, n = 18). In pregnancy, normotensive nondiabetics and diabetics had CTT activity similar to each other, the values of both being significantly higher than those in nonpregnant women (0.39 +/- 0.03 U, n = 26, v 0.46 +/- 0.05 U, n = 17). Nondiabetics with PIH demonstrated higher CTT (0.53 +/- 0.03 U, n = 30) than normotensive pregnant nondiabetics (P = .002). However, diabetics with PIH and CTT activity (0.48 +/- 0.04 U) indistinguishable from normotensive pregnant diabetics (0.46 +/- 0.05 U). There were no differences in gestational age, renal function, or glycohemoglobin that could explain these observations. Therefore, we conclude that PIH in type I diabetic women, in contrast to PIH in nondiabetic pregnant women, is not associated with a further elevation in CTT. PMID- 8512665 TI - Ionic basis of hypertension in diabetes mellitus. Role of hyperglycemia. AB - Alterations of cell ion content have been reported acutely after oral glucose ingestion, and chronically in subjects with hypertension and noninsulin dependent diabetes mellitus (NIDDM). We have hypothesized that these ionic abnormalities, elevated cytosolic free calcium (Cai), and suppressed intracellular pH (pHi) and free magnesium (Mgi), common to both of these syndromes, may explain their frequent clinical coincidence. To investigate the potential role of glucose in this process, we utilized 19F- and 31P-NMR spectroscopy to measure Cai, Mgi, and pHi in normal human red blood cells before and 60, 120, and 180 min after in vitro incubation with glucose (15 mmol/L) and equimolar concentrations of the glucose analogs, L-glucose, 2-deoxyglucose, and 3-O-methylglucose. At each point in time (from t = 0 to t = 60, 120, 180 min), glucose induced significant (P < .05) elevations in Cai (27.2 +/- 2.2 to 68.3 +/- 7.2, 70.7 +/- 10.5, 59.8 +/- 10.1 nmol/L), while suppressing pHi (7.28 +/- 0.02 to 7.22 +/- 0.03, 7.23 +/- 0.03, 7.22 +/- 0.03), and Mgi (206 +/- 10 to 151 +/- 7, 131 +/- 7, 143 +/- 5 mumol/L). This glucose induced ionic effect was dose dependent, significant elevations in Cai being observed at 10 and 15 mmol/L, but not at the other concentrations tested. It was also specific, no changes in Cai being observed with any of the glucose analogs tested. Thus, hyperglycemia per se elevates Cai and suppresses Mgi and pHi in normal human red cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512668 TI - Increased concentration of endothelin messenger RNA in the mesenteric arteries of cyclosporine-induced hypertensive rats. AB - The aim of this study was to investigate the expression of endothelin-1 (ET-1) in the mesenteric arteries of cyclosporine-induced hypertensive rats. The concentration of plasma ET-1 and of mesenteric artery ET-1 messenger RNA was measured in cyclosporine-induced hypertensive and control rats. The concentration of ET-1 messenger RNA in the mesenteric arteries of cyclosporine-treated rats (25 mg/kg/day for 6 weeks) was significantly greater than in control rats (P < .05). We propose that cyclosporine-induced hypertension may be due to an increased synthesis of ET-1 in the resistant vessels. PMID- 8512669 TI - Decreased atrial natriuretic peptide receptors in the adrenal gland of genetically hypertensive rats. AB - In view of differential effects of atrial natriuretic peptide (ANP) in different models of hypertension, the present study was undertaken to assess ANP receptors in various target organs of spontaneously hypertensive rats (SHRs) and age matched normotensive Wistar-Kyoto (WKY) rats. Membranes from kidney, thoracic aorta, and adrenal gland were labeled with [125I]-iodotyrosyl rat atrial peptide (28 amino acid sequence) at 25 degrees C. Each tissue exhibited uniphasic rectangular hyperbolic saturation isotherm indicative of high affinity single species binding sites. While there were no differences in the ANP receptor densities in thoracic aorta and kidney membranes from the two groups, adrenal gland exhibited lower ANP receptors in the SHRs compared to WKY rats. This study suggests that the lower density of ANP receptors in adrenal gland may be one of the underlying contributing factors in genetic hypertension. PMID- 8512670 TI - Academic physiatry. Trends, opportunities and challenges. PMID- 8512671 TI - A quantitative study of genital skin flora in male spinal cord-injured outpatients. AB - Skin flora from the perineum, penis and urethra of 15 adult male outpatients with spinal cord injury (SCI) and neurogenic bladder dysfunction were compared with that of 10 neurologically normal controls. Gram-positive cocci and diphtheroids were the predominant isolates from controls with no enteric organisms recovered except Escherichia coli in four instances. Among SCI patients, in addition to normal Gram-positive flora, one species of Gram-negative rod was isolated from three patients, two species from five patients, three species from three patients, four species from three patients and five species from one individual. Skin isolates included various members of Enterobacteriaceae, Pseudomonas, Acinetobacter and Enterococcus. Average bacterial counts in perineal, penile and urethral cultures from SCI patients were each 1 log greater than in controls. Bacteria were isolated from 12 of 14 urine cultures obtained from SCI patients immediately after collection of skin cultures. Organisms isolated from urine were present in one or more skin sites in every instance. Differences in skin flora between SCI patients and neurologically normal persons may be the result of variables such as antibiotic usage, presence of a condom catheter, skin moisture, urine leakage, pH, skin temperature, personal hygiene and/or neurogenic bowel management. PMID- 8512673 TI - The absence of brachial plexus injury in stroke. AB - Brachial plexus injury and proximal mononeuropathy have been reported as a potential complications in the hemiplegic shoulder after a stroke. The diagnosis of brachial plexus injury and proximal mononeuropathy in the hemiplegic extremity is complicated by the upper motor neuron findings on physical examination and by the diffusely abnormal electrodiagnostic test results frequently seen in hemiplegic limbs. This study investigated the incidence of brachial plexus injury and proximal mononeuropathy after a thromboembolic stroke. Hemiplegic patients (n = 50) underwent physical examination, needle electromyography of the hemiplegic extremities and nerve conduction studies across the brachial plexus within 4 months after a stroke. Combining the physical examination and electromyographic findings we were unable to make a diagnosis of brachial plexus injury or proximal mononeuropathy in any hemiplegic patient. Spontaneous electromyographic activity was observed in 68% of the arms and 70% of the legs examined on the hemiplegic side. The severity and incidence of spontaneous activity was evenly distributed in upper and lower trunk muscles. Mean central latencies across the lower brachial plexus were slightly delayed (12.5 +/- 2 v 11.6 +/- 2.2 ms, P < 0.01) compared with the contralateral normal limb, but in no case was the F wave unilaterally unelicitable. The mean hypothenar compound muscle action potential amplitude was diminished (7 +/- 2.7 v 9.2 +/- 4.1 mV, P < 0.01) in the hemiplegic hand compared with the normal side and the degree of amplitude loss inversely corresponded (r = -0.6, P < 0.01) to the amount of spontaneous electromyographic activity observed in the first dorsal interosseus muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512672 TI - Screening for urinary tract infection in children with neurogenic bladders. AB - Urinary tract infections (UTIs) are a frequent and potentially disabling problem for children with neurogenic bladders. Frequent monitoring for UTIs using bacterial culture is expensive and troublesome; thus an inexpensive, dependable screening method is desirable. Three hundred and twenty-nine urine specimens were obtained from 141 children with neurogenic bladders, 86% of whom had meningomyelocele. During the 11-month study period, 43% of the children had at least one positive culture (> or = 100,000 CFU/ml). The results of bacterial culture were compared with the occurrence of signs and symptoms, the presence of reflux and the results of a dipstick test for nitrite and leukocyte esterase. Analysis of the data revealed that (1) UTIs were significantly more common in children with reflux; (2) the presence of signs and symptoms was neither sensitive nor specific (positive predictive value (PPV) = 0.44, negative predictive value (NPV) = 0.84); (3) urinalysis was an unreliable screening tool (PPV = 0.63, NPV = 0.73); and (4) the combination of nitrite and leukocyte esterase was more sensitive and specific than either by itself (combined PPV = 0.69, NPV = 0.88). Children with neurogenic bladders who have reflux or have signs and symptoms should continue regular bacterial cultures, whereas others can be screened dependably using the combined leukocyte esterase and nitrite test. PMID- 8512674 TI - Inter- and intra-rater reliability of the pressure threshold meter in measurement of myofascial trigger point sensitivity. AB - This study was designed to establish the intra-rater and inter-rater reliability of measurements of trigger point sensitivity using a commercially available pressure threshold meter. Fifty healthy adult volunteers (25 men and 25 women, aged 20 to 51 years) underwent repeated pressure threshold readings from two separate trigger point locations in the trapezius muscle, TP2 (left) and TP3 (right) by two independent examiners. Pressure threshold readings, using a 1.0 kg/s application, were done alternately by each experimenter. Measurements from each trigger point were completed 5 minutes apart. Intraclass correlation coefficients (ICC) revealed the inter-rater reliability to be high for both the first (ICC = 0.82) and second trial (ICC = 0.90) of TP2 and for the first (ICC = 0.86) and second trial (ICC = 0.92) of TP3. Intra-rater reliabilities for TP3 (ICC = 0.91) were higher than for TP2 (ICC1 = 0.80; (ICC2 = 0.83). These results show that the pressure threshold meter is highly reliable in measuring trigger point sensitivity, between and within experimenters, and may be useful in the diagnosis and monitoring of treatment of myofascial pain syndrome. PMID- 8512675 TI - Cardiac precautions for non-acute inpatient settings. AB - Activity progression of persons with physical disabilities and accompanying cardiovascular disease in medical rehabilitation centers is traditionally based on cardiac precautions derived from acute care settings. Concern that these guidelines were too conservative and restrictive led to exercise testing and evaluation of 64 physically disabled male patients with a history of coronary artery disease. The sample had a mean age of 62.4 years. The exercise test was an adaptation of the Schwade Arm Ergometer Protocol with blood pressure measured at baseline, immediately after each 2 minutes of exercise, peak exercise and each minute for 6 minutes after peak exercise. Heart rate was monitored continuously. Patients achieved a mean peak heart rate of 115 beats per minute, mean peak systolic pressure of 169 mm Hg and mean peak diastolic pressure of 89 mm Hg. Ischemic electrocardiographic changes occurred in four of the 64 patients. Based on the achieved ranges of values of heart rate, systolic and diastolic pressures and comparison of these results with baseline (pre-exercise) values, more liberal guidelines for prescribing activity in the non-acute inpatient setting are provided. PMID- 8512676 TI - Intercostal somatosensory-evoked potentials. A new technique. AB - Presently, there are few electrodiagnostic medicine techniques to evaluate lesions affecting the thoracic nerve roots or spinal cord. A new electrophysiologic technique to assess these structures, intercostal somatosensory-evoked potentials (SEPs), is described. Thirty neurologically normal subjects were used in this investigation to generate intercostal SEPs. Bilateral intercostal SEPs were easily elicited after stimulation of the third intercostal nerves just lateral to the sternum anteriorly. Intercostal SEPs were also easily elicited from the fifth, seventh and ninth intercostal nerves along the anterior axillary line bilaterally. Intercostal SEPs are not only easily and painlessly obtained, but are specific for individual spinal levels. This SEP method will provide the clinician with another neural stimulation procedure to assist in the diagnosis of both central and peripheral thoracic neural compromise. PMID- 8512677 TI - Catastrophic reaction after stroke. A case study. AB - The catastrophic reaction is a rare affective disorder following left hemispheric strokes. It is characterized by a disruptive emotional outburst involving anxiety, agitation and aggressive behavior. A case is presented that appears to underscore the intense frustration that these individuals experience when they cannot adequately express themselves through language. The catastrophic reaction behavior proved to be unremitting and failed to respond to withdrawal of the patient from threatening or difficult therapies, use of medications or attempts at behavioral modification. The catastrophic reaction appears to be a specific consequence of the intense frustration and perceived loss associated with an expressive aphasia. This may help explain the reportedly higher incidence of depression in left frontal strokes. PMID- 8512678 TI - Effect of transdermal clonidine on spinal spasticity. A case series. AB - Clonidine, a centrally acting alpha 2 receptor adrenergic agonist, has been successfully used as adjunctive therapy in patients with spinal cord injury with problematic spasticity not adequately controlled by recognized spasmolytic agents. A transdermal system providing approximately constant and continuous systemic delivery of clonidine has been recently introduced to enhance patient compliance. However, experience with transdermal clonidine in the management of spasticity is limited. Three cases are presented of patients with spasticity as the result of cervical spinal cord injury, inadequately managed by oral baclofen, in whom transdermal clonidine was administered. Significant improvement in spastic hypertonia was observed in all three cases. Transdermally delivered clonidine was well tolerated, with reported side effects limited to dryness of the mouth. PMID- 8512679 TI - Transverse myelitis complicating systemic lupus erythematosus: treatment including hydroxychloroquine. Case report. AB - Transverse myelitis has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE). A review of the literature reveals only 10 cases of transverse myelitis as the initial presentation of SLE, and only one with reported benefits from antimalarial therapy. The case of a 30-year-old woman is reviewed. She presented to the emergency room with complaints of hypogastric and low back pain. The ensuing course was one of frank urinary retention and rapidly progressing quadriparesis. Magnetic resonance imaging of the spine revealed marked edema of the cervical and thoracic spine. A diagnosis of SLE was based on positive antinuclear antibodies and leukopenia. The patient was treated with high dose methylprednisolone, plasmapheresis and pulse cyclophosphamide for 3 months. Subsequently, treatment was begun with hydroxychloroquine, and significant improvement in her neurologic and functional status was achieved after 1 month of therapy. Ten months after her onset of symptoms, the patient suffered an acute exacerbation of paraparesis and urinary retention. Again, she improved clinically after high dose methylprednisolone and pulse cyclophosphamide for 1 month. Hydroxychloroquine was continued throughout the duration of therapy. PMID- 8512680 TI - Continuous passive motion in the rehabilitation setting. A retrospective study. AB - Continuous passive motion (CPM) has been commonly used in the postoperative rehabilitation of patients after total knee arthroplasty. In the acute care hospital, most studies have found CPM to be useful in improving range of motion and reducing length of stay. The benefit of CPM in the rehabilitation hospital has not been studied. The charts of 61 patients who had undergone total knee arthroplasty and subsequently were admitted to the East facility of the Kessler Institute for Rehabilitation were reviewed. Patients were separated into two groups: Group 1 received CPM for 3 to 4 hours/day and physical therapy for 2 hours/day. Group 2 received only physical therapy. There was no significant difference in passive range of motion or length of stay between Group 1 and Group 2. An analysis of the 16 patients who underwent bilateral replacement was undertaken. Patients in Group 1 (n = 7) achieved an average increase in passive range of motion of 20.1 degrees, whereas those in Group 2 (n = 9) achieved an increase of 12.7 degrees (P = 0.18). Power analysis demonstrated the need for 50 patients per subgroup to achieve significance. The lack of statistical significance in this subgroup may be a reflection of the small study population (n = 16). The following conclusions can be drawn concerning the use of CPM in the rehabilitation setting: (1) CPM was of no added benefit to those patients admitted after single knee replacement, and (2) CPM may be beneficial to those patients admitted after bilateral knee replacement. PMID- 8512681 TI - Severe burns resulting from magnetic resonance imaging with cardiopulmonary monitoring. Risks and relevant safety precautions. AB - Cardiopulmonary monitoring may be desirable during magnetic resonance imaging (MRI) of hemodynamically unstable patients, but must be performed with great caution. This case report describes a severe burn associated with pulse oximetry use during MRI scanning. Risk of this injury is greatest in infants and in individuals with obtundation, general anesthesia, insensate limbs or impairments of verbal communication. Several safety precautions are described. Preparation and monitoring of patients undergoing MRI scanning with cardiopulmonary monitoring should be performed only by specially trained personnel. PMID- 8512682 TI - Discussing cardiopulmonary resuscitation with elderly rehabilitation patients. Ethical and clinical considerations toward the formation of policy. AB - Studies have demonstrated that most elderly persons who undergo cardiopulmonary resuscitation do not survive to hospital discharge. Because resuscitation efforts among elderly patients may fail either to restore hemodynamic stability or the patient's prearrest functional levels, ethical arguments as well as regulatory standards have urged the involvement of patients and their families in deciding about the advisedness of cardiopulmonary resuscitation. This article examines various ethical dimensions of conducting do-not-resuscitate discussions with competent, elderly persons in acute rehabilitation environments. Viewpoints that seek to excuse or resist do not resuscitate discussions among elderly rehabilitation consumers will be discussed as well as programmatic or psychological factors that appear to bolster such positions. These arguments, however, will be shown to be inferior to others that urge rehabilitation providers to engage their patients in frank and sincere discussions regarding their resuscitation status in the event of arrest. PMID- 8512683 TI - A scientific rationale for protective therapy in Parkinson's disease. AB - The desire to introduce neuroprotective therapy for Parkinson's disease has begun to focus attention on pathogenetic mechanisms responsible for cell death. Considerable theory and some evidence have now accumulated to suggest that factors related to oxidative stress, mitochondrial bioenergetic defects, excitatory neurotoxicity, calcium cytotoxicity, and trophic factor deficiencies acting either singularly or in combination may contribute to the development of cell death in Parkinson's disease. A better understanding of the specific pathogenetic mechanism involved in cell degeneration might provide a scientific basis for testing a putative neuroprotective therapy. This chapter reviews the theory and evidence in support of these different mechanisms and possible strategies that might provide neuroprotection and interfere with the natural progression of Parkinson's disease. PMID- 8512684 TI - Optimizing the recovery of chemically reduced monoclonal antibody for site specific technetium-99m radiolabeling. PMID- 8512685 TI - An efficient method for identifying an integrated cosmid in Aspergillus parasiticus. PMID- 8512686 TI - An efficient procedure for multiple transformations of yeast in parallel. PMID- 8512687 TI - Rapid small-scale isolation of mRNA from whole yeast cells. PMID- 8512688 TI - A simple improvement to the Triton lysis procedure for plasmid isolation. PMID- 8512689 TI - An improved procedure for direct phenol extraction of single-stranded M13 DNA for sequencing. PMID- 8512690 TI - Use of polyethylene glycol for purification of DNA from leaf tissue of woody plants. PMID- 8512691 TI - An improved method for preparing lambda ZAP II DNA. PMID- 8512692 TI - Rescue of plasmid DNA from nonviable bacterial glycerol stocks. PMID- 8512693 TI - Modified colony hybridization using Whatman 54 filter paper. PMID- 8512695 TI - A strategy for maximizing time efficiency in protocols requiring multiple centrifugation steps. PMID- 8512694 TI - A rapid CTAB DNA isolation technique useful for RAPD fingerprinting and other PCR applications. PMID- 8512696 TI - A simple method for the reuse of polystyrene cell culture flasks. PMID- 8512697 TI - Luminescent reporter gene assays for luciferase and beta-galactosidase using a liquid scintillation counter. PMID- 8512698 TI - Fluorstamp. PMID- 8512699 TI - A multiplex polymerase chain reaction colony miniprep. PMID- 8512700 TI - A method of cloning multiple direct repeats of a DNA segment. PMID- 8512701 TI - A rapid procedure for screening fibroblast packaging cell lines for secretion of selectable retrovirus. AB - A simple method is described for rapidly screening fibroblast packaging cell line clones for high-titer secretion of retroviruses carrying a selectable marker. Virus-containing supernatants are used to infect FDC-P1 myeloid cells in 24-well tissue culture plates, selection is applied and wells containing live cells (infected by retrovirus and thus expressing the selectable marker) are detected after 5 to 10 days. The number of live cells in each well is proportional to the retroviral titer of the infecting supernatant. The assay is quick to set up and allows simultaneous screening of many samples. PMID- 8512702 TI - Detection of antibodies to the HIV-1 p25/24 and gp120 proteins by sphere-linked immunodiagnostic assay (SLIDA). AB - In this paper, we have used the technique known as sphere-linked immunodiagnostic assay (SLIDA) for the detection of antibodies to HIV-1 p25/24 and gp120 proteins. In this technique, the p25/24 and gp120 proteins were covalently bonded to 0.5 micron carboxylated microspheres. They were then exposed to serial dilutions of rabbit antiserum to HIV-1 p25/24, sheep antiserum to gp120 and dilutions of the corresponding normal sera. Specific immunolabeling was monitored by using gold labeled secondary antibody. The gold particles bound to the microspheres were an indication for the presence of specific antibody in the serum sample. The gold labeled microspheres were photographed using a transmission electron microscope, and the number of gold particles bound to the microspheres were counted manually using the electron micrographs. The specificity and sensitivity of the technique were then compared to enzyme-linked immunosorbent assay (ELISA) and Western blotting. PMID- 8512703 TI - A rapid and simple method for determining the DNA sequences of fragments inserted into vaccinia virus. AB - Recombinant virus vectors such as vaccinia virus, adenovirus and herpesvirus are frequently used to express a variety of foreign products. A rapid method allowing the precise identification of recombinants would be useful to confirm the nature of a newly produced recombinant and, in particular, to discriminate between recombinants bearing near-identical foreign products. Using vaccinia virus, we describe a method that in one day provides sequence analysis of the recombinant viral DNA. PMID- 8512704 TI - Direct cycle sequencing of mutated alleles detected by PCR single-strand conformation polymorphism analysis. AB - A rapid protocol for direct sequencing of a mutated allele, detected by combining polymerase chain reaction with single-strand conformation polymorphism (PCR-SSCP) analysis and cycle sequencing using a thermal cycler, is described. End-labeled radioactive primers were used both for PCR-SSCP analysis for the detection of p53 gene mutation and for cycle sequencing using delta Taq Version 2.0 DNA Polymerase. The point mutations along the various exons of the p53 gene can be rapidly determined by this sequencing method. This protocol requires only a small amount of DNA template (0.1 microgram) and produces sequencing images with low backgrounds and very uniform band intensity. It has also been used successfully in the study of other gene mutations including ras and NF-1 (neurofibromatosis 1) genes. PMID- 8512705 TI - A simple and rapid method for purification of oligodeoxyribonucleoside methylphosphonates. AB - An alternative dimethoxytrityl-on (dmt-on) method is described to purify hydrophobic oligodeoxyribonucleoside methyl-phosphonates (OM) with a phosphodiester linkage at the 5' end, instead of the conventional dmt-off method using a DEAE ion-exchange column. This method is modified from the reverse-phase method for purification of normal oligonucleotides. PMID- 8512706 TI - A baculovirus-expressed fusion protein containing the antibody-binding domain of protein A and insect luciferase. AB - A fusion construct encoding two antibody-binding sites of protein A from Staphylococcus aureus and click beetle, Pyrophorus plagiophthalamus, luciferase (LucGR) was designed and expressed using the baculovirus system. The construct was inserted under the transcriptional regulation of the polyhedrin gene promoter of the Autographa californica nuclear polyhedrosis virus (AcNPV) and expressed in the insect Spodoperta frugiperda cell line during viral infection. The properties of the resultant chimeric protein product, protA-LucGR, were studied both in vivo and in vitro by using i) luminometry, ii) immunoblot analysis, iii) immunoprecipitation, iv) metabolic labeling procedures and v) luminescent immunoassays. Together, the results clearly demonstrate that the light-emitting properties of the fused luciferase construct remain intact. Further, the antibody binding domain of protein A retains its activity as it binds to both rabbit and goat as well as human immunoglobulins. Due to the dual biological function of this fusion protein, it should provide a potential reagent within the field of molecular biology and diagnostics. PMID- 8512707 TI - A method for producing recombinant baculovirus expression vectors at high frequency. AB - A system has been developed that can generate recombinant baculovirus expression vectors at frequencies approaching 100%. This system provides a selection for recombinant viruses by using the essential gene downstream of the Autographa californica nuclear polyhedrosis virus (AcMNPV) polyhedrin expression locus. Two AcMNPV derivatives were constructed in which the expression locus and part of the downstream gene are flanked by restriction sites. The parental viruses are viable; however, restriction of the viral DNAs removes an essential piece of the viral genome. Transfer vectors carry a copy of the missing sequences downstream from the site into which foreign genes are inserted for expression; hence, recombination between a transfer vector and the restricted viral DNA can restore the integrity of the essential gene. Such recombination events also transfer any foreign gene present in the expression locus of the transfer vector to the viral genome. Recombinant viruses therefore have a selective advantage over nonrecombinant viral DNAs. Consequently, a high proportion of the viruses obtained by co-transfecting transfer vector DNA and restricted viral DNA of one of these new viruses expresses the target gene from the transfer vector. This system greatly reduces the time needed to make recombinant baculovirus expression vectors. PMID- 8512708 TI - Recombinant retroviruses containing novel reporter genes. AB - Two histochemical marker genes, Drosophila alcohol dehydrogenase (ADH) and human placental alkaline phosphatase (ALP), were cloned into the recombinant retroviral vectors pLJ and pgag beta-actin. The resulting vectors were transfected into retroviral producer cell lines, psi CRE and psi CRIP, and stable recombinant retrovirus producers were isolated. Recombinant virus was harvested and used to transduce genes into several cell lines, singly or in conjunction with lacZ (Escherichia coli beta-galactosidase)-containing retrovirus. Cell lines were then stained using standard histochemical methods for recombinant gene expression. We found that multiple gene products could be identified in the same cell populations and in the case of ALP and beta-galactosidase, in the same cells. The resulting reagents should be useful for a variety of cell-marking studies including those involving multiple clonal analysis and developmental studies for gene therapy. PMID- 8512709 TI - Direct sequencing of double-stranded PCR products incorporating a chemiluminescent detection procedure. AB - A simple and reliable method is described for direct sequencing of material generated by the polymerase chain reaction (PCR). Sequencing reactions can be performed directly on PCR products without the need for purification of the template by removal of residual deoxyribonucleoside triphosphates or primers. The coupling of a chemiluminescent detection system with the use of the same primers in the initial and sequencing PCR's allows for sequencing of a number of PCR products on the one gel. PMID- 8512710 TI - 3' transcript mapping of the Chlamydomonas reinhardtii chloroplast psbK mRNA using a novel method to prepare 3' end-labeled single-stranded DNA probes. AB - We have developed a novel method for the rapid preparation of large quantities of 3' end-labeled single-stranded (ss) DNA (ssDNA) probes for transcript mapping. A recombinant phagemid vector containing the probe sequence was used to raise large quantities of ssDNA. Based on the DNA sequence of the probe, an oligonucleotide primer complementary to the ssDNA probe was synthesized. Annealing of the primer to the purified ssDNA phagemid clone produced a short double-stranded DNA duplex containing a restriction site, which was then cut with a restriction enzyme to generate a 5' overhang of the primer strand. The phagemid DNA was labeled at the 3' end with the Klenow fragment of polymerase I. The low melting temperatures of the short primer-phagemid duplex caused the primer to dissociate during the hybridization of the probe to algal RNA. For this reason, the probe can be used for S1 mapping without further purification. This method was used to map the 3' end of the Chlamydomonas reinhardtii chloroplast psbK transcript. PMID- 8512711 TI - Trityl monitoring of automated DNA synthesizer operation by conductivity: a new method of real-time analysis. AB - AutoAnalysis is a new method for detecting and quantitating the trityl cation released each cycle on automated DNA synthesizers. The trityl (dimethoxytrityl) cation is removed from the growing oligonucleotide after each base addition and is a useful measure of synthesis efficiency. The traditional absorbance method of collecting each trityl effluent with a fraction collector, followed by dilution with an acid solution and careful quantitation by UV/VIS spectroscopy is costly, tedious and prone to error. The absorbance method for trityl cation analysis must usually wait until the synthesis is complete. Interruption of a failed operation, for a variety of reasons, such as an empty reagent reservoir, is thus not possible. Taking advantage of the conductive properties of the trityl cation, immediate and real-time quantitation is now possible by integrating the total conductance of the flowing stream during the detritylation step after each nucleoside addition in DNA synthesis. A conductivity cell is mounted downstream, past the synthesis column. The conductivity signal is processed and displayed as the current average stepwise yield and overall yield. If the yield drops below a pre-set threshold value because of a failure situation, the synthesizer will interrupt, preserving reagents. AutoAnalysis allows trityl monitoring with complete automation on the Applied Biosystems Models 392 and 394 DNA/RNA Synthesizers. PMID- 8512712 TI - [Meaning of mosaic color area in mitral regurgitation. Echocardiographic transesophageal study]. AB - OBJECTIVE: The purpose of our study was to analyse the meaning of total and mosaic color Doppler area of the mitral regurgitation jet, in terms of the degree of mitral regurgitation severity. PATIENTS: In and out patients referred to the Echocardiographic Laboratory of Gregorio Maranon General Hospital, Madrid. SETTING: Transesophageal echocardiographic prospective study MATERIAL AND METHODS: By pulsed and color Doppler transesophageal approach we studied 94 consecutive patients with mitral regurgitation diagnosis. We divided the entire population in three groups according to the degree of transthoracic mitral regurgitation severity and mitral regurgitation color area index (Groups I, II and III). In each patient we systematically measured the regurgitant maximal area (AT) and of the aliasing color area, as well as maximal peak velocity (VIS) and area (AIS) of the reversed pulmonary venous pulsed Doppler flow obtained at the level of the left upper pulmonary vein. RESULTS: For the group I, color Doppler AT was 411 +/- 315 mm2 and AN was 204 +/- 123 mm2 (R = 0.25), pulmonary venous pulsed Doppler VIS was 4 +/- 8 cm/sec (R = NS for AT and 0.79 for AN) and AIS was 9 +/- 6 mm2 (R = NS for AT and 0.82 for AN). In the group II, color Doppler AT was 802 +/- 447 mm2, AN was 671 +/- 307 mm2 (R = 0.42). the pulmonary venous pulsed Doppler VIS was 22 +/- 12 cm/sec (R = NS for AT and 0.66 for AN). In the group III we obtained an AT value of 1174 +/- 462 mm2 and an AN value of 1092 +/- 417 mm2 (R = 0.62). In this group the pulmonary venous pulsed Doppler VIS was 50 +/- 13 cm/sec (R = 0.57 for AT and 0.76 for AN) and the correspondent AIS was 671 +/- 570 mm2 (R = 0.38 for AT and 0.91 for AN). CONCLUSIONS: Mosaic transesophageal echocardiographic color Doppler area of mitral regurgitant jets has a direct relationship with the reversal criteria of pulsed Doppler pulmonary venous flow. This relationship is greater than the total color Doppler area of the same regurgitant jet. The mosaic color Doppler area of mitral regurgitant jets is a more correct estimation of the systolic variation of left atrial pressure, when compared with the total color area of mitral regurgitation. PMID- 8512713 TI - Effects of diltiazem on myocardial ischemia in patients with coronary artery disease. AB - OBJECTIVES: To evaluate the effect of diltiazem on the characteristics of ischemic episodes detected by Holter monitoring in a group of patients with proven coronary artery disease. SETTING: Department of Cardiology, Santa Marta Hospital, Lisbon. METHODS: Eleven selected out-patients, aged 48 to 79 years, with transient ST-segmental depression on Holter monitoring and proven coronary artery disease, were submitted to a double-blind crossover placebo controlled study, during hospitalization. The total ischemic burden of each patient and an analysis of ischemic episodes were evaluated before and during the drug/placebo phase trial. Three groups of ischemic episodes were considered: group I constituted by 66 episodes found on basal Holter recording; group II by 28 episodes detected during placebo trial and group III by 12 episodes detected during diltiazem trial. RESULTS: A reduction of the number of ischemic episodes was predominantly observed with the diltiazem administration. Statistically significant differences were observed between basal and placebo groups and especially between basal and diltiazem groups concerning the mean maximum ST segment depression (2.17 vs 1.80; p = 0.030 and 2.17 vs 1.54; p = 0.0091). Significant differences were also obtained between the above mentioned groups concerning the heart rate variation from the onset of ST-segment depression to its maximum depression (13.5 vs 9.69; p = 0.023 and 13.5 vs 2.91; p = 0.01) and from two minutes before the onset of ST-segment depression to its maximum depression (21.2 vs 12.67; p = 0.012 and 21.2 vs 8.75 p = 0.016). CONCLUSIONS: Diltiazem seems to reduce the number of ischemic episodes in patients with coronary artery disease, during hospitalization. The study of its effects on the characteristics of ischemia requires further investigation with a greater number of patients. The limitations of the present study, described in the discussion, must be taken into account in future pharmacological investigations with Holter monitoring. PMID- 8512714 TI - [Transesophageal echocardiography. Analysis of 15 months of activities]. AB - At the Centre of Thoracic Surgery we have so far performed 235 exams of transesophageal echocardiography (TEE). The aim of our study was critical analysis of the exams and if possible the comparison of the information given by TEE, transthoracic echocardiography (TTE) and surgery. We used biplane 5 MHz probe. The indications of the exams were: prosthetic mitral valve (58), peripheral embolization (40), clinical suspicion of infective endocarditis (32), aortic dissection (20), atrial septal defects (17), quantification of mitral insufficiency in native valve (15) and others. TEE showed prosthetic disfunction in 20 patients, spontaneous echo contrast in 17 of 40 patients and vegetations in 14. TTE identified 4 false atrial defects. TEE maintained mitral regurgitation quantification in 4 patients and changed in 9. So, TEE is important to detect most cardiac diseases. PMID- 8512715 TI - [Long-term results of mitral valve prosthesis in patients with severe anatomo functional involvement of the left ventricle]. AB - The purpose of this paper was to study the long term results (3.6 +/- 1.4 years) of 74 patients with severe mitral regurgitation (MR), with cardiomegaly and functional class (FC) III and IV, who underwent mitral valve replacement with biologic and mechanical prostheses. Seventy four patients were submitted to mitral valve replacement for treatment of severe MR. Their mean age were 43 years, 63.5% were male and 70.3% belonged to white race. The biologic prostheses were used in 71.6% of the patients. The clinical symptoms were evaluated by the New York Heart Association FC. The cardiac enlargement was evaluated by cardiothoracic ratio and the left ventricular function by echocardiogram. All patients with mechanical prostheses and with atrial fibrillation received long term anticoagulant therapy. Before the surgery all patients received digitalis, diuretics and vasodilators. Before the surgery 66.2% of the patients were in FC III and 33.8% in FC IV; 3.6 +/- 1.4 years after the surgery 62.1% were in FC I, 27% in FC II and 10.8% in FC III. The cardiothoracic ratio decreased from 61.8 +/ 5.7% to 55.7% (p < 0.05); the diastolic diameter of the left ventricle decreased from 6.1 +/- 0.64 to 5 +/- 0.89 (p < 0.05) and the ejection fraction didn't change significantly (p > 0.05). Thromboembolism occurred in 2.7% of the patients. The mitral valve replacement produces a very good later results, relief the symptoms of the patients with severe mitral regurgitation, decrease the cardiac size and improve the left ventricular function. PMID- 8512716 TI - [Assessment of pulmonary arterial pressure in adults with Doppler echocardiography]. AB - PURPOSE: To assess the role of pulsed Doppler echocardiography (PDE) in the indirect assessment of pulmonary artery (PA) pressure (P), analysing the pulmonary velocity blood flow curves (PVBFC) profile. PATIENTS AND METHODS: Sixty one adults with several kinds of heart disease were submitted to heart catheterization to obtain PAP (systolic, diastolic, mean), and other hemodynamic variables. A PDE examination was performed in all to obtain the PVBFC at the level of the pulmonic annulus. Qualitative features of the curve were analysed (morphological pattern, presence of pulmonic regurgitation) as well as quantitative data (acceleration time = AT, right ventricle ejection time = RVET index, AT/RVET index AT corrected for heart rate = ATC), which were compared to the invasive measurements. RESULTS: An abnormal rapid acceleration of the PVBFC, with triangular configuration, was noted in patient with pulmonary hypertension (PH), in contrast to the dome-like shape of the PVBFC in normal PAP. Pulmonary regurgitation was more frequent (p < 0.05) in patients with severe PH (mean PAP > or = 40 mmHg), comparing with patients with PAP < 40 mmHg. Inverse linear correlations were observed between AT and mean PAP, particularly when sinus rhythm was present (r = 0.89; p < 0.05) excluding patients with atrial fibrillation (19 cases). CONCLUSION: PDE is an useful and noninvasive method for indirect evaluation of PAP in adults, especially during stable sinus rhythm, in heart rate range from 60 to 115 bpm. PMID- 8512717 TI - [Successful operation of aortic abscess ruptured into left atrium. Diagnostic importance of color coded Doppler echocardiography]. AB - Myocardial abscesses are a serious complication of infectious endocarditis. A 60 years old male patient with subaortic ring abscess is reported. A fistula developed between the left ventricular outflow tract and the left atrium. Doppler echocardiography was of outmost importance for diagnosis. Surgery was successfully performed. PMID- 8512718 TI - [Cardiac changes in a case of mitochondrial encephalomyopathy]. AB - In the present article the authors describe a case of a twenty-one year-old patient with a mitochondrial encephalomyopathy presenting cardiac changes. Mitochondrial encephalomyopathy a multisystemic disease is described in various publications having cardiac involvement although there are sparse references about cardiomyopathy in this same disease. In the present case, the patient had a syndrome of both Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes (MELAS) and Myoclonic Epilepsy and Ragged Red Fibers (MERRF). There were no significant changes in the cardiac conductivity studied by ECG but an echocardiographic pattern of hypertrophic cardiomyopathy was found. PMID- 8512719 TI - [Rupture of the interventricular septum and the left ventricular wall caused by non-penetrating thoracic trauma. Report of a case]. AB - Heart contusion is one of the many lesions that can result from closed chest trauma. The fatal case of a seven years old boy is presented. A ventricular septum and left ventricle free wall rupture resulted from a backward kick of a cow. Diagnosis, although too late, was made by echo-Doppler cardiography. This examination should be made whenever there is a closed chest trauma. PMID- 8512720 TI - [Ambulatory determination of arterial pressure. "Current and future perspectives"]. PMID- 8512721 TI - [Ambulatory determination of arterial pressure. Methods, results, and their validation]. PMID- 8512722 TI - [Diagnostic hints of ambulatory monitoring of arterial pressure]. PMID- 8512723 TI - [Decision to treat, treatment control, and clinical trials]. PMID- 8512724 TI - [Blood pressure ambulatory monitoring: future perspectives]. PMID- 8512725 TI - [Coronary artery ectasia: clinical and angiographic characteristics and prognosis]. AB - OBJECTIVE: To evaluate the incidence of coronary ectasia and its distribution by coronary vessels, natural history and follow-up in coronary artery disease patients. DESIGN: Retrospective study from 1982 to 1985. SETTING: Hemodynamics Cardiology Department of a Central Hospital. PATIENTS: In 1100 patients with coronary artery disease, there were 40 patients, 39 men and 1 woman, with mean age of 53.98 +/- 7.49 years. MATERIAL AND METHODS: Coronary ectasia was defined by CASS criteria as: Diameter of a vessel in the coronarography up to one and half times the diameter of a adjacent normal branch. In the clinical profile, both risk factors and clinical parameters such as angina or myocardial infarction were evaluated. The distribution of coronary ectasia by segments and vessels was also noted. In follow-up we analysed major cardiac events, as well as the need for by-pass surgery. RESULTS: The incidence of coronary ectasia was 3.6%. Smoking was the most frequent risk factor. 42.5% of patients had anti-ischemic therapy and 87.5% has previous angina, 62.5% of whom had myocardial infarction. Angiographic findings showed only one ectatic coronary artery in 25 patients. Right coronary artery was the most frequent ectatic vessel (75%), and there was a higher prevalence of coronary ectasia in the proximal segments (p < 0.001). 33 patients had stenotic lesions associated to coronary ectasia. At a mean follow-up of 63.15 +/- 30.46 months, there were nine major cardiac events (one death, three myocardial infarctions and five new episodes of unstable angina), and eighteen patients underwent coronary by-pass surgery. There were no differences between "pure" ectatic and stenotic coronary associated groups, even in patients who needed bypass surgery. CONCLUSIONS: These results confirmed the usual incidence of coronary ectasia, as well as the predominance of right coronary artery ectasia. Proximal segments were more frequently ectatic. Although "pure" coronary ectasia can be implicated in angina or myocardial infarction, we think that a worse prognosis depends on the association of stenotic coronary artery disease. PMID- 8512726 TI - [Use of spreadsheet for statistical and graphical processing of records from the ambulatory blood pressure monitor Spacelabs 90207]. AB - The introduction of portable devices for non-invasive ambulatory blood-pressure measurement is recognized as an advance in the study of human arterial hypertension, allowing a significant improvement in the selection of hypertensive patients as well as in the analysis of the effects of antihypertensive drugs during clinical trials. The Spacelabs 90207 is a recent example of this kind of apparatus, possessing high levels of portability and being highly classified in validation studies. Nevertheless, the software of this apparatus (like other similar devices) has severe limitations in what concerns the calculation of the area under the curve of blood pressure during the time of measurement, as well as in the possibility of grouping several records in a database for easy statistic and graphic analysis of different groups of records. In order to overcome these difficulties, the authors describe the development of a group of programs, using Microsoft Excel v3.0 spreadsheets and macros, that allow a direct import of individual files from the Spacelabs software to a spreadsheet and its further processing in three phases. These three phases, which we designated by "conversion", "export to database" and "statistic and graphic analysis", will permit an easy and fast statistic and graphic analysis of selected groups of records. PMID- 8512727 TI - [Transesophageal echocardiography study with dynamic spontaneous contrast of the left atrial appendage, its relationship with the anatomy and thrombus formation]. AB - OBJECTIVE: Transesophageal two-dimensional echocardiographic study of anatomical characteristics of the left atrial appendage and its relation to spontaneous dynamic echocardiographic contrast. DESIGN: Outpatients undergoing a prospective two-dimensional transesophageal echocardiographic study. SETTING: Consecutive outpatients studied at the Echocardiographic Laboratory of Gregorio Maranon General Hospital, Madrid. MATERIAL AND METHODS: In each patient at the level of the left atrial appendage we calculated the following transesophageal echocardiographic parameters: end-systolic and end-diastolic maximal longitudinal and transversal diameters, total systolic and diastolic areas, percentage of systolic fractional shortening, presence of left atrial appendage thrombus and spontaneous dynamic echo-contrast. MAIN RESULTS: Left atrial appendage spontaneous dynamic contrast was observed in 48% of the total population. In the group of patients with left atrial spontaneous echo-contrast we observed larger longitudinal systolic (44 +/- 14 mm vs 28 +/- 13 mm, p = 0.01) and diastolic (52 +/- 16 mm vs 38 +/- 12 mm, p = 0.005) diameters, larger transversal systolic (25 +/- 10 mm vs 19 +/- 6 mm, p = 0.03) and diastolic (28 +/- 8 mm vs 25 +/- 9 mm, p = NS) diameters and also larger systolic (601 +/- 204 mm2 vs 337 +/- 110 mm2, p < 0.0001) and diastolic (715 +/- 230 mm2 vs 507 +/- 184 mm2, p = 0.001) areas, compared to the group without this dynamic echocardiographic phenomena. Left atrial appendage percentage of fractional shortening was considerably reduced in patients with spontaneous dynamic echo-contrast (15 +/- 14% vs 39 +/- 18%, p = 0.001) and related to local thrombus formation (13% vs 1%, p < 0.001). CONCLUSIONS: Left atrial spontaneous dynamic echo-contrast is more common in patients with enlarged left atrial appendage systo-diastolic diameters and areas. In this group of patients the presence of left atrial spontaneous echo-contrast is related to a significant reduction in left atrial appendage contractile function and thrombus formation. Parameter analysis of left atrial appendage anatomy by two-dimensional transesophageal echocardiography may have clinical relevance in the assessment of patients with high risk for left atria thromboembolic phenomena. PMID- 8512728 TI - Clinical and electrophysiologic characteristics in patients with Wolff-Parkinson White pattern. AB - OBJECTIVES: (1) To obtain a relation between clinical and electrophysiologic characteristics in patients with Wolff-Parkinson-White pattern. To evaluate the atrial vulnerability for inducing atrial fibrillation and its relation to the electrophysiologic protocol phase. (3) To study the effects of flecainide on the treatment of induced sustained supraventricular arrhythmias. SETTING: Department of Cardiology at Santa Marta Hospital. METHODS: An electrophysiologic testing was performed in twenty-three consecutive patients aged from 14 to 55 years, with Wolff-Parkinson-White (WPW) pattern on ECG. Two groups of patients were considered: group I with 12 asymptomatic or nearly asymptomatic patients; group II with 11 symptomatic patients. The parameters studied were the anterograde effective refractory period of the accessory pathway, the number of patients with different types of supraventricular tachycardias (SVT), the relation between the stimulation protocol phase (scanning/DDT/burst) and the occurrence of atrial fibrillation, and the effects of the flecainide on the treatment of induced sustained supraventricular arrhythmias. RESULTS: Statistically significant differences were obtained between group I and II concerning the number of patients in whom induced atrial fibrillation with conduction by the accessory pathway and RR < or = 250 msec was found (0 vs 6, p = 0.0045). No differences were obtained among the anterograde refractory period, the induction of atrial fibrillation independently of the type of atrioventricular conduction, and the induction of atrioventricular reentrant tachycardia and or atrial flutter. The induction of atrial fibrillation was attained during the Scanning/DDT protocol phase in 7 patients in whom this arrhythmia was found with conduction by the accessory pathway and in 2 without preexcitation. All the induced sustained supraventricular arrhythmias were converted by intravenous flecainide. CONCLUSIONS: (1) Only the symptomatic patients have a high risk profile which suggest that electrophysiologic testing do not need to be performed in those with no symptoms. (2) As atrial vulnerability is higher in patients with induced atrial fibrillation and conduction by the accessory pathway, a more intensive ambulatory control seems to be necessary. (3) The results of intravenous flecainide administration on the treatment of sustained induced supraventricular arrhythmias, advocate its use during the electrophysiologic procedures in patients with ventricular preexcitation and WPW pattern. PMID- 8512729 TI - [Necropsy study of the mitral valve according to 5 different echocardiographic planes]. AB - PURPOSE: To study, in anatomic specimens, the regions of the mitral valve transected by the parasternal long axis, the apical five chamber, the apical four chamber, the apical two chamber and the left ventricle apical long axis echocardiographic views. METHODS: 15 patients' hearts, after fixation through intra-ventricular injection of formalin, were cut according to the five above referred echocardiographic views. RESULTS: Only the apical five chamber view studied adequately the most anterior regions of both mitral cusps. The apical four chamber and the parasternal long axis views examine the most posterior segments of the mitral valve. Heart sections made according to the apical two chamber view are not adequate to study both cusps on a anatomo-pathologic view. The left ventricle apical long axis is the one which better defines the length of both cusps. CONCLUSIONS: Its necessary to know precisely the regions of the mitral valve sectioned by different longitudinal echocardiographic views in order to visualize through that method localized mitral valve prolapse. PMID- 8512730 TI - [Multiple aneurysms of the coronary arteries. Report of a case]. AB - Multiple coronary aneurysms are rare. We report a case of a 56 year-old patient and make a state of the art on this subject, discussing etiologic and pathogenic considerations versus clinical and therapeutic aspects. PMID- 8512731 TI - [Cardiovascular syphilis. Report of 2 cases]. AB - We present two cases of cardiovascular syphilis being one of them a curious case of chronic pericardial effusion associated with cardiovascular complications of lues. In this article we will make as well a review of cardiovascular syphilis. PMID- 8512733 TI - Survival of Danish cancer patients, 1943-1987. PMID- 8512732 TI - [Role of superoxide dismutase in the reduction of reperfusion injury of the ischemic myocardium. Lessons of the first experimental animal models]. AB - Myocardial reperfusion is today the best alternative to save ischemic myocardium. However, reperfusion carries with him an aggressive potential that may mask its benefits. From a clinical point of view, it is necessary to create new complementary therapies to prevent such injury. One of such therapy in which a great deal of knowledge in experimental models has been accumulated is superoxide dismutase. In this work are presented some chemical, biological, and pharmacological characteristics of this enzyme. Several forms of reperfusion injury are discussed as well as the role of superoxide dismutase in their prevention. The experience gathered along the years is still small for prevention of cellular oedema, intramyocardial haemorrhage, and low/no-reflow. There is still some controversy about the role of superoxide dismutase in the reduction of myocardial necrosis. However, superoxide dismutase seems to be highly protective, as far as stunned myocardium and reperfusion arrhythmias are concerned. PMID- 8512734 TI - Survival of Danish cancer patients 1943-1987. Female genital organs. AB - In Denmark, about 1800 new cases of cancer of the female genital organs (i.e., uterine cervix, uterine corpus and ovary) occur every year. The similarity in incidence contrasts with the differences in survival patterns for these three cancer types, the crude five-year survival rates being 59% (cervix), 68% (corpus) and 27% (ovary). An overall increase in relative one-, two- and five-year survival rates was observed for cancers of the cervix, corpus and ovary between 1943 and 1987. For uterine cervical cancer there has been an equal improvement in one-, two- and five-year survival rates (12, 11 and 14%), whereas for uterine corpus cancer a greater improvement was seen in the five-year rates (19%) than in those one year after diagnosis (10%). These figures are contrasted by those for ovarian cancer, for which the improvement in one-year survival rate (21%) was nearly twice that for the five-year survival rate (12%). For all the three cancer types, the age at diagnosis increased significantly over the past 40 years. The improvement in survival from cancer of the uterine corpus was most pronounced for older women whereas that for ovarian cancer was greatest among women aged 59 or less. After 1970, there was a decrease in survival rates after cervical cancer among women 60 years or older at the time of diagnosis. This is in contrast to the pattern for younger women (less than 40 at diagnosis), whose survival rate has increased continuously since 1943. PMID- 8512735 TI - Survival of Danish cancer patients 1943-1987. Male genital organs. AB - This chapter describes the survival of men with the two commonest cancers of the genital organs--cancer of the prostate and cancer of the testis. Prostatic cancer is largely a disease of old age and occurs at a rate of about 1400 new cases per year in Denmark. Testicular cancer is a rare disease, usually affecting men in their 20s and 30s. About 250 new cases occur annually in Denmark. Both prostatic and testicular cancer have been increasing in incidence over the period of cancer registration in Denmark. Relative survival of prostatic cancer patients improved over the period of study, with an increase in one-year survival from 52% around 1945 to 80% around 1985. The corresponding change in five-year survival was from 22 to 39%. The survival of testicular cancer patients increased in response to improvements in therapy: relative one-year survival increased from 70% around 1945 to 95% around 1985. The increase was particularly strong for non-seminomas, for which one-year survival increased from 53 to 94%. Excess mortality after a diagnosis of testicular cancer was most pronounced in the first few years after diagnosis; for prostatic cancer, mortality relative to that of the general population was about two fold, even 10 years after diagnosis. PMID- 8512736 TI - Survival of Danish cancer patients 1943-1987. Urinary tract. AB - The 15,160 males and females diagnosed with kidney cancer in Denmark in the period 1943-87, and eligible for inclusion were covered in the analysis. Crude and relative five-year survival from this cancer has improved with calendar time, especially for men. For patients diagnosed in 1943-47, the relative five-year survival was 18% for men and 29% for women; for those diagnosed in 1983-87, it had improved to 35 and 36%, respectively. Patients with localized tumours at the time of diagnosis had a more favourable prognosis than those with disseminated disease, with a five-year survival of 51% for men and 53% for women; people of each sex with metastatic disease had a five-year survival of only 3%. Treatment of kidney cancer throughout the period was surgical removal of the kidney and lymph nodes. The moderate improvement in survival seen with calendar time may be due to better, more efficient surgical techniques. The 32,701 patients diagnosed with cancer of the urinary bladder in 1943-87 and included in the study experienced a marked improvement in crude five-year survival: for both men and women, from 24% for patients diagnosed in 1943-47 to 47% for those diagnosed in 1983-87. Patients whose tumours were localized at the time of diagnosis in 1978 87 had a more favourable prognosis, with survival after 10 years of 36% (men) and 43% (women), than patients with metastatic disease with 10-year survival of less than 1% (men and women). The treatment of bladder tumours underwent a number of changes during the study period. The improvement in survival with calendar time may be due to more efficient treatment, although registration artefacts cannot be excluded. PMID- 8512737 TI - Survival of Danish cancer patients 1943-1987. Malignant melanoma of the skin. AB - Survival after malignant melanoma in Denmark has improved remarkably in all age groups and people of each sex over the last 30 years. During the study period 1943 87, the proportion of patients presenting with an earlier stage of disease at the time of diagnosis increased. No major change has taken place with respect to treatment. Extent of disease, age and sex exerted a steady influence on survival during the study period. Melanoma patients with localized disease had a far better survival expectancy than those with disseminated disease at the time of diagnosis. Age at time of diagnosis had a clear impact on subsequent survival, younger patients having a better prognosis than older ones. In all age groups, women had a higher relative survival rate than men. PMID- 8512738 TI - Survival of Danish cancer patients 1943-1987. Eye, brain and nervous system, thyroid, bone and connective tissue. AB - The cancers covered in this chapter are those of the eye, brain and nervous system, thyroid, bone and connective tissue. Generally, detailed interpretations of data on cancers of the bone and connective tissue are inadvisable owing to small numbers of patients and major changes in diagnosis and registration over time. A slight but steady increase in survival was observed among patients diagnosed in 1943-87 with cancer of the eye. Relative five year survival increased from 60 to 68% in men and from 61 to 74% in women during the 45-year period. The predominant type of eye cancer seen in children, retinoblastoma, had a very favourable prognosis, with a relative five year survival rate of more than 80% since around 1960. Since that time, overall survival for patients with cancers of the brain and nervous system also increased. Relative five year survival improved from 25 to 36% in men and from 34 to 48% in women during 1960 85. Our data do not indicate to which extent therapeutic and diagnostic advances underlie the improvement in survival. Overall survival of patients with thyroid cancer also increased during 1943-87. Relative five-year survival improved from 26 to 58% in men and from 28 to 68% in women. Some of the improvement reflects earlier diagnosis of localized tumours, particularly in young women. A substantial improvement in survival was observed among children and adolescents (< 20 years) diagnosed in 1943-87 with primary bone cancers. Over the study period, the relative five-year survival in that age category and increased from 25 to 48% in males and from 16 to 52% in females. Use of adjuvant chemotherapy in cases of Ewing's sarcoma and osteosarcoma contributed importantly to the improvement in prognosis. Overall survival of patients with soft-tissue cancer associated with no specific organ increased until approximately 1970, after which time no further improvement was observed. The decreased survival seen in women during the last decade of the study is puzzling; the increase in mean age at diagnosis would only partially explain it. PMID- 8512739 TI - Survival of Danish cancer patients 1943-1987. Lymphatic and haematopoietic tissues. AB - In Denmark, 6.6% of all malignant neoplasms among men and 5.5% among women occur in the lymphatic and haematopoietic tissues. Most are generalized when diagnosed, although lymphomas are sometimes confirmed to one region. Treatment has been predominantly by chemotherapy since the 1960s, and is often combined with radiation for lymphomas and myeloma. The five-year survival rates for non Hodgkin's lymphoma improved by 20% between 1970 and 1987. An improvement in survival from Hodgkin's disease began earlier, with a relative five-year survival rate of about 30% in 1960 and of 72% in 1983-87. Survival was better for younger patients (< 50 years) with stage I-II disease, the relative five-year survival rates being 83-93% in 1983-87. For cases of leukaemia much of the improvement in survival rates was founded in 1960s on success in the treatment of childhood leukaemia (acute lymphatic leukaemia); the relative five-year survival rates for children under 10 years of age increased from 12% to 75-80%. Smaller improvements were seen in survival from other types of leukaemia, including the chronic forms. Thus, even for chronic lymphocytic leukaemia, which has a favourable prognosis but is regarded as incurable, improvements in survival rates were seen, which may be attributed to chemotherapeutic treatment or earlier diagnosis. It was not surprising that the dramatic improvement in survival rates coincided with the introduction of chemotherapeutic treatment regimes, as reported previously in clinical series. Acute and chronic cytotoxic side-effects are of concern, and, since both cytotoxic drugs and radiation are potent carcinogens, second primary cancers have been reported to be induced by treatment of cancers (Storm & Prener, 1985). The improvements in the survival rates for the haematopoietic malignancies, however, outweigh the de novo cancer risk related to therapy. PMID- 8512740 TI - Survival of Danish cancer patients 1943-1987. Material and methods. PMID- 8512741 TI - Survival of Danish cancer patients 1943-1987. Digestive organs. AB - Cancers of the digestive organs and peritoneum constituted 28% of all cancers in Denmark in 1943-87. The lack of a common trend in incidence rates for the different tumour types indicates different aetiologies. Survival is worst for cancer of the oesophagus and improves gradually for cancer of the stomach, cancer of the small intestine and colorectal cancers. Survival from these tumours differ little between the sexes, but females have a slightly more favourable prognosis, which is most pronounced for sites with the best survival. The changes in survival over the study period, 1943-87, show virtually no change in the prognosis for oesophageal cancer, very slight, if any, improvement in that for stomach cancer, a detectable improvement in survival from cancer of the small intestine and substantial improvements in survival from colorectal cancer. Survival rates after colorectal cancer appear to be lower in Denmark than those seen in the USA. This finding may be due to the exclusion of certain precancerous lesions from the Danish material, which is not possible in US studies. Cancers of the liver, gallbladder and pancreas all carry extremely high mortality rates, with five-year survival rates below 5%, and one-year survival rates below 5% for cancers of the liver and pancreas. PMID- 8512742 TI - Survival of Danish cancer patients 1943-1987. Respiratory system. AB - Cancers of the respiratory system are among the most common types of malignant neoplasms in the industrialized world. Thus, this group constitute about 20% of all male and about 8% of all female cancers diagnosed in Denmark during the recent years. Altogether respiratory cancers contribute with around 3,700 (14%) new cases of the about 26,000 cancers diagnosed a year, including skin cancers. Since lung cancer, which in general have a very bad prognosis with a relative 5 year survival of 6%, is the far major cancer subtype in the respiratory system (about 90% of all respiratory cancers), the survival of all respiratory cancers combined is poor. However, the survival of the relative rarely sinonasal and laryngeal cancers are fairly good with 5-year relative survival rates in men of 47% and 61% and in women of 51% and 62%, respectively, during the 1980s. In general, only very small improvements in survival during the period of registration have been observed, the largest being in sinonasal neoplasms, where the 5-year relative survival for the men have increased from 18% around 1945 to 47% around 1985, and for the women from 30% around 1945 to 51% around 1985. Since the aetiology of the major part of respiratory cancers is fairly known, i.e. especially tobacco smoking and to some extent several factors in the working environment, it seem most likely that the major progress will come from primary prevention. PMID- 8512744 TI - Survival of Danish cancer patients 1943-1987. Breast. AB - Survival from breast cancer was examined in approximately 76,000 women and 600 men diagnosed in Denmark between 1943 and 1987. About 5% of patients mainly known from death certificates only were excluded from the analysis. Overall, survival improved with time, the relative five-year survival rates increasing from 47 to 69% in women and from 40 to 58% in men. Women had significantly better survival than men. Age at diagnosis was a prognostic factor in women as well as in men, the survival rates decreasing with increasing age at diagnosis. This age effect persisted after stratification for extent of disease. Although it was not demonstrated that the proportion of early-stage breast cancers increased with time, the improvement in survival may be related to increased diagnostic activity. The introduction of adjuvant breast cancer therapy has also improved survival, particularly among women aged less than 45. PMID- 8512743 TI - Survival of Danish cancer patients 1943-1987. Buccal cavity and pharynx. AB - Cancers of the buccal cavity and pharynx are anatomically related and (with the exception of cancers of the salivary glands and nasopharynx) share risk factors, i.e., tobacco and alcohol. For cancers of the lip ("lipstick area") exposure to sunlight is also an important risk factor. Cancers of the buccal cavity and pharynx are rare tumours, accounting for less than 2% of all malignant tumours in Denmark. The largest group is lip cancers (6545 cases in 1943-87) for which the survival rate remained high during the study period, 95-99% of patients surviving longer than five years. Survival from cancer of the tongue (1555 cases in 1943 87) and cancer of the mouth (2770 cases) also remained fairly constant during the period; the relative one-year survival rate for males were 57% for tongue cancer and 75% for mouth cancer in 1983-87. Survival (Kaplan-Meier estimates) from cancers at either site diagnosed in 1978-87 was better for females than for males; however, relative mortality was higher among males than among females for cancer of the tongue (16.3 after one year compared to 11.9 among females), while relative mortality for mouth cancer was 8.9 and 7.8, respectively. After five years, relative mortality was 1.6 and 2.6 for male patients and 1.7 and 1.6 for female patients with cancer of the tongue and mouth. Five-year survival rate after cancer of the salivary glands (2147 cases) fell from 73 in males and 81% in females in 1943-47 to 45 and 71% in 1983-87. During the same period, however, the incidence rate almost halved, and patients were generally older at presentation, with more advanced tumours. The one-year survival rate from tumours of the pharynx (2948 cases; 38% in the tonsils, 28% in the naso-pharynx and 25% in the hypopharynx) increased between 1943 and 1987 from 48% in males and 48% in females to 59% and 67%. After five years, relative mortality was still high in both males (2.5), and females, (4.9). PMID- 8512745 TI - Antioxidants inhibit stimulation of HIV transcription. AB - In studies presented here, we demonstrate that antioxidants regulate NF-kappa B activation and signal transduction pathways leading to HIV expression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant and an efficient glutathione (GSH) precursor, inhibits NF-kappa B activation and HIV expression under conditions in which GSH is depleted and NAC cannot be converted to GSH, (2) that the D-stereoisomer of NAC and a wide variety of chemically unrelated antioxidants also inhibit NF-kappa B activation and/or transcription directed by the HIV LTR, and (3) that depletion of GSH, the principal intracellular antioxidant, augments HIV production in an acute infection model. Taken together, these findings suggest direct antioxidant action as the mechanism for inhibition of HIV transcription by NAC. They also confirm that GSH, acting in its capacity as an antioxidant, regulates HIV expression and that exogenous antioxidants can potentiate this regulation. PMID- 8512746 TI - Simultaneous amplification of multiple HIV-1 DNA sequences from clinical specimens by using nested-primer polymerase chain reaction. AB - A sensitive and specific polymerase chain reaction (PCR) protocol with nested primers was developed for simultaneous amplification of three independent human immunodeficiency virus type 1 (HIV-1) DNA sequences from clinical specimens. DNA samples were first amplified with gag, pol, and env outer primer pairs and then with the corresponding three inner primer pairs in the same two-step reaction. Detection of the different amplification products was readily accomplished by simple agarose gel electrophoresis of the reaction product, even when starting with a single copy of HIV-1 DNA. Equivalent amounts of the three PCR products were generated, provided that the relative concentrations of the inner primer pairs were optimized. In addition, a beta-globin control primer pair could be conveniently included in the internal amplification step to verify that the DNA sample was suitable for PCR analysis. One nested multiplex PCR test was sufficient to detect HIV-1 DNA in all of 80 HIV-1-seropositive individuals and none of 50 HIV-1-seronegative healthy blood donors. The nested multiplex PCR procedure provides an attractive means for simple, rapid, and cost-effective direct detection of HIV-1 DNA in patient samples. PMID- 8512747 TI - Cotransfection of HIV-1 molecular clones with restricted cell tropism may yield progeny virus with altered phenotype. AB - Seven infectious molecular clones were obtained from a human immunodeficiency virus type 1 isolate with rapid/high replicative capacity. Biological characterization of progeny viruses obtained after transfection of clones into peripheral blood mononuclear cells showed that six clones yielded virus with restricted cell tropism, whereas one clone yielded virus able to replicate in cell lines. Although transfection of each of the clones 12, 13, and 82 individually gave rise to viruses with restricted tropism, viruses recovered from cotransfection of the mixtures of these clones exhibited altered phenotype, inasmuch as they were able to replicate in cell lines. To test whether recombination and/or complementation has taken place in the mixture of clones 12 + 13 + 82, the progeny virus was diluted to end point in 15 parallel series. Viruses with diverse biological phenotypes were recovered. With the help of distinctive restriction enzyme markers in regions comprising the vpu/env junction and variable regions 4 and 5 (V4/V5) of the env gene, recombinant genotypes could be identified with high frequency. No particular biological phenotype could be linked to a certain genotype in this study. The results show that different coexisting variants may interact and thereby influence the biological phenotype of a viral population. PMID- 8512748 TI - Human immunodeficiency virus type 2 multiply spliced transcripts. AB - Viral transcripts, particularly those of the regulatory genes (e.g., rev) in lymphocytic cells chronically infected with human immunodeficiency virus type 2, consist of two types, differing in the structure of the leader sequence derived from the 5' long terminal repeat (LTR). Some transcripts undergo a specific splicing event within the 5' LTR, removing an intron consisting of a part of the R region whereas others do not. Because this spliced-out R region is a part of the trans-activation response element (TAR), it could influence trans-activator (Tat)-mediated trans-activation of viral gene expression. Moreover, this part of the R region is predicted to contain a stable secondary structure that could affect the efficiency of translation of the transcripts without this splicing. Thus, the 5' LTR splicing could have important consequences for virus replication, latency, and pathogenicity. PMID- 8512749 TI - Comparative analysis of HTLV-I promoter activities reveals no disease-linked pattern of expression. AB - To investigate the possibility of an association between the type of pathology caused by HTLV-I and the activity of its promoter, we compared the levels of transcription obtained with six LTRs isolated from patients with two different HTLV-I-related diseases: ATL and TSP/HAM. The patients came from different geographical endemic areas. The LTR region was amplified by polymerase chain reaction (PCR) from the DNA of uncultured peripheral blood lymphocytes, and directly cloned upstream of the luciferase reporter gene. Constructs were tested by a transient transfection assay in a variety of cell lines. Although the activities of these LTRs were statistically different in some of the cell lines tested, no correlation could be demonstrated between the promoter activity and the nature of the disease. Thus, the data suggest that the LTR is not a major determinant of the nature of the disease associated with the infection by HTLV-I. PMID- 8512750 TI - Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AB - The gag-homologous region of the human endogenous retrovirus K10 (HERV-K10) was amplified by PCR from human genomic DNA and was analyzed by DNA cloning, sequencing, and expression of open reading frames in the prokaryotic pATH expression system. The analysis of genomic DNA of three donors provided evidence that HERV-K10 genes contain an open reading frame of 1966 bp spanning the entire gag-homologous region. In the prokaryotic system the entire reading frame of the HERV-K10 gag gene could be expressed as a fusion protein exhibiting a molecular weight of about 110,000. In addition, when the gag-homologous region and the adjacent HERV-K10 protease gene were prokaryotically expressed, we observed a Gag protease fusion protein that exhibited specific autoproteolytic activities and processing of HERV-K10 Gag protein. By introducing deletions on the right end of the putative protease gene an autocatalytic site could be localized within 300 bp of the putative HERV-K10 protease gene. For the first time, these results provide evidence that the HERV-K10 encodes a full-length Gag protein and a functional protease. PMID- 8512751 TI - Phylogenetic and serological characterization of two Ugandan HIV-1 isolates. AB - HIV-1 isolates Ug06 and Ug23 were established in culture from peripheral blood mononuclear cells (PBMCs) of Ugandan subjects. The isolates were studied for phylogenetic and serological relationships with each other and with the laboratory strains, HTLV-IIIB and HIV-1MN. The results suggest that the Ugandan isolates are related to different subgroups of African viruses with 17.3% of genetic distance between UG06 and the U455 provirus (Uganda); and 12.6% of genetic distance between UG23 and the JY1 provirus (Zaire). Analysis of the predicted amino acid sequences for Ug06 and Ug23 showed marked sequence heterogeneity in the V3 region and CD4-binding site. A conserved amino acid sequence was identified in the C-terminal immunodominant region of the envelope glycoprotein gp120. The isolates were compared in virus-neutralization experiments with HTLV-IIIB and HIV-1MN stocks, using panels of Western blot positive North American and Ugandan sera. The North American serum samples showed broad neutralizing activity against both of the Ugandan isolates. However, the Ugandan serum panel demonstrated strain-specific activity against either Ug06 or Ug23. Furthermore, the African serum specimens showed higher prevalence and titers of neutralizing activity against the HIV-1MN stock as compared with HTLV IIIB. PMID- 8512753 TI - Understanding the meaning of wounds. AB - Little research has been done to address patients' understanding of wounds and how that might interfere with treatment and healing. This article tackles the issue by examining the meaning of wounds to patients. The origin of the wound and the patients' environment can make a difference to how patients view treatment and healing. The author identifies how this knowledge can be incorporated into nurses' assessment of wounds. PMID- 8512752 TI - Sequence analysis of the gp120 region of the env gene of Ugandan human immunodeficiency proviruses from a single individual. AB - DNA sequences encoding the surface glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) were amplified by the polymerase chain reaction (PCR) from peripheral blood mononuclear cells obtained from a Ugandan AIDS patient. The PCR-amplified DNA was cloned into a phagemid vector and nine clones sequenced. The gp120 sequences of the proviruses were similar to that of the Zairian isolate HIV-JY1 and unlike that of another Ugandan provirus, U455. Six of the clones were closely related to each other (maximum nucleotide sequence divergence 1.9%), and had a V3 amino acid sequence similar to that frequently seen in recent isolates from Uganda. Two others formed a second group that diverged from the first by an average of 6.0% at the nucleotide level, resulting in a 12.5% divergence of amino acid sequence. These divergent clones had extensive amino acid sequence changes not only in the V3 region, which was highly atypical, but also in V1 and V4, and to a lesser extent in V2 and V5. A further proviral clone had a sequence intermediate between those of the other two groups of clones. PMID- 8512754 TI - Pressure sore risk in operating theatres. AB - Little information is available on the genesis of intraoperative pressure sores. A pilot study was set up to investigate whether it is necessary, to prevent pressure sores developing in the operating department. Skin assessments and Braden score readings were taken pre-operatively and post-operatively. Half of the 26 patients had skin changes pre-operatively and there was a 'theatre generated' incidence of 12.5 per cent. The author concludes that further investigation should be commenced. PMID- 8512755 TI - Good clinical practice: a question of balance. PMID- 8512756 TI - The use of proprietary medicines by patients presenting with peptic ulcer haemorrhage. AB - 1. Medication, social and symptom histories were compared in patients with severe haemorrhage from a peptic ulcer (n = 71) and matched control subjects. Self medication with proprietary agents was catalogued in addition to therapy prescribed by general medical practitioners. 2. Prior to the bleed, only 4% of ulcer patients had been free of symptoms normally associated with peptic ulceration, whereas 76% of the control group had been asymptomatic. 3. Gastro irritant proprietary medicines were used regularly by 23% of ulcer patients compared with only 4% of controls. However, proprietary antacids were used chronically by 46% of ulcer patients compared with only 7% of controls. Bicarbonate was the antacid of choice used by 13% of ulcer patients. The odds ratio for the association between development of bleeding peptic ulcer and the use of indigestion remedies was 11.5% (95% CI 1.1, 121). 4. Fifty-one percent of ulcer patients were prescribed agents known to cause gastro-intestinal damage, whereas only 25% of the control group were prescribed similar agents. Only 7% of the control group were prescribed anti-ulcer therapy compared with 37% of those with bleeding ulcer. 5. A large proportion of patients with haemorrhage from a peptic ulcer had had symptoms sufficient to warrant recourse to self-medication with antacids without medical knowledge. Exacerbation of peptic ulcer by self medication with proprietary products is likely to be of lesser significance. PMID- 8512757 TI - Non-steroidal anti-inflammatory drugs and hypertension in the elderly: a community-based cross-sectional study. AB - 1. Whether non-steroidal anti-inflammatory drug (NSAID) usage in the elderly elevates blood pressure or antagonises the blood pressure-lowering effect of antihypertensive medication is presently unknown. The primary aims of this study were to estimate the prevalence of NSAID usage, to evaluate the prescription of NSAIDs for arthritis and to determine whether NSAID usage was an independent predictor of hypertension in a large elderly community. 2. All non institutionalised elderly (> 60 years) residents of Dubbo, NSW who attended for a baseline assessment were enrolled (1237 males, 1568 females). A questionnaire was administered and blood pressure was measured according to the Prineas protocol. The frequency of NSAID usage was determined, with stratification by age, sex, blood pressure group and history of arthritis. 3. NSAID usage was 26% overall (females 28%, males 23%), increased with age and was higher in females than males for every age group studied. Amongst patients with a past history of 'arthritis', 45% were using NSAIDs. Twelve percent were taking NSAIDs and antihypertensive medication concurrently, constituting the population at risk of an adverse drug drug interaction. Employing a multiple logistic regression model which adjusted for several confounders in the cross-sectional analysis, NSAID usage significantly predicted the presence of hypertension (odds ratio: 1.4, 95% confidence interval: 1.1-1.7) with an attributable risk of 29%. 4. Amongst non institutionalised elderly persons, NSAID usage may be an independent risk factor for hypertension. Considering the substantial consumption of NSAIDs by elderly patients, physicians should review their NSAID prescribing patterns for this community group. PMID- 8512758 TI - The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Effect of cimetidine. AB - 1. The pharmacokinetics of 500 mg naproxen given orally were described in 10 subjects using a direct h.p.l.c. analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. 2. The mean elimination half life of naproxen was 24.7 +/- 6.4 h (range 7 to 36 h). 3. Naproxen acyl glucuronide accounted for 50.8 +/- 7.3% of the dose recovered in the urine, its isomerised conjugate isoglucuronide for 6.5 +/- 2.0%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4%, and its isoglucuronide for 5.5 +/- 1.3%. Naproxen and O-desmethylnaproxen were excreted in negligible amounts (< 1%). 4. Even though the urine pH of the subjects was kept acid in order to stabilize the acyl glucuronides, isomerisation took place in blood. 5. The extents of plasma binding of the unconjugated compounds were 98% (naproxen) and 100% (O-desmethylnaproxen), while naproxen acyl glucuronide binding was 92%; that of its isomer isoglucuronide 66%. O-desmethylnaproxen acyl glucuronide was 72% bound and its isoglucuronide was 42% bound. 6. Cimetidine (400 mg twice daily) decreased the t1/2 of naproxen by 39-60% (mean 47.3 +/- 11.5%; P = 0.0014) from 24.7 +/- 6.4 h to 13.2 +/- 1.0 h. It increased (10%) the urinary recovery of naproxen acyl glucuronide (P = 0.0492). The urinary recoveries of naproxen isoglucuronide and O desmethylnaproxen acyl glucuronide remained unchanged. PMID- 8512759 TI - The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-5 HT from human perfused platelets. AB - 1. m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2. Platelets from healthy male volunteers were loaded with [3H]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37 degrees C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5. We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action. PMID- 8512760 TI - Plasma concentrations and ocular effects of cyclopentolate after ocular application of three formulations. AB - 1. Eight volunteers received in randomized order two 30 microliters drops of either 1% w/v cyclopentolate hydrochloride or a corresponding amount of cyclopentolate polygalacturonate in saline or in acetate buffer in one eye. Cyclopentolate concentrations in plasma were measured by a radioreceptor assay. 2. Peak plasma drug concentrations of about 3 ng ml-1 occurred within 30 min after all formulations. Occasionally, a second concentration peak in plasma, probably reflecting drug absorption from the gastrointestinal tract, was seen after 2 h. The mean elimination half-life of cyclopentolate was 111 min when all subjects and formulations were considered together. There were no statistically significant differences between the formulations with respect to the time-course of plasma drug concentration. 3. The maximal mydriatic effect was reached within about 15 min and was maintained for several hours, often being 1/3 of its peak value after 30 h. Similarly, an intense cycloplegic response was achieved within a few minutes, the peak changes in the near-point of vision being 9 to 10 dioptres. The cycloplegic response was more intense after one of the polygalacturonate complexes, especially at later time points. PMID- 8512761 TI - A comparison of amlodipine with enalapril in the treatment of moderate/severe hypertension. AB - 1. The safety and efficacy of amlodipine vs enalapril as monotherapy was evaluated in patients with moderate/severe hypertension (supine DBP 105-125 mm Hg, SBP 140-220 mm Hg). 2. After 2 weeks placebo treatment 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (15 patients) 5-10 mg, or enalapril (16 patients) 5-20 mg for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Clinic supine systolic blood pressure was reduced from 177 to 152 mm Hg (amlodipine) and 183 to 169 mm Hg (enalapril) (95% CI for the intergroup difference -22.1, 0.3, P = 0.06) after 8 weeks treatment. 4. Clinic supine diastolic blood pressure was reduced from 110 to 93 mm Hg (amlodipine) and 109-102 mm Hg (enalapril) (95% CI for the intergroup difference -17.7, -2.7, P < 0.01) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure. Although the reduction in blood pressure was greater for the amlodipine treated group, the differences between treatments were not statistically significant. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (5), peripheral oedema (3), upper respiratory infection (3) and anxiety (2). The adverse events occurring most frequently in the enalapril treated patients were headache (6), dizziness (3) and upper respiratory infection (2). PMID- 8512762 TI - A comparison of amlodipine with enalapril in the treatment of isolated systolic hypertension. AB - 1. The safety and efficacy of amlodipine and enalapril were compared in patients with isolated systolic hypertension (supine DBP < 95 mm Hg and supine SBP 160-200 mm Hg). 2. After 2 weeks treatment with placebo 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (16 patients) or enalapril (15 patients) for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Mean supine systolic blood pressure was reduced from 185 to 164 mm Hg (amlodipine) and 183 to 159 mm Hg (enalapril) (95% CI for the difference between the drugs -10.5, 15.3) after 8 weeks treatment. 4. Mean supine diastolic blood pressure was reduced from 86 to 80 mm Hg (amlodipine) and 88 to 80 mm Hg (enalapril) (95% CI for the difference between the drugs -4.9, 7.6) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure, although there was no significant difference between treatments for the reductions in blood pressure. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (2), peripheral oedema (5) and palpitations (2). The adverse events occurring most frequently in the enalapril group were headache (2), peripheral oedema (2), palpitations (2) and dizziness (3). PMID- 8512763 TI - Inhibition of angiotensin converting enzyme with enalapril maleate in infants with congestive heart failure. AB - We studied the inhibition of angiotensin converting enzyme (ACE) in eight infants with congestive heart failure (CHF) poorly controlled with digoxin and diuretics, treated orally with 0.25 mg kg-1 enalapril maleate once a day. Baseline ACE activities were compared between these infants and control children without CHF or ACE inhibitor. Except for one infant who vomited, inhibition of ACE activity was 75.5 +/- 12.2%, 75.5 +/- 10.5% and 51.7 +/- 12.2%, at 4, 12 and 24 h after drug intake respectively. There was no correlation between postnatal age and inhibition of ACE activity. In infants with CHF, mean baseline ACE activity was significantly higher than in control infants (36.4 +/- 7.2 mu ml-1 vs 26.9 +/- 6.9 mu ml-1, P < 0.05). These results were very similar to those seen in adults. PMID- 8512764 TI - Nonsteroidal anti-inflammatory drug toxicity. AB - The nonsteroidal anti-inflammatory drugs continue to be a mainstay of therapy for patients with chronic pain and inflammation. Because large numbers of these drugs are prescribed, even the most unusual adverse reactions are not uncommon. During the past year several reviews have appeared on the problems of nonsteroidal anti inflammatory drug-induced gastroduodenal erosive disease. Several authors have also grappled with the possible uses of concomitant prophylactic therapy to decrease the possibility of an adverse event. Although several of these reviews are well-done meta-analyses of the available literature, others are more personal reflections on this difficult problem. Colitis and other small- and large-bowel adverse reactions to the nonsteroidal anti-inflammatory drugs have also been addressed this year. Unfortunately, there is not much new information on the interesting problem of small- and large-bowel diaphragm formation, which has been thought to be due to nonsteroidal anti-inflammatory drug therapy in certain patients. There are, however, intriguing data on the effects of indomethacin on rat intestine. There has also been useful work on further defining the renal effects of the nonsteroidal anti-inflammatory drugs. In addition, a syndrome of acute renal failure following binge drinking and therapy with nonsteroidal anti inflammatory drugs is discussed. There have been significant articles that have improved our understanding of the various and at times confusing clinical problems of nonsteroidal anti-inflammatory drug-induced adverse reactions. PMID- 8512765 TI - Immunosuppressive drug therapy for rheumatic disease. AB - The role of intravenous and oral cyclophosphamide in treating systemic lupus and Wegener's granulomatosis was examined in several large studies during the past year. Oral cyclophosphamide for 2 months followed by prednisone alone was relatively ineffective in preventing disease progression in lupus nephritis patients with initially abnormal serum creatinine values. A controlled trial in which three regimens for treating lupus nephritis were compared resulted in superiority of long-term intravenous cyclophosphamide therapy over pulse prednisone or short-term intravenous cyclophosphamide. Two open studies describe treatment of neuropsychiatric lupus with pulse cyclophosphamide. Patients with clinical evidence of inflammatory disease of the central nervous system appeared to respond to this therapy even if antiphospholipid antibodies were present. Analysis of a large cohort of patients with Wegener's granulomatosis showed a high incidence of cancer at long-term follow-up as well as a high incidence of recurrence, often several years after induction of remission with cyclophosphamide plus prednisone. Much progress was made in defining the mechanisms of action of cyclosporine. Additional studies examine the role of cyclosporine in necrotizing scleritis complicating rheumatoid arthritis. Concomitant administration of nonsteroidal anti-inflammatory drugs and cyclosporine to rheumatoid arthritis patients resulted in increased short-term deterioration of renal function. Studies of patients with various autoimmune diseases showed an association of the mean, maximal, and cumulative doses of cyclosporine with biopsy-proven nephropathy. Cytarabine was tried at low doses in the treatment of rheumatoid arthritis with improvement in some patients. PMID- 8512766 TI - Management of adolescent idiopathic scoliosis. AB - Knowledge regarding the etiology, natural history, evaluation, and treatment of adolescent idiopathic scoliosis continues to accumulate. Although the etiology of scoliosis remains unknown, spinal cord and brainstem pathology may play a role in its development. Natural history studies have confirmed earlier reports documenting respiratory failure in patients with curves of greater than 110 degrees. Screening tests are becoming more specific, limiting the number of unnecessary referrals. Surgical treatment has been advanced by the introduction of new instrumentation systems that attempt to correct spinal deformity in three dimensions. Unfortunately, problems such as postoperative decompensation have raised new questions that remain only partially answered. PMID- 8512767 TI - Arthroscopic management of meniscal injuries. AB - The use of the arthroscope in the diagnosis, classification, and management of meniscal disorders is the most common use of arthroscopic surgery in the knee. There are numerous recent advances in technology and technique that now permit improved diagnosis and treatment of meniscal disorders by arthroscopy. The management of meniscal disorders involves the diagnostic identification of the type of meniscal lesion by examination, imaging studies, and arthroscopy. Identification of the lesion, in turn, would lead to a decision as to whether removal or reattachment of the torn portion of meniscus should be undertaken. This is an important decision to reach based on the anatomy of the meniscal tear, because preservation of the menisci is important in maintaining stability and in guarding against articular cartilage degeneration of the knee joint. The treatment of meniscal disorders no longer requires hospitalization or prolonged recovery. The future holds promise for office arthroscopy, advances in meniscal repair technique, and meniscal transplantation. PMID- 8512768 TI - Management of infected knee and hip prostheses. AB - Infection following total hip or total knee arthroplasty can be devastating. It can result in instability of the hip or knee, diminished function, amputation, or death. Fulminant infection is unusual. Chronic low-grade infection is more commonly seen clinically. Differentiation of pain in a total hip or total knee replacement from loosening or infection may be difficult. Aspiration of the hip or knee for three aerobic and anaerobic cultures and sensitivities is the most reliable method of diagnosing infection. In the hip joint, aspiration should be performed under radiographic control. Treatment of the infected total hip or total knee by antibiotics alone is ineffective. Debridement of the hip or knee joint with retention of the prosthesis and intravenous antibiotics is successful in 18% to 40% of cases. Resection arthroplasty of the hip or knee usually results in eradication of the infection but leaves a painful, unstable, and shortened extremity and diminished ability to ambulate. Arthrodesis of the knee usually clears the infection but imposes the disability of a stiff knee. Two-stage reimplantation of the hip or knee is the most successful means of treating the infected total hip or knee replacement. In the knee, the success rate with two stage reimplantation is 80% to 97%. In the hip joint, the success rate of two stage reimplantation is 83% to 87%. Recently, debridement of the hip or knee with retention of the prosthesis and the local installation of antibiotics for a prolonged period has been used in cases of acute infection of less than 3 months' duration without evidence of implant loosening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512769 TI - Prosthetic replacement of the arthritic elbow. AB - According to the recent literature, overall, results appear to be improving with elbow prosthetic surgery for severe arthritic problems, most cases being due to rheumatoid disease. However, a significant challenge remains: although data is accumulating, longer-term follow-up and greater numbers of patients need to be assessed before this area of surgical reconstruction emerges from the clinically experimental stage. It can be seen from the literature reviewed here that prosthetic loosening within bone, displacement of the articular surface of the implant, infection, and neurologic deficit, particularly of the ulnar nerve, can be unfortunate sequelae of prosthetic replacement of the elbow for severe arthritis. Osteoarthritis of the elbow is a good deal less common than rheumatoid disease of this joint, and the severe case is sometimes dealt with by prosthetic replacement; an alternative, in well selected cases, is the somewhat less challenging procedure of lower humeral fenestration arthroplasty. Revision of a failed elbow prosthesis can be a difficult challenge for the surgeon; the alternatives in this unfortunate situation are the use of an external brace, resection arthroplasty, or arthrodesis, all of them far from ideal. Many rheumatoid patients who undergo elbow prosthetic surgery have very significant shoulder involvement. Because of painful restriction of rotation of the gleno humeral articulation, in particular, added forces are brought to bear on the elbow, making this one of the important factors in loosening of fully constrained prostheses. So far, there has been no long-term report of combined elbow and shoulder prosthetic replacement in such individuals, which is at present typically performed on separate occasions. PMID- 8512770 TI - Bone cytokines. AB - Cytokines and growth factors are important in bone tissue as mediators of cell-to cell and matrix-to-cell communication. Cytokines also locally mediate the effects of several hormones on bone cells. Indeed, calciotropic hormones modulate the bone-cell production rate of these factors and, conversely, can change the number of receptors for these hormones on bone cells. Most cytokines are active in bone, but the existence of a bone-specific cytokine is still questioned. Recent work has searched for estradiol modulation of osteoblastic cytokine acting on osteoclast differentiation. In mice, increased interleukin-6 production by osteoblasts is responsible for increased bone resorption occurring after ovariectomy. Interleukin-6 could also be an autocrine or paracrine factor in the pathogenesis of increased resorption occurring in giant cell tumor or in Paget's disease. During osteoporosis and age-related bone changes, modifications of the production of insulin-like growth factor I or of one of its binding proteins could be responsible for low bone formation. Interrelationships between cytokines and hormones can affect the action of parathyroid hormone-related peptide on bone cells. The field of implication of cytokines in metabolic bone disease is growing. PMID- 8512771 TI - Epidemiology and risk factors of osteoporosis. AB - Recent osteoporosis research has been oriented increasingly toward understanding the determinants of peak bone mass acquisition during childhood and adolescence. Genetic factors may account for approximately half of the variability in peak femoral bone mass density, and racial differences in bone mass have been shown to appear early in life. Physical activity appears to play an important role in increasing bone mass during childhood. Most fractures in the elderly have been found to be associated with reduced bone mass and could therefore be considered osteoporotic. Retrospective reviews of medical records from residents of Rochester, Minnesota, suggest that approximately one third of women with vertebral deformities seek medical attention. Other cross-sectional data suggest that vertebral deformities cause substantial back pain and disability only if vertebral height ratios fall 4 SD below the mean. PMID- 8512772 TI - Diagnosis and treatment of osteoporosis. AB - Risk of osteoporotic fracture is dependent on peak bone mass achieved at skeletal maturity and subsequent bone loss. Accordingly, reduction in this risk can be achieved by maximizing the peak bone mass, preventing subsequent bone loss, or increasing bone density in patients with established osteoporosis. Recent studies in twins have shown that although peak bone mass is strongly genetically determined, it can be influenced by dietary calcium intake and physical activity. Bone mass gain is rapid during puberty, and delayed puberty may alter peak bone mass. Estrogen therapy can prevent bone loss in postmenopausal women. Bone densitometry can be used to select patients who are suitable for therapy and enhance compliance; however, screening is not justified. Treatment of established bone loss remains a problem, although recent studies of estrogen, vitamin D, and bisphosphonates are encouraging. PMID- 8512773 TI - Paget's disease of bone. AB - In this review, recent studies on the etiology and pathogenesis of Paget's disease, with particular attention to the apparent familial clustering of cases and the possibility of a causal role for viral infection, are discussed. The role of biochemical markers of bone turnover is explored, as well as the value of imaging in confirming the diagnosis, monitoring the effects of therapy, and assessing complications. The bisphosphonates are widely used in the treatment of Paget's disease; experience with newer, more potent second- and third-generation bisphosphonates, as well as potential future roles for calcitonin, are described. Studies on some of the orthopedic effects of Paget's disease are also presented. PMID- 8512774 TI - Renal osteodystrophy and hypercalcemia. AB - The occurrence of aluminum-related bone disease should be completely prevented in uremic patients by restricting the use of aluminum-phosphate binders, which can be safely replaced by oral calcium carbonate. Factors other than aluminum may lead to adynamic bone disease in uremic patients. Radiolucent bone cysts are indicative of amyloid deposits, and their occurrence and progression may be influenced by the membranes used for hemodialysis. Bone disease may persist after successful renal transplantation, and the additional deleterious effect of immunosuppressive drugs should be emphasized. Primary hyperparathyroidism is the most frequent cause of hypercalcemia in the general population. Surgery should be undertaken when there is evidence of active disease, even in asymptomatic patients. The consequences of primary hyperparathyroidism on bone mass and bone fragility remain controversial, and histologic bone studies suggest that hyperparathyroidism leads to increased bone turnover without any deleterious effect on bone volume or trabecular architecture. The diagnostic value of a newly developed immunoassay for intact parathyroid hormone and parathyroid hormone related protein is clearly demonstrated. New bisphosphonates are of major value for the management of hypercalcemia in malignancy. PMID- 8512775 TI - Animal models of bone physiology. AB - Because of the well-known technical difficulties in investigating the histology and physiology of the skeleton, bone physiology is not yet completely understood. Much new information has been obtained in recent years with in vitro investigations, but animal models are widely used when the overall effects of hormones or therapeutic agents or both need to be investigated. In this review, we discuss results obtained over the past year on several not yet completely understood topics. The effect of exercise on bone mass has been stressed by several authors, and at the cellular level, it has been suggested that the inositol cascade is the intracellular transduction pathway for mechanical stimuli. Ovariectomized rat systems have been widely used to demonstrate the protective effect of estrogen against bone resorption, and interesting indications of an estrogen-dependent stimulation of bone formation have been presented. The anabolic effect of low doses of fluoride has also been assessed. PMID- 8512776 TI - Clinical therapeutics. PMID- 8512778 TI - Metabolic bone disease. PMID- 8512777 TI - Orthopedic conditions and surgery. PMID- 8512779 TI - Treatment of progressive metastatic prostate cancer. AB - The optimal therapy for metastatic prostate cancer that has failed initial hormonal therapy poses a significant dilemma for the attending physician. No salvage therapy has proven to be clearly superior. Currently accepted treatment options range from supportive care alone to highly investigational regimens. Recent encouraging results have been reported with investigational agents such as suramin and R. 75251 (Liarozole), and with novel combinations such as estramustine (Emcyt) plus vinblastine. However, there is still no proof that salvage therapy prolongs survival. In a patient population that is older and frequently debilitated, with an expected median survival of 6 months, determinants of therapy should include drug toxicity profiles, frequency of treatment and follow-up studies, and necessity for hospitalization. For patients with good performance status and organ function, participation in clinical trials should be advocated. Quality-of-life issues should be integrated into all clinical trials involving hormone-refractory metastatic prostate cancer. PMID- 8512780 TI - Clinical trials referral resource. Acute lymphocytic leukemia. PMID- 8512781 TI - Neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma. AB - Gastric adenocarcinoma is typically diagnosed at an advanced stage, and even with "curative" gastrectomy, most patients die of recurrent disease. Neoadjuvant chemotherapy for locally advanced gastric cancer is an experimental treatment strategy that may increase resectability and improve survival for patients afflicted with an almost uniformly fatal neoplasm. At our institution, we are evaluating the efficacy of fluorouracil, leucovorin, and interferon alfa-2A administered for three cycles, followed by surgery and consolidation therapy for patients with T3-4, N1-2, M0 gastric adenocarcinoma. The rationale for the use of neoadjuvant therapy combined with radical extirpative surgery in this setting and related issues are discussed. PMID- 8512782 TI - Clarithromycin effectively treats infection in AIDS patients. PMID- 8512783 TI - Radiolabeled monoclonal antibody being studied as "vaccine" in ovarian cancer patients. PMID- 8512784 TI - Cell-killing lipid may provide new cancer treatment. PMID- 8512785 TI - New therapy injects drugs directly into liver tumors. PMID- 8512786 TI - Photodynamic therapy: new applications in skin cancer. PMID- 8512787 TI - Immunotoxin therapy of cancer. AB - Differentiation antigens, hormones and growth factor receptors, and viral antigens are expressed on the surface of a variety of malignant and dysfunctional cells in humans. Murine and human monoclonal antibodies, recombinant hormone and growth factors, and recombinant soluble viral glycoprotein receptors have been generated that can target diseased human cells in vitro and in vivo. Highly potent peptide toxins that catalytically inactivate protein synthesis have been linked both chemically and genetically to these ligands to produce a new class of cancer therapeutic agents called immunotoxins. This article describes the structure, physiology, and initial clinical results with these molecules. Ongoing clinical studies are beginning to define a role for these unique agents in patients with malignancies of minimal bulk in combination with conventional chemoradiotherapy. PMID- 8512788 TI - Cost of HIV care to reach $15 billion by 1995. PMID- 8512789 TI - Update on biochemical modulation of chemotherapeutic agents. AB - Application of biochemical modulation strategies in the clinic has been hampered by many factors, particularly the problem of selectivity. Since modulation strategies rarely exploit biochemical pathways that are unique to tumor cells, increased toxicity to normal tissues may occur. The combination of 5-FU with leucovorin, PALA, or interferon appears to produce response rates in the range of 30% to 40% in patients with advanced colorectal cancer, but only 5-FU plus leucovorin has been shown to be superior to 5-FU alone. Biochemical modulation of cytarabine by hydroxyurea or fludarabine has produced encouraging results in patients with refractory non-Hodgkin's lymphoma and acute leukemia. Further studies are necessary to determine the value of this approach. PMID- 8512790 TI - The differentiated surgical treatment of primary varicosis. AB - A differentiated surgical treatment of primary varicosis of the long and short saphenous veins, according to the type of varicosis, is necessary to avoid significant recurrence. The cosmetic results must also be taken into consideration. Knowing the most frequent types of primary varicosis and the principles of selective surgical treatment, the surgeon is able to perform a curative operation with a low complication rate and level of postoperative morbidity, high compliance, and excellent cosmetic results. PMID- 8512791 TI - Percutaneous minisurgical phlebectomy. AB - Percutaneous Minisurgical Phlebectomy is a safe and effective form of permanent treatment for side-branch varicosis in addition to other varicose veins (except the proximal part of the long saphenous vein) by means of multiple 1 to 2 mm incisions. The operation is performed using local anaesthesia in the outpatient department. There is no need for prophylaxis against thrombosis. Complications are rare and inconsequential. PMID- 8512792 TI - Advanced sclerotherapy treatment of varicose veins with duplex ultrasonographic guidance. AB - Advanced sclerotherapy of varicose veins is described in this article using duplex ultrasonographic guidance in three phases of the process. In the presclerotherapeutic stage, patency and competency of the deep venous system are evaluated, location and morphology of the highest point of reflux are determined, luminal and parietal diameters of the target vein, venous compressibility, leaflets of the incompetent valve, and the degree, extent, and velocity of reflux are assessed. In the sclerotherapeutic stage, ultrasonographic guidance is helpful when the anatomy is intricate and points of reflux would otherwise be inaccessible. In the postsclerotherapeutic stage, duplex ultrasonography is indispensable for determination of the extent of the sclerosing reaction, measurement of luminal and parietal diameters, and to elucidate luminal content and its degree of adherence to the venous wall. Duplex ultrasonography provides a sound basis for clinical decision making and thereby enhances the precision and safety of advanced sclerotherapy. PMID- 8512793 TI - Microsclerotherapy. AB - The full text of the course given at the European School of Phlebology (Paris, France, November 27, 1990), presenting all the aspects of pathology and microsclerosing treatment is offered. Practical technique, material, and hints are presented to help young (or new) practitioners. These protocols are widely used in France and they are based on the works of the Ecole Francaise de Phlebologie founded by Raymond Tournay. Some differences may appear between our methods and other methods proposed in Europe and the United States but the results are, in fact, proven to be very good with very little postsclerotherapic matting and pigmentation. For instance, we do not recommend compression in these cases because it does not improve the results. In this article, the sclerosing agents we discuss are different from those available in the United States but our reflections remain valid and we hope these products will soon be approved for use outside of France. PMID- 8512794 TI - Deep vein thrombosis: the risks of sclerotherapy in hypercoagulable states. AB - There have been many case reports of deep vein thrombosis and pulmonary thromboembolism in patients undergoing sclerotherapy for the treatment of varicose veins, but the true incidence of venous thromboembolism in this patient population is unknown. Patients who develop deep vein thrombosis while being treated for varicose veins do so either because of an error in treatment or because the patient suffers from some underlying hypercoagulable state. It is possible to identify prospectively many patients who are at especially high risk for venous thromboembolism by virtue of genetic predisposition, past or recent medical problems, or environmental factors. When sclerotherapy is used in such patients, special efforts must be made to protect against the development of venous thrombosis during treatment. PMID- 8512795 TI - Setting up a vein treatment center--incorporating sclerotherapy into the dermatologic practice. AB - Sclerotherapy, which uses injectable sclerosants to obliterate varicose and spider veins without surgery, is a relatively simple procedure that can easily be added to an existing practice. This article summarizes the basic requirements for the incorporation of this technique including educational resources, emergency equipment, precautions, documentation, technique, and a comparison of the advantages and disadvantages of commonly used sclerosants. PMID- 8512796 TI - Adverse sequelae of venous hypertension. AB - Venous hypertension and venous ulcers are clinical entities that are expected to increase as the population ages. This article will review the current clinical and laboratory data pertinent to lipodermatosclerosis and venous ulcer development. An understanding of these putative pathophysiologic mechanisms may help the clinician to better diagnose and manage such patients. PMID- 8512797 TI - Venous conditions associated with pregnancy. AB - Pregnancy is associated with several changes in venous physiology. These include relaxation of venous wall tone and increased lower extremity venous pressure. As a result of these changes, varicose veins, spider telangiectasias, purpura, and other superficial findings may develop. Treatment of these conditions is conservative during pregnancy. As the changes in venous hemodynamics resolve over several weeks after delivery, partial or complete regression may occur. In cases where persistent abnormality persists well after delivery, more definitive therapy may be considered. Pregnancy is also associated with a mild hypercoagulable state, and there may be trauma to venous endothelium associated with delivery. Coupled with the relative stasis resulting from pelvic venous compression by the uterus and from decreases in venous tone, these changes cause an increased risk of deep vein thrombosis in late pregnancy and the peripartum period. Anticoagulation with heparin is required as coumadin and fibrinolytic agents are considered to be hazardous. PMID- 8512798 TI - Evaluation of the venous system by Doppler ultrasound and photoplethysmography or light reflection rheography before sclerotherapy. AB - Transmission of high pressure, from deep to superficial venous system of the leg, often causes varicosis of superficial veins. High-pressure transmission frequently occurs through reverse flow or leakage through malfunctioning valves. Therefore, the goal of varicose or telangiectatic vein treatment to stop the leak or reflux at its origin by eliminating vein segments with faulty valves. Noninvasive diagnostic tests such as Doppler ultrasound allow reflux sites to be identified and targeted before treatment. Doppler ultrasound permits assessment of competence of the sapheno-femoral junctions and lesser saphenous-popliteal vein junctions bilaterally and detection of points of reflux through suspected incompetent perforating veins in the thigh, calf, and ankle. Photoplethysmography (PPG), or light reflection rheography (LRR), offers a simple, reproducible technique for physiologic evaluation of the effectiveness of the calf muscle pump and quantification of the degree of venous insufficiency as well as differentiation between superficial and deep venous insufficiency. A combination of Doppler ultrasound and PPG/LRR readily identifies those patients who may derive a medical benefit from treatment of a physiologically abnormal venous system. The presence of reflux by Doppler is indicative of a venous problem that is more than cosmetic. Treatment may consist of sclerotherapy alone or a combination of surgical ligation of an incompetent sapheno-femoral junction followed by sclerotherapy. PMID- 8512799 TI - Mechanism of action of sclerotherapy. AB - An understanding of the mechanism by which diverse chemical solutions can initiate the process of vein-wall disruption and resorption, ie, sclerotherapy, is important when using this technique as a therapeutic modality. Insight into the pathophysiologic changes that this procedure effects within the vein wall can insure maximal clinical efficacy while minimizing the incidence of complications. This article elucidates the factors that determine the extent of mural disruption and the mechanism by which injury is produced. PMID- 8512800 TI - Sclerotherapy treatment of varicose veins. AB - The protocol for clinical examination and diagnostic evaluation of patients with varicose veins is described in this article. The specific techniques of sclerotherapy for treatment of the saphenofemoral junction, sapheno-popliteal junction, incompetent perforators, and truncular and reticular varices is outlined. Recommended dosages for both saphenous and nonsaphenous varicose veins are listed in order to help the practitioner achieve satisfactory sclerotherapy. PMID- 8512802 TI - Cellular accumulation of the anticancer agent cisplatin: a review. AB - Acquired resistance to cisplatin (DDP) is a major clinical problem in the treatment of ovarian, testicular, and head and neck carcinomas; decreased accumulation of DDP is the most consistently observed alteration in resistant cells. It has been postulated that DDP enters the cell by passive diffusion based on the observations that DDP accumulation is proportional to the drug concentration, accumulation is not saturable, and that structural analogs of DDP do not inhibit accumulation. However, recent studies show that DDP accumulation can be specifically stimulated or inhibited by pharmacological agents and the activation of signal transduction pathways. This paper reviews the existing data on the mechanism of DDP accumulation and develops the postulate that some component of transport occurs through a gated ion channel. PMID- 8512801 TI - SR 4233 (tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours. AB - SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide, WIN 59075, tirapazamine) is the lead compound in a new class of bioreductive anticancer drugs, the benzotriazine di-N-oxides. It is currently undergoing Phase I clinical testing. The preferential tumour cell killing of SR 4233 is a result of its high specific toxicity to cells at low oxygen tensions. Such hypoxic cells are a common feature of solid tumours, but not normal tissues, and are resistant to cancer therapies including radiation and some anticancer drugs. The killing of these tumour cells by SR 4233, particularly when given on multiple occasions, can increase total tumour cell killing by fractionated irradiation by several orders of magnitude without increasing toxicity to surrounding normal tissues. Topics covered in this review include the rationale for developing a hypoxic cytotoxic agent, the cytotoxicity of SR 4233 as a function of oxygen concentration, the mechanism of action of the drug and its intracellular target and the in vivo evidence that the drug may be useful as an adjunct both to radiotherapy and chemotherapy. Finally, the major unanswered questions on the drug are outlined. PMID- 8512803 TI - Biological activities of phthalocyanines--XVI. Tetrahydroxy- and tetraalkylhydroxy zinc phthalocyanines. Effect of alkyl chain length on in vitro and in vivo photodynamic activities. AB - Zinc phthalocyanine substituted with four hydroxyl groups attached to the macrocycle, either directly or via spacer chains of three or six carbon atoms, were tested for their photodynamic ability to inactivate Chinese hamster lung fibroblasts (line V-79) in vitro, and to induce regression of EMT-6 tumours grown subcutaneously in Balb/c mice. Their potential to inflict direct cell killing during photodynamic therapy was investigated by examining vascular stasis immediately following photoirradiation using fluorescein as a marker, and also by an in vivo/in vitro EMT-6 cell survival assay. Both of the tetraalkylhydroxy substituted zinc phthalocyanines are effective photodynamic sensitisers in vivo with the tetrapropylhydroxy compound exhibiting about twice the activity of the tetrahexylhydroxy analogue. The differences in activities were accentuated in vitro, the tetrapropylhydroxy compound was two orders of magnitude more potent than the tetrahexylhydroxy analogue in photoinactivating V-79 cells. The tetrahydroxy compound lacking spacer chains failed to exhibit photodynamic activity in either system. Tumour response with the active compounds was preceded by vascular stasis immediate following irradiation which suggests, together with the absence of activity in the in vivo/in vitro assay, that tumour regression involves an indirect response to the photodynamic action rather than direct cell killing. These data demonstrate the importance of the spatial orientation of functional groups around the macrocycle of photosensitisers for their efficacy in the photodynamic therapy of cancer. PMID- 8512804 TI - Monoclonal antibodies reacting with the MUC2 mucin core protein. AB - This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgG1) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone. The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUC1 or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4F1 reacted with this peptide in both assays. Furthermore, 4F1 reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin. Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2. These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours. PMID- 8512805 TI - Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas. AB - V79 Chinese hamster cells expressing either the O6-alkylguanine-DNA alkyltransferase (ATase) encoded by the E. coli ogt gene or a truncated version of the E. coli ada gene have been exposed to various alkylnitrosoureas to investigate the contribution of ATase repairable lesions to the toxicity of these compounds. Both ATases are able to repair O6-alkylguanine (O6-AlkG) and O4 alkylthymine (O4-AlkT) but the ogt ATase is more efficient in the repair of O4 methylthymine (O4-MeT) and higher alkyl derivatives of O6-AlkG than is the ada ATase. Expression of the ogt ATase provided greater protection against the toxic effects of the alkylating agents then the ada ATase particularly with N-ethyl-N nitrosourea (ENU) and N-butyl-N-nitrosourea (BNU) to which the ada ATase expressing cells were as sensitive as parent vector transfected cells. Although ogt was expressed at slightly higher levels than the truncated ada in the transfected cells, this could not account for the differential protection observed. For-N-methyl-N-nitrosourea (MNU) the increased protection in ogt transfected cells is consistent with O4-MeT acting as a toxic lesion. For the longer chain alkylating agents and chloroethylating agents, the protection afforded by the ogt protein may be a consequence of the more efficient repair of O6-AlkG, O4-AlkT or both of these lesions in comparison with the ada-encoded ATase. PMID- 8512806 TI - Cytokinetic analysis of lung cancer by in vivo bromodeoxyuridine labelling. AB - Cytokinetic parameters of various types of lung cancer were determined in bronchoscopy specimens after in vivo labelling with the thymidine analogue bromodeoxyuridine (BrdU). The S-phase fraction and BrdU labelling index were measured flow cytometrically, allowing calculation of the S-phase transit time and potential tumour doubling time. The methodology used was found to be feasible for obtaining cytokinetic data from 76% of the bronchial biopsy samples. Despite the difference in clinical behaviour and growth pattern between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), no significant differences were observed between the mean values of the cytokinetic parameters of SCLC and NSCLC. The estimated cell loss factor was higher in NSCLC than in SCLC. It appears that the growth of a tumour, as clinically observed, is to a considerable extent influenced by cell loss. In accord with this assumption is the fact that we have observed non-BrdU labelled S-phase cells, both in tumour biopsies and in apparently normal tissue. The presence of these so-called unlabelled S-phase cells in relation to cell loss is discussed. PMID- 8512807 TI - Intensity of class I antigen expression on human tumour cell lines and its relevance to the efficiency of non-MHC-restricted killing. AB - A modified tetrazolium reduction assay (MTT) was used to assess the relation between HLA class I antigen expression on tumour cells and their susceptibility as a target for non-MHC restricted LAK/NK cytotoxicity using interleukin-2 activated peripheral blood mononuclear cells (MNC) from normal individuals. At 20/1 effector/target ratio this ranged from no killing to 77%. The efficiency of killing was dependent on duration of effector cell culture with IL-2, peaking at day 10 and declining thereafter. This killing could be enhanced by addition of other cytokines including interferons alpha, beta and gamma. Study of a panel of 15 tumour cell lines using a single effector showed that there was no statistically significant inverse correlation (using Spearman rank test) between the degree of tumour class I expression and LAK/NK killing at 20/1 (r = 0.23 P = 0.39) and 10/1 (r = 0.30, P = 0.27) and at 5/1 E/T ratio r = 0.47, P = 0.08) respectively. Lack of inverse correlation between these two parameters came from study of one bladder tumour line (FEN), whose absent class I antigens had been corrected by transfection with beta 2 microglobulin gene. At high E/T ratio (20/1) there was an increase in the susceptibility of target cells to lysis (36% parent cell, 45% transfected cell), whilst at lower E/T ratios (1/1) there was significantly more killing of the non-transfected cells (10% vs 31%). The addition of anti-class I antibody W6/32 increased killing by 18% but this was non specific as the same increase occurred with a class II antibody. These data suggest that overall there was not an inverse correlation between class I expression and LAK/NK killing at high E/T ratios, whilst at low (5/1 or lower) E/T ratios this correlation nearly reached statistical significance suggesting that the conflicting literature reports may be due to a threshold levels of effector cells above which the masking effects of MHC antigens disappears. PMID- 8512808 TI - Caffeine potentiates the lethality of tumour necrosis factor in cancer cells. AB - In this study we have investigated the interaction of caffeine, a prototypic methylxanthine, and TNF on the induction of cell death in mouse and human cell lines during progression from G1 to successive phases of the cell cycle. Exposure of cells to TNF (0.1-100 ng ml-1) as single agent for 48 h caused low or no lethality. The rates of cell death increased significantly when cells cultured with TNF for 24 h were exposed to caffeine (2.5-20 mM). The magnitude of the enhancement by caffeine was TNF and caffeine dose-dependent. The most effective response to this combination was observed in the mouse cell lines, WEHI and L929, followed by the human cell lines, HeLa, A375 and MCF-7, respectively. In L929 cells, TNF treatment did not inhibit DNA synthesis during the first S phase of the cell cycle (20-24 h), but it did block the progress toward a second S phase, indicating the cells were arrested at G2 phase or mitosis. Caffeine had great enhancer effect on L929 cells exposed to TNF for 24 h, but the effect was reduced in cells with either less than 24 h or greater than 28 h of exposure. L929 cells stimulated with TNF died via apoptosis, as judged by both morphological criteria and the occurrence of internucleosomal DNA cleavage. Exposure of TNF-treated cells to caffeine caused a greater increase in the proportion of apoptotic cells as well as the extent of internucleosomal DNA fragmentation. PMID- 8512809 TI - Recombinations of chromosomal bands 6p21 and 14q24 characterise pulmonary hamartomas. AB - Cytogenetic analysis of short-term cultures from seven pulmonary hamartomas revealed an abnormal karyotype in six of them. The most characteristic aberration was an exchange of material between 6p21 and 14q24, found in three tumours. Abnormalities of either 6p or 14q were seen in another two hamartomas. Other regions that were rearranged more than once were 12q (three times) and 17p (twice), sometimes in exchange with 6p or 14q and giving rise to complex derivative chromosomes. Only one tumour had aberrations that did not involve 6p, 12q, 14q, or 17p. These results-together with the data on three previously reported pulmonary hamartomas, two of which also had t(6;14)-show that recombinations between 6p21 and 14q24 are common, and hence probably pathogenetically important. The data support the view that these tumours are genuine neoplasms rather than developmental anomalies. The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band. PMID- 8512810 TI - Targeting of saporin to CD25-positive normal and neoplastic lymphocytes by an anti-saporin/anti-CD25 bispecific monoclonal antibody: in vitro evaluation. AB - This study has been designed to verify the specific toxicity of saporin, a type 1 ribosome-inactivating protein (RIP), with the same activity as ricin A chain, targeted by a bispecific monoclonal antibody (bimAb) recognising both the CD25 antigen and the RIP. The CD25 antigen is expressed by lymphoid populations upon activation and by leukaemias and lymphomas with an activated membrane phenotype (Hodgkin's lymphoma, anaplastic large cell lymphoma, adult T cell leukaemia). The bimAb-saporin mixture was tested on CD25+ targets at different bimAb and saporin concentrations. Saporin, in the presence of a bimAb concentration of 10(-9) M, inhibited protein synthesis by CD25+ neoplastic lymphocytes (L540 and MT2 cell lines) with IC50S (concentrations giving 50% of inhibition) ranging from 8 x 10( 12) M to 3 x 10(-11) M. The saporin-bimAb mixture was also effective in blocking the phytohaemagglutinin-driven proliferation of normal lymphocytes, whereas it displayed the same level of toxicity exerted by saporin alone on an irrelevant CD25-negative cell line (EBV-infected B lymphoblastoid cell line). From these results it is possible to envisage a clinical use of this bimAb as a cytotoxic agent for CD25+ leukaemias and lymphomas, as well as an immunosuppressive agent for severe immune disorders such as graft-vs-host disease (GVHD) and transplanted organ rejection. PMID- 8512811 TI - Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. AB - In order to investigate allele loss in colorectal tumours we have developed a rapid technique which overcomes most of the problems associated with radioactive Restriction Fragment Length Polymorphism (RFLP) analysis of allele loss. We utilise microsatellite length polymorphisms which are highly informative and are closely linked to loci of interest. Sequences containing microsatellites can be amplified from normal and tumour DNA pairs by a polymerase chain reaction (PCR) in which one of the primers is fluorescently labelled. This enables us to detect the products on polyacrylamide gels run on an automated DNA sequencer using dedicated software, by which results are automatically quantitated in terms of peak size, height, and area. Using this technique we have analysed 26 normal tissue: cancer pairs for allele loss at two loci linked to the adenomatous polyposis coli (APC) gene on chromosome 5q. Repeated assays yielded identical results for each pair. Allele loss was found in 10 out of 25 informative samples (40%). PMID- 8512812 TI - Fibroblast stimulation of breast cancer cell growth in a serum-free system. AB - Conditioned media from 14 short term fibroblast cell lines were mitogenic for human breast cancer cells with different steroid receptor profiles in serum-free culture. Fibroblast-conditioned medium stimulated tritiated thymidine incorporation in short term culture and growth in a longer proliferation study as measured by the MTT colorimetric assay. Conditioned media from benign and malignant epithelial cells were non-stimulatory for breast cancer cells but that derived from endothelial cells showed similar stimulation to fibroblasts. Partial purification of fibroblast-conditioned medium identified a peptide with a molecular weight of approximately 8 kDa that showed no affinity for heparin and was mitogenic for MCF-7 breast cancer cells. PMID- 8512813 TI - A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1 cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells. AB - Interstrand cross-linking, repair and lethal effects of (-)-(R)-2 aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) (DWA2114R) were studied in normal human. Fanconi's anaemia (FA) and xeroderma pigmentosum group A (XPA) cells. Interstrand crosslinking by DWA2114R was slower than that by cisplatin (CDDP), since DWA2114R produced mainly Pt(II)-monoadducts after 1 h treatment, followed by progressive interstrand crosslinking to a maximum 5 h post incubation, while CDDP induced rapidly interstrand crosslinks in approximately 70% DNA during the 1 h treatment, followed by a approximately 30% residual increase. At the maximum rate, DWA2114R was 18 times less interstrand crosslinking than CDDP on the 1 mM basis. FA cells were specifically defective in the first half-excision of DWA2114R and CDDP-induced Pt(II) interstrand crosslinks, but XPA cells were as proficient as normal cells (t1/2 = 5-7 h). On the contrary, XPA cells were deficient in excision repair of intrastrand crosslinks, but FA cells were normal. In clonogenic survival curves of all types of cells, mean lethal doses (Do) of DWA2114R were an order of magnitude greater than those of CDDP. FA cells were most (3.5 times) sensitive (Do = 25.1 +/- 0.96 microM) and XPA cells were 1.9 times more sensitive (Do = 47.1 +/- 0.17 microM) to DWA2114R than normal cells (Do = 87.6 +/- 5.65 microM). DWA2114R and carboplatin with a cyclobutanedicarboxylato group exhibited almost similar lethal effects on each of normal, FA and XPA strains. FA (Do = 3.44 +/- 0.44 microM) and XPA cells (Do = 3.84 +/- 0.17 microM) were similarly 3-fold more sensitive to CDDP than normal (Do = 9.97 +/- 0.15 microM). On the basis of a single lethal hit (Do), thus DWA2114R and carboplatin effectively killed more FA cells defective in interstrand crosslink repair than XPA cells defective in intrastrand crosslink repair. PMID- 8512814 TI - Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells. AB - Temozolomide (8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one) has shown promising activity in Phase I trials against some brain (glioma) and skin (melanoma, mycosis fungoides) cancers. Temozolomide and lomustine (CCNU) showed parallel toxicity in seven human tumour cell lines and this generally correlated (correlation coefficients 0.87 and 0.92 respectively) with the level of expression of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase, EC 2.1.1.63). Pretreating cells with the ATase inhibitor, O6-benzylguanine (BG), potentiated cytotoxicity to a similar degree with both drugs, but did not sensitise a cell line (ZR-75-1) expressing very low levels of this protein. When BG pretreatment was combined with repeat doses of temozolomide a dramatic potentiation (300 fold) was seen in MAWI cells, which express high levels of ATase, but not in a cell line (U373) expressing lower levels of ATase. [14C] labelled temozolomide uptake was similar in sensitive and resistant lines. Human ATase-cDNA transfected xeroderma pigmentosum (XP) fibroblasts were more resistant than XP control cells to temozolomide and the related chloroethylating agent mitozolomide and although BG completely suppressed ATase activity in these cells, resistance was still greater than in control cells. PMID- 8512815 TI - Altered phosphorylation status, phospholipid metabolism and gluconeogenesis in the host liver of rats with prostate cancer: a 31P magnetic resonance spectroscopy study. AB - 31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose 6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer. PMID- 8512816 TI - Pharmacokinetic studies in mice with ICI D0490, a novel recombinant ricin A-chain immunotoxin. AB - A colorectal tumour-directed immunotoxin, ICI D0490, has been constructed by linking recombinant ricin A-chain to C242, a mouse monoclonal antibody, by means of a methyl-hindered disulphide bond. Recombinant ricin A-chain and a hindered disulphide linker were anticipated to confer favourable pharmacokinetic properties on the immunotoxin. The pharmacokinetics of ICI D0490 have been studied in mice following single and repeated i.v. administration. The concentrations of intact immunotoxin in mouse plasma at various time intervals after injection for up to 96 h were measured by a solid-phase enzyme-linked immunosorbent assay (ELISA) and the data analysed by both model-dependent (two compartment) and model-independent methods. Following a single i.v. bolus dose of 2.5 mg kg-1 (50% of the LD10 in mice), the clearance of ICI D0490 from the plasma was extremely slow; 34 microliters min-1 kg-1, t1/2 beta = 33 h. Model-dependent and model-independent analyses gave comparable results with steady state volumes of distribution of 93 and 69 ml kg-1, respectively. The two compartment analysis gave an initial volume of distribution (63 ml kg-1) which is consistent with the predicted plasma volume. Over the dose range 0.05-5 mg ICI D0490 kg-1, plasma levels at 2 and 24 h were linearly related to dose (r > or = 0.98) indicating that at doses up to 5 mg ICI D0490 kg-1 clearance does not appear to have a saturable component. Repeated doses of ICI D0490 (1 mg kg-1 day x 5) did not lead to drug accumulation. These studies demonstrate that ICI D0490 has excellent in vivo stability and persistence which, in conjunction with activity and toxicity data, identify ICI D0490 as a promising candidate for clinical evaluation in the treatment of colorectal cancer. PMID- 8512817 TI - Resistance to flow through tissue-isolated transplanted rat tumours located in two different sites. AB - The perfusion characteristics of the P22 carcinosarcoma were investigated in tissue-isolated tumour preparations in the ovarian and inguinal fat pads of BD9 rats. Tumours were perfused with a physiological buffer of known viscosity and changes in perfusion pressure were recorded at different perfusion rates in an ex vivo system. At perfusion pressures exceeding 30-40 mmHg tumour flow rate was directly proportional to the perfusion pressure in all tumours, indicating a constant resistance to flow. An apparent positive pressure difference across the tumour vasculature of 20-30 mmHg occurred under conditions of zero flow in either site. At low perfusion pressures, the flow resistance increased sharply due to increases in the geometric resistance of the tumours. These findings are in accord with previously published data. Geometric resistance increased with tumour volume in both sites and was approximately five times greater in the inguinal tumours than it was in the ovarian tumours, on a weight to weight basis. The dependence of tumour geometric resistance on perfusion pressure differs from the situation in normal tissues and may provide a means of manipulating the tumour microcirculation to the exclusion of the systemic blood supply. The dependence of geometric resistance on tumour site may partly explain why tumours located in different sites respond differently to various forms of therapy. PMID- 8512818 TI - Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies. AB - A trial of FAA and rIL-2 has been performed both to study the clinical efficacy of this combination and to determine whether they cause haemorrhagic necrosis by acting upon tumour vasculature. FAA and rIL-2 were given to 23 patients with progressing metastatic melanoma. FAA 4.8 gm m-2 was given as a 1 h infusion without urine alkalinisation on days 1, 8 and 15. rIL-2 (6-18 x 10(6) IU/m2/day) was given as a continuous infusion days 8-12 and 15-19 (nine patients) or days 8 12 only (14 patients). Treatment was repeated after 2 weeks unless there was disease progression. Of the 21 assessable patients there have been one complete (skin and liver) and two partial responses (skin and liver, skin and nodes) lasting 20 + 17 + and 15 months, overall response rate 14%. Unexpectedly severe hypotension after the third FAA, when given 2-4 days after RIL-2, was the major toxicity (8/15 grade 3 or 4). No alteration in coagulation parameters were seen during therapy of the first ten patients. No increase in tumour necrosis was seen in any of the 15 biopsies taken from ten patients after therapy. This suggests that FAA does not have similar vascular effects in human as it does in murine tumours. PMID- 8512819 TI - Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma. III: Cytokine studies. AB - Twelve patients undergoing IL-2 and flavone acetic acid (FAA) combination immunotherapy for advanced melanoma were studied throughout treatment for the induction of measurable levels of bioactive TNF, GM-CSF and IL-6 in their serum. This was to assess the extent of secondary cytokine induction in these patients and the possible role of such cytokines in both the toxic and therapeutic responses. The nature of the treatment schedule enabled these cytokines to be measured in response to FAA alone, FAA/IL-2 and FAA alone following IL-2/FAA activation of target cells. A small rise in the serum levels of these cytokines was seen on the initial course of FAA/IL-2 but this was minor compared to the marked elevation in levels 2-8 h following the initiation of the third course of FAA given with or without IL-2 and at a time point which coincided with maximum toxicity in those patients who experienced it. These results show that FAA alone can induce cytokine release from primed target cells. This may be associated with the therapeutic effect and/or toxicity of the agent. PMID- 8512820 TI - Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma. IV: Pharmacokinetics and toxicity of flavone acetic acid and its metabolites. AB - Flavone acetic acid (FAA) was administered at a dose of 4.8 g m-2 over 1 h to patients with advanced malignant disease in combination with Interleukin II. A new high performance liquid chromatography method is described to determine both the parent compound and eight drug-related products, and the conditions required to determine these components in plasma are discussed. The half-life over the first 8 h was 2.3 h, but the terminal clearance of the drug was extremely slow. Severe (WHO Grade 4) hypotension was observed in some patients. However, incidence of this did not appear to be associated with any differences in FAA plasma concentrations, nor were there differences in FAA clearance between those patients whose tumour responded to the drug combination and those who did not. PMID- 8512821 TI - Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. AB - There is increasing experimental evidence to suggest that expression of O6 alkylguanine-DNA-alkyltransferase (ATase) is a major factor in resistance to dacarbazine (DTIC). We recently demonstrated a progressive ATase depletion in human peripheral lymphocytes with nadir levels occurring at 4-6 h after DTIC administration (Lee et al., 1991). Therefore in an attempt to improve the clinical response rate of DTIC, fotemustine was administered 4 h after DTIC administration; since in the case of fotemustine, ATase removes the chloroethyl lesions from the O6-position of guanine, thereby preventing the formation of the cytotoxic cross-links. Sixty patients with widely metastatic melanoma received DTIC at 400, 500 or 800 mg m-2 followed by fotemustine (100 mg m-1) at 4 h after DTIC administration. Treatment was repeated every 28 days with a total of 169 cycles of chemotherapy administered; 75, 57 and 37 treatment cycles with 400, 500 and 800 mg m-2 DTIC groups respectively. Eighteen of the 60 patients responded (with three complete response); response rates were linearly related to dose, being 24%, 30% and 40% in patients receiving 400, 500 and 800 mg m-2 of DTIC respectively and the overall response rate was 30%. Median survival was 3.6 months (range, 1-15 months) with no statistically significant difference between the different DTIC treatment groups (P = 0.67). Nine patients are alive at 5 to 26 months (median 10 months); three patients with no tumour and five patients with stable disease. A statistically significant relationship was seen between the development of severe haematological toxicity (WHO > or = 3) with increasing dosage of DTIC and significant subclinical pulmonary damage was seen in 11 patients where the lung function was monitored during the course of treatment. In conclusion, it appears that with this small group of patients, escalation of DTIC dosage might not significantly affect response rates but does increase haematological toxicity. The present study provides a framework for other studies in an attempt to modulate ATase-mediated drug resistance in tumour tissues but the associated toxicity will need careful monitoring. PMID- 8512822 TI - CA 125 half-life in ovarian cancer: a multivariate survival analysis. AB - Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemotherapy was studied in 60 ovarian cancer patients and compared to known prognostic factors. Various methods reported in the literature to calculate a CA 125 half-live value were compared. Using two exponential regression models (Van der Burg et al., 1988; Buller et al., 1991), mean half-lives in stage I-II patients after complete cytoreductive surgery were respectively 10.7 days (range: 5-23) and 9.8 days (range: 7-15). Within stage III-IV patients, a significant positive correlation was seen between survival and (a) stage III (P = 0.002), (b) residual tumour < or = 1 cm (P = 0.02), (c) CA 125 normalisation after three courses (P = 0.003) and (d) CA 125 half-life < or = 20 days (P = 0.02-0.004, depending on the method used for half-life calculation). The median survival times of patients with and without a CA 125 normalisation after three courses were 27 and 14 months respectively (P = 0.003). When using the model of Buller et al. patients with a CA 125 half-life < or = 20 days had a median survival of 28 months compared to a median survival of 19 months for patients with CA 125 half lives > 20 days (P = 0.004). Half-life calculations only showed a significant correlation with survival, if pre-surgery CA 125 levels were used as a baseline. In a survival analysis using the Cox proportional hazards model, stage of disease was the most predictive variable for survival (P = 0.006). The only additional independent prognostic factor for survival was the CA 125 half-life calculated according to Buller [derived from the formula: CA 125 = exp. [i-s x (days after surgery)], in which i is the y-axis intercept and s is the slope of the CA 125 regression curve]. A CA 125 half-life < or = 20 days vs > 20 days calculated using this formula, provides an independent prognostic factor for survival in stage III-IV patients early in the course of therapy (P = 0.04). PMID- 8512823 TI - Duplex/colour Doppler sonography: measurement of changes in hepatic arterial haemodynamics following intra-arterial angiotensin II infusion. AB - Angiotensin II (AT-II) has been used to target regionally-administered cytotoxic microspheres in patients with intrahepatic tumours. The optimisation of vasoconstrictor targeting requires a knowledge of the blood flow changes induced by agents such as AT-II. We therefore assessed duplex/colour Doppler sonography (DCDS) as a means of evaluating the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with intrahepatic tumours. HABF was measured continuously in nine patients using DCDS before, during and after an infusion of AT-II (15 micrograms in 3 ml of saline over 90 s) via a hepatic artery catheter. In seven patients with less than 30% hepatic replacement by tumour, the baseline level of HABF was 331 +/- 85 ml min-1 (mean +/- s.d.), and this was reduced by 75-80% within 30 s of the start of AT-II infusion. HABF recovered rapidly from the end of the infusion, and increased by up to 20% above the baseline for approximately 2 min. In two patients with greater than 50% hepatic replacement, HABF showed no reduction but rose continuously from the start of AT-II infusion, increasing by a factor of 2-2.5 after 3-4 min. Arterial resistance showed reciprocal changes in all cases. We conclude that DCDS is effective in assessing the temporal changes in hepatic arterial blood flow caused by AT-II. In order to optimise tumour targeting, the injection of microspheres loaded with cytotoxic drugs should be completed before the end of the AT-II infusion. The targeting advantage of AT-II in patients with a high percentage hepatic replacement by tumour should be re-assessed. PMID- 8512824 TI - Interstitial photodynamic therapy. Clinical experience with diffusing fibres in the treatment of cutaneous and subcutaneous tumours. AB - Interstitial photodynamic therapy has a number of potential advantages over superficial treatment. We have treated 50 subcutaneous and cutaneous tumours interstitially, in nine patients. An additional 22 tumours in the same patients, were treated by superficial PDT. Patients received 1.5-2.0 mg kg-1 of polyhaematoporphyrin and 72 h later underwent treatment using a copper vapour dye laser producing red light at 630 nm. All interstitial treatments were delivered using cylindrical diffusing fibres and a wide range of light doses (5-1500 J cm 3). The complete response rate for all tumours treated interstitially was 52%, rising to 81% in those patients who received 2.0 mg kg-1 PHP and light doses in excess of 500 J cm-3. The overall incidence of skin necrosis was 32% and was 79% in those treated with light doses of greater than 500 J cm-3. The incidence of skin necrosis with interstitial PDT is lower than that seen with superficial photodynamic therapy but higher volumetric light doses are required to produce tumour complete responses. All treatments were well tolerated and volumes of tumour up to 60 cm3 were successfully treated. The penetration depth of 630 nm light in human breast cancer tissue was determined as 4 mm. Little true tumour tissue selectivity was detected by analysis of porphyrin levels in biopsy material. PMID- 8512825 TI - Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract. AB - The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL 2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma. PMID- 8512826 TI - Glutathione and glutathione S-transferases in Barrett's epithelium. AB - Glutathione content, enzyme activity and isoenzyme composition of glutathione S transferases were assayed in normal and Barrett's esophageal epithelium of ten patients with Barrett's esophagus. In addition, gastric and duodenal specimens from the same patients were also investigated. Glutathione content, glutathione S transferase enzyme activity as well as glutathione S-transferase pi content were all significantly lower in Barrett's epithelium as compared to normal esophageal mucosa. In contrast, glutathione S-transferase class alpha enzymes are markedly expressed in Barrett's epithelium, whereas only low amounts are present in normal esophageal epithelium. Glutathione and glutathione S-transferase composition in Barrett's epithelium show striking similarities with gastric epithelium, whereas duodenal epithelium is provided with considerable higher amounts of glutathione and glutathione S-transferases, except for levels of glutathione S-transferase class pi, which are lower. A significant negative correlation exists between glutathione S-transferase enzyme activity in the mucosa along the gastrointestinal tract, and the tumour incidence. Since glutathione and glutathione S-transferase are correlated with protection against cellular or cytogenetic damage, the low content of glutathione and glutathione S-transferases in the Barrett's esophagus may be a factor of relevance for the increased tumour risk in this tissue. PMID- 8512827 TI - Immunohistochemical expression of the mucin-type glycoprotein A-80 and prognosis in human breast cancer. AB - Immunohistochemical expression of the tumour associated mucin-type glycoprotein A 80 was investigated in a series of 173 breast cancer patients with a clinical follow-up between 13 and 19 years. A routine immunoperoxidase technique was used in formalin-fixed, paraffin-embedded surgical tumour specimens. One hundred and fifty of 173 tumours (87%) immunostained with MAb A-80. The degree of A-80 immunoreactivity was related to the tumour grade but not to lymph node status, tumour size, or nuclear DNA distribution pattern. In univariate analysis the degree of A-80 expression was found to be of significant prognostic value both in node negative and in node positive breast cancer patients (P = 0.03). Patients with non-A-80 immunoreactive tumours had significant longer distant metastases free survival times and fewer relapses than women with carcinomas composed of A 80 immunoreactive tumour cells. This prognostic value was reduced in a multivariate analysis, including lymph node status, tumour size, and nuclear DNA distribution pattern, but retained borderline significance (P = 0.08). In conclusion, the findings of this study indicate that expression of the mucin-type glycoprotein A-80 as determined by immunohistochemistry seems to be related to clinical outcome in breast cancer patients. PMID- 8512829 TI - UK Nutritional Epidemiology Group guidelines. PMID- 8512828 TI - Weekly chemotherapy in advanced prostatic cancer. AB - This randomised phase II study was performed in order to evaluate the effectiveness of a weekly chemotherapy regimen in advanced prostatic carcinoma patients (stage D2) refractory to hormonal therapy. Seventy-two cases were studied: they were randomised in a 2:1 ratio to receive either epirubicin (30 mg m-2 weekly) or doxorubicin (25 mg m-2 weekly); 48 patients received epirubicin and 24 received doxorubicin. After 12 courses of chemotherapy, the 45 evaluable patients in the epirubicin arm showed a response rate of 37.7% and the 21 evaluable patients in the doxorubicin arm showed a response rate of 33.3% (P = 0.51). Pain intensity, bone and prostatic tumour markers rapidly and significantly decreased in responders. An improvement in physical symptoms, functional conditions and in emotional well-being was observed in the majority of the treated patients. The histological analysis of bone metastases, performed before and after 12 courses of chemotherapy showed a significant reduction in neoplastic invasion and in new bone formation in responders. Cardiac performance worsened in five out of 45 patients and in ten out of 21 during the first 12 courses of epirubicin or doxorubicin respectively (P = 0.014). The median survival was 12.5 months in the epirubicin arm and 8.0 months in the doxorubicin arm (P = 0.042). Our data indicate that in advanced prostatic carcinoma, a weekly epirubicin regimen may give rapid palliative results, similar to that of doxorubicin, but with less side-effects. PMID- 8512830 TI - Histology by magnetic resonance microscopy. AB - Magnetic resonance microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 microns. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 microns. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., T1, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 micron in the near future. PMID- 8512831 TI - Proton spectroscopy in vivo. AB - 1H magnetic resonance spectroscopy (MRS) has attracted much attention in recent years. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, it is possible to perform a noninvasive chemical analysis on tissues deep within the body of a subject. Technical solutions to the elimination of water and lipid signals as well as resolution of the large number of potential metabolite peaks have been found. Most current work is on the brain, much of it in humans. This review begins with a consideration of these technical problems and also localization, editing, quantitation, and interpretation of spectra. Two diseases are considered in detail: cerebral ischemia (including stroke and neonatal ischemic/hypoxic injury) and cancer; a further section briefly reviews studies on other diseases. In the immediate future, 1H MRS is likely to benefit from a number of technical advances: higher field magnets, better control of gradients and eddy currents, more sophisticated radiofrequency (RF) pulses, and 1H-observe/13C-edited spectroscopy all offer potential improvements. Another major improvement will come from increased user-friendliness of clinical spectrometers and use of automated objective methods for spectroscopic data analysis. PMID- 8512833 TI - Education: footing the bill. PMID- 8512832 TI - Nursing abroad: a place of extremes. PMID- 8512834 TI - Nurses work. The good employers' pledge. PMID- 8512835 TI - Nurses work. The human cost. PMID- 8512836 TI - Seclusion practice in psychiatric nursing. AB - The report of the Ashworth Inquiry (1), which was jointly commissioned by the Special Hospitals Service Authority and the Secretary of State for Health, recommended the phasing-out and the ultimate ending of seclusion at Ashworth Hospital. The Special Hospitals Service Authority's response was that, although it intends to reduce the use of seclusion to a minimum, it was unable to support its total abolition. This has once again brought into question the practice of seclusion in the treatment of psychiatric patients. This article examines the literature surrounding seclusion practice and some of the alternatives in dealing with severely disturbed and violent psychiatric patients. PMID- 8512837 TI - Securing methods for peripheral cannulae. AB - The use of a sterile transparent dressing (Venigard, Consolidated Medical Equipment, London) was compared to the use of a non-sterile tape (Mefix, Molnlycke, Sweden) for securing peripheral cannulae in paediatric patients. Children from all medical specialties were prospectively randomised into one of two groups. The failure of a cannula (defined as the removal of the cannula before treatment was completed) was plotted against duration in each of the two groups. Statistical tests (life table analysis) suggested no significant difference (p = > 0.05). The authors conclude that the use of a sterile transparent dressing secures peripheral cannula as effectively as non-sterile tape. PMID- 8512838 TI - Student evaluations of nurse teachers. AB - Nurse teachers are accustomed to having their performance regularly appraised by their colleagues, but what about appraisal by students? Although this idea may seem alien to some, it has been in operation in the United States and Canada for some years. The author obtained a scholarship from the United Kingdom Directors of Nurse Education Group and visited the University of Texas in Austin to discover how the system operates. Her impressions were favourable, but on return to the UK she found hesitancy and doubt among her colleagues. This article describes her findings in Texas and outlines why she feels the system would be of benefit in the UK. PMID- 8512839 TI - Ethics: working with the stories nurses tell. AB - Story-telling may have been overlooked as an educational and therapeutic technique in nursing's drive for scientific excellence. In the first of two articles, the authors explain how their interest in storytelling as a tool for nurses was kindled, and how they have developed the method of encouraging nurses to write and tell stories of their own experience in an attempt to come to terms with some of the ethical and moral issues they face. Next week, an example of a story written by a nurse is given. PMID- 8512840 TI - Overpowering empowerment. PMID- 8512841 TI - Information technology: the ultimate notepad. PMID- 8512842 TI - Professionalism: the empirical new clothes. PMID- 8512843 TI - HIV/AIDS: evaluating the risks. PMID- 8512844 TI - Medical aid: health care afloat. Interview by Rael Martell. PMID- 8512845 TI - Purchasing: buying in good faith. PMID- 8512846 TI - Community care reforms: health and housing. PMID- 8512847 TI - Good practice code for colleges and schools of nursing and midwifery. PMID- 8512848 TI - Nurses work. A new careers convention. PMID- 8512849 TI - Nurses work. No students--no future. PMID- 8512850 TI - Employing transplant recipients: a pilot study. AB - This pilot study aimed to give some indication of the reasons why many transplant recipients seem to have difficulty finding employment. Twenty-one transplant recipients and 17 employers completed a questionnaire covering a variety of health and employment-related topics. The transplant procedures the recipients had undergone included heart, heart/lung, heart/liver, and heart/kidney. The employers represented a selection of large and small companies drawn from the Standard Occupation Classification. The responses indicated that the employers' knowledge of transplantation varied according to size of the company, the nature of its work and which department had completed the questionnaire (occupational health or personnel). The views of recipients on employment prospects varied, with some claiming they had not attempted to find employment as they were happy with their new health and 'just enjoyed living', while others considered employment an important factor in the quality of their lives. Key indicators for future research efforts have been identified. PMID- 8512851 TI - Ethics: how nurses can use a story-telling approach. AB - In the second of two articles on the value of story-telling, the authors show how writing down her story helped one nurse come to terms with a traumatic incident that had occurred some 16 years earlier, and how her story acted as a catalyst for the creative imaginings of a group of nurses at a workshop. PMID- 8512852 TI - Co-ordinating an orthopaedic service. AB - Fractured neck of femur is an injury commonly sustained by elderly people. The subsequent needs of this patient group are complex and diverse, and may not be met within the competencies of standard orthopaedic units. In an attempt to overcome this deficiency, Frenchay Hospital introduced the role of clinical orthopaedic co-ordinator to assist in the successful liaison between orthopaedic, elderly care and community services. The author reports on the venture's success. PMID- 8512853 TI - Research and destroy. PMID- 8512854 TI - Blanded by science. PMID- 8512855 TI - Sister Susie. The name game initiative. PMID- 8512857 TI - Information technology: double your disk memory. PMID- 8512856 TI - Care of the elderly: incontinence through incompetence. PMID- 8512858 TI - Health care worker infected with HIV. PMID- 8512859 TI - Publicity over HIV-positive health workers. PMID- 8512860 TI - School nurses need support, training and resources in educating children about HIV and AIDS. PMID- 8512861 TI - Beverley Allitt: in the wake of Allit. PMID- 8512862 TI - Legal issues: implications for the future. PMID- 8512863 TI - Nursing in Canada: evolution and opportunity. PMID- 8512864 TI - Effects of change on sisters/charge nurses. PMID- 8512865 TI - Setting the scene for experiential learning. PMID- 8512866 TI - Peripheral i.v. therapy (continuing education credit). PMID- 8512867 TI - Tomlinson: a social policy perspective (Part 2). AB - This article is the second of two which explore the Tomlinson Report and its implications from a social policy perspective using a "policy as process" model. In this article, the main points of the report and the government's response to it will be analysed with reference to areas of particular interest to nurses and nursing, that is, primary and community health services, the acute sector, nurse education, and research. The impact on nursing and health policy, both in London and the United Kingdom, will also be discussed. PMID- 8512868 TI - Workwise: a job problem shared. PMID- 8512869 TI - Freedom up in smoke. PMID- 8512870 TI - Sister Susie. New nurses act up. PMID- 8512871 TI - Nurses' pay: get the bucket and mop, nurse. PMID- 8512872 TI - HIV-positive nurse goes to ground. PMID- 8512873 TI - Limb loss in surgical practice. PMID- 8512874 TI - Significance of chronic duodenitis. PMID- 8512875 TI - Compliance by cerebral palsy (CP) patients attending a child neurology service, in a developing country: a preliminary study. AB - In an attempt to determine the extent to which cerebral palsy patients complied with doctors' recommendations, by regularly attending the follow-up clinics of the Paediatric Neurology Unit of the University of Nigeria Teaching Hospital (UNTH) Enugu, the records of the CP patients seen in the Unit during three years (1985-1987) were scrutinized. A very high default rate of over 88% was noted. Of the 155 CP patients registered during the period, only 18 were still attending the clinic by the end of 1988, the follow-up period ranging from 12 to 47 months. Default from follow-up correlated significantly with the socio-economic status of the patients. There was no correlation between compliance and the type of CP, or the presence of other concurrent neurological disorders. It is thought that early recognition of factors that are associated with poor compliance is important. It will result in early identification of the group at risk for default, and in efforts being made to give them the support and advice that will enable them to benefit fully from the available services. PMID- 8512876 TI - Viral pathogens of acute lower respiratory infections in pre-school Nigerian children and clinical implications of multiple microbial identifications. AB - In a prospective study of acute lower respiratory infections (ALRI), at the University College Hospital, UCH, Ibadan, 35 viral pathogens were identified by immunofluorescence (IF) techniques from 24 (68.6%) respiratory specimens from 35 hospitalised pre-school children. The respiratory diagnoses comprised croup, bronchiolitis, pneumonia and pleural effusion. The viral identifications comprised 14 (40.0%) of parainfluenza virus type 3, 10 (28.6%) of respiratory syncytial virus (RSV), 5 (14.3%) of influenza virus type A, 4 (11.4%) of parainfluenza virus type 1 and 2 (5.7%) of influenza virus type B. Two or more viral agents were identified in as many as 10 (41.7%) of the 24 IF positive secretions, 8 (80.0%) of which were obtained from children with features of protein energy malnutrition. Twenty subjects had both virological and bacteriological analyses, in 8 (40.0%) of whom co-existing bacteraemia was identified. Four (50.0%) of these blood culture positive subjects, also had features of overt malnutrition. Neither the age nor the sex was significantly related to the viral identifications (P > 0.81 & 0.35 respectively). Similarly, the final respiratory diagnoses were not significantly related to the viral identifications despite the seemingly suggestive relationship between a diagnosis of croup and parainfluenza identifications as well as that between pneumonia and RSV/parainfluenza type 3 identifications. It is concluded that the high proportion of positive viral identifications is a pointer to the importance of viruses as possible primary etiological agents of ALRI in countries of the West African sub-region and perhaps in developing countries of other tropical subregions. The multiplicity of microbial identifications (viruses and bacteria), seen in malnourished children, may explain the clinical severity of ALRI in the same group of children. The usefulness of IF as a rapid diagnostic tool, as well as the potential implications of our findings on ARI control in developing countries, are discussed. PMID- 8512877 TI - Amputation of the lower limb in Korle-Bu Teaching Hospital, Accra. AB - With the increasing life expectancy of our population, peripheral vascular disease will soon become a major problem in our society. The incidence of neoplasia affecting the lower limbs is reported to be on the increase in Africa. The increased activity of our herbal colleagues has brought in its wake large numbers of patients with disastrous complications of cellulitis. The lack of sophisticated methods of diagnosis and treatment coupled with the ignorance of our people and late presentation mean that many limbs that could be salvaged will continue to be lost. We, as health workers, can lessen the emotional and social burden of these unfortunate patients by ensuring their early and rapid integration back into their communities. PMID- 8512878 TI - Asymptomatic significant bacteriuria among pregnant and non-pregnant women in Sagamu, Nigeria. AB - In a study carried out among 510 pregnant and 304 non-pregnant women at Ogun State University Teaching Hospital, Sagamu, 122 (23.9%) of the pregnant women and 37 (12.2%) of the non-pregnant women had significant bacteriuria. The rate amongst the pregnant women was significantly higher than in non-pregnant women (P < 0.001). There was a correlation between pyuria and significant bacteriuria in 45 (8.8%) of the pregnant women and in 11 (3.6%) of the non-pregnant women. Significant bacteriuria was closely associated with nulliparae. Most of the pregnant women with significant bacteriuria belonged to the low socioeconomic group. Unlike in previous studies in this country, the most prevalent organism in this study was the Staphylococcus aureus. In view of the high incidence of the problem in this environment, it is important that routine screening of urine for significant bacteriuria should be part of our ante-natal clinic services at least on the first visit of pregnant women to ante-natal clinics. PMID- 8512879 TI - Mortality in infants of birthweight 2500g and above: a hospital-based review in Port Harcourt, Nigeria. AB - In order to study mortality patterns among full-grown infants, the records of all babies of birthweight 2500g and above admitted into the Special Care Baby Unit of the University of Port Harcourt Teaching Hospital, Nigeria, over a three-year period were retrieved and examined. There was a total of 1519 admissions during the period, 878 (58%) of whom weighed 2500g and above, and 39 of these full-grown babies died. Common associated findings among infants who died were birth asphyxia and congenital malformations. Furthermore birth asphyxia occurred more commonly among the large and mature babies and was a significant cause of first week deaths. It should be possible to reduce the magnitude of wastage of this group of babies by encouraging pregnant women to make use of the available facilities. High risk pregnancies should be recognised promptly and above all there should be intimate cooperation among all those involved in delivery and care of the newborn; paediatricians, midwives, obstetricians and anaesthetists. PMID- 8512880 TI - Seasonal characteristics of malaria infection in under-five children of a rural community in southern Ghana. AB - In a quarterly survey of malaria infection in the under-five children conducted at Gomoa Onyadze/Otsew Jukwa, a rural community in the Central Region of Ghana from December, 1986 to September, 1987, crude parasite rates ranged from 19.6 to 33.5 per cent in the dry season (December and March) and 33.0 to 44.0 per cent in the wet season (June and September). P. falciparum was the predominant parasite species by parasite formula analysis with higher rates in the rainy season (94.2 to 95.8 per cent) compared to that of the dry season (51.4 to 78.8 per cent). P. malariae (20.4 per cent), P. ovale (2.7 per cent) and mixed infection rates were higher in the dry season (December and March). As high as 30.4 to 44.8 per cent of positive parasite slides had parasite density of above 3200 per microliter of blood (above class 6 degree of parasitaemia). Depending on the season 7.2-27.3 per cent of children had parasite density above 25,600 per microliter of blood (above class 10 degree of parasitaemia). PMID- 8512881 TI - 2% plain xylocaine for subarachnoid or spinal anaesthesia. AB - 56 males and 14 females undergoing various lower abdominal and lower limb surgery were given Spinal Anaesthesia using 2% Plain Xylocaine. The different volumes used were 3.0ml, 3.5ml and 4.0ml. The levels of analgesia achieved were adequate for the surgery. There was no significant difference between the 3 volumes in the mean levels of analgesia obtained and the mean duration of sensory and motor blockade. This study has confirmed the usefulness of 2% Plain Xylocaine in Spinal Anaesthesia. PMID- 8512882 TI - Is schizophrenia a preventable disease? AB - Schizophrenia is a fairly common disease, afflicting about one per cent of the adult population. It is one of the most severe illnesses that afflict humans and it often runs a chronic, debilitating course. Various lines of evidence now show that the illness is a disease of the brain even though there is no single neuropathological sign off the illness that is common in all patients. Heredity remains the single most important etiological factor associated with the illness. However, even though strong, its link with the illness lives room for the inference that environmental factors are also involved. Intrauterine viral infection and perinatal birth complications are two of such putative environmental etiological factors. The present stage of genetic engineering does not permit for a vigorous campaign of primary preventive measures for schizophrenia even though the prospects are bright that this may soon be so. Secondary prevention is an eminently effective measure for an overwhelming majority of the patients. Tertiary measures are necessary for a substantial minority and, when delivered by highly trained personnel, can improve the quality of life for those that would otherwise develop incapacitating personality and intellectual deterioration. PMID- 8512883 TI - Unusual oesophageal cancer: a report of four cases. AB - The prognosis for carcinoma of the oesophagus is generally dismal especially when patients present late. Any clues to early diagnosis and management and identification of rapidly progressive variants are therefore helpful. Reports and review of the literature are presented with respect to four unusual cases of oesophageal carcinoma treated in the University of Ilorin Teaching Hospital in 1985 and 1986. Four men aged 59, 60, 55 and 60 years respectively presented with multiple polypoid carcinoma of the oesophagus, malignant oesophago-bronchial fistula at the level of the left main stem bronchus, achalasia co-existing with oesophago-gastric carcinoma and a small focus of carcinoma of the distal thoracic oesophagus presenting with widespread thoracic metastases and malignant pleural effusion mimicking advanced bronchogenic carcinoma. The unusual clinico pathological features with the autopsy findings in the last case can influence diagnosis, management and prognosis of oesophageal cancer in general and of such cancer associated with pre-malignant conditions like achalasia and oesophageal polyps in particular. PMID- 8512884 TI - Antagonism of drug therapy for hypertension by nonsteroidal antiinflammatory drugs. AB - Three cases, in which the deterioration of blood pressure control was associated with the onset of therapy with nonsteroidal anti-inflammatory drugs (NSAIDS), are reported. It is suggested that this effect of the NSAIDs could possibly have resulted from the inhibition of the biosynthesis of the prostaglandins, some of which have vasodilatory or natriuretic properties. This interaction, hitherto unreported from our environment and therefore not commonly recognised, is of relevance in the drug treatment of hypertension since the widely used NSAIDs have the potential to impair the effectiveness of several antihypertensive drugs. It should be taken cognizance of when using both antihypertensive drugs and NSAIDs in any hypertensive patient. PMID- 8512885 TI - Structural and in vivo mechanical characterization of canine patellar cartilage: a closed chondromalacia patellae model. AB - The purpose of this project was to study the relationship between the structure of the patellar cartilage and its response to static compressive loading with a closed chondromalacia patellae model. An animal model was used to induce degeneration of the patella that was monitored quantitatively and qualitatively as a function of time. Ten adult mongrel dogs had their left patellofemoral groove replaced by a customized metallic implant covered with a thin film of polyethylene for periods of 3 months (five dogs) and 6 months (five dogs). An indenter was designed to perform mechanical indentation testing on the patellar cartilage in situ. The animals were anesthetized and the response of patellar cartilage to a static compressive load of 4.5 MPa was monitored for 20 min and its relaxation after load removal for 20 min. Indentation tests were performed every 3 months of the implantation period. At the end of the implantation period, the patellae were processed for histology, and sections were stained with Safranin-O indicative of the proteoglycans content. Macroscopically, no apparent degeneration or fibrillation of the patellar surfaces was observed after 3 or 6 months of implantation. However, the patellar surface showed a change in coloration after 6 months. A 17 +/- 3% and 37 +/- 8% deformation of the cartilage were calculated for the 3-month and 6-month specimens, respectively. Histologically, a progressive loss of proteoglycans was observed in the matrix as a function of implantation time. These results indicated that an increase in cartilage compliance is associated with an intrinsic remodeling of the cartilage matrix and that these changes might occur without external signs of degeneration and can be quantified. PMID- 8512886 TI - Brain injury causes loss of cardiovascular response to hemorrhagic shock. AB - The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective. PMID- 8512887 TI - Long-term evaluation of prosthetic mitral valves in sheep. AB - We have developed an in vivo model for chronic evaluation of prosthetic heart valves using juvenile domestic sheep. This report summarizes the results of a study conducted to assess a new bileaflet prosthetic valve. Nine juvenile sheep underwent mitral valve replacement using standard cardiopulmonary bypass techniques including mild hemodilution, systemic hypothermia, and cold fibrillatory arrest. The average time on cardiopulmonary bypass was 57 min. There were no surgical or anesthetic complications. Two (22%) early deaths occurred due to prosthetic annular size disproportion (1) and preexisting pneumonitis (1); postmortem examination of both implanted devices revealed normal function. The remaining seven animals (78%) remained clinically well and underwent left and right heart catheterization, angiography, and sacrifice after the 150th postoperative day. Left ventriculograms demonstrated normal valve function in all cases. The average mitral transvalvular gradient, as determined by simultaneous pulmonary capillary wedge and left ventricular and diastolic pressure, was 5.4 mm Hg. Thus we have developed a new in vivo model that provides a successful model for chronic evaluation of prosthetic valves using a sheep model. There are several features contributing to the success of our model. First, to decrease the possibility of bacteremia and seeding of the prosthesis, a single incision is used and intraoperative monitoring lines minimized. Second, we use a short cardiopulmonary bypass run (range 52-62 min), with no period of ischemia. Third, fresh sheep blood is transfused immediately following bypass to prevent anemia. Fourth, gastric decompression is used to prevent ruminal bloating, with the resulting vena caval compression that decreases blood return while on bypass. PMID- 8512888 TI - A porcine model of hyperdynamic endotoxemia: pattern of respiratory, macrocirculatory, and regional blood flow changes. AB - Systemic sepsis and multiple organ failure are frequent and often fatal complications after major surgery and trauma. In contrast to the biphasic hemodynamic pattern characteristically seen in patients, most experimental animal models have failed to reproduce the early, hyperdynamic phase of sepsis and endotoxemia. We have designed a standardized model of endotoxemia, which is elicited by continuous IV infusion of Salmonella abortus equi endotoxin in anesthetized juvenile pigs (age 8-12 weeks). The plasma concentration of endotoxin--as evaluated by the LAL test--is significantly elevated within less than half an hour following the start of endotoxin administration and is accompanied by a rapid fall of the leukocyte count in peripheral blood. High cardiac output and low systemic vascular resistance reflect a hypercirculatory state, during which left ventricular filling pressure is maintained by carefully monitored volume substitution (6% dextran 60). In the present investigation, different doses of endotoxin (3.8 and 11.4 micrograms/kg, respectively) were infused intravenously and investigated for their effect on respiratory, macrocirculatory, and regional blood flow alterations. The development of respiratory deterioration depended on the duration of endotoxin administration and on the height of endotoxin plasma levels. In all animals, a high cardiac output was maintained throughout 3.5 hr of endotoxemia. Regional blood flow to the myocardium and liver increased, whereas blood flow to the gastrointestinal tract and the spleen was compromised without difference between both groups. It is concluded that this porcine model should provide the potential for further insight into the early pathophysiological mechanisms involved in the development of multiple organ failure in patients with sepsis and endotoxemia. PMID- 8512889 TI - Replacement of the cervical and thoracic esophagus in dog using free jejunal autografts. AB - Free revascularized jejunal grafts based on a single branch of the mesenteric artery and vein were selected and used for replacement of the cervical esophagus in 20 dogs. The graft pedicle was transplanted to the left external jugular vein and the internal carotid artery using end-to-side microvascular anastomoses. The procedure was successful in all the dogs; however, five dogs had fistula formation that healed spontaneously. A similar jejunal autograft was used to replace the thoracic esophagus in 20 dogs. The recipient vessels were the internal thoracic artery and vein. Only four dogs survived. Thirteen dogs could not survive because of infection resulting from leakage of esophageal content from the esophagojejunal anastomoses into the thoracic cavity. Only two dogs had infarcted jejunal grafts. The four surviving dogs could swallow liquid and semisolid food but they never returned to solid food because of difficulties with swallowing. Graft survival was confirmed with endoscopy and arterial angiography. Narrowed jejunal graft lumen was apparent with contrast radiography and endoscopy. The jejunal grafts kept peristalsis and contracted in coordinated fashion with the proximal esophagus. At necropsy, wound healing was evaluated using bursting strength and bursting circular wall tension. Although slight adhesion and fibrosis around the grafts as well as slight inflammatory reaction around the suture material were observed, the jejunal grafts were grossly and microscopically normal. All esophagojejunal anastomoses healed and the jejunal mucosa looked normal. PMID- 8512890 TI - Diagnosis of intestinal ischemia in the rat using magnetic resonance imaging. AB - Noninvasive diagnosis of persistent ischemia after intestinal revascularization has remained an elusive goal. Because magnetic resonance imaging (MRI) can detect changes in tissue water, we studied its efficacy in differentiating ischemic from perfused intestine in an animal model. Six-week-old rats were subjected to (1) 30 min superior mesenteric artery (SMA) occlusion and reperfusion, (2) permanent SMA ligation, or (3) sham operation, and were then imaged for 90 min using a small animal MRI scanner with T1 weighting (TR = 1000 msec, TE = 25 msec). In an additional group of rats, the experiment was repeated using a new contrast technique consisting of oral ferrite to decrease luminal signal and intravenous gadolinium to increase bowel wall signal. Mean abdominal intensity over the scanning period was calculated for each animal (n = 5 rats per experimental group). Definition of individual bowel loops was subjectively improved in animals scanned with intravenous and oral contrast. Mean abdominal intensity was significantly lower in ligated vs sham rats (43.90 +/- 8 vs 59.63 +/- 6 and 46.19 +/- 6 vs 54.26 +/- 6, with and without contrast, respectively). There was no significant difference in intensity between reperfused and sham animals. MRI differentiated persistently ischemic bowel from viable bowel in this model, both with and without the use of contrast. These data suggest that MRI may have a potential role in the noninvasive diagnosis of persistent intestinal ischemia. PMID- 8512891 TI - Limited survival of rat small bowel transplants preserved in University of Wisconsin solution for 48 hours. AB - We have previously shown that rat small bowel may successfully be transplanted after preservation for 24 hours. In this study, syngeneic rat small bowel transplants were studied by light microscopy and transmission electron microscopy during and after preservation in University of Wisconsin (UW) solution for 48 hours. A total of 6 transplants were carried out using a previously described, standardized technique. In most cases, the bowel appeared histologically well preserved at the end of the 48 hr storage period (prior to implantation). Upon revascularization, however, reperfusion injury was dramatic, with loss of villi and crypts and inflammatory cells in all layers. The bowel was abnormal grossly as well as microscopically. This injury was irreversible with persistently abnormal histology for up to 1 week in all but 2 cases. We conclude that UW solution alone may allow satisfactory preservation of intestinal grafts for 48 hours only in isolated cases, and is therefore not adequate for predictable, satisfactory 48 hr preservation. Attempts to prevent reperfusion injury with oxygen-free radical scavengers are in progress. PMID- 8512892 TI - Linea alba closure: determination of ideal distance between sutures. AB - An experiment was conducted to determine the optimal distance between sutures in closure of abdominal midline incisions. Human cadaveric fascia was harvested soon after death and stored at -70 degrees C until testing. Suture pullout tests were performed to determine the maximal force applied to the fascia before pullout. Fascia from the opposite side of the same cadaver was used as a control. In a first series of testing, we observed that the pullout force of two sutures dropped linearly as they were brought closer than 12 mm apart. In a second series we observed no increase in pullout force using multiple sutures closer together compared to fewer sutures 15 mm apart. The experiments suggest that the mechanical requirements of closing a midline abdominal incision are met by placing sutures 10-15 mm apart. PMID- 8512894 TI - Morphologic descriptions of Taenia asiatica sp. n. AB - Among taeniid tapeworms infecting humans through pork or beef, Taenia solium Linnaeus 1758 and Taenia saginata Goeze 1782 have already been known. Based on the morphologic characteristics of adult and metacestodes of Asian Taenia saginata, the third kind of human taeniid tapeworm known to distribute in Asian countries, a new species name of Taenia asiatica is proposed. In addition to the known biology in their intermediate hosts, T. asiatica was different morphologically from Taenia saginata Goeze 1782 in having the unarmed rostellum on the scolex of adult, the large number of 'uterine twigs' and the existence of 'posterior protuberance'. These structures in the gravid proglottids were used as taxonomic keys in taeniid tapeworms for the first time. T. asiatica metacestode (Cysticercus viscerotropica) was different morphologically from T. saginata metacestode (Cysticercus bovis) in having wartlike formations on the external surface of the bladder wall. PMID- 8512893 TI - Intraoperative assessment of bowel viability. AB - Viability of ischemic bowel was assessed in 30 dogs after mesenteric arterial ligation in a 40-cm length of ileum. Viability was evaluated using two gross features, color and peristalsis, and four objective methods including bowel wall surface oximetry (pO2), Doppler ultrasound, quantitative fluorescein fluorimetry, and myoelectric activity measured by a strain gauge probe. Each parameter was measured at 2-cm intervals within the 40-cm ischemic segment before resection and anastomosis was performed. There were seven fatal anastomotic leaks, all due to further bowel necrosis. Survival did not correlate with bowel color, presence of peristalsis, bowel wall pO2 Doppler ultrasound, or the myoelectric parameters. However, fluorescein fluorimetry was predictive of long-term viability. These results suggest that quantitative fluorescein fluorimetry may be a useful adjunct in intraoperative bowel viability assessment. PMID- 8512895 TI - Secretions of the biliary mucosa in experimental clonorchiasis. AB - The histological change of the biliary mucosa in clonorchiasis is characterized as adenomatous hyperplasia, and cross-sectioned mucosa looks like intestinal mucosa. In addition to the glandular hyperplasia, the metaplasia of mucin secreting cells is also known. The present study investigated the presence of intestinal secretion from the biliary mucosal cells of rabbits and rats with Clonorchis sinensis infection. The rabbit was infected with 300 and the rat was infected with 100 metacercariae of C. sinensis. A part of the animals were followed up after praziquantel treatment. The rabbit livers were prepared for histochemistry to observe any endocrine secretion and the bile duct mucosa of the mice was processed for the activity of brush border membrane (BBM)-bound enzymes of the small intestine. Immunohistochemistry with the polyclonal antibodies and biotin-streptavidin-peroxidase staining kit showed no positive cells for gastrin and secretin, but a few cells were positive for serotonin. The proliferated biliary mucosa of the mice revealed no activity of disaccharidases and aminopeptidase. Only alkaline phosphatase activity was found both in the control and the infected. The hyperplastic biliary mucosal cells showed no gastrointestinal secretory functions. The serotonin secreting cells may be one of the inflammatory cells. PMID- 8512896 TI - [Effects of interferon-gamma in T cell subsets of mice infected with Toxoplasma gondii]. AB - This study was performed to evaluate differences of T cell subsets according to the injection period of recombinant mouse interferon-gamma (IFN-gamma) in acute Toxoplasma gondii infection. Each mouse was infected intraperitoneally with 100 cysts of Beverley strain T. gondii, and injected with 5 x 10(4) units of IFN gamma every other day two tmres. The percentage of Thy-1,2 cells and L3T4/Ly-2 cell ratio were significantly increased in the mice that received two doses of IFN-gamma on days 2 and 0 before infection, or days 0 and 2 after infection. The percentage of Ly-2 cells decreased in the IFN-gamma injected groups at the 3rd and 4th week after infection. The results suggest that administration of IFN gamma to T. gondii-infected mice improves the changed population of T cell subsets to a normal state, especially when IFN-gamma was injected just after the infection. PMID- 8512897 TI - [Identification of surface antigens of Trichomonas vaginalis]. AB - Surface proteins of Trichomonas vaginalis (T. vaginalis) were analyzed to study the antigenic variation. The surface proteins of protozoa were labelled by N hydroxysuccinimide-biotin (NHS-biotin), the NHS-biotin-labelled proteins were immunoprecipitated with rabbit antiserum to purify the antigenic fractions and analysed by SDS-PAGE plus electroblotting. The results obtained in this study were as follows; Biotinylated T. vaginalis-proteins obtained from intact cell and cells disrupted prior to labelling were detected by anti-biotin-peroxidase in Western blots. Labelled proteins were immunoprecipitated by T. vaginalis immunized rabbit serum and the six bands with the molecular weights of 46, 60, 68, 90, 130 and 220 kDa were identified as having antigenicity. T. vaginalis HY 1, HY-15 and ATCC 50148 were immunoprecipitated by immune rabbit serum after biotinylation and there were no difference from antigenic bands among these strains by this technique. In conclusion with the results obtained in the present study, it was assumed that surface proteins of T. vaginalis were labelled by biotinylation and the six labelled bands at 46, 60, 68, 90, 130 and 220 kDa in their molecular weight were identified as having antigenicity by immunoprecipitation (IP) and this biotinylation-IP technique may be used for further study of surface antigen of T. vaginalis. PMID- 8512898 TI - Antigenic protein fractions of Metagonimus yokogawai reacting with patient sera. AB - Antibody test is sometimes necessary for the diagnosis of acute human metagonimiasis because eggs may not be detected in stool. The antibody test (ELISA) was evaluated for its significance by reacting human sera from clinically diagnosed metagonimiasis, fascioliasis, clonorchiasis and paragonimiasis with 4 crude extracts of Metagonimus yokogawai (metacercariae), adults of Fasciola hepatica, Clonorchis sinensis and Paragonimus westermani. By ELISA, 10 of 11 metagonimiasis sera showed the highest absorbance (abs.) to the homologous antigen. Cross reactions to M. yokogawai antigen occurred most frequently in clonorchiasis sera. The antigenic protein fractions in M. yokogawai metacercarial extract were observed by SDS-PAGE/immunoblot using patients and control sera together with experimental cat sera. Out of 14 protein bands in the extract, 11 bands were reacting. Cross reacting bands to other trematodiasis sera were frequently observed. Of the reacting bands, 66 and 22 kDa proteins were recognized as specific for metagonimiasis. PMID- 8512899 TI - Applicability of ABC-ELISA and protein A-ELISA in serological diagnosis of cysticercosis. AB - Specific antibody test in serum and cerebrospinal fluid (CSF) is still the main mode of serological diagnosis of cysticercosis. Of different techniques of antibody test, enzyme-linked immunosorbent assay (micro-ELISA) has widely been applied. This study was undertaken to observe whether diagnostic capability can be improved by applying more sensitive techniques such as Protein A-ELISA and avidin biotin complex ELISA (ABC-ELISA). When evaluated using 115 sera of human cysticercosis, the antibody positive rates were not significantly improved in Protein A-ELISA (82.6%) and in ABC-ELISA (86.1%) than in micro-ELISA (81.7%). The specificities, evaluated in 165 sera from other diseases and normal controls, were significantly improved (88.5% by micro-ELISA, 93.3% by Protein A-ELISA and 93.8% by ABC-ELISA). Antibody levels (absorbance, abs.) in individual serum were correlated well (r = 0.83-0.86) each other. An actual benefit of Protein A-ELISA and ABC-ELISA was that they needed smaller amount of test sample. PMID- 8512900 TI - Efficacy of fumagillin against Thelohanellus kitauei infection of Israel carp, Cyprinus carpio nudus. AB - The potential of fumagillin dicyclohexylamine salt to treat and prevent intestinal giant-cystic disease in Israel carp, Cyprinus carpio nudus, was monitored in field experimental studies. In experiment 1 (therapeutic), most fish were already naturally infected with more advanced stage of Thelohanellus kitauei. Fumagillin was administered to fish (mean body weight of 830 g) for a period of one month at a dose of 10.62 mg in the first group and 5.3 mg in the second group per fish per day. In experiment 2 (prophylactic), most fish also were already naturally infected with an early developmental stage of the protozoa and fish (average body weight of 484 g) were administered fumagillin for 45 days at a dose of 3.95 mg per fish per day. In both experiments, the cumulative mortalities of fish and the extrusion rates of the polar filaments of the spores were significantly decreased in a dose-independent fashion. In experiment 2 no dead fish were observed. No adverse side effects of the drug were observed among fish from any dosage group. In experiment 2, an oval or dot-like concave lesion of most cysts developed at the 7th day and the vegetative form was never observed at the 17th day postmedication and the cysts were grossly reduced in size as compared with the control group, beginning at the 24th day until the end of the study. In contrast, it was scarcely effective to the cysts in experiment 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512901 TI - Prevalence of head louse infestation in primary school children in Kangwon-do, Korea. AB - We tried to reveal the prevalence rates of the head louse infestation in school children in Kangwon-do, Korea in December 1990. A total of 912 children in four primary schools was examined. The positive rate for adults and/or nits of Pediculus humanus capitis was 37.2%. One school was followed-up without specific intervention. There was no significant change of the prevalence rate 6 months after the first examination from 66.0% to 57.3%. We could see the persistent infestation rate if there was no intervention. We are emphasizing the significance of worm positive rate because it represents the potentiality of active transmission. PMID- 8512902 TI - Parvatrema timondavidi (Digenea; Gymnophallidae) transmitted by a clam, Tapes philippinarum, in Korea. AB - Metacercariae of Parvatrema timondavidi (Digenea; Gymnophallidae) were found from Tapes philippinarum, one of the most common marine clams in Korea. T. philippinarum was collected from a fishery market in Seoul, and all of the clams examined were found to contain many gymnophallid metacercariae. To get adult worms, 10 ICR mice were fed with 100 metacercariae each and sacrificed by cervical dislocation at 7, 10 and 14 days after the infection. The adult worms harvested from the intestinal contents of the mice were morphologically characterized by oval body shape, large oral sucker with lateral projections on the lip, absence of the ventral pit, single cluster of vitellaria, and separately located genital pore from the ventral sucker. Based on these characters they identified as P. timondavidi Bartoli, 1964. This study first confirms the presence of P. timondavidi metacercariae in T. philippinarum in Korea. PMID- 8512903 TI - A case of biliary ascariasis accompanied by cholelithiasis. AB - A 43-year-old Korean woman with biliary ascariasis accompanied by cholelithiasis is reported. Her chief complaints were abdominal pain, nausea, and vomiting. She had the past history of several attacks of abdominal pain in her childhood. Biliary stones were recovered from the left hepatic duct after cholecystectomy, which contained degenerated cuticle or body wall, and numerous eggs of Ascaris lumbricoides. It is strongly suggested that the biliary stones were formed from the dead Ascaris worm(s). This is a rare case of biliary ascariasis during the recent 5 years in Korea. PMID- 8512904 TI - Whither the treatment for the TMJ? PMID- 8512905 TI - Comparison of arthrotomographic and magnetic resonance images of 50 temporomandibular joints with operative findings. AB - Arthrotomography and magnetic resonance imaging (MRI) were carried out on 50 temporomandibular joints (TMJs) in 48 patients who were being considered for surgery for clinically diagnosed internal derangement. The patients presented over a 4-year period with pain and dysfunction which had failed to respond to conservative management. Open surgery was carried out on all TMJs and operative findings compared with the results of imaging. The clinical diagnosis of internal derangement was confirmed in every case by imaging and at surgery. Arthrotomography over-diagnosed non-reducibility of an anteriorly displaced meniscus and perforation. MRI over-diagnosed non-reducibility to a lesser extent and under-diagnosed perforation. MRI demonstrated neither bony changes nor adhesions. Dynamic arthrotomography produced the best images of meniscal derangement in function and the pre-arthrogram tomograms were the best indicator of osseous abnormality. Arthrotomography was the preferred imaging technique. PMID- 8512906 TI - A retrospective study of 66 titanium cranioplasties. AB - A review was undertaken to assess the outcome of treatment in 66 patients for whom a titanium prosthesis was provided for the repair of a calvarium defect. While many aspects were satisfactory, certain disappointing features led to a prospective pilot study which enabled the following problems to be identified: (a) poor communication between neurosurgeon and prosthetist; (b) difficulties in establishing the margins of the defect; (c) orientation of the prosthesis, and (d) marginal retention. All were overcome with an agreed protocol. PMID- 8512908 TI - Late extrusion of alloplastic orbital floor implants. AB - Complications following the use of alloplastic orbital floor implants are well documented but it is not widely recognised that these can occur many years after initial treatment. Three patients who presented with late extrusion of an implant through the facial skin are reported. This complication occurred 10, 16 and 17 years respectively after treatment of the orbital floor fracture. The tissue reaction to silicone rubber and Teflon inplants is reviewed and the possible cause for this late complication is discussed. PMID- 8512907 TI - A preliminary study into the uses of anorganic bone in oral and maxillofacial surgery. AB - Anorganic bovine bone has been used in oral and maxillofacial surgery for several years. Its use has been limited to ridge augmentation. In this paper we have tried to evaluate its use in other settings within the speciality. PMID- 8512909 TI - Ketorolac and diclofenac for postoperative pain relief following oral surgery. AB - A double-blind clinical study was designed to compare the efficacy and safety of intramuscular and oral ketorolac, a new non-steroidal anti-inflammatory analgesic with that of diclofenac and placebo for patients undergoing removal of impacted mandibular third molar teeth. Results showed that both analgesic preparations were more effective than placebo (p = 0.0029) and that ketorolac provided a similar degree of pain relief to that of diclofenac. It is concluded that ketorolac is important new addition to the available intra-muscular NSAID preparations. PMID- 8512910 TI - Tissue response to a haemostatic alginate wound dressing in tooth extraction sockets. AB - Kaltostat is a new haemostatic wound dressing composed of non-woven sodium calcium alginate fibres, and was originally developed to cover exposed wounds of the skin. A histopathological study was undertaken to determine the tissue response to Kaltostat in healing tooth sockets, to obtain a comparison with oxidised regenerated cellulose (Surgicel). Tooth sockets filled with blood clot acted as controls. The results showed that both biomaterials delayed wound healing in the early phase (1-4 weeks), giving rise to foreign body reactions. At 12 weeks there was little difference between the control sockets and the sockets containing the test materials, although remnants of retained dressing materials were identified. Healing of the tooth sockets was complete at 24 weeks. PMID- 8512911 TI - A randomised double blind comparative study of low level laser therapy following surgical extraction of lower third molar teeth. AB - A randomised, double blind comparative study was undertaken to assess the efficacy of low level laser therapy in the reduction of postoperative pain and swelling in patients undergoing the extraction of bilaterally impacted mandibular third molar teeth. Healing of the sockets was also compared after 1 week. A group of 64 patients had one randomly-selected operation side treated with a semi conductor laser and the other side with an apparently identical but non-operating model. Complete data were obtained from 52 of the 64 patients. The results showed that there was no evidence of a difference in pain and swelling on the third day after operation between laser and placebo sides. There was no difference between the two sides when they were assessed for healing 7 days after surgery. PMID- 8512912 TI - Are viruses associated with aphthae and oral vesiculo-erosive disorders? AB - Oral and maxillofacial surgeons in District General Hospitals in UK often carry the major workload of patients with chronic oral ulcerative conditions. Although the immunopathogenic basis of many of these is being unravelled, the aetiology is often unclear, though a role for viruses is increasingly suspected. This paper reviews the current evidence. PMID- 8512913 TI - Fatal disseminated intravascular coagulation complicating dental extraction. AB - A case is reported of fatal disseminated intravascular coagulation occurring 8 h after routine extraction of wisdom teeth in a 24-year-old woman. Since all bacteriological specimens taken were sterile and no other precipitant was found, we believe this case represents an example of the generalised Shwartzman reaction to the local trauma of dental extraction leading to fatal initiation of the coagulation system. PMID- 8512914 TI - Recurrent unicystic ameloblastoma of the maxilla. AB - A previously reported unicystic ameloblastoma, showing luminal plexiform epithelial proliferation and the presence of small islands of odontogenic epithelium in the connective tissue of the cyst wall, recurred 5 years after conservative surgery. The tumour was nucleated and since the epithelial islands were confined to its fibrous capsule a conservative approach was regarded as adequate. In view of the later experience it is now proposed that where cystic ameloblastomas depict epithelial infiltration into the capsule a second excision be considered and that such surgical material be thoroughly examined for signs of epithelial infiltration. Whatever type of treatment the surgeon decides to perform, it is essential to have a long postoperative period of monitoring. Because the presence of islands of odontogenic epithelium in the cyst wall influences the surgical approach, it is recommended that pathologists carefully examine cystic ameloblastoma surgical specimens for their presence. Multiple, even serial sections are required for such examinations. The pathology report should include a description of the islands with an indication of their site in the capsule of the tumour. PMID- 8512915 TI - Intraosseous leiomyoma of the mandible: report of a case. AB - A rare case of intraosseous leiomyoma of the mandible is reported. This is the fourth recorded case involving the mandible. The literature is reviewed and the amenability of the lesion to simple local excision is highlighted. PMID- 8512916 TI - Dysphagia following bimaxillary osteotomy. AB - A case of complete dysphagia, requiring surgical intervention, which occurred following bimaxillary osteotomy is described. A brief resume of the relevant anatomy and physiology is included with a discussion of the possible aetiology of this complication. PMID- 8512917 TI - The use of a metal detector for localisation of a metallic foreign body in the floor of the mouth. AB - The case illustrates the valuable assistance provided by a metal detector in localising an elusive broken instrument which was hidden in a recess on the medial side of the mandibular angle and encapsulated in fibrous tissue. A relative degree of sophistication built into the detector aided early localisation. PMID- 8512918 TI - Modification of a standard aspirator for orbital floor procedures. AB - An inexpensive method of achieving controlled and atraumatic aspiration during orbital floor surgery is described and illustrated. PMID- 8512919 TI - Jehovah's Witness. PMID- 8512920 TI - A diverticulum arising in the lingual sulcus. PMID- 8512921 TI - Prophylaxis for venous thromboembolism. PMID- 8512922 TI - Promoter recognition by Escherichia coli RNA polymerase. Effects of single base pair deletions and insertions in the spacer DNA separating the -10 and -35 regions are dependent on spacer DNA sequence. AB - Escherichia coli RNA polymerase contacts promoter DNA at two upstream regions separated by a spacer DNA. We had previously studied the effects of substitutions of simple DNA sequences in a stretch of the spacer DNA devoid of any known specific contacts with RNA polymerase. It was found that substitution of nine consecutive nonalternating dG-dC base pairs, but not nine alternating dG-dC base pairs, impaired promoter function. We proposed that this effect was due to the fact that the oligo(dG)-oligo(dC) sequence adopted a conformation (possibly A helical) resulting in a reduction in its length and twist as compared with the B form DNA of the alternating sequence. Here we test this hypothesis by combining the substitutions with single base pair insertions and deletions in the spacer DNA, which affect the length and the twist in known ways. Deletion and substitutions equally affect the activities of promoters with the presumed B-DNA substitutions. However, for promoters bearing the oligo(dG)-oligo(dC) substitution, a deletion in the spacer DNA impairs promoter activity to a much greater extent than the insertion of a base pair. This asymmetry is consistent with our hypothesis that the deleterious effects of the substitution are due to its having the reduced twist and/or length characteristic of A-DNA. Additionally, we present data that concern the sequence requirements for adoption of this structure that leads to reduced promoter function. PMID- 8512923 TI - Molecular defect in factor IX Tokyo: substitution of valine-182 by alanine at position P2' in the second cleavage site by factor XIa resulting in impaired activation. AB - Utilizing polymerase chain reaction and directly sequencing the amplified exon 6 of the factor IX gene derived from a mild hemophilia Bm patient, we have identified a T to C mutation at nucleotide 20,525. This point mutation predicted a Val182 to Ala substitution in the abnormal factor IX molecule, designated as factor IX Tokyo. The patient manifested a low factor IX activity and a moderately prolonged ox-brain prothrombin time but a normal factor IX antigen level in plasma. Immunopurified factor IX derived from the patient was found to have a normal molecular weight but a reduced specific activity (23% of normal). Limited proteolysis by activated factor XI or by a snake venom-derived factor X activating enzyme was considerably delayed, indicating the presence of structural alteration(s) most probably at or near the second enzyme-cleavage site. Once activated, however, factor IXa Tokyo was able to activate factor X normally and was inactivated by antithrombin III also in a normal fashion. The structural model of factor IXa and a docking model of factor IX and activated factor VII (factor VIIa) suggested that the Val182 to Ala substitution would not affect the local conformation of the catalytic domain. This mutation would rather loosen the fitness of the molecule into the substrate-binding pocket of factor VIIa due to a shorter side chain of the Ala substitution at the P2' position of the second cleavage site. PMID- 8512924 TI - Investigation of ribonuclease T1 folding intermediates by hydrogen-deuterium amide exchange-two-dimensional NMR spectroscopy. AB - The rate of hydrogen bond formation at individual amino acid residues in ribonuclease T1 (RNase T1) has been investigated by the hydrogen-deuterium exchange-2D NMR (HDEx-2D NMR) technique (Udgaonkar & Baldwin, 1988; Rder et al., 1988) to gain insight into the mechanism and pathways of protein folding. The HDEx-2D NMR technique combines rapid mixing and 2D NMR methods to follow the protection of backbone amide deuterons from exchange with solvent protons as a function of folding time. The technique depends on the difference in the exchange rates of hydrogen-bonded and non-hydrogen-bonded amide residues so that as the protein folds, the amide residues involved in hydrogen bonding are protected from exchange with solvent to give structural information about early folding events. The observed time course for deuterium protection was followed for 24 backbone amide residues that form stable hydrogen bonds in RNase T1. The time courses are biphasic with 60-80% of the protein molecules showing rapid hydrogen bond formation (12-119 s-1) in the alpha-helix and the beta-sheet. The remaining 20 40% of the molecules are protected in a slow phase with a rate constant that has a lower limit of 0.01 s-1. If the rate constants in this first phase are arbitrarily subdivided into two classes, fast (> or = 25 s-1) and intermediate (< 25 s-1), then the amide residues that are found in the hydrophobic core are in the fast class while those located on the periphery of the three-dimensional structure are in the intermediate class.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512925 TI - Crystal structure of selenosubtilisin at 2.0-A resolution. AB - The three-dimensional structure of selenosubtilisin, an artificial selenoenzyme, has been solved at 2.0-A resolution by the method of molecular replacement. Selenosubtilisin is a chemical derivative of the bacterial serine protease subtilisin in which the catalytically essential serine residue has been replaced with a selenocysteine. Its unique hydrolytic and redox properties reflect the intrinsic chemical reactivity of the selenium prosthetic group. Structural analysis of the modified protein reveals that the selenium moiety is selectively incorporated into the side chain of residue 221 and confirms the seleninic acid oxidation state expected from treatment of the enzyme with hydrogen peroxide prior to crystallization. Although the seleninic acid replaces the essential nucleophile in the enzyme's catalytic triad and introduces a negative charge into the active site, the interaction between His64 and Asp32 is not altered by the modification. Hydrogen bonds from the oxygen atoms of the seleninic acid to His64 and to Asn155 in the oxyanion hole confine the prosthetic group to a single well defined conformation within the active site. These interactions thus provide a structural basis for understanding the seleninic acid's unusually low pKa, the enzyme's relatively sluggish rate of reaction with thiols, and its much more efficient peroxidase activity. Aside from the active site region, the structure of the protein is essentially the same as that previously reported for native subtilisin Carlsberg, indicating the viability of chemical modification strategies for incorporating site-specific changes into the protein backbone. Comparison of the three-dimensional structures of selenosubtilisin and glutathione peroxidase, an important naturally occurring selenoenzyme, provides the means to evaluate how the function of the selenium prosthetic group varies with molecular context. PMID- 8512926 TI - Catalytic centers in the thiamin diphosphate dependent enzyme pyruvate decarboxylase at 2.4-A resolution. AB - The crystal structure of brewers' yeast pyruvate decarboxylase, a thiamin diphosphate dependent alpha-keto acid decarboxylase, has been determined to 2.4-A resolution. The homotetrameric assembly contains two dimers, exhibiting strong intermonomer interactions within each dimer but more limited ones between dimers. Each monomeric subunit is partitioned into three structural domains, all folding according to a mixed alpha/beta motif. Two of these domains are associated with cofactor binding, while the other is associated with substrate activation. The catalytic centers containing both thiamin diphosphate and Mg(II) are located deep in the intermonomer interface within each dimer. Amino acids important in cofactor binding and likely to participate in catalysis and substrate activation are identified. PMID- 8512927 TI - The primary self-assembly reaction of bacteriophage lambda cI repressor dimers is to octamer. AB - Cooperative binding of the bacteriophage lambda cI repressor dimer to specific sites of the phage operators OR and OL controls the developmental state of the phage. It has long been believed that cooperativity is mediated by self-assembly of repressor dimers to form tetramers which can then bind simultaneously to adjacent operator sites. As a first step in defining the individual energy contributions to binding cooperativity, sedimentation equilibrium and steady state fluorescence anisotropy methods have been used to study the higher order assembly reactions of the free repressor in solution. Wild-type repressor with 5 hydroxytryptophan (5-OHTrp) substituted for the native tryptophan [Ross et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12023-12027] and two mutant repressor proteins that bind cooperatively to OR but have altered dimerization properties were also studied. We report here that the primary assembly mode of all four proteins is dimer to octamer. It is not dimer to tetramer as previously assumed. While tetramer does form as an assembly intermediate, dimer-octamer assembly is a concerted process so that tetramer is never a predominant species in solution. Sedimentation velocity experiments suggest that the octamer is highly asymmetric, consistent with an elongated shape. This conformation could allow octamers to bind simultaneously to all three operator sites at either OR or OL. Examination of tetramer and octamer concentrations suggests that both species could be involved in cooperative repressor-operator interactions. Our previous work used the unique spectral properties of 5-OHTrp to demonstrate that octamer binds single-operator DNA and is not dissociated to tetramer [Laue et al. (1993) Biochemistry 32, 2469-2472]. Taken together with the results presented here, octamers as well as tetramers must be considered in developing models to explain the cooperativity of lambda cI repressor binding to operator DNA. PMID- 8512928 TI - A single-stranded amphipathic alpha-helix in aqueous solution: design, structural characterization, and its application for determining alpha-helical propensities of amino acids. AB - In order to investigate the positional effect of alpha-helical propensities of amino acids in an amphipathic alpha-helix, an amphipathic alpha-helical model peptide (Ac-Glu-Ala-Glu-Lys-Ala-Ala-Lys-Glu-Ala-Glu-Lys-Ala-Ala-Lys-Glu-Ala-Glu Lys- amide) was designed and characterized by circular dichroism and 2D-NMR spectroscopies. This peptide contains 65% alpha-helical structure in solution, and its monomeric molecular weight in aqueous solution was determined by size exclusion chromatography. The independence of alpha-helical structure and stability on peptide concentration demonstrates that helix formation of this peptide is a monomolecular process. To compare the effect of substitutions in the hydrophobic and hydrophilic face of the helix on structure and stability, a leucine, alanine, or glycine was individually substituted in the hydrophobic face (position 9) or hydrophilic face (position 7) of the model peptide. The change in helix content and stability upon substitution was measured by circular dichroism studies in the absence and presence of TFE or urea. The results indicate that each amino acid has a different helix propensity when it is located in the hydrophobic face versus hydrophilic face and the effect of substitution is more significant in the hydrophobic face. This single-stranded amphipathic alpha helical peptide provides an appropriate model system to determine helix propensities of amino acids on both hydrophobic and hydrophilic faces. PMID- 8512929 TI - Structure of the human C6 gene. AB - The terminal components of the complement system (C6-C9) are related proteins, differing in size and complexity. They seem to be typical mosaic proteins, composed of modules which are homologous with parts of other proteins. Individual elements in a mosaic protein are often bounded by introns in the gene, and where they are duplicated within a polypeptide, partial gene duplication within the gene is responsible. It is often found in such genes that the intron/exon boundaries are of the class 1 type. We have examined the boundaries of 17 of the 18 exons of C6 and five of C7. When considered with published data for C9, only one of the protein elements appears to follow the conventional pattern. These data suggest a more complex evolutionary history for the genes of the terminal complement components than had been anticipated and challenge the notions both that discovery of a recognized protein module is of predictive value in relation to gene structure and that these genes evolved from the simple to the complex. PMID- 8512930 TI - Environmental influences on the in vivo level of intramolecular triplex DNA in Escherichia coli. AB - We describe an assay for detecting intramolecular triple-stranded DNA in living cells. The assay involves quantitative analysis of the differential photobinding of 4,5',8-trimethylpsoralen to 5'TA and 5'AT dinucleotides in a region of plasmid DNA containing the triplex-forming sequence (GA)7TA(GA)7. Psoralen photobinds to the central 5'TA within the (GA)7TA(GA)7 sequence in duplex DNA but not when the sequence exists as an intramolecular triplex structure. The reactivity of photobinding sites in regions flanking the intramolecular triplex-forming sequence, those that comprise the duplex-triplex junctions, either increase or decrease upon formation of the intramolecular triplex structure from duplex DNA. The pattern of trimethylpsoralen reactivity provides an indication of the conformation of the (GA)7TA(GA)7 sequence in plasmid DNA. The formation of the intramolecular triplex structure is dependent on both pH and negative superhelical density in vitro. The fraction of the (GA)7TA(GA)7 sequence that existed as an intramolecular triplex structure in vivo was dependent on the level of DNA supercoiling in vivo and changes in growth conditions which influence the intracellular pH. The Hy3 isomer was detected in living Escherichia coli cells. PMID- 8512931 TI - Copper ion-mediated sensitization of nuclear matrix attachment sites to ionizing radiation. AB - Exposure of mammalian cells to ionizing radiation induces nuclear matrix proteins and their attached transcribing DNA sequences to form cross-links. To characterize the cellular and matrix components necessary for DNA-protein crosslink (DPC) formation, DPC yields have been examined in isolated nuclear matrices and in the intermediate steps during cell fractionation. It was found that, in both unirradiated and irradiated cells, all components of DPC are retained in isolated nuclei, and the formed DPC are retained as well during the cell fractionation procedure resulting in nuclear matrices. In contrast, nuclear matrices isolated from unirradiated cells are deficient in the ability to form DPC upon irradiation, indicating that elements necessary for DPC production have been disrupted or removed during the isolation procedure. When isolated nuclei were irradiated, the yield of radiation-induced DPC was about 2-fold higher than that for intact cells, presumably due to the removal of soluble cellular scavengers during the isolation procedure. Treatment of nuclei with Cu2+ to stabilize nuclear structural organization during the preparation of the nuclear matrix caused additional DNA, especially the matrix-associated newly replicated DNA, to become bound to protein. Such treatment also enhanced radiation-induced DPC production which was sensitive to OH radical scavengers. Moreover, radiation induced DPC production in Cu(2+)-treated nuclei was more sensitive to EDTA and catalase than in untreated nuclei. It is therefore proposed that excess DPC induction in Cu(2+)-treated nuclei occurs preferentially at the sites of Cu2+ binding to chromatin where hydroxyl radicals are produced repeatedly through the Fenton reaction. PMID- 8512932 TI - Parallel and antiparallel G-DNA structures from a complex telomeric sequence. AB - We investigated the formation in vitro of higher order structures by a DNA oligomer containing the terminal motif TGTG3TGTGTGTG3, derived from the Saccharomyces telomeric consensus, in order to (a) understand why certain cations favor the formation of parallel-stranded (G4 and G8) G-DNA structures, while others favor foldback, antiparallel structures (G'2) and (b) probe the structures of G-DNAs formed by this telomeric sequence, which is more complex than its well studied counterparts from the protozoans oxytricha and tetrahymena. We find that dramatic switches in the formation of G4 versus G'2 structures occur in solutions of not only the group Ia cations, Li(+)-Cs+, but also in those of the group IIa cations, Mg(2+)-Ba2+. These data and the temperature-dependent formation and destruction of the different structures lend support to the kinetic scheme of Sen and Gilbert (1990), by which rapidly forming G'2 structures accumulate in highly stabilizing potassium (and strontium) solutions at the expense of the thermodynamically more stable G4 structures. Both the G4 and the G'2 complexes formed by the Saccharomyces sequence show novel structural features. Protection and interference experiments with dimethyl sulfate and potassium permanganate reveal that the core of alternating thymines and guanines within the telomeric motif plays a critical role in the stabilization of the parallel G4 structure, but not of the antiparallel G'2. Very likely, in the G4 complex, this GT core forms a novel higher order arrangement of alternating G and T quartets, the latter possibly comparable to the U quartets described by Cheong and Moore (1992) in their NMR study of the higher order structure formed by rUG4U. PMID- 8512933 TI - Hormone- and DNA-binding mechanisms of the recombinant human estrogen receptor. AB - We have investigated the hormone- and DNA-binding mechanisms of the wild-type human estrogen receptor (hER) overproduced in insect cells using a baculovirus expression system. The recombinant hER was indistinguishable in size (67 kDa) and immunogenically from the native human estrogen receptor in MCF-7 breast carcinoma cells. The recombinant hER was purified to 70-80% homogeneity with a two-step procedure that included ammonium sulfate precipitation and oligonucleotide affinity chromatography using a unique Teflon affinity matrix. The recombinant hER bound estradiol with a positively cooperative mechanism. At hER concentrations in excess of 13 nM the Hill coefficient reached a maximal value of 1.6, whereas, at lower hER concentrations, the Hill coefficient approached 1.0, suggesting that the hER was dissociated to the monomeric species and site-site interactions were diminished. The hER specifically bound an estrogen responsive element (ERE) from chicken vitellogenin II gene as measured by the gel mobility assay, ethylation, and thymine interference footprinting. Specific interference patterns suggest a two-fold symmetry of the hER binding to the ERE with each monomer of the hER bound in the major groove of the DNA. These data indicate that the recombinant hER is valuable to define the biochemical and structural properties of the native estrogen receptor. PMID- 8512934 TI - Quinacrine and ethidium bind to different loci on the Torpedo acetylcholine receptor. AB - Fluorescence spectroscopy was used to determine whether quinacrine and ethidium, two high-affinity noncompetitive inhibitors of the Torpedo acetylcholine receptor (AcChR), bind to the same loci. The ability of three nitroxide spin-labels, 5 doxylstearate (5-SAL), spin-labeled androstane (ASL), and TEMPO, to quench receptor-bound quinacrine and ethidium fluorescence was measured. When bound to a phencyclidine-displaceable site on the AcChR, quinacrine was 16.9 and 19 times more efficiently quenched than ethidium by the highly lipophilic 5-SAL and ASL, respectively. TEMPO, which has a limited ability to partition into Torpedo plasma membranes (< 1%), was only twice as efficient at quenching receptor-bound quinacrine than ethidium fluorescence. The relative sensitivity of quinacrine and ethidium fluorescence to paramagnetic quenching was examined in three solvents, 1 butanol, sodium phosphate buffer, and acetonitrile, with TEMPO as a quencher. The results from the different solvents demonstrate that quinacrine fluorescence is intrinsically 1.4-3.6 times more sensitive than ethidium fluorescence to quenching by nitroxide spin-labels. Examination of the effect of high concentrations of 5-SAL on ethidium and quinacrine dissociation constants showed that quinacrine but not ethidium binding was competitively inhibited. Together, these results indicate that although quinacrine and ethidium bind in a mutually exclusive manner, the two inhibitors interact at different loci on the AcChR. Whereas the ethidium binding site is at a distance from membrane lipids, probably in or near the lumen, the quinacrine binding site appears to be at a lipid protein interface in the transmembrane domain and at a distance from the lumen. PMID- 8512935 TI - Random mutagenesis of the substrate-binding site of a serine protease can generate enzymes with increased activities and altered primary specificities. AB - In the past, several point mutations have been introduced individually into the substrate-binding site of alpha-lytic protease (EC 3.4.21.12) and shown to affect its specificity in a predictable manner [Bone, R., Silen, J. L., & Agard, D. A. (1989) Nature 339, 191-195]. One of the resulting mutant enzymes (Met190Ala in the numbering system of Fujinaga et al.) [Fujinaga, M., Delbaere, L. T. J., Brayer, G. D., & James, M. N. G. (1985) J. Mol. Biol. 183, 479-502] cleaves at large hydrophobic residues. We chose this enzyme as the parent for a library of mutant proteases. The library was constructed by effecting combinatorial random substitution of up to four other residues (Gly191, Arg192, Met213, and Val218) thought likely to influence the primary specificity of the protease. Active enzymes in the library were screened with a range of synthetic substrates (encompassing 19 different amino acids in the P1 position) in order to evaluate their primary cleavage preferences. The amino acid sequences of active mutants revealed a strong preference for the replacement of Met213 with a His residue. This substitution also had the greatest observed effect on specificity, conferring a greatly increased and, in some cases, dominant ability to cleave at His residues in synthetic amide substrates. Mutant enzymes with greatly increased proteolytic activity were also found in the library. PMID- 8512936 TI - Substrate recognition at the binding site in mammalian pancreatic alpha-amylases. AB - Porcine and human pancreatic alpha-amylases (PPA and HPA, respectively) have five binding sites for hexose residues of substrates. As previously reported, when a substrate is too small to occupy subsite 5 of the alpha-amylases, the optimum pH for catalytic activity changes from neutral to acidic [Ishikawa, K., Matsui, I., Honda, K., & Nakatani, H. (1990) Biochemistry 29, 7119-7123]. We studied the mechanism by which the enzyme recognizes the substrate by using the synthetic substrates maltopentaose (G5) and its analogs 4-O-alpha-maltotetraosyl-D-xylose (G4-X), 4-O-alpha-maltotetraosyl-2-deoxy-D-glucose (G4-D), 3-O-alpha maltotetraosyl-L- sorbose (G4-S), 4-O-beta-maltotetraosyl-D-glucose (G4 beta-G), alpha-maltotetraosyl-beta-D-fructose (G4-F), p-nitrophenyl alpha-maltotetraoside (G4-phi), and maltopentaitol (G4-GOH). The reducing-end residues of these substrates, relevant to subsite 5, are D-xylose (X), 2-deoxy-D-glucose (D), L sorbose (S), D-glucose (G), alpha-D-fructofuranose (F), p-nitrophenyl (phi), and D-sorbitol (GOH), respectively. The optimum pH for catalytic activity on the substrates G5, G4-X, G4-D, G4-S, G4 beta-G, and G4-phi was neutral, while that for G4-GOH and G4-F was acidic. These results indicate that only six-membered ring residues and a phenyl group are recognizable by subsite 5. The neutral pH profile for G4-phi suggests that steric compatibility of the substrates at subsite 5 is also important for the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512937 TI - Mathematical analysis of a proteolytic positive-feedback loop: dependence of lag time and enzyme yields on the initial conditions and kinetic parameters. AB - A model of a proteolytic positive-feedback loop, similar in general terms to feedback loops that occur in blood coagulation and other systems, has been examined by both explicit and numerical analysis. In this loop, modeled as a closed system, each enzyme (E1, E2) catalyzes the formation of the other from its respective zymogen (Z1, Z2), and both enzymes are subject to irreversible inhibition. The system shows three major characteristics. (1) No significant Z1 or Z2 activation occurs unless the combination of initial conditions and kinetic parameters is above a threshold level. This threshold occurs when the product of the enzyme generation rates equals the product of their inhibition rates. When the formation-rate product is less than the inhibition-rate product, there is no response: E1 and E2 generation is minimal and the lag time is effectively infinite. Conversely, when the generation-rate product exceeds the inhibition rate product, explosive formation of both E1 and E2 is seen. For responses exceeding the threshold, the following obtain. (2) The lag time in E1 and E2 generation is a highly nonlinear function of the zymogen concentrations and the enzyme generation and inhibition rates. In contrast, there is a simple logarithmic relationship between the lag time and the initial trace concentration of the enzyme that is responsible for initiating the system; in this model, E1. (3) The extent of Z1 and Z2 activation is similarly a nonlinear function of the conditions and parameters but is independent of the initiating trace level of E1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512938 TI - An exact general analysis of ligand binding displacement and saturation curves. AB - Quantitative analysis of a ligand-protein interaction relates binding to the free concentration of ligand molecules in solution. A theoretical analysis is presented herein, by which intermolecular interactions can be described as a function of the added concentrations of ligand molecules. Following this analysis, ligand binding displacement and saturation curves can be converted directly into a linear form, even when nonradioactively labeled ligands are used to detect the ligand-protein interaction. From the linearities obtained, relevant binding parameters, including the binding dissociation constant, can be calculated. On the basis of this analysis, binding parameters have been characterized for the interaction between biotin-protein A and immunoglobulins, using ELISA-type detection, and for the interaction of a fluorescently labeled fatty acid with a specific fatty acid binding protein. PMID- 8512939 TI - Quantitative IR studies of acyl chain conformational order in fatty acid homogeneous membranes of live cells of Acholeplasma laidlawii B. AB - Acholeplasma laidlawii B has been grown highly enriched in myristic, pentadecanoic, and palmitic acids. The conformational order in the acyl chains of living cell membranes has been compared with that in the membranes of lysed cells and the lipids extracted therefrom, using Fourier-transform infrared (FT-IR) spectroscopic techniques. A gel-liquid-crystal-phase transition (25-45 degrees C) was noted for both the live cells and the membranes. Surprisingly, CH2 wagging progressions, characteristic of coupled oscillators from acyl chains in the all trans conformation, were detected in the live cells and in the cell membrane. A simple model suggested the presence of 1.7 gauche bonds/chain at the growth temperature (37 degrees C) in each case. Conformational order in the live cells and in the membranes was virtually identical over the range of cell viability (5 40 degrees C), as measured by the thermotropic responses of the k = 1 and k = 2 components of the wagging mode progression. This result was confirmed by studies of the thermotropic response of the symmetric CH2 stretching vibrations, a qualitative index of acyl chain order. In contrast, the membrane lipid extracts (i) show much more conformational disorder from 5 to 25 degrees C than either the live cells or the membranes, (ii) undergo a gel-liquid transition over a broader temperature range and with a reduced magnitude of change in the symmetric CH2 stretching frequency, and (iii) demonstrate a second transition centered at 50 degrees C, which is detected by a large increase in the localized CH2 wagging mode (1368 cm-1) that arises from conformationally disordered kink+gtg states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512940 TI - Infrared spectroscopic study of a "hard-to-exchange" phospholipid population in the vicinity of CaATPase. AB - CaATPase from rabbit sarcoplasmic reticulum (SR) has been isolated, purified, and reconstituted into unilamellar vesicles with 1,2 dipentadecanoylphosphatidylcholine (DPePC) and acyl-chain-perdeuterated 1,2 dipalmitoylphosphatidylcholine (DPPC-d62). For total lipid:protein mole ratios between 25 and 70, a constant "hard-to-exchange" phospholipid population (HEPP) of 12 +/- 4 native phospholipid molecules per protein monomer is observed, consistent with the studies of Bick et al. [(1991) Arch. Biochem. Biophs. 286, 346-352]. Thermotropic and conformational properties of the lipids in native SR and in the reconstituted systems were probed with FT-IR spectroscopy. The native SR phospholipids undergo a broad phase transition centered at about 1-2 degrees C and are thus disordered under physiological conditions. The thermotropic behavior of CH2 wagging progressions characteristic of the palmitate chains differs from that of the total lipid population and is suggestive of membrane microheterogeneity. The individual thermotropic and conformational properties of the HEPP and the exogenous lipid in reconstituted vesicles containing CaATPase and DPPC-d62 were monitored. At temperatures below the onset of the gel-liquid crystal phase transition, the HEPP possesses significant conformational disorder, and exhibits the monotonic introduction of gauche rotamers as the temperature is raised from -55 to 27 degrees C, in contrast to the exogenous lipid, which exhibits a constant high order over the same temperature range. Nevertheless, the HEPP undergoes a residual order-disorder phase transition with similar but not identical parameters (half-width, midpoint temperature) to the gel-liquid-crystal transition of the bulk (exogenous) lipid in the reconstituted systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512941 TI - Physical heterogeneity of muscle glycogen phosphorylase revealed by hydrostatic pressure dissociation. AB - Four independent methods that employ fluorescence spectroscopy show that the tetramer of glycogen phosphorylase A (GPA) from rabbit muscle is reversibly dissociated into monomers by hydrostatic pressures under 2.5 kbar, if aggregation of the monomers is prevented by the addition of 8% glycerol. The free energy of association at 20 degrees C (-32 kcal mol-1) depends upon a large entropy increase (T delta S = +65 kcal mol-1) that counteracts an unfavorable enthalpy of association of +33 kcal mol-1. The association volumes calculated from the pressure dependence of the dissociation are nearly 4-fold smaller than those calculated from the shift in dissociation pressure with concentration. The dimer obtained by dilution of GPA at atmospheric pressure differs from the hypothesized dimer intermediate in the pressure dissociation by the much larger monomer affinity of the former. Like other tetramers, GPA shows hysteresis of the pressure profile upon decompression and conformational drift of the dissociated monomers. By use of the energy transfer method it is demonstrated that the relaxation time for half-dissociation (5 min) is over an order of magnitude shorter than that for subunit exchange (118 min). In all three tetramers studied, lactate dehydrogenase, glyceraldehyde phosphate dehydrogenase, and glycogen phosphorylase, the deterministic character of the dissociation equilibrium under pressure and the anomalous concentration dependence of the pressure dissociation demonstrate that these tetramers are heterogeneous populations with regard to their free energy and/or volumes of association. PMID- 8512942 TI - Non-isotopic detection of single-stranded conformation polymorphisms using ethidium bromide/UV light. AB - In the course of searching for single base substitutions resulting in polymorphisms or point mutations within the adenomatous Polyposis coli (APC) gene we established an alternative non-radioactive procedure to detect single-stranded conformation polymorphisms (SSCP) of polymerase chain reaction (PCR) products. A fast and inexpensive SSCP assay system is described in detail with general application allowing the non-isotopic identification of single base alterations of PCR products. This was achieved by combining heat denaturation of PCR products resulting in a high yield of single-stranded DNA and ethidium bromide staining of separated DNA strands in non-denaturing polyacrylamide vertical standard gels. The validity of the non-radioactive procedure described here is demonstrated by the identification of allele-specific SSCP patterns derived from intragenic polymorphisms of the APC gene. PMID- 8512943 TI - Exploratory data analysis in two-dimensional electrophoresis. AB - The use of computerized matching of proteins in the analysis of multiple two dimensional electrophoresis (2DE) gels creates volumes of data that are readily accessible for exploratory analysis. When these data are used in health-effects studies or in studies to identify factors associated with particular diseases, hundreds or even thousands of hypotheses can be tested. Interpreting so many hypothesis tests requires some preliminary statistical evaluations of the data. In addition, prior to the preliminary statistical evaluations and subsequent hypothesis tests, accurate protein quantification and correct protein matching must be verified. In this report we present an approach used at the Centers for Disease Control to address these issues. This approach consists of a randomized experimental design incorporating replicate gels for each specimen, gel image analysis, protein matching, editing, Boolean unions of all gels to obtain correspondences and contradictions of match identification numbers, resolution of correspondences and contradictions, statistical tests to identify outliers, and finally an assessment of statistical and practical significance to focus attention on the proteins most likely to be associated with the effects under study. We illustrate our approach with data from an exploratory exposure-response study. PMID- 8512944 TI - Quantitative two-dimensional electrophoretic detection of possible urinary protein biomarkers of occupational exposure to cadmium. AB - To search for new urinary protein biomarkers of cadmium toxicity, we used quantitative two-dimensional electrophoresis (2DE) and analysed urine samples from 18 male cadmium recovery plant employees whose mean age was 47 +/- 15.6 years (+/- 1 SD) and whose urine cadmium levels ranged from 0.14 microgram l-1 to 20.4 micrograms l-1 (0.06-37.1 micrograms g-1 creatinine). Image analysis of the silver-stained gels yielded intensity (concentration) values for a mean number, per person, of 825 +/- 184 urinary proteins (spots) and found 596 +/- 218 matched proteins (the same proteins in two or more gels) per person. Total urinary protein and the sum of all spot intensities were positively correlated (P = 0.0447 and P = 0.0616, respectively) with urinary cadmium (UCD), as measured by atomic absorption spectroscopy. The combined sum of the intensities of all acidic proteins with a relative molecular weight (M(r)) below 40 kDa was correlated with UCD (P = 0.0461), revealing a low M(r), acidic proteinuria as UCD increased. Multiple hypothesis testing by regression analysis of the intensities of matched proteins with UCD revealed 14 unidentified proteins that were considered candidates for biomarkers of cadmium exposure. The best two candidate proteins- those having M(r)s of less than 13.9 kDa and relative glyceraldehyde-3-phosphate dehydrogenase (G3PDHr) coordinates of -19.7 and -27.2--were excellently resolved in the 2DE gels, and their intensities increased by 323% and 857%, respectively, over the UCD range that was tested. Two other proteins with M(r)s of 23.9 kDa and 29.2 kDa and with acidic net charges were not as well resolved. Six very acidic proteins, with M(r)s ranging from 88.8 to 90.7 kDa and with intensities highly correlated with UCD, appeared to be related and were resolved as a 'charge train' (a group of related proteins, or isoforms, differing only by small changes in net charge). Four proteins appeared to increase only when the UCD concentration was above a threshold of 16 micrograms l-1. PMID- 8512946 TI - Use of resonance ionization spectroscopy to detect DNA bands on ultrathin spin coated gels. AB - Development of alternative electrophoresis procedures are necessary for large volume sequencing and mapping studies. The use of stable isotopes as DNA labels and ultrathin gels promises to greatly increase the rate of sequencing. Spin coating is presented as an alternative method for producing ultrathin polyacrylamide gels. The technique has the potential of producing gels of micron to submicron thicknesses by varying the viscosity of the acrylamide solution and the spinning speed. Thirty micron thick 6% (weight %) gels were produced in this manner. Tin-labeled DNA oligomers were electrophoresed and detected using sputter initiated resonance ionization spectroscopy (SIRIS). The usefulness of SIRIS and laser atomization RIS (LARIS) to sample the surface and deeper layers of 240 microns thick gels was investigated. With LARIS, whole cross-sections of the gel can be atomized, possibly allowing complete sampling of labels. PMID- 8512945 TI - Exact behaviour of single-stranded DNA electrophoretic mobilities in polyacrylamide gels. AB - We demonstrate the existence of a gel edge effect where the velocity of the samples varies in the first and last centimetres of the gel. In spite of this effect, a differential method of velocity determination leads to exact mobility data. Further analysis against DNA length N and electric field E shows that the molecules always migrate according to an A/N+B(E) law, except in a limited range of E and N, whereas a 1/N1.6 entropic driven regime is found. Below a threshold electric field intensity B(E) varies as E2, in good agreement with the biased reptation mechanism, while at stronger electric fields intensities, B(E) stays constant. This second mechanism is not described by any actual theory, but might be attributed to a geometration-like mechanism. Implications of our findings in sequencing electrophoresis are discussed. PMID- 8512947 TI - Splitting merged spots in two-dimensional polyacrylamide gel electrophoresis gel images. AB - We describe a heuristic computer algorithm using boundary analysis for improving spot finding and spot quantitation of large saturated or near-saturated spots in two-dimensional polyacrylamide electrophoresis gels. This spot quantitation is done using spot segmentation, which consists of spot finding and subsequent quantification steps. Occasionally, clusters of large saturated spots may become merged during spot finding. To correct this, the merged spots must be cut apart before quantitation. It is generally obvious from viewing the merged spot's border where they should be cut--at opposing saddlepoints (concavities in the boundary). The algorithm uses an analysis of the missegmented spot's boundary when a saturated spot is detected. If a near-saturated spot is larger than a given size, the spot segmenter program attempts to merge saturated fragments. When merging occurs, the segmenter program analyses the boundary to see if the spot should be split. The new algorithm first finds all robust concavities and then tries to match complementary ones. These paired concavities are then used to guide cutting of the missegmented spot into two or more separate spot regions. Finally, control is returned to the segmenter program to reprocess the data as a set of smaller separated spots. PMID- 8512948 TI - Resolution of DNA in the presence of mobility modifying polar and nonpolar compounds by discontinuous electrophoresis on rehydratable polyacrylamide gels. AB - Ultrathin-layer rehydratable gels were surface loaded and run in the horizontal position to study effects of mobility modification of DNA. Mobility modification of DNA fragments was achieved by the addition of nonpolar monosaccharides and their corresponding sugar alcohols as well as with glycerol and ethylene glycol in the leading ion buffer. These compounds show little effect when included in the trailing ion buffer. Disaccharides show no mobility modification. Trailing ions such as serine and members of the Good buffer series reduced also the RF of double- or single-stranded DNA. While beta-alanine had no effect, serine and members of the Good buffer series, particularly MOPSO, showed a marked ability to decrease the RF; presumably due to changing the unstacking limits. Rapid separation of sequencing gels with high resolution was achieved with discontinuous buffer systems. The potential methodology for high-resolution scanning of gels as DNA zones unstack from the moving boundary is suggested. PMID- 8512949 TI - Plasma/serum protein patterns in human fetuses and infants: a study by high resolution two-dimensional polyacrylamide gel electrophoresis. AB - Plasma/serum proteins of fetal blood samples (N = 88) obtained under ultrasound guidance between the 18th and the 39th week of pregnancy, of blood samples collected from premature infants (N = 19), newborns at term (N = 20) and children of less than 5 years of age (N = 55) were analysed by high-resolution two dimensional polyacrylamide gel electrophoresis. By comparison with adult 'reference' protein maps, tens of different proteins (and some of their genetic variants) were identified on the electrophoretograms. After the 18th week of gestation, albumin, transferrin, Factor B, glu- and lys-plasminogen, antithrombin III, Gc-globulin, alpha 1-antitrypsin, alpha 2-HS-glycoprotein, several apolipoproteins (apo A-I, A-II, A-IV, C-II, C-III, D, E, J), retinol-binding protein, transthyretin and alpha-fetoprotein could be observed. During intrauterine life, the size of the spots corresponding to alpha-fetoprotein progressively decreased, whereas the protein pattern globally showed an increase in the number and in the size of the spots. These modifications were particularly apparent in the regions of the electrophoretograms restricted to the heavy and light chains of IgG and to alpha 1-antichymotrypsin. In addition, we observed an unidentified fetal polypeptide characterized by an apparent molecular weight (M(r)) of 46 kDa (P46) and a pI of 5.0. P46 was present in all fetuses and all infants of less than 2 years of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8512950 TI - [Study of free radical reactions in proteins by a recombination-kinetic method]. AB - In terms of the polychronous kinetics model there were obtained values of efficient activation energy (Eeff) for a slow reaction of the death of free macroradicals in UV-irradiated at 77K silk fibroin and tendons with 80 and 15% humidity. In silk fibroin Eeff equals 6 +/- 1 kkal.mole-1 at 313-413 K and 14 +/- 1 kkal.mole-1 at 413-453 K. In the tendons with 80% humidity at 193-233 K Eeff = 1 +/- 0.5 kkal.mole-1, and at 233-252 K Eeff = 2 +/- 0.5 kkal.mole-1. In the tendons with 15% humidity in the region of 313-373 K there is a distribution for Eeff from Emin = 0 kkal.mole-1 to Emax = 33 +/- 1 kkal.mole-1. At 373-413 K Eeff = 0. PMID- 8512951 TI - [Assessment of the conformational stability of various classes of human lens crystallins using a monomolecular layer method]. AB - Surface denaturation kinetics of different classes of crystallins have been studied by monolayer technique at air-NaCl solution interfaces. An increase of the conformation stability puts in the following order: pre-alpha << alpha approximately equal to beta H approximately equal to beta L approximately equal to gamma. PMID- 8512952 TI - [Luminescence of nucleohistone, excited in the 120-350 nm region of the spectra]. AB - It is shown that luminescence spectra of DNA, total histone (TH) and nucleohistone (NH) are the same under UV and VUV excitation. The luminescence quantum efficiency falls with a decrease of excitation wave length to 120 nm. This effect is connected with absorption screening of aliphatic amino acids, peptide, and ribosophosphate groups (lambda < 220 nm), with photoionization of DNA (160-120 nm) and photodestruction of tyrosine in TH (lambda < 200 nm). PMID- 8512953 TI - [Oscillations of intracellular pH values and the character of its distribution in immunocompetent cell populations]. AB - Experimental measurements of intracellular pH kinetics detect intracellular pH (pHin) rhythms with a period about an hour and an amplitude comparable with the standard deviation of pHin in cell population. It was shown that pHin oscillations were probably to affect the experimental pH-distribution pattern. The pH-distribution of the population at normal physiological state is usually close to the normal pattern. The time-course of the pHin value for the cell population was shown to have a pattern of a kind of beatings to get the normal pH distribution. Distributions of several "beating"--functions were used to approximate an experimental pH-distribution of immunocompetent cell population. PMID- 8512954 TI - [Effectiveness of synaptic excitation of nerve cells depending on duration]. AB - With a model of a dendritic fibre it was established that with fixed expenditure of mediator the optimal duration of synaptic discharge exists and provides for the soma maximum potential. The estimate of the optimal discharge duration for real nerve cell is near to the experimental measurement. PMID- 8512955 TI - [A mathematical model of neuronal plasticity]. AB - A model of the neuron is proposed which is capable of learning with a teacher. The model is based on hypothetic chemical processes which can proceed in a real nerve cell. It is shown that such model having O(N2) elements of the memory is capable of dividing in two classes O(N2) of different input images, where N is the dimensionality of the input vector. PMID- 8512956 TI - [The effect of blood cell status on cytochemical reactions]. AB - Using luminescence microspectroscopy, it was shown that the cytochemical reaction between acridine orange and nucleic acids of fixed blood cells in smears depends on the physical state of these cells during the study. On fixation, the cellular membrane transforms into a semipermeable envelope thus causing an increase in size and light scattering of cells under the action of osmotic pressure of solvents used to wash the preparations. As a consequence, the migration of energy from monomers to dimers increases, which should be taken into account when interpreting the data on the cytochemical reaction. PMID- 8512957 TI - [Redox transformations of spin probes during interaction with isolated myocardium in ischemic and reperfusion conditions]. AB - It has been shown, that a certain part of spin labels TEMPO, TEMPAMINE or TEMPOL undergoes redox-transformations during the perfusion of rat isolated working hearts. The kinetic parameters of the redox-transformations depend on the duration of the ischemia period. PMID- 8512958 TI - [The mechanism of force generation in muscles]. AB - The mechanism of sliding force generation under contraction in striated muscle is proposed. The basis of the supposed mechanism is electromechanical effect in cross-bridges and actin filaments, which consists in exciting bending and torsional mechanical vibrations in those structures when the electrical charges flow through them. A quantitative estimation of the generated force is given. The models of the muscle contraction founded on the proposed mechanism are considered and discussed. PMID- 8512959 TI - [Effect of low intensity laser radiation with various wavelength on bone marrow immunopoiesis progenitors]. AB - Effects of helium-neon and cadmium-neon lasers with wavelength 632.8 and 470 nm correspondingly with power 20 mw and also argon laser with wavelength 480 nm, power 1 w on "early" and "late" colony-forming units (CFU) of mice bone marrow were appreciated. The helium-neon laser as compared to the cadmium-neon one stimulated the "late" CFU and incorporation of 3H-thymidine in DNA of the bone marrow cells after 30 or 45 min exposition. The more powerful argon laser after 30 min exposition suppressed "early" and "late" CFU completely by 50% dead cells of the bone marrow. A decrease of the argon laser exposition to 5 min was accompanied, by the preservation of the bone marrow cells viability at the control level and ability to stimulate "early" CFU. PMID- 8512960 TI - [A possible mechanism for treating retinal dystrophy with an electromagnetic field]. AB - A mathematical model is proposed that explains restoration of vision by electro magnetic treatment of the retina dystrophy induced only by pathology of receptive cells. Possible relationship between the treatment efficiency and dystrophy localization is shown. PMID- 8512961 TI - [A weak low-frequency magnetic field initiates the frequency dependent fluctuations of Daphnia magna heart contraction period]. AB - The influence of low-frequency (16 Hz) sinusoidal magnetic field on period of Daphnia magna heart beatings was studied. Heart beatings were registered by optical method. Fluctuations of period of heart beatings were analyzed using fast Fourier transform algorithm. It was shown that alternating (16 Hz) magnetic field with magnetic induction of 140 microT combined with direct magnetic field (magnetic induction of 21 microT) causes the appearance of frequency-dependent maxima in the power spectra of heart beating fluctuations. The dynamics of the field effect was studied as the phases of its development, rise and fall, as well as temporal characteristics were determined. It was proposed that sensor of low frequency magnetic field is incorporated in one of the regulatory pathways, controlling rhythmical beating activity. PMID- 8512962 TI - [Effect of SHF-radiation on spontaneous impulse activity of cerebral cortex slices in vitro]. AB - The effect of microwaves field (900 MHz), pulse modulated at frequencies of 7, 16 and 30 Hz, on spontaneous electrical activity (SEA) of cerebral cortex slices of guinea-pig has been studied. Microwaves were shown to induce an irreversible decrease in repetitive rate of SEA. Conventional heating with the temperature rise above that during irradiation produced the same but reversible effect. It is suggested that the microwave effect on SEA is complex consisting of thermal and athermal components. PMID- 8512963 TI - [The state of a protein in microstratified aqueous-organic solvents]. PMID- 8512964 TI - [Stable accuracy of motion automatism as a biochemical indicator of motor homeostasis]. PMID- 8512965 TI - [Isoenergetic model of strength action of antagonistic muscles]. PMID- 8512966 TI - [Selective digestive decontamination: reflections on the European Consensus Conference]. PMID- 8512967 TI - [Microbiological diagnosis of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Review of 5 years at the Hospital de Galdakao]. AB - BACKGROUND: With the aim of knowing the etiology of infectious peritonitis in patients undergoing continuous ambulatory peritoneal dialysis in our Hospital and the yield of our method of culture, we have made a revision of cases recorded during a five years period. METHODS: The peritoneal fluids of 105 patients with peritonitis was processed as following: 10 ml of uncentrifuged liquid was placed in hemocultures bottles, aerobe and anaerobe (Hemoline, Biomerieux) and incubated for up to 15 days at 37 degrees C. An additional 50 ml of peritoneal fluid was centrifuged and the sediment used for Gram stain and placed on enriched chocolate agar. Plates were incubated for up to two days at 37 degrees C in 5% of CO2. During the last year of the review the sediment of 50 ml resuspended in sterile distilled water was placed, too, in hemoculture bottles. In 18 cases we had only the hemoculture bottles inoculated by the nurse of the Nephrology Service (those patients came at a time when the laboratory was closed). Subcultures were identified with routine methodology. RESULTS: 96 (91.43%) of the 105 dialysis effluents processed were culture positive; 91.67% were bacterial and 8.33% fungal peritonitis. 64 (69.56%) of the bacterial isolates were Gram positive and 28 (30.43%) Gram negative. CONCLUSION: We remark the good yield of a simple culture method and the high rate of Gram negative and fungal peritonitis. PMID- 8512968 TI - [Comparison of ATB STREP, AMS-Vitek GPS-TA, and disk diffusion for the detection of a high level of aminoglycoside resistance in Enterococcus spp]. AB - BACKGROUND: The absence of the synergic effect between beta-lactam and aminoglucoside versus Enterococcus is predicted by the presence of a high level of resistance to aminoglucoside. There are several commercial systems which include wells for the performance of this determination for streptomycin and gentamicin. METHODS: A comparative study of two commercial systems, Vitek GPS-TA and ATB STREP (Biomerieux) and disk diffusion versus the Mueller-Hinton agar dilution method used as a method of reference. Two hundred ninety strains of Enterococcus spp. from blood, wounds, pus, fluids from paracentesis and urine were studied. RESULTS: By the reference method, 17 presented high level of resistance only to gentamicin, 45 only to streptomycin, 46 to both and 182 were sensitive to the two antibiotics. The sensitivity of ATB STREP, Vitek GPS-TA and disk diffusion was respectively for high level of resistance to gentamicin of 96.8, 100 and 100% and specificity of 99.5, 99.1 and 96.5%. For high level of resistance to streptomycin sensitivity was 78.2, 100 and 100% and specificity 96, 79.4 and 72.4% respectively. CONCLUSIONS: The authors consider the three methods valid for the determination of high level of resistance to gentamicin, presenting excellent correlation between the results of the reference methods. However, for high level of resistance to streptomycin with ATB STREP 1/5 of the resistant strains would not be detected due to low sensitivity. With Vitek GPS-TA and disk diffusion, although excellent sensitivity was presented, a high percentage of false positives were obtained due to low specificity, thus the authors recommend that before a results of resistance be decided the same should be confirmed by another alternative method (agar dilution, macrodilution in tubes or death-time curve). PMID- 8512969 TI - [Production of hepatitis B virus from peripheral blood lymphocytes stimulated with phytohemagglutinin]. AB - BACKGROUND: It was studied the production of HBV from lymphocytes from peripheral blood induced with a mitogen agent as phytohemagglutinin (PHA), in patients infected by HIV. METHODS: The methodology developed included the culture of peripheral blood mononuclear cells and its induction to proliferate with PHA, in order to study the viral activity in the supernatants of the cultures by detection of HIV-Ag (ELISA), HBsAg (ELISA) and DNA-HBV (Dot-blot). RESULTS: Production of HBV in 23 out of the 42 patients included in this study, corresponding to 21 anti-HIV positive and 2 anti-HIV negative. CONCLUSIONS: Induction to proliferate lymphocytes with a mitogen agent as PHA may represent an alternative way of culture to study interactions between HIV and HBV. PMID- 8512970 TI - [Subcutaneous venous reservoirs: comparative study of their efficacy in patients with AIDS versus oncology and hematology patients]. AB - BACKGROUND: Chronic venous access may constitute a serious problem in some patients and the subcutaneous venous reservoirs have demonstrated to be a useful alternative. AIDS patients require intense pharmacologic treatment, thus the use of subcutaneous venous reservoirs may be specially useful. However, the prevalence of septic type complications following placement of the subcutaneous venous reservoirs in these patients is particularly high. AIMS: To know the efficacy of subcutaneous venous reservoirs in the AIDS population and compare the results in a non AIDS population. METHODS: All the subcutaneous venous reservoirs placed between January 1990 and December 1992 were prospectively studied with two groups being established: Group I: patients with positive serology for HIV and who achieved criteria of AIDS requiring placement of a subcutaneous venous reservoirs. Group II: All the remaining patients in whom a subcutaneous venous reservoirs was placed during the same period of time. RESULTS: The incidence of infection was higher in group I (AIDS) with respect to group II (0.1 versus 0.014 infections/100 catheters/day, p < 0.01) and the non septic complications were higher in group II (3.6% versus 12.7%, p < 0.0004). The catheters were most frequently used in group I with respect to group II (12.7 +/- 7.1 versus 3.3 +/- 4.9 punctures/month) but the period was use longer in group II (13.7 +/- 9.2 versus 4.3 +/- 3.1 months, p < 0.0001). CONCLUSIONS: The population of AIDS patients may benefit greatly from the systematic use of subcutaneous venous reservoir due to their clinical and therapeutic characteristics. Nonetheless greater risk of infection may occur in these patients because of the greater need for punctures with respect to the other indications for placement of these catheters. PMID- 8512972 TI - [Enteric fever caused by multiresistant Salmonella typhi: 2 autochthonous cases]. AB - BACKGROUND: References about isolation of strains of Salmonella typhi multiply resistant to antimicrobials and native from Spain are very scant. We describe here two cases of typhoid fever produced by two identical strains of Salmonella typhi. Both strains are multiresistant and autochthonous, judging from epidemiological investigations. METHOD: Microbiological diagnosis was made by means of isolation of causative microorganism from blood and stool, in the first case, and only from stool, in the second one. Antimicrobial susceptibility was ascertained using a minimal inhibitory concentration micromethod. RESULTS: Identification of Salmonella enterica ser. typhi and determination of its resistance to many antimicrobials. Native origin of both strains verified by means of epidemiological investigation. Healing achieved in both cases with ciprofloxacin. CONCLUSIONS: We stand out the rarity of isolating native multiresistant strains of Salmonella typhi in our country, as well as the great epidemiological interest of our finding. We think that diagnosis of these diseases must be made by culturing suitable specimens and isolating causal microorganisms, what will us to determine antimicrobial susceptibility. Finally, we emphasize the resolution of the illness with ciprofloxacin. We consider that this third generation quinolone is a suitable alternative in these cases. PMID- 8512971 TI - [Pulmonary toxoplasmosis. Study of 4 cases and review of the literature]. AB - BACKGROUND: Description of four cases of pulmonary toxoplasmosis and review of the literature. METHODS: A retrospective analysis (October 1990-December 1992) was carried out of the patients with samples of tracheal aspirate, bronchoalveolar lavage (BAL) and lung biopsy positive for T. gondii by immunofluorescence with anti-P30 monoclonal antibodies and cell cultures. RESULTS: Four patients were diagnosed of pulmonary toxoplasmosis, three being immunosuppressed (one renal transplant, one with chronic lymphoid leukemia and one intravenous drug user HIV seronegative) and the remaining one healthy. All the patients developed progressive dyspnea and a radiologic pattern of interstitial pneumonitis (3) or alveolar condensation (1). Three of the patients were cured with pyrimethamine and sulphadiazine. One patient had coinfection by CMV and died. Another 52 cases of this rare condition have been reported in the literature. CONCLUSIONS: In the authors experience, bronchoalveolar lavage material and lung biopsy for T. gondii culture should be performed in immunosuppressed patients with an unclear interstitial radiologic pattern to rule out pulmonary toxoplasmosis. PMID- 8512973 TI - [Clinico-epidemiological study of botulism poisoning in La Rioja (1979-1990)]. AB - BACKGROUND: The aim of the present study was to evaluate botulinic poisoning requiring hospital admission in La Rioja (Spain) during one decade from a clinical-epidemiologic point of view. METHODS: Chart records from patients admitted to the departments of Internal Medicine, Neurology, the ICU, and the Neurophysiology and Preventive Medicine files of the reference hospital between 1979 and 1990 were retrospectively reviewed. RESULTS: Fifteen cases were identified. Home preserves of vegetables were most frequently the foods responsible for the poisoning. The presentation as a sole case constituted half of this series. The most frequent symptomatology was neuro-ophthalmologic and digestive. All the cases were type B. Neurophysiologic studies were compatible with the diagnosis in all the cases in which they were performed. Two cases (13.3%) required intensive care and death occurred in one (6.6%). CONCLUSIONS: a) The habit of home preserves was responsible for the presentation of botulism in this environment. b) Early diagnosis was based on complementary clinical tests together with the neurophysiologic study. c) The mild forms were most frequent. Death in this series was 6.6%. PMID- 8512974 TI - [Capnocytophaga spp. bacteremia in compromised patients]. AB - BACKGROUND: To analyze the clinical characteristics of three patients with Capnocytophaga spp. bacteremia. METHODS: We have review the clinical charts of three patients with Capnocytophaga spp. bacteremia, two patients with acute leukemia and one epileptic patient with chronic alcoholism. RESULTS: All the patients had oral cavity troubles and were treated with different antimicrobial agents. The three patients recovered, one of them requiring changing of the antimicrobial therapy in one of them. CONCLUSIONS: We should be aware of the importance of Capnocytophaga spp. especially in immunosuppressed patients or in other patients with poor dental hygiene and fever. PMID- 8512975 TI - [Rational choice in the use of antibiotics in clinical practice]. PMID- 8512976 TI - [Peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis]. PMID- 8512977 TI - [Keratitis in a contact-lens wearer]. PMID- 8512978 TI - [Furuncular lesion after a tropical journey]. PMID- 8512979 TI - [Bacteremia caused by Vibrio cholerae 0:1]. PMID- 8512980 TI - [A new serotype of Salmonella: Grancanaria]. PMID- 8512981 TI - [Campylobacter jejuni bacteremia and leukocytoclastic vasculitis in a cirrhotic patient]. PMID- 8512982 TI - Antioxidants and cataracts. PMID- 8512983 TI - Biologically based mathematical models of lung cancer risk. PMID- 8512984 TI - Plasma antioxidants and risk of cortical and nuclear cataract. AB - We evaluated nutritional risk factors for cataract in 660 subjects enrolled in the Baltimore Longitudinal Study on Aging. As a part of a regular cycle of visits, nuclear and cortical lens photographs were taken over a 2-year period. Measurements of plasma antioxidants (beta-carotene, ascorbic acid, and alpha tocopherol) were obtained in this cohort as part of the study protocol up to 4 years before lens photographs were taken. We found that plasma beta-carotene and ascorbic acid levels were not associated with risk of nuclear or cortical lens opacities. Higher levels of plasma alpha-tocopherol, however, were associated with a reduced risk of nuclear opacity [odds ratio (OR) for highest quartile vs lowest quartile = 0.52, 95% confidence interval (CI) = 0.27-0.98; OR for middle two quartiles vs lowest quartile = 0.55, 95% CI = 0.30-0.98], after adjusting for age, sex, and history of diabetes. Middle levels of alpha-tocopherol were associated with a reduced risk of cortical opacity (OR = 0.57, 95% CI = 0.32 1.02), but no such association was observed for high levels of alpha-tocopherol. We constructed an index of overall antioxidant status, which indicated that higher levels of plasma antioxidants were not associated with risk of nuclear or cortical opacities. PMID- 8512985 TI - Radon, cigarette smoke, and lung cancer: a re-analysis of the Colorado Plateau uranium miners' data. AB - Much of our knowledge regarding the interaction of radon and tobacco smoke in the etiology of human lung cancer derives from studies of uranium miners. In this article, we present a re-analysis of lung cancer mortality in the Colorado Plateau miners' cohort within the framework of the two-mutation clonal expansion model of carcinogenesis. This analysis takes into account the patterns of exposure to radon and cigarette smoke experienced by individuals in the cohort. A simultaneous re-analysis of the British doctors' cohort indicated that those model parameters relating to the effects of tobacco were comparable in the two data sets. We found no evidence of interaction between radon and tobacco smoke with respect to their joint effect on the first or second stage mutation rates or on the rate of proliferation of initiated cells. The age-specific relative risks associated with joint exposure to radon and cigarette smoke, however, were supra additive but submultiplicative. The analysis also confirmed that fractionation of radon exposures leads to higher lung cancer risks. Finally, we present some estimates of lung cancer risk from environmental radon exposure for non-smokers and smokers. PMID- 8512986 TI - Meta-analysis of epidemiologic dose-response data. AB - We discuss methods for summarizing epidemiologic studies of dose-response. The data from such a study typically appear as a series of dose-specific relative risks, with one category serving as the common reference group. We present methods for estimating the dose-response parameters from single and multiple study reports, for assigning levels to exposure categories when modeling relative risks, and for investigating the effects of study design and subject characteristics on dose-response curves. Finally, we discuss the choice of fixed vs random effects models. We illustrate our points with data from case-control studies of the relation between duration of oral contraceptive use and risk of breast cancer. PMID- 8512987 TI - Risk and rate advancement periods as measures of exposure impact on the occurrence of chronic diseases. AB - The predominant epidemiologic measures of risk factor impact have been various concepts of the "attributable fraction." For many chronic diseases, however, risk factors merely advance the occurrence of disease, and traditional concepts of the attributable fraction do not convey information on the time dimension of premature disease occurrence. Measures of years of disease-free life lost have been proposed to reflect this time dimension but are not always estimable without special assumptions. In this paper, we examine two alternative measures, the risk and rate advancement periods, which are the time periods by which the risk or rate of disease is advanced among exposed subjects conditional on disease-free survival to some baseline age. These measures are applicable for risk factors that promote progression of chronic diseases whose rates increase with age. Point and interval estimates of these measures are easily derived from the output of standard modeling analyses. The measures are illustrated with examples from the literature. The uses and limitations of risk and rate advancement periods are critically discussed. PMID- 8512988 TI - Past use of an intrauterine device and risk of tubal pregnancy. AB - We assessed risk of tubal pregnancy associated with past use of an intrauterine device (IUD). Cases were 256 members of Group Health Cooperative of Puget Sound who experienced a tubal pregnancy between 1981 and 1986. Controls were 666 female members of the Cooperative at risk of ectopic pregnancy who were similar to cases with respect to age and county of residence, but otherwise selected at random. The presence of antibody to Chlamydia trachomatis was assessed in a sample of 134 cases and 182 controls. Women who had previously used an IUD for 3 or more years were more than twice as likely as women who had never used an IUD to have a tubal pregnancy (adjusted relative risk = 2.5, 95% confidence interval = 1.5-4.3). Among these long-term users of an IUD, risk of tubal pregnancy remained elevated for many years after the device was removed. Also, among long-term users, women known to have more than one IUD insertion were no more likely than women with one known insertion to develop a tubal pregnancy. When we restricted our analyses to women who used only copper-containing devices, the results were nearly identical. We conclude that extended past use of an IUD, including use of a copper device, increases the risk of tubal pregnancy. PMID- 8512989 TI - Current use of an intrauterine device and risk of tubal pregnancy. AB - Using data from a population-based, case-control study, we assessed risk of tubal pregnancy associated with use of an intrauterine device (IUD) at the time of conception. Cases were 249 members of Group Health Cooperative of Puget Sound who experienced a tubal pregnancy between 1981 and 1986. Controls were 831 members at risk of ectopic pregnancy who were similar to cases with respect to age and county of residence, but otherwise selected at random. Risk of tubal pregnancy associated with current IUD use was compared separately to that among users of various other (or no) contraceptive methods. Tubal pregnancy was more likely to occur among IUD users than among women using oral contraceptives [relative risk (RR) = 3.8, 95% confidence interval (CI) = 1.5-9.9] or barrier methods (RR = 3.6, 95% CI = 1.6-8.1), or, to a lesser extent, among women who had been surgically sterilized (RR = 1.6, 95% CI = 0.8-3.5). In contrast, IUD users were much less likely to experience a tubal pregnancy (RR = 0.2, 95% CI = 0.1-0.4) than were women who were currently not contracepting. For most women, the decision to use an IUD occurs within the context of choosing among various contraceptive methods. Our results indicate that, for these women, the decision to use an IUD results in increased risk of ectopic pregnancy while the device is in use. PMID- 8512990 TI - Temporal trends in prevalence of cardiovascular malformations in Maryland and the District of Columbia, 1981-1988. The Baltimore-Washington Infant Study Group. AB - We studied the yearly occurrence of isolated cardiovascular malformations in liveborns for the period 1981-1988 in Maryland and the District of Columbia. We used Poisson regression to fit yearly prevalence at birth as a function of time for all cardiovascular malformation case types combined and for three diagnostic subgroups. We give results separately by diagnostic method and race (white/nonwhite), with categories combined when appropriate. Time trends were similar for both races except in pulmonic stenosis diagnosed by echocardiography. The yearly prevalence for all case types, all races, and all diagnostic methods combined increased from 28 to 43 per 10,000 livebirths over the 8 years, due to an increase in the rate among infants diagnosed by echocardiography. For every diagnostic-type-by-race group studied, there were increases in the prevalence for those diagnosed by echocardiography and decreases (or no change in one group) for those diagnosed by cardiac catheterization and/or surgery. Although there may have been an increase in actual occurrence of cardiovascular malformation over our study period, it is also possible that wider use of a new echocardiography technology resulted in increased detection. PMID- 8512991 TI - Application of an event marker in the occupational epidemiologic study of acute irritant symptoms. AB - Field studies of occupational exposure to airborne irritants have predominantly relied on symptom surveys of study participants. As part of a new approach to the study of acute irritant symptoms, subjects exposed to sodium borate dusts recorded their symptom responses at hourly interviews as well as instantaneously on an electronic device called an event marker. Overall, the unprompted marks indicated fewer irritant events than the interviews. Marks were more frequent in the presence of more than one type of symptom and also appeared to reflect more severe symptoms. A proportion of the marked events occurred in time intervals when no symptoms were recalled during the interview. The exposure-response relations were similar regardless of whether they were based on the interview reports or the electronically marked symptoms. The event marker provided a means to examine the time of onset of the acute symptom event. It also made it possible to examine directly the timing profiles of symptom response in relation to changes in exposure levels in a field setting. Despite some inconsistencies, the finding suggests that the event marker may provide an alternative to frequent interviews of exposed workers to obtain irritant symptom responses for exposure response modeling. PMID- 8512992 TI - The hypothesis generating machine. PMID- 8512993 TI - Is there really a conceptual difference in choosing the cutpoint for dichotomizing outcome and predictor variables? PMID- 8512994 TI - Is there really a conceptual difference in choosing the cutpoint for dichotomizing outcome and predictor variables? PMID- 8512995 TI - Epidemiologic theory and societal patterns of disease. PMID- 8512996 TI - Vegetarians and longevity. PMID- 8512997 TI - The effect of a hypoproteic diet and ethanol consumption on the yield of chromosomal damage detected in bone marrow cells of mice. AB - The relationship between protein malnutrition and ethanol consumption as modulating factors of the genetic response to xenobiotics was studied. BALB/c mice of both sexes were fed for three weeks after weaning either with a normal diet containing 25% protein or a hypoproteic diet containing 5% protein. Half of the animals received 20% ethanol in drinking water. Cytogenetic analysis was performed in bone marrow cells. Slides were stained for C-banding in order to assure the accurate scoring of dicentric chromosomes. Results obtained showed an increased frequency of dicentric chromosomes in mice fed with the hypoproteic diet (5.45 dicentrics per 100 cells) in contrast to mice fed with the normal diet (0.61 dicentrics per 100 cells). Ethanol consumption increased the frequency of chromosomal damage, but no differences in the effect of ethanol between mice fed with the normal diet and mice fed with the hypoproteic diet (16.33 and 16.80 dicentrics per 100 cells respectively). The enhanced frequency of dicentric chromosomes in animals fed with the hypoproteic diet might have been originated from the increase or the improper repair of chromosome breaks. The similarity in the response to ethanol consumption in animals fed either with the normal or the hypoproteic diet might have been provoked by a decrease of alcohol dehydrogenase (ADH) level in undernourished mice. The chromosomal damage due to ethanol may be lower in undernourished mice than in mice fed with the normal diet due to the reduced amount of circulating acetaldehyde able to induce chromosomal damage. The results obtained are an evidence of the role played by the diet in the modulation of the genetic response to xenobiotics. PMID- 8512998 TI - Serum hemolytic activity of Babesia gibsoni-infected dogs: the difference in the activity between self and nonself red blood cells. AB - The serum hemolytic activity of Babesia gibsoni-infected dogs varied when assayed with nonself red blood cells from different dogs, whereas it did not vary when assayed with red blood cells, irrespective of self or nonself, from a particular dog throughout the experiment. The variety in activity determined with nonself red blood cells was not related to the type of red blood cell by DEA, D and J systems. Serum hemolytic activity with self red blood cells was different in the course of infection from that with nonself red blood cells, especially in the late stage of infection, when the activity with self red blood cells decreased more rapidly than that with nonself red blood cells. The results indicate that the serum hemolytic activity of B. gibsoni-infected dogs determined with self red blood cells probably reflects the in vivo activity, suggesting that the rapid decrease in activity in the late stage of infection is a way of acquired resistances for the host to recover from hemolytic anemia in the infection. The facts that the hemolytic activity increased by heating the serum at 56 degrees C, that the osmotic fragility of red blood cells remained almost on the same during the course of infection and that Coombs' test for red blood cells of the infected animal was negative suggest that the immune-mediated hemolytic anemia is not a possible mechanism for the progressive and severe anemia in B. gibsoni-infection. The present results support the previous notion that the increased serum hemolytic activity is at least one of the causes of anemia in canine B. gibsoni infection. PMID- 8512999 TI - Effect of fenprostalene 14 days after fertirelin treatment on intervals from treatment to conception in cows with follicular cysts diagnosed by milk progesterone test. AB - Of 170 cows with ovarian cysts which were detected by palpation of the ovaries per rectum, 88 cows (51.8%) were diagnosed as having follicular cysts on the basis of milk progesterone concentrations. Eighty-three of the 88 cows were used for treatment trials. A group of 56 cows injected subcutaneously with fenprostalene, prostaglandin F2 alpha analog, 14 days after treatment with fertirelin, an analog of gonadotropin-releasing hormone, compared with another 27 cows treated only with fertirelin (controls), showed a higher pregnancy rate within 100 days after the initial treatment (66.1 vs 48.1%) and shorter intervals from the treatment to conception (30 +/- 21 vs 43 +/- 27 days). It was concluded that the administration of fenprostalene following fertirelin treatment is effective in shortening the interval from treatment to conception in cows with follicular cysts. PMID- 8513000 TI - Experimental chemonucleolysis with chymopapain in canine intervertebral disks. AB - The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression. PMID- 8513001 TI - Effects of nitroglycerin on hemodynamics in dogs with experimentally inserted heartworms. AB - Hemodynamic effects of nitroglycerin were investigated in dogs with right ventricular failure including engorgement of the pulmonary artery and ascites induced by insertion of adult live heartworms into the pulmonary artery. The mean pulmonary arterial pressure (21.5 +/- 6.6 mmHg) in heartworm-inserted dogs 4 or 5 weeks after heartworm insertion were higher than that of control (4.2-7.1 mmHg). Nitroglycerin administered intravenously at doses of 3 or 10 micrograms/kg decreased pulmonary arterial pressure in these heartworm inserted dogs. This drug also decreased pulmonary vascular resistance and total systemic resistance with no effect on cardiac index and heart rate. PMID- 8513002 TI - Characterization of cultured cells derived from Mongolian gerbil's (Meriones unguiculatus) ascitic malignant melanoma. AB - A cell line was established from a Mongolian gerbil's (Meriones unguiculatus) homotransplantable malignant melanoma. Ascitic tumor cells detected in a gerbil when transplanted intraperitoneally were adapted to culture. In primary culture, cells were divided into 2 types, multipolar and polygonal cells. Cell masses which adhered to polygonal cells were observed after the 6th passage. The adhering cells were removed and transferred into another flasks. The cells showed multipolar and possessed projections. Then after, the cells increased in number vigorously and formed acinous structures. At early passages, abundant melanin granules in some of the cells were demonstrated by light and electron microscopical observations. Most of the cells were positive by DOPA reaction. Melanin pigments were gradually decreased through the 20th to 30th passage and most of cells became amelanotic. The doubling time of the cell line was 32 hr. Chromosome number of the cell line ranged from 68 to 82. Whitish tumors were produced in the abdominal cavity within 30 days when intraperitoneally inoculated the cells to gerbils. This cell line, designated as MGM-A, has been subcultured for more than 100 passages during 2 years. PMID- 8513003 TI - Effect of trypsin treatment of in vitro fertilized bovine embryos on their subsequent survival and development. AB - The object of this study was to determine whether several washings with trypsin affected the survival and development of in vitro fertilized (IVF) bovine embryos. The embryos developed to blastocysts 7-8 days after insemination, were washed 12 times in washing medium (modified Dulbecco's phosphate-buffered saline (mPBS) containing 20% fetal bovine serum (FBS): 25 mM Hepes TCM199 with Earle's salts = 1:1), or in a series of three washes in the washing medium, two in mPBS containing 0.3% bovine serum albumin (BSA), two in 0.25% trypsin in Hank's solution (without Ca++ and Mg++) for a total time in the trypsin of 60 to 90 sec and five in the washing medium. After washing, the embryos were either cultured in vitro or cryopreserved. The fresh and frozen-thawed embryos were either cultured for 72 hr in vitro for evaluating development or transferred nonsurgically to recipient cows. Development of fresh and frozen-thawed embryos in vitro in control-washed and trypsin-washed embryos did not differ. Pregnancy rates did not differ (P > 0.05) among recipient cows receiving control-washed or trypsin-washed embryos, and transferring fresh or frozen-thawed embryos. These results indicate that the treatment of bovine IVF embryos with trypsin during washing did not have a positive effect on embryonic development. PMID- 8513004 TI - Spontaneous histogenic tumors of epididymis observed in B6C3F1 mice. AB - Four primary histiogenic tumors of the epididymis were discovered in 110 male B6C3F1 mice used in a carcinogenicity study in our laboratory. From the results, all these tumors were considered to be spontaneous. Histologically, the tumors were characterized by compact growth of spindle to oval shape histiocytic cells with or without a cleaved nucleus. Focal hemorrhage was present in three cases, and erythrophagocytosis occurred in such lesions. The tumors had some similar histological features of histiocytic sarcomas, which had been observed with high malignancy in other male and female animals. However, systemic growth and atypsim of neoplastic cells found in the histiocytic sarcomas were not observed in these epididymal tumors. On the other hand, four histiogenic tumors of the uterus, with features characteristic of epididymal tumors, were observed in 106 female mice. The uterine histiogenic tumors were regarded as benign or precursor lesions of histiocytic sarcoma. Furthermore, it is suspected that histiocytic sarcoma arises from the epididymis. PMID- 8513005 TI - Differential effects of footpad stimulation on the monosynaptic reflex in the spinalized cat. AB - Experiments were performed in 17 adult cats spinalized at T10-11. The effects of electrical stimulation of the central pad (CP) and toe pads (TP-2, 3, 4, 5) on the monosynaptic reflex (MR) in lumbar spinal segments were studied. The conditioning stimulation had different effects on the MRs of the various motoneurons except the posterior biceps and semitendinosus, depending on the footpad stimulated. Lateral gastrocnemius and soleus, and medial gastrocnemius (MG) MR were inhibited by footpad stimulation. The effect of TP-2 (medial footpad) stimulation on MG-MR was weak. The popliteus (Pop) and tibialis anterior muscles (TA) are inward and lateral rotators of the knee joint, respectively. Pop and TA-MR were excited by stimulation of lateral and medial TPs, respectively. Plantaris MR was enhanced and inhibited by stimulation of the CP and TPs, respectively. There were remarkable differences in the effects of TP conditioning stimulation on the flexor digitorum longus, extensor digitorum longus, peroneus brevis and tertius, and peroneus longus-MRs, depending on the toe pads stimulated. These results suggest that afferent inputs from footpads modulate the activity of motoneurons, stabilize the foot and help maintain body balance. PMID- 8513006 TI - Effects of active egg white product on neutrophil function in calves. AB - The effects of an active egg white product (AEWP) on neutrophil function in calves were investigated. Calves were administered AEWP orally at doses of 250 mg and 500 mg/kg either once or twice, with an interval of 5 days between doses in the latter case. The peripheral blood neutrophils of calves receiving a single 500 mg/kg dose displayed increased nitroblue tetrazolium reducing activity and increased intracellular killing of Staphylococcus aureus from 1 day after administration, with maximum levels being attained on the 3rd day. However, no such increase of these activities was observed after administration of 250 mg/kg. Calves receiving two doses of 500 mg/kg displayed the same changes as seen in the corresponding one-dose group, while the neutrophil activity of calves receiving 250 mg/kg also increased after the second dose. However, no increase in the peripheral blood neutrophil count was observed after AEWP administration. Thus, AEWP enhanced the nonspecific antibacterial activity of neutrophils when given to calves by the oral route. PMID- 8513007 TI - Isolation and identification of canine plasma components suspected as uremic toxins. AB - Suspected uremic substances contained in four fractions, which had been selected as the suspected canine uremic peaks in the previous study, were isolated by two stages of preparative liquid chromatography (PLC) from plasma of uremic dogs treated with the ligation of the ureter, and then their physicochemical properties were examined. The primary separation of the suspected uremic peaks were performed with the same anion exchange resin as used in the analytical HPLC in the previous study. Analytical reverse phase HPLC showed that three of 4 suspected uremic peaks almost consisted of single substances, but the other contained several substances. Main subfractions of these peaks were successfully isolated by the secondary stage reverse phase PLC. By means of thin layer chromatography, ultraviolet absorption spectrometry and proton-nuclear magnetic resonance spectroscopy, components of 4 main peaks were confirmed to be small molecules such as a pyridine derivative, uric acid, hippuric acid and kynurenic acid, respectively. PMID- 8513008 TI - Monitoring bovine embryo viability with early pregnancy factor. AB - The viability of the bovine embryo was monitored by measuring the early pregnancy factor (EPF). The EPF activity was measured by the rosette inhibition test before and after artificial insemination (AI) at natural estrus (n = 14), and after superovulatory treatment followed by embryo removal on day 7 after AI (n = 5). In the cows inseminated artificially at natural estrus, there were significant differences (p < 0.01) in the rosette inhibition titer (RIT) between pregnant and non-pregnant cows on day 13-16 and day 20-25 after AI. In the 8 pregnant cows, the RIT remained more than 5 from day 6-9 after AI. In the 6 non-pregnant cows, two patterns were observed. In one pattern, RIT rose transiently to more than 5 and decreased to less than 4 thereafter. In the other pattern, RIT remained less than 4 throughout the experimental period. The former pattern suggested early embryonic death, while the latter suggested that fertilization had not taken place or that early embryonic death had occurred before the first blood collection on day 6-9 after AI. In the cows superovulated followed by embryo removal on day 7 after AI, the RIT values were all less than 4 on the day of AI (day 0), rose to more than 5 on day 3 and thereafter then until the day of embryo removal on day 7. In 4 cows, the RIT decreased to less than 4 by 3 days after embryo removal, and in the remaining one cow, the RIT decreased to less than 4 by 7 days after embryo removal. These findings suggest that the measurement of EPF activity is useful for monitoring the viability of bovine embryos. PMID- 8513009 TI - Blood gas analysis in dogs with pulmonary heartworm disease. AB - Blood gases were analyzed in dogs with pulmonary heartworm (HW) disease. The arterial oxygen tension (PaO2) in dogs with mild signs of dirofilariasis (mildly affected group, n = 48, 85.7 +/- 8.2 mmHg) and in dogs with signs of right heart failure (severely affected group, n = 13, 76.4 +/- 11.6 mmHg) was lower (p < 0.01) than in dogs without HW infection (HW-free group, n = 19, 91.5 +/- 7.3 mmHg). Only 2 dogs in the severely affected group had a PaO2 less than 60 mmHg. The arterial carbon dioxide tension (PaCO2, p < 0.01) and mixed venous O2 (p < 0.01) and CO2 (p < 0.01) tensions were lower, and alveolar-arterial oxygen difference (AaDO2, p < 0.01) was greater in the severely affected group than in the HW-free and mildly affected groups. Arterial pH and bicarbonate (HCO3-) concentrations were lower (p < 0.01) in both affected groups than in the HW-free groups. The anion gap level was not different among the 3 groups. Serum lactic acid level in the severely affected group was higher (p < 0.01) than in the HW free and mildly affected groups. However, a slightly higher serum lactic acid concentration was found only in 2 dogs of the severely affected group (3.84 mmol/l and 3.82 mmol/l). The PaO2 (r = -0.62) and AaDO2 (r = 0.66) correlated significantly (p < 0.01) with mean pulmonary arterial pressure. One week after HW removal, blood gases, pH and HCO3- concentration remained unchanged in the mildly affected group. In the severely affected group, blood gas values were the same, but pH and HCO3- concentration improved slightly. PMID- 8513010 TI - A novel response of anion transporter in equine erythrocytes to a fluorescent substrate, N-(2-aminoethyl sulfonate)-7-nitrobenz-2-oxa-3-diazole (NBD-taurine). AB - This report describes a unique response of the anion transporter in equine erythrocytes to the fluorescent substrate N-(2-aminoethyl sulfonate)-7-nitrobenz 2-oxa-3-diazole (NBD-taurine). Equine erythrocytes showed fluxes of NBD-taurine both inward and outward at rates considerably slower than those in human cells. These fluxes were completely abolished by a typical anion transport inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonate. Furthermore, NBD-taurine competitively inhibited the uptake of phosphate in equine red cells with an inhibition constant of phosphate that was slightly higher than the Michaelis constant of phosphate uptake. These results demonstrate that the anion transporter (band 3) in equine red cells binds NBD-taurine but does not prefer it as the substrate for transport, suggesting a structural difference between equine and human anion transporters at the polypeptide portion which is implicated in anion transport. PMID- 8513011 TI - Luminol-dependent chemiluminescence of hemocytes derived from marine and estuarine molluscs. AB - Hemocytes of two marine molluscs, Nerita albicilla (gastropod) and Mytilus edulis (bivalve), were stimulated in vitro with zymosan and live cells of Vibrio parahaemolyticus and Escherichia coli as determined by luminol-dependent chemiluminescence (CL). The CL response was enhanced in the presence of the respective molluscan plasma. Hemocytes of an estuarine gastropod, Clithon retropictus, showed low CL response to zymosan and V. parahaemolyticus, which was slightly enhanced in the presence of C. retropictus plasma. Hemocytes of an estuarine bivalve, Corbicula japonica, showed no CL response. CL response of hemocytes might be a useful tool to analyze defense mechanisms of estaurine molluscs. PMID- 8513012 TI - Effect of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products of cats. AB - The effects of lactosucrose (4G-beta-D-galactosylsucrose) on fecal flora and fecal putrefactive products were studied in 3 Himalayan and 5 Persian cats fed 175 mg of lactosucrose/each/day for 2 weeks. During lactosucrose administration, the counts of lactobacilli increased significantly (p < 0.05), whereas the counts of clostridia, including Clostridium perfringens and Enterobacteriaceace decreased significantly (p < 0.05). The levels of fusobacteria and staphylococci were decreased significantly (p < 0.01) on day 7 of lactosucrose administration, while the counts of bacteroides increased significantly (p < 0.05) and day 14 of lactosucrose administration compared to pre-administration. In frequency of occurrence, bifidobacteria increased significantly (p < 0.001) during lactosucrose administration, while Spirochaetaceae and lecithinase-negative clostridia decreased significantly (p < 0.05) on day 14 of lactosucrose administration compared to pre-administration. No detectable change occurred in the counts of other organisms throughout the experimental periods. Fecal concentrations of ammonia, indole, ethylphenol, and urinary ammonia were reduced significantly (p < 0.05) on day 14 of lactosucrose administration. The water content and weight of the feces increased slightly during lactosucrose administration, but the pH values decreased slightly. The environmental ammonia and the fecal odor also decreased remarkably (p < 0.01) during administration. PMID- 8513013 TI - Characteristics of Staphylococcus aureus isolated from peracute, acute and chronic bovine mastitis. AB - Fifty-eight Staphylococcus aureus strains isolated from bovine mastitic milk at 27 dairy farms in Japan during the period from November 1988 to May 1989 were examined for their productivity of virulence associated factors. The positive rates of the total isolates for various virulence factors were as follows: toxic shock syndrome toxin-1 (TSST-1, 27.6%), staphylococcal enterotoxins (SEs, 34.5%), alpha-haemolysin (74.1%), beta-haemolysin (65.5%), delta-haemolysin (12.1%), DNase (100%), egg-yolk factor (25.9%), clumping factor (70.7%) and protein A (58.6%). All of S. aureus isolates from peracute mastitis produced TSST-1, SEC, alpha-haemolysin and beta-haemolysin. While none of clumping factor and protein A were detected among peracute isolates, these factors were produced at a relatively high frequency by isolates from chronic mastitis. In coagulase typing, the most predominant type was VI (36.2%), and types IV, V and VIII were not observed. TSST-1 positive isolates showed interesting characteristics which all of the isolates produce both SEC and coagulase type VI but lack egg-yolk factor, clumping factor and protein A except for one isolate. We could infer that TSST-1 and SEC contribute to bovine mastitis, especially to peracute mastitis from the present study. PMID- 8513015 TI - An attempt to estimate the pulmonary artery pressure in dogs by means of pulsed Doppler echocardiography. AB - The pulmonary artery blood flow was determined in 40 dogs by pulsed Doppler echocardiography as a non-invasive means for estimating pulmonary artery pressure. Most of these dogs had become infected with heartworm disease which has been known to often cause pulmonary artery hypertension. From the flow velocity profile, four parameters, i.e., the Doppler tracing pattern, right ventricular ejection acceleration time (AT), and the ratios of AT to heart rate (AT/HR) and right ventricular ejection time (AT/ET), were obtained and their correlations with the pulmonary artery pressure determined invasively were investigated. Although the morphological pattern of flow velocity hardly allowed quantitative estimation of the pulmonary artery pressure, a relatively good negative correlation (P < 0.01) was obtained between the systolic pulmonary artery pressure and AT (r = 0.71), AT/HR (r = -0.67) or AT/ET (r = -0.84). The present results indicate that pulsed Doppler echocardiography is applicable to the estimation of pulmonary artery pressure and that AT/ET has the closest correlation with directly measured pulmonary artery pressure. PMID- 8513014 TI - Testicular disruption in the As (aspermia) mutant rat, with special reference to the aggregate of ribosomes. AB - The morphology of the testis of the mutant As (aspermia) strain rat with severely interrupted spermatogenesis was investigated in the present study. The most advanced development in spermatogenesis was observed at the step 8 at which spermatids had basally-oriented acrosomes. Multinucleate giant cells derived from round spermatids were frequently encountered within the seminiferous tubules. The functionally normal status of the blood-testis barrier between adjacent Sertoli cells was confirmed by morphological and lanthanum tracer studies. By light microscopy, a peculiar structure was found within the pachytene spermatocyte, consisting of numerous particles of approximately 25 nm in diameter. By histochemical and electron microscopic studies, this structure was identified as an aggregate of ribosomes. Neither immature spermatogenic cells up to the pachytene phase, nor Sertoli cells nor interstitial regions showed a recognizable abnormality. It seems that the testicular disruption in the As mutant rat is due to the abnormality in the protein synthetic pathway in pachytene spermatocytes. PMID- 8513016 TI - Proto-oncogene of genomic DNA, related to the human epidermal growth factor receptor (EGFR) gene, from clinically normal domestic animals. AB - Genomic DNAs of cattle, horses, pigs, dogs, cats and chickens were surveyed using Southern blot hybridization analysis, with a human EGFR cDNA fragment. Several bands with different numbers and molecular weights were observed under the condition of low stringency in the individual animal species. The bands showing DNA polymorphism were observed among bovine genomic PstI-digested DNAs from 4 individuals and EcoRI-digested genomic DNAs from 4 chickens. These results may provide basic data which are useful for analysis of tumorigenetic mechanisms in domestic animals. PMID- 8513017 TI - Isolation and identification of mycoplasma strains from various species of wild rodents. AB - Attempts were made to isolate mycoplasmas from respiratory and urogenital tracts of 35 apparently healthy wild rodents comprising 7 species under 4 genera. Mycoplasmas were isolated from nasal and oral cavities, tracheas, vaginas and penises of the wild rats: ricefield rats (Rattus argentiventer), roof rats (R. rattus) and Polynesian rats (R. exulans), but none was isolated from brown rats (R. norvegicus), house mice (Mus musculus), smithi's voles (Eothenomys smithi) and soft-furred field rats (Millardia meltada). These mycoplasma strains were identified as Mycoplasma pulmonis and M. arthritidis on the basis of their biological and serological properties. PMID- 8513018 TI - Direct ABC immunohistochemistry to Encephalitozoon cuniculi. AB - Among the sera from 9 rabbits spontaneously infected with Encephalitozoon cuniculi, a serum which revealed a high titer for E. cuniculi by indirect protein A-gold (IPAG) immunohistochemistry and reacted with the outer layer of the shell of E. cuniculi spores on immunoelectron microscopical examination, was biotinylated. The biotinylated rabbit anti-E. cuniculi IgG reacted immunohistochemically with E. cuniculi, but not with other protozoa tested, namely Neospora caninum, Toxoplasma gondii and sarcocystis. The direct avidin biotin-peroxidase complex (ABC) immunohistochemistry using biotinylated rabbit anti-E. cuniculi IgG in this study is a useful tool for the diagnosis and study of encephalitozoonosis. PMID- 8513019 TI - Contact microradiographic analysis of feline tooth resorptive lesions. AB - Feline tooth resorptive lesions were studied using contact microradiographic analysis of ground sections. Contact microdiagram films were developed with a PIAS-imaging device, and decalcification patterns were evaluated, revealing a clear boundary between normal tissue and the resorptive area, which was different from the image of dental caries in humans. By contrasting analysis, decalcification signs appearing in human caries were not observed in feline resorptive lesions. PMID- 8513020 TI - Seroepidemiological survey of chlamydial infections in light horses in Japan. AB - To investigate the overall prevalence of chlamydial infections in light (i.e. non draught) horses in Japan, 599 sera obtained from 12 localities in 1991 were tested for complement fixation antibodies. The mean antibody positive rates of the all sera were 15.2% (91/599) and the regional positive rates were higher in Honshu (19.1%, 48/251) and Kyushu (20.0%, 20/100) than in Hokkaido (9.3%, 23/248). In Honshu, the highest rate (56.0%, 28/50) was observed in Utsunomiya. Analysis of the positive rate in different age groups showed that the 2-5 years age-group had the highest prevalence of chlamydial infections. This indicates that chlamydial infection is prevalent in light horses in Japan. PMID- 8513021 TI - Isolation of Trichophyton verrucosum from lesional and non-lesional skin in calves. AB - Trichophyton verrucosum, a causative agent of bovine dermatophytosis in Japan is considered to transfer easily from infected cattle to other healthy ones. No studies have ever tried to elucidate the distribution of T. verrucosum in breeding environment. In this study, we investigated the distribution of T. verrucosum in infected young calf skin and healthy skin. Hairs or scale samples were collected from 29 lesional skin, and 46 non-lesional skin of the 19 and 34 infected calves, respectively, both varying in age 2 to 6 months old, and 35 hair samples from the 29 healthy ones. They were directly inoculated on medium. The detection rates of T. verrucosum-positive were 58.6% from the lesional parts, 34.8% from the non-lesional parts and 17.1% from the healthy parts. The isolation of T. verrucosum from the calves with no skin lesion due to dermatophytosis implied that this infection might be easily transmitted by the contact with the infected calves. T. verrucosum infection in cattle poses a serious problem in animal husbandry. It is also important for public health to take preventive measures against the infection. PMID- 8513022 TI - In vitro cultivation of the third and fourth stage larvae of Angiostrongylus cantonensis. AB - The third and fourth stage larvae of Angiostrongylus cantonensis were cultured in various media. When the third stage larvae were cultured in RPMI 1640 supplemented with 20% fetal calf serum for four weeks, about 30% developed to the late third stage. On the other hand, when the fourth stage larvae recovered from rat brains were cultured in Waymouth's chemically defined medium (MB 752/1) for one week, the worms grew rapidly and 74% developed into young adults. The mean body length of the worms in Waymouth's medium showed a 1.4-fold increase in size compared with that before culture. PMID- 8513023 TI - Detection of plasmid DNA in Erysipelothrix rhusiopathiae isolated from pigs with chronic swine erysipelas. AB - Forty-three strains of Erysipelothrix rhusiopathiae, isolated from pigs with chronic swine erysipelas, were examined for the presence of plasmid DNA by agarose gel electrophoresis and electron microscopy. Seven of these strains were found to contain plasmids of which number were varied from 1 to 6. The plasmids ranged from 1.4 to 86 kb in size. This is the first reported evidence for plasmid DNA in E. rhusiopathiae. The functions of the plasmids are unknown at present. PMID- 8513024 TI - Displacement of bilirubin from albumin by berberine. AB - A study was made of the effect of berberine, the major ingredient of the Chinese herb huanglian (coptis chinensis) reported to pose some risk for kernicterus among jaundiced newborn Chinese infants, on the protein binding of bilirubin, using the peroxidase kinetic method. Berberine was found in vitro, as to its displacing effect on a molar basis, to be about tenfold superior to phenylbutazone, a known potent displacer of bilirubin, and about hundredfold to papaverine, a berberine-type alkaloid. The chronic intraperitoneal administration of berberine (10 and 20 micrograms/g) daily for 1 week to adult rats (mixed breed of Wistar and Sprague-Dawley) resulted in a significant decrease in mean bilirubin serum protein binding, due to an in vivo displacement effect and a persistent elevation in steady-state serum concentrations of unbound and total bilirubin, possibly due to inhibition of metabolism. The use of the herb and other traditional Chinese medicines containing a high proportion of berberine is best avoided in jaundiced neonates and pregnant women. PMID- 8513025 TI - Effect of skinfold thickness on transcutaneous bilirubin measurements. AB - We studied the effect of skinfold thickness on the correlation between serum total bilirubin level and transcutaneous bilirubin (TcB) readings. Skinfold thickness measurements were taken at 1-4 h of age. Serum total bilirubin levels and TcB readings were obtained at 1-4 (first) and 44-56 h of age (discharge). No correlation was found between first reading and skinfold thickness (rho = 0.196), whereas correlations with first serum bilirubin level and blood hematocrit were 0.397 and -0.373, respectively. The correlation between discharge serum total bilirubin level and TcB reading was affected by skinfold thickness, and not improved with the use of first reading as a reference for discharge reading. PMID- 8513026 TI - Effects of birthweight status and gestational age on the quality of general movements in preterm newborns. AB - It is hypothesised that individual differences in nervous system functioning, undetected by a neurological examination, are reflected in the quality of spontaneous movements of preterm newborns. Given this hypothesis it is expected that a short pregnancy duration and IUGR will be related to an abnormal movement quality. These expectations were confirmed in a group of 37 small-for-gestational age and appropriate-for-gestational-age preterm newborns with gestational ages ranging from 27 to 34 weeks without serious perinatal complications and for whom no overt neurological abnormalities could be detected based on the evaluation of elicited responses and tonus at the postmenstrual age of 35 weeks. The quality of general movements was adversely affected by both IUGR and a pregnancy duration below 32 weeks. Newborns with an abnormal movement quality also had significantly lower obstetrical optimality scores. Previous research has shown these scores to be related to the neurological condition of the newborn. We conclude that observations of movement quality, being neither intrusive nor time consuming, may constitute a useful addition to the neurological assessment of preterm newborns without serious perinatal complications. PMID- 8513027 TI - Prevalence and toxigenicity of Clostridium difficile isolates in fecal microflora of preterm infants in the intensive care nursery. AB - Fecal isolates of Clostridium difficile and its toxin B were followed prospectively in 50 preterm intensive care nursery (ICN) patients. The first stool specimen was obtained after 1 week of enteral feeding, at 15 +/- 1 days of life, and 2 more specimens were collected at 2-week intervals, 24 +/- 1 and 32 +/ 2 days of life. The stools were cultured for C. difficile, and tested for C. difficile toxin B. In the first specimen 15% of stools grew C. difficile. In the second specimen C. difficile isolation rates increased to 33% and plateaued. Toxin B was detected in 71, 93 and 100% of culture-positive stools in the first, second, and third specimens, respectively. C. difficile colonization was not associated with a higher incidence of necrotizing enterocolitis or diarrhea, and using precollected, frozen human milk did not protect from C. difficile colonization. PMID- 8513028 TI - Low-density lipoprotein catabolism does not respond to estrogen in the fetal and newborn rat. AB - The elimination of native and methylated low-density lipoprotein (LDL) from serum and the effect of estradiol on the serum LDL-apoB pool, the uptake of homologous [125I]-LDL into liver and adrenals, and the fractional catabolic rate (FCR) of [125I]-LDL was studied in fetal (22nd day of gestation), newborn (15th day postpartum), and adult rats. In fetal rats the receptor-mediated LDL decay accounted only for 47%, whereas in adults it was calculated to 65%. In the latter, estrogen caused (1) a diminution of the serum LDL-apoB pool by 85%; (2) an enhancement of the LDL uptake into the liver and the adrenals by 5- and 10 fold, respectively, and (3) an acceleration of the [125I]-LDL decay in the serum with a rise of the FCR by 3-fold. In contrast, neither the LDL pool and uptake nor the LDL elimination (FCR) did respond to estrogen in fetal and newborn rats. In summary, the LDL catabolism of the rat is insensitive towards estrogen in the late gestational period and during the first 2 weeks of postnatal life [3]. PMID- 8513029 TI - Influence of the destabilisation of the maternal digestive microflora on that of the newborn rat. AB - By destabilising the digestive flora of pregnant rats by antibiotic treatment, it was shown that part of the digestive microflora of the neonate originated from the maternal faeces. A mixture of ampicillin, bacitracin neomycin and streptomycin associated with nystatin were administered ad libitum at three different times, 1-3, 3-5, and more than 5 days before the estimated date of littering. For each treatment, samples were taken from the faeces, teats, and vagina of dams and from the digestive tracts of neonates aged between 6 and 120 h, and analysed for the presence of staphylococci, enterococci, lactobacilli and coliform bacteria. Antibiotic treatment reduced digestive flora populations to levels lower than 10(2) g-1 but had less effect on the vaginal and cutaneous mammary flora. In the digestive microflora of the neonate, the enterococci were unevenly affected, whereas the staphylococci were considerably decreased and the lactobacilli almost completely eliminated; coliform bacteria were found sporadically and in small numbers. The traces of antibiotics found in milk are not sufficient to explain these modifications. Counts made in control animals on media fed the same antibiotic concentrations were not modified. This work underlined the awful consequences for the newborn of a serious perturbation of the mother flora and the necessity of its presence for a normal installation of the digestive microflora of the newborn. PMID- 8513030 TI - Perinatal development of Brunner's glands in the rat: morphometrical study. AB - Perinatal changes of the Brunner's glands in rats from fetal day 20 through neonatal day 3 were studied morphometrically and electron-microscopically. Percentage volume of secretory granules of the gland cells did not change from fetal day 20 through neonatal day 1 and increased significantly from neonatal days 1-2; this level was maintained through neonatal day 3. Electron microscopically, the gland cells during the fetal days were rich in free ribosomes. The Golgi apparatus and rough-surfaced endoplasmic reticulum (RER) were poorly developed during fetal days. After birth, however, the cells showed active formation of secretory granules, which was evidenced by well-developed Golgi apparatus, distended RER and accumulation of granules in the apical cytoplasm. Furthermore, light microscopy revealed that strongly PAS-positive material increased for the first time after birth, indicating remarkable formation of the secretory granules. Thus, the present study indicates that the cell of the Brunner's glands become active in secretory granule formation just after birth by responding to ingested material following birth. PMID- 8513031 TI - Developmental changes in the erythrocyte metabolism in bandicoot Isoodon macrourus. AB - Activities of 13 different enzymes were measured in the erythrocytes of juvenile and adult bandicoots, Isoodon macrourus. Seven of these enzymes had significantly (p < 0.05 or less) greater activities in the juveniles compared to the adult animals. The activity of one enzyme--phosphofructokinase--was significantly (p < 0.01) lower in the juveniles. However, the activity of NADH-methaemoglobin reductase (MR) was similar in the two groups of animals. The rates of lactate production using four different substrates (glucose, galactose, inosine and adenosine) were also higher in the juveniles. These results indicate that the erythrocytes of juvenile bandicoots are metabolically more active than those of the adult animals and follow the general pattern of higher metabolic activity in the young red cells in eutherian mammals, with possible exception of NADH-MR activity. PMID- 8513032 TI - Criteria for rationally evaluating animal models of posttraumatic stress disorder. AB - Animal models of stress have the potential to provide information about the course and etiology of posttraumatic stress disorder (PTSD). To date, however, there have been no systematic approaches for evaluating the relevance of animal models of stress to PTSD. It has been established in the animal literature that different types of stress paradigms lead to different biobehavioral consequences and that many different factors contribute to differential responsivity to stress. It becomes important therefore to differentiate between factors that are essential to the induction of PTSD-like symptoms and those that influence their manifestations. In the present commentary, we present five criteria that must be fulfilled by animal models of stress for them to be useful to understanding the induction of PTSD. We then evaluate two potential animal models of stress- inescapable shock-learned helplessness and time-dependent sensitization--to illustrate how to more successfully pair animal models of stress with the specific clinical syndrome of PTSD. PMID- 8513033 TI - Single-photon emission computed tomography with 99mTc-exametazime in unmedicated schizophrenic patients. AB - We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined. PMID- 8513034 TI - Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: a SPECT study. AB - Using single photon emission computed tomography (SPECT) and 99mTc hexamethylpropyleneamine oxime (HM-PAO), we assessed brain perfusion in seven patients with panic disorder (PD) and in five age-matched normal subjects at rest. No patient had ever received drug treatment for panic. All patients were sensitive to lactate-induced panic. Computed tomography (CT) scans did not reveal any morphological abnormalities of the brain in any of the PD patients. Two indices of cerebral perfusion were calculated; these demonstrated alterations of brain perfusion in the PD group. Significant right-left asymmetry was found in the inferior frontal cortex of the PD patients. We also observed a significant blood flow increase in the left occipital cortex and a significant decrease in the hippocampal regions bilaterally. Although the changes seen in the inferior frontal cortex and occipital cortex may be related to anxiety experienced by the patients during the study, the pattern of hippocampal hypoperfusion appears to be characteristic of panic disorder. This suggests that the hippocampal structures may play an important role in the pathophysiology of panic disorder. PMID- 8513035 TI - Impairment of early cortical processing in schizophrenia: an event-related potential confirmation study. AB - Abnormalities of auditory information processing represent a core feature of schizophrenic psychopathology. Event-related potentials (ERP) provide an objective index of the information processing deficits associated with schizophrenia and a tool for investigation of the underlying pathophysiology. The best established abnormality is a decrease in the amplitude of auditory P300. In an "oddball" paradigm, P300 is preceded by a series of earlier, negative-polarity ERP components that index discrete, prior information-processing events. The earliest such component, mismatch negativity (MMN), is elicited whenever a deviant, "oddball" stimulus interrupts a sequence of repetitive standard stimuli. MMN is generated principally within primary auditory cortex or adjacent structures on the superior temporal plane, suggesting that it indexes the earliest cortical event in the cognitive processing of auditory information. In the present study, MMN was studied in a group of 14 chronic schizophrenic subjects relative to 12 age- and IQ-matched normal controls in a passive auditory oddball paradigm in order to test the hypothesis that auditory information processing is impaired in schizophrenia, even at the level of primary sensory cortex. Schizophrenic subjects showed a significant reduction in MMN amplitude relative to controls, with a trend toward a greater deficit on the left than the right side. The finding of impaired MMN generation in schizophrenia suggests that information processing is impaired even at the level of auditory cortex and that the pathophysiological processes underlying information processing dysfunction in schizophrenia are widespread throughout the cortex, rather than limited to high order association cortex such as prefrontal or mesial temporal cortex. PMID- 8513036 TI - Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. AB - Protein kinase C (PKC) activity and PKC translocation in response to serotonin were investigated in platelets obtained from bipolar affective disorder subjects before and during lithium treatment. Ratios of platelet membrane-bound to cytosolic PKC activities were elevated in the manic subjects. In addition, serotonin-elicited platelet PKC translocation was found to be enhanced in those subjects. Lithium treatment for up to 2 weeks resulted in a reduction in cytosolic and membrane-associated PKC activities and in an attenuated PKC translocation in response to serotonin. These preliminary results suggest that alteration in platelet PKC is associated with the manic phase of bipolar illness. The results also suggest that lithium treatment reduces the sensitivity of platelets to PKC translocation induced by activation of serotonin-2 receptors. PMID- 8513037 TI - A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. AB - This study investigated the efficacy of oral melatonin in alleviating jet lag in flight crew after a series of international flights. The optimal time for taking melatonin in this group was also investigated. In a double-blind placebo controlled trial, 52 international cabin crew were randomly assigned to three groups; early melatonin (5 mg started 3 days prior to arrival until 5 days after return home); late melatonin (placebo for 3 days then 5 mg melatonin for 5 days); and placebo. Daily ratings showed a trend in jet lag, mood, and sleepiness measures toward an improved recovery in the late melatonin group and a worse recovery in the early melatonin group as compared to placebo. Retrospective ratings made 6 days after arrival showed the late melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness than the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin may have potential benefits for international aircrew. PMID- 8513038 TI - Prolactin response to fenfluramine and placebo challenge following maintenance pharmacotherapy withdrawal in remitted depressed patients. AB - Plasma prolactin (PRL) response to fenfluramine (FF) (60 mg orally) and placebo challenge was examined in eight remitted depressed patients who were withdrawn for 14 days from maintenance pharmacotherapy with clomipramine (CMI) plus lithium carbonate (Li) (n = 6) or Li alone (n = 2), 6 months after recovering from their major depressive episode. The patients had undergone identical FF challenge tests while drug free prior to commencing treatment with electroconvulsive therapy (ECT) (n = 4) or CMI supplemented with Li (n = 4) and after completing the above treatments. PRL response to FF in the remitted, drug-free state was significantly enhanced compared to the response prior to treatment (while depressed and drug free) and not significantly different from the response following treatment with ECT (n = 4) or CMI plus Li (n = 4) 6 months before. Other work of a similar nature supports the view that enhanced serotonergically mediated hormone release in drug-withdrawn, remitted depressives, represents a long-standing change in central serotonergic responsiveness and not a continued effect of antidepressant treatment or a manifestation of medication withdrawal. PMID- 8513039 TI - Physostigmine ameliorates the delusions of Alzheimer's disease. AB - Alzheimer's disease (AD) patients frequently manifest delusions, and the cholinergic deficiency of AD may contribute to this aspect of the psychopathology of the disorder. In a double-blind, crossover study involving two patients, we compared the antidelusional efficacy of physostigmine, an acetylcholinesterase inhibitor, with haloperidol, a widely used neuroleptic agent. Physostigmine ameliorated the delusions and produced fewer side effects. These preliminary observations suggest that the cholinergic deficiency contributes to the occurrence of delusions in AD and cholinergic therapy may have a role in the treatment of the delusional symptoms. PMID- 8513040 TI - Valproate treatment of panic disorder and lactate-induced panic attacks. AB - Several lines of evidence suggest that the anticonvulsant drug valproate may have antipanic properties: (1) It enhances gamma-aminobutyric acid activity in the brain; (2) it has anxiolytic effects in animal models of anxiety; and (3) it has been reported to be effective in panic disorder in several preliminary studies; however, valproate has not been studied in the prevention of lactate-induced panic attacks. Sixteen patients with panic disorder underwent a lactate infusion followed by a 28-day treatment period with valproate and subsequent rechallenge with lactate. Response was measured by change in panic attack frequency and Hamilton Anxiety Scale (HAS) scores and by the ability of valproate to block lactate-induced panic on rechallenge. Of the 14 patients completing the 28-day trial, 10 (71%) experienced a greater than 50% reduction in the weekly frequency of panic attacks. Six (43%) had complete remission. HAS scores dropped significantly from a baseline mean of 30.8 +/- 9.4 (SD) to 12.6 +/- 7 after 4 weeks of treatment. Valproate blocked reinduction of panic symptoms on lactate rechallenge in 10 (83%) of 12 patients who had initially experienced panic symptoms on initial infusion. The significant reduction in spontaneous panic attacks and the blockade of lactate-induced panic symptoms by valproate support earlier studies suggesting that the drug may be an effective treatment for panic disorder. PMID- 8513041 TI - Acute tryptophan depletion in autistic disorder: a controlled case study. PMID- 8513042 TI - Measures of visual scanning as a predictor of cocaine cravings and urges. PMID- 8513043 TI - Effects of haloperidol decanoate on plasma homovanillic acid in chronic schizophrenic patients. PMID- 8513044 TI - Cortisol secretion in remitted late-life depressives. PMID- 8513045 TI - Society for the Study of Reproduction. 26th Annual Meeting. Fort Collins, Colorado, August 1-4, 1993. Abstracts. PMID- 8513046 TI - Malaria: overview and update. PMID- 8513047 TI - "AIDS-ology": an interventional specialty. AB - The AIDS Commentaries have focused primarily upon the clinical aspects of infection due to the human immunodeficiency virus as documented in academic centers based in large metropolitan areas. Clinicians outside the epicenters of the epidemic face a different set of problems. Dr. Verghese has previously shared his experience in caring for persons with AIDS in rural Tennessee (J Infect Dis 1989;160:1051-5). In this latest contribution, he discusses the potential value of training infectious diseases physicians to perform procedures that they usually do not learn in fellowship programs but that are required for optimal management of patients with AIDS. This is a controversial issue that reflects a shift in the infectious disease specialty from a consultative to a primary care practice as a result of the AIDS epidemic. It is an issue worthy of consideration by the directors of infectious disease training programs. PMID- 8513048 TI - Disseminated infection with rapidly growing mycobacteria. AB - Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon. Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years. We identified 46 other cases by review of the medical literature since 1960. We categorized these 54 cases into three groups according to underlying disease and outcome. Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%). Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness. The survival rate in this group was only 10%. Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy. These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival. PMID- 8513049 TI - Tularemia from a cat bite: case report and review of feline-associated tularemia. AB - We report the case of a 63-year-old man who developed ulceroglandular tularemia complicated by pneumonia following a cat bite. A review of the literature revealed 51 cases of cat-related tularemia reported since 1928. Details of 15 cases (including the present case) were available and analyzed. If, following feline contact, patients develop pneumonia or if patients with skin and soft tissue infection fail to respond to therapy with penicillin, physicians should be alerted to the possibility of tularemia. A greater awareness of this complication following a cat bite or cat scratch is important for recognizing this uncommon infection. PMID- 8513050 TI - Significant recovery of nonsporulating anaerobic rods from clinical specimens. AB - Eighteen isolates of Bifidobacterium species, 99 of Eubacterium species, and 38 of anaerobic Lactobacillus species were recovered from 3,971 clinical specimens submitted to the anaerobic microbiology laboratory at the National Naval Medical Center over a period of 10 years (June 1978 to June 1988). Clinically significant infection was documented in association with 53 isolates recovered from 52 patients: 8 (44%) of the 18 Bifidobacterium isolates, 30 (30%) of the 99 Eubacterium isolates, and 15 (39%) of the 38 Lactobacillus isolates. The rest of the isolates were considered to be contaminants or to be of uncertain pathogenic significance. The significant infections that were documented mostly involved abdominal abscesses, obstetric and gynecologic sites, and wounds. Predisposing conditions (primarily prior surgery, immunodeficiency, malignancy, presence of a foreign body, or diabetes) were apparent in 7 (87.5%) of the 8 patients infected with Bifidobacterium species, in 23 (85%) of the 27 patients infected with Eubacterium species for whom clinical records were available, and in 8 (67%) of the 12 patients infected with Lactobacillus species for whom clinical records were available. Antimicrobial therapy was administered to 40 (85%) of the 47 patients for whom clinical records were available; such treatment was given in conjunction with surgical drainage or correction for 31 of these 47 patients (66%). No patient died of infection due to anaerobic, nonsporulating, gram positive rods. These data illustrate that, although Bifidobacterium, Eubacterium, and Lactobacillus species are infrequently associated with infections, they occasionally do cause serious illness. PMID- 8513051 TI - Primary actinomycotic endocarditis: case report and review. AB - Endocarditis due to Actinomyces species for which a portal of entry cannot be identified is extremely rare. We present a case of primary endocarditis due to Actinomyces israelii with an unknown portal of entry and review seven similar cases reported in the literature since 1939. The disease predominantly affects males. Clinical features are similar to those of bacterial endocarditis due to other organisms. Penicillin remains the drug of choice for treatment of this condition. The optimal duration of treatment has not yet been determined; however, with early diagnosis and appropriate antimicrobial therapy, the prognosis is good. PMID- 8513052 TI - Infection of an arterial prosthesis as the presenting manifestation of disseminated coccidioidomycosis: control of disease with fluconazole. AB - We describe an elderly man whose presenting manifestation of disseminated coccidioidomycosis was bilateral infection of femoral arterial prosthetic grafts. After the patient failed to respond to both ketoconazole and amphotericin B, treatment with fluconazole brought about clinical resolution of meningitis and pulmonary disease and, in combination with repeated percutaneous aspiration, control of the arterial infection. The unusual clinical features of this case, along with the incidence and management of prosthetic arterial infections caused by fungi, are discussed. PMID- 8513053 TI - Q fever meningoencephalitis in a soldier returning from the Persian Gulf War. AB - Acute infection with Coxiella burnetti usually results in a self-limited illness requiring a high index of clinical suspicion for diagnosis. Although headache is a common presentation of acute infection with this agent, focal neurological deficits are considered to be limited to chronic infection, most commonly caused by emboli from endocarditis. We report the case of a soldier returning from Desert Storm who presented with headache and a crescendo pattern of transient ischemic attacks and had serology consistent with an acute Q fever infection. The English-language literature on central nervous system infection caused by Coxiella burnetti is reviewed. PMID- 8513054 TI - Fatal noncutaneous visceral infection with varicella-zoster virus in a patient with lymphoma after autologous bone marrow transplantation. AB - After undergoing high-dose chemotherapy and autologous bone marrow transplantation, a patient developed fatal disseminated infection due to varicella-zoster virus (VZV) with no coincident skin lesions. This article describes this unusual case and briefly reviews the English-language literature on the abdominal presentation of VZV infection as well as that on VZV infection after bone marrow transplantation. In the severely immunocompromised host, visceral infection with VZV may uncommonly occur in the absence of skin lesions. The possibility of such infection should be considered when immunocompromised patients develop unusual symptoms or other evidence of visceral disease (e.g., cholecystitis). PMID- 8513055 TI - Trichinosis with ventilatory failure and persistent myocarditis. AB - Life-threatening infections with Trichinella spiralis are rare in countries that have adopted laws requiring cooking of raw garbage fed to pigs. Thus such infections may pose a diagnostic dilemma for clinicians unfamiliar with their presentation. We report a case of imported trichinosis in a Mexican national who developed respiratory failure, myocarditis, and sinus arrest. The patient recovered uneventfully after the administration of benzimidazole and corticosteroid drugs, although a pacemaker was required to maintain normal cardiac rhythm. Symptomatic myocarditis is a rare complication of trichinosis that is often associated with increased morbidity and mortality. This report illustrates and reviews important features of the epidemiology, clinical presentation, and management of trichinosis. PMID- 8513057 TI - Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States. AB - AIDS surveillance data reported to the Centers for Disease Control from January 1981 through December 1991 were analyzed in a study characterizing persons with human immunodeficiency virus (HIV) infection and extrapulmonary tuberculosis (EPTB) in the United States. Among 206,392 persons reported to have AIDS, 4,751 (2.3%) were also reported to have EPTB; of these cases, 4,257 (90%) were reported after September 1987, when the case definition for AIDS was revised to include EPTB. Seventy-six percent of persons in whom AIDS and EPTB were reported after this revision were born in the United States; among these persons, the annual percentage with EPTB in 1988-1991 ranged from 2.3% to 2.5%. The South and the Northeast accounted for 73% of EPTB cases in U.S.-born persons. U.S.-born non Hispanic blacks (odds ratio [OR], 3.3) and U.S.-born Hispanics (OR, 2.1) were more likely than U.S.-born non-Hispanic whites to be reported as having EPTB. Intravenous drug users were at higher risk (OR, 2.9) than men who reported having had sex with other men. With the resurgence of tuberculosis and the continued expansion of the HIV epidemic, these data provide a useful basis for the targeting of efforts to control tuberculosis and to prevent HIV infection. PMID- 8513056 TI - Nocardiosis in renal transplant recipients undergoing immunosuppression with cyclosporine. AB - Nine cases of nocardiosis were diagnosed among 1,255 renal transplant recipients given cyclosporine (CsA)-prednisone for immunosuppression between August 1980 and March 1992 (incidence, 0.7%). Of these nine patients presenting with nocardiosis 32-1,806 days after transplantation, eight had pulmonary involvement, two had skin manifestations (one with localized disease), and one had a cerebral abscess and a pleural effusion. All cases required aggressive diagnostic procedures. Nocardia asteroides was isolated in seven cases and Nocardia brasiliensis in two. All but one case was cured. Included among the cures were all of four cases treated with amoxicillin/clavulanic acid. Therapy with CsA-prednisone was continued throughout the infection in eight cases. Analysis of a group of 154 historical controls who received azathioprine (AZA)-prednisone for immunosuppression after renal transplantation (performed before 1980 at the same center) revealed four cases of nocardiosis (incidence, 2.6%). Thus nocardiosis is apparently less common among renal transplant recipients given CsA-prednisone than among those given AZA-prednisone. The clinical presentation of nocardiosis in renal transplant recipients is variable, with pulmonary involvement predominating. Diagnosis requires an aggressive approach. Chemotherapy is successful in most cases, including those treated with amoxicillin/clavulanic acid when the isolate is susceptible. PMID- 8513058 TI - Predictive value of bronchoalveolar lavage in excluding a diagnosis of Pneumocystis carinii pneumonia during prophylaxis with aerosolized pentamidine. AB - We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine. PMID- 8513059 TI - Variation in phenotypic expression of the Opa outer membrane protein and lipooligosaccharide of Neisseria meningitidis serogroup C causing periorbital cellulitis and bacteremia. AB - Expression of the Opa outer membrane protein varies widely among isolates of Neisseria meningitidis; the clinical significance of this variation is unclear. A sialic-acid acceptor is present in the lipooligosaccharide of some strains of Neisseria and has been shown to render Neisseria gonorrhoeae serum-resistant. We report the case of a patient who had an unusual clinical manifestation of infection due to N. meningitidis serogroup C, periorbital cellulitis with concomitant bacteremia. Clinical isolates from the blood and aspirate of the periorbital cellulitis were identical except for the phenotypic expression of the Opa outer membrane protein in the isolate from the periorbital cellulitis and in the lipooligosaccharide phenotype of the sialic-acid acceptor as defined by monoclonal antibodies. We discuss the laboratory and clinical implications of these findings. PMID- 8513060 TI - Concomitant amphotericin B therapy, granulocyte transfusions, and GM-CSF administration for disseminated infection with Fusarium in a granulocytopenic patient. AB - The use of granulocyte transfusions during amphotericin B treatment of invasive fungal infections in granulocytopenic patients is controversial because of concern about pulmonary complications from leukostasis. Moreover, the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with active infections has been questioned because of reports that this cytokine inhibits neutrophil migration into areas of inflammation. We report a case in which the combined use of amphotericin B, granulocyte transfusions, and GM-CSF was safe and life-saving in a pancytopenic patient with disseminated fusarium infection. Histologic evidence of the migration of neutrophils into an area of active infection was found. PMID- 8513061 TI - Soft-tissue infection due to Mycobacterium smegmatis: report of two cases. AB - Mycobacterium smegmatis is an uncommon pathogen in humans. Fourteen cases of skin or soft-tissue infection due to M. smegmatis have been previously reported. We report two cases of posttraumatic M. smegmatis infection of the lower extremity. M. smegmatis infection produces chronic cellulitis with fistula formation that is most commonly a result of direct traumatic inoculation of contaminated material. Extensive surgical debridement followed by skin grafting has been necessary for cure in the majority of cases. PMID- 8513062 TI - Measurement of levels of tumor necrosis factor-alpha and interleukin-1 beta in the CSF of patients with meningitis of different etiologies: utility in the differential diagnosis. AB - We assayed tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations in CSF from patients with meningitis of different etiologies and tested the usefulness of these assays for differentiating between pyogenic meningitis and aseptic meningitis of different etiologies. We used a monoclonal antibody ELISA to test 125 CSF specimens from patients whose cases were classified as follows: pyogenic meningitis (n = 20), viral meningitis (n = 22), self-resolving aseptic meningitis for which no specific diagnosis was made (n = 25), meningitis due to other infectious agents (n = 11), and neoplastic meningitis (n = 5); we also tested normal CSF from healthy patients (n = 20) and those with neurological diseases (n = 22). Levels of TNF-alpha were above 200 pg/mL in 16 of 20 patients with pyogenic meningitis, but not in patients in the other groups. Levels of IL-1 beta were above 100 pg/mL in 15 of 20 patients with pyogenic meningitis and in one patient with a brain abscess. A positive correlation between levels of these cytokines and different inflammatory parameters was noted, whereas an inverse relationship with the duration of symptoms was observed. With regard to diagnosis, measurement of TNF-alpha and IL 1 beta levels showed sensitivities of 84.2% and 78.9%, respectively; specificities of 100% and 99%, respectively; a positive predictive value of 1 and 0.93, respectively; and a negative predictive value of 0.97 and 0.96, respectively. PMID- 8513063 TI - Persistent fever due to occult dental infection: case report and review. AB - Dental sepsis is one potential cause of persistent fever that can escape detection. A patient with febrile episodes due to an occult tooth abscess of 2 years' duration is described. A search of the English-language literature revealed 20 other cases of fever of obscure origin arising from dental sources. This diagnosis may be suggested by repeated questioning of the patient about his or her medical history, repeated physical examination, an elevated erythrocyte sedimentation rate, or a history of failure to respond to antibiotic therapy. Dental infection is unlikely in patients who have a white blood cell count of > 11 x 10(9)/L, a temperature of > 39.5 degrees C, or positive blood cultures. The diagnosis may be made by repeated focused clinical examination, dental roentgenography, or radiolabeled leukocyte scintigraphy. Detection of dental sepsis is worthwhile since the febrile condition can be cured in all instances by tooth extraction and abscess drainage, with or without concurrent antibiotic therapy. PMID- 8513064 TI - A cutaneous lesion in a patient with AIDS: an unusual presentation of infection due to Mycobacterium avium complex. AB - A patient with AIDS developed a purplish, necrotic skin lesion followed by fevers, constitutional symptoms, and watery diarrhea. Stains of samples from the skin lesion and of stool and bone marrow revealed acid-fast bacilli, and Mycobacterium avium was isolated from cultures of these specimens and blood. With the initiation of multiagent oral antimycobacterial therapy, the patient's symptoms abated and the cutaneous lesion reepithelialized. We believe this lesion to be a manifestation of disseminated infection due to Mycobacterium avium complex (MAC). As the population of patients with AIDS who have CD4 cell counts of < 100/mm3 increases, new and unusual manifestations of disseminated MAC infection can be expected. New oral agents with increased activity against MAC may make early recognition and treatment of MAC infections more rewarding. PMID- 8513065 TI - Experience at a referral center for patients with suspected Lyme disease in an area of nonendemicity: first 65 patients. AB - A multidisciplinary referral center was established at a university hospital for prospectively assessing patients with possible Lyme disease. Borrelia burgdorferi is not known to be endemic in this region, but considerable anxiety about Lyme disease has developed among the general public. Sixty-five patients were referred for suspected Lyme borreliosis. Detailed histories were obtained and physical examinations were performed; patients were investigated aggressively in accordance with their symptom complexes. Strict diagnostic criteria consistent with published standards were applied. Only two of the 65 patients were judged to have probable Lyme disease. Definite major alternate diagnoses were made for 50 patients (77%); firm medical diagnoses (11 dermatologic, 9 rheumatologic, 9 infectious disease, 6 gastrointestinal, 4 neurological, and 2 miscellaneous) were made for 41 patients (63%); and major psychiatric diagnoses were made for 9 patients (14%). Probable diagnoses of chronic fatigue syndrome and fibromyalgia were made for 11 patients (17%). The conditions of four patients (6%) were undiagnosed. A referral center for patients with suspected Lyme disease can be useful even in an area of nonendemicity, and careful clinical assessment will reveal treatable alternate diagnoses for many patients with suspected Lyme disease. PMID- 8513066 TI - Antimicrobial susceptibility patterns and resistance transferability among Bacteroides fragilis group isolates from patients with appendicitis in Bali, Indonesia. AB - Patterns of antimicrobial susceptibility were determined for 155 clinical isolates of the Bacteroides fragilis group from patients with acute appendicitis in Bali, Indonesia. The transfer of drug resistance was also studied, and plasmid analyses were undertaken. Metronidazole and chloramphenicol were the most active drugs against these isolates (resistance rate, < or = 0.6%). Among the beta lactam drugs, cefoxitin was the most active (resistance rate, 2%). Rates of resistance to tetracycline were high (16%). Resistance to clindamycin (rate, 10%) increased during the 2-year study period. Except in the case of beta-lactam agents, overall susceptibility patterns were comparable to those reported from other countries. Tetracycline resistance was more frequently transferred after tetracycline induction than without such induction (P < .05, chi 2 test). Resistance to tetracycline and clindamycin was co-transferred by five of 12 donor strains. In one of these five strains, transferability was constitutive, with a high transfer frequency (10(-5) per input donor). Plasmid analysis indicated that the transfer of resistance to tetracycline and clindamycin among the strains studied was not plasmid mediated. PMID- 8513067 TI - Course and outcome of bacteremia due to Staphylococcus aureus: evaluation of different clinical case definitions. AB - In a retrospective survey of patients hospitalized in the University Hospital of Basel, Switzerland, the course and outcome of 281 cases of true bacteremia due to Staphylococcus aureus over a 7-year period were analyzed. The main purpose was to evaluate different case definitions. In 78% of cases the source of bacteremia was obvious; vascular access sites (27%) and wounds (10%) were the most common sources. Metastasizing foci were more common in cases of primary vs. secondary bacteremia (P < .001). The incidence of endocarditis was higher in cases in which no portal of entry was defined (P < .03). The overall mortality rate was high at 34% partly because of inappropriate initial antibiotic therapy. With the introduction of an infectious disease service at the hospital, the fraction of misjudged results of blood culture diminished 2.5-fold. Among the differently defined cases, the mortality rate was significantly higher for cases of complicated vs. uncomplicated bacteremia (P < .01), for cases of primary vs. secondary bacteremia (P = .05), and for patients with endocarditis or other secondary foci (P < .001). Since only one methicillin-resistant strain was isolated, multiresistant staphylococci were not a problem in the hospital. Different case definitions allowed the detection of patients at increased risk for complications and death. In the treatment of sepsis with no evident focus, initial antimicrobial therapy should include the use of agents with antistaphylococcal activity. PMID- 8513068 TI - Spectrum of extraintestinal disease due to Aeromonas species in tropical Queensland, Australia. AB - During a 12-month period, the clinical spectrum of extraintestinal disease due to Aeromonas species was determined for 56 patients in tropical Queensland (Australia). Forty-six patients acquired their infection in the community, six patients were infected in the hospital, and four patients were colonized. Demographic risk factors included male gender (67%) and Aboriginal ethnic background (35%). The disease ranged from deep-seated infection (four cases) to soft-tissue infection of varying intensity (48 cases). Among patients whose infections were community acquired, 22 required hospitalization and 27 suffered trauma-associated infection. Seventeen patients (63%) in the latter group had lacerations to the hands and feet that were contaminated with surface water or soil. The appearance of the wounds was not pathognomonic, and diagnosis was made by laboratory evaluation. Aeromonas was the sole pathogen in nine patients. Polymicrobial infections were due to Aeromonas and mainly Staphylococcus aureus and/or mixed enteric bacteria. Aeromonas hydrophila was the most common species isolated (71%), followed by Aeromonas sobria (25%). In nine cases, the empirical antibiotic regimen prescribed did not adequately cover infection due to Aeromonas. Infection was seen regularly throughout the year, but a cluster of cases also occurred during the tropical Australian wet season. PMID- 8513069 TI - Infectious diseases during the Civil War: the triumph of the "Third Army". AB - The American Civil War represents a landmark in military and medical history as the last large-scale conflict fought without knowledge of the germ theory of disease. Unsound hygiene, dietary deficiencies, and battle wounds set the stage for epidemic infection, while inadequate information about disease causation greatly hampered disease prevention, diagnosis, and treatment. Pneumonia, typhoid, diarrhea/dysentery, and malaria were the predominant illnesses. Altogether, two-thirds of the approximately 660,000 deaths of soldiers were caused by uncontrolled infectious diseases, and epidemics played a major role in halting several major campaigns. These delays, coming at a crucial point early in the war, prolonged the fighting by as much as 2 years. PMID- 8513070 TI - Gemella haemolysans endocarditis. PMID- 8513071 TI - Hypothermia as a presenting sign of brucellosis. PMID- 8513072 TI - Meningitis simultaneously due to Cryptococcus neoformans and Mycobacterium tuberculosis. PMID- 8513073 TI - Staphylococcus schleiferi: a new opportunistic pathogen. PMID- 8513074 TI - Severity of tetanus in patients older than 80 years: comparative study with younger patients. PMID- 8513075 TI - A review of the Japanese Pharmaceutical Manufacturers' Association database currently established to examine retrospectively the value of long-term animal toxicity studies. PMID- 8513076 TI - How useful are chronic (life-span) toxicology studies in rodents in identifying pharmaceuticals that pose a carcinogenic risk to humans? AB - After 20 years' experience of the chronic rodent bioassay and in the light of our current understanding of the mechanisms of carcinogenesis, there is now a wide recognition that the present strategies for assessing carcinogenic risk of pharmaceuticals are in need of urgent revision. The few pharmaceuticals known to cause cancer in humans each possess at least one of four properties: genotoxicity, immunosuppression, hormonal activity or chronic irritation. These properties can be identified by genotoxicity studies in vivo and well-designed toxicology studies of up to 6 months duration in rats. About 50% of all chemicals evaluated in the bioassay are positive. The findings from non-genotoxic compounds can often be shown to lack relevance for humans because either the exposure (daily dose and duration) is excessive when compared with actual human exposure or the response to a carcinogenic challenge is qualitatively different in rodents from that in humans. Many studies of the mechanisms of carcinogenesis in rats have elucidated why the data generated in rat bioassays are often not relevant to humans. However, the relative paucity of pharmacological data in mice means that similar studies of mechanism cannot be carried out so effectively in mice. The results of mouse bioassays are dominated by the frequency with which the liver (and, to a lesser extent, the lung) is a target organ. Molecular biology is now providing evidence of why chemically induced tumours in this organ cannot be extrapolated to human risk. Examination of the pattern of results in the NTP and IARC bioassay databases and the rodent data for 18 chemicals which appear thus far not to be carcinogenic in humans, indicates that data generated in mouse bioassays do not contribute to human carcinogenic risk assessment. It is argued that, for pharmaceuticals, only compounds with a novel mode of action need be studied for longer than 6 months. For such compounds, a study in rats at pharmacodynamically relevant dose levels for 12-18 months will, in general, provide adequate information for carcinogenic risk assessment in humans. PMID- 8513077 TI - The value of the dog in long-term toxicity studies. The CMR international toxicology database. PMID- 8513078 TI - A retrospective comparison of the results of 6 and 12 month non-rodent toxicity studies. PMID- 8513079 TI - [Hypercholesterolemia. Are we aware of the magnitude of the problem?]. PMID- 8513080 TI - [Comparative study of the lipid profiles in the health staff versus the non health staff at a health center]. AB - Levels of cholesterol (CT) and lipoproteins fractions (c-LDL and c-HDL), as well as the atherogenic index (CT/c-HDL), were assessed in 307 workers of a health center. The study population was classified into groups, based on age and sex and whether they were health (physicians, registered nurses, clinical assistants) or non-health staff. The lipidic profile of the health staff groups was similar to the profile of non-health staff groups of the same age and sex. The percentage of subjects with CT above 200 mg/dl. was significantly higher (79.6 vs 60.9%) (p < 0.05) among the male health staff versus the male non-health staff and lower among the female health staff versus the female non-health staff (34.5 vs 55.5%) (p < 0.05). The differences in the lipidic profile depending on age and sex were confirmed grouping the population on the basis of such criteria. We highlight that all groups, with the exception of the female health staff, had CT levels above those recommended by the WHO and we stress the need of making health professionals aware of the importance of a primary prevention plan for the control of the cholesterolemia. PMID- 8513081 TI - [Effects of dietary oil (olive/sunflower) on the plasmatic apolipoprotein profile]. AB - FOUNDATIONS: The dietary oil provides a significant portion of the caloric intake in the form of fat, although there is some controversy with respect to the potential positive action of each type of oil. In this study, the effect on the lipo-apoprotein profile of monounsaturated fatty acids (MUFA) provided by olive oil and the polyunsaturated fatty acids (PUFA) provided by girasol oil are compared in a population with high risk of arteriosclerosis, as it is the aged population. METHODOLOGY: 44 aged patients living in the same institution, 21 males and 23 females (age: 79 +/- 6 years), and following two different diets during 3 months, with olive and girasol oils, respectively, participated in the study. Both diets were isocaloric: 2.300 kcal/day, 17% proteins, 33% lipids (30 g/day of oil), and 50% carbohydrates. Plasmatic concentrations of cholesterol (C), triglycerides (TG), c-LDL, c-VLDL, c-HDL2, c-HDL3 and lipoprotein a (Lp[a]), as well as apoproteins A1, B, CII, CIII and E, were assessed. Applied statistics: Student's t test for matched samples. RESULTS: C and TG plasmatic levels did not changed, whereas levels of c-LDL decreased significantly, as well as levels of polyunsaturated fatty acids (135 +/- 43 and 124 +/- 33 mg/dl., p < 0.009) and levels of apo B (151 +/- 47 and 139 +/- 36 mg/dl., p < 0.009). Levels of c-HDL increased significantly (49 +/- 14 and 52 +/- 16 mg/dl., p < 0.01) as well as levels of apo A1 (190 +/- 32 and 205 +/- 41 mg/dl., p < 0.01). Levels of apo CIII (8.2 +/- 2.8 and 9.9 +/- 3.2 mg/dl., p < 0.008) and apo E (3.2 +/- 1.1 and 3.7 +/ 0.9 mg/dl., p < 0.01) also increased in men. Women did not showed any significant variations in lipoproteins, although apo A1 and apo E increased slightly and apo B decreased, although not significantly, with the polyunsaturated fat. The levels of Lp(a) did not changed. CONCLUSIONS: In the aged population following a standard diet, without overloads, the PUFAs induced positive changes in the lipoapoprotein profile when compared to a previous diet with MUFA. Those changes were more evident in men than in women. PMID- 8513082 TI - [Diffuse pulmonary hemorrhage: review of nine cases]. AB - Nine cases of diffuse pulmonary hemorrhage (DPH) diagnosed in our hospital during the past eight years are reviewed. We assess the clinical, diagnostic, etiologic and evolutive characteristics of all these cases and, thus, of such entity in our environment. The nine patients had anemia, hemoptysis and transient pulmonary infiltrations. Renal affectation was observed in seven patients. Based on clinical and laboratory data, supplementary explorations and immunological and histological studies, the following etiologic diagnosis were established: idiopathic extracapillary glomerulonephritis (three cases), idiopathic pulmonary hemosiderosis (two cases), Wegener's granulomatosis (one case), unclassifiable systemic necrosant vasculitis or overlapping syndrome (two cases). In one patient, it was not possible to establish the etiology. Global mortality was 44.4% (four patients); two of them died during the course of the initial massive hemoptysis (not controlled, as in the other patients, with steroids) and two other patients died due to late complications. In this series, none of the patients developed a disease associated to antibodies against the basal membrane. The application of a severe diagnostic systematic has been a key factor for the management of these patients. PMID- 8513083 TI - [Evaluation of metabolic control in a summer camp for diabetic children (Villarcayo 1991)]. AB - The relevance of the diabetological education in the treatment of diabetis mellitus must be a prioritary goal in order to reach a proper metabolic control and to avoid as much as possible both acute metabolic complications and long-term vascular and neurological complications, achieving thus a total integration of the diabetic patient in the society. We have monitored during 15 days a group of diabetic children with IDDM in a summer camp, assessing in all of them several clinical and biochemical parameters. The results have been statistically analyzed using the Student's test. After the stay in the summer camp, we observed a significant reduction in the total dose of insulin (p < 0.001) and in the number of hypoglycemias (p < 0.001) and an increase in the average levels of capillary glycemia at the end of the study period when compared with the beginning, with p < 0.001 (breakfast preprandial), p < 0.05 (lunch preprandial) and p < 0.01 (dinner and night preprandial). We did not observe any significant differences in the other parameters studied. In inclusion, the stay in the summer camp of this group had a positive effect, achieving a better metabolic control with lower doses of insulin. PMID- 8513084 TI - [Breast cancer in men. Clinical study of four cases in a department of internal medicine]. AB - Breast neoplasias among men are rare, its incidence being 1% of all breast cancers in both sexes. We present four cases of breast cancer in men, given their low frequency and rare manifestations. We describe the clinical manifestations, stressing that health education for its detection must be extended to men. We comment as well on the value of hormonal receptor assessment for the prediction of a hormonal treatment in advanced breast cancers. PMID- 8513085 TI - [Sclerodermia and nephro-urological tumors. Presentation of two cases]. AB - The association between sclerodermia and malignant diseases is estimated around 3 7%. We present two cases of this disease concomitant to nephro-urological tumors. In one of these cases, we detected a hypernephroma in a patient with signs of florid sclerodermia, which did not disappear after nephrectomy and later showing evidence of metastasis. The other patient showed sclerodermiform signs developing quickly after transurethral resection of a vesical carcinoma. The highest incidence of associated neoplasias is observed in lung and breast cancers, hematological carcinoids and melanomas. Nephro-urological tumors are present in 0.3-0.5%. PMID- 8513086 TI - [Mycobacteriosis from Mycobacterium szulgai in a patient with human immunodeficiency virus infection]. AB - We present a case of renal and, probably, bone mycobacteriosis by M. szulgai in a patient infected by the human immunodeficiency virus (HIV). M. szulgai is an atypical skotochromogen mycobacterium rarely described in the literature. Clinically, it is characterized by the predominance of pulmonary manifestations undistinguishables from M. tuberculosis, and rarely affecting other organs. In our environment, such mycobacterium has never been isolated in the main series published in the literature. The evolution of the patient was good, disappearing the clinical signs after the tuberculostatic treatment. The antibiogram showed resistance to rifampicine, piracinamide and ethambutol. PMID- 8513087 TI - [Pleural empyema as a complication of the sclerotherapy of esophageal varices]. AB - We present three patients developing pleural empyema after sclerotherapy of esophagic varixes. In all of them, the presence of persistent fever syndrome following the sclerotherapy, along with radiological images of pleural overflow, were the starting point of the patient's study. In the emergency esophagogrames, the extravasation of contrast outside the esophagus could not be confirmed. The treatment, which must be started as soon as possible, was based in conservative measures (drainage, antibiotics and a proper nutrition), given the poor general condition of these patients. Despite all these measures, the prognosis is poor, with two of the three patients dying despite the administration of the treatment. In conclusion, although its frequency is very low, pleural empiema is an extremely severe complication of the sclerotherapy of esophagic varixes. If this complication is suspected, the prognosis depends on a treatment that must be started as soon as possible. PMID- 8513088 TI - [Prevention of tuberculosis infection]. AB - Tuberculosis (TB) is a disease caused by a mycobacterium, whose incidence has increased in the past years. This increase is related to the adquired immunodeficiency syndrome (AIDS). Due to its high prevalence, Spain is considered a developing country. The tuberculous infection depends on the degree of functionality of the alveolar macrophages that stimulate the lymphocytes and isolate the bacillus. The infection by mycobacterias can be quantified by means of the cutaneous reaction against tuberculin and mantoux, allowing us to select the subjects that must receive prophylaxis. For its correct interpretation, it is currently recommended to avoid BCG vaccination of children, except in countries with high prevalence of TB. PMID- 8513089 TI - [Literature review on fenofibrate]. AB - Phenofibrate is one of the hypolipidemic agents derived from the fibric acid that is more frequently used nowadays, because it has shown several advantages over other hypolipidemics belonging to the same family, and a greater power, which allows to obtain greater reductions in LDL levels and less side effects. Its mechanism of action affects basically the metabolism of triglycerides, with a reduction in their synthesis and an increase in their catabolism, being able to act as well on the metabolism of cholesterol, mainly at the level of its catabolism. The phenofibrate, thus, has apparently shown a significant hypolipidemic effectivity, decreasing plasmatic levels of c-LDL and triglycerides and increasing levels of c-HDL, resulting in a less atherogenic lipidic profile. PMID- 8513090 TI - [Amylin: its potential role in the etiopathogenicity of diabetes mellitus]. AB - The recent discovery that IAPP, or amylin, a polypeptide solubilized from the amyloid substance found in the islets of Langerhans of most type II diabetics, is secreted along with insulin by beta cells and possesses anti-insulinic effects has opened new perspectives in the etiopathogenesis of this type of diabetes. Many data suggest a possible hormonal mechanism acting on perypheral targets, though so far effects have only been observed with supraphysiological doses. Other reports suggest amylin would have a deleterious effect on beta cells, because of its deposition in the form islet amyloid. PMID- 8513091 TI - [Disease caused by iron overload associated to minor beta thalassemia]. PMID- 8513092 TI - [A new case of mediterranean boutonneuse fever developing multiple complications]. PMID- 8513093 TI - [Pleural effusions, a rare manifestation of infection from Pneumocystis carinii]. PMID- 8513094 TI - [Hydrochlorothiazide and non-cardiogenic pulmonary acute edema: presentation of a new case]. PMID- 8513095 TI - Statistical models for prevalent cohort data. AB - In prospective cohort studies individuals are sometimes recruited according to a certain cross-sectional sampling criterion. A prevalent cohort is defined as a group of individuals who have a certain disease at enrollment into the study. Statistical models for the analysis of prevalent cohort data are considered when the onset or diagnosis time of the disease is known. The incident proportional hazards model, where the time scale is duration with disease, is compared to the prevalent proportional hazards model, where the fundamental time scale is follow up time. In certain cases the time of enrollment may coincide with another event (such as the initiation of treatment). This situation is also considered and its limitations highlighted. To illustrate the methodological ideas discussed in the paper, the analysis of data from an observational study of zidovudine (ZVD) in patients with the acquired immunodeficiency syndrome (AIDS) is presented. PMID- 8513096 TI - Modelling overdispersion in toxicological mortality data grouped over time. AB - Toxicologists frequently conduct toxicity experiments in which different treatment conditions are applied to groups of animals and the resulting mortality in each group is measured at a number of discrete time points over the course of the experiment. Both survival analysis and generalized linear models have been proposed for analyzing this type of data. Whatever the approach taken, the model should allow for the presence of extra-multinomial variation arising from the use of groups of animals rather than individuals as the experimental units. We consider a number of models for overdispersion that can be incorporated into the generalized linear model framework for multinomial data. These models are extensions of ones proposed for binomial data by Williams (1982, Applied Statistics 31, 144-148) and Moore (1986, Biometrika 73, 583-588; 1987, Applied Statistics 36, 8-14). In addition, we examine robust asymptotic covariance matrix estimators for regression parameters, similar to those given in Liang and Zeger (1986, Biometrika 73, 13-22) and Zeger and Liang (1986, Biometrics 42, 121-130), and compare them to the model-based asymptotic estimators. Recommendations for analysis are given. PMID- 8513097 TI - Test for interaction between treatment and stratum with ordinal responses. AB - A measure of interaction between treatments and stratum is proposed when there are two treatments and the response variable is measured on an ordered categorical scale. A test of the hypothesis of no interaction and a test of the hypothesis of no treatment effect are given and approximate expressions for the powers of these tests are obtained. Monte Carlo simulation is performed to examine the Type I error rate and the accuracy of the approximate power formulae of the tests. The loss of power of the tests due to combining categories is also examined. The simulation study shows that our methods perform well even in samples of size 20, and that the dichotomization results in appreciable loss of power. PMID- 8513098 TI - Analyzing doubly censored data with covariates, with application to AIDS. AB - This paper proposes a method for incorporating covariate information in the analysis of survival data when both the time of the originating event and the failure event can be right- or interval-censored. This method generalizes the one sample estimation results of De Gruttola and Lagakos (1989, Biometrics 45, 1-11) by allowing the distribution of time between the two events to be a function of covariates under a proportional hazards model. Estimates for the model coefficients, as well as the underlying distributions, are obtained by an iterative fitting procedure based on Turnbull's (1976, Journal of the Royal Statistical Society, Series B 38, 290-295) self-consistency algorithm in combination with the Newton-Raphson algorithm. The method is illustrated with data from a study of hemophiliacs infected with the human immunodeficiency virus. PMID- 8513099 TI - Quasi-symmetric latent class models, with application to rater agreement. AB - Suppose we observe responses on several categorical variables having the same scale. We consider latent class models for the joint classification that satisfy quasi-symmetry. The models apply when subject-specific response distributions are such that (i) for a given subject, responses on different variables are independent, and (ii) odds ratios comparing marginal distributions of the variables are identical for each subject. These assumptions are often reasonable in modeling multirater agreement, when a sample of subjects is rated independently by different observers. In this application, the model parameters describe two components of agreement--strength of association between classifications by pairs of observers and degree of heterogeneity among the observers' marginal distributions. We illustrate the models by analyzing a data set in which seven pathologists classified 118 subjects in terms of presence or absence of carcinoma, yielding seven categorical classifications with the same binary scale. A good-fitting model has a latent classification that differentiates between subjects on whom there is agreement and subjects on whom there is disagreement. PMID- 8513100 TI - Statistical testing of genetic linkage under heterogeneity. AB - Recent advances in human genetics have led to a renewed interest in statistical methods for the detection of linkage from family data--for example, between marker loci and disease traits. Statistical analysis of linkage between two loci is carried out almost exclusively by means of the lod (log-odds) score test, equivalent to a likelihood ratio test. The current practice is to declare genetic linkage between loci when the maximum lod score exceeds 3. As will be discussed here, the lod-score approach is not appropriate for the detection of linkage from heterogeneous data, e.g., when families consist of a mixture of linked and unlinked types. Heterogeneity may arise, for example, when rare mutations at different genetic loci are responsible for the same disease trait. As an alternative approach to account for possible heterogeneity in the detection of linkage, we propose the application of large-sample test statistics that are members of Neyman's class of C(alpha), or partial score tests. The convergence of the proposed test statistics to their asymptotic distributions is investigated via Monte Carlo simulation for typical study designs applicable in human genetics. PMID- 8513101 TI - On the irreducibility of a Markov chain defined on a space of genotype configurations by a sampling scheme. AB - Techniques from image processing are now being considered for use in pedigree analysis. Although the method that we develop here was motivated by considering it as an analogue to the Gibbs sampler, we justify it independently using the ergodic theorem for aperiodic, irreducible, finite Markov chains. While it is trivial to show that aperiodicity holds, irreducibility is a more interesting condition. Proofs of irreducibility are provided for some special cases and counterexamples are provided for others. Where irreducibility does not hold, an alternative method using relaxed genetic parameters and rejection is recommended and justified. PMID- 8513102 TI - A plant-capture method for estimating the size of a population from a single sample. AB - To estimate the size of a population a plant-capture method, an alternative to the classic capture-mark-recapture model, is presented. Known or marked individuals otherwise indistinguishable from the remainder of the population are planted followed by an effort to capture members from the augmented population. Maximum likelihood estimators and a confidence region together with the expected length of the confidence interval for the size of the population as a function of the number of plants are given. A methodology for comparing the cost efficiency of plant-capture to capture-recapture is developed. An application to counting the homeless is given. PMID- 8513103 TI - REML estimation for survival models with frailty. AB - A method of estimation for generalised mixed models is applied to the estimation of regression parameters in proportional hazards models for failure times when there are repeated observations of failure on each subject. The subject effect is incorporated into the model as a random frailty term. Best linear unbiased predictors are used as an initial step in the computation of maximum likelihood and residual maximum likelihood estimates. PMID- 8513104 TI - On the design and analysis of randomized clinical trials with multiple endpoints. AB - This paper considers some methods for reducing the number of significance tests undertaken when analyzing and reporting results of clinical trials. Emphasis is placed on designing and analyzing clinical trials to examine a composite hypothesis concerning multiple endpoints and combining this multiple endpoint methodology with group sequential methodology. Four methods for composite hypotheses are considered: an ordinary least squares and a generalized least squares approach both due to O'Brien (1984, Biometrics 40, 1079-1087), a new modification of these, and an approximate likelihood ratio test, due to Tang, Gnecco, and Geller (1989, Biometrika 76, 577-583). These are extended for group sequential use. In particular, simulation is used to generate critical values and sequences of nominal significance levels for the approximate likelihood ratio test, which is not normally distributed. An example is given and the relative merits of the suggested approaches are discussed. PMID- 8513105 TI - A gamma model for extra-binomial variation in dilution assays. AB - Dilution assays are widely used to estimate the concentration of a particular type of cell, called a limiting cell, in a population of cells from an animal. For each animal, the response vector is a set of binomial variables derived at different plating frequencies. Often extra-binomial variation is found when dilution assay data are analysed. This paper proposes a mixture model where the animal level effects are assumed to have a gamma distribution. This leads to more realistic standard errors for the estimates of the limiting cell concentrations. PMID- 8513106 TI - A structured compartmental model for drug kinetics. AB - A compartmental model with a structure that describes drug kinetics by incorporating the ideas of diffusion and gamma distributed clearance times is proposed. The equations describing this model may be solved by elementary numerical techniques, and the model is shown to fit a data set describing renal gentamicin concentrations, better than a simple power-function model. PMID- 8513107 TI - Constrained randomization in a therapeutic efficacy trial. AB - The use of valid constrained randomization is presented for a therapeutic efficacy trial. The construction and evaluation of randomization schemes are studied for two treatment replicates per block and for hypothesized linear gradients. Two different isomorphism classes of designs are compared using the variance of the mean squared error criterion. The results indicate that valid constrained randomization schemes can be constructed that are superior to ordinary randomization. A mastitis efficacy trial provided the specific problem to be solved. PMID- 8513108 TI - Statistical analysis of animal cancer chemoprevention experiments. AB - We explore the use of a statistical model proposed by Kokoska (1987, Biometrics 43, 525-534) for the analysis of animal cancer chemoprevention experiments. We show, using an example, that the results derived from the method can be sensitive to the parametric forms of the distributions that are assumed, particularly to the distribution of the number of tumors per animal. We propose goodness-of-fit tests to aid in the choice of the distributions. PMID- 8513109 TI - Analysis of embryonic development with a model for under- or overdispersion relative to binomial variation. AB - Observations from a study of the development of ovulations into embryos for Texel sheep are analysed with a model for count data that are under- or overdispersed relative to binomial variation. The analysis is based on maximum quasi-likelihood (McCullagh and Nelder, 1989, Generalized Linear Models, 2nd edition, London: Chapman and Hall), following an approach suggested by Williams (1982, Applied Statistics 31, 144-148). The dispersion parameter is developed as a combination of a variance component representing shared maternal effects and a correlation, typically negative, between ovulations within ewes. The number of ovulations (the binomial denominator) is included as an explanatory variable. PMID- 8513110 TI - Sequential equivalence testing and repeated confidence intervals, with applications to normal and binary responses. AB - We propose group sequential tests of the equivalence of two treatments based on ideas related to repeated confidence intervals. These tests adapt readily to unpredictable group sizes, to the possibility of continuing even though a boundary has been crossed, and to nonnormal observations. In comparing two binomial distributions, the required sample size depends strongly on the average success probability and an adaptive choice of group size is needed to produce an efficient test meeting specified error probability constraints. A special case is the experiment where interim analyses are performed, not for the purpose of early termination but simply to adjust the sample size so that nominal error rates will be guaranteed, despite the presence of a nuisance parameter. PMID- 8513111 TI - Repeated measurement designs with random selections. AB - We consider repeated measurement designs with a single group as well as with multiple groups. Conventionally, the repeated measurements are made at fixed, often evenly spaced times. The first and second moment conditions needed for an exact F test are not satisfied in general, but with random permutation of the times, a probability measure results that does satisfy these moment conditions, unconditionally. As a consequence, unfortunately, we lose the asymptotic normality that is also essential to justify an F test. We introduce a class of designs and estimators for which both the moment conditions and asymptotic normality are satisfied. The times are the same for all subjects and they are chosen in such a way that they are mutually independent and identically distributed. It is important to understand that our conditions are satisfied only unconditionally--that is, if we do not condition by the randomly chosen times. There is a small probability that the randomly sampled times could be very unevenly allocated. Since we are not conditioning by the times, strictly speaking, this does not matter. It is possible to impose a mild condition of "spread," as we show, at small cost in terms of the P-value. Our method of design makes it possible to do regression analysis, interval estimation, and hypothesis testing on the mean response as a function of time. Because we have mutual independence and identical distributions of times we can form confidence bands. PMID- 8513112 TI - Testing for the existence of a desirable dose combination. AB - We consider the problem of studying several dose combinations of two drugs for a therapeutic endpoint in a multilevel factorial clinical trial. Two test statistics are constructed to test whether there exists at least one dose combination that is more effective than its component doses. Their distributions involve nuisance parameters quantifying the mean differences among the doses of the two component drugs. It is shown that their power functions achieve maxima as all the nuisance parameters approach infinity in absolute value. The significance levels of the two tests are derived and two alpha-level tests are proposed. Tables are given to provide the alpha-level critical values for these tests and to gain insights into their power performances. PMID- 8513113 TI - Nonlinear statistical models for the joint action of toxins. AB - A general approach using nonlinear regression models is presented for evaluating additivity, synergism, and antagonism of mixtures of toxins for proportions and ratio-scale response measures. This approach provides several advantages over the analysis methods typically used, which involve linear regression with logits or probits. A single model fit is performed, rather than a multistep procedure. Nonadditive alternative models can be easily constructed and tested against the appropriate additive models. The approach avoids the use of data "adjustments" for nonzero background response rates. The analyses are performed in the natural response metric, making interpretation straightforward. Also, the nonlinear regression model can be reparameterized to provide more meaningful primary parameters. PMID- 8513114 TI - A theoretical description of non-steady-state diffusion of hydrophobic ions across lipid vesicle membranes including effects of ion-ion interactions in the aqueous phase. AB - A theoretical model of hydrophobic ion diffusion across vesicular membranes is presented, which is based upon activated rate theory. The model is applicable to the sudden addition of hydrophobic ions to a vesicle suspension, for example in a stopped-flow experiment. The time course of diffusion is calculated by numerical integration of differential rate equations for the ion concentrations and electrical potential differences across the membrane. The model utilizes the three-capacitor model of the membrane and an extended Debye-Huckel theory, taking into account non-neutrality on each side of the membrane. At low ionic strengths good agreement is found between the infinite time diffusion potential and the equilibrium Nernst potential. At large excess of inert electrolyte discrepancies are found, but under such conditions the membrane potential is negligible due to screening. PMID- 8513115 TI - Electrophoretic mobility of a "soft particle" with a nonuniformly charged surface layer as a model for cells. AB - The electrophoretic mobility of a colloidal particle with a nonuniformly charged ion-penetrable surface layer in an electrolyte solution (as a model for a biological cell) is calculated for the case in which the surface charge layer consists of two oppositely charged sublayers. It is shown that the mobility and the surface potential (the latter of which is defined as the potential at the front surface of the surface charge layer) generally exhibit different behaviors, in contrast to the case of rigid particles, which is described by Smoluchowski's mobility formula. The mobility in some cases shows a minimum (or a maximum) when plotted as a function of the electrolyte concentration and alters its sign at a certain concentration, which is considered to be an isoelectric point of the mobility with respect to the electrolyte concentration. This isoelectric point is in general different from that of the surface potential. PMID- 8513116 TI - Thermodynamical model of mixed aggregation of intercalators with caffeine in aqueous solution. AB - Recently we presented evidence that some intercalating antitumor agents can form complexes with caffeine and that this process may be responsible for the modifying effect of caffeine on the pharmacological activity of these drugs (F. Traganos et al., Cancer Res. 51 (1991) 3682). Here we describe a statistical thermodynamical model of mixed associations in which one component's self association is limited to dimer formation while the second component has the ability of unlimited stacking. The system is controlled by three parameters which represent self-aggregation "neighborhood" association constants KCC and KAA and a mixed "neighborhood" association constant KAC. The model was tested using acridine orange and light absorption spectroscopy as an analytical method for detection of complex formation. The experiments performed at two NaCl concentrations (0.01 and 0.15 M) indicate interesting properties of the three parameter system in which the first parameter (KCC) is practically independent of ionic strength, the second (KAA) is positively and the third parameter (KAC) is adversely affected by ionic strength. PMID- 8513117 TI - Peptide-urea interactions as observed in diketopiperazine-urea cocrystal. AB - In order to develop a more complete understanding of urea induced protein denaturation we have investigated the crystal structure of urea with the cyclic dipeptide diketopiperazine. This structure, determined to an R factor of 8.1%, shows extensive hydrogen bonding between urea and the peptide groups of diketopiperazine. These studies support a model where hydrogen bonding plays an important contribution in urea-induced protein denaturation. In the companion paper we present thermodynamic data for urea-peptide interactions in aqueous solution that further support this model. PMID- 8513118 TI - Urea-diketopiperazine interactions: a model for urea induced denaturation of proteins. AB - The solubility of diketopiperazine (DKP) in aqueous urea (U) solutions with molalities ranging from 0 to 16 mol kg-1 (corresponding to urea activities ranging from 0 to 10 mol kg-1) has been measured as a function of the urea activity at 298.15 K. In accordance with a previous study the solubility of diketopiperazine increases with increasing urea activity but drops sharply at a urea activity of 5.7 +/- 0.2 mol kg-1. This drop in solubility can be attributed to the formation of a DKP.U2 cocrystal. The solubility data were fitted to a simple model based on the stoichiometry of the DKP.U2 to yield an intrinsic equilibrium constant kappa describing the interactions occurring between a urea molecule and a peptide group of diketopiperazine in aqueous solution, its value being kappa = 0.0447 +/- 0.0007 kg mol-1. When the activity of water is taken into account, kappa has a lower value of 0.0398 +/- 0.0007 kg mol-1. PMID- 8513119 TI - Evaluation of the structural modifications induced by mitomycin C on nucleic acids. AB - The interaction of poly(dG-dC).poly(dG-dC) with mitomycin C, an antitumor antibiotic, has been studied by various spectroscopic methods: circular dichroism, Fourier transform infrared resonance Raman scattering and using fluorescence emission of terbium bound to unpaired guanines as local conformation probe. The results allowed us to confirm the lack of long range modification of the DNA secondary structure upon binding. They also brought first information concerning the modification of the local structure of the nucleic acid at the level of mono- or bifunctional adducts. PMID- 8513120 TI - Denervation impairs cutaneous microvascular function and blister healing in the rat hindlimb. AB - Skin sensory nerve nocifensor functions were investigated non-invasively in rats by measuring neurogenic inflammation and blister healing-rate after unilateral hindlimb denervation. Axon reflexes were evoked by transdermal iontophoresis of acetylcholine (ACh) or noxious electrical stimulation (TNS). Sodium nitroprusside (SNP) evoked direct dilator responses. Resultant changes in skin microvascular blood flux were measured by laser Doppler flowmetry. Compared with their sham operated control limbs, denervation reduced inflammatory responses (ACh or TNS) by more than 85% and SNP responses by 28% (p < 0.05). Healing of dry-ice blisters raised on the hindpaw 14d post-denervation was significantly slower to complete healing (42d) than controls (26d) and initial inflammation was attenuated, confirming that innervation is important for inflammation and blister-healing. PMID- 8513122 TI - Thalamus and neurogenic pain: physiological, anatomical and clinical data. AB - Microelectrode recordings in the medial thalamus of 45 neurogenic pain patients undergoing medial thalamotomy revealed that most units (316/318) did not respond to somatosensory stimuli, and that half exhibited low-threshold calcium spike bursts. After medial thalamotomy, 67% of the patients reached a 50 to 100% pain relief, without somatosensory deficits. Colocalization of bursting activities and of the most efficient therapeutic lesions in the central lateral nucleus suggests a key role of this structure in neurogenic pain. We propose that neurogenic pain is due to an imbalance between central lateral and ventroposterior nuclei, resulting in an overinhibition of both by the thalamic reticular nucleus. PMID- 8513121 TI - Inhibition of the tail flick reflex following microinjection of morphine into the amygdala. AB - Recent evidence indicates that the amygdala plays a critical role in the activation of brain stem antinociceptive systems during stress. In the present experiment, bilateral microinjection of morphine sulfate (10 micrograms) into the amygdala of pentobarbital-anesthetized rats resulted in a time-dependent elevation in latency of the tail flick reflex evoked by radiant heat. The most effective sites within the amygdala were in or immediately adjacent to the basolateral nucleus. The relative amplitude of the tail flick reflex did not differ as a function of repeated testing or morphine treatment. These results suggest that important forebrain inputs which normally activate endogenous antinociceptive systems in behaving animals may be manipulated and studied in detail using the anesthetized rat. PMID- 8513123 TI - Lesion-induced NADPH-diaphorase reactivity in neocortical pyramidal neurones. AB - Pyramidal neurones of the rat neocortex do not normally express NADPH-diaphorase reactivity. However, after stab lesions which extended through the entire depth of the neocortex, strong NADPH-diaphorase reactivity was observed in pyramidal neurones at 7 and 14 days post-lesion. At 3 and 21 days post-lesion fewer and less reactive pyramidal neurones were observed, and no reactive pyramidal neurones were seen at 2 and 26 days post-lesion. The great majority of reactive pyramidal neurones were in layers V and VI and most were situated medial to the lesion. The induction of NADPH-diaphorase implies that the capability to synthesize nitric oxide may be a component of the pyramidal neurones' response to traumatic injury. PMID- 8513125 TI - A70104 and food intake in pigs: implication for the CCK 'satiety' hypothesis. AB - The aim of the present study was to determine whether CCK released from the small intestine during a meal acts as a satiety factor. The effects of the novel CCKA antagonist A70104 (50-200 micrograms kg-1, i.v.) were investigated on operant food intake in 4 h food-deprived pigs. None of the doses used had any significant effects on the amount of food consumed by the animals over the 2 h measurement period. However, pretreatment of the pigs with A70104 (100 micrograms kg-1) did block the inhibitory effect of exogenous CCK (1 microgram kg-1, i.v.) on operant feeding. These results thus question the validity of the hypothesis that endogenous peripheral CCK acts as a satiety factor. PMID- 8513127 TI - Development of a memory trace for a complex sound in the human brain. AB - The development of a memory trace for a complex, unfamiliar sound in the human brain was studied by repeatedly presenting reading subjects with this sound ('standard') which was occasionally replaced by a slightly different sound ('deviant'). Deviants did not elicit the mismatch negativity, an index of automatic change detection in auditory cortex, in the beginning but did later during the session. This result reflects a gradual 'sharpening' of sensory information encoded in the memory trace: the representation of the standard stimulus eventually became precise enough to enable the cortical change-detector mechanism to detect a slight different stimulus. PMID- 8513128 TI - Behavioural abnormalities in a murine model of a human lysosomal storage disease. AB - The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase activity. We now report behavioural abnormalities associated with this single gene defect. In grooming, a developmentally regulated and genetically based activity, the mutant mice spent 1-5% of the normal time for body grooming and about 60% of the normal time in face grooming when stimulated with a light water mist. In the Morris water maze which tests spatial learning, the mutants could learn to locate an invisible platform but were deficient in remembering its location the next day or developing strategies to locate it in new positions. Thus, the gusmps/gusmps mouse demonstrates behavioural, memory and cognitive deficiencies suitable for monitoring functional restorations in therapy. PMID- 8513126 TI - Effect of hypothyroidism on rat peripheral nervous system. AB - The function and structure of the peripheral nervous system of Sprague-Dawley rats, 3 months after the induction of hypothyroidism by administration of N propylthiouracil in drinking water, has been studied. The motor action potential amplitude of the caudal nerve showed a significant reduction (p < 0.001) when compared with an age-matched control group of animals. Computer-assisted morphometric analysis of sciatic nerves of hypothyroid rats showed normal distribution and density of myelinated fibers, and a normal axon/myelin ratio. Electron microscopy revealed only minor alterations in axons of myelinated fibers characterized by a dissolution of neurotubules. After two months of substitution therapy these effects were reversed. The present data suggest that early impairment of nerves induced by hypothyroidism is rare and could be related to metabolic alterations rather than to structural changes and is reversible with hormone treatment. PMID- 8513124 TI - Neuroactive peptides exist in the midbrain dopaminergic neurons that contain calbindin-D28k. AB - Calbindin-D28k, a calcium-binding protein, has been identified within a subpopulation of midbrain dopaminergic (DA) neurons in rats, monkeys and humans. The neuroactive peptides CCK and neurotensin also have been found in a subpopulation of midbrain DA neurons. Using double- and triple-labeling immunocytochemical staining procedures in the rat, we now report that the midbrain DA neurons that contain the peptides also contain calbindin-D28k. Calbindin-D28k may play a role in the co-release of neuroactive peptides with dopamine from the midbrain DA neurons. PMID- 8513129 TI - Distribution of synaptic terminals from prepositus neurones on the collicular maps. AB - The distribution of synaptic terminals was quantified in the superior colliculus (SC) following injections of Phaseolus vulgaris-Leucoagglutinin in the ventral prepositus hypoglossi nucleus (PH) and adjacent reticular formation. Labelled axons distribute terminals within the intermediate and the deep layers on both sides. Within the former, their distribution reproduces the representation of the visual hemifield on the same side as the injected PH. Additionally the density of boutons gradually increases in the contralateral SC, from the projection of the area centralis towards the periphery, i.e. towards regions coding for larger saccades. Such a differential synaptic input may provide the neuronal basis for a temporal to spatial transformation of the feedback signal controlling gaze shifts. A theoretical model is proposed. PMID- 8513130 TI - Intrinsic connections between representation zones in the cat motor cortex. AB - The functional organization of intrinsic connections in the cat motor cortex was examined by combining intracortical microstimulation with neuroanatomical tracers. After single injections of a dye into a cortical site from which wrist flexion was evoked, clusters of retrogradely labeled somata and of anterogradely labeled axon terminals were found throughout the forelimb representation zones. These intrinsic connections rarely involved representation zones of the hindlimb or the face musculature. These data indicate that extensive intracortical connections mediate reciprocal synaptic interactions among groups of cells involved in the execution of different movement segments. These clustered, horizontal connections may be used for coordinating the activity of different cortical representations for the execution of complex movements, and may also be involved in the pliability of motor representation maps. PMID- 8513131 TI - Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25-35. AB - To investigate whether and how amyloid-beta protein (A beta) is involved in the neurodegenerative changes characteristic of Alzheimer's disease (AD), primary hippocampal neurones from foetal rat brain were exposed acutely and chronically to micromolar concentrations of a synthetic peptide homologous to residues 25-35 of A beta (beta 25-35). A single application of this peptide (25-100 microM) was ineffective but when the neuronal cultures were exposed to beta 25-35 (25-100 microM) repeatedly every two days for ten days, cell survival was dramatically reduced. The structural changes and the DNA fragmentation of cells chronically exposed to the peptide suggested that neuronal death occurred by apoptosis. Furthermore, beta 25-35 showed the intrinsic ability to polymerize into amyloid like fibrils in vitro. These results confirm the potential pathogenic role of A beta in AD, and indicate that amyloid fibrils may induce neuronal death through a specific programmed process. PMID- 8513132 TI - Glucocorticoids depress activity-dependent expression of BDNF mRNA in hippocampal neurones. AB - Glucocorticoid hormones are important regulators of brain development and ageing, and can impair the capacity of hippocampal neurones to survive various neurological insults. Here we show that dexamethasone, a synthetic glucocorticoid, prevents activity-dependent increases of brain-derived neurotrophic factor (BDNF) mRNA in cultures of rat hippocampal neurones. In situ hybridization was used to evaluate the levels of BDNF mRNA. Up-regulation of BDNF mRNA triggered by depolarization with high potassium, or exposure to the glutamate receptor agonist kainic acid, resulted both from higher levels of expression in neurones and from new recruitment of cells. These data suggest that the known ability of glucocorticoids to exacerbate neuronal injury following ischaemia and other metabolic insults could be due to antagonism of regulatory mechanisms governing neurotrophin levels in the brain. PMID- 8513133 TI - Carboxyl domain of glutamate receptor directs its coupling to metabolic pathways. AB - Of the six metabotropic glutamate receptors (mGluRs) only mGluR1 and mGluR5, which possess a large carboxyl terminal domain, are positively linked to phosphoinositide (PI) hydrolysis. We expressed a 3' deletion of mGluR1 alpha (mGluR1T) lacking the terminal 290 codons and the full length mGluR1 alpha cDNAs in human embryonic kidney 293 cells. Agonist stimulation of both mGluR1 alpha and mGluR1T stimulated PI hydrolysis. Glutamate activation of PI hydrolysis was reduced by pertussis toxin when mediated via mGluR1 alpha, while mGluR1T required the presence of extracellular Ca2+. Glutamate-mediated reduction of adenylyl cyclase stimulation by forskolin occurred only in mGluR1T-expressing cells. The results suggest that the carboxyl terminal extension directs the coupling of mGluR1 with different signal transduction pathways. PMID- 8513134 TI - In vivo visualization of acetylcholinesterase with positron emission tomography. AB - The cerebral distribution of [11C]physostigmine, an acetylcholinesterase inhibitor, was studied with autoradiography in rats and positron emission tomography in primates. In rat brain [11C]physostigmine radioactivity was exactly superimposable to acetylcholinesterase activity, being highest in the basal ganglia, moderate in the cortex and hippocampus, and low in the cerebellum. In primate brain, the early blood-flow dependent distribution of [11C]physostigmine was followed by a rapid redistribution to acetylcholinesterase-rich regions such as the striatum. The cerebral uptake of [11C]physostigmine was significantly reduced by competition with an excess of unlabeled physostigmine. These results suggest that [11C]physostigmine is a promising new ligand for in vivo imaging of acetylcholinesterase activity with PET. PMID- 8513135 TI - Kainic acid has cell-specific effects on survival of hypothalamic mouse neurones in vitro. AB - Cultures of mouse hypothalamus from embryonic day 15 fetuses were exposed to kainic acid (KA) to study effects on survival of selected cell populations. After 6 days in vitro, immunocytochemistry revealed destruction of dopaminergic and GABAergic neurones after KA-treatment, whereas numbers of oxytocinergic cells and neurones containing metEnkephalin were unchanged. Surviving neurones were characterized by a loss of processes or a reduction of process length. Glial cell numbers did not show any differences between groups. Amino acid concentrations decreased after KA-treatment; only glutamine and taurine levels were unaffected. We conclude that toxic effects of KA differ with respect to distinct neuronal populations of the mouse hypothalamus. Therefore, experimental data concerning neuronal destruction under in vitro conditions have to take into account the selectivity of this neurotoxic agent. PMID- 8513136 TI - Haloperidol increases PPE mRNA levels in the caudal part of the nucleus accumbens in the rat. AB - Dopamine exerts a tonic inhibitory control in the regulation of mRNA encoding preproenkephalin (PPE), the precursor of enkephalin, in the dorsal part of the rat striatum. Less is known about the role of this amine in the regulation of PPE mRNA in the ventral part of the striatum which corresponds to the nucleus accumbens. In this study, the effects of an interruption of dopamine transmission by haloperidol (a dopaminergic receptor antagonist) were examined in the rat nucleus accumbens. The levels of PPE mRNA were analysed by in situ hybridization histochemistry by taking into account the complexity of the nucleus accumbens, i.e. by differentiating the rostro-caudal extension of the structure. It was found that PPE mRNA content was increased significantly only in the caudal part of the nucleus, indicating rostro-caudal differences in the haloperidol effects. The differential reactivity of PPE mRNA to dopaminergic receptor blockade and to a lesion of dopaminergic neurones along the rostrocaudal axis of the ventral striatum is discussed. PMID- 8513137 TI - Alteration of potassium-evoked 5-HT release from virus-infected rat cortical synaptosomes. AB - Potassium-evoked 3H-serotonin (5-HT) release from rat cerebrocortical synaptosomes was performed after peripheral inoculation with fixed rabies virus CVS (challenge virus strain). At the onset of clinical symptoms, the rats were sacrificed, synaptosomes were prepared from dissected cortices and assayed for K+ evoked 5-HT release. The results show a decrease in evoked 5-HT release from virus-infected synaptosomes. Alterations in serotoninergic transmission in rabies virus infected brain cortex indicate a possible involvement in the triggering of pathogenetic mechanisms relating to the clinicopathological manifestations of the viral disease. PMID- 8513138 TI - Nitroprusside improves blood flow and reduces brain damage after focal ischemia. AB - We used the nitric oxide (NO) donor sodium nitroprusside (SNP) and the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) to study the role of NO in the ischemic damage produced by occlusion of the rat middle cerebral artery (MCA). After MCA occlusion, intracarotid administration of SNP (2.5 mg kg h-2 for 1 h) enhanced the recovery of neocortical cerebral blood flow and of the EEG and reduced cortical infarct size by 76 +/- 2% (p < 0.01; n = 5). In contrast, administration of L-NAME (10 mg kg h-2) worsened the recovery of CBF and EEG and increased infarct size (+ 60 +/- 16%; p < 0.05; n = 5). The findings indicate that NO improves blood flow and reduces tissue damage after focal cerebral ischemia. Thus, NO donors could have an important role in the management of acute ischemic stroke. PMID- 8513139 TI - Increased levels of NGF in sera of systemic lupus erythematosus patients. AB - Using a specific enzyme-linked immunosorbent assay (ELISA) for human nerve growth factor (NGF), serum levels in patients with systemic lupus erythematosus (SLE) were measured. We found a consistent increase in NGF levels in SLE patients compared with controls. A good correlation exists between serum NGF level and severity of clinical manifestation. We hypothesize that NGF might play a role in the pathogenesis of autoimmune disorders such as SLE. PMID- 8513140 TI - Delayed production of nitric oxide contributes to NMDA-mediated neuronal damage. AB - Exposure of primary murine cortical neuron cultures to N-methyl-D-aspartate (NMDA) resulted in neuronal death as evidenced by release of lactate dehydrogenase (LDH) into the media. The addition of N-nitro-L-arginine (N-Arg) protected the neurons from death in a concentration-dependent manner when added after the NMDA, but not when the N-Arg was present with the NMDA. Protection by N Arg was lost if L-arginine containing media was added to the cultures prior to the addition of the N-Arg. Treatment of the neurons with kainate prior to NMDA reduced subsequent NMDA-induced damage which was not prevented with N-Arg. These results suggest that delayed production of nitric oxide (NO) contributes to NMDA induced neuronal damage in culture. PMID- 8513141 TI - Paraesthesia elicited by repetitive magnetic stimulation of the postcentral gyrus. AB - Repetitive transcranial magnetic stimulation of short duration (0.3 or 0.6 s, 20 Hz) evoked paraesthesia similar to that caused by repetitive electrical stimulation. Since the points eliciting the paraesthesia were approximately 2 cm posterior from those eliciting motor responses, the paraesthesia stemmed from direct excitation of the post-central gyrus. The paraesthesia showed somatotopical representation: the point eliciting the paraesthesia in the leg was separated from the point eliciting the paraesthesia in the hand 2.9 cm medially in one subject, and 1 cm posteriorly and 1 cm medially in the other subject. Repetitive transcranial magnetic stimulation provides a painless, noninvasive method for mapping cortical sensory representation in humans. PMID- 8513143 TI - Effects of transient spatial attention on auditory event-related potentials. AB - Event-related potentials (ERPs) were recorded in subjects receiving left- and right-ear tones while they shifted attention to the left or right on a trial-by trial basis. ERPs at attended compared with unattended tones revealed an enhanced negativity consisting of an early part that was parietally distributed and a later part with a frontocentral distribution. It may be concluded that these ERP modulations reflect the selection of auditory stimuli according to spatial criteria within a transient spatial attention situation. Furthermore, the attention-related negativity was not reduced for long inter-stimulus intervals (10 s) suggesting that prior stimulus exposure is not a basic requirement for eliciting attention-related negativity in the auditory modality. PMID- 8513142 TI - Indirect coupling of calcium transport in chromaffin granule ghosts to the proton pump. AB - In chromaffin granule ghosts, the Na+/Ca2+ exchanger in the granule membrane can provide a high affinity (Km 1-3 microM) and high capacity (Vmax 50-100 nmol mg min-2) mechanism for Ca2+ accumulation. The activity of the Na+/H+ antiporter can be used to couple Ca2+ uptake via Na+/Ca2+ exchange to ATP-dependent proton translocation via the granule membrane H(+)-ATPase. Therefore, Ca2+ uptake can be indirectly linked to the proton pump. However, under conditions designed to mimic the environment of a granule in the cytosol of a chromaffin cell, measured rates of Ca2+ uptake are low, a free Ca2+ concentration of about 5 microM in the ghost matrix being attained. Under such circumstances, the granules seem unlikely to play a major role in calcium homeostasis in the intact cell. PMID- 8513144 TI - Renin activation correlates with blood amount and distribution in subarachnoid haemorrhage. AB - Blood extent and localization visible in CCT predicts complications and prognosis in patients suffering from subarachnoid haemorrhage (SAH). Plasma renin activity (PRA) elevation is one of the hormonal parameters of autonomic disorders after SAH and its prognostic relevance could be confirmed by this study, too. But the correlation of PRA with blood amount and distribution was the main target of this study. Large amounts of blood are connected with higher PRA-levels and more PRA rises. Even a linear correlation between the amount of blood defined by a CCT score and PRA in ng ml h-2 could be established. A significant correlation was found between intraventricular, suprasellar blood, ventricular enlargement of the third/lateral ventricles and PRA-elevations. Disorders of hypothalamic and/or medullary centres of sympathetic control are thought to be the underlying cause and to depend on blood extent and distribution. PMID- 8513145 TI - Demonstration of cdc2 kinase in mature neuronal nuclei. AB - Immunocytochemistry has been used to assess the distribution of the mitosis associated protein kinase, cdc2, in mature neurons of rat brain. A robust signal is apparent in most, but not all neurons in cerebellum, cortex and hippocampus. The signal is concentrated in neuronal nuclei with lower levels of immunoreactivity in neuronal cytoplasm. High resolution analysis indicates that the amount of cdc2 is uneven, suggesting that regulated amounts of enzyme may reflect different functional status of the neurons. In many cases, the kinase is concentrated at the nuclear periphery, implying that it may be particularly involved in phosphorylating substrates in this subnuclear compartment. These results indicate additional roles for cdc2 in terminally differentiated neurons which have undergone final mitosis. PMID- 8513146 TI - Genetic analysis of nucleotide excision repair in mammalian cells. AB - Nucleotide excision repair is a versatile process and is one of the best known systems that prevents the deleterious consequences of DNA damage induced by environmental agents and cellular metabolites. Without repair, persisting lesions can interfere with proper functioning of DNA-metabolizing processes, notably transcription and replication, and give rise to mutations. The effect of inefficient or deficient repair is illustrated by genetic repair diseases that predispose individuals to cancer due to the fact that mutations accumulate at a high rate. Here we describe the progress that has been made from the initial cloning and characterization of nucleotide excision repair genes to the current understanding of their function in the complex nucleotide excision repair process. PMID- 8513147 TI - The induction of gene expression in mammalian cells by radiation. AB - A large number of genes have now been shown to be inducible in response to radiation in mammalian cells and tissues. Based on extensive studies of stress inducible regulons in bacteria, it is assumed that at least some of the proteins encoded by these genes are involved in an adaptive response to the lethal effects of radiation. Here I review the biological evidence for adaptation, and analyse the functions of radiation inducible genes in the context of their possible roles in cellular protection. Recent progress has been made in understanding how cells sense radiation induced damage. The signal transduction pathways which end in the activation of specific genes is summarized. PMID- 8513148 TI - Cell cycle checkpoints, genetic instability and cancer. AB - During the cell cycle, the order of events is maintained by controls termed checkpoints. Two checkpoints are sensitive to DNA damage, one that acts before mitosis and a second that acts before DNA replication. This is relevant to cancer because checkpoint mutants show genetic instability, and such instability is characteristic of many cancers. Studies of checkpoints in normal and cancer cells suggest a mechanistic relationship to the central cell cycle control p34CDC2 and its regulators. We suggest how mutations in these genes and those with a role in DNA metabolism may affect the function of checkpoints. A further link between checkpoints and cancer may be the p53 protein, which appears to function at the G1-S checkpoint. Consideration of checkpoints may provide more effective means for cancer treatment. PMID- 8513149 TI - The repair of ionising radiation-induced damage to DNA. AB - Exposure of DNA to ionising radiation produces a variety of lesions. Double strand breaks are repaired by recombinational pathways including a rapid single strand annealing process which results in deletion of DNA sequences, and a double strand break repair pathway which conserves genetic information. Single-strand breaks are repaired by the sequential action of a 3'-phosphodiesterase, DNA polymerase beta and a DNA ligase. Damaged bases are excised by DNA glycosylases, and a single-base gap introduced, either by the action of an AP endonuclease activity and a DNA deoxyribophosphodiesterase, or by the AP lyase activity of the glycosylase and an AP endonuclease. Repair is completed by DNA polymerase beta and a DNA ligase. PMID- 8513150 TI - DNA double-strand breaks and the RAD50-RAD57 genes in Saccharomyces. AB - The yeast Saccharomyces provides a powerful system for investigating the biological effects of ionizing radiation, and studies have identified double strand breaks in DNA as probably of critical importance in determining lethality. These breaks are normally repaired by a recombinational mechanism, but in the absence of repair a single break may be lethal to the cell. Genetic and molecular analysis of the eight genes known as RAD50 to RAD57 has revealed much about recombinational repair. These genes are also of central importance in other processes including meiosis and may be of general significance in understanding radiation responses in eukaryotes. PMID- 8513151 TI - Molecular biology of mutagenesis of mammalian cells by ionizing radiation. AB - In mammalian cells, ionizing radiation induces comparable numbers of point mutations (principally base changes, frameshifts and small deletions) and of large deletions of more than a hundred base pairs. The latter are formed either by misrepair of an end from one double-strand break with an end from another, or by a second mechanism which, it is suggested, is initiated by slowly repaired single-strand nicks. The ratio of deletions to point mutations is variable from one gene to another, and is greatest for genes in which very large deletions still allow cells to survive. PMID- 8513152 TI - A critical look at the association of human genetic syndromes with sensitivity to ionizing radiation. AB - Individuals with inherited heterozygosity for mutations involving tumor suppressor genes may be at greater risk for ionizing radiation-induced cancer even though their cells may not show increased cytotoxicity or chromosome damage. In addition, many human genetic syndromes have been reported to show increased sensitivity to ionizing radiation. In most instances the effects are small and/or not reproducible. Only in the genetic disease ataxia-telangiectasia (AT) is radiosensitivity consistently outside the normal range. Even AT heterozygotes (0.68 to 7.7% of the population) appear to be slightly radiosensitive, and their elevated cancer risk may result from exposure to ionizing radiation. Current research has concentrated on the isolation of the gene or genes responsible for this disease. PMID- 8513153 TI - [Quality of health care and costs]. AB - The quality of health care is largely discussed issue among health care professionals in Finland. The purpose of this article is to point out some relations between the quality of nursing and the economical costs. The theme is mostly ignored in the published articles and books about quality of nursing and health care. In the previous studies of quality of nursing four main approaches have been introduced 1) practical approach, 2) professionalism, 3) client orientation and 4) research orientation. An important weakness in the approaches is that they are carried out from a point of view of a single profession at the time. Really multiprofessional projects are the exception. Additionally, economic costs have not been included in nursing quality concept or evaluation criterion. The need for quality in any health services is urgent, including nursing. That is because of decreasing resources and changing market oriented steering mechanisms in the Finnish health care system. In this situation the quality of nursing may arise as one important competition factor in the organizations and the units. The costs of poor quality of nursing are not well recognized among professionals. Collaboration between different professionals is a key issue to solve these kind of problems. We need more research about the relations between economic factors and quality of nursing and other health services. PMID- 8513154 TI - [Health-related quality of life measures]. AB - This article highlights reasons, why generic and standardised measures of health related quality of life are needed. It discusses briefly the methodological steps required in developing such a measure. As an example a generic 15 dimensional measure of health-related quality of life (15D) is introduced and experiences gained from its use are described. In principle, the measure defines billions of mutually exclusive 15 dimensional states. The experiences gained suggest 15D to be reliable, widely applicable, practical and easy to use. The measure provides a convenient tool for repeated measurement of health-related quality of life. The two-stage valuation method applied for deriving the values for 15D dramatically simplifies the valuation process and makes the task easier than the traditional direct valuation methods. Finally, examples of projects, where 15D is or has been applied, are given. PMID- 8513155 TI - [Are clients' well-being and everyday life starting points in nursing practice?]. AB - In this paper the goal of nursing and nursing care are explored from the point of view of clients and nurses. The basis of this text is on PhD, dissertation Health, wellbeing and nursing as experienced by municipal residents and nurses (see Astedt-Kurki 1992b). The aim of that study was to gain more information on people's individual health and of the possibilities of nurses working in Finnish primary health care have in supporting their clients. The experiences of health as results of the study reveal individual meanings. Clients' expressions of health contain different kinds of values of good life, eg. peace, freedom, religiousness, humour, human relations etc. Everyday-life experiences of health in this study are feelings of health, knowledge about one's state of health and action, eg. personal self-care. There are differences in views of health and nursing between clients and nurses. It seems that nurses view clients' health also in a disease-oriented manner although there are efforts to client-centered nursing. Nurses did not describe eg. religiousness as a part of clients' health and wellbeing. Another example of the differences between conceptions of nurses and clients is health education, which mostly in nursing care is based on general knowledge of health as opposite of disease without taking into consideration the client's personal life and situation. If the basic interest of nursing practice is eliminating diseases, nursing care is usually carried out by performing different tasks on clients. Part of the nursing care is client-oriented nursing. Awareness of the significance of health and wellbeing in human life helps nurses taking care of their clients individually. PMID- 8513156 TI - [Development of the nursing profession]. AB - In Finland nursing has been seen as an encounter between a nurse and a client or a patient. It is necessary to see nursing from the wider point of view and the wholeness of the profession it consists. There are at least three universal dimensions. They are: to fulfill the basic task of nursing, the development of nursing discipline and the development of the profession. The profession cannot be developed without a strong commitment in the task of nursing this commitment and its improvement being the most important challenge of nursing. The commitment is followed by responsibility, collegiality and collectivity as means to achieve the mutual goal. It is important to achieve the professional nursing education, which means university education. This kind of education is necessary because it provides ability to keep up with scientific studies, to apply the results of the studies to do research work. The education of nursing leaders also must be the kind it provides with ability to commit oneself to development of nursing and nursing research on one's own area, and managing nursing from the point of view of the knowledge base of nursing discipline, i.e. from the leadership and management theories of nursing. PMID- 8513157 TI - [Quality assurance today and some future perspectives]. AB - The purpose of this article is to describe the developmental level of QA in Finland. Working unit, regional and national level QA activities are reflected. The major effort to study the current situation of nursing QA was taken by STAKES (The National Research and Development Centre for Welfare and Health) in the beginning of 1993. Over 1200 institutions received a questionnaires where their QA activities were inquired. The increasing need for multiprofessional cooperation, better information and participation of nursing care personnel are discussed. To utilize research findings and to increase resources and skills of nursing care personnel to perform small scale studies are seen essential for QA advancement. To receive good quality care is a right of all patients. The nursing care personnel is responsible to deliver that kind of care. QA is a means to provide it. Accountability is demanded by both public and profession itself. Nurses have taken the leadership in providing good quality nursing care. PMID- 8513158 TI - Depressive changes in stroke patients. AB - The present state of research concerning depressive alterations following cerebrovascular infarcts is reviewed with special consideration of methodological issues, the course of depressive changes and interactions with neuropsychological and clinical parameters. The concepts of 'grief response', '(depressive) catastrophic reactions' and 'post-stroke depression' are analysed and compared. An attempt is made at a theory of post-stroke depressive alterations that is based on neuroanatomical, pathophysiological and neurochemical models of depression and psychosocial changes and interactions. Therapeutic implications are discussed. PMID- 8513159 TI - Acute lymphoblastic leukaemia: language deficits in children post-treatment. AB - The language abilities of a group of 22 children (aged between 5 years and 17 years, 9 months) treated for acute lymphoblastic leukaemia (ALL) were investigated and compared with those of a group of non-neurologically impaired, age- and sex-matched controls. The language test battery included an age appropriate measure from the Test of Language Development (TOLD) series, consisting of either the Test of Adolescent Language (TOAL--2), or the Test of Language Development--Intermediate or --Primary (TOLD--I or --P); the timed subtests of the Clinical Evaluation of Language Function (CELF); the Boston Naming Test; and one of either the Token Test or the Token Test for Children, depending on the age of the subject. As a group, the leukaemia subjects performed significantly worse than the controls on the TOAL--2, TOLD--I, TOLD--P, Token Test, and Boston Naming Test. The need for post-treatment monitoring of the language abilities of children treated for ALL to enable early remediation of areas of deficit is highlighted. PMID- 8513160 TI - Reliability of the diagnosis of impairments in survey research in the field of chiropody. AB - Chiropody is a rather unknown paramedical profession in The Netherlands. A chiropodist treats foot and nail problems or postural deviations which may be corrected by means of remedial foot therapy. There is no history of scientific research on chiropody. A necessary first step is a survey on professional practice, diagnosis and treatment. A requirement for a survey study is a reliable registration form. In this study a registration form that draws on the conceptual framework of the ICIDH (International Classification of Impairments, Disabilities and Handicaps) was tested on inter-observer reliability. A chiropodist and a trainee examined 49 patients. Reliability was determined using two measures: the percentage of agreement and Cohen's Kappa. Findings of this study indicate that the reliability of the registration form for the assessment of the chiropody diagnosis is satisfactory. PMID- 8513161 TI - Community-based rehabilitation--a survey of disabled in a village in Botswana. AB - The present study was undertaken in the context of developing community-based rehabilitation (CBR) in Botswana. A door-to-door survey was conducted in Moshupa village during 1990, identifying 1.4% disabled persons. Twenty-two per cent of the disabled were younger than 15 years of age and 17% were more than 65 years old. A high proportion (30%) of disabled persons had parents who were related to one another. A majority of the disabled had difficulties with mobility (65%) and 21% had two or more disabilities. Thirty-four per cent received treatment (predominantly modern medicine) and there was a positive association between treatment and education. The results are compared with other disability studies and discussed with reference to the CBR programme aims. PMID- 8513162 TI - Rehabilitation of the elderly patient with stroke: an analysis of short-term and long-term results. AB - All 104 patients, aged 65 years and older, admitted to our rehabilitation unit during the years 1984-1987 were studied. It was the objective to get data on the extent of hospital care, functional outcome and the situation of living 2-5 years after discharge. During inpatient rehabilitation, an equal improvement in activities of daily living (ADL) for patients 65-74 years of age as well as for patients older than 75 years was found. In spite of these findings, older patients had to be discharged to institutional care more often than younger patients. Furthermore, the old patient group had a greater drop of functional abilities at the time of follow-up than the young patient group. Of the 86 patients originally returning home, 84% were still living at home or had been living at home when death occurred, whereas only 16% had been admitted to institutional care during the follow-up period. At the time of follow-up, two thirds of the surviving patients assessed their health status as equal or improved, compared with the time of discharge. In our patients, deterioration of health status was predominantly due to causes other than the original stroke. PMID- 8513163 TI - Functional status in primary care: COOP/WONCA charts. AB - This paper reviews the development in defining and measuring the patient's functional status. It reflects the work of an international working party. Functional status is defined as: 'the ability of a person to perform and adapt to the individual's given environment, measured both objectively and subjectively over a stated period of time'. The Dartmouth COOP Functional Health Assessment charts/WONCA (COOP/WONCA charts) are the adaptation for international use in (general) practice of the Dartmouth COOP Functional Health Assessment Charts. They cover the domains of Physical Fitness, Feelings, Daily Activities, Social Activities, Change in Health and Overall Health, providing a generic, patient oriented instrument. They have been extensively used in chronic diseases, where their acceptability to patients and clinical validity were satisfactory. Their limitations (particularly the quantification and exact interpretation of the scales) do warrant further study. Nevertheless, general practitioners and others are encouraged to use the COOP/WONCA charts. PMID- 8513164 TI - Orocaecal transit-time by the H2 method: effects of definitions of caecal entry and test meal. AB - The study compares common variants of the hydrogen breath test to measure oroceacal transit time under different conditions. Definition of caecal entry point rather than procedural parameters were found to be a main variable influencing the test results. Visual assessment still seemed to be the most reliable and valid technique. To overcome its subjectivity and evaluator dependency, a comprehensive set of rules simulating implicit criteria of expert physicians was defined and compared with commonly used caecal entry assessment rules. Results indicated that: 1) using visual assessment, experts produce highly consistent CE points; 2) caecal entries by the new rule set correlate highly with them, while previously published caecal entry detection methods were poorly correlated with visual assessment; 3) using a semiliquid test meal reduced reliability of all methods, but the new method remained superior; 4) earlier caecal entry detection methods failed completely when early peaks or baseline fluctuations were present; 5) detection of H2 non-producers and of bacterial overgrowth was much more difficult with classical caecal entry definitions than with the new rule-set. PMID- 8513165 TI - Evaluation of Helicobacter pylori sensitivity to amoxycillin and metronidazole in dyspeptic patients. AB - We evaluated the "in vitro" sensitivity to amoxycillin and metronidazole of 193 Helicobacter pylori strains isolated from the gastric mucosa of dyspeptic patients. Susceptibility was determined by disc diffusion on agar plates. All the isolates were found to be sensitive to amoxycillin. On the contrary, 12% of the strains isolated from patients never treated for Helicobacter pylori infection and 73% of those isolated from patients who had previously received unsuccessful treatment for Helicobacter pylori infection were found to be resistant to metronidazole. Resistance was more common in women (17%) than in men (4%: p < 0.01) and was not correlated with age. The occurrence of Helicobacter pylori resistance to metronidazole is relatively common in Italy. In vitro testing of Helicobacter pylori sensitivity seems to be important before embarking on treatments aimed at eradicating the bacterium. PMID- 8513166 TI - Small bowel angiodysplasia: usefulness of peroperative enteroscopy. AB - In this report the Authors present the case of an old patient treated for chronic recurrent bleeding from small bowel angiodysplasia. The diagnosis was missed by the conventional methods: angiography and scintiscan with marked erythrocytes. Diagnosis was instead possible by using intraoperative enteroscopy. The Authors stress the usefulness of this technique that permits the exploration of the mucosal by trans-illumination to discover bleeding and vascular anomalies of the bowel. PMID- 8513167 TI - Stable isotope methodologies in studying human amino acid and protein metabolism. PMID- 8513169 TI - Mathematical modelling of amino acid-derived urea synthesis. PMID- 8513170 TI - Glucagon and amino acid disposal in normal man and in patients with cirrhosis. PMID- 8513168 TI - Ammonia and glutamine metabolism during liver insufficiency: the muscle-gut-liver axis. PMID- 8513172 TI - Diffraction contrast near heterostructure boundaries--its nature and its application. AB - Two phenomena of diffraction contrast arising at or near III-V compound heterostructure boundaries are described and quantitatively analyzed. In the first observation alpha/delta-fringe contrast at boundaries inclined to the electron beam is discussed. Theoretical fringe profiles are generated according to the theory by Gevers et al. in 1964, which are then compared with experimental profiles. Applications to the characterization of AlGaAs/GaAs and InGaAsP/InP interfaces regarding composition, abruptness, and lattice tilt are presented. In the second study a new and very sensitive characterization technique for the direct determination of the strain in strained-layer structures is described. The method uses electron microscope images of 90 degrees-wedges, which exhibit a shift in the thickness contours due to strain relaxation at the edge, and compares these to images which are obtained theoretically by implementing finite element strain calculations in wedges in the dynamical theory of diffraction contrast. The considerable potential of this method is demonstrated on the strain analysis of strained GaInAs/GaAs structures. PMID- 8513171 TI - The Italian Consensus Conference on duodenal ulcer treatment. PMID- 8513173 TI - Instrumentation, techniques, and applications of electron microscopy in the solid state physics group at Glasgow University. AB - This review discusses some of the work performed by the Solid State Physics Group at Glasgow University. A major aim of the group is to obtain quantitative information with high spatial resolution and to do this reliably requires a thorough understanding of both the instrumentation and the interactions between the electron beam and the specimen. Thus the first part of the review discusses those aspects of instrumentation and techniques that the group has considered in detail while the final part deals with applications which involve the study of a wide range of materials covering metallurgical, semiconductor, organic, and magnetic systems. In all these applications, the results from a range of techniques have been required to provide as complete a picture of the material as possible. PMID- 8513174 TI - Microanalysis near particles and voids at grain boundaries. AB - Some of the problems of using high spatial resolution microanalysis in the vicinity of particles and voids in metal grain boundaries are discussed. New analytical results are presented for nickel based alloys, which suggest that elemental distributions in the region immediately adjacent to growing grain boundary particles and voids are often anisotropic. PMID- 8513175 TI - Electron microscopy of materials at the University of Birmingham. AB - The School of Metallurgy and Materials has traditionally put transmission electron microscopy (TEM) in the forefront of its research interests and, through support from SERC and from the university, has always had the facility to carry out state of the art electron microscopy of materials. In this brief review some of the topics where TEM has played a central role in recent work in Birmingham will be described so that it will be seen just how central to the work in Birmingham TEM has been. PMID- 8513176 TI - An analytical electron microscopic investigation of precipitation in an Al-Cu-Zn Mg-Ag alloy. AB - The distribution, morphology, chemistry, and crystallography of the precipitates formed during aging of an Al-Cu-Zn-Mg-Ag alloy have been studied using analytical transmission electron microscopy. The first precipitates to appear during aging at 150 degrees C were thin hexagonal-shaped plate-like precipitates which formed on the (111)Al planes. These precipitates had a face-centred orthorhombic crystal structure and their composition was essentially CuAl2 although they contained a trace of silver. At peak hardness the microstructure consisted of the plate-like precipitates on (111)Al planes and theta' precipitates on (100)Al planes. Overaging resulted in the precipitation of equilibrium theta, CuAl2, which exhibited a lath morphology and an orientation-relationship with the matrix (210)Al magnitude of (110)gamma; (001)Al misoriented from (001)gamma by approximately 6 degrees. Prolonged overaging at 250 degrees C resulted in the formation of cuboid-shaped Al5(Cu,Zn)6Mg2 precipitates which had a cubic crystal structure and a cube:cube orientation-relationship with the matrix. PMID- 8513177 TI - Inner city health: an overview. PMID- 8513178 TI - Whom do we serve? PMID- 8513179 TI - Prenatal care in the inner-city: a cooperative effort. AB - PAHCF and Women and Infants Hospital have been working together for many years to provide high quality, accessible prenatal and obstetrical care to low-income, inner-city residents in the Providence area. Many of these patients have multiple medical, social, and nutritional problems that place them at increased risk for poor pregnancy outcomes. The PAHCF sites offer convenient locations, evening hours, and culturally-sensitive, bilingual staffs; together the five sites provided prenatal care to nearly 1200 patients last year. Women and Infants Ambulatory Care Department provided prenatal care to an additional 1800 women in 1991, including all high risk patients referred for complications or diagnostic evaluations. All patients deliver at Women and Infants, then return to their original source of care for postpartum followup and family planning services. Patient records are readily transferred between the sites, eliminating the need for unnecessary duplication of information or laboratory tests. This close collaboration is mutually beneficial to both the health care providers and the patients whom they serve. PMID- 8513180 TI - Inner-city pediatrics: perspectives on access. PMID- 8513181 TI - School-based health care: an inner-city experience. PMID- 8513182 TI - Inner-city asthma: an allergist's perspective. PMID- 8513183 TI - Inner-city breast and cervical cancer screening: a cooperative report. PMID- 8513184 TI - Domestic violence: an inner-city perspective. PMID- 8513185 TI - Health risk behaviors of urban black and Hispanic residents in Rhode Island. PMID- 8513186 TI - Pompholyx: a still unresolved kind of eczema. PMID- 8513187 TI - Regression and disappearance of clinical symptoms in some cases of genodermatoses. AB - Genetic skin diseases are usually thought of as stable phenotypes caused by a mutant gene. However, a review of the literature on genodermatoses and my personal experience with a number of these disorders show that the concept of a stable phenotype is not always true. A number of genodermatoses actually show a regression of symptoms. Among these are monilethrix, several types of erythrokeratoderma, several forms of palmoplantar keratoderma such as the varians Wachters type and the Richner-Hanhart syndrome, and some forms of epidermolysis bullosa, for example the Dowling-Meara type. Three different reasons possibly underlying the regression of symptoms in genetic diseases are briefly discussed: (1) environmental factors, (2) hormonal influences and (3) movable, transposable elements causing instability of the genome. PMID- 8513188 TI - Generalized eczematous skin rash possibly due to HMG-CoA reductase inhibitors. AB - We report on 3 patients who developed a generalized eczematous skin rash under treatment with simvastatin and pravastatin for hypercholesterolemia. These drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and suppress cholesterol synthesis in the liver. Based on experimental data from the literature that showed eczematous changes in mice treated topically with the HMG CoA reductase inhibitor lovastatin, we suspect that the rash observed in our patients may be a consequence of skin barrier dysfunction following inhibition of cholesterol biosynthesis. PMID- 8513189 TI - Treatment of closed comedones--comparisons of fulguration with topical tretinoin and electrocautery with fulguration. AB - Two consecutive studies were performed with the aim of clearly defining the optimal physical treatment for closed comedones. The first 10 patients with clinically significant numbers of facial comedones were treated with fulguration under EMLA anaesthesia on one side of the face and topical tretinoin on the opposite side. At the end of the study fulguration was shown to be significantly (p = 0.005) superior to topical tretinoin. A direct comparison of light electrocautery using EMLA anaesthetic with fulguration without anaesthesia was then performed on 12 patients. The comedones were subdivided by size into those that were approximately 1 mm or less in diameter and those of greater dimensions. In the treatment of larger comedones electrocautery was shown to be significantly superior to fulguration (p = 0.025), but there was no significant difference in the efficacy of the treatments for the smaller lesions. PMID- 8513190 TI - General practitioners' workload after skin cancer/melanoma screening clinics in The Netherlands. AB - We studied the workload of the general practitioner after two skin cancer screening clinics in the Netherlands. Thirty-one physicians participated in the project. The numbers of patients presenting with benign and malignant skin lesions were recorded 2 weeks before and 6 weeks after the public campaigns. In the week immediately after the screening there was a small increase in the number of consultations for suspected skin cancer. Thereafter, the weekly number of malignant lesions decreased to precampaign levels. Subsequently to the campaigns the numbers of referrals for benign skin lesions decreased slightly. We conclude that the extra workload for the general practitioner generated by the screening campaigns has been negligible. PMID- 8513191 TI - Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus. AB - We report the case of a previously healthy 54-year-old woman, without any family history, who developed an angioneurotic edema with acquired C1 inhibitor deficiency and systemic lupus erythematosus. The search for a lymphoproliferative disorder was negative. Hydroxychloroquine therapy induced simultaneous resolution of lupus and angioedema. The pathophysiology of this association is discussed. PMID- 8513192 TI - Subcutaneous emphysema and pneumomediastinum following dental extraction. AB - A case of acute subcutaneous emphysema of the lateral region of the neck is described. The patient, a 26-year-old woman, also had radiologic evidence of pneumomediastinum. She completely recovered in a few days under prophylactic antibiotherapy. In this case, subcutaneous and mediastinal emphysema was most probably due to the introduction of air into the soft tissue during dental surgery using compressed air equipment. PMID- 8513193 TI - Chordoma with multiple skin metastases. AB - We report a case of sacral chordoma with numerous skin metastases. Histologically they show the typical 'physaliform cells' expressing simultaneously cytokeratin, S-100 protein, epithelial membrane antigen and vimentin immunoreactivity. PMID- 8513194 TI - Cutaneous manifestations in Kartagener's syndrome: folliculitis, nummular eczema and pyoderma gangraenosum. AB - We report the case of a 47-year-old male with Kartagener's syndrome (KS; situs inversus, bronchitis and sinusitis) who showed three types of cutaneous lesions: recurrent outbreaks of nummular eczema, recurrent deep folliculitis and two episodes of pyoderma gangraenosum. The patient had also IgA gammopathy of undetermined significance. This is the second case of KS associated with cutaneous lesions published so far and suggests that primary ciliary dyskinesia syndromes may have skin symptoms. PMID- 8513195 TI - Skin lesions due to treatment with simvastatin (Zocor) PMID- 8513196 TI - Anti-beta 2-glycoprotein I antibodies in Sneddon's syndrome. PMID- 8513197 TI - BCG-vaccine-induced lupus vulgaris and urticarial vasculitis. PMID- 8513198 TI - Immunotherapy of atopic dermatitis by injections of antigen-antibody complexes. PMID- 8513199 TI - Perspectives for immunization of HLA-A1 patients carrying a malignant melanoma expressing gene MAGE-1. AB - Many human melanoma tumors express antigens that are recognized in vitro by cytolytic T lymphocytes derived from the tumor-bearing patient. A gene has been identified that directs the expression of antigen MZ2-E on a human melanoma cell line. This gene, which has been named MAGE-1, shows no similarity to known sequences and belongs to a family of at least 3 closely related genes. Gene MAGE 1 is expressed in approximately 40% of melanoma tumor samples and by some tumors of other histological types. No expression has been observed in a panel of normal tissues. Antigen MZ2-E appears to be presented by HLA-A1, a HLA type found in approximately 25% of the population. Thus, precisely targeted experimental immunotherapy directed against antigen MZ2-E could be provided to individuals identified as HLA-A1 and MAGE-1 positive by HLA typing and analysis of the RNA of a small tumor sample. PMID- 8513200 TI - High-grade pleomorphic T cell lymphoma with restricted involvement of skin and bone marrow. AB - Pleomorphic T cell lymphoma of the medium to large cell type expressing CD30 antigen is a most aggressive peripheral T cell lymphoma. Currently, there is no satisfactory treatment available for this neoplasm. We report the case of a woman with prominent skin and bone marrow involvement without detectable lymph node localization. This unusual presentation of disease responded well to polychemotherapy combined with autologous bone marrow transplantation. PMID- 8513201 TI - Subungual chronic radiodermatitis. AB - We report a patient who developed a subungual radiodermatitis 25 years following radiotherapy for a verruca of the lateral nail fold. The different stages and the treatment of chronic radiodermatitis of the nail apparatus are described. We want to emphasize the late onset of such lesions and the prime importance of the anamnesis. PMID- 8513202 TI - Cerebriform intradermal nevus. A clinical pattern resembling cutis verticis gyrata. AB - A clinical case resembling cutis verticis gyrata due to a cerebriform intradermal nevus (CIN) is reported. Such a lesion is diagnosed on clinical and histopathological grounds. Some aspects are particularly discussed, such as complications of CIN, including the potential development of malignant melanoma, prognosis and different possibilities in the therapeutic approach. It is stressed that early diagnosis, broad surgical excision and plastic reconstruction are major issues. Different techniques of surgical extirpation and scalpflap reconstruction are presented. PMID- 8513203 TI - Histopathological aspects of myiasis. AB - Myiasis, a rare infestation caused by mainly tropical fly larvae, is now more often encountered in Europe, because of the increasing intercontinental trips. A recent case allowed us to study some anatomopathological and entomological aspects of the African fly maggot. PMID- 8513204 TI - Neurotrophic ulcer following Wallenberg's syndrome. AB - A 61-year-old man consulted for two long-standing ulcerations on the scalp and one on the nose, following an acute vascular disorder of the brain stem (Wallenberg's syndrome). The aetiology and pathogenesis of neurotrophic ulcers are briefly discussed. PMID- 8513205 TI - Chronic arsenicism: criminal poisoning or drug-intoxication? Report of two cases. AB - We report two cases with chronic arsenicism. The first one is a young 37-year-old woman who presents leucomelanoderma, plantar keratoderma, polyneuropathy of the legs and transversal striae of the nails. After investigations, criminal intoxication with arsenic caused by her own sister was discovered. The second case is a 42-year-old man who had developed plantar keratoderma, arsenical keratoses and two squamous cell epitheliomas 10 years after a 2-year treatment with Fowler's solution for androgenetic alopecia. PMID- 8513206 TI - Erythema chronicum migrans: an electron-microscopic study. AB - Spirochaetal organisms are found in skin specimens obtained by biopsy from a erythema chronicum migrans lesion. The histological picture shows a logical localization of a lymphohistiocytic cell infiltrate: deep dermal in the central papule and superficial in the erythematous border. The electron-microscopic characteristics of the micro-organisms in these specimens (regular waving appearance with coils every 0.8-1.2 microns, oblique striation of periplasmatic fibrils, cross-section of 0.3 micron, membranes) correspond to the spiral-like structure of Borreliae isolated from blood. The Borreliae seem to move freely through the matrix of the dermis and are not phagocytized. This brings on the typical clinical picture of the centrifugally spreading erythematous band. PMID- 8513207 TI - Basal cell nevus syndrome and congenital hydrocephaly. AB - A case of basal cell nevus syndrome or Gorlin's syndrome is reported in a newborn. The skin condition is associated with congenital hydrocephaly and skeletal malformations. To our knowledge, this is the first case of basal cell nevus syndrome with skin tumors present at birth and localized on the fingers. PMID- 8513208 TI - Hepatic chemoembolization: safety with portal vein thrombosis. AB - PURPOSE: Nine patients with unresectable hepatic malignancy and portal vein thrombosis underwent hepatic chemoembolization. PATIENTS AND METHODS: Six patients had primary malignancies (hepatocellular carcinoma in five, hepatoblastoma in one), and three had metastatic tumor (adenocarcinoma of the colon in two, glucagonoma in one). Chemoembolization was performed with 10 mg/mL of cross-linked collagen, 10 mg/mL of mitomycin, 3 mg/mL of doxorubicin, and 3 mg/mL of cisplatin. Each patient was treated until flow in the hepatic artery ceased completely. RESULTS: All treatments were technically successful. Eight patients responded to treatment, including two long-term survivors (> 2 years). One patient died 31 days after treatment of progressive hepatic malignancy and atherosclerotic disease. No patient developed hepatic infarction or insufficiency as a result of treatment. Follow-up ranged from 1 to 26 months (mean, 13 months). CONCLUSION: Portal vein thrombosis should not be considered an absolute contraindication to hepatic chemoembolization. Hepatic chemoembolization can be performed safely in the presence of adequate collateral circulation. PMID- 8513209 TI - Effectiveness of transcatheter embolization in the control of hepatic vascular injuries. AB - PURPOSE: The authors describe their 11-year experience with transcatheter embolization (TCE) in the treatment of patients with hemorrhagic hepatic injuries. PATIENTS AND METHODS: Twenty-eight TCE procedures were performed in 24 patients between 1980 and 1991. Injuries in 21 patients were due to vehicular or criminal trauma; in three patients, injuries were iatrogenic. There were 21 male and three female patients (age range, 6-64 years). All patients underwent angiography and had evidence of active hemorrhage, pseudoaneurysm, or arteriovenous fistula (AVF). All embolizations were performed with use of Gianturco coils, microcoils, or gelatin sponge. RESULTS: TCE was technically successful in occluding hepatic vascular lesions in 21 of 24 patients (88%). Technical failures were due to the inability to select the appropriate vessel for embolization in two cases and due to a persistent AVF that did not occlude despite further attempts at embolization. Lesions recurred in two patients who underwent initially successful TCE. Both patients were treated effectively with repeated TCE. Only two catheter-related complications were encountered, both after successful TCE. Twenty-one patients survived to be discharged from the hospital. Two patients among the group treated successfully and one from the group in whom treatment failed died. CONCLUSION: This experience demonstrates that TCE is effective in the management of hepatic vascular injuries due to trauma. PMID- 8513210 TI - Massive hemobilia resulting from gallstone erosion of the cystic artery: percutaneous transcatheter embolization as a temporizing measure--case report. PMID- 8513211 TI - Hemorrhagic cholecystitis with hemobilia: treatment with percutaneous cholecystostomy and transcatheter urokinase. PMID- 8513212 TI - Migration of a biliary Wallstent into the duodenum. PMID- 8513213 TI - Standard for diagnostic arteriography in adults. Standards of Practice Committee of the Society of Cardiovascular and Interventional Radiology. PMID- 8513214 TI - Effects of central venous catheter placement on upper extremity duplex US findings. AB - PURPOSE: The upper extremity veins of 17 patients who underwent operative central venous catheter placement were studied prospectively with color duplex sonography to determine which duplex changes, if any, could be due to the presence of the catheter alone and to determine if these waveform changes could mimic the dampened waveform seen peripheral to central nonvisualized or nonocclusive thrombosis or proximal stenosis. PATIENTS AND METHODS: The subclavian, internal jugular, and brachiocephalic veins were examined with color duplex sonography immediately before and after catheter placement. Images obtained before and after catheterization were reviewed by two radiologists for (a) spectral broadening in both the vein of insertion and the brachiocephalic vein, (b) transmission of atrial pulsations, and (c) respiratory phasicity. RESULTS: In all cases, atrial pulsatility and respiratory phasicity were present before and after catheter placement. There was no statistically significant change in the amount of spectral broadening after catheter placement. A mild increase in the peak blood flow velocity of 7 cm/sec (P = .04) in the ipsilateral brachiocephalic vein was demonstrated; however, no significant increase in velocity could be shown in the vein of insertion. CONCLUSION: In this clinical setting, the hemodynamic changes within the vein from the catheter placement are minimal. Any damping of the venous waveform seen with sonography performed to rule out upper extremity deep venous thrombosis secondary to indwelling catheter--for example, loss of atrial pulsatility or respiratory phasicity--is presumably due to the presence of venous thrombosis or stenosis. PMID- 8513215 TI - Traumatic aneurysm of the posterior circumflex humeral artery: a volleyball player's disease? PMID- 8513216 TI - Relationship of the inguinal ligament to pelvic radiographic landmarks: anatomic correlation and its role in femoral arteriography. AB - PURPOSE: Because of the known risks of suprainguinal catheterization, an anatomic study of the inguinal ligament was performed in 10 cadavers. MATERIALS AND METHODS: The position of the inguinal ligament as estimated by means of palpation and use of anatomic landmarks was compared with the actual ligament position as determined by means of groin dissection. Infrainguinal contrast material injections were also performed to assess competence of the inguinal ligament against spread of hematomas. RESULTS: The radiographically determined position was an average of 15.2 mm superior to the actual ligament position (range, 3 mm below to 24 mm above). The palpated position of the ligament was an average of 7.8 mm superior to its actual position (range, 7 mm below to 23 mm above). Contrast material injections demonstrated the inability of the inguinal ligament to contain blood or fluid, with formation of retroperitoneal hematomas. CONCLUSION: Puncture of the femoral vessels should be positioned in the midportion of the femoral head, as determined with fluoroscopy for maximum safety during catheterizations. PMID- 8513217 TI - Puncturing the pulseless femoral artery: a simple technique that uses palpation of anatomic landmarks. AB - PURPOSE: The authors report a simple technique in which palpation of anatomic landmarks is used to localize the pulseless common femoral artery. MATERIALS AND METHODS: A finger is placed immediately lateral to the pubic tubercle and inferior to the inguinal ligament to palpate the point allowing the most posterior depression. Anatomically, this depression lies between the iliopsoas muscle laterally and the pectineus muscle medially. The femoral vein lies in the floor of this depression, and 1.5 cm lateral to the depression lies the femoral artery. RESULTS: This anatomic relationship and its usefulness for locating the common femoral artery were verified by puncture and dissection of nine cadaveric groins and successful puncture of 19 pulseless arteries of 17 patients. CONCLUSION: The described technique was found to be quick, simple, and reliable and is now the authors' method of choice for puncturing the pulseless femoral artery. PMID- 8513218 TI - Prototype miniature endoluminal MR imaging catheter. AB - PURPOSE: The feasibility of a miniature endoluminal magnetic resonance (MR) detection coil was investigated for imaging mural and perimural anatomy of small, tubular structures. MATERIALS AND METHODS: To this end, remotely tunable, single loop, multiturn, receive-only radio-frequency coils, housed in 6-9-F arterial sheaths, were built. A 1.9-T imager was used. Phantom excitation was accomplished with a 62-mm-diameter bird-cage quadrature coil, and ex vivo specimen excitation was accomplished with a single-turn, untuned wire loop. Phantom images obtained with use of a 9-F catheter coil showed a signal-to-noise improvement on the border of 20 dB compared with images obtained with the quadrature coil. An 8-F catheter coil was used to obtain high-resolution (100 microns in-plane pixel size, 500 microns section thickness) spin-echo images (repetition time = 2,400 msec, echo time = 53 msec) of the wall of a fresh ex vivo human popliteal artery. RESULTS: Prospectively, these images were suggestive of the presence of diffuse intimal hyperplasia, medial calcification, and focal atherosclerotic plaque. These findings were confirmed histologically. Three-dimensional restacking of the axial images simplified examination of the normal layers and pathologic changes within the wall. The improved signal-to-noise characteristics of these miniature coils permit fast high-resolution imaging, allowing visualization of microscopic anatomic details. CONCLUSIONS: With further development, this technology may be useful for studying atherosclerosis and for providing imaging guidance during endoluminal MR interventions. PMID- 8513219 TI - Removal of a retroperitoneal foreign body by means of a percutaneous transrenal approach: case report. PMID- 8513220 TI - Guiding catheter for varicocele embolization. PMID- 8513221 TI - Placement of the Palmaz stent with use of an 8-F introducer sheath and Olbert balloons. AB - PURPOSE: The authors describe a modified technique for delivering Palmaz 30-mm stents. MATERIALS AND METHODS: The modification is based on the use of an 8-mm Olbert balloon mounted on a 5.8-F shaft. The Palmaz stent is crimped onto the balloon by using finger pressure only. An 8-F introducer sheath can be used instead of a 10-F sheath. The surface material of the balloon prevents the stent from moving as it is introduced through the sheath and lesion. The balloon has a very small profile after deflation, which means it can be easily removed without dislodging the stent. The balloon can be used for placement of more than one stent. RESULTS: Nineteen Palmaz 30-mm stents have been placed with this method, and there have been no complications or difficulties related to this method. In one case, four stents were delivered by using the same balloon. CONCLUSION: This modification should reduce the complications of stent delivery, especially in small iliofemoral systems. PMID- 8513222 TI - Balloon choice for metallic stent dilation. PMID- 8513223 TI - Recanalization of occluded intrahepatic portosystemic shunts: use of the Colapinto needle. PMID- 8513224 TI - The modern concept of association cortex. AB - Although enormous amounts of new neuroanatomical, neurophysiological and neurobehavioral data have been gathered on the association cortices in the past decade, it seems more permissible now than ever to use this functionally loaded concept. Its generality helps enormously, but the modern recognition of multiple interactive neural systems all contributing to cognition has diffused previous concerns relating to strict localization. PMID- 8513225 TI - The visual association cortex. AB - The concept of visual association cortex derives from early myelogenetic studies, assorted cases of so-called visual agnosia and much philosophical speculation. A review of the evidence suggests that it is perhaps time to review our concept of the visual association cortex. PMID- 8513226 TI - Frontal lobes. AB - The cortex of the frontal lobes is 'motor' cortex in the broadest sense of the word. It is the peak of a hierarchy of anterior neural structures dedicated to the execution of actions. For the temporal organization of movements, the frontal cortex has at its disposal two cognitive functions that complement each other: memory and motor set, i.e. the preparation for movement. Their operation is especially apparent at the highest stage of the frontal motor hierarchy, which is the prefrontal cortex. Recent microelectrode studies in behaving monkeys reveal that during retention of sensory information for subsequent action, memory and set are supported by two distinct but intermixed populations of prefrontal neurons. PMID- 8513227 TI - Memory and imagery in the temporal lobe. AB - Experimental and clinical studies in primates indicate that visual information is stored and retrieved by interactions between the temporal association area and the medial temporal lobe structures. Recent findings from single-neuron recordings have provided new evidence that perceptual aspects of the temporal neocortex are closely related to its memory function based on association. They further suggest that imagery is also implemented by the same neural mechanism that subserves memory retrieval. PMID- 8513228 TI - Coordinate transformations in the representation of spatial information. AB - Coordinate transformations are an essential aspect of behavior. They are required because sensory information is coded in the coordinates of the sensory epithelia (e.g. retina, skin) and must be transformed to the coordinates of muscles for movement. In this review we will concentrate on recent studies of visual-motor transformations. The studies show that representations of space are distributed, being specified in the activity of many cells rather than in the activity of individual cells. Furthermore, these distributed representations appear to be derived by a specific operation, which systematically combines visual signals with eye and head position signals. PMID- 8513229 TI - The perception of form and motion. AB - Although form and motion are two distinct aspects of visual processing, they do not start as separate entities in the visual system. Early analyses extract discontinuities in various image attributes and these can trace the outline of a form. When displaced, the same image features can give rise to impressions of motion. Recent work has overturned many of the assumptions about the contributions of different stimulus attributes to motion processing, and reorganized the classification of motion systems. The results have revealed unexpected interactions between attention and motion. Paralleling this research is work on the early stages of form learning and on the nature of the stored representations. PMID- 8513230 TI - Cerebral lateralization. AB - Recent findings suggest that cerebral laterality will not be understood in terms of simple dichotomies, such as the idea that the left hemisphere is analytic and the right holistic. Rather, hemisphere differences can be better explained in terms of relatively specific principles that extend over limited domains. For visual perception and mental imagery, the left hemisphere appears to be relatively better than the right at encoding component parts, representing visual categories, and encoding categorical spatial relations; in contrast, the right hemisphere appears to be relatively better at encoding overall patterns, representing specific instances, and encoding coordinate metric spatial relations. Recent neural network models support a hypothesis that ties together these disparate findings. PMID- 8513231 TI - Cortical plasticity and memory. AB - The roles of extrinsically modulated, plastic Hebb-like synapses and dynamic cortical cell assemblies underlying cortical plasticity in learning and memory operations are described. From our understanding of the distributed form of representation of learned behaviors in somatosensory and auditory cortical fields, and given new findings about the nature and distribution of responses representing learned and remembered stimuli in the inferior temporal cortex, a hypothetical picture of the cortical engram representing learned behaviors and memories is posited. PMID- 8513233 TI - Computational approaches to cognition: the bottom-up view. AB - How can higher level aspects of cognition, such as figure-ground segregation, object recognition, selective focal attention and ultimately even awareness, be implemented at the level of synapses and neurons? A number of theoretical studies emerging out of the connectionist and the computational neuroscience communities are starting to address these issues using neural plausible models. PMID- 8513232 TI - Neocortical long-term potentiation. AB - LTP is a form of activity-dependent synaptic plasticity that has been investigated mainly in the hippocampus. It is considered likely that similar mechanisms may also account for aspects of naturally occurring plasticity in the neocortex. Consequently, an increasing number of studies have been devoted to the investigation of neocortical LTP. Recent results suggest that at least two forms of LTP coexist in layer III of the neocortex. One depends on NMDA-receptor activation and resembles the LTP observed in hippocampal field CA1. A second form is independent of NMDA receptors and requires activation of voltage-sensitive Ca2+ channels. PMID- 8513234 TI - Computational approaches to cognition: top-down approaches. AB - Computational models are useful tools for exploring the nature of human cognitive processes. In particular, connectionist models are providing researchers with new ways of thinking about the basic nature of cognition and its implementation in the brain. They support novel explanations of important aspects of perception, memory, language, thought and cognitive development, and allow cognitive processes to be linked with the underlying physiological mechanisms. The models also aid our understanding of how disorders of brain function lead to disorders of cognition. PMID- 8513235 TI - Electrical and magnetic brain recordings: contributions to cognitive neuroscience. AB - Non-invasive recordings of electrical and magnetic fields from the human brain have revealed spatio-temporal patterns of neuronal activity associated with sensory, motor, and cognitive processes. Recent technical advances allow for improved localization of these activity patterns to specific brain structures. This review considers how electrical and magnetic recordings can help to delineate the neural systems and information processing operations that underlie auditory and visual perception, selective attention, mental chronometry, and memory. PMID- 8513236 TI - Cognitive aspects of classical conditioning. AB - Cognitive processes have been increasingly implicated in Pavlovian conditioning. Research in the past year has focused on questions of stimulus selection and the internal representation of events and the relations between them. Recent data support negative feedback models of selection that assume conditioning-dependent changes in processing of conditioned and unconditioned stimulus events, and suggest potential neural mechanisms that may underlie these processes. New models of conditioning propose a more detailed representation of individual conditioning episodes than traditionally assumed. The results of investigations into conditional discrimination learning imply a hierarchical organization of event representations, and illustrate the importance of conditioned modulatory processes as distinct from response elicitation. PMID- 8513237 TI - Neurology of developmental dyslexia. AB - Developmental dyslexia was until recently considered to belong solely in the domain of educational psychology. With the advent of better theories on language and reading, and better methods for assessing the structure and function of living human brains and for determining genetic transmission, dyslexia is now poised to become a focal concern of cognitive neuroscience, neurology, and genetic research. Still unresolved are questions relating to how much a reading disability represents a normal variation or a separate pathological entity, and whether the cognitive disorder is primarily cognitive, or secondary to a disorder in early perception. Recent findings from neuroanatomy, neurophysiology, neuropsychology, and genetics research are reviewed. (This review is an updated version of a review first published in Current Opinion In Neurology and Neurosurgery 1992, 5:71-76.) PMID- 8513238 TI - The biology and function of rapid eye movement sleep. AB - Rapid eye movement sleep, a stage of sleep that appears to be present in all marsupial and terrestrial placental mammals, was first identified in 1953. Although the brainstem mechanisms responsible for its generation have been clarified, the function of rapid eye movement sleep remains elusive. Recent findings suggest a role in memory processing. PMID- 8513239 TI - Cognitive neuroscience. PMID- 8513240 TI - Effects of collateral inhibition in a model of the immature rat cerebellar cortex: multineuron correlations. AB - A model of the immature rat cerebellar cortex is used to simulate the effect of the inhibitory recurrent collateral axons of the Purkinje cells on the spike trains in the network. Inhibition induces an important overall change in the statistical characteristics of individual spike trains. It is also instrumental in producing a strong cooperativity between the different neurons. Moreover, a functional spatial anisotropy appears. A specific entropy index is used to analyze levels of information transfer between clustered and faraway neurons in the network. The formatting effect of recurrent collateral inhibition on spike trains and on network functional dynamics is studied by means of a model of the newborn rat cerebellar cortex. This immature structure has simpler morphological characteristics and fewer physiological parameters than the adult one. It is thus a good candidate for the comparison between experimental and theoretical data. The model network is made of 256 formal neurons (FN), arranged in a square lattice. Each neuron is coupled to its eight nearest neighbors by inhibitory links. All the parameters of the different elements of the model--in particular integration of inhibitory and excitatory inputs--are given anatomical and physiological values derived from biological data. Activities of single FNs and correlations between spatially distant ones are analyzed with classical statistical techniques as well as with a specific informational entropy method we introduce. Simulation results indicate that inhibition is instrumental in: (1) the transformation of the spike train characteristics. This includes a lengthening of the mean interspike interval as well as an overall change in the statistical distribution of intervals, with an emergence of long-lasting ones; (2) the functional structuration of the network. Inhibitory connections between nearest neighbors induce a strong cooperativity between FNs. Furthermore a clear spatial anisotropy occurs in the functioning of the network, with inhibitory effects extending beyond local connectivity in preferential directions. We propose an interpretation of this functional structuration in terms of the various routes followed by the inhibition, including relay effects. The parameters of the model (levels of activities, inhibition rules and connectivities) were varied in order to test the robustness of the above results. Finally, the results are compared with those obtained in an experimental situation. PMID- 8513241 TI - Event-related potentials and repetition priming in young, middle-aged and elderly normal subjects. AB - Although the structure of semantic memory appears to be unaffected with increasing age, there is evidence that older adults are less efficient at accessing stored memory representations. Aging also results in a decline in the ability to use contextual information effectively, suggesting a deficit in episodic memory processes. The present experiment examines the effects of age on memory retrieval of stored representations and the use of contextual information. Event-related potentials (ERP) were recorded to immediate and delayed word repetition during a lexical decision task. Three groups of subjects were tested: young (mean = 27.3 years), middle (mean = 46.7 years) and old (mean = 67.4 years). Behavioral facilitation due to repetition did not significantly differ across groups. With increasing age, the ERP waveform showed a positive shift which began around 300-400 ms post-stimulus and was apparent across all stimulus types and response conditions. This positive shift may reflect an age-related decrease in cortical excitation. Although the onset of the ERP repetition effect was not affected by age, its duration for both immediate and delayed repetition was significantly prolonged. In the light of recent models of ERP word repetition effects, these results suggest that processes related to accessing stored representations in memory are unaffected by age. The extended duration of the repetition effect and the increase in the magnitude of the effect of delayed repetition with age suggest that aging affects processes related to the retrieval and use of contextual information in integrating a stimulus with its context. PMID- 8513242 TI - Phonological effects on the auditory N400 event-related brain potential. AB - We report 3 experiments exploring the responsiveness of the auditory N400 event related potential to the phonological relations between word or non-word targets and preceding prime words. When subjects had to decide whether primes and targets rhymed, non-rhyming words produced greater negativity in the N400 time range than rhyming words. The same effect was obtained when these targets were spoken by another voice than the prime words, suggesting that the effect is determined by phonological factors, and not merely by a physical-acoustic mismatch (Experiment 1). In the rhyming task, the differential N400 for non-rhyming vs. rhyming words was equally pronounced for non-rhyming vs. rhyming non-words (Experiment 2). In a lexical decision task on the same stimuli, a difference between non-rhyming and rhyming targets was obtained for words, but not for non-words (Experiment 3). The results show that the auditory N400 is sensitive to phonological variables. It is further proposed that phonological effects on the auditory N400 are not manifestations unique to phonological processes that demand conscious attention, but may also reflect operations that are performed automatically during auditory word recognition. PMID- 8513243 TI - Precision and accuracy of subjective time estimation in different memory disorders. AB - The aim of this study was to evaluate how different memory disorders affect subjective time durations. For this purpose we studied prospective time estimations in 4 amnesic (A) and in 15 Alzheimer's disease (AD) patients, and compared their performance with that of 5 matched young normal controls (YC) and 15 elderly subjects (EC). For the short-time durations we asked the subject to repeatedly reproduce a standard interval of 1 s. To test how subjects evaluated longer time durations, we choose a verbal estimation procedure. The subjects' task was to read either 5, 10, 20, or 40 digits appearing one at a time, while concurrently keeping the rhythm of 1 key press per second. At the end of each sequence, subjects had to judge the elapsed time from the beginning of the trial. Results showed that amnesics can correctly reproduce 1-s intervals. However, their accuracy of verbal estimates of longer durations was severely impaired. AD patients showed increased variability on repeated reproduction of 1-s intervals and were both inaccurate and imprecise in their verbal estimate of longer durations. Using the framework of the Scalar Timing Model, we conclude that amnesic patients exhibit a deficit in encoding and storing the current time for intervals that exceed their short-term memory range, while AD patients show a pattern of deficit that is explained by a more widespread involvement of both the clock, the memory, and the decisional mechanisms. PMID- 8513244 TI - Motor imagery activates the cerebellum regionally. A SPECT rCBF study with 99mTc HMPAO. AB - Our earlier findings of a cerebellar activation during motor imagery (Brain Res., 535 (1990) 313-317) were made with a technique with low regional resolution. Therefore we could not elucidate the distribution of the cerebellar activation. In the present study the cerebellar regional cerebral blood flow (rCBF) changes during motor imagery (MI) was measured with a single photon emission computed tomography (SPECT) rCBF method (99mTc-HMPAO) with higher regional resolution during (1) silent counting, and (2) MI (which included silent counting) in 17 normal subjects. Comparing the SPECT results from the two tasks revealed the regional activations during MI. We confirmed that the most pronounced regional activations during MI were found in the cerebellum, especially in its infero lateral parts on both sides. PMID- 8513245 TI - Evolution of a quality-based compensation model: the third generation. AB - U.S. Healthcare (USHC) contracts for care with primary care physicians who are compensated through capitation (i.e., a fixed payment at specific intervals per member for all care provided, irrespective of the number of services). The amount of capitation is dependent upon their quality assessment rating and their ability to manage the cost of care effectively. In January of 1992 USHC implemented its current, third-generation incentive model and significantly altered its Quality Care Compensation System. The evolution of this model is presented to demonstrate that this third-generation Quality Care Compensation Model is a fair and effective means of measuring and valuing the delivery of health care to a population. It rewards physicians who expend the extra effort to manage both quality and cost. The experience of USHC continues to demonstrate that it is possible to develop and monitor incentive mechanisms in a systematic fashion with quality improvement as the outcome. PMID- 8513246 TI - The administrative and clinical rationale for the total organization approach to continuous quality improvement. AB - In our view TQM and CQI represent important innovations in the continuing effort to develop higher performance organizations. Never before has the need been so great to improve quality while at the same time constraining, or reducing, costs. An increasing number of health care organizations can document their experiences that as quality goes up, costs can come down. The contribution of these new approaches is in some sense the wedding of many long established methodologies- the scientific method, statistical quality control, planning, joint problem solving, participative management, and empowerment of the work force. While this recognition could lend support to those who label this new model a fad, that perception denies the linkage of TQM/CQI to the greater stream of innovations pushing us toward ever-greater organizational excellence. Can we not take the philosophy and methods that are potentially useful and try them experimentally? Let our empirical tests tell us of their contribution. We believe the concepts and procedures of TQM/CQI will help us to be better in years to come, even though we highly respect our starting point. PMID- 8513247 TI - The continual improvement of health care. PMID- 8513248 TI - Quality in health care: whose responsibility is it? PMID- 8513249 TI - Primary care, quality improvement, and health systems change. AB - In this article, we have examined evidence that supports inferences regarding the critical role of primary care in determining the ultimate quality and success of our health care system as a whole. It seems clear that this nation has a critical need to correct the rapidly eroding structure and impact of our primary care system. We have suggested several strategies necessary to improve the United States primary care system. We need to correct the numeric imbalance of generalists to specialists by enhancing motivation to enter this career field. To enhance primary care as a career choice, we must increase the status, contribution, and rewards of primary practitioners. Finally, to facilitate future growth and success, we must enhance the scholarly base of knowledge in this field, particularly as related to quality improvement technology and managed health care. PMID- 8513250 TI - Total quality improvement: a study of Veterans Affairs Medical Center directors and QA coordinators. AB - A national survey of all Veterans Affairs Medical Centers' (N = 167) directors and Quality Assurance (QA) coordinators was conducted. The survey solicited feedback of respondents' attitudes and perceptions toward the implementation of Total Quality Improvement (TQI) in their facilities. A Likert scale type of responses was collected and further analyzed to measure the degree of agreement or disagreement of the respondents to the survey statements. The following sections were proposed: (a) attitudes and perceptions; (b) rankings; and (c) demographics of respondents and their facilities. The results of the survey indicate an overwhelming agreement on the implementation methodologies, impact on other programs, objectives, and philosophies of TQI. Both the directors and QA coordinators responded positively on the future of TQI in health care. PMID- 8513251 TI - Unnecessary emergency transport and care of grand mal seizures. AB - Every source quoted in this study has clearly refuted the need for emergency transport and care of an uncomplicated grand mal seizure in a managed epileptic patient. This review of a large patient population has determined that 27% of emergency department seizures were uncomplicated and occurred in patients already under care. This represented 0.25% of all emergency department visits and nearly $200,000 in claims to this managed care entity per year. Taking some statistical liberties, a national health care expenditure of $270,000,000 is suggested for this single abuse. It is hoped that further education of the public, medical community, and epileptic patients will produce a comfort level that permits decisions about emergency transport and care of seizures. These savings could translate into basic health insurance for thousands of our medically deprived citizens. PMID- 8513253 TI - Can networked hospital performance comparisons be linked with total quality management? A scenario based on the Pennsylvania Health Care Cost Containment Council. AB - The Pennsylvania Health Care Cost Containment Council publishes annually performance comparisons on hospitals in nine regions of the state. As a result, hospitals are under public pressure to use these data in Total Quality Management programs. This article illustrates both the opportunity and the risk that publicly funded information poses for hospitals. PMID- 8513252 TI - Clinical quality improvement in a multihospital system: the voluntary hospitals of America/Pennsylvania experience. AB - Sharing of patient outcome data among hospitals hastened the evolution of continuous quality improvement at Voluntary Hospitals of American/Pennsylvania (VHA/PA) to a focus on learning from the best: clinical benchmarking. Analysis of VHA/PA MedisGroups comparative outcome data showed significant variation. In the first study, variations from 3 to 25% normal appendectomy rates were noted. A second study on primary and secondary cesarean section rates again showed variation in outcomes. A study of the benchmark hospitals showed characteristics, specific to those institutions, that resulted in excellent outcomes. To quantify best processes, VHA/PA has embarked on a clinical benchmarking project with the assistance of MediQual Systems, Inc. PMID- 8513254 TI - The walk-through patient-focus assessment: preliminary results in augmenting patient satisfaction data. AB - This article describes a new tool, the Walk-through Patient-focus Assessment Tool (WTPFAT), which is intended to supplement traditional methods of collecting patient satisfaction data. The WTPFAT is an instrument that has been developed for use by health care workers, managers, and professionals to examine their environment from a patient-focus point of view. PMID- 8513255 TI - The use of standardized indicators as quality improvement tools: an application in Pennsylvania nursing homes. AB - The Institute of Medicine recommends the use of key quality indicators (resident outcomes that suggest the presence of good or bad care) as tools for interfacility comparison of the quality of care provided in nursing homes. In the spirit of this recommendation, the Health Care Financing Administration released selected results from its Medicare and Medicaid Annual Certification Survey to guide consumers in purchasing nursing home services. However, because this information is published without adjustment for resident characteristics that can influence the outcomes of nursing home care, its utility for policy-makers or consumers interested in variation in nursing home quality is limited. This research study utilizes federal and state survey data to evaluate variations in mortality, pressure ulcers, urethral catheterization, and physical restraint use in 438 Medicare-certified skilled nursing care facilities in Pennsylvania. A standardization function adjusting for resident characteristics known to influence outcomes is developed and estimated by ordinary least squares regression. Results suggest considerable variation in rates for these indicators across Pennsylvania nursing home facilities. Alternative uses for risk-adjusted key quality indicators as tools for improving nursing home quality and assisting potential consumers of nursing home care in making better informed choices are considered. PMID- 8513256 TI - Using total quality management in long-term care case management. AB - Long-term care (LTC) case management has emerged as a way of addressing problems in the long term care system. Case managers serve as links between chronically ill and disabled individuals and the services these individuals need but of which they often are unaware. In this capacity, case managers address the fragmentation in the long-term care system. In guiding clients to cost-effective ways of meeting their long-term care needs, case managers also address the need for cost containment in long-term care. To ensure that case management is effectively addressing these and other problems, attention to quality is essential. However, quality assurance programs too often focus on minutiae rather than on true indicators of quality. In addition, people who are not involved in the related areas frequently make decisions about quality. These decisions impose additional, and sometimes unnecessary, restrictions on the people who are required to implement them. Total quality management (TQM) offers a new approach. In this article, a proposal is made to incorporate TQM principles into LTC case management. The LTC case management demonstration project currently underway in Virginia serves as the case study for this proposal. The proposal demonstrates a process in which quality can be built into a case management system in a way that involves the people who will implement the resultant changes. The proposal shows how case management staff members can learn to identify areas where quality is impaired and to use techniques to aid them in identifying the causes of problems. A procedure for testing solutions and for incorporating the findings into the project is described. PMID- 8513257 TI - Design and implementation of the quality improvement process at a community teaching hospital. PMID- 8513258 TI - Application of the FOCUS-PDCA model to home care equipment management. AB - Issuing durable medical equipment to patients for use at home is a costly and complex process. Selection, delivery, setup, and maintenance of home care equipment and the education of patients in its use are currently included in Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) accreditation surveys for those health care organizations that issue equipment. In this Department of Veterans Affairs teaching hospital, the process was complicated by eligibility regulations and frequently rotating housestaff. We organized a team who studied the process and identified opportunities for improvement in three areas: the selection of equipment items ordered, management of equipment-related data, and standardization of equipment delivery contracts. We produced a reference manual for staff, developed a simple database, and incorporated JCAHO home care equipment management standards into equipment delivery vendor contracts. The results of the team's efforts were an increase in efficiency, a decrease in discharge delays, and improved continuity of care. We chose to use the FOCUS-PDCA model to illustrate our approach to improving these processes. PMID- 8513259 TI - The role of governing boards of trustees in promoting total quality management. AB - As total quality management becomes more accepted in health care organizations, it is apparent that organization-wide efforts will be needed to reinforce and institutionalize these changes. This article stresses the importance of the direct involvement of the board of trustees in setting the climate for successful interventions. The board must be open to using its influence on the system to facilitate changes. In addition, the board must be a part of the total quality management process. This article concludes with 10 guidelines for the implementation of TQM, each designed to help ensure positive outcomes. PMID- 8513260 TI - Breast cancer: diagnosis and treatment. AB - Advanced breast cancer is a complicated disease. To adequately treat it, the physician must fully stage the patient. Treatment options are determined by the amount of disease and the type of breast cancer. These include hormonal therapy, chemotherapy, surgical therapy, and radiotherapy. At times some or all of these are used either in combination or sequentially. Newer experimental therapies are promising. Even so, once the disease has spread beyond the breast and regional lymph nodes, it is not generally curable. Emphasis on early detection is justified for this reason. PMID- 8513261 TI - The management of the psychosocial impact of breast cancer. AB - Breast cancer patients often experience severe psychological and physical distress that challenges their self-esteem. And yet, from a seemingly uncontrollable, frightening, and life-threatening set of circumstances, women can emerge with their self-esteem, though often rearranged and changed, intact and restored. By providing information, resources, and support, NPs can help a breast cancer patient make deposits to her self-esteem accounts: her interpersonal relationships, her body image, her achievements, and her identity, thereby enabling her to manage her illness more effectively. PMID- 8513262 TI - The role of the comprehensive breast center. AB - Continuous progress in breast health and breast cancer care has been made over the past few decades. Major advances include the widespread use of screening mammography, resulting in mortality reduction; the evolution of multimodality treatment planning, resulting in more coordinated care; and the use of adjuvant chemotherapy, resulting in prolonged survival. In addition, the emergence of a new consumerism has resulted in more research funding, political activism, and legislative mandates in many states for screening mammography reimbursement and informed consent laws. The development of comprehensive breast centers represents another measure of success in the area of health care delivery, which has traditionally been fragmented. This article will describe the role of the NP in relation to a comprehensive breast center, as well as how the NP can improve the provision of primary breast care, identify quality in potential consultants, and effectively collaborate and communicate with other members of the health care team, including the patient and family. PMID- 8513263 TI - Deja vu all over again? PMID- 8513264 TI - Eve Cook Hoygaard: breast center coordinator and nurse practitioner. Interview by Irene Sullivan and Karna Bramble. PMID- 8513265 TI - Analysis of a breast cancer lawsuit. PMID- 8513266 TI - Tamoxifen. PMID- 8513267 TI - Improving the effectiveness of breast self-examination in the early detection of breast cancer: a selective review of the literature. AB - This paper selectively reviews the literature on breast self-examination. The evidence for the use of silicone models to teach lump detection skill and for individual instruction is evaluated, and recommendations are made for the NP's role in teaching breast self-examination. PMID- 8513268 TI - Achieving competence in clinical breast examination. AB - Literature documenting the breadth and quality of prevalent clinical breast examination (CBE) practice is briefly reviewed. A more thorough procedure, emphasizing training in tactile discrimination, is described and illustrated. PMID- 8513269 TI - Breast cancer risk: the role of the nurse practitioner. AB - Information about breast cancer risk is confusing to many patients. This paper focuses on some of the more important risk factors for breast cancer: age, benign breast disease, diet, hormone replacement therapy at menopause, and family and reproductive history. Some of the social factors that can influence receptivity to risk information are briefly mentioned. With their experience in educating patients and families, NPs are ideally suited to provide information about breast cancer risk. PMID- 8513270 TI - Benign breast disease. AB - Benign breast disease is common with an estimate of over half the female population at sometime seeking medical attention for a breast problem. The clinician must prove that the woman with a breast problem (ie, tenderness, lump, discharge) does not have a malignancy. This is done using a history and physical examination and, when indicated, mammography, ultrasonography, ductography, fine needle aspiration biopsy, or excisional biopsy. A comprehensive breast center allows for an efficient and cost-effective workup for women with a breast problem. In this context, benign breast disease and preinvasive breast cancer is presented. PMID- 8513271 TI - Generation of senescent cell antigen on old cells initiates IgG binding to a neoantigen. AB - An aging antigen, senescent cell antigen, resides on the 911 amino acid membrane protein band 3. It marks cells for removal by initiating specific IgG autoantibody binding. Band 3 is a ubiquitous membrane transport protein found in the plasma membrane of diverse cell types and tissues, and in nuclear, mitochondrial and Golgi membranes. Band 3 in tissues such as brain performs the same functions as it does in red cells. Senescent cell antigen is generated on brain membranes. Oxidation is a mechanism for generating senescent cell antigen. Neither cross-linking nor hemoglobin appear to play a role in generating senescent cell antigen. Although storage is the only in vitro model that mimics cellular aging in situ, we have discovered three alterations/mutations of band 3 that permit insight into aging in situ. One mutation with an addition to band 3 has normal or decelerated red cell aging. In contrast, another band 3 alteration with a suspected deletion or substitution that renders band 3 more susceptible to proteolysis, shows accelerated aging. The third alteration which is also more susceptible to proteolysis is associated with neurologic defects. Peptide technology was used to map the aging antigenic sites and anion transport sites on band 3 using a competitive inhibition assay and immunoblotting with IgG directed against the aging antigen on old cells. Results indicate that: a) aging antigenic sites reside on human band 3 residues 538-554, and 812-830; b) a putative ankyrin binding region peptide is not involved in senescent cell antigen activity and c) carbohydrate moieties are not required for the antigenicity or recognition of senescent cell antigen since synthetic peptides alone abolish binding of senescent cell IgG to erythrocytes. Peptide residues 588-594 (a 7 amino acid peptide), 822-839 and 869-883 were the most active inhibitors of anion transport (P < or = 0.001 compared to control without peptide). Localization of the active antigenic and transport sites on band 3 molecule facilitates the definition of molecular changes occurring during aging that initiate molecular as well as cellular degeneration. The role of senescent cell antigen and band 3 in brain aging and Alzheimer's disease is discussed. PMID- 8513272 TI - A quantitative assessment of non specific pinocytosis by human endothelial cells surviving in vitro. AB - Human umbilical vein endothelial cells have been assayed in vitro, 24 hrs. after plating, for non specific pinocytic activity. The culture conditions were designed to minimize the exogenous stimulations of pinocytosis, such as those possibly coming from mitotic induction and chemical and contact-dependent signaling. Two different markers were used: Lucifer Yellow CH (LY), and three different preparations of horseradish peroxidase, a multiple form (type II) composed of five different isoenzymes, and two purified acidic (type VIII) and basic (type IX) isoenzymes. The uptake of LY appears to depend on both fluid phase incorporation and non specific adsorption to the cell surface, and it shows a linear monophasic dependence on time and a linear diphasic dependence on concentration. This probe is actively chased from the cells to an extent proportional to the amount incorporated. Therefore, the endocytic index obtained from the LY incorporation data is not a reliable estimate of extracellular fluid incorporation. The three different forms of HRP share an incorporation pattern linearly dependent on both time and concentration, consistent with the classical interpretation of a simple fluid-phase mechanism of intracellular uptake; however, the rates of uptake and chase activity of the pure isoenzymes are clearly different from that of the multiple form. The observed differences are related to possible local variations in the physicochemical properties of the cell surface, which may restrict the cell surface area suitable for fluid-phase uptake of differently charged macromolecular probes. PMID- 8513273 TI - Fluorescence studies on the binding of a chemotactic peptide to human spermatozoa. AB - The binding of N-Formyl-Met-Leu-Phe-Lys-Dansyl, fluorescent analog of the chemotactic peptide, Formyl-Met-Leu-Phe, to human ejaculated spermatozoa and to isolated heads and tails of spermatozoa was studied by fluorescence microscopy and spectrofluorimetry. The results indicate that the peptide binds to the surface of human spermatozoa and to isolated heads and tails of spermatozoa. The binding was not inhibited by BSA, human seminal plasma and Boc-Met-Leu-Phe-Lys but Formyl-Met-Leu-Phe-Lys reduced significantly the binding of the peptide. Evidence is also provided to indicate that the peptide binds with a higher affinity in the tail region of the spermatozoa. PMID- 8513274 TI - NMR study of seed hydration: effect of pH and ionic strength on water uptake of soaked cowpeas. AB - A NMR method based on the analysis of the transverse magnetization decay curve of water protons, was employed to study the hydration process of Ife Brown cowpeas. In order to investigate the role of pH and Ionic Strength (IS) on the hydration process the beans were soaked in solutions at different IS and at different pH constant IS. The kinetic constant for the hydration process and the water-holding capacity of the seeds in different conditions were measured. PMID- 8513275 TI - NMR investigation of the dynamic behaviour of guar galactomannan water solutions. AB - Proton longitudinal and transverse relaxation times have been measured to examine the concentration dependence of the dynamic behaviour of guar galactomannan aqueous solutions. Two concentration regimes have been evidenced from our results, with a limiting concentration separating the two regimens at about 3% guar concentration. The T1/T2 ratio indicates that even bulk water experiences anisotropic motions over the limiting concentration. A comparison is made with T1/T2 ratios evaluated in glucose solutions which do not exhibit any deviation from isotropic behaviour of bulk water molecules. The results are discussed taking into account topological entanglement interactions between polysaccharide molecules, according to the current model for the solution behaviour of guar galactomannan. PMID- 8513276 TI - Ameliorative capacities of vitamins and monothiols administered alone or in combinations in methylmercury mobilisation in nervous and non-nervous tissues of mice. AB - The extent of mercury mobilisation was recorded from various tissues (brain, spinal cord, liver and kidney) of male mice administered with a daily dose of methylmercury chloride (1 mg/kg) for seven days. For this purpose 10 groups of animals were intoxicated. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. To the rest of the groups were given a daily dose of N-acetyl-DL homocysteine thiolactone (NAHT), glutathione (GSH), vitamin B Complex and E, applied either alone or in combinations. All these animals were sacrificed on the 15th day. The mercury clearance rate during thiols, vitamins and their co administration was examined. Study shows that both the vitamins were able to increase mercury elimination from the nervous and non-nervous tissues. Their combination with NAHT was not suitable as mercury level was increased in all the tissues except kidney as compared to NAHT alone treated group. However, vitamin B Complex combination with glutathione was much advantageous. It is concluded from the overall study that application of vitamin B Complex and E either alone or in combination with GSH is quite suitable for methylmercury post-therapy. PMID- 8513277 TI - Alterations of retinoblastoma susceptible gene accompanied by c-myc amplification in human bone and soft tissue tumors. AB - The present study was undertaken to examine oncogene abnormalities in human bone and soft tissue tumors. Twenty four tumor tissues and one human cell strain established from an osteosarcoma were examined by Southern blot analysis using a recessive oncogene (p0.9R and p3.8R derived from a cDNA of the Rb gene) and eight dominant oncogenes (c-myc, c-K-ras, c-fos, c-raf-1, c-fms, c-sis, N-myc, and c erb B) as probes. Homozygous deletions or other alterations within the Rb locus were found in 3 of 6 osteosarcomas, 1 osteosarcoma cell line, 1 of 3 malignant fibrous histiocytomas and 1 of 2 Ewing's sarcomas. On the other hand, amplification of c-myc was found in 2 osteosarcomas and 1 osteosarcoma cell line. All cases with c-myc amplification had alterations in the structure of the Rb locus, and these patients showed rapid clinical malignancy progression and a probable tendency to bone metastases. Results of this study suggest that structural alterations of the Rb gene and amplification of c-myc might play an important role in the clinical course and pathogenesis of osteosarcoma. PMID- 8513278 TI - Release of cholecystokinin in the central nervous system. AB - The octapeptide cholecystokinin (CCK) is one of the most abundant neuropeptides of the central nervous system. A number of features (for instance heterogeneity of the regional distribution, subcellular localization at the nerve terminal level, calcium-dependent release upon nervous tissue depolarization) support the candidacy of CCK as a neurotransmitter. The reported co-existence of CCK and dopamine in some meso-limbic neurons has led to speculation that the neuropeptide may interact with the catecholamine in neuropsychopathologies linked to dopamine dysfunctions, like schizophrenia. Data from the experimental animals have so far generated conflicting results. It should be noted that the interactions between CCK and dopamine, and, in particular, the effects of CCK and dopamine on each other release, both in vitro and in vivo, have been poorly investigated and would require special attention. Evidence is accumulating that CCK may participate in the expression of anxiety. Indeed antagonists at the central CCK receptors exhibit anxiolytic activity in the laboratory animal. An interesting linkage appears to exist in the brain between 5-hydroxytryptamine (5-HT) and CCK. Activation of 5-HT3 receptors was found to increase CCK release from rat cortical or nucleus accumbens synaptosomes. Interestingly, antagonists at 5-HT3 receptors appear to possess anxiolytic activity. Recent studies carried out in conscious unrestrained rats show that the calcium-dependent, tetrodotoxin-sensitive release of CCK-like immunoreactivity evoked in the rat frontal cortex by veratrine infusion can be inhibited by submicromolar concentrations of 5-HT3 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513279 TI - Cholecystokinin release in the central nervous system. PMID- 8513280 TI - Ageing and monoamine turnover in the lateral geniculate nucleus and visual cortex of the rat. AB - The effects of ageing on the turnover of dopamine, noradrenaline and serotonin in the lateral geniculate nucleus and the visual cortex were evaluated, using high performance liquid chromatography (HPLC) with electrochemical detection. Compared to adult animals, aged rats showed more changes in the visual cortex than in the lateral geniculate nucleus, with dopamine turnover decreased in both structures and noradrenaline turnover unaltered. Changes in serotonin turnover were witnessed only in the visual cortex. A decrease in the monoamine oxidase-A to -B ratio was also observed with increased age for both the lateral geniculate nucleus and visual cortex. PMID- 8513281 TI - Nucleotide sequence of rat calretinin cDNA. AB - A rat calretinin cDNA clone was selected by antibody screening of a lambda gt11 brain library. The sequence revealed remarkable nucleotide and amino acid homology with human calretinin (91.1% and 98.5%, respectively), with only four amino acid differences. A high degree of homology with chick calretinin was also observed (79.8% and 86.6%, respectively), with 36 amino acid differences. Although the role of this central nervous system protein has not been well characterized, the evolutionarily conserved calcium binding domains and connecting regions, in addition to the limited local changes observed between rat and chick primary structure, lead us to believe that calretinin interacts with other highly conserved constituents of brain cells. This calretinin cDNA clone provides a new probe for the analysis of a specific subset of neurons in the central nervous system. The probe will allow a more detailed analysis of calretinin regulation in the brain and will be useful for screening genomic libraries for the complete chromosomal gene. (GenBank accession No X66974). PMID- 8513282 TI - Effects of detergents on binding of 5-hydroxytryptamine3 receptor antagonist [3H]GR65630 to rat cortical membranes. AB - In the absence of detergent, specific binding of [3H]GR65630, a 5 hydroxytryptamine3 (5-HT3) antagonist, determined in the presence of 5-HT3 receptor antagonist ICS205-930, was at most 30% of the total binding. To decrease the level of nonspecific binding, the effects of detergents on [3H]GR65630 binding to rat cortical membranes were investigated. The use of a detergent (0.1% Lubrol PX or Triton X-100) decreased nonspecific binding, increasing the proportion of specific binding to 70% of total binding. In the presence of 0.1% Triton X-100, binding of [3H]GR65630 was rapid, reversible and saturable at 25 degrees C. The rank order of 5-HT3 receptor active drugs in inhibiting [3H]GR65630 binding was quipazine > ICS205-930 > 2-methyl-5-HT = 5-HT > metoclopramide, which confirmed that [3H]GR65630 efficiently labeled 5-HT3 receptors in the presence of Triton X-100. Triton X-100 improved 5-HT3 receptor binding with rat brain membranes. PMID- 8513283 TI - Variability in brain ganglioside content and composition of endothermic mammals, heterothermic hibernators and ectothermic fishes. AB - Content and composition of brain gangliosides were compared among endothermic mammals, heterothermic hibernators and ectothermic fishes from habitats with extreme ambient temperatures (tropic vs. antarctic waters). In general the content of brain gangliosides in fishes is significantly lower and exhibits a greater variability than in mammals. The composition of brain gangliosides was investigated using both one- and two-dimensional High Performance Thin Layer Chromatography (HPTLC). Both techniques showed a remarkable increase in the number of individual ganglioside fractions and an additional increase of higher polar fractions in fishes as compared with mammals. The 2D-HPTLC revealed a significant decrease in the relative proportion of alkali-labile gangliosides in the course of evolution from fish to mammals. Moreover this decrease in alkali lability is correlated with the state of thermal adaptation (antarctic fishes, 53 66%; tropical cichlid fish, 35%). These results provide additional evidence for the notion that the extremely high polarity of brain gangliosides, especially of cold-blooded vertebrates, reflects a very efficient mechanism on the molecular level to keep the neuronal membrane functional under low temperature conditions. PMID- 8513284 TI - Platelet-activating factor and its methoxy-analogue ET-18-OCH3 stimulate immediate early gene expression in rat astroglial cultures. AB - In the present paper we analyzed c-fos and zif/268 expression in rat primary astroglial cell cultures after treatment with Platelet-activating Factor (PAF) and its 2-O-methyl-analogue, 1-O-octadecyl-2-O-methoxy-glycero-3-phosphocholine (ET-18-OCH3). Both compounds, at a dose (2 microM) that did not produce toxic effects on astroglial cells, induced a rapid and transient increase of c-fos and zif/268 mRNA level. Pretreatment of astroglial cells with the PAF antagonist BN50730 (5 microM) 10 min prior to the addition of alkyl-phospholipids almost completely prevented the activation of the immediate early genes. On the contrary triazolam, another PAF inhibitor, did not block PAF induced gene expression when added to the medium at 5 microM concentration. ET-18-OCH3 effect on gene expression is blocked by the same antagonist (BN50730) which is effective in inhibiting PAF effect on astrocytes, suggesting that both substances act through the same binding site. Results obtained support the view that astroglial cells are a cellular target for this lipid mediator, and, like macrophages, respond to its methoxy-analogue. PMID- 8513285 TI - Ethanol and protein kinase C in rat brain. AB - The effect of chronic ethanol consumption on the catalytic activity of protein kinase C isolated from rat brain was studied in two different ways. Enzyme activity was first measured by phosphorylation of Histone IIIS in vitro. There was no change in the activity of the cytosolic enzyme. Membrane-associated enzyme activity was reduced in the ethanol-treated animal. This difference was not evident if the enzyme was stimulated by arachidonate. The reduction in enzyme activity was confirmed by analysis of the phosphorylation of endogenous substrates in intact synaptosomes. When the binding of the ligand [3H]phorbol dibutyrate was measured by quantitative autoradiography, increased binding to membrane-associated protein kinase C was observed in the CA1 region of the hippocampus but not in other brain regions. These results indicate that ethanol treatment results in a general reduction in membrane-associated protein kinase C activity as measured in vitro but the effect may not be consistent in all brain regions. The differential effect in the CA1 region of the hippocampus may be a reflection of a disruption in the normal regulation of protein kinase C activity in this area and may indicate that this region is a sensitive target for the action of ethanol. PMID- 8513286 TI - Identification of vasoactive intestinal polypeptide (VIP) binding protein in bovine pineal gland. AB - Vasoactive intestinal polypeptide (VIP) containing nerves are present in close proximity to epithelial, endocrine, and vascular smooth muscle cells. The pineal gland, known also as a "neuroendocrine transducer organ" contains a high content of VIP which prompted us to characterize the binding sites for VIP in this organ. [Tyr10-125I]VIP was bound selectively and specifically to pineal membrane preparations in a time-dependent fashion. Scatchard analysis demonstrated a single class of high affinity binding sites with a dissociation constant (Kd) value of 5.7 +/- 0.52 nmol/1 and a receptor density (Bmax) value of 440 +/- 35 fmol/mg protein. A Hill Plot with a slope of 1.013 indicated the absence of cooperativity. Covalent crosslinking with [Tyr10-125I]VIP followed by SDS electrophoresis and autoradiography, revealed that the VIP binding protein exhibited a molecular weight of 51.8 +/- 0.5 kDa. The precise function of pineal VIP binding protein remains to be delineated. PMID- 8513287 TI - Aerobic exercise in pregnancy: an update. AB - The endocrine effects of pregnancy cause striking changes in maternal metabolism, cardiovascular regulation, acid-base balance, and thermoregulation at rest and during standard submaximal exercise. The apparent purpose of these changes is to accommodate fetal needs in addition to those of the exercising woman. A significant body of evidence supports the hypothesis that healthy women can perform acute exercise of moderate intensity and duration without jeopardizing fetal well-being. Compiled studies also suggest that maximal oxygen uptake (VO2max, L.min-1) and the work rate at the onset of blood lactate accumulation (OBLA) are not significantly altered during the course of a normal pregnancy. However, some evidence suggests that maximal anaerobic power may be reduced. More information is needed on maternal cardiorespiratory function, carbohydrate metabolism, and acid-base balance at exercise intensities above OBLA and on fetal adaptability to strenuous maternal exercise. Recent studies support the view that moderate fitness conditioning can augment maternal metabolic and cardiopulmonary capacities without altering fetal development or pregnancy outcome. Implications of recent scientific studies for the design of aerobic exercise programs for pregnant women are discussed. PMID- 8513288 TI - Heart rate/stroke volume relationship during upright exercise in long-term diabetics. AB - The changes in stroke volume (SV) during upright exercise were studied in 20 insulin-dependent diabetics (IDDM) and 20 age- and sex-matched controls. None of the diabetics had any cardiovascular symptoms. In addition, tests of autonomic function were conducted in the diabetics, assessing changes in heart rate (HR) during deep breathing and the Valsalva maneuver. During exercise the SV in the controls gradually increased and then remained essentially unchanged until maximum HR was achieved. Seven of the diabetics failed to sustain an initial increase in SV (fall > 15%), eight showed a "delayed" increase in SV, and the remaining five demonstrated an increasing SV over the range from rest to peak exercise. Abnormal autonomic function results were found during deep breathing (four diabetics) and the Valsalva maneuver (four diabetics). Findings indicate that cardiac function could be abnormal in IDDM without evidence of autonomic dysfunction. This abnormality could be due to a specific cardiomyopathy. PMID- 8513289 TI - [Maximal physiological response during exertion in quadriplegic subjects]. AB - Devices used for the assessment of physical working capacity in quadriplegics may be determinant in terms of efficiency during maximal exercise testing. The aim of this study was to compare the physiological responses of a group of quadriplegics during graded exercise tests on arm cranking ergometer (ACE) and wheelchair ergometer (WE). Fifty subjects, age 34.1 (+/- 9.5) years, participated in the study. Measurements comprised heart rate, ventilation, oxygen consumption, and power output. Unlike other studies suggesting a higher physical working capacity on ACE compared with WE, no significant differences were observed in physiological measurements between the two ergometers. However, power output on ACE was 65% higher than that of WE (p < or = 0.001). These results suggest that power output of quadriplegics on ACE is higher due to differences in mechanical patterns required to induce movements of propelling (arm cranking vs. rolling movements). The need to link the assessment results to the type of locomotion used by the spinal cord injured persons may suggest the use of WE for testing and training in such individuals. PMID- 8513290 TI - Prediction of maximal oxygen uptake from a modified Canadian aerobic fitness test. AB - The purpose of the present study was to increase the accuracy of prediction of VO2max from the Canadian Aerobic Fitness Test (CAFT) by modifying the protocol and developing a new equation. Males and females between the ages of 15 and 69 years (n = 129) were tested on four occasions. Each subject performed four submaximal step tests (modified CAFT protocol) and a maximal treadmill test. The modification of the protocol consisted of allowing each subject to complete the number of stages needed to reach a target heart rate of 85% of age-predicted maximum. This required adding a new Stage 8 for men and Stages 7 and 8 for women. The prediction equation resulting from regression analysis was, VO2max (ml.kg-1 x min-1) = 32.0 + 16.0 VO2 - 0.24 Age - 0.17 Wt (R2 - 0.77; delta 2 - 26.6), where VO2 = oxygen cost of stepping at the final level (L.min-1), Age = age (yrs), and Wt = body mass (kg). PMID- 8513291 TI - Muscle ultrastructure after strength training with placebo or anabolic steroid. AB - The influence of strength training on muscle fiber area, capillary ultrastructure, and capillary supply was studied in experienced male bodybuilders taking either anabolic steroids or a placebo. During 8 weeks, 13 subjects received a weekly injection of either placebo or nandrolone decanoate (starting dose 200 mg, followed by 100 mg weekly), in a double-blind, counterbalanced design. Before and after 8 weeks a needle biopsy was taken from the vastus lateralis muscle for studying morphometric characteristics of fibers and ultrastructure and morphometric characteristics of capillaries. The fiber cross sectional area increased significantly only after steroid treatment. Capillary ultrastructure and capillary supply were not changed after the training period. In none of the measured parameters was any difference found between placebo and steroid treatment. PMID- 8513292 TI - Validity and reliability of the Cosmed K2 to measure oxygen uptake. AB - The validity and reliability of the Cosmed K2 was tested in comparison with a Quinton on-line oxygen analysing system. A female subject was monitored on a treadmill using a progressive protocol and was measured on three occasions with each system. It was found at low workloads that the Cosmed K2 and the Quinton gave the same measure of oxygen uptake; at higher workloads the Cosmed K2 gave lower values, and at peak oxygen uptake the Cosmed K2 measured 22.2% less than the Quinton. The difference in the measurement of VE at peak oxygen uptake was 13%. The Cosmed K2's measurement of VO2 showed a greater variability between trials (variation coefficient 3.0-11.4%) than the Quinton (variation coefficient 1.1-3.9%). PMID- 8513293 TI - The calibration of a sit-ups task using the Rasch Poisson Counts model. AB - The purpose of this study was to calibrate a nationally used sit-ups test using the Rasch Poisson Counts model and evaluate the model-data fit. The total number of subjects was 8,723, consisting of 4,486 girls and 4,237 boys, ages 10 to 18. The estimated difficulty of the sit-ups task was -2.80, which was appropriate for a majority of examinees whose ability levels ranged from .09 to 1.39. After the calibration, boys and girls as well as different age groups were compared under the same metric. Graphs of the model-data fit demonstrated that the model-data fit at a low ability level was not as good as the fit at a high ability, which could be caused by violation of assumptions of the model that examinees have the same performance speed throughout the test and that the speed at a given time is independent of the number of sit-ups completed so far. PMID- 8513294 TI - The ERE-like sequence from the promoter region of the testis specific hsp70 related gene is not estrogen responsive. AB - The 5'flanking region of the hsp70-related gene which is specifically expressed in rat and mouse spermatocytes contains the GGTCAnnnCGACC sequence closely resembling the palindromic consensus ERE (estrogen responsive element, GGTCAnnnTGACC). We used a transient expression assay to study whether this ERE like sequence can transfer estrogen responsiveness either to heterologous or homologous promoters linked to a reporter CAT gene. We found that the GGTCAnnnCGACC sequence either as an isolated element or in its natural sequence context does not respond to hormone stimulation in MCF-7 and Fe33 cells. This observation points to the importance of the T-nucleotide in a right half palindrome of ERE for ligand-dependent activation of transcription. PMID- 8513295 TI - Initiation of DNA synthesis in a high molecular weight fraction of Xenopus egg extract. AB - Xenopus egg extract was fractionated by gel-filtration column chromatography and DNA synthetic activity was examined using double-stranded DNA as a template. The major activity eluted had an apparent molecular mass of about 300 kDa. Product analyses showed that de novo DNA synthesis occurs with formation of replication bubbles, thereby suggesting that this fraction catalyzes the initiation of DNA replication. Activities of DNA polymerase alpha-primase and DNA helicase overlapped with the DNA synthetic activity, but the elution profiles of the enzymes differed from that of the DNA synthetic activity. Therefore, this 300-kDa fraction may contain a component which differs from the above enzymes yet is essential for initiation of DNA replication. PMID- 8513296 TI - Bovine lactoferrin in involuting mammary tissue. AB - Bovine lactoferrin in involuting mammary tissue was identified by immunohistochemistry and tissue explant culture. Immunoreactive lactoferrin was associated with mammary epithelial cells. Immunostaining for lactoferrin increased during involution, in contrast to declining immunostaining of epithelia for the milk-specific protein beta-lactoglobulin. Immunostaining for lactoferrin also was observed at the basal region of alveolar epithelia, perhaps in association with basement membrane components. Lactoferrin was preferentially synthesized in involuting mammary tissue compared with lactating tissue. Synthesis of lactoferrin in the involuting mammary gland occurs despite the apparent decline in synthesis of milk-specific proteins. PMID- 8513297 TI - The survival of cytochalasin-induced polykaryons following exposure to cytotoxic agents. AB - Using CHO-K1, HeLa S3 and two Walker lines (WR and WS) differentially sensitive to cis-diamminedichloroplatinum(II) (cisplatin), the survival after exposure to cisplatin, mitomycin C, vinblastine, vincristine or cytosine arabinoside has been determined either of clonogens or of cells rendered polyploid by post-exposure incubation in the presence of cytochalasin B (CB). It is suggested that the inhibition of cytokinesis by CB permits an assessment to be made of the fraction of damage whose expression is cell division-related, possibly including that resulting from a loss or malsegregation of genetic material. It was found that the response of polykaryons in comparison to clonogens was both agent- and cell line-dependent. After cisplatin exposure, polykaryon survival (defined as the ability to accumulate at least 16C DNA) declined exponentially with dose and was qualitatively, and to some extent quantitatively, similar to that observed previously after irradiation. In HeLa S3, giant cells induced by 10-20Gy irradiation in the absence of CB exhibited a radiation dose-dependent reduction in the relative frequency of highly polyploid cells which was similar to that observed in CB-induced polykaryons. PMID- 8513298 TI - Acid phosphatase activity in the larval salivary glands of developing Drosophila melanogaster. AB - Both the biochemical profile and the optical and fine structural localization of acid phosphatase activity in the larval salivary glands of developing Drosophila melanogaster is described. Biochemically, acid phosphatase shows peak activity in the glands of feeding larvae, followed by a marked decline. Directly preceding the onset of cell histolysis however, enzyme activity increases 1.5 fold and is maintained at this level. Histochemically, acid phosphatase activity initially appears as discrete point or lysosomal sources. As development proceeds, an intense and diffuse form of enzyme is seen, accompanying an extremely vacuolated cytoplasm. Ultrastructurally, the enzyme is located in lysosomes, Golgi elements, multivesicular bodies and both within, and on the extracisternal surface of the rough endoplasmic reticulum. This extracisternal or cytosolic form appears directly preceding cell lysis and eventually shows a comprehensive cellular distribution. Large numbers of acid phosphatase positive haemocytes are attached to the basal glandular surface at all developmental stages. In morphologically intact gland cells, discrete extracisternal enzyme activity appears associated with local areas of degradation. PMID- 8513299 TI - Inhibition of an endogenous growth-related proteinase enhances the recovery of a negative growth regulator from cultured human cells. AB - The possibility that a growth-related proteinase may act by degrading a negative growth regulatory protein has been investigated. Proteinase inhibitors which inhibit the enzyme also enhance the accumulation of the growth regulator by human fibroblasts. The negative growth regulator shows a similar specificity of inhibition of cellular growth to inhibitors of the growth-related proteinase. PMID- 8513300 TI - Breaking the adhesions of a cell with its substratum. AB - Investigation of the relative slowness with which trypsin detaches epithelial cells from their adhesions with a substratum suggests that the adherent surface of the cells is normally rather inaccessible to the enzyme. Trypsinisation of cells through a porous filter allowing access of the enzyme to the underside of the cells greatly accelerated detachment: a result consistent with this explanation. PMID- 8513301 TI - Phenotype of T cell clones obtained from bronchial biopsies and peripheral blood from three asthmatics. PMID- 8513302 TI - Arterial hypertension and cardiovascular damage in the elderly: focus on arterial stiffness and left ventricular hypertrophy. AB - Both aging and Arterial Hypertension (AH) cause a series of structural and functional changes in the cardiovascular apparatus. The reduction of aortic distensibility (RAD) and left ventricular hypertrophy (LVH) are, in particular, two significant markers of cardiovascular damage apart from being factors of serious and widespread morphological alterations. In this paper, the Authors analyze the effects of aging and of AH on the cardiovascular apparatus in order to find a possible clinical significance in relation to both RAD and LVH. PMID- 8513303 TI - Isolated systolic hypertension in the elderly: new insights. AB - Isolated Systolic Hypertension (ISH) is associated with a several-fold excess risk of mortality from myocardial infarction, stroke and cardiac failure. Decreased compliance of large arteries and altered timing of reflected waves from peripheral vessels account for the selective increase in systolic pressure present in the elderly. Due to the wide variability of blood pressure frequently seen in old subjects, ISH is not easy to recognize and diagnosis requires a long period of observation. Ambulatory blood pressure monitoring proved helpful in distinguishing between patients with true ISH and subjects with exaggerated alarm reaction to the pressure measurement. Although the increased risk of cardiovascular mortality is well established for ISH, there has been much debate over whether available antihypertensive treatment can prevent or delay cardiovascular complications in ISH. The results of the SHEP study, recently published, demonstrate positive effects of treatment in ISH, as stroke (-35%) and all cardiovascular events (-32%) were significantly reduced by low-dose chlortalidone alone or associated to atenolol or reserpine. PMID- 8513304 TI - Ambulatory blood pressure monitoring in elderly hypertensive patients. AB - Ambulatory blood pressure monitoring (ABPM) has been shown to provide a reliable estimation of hourly blood pressure values over the 24 hours. Favourable features of this technique are the lack of alerting reaction to automatic blood pressure readings, at variance from what usually occurs when blood pressure is measured in the doctor's office, and the ability of ABPM to provide information on the 24 hour blood pressure profile without interfering with the physiological nocturnal hypotension. Although automatic blood pressure readings obtained in free-moving subjects are not always accurate, ABPM has been shown to represent a useful approach to evaluate the efficacy of antihypertensive drugs, as it allows to compare the 24 hour blood pressure profile obtained before and during treatment. Its feasibility to this aim is emphasized by the reproducibility of 24 hour ambulatory blood pressure profiles, which do not show any placebo effect. ABPM has been also employed to investigate 24 hour blood pressure fluctuations and to monitor the antihypertensive treatment in elderly hypertensives, in whom the evaluation of the actual time-course of the drug-induced blood pressure reduction over the day and night represents a crucial problem. PMID- 8513305 TI - Camerano study on hypertension: the problem of blood pressure variability during medical visit. AB - The Camerano Study on Arterial Hypertension (AH) is a cross-sectional study, carried out on a wide population sample in a small town in Central Italy, and aimed at revealing the prevalence of certain characteristics of AH in the population examined. In particular, we studied some aspects of blood pressure (BP) levels during the medical visits. To evaluate the effects of the medical visit on BP levels, we divided the subjects into 3 groups: I) Hypertensive subjects, II) Treated hypertensive subjects, III) Normotensive subjects (control group). The Systolic Arterial Pressure (SAP) in normotensive subjects reached maximum levels during the first medical visit and then decreased in the following two controls (p < 0.001). The Diastolic Arterial Pressure (DAP) did not show any significant changes during the three measurements (p = n.s.). Instead the maximum level of SAP in the hypertensive group did not appear at the first measurement but only after 5 minutes and was seen to decrease towards the end of the visit (p < 0.001). Even DAP showed different levels compared to the normotensives: a decrease in BP levels was registered after 15 minutes respect to earlier measurements (p < 0.01). The levels of group II were similar to those of normotensive subjects. PMID- 8513306 TI - Coronary hemodynamics and the renin angiotensin system. AB - Coronary hemodynamics were investigated invasively at rest and during handgrip exercise in two groups of mild essential hypertensive subjects and in one group of renovascular hypertensive patients. The former subjects received either furosemide (50 mg/day for one week) to ensure activation of the renin-angiotensin system or an intravenous infusion of angiotensin II (AngII) at a subpressor dose (3 ng/kg/min for 15 minutes) and at a pressor dose (13 ng/kg/min for 15 minutes). Furosemide induced a significant reduction in coronary blood flow (CBF), a significant increase in coronary vascular resistance (CVR) and also blunted the increase in CBF during handgrip exercise. Captopril restored CBF and CVR to pretreatment values. Infusion of the subpressor dose of AngII decreased myocardial oxygen supply, both at rest and during exercise; the pressor dose increased myocardial oxygen supply at rest and blunted the expected increase in myocardial oxygen supply during exercise. Converting-enzyme inhibition in renovascular hypertension caused mean arterial pressure to decrease and CBF to increase significantly. The performance of handgrip exercise after cilazapril resulted in higher increases in CBF for a given increase in myocardial oxygen requirements. These data suggest that there is a negative interference by abnormally high plasma levels AngII with myocardial perfusion and that the AngII induced effects on coronary hemodynamics are reversed by converting enzyme inhibition. PMID- 8513307 TI - Ace-inhibitors and experimental atherosclerosis. AB - The role of renin-angiotensin system in the development of atherosclerosis is not yet defined, even though several actions of angiotensin II have been suggested as contributing to the development of the atherosclerotic lesion. Local renin angiotensin system may exert a variety of autocrine or paracrine influences on vascular tissue leading to important trophic and growth regulatory effects and participating to well known events in atherogenesis as control of smooth muscle cell growth and proliferation. The existence and the specific function of components of this system in blood vessels wall suggest its possible involvement in atherosclerotic process. On these bases, the antiatherogenic properties of ACE inhibitors have been recently evaluated in animal models where a protective effect of ACE-inhibition over the development of experimental atherosclerotic lesions has been observed. This favorable effect could follow the antihypertensive action of ACE-inhibitors even whether other potential mechanisms, including prevention of angiotensin II-induced vascular proliferation and interference with sympathetic nervous system activity and insulin sensitivity, have to be considered. Despite some clear-cut experimental evidences, the clinical importance of such findings as well as the precise mechanisms by which ACE-inhibition is able to interfere with the pathogenesis of atherosclerosis is still matter of debate and need to be assessed in future investigations. PMID- 8513308 TI - Ace inhibition in renal disease: risks and benefits. AB - The kidney is one of the principal target organs of hypertension and most diseases of the kidney are associated with blood pressure elevation. Studies in animal models of hypertensive renal disease have provided insights into the complex relationship between systemic and glomerular hypertension. The intrarenal renin-angiotensin system (RAS) appears to play an important role in the pathogenesis of progressive glomerular injury. Thus, angiotensin converting enzyme inhibitors (ACEi) may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. However, in contrast to their possible renoprotective effect in diabetic nephropathy or in renal hypertension, there are increasing evidence that, in the presence of a reduction in renal perfusion, intrarenal haemodynamic effect of ACEi may lead to compromised renal function. ACEi appear to have dual effects on renal function depending on the setting in which they are administered. PMID- 8513309 TI - Different sensitivity to hydrochlorothiazide and to potassium-canrenoate among essential hypertensive patients. AB - We compared the response of blood pressure (BP) to either K-Canrenoate (K-Can) or hydrochlorothiazide (HCTZ) in 26 mild-to-moderate essential hypertensives in a double-blind, cross-over design over 2 months each. The dose was 12.5 mg o.d. for HCTZ and 50 mg o.d. for K-Can: dosing was doubled after 1 month if seated diastolic BP was > or = 95 mmHg. Eight pts were "selective responder" to the lowest dose of HCTZ (HCTZ-R), and 6 to K-Can (K-Can-R). Seven pts had their high blood pressure controlled by the highest dose of both drugs and 4 were insensitive to both. One pt dropped out during HCTZ for low plasma K+, and 3 during K-Can (nausea and dizziness: 2 pts; plasma creatinine rise: 1 pt). All these side effects were reverted after drug withdrawal. HCTZ-R and K-Can-R differed for PRA (1.4 +/- 0.6 vs 0.8 +/- 0.4 Ang I ng/ml/h, p < 0.05) and Na-K-Cl cotransport (230 +/- 39 vs 372 +/- 24 mumolNa/L RBC/h, p < 0.01). Our data suggest the existence of a subgroup of essential hypertensives surprisingly insensitive to HCTZ, characterized by a "low" PRA and by a Na(+)-K(+)-Cl- cotransport higher than the HCTZ-R. Their selective response to K-Can suggest a peculiar pathogenetic mechanism underlying their high blood pressure. PMID- 8513310 TI - Middle term evaluation of amlodipine vs nitrendipine: efficacy, safety and metabolic effects in elderly hypertensive patients. AB - The aim of the study was to evaluate, in a population of elderly hypertensives, the efficacy for 24 hours, the safety and the effects on carbohydrates and lipids metabolism of amlodipine (A) and nitrendipine (N). After a 3-week placebo wash out, 50 patients with mild to moderate essential hypertension (HBP) or isolated systolic hypertension (ISH), were randomized in 4 groups treated with once-daily A 5,10mg or N 10,20mg increasing until patients responded to treatment. All subjects were submitted to a 24-hour non invasive ambulatory blood pressure monitoring (ABPM) at the start of the study (t0) and after four weeks of therapy (t4). It was registered a mean daily reduction in the pressure load of 15.0% in group A, 14.1% in group B, 13.9% in group C and 15.6% in group D; (p < 0.001). 82% of the patients treated with A and 85% treated with N resulted "responder". The metabolic parameters considered showed no significant changes. The overall incidence of adverse effects were temporary and extremely limited (2%). As monotherapies, amlodipine and nitrendipine are both suitable for the management of mild to moderate hypertension in elderly. PMID- 8513311 TI - The four seasons of anti-hypertensive therapy. AB - The development of anti-hypertensive therapy and its achievements over the last 40 years are reviewed. The following are identified as the still unanswered questions: the pharmacological treatment of mild hypertension; the limited efficacy of anti-hypertensive therapy in the reduction of the number of myocardial infarctions; the negative effect of some types of antihypertensive treatment on plasma lipids; the lack of efficacy of some drugs in reducing left ventricular hypertrophy; the difficulty in establishing the optimal levels of blood pressure and often the difficulty in achieving those levels. PMID- 8513312 TI - Preliminary morphometric data on lipid lesion distribution in aortas of young people (WHO-ISFC PBDAY study). AB - As the Morphometric Reference Center of the WHO-ISFC PBDAY Project (Pathobiological Determinants of Atherosclerosis in Youth) we are studying lesion involvement of left hemiaortas of young people from different parts of the world. Gross specimens were stained and photographed at the Malmo reference Center (Dir. Prof. N.H. Sternby). Percentage of lipid lesions were evaluated and probability maps of lipid lesion distribution at the aortic surface were obtained by image processing. In all samples from Italy, Mexico and Sri Lanka, high probability of lipid lesion occurrence was found between the emergences of the intercostal arteries, next to the emergence of the celiac trunk, between the emergence of the superior and inferior lumbar arteries and between the emergence of the 1st and the 2nd mesenteric arteries. Our data reveal that a) lipid lesions are localized in low shear-stress regions or in turbuecent regions; b) our samples taken from groups of different geographical origin present the same lipid lesion distribution at the aortic surface. PMID- 8513313 TI - Carotid atherosclerotic disease: role of hypertension and other risk factors. AB - 1224 out-patients who consecutively underwent a Biosound examination of carotid arteries were retrospectively analyzed in order to estimate prevalence of carotid lesions and the role played by age, sex and major vascular risk factors with respect to carotid atherosclerosis. They were subdivided in asymptomatic and symptomatic subjects, making a distinction in both subgroups between patients with (RF+) or without (RF-) major vascular risk factors. Carotid lesions were present in 41% of asymptomatic RF- subjects; in 53% of asymptomatic RF+ subjects; in 53% of symptomatic RF- subjects and in 75% of symptomatic RF+ subjects. Carotid disease increases along with age, being more frequent in men than in women. The logistic regression model has then shown that increasing age, male gender, cigarette smoking and hyperlipidaemia are predictors of carotid atherosclerosis, while hypertension has been proved to play significant role only in the age class 61-69 yr. PMID- 8513314 TI - Non invasive evaluation in cerebrovascular study: possibility and prospects. AB - The authors outline the importance of the global investigation of the cerebrovascular system in order to obtain more exact information about the ethiopathology of vascular ischaemic brain disease. Each patient is always submitted to the following investigations: Duplex scanner of epiaortic vessels, Transcranial doppler and echocardiographic screening in our vascular laboratory; moreover, when haemodynamic carotid artery stenosis is present, duplex scanner of femoro-popliteal vessels and microcirculatory study of the brain with Zenon133, via inhalation, were undertaken. In the second part of the study the authors refer a relationship between the instrumental doppler signal and the real risk evidenced by techniques which can provide information on the composition, structure and stability of the plaques and correlate this information with the data from the doppler analysis. Instrumental techniques such as thermal analysis, atomic absorption spectroscopy, ICP analysis and IR spectroscopy were used to carry out this study. PMID- 8513315 TI - Hypertension and other risk factors in peripheral arterial disease. AB - Aim of this study has been to evaluate the prevalence of arterial hypertension and other risk factors in patients suffering with PAD in two clinical samples (1.: 102 patients with PAD, 69 M, 33 F, studied in our angiology laboratory, matched for sex and age with 102 healthy volunteers; 2.: 184 hospitalized patients, 80 M, 104 F, mean age 57.2 +/- 10.8, with PAD) and in two epidemiological studies (1.: Trabia Study, 835 subjects; and 2.: Casteldaccia Study, 723 subjects). All patients performed a full clinical and laboratory examination, including the determination of the ankle/arm pressure ratio (Winsor index, positive for PAD when lower than 0.95). In the first clinical study we observed a significantly (p < 0.01) greater prevalence of arterial hypertension (51.9 vs 9.8%), hypercholesterolemia (48.2 vs 21.6%), hypertriglyceridemia (53.7 vs 26.1%), smoking habit (64.3 vs 44.2%), and hyperglycemia (26 vs 7.9%) in PAD patients than in controls. In the second clinical study, considering separately the patients under and over 65 years, all risk factors resulted more prevalent in younger people than in the aged, except diabetes and hypertension. PMID- 8513316 TI - Hypertension and atherosclerosis in the elderly: pathogenetic common mechanism and intervention strategies. AB - Hypertension is the leading cause of death in the elderly in Western countries. The Authors remark that hypertension is not only a purely hemodynamic phenomenon, but is a multifaceted disease frequently associated with metabolic disorders in the elderly. Among the latter, hyperinsulinism could be the linking pathogenetic factor with atherosclerosis progression. Then the Authors suggest a unitary pathogenetic hypothesis of hypertension and atherosclerosis. The crucial points are the inborn alteration of cellular sodium transport systems and the modulating action of environmental factors, first of all insulin. According to this hypothesis, the goal of the management of elderly hypertensives is the prevention of the fatal or invalidant cerebro- and cardiovascular event. To follow a good "pathogenetic" treatment of elderly hypertension and atherosclerotic process evolution, the first step is a dietetic approach avoiding acute load of sodium and lipids. Furthermore, the pharmacological treatment with calcium antagonists and ACE inhibitors is respectful of associated metabolic disorder and positively modulate the cellular sodium transport systems activity. PMID- 8513317 TI - Camerano study on hypertension: association between arterial hypertension and cardiovascular risk factors. AB - The Camerano study on Arterial Hypertension (AH), was a cross-sectional study carried out on a population living in a small town in central Italy. Its aim was to show the prevalence of certain characteristics of AH. We studied the association between AH and other well-known cardiovascular risk factors (CRF) such as: hypercholesterolemia, hypertriglyceridemia, cigarette smoking, hyperglycemia, obesity and in particular the hereditary factor, evaluated as the degree of association between the AH of the subject and that of his parents. The results reveal a significantly high association between AH and all the CRF examined. Subjects suffering from AH had double the chance of concomitant another CRF compared to the normotensives. If three CRF are present at the same time, then the hypertensive subjects are three times as many. When hereditary factors are evaluated, then subjects with two hypertensive parents have twice as much probability of developing AH compared to subjects from a normotensive family. PMID- 8513318 TI - APP717 and Alzheimer's disease in Italy. PMID- 8513319 TI - Genomic mismatch scanning: a new approach to genetic linkage mapping. AB - Genomic mismatch scanning (GMS) is a new method of genetic linkage analysis that does not require conventional polymorphic markers or gel electrophoresis. GMS is ideally suited to affected-relative-pair mapping. DNA fragments from all regions of identity-by-descent between two relatives are isolated based on their ability to form extensive mismatch-free hybrid molecules. The genomic origin of this selected pool of DNA fragments is then mapped in a single hybridization step. Here we demonstrate the practicality of GMS in a model organism, Saccharomyces cerevisiae. GMS is likely to be applicable to other organisms, including humans, and may be of particular value in mapping complex genetic traits. PMID- 8513320 TI - Expression pattern of the Kallmann syndrome gene in the olfactory system suggests a role in neuronal targeting. AB - Kallmann syndrome is a genetic disorder characterized by a defect in olfactory system development, which appears to be due to an abnormality in the migration of olfactory axons and gonadotropin releasing hormone (Gn-RH) producing neurons. The X-linked Kallmann syndrome gene shares significant similarities with molecules involved in neural development. We have now isolated the evolutionarily conserved chicken homologue of the Kallmann gene. In the developing and adult chicken, high levels of expression were found in the mitral cells of the olfactory bulb (the target of olfactory axons) and in the Purkinje cells of the cerebellar cortex, both areas affected in patients with Kallmann syndrome. We propose a model in which the Kallmann syndrome gene product is a signal molecule required for neuronal targeting throughout life. PMID- 8513321 TI - Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31. AB - Glaucoma is a significant cause of blindness world wide. There is evidence to suggest that at least a subset of the disease is determined genetically. We studied 37 members of a family affected with an autosomal dominant form of juvenile open angle glaucoma and 22 were found to be affected. Linkage analysis using short tandem repeat markers mapped the disease-causing gene to chromosome 1q21-q31. Eight markers were significantly linked (Zmax > 3.0) to the disease, with the highest lod score 6.5 (theta = 0), provided by D1S212. The atrial natriuretic peptide (ANP)/receptor system has been proposed to have a role in glaucoma and one of the ANP receptor genes maps to chromosome 1q. PMID- 8513322 TI - Finding similarities and differences among genomes. PMID- 8513323 TI - A new locus for autosomal dominant retinitis pigmentosa on chromosome 7p. AB - Autosomal dominant retinitis pigmentosa (adRP) is known to result from mutations in two different retinal genes--rhodopsin and peripherin--while a third locus has been implicated by linkage data. However, families have been reported in which all three known loci have been excluded. We report linkage of adRP in one such family to two microsatellite markers on chromosome 7p. D7S435 has previously been localized to 7p13-15.1; D7S460, previously only localized to chromosome 7, maps to within 2 cM of D7S435 with a lod score of 12.15. Two point linkage analysis between these markers and adRP gave lod scores of 5.65 (theta = 0) and 4.19 (theta = 0.046) for D7S460 and D7S435, respectively. Multipoint analysis gave a maximum lod score of 8.22. These data strongly suggest a new adRP locus on chromosome 7p. PMID- 8513324 TI - Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7q. AB - Retinitis pigmentosa is a group of clinically and genetically heterogeneous retinopathies and a significant cause of worldwide visual handicap. We have typed DNA from members of a Spanish family segregating an autosomal dominant form of retinitis pigmentosa (adRP) using a large series of simple sequence polymorphic markers. Positive two-point lod scores have been obtained with fifteen markers including D7S480 (theta max = 0.00, Zmax = 7.22). Multipoint analyses using a subset of these markers gave a lod score of 7.51 maximizing at D7S480. These data provide definitive evidence for the localisation of an adRP gene on chromosome 7q, and highlight the extensive genetic heterogeneity that exists in the autosomal dominant form of this disease. PMID- 8513325 TI - A molecular variant of angiotensinogen associated with preeclampsia. AB - Pregnancy-induced hypertension (PIH) is a heterogeneous disorder which complicates 5-7% of all pregnancies and remains a leading cause of maternal, fetal and neonatal morbidity and mortality. Severe preeclampsia is the most distinctive and life-threatening form; a multi-system disorder more common in first pregnancies, it is characterized by high blood pressure and proteinuria. In a series of Caucasian women with pregnancy-induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension. This finding is corroborated in a sample ascertained in Japan. Together, these observations support a new pathophysiological interpretation of preeclampsia and of its relation to some forms of essential hypertension. PMID- 8513326 TI - A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa. AB - Recessive dystrophic epidermolysis bullosa is a severe mutilating genodermatosis. Previous ultrastructural demonstrations of altered anchoring fibrils, and recent genetic linkage analyses have suggested that type VII collagen, the major component of anchoring fibrils, is a candidate gene. We have identified a homozygous methionine-to-lysine mutation in two affected siblings, while their unaffected mother and half-brother are heterozygous carriers. The mutation resides in a highly conserved region of the C-terminus of type VII collagen, strongly suggesting that it is the cause of the disease in this family. PMID- 8513327 TI - A tandem duplication in the D-loop of human mitochondrial DNA is associated with deletions in mitochondrial myopathies. AB - About 40 per cent of patients with mitochondrial myopathies have two populations of mitochondrial DNA (mtDNA) in muscle, one of which is deleted. All patients with single mtDNA deletions and neurological disease are sporadic cases, suggesting that deletions arise as fresh mutational events. We have detected a low abundance heteroplasmic tandem duplication involving the displacement loop of mtDNA in 18 of 58 patients with deletions and 5/5 of their mothers, but not in normal subjects. The location of the duplication to a region that controls both replication and transcription of mtDNA could explain features suggesting mild mitochondrial dysfunction in the muscle biopsies of three patients' mothers, and a predisposition to deletion. PMID- 8513328 TI - Genes, phenotypes and hypertensive pregnancies. PMID- 8513329 TI - Origin of the expansion mutation in myotonic dystrophy. AB - Myotonic dystrophy (DM) is caused by the expansion of a CTG trinucleotide repeat. The mutation is in complete linkage disequilibrium with a nearly two-allele insertion/deletion polymorphism, suggesting a single origin for the mutation or predisposing mutation. To trace this-ancestral event, we have studied the association of CTG repeat alleles in a normal population to alleles of the insertion/deletion polymorphism and of a (CA)n repeat marker 90 kilobases from the DM mutation. The results strongly suggest that the initial predisposing event(s) consisted of a transition from a (CTG)5 allele to an allele with 19 to 30 repeats. The heterogeneous class of (CTG)19-30 alleles which has an overall frequency of about 10%, may constitute a reservoir for recurrent DM mutations. PMID- 8513330 TI - An alternative dystrophin transcript specific to peripheral nerve. AB - Transcription of the 2.5 megabase dystrophin gene gives rise to multiple isoforms. We describe a 5.2 kilobase transcript, expressed specifically in peripheral nerve, that initiates at a previously unrecognized exon located approximately 850 basepairs upstream of dystrophin exon 56. The likely product of this transcript (Dp116) is detected by C-terminal dystrophin antibodies exclusively in peripheral nerve and cultured Schwann cells. Dp116 is located along the Schwann cell membrane but is not present in the compact myelin lamellae or in axons. Dp116 lacks actin-binding and spectrin-like rod domains, arguing that it functions differently in the Schwann cell than does the major dystrophin transcript in muscle. PMID- 8513331 TI - Questions of expansion. PMID- 8513333 TI - IGF2 is parentally imprinted during human embryogenesis and in the Beckwith Wiedemann syndrome. AB - The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith-Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome. PMID- 8513332 TI - Dystrophin expression in the human retina is required for normal function as defined by electroretinography. AB - We have studied retinal function by electroretinography in five Becker and six Duchenne muscular dystrophy patients. All had abnormal electroretinograms with a markedly reduced amplitude for the b-wave in the dark-adapted state. Using three antisera raised to different domains of dystrophin, we identified dystrophin in the outer plexiform layer of human retina. The retinal dystrophin is present in multiple isoforms as the result of alternative splicing. The localization of dystrophin to the outer plexiform layer coincident with the abnormal b-wave suggests that dystrophin is required for normal retinal electrophysiology. PMID- 8513335 TI - A DNA insertional mutation results in microphthalmia in transgenic mice. AB - Transgenic mice were produced by microinjection of a human A gamma-globin gene construct containing site 2 of the locus control region and the A gamma-globin gene with its 3' enhancer sequence. One transgenic mouse line (5'HS2 gamma en91) displayed an altered phenotype when the insertion event of this transgenic line was homozygous. These animals lack the normal pigmentation seen in their hemizygous and non-transgenic littermates, thus appearing white with unpigmented eyes. In addition, their eyes are underdeveloped, consistent with the phenotype associated with mutations at the microphthalmia (mi) locus. Backcrosses of transgenic mice with mi mutant mice result in phenotypes showing a lack of complementation, demonstrating that the site of transgene insertion is allelic with mi. Electron microscopic analysis of hair follicles and culturing of melanocytes from the skin of transgenic animals reveals an absence of cutaneous melanocytes in homozygotes and aberrant growth and morphology of the melanocytes isolated from hemizygous animals. The results presented here summarize the effects of this new allele of the mi locus. PMID- 8513334 TI - Expression of the lacZ gene targeted to the HPRT locus in embryonic stem cells and their derivatives. AB - Transgenes in mice often exhibit different expression patterns in different transgenic lines. While the basis for this phenomenon is not understood, it is widely believed that the site at which the transgene becomes integrated into the mouse genome is a major factor in determining the pattern of expression. Most transgenic mice have been produced by microinjection of DNA into the male pronucleus, which results in integration of tandem arrays of the transgene at random chromosomal sites. In the experiments described in this report, electroporation of embryonic stem (ES) cells was used to place single copies of a lacZ transgene into either random sites or into the HPRT (hypoxanthine phosphoribosyl transferase) locus of the mouse genome. Expression of lacZ was assayed by histochemical staining for Escherichia coli beta-galactosidase activity in ES cells and in differentiated derivatives obtained by teratocarcinoma formation. Several of the randomly integrated cell lines expressed lacZ at high levels in a variety of cell types present in the tumours, but most notably in epithelial cells. Targeted cell lines with lacZ in opposite orientation to the direction of HPRT gene transcription also expressed well in epithelial cells, but the targeted cell lines did not express in a wider variety of cell types than some of the nontargeted cell lines. Targeted cell lines transcribing lacZ in the same orientation as HPRT transcription did not express high levels of lacZ in any differentiated cell type. Analysis of transcripts suggested that this orientation effect may have been the result of transcriptional interference perpetrated by the HPRT gene promoter. PMID- 8513336 TI - The majority of G0 transgenic mice are derived from mosaic embryos. AB - Most transgenic mice are generated by the direct microinjection of DNA fragments into the pronuclei of fertilized eggs. It has been generally assumed that the majority of integration events occur prior to the first round of chromosomal DNA replication (Palmiter and Brinster, 1986). In this study we have determined by comparison of PCR, Southern blot and transmission frequencies that at least 62% of integration events generate a mosaic (somatic and/or germline) G0 transgenic mouse. Furthermore, the statistical probability of transgene-containing cells segregating to the various early embryo lineages implies that this is probably an underestimate of the true mosaic frequency. Thus, the majority of DNA injected into fertilized mouse eggs intergates after the first round of chromosomal DNA replication, therefore most G0 transgenic mice are derived from a mosaic embryo. PMID- 8513337 TI - Tagging genomic sequences that direct transgene expression by activation of a promoter trap in plants. AB - As part of a gene tagging strategy to study the developmental regulation of patterns of plant gene expression, a promoterless uidA (gusA) gene, encoding the beta-glucuronidase (GUS) reporter, was introduced into populations of tobacco, Arabidopsis and potato by Agrobacterium-mediated gene transfer. The objective was to generate random functional fusions following integration of the gusA gene downstream of native gene promoters. We describe here a detailed analysis of levels and patterns of gusA activation in diverse organs and cell types in those populations. gusA activation occurred at high frequency in all three species, and unique patterns of fusion gene expression were found in each transgenic line. The frequency of gusA activation was differentially biased in different organs in the three species. Fusion gene activity was identified in a wide range of cell types in all organs studied, and expression patterns were stably transmissible to the T2 and T3 progeny. Developmentally-regulated and environmentally-inducible expression of gusA is described for one transgenic line. Phenotypic variants were detected in the transgenic population. These results demonstrate the potential of T-DNA insertion as a means of creating functional tags of genes expressed in a wide spectrum of cell types, and the value of the approach as a complement to standard T-DNA insertional mutagenesis and transposon tagging for developmental studies is discussed. PMID- 8513338 TI - Expression of c-fos and c-myc protooncogenes in an immortalized hepatocyte line harbouring SV40 T antigen and hGH as transgenes. AB - A clonal hepatocyte line (FMH-202-2), derived from livers of fetal transgenic mice harbouring human growth hormone (hGH) and SV40 T antigen as transgenes, was used in the investigation of protooncogene expression involved in liver-specific growth control and/or in hepatocellular transformation. In this model system, representing an immortalized, yet untransformed phenotype, the transgenes hGH and SV40 T antigen were expressed constitutively. The c-fos protooncogene was induced by incubation with insulin, epidermal growth factor (EGF) and insulin-like growth factor (IGF-I) in a transient manner comparable to its expression in primary murine hepatocytes. Elucidation of second messenger mechanisms demonstrated that c-fos induction by hepatotrophic growth factors was not mediated by protein kinase C. In contrast to primary hepatocytes, the c-myc protooncogene exhibited a constitutive expression pattern which was independent of growth factor stimulation. These results indicate that apart from hGH and SV40 T antigen, c-myc may play a role in cellular immortalization, but that constitutive expression of these genes, even in combined coexpression, does not suffice to induce the transformed phenotype. PMID- 8513339 TI - Glucoamylase overexpression in Aspergillus niger: molecular genetic analysis of strains containing multiple copies of the glaA gene. AB - A strategy, based on the usage of the amdS selection marker and a cosmid vector containing four copies of the glucoamylase gene (glaA), was developed to obtain glucoamylase (GLA)-overproducing A. niger strains. With this strategy, fungal strains carrying up to 200 copies of the glaA gene could be isolated at a relatively high frequency. In each transformant analysed, integration occurred in a single chromosome. A significant increase in the extracellular GLA production was observed in most of the transformants carrying multiple copies of the glaA gene. Further analysis showed that the amount of GLA that is produced was not proportional to the number of glaA copies in these transformants. However, the level of GLA production clearly correlated with the amount of glaA mRNA produced in these transformants. From these results it is concluded that GLA production is limited at the level of transcription. PMID- 8513341 TI - [HIV infection in Norway]. PMID- 8513340 TI - An SAR sequence containing 395 bp DNA fragment mediates enhanced, gene-dosage correlated expression of a chimaeric heat shock gene in transgenic tobacco plants. AB - A 395 bp fragment located downstream from the soybean heat shock gene Gmhsp 17.6 L exhibits several characteristics of scaffold attachment region (SAR) sequences. It contains matrix consensus elements, a topoisomerase II binding sequence and it associates with the isolated nuclear scaffold of soybean in vitro. Chimaeric genes containing the SARL fragment either at one side (5' or 3') or at both sides of a heat shock promoter-regulated beta-glucuronidase reporter gene were constructed. A five- to nine-fold increase of heat-inducible beta-glucuronidase activity was observed in transgenic tobacco plants containing constructs with SARL fragments either at both sides or with at least one SARL copy located upstream from the reporter gene. The gene copy number is positively correlated with the level of heat-inducible reporter gene activity in these plants but positional effects are not entirely eliminated. Thus, SAR sequences may potentially be used to increase gene expression, via as yet unknown mechanisms, and to reduce adverse effects on the expression of multiple gene copies in transgenic plants. PMID- 8513342 TI - [HIV and AIDS. An encounter with ourselves]. PMID- 8513343 TI - [HIV and AIDS--here and now]. PMID- 8513344 TI - [HIV and AIDS--an oasis for the HIV-positive]. PMID- 8513345 TI - [HIV-positivity in the outer reaches of Norway]. PMID- 8513346 TI - [HIV and AIDS in the world today]. PMID- 8513347 TI - [Nursing care of AIDS patients in Ulleval hospital]. PMID- 8513348 TI - [HIV and AIDS. LMA (National Association against AIDS) seeks annual TV action]. PMID- 8513349 TI - [HIV and AIDS--useful addresses and telephone numbers]. PMID- 8513351 TI - [HIV and AIDS around the world]. PMID- 8513350 TI - [HIV and AIDS. Home care project in Rwanda]. PMID- 8513352 TI - [Voluntary active euthanasia--attitude among nursing students]. PMID- 8513353 TI - [Technology and nursing care]. PMID- 8513354 TI - [Deficiency in care. Prevention of the anxiety stage]. PMID- 8513355 TI - [Can we build bridges if we make little effort?]. PMID- 8513356 TI - [We believe that most professional problems can be blamed on leadership problems]. PMID- 8513357 TI - [Article is unjustified and negative]. PMID- 8513358 TI - [It is the department head's task to follow up on its personnel]. PMID- 8513359 TI - [Philippine nursing education is more comprehensive than the Norwegian one]. PMID- 8513360 TI - [Our education includes efficiency and planning]. PMID- 8513361 TI - [How is professional ethics based on confidentiality and solidarity?]. PMID- 8513362 TI - [Insufficient follow-up of new employees is often a problem]. PMID- 8513363 TI - [What should discussion serve?]. PMID- 8513364 TI - [HIV and AIDS--living with dignity]. PMID- 8513365 TI - The new HCFA chief. Interview by Renee Blankenau. AB - Bruce Vladeck, the new HCFA administrator, shares his perspectives on HCFA's relationship with the hospital community, the concept of health networks, the role of Medicare and Medicaid in the reform scenario, and a variety of other topics. PMID- 8513366 TI - Exploring the continuum. In uncharted waters, health networks map continuums of care--and their futures. PMID- 8513367 TI - Confused consumers. When given options, what health plans do consumers choose- and why? PMID- 8513368 TI - A dose of pharmaco-economics. Can health networks learn from the drug policies of managed care plans? PMID- 8513369 TI - Western Michigan. Providers embark on journey to create a regional health care system. PMID- 8513370 TI - CDF's (Children's Defense Fund) Carol Regan. Interview by Karen Gardner. PMID- 8513371 TI - Data watch. Despite storm of rules, hospital-physician relations remain intact. PMID- 8513372 TI - Merging? Here's how to inform the media and your community. PMID- 8513373 TI - Will college nursing education include managed care? PMID- 8513374 TI - New performance measures will yield comparative data on HMOs. PMID- 8513375 TI - Hospitals, allieds ask JCAHO to reconsider indicator mandate. PMID- 8513376 TI - States move forward with health reform despite national efforts. PMID- 8513377 TI - Challenge of poverty: some advice for advocates of managed competition. PMID- 8513378 TI - Will the voluntary medical staff remain intact? No. PMID- 8513379 TI - Will the voluntary medical staff remain intact? Yes. PMID- 8513380 TI - Status of clinical engineering title. PMID- 8513381 TI - Calibration and PM scheduling. PMID- 8513382 TI - Responsibilities and training needs of BMETs in Veterans Affairs and large private-sector hospitals. BMET job descriptions vary widely. PMID- 8513383 TI - A proposed model for designing clinical engineering department protocols. Some ideas for implementing and augmenting your hospital's policies and procedures. PMID- 8513384 TI - A flexible information management system. Better information management means increased productivity. AB - While the finite details and program listings have been purposely excluded, the system described in the preceding text provides the basis for a relatively inexpensive equipment management system. The Biomedical Engineering Department at Rochester General Hospital has utilized this system to increase productivity levels by nearly 15% since implementation in early 1990. With a seven-member technical staff this increase in productivity translated into the addition of approximately 2,100 man-hours in 1991, the equivalent of one extra person. The department was able to utilize these hours to expand into new areas of responsibility and reduce the average service cost per item by 58%. As previously indicated, the key to the system presented is flexibility. There is no hard and fast rule for this system, just a simple, common sense guideline: continuously review, revise, and develop the program. While adherence to this process provides a solid basis for any system whether computerized or manual, it is intended for use only as a "tool," not as a substitute for clinical engineering knowledge and instincts. The ease and speed with which studies are formulated facilitate the large-scale data dissection process so often associated with equipment management programs. Correspondingly, the ability to modify database structures and applications provides the means for expansion and refinement of the system on an ongoing basis. PMID- 8513385 TI - Implications for clinical monitoring of intra-arterial blood pressure based on the frequency content of worst-case pressure waveforms. AB - There is no consensus regarding the minimum acceptable frequency response for a system intended for routine monitoring of invasive blood pressure in the operating rooms or intensive care units. Part of the problem stems from the diverse criteria used to validate faithful reproduction of the pressure waveform and waveform parameters. Another part of the problem is related to the site of pressure measurement: some anatomic sites have waveforms that are more difficult to reproduce than others. The most often quoted criteria, around which many clinical blood pressure monitoring systems have been constructed, are based on reproduction of all details of the pressure waveform from the most demanding anatomic sites. However, the routine clinical setting is primarily concerned with obtaining accurate values for systolic and diastolic blood pressures as recorded from peripheral arterial sites. This study was designed to obtain worst-case, in the sense of most difficult to measure, blood pressure waveforms from the femoral artery and the left ventricle using a canine model. The purpose of worst-case analysis was to create pressure waveforms that were at both extremes of frequency content, i.e., a rapidly beating heart with extraordinary contractility and a more slowly beating heart with little contractility. The premise of this type of analysis is that all naturally occurring pressure waveforms within a very broad physiologic range would fall within these extremes; therefore, the ability to measure the extreme waveforms would imply the ability to measure all those in between. Worst-case waveforms chosen from among 360 pressure waveforms were analyzed to determine the minimum frequency content of each waveform that would be required for faithful reproduction of systolic and diastolic pressures and the dP/dt. The criterion for faithful reproduction was chosen to be +/- 5% or 1 mmHg, whichever is greater. Data from the worst-case canine study, with supporting data collected intraoperatively from three patients, demonstrate that systolic and diastolic pressures can be obtained from a peripheral measurement site within 5%, requiring only two harmonics in conjunction with an appropriately low-pass filtered catheter manometer system. Left ventricular pressure waveforms require five harmonics to reproduce the systolic and diastolic pressures within 5% or 1.0 mmHg, whichever is greater. Determination of the maximum dP/dt within +/- 5% from the worst-case peripheral and left ventricular waveforms required 20 and 22 harmonics, respectively. PMID- 8513386 TI - A new sodium-nitroprusside-infusion controller for the regulation of arterial blood pressure. AB - Automatic optimization of the infusion rate of sodium nitroprusside (SNP) is achieved by an integrated hardware-software closed-loop controller implemented as a small bedside device. A microprocessor-based blood pressure monitor controls an infusion pump. The shape of the arterial pressure wave is digitally sampled; its analysis incorporates artifact-detection and -rejection routines. The implemented algorithm applies a rule-based closed-loop control that incorporates fuzzy logic. The system models the decision-making ability of the expert, instead of trying to model the patient's physiologic dynamics. Several internal fuzzy-state variables are defined to achieve a clear understanding of mean arterial pressure (MAP) evolution with time. The system performance is very robust, employing, under all possible situations, a sort of "common sense." A clinical trial of the controller was conducted in 60 patients requiring vasodilation therapy for systemic arterial hypertension following cardiac surgery, 20 who had conventional manual control by an experienced nursing staff and 40 who had automated closed-loop control. The first 240 minutes of the postoperative period were closely watched, taking into account 1) the percentage of time during which MAP was within the 10-mmHg wide frame above the target pressure (target gap); 2) the mean difference of pressure values that crossed the boundary of the target gap; 3) the mean SNP-infusion rate. With automatic control, the time mean arterial pressure values were located in the target gap during the first hour amounted to 72.8 +/- 6.7%, vs 51.2 +/- 10.3% in the manual-control group. In the second hour, it was 79.3 +/- 2.5% vs 67.4 +/- 11.7% (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513388 TI - Proceedings of the British Pharmacological Society Meeting, Joint Meeting with British Opioid Colloquium. 14-16 April 1993. Abstracts. PMID- 8513387 TI - Operational amplifiers. PMID- 8513389 TI - Loss of brain 5-HT2 receptors in Alzheimer's disease. In vivo assessment with positron emission tomography and [18F]setoperone. AB - Using [18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized [18F]setoperone in plasma, 18F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18F]setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69%; frontal, 69%; parietal, 55%; temporo-parietal, 54%; occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET. PMID- 8513390 TI - Rapid modulation of human cortical motor outputs following ischaemic nerve block. AB - The amplitudes of motor evoked potentials to transcranial magnetic stimulation from muscles immediately proximal to a temporarily anaesthetized (Bier's block) human forearm increase in minutes after the onset of anaesthesia and return to control values after the anaesthesia subsides. In order to determine the level at which the early modulation of human motor outputs takes place, we recorded maximal H reflexes, peripheral M responses, motor evoked potentials to transcranial magnetic stimulation, and motor evoked potentials to transcranial electrical stimulation and spinal electrical stimulation from a muscle immediately proximal to a limb segment made ischaemic by a pneumatic tourniquet. The amplitudes of motor evoked potentials to transcranial magnetic stimulation, but not to transcranial electrical stimulation and spinal electrical stimulation, were larger during ischaemia, implying that the site of change was in the motor cortex. The maximal H/M ratios were unaffected by ischaemia, indicating that alpha-motor neuron excitability to segmental Ia inputs remained unchanged. The map of cortical representation areas for this muscle obtained with transcranial magnetic stimulation was also enlarged. Taken together, our findings suggest that the temporary removal by ischaemic nerve block of myelinated afferent inputs reduces inhibition at the motor cortical level and that this disinhibition is responsible for the increased excitability of the corticospinal system. PMID- 8513391 TI - Multi-modal hemispatial deficits after left hemisphere stroke. A disorder of attention? AB - We report a patient who, after suffering infarcts involving the left temporo parietal and left anterior cingulate regions, performed significantly worse on a variety of motor, language and sensory tasks when he acted in or attended to right hemispace. Performance on a number of tasks was better when acting in near as compared with far peri-personal space and with his head deviated to the left as compared with the right. Additionally, performance with the 'unaffected' left hand was often worse in right as compared with left hemispace. We propose that his deficits are attributable to a disruption of a left hemisphere-specific attentional system which normally serves to regulate the activation and articulation of left hemisphere processing modules. PMID- 8513392 TI - Dementia associated with a 216 base pair insertion in the prion protein gene. Clinical and neuropathological features. AB - We report the clinical and neuropathological findings in a patient with a 216 base pair insertion in the prion protein (PrP) gene. She died aged 57 years after a 2.5-year illness characterized by falls, axial rigidity, myoclonic jerks and progressive dementia. There was no history of affected relatives. The pathological changes consisted of the deposition in cerebellum, basal ganglia and cortex of small plaques composed of variable amounts of amyloid and degenerative material which was associated with a marked macrophage reaction. The amyloid deposits in the cerebellum and basal ganglia gave a positive immunoperoxidase staining reaction for PrP. In some places plaques bore a resemblance to senile neuritic plaques and in the hippocampus there were abundant typical neuritic plaques giving positive staining reactions for beta-amyloid protein and tau protein, but not PrP. There were few neurons bearing neurofibrillary tangles. This is the first report of the neuropathological changes associated with this particular abnormality of the PrP gene and it seems to demonstrate a transition between the pathology of prion disease and that of Alzheimer's disease. The importance of PrP gene analysis to the understanding of neurodegenerative diseases is stressed. PMID- 8513393 TI - A serial study of psychometric and magnetic resonance imaging changes in multiple sclerosis. AB - Over a 6-month period, five patients with early relapsing--remitting multiple sclerosis and five with long-standing, benign multiple sclerosis underwent serial psychometric testing and contrast enhanced magnetic resonance imaging of the brain at 2-weekly or monthly intervals, respectively. All patients were individually matched with healthy controls who completed the same psychometric battery at the same time intervals. As a group, multiple sclerosis patients either made more errors or performed slower on all psychometric tasks than controls. In the control subjects and those patients with a stable brain lesion score, no consistent deterioration occurred in any test and the overall pattern was one of improvement over time commensurate with practice effects. However, patients with a deteriorating lesion score either showed a fall-off in performance on some psychometric tasks (patients 2, 3) or else an impaired ability to improve with practice on certain tests of attention and information processing speed (patient 10). PMID- 8513394 TI - Neurotrichinosis. A cerebrovascular disease associated with myocardial injury and hypereosinophilia. AB - The clinical features, brain computerized tomography (CT) scans and cardiological findings of nine patients with neurotrichinosis are reviewed. Neurological signs consisted of encephalopathy and focal deficits with small hypodensities in the cortex and white matter, detected by the CT scans. Various cardiovascular events were also observed in eight out of nine patients. They were usually concomitant with neurological symptoms and mainly consisted of myocardial injury as assessed by electrocardiographic and plasma creatine phosphokinase (CPK)-MB isoenzyme changes. The cardio-neurological syndrome developed early in the course of the disease at a time of marked hypereosinophilia and the percentage of patients with eosinophilia > or = 4000 mm3 was significantly higher in the patients with neurological dysfunction than in those without neurological signs. We selected the following criteria to describe the distinctive cardio-neurological syndrome related to trichinosis: (i) early onset of neurological symptoms (within a few days) after the first general symptoms; (ii) central nervous system involvement consisting of both diffuse encephalopathy and focal neurological deficits, usually of simultaneous onset; (iii) concomitant acute myocardial injury and/or infarction; (iv) marked hypereosinophilia (> or = 4000/mm3) at time of first cardio-neurological events; (v) brain CT scan showing small hypodensities in the hemispheric white matter or cortex. Post-mortem examination of one patient revealed ischaemic lesions with multiple arteriolar microthrombi in the brain and myocardium. This was consistent with the brain CT scan and electrocardiographic data and suggested that neurotrichinosis is an expression of a multi-organ disorder associated with hypereosinophilia, that is characterized in most patients by simultaneous neurological and myocardial manifestations basically related to ischaemia. PMID- 8513395 TI - The mitochondrial DNA transfer RNA(Lys)A-->G(8344) mutation and the syndrome of myoclonic epilepsy with ragged red fibres (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA. AB - The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role. PMID- 8513396 TI - Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study. AB - Positron emission tomography was used to measure regional cerebral blood flow (rCBF) in 12 patients with amyotrophic lateral sclerosis (ALS) and six age matched controls. Scans were performed at rest, and while subjects performed stereotyped and freely selected movements of a joystick with their right hand. Statistical parametric mapping was used to determine significant differences in rCBF between the two groups at rest and during activation. The ALS group showed no significant difference in global cerebral blood flow at rest compared with controls. However, rCBF at rest was significantly (P < 0.01) reduced in the ALS group in the primary sensorimotor cortex, the lateral premotor cortex, the supplementary motor area, the anterior cingulate cortex, the paracentral lobule and the superior and inferior parietal cortex. Comparison of the increase in rCBF caused by freely selected joystick movements over the resting state between the two groups of subjects showed significantly (P < 0.001) greater activation in ALS patients in the ventral third (face area) of the contralateral primary sensorimotor cortex and in the adjacent contralateral ventral premotor and parietal association cortices; significantly (P < 0.01) greater activation of the contralateral anterior insula and the ipsilateral anterior cingulate cortex (dorso-caudal area 24) was also present in ALS patients. When a comparison of the rCBF response to the free selection task with that to the stereotyped task was performed between the two groups of subjects, ALS patients showed significantly impaired (P < 0.01) activation of the rostral anterior cingulate cortex (area 32), medial prefrontal cortex (area 10), left parahippocampal gyrus and retrosplenial cortex. The pattern of reduced rCBF at rest in ALS patients probably reflects a combination of neuronal loss in all areas of cortex projecting through the pyramidal tract together with loss of projections from the sensorimotor cortex to the motor association areas. The expansion of the upper limb output zone of the sensorimotor cortex in ALS patients during contralateral upper limb movement may represent cortical reorganization in response to Betz cell loss or corticospinal tract disruption. Abnormal recruitment of non-primary motor areas may also represent functional adaptation to a corticospinal tract lesion. Focally impaired activation of the medial prefrontal cortex and parahippocampal gyrus in ALS patients during the process of internal generation of movement could underlie the frontal lobe cognitive deficits reported in previous neuropsychological studies of ALS. PMID- 8513397 TI - Multiple sclerosis. Pathology of recurrent lesions. AB - Recent autopsy studies suggest that remyelinated shadow plaques located in otherwise intact white matter are the outcome of a previous single episode of acute demyelination. In the present study, of 98 remyelinated plaques examined in 15 patients with multiple sclerosis who died between 27 days and 5 years after clinical onset, 15 showed evidence of a superimposed new demyelinating lesion. Inspection of old shadow plaques in a separate series of patients with subacute and long-standing multiple sclerosis revealed that such lesions sometimes exhibit punched-out areas of demyelination and gliosis similar in size and shape to fresh lesions located within or overlapping remyelinated shadow plaques. The findings support magnetic resonance imaging evidence that local recurrence may be as important or more important than progressive edge activity in determining plaque growth and the conversion of nascent lesions into classical demyelinated plaques. The findings also support experimental evidence that recurrent demyelination of the same area of white matter may be one of the factors underlying failed remyelination in multiple sclerosis. PMID- 8513398 TI - Comprehension deficits elicited by electrical stimulation of Broca's area. AB - We report on three patients with intractable focal seizures arising from the language-dominant left hemisphere. In the work-up prior to surgical treatment, arrays of subdural electrodes were placed over the left temporal lobe and adjacent supra-Sylvian region. Electrical stimulation of the inferior frontal cortex language region ('Broca's area') produced marked interference with language output functions including speech arrest, slowing of oral reading, paraphasia and anomia. At some cortical language sites in this region cortical stimulation also produced language comprehension deficits, particularly in response to more complex auditory verbal instructions and visual semantic material. The severe impairment of comprehension verbal information was in clear contrast with ability to process non-verbal material, which was not affected. PMID- 8513400 TI - The oculo-auricular phenomenon. Findings in normals and patients with brainstem lesions. AB - The oculo-auricular phenomenon consists of bilateral coactivation of external ear muscles during lateral gaze. The electromyogram of the transverse auricular muscle was recorded in 25 healthy volunteers and 1186 patients. In normal subjects bilateral coactivation was observed with lateral gaze (96%), convergence (61%), active and intended head rotation (100%) and passive head rotation (50%). Uni- and bilateral labyrinthine excitation (60 and 80%) and proprioceptive input from the neck muscles (38%) are also effective. In patients with brainstem disease abnormal transverse auricular muscle coactivation is characterized by absence of activity in one or both ear muscles during lateral gaze in either or both directions. The most frequent abnormality was absence of transverse auricular muscle activity homolateral to right or left gaze (type Ia pattern). It was related to homolateral impairment of the blink reflex R1-response (90%) and the caloric response (90%), and to contralateral masseter reflex abnormality (70%). Electrophysiological data, clinical signs and imaging findings indicate that the type Ia pattern is caused by homolateral pontine or contralateral midbrain lesions. It is suggested that the supranuclear organization of the oculo auricular phenomenon is based on descending tracts crossing at a mid-pontine level. PMID- 8513399 TI - Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects. AB - In the present study, a comparison was made of the fatty acid composition of the grey and white matter of the frontal, parietal and parahippocampal regions of post-mortem brains of patients who had died with Alzheimer's disease (n = 15) and control postmortem subjects (n = 10). Diagnosis of Alzheimer-type disease was based on the presence of senile plaques and neurofibrillary tangles in post mortem sections. Several highly significant and specific differences were observed between the two groups. Adrenic acid (22:4 n-6) was three to four times higher in the grey matter but lower in the white matter in each of the three regions in the Alzheimer brains than in the control group. These alterations were compensated by reciprocal changes in 18:0 in the grey matter and 16:1 fatty acids in the white matter. There was no significant difference in the proportion of other fatty acids, including those of the n-6 and n-3 series, in either the grey or the white matter of any of the three regions of the two groups, except for a higher proportion of 22:6 n-3 in the parietal white matter in the Alzheimer patients. There was no significant relationship between the levels of the individual fatty acids and age at death. It is suggested that the alterations in the fatty acid composition observed in the brains of Alzheimer patients may be caused by an aberration in the system by which essential fatty acids are transported into the brain. PMID- 8513401 TI - Linkage analysis in British and French families with idiopathic torsion dystonia. AB - Idiopathic torsion dystonia is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. An idiopathic torsion dystonia locus has been mapped to chromosome 9q34 in one large non-Jewish and several Jewish kindreds in the USA. Linkage analysis was performed in 27 (26 British, one French) small families with idiopathic torsion dystonia, three of which were Ashkenazi Jewish, using the highly polymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34. The cumulative lod score for the more informative ASS locus at a recombination fraction of 0.001 was -6.72. A large component of this score was derived from three non-Jewish families, indistinguishable clinically from the others, in which individual lod scores excluded a disease locus tightly linked to ASS. Analysis of all the data using HOMOG showed significant heterogeneity, but evidence for linkage of an idiopathic torsion dystonia gene to 9q34 in a subset of families. The allelic association observed between ASS/ABL and idiopathic torsion dystonia in Ashkenazi families in the USA was also present in British Jewish kindreds. These data suggest genetic heterogeneity in idiopathic torsion dystonia but indicate the existence of a locus for idiopathic torsion dystonia at 9q34 in both Jewish and non-Jewish kindreds in the UK. PMID- 8513402 TI - Quantitative dendritic and spine analyses of speech cortices: a case study. AB - The present case study documents an unprecedented opportunity for correlative investigation of brain structure and function by quantitatively investigating the basilar dendritic systems of supragranular pyramidal cells in several cortical areas from a subject who had undergone electrical stimulation mapping 2 years prior to death. Electrical stimulation mapping results provided valuable functional information about the cortical areas removed for postmortem histological analysis. Morphometric analyses distinguished between proximal (first, second, and third order) and ontogenetically later developing distal (fourth order and above) basilar dendritic branches. In general, perisylvian language association stimulation sites (classical Wernicke's and Broca's areas) were characterized by different dendritic patterns than motor strip sites. In primary motor strip tissue blocks, proximal segments were longer than distal segments. In "higher order" elaborative cortical zones, distal segments were longer than proximal segments. Proximal segments outnumbered distal segments in primary motor zones, but the numerical difference between proximal and distal segments was reduced in the association areas. Finally, fourth order segments had significantly more dendritic spines than third order segments in all sites. These dendritic findings suggest a somewhat later ontogenetic development in classical Broca's and Wernicke's areas than in primary motor cortex. PMID- 8513403 TI - Hemispheric specialization or reading habits: evidence from lexical decision research with Hebrew words and sentences. AB - This paper reports the results of a lexical decision-visual hemifield protocol using Hebrew words and nonwords. The lexical decision task was combined with sentence priming to examine the impact of hemispheric specialization and sentence length. The data are relevant to the Kirsner and Schwartz (1986) hypothesis that reading habits can explain the oft-reported right visual field (RVF) superiority in linguistic tasks. Both the target stimuli and the sentence primes were in Hebrew and 26 male right-handed native Hebrew speakers served as subjects. Hebrew is written and read from right to left. Therefore, according to the favorable foveal viewing explanation (Kirsner & Schwartz, 1986), there should have been no RVF superiority. The results indicated, however, highly significant RVF superiority. Furthermore, priming sentences, written in Hebrew, should direct the attention of the subject to the left visual field in expectation of the appearance of a target word. Nevertheless, the RVF superiority was even more significant when target stimuli were preceded by priming sentences. Both results indicated that reading habits and directed reading attention cannot explain RVF superiority in lexical decision. PMID- 8513404 TI - Horizontal and vertical neglect dyslexia. AB - This case study concerns a 25-year-old right-handed male patient (G.G.) with post traumatic lesions involving the right temporal and occipital lobe as well as the basal forebrain of the same side. G.G., who had a visual field defect almost limited to the upper left quadrant, showed both left horizontal and lower vertical neglect dyslexia, disproportionately severe when compared with left and lower visuo-spatial neglect. This is the first case report of a patient whose neglect dyslexia for vertical stimuli depended upon stimulus orientation, i.e., errors affected the final letters of top-down words and the initial letters of the bottom-up ones. This implies that neglect dyslexia can affect the internal letter shape map not only along the horizontal, but also along the vertical axis. PMID- 8513405 TI - Chronic aphasia subsequent to striato-capsular and thalamic lesions in the left hemisphere. AB - The language abilities of a group of seven chronic aphasics with vascular lesions centered on the striato-capsular region and thalamus of the left hemisphere were described. A range of severity and types of chronic language disorder were documented through assessment using a battery of standardized language tests. The most common language disorder documented was a naming impairment of varying degrees of severity, exhibited by six of the seven cases. The majority of subjects made predominantly semantic errors in the naming task; however, each subject produced a variety of error types and there was no pattern of errors characteristic of the group. The language data obtained were used to evaluate previously developed models of the role of the subcortical structures in naming functions. PMID- 8513406 TI - A reappraisal of localization theory with reference to aphasia. Part 1: Historical considerations. AB - Aphasiology is deeply rooted in observations of human behavior, in classification systems for speech and language disturbances, and in language paradigms from outside neurology. A systematic examination of the behaviors that were historically incorporated into aphasia classifications, the changes over time in what behaviors were considered important enough to classify, and the context in which these observations took place can serve as the entry point for a critique of current aphasia studies. Part 1 of this three-part series therefore examines the historical roots of contemporary aphasiology with these issues in mind. PMID- 8513407 TI - A reappraisal of localization theory with reference to aphasia. Part 2: Language theories from outside neurology. AB - Part 1 of this series explored various historical writings about aphasia in order to understand the current scope of the field and the prevailing neuroanatomical model. This paper will examine the contexts from which key aphasiologists mentioned in Part 1 wrote, with particular attention to influential language theories from outside neurology. Some biases of the Standard Average European languages used by these authors have shaped aphasia theories indirectly and will also be discussed. This analysis reveals an historical shift in the subject matter of aphasiology, from speech behaviors to "language," defined quite broadly. This shift in subject has serious implications for attempts to localize language in the brain. PMID- 8513408 TI - Thermal stress on chickens in transit. AB - 1. An artificial chicken, 'Gloria', was constructed to simulate heat exchanges of poultry during transport. Tests of the instrument in a wind tunnel showed it to have insulation properties similar to that of a live bird. 2. Gloria accompanied chickens in two types of transport modules, A (enclosed) and B (open). The average temperature difference between inside and outside the loaded vehicles when stationary and in motion were 14.0 and 7.6 for Type A and 8.8 and 6.0 for Type B. Average air movement while vehicles were in motion was 0.5 m/s for Type A and 3.3 m/s for Type B. 3. Measurements of sensible heat loss from Gloria at different temperatures and wind speeds were compared with published estimates of thermoneutral heat production and thermal insulation for well and poorly feathered chickens to estimate the range of thermal stresses likely to be experienced by chickens in transit. 4. The results showed that the combination of circumstances necessary to ensure thermal comfort for birds both at rest and in motion is very rare (e.g. only between 7 and 8 degrees C for well feathered birds in enclosed vehicles). It is, however, possible to ensure thermal comfort over a wide range of ambient air temperatures by appropriate control of air movement within the vehicle whether at rest or in motion. PMID- 8513409 TI - Breed differences in the histochemical properties of the M. pubo-ischio-femoralis pars medialis myofibre of domestic cocks. AB - 1. Histochemical properties of M. pubo-ischio-femoralis pars medialis (PIF muscle) were compared in 7 breeds of cocks. This muscle was largely composed of Type I fibres and their transitional form (Type I tr). Type IIA fibres were observed in the cranial part. 2. The weight and cross-sectional area of the PIF muscle increased with increasing body weight. However, the relative muscle development to body weight differed among the 7 breeds. 3. A quarter of Type I fibres were of the transitional variety in bantam fowls. Conversely, few, if any, Type I tr fibres were observed in the large breeds where the muscle was poorly developed. 4. As the histochemical properties of Type I fibres made an effective response to the different body weights and the relative PIF muscle development among breeds, it was concluded that PIF muscle performed an important function in supporting the body weight and maintaining posture. PMID- 8513410 TI - Effect of warm drinking water on the performance and immunological responses of broiler breeder hens raised at low air temperatures. AB - 1. The effect of warmed drinking water on the performance and immunological responses of broiler breeder hens maintained at low air temperatures (5.0 degrees to 12.9 degrees C) was tested. From 22 weeks of age hens (mean body mass = 2.4 kg) were offered either warm water (27.7 degrees C; WARM; n = 24) or tap water (12.7 degrees C; CONR; n = 24) twice daily for a total time of 2.5 h or tap water ad libitum (CONA; n = 16). Food was restricted for all hens. 2. Daily water intake in the WARM hens (103 ml/kg) was similar to that of the CONR (93 ml/kg) and CONA hens (106 ml/kg). 3. There were no significant differences in either body mass change or egg production among treatment groups. 4. There was no difference among groups in heterophil/lymphocyte ratios. Similarly, there was no difference among groups in either phagocytic activity or wattle index after phytohaemagglutinin (PHA) injection. Total and IgG antibody titres to SRBC tended to be highest in the WARM hens and these titres were significantly higher than in CONR hens 14 d after challenge. PMID- 8513411 TI - Influence of heated vegetable oils and alpha-tocopheryl acetate supplementation on alpha-tocopherol, fatty acids and lipid peroxidation in chicken muscle. AB - 1. Chicks were fed on diets containing fresh, heated or alpha-tocopheryl acetate supplemented heated vegetable oils. The effects on alpha-tocopherol status, and on the fatty acid composition and oxidative stability of thigh and breast muscle were determined. 2. Plasma alpha-tocopherol was significantly correlated with alpha-tocopherol concentrations in thigh and breast muscle. 3. The fatty acid profiles of muscle lipids reflected dietary fatty acid composition. 4. The consumption of heated sunflower and linseed oils reduced alpha-tocopherol status, altered fatty acid composition of muscle lipids and increased susceptibility of muscle to lipid oxidation. 5. Supplementation of diets containing heated oils with alpha-tocopheryl acetate resulted in some alleviation of these effects. 6. The results indicate that caution should be exercised in the use of thermally oxidised oils in poultry diets if undesirable changes in composition and oxidative stability of carcase lipids are to be avoided. PMID- 8513412 TI - Comparative utilisation of sulphur-containing amino acids by genetically lean or fat chickens. AB - 1. Genetically lean (LL) or fat (FL) male chickens were fed from 28 to 47 days of age on 5 experimental diets differing by their methionine+cystine content (5.4, 5.8, 6.2, 6.6 and 7.0 g/kg, respectively). 2. Growth rate of LL chickens was reduced by the lower sulphur-containing amino acid (SAA) concentrations whereas that of FL was not modified. 3. LL chickens exhibited a larger feather protein gain than FL, which was stimulated by SAA intake. 4. SAA retention, when plotted against SAA consumption, was always greater in LL than in FL. 5. Large differences were observed between genotypes for plasma-free amino acids. Lysine, glutamic acid, histidine and serine were found at significantly higher concentrations in LL birds. Branched amino acids, aromatic amino acids, SAA and arginine were found at higher concentrations in FL. No differences were observed for aspartic acid, glycine, alanine and total amino acids. Methionine supplementation decreased free amino acid concentrations, with the exceptions of arginine and leucine. 6. It is concluded that lean chickens require a higher dietary concentration of SAA than FL. This is mainly caused by their lower food consumption and their greater feather synthesis. However, LL use SAA more efficiently than FL. PMID- 8513413 TI - Effects of short-term thyroxine administration during the laying period on egg production and moulting by turkeys. AB - 1. Effects of thyroxine (T4) administration on egg production, moulting and photorefractoriness in laying turkeys were determined. Thyroxine dosages of 0.075 to 2 mg/bird/d were injected IM for periods of either 2 or 3 weeks following 10 weeks of photostimulation. Control groups were administered saline vehicle. 2. Plasma T4 concentrations were increased in a dose dependent manner by T4 administration, while triiodothyronine (T3) was decreased. 3. Egg production and percentage of hens in production were transiently decreased in a dose dependent manner by T4 administration, but returned to levels similar to controls within 4 weeks of T4 treatment termination. Moulting was stimulated in a dose-dependent manner by T4 administration, but was similar to controls after T4 treatment termination. Only dosages of 2 mg/bird/d resulted in cessation of egg production and complete moulting. 4. Results indicate that although short term elevation of plasma T4 causes cessation of egg production and moulting these effects are transient and not indicative of photorefractoriness. PMID- 8513414 TI - Patient newsletters: the debate continues. AB - Producing a patient newsletter is a worthwhile venture if you're doing it for the right reasons. As one component of an overall internal marketing strategy, it demonstrates to patients that you are a concerned caregiver, not only during their visits to your practice but in between those visits. If it's a professional looking publication with quality content and visuals, it will likely be appreciated by your patients. And as you well know, the dental profession is certainly not suffering from a surplus of appreciation. PMID- 8513415 TI - HIV insurance coverage. PMID- 8513416 TI - Electronic imaging in the dental office. PMID- 8513417 TI - Socialized dentistry for children in Saskatchewan its beginning--1974 its demise- 1993. PMID- 8513418 TI - Two-year outcome study of zinc oxide-eugenol root canal treatment for vital primary teeth. PMID- 8513419 TI - Composite resin restoratives revisited. AB - To choose the most suitable composite for the clinical challenge, the clinician must consider a number of issues. This paper examines those issues, as well as how the selected material can best be manipulated to obtain optimum results. It is intended to help the clinician select this material, and to provide information on the clinical relevance of the different compositions and filler sizes of composite materials, proper techniques for light curing--including the effects of light to resin distance and light angulation--and methods that can be used to evaluate the effectiveness of the light-curing unit. The effect of surface finish on wear is also discussed, along with suggestions on proper finishing techniques. PMID- 8513420 TI - Comparison of the dental health status of six-year-old children in Manitoba. AB - The caries rates of six-year-old Manitoba children from a non-fluoridated Northern community were compared with those of a representative group of southern Manitoba children from non-fluoridated areas. All of the surveyed children became eligible for dental treatment coverage under Manitoba Health's Children's Dental Program approximately two months prior to the survey. Access to dental care was equivalent for all children. Screening (data collection) was completed by Manitoba Dental Health staff and was based on standard World Health Organization (WHO) criteria. The initial assessment of the data indicated that the Northern Manitoba children experienced an average of 82 per cent more decay per child than the southern group. Caries treatment requirements in the north were 59 per cent greater than in the south. The southern Manitoba children were almost twice as likely to be caries free than the Northern children. Closer examination of the Northern data, based on a socioeconomic delineation, indicated that the Northern middle- to high-income group experienced 24 per cent more decay per child than the southern group. The Northern middle- to low-income group experienced 124 per cent more decay per child than the southern group. In this study, it was demonstrated that although increased dental caries experience was closely related to geographic location, socioeconomic factors may play an even greater role in dental caries experience. PMID- 8513421 TI - HMGCoA reductase inhibitors. PMID- 8513422 TI - Diabetes and the heart: state of the art in the 1990s. PMID- 8513423 TI - The Alberta Heart Health Survey: methods and results. AB - OBJECTIVE: The Alberta Heart Health Survey is a population-based investigation of cardiovascular disease (CVD) risk factor prevalence and awareness among Albertans 18 to 74 years of age. DESIGN: A stratified, two-stage, replicated probability sample design developed by Statistics Canada was used to select 3437 individuals (2740 were located) from the Alberta Health Care Insurance Plan enrollment list. Trained community health nurses (n = 36) from 13 public health units conducted home interviews (n = 2237, response rate 82%) and subsequent clinic visits (n = 1993) from February to June 1990, using a core protocol common to similar studies conducted in other provinces, as part of the Canadian Heart Health Initiative. SETTING: The home interview collected data on individual and household demographic characteristics, smoking, alcohol consumption, physical activity, treatment and control of high blood pressure and high blood cholesterol, and family history of CVD. Clinic visits included blood collection for analysis of total plasma cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides; weight, height, waist and hip circumference, and two blood pressure measurements. Standardized protocols were used. Lipid analyses were conducted by the Lipid Research Laboratory, University of Toronto. Data management and analysis were conducted at the University of Alberta. MAIN RESULTS: The overall risk factor prevalence estimates were: high blood pressure 14%; smoking 27%; total cholesterol of at least 5.2 mmol/L, 36%; HDL cholesterol less than 0.9 mmol/L, 10%; LDL cholesterol of at least 3.4 mmol/L, 29%; body mass index 25 or more, 51%; sedentary lifestyle 37%. One or more of the three major risk factors (smoking, high blood pressure, high blood cholesterol) occurred in 57% (70% in those with 12 years of education or less). CONCLUSIONS: While the prevalence rates for the major risk factors are among the lowest in Canada, they are unacceptably high. PMID- 8513424 TI - Rating the urgency of coronary angiography: results of an expert panel process. Ontario Coronary Angiography Panel. AB - OBJECTIVE: To rate the urgency of coronary angiography for patients with ischemic heart disease. Ratings were made for patients with varying degrees of symptoms and noninvasive cardiac test results. DESIGN: A panel of 10 cardiologists rated 354 case scenarios which presented varying combinations of clinical factors that may affect urgency. MEASUREMENTS: The case scenarios were rated by each panelist on a waiting time scale consisting of six categories which ranged from the requirement for emergency angiography to a delay of up to three months. A seventh category represented the lack of urgent need for angiography. The contribution of each clinical factor to urgency of coronary angiography was determined. MAIN RESULTS: Symptom class as defined by a modification to the Canadian Cardiovascular Society grading scale for angina pectoris, results of exercise stress tests and results of imaging studies were the major determinants of urgency. In cases of unstable angina, rest electrocardiography is of importance. These factors explained at least 95% of the variance in the case urgency scores. There was agreement by at least five of the panelists on urgency score in 84% of cases. The assigned urgency varied from 6.7, representing no urgent need for angiography, for minimally asymptomatic angina with no positive noninvasive test results, to immediate angiography for cardiogenic shock. Other factors had minimal or negligible effects on urgency. CONCLUSIONS: The urgency of need for coronary angiography was addressed by an explicit method incorporating the judgements of a panel of expert cardiologists, permitting derivation of a scoring system for rating priority of individual patients in the face of waiting lists. These methods illustrate an approach to problems presented by procedure waiting lists. PMID- 8513425 TI - Rapid pulmonary phospholipid accumulation induced by intravenous amiodarone. AB - Amiodarone causes accumulation of phospholipids in lung alveolar cells, and this phospholipidosis invariably is present when amiodarone pulmonary toxicity is recognized. This effect has usually been demonstrated in patients following several months of therapy. The authors report the occurrence of pulmonary phospholipidosis, diagnosed by bronchoalveolar lavage, six days after commencing intravenous amiodarone therapy. PMID- 8513426 TI - Churg-Strauss syndrome presenting with marked eosinophilia and pericardial effusion. AB - The Churg-Strauss syndrome is a rare but treatable clinical entity. Its clinical presentation is thought to be stereotypic but is not. The authors report the first instance of a patient with the Churg-Strauss syndrome with hemodynamically significant pericardial effusion but without concurrent active pulmonary, renal or neurological involvement. Pericardial biopsy was the key to diagnosis and, therefore, therapy. PMID- 8513427 TI - Coronary artery fistula as a complication of percutaneous transluminal coronary angioplasty. AB - A patient underwent successful percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending and the right coronary arteries for worsening angina and was discharged without any apparent complication. Repeat cardiac catheterization, done four weeks later for recurrent angina, showed a coronary artery fistula to the right ventricle at the site of moderately severe subintimal dissection. The patient was managed conservatively. At cardiac catheterization 18 months after the PTCA procedure, there was no evidence of the fistula. PMID- 8513428 TI - Cardioprotection by angiotensin-converting enzyme (ACE) inhibitors. AB - OBJECTIVE: To focus on the cardioprotective role of angiotensin-converting enzyme (ACE) inhibitors in ischemic heart disease and to highlight some of the, as yet, unanswered questions about the relative merits of ACE inhibitors as cardioprotective drugs. DATA SOURCE: This review incorporates the data on this subject published in the available English literature up to June 1990. DATA SELECTION: The source material was analyzed and computed chronologically into two groups: experimental studies and clinical trials. DATA EXTRACTION: ACE inhibitors have gained access to the free world market for a variety of reasons. Their superiority in the management of hypertension and congestive heart failure is being recognized. Furthermore, recent experimental and limited clinical trials strongly indicate a role for ACE inhibitors in limiting myocardial ischemia reperfusion-induced injury. Although the sulphydryl group (SH)-containing ACE inhibitor captopril has been extensively used for most studies, the cardioprotective role of non-SH-containing ACE inhibitors, particularly ramipril and enalapril, recently has been identified. ACE inhibitors reportedly limit infarct size, prevent ventricular remodelling and, more importantly, stabilize the electrical activity of the reperfused heart and prevent the occurrence of reperfusion arrhythmias. Preliminary clinical trials indicate an antianginal role for ACE inhibitors. ACE inhibition has also been reported to improve left ventricular performance in patients with long standing infarcts and ischemic failure. Although pharmacological effects of ACE inhibitors are well known, the mechanism of cardioprotection at the molecular and cellular levels is elusive. The role of ACE inhibitors in myocardial stunning and their free radical scavenging effects are still speculative. Furthermore, the effects of ACE inhibition during global myocardial ischemia-reperfusion are virtually unknown. CONCLUSIONS: The available data strongly indicates a role for ACE inhibitors in limiting myocardial ischemia-reperfusion-induced injury. However, more controlled studies, particularly multicentre clinical trials, are indicated to establish a therapeutic rationale for ACE inhibition in the management of ischemic heart disease. PMID- 8513429 TI - Maximal short-term exercise performance and ion regulation in cystic fibrosis. AB - Controversy exists over whether defects in electrolyte transport exist in erythrocytes from cystic fibrosis (CF) patients. We hypothesized that differences in ion regulation in CF would affect skeletal muscle performance during intense exercise. Seven well-nourished CF patients were compared with seven healthy age matched control subjects. Skeletal muscle performance was assessed during a 30-s sprint on an isokinetic cycle ergometer. Ion regulation was evaluated from arterialized venous blood sampled at rest, at peak exercise, and after 5 min of recovery. There was no difference in sprint performance between the CF (total work, 93.7 +/- 30.02% predicted; endurance, 30.6 +/- 9.93% decline) and control (109.7 +/- 19.48%; 35.6 +/- 14.76%) groups. The changes in plasma and erythrocyte ions and blood gases did not differ between the groups. There was a suggestion that the CF group may have had an inadequate ventilatory response to the metabolic challenge of short-term maximal exercise. The contribution of decreases in the strong ion difference to increases in plasma hydrogen ion concentrations was less in the CF group. This may be due to alterations in ionic regulation in CF, but the influence of inadequate arterialization of the blood samples could not be ruled out. PMID- 8513430 TI - Nucleotide requirement and effects of fatty acids on protein synthesis and degradation in brown adipose tissue mitochondria. AB - The objective of this work was to evaluate whether changes in respiratory status of isolated brown-fat mitochondria influence synthesis and degradation of proteins within the organelles. Mitochondrial protein synthesis is subject to regulation, as a 24-h fast in mice reduced [35S]methionine incorporation without affecting the stability of the newly synthesized proteins. Proteins synthesized in isolated mitochondria were labile and degraded in a process stimulated by ATP. ATP hydrolysis was required within the organelle, as ATP-stimulated protein breakdown was inhibited by atractyloside, an inhibitor of adenine nucleotide transport, and by arsenate and vanadate, which inhibit ATPases. Additions of ATP and ADP were equally effective at reducing mitochondrial oxygen consumption. However, ATP added exogenously was better at supporting protein synthesis and degradation than ATP generated by oxidative phosphorylation when mitochondria were incubated with ADP, substrates, and Pi. GDP also reduced oxygen consumption and stimulated degradation of mitochondrial translation products. Addition of fatty acids in the presence or absence of carnitine-CoA increased mitochondrial respiration but had no effect on protein synthesis or degradation. Addition of carbonyl cyanide m-chlorophenylhydrazone (mCCP) had no effect on ATP-stimulated protein degradation. These results indicate that synthesis and stability of mitochondrial translation products are not significantly influenced by changes in the activity of the uncoupling protein brought about by additions of adenine nucleotides and fatty acids. PMID- 8513431 TI - Intracellular calcium disruption as a secondary event in acetaminophen-induced hepatotoxicity. AB - To examine a role for disturbances in intracellular calcium homeostasis in acetaminophen-induced hepatotoxicity, freshly isolated mouse hepatocytes were incubated with 1.0 mM acetaminophen for 1.5 h to allow for covalent binding and initiation of cell damage. The hepatocytes were then washed and the cells incubated in fresh medium containing either 2.0 mM N-acetylcysteine or 1.5 mM dithiothreitol for the duration of a 4-h incubation period. These agents were used as tools in the elucidation of the biochemical events responsible for acetaminophen-induced cell necrosis. The reduced protein sulfhydryl content, cytosolic [Ca2+], and plasma membrane integrity were quantitated. Acetaminophen produced protein sulfhydryl depletion, an increased cytosolic [Ca2+], and cell injury; however, cytotoxicity preceded the increase in [Ca2+]. Both N acetylcysteine and dithiothreitol restored the acetaminophen-induced protein sulfhydryl loss. Dithiothreitol prevented both further cell injury and an increase in the cytosolic [Ca2+]. However, cell death and a subsequent increase in cytosolic [Ca2+] proceeded unabated following N-acetylcysteine addition. Although both agents restored protein sulfhydryl content, in view of their contrasting ultimate effects on cell viability the role of reduced protein sulfhydryl depletion in acetaminophen-induced hepatic injury requires further investigation. The increase in cytosolic [Ca2+] with acetaminophen alone and with subsequent N-acetylcysteine addition was determined to be a secondary event in cell injury because cytotoxicity occurred by 1.5 h; however, the increase in cytosolic [Ca2+] was not observed until 2.5 h. Additional evidence for changes in cytosolic [Ca2+] as a secondary event was obtained by incubating the hepatocytes with acetaminophen in the presence of fura 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513432 TI - Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats. AB - The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function. PMID- 8513433 TI - General anesthetics inhibit cytochrome P450 monooxygenases and arachidonic acid metabolism. AB - Identification of a specific biomolecular target appropriately sensitive to a wide array of anesthetics has been elusive. At concentrations close to their respective ED50's for anesthesia in man or other species, 18 compounds, differing in potencies up to 66,000 fold, inhibited cytochrome P450 mediated metabolism of aminopyrine, a synthetic substrate, and arachidonic acid (AA), an endogenous substrate, in isolated liver microsomes. There was a highly significant correlation for both substrates between the absolute concentrations required for anesthesia (EC50) and for inhibition of P450 activity (Ki or IC50). The mean Ki/EC50 ratio was 0.97 for inhibition of aminopyrine demethylase. The mean IC50/EC50 ratios were 0.42 and 0.64 for inhibition of two AA-derived products and 2.8 for a third; a mean ratio of 1.4 for inhibition of overall AA metabolism suggests interaction of general anesthetics with a composite of P450 isozymes. The universal cytochrome P450 monooxygenases, in conjunction with other lipid oxygenases (cyclooxygenases and lipoxygenases) participate in the second messenger AA cascade. In nerve cells the sensitivity of these enzymes to hydrophobic neurodepressant drugs may underlie the state of general anesthesia: reversible disruption of intracellular and intercellular signalling without impairment of enzymes vital to cell respiration. PMID- 8513434 TI - Gastrointestinal inflammation: focus on the vascular endothelium. AB - Ischemia of the intestine predominantly affects the small bowel and colon, and may ensue from a variety of causes, ranging from radiation enteritis to the use of drugs that affect the intestinal vasculature. Gut ischemia has historically been thought of as "large-vessel" disease, but microcirculatory pathology and ischemia-reperfusion injury is increasingly being implicated in gut infections and even in chronic idiopathic inflammatory processes involving the gut, such as ulcerative colitis and Crohn's disease. PMID- 8513435 TI - Leukocyte--endothelial cell adhesion induced by ischemia and reperfusion. AB - Reperfusion of ischemic tissues is associated with an enhanced production of inflammatory mediators, increased rolling, adherence, and emigration of leukocytes in postcapillary venules, and vascular protein leakage. There is a growing body of evidence that the leukocyte--endothelial cell interactions are largely responsible for the microvascular dysfunction induced by ischemia- reperfusion. Oxygen radicals, produced by xanthine oxidase and other enzymes, appear to play an important role in initiating and amplifying the inflammatory response elicited by ischemia--reperfusion, while neutrophilic proteases contribute significantly to the injury response. The magnitude of the inflammatory responses observed during ischemia and reperfusion is also influenced by adhesion forces generated by specific glycoproteins expressed on the surface of granulocytes and microvascular endothelium, as well as shear forces that are generated by the movement of blood within the microcirculation. Manipulation of free-radical production, leukocyte--endothelial cell adhesion, and (or) intravascular shear forces provides an effective means for attenuating the deleterious influences of ischemia--reperfusion on the microvasculature. PMID- 8513436 TI - Endothelial adhesion molecules and their role in inflammation. AB - The emigration of leukocytes such as neutrophils into inflammatory sites requires adhesion to the endothelium of small venules. The initial adhesive event is margination characterized by rolling of neutrophils along the luminal surface of the endothelium. Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow. E-selectin is synthesized by endothelial cells following cytokine stimulation, P-selectin is rapidly mobilized from Weibel-Palade bodies to the endothelial cell surface following stimulation with agents such as histamine, and L-selectin is constitutively expressed on the surface of leukocytes. Each selectin functions primarily as a lectin, recognizing carbohydrate structures on the leukocyte or endothelial cell surface. Once the marginated neutrophil forms a stationary adhesion with endothelial cells, it is stimulated by chemotactic factors to downregulate the selectin-based adhesion and upregulate adherence dependent on beta 2-integrins, principally CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1). These adhesion molecules interact with intercellular adhesion molecule 1 (ICAM-1) and possibly other structures on the endothelial cell, and the leukocyte rapidly emigrates into surrounding tissue. Transendothelial migration in vitro is markedly inhibited by monoclonal antibodies against CD18 integrins or ICAM-1. Monoclonal antibodies against the selectins, CD18, CD11a, CD11b, and ICAM-1 have all been shown to significantly reduce the influx of neutrophils into sites of inflammation in various animal models. PMID- 8513437 TI - Polymorphonuclear leukocyte--endothelium interactions: a role for pro inflammatory and anti-inflammatory molecules. AB - The movement of polymorphonuclear leukocytes (PMNs) from the mainstream of blood to the extravascular space is a characteristic feature of the inflammatory response. This process requires that the PMN initially contacts the endothelium, then adheres firmly to the vessel wall, and finely migrates out of the microvasculature. Each of these events requires signals or pro-inflammatory molecules that direct the PMN to the potential site of inflammation. These molecules include histamine, which appears to be of importance in the initial recruitment of PMNs, leukotriene B4, which promotes PMN adhesion, and platelet activating factor, which may contribute to both the adhesion process as well as the migration through the endothelial barrier. Although many other pro inflammatory molecules have been identified, including the cytokines and complement, the three aforementioned molecules are used in this review as paradigms of the varying functions that pro-inflammatory molecules have in the inflammatory process. There is a growing body of evidence that in addition to the many pro-inflammatory agents found in the body there are a number of important anti-inflammatory molecules, including nitric oxide, prostacyclin, and adenosine. Each of these molecules possess important properties that serve to interrupt or protect against the ongoing inflammatory process. The anti-inflammatory potential of these endogenous molecules is discussed. PMID- 8513438 TI - Gastric ulceration: critical events at the neutrophil--endothelium interface. AB - Neutrophil adherence to the vascular endothelium and the subsequent release of oxygen-derived free radicals and proteolytic enzymes has been implicated as a critical event in the pathogenesis of various forms of gastrointestinal ulceration. This paper reviews the evidence that events at the neutrophil endothelium interface are important in the pathogenesis of gastric ulceration induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Endothelial injury occurs within minutes of NSAID administration and appears to be attributable to neutrophil adherence and activation. Neutrophil adherence in response to NSAIDs may occur as a consequence of inhibition of endothelial prostaglandin synthesis, but it appears to involve a lipoxygenase product, such as leukotriene B4. Prevention of neutrophil adherence to the vascular endothelium results in near complete prevention of experimental NSAID gastropathy. Depletion of circulating neutrophils also results in reduced susceptibility to NSAID-induced mucosal injury. As prostaglandins are potent inhibitors of neutrophil adherence and activation, it is possible that the neutrophil--endothelium interface represents one of the most important targets of action of these compounds in terms of their ability to prevent or reduce the severity of NSAID-induced ulceration. PMID- 8513439 TI - XXVIIIth Meeting of the Canadian Congress of Neurological Sciences. Toronto, Ontario, June 16-19, 1993. Abstracts. PMID- 8513440 TI - p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. AB - Pancreatic expression of the p53 tumor suppressor gene was studied in pancreatic adenocarcinomas and chronic pancreatitis. By immunohistochemistry, 16 of 34 (47%) cancers and none of the 24 chronic pancreatitis samples revealed nuclear staining. Sequence analysis indicated that 8 of 24 (33%) cancers were mutated for the p53 gene. Point substitutions occurred at codons 35, 105, 133, 213, 213, 258, and 299. A three base-pair in-frame insertion was identified between codons 261 and 262. None of 8 chronic pancreatitis samples exhibited p53 gene mutations. These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis. PMID- 8513441 TI - c-Ha-Ras mutants with point mutations in Gln-Val-Val region have reduced inhibitory activity toward cathepsin B. AB - Protease-inhibitory activity of recombinant Ha-ras gene products (Ras) toward papain and cathepsins B and L was investigated. v-Ha-Ras showed more potent inhibitory activity toward cathepsin B as compared with c-Ha-Ras. We have also investigated protease-inhibitory activity of c-Ha-Ras mutants with point mutations in amino acids between positions 23 and 50. Inhibitory activity of Ras toward papain and cathepsin L was not largely altered among mutants. However, the inhibitory activity toward cathepsin B was significantly impaired by a mutation at position 43, 44, 45 or 48. These results suggest that 43Gln-Val-Val sequence plays an important role at least to inhibit cathepsin B. PMID- 8513443 TI - Purification and analysis of a human sarcoma associated antigen. AB - S1, a heterophile antigen present on human sarcoma cell lines in culture, has been previously defined by this laboratory [1,2]. This antigen is also present in guinea-pig kidney. Purification of the antigen to homogeneity has now been achieved by a combination of ammonium sulfate fractionation, DEAE-cellulose, sephadex, high pressure liquid chromotography and affinity chromotography. S1 is a monomeric protein of 70,000 Da, as indicated by the presence of a single band on SDS-PAGE. Amino acid analysis demonstrates the prevalence of glycine, lysine and glutamic acid. Aspartic acid was found to be the N-terminal residue with further sequence of glycine-valine-alanine-glutamic acid (gly-val-ala-glut). PMID- 8513442 TI - Inhibition of benzoyl peroxide-induced tumor promotion and progression by copper(II)(3,5-diisopropylsalicylate)2. AB - The ability of a biomimetic superoxide dismutase agent, copper(II)(3,5 diisopropylsalicylate)2 (CuDIPS), to modulate benzoyl peroxide (BzPo)-induced tumor promotion and progression in mouse skin multistage carcinogenesis was evaluated. The results showed a significant inhibition of tumor incidence by CuDIPS pretreatment during promotion-progression. Different types of tumors were developed: papillomas, keratoacanthomas and squamous cell carcinomas. There was a significant increase in the keratoacanthoma-papilloma ratio when the period of treatment with BzPo was prolonged, which was inhibited by CuDIPS pretreatment. CuDIPS induced a significant inhibition of malignant conversion. Our results suggest that reactive oxygen species could be important in BzPo-induced promotion and progression. PMID- 8513444 TI - Potentiation of butyrate-induced differentiation in human colon tumor cells by deoxycholate. AB - Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation. PMID- 8513445 TI - Serum cross-reactive thymosin alpha 1 levels in rats during induction of mammary carcinoma with 7,12-dimethylbenz[a]anthracene: short- and long-term effects. AB - The levels of serum cross-reactive thymosin alpha 1 (CRT alpha 1) were measured at various time intervals during the course of development of mammary tumors in female Sprague-Dawley rats intubated with 7,12-dimethylbenz[a]-anthracene (DMBA; 10 mg/rat). Matched control rats were also tested simultaneously. An increase in CRT alpha 1 in DMBA-treated animals was observed within 2 h of DMBA treatment. Thereafter the levels of CRT alpha 1 in the serum of the DMBA-treated rats remained elevated for another 3 weeks prior to declining to control levels. Levels remained stationary until an increase in serum CRT alpha 1 was observed at 9-11 weeks post-DMBA treatment. This correlated with the time when mammary tumors were either palpable or observed. Levels of CRT alpha 1 fell at 13 weeks but remained slightly elevated until sacrifice due to tumor burden at 18 weeks. PMID- 8513446 TI - In vitro effects of natural plant polyphenols on the proliferation of normal and abnormal human lymphocytes and their secretions of interleukin-2. AB - The growth of two human lymphoid tissue derived cell lines, IM-9 and Molt-4 cells together with normal lymphocytes was studied in the presence of several plant natural products. Amongst the 11 test compounds studied, the flavonoids (fustin, taxifolin, phloretin) and the polyphenol tannic acid were potent inhibitors. At concentrations ranging from 10-50 microM they exerted varying degrees of inhibition on Molt-4 cell and normal lymphocyte cell proliferation but not on the non-malignant (IM-9) cells. The order of potency was tannic acid > phloretin > taxifolin > fustin. The IL-2 level was also enhanced in the Molt-4 but inhibited in normal lymphocytes. However, its level remained unchanged in the IM-9 cells. The amount of IL-2 secreted could be directly correlated to the percentage cell growth inhibition for only Molt-4 cells. Interestingly, our findings suggest the possibility of exploiting the natural plant polyphenols for their possible use in the treatment of lymphocyte malignancy. PMID- 8513447 TI - Effect of exogenous heparin on anchorage-independent growth of fibroblasts induced by transforming cytokines. AB - Heparin at concentrations below 100 micrograms/ml stimulated anchorage independent growth of NRK 49F (normal rat kidney fibroblasts, American type culture collection) rat fibroblasts at suboptimal cytokine concentrations but inhibited it at higher heparin concentrations regardless of the cytokine concentration. Heparin did not stimulate growth above that seen at optimal cytokine concentrations, suggesting that it alters the cellular response to the cytokines. These data suggest natural protein-glycosaminoglycan interactions play a role in modulating or mediating the actions of transforming cytokines and suggest they may play a role in acquisition of the transformed phenotype. PMID- 8513448 TI - Tumoricidal effect of human macrophage-colony-stimulating factor against human ovarian-carcinoma-bearing athymic mice and its therapeutic effect when combined with cisplatin. AB - The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect. PMID- 8513449 TI - Clonal analysis of in vivo activated CD8+ cytotoxic T lymphocytes from a melanoma patient responsive to active specific immunotherapy. AB - To study in vivo activated cytolytic T cells, CD8+ T cells clones were isolated from a melanoma patient (HLA A2, A11) treated with active specific immunotherapy for 5 years. CD8+ T lymphocytes, purified by fluorescence-activated cell sorting, were cloned directly from the peripheral blood without antigen-presenting cells in the presence of irradiated autologous melanoma cells and recombinant interleukin-2 (IL-2) and IL-4. These conditions were inhibitory to de novo in vitro immunization. Of the 28 cytolytic CD8+ T cell clones, 21 lysed the autologous melanoma cell line (M7) but not the autologous lymphoblastoid cell line (LCL-7) nor the two melanoma cell line, M1 (HLA A28) and M2 (HLA A28, A31), used to immunize the patient. The remaining 7 clones were also melanoma-specific, although their reactivities were broader, lysing several melanoma cell lines but not HLA-matched lymphoblastoid cells. Eight clones from the first group, ostensibly self-MHC-restricted, were expanded for further analysis. All expressed cluster determinants characteristic of mature, activated T cells, but not those of thymocytes, naive T cells, B cells or natural killer (NK) cells. They also expressed CD13, a myeloid marker. Of the 8 clones, 3 expressed both CD4 and CD8, but dual expression was not correlated with specificity of lysis. Two CD8+ and 2 CD4+ CD8+ clones were specific for the autologous melanoma cells, the other 4 were also reactive against other HLA-A2-positive melanomas. Cytotoxicity for both singly and doubly positive clones was restricted by HLA class I but not class II antigens. Analysis of the RNA expression of the T cell receptor (TCR) V alpha and V beta gene segments revealed heterogeneous usage by the A2-restricted clones and, perhaps, also by the broadly melanoma-specific clones. Apparent TCR restricted usage was noted for the self-MHC-restricted clones; 2 of the 4 expressed the V alpha 17/V beta 7 dimer. Since the T cell clones were derived from separate precursors of circulating cytotoxic T lymphocytes (CTL), the V alpha 17/V beta 7 TCR was well represented in the peripheral blood lymphocytes of this patient. In summary, we show that melanoma cells presented their own antigens to stimulate the proliferation of melanoma-reactive CD8+ CTL. CTL with a range of melanoma specificities and different TCR alpha beta dimers were encountered in this patient, perhaps as a result of hyperimmunization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513450 TI - The effects of interleukin-1 therapy on peripheral blood granulocyte function in humans. AB - During a phase I trial of interleukin-1 alpha (IL-1 alpha) in patients with ovarian carcinomas, the effects of this treatment on blood granulocyte respiratory burst and locomotive responses were examined. Differences in baseline granulocyte function in patients as well as dose-related effects of IL-1 alpha treatment were observed. Patients enrolled early in the trial (low-dose patients) had significantly lower locomotive responses before treatment than their paired controls; these low responses normalized after 5 days of continuous-infusion IL-1 alpha treatment. Patients enrolled later (high-dose patients) had normal locomotive responses before treatment and IL-1 alpha treatment was associated with suppression of responses to selected stimuli at the end of treatment. Pretreatment respiratory burst responses in both low- and high-dose patient groups were essentially normal, but the rates of granulocyte H2O2 production following phorbol myristate acetate stimulation became significantly less than control values at the end of treatment. In vitro exposure of either patient or control cells to 150 U/ml IL-1 alpha did not alter their locomotive or respiratory burst responses, suggesting the observed in vivo effects were not mediated directly by IL-1 alpha. Treatment with IL-1 alpha is associated with changes in ex vivo granulocyte function that are related to the IL-1 alpha dose. Treatment with low doses of IL-1 alpha may provide a means of normalizing abnormal polymorphonuclear leukocyte function in some patients with ovarian malignancies. PMID- 8513451 TI - Clonal analysis of peripheral blood lymphocytes from three patients with advanced neuroblastoma receiving recombinant interleukin-2 and interferon alpha. AB - In this study we have investigated, at the population and the clonal levels, the immunophenotypes and the non-specific cytotoxic functions of peripheral blood lymphocytes from three stage IV neuroblastoma patients receiving treatment with recombinant interleukin-2 (IL-2) and interferon alpha (IFN alpha). Both IL-2 alone and the combination of IL-2 and IFN alpha caused an in vivo expansion of CD56+, CD3- NK cells most of which expressed the p75 molecule, i.e. the beta chain of the IL-2 receptor. Peripheral blood mononuclear cells (PBMC), drawn after treatment, displayed an increased NK activity, but no lymphokine-activated killer (LAK) activity. However, the subsequent in vitro culture of PBMC with high dose IL-2 induced the generation of a potent LAK activity, which was mediated by an expanded population of CD3+, CD8+ T cells. Finally lymphocytes that had been isolated after cytokine therapy were cloned, in the presence of low-dose phytohemagglutin, immediately or following culture with IL-2. Clones derived from LAK cells expanded in vitro had predominantly a CD3+, CD8+ immunophenotype, whereas those raised from freshly separated lymphocytes were either CD3+, CD4+ or CD3+, CD8+ in equal proportions. Most of the above clones were poorly or not at all cytolytic against NK-sensitive or NK-resistant targets. In contrast, the few NK clones obtained (CD3-, CD56+) lysed all targets with high efficiency. PMID- 8513452 TI - Generation of cytotoxic T lymphocytes from peripheral blood of leukaemic patients. AB - Peripheral blood mononuclear cells from 13 patients with acute leukaemia were used to establish long-term interleukin-2-dependent cytotoxic T lymphocytes. Cells were grown in RPMI medium containing interleukin-2 (IL-2, 100 U/ml) and 2.5% conditioned medium prepared by activating normal lymphocytes with phytohaemagglutinin. Proliferation of IL-2-dependent CD3-positive lymphocytes was seen in 1 of 2 acute lymphocytic leukaemia cases (ALL), 1 of 4 acute myelogenous leukaemia cases (AML) (M1) and 8 of 8 more differentiated AML. In 2 cases with detectable leukaemic cell markers (1 ALL and 1 AML) passageable cells were developed, that expressed normal T cell phenotypes (namely CD3, CD4 and CD8) at the expense of leukaemic cells. In 1 of 2 cases, long-term IL-2-cultured cells showed specific cytotoxic activity against autologous leukemic cells. The percentage killing against autologous and two allogeneic target cell lines at a 50/1 effector/target (E/T) ratio was 42%, 9% and 19% respectively. Similarly the cytotoxic activity of IL-2 activated from 4 different individuals against conventional tumour targets K562 and Daudi at a ratio of 50/1 was 29%-68% (median = 55%) and 34%-78% (median = 61%) respectively. It was also found that this killing potential of the activated cells was maintained for as long as culture was continued (median 23 days, range 17-75 days). The mechanism(s) of T cell proliferation at the expense of leukaemic blast cells in the case of a minority of leukaemic patients and the possible clinical therapeutic potential of these cells following in vitro IL-2 activation deserve further investigation. PMID- 8513453 TI - Recombinant interferon alpha-2a in combination with dacarbazine in the treatment of metastatic malignant melanoma: analysis of long-term responding patients. AB - Thirty-four evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and analyze the long term therapeutic efficacy of recombinant interferon (rIFN) alpha-2a and dacarbazine. Patients received 14 days of daily subcutaneous r-IFN alpha-2a (3 x 10(6) IU/day), followed by 9 x 10(6) IU on alternate days, as long as objective response lasted, in combination with i.v. dacarbazine started on day 7 (400 mg/m2) and repeated every 21 days (dacarbazine doses were escalated to 800 mg/m2). In 11 patients, 6 complete (17.6%) and 5 partial (14.7%) responses were seen, with an overall response rate of 32.3% (95% confidence interval: 16%-48%). The median survival time of the responding patients was significantly better than that of patients with progressive disease (P = 0.01) and the median response time of the patients showing complete response was longer than that of the partially responding patients (14 and 7 months respectively, P = 0.06). PMID- 8513454 TI - Immunization with mutagen-treated (tum-) cells causes rejection of nonimmunogenic rat glioma isografts. AB - The ethyl-N-nitrosourea-induced rat glioma N32 was treated with the mutagenic compound N-methyl-N'-nitro-N-nitrosoguanidine and the surviving cells cloned by limited dilution. Out of 20 clones tested 8 did not produce tumors subcutaneously even after challenge doses 3 log units above the minimal tumor dose for N32. All of 5 clones grew in a retarded manner intracerebrally but produced tumors in some animals. Preimmunizations with three of the rejected clones (tum-) gave protection against subcutaneous and intracerebral isografts of the unmutated N32. This effect could be enhanced if the cells used for immunizations were pretreated with interferon gamma (IFN gamma) for 48 h. If immunizations were started subsequent to challenge, only immunization with one of two tested tum- clones pretreated with IFN gamma induced significant rejection against intracerebral N32 isografts. Both N32 and its tum- clones were MHC class I positive and MHC class II negative. IFN gamma treatment enhanced the MHC class I expression with 20%-90% on the tum- clones and with 40% on N32. MHC class II expression could be induced on N32 cells after 7 days of IFN gamma treatment but not on any of the tum- clones tested. We conclude that the enhancing effect of IFN gamma treatment on tumor isograft rejection may depend on up-regulation of MHC class I but not of MHC class II. This investigation demonstrates that it is possible to induce rejection of weakly immunogenic intracerebral brain tumors by immunization with selected highly immunogenic tumor cell mutants. In conjunction with relevant cytokines, the cross-protective effect of these tum- variants might be further enhanced and serve as a model for immunotherapy against malignant human brain tumors. PMID- 8513456 TI - Focused microbiologic surveillance by specific hospital unit: practical application and clinical utility. AB - Focused microbiologic surveillance by specific hospital intensive care units (ICUs) revealed important differences in the occurrence of pathogens among units and at different times. Moreover, there were striking differences between the antibiogram summaries from certain ICUs and those from the hospital as a whole. Accordingly, an ongoing focused microbiologic surveillance was conducted for hospital ICUs to define unit-specific problems more clearly. To apply these data practically, results of focused surveillance were given to the ICU medical directors. The directors were able to institute unit-specific modifications of antimicrobial usage based upon the prevalent pathogens and their susceptibility patterns within each unit. After 1 year of this approach, the susceptibility patterns of Pseudomonas aeruginosa to imipenem and other antipseudomonal beta lactam agents were improved in a number of ICUs that had previously noted resistance problems of several years' duration. Susceptibility of P aeruginosa was markedly improved in the medical ICU. The susceptibility patterns of Enterobacter cloacae were less affected, if at all. A review of antimicrobial use revealed that the use of most antipseudomonal agents in the medical ICU had decreased by approximately 50% or more. It is concluded that modification of antimicrobial use in ICUs based on focused microbiologic surveillance is a promising way to detect and minimize problems with resistance. PMID- 8513455 TI - Locoregional therapy with polyethylene-glycol-modified interleukin-2 of an intradermally growing hepatocellular carcinoma in the guinea pig induces T-cell mediated antitumor activity. AB - Therapy with repeated intratumoral and perilymphatic administration of relatively low doses of polyethylene-glycol(PEG)-modified interleukin-2 (IL-2) in the syngeneic guinea pig line 10 (L10) hepatocarcinoma results in significant local tumor growth inhibition and a delay in development of regional lymph node metastases of more than 3 weeks when compared to controls. Occasionally animals are cured of tumor. The mechanism of this antitumor activity was studied. The antitumor activity of locoregionally administered PEG-IL-2 was abrogated by pretreatment with polyclonal anti-thymocyte serum, indicating that the observed tumor growth inhibition was a T-cell-mediated phenomenon. Besides the locoregional tumor growth inhibition, a systemic effect was recorded as the growth of a second tumor cell inoculum at the contralateral side was inhibited as well. Furthermore, those animals cured after PEG-IL-2 therapy developed specific immunity against the L10 tumor and this immunity could be transferred to naive animals by spleen cells. Immunohistological observations of the tumor site revealed a slight increase of helper and cytotoxic T cell subpopulations after PEG-IL-2 therapy. More pronounced, however, was the rise in number of eosinophilic granulocytes present in the stroma surrounding the tumor cells. Involvement of cytotoxic cells in the antitumor effects of PEG-IL-2 could not be demonstrated: regional lymph node cells and spleen cells obtained immediately after therapy (day 15) or on day 21 showed no cytotoxic activity in vitro against L10, K562, Daudi and line 1 (L1) target cells. In conclusion, locoregional therapy with PEG-IL-2 induced a a systemic T-cell-mediated antitumor response. As no cytotoxic T cell activity was measured, however, the underlying mechanism is most likely a T-helper response. Eosinophils at the tumor site may be tumoricidal but further experiments must reveal the role of these cells in the PEG-IL-2 induced tumor regression. PMID- 8513457 TI - The clinical relevance of Enterobacter infections. AB - An 18-month prospective study of Enterobacter bacteremia was conducted in 129 patients. The results indicated that (1) emergence of resistance was more frequent during treatment with third-generation cephalosporins than with other antibiotics; (2) the addition of an aminoglycoside to the cephalosporin did not prevent emergence of resistance; (3) previous treatment with cephalosporins was associated with bacteremia caused by multiresistant Enterobacter species; and (4) infection with multiresistant Enterobacter species was associated with a higher mortality than infection with susceptible strains. It is concluded that avoidance of third-generation cephalosporins for surgical prophylaxis and therapy in patients in whom Enterobacter infections are suspected or proven should lower the prevalence of Enterobacter bacteremias and mortality and prevent the emergence of multiresistance. PMID- 8513458 TI - The results of a targeted pharmacy intervention program. AB - Increasing resistance to ceftazidime and some other beta-lactam antibiotics developed among Enterobacter species after use of ceftazidime increased at a 500 bed community teaching hospital. Severe restrictions on the use of ceftazidime were imposed by pharmacy intervention. For empiric therapy of severe infections, a combination of tobramycin plus piperacillin was most frequently substituted for ceftazidime. Susceptibility patterns of Enterobacter returned to baseline within 3 months after active intervention reduced use of ceftazidime by 98% of its peak. There was no development of enhanced resistance to tobramycin or piperacillin or to other antibiotics on the formulary. It is concluded that active pharmacy intervention resulted in reversion of susceptibility of Enterobacter species to baseline for ceftazidime and the other beta-lactam antibiotics (ie, aztreonam, cefotaxime, ceftriaxone, mezlocillin, and piperacillin) for which covariance (ie, parallel decline of organisms' sensitivities) or cross-resistance had developed. PMID- 8513459 TI - Controlling the costs of antibiotic resistance. AB - Excessive and inappropriate use of antibiotics in hospitals contributes to the development of antibiotic resistance and to increased hospital costs. Denver's three major teaching hospitals have developed a multifaceted approach that has curbed inappropriate antibiotic prescribing and reduced costs for antibiotic purchases. A joint antibiotic-use committee with representatives from each hospital's pharmacy and therapeutics committee developed a single antibiotic formulary for systemically active antibacterial agents, based on simplicity, clinical efficacy, previous use patterns, local resistance patterns, and relative cost. This formulary includes primary agents, ordered at the prescriber's discretion; secondary agents, ordered only for an approved condition; and restricted agents, which had been used excessively or inappropriately in the past, and are now dispensed only after consultation with infectious disease specialists. A computerized antibiotic order-entry program at the Denver V.A. Medical Center requires all physicians to enter antibiotic requests through a centralized computer system. Drug utilization is evaluated using data collected from the computer data base and in vitro data from the microbiology laboratory. In addition, appropriate antibiotic prescribing and infection control practices are taught in an education program for physicians, nurses, and other health care workers. PMID- 8513460 TI - Antibiotic cost control measures in a hospital pharmacy. AB - Faced with rising drug costs and an increase in type-1 beta-lactamase resistance, hospitals have been looking for ways to contain antibiotic costs while continuing to provide quality medical care. The hospital pharmacy at Montefiore Medical Center, Moses Division, has developed a number of programs aimed at identifying antibiotic prescribing trends and minimizing costs. An antimicrobial susceptibility cascade reporting (ASCR) system is used to consolidate and target antimicrobial susceptibility information available to the staff physicians. All antibiotics are tested in the microbiology laboratory for susceptibility; however, physicians receive susceptibility reports only for the more cost effective, conventional antibiotics. Broader-spectrum, more powerful, and usually more expensive antibiotics are not reported with the ASCR system unless resistance to the more cost-effective antibiotics is noted. Two other reforms initiated are expansion of the pharmacy-based intravenous additive program to include antibiotics and the implementation of a drug therapy enhancement program authorizing automatic conversion by the pharmacist of targeted drug regimens to more clinically rational, cost-effective regimens. PMID- 8513461 TI - Use of pharmacodynamic concepts in developing a cost-effective dosing method for piperacillin. AB - Because they were almost always used in combination with an aminoglycoside, piperacillin and mezlocillin were considered therapeutic alternatives at Hartford Hospital, a 900-bed teaching facility. To determine an appropriate comparative dose, the bactericidal activities of 5 gm of mezlocillin and 4 gm and 3 gm of piperacillin were compared. The results demonstrated that 4 gm of piperacillin possessed stronger bactericidal activity than either 3 gm of piperacillin or 5 gm of mezlocillin. Hartford Hospital has since approved an antibiotic management program using 4 gm of piperacillin every 8 hours, thereby reducing the daily cost of antibiotic therapy. The modified program offers the hospital measurable cost savings without jeopardizing the quality of care. PMID- 8513462 TI - [New views on the psychiatric needs of children]. AB - The problem of basic psychic needs of children was introduced into the world literature in particular in association with findings on psychic deprivation which is as a rule defined as the consequence of inadequate satisfaction of psychic needs during critical periods of development. In the submitted paper the author presents some results assembled in four relatively new and mutually close branches of psychology--biology of behaviour, prenatal and perinatal psychology, ethological psychology and biodromal psychology. The findings agree as regards the basic importance of psychological "acceptance" of the child by his parents (or possibly by other people holding their place). The decisive need of children in early development stages is the need of security and safety. PMID- 8513463 TI - [Hospital productivity and methods of evaluating utilization of beds]. AB - The authors define the hospital (or departmental) productivity the criteria of which are the use of the hospital capacity: the average length of stay, the occupancy ratio, the turnover interval and the turnover. The authors describe the construction of a nomogram for the graphic evaluation of the position of all four indicators. They submit a formula for calculation of the global "index of hospital productivity". They consider the possibility to increase hospital productivity in particular by reducing the length of stay and turnover interval. They draw attention to the influence of external circumstances on hospitalization and the necessity to evaluate indicators of productivity in association with efficiency, effectivity and quality of hospital care. PMID- 8513464 TI - [Activity and inactivity in old age]. AB - The most important characteristic of old age is quality of life. With the latter various forms of activities (psychosocial and physical) are associated. Activities in elderly and old people are influenced by many factors, the most important ones being the social atmosphere (social perception of old age), the personality of the ageing and old person, his health status and economic security. To a considerable extent everybody is responsible for his own programme of active old age. Support of his individual efforts is, however, essential. PMID- 8513465 TI - [Graft rejection after changing from cyclosporin A therapy to conventional treatment in kidney transplant patients]. AB - Hundred and twenty live patients after the first transplantation of the kidney from a decreased donor with satisfactory graft function, treated with cyclosporine A combined with prednisone or combined with prednisone or combined with prednisone and azathioprine were divided into three groups: A--20 patients changed during the 6th-9th month after transplantation to conventional azathioprine-prednisone treatment. B--68 patients switched to this treatment during the 10h-15th month following transplantation. K--37 patients who were not switched to other treatment during the mentioned period. Within 3 months after the switched rejection develop in 21% of the patients in group A and 20% patients in group B. The incidence of rejections during a comparable period in group K was significantly lower (3%), as compared with group A and insignificantly lower (14%), as compared with group B. The majority of rejections was documented by biopsy but no morphological difference was found between rejections which developed in patients switched and not switched to other treatment. It was striking that there was a difference, though insignificant, in the sensitivity of rejections to antirejection treatment with methylprednisolone after switch to a different preparation: in group A 25%, in group B 37% and in group K 80%. Patients in group A with rejection after the switch had developed a rejection even before the switch significantly more frequently (in 75%) than in group B (in 7%) and these rejections led significantly more frequently to loss of the graft. PMID- 8513466 TI - [Glucose utilization and risk of hyperglycemia during simultaneous administration of branched-chain amino acids and fat emulsions in healthy persons]. AB - In order to evaluate the effect of substrate competition on glucose utilization, we studied 8 healthy volunteers under three different conditions: 1. Hyperinsulinemic (75 a 550 microU/ml) euglycemic (5 mmol/1) clamp (HEC). 2. HEC with Nutramin VLI infusion given at a rate of 2 ml/kg.h. 3. HEC with infusion of Nutramin VLI (2 ml/kg.h) and Intralipid (0.15 g of fat/kg.h). Glucose utilization was evaluated as the glucose disposal rate during HEC. We have found, that Nutramin VLI given alone or with Intralipid does not significantly decrease glucose utilization at insulinemia of about 75 and 550 microU/ml. We conclude that simultaneous administration of substrates during parenteral nutrition at standard rates does not raise the risk of hyperglycemia in healthy men. PMID- 8513468 TI - [The 6th World No-Tobacco Day]. PMID- 8513467 TI - [Duolip Forte--experience during a 6-month period of administration]. AB - Duolip forte (ethophylline clofibrate, tablets a 500 mg) produced by Merckle Austria was administered to 20 patients with different types of hyperlipoproteinaemia for a 6-month period in amounts of 500 mg/day. Before onset of treatment and during treatment the patients adhered to a defined hypolipidaemic diet. The total cholesterol level during administration increased from 7.71 +/- 1.71 mmol/l to 8.23 +/- 1.34 mmol/l (p = 0.05). The LDL cholesterol level rose from 4.93 +/- 1.70 mmol/l to 5.53 +/- 1.34 mmol/l (n.s.). Apolipoprotein B declined from 1.99 +/- 0.39 g/l to 1.80 +/- 0.30 g/l (n.s.). HDL cholesterol rose from 1.09 +/- 0.32 mmol/l to 1.53 +/- 0.56 mmol/l (p = 0.01). The triglyceride level declined from 5.71 +/- 5.60 mmol/1 to 3.72 +/- 4.32 mmol/1 (n.s.). The lipid metabolism parameters were evaluated already after three months of Duolip treatment but the values did not differ significantly from values assessed after 6 months of administration; therefore only the final values are given. In the course of six months of Duolip administration the body weight of the patients did not change and no serious side-effects were observed which would call for discontinuation of treatment. Duolip forte is evaluated as a safe, but as compared with other available drugs of the clofibrate series, less effective hypolipidaemic agent. PMID- 8513469 TI - [The views of UNICEF on the changing world situation and on permanent goals in 1992]. PMID- 8513470 TI - [What is Hodgkin's disease?]. AB - The article summarizes contemporary views on the aetiology, pathogenesis, therapy and prognosis of Hodgkin's disease. The author emphasizes the necessity of intensive search for the origin of malignant cells. From the therapeutic aspect the necessity of team work and the use of a data base is emphasized which facilitates adaptation of treatment to individual patients, depending on prognostic factors. PMID- 8513471 TI - [The present status of therapeutic possibilities in malignant lymphomas]. AB - The therapeutic strategy in the treatment of malignant lymphomas changed somewhat in recent years. In Hodgkin's disease except for exceptional cases (mediastinal involvement) either radiotherapy alone is used or more frequently chemotherapy alone. Optimal treatment is a chemotherapeutic combination of four drugs (MOPP or ABVD). In low grade malignancy non-Hodgkin lymphomas so far cytostatic monotherapy is still the standard treatment, the assumed curative effect of an aggressive combined chemotherapy is being tested. As to new cytostatics, attention is drawn to fludarabine phosphate. In high-grade malignancy non-Hodgkin lymphomas chemotherapy may have a curative effect if the correct principles of its administration are respected, in particular adequate dose intensity in the initial cycles. This demand is met by third generation combinations. The author mentions also contemporary therapeutic possibilities of resistant forms and draws attention to problems of treatment of relapses in Hodgkin's disease and in non Hodgkin lymphomas. PMID- 8513472 TI - [Prognostic factors and their importance in the modification of therapeutic approaches in patients with Hodgkin's disease]. AB - A prognostic study was performed in a group of 236 long-term followed patients. Eleven factors in total were included into a multivariate analysis--they were global, clinical and therapeutical factors. For complete remission, clinical stage, age at the time of diagnosis and size of affliction of mediastinum are important. Signs of poor prognosis for complete remission are "bulky" mediastinal disease, male sex and absence or reduction of chemotherapy in primary treatment. Prognostic factors as to the total survival are age at the time of diagnosis, clinical stage, total number and size of afflicted lymphatic areas and absence or reduction of chemotherapy in primary treatment. Emphasis is laid upon evaluation of the amount of individual risk to adjust therapeutic procedures to every individual patient. PMID- 8513473 TI - [Causes of death in patients with Hodgkin's disease]. AB - The authors analyze the causes of death of 52 patients from a group comprising 236 patients with Hodgkin's disease. From 51 patients 16 died within one year, with a single exception. All were in clinical stage III-IV (at the time of diagnosis). Within 5 years 40 patients died incl. 4 who the time of diagnosis belonged to clinical stage II. After more than 5 years following establishment of the diagnosis 12 patients died. Of these at the time of the diagnosis 8 were in clinical stage II, 3 in clinical stage III and one patient in clinical stage IV. In the first clinical stage and according to histological classification 10 patients survive, in clinical stage II 93 patients, in clinical stage III 105 patients and 28 patients in clinical stage IV. The mortality rate increases with the advancing clinical stage. Causes of death: progression of the basic disease in 63%, intercurrent infectious diseases in 25%, inhibition of bone marrow in 6%, same percentage for development of secondary neoplasms. The lowest mortality rate was recorded in patients treated by a combination of actino- and chemotherapy (11%), as compared with 23% treated by actinotherapy only and 41% treated by chemotherapy only. PMID- 8513474 TI - [Ratios of surface markers (CD) on peripheral blood lymphocytes in the working age Czech population]. AB - The authors present an account of lymphocytic CD signs in adult men (mean age 34 years) and women (mean age 29 years) of the Czech population. Mean values and standard deviations (s.d.) are given for men/women: CD2: 79.6% (6.6)/86.4% (5.3), CD 3: 71.5% (7.4)/81.1% (7.4), CD4: 42.4% (6.3)/48.4% (8.5), %CD45RA+ v CD4+: 41.7% (14.1)/47.3% (13.9), CD5: 69.5% (7.0)/76.00% (6.5), CD8: 33.9% (9.3)/29.8% (6.8). CD10: 1.9% (1.3)/2.5% (1.6), CD11c: 8.3% (4.7)/10.9% (4.4), CD16: 8.3% (3.8)/4.4% (2.3), CD19: 11.5% (4.0)/8.8% (3.2), CD20: 14.7% (4.7)/11.3%, CD22: 10.6% (9.2)/8.9% (3.5), CD45RA: 56.7% (7.6)/61.7% (7.8), CD56: 15.1% (5.7)/16.0% (6.5), CD57: 13.7% (7.9)/8.5% (6.3), CD71: 1.9% (1.3)/3.5% (1.7) a HLA DR: 22.1% (6.4)/19.6% (7.1), DP: 16.3% (7.1)/13.5% (4.9), DQ: 10.9% (5.8)/7.2% (3.2), BJK: 2.6% (2.2)/2.1% (1.1), BJL: 1.8% (1.2)/2.1% (1.3), ratio CD4/CD8 1.35 (0.49)/1.75 (0.69). The examination were made on an apparatus FACScan (Becton Dickinson). PMID- 8513475 TI - [Documentation for the VZP no longer needs to be frightening]. PMID- 8513476 TI - Microtubule-associated distribution of specific granules and secretion of atrial natriuretic factor in primary cultures of rat cardiomyocytes. AB - A close spatial relationship between specific granules containing atrial natriuretic factor (ANF) and microtubules was demonstrated in primary cultures of neonatal rat cardiac myocytes. For the detection of specific granules and microtubules, the myocytes were double immunolabeled with antibodies against alpha-ANF and beta-tubulin and examined by conventional fluorescence or laser scanning confocal microscopy. In addition, the ultrastructural distribution of specific granules was demonstrated by electron microscopy. In the atrial myocytes, ANF was stored in numerous specific granules that were mainly localized in the perinuclear sarcoplasm. In the ventricular myocytes, however, a minority of the cells (10%) exhibited limited ANF immunoreactivity after 4 days in culture. Microtubules were present throughout the sarcoplasm of the myocytes. They were most densely packed in the perinuclear regions. Depolymerization of the microtubules with nocodazole was followed by dispersal of ANF immunostaining both in the atrial myocytes and in the ventricular myocytes exhibiting ANF immunoreactivity. When the microtubules were allowed to recover, the perinuclear distribution of specific granules, as seen in non-treated myocytes, reappeared. Measurements of secreted immunoreactive ANF by radioimmunoassay revealed that the secretion of ANF from atrial myocytes into the medium was significantly reduced following nocodazole treatment, whereas a similar decrease in secretion from ventricular myocytes was not observed. These findings indicate that ANF containing specific granules are closely associated with microtubules within the myocytes. It is suggested that secretion of ANF from the atrial myocytes, in contrast to the ventricular myocytes, is microtubule-dependent. PMID- 8513477 TI - Endothelial cell connecting filaments anchor endothelial cells to the subjacent elastic lamina in the developing aortic intima of the mouse. AB - The ultrastructural association of endothelial cells with the subjacent elastic lamina was investigated in the developing mouse aorta by electron microscopy. In the 5-day postnatal aorta, extensive filament bundles extend along the subendothelial matrix connecting the endothelial cells to the underlying elastic lamina. The connecting filaments form lateral associations with the abluminal surface of the endothelial cells in regions of membrane occupied by membrane associated dense plaques. On the intracellular face of each plaque, the termini of stress fibers penetrate and anchor to the cell membrane in alignment with the extracellular connecting filaments. Both the stress fibers and the connecting filaments are oriented parallel to the longitudinal axis of the vessel. High magnification electron micrographs of individual endothelial cell connecting filaments reveal features similar to those of elastin-associated microfibrils. Each connecting filament consists of a 9-10 nm linear core with an electron lucent center and peripheral spike-like projections. From the filaments, small thread-like extensions span laterally, linking the filaments into a loose bundle and anchoring them to the endothelial cell membrane and the surface of the elastic lamina. The filaments also appear heavily coated with electron-dense material; often with some degree of periodicity along the filament length. During development, the number of endothelial cell connecting filaments decreases as the elastic lamina expands and the subendothelial matrix is reduced. In the aortic intima of mature mice, the elastic lamina is closely apposed to the abluminal surface of the endothelial cell and no connecting filaments are seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513478 TI - Dentin sialoprotein: biosynthesis and developmental appearance in rat tooth germs in comparison with amelogenins, osteocalcin and collagen type-I. AB - A non-collagenous protein, extracted from rat incisor dentin, is a dentin sialoprotein (DSP). We examined immunohistochemically the developmental appearance and tissue distribution of DSP in 1 to 3-day-old rat molar and incisor tooth germs. The earliest staining for DSP was observed in newly differentiated odontoblasts. In more advanced stages, immunostaining for DSP gradually increased in pre-dentin, odontoblasts and dentin, and appeared in many cells of the dental papilla. In early stages of development before the breakdown of the dental basement membrane, pre-ameloblasts were also positive for DSP. This staining disappeared from the ameloblast cell body soon after deposition of the first layer of mineralized dentin. Radiolabelling of tooth matrix proteins with 14C serine in vitro followed by immunoprecipitation and fluorography confirmed that DSP was synthesized by tooth-forming cells. The immunolocalization for DSP was different from that of either collagen type-I, osteocalcin or the amelogenins. Whereas collagen type-I and osteocalcin were restricted to the mesenchymal dental tissues, the amelogenins were detectable in both epithelial and mesenchymal dental cells and tissues at the epithelio-mesenchymal interface at early stages of development, prior to the onset of dentin mineralization. We conclude that DSP is expressed in and secreted by odontoblasts and some dental papilla cells from early stages of dentinogenesis onwards, i.e. later than type-I collagen, but before deposition of the first layer of mineralized dentin. In pre-mineralizing stages, some of the matrix proteins may be endocytosed from the pre-dentin by both cell types involved in the epithelio-mesenchymal interaction. PMID- 8513479 TI - Neurofilaments in rat and cat spinal cord; a comparative immunocytochemical study of phosphorylated and non-phosphorylated subunits. AB - Neurofilament immunoreactivity was examined in spinal cords of rats and cats with antibodies to all three subunits (68 kD, 155 kD and 200 kD) and to different phosphorylation states of 200 kD. NFHP-, an antibody against non-phosphorylated 200 kD, labelled all rat neuronal perikarya but failed to label cat neurofilaments. In both species, the perikarya and processes of motoneurones were immunoreactive for all three subunits but most dorsal horn neuronal perikarya were not immunoreactive for 68 kD and 155 kD. Motoneuronal perikarya and proximal processes showed filamentous labelling for 68 kD but not for 155 kD in the rat, while in neither species did these show labelling with RT97, an antibody against a highly phosphorylated form of 200 kD; immunoreactivity for 200 kD was present in both filamentous (probably partially phosphorylated) and non-filamentous (non phosphorylated) forms, but in dorsal horn neurones only the latter was present. Interpretations consistent with this data are: in rat and possibly also cat, motoneuronal neurofilaments consist of a 68 kD backbone with partially phosphorylated 200 kD sidearms, with both 155 kD and 200 kD (nonphosphorylated) subunits in a non-filamentous form; this neurofilament becomes more highly phosphorylated along the proximal processes. The dorsal horn neurones probably contain 200 kD in a non-filamentous form but may lack the other subunits. PMID- 8513481 TI - Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. AB - The mechanisms of intercommunication between the immune and nervous systems are not fully understood. In the case of the intestine, the enteric nervous system is involved in the regulation of immune responses. It was therefore decided to employ immuno-histochemical techniques to investigate the structural organization of the enteric nervous system in Peyer's patches of the porcine small intestine. Using antibodies against various nervous system-specific markers (protein gene product 9.5, neuron-specific enolase, neurofilament 200, S-100 protein and the glial fibrillary acidic protein), an intimate and specific structural association could be demonstrated between enteric nerves and the compartments of Peyer's patches: follicles, interfollicular regions and domes. Peyer's patches have a close topographical relationship to the two submucosal plexuses. Enteric nerves are located around the follicle in the interfollicular area--the so-called "traffic area"--and in the dome area, which plays an important role in the uptake and presentation of antigens. PMID- 8513480 TI - Immunocytochemical and electron-microscopic characterization of macrophage/microglia cells and expression of class II major histocompatibility complex in the pineal gland of the rat. AB - Interstitial cells in the pineal gland of the rat were characterized immunocytochemically using the monoclonal antibodies MRC OX-42 and ED1 for macrophages/microglia, and MRC OX-6, which recognizes major histocompatibility complex (MHC) class II antigen. A polyclonal antibody against GFAP was used to identify astrocytes. Cells immunopositive for OX-42 and/or ED1 were distributed throughout the gland; they extended processes primarily along the perivascular spaces and occasionally within the parenchyma of the gland. Ultrastructurally, these OX-42-positive cells were characterized by a nucleus with sparse heterochromatin and cytoplasmic vacuoles/lysosomes. Cells expressing MHC class II antigen had a distribution and morphology similar to OX-42-immunopositive cells, suggesting that pineal macrophages/microglia play a role as antigen-presenting cells. GFAP-positive astrocytes were concentrated at the proximal end of the pineal where the pineal stalk enters the gland. The occurrence of antigen presenting cells in this circumventricular neuroendocrine gland has important functional implications as these cells may be mediators of neuroimmunomodulatory mechanisms, and involved in certain disease states such as autoimmune pinealitis. PMID- 8513482 TI - Distribution of NCAM-180 and polysialic acid in the developing tectum mesencephali of the frog Discoglossus pictus and the salamander Pleurodeles waltl. AB - The 180 kDa component of the neural cell adhesion molecule (NCAM-180), total NCAM (NCAM-total) and the polysialic acid modification of NCAM (PSA) show similar temporal and spatial regulation in the developing tecta of Pleurodeles waltl (salamander) and Discoglossus pictus (frog). Whereas NCAM-total is found throughout the tectal tissue on neurons and glia, NCAM-180 is only found on non proliferating neurons and in fiber layers. PSA is expressed by a subset of NCAM 180-positive cells. Western blots show that there is little polysialylated NCAM 140 in the developing amphibian tectum. Regions unstained for PSA and NCAM-180 correspond precisely to the growth zones of the tectum. NCAM-180 and PSA are not present in tecta of early larvae. Staining intensity is strongest at midlarval stages for both antigens. At metamorphosis, PSA is strongly downregulated, whereas NCAM-180 is downregulated in juvenile animals. Both antigens are still present in fiber layers of adult animals. In dissociated tissue culture of the frog tectum, NCAM-180 is not present on astrocytes, but on neuronal cells. Expression is enhanced at cell contact sites, suggesting that NCAM-180 is involved in cell contact stabilization. This study shows that general features of temporal and spatial regulation of NCAM isoforms and PSA are highly conserved in frog and salamander tecta, despite large differences in the rate of cell migration and the degree of lamination in these homologous brain regions. PMID- 8513484 TI - Co-existence of gonadotrophins (FSH, LH) and thyrotrophin (TSH) in single anterior pituitary cells of the musk shrew, Suncus murinus. AB - According to recent immunocytochemical studies of anterior pituitary cells, it is obvious that the "one cell-one hormone" theory must be modified. Many pituitary morphologists have demonstrated that there are some cells that contain two hormones. In this study, we demonstrate by means of immuno-electronmicroscopy the co-existence of gonadotrophins (FSH and LH) and thyrotrophin (TSH) in the same anterior pituitary cells of the musk shrew. These cells were remarkably altered in their ultrastructural features by either gonadectomy or thyroidectomy. Double labeling for gonadotrophins and thyrotrophin was present not only in the same cells but also in the same secretory granules. Our ability to demonstrate co existence of gonadotrophins and thyrotrophin in the same cell may be due to our selection of fixative and embedding media for electron-microscopic immunocytochemistry. Our conclusion that gonadotrophins and thyrotrophin are produced in a single cell type of the anterior pituitary gland in the musk shrew, i.e., thyrogonadotrophs, suggests the need to consider a modification of the classic scheme for classification of anterior pituitary cells. PMID- 8513483 TI - Postnatal development of the rat portal vein: correlation with occurrence of peptidergic innervation. AB - The portal vein of the rat is immature at birth, and is composed of an endothelium surrounded by undifferentiated cells of mesenchymal origin. Three days after birth, these cells have begun to differentiate and aggregate around the lumen to form two separate layers of perpendicularly oriented myoblasts, while a rich calcitonin gene-related peptide (CGRP) innervation is present around the vessel. In the internal circular muscle layer of the media myofibrils first develop on the endothelial side of the myoblasts, and then progressively reach the other side. In the longitudinal muscular layer of the media, which is separated from the circular layer by a connective lamina as early as 3 days after birth, myofibrils develop randomly in the cells. At the time of the enlargement of the longitudinal layer, long close contacts and intermediate junctions between external myoblasts and adventitial fibroblast-like cells were noted, suggesting that recruitment of this cell type is necessary for the maturation of the vessel wall. At about 28 days, the vein has reached its final structure and the smooth muscle cells are fully differentiated. The dense CGRP perivascular innervation already present at birth persists for the first 14 days of postnatal life when most of the cells have not yet acquired their complete contractile differentiation and are still capable of division. This innervation decreases transiently between 15-17 days, when the vessel acquires its spontaneous contractile activity, then rises to a peak between 20 and 25 days, and falls again. CGRP innervation, which is very scarce at 28 days, slowly increases during the peripubescent stage, by which time the adult structure of the vessel is established. Similar fluctuations in the density of peptidergic innervation were observed for substance P and neuropeptide Y, although these peptides were not yet present at birth and occurred only after 5 days. Vasoactive intestinal polypeptide- and bombesin-immunoreactive fibres were not found at any stage investigated. In addition to a description of the different cell-to-cell contacts which could play a role in the maturation of the vessel wall, we discuss the possible implication of the different peptides in the differentiation, maturation or maintenance of the vessel wall. PMID- 8513485 TI - Microliths in normal salivary glands of cat investigated by light and electron microscopy. AB - This investigation concerns the natural history of microlith in the salivary glands of cat. Microliths were detected in more sublingual than submandibular glands and were almost absent in the parotid. They were found intraparenchymally, intraluminally and interstitially, and ultrastructurally in phagosomes of acinar, ductal and myoepithelial cells, intermixed with the cytoplasm of degenerate acinar cells, and in intraparenchymal macrophages and a multinuclear giant cell. They appear to form in healthy acinar cells during autophagocytosis, and possibly to be discharged luminally, laterally or basally, and to form in the debris of degenerate cells intraparenchymally and intraluminally. They appear to be removed by expulsion in the saliva, scavenging macrophages, and possible eventual degradation in the parenchymal phagosomes. The greater occurrence of microliths in the sublingual gland may relate to a low level of secretory activity, and the near absence of microliths in the parotid to a low level of calcium. The feline salivary glands were found to be an outstanding model for the investigation of microlithiasis. PMID- 8513486 TI - Thymic nurse cells in culture: morphological and antigenic characterization. AB - Epithelial monolayers were derived from thymic nurse cells (TNC), and were seeded onto collagen-coated dishes immediately after their isolation from young adult C3H-murine thymuses. Different media and supplements were tested in order to obtain cultures that were as pure as possible. Primary cultures were enriched in epithelial cells but always contained non-epithelial components among which fibroblasts predominated. Immunodetection of keratins, and repeated light- and electron-microscopic observations established the epithelial nature of the elongated cells derived from TNC; these elongated cells were cortical reticular cells, and were different from medullary globular cells that immediately adopted a mosaic pattern in vitro. At the beginning of the culture, the necrosis of cortical lymphocytes appeared to be toxic for epithelial cells; when epithelial cells survived, they showed a temporary lipid accumulation. After a 5-day culture, they still synthesized DNA but lost this capacity thereafter and dedifferentiated. The lympho-epithelial symbiosis appeared to be necessary to maintain some epithelial characteristics of the cultured cells, such as the clear vesicles and the expression of Ia antigens. In sub-cultures, the monolayers were almost purely epithelial in nature but growth was no longer observed. The cells remained reticular in shape, as they were in vivo, but their cytoplasm and their nucleus became larger and numerous cells were multinucleated. Confluence was not obtained with classical media even after mitogenic stimulation. The frequent observation of strongly keratinized areas suggested a process of terminal differentiation; this could not be avoided by using low serum concentration. PMID- 8513487 TI - Immunocytochemical studies of chicken somatotrophs and somatotroph granules before and after hatching. AB - Immunocytochemical methods were used to gain information about the embryonic development of chicken somatotrophs before and after hatching. To localize growth hormone, anterior pituitary sections were incubated with growth-hormone antibody, and then an indirect peroxidase method was used for light microscopy and an immunogold method for electron microscopy. The earliest evidence of embryonic somatotrophs was seen at 12 days. At this stage somatotrophs were sparse (0.2% of parenchymal cells) and their granules were pleomorphic with elongated ovoid and lozenge shapes predominating. Few of the immunogold-labeled somatotroph granules of the embryo were spherical until 15 days after fertilization. At 18 days, most of the granules were spherical (their shape in the adult chicken). During the six days between the 15-day-old embryo and the 1-day-old chick, the number of gold particles per granule section approximately doubled suggesting an increase in growth hormone content of the granules. This rise was the result of increases in the size of the granule sections and in the concentration of gold particles in the sections. During the embryonic period of 12-20 days, somatotrophs were not more than 3.6% of the anterior pituitary cell population. During the following two days, between the 20-day-old embryo and the 1-day-old chick, the percentage of somatotrophs in the pituitary parenchymal cell population rose rapidly from 3.6% to 20.7% and then increased slowly to 24.6% during the period of 1-5 days after hatching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513488 TI - Ultrastructural localization of carbohydrates in Reichert's membrane of the mouse. AB - In the present investigation, we examined the role of trophoblast and parietal endoderm cells in the synthesis of carbohydrate-containing components of Reichert's membrane. To eliminate the function of Reichert's membrane as a filter between maternal and embryonal tissues we carried out our examination under in vitro conditions. Parietal yolk sac from mouse embryos on day 9 post coitum (p.c.) were cultivated for 0 to 5 days. Because tannic acid enables a complex formation between carbohydrates and osmium we chose the fixation with this acid for the ultrastructural study. Electron microscopy showed that for assembly of Reichert's membrane, trophoblast cells produce and then release components that were detected as tannic acid-positive granules both in the Reichert's membrane and in the vacuoles of the trophoblast cells. To localize specific carbohydrates we used postembedding-gold-lectin histochemistry on LR-GoldR-embedded tissues. Strong binding sites for the lectins WGA (Triticum vulgare), RCA I (Ricinus communis) and Con A (Canavalia ensiformis) were observed in Reichert's membrane and trophoblast cells but not in the parietal endoderm cells. The LTA (Lotus tetragonolobus)-binding pattern was positive in the membrane and its adjacent cells but that of the LFA (Limax flavus) was negative in the parietal endoderm cells and very weak in Reichert's membrane and trophoblast cells. Our results demonstrate that trophoblast cells are involved in the construction of Reichert's membrane through the production and release of specific glycoconjugates. PMID- 8513489 TI - Irregular distribution of mammary-derived growth inhibitor in the bovine mammary epithelium. AB - Localization of a mammary-derived growth inhibitor (MDGI) in the bovine mammary gland was verified by light- and electron-microscopic methods. Expression of MDGI, which is known to inhibit the growth of mammary epithelial cell lines in vitro, was found to be highest in the late pregnant and in the lactating state. A combination of immunohistochemical and immunocytochemical methods with semi- and ultrathin resin sections revealed marked variations in MDGI staining. High MDGI levels were predominantly detectable in epithelial cells with large milk fat droplets. Distinct cell types that were almost free of label could be identified among bovine mammary epithelial cells that always exhibited high MDGI levels. Similar results were obtained when using a serum-free organ culture system in which MDGI was hormonally induced in cell types of comparable differentiation state. The specific occurrence of the growth inhibitor in developing alveoli and certain cell types points to the association between MDGI expression and functional differentiation in the normal mammary gland. PMID- 8513490 TI - Atrial natriuretic peptide binding in rat placenta, yolk sac, decidua, and maternal placental vessels. AB - Using in vitro autoradiography, binding sites of 125I-ANP (atrial natriuretic peptide) were localized in the rat placenta, visceral yolk sac, and decidua at 16, 18, and 20 days of gestation. There was diffuse binding over the labyrinthine region of the placenta and an intense binding over the decidual gland and visceral yolk sac. In the yolk sac, ANP localized over the cores of the villi where it may be involved with the regulation of transport across the membranes or the flow of blood through the vitelline vessels. Of particular interest was binding over the maternal blood vessels supplying the decidual region and placenta. Receptors were located on the endothelial cells and smooth muscle cells of the arteries and veins, indicating that ANP may be involved with regional regulation of blood flow to the placenta. PMID- 8513491 TI - Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? PMID- 8513492 TI - Mammalian G1 cyclins. PMID- 8513493 TI - Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. AB - Retroviral Gag protein is capable of directing the assembly of virion particles independent of other retroviral elements and plays an important role early in the infection of a cell. Using the GAL4 two hybrid system, we screened a cDNA expression library and identified two host proteins, cyclophillins (CyPs) A and B, which interact specifically with the human immunodeficiency virus type 1 (HIV 1) Gag polyprotein Pr55gag. Glutathione S-transferase-CyP fusion proteins bind tightly to Pr55gag in vitro, as well as to the HIV-1 capsid protein p24. Cyclosporin A efficiently disrupts the Gag-CyPA interaction and less efficiently disrupts the Gag-CyPB interaction. The Gag-CyP interaction may be important for the HIV-1 life cycle and may be relevant to the pathology caused by this immunosuppressive virus. PMID- 8513494 TI - Complete vesiculation of Golgi membranes and inhibition of protein transport by a novel sea sponge metabolite, ilimaquinone. AB - We have identified a novel natural metabolite, ilimaquinone (IQ), from sea sponges that causes Golgi membranes to break down completely in vivo into small vesicular structures (called vesiculated Golgi membranes [VGMs]). Under these conditions, transport of newly synthesized proteins from endoplasmic reticulum (ER) to the cis-Golgi-derived VGMs is unaffected; however, further transport along the secretory pathway is blocked. Upon removal of the drug, VGMs reassemble rapidly into a Golgi complex, and protein transport is restored. By employing a cell-free system that reconstitutes vesicular transport between successive Golgi cisternae, we provide evidence that the inhibition of protein transport by IQ is specifically due to an inhibition of transport vesicle formation. In addition, like brefeldin A (BFA), IQ treatment prevents the association of beta-COP and ADP ribosylation factor to the Golgi membranes; however, unlike BFA treatment, there is no retrograde transport of Golgi enzymes into ER. PMID- 8513495 TI - cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. AB - cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration. PMID- 8513496 TI - The signal sequence moves through a ribosomal tunnel into a noncytoplasmic aqueous environment at the ER membrane early in translocation. AB - The signal sequence is in an aqueous milieu at an early stage in the translocation of a nascent secretory protein across the endoplasmic reticulum membrane. This was determined using fluorescent probes incorporated into the signal sequence of fully assembled ribosome-nascent chain-membrane complexes: the fluorescence lifetimes revealed that the probes were in an aqueous environment rather than buried in the nonpolar core of the membrane. Since these membrane bound probes were not susceptible to collisional quenching by iodide ions, the space containing the signal sequence is sealed off from the cytoplasm by a tight ribosome-membrane junction. The nascent chain inside the ribosome is also not exposed to the cytoplasm and apparently passes through an aqueous tunnel in the ribosome. PMID- 8513497 TI - Constitutive activation of Src family kinases in mouse embryos that lack Csk. AB - Csk is a novel cytoplasmic protein-tyrosine kinase that has been shown to inactivate members of the Src family of protein-tyrosine kinases in vitro. To examine the function of Csk in vivo, Csk-deficient mouse embryos were generated by gene targeting in embryonic stem cells. These embryos were developmentally arrested at the 10 to 12 somite stage and exhibited growth retardation and necrosis in the neural tissues. The kinase activity of p60c-src, p59fyn, and p53/56lyn in these embryos was greatly enhanced as an apparent consequence of enhanced specific activity. The increase in kinase activity was associated with an increase in tyrosine phosphorylation of several proteins, especially those around 85 and 120 kd. Thus, these results suggest that Csk indeed acts as an indispensable negative regulator of Src family kinases in vivo. PMID- 8513498 TI - Genes that control neuromuscular specificity in Drosophila. AB - In each abdominal hemisegment of the Drosophila embryo, an array of 30 muscle fibers is innervated by about 34 motoneurons in a highly stereotyped and cell specific fashion. To begin to elucidate the molecular basis of neural specificity in this system, we conducted a genetic screen for mutations affecting neuromuscular connectivity. We focus on 5 genes required for specific aspects of pathway (beaten path, stranded, and short stop) and target (walkabout and clueless) recognition. The different classes of mutant phenotypes suggest that neural specificity is controlled by a hierarchy of molecular mechanisms: motoneurons are guided toward the correct region of mesoderm, in many cases navigating a series of choice points along the way; they then display an affinity for a particular domain of neighboring muscles; and finally, they recognize their specific muscle target from within this domain. PMID- 8513499 TI - Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. AB - We have employed a method based on the Cre-loxP recombination system of bacteriophage P1 to generate a mouse strain in which the JH segments and the intron enhancer in the IgH locus are deleted. By analysis of immunoglobulin isotype switch recombination in heterozygous mutant B cells activated by lipopolysaccharide plus interleukin-4, we show that, on the mutant chromosome, switch recombination at the mu gene switch region is strongly suppressed, whereas the switch region of the gamma 1 gene is efficiently rearranged. These data demonstrate an independent control of switch recombination at individual switch regions and suggest that, in the process of switch recombination, the alignment of the recombining strands occurs independently of and probably after the introduction of double-strand breaks into the switch regions involved. PMID- 8513500 TI - LexA and lambda Cl repressors as enzymes: specific cleavage in an intermolecular reaction. AB - During the SOS response, LexA repressor is inactivated by specific cleavage. Although cleavage requires RecA protein in vivo, RecA acts indirectly as a coprotease by stimulating an inherent self-cleavage activity of LexA. In lambda lysogens, cleavage of lambda Cl repressor in a similar but far slower reaction results in prophage induction. We describe an intermolecular cleavage reaction in which the C-terminal fragment of LexA acted as an enzyme to cleave other molecules of LexA. The C-terminal fragment of lambda repressor cleaved the LexA substrates about as efficiently as did the LexA enzyme, suggesting that the slow rate of Cl self-cleavage results from a weak interaction between its cleavage site and the active site. PMID- 8513501 TI - The yeast SIS1 protein, a DnaJ homolog, is required for the initiation of translation. AB - The S. cerevisiae SIS1 gene is essential and encodes a heat shock protein with similarity to the bacterial DnaJ protein. At the nonpermissive temperature, temperature-sensitive sis1 strains rapidly accumulate 80S ribosomes and have decreased amounts of polysomes. Certain alterations in 60S ribosomal subunits can suppress the temperature-sensitive phenotype of sis1 strains and prevent the accumulation of 80S ribosomes and the loss of polysomes normally seen under conditions of reduced SIS1 function. Analysis of sucrose gradients for SIS1 protein shows that a large fraction of SIS1 is associated with 40S ribosomal subunits and the smaller polysomes. These and other results indicate that SIS1 is required for the normal initiation of translation. Because DnaJ has been shown to mediate the dissociation of several protein complexes, the requirement of SIS1 in the initiation of translation might be for mediating the dissociation of a specific protein complex of the translation machinery. PMID- 8513502 TI - Phase variation of H. influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. AB - The expression of H. influenzae fimbriae is subject to reversible phase variation between three expression levels. This phenomenon is controlled at the transcriptional level of two divergently orientated genes, hifA and hifB, encoding the major fimbrial subunit and the fimbrial chaperone, respectively. The hifA and hifB promoter regions were found to be clustered through an almost complete divergent overlap with a variable DNA backbone of repetitive TA units. Variation in the number of units changes the normally strictly constrained spacing between the -35 and -10 sequences and controls the bidirectional transcription initiation, thus forming a novel mechanism directing multiple gene transcription. PMID- 8513503 TI - Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. AB - The transcription of genes encoding soluble proteins that reside in the endoplasmic reticulum (ER) is induced when unfolded proteins accumulate in the ER. Thus, an intracellular signal transduction pathway must exist that mediates communication between the ER lumen and the nucleus. We have identified a gene in S. cerevisiae, IRE1, that is required for this pathway: ire1- mutants cannot activate transcription of KAR2 and PDI1, which encode the ER resident proteins BiP and protein disulfide isomerase. Moreover, IRE1 is essential for cell viability under stress conditions that cause unfolded proteins to accumulate in the ER. IRE1 encodes a transmembrane serine/threonine kinase that we propose transmits the unfolded protein signal across the ER or inner nuclear membrane. IRE1 is also required for inositol prototrophy, suggesting that the induction of ER resident proteins is coupled to the biogenesis of new ER membrane. PMID- 8513504 TI - The transactivator proteins VP16 and GAL4 bind replication factor A. AB - Many transcription factors can activate the initiation of DNA replication. We have used affinity chromatography to show that the acidic activation domains of the transcription factors VP16, GAL4, and p53 each bind selectively to human and yeast replication factor A (RPA). The binding is direct and to the largest subunit of the trimeric RPA complex, RPA-1. Mutations in VP16 that reduce the ability of GAL4-VP16 to activate polyomavirus DNA replication also compromise the binding of VP16 to RPA. We suggest that transcription factors may interact with RPA either to stabilize single-stranded DNA at a replication origin or to recruit DNA polymerase alpha to the replication initiation complex. PMID- 8513505 TI - Disruption of U8 nucleolar snRNA inhibits 5.8S and 28S rRNA processing in the Xenopus oocyte. AB - The nucleoli of vertebrate cells contain several snRNPs, of which only one, U3, has been assigned a role in rRNA processing. We present the primary sequence of Xenopus U8, a fibrillarin-associated nucleolar snRNA, and examine its expression through oocyte development. Antisense deoxyoligonucleotides were microinjected into Xenopus oocytes to deplete the endogenous pool of U8 RNA. Analysis of the mature rRNAs and rRNA intermediates that accumulate in the U8-depleted oocytes indicate that the U8 snRNP is essential for correct maturation of the 5.8S and 28S rRNAs at both their 5' and 3' ends. U8 is therefore a nucleolar snRNA implicated in a nucleolytic rRNA processing step other than 18S maturation. Evidence for a long-lived 5.8S rRNA intermediate (12S) in Xenopus is also presented. PMID- 8513506 TI - Increased IgE level as a marker of host-versus-graft disease: inhibition of this HVGD with a monoclonal antibody to IL-4. AB - BALB/c mice injected at birth with (BALB/c x C57BL/6)F1 hybrid spleen cells developed host versus graft disease (HVGD) with immunological features, such as various autoantibodies, immune complex nephritis, hepatosplenomegaly, and malignant lymphomas. In addition we found that the increased IgE levels correlated strongly with the histological grades or stages of the liver disease. In the sera of mice with HVGD and liver alterations, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were detected. The subclass of ASMA was IgG1, whereas the subclasses of ANA were IgG1, IgG2a, and IgG2b. When the recipient BALB/c mice were injected at birth and at Day 3 in addition also with monoclonal anti-IL-4 antibody 11B11, the increase of IgE and IgG1 was markedly reduced and the liver disease was drastically prevented. These observations suggest that IL-4 plays an important role in the initiation of the immunoregulatory function or pathogenesis of the allogeneic effects and that the monoclonal anti-IL-4 antibody 11B11 prevents the immunodysfunctions and the autoimmune hepatopathy in mice with HVGD. The increased IgE level in the serum is a good marker of HVGD. PMID- 8513507 TI - Expression and regulation of the porcine CD44 molecule. AB - The expression and regulation of porcine CD44 were studied under various experimental conditions and in the context of lymphocyte differentiational and functional status. The CD44 molecule was subject to antigenic modulation by the anti-CD44 mAbs to different degrees depending on the type of cross-linking reagent and could be induced to shed from the cell surface. The reexpression of CD44 on papain-denuded lymphocytes was heterogeneous, as about half of the cells failed to resynthesize the molecule after prolonged culture, whereas the rest of the cells had a high turnover. Stimulation of lymphocytes by mitogens caused prolonged, dose-dependent elevation of the expression of CD44. Expression of CD44 on lymph node cells was found to be correlated with the expression of CD2 and sIgM. A CD2-CD4-sIgM-CD44-MHC Class IIhiCD45+ cell subset was identified, which was present in small numbers in lymph nodes but was enriched in gut-associated lymphoid tissues. In the thymus, CD44 expression seemed to be correlated with the differentiation status of thymocytes. In general, the expression of CD44 in the lymphoid tissues tested appeared to be related to their level of cell migration capacity. PMID- 8513508 TI - Differential regulation of group A streptococcal peptidoglycan-polysaccharide (PG APS)-stimulated macrophage production of IL-1 by rat strains susceptible and resistant to PG-APS-induced arthritis. AB - The magnitude of the response of rat macrophages to group A streptococcal cell wall peptidoglycan-polysaccharide (PG-APS) stimulation is strain-dependent. A comparison of IL-1 expression between macrophages from a PG-APS-resistant (BUF) and PG-APS-sensitive (LEW) rat strain revealed that while mRNA levels for IL-1 alpha and IL-1 beta were equivalent for the two strains, supernatants from BUF macrophages were less potent than LEW supernatants at stimulating thymocyte proliferation and contained less immunoreactive IL-1 alpha and IL-1 beta protein. BUF and LEW macrophages expressed nearly equivalent levels of IL-1 receptor antagonist (IL-1ra) mRNA and secreted IL-1ra protein in supernatants. The ratio of IL-1/IL-1ra produced by macrophages may influence susceptibility versus resistance to PG-APS and is strongly suggestive of a regulatory role for macrophages in the pathogenesis of PG-APS-induced arthritis. PMID- 8513509 TI - Monoclonal antibody to the type II Fc receptor for human IgG blocks potentiation of monocyte and neutrophil IgG-induced respiratory burst activation by aggregated C-reactive protein. AB - The acute phase protein, CRP, when heat-aggregated (Agg-CRP), binds to human monocytes and neutrophils and potentiates the respiratory burst stimulated by heat-aggregated IgG (Agg-IgG). Earlier data from our laboratory and others have indicated that CRP binds to phagocytic cells at membrane sites associated with IgG Fc receptors. The present study utilized monoclonal antibodies (MAb) to determine whether the Agg-CRP potentiation of oxidative metabolism could be linked to activation through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Preincubation of monocytes with MAb 32.2, which recognizes an Fc gamma RI epitope distinct from its IgG binding site, had only a minimal (20%) inhibitory effect on Agg-IgG-induced luminol chemiluminescence (CL) and exerted no significant effect on its enhancement by Agg-CRP. MAb 10.1, which blocks IgG binding to Fc gamma RI, reduced Agg-IgG-induced monocyte CL by 40%, but did not alter the Agg-CRP mediated enhancement. In contrast, exposure to MAb IV.3, which binds to Fc gamma RII on monocytes and neutrophils and blocks IgG binding to this receptor, resulted in a greater than 70%, inhibition of Agg-IgG-induced CL and also significantly suppressed the enhancement by Agg-CRP. MAb Leu-11b, which reacts with Fc gamma RIII on neutrophils, reduced Agg-IgG-induced CL by 70% but did not suppress the Agg-CRP potentiation. Preincubation of monocytes and neutrophils with anti-Leu-M1, anti-CR1, or anti-CR3 failed to block Agg-IgG-induced CL or its enhancement by Agg-CRP. Although the potentiating effect of Agg-CRP on Agg-IgG elicited CL was blocked by MAb IV.3, this antibody failed to reduce binding of Agg-CRP to either monocytes or neutrophils. These results indicate that, although Agg-CRP does not bind to phagocytic cells at the IgG-binding determinant of Fc gamma RII, it alters Agg-IgG-induced cell activation through this receptor. PMID- 8513510 TI - The regulation of resistance to Schistosoma mansoni by a soluble alpha/beta TCR analog, produced by a cloned T cell hybridoma. AB - Immunity to Schistosoma mansoni is regulated by an auto-anti-idiotypic network. The T cells in this network interact through soluble regulatory factors. These studies describe a soluble suppressor-inducer factor (TsiF) derived from TCR+ suppressor-inducer clone Q37. Q37 is the fusion product of CD4+ T cells derived from S. mansoni-infected mice and TCR-, BW1100 thymoma cells. [35S]Methionine biosynthetically labeled TsiF was immunoprecipitated with mAb H57-597 (anti-pan alpha/beta TCR) and adsorbed with protein G-agarose. The eluted 72-kDa TCR analog was reduced with dithiothreitol. Components of 32 and 44 kDa were found on SDS PAGE. These components were analogous to the alpha and beta chains of the TCR, binding antigen, or expressing V beta determinants, respectively. TsiF suppressed delayed-type hypersensitivity to S. mansoni antigens in a genetically and antigenically restricted manner. TsiF totally abrogated protective immune response against S. mansoni. These soluble TCR analogs may idiotypically regulate the resistance to S. mansoni. Q37 is an appropriate source of a suppressor TCR analog for the molecular analyses of this idiotypic regulation. PMID- 8513511 TI - Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone. AB - Glucocorticoids are extremely potent immunosuppressive agents, capable of directly affecting the function of lymphocytes. We studied the effect of in vivo dexamethasone (DEX) administration on anti-CD3-induced lymphocyte proliferation and lymphokine production in mice. To characterize the kinetics and dose responsiveness of lymphocytes to DEX, splenocytes from BALB/c mice that had received a single dose of DEX in vivo were cultured in vitro with suboptimal and optimal concentrations of anti-CD3 monoclonal antibody. Cell proliferation in response to suboptimal concentrations of anti-CD3 was decreased by DEX doses of > or = 30 mg/kg; much higher doses (> or = 200 mg/kg) were required to inhibit cell proliferation in response to optimal anti-CD3 stimulation. Inhibition of suboptimal anti-CD3-stimulated proliferation was evident within 4 hr after DEX administration, was maintained for at least 24 hr, and was no longer evident at 7 and 14 days. Lymphokine secretion induced by optimal doses of anti-CD3 in vitro was differentially affected by in vivo DEX treatment. IL-1 alpha, IL-4, IL-6, IL 10, and IFN-gamma levels were decreased by treatment with low doses of DEX (30 mg/kg), whereas higher doses were required to inhibit production of IL-2, IL-3, and TNF. GM-CSF (granulocyte-macrophage-colony stimulating factor) was least susceptible to DEX inhibition. Low-dose (30 mg/kg) DEX treatment significantly reduced anti-CD3-stimulated production of most lymphokines tested at 4 and 12 hr; by 24 hr the levels of most lymphokines had begun to return to control values. Hence, our data indicate that administration of a single dose of DEX (30 mg/kg for 4 hr) results in significant suppression of lymphokine production and cell proliferation that precedes any significant cell loss and can be used as a reversible model of immunosuppression. PMID- 8513512 TI - Maintenance of normal T lymphocyte function after transfection with SV40 large T. AB - Human T lymphocytes in culture undergo cellular senescence similar to that observed in fibroblasts. We recently demonstrated that senescence of T lymphocytes can be postponed by transfection with SV40 large T. In the current study, we examine the functional activity of SV40 large T transfected T lymphocytes. Transfected T cells of both young and elderly subjects appear to display normal T cell function: they cease doubling upon removal of IL-2; in the presence of autologous adherent mononuclear cells they respond to mitogen stimulation and produce IL-2 and IFN-gamma during proliferation; and they express both IL-2 and transferrin receptors similar to those observed in mitogen stimulated nontransfected T cells. In addition, more than 90% of the transfected cells express both the CD4 and "naive" T cell marker, CD45RA. In order to investigate whether the lack of long-lived CD8+ cells reflects phenotypic restriction, separated CD4+ and CD8+ subpopulations were transfected with SV40 large T. All transfections resulted in extended life spans of CD4+, but not CD8+, cells. Therefore, although SV40 large T transfected T lymphocytes maintain normal function, while demonstrating an extended life span, the effect may be restricted to CD4+ cells. PMID- 8513513 TI - MHC recognition in colonization of the thymus by bone marrow cells. AB - The role of major histocompatibility complex (MHC) class I and II molecules in the process of colonization of the thymic microenvironment by lymphohemopoietic cells was analyzed in an in vitro experimental model. When lymphoid-depleted fetal thymus (FT) explants were cocultured with a mixture of bone marrow (BM) cells, from donors syngeneic and allogeneic to the FT, the cells syngeneic to the FT showed a developmental preference. Treatment of these cocultures with antibodies to MHC class I (H-2D, H-2K) or class II (I-E, I-A) molecules of the syngeneic cells led to preferential development of the allogeneic donor type cells. Incubation of either the FT or the BM cell inoculum with the antibodies prior to coculture indicated that the effect was exerted on the BM cells rather than on the thymic stroma. PMID- 8513514 TI - An epidermal growth factor receptor promoter construct selectively expresses in the thymus and spleen of transgenic mice. AB - To determine the range of tissues in which the human epidermal growth factor (EGF) receptor promoter is active, we created 12 independently derived lines of mice expressing a transgene consisting of human EGF receptor promoter and enhancer sequences fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. Analysis for the presence of CAT activity in these transgenic mice revealed that the human EGF receptor promoter construct was consistently active in the thymus and spleen. Thymocytes separated from thymic stromal cells of EGF receptor CAT mice demonstrated no CAT activity suggesting that expression in the thymus is confined to the thymic stroma, which consists mainly of epithelial cells. Thus, it should be possible to use the EGF receptor promoter construct described in this study to direct expression of a variety of foreign genes to the nonlymphocytic cells of the thymus and spleen so that the effect of these genes on the maturation and proliferation of thymocytes may be addressed. PMID- 8513516 TI - [Pharmacy and the present time]. PMID- 8513515 TI - [Pharmacy in Belgium]. PMID- 8513517 TI - NSAIDs and balanced analgesia. PMID- 8513518 TI - Preoperative diclofenac sodium reduces post-laparoscopy pain. AB - Post-laparoscopy pain can increase recovery time and delay patient discharge. While previous studies have focused on the problems of nausea and vomiting, the purpose of this study was to assess the effect of diclofenac (a non-steroidal antiinflammatory drug) in the treatment of post-laparoscopy pain. Diclofenac (50 mg) or placebo was administered pr randomly and double-blind, prior to induction of anaesthesia, to 46 women. Pain intensity was assessed by the patient using a visual analogue scale 1, 12 and 24 hr after surgery. Postoperative analgesic requirements and side effects were also studied. Diclofenac resulted in better pain relief at 24 hr (1.0 vs 2.5, P < 0.05) and reduced the number of patients who needed additional postoperative analgesics (7 vs 15, P < 0.05). There was no difference in the incidence of side effects. These data suggest that diclofenac reduces post-laparoscopy pain and postoperative analgesic requirements. PMID- 8513519 TI - Comparison between patient-controlled analgesia and intramuscular meperidine after thoracotomy. AB - A prospective randomized controlled study was performed to assess the efficacy and safety of patient-controlled analgesia (PCA) in patients undergoing thoracotomy. This method was compared with a conventional pain management technique consisting of regularly scheduled im injections of analgesics. Forty adult patients were randomly assigned to receive intravenous PCA or im meperidine treatment over a 48-hr period after surgery. Care was taken to optimize analgesia in patients of both groups. The McGill Pain Questionnaire, visual analogue and verbal-numeric scales were administered at regular intervals to measure various components of the patients' pain experience, degree of pain relief, adverse side effects and overall treatment efficacy. Functional recovery after surgery was also examined. The results showed good and comparable analgesia with both pain control methods. However, a greater number of patients receiving im injections required dosage adjustments than in the PCA group. Patients' and nurses' evaluations of overall treatment efficacy also favoured PCA treatment. There were no major group differences in the side effect profile. Recovery pattern was also comparable in the two groups except for the length of hospitalisation. There were fewer long-stay patients in the PCA than in the im group. Meperidine intake was similar in both groups but considerable interpatient variation was seen. In conclusion, PCA is a safe, effective and individualized treatment method for controlling pain after thoracotomy. There appears to be some clinical advantages of PCA over im dosing regimens for analgesia after thoracotomy. PMID- 8513520 TI - A comparative study of patient-controlled epidural fentanyl and single dose epidural morphine for post-caesarean analgesia. AB - In a prospective, randomized, double-blinded study, 23 patients who had undergone Caesarean delivery under epidural anaesthesia were assessed to evaluate the effectiveness of patient-controlled epidural analgesia (PCEA) with fentanyl compared with a single dose of epidural morphine for postoperative analgesia. Group A (n = 11) received epidural fentanyl 100 micrograms intraoperatively then self-administered a maximum of two epidural fentanyl boluses 50 micrograms (10 micrograms.ml-1) with a lockout period of five minutes for a maximum of two doses per hour. Group B (n = 11) received a single bolus of epidural morphine 3 mg (0.5 mg.ml-1) intraoperatively and received the same instructions as Group A but had their PCA devices filled with 0.9% NaCl. Patients were assessed up to 24 hr for pain, satisfaction with pain relief, nausea and pruritus using visual analogue scales (VAS). The treatments for inadequate analgesia, nausea and pruritus as well as time to first independent ambulation were recorded. The ventilatory response to carbon dioxide challenge was measured at four and eight hours. Pain relief, satisfaction with pain relief, and the use of supplemental analgesics were similar in both groups. The mean 24 hr dose of epidural fentanyl used by group A patients was 680 micrograms. Pruritus was less common in Group A patients at the 8 and 24 hr observation periods (P < 0.0125). Both groups experienced the same degree of nausea and clinically unimportant respiratory depression. We conclude that PCEA with fentanyl provides analgesia equal to a single dose of epidural morphine and may be suitable for patients who have experienced considerable pruritus after epidural morphine administration. PMID- 8513521 TI - Comparison of fentanyl, sufentanil and alfentanil during awake craniotomy for epilepsy. AB - Neurolept anaesthesia is used during awake craniotomy for epilepsy surgery. This study compares analgesia, sedation and the side effects of the newer opioids sufentanil and alfentanil, with those of fentanyl in patients undergoing awake craniotomy. Thirty patients were randomized into three groups, each received droperidol, dimenhydrinate and the chosen opioid as a bolus followed by an infusion. The opioid doses used were fentanyl 0.75 microgram.kg-1 plus 0.01 microgram.kg-1 x min-1; sufentanil 0.075 microgram.kg-1 plus 0.0015 microgram.kg 1 x min-1, and alfentanil 7.5 micrograms.kg-1 plus 0.5 microgram.kg-1 x min-1. There were no differences in the requirements for droperidol, dimenhydrinate or in the incidence of complications among the three groups. The total doses of the opioids required were fentanyl 4.9 +/- 1.3 micrograms.kg-1, sufentanil 0.6 +/- 0.2 microgram.kg-1 and alfentanil 149 +/- 36 micrograms.kg-1. Two patients became uncooperative requiring general anesthesia. The conditions for surgery, electrocorticography and for stimulation testing were satisfactory in all other patients. We conclude that the newer opioids did not offer any benefit over fentanyl. PMID- 8513522 TI - Prolongation of epidural bupivacaine analgesia with glycerin. AB - Glycerin has been used as a drug carrier/depot, but never with local anaesthetics. This study was an attempt to use the slow drug release mechanism to prolong the anaesthetic effects of bupivacaine in epidural block. Twenty-seven adults with cancer pain were prospectively selected according to their primary lesions and problems, but their allocation to study groups was randomized. Group I (n = 13), received 5 ml bupivacaine, 0.125% in normal saline via a previous implanted epidural catheter. When the pain returned to its original intensity, the same amount of the same strength anaesthetic dissolved in 50% glycerin was given via the same catheter. Group II (n = 14) received the same solutions, but in the reverse order. Also five patients in each group received plain 50% glycerin prior to administration of the anaesthetic solutions to serve as controls. The pharmacological effects were assessed by the blinded observers. Analgesia produced with glycerin solution was prolonged compared with the saline solution (12.2 vs 7.2 and 11.6 vs 7.4 hr, P < 0.01). The order of giving the solution did not produce any differences. Plan 50% glycerin did not produce analgesic effects. Neither motor blockade nor other adverse effects or complications were observed in either group. It was concluded that 0.125% bupivacaine in 50% glycerin administered epidurally is not neurotoxic. The prolongation of analgesia observed is attributed to the slow release of bupivacaine from the glycerin base which functions as drug depot. In addition to relief of chronic pain, this novel approach may have other clinical applications such as the relief of labour or postoperative pain. PMID- 8513523 TI - Vital capacity rapid inhalation induction technique: comparison of sevoflurane and halothane. AB - Induction of anaesthesia using the vital capacity rapid inhalation induction (VCRII) technique with either sevoflurane or halothane was compared. The induction time, characteristics, and acceptability were assessed. Thirty-two volunteers were given one of the vapours: 17 received sevoflurane and 15 halothane. Subjects were unpremedicated and breathed approximately 2.6 x minimum alveolar concentration (MAC) equivalent of either agent. There were no differences in the patients' cardiovascular or respiratory variables. The mean time for induction of anaesthesia with halothane (153 +/- 46 sec, SD) was slower than with sevoflurane (81 +/- 22 sec, SD, P < 0.05), reflecting its higher blood:gas solubility. There were fewer induction complications such as coughing and movement in the sevoflurane than in the halothane group. Subjects in the sevoflurane group found the smell of anaesthetic more acceptable than those in the halothane group (65% vs 13%, respectively). Subjects in both groups had no objection to undergoing the procedure again. It is concluded that both halothane and sevoflurane are effective in VCRII of anaesthesia without premedication. However, the slower speed of induction with halothane frustrated the anaesthetist because of the longer induction time, and may increase the chance of pronounced excitatory phenomena occurring. PMID- 8513524 TI - Interactions of pre-operative erythromycin administration with general anaesthesia. AB - Previous reports have demonstrated a gastric emptying effect of erythromycin due to a motilin-like mechanism. We studied 50 patients, scheduled for daycase laparoscopy, randomly assigned to one of two groups: Group P patients received 30 min before induction of anaesthesia, in a double-blind manner an infusion of 250 ml dextrose 5% while patients in Group E (n = 25) received 500 mg of erythromycin diluted in 250 ml dextrose 5%. An orogastric tube was inserted to measure both gastric pH using a pHmeter and residual gastric volume (RGV) using the phenol red dilutional technique. Six patients were excluded for surgical reasons. More patients in Group P (6/22) than in Group E (0/22) had RGV > 25 ml and more patients in Group P (17/22) presented with a gastric pH < 2.5 than in Group E (5/22), P < 0.05. Since coma and respiratory depression have been reported recently after midazolam and alfentanil administration in patients having received erythromycin, recovery conditions were assessed and were found to be comparable between groups. In conclusion, the administration of iv erythromycin before outpatient laparoscopy decreased residual gastric volume and increased gastric pH without affecting recovery from general anaesthesia. PMID- 8513525 TI - Cardiovascular stability with rapid intravenous infusion of ondansetron. AB - The acute cardiovascular effects of rapid iv administration of the antiemetic ondansetron, a selective serotonin (5-HT3) receptor antagonist were determined in a randomized, blinded, placebo-controlled study. Measurements of heart rate, blood pressure, oxygen saturation and respiratory rate were made preoperatively over a five-minute period which followed a two-minute infusion of the medication. Intraoperative and postoperative data were not collected. None of the variables recorded changed significantly during the infusion or in the observation period which followed. Within the limitations of this study, we detected no cardiovascular change in the five minutes between the end of the drug infusion and the induction of anaesthesia. PMID- 8513527 TI - Intraoperative complications of laparoscopic cholecystectomy. AB - We report a series of intraoperative complications of laparoscopic cholecystectomy. Three cases are presented in which subcutaneous emphysema associated with pneumomediastinum, pneumoscrotum, and pneumothorax with pneumomediastinum and ocular emphysema, respectively, developed intraoperatively. These events resulted in no major morbidity to these patients. Use of N2O and monitoring of airway and intraabdominal pressures are discussed. PMID- 8513526 TI - Contractility of fatigued diaphragm is improved by dobutamine. AB - The effects of dobutamine (DOB) on diaphragmatic fatigue were examined in 20 anaesthetized, mechanically ventilated dogs. Animals were divided into two groups: the DOB group (n = 10) and the control group (n = 10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation applied to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. Diaphragmatic contractility was assessed with transdiaphragmatic pressure (Pdi). After diaphragmatic fatigue, Pdi decreased at low-frequency (20 Hz) stimulation (P < 0.05), whereas the decrease was minimal at high-frequency (100 Hz) stimulation. In the DOB group, after producing fatigue, the continuous administration of 10 micrograms.kg-1.min-1 dobutamine iv for 30 min produced an increased Pdi at both frequencies of stimulation (P < 0.05). The Pdi returned to pre-fatigue values after cessation of dobutamine administration. In the control group, the speed of recovery from fatigue was much slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) in the two groups did not change throughout the experiment at any frequency of stimulation. We conclude that dobutamine improves contractility in fatigued diaphragm. PMID- 8513528 TI - Pulmonary oedema after lithotripsy in a patient with hypertrophic subaortic stenosis. AB - Pulmonary oedema in a patient with hypertrophic subaortic stenosis undergoing extracorporeal shock wave lithotripsy is described. This event occurred upon emergence from the bath. It is suggested that pulmonary oedema followed emergence because of a reduction in central venous pressures and a decrease in preload which led to transient dynamic obstruction. Treatment with beta adrenergic blockade reduced outflow tract obstruction. Anaesthetists should be aware of the haemodynamic consequences of immersion and emersion with extracorporeal shock wave lithotripsy. PMID- 8513529 TI - Epidural catheter disconnections. PMID- 8513530 TI - General vs regional anaesthesia for minor surgery. PMID- 8513531 TI - Fibreoptic intubation. PMID- 8513532 TI - Tracheal intubation and cervical injury. PMID- 8513533 TI - Upper airway obstruction by Ascaris worm. PMID- 8513534 TI - Pre-admission clinic. PMID- 8513535 TI - Cost of anaesthesia. PMID- 8513536 TI - Surgeon's skill key to ovarian cancer management. PMID- 8513537 TI - A strategy for the syncope workup. PMID- 8513538 TI - Conservative vs surgical treatment of hyperparathyroidism: which to choose, and when? PMID- 8513539 TI - Treating SLE nephritis: some guidelines. PMID- 8513540 TI - Hemodialysis-induced hypotension: the search for a cause. PMID- 8513541 TI - Theophylline in the ambulatory treatment of chronic obstructive lung disease: resolving a controversy. AB - BACKGROUND: Recent reports of a high frequency of theophylline toxicity, which usually occurs at theophylline blood levels > 20 micrograms/mL, coupled with the recent addition of metered-dose, inhaled anticholinergics to the beta-2 agonist inhalers already available for treatment of chronic obstructive pulmonary disease, has led some authors to suggest that theophylline should no longer be used in the ambulatory management of this disease. OBJECTIVE: The author suggests an alternate approach to theophylline dosing as a means of resolving the current controversy. SUMMARY: Because of the log-linear relationship between bronchodilation and blood level, little bronchodilator efficacy is lost by using a target therapeutic theophylline blood level of 10 +/- 2 micrograms/mL. This target provides a greater range between therapeutic and toxic blood levels than the 17 +/- 2 micrograms/mL therapeutic target blood level that has also been recommended. CONCLUSIONS: Because theophylline has a different mode of action than the sympathomimetic or anticholinergic drugs, it continues to have a useful place in the ambulatory management of chronic obstructive pulmonary disease. PMID- 8513542 TI - Acquired immunodeficiency syndrome: case reporting at a university hospital. AB - BACKGROUND: Planning and allocating resources for care of patients with acquired immunodeficiency syndrome (AIDS) requires accurate assessment of disease incidence. OBJECTIVE: To assess the accuracy and completeness of AIDS case reporting at our institution, we reviewed all inpatient and outpatient records of patients with AIDS seen at University Hospitals of Cleveland, Ohio, between January 1983 and July 1990. METHODS: The patients were identified through review of hospital discharge summaries, ambulatory clinic listings, and laboratory identification of opportunistic infections. RESULTS: We found that 24 of 291 AIDS cases (8%) seen at this institution had not been reported to state health departments. Of the 24 patients with unreported AIDS, 16 had received an AIDS diagnosis at other institutions, 11 had never been hospitalized at this institution, and 2 had used pseudonyms. CONCLUSIONS: Review of AIDS case reporting can ascertain the magnitude of underreporting; the profile of patients who were unreported may be used to evaluate the accuracy of reporting elsewhere and to identify systematic problems in case reporting methods. PMID- 8513543 TI - The role of multiple risk factors in cardiovascular morbidity and mortality. AB - BACKGROUND: Cardiovascular disease remains the leading cause of death in the United States. OBJECTIVE: To identify important modifiable cardiovascular risk factors and appropriate interventions. DISCUSSION: The three most important modifiable risk factors are hypertension, cigarette smoking, and dyslipidemia. Systolic hypertension poses a greater risk than diastolic, but the prognostic significance of diastolic blood pressure may have been underestimated. When a smoker quits, the cardiovascular risk soon approaches that of the nonsmoker. Cardiovascular risk increases progressively with elevations of the serum total cholesterol level above 200 mg/dL. Recently identified risk factors include hyperinsulinemia and left ventricular hypertrophy. CONCLUSION: Each patient deserves an evaluation of cardiovascular risk followed by education about and therapy for those risk factors that can be changed. When more than one risk factor is present, as is often the case, the increase in risk may be synergistic rather than additive. PMID- 8513544 TI - The changing profile of anesthetic practice: an update for internists. AB - BACKGROUND: Internists are commonly consulted to "clear" patients for anesthesia and surgery. Newer anesthetic agents and techniques now extend limits and possibilities beyond what many internists were taught. OBJECTIVE: To update internists on recent changes in anesthetic management and how they affect the preoperative evaluation. SUMMARY: Recent advances in anesthetic management include new monitoring standards, balanced anesthetic technique, new agents, equipment changes, better understanding of human factors, and expanded pain management techniques. CONCLUSIONS: Postoperative care will likely assume increasing importance in determining anesthesia-related morbidity and mortality. For this reason, increased interaction and cooperation between surgeons, internists, and anesthesiologists are needed. PMID- 8513545 TI - Noninfectious respiratory disease in pregnancy. AB - BACKGROUND: Pregnancy increases the risk of many noninfectious respiratory conditions. OBJECTIVE: To review the clinical presentation and management of a variety of noninfectious respiratory conditions in pregnant women. SUMMARY: Asthma, aspiration pneumonia, venous air embolism, adult respiratory distress syndrome, pulmonary embolism, and deep venous thrombosis may have unique features in pregnant women. CONCLUSIONS: Evaluation and treatment of these diseases and conditions requires an understanding of the normal physiologic alterations that accompany pregnancy and an awareness of the risks of medication use during pregnancy and in the postpartum period. PMID- 8513546 TI - Noninvasive risk assessment after myocardial infarction. AB - BACKGROUND: Mortality from acute myocardial infarction is substantially less than it was two and even one decade ago. This improvement in both short-term and postdischarge outcome results both from early interventions to restore myocardial perfusion and mitigate expansion and remodeling, and from later assessment and management of functional status at the time of hospital discharge. OBJECTIVE: Recent studies suggest that invasive evaluation of the patient who has had a myocardial infarction (MI) should not be recommended on a routine basis. This review provides an approach to the noninvasive assessment of the patient. DISCUSSION: Stress testing to ascertain post-MI ischemia, ejection fraction determination to evaluate ventricular volumes and function, and ambulatory electrocardiographic monitoring, electrophysiologic study, and signal-averaged electrocardiography to assess presence and type of ventricular ectopy are discussed. CONCLUSION: The approach to the post-MI patient offered herein is felt to be medically sound and cost-effective. Refinement and alterations in this approach will be necessary as outcomes in specific patient groups, such as thrombolysis patients, women, and the elderly, become clearer. PMID- 8513547 TI - Transdermal nicotine patches: how effective are they? PMID- 8513548 TI - A medical approach to nicotine addiction treatment. AB - Smoking cessation is a complex process, not a simple event. The cues that cause a smoker to light up, the life-style, and the fallacies of each smoker are helpful information for the practicing physician. Behavioral modification aimed at eliminating cues that initiate smoking together with the systematic use of pharmacologic replacement therapy can help some patients quit. Transdermal nicotine replacement appears particularly promising, and additional pharmacologic agents to deal with nicotine withdrawal may be worth trying. Our advice to practitioners who would like to get involved in smoking cessation is to (1) set up your own smoking cessation clinic; (2) be systematic; (3) don't be discouraged; (4) follow your patients until they either quit smoking or quit coming to your office; and (5) keep abreast of new developments in smoking cessation strategies. PMID- 8513549 TI - Histochemical localization of a beta-galactoside-binding lectin and its binding sites in developing and adult rat cochlea. AB - The presence of an endogenous rat beta-galactoside-specific lectin (S-Lac) and its specific binding ligands was analyzed, using a rabbit anti-human brain lectin of 14 kDa antibody (anti-HBL-14) and a probe consisting of a biotinylated derivative of the human lectin (HBL-biot) in adult and in developing rat cochleas. At PD1, some epithelial cells of the outer spiral sulcus (OSS) were specifically recognized by the anti-HBL-14 antibody. Then, anti-HBL-14 immunoreactivity progressively appeared in all OSS epithelial cells, and, from PD9 on, it also appeared in inner spiral sulcus (ISS) epithelial cells. Finally, young adult rats exhibited a well defined anti-HBL-14 immunoreactivity in epithelial cells of the inner and outer spiral sulcus. Using the biotinylated probe, from PD3 on, tectorial membrane (TM) and the sensory cells apical surfaces were labelled. The glycoconjugate expression within the developing organ of Corti seems to be highly complex. Lectin was detected in developing and adult epithelial cells surrounding the organ of Corti. In contrast, other glycoconjugates related to B and H human blood group antigens, were transiently present on sensory cells of the organ of Corti. Present findings can be correlated with significant events in development of the cochlea, mainly with cell-cell recognition or cellular adhesion. PMID- 8513550 TI - Sexually dimorphic effects of prenatal cocaine on adult sexual behavior and brain catecholamines in rats. AB - Exposure to cocaine in utero (10 mg/kg twice a day on days 11-18 of gestation) differentially altered adult sexual behavior, brain catecholamine levels and perhaps open field activity in male and female rats. Female rats exposed to cocaine were significantly inhibited in their sexual behavior when compared to saline-exposed controls. In contrast, males exposed prenatally to cocaine exhibited normal or even facilitated sexual behavior. In particular, the significantly shorter post-ejaculatory intromission intervals displayed by cocaine-exposed males indicated that these animals might have enhanced sexual arousal or motivation. In tests for open field activity, males consistently showed higher levels of rearing behavior than females. Prenatal cocaine tended to reduce rearing in females, but this effect was not significant. Cocaine-exposed male rats had significantly higher norepinephrine and dopamine levels in the preoptic area than saline-exposed controls, whereas cocaine did not affect catecholamine content in male hypothalamus, striatum, cortex or cerebellum. Cocaine- and saline-exposed females had similar catecholamine levels in all brain regions. These results suggest that exposure of developing animals to modest doses of cocaine during mid to late gestation results in long-lasting, sexually dimorphic alterations of adult sexual behavior and brain catecholamines in rats. PMID- 8513551 TI - Gonadal steroids modulate the growth-associated protein GAP-43 (neuromodulin) mRNA in postnatal rat brain. AB - Gonadal steroid hormone action during early postnatal life determines the growth and connectivity of certain neuronal populations in the hypothalamus. The results of recent studies indicate that steroid hormones modulate the growth-associated protein GAP-43 mRNA in the adult rodent hypothalamus. Since GAP-43 is concentrated in axonal growth cones and has been implicated in axonal elongation and synaptogenesis, the present study investigated the effect of various gonadal hormonal conditions on GAP-43 mRNA levels in postnatal rat brain. On postnatal day 1, male rats were castrated or sham-operated and injected with sesame oil. Additional intact female rats were also injected with oil, while a group of female pups were injected with testosterone propionate. On postnatal day 6, brains were frozen and 16-microns cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complimentary to GAP-43 mRNA. Slide-mounted sections were stringently washed, apposed to X-ray film and then dipped in liquid emulsion. Evaluation of slide and film autoradiograms revealed an extensive presence of GAP-43 mRNA in the medial preoptic nucleus, bed nucleus of the stria terminalis and cerebral cortex, while the intensity of hybridization signal in other brain regions including the striatum was low. Quantitative assessment of GAP-43 mRNA in the medial preoptic area revealed that the level of GAP-43 mRNA was highest in the sham-operated male, attenuated after male castration, low in the intact female and markedly augmented in the testosterone-treated female. The pattern of change in the bed nucleus of the stria terminalis and laminae II and III of the frontal cortex was similar to that observed in the preoptic area. The changes in hybridization signal were positively correlated with changes in serum testosterone levels as determined by RIA. The results of these studies indicate that GAP-43 mRNA levels in the medial preoptic area, bed nucleus of the stria terminalis and cerebral cortex are sexually dimorphic and modulated by changes in gonadal steroid hormone levels. The results further suggest that the differential regulation of GAP-43 mRNA by sex steroids in the male and female postnatal brain may influence the phenotype of forebrain neuronal circuitry and thereby determine the phenotype of adult neuronal function. PMID- 8513552 TI - Analysis of protein variations in adult and postnatal day 11 staggerer and lurcher mutant mice. AB - As an initial attempt at uncovering the molecular basis of cerebellar synaptogenic defects in the lurcher and staggerer mutant mice, the pattern of protein expression was compared between cerebellar and non-cerebellar tissues, between normal and mutant mice and between early postnatal and adult developmental stages. While cerebellar and mutation-specific alterations in the expression of proteins could be easily observed in adult tissues, no such alterations were observed in early postnatal lurcher mice and only one qualitatively unique protein species could reproducibly be identified in early postnatal staggerer mice. PMID- 8513553 TI - Age-dependent survival-promoting activity of vitamin K on cultured CNS neurons. AB - Neurons from the central nervous system (CNS) of rat embryos die within several days when seeded at a low density of 10(4) cells/cm2 and cultured in a serum-free defined medium. Using these culture systems, we searched for agents to promote the survival of these neurons. As a consequence, a fat-soluble vitamin, vitamin K1, was found to possess such kind of activity: more than 50% of the cortical neurons from 19-day-old rat embryos could survive for 4 days in the presence of vitamin K1, whereas almost all neurons died in its absence. The survival promoting effect of vitamin K1 was found on neurons from not only cortex, but also hippocampus, striatum, and septum. In addition to vitamin K1, vitamin K2 and K3 also showed the same effect on cortical neurons. The effect of vitamins K1 and K2 was observed at concentrations from 10(-8) to 10(-6) M, and that of vitamin K3 was slightly detected at 10(-6) M. Furthermore, we examined the effect on the neurons from 16- and 21-day-old embryos, too. The activity of vitamin K1 was weaker toward the neurons from 21-day-old embryos compared with that toward 19 day-old ones, and was not recognized toward 16-day-old ones. These results suggest the potential role of the K vitamins on the maintenance of the survival of CNS neurons during the later stages of embryogenesis in vivo. PMID- 8513554 TI - Regional expression of angiotensinogen mRNA in the brain of one-week-old, adult and old male rats. AB - The purpose of this study was to investigate possible regional differences in the distribution of angiotensinogen-mRNA in the postnatal versus the aging animal using in situ hybridization and computer-assisted microdensitometry. An essentially identical regional distribution pattern of angiotensinogen-mRNA in the brains of postnatal, adult and old rats was demonstrated. Substantial differences in angiotensinogen expression were observed in brain areas of postnatal versus adult and old animals. Also large differences were seen in the ratios of angiotensinogen-mRNA levels in different brain areas within one age. The medulla of young animals contained the largest amounts of angiotensinogen mRNA compared to hypothalamus and midbrain. In contrast, adult and old animals showed approximately the same expression levels in midbrain and medulla, whereas the largest amounts of angiotensinogen-mRNA were expressed in the hypothalamus. PMID- 8513555 TI - Differential expression and gonadal hormone regulation of histone H1(0) in the developing and adult rat brain. AB - The cellular distribution of histone H1(0) has been examined immunohistochemically in the rat brain. H1(0) accumulates in neurons and glial cells during postnatal development. In neurons, immunoreactivity increases progressively from about postnatal day 10, and reaches a distribution pattern similar to that of adult rats by postnatal day 20. Immunoreactivity in glial cells shows a prominent increase from postnatal day 20 to adult age. The accumulation of H1(0) during postnatal development appears to be correlated with terminal differentiation and maturation. Although immunoreactive neurons are widely distributed in all areas of the central nervous system, many neurons do not express immunoreactivity. For instance in the cerebellum, Purkinje neurons are negative. In females, the number of immunoreactive neurons in the arcuate area of the hypothalamus increases during postnatal development. In contrast, the percentage of immunoreactive neurons in males is low at all ages studied. The expression of H1(0) in the ventromedial part of the arcuate is reversibly and negatively regulated during the estrous cycle by the level of plasma estradiol. Ovariectomy increases the number of immunoreactive neurons while the restoration of the physiological levels of estradiol results in the opposite effect. Early postnatal androgenization of females suppresses the increment in the number of immunoreactive neurons in both the dorsolateral and the ventromedial parts of the arcuate during postnatal development, thus leading to permanently decreased levels of H1(0) immunoreactivity in postpuberal females. PMID- 8513556 TI - Expression of olfactory receptor and transduction genes during rat development. AB - The molecular components of olfactory reception and regulation are expressed in a tissue-specific manner. The functional attributes mediated by some of these proteins have been previously shown to display a well-defined developmental emergence during the last week of rat gestation. To gain a better understanding of the relations between chemosensory function and neuronal development, we studied the ontogeny of 7 olfactory-specific genes by quantitative PCR. Relative levels of expression during rat development were determined for each gene, starting at embryonic day 15 (E15) and ending at postnatal day 35 (P35). In addition, the level of expression of the different genes was quantified in juvenile rats. The onset of expression for olfactory receptors and the olfactory cation channel at embryonic day 19 (E19) coincides with the functional maturation of the sensory neurons. Olfactory G-protein and adenylyl cyclase are expressed earlier (approximately E16) while olfactory biotransformation enzymes appear later (E20-E21), just before birth. The sequence of developmental expression of olfactory receptor genes has possible implications to the establishment of neuronal connectivity in this sensory pathway. PMID- 8513557 TI - Effects of kindling on subsequent learning, memory, behavior, and seizure susceptibility. AB - To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures. PMID- 8513559 TI - Inhibition of t-[35S]butylbicyclophosphorothionate binding by convulsant agents in primary cultures of cerebellar neurons. AB - The characteristics of the picrotoxinin binding site present on the gamma aminobutyric acidA (GABAA) receptor were studied in neurons using primary cultures of cerebellar granule cells. The binding properties of these sites in intact cultured cells were compared with those measured in cultured cell membrane preparations. t-[35S]Butylbicyclophosphorothionate (TBPS) binding was performed in cultured rat cerebellar neurons grown for 13 days. Binding parameters (Kd and Bmax) were similar to those reported in the literature determined using brain membranes. However, equilibrium was reached faster when using intact cultured neurons. Convulsant compounds like picrotoxinin (PTX) and pentylenetetrazol (PTZ) competitively inhibited the binding of TBPS in this in vitro system. Convulsant organochlorine pesticides (gamma-hexachlorocyclohexane gamma-HCH or lindane and the cyclodienes aldrin, endrin, dieldrin and alpha-endosulfan) competitively inhibited [35S]TBPS binding in cerebellar neuronal cultures. Inhibitory affinity constant (Ki) values were in the nanomolar range, alpha-endosulfan and endrin being the most potent inhibitors corresponding to their high toxicity in mammals. Stereospecificity was also shown for HCH isomers, the non-convulsant isomers (alpha- and delta-HCH) being 15-30 times less potent in inhibiting [35S]TBPS binding than the convulsant gamma-HCH, while the beta-isomer was inactive. PMID- 8513558 TI - Short-interval amygdala kindling in neonatal rats. AB - The kindling paradigm provides a powerful tool for studying the generation, propagation and generalization of seizures. Such reproducible quantitative paradigms are a prerequisite for the experimental study of epilepsy in the developing brain. Kindling has been extensively utilized as a model of limbic seizures in the adult rat; amygdala short-interval kindling has been studied in > or = 15-day-old rats. We applied the short-interval kindling method, i.e., stimulation at every 15 min, to 7-12-day-old rats. Stage-5 behavioral seizures were achieved even in 7-day-old rats; however, the progression of behavioral kindling differed somewhat from that of older rats. Correlation of electrographic discharges and behavioral phenomena was inversely related to age. Reliable progressive amygdala discharges were difficult to assess in most < or = 10-day old rats. Spontaneous seizures occurred relatively frequently in younger age groups. The amygdala short-interval kindling paradigm is reproducibly and reliably applicable to rats during the 2nd postnatal week. The presence of progressive focal to bilateral-generalized seizures suggests a significant functional maturity of the amygdala-limbic circuitry at this age. PMID- 8513560 TI - Profound, reversible energy loss in the hypoxic immature rat brain. AB - The goal of this study was to compare the effects of oxygen deprivation on cellular energy state and pH in the developing and adult rat brain. Relative quantities of phosphocreatine (PC), inorganic phosphorus (P(i)), and nucleoside triphosphates (NTP), and intracellular pH, were determined using in vivo 31P NMR spectroscopy at different postnatal ages (postnatal day (P) 2-6, P9-13, P16-20, P23-27) in the hypoxic rat brain (7 min, 4% O2). While a significant increase in P(i) was seen at all ages during hypoxia, a severe but reversible reduction in concentrations of PC (80-100% decrease) and NTP (40-50% decrease) was observed only at P9-13. This dramatic response was not seen in older (> P16) or younger (< P6) animals. These latter groups responded with moderate decreases in brain PC (50-60% decrease) and NTP (20-40% decrease). In addition, the youngest animals showed much less intracellular brain acidosis than the other age groups. The transient period of development during which the brain exhibits heightened susceptibility to hypoxic energy failure coincides with known changes in brain energy production pathways and susceptibility to hypoxia-induced excitability. PMID- 8513561 TI - Relationship between alcohol consumption and the activity of GTP-binding regulatory proteins in human erythrocyte membranes. AB - Activity of stimulatory GTP-binding regulatory protein (Gs) in human erythrocyte membranes was assessed by activation of adenylate cyclase in S49 murine lymphoma variant cells to elucidate a relationship to alcohol consumption. In apparently healthy subjects, alcohol consumption < 50 g ethanol per week did not alter the Gs activity, but it was significantly higher (14.3%, P < 0.05) in moderate drinkers (50-150 g/week) than non-drinkers. Then, the Gs activity declined with a further increase in alcohol consumption (150-550 g/week). Those subjects with drinking levels of > 50 g/week also showed significant increases in other alcohol related markers, Na+, K(+)-ATPase and gamma-glutamyltransferase. The Gs activity was significantly low in alcoholics (a 34.9% reduction). No such reduction was noted in patients with other diseases. The results indicate that the Gs activity in erythrocyte membranes is an alcohol-related marker in humans. The variation of Gs activity is distinctive from those of other alcohol-related markers. PMID- 8513562 TI - Acceleration of hemoglobin glycation with aging. PMID- 8513563 TI - Ethanediol stabilised quality control serum for measurement of zinc. PMID- 8513564 TI - Serum trehalase activity in patients with rheumatoid arthritis. PMID- 8513565 TI - Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM. AB - The levels of magnesium (Mg), zinc (Zn) and copper (Cu) in the plasma, erythrocytes (RBC) and polymorphonuclear (PMN) and lymphocyte (L), leukocytes (WBC) of 45 diabetic children were compared to those of 12 normal children and were related to the diabetic control via HbA1 and fasting blood sugar (FBS) assessments. Mineral levels were determined via Zeeman-effect atomic absorption spectrophotometry following separation of plasma, RBC, and WBC fractions (PMN vs. M). ANOVA (four-way, blood components, by two-way, diabetic vs. normal children) was significant for Mg only (F = 4.60, P < 0.004). Plasma Mg and M-WBC Mg were significantly lower in children with diabetes (780 +/- 16 vs. 860 +/- 29 mumol/l and 519 +/- 33 vs. 866 +/- 86 micrograms/10(10) cells, respectively). RBC Zn was significantly lower in diabetic youngsters by t-test (0.48 +/- 0.012 vs. 0.57 +/- 0.046 per mumol/g Hgb, t = 2.79, P < 0.004), but the ANOVA for Zn was not significant. Cu level differences were not significant. HbA1 was predicted only by PMN-WBC Mg (F = 8.78, P < 0.04) and FBS by none. In conclusion, the mineral status of these diabetic children was altered in regard to Mg, but was mainly independent of diabetic control. PMID- 8513566 TI - Serum hyaluronic acid in healthy infants and children and its value as a marker of progressive hepatobiliary disease starting in infancy. AB - We have established reference ranges for the concentrations of hyaluronic acid in serum from 397 infants and children and measured serum hyaluronic acid at presentation and 1 year follow-up in 37 infants who presented with hepatobiliary disease in the first 6 months of life. In health, hyaluronic acid concentrations fell progressively from median (10-90 percentile) values of 93 micrograms/l (49 153) at 1-3 months of age to 20 micrograms/l (9-40) at 2-3 years and 16 micrograms/l (6-32) at 4-18 years. In patients at presentation, the hyaluronic acid concentration was raised in 11 of 15 with biliary atresia, 6 of 11 with alpha-1 antitrypsin deficiency and 6 of 11 with cryptogenic hepatitis of infancy. One year later, the 9 patients who developed progressive liver disease showed 2-6 fold increases in hyaluronic acid concentration while no increase was observed in the 28 with undetectable or mild disease. Increases in serum hyaluronic acid concentration appeared to be a better indicator of progressive liver disease in infancy than standard laboratory tests. PMID- 8513567 TI - Changes of lipid peroxide levels in blood and liver tissue of patients with obstructive jaundice. AB - Plasma lipid peroxide levels, hereafter referred to as PLP levels, were measured in a group of 40 apparently healthy controls and 64 cholelithiasis patients, 40 with and 24 without jaundice. Hepatic lipid peroxide (HLP) levels were also measured in 26 patients, 15 with and 11 without jaundice. There was a significantly higher mean concentration of PLP in the jaundiced patients than in the control or jaundice-free cases. However, the difference in PLP levels between the jaundice-free and the control cases was insignificant. Meanwhile, patients with jaundice had significantly higher HLP levels than those without jaundice. In the jaundiced cases, the increased PLP and HLP levels were clearly related to the serum levels of bilirubin respectively. In addition, the HLP levels were positively correlated with the PLP levels; however, in the non-jaundiced cases, there was little evidence of these two relationships. Patients with or without jaundice had lower plasma vitamin E levels in comparison to the control cases. The correlation of plasma vitamin E and PLP levels was weak in all of the jaundiced. However, when we subdivided the jaundiced into two groups, the correlation was strong in those with plasma vitamin E levels < 8.5 micrograms/ml, while the correlation was weak in those with plasma vitamin E levels > 8.5 micrograms/ml. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in cholelithiasis patients and there exists a negative correlation between low vitamin E and lipid peroxide levels in plasma. PMID- 8513568 TI - Epidermal growth factor in human breast cancer, endometrial carcinoma and lung cancer. Its relationship to epidermal growth factor receptor, estradiol receptor and tumor TNM. AB - Epidermal growth factor (EGF) and its receptor (EGFR) were measured in 60 breast cancers (BC), 6 benign mammary tumors (BM), 8 samples of normal breast (NB), 6 endometrial carcinomas (EC) and 30 lung cancers (LC). EGF was measured in plasma, saliva and urine from 20 patients with BC, before and after tumor excision, and in 8 patients with metastatic disease. The median EGF in BM and BC was significantly higher (P < 0.05) than in NB. No significant correlation between EGF and EGFR was found in BC. Neither tumor excision nor the spreading of the disease significantly modified the EGF concentrations in biological fluids. In LC there was an inverse relationship between EGF and EGFR (rs = -0.36; P = 0.09), which disappeared in normal lung. It is concluded that EGF may play a role in malignant transformation; however, the weak correlation between EGF and EGFR lessens the importance of EGF in either autocrine or paracrine stimulation of tumor growth. PMID- 8513569 TI - Biocytin-specific 110-kDa biotinidase from human serum. AB - Biotinidase purification from human serum was performed under new protocol. With HPLC biotinidase assay instead of colorimetric method and using non-ionic surfactant, 110-kDa biotinidase was discovered and co-purified in addition to the previously identified 76-kDa biotinidase. This newly identified enzyme accounted for 5% of the total biotinidase activity. Protein core of 110 kDa was estimated as 72 kDa by use of N-glycanase and SDS-PAGE analysis, while that of the 76-kDa enzyme was estimated as 59 kDa. Total amino acid analysis indicated 30% higher absolute amounts of amino acids in 110-kDa enzyme. The following differences were observed from kinetic study: the 110-kDa enzyme showed a 10-fold lower Km value and a 9-fold higher kcat/Km value for biocytin than those of 76-kDa enzyme. Thus, 110-kDa enzyme is more likely to be the physiological biocytin hydrolase (biocytinase), since the biocytin concentration in human serum is extremely low. The pathogenesis of an inborn error of the metabolism such as a variant form of biotinidase deficiency, which presented an atypical clinical course, might be related to these isoenzymes in terms of their different roles in the body. PMID- 8513570 TI - Increased platelet activating factor in the tracheal aspirates from neonates with patent ductus arteriosus. AB - We investigated platelet-activating factor (PAF) in the tracheal aspirate from 3 intubated low birth weight infants with symptomatic patent ductus arteriosus (PDA). PAF increased with the onset of symptomatic PDA and decreased to the control range soon after the ductal closure. The concentration of PAF in 26 samples taken during symptomatic PDA (median 16 pg/micrograms lipid phosphorus, range 1.4-1,200 pg/micrograms lipid phosphorus) was significantly higher than that of 31 samples from the same three patients during the periods without symptomatic PDA (median 1.9 pg/micrograms lipid phosphorus, range 0-12 pg/micrograms lipid phosphorus; P < 0.001). All 3 infants later developed chronic lung disease. These results suggest that large shunting PDA provokes PAF release to the air way of the neonate and that PAF might play a role in chronic lung disease developing after symptomatic PDA. PMID- 8513571 TI - Detection of heterozygotes for fructose-1,6-diphosphatase deficiency by measuring fructose-1,6-diphosphatase activity in monocytes cultured with calcitriol. AB - The increase of fructose-1,6-diphosphatase activity during culture with calcitriol, which was reported in monocytes, was found not to occur in lymphocytes. Monocytes cultured with calcitriol were accordingly used as more reliable diagnosis of heterozygotes for fructose-1,6-diphosphatase deficiency, instead of mononuclear cells (lymphocyte-fraction-containing monocytes) cultured without calcitriol by a conventional method. Variation of fructose-1,6 diphosphatase values in leukocytes from nine healthy adults was smallest in monocytes cultured with calcitriol, among four different experimental conditions: monocytes cultured with or without calcitriol and mononuclear cells cultured with or without calcitriol. Both parents of two sisters with fructose-1,6 diphosphatase deficiency were successfully confirmed as carriers of fructose-1,6 diphosphatase deficiency by this method. However, confirmation by the conventional method using mononuclear cells cultured without calcitriol was possible only in the father, not in the mother. Thus, the new method using monocytes cultured with calcitriol seems more reliable for detecting heterozygotes for fructose-1,6-diphosphatase deficiency. PMID- 8513572 TI - Further applications of blood gas analysis to gastric acidity determination. AB - It has been shown that the transient increase in total body bicarbonate that accompanies any acceleration of gastric acid secretion (the 'alkaline tide') is derivable from the associated changes in base excess in arterial blood and is precisely equivalent to the amount of acid secreted when the latter is simultaneously recovered. For the alkaline tide to qualify as a 'tubeless' measure of acid secretion, its equivalence to the latter has to be demonstrated without simultaneous aspiration of gastric juice. We therefore studied the course of the alkaline tide following pentagastrin injection and its relationship to pentagastrin-stimulated acid secretion as measured by aspiration on a separate occasion. In 12 duodenal ulcer patients, the sequential changes in base excess in arterial blood in response to pentagastrin invariably described coherent curves. Peak values occurred most frequently 45 min after injection. In 12 similar patients, alkaline tide 45 min after pentagastrin, as per analysis of arterialized venous blood, correlated well (r = 0.86) with 'peak acid output' (PAO) as measured by aspiration at another time. In 14 patients post vagotomy and pyloroplasty for duodenal ulcer, the 45-min alkaline tide was determined as above and PAO was predicted from the previously established regression-line: The 3 patients with recurrent duodenal ulceration had the highest predicted values for PAO, clearly discriminating them from the others. Measurement of alkaline tide holds promise as a valuable substitute for conventional gastric analysis. For the sake of accuracy, readings should be based on individually constructed time curves of base excess, in preference to the raw data. Arterialized venous blood appears to be satisfactory substitute for arterial blood for studies of this type. PMID- 8513573 TI - A new highly sensitive radioimmunoassay for human calcitonin useful for physiological studies. AB - A highly sensitive and specific radioimmunoassay (RIA) for human calcitonin-like immunoreactivity (CT-LI) has been developed. The assay is performed directly without extraction and may be used for measurements in plasma or serum as well as buffer solutions. The detection limit of the assay is < 0.4 pmol/l, intra- and interassay variations 5 and 10%, respectively when calculated from a control sample within the range of normal concentrations. The recovery of calcitonin (CT) varied between 87 and 118% in the concentration range 10-130 pmol/l. Measurements of CT-LI in sera from 70 normal individuals, showed significantly lower concentrations in women as compared to men, 7.4 pmol/l +/- 2.1 pmol/l and 9.1 pmol/l +/- 2.2 pmol/l, respectively (mean +/- S.D.), P < 0.005. The chromatographic profile of immunoreactive CT in normal serum was investigated by gel chromatography and high pressure liquid chromatography (HPLC) and showed heterogeneity of circulating CT-LI, but with the majority eluting corresponding to the elution position of synthetic human CT. The study of physiological variations in CT levels has so far been hindered by the limitations in assay sensitivity. It is hoped that the significantly improved sensitivity of the presently described assay may contribute towards the elucidation of the physiological functions of CT. PMID- 8513574 TI - Expression of glutamic acid decarboxylase (GAD) in the alpha, beta and delta cells of normal and diabetic pancreas: implications for the pathogenesis of type I diabetes. AB - One of the paradoxes of insulin-dependent diabetes mellitus is that the destruction of the pancreatic islets' endocrine cells is restricted to the insulin-producing beta cells, whereas the main autoantibodies, islet cell antibodies (ICA), are directed against all endocrine islet cells. GAD has recently been proposed as the main target of the humoral and cellular autoimmune attack to the islets, and since in rat pancreas this enzyme was expressed only in the beta cells, this provided an explanation for the cell specificity of the destructive process. The finding of GAD-positive cells in the islets of two diabetic patients, one of whom had completely lost the beta cells, led us to study in detail the distribution of GAD in normal human islet cells using a panel of GAD antisera and the double indirect immunofluorescence technique on cryostat sections, monolayer cultures and cytosmears. The results showed that GAD is present not only in the cytoplasm of beta cells but also in 69% of the alpha and 27% of the delta cells. GAD was not present, however, on the surface of the islet cells. These results suggest that the cellular distribution of GAD can not by itself explain the selectivity of beta cell destruction in insulin-dependent diabetes mellitus. PMID- 8513575 TI - Pinealectomy ameliorates collagen II-induced arthritis in mice. AB - To extend our previous findings that exposure to constant darkness (stimulation of endogenous melatonin release) as well as treatment with exogenous melatonin magnifies the severity of collagen-induced arthritis in mice, we have examined the effects of melatonin cutback by removing the pineal gland. Two strains of mice, DBA/1 and NFR/N, were subjected to surgical pinealectomy. The melatonin levels in sera were reduced by approximately 70% by the pinealectomy compared with the corresponding sham-operated controls. After 3-4 weeks of rest the mice were immunized with rat type II collagen to induce autoimmune arthritis, and the animals were kept in constant darkness during the experiments. In comparison with the controls, all groups of pinealectomized mice showed reduced severity of the arthritis by means of (i) a slower onset of the disease, (ii) a less severe course of the disease (reduced clinical scores), and (iii) reduced serum levels of anti-collagen II antibodies. These effects were not significant in all experiments, but the trends were always the same. Thus, the present result strengthen the hypothesis that high physiological levels of melatonin (which can be induced by exposure to darkness) stimulate the immune system and cause exacerbation of autoimmune collagen II arthritis, while inhibition of melatonin release (pinealectomy or exposure to light) has a beneficial effect. PMID- 8513576 TI - Mucosal macrophage subsets of the gut in HIV: decrease in antigen-presenting cell phenotype. AB - The effect of HIV infection on intestinal lamina propria macrophage subsets was investigated in 41 patients at various stages of HIV infection (asymptomatic HIV infection, n = 17; AIDS, n = 24). Duodenal biopsies taken from HIV patients at endoscopy were snap frozen and cryostat sections cut for immunohistochemical staining. MoAbs CD68 (EBM11, pan-macrophage marker), RFD1 (antigen-presenting cells) and RFD7 (mature phagocytic macrophages) were used to identify cell subsets using indirect immunoperoxidase or alkaline phosphatase. Double immunofluorescence using MoAbs to HIV proteins (p24, p17 and gp120) and RFD1 were used to identify HIV-infected antigen-presenting cells. Double immunofluorescence was also used to identify macrophages that expressed both RFD1 and RFD7 ('suppressor' macrophages). Intensity of HLA-DR expression in lamina propria cells was investigated using a MoAb to HLA-DR directly conjugated to glucose oxidase. The results show that there was no difference in overall density of macrophages, but there was a significant decrease in dendritic cells (RFD1+) in all clinical stages of HIV. There was no difference in the density of RFD7+ macrophages, nor was there a difference intensity of HLA-DR expression in lamina propria cells. Only four HIV-infected cells were positively identified in the 41 patients. This result suggests that the antigen-presenting arm of mucosal immune defences may be seriously compromised in HIV infection, and represents a further insult to mucosal immunity already impaired as a result of loss of CD4+ T lymphocytes. This may contribute to development of opportunist infection in the gut. PMID- 8513577 TI - Elevated levels of antibodies against sulphatide are present in all chronic chagasic and dilated cardiomyopathy sera. AB - A natural anti-sulphatide antibody was found to be present in the serum of every normal individual studied. The reactivity of the antibody was assessed by its interaction with galactosylceramide-I3-sulphate. Antigen-antibody binding was strongly blocked by 1 mM heparin, dextran sulphate and chondroitin sulphate A, and by 5 mM chondroitin sulphate B. Antibodies avidly absorb to rabbit erythrocytes, but discretely to rat erythrocytes, suggesting that they are different from galactocerebroside antibodies. Elevated levels of sulphatide antibodies were present in all of 102 chronic Trypanosoma cruzi-infected patients studied, but not in other patients having cutaneous or visceral leishmaniasis, T. rangeli infection or several other protozoal, helminthic or mycotic infections. Interestingly, 100% of 40 dilated cardiomyopathy patients also have elevated levels of sulphatide antibodies. As T. cruzi is rich in galactocerebroside sulphate, it is proposed that in chagasic patients this glycolipid could act as an immunogen, inducing elevated titres of sulphatide antibodies, which could be important in the pathogenesis of cardiac or peripheral nerve symptoms. PMID- 8513578 TI - Adjuvant treatment increases the resistance to Mycobacterium avium infection of mycobacteria-susceptible BALB/c mice. AB - We have investigated the effect of inflammation on host resistance against infection by Mycobacterium avium, an atypical mycobacteria species that is responsible for life-threatening opportunistic infections in AIDS patients. Inflammation was induced in BALB/c mice by two intraperitoneal injections of mineral oil (Freund's incomplete adjuvant, FIA). The BALB/c strain was chosen because it is naturally susceptible to Myco. avium infection. One week after the second FIA injection, the BALB/c mice were infected intravenously with 2.6 x 10(6) Myco. avium bacilli; at this time, the mice showed systemic granulocytosis because of the FIA injections. The kinetics of the murine infection was determined during 3 months by quantification of Myco. avium loads in the major target organs (liver and spleen) of the mycobacteria. The FIA treatment resulted in a significant decrease in the growth of Myco. avium in the infected BALB/c mice. This enhancement in host resistance to Myco. avium infection lasted for 2-3 months. In contrast with BALB/c animals, C3H mice (naturally resistant to Myco. avium infection) did not show an increased anti-Myco. avium action in association with the FIA treatment. The antimycobacterial effect of the FIA injections in BALB/c mice was compared with that produced by the injection of mycobacterial antigens (heat-killed Myco. tuberculosis) added to the mineral oil (i.e. Freund's complete adjuvant, FCA). The FCA treatment resulted in strong and sustained enhancements in the microbicidal capacities of BALB/c, and also of C3H mice. Data obtained with mutant athymic BALB/c mice revealed that the anti-Myco. avium effect of the FCA treatment was T cell-dependent. Our results indicate that: (i) non-immune inflammatory stimulation (FIA) of Myco. avium-susceptible hosts is able to cause a significant, albeit transient, increase in the resistance to Myco. avium infection; (ii) this protective effect is enhanced if heat-killed mycobacteria are added to the phlogistic agent (FCA), i.e. if a T cell-dependent response is induced; and (iii) systemic increase in the number of circulating granulocytes may help host defence against Myco. avium infection. PMID- 8513579 TI - Early IL-2/sIL-2R surge following surgery leads to temporary immune refractoriness. AB - High serum level of immunoreactive but not biologically active IL-2 was detected 1 day after surgery in patients undergoing major operation (abdominal, open heart), in proportion to the tissue injury caused by surgical trauma. IL-2 values were highest in those patients who underwent open-heart surgery and received blood transfusions. In all patients they declined in the third and fourth post operative days. Elevated serum levels of soluble IL-2 receptors (sIL-2R) were already present 1 day after operation, and peaked in the third and fifth post operative days after mitogen triggering. Blood lymphocytes derived from operated patients secreted reduced amounts of both IL-2 and sIL-2R compared with control lymphocytes. The extent and duration of this reduction were also proportional to the tissue trauma and were affected by blood transfusions. Based on these data we suggest that early post-operative systemic immunological activation (appearance of IL-2 in the serum) is followed by elevation of sIL-2R, which then interferes with IL-2-dependent immunity. Blood lymphocytes are probably not involved in the post-operative immunological activation. The trigger for and the site of IL-2/sIL 2R synthesis are not yet clear. PMID- 8513580 TI - Ultrastructural studies bearing on the mechanism of UVB-impaired induction of contact hypersensitivity to DNCB in man. AB - In both murine and human experimental systems, acute, low dose exposure of skin to ultraviolet B light (UVB) impairs the induction of allergic contact dermatitis (ACD) by haptens such as dinitrochlorobenzene (DNCB) in a significant proportion of individuals. By light microscopy, epidermal Langerhans cells (LC) have been reported to be depleted by UVB exposure as well as by epicutaneous hapten application, implying that LC may be the locus of action of the effects of both UVB and DNCB. However, light microscopy can not readily distinguish cell density changes secondary to LC necrosis from changes resulting from down-modulation of expression of LC surface molecules. Using a highly sensitive immunogold electron microscopic approach, we have evaluated the differential effects of UVB and/or DNCB on human epidermal LC. The results reveal that DNCB alone caused significant up-regulation of cell surface HLA class II expression on a very small number of LC, the major fraction of LC expressing normal levels of HLA class II. Furthermore, DNCB alone caused a modest reduction in the density of LC at the treated sites without evidence of cell necrosis. Treatment with UVB alone or UVB exposure followed by DNCB resulted in a reduction in the density of LC, with widespread evidence of LC necrosis. However, the few remaining intact LC were all intensely HLA class II-positive after UVB exposure followed by DNCB, whereas treatment with UVB alone did not result in changes in LC HLA class II expression. The findings that after DNCB painting only a small proportion of the LC were strongly HLA class II-positive, but after UVB exposure followed by DNCB all intact LC displayed significant up-regulation of cell surface HLA class II expression, imply that UVB exposure inhibits the migration of epidermal LC. This is consistent with the view that DNCB fails to induce ACD when hapten is painted on UVB-exposed skin because insufficient LC are available to initiate T cell activation in the draining lymph node. PMID- 8513581 TI - Pigeon breeders' lung; IgG subclasses to pigeon intestinal mucin and IgA antigens. AB - Sera from all symptomatics with pigeon breeders' lung and many non-symptomatic pigeon breeders react specifically with the pigeon antigens and in particular pigeon intestinal secretions and isolated pigeon intestinal mucin and IgA. In sera from all 82 precipitin-positive pigeon breeders investigated, IgG1 reacted with both IgA and mucin, while IgG2 reacted predominantly with mucin only. Sera from all 32 symptomatic patients with pigeon breeders' lung demonstrated an IgG3 reaction with mucin, but only three sera showed reactivity against IgA and this was very weak. In contrast, only three out of 27 pigeon breeders with pulmonary pathology other than pigeon breeders' lung and only three out of 23 sera from healthy pigeon breeders showed detectable IgG3 reactivity with mucin. IgG4 from eight sera only reacted with mucin (n = 7) or IgA (n = 1) and showed no consistent pattern between subject groups. Precipitin-negative sera from 30 volunteers with no previous pigeon exposure showed no IgG subclass reactivity with either the pigeon intestinal secretions or the isolated mucin and IgA antigens. These results show specific IgG2 and IgG3 subclass reactivity to pigeon intestinal mucin antigen in precipitin-positive sera from pigeon breeders. Further IgG3 subclass reactivity specific to pigeon mucin is strongly associated with sera from patients with the active pigeon breeders' lung disease. PMID- 8513582 TI - Concomitant enhancement of the response to Mls-1a antigens and the induction of post-thymectomy autoimmune gastritis in BALB/c mice. AB - We examined the role of Mls antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymectomy. The prevalence of AIG in Mls-1b mice which underwent thymectomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mls-1a DBA/2 mice it was < 6%. Whereas AIG-negative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-ME)-sensitive antiparietal cell autoantibody, AIG-positive BALB/c mice made 2-ME-resistant anti-parietal cell autoantibody. In addition, the prevalence of AIG in 3d-Tx BALB/c mice which were rendered tolerant to MIs-1a antigens by injection of bone marrow cells from (BALB/c x DBA/2)F1 mice within 24 h after birth was decreased compared with the non-tolerant control mice; the prevalence being 80% in the controls and 30% in the tolerant animals. Thus, the activation of helper T cells, including T cells responding to Mls-1a antigens and including immunoglobulin class switch, appeared to be closely associated with the induction of AIG. Flowcytometric analysis confirmed that CD4- V beta 6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of V beta 11 T cells, which are known to increase in 3d-Tx mice, occurred in the CD8, but not in the CD4 T cell population. Injection of MoAb to L3T4, but not Lyt2, V beta 6- or V beta 8-TCR, into 3d-Tx BALB/c and syngeneic nude mice which had received spleen cells of 3d Tx BALB/c mice bearing AIG completely abrogated the development of AIG, despite there being remarkable decreases in T cells expressing relevant markers to the injected antibodies in all the mice. These findings suggest that the increase of V beta 6+ L3T4+ T cells in AIG mice was concomitant with the activation of AIG inducing V beta 6- L3T4+ T cells. PMID- 8513584 TI - Divalency of the monoclonal antibody 5-1-6 is required for induction of proteinuria in rats. AB - A single i.v. injection of 3 mg of the F(ab')2 fragment of MoAb 5-1-6 into rats induced immediate proteinuria (128.1 +/- 80.7 mg/24 h on day 1) which lasted 1-2 days. In contrast, rats administered 10 mg of the corresponding Fab fragment did not develop abnormal proteinuria even though an equivalent dose of the intact MoAb 5-1-6 far exceeded the nephritogenic dose. The total kidney binding of 125I Fab fragment was 209.5 +/- 34.3 micrograms/2 kidneys. This exceeded that obtained by injection of 3 mg MoAb 5-1-6 IgG1 (58.9 +/- 12.5 micrograms/2 kidneys at 1 h) and was similar to that obtained following injection of 3 mg F(ab')2 fragment (235.3 +/- 16.9 micrograms/2 kidneys). Immunofluorescence (IF) showed a linear pattern along the glomerular capillary wall at 1 h after the administration of MoAb 5-1-6 IgG1, F(ab')2 or Fab fragment. On day 5, fine to coarse granules were observed scattered in F(ab')2-injected rat glomeruli, whereas granules were densely localized in Fab-injected rat glomeruli. Complement-depleted rats injected with 3 mg of MoAb 5-1-6 IgG1 developed proteinuria with the same time course as non-depleted rats. This observation, together with the ability of F(ab')2 to induce proteinuria, indicates that proteinuria induced by MoAb 5-1-6 is complement-independent. This study suggests that MoAb 5-1-6-induced proteinuria is initiated by cross-linking of the epitopes by divalent MoAb 5-1-6 and is independent of complement activity. PMID- 8513583 TI - Characterization of anti-acetylcholine receptor (AChR) antibodies from mice differing in susceptibility for experimental autoimmune myasthenia gravis (EAMG). AB - In the murine model for EAMG we investigated the relation between disease susceptibility and fine specificity of anti-AChR antibodies obtained from high susceptible C57Bl/6 and low susceptible BALB/c mice after immunization with Torpedo acetylcholine receptor (tAChR). Anti-AChR MoAbs with fine specificity for the main immunogenic region (MIR), the alpha-bungarotoxin (alpha BT)/acetylcholine binding sites and other extra- and intracellular epitopes were isolated from both mouse strains. In total, nine out of 38 MoAbs obtained from C57Bl/6 mice were directed against extracellular epitopes on mouse AChR in contrast to only one out of 27 MoAbs from BALB/c mice. A difference in antibody repertoire may underlie the difference in pathogenic response observed between these mouse strains. These results indicate that strain-specific differences in disease susceptibility in murine EAMG may be related to differences in the available repertoire of potential pathogenic antibodies. PMID- 8513585 TI - Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat. AB - Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1(1)) or BN (RT1n) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F1 hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F1 combination, but was much less frequent in BN-into-F1 SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F1 combination. In MLR, hepatic T cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F1 hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting. PMID- 8513586 TI - The influence of genetic factors on the immune response as judged by pneumococcal vaccination of mono- and dizygotic Caucasian twins. AB - Eighty-four mono- and dizygotic Caucasian twins randomly chosen, except for age and sex distribution, were vaccinated with a 23-valent pneumococcal vaccine. Blood samples were drawn before and after vaccination and the concentration of IgG, IgG1 and IgG2 pneumococcal antibodies was measured using an ELISA technique which only detects type-specific capsular antibodies, since C-polysaccharide antibodies in serum were removed. A significantly closer correlation was found regarding mean IgG and IgG2 antibody concentrations after vaccination in mono- compared with dizygotic twins, and this correlation was seemingly type-specific. Since environmental factors in our study population should not contribute more to the immune response in one type of twins compared with the other, we conclude that genetic factors influence the IgG and IgG2 antibody response to pneumococcal vaccination, and that this influence seems to be type-dependent. PMID- 8513587 TI - A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro. AB - Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera. PMID- 8513588 TI - Pathogenesis of thyroid-associated ophthalmopathy: an autoimmune disorder of the eye muscle associated with Graves' hyperthyroidism and Hashimoto's thyroiditis. AB - Thyroid-associated ophthalmopathy, the progressive eye disorder which occurs frequently in patients with Graves' hyperthyroidism and, occasionally, in those with Hashimoto's thyroiditis, may be a two-stage disorder of the eye muscle. In the first stage, which may occur in the great majority of patients with Graves' hyperthyroidism and in an unknown, but probably small, proportion of those with Hashimoto's thyroiditis, antibodies and CD4+ (helper) T lymphocytes reactive with eye muscle and thyroid shared antigens, of which 64-kDa membrane proteins are good candidates, may initiate a mild eye muscle inflammation, manifested as eye muscle swelling on orbital imaging. The second stage, which occurs in about 25% of patients with Graves' hyperthyroidism and in 2% of those with Hashimoto's thyroiditis, may be due to reactivity of cytotoxic antibodies against eye muscle specific membrane antigens, one of which at approximately 35 kDa appears a likely candidate, and, possibly, cytotoxic T cells in the context of the appropriate class I MHC molecule. Orbital connective tissue inflammation, which plays an important role in the development of progressive orbital inflammation, is likely to be secondary to the eye muscle reaction. The recent cloning of a 64-kDa thyroid and eye muscle antigen which shares significant homology with the muscle protein tropomodulin and mapping of its antibody-reactive epitopes provide structural information about one candidate eye muscle autoantigen and promise for a more rational approach to the diagnosis and management of this common, progressive eye disorder. PMID- 8513589 TI - Tumor necrosis factor-alpha, interleukin 1, eicosanoid, and hydrogen peroxide release from macrophages exposed to glove starch particles. AB - The inflammatory mechanisms leading to glove starch powder peritonitis are still unclear. This study was designed to examine the secretory potential of macrophages exposed to starch powder particles. Rat peritoneal macrophages and human monocytes were incubated in vitro with starch particles obtained from three commonly used surgical gloves. It was found that macrophages and monocytes released large amounts of tumor necrosis factor-alpha, interleukin 1, prostaglandin E2, thromboxane B2, and hydrogen peroxide. Release of these inflammatory mediators was associated with progressive cell death of macrophages. These data indicate that postoperative peritonitis and subsequent granuloma formation initiated by glove powder particles may be mediated and maintained, at least in part, by macrophage-derived cytokines, eicosanoids, and reactive oxygen intermediates. PMID- 8513590 TI - T cell receptor V beta usage in rheumatoid nodules: marked oligoclonality among IL-2 expanded lymphocytes. AB - Rheumatoid arthritis is an autoimmune disease which is characterized by chronic polyarthritis and joint destruction as well as by extra-articular manifestations, typically including the appearance of rheumatoid nodules. Although the pathogenesis of the disease is unknown, substantial evidence suggests that it is T cell-mediated. In contrast to experimental models, the disease-mediating T cells in the human situation have never been isolated or identified. We expanded T lymphocytes from human rheumatoid nodules by IL-2 stimulation and observed a marked oligoclonality among these expanded lymphocytes. This tendency towards oligoclonality was not seen in IL-2-expanded lymphocytes from peripheral blood. We hypothesize that this oligoclonal expansion reflects a clonally restricted in situ preactivation of lymphocytes and that precisely these preactivated cells are involved in the pathogenesis of the rheumatic process. PMID- 8513591 TI - In vivo upregulation of CD45RA in neutrophils of acutely infected patients. AB - The CD45 family of high relative molecular mass (M(r)) cell surface antigens is expressed on all lymphohematopoietic cells. Different cell types express various M(r) isoforms in a precisely programmed fashion. The cytoplasmic domain of the CD45 family possesses protein tyrosine phosphatase activity and is involved in transmembrane signaling. Under normal conditions, the major CD45 isoform on neutrophils is CD45RO, the low M(r) isoform. We recently demonstrated a cytoplasmic granule-associated pool of CD45RA, the highest M(r) isoform, in mature neutrophils that is generally absent from the cell surface under nonstimulatory conditions. Calcium ionophore A23187 induced translocation of cytoplasmic CD45RA to the cell surface and increased the cell surface expression of CD45RO and CD45. The present study demonstrates that without in vitro stimulation, there is an increase in expression of CD45RA on the surface of neutrophils from patients with systemic, acute infections, while those of patients with localized infections are only slightly increased compared to normal controls. Although the exact functions of the various isoforms of CD45 are not known, this increased expression of CD45RA suggests a role for this high M(r) isoform during in vitro neutrophil activation. PMID- 8513592 TI - Immunologic alterations in patients with sensorineural hearing disorders. AB - The autoimmune etiology suspected for some forms of hearing loss, supported by the clinical efficacy of steroid therapy, is thought to involve immune complexes, autoantibodies directed to the inner ear and/or cellular effectors. We report a study performed in 57 individuals with sudden deafness (n = 17, group 1) or progressive sensorineural hearing impairment (n = 40, group 2). A severe depletion in CD3+ and CD4+ peripheral lymphocytes was observed in group 1 and a marked decrease of CD8+ cells levels was observed in both groups. Group 2 patients frequently had anti-nuclear and anti-thyroid antibodies, while anti cochlear antibodies were found in both groups (respective incidences, 75 and 71%). Anti-cartilage antibodies, found with a similar frequency in both groups, were not correlated with anti-cochlear antibodies. These data suggest that different immune disorders are involved in the development of sudden and progressive deafness, while both types of sensorineural hearing impairment involve immune abnormalities. PMID- 8513593 TI - Extensive deletion of immunoglobulin heavy chain constant region genes in the absence of recurrent infections: when is IgG subclass deficiency clinically relevant? AB - This report describes two children with undetectable serum levels of IgA1, IgG2, IgG4, and IgE due to a homozygous deletion encompassing the A1-E genes. The father is a heterozygous carrier of the same deletion and the mother a heterozygous compound carrying the deletion on one chromosome and duplication on the other. In both children, serum IgG, IgG1, and IgG3 were higher than in normal children and IgG antibody response to tetanus toxoid and polysaccharide antigens was normal with increased IgG1 and IgG3 response compared to controls. The latter can be interpreted as a compensatory mechanism for the subclass deficit and may explain the lack of significant infections in both children. The importance of distinguishing IgG subclass deficiency due to gene deletion from that due to immunoregulatory dysfunction is discussed. PMID- 8513595 TI - Elevated soluble CD8 antigen and soluble interleukin-2 receptors in the sera of patients with juvenile rheumatoid arthritis. AB - Activated T lymphocytes release various molecules including soluble CD8 (sCD8) antigen and soluble interleukin-2 receptor (sIL-2R). Elevated serum sCD8 antigen levels have been found in patients with viral infections, certain hematologic malignancies, and rheumatoid arthritis. On the other hand, elevated serum levels of sIL-2R have been found in various diseases including juvenile rheumatoid arthritis (JRA). We measured sCD8 antigen and sIL-2R levels using enzyme-linked immunosorbent assays in the sera of 49 afebrile patients with JRA (systemic 15, polyarticular 16, and pauciarticular 18) and 16 normal children. Disease activity was classified as mild, moderate, and severe. Sera from patients with severe JRA expressed statistically significant higher levels of both sCD8 and sIL-2R, whereas patients with mild disease had the lowest levels. There were no differences in the serum sCD8 and sIL-2R levels between the groups of patients with pauciarticular-, systemic-, and polyarticular-onset disease. Patients who were treated with prednisone had statistically nonsignificant higher serum levels of sCD8 and sIL-2R. A statistically significant positive correlation was found between sCD8 and sIL-2R levels, sCD8 levels and erythrocyte sedimentation rate (ESR), and sIL-2R levels and ESR. Our findings further suggest the presence of activated lymphocytes in patients with JRA and show that sCD8 antigen serum levels correlate with both serum levels of sIL-2R and ESR and thus may represent alternative indicators of disease activity. PMID- 8513594 TI - Lymphokine regulation of granuloma formation in murine schistosomiasis mansoni. AB - The pathology in schistosomiasis mansoni is primarily due to hepatic and intestinal granuloma formation around deposited eggs and subsequent fibrosis. The intensity of the granulomatous response is dependent on the lymphokines produced by T cells in response to soluble egg antigens (SEA). The present study examined the relationship of three inflammatory lymphokines, IL-2, IL-4, and IFN-gamma in granuloma formation during the acute stage of the murine infection. Repeated injections of anti-IL-2 or anti-IL-4 mAbs in vivo significantly diminished pulmonary granuloma formation in infected mice and demonstrated that both IL-2 and IL-4 were involved during the period of peak granuloma formation. Administration of anti-IL-2 mAb decreased IL-2, but not IL-4 production, while anti-IL-4 mAb treatment decreased both IL-2 and IL-4 production by splenic T cells. Administration of anti-IFN-gamma mAb to infected mice significantly increased pulmonary granuloma formation and increased the production of both IL-2 and IL-4 by splenic T cells. Repeated injections of graded doses of recombinant IFN-gamma given to mice between 6 and 8 weeks of infection decreased pulmonary granuloma formation as well as IL-2 and IL-4 production by splenic T cells. These data demonstrate that the regulation of lymphokines, IFN-gamma, IL-2, and IL-4, is important in influencing the intensity of granuloma formation. IL-2 and IL-4 appear to play a proinflammatory role in granuloma formation, while IFN-gamma may downregulate splenic IL-2 and IL-4 production and, more importantly, the corresponding inflammatory granuloma formation. PMID- 8513596 TI - Patterns of T-cell receptor variable beta gene expression by synovial fluid and peripheral blood T-cells in rheumatoid arthritis. AB - Conflicting data have been reported regarding the presence or absence of a predominant variable (V) region T-cell receptor (TCR) gene in the peripheral blood or synovial fluid of patients with rheumatoid arthritis (RA). In this study we have used the polymerase chain reaction (PCR) to compare the level of TCR V beta gene expression by peripheral blood mononuclear cells (PBMC) and by synovial fluid cells obtained from HLA DRB1 *0401 and *0404 RA patients. PCR was performed using cDNA synthesized from freshly obtained cells (not stimulated in vitro). The pattern of expression observed for most of the V beta genes studied showed either preferential expression by PBMC or similar levels of expression between PBMC and synovial fluid T-cells. However, among individual patients (N = 5), several V beta genes were identified that were expressed to a significantly greater degree by synovial fluid cells. V beta 14 expression was detected in PBMC of all patients and the level of transcripts encoding V beta 14 increased following stimulation with immobilized anti-CD3 and IL-2. In vitro manipulation of populations of T-cells was found to alter the level of expressed V beta gene products. A V beta gene common to all patients that was consistently deleted from PBMC or expressed to a greater degree by resident, unsorted synovial fluid cells compared to PBMC was not identified. PMID- 8513597 TI - Murine susceptibility to mercury. II. autoantibody profiles and renal immune deposits in hybrid, backcross, and H-2d congenic mice. AB - Inorganic mercury causes systemic autoimmunity and/or immune-complex deposits in strains of mice carrying certain H-2 haplotypes, for example H-2s and H-2d. This study aimed at describing the genetic mechanisms regulating these reactions. Inbred SJL, C57BL/6J (B6), C57BL/10J (B10), and DBA mice, F1(SJL x DBA), F1(SJL x B6), and F2(SJL x B6) hybrids, and mice derived from a backcross of SJL or B6 mice to F1(SJL x B6) hybrids were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl every third day for 6 weeks. SJL mice developed a high titer of serum antinucleolar antibodies (ANoA) of the IgG class targeting the nucleolar protein fibrillarin and a significantly increased titer of IgG and C3 colocalized as granular deposits in the renal mesangium and vessel walls. The B6 and DBA strains lacked ANoA and showed no increase in titers of immune deposits. Nine percent of mercury-treated F1(SJL x DBA) hybrids developed IgG ANoA which were of a low titer, and only occasional hybrids showed an increased titer of granular mesangial IgG deposits. Mercury treatment induced ANoA of low titer in 41% of F1(SJL x B6) hybrids, and 24% had increased granular mesangial immune deposits. Four of 61 mercury-treated BC-[SJL x F1(SJL x B6)] mice showed ANoA which were of a high titer and targeted the nucleolar protein fibrillarin. ANoA were not found in 55 mercury-treated F2(SJL x B6) hybrids or in 56 mercury treated mice derived from a backcross of B6 mice to F1(SJL x B6) hybrids. Increased mesangial immune deposits were regularly accompanied by vessel wall deposits in F1- and F2(SJL x B6) hybrids, but only 53% of BC(SJL x F1[SJL x B6]) mice with increased mesangial deposits had vessel wall deposits. Vessel wall immune deposits were only present in mice with increased mesangial deposits. A majority of mice which developed significantly increased titers of mesangial IC deposits showed no ANoA. In conclusion, the susceptibility in SJL mice to develop ANoA during mercury treatment, which has been shown to reside in the H-2A locus, was codominantly inherited in a cross with mice carrying the H-2b and H2d haplotypes. Non-H-2 genes dampened ANoA expression to a degree which varied between the strains. Since renal vessel and mesangial IC deposits developed in backcross mice lacking serum ANoA, these deposits must contain IC not related to fibrillarin-antifibrillarin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513598 TI - Urine glycosaminoglycans and heparan sulfate excretions in adult patients with glomerular diseases. AB - We measured the concentrations of urine glycosaminoglycans (GAG) by the modified dimethylmethylene blue method and the concentration of urine heparan sulfate (HS) by enzyme-linked immunosorbent assay (ELISA) in patients with various glomerular diseases. The GAG/creatinine(Crea) ratios in patients with IgA nephropathy (mean +/- SD, 0.31 +/- 0.056) and membranous nephropathy (0.41 +/- 0.115) were significantly greater than in healthy controls (0.18 +/- 0.045). Urine GAG/Crea ratios in minimal change nephrotic patients increased during remission (0.38 +/- 0.102) and decreased to normal values during the nephrotic stage (0.25 +/- 0.088). In contrast, urine HS/Crea ratios in patients with minimal change nephrotic syndrome decreased during remission (0.0069 +/- 0.0029) and increased markedly during the nephrotic period (0.047 +/- 0.0007 versus controls 0.0158 +/- 0.0046). Serial measurement in three minimal change nephrotic patients showed the similar change for the HS/Crea ratio and urine albumin excretion in the course of steroid therapy. The loss of HS from the glomerular basement membrane (GBM) may therefore be related to the pathogenesis of increased albumin excretion and measurement of urine HS excretion may be helpful for studying metabolism in renal disease, especially in patients with minimal change lesions. PMID- 8513599 TI - Mesangial IgG in childhood minimal change disease: clinical relevance. AB - The clinical courses of five children with the nephrotic syndrome and renal biopsies diagnosed as minimal change disease (MCD) by light microscopy but with mesangial immune deposits of IgG (> or = 2+) and no dominant or codominant IgA were reviewed retrospectively to determine if the presence of significant mesangial deposits of IgG has prognostic implications and to evaluate the treatment these patients received. All five of the children were steroid dependent or resistant initially, and four received cyclosporine or cytotoxic agents later. After a mean follow-up period of 2.9 years for four and 20 years for one, all are in remission. All have normal renal function with no hypertension. These results suggest that the deposition of IgG in the mesangium of biopsies from patients with MCD by light microscopy may predict a more difficult course initially and may require more aggressive treatment to achieve permanent remission. PMID- 8513600 TI - Membranous nephropathy with severe tubulointerstitial and vascular changes in a patient with psoriatic arthritis treated with non-steroidal anti-inflammatory drugs. AB - We report on a patient who suffered from psoriasis vulgaris and psoriatic arthritis and developed nephrotic syndrome after long-term therapy with non steroidal anti-inflammatory drugs. Membranous nephropathy with tubulointerstitial and vascular (intimal hyperplasia) changes were found on renal biopsy using optical, immunofluorescent and electron microscopy. Treatment with methylprednisolone "pulse" therapy (1 g/24 h during 3 days) and continuing with prednisone 0.5 mg/kg/24 h was ineffective and end-stage renal failure developed 6 months after the diagnosis had been established. PMID- 8513601 TI - Symptomatic sulfadiazine crystalluria in AIDS patients: a report of two cases. AB - As the incidence of toxoplasma encephalitis (TE) in AIDS patients increases, sulfadiazine/pyrimethamine combination therapy is broadly administered. Two cases of acute and chronic renal sulfadiazine crystallization with acute renal failure and nephrolithiasis are reported. Controlled alkalinization of the urine and high fluid intake are recommended for prophylaxis of crystalluria. PMID- 8513602 TI - Spontaneous bilateral renal artery occlusion associated with chronic atrial fibrillation. AB - Bilateral renal artery occlusion with resultant anuria is a rare entity usually seen following blunt abdominal trauma. We present a case of bilateral renal artery occlusion in a patient with chronic atrial fibrillation who had complete resolution of acute renal failure following embolectomy 30 hours later although complete occlusion was shown by arteriography. After inclusion of this case with 35 other reported cases a point biserial correlation coefficient was calculated for delay in treatment (hours) vs outcome (functional or nonfunctional kidney and survival or death). There was no correlation between these parameters. The statistical results from these combined data demonstrate that attempts at reestablishing blood flow should be made without strict adherence to previously reported critical time frames, which have no applicability based on the evidence presented here. PMID- 8513603 TI - The influence of donor age on function of renal allografts from live related donors. AB - To assess the influence of donor age on renal allograft outcome, we retrospectively analyzed all 169 consecutive cyclosporine-treated live related donor kidney transplants, of whom 40 were HLA identical siblings. All recipients were similar with respect to demographic and immunologic characteristics. Incidence of rejection episodes and graft survival rates at 1 and 5-year posttransplant were independent of donor age. Best renal function, as assessed by the mean of the lowest 3 serum creatinine concentration levels in the first 2 months posttransplant correlated positively with donor age, particularly among HLA mismatched male recipients (r = 0.4, P < 0.002). Short and intermediate term renal function was inferior, but stable in the older donor recipient group when compared to the younger cohort. Mean serum creatinine levels at 5 years in recipients of kidneys from older donors (age > 55 years) was 2.6 mg/dl compared to 1.7 and 1.9 mg/dl in recipients of kidneys from donors between the ages of 18 39 and 40-54 years, respectively (P < 0.001). In view of the universal shortage of organs and the negligible morbidity to the donors, our results should not discourage the use of kidneys from elderly (age > 55 years) donors. PMID- 8513604 TI - Impact of time-interval after transplantation and therapy with fibrates on serum cholesterol levels in renal transplant patients. AB - It is unclear to what extent different immunosuppressive regimens contribute to increased serum cholesterol levels observed in renal transplant patients after prolonged periods of immunosuppression (i.e. 3 and 5 years following kidney grafting). Therefore 2 groups of renal transplant patients were evaluated with respect to serum cholesterol 3 years (n = 103) and 5 years (n = 66) after transplantation: Group 1: prednisone (Pred)/azathioprine (Aza) [3 years (y): n = 52; 5 y: n = 49; mean prednisone dose 12 +/- 1 mg/day]; group 2: cyclosporine A (CsA) alone or in combination with Pred (3 y: n = 51; 5 y: n = 17; prednisone dose 4 +/- 2 mg/day, p < 0.001 vs group 1). The groups were similar with respect to age, sex, body mass index, time interval after transplantation, underlying kidney diseases and concomitant drug therapy. Serum cholesterol levels were persistently higher in patients of group 2 when compared to group 1 (3 years: 7.3 +/- 0.2 vs 6.7 +/- 0.2 mmol/l, p < 0.01; 5 years: 7.5 +/- 0.1 vs 6.6 +/- 0.3 mmol/l, p < 0.01) despite 75% lower daily doses of Pred (p < 0.001) in CsA treated patients (group 2). Before transplantation, patients exhibited a similar distribution of serum cholesterol levels when compared to age, sex and body mass index matched healthy subjects. In contrast 3 and 5 years following transplantation 72% of the patients had serum cholesterol levels above 6.5 mmol/l, whereas in normal subjects, 60% had serum cholesterol levels below 6.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513605 TI - Tonsillar carcinoma in a renal graft recipient treated with cyclosporine A. AB - We report a right-sided tonsillar carcinoma in a 33-year-old renal graft recipient on cyclosporine A plus low dose prednisolone treatment. The patient had been a life-long non-smoker and alcohol abstainer. The undifferentiated rapidly growing tumour became manifest in the fifth year after transplantation. The clue to the early recognition of this aggressive tumour (T2N0M0G3) resulting in a hitherto favourable outcome after excision and irradiation above all lied in the alertness of the patient himself. PMID- 8513606 TI - Renal papillary necrosis in a hemodialysis patient. AB - We present the first case report of bilateral renal papillary necrosis developing in a patient on hemodialysis. A 37-year-old hypertensive male with chronic glomerulonephritis had a normal retrograde pyelogram one year prior to initiation of hemodialysis. After two years of maintenance dialysis, he presented with gross hematuria and was found to have extensive bilateral renal papillary necrosis. His only predisposing factor was hepatic cirrhosis. It is postulated that recurrent hypotensive episodes associated with hemodialysis may lead to renal papillary necrosis in predisposed individuals. This diagnosis should be considered in hemodialysis patients who develop hematuria. PMID- 8513607 TI - Recombinant human erythropoietin (rhEPO) treatment potentiates growth hormone (GH) response to growth hormone releasing hormone (GHRH) stimulation in hemodialysis patients. AB - On the basis of previously described effects of recombinant human erythropoietin (rhEPO) treatment on endocrine abnormalities present in uremia, we assessed the possible effect of treatment with rhEPO on growth hormone (GH) response to growth hormone releasing hormone (GHRH) in a group of uremic patients. Eight patients on maintenance hemodialysis for 12 to 228 months, not previously treated with rhEPO, were tested with 100 micrograms of GHRH i.v. in bolus before and after three months of rhEPO treatment (40 U/kg i.v. three times a week). Before treatment, the GH response to GHRH was characterized, in uremic patients, by remarkable differences in plasma GH values and in the pattern of response curve in single patients. The variability of GH response was not modified after rhEPO treatment; however, an overall potentiation of GH response with a significant increase of plasma GH (p = 0.017 at 15 min, p = 0.035 at 30 min after GHRH injection) was observed in the tests performed after treatment. rhEPO administration induced an evident improvement of anemia, blood hemoglobin concentration being 5.3-7.6 g/dl before and 9.1-11.3 g/dl after treatment; however a demonstrable correlation between the potentiation of GH response to GHRH and the increase of hemoglobin concentration was not observed. PMID- 8513608 TI - Association of interstitial lupus cystitis with systemic lupus erythematosus. PMID- 8513610 TI - The fetal brain: metabolic and circulatory responses to asphyxia. AB - The fetal environment is well suited for normal brain growth and development with oxygen availability well in excess of oxidative needs. With impairments in blood gas exchange, cerebral oxidative metabolism is initially maintained by an increase in cerebral blood flow, thus protecting the 'oxygen margin of safety', and, when this response becomes limited, by an increase in the brain's fractional extraction of oxygen. Additional adaptive mechanisms involve substrate alterations and a decrease in energy consuming processes, including growth restriction and behavioural state alterations. Although protective insofar as essential metabolic functions are maintained, pathologic change may become evident as the 'oxygen margin of safety' becomes limited or energy conserving measures give rise to abnormal growth and development. PMID- 8513609 TI - Granulocyte autoantibodies--markers for drug-induced autoimmune adverse effects. PMID- 8513611 TI - Magnetic resonance spectroscopy in hypoxic-ischemic encephalopathy. AB - In vivo magnetic resonance spectroscopy (MRS) allows repetitive, noninvasive measurement of cerebral metabolites, including ATP, phosphocreatine (PCr), inorganic phosphate (Pi), intracellular pH, lactate, and N-acetyl aspartate. MRS has been used extensively to study cerebral metabolic changes in neonatal neurologic disorders. In babies with severe hypoxic-ischemic encephalopathy, PCr decreases and Pi increases, causing a fall in PCr/Pi and PCr/ATP, and a rise in Pi/ATP. These changes correlate with neurodevelopmental outcome. Decreased ATP is only seen in extremely severe hypoxic-ischemic encephalopathy and is usually associated with death in the neonatal period. Serial MRS studies may be helpful in selecting babies who would benefit from interventional treatment. Ongoing advances in MRS technology will permit localized, multinuclear spectroscopy, improving our ability to identify cerebral metabolic changes. PMID- 8513612 TI - Cellular alterations associated with perinatal asphyxia. AB - Asphyxia triggers a cascade of cellular biochemical events that lead to temporary alterations in cellular function and/or cell death. Tissue hypoxia and ischemia lead to depolarization of neuronal membranes, alteration in cellular ion homeostasis and changes in energy metabolism. The changes are accompanied by enhanced release and diminished re-uptake of neurotransmitters, including the excitatory amino acid glutamate. Abnormal accumulation of calcium in neurons is produced by several factors, including opening of voltage-sensitive calcium channels, activation of excitatory amino acid-mediated ion channels, diminished pumping of calcium out of neurons, and increased release of free calcium from the endoplasmic reticulum. Elevated intracellular calcium levels appear to kill cells by activation of proteases, lipases, protein kinase C, and generation of free radicals. These factors act synergistically over minutes to hours to produce cellular necrosis. Current research is directed at defining the relative contribution of these steps to cell death and to devising therapeutic strategies to salvage brain tissue. PMID- 8513613 TI - Relationship of fetal asphyxia to neuropathology and deficits in children. AB - Neuropathological studies suggest that the majority of the fetal asphyxial complications resulting in brain damage in either preterm or term fetus occur before the onset of labor. Anoxia because of the rapid sequence of events will usually result in death of the fetus. Hypoxia of 1-3 h duration may account for brain damage and deficits in children who survive. The threshold for brain damage is a severe acidosis with a pH < 7.0 in conjunction with systemic hypotension. The prevalence of antepartum fetal asphyxia and the frequency of deficits in such children have not been established. The prevalence of intrapartum fetal asphyxia determined biochemically is 2%. The majority of these children develop normally because of fetal cardiovascular compensatory mechanisms which protect the brain. However, beyond the threshold of asphyxia in either the preterm or term fetus, neuropathology may develop leading to deficits in some children. PMID- 8513614 TI - The predictive significance of clinical measures of brain injury in the newborn. AB - Detailed neurological assessment is of major importance for the accurate diagnosis and prediction of outcome of acute hypoxic-ischemic encephalopathy in the term newborn. Because the clinical features of hypoxic-ischemic encephalopathy are nonspecific, the diagnosis of hypoxic-ischemic cerebral injury should be made with caution and only in the context of historical evidence of intrapartum hypoxic-ischemic insult. In the term newborn, the absence of encephalopathy during the first days of life essentially precludes the occurrence of a significant acute intrapartum hypoxic-ischemic insult as the primary etiology of longterm neurological abnormalities. However, hypoxic-ischemic cerebral injury which originates earlier in gestation may result in few, if any, clinical abnormalities during the newborn period. In premature newborns and term infants on complex life support apparatus, neurological examination during the first days of life is of limited prognostic value. In these instances, greater reliance must be placed on other investigations, e.g. neuroimaging, neurophysiological techniques, and biochemical derangements. PMID- 8513615 TI - Epidemiological principles for the evaluation of monitoring programs--the Dublin experience. AB - There is no gold-standard measurement for 'fetal asphyxia'; methods of fetal surveillance must therefore be evaluated in the context of a management program that includes clinical intervention when a diagnosis of 'fetal compromise' is made. The use of non-randomized comparison groups is prone to major bias which can only be avoided satisfactorily by random assignment of alternative monitoring policies. To avoid being misled by random errors, randomized controlled trials must be surprisingly large. The hypothesis, generated from the results of four small trials (total of 2,000 women), that more intensive intrapartum monitoring reduces the risk of neonatal seizures, was tested and sustained in the larger Dublin trial (13,000 women). Early-onset neonatal seizures now provide the best validated epidemiological index of obstetrically-preventable intrapartum asphyxia at or after term. Paediatric follow-up at age 4 failed to identify any beneficial effect of intensive monitoring on cerebral palsy, despite the protective effect on neonatal seizures. The results of the Dublin trial are consistent with those of comparable trials, and this enhances the generalizability of the study's results. PMID- 8513616 TI - Electronic fetal monitoring and later outcome. AB - The principal rationale for the almost universal use of electronic fetal monitoring (EFM) in labor is that its use can effectively prevent the full expression of brain-damaging birth asphyxia by timely intervention in labor. This central hypothesis of EFM has never been adequately tested, in part because of the difficulty of obtaining a large enough sample. However, for this hypothesis to be true, 3 simpler conditions must be met. The first is that EFM be reliable, i.e., that substantial inter-observer agreement exist as to the identity and meaning of EFM patterns. The second is that EFM be valid, i.e., that one or more EFM patterns be statistically associated with the adverse neurological outcome to be prevented. The third condition is that if EFM and adverse outcome are related, the association is causal. A review of the literature indicates that none of these 3 conditions has been met thus far. Future research should concentrate on establishing the reliability and validity of specific EFM patterns; only those patterns truly predictive of adverse outcome and detectable by most practitioners are worth considering as indicators for intervention in labor. PMID- 8513617 TI - The relationship between heart rate and asphyxia in the animal fetus. AB - In order to understand the mechanisms which regulate and control basal heart rate as well as heart rate variability in the fetus, a number of studies have been conducted in fetal animals. Information has been obtained largely from fetal sheep during the last third of gestation, although recently investigators have directed their attention to earlier gestations, such as 80-90 days, with term in the sheep being 145 days. A few studies have focused on the non-human primate fetus for additional information. A variety of techniques has been utilized experimentally to produce hypoxemia and/or acidemia in fetal animals, including umbilical cord compression, maternal hypoxemia, and uterine blood flow restrictions. Evidence to date would indicate that both chemoreceptors and baroreceptors are present and active in the late gestation sheep fetus, giving rise to acute changes in fetal heart rate (FHR) with changes in oxygenation. Factors which must be considered in interpreting alterations in both mean FHR and FHR variability in response to a decrease in oxygenation include: 1) the mechanism giving rise to decrease in oxygen delivery, 2) the duration of hypoxemia and/or asphyxia, 3) the effect of sleep states and behavioural activity, 4) gestational age, and 5) condition of the fetus prior to the decrease in oxygen delivery. Heart rate variability in fetal sheep has been studied extensively and it has been shown that accelerations in the FHR are closely associated with skeletal muscle activity much like the human fetus, suggesting similar control mechanisms in the 2 species. The late gestation sheep fetus consistently and reliably experiences an increase in heart rate variability with acute hypoxemia with and without acidemia until severe acidosis develops. In contrast, the hypoxemic human fetus, prior to labour, generally exhibits a decrease in FHR variability. The explanation for this apparent species difference remains unclear. PMID- 8513618 TI - The causes of cerebral palsy. Recent evidence. AB - Cerebral palsy (CP), unlike many other neurodevelopmental disorders, is associated with abnormalities of pregnancy and birth, particularly 'birth asphyxia' and low birthweight. Associations, however, need not be causal, and some prenatally damaged infants manifest clinical signs suggestive of birth asphyxia in the perinatal period. The lack of a clinically reliable indicator of impaired fetal-placental gas exchange limits our confidence that birth asphyxia plays a true causal role in cerebral palsy. Premature delivery is the single most important antecedent of cerebral palsy, and the increase in survival of very small infants resulting from newborn intensive care may augment this contribution in the future. Cranial ultrasound imaging can describe patterns of neonatal brain damage in the low birthweight infant that are highly predictive of later cerebral palsy. Future research on the causes of cerebral palsy may benefit from improvements in the neurological assessment of the fetus prior to labor and from a clearer understanding of the role of endocrine factors, particularly thyroid disorders, in neurologic development. PMID- 8513619 TI - Drug abuse in pregnancy. PMID- 8513620 TI - The process of addiction. PMID- 8513621 TI - The epidemiology of alcohol, marijuana, and cocaine use among women of childbearing age and pregnant women. AB - Although most women report alcohol use, women generally are light drinkers. Those who drink and drink heavily are more likely to be young, white, single, to have a higher education and income, and to be employed outside the home. However, women who drink during pregnancy, and particularly, those who continue to drink through the third trimester are different. They are older, more likely to be black, and they have higher rates of illicit drug use, less education, and lower social status. Marijuana and cocaine are used less frequently. However, women of childbearing age have the highest rates of use for both these drugs. Women who use marijuana during pregnancy are more often black, unmarried, and of lower social class. Cocaine users tend to be black, older, unmarried, and also of lower socioeconomic status. Both groups more frequently use other illicit drugs and, in general, receive less prenatal care. Therefore, for alcohol, marijuana, and cocaine, the highest rates of use are found among women of childbearing age. The women most likely to use substances during pregnancy are women who also have other characteristics that are, in themselves, significant risk factors for poor pregnancy outcome. These covariates must be considered in the evaluation of the effects of prenatal substance use. PMID- 8513622 TI - Kinetics of drug transfer to the fetus. AB - Experimental studies in animal models have contributed significantly to our understanding of the pharmacokinetics of drug disposition in the maternal-fetal unit. This chapter has considered some of the factors that are important in determining the extent of fetal exposure to drugs that are consumed by the mother during pregnancy. A knowledge of the maternal-fetal pharmacokinetics of the drugs of abuse will help provide a better understanding of the limitations of the current methods used in perinatal drug screening and in the interpretation of the results. PMID- 8513623 TI - Impact of prenatal alcohol exposure on the newborn and the child. AB - Maternal use of alcohol during gestation is associated with FAS and less severe problems in exposed children, such as FAE and ARBD. This article reviewed the literature concerning the status of affected and exposed neonates and the available information on the developmental course of infants and children. Physical and behavioral characteristics of gestational alcohol exposure were described, and outcomes of retrospective and prospective research were reviewed. Currently, it is evident that heavy use and bingeing are associated with an increased risk to the offspring across a range of outcomes. Although the last 20 years of research in this area have provided a great deal of information, there remain unanswered questions regarding the course of the affected individual over the lifespan, the neuropsychologic status of children, and the relationship of prenatal exposure and the caregiving environment to the observed outcomes. PMID- 8513624 TI - Maternal, placental, and fetal pathophysiology of cocaine exposure during pregnancy. AB - As should be evident from the case reports, epidemiology studies, and animal data, the primary mode of cocaine action is vasoconstriction, whether it occurs on the maternal side or the fetal side of the placenta. Attempts to characterize the fetal effects of cocaine exposure during pregnancy in order to formulate a "fetal cocaine syndrome" has revealed a wide spectrum of fetal effects. Therefore, a well-defined "fetal cocaine syndrome" does not exist. In fact, most fetal defects may be related to vasoconstriction, hypertension, and infarcts at any time during gestation and in any structure. Even the issues of SIDS and seizures may be the result of clinically undetectable vasospasm or hemorrhages. Traditional dogma dictates that a teratogen interferes with normal development of a structure such that the structure is missing, malformed, or dysfunctional. Moreover, since individual structures are formed at specific times during development, these structures are vulnerable to injury at these "time windows." Classical teratogens exert their damaging effects during the organogenesis period. For cocaine, however, exposure during any period in gestation may place any organ or structure at potential risk for damage. While repeated exposures during pregnancy may increase the risk of cocaine-induced damage, it appears that even a single exposure may produce infarction, edema, and tissue necrosis. The site of damage may be related to the tissue level of cocaine and the weakness of the blood vessels at that site. Subsequent loss of vascular supply and tissue necrosis produce fetal damage that is beyond capacity for repair. PMID- 8513625 TI - Cocaine, heroin, and phencyclidine: obstetric perspectives. PMID- 8513626 TI - The impact of prenatal marijuana and cocaine use on the infant and child. AB - The prevalence of cocaine use by pregnant women has been estimated by various researchers to range from 8-17%. Women who use cocaine during pregnancy are usually older and black and use more of other drugs. The effects of prenatal cocaine use on a variety of outcomes have not been substantiated. For each outcome discussed, there are as many reports of no effects as there are reports of detrimental effects. The studies that indicate that there are no effects of exposure are generally more sound methodologically. It is also possible that there are additional investigations of prenatal cocaine use that have not been published because of the hesitancy to publish reports in which no effects have been found. The findings regarding obstetric complications are equivocal. Although some investigators have demonstrated significant effects of cocaine use during pregnancy, particularly on abruptio placentae, many of these relationships disappear when factors such as prenatal care and polydrug use are assessed. The same pattern can be noted for the effects of prenatal cocaine exposure on gestational age, growth, and morphology. Significant effects of prenatal cocaine use on these outcomes have been reported by some investigators. However, these results are found generally in studies where poly-drug-cocaine users are compared with non-drug-using women. Such comparisons do not control adequately for other factors in the lifestyles of the cocaine-using woman. There are few significant differences when the offspring of cocaine-using women are compared with those of women who use other drugs. It is difficult to evaluate the effects of prenatal cocaine use on either neonatal neurobehavioral outcomes or on long-term growth and development because of the insufficient number of studies and the equivocal findings. Longitudinal studies are needed to disentangle the effects of cocaine use from the effects of the lack of prenatal care, polydrug use, and the increased risks associated with a drug-using life style. PMID- 8513627 TI - Prenatal exposure to tobacco and marijuana: effects during pregnancy, infancy, and early childhood. PMID- 8513628 TI - History taking and substance abuse counseling with the pregnant patient. PMID- 8513629 TI - Critical components of obstetric management of chemically dependent women. AB - Providing prenatal care to chemically dependent women presents multiple dilemmas and challenges to clinicians. It is a complex task and one that is incongruent with the usual perceptions of the obstetric experience. However, it must be viewed as an opportunity to bring these alienated women into the health care system. Pregnancy represents a period in most women's lives when they recognize the need for and are receptive to caring and responsive intervention. By optimizing the prenatal experience of chemically dependent women, maternal-fetal outcomes will be improved and the groundwork laid for the ongoing therapeutic services that are needed to maintain the health and well-being of the mother and child. PMID- 8513630 TI - Controversies in the management of adnexal masses. PMID- 8513631 TI - Relationship of macroscopic appearance to the histologic diagnosis of ovarian tumors. PMID- 8513632 TI - Sonographic patterns of ovarian tumors. PMID- 8513633 TI - Conservative management of small postmenopausal cystic masses. PMID- 8513634 TI - Laparoscopic surgery for ovarian lesions: potential pitfalls. AB - Laparoscopic surgery for ovarian lesions has the potential for an enormous positive impact on the care that we are able to provide for our patients. Technologic advances and the proliferation of new equipment have occurred at a rapid rate. However, the criteria for the safe and appropriate use of endoscopic surgery have not been developed fully or followed by all surgeons, and there is some evidence that a lack of adherence to carefully considered protocols has the potential to have an adverse impact on women with ovarian lesions. McDonough made a thoughtful presentation on the need for technology assessment in the reproductive sciences, focusing on the fact that there has been a rapid diffusion of technology without prior broad-based critical peer review and stressing the need to have scientific technology assessment. Pitkin, in his editorial on operative laparoscopy, questioned whether we are evaluating therapeutic appropriateness properly as a separate and independent issue from technical feasibility. Obviously, it would be preferable to have had more controlled prospective data on the relative merits and risks of the use of the laparoscope for resection of ovarian cysts before the widespread use of this technology. However, there are several situations in which it currently appears to have important clinical utility for the patient. In addition, it already is being used widely, and it would be inappropriate to withhold this method from our patients. However, it should be urged that careful prospective evaluation be undertaken so that both the scientific community and the public are able to have an accurate understanding of the risks, benefits, indications, and contraindications of this technology. In addition, when a surgeon is considering pelviscopic surgery for an ovarian mass, it is essential that this be done with strict adherence to carefully constructed preoperative criteria and intraoperative protocols. PMID- 8513635 TI - Management of the adnexal mass by operative laparoscopy. PMID- 8513636 TI - Ultrasound screening in women at risk for ovarian cancer. AB - As no unobjectionable study has yet been published on ovarian cancer screening with ultrasound and/or tumor markers in the general population or in risk groups, it is not possible to determine if screening would decrease the mortality in ovarian cancer. Because the medical gain is unclear, the cost per life gained can not be estimated. At present, there is not sufficient scientific evidence to recommend screening for ovarian cancer with any method. It may be worthwhile to perform a large randomized trial to discover if early detection is of value, as ultrasound is already being used on a large scale in asymptomatic women in order to detect ovarian cancer. Such a study will also gain knowledge about the early stages of ovarian cancer. Moreover, methods for investigation of lesions detected by ultrasound (i.e., color Doppler and puncture) could be evaluated. Only through a large-population study would we be able to know if prophylaxis for ovarian cancer (oral contraceptives) is more efficient than screening. Studies on lung cancer have shown that persuading people to stop smoking more effectively decreases the mortality of lung cancer than screening. A population study would be a giant enterprise, but probably the only way to determine whether screening for ovarian cancer with ultrasound is of any value. The following attitude to ultrasound examination in risk groups is proposed as long as the value of screening is unclear: Women with hereditary ovarian cancer (one or two first degree relatives with ovarian cancer) should be made aware of the risks, and regular ultrasound check-ups seems advisable for psychologic reasons and because the risk for cancer is high. The surveillance proposed by Lynch seems reasonable: ultrasound at least once a year, possibly in combination with CA-125, and discussion concerning surgical removal of the ovaries after childbearing is complete or around 40 years of age. The protective effect of oral contraceptives should be emphasized. Women at risk should be made aware of the fact that mesothelial cancer can develop even after ovarian removal. If possible, these women should be registered and their family history noted. Thus, their risk of contracting ovarian cancer can be estimated and compared to the outcome when the ovaries are removed. Mesothelial cancers after oophorectomy must be noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513637 TI - Progress in the management of tuboovarian abscesses. AB - The last 20 years have witnessed remarkable improvements in the treatment of tuboovarian abscesses. Gone are the days of significant mortality associated with ruptured and unruptured TOAs. Broad-spectrum antibiotics have enabled patients to be treated solely with medical therapy, avoiding the need for surgery. Operative intervention is still necessary in 25% of cases of unruptured TOAs, but the combination of conservative surgical procedures, such as unilateral salpingo oophorectomy, and broad-spectrum antimicrobial agent therapy have reduced the need for total abdominal hysterectomy with bilateral salpingo-oophorectomy greatly. Although fertility after TOAs is compromised significantly, new advances in reproductive technology, including in vitro fertilization and donor egg transplantation, represent reproductive options for these women. Percutaneous drainage and laparoscopic treatment of TOAs are becoming popular treatment options, but prospective studies urgently are needed to assess their efficacy. PMID- 8513638 TI - Contemporary radiologic percutaneous abscess drainage in the pelvis. AB - In summary, PAD of pelvic abscesses is an established radiologic procedure. The procedure has gained wide acceptance as an adjunct in the management of patients with pelvic abscess. The procedure involves minimal trauma, is well tolerated, and produces early relief of symptoms. In many instances, it may shorten the length of the hospital stay, reduce costs, and often eliminate the need for surgical intervention. In selected patients, PAD may serve as a temporizing measure in a critically ill or endstage patient. Initial results of PAD treatment of TOA are encouraging, suggesting that this procedure, just as elsewhere in the abdomen, is safe and effective, but larger series are required and long-term follow-up is necessary for evaluation of the cure rate, rate of recurrence, and possible complications. PMID- 8513639 TI - Routine antenatal screening and prenatal diagnosis of vertically transmissible infection. PMID- 8513640 TI - Toxoplasmosis in pregnancy. AB - Primary infection with Toxoplasma gondii in pregnant women occurs all over the world with frequencies between 0.1-1%. In approximately 40% of the cases, the unborn child is infected. The risk of fetal infection increases during pregnancy, while at the same time the risk of severe disease decreases. As a result, infants with congenital toxoplasmosis are mostly asymptomatic at birth, but long-term studies indicate that up to 85% of them will develop sequelae including chorioretinitis (leading to severe impairment of vision), hearing loss or mental retardation. Early recognition of maternal infection and treatment with spiramycin or pyrimethamine-sulphadiazine will reduce the parasitic colonization of the placenta by more than 60% and prevent infection in the fetus. If fetal infection has already occurred, maternal treatment modifies the fetal disease. Therapy during the first year of life improves the prognosis. It is possible today to identify infected fetuses by prenatal diagnosis based on detection of the parasite in cord blood, amniotic fluid and placental tissue. Specific antibodies and non-specific signs of infection in fetal blood give additional information. Advances in laboratory techniques have made it feasible to consider serological surveillance of pregnant women. The present recommendation is that each country should provide data on the incidence of toxoplasma infection in pregnancy and thereby decide whether it represents a problem and what measures should be adopted. This paper summarizes the present knowledge of the parasite and its implication for the mother and unborn child. The effect and problems of primary and secondary prevention in pregnancy are discussed as well as the efficacy of treatment. The need for future research including long-term follow-up studies are emphasized. PMID- 8513641 TI - Female genital tract discharge. PMID- 8513642 TI - Infertility as an infectious disease--epidemiology and prevention. PMID- 8513643 TI - Prophylactic antibiotics and prevention of surgical sepsis. PMID- 8513644 TI - Infection due to Chlamydia trachomatis in pregnancy and the newborn. AB - Bacteria in the genus Chlamydia comprise three species, C. trachomatis, C. psittaci and C. pneumoniae. C. trachomatis infection is common, varying in prevalence in women from 0% to 37%. In the United States, the prevalence rate is estimated currently to be about 5%. Pregnancy may predispose to an increased chance of infection with C. trachomatis, through physiological immunosuppression and/or cervical ectopy. Maternal antibodies to C. trachomatis provide limited, if any, protection for the newborn. C. trachomatis causes pelvic inflammatory disease--which can result in tubal infertility or ectopic pregnancy and postabortal or late postpartum endometritis. It may also cause chorioamnionitis and premature delivery of the fetus. The incidence of vertical transmission of chlamydiae from mother to baby varies; if the mother is untreated, 20-50% of the newborns will develop conjunctivitis and 10-20% will develop pneumonia. C. psittaci infection in pregnancy is rare, but can cause spontaneous abortion. Whether C. pneumoniae infection in pregnancy has any influence on the outcome has not been ascertained. C. trachomatis can be detected by one or more of several methods; enzyme immunoassays are the least sensitive, but the most widely used. Screening for C. trachomatis in pregnancy may be of benefit in areas of high prevalence, and is generally regarded as being cost-effective if the prevalence rate is more than 5%. Pregnant women are best treated with erythromycin, 250 mg four times daily for 7 days. This will prevent infection of the newborn in more than 90% of cases. The infected neonate should be treated with erythromycin, given systemically and also with topical tetracycline if conjunctivitis is present. PMID- 8513645 TI - Chorioamnionitis and pre-term delivery. PMID- 8513646 TI - Human immunodeficiency virus infection in pregnancy. AB - Human immunodeficiency virus (HIV) infection in women is an increasing problem. World wide, at least 25% of all infections occur in adolescent or adult women, most of whom are of child-bearing age. The commonest modes of acquisition of HIV infection are sexual contact with an HIV-infected male and sharing needles during injecting drug use. Vertical transmission is the major route of HIV infection in infants and children and can occur in utero, intrapartum, through exposure to infected blood or secretions, or post partum, via breast milk. HIV infection has not been demonstrated to affect fertility, or to influence the outcome of pregnancy unless there is evidence of significant immune dysfunction, with CD4 counts below 400/mm3. Though data are limited, pregnancy does not appear to affect the course of HIV infection. Low CD4 counts predispose women to the opportunistic infectious complications of HIV. Pathogens include Candida sp., Mycobacterium tuberculosis, Pneumocystis carinii, Toxoplasma gondii, Cryptococcus neoformans and Cryptosporidium. These pathogens require early recognition and diagnosis if optimal treatment and outcome are to be attained. Treatment with zidovudine and prophylaxis against Pneumocystis carinii are appropriate when CD4 counts are less than 200/mm3, though the safety of zidovudine in early pregnancy is not known. Similarly it is not known whether zidovudine treatment of the mother prevents transmission of HIV infection to her baby. Caesarean section does not prevent peripartum transmission of HIV and should be undertaken only for other appropriate indications. The utility of antenatal screening for HIV depends upon the seroprevalence in the population. Such programmes must be supported by comprehensive clinical care as well as sensitive and non-judgemental counselling. PMID- 8513647 TI - Plasma protein binding and pharmacological response. PMID- 8513648 TI - Comparative pharmacokinetics of the newer antiepileptic drugs. AB - During the past few years a major increase has taken place in the number of drugs which have become available in the antiepileptic arsenal. In fact, 3 new antiepileptic drugs, vigabatrin, oxcarbazepine and lamotrigine, were recently approved in several European countries. Two other drugs, felbamate and gabapentin, are expected to be approved in the US in the near future. This review comparatively evaluates the pharmacokinetics of the following 10 new antiepileptic drugs: felbamate, flunarizine, gabapentin, lamotrigine, oxcarbazepine, remacemide, stiripentol, tiagabine, topiramate and vigabatrin. Three of the new drugs, gabapentin, topiramate and vigabatrin, are more promising on the basis of their pharmacokinetic features. They are well absorbed, excreted mainly unchanged in the urine, and are not susceptible to enzyme induction or inhibition. Their drug interaction potential appears to be minimal. About 50% of felbamate is excreted unchanged, with the rest eliminated by metabolism. The remaining drugs are eliminated by metabolic processes such as glucuronidation (lamotrigine), deglycine formation (remacemide) or oxidative metabolism (flunarizine and stiripentol). Oxcarbazepine and remacemide have high hepatic clearance and are biotransformed to hydroxy and deglycine metabolites, respectively, with the activity of their metabolites contributing to the antiepileptic activity of the parent drug after oral administration, despite high first-pass effect metabolism. Gabapentin and oxcarbazepine do not behave pharmacokinetically as their original design intended. Gabapentin is not effective as a chemical drug delivery system for gamma-aminobutyric acid (GABA), and oxcarbazepine serves as a prodrug to its hydroxy metabolite, but does not act as a drug on its own. Nevertheless, these 2 agents demonstrate efficacy in extensive preclinical and clinical trials. Although the pharmacokinetics features of these drugs are important, these features are secondary to their pharmacodynamic properties--i.e. to the requirement that new antiepileptic drugs have to have proven clinical efficacy and safety in epileptic patients. PMID- 8513649 TI - Clinical pharmacokinetics of alprazolam. Therapeutic implications. AB - Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by hepatic microsomal oxidation, yielding alpha-hydroxy- and 4-hydroxy-alprazolam as principal initial metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma concentrations of the 4-hydroxy metabolite exceed those of the alpha-hydroxy derivative, but urinary recovery of alpha-hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be explained by chemical instability of 4-hydroxy-alprazolam in vitro. After single 1 mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a peak plasma concentration 12 to 22 micrograms/L occurring 0.7 to 1.8h postdose, a volume of distribution of 0.8 to 1.3 L/kg, elimination half life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg. Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-independent and are unchanged during multiple-dose treatment. On average, mean steady-state plasma alprazolam concentrations change by 10 to 12 micrograms/L for each daily dosage change of 1 mg/day. Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender. Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced by the phase of the menstrual cycle in women. Coadministration of cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs alprazolam clearance. However, alprazolam clearance is not altered by coadministration of propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance may be impaired if alprazolam is coadministered. Alprazolam does not alter the pharmacokinetics of digoxin. Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 micrograms/L. Concentrations higher than this may be needed for suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness, sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in frequency with higher steady-state plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513651 TI - Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations. AB - Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined. PMID- 8513652 TI - The effectiveness of teaching clinical pharmacokinetics by computer. PMID- 8513653 TI - Differential effects of ACE inhibiting drugs: evidence for concentration-, dose-, and agent-dependent responses. PMID- 8513654 TI - The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. AB - Terfenadine is rapidly and nearly completely biotransformed during a first pass to an active acid metabolite. Accumulation of unmetabolized terfenadine has been associated with altered cardiac repolarization. Drug-drug interactions resulting in the accumulation of terfenadine have been reported for ketoconazole and erythromycin. Six subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral fluconazole (200 mg once daily). The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole. Unmetabolized terfenadine was not present in any subject, and cardiac repolarization was not significantly changed from baseline during any phase of the study. We conclude that a pharmacokinetic interaction between terfenadine and fluconazole exists; however, the absence of accumulation of parent terfenadine in plasma suggests that a clinically significant interaction is unlikely. PMID- 8513650 TI - Cyclosporin clinical pharmacokinetics. AB - Cyclosporin is a powerful immunosuppressive drug used in transplantation medicine and to treat autoimmune diseases. It is a lipophilic molecule, with its bioavailability dependent on food, bile and other interacting factors. Cyclosporin is extensively metabolised in the liver by the cytochrome P450 3A system, which is subject to considerable interindividual variation. Distribution of cyclosporin depends not only on physicochemical characteristics, but also on biological carriers such as lipoproteins and erythrocytes in blood. Cyclophilin, a binding protein for cyclosporin, influences distribution of cyclosporin in the body. Despite its lipophilicity, cyclosporin does not appear in the brain. The distribution of metabolites in the body can differ from that of cyclosporin itself. Elimination of the drug is mainly via the bile as metabolites, other routes not being very important. Pharmacokinetic parameters of cyclosporin are highly variable and depend on factors such as age, the physical condition of the patient, type of organ transplant or comedication. Renal side effects of cyclosporin are dose-related, but the influence of the dosage regimen has not been thoroughly investigated. An important factor in the reported variability is the different analytical methods used. Following the recommendations of recent consensus documents to monitor blood concentrations, this source of variability may diminish in the future. Several metabolites are reported as having less immunosuppressive activity than the parent drug. Metabolites with renal side effects have been reported. These and other effects of metabolites have not been clearly defined in the literature, presumably because of the highly variable activity of cyclosporin-metabolising liver enzymes and the paucity of data available on metabolite pharmacokinetics. The therapeutic range and dosage of cyclosporin are therefore highly dependent on many individual parameters in patients. Dosages of less than 5 mg/kg/day, however, rarely cause renal side effects. Further studies to correlate the clinical pharmacokinetics of metabolites with their activity and adverse effects are needed. PMID- 8513655 TI - Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. AB - Grapefruit juice produces a marked and variable increase in felodipine bioavailability. The pharmacokinetics of felodipine and its single primary oxidative metabolite, dehydrofelodipine, were studied after drug administration with 200 ml water, grapefruit juice, or naringin in water at the same concentration as the juice in a randomized crossover trial of nine healthy men. With grapefruit juice, mean +/- SEM felodipine area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were 206% +/- 23% (range, 123% to 330%, p < 0.01) and 170% +/- 24% (range, 127% to 310%, p < 0.02), respectively, compared with water. Dehydrofelodipine/felodipine ratios for AUC (1.5 +/- 0.2 versus 2.2 +/- 0.2, p < 0.001) and felodipine Cmax (1.5 +/- 0.2 versus 2.2 +/- 0.2, p < 0.001) were reduced, consistent with inhibition of presystemic felodipine metabolism. Intersubject changes in felodipine and dehydrofelodipine AUC supported inhibition of both primary and secondary metabolic steps as a mechanism. The interaction could not be predicted from baseline pharmacokinetics with water and did not result in more consistent bioavailability among individuals. Naringin solution produced much less of an interaction, showing that other factors were important. PMID- 8513656 TI - Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1. AB - Disulfiram and its reduced metabolite diethyldithiocarbamate have been identified previously as selective mechanism-based inhibitors of human liver microsomal cytochrome P450 2E1 in vitro. In animals, a single oral dose of disulfiram has been shown to produce a rapid and selective inactivation of hepatic P450 2E1 content and catalytic activity in vivo. This investigation explored the efficacy of single dose disulfiram as an inhibitor of human P450 2E1 activity in vivo. Clinical P450 2E1 activity was assessed by the 6-hydroxylation of chlorzoxazone, a metabolic pathway catalyzed selectively by P450 2E1. Six healthy volunteers received 750 mg oral chlorzoxazone on two occasions in a crossover design, 10 hours after 500 mg oral disulfiram, or after no pretreatment (control subjects). Disulfiram pretreatment markedly decreased chlorzoxazone elimination clearance to 15% of control values (from 3.28 +/- 1.40 to 0.49 +/- 0.07 ml/kg/min, p < 0.005), prolonged the elimination half-life (from 0.92 +/- 0.32 to 5.1 +/- 0.9 hours, p < 0.001), and caused a twofold increase in peak plasma chlorzoxazone concentrations (20.6 +/- 9.9 versus 38.7 +/- 10.3 micrograms/ml, p < 0.001). Disulfiram also profoundly decreased the formation clearance of 6-hydroxychlorzoxazone, from 2.30 +/- 0.93 to 0.17 +/- 0.05 ml/kg/min (p < 0.005). These findings show that a single dose of disulfiram significantly diminishes the activity of human P450 2E1 in vivo. The efficacy of single-dose disulfiram as an inhibitor of human P450 2E1 suggests that this modality for manipulating clinical P450 2E1 activity may provide a useful probe for delineating P450 2E1 participation in human drug biotransformation or for the treatment of poisoning by P450 2E1-activated toxins. PMID- 8513657 TI - Michaelis-Menten kinetics determine cyclosporine steady-state concentrations: a population analysis in kidney transplant patients. AB - Dosage adjustments of cyclosporine are confounded with an unexpected degree of variability, thus invalidating a direct proportionality between the oral dose rate and the steady-state concentration. In 1033 observations of dose rate and average steady-state concentration collected during therapeutic monitoring (area under the curve method) in 134 adult kidney transplant patients, a population pharmacokinetic analysis showed that a Michaelis-Menten model fitted the data better than a linear clearance model. It was further shown that the Michaelis Menten constant (Km) parameter of the Michaelis-Menten model (the average steady state concentration at half-maximal dose rate) increased during the first 4 months after transplantation whereas the maximal dose rate of the Michaelis Menten model (Vmax) remained constant. The following parameters with interindividual variation in parenthesis were estimated: Vmax = 852 mg/24 hr (43%) and Km at 114 days after transplantation = 349 ng/ml (117%). An algorithm was derived from this population model that guides the clinician during the adjustment of oral cyclosporine dose rates. PMID- 8513658 TI - Amrinone-associated thrombocytopenia: pharmacokinetic analysis. AB - Amrinone-associated thrombocytopenia is thought to result from nonimmune-mediated peripheral platelet destruction. Platelet destruction may be a concentration dependent toxic effect of amrinone or its principal metabolite N-acetylamrinone. Eighteen children receiving amrinone after heart surgery were prospectively evaluated to correlate the pharmacokinetics of amrinone and N-acetylamrinone with thrombocytopenia. Amrinone and N-acetylamrinone plasma concentrations were determined by HPLC during loading, infusion, and terminal elimination, with concurrent monitoring of platelet counts. Thrombocytopenia developed in eight patients (platelet count, 66 +/- 17 x 10(9) platelets/L [mean +/- SD]). Peak and steady-state amrinone plasma concentration, amrinone total dose, duration of amrinone exposure, and amrinone area under curve (AUC) were similar between patients with and without thrombocytopenia. N-Acetylamrinone peak concentration, steady-state concentration, N-acetylamrinone AUC, and ratio of N-acetylamrinone to amrinone were greater in patients with thrombocytopenia. This association suggests that N-acetylamrinone, and not amrinone, may be the mediator of thrombocytopenia in children receiving amrinone. PMID- 8513659 TI - Attenuation of the gastric acid and serum gastrin-lowering effects of the prostaglandin E2 analog enprostil. AB - Enprostil, a synthetic prostaglandin E2 analog, has been shown to decrease gastric acid secretion and plasma gastrin levels during short-term treatment. However, effects of prolonged treatment with enprostil on these parameters in humans are unknown. We have studied the effects of 35 micrograms enprostil twice daily on 24-hour intragastric pH, basal gastrin, and meal-stimulated gastrin release in 10 healthy volunteers. Enprostil, 35 micrograms, was ingested twice daily for 4 weeks. Subjects were studied on day 0 (preentry) and days 1 and 29, when enprostil was taken 30 minutes before the first and third standard test meals at 9 AM and 5 PM. Enprostil significantly increased 24-hour median pH (p < 0.02) on day 1 but not on day 29. Enprostil had no significant effect on basal gastrin levels compared with placebo. However, on day 1, but not on day 29, postprandial gastrin levels were significantly lower compared with preentry (p < 0.05). On day 29 post-prandial gastrin levels after the second standard test meal were significantly higher compared with preentry data (p < 0.05). In conclusion, 35 micrograms enprostil twice daily reduced gastric acidity and serum gastrin levels on the first day of treatment, but this effect attenuated and even transiently reversed during a 4-week treatment period. PMID- 8513661 TI - Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease. AB - OBJECTIVE: To assess the value of serum measurements of tacrine hydrochloride and its metabolite in predicting risk of adverse reaction in Alzheimer's disease. METHODS: The study was an outpatient-based controlled clinical trial. Study subjects were 35 female and 31 male patients who were receiving 50 to 150 mg tacrine hydrochloride per day. RESULTS: Serum concentration of tacrine hydrochloride and ratio of tacrine hydrochloride to metabolite were significantly higher in the 45 patients with symptomatic adverse effects (p < 0.001). The tacrine hydrochloride to metabolite ratio was significantly higher (p < 0.05) in the 30 patients in whom abnormal liver function developed, but concentration of tacrine hydrochloride was not significantly higher. Women showed a higher incidence of adverse effects (p < 0.05), and tacrine hydrochloride concentrations were higher (p < 0.05). Tacrine hydrochloride concentration and tacrine hydrochloride to metabolite ratio were higher in both men and women in whom adverse effects developed. CONCLUSION: Tacrine hydrochloride concentration is valuable in predicting the development of adverse effects, and its measurement may improve the use of the drug. PMID- 8513660 TI - A randomized controlled trial of computerized pharmacokinetic theophylline dosing versus empiric physician dosing. AB - This study was undertaken to determine if a computerized pharmacokinetic program for adjusting theophylline infusion rates could attain a goal serum theophylline level more accurately than physician-derived adjustments and what clinical impact this would have. Thirty-five patients with diagnoses of asthma or chronic obstructive pulmonary disease were randomized to a control group (empiric) or experimental group (kinetic) after initial theophylline levels were drawn from each group. After second levels were drawn, patients in the kinetic group had their infusion rates adjusted by the computerized pharmacokinetic program to achieve a level of 15 mg/L, whereas patients in the empiric group had their infusions adjusted empirically by the primary care physicians to achieve a serum theophylline level of 15 mg/L. A final theophylline level was obtained just before the infusion was discontinued. The kinetic group was closer to the goal level of 15 mg/L than the empiric group, but this was not statistically significant (14.8 +/- 4.4 versus 12.6 +/- 4.1; p > 0.05). The total number of days that patients were receiving intravenous theophylline was slightly longer for the kinetic group (4.1 +/- 3.3 versus 3.2 +/- 1.5; p > 0.05) as was the total number of hospital days, but neither of these were statistically significant (11.4 +/- 21.6 versus 8.8 +/- 15.4 days; p > 0.05). There were no differences between the two groups in the number of subtherapeutic or toxic levels, and there were no significant differences in arterial blood gas measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513662 TI - Constrained Markov networks for automated analysis of G-banded chromosomes. AB - Automated analysis of chromosome band patterns using probabilistic Markov networks has been reported in previous work. Band patterns are represented as strings of symbols. Inferred from a set of learning strings, a Markov network is a model of intraband and interband relations in these strings. The inference is entirely data-driven and is accomplished using dynamic programming. This paper presents a new model of chromosome band patterns, the constrained Markov network, which is a special case of its predecessor. Substantial experimental evidence of the superiority of the new model over the old is given in terms of equal results in centromere finding and improved results in classification for the 22 autosomes. Furthermore, a method for simplification of constrained Markov networks is shown to be of considerable importance with respect to computational complexity. PMID- 8513663 TI - Band features as classification measures for G-banded chromosome analysis. AB - Modern automatic and semiautomatic karyotyping systems employ algorithms that use chromosome length and centromeric index as well as other intact chromosome measures. These measures offer correct classification rates near 95%. An algorithm is presented that utilizes local dark band features and position (position from one end of the chromosome, band-width, band-height above light band background, integrated optical density above light band background, and a shape feature) and is based on maximum likelihood of the multivariate normal distribution for the feature vector. The algorithm was tested on two data sets: 179 metaphases from C. Lundsteen at the Rigshospitalet, Copenhagen, and 50 metaphases from The University of Texas M. D. Anderson Cancer Center. The Copenhagen set achieved an overall correct classification rate of 94.6% when classifying itself, a rate comparable to other algorithms. This classifier relies on local band features rather than global chromosome characteristics and is therefore directly extensible to metaphase and prophase chromosome subsegments and to structural abnormalities. PMID- 8513664 TI - Expanding the capabilities of laboratory instruments using built-in microprocessors and serial interfaces: adapting an LKB Ultrospec II UV spectrophotometer for scanning and enzyme kinetic analyses. AB - An IBM-compatible microcomputer was used to enable an LKB Ultrospec II UV-Visible spectrophotometer to perform two features which are not available on the basic unit: wavelength scanning and enzyme kinetic analyses. The spectrophotometer was controlled using a simple BASIC program, an RS232c interface and the instrument's own built-in microprocessor. This technique required no special analogue to digital conversion hardware or software and only a rudimentary knowledge of programming. User-designed software permits a greater degree of flexibility in routines and output formats than is offered in most pre-programmed instruments, while offering substantial savings. PMID- 8513665 TI - Automatic data acquisition of anthropological measurements. AB - A computer program in BASIC is presented which enables the input of measurement data from a caliper directly into specific records in a dBASE IV or PARADOX database. The program circumvents the tedious procedure of first recording measurement data manually and then entering the data into a computer. Thus much time can be saved and the risk of wrong data entry is lowered. The program was easy to use, and no significant problems were encountered. Necessary hardware is a standard IBM compatible desktop computer, Mitotoyu Digimatic (TM) calipers and a Mitotoyu Digimatic MUX-10 Multiplexer (TM). PMID- 8513666 TI - Longer-term growth prediction using GAUSS. AB - In several areas of biomedicine, one needs to predict future measurements for a growing individual on the basis of longitudinal data. Here we consider the problem of estimating the values of a given measurement for a particular individual at T-T* points in time, given T* observations on that individual, and all T values for a sample of N "similar" individuals. This extends our previous discussion [Schneiderman et al., Comput. Biol. Med. 22, 181-188 (1992)], which was limited to the case T* = T-1, to longer-term predictions. We again make a user-friendly GAUSS program available to perform the associated computations. Examples illustrating the use of the program and the accuracy of the predictions it provides are included. PMID- 8513667 TI - A FORTRAN program for the statistical analysis of incomplete time series data sets by a method of partition. AB - A program written in FORTRAN-77 which executes an analysis for periodicity of a time series data set is presented. Time series analysis now has applicability and use in a wide range of biomedical studies. The analytical method termed here a method of partition is derived from periodogram analysis, but uses the principle of analysis of variance (ANOVA). It is effective when used on incomplete data sets. An example in which a data set is made progressively more incomplete by the random removal of values demonstrates this, and a listing of the program and a sample output in both an abbreviated and a full version are given. PMID- 8513668 TI - Randomization algorithms in BASIC for experimental design. AB - Six BASIC programs for randomization of treatments with respect to space and time are presented. Program 1 is used to obtain randomization of several treatments in an equal number of positions for any number of replicates such that identical treatments are not replicated successively in the same position. Program 2 randomly assigns different treatments as specified in a grid of any size either (a) without constraints or (b) so that similar treatments do not occur next to each other either horizontally or vertically, or (c) horizontally, vertically, or diagonally. Program 3 assigns from five to 100 different treatments in equal proportions to a grid of specified size with treatments separated as in Program 2 (c) above. Program 4 randomly assigns any number of different treatments in equal proportions to a Latin square-like grid containing row and column cells with a multiple number of the treatments such that no identical treatments are replicated successively in the same row, column, or both row and column. Program 5 produces Latin squares of letters with unique numbered subscripts randomized. Program 6 makes Greco-Latin squares with an odd number of letters per side. These programs will aid in randomization of treatments within positions and replicates when a degree of uniformity or spacing of treatments is desired in order to increase the power of statistical tests. Examples of program output are discussed for tests with bark beetle pheromone components. PMID- 8513669 TI - Computer-assisted modeling of blood-flow: theoretical evidence for the existence of optimal flow wave patterns. AB - The purpose of this study was to model blood-flow waveforms in order to examine the relationship between various waveform shapes and input impedance spectra. Twenty distinct single cardiac cycle flow waveforms having the same mean flow and heart rate were created based on clinical and published observations. The "best" waveform was one with a steep flow upstroke, a high peak flow value, swift deceleration following peak flow, and flow reversal during diastole. Each flow waveform was paired with 20 computer-generated pressure waveforms to calculate input impedance spectra by discrete Fourier transformation. "Favorable" flow waveforms were associated consistently with a lower characteristic impedance (average of 4th-10th harmonics, Zav) irrespective of the shape or magnitude of the input pressure wave. Zav corresponds to the degree of compliance of the vascular bed and could be expected to be lower under favorable outflow conditions and in non-diseased vessels. In conclusion, this study provides theoretical evidence for the existence of optimal flow wave patterns and supports the notion of flow waveform assessment for diagnostic purposes. PMID- 8513670 TI - An algorithm for measurement of expiratory flow rate parameters on the partial expiratory flow-volume curve. AB - Partial expiratory flow-volume (PEFV) curves are a useful tool in airway challenge studies, but unlike the maximal expiratory flow-volume (MEFV) curve, lung function parameters require manual calculation from the flow-volume tracing. We describe an algorithm written in QuickBASIC that analyzes a PEFV curve superimposed on a MEFV curve by (1) identifying the PEFV curve, (2) locating the maximal expiratory flow at the point on the PEFV curve that corresponds to 60% of the baseline forced vital capacity (FVC) below total lung capacity (TLC), termed MEF40%(P), and (3) identifying the size of the PEFV curve along the TLC axis. A report of these parameters is also provided. This algorithm was validated using flow-volume curves from a clinical study in which eight subjects performed two sets of MEFV and PEFV curves separated by approximately 1 hr. Paired comparison of MEF40%(P) determined by the algorithm and two independent manual calculations correlated strongly and yielded no statistically significant differences between the two methods. We conclude that this algorithm provides rapid and accurate determinations of PEFV parameters. PMID- 8513672 TI - Menstrual blood loss with use of a vaginal ring releasing 20 micrograms levonorgestrel per day. World Health Organization. Task force on long-acting systemic agents for fertility regulation. AB - Menstrual blood loss (MBL), haemoglobin and serum ferritin levels were studied in a total of 127 women from three developing country centres, using a vaginal ring releasing 20 micrograms levonorgestrel/day. The objective was to evaluate changes in MBL and body iron stores over one year of use. The discontinuation rate for bleeding problems varied between centres from 3 to 13% at one year, but these differences were not significant. There were no differences in MBL or iron status on admission between women who completed or discontinued from the study. Even though there was considerable variation in MBL and haemoglobin levels among the three centres before insertion of the ring, a decrease in MBL was observed in all centres after commencement of ring use. Conversely, an increase in haemoglobin levels was noted in all centres although the change reached significance only in Beijing. There were no alterations in serum ferritin levels. These results suggest that use of a vaginal ring releasing 20 micrograms levonorgestrel/day for one year will not significantly affect menstrual blood loss volume nor cause changes in body iron stores. PMID- 8513671 TI - Fasting plasma lipids, lipoproteins and apolipoproteins in Nigerian women using combined oral and progestin-only injectable contraceptives. AB - Fasting plasma lipid, lipoprotein, and apolipoprotein (apo) profiles were determined in Nigerian women using a low-dose combined oral (Lo-Feminal + Fe) (n = 18), a progestin-only injectable (Depo-Provera) (n = 16) contraceptives and matched controls (n = 18). The mean of plasma total and low-density lipoprotein (LDL) cholesterol, apo B and Lp(a) were significantly higher (p < 0.01) in women using contraceptives than the controls. The mean of total and LDL-cholesterol and apo B were also significantly higher in the oral contraceptive users than those on progestin-only injectables. Furthermore, the mean of cardiovascular disease (CVD) risk indices, total/HDL-cholesterol (p < 0.05) and LDL/HDL-cholesterol (p < 0.01), were significantly higher in women on oral contraceptives than the controls. There were no statistically significant differences between the indices in the women using progestin-only injectables and the controls. Based on this finding, it is concluded that the use of steroidal contraceptives is associated with alterations of lipid and apolipoprotein profiles in Nigerian women and that the use of low-dose combined oral contraceptives may be associated with an increased CVD risk. PMID- 8513673 TI - Endometrial suction in luteal phase as a method of late postcoital contraception. AB - In a pilot study group of 25 women presenting in our clinic after exposure at ovulation to undesired pregnancy, endometrial suction by means of a Pipelle catheter was performed. Sixteen of the 25 women had proven fertility and 9 had never tried to conceive. The women were aged 18 to 38 years. Pathological dating of endometrial sampling verified that the patients were actually post-ovulation in all cases studied. hCG tests were performed 10 to 14 days after endometrial suction and all were negative. We conclude that endometrial suction in the luteal phase is a possible means of postcoital non-hormonal contraception, and we are currently expanding our study. PMID- 8513674 TI - Midtrimester induction of abortion: comparison of extraovular prostaglandin E2 and intra-amniotic prostaglandin F2 alpha. AB - The efficacy of extraovular prostaglandin E2 and intra-amniotic prostaglandin F2 alpha for pregnancy termination in midtrimester was compared. A retrospective review of pregnancy termination in midtrimester using intra-amniotic instillation of 40 mg of prostaglandin F2 alpha (n = 133) or extraovular instillation of prostaglandin E2 at a rate of 500 micrograms/hour (n = 81) was performed. Both groups had a similar mean induction-to-abortion interval (19.5 +/- 19.9 and 20.9 +/- 18.2 hours for extraovular PGE2 and intra-amniotic PGF2 alpha, respectively) and a similar success rate of abortion within the first 24 hours of initial treatment (84.0% for extraovular PGE2 and 76.7% for intra-amniotic PGF2 alpha). The two groups had a similar and low (9.8%) incidence of complications. It is concluded that either of the methods used in the study (i.e. extraovular PGE2 or intra-amniotic PGF2 alpha) can be used safely and effectively for pregnancy termination in midtrimester. PMID- 8513675 TI - Serum and endometrial copper, zinc, iron and cobalt with inert and copper containing IUCDs. AB - Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were measured in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippes loops users, 30 CuT-200 IUCD users and 24 matched controls by atomic absorption spectrophotometry. In the control group, there was no statistically significant difference in mean mid-luteal, compared to mid-follicular, levels of serum Cu, Zn, Fe and Co and endometrial Zn. Mid-luteal endometrium contained significantly higher mean Cu, and lower mean Fe levels. In Lippes loop users, compared to controls, the only statistically significant differences were lower mean mid-follicular serum Zn, lower mean endometrial Zn and Fe, and higher mean mid-luteal endometrial Fe. In CuT-200 users, compared to controls, there was significantly higher mean mid-follicular serum Zn and lower mean mid-luteal serum Co, higher mean mid-follicular endometrial Cu and lower mean mid-follicular endometrial Fe levels. Compared to Lippes loop, CuT-200 users had significantly higher mean mid-follicular serum Co and endometrial Cu and Zn, and lower mean mid follicular endometrial Fe. PMID- 8513676 TI - Antifertility effects in female rats immunized with human seminal plasma inhibin. AB - Adult female rats were actively immunized with sperm-coating protein (10.4 KDa) human seminal plasma inhibin (HSPI). Following 8 weeks of immunization at 2.5 micrograms and 5 micrograms doses of HSPI with Freund's complete adjuvant, antifertility effects were observed in 63% (5/8) and 88% (7/8) of animals, respectively. Estrous cycle was not affected in experimental group. Thus, the present study suggests the potential use of HSPI for immunocontraception in females. PMID- 8513677 TI - Potentiating effect of epostane on pregnancy terminating activity of RU 486 in the rat. AB - The effectiveness of a combination of RU 486, an antiprogestin, and epostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, for termination of pregnancy in female rats was determined. Epostane administered at doses ranging from 8 to 48 mg/Kg/day on days 7, 8, and 9 of pregnancy did not influence the progress of the pregnancy. RU 486 in doses of 1, 2, and 4 mg/Kg/day terminated pregnancy in 0, 40, and 100% of rats, respectively. The combination of epostane (48 mg/Kg/day) plus RU 486 (1 and 2 mg/Kg/day) terminated pregnancy with complete resorption of fetuses in all treated animals. Unexpectedly, the drug combination that terminated pregnancy used a dose of epostane that was not highly effective in lowering serum progesterone levels when epostane was administered alone. Thus, in the rat, the synergistic action of epostane plus RU 486 may not be dependent upon reduced progesterone secretion plus receptor blockage as anticipated. The present results suggest that the combination of epostane plus RU 486 is effective for pregnancy termination. PMID- 8513678 TI - Developing a radioimmunoassay for anordrin: the synthesis of propionyl and hemisuccinyl esters of anordiol. AB - We describe the chemical synthesis of the 2 beta-propionate-17 beta- hemisuccinate and 2 beta-hemisuccinate-17 beta-propionate diesters of anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) and the method for coupling them to bovine serum albumin and Affi-gel 102, in order to prepare antibodies for radioimmunoassay of anordrin. In addition, we describe the chemical synthesis of the following derivatives: 2 beta-ol-17 beta-propionate, 2 beta-propionate-17 beta-ol, 2 beta-hemisuccinate-17 beta-ol, and 2 beta-ol-17 beta-hemisuccinate. PMID- 8513679 TI - Recent advances in surgery for colon and rectal cancer. AB - Surgery is the mainstay of therapy for colon and rectal cancer. Over the past several decades, there have been important advances both in the understanding of the biology of colon and rectal cancer and in the preoperative and operative techniques for treating this disease. Although it appears in some studies that we have made a difference in the survival rates in the treatment of colon and rectal cancer, in actual fact, this phenomenon may only be secondary to better staging and, therefore, a greater ability to prognosticate a particular patient's chance of cure. What has been learned in the past 20 to 30 years is that most colon and rectal carcinomas start as polyps of the colon and rectum. Most often, polyps are sporadic, but there are certain high-risk groups that produce polyps and, consequently, colon and rectal cancer at a much higher rate. The goal of a practicing physician is to identify these high-risk individuals and to recommend frequent screenings so as to intervene before a polyp has had a chance to become a deeply invasive cancer. These high-risk groups are best typified by familial adenomatous polyposis, which if left untreated will, in 100% of cases, lead to the death of a patient from colon or rectal cancer. Other diseases that lead to an increase in colon and rectal cancer but may not go through the usual adenoma to-carcinoma sequence include inflammatory bowel disease such as Crohn's colitis and ulcerative colitis. Most patients with colorectal carcinoma are asymptomatic at the time of diagnosis. This phenomenon has led to efforts to screen the general population for polyps and for cancer. Screening techniques such as the detection of occult blood in the stool and endoscopic procedures are currently the most popular. It is unclear at this time exactly what the efficacy of these techniques is in improving the survival of the general population from colorectal carcinoma. The surgical techniques to remove colon and rectal carcinomas have recently expanded to include a more aggressive local excision policy for small tumors of the rectum and the application of laparoscopic techniques, new stapling techniques, and new anastomosing techniques for tumors of the colon and rectum. These techniques have become possible in part through advances in surgical instrumentation and also in part from our increasing understanding of the biology of the disease. Both have allowed for more creative approaches to diagnosing and treating colon and rectal cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513680 TI - Late effects of childhood cancer therapy. PMID- 8513682 TI - Allergic contact dermatitis (caused by rubber cosmetic sponges) simulating cosmetic dermatitis. PMID- 8513681 TI - Pediatric endocrinology. PMID- 8513683 TI - Psoriasis: a stress-related disease. AB - Stress is a well-known triggering factor in the appearance or exacerbation of psoriasis. The concept of psychoneuroimmunology in relation to stress is described. As part of the total care of the psoriasis patient, physicians are urged to augment traditional psoriasis treatment regimens with stress-reduction strategies, such as biofeedback, meditation, and self-help approaches. PMID- 8513684 TI - A dermatologic diary. Portrait of a practice. PMID- 8513685 TI - Hair in infancy and childhood. AB - Of concern to new mothers is often the question, "Does my baby look normal?" In regard to the scalp and hair patterns of the infant, we have provided at least a basic guideline of what is generally considered the norm or variants of normal. Our goal was to outline accepted methods to care for an infant's hair and present certain problems a mother could encounter concerning the hair and scalp of her child or adolescent. We wish for this to serve as a practical guide to physicians in preparing mothers to care for their child's hair needs. PMID- 8513686 TI - Snapshots versus medical photographs: understanding the difference is your key to better dermatologic office photography. AB - A medical photograph in contradistinction to a snapshot accurately reproduces and maximizes clinically significant information while minimizing extraneous or irrelevant factors. Obtaining a top-notch medical photograph requires not only proper equipment but also rapid, sophisticated analysis of the clinical situation. Only then can major features including lesional size and distribution and more subtle details such as borders, color, and topography be selectively highlighted. First-rate medical photographs not only enhance the accuracy of diagnosis but also facilitate subsequent assessment of therapeutic efficacy. Furthermore, instruction of students and residents and continuing medical education of practicing clinicians depend on our photographic acumen. PMID- 8513687 TI - Blistering distal dactylitis caused by Staphylococcus aureus. AB - Blistering distal dactylitis is a superficial infection of the anterior fat pad on the volar surface of the distal portion of ordinarily a single finger. Although most commonly caused by group A beta-hemolytic streptococci, we report a case of blistering distal dactylitis caused by Staphylococcus aureus involving all the fingers and thumbs of a child. After results of a Gram's stain and culture established the diagnosis, the child responded rapidly to oral amoxicillin trihydrate/clavulanate potassium (Augmentin). Multiple fingers affected in blistering distal dactylitis may be a predictor of S. aureus as the causative agent. PMID- 8513689 TI - Unusual features of pyoderma gangrenosum: two atypical cases. AB - Two cases of pyoderma gangrenosum are described that are atypical in the appearance of their skin lesions and their association with intestinal diseases. PMID- 8513688 TI - Lennert's lymphoma presenting as prurigo nodularis. AB - Lennert's lymphoma is a peripheral T-cell lymphoma that only rarely involves the skin. We present the case of a forty-two-year-old man who experienced severe pruritus for ten months. He was repeatedly diagnosed as having neurodermatitis and prurigo nodularis before subtle hematologic clues suggested, and subsequent examination of bone and lymph node biopsy specimens confirmed, the diagnosis of Lennert's lymphoma. This report describes the case and presents a brief review of Lennert's lymphoma. PMID- 8513690 TI - Verruciform xanthoma of the glans penis: a benign clinical simulant of genital malignancy. AB - Verruciform xanthoma is a benign disorder affecting skin and mucosa. Although most cases have been reported to occur in the mouth, other sites may be affected, most notably the genitalia. A large, exophytic verruciform xanthoma involving the glans penis is reported. The clinical similarity to a malignancy, especially verrucous carcinoma, is emphasized. The differential diagnosis and histologic features are reviewed along with a summary of the literature regarding this uncommon condition. PMID- 8513691 TI - Fluoxetine is an effective treatment for neurotic excoriations: case report. AB - A fifteen-year-old girl with a two-year history of severe neurotic excoriations and an obsessive-compulsive disorder experienced a dramatic improvement of her neurotic excoriations after a six-week course of fluoxetine 20 mg per day. This is in contrast to most previously reported treatments, which typically were only moderately effective. The neurobiological basis for the efficacy of fluoxetine, an antidepressant that is a potent serotonin reuptake inhibitor, in the treatment of neurotic excoriations associated with an obsessive-compulsive disorder, is reviewed. PMID- 8513692 TI - Detection of in situ hybridization to human chromosomes with the atomic force microscope. AB - Atomic force microscopy (AFM) permits one to generate a topographic representation of the sample under investigation with high spatial resolution. We assumed that cytochemical staining techniques, which yield reaction products which can be discriminated from the surrounding material on basis of their topographic properties, would be applicable in AFM. Here we show the validity of this assumption by employing an in situ hybridization technique in which the final label was the precipitated product of a peroxidase/diaminebenzidine reaction. After hybridization of the DNA probe pUC1.77 that recognizes the heterochromatic region of human chromosome 1 (1q12), the AFM clearly detects the sites of in situ hybridization. In situ hybridization with DNA probe p1-79 results in clear marking of the telomere region 1p36. The diameter of the probe p1-79 linked reaction product was 75-100 nm, indicating that resolution of 200 nm can readily be reached with this AFM approach of DNA mapping. This precision is directly linked with the amount of precipitated material. PMID- 8513693 TI - DNA content measurements and an improved idiogram for the Indian muntjac. AB - The Indian muntjac, an asiatic deer, has the lowest diploid chromosome number among mammals (female 2N = 6; male 2N = 7). Using flow cytometric quantification of propidium iodide-stained cells, we determined the DNA content of muntjac cells to be 94% that of human. This suggests that the muntjac may serve as a model for investigation of karyotypic evolution and rearrangement. In order to facilitate future comparative gene mapping studies, computer-aided analysis of digitized metaphase chromosomes allowed development of a detailed Indian muntjac G-banded idiogram incorporating both ISCN-type nomenclature and quantitative estimates of the size of each band and position. PMID- 8513694 TI - DNA content in Eurasian sturgeon species determined by flow cytometry. AB - The nuclear DNA content in 10 species of chondrostean fishes was measured by flow cytometry. The sterlet Acipenser ruthenus blood cells were used as an internal standard. The sterlet DNA content was calculated on the basis of comparison with the Xenopus laevis blood cells, 2C = 6.30 pg. In the tetraploid A. ruthenus and A. stellatus the DNA content comprises 3.74 pg/nucleus and is practically invariant; in Huso dauricus it is almost the same, 3.74-3.81 pg; and in A. nudiventris it is a little higher, 3.88-4.04 pg. In the oldest chondrostean, Pseudoscaphirhynchus kaufmanni, the nuclear DNA content is slightly lower, 2C = 3.46-3.48 pg, and in the American paddlefish Polyodon spathula it is lower still, 3.17 pg. In two octoploid sturgeons, A. baeri and A. gueldenstaedti, the DNA content is twice as high as that of the sterlet, 8.29-8.31 and 7.86-7.88 pg, respectively; a very similar amount, 8.24-8.42 pg, was determined in the hybrid Huso huso x A. ruthenus. In the Sakhalin sturgeon, A. medirostris (= A. mikadoi), the DNA content is two times higher than in the octoploids, 13.93-14.73 pg; therefore its ploidy may be 16n and the number of chromosomes could be 500. PMID- 8513695 TI - Kinetic analysis of cytotoxic lymphocyte-target cell interaction as quantified by dual parameter flow cytometry. AB - The kinetics of conjugate formation between leukemic cell lines (K562 and Daudi) and lymphokine-activated killer (LAK) cells was studied. A flow cytofluorometry method using double immunofluorescence staining was applied. During the first 15 min of incubation of LAK effectors with leukemic targets, a rapid binding occurred, followed by a plateau phase lasting until 30 min of observation. A considerable, yet not statistically significant, between-donor variability was noticed. A mathematical model of conjugate formation kinetics, based on the analogy to enzyme kinetics, was formulated and validated. Parameters of the model were related to the binding capacity of effector and target cells, and to the lifetime of conjugates and free cells. The concordance of theoretical curves with experimental data proved that the described model can be considered as a useful tool for the evaluation of kinetic and dynamic characterization of conjugate formation between leukemic targets and LAK effectors. PMID- 8513696 TI - Forward scatter pulse width signals resolve multiple populations of endosomes. AB - The technique of pulse width analysis, developed to optimize cell size resolution in cell cycle kinetics, has not previously been applied to small particles such as endosomes. Offset is used to subtract a portion of the beam diameter from forward scatter pulse width signals to optimize visualization and discrimination of small particles. We identify multiple endosomal populations by offset pulse width of light scatter parameters. Specifically, linear forward scatter pulse width measurements reveal at least two populations of endosomes in the rat renal cortex, the rat renal papilla, and the luminal endothelium of the toad urinary bladder. Logarithmically amplified forward scatter pulse width measurements display the full dynamic range of these signals, resolving additional populations not manifest with linear amplification. To confirm that the endosomes observed were resolved from optical and electronic noise, we examined physiological function. The endosomes acidified after supplying ATP to the intrinsic membrane H(+)-ATPase present. Further, electron microscopy of sorted endosomal populations from the toad urinary bladder confirmed identity and homogeneity of the fraction. Flow cytometric analysis of endosomal populations by multiparametric techniques including pulse width analysis of structural parameters and pulse height analysis of fluorescence from entrapped fluorophores allows identification, isolation, and quantification of multiple endosomal populations. PMID- 8513697 TI - Whole blood method for simultaneous detection of surface and cytoplasmic antigens by flow cytometry. AB - Dual parameter analysis of surface antigens in flow cytometry has become a standard method for detection of cell subsets. However, few methods have been described for the extension of multiparameter analyses to include cytoplasmic or intracellular antigens. Here we describe a simple and reproducible method for simultaneous detection of surface and intracellular antigens by flow cytometry in lysed whole blood samples. This method employs the use of digitonin, a mild glycoside detergent, and formaldehyde for permeabilization and fixation. Red blood cells are lysed with 2% acetic acid. Preparation of samples in this manner resulted in altered light scatter characteristics relative to unpermeabilized samples; however, gating issues were overcome using a combination of scatter vs. fluorescence gating. Quantitation of CD3+/CD4+ and CD3+/CD8+ cells using this method was equivalent to counts obtained with the reference method using a commercially available lysis procedure and fluorescence vs. scatter gating. The effectiveness of the permeabilization process was assessed using a monoclonal antibody designated TIA-1, which is specific for a cytoplasmic antigen associated with cytotoxic granules predominantly found in CD8+ cells. The method effectively quantitated TIA-1 positive cells and demonstrated the specificity of the reagent for a subpopulation of CD8+ lymphocytes. Using this simplified procedure for simultaneous identification of surface and cytoplasmic antigens could help in studies of cell activation, proliferation, and other functional characteristics of the immune system. PMID- 8513698 TI - Demonstration of an S phase population of cells without DNA synthesis generated by cisplatin and pentoxifylline. AB - Dual parameter flow cytometry measuring DNA and BrdUrd uptake in "stripped" nuclei was used as a sample preparation procedure. The utility of this method is demonstrated in a human ovarian cell line (BG-1) by two parameter flow cytometric analysis of DNA and bromodeoxyuridine (BrdUrd) incorporated into the DNA. BG-1 cells, treated with cisplatin followed by constant exposure to pentoxifylline, produce G0/G1, S phase, and G2/M perturbations. The G0/G1 population is greatly diminished. Large numbers of cells are distributed in S phase in which a large portion is incapable of DNA synthesis. The G2/M perturbations show a continually increasing block over a time course of 168 h. The identification of two types of S phase cells (DNA synthesizing and DNA nonsynthesizing) is clearly shown with the use of BrdUrd incorporation as a second parameter in addition to flow cytometric analysis of DNA. This increase in the non-DNA-synthesizing S phase population corresponds to an enhancement of cytotoxicity when cells are treated with the combination of cisplatin and pentoxifylline. It is felt that this technique provides a useful method to investigate the dynamics of the cell cycle perturbations affected by modulators of chemotherapeutic agents. PMID- 8513699 TI - Two-color flow cytometric analysis of intraerythrocytic malaria parasite DNA and surface membrane-associated antigen in erythrocytes infected with Plasmodium falciparum. AB - A method for fixation of Plasmodium falciparum infected erythrocytes and solubilization of the erythrocyte membrane with detergent was developed. This method was applied to two-color flow cytometric analysis of both intraerythrocytic (IE) malaria DNA and parasite-derived antigen on the erythrocyte surface membrane. Infected erythrocytes were fixed with 0.025% glutaraldehyde followed by treatment with 1% saponin to gain access to intramembranous components and allow antibody to interact with antigen. DNA of IE parasite was subsequently stained with propidium iodide. Using this procedure cell morphology was well preserved with excellent parasite DNA staining. Using anti-malaria antibodies which recognize ring-infected erythrocyte surface antigen (Pf155/RESA), we observed that glutaraldehyde-fixed saponin treated infected erythrocytes exhibited a variable immunofluorescence intensity as assessed by both flow cytometry and fluorescence microscopy. Ring-infected cells displayed strong immunofluorescence staining, whereas a weak signal was detected on cells containing schizonts. Simultaneous measurement of parasite DNA and antigen in the infected erythrocyte membrane can facilitate the study of antigen expression in the cell membrane in association with development of IE parasites. PMID- 8513700 TI - Signal processing in slit-scan flow cytometry of cell conjugates. AB - The design and implementation of a real-time signal processing system for slit scan flow cytometry is described. The system is used to measure the separate scatter and fluorescence peak heights of 2 adherent cells. Preliminary measurements of changes in the membrane potential induced by interactions between natural killer (NK) cells and their target cells are presented. PMID- 8513702 TI - The future of cytology in independent laboratories. PMID- 8513701 TI - Separation of rooster spermatogenic nuclei by means of centrifugal elutriation. AB - By application of minor variations in the usual method of centrifugal elutriation, we have been able to separate a nuclear suspension from rooster testes. We have obtained a population of elongated or late spermatid nuclei (98% purity), a population of round or early spermatid nuclei (90% purity), and, finally, a mixed population of meiotic and pre-meiotic nuclei. PMID- 8513703 TI - The future of cytology: prospects for the nonprofit hospital cytology laboratory. PMID- 8513704 TI - The future of cytopathology in the academic medical center. PMID- 8513705 TI - Thyroid tumors: cytomorphology of Hurthle cell tumors, including an uncommon papillary variant. AB - Of 2,012 fine-needle aspirations (FNA) performed by us between 1984 and 1988, we present a detailed cytomorphologic analysis of 95 cases that were diagnosed as neoplastic on histology and/or cytology and those that received an equivocal cytodiagnosis. Discussed are eight tumors, which include three classic and five variant forms of Hurthle cell carcinoma. The latter showed a papillary tumor populated wholly by Hurthle cells, which we have morphologically designated as papillary Hurthle cell carcinoma. All three Hurthle cell carcinomas (PHC) were diagnosed on FNA as papillary Hurthle cell neoplasms (PHN). One was a false negative cytodiagnosis. PMID- 8513707 TI - Fine-needle aspiration biopsy: dermatofibrosarcoma protuberans. AB - Dermatofibrosarcoma protuberans (DFSP) represents a spectrum of mesenchymal spindle cell tumors that typically involve both dermis and subcutis. Presented herein are six cases of DFSP, four of which were initially diagnosed by FNAB. The cytologic features useful in the identification of this lesion on Papanicolaou- and Diff-Quik-stained smears are discussed. Chief among these are the storiform stromal fragments, presence of entrapped adipose tissue and the recognition of fibrohistiocytic spindle cells. The potential pitfalls and the differential diagnostic possibilities of spindle-cell lesions, particularly those of fibrohistiocytic origin are discussed. PMID- 8513706 TI - Quality-assurance study of simultaneously sampled, non-correlating cervical cytology and biopsies. AB - As part of a quality assurance study, we reviewed 223 cases of simultaneously sampled cervical smears and biopsies that showed a significant lack of correlation for squamous dysplasia or carcinoma. In 153 of the 223 cases (68.6%), the cytology was negative and the biopsy positive. After review of the specimens, errors in this group were found to be of the following types: sampling 64%, interpretive 29%, and combined sampling and interpretive 7%. In the remaining 70 cases (31.4%), the biopsy was negative and the Papanicolaou smear positive. In these cases, the following types of errors occurred: sampling 54%, interpretive 33%, and combination 13%. Twenty-nine of these 70 patients showed dysplasia on follow-up material. These findings indicate there are a significant number of false-negative Papanicolaou smears, mostly because of sampling problems. There are few false-positives. In cases of positive Papanicolaou and negative biopsy, dysplasia is likely to be present in subsequent samples. PMID- 8513708 TI - Sialadenosis of the parotid gland: report of four cases diagnosed by fine-needle aspiration cytology. AB - Four patients presented with a history of recurrent bilateral swellings of parotid glands. Fine-needle aspiration (FNA) specimens showed highly cellular smears containing clusters of enlarged acini and numerous naked nuclei. A diagnosis consistent with sialadenosis was made considering the distinct morphologic appearance: micrometric measurements in all cases, in addition to histology and electron microscopy in two cases confirmed this hypothesis. A review of clinical histories revealed hormonal, nutritional and neurogenic disorders, which are known to be associated with sialadenosis. In the work-up of salivary gland swellings, it is important to recognize cytologically this underestimated entity, which does not necessarily require surgical treatment. PMID- 8513709 TI - Fine-needle aspiration cytodiagnosis of breast masses in pregnant and lactating women and its impact on management. AB - We reviewed our experience with 9,726 cases of fine-needle aspiration cytology of the breast that were done from January 1983 to February 1992. During our review, we found that 214 aspirates had been submitted from pregnant and lactating women for the investigation of breast mass(es). Despite a variable clinical presentation and spectrum of cytologic findings, we considered the application of aspiration cytology in these women as useful as in the nonpregnant-nonlactating women for management decision. A team approach between the clinician and cytopathologist was always maintained; with this approach, the false-positive or negative diagnoses were reduced to almost nil. In all cases in which the cytodiagnosis of carcinoma of breast was made, the findings corresponded with subsequent cell blocks from the aspirate and tissue examination. Benign lesions were diagnosed cytologically with minimal difficulty, and all aspirates that were less than optimal for cytodiagnosis were repeated to minimize the chance of missing an abnormality. All the benign lesions were followed throughout pregnancy, postpartum, and thereafter; if the mass persisted, the aspiration was repeated. With this protocol of follow-up, the need for a customary liberal surgical biopsy was reduced to a minimum. PMID- 8513710 TI - Prognostic value of breast cancer cytologic grading: a retrospective study of 213 cases. AB - The authors evaluate 213 consecutive breast cancer cases with positive fine needle aspiration cytology. Cytologic smears were reviewed and classified according to a grading system. A correlation between cytologic grading and pathological stage (T and N category) was observed. Univariate analysis of 5-yr overall survival rate showed a significant negative association with prognosis only for G3 (90%) compared to G1 (72%) cases. Such prognostic correlation was no longer significant at multivariate (Cox) analysis adjusting for potential confounders such as T or N categories. The prognostic value of cytologic grading is limited and dependent on other classic prognostic indicators that are currently determined in breast cancer patients. Its practical value is negligible, as it does not improve the prognostic judgment. PMID- 8513711 TI - Value of Papanicolaou smear in detection of Chlamydia trachomatis infection. AB - This study was undertaken to assess the value of Papanicolaou smear for the diagnosis of Chlamydia trachomatis infection. The study was both retrospective (groups I and II) and prospective (group III). Group I consisted of 41 smears with cytomorphological changes proposed by Gupta, Kiviat, or Shiina. Group II was a control group, consisting of 30 cytologically normal smears. All these smears were subjected to specific immunofluorescent (IF) staining under identical conditions to confirm the diagnosis. In group III, 40 consecutive duplicate cervical smears were collected from patients attending the Sexually Transmitted Disease Clinic. One smear was routinely examined, and the specific IF staining was done on the other smear. The results in all the three groups were analysed. It was concluded that Papanicolaou smear is not useful in the detection of Chlamydia trachomatis infection. PMID- 8513712 TI - Diagnostic accuracy and clinical utility of fine-needle aspiration cytology in the diagnosis of clinically primary bone lesions. AB - Optimal treatment of primary bone sarcomas requires minimal disturbance of the tumor prior to preoperative radiation and chemotherapy. Currently, carefully planned incisional or cutting needle biopsies are the favored methods for procurement of specimens. Recently, fine-needle aspiration has gained favor as the initial diagnostic procedure at some centers. We investigated the diagnostic accuracy and the effects of errors in diagnosis and of complications on the patient's course in a series of 101 patients presenting with lesions clinically believed to have arisen in bone. We found that 29% of aspirates were insufficient for the diagnosis; 41% of aspirates yielded a correct diagnosis that had a significant favorable impact on the patient's course, while 20% of aspirates gave a correct diagnosis that did not significantly influence therapy. In 7% of cases, the aspirates were associated with an incorrect diagnosis that negatively influenced therapy, and in an additional 3% of cases an incorrect diagnosis was obtained that had no impact on patient outcome. No complications were encountered in this series of patients. PMID- 8513713 TI - Transplant aspirative cytology: analysis of morphological and immunocytochemical parameters in renal allograft dysfunction. AB - We have analyzed 245 transplant aspirative cytologies (TACs) from 96 renal allograft patients. TACs were divided in two chronological groups: Early (TACs performed during the first 3-mo posttransplantation) and late (TACs performed after the third month post-transplantation), in order to assess the effect of allograft tolerance on TAC features. Both morphological and immunocytochemical aspects were evaluated, including CD4, CD8, IL2-R, and HLA-DR immunolabeling. A final diagnosis for each case of allograft dysfunction was achieved by other independent diagnostic means. Four diagnostic groups were considered in the present study: acute rejection (AR), chronic rejection (CR), acute tubular necrosis (ATN), and Cyclosporin A toxicity (CsA-T). In addition, a control group (C) was established from patients with stable allograft function. We found that immunocytochemical analysis of TACs is particularly helpful in the diagnosis of late allograft dysfunction, a time period when the simple cytological study of renal infiltrate is not informative enough to help take therapeutic decisions. PMID- 8513714 TI - Monoclonal antibody 44-3A6 as an adjunct in cytodiagnosis of adenocarcinomas in body fluids. AB - Monoclonal antibody (MCA) 44-3A6 detects a cell-surface transmembrane phosphoprotein frequently expressed by pulmonary adenocarcinoma (AC) and associated with glandular differentiation. This antibody has been found to have utility in assessing routine formalin fixed paraffin-embedded pulmonary neoplasms, as well as the cytopathological evaluation of sputum and bronchial brushings. Recently, it has been shown to be useful in cytological diagnosis of pleural effusions. This study is directed at evaluating its effectiveness in detecting immunoreactive neoplastic cells in body fluids (BF) arising in other tissues. A retrospective cohort of 57 cases was studied, consisting of 36 pleural, 19 ascitic, and 2 pericardial BF. After evaluation of Papanicolaou stained slides, the BF specimens were immunostained with MCA 44-3A6 using the avidin-biotin-peroxidase complex (ABC) method. In 29 cases, tissue sections of the primary tumors, were also available for immunostaining with MCA 44-3A6. Results showed that 39/42 (93%) of AC BF cases were positive and 28/42 (66%) stained intensely (3-4+) with 75-100% of the AC cells staining in each case. All of the 18 benign and non-AC malignant BF were negative. The staining patterns in the tissue sections of the 29 cases that had corresponding BF samples were similar. We conclude from this study that the MCA 44-3A6 (1) is useful in detecting cells consistent with AC in BF; (2) does not stain inflammatory cells or reactive mesothelial cells, thus helping distinguish reactive from malignant BF; and (3) frequency and pattern of expression in BF parallels its expression in tissue specimens. This study confirms that this MCA is a useful adjunct tool in the cytopathological evaluation of BF. PMID- 8513715 TI - Aspiration cytology of maxillary myxoma. AB - Fine-needle aspiration was used to diagnose a case of maxillary myxoma. Abundant mucoid material was obtained. Microscopic examination showed three-dimensional fibrillary myxoid fragments entangling spindle-shaped, stellate, and fusiform cells with round to oval monomorphic nuclei. A striking feature was delicately branching capillaries. The diagnosis was subsequently confirmed on histology and histochemistry. PMID- 8513716 TI - Fine-needle aspiration cytology of primary large-cell lymphoma of the mediastinum: cytomorphologic findings with potential pitfalls in diagnosis. AB - We report the fine-needle aspiration (FNA) cytomorphologic features of six cases of primary mediastinal large-cell lymphoma with sclerosis. The series consisted of three men and three women with a median age of 36 yr. All the patients presented with a large anterior or superior mediastinal mass with no evidence of peripheral lymphadenopathy or hepatosplenomegaly. Two of the cases showed typical findings of lymphoma, characterized by hypercellular specimens with numerous individually scattered markedly atypical lymphoid cells present, demonstrating nuclear irregularity with the presence of nucleoli and surrounding scant to slight amount of cytoplasm. Numerous lymphoglandular bodies were seen in the background. Both cases were correctly diagnosed as representing non-Hodgkin's large-cell lymphomas. Two other cases had slight cellularity with the presence of a few scattered atypical lymphoid cells. Although a definite diagnosis was not rendered in either case, the possibility of malignant lymphoma was considered. Two other cases consisted predominantly of microtissue fragments with some associated scattered individual atypical cells. Within the microtissue fragments, the cells were distorted with a tendency to elongate and spindle in a prominent fibrous matrix. Our experience demonstrates that FNA cytology of primary mediastinal diffuse large cell lymphoma with sclerosis can be challenging, with a potential for a false-negative diagnosis due to limited cellularity secondary to the sclerosis or a misdiagnosis as a spindle cell neoplasm due to distortion of these cells by the fibrous matrix. To the best of our knowledge, we believe this is the first FNA series of primary mediastinal diffuse large cell lymphoma with sclerosis. PMID- 8513717 TI - Salvaging the too thick fine-needle aspirate smear. PMID- 8513718 TI - Symptomatic treatment of nephrotic syndrome. PMID- 8513719 TI - A study of urinary tract infections at Ile-Ife, Nigeria. AB - Clinical laboratory records and case files of 1,038 cases of urinary tract infections (UTI) were examined for the spectrum of bacterial and candida isolates for age and sex distribution of the UTI cases and antibiotic susceptibility pattern of isolates. The results show that 867 (83.5%) of the cases were aged 21 years and above, of which 81.3% in that age group were females. While only 20.7% of the cases were males, 74.0% of those in that category were also 21 years and older. Eleven organisms were isolated, with E. coli, Klebsiella spp and Staphylococcus aureus respectively representing 36.1%, 22.8% and 15.4% of the total bacterial isolates. The prevalence of S. aureus isolates in cases of UTI in this centre suggests the increasing role of these microorganisms in the aetiology of urinary tract infections in Nigeria. PMID- 8513720 TI - Experience with the use of human albumin in renal patients at the Kenyatta National Hospital. AB - In a 20-month period (May 1990 to December 1991), 34 patients with diuretic resistant oedema due to nephrotic syndrome, 4 patients with severe hypotension during haemodialysis and 3 patients with refractory ascites on chronic haemodialysis were treated with infusion of highly purified human placental albumin (HPHPA). In the 34 patients with resistant oedema due to nephrotic syndrome, infusion with HPHPA resulted in prompt diuresis, weight loss and normalisation of the blood urea nitrogen. These effects were maintained for three weeks after stopping the daily infusions, but started reverting to the pretreatment levels thereafter. Twelve of the 34 patients in whom prior attempts or renal biopsy had failed because of gross oedema, had this done following the resolution of oedema. In the 4 patients with severe hypotension (blood pressure, Systolic/Diastolic mmHg; Mean SD +/- 792 +/- 50 +/- 9) during haemodialysis the blood pressure rose to 135 +/- 11/87 +/- 8 following a rapid infusion of 100mls of 25% HPHPA and remained at that level during the course of haemodialysis. Three patients on chronic haemodialysis with refractory ascites were treated with four sessions of large-volume paracentesis. At each session they were infused with 200mls of 25% HPHPA over one hour. No clinically overt haemodynamic disturbance was noted thereafter and the patients were relieved of abdominal discomfort and respiratory difficulties for a period varying between 4 and 11 weeks before the ascites reaccumulated. PMID- 8513721 TI - Prognostic factors in typhoid perforation. AB - A review of 60 patients undergoing surgery of typhoid perforation at the Ahmadu Bello University Teaching Hospital in Northern Nigeria between January 1981 and April 1987 was performed. Solitary perforation of the terminal ileum was found in 45 of 58 (78%) patients. 52 (87%) patients had debridement of the edge of perforation and simple closure. The overall hospital mortality was 57%. Important prognostic factors identified were blood urea level and duration of perforation before admission. In order to improve prognosis in typhoid perforation, patients must present early to hospital where early diagnosis, aggressive resuscitation and prompt surgery should be carried out. PMID- 8513722 TI - Factors related to upper gastrointestinal haemorrhage in Africans. AB - The aetiological factors in 84 patients with acute upper gastrointestinal tract(UGIT) haemorrhage were studied. Sixty of the patients (71.4%) were between their 3rd and 5th decades of life. Acute alcohol consumption and drugs are the commonest single or combined factors in 76 patients (90.5%). Twenty-four patients (28.6%) had previous episodes of UGIT haemorrhage. Antacids, (which are cheaper and preferred by most of the patients), are found to be as effective as H2 blockers. The need to educate the young adults on the dangers of alcohol, nicotine and indiscriminate use of drugs is stressed. PMID- 8513724 TI - Calculation of creatinine clearance from plasma creatinine. AB - Glomerular filtration rate (GFR) is commonly assessed by measurement of endogenous creatinine clearance (Ccr). Several formulae have been described to calculate Ccr from plasma creatinine. I have evaluated the effectiveness of four formulae in 35 healthy subjects (21M and 14F, 18-34 years) and in 41 patients (24M, 17F, 20-69 years) attending a renal clinic with diminished renal function (serum creatinine 200-600 mumol/l). The GFR was measured using 51 Cr-EDTA clearance and endogenous Ccr. The Ccr was also estimated by four formulae. In healthy subjects Ccr calculated by the formulae of Cockcroft and Gault and Hull et al gave higher correlation coefficient (0.710 and 0.714 respectively) with endogenous Ccr than the formulae of Gates and that of Jellife (0.514 and 0.586 respectively). When all the subjects with a wide range of GFR (3.5-145 mls/min) were considered all the four formulae gave reasonable correlation, but the formula of Cockcroft and Gault was the best. It is recommended that in developing counties with limited resources, the formula of Cockcroft and Gault can be used to estimate Ccr from plasma creatinines. PMID- 8513723 TI - Female involvement in intervention programmes: the EPI experience in Saradidi, Kenya. AB - The paper addressed itself to the issue of community participation in intervention programme and that if the beneficiaries are women, then the category of people to be involved in the programme should be women. In buttressing this, the nursing superintendent of an Expanded Programme on Immunization (EPI) programme in Saradidi, rural Kenya together with 184 mothers attending the clinic were interviewed. The majority (89%) were of the view that in Maternal and Child health (MCH) programmes, it is only ideal that women should be involved because this tend to blend with their traditional roles of child bearing and nurturing and moreover, in such matters, women would tend to relate better to other women rather than men; women would again tend to show greater willingness and commitment to help other women. This was even butressed by the fact that the majority of the mothers interviewed were prepared to participate in such programmes geared towards helping other women. The women explained that contrary to the belief that rural women are so preoccupied with survival that they hardly have time for relaxation, they do have the time to visit friends, especially in the evenings, participate in church activities and knit. A case was thus made for greater female involvement in intervention programmes where the target population is women. If maximum success is to be achieved, there is need for greater female involvement in intervention programmes geared towards improving the lot of women and children. PMID- 8513725 TI - A preliminary survey for intestinal parasites in the Tis Abay town, northwest Ethiopia, with special references to Schistosoma mansoni. AB - A parasitological survey was made in Tis Abay town, north western Ethiopia in January 1991. A total of 615 stool specimens were randomly collected from school and non-school populations. Prevalence rates for S. mansoni and other intestinal helminths were computed. Human behaviour and waste disposal were observed to be conducive for transmission of schistosomiasis and soil-transmitted parasites. From the findings of this preliminary survey it is suggested that improvement of sanitary conditions and provision of a piped water supply to all households may reduce transmission of soil and water-borne infections. PMID- 8513726 TI - The pattern of geriatric admissions in the medical wards at the Kenyatta National Hospital. AB - In a one year period (March 1990 to March 1991) the pattern of diseases in geriatric patients (over 60 years of age) admitted to the medical wards at Kenyatta National Hospital (KNH) was studied. In all, there were 1296 patients (M:F = 1.7:1) in this age group forming 11.5% of all admissions during the study period. 1008 (77.8%) of the geriatric patients were between 60 and 79 years of age. Most of the admissions (86.4%) were first admissions. The mean number of diseases per geriatric patient was 1.4. Hypertension and Cardiomyopathy were the commonest single diseases recorded, making up 43.9% of all diseases in this patient population. The commonest neurological diagnosis was stroke, which occurred in a setting of hypertension or cardiomyopathy in all the patients in whom it was diagnosed. The mean duration (+/- 2SD) of stay in the hospital in this patient population was 43 (+/- 19) days. Eighty eight (6.8%) of the patients died, the commonest cause of death being heart failure due to cardiomyopathy or hypertensive heart disease. It is concluded that geriatric patients form a sizeable proportion of our medical admissions and that a large proportion suffer from diseases of the cardiovascular system. It is thus recommended that further studies be carried out on the pattern of diseases in such patients and optimal management strategies for their ailments be outlined. PMID- 8513727 TI - Psychosocial complications and management of sickle cell disease. AB - Psychosocial disorders frequently complicate sickle cell disease. Psychological problems include neurotic illness, personality changes and psychotic reactions. Social problems may relate to work, marital and financial difficulties. Patients' siblings, parents and significant others may also suffer from emotional disorders. The role of nonpsychiatric medical and para-medical personnel in the identification and management of the psychosocial complications of sickle cell disease was mentioned. The need to pay more attention to preventive measures such as genetic counselling was also emphasized. PMID- 8513728 TI - Arm and head measurements in the newborn. AB - A total of 6,696 newborn infants were evaluated to investigate the trend in, and suggest the optimal time for assessment of, head circumference and mid-arm circumference (MAC) measurements. The measurements were recorded on the first, 3rd, 5th and 7th days of life and the mean values compared for significant differences. There were no significant differences between the mean values of head circumference and MAC for any two days of assessment compared. There was also no particular trend in the observed measurement during the first week of life. To guarantee prompt and appropriate management of high-risk infants, determination of these measurements at birth, and during the first 24 hours, is suggested as optimal. PMID- 8513729 TI - Determination of maturity at birth: further observations on a maturity scoring system for head circumference and mid-arm circumference. AB - Over a 3-month period, 114 infants were analysed to establish the reliability and usefulness of the maturity scoring for mid-arm circumference (MAC) and head circumference using the Dubowitz system as standard. Total maturity scores of the two methods showed highly significant correlation with gestational age. There was also a highly significant correlation between total maturity scores of both methods. The usefulness of the model was suggested by its comparable accuracy to the Dubowitz system. The model, however, was a significantly more rapid method of assessment. The clinical usefulness of the model was reinforced by its ability to distinguish between appropriately grown preterm low-birth weight (LBW) and growth retarded term LBW infants. The model is a rapid, reliable and useful method of determination of maturity at birth. PMID- 8513730 TI - Treatment of superficial burns with Naksol: experience in Hungary. AB - In the last 10 years, more than 10,000 patients were treated with "Naksol" against superficial burns in Hungary. The observations made during these treatments are summarised. Naksol is an alcoholic solution containing plant extracts. It offers a new and efficient therapeutic alternative within the limited possibilities available in the therapy of patients with superficial burns. Compared to other substances used for wound-surface treatment, "Naksol" reduces the number of hospitalization days by 5.3 and the total number of treatment days by 7.5 on average. It significantly reduces cicatrization, the incidence of anaemia and infections and, consequently, the requirement to use antibiotics. The treatment is inexpensive, effective, open and simple. PMID- 8513731 TI - Bronchopulmonary dysplasia: a case report. AB - An unusual case of an extremely low birth weight and very preterm infant who developed bronchopulmonary dysplasia is presented. She required artificial (assisted) ventilation via a manual ambubag using a maximum concentration of 60% O2. Despite previous reports implicating mechanical ventilators and elevated peak airway pressures greater than 35cm of water, our infant still developed the disease with O2 delivery from an ambubag. Outcome was favourable. At 16 1/2 months follow-up, she appeared neurologically normal, and despite her prolonged neonatal respiratory problem, had not been troubled by chest disease or hospital readmissions. The observed etiopathogenesis is worthy of consideration in the 'developing world'. PMID- 8513732 TI - Menstrual disorders in patients with chronic renal failure. AB - Forty females, age 14 to 35 years (mean 28.6 years) with chronic renal failure (CRF) were included in the study. Their menstrual patterns were noted. The function of their hypothalamo-pituitary-ovarian axis was assessed by the serum levels of follicle stimulating hormone (FSH), Luteinising hormone (LH), prolactin (PrL), estradiol (E2) and progesterone (P) at different phases of the menstrual cycle in patients who continued to have normal menses (Group 1) and at weekly intervals for six weeks in patients with menstrual disturbances (Group II). The mean hormone levels during the initial contact Luteal phase in group I were FSH 12.0 IU/L (N, 1.0-3.0 IU/L), LH 1.8IU/L (N 1.5-101U/L), PrL 652mIU/L (N, 100-600 mIU/L) mE2 160 pmol/L (N 400-1400 pmol/L) and P5 nmol/L (N 14-60 nmol/L) for group I. Corresponding values for group II were 1.2, 10.3, 250, 600 and 3.0 in relevant units. All patients (fourteen) with end stage renal disease (ESRD) had amenorrhoae. On the other hand, most patients with stable CRF (22/26) had normal menses. Following initiation of therapy (conservative or dialytic), there was no significant alteration in the hormonal profile or menstrual pattern. We conclude that other factors apart from the hormonal imbalances, may be responsible for the menstrual disturbances noted in patients with CRF. PMID- 8513733 TI - Disseminated histoplasmosis in a patient with acquired immunodeficiency syndrome (AIDS): a case report. AB - A 27 year old female with AIDS and disseminated histoplasmosis is presented. The clinical features include fever, weight loss, productive cough, splenomegaly and moderate pallor. The initial working diagnosis was pulmonary tuberculosis. The diagnosis of disseminated histoplasmosis was made terminally from bone marrow aspirate examination. Disseminated histoplasmosis with its varied clinical picture is likely to be missed in a patient with AIDS, and therefore a high index of suspicion is necessary for diagnosis. PMID- 8513734 TI - Isolated injury to the pancreas due to blunt abdominal trauma: a case report. AB - In the present report we are describing a case of acute pancreatitis resulting from blunt abdominal trauma. The case history, clinical and laboratory findings as well as Laparotomy findings indicated that acute pancreatitis in this case was caused by isolated injury to the pancreas sustained in the course of a blunt abdominal trauma. The clinical course of the case is given and the incidence and diagnostic problems are discussed. PMID- 8513735 TI - Evaluation of diprivan as an intravenous anaesthetic induction agent: experiences in Nairobi, Kenya. AB - Diprivan in its emulsion formulation as an intravenous induction agent was studied in 125 patients undergoing general anaesthesia for short duration, minor procedures, at Kenyatta National Hospital, Nairobi, Kenya. The drug was found to be effective as it caused loss of consciousness in all the studied patients within 40 seconds when injected intravenously. The induction period was associated with pain at injection site in 31.2%, some muscle movements in 15.2% and hiccups in 8.8% of all the cases. There was a significant fall in mean arterial blood pressure in all the cases at two minutes after induction of anaesthesia with no observed concomitant changes in pulse rate. PMID- 8513736 TI - Hypertonic saline solution: an effective wound dressing solution. AB - In search of a cheaper and effective dressing solution for ulcers, 53 patients presenting with various types of ulcers at the University of Port Harcourt Teaching Hospital were treated with different strengths hypertonic saline 0.3, 0.9, 1.2, 1.5, 2 and 3 osmoles. The ages of the ulcers were between 3 months and 3 years. Optimal results were obtained with solution of 1.5 mmols and above. Desloughing occurred within 2 weeks and granulation was fast and good enough for skin grafting where necessary. Healing was faster in other ulcers that were not due for grafting. PMID- 8513737 TI - The spectrum of echocardiographic findings in chronic renal failure. AB - In a six month period at the Kenyatta National Hospital, 46 patients (30 males) with chronic renal failure (CRF) and 22 healthy subjects have had a clinical and echocardiographic study of their cardiovascular systems. The patients with CRF were further classified as stable or in end stage renal disease (ESRD), the latter group requiring dialysis. Hypertension and circulatory congestion were the commonest clinical cardiovascular findings in patients with CRF. The patients with ESRD had significantly higher blood urea nitrogen and serum creatinine than the ones with stable CRF. Echocardiographically right ventricular size, left atrial size, aortic root diameter, left ventricular internal diameters, left ventricular end diastolic and systolic volumes, stroke volume, cardiac output, left ventricular posterior wall and interventricular septal thickness, ejection time and mitral and aortic peak flow rates were significantly higher in patients with CRF than in controls. In contrast, the circumferential fibre shortening and the ejection fraction were reduced in patients with CRF. Global left ventricular dysfunction was found in 47.8% of the patients. Using doppler flow studies, valvular incompetence was detected in a number of patients, mitral regurgitation being found in 84%.76% of the patients with CRF had varying degrees of pericardial effusion. The echocardiographic abnormalities and the pericardial effusions responded six weeks of haemodialysis in a variable manner. PMID- 8513738 TI - Kidney histology and clinical correlates in malignant hypertension. AB - In this clinico-pathologic study, post-mortem kidney material from 30 cases with malignant hypertension (MHT) defined as severe hypertension with bilateral retinal haemorrhages and exudates (grade III retinopathy) with (grade IV retinopathy) or without papilloedema, were studied. Mucoid intimal proliferation (MIP) in interlobular artery and ischaemic collapse of the glomerular tufts occurred in all cases, whereas fibrinoid necrosis (FN) was seen in only 24 (80%) of the cases. FN was not correlated nor associated with sex, age, blood pressure, retinopathy or serum creatinine. Tubular atrophy and interstitial fibrosis occurred in 24 (80%) and correlated best (rS = 0.8, p < 0.05) with serum creatinine in comparison to glomerular sclerosis (rS = 0.6, p = n.s), fibrinoid necrosis (rS = 0.49, p = n.s) and epithelial crescents (rS = 0.43, p = n.s). This study provides histologic evidence of lack of difference between grades III and IV retinopathy, shows MIP as the more characteristic vascular lesion in MHT and also, good correlation between renal function and tubulointerstitial involvement. PMID- 8513739 TI - Clinical surprises and challenges of severe malaria at Kenyatta National Hospital, Kenya. AB - While conducting a clinical trial study from July, 1989 to February 1990, we noted with surprise some clinically challenging manifestations of severe falciparum malaria at Kenyatta National Hospital, Kenya. Of the 33 cases we studied, this paper summarises two fatal cases of malaria, one case presenting with hyperglycaemia and one with severe anaemia. PMID- 8513740 TI - Abdominal injuries in children at Muhimbili Medical Centre Dar es Salaam. AB - Fifty two consecutive children with abdominal trauma who were admitted and managed at the Paediatric Surgical Unit (PSU) of Muhimbili Medical Centre (MMC) between January 1987 and December 1990 were studied. There were 35 boys and 17 girls with ages ranging from 1 year to 11 years. Most of the children came from the mostly populated areas of Dar es Salaam. The commonest causes of injury were traffic accidents (57.7%), followed by falls (32.7%). All patients due to traffic motor accidents were pedestrians except two. Forty (77%) patients had blunt abdominal injuries while 12 (23%) patients had penetrating abdominal injuries. Of these patients with peritoneal penetration only two had significant vascular injury. All patients presented with specific signs of abdominal trauma. The commonest specific organ injured was the spleen followed by the liver. The mortality was 7.6%. Associated injuries were noted in 32.6% of the cases. PMID- 8513741 TI - Total anomalous pulmonary venous drainage. AB - A case of a Nigerian full-term infant with complete anomalous pulmonary venous drainage into the coronary sinus is described. Presentation was from birth but the cardiac defect was clinically suspected at the age of 51 hours. Diagnosis was confirmed by two-dimensional echocardiography and cardiac catheterization. Despite a high operative mortality associated with this condition, the infant had a remarkably smooth post operative course and an excellent result from his repair on the 5th day of his life. PMID- 8513742 TI - Oral hygiene and dental health. PMID- 8513743 TI - Oral hygiene habits and dental health awareness of Kenyan children aged 9-15 years in a peri-urban and urban school. AB - The oral hygiene habits and dental health awareness of 541 Kenyan children from a peri-urban and urban school and aged 9-15 years, were investigated. 80.2% of the urban children and 43.1% of the peri-urban children had visited a dentist before. 12.4% of the urban children and 9.2% of the peri-urban children knew that bacteria cause dental caries. Over 87% of the children from either school knew that dental caries and periodontitis can be prevented. The main reason for visiting a dentist was to have tooth extraction. Failure to brush teeth was believed to be the cause of gingival bleeding by 38.9% of the peri-urban children and 37.6% of the urban children. 67.2% of the peri-urban children and 39.5% of the urban children brushed their teeth thrice daily. 21.1% of the peri-urban children and 2% of the urban children used a chewing stick to brush their teeth. More urban children (96.5%) used a toothbrush than peri-urban children (64.8%). None of the children from either school admitted using traditional cleaning aids such as the finger and charcoal. It is concluded that there were no consistent differences in oral hygiene habits and dental health awareness between peri-urban and urban children. PMID- 8513744 TI - Dental caries, gingivitis and dental plaque in handicapped children in Nairobi, Kenya. AB - Dental caries, gingivitis and plaque experience in 449 handicapped children aged 5-15 years attending special schools in Nairobi were determined. An intervention programme to assess oral hygiene status was also instituted. Caries was found in 198 (44%) of these children with a mean DMFT of 0.8. The severity of caries increased with age. Gingivitis was found in 166 (37%) of the children while plaque was present in all sites examined. After treatment during intervention programme, there was marked reduction in the number of sites affected by gingivitis and those with plaque, showing that it is possible to institute a cheap and effective oral health programme in schools. PMID- 8513745 TI - Dental caries and fluorides in relation to fixed orthodontic treatment: a review. AB - This paper reviews the cariological aspects of fixed orthodontic treatment and discusses the role played by topical fluorides. During fixed orthodontic treatment, carious lesions may occur in the form of white spots. These may constitute an aesthetic problem. The clinical management of white spot lesions remains unresolved. In order to prevent development of these lesions, the use of topical fluorides is advocated. The need for patient co-operation in the use of self-administered topical fluorides is critical. To reduce this critical need, the use of fluoride-releasing orthodontic cements is recommended. The literature suggests that calcium fluoride, which is the major reaction product on enamel during topical fluoride application, plays an important role in the cariostatic mechanism. PMID- 8513746 TI - The microbial aetiology of summer paediatric gastroenteritis at Ga-Rankuwa Hospital in South Africa. AB - Stool material from seventy-eight children below the age of three years was examined for the presence of various enteropathogens. The patients had been admitted to the Ga-Rankuwa hospital for rehydration therapy. A causative agent was identified in 76.9% of the cases studied. The most prevalent organisms identified were 38.5% entero-toxigenic Escherichia coli (ETEC), 25.6% Cryptosporidium parvum, 15.4% Campylobacter sp., 14.1% enteric adenoviruses and 12.8% rotavirus. In 38.5% of cases, a mixed infection was observed with up to four different organisms being identified from a single patient. ETEC elaborating heat-labile toxin (LT) found together with C. parvum was the most common combination seen in mixed infections. PMID- 8513747 TI - Attitudes of males on contraception: a KAPE survey. AB - Acceptance of Family Planning services has been at a very slow pace in Africa. It was generally believed that the African male, due to his conservatism, was an obstacle to the acceptance of contraception by the African female. The study however showed that this was not true. The attitude of the African male towards contraception has changed drastically during the last thirty years, from ultra conservatism during the 60s to very liberal in the 80s and 90s. Further it can be said that the African male is as well informed and has the same degree of Family Planning and child spacing acceptance-level as his counterpart in the developed world. However the African male does not accompany his partner for Family Planning Counselling. The study showed that most African men associate Family Planning with the use of condoms and not other methods such as the pill or the intrauterine devices. PMID- 8513748 TI - Pregnancy outcome and placental weights: their relationship to HIV-1 infection. AB - The relationship between placental characteristics, including weight and inflammation, and pregnancy outcome was examined as part of a case control study looking into the impact of maternal HIV-1 infection on pregnancy outcome. Cases defined as low birth weight (< 2500g) or stillbirth deliveries, were compared to controls defined as mothers who delivered a live born neonate weighing 2500g or more. The mean placental weight and the mean foetal/placental weight ratio were significantly lower in cases (n = 253) than in controls (n = 216) (p < .05). Placental inflammation (chorioamnionitis) was significantly associated with prematurity (p < .001) and with stillbirth (p < .05), maternal HIV-1 antibody being a risk factor for chorioamnionitis in the preterm group. These data support a correlation between placental weight and pregnancy outcome, and suggest that maternal HIV-1 infection is a risk factor for chorioamnionitis in HIV-1 seropositive preterm deliveries. PMID- 8513749 TI - Pharmacokinetic interaction of single doses of quinine and carbamazepine, phenobarbitone and phenytoin in healthy volunteers. AB - Effects of single doses of quinine on plasma and urine concentrations of carbamazepine, phenobarbitone and phenytoin were studied in healthy volunteers. Quinine (600mg, p.o.) markedly augmented the peak plasma concentrations and area under the curve (AUC [0-24]) values of carbamazepine (200mg,p.o.) and phenobarbitone (120mg,p.o.) but did not affect those of phenytoin (200mg,p.o.). Mean urinary recoveries of carbamazepine, phenobarbitone and phenytoin over 24 hours also profoundly increased with concomitant administration of quinine. These results indicate possible interaction between quinine and carbamazepine or phenobarbitone. PMID- 8513750 TI - Perception of hospital pharmacists/dispensing personnel of the essential drugs concepts (EDC) in Zimbabwe. AB - The perception of hospital pharmacists/dispensing personnel on the essential drugs concept in Zimbabwe was prospectively evaluated. To this end, 100 ad hoc questionnaires were mailed to the health professional cadre around the country in October 1989. 54 health centres responded and these consisted of 4 central hospitals, 3 provincial, 22 general and district, 14 rural hospitals, 7 private hospitals/clinics and 4 city polyclinics. These health centres serve an estimated population of 6 million people. Of the dispensing personnel, 22% had been trained in their respective health professions after 1983, i.e. after the introduction of the essential drug concept. 65% of the respondents had a working knowledge of the essential drugs concept. Pharmacists and pharmacy technicians made up 59% of the dispensing personnel, while nurses accounted for 32%. Significantly all respondents used the Essential Drug List for Zimbabwe hand book and they thought the concept is a good one. PMID- 8513751 TI - Morphometric analysis of the effect of chloroquine on rat foetal lung maturation. AB - Pregnant Sprague-Dawley rats were injected with chloroquine phosphate (40mg/kg b. wt 1.p) in the late canalicular (day 20) and early terminal-sac (day 21) and sacrificed in the late terminal sac (day 22 = term) stage of foetal lung development. The control animal received normal saline. Morphometric evaluation of the lungs by light microscopy revealed three important exposure-related lesions. They were: (a) reduction in the volume density of parenchyma and saccular space, (b) reduction in the volume of an average saccule and, (c) an increase in the number of saccules per unit volume (Numerical Density). The observations suggest that chloroquine retards foetal lung maturation by reducing the saccular expansion which takes place immediately preterm. However, the possible practical implications are unclear. PMID- 8513752 TI - Predicting secondary structures of membrane proteins with neural networks. AB - Back-propagation, feed-forward neural networks are used to predict the secondary structures of membrane proteins whose structures are known to atomic resolution. These networks are trained on globular proteins and can predict globular protein structures having no homology to those of the training set with correlation coefficients (Ci) of 0.45, 0.32 and 0.43 for alpha-helix, beta-strand and random coil structures, respectively. When tested on membrane proteins, neural networks trained on globular proteins do, on average, correctly predict (Qi) 62%, 38% and 69% of the residues in the alpha-helix, beta-strand and random coil structures. These scores rank higher than those obtained with the currently used statistical methods and are comparable to those obtained with the joint approaches tested so far on membrane proteins. The lower success score for beta-strand as compared to the other structures suggests that the sample of beta-strand patterns contained in the training set is less representative than those of alpha-helix and random coil. Our analysis, which includes the effects of the network parameters and of the structural composition of the training set on the prediction, shows that regular patterns of secondary structures can be successfully extrapolated from globular to membrane proteins. PMID- 8513753 TI - Autocatalytic cooperativity and self-regulation of ATPase pumps in membrane active transport. AB - We investigate the effect of autocatalysis on the conformational changes of membrane pumps during active transport driven by ATP. The translocation process is described by means of an alternating access model. The usual kinetic scheme is extended by introducing autocatalytic steps and allowing for dynamic formation of enzyme complexes. The usual features of cooperative models are recovered, i.e., sigmoid shapes of flux versus concentration curves. We show also that two autocatalytic steps lead to a mechanism of inhibition by the substrate as experimentally observed for some ATPase pumps. In addition, when the formation of enzyme complexes is allowed, the model exhibits a multiple stationary states regime, which can be related to a self-regulation mechanism of the active transport in biological systems. PMID- 8513754 TI - Industrial sources of benzene exposure? PMID- 8513755 TI - Comprehensive strategies needed to study breast cancer. PMID- 8513756 TI - New EPA administrator enters debate over pesticide residues in processed foods. PMID- 8513757 TI - National Academy of Sciences enters controversy on relevance of animal toxicologic studies. PMID- 8513758 TI - Carnegie Commission advocates reorganization of federal environmental research programs. PMID- 8513759 TI - The brain-immune system connection. PMID- 8513760 TI - Setting environmental agendas: the search for common ground. PMID- 8513761 TI - The Clinton-Gore agenda: environmental pledges and economic puzzles. PMID- 8513762 TI - The use of electronic communications in environmental health research. PMID- 8513763 TI - Determination of total arsenic in environmental samples from Kumasi and Obuasi, Ghana. AB - The total arsenic content of some Ghana food and cash crops from Kumasi and Obuasi farms and markets was determined. Quantitative analysis of arsenic was also conducted on vegetation, cooked food obtained from some homes, local fish, and meat, as well as some soil and water samples. In all, 266 samples were examined. Values for Kumasi samples ranged from 0.07 to 7.20 mg/kg arsenic, whereas those for Obuasi ranged from 0.12 to 70.50 mg/kg, confirming that arsenic levels for Obuasi are much higher than those for Kumasi. PMID- 8513764 TI - Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice. AB - We examined a database of 379 long-term carcinogenicity studies in rats and mice to evaluate sex and species correlations in site-specific carcinogenic responses. Within a species, most target sites showed a strong correlation between males and females. For example, chemicals producing forestomach or liver tumors in males were likely to produce these same types of tumors in females. There was also a significant correlation between species for certain site-specific carcinogenic effects, most notably tumors of the forestomach, liver, and thyroid gland. In contrast, adrenal pheochromocytoma, preputial/clitoral gland neoplasms, and lung tumors showed no significant interspecies correlation. Many chemicals produced a syndrome of carcinogenic effects involving tumors of the skin, Zymbal gland, preputial/clitoral gland, mammary gland, and/or oral cavity. Regarding different target sites, there appeared to be a correlation between thyroid and liver tumors both within and between species. Further, all chemicals producing mesotheliomas in male rats also produced mammary gland neoplasms in female rats. In contrast, kidney and urinary bladder tumors showed no significant association with any other tumor type in rats or mice. If a chemical produced a site-specific carcinogenic effect in female rats or mice, there was approximately a 65% probability that the chemical would also be carcinogenic at that same site in males. The interspecies correlation was somewhat lower: approximately 36% of the site-specific carcinogenic effects observed in one species (rats or mice) were also observed in the other species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513765 TI - Opportunities in environmental health science research. PMID- 8513766 TI - Mechanistic relationship among mutagenicity, skin sensitization, and skin carcinogenicity. AB - Twenty organic Salmonella mutagens, seven of which (including benzo[a]pyrene) are established skin carcinogens, and one of which (2-chloroethanol) is a well defined noncarcinogen to skin, have been evaluated for skin-sensitizing activity using the local lymph node assay. The relative mutagenicity of the agents to Salmonella was also established. Fourteen of the chemicals were positive in the local lymph node assay, including the seven skin carcinogens. 2-Chloroethanol was inactive as a sensitizing agent. We suggest that a variety of factors contributes to the lack of sensitizing activity of the remaining six bacterial mutagens: extremes of intrinsic chemical reactivity, high water solubility reducing dermal translocation, and inappropriate dermal metabolism. Two reference skin sensitizing agents (an oxazolinone and fluorescein isothiocyanate) were established as in vitro clastogens after their recognition as nonmutagens to Salmonella. These data imply that mutagenicity, rather than simply activity in the Salmonella assay, is a primary stimulus for electrophilic sensitization and carcinogenic initiation in the skin. We conclude that genotoxicity data for an agent can provide indications of the agent's potential to induce skin sensitization and that genotoxins which are skin-sensitizing agents have an enhanced potential to initiate skin carcinogenesis. We suggest that common, albeit individually distinct, structure-activity relationships underpin genotoxicity, skin sensitization, and the initiation of skin carcinogenesis. These relationships should simplify the hazard evaluation of chemicals and contribute to a reduction in animal usage. Several predictions of skin carcinogenicity are made based on the data presented. PMID- 8513767 TI - Characterization of in vivo somatic mutations at the hypoxanthine phosphoribosyltransferase gene of a human control population. AB - The ability to recognize a change in mutation spectrum after an exposure to a toxic substance and then relate that exposure to health risk depends on the knowledge of mutations that occur in the absence of exposure. Toward this end, we have been studying both the frequency and molecular nature of mutations of the hypoxanthine phosphoribosyltransferase (hprt) gene in peripheral blood lymphocytes as surrogate reporters of genetic damage. We have analyzed mutants, one per donor to ensure independence, from a control population in which the quantitative effects of smoking and age on mutant frequency have been well defined. Analyses of cDNA and genomic DNA by polymerase chain reaction and sequencing have identified the mutations in 63 mutants, 45 from males and 18 from females, of which 34 were smokers and 29 were nonsmokers. Slightly less than half of the mutations were base substitutions; they were predominantly at GC base pairs. Different mutations at the same site indicated that there are features of the hprt polypeptide that affect the mutation spectrum. Two pairs of identical mutations indicated that there may also be hot spots. Mutations not previously reported have been detected, indicating that the mutation spectrum is only partly defined. The remainder of the mutations were deletions or insertions/duplications; deletions ranged from one base pair to complete loss of the locus. Despite a small average increase in mutant frequency for smokers, an increased proportion of base substitutions at AT base pairs in smokers (p = 0.2) hinted at a smoking-associated shift in the mutation spectrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513768 TI - Childhood cancer in relation to a modified residential wire code. AB - Several studies have found associations between wire configuration codes, a proxy for historical residential magnetic field exposure, and childhood cancer. The Wertheimer-Leeper coding method was modified by eliminating the distinction between thick and thin primaries, distinguishing only between open and spun secondaries, and reducing the number of categories from five to three. The association between the modified code and measured magnetic fields was similar to the association with the original wire code. The modified code was used to reanalyze data from a case-control study of childhood cancer in the Denver metropolitan area. In the original study, cases were diagnosed from 1976 to 1983 among children under age 15 and compared to controls selected through random digit dialing. Wire codes for the residence at diagnosis yielded imprecise elevations of two and above for very high current configuration homes or modest 1.5-fold elevations for a dichotomous wire code. In contrast, the modified Wertheimer-Leeper code generated risk estimates that were both precise and markedly elevated for the high wire code (HWC) compared to low wire code (LWC) classifications, with medium wire code (MWC) showing little or no increase in risk. High wire code yielded odds ratios of 1.9 for total cancers (95% CI: 1.1 3.2), 2.9 for leukemias (95% CI: 1.5-5.5), and 2.5 for brain cancer (95% CI: 1.1 5.5) that were not confounded by measured potential risk factors for childhood cancer. These risk estimates are larger than the dichotomized results and more precise than those from the original five-level wire code, though limitations in the original study remain, particularly potential control selection bias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513769 TI - Public health policies regarding hazardous waste sites and cigarette smoking: an argument by analogy. PMID- 8513770 TI - Physiological deactivation after two contrasting tasks at a video display terminal: learning vs repetitive data entry . AB - Two contrasting 90 min VDT work situations were simulated in the laboratory: (1) a machine-paced, repetitive data entry task; and (2) a stimulating, self-paced learning task with successive feedback. Thirty non-smoking male students (20-34 years), without previous experience of VDT work, participated individually in each condition on two consecutive days (balanced order) and in a task-free baseline condition. Self-reports and successive measurements (ambulatory recordings) of systolic and diastolic blood pressure and heart rate were obtained during work and during a subsequent 60 min period of deactivation. Urine samples were obtained after each period for the determination of catecholamines and cortisol. In the baseline condition, measurements were obtained at corresponding times of the day. As expected, the data entry task was associated with self reports of boredom, irritation, and unpleasantness; the learning task wtih alertness, interest, and ability to concentrate. Similar elevations of physiological measurements occurred in both work situations. However, differences between conditions were found after work. Following data entry, deactivation was slower in five of the six variables (significant for epinephrine). PMID- 8513771 TI - Effects of 10 h time zone changes on female flight attendants' circadian rhythms of body temperature, alertness, and visual search. AB - The aim of the study was to analyse the effects of rapid time zone changes on the circadian rhythms of flight attendants. The mean age of the 40 female subjects was 30.0 (SD = 6.9) years. Measurements of oral temperature, alertness, and visual search were performed at two hour intervals two days before the flight from Helsinki to Los Angeles, during the second and the fourth day in the USA and during the second and fourth day after the return flight to Finland. The body temperature desynchronized and the phases of the alertness and visual search rhythms shifted rapidly in the USA. After the return flight, the acrophases of the circadian rhythms delayed during the second and fourth day in Finland. During the fourth day the acrophase of alertness was 35 min and the acrophases of body temperature and visual search were 2 h 2 min and 3 h 8 min delayed, respectively. The mathematical model based on the C-, S- and W-process theory of alertness explained 25-96% of the variation of observed mean alertness of the subjects in different conditions. It is concluded that the duration of the de- and resynchronization process of the flight attendants' circadian rhythms is on the average longer than 9 days during and after round flights over ten time zones. The mean alertness of the subject can be predicted with considerable accuracy using the mathematical model. PMID- 8513772 TI - Decision-making style, driving style, and self-reported involvement in road traffic accidents. AB - In an exploratory postal survey of 711 drivers stratified by age, sex, annual mileage, and accident involvement, decision-making style was measured using a Decision-Making Questionnaire (DMQ) and driving style was assessed using a Driving Style Questionnaire (DSQ). Responses to 21 items of the DMQ formed seven independent and internally coherent dimensions according to a principal components (PC) analysis. These were labelled: control, thoroughness, instinctiveness, social resistance, hesitancy, perfectionism, and idealism. PC analysis also revealed that responses to 15 items of the DSQ formed six independent dimensions of driving style. These were labelled: speed, calmness, social resistance, focus, planning, and deviance. Multiple regression analysis indicated that drivers of 60 years and under who scored lower on thoroughness were at greater risk of a traffic accident and that this relationship was mediated by faster driving. This relationship was independent of age, sex, annual mileage and all other factors measured. In the drivers over 60 years, lower thoroughness, greater hesitancy, and faster driving were independently associated with higher accident rates independent of all other factors measured. The results provide preliminary support for the view that people import aspects of their general decision-making style into the driving situation, and that in so doing they put themselves at differential risk of having a road traffic accident. PMID- 8513773 TI - The effect of tyre pressure on the economy of cycling. AB - Cycling requires power generation to overcome gravity, air resistance, and rolling resistance. When rolling surface and rolling speed are constant for a given tyre, rolling resistance is determined by tyre inflation pressure and the combined weight (CW) of the bicycle and rider. In this study, the oxygen uptake per unit CW (VO2 x CW-1) of seven trained bicycle racers (5 men, 2 women, 24 +/- 2 years) was measured while each cycled up a 4% incline at 19.3 km.h-1 and 75 revolutions.min-1 on a motor-driven treadmill, using randomly-ordered tyre pressures of 552, 690, 827, and 965 kPa. Subjects (55.8-78.4 kg) rode their racing bicycles equipped with the same set of sew-up tyres and wheels. VO2.CW-1 was averaged over the last 3 min of a 5 min ride at each pressure. A repeated measures analysis of variance was performed and significance set at p < 0.05. VO2.CW-1 ranged from 28.1 +/- 0.6 to 28.9 +/- 0.5 ml.kg-1 x min-1 and was not significantly different between tyre pressures. We conclude that differences in rolling resistance caused by varying tyre pressure between 552 and 965 kPa, are too small to be detected physiologically. PMID- 8513774 TI - Effects of seated posture on erector spinae EMG activity during whole body vibration. AB - The purpose of this study was to evaluate the electromyographic (EMG) response of the erector spinae to whole body vibration in three different unsupported seated postures: neutral upright, forward lean, and posterior lean. Subjects were 11 healthy college-age men. EMG was collected using bipolar surface electrodes placed bilaterally over the erector spinae at the L4 level. A modified chair with attached accelerometer was affixed to an induction type vibrator. Subjects were vibrated vertically at 4.5 Hz and 6.21 m.s-2 RMS. Data were collected in each of the three postures for 30 s pre- and post-vibration and for 2 min during vibration. Mean EMG values were determined for each sampling period and compared using ANOVA. The mean value for anterior lean was significantly larger (p < 0.05) than that for posterior lean and neutral. EMG data analysed by triggered averaging showed a phase-dependent response to the vibratory cycle for the forward leaning and neutral upright postures. The results of this study indicate that the magnitude of the vibration synchronous response of the erector spinae musculature is dependent upon body posture. This response may be an important factor in the onset of muscular fatigue and the increased incidence of back disorders among individuals exposed to whole body vibration. PMID- 8513775 TI - The effects of various thicknesses of chemical protective gloves on manual dexterity. AB - This study was conducted to determine the effects on manual dexterity of the thickness of handcovering. Twelve men were timed as they performed five dexterity tests while barehanded and while wearing each of three thicknesses of chemical protective gloves, 0.18 mm, 0.36 mm, and 0.64 mm. The subjects participated in 14 sessions held on consecutive weekdays. Analysis of the data from six sessions spanning the test period yielded significant main effects (p < 0.001) of handwear and of session on all dexterity tests. Mean times were best with bare hands and poorest with the 0.64 mm gloves. Performance with the gloves improved over sessions to the extent that the results with gloves approached or surpassed performance levels achieved with the bare hands during the early sessions. Regression analyses carried out on the data from the last three sessions revealed a linear increase in times to test completion as a function of increases in thickness of the handcovering. The occurrence of damage to the gloves, in the form of punctures and tears, was inversely related to thickness. The findings suggest that selection of the thinnest glove material compatible with protection from the chemical environment and practice working with the handwear will result in relatively efficient manual performance. PMID- 8513776 TI - Occupational risk factors associated with soft tissue disorders of the shoulder: a review of recent investigations in the literature. AB - Cumulative trauma illness currently accounts for over half of all occupational illness in the United States. From 1987 to 1989 there was a 100% increase in the reported number of cases of cumulative trauma illness (Bureau of Labor Statistics 1990). Shoulder region pain ranks second only to low back and neck pain in clinical frequency, and the occurrence of occupational shoulder illness is on the rise. This paper summarizes findings of a subset of recent epidemiologic, laboratory, and field studies conducted in order to identify occupational risk factors for cumulative trauma disorders (CTDs) of the shoulder region. These studies have identified the following risk factors as being associated with particular shoulder pain syndromes: awkward or static postures, heavy work, direct load bearing, repetitive arm movements, working with hands above shoulder height, and lack of rest. The paper begins with a discussion of several shoulder disorders, includes problems in studying cumulative trauma, presents results of recent studies, and concludes with suggested ergonomic controls that could help to reduce the incidence of shoulder disorders, by eliminating or reducing exposure to the associated risk factors. PMID- 8513777 TI - The slowing of visual processing by hypoxia. AB - An additive factors method (AFM) experiment was undertaken to determine whether the preprocessing and identification stages of information processing are implicated in the slowing of reaction time (RT) by hypoxia. The subjects (n = 14) responded at two levels of light intensity to pairs of lines that differed in length while breathing a low oxygen mixture that produced arterial oxyhaemoglobin saturations ranging between 64%-66%. The results showed a relatively large interaction between light intensity and hypoxia that was interpreted as evidence for slowing of the preprocessing stage. Differences in line length were plotted in terms of Crossman's confusion function and relatively small interactions with both hypoxia and light intensity were found, reflecting increases in slope. The light intensity x confusion level interaction was interpreted as evidence that AFM assumptions may not have been met completely in this experiment. This leads to the possibility that hypoxia slowed the identification stage indirectly rather than directly, although the latter hypothesis cannot be ruled out entirely at present. It is argued that visual slowing probably plays an important role in the disruption of perceptual-motor tasks by hypoxia. PMID- 8513778 TI - Clinical features, complications and mortality in type 2 (non-insulin dependent) diabetic patients in Addis Abeba, Ethiopia, 1976-1990. AB - Clinical features and prognosis in 1386 consecutively registered Ethiopian Type 2 (non-insulin-dependent) diabetic patients seen between 1976 and 1990 in the Diabetic Clinic in Yekatit 12 Hospital in Addis Abeba, Ethiopia, are described. Of the 1386, 52% (95% confidence interval CI 2%) were diagnosed diabetic between the ages of 40 and 59, and only 7% CI 1.4%) at age 60 or more. 51% have always been treated with oral hypoglycaemic agents, 5% with diet alone, 8% (CI 1.4%) with insulin within one year of diagnosis, and 26% (CI 2%) after varying durations on tablets. In marked contrast to the leanness of the general Ethiopian population, 53% (CI 5%) of the 408 women who knew their previous body weight had body mass index (BMI) of > 29.9 kg/m2 before the onset of diabetes, and a further 35% (CI 5%) BMI of 25.0 to 29.9; corresponding figures for 568 men were 14% (CI 3%) and 52% (CI 4%). Of the 1386, 23% (CI 3%) knew of at least one diabetic relative. Hypertension was present in 24%, in a quarter of whom it was associated with nephropathy. At last visit, 15% (CI 1%) were known to have diabetic retinopathy, 9.2% (CI 1.5%) nephropathy and 10.5% (CI 1.6%) neuropathy, all three commoner with long duration of diabetes. During the 15 years, 12% of these patients have died, with mean duration of known diabetes at death of 12.5 (CI 1.5) years. Mean age at death was 56.1 (CI 3.3) in women and 57.6 (CI 2.6) in men. The overall mortality rate was 14.9 per 1000 person-years of diabetes. Multivariate survival time analysis found 5 year survival from diagnosis of diabetes of 97% (CI 6%), 12 year survival of 65% (CI 9%) and 20 year survival of 70% (CI 7%). PMID- 8513779 TI - Effect of ivermectin treatment on microfilarial load in patients with Onchocerca volvulus in Bebeka, Ethiopia. AB - In April 1990, one hundred ninety people from Bebeka Coffee Plantation, Kefa administrative region, western Ethiopia, all with moderate to heavy infection with Onchocerca volvulus were treated with ivermectin (150 mcg/kg body wt.). Clinical examination and microfilarial counts in skin snips were repeated at intervals for eight months. Therapy was associated with minimal side effects. Significant difference in mean microfilarial load was observed throughout the eight months post-treatment period. Difference in repopulation of microfilariae between four and eight months was not significant in either sex and all ages. Of all cases, 71 (37.5%) maintained zero microfilarial counts after four months, while only 38 (20%) remained at zero level until the end of eight months. The merit of a yearly treatment programme is discussed. PMID- 8513780 TI - Evaluation of reagent strips for detection of Schistosoma haematobium infection in the lower Awash valley, Ethiopia. AB - The use of reagent strips as indirect morbidity indicators in Schistosoma haematobium infection has been assessed in comparison with urine filtration technique in the lower Awash valley of Ethiopia in 1991. The prevalence of infection by reagent sticks and urine filtration was 16.0% and 3.6%, respectively. Reagent stick haematuria was highly related with urine filtration at the 2+ limit rather than the 1+ limit. A strong association was also obtained between prevalence rate and intensity of infection of all children at both haematuria limits. The prevalence of haematuria was not sex-related but there was age-associated infection and the prevalence was highest in the 10-13 year age group. The possible use of reagent stick haematuria in the monitoring of S. haematobium infection in Ethiopia is discussed. PMID- 8513781 TI - The prune belly syndrome: triad syndrome. AB - The prune belly syndrome is described in a 2 month old male infant who presented with abdominal distension since birth to Paediatrics Department, Gonder College of Medical Science Hospital, in November 1991. The clinical and radiological presentations and theories concerning the genesis of the syndrome are briefly discussed with a review of the literature. PMID- 8513782 TI - Skin lesions in resettled and indigenous populations in Gambela, with special emphasis on the epidemiology of tropical ulcer. AB - An epidemiological survey of skin lesions was conducted in 1990 in Gambela Resettlement Scheme, Gambela, Ethiopia, as part of health status assessment of the resettlers. From seven resettlers and 3 indigenous villages, a sample population of 921 were selected by two stage random sampling. The overall prevalence rate of skin lesions was 11.5% in the resettlers and 16.0% in the indigenous population. The most prevalent type of skin lesion was ulcer in the lower limbs, with an overall prevalence rate of 6.3% and 7.4% in the resettled and indigenous population, respectively. The ulcers predominantly affected males and the age group 6 to 14 years. In this study, specific aetiology of the ulcer is not established but its clinical and epidemiological features were most compatible with those of tropical ulcer. Previous reports on leg ulcer, from resettlement schemes in Gambela and Welega, and observations made in refugee camps in Gambela, are also discussed. PMID- 8513783 TI - Suicide attempts in Ethiopian adolescents in Addis Abeba high schools. AB - Suicide is currently recognized as one of the leading causes of death of adolescents and young adults worldwide. A representative sample of all high school students in Addis Abeba in 1989/90 academic calendar was surveyed to estimate life-time prevalence and risk factors of suicide attempts. 14.3% of the adolescents reported having attempted suicide. 17.5% usually felt hopeless. Suicide attempts were strongly and linearly associated with hopelessness, grade, and heavy alcohol intake. No significant associations were observed between attempts and age, sex, family history of suicide or parental educational level. It is concluded that a substantial proportion of adolescents attempt suicide and also exhibit the risk factors. PMID- 8513785 TI - Neonatal tetanus mortality survey, north and south Omo administrative regions, Ethiopia. AB - Neonatal tetanus (NNT) is the second most frequent cause of infant mortality among the six vaccine preventable infections in developing countries. However, lack of reliable data has largely obscured the importance of the problem in these countries. A community based NNT mortality survey was conducted, using cluster sample method developed by WHO/EPI, in August 1989 in North and South Omo, Ethiopia. The study found 14 neonatal tetanus deaths among 2100 live births which occurred from 15 July 1988 to 15 July 1989, giving NNT mortality rate of 6.7/1000 LB (live births) and an estimated incidence rate of 8.4/1000 LB, accounting for 40% of all neonatal deaths. Male newborns were 2.5 times more commonly affected than females. Cutting of umbilical cord with unsterile instrument, home delivery attended by untrained TBAs, and lack of adequate tetanus TT immunization were found to be associated with increased incidence of NNT. Acceleration and promotion of TT immunization of all women of child bearing age and training of TBAs in proper obstetric care, coupled with continuous supportive supervision, is recommended in order to successfully execute the NNT elimination initiative undertaken by the Ministry of Health. PMID- 8513784 TI - Fate of Salmonella enteritidis and Salmonella typhimurium during the fermentation of ergo, a traditional Ethiopian sour milk. AB - The growth potential of Salmonella enteritidis and Salmonella typhimurium in milk in smoked and non-smoked containers and their inhibition by lactic acid bacteria was determined. In the absence of lactic acid bacteria, both Salmonella strains could grow to the level of 10(8) cfu/ml within 12 h. Smoking of containers significantly retarded Salmonella growth only until 12 h. Growth of lactic acid bacteria in souring milk retarded growth of Salmonella strains and complete inhibition was observed between 48 and 60 h at pH and titratable acidity values of 3.7 and 0.70%, respectively. The synergistic effect of lower pH, acids and smoking was important in the complete inhibition of the test organisms. Although ergo was preferably consumed after 24 h of fermentation, the Salmonella strains were not completely inhibited at this time. Thus, traditional making of ergo by the natural fermentation of raw milk could be hazardous to health. The use of a three-day old ergo as a starter for boiled milk is recommended to ensure the wholesomeness of ergo. PMID- 8513786 TI - Intermediate filaments: regulation of gene expression and assembly. PMID- 8513787 TI - Structural features of the human gene for muscle-specific enolase. Differential splicing in the 5'-untranslated sequence generates two forms of mRNA. AB - We report here the isolation and characterization of the human gene for the beta or muscle-specific isoform of the glycolytic enzyme enolase. The nucleotide sequence analysis revealed structural features, such as organization as 11 coding exons, the first exon consisting of an untranslated sequence and hence resembling sequences of the other two members of the gene family, the alpha and gamma enolase genes. The beta enolase locus spans about 6 kbp genomic DNA. Sequences matching the consensus sequence for muscle-specific regulatory factors are present in the 5'-flanking region and within the first intron. A combination of primer extension, S1 nuclease protection and RNA-sequencing experiments indicates that the gene has a unique transcriptional start site, 26 bp downstream of a TATA like box; the differential usage of two donor sites within the untranslated exon I generates two alternatively spliced transcripts. The existence of the two mRNA, differing from one another in the presence or absence of a 42-nucleotide fragment in the leader sequence, was confirmed by cloning the corresponding cDNA using the rapid amplification of cDNA ends strategy. Secondary-structure predictions indicated that the leader sequences of the spliced forms could form hairpin structures with different free energies of formation, suggesting translational control. PMID- 8513788 TI - Sequential assignment of proton resonances in the NMR spectrum of Zn-substituted alpha chains from human hemoglobin. Ligand-induced tertiary changes in the heme pocket. AB - We constructed an artificial holoprotein as a complex between alpha globin from human adult hemoglobin and the protoporphyrin IX-Zn(II). The prosthetic group is bound in a single conformation to the apoglobin via a coordinative bond between Zn(II) ion and the proximal histidine (His87). The complex is diamagnetic and does not bind either CO nor O2 thus representing a diamagnetic model of deoxygenated alpha chains. In the present paper we report extensive resonance assignment in the proton nuclear magnetic resonance spectrum of the Zn substituted alpha chains in phosphate buffer pH 5.6. A large number of aromatic and aliphatic side chain spin systems were identified in the two-dimensional homonuclear COSY spectra. Based on the assigned resonances of heme substituent protons and their NOE cross-peaks, we assigned the majority of resonances representing the heme pocket side chains. Using the main-chain-directed assignment strategy, we could establish several continuous patterns of sequential assignment and identify partial or total spin systems for a large number of side chains. The final assignment corresponds to 73% of the amino acids. Analysis of chemical shift of assigned resonances and of nuclear Overhauser enhancement connectivities provides structural information on the global and local tertiary conformation in solution and on the ligand-induced conformational changes. Comparison of observed and calculated ring current shifts enabled us to compare the solution structure with the X-ray crystal structure of alpha subunits in deoxy and carbonmonoxy hemoglobin. The global tertiary structure of unliganded chains is highly similar to both ligand and unliganded counterparts in the crystalline state. On the distal side of the heme pocket. Val62 is significantly closer to the heme center, in agreement with its conformation in the crystallographic structure. In contrast, the position of the proximal histidine (His87) relative to the heme is clearly more closely related to that in the liganded tetramer in the crystalline state. Comparison of the chemical shift values for the resonances in carbon monoxy and Zn(II)-substituted alpha chains indicates that the ligand-induced conformational changes are essentially localized in the heme pocket area and affect proximal side residues more than the distal side ones. Some notable spectral changes are discussed in connection with the crystallographic data and their relevance for the functional mechanism. PMID- 8513789 TI - Structure of a novel glycopeptidolipid antigen containing a O-methylated serine isolated from Mycobacterium xenopi. Complete 1H-NMR and 13C-NMR assignment. AB - GPL X-1, a novel glycopeptidolipid (GPL) isolated from Mycobacterium xenopi (CIPT 140 35004), has recently been found to typify a new class of mycobacterial glycopeptidolipids devoid of C-mycoside core structure, the so-called serine containing glycopeptidolipid [Riviere, M. & Puzo, G. (1991) J. Biol. Chem. 266, 9057-9063]. Here we report the purification and characterization of a novel serine-containing GPL termed GPL X-IIb, isolated from the M. xenopi strain NCTC 10042. On thin-layer chromatography, this GPL was found to be present in some other M. xenopi strains isolated from patients with pulmonary infections. The sugar and amino-acid compositions of this GPL were elucidated from the native form using a combination of two-dimensional homonuclear and heteronuclear scalar coupling NMR. The peptide and sugar sequences, as well as the methoxyl group locations on the C-3 of the 6-deoxy-alpha-L-talopyranoside (6dTalp) and on a Ser, were unambiguously determined by heteronuclear multiple-bond correlation experiments. GPL X-IIb was found to be composed of a lipotetrapeptide of the following structure C12-Ser-OMe-Ser-Phe-aThr-OMe (aThr = allothreonine). The sugar part is made up of 3OMe-alpha-L-6dTalp and the following disaccharide: alpha-L-Rhap-(1-->3)-2-O-Lau-alpha-L-Rhap (Rhap = rhanmopyranose). Unlike GPL X I, the sugar attachment sites on the tetrapeptide were successfully determined from heteronuclear three-bond coupling correlation observed in the heteronuclear multiple bond correlation spectrum between the anomeric carbon resonances and the beta protons of aThr-OMe and Ser. It was established that the 3OMe-6dTalp glycosylates the Ser while the disaccharide is linked to the aThr-OMe. Thus both GPL X-I and GPL X-IIb share a common lipotetrapeptide core [with the exception of Ser(OMe)] but drastically differ in their oligosaccharide appendage. Thus, by analogy with the M. avium complex, the present report suggests that M. xenopi species can be divided in various serovars characterized by the unique structure of their C-mycoside GPL oligosaccharide appendage, enhancing the interest for this new type of serine-containing glycopeptidolipid. PMID- 8513790 TI - Trimethylphosphine binding to horse-heart and sperm-whale myoglobins. Kinetics, proton magnetic resonance assignment and nuclear Overhauser effect investigation of the heme pocket. AB - Two-dimensional nuclear magnetic resonance techniques have been used to assign resonances corresponding to the heme pocket and several other residues of horse heart and sperm whale myoglobins ligated by trimethylphosphine. The assignment procedure was based mainly on the nuclear Overhauser effect connectivities with the ligand and the heme substituents. For quantitative measurements of Overhauser effects, application of truncated driven techniques between a proton from distal residues and methyl groups from the ligand was used to determine internuclear distances. These new results have permitted us to map the heme pockets and to investigate the conformational differences in the heme pockets between horse heart and sperm whale myoglobins. The interproton distances between distal amino acid residues and trimethylphosphine were found to be longer in horse heart myoglobin relative to those in sperm whale myoglobin. This result suggests that the size of the heme pocket is larger in horse heart myoglobin. Association and dissociation rate constants were measured for trimethylphosphine binding to myoglobins. Both values were four times larger for horse heart myoglobin than those for sperm whale myoglobin. This observation confirms the structural results obtained with NMR studies and is rationalized by a greater stabilization of a larger pocket in horse heart myoglobin relative to sperm whale myoglobin. PMID- 8513791 TI - The solution structure of the leucine zipper motif of the Jun oncoprotein homodimer. AB - Proton NMR studies have been performed on a 9.8-kDa synthetic fragment comprising the homodimeric leucine zipper domain of the human oncoprotein Jun to ascertain its conformation in aqueous solution. Analysis of two-dimensional scalar and dipolar-coupling experiments enabled almost all proton resonances to be sequence specifically assigned and further revealed that the Jun leucine zipper forms a completely symmetric dimer in solution, consistent with the formation of a coiled coil arrangement of parallel alpha-helical strands. The rates of exchange of individual amide protons with solvent, as well as hydrogen-bond lengths predicted from amide proton chemical shifts, are shown to correlate with residue position in the coiled-coil. A subset of 209 unambiguous distance constraints was compiled using rules recently formulated for interpreting the NOESY spectra of symmetric coiled-coils, and these were used in combination with experimentally determined hydrogen bond and dihedral angle constraints to compute a solution structure for the Jun leucine zipper domain. PMID- 8513792 TI - Determination of the sequence requirements for the expression of a Xenopus borealis embryonic/larval skeletal actin gene. AB - In this study, we demonstrate that all sequences necessary and sufficient for the expression of a Xenopus borealis alpha 3B embryonic/larval skeletal actin gene, reside in a 156-nucleotide fragment of the promoter that spans nucleotides -197 to -42. This region of the promoter contains three imperfect repeats of the CC(A/T)6GG (CArG) box motif that have been demonstrated to be important in the expression of other sarcomeric actin genes. Deletion of the actin promoter, using Xenopus microinjection techniques as a transient assay system for promoter activity, shows that the most distal CArG box (CArG box 3) is essential for the full expression of the gene. Under our assay conditions, the most proximal CArG box (CArG box 1) exhibits two binding activities using bandshift analysis. One of these binding activities contains components antigenically related to a serum response factor (transcription factor), whilst the second does not. In contrast, CArG box3 produces only a single retarded band using electrophoretic mobility shift analysis. Although the shifted complex coelectrophoreses with the CArG box 1/serum-response factor complex, the band produced by CArG box3 appears to be distinct from SRF. In addition to the CArG motifs, a further upstream regulatory element has been identified in the actin promoter between nucleotides -197 and 167. In the actin promoter, a downstream region can apparently fulfil this function. PMID- 8513793 TI - The structural characterization and bilirubin-binding properties of albumin Herborn, a [Lys240-->Glu] albumin mutant. AB - We report the molecular defect of albumin Herborn, a new genetic variant of human serum albumin which has been found in Germany. Isoelectric focusing analysis of CNBr fragments from the purified variant allowed us to localize the mutation in fragment CNBr 3 (residues 124-298). This fragment was isolated on a preparative scale and subjected to tryptic and V8 protease digestion. Sequence determination of the abnormal tryptic and V8 peptides revealed that the variant arises from the substitution Lys240-->Glu. The -2 charge change of albumin Herborn, which is probably due to a A-->G transition in the first position of the corresponding codon in the structural gene, has no significant effect on its electrophoretic mobility under non-denaturating conditions. Therefore we have assumed that residue 240, which has been implicated in the bilirubin primary binding site (Jacobsen, C. (1978) Biochem. J. 171, 453-459), is buried. The binding of bilirubin and biliverdin by albumin Herborn was quantified using the fluorescence quenching method. The apparent equilibrium association constants (Ka +/- SD) and the number of high-affinity binding sites (n) of the defatted variant for bilirubin and biliverdin were Ka = 1.03 +/- 0.18 x 10(8) M-1, n = 1.07; and Ka = 7.48 +/- 1.10 x 10(6) M-1, n = 1.01, respectively. The Ka values are about 93.3% and 99.1% of the values found for the normal protein under the same conditions. These results strongly suggest that Lys240 of human serum albumin is not the basic residue involved in ion pairing with one of the carboxylate groups of bilirubin at its high-affinity site. PMID- 8513794 TI - Amino acid sequence of the human intermediate basic protein 2 (HPI2) from sperm nuclei. Structural relationship with protamine P2. AB - Human intermediate basic protein 2 (HPI2) is a low-molecular-mass basic protein present in small amounts in human sperm nuclei. The amino acid composition of the protein, its N-terminal amino acid sequence and peptide maps obtained after digestion with endoproteinases Lys-C and Glu-C, reveal that HPI2 is structurally related to human protamine species P2 (HP2), which is rich in Arg, His and Cys residues. Compared to HP2, which is one of the two major sperm protamines, HPI2 has an N-terminal extension of 24 residues which includes six acidic residues and does not possess any Arg residues. The amino acid sequence of HPI2 (81 residues) is identical to the sequence of the C-terminal region of another minor sperm nuclear protein, human intermediate basic protein 1 (HPI1, 101 residues), which was sequenced previously [Martinage, A., Arkhis, A., Alimi, E., Sautiere, P. & Chevaillier, P. (1990) Eur. J. Biochem. 191, 449-451]. Due to this structural similarity, HPI2 must be considered as an intermediate in the maturation of proprotamine HPI1 limited proteolysis. PMID- 8513795 TI - Oligomerization of the Nef protein from human immunodeficiency virus (HIV) type 1. AB - The nef genes, derived from two different human immunodeficiency-virus-type-1 (HIV-1) strains, were expressed in procaryotic cells (Escherichia coli) and in eucaryotic cells (insect cells infected with nef-containing baculovirus). The oligomerization of recombinant Nef protein was studied by NMR spectroscopy and immunoblotting under various experimental conditions. 1H-NMR spectroscopy shows that native folded protein has the tendency to polymerize under low-salt conditions. These oligomers become covalently linked by disulfide bonds after decreasing the reduction potential, a process which is fully reversible. Cross linking studies with bis(sulfo-succinimidyl)suberate and alkylation with iodoacetic acid under non-reducing and reducing conditions document for the first time that Nef can also form homomeric structures including monomers, dimers, trimers and tetramers in cell lysates and intact cells. We found disulfide-linked as well as non-covalently associated oligomers. Since the Nef molecules are not exclusively found in the cytoplasm of HIV infected cells and since the reduced glutathione concentration in lymphocytes of virus infected persons is known to be unusually low, it might be possible that these Nef oligomers have a biological function in vivo as well. PMID- 8513796 TI - Gamma-phosphate-linked ATP-sepharose for the affinity purification of protein kinases. Rapid purification to homogeneity of skeletal muscle mitogen-activated protein kinase kinase. AB - Recently, Sowadski and colleagues [Knighton, D.R., Zheng, J., Eyck, L.F.T., Ashford, V.A., Xuong, N., Taylor, S.S. & Sowadski, J.M. (1991) Science 407, 407 420] reported the structure of a ternary complex of the catalytic subunit of cAMP dependent protein kinase (cyclic A kinase), MgATP and a 20-residue inhibitor peptide, at a resolution of 0.27 nm. This structure has since been refined to 0.2 nm resolution and the orientation of the nucleotide and interactions of MgATP with numerous conserved residues at the active site defined [Zheng, J., Knighton, D.R., Eyck, L.F.T., Karlsson, R., Xuong, N., Taylor, S.S. & Sowadski, J.M. (1993) Biochemistry, in the press]. These studies revealed that the adenosine portion of ATP is buried deep within the catalytic cleft, with the alpha, beta and gamma phosphates protruding towards the opening of the cleft. The unique spatial positioning of MgATP within the catalytic cleft of cyclic A kinase and its interactions with conserved amino acids found in all protein kinases, led us to reconsider the use of ATP as an affinity ligand for the purification of these enzymes. In this paper, we describe a straightforward method for the synthesis of [gamma-32P]adenosine-5'-(gamma-4-aminophenyl)triphosphate for the covalent linkage of ATP to Sepharose through its gamma phosphate. In the presence of 20 microM ATP, adenosine-5'-(gamma-4-aminophenyl)triphosphate exhibited apparent Ki values of 103.6, 75.18, 176.28 and 120.00 microM against cyclic A kinase, mitogen activated protein kinase (p42mapk), mitogen-activated protein kinase kinase and p60c-src, respectively. To illustrate the effectiveness of adenosine-5'-(gamma-4 aminophenyl)triphosphate-Sepharose as an affinity column for protein kinases, we have used the resin to purify rabbit skeletal muscle mitogen-activated protein kinase kinase over 19000-fold to homogeneity. PMID- 8513797 TI - Isolation, characterization and N-terminal amino acid sequence of hydrogenase from the green alga Chlamydomonas reinhardtii. AB - Hydrogenase from Chlamydomonas reinhardtii was purified to homogeneity by five column-chromatography steps under strict anaerobic conditions. The cells were disrupted by mild treatment with detergent. The enzyme was purified 6100-fold, resulting in a specific activity for H2 evolution of 935 mumol.min-1.mg protein-1 at 25 degrees C, using reduced methyl viologen as electron donor. The optimal temperature for hydrogen evolution is 60 degrees C, the optimal pH value is 6.9. The Km value for methyl viologen is 0.83 mM, for ferredoxin, 35 microM. From SDS/PAGE gels, the protein was judged to be pure. On non-denaturing gels, run under nitrogen, a single band was detected after activity staining. This band corresponded to the single band observed on denaturing SDS gels, which had an apparent molecular mass of 48 kDa. If the band was cut out of the native gel and incubated with reduced methyl viologen, hydrogen evolution could be measured. The purified enzyme contains 4 Fe atoms/mol. The amino acid composition and the N terminal amino acid sequence (24 residues) of the protein were determined. No significant amino acid sequence homologies could be found to any sequences from prokaryotic hydrogenases. PMID- 8513798 TI - The addition of nine residues at the C-terminus of human prolactin drastically alters its biological properties. AB - We have added nine extra residues to the C-terminal of human prolactin and analysed the effect of this mutation on the ability of the hormone to bind to its lactogenic receptor and to induce Nb2 cell division. Both properties are markedly affected when compared to the natural 23-kDa human prolactin. Since no alteration of the global protein folding was detected either by circular dichroism or by infrared spectroscopy, the decrease in biological potency can be exclusively attributed to an effect of the nine additional residues on their near environment. From infrared analysis and secondary structure prediction, the elongated tail is assumed to be involved in a beta-sheet with a few residues initially belonging to the fourth helix. Moreover, from the X-ray structures of porcine and human growth hormones, two proteins homologous to prolactins, the nine extra residues are likely to fold within a concave pocket delimited by helices 1 and 4, and the second half of the loop connecting helices 1 and 2 (loop 1). Thereby, we suggest that the additional residues prevent some residues belonging to this pocket from interacting with the lactogenic receptor. This is in perfect agreement with our earlier proposal that the binding site of prolactin to the lactogenic receptor is homologous to that of growth hormone to the somatogenic receptor, i.e. essentially composed of residues belonging to this concave pocket. PMID- 8513799 TI - Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action. AB - Crotoxin from the venom of the South American rattlesnake Crotalus durissus terrificus is a potent neurotoxin consisting of a weakly toxic phospholipase-A2 subunit (CB) and a non-enzymic, non-toxic subunit (CA). Crotoxin complex (CACB) dissociates upon interaction with membranes: CB binds while CA does not. Moreover, CA enhances the toxicity of CB by preventing its non-specific adsorption. Several crotoxin isoforms have been identified. Multiple variants of each subunit give different crotoxin complexes that can be subdivided into two classes: those of high toxicity and low enzymic activity and those of moderate toxicity and a high phospholipase-A2 activity. In this study, we demonstrate that the more-toxic isoforms block neuromuscular transmission of chick biventer cervicis preparations more efficiently than weakly toxic isoforms. The less-toxic crotoxin complexes have the same Km and Vmax as CB alone. In contrast, the more toxic isoforms are enzymically less active than CB. These differences correlate with the stability of the complexes: less-toxic isoforms are less stable (Kd = 25 nM) and dissociate rapidly (half-life about 1 min), whereas the more-toxic isoforms are more stable (Kd = 4.5 nM) and dissociate more slowly (half-life 10 20 min). The rate of interaction of crotoxin complexes with vesicles of negatively charged phospholipids paralleled the rate of dissociation of the complexes in the absence of vesicles. The differences of pharmacological and biochemical properties of crotoxin isoforms indicate that the stability of crotoxin complexes plays a major role in the synergistic action of crotoxin subunits: a stronger association between the two crotoxin subunits would account for their slower dissociation rate, a weaker enzymic activity, a slower interaction with phosphatidylglycerol vesicles, a faster blockade of neuromuscular transmission and a higher lethal potency. PMID- 8513800 TI - Purification and characterization of the major tyrosine protein kinase from the human promyelocytic cell line, HL60. AB - The major tyrosine protein kinase from HL60 (a human non-differentiated promyelocytic cell line) has been purified almost to homogeneity as judged by silver-stained SDS/PAGE. The procedure involved four chromatographic steps: DEAE Sepharose, casein-agarose, cibacron-blue--agarose and hexyl-agarose. The purification resulted in more than 1000-fold enrichment in angiotensin II phosphorylation activity. A gel-sizing experiment, labeling with [35S]ATP[gamma s] and autophosphorylation of the enzyme in the presence of [gamma-32P]ATP, all led to the identification of a single protein species with a molecular mass of about 40 kDa. Western blot experiments showed that this protein does not belong to the src family and is not related to the abl and fes oncogene products. Phosphorylation of angiotensin II and casein by this 40-kDa human promyelocytic kinase was stimulated by high ionic strength especially from class IA metal salts. The Km for ATP was 2 microM and the Vmax 3.1 nmol.min-1.mg-1 using angiotensin II as a substrate. The kinase requires the presence of either Mn2+ or Mg2+ for full activity and utilizes ATP or dATP but not GTP as phosphate donor. Based on numerous biochemical observations, it was possible to demonstrate that kinase is different from any other tyrosine protein kinases described in the literature. This 40-kDa protein was used as a molecular tool for testing some tyrosine protein kinase inhibitors described in the literature. It is one of the rare tyrosine protein kinases purified from human cancer cells to date. PMID- 8513801 TI - Paracatalytic self-inactivation of fructose-1,6-bisphosphate aldolase. Structure of the crosslink formed at the active site. AB - Oxidation of enzyme-substrate carbanion intermediates by extrinsic oxidants may result in irreversible paracatalytic inactivation of certain enzymes. In paracatalytically modified fructose-1,6-bisphosphate aldolase from rabbit muscle the polypeptide chain had been found to be crosslinked at active-site Lys229 (Schiff base forming with substrate) and Lys146 by a phosphorylated three-carbon moiety [Lubini, D. G. E. and Christen, P. (1979) Proc. Natl Acad. Sci. USA 76, 2527-2531]. In the present study, the structure of this crosslink was elucidated by instrumental analysis. Aldolase was paracatalytically modified in the presence of fructose 1,6-bisphosphate and hexacyanoferrate(III). The completely inactivated enzyme was digested with pronase. The crosslinked peptide was isolated by gel filtration and reverse-phase HPLC. Mass spectroscopy, 1H- and 13C NMR showed that a derivative of dihydroxyacetone phosphate forms an amidine with the epsilon-amino groups of the two lysine residues: [formula: see text] PMID- 8513802 TI - Integration of a cyanobacterial protein involved in nitrate reduction (narB) into isolated Synechococcus but not into pea thylakoid membranes. AB - Chimeric genes comprised of Rubisco small subunit transit peptide fused in frame with full-length and truncated sequences of a nitrate reductase (narB) structural gene of Synechococcus were constructed. Fusion proteins were synthesized in a rabbit reticulocyte system. In thylakoido integration of synthetic proteins resulted in the association of the full-length narB-coded protein to the Synechococcus photosynthetic membranes. The membrane-associated protein was sensitive to trypsin treatment but could not be removed by washing in the presence of NaBr. Trypsin pretreatment of thylakoids abolished the capability for association. The association of the narB-coded protein with thylakoids might require another membrane protein whose identity is not known. It is proposed that the Synechococcus narB polypeptide is a peripheral, membrane bound protein anchored to the thylakoids via a short hydrophobic domain while the major part of the protein resides on the outer side of the thylakoid membranes. The chimeric narB proteins were processed and imported by intact pea chloroplasts in vitro; however, the mature proteins were found localized in the stroma and not in the thylakoid membrane fraction. Similarly, the attempt to integrate the protein in vitro into isolated pea thylakoid membranes failed although these membranes incorporate early light-inducible proteins. PMID- 8513803 TI - Characterisation of the ATP-dependent taurocholate-carrier protein (gp110) of the hepatocyte canalicular membrane. AB - The canalicular domain-specific glycoprotein gp110, which recently has been shown to function as an ATP-dependent taurocholate transporter, has been purified 1800 fold from rat liver plasma membranes. gp110 has been characterised as an integral plasma membrane protein with M(r) of 100,000-115,000 and pI of 2.5-3.5 and possesses a highly glycosylated and negatively charged extra-cellular domain. The broad range of M(r) and pI values results from the existence of numerous glycoforms composed of sialylated N-glycans. After deglycosylation, the polypeptide has M(r) 48,000 and pI 5.0. In primary cultures of rat hepatocytes, gp110 is synthesised with M(r) 110,000, while in the presence of tunicamycin the non-glycosylated form has M(r) 48,000. In the presence of 1-deoxymannojirimycin, two forms of M(r) 83,000 and M(r) 91,000 were found, which were converted by endo beta-N-acetylglucosaminidase H into a single 52,000-M(r) band, indicating the existence of two basic glycoforms at the oligomannosyl stage of biosynthesis. gp110 was phosphorylated at serine residues in primary cultures of hepatocytes. The sequences of ten internal peptides of gp110 were identical to the sequence of the high-M(r) form of ecto-ATPase, but ecto-ATPase activity from plasma-membrane extracts was not depleted by anti-(gp110) serum. In contrast, Fab fragments of these antibodies inhibit the aggregation of freshly isolated hepatocytes. PMID- 8513804 TI - Aminotransferases: demonstration of homology and division into evolutionary subgroups. AB - A total of 150 amino acid sequences of vitamin B6-dependent enzymes are known to date, the largest contingent being furnished by the aminotransferases with 51 sequences of 14 different enzymes. All aminotransferase sequences were aligned by using algorithms for sequence comparison, hydropathy patterns and secondary structure predictions. The aminotransferases could be divided into four subgroups on the basis of their mutual structural relatedness. Subgroup I comprises aspartate, alanine, tyrosine, histidinol-phosphate, and phenylalanine aminotransferases; subgroup II acetylornithine, ornithine, omega-amino acid, 4 aminobutyrate and diaminopelargonate aminotransferases; subgroup III D-alanine and branched-chain amino acid aminotransferases, and subgroup IV serine and phosphoserine aminotransferases. (N-1) Profile analysis, a more stringent application of profile analysis [Gribskov, M., McLachlan, A. D. and Eisenberg, D. (1987) Proc. Natl Acad. Sci. USA 84, 4355-4358], established the homology among the enzymes of each subgroup as well as among all subgroups except subgroup III. However, similarity of active-site segments and the hydropathy patterns around invariant residues suggest that subgroup III, though most distantly related, might also be homologous with the other aminotransferases. On the basis of the comprehensive alignment, a new numbering of amino acid residues applicable to aminotransferases (AT) in general is proposed. In the multiply aligned sequences, only four out of a total of about 400 amino acid residues proved invariant in all 51 sequences, i.e. Gly(314AT)197, Asp/Glu(340AT)222, Lys(385AT)258 and Arg(562AT)386, the number not in parentheses corresponding to the structure of porcine cytosolic aspartate aminotransferase. Apparently, the aminotransferases constitute a group of homologous proteins which diverged into subgroups and, with some exceptions, into substrate-specific individual enzymes already in the universal ancestor cell. PMID- 8513805 TI - Co-reconstitution of plasma membrane H(+)-ATPase from yeast and bacteriorhodopsin into liposomes. ATP hydrolysis as a function of external and internal pH. AB - The H(+)-ATPase from the plasma membrane of Saccharomyces cerevisiae was isolated and purified. The enzyme was reconstituted with bacteriorhodopsin into asolectin liposomes by detergent dialysis at a molar ratio of 1 H(+)-ATPase to 50 bacteriorhodopsins. The overall orientation of the proteins is such that proton pumping to the vesicle interior occurs upon illumination and after addition of ATP. All liposomes which contain H(+)-ATPase also contain bacteriorhodopsin. The rate of ATP hydrolysis was measured as function of pH in the dark and during illumination of the proteoliposomes. The pH dependency can be described by the protonation of a monovalent group from the outside with an apparent pK of 7.3 and the deprotonation of a monovalent group at the inside with an apparent pK of 3.7. Inside and outside refer to the orientation of the H(+)-ATPase in the liposomes which is opposite to that occurring in vivo. It is concluded that the first step in the reaction cycle is the binding of a proton from the cytosol which is followed by ATP binding, ATP hydrolysis on the enzyme and the release of ADP and phosphate, and finally the proton is released from the enzyme into the external medium. PMID- 8513807 TI - Mitochondrial transport of mitoribosomal proteins, YmL8 and YmL20, in Saccharomyces cerevisiae. AB - Two mitochondrial ribosomal (mitoribosomal) proteins, YmL8 and YmL20, of the yeast Saccharomyces cerevisiae and their derivatives were synthesized in vitro and their transport into isolated yeast mitochondria was examined. Of the two proteins, YmL20 possesses an N-terminal presequence of 18 amino acid residues, while YmL8 has no such presequence. Both proteins were found to be transported into isolated mitochondria in an energy-dependent manner. Furthermore, YmL20 protein without its N-terminal presequence was also transported, despite the fact that the presequence alone was capable of transporting a fused passenger protein, Chinese hamster dihydrofolate reductase (DHFR). Therefore, YmL20 protein appears to possess redundant transport signals in its structure. Similarly, YmL8 derivatives lacking either 40 or 86 amino acid residues from the N-terminus and/or 52 amino acid residues from the C-terminus were transported. In addition, the N-terminal segment of this protein was capable of transporting Chinese hamster DHFR into mitochondria, while its C-terminal segment was not. Thus, YmL8 protein also appears to possess two or more transport signals in its structure. Perhaps the presence of many basic amino acid residues in these proteins might, at least partly, contribute to their mitochondrial transport. PMID- 8513806 TI - Different in vitro metabolism of 7 alpha-methyl-19-nortestosterone by human and equine aromatases. AB - The ability of human and equine placental microsomes to aromatize 7 alpha-methyl 19-nortestosterone (MNT) was studied. Kinetic analysis indicates that MNT shares the androgen-binding site of human and equine placental microsomal aromatases. Human placental microsomal estrogen synthetase had about a 2.5-fold higher relative affinity for MNT than the equine placental enzyme (KiMNT/Km androstenedione of 32 versus 87). However, MNT was not metabolized by human placental microsomes, whereas it was very actively metabolized by equine placental microsomes. Further studies using purified equine cytochrome P-450arom indicated that the presence of a 7 alpha-methyl group and the absence of a C19 methyl group did not impair its conversion by the purified enzyme. The product of this reaction was separated and identified as 7 alpha-methylestradiol by gas chromatography coupled to mass spectrometry. PMID- 8513808 TI - Functional reconstitution of the Trypanosoma brucei plasma-membrane D-glucose transporter. AB - The D-glucose transporter of Trypanosoma brucei was solubilized from the plasma membrane and reconstituted into proteoliposomes. Using the reconstitution of D glucose transport as the assay and non-specific L-glucose uptake as control, we have purified a membrane protein fraction from T. brucei bloodstream-form ghosts by EDTA/alkali treatment and solubilization with the detergents octylglucoside or octylthioglucoside. Upon removal of the detergent by dialysis, the solubilized protein fraction was reconstituted in sonicated liposomes by a freeze/thaw sonication step. The reconstituted transporter catalyzed specific D-glucose uptake and was compared in several characteristics with the native facilitated diffusion transporter as present in live trypanosomes [Seyfang, A. & Duszenko, M. (1991) Eur. J. Biochem. 202, 191-196]. As in vivo, the uptake is time dependent and Na+ independent. Transporter substrate affinity and inhibitor specificity are completely retained and it is inhibited by mercuric ions, phloretin and cytochalasin B, but only partially inhibited by phlorizin. The reconstituted transporter also demonstrates trans-stimulation properties indicative of the carrier-mediated transport of D-glucose. In contrast to the human erythrocyte type glucose transporter, in T. brucei D-fructose uptake was also catalyzed by the same reconstituted protein fraction and specific D-glucose or D-fructose transport were mutually competitive. Both the inhibitor studies and the fructose transport capacity in the reconstituted system are in good agreement with the native transport in live trypanosomes. The specific activity of D-glucose transport was 1.9 +/- 0.3 nmol.min-1.mg protein-1 at 0.2 mM D-glucose and the yield was about 0.8% of total ghost protein after removal of the variant-surface glycoprotein coat. The successful functional reconstitution of a protozoan glucose transporter represents an important step towards its purification and detailed characterization. This is especially interesting since bloodstream-form trypanosomes depend entirely upon glycolysis for their ATP production. PMID- 8513809 TI - Purification and characterization of the alpha-agarase from Alteromonas agarlyticus (Cataldi) comb. nov., strain GJ1B. AB - The phenotypic features of strain GJ1B, an unidentified marine bacterium that degrades agar [Young, K. S. Bhattacharjee, S. S. & Yaphe, W. (1978) Carbohydr. Res. 66, 207-212], were investigated and its agarolytic system was characterized using 13C-NMR spectroscopy to analyse the agarose degradation products. The bacterium was assigned to the genus Alteromonas and the new combination A. agarlyticus (Cataldi) is proposed. An alpha-agarase, i.e. specific for the alpha(1-->3) linkages present in agarose, was purified to homogeneity from the culture supernatant by affinity chromatography on cross-linked agarose (Sepharose CL-6B) and by anion-exchange chromatography (Mono Q column). The major end product of agarose hydrolysis using the purified enzyme was agarotetraose. Using SDS/PAGE, the purified alpha-agarase was detected as a single band with a molecular mass of 180 kDa. After the affinity-chromatography step, however, the native molecular mass was approximately 360 kDa, suggesting that the native enzyme is a dimer which is dissociated to active subunits by anion-exchange chromatography. The isolectric point was estimated to be 5.3. Enzyme activity was observed using agar as the substrate over the pH range 6.0-9.0 with a maximum value at pH 7.2 in Mops or Tris buffer. The enzyme was inactivated by prolonged treatment at a pH below 6.5, or by temperatures over 45 degrees C or by removing calcium. In addition, a beta-galactosidase specific for the end products of the alpha-agarase was present in the alpha-agarase affinity-chromatography fraction, probably as part of a complex with this enzyme. The degradation of agarose by this agarase complex yielded a mixture of oligosaccharides in the agarotetraose series and the agarotriose series, the latter consisting of oligosaccharides with an odd number of galactose residues. PMID- 8513810 TI - Evolution of pro-protamine P2 genes in primates. AB - Protamines P1 and P2 form a family of small basic peptides that represent the major sperm proteins in placental mammals. In human and mouse protamine P2 is one of the most abundant sperm proteins. The protamine P2 gene codes for a P2 precursor, pro-P2 which is later processed by proteolytic cleavages in its N terminal region to form the mature P2 protamines. We have used polymerase chain amplification to directly sequence the pro-P2 genes of the five major primate families: red howler (Alouatta seniculus) is a New World monkey (Cebidae); the two macaque species, Macaca mulatta and M. nemistrina are Old World monkeys (Cercopithecidae), the gibbon, Hylobates lar, represents one branch of the apes (Hylobatidae); the orangutan, Pongo pygmaeus, gorilla, Gorilla gorilla and two species of chimpanzee Pan paniscus and Pan troglodytes represent a second ape family (Pongidae). These pro-P2 genes are compared with that of human [Domenjoud, L., Nussbaum, G., Adham, I. M., Greeske, G. & Engel, W. (1990) Genomics 8, 127 133]. The overall size and organization of the genes are conserved within the group. The mean length of pro-P2 is 101 residues, with an increase to 102 in M. nemistrina and a decrease to 99 residues in red howler (A. seniculus). In gorilla and red howler one of two 79-bp tandem repeats that occurs 3' of the gene is deleted. Of the 101 deduced amino acids examined, an amino acid change occurs in one or more primates at 45 positions. Considering only the most recently diverged group, the human/gorilla/chimpanzee clade, this represents a very high mutation rate of 0.99 changes/100 sites in 10(6) years. This rapid mutation rate is characteristic of both members of the protamine gene family, P1 and P2. Consideration of the variable nature of the sequences at the multiple sites of proteolysis during the processing of the pro-P2 indicates either that there are several processing enzymes of differing specificities, or more likely that the folded structure of the pro-P2 limits accessibility of a non-specific protease to certain exposed sites. PMID- 8513811 TI - Enterococcal septicemia in patients with hematological malignancies. AB - Thirty-six cases of enterococcal septicemia in patients with hematological malignancies were reviewed retrospectively and categorized according to their clinical significance using strict previously described definitions. Overall, most of the infected patients were males (77%), had acute leukemia (64%), had recently received cytotoxic drug therapy (86%), were granulocytopenic at the onset of septicemia (77%), and acquired the infection during hospitalization (77%). The source of septicemia was unknown in 18 (50%) patients, intestinal in 15 (42%) and intravascular in three (8%). Mortality was 19% among 21 inpatients who had clinically significant septicemia and 30% among patients with septicemia of uncertain clinical significance. The fatal outcome could be definitively attributed to enterococcal septicemia in only one of the nine inpatients who died. Clinically significant septicemia appeared somewhat more frequently to be polymicrobial (p = 0.06), whereas septicemia of unknown significance presented more frequently as breakthrough septicemia (p = 0.013). Unless associated with intravascular infection, enterococcal septicemia in patients with hematological malignancies seems to represent a marker of cytotoxic drug damage of the intestinal mucosa rather than a truly invasive infection. PMID- 8513812 TI - Early diagnosis of typhoid fever by an enzyme immunoassay using Salmonella typhi outer membrane protein preparations. AB - An enzyme immunoassay (EIA) for detection of serum antibodies in patients with typhoid fever was developed using Salmonella typhi outer membrane protein (OMP) preparations as antigen. Acute phase (first week) sera from adult typhoid fever patients were tested as well as sera from the following control groups: adult travellers with diarrhea caused by enterotoxigenic Escherichia coli, children infected with Campylobacter jejuni, healthy Mexican adult blood donors, and adults with septicemia caused by other organisms. At a 1:3,125 serum dilution, the mean absorbance values were 1.41 in the typhoid fever patients, and 0.57, 0.55, 0.51 and 0.52 in the respective control groups. Inhibition EIA studies using OMP preparations or lipopolysaccharide (LPS) as free antigen indicated that proteins can play an important role in the detection of antibodies in early typhoid fever. This EIA may be useful for the diagnosis of typhoid fever since results were obtained within about five hours and in an endemic area antibodies against Salmonella typhi OMP preparations appear early in the course of the disease. PMID- 8513813 TI - Evaluation of four commercial systems for identification of medically important yeasts. AB - Four commercially available systems for identification of yeasts were evaluated using 178 clinical isolates and seven reference strains previously identified by a conventional method. After 72 h of incubation, the rate of correct identification was 86.5% with API20C Aux, 86% with Auxacolor, 68% with Mycotube and 51.1% with Candifast. When considering only the reference strains included in the manufacturers' databases, the identification rate was 90%, 91%, 87% and 61.2% respectively. Although the results at 72 h obtained with API20C Aux and Auxacolor were similar, Auxacolor led to more rapid identification of the strains, 67.9% versus 14.6% being identified at 24 h and 80.9% versus 64% being identified at 48 h. PMID- 8513814 TI - Western blot analysis of sera from Lyme borreliosis patients according to the genomic species of the Borrelia strains used as antigens. AB - Sera of 52 Lyme borreliosis patients classified according to their clinical features were analysed by Western blot using as antigens Borrelia strains belonging to three recently described genomic species. The antibody response was demonstrated to be homologous within each genospecies. Serum reactivity was studied for each of the type strains Borrelia burgdorferi sensu stricto (strain B31T), Borrelia garinii (strain 20047T) and group VS461. Seven of 15 sera (46.6%) of patients with meningoradiculitis showed preferential reactivity with Borrelia garinii (strain 20047T), all of 8 sera (100%) of patients with acrodermatitis chronica atrophicans showed preferential reactivity with group VS461 (strain VS461) and 8 of 16 sera (50%) of patients with arthritis showed preferential reactivity with Borrelia burgdorferi sensu stricto (strain B31T). The presence of a strong response to OspA and OspB proteins of Borrelia burgdorferi sensu stricto was found only in this last group of patients. These results suggest that there are clinical implications of the recently described modifications in the taxonomy of Borrelia burgdorferi. PMID- 8513815 TI - Endocarditis caused by a Leptotrichia buccalis-like bacterium in a patient with a prosthetic aortic valve. AB - The isolation of a Leptotrichia buccalis-like bacterium from the blood of a patient with endocarditis associated with a prosthetic aortic valve is reported. The organism was isolated from different blood cultures. It was similar but not completely identical to Leptotrichia buccalis. The microbiological identification was confirmed independently by three laboratories, including two reference institutions. The case and the characteristics of the microorganism are reported. PMID- 8513816 TI - Absence of Helicobacter pylori in dental plaques in Helicobacter pylori positive dyspeptic patients. AB - To test the validity of reports on detection of Helicobacter pylori in the mouth, samples were obtained simultaneously from the gastric mucosa and dental plaques for culture in 94 patients examined consecutively by endoscopy. Histological examinations and serological tests were also performed. Helicobacter pylori was not found in the mouth of any of the patients including 52 who had culture positive gastric biopsies. Thus earlier results could not be confirmed, however, other techniques such as the polymerase chain reaction might give different results. PMID- 8513817 TI - Effect of time elapsed since previous voiding on the detection of Chlamydia trachomatis antigens in urine. AB - To determine if the time elapsed since previous voiding affects the sensitivity of an enzyme immunoassay (EIA) to detect Chlamydia trachomatis in urine, 882 women and 428 men were tested for chlamydial infection in urethral specimens by isolation in cell culture (women and men) and EIA with blocking confirmation (women only). Of the 36 women (4.1%) and 38 men (8.9%) who were positive for Chlamydia trachomatis in the urethra, 55.5% (20/36) and 81.6% (31/38) respectively were positive in the first void urine (FVU) sediment by confirmed EIA. In women the sensitivity of the EIA performed on FVU was 67.8% (19/28) if the urine had been in the bladder < 3 hours and decreased to 12.5% (1/8) if longer times had elapsed (odds ratio 13.7; 95% confidence interval 1.4 to 700.0) with no obvious confounding. In men a weaker association was present (odds ratio 2.7; 95% confidence interval 0.4 to 22.3). These findings should enable investigators to optimize the analysis of urine to diagnose chlamydial infections. PMID- 8513818 TI - Serological cross-reactions between Moraxella (Branhamella) catarrhalis and other oropharyngeal bacteria. AB - Oropharyngeal bacteria belonging to different species were tested for serological cross-reactions with Moraxella catarrhalis using sera from immunized rabbits. Sera were tested using immunofluorescence, an enzyme immunoassay (EIA) and immunoblotting. On immunofluorescence, significant cross-reactions were demonstrated with beta-hemolytic streptococci group A and group G, as well as with streptococci of the viridans group. Some cross-reactions were also noted with Neisseria meningitidis. In the EIA, strong cross-reactions were demonstrated with beta-hemolytic streptococci. No cross-reactions were obtained with Streptococcus pneumoniae, Haemophilus influenzae or common oral Neisseria. The results are of importance for the interpretation of serological tests to detect infections with Moraxella catarrhalis, and for the development of methods for detection of antigens in samples from the respiratory tract. PMID- 8513819 TI - Comparative pharmacokinetics of ciprofloxacin, ofloxacin and pefloxacin in human aqueous humour. AB - Eighty-five patients undergoing cataract surgery were given for prophylaxis of intraocular infection two intravenous doses each of 200 mg, 300 mg or 400 mg ciprofloxacin (35 patients), 400 mg or 800 mg pefloxacin (30 patients), or 400 mg ofloxacin (20 patients). Ciprofloxacin levels in aqueous humour ranged from 0.02 to 0.50 microgram/ml, pefloxacin levels from 1.04 to 7.80 micrograms/ml, and ofloxacin levels from 0.44 to 2.27 micrograms/ml with ratios of aqueous humour to serum levels ranging from 3.8% to 25%, 21% to 48.1% and 44% to 88.4%, respectively. It is concluded that the quinolones studied might be suitable for surgical prophylaxis or treatment of anterior chamber infections due to Enterobacteriaceae, while ciprofloxacin at high doses is preferable for Pseudomonas aeruginosa infections. PMID- 8513820 TI - Killing kinetics of cefuroxime against Streptococcus pneumoniae in an in vitro model simulating serum concentration profiles after intramuscular administration. AB - The killing kinetics of cefuroxime against 25 Streptococcus pneumoniae isolates with penicillin MICs of < 0.1, 0.1-1.0 and 2 mg/l were studied in an in vitro model simulating the serum concentration profile in healthy adults following a single intramuscular injection of 500 mg. Cefuroxime was bactericidal against the isolates with exquisite or slightly diminished susceptibility to penicillin (-4 and -3.9 log10 cfu/ml killing, respectively) during the 6 h incubation period. In contrast, there was only a 2.8 log10 cfu/ml reduction in the initial inoculum of six of the eight isolates resistant to penicillin (MIC 2 mg/l). The two remaining penicillin-resistant isolates (cefuroxime MIC 8 mg/l) only showed a 2 log10 cfu reduction in the initial inoculum. PMID- 8513821 TI - Long-term antimicrobial treatment of severe infections using a fully implantable catheter system. PMID- 8513822 TI - Septicemia due to Capnocytophaga canimorsus after a dog bite in a cirrhotic patient. PMID- 8513823 TI - Severe neutropenia in a patient treated with imipenem/cilastatin. PMID- 8513824 TI - Isolation of Bordetella bronchiseptica from a patient with AIDS. PMID- 8513825 TI - Evaluation of Rambach agar for rapid detection of Salmonella in human feces. PMID- 8513826 TI - Survival after fungemia due to Fusarium moniliforme in a child with neuroblastoma. PMID- 8513827 TI - False positive result of Mycobacterium tuberculosis complex DNA probe hybridization with a Mycobacterium terrae isolate. PMID- 8513828 TI - Tissue thermometry during ultrasound exposure. AB - In order to quantify ultrasound therapy it is important to measure the tissue temperature during the treatment. Invasive probes induce several artifacts in ultrasound fields. The magnitude of these artifacts is probe dependent. Several different probes were evaluated for hyperthermia purposes in this study. An alternative noninvasive method to evaluate the temperature elevations and tissue damage is to use magnetic resonance imaging. The fast imaging sequences used in this study are marginally useful for monitoring hyperthermia. However, these imaging sequences can be utilized to guide and monitor ultrasound surgery. PMID- 8513829 TI - Liver cancer ablation with extracorporeal high-intensity focused ultrasound. AB - Recent animal studies have demonstrated the capacity of high-intensity focused ultrasound (HIFU) to extracorporeally ablate selective tissue targets in the liver without requiring surgical exposure of the liver or insertion of instruments into the liver. The potential value of HIFU as a noninvasive local treatment for human hepatic cancers has attracted considerable interest. This report reviews the current status of HIFU research and sets forth questions for future study. PMID- 8513830 TI - Intense focused ultrasound in medicine. Some practical guiding physical principles from sound source to focal site in tissue. PMID- 8513831 TI - High-precision thermotherapy for small lesions. AB - Many applications of ultrasonic therapy involve treatment within small tissue volumes. This situation is encountered in ocular therapy, and it requires precise lesion control and high-resolution monitoring techniques. This report describes our system for ophthalmic thermotherapy and summarizes our mathematical model describing how tissue parameters and exposure parameters influence lesion size and shape for short, ablative exposures. It also describes our clinical approaches to producing specific lesion features and presents illustrative experimental results that indicate areas for future study. PMID- 8513832 TI - Morphology of tissue destruction induced by focused ultrasound. AB - The effect of high-intensity focused ultrasound (HIFU) ablation on the morphology of prostatic, renal and testicular tissue was studied by light and electron microscopy. Specimens were obtained in 21 patients 1 h to 10 weeks after lesioning. Histological findings showed consistent coagulative necrosis with precisely defined, sharp margins to normal tissue. Lesion size and position correlated well with the assumed target zones, suggesting that HIFU permits therapeutic tissue ablation. PMID- 8513833 TI - Tissue destruction with focused ultrasound in vivo. AB - The management of some tumours presents a difficult surgical problem. Focused ultrasound surgery is a technique which provides the possibility of destroying, non-invasively, a selected volume of tissue at depth within an organ such as the liver whilst sparing overlying tissues. For the safe and effective use of this technique, it is essential to understand the way in which such a focused ultrasound surgery beam interacts with normal and malignant tissue and to study the histological response of different tissues to the ultrasonic insult. In this paper the histology of lesions in normal rat liver, as viewed by light and electron microscopy, is described. PMID- 8513834 TI - Refining the therapy of testicular seminoma. PMID- 8513835 TI - Chemotherapy of seminoma. PMID- 8513836 TI - Human yolk sac carcinoma cell lines as models for studies of yolk sac developmental functions. PMID- 8513837 TI - The epidemiology of testicular cancer. PMID- 8513838 TI - Modified retroperitoneal lymphadenectomy for testicular tumor: anatomical approach, operative technique and results. AB - Between January 1988 and June 1992, 56 patients underwent nerve-preserving retroperitoneal lymphadenectomy at the Department of Urology, University of Innsbruck. In 23 patients stage I, and in 33 patients stage II testicular tumors were found (staging according to the criteria recommended in Lugano 1979). Orchiectomy and subsequent lymphadenectomy within the boundaries described by Weissbach's group were performed for stage I tumors. In patients presenting with stage IIa or IIb tumors modified retroperitoneal lymphadenectomy within the boundaries suggested by Colleselli's group was performed. In stage IIc patients the residual tumor was resected after three cycles of polychemotherapy. If possible, nerve-sparing lymphadenectomy was performed. By adapting the operative technique to the respective tumor stage antegrade ejaculation could be preserved in 47 of these 56 patients. Semen analysis was carried out in 22 patients. The results in patients with stages I and IIa tumors were excellent, while in stages IIb and IIc patients' exocrine testicular function was considerably worse due to inductive polychemotherapy. None of the patients had a retroperitoneal recurrence. Of all 56 patients only one had a relapse in the lung (1.7%). The average follow-up period was 29 months. PMID- 8513839 TI - Nerve-sparing retroperitoneal lymphadenectomy for testis cancer. Evolution of surgical templates for low-stage disease. PMID- 8513840 TI - Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage? AB - It is uncertain as to the extent which gastrointestinal (GI) haemorrhage related to NSAIDs is due to a local, topical effect or to an action related to systemic absorption. We hypothesised that, should systemic drug concentrations be of importance, plasma levels of NSAIDs might be higher in patients who had developed GI haemorrhage, from controls who had not. Ten patients with GI haemorrhage, who had ingested piroxicam (and no other NSAID), within the preceding 64 h, at the same dosage and on no new medication for the past 14 days, had blood taken at presentation for measurement of piroxicam concentrations. Plasma piroxicam concentrations were measured in 19 community dwelling controls, matched for age +/- 8 years, gender, daily piroxicam dosage, and time from last dose as their respective index case. All had been taking piroxicam for at least 3 months, and none had experienced GI adverse effects. Median plasma piroxicam concentrations in patients at 8.27 micrograms/l, was higher than in controls at 5.06 micrograms/l. These results suggest that a systemic component, at least with piroxicam, may play a significant (though not necessarily exclusive) role in causing major gastrointestinal haemorrhage. PMID- 8513841 TI - Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose. AB - The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity. PMID- 8513842 TI - Analgesic effect and plasma concentrations of codeine and morphine after two dose levels of codeine following oral surgery. AB - A double blind randomised cross over investigation was carried out in 25 male patients undergoing two oral surgical extractions, one for each lower wisdom tooth. The two extractions were performed about 6 weeks apart and were carried out under local anaesthesia. One hour after each extraction the patients randomly received 90 or 45 mg codeine. During the following 5 h the patients rated the intensity of their pain on a visual analogue scale. Blood was simultaneously sampled and assayed for codeine and its metabolite morphine. Mean pain intensity difference was just significantly higher after 90 mg codeine compared to 45 mg. The mean plasma concentrations of codeine and morphine were significantly higher after the 90 mg dose. However, for the two dose levels of codeine there was no obvious relationship between the difference in analgesic effect and the difference in the plasma concentration of codeine or morphine. The plasma concentrations of morphine were 2-3% of those of codeine and the levels were relatively low. Local formation of morphine from codeine within the human brain should therefore be investigated. Four patients were unable to demethylate codeine to a detectable plasma concentration of morphine after 90 mg codeine. In those patients the analgesic effect during the first hours was better after 90 mg codeine than after 45 mg. This suggests some analgesic effect of codeine itself. PMID- 8513843 TI - Abnormal circulatory control in falciparum malaria: the effects of antimalarial drugs. AB - We have studied blood pressure and heart rate responses to standing in 29 previously ambulant adult Thai patients with acute uncomplicated falciparum malaria before and after treatment with quinine or mefloquine. There was significant, symptomatic, and usually profound orthostatic hypotension in 12 patients (41%) before antimalarial treatment. The median maximum fall in systolic pressure was 24 mm Hg, significantly greater than the maximum fall in diastolic pressure 16 mm Hg. Blood pressure fell in two phases: an initial transient and usually asymptomatic fall immediately on standing, and a progressive, usually symptomatic fall, worsening over several minutes without a rise in pulse rate. Orthostatic hypotension was associated with core temperature (r = 0.37, P = 0.05). Antimalarial treatment accentuated the delayed orthostatic hypotension during malaria, despite (in the case of quinine) a significant reduction in fever. Both antimalarial drugs attenuated the cardioacceleratory response to symptomatic postural hypotension; the mean reduction in heart rate at the time of lowest blood pressure was 22 beats.min-1. The electrocardiograph ratio of RR intervals at the 30th and 15th beats was reduced significantly in acute malaria, but was not affected further by the drugs. When restudied in convalescence all the patients had normal postural cardiovascular responses. Acute falciparum malaria is associated with impaired circulatory control and the tendency to postural hypotension is worsened significantly by antimalarial treatment with the quinoline antimalarials quinine and mefloquine. PMID- 8513844 TI - Influence of the application site on bioadhesion and slow-release characteristics of a bioadhesive buccal slow-release tablet of miconazole. AB - The influence of the application site on bioadhesion and release characteristics of a bioadhesive buccal slow-release tablet of miconazole has been evaluated. The adhesion time and salivary miconazole levels were measured after application of the tablet to the gingiva, the cheek and the palate in 10 healthy volunteers. The longest adhesion time noted was for the gingiva (565 min), compared to the palate and cheek with adhesion times of 210 and 243 min, respectively. Tablets adherent to the palate showed the highest initial salivary drug levels, followed by those adherent to the cheek and gingiva, respectively. The clearance rate from the oral cavity was similar when the tablet was applied to the palate and the cheek, but it was markedly decreased when applied to the gingiva. It is concluded that the gingiva is the best site for application of a bioadhesive buccal system for local therapy. A study in 8 comatose intubated patients showed that the application site had to be adapted to the state of the patients treated, as salivary miconazole concentrations comparable to those observed with the gingival tablet in healthy volunteers, were obtained after application to the cheek. PMID- 8513845 TI - Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. AB - Nine extensive metabolizers (EMs) and eight poor metabolizers (PMs) of sparteine took a single oral dose of 100 mg of desipramine HCI before and while taking paroxetine 20 mg per day. Before paroxetine, the median of the total desipramine clearance was 7 times higher in EMs than in PMs (102 and 15 l.h-1 respectively). This confirms that desipramine is extensively metabolized via the sparteine/debrisoquine oxidation polymorphism i.e. by CYP2D6. During paroxetine, the median clearances were 22 l.h-1 and 18 l.h-1 in EMs and PMs respectively. The 5-fold decrease in clearance in EMs when desipramine was co-administered with paroxetine confirms that paroxetine is a potent inhibitor of CYP2D6. The lack of effect on clearance in PMs shows that paroxetine is a selective inhibitor of CYP2D6, which is absent from the livers of PMs. Before paroxetine, the median of desipramine clearance via 2-hydroxylation was 40-times higher in EMs than in PMs (56 and 1.4 l.h-1 respectively), but during paroxetine, it was only 2-times higher (6 and 2.9 l.h-1 respectively). The increase in this clearance in PMs suggests that paroxetine is an inducer of the alternative, unidentified P450(s) which catalyze(s) the formation of 2-OH-desipramine in this phenotype. Before paroxetine, the median amounts of 2-OH-desipramine glucuronide recovered in urine were 69% and 68% of the total recovery of 2-OH-desipramine in urine in EMs and PMs respectively. During paroxetine, the corresponding values were 77% and 84%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513846 TI - Pharmacokinetics and pharmacodynamics of famotidine in patients with reflux oesophagitis. AB - The pharmacokinetics, pharmacodynamic effect and clinical efficacy of famotidine were studied in 10 patients with reflux oesophagitis Grades I and II. For the pharmacokinetic studies the patients received 20 mg famotidine i.v. The half-life of famotidine was 3.8 h, the total plasma clearance was 297 ml.min-1, and a steady state volume of distribution of 1.2 l.kg-1 was found. For pharmacodynamic assessment, intraoesophageal pH-metry was performed without and after acute treatment with famotidine 20 mg i.v. and following 3 weeks of oral famotidine 80 mg b.d. The resultant percentage total acid exposure time (pH < 4 within 24 h) were 23.9%, 19.0% and 19.2% (median), respectively (NS). At the end of 6 weeks of oral therapy, symptomatic and endoscopic improvement had occurred in 9 and 5 patients, respectively. Our study shows that the pharmacokinetics of famotidine in patients with reflux oesophagitis is comparable to that in healthy volunteers and peptic ulcer patients. The clinical response to the treatment appeared comparable to that found after other H2-receptor antagonists. PMID- 8513847 TI - The influence of steady-state ciprofloxacin on the pharmacokinetics and pharmacodynamics of a single dose of diazepam in healthy volunteers. AB - The effects of pretreatment with a seven day course of ciprofloxacin on pharmacokinetics and pharmacodynamics of an intravenous (5 mg) dose of diazepam were investigated in a group of 12 healthy volunteers in a double-blind placebo controlled crossover study. Ciprofloxacin pretreatment significantly reduced diazepam CL (without ciprofloxacin: 19.5 ml.h-1 kg-1; with ciprofloxacin: 12.3 ml.h-1 kg-1). Diazepam t1/2 was also prolonged (without ciprofloxacin: 36.7 h; with ciprofloxacin: 71.1 h), but volume of distribution was unaltered (without ciprofloxacin: 1.1 l.kg-1; with ciprofloxacin: 1.1 l.kg-1). However, no significant changes were detected in psychometric tests of digit symbol substitution, tapping rate and short memory, as well as levels of concentration, vigilance and tension measured by visual analogue scales. PMID- 8513848 TI - Determination of theophylline clearance in South African children. AB - Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability. Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l.h-1.kg-1 were 0.0949 for children aged 1-5 y; 0.0813 for children aged 5-9 y, and 0.0660 for children of 9 16 y. The values are similar to those reported in other studies. PMID- 8513849 TI - A comparison of the efficacy of cilazapril versus cilazapril plus hydrochlorothiazide in patients with mild to moderate essential hypertension. Inhibace General Practice Study Group. AB - The efficacy of cilazapril monotherapy and in combination with hydrochlorothiazide 12.5 mg was compared in a multicentre, double blind, randomised parallel group study in 87 patients with mild to moderate essential hypertension over 8 weeks. After a 2 week single blind placebo run-in period, patients received either 2.5 mg cilazapril or 2.5 mg cilazapril plus 12.5 mg hydrochlorothiazide once daily. At Week 4 the cilazapril dose was increased from 2.5 mg to 5.0 mg if the mean sitting diastolic blood pressure was greater than 90 mmHg or had not decreased by more than 10 mmHg. After 8 weeks treatment 72% of patients responded to 2.5 mg cilazapril increasing to 88% with cilazapril 5.0 mg. For cilazapril plus hydrochlorothiazide, 83% responded to 2.5 mg cilazapril increasing to 96% on 5.0 mg cilazapril. The high response rate to low dose cilazapril monotherapy and hydrochlorothiazide combination therapy has important implications for minimising the cost of therapy with ACE inhibitors. PMID- 8513850 TI - Studies on placental transfer of celiprolol. AB - The maternofetal transfer of the beta 1-selective adrenergic antagonist celiprolol has been studied in four hypertensive pregnant women. Fetal plasma concentrations were about 25-50% of the levels found on the maternal side. There was no significant difference between the plasma concentrations of the two enantiomers in the child. Therefore, in further investigations only the racemate needs to be determined. PMID- 8513851 TI - Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function. AB - Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2)%; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function. PMID- 8513852 TI - Pharmacokinetics of flosequinan in elderly patients with chronic congestive heart failure. AB - We have investigated the pharmacokinetics of the direct vasodilator flosequinan in elderly patients with congestive heart failure. Eight patients received a single dose of 50 mg, and 8 patients received once-daily treatment with 25 mg for two weeks. In the single dose study, the tmax of flosequinan was 2.5 h, Cmax was 1.17 microgram.ml-1 and t1/2 was 5.63 h. The tmax of the metabolite BTS 53554 was 20.3 h, Cmax was 1.44 microgram.ml-1 and t1/2 was 62.0 h. BTS 53554 accumulated gradually in the 14-day repeated dose study and steady-state was reached after approximately 2 weeks. Flosequinan was not found to accumulate. Adverse reactions were not observed in either the single or repeated dose study. It is advisable to consider renal function and body weight when flosequinan is to be administered to elderly patients with congestive heart failure. The initial dose should be 25 mg. PMID- 8513853 TI - Effects of diclofenac on isradipine pharmacokinetics and platelet aggregation in volunteers. AB - In this open, two-period crossover study in 18 healthy male volunteers, a single oral dose of 50 mg diclofenac was administered alone and on day 7 of multiple oral dosing of 5 mg b.i.d. isradipine to assess a possible pharmacokinetic interaction. The effect of these drugs on ex vivo platelet function was also determined. Serial blood samples were obtained over 12-hour periods on three occasions: after the single diclofenac dose; after the morning dose of isradipine on day 6 and after co-administration of both drugs on day 7 of steady-state isradipine administration. Additional samples were taken at 2 h post dose for determination of ex vivo platelet aggregation. Isradipine plasma concentrations were determined by a gas chromatographic method and diclofenac plasma concentrations by an HPLC method. The pharmacokinetic characteristics of diclofenac were unaltered during co-administration. The maximum plasma concentration of isradipine was increased 19.6% during co-administration from 5.06 to 6.05 ng.ml-1. This is not expected to be of clinical importance. Isradipine's apparent total body clearance and steady-state AUC remained unchanged. Ex vivo induced platelet aggregation was not affected by any of the treatments. PMID- 8513855 TI - Evaluation of the methodological quality of clinical trial protocols. A preliminary experience in Spain. AB - The methodological quality of 50 clinical trial protocols submitted to our hospital has been assessed by means of a check-list. The most frequent methodological deficiencies found were related to statistical analysis, selection criteria, sample size, incorrect use of placebo, homogeneity of the groups, concomitant medication, randomisation plan, monitoring of adverse events and study design. Lack of insurance for the patients and inadequacies in the investigators' brochure and case report forms were observed in a significant number of cases. The results suggest the importance of a multidisciplinary team in the elaboration of clinical trial protocols to prevent methodological errors. PMID- 8513854 TI - Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone. AB - The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg.l-1 was infused at 5 ml.min-1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg.h-1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg.l-1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513857 TI - Interpretation of chloroquine pharmacokinetic data. PMID- 8513856 TI - Tricyclic antidepressant plasma levels after augmentation with citalopram: a case study. AB - In a depressed patient, the addition of citalopram 40-60 mg per day to treatment with amitriptyline 75 mg per day had no effect on the plasma levels of amitriptyline and nortriptyline, but it led to clinical improvement without the appearance of adverse effects. This and similar findings in four other patients comedicated with citalopram and amitriptyline (2 patients), clomipramine or maprotiline suggest that citalopram differs from other selective serotonin reuptake inhibitors, such as fluvoxamine and fluoxetine, which have been shown to increase tricyclic antidepressant plasma levels. PMID- 8513858 TI - The potential role of high-dose methylprednisolone on the maturation of leukemic cells in children with acute promyelocytic leukemia (APL) PMID- 8513859 TI - Characterization of tumor cell heterogeneity of a murine leukemia cell line (L1210) in response to arabinosylcytosine: quantitation using a computerized image analysis system. AB - Cytosine arabinoside (Ara-C) is one of the most effective drugs in inducing remission in acute nonlymphocytic leukemia (ANLL) patients. However, the high recurrence rate indicates that a subpopulation of leukemic cells escapes drug effect. This cellular heterogeneity in drug response may play a major role in chemotherapeutic outcome. We have recently developed the individual colony formation assay (ICFA) to study drug effects on the kinetics of proliferation of individual cells and their progeny. Thus parameters of proliferation are calculated for individual colonies. Three categories of drug responses were defined, including immediate growth cessation, delayed growth cessation (growth stops several days after drug exposure) and growth slowdown (logarithmic growth at a reduced rate compared to control). In the experiments included in this report, murine leukemia (L1210) cells were exposed to various concentrations of Ara-C for 1, 6 or 24 hours, and their responses quantified. Regardless of the Ara C concentration or exposure time, subpopulations of cells were observed in each of the three response categories: immediate or delayed arrest or growth slowdown. As expected, the fraction of cells exhibiting immediate growth cessation generally increased with increasing drug dose and was markedly increased with longer exposure time. Delayed arrest was most prevalent at intermediate drug concentrations at all exposure times. If exposure was limited to 1 hour, at least 30% of cells continued to grow, although at a reduced rate (71% control rate after exposure to 1 mM Ara-C). This limited effect was paralleled by saturation of Ara-C triphosphate (Ara-CTP) formation. Six-hour exposure left at least 6.4% of cells growing, with an average rate of 45% of control. Under these conditions, no saturation in Ara-CTP formation was observed. Even 24-hour exposure to 5 microM Ara-C left 4.8% of colonies growing, at 42% of control rate. Thus a subpopulation of cells continued to grow even after 24-hour exposure to a relatively high concentration of Ara-C. Surviving, but slowly growing, cells may represent a previously unrecognized population that may contribute to therapeutic failure. PMID- 8513860 TI - Studies on the hyperthermic sensitivity of the murine hematopoietic stem cell compartment. I. Heat effects on clonogenic stem cells and progenitors. AB - The heat sensitivity at 42 degrees, 43 degrees and 44 degrees C of various hematopoietic subsets in murine bone marrow (MRA, CFU-S-12, CFU-S-8, CFU-GM, BFU E and CFU-E) was investigated in order to determine whether there is a relationship between heat sensitivity and the position of cells within the stem cell hierarchy. The results show that the primitive stem cell with marrow repopulating ability (MRA) is extremely heat-resistant compared with the most differentiated hematopoietic progenitor (colony-forming unit-erythroid [CFU-E]). The proliferative activity of the hematopoietic subsets was determined from the number of cells killed by hydroxyurea (HU). It is demonstrated that there is a progressive increase in the proportion of hematopoietic subset cells in S-phase with maturation. The various heat sensitivities among the different hematopoietic subsets appear to be related to their proliferative activity. This relationship may have relevance to the clinical application of hyperthermia as a purging modality. PMID- 8513861 TI - In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine 123 FACS selection. AB - Subpopulations of very primitive hematopoietic cells were isolated by fluorescence-activated cell sorter (FACS) selection of density gradient-enriched, lineage-depleted marrow cells with blast cell light scatter characteristics that bound low levels of the DNA binding dye, Hoechst 33342 (Ho) and retained differential amounts of the mitochondrial binding dye, rhodamine 123 (Rh-123). The dyes were used sequentially in a single sorting operation. The subfractions of cells that stained most weakly with both dyes were highly coenriched for long term repopulating cells (LTRC) and for in vitro high proliferative potential colony-forming cells (HPP-CFC). Furthermore, as populations of cells were progressively selected on the basis of decreasing Ho and Rh-123 fluorescence, first the CFU-S-8, then the CFU-S-12 diminished or disappeared entirely in the lowest Rh-123 fraction. In these low fluorescent populations, plating efficiency for HPP-CFC was very high when cultured in the combined presence of recombinant rat stem cell factor (rrSCF), recombinant human interleukin-1 (rhIL-1), recombinant murine interleukin-3 (rmIL-3) and recombinant human colony stimulating factor-1 (rhCSF-1), apparently reaching 100% in some instances. When 20 male donor cells from this lowest fluorescent Ho/Rh-123 fraction were injected into lethally irradiated female recipients, along with a "compromised" marrow cell population (3x previously transplanted nonsorted female bone marrow cells), the sorted male donor cells were able to completely and exclusively repopulate the myeloid and the lymphoid B and T cell compartments of the recipients for at least 10 months posttransplant. Assays of cell fractions that were relatively more Rh-123 fluorescent demonstrated the presence of cell with progressively less repopulating capacity. When descendants of transplanted low fluorescent Rh-123 selected cells, as found in 12-day spleen colonies, were assayed for the capacity to provide long-term survival in secondary recipients, they were able to do so in a high proportion of lethally irradiated recipients. However, spleen colonies derived from the mid-high fluorescence fraction were completely unable to do so. In summary, we have demonstrated with a sequential Ho/Rh-123 sorting system that a subset of HPP-CFC cofractionate with LTRC with high frequency. Using this system, the enrichment of LTRC in the lowest Rh-123 compartment of the sequentially Ho/Rh-123 selected cells appears to be the greatest demonstrated thus far. In addition, this study further supports previous ones that identify a compartment of LTRC that are largely distinct from CFU-S-12. PMID- 8513862 TI - Downregulation of M-CSF receptors by lipopolysaccharide in murine peritoneal exudate macrophages is mediated through a phospholipase C dependent pathway. AB - Murine peritoneal exudate macrophages (PEM) co-express granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) receptors, among others. Treatment of PEM with lipopolysaccharide (LPS) or tumor-promoting phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) induces a rapid but transient loss of M-CSF receptors in PEM. GM-CSF receptors are not affected by this treatment. The loss of M-CSF receptors induced by LPS can be inhibited by neomycin and compound 48/80, two potent phospholipase C (PLC) inhibitors, but not by phospholipase A2, calpain, protein kinase C (PKC) or protease inhibitors. On the other hand, the loss of M-CSF receptors induced by TPA has been prevented by PKC inhibitors but not by PLC inhibitors. PLC inhibitors also prevent LPS suppressed receptor-mediated internalization of radiolabeled recombinant human (rh) M-CSF by macrophages. Similar prevention of LPS-induced M-CSF receptor downregulation was observed in human monocytes that had been pretreated with PLC inhibitors. Our results show that 1) TPA-induced M-CSF receptor loss is strictly dependent on PKC activation; 2) PLC activation alone also leads to downregulation of M-CSF receptors; and 3) LPS-induced M-CSF receptor downregulation in PEM is mediated primarily through a PLC-dependent pathway. Our data also imply that the expression of M-CSF but not GM-CSF receptors is linked to an important, yet unknown, PLC-sensitive component(s) whose hydrolysis may lead to downregulation of M-CSF receptors. PMID- 8513863 TI - Efficacy of benzoporphyrin derivative, a photosensitizer, in selective destruction of leukemia cells using a murine tumor model. AB - The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD), and light to selectively kill leukemic cells in comparison to normal hemopoietic progenitors was investigated using a murine model, the L1210 tumor of DBA/2 mice. In vitro experiments indicated that treatment of cells with BPD and light effected a 5 to 6 log reduction of clonogenic L1210 cells under conditions which caused less than a 1 log reduction of committed myeloid progenitors, determined by colony-forming cells. This apparent therapeutic window was tested in vivo using lethally irradiated DBA/2 mice hematopoietically reconstituted with 10(6) syngeneic donor splenocytes or 5 x 10(5) bone marrow cells mixed with L1210 cells and treated with BPD and light. Reconstitution with 10(6) splenocytes resulted in successful engraftment of approximately 50% of recipients, indicating that these conditions provided limiting numbers of essential stem cells. The minimum tumor-eliciting dose was determined to be between 10(1) and 10(2) L1210 cells. Experiments in which 10(6) splenocytes were mixed with 10(6) L1210 cells and treated with BPD and light demonstrated that at 100 ng/mL of BPD and a specified light dose (5.4 joules [J]/cm2), 50% of recipients underwent successful engraftment and did not develop leukemic ascites. Animals that died under this regimen died from failure to engraft rather than from tumor burden. These results establish that this approach can effectively lower tumor burden by 4 logs with virtually no loss of essential hemopoietic progenitors. Similar results were obtained when animals received bone marrow rather than splenocytes. PMID- 8513864 TI - Thrombopoietic effects of interleukin-6 in long-term administration in mice. AB - To further investigate the thrombopoietic and adverse effects of interleukin-6 (IL-6), 2 or 10 micrograms/day of recombinant human (rh) IL-6 was administered intraperitoneally (i.p.) to mice for up to 30 days. IL-6 increased platelet count, which plateaued at a level 30 to 40% higher than control after 5 days of treatment. This cytokine also maintained the high platelet count for the duration of treatment. The count exceeded normal levels 7 days after cessation of the 30 day treatment. IL-6 also induced a remarkable increase in the size but not the frequency of megakaryocytes in bone marrow sections. The number of bone marrow colony-forming units megakaryocyte (CFU-MK) and colony-forming units granulocyte macrophage (CFU-GM) was not augmented by the administration of IL-6 in this protocol, while spleen progenitors were significantly stimulated. Small but significant increases did occur in the number of bone marrow megakaryocytes and CFU-MK, and in the proportion of CFU-MK in the DNA synthetic phase in mice treated with 10 micrograms/day of IL-6 for 30 days. Electron microscopic examination of bone marrow demonstrated that IL-6 remarkably developed the distribution of the demarcation membrane system (DMS) in mice treated for 30 days, with little change in mice treated for 5 days. The administration of 2 micrograms/day for 30 days induced a 2.2-fold increase in fibrinogen. No changes were observed in the hepatic or renal functions. Histologic and immunofluorescence studies on the kidneys revealed no significant changes compared with controls, indicating that proliferation of the glomerular mesangium did not occur. No neutralizing antibodies were detected in mice treated for 30 days. We conclude that the long-term administration of IL-6 in mice stimulates megakaryocyte maturation and platelet production with few adverse effects, and that this cytokine may be a candidate for the treatment of thrombocytopenia in humans. PMID- 8513865 TI - Interleukin-3/erythropoietin fusion proteins: in vitro effects on hematopoietic cells. AB - Erythropoietin (Epo) acts synergistically with interleukin-3 (IL-3) to induce proliferation and differentiation of erythroid progenitors. This synergy occurs at IL-3 concentrations that have little or no effect alone. To determine whether optimal expansion of erythroid cells results when they are targeted by a molecule with both IL-3 and Epo activities, fusion proteins were generated and analyzed. Expression vectors were constructed in which the coding regions of human IL-3 and Epo cDNAs were joined by either a short (2 to 3 amino acids) or long (23 amino acids) linker sequence and expressed in Chinese hamster ovary (CHO) cells. Analysis of equilibrium binding properties of the IL-3 and Epo moieties revealed that in all fusion proteins each retained the ability to bind receptor. When IL-3 was connected to Epo by a short linker, the binding affinity of the IL-3 moiety was lower. In vitro proliferative activity of each moiety was observed on cell lines responsive to IL-3, Epo or a combination of the two cytokines. Fusion of IL 3 to Epo through its amino terminus was found to result in partial loss of its function. All the fusion proteins were biologically active on human bone marrow. When IL-3 was located at the amino domain of the protein, induction of erythroid colonies was similar to that of a mixture of IL-3 and Epo. These results indicate that biological integrity of both IL-3 and Epo can be maintained when these cytokines are fused, but that enhancement of erythropoiesis over that observed with a mixture of the two cytokines cannot be achieved by their fusion alone. Other requirements such as the coexpression of the IL-3 and Epo receptors and the sharing of a receptor subunit are likely to be needed for an optimal cell response to the fusion growth factors. PMID- 8513866 TI - The effect of bilateral removal of the submandibulary salivary glands on the erythropoietic response of mice. AB - The role of the submandibular salivary gland in erythropoiesis in the male mouse (MRC TO strain) was evaluated by subjecting mice without submandibular salivary glands (SX) and control (C) sham-operated mice to a variety of stimuli intended to stress the erythropoietic system. In SX mice, after removal of the submandibular glands at age 4 weeks and observation for 8 weeks, mean hematocrit was the same as in C mice, but mean body weight was less. Bilateral removal of the submandibular glands at age 6 weeks neither affected the rate of fall and subsequent recovery of hematocrit which followed treatment with phenylhydrazine (80 mg/kg intraperitoneally [i.p.] 9 days after operation) nor altered the rate of increase in hematocrit or change in body weight which occurred during hypobaric hypoxia (0.5 atm, > 23 hours/day) for 23 days. Mean (SEM) estimates of serum immunoreactive erythropoietin after 17 hours' continuous hypobaric (0.5 atm) exposure were not significantly different between SX [186 (30) mU/mL, n = 7] and C mice [232 (17) mU/mL, n = 7]. In mice given bilateral nephrectomies at age 6 weeks--2 weeks after SX or C surgery--and then both treated with phenylhydrazine (60 mg/kg i.p.) and exposed for 17 hours to hypobaric (0.5 atm) hypoxia, mean estimates of serum immunoreactive erythropoietin were 22.6 (10.6) mU/mL and 22.3 (5.4) mU/mL in SX (n = 5) and C (n = 5) mice. Results of the study do not support the premise that the submandibular salivary glands either contribute to the erythropoietic response or are a source of extrarenal erythropoietin. PMID- 8513867 TI - Production of a functional single-chain Fv fragment from the pan-leukocyte antibody WM65 using splicing by asymmetric PCR. AB - A method of assembly of a single-chain Fv fragment is described, whereby asymmetric polymerase chain reactions (APCR) and primer extension were used to join immunoglobulin heavy and light chain variable region genes via a linker sequence. In this procedure heavy and light chain genes, together with a linker gene containing complementary sequences, were amplified by APCR to generate single-stranded products. The single stranded heavy or light chain genes were hybridized to the relevant single-stranded link product, and extended to produce double-stranded heavy-link and link-light genes. These genes then underwent another round of APCR, resulting in two single-stranded genes (heavy-link and link-light) containing extensive overlapping sequences. Hybridization and extension of these two single-stranded products allowed the formation of the complete heavy chain-link-light chain double-stranded product. Using this method, a functional single-chain Fv fragment based on the pan-leukocyte antibody WM65 was expressed and purified from E. coli. This method of immunoglobulin gene assembly by polymerase chain reaction (PCR) offers an alternative to the current methods of the genetic engineering of antibody fragments. PMID- 8513869 TI - Toward cord blood banking: density-separation and cryopreservation of cord blood progenitors. AB - It has been shown that cord blood collected at birth can be used to successfully engraft a human lymphocyte antigen (HLA)-matched sibling suffering from a malignant disease. It has been further suggested that this source of cells may be used in unrelated but HLA-compatible patients. These wide indications would imply the establishment of cord blood banks comprising 10(5) or more samples. In this report we show that it is possible to fractionate and freeze cord blood samples without major loss in granulomonocytic or erythroblastic progenitors (CFU-GM and BFU-E). Density separation should be carried out using Percoll of density 1.080. Separated samples should be frozen and thawed in the presence of DNase I. This procedure should allow the storage of approximately 10 mL samples in cryotubes containing a number of CFU-GM and BFU-E sufficient to engraft a patient weighing less than 30 kg. These data provide a rationale for establishing cord blood banks. PMID- 8513868 TI - Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7. AB - Erythroid differentiation involves the activation of a number of erythroid specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT 7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma-globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24 hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL 3).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513870 TI - Inhibitors of hematopoietic colonies are produced by certain rat fibroblastoid cell lines and are modulated by corticosteroids. AB - Both stimulatory (CSA) and inhibitory (INH) factors may contribute to hematopoietic regulation, but little is known about how their physiologic balance is maintained. Previously we have shown that antigen-defined fibroblastoid cells cultured from rat lung (ST3-/ST4+) constitutively produce INH, and those derived from bone marrow (ST3+/ST4-) respond to macrophage cytokines to release both CSA and INH into their conditioned media (CM). Here we show that this pattern was maintained in cell strains ("ST3" and "ST4") propagated from the primary cultures, and that the presence of CSA was measured in "ST4" CM if the inhibitory > 100 kd fraction was removed. Two subclones of the "ST3" line, called 2A and 9D, were selected for high or low expression of the ST3 antigen, respectively. Both produced CSA, but only 9D produced the > 100 kd inhibitor. In the CM of cells cultured in the presence of hydrocortisone, there was less INH detected but CSA was not changed. From these data, however, we cannot assess how many individual cell products might be contributing to the INH activity. These results demonstrate that the appearance of inhibitory activity in the growth media differs among fibroblast subpopulations, and that it can be modified by natural regulators such as corticosteroids. PMID- 8513871 TI - A soluble form of the human Fc receptor Fc gamma RIIA: cloning, transcript analysis and detection. AB - The Fc gamma receptors (Fc gamma R) are glycoproteins that bind the Fc region of immunoglobulin G. Human hematopoietic cells express three biochemically distinct classes of Fc gamma receptors: Fc gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16). Complementary DNA (cDNA) clones for each of the human Fc gamma receptors have been isolated from myeloid and lymphoid cells. We describe the isolation and characterization of four Fc gamma RII clones from a cDNA library obtained from a megakaryocyte-like cell line, human erythroleukemia (HEL). Three clones encode the Fc gamma RIIA transmembrane (TM) form, while one novel clone lacks the TM region but retains the cytoplasmic domain. By conducting reverse transcription coupled to polymerase chain reaction (PCR), we found transcripts coding for this unique form of receptor in RNA from platelets, HEL cells and a second megakaryocyte-like cell line, CHRF-288-11. These results were confirmed by RNase protection analysis of RNA from HEL cells. The structure of the novel cDNA suggested that it codes for a soluble form of Fc gamma RIIA. A soluble Fc gamma RII protein was detected in the conditioned medium from HEL cells but not from the Fc gamma RII-negative T cell line, Jurkat, by immunoprecipitation with the anti-Fc gamma RII monoclonal antibody (mAb), IV.3. The immunoprecipitated protein was of the expected size for a soluble Fc gamma RII lacking the TM region but retaining the cytoplasmic domain. Soluble Fc gamma RIIA may be important in modulating the interaction between immune complexes and membrane-associated Fc gamma RII. PMID- 8513872 TI - Bead transfection: rapid and efficient gene transfer into marrow stromal and other adherent mammalian cells. AB - We report a simple, rapid, efficient and cost-effective method of gene transfer into bone marrow stromal and other adherent mammalian cells. Our approach involves brief incubation of cells with glass beads in a solution containing the DNA to be transferred. We optimized the technique using COS cells (SV40 transformed kidney cell line from African green monkey) and a transient expression assay for chloramphenicol acetyl transferase (CAT). Factors affecting gene transfer include size and condition of the beads and DNA concentration, but not DNA conformation. Gene transfer efficiency, assessed in a transient expression assay for beta-galactosidase activity, was 5 and 3% in nontransformed human bone marrow stromal cells and COS cells, respectively. Long-term stable expression with the selectable marker, neomycin phosphotransferase, was demonstrated in clonogenic COS cells at a frequency of 27%. Southern analysis of resistant clones revealed the transferred DNA to be integrated in low copy number at one or two sites in the host cell genome. Comparison with electroporation and DEAE-dextran indicates that bead transfection is more efficient than the latter and less costly than either of these methods. In view of its simplicity and because the use of retroviral sequences can be avoided, bead transfection may be an attractive means of gene insertion for gene therapy. PMID- 8513873 TI - Plasmodium falciparum: role of absolute stereochemistry in the antimalarial activity of synthetic amino alcohol antimalarial agents. AB - The (+)-isomers of mefloquine and its threo analog are 1.69 to 1.95 times more active than the (-)-isomers against chloroquine-sensitive and chloroquine resistant Plasmodium falciparum in vitro. This large a differential between the activity of (+)- and (-)-isomers was not observed for other synthetic amino alcohol antimalarial agents containing a piperidine ring. The enantiomers of amino alcohol antimalarial agents in which the amine is part of an acyclic group, such as in halofantrine, displayed little, if any, differential antimalarial activity. Thus, the effect of absolute stereochemistry of the amino alcohol antimalarial agents on antimalarial activity appears to depend upon both the flexibility of the amine portion of the molecule and the structure of the aromatic portion of the molecule. PMID- 8513874 TI - Leishmania major: respiratory burst response of infected murine macrophages treated with paromomycin. AB - The effect of paromomycin sulfate (PR) on the respiratory burst response (RB) of C3H/HeJ mouse peritoneal macrophages infected with Leishmania major, LRC-L137, was studied in vitro. Giemsa staining and acridine orange staining combined with nitro blue tetrazolium (NBT) reduction reaction were used to determine parasite survival and RB response at the level of individual cells. RB response was detected in only 18% of the infected macrophages compared with 60% of the control, uninfected cells. Only 7% of the total RB-responder (NBT-positive) cells showed the presence of intracellular amastigotes. PR at 100 micrograms/ml reduced the number of the infected cells by 85% on the 4th day of cultivation. PR at the same concentration restored 50% of the RB activity of these cells. PR given alone had no effect on the RB of the uninfected macrophages. A similar effect of PR on RB activity was observed with PMA-stimulated macrophages. Both Leishmania infected and uninfected macrophages treated with PR (100 micrograms/ml) for 4 days retained 50% of their leishmanicidal activity upon reinfection due to drug accumulation within the cells. PMID- 8513875 TI - Plasmodium yoelii: splenectomy alters the antibody responses of infected mice. AB - The antibody response to Plasmodium yoelii is altered in splenectomized mice. Sera were obtained from sham-operated or splenectomized DBA/2 and C57BL/6 mice on Days 11, 18, and 24 after infection with nonlethal P. yoelii 17x and used to precipitate metabolically radiolabeled parasite antigens. Mice of both strains responded to many antigens. However, only splenectomized DBA/2 mice made strong antibody responses to antigens of approximately 110, 56, 50, 40, 35, and 20 kDa. Metabolically radiolabeled parasite extracts prepared in sham-operated and splenectomized mice appeared identical on SDS-PAGE. Thus it is unlikely that expression of new parasite antigens in splenectomized DBA/2 mice accounts for these results. Parasite-reactive IgM and IgG antibody responses were also modulated by splenectomy. Levels of IgM increased in splenectomized DBA/2 mice and decreased in C57BL/6 mice. Both mouse strains had slight to moderate increases in IgG when infected after splenectomy. The results suggest that when the spleen is present, responses to specific antigens are markedly suppressed. Alternatively, it is possible that in the absence of a spleen, antigen processing and presentation occurs in other tissues such as the lymph nodes or liver, leading to responses that are qualitatively different than those which occur when the spleen is present. PMID- 8513877 TI - Trichinella spiralis: the effect of specific antibody on muscle larvae in the small intestines of weaned rats. AB - Weaned rats were passively immunized with rat IgG2c monoclonal antibodies previously shown to protect infant rats against challenge with Trichinella spiralis. Although the antibodies did not protect rats against infection, the course of larval establishment in the intestine was altered in a way that has not been described previously. Specifically, larvae that invaded the epithelium were inhibited from migrating from intestinal tissue into saline during the standard recovery procedure. The inhibition was reversed at a time coincident with the first moult. Whole serum from infected rats had a similar effect. These results show that specific antibodies influence T. spiralis larvae in the intestinal epithelium, yet fail to effect their expulsion from adult rats. PMID- 8513876 TI - Plasmodium yoelii: cellular immune responses in splenectomized and normal mice. AB - Spleen and lymph node cells from Plasmodium yoelii 17X-infected, C57BL/6 (B6), and DBA/2 (D2) mice were cultured in vitro with parasite antigens. The ability of these cells to proliferate was quantified by uptake of [3H]thymidine and ELISA was used to measure secretion of IFN-gamma and IL-5. B6 mice are relatively susceptible to P. yoelii 17X infection compared to D2 mice. Susceptible mouse strains develop higher levels of parasitemia, become more anemic, and take longer to resolve their infections than do resistant strains. Following splenectomy, D2 mice resisted P. yoelii 17X infections as well as did sham-operated controls, but splenectomized B6 mice failed to resolve their infections and all died. Spleen cells from infected mice of either strain were activated in vitro as evidenced by their proliferation in the absence of exogenous antigen. When malaria antigen was added to these cultures, cells from resistant D2 mice responded strongly with increased proliferation, whereas cells from susceptible B6 mice responded weakly, and on Day 14 postinfection, responses were actually suppressed. Mesenteric lymph node cells from infected B6 and D2 mice did not proliferate in the presence or absence of P. yoelii 17X antigen unless the spleen was removed. Following splenectomy, mesenteric lymph node cells from D2 mice, but not B6 mice, proliferated strongly compared to cells from sham-operated controls. IFN-gamma and IL-5 production from spleen and lymph node cells was measured following in vitro stimulation with P. yoelii 17X antigen. Spleen cells from D2 mice produced levels of IFN-gamma increased over those of cells from B6 mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513878 TI - The mucosal and systemic response to phosphorylcholine in mice infected with Trichinella spiralis. AB - The presence of phosphorylcholine (PC) in Trichinella was confirmed by ELISA and Western blot experiments with the PC-specific myeloma TEPC-15. Anti-PC antibody production was detected in ELISA by cross-reaction with the PC-positive somatic polysaccharide of Aspergillus and the synthetic conjugate phosphorylcholine bovine serum albumin conjugate and by inhibition with phosphorylcholine chloride (PCCl). The kinetics of the serum and mucosal anti-PC immunoglobulin response were determined following infection of CFW mice. Anti-PC IgA was a minor fraction of the serum response. In primary infections IgG binding to Trichinella antigen was partially inhibited by PCCl incubation, but by Day 6 following challenge infections, incubation with PCCl did not reduce IgG binding. PCCl incubation also reduced serum IgM binding to Trichinella antigen following primary infections, and in contrast to IgG, a reduction occurred following challenge infection as well. Following primary and challenge infections PCCl incubations also reduced bile IgA binding to Trichinella antigen. The kinetics and subclass distribution of the anti-Trichinella PC response were equivalent to the group I response reported for synthetic PC-protein conjugates. Anti-PC IgA production indicates that class switching occurred without maturation of the response. Immunization by feeding Trichinella antigen plus cholera toxin, in contrast to infection with larvae, did not affect anti-PC antibody production following infection. Since the response was not anamnestic and the serum IgG response was not downregulated, larval infection and antigen feeding differ in the anti-PC responses they induce. The anti-PC response does not appear to be protective in Trichinella infections in mice. PMID- 8513879 TI - Leishmania mexicana: induction of metacyclogenesis by cultivation of promastigotes at acidic pH. AB - Cultivation of recently transformed Leishmania mexicana promastigotes at pH 5.5 in Schneider's Drosophila medium supplemented with 20% fetal calf serum produced a homogeneous stationary phase population morphologically similar to metacyclic forms. The cultured forms developed functional characteristics consistent with being metacyclic: they were resistant to complement-mediated lysis, possessed a discernable surface membrane coat in transmission electron micrographs, and were highly infective to peritoneal macrophages in vitro. In contrast, growth of promastigotes at pH 7.0 produced morphologically mixed populations of stationary phase promastigotes, but including a subpopulation with metacyclic-like morphology. These results provide a method for culturing pure populations of L. mexicana metacyclics and provide evidence that metacyclics are biochemically preadapted for survival at acidic pH as amastigotes in macrophage phagolysosomes. PMID- 8513880 TI - Pro-oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis. AB - Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto-oncogene bcl-2 have an increased mitochondrial membrane potential (delta psi), as have many carcinoma cells. bcl-2 protects L929 cells against apoptosis caused by pro-oxidant-induced mitochondrial Ca2+ 'cycling' and increased cytosolic Ca2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca2+ release also prevent apoptosis. It is suggested that a pro-oxidant-induced Ca2+ release from mitochondria, followed by Ca2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of delta psi stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells. PMID- 8513881 TI - Structure, function and regulation of plasma membrane H(+)-ATPase. AB - Most antigenic determinants of yeast ATPase are located within its N-terminal part. Amino acids 24-56, required for insertion at the plasma membrane, are highly accessible. The C-terminus behaves as a modulable auto-inhibitory domain in both yeast and plant ATPases. The expression of functional plant enzyme in yeast allows its mutational analysis. Plant tissues involved in active transport, such as the stomata guard cells, phloem, root epidermis and endodermis, are enriched in ATPase. One isoform is phloem-specific. The fact that auxin induces the synthesis of ATPase in corn coleoptiles provides molecular support to the 'Acid growth' theory. PMID- 8513882 TI - The membrane proteins encoded by yeast chromosome III genes. PMID- 8513883 TI - Use of reference libraries and hybridisation fingerprinting for relational genome analysis. AB - The concept of relational genome analysis by hybridisation has been developed into a working system. Various genomic and cDNA libraries have been generated and are distributed via a reference system. Analysis procedures have been tested successfully in the mapping of the entire Schizosaccharomyces pombe genome. In another test-case for their refinement, analyses on the Drosophila genome are well under way. Human and mouse libraries are being studied on all levels, from generating YAC maps to partially sequencing representative cDNA libraries. The automation of the involved processes and the development of improved image detection and analysis are well advanced. PMID- 8513884 TI - X-linked Kallmann syndrome. A neuronal targeting defect in the olfactory system? AB - Kallmann syndrome is a human genetic disorder characterized by the association of hypogonadism with the inability to smell, and is due to defects in the olfactory system development (i.e. incomplete migration of olfactory axons and of gonadotropin-releasing hormone producing neurons from the olfactory epithelium to the forebrain; aplasia or hypoplasia of olfactory bulbs and tracts). The human X linked Kallmann syndrome gene and its chicken homologue have been cloned. Their protein products contain fibronectin type III repeats and a 'four-disulfide-core' domain also found in molecules that are involved in neural development. Consistent with the human phenotype, the chicken Kallmann gene is expressed in the developing olfactory bulb. At present the molecular and cellular mechanism of action of the Kallmann syndrome gene product is unknown. Based on expression studies and the characteristics domains of the predicted protein, it is hypothesized that the protein may be involved in targeting olfactory axons to the bulb. Alternatively, the Kallmann protein could be an extracellular matrix component required for the proper formation of the multilayered structure of the olfactory bulb. PMID- 8513885 TI - Why do genes have introns? PMID- 8513886 TI - Towards a molecular resolution of the ordinal phylogeny of the eutherian mammals. AB - Reconstructing the evolutionary relationships among the orders of eutherian mammals entails the identification of a single true phylogenetic tree out of approximately 10(19) possible ones. The morphological and paleontological legacy to the field consists of numerous contradictory trees that are mostly devoid of binary resolution. With the introduction of molecular methodologies, several superordinal relationships have been identified, and in several instances a complete taxonomic revision was indicated. In this review, I present a summary of the phylogenetic affinities of the eutherian orders as revealed by molecular studies, and outline the differences between the molecular phylogenetic schemes and the phylogenetic trees produced through the use of morphological data. Questions of monophyly or paraphyly of the eutherian orders are also discussed. It is estimated that all but 10(9) of the 10(19) possible phylogenetic trees have been ruled out by molecular analysis, and that DNA and protein sequences with their potential to supply millions of phylogenetically useful characters will resolve the phylogeny of the orders of mammals into a consistently bifurcating tree in the not-so-distant future. PMID- 8513887 TI - Towards protein folding by global energy optimization. AB - Different components of the theoretical protein folding problem are evaluated critically. It is argued that: (i) as a rule, small- and medium-sized proteins are in the free energy minimum; (ii) long-living metastable states may either appear occasionally with growing protein size, or be selected by evolution for a specific function; (iii) functions discriminating against incorrect folds would fail if they were used directly in the global optimization, unless they approximate the true free energy accurately; (iv) surface and electrostatic free energies should be treated separately; (v) conformational entropy (of side chains in particular) should be taken into account; (vi) Monte Carlo procedures considering all free energy terms and combining global knowledge-based random moves with local optimization have the largest potential for success. PMID- 8513888 TI - Why are the same protein folds used to perform different functions? AB - A small number of folding patterns describe in outline most of the known protein globules, the same folds being found in non-homologous proteins with different functions. We show that the 'popular' folding patterns are those which, due to some thermodynamic advantages of their structure, can be stabilized by a lot of random sequences. In contrast, the folds which are rarely or never observed in natural globular proteins can be stabilized only by a tiny number of random sequences. The advantageous folds are few, they tolerate various primary structures, and therefore they can and ought to perform different functions. A connection between the inherent 'weak points' of protein folding patterns and positions of active sites are discussed. PMID- 8513889 TI - Predicting the conformation of proteins. Man versus machine. AB - Two types of approaches for predicting the conformation of proteins from sequence data have lately received attention: 'black box' tools that generate fully automated predictions of secondary structure from a set of homologous protein sequences, and methods involving the expertise of a human biochemist who is assisted, but not replaced, by computer tools. A friendly controversy has emerged as to which approach offers a brighter future. In fact, both are necessary. Nevertheless, a snapshot of the controversy at this instant offers much insight into the structure prediction problem itself. PMID- 8513890 TI - Location of tolerated insertions/deletions in the structure of the maltose binding protein. AB - In a previous study [(1987) J. Mol. Biol. 194, 663-673], we isolated ten insertion/deletion mutants (indels) of the maltose binding protein for which the maltose binding constant was only a little or not at all affected. In this paper, we have localized these mutations in the recently solved three-dimensional structure. Contrary to the general expectation, most of the insertion/deletion modifications occurred within elements of secondary structure. An analysis of the inserted residues for three indels found within alpha helices allowed an interpretation regarding protein structure accommodation to such modifications. PMID- 8513891 TI - Engineering type 1 copper sites in proteins. AB - The use of site-directed mutagenesis methods has revolutionalized the study of the so-called type 1 and type 2 copper sites in proteins. In particular our understanding of the relation between the structure, and the mechanistic and spectroscopic features of these sites is benefitting from the application of these techniques. Recent progress in the field is reviewed with emphasis on the study of type 1 sites. Topics covered comprise the characteristics of the natural type 1 and type 2 sites, the genetics of blue copper proteins, the modification of Cu sites, the spectroscopy of natural and engineered type 1 and type 2 sites, the effect of mutations on midpoint potentials and the mechanism of electron transfer as carried out by the blue copper proteins. PMID- 8513892 TI - The sixth Datta Lecture. Protein folding and stability: the pathway of folding of barnase. AB - The pathway of folding of a protein will be completely solved when the structures and energetics of the initial unfolded states, all folding intermediates, all transition states and the final folded state, have been determined. The ultimate goal is to analyse, at the detail of individual residues, the non-covalent interactions that are primarily responsible for dictating secondary and tertiary structure. Until recently, the tools for tackling such a daunting task were quite inadequate, but recent developments in NMR and protein engineering have made it possible to determine crucial features in the folding process. It now seems feasible that sufficient experimental detail will be obtained to provide general principles that govern protein folding and provide the basis for its rigorous theoretical analysis. This lecture will outline the progress and prospects in attainment of the goals as applied to the small ribonuclease, barnase. PMID- 8513893 TI - A new perspective on muscle contraction. AB - Recent experimental findings suggest that the myosin cross-bridge theory may no longer be adequate to account for certain basic facts concerning muscle contraction. A newly-proposed mechanism based on length changes in actin filaments might be the basis for a simpler explanation for how the free energy of ATP hydrolysis can be transduced into work by muscle fibers. PMID- 8513894 TI - The humoral antibacterial response of Drosophila. AB - Drosophila, like other insects, responds to the injection of bacteria by the rapid and transient synthesis of a battery of potent antibacterial peptides. Only a few of these peptides have been fully characterized to date. We review our recent data on the control of the expression of a gene encoding one of the induced peptides, i.e. diptericin. Our data highlight the role of proximal cis regulatory motifs similar to regulatory elements binding NF-kappa B and NF-IL6 in promoters of some immune genes of mammals. We argue that the Drosophila host defense is homologous to the mammalian acute phase response. PMID- 8513895 TI - Protein translocation across the thylakoid membrane--a tale of two mechanisms. AB - In vitro reconstitution assays have been used in recent years to probe the mechanisms by which a variety of cytosolically synthesised proteins are transported across the thylakoid membrane within higher plant chloroplasts. The emerging data suggest that two distinct mechanisms operate. Translocation of a subset of lumenal proteins, namely the 23 kDa and 16 kDa proteins of the oxygen evolving complex, and of the CFo2 protein (an integral membrane protein), requires only the presence of the thylakoidal delta pH. In contrast, two other lumenal proteins, the 33 kDa oxygen-evolving complex protein and plastocyanin, require also the presence of ATP and at least one stromal factor for efficient transport into isolated thylakoids to take place. PMID- 8513896 TI - NADH-cytochrome b5 reductase and cytochrome b5 isoforms as models for the study of post-translational targeting to the endoplasmic reticulum. AB - Cytochrome b5 and NADH-cytochrome b5 reductase are integral membrane proteins with cytosolic active domains and short membrane anchors, which are inserted post translationally into their target membranes. Both are produced as different isoforms, with different localizations, in mammalian cells. In the rat, the reductase gene generates two transcripts by an alternative promoter mechanism: a ubiquitous mRNA coding for the myristylated membrane-bound form, and an erythroid mRNA which generates both the soluble form and a nonmyristylated membrane-binding form. The available evidence indicates that the ubiquitous myristylated form binds to the cytosolic face of both outer mitochondrial membranes and ER. In contrast, two genes code for two homologous forms of cytochrome b5, one of which is found on outer mitochondrial membranes, the other on the ER. The gene specifying the ER form probably also generates an erythroid-specific mRNA by alternative splicing, which codes for soluble cytochrome b5. Possible molecular mechanisms responsible for the observed localizations of these different enzyme isoforms are discussed. PMID- 8513897 TI - The nuclear pore complex. AB - Over the past years, significant progress has been made both in the analysis of the structural and molecular organization of the nuclear pore complex (NPC) and the mechanism of nuclear transport. In this minireview, I will focus on some of the recent developments in this field. Structural studies employing high resolution EM have revealed a detailed view of the three-dimensional organization of the NPC. In addition, an isolation procedure which yields highly enriched NPCs from yeast has given insight into the molecular complexity of the NPC organization. By biochemical, immunological and genetic approaches, a series of novel pore proteins were identified. Exploiting yeast as a genetic system, several mutants defective in nuclear import of proteins and export of RNA were selected. By in vitro nuclear transport assays, soluble cytoplasmic factors including NLS (nuclear localization sequence) binding proteins and heat shock proteins required for nuclear accumulation were found. The aim of the future research must be to put these various components of the NPC and nuclear transport machinery in a topological and functional context. PMID- 8513898 TI - alpha-Latrotoxin receptor. Implications in nerve terminal function. AB - alpha-Latrotoxin is a potent stimulator of neurotransmitter release from nerve terminals. High affinity membrane alpha-latrotoxin receptor was purified in an active binding form. It is a membrane glycoprotein (M(r) 160,000-220,000) which may be complexed to a smaller polypeptide (M(r) 29,000). The structure of the receptor protein suggests that it may be a synapse-specific cell recognition molecule. Intracellularly, the alpha-latrotoxin receptor interacts with synaptotagmin, a calcium- and phospholipid-binding protein specifically localized in the synaptic vesicle membrane. This interaction may be important for targeting of synaptic vesicles to presynaptic release sites. PMID- 8513899 TI - Endovascular stenting of abdominal aortic aneurysms. PMID- 8513900 TI - Endovascular treatment of abdominal aortic occlusive disease: the impact of stents and intravascular ultrasound imaging. AB - Distal abdominal aortic occlusive disease has been conventionally treated with endarterectomy or bypass grafting. However, today's expanding spectrum of intraluminal devices and techniques may well replace classical surgery in this arterial region in all but a few instances. Since January 1990, we have investigated the potential for such endovascular therapies as thrombolysis, balloon dilation and intravascular stenting in 29 symptomatic patients with a variety of distal abdominal aortic pathologies. The prudent application of these intraluminal therapies hinges on accurate intra-arterial assessment. Arteriographic data are notably inadequate for most endovascular procedures; however, intravascular ultrasound imaging (IVUS) is a newer diagnostic tool that works particularly well in the aortoiliac region where angioscopy is more difficult to utilize for assessment. Using IVUS as a complement to arteriography, we were able to assess the need for 43 Palmaz stents in these cases of distal abdominal aortic pathologies; 23 additional iliac stents were deemed necessary. Moreover, IVUS was the only tool available to confirm adequate stent deployment. Given the apparent long-term success of stents in large-bore arteries, abdominal aortic stenting may ensure proximal inflow to distal vessels, saving many patients from an intra-abdominal operation. The specific intraluminal and transmural data offered by IVUS facilitates stent application and documents adequate deployment, two vitally important elements in the percutaneous treatment of abdominal aortic occlusive disease. PMID- 8513901 TI - Stenosis development at the distal anastomosis of prosthetic bypasses for aortoiliac occlusive disease. Incidence and accuracy of colour flow duplex in the diagnosis. AB - When bypasses for aortoiliac occlusive disease fail they often do so because of a stenosis at the distal anastomosis. To assess the incidence of stenotic lesions and to establish the diagnostic reliability of colour-flow Duplex scanning, we investigated 103 aortoiliac and aortofemoral bypasses using intravenous (i.v.) digital subtraction angiography (DSA) as the reference method. Stenotic lesions at or just beyond the distal anastomosis were identified by i.v. DSA in 30 patients. The stenosis had a 30-49% diameter reduction (DR) in 10, 50-79% DR in 17 and 80-99% DR in three patients. The incidence of stenoses identified within the first 3 years following the operation was 33%, in the period of 3-6 years 20%, in the period of 6-9 years 32% and for bypasses longer than 9 years after the operation 50%. Colour-flow imaging had a 89% sensitivity in identifying the presence and location of distal anastomotic stenosis and a 95% specificity of ruling out significant lesions. A threshold value of 0.65 of the index between the peak systolic velocity (PSV) at a normal vascular segment and the maximum PSV at the side of stenosis demonstrated lesions with a sensitivity of 86% and a specificity of 90%. Prophylactic repair of a high grade stenosis (> 70% DR) was performed in only two patients. Colour-flow Duplex is accurate in identifying distal anastomotic stenoses. Although the precise incidence of these lesions can be determined only by a prospective surveillance study, available data suggests a low yield of cases requiring prophylactic repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513902 TI - Carotid bifurcation imaging: magnetic resonance angiography compared to conventional angiography and Doppler ultrasound. AB - PURPOSE: to evaluate the clinical usefulness of the two dimensional "Time of Flight" (2D TOF) Magnetic Resonance Angiography technique (MRA) in imaging the carotid bifurcation as compared to conventional angiography and pulsed and colour Doppler ultrasound. METHODS: in 19 patients with possible cerebrovascular disease and eight volunteers, contrast angiography was compared with MRA in 21 carotid bifurcations and with Doppler ultrasound in 23 bifurcations by two independent observers. In 19 bifurcations, all three techniques were available for comparison. Internal carotid arteries were graded normal/minimal disease, mild, moderate or severe stenosis, or occluded. RESULTS: overall agreement between contrast angiography and MRA existed in 62% for one observer and 76% for the other. When MRA and Doppler agreed, agreement between these two investigations and contrast angiography existed in 77-81%. The major problem with MRA was overestimation of moderately stenosed vessels; 50% of the vessels with a moderate stenosis on contrast angiography were judged severely stenosed on MRA. An occlusion was never mistaken for a stenosis by MRA. Evaluating the separate slices, acquired in the 2D TOF MRA investigation, appeared to be essential to avoid this mistake. CONCLUSION: at present 2D TOF MRA is not clinically useful for diagnosing the degree of carotid artery stenosis. MRA has a clear tendency to overestimate the degree of stenosis especially moderately severe stenoses. To date, there are no objective methods to correct for this mistake. Technical improvements may make MRA a better diagnostic tool in the future. PMID- 8513903 TI - Post-carotid endarterectomy hyperperfusion syndrome: preliminary observations for identifying at risk patients by transcranial Doppler sonography and the acetazolamide test. AB - Patients at risk of hyperperfusion syndrome after carotid endarterectomy are often severely hypertensive and have a high grade internal carotid artery stenosis with disordered autoregulation due to a loss of reserve capacity (RC). Cerebral RC can be studied by sophisticated and expensive technical devices (SPECT, PET). Recently it has been demonstrated that the transcranial Doppler (TCD) and acetazolamide provocation test can be used to assess RC. From September 1991 to January 1992, 36 patients were studied by the TCD and acetazolamide test prior to carotid endarterectomy to identify patients at high risk of the hyperperfusion syndrome. Preoperatively, the patients were studied by TCD at rest and after vasolidation with acetazolamide 1 g intravenously (i.v.). Mean blood flow velocity on the middle cerebral artery (MCAv) was recorded for the following 20 min at 5 min intervals. MCAv at rest was 49 +/- 17 cm/s. After acetzaolamide infusion in 33 patients (92%), the mean MCAv was 62 +/- 19 cm/s with an increase of 19 +/- 13 cm/s (normal RC). In three patients (8%), the mean MCAv was 43 +/- 22 cm/s with a decrease of -6 +/- 3 cm/s with respect to base values (reduction of RC). (t = 3.30; p = 0.0022). All these patients were hypertensive (BP > 180/100 mmHg) and had a carotid artery stenosis > 90%. Postoperatively, the three patients with reduction of RC complained of homolateral headache. TCD showed a mean MCAv of 67 +/- 17 cm/s, an increase compared to the preoperative rest values of 17 +/- 8 cm/s, the 33 patients with normal RC showed a mean change in MCAv -2 +/- 12 cm/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513904 TI - The adhesion of labelled neutrophils on synthetic vascular grafts. An experimental porcine study. AB - The adhesion of neutrophils onto different vascular grafts was studied in vivo in a pig model. In acute experiments autologous 111In-labelled neutrophils were reinfused after end-to-side implantation of 5 cm, 6 mm internal diameter grafts. The dynamic deposition on each graft was determined for 300 min in vivo. Static measurements in vitro concluded the study. The adhesion was greater in Dacron and collagen coated Dacron grafts compared to expanded polytetrafluoroethylene (ePTFE) and to Dacron grafts coated with a polymer. The segmental activity along all the grafts increased towards the distal anastomosis. The results suggest different inflammatory response to various graft materials. PMID- 8513905 TI - Axillodistal bypass on critical limb ischaemia. AB - The axillodistal extra anatomic bypass is not an operation commonly performed and the only reason for performing it is to attempt limb salvage for a reasonable period of time or until death in patients with critical ischaemia. During the period 1983-1991 we performed 67 such bypasses where no other form of reconstructive arterial surgery was feasible. There were 27 axillopopliteal (15 below and 12 above the knee), five crossover, seven bilateral, 11 axillotibial and 17 jump (sequential bypasses). The first 34 procedures (1983-1987, early period) had a 5-year cumulative secondary graft patency of 20%, which increased to 33% for the 33 bypasses performed during the second period (1987-1991). The primary graft patency of the 67 bypasses was 13%. Our clinical results show that even in these patients with diffuse occlusive arterial lesions, limb salvage is possible in a reasonable number even when axillodistal bypass is used. Improvements in the technique, better selection of patients, the performance of jump grafts and the aggressive treatment of early and late graft occlusions have led to much better results being achieved. PMID- 8513906 TI - The influence of collagen and albumen presealants on knitted Dacron grafts. AB - Dacron arterial grafts may be sealed with collagen or albumen to avoid preclotting. The influence on graft thrombogenicity and maturation was studied in 36 patients undergoing elective arterial bypass surgery for aortoiliac disease randomised to (i) collagen impregnated (Meadox Hemashield), (ii) albumen coated (USCI) or (iii) standard knitted Dacron (Meadox Microvel, UCSI Vasculour II) preclotted with the patient's own blood. Five days and 2 months postoperatively, autologous 111indium-labelled platelet deposition was measured as the daily increase in the ratio of graft to blood radioactivity and expressed as the Thrombogenicity Index (TI) (units, 10(-3). Duplex Doppler examination was used to detect thrombus, neointima or perigraft fluid. TI (median and interquartile range) was similar in the grafts at 5 days at 2.12 (-0.026-3.67) for preclotted Dacron, 2.72 (1.69-7.15) for collagen impregnated and 2.7 (2.13-8.56) for albumen coated Dacron, and was not significantly different at 2 months at 2.66 (2.07 5.18) (n = 9), 4.22 (1.3-7.02) (n = 8) and 2.89 (1.03-16.5) (n = 7), respectively. Duplex Doppler demonstrated perigraft fluid at the proximal anastomosis of an occluded albumen coated graft but no further abnormalities were detected. On these data sealing of knitted Dacron with collagen or albumen does not influence early graft thrombogenicity or maturation. PMID- 8513907 TI - Bacterial adherence to synthetic vascular prostheses and influence of human plasma. An in vitro study. AB - The in vitro adherence of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli to five commercially available prosthetic vascular graft materials was compared. The influence of precoating the segments with human plasma for 2 h was also studied. S35-methionine was used to radiolabel bacteria. The segments were exposed to bacterial suspensions of approximately 10(7) CFU/ml at 37 degrees C for 0.5-18h. Following repeated washing in phosphate buffered saline (PBS), radioactivity associated with the segments was measured. The adherence of the three clinically relevant bacterial species was higher to untreated Dacron than to gelatin or collagen impregnated/coated Dacron or to PTFE. Furthermore, precoating of grafts with human plasma reduced bacterial adherence to woven Dacron, had a little effect on gelatin coated Dacron, but increased the adherence to collagen treated Dacron and, in particular, to PTFE. PMID- 8513908 TI - A haemodynamic comparison of intrathecal morphine and sufentanil supplemented with general anaesthesia for abdominal aortic surgery. AB - The haemodynamic changes associated with intrathecal morphine (IM) compared to intrathecal sufentanil (IS) as a supplement to general anaesthesia for elective bypass grafting in patients with aortoiliac occlusive disease were studied. Thirty-six, ASA Grade 2, patients randomly received morphine hydrochloride (0.1%) 50 micrograms kg-1 (n = 18) or undiluted sufentanil, 150 micrograms (n = 18) intrathecally at T12-L1, combined with light general anaesthesia. Haemodynamics were measured before and after endotracheal intubation, abdominal incision, aortic cross-clamping and the first revascularisation. The major differences were recorded after abdominal incision. Heart rate, systemic blood pressure and coronary perfusion pressure were significantly lower in the IS group. The probable cause was greater systemic absorption of sufentanil and its faster binding to the specific opiate receptors, resulting in a more efficacious supraspinal and spinal blockade during the first surgical period. However, both opioids provided adequate analgesia during the whole surgical procedure. PMID- 8513909 TI - Selection of patients with critical limb ischaemia for femorodistal vein bypass. AB - The merits of an aggressive policy of distal reconstruction have been questioned by some observers. To determine the factors affecting graft patency and mortality, we analysed 78 consecutive infragenicular femorodistal vein grafts performed in 72 patients with critical limb ischaemia. The primary, primary assisted and secondary graft patency rates at 36 months were 29, 57 and 64%, respectively. The limb salvage and patient survival rates at 36 months were 67 and 74%, respectively. Univariate analysis (log-rank test) was performed to identify factors affecting graft patency, limb salvage and mortality at 1 month (perioperative) and 1 year. Independent variables of age, sex, diabetes, presentation, level of anastomosis and vein technique (reversed or in situ) did not affect graft patency. The ankle systolic pressure did not predict graft patency but was an independent variable affecting mortality (p = 0.047), as did diabetes (p = 0.019). These results show that excellent limb salvage can be successfully achieved in severely ischaemic patients by adopting an aggressive approach to femorodistal bypass, and that age, gender and poor medical condition are not contraindications to femorodistal bypass. The difference between the primary and primary assisted patency rates in this series is dramatic and reflects the impact of a vein graft surveillance programme in preventing graft occlusion. PMID- 8513910 TI - Management of primary aortic graft infection by extra-anatomic bypass reconstruction. AB - In this retrospective study, 21 patients requiring treatment for primary infection of an aortic prosthesis between 1981 and 1991 were identified from a prospective register. Ten of the 21 patients had had additional peripheral reconstructive vascular surgery before the diagnosis of aortic graft infection. The median interval between aortic graft insertion and diagnosis of graft infection was 16 months (range 1-84). Infected grafts were removed and an extra anatomic bypass constructed in all patients. All but three patients had axillodistal reconstruction. Six patients had simultaneous operations, whilst the other 15 patients had a staged procedure with extra-anatomic reconstruction preceding graft removal. Two patients died before discharge from the hospital (9.5%). No patient required extremity amputation in the perioperative period. By life-table analysis patient survival (including perioperative deaths) was 80% at 1 year, 55% at 3 years and 40% at 5 years. Primary patency was 62% at 1 year, 51% at 3 years and 40% at 5 years. Limb salvage rate was 89% at 1 year, 63% at 3 years and 63% at 5 years. The median length of follow-up was 24 months. Extra anatomic reconstruction in patients with aortic graft infection can be performed with low perioperative mortality. Limb salvage rates following extra-anatomic reconstruction are determined not only by the mode of reconstruction, but also by the primary disease. PMID- 8513911 TI - Immediate effects of carotid clamp release on middle cerebral artery blood flow velocity during carotid endarterectomy. AB - Transcranial Doppler ultrasound was employed in 44 patients undergoing carotid endarterectomy in order to identify factors associated with the greatest increases in middle cerebral artery blood flow velocity (MCAV) immediately after carotid clamp release and restoration of flow. Previous reports have suggested that such increases might reflect post-ischemic hyperaemia. Overall, the median increase in MCAV on restoration of flow [58 cm/s (95% Cl 44-68)] was greater than the median decrease in MCAV after initial carotid clamping [36 cm/s (95% Cl 26 43), p < 0.0001]. However, the immediate increase in MCAV tended to be transient and, in one patient, may have represented a hyperaemic response to a haemodynamically induced intraoperative neurological deficit. There was no association between the magnitude of MCAV increase and clinical presentation, degree of carotid stenosis, computed tomography scan findings, type of anaesthesia, nor the presence or absence of impaired cerebral vascular reserve, nor the occurrence of intraoperative air embolisation. The greatest increases in MCAV on clamp release were observed in patients with the greatest decreases in MCAV at clamping and those with the lowest internal carotid artery stump pressures. The most likely explanation for the findings is that they represent a transient hyperaemic response to carotid occlusion. It remains unclear whether this phenomenon is mediated by some degree of ischaemic injury or simply by the effect of a sudden surge of blood through low resistance arterioles that have dilated in order to maintain the collateral circulation during carotid clamping. PMID- 8513912 TI - Contralateral stenosis and stump pressures: parameters to identify the high risk patient undergoing carotid endarterectomy under local anaesthesia. AB - Carotid endarterectomy (CEA) under local anaesthesia (LA) enables the assessment of the two parameters of stump pressure and contralateral stenosis as predictors of neurological complications both intra- and postoperatively. Over a 7 year period, 175 carotid endarterectomies were performed under LA and of these, stump pressure measurements and angiographic findings were recorded on 99 patients. There were no deaths, two patients (2.0%) suffered a perioperative stroke (CVA) and one (1.0%) a transient ischaemic attack (TIA). An additional eight patients "obtunded" while the internal carotid artery was clamped, with complete resolution upon revascularisation in all but one patient who recovered fully within 24 h. Patients with contralateral occlusion or > or = 80% stenosis were more likely to develop complications (6/25 vs. 5/74 p < 0.03) and stump pressures were significantly lower in patients suffering an event (34.36 +/- 23.15 vs. 55.57 +/- 27.58, p < 0.02). By combining contralateral stenosis (> or = 80%) and stump pressure (< or = 35 mmHg), a "high risk" group of 42 patients in whom eight of the 11 events occurred, were identified. Contralateral stenosis and low stump pressures can be used in combination to identify high risk patients likely to develop neurological complications during or following CEA. PMID- 8513913 TI - Acute thrombosis of the non-aneurysmal abdominal aorta. AB - Fourteen patients admitted over a 9 year period with acute thrombotic occlusion of the non-aneurysmal abdominal aorta have been reviewed. Twelve patients underwent aortic bifurcation graft reconstruction, one thromboendarterectomy alone, and one a re-entry operation for dissection. Two patients (14%) died in the perioperative period. The mean postoperative survival of the remaining patients is to date 55 (range 4-93) months with a mean follow-up period of 69 (range 18-100) months. The results indicate these patients should be treated aggressively by early reconstructive surgery in the expectation that the majority will survive their operation and gain a useful extension to their lives. PMID- 8513914 TI - Immediate shear stress resistance of endothelial cell monolayers seeded in vitro on fibrin glue-coated ePTFE prostheses. AB - The shear stress resistance of endothelial cells (EC) previously seeded onto ePTFE grafts was assessed by morphometric determination of the number of cells per cm2 of graft surface before and after exposure of 6 h of arterial blood flow interposed in the canine femoral artery. Autologous venous endothelial cells (AVEC) were harvested from the extrajugular veins of five dogs. The AVEC were cultured in vitro and seeded at a density of 150 x 10(3) cells per cm2 onto 4 mm ID ePTFE grafts precoated with fibrin glue and human fibronectin. Subsequently, the AVEC monolayers on the grafts were cultured for 8 days using a perfusion system and then implanted end-to-end in the femoral artery. All grafts remained patent (5/5). Scanning electron microscopy demonstrated complete, thrombus-free monolayers of AVEC after 6 h of arterial blood flow. The cell densities were 124 +/- 14 and 129 +/- 7 x 10(3) cells per cm2 respectively before and after implantation. It is concluded that in vitro lining of 4 mm ePTFE vascular prostheses is feasible and results in EC monolayers on the graft surface which are shear stress resistant and athrombogenic. PMID- 8513915 TI - Femorocrural grafting and regrafting: does polytetrafluoroethylene have a role? AB - Between 1980 and 1988, 263 patients received 307 femorocrural bypass grafts. 180 were primary infrainguinal grafts, 106 secondary, 18 tertiary and three quaternary. Rest pain or tissue loss was the indication in 96% of cases. Outflow vessels were the tibioperoneal trunk (n = 34), posterior tibial artery (n = 115), peroneal artery (n = 89) and anterior tibial artery (n = 69). 88 primary vein grafts were completed. 201 polytetrafluoroethylene (PTFE) grafts were inserted (92 primary and 109 subsequent reconstructions). There were no direct PTFE to crural vessel anastomoses. A Miller cuff was used in the majority (n = 175). The three year primary patency for primary vein grafts (36%) was similar to primary PTFE grafts (29%), but significantly higher than subsequent PTFE grafts (20%) (p = 0.03). Three year foot salvage for primary vein grafts (65%) was similar to primary PTFE (64%), but significantly better than subsequent PTFE (42%) (p = 0.02). The results support both redo femorocrural grafting for critical ischaemia, as judged by foot salvage rates, and the use of PTFE with a distal vein cuff in primary and subsequent femorocrural reconstruction if autologous vein is not available. PMID- 8513916 TI - Jugular vein transposition for the treatment of subclavian vein obstruction in haemodialysis patients. PMID- 8513918 TI - Popliteal entrapment syndrome: misdiagnosed as a compartment syndrome. AB - We report a case of popliteal artery entrapment syndrome which was originally diagnosed as a chronic compartment syndrome. The relative occurrence of the two conditions and their very similar symptoms explain the misdiagnosis. The diagnostic methods and surgical treatment for both conditions are discussed and suggestions are made as to possible non-invasive screening methods. PMID- 8513917 TI - Stenting for vein graft stenosis. PMID- 8513919 TI - Avoiding blow-out of the aortic stump by reinforcement with fibrin glue. A report of two cases. AB - Generally vascular surgeons agree that the most rational way to treat a patient with an infected aortic graft or aortoenteric fistula is excision of the graft, closure of the aortic stump and construction of an axillobifemoral bypass. Due to the feared complication of blow-out of the aortic stump, other solutions have been proposed, such as in-situ reconstruction with homologous saphenous veins or even with a synthetic graft, provided the perigraft fluid is non-purulent. Since this alternative is not always feasible, various methods to reinforce the closure of the aortic stump have been proposed. The present report describes two cases, where fibrin glue (Tisseel) was successfully used to reinforce the suture row of the aortic stump. PMID- 8513920 TI - A pseudo-aneurysm of the internal mammary artery: a very rare complication of subclavian vein puncture. AB - An extensive number of complications after insertion of a subclavian catheter is described in the literature. In this case report a patient with a pseudo-aneurysm of the internal mammary artery after insertion of a subclavian catheter is described. If one finds a shadow on the X-ray of the chest after insertion of a subclavian catheter, the possibility of a pseudo-aneurysm should be considered first. PMID- 8513921 TI - "Asymptomatic" ruptured aneurysm: a report of two cases of aortocaval fistula presenting with cardiac failure. AB - Two cases of aortocaval fistula are described in patients with an otherwise asymptomatic abdominal aortic aneurysm. Both presented because of cardiac symptoms, one with chest pain and acute heart failure and electrocardiogram signs of acute coronary ischaemia, the other with a long history of chronic cardiac failure resistant to therapy. In the first case the fistula was proven by means of a CAT scan. Positive proof of a fistula or leakage is important because asymptomatic aneurysms should not be operated on in cardiac compromised patients. On the other hand, if an aortocaval fistula is present, operation is necessary to prevent fatal cardiac failure. PMID- 8513922 TI - Retroperitoneal haemorrhage: a dangerous complication of common femoral arterial puncture. AB - Three cases of retroperitoneal haemorrhage resulting from femoral artery catheterizations are reported. The blood tracked up the femoral sheath and was not accompanied by local clinical signs. Two of the patients died. A high index of suspicion, and an early recourse to ultrasound examination and surgical intervention, might have saved the lives of those patients who died. PMID- 8513923 TI - Surgery for renal artery aneurysm. PMID- 8513924 TI - Peritoneal fluid: its relevance to the development of endometriosis. AB - OBJECTIVE: To review and evaluate published studies that have examined the role of peritoneal fluid (PF) in the development of endometriosis. DESIGN: Important studies related to this topic have been identified through a computerized bibliographical search (MEDLINE), as well as by manually scanning the published literature of major reproductive journals over the last several years. MAIN OUTCOME MEASURES: Studies that examined the effect of PF or its components on the pathophysiology of endometriosis are discussed. These include reported effects on the histogenesis, maintenance and proliferation of endometriosis, as well as related actions on infertility. RESULTS: The majority of investigations into the role PF plays in the pathogenesis of endometriosis have evaluated how it may adversely affect fertility. Suggestive but inconclusive data in the literature indicate that degenerating endometrial tissue may release a biochemical factor(s) into the peritoneal environment that is capable of inducing ectopic endometrium formation. Peritoneal fluid itself contains growth factor that may play a role in the implantation and maintenance of the ectopic endometrium. CONCLUSIONS: The PF of women with endometriosis has been shown to contain angiogenic as well as other growth factors. These compounds may contribute to the proliferation of the ectopic endometrium. PMID- 8513925 TI - Two years of assisted fertilization by partial zona dissection in male factor infertility patients. AB - OBJECTIVE: To assess partial zona dissection in our routine IVF-ET program over a 2-year period. DESIGN: Partial zona dissection before insemination on the day of oocyte collection or 24 hours after unsuccessful conventional IVF. In a subgroup of patients, oocytes were randomized to either partial zona dissection before insemination or IVF. SETTING: University infertility clinic. PATIENTS: Couples who suffered principally from male factor infertility or who had failed fertilization previously. INTERVENTIONS: Micromanipulation of oocytes with partial zona dissection. MAIN OUTCOME MEASURES: Comparison of fertilization rate, embryo morphology, and implantation rate between partial zona dissection inseminated oocytes and conventional IVF inseminated oocytes (controls). RESULTS: Five pregnancies were established in 199 patients. The incidence of polyspermy was significantly higher in the partial zona dissection group than in conventional IVF (4.8% versus 1.3%). There were no significant differences in the remaining parameters. The fertilization rate of partial zona dissection and reinsemination was significantly higher than conventional IVF insemination (13.6% versus 4.5%) but similar to the rate obtained when partial zona dissection was applied before insemination (13.6% versus 15.7%). CONCLUSIONS: Oocytes treated by partial zona dissection did not exhibit a greater fertilization rate than conventional IVF inseminated oocytes. Partial zona dissection may not be a useful technique for treating severe male factor infertility. PMID- 8513926 TI - Predicting success of gamete intrafallopian transfer. AB - OBJECTIVES: To examine seminal parameters predictive for success in a cycle of GIFT and to construct an algorithm using pertinent seminal data as well as easily obtained historical data to predict pregnancy and viable pregnancy rates. DESIGN: A retrospective study of 544 cycles in 376 couples. SETTING: A private IVF-ET and GIFT center. PATIENTS: Couples in a GIFT program with a mean of 53.6 months of infertility who had failed to conceive with other therapies. INTERVENTIONS: Gamete intrafallopian transfer. MAIN OUTCOME MEASURES: Pregnancy as a function of laboratory historical data with emphasis on seminal parameters. RESULTS: Motility was the only seminal parameter that was predictive. Success was correlated with the number of oocytes returned and inversely related to female age. An algorithm to predict pregnancy in a GIFT cycle as well as viable pregnancy was constructed. CONCLUSIONS: Motility is the only seminal parameter predictive for success in a GIFT cycle. An easily programmable algorithm can be constructed to help patient and physician decide on the appropriateness of GIFT for each couple. PMID- 8513927 TI - Relationship between embryo morphology and implantation rate after in vitro fertilization treatment in conception cycles. AB - OBJECTIVE: To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies. DESIGN: The study is based on information received from a computerized data base. SETTING: In Vitro Fertilization Unit, Sapir Medical Center, Kfar Saba, Israel. PATIENTS: A total of 117 consecutive pregnancies resulted from replacement of fresh embryos in our IVF-ET program. MAIN OUTCOME MEASURES: The impact of embryo quality, as assessed by morphological parameters, on the multiple pregnancy rate (PR). RESULTS: Implantation rates positively correlated with the number and the quality of transferred embryos. However, no multiple pregnancies occurred when only two embryos were replaced. There were no multiple pregnancies when only embryos of low quality (grades 1 and 2) were transferred. Furthermore, there was no correlation between the number of replaced embryos of poor quality and the rate of implantation. The multiple PR increased from 10% when a mixture of high and low quality embryos were transferred to 30.76% when only embryos of highest quality were transferred. CONCLUSION: The implantation rate of transferred embryos is directly correlated with the morphological scoring. The results of the study suggest that the number of embryos transferred should be balanced against their morphological quality to reduce the rate of multiple pregnancies. PMID- 8513928 TI - The natural history of multiple pregnancies after assisted reproduction: is spontaneous fetal demise a clinically significant phenomenon? AB - OBJECTIVE: To determine the rate of spontaneous fetal demise after heartbeats are demonstrated in multiple pregnancies conceived after IVF-ET. DESIGN: Retrospective case series. SETTING: University-based IVF-ET program. PATIENTS: Eighty-one patients in whom initial transvaginal ultrasound (US) study, performed at 5 to 6 weeks of gestation, identified more than one gestational sac. Total number of sacs was 191. INTERVENTION: Patients were followed by serial US examinations. MAIN OUTCOME MEASURE: Outcome of pregnancies. RESULTS: Twenty-four empty gestational sacs were identified in 21 patients, of whom 15 delivered, 2 miscarried, and 4 are currently ongoing beyond first trimester. Of the 167 initially viable embryos, 9 (5%) underwent spontaneous fetal demise. In 5 of these 9 pregnancies, initial US identified significant interfetal size variation. CONCLUSIONS: The rate of spontaneous fetal demise for a specific embryo in multiple gestation, after fetal heartbeats have been identified in early pregnancy, is 5%. This rate is similar to that seen in spontaneous conceptions. The chance of future fetal demise increases if first trimester interfetal size variation is significant. PMID- 8513929 TI - Conditions of oocyte storage and use of noninseminated as compared with inseminated, nonfertilized oocytes for the hemizona assay. AB - OBJECTIVES: To examine differences in sperm binding to the zona and recovery of oocytes from the storage vessel after oocyte preservation for the hemizona assay (HZA) by the method currently in predominant use, salt storage at 4 degrees C, as compared with a new method that should allow for indefinite preservation of zona receptors, dimethylsulphoxide (DMSO)/sucrose in liquid nitrogen (-196 degrees C). A second objective was to compare sperm binding to noninseminated zona as opposed to zona from inseminated, nonfertilized oocytes and to examine whether differences in binding potential were related to the patient's fertilization rate from the cycle in which the oocytes for the HZA originated. DESIGN: Binding and recovery were evaluated after 1, 2, 3, 6, 9, 12, and 17 to 25 months of storage. SETTING: In vitro fertilization and andrology laboratories at the University of Iowa Hospitals and Clinics; academic tertiary care center. RESULTS: Binding of sperm was significantly lower for nonfertilized oocytes stored > 12 months in salt at 4 degrees C than for those stored in liquid nitrogen. Binding was similar after storage for 1, 2, 3, 6, 9, and 12 months. Oocyte recovery was significantly lower after storage in salt for > 12 months as compared with storage in liquid nitrogen. Greater variability in sperm binding was observed between matching zona halves of nonfertilized as compared with noninseminated oocytes. Nonfertilized oocytes also bound fewer total sperm than noninseminated oocytes. The number of sperm bound to noninseminated oocytes was not related to the patient's fertilization rate from the cycle in which the oocytes originated. However, significantly fewer sperm bound to the zona of nonfertilized oocytes when the oocyte originated from a cycle in which the patient's fertilization rate was > 50%. CONCLUSIONS: These results indicate that storage of oocytes in DMSO/sucrose in liquid nitrogen results in superior long-term (> 12 months) preservation of zona receptors for sperm binding and improves oocyte recovery as compared with salt storage at 4 degrees C. Although noninseminated oocytes appear to be optimal for use in the HZA, nonfertilized oocytes can be used successfully if the oocytes originate from an IVF cycle in which the fertilization rate is < or = 50%. PMID- 8513930 TI - Effect of progesterone on human zona pellucida sperm binding and oocyte penetrating capacity. AB - OBJECTIVE: To determine if sperm exposure to P produces an enhancement in its fertilizing capacity. DESIGN: Sperm from fertile donors were exposed to P at 0.1 and 1.0 microgram/mL for 1 or 24 hours. The effects on hyperactivated (HA) motility at 1 and 4 hours, acrosome reaction (as determined by Pisum sativum agglutinin or T6/antibody techniques), on human zona pellucida binding (by using the hemizona assay), and on the penetrating ability (by using the zona-free hamster ova assay) were evaluated. RESULTS: Exposure to P at 1.0 microgram/mL enhanced HA motility after 1 and 4 hours of P exposure, the acrosome reaction after 24 hours' incubation, the number of sperm bound/hemizona after 1-hour incubation, and the penetration rates in the hamster ova assay at both incubation intervals. CONCLUSION: Sperm exposure to P enhances its fertilizing capacity in fertile men, and further investigation is warranted as a possible treatment for male factor patients. PMID- 8513931 TI - Sperm treatment with pentoxifylline improves the fertilizing ability in patients with acrosome reaction insufficiency. AB - OBJECTIVE: To test whether pentoxifylline, a drug previously shown to sensitize spermatozoa from normal samples to the action of acrosome reaction stimuli, can be used to improve the fertilizing ability of spermatozoa from patients with acrosome reaction insufficiency. DESIGN: Prospective analysis of pentoxifylline effects on the acrosome reaction and zona-free egg penetration; retrospective comparison of IVF results with and without the use of pentoxifylline. SETTING: Private hospital, public research center, and university-based laboratory. PATIENTS: In vitro fertilization patients selected on the basis of a previous acrosome reaction test. INTERVENTIONS: None in the experimental part; IVF-ET in the clinical part of this study. MAIN OUTCOME MEASURES: Frequency of the acrosome reaction, rate of penetration of zona-free eggs, normal fertilization in IVF attempts. RESULTS: Pentoxifylline improves the acrosome reaction scores and zona free egg penetration rates in patients with acrosome reaction insufficiency. Preliminary clinical experience shows an improvement of IVF results in these patients. CONCLUSIONS: In vitro pentoxifylline treatment of spermatozoa to be used in IVF improves the sperm fertilizing ability in patients with acrosome reaction insufficiency. However, the effect of pentoxifylline on the acrosome reaction should be tested individually in each patient before the application of the drug in this new indication. PMID- 8513932 TI - Induction of the acrosome reaction in human spermatozoa by human zona pellucida and effect of cervical mucus on zona-induced acrosome reaction. AB - OBJECTIVES: To investigate the induction of the acrosome reaction in human spermatozoa by the zona pellucida (ZP), cumulus oophorus, and cervical mucus (CM), and to examine the effect of cumulus oophorus and CM on the zona-induced acrosome reaction. DESIGN, PATIENTS, MAIN OUTCOME MEASURES: The acrosome status of spermatozoa from healthy donors that were cultured with salt-stored human ZP, cumulus oophorus, and/or cervical mucus was assessed using fluoresceinated pisum sativum agglutinin. RESULTS: The acrosome reaction rate after sperm attachment to the zona for 6 hours was 35.7% +/- 17.7%, which was higher than controls (2.8% +/ 1.9%). The acrosome reaction was not observed after passage through cumulus oophorus or CM; however, the acrosome reaction rate of spermatozoa passed through CM after the attachment to zona was 51.6% +/- 6.8%, a higher value in comparison with spermatozoa that had not passed through CM (25.6% +/- 9.4%). CONCLUSION: These data indicate that human ZP are capable of inducing the acrosome reaction in human spermatozoa; however, cumulus oophorus and CM are unable to do so. The data further provide evidence that CM promotes the zona-induced acrosome reaction in human spermatozoa. PMID- 8513933 TI - Writing and interpreting medical literature. PMID- 8513934 TI - Adherence of Escherichia coli to sperm: a mannose mediated phenomenon leading to agglutination of sperm and E. coli. AB - OBJECTIVE: To investigate the mechanism of adherence between Escherichia coli and sperm. DESIGN: Experimental study performed with donor sperm and male genital tract-derived E. coli. SETTING: Andrology unit of a university hospital. PATIENTS: None. INTERVENTIONS: Monitoring of sperm-E. coli agglutination; addition of sugars to block adherence; electron microscopy. MAIN OUTCOME MEASURE: Sperm-E. coli agglutination. RESULTS: Escherichia coli readily adhered to and agglutinated sperm. The phenomenon was observed at E. coli to sperm ratios as low as 1:20; maximum sperm agglutination involving approximately 90% of spermatozoa was seen with ratios of 1:5 or higher. By transmission electron microscopy, E. coli adherence was observed both on sperm heads and tails. Heteroagglutination could be blocked by D-mannose and alpha-methyl-mannopyranoside but not by other sugars. Preincubation of sperm or E. coli with mannose resulted in block of agglutination, indicating mannose-binding structures both on sperm and E. coli. CONCLUSIONS: Adherence of E. coli to sperm is mediated by mannose and mannose binding structures present on both cell types. Agglutination of sperm by E. coli may be relevant in male and female infertility. PMID- 8513935 TI - Interaction between human sperm cells and hamster oocytes after argon fluoride excimer laser drilling of the zona pellucida. AB - OBJECTIVES: To provide conclusive evidence that sperm cells gain access to the perivitelline space exclusively through a laser-drilled opening. To assess the optimal size of the hole and to evaluate the efficacy of laser drilling in comparison with that of mechanical zona dissection. DESIGN: An interspecies model of human sperm cell that interacts with a laser-drilled or partially zona dissected hamster oocytes. MAIN OUTCOME MEASURES: Penetration rate into the perivitelline space as related to the size of the opening (group A [5 microns], group B [10 microns], and group C [15 microns]) and to the sperm cell concentrations (1 x 10(6), 5 x 10(6), and 10 x 10(6) cells/mL) used for insemination. RESULTS: For each sperm cell concentration, the penetration rate into the perivitelline space was lowest for group A followed by group C and highest for group B. When penetration was compared for each hole size, it was found that sperm concentration had no effect on the rate of penetration in groups A and C but significantly affected this rate in group B. The highest penetration rate of 73% was observed with a concentration of 10 x 10(6) cell/mL and declined to 58% and 23% at 5 x 10(6) cell/mL and 1 x 10(6) cell/mL, respectively. Oocytes drilled by laser (10-microns hole) demonstrated a significantly higher penetration rate when compared with those treated by partial zona dissection (73% versus 20% and 58% versus 21% for sperm densities of 10 x 10(6) cells/mL and 5 x 10(6) cells/mL, respectively). CONCLUSION: Human sperm cells gain access into the perivitelline space of hamster oocytes exclusively through a hole drilled by an argon fluoride excimer laser. An opening of 10 microns was found to yield optimal results. Laser drilling of the zona pellucida seems to be superior to that of mechanical slitting in terms of sperm oolema interaction. PMID- 8513936 TI - Term pregnancy after fallopian tube transposition. AB - A 28-year-old woman suffered from pelvic pain and secondary infertility. She previously had right salpingo-oophorectomy because of ruptured right cornual EP. She was found to have a normal appearing left fallopian tube that entered into a noncommunicating residual horn of the uterus. Microsurgical transposition of the left tube and tubouterine implantation was performed successfully. For cases in which tubocornual anastomosis of the transposed tube is impossible because of previous cornual resection, our technique remains an option. PMID- 8513937 TI - Primary ovarian pregnancy after in vitro fertilization and embryo transfer: report of seven cases. AB - We have reported seven cases of ovarian pregnancy from among 116 EPs and 2,745 clinical pregnancies achieved after IVF and ET at Bourn Hall Clinic. All were associated with lower than normal serial levels of serum hCG and P. Transvaginal US scanning correctly made the diagnosis of ectopic gestation in all cases, and in five, ovarian pregnancy was suspected on the scan findings. Three patients were asymptomatic, whereas four complained of lower abdominal pain with or without vaginal discharge or bleeding. All patients were treated conservatively; four had ovarian wedge resection and three ovarian cystectomy. PMID- 8513938 TI - Proximal tubal occlusion by hysterosalpingogram: a role for falloposcopy. AB - Eight infertility patients with proximal tubal occlusion by HSG and at least one other independent method underwent falloposcopy to evaluate the etiology of uterotubal occlusion. Patency was established in 9 of 12 tubes evaluated. Falloposcopy revealed 5 tubes with multiple or extensive intratubal lesions that would be unsuitable for unilocular tubal resection with subsequent reanastomosis. In addition, 5 tubes were visually normal or had only minor pathological changes (2 of these patients became pregnant). Only 2 of the tubes examined in a single patient would be considered candidates for microsurgical correction at laparotomy. Falloposcopy will become a useful adjunct in the evaluation of the patient with suspected tubal infertility. It provides information regarding the condition of the tubal mucosa that is unavailable by any other technique, adding precision to surgical techniques when they are deemed necessary while directing other patients to assisted reproductive technologies. However, falloposcopy is still in its infancy and data from larger studies are needed. PMID- 8513939 TI - Human chorionic gonadotropin in commercial human menopausal gonadotropin preparations. AB - Several studies indicated the presence of an hCG-immunoreactive substance in commercial hMG preparations. Because hCG represents LH activity with a relatively very long half-life, differences between hMG preparations with respect to hCG content could imply clinical differences. To investigate whether there is any difference in this respect between the two most widely used hMG preparations, we measured the hCG content of ampules of Humegon and Pergonal retrieved from the market, together representing 51 separate production batches, with one or more different specific immunological assays. There are no significant differences between Humegon and Pergonal with respect to the mean hCG level per ampule as measured by RIA, ELISA, and Delfia. The batch-to-batch consistency for Humegon is higher. PMID- 8513940 TI - Levels of androgens and danazol metabolites in serum during danazol therapy. AB - Thirteen women who had endometriosis were treated with danazol (300 to 400 mg/d). Levels of androgens and danazol metabolites in serum and the influences of danazol metabolites on the assays for serum androgen were investigated during danazol therapy. Serum DHEAS significantly increased (P < 0.05), but serum DHEA slightly decreased. Serum T levels, measured by direct assay, were markedly elevated. However, measured after HPLC separation, the T levels in serum were significantly decreased (P < 0.05). There were considerable cross-reactions between danazol metabolites and androgens (T, DHEA, and A) in RIA. Purification of androgens using column chromatography was necessary to measure serum androgens precisely. PMID- 8513941 TI - Defining and interpreting pregnancy success rates for in vitro fertilization. AB - OBJECTIVES: To review current practice in describing pregnancy success rates after IVF-ET, to identify issues associated with interpreting these rates, and to suggest useful methods of describing these rates in the future. DESIGN: Review of literature concerning medical, epidemiologic, and statistical aspects of reporting IVF-ET pregnancy success rates. SETTING: The United States. PATIENTS: Infertile couples participating in IVF-ET. MAIN OUTCOME MEASURES: Usefulness and accuracy of IVF-ET pregnancy reporting. RESULTS: Several groups have collected information on the pregnancy success rates of IVF-ET clinics and have discussed appropriate definitions of pregnancy success. The largest of these groups in the United States is The American Fertility Society and its affiliate, the Society for Assisted Reproductive Technology. The number of live deliveries per 100 ET procedures and the number of live deliveries per 100 egg retrieval procedures are among the most commonly used definitions. CONCLUSION: The most commonly used definitions are particularly useful for describing the probability that a live infant will be delivered after IVF-ET is completed. To measure the effectiveness of the IVF-ET procedures and the costs of undergoing IVF-ET, other definitions are also important. Success rates need to be stratified by patient characteristics, such as age, that affect the probability of success. PMID- 8513942 TI - Difficult embryo transfer managed with a coaxial catheter system. AB - Our objective was the design of a catheter system that could be used in cases of a failed trial transfer. The system uses semirigid and soft-tipped materials that should allow atraumatic and reliable endometrial placement of embryos in difficult cases. PMID- 8513943 TI - Utero-ovarian vein blood sampling in postmenopausal women. AB - A technique for the collection of utero-ovarian vein blood in postmenopausal women is described. This technique enables the study of the endocrinology of postmenopausal ovaries and of the pelvic endocrine milieu. The sampling of blood from the utero-ovarian veins was almost always adequate, and there were no complications. PMID- 8513944 TI - Transport in vitro fertilization. PMID- 8513945 TI - Transport in vitro fertilization. PMID- 8513946 TI - Flak jacket for editors. PMID- 8513947 TI - Flak jacket for editors. PMID- 8513948 TI - Immunobead binding and antibody level. PMID- 8513949 TI - Statistical rubato and confidence intervals. PMID- 8513950 TI - "Round up the usual suspects!". PMID- 8513951 TI - Specificity of the immunobead test? PMID- 8513952 TI - Fertility drugs and ovarian cancer: red alert or red herring--new information. PMID- 8513953 TI - Endometriosis--narrow but deep--important? PMID- 8513954 TI - Endometriosis--narrow but deep--important? PMID- 8513955 TI - The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone. AB - OBJECTIVES: To examine the effects of food ingestion and administered dose on the absorption of oral micronized P (Utrogestan; Besins-Iscovesco, Paris, France) and to compare the bioavailability of intramuscular versus oral routes of administration. DESIGN: Prospective, randomized, open label crossover protocol with 7 days between dosages. SETTING: Academic institution. PARTICIPANTS: Fifteen normal postmenopausal women. INTERVENTIONS: All subjects participated in three separate protocols: [1] micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days; [2] micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and [3] micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days. MAIN OUTCOME MEASURES: Serum P concentrations were measured in all groups. RESULTS: Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC0 to 24) and the maximum serum P concentration (Cmax) without affecting time to maximum serum concentration (Tmax) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg. After intramuscular P, Cmax was higher and Tmax occurred later compared with the oral P preparation. Oral P had lower relative bioavailability (8.6%) than intramuscular P. CONCLUSIONS: Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-independent, dose proportionality being confirmed. Bioavailability of the oral P was approximately 10% compared with intramuscular P. PMID- 8513956 TI - Age-related changes in the metoclopramide-induced prolactin release in nulliparous women. AB - OBJECTIVE: To assess the metoclopramide-stimulated PRL response in nulliparous women as a function of chronological age (CA). DESIGN: Open and prospective study. SETTING: Outpatient endocrine clinic of a third level medical institution. PATIENTS: Fifty-one clinically healthy volunteer nulliparous women 15.8 to 48.2 years of age, with regular menses at least 1 year before the study (except 3 postmenopausal women) and no regular drug ingestion during the last 6 months, studied on days 18 to 22 of their menstrual cycle. INTERVENTIONS: After a 30 minute rest, three basal blood samples were obtained; oral metoclopramide (10 mg) was administered followed by subsequent blood samples at 60, 90, and 120 minutes. MAIN OUTCOME MEASURES: Duplicate serum PRL determinations were performed by RIA in all samples with P and E2 only in the pool of the basal samples. Hypothesis was formulated before data collection. RESULTS: All menstruating women had serum P levels > or = 4.0 ng/mL (> or = 12.72 nmol/L). A linear correlation was observed between CA and the serum PRL response, and also between CA and serum E2. Multiple regression analysis showed that CA and body mass index had the most marked effect on PRL response. Women < or = 25.0 years old had a serum PRL response and mean basal serum E2 levels lower than women > 25.1 years old. CONCLUSIONS: The metoclopramide-induced PRL response in nulliparous women augmented linearly as CA increased, suggesting a gradual decrease in the dopaminergic tone in older women, perhaps partially compensated by a high estrogen level to prevent an unrestrained rise in serum PRL levels. PMID- 8513957 TI - Oocyte maturation in humans: the role of gonadotropins and growth factors. AB - OBJECTIVE: To determine the effect of FSH/LH in vivo and epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) in vitro on human oocyte maturation. DESIGN: Oocyte-cumulus complexes were harvested from three different groups of patients: [1] unstimulated ovaries from women undergoing surgery; [2] multifollicular development achieved with a combination of FSH and LH in the absence of an ovulatory dose of hCG; and [3] oocyte-cumulus complexes retrieved after appropriate ovarian stimulation with FSH/LH and hCG for IVF purposes. SETTING, PATIENTS: In vitro fertilization program and patients undergoing surgery for benign disorders at the Instituto Valenciano de Infertilidad, Valencia, Spain. INTERVENTIONS: Oocyte-cumulus complexes from unstimulated ovaries collected at surgery by follicular puncture and washing. Oocyte-cumulus complexes from stimulated cycles obtained by ultrasound-guided transvaginal aspiration. Oocyte-cumulus complexes cultured in vitro in the absence or presence of different concentrations of EGF and IGF-I. MAIN OUTCOME MEASURE: Germinal vesicle breakdown and metaphase-II stage after 24 and 48 hours. RESULTS: Comparison of the spontaneous resumption of meiosis and metaphase II oocytes among groups showed significant differences between unstimulated and stimulated ovaries after 24 and 48 hours in culture. Administration of hCG accelerated the percentage of maturation by 24 hours. Further incubation of unstimulated oocyte-cumulus complexes with EGF and IGF-I significantly increased the percentage of metaphase II oocytes after 24 and 48 hours in culture. CONCLUSIONS: Epidermal growth factor and IGF-I are able to augment spontaneous maturaion in immature human oocytes. Because spontaneous maturation is mainly observed when follicles have been exposed to pharmacological doses of hMG, it is suggested that increasing FSH levels within the follicle is coincident with the generation of a positive signal necessary to complete oocyte maturation in humans. This signal may be linked to the dynamics of growth factors within the follicle itself. PMID- 8513958 TI - Human growth hormone enhances progesterone production by human luteal cells in vitro. II. Evidence of a distinct effect on two luteal cell types. AB - OBJECTIVE: To examine the differential effect of human GH (hGH) on basal and hCG stimulated production by cultured small and large human luteal cells. DESIGN: Distinct cultures of small and large luteal cells from early and midluteal phase. SETTING: All corpora lutea were obtained from the Obstetrics and Gynecology Department of the Catholic University, a public care center in Rome, Italy. PATIENTS, PARTICIPANTS: Ten nonpregnant women between 31 and 43 years of age underwent surgery for various nonendocrine disorders such as leiomyomatosis. INTERVENTIONS: Corpora lutea were obtained at the time of hysterectomy. MAIN OUTCOME MEASURES: Small and large luteal cells were incubated with or without hCG and/or hGH at different concentrations. RESULTS: Human GH neither at 250 nor at 500 micrograms/L increased basal P production by small luteal cells, whereas from 1,000 micrograms/L, P concentration in media was significantly increased. The concomitant treatment with ineffective doses of hCG (30 and 60 IU/L) and hGH (250 and 500 micrograms/L) enhanced P production to that obtained with the highest doses of hGH (1,000 micrograms/L or more) or hCG (125 to 250 IU/L) alone. Human GH addition did not change the amount of P release by large luteal cells at any concentration. CONCLUSIONS: These results indicate a distinct and differential effect of hGH on in vitro luteal steroidogenesis by the two luteal cell types. PMID- 8513959 TI - Growth hormone response to L-dopa and pyridostigmine in women with polycystic ovarian syndrome. AB - OBJECTIVE: To evaluate the GH secretion and clarify the factors influencing the GH secretion in women with polycystic ovarian syndrome (PCOS). DESIGN: Comparison of the GH response to L-dopa with or without pyridostigmine (inhibitor of acetylcholinesterase) pretreatment and insulin response to oral glucose tolerance test in patients with PCOS and matched controls. SETTING: Outpatients and healthy volunteers studied at a clinical research unit of a university hospital. PATIENTS, PARTICIPANTS: Ten women with PCOS and 9 controls with regular cycles were recruited. INTERVENTIONS: After an overnight fast, each subject underwent a GH stimulation test with L-dopa with or without pyridostigmine pretreatment. Plasma insulin and glucose levels were measured after a 75-g glucose load. MAIN OUTCOME MEASURES: Plasma GH, insulin-like growth factor I (IGF-I), insulin, and nonesterified fatty acids. RESULTS: Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in PCOS than those in controls. Pyridostigmine enhanced the GH response to L-dopa significantly in PCOS. Insulin responses and insulin AUC to oral glucose load were significantly higher in PCOS than those in controls. Plasma IGF-I levels of PCOS were significantly higher than controls. Insulin AUC had a positive correlation with plasma IGF-I levels but an inverse correlation with GH AUC in PCOS and controls. CONCLUSION: Our result indicated that decreased GH secretion of PCOS may be associated with a high somatostatin activity and a high plasma IGF-I level. PMID- 8513960 TI - Estrogen and progesterone receptors in endometriotic tissue and endometrium: comparison according to localization and recurrence. AB - OBJECTIVE: To study the hormonal regulation of primary and recurrent endometriosis by comparing the levels of estrogen receptors (ER) and progesterone receptors (PR) with the levels in uterine endometrium obtained simultaneously. DESIGN: Tissue samples collected at routine operations. SETTING: One university clinic. PATIENTS: A total of 69 endometriotic samples were obtained from 61 women, and endometrium was obtained from 54 of the women. Seventeen of the patients (26%) had a recurrent disease; the others (n = 49) were operated on for the first time. MAIN OUTCOME MEASURES: Samples from recurrences constituted 18% (6/34) of the endometriomas, 37% (10/27) of the biopsies from ovarian lesions, and 4 of 5 biopsies from peritoneal endometriosis. In primary endometriotic lesions, both ER and PR were significantly lower than in endometrium. In recurrent lesions, ER levels in cytosol were significantly lower than in endometrium, but there was no difference concerning PR. In endometriotic tissue, the PR level was significantly higher in recurrent than in primary tissue, but there was no difference concerning ER. The ER level was significantly lower in ovarian but not in peritoneal endometriosis, compared with endometrium. No difference was seen concerning PR. CONCLUSION: This study shows differences in ER and PR levels in primary and recurrent endometriosis and indicates a different hormonal regulation of the two stages of the disease. PMID- 8513961 TI - Estrogen and progesterone receptors in human decidua after RU486 treatment. AB - OBJECTIVE: To examine RU486 action on decidua at the level of cellular estrogen receptor (ER) and P receptor (PR). DESIGN: Controlled basic study for contragestion mechanism of mifepristone. SETTING: Normal human volunteers in an academic research environment. PATIENTS: Sixty women with 6 to 7 weeks of gestation who voluntarily requested termination of pregnancy were recruited and randomly divided into three groups. INTERVENTION: A single dose of 200 mg RU486 was orally administered to the two treatment groups 12 and 24 hours, respectively, before surgical interruption of pregnancies. Placebo was used for control group. Decidual tissues were collected right after operation. MAIN OUTCOME MEASURE: Immunocytochemical reactions of PR and ER in decidua after RU486 treatment were compared with the control subjects. The differences of the reaction in decidual area with or without trophoblast invasion were noted. RESULTS: RU486 treatment increased PR and ER staining in vessel and stroma of decidua without trophoblast invasion (decidua parietalis) but not in decidua with trophoblast invasion (decidua capsularis or basalis). Chi-squared analysis indicated a significant increase in the number of ER-positive samples after RU486 treatment. CONCLUSION: The decidua parietalis was the primary target site of RU486. The lack of RU486 effect on decidua capsularis implied that trophoblast invasion prevented against antiprogestin impact. PMID- 8513962 TI - A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. AB - OBJECTIVES: To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up. DESIGN: Open-label, randomized trial. SETTING: University hospital endometriosis center. PATIENTS: Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. INTERVENTIONS: Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up. MAIN OUTCOME MEASURES: Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale. RESULTS: At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups. CONCLUSIONS: Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal. PMID- 8513963 TI - Reproductive outcome after laparoscopic local methotrexate injection for tubal pregnancy. AB - OBJECTIVE: To evaluate reproductive outcome after laparoscopic local methotrexate (MTX) injection for tubal pregnancy. DESIGN: Follow-up was performed after 77 women were treated with local MTX injection between January 1, 1987 and December 31, 1990. SETTING: Department of Obstetrics and Gynecology in a university medical center. MAIN OUTCOME MEASURES: Concise patient details about tubal patency in hysterosalpingography, pelvic findings at laparoscopy or laparotomy performed after the treatment, and the intrauterine and extrauterine pregnancy rates (PRs) are given. RESULTS: Intrauterine PR of 67% and extrauterine PR of 13% were achieved. CONCLUSION: Local MTX injection does not modify tubal or pelvic anatomy and does not impair subsequent reproductive performance. PMID- 8513964 TI - Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. AB - OBJECTIVE: To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. DESIGN: Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. SETTING: All patients were referred to our outpatient clinic affiliated with the university hospital. RESULTS: The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. CONCLUSION: Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation. PMID- 8513965 TI - Adhesion formation after laparoscopic electrocoagulation of the ovarian surface in polycystic ovary patients. AB - OBJECTIVE: To evaluate the incidence and extent of periovarian adhesion formation subsequent to laparoscopic electrocoagulation of the ovarian surface in infertility patients with polycystic ovarian disease (PCOD). DESIGN: From a total of 199 PCOD patients treated with ovarian electrocautery, 50 cases of laparoscopy and 12 cesarean sections served as second-look investigation. A subgroup of 30 patients had abdominal lavage and artificial ascites after surgery; they underwent "early" second-look (2 to 14 days after laparoscopy). SETTING: All patients were referred to our fertility outpatient clinic affiliated with the university hospital. PATIENTS: Infertility patients with polycystic ovarian reaction to hormonal stimulation therapy underwent laparoscopic electrocoagulation of the ovarian surface. RESULTS: Adhesion formation was detected in 19.3%; the incidence reduced to 16.6% with the use of abdominal lavage. The adhesions found were obviously due to bleeding of the ovarian capsule caused by electrocautery. Adhesiolysis was easily possible during "early" second look. CONCLUSION: The incidence of de novo adhesion formation caused by laparoscopic electrocoagulation of the ovarian surface seems to be lower than after ovarian wedge resection; it can be reduced by abdominal lavage and artificial ascites. PMID- 8513966 TI - Long-term recall of time-to-pregnancy. AB - OBJECTIVE: To validate two versions of a short self-completion questionnaire on time-to-pregnancy. DESIGN: Information from the questionnaire was compared with concurrently collected data from the same individuals. POPULATION: Questionnaires were sent to 1,647 women who continue to be followed up by the Oxford Family Planning Association Contraceptive Study. Replies were received from 1,498, a response rate of 91.0%. Successful matching was achieved with 1,392 pregnancies that met the study criteria and that had values of time-to-pregnancy in both data sources. Median recall time was 14 years (interquartile range, 11 to 16 years). MAIN OUTCOME MEASURES: At the group level, the frequency distributions of time-to pregnancy from the two sources are presented as cumulative percentages. At the individual level, the distribution of discrepancies between the sources is tabulated separately for each value of time-to-pregnancy, and accuracy of detection of clinical subfertility is presented (sensitivity and specificity). RESULTS: At the group level, remarkably good agreement was found between the two sources of information. Digit preference was present to a limited degree. There were no important differences between the two questionnaire versions. At the individual level, some misclassification was evident. For the detection of clinical infertility, sensitivity was 79.9% and specificity was 94.9%. CONCLUSIONS: Short, self-completion questionnaires are remarkably accurate for assessing time-to-pregnancy at a group level. Individual-level misclassification is frequent, but detection of clinical subfertility is fairly accurate. PMID- 8513967 TI - Inhibition of glucose-induced insulin secretion through inactivation of glucokinase by glyceraldehyde. AB - D-Glyceraldehyde irreversibly inhibited rat liver glucokinase in a concentration dependent manner. The inactivation of glucokinase by glyceraldehyde was blocked by the presence of its substrates such as glucose and mannose. Glucokinase was highly sensitive to glyceraldehyde compared with some other glycolytic enzymes (from animal tissues) including hexokinase, glucose-6-phosphate isomerase, 6 phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase. The amino acid analysis of untreated and glyceraldehyde-treated glucokinase suggested that glyceraldehyde-induced inactivation of glucokinase is caused by glycation of Lys residues of the enzyme by the triose. Treatment of pancreatic islets with 6 mM glyceraldehyde for 1 h at 37 degrees C caused both inactivation of glucokinase and inhibition of glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets, however, was little affected by glyceraldehyde. In addition, glyceraldehyde did not affect the insulin secretory responses of islets to nonglucose secretagogues such as glyceraldehyde and Leu. When pancreatic islets were cultured with a lower concentration (1 mM) of glyceraldehyde for a longer time (17 h) in the presence of 10 mM glucose to mimic the in vivo conditions, both glucokinase activity and glucose-induced insulin secretion were again decreased. This study demonstrates that glucose-induced insulin secretion is impaired by glyceraldehyde through the inactivation of glucokinase. The implication of this finding in the pathophysiology of type II diabetes is discussed. PMID- 8513968 TI - Time course of increased lipid and decreased glucose oxidation during early phase of childhood obesity. AB - To determine the time course of metabolic dysfunctions in recent active obesity, we studied basal energy expenditure and lipid and glucose oxidation in 31 obese children (duration of obesity 1-11.5 yr), compared with 14 lean age-matched control subjects. Using indirect calorimetry in basal overnight fasting conditions, we found that obese children produced 15% more energy than control subjects. Obese children oxidized twice as much lipid (56 +/- 4 mg/min) as normal children (25 +/- 5 mg/min, P < 0.0005), so that lipid oxidation provided 61 +/- 6% of overall energy production (vs. 33 +/- 3% in control subjects, P < 0.0005). This increase of lipid oxidation was already present in the earlier stages of obesity. Glucose oxidation was diminished in the obese (93 +/- 6 mg/min) compared with the control children (136 +/- 6 mg/min, P < 0.0005) and accounted for only 39 +/- 3% of energy production (67 +/- 6% in control subjects, P < 0.0005). This decrease was not present initially and appeared after approximately 4 yr and worsened with obesity duration (r = 0.72, P < 0.0005). The results were similar when lipid and glucose oxidation were normalized to body surface area or lean body mass. We hypothesize that increased lipid oxidation is one of the earlier dysfunctions observed in recent-onset obesity and that lipid oxidation may induce a progressive decrease of glucose oxidation, insulin resistance, and increased fasting insulin secretion. PMID- 8513969 TI - Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function. AB - Evidence is increasing for small-vessel disease and disturbance of endothelium dependent vasodilation in diabetic patients. The aim of this study was to compare coronary circulation in 11 diabetic patients (6 type I and 5 type II) and 7 control subjects. All patients had normal left ventricular systolic function and angiographically normal coronary arteries. To evaluate the maximal area of coronary microcirculation, coronary vascular reserve was determined by intracoronary Doppler and a maximally vasodilating dose of intracoronary papaverine (peak-to-resting coronary flow velocity ratio). To assess coronary endothelial function responses to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) M coronary estimated concentrations) were analyzed on four different segments in each patient by quantitative angiography. Peak-to-resting coronary flow velocity ratio was lower in diabetic patients than in control subjects (3.9 +/- 0.9 and 5.0 +/- 0.7, respectively, P < 0.02). Acetylcholine did not produce any diameter change at 10(-8) and 10(-7) M, but a progressive diameter reduction was observed at 10(-6) and 10(-5) M (-8.0 +/- 15.2%, P < 0.02 and -24.0 +/- 13.6%, P < 0.001, respectively). In control subjects, a progressive diameter dilation was produced from 10(-8) to 10(-6) M acetylcholine (5.1 +/- 3.4, 12.1 +/- 7.0, and 16.4 +/- 7.3%, respectively, all P < 0.001), and a moderate reduction was observed at 10(-5) M (-4.9 +/- 7.5%, P < 0.02). In the two groups, all segments dilated similarly after intracoronary isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513970 TI - Transport of insulin across rabbit nasal mucosa in vitro induced by didecanoyl-L alpha-phosphatidylcholine. AB - To investigate the short-term effects of didecanoyl-L-alpha-phosphatidylcholine on the nasal mucosa and the mechanism by which didecanoyl-L-alpha phosphatidylcholine enhances the nasal absorption of insulin, an in vitro model was developed. The mucosa from the posterior part of the rabbit nasal septum was mounted in an Ussing chamber and incubated in bicarbonate Ringer solution at 37 degrees C. Potential difference, transmucosal conductance, and unidirectional tracer fluxes were measured across an exposed tissue area of 0.44 cm2. Morphological and physiological examinations revealed a typical respiratory epithelium containing amiloride-sensitive Na+ channels and diphenylamine-2 carboxylate-sensitive Cl- channels. Spontaneous potential difference (10.8 +/- 0.4 mV [n = 50]; serosa positive) and transmucosal conductance (10.5 +/- 0.4 mS/cm2 [n = 50]) were stable for several hours. Mucosal addition of 0.1-0.5% didecanoyl-L-alpha-phosphatidylcholine increased transmucosal conductance (by 43 53%) and decreased potential difference (to 0-2 mV) to new steady-state values within 10-15 min. Control unidirectional rate constants for permeation of sucrose, polyethylene glycol 4000, and insulin were low and varied according to the molecular size. After addition of didecanoyl-L-alpha-phosphatidylcholine, unidirectional rate constants for the three compounds all increased 3- to 5.5 fold. The didecanoyl-L-alpha-phosphatidylcholine effects on potential difference and transmucosal conductance were reversible after a recovery period of at least 40 min when didecanoyl-L-alpha-phosphatidylcholine had been applied to the mucosal side for 15 min. The results suggest that didecanoyl-L-alpha phosphatidylcholine may increase the transepithelial absorption of insulin by facilitating a paracellular passage through a reversible opening of tight junctions. PMID- 8513971 TI - Human skeletal muscle insulin receptor substrate-1. Characterization of the cDNA, gene, and chromosomal localization. AB - Insulin receptor substrate-1 is a major substrate of insulin receptor Tyr kinase. We have now cloned the IRS-1 cDNA from human skeletal muscle, one of the most important target tissues of insulin action, localized and cloned the human IRS-1 gene, and studied the expression of the protein in Chinese hamster ovary cells. Human IRS-1 cDNA encodes a 1242 amino acid sequence that is 88% identical with rat liver IRS-1. The 14 potential Tyr phosphorylation sites include 6 Tyr-Met-X Met motifs and 3 Tyr-X-X-Met motifs that are completely conserved in human IRS-1. Human IRS-1 has > 50 possible Ser/Thr phosphorylation sites and one potential ATP binding site close to the NH2-terminal. The human IRS-1 gene contains the entire 5'-untranslated region and protein coding region in a single exon and was localized on chromosome 2 q36-37 by in situ hybridization. By Northern blot analysis, IRS-1 mRNA is rare and consists of two species of 6.9 and 6 kilobase. By using quantitative polymerase chain reaction after reverse transcription of total RNA from human fetal tissues, IRS-1 mRNA could be identified in all tissues. When human IRS-1 cDNA was expressed in Chinese hamster ovary cells, the protein migrated between 170,000-180,000 M(r) in sodium dodecyl sulfate polyacrylamide gel electrophoresis and was rapidly Tyr phosphorylated upon insulin stimulation. Thus, IRS-1 is widely expressed and highly conserved across species and tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513972 TI - Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy. AB - To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513973 TI - GLUT2 expression and function in beta-cells of GK rats with NIDDM. Dissociation between reductions in glucose transport and glucose-stimulated insulin secretion. AB - GLUT2 underexpression has been reported in the beta-cells of Zucker diabetic fatty rats and db/db mice, models of spontaneously occurring NIDDM with antecedent obesity. To determine whether the beta-cells of a nonobese rodent model of NIDDM exhibit the same abnormalities in GLUT2, we studied Goto-Kakizaki rats. In these mildly diabetic animals glucose-stimulated insulin secretion was reduced at all ages examined from 8 to 48 wk. In normal control Wistar rats, immunostainable GLUT2 was present on all insulin-positive cells in the pancreatic islets. Only 85% of beta-cells were GLUT2-positive in GK rats at 12 wk of age, and only 34% were positive at 48 wk of age. GLUT2 mRNA was 50% of normal in 12-wk old GK rats. In the latter age-group, glucose-stimulated insulin secretion was only 28% of normal at a time when 85% of beta-cells were GLUT2-positive and initial 3-O-methyl-D-glucose transport rate was 77% of the control value. We conclude that although GLUT2 is underexpressed, neither the magnitude of the underexpression of GLUT2 nor of the reduction in GLUT2 transport function in islets of GK rats is sufficient by itself to explain the profound reduction in glucose-stimulated insulin secretion. PMID- 8513974 TI - Effects of hyperinsulinemia on muscle fiber composition and capitalization in rats. AB - Statistical studies repeatedly have shown an association between systemic insulin resistance and a preponderance of highly glycolytic, relatively insulin insensitive muscle fibers as well as a low density of muscle capillaries. The nature of the relationship between these observations is, however, not clear. Female rats were made hyperinsulinemic for 7 days by implantation of osmotic minipumps. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy was controlled with glucocorticoid substitution. This resulted in hyperinsulinemia and moderate hypoglycemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity was increased and measured with a hyperinsulinemic-euglycemic clamp technique. This was paralleled by an elevated glucose utilization estimated as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and inguinal adipose tissues and the soleus and extensor digitorum longus muscles. Glycogen synthesis was also elevated in the soleus muscle. Muscle fiber composition changed with hyperinsulinemia and elevated 2-deoxyglucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminished. Capillary density was elevated per unit muscle surface area as well as per muscle fiber. This was paralleled by increased insulin sensitivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber composition is of importance for insulin sensitivity in muscle. PMID- 8513975 TI - Effect of glucocorticoid and growth hormone treatment on proinsulin levels in humans. AB - Treatment with glucocorticoids is associated with a disproportionate elevation in the PI/IRI ratio. To determine whether growth hormone--another agent capable of producing insulin resistance and changing B-cell function--also alters the PI/IRI ratio and whether growth hormone and glucocorticoids have a synergistic effect on PI and IRI levels, we examined these variables in four groups of young healthy subjects (n = 8/group) after 7 days of treatment with placebo, prednisone (0.8 mg.kg-1 x day-1), rhGH (0.1 mg.kg-1 x day-1), and the combination of prednisone and rhGH. Fasting plasma glucose levels increased significantly above those of the control group in subjects receiving prednisone or prednisone and rhGH but not in subjects receiving rhGH alone. The basal concentration of IRI increased in response to prednisone, rhGH, and the combination of prednisone and rhGH. However, this increase in IRI was largely due to an increase in PI, so that the PI/IRI ratio increased from 14.7 +/- 2.4% in control subjects to 33.9 +/- 5.3% in subjects on prednisone (P < 0.005), 40.9 +/- 4.3% in individuals receiving rhGH (P < 0.001 vs. control subjects), and 58.1 +/- 9.2% in subjects receiving both prednisone and rhGH (P < 0.001 vs. control subjects). We suggest that this change in PI/IRI with glucocorticoid and growth hormone treatment may be due to an alteration in B-cell synthesis or release of PI. This change in the PI/IRI ratio is not dependent on fasting hyperglycemia but may contribute to the hyperglycemia often observed with these agents. Furthermore, these data show that IRI is not a reliable indicator of true insulin levels or insulin sensitivity in either growth hormone- or glucocorticoid-treated subjects. PMID- 8513976 TI - Superantigen-like effects and incidence of diabetes in NOD mice. AB - The population of T-cells that develops in any individual can be divided into families based on sequence differences in the beta-chain variable region of the T cell receptor heterodimer. Major histocompatibility complex products and endogenous retroviral gene products have both been shown to exert powerful influences on the frequency distribution of T-cell receptor beta-chain variable region families in the mouse. In most mouse strains, these repertoire modifiers appear to be fully functional early in mouse development and shape a repertoire of antigen specificities that remains essentially unchanged from the first weeks of life until old age. In NOD mice, an inbred mouse model of type I diabetes, puberty in males coincides with a beta-chain variable region-specific T-cell expansion that mimics the results of exposure to exogenous superantigens in immunologically mature animals. The subsequent behavior of this subset indicates that it may play a role in the relative protection of male NOD mice from complete pancreatic beta-cell destruction and overt diabetes. PMID- 8513977 TI - Regulation of glucose uptake and metabolism by working muscle. An in vivo analysis. AB - To assess the mechanisms whereby muscular work stimulates glucose uptake and metabolism in vivo, dogs were studied during rest (-40-0 min), moderate exercise (0-90 min), and exercise recovery (90-180 min) with plasma glucose clamped at 5.0, 6.7, 8.3, and 10.0 mM (n = 5 at 5.0 mM and n = 4 at all other levels) using a variable glucose infusion. Basal insulin was maintained with somatostatin and insulin replacement. Whole-body glucose uptake, limb glucose uptake, and oxidative and nonoxidative glucose plus lactate metabolism, were assessed with tracers ([3H]glucose and [14C]glucose) and arteriovenous differences. The combined effects of glucose and exercise on the increment above resting values for limb glucose uptake, arteriovenous glucose difference, LGO, LGNO, and rate of glucose disappearance were synergistic (approximately 112, 90, 125, 76, and 90% greater than the additive values, respectively). Neither exercise nor recovery affected the Km for limb glucose uptake (4.7 +/- 1.1, 4.8 +/- 0.4, and 5.2 +/- 0.3 mM during rest, exercise, and recovery, respectively), but both conditions increased the Vmax (44 +/- 16, 217 +/- 30, and 118 +/- 14 mumol/min during rest, exercise, and recovery, respectively). Similarly, the Km for arteriovenous glucose differences were unaffected by exercise recovery (4.9 +/- 0.6, 5.0 +/- 0.4, and 5.3 +/- 0.3 mM during rest, exercise, and recovery, respectively), but the maximum rose (272 +/- 50, 650 +/- 78, and 822 +/- 111 microM during rest, exercise, and recovery, respectively). The LGO was unchanged by glycemia at rest (15 +/- 4 mumol/min at 10.0 mM). The Km for LGO during exercise was 5.1 +/- 0.3 mM, and the Vmax was 163 +/- 15. The capacity for LGO returned to basal during recovery. LGNO increased gradually with increasing glycemia during rest, exercise, and recovery and did not approach saturation (38 +/- 13, 105 +/- 36, and 132 +/- 45 mumol/min during rest, exercise, and recovery, respectively, at 10.0 mM). In general, the LGNO was elevated at every glucose level during exercise (approximately twofold) and recovery (approximately threefold) compared with rest. Arterial free fatty acid and glycerol levels decreased with increasing glycemia within all periods. Free fatty acids were suppressed by a greater amount during exercise compared with rest and recovery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8513978 TI - Glycosylation of Asn397 or Asn418 is required for normal insulin receptor biosynthesis and processing. AB - Two N-linked sites of glycosylation in the insulin receptor were examined for their contribution to insulin binding, tyrosine kinase activity, and receptor biosynthesis. Asn397 and Asn418 were replaced by Gln using site-directed mutagenesis either as single mutations, i.e., Q-397 and Q-418, or as a double mutation in which both sites were removed (Q-D). The mutations were transiently expressed in COS cells and the findings compared with cells that transiently expressed the wild-type human insulin receptor. Q-397 and Q-418 mutant insulin receptors had insulin-binding characteristics similar to the wild-type human insulin receptor, whereas no insulin-binding activity could be detected above the control level in cells transfected with Q-D. Flow cytometry with antibodies against the human insulin receptor indicated the presence of Q-397, Q-418, and wild-type human insulin receptors in the surface of COS cells and failed to demonstrate a Q-D receptor. Insulin-induced autophosphorylation was similar in Q 397, Q-418, and wild-type human insulin receptors as was their ability to phosphorylate an artificial substrate, poly Glu-Tyr (4:1). Our inability to detect Q-D receptors was not caused by a lack of Q-D mRNA. COS cells transfected with Q-D cDNA generated as much Q-D mRNA as the amount of wild-type human insulin receptor mRNA present in cells transfected with wild-type receptor cDNA. Finally, pulse-chase experiments with [35S]Met were able to detect 190,000-M(r) proreceptors and the alpha-subunits for Q-397, Q-418, and wild-type human insulin receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513979 TI - The paradox between resistance to hypoxia and liability to hypoxic damage in hyperglycemic peripheral nerves. Evidence for glycolysis involvement. AB - Isolated ventral and dorsal rat spinal roots incubated in normal (2.5 mM) or high glucose (25 mM) concentrations or in high concentrations of other hexoses were exposed transiently to hypoxia (30 min) in a solution of low buffering power. Compound nerve action potentials, extracellular direct current potentials, and interstitial pH were continuously recorded before, during, and after hypoxia. Ventral roots incubated in 25 mM D-glucose showed resistance to hypoxia. Dorsal roots, on the other hand, revealed electrophysiological damage by hyperglycemic hypoxia as indicated by a lack of posthypoxic recovery. In both types of spinal roots, interstitial acidification was most pronounced during hyperglycemic hypoxia. The changes in the sensitivity to hypoxia induced by high concentrations of D-glucose were imitated by high concentrations of D-mannose. In contrast, D galactose, L-glucose, D-fructose, and L-fucose did not have such effects. Resistance to hypoxia, hypoxia-generated interstitial acidification, and hypoxia induced electrophysiological damage were absent after pharmacological inhibition of nerve glycolysis with iodoacetate. These observations indicate 1) that enhanced anaerobic glycolysis produces resistance to hypoxia in hyperglycemic peripheral nerves and 2) that acidification may impair the function of peripheral axons when anaerobic glycolysis proceeds in a tissue with reduced buffering power. PMID- 8513980 TI - Physiological increments in plasma insulin concentrations have selective and different effects on synthesis of hepatic proteins in normal humans. AB - These studies tested the hypothesis that physiological increments in plasma insulin concentrations have selective effects on the synthesis of hepatic proteins in humans. Leucine kinetics and fractional synthetic rates of albumin, fibrinogen, antithrombin III, and apoB-100 were determined in 6 normal subjects, on two different occasions during either the infusion of saline (control study) or a euglycemic-hyperinsulinemic (0.4 mU.kg-1 x min-1 for 240 min) clamp, by a primed-constant infusion of [1-14C]Leu. The insulin infusion significantly decreased the rates of nonoxidative Leu disposal (1.70 +/- 0.10 vs. control 2.06 +/- 0.09 mol.kg-1 x min-1), increased the albumin (7.2 +/- 0.4 vs. 6.2 +/- 0.6%/day), decreased the fibrinogen (18 +/- 1 vs. 23 +/- 2%/day), and antithrombin III (28 +/- 3 vs. 40 +/- 4%/day) fractional synthetic rate, whereas it did not affect the total apoB-100 (49 +/- 5 vs. 52 +/- 6%/day) fractional synthetic rate. Thus, the insulin-induced decrement in the estimates of whole body protein synthesis (nonoxidative Leu disposal) represents the mean result of opposite effects of hyperinsulinemia on the synthesis of proteins with different functions. The positive effect of insulin on albumin synthesis may play an important anabolic role during nutrient absorption by promoting the capture of a relevant amount of dietary essential amino acids into the protein, whereas the negative effect of insulin on fibrinogen synthesis might, at least partially, account for the increased plasma fibrinogen concentrations previously reported in poorly controlled diabetic patients. PMID- 8513981 TI - The effect of intravenous omeprazole on the gastric and duodenal potential difference and pH in healthy subjects. AB - The effect of intravenous omeprazole (40 and 80 mg) on the gastric and duodenal potential difference (PD) and pH was investigated in 9 healthy volunteers. Gastric PD and pH increased significantly (p < 0.05) following omeprazole, and the increases were equal following the two doses. No changes were found in duodenal PD or pH. It has been claimed that gastric PD changes following acid secretion inhibition with cimetidine and glucagon might be due to changes in the parietal cell surface area. Omeprazole causes no changes in the parietal cell structure, and the changes in gastric PD following omeprazole might therefore be ascribed to changes in mucosal electrophysiologic transport or resistance. PMID- 8513982 TI - Duodenal bicarbonate secretion induced by human epidermal growth factor in rats is partially mediated by prostaglandins. AB - In the present study, the effect of graded intravenous infusions of human epidermal growth factor (hEGF) 0.005, 0.05 and 0.25 micrograms/ml, with or without 4 mg/kg i.p. indomethacin pretreatment, on rat duodenal bicarbonate secretion was investigated. Perfused duodenal loops were prepared in rats which were given intravenous infusions of hEGF with or without indomethacin. Duodenal pH and pCO2 were measured at 5-min intervals for 45 min, and bicarbonate secretion was calculated. Compared to control, each dose of hEGF caused a significant dose/response rise of duodenal bicarbonate secretion. Prostaglandin release was abolished by indomethacin pretreatment. Indomethacin-pretreated rats had a significant reduction of bicarbonate secretion which was still higher than in controls. These results provide evidence that duodenal bicarbonate secretion induced by hEGF is only partly accounted for by a prostaglandin-dependent mechanism. PMID- 8513983 TI - Role of nitric oxide and prostaglandins in gastroprotection induced by capsaicin and papaverine. AB - Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) and the present study was designed to determine the possible role of nitric oxide (NO) and prostaglandins (PG) in the protective and hyperemic effects of capsaicin and papaverine on rat gastric mucosa. We found that the pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose dependently the area of ethanol-induced lesions, the ED50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous injection of N omega-nitro-L-arginine (L-NNA; 1.2-5 mg/kg), a selective blocker of NO synthase, which by itself caused only a small increase in ethanol lesions, reversed dose dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i.v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8513984 TI - A plethora of GTPases, large and small. AB - It has become apparent recently that a variety of small GTPases (small GTP binding proteins or smgs), related to the oncogene ras, are involved in many cellular functions, especially membrane traffic and cytoskeleton regulation. This review will summarize some of the major themes that are emerging, focusing on the presence and possible functions of these smgs in the gastrointestinal tract. In addition, new cellular locations and functions for heterotrimeric G-proteins, previously believed to be solely associated with plasma membrane receptors, are becoming evident and will be discussed here. PMID- 8513985 TI - Enhanced H+ diffusion by NH4+/HCO3-: implications for Helicobacter-pylori associated peptic ulceration. AB - The in vitro effect of ammonium bicarbonate buffer on mucus H+ permeability is reported here. The diffusional resistance of mucus and water was demonstrated to be dependent on buffer concentration, and the contrast between the two types of layers was most pronounced for low buffer concentration near neutrality. Moreover, the pKa values of HCO3- and NH3 had a profound effect on measured DHCl. These in vitro studies suggest that a potentially damaging high local concentration of NH3 and HCO3- within the mucus layer generated by the action of Helicobacter pylori urease on endogenous intragastric urea could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H+ permeability, particularly at pKa values of HCO3- and NH3, and that in extreme circumstances this may result in gastric ulcer formation. PMID- 8513987 TI - Atrial natriuretic peptide in dumping syndrome. AB - The significance of atrial natriuretic peptide (ANP) was investigated in the maintenance of the fluid volume in hypovolemia associated with dumping syndrome following gastric resection. The study was performed on 10 patients who had undergone a Billroth II procedure. Ten age- and sex-matched patients without previous gastric surgery served as control. Each patient underwent an oral glucose challenge. The patients with gastric resection underwent another glucose challenge with intravenous infusion to maintain the fluid volume. All patients with gastric resection showed subjective symptoms of the early dumping syndrome with significant (p < 0.001) increases (initial and maximum rates; mean +/- SD) in heart rate (from 70 +/- 3 to 122 +/- 4 beats/min) and in hematocrit (from 0.40 +/- 0.005 to 0.45 +/- 0.003). The plasma ANP level decreased significantly from 27.24 +/- 5.01 to 15.94 +/- 3.61 fmol/ml (p < 0.01). A significant negative correlation was found between the changes in hematocrit and the changes in plasma ANP level (r = 0.68; p < 0.001). Neither the subjective symptoms characteristic of the early dumping syndrome nor changes in laboratory parameters were noted in the patients during the challenge with infusion. The results show that the hypovolemia in dumping syndrome is associated with a significant decrease in ANP activity. The regulation of ANP release is also affected: apart from the well known stimulating effect of hypervolemia, there exists an inhibition of secretion in volume-depleted states. PMID- 8513986 TI - Effects of enhancement and antagonism of 5-hydroxytryptamine activity on the influence of metoclopramide on gastric emptying. AB - This study examines the influence of the serotonergic system on the effect of metoclopramide on gastric emptying. Six subjects received the following pretreatments before metoclopramide and paracetamol: fluoxetine (5-HT uptake inhibitor); meterogoline (5-HT1 antagonist); pizotifen (5-HT2 antagonist) or methysergide (5-HT1 and 5-HT2 antagonist). One regimen consisted of metoclopramide (5-HT3 antagonist and 5-HT4 agonist) alone. Gastric emptying was measured by the mean cumulative fraction absorbed-time profiles of paracetamol. Methysergide/metoclopramide significantly delayed gastric emptying from 30 min onwards. Metoclopramide with either metergoline or pizotifen did not retard gastric emptying to the same extent, suggesting a greater influence with simultaneous 5-HT1 and 5HT2 blockade. Metoclopramide/fluoxetine caused a significant decrease in the fractional absorption of paracetamol at 5 min when compared to the metoclopramide regimen. It was assumed that the influence of metoclopramide was not optimal at this stage, therefore possibly indicating domination of 5-HT3 over 5-HT4 effects, resulting in gastric delay. It therefore seems as if all the 5-HT receptors present in the gut have a role to play in the control of gastric emptying. PMID- 8513988 TI - Hyperglycemia reduces gastric secretory and plasma pancreatic polypeptide responses to modified sham feeding in humans. AB - We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 +/- 1.0 mmol/h) was not significantly different from euglycemia (5.4 +/- 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 +/- 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 +/- 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 +/- 95 pmol/l.90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 +/- 71 pmol/l.90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia. PMID- 8513989 TI - Exocrine pancreatic secretion in normal controls and chronic calcifying pancreatitis patients from Burundi: possible dietary influences. AB - Pure pancreatic juice composition was studied, after secretin and cerulein stimulation in 29 people from Burundi (Central Africa): 17 controls and 12 alcoholic chronic pancreatitis (CP) patients. Results were compared to similar data in France. African controls had a similar pancreatic response to hormones apart from a much lower lipase secretion than French controls. In the early non calcified stage of African CP water and bicarbonate secretion were markedly diminished while protein and lipase concentrations were enhanced. In the late stage, secretion was exhausted except that of calcium. Nutritional data were obtained under the same conditions in 40 African controls and in 34 CP patients (including all patients tested for secretion). African controls had a very low fat intake (35.2 +/- 2.6 g/day), and patients had a higher protein and fat intake (144.7 +/- 5.9 and 66.2 +/- 4.8 g/day, respectively) than local controls: as in other countries, CP was associated with a diet enriched in alcohol, fat and protein. PMID- 8513990 TI - Proctitis and proctosigmoiditis--a need to identify the extent of disease in epidemiological surveys. AB - Proctitis and proctosigmoiditis may be distinct clinical entities. The lesions are restricted to the rectum or extend proximally to involve the sigmoid colon, respectively. Barium enema examination should be normal proximal to the rectum and sigmoid colon. Histology is used merely to confirm the disease process. We provide evidence drawn from a large epidemiological database that significantly more patients with proctitis than proctosigmoiditis followed over a mean period of 11 years became asymptomatic or had their diagnosis revised to a non inflammatory bowel disease condition (p < 0.05). The 2 groups were well-matched for age, sex, duration of disease and received similar medical treatment. Future epidemiological studies and therapeutic trials should make a distinction between proctitis and proctosigmoiditis. PMID- 8513991 TI - Occurrence of hepatitis delta virus infection in hepatitis B virus-infected patients with different serum patterns of preS gene-encoded proteins. AB - The occurrence of delta superinfection among viremic and nonviremic HbsAg positive carriers with different serum patterns and levels of preS1 and preS2 antigens was investigated. PreS1 and preS2 antigens in serum, as well as their levels, were found to be independent of hepatitis B virus (HBV) replicative activity. Serological evidence of hepatitis delta virus (HDV) superinfection was found in 34 out of 233 (14.6%) HBsAg-positive carriers; all these 34 patients resulted positive for antibody to hepatitis B 'e' antigen, and 33 of them were negative for circulating HBV-DNA. Delta superinfection occurred only among HBsAg positive carriers whose sera were reactive for both preS1 and preS2 antigens (30 out of 142; 21.1%) or at least for preS1 alone (4 out of 63; 6.3%), but not among the patients with undetectable levels of both these antigens. Serum levels of both preS1 (p < 0.005) and preS2 (p < 0.001) antigens were found to be significantly higher in delta-positive HBsAg-positive carriers than in patients with HBV infection uncomplicated by HDV. In addition to confirm previous observations that the detection of both preS antigens in HBsAg-positive sera is independent of HBV replication, these findings clearly show that HDV infection requires not only the presence of HBsAg, but also the presence of preS peptides, and seem to suggest a low susceptibility of HBsAg-positive carriers with low or undetectable synthesis and secretion of HBV surface proteins to delta superinfection. PMID- 8513992 TI - Journal club issues addressed. PMID- 8513993 TI - Family medicine education in the Third World: struggles and successes. PMID- 8513994 TI - Family APGAR analyzed. PMID- 8513995 TI - The health care research challenge of 1993. PMID- 8513996 TI - Commentary from the Residency Review Committee: the RRC and service-education linkages. PMID- 8513997 TI - Commentary from a residency program director: service-education linkages and the RRC requirements for family practice. PMID- 8513998 TI - Commentary from the National Health Service Corps: service-education linkages and serving the underserved. PMID- 8513999 TI - Balancing service and education: linking community health centers and family practice residency programs. AB - Many medical educators are calling for an increased emphasis on ambulatory care training, but financial constraints are often cited as impediments to developing ambulatory care training sites. A growing number of family practice residency programs (FPRPs) are affiliating with community and migrant health centers (C/MHCs). This movement has the potential to strengthen community-based ambulatory care training, while addressing some of the financial concerns noted above. This article illustrates how FPRPs can establish mutually beneficial linkages with C/MHCs, while operating within the policy parameters established by the Residency Review Committee (RRC) and the Bureau of Health Care Delivery and Assistance (BHCDA). For this to occur, BHCDA and C/MHCs need to calculate the time required for attending physicians to supervise family practice residents and to contribute to the legitimate educational and teaching needs of the FPRP. Conversely, FPRPs must work closely with C/MHCs to ensure that family practice residents maintain acceptable levels of productivity. The RRC can make it more feasible to have pathways at smaller C/MHCs by allowing those attending physicians supervising family practice residents to see a reduced patient load, determined by the number of residents working at the C/MHC. PMID- 8514000 TI - Establishing a linkage between a family practice residency and a local health department. AB - BACKGROUND: Involvement in service-education linkages by family practice residencies is increasing. In the late 1980s, Swedish Hospital Family Practice Residency in Seattle sought to expand into a new site. At the same time, the Seattle-King County Department of Public Health (SKCDPH) identified the Denny Regrade area of Seattle as medically underserved. METHODS: A new clinic was established in the Denny Regrade area through a collaborative effort between Swedish Family Practice Residency and the SKCDPH. The clinic, Downtown Family Medicine, provides the family practice center training for six additional residents, expanding the Swedish Family Practice Residency from 18 to 24 residents. Swedish Hospital finances faculty and residents' salaries and capital equipment at the new clinic, whereas SKCDPH covers ancillary staff and overhead expenses. RESULTS: The new linkage clinic offers a unique educational setting, direct service to medically indigent patients, and shared financing. Problems encountered included cost, control, adequate staffing, and availability of specialty physician services. Through negotiation and flexibility, solutions were found to many of these problems. CONCLUSIONS: The present linkage demonstrates that training residents in a health department setting is a viable option for expanding a residency and providing care to underserved patients. PMID- 8514001 TI - The service-education linkage: implications for family practice residency programs and community and migrant health centers. AB - INTRODUCTION: Access to quality primary health care for our country's underserved populations is a challenge for both the government and physicians. The Division of Medicine, through funding priorities and other initiatives, is encouraging family practice educators to train residents and students for work in community and migrant health centers (C/MHCs) in underserved areas. The objective of this research was to study linkages between family practice residency programs and C/MHCs and determine the reasons for affiliation, disadvantages and advantages, predictors of successful linkages, and common errors in the linkage agreement. METHODS: We conducted in-depth telephone interviews with the directors of 13 of the 19 family practice residency programs identified as having linkages with C/MHCs. RESULTS: All interviewees at residency programs indicated that their programs had a mission to serve underserved patients. The most commonly cited constraining factor cited by both residency programs and C/MHCs was financial support for residents, on-site faculty, and support staff. Many programs reported that residents training at the C/MHC were able to gain a community health perspective and practice community-oriented primary care. Finally, financing the relationship involved many different approaches, ranging from the residency paying all of the salaries, to a sharing of salaries by the residency, state, and/or hospital, to C/MHC paying the salaries either through its own funds or through grant support. DISCUSSION: These data provide an assessment of the current issues that family practice residencies must address to implement service education linkages. They provide an empirical basis to outline the steps involved in forming a linkage between a residency and a C/MHC. PMID- 8514002 TI - A comparison of student clerkship experiences in community practices and residency-based clinics. AB - BACKGROUND: In our required family medicine clerkship, we used data from student logbook records of clinical experience to compare the learning experiences of students in community practices and residency-based clinics. METHODS: Sixty-eight University of Washington students collected data on patients seen during the final two weeks of their family medicine clerkships. We compared patient demographics, location of patient encounters, and clinical problems seen at nine residency and eight community locations in a four-state area. National Ambulatory Medical Care Survey data were used to compare student experiences to national practices. RESULTS: Log data documented that both community practices and residency sites met the course curriculum goals. Some variations occurred between the two types of clerkship sites, however. Students at community practices saw a higher mean number of patients and did more procedures than students at residency sites. Students at residencies were more likely to see patients for health maintenance and pregnancy care and less likely to see lacerations, sprains or strains, and some chronic diseases. CONCLUSION: Episodic log data were successfully used to monitor the objective educational strategies for residency- and community-based student clerkship sites. Although all students met clerkship objectives, there were significant differences in certain aspects of students' clinical experiences at the two types of clerkship sites. PMID- 8514003 TI - A family physician-counselor program for medical students. AB - BACKGROUND: Impairment among medical students has increased over the past decade, thus requiring programs to identify and manage student needs. METHODS: At Eastern Virginia Medical School, first-year medical students are assigned personal physician-counselors from the Department of Family and Community Medicine. These physicians provide health care and assist students in identifying and managing new or preexisting medical and psychosocial problems. Students meet with their physician-counselors during the first week of school to develop rapport and to complete a screening history and genogram. Subsequent small group meetings help students adjust to life in medical school. RESULTS: Psychosocial problems such as alcoholism, mental illness, substance addiction, and sexual abuse have been identified among students and/or their families, and management strategies have been initiated. This program has been evaluated highly by both faculty and students. CONCLUSIONS: This program has been helpful in identifying problems and implementing treatment strategies for medical students. PMID- 8514005 TI - Levels of physician involvement with psychosocial concerns of individual patients: a developmental model. AB - BACKGROUND: Physician involvement in patients' psychosocial concerns is seen as desirable by practicing physicians and family medicine educators. Although the effectiveness of several approaches to psychosocial problems has been demonstrated, the skills required of the physician vary widely. We present a five level developmental model of physician skills in addressing the psychosocial concerns of individual patients. METHODS: To validate the model, 171 outpatient office visits in a residency program were videotaped and rated according to the levels. The inter-rater agreement was 88%. RESULTS: Interviews with lower levels of psychosocial involvement occurred much more frequently than interviews rated at higher levels (48%, 34%, 16%, 2%, 0%, respectively). Involvement at each higher level added approximately two minutes to the length of the visit. The development of higher levels of physician involvement between the first and third year of residency training was not found in this sample. CONCLUSIONS: These results support the validity of the five-level sequence regarding the depth of physician involvement. Because the hierarchy can be used to reliably assess the degree of physician involvement with the psychosocial concerns of individual patients, the model offers potential applications for resident education and further research on the physician-patient relationship. PMID- 8514004 TI - Migraine in family practice: prevalence and influence of sex hormonal status. AB - BACKGROUND: The objective of this study was to determine the prevalence of migraine headache in a family practice patient population. In addition, this study evaluated the simultaneous presence of Raynaud's phenomenon (RP) and migraine and examined the influence of sex hormonal status on migraine symptoms. METHODS: Data from the Continuous Morbidity Registration Project (CMR) of Nijmegen, the Netherlands, were used to identify all patients in the registration who had migraine headache and a comparison group of patients with nonvasospastic tension headache. Questionnaires were used to verify the diagnosis and to determine signs and symptoms of both headaches. RESULTS: There was an average annual prevalence of migraine headache of four per 1,000 men and 16 per 1,000 women. Eighty-five percent of patients diagnosed by family physicians as having migraine were found to fulfill the International Classification of Health Problems in Primary Care (ICHPPC) criteria for migraine headache. Migraine differed from tension headache with regard to the duration of the attacks, concomitant photo- and phonophobia, provoking factors, and the need to use analgesic medications. RP was present in 15% of the migraine group and in 16% of the tension headache group and occurred almost exclusively in women. The headaches were worse during and before menstruation in both groups and improved during pregnancy and menopause in the migraine group to greater extent than in the tension headache group. CONCLUSIONS: The use of the ICHPPC criteria for migraine headache is reliable in morbidity surveys in family practice. Although there was an overlap, migraine differed in various aspects from tension headache. Digital vasospasm and the influence of female hormonal changes were present in both headache groups. PMID- 8514006 TI - Establishing the first family medicine program in Ecuador. AB - The first family medicine residency program in Ecuador was founded in 1987 by a private evangelical mission hospital under the auspices of the Catholic University of Cuenca. Currently, general medicine is an empiric and poorly respected profession, and medical care is fragmented among multiple specialties and competing systems. This paper reviews the basic principles that guided the development of the program and some of the major challenges and difficulties it has faced. The most important principle of this program is the development of family physician role models who work among other health care professionals and contextualize the basic principles of family medicine to fit Ecuadorian society and its medical needs. PMID- 8514007 TI - [Functional state of the cardiovascular system of miners during prolonged adaptation to extreme circumstances]. PMID- 8514008 TI - [Changes in the physical working capacity and blood lipid composition in students over the course of the school year]. PMID- 8514009 TI - [Physiologic standards for local muscle exertion]. PMID- 8514010 TI - [Changes in thermoregulation and external respiration in man during adaptation to cold]. PMID- 8514011 TI - [Short-term memory in people with varying functional mobility of the nervous processes]. PMID- 8514012 TI - [Development of motor skills in the disabled after upper limb amputation]. PMID- 8514013 TI - [Features of endocrine system functioning in natives of northeast Russia. III. Hormonal regulation of reproductive function in Evens]. PMID- 8514014 TI - [Neuroendocrine organization of the mechanism of long-term adaptation in inhabitants of northeast Russia]. PMID- 8514015 TI - [Prevention and control of hypoxic, circulatory and paroxysmal brain disorders: where is the boundary?]. PMID- 8514016 TI - [Effect of noise on interhemispheric relations during human perception of various types of speech information]. PMID- 8514017 TI - [Polyelectroneurographic study of the dynamics of brain processes during acupuncture in people with chronic pain syndrome]. PMID- 8514018 TI - [Changes in cerebral blood flow and respiration during psychoemotional stress]. PMID- 8514019 TI - [Coordinate shift and visual space compression during right hemisphere depression]. PMID- 8514020 TI - [Preference evaluation and autonomic responses during perception of sound intensity]. PMID- 8514021 TI - [EEG structure during performance of voluntary motor tasks]. PMID- 8514022 TI - [Clinico-physiologic aspects of the use of therapeutic electric stimulation of the acoustic nerves in patients with neurosensory hypoacusis]. PMID- 8514023 TI - [Electroencephalographic assessment of the compensatory role of extracerebral veins in patients with brain tumors]. PMID- 8514024 TI - [Structural and cytochemical signs of dysadaptation using blood parameters]. PMID- 8514025 TI - [Changes in oxygen transport properties of blood during various methods of blood oxygenation and blockade of nociceptive impulsation]. PMID- 8514026 TI - [Age-related features of autonomic regulation of cardiac sinus rhythm in health and in disease]. PMID- 8514027 TI - [Physiologic measure of an operator's work in the waiting period and its dependence on the personality traits of the worker]. PMID- 8514028 TI - Rabbit esophageal cells show regulatory volume decrease: ionic basis and effect of pH. AB - BACKGROUND: Regulatory volume decrease (RVD) after osmotic cellular swelling has been shown in several gastrointestinal epithelia but not in esophageal cells. In acid reflux disease, esophageal injury may be related in part to loss of RVD. METHODS: Isolated basal esophageal cells were exposed to an external hyposmolar solution, and changes in relative cell size were assessed using a Coulter counter (Hilaleah, FL) in the presence of K+ and Cl- transport inhibitors and at varying extracellular pH (pHo). RESULTS: At pHo 7.4, a 30% hyposmotic dilution of the external solution caused an initial peak cell swelling (1.15 +/- 0.05-fold) followed by a return to starting cell size by 5 minutes (RVD). RVD was inhibited by Ba2+ (4 mmol/L), quinine (1 mmol/L), or increasing the [K+]o > or = 10 mmol/L. RVD was also inhibited by depleting [Cl-]i or in the presence of 0.5 mmol/L 4,4' diisothiocyanastostilbene-2,2'-disulfonic acid disodium salt (DIDS) or 50 mumol/L diphenylamine-2-carboxylate, a Cl- conductance inhibitor. To test the effect of pH on RVD, cells in solutions at pHo 7.4, 7.0, or 6.8 were subjected to hyposmotic stress; RVD was significantly inhibited at pHo 6.8. This pH-dependent inhibition of RVD was reversed in the presence of valinomycin, a K+ ionophore. CONCLUSIONS: These studies show that isolated esophageal cells possess RVD mechanisms that are mediated by Cl(-)- and pH-dependent K+ effluxes. RVD appears to be inhibited by a decrease in pHo, suggesting the possibility that acid induced esophageal injury results from inhibition of normal volume regulatory mechanisms. PMID- 8514029 TI - Barrett's esophagus: cell cycle abnormalities in advancing stages of neoplastic progression. AB - BACKGROUND: Abnormal proliferation in Barrett's esophagus may predispose to the development of esophageal adenocarcinoma, but previous studies have not determined the specific cell cycle abnormalities that were associated with neoplastic progression. METHODS: Ki67/DNA content multiparameter flow cytometry and DNA content flow cytometry were used to investigate G0, G1, and S phase fractions in advancing stages of neoplastic progression in Barrett's esophagus. RESULTS: In control biopsy specimens from gastric mucosa, G1, S phase, and total Ki67-positive proliferative fractions were low, suggesting that cells were predominantly in G0. Ki67-positive G1 fractions were increased in Barrett's metaplasia. More advanced stages of neoplastic progression were characterized by a subset of biopsy specimens that had aneuploid cell populations, increased S phase fractions, or both. CONCLUSIONS: The development of increased G1 fractions is an early event in Barrett's metaplasia. Increased S phase fractions occur in a subset of specimens typically at more advanced stages of neoplastic progression and often in association with the development of aneuploidy. Neoplastic progression in Barrett's esophagus is associated with at least three types of cell cycle abnormalities: (1) mobilization from G0 into G1; (2) loss of control of the G1/S phase transition; and (3) accumulation in G2. PMID- 8514030 TI - A meta-analysis of cholecystectomy and risk of colorectal cancer. AB - BACKGROUND: Over 60 studies have addressed the hypothesis that the risk of colorectal cancer is increased following cholecystectomy; these studies have yielded inconsistent findings. The aim of the present study was to quantitatively summarize the results from the collective studies. METHODS: A meta-analysis of the published studies addressing the relation between cholecystectomy and colorectal cancer was conducted. RESULTS: The combined results from 33 case control studies showed an association between cholecystectomy and risk of colorectal cancer (pooled relative risk [RR] = 1.34; 95% confidence interval [CI] = 1.14-1.57), particularly when limited to the proximal colon (RR = 1.88; 95% CI = 1.54-2.30). In most studies, the risk was stronger when the first 5-15 years following the surgery were excluded. The results from 6 cohort studies, with follow-up to approximately 15 years postcholecystectomy, were generally null (RR = 0.97; 95% CI = 0.82-1.14). A more limited body of evidence suggests that cholelithiasis is related to an elevated risk of proximal colon cancer. CONCLUSIONS: Because the risks varied substantially by study design and because time since cholecystectomy or potentially confounding factors were often not considered, we could not firmly quantitate this risk. However, the findings are consistent with other evidence that suggests some characteristic of bile acid metabolism increases the risk of cancer of the proximal colon. PMID- 8514031 TI - Cholecystectomy and colorectal cancer. AB - BACKGROUND: An increased risk of large bowel cancer, especially of the right colon, following cholecystectomy has been reported in some studies but contradicted in others. The aim of this study was to settle this question by creating a cohort of cholecystectomy patients that was large enough and with a sufficient follow-up time to detect even weak associations. METHODS: A population based cohort consisting of 62,615 patients who underwent cholecystectomy was followed up for the occurrence of colorectal cancer up to 23 years. RESULTS: There were 633 colorectal cancers versus 637.9 expected (standardized incidence ratio [SIR] = 0.99; 95% confidence interval [CI] = 0.92-1.07). Analyses of an extensive number of subgroups including sex, age at operation, duration of follow up, underlying diagnosis, type of operation, and different cancer sites did not show any association. However, for cancer of the right colon among women, the risk was increased (SIR = 1.24; 95% CI = 1.03-1.48) most prominent 15 years or more after operation (SIR = 1.54; 95% CI = 1.03-2.22). CONCLUSIONS: Overall, there is no excess risk of colorectal cancer following cholecystectomy, but consistent with some earlier reports, we observed an increased risk among women for right-sided colon cancer 15 years or more after operation. PMID- 8514032 TI - Time-dependent changes in enterochromaffin-like cell kinetics in stomach of hypergastrinemic rats. AB - BACKGROUND: Hypergastrinemia has been claimed to cause first hyperplasia and then dysplasia/neoplasia of enterochromaffin-like (ECL) cells in rat stomach. The growth is thought to reflect an accelerated self replication rate of mature ECL cells. The cytokinetics and the histidine decarboxylase (HDC) activity of the ECL cells were investigated during sustained hypergastrinemia. METHODS: Hypergastrinemia was evoked by omeprazole (400 mumol.kg-1 x day-1 orally) for up to 1 year. Immunocytochemistry for histamine was used to determine the ECL cell density and combined with [H3]-thymidine autoradiography to establish the labeling index (LI), i.e., the proportion of the ECL cells that has incorporated [H3]thymidine. RESULTS: The ECL cell density increased progressively for 10-20 weeks in response to the hypergastrinemia and remained at a plateau for the remainder of the study. The hyperplasia was diffuse with additional micronodules at 52 weeks. The ECL cell Ll was maximally elevated after 1-2 weeks and declined to control values after 10-20 weeks of treatment. In contrast, the HDC activity remained elevated for the duration of the study. CONCLUSIONS: The ECL cell hyperplasia reflects the transiently elevated ECL cell Ll during the early phase but is not associated with an accelerated rate of mitosis during the 10-52 weeks period. Even though with time gastrin seems to loose its ability to sustain a high ECL cell Ll it retains its ability to maintain a high HDC activity. PMID- 8514033 TI - Early ductal decompression prevents the progression of biliary pancreatitis: an experimental study in the opossum. AB - BACKGROUND: The value of early endoscopic or surgical interventions to remove bile duct stones and decompress the biliopancreatic ductal system in gallstone pancreatitis is controversial. METHODS: To evaluate this issue, acute hemorrhagic necrotizing pancreatitis was induced in opossums by obstructing the biliopancreatic ductal system with a balloon catheter for 1, 3, or 5 days. RESULTS: A progressive increase in the severity of pancreatitis, as manifested by inflammation, fat necrosis, hemorrhage, acinar cell vacuolization, in vitro lactate dehydrogenase release, and acinar cell necrosis, was noted in these obstructed animals. In contrast, decompression of the obstructed ductal system by removal of the balloon catheter after 1 or 3 days prevented the increase in severity of these parameters of pancreatic injury. CONCLUSIONS: We concluded that the severity of biliary pancreatitis in this model is dependent upon the duration of ductal obstruction and that decompression of the ductal system can prevent progression of the disease. These observations support the practice of early attempts to remove obstructing stones in clinical gallstone pancreatitis. PMID- 8514034 TI - Renal sodium retention during upright posture in preascitic cirrhosis. AB - BACKGROUND: Renal sodium handling in preascitic cirrhosis is not clearly defined. This issue was addressed by evaluating renal sodium metabolism with different postures. METHODS: Renal function and plasma atrial natriuretic factor (ANF), aldosterone, and norepinephrine levels were determined after 2 hours of standing and 30, 60, and 120 minutes after taking up the supine position in 10 patients and 10 healthy subjects. RESULTS: When upright, patients' glomerular filtration rate and plasma ANF and norepinephrine levels did not differ from those of controls. Conversely, renal sodium excretion was reduced. Plasma aldosterone levels, which were slightly elevated, inversely correlated with renal sodium excretion. In the supine position, natriuresis increased by 308% +/- 99% in patients and 113% +/- 29% in controls (P = 0.016), so that it no longer differed between the two groups. Plasma norepinephrine and aldosterone levels decreased to a similar extent in controls and cirrhotics, whereas the increase in plasma ANF level was greater in patients. The changes in natriuresis correlated with those in plasma ANF levels and plasma aldosterone-ANF ratios in both controls and patients. CONCLUSIONS: Aldosterone-dependent sodium retention develops in preascitic cirrhosis during standing. The supine position is the means whereby standing-induced sodium retention can be balanced. PMID- 8514035 TI - Peritoneovenous shunting restores atrial natriuretic factor responsiveness in refractory hepatic ascites. AB - BACKGROUND: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive, antinatriuretic forces such as the renin aldosterone angiotensin system and the sympathetic nervous system, and vasodilatory, natriuretic agents such as atrial natriuretic factor (ANF). Patients with diuretic resistant refractory ascites may require peritoneovenous shunting (PVS) to control ascites. METHODS: To study the factors responsible for the improvement in sodium homeostasis post-PVS, we compared the response to ANF infusion before and 1 month after PVS in 6 patients with massive ascites. RESULTS: Before PVS, sodium excretion at baseline and in response to ANF infusion was blunted but became more normal post-PVS. ANF infusion post-PVS induced a significant increase in the glomerular filtration rate and filtration fraction and also in distal delivery of sodium. ANF's distal effect of increasing the fractional excretion of distally delivered sodium was present pre-PVS and was not significantly increased post-PVS. Changes in sodium handling were accompanied by a significant decrease in antinatriuretic forces (baseline aldosterone, 2079 +/- 507 vs. 647 +/- 17 nmol/L; P < 0.04) post-PVS. CONCLUSIONS: The improvement in sodium homeostasis and response to ANF infusion post-PVS appears to be associated with the decrease in antinatriuretic forces with the loss of massive refractory ascites. Thus, PVS restores the balance toward ANF responsiveness. PMID- 8514036 TI - A physiological role of peptide YY on exocrine pancreatic secretion in rats. AB - BACKGROUND: Peptide YY (PYY) given intravenously was shown to inhibit pancreatic exocrine secretion both in the dog and the rat. However, a possible physiological role of PYY on the pancreatic secretion has not been clarified. The present study was undertaken to investigate its physiological role on the exocrine pancreas. METHODS: In conscious rats, plasma PYY was determined in response to oral ingestion of a 6-mL meal and intravenous infusion of PYY; small intestinal transit time was measured by phenol red as a nonabsorbable marker, and pancreatic secretory studies were performed in rats with pancreatic fistulas and jugular vein catheters. RESULTS: Oral ingestion of the meal (containing phenol red, 1.6 mg/100 mL) significantly increased plasma PYY within 30 minutes. During this period, most (97%) of the phenol red was detected in the proximal two-thirds of the small intestine. Intravenous infusion of PYY in 25, 50, and 100 pmol.kg-1 x h 1 produced a dose-dependent increase in plasma PYY. The dose of PYY that simulated the peak postprandial level was 50 pmol.kg-1 x h-1, and this dose of PYY significantly inhibited the pancreatic secretion stimulated by physiological doses of secretin and cholecystokinin-8 (CCK-8). After the meal, pancreatic secretion of bicarbonate and protein significantly increased in rats pretreated with normal rabbit serum, whereas this increase was significantly augmented in rats pretreated with an anti-PYY serum because the postprandial increase in plasma PYY was abolished. CONCLUSIONS: PYY plays a regulatory role in the postprandial pancreatic exocrine secretion in rats. PMID- 8514037 TI - A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. AB - BACKGROUND: Inherited unconjugated hyperbilirubinemia in Crigler-Najjar type II (CN II) is caused by a strong reduction of bilirubin uridine 5'-diphosphate glucuronosyltransferase (B-UGT) activity. Both B-UGT isoenzymes (B-UGT1 and B UGT2) identified in humans are derived from a single gene by alternative splicing. To clarify the genetic background of CN II and the role of both B-UGT forms in the physiological clearance of bilirubin, we have studied a large kindred with two CN II patients. METHODS: From genomic DNA all B-UGT encoding exons were amplified by polymerase chain reaction and sequenced to identify mutations causing CN II. RESULTS: The CN II patients were found to be homozygous for a nucleotide shift in the unique region of B-UGT1, changing a arginine into a tryptophan, and also for a nucleotide shift in the unique region of B-UGT2, changing a leucine into a valine. Analysis of other family members and of 50 control subjects showed that the mutation in B-UGT1 causes CN II, whereas the mutation in B-UGT2 is a polymorphism. CONCLUSIONS: CN II syndrome appears to be caused by a homozygous mutation in B-UGT1. This indicates that B-UGT1 is the physiological important bilirubin glucuronidating isoform. PMID- 8514038 TI - Chronic endogenous hypergastrinemia in humans: evidence for a mitogenic effect on the colonic mucosa. AB - BACKGROUND: Information concerning the influence that gastrin may exert on the colon is fragmentary and somewhat controversial. This study analyzed the effect of chronic endogenous hypergastrinemia on cell proliferation and tumor occurrence in the human colonic mucosa. METHODS: Twenty-three consecutive hypergastrinemic patients presenting with the Zollinger-Ellison syndrome and 18 normogastrinemic subjects were studied. All had fasting serum gastrin determination, colonoscopy, and cell kinetic measurement in two colonic sites using in vitro 5' bromodeoxyuridine incorporation. RESULTS: Macroscopic tumors, one endocrine and five adenomas, were found in 5 of 23 hypergastrinemic patients, without apparent relationship with the level of gastrin. The labeling indices were significantly higher in hypergastrinemic than in normogastrinemic individuals in the right and left colon, (P < 0.002 to P < 0.001) without resulting in colonic cell hyperplasia. There was no correlation between labeling indices and serum gastrin concentrations or duration of hypergastrinemia. The DNA labeling distribution along the crypt was normal in the two groups, without expansion of the proliferative zone towards the surface. CONCLUSIONS: These results showed for the first time that long-lasting endogenous hypergastrinemia is accompanied by increased in vivo cell proliferation in the human colonic mucosa. However, the prevalence of adenomas (17.4%) in patients, all more than 50 years old, may not be different from that in the general population. PMID- 8514039 TI - Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. AB - BACKGROUND: The aim of the study was to investigate the incidenc, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. METHODS: The study is a follow-up investigation in 234 nonazotemic patients with cirrhosis and ascites. Thirty-nine variables obtained at inclusion were analyzed as possible predictors of hepatorenal syndrome occurrence (Kaplan-Meier method, Mantel-Cox test, and step-wise Cox regression procedure). RESULTS: The probability of hepatorenal syndrome occurrence was 18% at 1 year and 39% at 5 years. Sixteen variables had predictive value for hepatorenal syndrome occurrence in the univariate analysis: history of ascites, hepatomegaly, nutritional status, blood urea nitrogen level, serum creatinine concentration, serum sodium and potassium concentration, serum and urine osmolality, urinary sodium excretion, free water clearance after a water load, glomerular filtration rate, arterial pressure, plasma renin activity, plasma norepinephrine concentration, and esophageal varices. Neither etiology (alcoholic vs. nonalcoholic) nor the Child Pugh score had predictive value. A multivariate analysis disclosed only three independent predictors of hepatorenal syndrome occurrence: low serum sodium concentration, high plasma renin activity, and absence of hepatomegaly. CONCLUSIONS: The hepatorenal syndrome is a relatively frequent complication in cirrhotic patients with ascites that is associated with an extremely short survival. Liver size, plasma renin activity, and serum sodium concentration are predictors of hepatorenal syndrome occurrence in these patients. PMID- 8514040 TI - Increased hepatocyte expression of hepatitis B virus transcription in patients with features of fibrosing cholestatic hepatitis. AB - BACKGROUND: Recurrent hepatitis B after liver transplantation may be complicated by fibrosing cholestatic hepatitis. This syndrome is associated with rapid graft failure and is characterized by ballooning degeneration of hepatocytes and abundant viral antigen expression. METHODS: To study this disorder further, in situ hybridization studies were performed on 36 liver biopsy specimens from 14 transplanted patients with recurrent hepatitis B and 18 nontransplanted controls with chronic hepatitis B. Biopsy specimens were scored for histological features and intensity of riboprobe hybridization signal to hepatitis B virus (HBV) DNA and RNA. RESULTS: HBV DNA hybridization signals of 2+ to 3+ intensity were observed in 53% of the posttransplant biopsies but none of the nontransplanted samples (P < 0.001). HBV RNA signals of this intensity were found in 42% of the transplant biopsy specimens compared with 17% of the nontransplant specimens (P < 0.07). Features of fibrosing cholestatic hepatitis were noted in 12 biopsies; 11 of these displayed RNA signals of 2+ to 3+ intensity (92%) compared with 4 of 24 (17%) biopsy specimens without this diagnosis (P < 0.001). The level of hepatocyte RNA correlated with the extent of hepatocellular ballooning (P < 0.007). CONCLUSIONS: These data suggest that fibrosing cholestatic hepatitis is associated with enhanced hepatitis B virus transcription and support a cytopathic role for the virus in the development of this syndrome. PMID- 8514041 TI - Regulation of extracellular matrix synthesis by transforming growth factor beta 1 in human fat-storing cells. AB - BACKGROUND: Fat storing cells (FSC) are nonparenchymal liver cells generally considered the major source of the hepatic extracellular matrix (ECM). Transforming growth factor beta 1 (TGF-beta 1) is a potent regulator of ECM synthesis in various cell types. In this study, the effect of TGF-beta 1 on procollagen types I, III, IV, laminin (Lam), and fibronectin (FN) synthesis in cultured human FSCs was analyzed. METHODS: FSCs were isolated from wedge sections of normal human livers. Morphological studies were performed by immunofluorescence and electron microscopy. ECM components in human FSC cultures were measured by an enzyme-linked immunosorbent assay. The expression of messenger RNA (mRNA) was evaluated by Northern blot and in situ hybridization. RESULTS: Cultured human FSCs displayed numerous fat droplets in the perinuclear zone, and immunoreactivity for vimentin and alpha-smooth muscle actin. A weak nonfibrillar staining was observed by using a polyclonal antidesmin antibody. TGF beta 1 induced a dose-dependent increase of procollagen I, III, and FN accumulation in human FSC cultures, whereas procollagen IV and Lam production was not affected. Furthermore, TGF-beta 1 increased the expression of alpha 1 (I), alpha 1 (III) procollagen, FN and TGF-beta 1 mRNA in human FSC cultures. CONCLUSIONS: These data indicate that TGF-beta 1 is able to increase the synthesis of procollagen I, III, and FN in cultured human FSCs. Moreover, TGF beta 1 can induce its own mRNA in the same cells. PMID- 8514042 TI - Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275. AB - BACKGROUND: The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury. METHODS: Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue. RESULTS: Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies. CONCLUSIONS: The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD. PMID- 8514043 TI - Prolonged postpartum course of intrahepatic cholestasis of pregnancy. AB - Cholestatic jaundice of pregnancy is generally a self-limiting condition that occurs in the last trimester and disappears within 1-2 weeks after delivery. The cases of two women who developed severe intrahepatic cholestasis of pregnancy are presented. After delivery, pruritus and jaundice increased and the maximal level of bilirubin reached 500 and 433 mumol/L, respectively (normal, < 20 mumol/L). A familial aggregation was present in one case. Extensive laboratory, radiological, and histopathological investigation showed no other cause of jaundice. Cholestyramine, ursodeoxycholic acid, S-adenosylmethionine, evening primrose oil, and ultraviolet light were used without evidence of efficacy. On the other hand, after corticosteroids were given pruritus ceased and biochemical alterations became normal 35 and 43 weeks, respectively, after delivery. During follow-up 2 years after delivery in one patient, symptoms have not recurred and liver function tests have remained normal. A therapy-resistant dry cough in the other patient is described as a new clinical symptom of severe cholestasis. PMID- 8514044 TI - Hepatic fibrin-ring granulomas in giant cell arteritis. AB - Hepatic fibrin-ring granulomas were found in a 70-year-old man with prolonged fever and inflammatory syndrome. Diagnosis of giant cell arteritis was confirmed by temporal artery biopsy. Other diseases usually associated with fibrin-ring granulomas in liver, such as Q fever, cytomegalovirus hepatitis, infectious mononucleosis, Hodgkin's disease, non-Hodgkin's lymphoma, allopurinol treatment, and visceral leishmaniasis, were ruled out. This report suggests that giant cell arteritis should be considered as an additional cause of hepatic fibrin-ring granulomas. PMID- 8514045 TI - The nomenclature of chronic active hepatitis: an obituary. AB - Use of the terms chronic active hepatitis, chronic persistent hepatitis, and chronic lobular hepatitis should be discontinued in favor of an etiologic terminology. Inflammatory activity and necrosis should be evaluated to grade the severity of the process whereas the degree of fibrosis should be used to determine the stage of the disease. Working groups and consensus meetings are needed to establish a widely acceptable current nomenclature and terminology. Once this has been achieved, introduction of the new names will depend on the support of the committees that compile coding manuals and on reviewers and editors of medical journals. PMID- 8514046 TI - Helicobacter pylori: current status. PMID- 8514047 TI - Endoscopic ultrasonography: high technology and cost containment. PMID- 8514048 TI - Cholecystectomy and colorectal cancer. PMID- 8514049 TI - Unveiling the mysteries of inherited disorders of bilirubin glucuronidation. PMID- 8514050 TI - Liver disease in the alcoholic. PMID- 8514051 TI - Acid secretion in human immunodeficiency virus infection. PMID- 8514053 TI - The molecular genetics of colorectal neoplasia. PMID- 8514052 TI - My grandmother's intravenous chicken soup. PMID- 8514054 TI - The intestinal epithelium: a participant in as well as the target of inflammation? PMID- 8514055 TI - Pathogenesis of giardiasis. PMID- 8514056 TI - Prognostic factors in sterile pancreatic necrosis. PMID- 8514057 TI - Alcohol metabolism in healthy subjects. PMID- 8514058 TI - Gastric mucosal hemodynamics in patients with portal hypertensive gastropathy. PMID- 8514059 TI - Endoluminal ultrasonography of the distal esophagus in systemic sclerosis. AB - BACKGROUND: The aim of this study is to apply high-resolution endoluminal sonography (HRES) to the study of the esophageal disease in systemic sclerosis (SSc). METHODS: An HRES transducer was used to image the esophagus. Autopsy specimens of normal and SSc esophagi were imaged to define a hyperechoic abnormality in the normally hypoechoic muscularis propria. The presence or absence of this hyperechoic abnormality of the esophagus in SSc patients was compared with sonographic findings in normal volunteers. The degree of the hyperechoic abnormality was correlated with the results of functional esophageal studies including esophageal motility, lower esophageal sphincter pressure, and 24-hour pH monitoring in SSc patients. RESULTS: A hyperechoic abnormality in the normally hypoechoic muscularis propria on HRES seemed to correspond with the presence of fibrosis on histological sections from the distal esophagus in SSc autopsy specimens. A significant difference was found in the presence of this hyperechoic abnormality in patients with SSc when compared with normal controls (P < 0.001). Finally, there were strong positive correlations between the degree of this hyperechoic abnormality and esophageal manometric abnormalities (r = 0.89; P < 0.001) and supine (r = 0.74; P < 0.01) and total (r = 0.70; P < 0.02) acid reflux on 24-hour pH monitoring. CONCLUSIONS: HRES is a sensitive new method to determine the presence or absence of hyperechoic abnormalities in the muscularis propria and to predict functional abnormalities of the esophagus in patients with SSc. PMID- 8514060 TI - High levels of interleukin 6 and its secondary mediators in spontaneous bacterial peritonitis. PMID- 8514061 TI - An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. AB - BACKGROUND: Surveying vs. performing resection in patients with high-grade dysplasia in Barrett's esophagus is debated because of concern about the accuracy of endoscopic biopsy diagnosis. The aim of this study was to investigate the accuracy of an endoscopic biopsy protocol in patients with neoplastic abnormalities in Barrett's epithelium without obvious esophageal cancer. METHODS: Preoperative and postoperative diagnoses in 28 patients who underwent surgery for high-grade dysplasia or early adenocarcinoma in Barrett's esophagus and compared them with 22 other patients with high-grade dysplasia who were maintained under prospective endoscopic surveillance. All 50 patients lacked gross lesions to suggest esophageal cancer. The endoscopic protocol involved rigorous, systematic acquisition of multiple, large biopsy samples. RESULTS: Overall, 64% of patients had minimal but distinct endoscopic abnormalities that were targeted for biopsies. High-grade dysplasia alone (7 patients) was differentiated from early adenocarcinoma (19 patients). Two patients with preoperative diagnoses of intramucosal adenocarcinoma had high-grade dysplasia in their resection specimens. CONCLUSIONS: This endoscopic protocol accurately detects and differentiates high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. Patients with high-grade dysplasia alone in Barrett's esophagus detected by such a protocol do not necessarily require surgical resection to rule out an undiagnosed adenocarcinoma; electing for surgery should be based on other clinical considerations. PMID- 8514062 TI - Immunocytochemical heterogeneity of lactase-phlorizin hydrolase in adult lactase deficiency. AB - BACKGROUND: Adult lactase deficiency may result either from diminished synthesis of precursor lactase-phlorizin hydrolase (phenotype I deficiency) or from altered posttranslational processing of the precursor protein (phenotype II). The aim of this study was to compare the location of lactase-phlorizin hydrolase along the crypt-villus axis in control with adult lactase-deficient subjects. METHODS: The immunocytochemical distribution of lactase-phlorizin hydrolase was studied in subjects with adult hypolactasia and in controls with persistent high lactase expression. RESULTS: Duodenal biopsy samples from controls showed increasing intensity of brush border staining from upper crypt to midvillus. Subjects with phenotype I deficiency showed reduced and more patchy reaction product over brush borders. In some, maximal staining was localized over the upper half of the villi. The subject with phenotype II deficiency showed patchy staining but also intracellular accumulations of immunoreactivity within the apex of enterocytes mainly on the upper half of villi. Subsequent immunoelectronmicroscopy showed nearly a fourfold increase in label over the endoplasmic reticulum. CONCLUSIONS: These findings support prior observations of diminished enzyme synthesis in phenotype I lactase deficiency and suggest that the alterations in posttranslational processing in phenotype II deficiency involve a partial block in transport from endoplasmic reticulum to Golgi apparatus. PMID- 8514063 TI - Localization of transforming growth factor beta isoforms in the normal murine small intestine and colon. AB - BACKGROUND: The transforming growth factor beta (TGF-beta) proteins are key regulators of cellular growth and differentiation. Previous studies have shown that TGF-beta 1 is a potent growth inhibitor of cultured jejunal epithelial cells. The reported distribution of TGF-beta 1 messenger RNA (mRNA) expression along the intestinal villus has been controversial. The purpose of the current study is to determine the loci of TGF-beta protein expression in the normal small intestine and colon. METHODS: Intestinal localization of TGF-beta isoform mRNA and protein was examined by Northern blot analysis and immunohistochemistry using isoform specific reagents. RESULTS: TGF-beta 1, TGF-beta 2, and TGF-beta 3 mRNA were found in homogenates from the intact mouse jejunum and colon. The three isoforms colocalized in these tissues. Expression in the small intestinal epithelium was most prominent in cells located on the villus tip, and no staining was detected in the crypt. Occasional lymphocytes in the lamina propria were immunopositive, and all layers of the muscularis were moderately stained. This pattern was seen in all regions of the small intestine. The surface epithelium of the colon was intensely immunopositive, whereas cells in the glands were only weakly stained. CONCLUSIONS: TGF-beta molecules may serve overlapping functions in the intestinal tract, and expression in the epithelium may function to arrest growth of cells emerging from the crypt and induce or maintain the terminally differentiated state. PMID- 8514064 TI - Release of bicarbonate from damaged and restituted gastric mucosa in the cat. AB - BACKGROUND: Gastric mucosal damage leads to luminal alkalinization, but its dependence on mucosal blood flow and acid secretory state of the mucosa is not known. This study examined release of bicarbonate to the gastric lumen and mucosal blood flow in cats after mucosal damage caused by 2 mol/L NaCl and during 90 minutes of epithelial restitution. METHODS: Bicarbonate was calculated from measurements of pH and PCO2 in the luminal perfusate. Mucosal blood flow was measured with microspheres. RESULTS: Luminal bicarbonate increased more than twofold after damage in pharmacologically nontreated, pentagastrin-treated, and omeprazole-treated animals (P < 0.001). Luminal bicarbonate thereafter decreased completely to pre-damage level in pentagastrin-treated, partly in nontreated, but remained elevated in omeprazole-treated animals. Mucosal blood flow increased about 100% 15 minutes after damage (P < 0.001), irrespective of secretory state. Bicarbonate availability (arterial [HCO(3-)] x mucosal blood flow) was significantly related to luminal release of bicarbonate from the newly damaged (P < 0.01) but not from the restituted mucosa. CONCLUSIONS: (1) From the newly damaged mucosa, the luminal release of bicarbonate is related to availability of blood-borne bicarbonate. (2) From acid-stimulated restituted mucosa, the bicarbonate produced by the parietal cells is not released to the lumen, but either consumed within the mucosa by back-diffusing H+ or distributed to the systemic circulation. PMID- 8514065 TI - Transforming growth factor beta regulation of migration in wounded rat intestinal epithelial monolayers. AB - BACKGROUND: In vitro studies have suggested that transforming growth factor beta 1 (TGF-beta 1) plays an important role in the regulation of proliferation of intestinal epithelial cells, effecting strong inhibition of proliferation in intestinal epithelial cell lines. Studies were undertaken to assess its role in repair after injury using an in vitro wounding model. METHODS: Wounds were created in confluent monolayers of the intestinal epithelial cell line of IEC-6. Exogenous TGF-beta 1, conditioned media from wounded IEC-6 cultures, or control media were added. Restitution was quantified as the number of cells migrating across the wound edge. Proliferation was assessed by uptake of bromodeoxyuridine and thymidine incorporation. RESULTS: Although TGF-beta was a potent inhibitor of proliferation, it promoted rapid "healing" of the monolayers through stimulation of migration of cells across the wound margin. The physiological importance of this activity was supported by the demonstration that conditioned medium from IEC 6 cells stimulated repair of the wounded monolayers. Effects of the conditioned medium could be entirely blocked by immunoneutralizing anti-TGF-beta antisera. Further, addition of protease inhibitors (aprotinin, epsilon-aminocaproic acid) that prevented the bioactivation of latent TGF-beta secreted by the IEC-6 cells also ablated the effect of the conditioned medium. In addition, expression of TGF beta 1 messenger RNA was significantly enhanced in the wounded monolayers. CONCLUSIONS: These findings suggest that TGF-beta may play an important role in reconstitution of epithelial integrity after mucosal injury. PMID- 8514066 TI - The non-bleeding visible vessel versus the sentinel clot: natural history and risk of rebleeding. AB - Non-bleeding visible vessel and sentinel clot are terms used interchangeably to describe protuberances in the base of ulcers that have recently bled, but a consensus as to their definition or natural history does not exist. In patients with severe ulcer hemorrhage, non-bleeding protuberances were classified as vessels, with or without a small attached clot, or as sentinel clots, according to a schema based on the appearance of the protuberance at endoscopy but not subjected to pathologic correlation. Endoscopic therapy was not performed at the index endoscopic evaluation, and natural evolution was prospectively documented with daily videoendoscopy. Eleven (46%) of 24 patients with non-bleeding protuberances had rebleeding. Independent classification by three authors concurred in 18 (75%) of 24 lesions. Ten (91%) of 11 vessels with or without attached clot rebled versus 0 (0%) of 7 sentinel clots and 1 (17%) of 6 lesions without unanimous classification (p < 0.01, vessels versus other groups). Rebleeding occurred in 5 (71%) of 7 nonpigmented (pale or white), 6 (38%) of 16 red or purple, and 0 (0%) of 1 black protuberances. In general, vessels persisted until rebleeding, whereas sentinel clots disappeared within 1 to 3 days. We conclude that nonbleeding protuberances in ulcer bases can be separated into vessels, which have a high risk of rebleeding, and sentinel clots, which have a low risk of rebleeding. PMID- 8514067 TI - Endoscopy of the pancreatic duct: value of different endoscope types. AB - Diagnostic pancreatoscopy was performed in 38 patients with suspected lesions by means of an endoscopic retrograde approach using two different endoscope types. A 3.1-mm endoscope, which required sphincterotomy, and an 0.8-mm ultra-thin pancreatoscope, which could be passed through a standard catheter into the pancreatic duct, were used. Both endoscope types were effective in detecting and differentiating pancreatic lesions. The advantage of the 3.1-mm pancreatosope is its ability to take biopsy specimens, thus allowing histologic verification of observations. The ultra-thin endoscope may play a role in the initial duct examination. PMID- 8514068 TI - Clinical application of an ultra-thin pancreatoscope using a sequential video converter. AB - The main pancreatic duct was studied endoscopically by inserting an ultra-thin pancreatoscope into the normal papilla of Vater. Recently, we developed a new pancreatoscope system and improved the image, the durability, and the ease of use. A special video converter was connected to the head of the pancreatoscope. The sequential electronic endoscope images were observed on a TV monitor. We performed examinations with this new system in 52 cases (8 with pancreatic cancer, 19 with chronic pancreatitis and 25 normal cases). We studied the brightness, color and quality of the images on 35-mm film and on videotape. As a result, it has become clear that the images obtained with this system are much better than those obtained by the conventional method. Although further improvement in the ability to angulate the endoscope is necessary, this new pancreatoscope system should help diagnose diseases of the pancreas. PMID- 8514069 TI - Carcinoid tumors of the gastrointestinal tract: evaluation with endoscopic ultrasonography. AB - To evaluate the usefulness of endoscopic ultrasonography for carcinoid tumors, we examined 29 patients with gastrointestinal carcinoid tumors (5 gastric, 7 duodenal, and 17 rectal). The smallest size detectable by endoscopic ultrasonography was 2 mm in diameter histologically. The cross-sectional image of the tumors was primarily oval to round. The internal echo was generally hypoechoic and homogeneous. The margins were clearly visualized, and the contour was somewhat smooth. The tumors were mainly located in the third layer. The second layer covered the tumor with the third layer at its base, and it abutted the tumor and became indistinct near its upper interface. These findings were especially recognized in lesions with submucosal invasion and were similar at all sites. The overall accuracy of determining the depth of invasion using endoscopic ultrasonography was 75% (27 of 36 lesions). Limited to the lesions detectable by endoscopic ultrasonography, the accuracy was 90%. Endoscopic ultrasonography was useful in determining the presence of local metastases. Moreover, endoscopic ultrasonography allowed direct detection of perigastrointestinal lymph node metastases (75%, three of four patients). In conclusion, endoscopic ultrasonography was found to be useful for the staging of gastrointestinal carcinoid tumors by determining depth of involvement and presence of perigastrointestinal lymph node metastases. PMID- 8514070 TI - Topical anesthesia with 50 mg of lidocaine spray facilitates upper gastrointestinal endoscopy. AB - To investigate the value of 50 mg of topical lidocaine spray in upper gastrointestinal endoscopy, a randomized double-blind placebo-controlled study was undertaken with 50 mg of lidocaine spray as the active treatment. All patients were sedated with diazepam after administration of the spray. Included in the study were 158 consecutive patients aged 18 years or older being treated at the endoscopy unit of Scunthorpe district general hospital. Tolerance to upper gastrointestinal endoscopy as assessed by endoscopists and patients was evaluated. Of the 158 patients, 85 received the placebo spray and 73 the lidocaine spray. Patient acceptability for upper gastrointestinal endoscopy was significantly greater in the lidocaine group than in the placebo group (p = 0.001), and tolerance to the procedure as assessed by the endoscopist was also significantly greater in the lidocaine group than in the placebo group (p = 0.008). We conclude that topical anesthesia with 50 mg of lidocaine spray facilitates upper gastrointestinal endoscopy for the endoscopist and increases patient tolerance for the procedure. PMID- 8514071 TI - Risk factors associated with vasovagal reactions during colonoscopy. AB - To define the syndrome of vasovagal reactions that occur during colonoscopy and to identify those risk factors associated with this development, we prospectively evaluated patients undergoing colonoscopy with monitored sedation. A total of 223 consecutive patients were evaluated during the 60-day study period. A vasovagal reaction was defined as the occurrence of one or more of the following: diaphoresis, sustained bradycardia of less than 60 beats/min or a decrease in heart rate of 10%, or hypotension (systolic blood pressure less than 90 mm Hg, diastolic blood pressure less than 60 mm Hg, or a reduction in blood pressure of more than 10% below a baseline measurement before colonoscopy and after sedation). Thirty-seven (16.5%) of the 223 patients experienced a vasovagal reaction by our criteria. The remaining 186 patients did not; 100 of these patients were randomly selected by computer to form a control group. No statistically significant differences were observed between the vasovagal and control groups with regard to demographics, cardiopulmonary disease, cardiac medications, procedure success, the endoscopist, patient procedure tolerance, colon preparation, or procedure difficulty. A significant difference was seen in the mean dose of midazolam used in the vasovagal group as compared with that used in the control group (4.6 mg versus 3.9 mg, p < 0.04), and moderate to severe diverticulosis was more commonly seen in the vasovagal group as compared with the control group (43% versus 16%, p < 0.02). Thirteen (35%) of the 37 patients who had a vasovagal reaction required medical intervention (5.8% of the 223 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514072 TI - Oxygen desaturation and cardiac arrhythmias in children during esophagogastroduodenoscopy using conscious sedation. AB - To determine whether oxygen desaturation and cardiac arrhythmias occur in children during esophagogastroduodenoscopy with the use of conscious sedation, we prospectively studied 34 consecutive patients between the ages of 2 months and 18 years. Patients with pulmonary, cardiac, and neurologic disorders were defined as high risk and those without were defined as normal. All patients received intravenous sedation with meperidine, diazepam, or midazolam, used alone or in combination. Pulse oximetry, respiratory rate, and lead II electrocardiogram were recorded throughout all episodes of desaturation and tachycardia. Oxygen desaturation to less than 90% occurred in 68% of normal patients and in 58% of high-risk patients during esophagogastroduodenoscopy. Seventy-five percent of the high-risk patients and 82% of the normal patients had an arrhythmia during esophagogastroduodenoscopy usually associated with oxygen desaturation. Sinus tachycardia was the most common arrhythmia, although other arrhythmias were identified. Despite the frequency of oxygen desaturation and cardiac arrhythmias, no adverse outcome was observed in any patient. Most episodes of oxygen desaturation and cardiac arrhythmia resolved spontaneously. Subdivision of patients into high-risk groups by age, sex, weight, or diameter of endoscope used did not allow prediction of oxygen desaturation or cardiac arrhythmia. Our data suggest that conscious sedation in children undergoing esophagogastroduodenoscopy is safe and free of significant adverse clinical problems. However, conscious sedation during esophagogastroduodenoscopy continues to have certain inherent risks. Therefore we strongly advocate the routine use of continuous cardiac rhythm and pulse oximetry monitoring of all children during esophagogastroduodenoscopy performed with the use of conscious sedation. PMID- 8514073 TI - Venous complications of midazolam versus diazepam. AB - Although some studies have suggested fewer venous complications are associated with midazolam than with diazepam for endoscopic procedures, this variable has not been well documented. We prospectively evaluated the incidence of venous complications after intravenous injection of diazepam or midazolam in 122 consecutive patients undergoing colonoscopy and esophagogastroduodenoscopy. Overall, venous complications were more frequent with diazepam (22 of 62 patients) than with midazolam (4 of 60 patients) (p < 0.001). A palpable venous cord was present in 23% (14 of 62) of patients in the diazepam group, compared with 2% (1 of 60 patients) in the midazolam group (p < 0.002). Pain at the injection site occurred in 35% (22 of 62) of patients in the diazepam group compared with 7% (4 of 60 patients) in the midazolam group (p < 0.001). Swelling and warmth at the injection site were not significantly different between the two groups. Smoking, nonsteroidal anti-inflammatory drug use, intravenous catheter site, dwell time of the needle, alcohol use, and pain during the injection had no effect on the incidence of venous complications. PMID- 8514074 TI - Gastric mucosal blood flow after smoking in healthy human beings assessed by laser Doppler flowmetry. AB - We measured regional gastric mucosal blood flow by laser Doppler flowmetry before and after control (n = 8) or cigarette smoking (n = 8) in healthy human beings. The control group showed no change in both antrum (from 1.15 +/- 0.32 to 1.20 +/- 0.39 V, NS) and corpus gastric mucosal blood flow (from 1.15 +/- 0.32 to 1.12 +/- 0.28 V, NS). In contrast, cigarette smoking caused a significant reduction in gastric mucosal blood flow in the antrum (from 1.08 +/- 0.31 to 0.71 +/- 0.22 V, p < 0.01) and in the corpus (from 0.99 +/- 0.26 to 0.66 +/- 0.24 V, p < 0.01). The magnitude of reduction in gastric mucosal blood flow was similar between the antrum and the corpus (-34% +/- 11% versus -33% +/- 15%, NS). We conclude that cigarette smoking induces a significant reduction in gastric mucosal blood flow and that no heterogeneous response occurs in regional gastric mucosa. In addition, the laser Doppler flowmeter appears to be a sensitive method to assess rapid change in gastric mucosal blood flow in human beings. PMID- 8514075 TI - Development of pleural effusion after sclerotherapy with absolute alcohol. AB - Pleural effusion developed in 6 of 31 patients undergoing esophageal variceal sclerotherapy using absolute alcohol. The effusions were small, appeared within 48 hours of sclerotherapy, and disappeared without treatment within 7 days in all six patients. Prevalence of chest pain was significantly greater when pleural effusions developed than when pleural effusions did not develop (83% of patients versus 19%, respectively, p < 0.05). The persistence of chest pain was also significantly greater when pleural effusions developed than when they did not develop (80% of patients versus 19%, respectively, p < 0.05). We conclude that pleural effusion occurs frequently after esophageal variceal sclerotherapy with alcohol and is commonly associated with chest pain. PMID- 8514076 TI - Laparoscopic observation of liver colored with indocyanine green in chronic hepatitis. I. Improved sensitivity for diagnosis of fibrosis. AB - We investigated the significance of intravenous injection of indocyanine green during laparoscopic examination in chronic hepatitis. The presence or absence of bridging fibrosis was estimated during laparoscopy from the pattern of lobular markings before and after indocyanine green coloration. Laparoscopy without indocyanine green predicted the presence of bridging fibrosis in biopsy specimens with a low sensitivity of 0.42 (specificity, 0.8). After intravenous injection of indocyanine green, lobular markings became clearer and the sensitivity of laparoscopy in the diagnosis of bridging fibrosis was markedly increased (sensitivity, 0.89; specificity, 0.8). These results indicate that the indocyanine green coloration method improves the correspondence between laparoscopy and liver biopsy in evaluating the severity of chronic hepatitis. PMID- 8514077 TI - Laparoscopic observation of liver colored with indocyanine green in chronic hepatitis. II. Correlation with subcapsular ligandin. AB - Intravenous injection of indocyanine green improves the laparoscopic diagnosis of liver disease. To clarify the basis for the laparoscopic appearance of indocyanine green-colored liver, local indocyanine green coloration was compared with the hepatic ligandin in the corresponding subcapsular tissue. Two liver biopsy specimens were obtained from each of 13 patients with chronic hepatitis, and the ligandin was stained by an immunohistochemical method. In cases showing homogeneous indocyanine green coloration, the ligandin in the two biopsy specimens was similarly stained. On the other hand, in cases showing inhomogeneous coloration of indocyanine green, biopsy specimens from the well colored area showed focal regeneration and were rich in ligandin, whereas biopsy specimens from less-colored lesions showed fibrosis, necrosis, or severe inflammation, and the ligandin was poorly stained. These results suggest that the characteristic laparoscopic appearance of the indocyanine green-colored liver reflects the changes of intrahepatic ligandin distribution associated with pathologic changes in the liver of patients with chronic hepatitis. PMID- 8514078 TI - Intraluminal fungal colonization of gastrostomy tubes. AB - Percutaneous endoscopic gastrostomy tubes are frequently colonized with fungal and bacterial organisms. This has not been previously reported. In our sample of 10 patients, nine percutaneous endoscopic gastrostomy tubes were colonized with fungi. This occurred as early as 1 week after placement. Candida tropicalis was isolated in five patients. It is hypothesized that a variety of fungi use components of the gastrostomy tube polymer, such as polymer additives, which contribute to the structural deterioration of the tube. PMID- 8514079 TI - Endoscopic therapy for patients with a post-operative biliary leak. AB - Twenty-three patients with a post-operative biliary leak were treated by various endoscopic methods and results were analyzed. Leaks occurred at the cystic duct in 13 patients, at the common duct in 6 patients, and at an anomalous branch of the right hepatic duct in 4 patients. Treatments included sphincterotomy alone (4 patients), stent alone (6 patients), sphincterotomy and stent (12 patients), and sphincterotomy and nasobiliary drainage catheter (1 patient). Five patients also had supplemental percutaneous catheter drainage of a biloma. All treatments were completed successfully in the absence of major morbidity, and permanent closure of the leak occurred in 100% of cases. Endoscopic therapy for patients with a post-operative biliary leak is safe and effective and should be recommended before surgical re-exploration. PMID- 8514080 TI - The role of polymeric surface smoothness of biliary stents in bacterial adherence, biofilm deposition, and stent occlusion. AB - Bacterial adherence and biofilm deposition onto the surface of polymers used for biliary stents are the initial events that ultimately lead to stent occlusion. Vivathane is a new polymer with an ultrasmooth surface. In this study, stents made from Vivathane were compared to standard plastic stents in an in vitro model. Polyethylene, C-flex, and Vivathane stents were connected in parallel and perfused with infected bile. The surfaces of the polyethylene and C-flex stents developed exuberant bacterial growth and biliary sludge deposition. Vivathane stents were nearly free of bacteria and demonstrated no propensity for biliary sludge deposition. These results indicate that polymeric surface irregularities promote bacterial adherence, biofilm deposition, and accumulation of biliary sludge. The ultrasmooth surface of Vivathane does not allow bacterial adherence and biofilm deposition. Vivathane holds promise as a new polymer for use in biliary stents in long-term applications. PMID- 8514081 TI - Colonoscopic relief of small bowel obstruction. PMID- 8514082 TI - Intraluminal ultrasonography during ERCP with high-frequency ultrasound catheters. PMID- 8514083 TI - Treatment of endoscopic sphincterotomy-induced hemorrhage: injection of bleeding site with ERCP contrast solution using a minor papilla diagnostic catheter. PMID- 8514084 TI - Percutaneous transhepatic management of an impacted endoscopic basket. PMID- 8514085 TI - Acute gastric anisakiasis: observations with endoscopic ultrasonography. PMID- 8514086 TI - Recurrent cholangitis caused by the migration of pancreatic calculi associated with pancreas divisum. PMID- 8514087 TI - Biliary complications of liver transplantation. PMID- 8514088 TI - Refining the prognostic value of endoscopy in patients presenting with bleeding ulcers. PMID- 8514089 TI - Advanced training programs in gastrointestinal endoscopy. PMID- 8514090 TI - Enemas not needed after oral lavage colonoscopy preparation. PMID- 8514091 TI - Portal and gastric mucosal hemodynamics after sclerotherapy. PMID- 8514092 TI - Does gastro-duodenal dyspepsia correlate with (neutrophilic) gastro-duodenitis? PMID- 8514093 TI - Effect of intravenous erythromycin on gastric emptying. PMID- 8514094 TI - Submucosal injection of contrast medium as a radiologic marker for insertion of esophageal prosthesis. PMID- 8514095 TI - Portal vein filling during ERCP. PMID- 8514096 TI - A rectal concretion of hydrocortisone acetate. PMID- 8514097 TI - Spatial clustering of simultaneous nonhereditary gastrointestinal angiodysplasia: small but significant correlation between nonhereditary colonic and upper gastrointestinal angiodysplasia. PMID- 8514098 TI - Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy. PMID- 8514099 TI - [Developments in the therapy of advanced FIGO III ovarian cancer]. AB - From 1982 to 1992 103 patients with ovarian cancer stage FIGO III have been treated. In 38% of the patients there was no residual tumour postoperatively, in 40.8% the residual tumour was smaller than 2 cm. In 51.5% bowel resections were necessary, a stoma was unavoidable in just one case. A lymphadenectomy (pelvic, paraaortic or combined) was done in 46.6% of the patients. Postoperatively, 54.4% of the patients received a platinum-based chemotherapy, in the other patients other kinds of chemotherapy were applied. A radiation of the whole abdomen was done only in 3.9%. A median survival time for more than 60 months could be achieved in tumour-free patients due to the increased radical operations in combination with the platinum based chemotherapy. The lymphadenectomy seems to prolong the survival time of the patients. The positive nodal status is definitely unfavourable for the prognosis. By this therapeutic approach, an increased survival time with a good life quality can be achieved. PMID- 8514100 TI - [The value of etoposide (VP-16) in the therapy of refractory ovarian cancer]. AB - In analogy to Kuhnle et al. (1984) the role of etoposide in patients with cisplatin-refractory ovarian cancer was evaluated. 45 patients were treated with 150-200 mg of etoposide per sa. m. on days 1-3. Acute toxicity was tolerable except alopecia grade III. Remarkable, however, was the induction of two fatal cases of leukaemia following etoposide treatment. The first patient, who was 27 years old, with FIGO stage IIb serous cystadenocarcinoma, which was treated with cisplatin/epirubicin and after a latent period of 45 months, a local recurrence was treated with 8 cycles of etoposide. Twenty-three months after discontinuation of etoposide therapy, the patient showed acute myelogenous leukaemia (AML) of M5b subtype according to the FAB classification. Two days after diagnosis, the patient died of the disease. The second patient, a 55-year old woman with FIGO stage IIa serous cystadenocarcinoma, was treated with cisplatin/cytoxan; 8 cycles of etoposide were given as a second line therapy. This patient, 21 months after discontinuation of etoposide therapy showed a pre-pre-B-acute lymphocytic leukaemia with coexpression of the myeloid antigens. Two months after diagnosis, the patient died of the disease. In 4 out of 38 patients, a complete and in 7 patients a partial remission was induced by etoposide treatment and survival of these responding patients was prolonged in comparison with the nonresponder. The survival was also dependent on CA-125 serum level and the cumulative dose of etoposide administered. Etoposide treatment is an acceptable option as salvage therapy in refractory ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514101 TI - [Adenocarcinoma and adenosis of the vagina. On the histogenesis, diagnosis and therapy of a rare genital neoplasms]. AB - In the United States, vaginal adenosis and clear-cell carcinoma of the vagina were frequently observed in young women, who had been exposed to the synthetic estrogen diethyl-stilbestrol (DES) during their embryonic development. In Germany, obviously, no such exposure occurred. Clearly, such diseases also develop without the context of intrauterine exposure to certain substances. Our own case of such a partly exophytic, partly endophytic adeno-carcinoma of the vagina with multifocal vaginal adenosis, demonstrates the histogenesis, symptoms, diagnostic procedures and therapy of this rare disease. Since young women during their reproductive years are mostly affected, the possibility of fertility conserving surgery is discussed despite the current practice of radical cancer surgery (with and without radiation). In the 25-year-old patient, we conducted a colpectomy whilst leaving the uterus and ovaries, and replaced the vaginal defect by a sigmoid transplant anastomosed to the cervix. The patient has regular menstrual cycles, should, however, not become pregnant for 1 to 2 years for oncological reasons. PMID- 8514102 TI - [Determination of steroid hormone receptors with the biochemical DCC method in endometrial cancer and tumor margin-endometrium relations to cellular changes and hormone level]. AB - In endometrial carcinoma and the surrounding marginal endometrium from 48 postmenopausal patients, the concentrations and dissociation constants of steroid hormone receptors were studied by the dextran-coated charcoal method (DCC), parallel to ploidy and morphology of tumour cell nuclei, grading, and the hormonal status. The results show, that the proportion of receptor-positive tumours is decreased in an advanced stage of disease. The mean receptor concentrations correlate both with nuclei parameters and the morphological results and reflect the process of dedifferentiation in the tumour centre. The higher receptor concentrations, especially the estradiol receptor concentration observed in the marginal endometrium, and the increased estradiol level in serum, demonstrate a raised tendency to proliferation in this region and could support the hypothesis, that a higher receptor level in adenomatous-hyperplastic tissues participates in tumour genesis. In patients with an advanced stage of the disease, determination of both receptors can yield indications for a purposeful adjuvant hormone therapy (anti-estrogen and/or gestagen), in addition to providing an aid to prognosis. PMID- 8514103 TI - [Primary fallopian tube cancer--an Austrian multicenter study]. AB - Incidence and prognostic factors of primary carcinomas of the Fallopian tubes were studied in a retrospective multi-centre analysis of 81 women during the period of 1980 to 1990. Data from 13 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the state-of-the-art of diagnosis and treatment of carcinoma of the Fallopian tubes in Austria, and to compare the results with those from the literature. Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu, Taylor and Hertig. The mean age of the patients was 62.1 years. Thirty-seven (45.7%) tumours were found to be in stage I, sixteen (19.8%) in stage II, nineteen (23.4%) in stage III, and nine (11.1%) tumours in stage IV. In 66 Patients, the tumour could be radically removed. The surgical method applied in 68 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Post-operatively, patients underwent an adjuvant therapy which was either irradiation (n = 32; 39.5%), or chemotherapy (n = 34; 42.0%). Fifteen patients had no therapy after operation. The five-year survival rate for stages I and II was 75% compared to 17% in stages III and IV. PMID- 8514104 TI - [Life expectancy of clinically occult breast cancer. Study of a comparative patient sample since 1975]. AB - We have been observing 2 groups of 50 female patients with occult or clinical breast cancer each of whom was initially treated at the Gynaecologic Hospital of the University of Erlangen-Nurnberg between 1975 and 1978. During the follow-up period, 2 patients out of the group of occult cancer and 13 out of the group of clinical carcinoma died of their primary disease. Four women out of the group of occult cancer and 3 from the group of "clinical carcinoma" have developed recurrences. The differences in survival times according to Kaplan-Meier are immense, even if they are not significant owing to the small number of patients. But it is difficult to obtain and to evaluate larger groups of patients and longer follow-up periods due to the low percentage of occult cancer (7.7 to 10.5% only). There are 30 women out of the group of occult breast cancer living without relapse after an observation period up to 15 years. 27 patients out of the group of "clinical cancer" have not shown any evidence of recurrence up to now. This small difference after such a long follow-up period can be explained by the general life expectancy and by the age at initial treatment. PMID- 8514105 TI - [Photodynamic therapy in patients with recurrent gynecologic cancers]. AB - Patients with recurrent gynaecological carcinomas have a poor prognosis, with a survival of a few months. Three patients with a recurrent vulva carcinoma, one patient with a recurrent cervical carcinoma, one patient with a recurrent endometrial carcinoma, and one patient with a recurrent breast carcinoma underwent PDT after parenteral or topical sensitisation with Photosan 3. From these patients, two of them showed a complete response with no evidence of disease for 32 and 29 months. One patient responded partially with two recurrences, which were treated twice after tropical sensitisation, living now 21 months. The remaining three patients showed partial response and died 3 to 8 months after PDT. The energy applied was derived from an argon-dye-laser ranging between 225 and 750 joule/cm2. Photosan 3 was given intravenously at a dose of 2.5 mg/kg body weight and was tolerated without any allergic reaction. The response rate in three of six patients in recurrent gynaecological malignancies encourages us to pursue PDT in gynaecological disease. PMID- 8514106 TI - [Pressure on the fetal head in vacuum extraction]. AB - The pressure exerted on the foetal head was continuously measured with a specially designed instrument in 4 children delivered by vacuum extraction because of arrested delivery. The results were compared with the values obtained in spontaneous deliveries. Lower head pressure values were found in the vacuum group, with a head pressure to amniotic pressure ratio < 1 (normal > 1) before application of the cup. During extraction the head pressure exceeded the intraamniotic pressure. Normal progress of labour requires not only sufficient intrauterine pressure but also an adequate pressure transmission to the presenting part that must widen the birth canal. A prolonged course of labour may therefore be associated with increased pressure values due to elevated resistance of the birth canal as well as with decreased pressure values due to insufficient transmission of pressure. Hence, the load of the foetal head during uterine contraction cannot be determined from the duration of birth. PMID- 8514107 TI - [Antibody detection after antepartal rhesus prophylaxis: normal values or sensitization]. AB - Antibody screening tests were performed in 29 unsensitized pregnant women after antepartum Rh immune prophylaxis, using the indirect Coombs test (ICT) and a more sensitive ID-microtyping-system (IDM). With the ICT, anti-D antibodies were detected in 85% for at least 4 weeks and at most 8 weeks after immunisation. The maximum titer was 1:8. With the IDM, 97% showed antibodies against 'D' for at least 4 weeks and at most 11 weeks with a maximum of 1:16. The IDM titer was always 1 to 3 steps more sensitive than the ICT. After postpartum Rh immune prophylaxis, anti-D titers were again positive in many of the patients (ICT: 42%; IDM: 60%). In conclusion, it is nearly always possible to measure antibodies against 'D' after antepartum Rh immune prophylaxis and IDM was superior in comparison to ICT. However, maternal isoimmunisation to the rhesus antigen cannot be excluded for sure and patients have then to be controlled. As isoimmunisation could not be confirmed in any of our patients, postpartum Rh immune prophylaxis has to be administered even after detection of an antibody titer against 'D' after antepartum Rh prophylaxis. PMID- 8514108 TI - [Results of extracorporeal membrane oxygenation (ECMO) and perspectives for the asphyctic newborn infant]. AB - Extracorporeal life support with membrane oxygenation (ECMO) has been successfully introduced into the management of asphyctic neonates. Two case studies are given to show the importance of this method in antenatal obstetric management. PMID- 8514109 TI - [In vitro fertilization. Prognostic factors]. AB - Multiple factors influence the outcome of in vitro fertilisation and embryo transfer (IVF-ET). In our prospective study different factors have been subject of examination concerning their effect on the outcome of in vitro fertilisation and embryo transfer. 1237 couples undergoing 1675 consecutive treatment cycles between 1.1.1990-31.12.1991 were included in this study. Prior to treatment, couples were divided into "good" and "poor" prognosis groups. Cycles were prospectively labelled as carrying a potentially "poor prognosis", if one or more of the following factors were noted: 1) female age > 35; 2) an existence of male factor; 3) couples with more than 3 previous unsuccessful treatment cycles. Couples with none of these factors were assigned to the "good" prognosis group. The pregnancy rate per cycle in the "poor" prognosis group was 5.96%, compared with 17.92% per cycle in the "good" prognosis group (p < 0.001). The most important factors determining pregnancy rates were female age and male factor, and we observed that the rate of pregnancy declined after the third treatment cycle. An explanation may be seen in lower fertilisation rates after the age of 35 and cases of poor semen quality. Both will result in poor embryo quality. PMID- 8514110 TI - [Hermaphroditism verus: clinical aspects, diagnosis and therapy in adulthood]. AB - A 20-year old woman, who underwent an intersex operation during infancy, was presented for evaluation of the gonads because of suspected true hermaphroditism. The phenotype was female with regular menstruations. Examination revealed an ovarian tumour of 8 cm on the left side and a normal right ovary. During the operation, the tumour was revealed as an endometriosis cyst, which could be excised whilst preserving the ovarian tissue. The right gonad was an ovotestis. The testicular part was removed because of a 4% risk of malignancy. The different combinations of ovary/testis and ovotestis are described. Diagnosis and therapy of true hermaphroditism should be performed as early as possible to obtain an adequate gonadal function and an undisturbed psychosexual development. PMID- 8514111 TI - [Extension of the concept of extracorporeal fertilization by cryopreservation of impregnated oocytes]. AB - Cryopreservation of human embryos within in-vitro fertilization treatment was already proposed in 1977 by Edwards and Steptoe. Today, this procedure is used worldwide by several teams as a standard method to enhance the success rate of IVF. In spite of this, there are many disadvantages of the freezing of embryos, furthermore it is legally prohibited in Germany. We report on a new concept for treatment, which includes the freezing of impregnated oocytes after IVF and their transfer in subsequent cycles. From 109 out of 120 patients who were treated with a long acting GnRH analogue or a contraceptive pill before IVF stimulation, "supernumerary" impregnated oocytes could be frozen. Twenty-three pregnancies resulted after immediate embryo transfer, and thirty patients, who returned for the transfer of cryopreserved oocytes, became pregnant. Neither the IVF pre treatment, nor the stimulation in the transfer cycles of frozen oocytes with clomiphene citrate, influenced the success rate significantly. Combining the 53 pregnancies, a cumulative pregnancy rate of 49% can be calculated per IVF stimulation treatment. This means a doubling of the success rate, compared with routine IVF treatment. Although there are still problems to be solved, as, for instance, the insufficient implantation rate of 7% after the transfer of frozen/thawed cells, we consider cryopreservation of pronuclear oocytes a useful and promising supplement of IVF treatment. There is no further need for the freezing of embryos. PMID- 8514112 TI - Isolation of stress mutants of Bacillus subtilis by a novel genetic method. AB - A novel genetic procedure is described to identify stress genes in Bacillus subtilis by insertion mutagenesis. In addition, this method allows the rapid mapping of the mutation and the establishment of the DNA sequence of the gene impaired by the mutation. Small restriction fragments of chromosomal DNA of B. subtilis are inserted into a pBR322-based vector, the recombinant plasmids are transformed into B. subtilis, and integrants are selected which arise by recombination between the insert and its homologous region within the bacterial chromosome. About two dozen heat-, cold- and salt-sensitive mutants were isolated. Four mutations were mapped using PBS1 transduction, and the physiology of one salt-sensitive mutant was analysed. PMID- 8514113 TI - Aspartame as a source of essential phenylalanine for the growth of oral anaerobes. AB - Phenylalanine and aspartic acid requirements were determined for 13 species of oral bacteria using the chemically defined medium OMIZ-W1. None of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Eikenella corrodens, Selenomonas sputigena, Treponema pectinovorum, T. socranskii, or Wolinella recta required either of these amino acid constituents of aspartame (L-aspartyl-L-phenylalanine methylester). Phenylalanine was essential for the growth of Capnocytophaga gingivalis, Eubacterium timidum, Fusobacterium nucleatum, Porphyromonas gingivalis, T. denticola, and T. vincentii, while aspartic acid was not required. With the exception of E. timidum, all phenylalanine-dependent strains could grow when the free amino acid was replaced by aspartame at concentrations at least 10 fold lower than those used for aspartame as an artificial sweetener. PMID- 8514114 TI - Rapid, extensive and reversible vacuolation of Schizosaccharomyces pombe induced by amphotericin B. AB - The fission yeast Schizosaccharomyces pombe has no large vacuoles under normal growth conditions, although budding yeasts usually have large central vacuoles. The minimum inhibitory concentration of amphotericin B to S. pombe was 0.5 microgram ml-1; treatment with 0.2 microgram ml-1 for 20 min induced rapid and extensive vacuolation in S. pombe exponential phase cells. Growth rate of the cells with 0.2 microgram ml-1 amphotericin B was much reduced for 6 h, showing extensive vacuolation. Vacuolation in itself was not fatal: on removal of the drug, most cells recovered gradually and eventually multiplied. PMID- 8514115 TI - Antigenic properties of Campylobacter rectus (Wolinella recta) major S-layer proteins. AB - The antigenic properties of the surface layer (S-layer) proteins of various Campylobacter rectus strains including 24 clinical isolates and the type strain ATCC 33238 were examined. S-layer proteins were extracted from whole cells by acid treatment according to the method of McCoy et al. (Infect. Immun. 11, 517 525, 1975). The acid extracts from 23 of the isolates and ATCC 33238 contained two major proteins with molecular masses of 130 kDa and 150 kDa, both of which were identified as subunits of the S-layer after comparison with the protein profiles of acid-treated (S-layer-deficient) cells. An S-layer protein from one isolate (CI-808) demonstrated a different molecular mass (160 kDa). Both the 150 kDa proteins of ATCC 33238 and isolate CI-306 and the 160-kDa protein of CI-808 were purified by ion-exchange chromatography in the presence of urea. In Ouchterlony immunodiffusion experiments with these purified proteins and rabbit antiserum raised to each purified protein, both common and strain-specific antigenic determinants were identified in the C. rectus S-layer proteins. PMID- 8514116 TI - Cloning and extracellular expression in Escherichia coli of xylanases from an alkaliphilic thermophilic Bacillus sp. NCIM 59. AB - A genomic DNA library of an alkaliphilic thermophilic Bacillus was constructed in Escherichia coli with pUC 8 vector and was screened using a Congo red xylan plate clearance assay. Six xylanase positive transformants having identical inserts showed immunological reactivity towards polyclonal antibodies raised against purified xylanase (M(r) 15,800) from the Bacillus. A 4.5-kb HindIII-EcoRI subfragment was found to code for two xylanases of M(r) 14,500 and 35,000. Equivalent amounts of xylanase activity were detected from IPTG induced and noninduced recombinants irrespective of the orientation of the 4.5-kb insert with respect to the lac promoter, indicating that xylanase gene expression was under the control of its own promoter. 95% of the xylanase activity (2 U/ml) was found in the extracellular culture filtrate. The hydrolysis of xylan by the recombinant xylanases yielded mainly xylobiose. PMID- 8514117 TI - Mapping of the ben, ant and cat genes of Pseudomonas aeruginosa and evolutionary relationship of the ben region of P. aeruginosa and P. putida. AB - Genes responsible for the utilization of benzoate, anthranilate or catechol (ben, ant, cat) of Pseudomonas aeruginosa PAO were mapped precisely using a cosmid clone carrying all these genes. Genes were localized either by subcloning and complementation or by Tn5 mutagenesis and mapping of the Tn5 insertions. To achieve this, a novel Tn5 mutagenesis procedure was developed by constructing a Tn5 insertion derivative of the Escherichia coli strain S17-1. Preliminary mapping of the ben cat genes of P. putida PPN was accomplished by complementation using a PPN cosmid bank. Sequence homology was demonstrated by Southern hybridization between the ben regions of both P. aeruginosa and P. putida, implying an evolutionary relationship of this chromosomal region of these two pseudomonads. PMID- 8514118 TI - Utilization of transferrin-bound iron by Listeria monocytogenes. AB - It has been demonstrated that under iron-restricted conditions, Listeria monocytogenes can utilize iron-loaded transferrin (Tf) from a range of species as its sole source of iron for growth. Human transferrin conjugated to horseradish peroxidase (HRP-Tf) bound directly to whole cells of L. monocytogenes. This binding was blocked by apotransferrin indicating that the receptor can bind transferrin in either the iron-bound or iron-free form. Transferrin-binding was not host specific because both bovine and equine transferrin inhibited the binding of HRP-conjugated human transferrin. SDS-PAGE and Western blotting of bacterial surface extracts revealed the presence of a transferrin-binding protein of approximately 126 kDa. PMID- 8514119 TI - Determination of plasmid copy number and stability in Clostridium acetobutylicum ATCC 824. AB - The copy number and stability of several plasmid vectors in Clostridium acetobutylicum ATCC 824 were determined. The protocols were modified from the traditional ones to overcome the problems associated with unusual behavior of C. acetobutylicum cells on solid medium. The plasmid copy numbers of pSYL2, pFNK1, pFNK3, and pFNK5 in strain ATCC 824 were 14, 8, 6, and 6, respectively. pSYL2 and pFNK1 were segregationally stable, since the fractions of plasmid-carrying cells after 60 generations of growth without antibiotic (erythromycin) were 73% and 77%, respectively. Vector pFNK1 carrying fermentative genes was found to be rather unstable. The observed instability seemed to be due to the complex host plasmid interactions by amplified expression of enzymes involved in the tightly regulated primary metabolism of C. acetobutylicum. PMID- 8514120 TI - Diversity in nucleotide acquisition by antigenically similar Chlamydia psittaci of avian origin. AB - Two different nucleic acid precursor utilization patterns were obtained for five avian isolates of Chlamydia psittaci. Three of the isolates behaved in a manner similar to that previously described, showing total dependency on the host cell for ribonucleoside triphosphates and being unable to utilize medium-supplied thymidine. In contrast, the other two isolates were incapable of taking pyrimidine ribonucleotides from the host cell and they could efficiently utilize medium-supplied thymidine. These unusual isolates were resistant to 5 fluorouridine while the other three isolates were sensitive. Of the five isolates only 6BC was sensitive to sulfonamides. The five isolates were divided into two groups by comparing the AluI restriction endonuclease patterns obtained following digestion of the major outer membrane protein (OMP1) gene, amplified by the polymerase chain reaction. The OMP1 genotyping results were confirmed by serotyping. PMID- 8514121 TI - Differences in cell wall polysaccharides of several species of Eupenicillium. AB - A beta-(1-5)-galactofuran was isolated and characterized from fraction F1S (alkali- and water-soluble) of the cell wall of most of the species of Eupenicillium. In E. cryptum, E. euglaucum and E. nepalense the galactan contained galactofuranose with different linkages in addition to beta-(1-5). Fraction F1I (alkali-soluble, water-insoluble) was an alpha-glucan in certain species while in others it was a beta-glucan. Xylose was detected in some species in F1I or in F3 (alkali-soluble at 70 degrees C). The most abundant fraction (F4), resistant to the alkali treatment, was a beta-glucan-chitin complex. Excepting this component, the beta-(1-5)-galactofuran was the polysaccharide which appeared more frequently in the cell wall of species of Eupenicillium and it may have chemotaxonomic relevance. PMID- 8514122 TI - A lipoprotein signal peptide plus a cysteine residue at the amino-terminal end of the periplasmic protein beta-lactamase is sufficient for its lipid modification, processing and membrane localization in Escherichia coli. AB - By genetic exchange and in vitro mutagenesis a hybrid beta-lactamase was constructed that contained the pCloDF13-encoded bacteriocin release protein signal peptide plus a cysteine residue coupled to the mature portion of beta lactamase. Immunoblotting, labelling with [3H]palmitate in the presence and absence of globomycin, and pulse-chase experiments revealed that this hybrid construct is modified with lipid and processed into a lipid-modified beta lactamase. Subcellular localization studies revealed that this hybrid is localized both in the cytoplasmic and outer membranes of Escherichia coli cells. A mutant derivative with an incomplete lipobox (LVG instead of LVAC+1) was not processed and was found in the cytoplasmic membranes. PMID- 8514123 TI - N. I. Vavilov, martyr to genetic truth. PMID- 8514124 TI - Direct cloning of yeast genes from an ordered set of lambda clones in Saccharomyces cerevisiae by recombination in vivo. AB - We describe a technique that facilitates the isolation of yeast genes that are difficult to clone. This technique utilizes a plasmid vector that rescues lambda clones as yeast centromere plasmids. The source of these lambda clones is a set of clones whose location in the yeast genome has been determined by L. Riles et al. in 1993. The Escherichia coli-yeast shuttle plasmid carries URA3, ARS4 and CEN6, and contains DNA fragments from the lambda vector that flank the cloned yeast insert. When yeast is cotransformed with linearized plasmid and lambda clone DNA, Ura+ transformants are obtained by a recombination event between the lambda clone and the plasmid vector that generates an autonomously replicating plasmid containing the cloned yeast DNA sequences. Genes whose genetic map positions are known can easily be identified and recovered in this plasmid by testing only those lambda clones that map to the relevant region of the yeast genome for their ability to complement the mutant phenotype. This technique facilitates the isolation of yeast genes that resist cloning either because (1) they are underrepresented in yeast genomic libraries amplified in E. coli, (2) they provide phenotypes that are too marginal to allow selection of the gene by genetic complementation or (3) they provide phenotypes that are laborious to score. We demonstrate the utility of this technique by isolating three genes, GAL83, SSN2 and MAK7, each of which presents one of these problems for cloning. PMID- 8514126 TI - Stimulation of meiotic recombination in yeast by an ARS element. AB - In a previous study, meiotic recombination events were monitored in the 22-kb LEU2 to CEN3 region of chromosome III of Saccharomyces cerevisiae. One region (the hotspot) was shown to have an enhanced level of both gene conversion events and reciprocal crossovers, whereas a second region (the coldspot) was shown to have a depressed level of both types of recombination events. In this study we have analyzed the effects of a replication origin, ARS307, located about 2 kb centromere proximal to the hotspot region, on the distribution of meiotic recombination events. We find that a deletion of this origin results in a reduction of both gene conversions and reciprocal crossovers in the hotspot region, and that a 200-bp fragment of this ARS element can stimulate both types of recombination events when relocated to the coldspot region. Although the magnitude of stimulation of these events is similar in both orientations, whether the ARS is functional or not, the distribution of events is dependent upon the orientation of the element. PMID- 8514125 TI - Extragenic suppressors of mutations in the cytoplasmic C terminus of SEC63 define five genes in Saccharomyces cerevisiae. AB - Mutations in the SEC63 gene of Saccharomyces cerevisiae affect both nuclear protein localization and translocation of proteins into the endoplasmic reticulum. We now report the isolation of suppressors of sec63-101 (formerly npl1 1), a temperature-sensitive allele of SEC63. Five complementation groups of extragenic mutations, son1-son5 (suppressor of npl1-1), were identified among the recessive suppressors. The son mutations are specific to SEC63, are not bypass suppressors, and are not new alleles of previously identified secretory (SEC61, SEC62, KAR2) or nuclear protein localization genes (NPL3, NPL4, NPL6). son1 mutations show regional specificity of suppression of sec63 alleles. At low temperatures, son1 mutants grow slowly and show partial mislocalization of nuclear antigens. The SON1 gene maps to chromosome IV and encodes a nuclear protein of 531 amino acids that contains two acidic stretches and a putative nuclear localization sequence. We show that son1 mutations suppress sec63-101 by elimination of Son1p function. PMID- 8514127 TI - Molecular and genetic analyses of the B type surface protein gene from Paramecium tetraurelia. AB - The gene encoding the B type variable surface protein from Paramecium tetraurelia stock 51 has been cloned and sequenced. The 7,182 nucleotide open reading frame contains no introns and encodes a cysteine-rich protein that has a periodic structure including three nearly perfect tandem repeats in the central region. Interestingly, the B gene is located near a macronuclear telomere as was shown previously for two other paramecium surface protein genes. In this paper, we characterize four independent mutants with complete macronuclear deletions of the B gene. Previous analysis of different macronuclear deletion mutants of the A surface protein gene demonstrated two types of inheritance: typical Mendelian segregation (as illustrated by d12) and cytoplasmic inheritance (shown by d48). F1 analysis of four B- mutants crossed with wild-type cells reveals heterozygous F1 cell lines derived from both parental cytoplasms contain approximately the same copy number of the B gene, as expected for a recessive Mendelian mutation. Analysis of F2 progeny from three of these four B- mutant crosses indicates that one of the three exhibits a Mendelian 1:1 segregation ratio of B+ and B- cell lines. The other two show a preponderance of B+ cells, but this is not correlated with the parental cytoplasmic type. In addition to having a large number of B+ individuals, the d12.144, A-, B- mutant produced some F2 progeny that stably maintain less than normal macronuclear amounts of the A gene and/or the B gene. PMID- 8514128 TI - Genetic studies of mei-1 gene activity during the transition from meiosis to mitosis in Caenorhabditis elegans. AB - Genetic evidence suggests that the mei-1 locus of Caenorhabditis elegans encodes a maternal product required for female meiosis. However, a dominant gain-of function allele, mei-1(ct46), can support normal meiosis but causes defects in subsequent mitotic spindles. Previously identified intragenic suppressors of ct46 lack functional mei-1 activity; null alleles suppress only in cis but other alleles arise frequently and suppress both in cis and in trans. Using a different screen for suppressors of the dominant ct46 defect, the present study describes another type of intragenic mutation that also arises at high frequency. These latter alleles appear to have reduced meiotic activity and retain a weakened dominant effect. Characterization of these alleles in trans-heterozygous combinations with previously identified mei-1 alleles has enabled us to define more clearly the role of the mei-1 gene product during normal embryogenesis. We propose that a certain level of mei-1 activity is required for meiosis but must be eliminated prior to mitosis. The dominant mutation causes mei-1 activity to function at mitosis; intragenic trans-suppressors act in an antimorphic manner to inactivate multimeric mei-1 complexes. We propose that inactivation of meiosis specific functions may be an essential precondition of mitosis; failure to eliminate such functions may allow ectopic meiotic activity during mitosis and cause embryonic lethality. PMID- 8514129 TI - Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus. AB - We have inserted a yeast nuclear DNA fragment bearing the TRP1 gene and its associated origin of DNA replication, ARS1, into the functional mitochondrial chromosome of a strain carrying a chromosomal trp1 deletion. TRP1 was not phenotypically expressed within the organelle. However, this Trp- strain readily gave rise to respiratory competent Trp+ clones that contained the TRP1/ARS1 fragment, associated with portions of mitochondrial DNA (mtDNA), replicating in their nuclei. Thus the Trp+ clones arose as a result of DNA escaping from mitochondria and migrating to the nucleus. We have isolated 21 nuclear mutants in which the rate of mtDNA escape is increased by screening for increased rates of papillation to Trp+. All 21 mutations were recessive and fell into six complementation groups, termed YME1-YME6. In addition to increasing the rate of mtDNA escape, yme1 mutations also caused a heat-sensitive respiratory deficient phenotype at 37 degrees and a cold-sensitive growth defect on complete glucose medium at 14 degrees. While the other yme mutations had no detectable growth phenotypes, synergistic interactions were observed in two double mutant combinations: a yme1, yme2 double mutant failed to respire at 30 degrees and a yme4, yme6 double mutant failed to respire at all temperatures tested. None of the respiratory defects were caused by loss of functional mtDNA. These findings suggest that yme1, yme2, yme4 and yme6 mutations alter mitochondrial functions and thereby lead to an increased rate of DNA escape from the organelle. PMID- 8514130 TI - Mapping chromosome rearrangement breakpoints to the physical map of Caenorhabditis elegans by fluorescent in situ hybridization. AB - A scheme for rapidly mapping chromosome rearrangements relative to the physical map of Caenorhabditis elegans is described that is based on hybridization patterns of cloned DNA on meiotic nuclei, as visualized by fluorescent in situ hybridization. From the nearly complete physical map, DNA clones, in yeast artificial chromosomes (YACs), spanning the rearrangement breakpoint were selected. The purified YAC DNAs were first amplified by degenerate oligonucleotide-primed polymerase chain reaction, then reamplified to incorporate fluorescein dUTP or rhodamine dUTP. The site of hybridization was visualized directly (without the use of antibodies) on meiotic bivalents. This allows chromosome rearrangements to be mapped readily if the duplicated, deficient or translocated regions do not pair with a normal homologous region, because the site or sites of hybridization of the probe on meiotic prophase nuclei will be spatially distinct. The pattern, or number, of hybridization signals from probes from within, or adjacent to, the rearranged region of the genome can be predicted from the genetic constitution of the strain. Characterization of the physical extent of the genetically mapped rearrangements places genetic landmarks on the physical map, and so provides linkage between the two types of map. PMID- 8514131 TI - A cytogenetic analysis of chromosomal region 31 of Drosophila melanogaster. AB - Cytogenetic region 31 of the second chromosome of Drosophila melanogaster was screened for recessive lethal mutations. One hundred and thirty nine new recessive lethal alleles were isolated that fail to complement Df(2L)J2 (31A 32A). These new alleles, combined with preexisting mutations in the region, define 52 complementation groups, 35 of which have not previously been described. Among the new mutations were alleles of the cdc2 and mfs(2)31 genes. Six new deficiencies were also isolated and characterized identifying 16 deficiency subintervals within region 31. The new deficiencies were used to further localize three loci believed to encode non-histone chromosomal proteins. Suvar(2)1/Su(var)214, a dominant suppressor of position-effect variegation (PEV), maps to 31A-B, while the recessive suppressors of PEV mfs(2)31 and wdl were localized to regions 31E and 31F-32A, respectively. In addition, the cytological position of several mutations that interact with heterochromatin were more precisely defined. PMID- 8514132 TI - Observations on the induction of position effect variegation of euchromatic genes in Drosophila melanogaster. AB - In the T(1;2)dorvar7 translocation, the 1A-2B7-8 segment of the X chromosome is brought to the vicinity of 2R-chromosome heterochromatin resulting in position effect variegation of dor, BR-C and more distal genes, as well as compaction of chromatin in this segment. By irradiation of T(1;2)dorvar7, nine reversions (rev) to a normal phenotype were recovered. In two cases (rev27, rev226), the 1A-2B7-8 section is relocated to the 19A region of the X chromosome, forming free duplications (1A-2B7-8/19A-20F-X-het). Modifiers of position effect do not change the normal expression of the BR-C and dor genes in these duplications. In five reversions (rev3, rev40, rev60, rev167, rev175), free duplications have formed from the 1A-2B7-8 fragment and X chromosome heterochromatin. In these rearrangements, modifiers of position effect (low temperature, removal of Y and 2R-chromosome heterochromatin and a genetic enhancer (E-var(3)201) induce position-effect again. Two reversions (rev45 and rev110) are associated with additional inversions in the original dorvar7 chromosomes. The inversions relocate part of the heterochromatin adjacent to the 1A-2B7-8 section into new positions. In T(1;2)dorrev45, position-effect is seen in the 2B7-8-7A element as compaction spreading from 2B7-8 proximally in some cases as far as the 5D region. Thus, in rev45 the pattern of euchromatin compaction is reciprocal to that of the initial dorvar7 strain. Apparently, it is due to the same variegation-evoking center near the 2R centromere in both cases. In all nine revertants, weakening or complete disappearance of the position-effect is observed despite retention of the 20-kb heterochromatic segment adjacent to the 1A-2B7-8 region. Thus, a 20-kb heterochromatic sequence does not inactivate euchromatin joined to it. PMID- 8514133 TI - Suppression of a lethal trisomic phenotype in Drosophila melanogaster by increased dosage of an unlinked locus. AB - One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and shown that the suppression is a gene dosage effect. Altered dosage of Isis in the presence of two copies of Tpl has no obvious effects. By examining the interactions between Isis dosage and Tpl we suggest that Isis does not directly repress Tpl expression, but acts downstream on the triplo-lethal phenotype of Tpl. PMID- 8514134 TI - The genetic basis of Haldane's rule and the nature of asymmetric hybrid male sterility among Drosophila simulans, Drosophila mauritiana and Drosophila sechellia. AB - Haldane's rule (i.e., the preferential hybrid sterility and inviability of heterogametic sex) has been known for 70 years, but its genetic basis, which is crucial to the understanding of the process of species formation, remains unclear. In the present study, we have investigated the genetic basis of hybrid male sterility using Drosophila simulans, Drosophila mauritiana and Drosophila sechellia. An introgression of D. sechellia Y chromosome into a fairly homogenous background of D. simulans did not show any effect of the introgressed Y on male sterility. The substitution of D. simulans Y chromosome into D. sechellia, and both reciprocal Y chromosome substitutions between D. simulans and D. mauritiana were unsuccessful. Introgressions of cytoplasm between D. simulans and D. mauritiana (or D. sechellia) also did not have any effect on hybrid male sterility. These results rule out the X-Y interaction hypothesis as a general explanation of Haldane's rule in this species group and indicate an involvement of an X-autosome interaction. Models of symmetrical and asymmetrical X-autosome interaction have been developed which explain the Y chromosome substitution results and suggest that evolution of interactions between different genetic elements in the early stages of speciation is more likely to be of an asymmetrical nature. The model of asymmetrical X-autosome interaction also predicts that different sets of interacting genes may be involved in different pairs of related species and can account for the observation that hybrid male sterility in many partially isolated species is often nonreciprocal or unidirectional. PMID- 8514135 TI - Genetics of reproductive isolation in the Drosophila simulans clade: DNA marker assisted mapping and characterization of a hybrid-male sterility gene, Odysseus (Ods). AB - In this study, we address the question of whether there exist major genes that cause complete male sterility in the interspecific hybrids of Drosophila and, if they do, how these genes may be characterized at the molecular level. Our approach is to introgress small segments of the X chromosome from Drosophila mauritiana (or Drosophila sechellia) into Drosophila simulans by repeated backcrosses for more than 20 generations. The introgressions are monitored by both visible mutations and a series of DNA markers. We compare the extent of introgressions that cause male sterility with those that do not. If a major sterility factor exists, there should be a sharp boundary between these two classes of introgressions and their breakpoints should demarcate such a gene. Furthermore, if male sterility is the only major fitness effect associated with the introgression, recombination analysis should yield a pattern predicted by the classical three-point cross. Both the genetic and molecular analyses suggest the presence of a major sterility factor from D. mauritiana, which we named Odysseus (Ods), in the cytological interval of 16D. We thus formalize three criteria for inferring the existence of a major gene within an introgression: (1) complete penetrance of sterility, (2) complementarity in recombination analysis, and (3) physical demarcation. Introgressions of Ods from D. sechellia do not cause sterility. Twenty-two introgressions in our collection have breakpoints in this interval of about 500 kb, making it possible to delineate Ods more precisely for molecular identification. The recombination analysis also reveals the complexity of the introgressed segments--even relatively short ones may contain a second male sterility factor and partial viability genes and may also interfere with crossovers. The spermatogenic defects associated with Ods and/or a second factor were characterized by phase-contrast microscopy. PMID- 8514136 TI - The role of heterochromatin in the expression of a heterochromatic gene, the rolled locus of Drosophila melanogaster. AB - Constitutive heterochromatic regions of chromosomes are those that remain condensed through most or all of the cell cycle. In Drosophila melanogaster, the constitutive heterochromatic regions, located around the centromere, contain a number of gene loci, but at a much lower density than euchromatin. In the autosomal heterochromatin, the gene loci appear to be unique sequence genes interspersed among blocks of highly repeated sequences. Euchromatic genes do not function well when brought into the vicinity of heterochromatin (position-effect variegation). We test the possibility that the blocks of centromeric heterochromatin provide an environment essential for heterochromatic gene function. To assay directly the functional requirement of autosomal heterochromatic genes to reside in heterochromatin, the rolled (rl) gene, which is normally located deep in chromosome 2R heterochromatin, was relocated within small blocks of heterochromatin to a variety of euchromatic positions by successive series of chromosomal rearrangements. The function of the rl gene is severely affected in rearrangements in which the rl gene is isolated in a small block of heterochromatin, and these position effects can be reverted by rearrangements which bring the rl gene closer to any large block of autosomal or X chromosome heterochromatin. There is some evidence that five other 2R heterochromatic genes are also affected among these rearrangements. These findings demonstrate that the heterochromatic genes, in contrast to euchromatic genes whose function is inhibited by relocation to heterochromatin, require proximity to heterochromatin to function properly, and they argue strongly that a major function of the highly repeated satellite DNA, which comprises most of the heterochromatin, is to provide this heterochromatic environment. PMID- 8514137 TI - Stage-specific effects of X-irradiation on yeast meiosis. AB - Previous work has shown that cdc13 causes meiotic arrest of Saccharomyces cerevisiae following DNA replication by a RAD9-dependent mechanism. In the present work, we have further investigated the implicit effects of chromosomal lesions on progression through meiosis by exposing yeast cells to X-irradiation at various times during sporulation. We find that exposure of RAD9 cells to X irradiation early in meiosis prevents sporulation, arresting the cells at a stage prior to premeiotic DNA replication. rad9 meiotic cells are much less responsive to X-irradiation damage, completing sporulation after treatment with doses sufficient to cause arrest of RAD9 strains. These findings thereby reveal a RAD9 dependent checkpoint function in meiosis that is distinct from the G2 arrest previously shown to result from cdc13 dysfunction. Analysis of the spores that continued to be produced by either RAD9 or rad9 cultures that were X-irradiated in later stages of sporulation revealed most spores to be viable, even after exposure to radiation doses sufficient to kill most vegetative cells. This finding demonstrates that the lesions induced by X-irradiation at later times fail to trigger the checkpoint function revealed by cdc13 arrest and suggests that the lesions may be subject to repair by serving as intermediates in the recombination process. Strains mutant for chromosomal synapsis and recombination, and therefore defective in meiotic disjunction, were tested for evidence that X ray-induced lesions might alleviate inviability by promoting recombination. Enhancement of spore viability when spo11 (but not hop 1) diploids were X irradiated during meiosis indicates that induced lesions may partially substitute for SPO11-dependent functions that are required for the initiation of recombination. PMID- 8514138 TI - Drosophila melanogaster male germ line-specific transcripts with autosomal and Y linked genes. AB - We have identified of set of related transcripts expressed in the germ line of male Drosophila melanogaster. Surprisingly, while one of the corresponding genes is autosomal the remainder are located on the Y chromosome. The autosomal locus, at 77F on chromosome arm 3L, corresponds to the previously described transcription unit 18c, located in the first intron of the gene for an RI subunit of cAMP-dependent protein kinase. The Y chromosome copies have been mapped to region h18-h19 on the cytogenetic map of the Y outside of any of the regions required for male fertility. In contrast to D. melanogaster, where Y-linked copies were found in nine different wild-type strains, no Y-linked copies were found in sibling species. Several apparently Y-derived cDNA clones and one Y linked genomic clone have been sequenced. The Y-derived genomic DNA shares the same intron/exon structure as the autosomal copy as well as related flanking sequences suggesting that it transposed to the Y from the autosomal locus. However, this particular Y-linked copy cannot encode a functional polypeptide due to a stop codon at amino acid position 72. Divergence among five different cDNA clones ranges from 1.5 to 6% and includes a large number of third position substitutions. We have not yet obtained a full-length cDNA from a Y-linked gene and therefore cannot conclude that the D. melanogaster Y chromosome contains functional protein-coding genes. The autosomal gene encodes a predicted polypeptide with 45% similarity to histones of the H5 class and more limited similarity to cysteine-rich protamines. This protein may be a distant relative of the histone H1 family perhaps involved in sperm chromatin condensation. PMID- 8514139 TI - An autosomal factor from Drosophila arizonae restores normal spermatogenesis in Drosophila mojavensis males carrying the D. arizonae Y chromosome. AB - Males of Drosophila mojavensis whose Y chromosome is replaced by the Y chromosome of the sibling species Drosophila arizonae are sterile. It is shown that genetic material from the fourth chromosome of D. arizonae is necessary and sufficient, in single dose, to restore fertility in these males. In introgression and mapping experiments this material segregates as a single Mendelian factor (sperm motility factor, SMF). Light and electron microscopy studies of spermatogenesis in D. mojavensis males whose Y chromosome is replaced by introgression with the Y chromosome of D. arizonae (these males are symbolized as mojYa) revealed postmeiotic abnormalities all of which are restored when the SMF of D. arizonae is co-introgressed (these males are symbolized as mojYaSMFa). The number of mature sperm per bundle in mojYaSMFa is slightly less than in pure D. mojavensis and is even smaller in males whose fertility is rescued by introgression of the entire fourth chromosome of D. arizonae. These observations establish an interspecific incompatibility between the Y chromosome and an autosomal factor (or more than one tightly linked factors) that can be useful for the study of the evolution of male hybrid sterility in Drosophila and the genetic control of spermatogenesis. PMID- 8514140 TI - Dating the primigenial C4-CYP21 duplication in primates. AB - C4 and CYP21 are two adjacent, but functionally unrelated genes residing in the middle of the mammalian major histocompatibility complex (Mhc). The C4 gene codes for the fourth component of the complement cascade, whereas the CYP21 gene specifies an enzyme (cytochrome P450c21) of the glucocorticoid and mineralocorticoid pathways. The genes occur frequently in multiple copies on a single chromosome arranged in the order C4 ... CYP21 ... C4 ... CYP21. The unit of duplication (a module) is the C4-CYP21 gene pair. We sequenced the flanking regions of the C4-CYP21 modules and the intermodular regions of the chimpanzee, gorilla, and orangutan, as well as the intermodular region of an Old World monkey, the pigtail macaque. By aligning the sequences, we could identify the duplication breakpoints in these species. The breakpoint turned out to be at exactly the same position as that found previously in humans. The sequences flanking paralogous genes in the same species were found to be more similar to one another than sequences flanking orthologous genes in different species. We interpret these results as indicating that the original (primigenial) duplication occurred before the separation of apes from Old World monkeys more than 23 million years ago. The nature of the sequence at the breakpoint suggests that the duplication occurred by nonhomologous recombination. Since then, the C4-CYP21 haplotypes have been expanding and contracting by homologous crossing over which has homogenized the sequences in each species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514141 TI - Toward an integrated linkage map of common bean. III. Mapping genetic factors controlling host-bacteria interactions. AB - Restriction fragment length polymorphism (RFLP)-based genetic linkage maps allow us to dissect the genetic control of quantitative traits (QT) by locating individual quantitative trait loci (QTLs) on the linkage map and determining their type of gene action and the magnitude of their contribution to the phenotype of the QT. We have performed such an analysis for two traits in common bean, involving interactions between the plant host and bacteria, namely Rhizobium nodule number (NN) and resistance to common bacterial blight (CBB) caused by Xanthomonas campestris pv. phaseoli. Analyses were conducted in the progeny of a cross between BAT93 (fewer nodules; moderately resistant to CBB) and Jalo EEP558 (more nodules; susceptible to CBB). An RFLP-based linkage map for common bean based on 152 markers had previously been derived in the F2 of this cross. Seventy F2-derived F3 families were inoculated in separate greenhouse experiments with Rhizobium tropici strain UMR1899 or X. c. pv. phaseoli isolate isolate W18. Regression and interval mapping analyses were used to identify genomic regions involved in the genetic control of these traits. These two methods identified the same genomic regions for each trait, with a few exceptions. For each trait, at least four putative QTLs were identified, which accounted for approximately 50% and 75% of the phenotypic variation in NN and CBB resistance, respectively. A chromosome region on linkage group D7 carried factor(s) influencing both traits. In all other cases, the putative QTLs affecting NN and CBB were located in different linkage groups or in the same linkage group, but far apart (more than 50 cM). Both BAT93 and Jalo EEP558 contributed alleles associated with higher NN, whereas CBB resistance was always associated with BAT93 alleles. Further investigations are needed to determine whether the QTLs for NN and CBB on linkage group D7 represent linked genes or the same gene with pleiotropic effects. Identification of the QTLs raises the possibility of initiating map-based cloning and marker-assisted selection for these traits. PMID- 8514142 TI - A method of screening for genes of major effect. AB - This paper describes a method for screening animal populations on an index of calculated probabilities of genotype status at an unknown single locus. Animals selected by such a method might then be candidates in test matings and genetic marker analyses for major gene detection. The method relies on phenotypic measures for a continuous trait plus identification of sire and dam. Some missing phenotypes and missing pedigree information are permitted. The method is an iterative two-step procedure, the first step estimates genotype probabilities and the second step estimates genotypic effects by regressing phenotypes on genotype probabilities, modeled as true genotype status plus error. Prior knowledge or choice of major locus-free heritability for the trait of interest is required, plus initial starting estimates of the effect on phenotype of carrying one and two copies of the unknown gene. Gene frequency can be estimated by this method, but it is demonstrated that the consequences of using an incorrect fixed prior for gene frequency are not particularly adverse where true frequency of the allele with major effect is low. Simulations involving deterministic sampling from the normal distribution lead to convergence for estimates of genotype effects at the true values, for a reasonable range of starting values, illustrating that estimation of major gene effects has a rational basis. In the absence of polygenic effects, stochastic simulations of 600 animals in five generations resulted in estimates of genotypic effects close to the true values. However, stochastic simulations involving generation and fitting of both major genotype and animal polygenic effects showed upward bias in estimates of major genotype effects. This can be partially overcome by not using information from relatives when calculating genotype probabilities-a result which suggests a route to a modified method which is unbiased and yet does use this information. PMID- 8514143 TI - Estimation of mitotic stability in conidial fungi: a theoretical framework. AB - Mitotic stability refers to the probability that genetic elements are transmitted to both daughters during mitosis. This is of practical importance in molecular genetics because autonomous cloning vectors should be transmitted at high frequency during mitosis. In filamentous coencytic fungi it is difficult to quantify mitotic stability because a fluctuation test is not feasible. We show how to get around this problem by formulating a general model of the transmission of nuclear genetic elements through the course of conidiogenesis. We derive formulas by two different methods for the expected proportion of conidiospores that retain the element as a function of its mitotic stability and the number of generations of spore production. An important by-product yields the exact probability distributions for the number of conidiospores retaining elements at each stage of conidiophore development. We outline, and illustrate through specific numerical examples, how to use these formulas to estimate mitotic stability. Although we use Aspergillus nidulans as our biological paradigm, the same general framework can be extended to other fungal species, and possibly to less closely related systems as well. PMID- 8514144 TI - F statistics in Drosophila buzzatii: selection, population size and inbreeding. AB - Drosophila buzzatii is confined to reproducing in a well defined patchy environment consisting of rotting cactus cladodes which are ephemeral, permitting at most three generations. Flies emerging from such rots were used to estimate the additive genetic variance within rots and the genetic variance between rots for body size and also were electrophoresed to determine their genotypes at six polymorphic loci. F statistics were estimated from body size and allozyme data. The FST derived from body size was significantly larger than the allozyme FST. It is proposed this is due to selective differentiation of body size. The allozyme FST is used to estimate effective population size: 10 < N < 50. It is suggested that the regularly observed positive FIS's could be due to partial sib mating, S. If so, the estimated lower bound is S = 0.258. Experiments are identified which could support or contradict these interpretations. PMID- 8514145 TI - Maintenance of genetic variability under strong stabilizing selection: a two locus model. AB - We study a two locus model with additive contributions to the phenotype to explore the relationship between stabilizing selection and recombination. We show that if the double heterozygote has the optimum phenotype and the contributions of the loci to the trait are different, then any symmetric stabilizing selection fitness function can maintain genetic variability provided selection is sufficiently strong relative to linkage. We present results of a detailed analysis of the quadratic fitness function which show that selection need not be extremely strong relative to recombination for the polymorphic equilibria to be stable. At these polymorphic equilibria the mean value of the trait, in general, is not equal to the optimum phenotype, there exists a large level of negative linkage disequilibrium which "hides" additive genetic variance, and different equilibria can be stable simultaneously. We analyze dependence of different characteristics of these equilibria on the location of optimum phenotype, on the difference in allelic effect, and on the strength of selection relative to recombination. Our overall result that stabilizing selection does not necessarily eliminate genetic variability is compatible with some experimental results where the lines subject to strong stabilizing selection did not have significant reductions in genetic variability. PMID- 8514146 TI - Using yeast genetics to generate a research environment. AB - Many of the same features of the yeast Saccharomyces cerevisiae that have made it so useful as a genetics and molecular biology research organism make it equally useful as a teaching organism. Furthermore, the fact that it is a modern research organism makes it all the more exciting to students and teachers. The unique characteristic of yeast as a unicellular, eukaryotic organism with a complete sexual life cycle is ideal for teaching. A simple monohybrid cross to explore dominance and recessiveness, a dihybrid cross to demonstrate independent assortment, pigmented adenine auxotrophs for investigating the fundamentals of gene action, and easily measured responses to ultraviolet radiation provide an array of appropriate laboratory tools that put real science in the hands of students and teachers. Direct collaborations between scientists and science teachers bring together complementing knowledge and experience, providing an effective and efficient way to adapt and simplify techniques and procedures to accommodate time and money constraints. Collaborations quickly identify technical and theoretical problems that must be solved for implementation in classrooms. They also provide a continuing stimulus to teachers and students to participate in the research process. PMID- 8514147 TI - Mutations in POL1 increase the mitotic instability of tandem inverted repeats in Saccharomyces cerevisiae. AB - Tandem inverted repeats (TIRs or hairpins) of 30 and 80 base-pair unit lengths are unstable mitotically in yeast (Saccharomyces cerevisiae). TIR instability results from deletions that remove part or all of the presumed hairpin structure from the chromosome. At least one deletion endpoint is always at or near the base of the hairpin, and almost all of the repaired junctions occur within short direct sequence repeats of 4 to 9 base pairs. The frequency of this event, which we call "hairpin excision," is influenced by chromosomal position, length of the inverted repeats, and the distance separating the repeat units; increasing the distance between the inverted repeats as little as 25 base pairs increases their chromosomal stability. The frequency of excision is not affected by representative rad mutations, but is influenced by mutations in certain genes affecting DNA synthesis. In particular, mutations in POL1/CDC17, the gene that encodes the large subunit of DNA polymerase I, increase the frequency of hairpin deletions significantly, implicating this protein in the normal maintainance of genomic TIRs. PMID- 8514148 TI - Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break. AB - In the yeast Saccharomyces cerevisiae, the binding of the Rap1 protein to a site located between the 5' end of the HIS4 gene and the 3' end of BIK1 stimulates meiotic recombination at both flanking loci. By using strains that contain mutations located in HIS4 and BIK1, we found that most recombination events stimulated by the binding of Rap1 involve HIS4 or BIK1, rather than bidirectional events including both loci. The patterns of aberrant segregation indicate that most of the Rap1-stimulated recombination events do not represent the symmetric processing of a double-strand DNA break located at the Rap1-binding site. PMID- 8514149 TI - Instability of a plasmid-borne inverted repeat in Saccharomyces cerevisiae. AB - Inverted repeated DNA sequences are common in both prokaryotes and eukaryotes. We found that a plasmid-borne 94 base-pair inverted repeat (a perfect palindrome of 47 bp) containing a poly GT sequence is unstable in S. cerevisiae, with a minimal deletion frequency of about 10(-4)/mitotic division. Ten independent deletions had identical end points. Sequence analysis indicated that all deletions were the result of a DNA polymerase slippage event (or a recombination event) involving a 5-bp repeat (5' CGACG 3') that flanked the inverted repeat. The deletion rate and the types of deletions were unaffected by the rad52 mutation. Strains with the pms1 mutation had a 10-fold elevated frequency of instability of the inverted repeat. The types of sequence alterations observed in the pms1 background, however, were different than those seen in either the wild-type or rad52 genetic backgrounds. PMID- 8514150 TI - Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. AB - In eucaryotes a cell cycle control called a checkpoint ensures that mitosis occurs only after chromosomes are completely replicated and any damage is repaired. The function of this checkpoint in budding yeast requires the RAD9 gene. Here we examine the role of the RAD9 gene in the arrest of the 12 cell division cycle (cdc) mutants, temperature-sensitive lethal mutants that arrest in specific phases of the cell cycle at a restrictive temperature. We found that in four cdc mutants the cdc rad9 cells failed to arrest after a shift to the restrictive temperature, rather they continued cell division and died rapidly, whereas the cdc RAD cells arrested and remained viable. The cell cycle and genetic phenotypes of the 12 cdc RAD mutants indicate the function of the RAD9 checkpoint is phase-specific and signal-specific. First, the four cdc RAD mutants that required RAD9 each arrested in the late S/G2 phase after a shift to the restrictive temperature when DNA replication was complete or nearly complete, and second, each leaves DNA lesions when the CDC gene product is limiting for cell division. Three of the four CDC genes are known to encode DNA replication enzymes. We found that the RAD17 gene is also essential for the function of the RAD9 checkpoint because it is required for phase-specific arrest of the same four cdc mutants. We also show that both X- or UV-irradiated cells require the RAD9 and RAD17 genes for delay in the G2 phase. Together, these results indicate that the RAD9 checkpoint is apparently activated only by DNA lesions and arrests cell division only in the late S/G2 phase. PMID- 8514152 TI - Direct end labelling of telomeres. AB - A novel approach of direct end labelling of telomeres is presented. Chromosome sized, agarose-embedded DNA was treated with T4 DNA polymerase to remove protruding 3' end of telomeres and to generate single-stranded 5' ends. The DNA was then labelled by the same enzyme in the presence of [alpha-32P]dGTP and cold dATP and dTTP. Labelled yeast chromosomes separated by pulsed field gel electrophoresis maintained their integrity. Digestion of yeast chromosomes separated in pulsed field gels with a restriction nuclease (HinfI), followed by conventional electrophoresis in the second dimension, resulted in a fingerprint like pattern of labelled telomeres. This was very similar to the hybridization pattern of a similar two-dimensional gel probed with cloned yeast telomeric sequence. The same approach enabled us to label telomeres in soybean, determine their size, and to reveal polymorphisms in the length of telomeres between the closely related subspecies Glycine max (soybean) and Glycine soja. PMID- 8514151 TI - Physical maps of the six smallest chromosomes of Saccharomyces cerevisiae at a resolution of 2.6 kilobase pairs. AB - Physical maps of the six smallest chromosomes of Saccharomyces cerevisiae are presented. In order of increasing size, they are chromosomes I, VI, III, IX, V and VIII, comprising 2.49 megabase pairs of DNA. The maps are based on the analysis of an overlapping set of lambda and cosmid clones. Overlaps between adjacent clones were recognized by shared restriction fragments produced by the combined action of EcoRI and HindIII. The average spacing between mapped cleavage sites is 2.6 kb. Five of the six chromosomes were mapped from end to end without discontinuities; a single internal gap remains in the map of chromosome IX. The reported maps span an estimated 97% of the DNA on the six chromosomes; nearly all the missing segments are telomeric. The maps are fully cross-correlated with the previously published SfiI/NotI map of the yeast genome by A. J. Link and M. V. Olson. They have also been cross-correlated with the yeast genetic map at 51 loci. PMID- 8514154 TI - Field performance and heavy metal concentrations of transgenic flue-cured tobacco expressing a mammalian metallothionein-beta-glucuronidase gene fusion. AB - Cadmium (Cd) is a nonessential heavy metal that can cause acute and chronic illness in humans. Some plant species such as tobacco (Nicotiana tabacum L.) tend to accumulate high levels of Cd in leaf tissue, the consumed portion of the plant. Tissue-specific expression of mammalian metallothionein has been suggested as a means of partitioning Cd in nonconsumed portions of transgenic plants. The purpose of the experiment reported here was to evaluate Cd concentration and agronomic performance of four field-grown transgenic tobacco lines harbouring a metallothionein-beta-glucuronidase (MG) gene fusion driven by the constitutive 35S promoter of cauliflower mosaic virus. The trial was grown in a region of Canada known to have high background levels of Cd. The agronomic evaluation showed that some of the transgenic lines were equal to, while others performed more poorly than, the untransformed control for yield, days to flower, and leaf number. Gene expression measured by beta-glucuronidase activity showed that all of the transgenic lines expressed the MG gene in the upper portion of the plant. One line did not express the MG gene in the roots. Cd levels in the leaf tissue of transformed lines were not significantly different from the untransformed control. PMID- 8514153 TI - Identification of short tandemly repeated sequences in extrachromosomal circular DNAs from Drosophila melanogaster embryos. AB - A sequence (scl) belonging to the recently identified dodeca satellite family was found to be a major family of extrachromosomal circular DNA molecules from Drosophila melanogaster embryos. The basic unit consists of the 11-bp repeat 5' ACTGGTCCCGT 3', is 63% G + C rich, and shares some similarity with the Escherichia coli chi sequence. This family accounts for only about 0.06% of the genome but very likely for a higher proportion of the circular DNA molecules. It is organized in the genome into at least five main clusters contained in DNA fragments larger than 20 kb and several minor clusters. These clusters are located in the heterochromatic pericentromeric regions. Two other families of simple repeated sequences, the 1.686 g/cm3 (5' AATAACATAG 3') and the 1.705 g/cm3 (5' AAGAG 3') satellite DNAs, were also found in circular DNAs, while another family, the 1.672 g/cm3 (5' AATAT 3'), was not detected. The representation of the simple repeated sequences in circular molecules is not correlated to their genomic representation. Among the seven families of sequences identified to date in extrachromosomal circular DNAs from embryos, the dodeca satellite, the 240-bp repeat of the rDNA intergenic spacer, and the 1.688 and 1.705 g/cm3 satellite DNAs are the most represented families, while the 5S genes, the histone genes, and the 1.686 g/cm3 satellite DNA are present in a lower amount. PMID- 8514155 TI - Nucleotide sequence and evolutionary conservation of a minisatellite variable number tandem repeat cloned from Atlantic salmon, Salmo salar. AB - We describe the nucleotide sequence, extent of polymorphism, and evolutionary conservation of a minisatellite cloned from a fish, Atlantic salmon (Salmo salar). The Ssal minisatellite contains a 16-bp repeat exhibiting partial sequence identity to bird and mammal minisatellites but most closely resembling an insect minisatellite (81% sequence identity). The Ssal locus exhibits a minimum of three to seven alleles per population in three eastern North American salmon populations. A probe based on the nonrepetitive 5' flank of Ssal detected a polymorphic locus in a variety of salmoid species, suggesting that this locus has persisted in its polymorphic state for > 25 million years. Multiple polymorphic bands detected by the same probe suggest the presence in salmonid genomes of additional minisatellite loci that are related to Ssal either through the tetraploidization of the salmonid genome or some other mechanism of gene duplication. PMID- 8514156 TI - Larger nuclei in the larval brain of Drosophila nasutoides often show underreplication, whereas metaphases provide a reliable DNA standard. AB - Specific nuclear regions are highly condensed as heterochromatin during the postembryonic life-span of dipterans. Somatic nuclei are usually endoreplicated to form polyploid sets of chromosomes or polytene elements, or even a mixture of both. Such genomic redundancy presents the possibility that condensation is superimposed by underreplication. From the very early stages, DNA in heterochromatin may be selectively excluded from endoreplication. The result is underrepresentation of heterochromatic sections (both DNA and heterochromatin associated proteins) relative to euchromatin in endoreplicated nuclei. Drosophila nasutoides possesses a novel karyotype in which chromosome 4 contains most or all of the heterochromatin DNA (62% of the genome). This characteristic makes it easy to follow the fate of chromosome 4 during genome multiplication. Larger cells were found adjacent to neuroblasts and ganglion mother cells in the larval brain. Heterochromatin DNA is underrepresented relative to euchromatin in some 60% of these larger nuclei, while DNA in euchromatin selectively undergoes up to five endoreplications. Underreplication begins in the very first endoreplication, more rarely during the second or the third. The resulting relative diminution of chromosome 4 corresponds with the quantity of nuclear DNA absent from other somatic tissues. Some brain nuclei are not underreplicated and carry out only three complete endoreplications at most. However, in a few nuclei heterochromatin DNA is amplified relative to euchromatin in the same cell. These results are based on data for mitotic metaphases from neuroblasts that were found to be reliable as an endogenous 4C DNA standard. PMID- 8514158 TI - Sequence analysis of cloned human satellite DNAs reveals nonrandom variations. AB - We have cloned, from the genome of HeLa cells, related 1.8-kb highly repetitive EcoRI satellite II (and III) DNA family members that displayed a high degree of TaqI and HinfI variations. Comparative sequence analysis of these cloned DNAs suggests that highly repetitive satellite DNAs may have evolved and diversified from the rapid amplification of a pentameric unit (5' TTCCA 3'), by processes including random and non-random mutations. Base conservation, as well as mutational hotspots, were found associated with these related satellite II and III DNAs. The accumulation of C to G transversions within the pentamers, generating TaqI and HinfI sites, as well as C to T transitions at CpN dinucleotides, appear to be responsible for much of the microheterogeneity observed between related satellite II and III DNA family members. PMID- 8514157 TI - Human chromosome 5 sequence primer amplifies Alu polymorphisms on chromosomes 2 and 17. AB - Members of the Alu family of repetitive elements occur frequently in the human genome and are often polymorphic. Techniques involving Alu element mediated polymerase chain reactions (Alu PCR) allow the isolation of region-specific human DNA fragments from mixed DNA sources. Such fragments are a source of region specific Alu elements useful for the detection of Alu-related polymorphisms. A clone from human chromosome 5, corresponding to locus D5F40S1, was isolated using Alu PCR differential hybridization. Alu elements within this clone were investigated for the presence of potentially polymorphic 3' polyA tails. Primers were devised to amplify the 3' polyA tail of an Alu element present within the clone. One primer, D5F40S1-T, was specific to the DNA flanking the 3' end of the Alu element, and the other primer was homologous to sequences within the element. When these primers were used in PCR reactions, products from chromosomes 2 and 17 (loci D2F40S2 and D17F40S3) were amplified in addition to the expected product from chromosome 5. The most likely explanation for this nonspecific amplification is that the D5F40S1-T primer is located within a low-copy repetitive element that is 3' of the Alu element. This phenomenon presents a potential problem for the identification of region-specific Alu polymorphisms. PMID- 8514159 TI - Genome organization and restriction site map of the mitochondrial DNA of the housefly (Musca domestica). AB - A restriction map of the housefly mitochondrial DNA was constructed. The putative arrangement of the major coding regions was determined by two methods. In the first, Drosophila clones of known gene content were hybridized to housefly restriction fragments on Southern blots. In the second, rare restriction sites and clusters of restriction sites were used to align the housefly restriction map with that of Drosophila yakuba. Both methods produced the same apparent gene arrangement. PMID- 8514160 TI - An overview of allergens. PMID- 8514161 TI - Allergen immunotherapy: definition, indication, and reactions. PMID- 8514162 TI - Skin testing in allergy. PMID- 8514163 TI - Stinging insect allergy and venom immunotherapy. PMID- 8514164 TI - In vitro tests for allergy and immunology. PMID- 8514166 TI - Sinusitis. PMID- 8514165 TI - Allergic rhinitis. PMID- 8514167 TI - Asthma classification. PMID- 8514168 TI - Potentially fatal asthma. PMID- 8514169 TI - Allergic bronchopulmonary aspergillosis. PMID- 8514170 TI - Atopic dermatitis. PMID- 8514171 TI - Urticaria and angioedema. PMID- 8514172 TI - Anaphylaxis. PMID- 8514173 TI - Idiopathic anaphylaxis. PMID- 8514174 TI - Hypersensitivity pneumonitis. PMID- 8514175 TI - Occupational immunologic lung disease. PMID- 8514176 TI - Food allergy. PMID- 8514177 TI - Approach to primary immunodeficiency. PMID- 8514178 TI - Allergy-immunology. Unproved techniques and theories. PMID- 8514179 TI - Spain, Portugal, Christopher Columbus, and the Jewish physician: Part II. PMID- 8514180 TI - Commentary: merger of the Academy and College of Allergy and Immunology. PMID- 8514181 TI - Commentary: merger of the ACAI and the AAAI. PMID- 8514182 TI - Commentary on relationship of SRL allergy societies to AAAI and ACAI. PMID- 8514183 TI - Analysis of the petunia nitrate reductase apoenzyme-encoding gene: a first step for sequence modification analysis. AB - In this paper, we describe the gene (nia) coding for the apoenzyme of the nitrate reductase (NR) of petunia. A full-size genomic clone was isolated from a genomic library, using the tobacco nia2 cDNA as a probe, and sequenced. The open reading frame is interrupted by three introns and encodes a protein of 909 amino acids which reveals between 92% and 68% identity to the NADH NR apoenzyme from other higher plants. Southern analyses indicated that the NR apoenzyme is encoded by a single-copy gene, although another region homologous to part of nia was also identified. The analysis of the steady-state level of nia mRNA showed that the petunia nia is regulated by the nitrogen source and is under the control of the circadian rhythm. PMID- 8514184 TI - Genomic structure and sequence analysis of Drosophila melanogaster HSC70 genes. AB - We report the identification of two new members of the Drosophila melanogaster HSP70 gene family, HSC3 and HSC5. DNA sequence analysis predicts that HSC3 encodes a 72-kDa protein with a hydrophobic leader sequence and a C-terminal retrieval tetrapeptide, KDEL, characteristics associated with luminal endoplasmic reticulum (ER) proteins. Sequence analysis predicts that HSC5 encodes a 74-kDa protein with a characteristic mitochondrial leader sequence. We report the deduced amino acid (aa) sequence for the previously identified gene, HSC1. HSC1 encodes a 70-kDa protein lacking a leader sequence and is presumed to have a cytoplasmic localization. A comparison of the deduced aa sequences of these and hsc70 proteins from different species indicates that hsc70 proteins residing in the same intracellular compartment in different organisms are more similar to each other than are hsc70s from the same organism, but different organelles. PMID- 8514185 TI - Developmental regulation and butyrate-inducible transcription of the Xenopus histone H1(0) promoter. AB - We have isolated genomic clones of the Xenopus laevis histone H1(0) promoter and identified regulatory elements mediating the transcriptional regulation of the H1(0) gene. Expression of H1(0) is associated with the terminal differentiation of many cell types. During X. laevis development, H1(0) mRNA is present in the oocyte and egg, but remains at low levels during embryogenesis until hatching. After this time, mRNA levels accumulate dramatically correlating with the differentiation of many tissue types, e.g., liver and skin. Accumulation of H1(0) mRNA can be induced at earlier development stages by treating embryos with butyrate. The enhanced transcription of H1(0) in adult somatic cells, as well as the butyrate inducibility of the gene, have been investigated using transfection of adult X. laevis A6 somatic cells. We have defined specific protein-nucleic acid interactions with three cis-acting elements. Two previously defined gene regulatory elements: the H1 box, normally involved in the regulation of the H1 gene, and the H4TF2 site, normally involved in the regulation of the H4 gene, appear to have novel roles in determining differentiation-specific H1(0) expression. These two elements act together with a new distal cis-acting element in order to sustain high levels of basal transcription and to potentiate transcription following butyrate treatment. PMID- 8514186 TI - Characterization of Xenopus laevis gamma-crystallin-encoding genes. AB - In order to gain insight into crystallin (Cry)-encoding gene (cry) evolution and developmental function, we have determined the gene structure and sequence of several Xenopus laevis gamma-cry. These encode the most abundant Cry in the embryonic lens. Four of the X. laevis gamma-cry, which are part of a multigene family, were isolated from a X. laevis genomic library and demonstrated to have the same gene structure as gamma-cry from other vertebrates, thereby providing further evidence that the split between beta and gamma members of the beta gamma cry family occurred relatively early in evolution. Sequence comparisons indicate that these X. laevis genes share 88-90% nucleotide sequence identity in the protein coding regions, which is slightly higher than the identity observed between gamma-cry of other species. The 5' upstream regions of X. laevis gamma cry contain a few short stretches of homology and one putative promoter element conserved among all cry genes but lack other regions common to gamma-cry promoters from other organisms. The deduced amino acid sequences of all four genes and one cDNA suggest that the structure of X. laevis gamma-Cry is highly conserved with that of other vertebrate gamma-Cry, as deduced from the known three-dimensional structure of bovine gamma B Cry. PMID- 8514187 TI - Efficient secretion of murine Fab fragments by Escherichia coli is determined by the first constant domain of the heavy chain. AB - Fab fragments of IgG1 and IgG3 subclass antibodies which bind to 2 phenyloxazolone (Ox) were produced in Escherichia coli. The signal sequences of the Fd and L chains were correctly processed, the fragments were secreted into the periplasmic space and released into the culture medium upon prolonged cultivations. The yields of active Ox IgG1 and Ox IgG3 Fab fragments after one step purification from the culture medium by affinity chromatography were 2 micrograms/ml and 0.5 micrograms/ml, respectively. The majority of the purified Ox IgG1 Fab was properly assembled, but in the case of Ox IgG3, the preparation was found to consist of a complete L chain and C-terminally degraded fragments of the Fd chain. A deletion up to the interchain disulfide bond in the first constant domain (CH1) of the Ox IgG3 Fd chain led to proper assembly of the truncated Fab fragment. The production level of the truncated fragment was comparable to that of the Ox IgG1 Fab and its hapten-binding activity similar to that of the idiotype monoclonal antibody. The temperature stability of the Ox IgG1 Fab was similar to that of the intact antibody. However, both of the Ox IgG3 Fab fragments showed reduced stability, suggesting that the CH1 domain contributes significantly to the thermal stability of the Fab fragment. PMID- 8514188 TI - A homopurine:homopyrimidine sequence derived from the rat neuronal cell adhesion molecule-encoding gene alters expression in transient transfections. AB - A 178-bp homopurine-homopyrimidine (R:Y) sequence is located upstream from the transcription start point (tsp) of the rat neuronal cell adhesion molecule encoding gene (NCAM). This R:Y sequence contains several mirror repeats. Such sequences have been proposed to regulate gene expression. To determine its effect on gene transcription, a DNA fragment containing the R:Y sequence was cloned into a luciferase-encoding (luc) expression vector. Transient transfection assays with the R:Y-luc constructs were performed in cell lines which constitutively express (B104 rat neuronal cells and C6 rat glial cells) or lack (H411E rat liver cells and L mouse fibroblast cells) NCAMs. In its natural orientation, the R:Y sequence caused a 2.5-fold reduction in luc expression in B104 and H411E cells, but had a statistically insignificant effect in C6 and L cells. The magnitude of the R:Y sequence reduction in luc expression was position and orientation dependent (varying from 2- to 5.5-fold). To determine if nuclear protein(s) specifically bind the sequence, gel retardation assays of a DNA fragment containing the R:Y sequence were carried out with nuclear extracts from these four cell lines. Specific DNA-protein interaction was found with B104 and H411E nuclear extracts, but not with C6 and L cell nuclear extracts. Competition experiments indicate that the (AGG):(TCC) repeat segment within the rat R:Y sequence may constitute the protein-binding domain. These results indicate that the R:Y sequence may have a negative effect on gene transcription in certain cell lines. In correlation with this negative effect, these same cell lines also contain nuclear proteins which bind the sequence. PMID- 8514189 TI - The human erythropoietin-encoding gene contains a CAAT box, TATA boxes and other transcriptional regulatory elements in its 5' flanking region. AB - We have reported the cloning and expression of a human erythropoietin (hEp) encoding cDNA [Lee-Huang, Proc. Natl. Acad. Sci. USA 81 (1984) 2708-2712]. Using this hEp cDNA as a probe, we isolated a 9.3-kb BamHI genomic Ep clone from a human leukocyte library soon thereafter. The size and restriction map of this clone is in agreement with restriction analysis of human genomic DNA probed with the hEp cDNA, demonstrating that this clone is representative of the single hEp gene. This clone is unique in that it extends beyond any reported hEp genomic clone by 3.9 kb on the 5' side and by 1.8 kb on the 3' side. The promoter function of the newly described 5' flanking region has been demonstrated by the expression of biologically active hEp in transfected cells. We find that, despite reports to the contrary, hEp does contain classic canonical TATA boxes and a CAAT box. The 5'-flanking region also contains cytokine-responsive consensus sequences, tissue-specific and metal-responsive elements, CRE and GRE sites, and binding sites for transcription factors, including AP1, NF-kappa beta and Sp1. These regulatory elements have not been found in the hEp genomic clones thus far reported. The identification of these elements and their precise localization in hEp should be useful in studying the regulation of hEp expression, as well as in gene therapy and physiologic modulation of this hormone. PMID- 8514190 TI - Acorn barnacle Megabalanus rosa lectin (BRA-3): cDNA cloning, gene structure and seasonal changes of mRNA and protein levels. AB - We have isolated cDNA clones coding for a lectin (BRA-3) from the acorn barnacle, Megabalanus rosa. Sequence comparison of the cDNA clones has revealed polymorphism in the BRA-3 mRNA, which results from single-nucleotide (nt) differences at three positions. All three differences are within the coding region and cause conservative amino acid (aa) changes. The BRA-3 gene is composed of four exons, and the three single-nt differences are located on different exons. In addition, the BRA-3 mRNA and BRA-3 protein levels increased during early summer in a similar fashion, indicating that BRA-3 production is regulated mainly at the level of transcription. PMID- 8514191 TI - Expression of chick and yeast beta-tubulin-encoding genes in insect cells. AB - A chick cDNA encoding the beta 2 isotype of tubulin (beta 2Tub) was cloned into a baculovirus expression vector designed to produce unfused proteins, and several recombinant viruses (re-viruses) were isolated. Immunoblotting studies of homogenates of insect cells infected with re-virus showed a 50-kDa protein that reacted with antibodies specific for beta Tub. Cells infected with the re-virus appeared to contain much higher levels of beta Tub than uninfected control cells, perhaps as much as five- to tenfold higher. Isotype-specific antibody for beta 2Tub showed little reaction in uninfected cells or cells infected with wild-type virus; strong reaction was found with cells infected with re-virus. Analysis by gel filtration of extracts of cells infected with re-virus showed that almost all beta Tub eluted in the column void volume, suggesting that it was aggregated or associated with other cell proteins. Recombinant baculoviruses producing Saccharomyces cerevisiae beta Tub were also isolated. Immunoblotting studies using antibodies specific for yeast beta Tub showed a 50-kDa protein which was absent in uninfected cells or cells infected with wt virus. Immunofluorescence studies suggest that yeast beta Tub is incorporated poorly, if at all, into the insect cell cytoskeleton. PMID- 8514192 TI - Sequence and expression of a glyceraldehyde-3-phosphate dehydrogenase-encoding gene from quail embryo fibroblasts. AB - Using differential hybridization techniques, a cDNA library derived from a line of v-myc-transformed quail embryo fibroblasts was screened for clones whose expression was elevated in transformed, as compared with normal, cells. One of the isolated clones contained the entire coding region of the quail glyceraldehyde-3-phosphate dehydrogenase-encoding gene (GAPDH). A comparison of the deduced 333-amino-acid (aa) sequence of quail GAPDH with that of the only other avian (chicken) GAPDH sequence known, and with those of mammalian counterparts indicates the strong aa sequence conservation of this glycolytic enzyme. GAPDH is expressed in all transformed and non-transformed quail and chicken embryo fibroblasts and macrophages tested, with a moderate elevation of expression in most of the transformed cell lines. In the avian genomes, GAPDH is present in a single copy, in contrast to the high number of GAPDH-related sequences in mammalian species. PMID- 8514193 TI - Cloning of the mouse hsp25 gene and an extremely conserved hsp25 pseudogene. AB - A genomic clone of the murine gene encoding the small heat-shock protein, Hsp25, was isolated. The coding region is interrupted by two introns of 128 bp and approximately 600 bp at identical positions as the human hsp27 gene. The 5' flanking regions of the mouse and human genes are very strongly conserved and contain several sequence motives for the transcription factors, HSF and Sp1. In the same screen we also isolated a hsp25 pseudogene. The sequence conservation between this pseudogene and hsp25 cDNA is very high (99%) indicating that this pseudogene emerged very recently. PMID- 8514194 TI - Structure and organisation of a murine gene encoding small heat-shock protein Hsp25. AB - The structure and sequence of a gene encoding the mouse small heat-shock protein, Hsp25, is presented and compared to the human hsp27. In contrast to the human hsp27, only two copies of hsp25 could be detected in the mouse genome. The intron exon structure of the identified hsp25 is similar to the transcribed human hsp27, and the transcription start points of the genes are located at similar sites. The promoter region contains various putative transcription factor-binding elements including two G + C-rich Sp1-binding domains, two heat-shock elements, and an estrogen-responsive element half-site in direct proximity to the TATA box. These elements could explain hsp25 basal expression as well as its induction as a result of heat-shock and estrogen treatment. PMID- 8514195 TI - Cloning of an adenosine A1 receptor-encoding gene from rabbit. AB - A partial cDNA encoding the A1 adenosine receptor (A1AR), which lacks nucleotides coding for the first 74 amino acids (aa), was isolated from a rabbit kidney cDNA library. The missing 5' end sequence was obtained from an overlapping rabbit genomic clone which was found to contain the flanking 5' untranslated region (5'UTR), the first exon and part of the first intron. Together, the cDNA and genomic clones provide the entire open reading frame (ORF) encoding rabbit A1AR. The deduced aa sequence is highly homologous to the canine, rat and bovine A1ARs. These data also indicate that the A1AR gene belongs to the family of intron containing G-protein-linked receptor genes. PMID- 8514196 TI - Bovine alpha s2-casein D is generated by exon VIII skipping. AB - Bovine alpha s2-casein D (CasD) differs from the common type A by the deletion of a stretch of 9 amino acids (aa) starting at a position not precisely known, either at aa 50, 51, or 52. The sequence of cloned PCR-amplified genomic DNA from three homozygous cows, two unrelated females carrying the CasD allele and one carrying the CasA allele, did not reveal any deletion and showed two identical nucleotide (nt) substitutions in the 1.7-kb region of both CasD alleles encompassing codons 43-75 in the cDNA encoding alpha s2-CasA. This strongly suggests that the deleted bovine alpha s2-CasD arises from skipping the 27-nt exon, now identified as exon VIII, which encodes aa 51-59 of alpha s2-CasA. The G ->T transversion (allele A-->D) affecting the last nt of exon VIII, i.e., the 5' consensus splicing site, might be responsible for the altered splicing of the primary transcript of alpha s2-CasD. PMID- 8514197 TI - Baboon lecithin cholesterol acyltransferase (LCAT): cDNA sequences of two alleles, evolution, and gene expression. AB - Lecithin cholesterol acyltransferase (LCAT) is a key enzyme of cholesterol metabolism that catalyzes esterification of cholesterol for packaging in high density lipoprotein (HDL) particles. In this study, we cloned and sequenced LCAT cDNA from baboon, a nonhuman primate model of atherosclerosis. LCAT sequences have been highly conserved over approximately 25 million years since the divergence of the baboon and human lineages. The baboon and human sequences are 97% identical at the nucleotide (nt) level and 98% identical at the amino acid (aa) level. Only 18% of the nt substitutions change the aa sequence (nonsynonymous substitutions). The substitutions between baboon and human LCAT do not alter key functional sites including the interfacial substrate active site, asparagine-linked glycosylation sites, or sites at which rare mutations cause human familial LCAT deficiencies. We also sequenced LCAT cDNA for a less common allele that is associated with higher LCAT activities and altered lipoprotein phenotypes. There were no sequence differences between the two alleles, which suggests that genotypic effects are most likely due to allelic differences in gene expression. The tissue specificity of LCAT expression was investigated using an RNase protection assay calibrated with known amounts of synthetic human LCAT RNA. In a survey of baboon tissues, the highest levels of LCAT mRNA were found in the cerebellum and liver and trace amounts in the ileum, spleen and cerebral cortex. PMID- 8514198 TI - Alternative 3' splice-site selection using HeLa cell nuclear extracts prepared with high-ionic buffers. AB - To investigate the role of cellular trans-acting factors in alternative 3' splice site selection, a series of HeLa cell nuclear extracts were generated with salt washes ranging from 0.4 to 0.8 M salt. These extracts were tested with human beta globin pre-mRNAs containing tandem 5' or 3' splice-site duplications as the substrates. High-salt (0.6 M and higher)-based buffers generated nuclear extracts that differentially processed pre-mRNAs containing competing 3' splice sites. High-salt extracts increased the usage of the distal 3' splice site, whereas no shift in 5' splice-site usage could be detected. Western analysis suggested that this shift in alternative 3' splice-site selection was not due to changes in the U2 snRNP auxiliary factor or polypyrimidine tract-binding protein levels. PMID- 8514199 TI - High-level production of biologically active human cytosolic phospholipase A2 in baculovirus-infected insect cells. AB - Infection of Spodoptera frugiperda insect cells with a recombinant baculovirus expressing human cytosolic phospholipase A2 (cPLA2) resulted in the production of biologically active protein. The level of recombinant human cPLA2 production in infected insect cells was at least 50-fold higher than that observed in human monoblast U937 cells. PMID- 8514200 TI - Role of influenza vaccination in the elderly during an epidemic of A/H1N1 virus in 1988-1989: clinical and serological data. AB - During a winter epidemic of A/H1N1 influenza virus, we evaluated the protection conferred by vaccination of 285 residents of a nursing home. Fifteen of 204 members of the nursing staff were also vaccinated. Serological determinations were performed before and after vaccination using radial hemolysis (RH) and neuraminidase inhibition (NI) tests. In the outbreak period, only one influenza case was noted in the vaccinated elderly and none among the vaccinated nursing staff. On the other hand, 38 cases (20%) occurred in the unvaccinated hospital personnel. Twenty-one percent of the elderly people exhibited seroconversion to the vaccinal strain by RH and NI while 27 and 20% of the vaccinated nursing staff seroconverted by the same tests, respectively. Thus, the clinical protection conferred by influenza vaccination was excellent and much greater than expected from serological results. PMID- 8514201 TI - Clinical parameters associated with falls in an elderly population. AB - Eighty-one elderly residents of a hostel for the aged (mean age 83.3 years) underwent clinical medical assessments to examine susceptibility to falling. The medical examination was structured and followed a clinical format with particular emphasis upon posture and gait, in addition to routine examination of the cardiovascular, respiratory, neurological, gastrointestinal, haemopoietic, genitourinary, musculoskeletal and visual systems. These subjects were then followed up for 1 year to assess whether these clinical measures were associated with falls. Seventy-six residents were available for follow-up. Thirty-four subjects (44.7%) reported having no falls in the follow-up year, 10 (13.2%) fell once only, 13 (17.1%) fell on two occasions whilst 19 (25.0%) fell three or more times. Seventy-two percent of all falls occurred in the hostel building. Certain clinical factors showed high specificity (i.e. only a few non-fallers screened positive in the tests) but low sensitivity (i.e. there were considerable numbers of residents who screened negatively, but fell in the 12-month follow-up period). Stepwise logistic regression analysis revealed impaired cognition, abnormal reaction to any push or pressure, history of palpitations and abnormal stepping as variables that independently and significantly predicted falling. The equation predicted falls with 70.7% sensitivity and 79.4% specificity, with an overall predictive accuracy of 74.7%. It appears that a modified focussed clinical examination could provide the basis of a short assessment for predicting falls and highlight possible intervention strategies for reducing fall risk. PMID- 8514202 TI - Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. AB - Clinically healthy humans as well as patients suffering from various autoimmune diseases produce natural antibodies against a variety of self-components. Such antibodies have been proposed to carry out a physiologic role in maintaining the integrity of self, as well as potentially destructive roles in the generation of autoimmune diseases. Because human autoantigens, particularly membrane proteins, are usually present in extremely small amounts, it is generally impossible to obtain enough to carry out a detailed characterization of the antibodies or the antigenic determinants recognized. To circumvent this difficulty, we developed synthetic autoantigens predicted from the gene sequence of two functionally critical membrane proteins; the band 3 anion transport protein which is found on all cells, and the T-cell receptor (beta chain) which is the antigen-specific receptor on thymus-derived lymphocytes. We have investigated the natural human IgM and IgG antibody responses to peptides selected on the basis of predicted molecular surface exposure and previously known antigenicity, and correlate levels of binding with changes in age and by comparison with autoimmune diseases. We report that the IgM response to synthetic autoantigens tends to be higher than that of IgG molecules, but significant IgG binding occurs to some peptides. This situation is particularly noticeable in comparison of rheumatoid arthritis patients with normal individuals. Distinct peptide portions of individual molecules are recognized differently by the autochthonous immune system as manifested by age dependence of the response and differential levels of IgM and IgG activity. The synthetic autoantigens that tend to generate the highest amounts of natural antibody are those that are either exposed on the surface of the cell (band 3 peptides) or are exposed in the predicted 3-dimensional folding of the molecule (T-cell receptor beta peptides). Rheumatoid arthritis patients tend to give higher IgM reactivities to both band 3 and Tcr beta peptides than do normals, with this effect being less pronounced in the distinct autoimmune disease systemic lupus erythematosus. Studies of normal humans ranging in age from 20 to 90 years suggest two major patterns for the IgM natural antibody response to synthetic peptides giving high response. The first is that the level of IgM reactivity is high early in life and remains high throughout. The second pattern is one in which the reaction is high in younger individuals, but diminishes substantially in the latter decades of life.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8514203 TI - Morphometric analysis of the muscle fibres of the soleus muscle of the ageing rat: long-term effect of hypophysectomy and food restriction. AB - This communication reports on the effects of ageing, hypophysectomy and food restriction on the fibre sizes of the soleus muscle which is primarily concerned with posture. The results reported here are compared with those previously shown for the gastrocnemius muscle which is involved mainly with locomotion. Muscle fibre size (measured as equivalent circle diameter) in the soleus muscle of the male Wistar rat increased from youth at 130 days (type 1 fibres, 61.2 microns; type 2, 58.3 microns) to middle age at 600 days (type 1 fibres, 70.4 microns; type 2, 68.0 microns) and then underwent atrophy in old age to 1,000 days (type 1 fibres, 54.5 microns; type 2, 38.0 microns). There was no growth or atrophy of these fibres in either hypophysectomized or food-restricted rats. There was an increased range of fibre sizes in control rats between youth and old age being 5 fold for type 1 fibres and 3-fold for type 2 fibres, but there was a loss of type 2 fibres in hypophysectomized rats. This ageing process in the range of fibre size was retarded by hypophysectomy (2-fold increase for type 1 fibres) and to a lesser extent by food restriction (3-fold increase for type 1 fibres). Muscle fibre atrophy and compensatory hypertrophy were not as prominent in the hypophysectomized and food-restricted groups as in the old control groups. In general these effects were similar to those previously shown for the gastrocnemius muscle. However, atrophy of both type 1 and type 2 fibres in old age was more pronounced in the soleus muscle. The retarded ageing of the soleus muscle in hypophysectomized and food-restricted rats was probably due to the absence or reduced circulating levels of hormones known to target muscle cells, such as growth hormone and thyroxine. PMID- 8514204 TI - Accessory function and properties of monocytes from healthy elderly humans for T lymphocyte responses to mitogen and antigen. AB - The waning of cell-mediated immunity during aging has been attributed primarily to defects in T lymphocyte properties and functions. We assessed the potential contribution of accessory dysfunction of monocytes from the elderly on responses of T cells to phytohemagglutinin (PHA) and to tetanus toxoid after in vivo boosting. Accessory function of monocytes from the elderly subjects for T lymphocyte responses to tetanus toxoid was comparable to the young. Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar. T lymphocytes from the elderly responded poorly to PHA. Monocytes from the elderly had a decreased accessory function for PHA-stimulated T cells from young, third donors. Thus, although many accessory properties of monocytes from the elderly are normal, the monocyte and T lymphocyte defects in the elderly for mitogen may represent interactive factors in cell-mediated immunity during aging. PMID- 8514205 TI - [Screening method for nootropics--method for evaluation of latent learning]. PMID- 8514206 TI - [Biological regulation by the kallikrein-kinin system: a study with a kininogen deficient rat strain]. AB - It is well known that the kallikrein-kinin system expresses potent biological activities through its final product, bradykinin. However, bradykinin has an extremely short half life in biological fluids, so that it is difficult to quantitate the amount of bradykinin released in relevant pathological samples. Therefore investigators have attempted to prove its involvement or importance by measuring the precursor proteins, such as prekallikrein, kininogens, and glandular kallikreins. In this review, I would like to focus the discussion on a study of the kallikrein-kinin system in B/N Katholiek rats, a strain that has a congenital deficiency in plasma high molecular weight and low molecular weight kininogens. When experimental inflammation induced in the mutant deficient rats are compared to that induced in the normal rats (B/N-Kitasato), there was a significant difference; i.e., the deficient rats showed less swelling in the carrageenin-induced paw edema and less exudate accumulation in carrageenin induced rat pleurisy. These results indicate that bradykinin may be released from kininogens and it may cause exudate formation in above inflammation. Furthermore, when experimental hypertension was induced by DOCA-salt loading, the blood pressure of the deficient rats rose faster than that of the normal rats. From the above findings, it is concluded that the plasma kallikrein-kinin system could be an important regulatory system in body defense mechanisms such as inflammation and blood pressure control. PMID- 8514207 TI - [Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs]. AB - Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF. PMID- 8514208 TI - [General pharmacological studies on human natural tumor necrosis factor (MHR 24)]. AB - The general pharmacological properties of MHR-24 were studied in various experimental animals. Intravenously (i.v.)-administered MHR-24 at 8.6 x 10(2) JRU/kg or more produced fever in rabbits. MHR-24 at 3 x 10(4) JRU/kg or more caused tachycardia; and at 1 x 10(5) JRU/kg or more, it lowered arterial blood pressure in anesthetized monkeys. In rats, MHR-24 at 2.9 x 10(4) JRU/kg or more showed a diuretic action and inhibitory effects on gastric juice secretion and carrageenin-induced paw edema. Furthermore, MHR-24 at a large dose (8.6 x 10(4) or 2.9 x 10(5) JRU/kg, i.v.) decreased spontaneous locomotor activity, had an inhibitory effect on acetic acid-induced writhing and potentiated intestinal propulsion in mice; and it caused the appearance of rest wave on acute spontaneous electroencephalograms in rabbits. Pretreatment of the animals with the cyclooxygenase inhibitor indomethacin abolished the fever and potentiation of intestinal propulsion caused by MHR-24. Therefore, these data seem to indicate that some of the effects of MHR-24 are mediated via cyclooxygenase pathways. The results suggested that, except for the above results, MHR-24 has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and others in general pharmacological studies. PMID- 8514209 TI - [Central effects of iohexol and iopamidol, non-ionic contrast media]. AB - Central effects of intravenously (i.v.)-administered iohexol were compared with those of iopamidol in a series of tests. Mannitol was used as a reference. As assayed by the primary screening test based on Irwin's method, i.v. administration of mannitol resulted in a score of 0 in ddY mice and a score of 0.6 in ICR mice in the startle response. These results were not different from the data of both iohexol and iopamidol. Iopamidol at a dose of 1750 mgI/kg produced an inhibitory effect on the spontaneous locomotor activity. Iohexol at a dose of 7000 mgI/kg potentiated the duration of thiopental-induced narcosis. Hypothermia was caused by high doses of both iohexol and iopamidol. Electric stimulus increased the mortality of mice pretreated with high doses of iohexol and iopamidol. Both drugs had no notable activities in the anticonvulsant, electroencephalic, muscle relaxant and antinociceptive tests. These results indicate that both iohexol and iopamidol do not necessarily possess a similar pharmacological action. Judging from the LD50 of approximately 15000 mgI/kg for both drugs, they seem unlikely to have a specific pharmacological action on the central nervous system. PMID- 8514210 TI - [Inhibitory effects of palonidipine hydrochloride (TC-81) on contractions induced by various vasoconstrictors in rat aorta]. AB - Inhibitions by palonidipine hydrochloride (TC-81), a new Ca entry blocker, of the contractile responses to norepinephrine (NE), serotonin (5-HT), prostaglandin F2 alpha (PGF2 alpha) and U-46619, a thromboxane A2 analog, were investigated in isolated rat aorta strips and compared with the inhibition of the high K+ response. TC-81 and nicardipine inhibited the contractile responses to NE, 5-HT, PGF2 alpha, and U-46619 in a concentration-dependent manner, but their relative inhibitions were less than 50% at 10(-8) M. In a Ca(2+)-free medium, 2-hr pretreatment with TC-81 or nicardipine did not inhibit the contractile responses to various vasoconstrictors, but it inhibited the responses to the addition of Ca. Their inhibitory potencies were less than the inhibition with high K+. Also, the treatment with TC-81 or nicardipine at 10(-7) M did not affect the tissue level of cyclic AMP. These results suggest that in isolated rat aorta, the inhibition by TC-81 of the contractile responses to NE, 5-HT, PGF2 alpha and U 46619 is not due to inhibition of intracellular Ca2+ release or an increase in cyclic AMP; rather, it is due to inhibition of the Ca2+ influx. This inhibitory effect was less than that seen on the high K+ response. PMID- 8514211 TI - Cell-cycle and ploidy analysis in bone marrow and liver cells of rats after long term consumption of irradiated wheat. AB - Rats were fed for 4 or 90 days either with 70% freshly irradiated wheat (0.25, 0.75 or 2.25 kGy) and 30% complementary feed or with a control diet. None of the parameters examined (food consumption, body weight, haematological analysis, histopathological inspection of thymus, lung, liver, spleen and kidney, DNA analysis of bone marrow cells and nuclei from liver cells by flow cytometry) showed any statistically significant association with the feeding regimen. Minor changes in ploidy of liver cells and cell cycling of bone marrow cells were detectable (wheat-irradiation dose-dependent increase in G2/M-phase bone marrow cells up to 0.6%, decrease of 8C nuclei up to 1.1% in liver cells). From the pattern of alterations observed in our study, radiolytic by-products of wheat irradiation with a spindle poison-like activity can be excluded. Polyploid cells do not accumulate within the 90-day feeding period. The minor effects on cell cycle and ploidy observed are qualitatively comparable with the effects seen after food restriction in animal studies. It is suggested that an altered composition of fatty acids (the components of wheat most sensitive to irradiation) is responsible for these marginal effects. Our findings may explain the earlier findings of Bhaskaram and Sadasivan (American Journal of Clinical Nutrition 1975, 28, 130-135) who reported an increase in the number of polyploid cells in the lymphocytes of malnourished children fed irradiated wheat. The most likely mechanisms for such an effect are adaptive, constitutively regulated processes, similar to those which respond to food restriction. It is concluded that the consumption of irradiated wheat does not, therefore, pose any health risk to humans. PMID- 8514212 TI - Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays. AB - A short-term rat liver cancer initiation/promotion model was used to monitor the cancer-initiating activity of the mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2) and fumonisin B3 (FB3) as well as the N-acetyl derivatives of FB1 and FB2, and their respective hydrolysis products the aminopolyols. The induction of resistant hepatocytes, which develop into hepatocyte nodules on selection by the 2-acetylaminofluorene-partial hepatectomy promoting treatment, was taken as the endpoint for cancer initiation. When fed at a level of 1000 mg/kg diet for 21 days, only the fumonisins B were found to initiate cancer. In addition, these mycotoxins caused a marked reduction in the rat body weight during the initiating treatment. Comparative cytotoxicity studies in primary rat hepatocytes indicated that FB2 exhibited the highest cytotoxic effect followed by FB3 and FB1. In general, the fumonisin B mycotoxins exhibited a low cytotoxic effect in hepatocyte cultures, and the concentrations of FB1 and FB2 that caused a 50% (CD50) release of the total lactate dehydrogenase (LDH) were in the order of 2000 and 1000 microM, respectively. The N-acetyl derivatives also exhibited a cytotoxic effect, but were not as cytotoxic as the parent molecules at high concentrations. The respective aminopolyols exhibited a higher cytotoxicity than did the parent compounds, while tricarballylic acid (TCA) exhibited no dose response effect despite the fact that it had a higher background cytotoxicity compared with the control. The apparent inability of the aminopolyols to act as cancer initiators could be related to a lack in absorption from the gut.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514213 TI - Effect of 3-methylcholanthrene induction on the distribution and DNA adduction of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in F344 rats. AB - 3-Methylcholanthrene (3MC) is a potent inducer of the cytochrome P450IA family of enzymes that catalyses the metabolic activation of the food mutagen/carcinogen 2 amino-3-methylimidazo[4,5-f]quinoline (IQ). We have examined the effect of pretreatment with 3MC on the distribution and DNA adduct formation of IQ in male Fischer F344 rats. 3 hr after a single dose of [14C]IQ (10 mg/kg body weight, by gavage), the level of radioactivity in extrahepatic tissues was 30-70% less in 3MC-pretreated rats than in vehicle control rats. Although the level of radioactivity in the liver did not change after 3MC pretreatment, IQ-DNA adduct levels, measured by the 32P-postlabelling method, were 60% lower in the livers of 3MC-pretreated rats than those of control rats, and 83-97% lower in extrahepatic tissues such as the kidneys, colon, small intestine, bladder, heart and lung. IQ DNA adducts in the testes and brain were found in control rats but were not detected in 3MC-pretreated rats. The rate of removal of IQ-DNA adducts from the livers of control and 3MC-pretreated animals was the same from 3 to 48 hr. At 48 hr, the adduct level in 3MC-pretreated rats remained lower than that seen in the control rats. The data suggest that 3MC induction of the P450IA family of cytochromes in vivo results in an increased rate of IQ detoxification. PMID- 8514214 TI - Plasma lipids and liver histochemistry of rats fed sea-lion or corn oil with or without cholesterol supplementation. AB - Sea-lion oil (SO) is used as a dietary supplement in the treatment of cardiovascular disease. The effects of SO on plasma lipid concentration and liver lipid histochemistry were compared with those of corn oil (CO). Male Sprague Dawley rats were fed diets containing 15% (w/w) SO or CO with or without 1% cholesterol for 25 days. Compared with rats fed CO, SO-fed rats showed lower plasma cholesterol levels (P < 0.001), high-density lipoproteins (HDL) (P < 0.05), very-low-density lipoproteins (P < 0.05), triglycerides (P < 0.05) and total lipids (P < 0.05). Rats fed SO and cholesterol had lower plasma concentrations of cholesterol (P < 0.001) and HDL (P < 0.05) than those of animals fed CO. Alterations in liver cytology were observed in rats fed SO, including a differential accumulation of lipids in the canalicular regions of hepatocytes and a high density of lipid vesicles in hepatic lobule triads. The results indicated that, compared with CO, SO reduces plasma lipid levels and causes histochemical changes associated with an increased excretion of lipids from the liver. PMID- 8514215 TI - Effect of ascorbic acid in the detoxification of the insecticide dimethoate in the bone marrow erythrocytes of mice. AB - The antimutagenic potential of ascorbic acid in the detoxification of the organophosphorus insecticide dimethoate was evaluated in female Swiss albino mice using the in vivo bone marrow micronucleus test. Groups of three mice were treated with distilled water (control), 1% dimethyl sulphoxide (solvent control), or 86, 129.5 or 259 mg ascorbic acid/kg body weight, with or without the concurrent administration of 150 mg dimethoate/kg. There was a statistically significant increase in the frequency of micronuclei in dimethoate-treated mice. However, in mice that were given dimethoate and ascorbic acid simultaneously, the numbers of micronuclei did not differ significantly from control values, thus indicating the protective role of ascorbic acid. PMID- 8514216 TI - Dose-dependent genotoxic effect of pan masala and areca nut in the Salmonella typhimurium assay. AB - Aqueous extracts of different brands of pan masala and scented supari were tested for mutagenicity by the Salmonella typhimurium assay using tester strains TA98 and TA100. These extracts were found to be mutagenic to both tester strains. The mutagenic effects of pan masala and scented supari extracts were similar to that produced by areca nut extract. The addition of 500 ppm saccharin to the supari extracts did not alter the mutagenic response. PMID- 8514217 TI - Gastro-intestinal availability of aluminium from tea. AB - The in vitro speciation of aluminium (Al) in black tea infusion (pH 4.8) was assessed using 3000, 10,000 and 30,000 Da cut-off ultrafilters, and the effect of adding human gastric juice (pH 2.3) and then raising the pH to 6.5 were also studied. 78% Al in the tea infusion passed through the 3000-Da ultrafilter; this percentage increased to more than 90% with the addition of gastric juice at pH 2.3, but then reduced to approximately 5% when the incubate was adjusted to pH 6.5. The breakdown of tea-derived polyphenols to low molecular weight phenols in vivo was measured using high-resolution 1H nuclear magnetic resonance spectroscopic analysis of ileostomy effluent, but there was no evidence of low molecular weight breakdown products from the polyphenols of ingested tea in this effluent. These results suggest that only a small proportion of Al in tea is potentially available for absorption throughout the small bowel. It may be misleading to estimate systemic Al absorption from tea drinking simply from total urinary aluminium excretion as has been done previously. PMID- 8514218 TI - The toxicological hazards of patulin. PMID- 8514220 TI - Infant diets. PMID- 8514219 TI - Nutrition in elderly people. PMID- 8514221 TI - [Therapy of acute myocardial infarct with thrombolytic drugs. Can use of thrombolytic therapy be further improved?]. PMID- 8514222 TI - [Psychological processing of environmental anxiety. Dilemma of physicians- insecurity of patients]. PMID- 8514223 TI - [Cardiovascular risk factors in former and new Germany. City comparison of Leipzig/Nurnberg on the incidence of increased cholesterol values and other cardiovascular risk factors]. AB - FUNDAMENTALS: Cardiovascular risk factors depend decisively on living conditions and nutrition. The aim of the present study was to establish whether the different living conditions in the eastern and western parts of Germany were associated with differences in the frequency and severity of these risk factors. METHOD: In Leipzig, 15,291 people (9,600 women and 5,691 men), in Nuremberg 8,387 (4,559 women and 3,828 men) were examined either after responding to a public appeal, or in the factory, etc. RESULTS: Clearly elevated cholesterol levels (> 250 mg/dl) were found in 33.8% of the men, and 35.9% of the women in Leipzig, and in 39.1% of the men and 50.7% of the women in Nuremberg. This larger incidence of treatment-requiring hypercholesterolemia in Nuremberg was distributed throughout all age groups up to the age of 60. Hypertension was significantly more common among the 30 to 80-year-old women, and the 20 to 40-year-old and 50 to 80-year old men in Leipzig. the frequency of cigarette smoking, diabetes mellitus and overweight did not differ significantly between the two cities. In cases with known dyslipoproteinemia, drug treatment was rarely applied, and the therapeutic aim of a cholesterol level < 200 mg/dl, was achieved in only 2-6% of those treated. The most significant difference with respect to cardiovascular risk factors was serum cholesterol. It is possible that a higher ingestion of monounsaturated fatty acids and more physical activity may be responsible for the lower cholesterol levels in Leipzig. PMID- 8514224 TI - [Toxic megacolon in pseudomembranous colitis. Complicated course of antibiotic induced Clostridium difficile colitis]. AB - We report on a patient with antibiotic-induced pseudomembranous colitis aggravated by toxic megacolon. Colonoscopy not only rapidly permits the diagnosis to be established, but the relief of pressure achieved simultaneously also has a therapeutic effect. If treatment comprising parenteral fluid and electrolyte replacement in combination with oral vancomycin fails to effect an improvement, surgery becomes necessary. Current recommendations for treatment are discussed on the basis of a review of the literature. However, a major preventive measure remains the rational use of antibiotics. PMID- 8514225 TI - [Peptic ulcer hemorrhage--diagnostic-therapeutic procedure]. PMID- 8514226 TI - [Treatment of hypertension with consideration of metabolism. A challenge for current therapy of essential hypertension]. AB - In the modern therapeutic approach to hypertension, the aspect of "metabolic side effects" is receiving ever more attention. This is the result of the recognition that high blood pressure forms part of a metabolic syndrome known as syndrome X, the components of which are variously influenced by different antihypertensive agents. Of particular importance seems to be the response of an underlying insulin resistance, since resulting hyperinsulinemia has been shown to be a separate risk factor. Negative metabolic influences on this syndrome may be a reason for inadequate prevention of coronary heart disease, as has been observed under conventional treatment despite effective lowering of blood pressure over many years. The spectrum of relevant antihypertensive drugs contains only few "metabolically neutral" or "metabolically positive" classes of substances, so that particular importance must be attached to ACE-inhibitors for use in patients with a "metabolic risk"; the most thoroughly studied of such inhibitors is captopril. In order to increase the responder rate to about 90%, a combination with low-dose hydrochlorothiazide can be recommended; the negative effect of the thiazide on insulin sensitivity is balanced by the positive effects of captopril. The great practicability of the single dose form of administration, the synergism of the individual substances, and "metabolic neutrality", together with the high level of tolerability underscore the advantage of this combination treatment. PMID- 8514227 TI - [HIV infected patients usually treated as outpatients. H. Jager, Munich, on the management of AIDS patients in general practice]. PMID- 8514228 TI - [Tamed chaos]. PMID- 8514229 TI - [The antidepressive effect of REM sleep deprivation. Etiology of depression: an imbalance of aminergic and cholinergic activity]. PMID- 8514230 TI - My experience as a courier. PMID- 8514231 TI - My experience as a courier. PMID- 8514232 TI - [Methyl alcohol poisoning]. PMID- 8514233 TI - [Comparison of onchocerciasis between Central and South Americas: a tragic tropical rain forest]. PMID- 8514234 TI - [Generation of a monoclonal antibody specific to human T cell receptor V beta 22, and analysis of peripheral blood T cell repertoire utilizing this monoclonal antibody]. AB - A murine monoclonal antibody, R1-21, against a HLA-DR4 restricted CD4+ T cell line specific to streptococcal cell wall (SCW) Ag was generated. R1-21 reacted with about 50% of the HLA-DR4 restricted CD4+ T cell line. R1-21 distinguished a diversity of TCR because it reacted with a small population of peripheral T lymphocytes, induced proliferative response in peripheral blood lymphocytes, immunoprecipitated a cell surface molecule of 80 kDa in non-reduced condition and 45 and 40 kDa in reduced condition, and the immunoprecipitates with R1-21 was precleared with a known anti-TCR mAb. Sequence analysis of cDNA clones corresponding to TCR alpha and beta genes derived from R1-21 positive and negative T cell lines revealed that R1-21 recognized a V beta 22 gene product. By utilizing R1-21, it was found that V beta 22 positive cells existed 3.80 +/- 0.94% and 3.56 +/- 0.59% in healthy adult and neonatal cord blood T lymphocytes, respectively, and a V beta 22 gene product was skewed expressed on CD4+ T cells. (CD 4/CD 8 ratio: 1.69 +/- 0.57). PMID- 8514235 TI - [Immunogenetic analysis of rheumatoid arthritis in the Japanese population]. AB - To reveal immunogenetic factors involved in the pathogenesis of rheumatoid arthritis(RA), two hundreds and four unrelated Japanese patients with RA were typed for HLA by both serologic typing and DNA typing using polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Serologic HLA typing data showed that frequencies of HLA-A11, DR4, DR53, and DQ4 were increased and those of DR8, DR52, and DQ1 were decreased in the patient group. The HLA-DNA typing has defined more precisely the disease-associated HLA-class II alleles and revealed that DRB1*0405, DQA1*03, and DQB1*0401 were strongly associated with the disease susceptibility whereas DRB1*0803, DQA1*0103, and DQB1*0601 showed negative association with RA. Comparison of amino acid sequences of DRB1*0405 with other DRB1 alleles suggested that the risk for RA was closely associated with particular amino acid residues of DR beta chain, i. e. glycine residue at the 86th position in addition to the residues between 70th and 74th position. The significant decreased frequency of DRB1*0803 in the DRB1*0405 positive patient group suggests that DRB1*0803 may control resistance to RA as a dominant genetic trait. In addition, the observation that the frequency of DPB1*0201 was increased in the DRB1*0405 negative patient group may indicate that the disease susceptibility to RA is controlled by the HLA-DP region in the minority of the patients. The polymorphism of TAP2 gene and TCR genes showed no significant association with RA, suggesting that the contribution of these genes to the susceptibility is relatively small, if any. PMID- 8514236 TI - [Effectively treated hypertension with minocycline hydrochloride infusion into the cyst in a patient with a multi-septated massive hepatic cyst]. AB - We present a successfully treated case of a multi-septated massive hepatic cyst with repeated injection of minocycline hydrochloride (MINO). A 57-year-old Japanese female complaining of right back pain, hypochondralgia and hypertension had a multi-septated massive hepatic cyst, 25 cm in diameter. Multiple cysts of various sizes were also seen in liver and kidneys. In order to reduce the size of the massive hepatic cyst to relieve the complaints, we performed the reduction therapy of the cyst. After a pig tail catheter was inserted into the cyst, the cystic fluid was aspirated and then a total of 3900 mg of MINO was injected. Red brownish, serous cystic fluids were obtained. Cytology and bacterial culture were negative, but the LDH (3, 336 IU/l) and CA19-9 (751,500 U/l) concentrations were very high. After the 9 series of the therapy, the cyst was minified on CT and the patient's symptoms were relieved. Furthermore high blood pressure was improved. Thus, the therapy of size-reduction for a massive hepatic cyst is revealed to be very safe and useful. PMID- 8514237 TI - Contemporary insights into the control of the corpus luteum function. AB - Increasing evidence has been accumulated to confirm the critical dependency of the corpus luteum function from regular pituitary luteinizing hormone (LH) inputs. In fact, close temporal and functional links have been demonstrated between intermittent LH stimulations and episodic sex steroid release emanating from the mature corpus luteum. Moreover, an intrinsically pulsatile progesterone (P4) release independent of, but facilitated by gonadotropin inputs has been observed from the corpus luteum in vitro. This may suggest some functional autonomy in this organ, at least within close temporal limits. The pulsatile P4 secretion may be optimally maintained by gonadotropin stimulations effected at frequencies and amplitudes similar to those observed during the luteal phase in vivo. Since autonomous P4 secretion is modulated, amongst other determinants, by prostaglandins, oxytocin and P4 itself, ultra-short feedback loops are assumed to exist for an optimal tuning of the luteal function. This episodic sex steroid release from the corpus luteum may be required to set the endocrine signal for the blastocyst to implant. PMID- 8514238 TI - Streptozotocin-induced diabetes mellitus in pigs. AB - We induced, as a precondition for a pancreas transplant, insulin-dependent diabetes mellitus in 67 Yorkshire Landrace pigs by administering streptozotocin. A dosage of 150 mg/kg body weight gave rise to a long-lasting diabetes mellitus that persisted with time (follow-up period: 26 weeks). Consecutive measurements of serum glucose and plasma insulin, before and up to 30 hours after administering streptozotocin, revealed triphasic behavior: initial hyperglycemia (1st to 3rd hour), pronounced hypoglycemia (12th to 18th hour), then hyperglycemia (22nd hour on). IVGTTs done 1 to 7 days after administering streptozotocin revealed a reduction of the K-value (glucose disappearance rate) from 0.3 (day 2) to 0.07 (day 4). Immunohistochemical studies revealed a complete loss of all beta-cells, concomitantly with a relative increase in glucagon- and somatostatin-positive cells. We also observed a complete loss of pp (pancreatic polypeptide)-positive cells. Diabetes induced by streptozotocin at 150 mg/kg body weight is complete and permanent; our mortality rate was 0%. Given the high morbidity rate after pancreatectomy, streptozotocin should be the method of choice for inducing diabetes mellitus in pigs. PMID- 8514239 TI - Long-term function of porcine islets and single cells embedded in barium-alginate matrix. AB - The influence of alginate-embedding on the maintenance of functioning and morphological integrity in long-term culture of isolated porcine islets and islet cells was studied. Free-floating islets and islet cells served for control. Function was tested after the 1st, 2nd and 4th week. Basal and glucose-stimulated insulin secretion of embedded islets decreased slightly, but significantly after the first week (from 4.39 +/- 0.64 to 2.87 +/- 0.47 at normal and from 11.96 +/- 1.44 to 4.76 +/- 0.78 microU pro 24 h pro islet at elevated glucose concentration, p < 0.05 and < 0.01, resp.) and remained unchanged thereafter. Glucose-stimulation resulted in significant increases in insulin secretion at all three testings (p < 0.001, < 0.01 and < 0.01). Single cells in alginate matrix had even more stable insulin secretion throughout the whole cultivation with significant increases to glucose challenge (p < 0.01, < 0.01 and < 0.05). In contrast, insulin secretion of free-floating islet cells decreased from 5.70 +/- 1.19 to 2.04 +/- 0.64 and to 1.05 +/- 0.33 at basal conditions (p < 0.01 and < 0.05) and from 11.39 +/- 1.87 to 2.76 +/- 0.76 and to 2.15 +/- 0.71 microU pro 24 h pro islet under stimulation (p < 0.01 and not sign). In addition, the secretory response to glucose challenge was significant only at the first testing (p < 0.05). Non-embedded islets could be tested only at the first week since after this time they dissociated to single cells. Embedded islets and single cells showed intact morphology after four weeks with trypan blue (TPB) positivity of less than 5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514240 TI - Glucose transport during cell cycle in IM9 lymphocytes. AB - Hexose uptake of the transformed lymphocyte cell line IM9 was analysed with respect to kinetics, responsiveness to insulin and insulin-like growth factor I and to cell cycle dependency. We found a Km of 0.76 mM and a Vmax of 14.9 nMol/min/mg protein for 2-deoxy-D-[3H]glucose uptake. This Km is in accordance with the values described for the erythrocyte type and the brain type glucose transporter. Hexose uptake of IM9 lymphocytes was not altered by physiological concentrations of insulin or IGF I. We investigated the 2-deoxy-D-[3H]glucose transport in cells, enriched in the different cell cycle phases by counterflow elutriation. The results were calculated for hypothetical pure fractions. Hexose uptake per cell is more than doubled during the S-phase and returns in G2-cells to the basal value of G1-phase. PMID- 8514241 TI - Endocrine control of sheep adipose tissue fatty acid synthesis: depot specific differences in response to lactation. AB - The effects of lactation and insulin, growth hormone and dexamethasone (a glucocorticoid analogue) have been assessed on the rate of fatty acid synthesis in adipose tissue from omental (abdominal), subcutaneous and popliteal (intermuscular) depots of sheep. Adipocyte mean cell volume was greatest in omental tissue but the rate of fatty acid synthesis was similar in omental and subcutaneous adipose tissue in non-lactating ewes. Insulin increased the rate of fatty acid synthesis in tissue from all three depots and this was antagonised by growth hormone. The effects of growth hormone were less in omental adipose tissue from non-lactating sheep than in the other two depots. Lactation decreased the rate of fatty acid synthesis in all three depots, but to a lesser extent in omental than the other depots. Insulin resistance was apparent in subcutaneous and popliteal tissues from lactating ewes but not in omental tissue. Omental adipose tissue, thus differs in several aspects from the two carcass depots. Differences in response to hormones in omental adipose tissue were apparent in young sheep before the onset of fattening when omental adipocytes are similar in size to subcutaneous adipocytes. PMID- 8514242 TI - The effect of chronic nicotine administration on bone mineral content in mice. AB - Tobacco use has been identified as being a risk factor for the development of osteoporosis. To elucidate the effect of nicotine on bone metabolism we examined 8 intact and 8 castrated mice treated for 56 days with nicotine in drinking water and compared with the same number of mice acting as controls. The mineral bone mass in the femora of the animals was measured quantitatively. A significant reduction of bone density and bone mineral content was found in the nicotine treated animals compared to animals without nicotine. Nicotine itself does not exert any antiandrogenic effect, and it does not produce changes in the weight of seminal vesicles. PMID- 8514243 TI - Chronic effects of interleukin-1 beta on fever, oxygen consumption and food intake in the rat. AB - Chronic subcutaneous infusion (from osmotic minipumps) of IL-1 beta (1 microgram/d) in male rats over seven days caused transient (1-3 d) increases in body temperature and reductions in body weight gain and food intake. By day 3, when colonic temperature was similar for vehicle and IL-1 infused groups, the acute responses (increases in temperature and VO2) to a maximal dose (1 microgram, sc) of IL-1 beta was almost identical in all animals. In a separate study intraperitoneal infusion of the same dose of IL-1 beta (1 microgram/d) increased the duration of changes in body temperature, weight and food intake, compared to subcutaneous infusion. In further groups of rats, pyrogenic responses to daily injections of IL-1 beta (1 microgram ip) were sustained for the entire 7 d period, but this treatment did not affect body weight. These data demonstrate that tolerance to infusion of IL-1 is not accompanied by reduced maximal responses to acute administration of IL-1, and indicate that more sustained effects of IL-1 are achieved by intraperitoneal rather than subcutaneous infusions, or by repetitive daily injections of the cytokine. These observations indicate that low levels of IL-1 release, maintained over periods of several days could be responsible for changes in body temperature and energy balance during chronic infections or inflammation. PMID- 8514245 TI - Human uterine protein in relation to infertility. AB - The concentration of electrophoretic protein in the uterine fluid of infertile women is significantly higher at all the phases of the menstrual cycle, except at phase I where it is significantly (p < 0.01) lower than parous women. At phase III (ovulatory phase) the concentration of electrophoretic protein (2812.00 micrograms/ml) is maximum in infertiles, and shows a highly significant (p < 0.001) increase over that of parous women (954.85 micrograms/ml). The highest level of electrophoretic protein at phase III in infertile women is due to maximum increase in anodic (electronegative) protein at this stage. This suggests that significant (p < 0.001) increase in concentration of anodic protein in the uterine fluid of infertile women at the ovulatory phase adds negative charge on sperm membrane that may possibly affect the capacitation of spermatozoa, thus causing infertility in women. PMID- 8514244 TI - Distribution of free amino acids in human preovulatory follicles. AB - The purpose of the present study was to investigate the possible role of intrafollicular amino acids in the human ovarian follicle. Follicular fluid (FF) and oocytes were obtained from 12 women for in vitro fertilization. Follicular development was induced with clomiphene citrate and human menopausal gonadotropin. Thirty-six FF samples, free of visible blood contamination and containing mature oocytes were used to measure free amino acids, steroids and gonadotropins. The FF were divided into three groups: (1) follicles yielding oocytes that were unfertilized (n = 12); (B) follicles containing oocytes that were fertilized and cleaved to less than four cells (n = 12); (C) follicles yielding oocytes that were fertilized and cleaved to four or more cells (n = 12). The concentrations of histidine, phenylalanine and asparagine in FF were significantly greater than those in plasma at the time of follicle aspiration. However, amino acid concentrations in FF did not differ significantly between the three groups studied. No significant relationships were found between intrafollicular levels of amino acids and those of LH, FSH, estradiol, progesterone and testosterone. These results suggest that intrafollicular amino acids are not involved in the regulation of human preovulatory follicle. PMID- 8514246 TI - Insulin regulates plasminogen activator production in two porcine thyroid cell lines. PMID- 8514247 TI - Mitotane (o,p'-DDD) administration raises the serum level of high density lipoprotein (HDL) in normotriglyceridemia. PMID- 8514248 TI - Influence of human leukocyte antigen matching on liver allograft survival and rejection: "the dualistic effect". AB - To date only one published large series of human leukocyte antigen matching and liver allograft survival exists, and considerable confusion has arisen about the advantage or disadvantage of human leukocyte antigen matching. In the present study we have reinvestigated the relationship between human leukocyte antigen mismatch and graft survival in 466 first liver allografts, seeking to clarify the relationship between human leukocyte antigen and both acute rejection and the vanishing bile duct syndrome. In view of current criticism regarding the accuracy of serological tissue typing for human leukocyte antigen-DR, we have used both classic serology and restriction fragment length polymorphism analysis to ensure the accurate assignment of recipient DR types. In addition, we have used polymerase chain reaction amplification and allele-specific and sequence-specific oligonucleotide probes to retest the hypothesis that human leukocyte antigen class II matching may increase susceptibility to the vanishing bile duct syndrome. One-year graft survival was significantly lower in patients with zero or two human leukocyte antigen-A mismatches (52% and 63%, respectively) than in those with one human leukocyte antigen--A mismatch (69%) (p = 0.016 and p = 0.018). A similar effect of B mismatching was observed, with a 1-yr graft survival of 73% for those with one compared with 60% for those with two human leukocyte antigen-B mismatches. In contrast no correlation was found between DR mismatch and graft survival. Human leukocyte antigen class I matching appears to influence graft survival largely through the occurrence of acute rejection and the development of the vanishing bile duct syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514249 TI - Distribution of body water in patients with cirrhosis: the effect of liver transplantation. AB - We compared total body water and intracellular-extracellular distribution of body water between male patients with mild liver disease without ascites (n = 9), male patients with severe liver disease and gross ascites (n = 6) and a group of age-, sex-, height- and weight- matched controls (n = 6). In addition, we documented the effects of liver transplantation on intracellular, extracellular and total body water in 12 patients (6 men and 6 women) by means of deuterium oxide dilution and whole-body potassium counting. We saw no significant difference in total body water between the healthy controls, patients without ascites and patients with ascites (46.5 +/- 9.2 kg, 45.4 +/- 6.6 kg and 50.4 +/- 5.1 kg, respectively), although, as expected, extracellular water was increased in patients with ascites compared with healthy controls and cirrhotic patients without ascites (36.9 +/- 6.5 kg vs. 25.4 +/- 4.4 kg, p = 0.005; and 36.9 +/- 6.5 kg vs. 27.0 +/- 5.3 kg, p = 0.002, respectively). We found no difference between non-ascitic patients and healthy controls (25.4 +/- 4.4 kg vs. 27.0 +/- 5.3 kg). However, intracellular water was significantly reduced in patients with severe liver disease compared with that in controls (13.6 +/- 3.3 kg vs. 21.5 +/- 4.2 kg, p = 0.005) or patients without ascites (13.6 +/- 3.3 kg vs. 18.3 +/- 2.9 kg, p = 0.01). The reduction of intracellular water appears to be due to loss of body cell mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514250 TI - Hyperglycemia reduces gallbladder emptying and plasma hormone secretion to modified sham feeding and regular feeding. AB - The purpose of this study was to investigate the effect of acute stable hyperglycemia on gallbladder motility, plasma cholecystokinin level and pancreatic polypeptide secretion. Gallbladder emptying in response to modified sham feeding and regular feeding was determined in six healthy subjects on two separate occasions during normoglycemia (serum glucose = 5 mmol/L) and during hyperglycemia (serum glucose = 15 mmol/L). Pancreatic polypeptide secretion was determined as an indirect measure of cholinergic tone. Gallbladder contraction in response to sham feeding during hyperglycemia (9% +/- 2%) was significantly (p < 0.05) reduced compared with that in normoglycemia (22% +/- 1%). During hyperglycemia, gallbladder emptying after meal ingestion (29% +/- 9%) was significantly (p < 0.05) less than that in normoglycemia (60% +/- 10%). Sham feeding did not affect plasma cholecystokinin levels. Regular feeding induced significant (p < 0.05) increases in plasma cholecystokinin levels in both experiments. However, integrated postprandial plasma cholecystokinin secretion was significantly (p < 0.05) reduced during hyperglycemia compared with that in normoglycemia (29 +/- 5 pmol.60 min vs. 58 +/- 10 pmol.60 min). Modified sham feeding-and feeding-stimulated pancreatic polypeptide secretion during hyperglycemia (235 +/- 95 pmol.90 min and 1,035 +/- 267 pmol.60 min, respectively) were significantly (p < 0.05) less than levels seen in normoglycemia (434 +/- 71 pmol.90 min and 1,961 +/- 219 pmol.60 min, respectively). This study indicates that gallbladder emptying and plasma hormone secretion in response to sham feeding and regular feeding are affected by blood glucose levels. PMID- 8514251 TI - Effect of ursodeoxycholic acid on the kinetics of cholic acid and chenodeoxycholic acid in patients with primary sclerosing cholangitis. AB - Treatment of patients with cholestatic liver diseases with ursodeoxycholic acid has been shown to have beneficial effects that may be related to a shift in the balance between hydrophilic and hydrophobic bile acids in favor of hydrophilic bile acids. During treatment of patients with primary sclerosing cholangitis with ursodeoxycholic acid, plasma concentrations of some endogenous bile acids decrease. To test whether the changes in plasma bile acids are due to decreases of their pool sizes or synthesis rates, we determined bile acid kinetics of cholic and chenodeoxycholic acid in six patients with primary sclerosing cholangitis, of whom four also had ulcerative colitis. All patients were studied before and 3 mo after the start of ursodeoxycholic acid treatment. Six healthy subjects served as controls. In patients with primary sclerosing cholangitis, pool sizes of cholic and chenodeoxycholic acid were considerably smaller than those in healthy controls; after ursodeoxycholic acid treatment they were unchanged. Fractional turnover and synthesis of cholic acid increased significantly after ursodeoxycholic acid administration. Fractional turnover of chenodeoxycholic acid also increased significantly, whereas synthesis of this bile acid was unchanged. Our data indicate that in patients with primary sclerosing cholangitis, pool sizes of bile acids are reduced. The decrease of levels of endogenous bile acids in plasma under ursodeoxycholic acid treatment despite unchanged bile acid pool sizes indicates redistribution of the bile acids into the enterohepatic circulation, probably because of improved hepatic clearance after ursodeoxycholic acid treatment. PMID- 8514252 TI - Evaluation of structural change in diffuse liver disease with frequency domain analysis of ultrasound. AB - To evaluate structural changes in diffuse liver disease, frequency domain analysis was applied to ultrasonic signals from the liver. We assumed that liver tissue is a collection of semiregularly arrayed small scatterers of ultrasound. We applied cepstral analysis to the ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum caused by an interference effect among liver scatterers of a given spacing. Patients with liver conditions involving nonspecific change (n = 6), chronic hepatitis (n = 11), cirrhosis (n = 7) or fatty liver (n = 6) were examined. One hundred ultrasonic signals were obtained noninvasively with a 3.5-MHz transducer, and the space among scatterers was calculated for each signal using cepstrum analysis. Two statistical parameters, mode and kurtosis, were determined from the distribution of the space among scatterers for each patient; these parameters were compared with the histological findings in the liver. Space among scatterers kurtosis decreased with progress of liver fibrosis, and space among scatterers mode increased in cirrhosis. Neither space among scatterers kurtosis nor space among scatterers mode was affected by pathological fat in the liver. These results suggest that we can evaluate fibrotic changes in diffuse liver disease and that we can also noninvasively discriminate diffuse fibrotic liver disease from fatty liver. PMID- 8514253 TI - Hepatic 60-kD heat-shock protein responses in alcoholic hepatitis. AB - The precise mechanism of the pathogenesis of alcoholic hepatitis is unknown, but immune involvement may perpetuate and exacerbate the process. Heat-shock proteins, normally protective, may be immunogenic and have been shown to induce antibody formation in some inflammatory conditions. Alcohol, cellular hypoxia and tumor necrosis factor, all involved in alcoholic hepatitis, are potent inducers of heat-shock protein. In this study, we sought 60-kD heat-shock protein in liver tissue with a murine monoclonal antibody and measured circulating antibody to 60 kD heat-shock protein on ELISA. Fourteen of 20 livers from patients with acute alcoholic hepatitis expressed 60-kD heat-shock protein in hepatocyte cytoplasm in a diffuse pattern with superimposed clusters; other cell types were occasionally positive. Twelve of these patients had high-titer IgA 60-kD heat-shock protein antibody in serum. In contrast, 60-kD heat-shock protein was identified in only 2 of the 10 patients with alcoholic cirrhosis without hepatitis (p = 0.013). These two patients had severe liver disease, and one patient in this group was seropositive for IgA 60-kD heat-shock protein antibody. Eight alcoholic patients with fatty liver alone were negative for antigen, and all but one were negative for antibody. The 10 patients without liver damage were negative for antigen and antibody. The findings that 60-kD heat-shock protein is present in liver tissue of patients with acute alcoholic liver damage and that circulating IgA 60-kD heat shock protein antibody levels are increased may point to one pathogenetic mechanism underlying development and progression of liver damage in alcoholic hepatitis. PMID- 8514254 TI - Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells. AB - Hepatocyte growth factor is the most potent mitogen known for hepatocytes, and increasing evidence suggests that hepatocyte growth factor plays an important role in liver regeneration. However, hepatocytes are not the only liver epithelial cell population that proliferates during regeneration. Experimental and clinical data indicate that the regenerative liver response also includes the participation of nonparenchymal epithelial cells. The possible role of hepatocyte growth factor in this nonparenchymal epithelial cell regenerative response has not been explored. We studied the effects of hepatocyte growth factor with a model of two normal mouse nonparenchymal epithelial cell-derived cell lines with varying differentiation potentials. Addition of hepatocyte growth factor induced mitogenesis and scattering of colonies growing on culture dishes in both cell lines. Furthermore, hepatocyte growth factor was found to exert a profound morphogenic effect on cells growing in collagen matrixes. Hepatocyte growth factor-treated embryonic BNL CL.2 cell colonies developed elaborately branching elongated cords with only minimal tubularization. Hepatocyte growth factor treated postnatal NMuLi cell colonies developed a network of anastomosing tubules with wide lumens. These morphological changes were not inhibitable by transforming growth factor-beta and were not induced by other hepatocellular growth factors including epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor and insulin. Histological sections of the hepatocyte growth factor-treated BNL CL.2 cell colonies resembled neocholangioles, believed to include facultative stem cells, which proliferate after submassive and massive hepatic necrosis. Sections of hepatocyte growth factor-treated NMuLi colonies resembled ductules proliferating in biliary tract obstruction from a wide variety of causes. This work represents the first examples of hepatocyte growth factor-induced mitogenesis, scattering and morphogenesis in the same cell lines. More important, our data suggest that hepatocyte growth factor mediates liver response to injury not only by acting on hepatocytes but also by exerting mitogenic and morphogenic influences on nonparenchymal epithelial cell components. PMID- 8514255 TI - The role of 16,16-dimethyl prostaglandin E2 on the intrahepatic biliary branches in dogs. AB - We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 +/- 9.0 (mean +/- S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 +/- 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2. PMID- 8514256 TI - Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha. AB - The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for successful liver regeneration and complete recovery from liver injury. Hence disruption of intercellular regenerative signaling may contribute to the pathogenesis of chronic alcoholic liver disease. To test this hypothesis, the cytokine and regenerative responses triggered by partial hepatectomy were compared in ethanol-fed rats and isocalorically maintained, pair-fed controls. To further clarify the effect of ethanol on tumor necrosis factor-modulated regenerative effects, we evaluated some of the rats in each feeding group after pretreatment with antibodies to tumor necrosis factor. As expected, ethanol inhibited DNA synthesis and liver cell proliferation after partial hepatectomy. Ethanol-associated inhibition of liver regeneration occurred despite apparently similar serum concentrations of the tumor necrosis factor-inducible cytokine interleukin-6. Treatment with antibodies to tumor necrosis factor 1 hr before partial hepatectomy inhibited post-partial hepatectomy induction of interleukin-6 and liver regeneration in ethanol-fed and pair-fed rats. However, serum interleukin-6 was reduced more in ethanol-fed rats than in control rats (93% vs. 66%; p < 0.05). Antibodies to tumor necrosis factor also inhibited hepatic DNA synthesis more in ethanol-fed rats than in controls (85% vs. 50%; p < 0.05). In ethanol-fed rats, the increased effect of tumor necrosis factor antibody on post partial hepatectomy DNA synthesis suggests heightened sensitivity of hepatocytes to tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514257 TI - Mechanism of biliary lipid secretion in the rat: a role for bile acid-independent bile flow? AB - Bile acid-induced lipid secretion was compared in unanesthetized normal control and Groningen Yellow Wistar rats during variations in endogenous bile acid output. Groningen Yellow rats express a genetic defect in the biliary secretion of various organic anions. During a 5-hr period after interruption of the enterohepatic circulation, bile acid secretion decreased from 36.4 +/- 1.8 to 1.9 +/- 0.3 mumol per 30 min in normal control rats and from 37.1 +/- 2.8 to 1.8 +/- 0.2 mumol per 30 min in Groningen Yellow rats, respectively (mean +/- S.E.M., n = 5). The relationship between bile acid secretion and bile flow showed similar slopes (normal control, 8.74 +/- 0.44 microliter/mumol and Groningen Yellow rats, 7.71 +/- 0.42 microliter/mumol) but different y-intercepts (normal control, 243 +/- 8 and Groningen Yellow, 127 +/- 4 microliters per 30 min; p < 0.001), corresponding to a 47% reduction of the bile acid-independent fraction of bile flow in Groningen Yellow rats. During the course of the experiment, the ratio of lipids (phospholipids plus cholesterol) to bile acids increased in both strains more than threefold but was permanently higher in Groningen Yellow than in normal control rats (p = 0.035), implying that Groningen Yellow rats continuously secreted more lipid per bile acid. No differences in bile acid pool composition or in bile canalicular membrane composition and fluidity between the two strains were detected. The results indicate that apart from previously demonstrated factors (bile acid concentration, bile acid composition and hydrophilic organic anion concentration in bile), another parameter affects the efficacy of bile acids to induce biliary lipid secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514258 TI - Bacterial translocation in acute and chronic portal hypertension. AB - Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation at two stages of experimental portal hypertension: (a) acute (when shunting is minimal); and (b) chronic (when shunting is extensive and mimics the portal hypertension of cirrhosis). Rats were killed 2 days (acute) or 15 days (chronic) after partial portal vein ligation or control surgeries. Samples of mesenteric lymph nodes, blood, liver and spleen for standard bacteriological cultures and a fragment of ileum for histological examination were obtained. Two days after surgery, a significantly greater proportion of rats with acute portal hypertension (12 of 13 or 92%) had positive mesenteric lymph node cultures compared with both control groups: sham-operated (4 of 13 or 31%) and inferior vena cava-ligated (3 of 10 or 33%) animals (p < 0.01). However, 15 days after surgery no differences in translocation to mesenteric lymph nodes were found between rats with chronic portal hypertension (3 of 15 or 20%) and sham-operated controls (3 of 11 or 27%). In neither the acute nor the chronic rats were bacteria isolated from blood, spleen or liver. Rats with acute portal hypertension had significantly greater mesenteric inflammation than rats with chronic portal hypertension and control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514259 TI - Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat. AB - The present study defines the origin of cholesterol subserving bile acid synthesis in male rats with an extracorporal bile duct by labeling newly formed cholesterol with tritiated water. Within 6 hr after interruption of the enterohepatic circulation, the bile acid pool was depleted. At this early time point the proportion from de novo cholesterol was 8% and 12% for biliary cholesterol and cholate, but 18% and 19% for muricholate and chenodeoxycholate, respectively. This proportion gradually rose to 40%, 34%, 51% and 51%, respectively, at 15 to 30 hr. At 78 hr after bile diversion, 64% of cholate was labeled, compared with 84% to 88% of the other biliary lipids and 71% of plasma cholesterol. Total and labeled bile acid secretion exhibited the same diurnal rhythm. To allow differentiation between direct hepatocytic de novo synthesis of bile acids from acetate and recycling of labeled plasma cholesterol, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (pravastatin) was infused from 54 to 78 hr. It suppressed total synthesis of primary bile acids by 60% to 80% but decreased the tritium label of bile acids only from a range of 74% to 92% (54 hr) to a range of 54% to 63% (78 hr), which was in the range of plasma cholesterol (58%). We conclude that bile acids and biliary cholesterol are synthesized mostly from preformed (i.e., plasma) cholesterol, both immediately after depletion of the pool in enterohepatic circulation and after derepression. Moreover, the hepatic cholesterol pools subserving the synthesis of different bile acids and biliary cholesterol secretion are not identical. PMID- 8514260 TI - Blood-brain barrier permeability is markedly decreased in cholestasis in the rat. AB - The blood-brain-barrier plays an essential role in regulating the entrance of substances into the brain. To date, permeability of the blood-brain barrier has not been studied in models of cholestatic liver injury, although levels of substances known to enhance vascular permeability (bile acids, substance P, histamine) are elevated in cholestasis. Two rat models of cholestasis were studied: bile duct resection (5 days after surgery) and alpha naphthylisothiocyanate treatment (45 mg/kg/day for 7 days). The mean value for whole brain blood-to-brain transfer constant in bile duct resection rats was about 50% less than corresponding values in sham-operated and unoperated control rats (p < or = 0.05, respectively). Reductions in blood-to-brain transfer constant of similar magnitude were found in the caudate nuclei, cortexes and hippocampi of bile duct-resected rats. Blood-to-brain transfer constant values in alpha-naphthylisothiocyanate-treated rats were also about 50% less in whole brain and specific brain regions than corresponding control values. A precedent for a decrease in blood-to-brain transfer constant is the dexamethasone-treated rat, in which the phenomenon has been attributed to a decrease in cerebral capillary endothelial cell membrane fluidity. We confirmed that blood-to-brain transfer constant values are reduced by about 50% in dexamethasone-treated rats. A decrease in membrane fluidity affords a rational explanation for a decrease in blood-to-brain transfer constant in cholestasis as a consequence of the dynamic equilibrium between elevated plasma levels of cholesterol in cholestasis and cell membranes exposed to the circulation. PMID- 8514261 TI - Differences in the steady-state levels of c-fos, c-jun and c-myc messenger RNA during mitogen-induced liver growth and compensatory regeneration. AB - The steady-state levels of c-fos, c-jun and c-myc messenger RNA were investigated in rat liver tissue after proliferative stimuli of different nature-namely, compensatory regeneration induced by partial hepatectomy or carbon tetrachloride administration-and direct hyperplasia induced by four different hepatomitogens: lead nitrate, ethylene dibromide, cyproterone acetate and nafenopin. We show here that whereas c-fos and c-jun expression increased soon after partial hepatectomy or carbon tetrachloride administration, an increased expression of c-jun in the absence of c-fos expression occurred during direct hyperplasia induced by lead nitrate and ethylene dibromide. When hyperplasia was induced by cyproterone acetate and nafenopin, the mitogenic response of the liver was not associated with an increased expression of c-jun or c-fos, despite the fact that the timing of the cell cycle was similar to that observed after partial hepatectomy. Finally, when c-myc expression was analyzed, it was found that proliferative conditions associated with an increased expression of this gene were characterized by an increased expression of c-jun. On the contrary, the hyperplasia induced by cyproterone acetate and nafenopin, which is characterized by a lack of increase in the expression of c-fos and c-jun, was also not associated with an increased c-myc expression. Similar results were obtained in these experiments with the mitogen nafenopin, a peroxisome proliferator. In fact, liver hyperplasia induced by this compound was not preceded or accompanied by an increased expression of c-fos and c-myc. This study suggests that depending on the nature of the proliferative stimulus, an increased expression of c-fos, c-jun and c-myc may not be necessary for in vivo induction of liver cell proliferation. PMID- 8514262 TI - Reduction of cerebral perfusion precedes rise of intracranial pressure in rats with ischemic fulminant liver failure. AB - In fulminant liver failure, brain edema may progress to intracranial hypertension. However, the rise in intracranial pressure is a late event in this sequence. We investigated the relationship between cerebral perfusion and development of intracranial hypertension in a well-characterized model of fulminant liver failure, the rat subjected to hepatic devascularization (n = 11). In addition, we examined the effects of hyperglycemia on the development of brain edema because high blood glucose level can exacerbate other forms of brain edema, as seen in stroke. Intracranial pressure was continuously monitored with a cisterna magna catheter; relative changes in blood flow were continuously assessed with a Doppler flow probe on the internal carotid artery. Cerebral perfusion decreased by 62%, with the greatest reduction before the onset of increased intracranial pressure. Intracranial pressure did not change until 2 hr before death, at which time it increased exponentially. Brain water in fulminant liver failure rats was significantly increased compared with that in controls. Hyperglycemia (200 to 220 mg/dl) had no effect on time elapsed until loss of corneal reflex, percentage of brain water, maximal intracranial pressure or pattern of change in cerebral perfusion compared with euglycemia (80 to 100 mg/dl). Sham-operated animals showed no changes in measured parameters. We conclude that a linear reduction in cerebral perfusion precedes the rise of intracranial pressure in this model, a decrease that may reflect changes in brain metabolic activity at the time that brain edema develops. Carotid blood flow monitoring may be a useful noninvasive tool for the detection of cerebral events in fulminant liver failure. PMID- 8514263 TI - Incidence of adverse reactions to cyclosporine after liver transplantation is predicted by the first blood level. AB - Despite the availability of whole-blood cyclosporine assays, the different responses of individual patients to its administration after transplantation continue to pose clinical problems, particularly with respect to toxicity. Fifty seven recipients of first orthotopic liver transplants were studied between January 1992 and July 1992. Initial immunosuppression was carried out with azathioprine, methylprednisolone and cyclosporine, at a dose of 1 mg/kg/day adjusted to achieve blood levels between 400 and 600 ng/ml. Cyclosporine levels were measured 12 hr after the start of intravenous administration and correlated with the occurrence of toxic complications. Twelve patients experienced toxic complications in the first 7 days after orthotopic liver transplantation. These were neurological in six patients (of whom four also had kidney failure) and renal complications in the other six patients. All complications were reversed by reducing or stopping administration of cyclosporine. We noted excellent correlation between the occurrence of complications and cyclosporine whole-blood levels (p < 0.0001) despite the fact that levels did not exceed the therapeutic range. However, no correlation was observed between toxicity and cumulative dosage. In this study we were able to demonstrate that a standardized dose of cyclosporine does not prevent the occurrence of toxic side effects even when cyclosporine whole-blood levels are subsequently maintained in the therapeutic range. This highlights the importance of the first dose of cyclosporine and consequent early postoperative blood levels and indicates that these problems are unlikely to be overcome until a method of predicting individual requirements can be established in clinical practice. PMID- 8514265 TI - Donor-derived chimerism in recipients of organ transplants. PMID- 8514266 TI - Idiopathic portal hypertension. PMID- 8514267 TI - Artificial liver: a forthcoming attraction. PMID- 8514264 TI - Cell migration and chimerism after whole-organ transplantation: the basis of graft acceptance. PMID- 8514268 TI - Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors. AB - Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post transplant periods is ineffective, presumably because of decreased T cell dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody-positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell-depleted bone marrow cells from hepatitis B-immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B-immune donors to immunosuppressed recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514269 TI - Excess HBcAg in HBc antibody-negative chronic hepatitis B virus carriers. AB - HBcAg and antibody to HBcAg were assayed in chronic hepatitis B virus carriers who were not reactive for HBc antibodies on available commercial tests. HBc antibody-negative sera, collected before the onset of the acute phase in recovering patients, were used as controls. A high level of HBcAg was detected in HBc antibody-negative chronic hepatitis B virus carriers after dissociative treatment. HBcAg levels were correlated with serum hepatitis B virus DNA levels. Precipitation of immune complexes increased the amount of detected HBcAg. HBc antibodies were detected in some patients only after sucrose gradient fractionation of serum and dissociative treatment. All HBsAg-positive chronic carriers who lacked HBc antibody were immunocompromised. Our results show that in HBc antibody-negative chronic hepatitis B virus carriers with active replication, HBc antibodies may be complexed by the excess of antigen and become undetectable by the available commercial tests. Unresponsiveness to HBcAg cannot always be ascribed to infection by another hepatitis B virus-related virus or hepatitis B virus variant. PMID- 8514270 TI - Differential depletion of carotenoids and tocopherol in liver disease. AB - Carotenoids and tocopherols are major natural protective agents against free radical-mediated liver damage, but their levels in diseased liver are largely uncharted. Therefore we carried out measurements with high-pressure liquid chromatography of alpha- and beta-carotene, lycopene, cryptoxanthin, lutein and zeaxanthin, total retinoids and alpha- and gamma-tocopherol. Liver tissue was obtained from percutaneous needle biopsies, livers of transplant recipients or a donor bank. Compared with controls (transplant donors; n = 13), levels of all carotenoids and retinoids were extremely low at all stages of liver disease. Patients with alcoholic cirrhosis (n = 11) had 20- and 25-fold decreases of levels of lycopene (p < 0.001) and alpha- and beta-carotene (p < 0.005), respectively. Even in subjects with less severe alcoholic liver disease (steatosis, perivenular fibrosis, portal fibrosis; n = 14) and in patients with nonalcoholic liver disease (n = 13), levels were four to six times lower than those in normal subjects. By contrast, levels of alpha-tocopherol were decreased significantly only in patients with cirrhosis, who displayed a threefold reduction. In the serum of most patients, lycopene and tocopherol concentrations were not depressed, whereas one third of alpha- and beta-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver alpha- and beta-carotene levels (p < 0.0001; r = 0.715). However, of the patients with extremely low liver alpha- and beta carotene concentrations, more than half had blood levels in the normal range, suggesting that liver disease interferes with the uptake, excretion or, perhaps, metabolism of alpha- and beta-carotene. In the cirrhotic livers of eight candidates for liver transplantation, the ratios of alpha- and beta-carotene to total retinoids and of beta-carotene to retinoids were much higher than those in normal livers, suggesting some impairment in the conversion of alpha- and beta carotene to retinoids. In most cases, even with high ratios, absolute levels of hepatic alpha- and beta-carotene and retinoids were severely depressed. We concluded that, even in the presence of normal serum levels alpha- and beta carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels. PMID- 8514271 TI - Passage of amino acids and glucose across the blood-brain barrier in patients with hepatic encephalopathy. AB - We repeatedly measured blood-brain barrier passage of phenylalanine, leucine, glucose and GABA in nine patients with hepatic encephalopathy using the intravenous double-indicator technique. Controls were four patients without liver disease and two of the patients who had recovered completely from their hepatic encephalopathy. The corrected cerebral venous output curves were fitted by use of a three-compartment model with four parameters. In the patients with hepatic encephalopathy, the permeability-surface area products for phenylalanine and leucine from the blood to the brain and from the brain interstitial fluid to the intracellular compartment, the unidirectional extraction and the brain amino acid influx were similar in the two groups. The permeability from the brain back to blood for phenylalanine was decreased by 72% in patients with hepatic encephalopathy compared with that in the control group (p < 0.05), whereas no difference was seen for leucine. The permeability from the brain back to the blood for phenylalanine decreased with coma grade and normalized in the two patients who recovered. Correspondingly, the calculated brain interstitial fluid concentration of phenylalanine was increased in the patients with hepatic encephalopathy. The transfer variables for blood-brain barrier passage of glucose were similar in the two groups. The permeability from the blood to the brain for GABA was very low in both the patients with hepatic encephalopathy and the control group. We conclude that in hepatic encephalopathy the permeability from brain to blood for phenylalanine decreases with coma grade. The decrease is caused by an increased interstitial fluid concentration of the amino acid. No evidence was found of general or selective blood-brain barrier disturbance in hepatic encephalopathy. PMID- 8514272 TI - Magnetic resonance imaging and different levels of iron overload in chronic liver disease. AB - The need for accurate and noninvasive evaluation of liver iron stores prompted us to evaluate the reliability of high-field magnetic resonance imaging equipment in liver patients with low or moderate siderosis, given the poor results obtained using systems operating at low field strength in such cases. Twenty patients with sporadic porphyria cutanea tarda and 28 with comparable chronic liver diseases (chronic hepatitis or cirrhosis) and moderate siderosis were compared with 10 patients with idiopathic or secondary hemochromatosis and 10 healthy controls. Plasma iron profile, ferritin concentration and liver iron concentration, determined with atomic absorption spectroscopy, were matched with the magnetic resonance parameters-namely, transverse relaxation time and the signal intensity for a given proton amount, obtained with equipment operating at a field strength of 1.5 T. Hemochromatosis patients with mean liver iron concentrations of 550 mumol/gm dry wt (vs. 10 mumol of controls) exhibited an impressive reduction in the signal intensity with respect to the other three groups, and this reduction prevented any further comparison with the same porphyria cutanea tarda and chronic liver disease groups, whose liver iron level was twice that of the controls. The signal intensity remained almost unchanged in the latter groups, whereas the transverse relaxation time was significantly reduced. Moreover, correlation with liver iron was significantly inverse in the case of the transverse relaxation time (n = 17, r = 0.62, p = 0.008) and direct in the case of the transverse relaxation rate. The transverse relaxation time values returned to normal in five patients who had completed an iron-depletion program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514273 TI - Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification. AB - A total of 41 non-cutaneous peripheral T-cell lymphomas were classified following the updated Kiel classification. Of these, 20 cases belonged to the low-grade group (T-cell chronic lymphocytic leukaemia, 3; lymphoepithelioid, 5; angioimmunoblastic, 4; pleomorphic small cell, 8) and 21 to the high grade group (pleomorphic medium and large cell, 11; immunoblastic, 3; large-cell anaplastic Ki-1 positive, 7). Seventy per cent showed a CD4+/CD8-phenotype, 39% a defective phenotype and 88% an activation phenotype. Eighty per cent had B-symptoms, 63% hepatomegaly, 48% splenomegaly and 26% had involvement of more than three lymphoid areas. Bone marrow was infiltrated in 34%, central nervous system in 4%, lung in 12% and skin in 14.6%. Seventeen per cent presented with extranodal disease and 82.8% had stage III/IV disease. Hypergammaglobulinaemia was found in 29%, hypercalcaemia in 7%, raised LDH serum levels in 58% and HTLV-I antibodies in only one case. Of the 37 treated patients 18 (48%) achieved a complete remission, but 33% relapsed. Mortality was 59% and actuarial overall survival at 38 months was 0.32. In the comparison of the clinical, analytical and immunophenotypic variables and outcome between low and high grade groups, only the average of bone marrow infiltration in the low grade and stage I-II, presence of defective phenotypes and higher Ki-67 positivity in the high grade group were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514274 TI - Heterogeneity of CD3 antigen expression in T-cell lymphoma. AB - CD3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. We identified 40 cases in which CD3 was present on only a proportion of the neoplastic cells. This phenomenon of heterogeneous CD3 expression was commonest in pleomorphic T-cell lymphomas (22/42 cases) and in CD30 (Ki-1)-positive lymphomas (5/11 cases), and was less frequently observed in mycosis fungoides (4/18 cases) and not seen in T-cell lymphoblastic lymphoma (0/9 cases). CD3 expression was often related to cell morphology, with CD3 antigen being present on the smaller neoplastic cells but absent from the larger ones. The diagnostic significance of these observations is that, on occasion, it may be possible to diagnose a lymphoma as being of T-cell origin in paraffin sections by demonstrating a minor subpopulation of CD3-positive neoplastic cells. PMID- 8514275 TI - Chronic hepatitis in multiple virus infection: histopathological evaluation. AB - The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty-nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The delta-virus (HDV) was not associated with severe necro-inflammatory lesions, but HDV-positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non-specific for HCV infection, or that these cases represent HCV infection with false-negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear. PMID- 8514276 TI - Solitary myofibroma in adults: clinicopathological analysis of a series. AB - Solitary myofibroma is a recently described, benign neoplasm of superficial soft tissue, which represents the adult counterpart of infantile myofibromatosis and is poorly recognized. Eleven new cases are presented herein. The patients were mostly adults with ages ranging from 13-64 years. They presented with a solitary, usually painless nodule of variable duration in the skin or oral cavity. Histologically, each lesion had a biphasic pattern with spindle cells forming fascicular or whorled areas and rounded, more primitive cells arranged around small vessels, forming haemangiopericytoma-like areas. The characteristic zonation of infantile myofibromatosis was often less marked in adult lesions and there was a haphazard arrangement of the fascicular and pericytic areas in some cases. Hyalinization, especially of the peripheral spindle-celled areas, was frequent. Immunohistochemically, the spindle cells were desmin negative but muscle actin (HHF-35 and IA4) positive. The rounded cells were both desmin and actin negative. Electronmicroscopy confirmed the myofibroblastic/fibroblastic nature of tumour cells in two cases. Although vascular invasion was seen in two cases, solitary adult-type myofibroma pursues a benign clinical course. PMID- 8514277 TI - Expression of tumour necrosis factor-alpha in cryptogenic fibrosing alveolitis. AB - We have studied 15 cases of cryptogenic fibrosing alveolitis stained with a monoclonal antibody reactive with human tumour necrosis factor-alpha (TNF alpha), a cytokine that has been implicated in inflammation and fibrosis. Seven were examples of lone cryptogenic fibrosing alveolitis and eight were examples of cryptogenic fibrosing alveolitis in patients with systemic sclerosis. There was widespread staining of epithelial cells, particularly hyperplastic type II pneumocytes. Macrophages stained only weakly. In a control group of 10 patients dying of unrelated conditions, staining for TNF alpha was weak and, in the alveolar epithelium, was confined to a very occasional type II pneumocyte. The strong expression of TNF alpha in hyperplastic type II pneumocytes suggests that TNF alpha produced during alveolar epithelial regeneration may play a part in the fibrosis seen in this disease. PMID- 8514278 TI - Detection of the Ki-67 antigen in fixed and wax-embedded sections with the monoclonal antibody MIB1. AB - Novel antibodies have been generated by immunizing with bacterially expressed fragments of the repetitive motif of the Ki-67 gene. One such antibody, MIB1, recognizes a fixation and embedding resistant epitope on the Ki-67 protein if sections are previously microwaved in a citrate buffer. We have investigated the utility of this antibody as a marker of cell proliferation in archival material. The microwave technique is simple but requires careful monitoring since different tissues and fixatives require different irradiation times. Strong nuclear immunoreactivity was detected with all fixatives studied. Cytoplasmic staining was not identified. In a wide range of normal tissues the distribution and number of MIB1 immunoreactive cells matched that of cryostat sections stained with Ki 67. In nude mouse xenografts in which the growth fraction had been defined using a fraction of labelled mitosis method, the labelling index with MIB1 matched that previously determined for Ki-67 and correlated well with the growth fraction. Other markers of proliferation (e.g. proliferating cell nuclear antigen) have been shown to be expressed in DNA repair, thus we investigated expression of MIB1 immunoreactivity in situations of DNA repair in vivo--ultraviolet irradiated human skin. MIB1 staining correlated with semi-conservative DNA synthesis rather than excision repair DNA synthesis. Finally, the morphological and cell cycle distribution of MIB1 expression is identical to that of Ki-67. Thus, MIB1 represents a new anti-Ki-67 antibody which appears to be a robust marker of cell proliferation easily applicable to archival material. PMID- 8514279 TI - The histopathology of transcervical resection of the endometrium: an analysis of 200 cases. AB - The results of a series of 200 patients treated by transcervical resection of the endometrium are presented. The failure rate was 20% with a minimum follow up period of 18 months, although seven women (3.5%) had treatment beyond this interval. A second resection was performed in 14 patients with two later requiring a hysterectomy. An additional 26 women proceeded to hysterectomy following the initial resection. Specimen weight was inversely related to the need for further surgery with no secondary operations performed when more than 12 g of endometrium and myometrium had been resected. Age was also correlated with clinical outcome with patients under 35 years of age more likely to require further operative treatment. No histological feature could be identified which predicted failure of the procedure. The main role for histopathological assessment of transcervical resection specimens is in the provision of an accurate weight and the identification of the relatively rare cases harbouring endometrial or myometrial malignancy. Although endometrial resection appears to have resulted in fewer hysterectomies in the treatment of dysfunctional uterine bleeding, long-term follow-up is required before an accurate assessment of success can be established. PMID- 8514280 TI - Signet ring cell differentiation in adenocarcinoma of the prostate: a study of five cases. AB - Signet ring cell differentiation in adenocarcinoma of the prostate is uncommon. In a review of 200 cases of prostatic carcinoma, we identified five cases with this change, all in moderately to poorly differentiated prostatic carcinomas. The signet ring cells in prostatic carcinoma contain an intracytoplasmic lumen, shown on electronmicroscopy to be lined by microvilli. Transition stages were seen from solid to acinar to signet ring cells to mucinous variants. We believe that this change is part of the spectrum of appearances of prostatic carcinoma and should not be regarded as a subtype of specific significance. PMID- 8514282 TI - An unusual case of retroperitoneal seminoma and fatal peliosis of the liver. AB - We report an unusual case of fatal peliosis of the liver, spleen and lymph nodes in a 37-year-old man who had previously been treated for retroperitoneal seminoma with surgery and radiotherapy. The current hypotheses for the pathogenesis of peliosis are reviewed and discussed. PMID- 8514281 TI - Immunohistochemical markers of carcinoma in situ of the testis also expressed in normal infantile germ cells. AB - Carcinoma in situ of the testis is an intratubular, pre-invasive lesion preceding germ cell tumour. In adult men, carcinoma in situ cells differ in several aspects from normal germ cells. For example, placental-like alkaline phosphatase and/or the epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1-60 are not seen in normal germ cells, whereas their presence is considered a specific sign of carcinoma in situ. As it is known that placental-like alkaline phosphatase and the epitope for TRA-1-60 are expressed in normal fetal germ cells it is possible that the markers could appear in normal infantile germ cells in a period after birth before they lose their expression. In children, carcinoma in situ cells may be difficult to identify morphologically and the use of the markers could be of great value. However, little information is available on the expression of the markers of adult carcinoma in situ in normal infantile germ cells. We investigated gonads from 66 boys less than 15 years old who died suddenly. Their deaths were unrelated to testicular disease. Immunohistochemical staining with anti-placental-like alkaline phosphatase antibody and monoclonal antibodies TRA-1 60 and 43-9F were performed. We found that these markers were expressed in some normal infantile germ cells until the age of 1 year. Therefore, these markers are not suitable for diagnosis of carcinoma in situ during the early postnatal period of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514283 TI - The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non asbestos-associated mesotheliomas. AB - It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure. PMID- 8514284 TI - Isolated cranial granuloma induced by Pneumocystis carinii. PMID- 8514285 TI - Soft tissue ependymoma: a report of three cases. PMID- 8514286 TI - Epididymal cavernous haemangiomas. PMID- 8514287 TI - Recurrent duodenal gangliocytic paraganglioma with lymph node metastases. PMID- 8514288 TI - Inflammatory fibroid polyps in Crohn's disease. PMID- 8514289 TI - Of spots, stripes and muddled thinking! PMID- 8514290 TI - Cribriform intra-tubular epididymal change. PMID- 8514291 TI - Sarcoidosis of the testis. PMID- 8514292 TI - Nasopharyngeal and nasal malignant lymphoma. PMID- 8514293 TI - Self-incrimination on medical board and licensing applications. PMID- 8514294 TI - The biopsychosocial legacy of deinstitutionalization. PMID- 8514295 TI - Modifying the impact of managed care. PMID- 8514296 TI - Opportunities for improving community mental health services for elderly persons. PMID- 8514297 TI - On being very smart: the mental health community's response in the health care reform debate. AB - President Clinton's proposal for a health care system based on managed competition began a dialogue within the mental health community about whether such a system would work in the mental health area. In early March a large coalition representing more than 30 mental health organizations, including advocacy organizations, state systems, professional associations, provider agencies, families, and consumers, formally transmitted to the President's Task Force on National Health Care Reform a document presenting a unified position on how mental health care should be delivered within a reformed health care system. The consensus document, reproduced here, maintains that a full range of services must be available to all children and adults with mental or emotional disorders. The document presents guidelines for containing costs, for standards of delivery for mental health services, and for the role of the states and the federal government within the new health care system. PMID- 8514298 TI - The case for a services-based approach to payment for mental illness under national health care reform. AB - In this position paper drafted by the committee on psychopathology of the Group for the Advancement of Psychiatry, the authors discuss merits and disadvantages of three different approaches to equitable coverage of mental illness: coverage for selected psychiatric diagnoses, coverage based on severity of impairment, and coverage of services. They believe that coverage of selected disorders has political appeal but is discriminatory and arbitrary; it is also impractical because clinicians may overdiagnose conditions covered by insurance and underdiagnose excluded conditions. Coverage based on severity of impairment, or disability, has similar limitations. The authors believe services should be the principal basis for coverage, as under general medical insurance. The approach is nondiscriminatory, and costs can be controlled through such means as managed care, changes in the payment system, or benefit design. PMID- 8514299 TI - Ensuring services for persons with chronic mental illness under national health care reform. AB - People with chronic mental illness present complex challenges for the design of health care financing reforms. In this position statement from the committee on psychiatry and community of the Group for the Advancement of Psychiatry, the authors describe chronic and severe mental illnesses as psychiatric illnesses that require acute and ongoing psychiatric assessment and treatment, as chronic medical diseases that require ongoing rehabilitative services, and as persistent disabilities that need ongoing supportive care and social services. Any proposal for health care reform must ensure parity of chronic psychiatric illnesses with other psychiatric conditions. It must also reimburse psychiatric rehabilitation at parity with other medical rehabilitation and provide equal access to and reimbursement for broad ancillary health services that reduce costs and improve quality of life. PMID- 8514300 TI - Investor-owned psychiatric hospitals and universities: can their marriage succeed? AB - Economic and competitive pressures have spurred a growing number of affiliations between university medical centers and for-profit health care corporations. University facilities can benefit from such partnerships through strengthened financial support, increased marketing and administrative expertise, and economies of scale. The university connection gives the investor-owned hospital enhanced status, sends a message of clinical excellence, and involves the hospital in educational and research programs that aid in physician recruitment and further enhance its reputation. However, the university's goals of education, research, and public service are not always compatible with the investor-owned hospital's goal of maximizing profits. The authors review the benefits and problems that result from affiliations between university medical centers and investor-owned corporations and discuss principles to be considered in structuring such partnerships. PMID- 8514301 TI - An integrative ideology to guide community-based multidisciplinary care of severely mentally ill patients. AB - Most practitioners working in community support settings understand the need to provide a comprehensive array of well-coordinated services to individuals with severe mental disabilities. However, a lack of consensus about the conceptual basis of mental health care, especially between advocates of psychosocial rehabilitation and psychiatric practitioners who favor a more medically oriented approach, has hindered efforts to optimize the effectiveness of the multidisciplinary teams found in most community support programs. The authors articulate 18 basic assumptions that have been helpful in their clinical practice in building an integrative ideology among professionals with disparate training and orientations. The assumptions attempt to balance the reality of psychiatric disorders with a fundamental interest in maintaining the autonomy and dignity of people with severe mental disorders. PMID- 8514302 TI - Medication refusal and judicial activism: a reexamination of the effects of the Rivers decision. AB - OBJECTIVE: In 1986 New York State courts in Rivers v. Katz mandated judicial review of cases in which involuntarily hospitalized psychiatric patients formally refuse medications; previously only a clinical-administrative review was required. In an earlier study the authors found that formal refusals of medications declined significantly in the year after the Rivers decision and that length of time between refusal and its resolution increased. To determine whether these effects were maintained over time, data for the second year after the Rivers decision were examined. METHODS: Chi square analysis and analysis of variance were used to compare data from both a private and a state-operated hospital for the year before the Rivers decision with data from the first and second years after. RESULTS: The significant declines in the number of patients formally refusing medications were maintained in the second year after Rivers at both hospitals, as were the significant increases in the length of time to resolution. In the second year, judges continued to uphold the treating psychiatrists' recommendations. The decline in the refusal rates was not found to be part of a broader trend that had been manifest before the Rivers decision. CONCLUSIONS: The sharp decline in refusals resulted in fewer patients having their medications reviewed by others not directly involved in their care. Increased time to resolution has diminished quality of care and has resulted in increased patient decompensation and staff injuries. PMID- 8514303 TI - Family involvement in residential treatment of children with psychiatric disorder and mental retardation. AB - OBJECTIVE: The goals of the study were to determine the extent of family involvement with children in residential treatment settings, to examine whether involvement diminishes over time, and to examine the relationship between involvement and the child's diagnosis as well as the demographic characteristics of the child and the family. METHODS: Staff rated the level and frequency of family involvement with 234 children, aged five to 19 years, living in three residential treatment centers. The children were grouped according to three diagnostic categories: psychiatric disorder, mental retardation, and dual diagnosis of psychiatric disorder and mental retardation. RESULTS: Almost one third of the children had no family contact, and about 50 percent had three or fewer contacts per year. The level of family involvement was lower with dually diagnosed children than with children who had only psychiatric disorder or mental retardation. Level of involvement was also related to the driving time between the family home and the residential facility and to socioeconomic status, variables that seemed to account for the lower level of involvement of families with dually diagnosed children. CONCLUSIONS: Greater distance between the family home and the residential treatment center and low socioeconomic status greatly limit a family's accessibility for involvement with children in out-of-home placements. These obstacles are more likely to occur in families of dually diagnosed children. PMID- 8514304 TI - Substance abuse and onset of psychotic illness. AB - OBJECTIVE: This study examined the relationship of substance abuse history to psychotic diagnosis and clinical presentation in a sample of 188 subjects with newly diagnosed psychotic illness. METHODS: Subjects were assessed using a structured diagnostic interview and clinical rating scales. The diagnosis and demographic and clinical characteristics of subjects with a substance abuse history were compared with those of subjects without a substance abuse history. Data for males and females were considered separately in most analyses. RESULTS: Substance abuse history was unrelated to initial diagnosis, age at onset of psychotic symptoms, ratings of best and worst levels of functioning, or severity of positive symptoms. Substance abuse was significantly associated with higher anxiety and depression scores on the Brief Psychiatric Rating Scale. Males without substance abuse had more negative symptoms and were less likely to have attempted suicide than males with substance abuse. CONCLUSIONS: Substance abuse appears to have limited influence on the clinical presentation of non-substance induced psychotic disorders. PMID- 8514305 TI - A comparison of physically aggressive behavior in two VA nursing homes. AB - OBJECTIVE: To investigate an apparent difference in the prevalence of physically aggressive behavior in two Veterans Affairs (VA) nursing homes, the authors compared ratings by nurses of residents' assaultive behaviors at the beginning and end of two six-month periods in 1987 and 1991. METHODS: The prevalence of assaultive behavior in each of three diagnostic subgroups (neurologic, psychiatric, and medical) at nursing homes A and B was determined using standardized biannual ratings of patients' behavior. Chi square analysis was used to compare prevalence rates and to compare the proportions of nonaggressive patients who were rated as aggressive at the end of each six-month period. RESULTS: Nursing homes A and B were significantly different in the proportions of patients in the three subgroups; facility A had a greater percentage of neurologic and psychiatric patients, and facility B had a greater percentage of medical patients. Both in 1987 and in 1991, the prevalence of assaultive behavior in nursing home A in all three diagnostic subgroups was higher than that in nursing home B, usually by a statistically significant margin. A significantly higher proportion of nursing home A residents in each subgroup who were rated as nonaggressive at the beginning of the two periods were rated as aggressive at the end of each period. CONCLUSIONS: Further studies are needed to learn whether the substantial difference in assaultive behavior resulted from intrinsic characteristics of the facilities' populations or from the qualities of their environments. PMID- 8514306 TI - Characteristics of homeless patients discharged from an intensive placement unit. PMID- 8514307 TI - Diversion of admissions from state hospitals: a reexamination. PMID- 8514308 TI - Compliance of homeless mentally ill persons with assertive community treatment. PMID- 8514309 TI - Recidivism on an acute psychiatric forensic service. PMID- 8514310 TI - Posttraumatic stress disorder in U.S. and Russian veterans. PMID- 8514311 TI - Urine drug screening of patients admitted to a state psychiatric hospital. PMID- 8514312 TI - Comparison of patient and staff surveys of consumer satisfaction. PMID- 8514313 TI - PTSD and cocaine abuse. PMID- 8514314 TI - Adjustment disorder criteria. PMID- 8514315 TI - The need for asylum. PMID- 8514316 TI - A new health care model. PMID- 8514317 TI - Prominent nurses at NIMH. PMID- 8514318 TI - New federal guidelines seek to help primary care providers recognize and treat depression. Agency for Health Care Policy and Research (AHCPR) of the Department of Human Services. PMID- 8514319 TI - The relative efficiency and power of small-pedigree studies of the heritability of a quantitative trait. AB - Methods to determine the proportion of variability manifested by a quantitative trait that is attributable to additive genetic effects are important tools for human population and statistical geneticists. Though traditional methods based on parent-offspring and sib-pair correlations have been well researched, they are being steadily supplanted or complemented by more powerful pedigree-based variance-component techniques. In this paper, a theoretical investigation of the relative efficiency and power of small (i.e., < 10 members) variance-component pedigree designs for heritability estimation is undertaken. The information gain in adding sibs and generations to pedigrees is discussed. Sample size guidelines based on theoretical power functions are offered, as are directions for future research. PMID- 8514320 TI - Search for the chromosomal location of autosomal dominant cerebellar ataxia from Holguin, Cuba: exclusion from candidate regions on chromosome 4 and 11q. AB - A gene locus for autosomal dominant cerebellar ataxia (ADCA) has been found on chromosome 6p and named spinocerebellar ataxia 1. However, linkage exclusion from chromosome 6p and thus locus heterogeneity has been proven in Cuban ADCA, the largest known collective of ADCA patients, probably due to a founder effect. Two chromosomal regions were analyzed for linkage to Cuban ADCA: chromosome 4, since a pericentromeric inversion has been reported in a member of a European ADCA family, and chromosome 11q22-23, since it is known to contain the gene locus for ataxia telangiectasia, the main autosomal recessive disorder of cerebellar degeneration. In neither region was evidence for linkage found. PMID- 8514321 TI - Transferrin C subtypes and myocardial infarction. AB - Transferrin C subtypes were studied in 124 patients who were survivors of myocardial infarction and population controls to test the hypothesis that the TFC2 type is associated with an increased risk for myocardial infarction. The TFC2 type showed, however, only a marginal increase among the patients (p = 0.038), whereas the TF*C3 allele (p = 0.0004) and the types carrying the TFC3 variant, TFC3-1 and C3-2, displayed a highly significant increase (p = 0.0002). PMID- 8514322 TI - Detecting marker inconsistencies in human gene mapping. AB - When an inconsistency occurs in a pedigree, it may not be apparent which individual(s) are causing it. Here, a statistical method is described which identifies individuals most likely to have caused an inconsistency. The method is based on the sum of squared deviations between two predictors of an individual's genotypes: (1) that given an individual's own phenotype, and (2) that given all phenotypes in the pedigree. Extreme deviations between the two arrays (measured in terms of a sum of squares) are interpreted as indicating an inconsistency. The method is applied to a pedigree with an inconsistency in which it is unclear who is causing the inconsistency. PMID- 8514323 TI - The Y-specific p21A1/TaqI polymorphism occurs in four major population Oroups. AB - The p21A1/TaqI polymorphism was studied in 904 individuals in 23 African population groups, encompassing the Caucasoid, Negroid, Khoisan and Pygmy populations. The frequency of the polymorphism was higher than previously reported, with the rarer allele occurring at frequencies ranging up to 0.41. No distinct trends in population frequency were observed, suggesting that the polymorphism is of little value in anthropological population studies. The existence of several TaqI mutations, in both time and position within the repeat unit, is indicated. PMID- 8514324 TI - Alpha-2-HS-glycoprotein gene frequencies in Galicia: further evidence for a cline in European populations. AB - alpha 2-HS-glycoprotein (AHSG) phenotypes were determined in 506 unrelated autochthonous individuals from the Galician population (NW Spain) by means of isoelectric focusing followed by silver stain immunofixation. The phenotype frequency distribution fitted with the Hardy-Weinberg law. No evidence of intrapopulation heterogeneity was observed. The allele frequencies obtained were: AHSG*1 = 0.7559 +/- 0.013 and AHSG*2 = 0.2441 +/- 0.013. Our findings lend support to the hypothesis of an AHSG gene frequency cline in European populations. Other population genetics' considerations have also been discussed. PMID- 8514325 TI - TaqI polymorphism of the epidermal growth factor receptor gene in Caucasoids and Japanese. AB - Genetic polymorphism of the epidermal growth factor (EGF) receptor gene following Taq I digestion was compared between samples of genomic DNA from glioma-derived cell lines and Caucasoid and Japanese subjects. The same three allelic forms of the EGF receptor gene, marked by variant fragments of approximately 12.8, 11.6 and 10.8 kb in size were common to both ethnic groups and the 12.8- and 11.6-kb fragments were found in the glioma-derived cell line DNA. A further variant fragment of approximately 13.8 kb in size has been shown to be thus far restricted to the Japanese. These data suggest that most allelic forms of the EGF receptor gene recognized by Taq I restriction fragment length polymorphism have a long evolutionary history and probably do not predispose to development of malignant glioma. PMID- 8514326 TI - Similarity of DNA fingerprints due to chance and relatedness. AB - Given the DNA fingerprints of two individuals with some bands being shared by both individuals, we define a new measure of the degree of similarity between the DNA profiles of two individuals. We use this measure to calculate the expected DNA similarity of two unrelated individuals of a randomly mating population; this similarity is due to chance only. Then, the expected similarity between two related individuals is obtained; this similarity is due to chance and relatedness. From these results, the degree of similarity due to relatedness alone may be calculated. PMID- 8514327 TI - Transferrin subtypes in some Eurasian and African populations. AB - Transferrin (TF) subtypes in blood serum were assessed by isoelectric focusing in 2,035 healthy unrelated individuals from populations in different regions of Eurasia and Africa. Considerable heterogeneity for TF subtypes was found between the populations studied. The data obtained were compared with those of other investigators. PMID- 8514329 TI - Does the transferrin C2 frequency depend on age? AB - In a previous study Beckman and Beckman [Hum Hered 1986;36:254-255] reported a decrease in the Tf C2 frequency with age, from 0.173 in newborns to 0.099 in 70 year-old healthy individuals. The authors suggested a selective disadvantage for Tf C2. In a population from Leipzig (FRG) older people have the highest C2 gene frequency (0.1701 vs. 0.1629 in children < 5 years). The differences are not significant. A dependency of C2 frequency on age seems to remain in question. PMID- 8514328 TI - Linkage analysis of schizophrenia: the D1 dopamine receptor gene and several flanking DNA markers. AB - Alterations in dopaminergic activity may play an important role in the pathogenesis of schizophrenia. The central effects of dopamine are mediated by at least five G protein-coupled receptors, D1, D2, D3, D4 and D5. The D1 receptor maps to 5q35.1 and it identifies an Eco RI as well as a Taq I RFLP. In the present study we undertook a linkage analysis between the D1 receptor RFLPs and schizophrenia in 9 multigenerational families in which segregation of disease was consistent with autosomal dominant inheritance and reduced penetrance. Several flanking DNA markers were also analyzed as the D1 receptor RFLPs were relatively uninformative in our families. Pairwise analyses of schizophrenia and several flanking markers indicate that inheritability of this region is unlikely to be involved in the pathogenesis of schizophrenia in the 9 families studied. PMID- 8514330 TI - Serum protein markers (Hp, GC, C3) in patients with colon cancer. AB - The phenotypes and gene frequencies of three serum protein systems--Hp, GC and C3 -were studied in 184 consecutive patients from all over Greece with colon cancer. Healthy Greeks studied previously in our department served as controls. No significant differences were found between patients and controls concerning GC and C3. Significant differences were found in the Hp system; the frequencies of the Hp*1 gene and the Hp 1-1 phenotype were significantly higher in patients than in controls. PMID- 8514331 TI - Gangliosides protect from TNF alpha-induced apoptosis. AB - The modulation of tumor necrosis factor alpha-mediated cytotoxicity by gangliosides was analyzed. When cells of the TNF alpha-sensitive fibrosarcoma cell line L929 were incubated for 16 h with recombinant TNF alpha (156 or 312 pg/ml), they were lysed to 65.2% or 78.0%, respectively. The presence of a bovine brain ganglioside mixture (BBG, Cronassial) inhibited the TNF alpha-mediated lysis in a dose-dependent manner (IC50 approximately 1 mg/ml). Maximum inhibition was achieved with 2 mg/ml BBG (82.6% inhibition for 156 pg/ml TNF alpha and 88.5% inhibition for 312 pg/ml TNF alpha). In situ nick translation revealed that BBG (2 mg/ml) significantly reduces the number of cells with TNF alpha-induced DNA strand breaks from 71.2% to 6.6% (P < 0.0001), indicating a protection against TNF alpha-mediated apoptosis. We conclude that BBG prevents the cytotoxic action of TNF alpha on tumor cells. The inhibitory effect may be due to an interference of gangliosides with intracellular signal transduction pathways, resulting in an inhibition of the activation of DNA-cleaving endonucleases. PMID- 8514332 TI - Red-cell bound anti-A is more efficient than anti-B in competition for fluid phase complement. AB - Lysis of group A and B erythrocytes by human complement was studied by an anti-A (BRIC.131) and an anti-B (BRIC.30) IgM monoclonal antibody in a 51Cr-release assay. The relative concentration of membrane-bound immunoglobulins was detected by flow cytometric analysis, and the amount of C1q and C3 bound to the sensitized red cells was measured by using purified, 125I-labelled molecules. The direct haemolysis was identical with both reagents in the presence of excess and suboptimal complement over a wide range of antibody concentration (between 50 and 7000 ng/ml). The indirect effect of membrane-bound antibody, i.e. its influence on complement binding by sensitized bystander cells, was examined in a cold target competition assay in which sensitized, non-labelled cells are present when complement is incubated with sensitized labelled cells. We have found that the competitive capacity of sensitized erythrocytes correlated with the amount of membrane-bound immunoglobulins. In accordance with our earlier findings, an equal level of target and competitor cell lysis was obtained only if the fluid phase anti-B antibody concentration was 2 to 4 times higher than that of the anti-A antibodies. We demonstrate in this paper that the different competitive activity of IgM anti-A and anti-B monoclonal antibodies might be accounted for by differences in their C1q and C3 binding capacities. PMID- 8514333 TI - Interactions in the complement-mediated lysis of blood group AB erythrocytes sensitized simultaneously with anti-A and anti-B monoclonal antibodies. AB - The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization. PMID- 8514334 TI - A prominent natural H-2 Kd ligand is derived from protein tyrosine kinase JAK1. AB - The first natural MHC ligand to be sequenced directly was the nonapeptide SYFPEITHI eluted from H-2 Kd molecules of a mouse tumour line, P815 [1]. A GenBank search indicated high homology to a nonapeptide contained within the human tyrosine kinase JAK1: SFFPEITHI, residues 355-363 [2]. This high homology prompted us to look at whether the mouse JAK1 protein has a Tyr residue at position 356 instead of Phe as in the human sequence. Cloning and sequencing of the mouse homologue gene confirmed that this is indeed the case. Thus, the physiological MHC ligand SYFPEITHI is derived from the protein tyrosine kinase, JAK1. The mouse tumor line P815 expresses the 5.4-kb JAK1 mRNA, and the 130,000 kDa JAK1 protein can be readily detected. PMID- 8514335 TI - Multiple forms of the G protein-related beta subunit in Daudi lymphoblastoid cells. AB - We have explored the forms of the G protein-related beta subunit which are present in Daudi lymphoblastoid cells. Northern blotting with labeled beta-1 and beta-2 probes indicates that two messages of 3.3 kb and 1.7 kb are present for both beta-1 and beta-2, implying that multiple forms of the beta subunit are present. Antibodies were raised against two peptides of the beta subunit (residues 1-23 and 127-145). Both antibodies detected subunits at 35 kDa and 31 kDa, of which the 35-kDa form predominates in the membrane fraction and the 31 kDa one in the cell cytosol. Crosslinking of the membrane fraction with the cleavable crosslinker (DTSSP) caused a simultaneous diminution in the 31-kDa form while increasing the amount of the 35-kDa form--a pattern which was reversed upon the reduction of these crosslinks with DTT. Studies of the soluble form indicate that this is truly a soluble protein since centrifugation at 200,000 x g for 2 h did not diminish the levels of the protein in the soluble fraction. Sedimentation analysis indicates that the soluble beta-homologue is found in fractions which overlap with those which contain the mu chain of immunoglobulin at a position clearly distinct from the expected positions of free mu or free beta. Our results suggest that at least two forms of a subunit which is closely related to, or identical with, the beta subunit of G proteins are present in Daudi cells. PMID- 8514336 TI - Phorbol ester-induced effects on cell cycle progression and terminal deoxynucleotidyltransferase (TdT) activity in KM-3 pre-B cell line. AB - Phorbol myristic acetate (PMA) is a tumor-promoting agent that has been shown to induce differentiation of human leukemia cells and of normal lymphoid cells. We have investigated the ability of PMA to induce inhibition of cell growth of the human KM-3 pre-B leukemic cell line by multiparametric analysis. Our results show that PMA treatment induces cell differentiation with the disappearance of terminal deoxynucleotidyltransferase and a decrease of cell growth, as evaluated by [3H]thymidine uptake. Flow cytometric analysis of BrdU incorporation shows that PMA is able to induce a modification of the cell cycle with a sharp decrease of the percentage of S-phase cells, which is more evident after 24 h of treatment. Comparison between the cell growth kinetics and TdT synthesis and activity shows that differentiated cells are still able to proliferate to a certain extent and that the TdT disappearance and the initial decrease of cell proliferation are two independent effects of PMA. PMID- 8514337 TI - Immunomodulatory action of human recombinant erythropoietin in man. AB - Recent findings suggest that recombinant human erythropoietin (rhEpo) may have an immunomodulating action. We have studied the in vitro and in vivo effects of rhEpo on immune functions in man. Low pharmacological concentrations of the hormone inhibit T-cell activation and proliferation, while higher ones are without that effect. The same Epo concentrations inhibit mitogen- and alloantigen driven B-cell differentiation and immunoglobulin synthesis and, to a lesser extent, B-cell proliferation. In vivo treatment with rhEpo causes an initial inhibition of T- and B-cell proliferation, but with prolonged administration improved responsiveness is observed. Our data support the notion that rhEpo can regulate immune functions, a fact of potential clinical application. PMID- 8514338 TI - Natural antibodies to avidin in human serum. AB - Human serum was found to contain natural antibodies to the egg-white glycoprotein avidin. Of 270 samples tested, all contained antibodies to different extents, mainly of the IgG and IgM classes. Anti-avidin antibodies could be isolated by affinity chromatography. PMID- 8514339 TI - Protein A used in DELFIA for the determination of specific antibodies. AB - The conditions of protein A labelling with Eu chelates were studied. The conjugates obtained were compared with those from horseradish peroxidase used conventionally in immunochemical practice. Protein A-Eu conjugates were obtained by a method applied previously for antibody labelling with indium and europium chelates using the bicyclic dianhydride of diethylenetriaminepenta-acetic acid (DADTPA) with some modifications. The Eu-labeled protein A ensured a sensitivity of the IgG determination at the level of 2 ng/ml and a dynamic range of the determination from 3 to 1000 ng/ml, which significantly exceed analogous values for the protein A-peroxidase conjugates. The Eu-labeled protein A was used for the determination of antibodies to Francisella tularensis in the sera of humans vaccinated against tularemia. The assay values exceeded by 10-40-fold the results of an ELISA in sensitivity. It was deduced that the Eu-labeled protein A can be effectively used for the determination of antibodies specific to a tularemia causative agent. In particular, this compound can be useful for the determination of specific antibodies in low immune sera. PMID- 8514340 TI - Dietary management of lactose intolerance--lactase treated milk versus soya milk. AB - Transient lactose intolerance secondary to infective diarrhoea is common in developing countries, & soya milk formula is commonly prescribed for its management. Lactose predigested milk feeding was done in 70 patients of test group while withdrawing lactose diet & 84.3% had control of motions with absent lactose in stool despite challenge feed, 3 days after withdrawal of lactose diet. 83.3% patients in control group fed soya milk had such improvement but the incidence of feed refusal was 30% in this group as compared to only 2.8% in lactaid group. Vomiting after feed was also found in 10% of babies fed soya milk as compared to none in lactaid group, thus proving superiority of lactaid in management of lactose intolerance diarrhoea. PMID- 8514341 TI - Mortality profile in trauma victims. AB - To assess the mortality incidence among trauma victims, one year prospective study comprising all patients admitted in Rajendra Hospital, Patiala, Punjab with physical trauma was undertaken. Road traffic accidents were the commonest cause of trauma-death followed closely by thermal injury. Mortality was highest among victims of multiple injuries. The mortality rate increased in direct proportion to increase in transportation time and Injury Severity Score (ISS). We advocate some simple preventive and regulatory steps to lower the mortality incidence in trauma cases. PMID- 8514342 TI - Teenage pregnancy and its effect on maternal and child health--a hospital experience. AB - Sixteen mothers died out of 2279 teenage deliveries contributing a high maternal mortality rate of 7.02 per 1000 during the study period. 15 adolescent mothers who died had no access to prenatal care. An increased incidence of low birth weight (less than 2.5 kg) babies was observed among teenage deliveries. Incidence of premature deliveries were more among teenage mothers. Severe anemia, puerperal sepsis and hypertension were the dominant complications experienced among adolescent mothers. PMID- 8514343 TI - Methods of analysis for environmental carcinogens. PMID- 8514344 TI - Exposure assessment from field studies. PMID- 8514345 TI - Integrated lifetime exposure. PMID- 8514346 TI - Determination of radon using activated charcoal. PMID- 8514347 TI - Sources of pollutants in indoor air. AB - In order to ensure an impeccable indoor air quality, it is important to do so, whenever possible, by means of source-control. In particular, this general principle should be applied with regard to contamination originating from building materials and furnishings. For such materials, quality requirements should be established to keep the concentration of emitted pollutants below admissible limits. In the case of building materials, a general declaration of all constituents should be mandatory and carcinogenic compounds like asbestos and benzene should be prohibited for use in indoor environments. If the emission of a specific pollutant cannot be avoided, its concentration in indoor air can be kept below the tolerated limit by increasing the ventilation. Increased concentrations of nitrogen dioxide due to the use of combustion appliances in kitchens and bathrooms can be avoided by exhausts. In geographical areas with high radon emission, however, corrective measures have to be evaluated individually. To eliminate the contaminants originating from human activities (e.g., carbon dioxide, body odours), adequate ventilation is required and depends on the occupancy and the use of the room; to maintain an acceptable air quality, the carbon dioxide concentration should not exceed 0.1-0.15%. Increased ventilation also reduces acute irritations if smoking is allowed. Here, the required air supply is dependent on the degree of annoyance which is considered to be acceptable to the user of the room. Acceptable indoor air quality can largely be maintained today because of the extensive knowledge and experience now accumulated in this field. However, the complex relationships between air quality and human health require further study. More research in the field of building materials is particularly desirable. PMID- 8514348 TI - Determination of asbestos in lung tissue using transmission electron microscopy. PMID- 8514349 TI - Determination of airborne organic compounds using Tenax GC and gas chromatography mass spectrometry. PMID- 8514350 TI - Determination of organic solvent vapours in indoor air using charcoal adsorption and gas chromatography. PMID- 8514351 TI - Determination of the long-term averaged concentration of volatile aromatic hydrocarbons in indoor air by charcoal adsorption, solvent extraction and gas chromatography. PMID- 8514352 TI - Breath sampling. PMID- 8514353 TI - Near-real-time determination of formaldehyde in air using a CEA Instruments Inc. Model 555 Analyzer. PMID- 8514354 TI - Determination of formaldehyde in indoor air by a liquid sorbent technique. PMID- 8514355 TI - Determination of formaldehyde in indoor air by a solid sorbent technique. PMID- 8514356 TI - Determination of nitrogen dioxide by means of the Palmes diffusion tube and the Yanagisawa filter badge. PMID- 8514357 TI - Determination of airborne nitrosamines by means of air-sampling cartridges and GC TEA. PMID- 8514358 TI - Determination of nicotine and minor tobacco alkaloids in indoor air by absorption and gas chromatography. PMID- 8514359 TI - Determination of haemoglobin adducts of aromatic amines by gas chromatography mass spectrometry. PMID- 8514360 TI - Radioimmunoassay for nicotine and cotinine. PMID- 8514361 TI - Analysis of mutagens by the microsuspension mutagenicity assay in Salmonella typhimurium. PMID- 8514362 TI - Analysis of mutagens by the microsuspension forward-mutation assay in Salmonella typhimurium strain TM677. PMID- 8514363 TI - Cooking, heating and air treatment pollutants in indoor environments. PMID- 8514364 TI - Determination of extractable particulate organic matter and selected polycyclic aromatic hydrocarbons. PMID- 8514365 TI - Determination of metals on airborne particulates by atomic absorption spectrometry. PMID- 8514366 TI - Determination of carbon monoxide in indoor air with a direct-reading instrument. PMID- 8514367 TI - Determination of the time-weighted average concentration of carbon monoxide in air using a long-term detector tube. PMID- 8514368 TI - Determination of pesticides and polychlorinated biphenyls in indoor air by gas chromatography. PMID- 8514369 TI - Indoor air exchange and ventilation rate. PMID- 8514370 TI - Indoor concentrations of environmental carcinogens. PMID- 8514371 TI - Effects of indoor air pollution on human health. PMID- 8514372 TI - Indoor air controls. PMID- 8514373 TI - Bioassay of complex mixtures of indoor air pollutants. AB - The development of short-term genetic bioassays has made it possible to conduct mutagenicity studies on complex mixtures of indoor air pollutants. Although most of the studies have used the standard S. typhimurium/microsome reversion assay developed by Ames et al. (1975), the development of microsuspension mutagenesis methods (see Methods 18 and 19, this volume) has facilitated wider use of bioassays in indoor air pollution studies. It is clear from the studies reviewed here that environmental tobacco smoke is the major source of mutagens indoors. Other sources which produce significant, but much smaller, increases in indoor air mutagenicity include outdoor air and other indoor combustion sources (e.g., cooking, kerosene heaters and open fireplaces burning wood). These studies have been based on measurement of the bacterial mutagenicity of extracts from particulate matter. A limited number of reports, however, indicate that volatile and semi-volatile constituents of indoor air may also be mutagenic and deserve further study. PMID- 8514374 TI - Sampling strategies for indoor air analyses. COST 613 document. PMID- 8514375 TI - Choice of bacteria in animal models of sepsis. PMID- 8514376 TI - Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection. AB - Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis. PMID- 8514377 TI - Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers. AB - The mechanisms whereby enteropathogenic Escherichia coli (EPEC) causes diarrhea remain undefined. We found that EPEC caused a decrease in transepithelial electrical resistance across polarized monolayers of Caco-2 and MDCK epithelial cells. This occurred approximately 6 to 10 h after bacterial addition and was reversible if the monolayers were treated with tetracycline or gentamicin. Although significant alterations in host actin occurred beneath adherent EPEC, actin filaments supporting tight junctions were not noticeably affected in the epithelial cells, nor was the distribution of ZO-1, a tight junction protein. Despite the decrease in transepithelial electrical resistance, EPEC did not cause an increase in [3H]inulin penetration across MDCK monolayers. Unlike in the parental strain, mutations in any loci involved in adherence or formation of attaching and effacing lesions were unable to cause a decrease in transepithelial resistance. These data indicate that EPEC causes a decrease in transepithelial electrical resistance by disrupting a transcellular (intracellular) pathway rather than by disrupting intercellular tight junctions (paracellular) and that these disruptions occur only when attaching and effacing lesions are formed. PMID- 8514378 TI - Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages. AB - Central to understanding the pathogenesis of tuberculosis is the interaction between the pathogen and mononuclear phagocytes. A key question about that interaction is whether Mycobacterium tuberculosis exerts an effect on phagolysosome fusion. We have reexamined the dynamics of phagolysosome fusion and its effect on intracellular bacterial replication in M. tuberculosis-infected macrophages by performing an extensive study at the electron microscopic level. Thoria-labelled murine and human macrophages were infected with a virulent (H37Rv) or avirulent (H37Ra) strain of M. tuberculosis or with Mycobacterium bovis BCG vaccine for times ranging from 2 h to 7 days. In all cases, by 2 h postinfection, approximately 85% of the bacteria clearly resided in fused vacuoles. However, at 4 days postinfection, fusion levels for viable H37Rv and H37Ra were reduced by half, whereas the fusion profiles of BCG and of heat-killed H37Rv and H37Ra were unchanged. A comparison of the numbers of bacteria per fused and nonfused vacuoles suggests both a net transfer of bacteria out of fused vacuoles and preferential bacterial multiplication in nonfused vacuoles. H37Rv and H37Ra appeared to bud from the phagolysosomes into tightly apposed membrane vesicles that did not fuse with secondary lysosomes. In some cases, no such membrane was seen and the bacteria appeared to be free in the cytoplasm. Only viable H37Rv showed a significant increase in bacterial counts during the course of infection. Thus, both of the attenuated strains we examined differed from the virulent strain H37Rv in their abilities to replicate successfully within macrophages, but each diverged from H37Rv at a different point in the process. Viable tubercle bacilli H37Rv and H37Ra had the capacity to escape from fused vesicles as the infection progressed; BCG did not. After extrusion from the phagolysosome, H37Rv, but not H37Ra, was able to multiply. These results suggest a novel mechanism by which virulent M. tuberculosis eludes the microbicidal mechanisms of macrophages by escaping from fused phagolysosomes into nonfused vesicles or the cytoplasm. PMID- 8514379 TI - Identification of a carbohydrate recognition domain in filamentous hemagglutinin from Bordetella pertussis. AB - The adherence of Bordetella pertussis to ciliated cells and macrophages is critical to colonization and infection of the respiratory tract. Adherence to both types of cells involves the recognition of eukaryotic carbohydrates by the bacterial adhesin filamentous hemagglutinin (Fha). The carbohydrate recognition domain (CRD) of Fha is considered an important antigen for subcomponent vaccines to maximize the generation of antiadherence antibodies capable of protecting against colonization. For identification of the CRD of Fha, a bank of eight monoclonal antibodies (MAbs) that mapped to four contiguous regions were tested for their ability to block Fha binding to lactosylceramide or to block bacterial binding to ciliated cells. Only MAb 12.5A9, which maps to amino acid residues 1141 to 1279, blocked both Fha binding to lactosylceramide and bacterial binding to ciliated cells. An 18-kDa polypeptide corresponding to this region was expressed in Escherichia coli. Cell lysates containing this protein bound to lactosylceramide in a manner identical to that of native Fha. Mutant strains of B. pertussis that contained an in-frame deletion of the coding sequence for this region produced a truncated Fha that showed negligible cross-reactivity with MAb 12.5A9. In an adherence assay, these mutant strains failed to bind efficiently to either ciliated cells or macrophages. The numbers of adherent bacteria for these strains were reduced to the number obtained with a nonadherent strain. We conclude that the region defined by residues 1141 to 1279 of Fha constitutes a CRD critical for bacterial adherence and represents a potential candidate for a subcomponent vaccine. PMID- 8514380 TI - An anti-CD3 monoclonal antibody protects mice against a lethal infection with Listeria monocytogenes through induction of endogenous cytokines. AB - Mice were protected against a lethal infection with Listeria monocytogenes when treated with low doses of an anti-CD3 monoclonal antibody (MAb). Injection of anti-CD3 MAb induced rapid production of endogenous tumor necrosis factor (TNF) in the spleens and endogenous gamma interferon (IFN-gamma) in the bloodstreams and spleens of mice. Administration of anti-Thy1.2 MAb or a combination of anti CD4 MAb and anti-CD8 MAb resulted in suppression of anti-CD3 MAb-induced endogenous cytokine production and antilisterial resistance. Alternatively, in vivo depletion of anti-CD3 MAb-induced TNF and IFN-gamma by the simultaneous administration of antibodies against TNF and IFN-gamma suppressed anti-CD3 MAb induced antilisterial resistance. Moreover, injection of anti-complement receptor type 3 (Mac-1, CD11b) resulted in inhibition of anti-CD3 MAb-induced antilisterial resistance. These results suggest that the preventive effect of anti-CD3 MAb might be due to activation of phagocytes by TNF and IFN-gamma induced by stimulating CD4+ T cells and CD8+ T cells with the MAb. Furthermore, treatment with anti-CD3 MAb did not inhibit establishment of acquired resistance against secondary infection with L. monocytogenes. PMID- 8514381 TI - Localization of the ActA polypeptide of Listeria monocytogenes in infected tissue culture cell lines: ActA is not associated with actin "comets". AB - The ActA protein of the gram-positive pathogen Listeria monocytogenes is a 90-kDa polypeptide required for interaction of the bacteria with components of the host cell microfilament system to generate intra- and intercellular movement. To study the localization, distribution, and expression of the ActA polypeptide in L. monocytogenes grown either in broth culture or in infected tissue culture cells, we first isolated ActA by monoclonal antibody-based immunoaffinity chromatography. Polyclonal rabbit antisera raised against purified ActA revealed that ActA was associated with the cell wall and exposed on the surface of the bacteria, readily accessible to ActA antibodies. In contrast, a C-terminally truncated ActA1 polypeptide expressed by the isogenic actA1 mutant was detected only in the supernatant fluids. Immunofluorescence microscopy and electron microscopic studies using immunogold labeling showed that ActA was present on the surface of the bacteria infecting PtK2 and J774 cells at all stages of the infection cycle and was not found to be associated with the actin "tail" of individual bacteria. For the isogenic actA1 mutant strain, which grew as microcolonies within infected cells, only diffuse staining of the secreted ActA1 polypeptide in the host cytoplasm was observed. The ActA polypeptide therefore appears to be required in the initiation of actin accumulation by the bacterium and is apparently not directly involved in the generation of the actin tail. Analysis of strains of several L. monocytogenes serotypes indicated microheterogeneity in the molecular weights of the ActA polypeptides of individual strains and led to the detection of a serotype 3a strain that does not produce ActA. PMID- 8514382 TI - Hypoexpression of major histocompatibility complex molecules on Legionella pneumophila phagosomes and phagolysosomes. AB - Legionella pneumophila is a facultative intracellular pathogen that parasitizes host mononuclear phagocytes. Cell-mediated immunity is pivotal to host defense against L. pneumophila, and the infected host cell may play a central role in processing and presenting parasite antigens to lymphocytes mediating cell mediated immune response. However, in the case of L. pneumophila and intracellular parasites in general, little is known about the intracellular trafficking of parasite antigens, the influence of parasite infection on major histocompatibility complex (MHC) expression, or the relationship of MHC molecules to sites of parasite replication. To learn more about this, we have used flow cytometry to study the expression of HLA-DR by monocytes infected with L. pneumophila and cryosection immunogold electron microscopy to study the distribution of MHC class I and II molecules on L. pneumophila phagosomes. Flow cytometry analysis demonstrated that L. pneumophila infection has little effect on the overall expression of HLA-DR by monocytes. Cryosection immunogold studies revealed abundant staining for MHC class I and II molecules on the plasma membrane of infected monocytes but little or no staining on the membranes of mature L. pneumophila phagosomes. Cryosection immunogold studies of an avirulent mutant of L. pneumophila that, unlike the wild type, does not inhibit phagosome lysosome fusion and subsequently survives but does not multiply in a phagolysosome yielded similar results. We have previously found that MHC class I and II molecules are excluded from nascent phagosomes during coiling and conventional phagocytosis. The present work demonstrates that MHC molecules do not accumulate appreciably in the L. pneumophila phagosome as it matures and at a point in the life cycle of the organism in which it is replicating and producing immunoprotective T-cell antigens. This suggests that L. pneumophila does not reside in a typical endosomal compartment in the host cell and that L. pneumophila antigens may encounter MHC molecules at extraphagosomal sites within the host cell. PMID- 8514383 TI - Cloning and sequencing of the gene encoding a 31-kilodalton antigen of Haemophilus somnus. AB - Immunoblots using bovine antibody against Haemophilus somnus as the primary antibody consistently identified 31-, 40- and 78-kDa proteins in Sarkosyl insoluble extracts of H. somnus. A genomic library of H. somnus 8025 DNA was constructed in plasmid pUC19, and 45 recombinants expressed proteins which were recognized by bovine antiserum in Western blots (immunoblots). Ten of the recombinants expressing a 31-kDa protein caused the lysis of bovine erythrocytes. Restriction endonuclease mapping indicated that the hemolytic recombinants shared an approximately 1.7-kb BglII fragment. Southern blot analysis using the BglII fragment as a probe revealed homology among the recombinants and the presence of an identically sized BglII fragment in the chromosome of all H. somnus isolates tested. Sequence analysis indicated the presence of an 822-bp open reading frame within the 1.7-kb BglII fragment. Deletion of this open reading frame resulted in the loss of hemolytic activity and protein expression in recombinant Escherichia coli, suggesting the possible role of the 31-kDa protein as a hemolysin. An amino acid sequence deduced from the DNA sequence shared homology with outer membrane protein A of E. coli, Salmonella typhimurium, and Shigella dysenteriae, with P6 of Haemophilus influenzae, and with PIII of Neisseria gonorrhoeae. An amino acid analysis of the recombinant 31-kDa protein agreed with the amino acid composition deduced from the DNA sequence. PMID- 8514384 TI - Mapping of immunoreactive sites of pneumococcal pneumolysin by use of synthetic peptides. AB - In the search for better diagnostic tools and improved vaccines against pneumococcal diseases, continuous antigenic sites of the pneumococcal pneumolysin molecule were identified with partially overlapping synthetic peptides. Peptides were derived from the predicted amino acid sequence according to the known DNA sequence of pneumolysin. The immunoreactivities of the peptides were studied by enzyme immunoassay with seven human serum samples and three rabbit hyperimmune serum samples. Two immunoreactive sites in the overlapping peptides at the amino terminal end of the pneumolysin molecule were identified in this study. Two common immunoreactive sites for both human and rabbit sera were demonstrated. PMID- 8514385 TI - Primary structure of and immunoglobulin E response to the repeat subunit of gp15/400 from human lymphatic filarial parasites. AB - We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti. The amino acid sequence of the 15-kDa subunit, derived from the nucleotide sequence of the gene fragment from B. malayi, is identical to that previously reported for B. pahangi, whereas the derived W. bancrofti protein sequence differs in only 7 of 132 residues. The identity of the protein in the two Brugia species allowed us to use a recombinant from B. pahangi to examine the serological response of adult Indonesian subjects infected with B. malayi. The polymerase chain reaction-amplified subunit was expressed in Escherichia coli via the pDS56/RBS11 plasmid and purified by nickel-chelating chromatography. A significant proportion of individuals produced antigen-specific immunoglobulin E (IgE). This was most pronounced in the individuals with elephantiasis, with 14 of 15 showing elevated titers and a mean of 3.2 ng of specific IgE ml-1. Only 2 of 15 microfilaremic individuals possessed elevated titers of specific IgE, with a mean of 0.045 ng ml-1 for the group as a whole. Asymptomatic amicrofilaremic residents showed approximately equal numbers of responders (defined as having a value in the radioimmunoassay greater than two standard deviations above controls) and nonresponders, with a group mean of 1.2 ng of antigen-specific IgE ml-1. PMID- 8514386 TI - Enhancement of interleukin-4 production by pertussis toxin. AB - Pertussis toxin (PT), a protein toxin of Bordetella pertussis, has many biological activities, including potent adjuvant capacity and the ability to up regulate immunoglobulin E (IgE) production. Interleukin-4 (IL-4) is a cytokine which is essential for the IgE response. Accordingly, we examined the effect of PT on IL-4 production. Spleen and lymph node cell suspensions were prepared from immunized mice and cultured with antigen or polyclonal stimuli in vitro. IL-4 secretion was assessed by bioassay, and IL-4 mRNA expression was assessed by reverse transcription and polymerase chain reaction. Significantly larger amounts of IL-4 protein and mRNA were produced in vitro by cells from mice given PT at the time of immunization than by cells from mice given antigen alone, PT alone, or the combination of antigen with cyclophosphamide. Total and antigen-specific serum IgE levels were significantly elevated in immunized mice given PT, compared with the other groups. Thus, there was a relationship between serum IgE and IL-4 production. The administration of a single dose of an anti-IL-4 monoclonal antibody in vivo, at the time of immunization and treatment with PT, abolished the development of the IgE response. These results indicate that PT is a potent stimulus for the production of IL-4, which is required for the adjuvant effect of PT on IgE formation. PMID- 8514387 TI - Cytokine response of T-cell subsets from Brucella abortus-infected mice to soluble Brucella proteins. AB - Hot saline extracts of Brucella abortus 19 were separated by successive differential precipitation with 50 and 70% ammonium sulfate, yielding fractions SBP50, with predominantly 36-kDa proteins and a number of medium-sized proteins (26 to 33 kDa), and SBP70, with 14-kDa and lower-molecular-mass proteins. Both fractions stimulated specifically proliferation and cytokine production by spleen cells from brucella-infected mice, although the activity of SBP50 was much higher than that of SBP70. Further separation of SBP50 by a DEAE-Sepharose column resulted in three distinct subfractions which were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The three subfractions were analyzed for their abilities to induce lymphocytes to proliferate and produce cytokines. The three subfractions were all active but with characteristic differences in magnitude. Subfraction 1 stimulated moderate proliferation, high interleukin 6 (IL-6) production, and relatively low production of gamma interferon (IFN-gamma). Subfraction 2 was the strongest stimulus for proliferation and production of IL-6 and IFN-gamma, while subfraction 3 stimulated moderate cell proliferation, a high level of IFN-gamma, and a low level of IL-6. IL-2 production stimulated by the three subfractions was similar. SBP50 and all three subfractions stimulated purified T cells of both CD4+ and CD8+ subsets to produce IFN-gamma. The production of IFN-gamma by CD8+ T cells to brucella antigens was enhanced with exogenous IL-2. PMID- 8514388 TI - Characterization of cellular infiltrates and cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response. AB - Cryptococcosis, an increasingly important opportunistic infection caused by the encapsulated yeast-like organism Cryptococcus neoformans, is limited by an anticryptococcal cell-mediated immune (CMI) response. Gaining a thorough understanding of the complex anticryptococcal CMI response is essential for developing means of controlling infections with C. neoformans. The murine cryptococcosis model utilizing footpad swelling to cryptococcal antigen (delayed type hypersensitivity [DTH]) has proven to be a valuable tool for studying the induction and regulation of the anticryptococcal CMI response, but this technique has limitations with regard to evaluating the role of the final effector cells recruited by an ongoing CMI response. The purpose of this study was to assess the types of cells and cytokines induced into the site of cryptococcal antigen deposition in C. neoformans-infected and -immunized mice compared with those for control mice. We used a gelatin sponge implant model to examine the cells and cytokines present at the site of an anticryptococcal DTH response. Sponges implanted in infected mice and injected with cryptococcal culture filtrate antigen (CneF) 24 h before assessment had significantly increased numbers of infiltrating leukocytes compared with saline-injected sponges in the same animals. Exaggerated influxes of neutrophils and mononuclear cells were the major contributors to the increase in total numbers of cells in the DTH-reactive sponges. The numbers of CD4+ and LFA-1+ cells were found to be significantly increased in the CneF-injected sponges of infected and immunized mice over the numbers in control sponges. The numbers of large granular lymphocytes were also increased in DTH-reactive sponges compared with control sponges. Gamma interferon, interleukin 2 (IL-2), and IL-5 are clearly relevant cytokines in the anticryptococcal CMI response, since they were produced in greater amounts in the CneF-injected sponges from C. neoformans-infected and -immunized mice than in control sponges. IL-4 was not associated with the expression of DTH to cryptococcal antigen. The gelatin sponge model is an excellent tool for studying cells and cytokines involved in specific CMI responses. PMID- 8514389 TI - Capsular polysaccharide regulates neutrophil complement receptor interactions with type III group B streptococci. AB - The capsular polysaccharide of type III group B streptococci contributes substantially to the virulence of this organism. We explored the extent to which capsular polysaccharide influences neutrophil complement receptor interactions by using a poorly encapsulated strain (COH 31r/s), two well-encapsulated strains (M732 and M912), and strains produced from COH 31r/s by transposon mutagenesis that lacked capsule (COH 31-15) or had capsular polysaccharide lacking terminal sialic acid residues (COH 31-21). When tested with normal human serum, each strain had initially high bactericidal indices (85 to 96%). Monoclonal antibody blockade of neutrophil complement receptor 3 (CD11b/CD18) inhibited opsonophagocytosis to a significantly greater extent for the well-encapsulated strain than for the poorly encapsulated, asialo, or unencapsulated mutant strain. The addition of antibody with specificity for capsular polysaccharide reduced the inhibitory effect significantly for the encapsulated but not for the mutant strains. Blockade of neutrophil complement receptor 1 (CD35) effected only low level inhibition. However, simultaneous blockade of complement receptors 1 and 3 augmented the inhibitory effect. When hypogammaglobulinemic serum was used as an antibody-free complement source, the initial bactericidal index was low (30% +/- 15%) for an encapsulated strain and was not affected for the mutant strains. Blockade of either neutrophil complement receptor 1 or 3 or the combination fully inhibited killing of the encapsulated strain. These results demonstrate that the type III group B streptococcal capsular polysaccharide regulates interactions with neutrophil complement receptors. We conclude that efficient phagocytic killing of encapsulated group streptococci in nonimmune serum requires ligation of complement receptors 1 and 3. PMID- 8514390 TI - Endogenous gamma interferon is essential in granuloma formation induced by glycolipid-containing mycolic acid in mice. AB - The present study examined the role of endogenous gamma interferon (IFN-gamma) in the formation of granulomas in mice which had been given a single intravenous injection of glycolipid-containing mycolic acid (trehalose 2,3,6'-trimycolate) purified from cell walls of Rhodococcus aurantiacus (Gordona aurantiaca) (GaGM) in the form of liposome. The histological status of granuloma formation in the livers, spleens, and lungs of GaGM-injected mice was studied at weeks 1 through 5, and the titers of endogenous IFN-gamma in all of these organ extracts and in the sera were determined by enzyme-linked immunosorbent assay. The granulomas, composed of epithelioid cells, developed until 3 weeks postinjection, and thereafter the granulomas regressed. The production of endogenous IFN-gamma was biphasic, with an early phase detected at days 1 through 3 and a late phase detected at weeks 1 through 5. The latter peak of endogenous IFN-gamma production proceeded in parallel with granuloma formation. Both the areas of granulomas and titers of IFN-gamma in these organs were dependent on the doses of GaGM used for injection. The cells which produce endogenous IFN-gamma in the spleens appear within the granulomas. To study the role of endogenous IFN-gamma in granuloma formation, the in vivo administration of rat anti-mouse IFN-gamma monoclonal antibody was carried out. Anti-mouse IFN-gamma monoclonal antibody neutralized endogenous IFN-gamma and resulted in the suppression of the number of granulomas and the size of each granuloma. These findings suggest that biphasic production of endogenous IFN-gamma in the local lesions may be crucial to the formation and development of the granulomas. PMID- 8514391 TI - Pneumocystis carinii is not universally transmissible between mammalian species. AB - In a series of five experiments, we attempted to transmit Pneumocystis carinii from ferrets to SCID mice by intratracheal inoculation. Using highly specific and sensitive assay techniques, we could not document infection of SCID mice by P. carinii isolated from ferrets. In contrast, under identical inoculation conditions, P. carinii was easily transmissible from one SCID mouse to another. These results indicate that P. carinii organisms, at least those isolated from ferrets, have a restricted host range. The finding of restricted transmission of P. carinii is consistent with the increasing evidence for host species-specific antigenic variation among isolates of P. carinii. If restricted host range is a consistent biological feature of animal-derived P. carinii, it would suggest that P. carinii pneumonitis in humans may not be a zoonosis as previously speculated. PMID- 8514392 TI - Investigation of the influences of puberty, genetics, and environment on the composition of subgingival periodontal floras. AB - The classical twin model was utilized in this study in an attempt to determine the importance of host genetics to the composition of the subgingival flora. Simultaneously, the effect of puberty on the flora composition was assessed. The compositions of the floras were significantly different at ages 11 and 14 in the same people, indicating that transition to an adult flora composition may be initiated during puberty. However, the numbers of subjects who had prepubertal and postpubertal testosterone levels in this study were too small to demonstrate significant differences based solely on testosterone level (P = 0.053 and 0.11 for tests of unrelated members, i.e., all twins "a," the first twin of each pair, and all twins "b," the second twin of each pair). Sixteen unrelated 11-year-old subjects had prepubertal levels of less than 30 ng of testosterone per dl of serum, and only six of these unrelated subjects had levels above 300 ng/dl by age 14. Of their twin siblings, who formed the second group of unrelated individuals, 15 had prepubertal levels and only 5 reached postpubertal levels. Unpaired t tests indicated that Veillonella atypica, Prevotella denticola, and Prevotella melaninogenica were among the species that contributed most to changes in flora composition during puberty. The compositions of subgingival floras of 11-year-old monozygous and dizygous male twins were significantly more similar than those of unrelated subjects in the study (P = 0.004 and 0.009, respectively). At 12.5 years of age, the floras of monozygous twins remained more similar than those of unrelated subjects (P = 0.001), but the dizygous-twin floras were not significantly more similar than those of unrelated people. This difference corresponded with moderate and varied testosterone levels within dizygous-twin pairs at age 12.5. By age 14 both monozygous and dizygous twins again had floras with compositions more similar than those of unrelated people (P = 0.008 and 0.002, respectively). Estimates of the genetic contributions to the increased similarity of the floras of twins as compared with floras of unrelated people indicated that the concentrations of several species in the flora may be influenced by host genetic factors. The prevalence of certain other species appeared to be controlled primarily by environment. PMID- 8514393 TI - Antigenicity and immunogenicity of a synthetic peptide derived from a glucan binding domain of mutans streptococcal glucosyltransferase. AB - The immunogenicity and antigenicity of a multiply antigenic peptide construct containing four copies of the synthetic peptide TGAQTIKGQKLYFKANGQQVKG were measured in rodents and humans, respectively. The composition of this peptide construct (termed GLU) was derived from a major repeating sequence in the C terminal region of mutans streptococcal glucosyltransferases that synthesize water-insoluble glucan (GTF-I). The GLU peptide elicited high levels of serum immunoglobulin G antibody to GLU after subcutaneous injection into Sprague-Dawley rats. These antisera also reacted with intact GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (by enzyme-linked immunosorbent assay [ELISA] and Western blot [immunoblot] analyses) and with an 87-kDa glucan-binding protein from S. sobrinus (by Western blot). The synthesis of filter-retained glucan by GTF-Sd of S. sobrinus could be inhibited (30%) by preincubation with anti-GLU rat serum. Splenic and lymph node lymphocytes from rats injected once with S. sobrinus GTF isozymes demonstrated significant proliferation after 5 days of culture with GLU. The GLU peptide reacted with 4 of 29 human parotid saliva samples and 5 of 29 human serum samples (by ELISA). These results suggest that the GLU peptide contains B- and T-cell epitopes that are similar to those of intact mutans streptococcal GTFs and possibly certain other glucan-binding proteins as well. Furthermore, since antibody to this epitope(s) appears to inhibit GTF function, sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine. PMID- 8514394 TI - The RTX cytotoxin-related FrpA protein of Neisseria meningitidis is secreted extracellularly by meningococci and by HlyBD+ Escherichia coli. AB - Neisseria meningitidis produces proteins (FrpA and FrpC) related to the RTX cytotoxin family. In meningococcal strain FAM20 these proteins were both localized in the outer membrane and secreted into the extracellular medium. An Escherichia coli strain with wild-type hemolysin secretion genes hlyB and hlyD and containing a cloned frpA gene secreted FrpA, whereas an isogenic hlyBD mutant strain did not. Low-stringency DNA hybridization revealed hlyBD-like sequences in N. meningitidis FAM20, suggesting that a similar RTX secretion system exists in meningococci. Structural features found at the C termini of other RTX proteins and thought to be important for their secretion were also found at the C terminus of FrpA. The secretion of FrpA from E. coli by heterologous RTX transport proteins further demonstrates the relation of the FrpA protein to RTX toxins. PMID- 8514395 TI - Purification and characterization of alpha-toxin produced by Clostridium novyi type A. AB - Our study describes the production, purification, and properties of alpha-toxin from Clostridium novyi type A 19402. The bacterium produced maximal amounts of alpha-toxin when grown at 37 degrees C for 72 h in dialysis flask cultures containing brain heart infusion supplemented with 0.75% Tween 80 and 2% glycerol. The alpha-toxin was purified by precipitation with polyethylene glycol 6000, followed by chromatography on Q-Sepharose, phenyl-agarose, and Mono-Q. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the toxin exhibited a single band with an M(r) of 200,000. The toxin also exhibited a single immunoprecipitin arc by crossed immunoelectrophoresis with antiserum against crude toxin. It was stable when stored at 4 degrees C and also following exposure to buffers with pHs in the range of 4 to 7. The toxin had a minimum lethal dose in mice of 5 to 10 ng, caused rounding of a variety of cells in tissue culture, and was negative in the rabbit ileal loop assay. The cytotoxic activity was inhibited by agents that affect receptor-mediated processes, and the toxin was less active on a CHO mutant cell line that is defective in endosomal acidification. The analysis of the amino acid composition revealed an unusually high proline content. The N-terminal sequence is Met-Leu-Ile-Thr-Arg-Glu-Gln-Leu-Met-Lys. PMID- 8514396 TI - The intracellular bacterium Rhodococcus equi requires Mac-1 to bind to mammalian cells. AB - Rhodococcus equi is a facultative intracellular bacterium of macrophages that causes disease in immunocompromised individuals, particularly those with AIDS. In this report, we demonstrate that R. equi binding to mammalian cells requires complement and is mediated primarily by the leukocyte complement receptor, Mac-1. Bacteria bind to macrophages poorly unless exogenous complement is added to the incubation medium. The addition of fresh nonimmune serum, which contains no detectable antibodies to R. equi, greatly enhances bacterial binding to macrophages, whereas heat inactivation of this serum or immunological depletion of C3 from the serum reduces binding to levels only slightly higher than those of binding under serum-free conditions. Human serum depleted of C2 or C4 is fully opsonic, indicating that complement activation and fixation occur by the alternative pathway. The serum-dependent binding of rhodococci to macrophages is mediated primarily by the macrophage complement receptor type 3, Mac-1 (CD11b/CD18). Bacteria do not bind to fibroblastoid or epithelial cells that lack this receptor. Most of the bacterial binding to macrophages is inhibited by a monoclonal antibody to Mac-1 but is unaffected by a monoclonal antibody to complement receptor type 1. Furthermore, opsonized, but not unopsonized, bacteria bind to purified Mac-1 immobilized on plastic. In addition, in the presence of opsonic complement, rhodococci bind efficiently to fibroblastoid cells transfected with cloned Mac-1 but relatively poorly to cells transfected with the complement receptor type 1. Hence, R. equi fixes complement by activating the alternative complement pathway, and this fixation is a requirement for bacterial adhesion and invasion. Furthermore, complement fixation defines rhodococcal host cell tropism, since R. equi binds specifically and exclusively to cells expressing Mac-1. PMID- 8514397 TI - A Campylobacter jejuni homolog of the LcrD/FlbF family of proteins is necessary for flagellar biogenesis. AB - A Campylobacter jejuni homolog of the lcrD/flbF family of genes was cloned and sequenced. The nucleotide sequence of the gene, called flbA, predicted a protein of 78,864 Da, with significant homology to a group of related proteins including the Yersinia pestis LcrD, Salmonella typhimurium InvA, and Caulobacter crescentus FlbF proteins. The greatest homology was seen with the C. crescentus FlbF protein, with an overall amino acid sequence homology of 57%. An insertion mutation in the C. jejuni 81-176 flbA gene was constructed. The resultant strain did not synthesize flagellin and was nonmotile. PMID- 8514398 TI - Variant cysteine-rich surface proteins of Giardia isolates from human and animal sources. AB - Cloned Giardia isolates obtained from a sheep, a calf, and a human possessed a major membrane protein that showed marked intraspecific variations in size as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis following surface biotinylation and radioiodination. Metabolic labeling with [35S] cysteine and electrophoretic analysis also revealed for each cloned isolate a predominant protein that corresponded in size to the major surface protein demonstrated by surface labeling techniques. Immunoprecipitation studies with a polyclonal antiserum specifically directed against the 90-kDa major cysteine-rich protein purified from a subclone of the sheep isolate (O2-4A1) showed that the cysteine-rich protein and the major surface protein are identical. The surface location of the antigen was further corroborated by the reaction of fluorescence labeled antibodies raised against the 90-kDa O2-4A1 cysteine-rich protein with the entire surface of live trophozoites of the homologous clone. The ability of the cloned Giardia isolates to undergo variations of their cysteine-rich surface protein (CRISP) was demonstrated by the spontaneous appearance of new CRISPs in clonally derived populations during prolonged in vitro culturing and in cultures of the O2-4A1 clone that had survived treatment with the cytotoxic anti-90-kDa CRISP antiserum specific for the surface antigen of this clone. The surviving progeny were devoid of the original CRISP, as judged by resistance to the immune serum. Subsequent cysteine metabolic labeling of the recloned surviving trophozoites demonstrated a large number of new variants, each expressing a single CRISP that varied significantly in molecular weight from those in the different cloned lines. These studies suggest that the presence of CRISPs and their variations are not restricted to Giardia isolates obtained from humans but are universal phenomena among the Giardia duodenalis types of organisms. PMID- 8514399 TI - Cytoadhesins of Mycoplasma hominis. AB - The mechanism of Mycoplasma hominis adherence to host cells of the urogenital tract was investigated with monoclonal antibodies (MAbs) directed against antigenic surface-localized polypeptides P50, P60, P80, and P100 of cytoadherent M. hominis FBG. A cell enzyme-linked immunosorbent assay was established allowing quantification of cytoadherent mycoplasmas detected by one of the following MAbs: four MAbs directed against P100 (molecular weight, about 100,000), three MAbs against P80, one MAb against P60, and three MAbs against P50. MAb binding to one of the surface proteins resulted in a decrease of mycoplasmal adherence to HeLa cells. To exclude the thesis that this is caused by nonspecific blocking of adherence, P100 and P50 were purified by affinity chromatography and tested instead of intact mycoplasmas in the cell enzyme-linked immunosorbent assay for cytoadherence. Both proteins bound to the surface of the eukaryotic cells. MAb binding to single epitopes of these proteins resulted in inhibition of protein adherence. These experiments strongly suggest that of the four surface-localized proteins at least P100 and P50 are adhesins of M. hominis FBG. PMID- 8514400 TI - Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. AB - Leishmaniae are protozoans which, depending upon both the host and parasite species, can cause either a healing or nonhealing infection. While C57BL/10 mice are able to heal following infection with Leishmania major, they fail to heal following infection with Leishmania amazonensis. In order to address the role of Th1 and Th2 cell responses in the outcome of these infections in C57BL/10 mice, gamma interferon (IFN-gamma) and interleukin-4 (IL-4) production was assessed. While cells from L. major-infected C57BL/10 mice produced high levels of IFN gamma, cells from L. amazonensis-infected animals produced little or no IFN gamma. On the other hand, IL-4 was produced only by cells from L. amazonensis infected C57BL/10 mice, but this production was restricted to the first few weeks of infection. Later in infection, when lesions were evident, no IL-4 was detected. Treatment of BALB/c mice with a monoclonal antibody (11B11) directed against IL-4 induced a dramatic reduction in L. amazonensis lesions. This reduction was associated with a decrease in IL-4 levels and an increase in IFN gamma production. However, only a slight reduction in lesion sizes and parasite numbers was observed when anti-IL-4-treated C57BL/10 mice were infected with L. amazonensis. These results suggest that IL-4 may have an important role in mediating susceptibility to L. amazonensis in BALB/c mice, as previously demonstrated for L. major. More importantly, however, the data suggest that susceptibility to L. amazonensis in C57BL/10 mice is due to the absence of a Th1 cell response, rather than to the presence of a Th2 cell response. PMID- 8514401 TI - Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. AB - Incubation of encapsulated cells of Cryptococcus neoformans in normal human serum leads to activation of the alternative complement pathway and deposition of opsonic fragments of C3 into the capsule. We determined whether the variation in capsular structure that occurs among the four major cryptococcal serotypes was reflected in the kinetics for activation and binding of C3. We also examined the effects on activation kinetics of de-O-acetylation or periodate oxidation of the capsule. Binding kinetics were characterized in terms of the time required to deposit 5% of the maximal amount of C3 on the yeast (t5%), the first-order rate constant for amplification of C3 deposition (k'), and the maximum amount of C3 that could be deposited in the capsule (C3max). Our results showed that variations in the capsular structure that characterized each serotype had no significant influence on C3max but that the rate of C3 deposition depended significantly on the serotype. C3 accumulated at a higher rate on cells of serotypes A and D than on cells of serotypes B and C. There was a significant correlation between capsular volume and C3max, although the relationship was not linear. Periodate treatment of encapsulated cryptococci of all four serotypes led to decapsulation. Periodate-oxidized encapsulated cells displayed kinetics for activation and binding of C3 that were identical to kinetics observed with nonencapsulated cryptococci. Finally, de-O-acetylation led to a significant but relatively minor increase in C3max. PMID- 8514402 TI - Purification of exfoliative toxin produced by Staphylococcus hyicus and its antigenicity. AB - We previously reported the isolation of an exfoliative toxin from culture filtrates of Staphylococcus hyicus (shET) and reproduction of exfoliation in piglets injected with partially purified shET. In this study, we purified shET and compared the biological and physicochemical properties of shET and Staphylococcus aureus exfoliative toxin (sETA and sETB). shET was purified by ammonium sulfate precipitation, DEAE-cellulofine A-500 column chromatography, Sephadex G-75 gel filtration, and polyacrylamide gel electrophoresis (7.5% polyacrylamide). Purified shET (p-shET) did not cause exfoliation of the epidermis in suckling mice but did cause exfoliation in 1-day-old chickens, whereas sETA and sETB produced by S. aureus caused exfoliation in suckling mice but not in 1-day-old chickens. The molecular mass of p-shET was determined as 27 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. p-shET did not show any cross-reactivity with sETA and sETB in Western immunoblotting analysis or the immunodiffusion test. PMID- 8514403 TI - Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine. AB - Cecropin P1 and PR-39 are two antibacterial peptides isolated from the upper part of the small intestine of the pig. They have been sequenced, and their antibacterial spectra have been investigated (J.-Y. Lee, A. Boman, C. Sun, M. Andersson, H. Jornvall, V. Mutt, and H. G. Boman, Proc. Natl. Acad. Sci. USA 86:9159-9162, 1989; B. Agerberth, J.-Y. Lee, T. Bergman, M. Carlquist, H. G. Boman, V. Mutt, and H. Jornvall, Eur. J. Biochem. 202:849-854, 1991). We have now compared these two peptides for their mechanism of action on Escherichia coli K 12 by using three strains with different markers. Our results show that cecropin P1, like other cecropins, kills bacteria by lysis and that this reaction requires more peptide to kill more cells. PR-39 requires a lag period of about 8 min to penetrate the outer membrane of wild-type E. coli; then killing is quite fast. This lag period was absent in the envA1 mutant; in this strain the outer membrane was freely permeable to both peptides. PR-39 killed growing bacteria faster than nongrowing cells; for cecropin P1 there was no such difference. It is suggested from isotope incorporation experiments that PR-39 kills bacteria by a mechanism that stops protein and DNA synthesis and results in degradation of these components. PMID- 8514404 TI - In utero transmission of Mycoplasma pulmonis in experimentally infected Sprague Dawley rats. AB - Genital mycoplasmosis is important as an animal model for the interaction between infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects in which the rat is used as a model to study reproductive function and physiology. We report the in utero transmission of Mycoplasma pulmonis and the development of placentitis, amnionitis, and mild fetal bronchopneumonia in Sprague-Dawley rats. A minimum of 10 days prior to breeding, specific-pathogen-free female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of M. pulmonis X1048 or with an equal volume of sterile broth. Rats and fetuses were subjected to necropsy at days 11, 14, and 18 of gestation. M. pulmonis was able to invade the placenta, cross the placental barrier, and establish an amniotic fluid infection by gestational day 14. It was isolated from the oropharynx and lungs of fetuses at gestational day 18. The placenta was more frequently colonized than amniotic fluid, followed by the fetal oropharynx and lungs, supporting an ascending route of infection. Histopathological evidence also support an active infection, with lesions compatible with placentitis, amnionitis, and mild fetal bronchopneumonia. M. pulmonis can traverse the placenta, resulting in infection of the amniotic fluid and in utero transmission of the microorganism to the developing fetus. PMID- 8514405 TI - Selective inhibition of microbial serine proteases by eNAP-2, an antimicrobial peptide from equine neutrophils. AB - Equine neutrophil antimicrobial peptide 2 (eNAP-2), a recently described antimicrobial peptide isolated from equine neutrophils, was found to selectively inactivate microbial serine proteases (subtilisin A and proteinase K) without inhibiting mammalian serine proteases (human neutrophil elastase, human cathepsin G, and bovine pancreatic trypsin). Although the primary structure of eNAP-2 resembled that of several known antiproteases that belong to the 4-disulfide core peptide family, this pattern of selectivity is unique. eNAP-2 formed a noncovalent complex with native subtilisin A or proteinase K but did not associate with these enzymes if they had been treated with phenylmethylsulfonyl fluoride, a serine protease inhibitor. The eNAP-2-microbial protease complex was disrupted by boiling or by exposure to low pH. We suggest that eNAP-2 exerted selective antiproteinase activity by binding tightly but noncovalently to the active site of subtilisin A or proteinase K. Since microbial exoproteases may act as virulence factors, the combined antimicrobial and antiprotease activities of eNAP-2 could allow it to play an important role in neutrophil-mediated antimicrobial defenses. PMID- 8514406 TI - Bovine polymorphonuclear leukocyte killing of Tritrichomonas foetus. AB - The role of bovine antibody and complement in bovine neutrophil-mediated killing of Tritrichomonas foetus was investigated. No neutrophil-mediated trichomonacidal activity was detected when Hanks' balanced salt solution, a widely utilized and weakly buffered medium, was used. This lack of neutrophil activity was evident even in the presence of specific bovine antibody and bovine complement. Moreover, the pH of the weakly buffered Hanks' balanced salt solution was observed to fall from pH 7.0 to 5.8 in 4 h at 37 degrees C in the presence of T. foetus. The pH of 5.8 inhibited the bactericidal activity of bovine neutrophils for Staphylococcus epidermidis by 53.2% and may have contributed to the lack of neutrophil-mediated trichomonacidal activity in the weakly buffered salt solution. However, T. foetus was susceptible to bovine neutrophil-mediated destruction when a HEPES (N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered Hanks' balanced salt solution was used (21.8% killing by neutrophils alone). Neither specific bovine immune serum nor purified immune bovine immunoglobulin G2 alone enhanced bovine neutrophil-mediated killing. When complement-sensitized trichomonads were incubated with bovine neutrophils, killing of T. foetus was observed, a result which represented the additive effects of each treatment. Significant (P < 0.05) killing of trichomonads was observed when antibody- and complement-opsonized trichomonads were exposed to bovine neutrophils (> 70% parasite destruction), an effect which reflected the additive nature of each treatment. PMID- 8514407 TI - Isotype responses to candidate vaccine antigens in protective sera obtained from mice vaccinated with irradiated cercariae of Schistosoma mansoni. AB - In experimental schistosomiasis, sera of mice multiply vaccinated with radiation attenuated cercariae of Schistosoma mansoni passively transfer resistance against cercarial challenge to naive mice. To further characterize these sera, we tested their protective capacities in two mouse strains (C57BL/6J and CBA/J) and compared the antigen-specific isotype compositions of the different protective sera by means of the enzyme-linked immunosorbent assay. By using an array of purified schistosomal antigens, the patterns of antibody titers and isotypes differed for each experimental group and antigen. In the most-protective C57BL/6J sera, high levels of immunoglobulin G1 (IgG1), IgG2a, and IgG2b bound to heat shock protein 70 and the integral membrane protein Sm23, whereas recognition of these antigens by less-protective CBA/J sera was lower. Glutathione S-transferase (GST) was recognized predominantly by IgM antibodies of all vaccinated groups, and a significant portion of this response was directed against carbohydrate epitopes. Antibodies specific for triosephosphate isomerase, paramyosin, and Sm32 (hemoglobinase) were present in less-protective sera and thus seem less relevant for passive transfer of resistance. The results of this study suggest a contribution of IgG antibodies specific for heat shock protein 70 and Sm23, and possibly a contribution of GST-specific IgM antibodies, to the protective effect of sera from C57BL/6J mice vaccinated with irradiated cercariae. PMID- 8514408 TI - Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and induces production of gamma interferon. AB - We studied the capacity of glutaraldehyde-fixed Helicobacter pylori to stimulate natural killer (NK) cell activity. Bacteria were incubated overnight with peripheral blood lymphocytes enriched for large granular lymphocytes (LGL), the mediators of non-major histocompatibility complex-restricted cellular cytotoxicity. Then, the cytolytic activity of LGL was tested against various tumor target cells. We observed that efficient cytolytic activity was generated against resistant and nonresistant tumor target cell lines. Nine local clinical isolates of H. pylori and the reference strain NCTC 11637 were tested, and they all were equally effective in inducing NK cell activity. However, flagellin antigen, glycine extract, urease, and lipopolysaccharide prepared from H. pylori NCTC 11637 all failed to induce significant NK cell activity. The supernatants which were collected after coincubation of bacteria with LGL contained a factor(s) which could activate resting LGL into efficient cytolytic activity. The supernatants were also analyzed for interferon (IFN) activity. We observed that high titers of IFN were produced and that IFN activity was neutralized with anti gamma interferon (IFN-gamma) antiserum, but not with anti-IFN-alpha antiserum. Thus, contact of lymphocytes with H. pylori leads to efficient stimulation of NK cell activity and the production of IFN-gamma. PMID- 8514409 TI - Protein D of Haemophilus influenzae is not a universal immunoglobulin D-binding protein. AB - Haemophilus influenzae type b and nontypeable H. influenzae have been reported to bind human immunoglobulin D (IgD). IgD myeloma sera from five patients were tested for the ability of IgD to bind to H. influenzae. Serotype b strains bound human IgD in four of the five sera tested. IgD in the fifth serum bound strongly to type b strain MinnA but poorly to other type b strains. Additionally, IgD binding was not observed when nontypeable strains were tested. The gene for protein D, the putative IgD-binding protein, was cloned from the IgD-binding H. influenzae type b strain MinnA and expressed in Escherichia coli. IgD binding to E. coli expressing protein D was not demonstrable. Recombinant protein D was purified, and antisera were generated in rabbits. Using these rabbit sera, we detected protein D in nontypeable as well as serotype b strains by Western blotting (immunoblotting). In contrast, IgD myeloma protein 4490, which was previously reported to bind to protein D by Ruan and coworkers (M. Ruan, M. Akkoyunlu, A. Grubb, and A. Forsgren, J. Immunol. 145:3379-3384), bound strongly to both type b and nontypeable H. influenzae as well as to E. coli expressing protein D. Thus, IgD binding is a general property of H. influenzae type b strains but not a general property of nontypeable strains, although both type b and nontypeable strains produce protein D. With the exception of IgD myeloma protein 4490 binding, we have no evidence for a role of protein D in IgD binding to H. influenzae. PMID- 8514410 TI - Nucleotide sequence encoding the mannose-fucose-resistant hemagglutinin of Vibrio cholerae O1 and construction of a mutant. AB - The region of DNA encoding the mannose-fucose-resistant hemagglutinin (MFRHA) of Vibrio cholerae O1 has been localized, and the nucleotide sequence has been determined. The region contains a single open reading frame encoding 230 amino acids, corresponding to a protein of 26.9 kDa. The N terminus of this protein is atypical for a protein localized in the outer membrane. A mutant lacking MFRHA activity has been constructed by allelic exchange after inactivation via the insertion of a kanamycin resistance gene cartridge. The MFRHA-negative mutant has been assessed for virulence in the infant mouse cholera model. This mutant shows a marked defect in its ability to persist in the infant mouse gut and is incapable of competing with the wild-type organism, even when given in 25-fold excess. This defect also leads to a > 100-fold increase in the 50% lethal dose. These data suggest that the MFRHA is an important colonization factor in the infant mouse model. PMID- 8514411 TI - Antimicrobial proteins of murine macrophages. AB - Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. PMID- 8514413 TI - Multiplication of Listeria monocytogenes in a murine hepatocyte cell line. AB - Listeria monocytogenes was shown to invade and multiply in a murine hepatocyte cell line (ATCC TIB73). Hemolytic and nonhemolytic L. monocytogenes strains exhibited similar abilities to invade hepatocytes, but only hemolytic L. monocytogenes multiplied within this cell line. Microscopic evaluation of monolayers stained with Wright stain demonstrated focal necrosis (plaques) in the hepatocyte monolayers, with large numbers of intracellular listeriae visible within the hepatocytes that lined the margins of these plaques. Murine recombinant interleukin-1 alpha, human recombinant tumor necrosis factor alpha, and murine recombinant gamma interferon did not affect the multiplication of L. monocytogenes in the hepatocytes. These data confirm in vivo observations of the intracellular multiplication of L. monocytogenes in hepatic lesions in infected mice. PMID- 8514412 TI - Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans. AB - We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols. PMID- 8514414 TI - Detection of a prfA-independent promoter responsible for listeriolysin gene expression in mutant Listeria monocytogenes strains lacking the PrfA regulator. AB - Expression of listeriolysin, a major virulence factor of pathogenic Listeria monocytogenes, is positively regulated by the pleiotropic virulence regulator PrfA. In this study, we demonstrate that L. monocytogenes strains lacking the prfA regulator gene produce listeriolysin in small, albeit detectable, amounts when analyzed in a hemolysin assay and by immunoblots with listeriolysin-specific monoclonal antibodies. Transcriptional analysis revealed the existence of a PrfA independent promoter that was responsible for the hemolytic activity expressed by these strains. PMID- 8514415 TI - Species of alpha-hemolytic streptococci possessing a C-polysaccharide phosphorylcholine-containing antigen. AB - An enzyme-linked immunosorbent assay technique was used to detect and quantify C polysaccharide-like antigen in strains of alpha-hemolytic streptococci classified into species by following the latest taxonomic recommendations. C-polysaccharide like antigen is found only in Streptococcus oralis, S. mitis, and S. pneumoniae, which are genetically closely related. PMID- 8514416 TI - Lack of allelic polymorphism for the major outer membrane protein gene of the agent of guinea pig inclusion conjunctivitis (Chlamydia psittaci). AB - The major outer membrane protein gene (omp1) was sequenced for each of six Chlamydia psittaci (guinea pig inclusion conjunctivitis [GPIC]) strains isolated from guinea pigs. Five of the isolates were obtained in the United States during the 1960s and 1970s, including the prototype strain isolated by Murray in 1962. The other isolate was obtained from a guinea pig in England. The nucleotide sequence of the omp1 gene for each strain was identical. The lack of omp1 allelic polymorphism among GPIC isolates suggests that, unlike C. trachomatis, the GPIC agent lacks antigenic variation in the major outer membrane protein. PMID- 8514417 TI - Antimicrobial activity of two bactenecins against spirochetes. AB - Bac5 and Bac7 are antimicrobial peptides of bovine neutrophils that act on enteric gram-negative bacteria. We report here that these two peptides immobilize and kill Leptospira interrogans and Leptospira biflexa with MBCs of 6 to 25 micrograms/ml. Conversely, although both peptides bind to Borrelia burgdorferi, the organism is resistant to their action. PMID- 8514418 TI - Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. AB - The study of the effects of osmolarity and growth phase on Salmonella typhi adherence to and invasion of Henle 407 epithelial cells provides the first evidence of a clear overlap between these two environmental stimuli. High osmolarity conditions are required in the late-log phase for optimum induction of the adherent and invasive phenotypes. PMID- 8514419 TI - Amino-terminal sequence analysis of the Coccidioides immitis chitinase/immunodiffusion-complement fixation protein. AB - A chitinase isolated from Coccidioides immitis was subjected to amino-terminal protein sequence analysis. The resulting 18-amino-acid sequence was compared with the previously reported amino acid sequence of coccidioidal immunodiffusion complement fixation (IDCF) antigen. From the homology of the two sequences, the results support the identification of the IDCF antigen with a chitinase. PMID- 8514420 TI - Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice. AB - Organisms of the Mycobacterium avium complex are associated with disseminated infection in patients with AIDS. The mechanisms that account for the survival of the intracellular bacteria are unknown. We document here that infection of C57BL/6 black mice with M. avium 101 triggered interleukin-10 (IL-10) production. The synthesis of IL-10 peaked after 2 weeks of infection and remained elevated throughout the period of infection. Treatment of M. avium-infected peritoneal macrophages with recombinant IL-10 suppressed the stimulatory effect of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. To confirm the possible role of IL-10 in the infection in vivo, mice were infected with M. avium 101 and simultaneously received treatment with neutralizing anti-IL 10 antibody. After 4 weeks the animals were harvested and the numbers of viable bacteria were quantitated in the liver, spleen, and blood. The liver and spleen of animals receiving anti-IL-10 antibody had 2 to 3 log units fewer bacteria than did those of control animals. These results suggest a role for IL-10 in the pathogenesis of M. avium infection. PMID- 8514421 TI - Inhibition of T-cell responsiveness during experimental infections with Trypanosoma brucei: active involvement of endogenous gamma interferon. AB - Lymph node cells (LNC) from mice infected with Trypanosoma brucei contain macrophage-like cells that inhibit interleukin-2 receptor (IL-2R) expression (M. Sileghem, A. Darji, R. Hamers, M. Van De Winkel, and P. De Baetselier, Eur. J. Immunol. 19:829-835, 1989). Evidence that gamma interferon (IFN-gamma) is actively involved in (i) the inhibition of IL-2R expression and (ii) the generation of suppressive cells during infections with T. brucei is presented. First, despite an impaired T-cell mitogenic response, LNC from infected mice are hyperresponsive for IFN-gamma production. Second, addition of neutralizing anti IFN-gamma antibodies to cocultures of normal LNC and suppressive LNC populations reduces the level of suppression and restores the level of IL-2R expression. Third, administration of anti-IFN-gamma to T. brucei-infected animals increases the blastogenic response and reduces the suppressive activity of LNC. PMID- 8514423 TI - Platelet-activating factor acetylhydrolase in the male reproductive tract: origin and properties. AB - The properties and origin of platelet-activating factor acetylhydrolase- (PAF-AH) like activity in the male reproductive tract were investigated. Seminal plasma (SP) and serum were obtained from normal donors and infertile patients while prostatic fluid (PF), seminal vesicle fluid (SVF) and vas deferens fluid were collected at autopsy. PAF-AH-like activity was found in all fluids tested. The specific activity of the enzyme in SP and PF was twice that of PAF-AH in serum and 15-fold higher than that in SVF and vas deferens fluid. In SP, PAF-AH-like activity was Ca(++)-independent, acid and heat labile, stable to freezing, not inhibited by phosphatidylcholine, but was inhibited by 10 mM disopropylfluorophosphate (DFP) and 13 mM phenylmethylsulfonylfluoride (PMSF). These data indicate that the properties of the enzyme in SP are similar to those reported for PAF-AH in serum. The variation in specific activity of PAF-AH in reproductive tract fluids suggest that there are either activators of PAF-AH in SP or inhibitors in one or several of the other reproductive tract fluids. PMID- 8514422 TI - Predictive value of morphologically normal sperm concentration in the medium for in-vitro fertilization. AB - Morphological evaluation of spermatozoa using strict criteria (MEUSC) and conventional sperm parameters were studied with respect to in-vitro fertilization and pregnancy outcome before and after a swim-up selection procedure. Recovered oocytes were inseminated with 50,000 progressively motile spermatozoa, and this study assess the influence of the total number of spermatozoa and of the percentage with strictly normal morphology in the insemination sample on the outcome of IVF. The results showed that the percentages of spermatozoa with normal morphology using strict criteria, both in native and in post-swim-up samples, were the best predictors of IVF outcome. Their respective cut-off points were 5% and 8%. The number of morphologically normal spermatozoa inseminated also showed a good correlation with fertilization. However, it was not possible to find a proper cut-off point for this parameter. The patients were categorized on the basis of their native and post-swim-up scores. Category 1, in which both parameters were below their respective cut-off points, showed a 7% fertilization rate and a 0% pregnancy rate. Category 3, in which both parameters were above their cut-off points, showed a 70% fertilization rate and a 23% pregnancy rate. This suggests that sperm morphology can be used as a criterion for patient selection for IVF as an aid to identification of possibly subfertile males. PMID- 8514424 TI - A search for circulating immunoglobulins blocking follicle-stimulating hormone action in male idiopathic infertility. AB - In this study, patients with idiopathic infertility were investigated for the presence of circulating antibodies which interfered with follicle-stimulating hormone (FSH) activity. A retrospective search for autoantibodies was undertaken using single plasma samples obtained from 29 infertile men with azoo/oligo/asthenoteratozoospermia and eight controls with normozoospermia and normal blood FSH levels. Plasma levels of immunoactive FSH, bioactive FSH, immunoactive luteinizing hormone and testosterone were measured in the individual samples. Plasma immunoglobulin G (IgG) was isolated using protein-A chromatography and tested at different dose levels for its ability to inhibit and/or stimulate basal and FSH-induced aromatase activity in immature rat Sertoli cells in vitro. In the first set of trials, IgGs isolated from three infertile patients showed apparent inhibition of FSH-stimulated aromatase activity, two showed further stimulation and five showed irregular fluctuations beyond the normal range of stimulation. When reanalysed at different doses, none of the IgG fractions exhibited abnormal interference with FSH action. It is concluded that, unlike many other endocrine disorders characterized by autoimmunity, the occurrence of autoantibodies of the IgG class blocking FSH action in male infertility is improbable. PMID- 8514425 TI - Qualitative assessment of thermal and evaporative adjustments of human scrotal skin in response to heat stress. AB - To study scrotal thermoregulation and its efficacy to work against heat accumulation, five subjects were exposed to four experimental conditions under which core and skin temperatures and sweat evaporative responses of various skin surfaces--chest, abdomen and scrotum--were compared. The temperature response of the scrotal area exhibited the largest inertia, and this observation is likely to be the consequence of heat exchange via the vascularization of testes and scrotum which is more efficient than in other parts of the body in limiting local heat storage, thus alleviating heat stress of the testis. The pulsatile nature and the synchronous pattern of the scrotal evaporative heat loss indicate that scrotal sweating takes place, although the gradient response appeared to be less marked than elsewhere in the body. Relatively low and inert scrotal temperature can partly explain this poor local drive for sweating. PMID- 8514426 TI - Paternity in a patient with testicular seminoma and contralateral testicular intraepithelial neoplasia. AB - A 32-year-old patient with unilateral beta hCG-positive seminoma and contralateral testicular intraepithelial neoplasia (TIN; so-called carcinoma-in situ) with no metastases (clinical stage I) received one course of adjuvant carboplatin therapy. He refused further treatment of TIN in his remaining testis. His wife became pregnant by him 4 months later and delivered a healthy child at term. This case shows that patients with TIN in their remaining solitary testis are not necessarily infertile, and testes afflicted with TIN must also contain tubules that retain normal spermatogenic potential. Surveillance may be an treatment option for patients with TIN in their remaining testis in cases where there is a strong desire for paternity. PMID- 8514427 TI - Developmental expression and androgen regulation of 24 kDa secretory proteins by the murine epididymis. AB - Two peptides with a molecular weight of 24 kDa and a P(i) of 8.4-8.8 were found to be synthesized and secreted specifically by the caput epididymis of adult male mice under androgen control. The peptides can interact with spermatozoa. In the present study, the developmental pattern of [35S]-methionine-labelled proteins synthesized by the murine caput epididymis at 10, 20, 30 and 40 days of age were studied using two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and autoradiography. Active synthesis of the 24 kDa proteins was detected in the epididymis from 20 days of age, but secretion of the two peptides was only observed from 30 days of age onwards. To determine whether androgens influenced the active expression of 24 kDa proteins in the developing epididymis, their effect on [35S]-methionine incorporation into proteins was assessed using 2D PAGE. Mice were either castrated, castrated then testosterone injected or simply testosterone injected at 10, 20, 30 or 40 days of age. Androgen control of 24 kDa protein expression was also studies in vitro in epididymal organ culture over a 10-day period, with or without testosterone. Androgens were not involved in the initiation of synthesis of the 24 kDa proteins from days 10 to 20, as shown by in vivo and in-vivo experiments. However, androgens appeared to be essential for maintaining synthesis and secretion of the proteins from 20 days of age onwards. Administration of excessive testosterone was only able to increase secretion of the 24 kDa proteins in intact male mice aged 40 days. PMID- 8514428 TI - Serum levels of testosterone and oestrogens in normal and infertile stallions. AB - The serum concentrations of testosterone and oestrogens were determined in stallions classified as geldings, normal (according to age) or infertile (azoospermic). There were significant differences in testosterone and oestrogen levels between the groups. Normal concentrations of testosterone and total oestrogens were attained after 16 months of age. Castrated and immature horses (< 15 months of age) had lower levels of testosterone and total oestrogens than did mature and infertile stallions. Azoospermic stallions had lower levels of testosterone and total oestrogens than did normal mature horses except in one case (B4) in which the level of total oestrogens was increased markedly. Critical ellipses for testosterone and total oestrogens were obtained for both groups (6 15-month-old colts and stallions aged > 4 years). The results suggest that serum levels of testosterone and total oestrogens may provide a sensitive index of the endocrine function of the testis in male horses. PMID- 8514429 TI - Interleukin-1 bioactivity and DNA synthesis in X-irradiated rat testes. AB - Stage-specific DNA synthesis and interleukin-1 (IL-1) bioactivity were measured in the rat testis at 2, 6, 12 and 25 days after local irradiation with 3 Gy to investigate whether there was any correlation between germ cell DNA synthesis during repopulation and IL-1-like bioactivity in the seminiferous epithelium. DNA synthesis by intermediate and type-B spermatogonia was reduced significantly at 2, 6 and 12 days after irradiation in seminiferous tubules at stages II-III and IV-V. IL-1 bioactivity was increased significantly at 6 and 25 days after irradiation at stages II-VI during repopulation of spermatogonia. At 2, 6 and 25 days after irradiation at stages VIIa-c a significant increase in IL-1 bioactivity was observed that correlated with repair synthesis of DNA. Increased IL-1 bioactivity was also observed at stages IX-XII at 6 days post-irradiation. These observations support the concept that IL-1 is a spermatogonial growth factor which might also stimulate repair synthesis of DNA. PMID- 8514430 TI - Vitamin E levels in seminal plasma can be elevated by oral administration of vitamin E in infertile men. PMID- 8514431 TI - Current challenges in impotence research. PMID- 8514432 TI - Analysis of spermatozoa from the proximal vas deferens of fertile men. AB - Fluids from the left and right proximal vas deferens were collected from 105 normal fertile men by cannulating the vas deferens during vasectomy, and sperm parameters analysed. Sperm motility (73.1 +/- 13.3%), normal sperm morphology (75.2 +/- 11.1%), sperm viability (72.7 +/- 18.8%) and the hypo-osmotic swelling test (73.3 +/- 19.2%) were in the normal range, compared with that of ejaculated spermatozoa. However, sperm concentration in the proximal vas deferens (6274.6 +/ 5103.8 x 10(6) ml-1 was higher than that in semen. Sperm concentration in the right vas deferens was significantly higher (P < 0.05) than that in the left and the percentage of spermatozoa showing abnormal cervical mucus penetration was significantly higher (47%) for the left than for the right (18%). There were no anti-sperm antibodies on the surface of spermatozoa from the vas deferens as determined by the sperm cervical mucus contact test and immunobead test. These parameters of spermatozoa from the proximal vas may reflect those of spermatozoa from the human cauda epididymis. PMID- 8514433 TI - Modification of human sperm function by human follicular fluid: a review. AB - This review assesses whether human follicular fluid (hFF) is able to modify human sperm function in vitro. Addition of hFF has been found to stimulate the motility of washed human spermatozoa, to increase the percentage of hyperactivated spermatozoa, to induce the acrosome reaction, to attract spermatozoa to the site of fertilization and to facilitate penetration of the oocyte by spermatozoa. It is possible that hFF could provide a favourable environment around the oocyte for fertilization by spermatozoa. Inclusion of hFF in gamete transfer medium may also improve the success rate of assisted reproduction technology. Purification of individual components in hFF which modify different aspects of sperm function awaits further investigation. PMID- 8514434 TI - Use of human zonae from cryopreserved oocytes in a test to assess the binding capacity of human spermatozoa. AB - Aged unfertilized oocytes from an assisted conception programme were cryopreserved and then utilized after thawing in a zona-binding assay. Oocytes frozen using dimethyl sulphoxide (DMSO) showed poor survival post-thaw (2/40, 5%) compared to those frozen with propanediol (PROH) (63/134, 47%). When the zonae were exposed to spermatozoa from fertile donors, those frozen with DMSO showed a significantly higher number of bound spermatozoa than did those frozen with PROH (P < 0.002). In both groups, oocytes which failed to survive the freeze-thaw processes had greater numbers of bound spermatozoa than did those which survived (P < 0.05). Oocytes from cases of failed fertilization showed no difference in their rate of sperm binding compared with oocytes from cases in which some fertilization had occurred. Zonae frozen in PROH but which were from oocytes which were not viable after thawing were used to assess the binding of spermatozoa from men who had failed previously to fertilize their partner's oocytes in vitro and spermatozoa from men with poor quality semen and who had elected for treatment by micro-injection sperm transfer. The number of spermatozoa bound to zonae was reduced significantly in both groups compared to a fertile donor. PMID- 8514435 TI - Identification of auditory brainstem responses. AB - Auditory brainstem evoked responses are routinely used in audiology and otoneurology. An automatic method can be used to roughly classify the responses into probably normal, probably abnormal, and uncertain cases. Interpretation of the auditory brainstem response is a multistage process. Essential tasks are to detect individual peaks in the waveform and to choose representatives examples as medically interesting Jewett components. Our method is based on the comparison of detected peaks and normal values by means of an evaluation function, choosing representatives so that the values of this function will be maximized. We have studied the effects of some evaluation functions on the ability to correctly classify an evoked response. It turns out that the choice of an appropriate evaluation function is crucial in some problematic cases. PMID- 8514436 TI - Visual modelling. AB - The first purpose of this paper is to present a neural net model of the visual cortex of higher vertebrates based on the electrophysiological properties of the ganglion cells. This model takes Hebb's law [1] as the physiological learning rule for synaptic modification. The model consists of 85 x 85 neurons forming a layer similar to the cortex. The neurones are massively connected via weights that are typically adapted. We simulate several input patterns and show that the model reproduces the pattern recognition, contours pictures and moving perception. PMID- 8514438 TI - Formulas predicting survival in patients with heart transplantation. AB - Kirklin et al. (J Heart Transpl. 7 (1988) 331-336) reported survival data in 132 patients who underwent heart transplantation. Survival was evaluated by using the product-limit method of Kaplan-Meier and maximum likelihood method. In addition, the effect of pulmonary vascular resistance on survival was estimated by using multivariate analysis. A microcomputer program in BASIC for predicting the survival probability after transplantation in patients with heart transplantation is designed. The formula used in this program is derived from the survival data reported by Kirklin et al. (J Heart Transpl. 7 (1988) 331-336). A mathematical model of the 'probacent'-probability equation and a computer program previously published by the author are employed in this study. Analysis of the computer assisted predicted values and the data reported by Kirklin et al. (J Heart Transpl. 7 (1988) 331-336) indicates that the program is accurate and reliable with a complete agreement in expressing survival probability as a function of time after heart transplantation. The computer-assisted predictive formula can determine the relationship between the time and the survival probability and may be of value for prognostic evaluation of patients. The computer-assisted mathematical model of the 'probacent'-probability equation may be proposed as a general approximation method to make useful predictions of probable outcomes in various biomedical phenomena. PMID- 8514437 TI - Two-level classification schemes in medical diagnostics. AB - A two-level classifier for medical applications is considered. Such classifiers are expected to yield a more precise result than classical one-level classifiers. The underlying idea for two-level classification is supported by the routine practice of physicians to confirm the diagnosis by several data-driven inferences. An overview of the types of the two-level classifiers is presented. The competitive two-level classifier is emphasized. Three examples with real clinical data are presented from the fields of cardiology, aviation medicine, and neonatology. PMID- 8514439 TI - Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo techniques. I. Illness attack rates. AB - This is the first of a series of papers concerning sensitivity analyses of stochastic micropopulation models. A model of epidemic spread of viral infection is used in this series to illustrate the principles and performance of the sensitivity analysis system. For these studies the analysis system now known as SENSEN was redesigned and extended to use the principles and modules of the SUMMERS simulation shell. The latter was used in the implementation of the epidemic model as well as a number of others. The SENSEN system can be used with any of these. The advantages of sensitivity analysis for stochastic micropopulation models are discussed. Its general form and operation are illustrated by a comparison of illness attack rates with infection attack rates. PMID- 8514440 TI - Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo techniques. II. Durations and peaks. AB - This is the second of a series of papers concerning sensitivity analyses of stochastic micropopulation models. A model of epidemic spread of viral infection is used in the series to illustrate the principles and performance of the sensitivity analysis system. For these studies the analysis system now known as SENSEN was redesigned; it can be used with any specialization of the SUMMERS simulation shell. Previous applications of SENSEN and its predecessors studied the sensitivity simultaneously to at most six input parameters. The applicability of SENSEN when twelve input parameters are selected is illustrated by sensitivity analyses of epidemic durations. A time-related output, day of the epidemic at which the peak number of cases are present, is also studied. PMID- 8514441 TI - A three compartment open model with two time lags. AB - The present study deals with the identification of exchange parameters involved in a three-compartment open model with two time lags in which elimination occurs from the central compartment. Two different optimization methods have been used which involve the reduction of different unknowns to a single variable theta, with the help of Archimedes Spiral. Thus, the solution requires the global minimum of a functional of single variable theta. Results are compared with those obtained by the generalized least square method. PMID- 8514442 TI - Linking environmental and health care databases: assessing the health effects of environmental pollutants. AB - The assessment of pollutant effects on health status requires the mergence and analysis of two different databases: pollution measurements and health care information. This paper compares two subsets of these data: Ohio Environmental Protection Agency data on ambient air pollutants and Ohio Medicare data on respiratory diseases. Small area analysis was performed to assess statewide variations in hospital admission rates for respiratory diseases. The ambient air pollutant levels for each small area were compared to the variations in respiratory disease rates. Five groups of diseases correlated with pollutant levels. In addition, pollutant levels were significantly associated with medical complications. This study demonstrates the feasibility and benefit of linking environmental and health care databases and suggests the need for a more comprehensive, automated analysis of more pollutants and diseases. PMID- 8514443 TI - Sleep staging with movement-related signals. AB - Body movement related signals (i.e., activity due to postural changes and the ballistocardiac effort) were recorded from six normal volunteers using the static charge-sensitive bed (SCSB). Visual sleep staging was performed on the basis of simultaneously recorded EEG, EMG and EOG signals. A statistical classification technique was used to determine if reliable sleep staging could be performed using only the SCSB signal. A classification rate of between 52% and 75% was obtained for sleep staging in the five conventional sleep stages and the awake state. These rates improved from 78% to 89% for classification between awake, REM and non-REM sleep and from 86% to 98% for awake versus asleep classification. PMID- 8514444 TI - In primary human breast carcinomas mutations in exons 5 and 6 of the p53 gene are associated with a high S-phase index. AB - A series of 121 human breast tumors was screened for point mutations in exons 5 through 8 of the p53 gene, by SSCP analysis. On the same tumor samples, the S phase index (SPI) was determined by the incorporation of BUdR in fresh tissue. p53 mutations were observed in 29% of the cases. The frequency of point mutations for the individual exons was: exon 5, 10.0%; exon 6, 9.9%; exon 7, 7.1% and exon 8, 5.5%. Two mutations detected by SSCP were confirmed by sequencing the p53 cDNA. The presence of a p53 mutation, irrespective of its location, correlates (p = 0.003) with a high SPI. This association appears to primarily reflect mutations in exon 5 (p = 0.0002) and exon 6 (p = 0.05), since mutations in exons 7 and 8 failed to show any association. These results indicate that mutations in the p53 gene identify highly proliferating tumors, and that the position of the p53 mutation may have different effects upon the proliferative activity of tumor cells in vivo. PMID- 8514445 TI - Increased risk of nasopharyngeal carcinoma among males of French origin born in Maghreb (north Africa). AB - A study on the incidence of nasopharyngeal carcinoma (NPC) has been performed in the Provence-Alpes-Cote d'Azur (PACA) region, South of France, where Maghrebian migrants represent 10% of the population. During the years 1986-1990, 76 cases of NPC were diagnosed, of which 44 were French by birth, 25 were Maghrebian migrants and 7 were other migrants. We found that 36% of the French patients were either born in endemic areas or had lived there for more than 15 years. Standardized annual incidence rates of NPC among Maghrebian migrants remained close to those observed in North Africa, while, standardized annual incidence rates for French by birth in the PACA region were similar to those observed in cancer registries in other regions of France and countries of low incidence. However, for males of French origin born in Maghrebian countries, the incidence of NPC (all cases being of undifferentiated type) was 5.7 times higher than that of males of French origin born in France (p = 0.00001). These results favor a critical role of environmental factors in the risk of NPC. PMID- 8514446 TI - trk and ret proto-oncogene expression in human neuroblastoma specimens: high frequency of trk expression in non-advanced stages. AB - Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF. PMID- 8514447 TI - Sulfated proteoglycans in the extracellular matrix of human breast tissues with infiltrating carcinoma. AB - The size, content and distribution of sulfated proteoglycans, constituents of the extracellular matrix, were investigated in non-neoplastic human breast tissues and in tissues with infiltrating carcinoma. Sulfated proteoglycans were identified as cuprolinic-blue-positive elements on electron microscopy preparations by the method of the critical electrolyte concentration. Morphometric data indicated that the numerical density of PG per surface area (NA) in normal tissues was about 2 to 7 times higher respectively in dense or loose connective zone then that found in the corresponding zones of malignant tissues. By referring to the unit volume of tissue, the overall PG content (Nv) was found to be increased about 5 fold in nonneoplastic tissues. However, in tissues with carcinoma the average length of sulfated proteoglycans was about twice as long in dense and loose connective layers than in the corresponding connective zones of non-neoplastic breast tissues. Our findings provide evidence of profound structural alterations of non-collagenous constituents in the extracellular matrix of human mammary tissues concerned with infiltrating carcinoma. PMID- 8514448 TI - Effect of organized screening on the risk of cervical cancer. Evaluation of screening activity in Iceland, 1964-1991. AB - The Icelandic Cancer Society launched a screening programme for cervical cancer in June 1964. The aim was to lower the incidence and mortality rates by screening the age group 25-69 at 2- to 3-year intervals. This report analyses the trends in invasive and pre-invasive disease and the distribution of stage and histology, and also evaluates the attendance, the target age group and the screening interval. Before screening, the incidence and mortality rates were on the increase but both have since fallen significantly. Screening greatly affected the rate of microinvasive and stage > or = II squamous-cell carcinomas but not the rate of adeno- and adenosquamous carcinoma. The mean age at detection of invasive cancer has decreased significantly and cancer has become practically non-existent among correctly screened subjects over the age of 69. Among younger women the rates of moderate and severe pre-invasive lesions at first visit increased significantly after 1980. The rate of these lesions was fairly consistently high only 1 year after the first normal visit. It is concluded that organized screening, co-ordinated with spontaneous activity, is effective in reducing the risk of cervical cancer. Regular high attendance and strict follow-up of abnormal cases is a prerequisite for good screening results. Screening should preferably start at about the age of 20 and extend to 60-69 years of age, depending on the number of negative smears by that age. Screening can safely start with a screening interval of 2 to 3 years, but this interval can probably be extended to 4 or 5 years at older ages. PMID- 8514449 TI - Expression of the target antigen for cytotoxic T lymphocytes on adult T-cell leukemia cells. AB - Adult T-cell-leukemia (ATL) cells were examined for susceptibility to human T cell-leukemia virus type I (HTLV-I) tax-specific cytotoxic T lymphocytes (CTL) derived from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). These CTL efficiently killed HLA-matched leukemia cells of an ATL patient after overnight incubation. However, ATL cells immediately after isolation from the peripheral blood were only marginally susceptible to the CTL. This is not due to inappropriate expression of major-histocompatibility-complex (MHC)-class-I antigen on the leukemia cells. Addition of synthetic peptide, corresponding to the CTL epitope, to the assay enabled the CTL to kill the fresh ATL cells. Scarcity of HTLV-I antigens in the fresh ATL cells and induction of these antigens by in vitro incubation were demonstrated both on the cell surface and in the cytoplasm. Lectin stimulation augmented synthesis of HTLV-I antigens, but was not essential for the induction. The presence in the culture of human plasma containing a high titer of antibodies to HTLV-I did not affect the induction of HTLV-I expression in the ATL cells. Furthermore, significantly lower levels of HTLV-I tax mRNA were present in the fresh ATL cells than in the cultured ATL cells, whereas the levels of HTLV-I proviral tax gene did not differ among these cells. This suppression of HTLV-I transcription in fresh ATL cells accounts for resistance to the CTL, and could be a reason for the persistence of HTLV-I infection in vivo. PMID- 8514450 TI - X-ray-induced chromatid damage in relation to DNA repair and cancer incidence in family members. AB - The cytogenetic response to G2-phase X-irradiation was examined in phytohemagglutinin-stimulated peripheral-blood lymphocytes from 69 individuals, a few of whom were cancer patients. The cancer patients had not received radiation or chemotherapy. The responses of cells arrested by Colcemid 30 to 90 min after X irradiation (58R) could be divided into 2 distinct categories: 51 individuals had aberration frequencies typical of normal individuals in previous studies, while 18 others had a 2- to 3-fold higher frequency of chromatid breaks and gaps. Because chromatid breaks and gaps result from unrepaired DNA strand breaks, the first category may represent an efficient DNA repair phenotype, while the second may represent a deficient repair phenotype. The individuals with the deficient G2 response reported having first- and second-degree relatives with a 3.6- and 2.2 fold higher mean frequency of cancer, respectively. The present results, together with those from earlier studies of families with a genetic disorder predisposing to cancer, suggest that this deficient cytogenetic response to G2 phase X irradiation is associated with a high risk of cancer. PMID- 8514451 TI - Estimates of the worldwide incidence of eighteen major cancers in 1985. AB - The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer--by far the most important cancer of women (19.1% of the total) -is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major preventable causes of cancer today. PMID- 8514452 TI - Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers. AB - The expression of MMP-7 (pump-1) gene was examined in 10 cases of colorectal cancer by utilizing RT-PCR. In 9 out of 10 cases, MMP-7 mRNA was detected in cancerous tissue, whereas none was detected in adjacent normal colon tissue. However, this message was detected in only 1 out of 6 colon-cancer cell lines. In colonic mucosa from 3 patients with ulcerative colitis it was not detected. The expression of MMP-2 (72-kDa type-IV collagenase) mRNA was also investigated in the same tissue samples, and was detected in all samples, including cancerous and non-cancerous tissue. Our data suggest that MMP-7 is expressed in a tumor associated manner in colorectal cancers and may play a role in tumor progression. PMID- 8514453 TI - Prediction of response to endocrine therapy in breast cancer using immunocytochemical assays for pS2, oestrogen receptor and progesterone receptor. AB - Histological sections obtained from 70 patients with breast cancer, all of whom had received endocrine therapy for metastatic or locally advanced disease, were assessed for specific immunocytochemical staining of oestrogen receptor and the oestrogen-induced protein pS2. There was also sufficient material from 25 patients for an assessment of progesterone receptor by immunocytochemistry. We found that, when using a "cut-off" point of 50% for ER and PR, and of 25% for pS2, ER was positive in 22/29 responders and in 12/41 non-responders, and thus was significantly associated with response to endocrine therapy. Similarly, in those subjects in whom PR was measured, PR was positive in 5/14 responders and negative in all 11 non-responders, again being significantly correlated with response. However, pS2 did not relate to response, being only positive in 10/29 responders and negative in 26/41 non-responders. The different response categories varied in their "percentage of positivity" as determined by the 2 tests. Thus, for ER and pS2 we observed: complete response--71% for ER compared with 14% for pS2; partial response--77% compared with 41%; stable disease--36% compared with 64%; and progressive disease--27% compared with 27%. We conclude that at the present time ER appears to be the most reliable indicator for predicting response to endocrine therapy in patients with breast cancer. PMID- 8514454 TI - Ectopic production of heparin-binding growth factors and receptors for basic fibroblast growth factor by rat mammary epithelial cell lines derived from malignant metastatic tumours. AB - A rat mammary (Rama) epithelial cell line, Rama 704, derived from normal rat mammary gland does not possess any detectable cell-surface receptors for basic fibroblast growth factor (bFGF), produces a barely detectable level of bFGF mRNA and does not contain detectable levels of bFGF-like activity. Similar results have been obtained with the Rama 37 epithelial cells derived from benign tumours. However, 4 independently isolated epithelial cell lines derived from malignant rat mammary tumours and their metastases possess receptors for bFGF and contain between 2 ng and 9 ng heparin-binding, growth-stimulatory activity per 10(6) cells. The weakly metastatic Rama 600 cells possess high- and low-affinity receptors for bFGF, (KD 20 pM and 8 nM, respectively), while the moderately metastatic Rama 800 cells possess only high-affinity receptors (KD 40 pM). The moderately metastatic C18PLN and 267LU cells, derived from metastases arising from benign Rama 37 cells which had been transfected with DNA from the malignant Rama 800 cells, also possess only high-affinity receptors (KD 36 pM and 80 pM, respectively). Our results show that within the Rama system there is a correlation between the appearance of heparin-binding growth factors and of high affinity but not low-affinity receptors for bFGF with the malignant phenotype. PMID- 8514455 TI - Lysis of human pancreatic adenocarcinoma cells by autologous HLA-class I restricted cytolytic T-lymphocyte (CTL) clones. AB - From the primary site of a pancreatic adenocarcinoma (patient BE) a permanent cell line (MZ-PC-2) was established in tissue culture. In the course of mixed lymphocyte-tumor-cell cultures (MLTC) with autologous blood-derived lymphocytes, we isolated CTL clones that lysed autologous tumor cells but not autologous EBV transformed B cells (EBV-B) and not K562. Pre-treatment of MZ-PC-2 cells with IFN gamma was required to obtain significant lysis in 4-hr cytotoxicity assays. IFN gamma was superior to IFN-alpha in that respect. Among MLTC responder lymphocytes, tumor-reactive CTL proliferated more strongly in response to MZ-PC-2 cells treated with IFN-gamma than to untreated tumor cells. Three CTL clones derived from MLTC were chosen for further analysis. They were CD3+, CD8+, TCR alpha/beta+ and behaved identically in all functional aspects tested. They all expressed the same TCR-beta chain, indicating that they descended from a common precursor lymphocyte and were directed against the same antigen. According to antibody-inhibition experiments, BE-CTL recognized their targets via an HLA-B molecule carrying the Bw6 supertypic determinant. Irrespective of pre-incubation with IFN-gamma, low levels of tumor-cell lysis, or none, were seen when MZ-PC-2 cells were kept in medium supplemented with autologous serum or serum pooled from healthy volunteers instead of FCS. Lysability was restored when TNF-alpha was added to human serum. Serum-free medium was found to enhance the susceptibility of MZ-PC-2 cells to lysis by autologous CTL. PMID- 8514456 TI - The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma. AB - The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro. PMID- 8514457 TI - The effect of hypoxia on acquired drug resistance and response to epidermal growth factor in Chinese hamster lung fibroblasts and human breast-cancer cells in vitro. AB - Prolonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following reaeration for 24 hr. A change in P-glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast cancer cell lines. MDA-468 and MCF-7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic-stress induced drug resistance is not generalized. PMID- 8514458 TI - Role of plasminogen activators, metalloproteinases and the tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary-gland adenocarcinoma cells. AB - An in vitro system has been established in which conversion from non metastasizing to metastasizing adenocarcinoma cells can be induced, and subsequently subjected to analysis of the expression of proteases and tissue inhibitor of metalloproteinases-1 (TIMP-1). A human salivary-gland adenocarcinoma cell clone HSGc, with no metastatic ability, was exposed to N-methyl-N nitrosourea (MNU). Following exposure to MNU, cells with altered morphology were cloned. Upon s.c. inoculation into nude mice, MNU-treated HSGc clones formed metastatic foci in various organs, and then 5 metastasizing clones were isolated. Evaluation of expression of tissue-type plasminogen activator (tPA), urokinase type plasminogen activator (uPA), metalloproteinases and TIMP-1 was performed by means of enzyme immunoassay, zymogram, or immunoblot. MNU-treated HSGc and metastasizing clones were found to secrete high levels of tPA, while HSGc produced undetectable levels of this enzyme. Expression of uPA was not observed in any of the cell clones. When the secretion of gelatinolytic enzymes was examined, metastasizing clones produced higher levels of 57- and 32-kDa, but not of 92- or 72-kDa gelatinases, as compared to HSGc cells. Although TIMP-1 was detected in all cell clones, metastasizing clones secreted less TIMP-1 than HSGc cells; in addition, one metastasizing clone produced TIMP-1 with a molecular weight distinct from that of 28-kDa TIMP-1. Our results suggest that the acquisition of metastatic ability by human salivary-gland tumor cells is closely associated with increased secretion of several metalloproteinases as well as decreased or altered TIMP-1 expression. PMID- 8514459 TI - Eradication of spontaneous and experimental adenocarcinoma metastases with chronic indomethacin and intermittent IL-2 therapy. AB - We had earlier shown that tumor-bearing results in an inactivation of IL-2 dependent effector cells by host macrophage-derived PGE2, and that chronic indomethacin therapy (CIT) aimed at blocking prostaglandin synthesis, combined with multiple rounds of IL-2, can cure experimental metastases of a variety of tumors in mice. We have now tested the efficacy of this therapy on spontaneous as well as experimental metastasis of C3-L5 mammary adenocarcinoma in C3H/HeJ mice. Mice transplanted s.c. with C3-L5 cells (and showing visible spontaneous lung metastases between days 7 and 10) were given CIT starting on day 15, plus 2 5-day rounds of IL-2 or IL-2 alone. Mice injected i.v. with 10(4) C3-L5 cells (and showing lung micrometastases on day 5) were placed on CIT on day 5 and given 3 5 day rounds of IL-2 or treated with IL-2 alone. Control mice received vehicles alone. Results revealed that combined CIT + IL-2 therapy in the spontaneous metastasis model caused a regression of primary tumors, a marked reduction in lung metastases scored on days 25-35 and a marked prolongation of host survival (79% cured). Survivors rechallenged with 10(4) tumor cells i.v. on day 210 resisted tumor growth. In the experimental metastasis model, this therapy also markedly reduced lung metastases and prolonged animal survival (50% cured). In both models, the combination therapy led to the presence of highly active tumoricidal (for C3-L5 and YAC-1 lymphoma targets) lymphocytes with AGM-1+, Lyt-2 and Thy-1 +/- phenotype and macrophages in the spleen and the lungs, and ADCC promoting activity in the serum. CIT + IL-2 therapy can thus effectively eradicate spontaneous and experimental mammary adenocarcinoma metastasis in mice. It activates natural effector cells in situ, generates ADCC-promoting activity in the serum and results in resistance to tumor take in this moderately immunogenic tumor model. PMID- 8514460 TI - Mutation and expression of the p53 gene in malignant melanoma cell lines. AB - Three monoclonal antibodies (MAbs) against p53 protein (PAb 24o, DO-I and PAb1801) were used to define the immunophenotype of 13 melanoma cell lines. Immunoreactions could be detected in 12 out of 13 cell lines by using the indirect immunofluorescence technique. In 7 of these the majority of cells displayed cytoplasmic staining whereas positive nuclei were detected in only a few cells. Two cell lines had predominantly nuclear reactivity, while the remaining 3 cell lines showed signals in both locations. Despite identical nuclear staining patterns, the 3 MAbs produced qualitatively distinct cytoplasmic immunoreactions. PAb240 and DO-1, which showed similar staining frequencies, appeared more sensitive in the detection of p53 protein than did PAb1801. Immunoprecipitations of lysates from each of the cell lines, with MAbs DO-1 and 1801 (which bind to both wild-type and mutant p53 species) detected 53-kDa proteins, whereas PAb240 (which recognizes the mutant conformation of the protein in this type of assay) detected 53-kDa proteins in only 4 cell lines. Nucleotide sequencing of exons 5 to 9 of TP53 in these latter cell lines showed that each has homozygous point mutations in the locus, whereas in the others no TP53 alterations were found. Three of the 4 mutations were C-to-T transversions, alterations possibly caused by damage from UV-light. Our findings indicate that immunostaining with p53 antibodies, although common in malignant melanoma, results from the presence of mutant p53 protein in about 30% of the cases tested. Neither immunostaining with PAb240 nor the patterns of intracellular distributions of the signals are sufficient to detect TP53 mutations. PMID- 8514461 TI - Neuroblastoma incidence in south-east France. PMID- 8514462 TI - Altered serotonergic activity in women with dysphoric premenstrual syndromes. AB - OBJECTIVE: Dysphoric Premenstrual Syndromes (PMS) are quite prevalent and in some women they are severe enough to warrant treatment. Their pathophysiology is still unknown, despite increased interest and research. Here we review the possible role of serotonin in the multidimensional interactive pathophysiology of PMS. METHOD: Over 170 articles are reviewed. An extensive library search has been conducted and articles are included because of their relevance to: 1) the phenomenology of PMS; 2) the putative association of serotonergic (5-HT) activity with syndromes that occur premenstrually; 3) changes in 5-HT activity along the menstrual cycle, especially the late luteal phase; 4) influence of gonadal hormones on serotonergic functions; 5) endocrine strategies for assessment of 5 HT abnormalities; and 6) treatment studies of PMS with serotonergic agonists. RESULTS AND CONCLUSIONS: The data presented here suggest that post-synaptic serotonergic responsivity might be altered during the late-luteal-premenstrual phase of the menstrual cycle. Some serotonergic functions of women with PMS might be altered during the entire cycle and be associated with a vulnerability trait. It is hypothesized that gonadal hormones might cause changes in levels of activity of 5-HT systems as part of a multidimensional interactive system. Strategies to evaluate 5-HT activities in the context of the menstrual cycle are discussed--leading to the conclusion that the most promising approach is active stimulation with specific post-synaptic serotonin agonists. Treatment outcome studies of some imperfect compounds that are currently applied as a symptomatic treatment of PMS support the notion that 5-HT is involved in the pathophysiology of these syndromes. PMID- 8514463 TI - Clinical trials of primary care treatments for major depression: issues in design, recruitment and treatment. AB - The objective of this article is to consider whether randomized clinical trials (RCTs) are able to determine the validity of transferring treatments for major depression from the psychiatric to the primary care sector. This clinical issue is of growing concern in the United States since both governmental and professional bodies are establishing guidelines for the treatment of medical patients with the affective disorder. The article's method involves analysis of how the competing aims of rigorous scientific methodology (internal validity) and generalization of study findings (external validity) are best balanced within the RCT. Experiences in recruiting medical patients with major depression and providing pharmacologic, psychotherapeutic, and usual care interventions compatible with the sociotechnical characteristics of ambulatory medical centers are described to illustrate the complexities of investigating transferability of treatments for major depression with RCT methodology. PMID- 8514464 TI - Psychiatric assessment of patients with life-threatening cardiac arrhythmias. AB - OBJECTIVE: This article describes the development of a protocol specifically designed for the psychiatric assessment of patients with life-threatening ventricular arrhythmias. METHOD: Psychiatric assessment occurs in the context of a team approach in which the cardiologist has a pivotal role. Initial findings and one-year follow-up data on the first twenty-five patients evaluated psychiatrically are presented. RESULTS: Findings tend to confirm that psychiatric complaints are common on initial assessment and suggest that patients with life threatening ventricular arrhythmias who do not use the psychological mechanism of denial and volunteer psychological complaints may constitute a subgroup of patients who would be more amenable to psychiatric intervention compared to those denying psychological complaints at initial psychiatric interview. CONCLUSION: Psychiatrists and associated professionals should become more involved with patients with life-threatening cardiac arrhythmias. PMID- 8514465 TI - The lithium toxic patient in the medical hospital: diagnostic and management dilemmas. AB - OBJECTIVE: Patients with lithium toxicity can pose difficulties in diagnosis and management in the general hospital setting. The authors examined patients who were referred to the Psychiatric Consultation-Liaison Service with suspicion of lithium overdose to delineate and characterize medical and psychiatric risk factors for toxicity and to follow the course and resolution of their toxicity. METHOD: The authors reviewed the charts of patients with lithium levels > 1.5 mEq/L who were admitted consecutively to a general hospital over an 18-month period. RESULTS: Of twelve patients, eight were found to have developed lithium toxicity due to incidental and iatrogenic factors. These patients presented with a variety of confusing signs and symptoms. Hypothyroidism and coexisting organic illness contributed to the lack of clarity in their clinical picture. CONCLUSION: The widening scope of indication for lithium therapy leads to increased risk of toxic reactions which challenge the diagnostic skills of the consulting psychiatrist in a general hospital setting. PMID- 8514466 TI - Biogenic, psychogenic, and sociogenic models of adjustment to chronic pain: an exploratory study. AB - OBJECTIVE: Based upon three models of etiology and adjustment in CLBP, predictions were made about the variables that were expected to differentiate organic and nonorganic patients, including: psychological distress (anxiety, depression, stress, alienation), pain condition and treatment, and general health. METHOD: Patients from a medical school orthopedic clinic with an organic (N = 58) or a nonorganic (N = 33) diagnosis for chronic low back pain (CLBP) were compared on medical, psychological and sociodemographic variables. RESULTS: Nonorganic patients exhibited greater emotional distress, contrary to the biogenic model, and nonorganic patients did not exhibit more somatic complaints, contrary to the psychogenic model. Both patterns were consistent with the sociogenic model; nonorganic patients were more distressed, but not because of a greater tendency to somatize. Moreover, modeling was not supported as an explanation of the pain and distress among these patients. CONCLUSIONS: Social anomie may explain why patients without a medically diagnosable cause for their pain are more psychologically distressed. PMID- 8514467 TI - Update on factitious disorders. AB - OBJECTIVE: Since factitious disorders entered the official psychiatric nomenclature in DSM-III and DSM-III-R, there has been a proliferation of reports and commentary about this unusual disorder. We present an update of the recent literature. METHOD: The psychiatric and medical literature was searched. Clinical reports and critical/theoretical papers were reviewed; eighty-five are summarized here. RESULTS: Available data is descriptive and anecdotal. Reports focus on the following four topics, which are discussed here: 1) diagnostic issues, 2) the newly proposed DSM-IV category of factitious disorder by proxy, 3) epidemiology and course, 4) new developments in treatment and management. CONCLUSIONS: Factitious disorders are uncommon but serious illnesses that present diagnostic and management dilemmas. Deriving systematic information about these illnesses is a major challenge. PMID- 8514468 TI - Spontaneous large intra-abdominal wall haematoma as a rare complication in a maintenance haemodialysis patient. AB - The incidence of spontaneous bleeding in various parts of the body has been reported to be high in patients receiving maintenance haemodialysis. We present a case of spontaneous large haematoma of the intra-abdominal wall which developed in a 71-year-old Japanese man with 9 years' maintenance haemodialysis. Due to the clinical symptoms and signs, ileus was suspected and an emergency operation was performed. In maintenance haemodialysis the possibility of spontaneous bleeding should always be considered whenever unexplained and unexpected symptoms and signs are apparent. PMID- 8514469 TI - Haemodialysis treatment in phenobarbital intoxication in infancy. AB - Haemodialysis treatment was performed in a comatose infant who was 9 months old. At the beginning of haemodialysis plasma phenobarbital concentration was found to be 120 micrograms/ml. The constant low flux haemodialysis lowered the plasma phenobarbital concentration to 64.2 micrograms/ml and haemodialysis was terminated at the end of six hours. The patient recovered fully after haemodialysis session. This case indicates that haemodialysis is an effective and successful treatment method in phenobarbital intoxication also in infancy. PMID- 8514470 TI - Are we overstressing water quality in urinary stone disease? AB - A door to door survey of 38,805 persons from urban (9527) and rural (nontribal- 19,716; tribal--9562) areas was carried out from 59 localities of Udaipur region to find out the prevalence of urinary stone disease. Simultaneously 118 water samples were also collected. The three sources of drinking water in these localities were tap, handpump and well and the prevalence of urinary stone disease in relation with the source of drinking water was 548.3, 303.4 and 189.9/1,00,000 population, respectively. All the samples were analysed for total hardness, Ca, Mg, Na, K, iP, SiO3, SO4, Cl, F, Cu, Zn and Mn. The tap water was softest with highest prevalence. The chi-square test revealed that prevalence was unassociated with any of these constituents. We feel that overstress should not be given to quality of drinking water in the management of stone disease. PMID- 8514471 TI - The value of ultrasonography as a screening procedure of the neonatal urinary tract: a survey of 1021 infants. AB - In 1021 children, aged several hours to 21 days, sonographic investigations of kidneys and bladders were performed. 1001 children without any urinary tract abnormality were divided into 7 body weight-dependent groups. The kidney volume was correlated to somatometric data including body weight and body length, breadth of thorax, and head circumference. Regression line for the dependence of renal volume on body weight was calculated. The remaining 20 children with urinary tract abnormalities were described separately. During ultrasonic screening examination, bladder or renal disorders found in those 20 children were as follows: mild hydronephrosis in 6 cases, and severe hydronephrosis in 4 cases; of the latter 1 case was caused by ectopic ureterocele, 1 by simple ureterocele, 1 by obstruction of the distal ureter (primary megaureter) and 1 by vesicoureteral bilateral reflux. In 2 cases unilateral multicystic kidneys were found, 2 infants had an ultrasound pattern with hyperechoic medulla, in 4 cases unilateral non-obstructed renal duplication was suspected, and in 2 cases only a single kidney was found. PMID- 8514472 TI - Percutaneous injection sclerotherapy with minocycline hydrochloride for simple renal cysts. AB - Minocycline hydrochloride as a sclerosant for the treatment of simple renal cysts was evaluated. Cyst puncture was performed, and minocycline hydrochloride solution for intravenous administration was injected after aspiration. Of 154 cysts evaluated by ultrasound after 3 months or more, 69 were no longer demonstrable, 49 showed 50% or greater reduction in the maximum cyst diameter, and only 8 were unchanged or slightly increased in size. In contrast, only 1 of 20 cysts aspirated without minocycline hydrochloride injection (controls) showed 50% or greater reduction after 3 months. There was a significant difference in the reduction rates between the minocycline-treated group and control group (p < 0.01). These results suggest that minocycline hydrochloride is an effective sclerosant to treat simple renal cysts. PMID- 8514473 TI - Renal medullary fibroma: a case report and review. AB - A case of renal medullary fibroma in a woman is presented. A CT scan, which was performed for examination of cholelithiasis, incidentally revealed a mass in the left renal pelvis, and retrograde pyelography showed a filling defect in the same site. Left nephrectomy was performed. Histological examination revealed a renal medullary fibroma. The diagnostic and therapeutic dilemmas associated with this condition are discussed. PMID- 8514474 TI - Sarcomatoid renal cell carcinoma. An immunohistochemical and ultrastructural study. AB - A case of sarcomatoid renal cell carcinoma is reported with light, immunohistochemical and electron microscopic findings. The tumour consisted of typical clear cells of renal cell carcinoma and spindle cells compatible with malignant fibrous histiocytoma (MFH). Although an epithelial membrane antigen was demonstrated in the clear cells, this was not detected in the MFH-like spindle cells. In contrast, the spindle cells expressed vimentin that was not identified in the clear cells. Electron microscopy reveal epithelial features in the spindle cells. Comparisons were made with previous sarcomatoid renal cell carcinoma in the literature. Thus, ultrastructural study was vital in diagnosis of sarcomatoid renal cell carcinoma. PMID- 8514475 TI - Carcinoma of the urachus. A case report and review of the literature. AB - A 63-year-old man presented with haematuria and suprapubic pain. After transurethral resection of the prostate a tumour was seen in the bladder dome at cystoscopy. Biopsy revealed an adenocarcinoma. Based on intraoperative and histological examination of the partial cystectomy specimen, the tumour was judged to be an urachus carcinoma. Four years after diagnosis the patient has no evidence of tumour. While partial cystectomy is the most frequent treatment, a radical total cystectomy is advocated in poorly differentiated tumours. PMID- 8514476 TI - Penile agenesis: an unusual variant. AB - An unusual variant of penile agenesis with a high rectal termination of the urethra is reported. The difficulties faced in the management of this case and the possible aetiology of this rare anomaly are discussed. PMID- 8514477 TI - Self-introduction of foreign bodies into the urethra: a multidisciplinary problem. AB - A 36-year-old man was hospitalized for self-insertion of a metallic body into the urethra. The self-inserted foreign body (SFB) was removed by endoscopic means; psychiatric evaluation of the patient showed a disturbed schizoid personality. After a review of the current literature, including clinical features, diagnostic manoeuvres and methods of treatment of SFB, the authors suggest that a psychiatric evaluation is always recommended in order to discover mental underlying disorders, thus reducing the risk of recurrence. PMID- 8514478 TI - An experimental model for unilateral ischaemic acute renal failure in dog. AB - We determined the recovery of unilateral ischaemic acute renal failure in both ischaemic and non-ischaemic canine kidneys. Split renal clearance studies were repeated for seven weeks after 90 minutes of left renal artery clamping. Clearance of inulin and para-aminohippuric acid in the ischaemic kidneys dropped significantly for 3 weeks. Significant increase of the fractional excretion of sodium in those kidneys was observed at only 1 week after ischaemia. In the contralateral non-ischaemic kidneys, these indices did not change significantly throughout the experiments. This animal model of acute renal failure would be helpful in testing possible preventive measures and therapy for human acute renal failure. PMID- 8514480 TI - Thrombolytic therapy in acute myocardial infarction. Irish Working Party Consensus. PMID- 8514479 TI - Plasma parathyroid hormone and erythropoietin levels in patients with noninflammatory acute renal failure. AB - PTH is incriminated as an uraemic toxin involved in the pathogenesis of anaemia in chronic renal failure. This fact was the background of our present studies performed in 14 patients with noninflammatory acute renal failure (NARF). Plasma levels of erythropoietin (EPO) and parathyroid hormone (PTH) were estimated in the anuric/oliguric (a/o) and polyuric (p) phase of NARF. In the a/o phase plasma EPO levels were predominantly normal, although inappropriately low to the degree of anaemia. In 50% of patients with NARF episodic short-term increases of plasma EPO levels were noticed which were not caused by worsening of anaemia. In the p phase plasma EPO concentrations were in the normal range (17.9 +/- 3.3 mU/ml) in spite of the same degree of anaemia as in the a/o phase. Plasma PTH levels were significantly elevated during the a/o phase (1.14 +/- 0.1 ng/ml), with a tendency to decline in the p phase (0.87 +/- 0.2 ng/ml). No correlation was found between plasma EPO and PTH concentrations. Results presented in this study suggest presence of relative EPO deficiency both during the a/o and p phases of NARF. As plasma PTH levels were not significantly correlated with serum EPO concentrations, its role in the pathogenesis of suppressed EPO levels seems unproven. Results presented in this study suggest deterioration of the physiological feedback between EPO secretion and the magnitude of erythropoiesis in NARF. PMID- 8514481 TI - Whither the rationale for thrombolytic agent administration? A retrospective review of traditional intuitive decision-making using a decision analysis model. AB - Of 50 consecutive patients admitted to Nenagh Hospital coronary care unit 50 per cent did not develop a myocardial infarction. Only 10 patients had definite evidence of infarction on admission. Of the 40 remaining patients, only 15 subsequently developed electrocardiographic and enzymatic confirmation of infarction. Streptokinase was administered to 5 patients who did not infarct, and was not given to 10 patients who did. These decisions to use or withhold thrombolytic therapy were retrospectively reviewed using a computer programme incorporating a decision analysis of the benefits and risks of thrombolysis. The programme examined four scenarios that used different estimates of the chance of death from infarction (pdiMI), and different safety profiles of thrombolytics. The scenario that assumed the worst safety profile and estimated pdiMI from patient age would have recommended thrombolytic treatment to the most with, and to the least without, acute infarction (i.e. 60 per cent of patients with an infarct and 8 per cent without an infarct would have been treated). Depending on the scenario assumed, the traditional intuitive method of decision-making gained from 0.08 and 0.25 quality adjusted life years (QALY's) for the average patient. Had decision analysis been used to guide these decisions these gains would have been enhanced by from 0.21 to 0.28 QALY's per patient, regardless of scenario used. PMID- 8514482 TI - Microalbuminuria does not predict cardiovascular disease in a normal general practice population. AB - Recent studies have suggested that microalbuminuria is relatively common (9.4%) in non-diabetic subjects and that it is an excellent marker for increased cardiovascular risk. In an attempt to assess the prevalence of microalbuminuria in Northern Ireland where there is a high incidence of coronary heart disease, we studied 400 males, age 35-65 years, chosen at random from a Belfast general practice. There was a 73% response rate (n = 273). Sixteen per cent of the population has ischaemic heart disease. Microalbuminuria was defined as an increased urinary albumin excretion rate of 20-200 ug min-1. Thirteen subjects (4.7%) had an albumin excretion rate of 20 ug min-1 or more. After exclusion of subjects with diabetes mellitus or renal diseases, the group with microalbuminuria (n = 8), was compared to those without microalbuminuria (n = 256). There was no significant difference in the incidence of ischaemic heart disease between the two groups, nor did the group with microalbuminuria have a more adverse profile of vascular risk factors, apart from serum triglyceride (1.8 +/- 0.2 v 1.3 +/- 0.0 mmol l-1, p < 0.05) and plasma glucose (5.5 +/- 0.3 v 5.1 +/- 0.3 mmol l-1, p < 0.05) levels. We conclude that in a general practice from an area at high risk of ischaemic heart disease, the prevalence of microalbuminuria was low. Contrary to previous reports, microalbuminuria was not helpful in predicting subjects at risk of ischaemic heart disease. PMID- 8514483 TI - Treatment of rheumatoid hand synovitis with a regional block technique. AB - This study reports a novel technique for treating painful rheumatoid hand synovitis using a regional block technique. Nine patients with symptomatic rheumatoid hand synovitis were treated. Assessments of symptoms, grip strength and synovial swelling were made in each hand before the injection, and at 1 and 4 weeks after the procedure. A sphygmomanometer cuff was inflated, on the side of the patients most symptomatic hand, to 220mmHg and a solution of hydrocortisone sodium succinate 50mgs and lignocaine 10mls 0.5% was injected intravenously. The cuff was deflated slowly after 20 minutes. The injected hand improved symptomatically in 7 patients at 1 week, and further improvement was reported in 6 of these 7 at 1 month. Mean grip strength increased significantly in the injected hand both at 1 week (p = 0.01) and 1 month (p = 0.018). There was no change in the other hand. This technique is safe, reduced hand pain and improved grip strength in these patients with rheumatoid hand synovitis. PMID- 8514484 TI - Transosseous suturing for sleeve fracture of the patella: case report. PMID- 8514485 TI - Case report: xanthogranulomatous pyelonephritis presenting as a cutaneous fistula. PMID- 8514486 TI - Irish Society of Gastroenterology. November 1990. Abstracts. PMID- 8514487 TI - Numbers of infant deaths in Scotland, with special reference to sudden infant death syndrome. AB - There has been an increased interest during 1992 in the numbers of deaths from Sudden Infant Death Syndrome, because of reports of reductions in the numbers in several countries where changes in advice on infant care had been made. Numbers of infant deaths in general and of those due to the syndrome in particular are described and analysed by some of the variables which are provided at the time of registration. The decline in the number of deaths from the syndrome reported recently by the Scottish Cot Death Trust is supported by the full figures for 1991. This decline probably started about the latter part of 1990, well before the official letters giving advice on infant care that had been associated with a decline elsewhere. It was more marked in some areas of Scotland than others. There appears to be a cyclical pattern in the time-series of the numbers of deaths from the syndrome. Further investigation, both of the cyclical movement and of the recent decline in relation to other variables, would be worthwhile. Deaths in the neonatal period from the syndrome and those from other causes have both declined markedly during 1990 and 1991, after several years when the movements in their numbers seemed to be in opposite directions. PMID- 8514488 TI - Asthma in Scotland: epidemiology and clinical management. AB - Asthma in Scotland is briefly reviewed including epidemiology, management and the potential for research, education and audit. Asthma is characterised by variable wheeze and shortness of breath caused by variable narrowing of the bronchial airways secondary to inflammation. Confusion with chronic obstructive airways disease is increasingly common in the elderly and epidemiological studies tend to focus on the age range 5-44 years. Asthma prevalence is critically dependent on the definitions used and exceeds 20% based on questionnaire alone, less if objective measurements of airways obstruction is also used: perhaps 15% in children, 5% in adults in Scotland. Comparisons between studies and countries are therefore potentially hazardous. Routine information sources confirm the high levels of morbidity and use of health services by asthmatic patients. A true increase in the prevalence of asthma in children over the last two decades appears likely. This has been compounded by increased willingness to use the diagnostic label of asthma. Asthma, hayfever and eczema have increased significantly in Aberdeen school children over the last 25 years and asthma symptoms and airways obstruction have increased significantly in South Wales. Similar increases are reported in New Zealand children between 1975 and 1985, the prevalence being significantly higher than in Welsh children using standardised methodology. In Zimbabwe an intriguing strong association has been demonstrated between asthma, urban life style and higher socio economic groups. Most asthma deaths are caused by bronchial narrowing and subsequent asphyxia. Asthma mortality has apparently increased in most industrialised countries but problems of definition remain even when attention is confined to the age span 5-44 years. The epidemic of asthma deaths in mid-60s was undeniable and may have reflected good symptomatic control by bronchodilators, which made doctors and patients neglect the underlying risk of asthma death. A gradual increase in asthma mortality in western countries over the 1970s and 1980s is apparent, including almost 5% annual increase in England and Wales between 1974 and 1984 which then levelled off. This may again reflect excess dependence on bronchodilator treatment and under-usage of steroid treatment. A more dramatic increase in mortality in New Zealand in the early 1980s is likely to have a number of contributory factors. In contrast, the mortality rate in Scotland had been relatively static over the last two decades, although hospital discharge rates have doubled. Emergency asthma self admission schemes developed in Edinburgh are increasing popular and these, along with nebulised bronchodilators in ambulances, may be beneficial.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8514490 TI - From the chief medical officer. PMID- 8514489 TI - Transferring at-risk babies in utero or neonatally. PMID- 8514491 TI - Survey of out-patient satisfaction in a general hospital. AB - This paper describes a brief questionnaire designed to assess patient satisfaction with outpatient services at a general hospital. Its application in the evaluation of services in a hospital in the Highland Area of Scotland is outlined, demonstrating how it can be used to highlight aspects of services that are satisfactory, and those that require improvement. PMID- 8514492 TI - Psychiatric emergency clinic attenders: what can we learn from them? AB - Patients attending the Royal Edinburgh Hospital emergency psychiatric clinic over a four month period were assessed by semi-structured interview. General Practitioner and self-referrals were compared with respect to presenting features and subsequent management. Self-referral was associated with young age, male sex, unemployment, poor social cohesion, problem drinking, a forensic history, and mild levels of psychiatric disorder. Only 10% of self-referrals were considered appropriate psychiatric emergencies, but 69% of General Practitioner referrals. Five per cent of self- and 34% of General Practitioner-referrals were admitted. These findings indicate that if the psychiatric emergency clinic is to be of benefit to those it serves, it must not confine itself simply to assessment of mental disorder, but seek to facilitate crisis resolution. PMID- 8514493 TI - The Scottish Record Linkage System. PMID- 8514494 TI - Human hydatid disease leading to hospital admission in Scotland 1968-1989. AB - An attempt to estimate the impact of hydatid disease upon human health in Scotland between 1968-89 was made by examining Scottish hospital discharge statistics, and death statistics. Because hydatid disease may be asymptomatic, and coding errors are more likely to occur with rare diseases, an assessment was made as to the likelihood of hydatid disease having been responsible for hospital admission. Over the 22 year period a total of 110 hospitalised individuals with a diagnosis of hydatid disease were identified; no deaths were recorded. Inspection of the other diagnoses and operations recorded for each case suggested that hydatid disease was responsible for hospital admission in only 65 individuals (59%). One further individual, who had been admitted to a hospital outside Scotland, was identified from a Western Isles register of cases receiving surgery for hydatid disease. This register was used to assess the completeness of the Scottish hospital statistics; 10/11 Western Isles cases were identified using hospital statistics. Local case registers seem essential for accurate estimates of incidence and prevalence, and to evaluate the need for control programmes. The median age of the 66 individuals considered to have been admitted to hospital because of hydatid disease was 49 years (range 4-85); 38 (58%) were male. A total of 36 cases were managed surgically (55%), and there was a tendency for the use of surgery to increase over the 22 year period. The Health Boards with the highest incidence of clinically apparent infection leading to hospital admission were: Western Isles, Shetland and Highland; with 2.53, 1.23, and 0.21 cases per 100,000 population per year respectively. PMID- 8514495 TI - Pattern and severity of injury sustained by motorcyclists in road traffic accidents in Edinburgh, Scotland. AB - The pattern, severity and circumstances of injury sustained by 52 motorcyclists admitted as the result of a road traffic accident were prospectively documented. Forty-eight of the patients were drivers and four were pillion passengers. Three of the drivers and all of the pillion passengers were female. Injuries to motorcyclists accounted for 0.4% of the total workload of the department during the course of the study, and for 14% of all injuries seen there arising from road traffic accidents. Eighty-nine per cent of the patients were aged less than 25 years and the oldest patient was aged 44 years. Patients under the age of 21 years were injured more severely than those aged 21 years or more. The majority of injuries (67%) involved the limbs with the right arm and leg being injured twice as often as the left arm and leg. Arms and legs were injured with equal frequency. Head and facial injuries comprised only 9% of the total. Two patients were observed not to be wearing helmets at the time of the accident. Patients admitted between midnight and 05.59 hours sustained injuries of greater severity than those admitted between 06.00 and 23.59. Fifty per cent of patients had an Injury Severity Score of less than five, and only four patients had Injury Severity Score of 25 or more. One third of patients were riding motorcycles with an engine size of 750cc or greater. This group of patients was younger than patients riding less powerful motorcycles and also sustained injuries of greater severity. PMID- 8514496 TI - The chief scientist reports ... Evaluation of the Scottish shadow fund-holding project: first results. AB - This paper reports preliminary findings from the action research evaluation of the Scottish shadow fund-holding project. Fifty doctors looking after 84,000 patients in six groups negotiated and managed a paper fund for six months, and then a real fund for six months. First analyses of quantitative data suggest that the numbers of prescriptions written, investigations done and referrals made remained stable over the period of study. The length of time spent at consultations varied apparently independently of holding a fund. Patient satisfaction with actions taken by doctors and their feelings of benefit from consultations were high throughout the study, but a consistent and significant shift from very satisfied to satisfied categories was noted in all practices for most variables surveyed during the course of 1990-91. Analyses to explain this are continuing. Qualitative study identified benefits in terms of a greater understanding of the costs of activities, and new working patterns between hospital, general practice and administrative staff have led to progressive work in contracting for quality of patient care. At the same time, the lack of sophistication of fund setting needs to be addressed; equity issues will become relevant as fund-holding reaches a larger proportion of practices. The pressures on those taking leading roles in administration are high, and this is confirmed by parallel quantitative work. Further information is becoming available on both prescribing and the care of selected 'marker' conditions, and these will be the subject of further reports. PMID- 8514497 TI - Measuring quality of care in psychiatric emergencies: construction and evaluation of a Bayesian index. AB - OBJECTIVE: This study was conducted to determine whether an index for measuring quality of care for psychiatric emergencies is reliable and valid. DATA SOURCES/STUDY SETTING: The study used primary data collected over a 12-month period from two urban hospitals in the Northeast. One had 700 inpatient beds, an inpatient psychiatric unit, and community mental health personnel located in the emergency department. The other had 300 beds but none of the other hospital's features. STUDY DESIGN: The index was developed by a panel of experts in emergency psychiatry using a subjective Bayesian statistical methodology and was evaluated in terms of its ability to: (1) predict a second panel's judgments of quality; (2) predict a specific quality-related patient outcome, i.e., compliance with follow-up recommendations; (3) provide a reliable measurement procedure; and (4) detect variations in patterns of emergency department practices. DATA COLLECTION/EXTRACTION METHODS: Data were collected on 2,231 randomly selected emergency psychiatric patients (psychiatric diagnosis, alcohol abuse, nonverbal patients experiencing a psychiatric emergency, and patients with somatic complaints such as life crisis) treated in the emergency departments of the two hospitals. PRINCIPAL FINDINGS: The index predicted physician judgments of quality, was reliable, exhibited sufficient variation in scores, and was strongly associated with patient compliance. CONCLUSIONS: The study demonstrated that a subjective Bayesian model can be used to develop a reliable and valid index for measuring quality of care, with potential for practical application in management of health services. PMID- 8514498 TI - Predicting the performance of a strategic alliance: an analysis of the Community Clinical Oncology Program. AB - OBJECTIVE: This study is designed to examine the effects of environment and structure of the Community Clinical Oncology Program (CCOP) on performance as measured by patient accrual to National Cancer Institute (NCI)-approved treatment protocols. DATA SOURCES/STUDY SETTING: Data and analysis are part of a larger evaluation of the NCI Community Clinical Oncology Program during its second funding cycle, June 1987-May 1990. Data, taken from primary and secondary sources, included a survey of selected informants in CCOPs and research bases, CCOP grant applications, CCOP annual progress reports, and site visits to a subsample of CCOPs (N = 20) and research bases (N = 5). Accrual data were obtained from NCI records. STUDY DESIGN: Analysis involved three complementary sets of factors: the local health care resources environment available to the CCOP, the larger policy environment as reflected by the relationship of the CCOP to selected research bases and the NCI, and the operational structure of the CCOP itself. A hierarchical model examined the separate and cumulative effects of local and policy environment and structure on performance. PRINCIPAL FINDINGS: Other things equal, the primary predictors of treatment accrual were: (1) the larger policy environment, as measured by the attendance of nurses at research base meetings; and (2) operational structure, as measured by the number and character of components within participating CCOPs and the number of hours per week worked by data managers. These factors explained 73 percent of the total variance in accrual performance. CONCLUSIONS: Findings suggest criteria for selecting the types of organizations to participate in the alliance, as well as for establishing guidelines for managing such alliances. A future challenge is to determine the extent to which factors predicting accrual to cancer treatment clinical trials are equally important as predictors of accrual to cancer prevention and control trials. PMID- 8514499 TI - Defining rural hospital markets. AB - OBJECTIVE: The purpose of this study is to examine the geographic scope of rural hospital markets. DATA SOURCES: The study uses 1988 Medicare patient discharge records (MedPAR) and hospital financial information (HCRIS) for all rural hospitals participating in the Medicare Program. STUDY DESIGN: Hospital-specific market areas are compared to county-based market areas using a series of geographic and socioeconomic-demographic dimensions as well as indicators of market competitiveness. The potential impact of alternative market configurations on health services research is explored by estimating a model of rural hospital closure. DATA COLLECTION/EXTRACTION METHODS: Hospital-specific market areas were defined using the zip code of patient origin. Zip code-level data were subsequently aggregated to the market level. FINDINGS: Using the county as the hospital market area results not only in the inclusion of areas from which the hospital does not draw patients but also in the exclusion of areas from which it does draw patients. The empirical estimation of a model of rural hospital closure shows that the definition of a hospital market area does not jeopardize the ability to identify major risk factors for closure. CONCLUSIONS: Market area definition may be key to identifying and monitoring populations at risk from rural hospital decisions to downsize or close their facilities. Further research into the market areas of rural hospitals that have closed would help to develop alternative, and perhaps more relevant, definitions of the population at risk. PMID- 8514500 TI - Choice of hospital for delivery: a comparison of high-risk and low-risk women. AB - OBJECTIVE: This article tests whether or not the factors that affect hospital choice differ for selected subgroups of the population. DATA SOURCES: 1985 California Office of Statewide Health Planning and Development (OSHPD) discharge abstracts and hospital financial data were used. STUDY DESIGN: Models for hospital choice were estimated using McFadden's conditional logit model. Separate models were estimated for high-risk and low-risk patients, and for high-risk and low-risk women covered either by private insurance or by California Medicaid. The model included independent variables to control for quality, price, ownership, and distance to the hospital. DATA EXTRACTION: Data covered all maternal deliveries in the San Francisco Bay Area in 1985 (N = 61,436). ICD-9 codes were used to classify patients as high-risk or low-risk. The expected payment code on the discharge abstract was used to identify insurance status. PRINCIPAL FINDINGS: The results strongly reject the hypothesis that high-risk and low-risk women have the same choice process. Hospital quality tended to be more important for high risk than low-risk women. These results also reject the hypothesis that factors influencing choice of hospital are the same for women covered by private insurance as for those covered by Medicaid. Further, high-risk women covered by Medicaid were less likely than high-risk women covered by private insurance to deliver in hospitals with newborn intensive care units. CONCLUSIONS: The results show that the choice factors vary across several broadly defined subgroups of patients with a specific condition. Thus, estimates aggregating all patients may be misleading. Specifically, such estimates will understate actual patient response to quality of care indicators, since patient sensitivity to quality of care varies with the patients' risk status. PMID- 8514501 TI - Effect of a community health center intervention on breast cancer screening among Hispanic American women. AB - OBJECTIVE: A multiple component intervention in a community health center is presented, and its effect on breast cancer screening participation by Hispanic American women between the ages of 45 and 75 years is discussed. DATA SOURCES/STUDY SETTING: In 1990, data were collected through a retrospective audit (at least as far back as 1987) of community health center medical records, as well as from a client referral log. The health center, located in a small Massachusetts city, primarily serves clients of Latino heritage. STUDY DESIGN: The study used a nonexperimental pretest-posttest intervention design to document clients' screening activities. To control for uneven length of enrollment, aging of the population, and sporadic utilization, the unit of analysis chosen for the principle study variables was an "eligible year." DATA COLLECTION: Variables of interest included screening (clinical breast exam and mammography), periodicity of screening, and compliance with referrals. PRINCIPAL FINDINGS: Postintervention, considerably greater screening mammography occurred among all age groups, more women had at least one screening mammogram during the period, more clinical breast exams included a mammogram referral, and the compliance rate improved. The rate of clinical breast exam did not significantly improve, showing a downward trend. PMID- 8514502 TI - Dynamic aspects of prescription drug use in an elderly population. AB - OBJECTIVE: This study explores longitudinal patterns in outpatient prescription drug use in an elderly population. DATA SOURCES/STUDY SETTING: Enrollment records and prescription drug claims were obtained for a sample of elderly Pennsylvanians (N = 27,301) who had enrolled in the Pharmaceutical Assistance Contract for the Elderly (PACE) program at any time between July 1984 and June 1987. Study Design. The study tracks monthly prescription fill rates for sampled PACE beneficiaries from their initial enrollment month through disenrollment, death, or the end of the study (whichever occurred first). We specify two-part multivariate models to assess the effect of calendar time, length of time in the PACE program, and progression to disenrollment or death both on the probability of any prescription use and on the level of use among those who filled at least one prescription claim per month. Control variables include age, gender, race, income, residence, and marital status. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from administrative files maintained by the PACE program, checked for errors, and then formatted as person-month records. PRINCIPAL FINDINGS/CONCLUSIONS: We find a strong positive relationship between drug use and the length of time persons are PACE-enrolled. Persons whose death occurs within a year have much higher prescription utilization rates than do persons whose death is at least a year away, and the differential increases as death nears. Persons who fail to renew PACE coverage use significantly fewer prescription drugs in the year prior to disenrollment. Holding age and other factors constant, we find that average levels of prescription use actually declined over the study period. PMID- 8514503 TI - Tunnel vision. PMID- 8514504 TI - Getting it all together. Interview by Nick Robin. PMID- 8514506 TI - Community inexperience. PMID- 8514505 TI - Beyond Project 2000. PMID- 8514507 TI - Top of the agenda. PMID- 8514508 TI - Mega-merger boosts GP monopoly. PMID- 8514509 TI - School nursing--fighting for the future. PMID- 8514510 TI - Policy: changing attitudes to children. PMID- 8514511 TI - Skill mix: value for whom? PMID- 8514512 TI - Behavioural treatment for sleep disturbance. PMID- 8514513 TI - Tackling sleep problems through clinic-based approach. PMID- 8514514 TI - Tracing the tradition of health visiting. PMID- 8514515 TI - Promoting the role of health visitors to general practice staff. PMID- 8514516 TI - Information--getting the systems right. PMID- 8514517 TI - Grading--spinal attack. PMID- 8514518 TI - What has skill mix got to do with improving client care? PMID- 8514519 TI - [Perspectives of minimally invasive surgery in the area of the head and neck]. PMID- 8514520 TI - [Recommendations for the physician's patient education consultation with laryngeal and pharyngeal cancer patients]. PMID- 8514521 TI - [Physical and chemical aspects of ionomer bone implants]. AB - Polymaleinate ionomer (Ionocem) is a new bone replacement material for head and neck surgery. Ionomeric cement sets during a neutralization reaction of an alkaline glass with a polyalkenoic acid. No unphysiological heat is created during setting. Ionocem hardens in a bony defect in about 5 minutes. Molding, shaping, drilling and adding of new unset viscous cement applied to already hardened cement is easily possible in surgery. Ionocem is biocompatible, biostable and well tolerated by bone and soft tissues. Ionocem is adhesive to bone, offering new possibilities in reconstructive head and neck surgery. Devices can be fixed in place with the cement, bony structures anatomically reconstructed and CSF fistulas permanently closed. PMID- 8514522 TI - [Yellow light laser photocoagulation of vascular malformations in the head and neck area]. AB - Laser surgery techniques have become well established in otolaryngology. Yellow light lasers emit light in the visible spectrum. Laser light in the spectrum of 380-700 nm shows different effects after absorption at a specific chromophore. For the treatment of vascular lesions of the skin controlled absorption of energy by blood is necessary to avoid uncontrolled damage and vaporization. Chromophores of the skin which absorb energy transmitted by laser light are hemoglobin, bilirubin, oxyhemoglobin, beta carotene, collagen and melanin. The penetration of the laser light depends on its wavelength. In vascular lesions oxyhemoglobin is the chromophore whereas melanin is the chromophore in pigmented malformations. The argon-pumped dye laser, copper vapor and flash-lamp pumped dye laser emit laser light of 577, 578 and 585 nm. These lasers are especially useful for photocoagulation of oxyhemoglobin and for selective destruction of vascular tissue. The risk of hypotrophic or hypertrophic scarring is minimal (< 1%) because there is less alteration of the overlying dermis. The aim of the present study was to test, in a clinical setting, the copper vapor laser in vascular lesions of the head and neck. PMID- 8514523 TI - [Intraoperative monitoring of the facial nerve in transtemporal surgery of acoustic neurinoma]. AB - Acoustic neuroma ablation by the enlarged middle cranial fossa approach results in a low incidence of postoperative facial nerve dysfunction. In 25 consecutive patients with tumors in the cerebellopontine angle with a diameter up to 2.3 cm, intraoperative monitoring of the facial nerve was evaluated. The facial nerve was monitored electrophysiologically with recordings of the spontaneous EMG and electrically evoked potentials (CMAP) from at least three groups of facial muscles. In 4 cases monitoring was helpful for identification and delineation of the facial nerve. The mechanically elicited potentials during tumor preparation and CMAP after electrical stimulation close to the brain stem were compared with the postoperative facial nerve function and the time course of recovery. If the ongoing EMG recordings resulted in potentials below 0.5 mV and the CMAP at the end of tumor preparation was higher than 0.5 mV, facial nerve function was normal in 9 of 10 cases on the first postoperative day. One patient had mild facial palsy. Poor results could be predicted if numerous discharges with amplitudes higher than 0.5 mV and affected CMAP after stimulation near the brain stem were found at the end of surgery. All 3 patients with these findings had facial paralysis at hospital discharge (an average of 9 days after the operation). Recovery from the palsies was found to be prolonged. Intraoperative monitoring of the facial nerve is now used routinely in surgery of the cerebellopontine angle and the internal auditory canal. PMID- 8514524 TI - [Clinical experiences with dehydrated temporalis fascia in tympanoplasty. Early and late results]. AB - Dehydrated temporalis fascia, an allograft transplant tissue, is very useful in tympanoplasty and tympanomeatoplasty. In 87% of cases tympanic membrane grafts placed in patients with severe chronic otitis media have remained healed without change 4-6 years after surgery. All grafts also remained in position when placed on the posterior wall of the external auditory canal. Good healing was always seen without complications or inflammations. By using these grafts the duration of surgery could be reduced and the cosmetic risk of extending pre- or postauricular incisions to obtains autologous temporalis fascia was unnecessary, especially in revision surgery. The allograft is very easy to handle and is malleable and flexible. The main indications for use of allograft temporalis fascia are patients with chronic otitis media, traumatic tympanic membrane perforations or malformations of the middle ear (such as congenital atresias) requiring tympanic membrane replacement and lining of the posterior wall of the external auditory canal. PMID- 8514525 TI - [Use of a Ca(++) antagonist in noise-induced hearing loss in animal experiment]. AB - Hearing thresholds at 1-2-4-6 and 8 kHz were determined by brainstem evoked response audiometry (BERA) in 24 guinea pigs. The animals were then divided into 6 groups. Group 1 (controls) received no drugs and were not exposed to noise. Group 2 were given 15 mg/24 h/kg diltiazem s.c. for 13 days. Group 4 was exposed to the same noise as group 3 but was also treated with diltiazem 15 mg/kg/24 h from three days before noise exposure until the end of the experiment. Group 5 was exposed to a 110 dB SPL broad-band noise for 3 h daily for 10 days. Group 6 was exposed to the same noise as group 5 and was treated with diltiazem 15 mg/kg/24 h from three days before noise exposure until the end of the experiment. After the last noise exposure hearing thresholds were determined again by BERA and were found to be unchanged in those animals treated with the drug alone and the controls. In those groups with drug administration and noise exposure hearing loss was less than in the animals exposed to noise alone. This difference was more pronounced in the 90 dB groups than in the 110 dB groups. PMID- 8514526 TI - [Subjective attitudes of laryngectomized patients of the cause of the tumor disease. Correlation with psychosocial adjustment and pre- and postoperative alcohol and tobacco consumption]. AB - One or two days before operation 62 male patients with laryngeal or pharyngeal malignancies were questioned about their subjective beliefs concerning the causes of their cancer. Additionally they were asked about their current and past tobacco and alcohol consumption. Six months after the operation 51 of the 62 patients were interviewed about their psychosocial adjustment and their postoperative tobacco and alcohol consumption. Before the operation most of the patients (81%) reported that they already had been thinking about the possible causes of their malignant disease. Four out of five patients were smokers and consumed alcohol daily, at least until disease onset. According to psychiatric criteria more than 50% of the daily alcohol consumers were diagnosed as alcoholics. As was expected, "smoking" was rated as the most important causal factor in tumor etiology. Furthermore, "air pollution", "unhealthy working conditions" and "fate" were rated as important pathogenic factors of the individual cancer. Surprisingly "alcohol" was only rated as an important causal factor by a few patients. The causal factor "smoking" was correlated neither with actual pre- and postoperative smoking behavior, nor with postoperative psychosocial adjustment. "Alcohol" was positively associated with a postoperative reduction of alcohol consumption, on the one hand, and with increased postoperative psychological distress, on the other. Significant positive relationships were also found between "fate" and postoperative psychological distress and rejection of altered voice (e.g. laryngectomy). In conclusion, medical information about the possible causes of cancer should try to focus the attention of the patients on current and future stress factors and not on past risk behavior (e.g. alcohol and tobacco consumption), which cannot be altered retrospectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514527 TI - [Pedicled and microvascular reanastomosed transplants for reconstruction in the head-neck area]. AB - The introduction of the pectoralis major myocutaneous flap has opened up new dimensions for reconstruction following radical resection of advanced oral and pharyngeal malignancies. We report our 12-year experience with 89 patients in whom reconstruction with a pectoralis major flap was performed. The advantage of this technique is that it involves a single-stage reconstruction; moreover, the carotid artery is protected after neck dissection and soft tissue defects can be remodelled with the added bulk of the myocutaneous flap. On the other hand, the applicability of the technique is limited by the rigidity of the flap and the length of the vascular pedicle. These problems were solved by free tissue transfer. The excellent functional and aesthetic results of reanastomosed transplants have led to the myocutaneous pectoralis major flap being replaced at the Department of Otolaryngology in Tubingen. PMID- 8514528 TI - [Anaerobic infections in the head and neck area. Current status of knowledge]. AB - The classification of anaerobic infections and the most common organisms affecting the head and neck, pathogenesis diagnosis and current therapy are reported. Certain types of infections are particularly important for anaerobic bacteria and include actinomycosis, infectious complications of chronic otitis media or sinusitis, phlegmon of the floor of the mouth, peritonsillar abscess, retro-(para-)pharyngeal abscess, neck space infections, mediastinitis, wound infections following head and neck surgery and septic complications. PMID- 8514529 TI - Nephrology/hypertension/fluid and electrolyte disorders. AB - The following annotated bibliography has been developed for the purpose of providing to primary care physicians a handy source of review articles and major studies in the field of nephrology, hypertension, and fluid and electrolyte disorders. Almost all of the articles are review articles of clinical topics that would be of interest to the practicing physician. JAOA will be publishing additional annotated bibliographies in various fields of internal medicine over the next several months. This is the second in the series. Part 1 appeared in the January 1993 issue (93:50-65). Others will appear in forthcoming issues of THE JOURNAL. PMID- 8514530 TI - Treating nocturnal asthma poses challenges. PMID- 8514531 TI - Outcomes assessment: 'buzz words' in medical education whose time has come. PMID- 8514532 TI - Day-night variation of airways status in sympathomimetic- and theophylline treated asthma patients. AB - Eleven diurnally active asthma patients having a history of nocturnal asthma and treated regularly with albuterol or metaproterenol alone or with twice-daily sustained-release theophylline were evaluated for day-night pattern in peak expiratory flow (PEF) and use of supplemental beta-agonist aerosol for relief of acute asthma. Overall, significant day-night variation was observed in the supplemental use of beta-agonist medication and in airway patency. The patients managed by albuterol or metaproterenol alone used supplemental beta-agonist medication significantly more between 4 AM and 8 AM and also 8 PM and midnight in comparison to 4 PM to 8 PM; this was not true for those treated with both theophylline and beta-agonist aerosol. In patients taking a beta-agonist bronchodilator, the 24-hour mean PEF was greater than in those who also took theophylline, but the day-night variation in PEF was comparable. Supplemental isoproterenol use was significantly correlated with circadian amplitude of the PEF rhythm, but not with the 24-hour mean PEF. The greater the day-night variation in PEF, the greater the reliance on a supplemental beta-agonist bronchodilator. PMID- 8514533 TI - Thoracic outlet syndrome--a myofascial variant: Part 3. Structural and postural considerations. AB - Thoracic outlet syndrome involves more than just local neurovascular compression. Myofascial release treatments and stretching exercises may be only partially or temporarily successful unless all related components of somatic dysfunction, including craniosacral mechanisms, are addressed. Structural and postural abnormalities in the frontal plane, as with a short leg, and in the sagittal plane, such as lumbopelvic imbalances, as well as neural involvement all contribute to thoracic outlet syndrome symptoms. Once segmental restrictions are treated and symptoms diminish, postural correction and strengthening exercises may be initiated. Osteopathic diagnosis and treatment of the local, regional, and remote structural problems is necessary for optimal treatment of thoracic outlet syndrome and the maintenance of a symptom-free status. PMID- 8514534 TI - Assessing outcomes of the educational program of the West Virginia School of Osteopathic Medicine. AB - In education, "assessment" refers to the ongoing, systematic process of identification of goals, development of methods for measuring progress toward attaining those goals, and use of resulting information to make revisions in educational programs. Recently, state-review programs and accrediting agencies have focused review efforts on outcomes of the educational process. The West Virginia School of Osteopathic Medicine has developed a successful outcomes assessment program that includes information regarding graduates' activities. The school is now considering new programs regarding more comprehensive assessment of clinical outcomes. PMID- 8514535 TI - Procedures to follow when dismissing an intern or resident. AB - Rarely, interns or residents may be unable or unwilling to perform satisfactorily in a graduate medical education program. In such instances, the director of medical education or residency director (or both) must inform the trainee of his or her deficiency and provide appropriate counseling, generally with the opportunity for remediation. If dismissal becomes necessary, due process must be followed, and the institution must keep documentation that appropriate procedures were followed. These necessary procedures are outlined herein. PMID- 8514536 TI - The lupus anticoagulant and pregnancy. AB - The lupus anticoagulant has been understood for more than 40 years. However, reports of obstetric cases, although available, are not frequent. The author reviews the literature on this subject, including current recommendations on managing the problem in pregnancy. He reports a single case that involved a spontaneous abortion and a subsequent pregnancy in the same person. The second pregnancy during which the patient received prednisone and aspirin therapy, had a successful outcome. PMID- 8514537 TI - Neurogenic pulmonary edema. AB - Neurogenic pulmonary edema is a potential complication of severe central nervous system insult. In the patient described, neurogenic pulmonary edema resulted from gunshot injuries to the head. Aggressive supportive care and intravenous administration of dopamine successfully resolved this pulmonary complication. Although such treatment is crucial in patients with possibly reversible central nervous system injury, the patient described had irreversible brain injury. The authors discuss current theories of the pathogenesis as well as diagnosis and treatment options. PMID- 8514538 TI - A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. CNS Cancer Consortium. AB - PURPOSE: The object of this study was to ascertain the value of topical ascorbic acid in the prevention of radiation dermatitis. METHODS AND MATERIALS: Patients with primary or metastatic brain tumors were eligible. Patients applied a topical solution, twice per day prior to and throughout the course of radiotherapy, to the left and right sides of the head. The radiotherapist and the patient were blinded as to the contents of the solutions. The bottle for one side of the head contained topical ascorbic acid solution. The bottle for the other side of the head contained only vehicle. During and after the course of treatment the radiotherapist scored the skin reaction on both the left and right sides of the irradiated head using a skin reaction scale. The data were analyzed with a matched pair analysis. Since each patient received both treatments (ascorbic acid and control solutions) the statistical analysis concentrated on the paired difference in scores based on the probability of a "preference" for the treatment or control. RESULTS: Eighty-four patients entered the study. Sixty-five were suitable for analysis. In 10 patients there was a preference for ascorbic acid solution (15%), in 20 patients there was a preference for placebo (31%), and there was a preference for neither in 35 patients (54%). Ascorbic acid solution could be considered to have an effect if the percentage of preferences favoring ascorbic acid over placebo, among those subjects with a preference, significantly exceeded the 50% expected by chance. The observed percentage of preferences for ascorbic acid was only 33% (10 of 30 with a preference; p = .10, two-sided sign test). Patient age, race, sex, and total dose of irradiation had no detectable influence on the comparative skin toxicity scores. CONCLUSION: There is no discernible benefit to ascorbic acid lotion, in the manner in which we used it in this trial, for the prevention of radiation dermatitis. PMID- 8514539 TI - Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor. AB - PURPOSE: This study was conducted to examine the radioprotective and radiochemoprotective capabilities of interleukin 1 beta (IL-1) on two acute reacting normal tissues of the C3H mouse, the mucosa of the lip and the duodenum. Also assessed was the modulating effect of IL-1 on tumor growth in the same strain of mice. METHODS AND MATERIALS: IL-1 was administered to C3H/Km mice in combination with fractionated irradiation, or with cyclophosphamide, cisplatin, or 5-fluorouracil (5FU) followed by irradiation. Normal tissue damage was evaluated in the mouse lip, using a subjective scoring system for tissue reaction, and in the duodenum, using the crypt cell survival assay. RIF-1 fibrosarcoma tumor response was assayed with the regrowth delay method. RESULTS: IL-1 protected against the acute reaction produced by fractionated irradiation in the lip mucosa, shifting the dose-response curve by 3.8 Gy. IL-1 was protective when injected intraperitoneally 24 hr before CY or c-DDP, which were given immediately before the first of five daily radiation dose fractions. The dose response curves for cyclophosphamide and cisplatin were shifted 4.0 Gy and 1.6 Gy, respectively. IL-1 did not protect against 5FU toxicity when treatments were administered in that same sequence; however, when 5FU was given 4 or 8 hr before IL-1 and the first radiation dose fraction followed 20 or 16 hr later, there was significant protection and the curves were separated by 1.5 Gy or 3.5 Gy. IL-1 also protected duodenal crypt cells against the cytocidal effect of fractionated irradiation, with a dose difference of 1.5 Gy and an improvement of crypt survival of 11.7%. It was even more protective for these cells against the enhanced drug toxicity when cyclophosphamide or 5FU were administered immediately before the first of five daily radiation doses, with the dose differences of 4.4 and 5.3 Gy, respectively, and improvements of crypt survival of 33.8 and 29.9%, respectively. There was no modification by IL-1 of the effect of irradiation alone on the RIF-1 tumor. CONCLUSION: This study demonstrates the potential for use of IL-1 as an auxiliary in combinations with chemotherapeutic agents and radiation. It also indicates that for some drugs, such as 5FU, IL-1 effects may be sequence dependent. PMID- 8514540 TI - Failure of hyperfractionated radiotherapy to reduce bone growth arrest in rats. AB - PURPOSE: Radiotherapy of the craniospinal axis is causing an age dependent growth arrest in children. The purpose of this paper was to examine in an animal model, whether hyperfractionated radiotherapy, given with twice daily fractions in conventional overall treatment time, would cause less growth arrest of the spinal column than a regular treatment schedule. METHODS AND MATERIALS: The time-dose fraction schedule for the treatment of the craniospinal axis of children with medulloblastomas was used as model for the treatment of the spine in rats. The entire spine of weanling rats received either 3570 cGy in 21 daily fractions of the 170 cGy, 5 times per week over 27 days, or 3630 cGy in 33 fractions of 110 cGy, given twice daily with 6-hr intervals over 21 days. RESULTS: Both fraction schedules were isoeffective and caused a growth inhibition of 9.5%. The growth arrest was complete after 1870-2420 cGy. The alpha/beta ratio for the growing rat vertebrae was 3400 cGy. This result contrasts with the growth sparing effect observed with hyperfractionation of accelerated treatment schedules. CONCLUSION: Growing bone is a fast proliferating tissue. Hyperfractionation with 110 cGy BID compared to 170 cGy given once a day, has no sparing effect on bone growth in rats if given in conventional overall treatment time. PMID- 8514541 TI - Radiosensitization by a new potent nucleoside analog: 1-(1',3',4'-trihydroxy-2' butoxy)methyl-2-nitroimidazole(RP-343). AB - PURPOSE: A new hypoxic cell sensitizer has been synthesized; this is a 2 nitroimidazole nucleoside analog having erythritol as a sugar moiety at the N-1 position of the imidazole ring (RP-343). Its possibility as a potent hypoxic cell sensitizer was compared with those of RP-170 and etanidazole. METHODS AND MATERIALS: Radiosensitization was tested in two murine tumors, EMT6 using in vitro and in vivo-in vitro assays and SCCVII using growth delay and TCD50 assays. Pharmacokinetic study was performed in Balb/c mice bearing EMT6 tumors and in Beagle dogs. LD50 of each sensitizer was obtained with ICR mice. RESULTS: As might be expected from the almost identical electron affinities of the three sensitizers, they were equally effective against hypoxic EMT6 cells in vitro. While having the lowest partition coefficient (0.035), RP-343 exhibited almost equally effective distribution to tumors and sensitizing radiation activity. An intravenous (i.v.) injection of 100 mg/kg of RP-343, RP-170 and etanidazole showed an almost equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.33-1.44 to solid SCCVII tumor under both tumor growth delay assay and TCD50 assay. A great advantage of RP-343 over RP-170 and etanidazole is its very much lower toxicity; their LD50 in mice were > 6.0, 4.3 and 4.8 g/kg, respectively, on i.v. injection. The lower toxicity of RP-343 was supported by its lower concentrations in the brain; the RP-343 AUC for brain was 0.43 times that of RP-170. Three indices were selected to compare the three nitroimidazoles. SER at 5% LD50 doses of RP-343, RP 170 and etanidazole was 1.66, 1.59 and 1.56. At the same toxicity levels, RP-343 was found to have better sensitization of solid tumors over both etanidazole and RP-170. The maximum tumor concentration/AUC for brain (Cmax,tumor/AUCbrain) ratios for RP-343 and RP-170 were 9.62 and 3.98. CONCLUSIONS: This extremely high ratio of RP-343 could explain its lower toxicity than RP-170 or etanidazole. The therapeutic risk index defined as D1.5/LD50 (D1.5 is the sensitizer dose to obtain the SER of 1.5 in vivo) for RP-343, RP-170 and etanidazole were 0.022, 0.033 and 0.036, respectively. Especially, the effectively lower therapeutic risk index for RP-343 presents the possibility of clinical advantage over etanidazole. PMID- 8514542 TI - Combination of aziridinylbenzoquinone and cis-platinum with radiation therapy in the 9L rat brain tumor model. AB - PURPOSE: We evaluated the potentiating effects of aziridinylbenzoquinone (AZQ) and cis-platinum on the prolongation of survival by radiation therapy in a rat brain tumor model. METHODS AND MATERIALS: On day 10 following intracranial inoculation of the 9L gliosarcoma, Fischer 344 rats were treated with radiation therapy (Cesium-137 source irradiator) and/or chemotherapy delivered either systemically (intraperitoneal or intravenous), or intracranially directly into the tumor in a volume of 5 microliters. Increased life spans were calculated relative to the median survival time for the control (ILS-C) or to the median survival time for radiation therapy only (ILS-RT) group. RESULTS: Median survival time for untreated rats was 22 +/- 3 days for seven experiments. Radiation therapy (16 Gy) produced a significant (p < 0.002) improvement in survival, with an average ILS-C of 75 +/- 19%. Systemic AZQ (1 or 5 intravenous injections of 0.5 mg/kg) produced ILS's of 0 and 23%, the latter being significant (p = 0.002). When added to radiation therapy, there were further improvements (ILS-RT's of 47 and 72%), but these were not significant. Intratumor AZQ (40 or 50 micrograms intracranially) produced significant ILS-C's of 30 and 33% (p = 0.01 and 0.0002, respectively). Added to radiation therapy, intracranial AZQ produced improvements (ILS-RT's of 5 and 102%), with only the latter being significantly improved (p = 0.009). Cis-platinum (3 micrograms intracranially) produced ILS-C's of 13 and 6%, neither significantly different from controls. Added to radiation therapy, cisplatinum caused improvements (ILS-RT's of 18 and 64%), with only the latter significant (p = 0.049). CONCLUSION: These results demonstrate that AZQ delivered systemically, and AZQ and cis-platinum delivered intracranially, can produce statistically significant improvements in the survival of rats burdened with the 9L brain tumor. The agents delivered intracranially significantly potentiated the prolongation of survival obtained by radiation therapy. This preclinical evidence suggests that combining radiation therapy with these cytotoxic chemotherapeutic agents may benefit patients with high-grade malignant brain tumors. PMID- 8514543 TI - Radiation induced lumbosacral plexopathy in gynecologic tumors: clinical findings and dosimetric analysis. AB - PURPOSE: Radiation-induced lumbosacral plexopathy is a rare complication of pelvic irradiation. METHODS AND MATERIALS: We report four cases among 2,410 patients treated to the pelvis for carcinoma of the cervix and carcinoma of the endometrium. All patients received both external beam and intracavitary radiation. The total calculated dose to the lumbosacral plexus was on the order of 7300 cGy. RESULTS: All 4 cases presented developed lumbosacral plexopathy. CONCLUSIONS: Although a few permanent lumbosacral lesions have been reported for patients treated with conventionally fractionated external beam, this syndrome is more often seen in patients treated with intracavitary irradiation for cervical or endometrial carcinoma. PMID- 8514544 TI - Gorham's massive osteolysis: the role of radiation therapy and a review of the literature. AB - PURPOSE: This paper reviews the natural history and management of patients with Gorham's disease and presents four cases treated at The Massachusetts General Hospital since 1965. Gorham's disease is characterized by localized endothelial proliferation which results in destruction and resorption of bone. The etiology is undefined. There is no evidence of a malignant, neuropathic, or infectious component. This disease is progressive in most patients, but in occasional instances the process has been noted to be self-limited. The principal treatment modalities are surgery and radiation therapy. METHODS AND MATERIAL: Since 1965, four patients with Gorham's Disease have been treated at the Massachusetts General Hospital. Three received definitive radiation therapy in doses ranging from 31.5 to 45 Gy. The fourth patient underwent surgery primarily. RESULTS: Three patients are currently alive and fully functional with no evidence of disease at last follow-up. The fourth patient died of progressive disease despite treatment with both radiation therapy and surgery. CONCLUSION: The prognosis for patients with Gorham's disease is generally good unless vital structures are involved. Due to the rarity of this entity, there is no standard therapy. Definitive radiation therapy in moderate doses (40-45 Gy in 2 Gy fractions) appears to result in a good outcome and few long-term complications. PMID- 8514545 TI - Optimized low dose rate pellet configurations for intravaginal brachytherapy. AB - PURPOSE: The objective was to identify configurations of low dose rate pellet sources that optimize short treatment length brachytherapy dose distributions for a set of four intravaginal applicators. METHODS AND MATERIALS: The method of simulated annealing was used. Dose rates at calculation points on the surface of 2.0, 2.5, 3.0, and 3.5 cm diameter applicators along a fixed 3.0 cm treatment length were optimized for Cs-137 sources of strengths 0.74 and 0.63 GBq in trains having maximum lengths of 3.0, 3.5 and 4.0 cm. Variations in the optimization algorithm involving two different objective functions and different combinations of selectable parameters were investigated in an effort to standardize the approach. RESULTS: An objective function based on the maximum dose rate difference at the calculation points in conjunction with a single parameter set proved suitable for all applicators. Optimized solutions involving both a single configuration of sources and a combination of two such configurations were successfully identified. The latter consistently afforded superior dose rate uniformity, particularly for the smaller diameter applicators. A maximum source train length of 3.5 cm was found to provide a good compromise between attaining dose rate uniformity along the 3.0 cm treatment length and minimizing irradiation of adjacent normal tissues. For each applicator, an optimized 3.5 cm pellet train yielded better surface dose rate uniformity than a corresponding optimum-length linear source. CONCLUSION: Pellet configurations that optimize dose distributions for intravaginal brachytherapy applicators can be reliably identified with modest computational effort using the method of simulated annealing. The method is therefore suitable for use in routine clinical treatment planning for this site. PMID- 8514546 TI - Positional stability of sources during low-dose-rate brachytherapy for cervical carcinoma. AB - PURPOSE: A presumed advantage of high dose rate gynecologic applicators is the fixed relationship maintained between applicator and anatomic structures during the brief exposure. However, it has never been demonstrated that movement of applicators during low dose rate procedures is significant. Therefore, we assessed the magnitude of changes in positioning and attendant alterations in dosimetry which occur during LDR applications. METHODS AND MATERIALS: Fifteen consecutive cervix cancer patients who were treated with combined external beam and brachytherapy (Fletcher-Suit-Delclos applicator), agreed to have orthogonal pelvic radiographs prior to after-loading and following removal of Cesium-137 sources. RESULTS: The median duration of the insertion was 56.5 hours. The average shift was 3.0 mm. Detailed analysis of source movement showed the following changes in median dose (external plus implant): point A, 1.4%; point B, 1.7%; point P, 0.9%; bladder point, 1.9%; rectal point, 2.6%. CONCLUSION: The geometric relationships between the intracavitary gynecologic applicator and the target tissue as well as the critical structures can be adequately maintained throughout the course of a low dose rate implant. Source movement does not result in significant dose changes in terms of decreased cure rates or added complications. Thus, while rationale for high dose rate applicators continues to be proposed, maintenance of a fixed geometric relationship should not be an impetus for the selection of high dose rate intracavitary applicators when treating cervical tumors. PMID- 8514547 TI - Concept of dose nonuniformity in interstitial brachytherapy. AB - PURPOSE: Evaluation of the 3-dimensional dose distributions of interstitial implants using the dose uniformity ratio. METHODS AND MATERIALS: Single source, two sources, three and four sources arranged both linearly and in the form of a triangle or a square, ribbons with different seed spacings, a single-plane and double-plane implants were evaluated. The evaluations involved the use of differential dose volume histograms and the dose nonuniformity ratio defined as the ratio of the high dose volume to the reference volume. RESULTS: For a single source, the dose nonuniformity is the same regardless which dose rate is selected as the treatment dose rate. For any multi-source implant, the dose nonuniformity is altered depending on the selection of the reference dose rate. In addition, the dose nonuniformity curve exhibited three characteristics zones. CONCLUSION: The dose nonuniformity ratio can be a useful tool in assessing and optimizing interstitial implants. PMID- 8514548 TI - The reliability of optimization under dose-volume limits. AB - PURPOSE: An optimization algorithm improves the distribution of dose among discrete points in tissues, but tolerance depends on the distribution of dose across a continuous volume. This report asks whether an exact algorithm can be completed when enough points are taken to accurately model a dose-volume constraint. METHODS AND MATERIALS: Trials were performed using a 3-dimensional model of conformal therapy of lung cancer. Trials were repeated with different limits placed on the fraction of lung which could receive > 20 Gy. Bounds were placed on cord dose and target dose inhomogeneity. A mixed integer algorithm was used to find a feasible set of beam weights which would maximize tumor dose. Tests of feasibility and optimality are introduced to check the solution accuracy. RESULTS: Solutions were optimal for points used to model tissues. An accuracy of 3-4% in a volume condition could be obtained with models of 450-600 points. The error improved to 2% with 800 points to model the lung. Solution times increased six-fold at this level of accuracy. CONCLUSION: The mixed integer method can find optimum weights which respect dose-volume conditions in usually acceptable times. If constraints are violated by an excessive amount, the optimization model should be rerun with more points. PMID- 8514549 TI - The effect of advanced age on the efficacy of radiation therapy for early breast cancer, local prostate cancer and grade III-IV gliomas. AB - PURPOSE: This study was undertaken to determine the effect of advanced age on radiation therapy outcomes for early breast cancer, local prostate cancer and Grade 3-4 gliomas of the brain. METHODS AND MATERIALS: Radiation therapy outcomes for three malignancies (N = 1,401) were determined for a geriatric cancer population defined as 70 years of age or older and compared to a non-geriatric cancer population defined as less than 70 years of age. The three patient groups studied were: (a) primary breast cancer patients with clinical Stage I or II disease treated with lumpectomy and radiation therapy (N = 994), (b) local prostate cancer patients with Stage A2, B, or C disease treated with radical radiation therapy (N = 294), and (c) patients with Grade 3-4 gliomas of the brain treated with high dose radiation therapy (N = 113). RESULTS: For Stage I and II breast cancer, there was no statistically significant difference in the overall 10-year survival rates (63% vs. 73%), 10-year cause-specific disease-free survival rates (70% vs. 63%), and 10-year local breast recurrence free survival rates (76% vs. 79%) comparing the geriatric cancer population to the non geriatric cancer population. For local prostate cancer, there was no statistically significant difference in the 10-year survival rates (38% vs. 41%) or in the 10-year cause-specific disease-free survival rates (58% vs. 52%) in the geriatric population compared with the non-geriatric population. On the other hand, the use of high dose radiation therapy for malignant gliomas resulted in statistically significant inferior 1-year (18% vs. 38%) and 2-year (0% vs. 10%) survival rates for the geriatric population versus the non-geriatric population. CONCLUSION: This study strongly supports the use of standard radiation therapy programs for early breast and prostate cancer patients age 70 years or more. However, our study raises questions about the efficacy of radiation therapy in patients over the age of 70 years with Grade 3-4 gliomas. PMID- 8514550 TI - Stage I, II seminoma--then and now. PMID- 8514551 TI - Late rectal bleeding following combined X-ray and proton high dose irradiation for patients with stages T3-T4 prostate carcinoma. AB - PURPOSE: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. METHODS: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10-25 MV photons (Arm 2). RESULTS: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangiectatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. CONCLUSIONS: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding. PMID- 8514552 TI - "What price greed?". PMID- 8514553 TI - More on self-mutilative behavior in horses. PMID- 8514554 TI - Mandatory sterilization. PMID- 8514555 TI - Mandatory sterilization. PMID- 8514556 TI - More on hemorrhagic complications attributable to certain drugs. PMID- 8514557 TI - More on material safety data sheets. PMID- 8514558 TI - Collective effort needed to unlock factors related to feline injection-site sarcomas. PMID- 8514559 TI - Zinc deficiency in swine related to eye damage. PMID- 8514560 TI - Veterinarian offers insight on mission in developing countries. PMID- 8514561 TI - Size and organization of private veterinary practices. PMID- 8514562 TI - Meeting with employees. PMID- 8514563 TI - An inside look at integration. PMID- 8514564 TI - Animal drug container labels: a guide to the reader. PMID- 8514565 TI - Drug availability: the real focus of the symposium. PMID- 8514566 TI - FDA responsibilities in regulation of drugs for use in animals: congressional perspective. PMID- 8514567 TI - History of extra-label use of animal drugs. PMID- 8514568 TI - FDA extra-label use policy: 1992 revisions. PMID- 8514569 TI - Extra-label use policy of the Canadian Bureau of Veterinary Drugs. PMID- 8514570 TI - Current FDA policy on use of human-labeled drugs in animals. PMID- 8514571 TI - Extra-label drug use--pharmaceutical industry view. PMID- 8514572 TI - Extra-label drug use--veterinary practitioner views: companion animals. PMID- 8514573 TI - Extra-label drug use--veterinary practitioner views: food animals. PMID- 8514574 TI - Extra-label drug use--veterinary practitioner views: laboratory animals. PMID- 8514575 TI - Extra-label drug use: the lifeblood of zoo animal and wildlife medicine. PMID- 8514576 TI - Extra-label drug use in aquaculture. PMID- 8514577 TI - Animals and the urban prism. PMID- 8514578 TI - AVMA legislative initiative. Special address. PMID- 8514579 TI - The AVMA legislative initiative. AB - The AVMA's legislative initiative impacts veterinarians, animal owners and producers, and the general public. The purpose of this report is to review the history that led to the AVMA's Executive Board decision in November 1991, to commit manpower and resources to seek a legislative solution to the dilemma facing veterinarians in choosing between following the letter of the law or their professional oath when use of a drug in an extra-label manner is indicated. This action resulted in the introduction into the 102nd Congress of 2 bills that would have codified existing FDA policy on extra-label use. This proposed legislation, in turn, encouraged an open forum on this issue. This report addresses some of the frequently voiced concerns including the scope of the legislation and its impact on public health. PMID- 8514580 TI - The AVMA legislative initiative: a legal overview. PMID- 8514581 TI - Use of FDA-approved drugs in veterinary medicine: prerogatives and responsibilities. PMID- 8514582 TI - The AVMA legislative initiative: practitioners' view. PMID- 8514583 TI - Producer industry views on the AVMA legislative initiative. PMID- 8514584 TI - The AVMA extra-label drug use legislative initiative: the American Kennel Club view. PMID- 8514585 TI - Food processor views on the AVMA extra-label drug use legislative initiative. PMID- 8514586 TI - Scientific basis for nonapproved use of drugs in veterinary practice. PMID- 8514587 TI - Availability and use of existing scientific information for responsible drug prescribing. PMID- 8514588 TI - The contribution of clinical pharmacology to new drug approvals. PMID- 8514589 TI - Increased approvals--myth or reality. PMID- 8514590 TI - Educating veterinarians to prescribe and use drugs in a responsible manner. PMID- 8514591 TI - Professional drug labeling. PMID- 8514592 TI - Implications for the FDA/Center for Veterinary Medicine (CVM). PMID- 8514593 TI - Assuring a residue-free food supply: milk. PMID- 8514594 TI - Assuring a residue-free food supply: beef. PMID- 8514595 TI - Assuring a residue-free food supply: pork. PMID- 8514596 TI - Assuring a residue-free food supply: special-fed veal. AB - The importance of extra-label drug use is discussed as this provision relates to special-fed veal production. Presently, there are 3 drugs approved and labeled for use in veal calves. Other medications and pharmaceuticals required to maintain and enhance calf health and well-being must be provided by consulting veterinarians under extra-label drug use provisions. Although special-fed veal has recently been reclassified as a minor use species (within Inter-Regional-4 designation), a sufficiently broad spectrum of safe and effective drugs will probably not be approved for use in veal calves within an acceptable and reasonable period. The use and practice of extra-label drug use provisions have apparently not represented a food safety hazard if the FSIS National Residue Program results are considered a measure of relative food safety. In 1988, the percentage of violative residues (based on all contaminants including antibiotics) was 3.3%; in 1991, this percentage was 0.24%. If existing extra label drug use provisions were antagonistic with continuing efforts to enhance food safety, the percentage of violative residues would not have decreased. Perhaps not coincidentally, a comprehensive Veal Quality Assurance Educational Program (VQAEP) also was initiated in 1988. This industry-funded, industry directed program is comparable to QAEP or total quality management programs conducted in other species and production systems. Over 80% of all US special-fed veal producers and others involved in the veal industry have participated in VQAEP seminars since 1988, with repeated attendance by many producers. Although the VQAEP has been effective, the goal of this and other programs must be zero violative residues. PMID- 8514597 TI - Responsibilities of food animal practitioners regarding extra-label use of drugs. PMID- 8514598 TI - Responsibilities under an amended Food, Drug & Cosmetic Act: equine practitioners. PMID- 8514599 TI - Responsibilities under an amended Food, Drug & Cosmetic Act: companion animal practitioners. PMID- 8514600 TI - Drug use guidelines for veterinary practitioners. PMID- 8514601 TI - Professional responsibilities. PMID- 8514602 TI - Transgenic cancer resistant mice carrying the E. coli O6-alkylguanine-DNA alkyltransferase gene, ada. PMID- 8514603 TI - Effect of mass screening for breast cancer from the aspect of psychosocial assessment of the quality of life. AB - To assess the quality of life (QOL) in patients with breast cancer receiving mass screening, a collaborative matched case-control study was conducted in nine hospitals throughout Japan. A total of 122 patients detected by mass screening (study group) and 226 patients found in out-patient clinics (control group) were assessed psychosocially on the basis of questionnaire information. The incidence of patients with early stage breast cancer was significantly higher in the study group than in the control group (P < 0.05). Chest wall pain was observed in 35.2% of the study group and in 46.5% of the control group (P < 0.05). Although control patients were more optimistic than study group patients, disturbed daily life and anxiety about recurrence were a little more frequent in the former group than in the latter. In particular, shoulder stiffness was frequently seen in the control group (P < 0.05). Early detection and information do not create anxiety in mass screening patients (P < 0.01). We should recommend mass screening to patients to detect early stage breast cancer and provide better QOL. PMID- 8514604 TI - Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia. AB - We have screened mutations of the N-ras gene at codons 12, 13, and 61 in leukemia cells obtained from 100 patients with acute myeloid leukemia (AML), and found mutated N-ras alleles in 9 patients. We further analyzed the polyclonality of multiple N-ras gene mutations in 4 AML patients. One patient, who had the monoclonal karyotype, t(11;17), had two types of double missense mutations at codons 13 and 61 in the same allele. Each of the remaining three patients, one of whom had t(15;17) with a monoclonal rearrangement of the retinoic acid receptor alpha and PML genes, carried two missense mutations in a relatively small population of leukemia cells. We have demonstrated that multiple clonality of the N-ras gene is occasionally observed in leukemia with a monoclonal karyotype. These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia. PMID- 8514605 TI - Variation in K-ras codon 12 point mutation rate with histological atypia within individual colorectal tumors. AB - To elucidate genetic alteration in relation to morphology and also to confirm more directly the proposed adenoma-carcinoma sequence, we analyzed thirty-eight colorectal "cancer in adenoma" lesions exhibiting areas of different atypia, in terms of K-ras codon 12 point mutation. The mutation incidence was 26.3% (10/38) for all cancerous areas. Well-differentiated and very well-differentiated carcinoma exhibited values of 17.6% (3/17) and 30.4% (7/23), respectively (statistically not significant). Positive cases of adenoma with severe atypia and adenoma with moderate or slight atypia were 26.7% (8/30) and 8.3% (3/36) respectively (statistically significant). Thus, K-ras point mutation, as indicated previously, may play an important role in the early stages of colorectal tumorigenesis. As for the nature of the mutation, GGT(Gly) to GAT(Asp) was the most frequent (80%). Eight cases had mutations concurrently in different areas of the same tumor and in all of these the mutation was homogeneous (6 cases to GAT, 1 case to TGT and 1 case to GTT). This provides genetic support for the "adenoma-carcinoma sequence" theory proposed on the basis of morphological considerations. All lesions with a mutation were of polypoid type, and no mutation was found in the flat type. PMID- 8514606 TI - Deletion mapping of chromosome 1p and 22q in pheochromocytoma. AB - To identify the localization of tumor suppressor genes, 22 pheochromocytomas (9 hereditary and 13 sporadic) were examined for loss of heterozygosity (LOH) on the short arm of chromosome 1 and on the long arm of chromosome 22 by using 11 polymorphic DNA markers on each chromosome arm. LOH on 1p was observed in 12 of 22 informative cases (55%) and on 22q in 8 of 20 informative cases (40%). There was no significant difference in the frequency of LOH on 1p or 22q between hereditary and sporadic cases. We could localize the commonly deleted regions as distal to D1S73 and proximal to D1S63 on 1p and distal to D22S24 and proximal to D22S1 on 22q. In addition, the relationship between LOH on 1p and 22q was studied in 20 pheochromocytomas which were informative for probes on both chromosome arms. Of eight tumors that showed LOH on 22q, allelic loss on 1p was also detected in seven. Thus, LOH on 22q was correlated significantly with LOH on 1p (P = 0.0249; Fisher's exact test). These results suggest that inactivation of multiple tumor suppressor genes may be required for development and progression of hereditary and non-hereditary pheochromocytoma. PMID- 8514608 TI - A case of squamous cell lung carcinoma with high concentration of parathyroid hormone-related peptide in serum and pleural effusion presenting hypercalcemia. AB - A 57-year-old man with lung squamous cell carcinoma revealed hypercalcemia, hypophosphoremia, elevation of nephrogenous cAMP and metabolic alkalosis. Serum parathyroid hormone (PTH) and 1,25(OH)2D3 concentrations were not elevated. These findings were consistent with those in humoral hypercalcemia of malignancy (HHM). PTH-related peptide (PTHrP) concentrations were determined using N- and C terminal specific radioimmunoassays (PTHrP-N, PTHrP-C), and elevation of both PTHrP-N and PTHrP-C concentrations in the serum was noted (PTHrP-N, 27 pmol/liter (normal < 5); PTHrP-C, 1408 pmol/liter (normal < 50)). High concentration of PTHrP (946 pmol/liter for PTHrP-N and 5983 pmol/liter for PTHrP-C) was also found in the pleural fluid obtained at autopsy. Immunohistochemical study, using paraffin-embedded sections of the tumor tissue obtained at autopsy, revealed numerous PTHrP-positive cells and expression of PTHrP gene was confirmed by Northern blot analysis. These findings indicate that PTHrP, produced in the tumor tissue, was secreted into the blood stream, which caused HHM in the patient. Gel permeation chromatography of the serum and pleural fluid revealed several peaks of both PTHrP-N and PTHrP-C. Molecular forms of PTHrP-N were larger than those of PTHrP-C in the serum as well as pleural fluid. These findings indicate that multiple forms of PTHrP molecules are present in the serum and pleural fluid. Granulocytosis was also noted in the patient. However, granulocyte- and granulocyte macrophage-colony stimulating factor were not detected in the serum, and the mechanism of the granulocytosis in the patient was unclear. PMID- 8514607 TI - The expression of invasive behavior of differentiated squamous carcinoma cell line evaluated by an in vitro invasion model. AB - In order to elucidate the factors contributory to the expression of invasiveness of oral squamous cell carcinoma, we conducted biochemical and morphological comparisons of well differentiated squamous carcinoma cell line OSC-19 (oral squamous cell carcinoma) and undifferentiated carcinoma cell line KB, both cultured on 3T3 cell-embedded collagen gel (in vitro invasion model). OSC-19 cells invaded 3T3 cell-embedded collagen gel, while KB cells and OSC-19 cells on 3T3 cell-free gel matrix were less invasive. Cultured OSC-19 cells were characterized by lower proliferating activity, lower secretion of laminin and higher secretion of fibronectin than those of KB cells. Although the basement membrane with deposition of laminin and type IV collagen was formed, it was discontinuous at the invasion front. Gelatin zymography and western blotting showed matrix metalloproteinases (MMP), i.e., 72 kDa gelatinase (MMP-2) and 92 kDa gelatinase (MMP-9). Gelatinolytic activity was assayed, and was higher in OSC 19 cells than in KB cells or OSC-19 cells of the 3T3 cell-free model. By immunohistochemical analysis, MMP-2-positive cells were found scattered in both cell lines without any preferential localization, and the positivity for MMP-9 was localized in the invasion front of OSC-19 cells. These results strongly suggest that the invasiveness of squamous cell carcinoma is well correlated with cell-matrix adhesion by fibronectin and with focal elaboration of metalloproteinases, especially MMP-9, which play a major role in degrading the extracellular matrix components. PMID- 8514609 TI - Enhancing effect of interleukin-2 on production of parathyroid hormone-related protein by adult T-cell leukemia cells. AB - Leukemic cells from patients with adult T-cell leukemia (ATL) can produce a calcium-regulating protein, parathyroid hormone-related protein (PTHrP). Moreover, it has been reported that ATL cells produce some cytokines besides PTHrP and that these cells respond to the T-cell growth factors, interleukin-2 (IL-2) and interleukin-4 (IL-4). To elucidate whether PTHrP produced by ATL cells is regulated by IL-2 or IL-4, we investigated the in vitro effects of IL-2 and IL 4 on the release of PTHrP. IL-2 increased the release of PTHrP into the conditioned medium from leukemic cells in some, but not all, ATL patients; however, IL-4 did not affect the PTHrP release. PTHrP messenger RNA (mRNA) levels were increased in ATL cells cultured in the presence of IL-2. These data suggest that IL-2 plays a role in the regulation of hypercalcemia by enhancing the production of PTHrP in ATL patients. PMID- 8514610 TI - Interleukin-2 prevents programmed cell death in adult T-cell leukemia cells. AB - Adult T-cell leukemia (ATL) is a prototype of the lymphoma/leukemia syndromes involving immunologically mature T-lymphocytes. The first retrovirus described in humans, HTLV-1, is causally related to the disease. In this study, we examined whether ATL cells die in vitro through programmed cell death (PCD), which has been shown to occur in cells affected by several other acute and chronic leukemias. When ATL cells from peripheral blood were cultured in serum-free complete medium, a substantial proportion of them spontaneously died by PCD. After 48 h of culture, approximately 30% of the total DNA was fragmented. Electrophoresis indicated that the DNA of the ATL cells had been cleaved into regular oligonucleosome fragments each comprising approximately 180-200 base pairs. This process was significantly promoted by methylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in at least some cases. Since all ATL cells possess interleukin-2 receptors on the cell membrane, the effect of IL-2 on spontaneous PCD was assessed. PCD after 48 h of culture was inhibited by 30-50% by 100 U/ml interleukin-2 (IL-2). This effect of IL-2 to prevent spontaneous PCD was dose- and time-dependent. These findings suggest that the viability of ATL cells in vivo is regulated positively and negatively by intrinsic IL-2, glucocorticoid and regulators of PKA activity. Furthermore, the process of cell death may be involved in the development of the disease. PMID- 8514611 TI - Effect of accessory cells on stimulation of murine T-cell leukemia with antibodies to the CD3/T cell antigen receptor complex. AB - Stimulation of EL4 and RL male 1 leukemia cells in vitro with immobilized anti CD3 epsilon monoclonal antibody (mAb) (145-2C11) or anti-TCR beta mAb (H57-597) in the absence of accessory cells induced interleukin-2 (IL-2) production, and caused growth inhibition. The growth inhibition was, however, transient and the tumors started to grow again within 5 days in immobilizing plates treated with antibodies at concentrations of 2.5-100 micrograms/ml. Addition of mitomycin C treated accessory cells to the culture inhibited IL-2 production and resulted in augmented and persistent growth inhibition. No recovery of tumor growth was observed. Furthermore, DNA from EL4 and RL male 1 leukemia cells stimulated with anti-CD3/TCR mAbs was fragmented even in the absence of accessory cells, but fragmentation was much greater in the presence of accessory cells. Marginal and high expression of the bcl-2 gene were observed in EL4 and RL male 1, respectively, indicating that apoptosis of these leukemias mediated by signalling through the CD3/TCR complex has no direct relationship with expression of the bcl 2 gene. PMID- 8514612 TI - Lysosome labilizers potentiate the antitumor effects of tumor necrosis factor alpha. AB - Enhancement of in vitro cytotoxic activity of tumor necrosis factor-alpha (TNF alpha) was observed in combination with lysosome labilizers, particularly with urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t PA) and lipoprotein lipase (LPL). The concentration of TNF-alpha resulting in 50% cytotoxicity to L929 cells was only 20-30% of the value for TNF-alpha alone, when used in combination with a nontoxic dose of u-PA, t-PA or LPL. Furthermore, combined intravenous (i.v.) administration of TNF-alpha (3.5 x 10(5) U/mouse) and u-PA (300 IU/mouse) markedly increased the in vivo antitumor activity of TNF alpha to Meth A tumors transplanted into BALB/c mice; the tumor weight in co administered mice was about 40% of that in mice given TNF-alpha alone on day 6. The combination therapy of TNF-alpha (7.0 x 10(4) U/mouse, i.v.) and u-PA (300 IU/mouse, i.v.) was also effective for L929 tumors in Crj:CD-1(1CR)-nu nude mice compared with the conventional therapy with TNF-alpha alone. These results suggest that the combination of TNF-alpha and lysosome labilizers is a promising antitumor therapeutic regimen with clinical potential. PMID- 8514613 TI - Effects of chemoendocrine therapy on the coagulation-fibrinolytic systems in patients with advanced breast cancer. Japan Advanced Breast Cancer Study Group and Japan Clinical Oncology Group. AB - In order to predict a hypercoagulable state in patients with advanced breast cancer receiving medical treatment, the effects of chemoendocrine therapy on the coagulation-fibrinolytic systems were investigated prospectively. The patients were randomly divided into two groups. The ACT group had 38 patients, who received 20 mg/m2 adriamycin (ADM) i.v. on days 1 and 8, 100 mg cyclophosphamide (CPA) p.o. on days 1-14, and 20 mg tamoxifen (TAM) p.o. daily. The ACM group had 44 patients, who received 20 mg/m2 ADM i.v. on days 1 and 8, 100 mg CPA p.o. on days 1-14 and 1200 mg medroxyprogesterone acetate (MPA) p.o. daily. The treatment was repeated every 28 days until there was evidence of progressive disease or until the full ADM dose (550 mg/m2) had been given. The following 9 hematologic parameters were measured every 4 weeks: alpha 2-plasmin inhibitor plasmin complex (PIC), anti-thrombin-III (AT-III), D-dimer (Dd), fibrinogen (Fg), plasminogen (Pg), protein C (PC), thrombin-antithrombin-III complex (TAT-III), tissue plasminogen activator (t-PA), and factor X (FX). Compared to the ACT group, patients in the ACM group showed significantly higher values of AT-III and PC, which exceeded the normal ranges. The levels of Pg, t-PA and FX were significantly higher in the ACM group than in the ACT group, but were still within the normal ranges. The levels of TAT-III, Dd and PIC decreased in the ACT group and were unchanged in the ACM group after the start of treatment. Fg remained unchanged in both groups after the start of treatment. One patient in the ACM group had thrombophlebitis of the lower extremities with high levels of TAT-III, Dd and PIC and a decrease of Fg, but her condition returned to normal after reduction of the MPA dose. Although these data are not directly indicative of a hypercoagulable state in patients receiving chemoendocrine therapy, changes in AT-III, TAT-III, Dd and PIC should be monitored carefully when this type of treatment is given. PMID- 8514614 TI - Pharmacokinetic evaluation of (glycolato-O,O')diammine platinum(II) in lung lymph in sheep. AB - The pharmacokinetics of (glycolato-O,O')diammine platinum(II) (254-S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis-diamminedichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254-S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254-S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254-S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254-S and CDDP seemed to be caused by differences in their strength of protein binding; the association constants of 254-S for plasma and lymph protein were much less than those of CDDP. From these results, 254-S may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis. PMID- 8514615 TI - Ductectatic-type mucinous cystadenoma and cystadenocarcinoma of the human pancreas: a novel clinicopathological entity. AB - A new type of mucinous cystic pancreatic neoplasm is described. The lesions, which have been recognized only recently with the progress of diagnostic techniques and have not previously been described in the literature, are characterized by multilocular cysts with papillary proliferation of the lining epithelium. They occur exclusively in the head and body, predominantly in males, and coexistence of well-differentiated adenocarcinoma as well as adenoma components is frequently encountered. These lesions are quite different from hitherto described mucinous cystic neoplasms of pancreas, not only in terms of gross features but also with regard to intrapancreatic location, and sex and age distributions. We propose to classify these lesions as a new pancreatic tumor entity: the ductectatic-type mucinous cystadenoma/cystadenocarcinoma. PMID- 8514616 TI - The effect of aging on the seminiferous epithelium of the brown Norway rat. AB - Aging of the mammalian testis is often accompanied by loss of germ cells and, as a result, decreased daily sperm production. It is currently unknown whether cell loss is the result of aging-related changes in germ cells or whether there are also aging-related changes in the Sertoli cells that normally support germ development and differentiation. To begin to compare the effects of age on germ cells and on Sertoli cells, we examined brown Norway rats of 6, 12, 18, 21, and 24 months of age for the frequency of seminiferous tubule regression and total testis contents of transcripts for three Sertoli cell products: SGP-2, transferrin, and cyclic protein-2 (CP-2)/cathepsin L. Histological analysis revealed no changes in the seminiferous epithelium from 6 to 12 months of age. However, from 12 to 24 months of age, the percentage of normal tubules gradually decreased from 95% to 15% of the total while the percentage of fully regressed tubules (containing no germ cells per tubule cross section) increased from 0% to 78%. In our analysis of specific Sertoli cell transcripts, we noted no change in total testis content of SGP-2 mRNA from 6 to 24 months. However, total testis content of transferrin mRNA was unchanged from 6 to 18 months, but increased by 24 months to 368% of the content of a 6-month-old testis. In contrast, total testis content of CP-2/cathepsin L mRNA was unchanged from 6 to 12 months, but decreased by 24 months to 58% of the content of a 6-month-old testis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514617 TI - Testicular steroidogenesis in the aging brown Norway rat. AB - In seeking an animal model of age-associated changes in the male reproductive tract, we examined the effects of age on the health and testicular steroidogenic activity of the Brown Norway rat, with comparisons made to the Sprague-Dawley rat. When perfused in vitro under conditions of maximally stimulating luteinizing hormone significant age-associated reductions were seen in testosterone production by testes of Sprague-Dawley rats of 21-24 months of age and by testes of Brown Norway rats of 18-30 months of age. Decreases in the capacity of the testes to produce testosterone were reflected in age-associated decreases in both serum testosterone and in testosterone concentration within the seminiferous tubule fluid. In contrast to the Sprague-Dawley rat, changes in steroidogenic activity in the Brown Norway rat were not accompanied by the occurrence of pituitary adenomas, obesity, or testicular tumors. This along with its longevity, make the Brown Norway strain a highly promising model for testicular aging. PMID- 8514618 TI - Validation of an improved in vitro bioassay to measure LH in diverse species. AB - Cultured Leydig tumor cells (MA-10) respond to luteinizing hormone (LH) by synthesizing and secreting progesterone (P). The specificity of the response to LH prompted us to develop this system for use as a simple and rapid in vitro bioassay for LH. The aims of this study were to (1) improve sensitivity and reproducibility, and (2) optimize the assay for use in diverse animal species. A minimum sensitivity was observed at 0.05 mlU/well of LH with 0.5 x 10(4) cells/well for 1.5 hours. At higher concentrations of LH, shorter incubation periods also significantly stimulated P production. Addition of human LH standard or serum samples resulted in a dose-dependent increase in P production. Parallel dose-dependent curves were observed with LH preparations from mammalian, avian, and amphibian species. In conclusion, these findings demonstrate that (1) the assay is rapid, sensitive, and reproducible; (2) serum LH levels analyzed using this assay and the mouse Leydig cell bioassay are comparable; (3) shorter incubation times suggest the implementation of this assay for rapid qualitative determination of LH surges; and (4) the assay can be used for the analysis of samples from diverse species, especially those lacking radioimmunoassays. Therefore, this assay system allows for the simple and rapid measurement of circulating bioactive LH levels in humans and diverse animal species, and should provide insight regarding the role of bioactive LH in physiological and pathological conditions. PMID- 8514619 TI - Analysis of the responses of human spermatozoa to A23187 employing a novel technique for assessing the acrosome reaction. AB - Protocols for the use of A23187 in assessing the ability of human spermatozoa to acrosome-react and exhibit sperm-oocyte fusion have been developed and the results compared in two independent cohorts of infertile patients. Both bioassays were found to depend upon such factors as the dose and formulation of A23187, the duration of exposure, and the amount and type of protein used to supplement the medium. An optimal protocol for the hamster oocyte penetration test comprised a 3 hour exposure to 1.25-2.5 microM ionophore and gave penetration rates of 93.2 +/- 3.2% (11.26 +/- 1.27 sperm/egg) for a group of 33 fertile donors compared with 63.0 +/- 5.4% (4.73 +/- 0.81 sperm/egg) for a cohort of 56 patients consulting for infertility (P < 0.001). Higher doses (5.0-10.0 microM) of A23187 caused an inhibition of sperm-oocyte fusion in association with a loss of motility, although the integrity of sperm plasma membrane did not appear to be compromised and high rates (approximately 80%) of acrosome reaction were observed. A protocol for assessing the ability of viable human spermatozoa to acrosome-react in response to A23187 was developed, employing a fluorescein-conjugated lectin in concert with the hypoosmotic swelling test, which gave values of 20.1 +/- 2.6% and 13.6 +/- 1.6% for groups of fertile donors (n = 29) and infertile patients (n = 32) respectively (P < 0.05). Although only acrosome-reacted spermatozoa were capable of fusing with zona-free hamster oocytes, there was no significant correlation between the proportion of acrosome-reacted cells and the levels of sperm-oocyte fusion observed in two independent groups of patients, indicating that these bioassays are measuring different aspects of human sperm function. These results have implications for the way in which the responses of human spermatozoa to ionophore treatment are quantified and interpreted. PMID- 8514620 TI - Column separation of motile sperm from stallion semen. AB - Subfertility in stallions is common, and methodologies are needed to increase the fertility in these animals. In other species, removal of the dead sperm from semen increases the quality and fertility of semen. With horse semen we evaluated 48 combinations of column separation techniques using micro-spin chromatography columns. The greatest improvement in motility was observed with glass wool, whereas glass beads exhibited the greatest recovery of motile sperm. Although centrifugation time did not influence recovery rate or percent motility, a column length of 2 cm was superior for recovery of motile sperm. In scale-up experiments using 2-cm columns of glass beads in 50-ml syringe barrels, centrifugation proved to be superior to gravity flow, suction, and syringe plunger as extraction methods for drawing semen through the column; however, gravity flow produced acceptable results and may be more suitable for use in a field setting. When the volume of semen for separation was increased from 10 ml to 20 ml, the recovery rate of motile sperm was also increased. Further increasing the volume of semen for separation did not improve the recovery rate, and for volumes greater than 50 ml the column had a tendency to "clog." Thus, a suitable method for column separation of equine sperm utilizes a 2-cm column of glass beads in a 50-ml syringe casing. Centrifugation is the ideal extraction method; however, gravity flow is an acceptable extraction method suited to the field setting, using a maximum semen volume of 50 ml. PMID- 8514621 TI - The postcoital test: a quantitative method. AB - A minor modification of the postcoital test (PCT) is made, which allows for a volumetric inspection of the cervical mucus with a standard clinical microscope. Homogeneously sized (40.3-microns) plastic microspheres are sprayed on the cervical mucus prior to placement of the coverslip, and these act as spacers to keep the slide-to-coverslip distance constant. As a result a known volume of cervical mucus is inspected with each microscope field of view and actual sperm concentrations can be calculated. Results from 20 patients are presented. Postcoital mucus samples were analyzed with and without spacer particles. Much of the variability in the microscopic portion (sperm concentration and motility) of the PCT test seems to be attributable to a factor controlled by the microparticles, presumably slide-to-coverslip distance. Variability in both sperm density and motility is decreased by the application of the microspheres. PMID- 8514622 TI - Insulin-like growth factor 1, but not growth hormone, has in vitro proliferative effects on neonatal foreskin fibroblasts without affecting 5-alpha-reductase or androgen receptor activity. AB - Clinical observation of patients with congenital growth hormone (GH) deficiency and Laron-type dwarfism suggests that factors such as GH or insulin-like growth factor 1 (IGF-1) might in addition to androgens, be needed for normal phallic growth. We speculated GH or IGF-1 might have direct actions on genital tissues and performed the present study to evaluate the in vitro effects of GH and IGF-1 on cultured neonatal foreskin fibroblasts. Cells derived from foreskins of normal newborns were studied between cell passages 6 and 15. Serum-free media with and without 100 ng/ml GH, IGF-1, or both were added 24 hours prior to and at the time of study. To determine the activity of 5-alpha-reductase (5-alpha-R), 3H testosterone (T: 2 nM) was added, and 5-alpha-R activity was calculated as femtomoles 3H-dihydrotestosterone and 3H-androstanediol produced/microgram DNA/hour. Androgen receptor (AR) binding was determined by the addition of 3H dihydrotestosterone (dHT; 0.03125-0.5 nM) in the presence and absence of a 200 fold excess of unlabeled dHT. Specific binding was used in Scatchard analysis for determination of AR number (Bmax) and binding affinity (Kd). The rate of DNA synthesis was determined by incorporation of 3H-thymidine (3H-Thy) into trichloroacetic acid-insoluble material. DNA and protein content were determined on cell lysates. IGF-1, but not GH, had proliferative effects (significant increases in the rate of 3H-Thy incorporation, DNA, and protein content) but no effect on 5-alpha-R activity, Bmax or Kd.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514623 TI - Germ cell-conditioned medium contains multiple factors that modulate the secretion of testins, clusterin, and transferrin by Sertoli cells. AB - In view of the evidence showing that germ cells regulate Sertoli cell (SC) function, the aim of this study was to examine if germ cell (GC)-conditioned media contained multiple biological factors that affect SC secretory functions. Total GC were isolated from adult rat testes. Pachytene spermatocytes (SPC) and early spermatids (SPT) were enriched to about 90% pure by centrifugal elutriation. GC, SPC, and SPT were cultured in serum-free medium for 20 hours with a viability greater than 95%. Conditioned media derived from these cells were fractionated by anion-exchange high-performance liquid chromatography (HPLC). An aliquot from each of these fractions was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and proteins were visualized by silver staining. The patterns of protein staining using media from GC, SPC, and SPT were similar. Bioassays of these column fractions on SC showed that the transferrin stimulatory, the testins inhibitory, and the clusterin inhibitory activities were eluted from the anion-exchange HPLC column in overlapping fractions. To determine whether these activities were confined to one or several molecules, further fractionations were performed. Eleven liters of GC-conditioned medium were fractionated by sequential HPLC using anion-exchange, gel permeation, and reversed-phase columns. Throughout the entire fractionation scheme, the HPLC fractions were bioassayed using primary SC-enriched cultures prepared from 20-day old rats by incubating SC with aliquots of these fractions for 24 hours to monitor their effects on SC secretory function. The concentrations of transferrin, clusterin, and testins were quantified by specific radioimmunoassays. These studies showed that the transferrin stimulatory activity can be fractionated into four peaks (I, IIa, IIb, and IIc); clusterin inhibitory activity into three peaks (A, B, and C); and testins inhibitory activity into two peaks (1 and 2). Some of these bioactivities were eluted in overlapping fractions such as I and B, IIb and 1, and IIc and 2, whereas A, C, and IIa were not associated with any other assayed activities. In summary, additional GC modulators of SC function were identified for the first time, these include clusterin and testins inhibitors. The previously identified transferrin stimulatory activity was also resolved into multiple molecular forms. PMID- 8514624 TI - 5-Hydroxyanthranilic acid derivatives as potent 5-lipoxygenase inhibitors. AB - Three new 5-lipoxygenase inhibitors, designated as BU-4601 A, B and C, were found in the fermentation broth of Streptomyces sp. strain No. AA2807. Their structures were identified as isodecyl, isoundecyl and isolauryl esters of 5 hydroxyanthranilic acid, respectively. Based on their structures, five related esters were synthesized and evaluated for biological activity as inhibitors of 5 lipoxygenase. Both naturally-occurring and chemically-synthesized compounds exhibited almost equal levels of 5-lipoxygenase inhibitory activities in vitro. PMID- 8514625 TI - Benastatins C and D, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. Production, isolation, structure determination and biological activities. AB - Benastatin C, a new member of the benastatins, has been isolated from the culture broth of Streptomyces sp. MI384-DF12. The structure of benastatin C was elucidated as 2-decarboxy-benastatin A by NMR studies. Benastatin D, 2 decarboxybenastatin B, was derived from benastatin B. Benastatins C and D showed inhibitory activities against human pi class glutathione S-transferase (GST pi) and excellent stimulatory activities on the murine lymphocyte blastogenesis in vitro. PMID- 8514626 TI - Leptolstatin from Streptomyces sp. SAM1595, a new gap phase-specific inhibitor of the mammalian cell cycle. I. Screening, taxonomy, purification and biological activities. AB - Leptolstatin, a new inhibitor of the progression of G1 and G2 phases of the mammalian cell cycle, was discovered through a unique screening system, in which effects of microbial metabolites on the cell cycle progression of the cultured rat fibroblasts were monitored by flow cytometry. The new inhibitor was extracted from the fermentation broth of Streptomyces sp. SAM1595 with ethyl acetate, and purified by silica gel column chromatography and HPLC. Leptolstatin showed a strong cytostatic effect on rat normal fibroblasts 3Y1 with an IC50 value of 0.4 ng/ml, but its antimicrobial activity was very weak. A 24-hour treatment of the fibroblast cells with 10 ng/ml of leptolstatin caused an arrest at G1 or G2 phase, as determined by flow cytometry. When the G2-arrested cells were freed from leptolstatin, those containing 4C DNA entered a new S phase without intervening M phase, resulting in the formation of proliferative tetraploid cells. PMID- 8514627 TI - Leptolstatin from Streptomyces sp. SAM1595, a new gap phase-specific inhibitor of the mammalian cell cycle. II. Physico-chemical properties and structure. AB - Leptolstatin, a product from Streptomyces sp. SAM1595, is a gap phase-specific inhibitor of the mammalian cell cycle. Physico-chemical properties and spectrometric analyses showed that the structure of leptolstatin is (2Z,6E,8Z,12E,14E,22E)-19,24-dihydro xy-8,10,14,16,18,20,22-heptamethyl-17-oxo-2 , 6,8,12,14,22-tetracosahexaen-5-olide. PMID- 8514628 TI - Rhizopodin, a new compound from Myxococcus stipitatus (myxobacteria) causes formation of rhizopodia-like structures in animal cell cultures. Production, isolation, physico-chemical and biological properties. AB - A new cytostatic compound, rhizopodin, was isolated from the culture broth of the myxobacterium, Myxococcus stipitatus. The compound inhibited growth of various animal cell cultures without killing the cells. The ID50, measured by an MTT assay, was 12 approximately 30 ng/ml, depending on the cell line. Especially cells growing fibroblast-like showed typical morphological changes. They became larger and within hour formed long branching and reticular runners. These morphological changes were irreversible. Rhizopodin suppresses bleb formation in K-562 cells, and therefore could act by interacting with protein phosphorylation. PMID- 8514629 TI - Xanthoquinodins, new anticoccidial agents produced by Humicola sp. Production, isolation and physico-chemical and biological properties. AB - Humicola sp. FO-888, a soil isolate, was found to produce a series of new anticoccidial compounds. Five active compounds, designated xanthoquinodins A1, A2, A3, B1 and B2 were isolated from the fermentation broth of the producing strain by solvent extraction and HPLC. Xanthoquinodins inhibited the growth of Eimeria tenella in an in vitro assay system using BHK-21 cells as a host. No schizont in the cells was observed at concentrations of 0.02-0.2 micrograms/ml for xanthoquinodins A1, A3, B1 and B2 and at 0.02 micrograms/ml for xanthoquinodin A2. PMID- 8514630 TI - Diolmycins, new anticoccidial agents produced by Streptomyces sp. I. Production, isolation and physico-chemical and biological properties. AB - Streptomyces sp. WK-2955, a soil isolate, was found to produce a series of new anticoccidial compounds. Four active compounds, designated diolmycins A1, A2, B1 and B2, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, gel filtration on Sephadex LH-20, and preparative HPLC. Diolmycins inhibited the growth of Eimeria tenella in an in vitro assay system using BHK-21 cells as a host. No schizont in the cells was observed at concentrations of 0.02-2.0 micrograms/ml for diolmycin A1, at 0.2-2.0 micrograms/ml for diolmycin A2, and at 20 micrograms/ml for diolmycins B1 and B2. PMID- 8514631 TI - Diolmycins, new anticoccidial agents produced by Streptomyces sp. II. Structure elucidation of diolmycins A1, A2, B1 and B2, and synthesis of diolmycin A1. AB - The structures of diolmycins A1, A2, B1 and B2, novel anticoccidial agents, were determined by spectroscopic analyses. Diolmycins A1 and A2 are stereoisomers with the structure of 1-(3-indolyl)-4-(p-hydroxyphenyl)-2,3-butanediol. From the chemical synthesis of the erythro-isomer, the relative configurations of diolmycins A1 and A2 were determined to be the erythro- and threo-isomers, respectively. The stereoisomers, diolmycins B1 and B2, were also deduced to be erythro- and threo-1,4-di-(p-hydroxyphenyl)-2,3-butanediol, respectively. PMID- 8514632 TI - CL307-24, a new antibiotic complex from Saccharopolyspora aurantiaca sp. nov. I. Taxonomy, fermentation and purification. AB - CL307-24, a complex of new antibiotics has been isolated from the fermentation broth of Saccharopolyspora aurantiaca sp. nov. The complex was purified by cation exchange and hydrophobic interaction chromatographies. It was then resolved as one major and three minor components by silica gel chromatography and HPLC. PMID- 8514633 TI - Amphotericin B-induced resistance to Pseudomonas aeruginosa infection in mice. AB - We evaluated the effects of amphotericin B (AmB) against Pseudomonas aeruginosa (P. aeruginosa) infection in mice. Pretreatment with 2 mg/kg of AmB 24 hours before infection significantly increased the survival rates of mice intraperitoneally infected with either P. aeruginosa or Escherichia coli. To evaluate the mechanism of this AmB-induced resistance to infection, we conducted a number of experiments. Peritoneal macrophages exposed in vitro to AmB showed superior bactericidal activity compared to that of control macrophages. Interleukin-1 production by peritoneal macrophages from mice pretreated with 2 mg/kg of AmB was significantly higher than that in control mice. Serum tumor necrosis factor level after intravenous injection of P. aeruginosa was also higher in mice pretreated with 2 mg/kg of AmB than in control mice. These data indicate that AmB induces resistance to P. aeruginosa in mice. Furthermore AmB induced activation of peritoneal macrophages and their production of interleukin 1 and tumor necrosis factor appeared to play important roles in this phenomenon. PMID- 8514634 TI - Conformation studies on and assessment by spectral analysis of the protein chromophore interaction of the macromolecular antitumor antibiotic C-1027. AB - Characterization of the secondary structure of the antitumor antibiotic C-1027 has been made from a comparison of C-1027 and its apoprotein by various analytical means. The results indicated the antibiotic to be abundant in beta structure by measurements of Fourier-transform infrared (FT-IR) spectroscopy and the circular dichroism (CD) spectrum, and by a prediction of the secondary structure based on the amino acid sequence of the peptide. In comparison of the IR spectra of their proteins in D2O, the apoprotein exhibited a faster H-D exchange than C-1027, indicating an increase in the "non-motile parts" of the beta-sheets formed through the protein-chromophore interaction in holo-C-1027. The prediction of hydropathic index indicated the hydrophobic residues of the apoprotein to be predominantly located in the beta-sheet structures, suggesting hydrophobic interaction in the binding between chromophore and apoprotein. Further, the interaction between chromophore and apoprotein was detected by a fluorescence method. The result showed the dissociation constant (Kd) to be 6.88 x 10(-5) M, indicating that the chromophore is tightly bound to the protein moiety. PMID- 8514635 TI - Synthesis and antimicrobial activity of sperabillin derivatives. AB - Modification of sperabillins was carried out. The 2-amidinoethylamino moiety was removed by brief acidic hydrolysis. The 2,4-hexadienoyl moiety was hydrogenated to the hexanoyl moiety and this was cleaved by an enzymatic reaction using the cells of Pseudomonas acidovorans IFO 13582. The 2-amidinoethylamino and the 2,4 hexadienoyl moieties were replaced with other groups. The derivative which was prepared by condensation of two molar amounts of dehexadienoylsperabillin A with (E,E)-muconic acid showed better protective effects than sperabillin A against Gram-negative bacteria. PMID- 8514636 TI - Synthetic studies of erythromycin derivatives. Synthesis and antimicrobial activities of 3''-EPI-erythromycin A and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11- oxoerythromycin A. AB - Two new derivatives, 3''-epi-erythromycin A (2) and (9S)-11-dehydroxy-9-deoxo-9 hydroxy-11-oxoerythromycin A (3), have been synthesized by using glycosylation with glycal (Ferrier rearrangement), bromomethoxylation and bis(tributyltin) oxide-bromine oxidation as the key steps. Their antimicrobial activities were compared with those of erythromycin A (1). PMID- 8514637 TI - Studies on the structures of meropenem(SM-7338) and it's primary metabolite. AB - The structure and solution conformation of meropenem was examined by using 1H and 13C NMR spectroscopy and nuclear Overhauser enhancement experiments. Similar to the X-ray crystal structure, the close spacing of 1 beta-methyl substituent to the beta-lactam ring and the accessible conformation of C-2 side chain in relation to the carbapenem skeleton was confirmed. The structure of the primary metabolite of meropenem by dehydropeptidase-I was shown to be the beta-lactam ring-opened product by comparing the spectroscopic data with those of meropenem, and confirmed by the preparation and structural analysis of its crystalline derivative. This metabolite existed as a mixture of 1-pyrroline and 2-pyrroline isomers, and the coexistence of two isomers at equilibrium in aqueous solution was observed by NMR. PMID- 8514638 TI - Synthesis and antibacterial activity of cephalosporins having a catechol in the C3 side chain. AB - Cephalosporins having a catechol through a variety of linkages to the C3 position and a different C7 side chain were prepared. Among them, 3-(catechol-4- ylcarbonyloxy)methylcephalosporin (14) and 3-[(E)-3-(catechol-4-ylcarbonyloxy)-1 propen-1-yl]cephalospo rin (10) showed excellent activity against Gram-negative activity including ceftazidime-resistant Escherichia coli, Pseudomonas aeruginosa, Xanthomonas maltophilia and Pseudomonas cepacia. PMID- 8514639 TI - Cephalosporins having a heterocyclic catechol in the C3 side chain. I. Enhancement of efficacy against gram-negative bacteria. AB - Two groups of cephalosporins substituted with a variety of heterocyclic catechols in the C3 side chain were synthesized. One is a group of 3-(heterocyclic catechol substituted methyl)cephalosporins and another is 3-[(E)-3-heterocyclic catechol substituted 1-propen-1-yl]cephalosporins. Cephalosporins in the latter group showed higher in vivo efficacies than those in the former group having the same heterocyclic catechol, especially against Pseudomonas aeruginosa A9843A, although there was no significant difference between their in vitro activity. Among the latter group, the 5,6-dihydroxybenzimidazole derivative (6e) and the 2,6-dihydro 7-hydroxy-6-oxo- isoquinoline derivative (6b) showed much higher activity than ceftazidime (CAZ) and imipenem (IPM) against P. aeruginosa A9843A both in in vitro and in vivo studies. PMID- 8514640 TI - Cephalosporins having a heterocyclic catechol in the C3 side chain. II. Improvement of pharmacokinetic profile. AB - 7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3- [propen 1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity. PMID- 8514641 TI - WS1279, a novel lipopeptide isolated from Streptomyces willmorei. Fermentation, isolation and physico-chemical properties. PMID- 8514642 TI - Sch 47554 and Sch 47555, two novel antifungal antibiotics produced from a Streptomyces sp. PMID- 8514643 TI - Production of a novel polyketide antibiotic, jadomycin B, by Streptomyces venezuelae following heat shock. PMID- 8514644 TI - Resistance of yeasts to azole-derivative antifungals. AB - There are relatively few antifungal agents available for the treatment of systemic mycoses. The incidence of these infections, particularly among the immunocompromised, has increased significantly in recent years. Amphotericin B, flucytosine and the azole-derivatives--fluconazole, itraconazole and ketoconazole -are the only drugs of value in the treatment of systemic yeast infections currently available. To date resistance among individual yeast species or strains has only been a serious problem with flucytosine. However, resistance among Candida spp. to orally administered azole-derivatives has been observed. The frequency with which resistance has been described in clinical practice among yeasts differs considerably between the three azole antifungal agents. Fluconazole has been implicated in emergent resistance more frequently than ketoconazole, and ketoconazole more often than itraconazole. It must be a matter for concern that, by analogy with the known emergence of antibiotic-resistance among bacteria, that the widespread use of a drug inactive against a particular species may lead to an increased incidence of such infections. An international epidemiological survey is required to establish the extent and degree of resistance to the azole antifungals. PMID- 8514645 TI - Activity of the beta-lactamase inhibitor BRL 42715 against cephalosporinases produced by Enterobacteriaceae. AB - BRL 42715, a novel beta-lactamase inhibitor, was evaluated for its capacity to inhibit cephalosporinases. BRL 42715 was effective in potentiating the activity of antibiotics against clinical isolates of Enterobacteriaceae that produced high levels of cephalosporinases. This correlated well with the very low 50% inhibition values (< 0.004 mg/L) of BRL 42715 for cephalosporinases extracted from different species. When compared in vitro to clavulanic acid, sulbactam, and tazobactam, BRL 42715 was the most efficient inhibitor of cephalosporinase. PMID- 8514646 TI - Effects of betaines and urine on the antibacterial activity of aminoglycosides. AB - Urine has long been known to inhibit the activity of aminoglycosides against urinary tract pathogens. Glycine betaine which is present in urine confers resistance against high osmolarity to Gram-negative organisms. We postulated that glycine betaine might contribute to the aminoglycoside resistance found in hypertonic urine. Escherichia coli became extremely resistant to gentamicin (40 x MIC in 0.9 M sodium chloride) when cultured in minimal medium supplemented with 10(-4) M glycine betaine and 0.1-1.0 M sodium chloride. Resistance was increased in the presence of high glucose concentrations but to a lesser extent (3 x MIC in 1.0 M glucose). This effect was not produced by other polyols or urea. These results suggest the observed synergism is mediated by the osmoprotective effects of glycine betaine and the inhibitory effect of sodium chloride or glucose against the aminoglycoside. Other betaines tested had a less marked effect. The betaines in urine permit the expression of increased resistance to aminoglycosides in concentrated urine. PMID- 8514647 TI - P-nitrophenylglycerol in susceptibility testing media alters the MICs of antimicrobials for Pseudomonas aeruginosa. AB - Diagnostic microbiology laboratories in Australia and the UK commonly incorporate p-nitrophenylglycerol (PNPG) into solid susceptibility testing media in order to prevent the swarming of Proteus spp. We have investigated the effects of PNPG and adjusting the cation concentrations of the media to physiological levels on the MICs of aminoglycosides and other antibiotics for 128 strains of Pseudomonas aeruginosa isolated from the sputa of children with cystic fibrosis. The addition of PNPG to the media led to higher MICs of gentamicin and tobramycin for up to 23% of the isolates. Depending on the base medium, supplementation with the cations, calcium and magnesium, also increased the MICs of these aminoglycosides for 12-27% of the strains tested. Both incorporation of PNPG and cation adjustment led to higher MICs for 25-53% of isolates, again depending on the base medium. The MICs of ticarcillin, ciprofloxacin and colistin (on Iso-Sensitest agar) for significant numbers of strains were lower in the presence of PNPG, while those of ceftazidime varied from higher to lower, according to the concentration of the drug and the base medium. In many instances these changes would have altered the way in which the susceptibilities of the organisms would have been reported. PNPG clearly exerts an important effect when the in-vitro activities of various antibiotics against P. aeruginosa are determined by the agar dilution method. Recommendations for the inclusion of PNPG in susceptibility testing media should therefore be reviewed. PMID- 8514648 TI - Synergic activity of imipenem/cilastatin combined with cefotiam against methicillin-resistant Staphylococcus aureus. AB - The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia model. Combinations of imipenem plus cefotiam in ratios from 1:5 to 1:160 were more effective than either imipenem alone or cefotiam alone (P < 0.05). Synergy was observed against both beta-lactamase producing and beta-lactamase non-producing MRSA. Staggered combinations of imipenem with cefotiam (each drug was administered at a different time) were studied in an in vitro pharmacokinetic system to clarify relationships between killing kinetics and pharmacodynamics of the combinations. In the in-vitro system, cefotiam (1 g over 30 min) administered 2 h after imipenem administration (250 mg over 30 min) reduced viable cell counts to an undetectable level and maintained this for 4 h, while the simultaneous administration of imipenem and cefotiam maintained an undetectable cell count for only 2 h. Furthermore, imipenem administered after cefotiam showed no synergy. These results indicate that the timing of dosing of each antibiotic influences synergy, and administration of cefotiam 2 h after imipenem is more effective than the other regimens. PMID- 8514649 TI - An eight-year survey of the antimicrobial susceptibility patterns of 85,971 bacteria isolated from patients in a district general hospital and the local community. AB - Antimicrobial susceptibilities were determined for 85,971 bacteria isolated from clinical specimens in the microbiology department of a single district general hospital during the eight-year period between 1984 and 1991. The isolates included 45,786 coliforms, 4483 Proteus spp. and 2644 Pseudomonas spp. from urine and 13,324 Staphylococcus aureus, 7311 beta-haemolytic streptococci, 4741 coliforms, 3643 Pseudomonas spp., 2778 Haemophilus influenzae, 638 Proteus spp. and 623 Streptococcus pneumoniae from other sites (excluding blood). Patterns of susceptibility remained largely unchanged during the study period, except for a decline in the susceptibility of Proteus spp. to trimethoprim between 1984 and 1988 which had reversed itself by 1990 and a reduction in the susceptibilities of Pseudomonas spp. and S. aureus to ciprofloxacin between 1986 and 1991. The susceptibilities of coliforms which had been isolated from sites other than the urinary tract to ampicillin, cefazolin and cefuroxime decreased between 1984 and 1988 but a more variable pattern was noted in subsequent years. Susceptibility of S. aureus to penicillin fell during the first five years of the study but has remained stable since. No change was observed in the susceptibility pattern of H. influenzae. In our experience, gentimicin-resistant Gram-negative bacilli, methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were rarely isolated. PMID- 8514650 TI - Enhanced Staphylococcus aureus susceptibility to immunodefences induced by sub inhibitory and bactericidal concentrations of imipenem. AB - Recent evidence suggests that the selection of an antibiotic for the treatment of infection should take into account not only the drug's antimicrobial activity but also the way in which it interacts with host defence mechanisms, since this may influence the response to infection. In this study we have investigated the effects of imipenem on the activities of human macrophages against Staphylococcus aureus. Bacterial susceptibility to phagocytosis and intracellular killing were determined after S. aureus and macrophages were incubated both simultaneously with sub-inhibitory and bactericidal concentrations of imipenem and following pre exposure of the organisms and the macrophages individually to the same concentrations of imipenem. At both concentrations and under both circumstances, imipenem potentiated the phagocytic and microbicidal activities of the macrophages. PMID- 8514651 TI - Liposomal hamycin in the control of experimental aspergillosis in mice: effect of phosphatidic acid with and without cholesterol. AB - Hamycin incorporated into liposomes containing phosphatidylcholine (SPC) and phosphatidic acid (PA) had reduced toxicity and an enhanced antifungal activity in experimental aspergillosis in balb/c mice. Incorporation of cholesterol into liposomes led to a dose dependent decrease in the toxicity of hamycin. The LD50 (mg/kg) of hamycin contained in SPC/cholesterol/PA (molar ratio 4:5:1) liposomes was 2.8 whereas that in SPC/PA liposomes (molar ratio 9:1) was 0.35. Although the free drug had little or no protective effect on the animals, those administered liposomal hamycin at an equivalent dose (0.1 mg/kg) in the absence of cholesterol (SPC/PA; molar ratio 9:1) showed 90% survival after seven days of therapy. On the other hand the presence of cholesterol in the carrier phosphatidic acid liposomes (SPC/cholesterol/PA; molar ratio 4:5:1) at a similar dose (0.1 mg/kg) led to a 60% survival over the same time period. Hamycin incorporation in phosphatidic acid liposomes both in the presence or absence of cholesterol was found to be effective in reducing the fungal load in lung, liver, spleen and kidney. Studies with distribution of hamycin in various tissues by HPLC showed a significant reduction in the concentration of the liposomal drug in circulation as compared to those seem after administration of free drug. PMID- 8514652 TI - Tissue penetration of clindamycin in diabetic foot infections. AB - Serum and tissue samples were obtained during surgery from four diabetics with neuropathy who underwent debridement or amputation for foot infections while receiving clindamycin 600 or 900 mg iv. Clindamycin concentrations were assayed by radioimmunoassay. Clindamycin was detected in all serum and tissue samples (range: 0.04-2.8 mg/kg in tissues and 1.1-11.1 mg/L in serum). In nine of the eleven tissue samples the clindamycin concentration exceeded the MICs reported for many pathogens commonly involved in such infections. In only a single instance was the ratio of tissue to serum concentration < 0.13. PMID- 8514653 TI - Once-daily versus thrice-daily dosing of netilmicin in combination with beta lactam antibiotics as empirical therapy for febrile neutropenic patients. AB - In a prospective, randomized trial, netilmicin given once daily (OD) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen (TD), both in combination with a broad spectrum beta-lactam, as initial empirical therapy for febrile neutropenic patients; the total daily dosage of netilmicin in each group was 6 mg/kg body weight. Twenty-nine of the 116 (25%) evaluable patients had microbiologically documented septicaemia, most of which were caused by Gram-positive bacteria, 41 (35%) had microbiologically documented infection without bacteraemia and 46 (40%) had possible infection. Highest peak serum concentrations of netilmicin in the OD group were significantly higher and trough serum concentrations significantly lower than in the TD group. A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome. The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy. Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment. The incidence of nephrotoxicity was low and did not differ significantly between groups. Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing, but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy. PMID- 8514654 TI - Audit of prescription and assay of aminoglycosides in a UK teaching hospital. AB - Despite potential nephrotoxicity and ototoxicity, aminoglycosides are widely used in the treatment of severe sepsis but monitoring of serum levels is necessary. The use and assay of aminoglycosides, together with microbiologists' and pharmacists' advice on dosage and potential toxicity were examined in a teaching hospital group during an eight week period. A total of 480 courses of aminoglycoside was recorded in 440 hospital in-patients and of these, 306 (64%) were for prophylaxis. For 79 (45%) of 174 therapeutic courses, bacteriological results were available at the start and the choice of antibiotic was appropriate in 69 cases. Serum aminoglycoside assays were performed in 86% (149/174) of therapeutic courses. Correct assay request forms were used in 79% of 473 assay requests, and the clinical diagnosis was given on 73% of forms. In so-called peak samples with a documented time of collection, this ranged from 5 min to over 9 h post dose. Potentially toxic concentrations were present in 56 (12%) serum samples from 50 courses, in ten of which there was a serum creatinine rise of > 40 microM. However, there were confounding factors in five cases. Probable nephrotoxicity was rare, although assays were not performed in 14% of therapeutic courses. There were no symptomatic cases of ototoxicity but audiometry and vestibular studies were not performed. Closer liaison between the microbiologists, pharmacists and clinical staff is essential to improve clinical practice. Computer notification of inadequately monitored courses would be helpful. The routine therapeutic use of aminoglycosides needs to be reviewed in the light of the rising costs of assay litigation and the increasing number of alternative antibiotics available. PMID- 8514655 TI - The box-plot method for illustrating MIC data. PMID- 8514656 TI - Achieving bactericidal therapy and high-level aminoglycoside resistance. PMID- 8514657 TI - Susceptibility of resistant Enterococcus faecium to unusual antibiotics. PMID- 8514658 TI - The antibacterial activity of co-amoxiclav. PMID- 8514659 TI - Inactivation of imipenem by faecal fractions from human volunteers and the effect of clavulanate and cilastatin. PMID- 8514660 TI - Airway occlusion pressure. AB - Airway occlusion pressure has been used in the past two decades for assessing output of the respiratory controller. It gives a measurement of a weighted sum of the effect of all respiratory muscles active at a given time and, unlike ventilation or tidal volume, does not depend on the resistance or compliance of the respiratory system. In anesthetized subjects or animals, it gives a tracing of the time course of respiratory neuromuscular output through the respiratory cycle, modified by elimination of most phasic vagal stretch receptor feedback and perhaps slightly by activation of some chest wall reflexes. The original postulate that an occluded inspiration would be isometric and the measured pressure free from losses due to force-length and force-velocity has been shown to be incorrect. The volume at which occlusion takes effect, distortions of the chest wall during the maneuver, tonic vagal input, and strength of the muscles must be taken into account when the data are interpreted. Brief occlusions [pressure at 0.1 s (P0.1)] are useful in measuring output in the very first part of inspiration in conscious subjects but must be treated with a great deal of caution. They are most reliable when end-expiratory volume remains constant and there are no important phase lags between flow and pressure. Allowance may be necessary for damping of the pressure signal on its passing through the compliant upper airway. Changes in P0.1 may often be due to changes in the shape of the driving pressure wave without a proportionate change in overall output. The technique remains useful when its limitations are recognized. Because of its simplicity, it can be easily and usefully applied to a range of clinical investigations. PMID- 8514661 TI - Early and late respiratory-related cortical potentials evoked by pressure pulse stimuli in humans. AB - Although respiratory-related cortical evoked potentials (CEPs) have been obtained in humans, early-latency responses have been obtained only with direct electrical stimulation of respiratory afferents. We have recorded both early and late cortical activity in response to a relatively novel stimulus consisting of a 300 ms negative pressure pulse applied to the mouth near the start of selected inspirations, when mouth pressure attained a predetermined threshold. This stimulus caused highly reproducible and rapid changes in mouth pressure and was effective in eliciting CEPs to a wide range of applied pressures. Using pulses of approximately -2 to -25 cmH2O, we obtained an early positive component with a mean latency of approximately 20 ms and a subsequent negative component at approximately 30 ms in normal subjects. Peak-to-peak amplitude varied directly, and component latencies inversely, as a function of pulse magnitude. Using -5- to -10-cmH2O stimuli, we also measured a later positive-negative-positive response with mean component latencies of 96.7 +/- 15.1, 147 +/- 14.8, and 237.6 +/- 23.5 ms, respectively. The early-latency activity was resistant to manipulations of stimulus predictability, whereas the later waves were attenuated or disappeared when load presentation was made completely predictable. We validated our method by eliminating the possibility of tactile stimulation of the lips and teeth as the origin of the evoked responses. We propose that early-latency activity derives from precortical structures and may provide a window on the functioning of respiratory afferents in normal subjects and in patients with respiratory disease. PMID- 8514662 TI - Blood flow elevation increases VO2 maximum during repetitive tetanic contractions of dog muscle in situ. AB - Blood flow through the gastrocnemius-plantaris muscle of the dog in situ was increased by a pump in the arterial supply during a 30-min period of 1/s isotonic tetanic contractions. Compared with a control series of experiments with normoxemia and spontaneous flow, the pump increased flow 84%, from 1.51 +/- 0.08 to 2.78 +/- 0.15 ml.g-1.min-1. The perfusion pressure was increased from 125 to 196 mmHg. The pump hyperemia increased maximal O2 uptake (VO2) at 5 min of contractions by 31%, from 8.97 +/- 0.44 to 12.89 +/- 0.30 mumol.g-1.min-1. The extraction was decreased, and venous PO2 (PVO2) was increased. Fatigue, measured as a drop in power production from the highest level at 10 s to 30 min, was 49% during pump hyperemia and 54% in the control conditions. VO2 decreased 30% from the 5-min value to the 30-min value with pump hyperemia and 28% over the same time in the control conditions. At maximal VO2, the ratio VO2/PVO2 was increased by pump hyperemia compared with control conditions, suggesting an increased O2 diffusing conductance of the muscles. We conclude that the elevated perfusion pressure of pump hyperemia increased flow to raise maximal VO2 mainly in areas of the muscle that had restricted flow under control conditions. PMID- 8514663 TI - Dynamic imaging of the upper airway during respiration in normal subjects. AB - The present study was conducted to determine the effects of quiet respiration on upper airway caliber in 15 normal subjects by using cine computed tomography. The cine computed tomography (Imatron) scanner was programmed to obtain 8-mm-thick axial slices every 0.4 s during inspiration and expiration at four anatomic levels, from the nasopharynx to the retroglossal region. Airflow (pneumotachograph) was measured, and tidal volume was obtained by integration. Upper airway area, determined by an objective edge detection algorithm, was plotted as a function of tidal volume to generate a loop describing upper airway area changes at each level during a respiratory cycle. The results demonstrate a 17% change in airway size across all anatomic levels during respiration. The maximum upper airway cross-sectional area at all four anatomic levels was significantly greater during expiration than during inspiration. Other major findings include 1) upper airway cross-sectional area decreases slightly during early inspiration, enlarges toward end inspiration, and is larger at end inspiration than at the beginning of inspiration; 2) upper airway cross-sectional area enlarges from end inspiration to the first point in expiration; the airway enlarges further, reaching its maximum early in expiration, and then narrows toward end expiration; and 3) the changes in upper airway dimensions during resting tidal breathing are greater in the lateral than in the anteroposterior direction. The data suggest that during inspiration, the action of negative intraluminal pressure may be largely balanced by the action of the upper airway dilator muscles, whereas during expiration, positive intraluminal pressure produces expansion of the upper airway. PMID- 8514664 TI - Oxygen radicals, lipid peroxidation, and permeability changes after intestinal ischemia and reperfusion. AB - This study examined the effects of a 21-aminosteroid, U-74389, on lipid peroxidation [determined by plasma and tissue malondialdehyde (MDA) levels], intestinal permeability (plasma-to-luminal clearance of 51Cr-labeled EDTA), and intestinal blood flow (laser Doppler) during and after intestinal ischemia [superior mesenteric artery (SMA) and collateral vessel occlusion for 20 min with atraumatic clip]. Untreated ischemia increased EDTA clearance (from 0.050 +/- 0.005 to 0.169 +/- 0.040 ml.min-1.100 g-1; n = 16, P = < 0.05), reduced SMA flow 88% (P < 0.05), and increased plasma MDA (0.340 +/- 0.120 to 4.030 +/- 0.86 nmol/ml; n = 8, P = 0.01); 2 h of reperfusion further increased EDTA clearance (0.323 +/- 0.060 ml.mg-1.100 g-1). EDTA clearance remained unchanged from baseline throughout the experimental period in sham ischemic rats (n = 12, 0.060 +/- 0.006 ml.min-1.100 g-1). Aminosteroid treatment at ischemia (n = 10) or with reperfusion (n = 11) returned EDTA clearance to near baseline (baseline 0.071 +/- 0.023; reperfusion 0.091 +/- 0.014 ml.min-1.100 g tissue-1) and reduced the ischemia-reperfusion-associated rise in tissue MDA. Two hours after reperfusion, SMA blood flow was above baseline values in all experimental groups. Our data suggest that oxygen-derived free radicals produced during intestinal ischemia and reperfusion contribute to 1) lipid peroxidation of cell membranes and 2) increases in intestinal mucosal permeability, potentiating bacterial translocation and sepsis. PMID- 8514665 TI - Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation. AB - Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut. PMID- 8514666 TI - Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep. AB - Cardiac function was studied in an unanesthetized ovine model of hyperdynamic endotoxemia. Sixteen sheep were instrumented with ultrasonic crystals on the left ventricle to measure changes in its external diameter, a pressure transducer in the left ventricle, and aortic and Swan-Ganz catheters. The animals received either Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1; LPS group, n = 10] or an equivalent amount of 0.9% NaCl (sham group, n = 6). Between 1 and 8 h after LPS, a hypodynamic state with low cardiac output ensued (LPS 5.0 +/- 0.2 vs. sham 6.3 +/- 0.4 l.min-1.m-2). During this period, the end systolic pressure-diameter relationship, a sensitive index of myocardial contractility, was reduced (LPS 10.4 +/- 1.2 vs. sham 17.2 +/- 0.8 mmHg/mm). After this first phase, the sheep developed a persistent hyperdynamic state characterized by a significant increase in cardiac output. By 24 h after LPS administration, the cardiac output was 10.1 +/- 0.5 l.min-1.m-2 (sham 6.3 +/- 0.3). Despite the marked elevation of cardiac output, the end-systolic pressure diameter relationship had fallen to 8.5 +/- 0.9 mmHg/mm (sham 16.0 +/- 1.2). In a model of hyperdynamic state, an increased cardiac output occurs despite a significant depression in myocardial contractility. PMID- 8514667 TI - Adenosine deaminase and BW A1433U attenuate hypoxia-induced ventricular ectopy. AB - Twenty-six beagles of either sex, weighing 10.4 +/- 0.3 kg, were used to investigate the role of adenosine in the genesis of ventricular arrhythmias during systemic hypoxia. After instrumentation dogs were randomly assigned to one of four treatment groups: 14 dogs were pretreated before hypoxia with adenosine deaminase (n = 7, group I) or its vehicle (n = 7, group II) while 12 other dogs were pretreated with the A1 selective adenosine receptor antagonist BW A1433U (n = 6, group III) or its vehicle (n = 6, group IV). Each dog was exposed to a 3-min period of hypoxic ventilation [3% O2-5% CO2-92% N2; PO2 in arterial blood 96 +/- 3 Torr (before hypoxia), 21 +/- 1 Torr (during hypoxia)]. The percentages of ventricular ectopic beats (19) experienced in the four groups after 3 min of hypoxia were 21 +/- 10% (group I, P < 0.05 relative to group II), 50 +/- 2% (group II), 15 +/- 8% (group III, P < 0.05 relative to group IV), and 42 +/- 7% (group IV). Ventricular bigeminy, the most prominent arrhythmia seen in this study, was significantly reduced by adenosine deaminase and BW A1433U. No significant differences in other monitored cardiovascular variables were seen between adenosine deaminase and BW A1433U treatment groups and their corresponding vehicles. These findings implicate endogenous adenosine as an arrhythmogenic mediator during hypoxia and point to a mechanism involving the A1 adenosine receptor. PMID- 8514668 TI - 31P-NMR spectroscopy of isolated perfused rat lung. AB - We obtained 202.5-MHz 31P-nuclear magnetic resonance (NMR) spectra of isolated perfused rat lungs, degassed and inflated, and of lung extract. The spectra included those of ATP, ADP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters, phosphodiesters, and a broad component due to the membrane phospholipids. The line width at one-half peak height for beta-ATP was 1.0 ppm for the degassed lung and 1.2 ppm for the inflated lung. This suggests that the air-water interfaces in inflated lung, which produce proton NMR line broadening, do not act prominently in 31P-NMR spectroscopy. In a degassed lung, when perfusion was stopped for up to 30 min, PCr and ATP peaks decreased progressively with time while Pi and phosphomonoester peaks increased. On return of flow, these changes reversed. The intracellular pH values calculated from the difference in magnetic field between PCr and Pi peaks of inflated and degassed lungs were 7.16 +/- 0.10 (SD; n = 4) and 6.99 +/- 0.10 (n = 4), respectively. The change of intracellular pH caused by 30 min of ischemia was -0.2 pH units. Our findings indicate that air-water interfaces should not broaden lung 31P peaks in vivo. PMID- 8514669 TI - Aortic baroreflex control of heart rate during hypertensive stimuli: effect of fitness. AB - We examined the aortic baroreflex control of heart rate (HR) in seven healthy young men of average fitness (AF) and seven of high fitness (HF). The fitness level was determined by maximal oxygen uptake (AF = 42.9 +/- 1.1, HF = 62.3 +/- 1.8 ml.kg-1.min-1). Aortic baroreflex control of HR was determined during a steady-state increase of mean arterial pressure (MAP; AF, +15.0 +/- 2.1 and HF, +18.3 +/- 0.8 mmHg) with phenylephrine (PE) infusion combined with positive neck pressure (NP; AF, 18 +/- 2.0 and HF, 20 +/- 0.8 mmHg) to counteract the increased carotid sinus pressure and with low levels of lower body negative pressure to counteract the increased central venous pressure. There was no group difference in the increased MAP or NP, nor was there stage difference in MAP within either group during PE infusion. However, the isolated cardiac-aortic baroreflex gains (i.e., delta HR/delta MAP) were significantly less in the HF (0.16 +/- 0.02 and 0.14 +/- 0.03 beats.min-1.mmHg-1) than in the AF (0.52 +/- 0.08 and 0.59 +/- 0.07 beats.min-1.mmHg-1) subjects at PE + NP and PE + NP + lower body negative pressure. We concluded that during steady-state increases in MAP, the sensitivity of aortic baroreflex control of HR was significantly less in the HF than in the AF subjects. PMID- 8514670 TI - Antigen-induced contraction of guinea pig isolated pulmonary arteries and lung parenchyma. AB - We characterized the kinetics of and determined the mediators involved in antigen induced contraction of pulmonary arteries (PA) and lung parenchyma isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml) induced contractions of PA rings, which reached maximum amplitude by 2 min and decayed to 50% of maximum by 4-6 min. Pyrilamine (10(-6) M) delayed the onset of contraction and decreased the peak of the response by > 50%. Metiamide (10(-4) M) partially reversed this effect. The addition of indomethacin (10(-6) M) to the combination of pyrilamine and metiamide had no significant effect. The further addition of the leukotriene (LT) D4/LTE4 receptor antagonist SKF 104353 (10(-5) M) reduced the contraction by > 80%. The maximum amplitude of antigen-induced contraction of parenchymal strips was reached by 15 min and was sustained for > 60 min. In these tissues, SKF 104353 inhibited the contraction by approximately 35%, but the histamine receptor antagonists and indomethacin had no significant effect. These results suggest that both histamine and sulfidopeptide LTs mediate antigen-induced contraction of PA, whereas sulfidopeptide LTs, but not histamine, are involved in the parenchymal response. PMID- 8514671 TI - Lung and chest wall mechanics in mechanically ventilated COPD patients. AB - By use of the technique of rapid airway occlusion, the effects of inspiratory flow, volume, and time on lung and chest wall mechanics were investigated in 10 chronic obstructive pulmonary disease (COPD) patients mechanically ventilated for acute respiratory failure. We measured the interrupter resistance (Rint), which in humans reflects airway resistance; the additional resistances due to time constant inequality and viscoelastic pressure dissipations within the lungs (delta RL) and the chest wall; and the static and dynamic elastances of lung and chest wall. We observed that 1) static elastances of lung and chest wall in COPD patients were similar to those of normal subjects; 2) Rint of the lung was markedly increased and flow dependent in COPD patients, whereas Rint of the chest wall was negligible as in normal subjects; and 3) in COPD patients, delta RL was markedly increased at all inflation flows and volumes, reflecting increased time constant inequalities within the lungs and/or altered viscoelastic behavior. The results imply increased dynamic work due to Rint and delta RL and marked time dependency of pulmonary resistance and elastance in COPD patients. PMID- 8514672 TI - Ventilation and thoracoabdominal asynchrony during halothane anesthesia in infants. AB - To evaluate the ventilatory consequences of high chest wall compliance during anesthesia in infants, we assessed the effects of halothane at different fractions of minimal alveolar concentration (0.75, 1.0, and 1.5 MAC) on ventilation and movements of the rib cage and abdomen in infants < or = 12 mo of age (group I) and children (group II) > or = 12 mo of age. Minute ventilation decreased in group I, (20.6%, 0.75 to 1.5 MAC), but the change in group II did not reach the level of statistical significance. Tidal volume decreased with halothane level between 0.75 and 1.5 MAC, and its fall was greater in group I (32.7 +/- 11.2 vs. 22.6 +/- 9.3% in group II, P < 0.05). Duty cycle, or ratio of inspiratory to total time (TI/TT), increased in group II with halothane level but did not change in group I, resulting in a decreased TI in group I at higher halothane levels. Thoracic paradox increased with halothane level in group I but not group II. The increase in thoracic paradox in association with the fall in tidal volume between 0.75 and 1.5 MAC was greater in group I than group II (P < 0.05). We conclude that smaller infants depend more on inspiratory intercostal muscle activity to stabilize the thorax, leading to a greater degree of depression of ventilation during halothane depression of inspiratory intercostal activity. PMID- 8514673 TI - Modulation of maximal inspiratory airflow by neuromuscular activity: effect of CO2. AB - To determine how maximal inspiratory airflow (VImax) is modulated by changes in airway neuromuscular activity, we analyzed pressure-flow relationships obtained during inspiration and expiration in isolated upper airways of anesthetized hyperoxic dogs at different levels of CO2. Inspiratory airflow (VI), hypopharyngeal pressure (Php), pharyngeal pressure at the flow-limiting site (FLS), and alae nasi (AN) and genioglossus (GG) electromyographic (EMG) activity were recorded while VI limitation was produced by rapidly lowering Php until VI plateaued at VImax. VImax and its mechanical determinants, pharyngeal critical pressure (Pcrit) and nasal resistance (Rn) upstream to the FLS, were measured. During hypercapnia (high CO2), VImax increased significantly during inspiration (217.3) and expiration (184.1%). These increases were associated with significant increases in phasic but not tonic AN and GG activity. They were also associated with decreases in Pcrit from -6.2 +/- 1.6 (SE) at hypocapnia to -9.3 +/- 3.0 and 11.8 +/- 3.4 cmH2O at high CO2 during expiration and inspiration, respectively. No significant changes in Rn occurred. When phasic neuromuscular activity was abolished by complete neuromuscular blockade in three dogs, these increases in VImax and decreases in Pcrit at high CO2 were eliminated. When phasic EMG activity was accentuated in four vagotomized dogs, significant increases in VImax and decreases in Pcrit were demonstrated during inspiration vs. expiration at high CO2. These findings indicate that upper airway neuromuscular activity increases VImax in the isolated upper airway by decreasing collapsibility (Pcrit) at the FLS site when neuromuscular activity is stimulated by hypercapnia. PMID- 8514674 TI - Role of endothelium-derived relaxing factor in reactive hyperemia in canine diaphragm. AB - We studied the effect of NG-nitro-L-arginine (L-NA) on reactive hyperemia in the vascularly isolated hemidiaphragm of anesthetized dogs pretreated with indomethacin. In nine animals, the diaphragm was autoperfused from the left femoral artery. Phrenic arterial flow was interrupted for 10-120 s during a control period and after 20 min of L-NA infusion (6 x 10(-4) M). Postocclusive flow and duration of hyperemia during the control period increased progressively with increasing occlusion duration. After L-NA infusion, baseline and postocclusive flow in response to all occlusions declined significantly compared with control values. However, when normalized as percentage of baseline flow, postocclusive flow remained similar to that during the control period. By comparison, the duration of reactive hyperemia was significantly shortened by L NA infusion. In five animals, we repeated the same protocol during pump perfusion of the diaphragm at a fixed flow rate. L-NA infusion increased baseline and postocclusive phrenic resistance in response to all occlusion durations; however, postocclusive phrenic resistance as percentage of baseline remained similar to control values. In addition, hyperemia durations in response to 60- and 120-s occlusions were shortened significantly by L-NA infusion. We conclude that 1) endothelium-derived relaxing factor plays an important role in the regulation of baseline vasomotor tone in the diaphragm and 2) modulation of endothelium-derived relaxing factor release contributes to the reactive vasodilatory response to transient vascular occlusion in the diaphragm. PMID- 8514675 TI - Airway smooth muscle shortening in excised canine lung lobes. AB - To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514676 TI - Intralysosomal pH and release of lysosomal enzymes in the rat liver after exhaustive exercise. AB - The mechanism underlying exhaustive exercise-induced release of lysosomal enzymes was studied in the rat liver. Exhaustive exercise resulted in the release of beta glucuronidase and cathepsin D, but not beta-glucosidase and acid phosphatase, into the blood and cytosol, suggesting that the release of lysosomal enzymes is not due to disruption of lysosomal membranes. The intralysosomal pH of the liver, which was approximately 5.5 at the resting level, rose significantly after exhaustive exercise to pH 6.3. In vitro, beta-glucuronidase and cathepsin D were released at an intralysosomal pH exceeding 6.2. In contrast, beta-glucosidase and acid phosphatase were not released. The elevation of intralysosomal pH reduced the aggregation of beta-glucuronidase and cathepsin D. The rate of ammonia accumulation increased markedly in the lysosome-enriched subcellular fraction after exercise. There was a positive relationship between the rate of ammonia accumulation and the elevation of intralysosomal pH in vitro. Lysosomes isolated after exhaustive exercise showed significantly increased osmotic fragility. Our findings suggest that, during exhaustive exercise, the accumulation of ammonia in lysosomes leads to the elevation of intralysosomal pH, resulting in the reduced aggregation of certain lysosomal enzymes. Thus, less aggregated lysosomal enzymes may be released into the cytosol through the lysosomal membrane, the permeability of which has been increased. PMID- 8514677 TI - Effect of chronic hypoxia on hypoxic ventilatory response in awake rats. AB - We compared the hypoxic ventilatory response (HVR) of two groups of unrestrained awake male rats (300-550 g): those acclimatized to hypoxia > 7 wk at simulated altitude (380 Torr, n = 12) and sea level controls (n = 8). Chronic catheters were placed in the iliac artery and vein 3-7 days before study. An "on-line" system was used to measure arterial PO2 and PCO2. Arterial blood was drawn via a roller pump past O2 and CO2 electrodes and returned to the vein. Batch samples were taken before and after HVR measurements for calibrating and determining arterial pH and hematocrit. Inspired ventilation, tidal volume, and respiratory frequency were measured with barometric pressure plethysmography at several levels of inspired O2 fraction (0.08-0.30) maintained for 15 min. For isocapnic HVR, inspired CO2 fraction was increased as necessary to maintain arterial PCO2 at the hyperoxic level. In both groups, poikilocapnic HVRs (inspired CO2 fraction = 0) were significantly less than isocapnic HVRs. Isocapnic HVRs were significantly greater in hypoxia-acclimatized (2,783 +/- 233 ml.min-1.kg-1) than in sea level control rats (1,826 +/- 106 ml.min-1.kg-1), mainly due to a significant increase in tidal volume (P < 0.05). In conclusion, relieving hypocapnia in hypoxia, by maintaining isocapnia, reveals a significant increase in the ventilatory response to arterial PO2 in awake rats with chronic hypoxia. PMID- 8514678 TI - Computer simulation of neutrophil transit through the pulmonary capillary bed. AB - One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed. PMID- 8514679 TI - Effect of soleus unweighting on stimulation of insulin-independent glucose transport activity. AB - Unweighting of the rat soleus by tail-cast suspension results in increased insulin action on stimulation of glucose transport, which can be explained, at least in part, by increased insulin binding and enhanced glucose transporter protein levels. Glucose transport is also activated by an insulin-independent mechanism stimulated by in vitro muscle contractions or hypoxia. Therefore, the purpose of this study was to determine if soleus unweighting leads to an enhanced response of the insulin-independent pathway for stimulation of glucose transport. The hindlimbs of juvenile male Wistar rats were suspended by a tail-cast system for 3 or 6 days. Glucose transport activity in isolated soleus strips (approximately 18 mg) was then assessed by using 2-deoxy-[1,2-3H]glucose (2-DG) uptake. Insulin (2 mU/ml) had a progressively enhanced effect on 2-DG uptake after 3 and 6 days of unweighting (+44 and +72% vs. control, respectively; both P < 0.001). At these same times, there was no difference between groups for activation of 2-DG uptake by maximally effective treatments with contractions (10 tetanuses), hypoxia (60 min), or caffeine (5 mM). These results indicate that the enhanced capacity for stimulation of glucose transport after soleus unweighting is restricted to the insulin pathway, with no apparent enhancement of the insulin independent pathway. PMID- 8514680 TI - Optical imaging of the ventral medullary surface of cats: hypoxia-induced differences in neural activation. AB - Large-array optical recording procedures provide the potential to examine simultaneous activity of large numbers of neurons. We applied this technique to examine regional neuronal activation on the ventral medullary surface (VMS) of cats during hypoxic challenges. VMS was exposed through a ventral surgical approach in eight adult cats under pentobarbital sodium anesthesia. Arterial pressure, end-tidal CO2, costal diaphragmatic electromyograms, and electrocardiograms were continuously monitored. A coherent image conduit with 12 microns-fiber resolution was attached to a charge-coupled device camera and positioned over the VMS. Reflected 700-nm light was digitized continuously at 2- to 3-s intervals during baseline period, hypoxic (6, 9, and 12% O2 in N2) exposure, and recovery. Forty images within each epoch were averaged and subtracted from baseline. Regional differences within the image were determined by analysis of variance procedures (alpha = 0.05). In caudal VMS, hypoxic challenges with 12% O2 consistently induced a regional diminution in reflected light (increased neural activity) that was rapid in onset and persisted for approximately 20 min after termination of exposure, well beyond the duration of discernible ventilatory alterations. In contrast, the same challenge resulted in decreased neural activity of similar duration in rostral VMS areas. Challenges with lower inspired concentrations of O2 reversed the pattern of diminished neural activity in rostral regions and led to a dose-dependent increase in neural activity, a dependency also observed in caudal VMS. We conclude that caudal VMS neurons demonstrate a unidirectional dose-dependent response pattern to hypoxic stimuli, whereas rostral VMS regions exhibit a bidirectional response to increasing hypoxic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514681 TI - Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise. AB - Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770-1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve. PMID- 8514682 TI - Indomethacin compromises hemodynamics during positive-pressure ventilation, independently of prostanoids. AB - We examined whether prostanoids contribute to the impaired cardiac function and decrease in regional blood flow induced by increasing mean airway pressure. Using microspheres, we measured cardiac output and major organ blood flow and assayed prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in blood at mean airway pressures of 5-25 cmH2O in mechanically ventilated newborn piglets treated with ibuprofen (40 mg/kg, n = 6), indomethacin (0.3 mg/kg, n = 6), or vehicle (n = 6). Blood gases and pH were stable throughout the experiments. Prostanoid levels remained constant with increasing mean airway pressure in vehicle-treated pigs and were unchanged by indomethacin. However, ibuprofen decreased the prostanoid levels at all mean airway pressures studied (P < 0.01). As ventilatory pressure was progressively increased, cardiac output decreased gradually and similarly by 42-45% (P < 0.05) in all groups. At the highest mean airway pressure, blood flow decreased to the kidneys by 37-57%, to the ileum by 58-74%, and to the colon by 53-71% (P < 0.05) in all groups. Cerebral blood flow remained constant at all ventilatory pressures regardless of the treatment. There was no difference in cardiac output and regional hemodynamics between ibuprofen- and vehicle-treated animals. However, after indomethacin, ileal blood flow at the higher ventilatory pressures was 41-46% lower and cerebral blood flow at all mean airway pressures was 14-25% lower than after the other treatments (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514683 TI - Role of postural status in the nocturnal hemodynamic patterns of nonhuman primates. AB - We compared the nocturnal hemodynamic patterns of seven tethered monkeys (Macaca mulatta) with those of seven chaired animals to determine whether the overnight changes are comparable in the two conditions. In both groups, we found a consistent hemodynamic pattern characterized by an overnight fall in cardiac output and central venous pressure and a rise in total peripheral resistance that maintained blood pressure homeostasis. The pattern of overnight change occurred despite major differences in response levels: cardiac output and central venous pressure were significantly elevated, and total peripheral resistance was significantly reduced at all times (from 1800 to 1200 h the following day) in the chaired animals relative to the tethered animals. This difference was probably due to an expanded plasma volume in the chaired animals, because stroke volume was also significantly elevated. Because the nocturnal hemodynamic pattern occurred under both conditions, it is likely that it is a stable biologic effect, which is probably related to an overnight loss in fluid volume that is not replaced in animals that sleep throughout the night. PMID- 8514684 TI - Vagal and chemoreceptor influences on abdominal muscle activity in awake lambs during hypoxia. AB - The ventilatory response to hypoxia is a complex phenomenon involving several control mechanisms. We designed this study to examine the dynamic control of abdominal muscle expiratory electromyogram (EMG) activity during room-air breathing and hypoxia and then to analyze the relative contribution of the chemoreceptors and vagal afferents. We studied 12 11- to 22-day-old awake nonsedated lambs, six intact and six vagotomized. To assess the dynamic influence of peripheral chemoreceptors on abdominal muscle expiratory activity, we performed transient testing of peripheral chemoreceptor function (pure O2 and N2 inhalation, KCN injection). To assess the influence of central chemoreceptor afferents, we compared results obtained during hypocapnic and isocapnic 15-min hypoxic runs (fractional concentration of inspired O2 0.08) in each lamb. We also compared results obtained in intact and vagotomized lambs so that the importance of vagal afferents could be assessed. We consistently observed abdominal muscle expiratory EMG activity in each lamb, whether intact or vagotomized, during baseline room air breathing; further recruitment was observed during hypoxia. We also consistently observed abdominal muscle expiratory recruitment during hypocapnic hypoxia in each lamb, although it was significantly less marked than during isocapnic hypoxia. Our transient testing of peripheral chemoreceptor function showed, furthermore, that peripheral chemoreceptor afferents dynamically modulate abdominal muscle expiratory activity. Thus, during hypoxia in 11- to 22 day-old awake nonsedated lambs, increased afferent information from peripheral chemoreceptors forcefully enhances abdominal muscle expiratory activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514685 TI - Effects of training and immobilization on VO2 and DO2 in dog gastrocnemius muscle in situ. AB - To investigate the effects of exercise training and immobilization on peak O2 uptake (VO2) and effective O2 diffusive conductance (DO2) in skeletal muscle, three groups of purpose-bred hounds [control (C), exercise trained (E), and immobilized (I)] were studied. Group E exercised on a treadmill 1 h/day, 5 days/wk for 8 wk, while groups C and I were cage confined for 8 wk, with group I undergoing left hindlimb immobilization for the last 3 wk. Thereafter, each dog's left gastrocnemius was surgically isolated, pump perfused, and electrically stimulated to elicit peak VO2 in situ at three levels of arterial oxygenation. O2 delivery [(arterial O2 concentration x muscle blood flow)/100 g muscle] was kept constant among the three groups at each level of arterial oxygenation. Compared with group C, peak VO2/100 g muscle was 38, 33, and 19% greater and DO2/100 g muscle was 71, 75, and 68% greater during normoxia, moderate hypoxia, and severe hypoxia, respectively, in group E (P < 0.02), whereas no differences from control were found in group I. We conclude that O2 delivery is not the unique determinant of peak VO2 and that exercise training improves the functional blood-tissue gas exchange properties of the muscle itself. Immobilization sufficient to reduce muscle weight by 31% and citrate synthase activity by 68% has no effect on peak VO2/100 g muscle or DO2/100 g muscle. PMID- 8514686 TI - PDC activity and acetyl group accumulation in skeletal muscle during isometric contraction. AB - The activity of pyruvate dehydrogenase complex (PDC) was studied in the human quadriceps femoris muscle during isometric contraction induced by intermittent electrical stimulation at 20 Hz. Muscle biopsy samples were obtained at rest and after 10, 20, and 46 contractions. The active form of PDC (PDCa) increased from a mean value of 26% of the total PDC at rest to mean values of 46, 78, and 80%, respectively. Muscle biopsy samples were also obtained at rest, after 46 contractions with limb blood flow intact or occluded, and after 2 min of oxidative recovery. In another experiment, muscle biopsy samples were obtained at rest, after 10 min of resting ischemia, and after 46 contractions with limb blood flow occluded. The transformation of PDC to PDCa was nearly complete, regardless of whether the blood flow was intact or occluded. However, the accumulation of acetyl groups observed during stimulation with intact blood flow was abolished when the blood flow was occluded. The absence of NADH oxidation during anoxia had no effect on the contraction-induced transformation of PDC to PDCa, but it inhibited the flux through the enzyme reaction. PMID- 8514687 TI - Muscle sympathetic nerve responses to prolonged one-legged exercise. AB - We previously demonstrated that brief dynamic one-legged knee extensions (DKE) performed in the upright position decreased muscle sympathetic nerve activity (MSNA). The present study was undertaken to investigate MSNA responses to prolonged DKE. DKE was performed for 40 min in the upright (sitting) position, and MSNA was recorded in the peroneal nerve of the contralateral leg by microneurography. DKE elicited a significant increase in mean arterial pressure (MAP) from 83 +/- 3 to 101 +/- 6 (SE) mmHg during the 5th min of exercise. The increase in MAP persisted for the remainder of exercise. In contrast, heart rate (HR) showed a gradual increase throughout the 40 min of exercise (80 +/- 3 to 110 +/- 5 beats/min at 40 min of exercise; P < 0.05). MSNA decreased from 34 +/- 3 to 28 +/- 3 bursts/min (P < 0.05) from control to the 5th min of DKE and then returned to control levels by 20 min (35 +/- 3 bursts/min) and remained unchanged for the remainder of exercise. During recovery, MSNA was significantly increased above control for 10 min postexercise (40 bursts/min) when HR and MAP had returned to control levels. These results confirm our previous finding that MSNA is decreased during the early stage of upright DKE. The two new findings are as follows: 1) prolonged DKE failed to increase MSNA above control levels, and 2) during recovery when HR and MAP are at control levels, MSNA is significantly elevated. PMID- 8514688 TI - PtiO2 and CMRO2 changes in cortex and hippocampus of aging gerbil brain. AB - Tissue O2 partial pressure (PtiO2) and O2 disappearance rates (dPO2/dt) after bilateral carotid artery occlusion were measured with recessed cathode O2 microelectrodes (tips < 3 microns) in gerbil brains (n = 38) from three age groups: young (Y, 3-6 mo), mature (M, 10-12 mo), and older (O, 18-21 mo). Mean PtiO2 values were 18.4 +/- 1.2 (SE), 14.0 +/- 0.8 (P < 0.005), and 21.2 +/- 1.0 (NS) Torr for Y, M, and O groups, respectively, in the cortex and 14.1 +/- 0.8, 15.6 +/- 0.8 (NS), and 16.1 +/- 0.8 (NS) Torr in the hippocampus (Mann-Whitney comparisons with Y). In the cortex, mean dPO2/dt declined significantly with age: -19.2 +/- 1.1, -14.2 +/- 0.9 (P < 0.001), and -12.4 +/- 0.5 (P < 0.001) Torr/s for Y, M, and O, respectively (ANOVA comparisons with Y). In the hippocampus, the respective mean dPO2/dt values were -16.4 +/- 0.8, -15.6 +/- 1.9, and -13.9 +/- 2.2 Torr/s. Although the time trend for dPO2/dt was significant (P < 0.05), mean hippocampal differences compared by ANOVA were not. In Y, mean PtiO2 and dPO2/dt were lower in the hippocampus than in the cortex (P < 0.05). Apparent Michaelis Menten constants for O2 were estimated from the O2 disappearance curves. These constants were significantly higher for the O group in the hippocampus (5.1 +/- 0.8 Torr) than in the cortex (2.7 +/- 0.6 Torr, P < 0.05). PMID- 8514689 TI - Determination of maximal power output at neuromuscular fatigue threshold. AB - The purpose of this study was to determine the maximal power output at the neuromuscular fatigue threshold (EMGFT), as estimated from electromyographic (EMG) data from representative leg muscles during cycling. The rate of rise in integrated EMG activity as a function of time (iEMG slope) was calculated at each of four constant-power-output ergometer bouts for 20 subjects. The iEMG slopes were plotted against work rates that were well described as linear functions (0.84 < R2 < 0.99). This iEMG slope vs. work rate relationship was extrapolated to zero slope to give an intercept on the power axis that was interpreted as the highest work rate sustainable without EMG evidence of neuromuscular fatigue (EMGFT). Each individual EMGFT was then expressed in terms of an O2 output (VO2) equivalent on the basis of the individual delta efficiency calculated during a linearly increasing maximal exercise test on the same bicycle ergometer. Results indicated a highly significant correlation (r = 0.92, P < 0.01) between EMGFT VO2 and anaerobic threshold VO2, as determined by conventional gas exchange criteria. The mean EMGFT VO2 (1.84 +/- 0.55 l/min) was, however, significantly greater (P < 0.01) than the anaerobic threshold VO2 (1.72 +/- 0.54 l/min). It was suggested that the EMGFT may provide an attractive alternative to the measurement of the highest work rate that can be sustained without evidence of neuromuscular fatigue. PMID- 8514690 TI - Cognitive performance and event-related brain potentials under simulated high altitudes. AB - The effects of hypobaric hypoxia on cognitive processing in humans were studied by recording event-related potentials (ERPs) from the scalp in a go/no-go reaction time (RT) paradigm under various simulated high altitudes. Most subjects indicated abrupt impairment of RT at high altitudes. RTs lengthened in association with changes in latency and amplitude of the N2-P3 components, reflecting sensory discrimination and evaluation processes. Some subjects did not suffer any changes in RT up to an extremely high altitude of 6,000 m. In the latter case, although the N2-P3 components did not undergo any changes, the P3 component was followed by a sequence of negative on-going (frontal maximum) and positive on-going (parietal maximum) slow waves. The amplitudes of these slow waves increased as altitude increased. Although these same waves appeared in the ERPs of subjects who demonstrated the increase in RTs at high altitudes, when the subjects failed in the RT task, both of the slow waves either disappeared or diminished. Such slow waves may be associated with attempts to maintain RTs against the deteriorative effects of hypobaric hypoxia. PMID- 8514691 TI - Effect of blood flow reduction on maximal O2 uptake in canine gastrocnemius muscle in situ. AB - The purpose of this study was to decrease O2 delivery to maximally working muscle by reductions in muscle blood flow (Q), while maintaining hemoglobin concentration and the arterial PO2 (PaO2) constant, to investigate how the decreases in maximal O2 uptake (VO2max) that occur with ischemia are related to changes in the estimated effective muscle O2 diffusing capacity (DO2). Additionally, the relationships among Q, DO2, O2 uptake (VO2), and effluent venous PO2 (PVO2) were used to infer whether the reductions in Q occur uniformly throughout the muscle or whether a nonuniform (greater heterogeneity of Q to VO2) pattern develops. Isolated dog gastrocnemius muscle (n = 6) was stimulated maximally at three levels of muscle blood flow (controlled by pump perfusion): control [C; 119 +/- 3 ml.100 g-1.min-1 (SE)], moderate ischemia (MI; 80 +/- 6), and severe ischemia (SI; 45 +/- 6) in random order. Arterial and venous samples were taken to measure blood gases, O2 concentration, and lactate concentration, whereas a Bohr integration technique using a model based on Fick's law of diffusion was used to estimate mean capillary PO2 and DO2 for each Q condition. VO2max fell progressively (P < 0.05) with Q, even though the O2 extraction ratio (VO2/O2 delivery) increased significantly (C = 67%, MI = 84%, SI = 90%). PVO2 and VO2max fell in proportion to each other from C to MI, but there was not a significant fall in PVO2 from MI to SI. Thus the calculated DO2 did not change between C and MI but fell in proportion to Q between MI and SI. These results suggest that with moderate Q reduction, perfusion falls relatively uniformly throughout the muscle, whereas more severe ischemia leads to nonuniform changes in Q distribution with some areas being poorly perfused to allow more adequate perfusion to other areas. PMID- 8514692 TI - Autonomic mechanisms of muscle metaboreflex control of heart rate. AB - Ischemia in active skeletal muscle induces reflex increases in systemic arterial pressure (SAP) and heart rate (HR), termed the muscle metaboreflex. When metaboreflex activation is maintained during postexercise muscle ischemia, SAP remains elevated; however, HR decreases. Why the HR responses differ with metaboreflex activation during exercise vs. during postexercise ischemia while the SAP responses are similar in each setting remains unclear. Two hypotheses were tested: 1) the increase in HR with muscle ischemia occurs predominantly via an increase in sympathetic activity, and 2) sympathetic activity to the heart remains elevated during post-exercise ischemia; however, HR decreases because of an increase in parasympathetic outflow. The muscle metaboreflex was activated in conscious dogs during treadmill exercise (3.2 kph, 0% grade) by progressively decreasing perfusion to the hindlimbs. Experiments were performed before and after muscarinic (atropine) or beta- (atenolol or propranolol) receptor blockade. In control experiments, once beyond the threshold for the reflex, the HR sensitivity of the muscle metaboreflex averaged -2.4 +/- 0.3 beats.min-1.mmHg-1 and the reflex open-loop gain averaged -3.2 +/- 0.3 (calculated as the ratio of the increase in HR or SAP to the decrease in hindlimb perfusion pressure beyond threshold). Atropine had no effect on either HR sensitivity (-2.7 +/- 0.4 beats.min-1.mmHg-1) or open-loop gain (-3.3 +/- 0.5, both P > 0.05 vs. control). However, pretreatment with beta-receptor antagonist significantly decreased both HR sensitivity (-0.7 +/- 0.1 beats.min-1.mmHg-1, P < 0.001) and open-loop gain ( 1.9 +/- 0.3, P < 0.01). During postexercise ischemia, HR decreased while SAP remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514693 TI - Exercise reduces muscle glucose transport protein (GLUT-4) mRNA in type 1 diabetic patients. AB - We examined the effect of acute exercise on muscle glucose transporter (GLUT-4) protein and mRNA concentrations in nine male type 1 diabetic patients (age 31 +/- 3 yr, body mass index 23.6 +/- 0.7 kg/m2, insulin dose 44 +/- 4 U/day, glycosylated hemoglobin 7.8 +/- 0.4%) and in nine healthy control subjects (34 +/ 1 yr, 25.3 +/- 0.8 kg/m2). Three hours of cycle ergometer exercise was performed after an overnight fast. A needle biopsy (100-150 mg) was taken from the quadriceps femoris 40 min before and immediately after the end of exercise. During exercise, plasma glucose, insulin, cortisol, and growth hormone concentrations were higher in the diabetic patients than in the control subjects. In the basal state, GLUT-4 protein and mRNA concentrations were similar in the two groups. During exercise, GLUT-4 mRNA concentration decreased by 30-45% in the diabetic patients but remained unchanged in the control subjects. GLUT-4 protein content remained unchanged in both groups. These data suggest an abnormal GLUT-4 mRNA production or degradation or both in type 1 diabetic patients during physical exercise. PMID- 8514694 TI - Cationic proteins alter smooth muscle function by an epithelium-dependent mechanism. AB - Using a perfused guinea pig tracheal tube preparation, which allows the selective application of agonists to either the serosal or luminal surface, we have investigated whether two synthetic cationic proteins, poly-L-arginine and poly-L lysine, can modify epithelium-dependent responses. With an intact epithelium, methacholine was approximately 150 times less potent when applied intraluminally than when applied extraluminally. This difference was abolished by chemically removing the epithelium with the detergent CHAPS. Intraluminal application of KCl induced a dose-related relaxation of a precontracted trachea, which was also abolished by epithelium removal. Perfusion of the luminal surface with cationic proteins for 1 h (10 micrograms/ml) increased the potency of intraluminally applied methacholine without modifying the responses to extraluminally applied methacholine. Cationic proteins also attenuated the relaxant effects of intraluminally applied KCl. These effects occurred in the absence of any overt epithelial cell damage. In contrast, when the serosal surface of the trachea was treated with poly-L-arginine, there was no modification of either methacholine induced contraction or KCl-induced relaxation. The effects of poly-L-arginine were inhibited by coperfusion with the polyanions albumin (10 micrograms/ml) or heparin (100 micrograms/ml). In contrast to cationic proteins, intraluminal perfusion with a polyanion, poly-L-aspartate (10 micrograms/ml), failed to modify either methacholine-induced contraction or KCl-induced relaxation. Our data demonstrate that cationic proteins can modify epithelium-dependent responses in the airways. Although the precise mechanisms are unclear, a role is suggested for a charge-mediated interaction with the respiratory epithelium, resulting in airway smooth muscle dysfunction. PMID- 8514695 TI - Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. AB - Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5 dibromosalicyl)fumarate (alpha alpha Hb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alpha alpha Hb, 3) human serum albumin, or 4) Ringer lactate. Mild high-output renal failure was observed in the non-cross linked Hb-treated animals but not in other groups of animals. Swine treated with Hb and alpha alpha Hb had increases in plasma creatine kinase and lactate dehydrogenase activity that were resolved within 7 days. Both Hb- and alpha alpha Hb-treated swine displayed marked elevations of mean blood pressure in the systemic (39 +/- 6 Torr) and pulmonary (20 +/- 6 Torr) circulations that continued for 3 h and were associated with reduced cardiac output and a doubling of the systemic and pulmonary vascular resistances. Oxygen delivery was equivalent, and the rate of correction of the lactic acidosis was equal in all groups. PMID- 8514696 TI - Fluid exchanges across the parietal peritoneal and pleural mesothelia. AB - In 31 anesthetized rabbits, after removal of superficial tissues, glass micropipettes filled with 0.5 M NaCl solution and connected to an electrohydraulic servo-null system were used to measure extraperitoneal interstitial fluid pressure (Pi,per) and peritoneal liquid pressure (Pliq,per) at various heights. Linear regressions relating pressure to recording height (H) were Pi,per = 1.07 - 0.27H and Pliq,per = 0.9 - 0.64H, respectively. Protein concentration (Cp;g/dl) and colloid osmotic pressure (II; cmH2O) of plasma and of peritoneal and pleural liquids were 5.48 +/- 0.38 and 24.61 +/- 3.23, 3.07 +/- 0.5 and 13.29 +/- 1.87, and 1.76 +/- 0.42 and 8.45 +/- 2, respectively. The equation relating II to Cp was II = 4.64Cp + 0.0027Cp2. Tissue fluid samples were collected with saline-soaked wicks implanted in vivo or dry wicks inserted postmortem in extraperitoneal and extrapleural interstitial spaces. After 60 and 15 min, respectively, wicks were withdrawn and centrifuged; wick fluid was analyzed in colloid osmometer for small samples. Average extraperitoneal and extrapleural II values were 14.2 +/- 2.49 and 11.94 +/- 1.52 cmH2O, corresponding to Cp of 3.07 and 2.57 g/dl, respectively. The average net pressure gradient, assuming reflection coefficient and hydraulic conductivity (Negrini et al. J. Appl. Physiol. 69: 625-630, 1990; 71: 2543-2547, 1991), was 1.18 and 0.98 cmH2O for parietal peritoneal and pleural mesothelia, respectively, favoring filtration from the extraserosal interstitia into the serosal cavities. Total parietal peritoneal filtration was 1.49 ml.kg-1.h-1, approximately 15-fold higher than that for pleural mesothelium. PMID- 8514697 TI - Physical training attenuates phosphocreatine and long-chain acyl-CoA alterations in diabetic rat heart. AB - This study was designed to assess the effect of physical training on high-energy phosphate levels in the heart of diabetic rats. Diabetes was induced with streptozocin (50 mg/kg), and exercise training was carried out on a treadmill with a progressive 10-wk program. Plasma glucose levels at the end of the training program showed only a small improvement of the diabetic state in trained animals (21.7 +/- 1.3 vs. 24.4 +/- 0.8 mmol/l; P < 0.05). The lower heart rate observed in sedentary diabetic rats (279 +/- 6 vs. 356 +/- 5 beats/min; P < 0.001) was improved by physical training (301 +/- 8 beats/min; P < 0.05 vs. sedentary diabetics). Significantly lower phosphocreatine levels were found in sedentary diabetic rats (12.0 +/- 0.7 mumol/g dry wt) than in sedentary control rats (15.0 +/- 0.9 mumol/g dry wt; P < 0.05) but not in trained diabetic rats (13.7 +/- 0.7 mumol/g dry wt). ATP levels were not affected by diabetes but were increased by training. The increased long-chain acyl-CoA levels in sedentary diabetic rats (146 +/- 7 vs. 119 +/- 8 mumol/g dry wt in sedentary control rats; P < 0.05) were improved by training (138 +/- 6 mumol/g dry wt; P > 0.05 vs. sedentary control rats). These data indicate that the diminution in phosphocreatine levels observed in the heart tissue of chronically diabetic rats can be attenuated by an exercise training program. PMID- 8514698 TI - ARDS-like lung injury produced by endotoxin in platelet-activating factor-primed rats. AB - We recently reported that the combined administration of lipopolysaccharide (LPS) and platelet-activating factor (PAF) in rats, at doses that are completely devoid of any effect when given alone, caused lung injury characterized by neutrophil adhesion to lung capillaries and postcapillary venules, neutrophil accumulation in the lung parenchyma, platelet-fibrin deposits in postcapillary venules, and pulmonary edema. A marked increase in lung myeloperoxidase activity and an elevation of serum tumor necrosis factor-alpha and thromboxane B2, along with leukopenia and thrombocytopenia, were also noticed. The present study aimed to examine whether repeated LPS-PAF stimulus can cause progressive lung injury reminiscent of adult respiratory distress syndrome (ARDS). A second LPS-PAF challenge, 4 h (n = 11) after the original challenge, induced mortality (69% at 24 h, P < 0.01) and some of the pathological changes seen in clinical ARDS, including severe pulmonary edema, alveolar proteinaceous exudates, monocytic infiltration, and a further increase in lung myeloperoxidase activity (700%, P < 0.01). Repeated LPS-PAF dosing also resulted in sustained increased serum tumor necrosis factor-alpha levels (1,610 +/- 470 pg/ml, P < 0.01) and further exacerbation of the leukopenia (-68 +/- 6%, P < 0.01) and thrombocytopenia (-65 +/- 8%, P < 0.01). These data suggest that repeated LPS-PAF actions are sufficient to elicit pathophysiology of ARDS-like lung injury. PMID- 8514699 TI - Influence of NREM sleep on respiratory-related cortical evoked potentials in normal humans. AB - Sleep substantially alters respiratory system responses to a variety of ventilatory stimuli. This could, to some extent, be a product of a sleep-induced decrement in respiratory afferent traffic to the cortex or cortical influences on central respiratory neurons. To investigate this, we determined the effect of non rapid-eye-movement (NREM) sleep on cortical evoked potentials produced by rapid onset inspiratory negative-pressure generations in the airway of seven normal subjects. Mean electroencephalographic activity at Cz-C3 and Cz-C4 for each subject was obtained by signal averaging. For Cz-C3, four respiratory-related cortical evoked potentials (P1, N1, P2, N2) occurred during wakefulness with latencies of 72 +/- 8, 128 +/- 9, 231 +/- 12, and 340 +/- 15 ms and amplitudes of 2.7 +/- 1.1, -3.2 +/- 1.1, 3.0 +/- 0.9, and -2.1 +/- 1.0 microV, respectively. During sleep, amplitudes of N1 and P2 were much greater (-9.4 +/- 1.3 and 14.1 +/ 1.7 microV, respectively; P < 0.05) and the latencies of P1, N1, and P2 (116 +/- 16, 244 +/- 24, and 664 +/- 75 ms, respectively) were substantially prolonged (P < 0.05). We conclude that respiratory-related cortical evoked potentials produced by negative-pressure generations in the airway during wakefulness are profoundly altered by NREM sleep. Their latencies are prolonged, magnitudes are increased, and the waveform is altered to resemble a K-complex. This altered sensory processing may impair respiratory responses during NREM sleep. PMID- 8514700 TI - Variability over time of complement activation induced by air bubbles in human and rabbit sera. AB - Complement activation induced by air bubbles in rabbit and human sera was studied by measuring the generation of anaphylatoxin des-Arg-C5a. des-Arg-C5a was quantified by sandwich enzyme-linked immunosorbent assays based on neoepitope specific anti-des-Arg-C5a monoclonal antibodies. Air bubbles were continuously introduced to serum via a calibrated microflowmeter, and the serum was incubated at 37 degrees C for 30 min. Air bubbles clearly generated increased amounts of des-Arg-C5a compared with corresponding levels in control serum, and a dose dependent effect was also noted. Strong positive correlations between des-Arg-C5a concentrations in control sera and sera incubated with air bubbles at a flow of 0.5 ml/min were found. To study variation over time, serum was obtained at regular intervals from six rabbits and from six healthy humans during 66- and 196 day periods, respectively. A pronounced intraindividual variability over time was thus observed. The reason for the large variability is at present unknown. We conclude that the sensitivity of complement to activation by air bubbles is not an inherent, static feature of the complement system of an individual. Therefore single-point analysis of complement activation by air bubbles appears to be an inappropriate parameter by which to differentiate a "sensitive" or "insensitive" complement system between individuals. PMID- 8514701 TI - Recovery of respiratory sinus arrhythmia in detoxified alcoholic subjects. AB - Although most alcoholic subjects show little autonomic dysfunction, severe alcoholic subjects may have pathological changes in autonomic nerves. We asked if respiratory sinus arrhythmia amplitude (RSA), an index of vagal cardiac control, is decreased in alcoholism and, if so, whether the decrease is reversed with abstinence. RSA was assessed in 17 normotensive alcoholic subjects (A) at 1, 4, 12, and 24 wk of abstinence after detoxification and at similar intervals in 17 controls (C) matched for age, race, and gender. Subjects were studied in both supine and seated positions while breathing in a prescribed deep (> 50% vital capacity) and slow (5-7/min) pattern. Mean heart rate (HR) was determined over 30 s from the electrocardiogram; RSA (the difference between maximum and minimum instantaneous HRs after inspiratory onset) was determined from 10 consecutive breaths. In C, both HR (supine: 61.5 +/- 2.2 beats/min; seated: 71.3 +/- 1.7 beats/min; P < 0.002) and RSA (supine: 22.5 +/- 1.0 beats/min; seated: 28.4 +/- 1.4 beats/min; P < 0.003) were higher when seated than when supine, but neither HR nor RSA varied over 24 wk. At week 1 of abstinence, HRs for A were higher than those for C (supine: 74.2 +/- 2.3 beats/min, P < 0.001; seated: 83.2 +/- 2.7 beats/min, P < 0.003), but by week 24, both seated and supine values returned to control levels. RSA in A at week 1, was only one-half that of C (supine: 11.1 +/- 1.4 beats/min, P < 0.001; seated: 14.7 +/- 1.9 beats/min, P < 0.001) and independent of body position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514702 TI - Effects of eccentric and concentric exercise on muscle glycogen replenishment. AB - Eccentric contractions appear to reduce muscle glycogen replenishment during the 1- to 10-day period after exercise. The main purpose of this study was to determine whether consuming a large amount of carbohydrate (1.6 g.kg-1.h-1) during the 4 h after glycogen-reducing exercise would produce different patterns of glycogen replenishment in human muscle that had undergone either eccentric or concentric contractions approximately 2 or 48 h earlier. Subjects cycled for 75 min and undertook interval exercise to deplete glycogen on days 1 and 3. After cycling exercise on day 1 only, subjects performed 10 sets of 10 repetitions of either concentric or eccentric contractions in opposite legs. During the 4 h after exercise, subjects consumed 0.4 g carbohydrate/kg body wt every 15 min. Biopsies were obtained immediately before the feedings and 4 h later, and blood was sampled every 15 min. For days 1 and 3 combined, total integrated areas for the glucose and insulin response curves averaged 1,683 mumol.ml-1.240 min-1 and 21,450 microU.ml-1.240 min-1, respectively. For days 1 and 3 combined, muscle glycogen replenishment after concentric exercise averaged 10 mmol.kg-1.h-1. On day 1 glycogen replenishment was similar for subjects performing either concentric or eccentric contractions. On day 3, however, glycogen replenishment was 25% lower (P < 0.05) in muscle that had undertaken eccentric contractions 48 h earlier than in concentrically exercised muscle. In conclusion, glycogen replenishment can be stimulated to a high rate when a large amount of carbohydrate is consumed after glycogen-depleting concentric exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514703 TI - Distribution of blood flow in the perfused tracheae of sheep: a search for arteriovenous anastomoses. AB - The possible existence of arteriovenous anastomoses (AVAs) in the tracheobronchial circulation has been largely ignored; however, their presence would have many implications. Here we have searched for AVAs in the tracheal circulation of seven anesthetized sheep that were ventilated through a low cervical tracheostomy. Arteries to the midcervical trachea were isolated and perfused in situ at systemic blood pressure; blood flow was measured with an electromagnetic flow probe. A vein draining the perfused segment was cannulated. Radiolabeled microspheres (16 microns diam) injected into the arterial inflow of the perfusion indicated the distribution of blood flow (cervical trachea, 69.9 +/ 4.55% (SE); esophagus, 15.1 +/- 3.9%; connective tissue and blood vessels near trachea, 9.5 +/- 1.8%; lymph nodes, 4.0 +/- 2.2%; skeletal muscle, 0.17 +/- 0.07%; trachea below intubation, 0.00%; larynx, 0.00%; other tissues 0.81 +/- 0.32%). Less than 0.6% of the activity was detected in the tracheal venous blood and lungs, indicating little shunting via AVAs. Within the trachea, blood flow (per wet weight of tissue) to the mucosa overlying smooth muscle was approximately 25% of that to the mucosa overlying cartilage. Intra-arterial infusion of methacholine doubled perfusion blood flow without altering the proportion of shunted blood. Within the trachea, blood flow increased most to the mucosa overlying smooth muscle and to smooth muscle. In conclusion the contribution of AVAs to total blood flow in the cervical trachea is < 1%. PMID- 8514704 TI - Effect of entrainment time on pulmonary deposition of cigarette smoke in dogs. AB - Chronic inhalation of tobacco smoke can produce a nonuniform pattern of lung disease, with apical (nondependent) areas affected more often and more severely than other lung regions. This localized tissue damage might be the result of uneven deposition of inhaled smoke aerosol. There is some evidence to suggest that the way in which an aerosol is inhaled can influence its deposition in the lung. This study sought to determine the effects of entrainment timing on the deposition of tobacco smoke in the lung. Anesthetized mechanically ventilated dogs (n = 14) inhaled 35-ml boluses of 14C-labeled mainstream cigarette smoke once per minute in either a supine or erect posture. Boluses were entrained at the start of inspiration (group 1) or at midinspiration (group 2). Lungs were removed, sectioned, and assayed for 14C. Group 1 lungs experienced deposition in regions distant from the tracheal axis, with peripheral lung units averaging twice the deposition of 14C as central units. Group 2 lungs had a more uniform 14C distribution pattern. Early smoke entrainment favored peripheral deposition. One explanation for this finding is that peripheral lung units may have shorter time constants, thus filling sooner and more completely than those located centrally. PMID- 8514705 TI - A programmable inspiratory flow generator for aerosol bolus delivery. AB - A microcomputer-controlled system that generates a discrete digital approximation of a desired inspiratory flow profile is described. Discrete flows between 0 and 387.5 ml/s can be achieved in increments of 12.5 ml/s with five solenoid valves. This pneumatic digital-to-analog converter is coupled to a mixing apparatus so that boluses of aerosol can be delivered at precise moments during an inspired breath. Between bolus deliveries, the system provides maintenance ventilation and allows flow pattern, tidal volume, inspiratory-to-expiratory time ratio, and respiratory rate to be programmed as desired. PMID- 8514706 TI - Effects of chronic hypoxia and exercise on plasma erythropoietin in high-altitude residents. AB - The present study was performed to evaluate the effects of chronic inspiratory hypoxia and its combination with physical exercise on plasma erythropoietin concentration ([EPO]). Eight natives from the Bolivian Plateau were investigated at 3,600 m above sea level at rest as well as during and up to 48 h after exhaustive exercise (EE) and 60 min of submaximal (60%) cycle ergometer exercise (SE). Ten sea-level subjects were used as a control group for resting values. The mean resting plasma [EPO] of the high-altitude group (19.5 +/- 0.7 mU/ml) did not differ from that of the sea-level group (18.1 +/- 0.4 mU/ml) but was higher than would be expected from the relationship between [EPO] and hematocrit at sea level. Five hours after both types of exercise, [EPO] decreased by 2.1 +/- 0.8 (EE, P < 0.01) and 1.6 +/- 0.8 mU/ml (SE, P < 0.05); 48 h after SE, [EPO] increased by 2.6 +/- 0.9 mU/ml (P < 0.05). It is concluded that 1) high-altitude natives need relatively high [EPO] to maintain their high hematocrit and 2) exercise at low basal arterial PO2 does not directly increase plasma [EPO] in high-altitude residents but seems to exert suppressive effects. PMID- 8514707 TI - Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle. AB - In the chronic stretch model, muscle fiber hyperplasia precedes fiber hypertrophy [Alway et al. Am. J. Physiol. 259 (Cell Physiol. 28): C92-C102, 1990]. This study was undertaken to determine if an intermittent stretch protocol would induce fiber hypertrophy without fiber hyperplasia. A weight equalt to 10% of the bird's mass was attached to the right wing of seven adult quail while the left wing served as the intra-animal control. The weight was attached to the wing for 24-h periods interspersed with a 48- to 72-hr rest interval. The actual stretch time was 5 days while the length of the treatment period was 15 days. Muscle mass and length increased significantly 53.1 +/- 9.0 and 26.1 +/- 7.3% in the stretched anterior latissimus dorsi. Fiber number, which was determined from a histological section in the midregion of the muscle, did not change (control 1,651.6 +/- 94.8; stretch 1,626.0 +/- 70.9). The slow tonic fiber areas increased significantly an average of 28.6 +/- 5.7%, whereas the fast fibers increased 18.5 +/- 8.4% when compared with control values. Mean fiber area (average of slow and fast fibers) increased significantly by 27.8 +/- 6.0% in the stretched anterior latissimus dorsi. There were no differences in the percentage of slow fibers or volume density of noncontractile tissue. These data indicate that muscle adapts differently to intermittent stretch than it does to chronic stretch despite an equivalent load and stretch duration. In contrast to chronic stretch, 5 days of intermittent stretch produces muscle fiber hypertrophy without fiber hyperplasia. PMID- 8514708 TI - Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting. AB - Antioxidants such as glutathione may play a role in prevention and treatment of several lung diseases. Liposomes can be used to deliver antioxidants to the lung and increase their retention. In addition, liposomes alone may protect against oxidant-induced damage. In addition, liposomes alone may protect against oxidant induced damage. This study was designed to characterize the retention and distribution of liposomes in the lung under normal circumstances and during either fasting, exposure to 100% oxygen, or a combination of the two. Positively charged liposomes, consisting of phosphatidylcholine (PC), cholesterol, and stearylamine plus either [14C]cholesterol or [3H]PC, were instilled intratracheally. Five minutes to 5 days later the lungs were removed and the radioactivity determined. Both [14C]cholesterol and [3H]PC labels had prolonged and equal retention in the lung, but their distribution within lung compartments differed. The cholesterol label increased in lung tissue over time, comprising 78% of the remaining label after 5 days, whereas the PC label persisted at high levels in lavage fluid and became equally distributed between lung tissue and bronchoalveolar lavage fluid. Fasting had little effect on the retention of the labels and no effect on their distribution within the lung. Exposure to 100% oxygen increased lung retention of both radiolabels and altered their distribution such that [14C]cholesterol label decreased and [3H]PC label increased in lung tissue. These results demonstrate the prolonged retention of intratracheally administered liposomes or their components in the lung and the effects of two clinically relevant conditions, fasting and hyperoxic exposure. Furthermore, they provide a basis for designing future studies using liposomes. PMID- 8514709 TI - Pulmonary and systemic vascular responsiveness to TNF-alpha in conscious rats. AB - Endotoxin decreases pulmonary vascular reactivity. Because tumor necrosis factor alpha (TNF-alpha) is a primary mediator of endotoxemia, we tested whether TNF alpha altered pulmonary vascular reactivity in conscious adult female rats. Osmotic pumps were implanted intraperitoneally, and low-dose TNF-alpha (62 micrograms, TNF62; n = 7), high-dose TNF-alpha (> or = 250 micrograms, TNF250; n = 5), or saline (n = 5) was administered for 2 wk. Pulmonary pressor responses to 14% O2 and angiotensin II (ANG II, 0.0206 micrograms/min for 10 min) were measured without (day 13) or after (day 14) administration of nitro-L-arginine (4.4 mg/kg iv), an inhibitor of endothelium-derived relaxing factor (EDRF). TNF alpha administration slightly decreased (P < or = 0.08) baseline pulmonary arterial pressure in TNF250 rats and decreased (P < or = 0.05) hypoxia- and ANG II-induced constrictions in TNF62 and TNF250 rats. Whereas nitro-L-arginine potentiated (P < or = 0.05) pressure responses in control rats, it had no effect on hypoxic responses in TNF-alpha-treated rats. Nitro-L-arginine increased (P < or = 0.05) ANG II-induced vasoconstriction in TNF-alpha-treated rats, but the pulmonary arterial pressure response was still lower (P < or = 0.05) in TNF250 than in control and TNF62 rats. These results suggest that chronic TNF-alpha decreases 1) pulmonary vascular reactivity in the intact rat, 2) hypoxic pulmonary vasoconstriction by a mechanism that is independent of EDRF, and 3) ANG II-induced constriction by a mechanism that is partly EDRF dependent. PMID- 8514710 TI - Cervical sympathectomy reduces the heterogeneity of oxygen saturation in small cerebrocortical veins. AB - This study evaluated the hypothesis that the peripheral sympathetic nervous system is one of the factors increasing the heterogeneity of venous O2 saturation in selective brain regions. Regional cerebral blood flow and O2 saturation were determined in the anterior cortex, posterior cortex, and medulla of either sham operated or bilaterally sympathectomized Long-Evans rats. Cerebral venous O2 saturations, indicating the balance between local O2 supply and consumption, were found to be significantly more heterogeneous in the sham-operated group. In the anterior cortex, the coefficient of variation [100(SD/mean)] for the sham operated animals was 22.4%. Sympathectomy significantly reduced this heterogeneity in the anterior cortex through a reduction in the number of low O2 saturation veins (coefficient of variation 11.7%). Blood flow and O2 consumption in the anterior cortex were not different between groups. The effects of sympathectomy in the posterior cortex were similar to those in the anterior cortex. However, sympathectomy did not alter any measured variables in the medulla. Thus, bilateral superior cervical ganglionectomy reduced the heterogeneity of cerebrocortical venous O2 saturation by reducing the number of low O2 saturation veins in the rostral part of the brain. PMID- 8514711 TI - Ventilatory response to oxygen after eucapnic hypoxia in conscious dogs. AB - In humans the ventilatory [minute ventilation (VI)] response to sustained hypoxia is biphasic: an initial brisk increase followed by a decline is usually seen. However, in adult dogs, the ventilatory response to a similar stimulus shows no decline. To evaluate if central ventilatory drive is altered by sustained hypoxia, we measured the lowest ventilation (nadir) as the lowest moving average of seven sequential breaths within 200 s after transition to hyperoxia (100% O2) after 3 different exposures: room air, 4-min (brief) eucapnic hypoxia (arterial O2 saturation = approximately 80%), and 12-min (prolonged) eucapnic hypoxia. The nadir hyperoxic VI after brief hypoxia (2.7 +/- 0.2 l/min) was similar to that after room air (2.6 +/- 0.2 l/min; P > 0.05), with both less than prior room air mean VI (P < 0.05). The nadir after prolonged hypoxia (3.5 +/- 0.3 l/min) was significantly greater than that after brief hypoxia (P < 0.05). This suggests that central ventilatory drive increases in conscious dogs after sustained eucapnic hypoxia. The reason for the difference in central ventilatory response to hypoxia between conscious dogs and adult humans is unexplained. PMID- 8514712 TI - Influence of carbohydrate loading on fuel substrate turnover and oxidation during prolonged exercise. AB - This study compared liver glucose turnover, blood glucose oxidation, and muscle glycogen utilization in 15 male endurance-trained cyclists who rode for 180 min at 70% of maximal O2 consumption in either a carbohydrate-(CHO) loaded (CL) or a non-CHO-loaded (NL) state. Total CHO oxidation during exercise was similar in the CL and NL subjects (492 +/- 77 vs. 448 +/- 43 g, respectively), as were blood glucose oxidation (103 +/- 19 vs. 99 +/- 7 g, respectively) and liver glucose appearance (110 +/- 15 vs. 127 +/- 16 g, respectively). However, total muscle glycogen utilization was greater in CL than NL subjects (134 +/- 11 vs. 95 +/- 12 mmol/kg wet wt; P < 0.05), the former of which had higher muscle glycogen content at the start (194 +/- 4 vs. 124 +/- 7 mmol/kg wet wt; P < 0.05) and throughout the trial. Whereas high rates of muscle glycogen breakdown were maintained throughout the trial in CL subjects, rates of muscle glycogenolysis in NL subjects decreased to 26 mmol.kg wet wt-1.h-1 after 60 min of exercise (P < 0.05) when their muscle glycogen content had declined to 70 mmol/kg wet wt. Comparable rates of blood glucose and overall CHO oxidation in CL and NL subjects, despite a slowing of muscle glycogenolysis in the NL group, could be explained by an accelerated breakdown of glycogen in the nonworking muscles to redistribute CHO (lactate) to the working muscles for oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514713 TI - Blood flow distribution to upper airway muscles. AB - Radiolabeled (15-microns) microspheres were used to measure blood flow to upper airway muscles [alae nasi (AN), intrinsic laryngeal, tongue, cervical strap, and hyoid musculature], diaphragm (DI), and parasternals (PS) during spontaneous breathing in 24 anesthetized tracheotomized supine dogs. Six dogs were also studied while -28 +/- 3 (SE) cmH2O tracheal airway pressure was generated against an inspiratory resistance (IR) (upper airway bypassed). Blood flow to posterior cricoarytenoid muscle (PCA) [24.0 +/- 2.1 (SE) ml.min-1.100 g-1] was greater than that to DI (18.0 +/- 2.3 ml.min-1.100 g-1) and comparable to that to PS (21.4 +/- 2.9 ml.min-1.100 g-1). Blood flow per unit weight did not differ between AN, tongue muscles, laryngeal adductors, cervical strap muscles, and cricothyroid (CT). Average blood flow to these muscles was only 8.0 +/- 0.8 ml.min-1.100 g-1. With the exception of CT, blood flow to these upper airway muscles was less than that to DI and PCA. Relative to blood flow during spontaneous breathing, IR loading increased blood flow to AN by a factor of 7.5, to PCA by 3.4, to DI by 3.2 and to PS by 1.9. There was no change in blood flow in the other muscles during loading. Our results show that at rest blood flow to main glottic dilator (PCA) is similar to that to main inspiratory muscles. Furthermore, in response to an IR load, blood flow to PCA and AN increased by an equivalent or greater amount than that to DI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514714 TI - Cerebellar control of expiratory activities of medullary neurons and spinal nerves. AB - Expiratory-related activities of spinal nerves are augmented after stimulation of the infracerebellar nucleus of the cerebellum. These stimulations alter neither inspiratory spinal neural activities nor inspiratory and expiratory laryngeal neural activities. It was hypothesized that efferents from the infracerebellar nucleus impinge on spinal motoneurons by a pathway that bypasses the medulla. In decerebrate, paralyzed, and vagotomized cats, phrenic and expiratory triangularis sterni activities and activities of medullary respiratory neurons were recorded. During infracerebellar stimulation, activities increased for expiratory bulbospinal neurons and neurons with tonic discharge patterns. After unilateral ablation of the infracerebellar nucleus by kainic acid, triangularis sterni discharge was eliminated and activities of expiratory bulbospinal neurons continued at reduced frequencies. Stimulations of the anterior interposed nucleus caused both inspiratory and expiratory activities to increase, whereas no systematic changes followed stimulations of the vermis. Results establish that at least a portion of the changes in expiratory activities of spinal motoneurons after perturbations of the infracerebellar nucleus occurs secondarily to changes in activities of medullary neurons. The possibility of separate cerebellar projections to medullary and spinal neurons is discussed. PMID- 8514715 TI - Influence of simulated microgravity on the VO2 max of nontrained and trained rats. AB - Head-down suspension (HDS) of rats has evolved as a useful model for the simulation of a microgravity environment. Previous HDS experiments with rats have shown an impaired capacity to perform aerobic exercise as demonstrated by reductions in maximum oxygen consumption (VO2 max), treadmill run time (RT), and mechanical efficiency (ME) of treadmill running at submaximal conditions. To determine whether endurance training (TR) before HDS would modify exercise performance, male Sprague-Dawley rats were assigned to nontrained (NT) or TR groups for 6 wk and exposed to HDS or cage control (CC) conditions for 29 days. The rats were tested for VO2 max, RT, and ME before treatment and on days 7, 14, 21, and 28. In addition, water and electrolyte excretion was measured on days 1 and 21 of the experimental period. Before HDS, the TR rats had significantly higher measures of VO2 max (15%) and RT (22%) than the NT rats. On day 28, HDS was associated with significant reductions in absolute VO2 max (ml/min) in TR ( 30%) and NT (-14%) rats. Relative VO2 max (ml.min-1.kg-1) was significantly reduced in TR (-15%) but not NT rats. Similar reductions in RT occurred in TR ( 37%) and NT (-35%) rats by day 28. ME was reduced 22% in both TR and NT rats after 28 days of suspension. HDS elicited diuresis, natriuresis, and kaliuresis in TR rats after 21 days but not after 24 h. In contrast, HDS-NT rats exhibited no diuretic, natriuretic, or kaliuretic responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514716 TI - Effect of IgG1 and its fragments on resting membrane potential of isolated tracheal myocytes. AB - We enzymatically isolated airway smooth muscle cells from the trachea of guinea pigs (400-600 g body wt). After removal of connective tissue, strips of trachealis muscle were cleaned under a dissecting microscope and incubated with collagenase (type I, 1 mg/ml) and elastase (type I, 15 U/ml) for 20 min. Cells were resuspended in Dulbecco's modified Eagle's medium and seeded on 1.5% gelatin coated Petri dishes (35 mm). The viability of cells was assessed by trypan blue exclusion. Individual myocytes were impaled with glass microelectrodes (input resistance 90-100 M omega). Resting membrane potential (Em) was determined before and after administration of 1) immune serum, 2) highly purified specific immunoglobulin G1 (IgG1), and 3) enzymatically prepared fragments of IgG1-F(ab')2 and Fc. We found that 1) Em of isolated tracheal myocytes is -60.5 +/- 0.5 mV; 2) some myocytes exhibit spontaneous electrical rhythm with mean frequency of 16.9 +/- 12 min-1 and mean amplitude of 3.7 +/- 0.6 mV; 3) immune serum, IgG1, and Fc fragments induced a biphasic change in Em: the initial mean depolarization (-51.5 +/- 0.8 mV) was followed by a steady-state hyperpolarization (-68.3 +/- 0.6 mV); and 4) pretreatment of myocytes with amiloride (10(-5) M) or exposure of myocytes to a low-sodium environment prevented changes in Em induced by the passive in vitro sensitization. It is likely that airway smooth muscle cells have a low affinity Fc receptor, the occupancy of which leads to activation of amiloride sensitive sodium influx. PMID- 8514717 TI - Phrenic and sympathetic nerve responses to glutamergic blockade during normoxia and hypoxia. AB - Because hypoxia increases brain extracellular glutamate levels, we hypothesized that gasping and increased sympathetic activity during severe hypoxia result from glutamergic excitation. To test this hypothesis, we exposed anesthetized paralyzed vagotomized glomectomized cats to hypoxia before and after N-methyl-D aspartate (NMDA) glutamergic blockade (MK-801, 1 mg/kg iv) or non-NMDA blockade (NBQX, 3 mg/kg iv) while monitoring phrenic neurogram (PN) and inspiratory synchronous (ISSN) and tonic (TSN) activity in cervical sympathetic neurogram (SN). Before hypoxia, MK-801 caused apneusis and reduced PN and ISSN amplitude by 38 and 84%, respectively, but TSN activity was unaffected. During hypoxia, MK-801 had no effect on PN gasping or TSN activity but reduced ISSN amplitude during gasping. Before hypoxia, NBQX reduced PN and ISSN amplitude by 54 and 60%, respectively but did not affect inspiratory timing or TSN activity. Gasping activity in PN and ISSN and TSN activity during hypoxia were unaffected by NBQX. We conclude that 1) ionotropic glutamergic receptor activation is important for eupneic phrenic patterning but is not involved in genesis of gasping, 2) NMDA receptor activation is involved in integration of respiratory and sympathetic activity, and 3) changes in TSN activity are independent of ionotropic glutamergic receptor activation. PMID- 8514718 TI - Vagal control of guinea pig tracheal smooth muscle: lack of involvement of VIP or nitric oxide. AB - Contractions of the vagally innervated guinea pig tracheal tube preparation were induced by 1) stimulation of the preganglionic cervical vagus nerve (PGS), 2) activation of postganglionic intrinsic nerves by use of transmural stimulation (TMS) in the presence of hexamethonium, and 3) exogenous application of spasmogens, acetylcholine (ACh) and histamine. Contractions were recorded as increases in intraluminal pressure of the sealed Krebs-filled tube preparation. In the absence of basal tone, contractions induced by both PGS and TMS were monophasic. When the tone was raised with histamine (1 microM), the rapid contractions were followed by a slow relaxation during TMS but not during PGS. There was no evidence for any involvement of the putative inhibitory nonadrenergic noncholinergic neurotransmitters vasoactive intestinal peptide (VIP) and nitric oxide (NO) in the response to PGS, because neither the peptidase alpha-chymotrypsin nor the NO synthase inhibitor NG-nitro-L-arginine affected PGS induced contractions. However, both alpha-chymotrypsin and NG-nitro-L-arginine facilitated contractions induced by TMS, suggesting that both VIP and NO are involved in responses to TMS. The facilitation of TMS-induced contractions by NG nitro-L-arginine was unaffected by epithelium removal. Therefore, neither VIP nor NO appears to be released during PGS, but both are released during TMS, and the generation of NO during TMS is independent of the epithelium. PMID- 8514719 TI - Capillary filtration coefficients using laser densitometry and gravimetry in isolated dog lungs. AB - We compared pulmonary capillary filtration coefficients (Kf,c) using measurements of transcapillary filtration rates based on laser densitometry of perfusate hematocrit changes (Jy,l) and gravimetric measurement of the rate of lobe weight gain (delta Wt/delta t) after an increase in capillary pressure (Pc) in isolated autologous blood-perfused dog lungs. Although the lobe weight increased at a rate that decreased with time, the densitometric filtration rate was relatively constant over time. Kf,c values were calculated in milliliters per minute per centimeter water per 100 g from filtration rates obtained by 1) extrapolation of the delta Wt/delta t from 3 to 10 min back to time 0 [Kf,c(0)], 2) use of the slope of the line fitted to the delta Wt/delta t and Jv,l values obtained after three stepwise increases in Pc [Kf,c(slope)], and 3) use of delta Wt/delta t and Jv,l values obtained 10, 20, and 30 min after either a constant 30-min or three 10-min stepwise increases in Pc [Kf,c(t)]. The mean Kf,c(0) values ranged from 0.171 +/- 0.024 to 0.188 +/- 0.070 and were not significantly different between vascular pressure states. These Kf,c(0) values were significantly higher than all gravimetric or densitometric Kf,c(t) or Kf,c(slope) values that ranged from 0.037 to 0.100. Kf,c(t) values were not statistically different from each other by use of either method, but the gravimetric Kf,c(slope) was significantly higher than the densitometric value. Therefore, extrapolated Kf,c(0) probably overestimates endothelial barrier Kf,c because of persistent vascular stress relaxation after a vascular pressure increase. Adjustment of tissue Starling forces may occur rapidly after an increase in filtration pressure. PMID- 8514720 TI - Tissue-specific noradrenergic activity during acute heat stress in rats. AB - The purpose of this study was to determine whether nonexertional heat stress alters the behavior of internal organ and skeletal muscle sympathetic nervous system (SNS) activity in unrestrained conscious rats. Norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of decline in tissue NE concentration after synthesis blockade was used to estimate SNS activity in the left ventricle, kidney, liver, adrenal gland, and soleus and extensor digitorum longus muscles of the hindlimb. Male Sprague-Dawley rats (250 320 g) were maintained in thermoneutral control conditions (ambient temperature = 24 degrees C, n = 10) or exposed to an ambient temperature of 42 degrees C until a colonic temperature (Tc) of 39.5 or 41.0 degrees C (n = 10 each) was attained. During heating, as Tc rose from control levels (approximately 38 degrees C) to 41.0 degrees C, mean arterial pressure and heart rate increased from 120 +/- 3 to 141 +/- 3 mmHg and from 381 +/- 4 to 420 +/- 5 beats/min, respectively (P < 0.05). There was a strong trend for increased NE turnover rates in the left ventricle, liver, and adrenal gland in NE synthesis-blocked rats attaining a Tc of 39.5 degrees C compared with the normothermic values, whereas the turnover rate in the kidney was significantly elevated at this level of hyperthermia (126%) vs. the control condition. In animals heated to a Tc of 41.0 degrees C, the NE turnover rate was markedly increased in the left ventricle (590%), kidney (531%), liver (262%), and adrenal gland (602%) compared with normothermic control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514721 TI - Acid aspiration-induced acute lung injury causes leukocyte-dependent systemic organ injury. AB - The adult respiratory distress syndrome is a form of acute lung injury (ALI) that is frequently associated with systemic organ injury and often occurs in the setting of wide-spread inflammatory cell activation. However, whether conditions that lead to ALI result in systemic organ injury is unclear. This study was designed to test the hypothesis that ALI induced by acid aspiration will not result in systemic organ injury. Morphological alterations and lymph-to-plasma protein ratios were measured in autoperfused cat ileum preparations of four control animals and five animals with ALI produced by the endobronchial instillation of 0.1 N HCl (0.5 ml.kg-1.lung-1). After 2 h, the lymph-to-plasma protein ratio (a measure of microvascular permeability) was increased in the ilea of HCl-injured animals compared with control animals (0.234 +/- 0.03 vs. 0.121 +/ 0.005; P = 0.012) and was accompanied by extensive morphological alterations. Four additional HCl-injured animals were pretreated with an antileukocyte adherence antibody (anti-CD18, 2 mg/kg) that blocked the HCl-induced alterations in the ileum. This study provides evidence for significant systemic organ injury after acid aspiration-induced ALI and suggests that the neutrophil may be a key mediator. PMID- 8514722 TI - AMP deaminase binding in rat skeletal muscle after high-intensity running. AB - Skeletal muscle deaminates a substantial fraction of its adenylate pool to inosine 5'-monophosphate (IMP) when the rate of energy expenditure exceeds supply. How AMP deaminase is activated in vivo is unclear because the substrate affinity is quite low (Michaelis constant approximately 1-2 mM) relative to estimated concentrations of free AMP in skeletal muscle (0.2-1 microM). AMP deaminase:myosin binding causes a large increase in substrate affinity; whether this binding occurs during physiological exercise is uncertain. Exhaustive high speed (60 m/min) treadmill exercise in rats results in an extensive depletion of adenine nucleotide and a stoichiometric accumulation of IMP (1.5-2 mumol/g) in the superficial vastus lateralis muscles (predominantly fast-twitch white). We measured AMP deaminase:myosin binding after intense exercise and found the bound fraction of AMP deaminase to be increased from 9 +/- 1% at rest to 48 +/- 4% at approximately 45 s after exercise. The extent of binding lessened during recovery from exercise, falling to 32 +/- 4% after approximately 75 s and 21 +/- 2% after approximately 105 s. This postexercise dissociation of AMP deaminase from myosin appeared to be a first-order process (approximately 50 s half time). Treadmill running that leads to deamination also results in AMP deaminase:myosin binding. Binding should activate AMP deaminase and thus favor IMP formation at low physiological concentrations of AMP. PMID- 8514723 TI - A mathematical model of the human ventilatory response to isocapnic hypoxia. AB - A mathematical model of the ventilatory response to a period of sustained isocapnic hypoxia in humans has been developed. After a step into hypoxia, there is an initial rapid increase in ventilation (on-transient) followed by a slow decline. At the relief of hypoxia, there is a rapid decrease in ventilation (off transient); the magnitude of this off-transient is smaller than that of the on transient. Previously, the asymmetry between the on- and off-transients has been dealt with by modeling the steps into and out of hypoxia separately. The current objective was to model the whole of the response by allowing the peripheral sensitivity to hypoxia to decline during the sustained exposure to hypoxia. The model was fitted to breath-by-breath data from 20-min periods of hypoxia (end tidal oxygen 50 Torr) at two different levels of end-tidal carbon dioxide tension from five subjects. The model was able to describe the features of the ventilatory changes well, including the slow decline and the asymmetry. PMID- 8514724 TI - Estimation of ventilatory capacity during submaximal exercise. AB - There is presently no precise way to determine ventilatory capacity for a given individual during exercise; however, this information would be helpful in evaluating ventilatory reserve during exercise. Using schematic representations of maximal expiratory flow-volume curves and individual maximal expiratory flow volume curves from four subjects, we describe a technique for estimating ventilatory capacity. In these subjects, we measured maximal expiratory flow volume loops at rest and tidal flow-volume loops and inspiratory capacity (IC) during submaximal cycle ergometry. We also compared minute ventilation (VE) during submaximal exercise with calculated ventilatory maxima (VEmaxCal) and with maximal voluntary ventilation (MVV) to estimate ventilatory reserve. Using the schematic flow-volume curves, we demonstrated the theoretical effect of maximal expiratory flow and lung volume on ventilatory capacity and breathing pattern. In the subjects, we observed that the estimation of ventilatory reserve with use of VE/VEmaxCal was most helpful in indicating when subjects were approaching maximal expiratory flow over a large portion of tidal volume, especially at submaximal exercise levels where VE/VEmaxCal and VE/MVV differed the most. These data suggest that this technique may be useful in estimating ventilatory capacity, which could then be used to evaluate ventilatory reserve during exercise. PMID- 8514725 TI - Cell and sarcomere contractile performance from the same cardiocyte using video microscopy. AB - The relationship between whole cell and sarcomere contractile performance from within the same myocyte remains unclear. In the present study, the dynamic properties of whole cell and sarcomere contractile performance were examined from the same myocyte by computer-assisted video microscopy. Isolated canine left ventricular myocytes were field stimulated at 1 Hz, and whole cell and sarcomere contractile performance was measured in the unloaded unattached state (n = 16) and after attachment to a basement membrane substrate (n = 18). Whole cell and sarcomere contractile measurements were obtained immediately on initiation of electrical stimulation as well as at steady state, after which measurements were repeated in the presence of 25 nM isoproterenol. Video-microscopic images of whole cell and sarcomere contractions were obtained at final magnifications of x1,100 and x5,500, respectively. By use of a 240-Hz high-scan-rate charge-coupled device camera and a video-based edge-detection system synchronized with the camera video output, the myocyte and sarcomere motion data were digitized. Steady state percentage and velocity of shortening for whole cells and sarcomeres were 4.75 +/- 0.30% and 56.50 +/- 2.37 microns/s and 8.63 +/- 0.60% and 2.24 +/- 0.46 microns/s, respectively, for the attached myocytes and 8.63 +/- 0.48% and 71.38 +/- 6.14 microns/s and 11.73 +/- 3.22% and 2.72 +/- 0.62 microns/s, respectively, for the unattached myocytes. With the initiation of electrical stimulation, the extent of the shortening-velocity of relengthening relationship increased in a linear fashion for the attached (whole cell, r = 0.87; sarcomere, r = 0.90; both P < 0.001) and unattached myocytes (whole cell, r = 0.83; sarcomere, r = 0.88; both P < 0.001). In all experiments, isoproterenol significantly increased the slope of these linear relationships (P < 0.01). Furthermore, the relationship between whole cell and sarcomere velocity of shortening was highly linear (r > 0.91, P < 0.001). In summary, this study demonstrated that the video-based edge detection technique could be adapted to measure cell and sarcomere contractile performance from the same myocyte. Furthermore, a significant linear relationship exists between whole cell and sarcomere contractile dynamics with alterations in both load and inotropic state. PMID- 8514726 TI - NMR and analytic biochemical evaluation of CrP and nucleotides in the human calf during muscle contraction. AB - This study compared biochemical and 31P-nuclear magnetic resonance (NMR) determinations of energy metabolites during isometric contractions of the human calf muscle at various exercise intensities. Seven male subjects performed one legged isometric contractions at a work load of 28, 64, and 90% of maximal voluntary contraction force (28-, 64-, and 90%-CON, respectively) for 3 min, 40 s, and 40 s, respectively, in a magnet and in an exact model of the magnet with an arrangement for rapid muscle biopsy sampling from the gastrocnemius. The decrease in phosphocreatine (CrP) determined by NMR was 20, 33, and 71% for 28%-, 64%-, and 90%-CON, respectively. These decreases were the same as those determined biochemically (25, 34, and 61%, respectively). Muscle CrP 1 min after 90%-CON was also found to be similar between NMR and biochemical determinations (88 and 74% of resting value, respectively). Although no significant change in muscle ATP was found by NMR, a decrease of 29% was observed biochemically at 90% CON. The ratio between muscle CrP and ATP was the same between NMR and biochemical determinations except for 90%-CON (1.98 and 0.78, respectively). The increase in muscle ADP determined by NMR was two-, five-, and eightfold higher than that found biochemically for 28%-, 64%-, and 90%-CON, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514727 TI - Heat flux transducer measurement error: a simplified view. AB - Heat flux transducers (HFTs) provide a simple and direct measurement of body heat exchange. Regrettably, HFTs perturb the heat flux at the measurement site, resulting in underestimations of the true heat flux. Equations to correct the discrepancy are available, but most require high-precision temperature measurements above and/or below the transducer and/or deep within the body tissues. Because this is not always feasible, the equations are of limited practical benefit. A theoretical basis for the magnitude of the correction factor in relation to the thermal resistances of the materials both above and below the HFT has been developed and has been verified experimentally. The theory is presented in a graph that can be used to drive the HFT correction factor directly or as a guide to know that heat flux was measured within a certain accuracy. This may obviate the use of complicated procedures and equations to perhaps needlessly apply a small correction factor to HFT data. PMID- 8514728 TI - Subject assignment may have biased exercise results. PMID- 8514729 TI - Crystallization and preliminary X-ray study of Agkistrodon halys blomhoffii phospholipase A2 complexed with a specific inhibitor. AB - Phospholipase A2 from the venom of Agkistrodon halys blomhoffii has been crystallized as a complex with a specific inhibitor, (S)-2-dodecanoyl-amino-3 hexanol-1-phosphoglycol. The complex crystals belong to the hexagonal space group, P6(1)22 (or P6(5)22), with cell dimensions of a = b = 61.13 A, and c = 173.15 A. The diffraction extends to at least 2.3 A resolution. PMID- 8514730 TI - Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of Agkistrodon blomhoffii siniticus. AB - Phospholipase A2 inhibitor (PLI) was purified from the blood plasma of Chinese Mamushi, Agkistrodon blomhoffii siniticus, by sequential chromatography on Sephadex G-200, Mono Q, and Blue-Sepharose CL-6B columns. The purified PLI was a glycoprotein with an apparent molecular mass of 75 kDa and was composed of a single subunit with a mass of about 20 kDa. From the results of a cross-linking experiment, the PLI was found to present as a homotrimer of the subunit. The fundamental properties of A. blomhoffii siniticus PLI were very similar to those of Habu Trimeresurus flavoviridis PLI [Kogaki et al. (1989) J. Biochem. 106, 966 971], although the latter was composed of two homologous subunits, PLI-A and PLI B [Inoue et al. (1991) J. Biol. Chem. 266, 1001-1007]. The amino acid sequence of the subunit of A. blomhoffii siniticus PLI was determined by alignment of the peptides obtained by lysyl endopeptidase digestion or Staphylococcus aureus V8 protease digestion. The subunit was composed of 147 amino acid residues with one residue, Asn103 being N-glycosylated. The molecular weight of its protein portion was calculated to be 16,444 Da. The amino acid sequence of A. blomhoffii siniticus PLI subunit showed about 75% homology to those of T. flavoviridis PLI subunits, and also showed significant homologies to those of the carbohydrate recognition domains of C-type lectins. PMID- 8514731 TI - Gallstone formation in cholestanol-fed mice. AB - We examined the effect of cholestanol (5 alpha-dihydrocholesterol) on cholesterol and bile acid metabolism in BALB/c mice. After feeding 1% cholestanol in the diet for 14 months, gallstones composed of 55% cholesterol and 45% cholestanol developed in 20% of the mice and were associated with mucosal inflammation and serosal vessel thickening of the gallbladder. Cholestanol concentrations increased 42-fold in the serum (0.17 versus 0.004 mg/ml) and 18-fold in the liver (0.55 versus 0.03 mg/g) as compared with control mice, whereas cholesterol declined 20 and 26% in serum and liver, respectively. Hepatic microsomal HMG-CoA reductase activity, reflecting cholesterol synthesis, rose 51% (from 7.2 to 10.9 pmol/mg/min). In contrast, hepatic microsomal cholesterol 7 alpha-hydroxylase activity, the rate-determining enzyme for bile acid synthesis, was severely depressed as compared with control mice (0.9 versus 2.2 pmol/mg/min). Discontinuing cholestanol from the diet for 1 month reduced the elevated serum and liver cholestanol concentrations and restored hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities to normal. These results demonstrate that cholestanol is absorbed, replaces cholesterol in serum and liver, causes increased cholesterol synthesis, but inhibits bile acid synthesis. The combination of increased cholesterol synthesis with decreased bile acid formation promotes gallstone formation in cholestanol-fed mice. PMID- 8514732 TI - Purification, some properties, and primary structure of base non-specific ribonucleases from Physarum polycephalum. AB - Two ribonucleases (RNase Phya and RNase Phyb) were purified to homogeneity on SDS PAGE from the culture filtrate of the fungus Physarum polycephalum. The apparent molecular weights of RNases Phya and Phyb were about 20,000. The pH optima of these two RNases were around 4.5-4.75. The RNases released mononucleotides from RNA in the order of 3'-GMP, 3'-AMP, and 3'-pyrimidine nucleotides. RNase Phya and RNase Phyb have the N-terminal amino acid sequences STSFD--- and KSTSF--, respectively. This finding and the similar amino acid compositions of both RNases indicated that they might share the same protein moiety except for the N-terminus Lys. The complete primary structure of RNase Phyb was determined, mostly by analysis of the peptides generated by trypsin, V8 protease, and lysylendopeptidase digestions. The molecular weight of the protein moiety was 19,704. The locations of four half cystine residues were almost superimposable on those in five known fungal RNase T2 family RNases, but two others were not. The sequence homology between RNase Phyb and five known fungal RNases amounted to 53 59 residues, which are concentrated around the three histidine residues, supposed to form the active site in enzymes of the RNase T2 family. However, the amino acid sequence of RNase Phyb more closely resembles those of plant RNases such as RNases from Nicotiana alata [McClure, B.A. et al. (1989) Nature 342, 955-957], tomato [RNase Le, Yost et al. (1991) Eur. J. Biochem. 198, 1-6], and Momoridica charantia [RNase MC1, Ide et al. (1991) FEBS Lett. 284, 161-164]. PMID- 8514733 TI - Endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I, from bovine spleen. AB - By employing various synthetic substrates, as well as soluble denatured protein substrate (TAP-lysozyme) and its derivatives, endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I [EC 3.4.14.1], from bovine spleen was investigated. Cathepsin C efficiently degraded Z-Phe-Arg-MCA, Pro-Phe-Arg-MCA, and Suc-Leu-Leu-Val-Tyr-MCA. This endopeptidase activity required sulfhydryl reagents and halide ions, as in the case of the dipeptidyl aminopeptidase (DAP) activity. We confirmed that this endopeptidase activity is due to cathepsin C itself based on the results on gel-filtration and anion-exchange chromatographies, comparative studies of the inhibitory effects of leupeptin and E-64 on this activity and those of cathepsins B and L, and further the competitive inhibitions by mutual substrates for the DAP and endopeptidase activities of cathepsin C. We also found that cathepsin C endopeptidase activity towards TAP-lysozyme and its N-alpha-acetylated tryptic peptides showed marked dependence on sulfhydryl reagents and chloride ion. Thus, we concluded that cathepsin C has endopeptidase activity as well as DAP activity. The binding energy between the enzyme and the amino acid side chains of the substrate may be as important for the endopeptidase activity as is the electrostatic interaction between the enzyme and the free alpha-amino group of the substrate for the DAP activity. PMID- 8514734 TI - Rabbit plasma alpha-1-antiproteinase S-1: cloning, sequencing, expression, and proteinase inhibitory properties of recombinant protein. AB - A cDNA clone coding for the isoform S-1 of alpha-1-antiproteinase (also called alpha-1-proteinase inhibitor or alpha-1-antitrypsin) was isolated from rabbit liver cDNA library and sequenced. The cDNA consists of 1,426 nucleotides including 5' and 3' noncoding regions and codes for 413 amino acid residues including a signal peptide of 24 residues. The nucleotide and deduced amino acid sequences show 95.5 and 95.2% homologies, respectively, with the F isoform which occurs more abundantly in the rabbit serum than the S isoform. Of the 20 amino acid differences between the two isoforms, nine are located in a stretch of 15 amino acids encompassing the reactive site region, suggesting that these genes have diverged from each other by a nonrandom mechanism. A hypothesis is proposed that the domestication of animal is responsible for the extremely high evolutionary rate in the serpin reactive site region. Prokaryotic expression plasmids were constructed from the cDNA, transfected into Escherichia coli, and expressed. Partially purified recombinant protein inhibited elastase, but did not inhibit trypsin when a small substrate was used. The recombinant S-1 form, however, protected trypsin from inactivation by soybean trypsin inhibitor, a property characteristic of alpha-macroglobulins or rodent murinoglobulins. It is known that there are two types of interaction between serpin and proteinase: (i) most serpins form a stable equimolar complex with the enzyme, resulting in the enzyme inhibition and (ii) some serpins act as a substrate rather than as an inhibitor, resulting in the loss of inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514735 TI - Metabolism and neurite promoting effect of exogenous sphingosylphosphocholine in cultured murine neuroblastoma cells. AB - Exogenous sphingosylphosphocholine analogues and naturally occurring sphingomyelin stimulated the neurite outgrowth in cultured murine neuroblastoma cell lines, NS-20Y, Neuro2a, and N1E-115, whereas exogenous sphinganine at a non cytotoxic concentration inhibited the neurite outgrowth in NS-20Y and Neuro2a cells. The effect of sphingosylphosphocholine on the neurite outgrowth was reversible, indicating that the extended neurites needed to be maintained by continuous stimulation. The uptake and metabolism of the exogenous [3 3H]sphingosylphosphocholine in pulse and chase experiments suggested that the radioactive ceramide and sphingomyelin, which were detected as major metabolic products, were in a precursor/product relationship. It is thus assumed that the exogenous sphingosylphosphocholine taken up by the cells is first degraded into phosphocholine and sphingosine, of which the latter is rapidly acylated to ceramide then converted to sphingomyelin by phosphocholine transfer. Metabolism of sphingosylphosphocholine through sphingomyelin synthesis in the cells may be associated with neurite outgrowth. PMID- 8514736 TI - Primary structures of platelet aggregation inhibitors (disintegrins) autoproteolytically released from snake venom hemorrhagic metalloproteinases and new fluorogenic peptide substrates for these enzymes. AB - A hemorrhagic protein (60 kDa), HR1B, present in the venom of Trimeresurus flavoviridis is a mosaic protein consisting of an NH2-terminal metalloproteinase domain, a disintegrin (platelet aggregation inhibitor)-like domain, and a unique COOH-terminal Cys-rich domain. Since the gross structures of HR1B and protein precursors of disintegrins, trigramin, and rhodostomin, all of which contain the metalloproteinase domain, are similar, many disintegrins so far detected in snake venoms are assumed to be autoproteolytic fragments released from precursors. In ongoing related experiments, the newly purified hemorrhagic metalloproteinases, HR1A from T. flavoviridis venom and HT-1 from Crotalus ruber ruber venom, in addition to HR1B, were autoproteolyzed, in the absence of Ca2+, at 37 degrees C for 3-12 h. Under these conditions, HR1A, HR1B, and HT-1 each released a single major fragment of 32, 34, and 31 kDa, respectively. The entire amino acid sequences of the isolated fragments indicated the presence of disintegrin-like and Cys-rich domains in the COOH-terminal regions of HR1A, HR1B, and HT-1, respectively. It seems likely that so-called disintegrins probably originate from various metalloproteinases present in venom. On the bases of peptide sequences close to the autoproteolytic cleavage sites of these metalloproteinases and the sites of fibrinogen cleaved by these enzymes, we synthesized new intramolecularly quenched fluorogenic peptide substrates. Among the 10 peptides tested, 2 aminobenzoyl (Abz)-Ser-Pro-Met-Leu-2,4-dinitroanilinoethylamide (Dna) proved to be the best substrate for venom metalloproteinase, as deduced from kinetic analyses. PMID- 8514737 TI - The role of HDL consisting of SP-40,40, apo A-I, and lipids in the formation of SMAC of complement. AB - Soluble membrane attack complex (SMAC, SC5b-9) of complement contained apolipoprotein A-I (apo A-I) and lipids. Since SC5b-9 contained no apolipoprotein A-II (apo A-II), the incorporation of apo A-I and lipids into SC5b-9 was not caused by a non-specific binding of high-density lipoprotein (HDL). The incorporation of apo A-I into SC5b-9 was confirmed by a double agar diffusion immuno-assay. SC5b-9 contained one molecule of apo A-I and 3.5% lipids by weight. The composition of the lipids was phospholipid: total cholesterol: triglyceride = 47.5:45.0:7.5, and the ratio of free cholesterol:esterified cholesterol was 22.3:77.7. Since SC5b-7 contained apo A-I and SC5b-9 free of SP-40,40 contained no apo A-I, the HDL consisting of SP-40,40, apo A-I, and lipids was incorporated into SMAC at the stage of SC5b-7 via SP-40,40 as a binding site. PMID- 8514738 TI - Postnatal change of pig intestinal ganglioside bound by Escherichia coli with K99 fimbriae. AB - Enterotoxigenic Escherichia coli possessing K99 fimbriae (E. coli K99) causes diarrhea in piglets of less than 1 week old. The first stage of the bacterial infection is adhesion by the fimbriae on the small intestinal mucosa and the adhesion is followed by colony formation. K99 fimbriae bind specifically to N glycolylneuraminyl-lactosyl-ceramide, GM3(NeuGc) [Ono, E. et al. (1989) Infect. Immun. 57,907-911]. We examined the postnatal change of the content and the molecular species of GM3(NeuGc) in the small intestinal mucosa of 0- to 14-day old piglets and adult pigs. GM3(NeuGc) was a major ganglioside of piglet intestinal mucosa. GM3(NeuGc) content was maximal at birth and gradually decreased to 1/16 in adult animals (5 months old). The ceramide moiety of piglet intestinal GM3(NeuGc) was characterized by the presence of 2-hydroxylated palmitic acid. 125I-labeled bacteria strongly bound to GM3(NeuGc) containing 2 hydroxylated palmitic acid and phytosphingosine compared with GM3(NeuGc) containing any other ceramide moiety. The time when this particular GM3(NeuGc) appears coincides with the time that the infection occurs, and it may explain the susceptibility of newborn piglets to E. coli K99 infection. PMID- 8514739 TI - HD4, a 180 kDa bullous pemphigoid antigen, is a major transmembrane glycoprotein of the hemidesmosome. AB - Hemidesmosomes (HDs) constitute a major cellular apparatus for substratum adhesion in stratified and complex epithelia. A large number of components participate in their construction. HD4, a 180 kDa polypeptide, which is one of the major constituents of the isolated HD fraction, has been suggested to be a glycoprotein, is probably identical to the 180 kDa bullous pemphigoid (BP) antigen [Owaribe, K., Nishizawa, Y., & Franke, W.W. (1991) Exp. Cell Res. 192, 622-630]. By using a sensitive method for detection of glycoproteins, HD4 was confirmed to be a major glycoprotein in cytoskeletal fractions of certain cultured epithelial cells as well as in the HD fraction. To further characterize HD4, we prepared two groups of monoclonal antibodies (mAbs), one recognizing extracellular parts of the HD4 molecule (group I) and the other recognizing intracellular ones (group II). In cultured keratinocytes, type I mAbs, as well as BP autoantibodies that recognize both 230 and 180 kDa polypeptides, stained living cells while type II mAbs did not. The two mAbs exhibited identical staining patterns in fixed cells. HD4 molecules proved partially susceptible to collagenase and Dispase digestion, which removed epitopes of type I mAbs but not those of type II. Immunoelectron microscopy revealed the epitopes of group I mAbs to be localized in the extracellular region of HDs, whereas those of group II were on the cytoplasmic side. These results indicate that the HD4 (BP180) molecule is a major transmembrane glycoprotein with collagen domains in its extracellular portion. PMID- 8514740 TI - Isolation and characterization of a trisialyllactosylceramide, GT3, containing an O-acetylated sialic acid in cod fish brain. AB - An O-acetylated ganglioside that generated a trisialyllactosylceramide or GT3 by base treatment was found for the first time in cod fish brain. This ganglioside was isolated by high-performance liquid chromatography, and characterized by fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy in addition to chemical analysis. The structure was identified as a modified GT3 in which the external sialic acid is O-acetylated at the C-9 position. The chemical structure is as follows: II3(9-O-Ac-NeuAc2-8NeuAc2-8NeuAc2 3)Lac Cer. PMID- 8514741 TI - Ribonuclease multiplicity, diversity, and complexity. PMID- 8514742 TI - Identification of dystrophin-binding protein(s) in membranes from Torpedo electrocyte and rat muscle. AB - Using solubilized dystrophin isolated from torpedo electric tissue and in vitro blot overlay assay, we have identified dystrophin-binding proteins in membranes from Torpedo electrocyte and rat muscle. In acetylcholine receptor-rich membranes from Torpedo marmorata electric tissue, an extrinsic protein of M(r) 52,000, known as the 58-kDa protein (Froehner, S.C. (1984) J. Cell Biol. 99, 88-96), represents the major binding site for dystrophin. When membranes were solubilized by non-ionic detergents, the 52-kDa protein as well as a few proteins of M(r) 200,000, 87,000, and 45,000 co-extract and copurify with dystrophin. In rat sarcolemma, a protein doublet of approximately 58-60 kDa also binds dystrophin in vitro, this protein likely being the DAP 59 characterized by Ervasti and Campbell (Ervasti, J. M., and Campbell, K. P. (1991) Cell 66, 1121-1131). We postulate that the 52- and 59-kDa proteins are functional homologs that play the role of "receptors" for dystrophin in various specialized membrane domains. PMID- 8514743 TI - ATPase activity of TyrR, a transcriptional regulatory protein for sigma 70 RNA polymerase. AB - The TyrR protein of Escherichia coli is the chief transcriptional regulator of several genes essential for aromatic amino acid biosynthesis and transport. It was established in previous studies that this protein binds ATP, that the TyrR.ATP complex has enhanced affinity for tyrosine, and that the susceptibility of the TyrR protein to hydrolysis by trypsin is altered by ATP. Here we show that the TyrR protein has ATPase activity, which is stimulated by tyrosine. In this respect the TyrR protein resembles the transcriptional activator NtrC. The NtrC protein contains an internal polypeptide segment, 220 amino acid residues in length, with a high degree of identity to the TyrR protein, that contains the presumptive ATPase catalytic center. PMID- 8514744 TI - Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase. AB - The coding region of the human vasopressin type 2 receptor gene bears mutations in the individuals affected with congenital nephrogenic diabetes insipidus, a disease characterized by the inability of the kidney to concentrate urine in response to vasopressin. Although it is assumed that the mutations result in loss of receptor function, proof of this hypothesis is lacking. We introduced one of these naturally occurring point mutations leading to a single amino acid change (Arg137-->His) into wild type cDNA. The mutant protein was expressed, and the functional properties of the receptor were examined. The mutant receptor exhibited an unaltered binding affinity for vasopressin compared to the wild type but failed to stimulate the Gs/adenylyl cyclase system. These data provide biochemical proof that the mutant receptor is the cause of the disease. PMID- 8514745 TI - Covalent modification with concomitant inactivation of the cAMP-dependent protein kinase by affinity labels containing only L-amino acids. AB - Affinity labels for proteins that process other proteins (e.g. proteinases and protein kinases) are an amalgam of two components, an active site-directed peptide carrier and a non-peptidic electrophilic appendage. We have synthesized several affinity labels for the cAMP-dependent protein kinase that are composed solely of L-amino acids and therefore contain only functionality present in naturally occurring proteins. We have found that 2 adjacent cysteine residues, when covalently linked via a peptide bond and an intramolecular disulfide loop (abbreviated as Cys<-->Cys), serves as a potent electrophile. The peptides Leu Arg-Arg-Cys<-->Cys-Leu-Gly (1), Leu-Arg-Arg-Ala-Cys<-->Cys-Gly (2), and Leu-Arg Arg-Ala-Ala-Cys<-->Cys-Gly (3) inactivate the cAMP-dependent protein kinase in a time-dependent fashion. Since dialysis does not restore activity, but dithiothreitol does, this strongly suggests that covalent modification of the target enzyme has occurred at a cysteine residue. Although there are 2 cysteine moieties contained within the protein kinase, the 14C-acetylated affinity labels modify the enzyme only once. In addition, since ATP blocks inactivation of the protein kinase, this implies that it is the active site cysteine residue (Cys 199) that has undergone covalent modification. Based on the KI(inact) values obtained from inactivation kinetics, we conclude that the optimal site on the affinity label for the electrophilic Cys<-->Cys is 1 amino acid removed from the 2 arginine residues (i.e. 2). In addition, the efficacy of these inhibitors is also dependent upon the size of the disulfide ring. The eight-membered disulfide ring-containing peptides 1-3 are relatively poor affinity labels compared to the 12-membered ring-containing inhibitor, [formula: see text] PMID- 8514746 TI - p53 binds to the TATA-binding protein-TATA complex. AB - Earlier reports show that p53, both wild type and mutants, may affect transcription. Wild-type p53 activates promoters with p53-binding sites while inhibiting promoters without binding sites. Mutant p53, on the other hand, has been shown to activate transcription from specific promoters. These observations suggest that both wild-type and mutant p53 may interact with a general transcription factor(s). In this report, we have shown that the cloned TATA binding protein (TBP) from human and yeast interacts with human p53. TBP co immunoprecipitates with wild-type or mutant human p53 when incubated with the p53 specific monoclonal antibody and Protein A-agarose. Wild-type murine p53 has also been found to interact with human TBP. Protein blot assays have demonstrated that the interaction between p53 and human TBP is direct. By gel retention analysis, we have shown that the complex of TBP and p53 (both wild type and mutant) can bind to the TATA box. The similar qualitative binding capability of wild-type and mutant p53 with human TBP and the similarity of the two complexes in binding to the TATA box suggest that the functional discrimination between wild-type and mutant p53 may not lie in their ability to bind TBP. The nature of the p53.TBP or p53.TBP.TATA complex may determine the success of transcription. PMID- 8514747 TI - 2'-O-methyl RNA oligonucleotides identify two functional elements in the trypanosome spliced leader ribonucleoprotein particle. AB - Using permeable trypanosomes as an in vivo model system for trans-splicing, we have searched for functional elements in the Trypanosoma brucei spliced leader (SL) RNA by masking various regions of the molecule with short antisense 2'-O methyl RNA oligomers. Initial probing of the structure of newly synthesized SL RNA by deoxyoligonucleotide-directed ribonuclease (RNase) H cleavage revealed three accessible regions: the 5' end, sequences downstream of the 5' splice site, and a putative single-stranded sequence between stem-loops II and III, which is thought to be analogous to the mammalian Sm-binding site of U small nuclear RNAs. Using antisense 2'-O-methyl RNA oligomers, two functional elements of the SL RNA became apparent. Masking of positions 1-18 inhibited modification of the cap 4 structure of newly synthesized SL RNA and, thereby, blocked utilization of the SL RNA in trans-splicing. In addition, nucleotides +1 to +4 relative to the 5' splice site, which include the invariant GU dinucleotide were accessible to oligomer binding in the SL ribonucleoprotein particle, and their blockade resulted in complete inhibition of trans-splicing. In contrast, RNA oligomer binding to the single-stranded region between stem-loop II and III of the SL RNA had no detectable effect on trans-splicing activity of the SL RNA. PMID- 8514748 TI - Interleukin-2-dependent transcriptional and post-transcriptional regulation of transferrin receptor mRNA. AB - Interleukin-2 (IL-2) controls the proliferation of the murine T cell line B6.1 and induces transferrin receptor (TfR) mRNA steady-state levels 50-fold when added to arrested, IL-2-deprived cells. In addition, TfR mRNA is post transcriptionally regulated by intracellular iron. Low iron levels activate a cytoplasmic RNA-binding protein, called iron regulatory factor (IRF) or iron responsive element-binding protein, which coordinately stabilizes TfR mRNA and inhibits ferritin mRNA translation. Since ferritin expression is known to be modulated by cytokines, we decided to investigate the mechanism by which IL-2 activates TfR gene expression in B6.1 cells. Induction by IL-2 of both nuclear and cytoplasmic TfR RNA was compared with run-on transcription rates in isolated nuclei. The results revealed a 3-fold increase in TfR gene transcription and a 6 fold rise in nuclear TfR RNA reaching its steady-state level within 2 h. The main accumulation of mature mRNA in the cytoplasm occurred after 6 h in parallel with the activation of IRF. However, stimulation of IRF binding activity by the iron chelator desferrioxamine, in the absence of IL-2, failed to induce TfR mRNA. Moreover, deprivation of growing B6.1 cells of IL-2 resulted in cell arrest and a rapid decay of TfR mRNA, which was not prevented by the activation of IRF with desferrioxamine. TfR mRNA stabilization appears, therefore, to depend on IL-2. We conclude that TfR mRNA expression is controlled by at least three steps at the onset of cell proliferation: (i) the growth factor-dependent activation of transcription; (ii) mRNA stabilization by IRF in the cytoplasm; and (iii) an additional IL-2-dependent activity which prevents TfR mRNA degradation. Our results indicate that expression of TfR, like ferritin, is controlled by both iron and cytokines. PMID- 8514749 TI - Activation of the phosphosignaling protein CheY. I. Analysis of the phosphorylated conformation by 19F NMR and protein engineering. AB - CheY, the 14-kDa response regulator protein of the Escherichia coli chemotaxis pathway, is activated by phosphorylation of Asp57. In order to probe the structural changes associated with activation, an approach which combines 19F NMR, protein engineering, and the known crystal structure of one conformer has been utilized. This first of two papers examines the effects of Mg(II) binding and phosphorylation on the conformation of CheY. The molecule was selectively labeled at its six phenylalanine positions by incorporation of 4 fluorophenylalanine, which yielded no significant effect on activity. One of these 19F probe positions monitored the vicinity of Lys109, which forms a salt bridge to Asp57 in the apoprotein and has been proposed to act as a structural "switch" in activation. 19F NMR chemical shift studies of the labeled protein revealed that the binding of the cofactor Mg(II) triggered local structural changes in the activation site, but did not perturb the probe of the Lys109 region. The structural changes associated with phosphorylation were then examined, utilizing acetyl phosphate to chemically generate phsopho-CheY during NMR acquisition. Phosphorylation triggered a long-range conformational change extending from the activation site to a cluster of 4 phenylalanine residues at the other end of the molecule. However, phosphorylation did not perturb the probe of Lys109. The observed phosphorylated conformer is proposed to be the first step in the activation of CheY; later steps appear to perturb Lys109, as evidenced in the following paper. Together these results may give insight into the activation of other prokaryotic response regulators. PMID- 8514751 TI - The crystallographic structure of the protease from human immunodeficiency virus type 2 with two synthetic peptidic transition state analog inhibitors. AB - The crystal structure of human immunodeficiency virus (HIV) type 2 protease has been determined in complexes with peptidic inhibitors Noa-His-Cha psi [CH(OH)CH(OH)]Val-Ile-Amp (U75875) and Qnc-Asn-Cha psi [CH(OH)CH2]Val-Npt(U92163) (where Noa is naphthyloxyacetyl, Cha is cyclohexylalanine, Amp is 2 aminomethylpyridine, Qnc is quinoline-2-carbonyl, and Npt is neopentylamine), which have dihydroxyethylene and hydroxyethylene moieties, respectively, in place of the normal scissile bond of the natural ligand. The complexes crystallize in space group P2(1)2(1)2(1), with one dimer-inhibitor complex per asymmetric unit and average cell dimensions of a = 33.28 A, b = 45.35 A, c = 135.84 A. Data were collected to approximately 2.5-A resolution. The model structures were refined with resulting R-factors of around 0.19. As expected, the HIV-2 protease structure is approximately C2-symmetric with a gross structure very similar to that of the HIV-1 enzyme. The inhibitors bind in an extended conformation positioned lengthwise in the binding cleft in a manner similar to that found in the HIV-1 protease-inhibitor complexes previously reported. The substitution of the bulkier Ile82 side chain in the HIV-2 protease may help explain the better ability of HIV-2 protease to bind and hydrolyze ligands with small P1 and P1' side groups. It appears that differences in specificity between the proteases of HIV-1 and HIV-2 are not merely a result of simple side chain substitutions, but may be complicated by differences in main chain flexibility as well. PMID- 8514750 TI - Activation of the phosphosignaling protein CheY. II. Analysis of activated mutants by 19F NMR and protein engineering. AB - The Escherichia coli CheY protein is activated by phosphorylation, and in turn alters flagellar rotation. To investigate the molecular mechanism of activation, an extensive collection of mutant CheY proteins was analyzed by behavioral assays, in vitro phosphorylation, and 19F NMR chemical shift measurements. Substitution of a positively charged residue (Arg or Lys) in place of Asp13 in the CheY activation site results in activation, even for mutants which cannot be phosphorylated. Thus phosphorylation plays an indirect role in the activation mechanism. Lys109, a residue proposed to act as a conformational "switch" in the activation site, is required for activation of CheY by either phosphorylation or mutation. The 19F NMR chemical shift assay described in the preceding article (Drake, S. K., Bourret, R. B., Luck, L. A., Simon, M. I., and Falke, J. J. (1993) J. Biol Chem. 268, 13081-13088) was again used to monitor six phenylalanine positions in CheY, including one position which probed the vicinity of Lys109. Mutations which activate CheY were observed to perturb the Lys109 probe, providing further evidence that Lys109 is directly involved in the activating conformational change. Two striking contrasts were observed between activation by mutation and phosphorylation. (i) Each activating mutation generates a relatively localized perturbation in the activation site region, whereas phosphorylation triggers a global structural change. (ii) The perturbation of the Lys109 region observed for activating mutations is not detected in the phosphorylated protein. These results are consistent with a two-step model of activated CheY docking to the flagellar switch. PMID- 8514752 TI - Mannosylphosphoryldolichol-mediated reactions in oligosaccharide-P-P-dolichol biosynthesis. Recognition of the saturated alpha-isoprene unit of the mannosyl donor by pig brain mannosyltransferases. AB - The specificity of Man-P-Dol:Man5-8GlcNAc2-P-P-Dol (Oligo-P-P-Dol) mannosyltransferase activity in pig brain was investigated by comparing a variety of mannosylphosphorylisoprenols as mannosyl donors. For this comparison the beta Man-P-isoprenols were synthesized using a partially purified preparation of mannosylphosphorylundecaprenol (Man-P-Undec) synthase from Micrococcus luteus. The bacterial mannosyltransferase efficiently catalyzed the transfer of mannose from GDP-[3H]Man to a series of defined isoprenyl monophosphate substrates. Two alpha-Man-P-dolichols were synthesized chemically and also examined as substrates. When exogenous beta-[3H]Man-P-Dol95 was tested as a substrate for Man P-Dol:Oligo-P-P-Dol mannosyltransferase activity in pig brain microsomes, [3H]mannose was actively transferred to endogenous Oligo-P-P-Dol acceptors. The major enzymatically labeled product was Man9GlcNAc2-P-P-Dol. Under identical conditions beta-[3H]mannosylphosphorylpolyprenol (Man-P-Poly95) was an extremely poor substrate, indicating that the saturated alpha-isoprene unit of the dolichyl moiety is critical for recognition of the lipophilic mannosyl donor by the endoplasmic reticulum-associated mannosyltransferase(s). When Man-P-dolichols containing 2, 11, or 19 isoprene units were compared, the initial rates for the mannosyl transfer reactions and the affinity of the enzyme(s) for the mannophospholipid substrate increased with the length and hydrophobicity of the polyisoprenol chain. The anomeric configuration of the mannosyl moiety is apparently essential because the brain mannosyltransferases exhibited a strong preference for beta-Man-P-dolichols over the corresponding chemically synthesized alpha-stereoisomers. These results: 1) describe a simple two-step procedure for obtaining a partially purified preparation of Man-P-Undec synthase that efficiently synthesizes a variety of beta-Man-P-isoprenols; 2) indicate that pig brain Man-P-Dol:Oligo-P-P-Dol mannosyltransferase activity is relatively specific for lipophilic mannosyl donors containing 19 isoprene units with a beta-Man 1-P group attached to the saturated alpha-isoprene unit of dolichol; and 3) emphasize the importance of the reduction of the alpha-isoprene unit in the biosynthesis and function of Dol-P in mammalian cells. PMID- 8514753 TI - Activation of mutant forms of DnaA protein of Escherichia coli by DnaK and GrpE proteins occurs prior to DNA replication. AB - Mutant forms of DnaA protein, inert in a replication system composed of other purified proteins, are "activated" by DnaK and GrpE heat shock proteins (Hupp, T. R., and Kaguni, J. M. (1993) J. Biol. Chem. 268, 13137-13142). The effect of these heat shock proteins on DnaA5 and DnaA46 protein was separated from the event of DNA synthesis by incubation in two stages. Components necessary during the first stage for "activation" included GrpE and DnaK proteins, ATP at 0.2 mM or greater, and polyvinyl alcohol (8%) or glycerol, optimal at concentrations between 20 and 30%. An ATP regenerating system provided by creatine kinase and creatine phosphate was stimulatory. Addition of the activated form of DnaA5 or DnaA46 protein to a reconstituted system containing other purified replication proteins during the second stage of incubation resulted in DNA replication. Activation of DnaA5 or DnaA46 protein by heat shock proteins was thermolabile, suggesting that the temperature sensitivity of dnaA5 and dnaA46 mutants is related to this thermolabile interaction. A third heat shock protein, DnaJ protein, interfered with the activation of DnaA5 protein if present during the first stage of incubation. This inhibitory effect was less striking if included during the second stage of incubation. These results suggest a mechanism for regulation of the activity of DnaA protein. PMID- 8514754 TI - Features of the spermidine-binding site of deoxyhypusine synthase as derived from inhibition studies. Effective inhibition by bis- and mono-guanylated diamines and polyamines. AB - Several types of basic compounds structurally related to spermidine, one of the substrates for deoxyhypusine synthase, were tested as inhibitors of this enzyme. The results indicate that inhibitory compounds associate with the enzyme at the site of spermidine binding and must possess two charged primary amino or guanidino groups, or one of each. The efficiency of inhibition is related to the maximum possible distance between the primary amino groups and is adversely affected by substitutions on the secondary amino group or in the carbon chains of polyamines. The mono-guanyl derivatives are much more effective inhibitors than the parent amines or their bis-guanylated counterparts, N1-guanyl-1,7 diaminoheptane being the most effective compound with a Ki value of about 10 nM. Based on these observations we have proposed a model for the spermidine-binding site of deoxyhypusine synthase. Studies with Chinese hamster ovary cells reveal a direct correlation between prevention of hypusine formation by several guanyldiamines and their in vitro inhibition of deoxyhypusine synthase. This evidence for disruption of the initial step in the post-translational maturation of eukaryotic initiation factor 5A provides a basis for the potential control of protein biosynthesis and cell proliferation. PMID- 8514755 TI - Determination of creatine kinase kinetic parameters in rat brain by NMR magnetization transfer. Correlation with brain function. AB - The pseudo first-order rate constant kf of the creatine kinase (CK) forward reaction as well as the CK forward flux FCK,f have been shown to correlate better with cardiac performance than the steady-state levels of ATP and PCr (Bittl, J. A., and Ingwall, J. S. (1985) J. Biol. Chem. 260, 3512-3517). In order to elucidate the relationship between the CK kinetic parameters and brain activity, we have determined, using the non-invasive NMR technique of magnetization transfer, kf and FCK,f in rats, in which brain activity was experimentally varied by administration of either thiopental sodium or bicuculline to decrease or increase electro-encephalogram (EEG) intensity, respectively. The steady-state levels of ATP and PCr, as well as the accumulation of deoxyglucose 6-phosphate (DG-6P) in brain following intraperitoneal administration of deoxyglucose, were determined simultaneously by the NMR technique, whereas the cortical EEG was recorded in a separate experiment. The EEG intensity (range, 1-20 Hz), taken as a measure for brain performance, as well as the amount of DG-6P formed in brain, reflecting the synthesis rate of high energy phosphates (ATP and PCr), linearly correlated with kf. Despite large changes in both EEG intensity (50-250%) and kf (0.12-0.69 s-1) between thiopental sodium- and bicuculline-treated rats, the ATP levels remained constant, whereas the PCr levels decreased with high EEG activity. In contrast to the expectation based on model calculations of CK kinetics, the PCr levels did not increase above control values at reduced EEG intensity (50% of controls). At EEG intensities exceeding control values (bicuculline-treated rats) FCK,f increased as predicted by CK equilibrium. In conclusion, we have shown that in the rat brain, like in the heart, the CK forward rate constant kf, in contrast to ATP and PCr levels, is a sensitive reliable indicator of both increased and reduced function. PMID- 8514756 TI - Structural mapping of catalytic site with respect to alpha-subunit and noncatalytic site in yeast mitochondrial F1-ATPase using fluorescence resonance energy transfer. AB - The intrinsic tryptophan fluorescence of Schizosaccharomyces pombe mitochondrial F1 is a very sensitive probe to differentiate nucleotide binding to catalytic and noncatalytic sites (Divita, G., Di Pietro, A., Roux, B., and Gautheron, D. C. (1992) Biochemistry 31, 5791-5798), the catalytic site saturation producing quenching of Trp-257 fluorescence (Divita, G., Jault, J.-M., Gautheron, D. C., and Di Pietro, A. (1993) Biochemistry 32, 1017-1024). The present results indicate that two types of fluorescent nucleotide analogues, bearing either 2'(3')N-methylanthraniloyl (mant) or 2',3'-O-(2,4,6-trinitrophenyl) (TNP) group, exhibit high-affinity binding and behave similarly to the corresponding unmodified nucleotides. Selective binding of mant GDP to the catalytic site produces a marked quenching of intrinsic fluorescence which is due to resonance energy transfer between Trp-257 and the mant group. The high efficiency of the transfer allows the determination of a short distance, 10.5 A, indicating the close proximity of catalytic site and alpha-subunit Trp-257. Selective saturation of the noncatalytic site by TNP-ADP produces a marked quenching of the extrinsic fluorescence of mant GDP bound to the catalytic site, which is correlated to an important resonance energy transfer between the two fluorescent groups. A rather short distance of 17.5 A is calculated, indicating vicinity of catalytic and noncatalytic sites. PMID- 8514757 TI - The cyclophilin component of the unactivated estrogen receptor contains a tetratricopeptide repeat domain and shares identity with p59 (FKBP59). AB - Using a rapid single-step affinity chromatography procedure we have isolated the unactivated estrogen receptor from bovine uterus. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western analyses for protein extracts recovered from affinity chromatography of receptor cytosols, either preincubated or untreated with estradiol, suggest a component structure for the intact oligomeric receptor which includes hsp90, hsp70, p59, a 40-kDa cyclophilin related protein, and an uncharacterized 22-kDa protein species. We have chemically determined the amino acid sequences of eight peptides derived from the 40-kDa component and now report the cloning and primary sequence of a cDNA encoding this protein, which is designated estrogen receptor-binding cyclophilin (ERBC). Homology analyses confirm that ERBC is a new member of the cyclophilin family and contains a C-terminal domain with significant sequence homology to an internal region of p59, a binding protein for the immunosuppressant FK506 (FKBP59). This conserved region includes a 3-unit tetratricopeptide repeat domain bounded at the C terminus by a putative calmodulin binding site. We propose that the tetratricopeptide repeat domain mediates the protein interaction properties of ERBC and p59. Both immunophilins may have important roles in receptor assembly and may represent a new category of ligand- and calcium-dependent modulators of protein function. PMID- 8514758 TI - A complex array of double-stranded and single-stranded DNA-binding proteins mediates induction of the ovalbumin gene by steroid hormones. AB - The transcriptional induction of the chicken ovalbumin gene by steroid hormones is abolished by inhibitors of protein synthesis such as cycloheximide, suggesting that a labile protein mediates this process. A steroid-dependent regulatory element (SDRE) has been identified in the 5'-flanking region of the gene between 900 and -780 that is required for induction by steroids. Additional transfection experiments limit the 5'-border of the SDRE to the region between -892 and -864. To investigate whether any of the proteins binding to the SDRE are affected by estrogen or cycloheximide, protein binding was investigated using DNase I and exonuclease III footprinting and gel mobility shift assays. These experiments demonstrate that labile proteins bind to the sequences between -900 and -860 and between -810 and -820. Four oviduct nuclear proteins, including one of the labile proteins, binding to the SDRE prefer single-stranded DNA (ssDNA) in a sequence specific manner. The binding activity of three of these ssDNA-binding proteins is increased in oviduct nuclear protein extracts from estrogen-treated chicks. These data suggest that induction of the ovalbumin gene is mediated by a complex collection of ssDNA- and double-stranded DNA-binding proteins whose activities are in turn regulated by their short half-lives or by estrogen. PMID- 8514759 TI - Characterization of insulin-stimulated seryl/threonyl protein kinases in rat skeletal muscle. AB - Post-insulin receptor signal transduction is mediated by a cascade of seryl/threonyl protein kinases which includes a family of mitogen-activated protein (MAP) kinases, ribosomal protein S6 kinases, and casein kinase-2. Previous studies have characterized these kinases primarily in cultured or isolated cells. We have demonstrated that intravenous injection of insulin into fasted rats significantly stimulated the activities of MAP kinases and S6 kinases in skeletal muscle, independently of the blood glucose levels in these animals. Anion exchange chromatography on Mono Q afforded the resolution of at least five peaks of insulin-stimulated myelin basic protein kinase activity. By immunological criteria, these myelin basic protein kinases included the p42mapk and p44erk1 as well as other potentially novel 44-kDa MAP kinases. Insulin activated ribosomal S6 kinases were resolved into two major peaks by Mono Q chromatography, the latter of which contained a 100-kDa isoform of p90rsk as revealed by immunoblotting with an anti-rsk-peptide antibody. A 32-kDa S6 kinase in the earlier peak may represent a novel protein kinase in this tissue. Skeletal muscle casein kinase-2 was not significantly stimulated following insulin injection into rats under our experimental conditions. These results indicate that the intact rat can serve as a useful model system to investigate the mechanisms of insulin signal transduction. PMID- 8514760 TI - Biphasic effects of cytosolic Ca2+ on Ins(1,4,5)P3-stimulated Ca2+ mobilization in hepatocytes. AB - The increase in cytosolic free Ca2+ concentration that follows mobilization of intracellular Ca2+ stores by inositol 1,4,5-trisphosphate Ins(1,4,5)P3 has been reported to modulate the sensitivity of Ins(1,4,5)P3 receptors. We have examined the effects of cytosolic Ca2+ on Ins(1,4,5)P3-stimulated Ca2+ mobilization in permeabilized hepatocytes. Increasing the free Ca2+ concentration in the medium ([Ca2+]m) caused a concentration-dependent increase in the sensitivity of the stores to Ins(1,4,5)P3; the concentration of Ins(1,4,5)P3 that caused half maximal Ca2+ mobilization (EC50) decreased from 261 +/- 11 nM (n = 3) to 50 +/- 4 nM (n = 8) as [Ca2+]m was increased from approximately 7 nM to 1.6 microM. The EC50 for this effect of Ca2+ was approximately 250 nM. In addition, higher [Ca2+]m (> 600 nM) reduced the extent of Ca2+ release induced by a maximal concentration of Ins(1,4,5)P3; elevating [Ca2+]m to 2.6 microM reduced the proportion of Ca2+ releasable by Ins(1,4,5)P3 by 94 +/- 8% (n = 3). Both effects of Ca2+ were independent of Ca2(+)-stimulated Ins(1,4,5)P3 formation. When elevated [Ca2+]m was returned to control levels, the sensitization of Ins(1,4,5)P3-mediated Ca2+ mobilization reversed completely, whereas the reduction in the size of the Ins(1,4,5)P3-sensitive Ca2+ pool was reversed by only 59 +/- 12% (n = 5) after 20 s and was not further reversed after 100 s. The two distinct effects of Ca2+ on Ins(1,4,5)P3-mediated Ca2+ release combined to control the amount of Ca2+ released by a submaximal concentration of Ins(1,4,5)P3 in a biphasic manner. PMID- 8514761 TI - Purification and characterization of the methyltransferase from the type 1 restriction and modification system of Escherichia coli K12. AB - The DNA methyltransferase component of the type I restriction and modification enzyme of Escherichia coli K12 has been purified. The active component, a trimer of molecular mass 170 kDa consisting of one DNA recognition subunit (S) and two modification subunits (M), showed the expected preference for modifying a hemimethylated substrate rather than an unmethylated one. Small amounts of the dimers M2 and M1S1 were also isolated. Subunit rearrangements of the three protein species occurred on ion exchange and heparin-agarose chromatography. Denaturation of the trimer gave folding intermediates, and these and the dimer forms isolated during purification may reflect the assembly of the protein in vivo. Enzyme activity was recovered on refolding the denatured protein by dilution of the denaturant. A comparison of the predicted isoelectric points of all known S subunits of type I restriction and modification enzymes revealed values that correlated with the arrangement of type I systems in several families. Electrostatic interactions may explain the different subunit stoichiometries observed during purification of type I enzymes and the differing preferences for hemimethylated DNA displayed by the three type I families. PMID- 8514762 TI - Characterization of neutral glycosphingolipids in human cataractous lens. AB - Neutral glycosphingolipids were purified from human senile cataractous lenses by a combination of solvent extraction, Folch's partition, acetylation, and column chromatography using DEAE-Sephadex and Iatrobeads. Six major glycosphingolipids (A-F) from monohexosylceramide to pentahexosylceramide were identified by sugar composition analysis, methylation analysis, secondary ion-mass spectrometry, glycosidase digestion, and chromium trioxide oxidation. Their structures suggested that they were closely related in their metabolism: their sugar chains were in sequence and their ceramide moieties were similarly composed, namely C16:0 and C24:1 constituted most of the fatty acids, and long-chain base components were mostly C18-dihydrosphingosine with a small portion of C18 sphingosine. The sugar chains implied two pathways branching from lactosylceramide: one to globotriaosylceramide and the other to lactotriaosylceramide, which leads to the production of Le(x) glycolipid via neolacto type 2 core chain. PMID- 8514763 TI - Site specificity of pea histone acetyltransferase B in vitro. AB - Histone acetyltransferase B from pea embryonic axes has been purified approximately 300-fold by a combination of chromatographic procedures, including affinity chromatography on histone-agarose. The enzyme preparation has been used for the in vitro transfer of acetyl groups from [1-14C]acetyl-CoA to non acetylated pea histone H4. Up to three acetyl groups can be introduced into the histone. The resulting mono-, di-, and triacetylated H4 isoforms were separated and sequenced to determine the acetylated sites. Only sites 5, 12, and 16 were used by histone acetyltransferase B, but no clear preference among them was observed. The absence of modification of other potentially acetylatable sites is another indication that acetylation of the different lysine residues in the N terminal H4 tail serves as a specific signal in different nuclear processes. PMID- 8514764 TI - Myosin subfragment 1 inhibits dissociation of nucleotide and calcium from G actin. AB - The dissociation rates of 1,N6-ethenoadenosine 5'-triphosphate (epsilon ATP) and of Ca2+ from G-actin and its complex with myosin subfragment 1 (S1) were measured by recording a large decrease in the fluorescence intensity of the dissociating nucleotide. Under the experimental conditions employed, the binary G-acto-S1A2 complex does not polymerize (Chaussepied, P., and Kasprzak, A. A. (1989) Nature 342, 950-953). The released nucleotide was hydrolyzed either by alkaline phosphatase or by apyrase; to trap Ca2+, EDTA was used. From the anisotropy of N iodoacetyl-N'-(5-sulfo-1- naphthyl)ethylenediamine (1,5-IAEDANS)-actin, it was established that during the dissociation of epsilon ATP, the G-acto-S1 complex remained stable and the equilibrium of the system was unaltered. The reactions followed first order kinetics. The dissociation rate constant, kd for epsilon ATP decreased from 5.5 x 10(-4) s-1 for free G-actin to 1 x 10(-4) s-1 for G-acto S1A2; for Ca2+, kd was also similarly reduced from 2.8 x 10(-2) s-1 to 4 x 10(-3) s-1. Two proteolytically derived actin variants were also examined. For free subtilisin-cleaved actin, kd for epsilon ATP was elevated 2-fold but was almost unchanged for Ca2+. In the complex of the cleaved G-actin with S1A2, kd for both epsilon ATP and for Ca2+ were reduced. The removal of the last 3 amino acids from actin produced a derivative whose behavior in binding to S1, as well as in the kinetics of epsilon ATP and Ca2+ dissociation, was undistinguishable from the unmodified protein. PMID- 8514765 TI - Role of fructose 2,6-bisphosphate in the control of heart glycolysis. AB - The aim of this work was to study whether changes in fructose 2,6-bisphosphate concentration are correlated with variations of the glycolytic flux in the isolated working rat heart. Glycolysis was stimulated to different extents by increasing the concentration of glucose, increasing the workload, or by the addition of insulin. The glycolytic flux was measured by the rate of detritiation of [2-3H]- and [3-3H]glucose. Under all the conditions tested, an increase in fructose 2,6-bisphosphate content was observed. The glucose- or insulin-induced increase in fructose 2,6-bisphosphate content was related to an increase in the concentration of fructose 6-phosphate, the substrate of 6-phosphofructo-2-kinase. An increase in the workload correlated with a 50% decrease in the Km of 6 phosphofructo-2-kinase for fructose 6-phosphate. Similar changes in Km have been observed when purified heart 6-phosphofructo-2-kinase was phosphorylated in vitro by the cyclic AMP-dependent protein kinase or by the calcium/calmodulin-dependent protein kinase. Since the concentration of cyclic AMP was not affected by increasing the workload, it is possible that the change in Km of 6-phosphofructo 2-kinase, which was found in hearts submitted to a high load, resulted from phosphorylation by calcium/calmodulin protein kinase; other possibilities are not excluded. Anoxia decreased the external work developed by the heart, stimulated glycolysis and glycogenolysis, but did not increase fructose 2,6-bisphosphate. PMID- 8514766 TI - The CDC42 homologue from Caenorhabditis elegans. Complementation of yeast mutation. AB - A Caenorhabditis elegans cDNA encoding a homologue of the p21 ras-related CDC42, designated as CDC42Ce, was isolated from a nematode mixed stage cDNA library. The encoded protein of 188 amino acid residues has 85% identity to both human G25K and CDC42Hs and 79 and 76% identity to the yeast CDC42Sp and CDC42Sc proteins, respectively. The CDC42Ce cDNA maps to a position on C. elegans chromosome II in close proximity to lin-26, a cell lineage gene. The CDC42Ce cDNA hybridizes to 2- and 1.5-kilobase mRNAs. Their expression is developmentally regulated with highest levels at the embryonic stage, decreasing progressively during development except for an increase of the more abundant 1.5-kilobase mRNA at the L3 stage. The glutathione S-transferase/CDC42Ce fusion protein expressed in Escherichia coli displays both GTP binding and intrinsic GTPase activities. The GTPase activity of CDC42Ce is moderately stimulated by human n-chimaerin, a GTPase-activating protein for the related p21 rac1. The CDC42Ce protein complements the temperature-sensitive lethal mutation cdc42-1 in yeast Saccharomyces cerevisiae. These data suggest that CDC42Ce is the C. elegans homologue of the yeast CDC42. The developmental expression pattern of mRNA and is biochemical properties of its encoded protein which are closely related to CErac1 suggest that the two p21s might be involved in related biological processes. PMID- 8514767 TI - Allosteric regulation of glycogen synthase in liver. A physiological dilemma. AB - Glycogen synthase catalyzes the transfer of the glucosyl moiety from UDP-glucose to the terminal branch of the glycogen molecule and is considered to be the rate limiting enzyme for glycogen synthesis. However, under ideal assay conditions, i.e. 37 degrees C with saturating concentrations of UDP-glucose and the activator, glucose-6-P, the maximal catalytic activity of glycogen synthase was only 78% of the in vivo glycogen synthetic rate. Using concentrations of UDP glucose and glucose-6-P likely to be present in vivo, the rate was only approximately 30%. This prompted us to reassess a possible role of allosteric effectors on synthase activity. Glycogen synthase was assayed at 37 degrees C using dilute, pH 7.0, buffered extracts, initial rate conditions, and UDP-glucose and glucose-6-P concentrations, which approximate those calculated to be present in total liver cell water. Several allosteric effectors were tested. Magnesium and AMP had little effect on activity. Pi, ADP, ATP, and UTP inhibited activity. When a combination of effectors were added at concentrations approximating those present in cell water, synthase activity could account for only 2% of the glycogen synthetic rate. Thus, although allosteric effectors are likely to be playing a major role in regulating synthase enzymic activity in liver cells, to date, a metabolite that can stimulate activity and/or overcome nucleotide inhibition has yet to be identified. If such a metabolite cannot be identified, an additional or alternative pathway for glycogen synthesis must be considered. PMID- 8514768 TI - Purification and characterization of an autocrine migration factor for vascular smooth muscle cells (SMC), SMC-derived migration factor. AB - Migration of medial smooth muscle cells (SMC) into the intima is a key step in intimal thickening of atherosclerotic tissues. We previously reported that cultured SMC secrete a potent migration factor for SMC, named SMC-derived migration factor (SDMF). We purified this factor to homogeneity from 20 liters of serum-free conditioned medium of cultured rat aortic SMC by sequential heparin Sepharose column, red-Sepharose column, TSK-heparin high performance liquid chromatography (HPLC) column, and Superose 6 HPLC column chromatographies. SDMF was found to be a 58-kDa polypeptide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Reduction by mercaptoethanol caused only a slight decrease in its molecular mass to 53 kDa. Preparative isoelectric focusing revealed that SDMF is a basic protein with a pI of approximately 10. Purified SDMF enhanced the migration of rat SMC dose dependently, its maximal activity being 4 times that of platelet-derived growth factor-BB. In contrast, SDMF did not enhance the migration of endothelial cells from either human umbilical cord vein or rabbit retinal tissue. SDMF had no effect on the proliferation of SMC. These findings suggest that SDMF enhances SMC migration in vascular walls and that the autocrine system of SMC migration contributes to the formation of intimal thickening in atheroma formation. PMID- 8514769 TI - Comparison of the biophysical characteristics of human brain-derived neurotrophic factor, neurotrophin-3, and nerve growth factor. AB - The structural properties of human brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) were studied using sedimentation equilibrium and circular dichroism (CD), fluorescence and Fourier-transform infrared spectroscopies, and compared with those of human nerve growth factor (NGF). Both the far UV CD and infrared spectra indicate that these three proteins have similar, but not identical, secondary structures which contain primarily beta-sheet and irregular structures. NGF appears to contain the most beta-sheet while NT-3 contains a small fraction of alpha-helix. The near UV CD spectra appear to indicate that the three proteins contain disulfide bonds in similar environments, suggesting a resemblance in tertiary structure. The fluorescent tryptophans found in the molecules are relatively solvent exposed, while Trp102 found only in NT-3 is possibly quenched. The fluorescent Trp(s) in NGF are significantly quenched relative to those in the other two neurotrophic factors. Both NT-3 and BDNF have very hydrophilic surfaces at neutral pH, as indicated by a low binding affinity to a hydrophobic probe, anilinonaphthalenesulfonate. Sedimentation equilibrium showed that BDNF, NT-3, and NGF exist as strongly associated dimers in phosphate buffered saline, pH 7.1. Fits of the observed fringe displacements to various association models suggested that the BDNF, NT-3, and NGF samples contain, in addition to the principal dimeric species, some oligomers, and that NT-3 contains a small fraction of incompetent monomer. PMID- 8514770 TI - Evolution of polysaccharide hydrolase substrate specificity. Catalytic amino acids are conserved in barley 1,3-1,4- and 1,3-beta-glucanases. AB - Catalytic amino acid residues in a 1,3-beta-D-glucan 3-glucanohydrolase (EC 3.2.1.39) and a homologous 1,3-1,4-beta-D-glucan 4-glucanohydrolase (EC 3.2.1.73) from barley have been investigated. To identify amino acids responsible for protonation of the glycosidic oxygen during hydrolysis, carbodiimide-mediated labeling of the enzymes with [14C]glycine ethyl ester was performed. This resulted in loss of activity and specific modification of the Glu288 residues in both enzymes. The stoichiometry of labeling was approximately 1:1, and modification was reduced in the presence of substrate analogues. Based on these data, the Glu288 residues are likely to be present at the active sites of the respective enzymes and may represent the catalytic acids in the hydrolytic reaction. The catalytic nucleophiles of the two enzymes were investigated by labeling with specific, mechanism-based epoxyalkyl-beta-oligoglucosides. Amino acid residues Glu232 and Glu231 were identified as the likely catalytic nucleophiles in the 1,3-1,4- and 1,3-beta-glucanases, respectively. Thus the position of the catalytic nucleophile and the putative proton donating amino acids in the two classes of beta-glucan endohydrolases are conserved. The acquisition of distinct substrate specificities in the evolution of these related enzymes may therefore not require the recruitment of novel catalytic amino acids but rather differences in their positioning at the active site and/or changes in substrate binding residues. PMID- 8514771 TI - Processing of two homologous precursors, pro-neuropeptide Y and pro-pancreatic polypeptide, in transfected cell lines expressing different precursor convertases. AB - The processing of two homologous precursors, pro-neuropeptide Y (pro-NPY) and pro pancreatic poly-peptide (pro-PP), was studied in four neuroendocrine cell lines after transfection: CA-77 medullary thyroid carcinoma cells, AtT-20 corticotrope pituitary cells, RIN2A-19 pancreatic endocrine cells, and NB1 neuroblastoma cells. Northern blot analysis indicated that the AtT-20 cells only expressed precursor convertase 3; in contrast, NB1 cells only expressed precursor convertase 2, whereas the RIN2A-19 and CA-77 cells expressed both enzymes. Despite these differences in expression pattern of precursor convertases the four cell lines were, surprisingly, indistinguishable in respect to their processing of pro-PP and pro-NPY. In all four cell lines, pro-NPY was almost completely converted to NPY, and, in all four cell lines, only around 50% of the PP precursor was converted to PP. The relatively poor processing efficiency of pro PP was rather similar to the processing efficiency of the endogenously produced precursors in the respective cell lines, pro-calcitonin (CA-77), proopiomelanocortin (AtT-20), proinsulin (RIN2A-19), and pro-vasoactive intestinal polypeptide (NB1). At least in the CA-77 cells, NPY and PP were apparently sorted to the regulated secretory pathway, as upon stimulation with secretagogue the release of the transfected peptides increased in parallel with the endogenously expressed peptide, calcitonin gene-related peptide. Mutagenesis studies showed that on the N-terminal side of the di-basic processing site, the otherwise important difference in structure between PP and NPY, a proline for glutamine in position 34, was not responsible for the difference in processing efficiency. On the C-terminal side of the processing site, the efficient processing of pro-NPY could not be transferred to pro-PP by exchanging the whole C-terminal domains of the precursors. It is concluded that pro-NPY is processed more efficiently than pro-PP in all neuroendocrine cell lines tested independent on their expression of the two main precursor convertases and that mutagenesis data indicate that the structural element responsible for the efficient processing of pro-NPY is not located on the N-terminal side of the dibasic processing site. PMID- 8514772 TI - Assembly of the U2 small nuclear ribonucleoprotein from Trypanosoma brucei. A mutational analysis. AB - trans-Splicing in trypanosomes requires the functions of U2 and U4/U6 small nuclear (sn) RNPs. We have analyzed protein binding and assembly of the Trypanosoma brucei U2 snRNP, using specific antibodies against U2 snRNP proteins and in vitro reconstitution assays of U2 deletion derivatives and human trypanosome hybrid RNAs. Stable binding of both the U2-specific 40-kDa and the common proteins requires only the 3'-terminal domain (stem-loop IIb, single stranded region, and stem-loop IV), with loop IV providing the critical sequence determinant; stem-loop IV suffices for binding of the 40 kDa-protein, but not of the common proteins; surprisingly, the sequence of the "Sm-analogous" single stranded region between stem-loops IIb and IV is not essential for protein binding. Our mutational analysis further indicates that interactions between common and specific proteins play an important role in the assembly of a stable core complex. Finally, a partially assembled U2 RNP complex could be identified as a kinetic intermediate of U2 snRNP assembly. We propose a model of the domain structure and assembly of the trans-spliceosomal U2 snRNP, which deviates in several aspects from that of the cis-spliceosomal U2 snRNP; these differences may be related to the trans-splicing-specific functions of the trypanosomal U2 snRNP. PMID- 8514773 TI - Characterization of human tissue factor pathway inhibitor variants expressed in Saccharomyces cerevisiae. AB - Human tissue factor pathway inhibitor (TFPI) and three derivatives with deletions of: 1) the complete COOH-terminal third of the polypeptide including the third Kunitz domain, 2) the third Kunitz domain alone, or 3) the penultimate basic COOH terminal region alone were expressed in yeast as secreted products. High expression yield was obtained only with the derivative that lacked both the third Kunitz domain and the penultimate COOH tail (TFPI1-161). The purified short form was heterogeneously glycosylated with a high mannose glycan. The specific activities of the different mutant polypeptides toward FXa.tissue factor.FVIIa in a chromogenic assay were similar to that of TFPI expressed in baby hamster kidney cells, suggesting that correct folding takes place in yeast and that neither the third Kunitz domain nor the COOH-terminal region is required for this activity. However, in a clotting assay the anticoagulant activities of yeast-produced TFPI and the shortened derivative TFPI1-161 were about 5- and 50-fold lower, respectively, than for full-length TFPI from mammalian cells. Clotting assays with purified short form TFPI showed that it acted mainly via inhibition of FVIIa.tissue factor rather than FXa. The anticoagulant activity of short form TFPI was comparable with that of high affinity antibodies toward tissue factor. PMID- 8514774 TI - Methyl esterification of C-terminal leucine residues in cytosolic 36-kDa polypeptides of bovine brain. A novel eucaryotic protein carboxyl methylation reaction. AB - Incubation of cytosolic extracts of bovine brain with S-adenosyl[methyl 3H]methionine results in the predominant [3H]methyl esterification of a 36-kDa polypeptide. This reaction appears to be distinct from any of the three known types of protein carboxyl methylation reactions previously established. We show here that the methylated 36-kDa polypeptide is a component of a cytosolic protein with a native molecular mass estimated at 178 kDa by gel filtration chromatography. The methyl group is not stable on the protein and is lost as [3H]methanol with a half-life of about 180 min at pH 7.0, 37 degrees C. The methyltransferase responsible for this reaction is a cytosolic protein with a native molecular mass of about 40 kDa that is readily separated from the well described protein-L-isoaspartate (D-aspartate) O-methyltransferase (EC 2.1.1.77). The methyl ester linkage is cleaved by carboxypeptidase Y, suggesting that the 36 kDa polypeptide is methylated on its C-terminal carboxyl group. Extensive digestion of gel-purified 3H-methylated 36-kDa polypeptide with trypsin and leucine aminopeptidase results in a radioactive product that co-chromatographs with authentic L-leucine methyl ester in reverse phase high performance liquid chromatography (HPLC), thin layer chromatography, thin layer electrophoresis, and high resolution-sulfonated polystyrene cation-exchange chromatography. Additionally, the o-phthalaldehyde/beta-mercaptoethanol-derived isoindole derivative of the 3H digestion product co-migrates on HPLC with the corresponding isoindole for L-leucine methyl ester. We demonstrate that a similar methylation system is present in yeast Saccharomyces cerevisiae but not in the bacterium Escherichia coli. These results provide evidence for a new type of reversible posttranslational modification reaction that may function to modulate the activities of its methyl-accepting substrates. PMID- 8514775 TI - Assignment of intrachain disulfide bonds in platelet-derived growth factor B chain. AB - Platelet-derived growth factor (PDGF)-BB is a dimeric protein held together by two disulfide bonds involving the 2nd and 4th cysteine residues from the NH2 terminus. To localize the three intrachain disulfide bonds in PDGF, a method was devised that made it possible to cleave PDGF at specific sites. A set of PDGF derivatives in which specific amino acids were mutated to methionine residues was generated. The recombinant proteins, immunoprecipitated from metabolically labeled transfected COS cells, were then subjected to CNBr cleavage and analyzed by SDS-gel electrophoresis under nonreducing conditions. Based on whether the mutated proteins remained in one piece or fell apart after CNBr cleavage, it was possible to deduce the disulfide bond arrangement in the PDGF B-chain; one bond involves the 1st and 6th cysteine residues, another the 3rd and 7th, and the last the 5th and 8th. The latter disulfide bond was found to be dispensable for receptor binding, whereas the former two were found to be essential for the correct folding or stability of the PDGF B-chain. PMID- 8514776 TI - Characterization of a novel pyruvylated carbohydrate unit implicated in the cell aggregation of the marine sponge Microciona prolifera. AB - The species-specific Ca(2+)-dependent reaggregation of dissociated cells of the marine sponge Microciona prolifera is mediated by a large extracellular adhesion proteoglycan. The glycans of this molecule are involved in the interactions of the proteoglycan with itself and with the sponge cells. Monoclonal antibodies against the glycans block the aggregation of sponge cells (Misevic, G. N., Finne, J., and Burger, M. M. (1987) J. Biol. Chem. 262, 5870-5877). Proteoglycan oligosaccharides were prepared by partial acid hydrolysis of the isolated glycans, and their reactivity with the monoclonal antibodies was monitored after linkage to phospholipid and immunostaining of thin layer chromatograms. One major antibody-reactive oligosaccharide was detected and purified by ion-exchange chromatography and high performance liquid chromatography. 1H NMR spectroscopy, fast atom bombardment-mass spectrometry, methylation analysis, and sequential chemical and enzymatic degradation studies indicated the structure [formula: see text] for the oligosaccharide. The depyruvylated derivative of the oligosaccharide did not react with the aggregation-blocking antibody, which indicates that the pyruvate acetal is an essential part of the epitope. PMID- 8514777 TI - Epidermal growth factor induces serine phosphorylation of stathmin in a human colon carcinoma cell line (LIM 1215). AB - Changes in protein phosphorylation in the human colon carcinoma cell line LIM 1215 after stimulation with epidermal growth factor (EGF) have been analyzed by two-dimensional gel electrophoresis and phosphoamino acid analysis. In addition to a number of tyrosine-phosphorylated proteins, a family of small proteins (M(r) 19,000-20,000) is maximally phosphorylated on serine within 5 min of EGF stimulation. One member of the family has been purified by a combination of two dimensional electrophoresis and reversed-phase high performance liquid chromatography and identified by amino acid sequence analysis as stathmin. Although phosphorylation of stathmin has been reported previously in leukemia cells and following stimulation of hemopoietic or lymphoid cells with several mitogenic agents, this is the first report of stathmin phosphorylation in response to EGF. PMID- 8514778 TI - Purification and characterization of calmodulin-dependent protein kinase III from rabbit reticulocytes and rat pancreas. AB - Calmodulin-dependent protein kinase III (CaM kinase III) phosphorylates and thereby inactivates eukaryotic elongation factor-2 (EF-2). This enzyme, purified to homogeneity from either rabbit reticulocytes or rat pancreas, had similar properties: it migrated with an apparent M(r) of 140,000 by gel filtration, was comprised of a major polypeptide of M(r) 95,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis and had a high affinity for CaM (half-maximal activation < 1 nM). The M(r) 95,000 polypeptide was autophosphorylated by an intramolecular mechanism on seryl residues in the presence of Ca2+, CaM, and ATP, and phosphopeptide mapping indicated that several sites were phosphorylated. Autophosphorylation of CaM kinase III resulted in the generation of a partially Ca2+/calmodulin-independent activity. The enzyme could also be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. Amino acid sequencing of CaM kinase III indicated that it is distinct from other known proteins including the heat-shock protein hsp90, which was recently suggested to be identical to CaM kinase III (Nygard, O., Nilsson, A., Carlberg, U., Nilsson, L., and Amons, R. (1991) J. Biol. Chem. 266, 16425-16430). Furthermore, hsp90 did not copurify with CaM kinase III, and the M(r) 95,000 protein did not cross-react with antibodies to hsp90. CaM kinase III exhibited Michaelis-Menten kinetics toward its substrates ATP and EF-2, with Km values of 15 and 2 microM, respectively. CaM kinase III was able to phosphorylate yeast EF-2 with an Km of 2 microM, but the enzyme did not significantly phosphorylate a variety of other substrates, confirming its identification as a novel protein kinase. PMID- 8514779 TI - Tyrosyl phosphorylation and growth factor receptor association of the human corkscrew homologue, SH-PTP2. AB - The pivotal role of tyrosine kinases in signal transduction is well established, but the role of tyrosine phosphatases remains obscure. The discovery of src homology 2 domain-containing protein tyrosine phosphatases suggested roles for these molecules in growth factor signaling pathways, since src homology 2 domains direct association of downstream signaling molecules with activated growth factor receptors and other phosphotyrosyl proteins. We have found that SH-PTP2, a putative homologue of Drosophila corkscrew, associates in vivo with the ligand activated epidermal growth factor and platelet-derived growth factor receptors. The N-terminal src homology 2 domain of SH-PTP2 directly associates with activated receptors. SH-PTP2 itself is a phosphoprotein, and it becomes tyrosyl phosphorylated upon growth factor activation. These findings suggest several possible models for SH-PTP2 signaling. PMID- 8514780 TI - Molecular cloning and characterization of a rat homolog of CAP, the adenylyl cyclase-associated protein from Saccharomyces cerevisiae. AB - We have isolated a rat cDNA whose expression suppresses the physiological consequences of the chromosomal disruption of CAP, the gene encoding the adenylyl cyclase-associated protein of Saccharomyces cerevisiae. Yeast CAP is a bifunctional protein: the NH2 terminus is necessary and sufficient for cellular responsiveness to activated RAS proteins, while the COOH terminus is required for normal cellular morphology and growth control. The rat MCH1 cDNA encodes a protein of 474 amino acids that is 36% identical to S. cerevisiae CAP and is capable of suppressing the loss of the COOH-terminal functions of CAP when expressed in yeast. The MCH1 protein therefore appears to be a structural and functional homolog of the yeast cyclase-associated proteins. Northern analysis of MCH1 gene expression shows it to be constitutively expressed in all cell and tissue types examined. The cloning of a rat homolog of CAP, in addition to the cloning of a human CAP homolog by Matviw et al. (Matviw, H., Yu, G., and Young, D. (1992) Mol. Cell. Biol. 12, 5033-5040), demonstrates that both cyclase associated proteins and their functions may have evolved with mammalian cells. PMID- 8514781 TI - Structural characterization of a molybdopterin precursor. AB - Purification and structural characterization of a novel pterin that is the immediate biosynthetic precursor for molybdopterin formation in Escherichia coli has been accomplished. The precursor is purified from acid extracts of cells of the Escherichia coli molybdopterin-deficient mutant chlN by reverse phase and ion exchange high performance liquid chromatography. Under a variety of conditions, this precursor oxidizes directly to the previously characterized pterin, compound Z (Johnson, J. L., Wuebbens, M. M., and Rajagopalan, K. V. (1989) J. Biol. Chem. 264, 13440-13447). Like, molybdopterin, the precursor is an oxygen-sensitive, 6 alkyl pterin with a 4-carbon phosphorylated side chain. Analysis by 31P NMR indicates that the precursor phosphate is bound in diester linkage to C-2' and C 4' of the side chain to form a 6-membered ring. The precursor does not contain either of the sulfurs present in molybdopterin, and reduction with sodium borohydride yields a C-1' hydroxyl function. Two-electron oxidation of the precursor results in stoichiometric production of the fully oxidized compound Z. Liquid chromatography-mass spectroscopy of the precursor yields an MH+ ion with a mass of 346, corresponding to a structure for the precursor which is a dihydro form of compound Z. PMID- 8514782 TI - The biosynthesis of molybdopterin in Escherichia coli. Purification and characterization of the converting factor. AB - Molybdopterin, the universal component of the pterin molybdenum cofactors, contains a dithiolene group serving to bind Mo. Addition of the dithiolene sulfurs to a molybdopterin precursor requires the activity of the converting factor. Active converting factor has been purified from Escherichia coli chlA1 cells and found to have two subunits of mass 10 and 16 kDa. Electrophoresis of the purified converting factor on denaturing polyacrylamide gels revealed the presence of a 27-kDa protein as well. Partial NH2-terminal amino acid sequencing showed that the 27-kDa protein is a covalent complex of the 10- and 16-kDa proteins. The inactive converting factor purified from E. coli chlN contains both subunits, as established by amino acid sequencing of the purified material, but the 10-kDa subunit is inactive. Absence of the 27-kDa complex in chlN preparations showed that the inactive covalent complex is only formed from the active converting factor. Evidence that activation of the small subunit requires the acquisition of sulfur was obtained from the difference in the molecular masses of the 10-kDa proteins isolated from chlA1 and chlN cells and from the differential sensitivities of the chlA1 and chlN converting factors to iodoacetamide. PMID- 8514783 TI - In vitro synthesis of molybdopterin from precursor Z using purified converting factor. Role of protein-bound sulfur in formation of the dithiolene. AB - The pterin component of the molybdenum cofactor, termed molybdopterin, is synthesized in Escherichia coli by enzymes encoded at the chl loci. A late step in the biosynthetic pathway, the conversion of a molybdopterin intermediate, precursor Z, to molybdopterin, requires the activity of a two-subunit protein, the converting factor. Precursor Z has many of the features of molybdopterin but lacks the dithiolene function essential for molybdenum ligation. Conversion of precursor Z to molybdopterin is accomplished by transfer of sulfur to produce the dithiolene. The present study describes an in vitro system for molybdopterin biosynthesis comprised of purified precursor Z and purified converting factor. It is established that these components are sufficient to yield molybdopterin, identified by conversion to its characteristic products, Form A, Form B, and dicarboxamidomethylmolybdopterin. Under conditions of precursor excess, the formation of molybdopterin was stoichiometric with converting factor, as would be expected in the absence of a sulfur-regenerating system. The labile product of the reaction, molybdopterin, remained associated with the converting factor large subunit. These results establish that the source of sulfur for molybdopterin biosynthesis is the converting factor and suggest that in vivo a novel sulfur cycle must function to resupply sulfur to the converting factor. PMID- 8514784 TI - Structure and function of the intracellular portion of the mouse interleukin 1 receptor (type I). Determining the essential region for transducing signals to activate the interleukin 8 gene. AB - The structural and functional relationships of the intracellular portion of mouse interleukin 1 receptor (muIL-1R) type I were examined with regard to activation of the human IL-8 gene in the Jurkat T cell line. C-terminal deletion mutations of muIL-1R revealed that the C-terminal boundary for receptor function is localized between 28 and 42 amino acids from the C-terminal end. The internal deletion mutants between amino acids 364 and 474 had a loss of activity, demonstrating the requirement for a large region of the mIL-1R cytoplasmic portion for receptor function. Amino acid substitution revealed that the putative nuclear localization elements (amino acids at 429-433, 523-527, and 507-519) and putative protein kinase C or A acceptor sites (Ser-431, Ser-509, Ser-528) do not participate in IL-1 signaling to induce IL-8 gene expression. A truncated mutation within the segment, which possesses homology with gp130, beta chain of IL-6R, or a point mutation of box 1- and box 2-like elements within the gp130 homologous segment, abolished the capacity to induce IL-8 gene expression, suggesting similar structural requirements in the cytoplasmic portion of several cytokine receptors. PMID- 8514785 TI - Assembly of in vitro synthesized large subunits into ribulose-bisphosphate carboxylase/oxygenase. Formation and discharge of an L8-like species. AB - Ribulose-bisphosphate carboxylase/oxygenase (Rubisco) from higher plants consists of eight approximately 53-kDa large subunits and eight approximately 14-kDa small subunits. Cytosolic ribosomes synthesize the small subunits as precursors, which enter the chloroplast, undergo proteolytic processing, and assemble with large subunits. Large subunits, synthesized in the chloroplast, first form a complex with the chloroplast chaperonin 60 (Cpn60(14)). In the presence of ATP, large subunits dissociate from Cpn60(14) and assemble into Rubisco. We now describe partial characterization of a new species, Z, containing radiotracer-labeled, newly synthesized pea Rubisco large subunits. Rubisco assembly occurs in low salt in the presence of small subunits and ATP. As with Rubisco assembly, the formation of Z is ATP-dependent and is inhibited by high chloride. Once formed, Z is stable except in high chloride. Z does not appear to interact directly with small subunits. However, after Z formation, Rubisco assembly occurs in an ATP independent reaction that requires KCl and small subunits. These results are consistent with the hypothesis that Z is a large subunit containing structure that can contribute large subunits to Rubisco under appropriate conditions. Z shares some physical characteristics with reported cyanobacterial L8 core particles. However, formation of Rubisco from Z in the absence of ATP and the presence of small subunits appears to require conditions that otherwise destabilize Z. PMID- 8514786 TI - The effects of varying the expression of a neutral cholesteryl ester hydrolase on the turnover of cholesteryl ester in rat hepatoma cells. AB - A neutral bile salt-dependent cholesteryl ester hydrolase (CEH) in rat liver has been shown to be indistinguishable from the pancreatic CEH by a number of criteria (Harrison, E. H. (1988) Biochim. Biophys. Acta 963, 28-34; Zolfaghari, R., Harrison, E. H., Ross, A. C., and Fisher, E. A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6913-6919; Camulli, E. D., Linke, M. J., Brockman, H. L., and Hui, D. Y. (1989) Biochim. Biophys. Acta 1005, 177-182). The rat hepatoma cell line Fu5AH, which lacks this particular CEH activity, was stably transfected with the cDNA of rat pancreatic CEH, and the effects on cholesterol and cholesteryl ester metabolism in clones with varying levels of CEH expression determined. In spite of significant amounts of intracellular enzyme protein demonstrated by Western blotting, in cell lysates there was a consistently low level of catalytic activity, and in cultured cells there was no evidence that CEH served as an effective intracellular cholesteryl ester hydrolase or synthase. In contrast, the catalytic activity of the secreted enzyme was relatively higher and there was a small, but significant, increase in the ability of high density lipoprotein (added to the medium) to promote the clearance of cholesteryl ester from cells secreting high levels of CEH. Overall, these results suggest that in the liver, intracellular CEH does not significantly affect the turnover of cholesteryl esters and warrant future studies focusing on the function of the secreted enzyme. For example, secreted CEH may modify lipoproteins and affect their interactions with cells. PMID- 8514787 TI - The extracellular hemoglobin of the earthworm, Lumbricus terrestris. Determination of subunit stoichiometry. AB - The giant extracellular hemoglobin of the earthworm, Lumbricus terrestris, has four major O2-binding chains, a, b, and c (forming a disulfide-linked trimer) and d ("monomer"). Participation of additional "linker" chains L1, L2, and L3 is necessary for the assembly of the approximately 3,900+ kDa two-tiered hexagonal structure. We have determined the proportions of linker chains, trimer, and chain d in the hemoglobin by reverse phase high performance liquid chromatography which resolves all of the components and also permits simultaneous determination of the heme content. The proportions of components were determined by two independent procedures: integration of the absorbance peaks at 220 nm and amino acid analysis of the peak fractions. The results indicate that the weight proportion of linker chains is 0.163 +/- 0.023. This value, together with molecular masses determined both by amino acid sequence analysis and by matrix-assisted laser desorption mass spectrometry, gives a molar ratio of abcd chains to linkers of 8:1, corresponding to the minimal unit (abcd)2.L. This ratio suggests that 24 (abcd)2 units and 24 linker chains form the complete structure with a total calculated mass of polypeptide of 3,975 kDa with hemes on chains a, b, c and d and on one linker. The calculated heme content is 3.1% not including carbohydrate. This accounts for a measured heme content of 3.0% on a polypeptide basis. Additional mass (approximately 133 kDa, 3.4%), attributed to carbohydrate, brings the total mass to 4,108 kDa with a minimum molecular mass/heme of 20,500 Da. The presence of equimolar quantities of three unique linker chains means that the apparent one twelfth structural units seen by electron microscopy cannot all be identical. PMID- 8514788 TI - Linker chain L1 of earthworm hemoglobin. Structure of gene and protein: homology with low density lipoprotein receptor. AB - The extracellular hemoglobins (Hbs) of annelids and tube worms are giant multisubunit proteins of up to approximately 200 polypeptides and molecular masses to at least 3,900 kDa. They differ from all other Hbs in having both O2 binding chains and "linker" chains. The latter are required for assembly and structural integrity of the protein and are deficient in or lack heme. We have determined the nucleotide sequences of the cDNA and gene for linker chain L1 of the hemoglobin of Lumbricus terrestris. The cDNA-derived amino acid sequence has 225 residues and a calculated molecular mass of 25,847 Da. The chain is 21-28% identical to linker chains of the related annelid Tylorrhynchus heterochaetus and the deep-sea tube worm Lamellibrachia sp. A remarkable feature of the linker chains is a conserved 38-39-residue segment that contains a repeating pattern of cysteinyl residues: (Cys-X6)3-Cys-X5-Cys-X10-Cys. This pattern, not present in any globin sequence, corresponds exactly to the cysteine-rich repeats of the ligand binding domains of the low density lipoprotein (LDL) receptors of man and Xenopus laevis. Furthermore, the cysteine-rich segment of linker chain L1 has the sequence Asp-Gly-Ser-Asp-Glu which is characteristic of LDL receptor repeats. Similar cysteine-rich sequences also occur in two other mammalian proteins, complement C9 and renal glycoprotein GP330. The results support the conclusion that the cysteine-rich motif of the LDL receptor and annelid Hbs is a multipurpose protein-binding unit of ancient origin which has been incorporated into diverse unrelated proteins, presumably by the process of exon shuffling. PMID- 8514789 TI - Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase. AB - A cDNA containing an open reading frame coding for the rat kidney cytochrome P 450 arachidonic acid epoxygenase was isolated from a male rat kidney cDNA library. Sequence analysis showed that with the exception of 11 nucleotides, this cDNA is identical with the published sequence for rat liver cytochrome 2C23 and encodes a polypeptide of 494 amino acids. Nucleic acid blot hybridization indicated that the levels of expression of the corresponding mRNA are high in rat kidney and liver and are undetectable in brain and heart. The cDNA coding region was cloned into a pCMV2 vector and expressed in COS-1 cells. The recombinant microsomal protein catalyzed the NADPH-dependent metabolism of arachidonic acid to a mixture of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids as the only oxygenation products. The enantiofacial selectivity of the recombinant protein was nearly identical with that reported for the kidney microsomal enzyme and generated 8(R),9(S)-, 11(R),12(S)-, and 14(S),15(R) with optical purities of 95, 85, and 75%, respectively. On the basis of mRNA abundance and the close similarities between the regio- and stereochemical selectivity of the recombinant and kidney microsomal proteins, we concluded that cytochrome P-450 2C23 is the predominant enzyme isoform responsible for arachidonic acid epoxidation in the rat kidney. PMID- 8514790 TI - Carboxyl-terminal portions of the alpha chains of fibrinogen and fibrin. Localization by electron microscopy and the effects of isolated alpha C fragments on polymerization. AB - The locations of the carboxyl-terminal two thirds of the A alpha chains, or the alpha C domains, were determined for fibrinogen and some of its derivatives by electron microscopy of rotary-shadowed preparations. A monoclonal antibody, G8, to the carboxyl-terminal 150 amino acids of the A alpha chain, binds near the central region of fibrinogen, indicating that the alpha C domains of most molecules are not normally visible because they are on or near the amino-terminal disulfide knot. At pH 3.5, fibrinogen and fibrin monomers appear to be similar, with a projection terminating in a small globular domain from each end of most molecules. In contrast, fragment X monomers, produced by cleavage of the alpha C domains from fibrinogen with plasmin, show no such projections. When fibrin monomer is brought to neutral pH under conditions where polymerization is delayed, individual molecules are still visible showing the alpha C domains as a single additional nodule near the central region. Moreover, analysis of clusters of molecules reveals some intermolecular associations via the alpha C domains. A 40-kDa fragment comprising the alpha C domain has been isolated from a plasmin digest of fibrinogen and characterized by SDS-polyacrylamide gel electrophoresis and determination of amino-terminal amino acid sequences. Electron microscopy of alpha C fragments reveals individual globular structures, as well as oligomeric aggregates. The addition of alpha C fragments to fibrin monomer followed by dilution to neutral pH to initiate polymerization results in lower turbidity, longer lag period, and slower maximum rate of turbidity increase. Also, electron microscopy reveals complexes of alpha C fragments with fibrin monomer at neutral pH. It appears that the free alpha C fragments can bind to the alpha C domains of fibrin, competing with the normal alpha C domain interactions involved in polymerization. PMID- 8514791 TI - Cloning and expression of a novel cyclic GMP-dependent protein kinase from mouse brain. AB - Synthetic oligonucleotides were used to amplify mouse brain cDNA sequences homologous to conserved regions of known cGMP-dependent protein kinases, and two classes of products were identified. The first class (CGKI) of amplification products contained approximately 1.0 kilobase (kb) of DNA sequence between the oligonucleotide primers, and this sequence showed a high degree of homology (90% identity) with the known bovine and human type I cDNA sequences for cGMP dependent protein kinase. The second class (CGKII) of amplification products contained approximately 1.1 kb of DNA sequence between the oligonucleotide primers, and this sequence showed a much lower homology (65% identity) with the bovine and human type I cDNA sequences. Northern blot analysis showed that CGKI transcripts of 8.5 kb were abundant in brain and lung, whereas a 7-kb transcript could be detected in testis. CGKII transcripts of 6 kb were also abundant in brain and lung but could be detected at lower levels in kidney. The CGKII amplification product was used to screen a mouse brain cDNA library, and four overlapping cDNA clones were isolated which comprised the entire CGKII coding region. The predicted CGKII protein consists of 761 amino acids and has a molecular mass of 87 kDa. The CGKII protein shows highest homology to the catalytic (66% amino acid identity) and regulatory domains (45% identity) of bovine and human CGKI. Little homology is observed at the amino terminus or in the region linking the regulatory and catalytic domains. An expression vector for mouse CGKII was constructed and transfected into COS-1 cells where it directed the expression of a protein kinase which was activated by cGMP with an apparent K alpha of 300 nM cGMP. PMID- 8514792 TI - Characterization of the human interleukin-2 receptor gamma chain gene. AB - The interleukin-2 (IL-2) receptor gamma chain is an essential component of high and intermediate affinity IL-2 receptors (IL-2Rs), playing critical roles for ligand binding and internalization. We report here the isolation and characterization of the genomic locus for human IL-2R gamma, which, like IL-2R beta, is a member of the cytokine receptor superfamily. The IL-2R gamma gene is composed of eight exons and seven introns and spans approximately 4.2 kilobases. Analogous to the IL-2R beta gene, the two pairs of conserved cysteines typical of cytokine receptor superfamily proteins are located in adjacent exons, and the conserved WSXWS motif is located in the exon preceding the one that encodes the transmembrane domain and a small part of the cytoplasmic domain. In each gene, the remainder of the cytoplasmic domain is encoded by the final two exons. Southern blot analysis suggests that IL-2R gamma is encoded by a single copy gene. Cross-hybridizing sequences were detected in DNA derived from a number of other mammalian species but not from yeast. Primer extension analysis and ribonuclease protection assays revealed that there are three principal transcription initiation sites located 32-38 nucleotides 5' to the translation initiation AUG codon. These sites are upstream of the 5' end of the published IL 2R gamma cDNA sequence. The region 5' to the transcription initiation sites exhibited promoter activity when cloned upstream of the luciferase reporter gene. With this study, the organization of the genes encoding all three chains (alpha, beta, and gamma) of the IL-2 receptor has been determined and promoters for each identified. PMID- 8514793 TI - In vivo sucrase-isomaltase and lactase-phlorizin hydrolase turnover in the fed adult rat. AB - We estimated in vivo turnover rates of sucrase-isomaltase and lactase-phlorizin hydrolase in adult rats. Fed animals received a primed continuous infusion of phenylalanine (300 microCi, 150 mumol Phe/100 g of body weight for 30 s, then 7.5 microCi, 3.75 mumol Phe/min for 10 to 140 min). Sucrase-isomaltase and lactase phlorizin hydrolase were immunoprecipitated from jejunal mucosal membranes; isoforms were separated by SDS-polyacrylamide gel electrophoresis. Endoglycosidase H digestions and (for lactase-phlorizin hydrolase) N-terminal amino acid sequencing were performed on all isoforms. Specific radioactivity of prosucrase-isomaltase and prolactase-phlorizin hydrolase isoforms reached isotopic equilibrium by 60 and 90 min, respectively. Specific radioactivity of brush border sucrase and lactase did not reach steady state. The isotope kinetic, N-terminal amino acid sequencing, and endoglycosidase H digestion data suggested that one of the high molecular weight lactase isoforms is a dimer of mature lactase. Compartmental modeling of specific radioactivity demonstrated that mean intracellular residence time is 59 min for prosucrase-isomaltase isoforms and 68 min for prolactase-phlorizin hydrolase isoforms. Mean residence time in the brush border was 5.8 h for sucrase and 7.8 h for lactase. Fractional synthesis rates were 414%/day for sucrase and 307%/day for lactase. Thus, in vivo brush border sucrase and lactase turn over at similar rates in the adult rat. PMID- 8514794 TI - Regulation of the alpha 1(I) collagen promoter via a transforming growth factor beta activation element. AB - A transforming growth factor-beta (TGF-beta) activating element (TAE), with a nuclear factor-1 (NF-1)-like sequence, was previously located 1.6 kilobases upstream from the transcription start site in the alpha 1(I) collagen promoter (Ritzenthaler, J. D., Goldstein, R. H., Fine, A., Lichtler, A., Rowe, D. W., and Smith, B. D. (1991) Biochem. J. 280, 157-162). Double-stranded TAE, but not NF-1 consensus sequences, abrogated TGF-beta stimulation of co-transfected collagen promoter-chloramphenicol acetyltransferase constructs. Mutations in non-NF-1 binding sites, located by methylation interference, eliminated activity of the TAE oligonucleotide. However, TAE sequences failed to bind in vitro expressed NF 1 protein, to compete for NF-1-binding proteins, and to bind with protein which reacts with antibodies to NF-1 family of proteins. Within the TAE there was an activator protein 2 (AP-2) binding site. Although AP-2 protein bound to TAE, antibodies to AP-2 did not react with nuclear protein-TAE complexes. TAE bound to a 34,000-Da protein on Southwestern analysis. However, the UV-cross-linked TAE nuclear protein complex was 82,000 Da. Finally, a dose-response study demonstrated that TGF-beta increased TAE nuclear binding proteins at lower doses with a different response curve than NF-1 nuclear binding proteins. Taken together these data demonstrated that TGF-beta functions in human lung fibroblasts to activate collagen transcription through TAE sites by protein complexes independent of NF-1 or AP-2 protein. PMID- 8514795 TI - Aberrant expression of high mobility group chromosomal protein 14 affects cellular differentiation. AB - High mobility group (HMG) 14 is a ubiquitous chromosomal protein that binds specifically to nucleosomal DNA and may be involved in a process that confers distinct properties to the chromatin structure of transcriptionally active genes. To explore the involvement of this protein in regulation of gene expression, we studied the effect of aberrant expression of HMG-14 protein on cellular differentiation. We produced stably transfected C2C12 mouse myoblasts expressing the human HMG-14 protein under the control of the mouse mammary tumor virus promoter. Transformed colonies retained their potential do differentiate into myotubes. Induction of human HMG-14 expression by dexamethasone inhibited the myogenic process. Revertant colonies, which lost the ability to express human HMG 14, regained the ability to differentiate into myotubes. Inhibition of myoblast differentiation by aberrantly expressed HMG-14 correlated with down-regulation of myogenic determination factors. The results suggest that proper cellular differentiation requires regulated expression of HMG-14 protein and are consistent with the possibility that this protein may be involved in gene regulation. PMID- 8514796 TI - Intermediates in degradation of the erythropoietin receptor accumulate and are degraded in lysosomes. AB - The erythropoietin receptor (EPO-R) is synthesized in transfected Ba/F3 cells as a major 64-kDa endoglycosidase H (Endo H)-sensitive species, with a single N linked oligosaccharide, and a minor 62-kDa unglycosylated form. Approximately half of the newly made EPO-R is processed to a mature 66-kDa form with a Golgi processed Endo H-resistant oligosaccharide, of which only a minor fraction is expressed at the cell surface. Both the Endo H-sensitive and the Endo H-resistant forms of the receptor have a half-life of 45-60 min (Yoshimura, A., D'Andrea, A. D., and Lodish, H. F. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 4139-4143). The mature, Endo H-resistant form of the EPO-R appears to be degraded in lysosomes or in other acidic organelles, since receptor degradation is blocked by treatment with NH4Cl, chloroquine, or leupeptin. A fraction of the Endo H-resistant EPO-R molecules is cleaved, generating two fragments of 46 and 39 kDa. The sizes of these fragments and their reactivities with carboxyl-terminal-specific antibodies indicate that the receptor is cleaved at two sites in the exoplasmic domain, 7 kDa apart, and carboxyl-terminal to the N-glycosylation site. Both fragments are membrane anchored and are probably formed in a late or post-Golgi compartment, since their formation is blocked by incubation of cells at 20 degrees C or by incubation with brefeldin A. These membrane-anchored COOH-terminal fragments are probably degraded in lysosomes or in other acidic vesicles as cell fractionation demonstrates that they colocalize with lysosomes, and similar to the intact EPO R, their degradation is inhibited by NH4Cl. Finally, double labeling immunofluorescence experiments demonstrate that in NH4Cl-treated cells both intact mature EPO-R and the 46- and 39-kDa fragments accumulate in lysosomes and presumably are normally degraded there. The sensitivity of the EPO-R to endoproteolytic cleavages in its exoplasmic domain may relate to its low surface expression and to its extreme metabolic instability. PMID- 8514797 TI - Phosphorylation and desensitization of human m2 muscarinic cholinergic receptors by two isoforms of the beta-adrenergic receptor kinase. AB - Studies of the human m2 (hm2) muscarinic cholinergic receptors (mAChR) have been performed to provide further insights into the potential regulation of these receptors by isoforms of the beta-adrenergic receptor kinase (beta ARK). The hm2 mAChR and the isoforms beta ARK1 and beta ARK2 were individually expressed in, and purified from, insect Sf9 cells infected with recombinant baculoviruses. The expressed hm2 receptors were tested as substrates for beta ARK1 and beta ARK2 in vitro using concentrations of receptors and kinases similar to those found in intact cells. The hm2 mAChR were phosphorylated in an agonist-dependent manner to 4-5 mol of phosphate/mol of receptor by beta ARK1 or beta ARK2. The reactions were highly dependent on agonist; the antagonist atropine, and heparin, a beta ARK inhibitor, both prevented the beta ARK-mediated phosphorylation. The rates of phosphorylation catalyzed by both isoforms were similar, with half-maximal phosphorylation occurring in less than 5 min. Under the conditions employed the stoichiometries, but not the rates, of phosphorylation catalyzed by both kinases were increased 2-3-fold by either the heterotrimeric G-protein G(o) or the beta gamma subunits of transducin. Phosphopeptide mapping experiments indicated that similar sites were phosphorylated by the two beta ARK isoforms. In order to test for functional effects of the phosphorylation mediated by the beta ARK isoforms, the receptors were reconstituted with purified G(o) and were tested for their ability to stimulate guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) binding. The conditions leading to maximal receptor phosphorylation resulted in a 30-50% reduction in the ability of the receptors to stimulate GTP gamma S binding to G(o). The results demonstrate that the hm2 mAChR are excellent substrates in vitro for both beta ARK1 and beta ARK2 and that extensive phosphorylation by these enzymes occurs in the presence of the beta gamma subunits of G proteins. The beta ARK-mediated phosphorylation of the m2 mAChR causes a perturbation of receptor/G-protein coupling. PMID- 8514798 TI - The Drosophila kinesin light chain. Primary structure and interaction with kinesin heavy chain. AB - Kinesin light chain (KLC) complexes with the kinesin heavy chain (KHC) to form native kinesin. Proposed functions of KLC include coupling of cargo to KHC or modulation of KHC ATPase activity. In this paper we use the KHC tail, which binds specifically to KLC in blot overlays, as a probe to clone a cDNA encoding KLC from a Drosophila expression library. The identified clone encodes a protein with 70% amino acid identity to rat KLC. Drosophila KLC is predicted to form an alpha helical coiled-coil between residues 34 and 129, followed by five imperfect tandem repeats of unknown function and a sixth shorter motif. These repeats are highly conserved across species. The Drosophila KLC gene is located at 69D on the third chromosome and is widely expressed, with 1.8-kb transcripts in most tissues, and slightly smaller transcripts in gonads. Finally, we present evidence that the heptad repeats of KLC are required for interaction with the KHC tail. Since the KHC tail used in our assay includes about 20 heptad repeats, this result suggests that KHC and KLC interact via coiled-coils. Such an interaction could provide stability to the KHC-KLC complex in vivo. PMID- 8514799 TI - Construction, characterization, and selected site-specific mutagenesis of an anti single-stranded DNA single-chain autoantibody. AB - Single-chain antibodies are comprised of immunoglobulin light and heavy chain variable domains joined through a polypeptide linker. A single-chain autoantibody, containing the 14-amino acid 212-polypeptide linker (GSTSGSGKSSEGKG), was constructed based on the light and heavy chain variable region gene sequences of anti-single-stranded DNA autoantibody BV04-01 (IgG2b, kappa). Following protein expression in Escherichia coli, denaturation, refolding, and affinity purification, single-chain autoantibody 04-01 binding with single-stranded DNA and poly(dT) was characterized in solid-phase and solution-phase assays. Homopolymer ligand binding results demonstrated that single-chain autoantibody 04-01 possessed anti-DNA binding properties similar to BV04-01 IgG and Fab fragments. Based on x-ray crystallographic analyses of BV04 01, site-specific mutagenesis studies were conducted on 2 residues (L32Tyr and H100aTrp) involved in aromatic stacking interactions with the middle thymidine of a (dT)3 ligand. PMID- 8514800 TI - The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins. AB - The amino acid sequence of the rat liver mitochondrial tricarboxylate transport protein has been deduced from its corresponding cDNA. Using the polymerase chain reaction, with primers derived from amino acid sequence information that we obtained by direct sequencing of the purified transporter and its internal peptides, a cDNA fragment was amplified that encodes approximately two-thirds of the tricarboxylate transport protein. This cDNA fragment was used to screen a rat liver lambda gt11 cDNA library which permitted the isolation and sequencing of a cDNA clone that encodes the entire tricarboxylate transporter. The clone is 1927 base pairs in length with 5'- and 3'-untranslated regions of 419 and 572 base pairs, respectively. The open reading frame encodes a mature transport protein of 298 amino acids preceded by a presequence of 13 residues. Analysis of the tricarboxylate transporter sequence indicates that it contains three related sequence domains, each of approximately 100 amino acid residues in length. Dot plot comparisons and sequence alignment indicate that these domains are related to each other, as well as to domains of similar length that are present in other mitochondrial transporters. Hydrophobicity analysis predicts that the tricarboxylate carrier contains six membrane-spanning alpha-helices (two per 100 amino acid sequence domain) and has permitted the construction of an initial model for the topography of this transporter within the mitochondrial inner membrane. Finally, Southern blot analysis of both rat and human genomic DNA demonstrates the presence of multiple sequences related to the tricarboxylate transporter in both genomes. These studies provide the first information on the primary structure of the mitochondrial tricarboxylate transport protein. We are now able, on the basis of both structural and functional considerations, to assign this metabolically important transporter to the mitochondrial carrier family, the members of which are likely to have evolved from a common genetic origin. PMID- 8514801 TI - Coordinate expression of the alpha and beta chains of human granulocyte macrophage colony-stimulating factor receptor confers ligand-induced morphological transformation in mouse fibroblasts. AB - Two distinct components, alpha and beta chains, which compose the high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) do not contain any catalytic domains of known enzymes. However, in mouse lymphoid cell lines transfected with cDNAs of the both chains, GM-CSF triggers tyrosine phosphorylation of several cellular proteins and allows continuous proliferation. To elucidate whether the high affinity receptor functions in nonhematopoietic cells, we have reconstituted human GM-CSF receptor in mouse NIH3T3 fibroblasts. In NIH3T3 clones, in which the high affinity receptor is reconstituted, human GM CSF has triggered rapid tyrosine phosphorylation of cellular proteins, transfected beta chain, and another protein of 40-45 kDa. Moreover, human GM-CSF stimulated DNA synthesis and induced morphological transformation. These observations indicate that coordinately expressed alpha and beta chains of human GM-CSF receptor activates intrinsic protein-tyrosine kinases by the stimulation with human GM-CSF and that the activated protein-tyrosine kinases phosphorylate tyrosine residues of an intrinsic 40-45-kDa protein and the transfected beta chain in NIH3T3 cells. Activation of the protein-tyrosine kinases is likely to have biological functions to induce DNA synthesis and morphological transformation of mouse fibroblasts. PMID- 8514802 TI - Complex formation between proteins encoded by the ski gene family. AB - The c-ski proto-oncogene product (c-Ski) is localized in the nuclei, but its function and biochemical properties are unclear. C-Ski can bind to DNA only in association with uncharacterized protein(s). A lambda gt11 cDNA library was screened with the biotinylated Ski to isolate genes encoding proteins capable of forming complexes with Ski. Two clones encoding Ski itself or the ski-related gene product SnoN were isolated in this manner, suggesting that Ski can form a complex with Ski itself or with SnoN. Trimerization of Ski with itself and SnoN was also confirmed by protein cross-linking and protein blot analysis. The carboxyl-terminal 1/5 regions of Ski and SnoN are required for complex formation. This region has a homology between two proteins and two putative leucine zipper like structures, suggesting that these leucine zipper-like structures mediate trimerization by making side-to-side interactions between the conserved leucines. Thus, Ski and SnoN have the capacity to associate with other proteins, and a complex formation of c-Ski with itself, SnoN, and uncharacterized proteins might play a key role in the function of Ski. PMID- 8514803 TI - Sensitivity of Escherichia coli succinyl-CoA mutants at Trp beta 76 to clostripain and to trypsin. ADP and ATP protect against cleavage by clostripain at Arg beta 80. AB - Mutant forms of Escherichia coli succinyl-CoA synthetase, W76F (Trp beta 76 replaced by Phe) (Nishimura, J. S., Mann, C. J., Ybarra, J., Mitchell, T., and Horowitz, P. M. (1990) Biochemistry 29, 862-865), and W43,76,248F (all three Trp replaced by Phe) were found to be more sensitive to proteolysis by clostripain than the wild-type enzyme or other Trp mutant proteins. Like wild-type enzyme, sensitivity to trypsin was apparent when the enzyme forms were in the dephosphorylated state. Sensitivity to clostripain was the same, whether mutant or wild-type forms were in the phosphorylated or dephosphorylated state. The substrates ADP and ATP both protected the enzymes against inactivation by clostripain, with dissociation constants for protection of W76F of 33 and 125 microM, respectively. Polyacrylamide gel electrophoresis of clostripain digests revealed preferential digestion of the beta-subunit and the appearance of 40- and 31-kDa species, with amino termini corresponding to residues 15 and 81, respectively, of the beta-subunit. Mutagenic replacement of Arg beta 80, but not Arg beta 14, with Lys resulted in an enzyme that was as resistant to clostripain as wild-type enzyme. These results suggest that Arg beta 80 is the principal site of inactivation by clostripain and may be involved in the binding of ADP and ATP to succinyl-CoA synthetase. PMID- 8514804 TI - Stage-specific glycosphingolipids from amastigote forms of Leishmania (L.) amazonensis. Immunogenicity and role in parasite binding and invasion of macrophages. AB - Neutral glycosphingolipids (GSLs) from amastigote forms of Leishmania (L.) amazonensis were isolated, and their structures and biological properties were characterized. Based on various immunochemical methods, these GSLs were shown to be expressed at certain stages of amastigote development. GSLs were extracted and purified from amastigotes of hamster foot lesions by established procedures. Three mouse monoclonal antibodies (MoAbs) specific for carbohydrate epitopes of these GSLs were established, and their inhibition of parasite binding and macrophage invasion was analyzed. MoAb ST-3 inhibited 80% of macrophage invasion by amastigotes and 60% of that by promastigotes. Since GSLs reacting with MoAb ST 3 were found in amastigotes but not in promastigotes, ST-3 reactivity with promastigotes presumably depends on an epitope present on an unidentified promastigote glycoconjugate. MoAbs ST-4 and ST-5 inhibited 60-80% of macrophage invasion by amastigotes but were not effective in preventing macrophage invasion by promastigotes. Fab fragments of ST-3 inhibited invasion of cultured mouse macrophages by amastigotes (80%) or promastigotes (60%). The GSL with the simplest structure recognized by these MoAbs was isolated and characterized (by negative ion fast atom bombardment-mass spectrometry, gas chromatography-mass spectrometry of the permethylated compound, degradation with exoglycosidases, and 1H NMR) as the novel globoseries structure Gal beta 1-->3Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->Cer, which has beta 1-->3Gal in place of the beta 1-->3GalNAc of globoside. The ceramide contains a 16:0 fatty acid and d18:1 sphingosine as the long chain base. The MoAbs also reacted with a series of GSLs from amastigote forms of L. amazonensis, with longer carbohydrate chains, probably containing identical end groups Gal beta 1-->3Gal alpha 1-->R. Expression of surface GSLs may render amastigote forms more effective than promastigotes in binding and invading host macrophages, thus enhancing the infectious process. PMID- 8514805 TI - Purification and properties of LR1, an inducible DNA binding protein from mammalian B lymphocytes. AB - LR1 is a lipopolysaccharide-inducible B cell-specific DNA binding activity, with sites in the immunoglobulin heavy chain enhancer and switch regions. We describe the purification of this 106-kDa protein from nuclear extracts of PD31 murine pre B cells, using three chromatographic steps. The DNA binding activity of LR1 is dependent upon phosphorylation, and we show that LR1 is post-translationally modified by N-acetylglucosamine addition. The importance of regulatory modification to LR1 DNA binding activity is apparent from the chromatographic pattern on the anion exchange resin Mono Q: while the LR1 polypeptide elutes over a broad salt range from the column, DNA binding activity is confined to a narrow peak eluting at the highest salt. PMID- 8514806 TI - Novel use of an iodo-myristyl-CoA analog identifies a semialdehyde dehydrogenase in bovine liver. AB - We describe here the identification, purification, and characterization of a semialdehyde dehydrogenase with a novel fatty acid binding function. The coenzyme A derivative of an 125I-labeled long chain saturated fatty acid (13-iodo tridecanoate) was used to tag proteins which bind myristoyl-CoA. A prominent 57 kDa band was identified, which was isolated from bovine liver by a high salt extraction followed by ammonium sulfate precipitation. Sequential chromatographic separation using phenyl-Sepharose, hydroxyapatite, DEAE-Sepharose, Mono Q, and Fast Flow S resins resulted in a purified protein that migrated as a single band of 57 kDa on denaturing gels. Sephacryl-200 gel filtration provided a native molecular mass estimation of 118 kDa suggesting that this protein exists as a dimer. Two-dimensional gel analysis resolved three isoform variants with pI values of 7.4, 7.7, and 7.9, respectively, and established that the pI = 7.9 form has the highest propensity for fatty acid binding. We proceeded to generate tryptic peptides from the purified protein and subjected several peptides to microchemical sequencing. Degenerate oligonucleotide probes were designed and polymerase chain reaction was used to generate a unique nucleotide sequence. Subsequent screening of a bovine liver cDNA library yielded a 1.7-kilobase clone which encodes a protein of 537 amino acids (58 kDa) with 95% identity to mammalian methylmalonate semialdehyde dehydrogenase (MMSDH). In vitro assays confirmed that the purified 57-kDa protein exhibited MMSDH activity, and that preincubation of the enzyme with fatty acyl-CoA inhibited its dehydrogenase activity. The myristyl-CoA analog therefore serves as an affinity label for MMSDH. We propose that fatty acyl CoAs may have the potential to function as enzyme regulators in vivo. PMID- 8514807 TI - A difference in the rate of ribosomal elongation balances the synthesis of eukaryotic translation initiation factor (eIF)-2 alpha and eIF-2 beta. AB - Eukaryotic translation initiation factor 2 (eIF-2) is a heterotrimer composed of three subunits designated alpha, beta, and gamma. These proteins exist in equimolar amounts in the cell and have not been detected as isolated subunits. Our research examines the basis of their balanced synthesis. Northern analysis of K562 cell mRNA revealed that eIF-2 beta was five times more abundant than eIF-2 alpha. However, immunoprecipitation of pulse-labeled K562 cells showed an equimolar rate of synthesis of eIF-2 alpha and -beta despite the 5-fold difference in the size of their mRNA pools. Addition of equal amounts of synthetic capped mRNA for eIF-2 alpha and eIF-2 beta to an in vitro translation reaction produced five times more eIF-2 alpha protein than eIF-2 beta. Determination of the polysome profile for alpha and beta mRNA in K562 cells indicated eIF-2 alpha was translated more efficiently than eIF-2 beta. Substitution of either the initiation codon context or the leader of the beta mRNA for that of alpha had only a minor effect on the translational efficiency of beta. Comparison of the rate of ribosomal elongation for the two mRNAs indicated that ribosomes associated with the beta mRNA elongate at a rate 4-fold less than that of eIF-2 alpha. Thus, the balanced translation of alpha and beta mRNA is primarily the result of a 4-fold difference in the rate of ribosomal elongation. PMID- 8514808 TI - Hand position affects elbow joint load during push-up exercise. AB - Electromagnetic motion sensors and a piezoelectric force plate were used to record simultaneously upper-extremity motion and forces in nine healthy male subjects during push-ups in six different hand positions. The intersegmental loading pattern on the elbow joint during a push-up exercise was investigated. The importance of hand position on these loads was examined. Peak forces exerted on the elbow joint along the forearm axis averaged 45% of the body weight for the 'normal' hand position and were significantly decreased if hands were positioned either 'apart' or 'superior' from 'normal'. The peak torque in the 'normal' position tended to produce elbow flexion and was 2305.9 N cm, or 56% of the maximal isometric extensor torque, which was significantly different from hands 'apart' and hand 'together' at 29 and 71% of the maximal isometric torque, respectively. The maximum torque about the forearm axis tended to produce forearm pronation with a mean value of 315.4 N cm (35% of the maximal isometric supinator torque). The maximum valgus torque at the elbow opposed by the medial ligamentous structure was 1241 N cm and was significantly increased if the hand was positioned superiorly. The valgus torque increased by 42% for the one-handed push up under simulated fall condition. The results of this analysis give an insight into the biomechanics of a normal elbow and to its load-carrying capacity. The data may be extrapolated to the design of rehabilitation programs and possibly to the mechanisms of forearm injury during a fall. PMID- 8514809 TI - Control of whole body balance in the frontal plane during human walking. AB - A whole-body inverted pendulum model was used to investigate the control of balance and posture in the frontal plane during human walking. The model assessed the effects of net joint moments, joint accelerations and gravitational forces acting about the supporting foot and hip. Three video cameras and two force platforms were used to collect kinematic and kinetic data from repeat trials on four subjects during natural walking. An inverse solution was used to calculate net joint moments and powers. Whole body balance was ensured by the centre of mass (CM) passing medial to the supporting foot, thus creating a continual state of dynamic imbalance towards the centerline of the plane of progression. The medial acceleration of the CM was primarily generated by a gravitational moment about the supporting foot, whose magnitude was established at initial contact by the lateral placement of the new supporting foot relative to the horizontal location of the CM. Balance of the trunk and swing leg about the supporting hip was maintained by an active hip abduction moment, which recognized the contribution of the passive accelerational moment, and countered a large destabilizing gravitational moment. Posture of the upper trunk was regulated by the spinal lateral flexors. Interactions between the supporting foot and hip musculature to permit variability in strategies used to maintain balance were identified. Possible control strategies and muscle activation synergies are discussed. PMID- 8514810 TI - Assessment of gait patterns using neural networks. AB - A new approach for the assessment of gait patterns is presented. The use of neural network techniques for decision making in gait analysis is for some purposes more effective than biomechanical methods or conventional statistics. To demonstrate this, a neural network was trained to distinguish 'healthy' from 'pathological' gait. The algorithm presented here can be used for several purposes because it learns from examples of diagnosed gait patterns without having any built-in model of gait. PMID- 8514811 TI - A nonlinear fluid model for pulmonary blood circulation. AB - In this paper, we apply a quasi-one-dimensional unsteady nonlinear fluid model to study human pulmonary circulation. Eighteen generations of blood vessels composed of the branching arterial, capillary and venous distensible vessel segments make up the complete pulmonary circulation. The numerical result gives satisfactory agreement with the physiological experimental data: a dramatic pressure drop occurs in the arterioles and postcapillaries, a negative transmural pressure is shown in the postcapillary and small venous segments, a large reverse flow occurs in the main pulmonary artery during the diastolic period, and the reverse flow decreases gradually along the pulmonary tree. In the microgravity case where g = 180 cm s-2, the computation illustrated the effect of gravity force on the blood distribution in the different parts of the pulmonary circulation. The effect of gravity on the total output is not obvious. The effect of local factors which initiate the variations of the geometrical or pulmonary circulation can be stimulated quantitatively by this model. The proposal model can be very useful for clinical practice and for studying the extreme cases which are very difficult to investigate by experiments. PMID- 8514812 TI - Measurement of strain and analysis of stress in resting rat left ventricular myocardium. AB - A technique has been developed for measuring two-dimensional strains in the left ventricle of the isolated arrested rat heart subjected to passive ventricular loading. The pressure-volume relationship was found in eight hearts during inflation of a left ventricular balloon. With the zero-pressure state as reference, in-plane strain components were determined using a triangle of ultrasonic dimension transducers (0.6-0.8 mm diameter) placed 3-6 mm apart in the midwall of the left ventricle. Mean circumferential (fiber) strain was larger than longitudinal (cross-fiber) strain (0.108 +/- 0.045, 0.055 +/- 0.045, respectively, at 11 mmHg), and shear strain (-0.048 +/- 0.029) was negative, consistent with left-handed torsion. The in-plane angle of greatest stretch was uniform with inflation (range = -26.5 degrees to -34.5 degrees). The equatorial region of the left ventricle was modeled with finite element analysis of a transversely isotropic thick-walled cylindrical shell subjected to internal loading and axial forces. The material parameters of an exponential strain energy function were optimized so that the least-squares difference between the predicted and the measured midwall strains was minimized. Material properties, stress and strain in the rat heart were compared to values predicted for the dog. In both species the tissue was stiffer in the fiber direction than in the cross fiber direction. The ratio of fiber to cross-fiber stiffness was lower in the rat (2.50) than in the dog (5.24) at low loads and approximately equal at higher loads (1.63 and 1.39, respectively). The computational and experimental analyses showed that the larger shear strain and more nonuniform in-plane extension in the rat may be an indication of significantly different anisotropic material properties in these two species, and implies differences in the collagen ultrastructure. PMID- 8514813 TI - The relation between resonant frequencies and torsional stiffness of long bones in vitro. Validation of a simple beam model. AB - The results of vibration analysis experiments and impact torsion tests performed on excised animal long bones were used to validate a simple beam model for the prediction of torsional stiffness from resonant frequencies. Resonant frequency data on two mutually perpendicular bending vibration modes of 142 excised long bones were evaluated. Torsional stiffness of the same bones had been determined by an impact torsion test. Using a simple beam model, a theoretical relation between resonant frequencies and torsional stiffness was derived. If total bone mass and bone length are known, the formula thus derived allows one to calculate torsional stiffness from resonant frequencies. Linear regression analysis shows a strong correlation between the measured and the calculated torsional stiffness for sheep femora (r2 = 0.63, n = 24), dog femora (r2 = 0.94, n = 34), dog tibiae (r2 = 0.79, n = 18) and monkey radii (r2 = 0.77, n = 66). It was found that this linear relation was valid not within one bone type alone. Linear regression analysis on the combined data of all bones demonstrated that all bones obeyed the same global linear relation between measured and the calculated torsional stiffness (r2 = 0.98, n = 142). This implies that one and the same beam model is valid for the different bone types investigated. The calculation of stiffness from resonant frequencies, however, requires total bone mass, m, and length to be known. In view of in vivo applications, the feasibility of using total bone mineral content (TBMC) as a measure for m was investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514814 TI - Experimental investigation of unsteady flow behaviour within a sac-type ventricular assist device (VAD). AB - The flow behaviour of human blood in a pneumatically driven sac-type ventricular assist device (VAD) has been simulated by a non-Newtonian polymer (Separan) solution, and investigated by both a one-component laser Doppler anemometer (LDA) in back-scattering mode and flow visualisation. The device was driven by a pneumatic driver with a squarewave output pressure, and was operated at a pumping rate of 70 bpm, and a systolic duration of 35% of the pumping cycle. The preload and the average afterload to the device were set at 10 mmHg and 100 mmHg, respectively. The output flowrate was 4.05 l min-1. The wall of the peripheral and the central parts of the blood chamber of the VAD were well 'washed' by a main vortex developed during filling and the flow components perpendicular to the base of the VAD produced by the diaphragm motions, respectively. Flow recirculation regions were found at several locations. Around the junction between the tube sections and the blood chamber, the recirculation with an associated fluid particle deposition indicates an underlying risk of thrombus formation. This risk will be reduced by modifying the device design. The maximum turbulent shear stress estimated from the maximum turbulent normal stress (74 N m 2), is unlikely to cause significant damage to blood for the exposure times found. The maximum particle residence time was found to be closely related to the heart rate and the degree of completion of ejection/filling. At a given flow rate, the operating conditions which produce the highest stroke volume give the shortest residence times. PMID- 8514815 TI - Transport of fluid and ions through a porous-permeable charged-hydrated tissue, and streaming potential data on normal bovine articular cartilage. AB - Using the triphasic mechano-electrochemical theory [Lai et al., J. biomech. Engng 113, 245-258 (1991)], we analyzed the transport of water and ions through a finite-thickness layer of charged, hydrated soft tissue (e.g. articular cartilage) in a one-dimensional steady permeation experiment. For this problem, we obtained numerically the concentrations of the ions, the strain field and the fluid and ion velocities inside when the specimen is subject to an applied mechanical pressure and/or osmotic pressure across the layer. The relationships giving the dependence of streaming potential and permeability on the negative fixed charge density (FCD) of the tissue were derived analytically for the linear case, and calculated for the nonlinear case. Among the results obtained were: (1) at a fluid pressure difference of 0.1 MPa across the specimen layer, there is a 10% flow-induced compaction at the downstream boundary; (2) the flow-induced compaction causes the FCD to increase and the neutral salt concentration to decrease in the downstream direction; (3) while both ions move downstream, relative to the solvent (water), the anions (Cl-) move with the flow whereas cations (Na+) move against the flow. The difference in ion velocities depends on the FCD, and this difference attained a maximum at a physiological FCD of around 0.2 meq ml-1; (4) the apparent permeability decreases nonlinearly with FCD, and the apparent stiffness of the tissue increases with FCD; and (5) the streaming potential is not a monotonic function of the FCD but rather it has a maximum value within the physiological range of FCD for articular cartilage. Finally, experimental data on streaming potential were obtained from bovine femoral cartilage. These data support the triphasic theoretical prediction of non monotonicity of streaming potential as a function of the FCD. PMID- 8514816 TI - Frictional interface micromotions and anisotropic stress distribution in a femoral total hip component. AB - A numerical model of a femoral total hip component based on the finite element method is developed to evaluate the relative micromotions at the bone-implant interface and the stress distribution in the femoral bone. The interface is modelled as unilateral contact involving Coulomb's dry friction between the bone and the implant. In addition, the model includes inhomogeneity, anisotropy as well as plasticity of both cortical and spongious bones. An automatic data processor coupled to a three-dimensional mesh generator is designed to extract cortical bone geometry and inhomogeneous distribution of trabecular bone density from data obtained with quantitative computed tomography (QCT). A preliminary application is conducted to evaluate the mechanical behaviour of an existing bone prosthesis structure for two typical loadings: a load simulating the single leg stance and a load simulating the stair climbing stance. The obtained results are subdivided in two parts. Firstly, the characterization of stress transfer and micromotions at the bone-stem interface. The peak value of the shear micromotions reaches 600 microns in the proximal medial region with a friction coefficient equal to 0.6. An analysis of the influence of the friction coefficient reveals that the shear and distractive micromotions as well as the shear and normal stresses depend strongly on this coefficient. Secondly, the representation of stresses in the femoral bone. Determination of complementary invariants such as the hydrostatic pressure, the deviatoric stress and anisotropic stresses brings additional insights in the evaluation of the stress field in the femoral bone. PMID- 8514817 TI - A panning DLT procedure for three-dimensional videography. AB - The direct linear transformation (DLT) method [Abdel-Aziz and Karara, APS Symposium on Photogrammetry. American Society of Photogrammetry, Falls Church, VA (1971)] is widely used in biomechanics to obtain three-dimensional space coordinates from film and video records. This method has some major shortcomings when used to analyze events which take place over large areas. To overcome these shortcomings, a three-dimensional data collection method based on the DLT method, and making use of panning cameras, was developed. Several small single control volumes were combined to construct a large total control volume. For each single control volume, a regression equation (calibration equation) is developed to express each of the 11 DLT parameters as a function of camera orientation, so that the DLT parameters can then be estimated from arbitrary camera orientations. Once the DLT parameters are known for at least two cameras, and the associated two-dimensional film or video coordinates of the event are obtained, the desired three-dimensional space coordinates can be computed. In a laboratory test, five single control volumes (in a total control volume of 24.40 x 2.44 x 2.44 m3) were used to test the effect of the position of the single control volume on the accuracy of the computed three dimensional space coordinates. Linear and quadratic calibration equations were used to test the effect of the order of the equation on the accuracy of the computed three dimensional space coordinates. For four of the five single control volumes tested, the mean resultant errors associated with the use of the linear calibration equation were significantly larger than those associated with the use of the quadratic calibration equation. The position of the single control volume had no significant effect on the mean resultant errors in computed three dimensional coordinates when the quadratic calibration equation was used. Under the same data collection conditions, the mean resultant errors in the computed three dimensional coordinates associated with the panning and stationary DLT methods were 17 and 22 mm, respectively. The major advantages of the panning DLT method lie in the large image sizes obtained and in the ease with which the data can be collected. The method also has potential for use in a wide variety of contexts. The major shortcoming of the method is the large amount of digitizing necessary to calibrate the total control volume. Adaptations of the method to reduce the amount of digitizing required are being explored. PMID- 8514818 TI - A procedure to validate three-dimensional motion assessment systems. AB - The automation provided by computer-assisted motion-tracking systems allows for three-dimensional motion and force analysis. These systems combined with mathematical modelling are able to analyse quickly the intricate dynamics of human movement. Understanding the limitations of human motion analysis as performed by the present measurement techniques is essential for proper application of the results. It is necessary to validate the analysis system prior to subject testing. This paper provides a validation of an optoelectric motion tracking system used in a dynamic knee assessment study. While the validation is shown with one particular system only, it is suggested that all systems used in two- or three-dimensional motion analysis should be tested similarly in the actual configuration used. Three simple mechanical representations of the human knee have been used in this validation. The first model provided an understanding of the source and behaviour of the error introduced to the accuracy of defining a vector between the recorded coordinates of two markers. The other two models investigated the effect of processing methods specific to the knee analysis project. Separating the markers by at least 180 mm is recommended to produce stable vectors. Relative joint angles could be calculated in all three planes of rotation. The error in calculating flexion and longitudinal rotation was less than 2.0 degrees, while calculating adduction introduced errors of 4.0 degrees. Force calculations were found to be within 8%. The system behaviour was found to be consistent within the calibrated volume about the force platform. Simple mechanical models combined with straightforward procedures can provide validation in terms of clinically relevant parameters. PMID- 8514819 TI - On hydraulic strengthening of bones. PMID- 8514820 TI - The relative importance of extracellular and intracellular calcium in the responses of the human vas deferens to noradrenaline and potassium: a study using Ca(2+)-deprivation and Ca(2+)-antagonists. AB - 1. Mechanical responses of the human vas deferens, activated by noradrenaline (50 100 microM) or high potassium (130 mM), showed either biphasic shortening or lengthening or a combination of initial shortening and lengthening. These are interpreted as representing the contractions of longitudinal and circular muscle respectively. 2. Caffeine (10-20 mM) induced only shortening responses which were 86% (SE 34, n = 7) of that caused by noradrenaline (100 microM). 3. The calcium channel antagonists, nifedipine, verapamil and diltiazem (0.01-10 microM), inhibited responses to high potassium, and the initial phase of shortening and lengthening responses to noradrenaline. However, the secondary phase of the shortening response to noradrenaline (100 microM) was relatively insensitive to these antagonists. 4. In calcium-free (1 mM EGTA) media, noradrenaline (100 microM) could repeatedly induce both shortening and lengthening tonic responses which were 39 +/- 13% (n = 4) and 40 +/- 16% (n = 5) of their values in Krebs media. Except for a small shortening, responses to high potassium were abolished. Calcium-free media also blocked phasic bursts of mechanical activity. 5. Calcium removal during a prolonged exposure to noradrenaline (50 microM) caused a fall of tension of the lengthening but not the shortening response. Depletion of intracellular stores caused an inhibition of the responses to noradrenaline. Recovery of responses following restoration of calcium was blocked by nifedipine for the shortening response but not for lengthening. 6. We conclude that longitudinal and circular muscle rely to different degrees on activation by extracellular calcium and intracellular mechanisms. The longitudinal, but not circular, muscle appears mainly to use an intracellular calcium pool which is replenished via nifedipine-sensitive calcium channels and has a caffeine sensitive store. Evidence suggesting differences in the role of calcium and processes controlling its entry during activation of both muscle types is presented and discussed. PMID- 8514821 TI - Effects of vasoactive intestinal polypeptide (VIP) on the neuromuscular complex in the bovine ovarian follicle wall. AB - 1. When stimulating the local nerves in the bovine ovarian follicle wall preparation (4 Hz, 1 ms pulse duration and 7.5 V between the electrodes) vasoactive intestinal polypeptide reduced the neurogenic contraction and at the highest concentration tested (3 x 10(-7) M) almost abolished the response. Peptide histidine isoleucine only slightly reduced the contraction. 2. Strips from the follicle wall of bovine ovaries were incubated in Krebs-Ringer solution containing [3H]-noradrenaline for measurement of transmitter liberation during electrical field stimulation (5 Hz frequency, 1 ms pulse duration, 10 V between the electrodes). Vasoactive intestinal polypeptide had no effect on the electrically induced efflux of radioactivity. 3. Vasoactive intestinal polypeptide and its related peptide, peptide histidine isoleucine, relaxed precontracted follicle strips dose dependently with I(max) at 3 x 10(-7) M of 60% and 40% respectively. 4. Vasoactive intestinal polypeptide 10(-7) M did not alter the EC50 value of the noradrenaline-(10(-9)-10(-4) M) or carbachol-induced (10( 8)-3 x 10(-4) M) contraction in the follicle strips, but significantly reduced the E(max) value of the noradrenaline but not the carbochol-mediated contraction. 5. These results suggests that vasoactive intestinal polypeptide, and to some extent peptide histidine isoleucine, have a postjunctional role in ovarian follicle contractility and might further interfere with the ovulatory process. PMID- 8514822 TI - Dual action of ranitidine at cholinergic sites in the rat isolated anococcygeus muscle. AB - 1. The effects of ranitidine on contractile responses of the rat isolated anococcygeus muscle to acetylcholine (ACh) and carbachol (CCh) were investigated. 2. Four consecutive cumulative concentration-response curves (CRCs) for ACh or CCh were constructed in the absence or presence of ranitidine. The mean EC50 values were determined from the individual CRCs and used for the calculation of the corresponding EC50 ratios. 3. Ranitidine (0.01, 0.05 and 0.5 mM) produced a progressively leftward shift of the ACh curves; the corresponding EC50 ratios obtained were 3.2 +/- 0.4, 5.7 +/- 0.5 and 9.4 +/- 1.4. Neostigmine 0.5 microM alone or in combination with ranitidine 0.1 mM produced very marked leftward shifts of the ACh curves (EC50 ratios 68.2 +/- 14.3 and 56.3 +/- 9.6 respectively). In contrast, ranitidine (0.05, 0.5 and 2 mM) produced a rightward and parallel shift of the CCh curves (EC50 ratios 1.0 +/- 0.1, 3.4 +/- 0.32 and 12.5 +/- 1.7 respectively). 4. Ranitidine can therefore mediate a dual action at cholinergic sites in the rat isolated anococcygeus muscle, actions which can be attributed to its inherent anticholinesterase and antimuscarinic activity. The relatively marked anticholinesterase action of ranitidine was rather surprising in view of the limited cholinergic innervation present in the rat anococcygeus muscle. PMID- 8514823 TI - The influence of L-NG-nitro-arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle. AB - 1. The possibility of an interaction between the motor sympathetic and inhibitory non-adrenergic, non-cholinergic (NANC) nerves in the rat anococcygeus was investigated using L-NG-nitro-arginine (L-NOARG), an inhibitor of L-arginine: NO synthase. 2. L-NOARG (50 microM) increased contractions induced by field stimulation (20 s trains; 0.5-40 Hz); overall, the frequency-response curve was displaced six-fold to the left. D-NOARG (50 microM) was without effect. 3. The potentiation produced by L-NOARG was reversed by 200 microM L-, but not D-, arginine. 4. L-NOARG had no effect on contractions induced by exogenous noradrenaline (NA) or on field stimulation-induced overflow of tritium from muscles previously loaded with [3H]-NA. 5. It is concluded that the endogenous nitrate NANC transmitter does not influence release of NA from the sympathetic nerves and the potentiation of contractions induced by field stimulation in the presence of L-NOARG most probably results from removal of the opposing relaxing influence of concomitantly released NANC transmitter. PMID- 8514824 TI - On the site of action and inactivation of adenosine by the rat superior cervical ganglion. AB - 1. Using an extracellular recording technique, we have investigated the site of action of adenosine and muscarine on the rat superior cervical ganglion (SCG). The adenosine-induced hyperpolarization and muscarine-induced depolarization of ganglia were localized to the cell bodies of the ganglia. Responses to muscarine and adenosine were larger when recorded via the internal carotid nerve (ICN) compared with the external carotid nerve. Depression of the response to muscarine by adenosine was similar for both nerve trunks. 2. The effects of adenosine and cyclic nucleotides on the d.c. potential and the depolarization to muscarine were examined by recording via the ICN. Adenosine at concentrations up to 1 mM produced concentration-dependent hyperpolarizations. Hyperpolarization induced by 100 microM adenosine was unaffected by 1 microM tetrodotoxin or the muscarinic M1 receptor antagonist pirenzepine (0.3 microM). In contrast, hyperpolarizations to 100 microM adenosine were significantly reduced by 10 microM 8-phenytheophylline (55 +/- 7 microV vs 15 +/- 9 microV, P < 0.01, n = 4). Two agents known to increase intracellular cAMP, i.e. 8-bromo-cyclic-adenosine-3'-5' monophosphate (8BrcAMP) and isoprenaline, depolarized ganglia. Depolarizations to 100 nM mucarine were significantly depressed by adenosine (100 microM) by 26 +/- 2% (n = 61), but unaltered by 8BrcAMP or cyclic guanosine-3'-5' monophosphate. 3. Dipyridamole and hydroxy-nitro-benzylthioguanosine (inhibitors of adenosine transport) and erythro-6-amino-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase), potentiated the depression by adenosine of the response to muscarine, and the hyperpolarization to adenosine respectively. However, there was no evidence to support the hypothesis that there was spontaneous release of endogenous adenosine under the conditions of study, as dipyridamole or EHNA did not alter the control d.c. potential or the depolarization to muscarine. 4. It is concluded that the ability of adenosine to hyperpolarize and depress the response of the rat SCG to muscarine is due to the direct activation of postsynaptic somatodendritic P1-purinoceptors and unlikely to be mediated by an increase in intracellular cAMP. In addition the rat SCG has mechanisms for both the uptake and inactivation of adenosine. PMID- 8514825 TI - [Cholecystectomy under celioscopy: does a new approach herald the decline of ancient dogmas?]. PMID- 8514826 TI - [Strangled paracecal ileo-appendicular hernia]. PMID- 8514827 TI - [A curious appendicitis: hemoperitoneum by hematocolpos and hematometra]. PMID- 8514828 TI - [Single and multifactorial prognostic study of 400 operated rectal adenocarcinomas]. AB - From 1976 to 1988, 496 patients with rectal adenocarcinoma have been treated at Gustave-Roussy Institute. There were 258 men (52%) and 238 women (48) with a median age of 61 years. Sixty pts (12%) had local treatment (contact-therapy or electro-resection). Thirty six pts (8.25%) had a simple exploration with colostomy. Four hundred pts had a resection: 202 abdomino-perineal resection, 7 perineal resection, 167 anterior resection, and 24 Hartmann's technique. Post operative mortality was 1% (4 pts). Among these 400 pts, 208 had no complementary treatment, 134 had pre +/- post-operative radiotherapy and 58 had post-operative radiotherapy. Sixty one pts had palliative resection. The actuarial survival of the 400 pts at 3, 5 and 10 years are respectively 65%, 51% and 37.5%. The number of lost to follow-up patients was 11 (2.5%) at 5 years and 24 (5.5%) at 10 years. A retrospective uni and multifactorial analysis of the clinical, biological and histopathological data of the 400 pts was done, 18 factors were studied. Our judgement criterion was 5 year survival. The uni-factorial analysis showed 7 variables which had great influence on survival: age > 60 (p = 0.001), signs of severe illness (p < 0.0001), curative or palliative criterion of the surgery (p = 0.0001), depth of invasion (p = 0.0001), lymph node invasion (p = 0.0001), neural invasion (p = 0.0001) and positive emboli (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514829 TI - [The axillopectoral muscle]. AB - Extending between the pectoralis major and latissimus dorsi muscles, the "pectoro axillary" muscle, the principal anatomic variation of the axillary wall, forms and ectopic muscle band that can complicate axillary dissection. The origin and features of this supernumerary muscle related to Langer's arch are described with emphasis on its surgical applications. PMID- 8514830 TI - [The so-called "celio-mesenteric button-hole" region, an anatomico-surgical study]. AB - Average biometric values of the abdominal aorta and its collaterals, together with their variations, were studied during 80 multiple organ biopsies and 60 cadaver dissections. Two morphotypes were detected raising technical and tactical problems during multiple organ biopsies, particularly since this region includes the origin of the renal arteries. The left transplexic approach provides enhanced safety during control of arterial ostia. PMID- 8514831 TI - [Acute necrotic pancreatitis secondary to asparaginase. Role of drug combinations -early diagnosis and treatment. Apropos of 2 cases]. AB - Acute necrotic pancreatitis was diagnosed in two patients treated with asparaginase for, in the first case a highly malignant lymphoma and in the second an acute lymphoblastic leukemia. The diagnosis on clinical findings and amylase assay results was confirmed by LDH and/or C reactive protein values and abdominal CT scans. Both patients recovered after drainage of peripancreatic fluid collections, in the first patient by surgical followed by cutaneous drainage and in the second by cutaneous drainage of a pancreatic pseudocyst. In addition to the frequent pancreatic reaction observed during asparaginase treatment, signs of pancreatic necrosis requiring urgent treatment have to be identified. The necrotic nature of the pancreatitis was confirmed by clinical examination, assay to biologic markers and abdominal CT scans, eliminating other causes of the pancreatitis. PMID- 8514832 TI - [Quality control of care in a surgical department. Experience of the Fondation Berganie]. AB - Activity in a surgical department can be evaluated quantitatively, but is should also be assessed qualitatively. One way to control the quality of care is to determine as accurately as possible the incidence of pre- peri- and post operative complications and to analyse these date in a critical comparative study. This was accomplished in the surgical department of the Fondation Bergonie, Bordeaux during three test periods over the last five years--March 1987 (127 patients), June-July 1989 (276 patients), and June 1991 (147 patients). Results of this analysis cannot validly be compared with those of other departments with different patient recruitment and activity functions. However, this study within a department with regular, homogeneous activity did demonstrate, over a period of several years, a clear reduction in operative mortality, essentially by improved control of infectious complications by the extensive use of prophylactic antibiotic therapy for all surgery with a septic risk or for debilitated patients. Results also demonstrated the low cost effectiveness of routine pre-operative exploratory examinations. PMID- 8514833 TI - [Mesenteric cystic lymphangioma associated with necrosis of the Bauhin's valvula in children]. AB - Mesenteric Cystic Lymphangiomas is a rare benign tumor. The first case was described after an autopsy in 1507 by Benivieni, an anatomist from Florence. In 1880 by Tillaux. Since then many cases have been described. None of these cases is associated with a non specific necrosis due to Bauhins' valvula compression; in the following lines we are going to describe this exceptional case. PMID- 8514834 TI - [Crohn's disease of the small intestine: place of surgery in 1992]. AB - Crohn's disease (CD) is a chronic pan-enteric inflammatory disease of unknown etiology. Although treatment of CD of small intestine is at present principally medical, in the majority of cases surgical intervention is unavoidable, essentially to treat complications such as occlusion, intra- and/or extra abdominal abscess, certain fistulae, intraperitoneal perforation, profuse hemorrhage and neoplastic degeneration. Surgery may also be indicated during acute episodes of corticotherapy resistant CD, and as a valid alternative to only partially effective long term corticoid treatment of an active chronic disease. Experience has shown that surgery should be as conservative as possible, "stricturoplasty" being the treatment of choice for stenotic lesions. Postoperative follow-up conditions have still to be formulated because of the marked variations in manifestations of recurrence of the disease. PMID- 8514835 TI - [Therapeutic aspects of perforated colorectal cancers]. PMID- 8514836 TI - Selective on-line enrichment and separation of peptides having aromatic amino acids at their C-termini by column-switching high-performance liquid chromatography using an anhydrochymotrypsin-immobilized precolumn. AB - A column switching high-performance liquid chromatographic system in which peptides retained on an anhydrochymotrypsin (AHC)-immobilized diol-silica precolumn were selectively transferred to and separated on a reversed-phase analytical column was developed. An investigation of the affinity characteristics of 40 peptides to the AHC precolumn showed that among eleven peptides having Tyr or Phe at their C-termini and more than five amino acid residues, ten were retained almost quantitatively on the precolumn, and two peptides having Trp at their C-termini were less retained. Two peptides having C-terminal PheNH2 were also retained, but the peptide having C-terminal D-PheNH2 was not retained. Among eighteen peptides having no aromatic amino acids at their C-termini, two were retained, one slightly and the other moderately. Calibration graphs for rat atrial natriuretic peptide constructed at various sample sizes were nearly identical, indicating that the peptide could be enriched by this system. The AHC precolumn showed no loss of analytical performance over 1 year, during which about 450 samples were analysed. PMID- 8514837 TI - Determination of amino sugars in synthetic glycopeptides during the conditions of amino acid analysis utilizing precolumn derivatization and high-performance liquid chromatographic analysis. AB - The growing number of synthetic glycopeptides required an in-house method for the analysis of the final products. A reversed-phase high-performance liquid chromatographic protocol was developed to verify the presence of N acetylglucosamine and N-acetylgalactosamine in synthetic glycopeptides after hydrolysis and derivatization with 4-dimethylaminoazobenzene-4'-sulphonyl chloride. Different sugar and glycoamino acid standards were used to separate the two carbohydrate moieties, and the location of the derivatized 2-aminoglucose was established by the use of radiolabeled sugar. The utility of the approach is demonstrated by the amino acid analysis of N- and O-glycosylated synthetic peptides and the method could provide an alternative for sugar analysis of glycoproteins. PMID- 8514838 TI - Blocking ELISA for detection of mumps virus antibodies in human sera. AB - A new blocking enzyme-linked immunosorbent assay (ELISA) for detection of mumps virus (MuV) specific antibodies in large numbers of human serum samples was developed. The blocking ELISA is based on the reaction of MuV-specific, conjugated monoclonal antibodies (mAbs) with immobilized virus antigen, that has previously been incubated with a two-fold dilution of human serum. Mouse hybridomas that produce antibodies against MuV proteins were generated. They could be divided into 4 groups according to their hemagglutination inhibiting- and virus neutralizing capacities and their reaction in the blocking ELISA with MuV strain Enders. Ascites material from 22 mAbs derived from the 4 groups was further characterized with the MuV strains Enders and Jeryl Lynn. When mAbs from different groups were mixed in the blocking ELISA, an additional increase in absorbance could be observed. A mixture of 2 MuV neutralizing mAbs that were directed against HN and F protein, was used to assay 3 consecutive pre-, early post- and late postvaccination serum samples of 138 children, vaccinated at the age of 1.5 yr. A correlation of 94% was found between the blocking ELISA and the normal indirect ELISA, and of 98% between the blocking ELISA and the neutralization enzyme immunoassay (N50-EIA). The specificity and rapidity of the blocking ELISA makes it suitable for routine use in the determination of MuV neutralizing antibodies in large quantities of serum samples. PMID- 8514839 TI - Biochemical and immunological characterization of micellar complexes of the envelope glycoprotein of a simian immunodeficiency virus isolated from an African green monkey. AB - The external envelope glycoprotein gp130 of a simian immunodeficiency virus isolated from an African green monkey (SIVagmTYO-7) was purified as micellar complexes. The molecular weight of the gp130 micelles was about 700 K. On electron microscopy, the micelles appeared as spherical particles with a diameter of 15 to 20 nm. Such aggregates consisted of about 4 to 5 gp130 monomers. Hyperimmune sera raised in rabbits and rhesus monkeys against these gp130 micelles exhibited titers between 10(5) and 10(6). Such sera inhibit the CD4 binding of gp130 and neutralize SIVagmTYO-7 and SIVmac251 but not HIV-2ben. PMID- 8514840 TI - A procedure for the isolation of specific point mutants of influenza virus. AB - Procedures were developed for the screening and isolation of RNA viruses that vary from the consensus population by a single point mutation and are present in low abundance. We tested these procedures using a mixture of the vaccine donor line cold-adapted (ca) B/Ann Arbor/1/66 and its wild type (wt) progenitor at a ratio of 1,000:1. A 13-mer oligodeoxynucleotide was prepared as a [32P] radiolabeled probe which specifically hybridized to wt viral RNA (vRNA) at a region that varied between the ca and wt sequence by a single base at position 1,320 of the PA gene. This probe was able to detect as little as 88 pg of total wt vRNA blotted to nitrocellulose, while giving no positive signal with as much as 1 microgram of total ca vRNA. We were able to isolate virus containing the wt PA gene sequence from the mixed pool of ca and wt viruses by two successive rounds of amplification in embryonated eggs inoculated with a controlled number of infectious virions. During each round of amplification the abundance of the virus containing the wt PA gene sequence was increased about ten-fold. Once a relative abundance of 1:10 was reached, the virus was cloned by plaquing in Madin Darby canine kidney cells. These procedures, which allow the isolation of specific point mutants, utilize no selective pressure conditions and are suitable for analyzing the phenotypic importance of known mutations in biologically important viruses. PMID- 8514841 TI - A simple and efficient procedure for the oral inoculation of Trichoplusia ni larvae with polyhedrin-negative recombinant baculovirus. AB - Current procedures for inoculating lepidopteran larvae with polyhedrin-negative recombinant baculovirus, i.e. intracoelomic injection or coinfection with wild type virus, are laborious and can compromise final yields of recombinant protein. Herein is described a simple and efficient method for oral inoculation. Up to 100% infection was obtained when individual early fifth instar Trichoplusia ni larvae were fed a small piece of a formaldehyde-free insect diet to which 4.2 x 10(5) PFU of a polyhedrin-negative recombinant Autographa californica nuclear polyhedrosis virus (AcNPV) containing the gene for beta-galactosidase was applied. Infected larvae were identified by assaying hemolymph for beta galactosidase activity. The maximum levels of beta-galactosidase detected in these hemolymph samples were identical to those obtained for larvae infected by intracoelomic injection. The dose of polyhedrin-negative recombinant virus recommended for intracoelomic injection of T. ni was efficacious for the oral route of inoculation. PMID- 8514842 TI - Transfection of whole plants from wounds inoculated with Agrobacterium tumefaciens containing cDNA of tobacco mosaic virus. AB - We engineered cDNA of tobacco mosaic tobamovirus (TMV) into Agrobacterium tumefaciens for inoculation of plant cells. The resulting bacterial strains were used to transfect tobacco (Nicotiana tabacum cv. Xanthi and Xanthi/nc) with wild type and a defective virus. Lesion formation on Xanthi/nc tobacco was used to measure the timing and efficiency of transfection. Infections mediated by Agrobacterium produced lesions an average of two days later than infections produced by inoculation with virions. The addition of approximately 80 bp of non viral sequences to the 5'-end of TMV transcripts abolished transfection. Transcripts with non-viral sequences at the 3'-end initiated infections, while precise transcript termination with a synthetic ribozyme sequence increased transfection frequencies two-fold. Culture conditions reported to induce genes of the vir region of the Agrobacterium Ti plasmid also increased the transfection frequency approximately two-fold. Therefore, in addition to the pararetroviruses and geminiviruses previously described, 'agroinoculation' may be used to infect plants with plus-sense RNA viruses. PMID- 8514843 TI - Suppression of the inhibitory effect of denatured albumin on the polymerase chain reaction by sodium octanoate: application to routine clinical detection of hepatitis B virus at its infectivity threshold in serum. AB - Ten to fifteen percent of posttransfusion viral hepatitis cases are still caused by HBV despite mandatory third generation screening procedures for HBsAg. There is thus an urgent need for a simple, time-cost-effective, but very sensitive test for routine HBV DNA detection in serum. Nested-primed PCR has been shown to detect purified HBV DNA at its infectivity threshold in serum. Since this is too labor-intensive for routine testing, we assessed the efficiency of a Fast PCR procedure, of three pairs of primers, and of thirty-five simple serum pretreatments with the aim to achieve the same sensitivity level. Using ten-fold dilution in phosphate buffered saline as pretreatment and Fast PCR for 99 cycles, we were able to detect HBV DNA at the 2 x 10(3)/ml level in serum. Using either NaOH denaturation or sodium octanoate thermoprotection as pretreatment and Fast PCR for 99 cycles, we were able to detect HBV DNA at its infectivity threshold in serum, while the classical phenol/chloroform/isoamylic alcohol/isopropanol/ethanol DNA purification procedure enabled us to reach the 10 virus particles/ml level. These results suggest that denatured albumin is responsible for the well known inhibitory effect of serum proteins on Taq polymerase. Because of its simplicity and its lower risk of sample-to-sample cross-contamination, the sodium octanoate thermoprotection method was chosen for routine clinical detection of HBV in serum. The clinical usefulness of this approach is demonstrated by the results obtained with HBsAg-negative acute hepatitis B incubation sera and with anti HBe-positive chronic hepatitis B sera. PMID- 8514844 TI - Primer extension analysis provides a sensitive tool for the identification of PCR amplified DNA from HIV-1. AB - Primer extension analysis was evaluated as a means to identify PCR-amplified DNA from HIV-1. Solution hybridization with radioactive labeled oligonucleotides followed by an extension reaction with Klenow fragment of Escherichia coli DNA polymerase I and subsequent separation on denaturing polyacrylamide gels reveals single stranded DNA products of the predicted size. The specificity of the reaction is further demonstrated by specific endonuclease digestion. The analysis is more sensitive than Southern blotting and about equally sensitive as Slot blot analysis when double-stranded DNA probes are used for hybridization. With end labeled oligonucleotide probes, primer extension analysis proved an order of magnitude more sensitive than membrane hybridization. The analysis also allows quantitation of amplified DNA from 1 pg to about 1 ng of DNA product. Under the conditions described for amplification, primer extension analysis is capable of detecting a single HIV-1 plasmid DNA molecule in the presence of 1 microgram of total DNA. 3'-end mismatching of the oligonucleotide probe does not result in a significantly altered detection limit. Primer extension analysis can also be carried out with at least three different PCR-amplified DNAs in the same reaction tube. PMID- 8514845 TI - Direct cloning and expression of PCR amplified DNA and RNA sequences: application to the hepadnaviruses nucleocapsid proteins. AB - Gene amplification may benefit from the construction of primers that augments the speed at which cloning and protein expression proceeds. Such primers include EcoRI or HindIII linkers as well as an in phase initiation or termination codon. PCR was carried out directly from viral particles of human hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV) without DNA purification and from RNA extracted from WHV infected liver. Amplified products were directly cloned in the pKK223-3 expression vector under the control of the tac promoter. The characterization of the recombinant clones expressing the nucleocapsid protein (C protein) was done by direct incubation of the filter with 125I-labelled anti-HBc and confirmed by radioimmunoassay and Western-blot analysis. This procedure allows easy selection of recombinant clones expressing a given protein and could be applied to many other genes. PMID- 8514846 TI - Reappraisal of modified neutralization test for Inoue-Melnick virus. AB - Ito et al. (1992) reported an improved modification of the neutralization (NT) test for Inoue-Melnick Virus (IMV) by prolonged 90 min incubation of the mixture of the virus and serum. For confirmation, we compared the results of the NT test by 90 and 60 min incubation. Against human sera, the NT test by 90 min incubation was significantly more sensitive than the test by 60 min incubation. By 90 min incubation, the NT titers increased by 3 to 6 times and approximately 6% of antibody-negative adult sera previously determined in the tests by 60 min incubation turned to positive (more than 1:10). However, antibody-negative sera of Japanese children examined previously in the tests by 60 min incubation remained negative after the 90 min tests. On the other hand, against rabbit immune sera, no significant difference of NT titers was observed between the two NT tests for 90 and 60 min incubation. Also we reinvestigated Japanese adult sera for type 2 IMV infection by the NT test for 90 min incubation, but did not find any serum of type 2 or intermediate type infection. Therefore, it is not necessary to change the previous conclusion that in Japan IMV infections are mostly of type 1. PMID- 8514847 TI - The genetic basis of X-linked nephrolithiasis: leaving no stone unturned. PMID- 8514848 TI - Misguided leukocyte adhesion. PMID- 8514849 TI - Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus. AB - In patients with non-insulin-dependent diabetes mellitus (NIDDM) and matched control subjects we examined the interrelationships between in vivo nonoxidative glucose metabolism and glucose oxidation and the muscle activities, as well as the immunoreactive protein and mRNA levels of the rate-limiting enzymes in glycogen synthesis and glycolysis, glycogen synthase (GS) and phosphofructokinase (PFK), respectively. Analysis of biopsies of quadriceps muscle from 19 NIDDM patients and 19 control subjects showed in the basal state a 30% decrease (P < 0.005) in total GS activity and a 38% decrease (P < 0.001) in GS mRNA/microgram DNA in NIDDM patients, whereas the GS protein level was normal. The enzymatic activity and protein and mRNA levels of PFK were all normal in diabetic patients. In subgroups of NIDDM patients and control subjects an insulin-glucose clamp in combination with indirect calorimetry was performed. The rate of insulin stimulated nonoxidative glucose metabolism was decreased by 47% (P < 0.005) in NIDDM patients, whereas the glucose oxidation rate was normal. The PFK activity, protein level, and mRNA/microgram DNA remained unchanged. The relative activation of GS by glucose-6-phosphate was 33% lower (P < 0.02), whereas GS mRNA/micrograms DNA was 37% lower (P < 0.05) in the diabetic patients after 4 h of hyperinsulinemia. Total GS immunoreactive mass remained normal. In conclusion, qualitative but not quantitative posttranslational abnormalities of the GS protein in muscle determine the reduced insulin-stimulated nonoxidative glucose metabolism in NIDDM. PMID- 8514850 TI - Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages. AB - Macrophages participate in inflammatory and repair processes in part through the selective release of cytokines that contribute to tissue remodeling. Extracellular matrix components generated at inflammatory sites may influence tissue remodeling by effects on leukocyte adherence and local cytokine production. In murine bone marrow-derived macrophages, we found that soluble hyaluronic acid stimulated IL-1 beta, TNF alpha, and insulin-like growth factor-1 (IGF-1) mRNA transcript expression as well as IGF-1 protein synthesis. Monoclonal antibodies to the hyaluronic acid receptor CD44 blocked the effects of hyaluronic acid on IL-1 beta, TNF alpha, and IGF-1 expression. TNF alpha and IL-1 beta mRNA expression preceded IGF-1 protein synthesis, and TNF alpha, but not IL-1 beta, was found to directly stimulate IGF-1. Furthermore, IGF-1 induction was dependent on endogenous TNF alpha production since IGF-1 protein synthesis was inhibited in the presence of anti-TNF alpha antiserum. In addition, IL-1 beta was found to exert a regulatory role on IGF-1 production by enhancing the TNF alpha effect. IL 1 beta and TNF alpha mRNA transcript expression as well as IGF-1 protein synthesis were also stimulated by chrysotile asbestos. Anti-CD44 antibodies had no effect whereas anti-TNF alpha antiserum blocked asbestos-stimulated IGF-1 production. These results indicate that hyaluronate activation of CD44 induces cytokine expression and macrophage-derived IGF-1 production is dependent on TNF alpha expression. PMID- 8514851 TI - Characterization of adhesive interactions between human endothelial cells and megakaryocytes. AB - Cell-cell adhesion is essential for many immunological functions and is believed to be important in the regulation of hematopoiesis. Adhesive interactions between human endothelial cells and megakaryocytes were characterized in vitro using the CMK megakaryocytic cell line as well as marrow megakaryocytes. Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion. Stimulation of marrow megakaryocytes or CMK cells with the cytokines IL 1 beta, GM-CSF, IL-6, IL-3, or PMA augmented their adhesion to endothelium. Monoclonal antibodies against the LFA-1 subunit of the leukocyte adherence complex CD18 inhibited the binding of marrow megakaryocytes or CMK cells to HUVEC. Adhesion blocking experiments also demonstrated that the VLA-4/VCAM-1 pathway was important for megakaryocyte attachment to HUVEC. Adhesion promoted maturation of megakaryocytic cells as measured by increased expression of glycoproteins GpIb and GpIIb/IIIa and by increased DNA content. These observations suggest that alterations in megakaryocyte adhesion may occur during inflammatory conditions, mediated by certain cytokines, resulting in augmented megakaryocyte maturation. PMID- 8514852 TI - Protective protein gene mutations in galactosialidosis. AB - Four different protective protein cDNA mutations, 146A-->G (Q49R), 193T-->C (W65R), 268-269TC-->CT (S90L), and 1184A-->G (Y395C), were identified in six Japanese galactosialidosis patients with various phenotypic manifestations, and another mutation, 746T-->A (Y249N), in a patient of French-German origin with an atypical clinical course. Y395C was a common mutation in four Japanese patients in infancy and childhood; two juvenile patients were compound heterozygotes of Y395C and another common mutation, SpDEx7, and the other two infants were compound heterozygotes of Y395C and mutant alleles other than SpDEx7. We confirmed these mutations in genomic DNA by direct-sequence analysis or restriction-site analysis. The mutant cDNA clones, transiently expressed in a transformed galactosialidosis cell line, did not restore the secondarily deficient beta-galactosidase or alpha-neuraminidase activity except for the Y249N mutation that expressed some carboxypeptidase activity and restored the two lysosomal enzyme activities. Pulse-chase analysis detected a small amount of the mature form, as well as the precursor, in the cells transfected with the Y249N cDNA. Only precursor proteins were detected, mature proteins not appearing for the other mutant cDNAs. PMID- 8514853 TI - Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families. AB - Generalized resistance to thyroid hormone (GRTH) is a syndrome of variable reduction of tissue responsiveness to thyroid hormone. 28 different point mutations in the human thyroid hormone receptor beta (TR beta) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TR beta (codons 310-347 and 417-453). We now report point mutations in the TR beta gene of six additional families with GRTH and show that three mutations occurred each in three families with GRTH, and that three other mutations were each present in two families. In 11 of these 15 families, lack of a common ancestor could be confirmed by genetic analysis. 28 of the 38 point mutations so far identified, including all those occurring in more than one family, are located in cytosine-guanine-rich areas of the TR beta gene. Differences in clinical and laboratory findings in unrelated families harboring the same TR beta mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action. PMID- 8514854 TI - A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo. AB - We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production and on the development of hypercalcemia in Fischer rats implanted with the Leydig cell tumor H-500. Leydig cell tumors were implanted subcutaneously into male Fischer rats, which received constant infusions intraperitoneally of either 1,25(OH)2D3 (50-200 pmol/24 h), EB1089 (50-400 pmol/24 h), or vehicle for up to 4 wk. A control group of animals received similar infusions without tumor implantation. Plasma calcium, plasma levels of immunoreactive iPTHRP, and tumor PTHRP mRNA levels were determined as well as tumor size, animal body weight, and animal survival time. Non-tumor-bearing animals receiving > 50 pmol/24 h of 1,25(OH)2D3 became hypercalcemic, whereas no significant change in plasma calcium was observed in animals receiving < or = 200 pmol/24 h of EB1089. Tumor-bearing animals receiving vehicle alone or > 50 pmol/24 h of 1,25(OH)2D3 became severely hypercalcemic within 15 d. However, animals treated with low dose 1,25(OH)2D3 and all doses of EB1089 maintained near-normal or normal levels of plasma calcium for up to 4 wk. Additionally, reduced levels of tumor PTHRP mRNA and of plasma iPTHRP were observed compared with controls in both vitamin D- and EB1089-treated rats. Infusion of 50 pmol/24 h of 1,25(OH)2D3 and 200 pmol/24 h of EB1089 significantly reduced tumor volume by the end of experiment. The analogue but not 1,25(OH)2D3 substantially prolonged survival time in tumor-bearing animals with longer survival achieved at the highest dose, 400 pmol/24 h, of EB1089. These studies demonstrate that 1,25(OH)2D3 and a low calcemic vitamin D analogue are potent inhibitors of PTHRP production in vivo. Low calcemic analogues may therefore represent important alternative therapy for malignancy-associated hypercalcemia. PMID- 8514855 TI - The effect of hemodialysis on protein metabolism. A leucine kinetic study. AB - To assess the effect of hemodialysis on protein metabolism, leucine flux was measured in seven patients before, during, and after high efficiency hemodialysis using cuprophane dialyzers and bicarbonate dialysate during a primed-constant infusion of L-[1-13C]leucine. The kinetics [mumol/kg per h, mean +/- SD] are as follows: leucine appearance into the plasma leucine pool was 86 +/- 28, 80 +/- 28, and 85 +/- 25, respectively, before, during, and after dialysis. Leucine appearance into the whole body leucine pool, derived from plasma [1-13C]alpha ketoisocaproate enrichment, was 118 +/- 31, 118 +/- 31, and 114 +/- 28 before, during, and after dialysis, respectively. In the absence of leucine intake, appearance rate reflects protein degradation, which was clearly unaffected by dialysis. Leucine oxidation rate was 17.3 +/- 7.8 before, decreased to 13.8 +/- 7.8 during, and increased to 18.9 +/- 10.3 after dialysis (P = 0.027). Leucine protein incorporation was 101 +/- 26 before, was reduced to 89 +/- 23 during, and returned to 95 +/- 23 after dialysis (P = 0.13). Leucine net balance, the difference between leucine protein incorporation and leucine release from endogenous degradation, was -17.3 +/- 7.8 before, decreased to -28.5 +/- 11.0 during, and returned to -18.9 +/- 10.3 after dialysis (P < 0.0001). This markedly more negative leucine balance during dialysis was accountable by dialysate leucine loss, which was 14.4 +/- 6.2 mumol/kg per h. These data suggest that hemodialysis using a cuprophane membrane did not acutely induce protein degradation. It was, nevertheless, a net catabolic event because protein synthesis was reduced and amino acid was lost into the dialysate. PMID- 8514856 TI - Short-term effects of tumor necrosis factor on energy and substrate metabolism in dogs. AB - In vivo short-term effects of recombinant human TNF-alpha on lipolysis, FFA flux, fat oxidation, triglyceride-fatty acid cycling, and glucose kinetics were evaluated with stable isotopic tracers and indirect calorimetry along with monitoring of hemodynamic parameters in fasted dogs. High-dose TNF infusion (10 micrograms/kg) caused a fall in mean arterial pressure (P < 0.01), pulmonary arterial pressure (P < 0.001), and cardiac index (CI) (P < 0.05). The rate of appearance of glycerol (Ra glycerol) and the rate of appearance of FFA (Ra FFA) were decreased by 20% (P < 0.05) and by 42% (P < 0.01), respectively. Total fat oxidation fell by 23% (P < 0.05). In contrast, TNF infusion significantly increased glucose production by 13% (P < 0.05) and metabolic clearance rate of glucose by 25% (P < 0.01). However, TNF infusion did not change energy expenditure. Low-dose TNF infusion (3.5 micrograms/kg) caused changes similar in all respects, except magnitude, to the high-dose effects. There was a significant correlation between percent change of CI (delta CI) and percent change of rate of appearance of palmitate (Ra palmitate; delta Ra palmitate) (P < 0.0001, r = 0.69), Ra FFA (delta Ra FFA) (P < 0.0001, r = 0.60), and Ra glycerol (delta Ra glycerol) (P < 0.0329, r = 0.36). The correlation between delta CI and delta Ra palmitate was greater than the correlation between delta CI and delta Ra glycerol (P = 0.028). We conclude that the acute response to TNF causes a shift towards carbohydrate as an energy substrate in a dose-dependent manner by both decreasing the availability of FFAs and increasing glucose production. PMID- 8514857 TI - A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. AB - To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions. PMID- 8514858 TI - Accumulation of Maillard reaction products in skin collagen in diabetes and aging. AB - To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon (carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins. PMID- 8514859 TI - Maillard reaction products and their relation to complications in insulin dependent diabetes mellitus. AB - Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01 1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy. PMID- 8514860 TI - Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol. AB - To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis. PMID- 8514861 TI - Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin. AB - The sterol 27-hydroxylase (EC 1.14.13.15) catalyzes steps in the oxidation of sterol intermediates that form bile acids. Mutations in this gene give rise to the autosomal recessive disease cerebrotendinous xanthomatosis (CTX). CTX is characterized by tendon xanthomas, cataracts, a multitude of neurological manifestations, and premature atherosclerosis. A relatively high prevalence of the disease has been noted in Jews originating from Morocco. The major objectives of the present investigation were to determine the gene structure and characterize the common mutant alleles that cause CTX in Moroccan Jews. The gene contains nine exons and eight introns and encompasses at least 18.6 kb of DNA. The putative promoter region is rich in guanidine and cytosine residues and contains potential binding sites for the transcription factor Sp1 and the liver transcription factor, LF-B1. Blotting analysis revealed that the mutant alleles do not produce any detectable sterol 27-hydroxylase mRNA. No major gene rearrangements were found and single-strand conformational polymorphism followed by sequence analysis identified two underlying mutations: deletion of thymidine in exon 4 and a guanosine to adenosine substitution at the 3' splice acceptor site of intron 4 of the gene. The molecular characterization of CTX in Jews of Moroccan origin provides a definitive diagnosis of this treatable disease. PMID- 8514862 TI - Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure. Evidence for high levels of the natural inhibitor S adenosylhomocysteine. AB - The enzyme protein carboxyl methyltransferase type II has been recently shown to play a crucial role in the repair of damaged proteins. S-adenosylmethionine (AdoMet) is the methyl donor of the reaction, and its demethylated product, S adenosylhomocysteine (AdoHcy), is the natural inhibitor of this reaction, as well as of most AdoMet-dependent methylations. We examined erythrocyte membrane protein methyl esterification in chronic renal failure (CRF) patients on conservative treatment or hemodialyzed to detect possible alterations of the methylation pattern, in a condition where a state of disrupted red blood cell function is present. We observed a significant reduction in membrane protein methyl esterification in both groups, compared to control. The decrease was particularly evident for cytoskeletal component ankyrin, which is known to be involved in membrane stability and integrity. Moreover, we observed a severalfold rise in AdoHcy levels, while AdoMet concentration was comparable to that detected in the control, resulting in a lower [AdoMet]/[AdoHcy] ratio (P < 0.001). Our findings show an impairment of this posttranslational modification of proteins, associated with high AdoHcy intracellular concentration in CRF. The data are consistent with the notion that, in CRF, structural damages accumulate in erythrocyte membrane proteins, and are not adequately repaired. PMID- 8514863 TI - Isolation of a human myocardial cytosolic phospholipase A2 isoform. Fast atom bombardment mass spectroscopic and reverse-phase high pressure liquid chromatography identification of choline and ethanolamine glycerophospholipid substrates. AB - Recent studies have demonstrated the existence of a novel family of calcium independent plasmalogen-selective phospholipases A2 in canine myocardium that have been implicated as enzymic mediators of ischemic membrane damage. We now report that human myocardium contains two functionally distinct isoforms of cytosolic calcium-independent phospholipase A2. The major cytosolic phospholipase A2 isoform preferentially hydrolyzes plasmalogen substrate, possesses a pH optimum of 7.0, and is chromatographically resolvable from a minor cytosolic calcium-independent phospholipase A2 isoform that hydrolyzes plasmenylcholine and phosphatidylcholine substrates at similar rates and possesses a pH optimum of 8.5. The major cytosolic calcium-independent phospholipase A2 isoform was identified as a 40-kD polypeptide after its 182,000-fold purification by sequential column chromatographies to a final specific activity of 67 mumol/mg.min. The purified 40-kD human myocardial phospholipase A2 preferentially hydrolyzes plasmalogens containing arachidonic acid at the sn-2 position. Both reverse-phase HPLC and fast atom bombardment mass spectroscopic analysis of human myocardial ethanolamine and choline glycerophospholipids demonstrated that plasmenylethanolamine and plasmenylcholine molecular species containing arachidonic acid at the sn-2 position are prominent constituents of human myocardium. Collectively, these results identify and characterize the major human myocardial cytosolic calcium-independent phospholipase A2 activity, demonstrate the presence of functionally distinct human myocardial cytosolic calcium independent phospholipase A2 isoforms, and document the abundance of arachidonoylated plasmalogen molecular species in human myocardium that serve as substrates. PMID- 8514864 TI - Regulation of follistatin messenger ribonucleic acid levels in the rat pituitary. AB - Follistatin is a glycoprotein, originally isolated from the gonads, that specifically inhibits follicle-stimulating hormone (FSH) biosynthesis and secretion. We have previously detected follistatin mRNA in rat pituitary gonadotropes. To assess the potential physiologic role of follistatin in the rat pituitary, we have investigated the effects of gonadectomy (GDX) and of sex steroid replacement on pituitary follistatin gene expression. Follistatin mRNA levels in individual rat pituitaries were measured by a quantitative reverse transcription-polymerase chain reaction assay. Female and male rats 21 d old underwent surgical GDX and were then killed 21 d after GDX. Follistatin mRNA levels in rat pituitary increased 3.2 +/- 1.5-fold (P < 0.01) in GDX female rats and 8.2 +/- 2.0-fold (P < 0.005) in GDX male rats, compared with intact female and male controls, respectively. Replacement therapy with 17 beta-estradiol-3 benzoate (10 micrograms/100 g body weight) subcutaneously daily for 7 d in GDX female rats resulted in a slight further increase in follistatin mRNA levels compared to GDX females. In contrast, therapy with testosterone propionate (500 micrograms/100 g body weight) subcutaneously daily for 7 d in GDX male rats resulted in a decrease in follistatin mRNA levels, towards but not completely back to baseline levels in intact males. Time-course studies in adult male and female rats showed that the increase in follistatin mRNA levels after GDX is rapid, with significant increases occurring within 24 h after GDX, and parallels or precedes increases in FSH beta mRNA levels and FSH secretion. The regulation of follistatin mRNA levels in the rat pituitary by GDX and by sex steroids suggests that follistatin may be important as an autocrine or paracrine factor in the regulation of FSH. PMID- 8514865 TI - Plasma lipoproteins after triglyceride clearance in cholesterol-fed rats. AB - The clearance of particulate triglyceride from the plasma of cholesterol-fed rats with appreciable stores of hepatic cholesterol ester produces a substantial increment in plasma cholesterol. Most of this plasma cholesterol increment arises from existing tissue sources. The increment begins from 4 to 6 h after clearance and is due to the appearance of larger cholesterol-rich, triglyceride-poor, beta migrating lipoproteins, which are isolated in the d < 1.063 fraction with an apoprotein (Apo) content consisting primarily of Apo E and smaller amounts of Apo B. A concurrent decrease in alpha lipoproteins occurs with the beta lipoprotein increment. Within 1 d of clearance the beta lipoproteins fall and alpha lipoproteins increase. The increase in total plasma Apo E and Apo B initially parallels that of the cholesterol, but it persists even when cholesterol falls. A modest decrease in plasma Apo A1 was observed during the time alpha lipoproteins declined. A significant increase in plasma lecithin cholesterol acyl transferase preceded the increase in beta lipoprotein cholesterol. This enzyme increment was absent in rats with little lipoprotein response despite increased hepatic cholesterol. In vivo inhibition of this enzyme with dithionitrobenzoic acid virtually eliminated the postclearance hypercholesterolemia. Plasma particulate triglyceride clearance induces an increase in beta lipoproteins. Coupling of this clearance and hepatic lipoprotein secretion occurs by an unknown mechanism modulated by lecithin cholesterol acyl transferase. PMID- 8514866 TI - Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms. AB - Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms. PMID- 8514867 TI - Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase. AB - Autoantibodies to five aminoacyl-tRNA synthetases have been reported, and all have been associated with a syndrome of myositis and interstitial lung disease. Four of these synthetases exist free in the cytoplasm, but the fifth, isoleucyl tRNA synthetase (recognized by anti-OJ autoantibodies), is a component of the multi-enzyme complex containing at least seven synthetases. In an effort to better understand the origins of these antibodies, we examined sera from 11 patients with anti-OJ autoantibodies for evidence of reaction with other components of the complex. All sera showed a characteristic pattern of 10 proteins bands by immunoprecipitation from HeLa cell extract. 10 of 11 sera significantly inhibited isoleucyl-tRNA synthetase enzyme activity. Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase. Immunoblotting experiments supported reaction of the two sera with lysyl-tRNA synthetase, and revealed additional reactivity of three sera with a 160-kD component believed to be glutaminyl-tRNA synthetase. Despite reaction of some sera with additional synthetases, the immunoprecipitated tRNA appeared the same with all sera, and functioned as tRNA(ile). While reaction with more than one synthetase was seen with some anti-OJ sera, all synthetases targeted by anti-OJ sera were components of the complex, rather than unassociated synthetases. These findings suggest that an initial autoantibody response against isoleucyl-tRNA synthetase was followed by extension to involve other components of the synthetase complex. These observations may have implications for understanding the generation of antisynthetase autoantibodies. PMID- 8514868 TI - Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus. AB - A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals. PMID- 8514869 TI - Genetic control of inflammatory gene induction and NF-kappa B-like transcription factor activation in response to an atherogenic diet in mice. AB - A high fat, high cholesterol "atherogenic" diet induced considerably greater hepatic levels of conjugated dienes and expression of several inflammatory and oxidative stress responsive genes (JE, the mouse homologue of monocyte chemotactic protein-1, colony-stimulating factors, heme oxygenase, and members of the serum amyloid A family) in fatty streak susceptible C57BL/6 mice compared to fatty streak resistant C3H/HeJ mice. Since serum amyloid A proteins bind exclusively to HDL and influence the properties of HDL, serum amyloid A expression may contribute to the decrease in HDL levels seen in the susceptible strains. Induction of a similar set of genes was observed upon injection of minimally oxidized low density lipoprotein. The transcription factor NF-kappa B is known to be activated by oxidative stress and is involved in the transcriptional regulation of several of these genes. On the atherogenic diet the susceptible C57BL/6 mice exhibited significant NF-kappa B-like activation whereas the resistant C3H/HeJ mice exhibited little or no activation. These results are consistent with the hypothesis that the atherogenic diet resulted in the accumulation of oxidized lipids in certain tissues (e.g., liver and arteries) and the resulting inflammatory response to this oxidative stress was genetically determined. PMID- 8514870 TI - The serology of chronic hepatitis B infection revisited. AB - The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays. PMID- 8514871 TI - Multimerin is found in the alpha-granules of resting platelets and is synthesized by a megakaryocytic cell line. AB - In this report, we describe the intracellular localization of multimerin in platelets and its biosynthesis by Dami cells, a megakaryocytic cell line. Immunoelectron microscopy was used to examine frozen thin sections of resting and activated platelets. Multimerin was localized within the platelet alpha-granule in an eccentric position. Within activated platelets, multimerin was found in the surface-connected open cannalicular system and on the external plasma membrane. Light microscopic immunocytochemistry demonstrated multimerin in normal megakaryocytes and in Dami cells after stimulation with PMA. Confirmation of multimerin biosynthesis by Dami cells was obtained by metabolic labeling studies. Both platelet and Dami cell multimerin demonstrated several subunit sizes on reduced SDS-PAGE. However, peptide mapping confirmed structural homology between the different multimerin subunits. Glycosidase digestion demonstrated that multimerin is heavily glycosylated with mainly complex, N-linked carbohydrate. In contrast to the multimerin isolated from platelets, cultured Dami cells secreted mainly smaller multimers of the protein. Biosynthesis of multimerin by a megakaryocytic cell line supports endogenous biosynthesis by megakaryocytes as the origin of this platelet alpha-granule protein. PMID- 8514872 TI - Endothelial cell adhesion in real time. Measurements in vitro by tandem scanning confocal image analysis. AB - Real time measurements of cell-substratum adhesion in endothelial cells were obtained by tandem scanning confocal microscopy of sites of focal contact (focal adhesions) at the abluminal cell surface. Focal contact sites were sharply defined (low radiance levels) in the living cell such that the images could be enhanced, digitized, and isolated from other cellular detail. Sites of focal contact are the principal determinant of cell-substratum adhesion. Measurements of (a) the focal contact area and (b) the closeness of contact (inverse radiance) were used to nominally define the adhesion of a single cell or field of cells, and to record spontaneous and induced changes of cell adhesion in real time. The topography of focal contacts was estimated by calculating separation distances from radiance values using a calibration technique based on interference ring optics. While slightly closer contact was noted between the cell membrane and substratum at or near the center of each focal contact, separation distances throughout the adhesion regions were always < 50 nm. Subtraction of consecutive images revealed continuous spontaneous remodeling of individual focal adhesions in unperturbed cells during periods of < 1 min. Despite extensive remodeling of focal contact sites, however, cell adhesion calculated for an entire cell over extended periods varied by < 10%. When cytoskeletal stability was impaired by exposure to cytochalasin or when cells were exposed to proteolytic enzyme, endothelial adhesion declined rapidly. Such changes were recorded at the level of single cells, groups of cells, and at single focal adhesions. In both unperturbed and manipulated cells, the dynamics of remodeling and cell adhesion characteristics varied greatly between individual sites within the same cell; disappearance of existing sites and appearance of new ones often occurred within minutes while adjacent sites underwent minimal remodelling. Tandem scanning confocal microscopy image analysis of living cells in real time provides repetitive spatial, temporal, and quantitative information about cell adhesion. Such an approach should allow more precise quantitative analyses to be made of the interactions between extracellular matrix, adhesion proteins, integrins, and the cytoskeleton in the living cell. PMID- 8514873 TI - Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2. AB - Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC. PMID- 8514874 TI - Human eosinophils can express the cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha. AB - By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide inhibitable spontaneous release of TNF-alpha in vitro. Many blood eosinophils (39 91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1 alpha mRNA. Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP 1 alpha mRNA. These findings indicate that human eosinophils represent a potential source of TNF-alpha and MIP-1 alpha, that levels of expression of mRNA for both cytokines are high in the blood eosinophils of hypereosinophilic donors and in eosinophils infiltrating nasal polyps, that the eosinophils of normal subjects express higher levels of TNF-alpha than MIP-1 alpha mRNA, and that eosinophils purified from the blood of atopic donors can release TNF-alpha in vitro. PMID- 8514875 TI - Restrictive lung function and asbestos-induced pleural fibrosis. A quantitative approach. AB - To assess further the clinical significance of asbestos-induced pleural fibrosis, we used a computer algorithm to reconstruct images three dimensionally from the high-resolution computerized tomography (HRCT) scan of the chest in 60 asbestos exposed subjects. Pulmonary function tests, chest radiographs, and HRCT scans were performed on all study subjects. The volume of asbestos-induced pleural fibrosis was computed from the three-dimensional reconstruction of the HRCT scan. Among those with pleural fibrosis identified on the HRCT scan (n = 29), the volume of the pleural lesion varied from 0.01% (0.5 ml) and 7.11% (260.4 ml) of the total chest cavity. To investigate the relationship between asbestos-induced pleural fibrosis and restrictive lung function, we compared the computer-derived estimate of pleural fibrosis to the total lung capacity and found that these measures were inversely related (r = -0.40; P = 0.002). After controlling for age, height, pack-years of cigarette smoking, and the presence of interstitial fibrosis on the chest radiograph, the volume of pleural fibrosis identified on the three-dimensional reconstructed image from the HRCT scan was inversely associated with the total lung capacity (P = 0.03) and independently accounted for 9.5% of the variance of this measure of lung volume. These findings further extend the scientific data supporting an independent association between pleural fibrosis and restrictive lung function. PMID- 8514876 TI - Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65. AB - We have shown previously that atherosclerotic lesions can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp65), which has a high degree of sequence homology with mammalian hsp60. To investigate a possible relationship between hsp60 expression and the antigenic specificities of infiltrating T cells in the lesion, 38 New Zealand White rabbits were treated either by immunization with recombinant mycobacterial hsp65 or by administration of a 0.2% cholesterol diet. Atherosclerotic lesions were observed after 16 wk, particularly in the aortic arch and arterial bifurcations of rabbits immunized with hsp65 or fed with a cholesterol-rich diet. Hsp65 staining of aortas showed a heterogeneous distribution, and significantly increased staining intensity in atherosclerotic lesions compared to aortic media or adventitia. This abundantly expressed hsp65 was observed in atherosclerotic lesions induced by hsp65 immunization as well as those induced by cholesterol rich diet alone. Interestingly, a population of the T lymphocytes isolated from all forms of atherosclerotic lesions specifically responded to hsp65 in vitro. IL 2-expanded T cell lines derived from atherosclerotic lesions showed a significantly higher hsp65 reactivity than those developed from peripheral blood of the same donor. Furthermore, levels of circulating antibodies and numbers of spleen cells specifically reacting against hsp65 were elevated in all experimental animals. Flow cytometric analysis of spleen cells showed elevated immune response-associated antigen expression in treated animals. In conclusion, increased hsp65 expression in intimal cells and the presence of hsp65-specific T cells in blood and in atherosclerotic lesions may be important in initiating the development of atherosclerosis and perpetuating the lesions. PMID- 8514877 TI - Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat. AB - The cutaneous permeability barrier to systemic water loss is mediated by hydrophobic lipids forming membrane bilayers within the intercellular domains of the stratum corneum (SC). The barrier emerges during day 20 of gestation in the fetal rat and is correlated with increasing SC thickness and increasing SC lipid content, the appearance of well-formed lamellar bodies in the epidermis, and the presence of lamellar unit structures throughout the SC. Because glucocorticoids accelerate lung lamellar body and surfactant maturation in man and experimental animals, these studies were undertaken to determine whether maternal glucocorticoid treatment accelerates maturation of the epidermal lamellar body secretory system. Maternal rats were injected with betamethasone or saline (control) on days 16-18, and pups were delivered prematurely on day 19. Whereas control pups exhibited immature barriers to transepidermal water loss (8.16 +/- 0.52 mg/cm2 per h), glucocorticoid-treated pups exhibited competent barriers (0.74 +/- 0.14 mg/cm2 per h; P < 0.001). Glucocorticoid treatment also: (a) accelerated maturation of lamellar body and SC membrane ultrastructure; (b) increased SC total lipid content twofold; and (c) increased cholesterol and polar ceramide content three- to sixfold. Thus, glucocorticoids accelerate the functional, morphological, and lipid biochemical maturation of the permeability barrier in the fetal rat. PMID- 8514878 TI - The thyroid gland is a major source of circulating T3 in the rat. AB - In rats, the respective contribution of the thyroid and peripheral tissues to the pool of T3 remains unclear. Most, if not all, of the circulating T3 produced by extrathyroidal sources is generated by 5'-deiodination of T4, catalyzed by the selenoenzyme, type I iodothyronine 5'-deiodinase (5'D-I). 5'D-I in the liver and kidney is almost completely lost in selenium deficiency, resulting in a marked decrease in T4 deiodination and an increase in circulating T4 levels. Surprisingly, circulating T3 levels are only marginally decreased by selenium deficiency. In this study, we used selenium deficiency and thyroidectomy to determine the relative contribution of thyroidal and extrathyroidal sources to the total body pool of T3. Despite maintaining normal serum T4 concentrations in thyroidectomized rats by T4 replacement, serum T3 concentrations remained 55% lower than those seen in intact rats. In intact rats, restricting selenium intake had no effect on circulating T3 concentrations. Decreasing 5'D-I activity in the liver and kidney by > 90% by restricting selenium intake resulted in a further 20% decrease in serum T3 concentrations in the thyroidectomized, T4 replaced rats, suggesting that peripheral T4 to T3 conversion in these tissues generates approximately 20% of the circulating T3 concentrations. While dietary selenium restriction markedly decreased intrahepatic selenium content (> 95%), intrathyroidal selenium content decreased by only 27%. Further, thyroid 5'D-I activity actually increased 25% in the selenium deficient rats, suggesting the continued synthesis of this selenoenzyme over selenoproteins in other tissues in selenium deficiency. These data demonstrate that the thyroid is the major source of T3 in the rat and suggest that intrathyroidal T4 to T3 conversion may account for most of the T3 released by the thyroid. PMID- 8514879 TI - Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver. AB - We investigated the effects of 17 alpha-ethinylestradiol treatment of rats on various transport functions in isolated basolateral and canalicular liver plasma membrane vesicles. Both membrane subfractions were purified to a similar degree from control and cholestatic livers. Although moderate membrane lipid alterations were predominantly observed in basolateral vesicles, no change in basolateral Na+/K(+)-ATPase activity was found. Furthermore, while Na(+)-dependent taurocholate uptake was decreased by approximately 40% in basolateral vesicles, the maximal velocity of ATP-dependent taurocholate transport was decreased by 63% in canalicular membranes. In contrast, only minimal changes or no changes at all were observed for electrogenic taurocholate transport in "cholestatic" canalicular membranes and total microsomes, respectively. However, canalicular vesicles from cholestatic livers also exhibited marked reductions in ATP dependent transport of S-(2,4-dinitrophenyl)glutathione and in Na(+)-dependent uptake of adenosine, while in the same vesicles HCO3-/SO4- exchange and Na+/glycine cotransport activities were markedly stimulated. These data show that in addition to the previously demonstrated sinusoidal transport abnormalities ethinylestradiol-induced cholestasis is also associated with multiple canalicular membrane transport alterations in rat liver. Hence, functional transport alterations at both polar surface domains might ultimately be responsible for the inhibitory effects of estrogens on the organic anion excretory capacity and on bile formation in rat liver. PMID- 8514880 TI - Early molecular replication of human immunodeficiency virus type 1 in cultured blood-derived T helper dendritic cells. AB - The rate and efficiency of key steps in the life cycle of the human immunodeficiency virus type 1 was examined in three primary cell types, T cells, monocytes, and T helper dendritic cells using the same quantity of virus involved and same cell number. The results show that viral DNA synthesis proceeds much more rapidly and efficiently in primary T helper dendritic cell populations than in primary T cell and monocyte populations. The increased rate of virus DNA synthesis is attributable either to an increase in the efficiency and the rate of uptake of the virus particles by the T helper dendritic cells, as compared with that in other cell types, or to an increased efficiency and rate of viral DNA synthesis in the T helper dendritic cells. In the subsequent phase of viral expression the appearance of spliced viral mRNA products also occur more rapidly in cultures of primary-blood-derived T helper dendritic cells than is the case in primary T cells and monocytes. The increased efficiency of the early steps of HIV 1 replication in primary-blood-derived T helper dendritic cells than in other blood-derived mononuclear cells raises the possibility that these cells play a central role in HIV-1 infection and pathogenesis. PMID- 8514882 TI - Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. AB - Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed. PMID- 8514881 TI - Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross reacting with self antigens. AB - To examine the human antibody repertoire generated against a biologically significant antigen we have obtained sequences of heavy chain variable region genes (IgVH) from 15 monoclonal antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b (Hib PS). All VH segments are members of the VH3 family and 9 of 15 are members of the smaller VH3b subfamily. Restriction is evident by the shared use of certain VDJ joints in independent hybridomas from different subjects. Two hybridomas generated from the same subject demonstrate identical heavy chain variable region gene sequences but differ in isotype and rearrange alternative light chain variable region genes (IgVL), suggesting that in a normal immune response, a single pre-B cell clone may use different light chain rearrangements and give rise to progeny capable of reacting with antigen. Using a polymerase chain reaction assay optimized to detect base pair differences among VH genes we demonstrate that at least a portion of expressed anti-Hib PS VH genes have undergone somatic mutation. Anti Hib PS heavy chain genes are homologous to VH segments encoding autoantibodies and two hybridomas secrete anti-Hib PS antibody that cross-reacts with self antigens (double-stranded DNA and single-stranded DNA). Comparison of VH regions of self-reactive and monospecific anti-Hib PS Ab demonstrates no consistent structural feature correlating with fine antigen specificity. These data demonstrate significant restriction in VH usage and VDJ recombination in the anti Hib PS response and confirm that autoantibodies may be elicited during normal immune responses. PMID- 8514883 TI - Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor. AB - In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-INH was infused before E. coli endotoxin administration. In both groups, endotoxin produced hypodynamic shock; however, the decrease in the systolic index and the ventricular systolic work indexes were greater in controls than the C1-INH group. In controls, the arterial O2 partial pressure decreased by 30% and the alveolo-arterial O2 difference increased by 625%, these parameters remained unchanged in the C1-INH group. Hypoxemia was associated with increased intrapulmonary shunt, decreased blood coagulation contact factors, and decreased C3c. In contrast, C1-INH administration prevented endotoxin-induced hypoxemia, the increase in intrapulmonary shunt, and the decrease in blood coagulation contact factors. This study shows that, in dogs with endotoxic shock, pulmonary dysfunction is associated with an activation of the blood coagulation contact phase system. An inhibition of this system by C1 INH prevented the hypoxemia induced by endotoxic shock. PMID- 8514884 TI - Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. AB - HIV encephalitis is unusual in that neurologic damage occurs in the absence of significant infection of neuronal or glial cells. Because the predominant infected cell in the brain is the macrophage, it has been proposed that release of viral or immune activation factors from macrophages may mediate neurologic damage. Numerous studies have examined the concentration of immune activation factors in the cerebrospinal fluid (CSF), however, there has been no correlation between these CSF measurements and severity of HIV encephalitis (Wiley, C.A., C.L. Achim, R.D. Schrier, M.P. Heyes, J.A. McCutchen, and I. Grant. 1992. AIDS (Phila.). 6:1299-1307. Because CSF measurements may not represent tissue concentrations of these factors, we examined the concentrations of HIV p24, quinolinic acid (QUIN), IL-1, IL-3, IL-6, TNF-alpha, and GMCSF within the brains of 10 AIDS autopsies. Homogenization and extraction of cortical gray, cortical white and deep gray matter showed a good correlation between the amount of HIV gp41 immunostaining and extracted HIV gag protein p24. The concentrations of cytokines were low in the tissue extracts and showed no correlation with severity of HIV encephalitis. Brain extracts from mild cases of HIV encephalitis showed elevated levels of TNF-alpha in deep gray matter, while in more severe cases, elevated TNF-alpha levels were also found within cortical white and cortical gray matter. Brain tissue and CSF QUIN concentrations were substantially increased compared to control values. QUIN concentrations were not correlated with the severity of HIV encephalitis. We conclude that increased tissue levels of TNF alpha and QUIN may have a role in the etiology of HIV-related neurologic dysfunction. PMID- 8514885 TI - Sucrase-alpha-dextrinase in the rat. Postinsertional conversion to inactive molecular species by a carbohydrate-free diet. AB - Absence of dietary carbohydrate decreases both activities of intestinal brush border sucrase-alpha-dextrinase. We examined the molecular mechanism causing this decrease. Adult rats were fed chow (70% CHO) or matched carbohydrate-free (CHO free) diet for 7 d. Sucrase activity decreased by 50% in whole homogenates and brush borders. Enzyme kinetics revealed no change in sucrose affinity (CHO-free Km = 18 mM, chow Km = 21 mM), but fewer active sites (CHO-free Vmax = 2,720, chow Vmax = 5,000 mumol/min per g protein). Intraintestinal pulse-labeling of [35S]methionine in vivo revealed no differences in incorporation into sucrase. Immunoreactive sucrase protein, assayed by ELISA and rocket immunoelectrophoresis, increased twofold per milliunit of sucrase enzymatic activity in CHO-free jejunum. Total immunosucrase (St), the sum of active and inactive enzyme (St = Sa+Si), was unchanged with carbohydrate withdrawal, but > 50% of the sucrase protein became inactive. SDS-PAGE of sucrase immunoprecipitates revealed alteration of alpha, beta, and gamma subunits in CHO free animals: (a) alpha and beta subunits migrated farther (mass change--2 kD); and (b) the alpha subunit became diffuse or was a doublet and was less abundant than the beta subunit. Rather than representing loss of sucrase protein, the decline in sucrase activity is achieved with structural subunit changes, probably involving postinsertional processing. PMID- 8514886 TI - Herbimycin A, a pp60c-src tyrosine kinase inhibitor, inhibits osteoclastic bone resorption in vitro and hypercalcemia in vivo. AB - Since absence of expression of the c-src gene product in mice indicates that the pp60c-src tyrosine kinase is required and essential for osteoclastic bone resorption, we tested the effects of the antibiotic herbimycin A, which is an inhibitor of pp60c-src on osteoclastic bone resorption in vitro and on hypercalcemia in vivo. We examined the effects of herbimycin A on the formation of bone resorbing osteoclasts in mouse long-term marrow cultures, on isolated rodent osteoclasts and on bone resorption in organ cultures of fetal rat long bones stimulated by parathyroid hormone. We found that herbimycin A in concentrations of 1-100 ng/ml inhibited bone resorption in each of these systems. We determined the effects of herbimycin A (100 ng/ml) on src tyrosine kinase activity in mouse marrow cultures and found that it was decreased. Herbimycin A also decreased elevated blood calcium levels that were induced either by repeated subcutaneous injections of recombinant human interleukin-1 alpha or by a human tumor. There was no evidence for toxicity in any of these culture systems or in mice treated with herbimycin A. A different tyrosine kinase inhibitor that does not inhibit pp60c-src was used as a control and caused none of these effects. These data suggest that pp60c-src tyrosine kinase inhibitors may be useful pharmacologic inhibitors of osteoclastic bone resorption and hypercalcemia. PMID- 8514887 TI - Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo. AB - We studied the influence of glucagon on hepatic LDL receptors and plasma lipoproteins in rats. A dose-dependent (maximum, threefold) increase in LDL receptor binding was evident already at a dose of 2 x 4 micrograms, and detectable 3 h after injection; concomitantly, cholesterol and apolipoprotein (apo) B and apoE within LDL and large HDL decreased in plasma. LDL receptor mRNA levels were however unaltered or reduced. Hepatic microsomal cholesterol was increased and the enzymatic activities of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in hepatic microsomes were reduced. Insulin alone increased receptor binding and receptor mRNA levels twofold, but plasma cholesterol was unchanged and plasma apoE and apoB increased. Administration of insulin to glucagon-treated animals reduced the LDL-receptor binding to control levels and apoB appeared in LDL particles. Estrogen treatment increased LDL-receptor binding and mRNA levels five- and eightfold, respectively. Combined treatment with glucagon and estrogen reduced the stimulation of LDL receptor mRNA levels by 80% although LDL-receptor binding was unchanged. Immunoblot analysis showed that glucagon increased the number of hepatic LDL receptors. We conclude that glucagon induces the number of hepatic LDL receptors by a mechanism not related to increased mRNA levels, suggesting the presence of a posttranscriptional regulatory mechanism present in the liver in vivo. PMID- 8514888 TI - Interleukin-6 production in posttransplant lymphoproliferative disease. AB - IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25 x 10(6) IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD. PMID- 8514889 TI - Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations. AB - The molecular pathology of somatotrophinomas has been investigated by a combined search for dominant mutations of the gene encoding the Gs alpha protein and for recessive mutations involving chromosome 11q13, which contains the gene causing multiple endocrine neoplasia type 1 (MEN1). Somatotrophinomas and peripheral leukocytes were obtained from thirteen patients with acromegaly; one patient also suffered from MEN1. Five DNA probes identifying restriction fragment length polymorphisms from 11q revealed allele loss in pituitary tumors from five (four non-MEN1 and one MEN1) patients. Deletion mapping revealed that the region of allele loss common to the somatotrophinomas involved 11q13. An analysis for similar allelic deletions at 12 other loci from chromosomes 1-5, 7-9, 12-14, and 17 did not reveal generalized allele loss in the somatotrophinomas. These results, which represent the first report of chromosome 11 allele loss occurring in non-MEN1 somatotrophinomas, indicate that a recessive oncogene on 11q13 is specifically involved in the monoclonal development of somatotrophinomas. In addition Gs alpha mutations were detected in two non-MEN1 somatotrophinomas, one of which also revealed allele loss of chromosome 11. Thus, our results reveal that the development of somatotrophinomas is associated with alterations in both dominant and recessive oncogenes and further characterization of these genetic abnormalities will help to elucidate the multistep etiology and progression of somatotrophinomas. PMID- 8514890 TI - Reversible inhibition of urea exchange in rat hepatocytes. AB - Urea exchange is enhanced in renal collecting duct cells and erythrocytes by transporters which can be inhibited by phloretin and urea analogs such as thiourea. In this study, evidence for a comparable transporter was found in rat livers perfused with solutions which contained no red cells and in suspensions of hepatocytes. Bolus injections containing 125I-albumin (intravascular indicator), 99mTc-DTPA (extracellular indicator), 3HOH (water indicator), and [14C]urea were administered into the portal vein and fluid was collected from the hepatic vein. Under control conditions, [14C]urea and 3HOH emerged from the hepatic vein at nearly the same rate. However when the perfusate contained 2.5 mM phloretin (equivalent to 0.058 mM phloretin not bound to albumin), the amount of [14C]urea which had been recovered in the hepatic venous outflow by the time of peak 125I albumin concentrations exceeded 3HOH recovery by a factor of 2.31 +/- 0.23 (n = 7). When the perfusate contained 200 mM thiourea, the comparable recovery of [14C]urea from the hepatic veins exceeded that of 3HOH by a factor of 3.48 +/- 0.44 (n = 7). These effects were at least partially reversible and suggested inhibition of urea transporters in hepatocytes. This conclusion was supported by studies of unloading of [14C]urea from hepatocytes which were exposed to unlabeled solutions: in the presence of phloretin, the amount of [14C]urea remaining within hepatocytes at 4 s was approximately twice that remaining in hepatocytes which had not been exposed to phloretin. Rapid transport of urea out of hepatocytes may increase urea synthesis and minimize cellular swelling due to urea accumulation. PMID- 8514891 TI - Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages. AB - The development of antigen-specific functional T lymphocyte immunity in infants and children is an area of immunology that needs elucidation. Leukocytes from cord blood (CBL) and from PBL of children of different ages who were in the hospital for minor surgical procedures were compared with PBL from healthy adults for their ability to generate T helper cell (Th) responses assessed by in vitro proliferation and IL-2 production after stimulation with: influenza A virus (FLU); tetanus toxoid (TET); adult allogeneic PBL that were either undepleted (ALLO) or depleted of adherent antigen presenting cells (ALLONW); and PHA. CBL generated Th responses to ALLONW, ALLO, and PHA, but not to FLU or TET. PBL from infants between 6 and 13 mo of age responded to ALLO and PHA; none responded to FLU or ALLONW, and two of four responded weakly to TET. PBL from children between 13 and 26 mo of age responded to all stimuli except FLU, to which only one child responded marginally. PBL from children older than 36 mo responded to all stimuli at levels comparable to those of PBL from adults. The use of undepleted and adherent cell-depleted CBL and PBL from children of different ages as allogeneic stimulators of responses generated by PBL from adults indicated that the antigen presenting function of CBL and PBL from children 13 mo or older are sufficiently developed to present alloantigen, whereas PBL from children younger than 13 mo are not. Therefore, our results indicate that age-dependent differences exist in both T helper and antigen-presenting functions of CBL and PBL from children of different ages. Surprisingly, CBL appear to be more efficient in antigen presenting function than PBL from children younger than 13 mo. These findings are important for establishing developmental parameters of T helper cell immunity relevant for pediatric infection and transplantation in infants and children. PMID- 8514892 TI - Hormonal control of intestinal Fc receptor gene expression and immunoglobulin transport in suckling rats. AB - Hormonal control of immunoglobulin (Ig) absorption and of intestinal Fc receptor mRNA expression were investigated in rats to assess its potential role in the normal postsuckling inhibition of this transport system. Corticosterone and L thyroxine therapy caused premature inhibition of the absorption of orally administered murine monoclonal antibody and of Fc receptor mRNA expression in a dose- and time-dependent manner. Low-dose corticosterone had no effect on Fc receptor mRNA synthesis after 3 d but decreased Ig transport fivefold after 7 d. High dose corticosterone resulted in a threefold reduction in Fc receptor after 3 d, and there was almost complete inhibition (> 30-fold) of transport and of Fc receptor transcript levels after 7 d. Similarly, 7 d of high-dose thyroxine decreased both serum Ig transport and Fc receptor (> 30-fold). However, adrenalectomy did not prevent the normal post-suckling declines in Ig transport or receptor synthesis. This study demonstrates that exogenous corticosteroids and thyroxine hormone inhibit Ig transport and steady-state duodenal Fc receptor mRNA levels in suckling rats. Endogenous adrenal steroids however, do not appear to be entirely responsible for the age-dependent decline in this transport system. PMID- 8514893 TI - Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. AB - This study was designed to test the hypothesis that tissue factor pathway inhibitor (TFPI) plays a significant role in vivo in regulating coagulation that results from exposure of blood to tissue factor after vascular injury as in the case of gram negative sepsis. Highly purified recombinant TFPI (6 mg/kg) was administered either 30 min or 4 h after the start of a lethal intravenous Escherichia coli infusion in baboons. Early posttreatment of TFPI resulted in (a) permanent seven-day survivors (5/5) with significant improvement in quality of life, while the mean survival time for the controls (5/5) was 39.9 h (no survivors); and (b) significant attenuations of the coagulation response and various measures of cell injury, with significant reductions in pathology observed in E. coli sepsis target organs, including kidneys, adrenals, and lungs. TFPI administration did not affect the reduction in mean systemic arterial pressure, the increases in respiration and heart rate, or temperature changes associated with the bacterial infusion. TFPI treated E. coli infected baboons had significantly lower IL-6 levels than their phosphate buffered saline-treated controls, however tumor necrosis factor levels were similarly elevated in both groups. In contrast to the earlier 30-min treatment, the administration of TFPI at 4 h, i.e., 240 min, after the start of bacterial infusion resulted in prolongation of survival time, with 40% survival rate (2/5) and some attenuation of the coagulopathic response, especially in animals in which fibrinogen levels were above 10% of normal at the time of TFPI administration. Results provide evidence for the significance of tissue factor and tissue factor pathway inhibitor in bacterial sepsis, and suggest a role for blood coagulation in the regulation of the inflammatory response. PMID- 8514894 TI - Skeletal muscle expression and abnormal function of beta-myosin in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy is an important inherited disease. The phenotype has been linked, in some kindreds, to the beta-myosin heavy chain (beta-MHC) gene. Missense and silent mutations in the beta-MHC gene were used as markers to demonstrate the expression of mutant and normal cardiac beta-MHC gene message in skeletal muscle of hypertrophic cardiomyopathy patients. Mutant beta-myosin, also shown to be present in skeletal muscle by Western blot analysis, translocated actin filaments slower than normal controls in an in vitro motility assay. Thus, single amino acid changes in beta-myosin result in abnormal actomyosin interactions, confirming the primary role of missense mutations in beta-MHC gene in the etiology of hypertrophic cardiomyopathy. PMID- 8514896 TI - Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: a longitudinal study. AB - Ultrasonography of prospectively followed chronic hepatitis B patients who developed liver cirrhosis were reevaluated in order to identify the ultrasonographic changes of early cirrhosis. Ultrasonographic features of 29 patients before and after cirrhosis were as follows: portal vein diameter--1.20 cm/1.29 cm (NS); cirrhosis score--5.69/7.52 (p < 0.01); spleen size index--21.99 cm2/25.84 cm2 (NS). The result suggests that ultrasonographic diagnosis of early cirrhosis is not easy on a single occasion; however, the score system method is helpful in longitudinal follow-up chronic hepatitis patients. A careful comparison of hepatic parenchymal and surface changes are mandatory. PMID- 8514895 TI - Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection. AB - Polymyositis is an inflammatory myopathy characterized by mononuclear cell infiltration of muscle tissue. Myocytotoxic T lymphocytes have been recognized in the infiltrates, but the muscle antigen, target of the immune attack, has not been identified. Molecular characterization of the variable regions of T cell receptors (TCRs) on the infiltrating lymphocytes can be expected to provide insights into the pathogenic process. The V alpha/beta TCR repertoire was investigated by RNA-PCR in muscle biopsies from 15 polymyositis patients and 16 controls (6 Duchenne muscular dystrophy and 10 with no inflammatory or dystrophic myopathy). A variety of rearranged variable TCR genes was found in polymyositis, V alpha 1, V alpha 5, V beta 1, and V beta 15 being the most common (present in 60-100% of patients). In Duchenne muscular dystrophy patients TCR V alpha or beta rearrangements were found although no restriction was observed; no rearrangements were found in muscles from the other controls. Sequence analysis revealed the presence of the J beta 2.1 region in 90% of the V beta 15 clones studied, no random N additions in the diversity region, and a common motif within the CDR3 region. These results suggest that selection of muscle-infiltrating T lymphocytes is antigen driven in polymyositis. PMID- 8514897 TI - Sonographic features of retroperitoneal neurilemoma. AB - Seven cases of retroperitoneal neurilemoma confirmed by histology had an ultrasound examination. There were 5 women and 2 men with a mean age of 55. Most of the cases (5/7) had a palpable mass clinically. Of the 7 cases, 4 had a mass with cystic degeneration and internal echoes on sonogram, consistent with the macroscopic findings of tumors. The internal echoes represented blood clots and residual tissue (or septa) in cyst. Of the remaining 3 cases, one showed a confluent lobulated mass, the second had a solitary homogeneous mass with small cysts, and the third one, which was the smallest (4 cm x 4 cm x 6 cm), had a hypoechoic and homogeneous pattern. The sonograms of all 7 cases were consistent with the macroscopic features of the tumors. The sonographic pattern of tumor parenchyma is either homogenously hyperechoic or hypoechoic. Because of the cystic degeneration, hemorrhage, and residual tissue of retroperitoneal neurilemoma, the sonographic pattern was variable. PMID- 8514898 TI - Visualization of implantable defibrillator patches by two-dimensional echocardiography. AB - Implantable cardioverter defibrillators are being used with increasing frequency for the management of life-threatening ventricular arrhythmias. In order to determine whether the titanium mesh of the defibrillator patch causes ultrasonographic acoustical interference, 30 patients underwent prospective serial echocardiographic examination. In addition, studies were reviewed to determine whether the defibrillator patches could be visualized with standard two dimensional echocardiography. In no patient did the anterior patch produce acoustical interference, and, unless specific measures were utilized (such as a standoff pad, a zoom feature, or a 5-MHz transducer), the patches were rarely visualized. PMID- 8514899 TI - Reference values for Doppler velocimetric indices from the fetal and placental ends of the umbilical artery during normal pregnancy. AB - A range-gated Doppler ultrasound system combined with a real-time imaging system was used to determine arterial blood velocity values from the fetal and placental ends of the umbilical cord in 269 normal pregnancies between 17 and 40 weeks, menstrual age. The systolic-diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) were higher at the fetal end compared to the placental end of the cord. The individual differences in these Doppler indices, obtained between the fetal and placental recording sites, were inversely related to menstrual age: S/D: r = -0.38, p < 0.001; PI: r = -0.25, p < 0.001; and RI: r = 0.15, p < 0.01. After normalization for the angle of insonation, the peak systolic velocity was higher and the end-diastolic velocity was lower at the fetal than at the placental end of the cord. It is concluded that routine recordings for Doppler velocimetric indices should take into account the recording site on the umbilical cord in order to reduce methodological sources of variance, especially during midgestation. Furthermore, the data presented here in the form of the median and percentile values are proposed as normal reference values to facilitate this procedure. PMID- 8514900 TI - Chronic liver disease: comparison of ultrasound patterns with laparoscopy and biopsy. AB - We studied the correlation of ultrasound patterns with laparoscopy and biopsy results in 140 patients with chronic liver disease (CLD). Of the 23 patients with a normal ultrasound pattern (N), biopsies revealed CLD in 18; in the 22 patients with unspecified hepatomegaly (H), biopsies disclosed CLD in 20; and in the 64 patients with a homogeneous bright pattern (HB), biopsies showed CLD in 62. All 22 cases of heterogeneous bright pattern (HTB) and all 9 patients with nodular pattern (ND) had CLD. In conclusion, it appears that the HTB and nodular ultrasound patterns confirm the presence of CLD, the HB pattern is suggestive of CLD, but diagnosis of CLD cannot be made from N and H patterns. PMID- 8514901 TI - Sonographic detection of hepatic portal venous gas associated with suppurative cholangitis. PMID- 8514902 TI - Cloacal exstrophy in monozygotic twins detected through antenatal ultrasound scanning. PMID- 8514903 TI - Gallstone ileus treated with extracorporeal shock wave lithotripsy. PMID- 8514904 TI - Meconium peritonitis: a new finding in rubella syndrome. PMID- 8514905 TI - Ultrasound-guided fine-needle aspiration of a nasopharyngeal mass. PMID- 8514906 TI - Factors affecting the utilization of prenatal health care services in Jerusalem. AB - Health service utilization patterns during pregnancy were studied among 780 women from selected neighborhoods of Jerusalem who delivered between December 1, 1985 and June 30, 1986. Factors affecting the choice of care-provider, the timing of the first contact with the prenatal care service and the frequency of visits to prenatal care centers were studied with respect to several demographic, socio economic and needs variables. About one half of the women visited the Family Health Centers, the traditional site for delivery of prenatal care. Forty percent visited their regular doctor during pregnancy while about 30% sought private care. In all, fifty two percent of women consulted more than one source of medical care service during pregnancy. Logistic regression analysis showed that the choice of care was determined by the type of insurance, need factors and education. The timing of the first visit depended on origin, level of education and parity. The frequency of visits was related to the type of insurance and to perceived health. PMID- 8514907 TI - An epidemiologic study of primary health care service utilization of summer visitors to Abha, Asir, Saudi Arabia. AB - Primary health care (PHC) service utilization by summer visitors to Abha, Saudi Arabia was studied among 227 families including 1443 persons attending the Al Manhal Primary Health Care Center (PHCC) during August 1991. Summer visitors added an excess load on PHC services: 1.8% for preventive activities, 3.3% for diagnostic activities and 17.4% for curative activities. A significant excess of utilization of curative PHC activities was observed among summer visitors compared to residents. On the other hand, a significant decrease in utilization of preventive and diagnostic PHC services was noted among summer visitors. This study demonstrates the importance of augmenting PHCCs with staff and supplies in residential areas during the summer to cope with the situation and of providing proper and adequate PHC services. More health education is needed to inform people about importance of preventive PHC for better utilization of the available services. PMID- 8514908 TI - Project CONNECT: an interagency partnership to confront new challenges facing at risk women and children in New York City. AB - Project CONNECT is a New York State--New York City collaborative venture to facilitate access to, coordinate and expand the delivery of health and human services, during the perinatal period to women and children in the three areas of New York City with the highest rates of morbidity and mortality. Based on the concept of comprehensive case management, CONNECT coordinates diverse providers around existing resources. Services implemented by community-based case managers for families in need include: medical care, substance/alcohol abuse treatment, foster care preventive services, parent education, developmental assessment, screening and child care. The initial points of entry to CONNECT are specific hospitals within the three targeted neighborhoods. Additional points of entry, including other hospitals and prenatal care sites, are being added on an incremental basis. Enrollment in CONNECT is also enrollment in Medicaid and participants are eligible for Medicaid services. It is expected that the CONNECT program will result in improved birth and health outcomes for women and their children, reduction in chemical dependency and improved family preservation. The state and city agencies that created CONNECT hope that by working together, through a very specific interagency agreement monitored by the offices of the Governor and the Mayor, they will be able to reach those families who have many needs, but traditionally have been difficult to engage and keep involved in the service delivery system. The ultimate benefit will go to the family as a whole, particularly the children, both the newborns and their siblings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514909 TI - Effectiveness of family notification efforts and compliance with measles post exposure prophylaxis. AB - Exposures to measles in medical settings have contributed to the recent resurgence of the disease in the United States. Following a measles exposure in two pediatric medical facilities serving an inner-city population, we investigated the effectiveness of a disease notification strategy and compliance of the exposed population with recommendations for post-exposure prophylaxis, two requirements of a successful intervention program. Of 106 families with children eligible for a prophylactic vaccination by standard guidelines, 64% were notified of exposure by telephone. Compliance was assessed by a brief telephone questionnaire based upon the Health Belief Model, and verified by medical records. Forty-six families were interviewed regarding their decisions to comply with the recommendations. Most (75%) families were compliant. Compliant parents perceived measles to be severe and their children to be in excellent health. In a multiple logistic regression analysis, only the perceived severity of measles significantly contributed to the model. We conclude that: infection control outreach may need to extend beyond telephone notification for an inner-city population, and that once notified, most people will comply with recommendations. The Health Belief Model explains compliance with infection control measures and may be useful in guiding public health interventions. PMID- 8514910 TI - The effect of coordinated, multidisciplinary ambulatory care on service use, charges, quality of care and patient satisfaction in the elderly. AB - This study evaluated a multidisciplinary care center, the Pike Market Clinic (PMC), whose physicians provide and coordinate inpatient and outpatient care for downtown low-income elderly in Seattle. We interviewed users of PMC and their near-neighbors with a 206 item questionnaire to compare their medical and social service use, quality of care, and satisfaction. We then estimated mean annual charges/person for inpatient, outpatient and emergency room services in the two groups. Demographic and health status characteristics were similar in the two groups. PMC patients made significantly more annual visits than neighbors to their primary physicians. Visits to non-primary physicians occurred at the same rate in both groups, but PMC patients were referred more often by their primary physicians. Both emergency room and inpatient use were higher in the neighbor group. Social services were used at the same rate by PMC patients and neighbors. Various indices suggested that quality of care and satisfaction were comparable or superior among PMC patients. Using utilization data, we estimated that neighbors generated charges over $1000/person/year greater than PMC patients. Coordination by PMC providers rather than the availability of multidisciplinary services may be largely responsible for utilization differences between PMC patients and their neighbors. PMID- 8514911 TI - Midbrain dopaminergic neurons (nuclei A8, A9, and A10): three-dimensional reconstruction in the rat. AB - The dopaminergic neurons in the midbrain of the rat are located in three cell groups: nucleus A8 cells in the retrorubral field, nucleus A9 cells in the substantia nigra, and nucleus A10 cells in the ventral tegmental area and related nuclei. The purpose of the present study was to map and quantify the midbrain dopaminergic neurons in two and three dimensions in the rat brain, using immunohistochemical staining and computer imaging techniques. The cells were identified with an antibody against tyrosine hydroxylase, and counted in six midbrain nuclei: the retrorubral field, substantia nigra pars compacta, substantia nigra pars reticulata, central linear nucleus, ventral tegmental area, and interfascicular nucleus. Outlines were traced around the perimeters of the coronal tissue sections, and the locations of all immunoreactive ventral midbrain cells were mapped. On one side of the brain there are approximately 1,300 nucleus A8 cells, 10,500 nucleus A9 cells, and 10,200 nucleus A10 cells. The 2- and 3 dimensional reconstructions illustrate the region-specific density of dopaminergic neurons throughout the midbrain cell complex, and provide a visual appreciation of the location and distribution of the three dopaminergic cell groups in relation to their position in the midbrain. Information about the number and location of midbrain dopaminergic neurons will be useful in conjunction with future studies that characterize these cells more specifically, for example, in terms of their co-transmitters, and afferent and efferent projections. PMID- 8514912 TI - Medial cortex of the lizard Gekko gecko: a hodological study with emphasis on regional specialization. AB - There is increasing evidence that the archicortex in mammals and reptiles is not a homogeneous structure. However, little is known about the regional specialization of this cortical area in reptiles. Therefore, the efferent connections of the medial cortex of the lizard Gekko gecko were studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin. The small-celled part of the medial cortex (Cxms) projects to various parts of the septum in a topological way: the rostral part projects to the anterior septal nucleus, whereas the caudal part projects to the lateral septal nucleus and the nucleus septi impar. In addition, Cxms projects to the large-celled part of the medial cortex (Cxml). Axons that originate from the dorsal part of Cxms terminate at the proximal parts of the apical and basal dendrites of the neurons of Cxml caudal to the injection site. In contrast, fibers originating from the ventral part terminate on more distal parts of the dendrites of neurons of Cxml rostral to the injection site. Other projections from Cxms to the dorsal cortex (Cxd) and the external amygdaloid nucleus were found. The Cxml projects bilaterally to Cxms. These projections terminate in the superficial and deep plexiform layers. In addition, projections to the cell plate of Unger, Cxd, and to the lateral septal nucleus were found. It appears, on the basis of the efferent connections, that Cxms can be divided into a rostral and caudal part, while hodological differences also exist between the dorsal and ventral parts of Cxms. The results of the present study do not suggest a subdivision of Cxml. The regional variations of the medial cortex in the lizard Gekko gecko differ from the regional variations described in other reptilian species. PMID- 8514913 TI - Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. AB - Nonradioactive in situ hybridization methods with digoxigenin-labeled cRNA probes were used to localize two glutamic acid decarboxylase (GAD) mRNAs in rat brain. These mRNAs encode two forms of GAD that both synthesize GABA but differ in a number of characteristics including their molecular size (65 and 67 kDa). For each GAD mRNA, discrete neuronal labeling with high cellular resolution and low background staining was obtained in most populations of known GABA neurons. In addition, the current methods revealed differences in the intensity of labeling among neurons for each GAD mRNA, suggesting that the relative concentrations of each GAD mRNA may be higher in some groups of GABA neurons than in others. Most major classes of GABA neurons were labeled for each GAD mRNA. In some groups of GABA neurons, the labeling for the two mRNAs was virtually identical, as in the reticular nucleus of the thalamus. In other groups of neurons, although there was substantial labeling for each GAD mRNA, labeling for one of the mRNAs was noticeably stronger than for the other. In most brain regions, such as the cerebellar cortex, labeling for GAD67 mRNA was stronger than for GAD65 mRNA, but there were a few brain regions in which labeling for GAD65 mRNA was more pronounced, and these included some regions of the hypothalamus. Finally, some groups of GABA neurons were predominantly labeled for one of the GAD mRNAs and showed little or no detectable labeling for the other GAD mRNA, as, for example, in neurons of the tuberomammillary nucleus of the hypothalamus where labeling for GAD67 mRNA was very strong but no labeling for GAD65 mRNA was evident. The findings suggest that most classes of GABA neurons in the central nervous system (CNS) contain mRNAs for at least two forms of GAD, and thus, have dual enzyme systems for the synthesis of GABA. Higher levels of one or the other GAD mRNA in certain groups of GABA neurons may be related to differences in the functional properties of these neurons and their means of regulating GABA synthesis. PMID- 8514914 TI - Noradrenaline in the brain of the South African clawed frog Xenopus laevis: a study with antibodies against noradrenaline and dopamine-beta-hydroxylase. AB - To obtain insight into the noradrenergic system of amphibians, the distribution of noradrenaline was studied immunohistochemically with antibodies against noradrenaline (NA) and dopamine-beta-hydroxylase (DBH) in the brain of the South African clawed frog Xenopus laevis. Noradrenaline-containing cell bodies are found in the hypothalamic periventricular organ, the isthmic region, and in an area ventral and medial to the solitary tract. Noradrenaline-immunoreactive (NAi) fibers are widely, but not uniformly, distributed throughout the brain and spinal cord. In the telencephalon, dense plexuses of NAi fibers are present dorsomedial to the nucleus accumbens, in the nucleus of the diagonal band, the dorsolateral part of the striatum, the medial amygdala, and in an area that encompasses the lateral forebrain bundle. In the diencephalon, dense plexuses are found ventrolateral to the periventricular organ, in the posterior tubercle, and in the intermediate lobe of the hypophysis. Compared to the forebrain, the brainstem and spinal cord are less densely innervated by NAi fibers. The distribution of DBHi cell bodies and fibers resembles the pattern revealed with the NA antibodies. An exception is formed by the liquor contacting cells of the hypothalamic periventricular organ, which are immunonegative for the DBH antiserum. It is suggested that these cells accumulate rather than metabolize catecholamines. The present study combined with the results of a previous report in Xenopus on the distribution of dopamine (Gonzalez, Tuinhof, Smeets, '93, Anat. Embryol. 187:193 201) offers the opportunity to differentiate between the two catecholamines. For example, it is now shown that both dopaminergic and noradrenergic fibers innervate the intermediate lobe of the hypophysis and that, therefore, both catecholamines are likely involved in background adaptation. PMID- 8514916 TI - Quantitative autoradiography of somatostatin receptors in the rat limbic system. AB - The distribution of somatostatin receptors (SRIF-R) was analyzed in the limbic system of the adult rat by in vitro autoradiography with [125I-Tyr0,DTrp 8]S14 as a radioligand. Precise quantification of the density of binding sites, at 0.2 mm intervals throughout the different areas revealed a marked heterogeneity of labeling in most structures. In particular, SRIF-R were concentrated in the basal (104.4 +/- 3.3 fmol/mg proteins) and basolateral amygdaloid nuclei (94.8 +/- 4.3 fmol/mg proteins), and in the nucleus of the lateral olfactory tract (121.6 +/- 2.4 fmol/mg proteins), whereas moderate densities were detected in the amygdalo hippocampal nucleus (76.4 +/- 2.8 fmol/mg proteins). The medial (41.3 +/- 1.9 fmol/mg proteins) and the central (24.0 +/- 1.4 fmol/mg proteins) amygdaloid nuclei contained lower SRIF-R concentrations. It appears from these observations, in the light of the anatomical pathways of the amygdala, that intra-amygdalian SRIF-containing neurons project to the amygdalo-hippocampal nucleus, and that SRIF-R in the basolateral complex are the target of afferents from limbic cortical areas. SRIF-R were detected at different levels of the hippocampal formation but their distribution was more restricted than that of SRIF-containing fibers. The maximal density of sites was detected in the ventral and dorsal parts of the subiculum (115.0 +/- 3.4 and 87.0 +/- 2.8 fmol/mg proteins, respectively) and in the parasubiculum (100.1 +/- 5.4 fmol/mg proteins). In Ammon's horn, the stratum oriens and stratum radiatum of the CA1 field were the only sites enriched in SRIF-R (74.1 +/- 2.0 and 74.6 +/- 1.9 fmol/mg proteins, respectively). The apparent lack of receptors in the pyramidal cell layer indicated that, in Ammon's horn, SRIF is involved in intra-hippocampal communication. Low levels of receptors were found in the hippocampal CA2 and CA3 fields. SRIF-R in the dentate gyrus were mainly concentrated in the molecular layer (57.3 +/- 1.2 fmol/mg proteins). A very high density of sites was also observed in the entorhinal cortex (up to 123.1 +/- 1.5 fmol/mg proteins). A clear mismatch between SRIF and SRIF-R was detected in the septum and the habenula. In the profound layers of the cingulum and retrosplenial cortex, a heterogeneous distribution of SRIF-R was observed. High concentrations of sites were detected in the rostral zone of the cingulate cortex (93.4 +/- 2.0 fmol/mg proteins) while the posterior cingulate only exhibited moderate concentrations of sites (66.5 +/- 0.7 fmol/mg proteins).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8514915 TI - Protein kinase C-delta in rat brain: association with sensory neuronal hierarchies. AB - Originally characterized as the calcium- and phospholipid-dependent protein kinases, the protein kinases C include at least eight separate isoforms, some of which are calcium-independent and all of which are highly enriched in brain. Of the calcium-independent isoforms, the delta subspecies of protein kinase C has the most restricted complement of lipid activators and substrate specificity, suggesting that it may have a unique role in cell signalling pathways. Using immunocytochemistry, we report that the distribution of protein kinase C-delta immunoreactivity in rat brain is also restricted, being present in all sensory systems. Moreover, it is found in alternating hierarchies of sensory pathways: in all sensory systems except auditory, it is found in first- and third-order neurons, while in the auditory system, it is found in second- and fourth-order neurons. Thalamocortical systems are intensely immunoreactive, including barrel fields of the rat parietal cortex. Outside of sensory systems, protein kinase C delta is present in cerebellum within longitudinal stripes in Purkinje neurons, and in the caudate-putamen, it appears to be associated with the striosome (patch) compartment. In contrast to all other protein kinase C isoforms, protein kinase C-delta is absent from hippocampus. These findings suggest that protein kinase C-delta may have a unique role in signal transduction in the central nervous system (CNS), especially in sensory systems. PMID- 8514917 TI - Quantitative phylogenetic constancy of cerebellar Purkinje cell morphological complexity. AB - Golgi-stained material of cerebellar cortices from 17 species was examined by measuring the fractal dimensions of the borders of Purkinje cells, which is a quantitative, objective measure of morphological complexity. Nine species (from birds to man) were chosen for a comparison with ANOVA and no statistically significant differences were found in their fractal dimensions. In contrast, a wide range of differences was found in the membrane areas across species lines. The Sholl coefficient, a measure of branch formation and termination away from the soma, showed no consistent pattern for each cell. We interpret our results as indicating a constancy in morphological cellular complexity of Purkinje cells during late evolutionary time. PMID- 8514918 TI - Spinal and facial innervation of the skin in the gadid fish Ciliata mustela (Teleostei). AB - The pattern of innervation of the skin of the rockling Ciliata mustela was investigated to sort out spinal from facial nerve innervation of cutaneous chemosensory and mechanosensory systems. This fish has a variety of appendages with different functional sensory specializations, i.e., the chin barbel, pelvic fin, anterior dorsal fin, and dorsal trunk skin. The carbocyanine dye, diI, was applied to nerve stumps in dissected aldehyde-fixed tissue. In the case of the chin barbel, the dye was applied to both the trigeminal and facial nerve components. In the other cases, the dye was applied either selectively to the spinal nerves, to the facial nerves, or to both components. In the chin barbel, diI labeled nerve fibers associated with taste buds (TBs) and solitary chemosensory cells (SCCs) as well as relatively blunt free nerve endings, which closely approach the epidermal surface. In the pelvic fin, anterior dorsal fin, and dorsal trunk skin, taste buds, solitary chemosensory cells, and their innervation were labeled only after diI was applied to the facial nerve stumps. Application of diI to spinal nerves labeled delicate, free nerve endings and nerve fibers associated with small cells deep in the epidermis with features characteristic of Merkel cells. Transmission electron microscopy supports these results; after denervation of the facial component of the anterior dorsal fin, synaptic contacts with Merkel cells remained intact, whereas the synapses with the SCCs vanished. PMID- 8514919 TI - Degenerate hearing and sound localization in naked mole rats (Heterocephalus glaber), with an overview of central auditory structures. AB - Behavioral tests of absolute sensitivity and sound localization in African naked mole rats show that, despite their communal social structure and large vocal repertoire, their hearing has degenerated much like that of other subterranean species. First, their ability to detect sound is limited, with their maximum sensitivity being only 35 dB (occurring at 4 kHz). Second, their high-frequency hearing is severely limited, with their hearing range (at 60 dB sound pressure level [SPL]) extending from 65 Hz to only 12.8 kHz. Third, determination of the effect of duration on noise thresholds indicates that, compared with other animals, mole rats require a sound to be present for a much longer duration before reaching asymptotic threshold. Finally, they are unable consistently to localize sounds shorter than 400 ms and cannot accurately localize sounds of longer duration, raising the possibility that they are unable to use binaural locus cues. Thus, it seems that the essentially one-dimensional burrow system of a subterranean habitat produces severe changes in hearing comparable to the changes in vision that result from the absence of light. To explore the relation between vision and sound-localization acuity, retinal ganglion cell densities were determined. The results indicate that naked mole rats have a broad area of best (albeit poor) vision, with maximum acuity estimated at 44 cycles/degree. That mammals with wide fields of best vision have poorer sound-localization acuity than those with narrower fields is consistent with the thesis that a major function of sound localization is to direct the gaze to the source of a sound. However, the fact that subterranean mammals have little use for vision in a lightless environment suggests that they represent an extreme case in this relationship and may explain the fact that, unlike surface-dwelling mammals, they have virtually lost the ability to localize brief sounds. Finally, despite their very limited auditory abilities, the major brainstem auditory nuclei, although relatively small, appear to be present. PMID- 8514920 TI - The octavolateral systems in the stingray, Dasyatis sabina. I. Primary projections of the octaval and lateral line nerves. AB - The central projections of the electrosensory, mechanosensory, and octaval nerves of the Atlantic stingray were examined by transganglionic transport of horseradish peroxidase. Particular attention was paid to the relation of the projections to cell plates C1 and C2, and to a newly described cell plate, C3. The electroreceptors in the stingray are found in three groups on the dorsal and ventral sides of the body. The electroreceptors are represented topographically on the ipsilateral dorsal nucleus. Those of the rostral part of the head and pectoral fins are represented on the rostroventral part of the nucleus, and those on the caudal part of the head and the pectoral fin on the dorsocaudal part of the nucleus. Mechanosensory lateral line afferents terminate within the ipsilateral intermediate and caudal nuclei, and the lateral granular mass of the vestibulocerebellum. Anterior lateral line afferents also project to the magnocellular octaval nucleus. A topographic representation of the mechanosensory lateral line periphery is present on the intermediate and caudal nuclei. Mechanoreceptors on the trunk are represented laterally and those on the head medially. The terminal field of the anterior lateral line afferents on the intermediate nucleus surrounds cell plates C1 and C2. The anterior lateral line afferents also project to the medial part of the lateral granular mass, whereas the posterior lateral line afferents project to the lateral portion. Sparse projections of anterior lateral line afferents to the periventricular octaval nucleus were also observed. The octaval nerve afferents terminate largely within the octaval column. Octaval nerve projections were also observed to the reticular formation, the periventricular octaval nucleus, the deep cerebellar nucleus, the vestibulocerebellum, particularly the lower lip and medial granular mass, and the intermediate nucleus. A sparse projection to cell plate C3 was found. The relation between cell plates C1 and C2 and the anterior lateral line afferents suggests that these cell plates are related to processing lateral line information. While the relationship between cell plate C3 and the octaval afferents is not strong, the sparse octaval projection C3 receives suggests that it is relaying octaval information. PMID- 8514921 TI - GABA- and glycine-immunoreactive neurons in the spinal cord of the carp, Cyprinus carpio. AB - gamma-Aminobutyric acid (GABA) and glycine are the two main inhibitory transmitter amino acids in the central nervous system of vertebrates. The distribution of cells containing GABA and glycine in the carp spinal cord was examined by using specific antisera raised against the two amino acids conjugated to bovine serum albumin. The immunoreaction on serial paraffin sections was visualized by a streptavidin-biotin method. Both antisera gave highly specific labelings of cells. At least three types of GABA-immunoreactive cells were found. They were small cells in the dorsal grey matter, various sized cells in the central and ventral grey, and some ependymal cells contacting the central canal. In addition, very small cells and neuropil structures in the dorsal horn were strongly immunoreactive to the GABA serum. Certain cells in the ventral horn have moderate numbers of labelled synaptic boutons on the perikarya, but very few GABA labelled terminals were found on putative motoneurons. The immunoreactive ependymal cells appeared to have a ventrolaterally directed axon. The glycine antiserum labelled small and intermediate cells in the dorsal grey, large, elongated cells in the median region, and varying sized cells in the ventral grey. The numbers and density of immunoreactive cells and neuropil structures in the ventral horn were fewer and lower than in GABA-stained sections. The median large cells had a thick ventrolateral process. The ventral intermediate cells were often found near putative motoneurons. Labelled synaptic boutons were present on most ventral cells including putative motoneurons and interneurons. Abundant distribution of cells immunoreactive to both antisera suggest important roles of both GABA and glycine as neurotransmitters for controlling swimming movements in teleosts. PMID- 8514922 TI - American Dairy Science Association 88th annual meeting and Northeast APSA/ASAS annual meeting. College Park, Maryland, June 13-16, 1993. Abstracts. PMID- 8514923 TI - Pressure sore prevention and wound management policies. PMID- 8514924 TI - The experience of a community characterized by violence: implications for nursing. AB - Social situations make a person vulnerable to mental illness. These situations include circumstances such as poverty, family instability and inadequate nutrition. A combination of these circumstances predisposes exposed people to developing unhealthy ways of coping with stress. Violence is seen as a way of managing stress, but also as a factor causing stress. An example of unhealthy ways of stress management in the current South African society is the violence that leads to unrest which has affected different communities in a short space of time. The aim of this study was to explore the experience of a community exposed to violence and to identify implications for nursing. An exploratory contextual study was undertaken with the purpose of generating meaning regarding the experience of a community characterized by violence. The phenomenological method of interviewing was used to gather data. The target population consisted of a township community of 228,000. Ten respondents were interviewed in total, selected by the convenience purposive sampling method through intermediaries. The interviews were recorded on tape and later transcribed verbatim. Data were analysed by the method of content analysis. The results were centred on the respondents' and their families' experiences of violence since March 1990. The results indicated four types of experiences for all people exposed to violence: psychological, spiritual, physical and behavioural experiences. The experiences of interactions with the internal environment (psychological, spiritual and physical experience) were predominantly negative, except for only two positive spiritual experiences (improvements in the people's faith and in the employer employee relationships). On the other hand, experiences of interactions between the internal and external environments, namely behavioural experiences, were both negative and positive. The negative experiences included pretence, thuggery, scapegoating and harassment. The positive experiences included solidarity, bravery and increased appreciation. The presence of positive experiences in both environments brought about new insights; that is, that even though most of their internal environment and part of their external environment is bleak and hopeless, the victims of violence still have the will to survive and live a normal life like other people. This positive attitude supplies the psychiatric nurse with a point of entry to bring about positive change that acts as a support for the community exposed to violence. Possibilities of applying the results of this study in education, practice and research in the health field became evident. PMID- 8514925 TI - Towards a reconceptualization of hope for patients with a diagnosis of cancer. AB - Recent years have seen increased attention given to examining the phenomenon of hope in patients with metastatic cancer. One of the results of this activity has been a greater appreciation of the significance of hope for the dying patient. However, there are many questions about the experience of hope and its impact on the lives of patients with cancer which remain to be answered. This paper discusses how hope is currently conceptualized in the nursing literature, and considers the implications that this conceptualization has for how we care for cancer patients. Some alternative ways of looking at the experience and the impact of hope are also discussed. PMID- 8514926 TI - Patient education at 25 years; where we have been and where we are going. AB - In the past 25 years the theory and research base for patient education has become considerably richer. Definition of a core of educative functions has now been accomplished for most major disease entities or health problems, and standards of practice developed for a few. In the United States, there is very inadequate information about the degree to which patient education is delivered, and institutional supports for it seem to have varied with fiscal conditions. The reimbursement system for health care has not explicitly supported patient education or the outcomes it could achieve. While there has been growth in instructional approaches, it would be charitable to say that there is a broad and well-informed view of potential approaches or an organized research and development function to get these approaches on line. If predictions of patient focus for business and ethical reasons are realized, a major shift in environment could occur, supportive of patient education. Clearly, there is little evidence that patient education represents a mature technology or that it is delivered at acceptable standards to all those who need it. Patient education content in key nursing textbooks published between 1988 and 1992 is analysed to examine the degree and character of conceptual penetration. PMID- 8514927 TI - Voluntarism: is it a useful concept for health education in the accident and emergency department? AB - As the year 2000 looms closer, the emphasis on health education as a means of attaining the 38 targets for 'Health for All' increases. Despite various initiatives, little, if any, progress has been made in narrowing the health divide. Currently, terms such as 'self-care', 'individual responsibility' and 'community empowerment' are often used with emphasis on individual freedom to choose. The author contends that to assume all individuals have that freedom and act voluntarily, is to deny the impact of social structure on health. Health education and the concept of voluntarism will be critically examined from the perspective of nursing in an accident and emergency department. PMID- 8514928 TI - Applicability of Orem's conceptual framework: a cross-cultural point of view. AB - Orem's conceptual framework for nursing is analysed and evaluated for its applicability in Chinese nursing practice. The appropriateness of Orem's nursing theory for application in Chinese nursing practice is determined through an examination of its completeness, compatibility, practicality and feasibility. Some insights and recommendations are offered for consideration. PMID- 8514929 TI - Mitral valve prolapse and its effects: a programme of inquiry within Orem's Self Care Deficit Theory of Nursing. AB - The optimum growth and scientific progress of nursing knowledge during the next century will depend upon the development and execution of focused programmes of clinical and theoretical research. The planning and design of such programmes must originate with the clear definition of nursing research questions. Nesting such questions within established theoretical frameworks provides a nursing context, lends precise language and suggests relevant variables for study. The development of a sequence of related studies exploring and describing the self care needs of people with symptomatic mitral valve prolapse illustrates one such systematic research programme. Orem's Self-Care Deficit Theory of Nursing was used as a theoretical framework for four completed studies which describe one population's need for nursing assistance. The evolving nature of the research programme and plans for future research are discussed. PMID- 8514930 TI - The place of the family in mental health nursing: past, present and future. AB - The importance of the family system has, in recent years, been de-emphasized in the planning and delivery of mental health services. A sample of the psychiatric nursing literature over the last 4 decades is reviewed to reveal that this is not a new phenomenon with regard to psychiatric nursing practice. The shortcomings of such a de-emphasis are discussed, some exceptions to the rule are described and some suggestions for future development of family interventions by mental health nurses are made. PMID- 8514931 TI - Audit: an exploration of some tensions and paradoxical expectations. AB - There can be very few nurses, at the moment, whose daily activity is not in some way influenced by the notion of audit and related concepts. Yet despite an impressive growth in the literature relating to audit, conceptual clarity on a number of key issues remains elusive. This paper suggests that there are major tensions inherent in much of the current thinking about audit. In outlining the arguments supporting our position, we term these tensions primary and secondary. The potential effects of ignoring such tensions are illustrated by reference to the development of day hospital care for older people in the United Kingdom. This is used to highlight a number of paradoxical expectations and deleterious consequences for day hospital services which have arisen from a failure adequately to address a number of fundamental questions. The lessons to be drawn are then applied to audit in general, with particular reference to services for individuals with on-going health care needs. PMID- 8514932 TI - Leadership in the nursing unit: relationships with nurses' well-being. AB - The head nurse occupies an important position in the nursing unit. Concerning leadership style, a distinction is traditionally made between consideration and initiating structure. Sometimes a third style is distinguished as well, namely 'production-orientated' leadership. In a study of 561 nurses from 16 general hospitals in The Netherlands, the influence of two leadership styles upon the reactions of nurses (job satisfaction, experienced meaningfulness, health complaints and absenteeism) to their work situations was examined, namely the styles of social (i.e. consideration) and instrumental leadership (a combination of the styles initiating structure and production-orientated). The separate effects of the two styles were studied, as well as the connection between combinations of leadership styles and reactions. The results indicate that social leadership contributes positively to nurses' reactions to their job. Instrumental leadership, on the other hand, leads to health complaints. From the analyses of combinations of leadership styles it appears that nurses are most satisfied if the head nurse pays much attention to both dimensions of leadership. For health complaints, a tendency in this direction is also found. Finally, it becomes clear that nurses with a great need for autonomy prefer a different type of leadership from nurses with little need for autonomy. PMID- 8514933 TI - Theory to practice: developing a Rogerian-based assessment tool. AB - Nursing models are invaluable in the direction they provide for nursing practice, education and research. The growth and development of the nursing profession is enhanced when its practice is guided by nursing theory. Rogers' Science of Unitary Human Beings is appealing to nursing because of its open-systems perspective and focus on holistic and individualistic care. Rogers' model is utilized to develop a nursing assessment tool that may be used in a variety of situations. The Rogerian-based assessment tool is used to gather data from a postpartum mother experiencing the challenges of her first newborn. Problems incurred while developing and utilizing the tool are discussed. Rogers' model is shown to be practical and effective in this case study. PMID- 8514934 TI - The relationship of nursing theory and research: the state of the art. AB - Recently, the relationship between theory and research has received more attention. It seems that in the past 10 to 15 years more research studies have been published that are more or less conceptualized within (nursing) theories. However, it is not always clear how the theory has been used. The purpose of this study was to analyse the role of theory in nursing practice research. To this end, papers published in six nursing journals between 1986 and 1990 have been studied. It can be concluded that, in comparison with earlier analyses, the use of theories in nursing research studies has increased (from 13% to 21%), but the use of nursing theories has not become more frequent. However, the testing of nursing theories is minimal. On the other hand, research results are being cumulated progressively in regard to theory or to other research. PMID- 8514935 TI - Triangulation: a means of reconciliation in nursing research. AB - The nursing profession has adopted many of its theoretical foundations, including research approaches, from other academic disciplines. This has resulted in the acceptance of one epistemological perspective to the exclusion of others. In this context, the evolution of nursing research reflects a rather conservative approach. The quantitative approach was the dominant paradigm of the 1950s, 1960s and during the 1970s and 1980s the research approach has been increasingly located in the qualitative paradigm. It is noted that each research perspective has several inherent differences which give rise to a specific type of research endeavour. Within the literature there is general support for the separateness of the quantitative qualitative paradigm. However in accepting the inherent differences between the two methods, nurse researchers have been concerned that neither method in isolation from the other will truly provide an understanding of human beings and of their health-related needs, problems or nursing care. Triangulation as a research strategy represents a means of integrating the two research approaches. Triangulation, first used in 1959, is defined as a combination of multi methods in a study of the same object or event to depict more accurately the phenomenon being investigated. The literature exploring the merits of triangulation is incomplete. However, it is reported that triangulation, by reconciling the paradigmatic assumptions inherent to quantitative and qualitative methods, provides rich and productive data. Triangulation does offer an alternative to the bi-polar quantitative and qualitative approaches and a means of reconciling the two methodological encampments. PMID- 8514936 TI - Identifying alternative linkages among philosophy, theory and method in nursing science. AB - The major concerns expressed in the literature regarding the development and expansion of nursing science stem from questions related to 'what sorts of science' and 'which scientific methods' are appropriate for nursing. While there is a sector of nursing's scientific community that advocates a unified approach to philosophy and method, a growing sentiment for the position of philosophical and methodological pluralism is apparent. This paper addresses the nature of scientific pluralism by presenting a framework for alternative linkages possible among the philosophy, theory and method appropriate for nursing science. The nature of nursing knowledge that is produced within the discipline will thus depend on various forms of alternative linkages adopted by nursing scientists in addressing nursing's scientific questions. In turn, such pluralism presents problems of choice to nurses in practice with respect to knowledge utilization. PMID- 8514937 TI - Can we insulate trainee nurses from exposure to bad practice? A study of role play in communicating bad news to patients. AB - This paper investigates the effects of three different role models in teaching trainee nurses to cope with the sensitive task of communicating a traumatic event to patients or their relatives. This is a long-standing problem with a high level of dissatisfaction within the field of nurse training. This study, in contrast to other studies of telling bad news (TBN), has focused on the person who gave rather than received bad news. This study also reinforces the view that role play and role modelling are not only effective learning methods in nurse training but are natural methods of learning in the profession. Student nurses are constantly exposed to other people's attempts at caring. Eighteen student nurses were randomly selected from a total student intake of 66 students for study in depth. Nine main skills were identified in a TBN task. Six student nurses were exposed to negative examples of a novice telling bad news, six to an expert model doing it and six to both models. The results showed that nurses learned quickly from role models, whether it was the negative instance of a poor model or the positive instance of an expert model or a combination of both. No significant difference in effectiveness between the three models was observed. The findings are discussed with reference to implications for nursing education in general. PMID- 8514938 TI - The perspective of student nurses and their perceptions of professional nursing during the nurse training programme. AB - This study was undertaken to identify what preconceptions student nurses have of nursing when they enter the nurse training programme at university and how these views change during the course. The term 'perspective' was chosen to describe how the students view themselves, their environment, way of thinking and feeling about nursing and the opportunity to act in nursing and educational situations. The data for this ethnographic study were collected by means of participant observations, interviews and document analysis. The subjects were 41 nursing students enrolled in the nursing programme at a school of nursing in the Swedish Midlands. Four different ways of perceiving the nursing function are discerned from the descriptions of the task, status and personality traits associated with nursing. The results indicate that student nurses perceive nursing in a very traditional way and that their perceptions tend to be stable during th training period. The findings suggest that about one-third of the student develop a new perspective and a self-concept as a nurse during the course, but the traditional image of the nurse persists. PMID- 8514939 TI - Identifying a role for the nurse teacher in the clinical area. AB - This paper describes a project which sought to identify a model to provide direction for nurse teachers working in clinical areas. Using an action research approach, the clinical teaching role was explored by working with trained nurses on one psychiatric ward. Two action plans were formulated, implemented and evaluated. The first involved working towards improving the learning environment and the second towards developing the ward manager's teaching role. The author concludes by recommending that teachers need to adopt a multi-dimensional role in the clinical area working as researchers, teachers and change catalysts. PMID- 8514940 TI - Expectation and evaluation of occupational health nursing services, as perceived by occupational health nurses, employees and employers in the United Kingdom. AB - A structured questionnaire was used to investigate the relationship between expectation and evaluation of occupational health nursing services as perceived by providers (nurses) and receivers (employers and employees) in the United Kingdom. The response rate was 66.55% (254) from nurses, 51.32% (194) from employees and 44.97% (170) from employers. Data from 144 triads of nurse, employer and employee were used to test 13 null hypotheses, which were all rejected. The strong positive correlation between nurses', employers' and employees' expectations and evaluations indicates that, on the whole, their expectations were met. However, there were differences in the extent to which this was so and the level of expectation varied between groups. Nurses perceived themselves as not meeting their high expectations as well in non-traditional (care-supportive) as in traditional (care-orientated) services. On the whole, employers had significantly lower expectations than nurses, except in the area of care and treatment. Employees had high expectations of preventive services, but their lower evaluations indicate that these were not met. Discussion of these and other findings suggests that employers need education on the value and scope of occupational health nursing, and a model may assist nurses' conceptual understanding of it. PMID- 8514941 TI - An examination of touch between nurses and elderly patients in a continuing care setting in Northern Ireland. AB - The use of touch is an inherent part of nursing practice. This investigation examined the amount and type of touch received by elderly patients from nurses. It also attempted to assess elderly patients' perceptions of instrumental and expressive touch given by nurses. The Extended Model of Interpersonal Interaction formed the conceptual framework for the study. Non-participant observation and semi-structured interviews were the methods employed for data collection. Results tentatively suggest that most nurse-patient touch interactions in a care of the elderly ward are instrumental in nature. Expressive touches are predominantly given to body extremities. The gender of the nurse initiating touch and the part of the body touched influence the elderly patients' perception of the touch interaction. In particular, expressive touching behaviours by nurses that involve the leg, face and around the shoulders are perceived as uncomfortable. The only touching behaviour perceived as comfortable by all respondents was instrumental touching of the arm and shoulder by a female nurse. Elderly patients may misinterpret the goal or the motivation behind touch initiation by a nurse. Therefore, an awareness and a sensitivity towards elderly patients' needs and desires for tactile communication are required by nurses. PMID- 8514942 TI - The greying of the professional nurse. PMID- 8514943 TI - Robbing Peter to pay Paul--or, stealing faculty hurts us all. PMID- 8514944 TI - History, nature, and nurture. PMID- 8514945 TI - Friendly international cooperation. PMID- 8514946 TI - Incompetent, unethical, or illegal practice--teaching students to cope. PMID- 8514947 TI - Responsibilities of nursing education: the lessons of Russell v Salve Regina. AB - In August 1985 Sharon Russell was dismissed from Salve Regina College just before her senior year of nursing education. The reasons given for her dismissal focused on Russell's obesity and her inability to lose weight. The issues raised by this case pose important questions that nursing programs and nurse educators must address. This article explores the questions raised by Russell: (1) What constitutes substantial compliance with both academic and nonacademic performance criteria in a contract between a student and an educational institution? (2) What duties to preserve the privacy interests of students may be imposed on programs and educators? Ms Russell's case has been settled. She established that she had met the terms of the contract and substantially complied with the academic and nonacademic criteria of the nursing curriculum. She was awarded monetary damages for the college's breach of contract in nonperformance of an agreement to educate. She did not prevail in her claims of intentional infliction of emotional distress or invasion of privacy. She did, however, put nursing education programs on notice that colleges and universities are not immune from these contractual challenges and must demonstrate respect and consideration for student's personal concerns. PMID- 8514948 TI - Medicare and the financing of nursing education: implications of Board of Trustees v Sullivan. AB - In 1991 a federal court decided a case of first impression about the appropriateness of reimbursement to programs of nursing education under Medicare. The court confirmed that the University of Mississippi could continue receiving Medicare reimbursement for a proportionate share of the costs of clinical education for nurses in its affiliated hospital. However, it ruled that the $2 million in costs for classroom nursing education incurred by the School of Nursing would not be reimbursed despite the fact that both the hospital and nursing school were controlled by the same entity, the university system. This article reviews the court's decision in Board of Trustees of State Institutions of Higher Learning v Sullivan within the context of the available nursing literature on this topic. It describes the provisions of the Medicare statute, which allow for reimbursement of programs of nursing education, and the implications of the court's decision for nursing education. Finally, it suggests directions for additional research and discussion about the availability of an additional source of federal funding. PMID- 8514949 TI - An economic paradigm for nurse practitioner program development. AB - In 1987 a collaborative nurse practitioner program was developed and implemented by George Mason University, a public institution, and The George Washington University, a private institution. Three economic factors affecting decisions related to the development of the collaborative program are discussed: (1) optimal use of resources, (2) consumer and institutional utility, and (3) demand for the program. Optimal use of resources was based on collaboration in the areas of faculty and administrative resources and existing curriculum, thereby reducing the cost burden at each institution. From the perspective of consumer and institutional utility, the program was structured financially to enhance the well being of students and both institutions. Finally, the consumer demand for the program was addressed by maintaining the higher proportion of credits at the lower-cost institution, thus enabling more students to afford the program. The success of the institutions in addressing the economic factors noted above can serve as a paradigm for program development in other universities and graduate programs. PMID- 8514950 TI - A statewide instructional television program via satellite for RN-to-BSN students. AB - Instructional television (ITV) is providing the bridge between nursing educational needs and health care resources, allowing nurses in rural areas to attend a university without leaving their jobs or relocating. This article describes the experiences of developing a baccalaureate degree completion program for nursing via satellite. To create a successful distance education program, it was necessary to re-examine curricular structure, objectives, course descriptions, the basis of course sequences, teaching strategies, library resources, and learner needs. It was vital to modify the student and faculty support services on campus for use with distance learners. PMID- 8514951 TI - A review and integration of knowledge about faculty research productivity. AB - The nursing literature is replete with commentary and opinions about the research and scholarly productivity of nursing faculty. There are also a number of research studies on several aspects of faculty productivity. However, a scholarly critique and integration of research on this topic is lacking. This article reviews the literature on faculty research productivity and synthesizes the findings to present recommendations for promoting nursing faculty research and scholarship. PMID- 8514952 TI - Burn-out in hospital nurses: a comparison of acquired immunodeficiency syndrome, oncology, general medical, and intensive care unit nurse samples. AB - Previous research has shown that job-related stress and burn-out are associated with high levels of demand placed on the worker, especially in situations where influence is low. This study examined burn-out among nurses working on acquired immunodeficiency syndrome (AIDS) special care units (SCUs), oncology SCUs, medical intensive care units (ICUs) and general medical units to measure the extent to which delivery method (SCU, ICU, and general unit), patient diagnosis, or other key personal and work-related characteristics were associated with the level of distress in these nurses. A sample of 237 nurses from 18 units in seven hospitals were surveyed using the Maslach Burnout Inventory. This study showed no significant differences in burn-out scores across nurse samples representing variations in patient diagnosis and delivery method. Specifically, nurses on AIDS SCUs, oncology SCUs, medical ICUs, and general medical nursing units reported similar levels of distress on the burn-out subscales. There was one exception: medical ICU nurses scored significantly lower on the Personal Accomplishment subscale (P < .001). Regression analyses for the Emotional Exhaustion and Personal Accomplishment subscales indicated that greater job influence had a significant protective effect on emotional exhaustion and enhanced personal accomplishment (P < .05). As expected, job tension was a key predictor of exhaustion (P < .001), and being white was associated with greater feelings of accomplishment (P < .002). Working in a medical ICU continued to show a negative impact on accomplishment when race and other important covariates were controlled for (P < .05), and working on an AIDS SCU was predictive of exhaustion in a multivariate context (P < .05). PMID- 8514953 TI - Meeting the nation's health objectives: special project grants. AB - The purpose of this article is to encourage and motivate the nursing community to become active partners with the US Public Health Service in meeting the health objectives for the nation by the year 2000. The three major public health goals to be achieved during the 1990s are identified. The Special Project Grant Program in the Division of Nursing, Bureau of Health Professions, Health Resources and Services Administration, United States Public Health Service, is described as an opportune resource for nurses to use in their search for funds to demonstrate the ability and capacity of nursing to promote health and prevent disease in this nation's high-risk and underserved populations. Several descriptions of highly successful grants, funded by the Division of Nursing's Special Project Grant Program, are featured as motivating examples of creative and original endeavors by nursing to assist in meeting this nation's health objectives during the 1990s. PMID- 8514954 TI - The evolution of peer education: where do we go from here? PMID- 8514955 TI - The power of peer health education. AB - Peer education on college and university campuses has grown from self-educated students responding to campus health issues to state-of-the-art health education and motivational models designed to empower students to help each other promote positive health beliefs and behaviors. Peer education models come in many paradigms and often represent the best use of campus resources for specific needs. Model peer education efforts are based on carefully trained and closely supervised programs that ensure continuing quality improvement. Health educators are now exploring more comprehensive training and delivery models that encompass the complex nature and relationship, among risk behaviors, life skills, and the social pressures that have an impact on students' lives. Future peer education possibilities will involve many facets of college life created by people who care and believe that prevention is the essential component for empowering future leaders on both a personal and professional level. PMID- 8514956 TI - Total quality assurance and peer education. AB - To promote program quality assurance, the Office of Health Promotion and Education at Penn State University evaluated peer health educators' presentation skills. Professional staff and experienced peer educators used an instrument tested for interobserver reliability to evaluate effectiveness in three skill areas: knowledge, delivery, and sensitivity. Each skill was rated, using a 4 point Likert-type scale. Knowledge included measures of preparation, subject knowledge, and ability to respond to questions knowledgeably; delivery included measures of clarity of directions, pacing, and transitions, appropriate and challenging questions, cooperation with co-facilitators, and enthusiasm; and sensitivity included comfort level, establishing trust in the group, nonjudgmentalism, appropriate use of humor, and nonsexist/nonheterosexist language. The evaluation teams observed and reviewed 18 work-shops conducted by 24 peer educators. Of the 24 educators evaluated, only 4 scored below 85%, the threshold for acceptable performance, and most scored above 90% in competency. Once baseline data had been gathered, the professional staff established a requirement that peer educators who did not meet this threshold must conduct their next two presentations with experienced peer educators who had met or exceeded it, and that professional staff members should work with students individually to improve skill levels. Evaluation criteria and threshold rates are to be reviewed each year. PMID- 8514957 TI - A review of evaluations of peer education programs. AB - Although peer education programs have existed on the college campus for many years, few evaluations of their effectiveness have been made. The author reviews the brief literature on process and outcome evaluations and offers suggestions to encourage evaluations that will yield more accurate and useful information. Such information is particularly important at a time when many universities face budgetary constraints that put these programs and those who administer them at risk when programs and services are curtailed. PMID- 8514958 TI - Planning for the future of peer education. AB - In 1970, the University of Massachusetts began a pioneering program using student peer educators in the fields of alcohol and other drug use and sexuality. Peer educators continue to have an impact on the campus through their creative and innovative health-promotion interventions. These student educators are valued as agents of change because they can communicate effectively with their contemporaries in ways that professional staff members cannot. The current restructuring of the UMass, Amherst, peer program that collapsed three individual topic-based programs into one integrated 2-semester course is an appropriate response to critical personnel problems and economic realities. The long-range goals for peer education respond to an agenda that supports and encourages the value of peer education on campus and accepts the need for flexibility in providing for program continuity and vitality. PMID- 8514959 TI - Refining your peer education program. PMID- 8514960 TI - Peer education and the deaf community. AB - Gallaudet University, the world's only liberal arts university for deaf students, has recently established a peer health education program. This program is unique because of the population it is designed to serve and the rich culture within which the program exists. Although the program is still in its early stages, it has received an enthusiastic response from students and from the greater campus community. PMID- 8514961 TI - Peer education in the residential context. AB - Research on HIV-prevention education with college students has demonstrated that interventions that provide only information do not bring about risk-reducing changes in behavior. Given the chronic nature of HIV infection, as well as data that show that students do not consistently use condoms and practice safer sex, peer education programs dealing with sexually transmitted diseases need to focus on strategies that have demonstrated success in encouraging behavioral changes. A one-on-one program at the State University of New York (SUNY) at Stony Brook has shown how students' understanding of risk reduction can help bring their behavior into accord with their knowledge. PMID- 8514962 TI - Training opinion leaders to promote safer sex. AB - Training opinion leaders in a men's residence hall in a brief program focused on communication and life skills is an effective way to stimulate peer discussions on HIV prevention and risk reduction and appears likely to have positive influences on behavioral change or intention. The program at the University of Wisconsin-Madison was extremely cost-effective and generated more than 350 conversations in a single residence hall in 1 month. This limited intervention revealed several key indicators of risk reduction. We believe that larger, more refined programs over a longer period will produce sustained prevention benefits and changes in the peer norms that so strongly influence behavior. PMID- 8514963 TI - Athletes as rape-awareness educators: athletes for sexual responsibility. AB - Sexual assault, including both date rape and gang rape, is an area of great concern for college students today. The University of Maine is addressing this serious national problem through a unique peer education program that enlists athletes as role models for appropriate social and sexual behavior, as well as of physical strength, agility, and stamina. PMID- 8514964 TI - Sex, truth, and womantalk: what your mother never taught you. AB - This article describes a project based on feminist theory and pedagogical techniques that used students as peer facilitators. The program was designed to maintain and enhance health-promoting sexual behaviors among female college students in response to the premise that women's gender socialization limits their ability to translate knowledge about HIV transmission and prevention into risk-reducing behavior. The project used workshops and small support groups to focus student attention on sexuality, gender socialization, values clarification, assertiveness training, and intimate negotiation. PMID- 8514965 TI - A student competition to develop an innovative alcohol education strategy. AB - The authors report on a competition that emphasized peer health education and alternative activities to encourage alcohol-free student behavior during a weekend traditionally associated with the abuse of alcohol. The project was designed to promote activities that would (1) be consistent with education/behavior change theories; (2) generate student "ownership," energy, and participation; (3) use the creativity and resourcefulness of students; and (4) involve as many university staff members, departments, and community resources as possible. More than seven university departments and 1,200 students were involved in the project. PMID- 8514966 TI - Complex issues for sexual assault peer education programs. AB - Peer education programs dealing with sexual assault are important for starting dialogue and improving students' awareness. If a peer education effort is to be effective, the college or university must have written policies condemning sexual assault, investigative and reporting procedures, and comprehensive sexual education and information programs. Experience at Brown University revealed the necessity of providing peer educators with opportunities during initial training for open and honest dialogue on the politics of campus rape, facing issues of power and dominance, women's dress as a factor in rape, and the distinction between victim and survivor. These discussions can be strained and frustrating, but they are a necessary step in resolving conflict among the peer educators and helping them provide a consistent message. PMID- 8514967 TI - A case study of a successful health advocate program. AB - This case study describes the health advocate program of Olin Health Center at Michigan State University. The health advocates are the peer branch of the university's health education/public health service. Since initiation of the program in January 1986, more than 125 students have participated in the training and service, for which they receive academic credit. This case study describes the background, development, and evaluation strategies of the health advocate program and offers recommendations to those who are interested in developing a similar program. PMID- 8514968 TI - Peer-based HIV risk assessment: a step-by-step guide through the teachable moment. AB - Peer educators in HIV prevention have influence with other students beyond the narrowly defined traditional activities of workshop presentations of outreach projects. Training HIV prevention peer educators to be prepared for the "teachable moments" when other students seek their assistance on assessing risk for HIV infection is a necessary new emphasis in the training curriculum. HIV risk assessment can be approached as an educational intervention that requires interpersonal skills, but does not cross the invisible barrier into "counseling." PMID- 8514969 TI - Professionals' experiences of peer education. PMID- 8514970 TI - Removal of nitrogen and phosphorus from swine wastewater by intermittent aeration processes. AB - Nitrogen and phosphorus removal in a methane fermentation plus activated sludge method type pig farm (M-III) with an intermittent aeration process (IAP) was evaluated in comparison with a continuous aeration process (CAP) based on the full-scale and bench-scale experiments. Operation conditions for the treatment system were the same except for the aeration program (in the CAP), a consecutive 24-hr aeration was used, whereas in the IAP, the aeration and non-aeration periods were alternated at intervals of 3:1 hr. BOD and TOC removal efficiencies with the intermittent aeration were as high as those with the continuous operation (92-98%). In the removal of nitrogen and phosphorus, large differences between IAP and CAP were observed. At an influent T-N/TOC ratio of 0.1, removal efficiencies for T-N in the bench-scale IAP was 70%, and for T-P was 22%, respectively. At an even higher influent T-N/TOC ratios of 0.3-1.0, the removal efficiencies for T-N were decreased to about 59-61%, whereas that for T-P were 0.3-13%. In a full-scale plant, removal efficiencies for T-N with IAP and CAP were 42% and -0.09%, respectively. The results of this study show the successful performance of a simple IAP for piggery wastewater: simultaneous, one-sludge denitrification with nitrification in single-activated sludge reactor in a pig farm. PMID- 8514971 TI - Abnormal thyroid function test results in patients with Fisher-Evans syndrome. AB - Thyroid function was evaluated in patients affected by Fisher-Evans syndrome (FES) and compared to that of patients affected only by autoimmune hemolytic anemia (AIHA) and to that of patients affected only by idiopathic thrombocytopenic purpura (ITP). The study population consisted of 20 patients with FES, 44 with AIHA and 20 with ITP. All patients were examined for thyroid function abnormalities and thyroid autoantibodies. Abnormal thyroid function test results were observed in 40, 25 and 10% of the patients, respectively. The prevalence of antithyroid antibodies (ATA) in FES was 25%; this is higher than the sum of the prevalences of ATA in patients affected only by AIHA (11.4%) or only by ITP (none). Subclinical primary hypothyroidism and hyperthyroxinemia with or without hypertriiodothyroninemia, with TSH serum levels below normal, were present in 20% and 10% of patients affected by FES, respectively. Of the former, 75% were positive for ATA. These results: i) confirm the high prevalence of abnormal thyroid test results in patients affected by AIHA, ITP and FES; ii) demonstrate the higher prevalence of autoimmune hypothyroidism in FES; iii) lead to the possibility of including FES as one of the multiple autoimmune syndromes. PMID- 8514972 TI - Relationship between serum CA 125 levels, endometrial thickness and corpus luteum function in different stages of ovarian activity. AB - CA 125 is a cell surface antigen expressed in some derivatives of celomic epithelium, predominantly in ovarian cancer cells. However, it has also been detected in serum of healthy women and in patients with benign gynecologic diseases. The exact source or sources of the circulating levels of CA 125 and their elevations are not known. In the present study, the relationship between serum CA 125 levels, ovarian steroidogenesis and endometrial thickness is investigated at different periods: 1) mid-follicular, 2) midcycle, and 3) midluteal phases in normal cycles of fertile women, in patients stimulated for intrauterine insemination (IUI) and in patients stimulated for in vitro fertilization (IVF). Only in patients with mild and moderate ovarian hyperstimulation (OHSS) of the IVF group were luteal phase CA 125 levels (149.7 +/- 24.4 U/ml) significantly higher than midfollicular (21.2 +/- 1.9 U/ml) and midcycle phase levels (24.4 +/- 2.5 U/ml) (p < 0.001). The mean midcycle estradiol and midluteal progesterone concentrations in patients stimulated for IUI and IVF were significantly higher than those of normally cycling women (p < 0.001). Mean endometrial thickness in patients stimulated for IVF was significantly higher than in patients stimulated for IUI and normally cycling women (p < 0.001). Midluteal CA 125 levels correlated with midcycle endometrial thickness (r = 0.585, p < 0.05) and midluteal P levels (r = 0.497, p < 0.05) in patients with OHSS of IVF group. This correlation was not observed in patients who had no signs and symptoms of OHSS during stimulation for IVF and in patient stimulated for IUI and the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514973 TI - Acromegaly: an epidemiological study. AB - Although morbility and mortality in acromegaly are higher than in the general population, there have been very few previous epidemiological studies. This study tries to answer "why". Seventy-four patients affected by acromegaly in Vizcaya (Spain) between 1970 and 1989 were considered for an epidemiological study. The prevalence of known cases at the end of 1989 was 60 per million inhabitants. The average incidence of newly diagnosed cases was 3.1 per million people per year. Unexpectedly, acromegaly was more frequent in women (n = 48) than in men (n = 26), with a ratio of 1.8:1. Mean age at diagnosis was significantly higher in women (46.1 +/- 2.2 yr) than in men (39.5 +/- 2.2 yr) (p < 0.05) There was a positive correlation between age at diagnosis and the estimated duration of the disease (r = 0.56, p < 0.05) and a negative one between age and basal GH serum levels (r = -0.52 p < 0.002). The age at diagnosis was significantly higher in patients with invasive tumors (grade III and IV) than in those with enclosed tumors (grade I and II) (47.7 +/- 1.8 vs 40.1 +/- 3.3 p < 0.05). In general, mortality was higher than the expected for the control population (standardized mortality ratio, SMR = 3.2, 95% confidence interval. Cl = 1.55-5.93). However, mortality was higher in men (SMR = 7, 95% Cl = 2.81-14.4) but not in women (SMR = 1.4 95% Cl = 0.29-4.17).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514974 TI - Modulation of pituitary insulin-like growth factor-I bindings in rats bearing somatomammotrophic tumors. AB - To clarify the hormonal regulation of pituitary insulin-like growth factor-I (IGF I) bindings, we examined the continuous effect of growth hormone (GH) on [125I] IGF-I binding sites, using rats bearing transplantable GH-secreting rat pituitary tumor cells. A total of 24 female Wistar-Furth rats (4-week old) was divided into four groups (n = 6). The first group rats were control (C). The second group rats were injected subcutaneously with 3 x 10(6) GH3 pituitary tumor cells (GH). The third group rats were thyroidectomized (Tx) and the fourth were dual-treated (GHTx). The brain, pituitary gland, liver, and kidney were immediately subjected to quantitative receptor autoradiography after a 4-week treatment period. Using kinetic experiments, GH rats had higher Bmax values of specific [125I] IGF-I binding sites in the anterior pituitary gland and Tx rats had lower Bmax values than control rats. Two-way analysis of variance among the 4 groups was examined. The effects of both GH and Tx treatment on [125I] IGF-I binding Bmax were observed only in the anterior pituitary gland and not in the other tissues examined. There were no differences in the Kd values of the binding sites. These data indicate that continuous GH excess selectively up-regulates the number of pituitary IGF-I binding sites in vivo, and that this may play a role in feedback regulation of the GH-IGF-I axis. PMID- 8514975 TI - Maternal decidua and fetal membranes contain immunoreactive neuropeptide Y. AB - The aim of the present study was to evaluate whether the various intrauterine tissues contain immunoreactive neuropeptide Y (NPY). Previous observations showed that human placenta produces NPY and that it may play a local role. Using a polyclonal NPY antiserum and an immunofluorescent technique, sections of maternal decidua, amnion and chorion collected from a pregnant women at parturition were studied. An intense positive staining for NPY was observed in epithelial amnion cells and in chorionic cytotrophoblast. Some of the maternal decidual cells showed a weaker signal of immunoreactive NPY. In evaluating whether NPY may coexist with other hormones in these tissues, adjacent slices of decidua, amnion and chorion were stained with activin beta B subunit antiserum. In the various tissues a relevant number of cells showed positive signals for both NPY and activin. The present findings showed that the various intrauterine tissues contain NPY and that in a large number of cells of amnion, chorion and decidua the neuropeptide is colocalized with immunoreactive activin. In view of the physiological implications of NPY in the regulation of uterine contractility and of placental hormonogenesis, the present findings indicate a large distribution of NPY in the various intrauterine tissues. PMID- 8514976 TI - False positive 131I total body scan due to an ectasia of the common carotidis. AB - A cervical accumulation of radioiodine at Total Body Scan (TBS) in a patient who had been thyroidectomized for a follicular thyroid carcinoma led to unnecessary radioiodine treatment. Thyroglobulin measurements indicated constantly low levels. Following ultrasound scanning of the neck, echo-doppler examination of the cervical vessels and angiography with 99Tc, this area of increased activity at TBS imaging was shown to be due to an ectasia of the right common carotidis causing blood stasis and reverse flow. PMID- 8514977 TI - Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration. AB - Interleukin-6 (IL-6) is the main mediator of the acute phase response. Increased serum concentrations of the cytokine have been found in patients with nonthyroidal inflammatory disorders and infections. In 18 patients with subacute thyroiditis (SAT) evaluated within 1-2 weeks after the onset of the disease, serum IL-6 values, as assessed by an ELISA method having a limit of detection of 25 fmol/L, ranged 139.2-543.9 fmol/L (mean +/- SE, 287.2 +/- 28.2 fmol/L). These values were significantly higher than those of 25 normal healthy controls (mean +/- SE, 26.2 +/- 5.5 fmol/L, range < 25-99.4), 18 of whom had serum IL-6 values below the detection limit. The increase in serum IL-6 levels in SAT patients appeared to be related to the inflammatory disorder and not to thyrotoxicosis, because 18 Graves' disease patients and 13 patients with toxic adenoma or toxic multinodular goiter had significantly lower serum IL-6 concentrations (101.7 +/- 35.2 fmol/L, range < 25-251, for Graves' disease, 79.6 +/- 41.4 fmol/L, range < 25-168.5, for toxic adenoma, p < 0.001 vs SAT for both groups) despite the markedly higher levels of total and free thyroid hormones. Neither free T4 nor free T3 values were correlated with serum IL-6 levels both in SAT and Graves' patients. Twelve SAT patients were reevaluated 3-4 months later, after remission of the disease and at least one month after glucocorticoid withdrawal. At the final observation, all SAT patients showed a normalization of IL-6 concentration, which was undetectable in 8/12 (mean +/- SE, 22.8 +/- 5.4 fmol/L, p < 0.001 vs acute phase values).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8514979 TI - Endometrial estrogen and progesterone receptors within 2-14 days of missed menses in the human. AB - Serial changes in the endometrial levels of estrogen and progesterone receptors (ER and PR) were measured in 50 women from days 2 to 14 of missed menses and correlated with the plasma concentrations of hCG, progesterone and 17 beta estradiol. Both ER and PR of nuclei were higher than cytosolic proteins, with a shift in the ratio of nER/nPR to nPR from 4th day after missed menses. On Scatchard analysis of the cytosolic and nuclear binding proteins, two classes of proteins, corresponding to Type I and II, were found. While the increasing levels of hCG maintained luteal secretion of progesterone and 17 beta-estradiol at normal mid-luteal phase levels, a gradual increase in 17 beta estradiol from 9th day of missed menses was noted. This delicate balance between circulating levels of progesterone and 17 beta-estradiol and their nuclear receptors at early stages of pregnancy may be of significance. PMID- 8514980 TI - Growth hormone and insulin-like growth factor-1 in blood and urine as response markers during treatment of acromegaly with octreotide: a double-blind placebo controlled study. AB - Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and prolactin (PRL) in blood and urine were observed in 20 patients with acromegaly in a double-blind placebo-controlled 14-day clinical trial with the somatostatin analog octreotide. Hormones were determined by the same radioimmunoassays in blood and urine. Significant reduction of GH and IGF-1 during octreotide treatment compared to placebo was seen in blood but not in urine. Patients with diabetes mellitus, 2 of the 20 patients, showed notably increased urinary GH and IGF-1 in relation to blood levels. Therefore, results without the two diabetic patients were calculated, showing significant reduction of urinary GH and IGF-I during treatment on some, but not all observation days. The intraindividual variations of GH and IGF-1 were greater in urine than in blood. PRL levels were not significantly affected by octreotide either with or without the two diabetic patients. In conclusion, this study indicates, that GH and IGF-1 in blood are preferable to urinary GH and IGF-1 as response markers during treatment of acromegaly with octreotide. One disadvantage with urinary assessments of GH and IGF-1 in acromegaly seems to be the relatively higher excretion in patients with diabetes mellitus. PMID- 8514981 TI - Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study. AB - Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter. PMID- 8514982 TI - Therapeutical doses of salbutamol inhibit the somatotropic responsiveness to growth hormone-releasing hormone in asthmatic children. AB - In humans beta-adrenergic receptors mediate an inhibitory effect on somatotropic function, likely via stimulation of hypothalamic somatostatin release. Accordingly, salbutamol (SAL), a beta 2-agonist, given iv abolishes the GH response to GH-releasing hormone (GHRH) in adults. Taking into account that in bronchial asthma an alteration in the beta-adrenergic neural control of airways has been hypothesized, we aimed to verify whether, in asthmatic children, beta adrenergic activation inhibits or not GH secretion. To this goal, we studied the effect of therapeutical doses of SAL on GH response to GHRH in 15 asthmatic children (12 M and 3 F, 5.9-11.1 yr, pubertal stage I-II). All children underwent a GHRH test (1 microgram/kg iv). Moreover, in 7 children (group A), SAL was administered orally (0.125 mg/kg) 1 h before GHRH, while in 8 (group B) by inhaled aerosol (2 mg) 30 min before GHRH. Oral SAL (group A) abolished the GHRH induced GH rise (AUC, mean +/- SE 165.1 +/- 33.3 vs 959.9 +/- 158.1 micrograms/L/h; p < 0.03). In group B, the GH response to GHRH was only blunted by inhaled SAL (938.6 +/- 284.6 vs 1378.8 +/- 315.6 micrograms/L/h; p < 0.02). In conclusion, our data show that in asthmatic children, therapeutical doses of SAL exert a marked inhibitory effect on GH secretion. Further studies are needed to exclude detrimental effects of chronic treatment with beta 2-agonists on GH secretion and growth velocity in asthmatic children. PMID- 8514983 TI - Serum osteocalcin in metabolic bone diseases: what is its real significance? AB - This study has been carried out in order to elucidate the clinical significance of serum osteocalcin measurement. The changes of this marker paralleled those of serum total alkaline phosphatase activity (a marker of bone formation) following parathyroidectomy in hyperparathyroid patients with skeletal involvement. Furthermore, the percentage decrease of serum osteocalcin levels in respect to basal values (85 +/- 12), and the percentage decrease of serum alkaline phosphatase activity levels (82 +/- 7) were significantly lower (p < 0.001) in respect to that of the 24-h hydroxyproline/creatinine ratio (42 +/- 14) one week after parathyroid surgery. Instead, changes of serum osteocalcin levels were similar to those of serum free hydroxyproline (considered to be a marker of bone resorption) following acute calcitonin infusion in normal subjects. These results imply that the antibody used in our assay might recognize not only the entire osteocalcin molecule, but also small epitopes released during the process of bone matrix resorption. Alternatively, if we consider serum osteocalcin only as a marker related to some processes of bone formation, the experiment carried out on normal subjects strongly supports the evidence of calcitonin receptors in osteoblastic surfaces. PMID- 8514984 TI - Acute adrenocortical failure due to tuberculosis. AB - A 55-year-old woman presented with acute adrenal failure, active pulmonary tuberculosis and an enlarged adrenal mass which was subsequently removed surgically. Histopathologic examination disclosed adrenal tuberculoma. It was concluded that tuberculosis might result not only in chronic adrenocortical insufficiency but also in acute adrenal failure. PMID- 8514978 TI - Molecular biology of the regulation of hypothalamic hormones. PMID- 8514985 TI - Reduction of insulin resistance after correction of nonneoplastic ovarian virilization. AB - A 60-year-old woman with a progressive virilization for about 5 yr developed diabetes mellitus with elevated insulin levels (fasting insulinemia ranging 32.4 45.8 microU/ml). The marked increase of plasma testosterone (total 5.7-8.2 ng/ml; free 11.5 pg/ml) and other endocrine markers clearly indicated the ovarian origin of hyperandrogenism. Pelvic ultrasonography, computerized axial tomography, and direct examination of ovaries during laparotomy, showed no evidence of neoplasia. Microscopic examination and immunocytochemical investigations confirmed the diagnosis of hyperthecosis. After oophorectomy and regression of hyperandrogenism, fasting and postprandial blood glucose concentrations normalized in spite of persistently elevated levels of insulinemia (fasting values ranging 32.0-61.0 microU/ml). The present case suggests that pathological increase of testosterone can interfere with insulin-glucose balance impairing the peripheral sensitivity to insulin. PMID- 8514986 TI - Bilateral gonadoblastoma in a 9-month-old infant with 46,XY gonadal dysgenesis. AB - A 9-month-old infant with hypertrophic clitoris and separated urethral and vaginal opening was diagnosed as having 46,XY incomplete "pure gonadal dysgenesis". Examination of both gonads revealed gonadoblastoma and bilateral salpingo-gonadectomy and partial hysterectomy were performed. Patient is raised as a girl, and clitoroplasty will be done in next several months. The fact that gonadal neoplasia in our patient was found already at the age of 9 months, confirms the need for gonadectomy at the time of diagnosis in the patients with 46,XY gonadal dysgenesis. PMID- 8514987 TI - Clinical thyroidology 1992: "what do we really need'? PMID- 8514988 TI - Cellular models for the analysis of paracrine communications in parathyroid tissue. PMID- 8514989 TI - [Functional hypothalamic amenorrheas. I. Physiopathology]. AB - Functional hypothalamic amenorrhea are very probably due to a decrease of the frequency of the secretory pulses of LH, ie of GnRH. This decrease could be the consequence of a chronic hypersecretion of the corticotropin releasing hormone (CRH). CRH seems to act on the hypotalamic pulse generator of GnRH through the effect of the endogenous opioid peptides of the central nervous system. Opioid receptor antagonists restore normal pulse frequency of LH in most cases. Research is being done to try to elucidate the cause of the failure to such treatment: dopamine in among other mechanisms, supposed to play an essential role. PMID- 8514991 TI - [Respective diagnostic importance of hysterography and hysteroscopy in common uterine pathology]. AB - In order to evaluate the diagnostic effectiveness of hysteroscopy and hysterography in common uterine diseases. 175 cases of hysterectomy were reviewed. The preoperative diagnosis obtained by these two examination methods was compared with the pathologist's report. Statistical analysis showed a 97.3% sensitivity for hysterography (specificity 28.5%). The sensitivity of hysteroscopy was 89% and its specificity 50%. The results varied according to the pathology observed. The best results for myomas were obtained with hysterography, and those for localized disorders (hyperplasia, polyps, etc.) with hysteroscopy. PMID- 8514990 TI - [Functional hypothalamic amenorrheas. II. Clinical aspects]. AB - The most important causes of the functional hypothalamic amenorrhea (FHA), that are psychological stress, physical stress and weight loss, are associated with a decrease of the frequency of the LH secretory pulses and with a state of hypercortisolism. The slowing down of the LH pulse frequency is difficult to demonstrate in clinical practice. The classical symptoms of FHA which are low gonadotropin levels, and hypogonadism are not very specific. The diagnosis of FHA is therefore one of exclusion. Recent physiopathological studies have individualised new symptoms that are hypercortisolism, hypoprolactinaemia and an important increase in the night serum levels of melatonine, all of which could help to confirm the diagnosis. FHA is relatively frequent and its treatment with pulsatile GnRH administration or naltrexone is very successful. PMID- 8514992 TI - [Umbilical endometriosis. 2 case reports]. AB - The authors report two cases of umbilical endometriosis. Clinical diagnosis is established on menstrual rhythmicity of pain, swelling and bloody discharge. The treatment of choice for umbilical endometriosis is the surgical removal. PMID- 8514993 TI - [Inguinal hernia and endometriosis]. AB - Endometriosis is an ubiquitary disease. It can be intra or extragenital. We report the case of a patient with an endometriosic nodule at the end of an inguinal hernia, there was no other sign. The diagnosis was done through pathology. The treatment, exclusively surgical was the cure of the hernia and the excision of the nodule. PMID- 8514994 TI - [Lower urinary tract infections in women. Recent data]. AB - Lower urinary tract infection (LUTI) is a common disease of young women. It usually has a favourable prognosis, but it must not be neglected in view of its frequent recurrences and of the important morbidity it creates leading to social and sexual discomfort. LUTI, therefore, must be diagnosed, and this is done essentially by bacteriological examination of midstream urine. As regards detection of asymptomatic bacteriuria, notably in pregnant or elderly women, the sensitivity of screening is distinctly enhanced by the nitrite and leucocyte esterase tests. Recent publications concerning treatment are in favour of single dose therapy. In uncomplicated urinary tract infections, single doses of antibacterial agents are as effective as the conventional 5 to 7 days administration, and they constitute the treatment of choice of LUTI. In pregnant women, this therapeutic method has the advantage of lesser toxicity and lower frequency of vaginal candidiasis. In patients with frequent recurrences of LUTI, several options are possible: low dose continuous treatment, prophylactic treatment after situations of high risk for reinfection, or self administered single dose as soon as the symptoms reappear. However, the last two methods need to be further evaluated by additional clinical trials. PMID- 8514995 TI - [Urogenital lesions and fistulas. What's going on in Tunisia?]. AB - The authors report a series of 22 cases of post-obstetrical genito-urinary lesions. In addition, they analyse the cases of 12 patients suffering of vesico vaginal fistulae (9) or uretero-vaginal fistulae (3). They point out evident regression of these fistulae in this country which become of simple type and also emphasize on preventive measures which should be taken to reduce even more its frequency. PMID- 8514996 TI - [Chlamydia trachomatis: risk factors in women in the Parisian region. Importance of smoking and cervical ectropion]. AB - A study of chlamydial infection and its clinical correlates was undertaken collaboratively among french women attending sexually transmitted disease (STD, prenatal, and teen clinics (n = 148). A complete sexual and gynecologic history and pelvic exam was performed on all women. Endocervical and urethral cultures were obtained for C. trachomatis and N. gonorrhoeae. Reason for visit included suspected STD in 97% of STD, 5% of prenatal and 17% of teen women. N. gonorrhoeae was isolated from STD clinic patients only (17%). C. trachomatis was found in 22% of teen, 17% of STD and 2% of prenatal clinic women. C. trachomatis was significantly associated with smoking, a history of urethral discharge in the male partner, and endocervical ectopy > 50% of total cervical surface. PMID- 8514997 TI - [Amniocentesis to study the fetal karyotype before 16 weeks of amenorrhea. Prospective study comparing it with conventional amniocentesis]. AB - In a prospective study, we compared early amniocentesis (13-15 weeks of amenorrhea, n = 67) with conventional amniocentesis (16-20 weeks, n = 105). Early amniocentesis was not associated with complications and cell culture was possible in every case. Sampling failures were more frequent (4.5% vs 0.9%, p = 0.057), but had no deleterious effects and this rate can probably be reduced with experience. The mean time required for karyotyping was only slightly longer: 17.0 (SD 2.8) days vs 15.8 (SD 2.0) days (p < 0.01). These results agree with other recent studies suggesting that early amniocentesis is a simple and safe method which can be performed several weeks before conventional amniocentesis. PMID- 8514998 TI - [Evaluation of umbilical Doppler parameters in relation to placental morphology in the third trimester of normal pregnancy]. AB - The purpose of this study was to find out whether there was a relationship between placental morphology and velocimetric measurements of the umbilico placental circulation. The Doppler parameters measured at the placental insertion of the umbilical artery between 28 and 40 weeks in 145 normal pregnancies were analysed in relation to placental maturation, as evaluated by real-time ultrasonography. A significant relationship between gestational age and fetal measurements was observed in relation to the ultrasonographic progress of placental maturity. As the placental grading changed from immature to mature, no variations in Doppler parameters and placental thickness were noted. It is concluded that anatomical placental changes evaluated by ultrasonography do not correlated with the changes observed in Doppler parameters during the third trimester of normal pregnancies. PMID- 8514999 TI - [Benckiser's hemorrhage. 2 case reports and a review of the literature]. AB - Benckiser's haemorrhage is a pure foetal bleeding due to rupture of one or several umbilical vessels located within the presentation area and usually associated with velamentous insertion of the cord. The frequency of this accident has been estimated at 1:2000 to 1:5000 deliveries. The clinical picture consists of haemorrhage occurring during rupture of the membranes and rapid foetal suffering responsible for foetal death from acute exsanguination in 75 to 100% of the cases. The maternal prognosis is excellent. Since the first clinical description, in 1801, less than 200 cases have been published. Many atypical forms delaying the diagnosis have been noted. The authors report 2 lethal cases with misleading clinical presentations. With intact membranes, prevention rests on the diagnosis of vasa praevia made by vaginal palpation, amnioscopy or even ultrasonography combined with colour-coded doppler velocimetry. With ruptured membranes, the diagnosis is usually retrospective and bases on examination of the secundines. Testing foetal haemoglobin in the vaginal blood can be very useful in the absence of acute foetal suffering. The management of this haemorrhage is discussed. PMID- 8515000 TI - [Fever during labor. Evaluation of the risk of maternal-fetal infection and reflections concerning prophylactic measures based on a prospective study of 6,305 deliveries]. AB - The authors have evaluated the risk of neonatal infection (NNI) by materno-fetal contamination when a rise in temperature occurs in labour and they have worked out the prophylactic measures that should be taken. This has been the results of a prospective study carried out on 6305 deliveries. Any significant conditions associated with NNI are stained liquor and a low Apgar score at birth. When high temperature develops in labour it is important to deliver the infant as quickly as possible particularly if the labour is a premature one. Prevention carried out by very early diagnosis of amniotic fluid infection in pregnancy and by careful attention to the high risk conditions of: early rupture of the membranes, a high level of vaginal infection particularly with Beta streptococci. PMID- 8515001 TI - [The vaginal cesarean, a necessary review]. AB - Having carried out four cases of vaginal caesarean section the authors describe the technique they used. The advantages of the operation are: it is simple and can be carried out quickly, future obstetric behaviour is not compromised. It is important to avoid two complications of the operation: haemorrhage and injury to the bladder. These are reduced if the vertical incision in the cervix is made in the midline and long enough. The ideal indications for the operation are absence of cervical dilatation, or the occurrence of severe maternal haemorrhage during the operation to terminate a pregnancy, or while the uterine contents are being expelled towards the end of the second trimester. It is disputable whether there is a place for vaginal caesarean operation when the fetus is alive, in view of the recent studies on fetal prognosis. PMID- 8515002 TI - [International Federation of Gynecology and Obstetrics (FIGO). The President's bulletin]. PMID- 8515003 TI - Presidential address: physician accountability--winning the public trust. PMID- 8515004 TI - Open hand fractures: an analysis of the recovery of active motion and of complications. AB - Seventy-five of 104 patients who underwent operative fixation of open hand fractures were reviewed between 6 months and 7 years after injury (average, 17 months). There were 140 fractures involving 125 fingers. Results, evaluated on the basis of total active range of digital motion achieved at final follow-up, correlated highly with severity of soft tissue injury. When open fractures of comparable severity were contrasted between groups that did and did not require additional extension by incision to achieve acceptable reduction and stabilization, there was some additional loss of active range of motion in the surgically treated group. Metacarpal fractures had significantly better outcomes than phalangeal fractures. Fractures involving the proximal phalanx or the proximal interphalangeal joint had the poorest prognosis, especially when they were associated with tendon injury. There were significant complications in 13 fingers. Infection and late amputation were related to wound severity. PMID- 8515005 TI - Total collateral ligament excision for contractures of the proximal interphalangeal joint. AB - The complete excision of scarred proximal interphalangeal collateral ligaments as the cornerstone of surgical treatment for proximal interphalangeal joint contractures was evaluated. Supplemental palmar plate distal release, extensor tenolysis, and flexor sheath release were performed as needed. Sixteen patients with primary proximal interphalangeal joint contractures treated by this method were reviewed with the use of preoperative data obtained from chart review and postoperative data from direct patient examination. The average range of motion increased from 38 degrees to 78 degrees. No patients had instability of the proximal interphalangeal joints on manual testing and x-ray examination. This radical surgical approach to contracted proximal interphalangeal joints is justified by the improved range of motion without instability. PMID- 8515006 TI - Tendon excursions after flexor tendon repair in zone. II: Results with a new controlled-motion program. AB - Metal markers were used to study flexor digitorum profundus tendon excursions during early controlled motion with a new program combining dynamic traction and passive flexion to all four digits. The mean excursion was 2.3 mm along the middle phalanx and 11.7 mm along the proximal phalanx. This was more than twice the mean size of excursions previously achieved with a modified traditional Kleinert traction program. The mean excursion per 10 degrees of combined distal and proximal interphalangeal controlled joint motion amounted to 73% of the corresponding excursion recorded during active motion. Taken together with the findings of our previous study on tendon excursions, the results also indicate that the magnitude of excursions induced by both the distal and the proximal interphalangeal joints during controlled motion has a significant effect on adhesion formation and clinical results. However, in the region of 6 to 9 mm there appears to be a threshold beyond which the effect of a further increase in excursions becomes insignificant. PMID- 8515007 TI - Measurement of range of motion of the finger after flexor tendon repair in zone II of the hand. AB - The purpose of this study was to compare classification systems of active range of motion of the finger after flexor tendon surgery in zone II of the hand. Active range of motion of 20 fingers (16 subjects) was classified according to five systems. Agreement between the systems was only fair. Strickland's original system and the Louisville system rated the results most strictly, followed by Strickland's adjusted system. Buck-Gramcko's systems (in centimeters and degrees) rated the results least strictly. Strickland's systems conformed most closely to measurement principles. This article concludes that at this time Strickland's original classification system is preferable for scientific and clinical purposes. However, additional research is needed to evaluate reliability of the measurement, the variability of the scaling factor of 175 degrees, the sensitivity of the measurement, and the validity of the measurement with regard to functional use of the finger and gliding of the repaired tendon. PMID- 8515008 TI - The nerve gap dilemma: a comparison of nerves repaired end to end under tension with nerve grafts in a primate model. AB - The objective of this study was to compare, in a clinically relevant primate model, axon regeneration after epineurial repair under tension (15 mm gap) with interfascicular nerve grafts with the use of either standard microsuture techniques or a new interfascicular nerve graft technique termed fascicular tubulization that uses a hypoantigenic collagen membrane formed into a tube to approximate nerve ends. Electrophysiologic analysis demonstrated that the percentage of proximal axons that conducted across the repair site was greater in those nerves repaired under tension with epineurially placed sutures than in either of the tensionless repairs involving interfascicular graft techniques. The mean diameters of the regenerated axons repaired under tension with epineurial sutures were greater than those of the nerves repaired with interfascicular grafts, although the difference was not statistically significant. Interfascicular nerve grafting with tubulization using the current collagen tube resulted in regeneration equal to the sutured interfascicular nerve grafts. For modest defects (perhaps up to 3 to 4 cm in the adult), it seems advantageous to accept the modest tension associated with an epineurial repair rather than to use an autograft (or artificial graft) to achieve a tension-free repair. PMID- 8515009 TI - Peripheral nerve repair in the hand with and without motor sensory differentiation. AB - To investigate the value of motor sensory differentiated nerve repair, we examined a group of 9 patients with motor sensory differentiated nerve repair and a group of 13 patients without motor sensory differentiated nerve repair. The clinical and electroneurographic findings were compared. For the clinical examination, Millesi's scoring system was used. The hand function after motor sensory differentiated median nerve repair was 72% +/- 16% compared with 57% +/- 14% without motor sensory differentiation. The hand function after motor sensory differentiated median and ulnar nerve repair was 53% +/- 12% compared with 43% +/ 24% without motor sensory differentiation. After ulnar nerve repair the achieved values for hand function were high even without motor sensory differentiation. Our results indicate that intraoperative motor sensory differentiation of injured nerves is helpful to reestablish particularly the sensory function in median nerve injuries. PMID- 8515010 TI - The extrinsic blood supply of the ulnar nerve at the elbow: an anatomic study. AB - The extrinsic vasculature of the ulnar nerve as it relates to the treatment of cubital tunnel syndrome has not previously been described in detail. For a study of the anatomy, 18 fresh-frozen cadaver upper limbs were dissected after intra arterial injection of latex. Two major pedicles were present in all 18 specimens- the superior ulnar collateral artery proximally and the posterior ulnar recurrent artery distally. A single minor pedicle, the inferior ulnar collateral artery, was present in 5 of 18 specimens. Total vessel length as well as distance to the medial epicondyle for the extrinsic arteries was measured. On the basis of these anatomic dissections, it is suggested that the extrinsic vascular supply can be preserved during anterior transposition of the ulnar nerve, even after extensive mobilization of the nerve. PMID- 8515011 TI - Distal forearm regional block anesthesia for carpal tunnel release. AB - A technique of nerve block in the distal forearm is described for use in carpal tunnel release operations. In 70 operations, the extremities of 52 patients have been successfully anesthetized in this manner without complication. This simple anesthetic technique is recommended for use by the hand surgeon. PMID- 8515012 TI - Pseudo-anterior interosseous nerve syndrome: a case report. PMID- 8515013 TI - Anatomic relationships of an endoscopic carpal tunnel device to surrounding structures. AB - Anatomic relationships of an endoscopic carpal tunnel device to surrounding soft tissue structures along the ring finger and the long-ring interspace axis were investigated in 28 adult cadaver hands. The average distance from the center of the device to the median nerve in the carpal tunnel averaged 3.3 mm in the ring finger axis and 2.5 mm in the long-ring interspace axis. The average distance from the distal edge of the transverse carpal ligament to the superficial palmar arch was 4.8 mm in the ring finger axis and 5.5 mm in the long-ring interspace axis. These and other more subtle anatomic observations indicate the greater safety of using the ring finger axis for endoscopic carpal tunnel release. PMID- 8515014 TI - Endoscopic carpal tunnel release in a community-based series. AB - A retrospective analysis of 61 endoscopic carpal tunnel releases was performed. The surgical technique adhered strictly to the Inside Job protocol, as recommended between August and October of 1990. The objective was to provide a baseline for expected results and complications in a community practice setting. Results were rated excellent in 37 cases, good in 11, and poor in 4. Nine patients were not available for follow-up. Decreased postoperative morbidity and a more rapid return to work were found with endoscopic carpal tunnel release. The contribution of pillar pain, scar tenderness, pinch and grip weakness, and persistent numbness to good and poor outcomes were analyzed. One patient required repair of the median nerve. Another patient underwent conventional carpal tunnel release 1 year after the endoscopic procedure. Endoscopic carpal tunnel release promises to reduce morbidity. The results do not justify continued use of the Inside Job device described when conventional release is used as the standard for comparison. PMID- 8515015 TI - Acute exacerbation of carpal tunnel syndrome after radial artery cannulation. AB - Acute carpal tunnel syndrome that follows radial artery cannulation has been described. To determine the incidence and predisposing factors, we prospectively studied 151 patients who had perioperative radial artery cannulation. Postoperatively 9 of the 151 patients had symptoms of carpal tunnel syndrome with positive Phalen and Tinel signs on the side on which the radial artery catheter had been inserted. Eight of 12 patients with a prior history of carpal tunnel syndrome had acute exacerbation of symptoms postoperatively. By contrast, only 1 of 139 patients with no prior history of the disorder had symptoms. Fourteen patients had multiple arterial artery punctures or perforations of the posterior wall of the radial artery. In three of these, postoperative symptoms of carpal tunnel syndrome developed but did not reach statistical significance. The only patient with postoperative acute carpal tunnel syndrome but no prior history of the syndrome had multiple arterial punctures. The use of perioperative anticoagulation, the use of wrist-extension splints, and the duration of radial artery cannulation did not influence acute exacerbation of carpal tunnel syndrome. Patients with a prior history of carpal tunnel syndrome are at increased risk of recurrent symptoms after radial artery cannulation. We found no statistically significant relationship between traumatic cannulations and the development of symptoms of carpal tunnel syndrome. PMID- 8515016 TI - Cubital tunnel syndrome in a child with hemophilia. PMID- 8515017 TI - Early ulnar nerve palsy after radial head resection: a case report. PMID- 8515018 TI - Wrist anatomy: incidence, distribution, and correlation of anatomic variations, tears, and arthrosis. AB - We dissected 393 wrists to evaluate the incidence and distribution of anatomic features, arthrosis, chondromalacia, and soft tissue lesions. The data were then analyzed for any statistically significant associations among the different variables. The most common (73%) lunate morphology had a separate medial facet on its distal surface for the hamate. The capitate had a separate facet for the fourth metacarpal in 86% of the wrists. Fourth metacarpals with a dorsal radial facet, either separate from or connected to the rest of the fourth metacarpal base, were the most common types of fourth metacarpal. Cartilage erosion with exposed subchondral bone was identified in 58% of the wrists. It was most commonly at the proximal pole of the hamate (28%). Tears of the ligaments and/or the triangular fibrocartilage complex were identified in 56% of the wrists. The triangular fibrocartilage complex was found torn in 36% of the wrists. The lunotriquetral interosseous ligament was torn in 36% of the wrists, and the scapholunate interosseous ligament was torn in 28% of the wrists. There was a communication between the proximal wrist joint and the pisotriquetral joint in 88% of the 76 wrists, which were further dissected to assess this issue. Statistical analysis of the data found a significant correlation between the presence of cartilage erosion at the proximal pole of the hamate and the presence of a lunate facet. There was also a significant correlation between the presence of a tear in the scapholunate interosseous ligament and the presence of cartilage erosion in the scaphoid-trapezium-trapezoid joint. Analysis of the paired wrists from 169 cadavers revealed that the same soft tissue tear or combination of tears was present bilaterally in 39% of the pairs. Cartilage erosion was present bilaterally in the same location or locations in 27% of the pairs. PMID- 8515019 TI - A special plate for arthrodesis of the wrist: design considerations and biomechanical testing. AB - The purpose of this investigation was to determine the strength and mode of failure of a plate specifically designed for wrist arthrodesis. An eight-hole plate was constructed with a solid central portion and a distal taper. Four 2.7 mm screws were used in the distal (metacarpal) portion of the plate. Four 3.5 mm screws were used in the proximal (radius) portion. The strength of the wrist arthrodesis plate was compared with that of a conventional 10-hole 3.5 dynamic compression plate by gap testing and a paired cadaver wrist arthrodesis construct. The strength of the wrist arthrodesis plate was similar to the strength of the conventional dynamic compression plate when applied to cadaver wrist arthrodesis constructs. Failure of the wrist arthrodesis constructs occurred through bone without deformation of either plate. PMID- 8515020 TI - An anatomic study of the innervation of the wrist joint and Wilhelm's technique for denervation. AB - Innervation of the wrist joint has been clarified in this study by loupe dissection and histologic examination. The posterior interosseous nerve, the lateral antebrachial cutaneous nerve, the superficial branch of the radial nerve, and the dorsal branch and the perforating branches of the ulnar nerve innervate the wrist joint from the dorsal side. The anterior interosseous nerve, the palmar cutaneous branch of the median nerve, and the deep branch and the main trunk of the ulnar nerve innervate it from the palmar side. The findings indicate that surgical denervation of most of the articular nerves of the wrist joint is possible with the use of Wilhelm's procedure, but denervation of the palmar side of the intercarpal and carpometacarpal joints, which are innervated by the deep branch of the ulnar nerve, is not included in Wilhelm's technique. PMID- 8515021 TI - Osteochondral fracture in the distal end of the radius. PMID- 8515022 TI - Effects of radial deformity on distal radioulnar joint mechanics. AB - A cadaver experiment was performed to study the effects of radial deformity on the kinematics of the distal radioulnar joint and the anatomic configuration of the triangular fibrocartilage. Radial shortening caused the greatest disturbance in kinematics and the most distortion of the triangular fibrocartilage. Decreased radial inclination and dorsal angulation caused intermediate changes. Dorsal displacement produced minimal changes. Radial deformity did not produce distal radioulnar joint dislocation. These results provide biomechanical evidence of an important relationship between radial malunion and persistent symptoms in the distal radioulnar joint. PMID- 8515023 TI - Preoperative evaluation of giant cell tumors of the radius with magnetic resonance angiography. AB - We report three clinical cases of giant cell tumor of the distal radius in which reconstructions were performed with vascularized fibular grafts. Magnetic resonance angiography, a newer and noninvasive technique, was used in addition to preoperative magnetic resonance imaging. All patients had routine digital subtraction arteriography, with which magnetic resonance angiography compared favorably, demonstrating the carpal arch anatomy and other major vessels at the tumor site. In two patients the trifurcation vessels of both legs were also studied with magnetic resonance angiography before fibular harvest. In one case, the fibula graft was successfully harvested on the basis of the magnetic resonance angiographic findings. In the other case, digital subtraction arteriography had been done to evaluate suspected peripheral vascular disease. In that case magnetic resonance angiography correlated well with the digital subtraction arteriographic study, showing bilateral anterior tibial artery occlusions and patent posterior tibial and peroneal arteries. Magnetic resonance angiography has the potential to replace conventional angiography in preoperative evaluation of upper-extremity tumors. PMID- 8515024 TI - Motion after metacarpophalangeal joint reconstruction in rheumatoid disease. AB - The outcome of reconstruction of the rheumatoid metacarpophalangeal joint may deteriorate with time, especially with respect to active motion. This study assesses active finger motion after crossed intrinsic transfer and Swanson implant arthroplasty at increasing durations of follow-up to determine the effect of time. In a total of 58 patients, 21 hands had the crossed intrinsic transfer operation and 49 had the arthroplasty. Follow-up time averaged 6 years for the crossed intrinsic transfers and 21 months for the arthroplasties. Measurement of metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joint active motion at each follow-up interval were analyzed by the univariate repeated measures analysis of variance method. After crossed intrinsic transfer the overall average active range of motion decreased significantly (18 degrees) at the metacarpophalangeal joint. Proximal interphalangeal and distal interphalangeal average range of motion significantly increased during the first 5 years as a result of increases in flexion. After implant arthroplasty, the overall average metacarpophalangeal range of motion analysis at the different follow-up intervals showed that the metacarpophalangeal average range of motion significantly increased during the first 2 years and then gradually declined through the duration of follow-up. Active proximal interphalangeal flexion was also significantly increased during the first 2 postoperative years. The effects of metacarpophalangeal joint reconstruction on active finger joint motion are related to the duration of postoperative follow-up; this concept should be considered when one is planning metacarpophalangeal joint reconstruction in rheumatoid patients. PMID- 8515025 TI - Avulsion fracture of the extensor carpi radialis brevis insertion. PMID- 8515026 TI - Acute flexor superficialis avulsion. PMID- 8515027 TI - First web space contracture and hand function. AB - We studied 125 normal volunteers to determine the normal first web space angle and to evaluate the influence of thumb-index finger web space contracture on hand function. One hundred ninety-five hands were measured and found to have a mean web space angle of 100 degrees. There was no significant difference in the mean angle in relation to sex or hand dominance. The mean angle was significantly smaller for persons 50 to 79 years of age than for the two younger age groups. Twenty-five normal volunteers (50 hands) took the Jebsen-Taylor test three times: first, with no restrictions; second, with splints simulating a 60-degree web space contracture; and third, with splints simulating a 30-degree contracture. More than half of the volunteers had abnormal small-object subtests. Other abnormal subtests included card turning, feeding, and stacking checkers. Grasping large light and heavy objects was less difficult because of compensatory techniques used by the volunteers. PMID- 8515028 TI - Osteomyelitis of the hand after a human bite. AB - Twenty-four cases of osteomyelitis of the hand after human bite were reviewed. The mechanism of injury was equally divided between incisor bites and clenched fists. Eleven of twelve of the clenched-fist injuries showed a tooth mark in the bone or cartilage at the site of inoculation. The incisor bites showed initial infection of the soft tissues or joint with a secondary infection of the bone. Factors leading to the development of osteomyelitis included a delay of more than 24 hours before debridement or inadequate initial treatment. Bacteriologic study commonly showed mixed infections with skin and oral flora. The infections were prone to relapse, and nine patients required more than one surgical debridement. PMID- 8515029 TI - Lionfish envenomation of the hand. AB - Lionfish (Pterois volitans) envenomation of the hand causes excruciating pain and occurs in three grades: (1) erythematous reaction, (2) blister formation, and (3) dermal necrosis. The initial treatment in all cases is to soak the hand in nonscalding water (45 degrees C) until the pain subsides by denaturing the thermolabile venom proteins. The blisters should be immediately excised to prevent dermal necrosis, inasmuch as the blister fluid contains residual active venom. To prevent a hypersensitivity reaction, any further contact with the fish should be avoided. PMID- 8515030 TI - The digital palmar oblique incision. AB - Although many incisions have been described for exposure of the palmar structures of the digits, all have some disadvantages. The digital palmar oblique exposure provides a direct approach to the flexor tendons in the fingers and palm and to the digital neurovascular bundles and has been used extensively at our clinic for more than 20 years. Flap tip necrosis, central migration of the incision, scar hypertrophy, and flexion contractures have not been problems with the use of this incision. PMID- 8515031 TI - A reversed digital artery island flap for the treatment of fingertip injuries. AB - A series of complex fingertip injuries managed with a reversed digital artery island flap is presented. An island of skin on the side of the proximal phalanx can be elevated on a digital arterial pedicle and rotated to the fingertip to provide abundant skin and subcutaneous coverage for acute or chronic deficits. The flap receives retrograde flow from its ipsilateral digital artery after passage through dorsal and palmar vascular plexuses at the middle and distal phalangeal level. Thirteen flaps were performed on eleven patients with no loss of any portion of the flap. The advantages of this procedure include a reconstruction that necessitates surgery only on the injured digit, allowing for the treatment of single or multiple fingertip injuries that provides functional sensation in the reconstructed fingertip without causing loss of motion. PMID- 8515032 TI - Transfer of innervated latissimus dorsi free musculocutaneous flap for the restoration of finger flexion. AB - Transfer of functioning free muscle for the restoration of finger flexion is an uncommon procedure. We present our experience with five patients with severe forearm injuries in whom a latissimus dorsi musculocutaneous free tissue transfer was performed in an attempt to provide soft tissue coverage and active digital flexion. Four patients had active finger flexion with volitional control of the transferred muscle between the tenth and the fifteenth weeks. On average, active flexion lags were 2.0 cm in the index finger, 2.1 cm in the long finger, 2.3 cm in the ring finger, and 1.4 cm in the small finger. Although preoperative grip strength was doubled, postoperative strength was still only about 31% of that on the opposite side. All patients required at least one tenomyolysis or revision tenorrhaphy before the best clinical outcome was achieved. PMID- 8515033 TI - Writer's cramp--a focal dystonia: etiology, diagnosis, and treatment. AB - The complaint of hand cramps is common among patients who consult the neurologist or the hand surgeon. Classic writer's cramp is best characterized as a focal dystonia, and electromyographic studies reveal a characteristic pattern of cocontraction of the agonist and antagonist muscles of the forearm and hand. Although the outcome of treatment in the past has been unsatisfying, recent experience with new pharmacologic therapy, such as injections of botulinum toxin, has produced promising results. Further experience and improvement in this area will likely increase the therapeutic success in the treatment of writer's cramp and other focal dystonias. PMID- 8515034 TI - Open reduction and internal fixation for distal radial fractures. PMID- 8515035 TI - Injection injuries to the median and ulnar nerves of the wrist. PMID- 8515036 TI - Is it possible to call a "tear" on arthrograms or magnetic resonance imaging scans? PMID- 8515037 TI - Needed: physician volunteers to care for indigent. PMID- 8515038 TI - Are you volunteered out? PMID- 8515039 TI - Assisted suicide is 'bad for medicine'. Interview by Bob Carlson. PMID- 8515040 TI - Volunteer health care in Indiana. PMID- 8515041 TI - Physician volunteers 'give back to community'. Interview by Tina Sims. PMID- 8515042 TI - Premenarchal vulvovaginitis. PMID- 8515043 TI - From the museum. PMID- 8515044 TI - Cytoskeletal structure of skeletal muscle: identification of an intricate exosarcomeric microtubule lattice in slow- and fast-twitch muscle fibers. AB - We used immunochemical quantification and indirect immunofluorescence to investigate the cell content, distribution, and organization of microtubules in adult rat slow-twitch soleus and fast-twitch vastus lateralis muscles. An immunoblotting assay demonstrated that the soleus muscle (primarily Type I fibers) was found to have a 1.7-fold higher relative content of alpha-tubulin compared with the superficial portion of the vastus lateralis muscle (primarily Type IIb fibers). Both physiological muscle types revealed a complex arrangement of microtubules which displayed oblique, longitudinal, and transverse orientations within the sarcoplasmic space. The predominance of any one particular orientation varied significantly from one muscle tissue section to another. Nuclei were completely surrounded by a dense net-like structure of microtubules. Both muscle fiber types were found to possess a higher density of microtubules in the subsarcolemmal region. These microtubules followed the contour of the sarcolemma in slightly contracted fibers and showed a fine punctate appearance indicative of a restricted distribution. The immunofluorescence results indicate that microtubules are associated with the sarcolemma and therefore may form a part of the membrane cytoskeletal domain of the muscle fiber. We conclude that the microtubule network of the adult mammalian skeletal muscle fiber constitutes a bone fide component of the exosarcomeric cytoskeletal lattice domain along with the intermediate filaments, and as such could therefore participate in the mechanical integration of the various organelles of the myofibers during the contraction-relaxation cycle. PMID- 8515045 TI - Detection of DNA fragmentation in apoptosis: application of in situ nick translation to cell culture systems and tissue sections. AB - Since DNA fragmentation is a key feature of programmed cell death (PCD) and also occurs in certain stages of necrosis, we have adapted the methodology of in situ nick-translation (ISNT) to detect DNA fragmentation on a single-cell level. We first established the technique for cell preparations. Apoptosis was induced by gamma-irradiation on freshly isolated rat thymocytes. After fixation procedures, ISNT was performed by overnight incubation either with fluorescein-12-dUTP or with digoxigenin-labeled 11-dUTP and DNA polymerase I. The enzymatic incorporation of labeled nucleotides at sites of DNA fragmentation was detected by flow cytometry either directly or indirectly with fluorescein-conjugated anti digoxigenin. The quantitative results demonstrated close correlation with morphological essays for apoptosis, DNA gel electrophoresis, and ISNT. Proliferating cells determined by bromodeoxyuridine immunofluorescence were not labeled by ISNT. Immunocytochemistry for cell surface antigens in combination with ISNT allowed the identification of specific cell types undergoing PCD. Furthermore, the simultaneous application of photolabeling techniques with ethidium monoazide and ISNT led to the identification of DNA fragmentation in cells with still intact membranes. Extending ISNT to tissue sections of paraformaldehyde-fixed, paraffin-embedded material reliably revealed labeling of cells with typical morphological features of apoptosis. However, this technique was not useful in detecting early stages of necrotic cell death. PMID- 8515046 TI - Early and late transformations occurring at organelles of the Golgi area under the influence of brefeldin A: an ultrastructural and lectin cytochemical study. AB - We investigated the early and late changes of the Golgi region under the influence of the fungal metabolite brefeldin A (BFA) by electron microscopy and lectin cytochemistry using the beta-galactose-specific lectin from the beetle Allomyrina dichotoma (Allo A). In control cells, Allo-A reactions were confined to trans-Golgi elements, the trans-Golgi network, and to endosomes and lysosomes; the nuclear envelope and endoplasmic reticulum were consistently free of Allo A reactions. Our findings with cells from three different lines (i.e., HepG2 hepatoma cells, WI38 fibroblasts, and L132 embryonic lung cells) showed tubular reticular transformations of the Golgi stacks as early as 30 sec after application of BFA. The transformations started at the cis side and proceeded rapidly; after only a few minutes the Golgi apparatus was no longer apparent as an individual entity. Simultaneously, giant tubules grew out of the Golgi region and traversed the cytoplasm over micrometer-long distances. In part, they were reactive for Allo A. Reactions for beta-galactose occurred in cisternae of the endoplasmic reticulum after 4-5 min of BFA treatment; after 30 min the entire endoplasmic reticulum was intensely reactive for Allo A. At 5 min and later, the tubular-reticular transformations appeared more compact, forming glomerulus-like structures (glomerulini). These were closely associated with cisternae of the endoplasmic reticulum. Initially, glomerulini were mostly Allo A negative or showed peripheral Allo A-positive segments. The number of Allo A-positive glomerulini increased with the duration of treatment. Our findings identify the glomerulini as bipolar structures forming a link between the endoplasmic reticulum and the dissociating Golgi stacks. PMID- 8515047 TI - Lucifer yellow filling of immunohistochemically pre-labeled neurons: a new method to characterize neuronal subpopulations. AB - We describe a new technique for the morphological characterization of immunohistochemically labeled neuron populations. We demonstrate that it is possible to fill neurons iontophoretically with Lucifer Yellow (LY) in fixed slices of cat visual cortex after the respective cells have been identified by indirect immunofluorescence for the neural cell adhesion molecule N-CAM 180, with the VC1.1 antibody or with an antibody against glutamate dehydrogenase (GAD). Morphological analysis of the injected cells at the light and electron microscopic level revealed that the N-CAM 180-positive neurons share the features of neuropeptidergic cortical interneurons. Depending on the antibody applied, the immunohistochemical treatment had little or no noticeable effect on the quality of LY filling or on the preservation of morphological details of the pre-labeled cells. This makes the method described ideally suited for the light and electron microscopic examination of selected, immunologically characterized neuron subpopulations. PMID- 8515048 TI - A histochemical approach to the mechanism of action of cisplatin and its analogues. AB - The effects of cisplatin (CDDP), a potent anti-cancer agent, and its various analogues were analyzed for any biochemical changes involving Ca2+ and lysosomal and membrane-associated transport enzymes in rat kidney, liver, serum, urine, tissue homogenates, and isolated mitochondria. Correlation was made with any morphological changes observed by light and electron microscopy to gain an insight into the mechanism of action of various platinum coordination complexes. CDDP in its hydrolyzed state under conditions of low chloride ion concentrations causes uncoupling of oxidative phosphorylation, calcium efflux from the mitochondria, inhibits ATP synthesis, lowers membrane-associated calcium and various membrane transport enzymes, and induces an increase in the number of lysosomes. Enzymes such as alkaline phosphatase are stripped from the brush borders of the proximal tubule cells and are discharged in the urine. However, daily IV injections of calcium (1.1 ml of 1.3% CaCl2) supplementation protect the membrane-associated enzymes from cisplatin action. Carboplatin (CBDCA), an analogue of CDDP and the least nephrotoxic of all its analogues, shows little effect on the membrane-associated transport enzymes. Therefore, cisplatin and its various analogues seem to affect the membrane transport enzymes to varying degrees with related nephrotoxicity. Calcium supplementation seems to protect these enzymes and preserve kidney function. PMID- 8515049 TI - Lysosomal cysteine and aspartic proteinases, acid phosphatase, and an endogenous cysteine proteinase inhibitor, cystatin-beta, in rat osteoclasts. AB - To understand the bone resorption and lysosomal proteinases in osteoclasts, we examined by immunohistochemistry the localization of lysosomal cysteine and aspartic proteinases, acid phosphatase, and cystatin-beta in the rat tibial bone. Immunoreactivity for cathepsins B, C, H, and L, cathepsin D, acid phosphatase, and cystatin-beta was demonstrated in various cells of the bone tissue; in particular, large multinucleated osteoclasts attached to the bone surface and chondroclasts in the proximal growth plate. These cells showed intense immunoreactivity for these lysosomal enzymes and cystatin-beta. Bone surface lining osteoblasts displayed distinct immunoreactivity for cathepsins B, C, D, H, and acid phosphatase, while osteocytes often exhibited that for cathepsins D, H and acid phosphatase. Chondrocytes in the growth plate demonstrated intense immunoreactivity for cathepsins B, D, and acid phosphatase. Immunoreactivity for cystatin-beta was detected in osteoclasts and chondroclasts only. Large, round multinucleated cells free from the bone surface exhibited weak, faint, or no immunoreactivity for the lysosomal enzymes and cystatin-beta. These results suggest that lysosomal cysteine and aspartic proteinases may play a role in the degradation of organic constituents of the bone matrix. Moreover, cystatin-beta can serve as an excellent marker protein for osteoclasts. PMID- 8515050 TI - Label-fracture of plasma membranes isolated from measles virus-infected cells. AB - We present a method that permits correlation of the intramembrane architecture of plasma membrane fracture faces with the distribution of specific molecules at the corresponding cytoplasmic or exoplasmic membrane surfaces. HeLa cells infected with measles virus were used as a model system. Large fragments of the dorsal membrane were isolated after the virus glycoproteins were tagged at the outer cell surface with immune serum and protein A-gold markers. In a second step, different virus polypeptides at the inner cell surface were also identified by a smaller gold label. Thereafter, the isolated plasma membranes were frozen and freeze-fractured. The complementary fracture faces were shadowed with heavy metals and carbon and examined in the transmission electron microscope without cleaning of remaining biological material. Thus, the micromorphology of the replicated fracture faces and the topochemistry of virus components localized at the corresponding leaflets of the plasmalemma could be seen on the same image at high resolution. Of note is that the freeze-fracture morphology of the protoplasmic face is related to the molecular composition of the cytoplasmic surface, as revealed by antibody tagging. PMID- 8515051 TI - Localization of S1 and elongation factor-1 alpha mRNA in rat brain and liver by non-radioactive in situ hybridization. AB - Elongation factor-1 alpha (EF-1 alpha) is a ubiquitous, highly conserved protein that functions in peptide elongation during mRNA translation. We recently reported that, as do lower species, mammals also contain a second EF-1 alpha-like gene (S1). Unlike EF-1 alpha, which is present in all tissues, S1 mRNA is detected only in brain, heart, and muscle by Northern analysis and RNAse protection assays. In this report we present the identification of S1 and EF-1 alpha messages by non-radioactive in situ hybridization in brain and liver. We show that with this technique we can detected S1 mRNA only in certain cells in brain, mostly neurons; on the other hand, EF-1 alpha is present in all cell types that we have studied so far. We demonstrate that although EF-1 alpha mRNA can be detected in S1-negative cells it is also present in high abundance in S1-positive cells. The results presented here correlate with our previous finding that mammalian species contain a tissue-specific EF-1 alpha-like gene, S1. The presence of a second EF-1 alpha-like transcript within fully differentiated cells suggests a novel cell type-specific gene expression whose function may be related to the permanent growth-arrested state of cells in brain, heart, and muscle. PMID- 8515052 TI - Comparison of the sensitivities of ribonucleic acid and oligonucleotide probes for in situ detection of Theiler's virus mRNA. AB - To evaluate the sensitivity of in situ detection of the Theiler's virus genome, we hybridized BHK-21-infected cells with antisense ribo- and oligonucleotide 35S labeled probes. The sensitivity achieved with the anti-sense 280-nucleotide riboprobe was similar to that obtained with a 93-mer oligonucleotide probe. However, more reproducible and accurate results were obtained with the riboprobe. With long exposure times, the background was higher with the oligonucleotide probe than with the RNA probe. The background was improved by using freshly labeled oligonucleotide probe. PMID- 8515053 TI - Expression of follistatin mRNA by somatotropes and mammotropes early in the rat estrous cycle. AB - We previously found follistatin (FS) mRNA in gonadotropes [predominantly in cells with luteinizing hormone (LH) antigens] and folliculostellate cells (with S100 antigens) in diestrus rats pituitaries. However, earlier in the cycle, when percentages of gonadotropes are lowest, percentages of cells expressing FS are 1.5-2-fold higher than in diestrus. This study was designed to detect FS mRNA and other pituitary antigens to identify the additional cells with dual in situ hybridization and immunolabeling protocols. The mRNA was detected with biotinylated complementary oligonucleotide probes and avidin-biotin-peroxidase complexes. Significant labeling for FS mRNA was found in cells with the following antigens: growth hormone (GH) (7% of pituitary cells); prolactin (PRL) (5%); S100 protein (5%); follicle-stimulating hormone (FSH beta) (4%); LH beta (3%); and thyroid-stimulating hormone (TSH beta) (3%). Optimal conditions for detection included: overnight plating of > 50,000 cells/well (24-well tray) in media containing 10% fetal bovine serum; hybridization at 37 degrees C; and fixation in 2% glutaraldehyde. Whereas FS is expressed predominantly by LH gonadotropes at midcycle, FS mRNA can be expressed by all types of antigen-bearing cells earlier in the cycle. Its function in the pituitary may relate to its role in binding activin, which would result in inhibition of FSH release. However, since activin inhibits secretion of GH, PRL, and adrenocorticotropin (ACTH), FS may also control activin's effects on these cells. The FS-expressing cells may therefore be paracrine or autocrine regulators. PMID- 8515054 TI - Effects of digitonin on the intracellular content of rat hepatocytes: implications for its use in the study of intralobular heterogeneity. AB - Anterograde or retrograde perfusion of rat liver with digitonin selectively permeabilizes the periportal or the perivenous zone of the hepatic lobule. Digitonin perfusion is used to analyze the effluents released by permeabilized hepatocytes or, combined with collagenase perfusion, to obtain cell suspensions enriched in either periportal or perivenous hepatocytes. Despite the wide use of digitonin to study lobular heterogeneity, its affects on rat hepatocytes are not well documented. We therefore analyzed the effects of digitonin perfusion on the intracellular content of rat hepatocytes by combining electron microscopy, histoenzymology, immunohistochemistry, and in situ hybridization. At the concentration currently used for the study of lobular heterogeneity, digitonin perfusion induced a marked cytosolic clarification of permeabilized hepatocytes, while most organelles except mitochondria were well preserved. In the digitonin altered zones, there was no histochemical detection of non-membrane-bound enzymes (lactate dehydrogenase, glutamate dehydrogenase), whereas membrane-bound enzymes (succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, NADPH dehydrogenase, glucose-6-phosphatase) were still detected. Immunohistochemistry and in situ hybridization revealed significant amounts of several plasma proteins (albumin, alpha 2-macroglobulin, alpha 1-inhibitor 3, alpha 1-acid glycoprotein) and their respective mRNAs in digitonin-permeabilized hepatocytes. The demonstration that digitonin-permeabilized hepatocytes retain many intracellular constituents shows that biochemical analysis of cellular effluents released from digitonin-permeabilized hepatocytes must be interpreted with caution and that the apparent characteristics of cell suspensions obtained by the digitonin collagenase technique might be significantly altered by contamination with permeabilized hepatocytes from the opposite zone. PMID- 8515055 TI - Phenotypic and functional characterization of T cell lines specific for individual respiratory syncytial virus proteins. AB - Mice sensitized to individual respiratory syncytial (RS) virus proteins show distinct patterns of immunity and pulmonary pathology when challenged with live virus. To explore the immune mechanisms responsible for the differences in postvaccination disease, BALB/c (H-2d) mice were primed by scarification with recombinant vaccinia viruses (rVV) expressing the major glycoprotein (G), fusion protein (F), phosphoprotein (P), nucleoprotein (N), or second matrix (22K) protein of RS virus. Ag-stimulated spleen cell cultures gave rise to CD3+TCR alpha beta + T cell lines. Those from rVV-F-primed mice contained a mixture of CD8+ and CD4+ T cells, whereas those specific to G, N, and P were mostly CD4+. In contrast, 22K-specific lines were mostly CD8+. F- and 22K-specific lines showed virus-specific CTL activity against H-2d targets, but the lines from rVV-G-, -N-, and -P-primed mice did not. The F-specific lines contained Th cells that released an excess of IL-2 and some IL-3 but little IL-4 or IL-5 (i.e., a "Th1" pattern). In contrast, the G-specific line released IL-3, IL-4, and IL-5 but little IL-2 (i.e., a "Th2" pattern). The 22K line contained IL-3-releasing T cells. Staining of T cell subsets for CD45RB varied in intensity in different lines, consistent with the cytokine secretion profiles of the Th cells that they contained. Because different RS virus proteins (given in the same form by the same route) prime for functionally different T cells, the ways in which individual proteins are processed and presented might be important in determining these patterns of immunity. PMID- 8515056 TI - Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. AB - Normal aging in humans has been recently shown to be accompanied by reduced control over production of the multifunctional cytokine IL-6. This cytokine was reported to be quantitatively elevated in most serum samples obtained from "normal" elderly humans. In the present investigation, we report that IL-6 levels are elevated in serum samples obtained from aged mice, and its spontaneous production could also be easily detected in culture supernatants of unstimulated lymphoid cells obtained from aged, but not mature, adult donors. Spontaneous production of IL-6 was consistently observed in culture supernatants of lymphoid cells from both the spleen and mesenteric lymph nodes from aged donors, but was absent from supernatants derived from their peripheral lymph nodes. In aged mice, the reduced regulation of IL-6 production could be effectively prevented and/or reversed by supplementing aging animals with dehydroepiandrosterone sulfate, a steroid hormone whose endogenous production is known to decline with advancing age in all species tested. It was also established that serum obtained from old dehydroepiandrosterone sulfate-treated mice contained lower (normal) levels of serum amyloid P substance (an acute phase reactant), reduced levels of serum Ig (all classes and isotypes) and lower titers of tissue-specific autoantibodies than untreated aged controls. Therefore, a number of well described, age-related conditions, some of which could be contributing to the pathologic phenotype of old age, may actually represent secondary effects to this age-associated change in IL-6 production. PMID- 8515057 TI - Identification of functional domains in murine granulocyte-macrophage colony stimulating factor using monoclonal antibodies to synthetic peptides. AB - Granulocyte-macrophage (GM)-CSF is an important hematopoietic cytokine that regulates proliferation and differentiation of macrophages, neutrophils, and eosinophils. In this study, we generated mAb to five synthetic peptides that correspond to regions along the murine GM-CSF molecule. The ability of anti peptide mAb to bind to and inhibit biologic activity of murine (m) GM-CSF was determined. mAb with the highest neutralization titers were derived from mice immunized with peptide II, which correspond to amino acids 27 to 38 of mGM-CSF. Immunochemical studies showed that peptide II specifically blocked binding of anti-peptide II mAb to GM-CSF. mAb to two other peptides in the N-terminal half corresponding to residues 7 to 17 and 47 to 58, respectively, of mGM-CSF also inhibited GM-CSF-dependent proliferation and differentiation of murine bone marrow precursors for macrophages and granulocytes. Anti-peptide mAb also inhibited growth of a murine hematopoietic cell line FDCP1 and a murine T cell line HT-2, which was shown to be dependent on GM-CSF for growth in vitro. Biologic activity of both natural and recombinant mGM-CSF was neutralized by anti peptide mAb. These findings indicate that epitopes in the N-terminal region of mGM-CSF are important for biologic activity, and the epitope defined by peptide II (residues 27 to 38) lies within a particularly important functional domain of the mGM-CSF molecule. PMID- 8515058 TI - Characterization of a novel cell-surface molecule expressed on subpopulations of activated T and B cells. AB - A mAb, GL7, is described that reacts with a 35-kDa protein on subsets of activated mouse B cells as well as activated CD4+ and CD8+ peripheral T cells. In normal mice analyzed by flow cytometry, GL7 bound at low surface density to 0 to 9% of splenic B cells and 0 to 1% of splenic T cells. In contrast, GL7 bound at high density to a subpopulation comprising approximately 20% of TCR-bright thymocytes, and to B220+ cells in the bone marrow. The activation of B cells by various stimuli resulted in high levels of expression of the surface molecule identified by GL7 on up to 70% of B cells after 48 h; the remaining B cells expressed low or undetectable levels of this molecule, despite evidence of other activation-specific changes in cell-surface phenotype. The GL7-positive population of B cells induced by IL-5 stimulation exhibited high levels of both proliferative and IgM secretory activity, whereas the GL7-negative population showed little of either activity. Activation of splenic T cells with Con A for 48 h resulted in the expression of this determinant at high density on both CD4+ and CD8+ cells. GL7 thus appears to identify a previously uncharacterized cell surface molecule expressed selectively on subpopulations of activated B and T cells as well as on discrete subpopulations of T and B lineage cells in vivo. PMID- 8515059 TI - Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements. AB - In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL 2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo. PMID- 8515060 TI - MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors. AB - MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4 induced proliferation. The costimulatory effect was most pronounced at low concentrations of IL-2, was blocked by IL-2R mAb, and was at least partly mediated through an up-regulation of IL-2 high affinity receptors. As expected, activation of IL-2R by IL-2 induced tyrosine phosphorylation of several proteins including p56lck, and class II cross-linking by mAb induced tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation suggesting that class II costimulation of IL-2 responses may involve activation of tyrosine kinases. Taken together, the present data suggest that extensive cross-linking of class II molecules delivers costimulatory signals that enhance IL-2 sensitivity in human T cells. PMID- 8515061 TI - T cell-macrophage cognate interaction in the activation of macrophage effector function by Th2 cells. AB - The in vitro induction of cytostatic/cytotoxic activity in macrophages generated in spleen cell cultures requires a signal cascade initiated by costimulation with both LPS and IFN-gamma. Th2 lymphocytes, although they do not produce IFN-gamma, can provide the signals necessary for induction of cytostatic activity in IFN gamma-primed macrophages. These signals appear to be delivered by cognate interaction between the Th2 cells and macrophages in that: 1) they are not delivered by culture supernatants of Th2 cells activated 6 or 20 h by Con A or by immobilized anti-CD3 mAb; 2) they are not delivered if cell contact between Th2 cells and macrophages is prevented; and 3) they can be delivered by paraformaldehyde-fixed activated Th2 cells. Paraformaldehyde-fixed resting Th2 cells cannot stimulate activation of INF-gamma-primed macrophages. The Th2 cells must be activated at least 3 h before fixation to acquire macrophage stimulatory activity. Optimal macrophage-stimulating activity is attained after 6-h activation of the Th2 and declines thereafter. Although the activation of IFN gamma-primed macrophages by viable resting Th2 displays Ag specificity and MHC restriction, the activation of IFN-gamma-primed macrophages by paraformaldehyde fixed activated Th2 is neither Ag specific nor MHC restricted. These observations suggest that T cell-mediated activation of macrophages can involve a signaling cascade of Ag-specific and Ag-nonspecific adhesion events comparable to those hypothesized to occur in T cell-mediated B cell activation. PMID- 8515062 TI - Anti-CD3-stimulated Ca2+ signal in individual human peripheral T cells. Activation correlates with a sustained increase in intracellular Ca2+1. AB - The changes in [Ca2+]i after mitogen stimulation of individual human peripheral T cells were examined by single cell image analysis to determine the relationship between the Ca2+ signal and functional outcome. Marked heterogeneity in the magnitude of increase in [Ca2+]i, in the lag time of the responses, and in the percentage of T cells that responded to mAb to CD3 and to PHA was observed. However, mitogenic stimuli that induced IL-2 production or DNA synthesis consistently generated increases in [Ca2+]i in individual T cells that were sustained for 1 to 2 h. Soluble mAb to CD3 induced an increase in [Ca2+]i that remained elevated at 60 min and led to IL-2 production and proliferation upon costimulation by phorbol ester. In contrast, cross-linking anti-CD3 with a secondary antibody foreshortened the increase in [Ca2+]i, and IL-2 production and DNA synthesis were inhibited. Immobilized anti-CD3, which can stimulate T cell proliferation and IL-2 production in the absence of phorbol ester, produced a constant sustained elevation in [Ca2+]i that lasted more than 2 h. Similarly, functional responses could be generated by concentrations of PHA that resulted in only a slow increase in [Ca2+]i that continued to rise for 1 to 2 h. Examination of the mitogen-induced sustained increases in [Ca2+]i suggested that an elevation in [Ca2+]i as small as 50 to 100 nM above control mean [Ca2+]i was associated with evidence of T cell activation. Spontaneous oscillatory changes in [Ca2+]i were observed in a small percentage of peripheral T cells although they were noted to occur frequently in Jurkat cells. Mitogenic stimulation did not consistently increase oscillations in peripheral T cells, and neither their frequency nor their magnitude correlated with IL-2 production or DNA synthesis. These observations suggest that oscillatory changes in [Ca2+]i are not a primary determinant of T cell activation. Rather, the data indicate that functional activation of T cells by PHA and anti-CD3 is correlated with the induction of a small, but sustained increase in [Ca2+]i. PMID- 8515063 TI - A common sequence motif near nonhomologous recombination breakpoints involving Ig sequences. AB - Analysis of nonhomologous recombination events at the Ig loci revealed that a four base sequence, 5'-CCAG-3', or its complement, 5'-CTGG-3', is present within seven nucleotides in 12 of the 13 examined recombination breakpoints. Statistical analysis of the data indicates that this occurrence has a probability of less than 10(-5) of occurring by chance. This sequence is infrequently found at nonhomologous recombination breakpoints in non-Ig sequences, suggesting that its contribution may be either Ig- or B cell-specific. Intriguingly, this tetranucleotide is also found to be associated with the breakpoints of VH gene replacement and isotype switching, suggesting that common pathways may be involved in all three B cell processes. PMID- 8515064 TI - Syrian and Armenian hamsters differ in serum amyloid A gene expression. Identification of novel Syrian hamster serum amyloid A subtypes. AB - Amyloid A (AA) amyloidosis is widespread throughout the animal kingdom. Several factors including: 1) precursor production; 2) precursor structure; 3) precursor degradation; and 4) precursor/product interaction with the pentraxin serum amyloid P have been implicated in amyloidogenesis, but the exact sequence of events leading to AA fibril formation and deposition remains unclear. Most models of experimental amyloidosis, including golden Syrian hamsters (Mesocricetus auratus), involve massive and repeated inflammatory stimulation; however, the model of spontaneous amyloidosis with aging in female, but not male, Syrian hamsters permits analysis of amyloidogenic factors in the absence of inflammation. Another genus, the Armenian hamster (Cricetulus migratorius), differs from Syrian hamsters both in gender-specific serum amyloid P expression and susceptibility to AA amyloidosis. In this study, we describe novel SAA molecules in the Syrian hamster in the presence and absence of inflammation. We demonstrate that, based on isoelectric separation, the Syrian hamster SAA proteins can be separated into two broad subfamilies. Plasma SAA concentration in female Syrian hamsters increases spontaneously with age, and fragments of a basic SAA isotype expressed both hepatically and extrahepatically are selectively deposited as AA fibrils. After inflammatory stimulation, the patterns of SAA gene expression in Syrian and Armenian hamsters differ. In Syrian hamsters, both hepatic SAA mRNA and the high density lipoprotein apoSAA content increase approximately 1000-fold; in Armenian hamsters, hepatic SAA mRNA is limited in quantity and different in structure; and although plasma SAA proteins increase three- to fivefold, apoSAA is not detectable in high density lipoprotein. The results suggest that regulation and site of precursor production as well as precursor structure influence AA amyloidogenesis in these two hamster genera. PMID- 8515065 TI - Simultaneous transfer of four functional genes from the HLA class II region into mammalian cells by fusion with yeast spheroplasts carrying an artificial chromosome. AB - Gene transfer using yeast artificial chromosome (YAC) clones provides an opportunity to study the expression of several linked genes within an environment more closely approximating their normal chromosomal context. A YAC clone spanning 330 kb of the HLA class II region from centromeric of TAP 1 to telomeric of HLA DQA1 was retrofitted by homologous recombination with a neomycin plasmid targeted either to an Alu repeat sequence within the YAC genomic insert or to the Ura-3 gene within the right arm of the YAC vector. The modified YAC clones were transferred to Chinese hamster ovary or L cells by spheroplast fusion. Eight of 14 Alu-retrofitted and 10 of 15 right arm-retrofitted neomycin clones retained the six human loci known to be encoded by the YAC as well as portions of the left and right YAC vector arms. All tested L cell transformants showed IFN-gamma inducible TAP 1 and TAP 2 mRNA expression. Two of eight analyzed clones expressed HLA-DQB mRNA and one of four expressed HLA-DQA. Cells expressing both the HLA-DQA and -DQB mRNA showed HLA-DQ cell surface expression. These studies establish the feasibility of introducing groups of functional genes into mammalian cells by spheroplast fusion with a single YAC clone. PMID- 8515066 TI - Characterization of two novel Ly-6 genes. Protein sequence and potential structural similarity to alpha-bungarotoxin and other neurotoxins. AB - Genomic clones cross-hybridizing with Ly-6A.2 cDNA were isolated and characterized for functional Ly-6-related genes. Two new Ly-6 genes, designated Ly-6F.1 and Ly-6G.1, were found to have high nucleotide homology (> or = 70%) and the characteristic four exon gene organization of Ly-6A/E and Ly-6C. By a PCR based assay, Ly-6G.1 mRNA was readily found in bone marrow, whereas Ly-6F.1 mRNA was not detected in lymphoid tissues. Thus, Ly-6G.1 represents an additional Ly-6 gene with apparent selective expression in hematopoietic cells distinct from Ly 6A/E and Ly-6C. Using the available deduced protein sequence data for mature Ly-6 proteins, searches of the database uncovered an evolutionary relationship of Ly-6 proteins with neurotoxins isolated from snake venoms. The protein sequence conservation between the two groups was selective for, but not limited to, residues in neurotoxins that have been found to be important for their tertiary structures. From this relationship, we propose a neurotoxin-like structure for Ly 6 and Ly-6-related proteins, such as CD59. PMID- 8515067 TI - Regulation of the expression of human C epsilon germline transcript. Identification of a novel IL-4 responsive element. AB - Transcriptional regulation for Ig H chain germline transcripts induced by cytokines is a topic of recent interest for the understanding of the mechanism of class switch recombination. Among human B cell lines examined, we have found that a human IgM-producing B cell line, DND39 (EBV negative) expressed germ-line transcripts of epsilon constant gene (C epsilon) when stimulated with IL-4. In our study, the regulatory element responsible for the expression of IL-4-induced human C epsilon germ-line transcript was determined using DND39 cells. To identify the IL-4 responsive promoter/enhancer element, deletion analysis of the upstream region of the germ-line exon (I epsilon) of the C epsilon germ-line transcript which is located 5' to the switch region, was performed by using a luciferase gene as a reporter. Deletion analysis showed that a DNA fragment which lies between -215 and -154 bp upstream from the most 3' transcriptional initiation site of human I epsilon gene is fully responsible for the induction of germ-line transcripts by IL-4. According to a mutational analysis, the DNA fragment between -163 and -152 bp, was identified to be a novel IL-4 responsive element in a human C epsilon gene. Electrophoretic gel mobility shift assay showed the presence of IL-4-induced nuclear factor that specifically bound to this IL-4 responsive element. This novel IL-4 responsive element and an IL-4 induced DNA binding protein may play an important role for the induction of C epsilon germ-line transcript as well as class switching to IgE. PMID- 8515068 TI - Variable IgH chain enhancer activity in Burkitt's lymphomas suggests an additional, direct mechanism of c-myc deregulation. AB - The deregulation of the c-myc gene in small non-cleaved cell lymphomas (SNCL) with 8;14 translocations is thought to be due to the juxtaposition of this gene with the IgH chain locus, but exactly how the Ig locus contributes to the deregulation is unclear. One widely considered hypothesis is that Ig gene enhancers, when moved near c-myc, might stimulate inappropriate transcription of this gene. To evaluate this hypothesis, we have tested the ability of the two known H chain enhancers, the JH-C mu intronic enhancer and the 3' alpha enhancer, to support transcription from c-myc promoters, by using transient transfection assays in a panel of 32 SNCL cell lines with 8;14 translocations. The activity of the JH-C mu intronic enhancer varied widely among the cell lines tested and correlated with the presence of nuclear factors binding to the E4/octamer regions of the enhancer. The 3' alpha enhancer was much less active than the intronic enhancer in all of our cell lines and seems unlikely to account for the c-myc deregulation (although the enhancer we tested was from the rat, because the human homologue is unidentified at present). A marked difference was also seen in the ability of individual cell lines to support transcription from the unenhanced c myc constructs. Cell lines supporting the lowest enhancer activity tended to support the highest level of transcription from unenhanced c-myc promoters. The differences in transcription from c-myc promoters were confirmed by stably transfecting constructs containing c-myc promoters in SNCL cell lines. Our data strongly suggest that the importance of Ig enhancers for c-myc deregulation varies markedly in different cell lines and that, for many, trans-acting regulators of the c-myc promoters are as important or more important, than Ig enhancers in the deregulation of the c-myc gene. PMID- 8515069 TI - Detection of T and B cells in many animal species using cross-reactive anti peptide antibodies. AB - A wide range of lineage-specific Ag are detectable in the human lymphoid system using mAb, but only a few such markers are detectable in animal species. In this paper, we have investigated the interspecies reactivity of antibodies raised against intracytoplasmic peptide sequences from two T cell Ag (CD3 and CD5) and two B cell markers (the Ig-associated polypeptides encoded by the mb-1 and B29 genes). Immunocytochemical labeling of tissue sections showed that these antibodies cross-react widely between different species (including ungulates, rodents, and marsupials), staining B or T cell areas selectively in lymphoid tissue. The specificity of these antibodies for the animal homologues of the human T and B cell markers was confirmed for the rat by Western blotting analysis. The broad cross-reactivity of these antibodies appears to be due to the fact that they were raised against intracytoplasmic peptide sequences that are highly conserved between humans and rodents, i.e., 80% for mb-1, 85% for CD5, and 100% for CD3 and B29. This strategy should, in the future, widen the range of lineage-associated markers detectable in experimental animals. PMID- 8515070 TI - Differential expression of 13 IgA-heavy chain genes in rabbit lymphoid tissues. AB - Molecular cloning techniques have recently demonstrated that rabbit has 13 different IgA C alpha H chain genes. This is in contrast to human and mouse that have only two and one C alpha heavy chain genes, respectively. In previous studies, nucleotide sequence analysis indicated that the 13 rabbit C alpha genes were potentially functional, and in vitro expression experiments showed that at least 12 of these genes were expressible. To understand the role of these multiple IgA isotypes we analyzed RNA of various lymphoid tissues for the presence of mRNA representing each of the multiple C alpha genes. We used the RNase protection assay with probes that are specific for the 13 different C alpha genes and we consistently found that at least 10 of the C alpha genes are expressed, albeit at different levels, in gut (small intestines), appendix, mesenteric lymph node, and mammary tissue. However, in salivary gland (submandibular), only seven of these genes are expressed at significant levels and in lung and tonsil only one C alpha gene, C alpha 4, is expressed at a level comparable to its expression in other tissues. Analysis of RNA of Peyer's patch showed differences in the level of C alpha gene expression between different animals and between different Peyer's patches of the same rabbit; in some cases, most of the C alpha genes were expressed, but in some cases only C alpha 4 was expressed at a significant level. Inasmuch as C alpha 4 is the 5' most C alpha gene we propose that IgA-producing cells are derived from B cells that have initially undergone isotype switching to C alpha 4 and we discuss various mechanisms that could explain switching to the more 3' C alpha genes. PMID- 8515071 TI - Differentiation of human lambda I variable regions with a monoclonal antibody to a defined, germ-line-encoded idiotope correlates with V lambda Ia chemical structure. AB - This article describes the characterization of a mouse monoclonal anti-idiotypic antibody (1H7B) prepared against a human monoclonal rheumatoid factor (RFSJ2) whose L chain utilized a V lambda I subgroup gene. The mAb 1H7B reacted with 6 of the tested 12 human V lambda I proteins, as well as with a newly produced lambda mAb whose V lambda gene usage has not as yet been determined. Because six of the 1H7B-positive mAb were heterogeneous with respect to both their VH gene utilization and antigenic specificity, and because mAb 1H7B did not react with any of the tested 43 kappa or 12 lambda proteins belonging to various subgroups other than V lambda I, mAb 1H7B appeared to be a V lambda I subgroup-specific reagent. The L chain specificity of mAb 1H7B was confirmed by Western blotting, and the inhibition of RFSJ2 binding to human Fc gamma by 1H7B provided additional evidence for the V region specificity of mAb 1H7B. The 11 sequenced V lambda I proteins used in this study were assigned to sub-subgroups by comparison with the previously published germ-line V lambda Ia, V lambda Ib, and V lambda Ic sequences. The mAb 1H7B only appeared to recognize V lambda Ia proteins as it reacted with five of the seven V lambda Ia, but not with three V lambda Ib or with one V lambda Ic protein. Because mAb 1H7B reacted with at least one V lambda Ia sequence in germ-line configuration, it appeared to be a marker for V lambda Ia sub-subgroup germ-line gene(s). The idiotope recognized by 1H7B was localized to the first framework region by inhibiting its binding to RFSJ2 with a synthetic peptide to the 11-24 amino acid region of V lambda Ia L chains. Comparison of the V lambda 1-24 region sequence of RFSJ2 with those of the two 1H7B-negative V lambda Ia mAb revealed a single amino acid difference at position 17, suggesting that the idiotope recognized by 1H7B encompassed this position. PMID- 8515072 TI - Leishmania antigens presented by GM-CSF-derived macrophages protect susceptible mice against challenge with Leishmania major. AB - Leishmania major, a causative agent of leishmaniasis, in humans is also capable of infecting mice. Several strains of mice, including the BALB/c strain, are unable to mount appropriate T cell responses to the parasite and develop a fatal, disseminated infection. We present evidence that injection of granulocyte macrophage-CSF derived bone marrow macrophages (GMM phi), previously incubated with L. major antigens, into BALB/c mice before infection, induced a Th1 dominated response and subsequent healing. Injection of BALB/c mice with GMM phi pulsed with irrelevant Ag, or other macrophages pulsed with L. major Ag, failed to protect against L. major challenge. Protection induced by L. major Ag-bearing GMM phi correlated with the induction of a Th1-like response with the production of high levels of IFN-gamma, delayed-type hypersensitivity reactivity and long lived resistance to reinfection. GMM phi-T cell interaction, rather than parasite killing by GMM phi, appeared to be a crucial step and there was a strong correlation between ability to function as APC in vitro and induction of protective immunity in vivo. These data suggest that presentation of Ag by a population of L. major Ag-bearing GMM phi can activate Th1 cells in BALB/c mice, leading to a protective immune response to parasite invasion. This implies that the nature of the APC population which presents Ag may influence the response to that Ag in vivo. PMID- 8515073 TI - Immunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy. AB - IL-10 and IL-4 have been shown to exert an inhibitory effect on cell-mediated immune responses. Our previous studies of leprosy demonstrated that IL-10 and IL 4 mRNA were preferentially expressed in lesions from lepromatous patients, those immunologically unresponsive individuals that manifest widespread infection. To define more precisely the regulatory roles of these two cytokines in the immune response to infection, we studied in vitro responses to Mycobacterium leprae. M. leprae triggered IL-10 release from PBMC of patients and healthy donors; the predominant source of the IL-10 was found to be monocytes/macrophages. Stimulation of PBMC in the presence of neutralizing anti-IL-10 mAb indicated that endogenous IL-10 production inhibits PBMC proliferation and release of TNF-alpha, GM-CSF, and IFN-gamma. Paradoxically, studies using neutralizing anti-IL-4 mAb indicated that endogenous IL-4 production enhances PBMC proliferative responses most strikingly in lepromatous patients. We found that rIL-4 expanded CD8+ T cells from lepromatous patients in vitro. CD8+ T cells from lepromatous patients have been shown to suppress CD4+ T cell responses, in part by the release of IL 4. Our study indicated that endogenous IL-4 production inhibited IL-10 secretion and, concomitantly, increased TNF-alpha and GM-CSF release. The present data suggest that, on balance, IL-4 and IL-10 contribute to immunosuppression in human infectious disease. PMID- 8515074 TI - IFN-gamma-mediated antimicrobial response. Indoleamine 2,3-dioxygenase-deficient mutant host cells no longer inhibit intracellular Chlamydia spp. or Toxoplasma growth. AB - The role of indoleamine 2,3-dioxygenase (IDO) in IFN-gamma-mediated inhibition of intracellular parasite growth has been examined previously, although earlier work has been largely correlative. In this study, we defined more completely the role of IDO in the IFN-antimicrobial response. Two mutant cell lines, derived from ME180 cells and exhibiting reduced IDO activity (IR3B6A, IR3B6B) were characterized to determine if they retained the capacity to inhibit intracellular Chlamydia and Toxoplasma growth. Mutant cells treated with IFN-gamma exhibited reduced capacity to suppress pathogen growth. The expression of several IFN regulated genes also was measured to confirm that the inability to inhibit pathogen growth was because of the lack of IDO. The expression of class II MHC, intracellular adhesion molecule-1, MxA, and P68 kinase genes was induced in the IFN-gamma-treated wild type ME180 cells, but was variable in the mutant cell lines, supporting the hypothesis that IFN-gamma-induced production of IDO is a key IFN-gamma-mediated antimicrobial mechanism. PMID- 8515075 TI - Transcriptional activation of the macrophage colony-stimulating factor gene by IL 2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B. AB - Human peripheral blood monocytes (Mo) constitutively display the beta-chain of the receptor for IL-2, whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2. Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF (M CSF) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody. Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF kappa B to its recognition sequence in the 5' regulatory enhancer region of the M CSF gene. Moreover, using a heterologous promoter (herpes thymidine kinase) construct containing the NF-kappa B consensus sequence, it is shown that NF-kappa B binding by an IL-2-induced monocyte-derived nuclear protein confers reporter gene (human growth hormone) activity. Taken together, our findings indicate that IL-2 induces gene expression of M-CSF in human blood-derived Mo and provide evidence for involvement of NF-kappa B in transcriptional regulation of this gene. PMID- 8515076 TI - Amyloid precursor protein in peripheral mononuclear cells is up-regulated with cell activation. AB - The deposition of beta/A4 protein in extraneural organs of patients with Alzheimer disease suggests that this peptide may in part be derived from a peripheral precursor. We studied expression of amyloid precursor protein (APP) in PBMC. APP expression was detectable in resting PBMC by northern blot analysis, immunoblotting studies, and immunohistochemistry. By reverse transcription polymerase chain reaction, the 751 and 770 APP transcripts containing the Kunitz protease inhibitor (KPI) domain were approximately 10-fold more abundant than the 695 transcript lacking the KPI domain. Activation of PBMC with the lectin PHA-P was associated with an increase in apparent intracellular APP content by cytofluorometry, and an increase in the proportion of the 695 APP transcript lacking the KPI domain. We conclude that resting and activated PBMC express APP and could contribute to a circulating pool of this protein. In addition, PBMC APP is up-regulated with mitogenic stimulation and may participate in the regulation of activation of these cells. PMID- 8515077 TI - Th2 cells mediate IL-4-dependent local tissue inflammation. AB - We investigated whether polyclonal murine Th1 and Th2 cells obtained after short term culture in vitro were capable of mediating tissue inflammation in vivo. Th cells were pulsed with mAb to the TCR/CD3 complex and injected into the footpads or ears of naive syngeneic recipient mice. Th1 induced delayed swelling that peaked at 24 to 48 h and lasted > or = 5 days. Th2-induced swelling peaked at 6 h and lasted < or = 48 h. Similar responses were also observed in athymic nude mice. Lesions with both Th1 and Th2 cells contained a predominant neutrophilic infiltrate at 6 h, and mainly mononuclear cells at 48 h. The inflammatory response with Th2 was blocked by cyclosporin A, by mAb to IL-4 or by soluble rIL 4R. The requirement for IL-4 was early and transient. Four alloreactive short term Th2 clones induced swelling in allogeneic recipients. mAb- and IL-4 dependent swelling responses were also observed with two long term Th2 clones. Our results demonstrate that Th2 cells mediate IL-4-dependent tissue inflammation, and strengthen the concept that Th2 cells play an important role in some T cell-dependent immune reactions and, possibly, in allergic disorders such as atopic dermatitis and allergic asthma. PMID- 8515078 TI - Selective regulation of metalloproteinase inhibitor (TIMP-1) by oncostatin M in fibroblasts in culture. AB - Tissue inhibitor of metalloproteinases (TIMP-1) is a potent inhibitor of activated matrix metalloproteinases (MMP) such as collagenase, stromelysin, and gelatinase, and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells. Since various cytokines and growth factors can modify the production of MMP and TIMP-1, we explored the action of oncostatin M (OM), a unique lymphocyte- and monocyte-derived cytokine, on expression of these proteins. We examined the regulation of TIMP-1 expression in cultured human fibroblasts by cytokines including OM, IL-6, leukemia inhibitory factor (LIF), and IL-1 alpha. When used at levels of 5 to 50 ng/ml, OM, IL-6, LIF, and IL-1 alpha elevated the TIMP-1 expression at the RNA level in fibroblasts of lung or synovial origin. Interestingly, OM stimulation resulted in highest levels of TIMP 1 RNA and protein synthesis. However, unlike IL-1 alpha, the cytokines OM, IL-6, and LIF did not induce MMP or PGE2 release. OM also enhanced TIMP-1 mRNA levels in the H2981 lung carcinoma and HepG2 hepatoma cell lines. The results suggest that OM as well as IL-6 and LIF, other cytokines acting through similar receptor pathways, may act to inhibit net MMP activity by specifically up-regulating TIMP 1 expression. The selective induction of TIMP-1 by OM may be influential in altering matrix destruction in chronic inflammation and tumor metastasis. PMID- 8515079 TI - Microbial superantigens induce NF-kappa B in the human monocytic cell line THP-1. AB - Staphylococcal superantigens bind to MHC class II molecules and induce transcriptional activation of IL-1 beta and TNF-alpha genes in human monocytic cells. The understanding of the mechanisms by which superantigens activate cytokine gene expression is incomplete. In this study, we demonstrate that toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins A and B induce the activation of NF-kappa B, a transcriptional enhancer that binds to sequences found in both the IL-1 beta and TNF-alpha promoters. Electrophoretic mobility shift assays showed a rapid induction of nuclear proteins that bound to the consensus kappa B motif. Furthermore, TSST-1 potently stimulated chloramphenicol acetyltransferase (CAT) expression by THP-1 cells transfected with a consensus NF kappa B-promoter CAT construct, indicative of induction of NF-kappa B enhancer function. Induction of both NF-kappa B DNA-binding proteins and NF-kappa B enhancer function was down-regulated by inhibitors of protein kinase C and protein tyrosine kinase, indicating a role for these protein kinases in the induction of NF-kappa B by MHC class II ligands. Using neutralizing antibodies, we demonstrated that after the stimulation of cells with TSST-1, TNF-alpha, but not IL-1 beta, acted to up-regulate binding of NF-kappa B to DNA and the activation of the NF-kappa B-promoter CAT construct. These results indicate that induction of NF-kappa B by superantigens is up-regulated in part by an autocrine loop involving TNF-alpha. PMID- 8515080 TI - IL-1 and transforming growth factor-beta inhibit platelet-derived growth factor AA binding to osteoblastic cells by reducing platelet-derived growth factor-alpha receptor expression. AB - Platelet-derived growth factor (PDGF) is thought to play a significant role in bone repair and regeneration. We previously demonstrated that PDGF-AA-induced chemotaxis and proliferation can be modulated by IL-1. We now report that IL-1 and transforming growth factor-beta (TGF-beta) significantly decrease the number of PDGF-AA binding sites in both normal and tumor-derived human osteoblastic cells, whereas PDGF-BB binding is minimally affected. The affinity of PDGF-AA binding remains unchanged in the presence of IL-1, but is slightly reduced by TGF beta as demonstrated by Scatchard analysis. We also showed that tyrosyl kinase phosphorylation after PDGF-AA binding is decreased in the presence of both IL-1 and TGF-beta. Northern blot analysis indicates that both IL-1 and TGF-beta decrease the expression of PDGF-alpha receptor mRNA. These results suggest that IL-1 and TGF-beta have the potential to regulate PDGF-AA-induced biologic activity in normal human osteoblastic cells and in human osteoblastic sarcoma cells by decreasing the levels of the PDGF-alpha receptor. PMID- 8515081 TI - Construction of an HIV-1 peptide vaccine containing a multideterminant helper peptide linked to a V3 loop peptide 18 inducing strong neutralizing antibody responses in mice of multiple MHC haplotypes after two immunizations. AB - Peptide constructs comprised of multideterminant Th peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52 to 73% of HIV positive, Ag-responsive patients, were colinearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB. The segments containing clusters of overlapping Th epitopes were called cluster peptides. Cognate help for peptide 18 antibody was elicited after a single immunization in all strains of mice that had previously responded to a T cell epitope encompassed by the cluster peptides. Animals boosted with cluster peptide-peptide 18 constructs 36 to 52 wk later displayed secondary antibody responses. Cluster peptide 3-peptide 18 induced antibody that neutralized homologous virus in one strain of mice although strong peptide 18 antibody responses were detected in all four strains of mice. The most promising construct, cluster peptide 6-peptide 18, induced neutralizing antibody in all strains of mice tested, and in two strains the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, antibody titers for 90% neutralization in the range of 1/1000 to 1/16,000 were achieved. These neutralizing titers against the homologous viral strain, after just two immunizations, are at least four- to eightfold higher than the highest titered other polyclonal V3-specific immune sera we have ever observed in our laboratories. We also asked why some sera neutralized and others with similar ELISA titers did not. No correlation was found between neutralization and isotype or affinity for peptide or gp 120. We could not account for neutralization by antibodies to the helper sites. Substitutions made in the central loop region of peptide 18, amino acid residues PGRAF, dramatically reduced binding of both neutralizing and non-neutralizing sera although some fine specificity differences between neutralizing and nonneutralizing sera were noted. These results have implications for the design of synthetic peptide vaccines for HIV. PMID- 8515082 TI - Expression of prolactin receptors in murine lymphoid cells in normal and autoimmune situations. AB - We have analyzed the expression of prolactin receptors (PRL-R) on murine lymphoid cells by using flow cytofluorometry analysis with biotinylated anti-PRL-R mAb raised against several epitopes of the extracellular domain of the PRL-R and by using polymerase chain reaction amplification. We demonstrated that PRL-R were universally expressed in normal rat and mouse hematopoietic tissues. In both primary lymphoid organs, namely, thymus and bone marrow, > 90% of cells were labeled by the anti-PRL-R mAb, but the density of PRL-R (assessed by fluorescence intensity) was lower on thymocytes than on bone marrow cells. In peripheral lymphoid organs there were smaller proportions of cells bearing PRL-R and we could clearly distinguish cell subsets of various fluorescence intensities. By using classical markers for lymphoid cell populations, we noted that all B cells and macrophages from spleen, lymph nodes, and blood strongly expressed the PRL-R. Regarding T cell populations, large proportions (> 85%) of PRL-R+ cells were detected in the four thymocyte subsets, thus contrasting with the smaller proportions (50 to 65%) of T cells labeled in the periphery. Similar percentages of PRL-R+ cells were observed in CD4+ and CD8+ peripheral lymphocyte subsets. Importantly, the stimulation of thymocytes and spleen cells with the T cell mitogen Con A promoted an enhancement of the density of PRL-R molecules on the cell membranes. Because hyperprolactinemia is associated with some autoimmune diseases, we also investigated PRL-R expression in the NZB autoimmune mouse. In contrast to the pattern observed in normal animals, the frequencies of PRL-R bearing T cells as well as the density of PRL-R per cell increased with age in NZB mice, suggesting that some imbalances of PRL/PRL-R interaction might occur in autoimmune situations. In conclusion, our data provide a molecular basis for a better understanding on the mode of action of PRL within the immune system in physiologic and pathologic situations. PMID- 8515083 TI - Characterization of T cells infiltrating the heart in rats with experimental autoimmune myocarditis. Their similarity to extrathymic T cells in mice and the site of proliferation. AB - A model of experimental autoimmune myocarditis, which resembles fatal giant cell myocarditis in humans, was previously established in rats immunized by s.c. injection of human cardiac myosin. We characterized herein the surface phenotype of lymphocytes infiltrating the heart and pericardial cavity as well as of mononuclear cells in various organs by using mAb in conjunction with immunofluorescence tests. Since profound thymic atrophy always accompanied the diseased states, attention was focused on characterization of T cells with properties similar to those of extrathymic T cells. In mice, extrathymic T cells were activated in association with thymic atrophy, expressed high levels of LFA-1 and IL-2R beta-chains, and contained a significant proportion of double negative CD4-CD8- T cells. In diseased rats, a large proportion of activated T cells that expressed high levels of LFA-1 and IL-2R was demonstrated in the pericardial effusion and heart tissue. Such T cells were rare in the other organs. Light scatter and microscopic observation revealed that activated lymphoblasts were most abundant in the pericardial effusion. Moreover, one-fourth of such T cells in the pericardial effusion displayed double negative phenotype. These cells in rats might correspond to the extrathymic T cells in mice. However, only a limited population of such activated T cells infiltrated the heart tissue. Concerning the location of such T cells mainly in the outer layer of the heart, it raised the possibility that extrathymic T cell differentiation in these autoimmune rats might occur in the pericardial cavity, and the differentiated cells then migrated to the sites of the cardiac lesion. PMID- 8515084 TI - Religation of the T cell receptor after primary activation of mature T cells inhibits proliferation and induces apoptotic cell death. AB - The proliferative response of murine splenic T cells, initially activated by cross-linking the TCR complex with either antibodies, mitogenic lectin, or alloantigen was severely inhibited when the activated cells were recovered and given an additional activation signal by recross-linking the TCR complex, or by adding Ca2+ ionophore and phorbol ester. Under the same conditions, cross-linking other T cell surface determinants such as CD4, CD8, or class I MHC on preactivated T cells had no effect. Assessment of cell viability using vital dye exclusion together with the detection of DNA fragmentation revealed that the reduction of the proliferative responses was associated with an induction of apoptotic-like cell death in the activated T cell population and not due to a blockade of cell division. Accumulation of eosin stained (dead) cells did not occur immediately upon replating the activated cells, but began after a lag period during which at least two cell divisions occurred. In addition, perturbation of T cell proliferation after activation depended on how the cells were initially activated. Only T cells activated in the presence of additional cells found in spleen and lymph node were susceptible to inhibition; T cells activated after nylon wool purification were not susceptible. These results have potential implications for understanding self-tolerance and immunoregulation. PMID- 8515085 TI - [Antenatal screening of uropathies. A 4-year experience, 147 patients]. AB - We have received 147 patients with an antenatal diagnosis of uropathy confirmed after birth. Surgery during the first 3 months of life was necessary for 78 (54%) of them. The procedures included partial or total exeresis of the kidney in 9 cases, and reconstruction of the excretory pathway in 69 (88%). The renal function is normal in all cases, and one failure of surgery only was noted. Four children with pelviureteral obstruction had infections in spite of the antenatal screening, as did one child with reflux. One child remained with a postoperative urinary infection, which can be attributed to contralateral reflux. In surgery of the renal pelvis, as well as in the reimplantation of thin ureters, no tube was left in place, thus reducing the stay in hospital and the risk of post-operative infection. The children were admitted to hospital with their mothers in 95% of all cases. PMID- 8515086 TI - [Retrospective comparative study of three surgical procedures in the treatment of urinary stress incontinence in women. Apropos of 119 patients treated from 1985 to 1990]. AB - From 1985 to 1990, 119 female patients underwent a cure for urinary incontinence on exertion according to a technique that varied according to the period and to the data of the literature. From 1985 to 1988, 42 patients were operated with the Goebbel-Stoeckel technique; from 1986 to 1988, 32 patients were operated with Stamey's procedure, and 47 patients with Gittes' procedure from 1988 to 1990. These three groups of patients with comparable ages, previous history and degree of urinary incontinence on exertion were analyzed by the same surgeon for functional results and morbidity, both in the immediate three months after surgery and in July, 1991, with an average distance in time of 29 months. The patients with no leakage of urine were regarded as healed, those presenting with occasional leakages on violent exertion but requiring no napkins were regarded as improved. All other patients were regarded as failures. The percentage of failure is similar for the three technical procedures when analyzing long-term results and according to our criteria, 66% of patients only are healed or improved. These figures are noticeably higher if surgery has been performed in a patient with normal preoperative closing pressure. The analysis of this series and comparison with series in the literature seem to allow outlining a therapeutic pattern for urinary incontinence on exertion, whether recurrent or not, with or without sphincter hypotonia. PMID- 8515087 TI - [Ruptures of the bladder. Clinics, treatment, controversies]. AB - Since the bladder is well protected by the bony pelvis, it is seldom injured. However, the initial trauma may be a major one, and associated lesions are frequent, especially in case of extraperitoneal ruptures. Retrograde cystography still remains an essential examination, for which the technique must be straightforward. This work is a review of our cases of pure bladder rupture from 1981 to 1992. Investigations, treatment, and our results are discussed, and the literature is reviewed. In the last few years, we have been favoring a conservative approach of extraperitoneal lesions. PMID- 8515088 TI - [Urodynamic study of the behavior of detubulated ileocystoplasties according to feeding]. AB - Twenty-three patients having undergone enterocystoplasty with a detubulated graft has an urodynamic study on an empty stomach and after a standardized meal. All patients (average age 62.9 years) had been operated more than 6 months earlier, and 30% still presented with urine leakages at night. The urodynamic study included a cystomanometric measurement with rapid water filling, an urethral profile and a micturating cystography. It was repeated 60 to 90 minutes after a meal composed of glucids, lipids and protids. Feeding had variable effects on the intestinal graft: increase in peristaltic intensity and/or earlier onset of contractions (10/23); apparently paradoxical decrease in contractions (6/23); sometimes no modification (7/23). This short work without any obvious physiopathological explanation has led us to advocating breaking up feeding for patients who were improved by the meals. PMID- 8515089 TI - [The quality of conceptus as a function of father's age]. AB - Testicular ageing affects at the same time the individual and his lineage. In the individual, vascular, endocrine, blood testis barrier and Sertoli cells changes because of age lead a decrease of spermatozoa number and an alteration in their form and motility. These changes lead a gradual decrease of fertility. In the progeny, paternal ageing is responsible for new dominant autosomic mutations which themselves cause different malformations and perhaps for certain chromosome X linked recessive mutations. Moreover, in animal and man, paternal ageing seems responsible for a gradual lowering in the level of progeny cerebral functions. In man, very youthful age was also related to these effects. Maternal age did not appear to play a part in this event. On the whole, these results pose the problem of the optimum age for fatherhood. PMID- 8515090 TI - [Electrostimulation of anterior sacral nerve roots in the treatment of central neurogenic bladders. G.S. Brindley's technique. Results of the 40 first French cases]. AB - The results of the first 40 cases who underwent implantation of a sacral anterior root stimulator (G.S. Brindley) in France are reported. One patient die two years after implantation from an unrelated cause. 39 patients are using electrostimulation with a 6 month to 8 year follow-up. 90% have a satisfactory continence and no longer require an incontinence appliance. 82% of the patients have a post-void residue of 0 to 50 cc. Urinary infection rate has dramatically decreased. Bladder capacity and compliance have increased, and urethral closure pressure has decreased according to posterior rhizotomy. Possible side effect of total posterior rhizotomy from S2 to S4 could be stress incontinence. PMID- 8515091 TI - [Renal lymphoma in a transplanted patient treated with cyclosporine]. AB - The effectiveness of renal transplantation has been considerably improved by the use of cyclosporine as an antirejection agent. However, because of those very same immunosuppressive properties, this substance may lead to several infectious or tumoral complications that raise complex therapeutic problems. This article reports about one case of immunoblastic lymphoma discovered in a patient who received renal transplantation and who had been treated with cyclosporine for two years. PMID- 8515092 TI - [Urinary malacoplakia. Anatomoclinical analysis of 3 cases with long-term follow up. Review of the literature]. AB - Malakoplakia is a granulomatous disease. We report 3 cases of this condition. This disease is characterized by its rarity, the nonspecific revealing signs, histological studies being the only method providing a positive diagnosis, and the possibility of healing with a simple medical treatment. PMID- 8515093 TI - [Paratesticular rhabdomyosarcoma. Diagnostic and therapeutic indications]. AB - We report about a case of paratesticular rhabdomyosarcoma diagnosed and treated in our Urology department. We bring a brief discussion about the diagnostic and therapeutic attitudes, and also a review of the literature. PMID- 8515094 TI - [Association of angiomyolipoma and oncocytoma of the kidney. Apropos of two cases]. AB - The association of an oncocytoma and of an angiomyolipoma within the same renal tumor is infrequent. The authors review the literature on the basis of two cases. Histogenesis and the clinicopathological analysis show that such an association is accidental. It makes up 0.5% of kidney tumors, and 1% of oncocytomas are associated with an angiomyolipoma. The risk to encounter a malignant tumor is of 25% in such cases. PMID- 8515095 TI - [Urinary diversion by ureteral endoprosthesis during pregnancy]. AB - Dilatation of the renoureteral cavities during pregnancy is a common occurrence, especially on the right side. Though generally asymptomatic, this dilatation can be unfrequently complicated by pain and/or urinary infections that may cause severe infectious and obstetrical complications. In such cases, drainage of the renal cavities may be indicated in very selected cases. The authors review their experience with renal bypass through an endoureteral prosthesis during pregnancy, and specify the technical aspects and the indications of this type of bypass. PMID- 8515096 TI - Parvovirus B19 infection in human immunodeficiency virus type 1-infected persons failing or intolerant to zidovudine therapy. AB - To determine the incidence of B19 infection in patients with AIDS who were being treated with dideoxyinosine, serial sera (n = 28) taken over a 2-year period from 14 individuals were analyzed with respect to anti-B19 serology and the presence of B19 DNA. All 14 individuals were anti-B19 IgM negative. Nine of 14 had B19 viremia by Southern analysis of polymerase chain reaction product. Five of 9 with B19 viremia had > or = 1 anti-B19 IgG-positive sample; none of 5 without viremia had anti-B19 IgG. Four of 9 viremic individuals had serially positive samples. All 4 had severe anemia (hemoglobin < 8.5 g/dL) while taking zidovudine. A fifth individual whose severe anemia resolved after zidovudine was discontinued did not have B19 viremia. Therefore, a significant proportion of this group of patients with AIDS who developed severe anemia while receiving zidovudine had persistent B19 infection. These results suggest that B19 infection should be considered in anemic patients with AIDS. PMID- 8515097 TI - Mycobacterium tuberculosis in household contacts of human immunodeficiency virus type 1-seropositive patients with active pulmonary tuberculosis in Kinshasa, Zaire. AB - Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV 1)-seropositive index patients and in 692 household contacts of 95 HIV-1 seronegative [corrected] index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis. PMID- 8515098 TI - Randomized, placebo-controlled trial of rifampin, ethambutol, and ciprofloxacin for AIDS patients with disseminated Mycobacterium avium complex infection. AB - Patients with AIDS and disseminated Mycobacterium avium complex (MAC) infection received rifampin (600 mg) plus ethambutol (25 mg/kg) plus ciprofloxacin (750 mg) or matching placebos daily for 8 weeks. Patients were monitored every 2 weeks clinically and by quantitating MAC colony-forming units (cfu) per milliliter of blood. Analysis of baseline characteristics revealed no significant differences between groups. After 8 weeks, MAC cfu had decreased by > or = 1 log/mL in 4 of 9 treated patients versus 0 of 10 placebo recipients while increasing by > or = 1 log/mL in 1 and 7, respectively (P = .006). While the average combined clinical response score declined in both groups, it tended to decrease less in treated patients (P = .36). On the other hand, dose-limiting toxicity (primarily nausea and adverse drug interactions) occurred in 9 of 12 treatment versus 1 of 12 placebo patients (P = .005). Combined rifampin [corrected]-ethambutol ciprofloxacin therapy for disseminated MAC infection had significant microbiologic efficacy with some evidence of clinical efficacy but was associated with drug intolerance. PMID- 8515099 TI - Recombinant interferon-gamma preserves human granulocyte bactericidal and chemoluminescence activities. AB - The effects of recombinant human interferon (IFN)-gamma on functions of human granulocytes (PMNL) were investigated. Incubation with IFN-gamma for up to 24 h enhanced the chemoluminescent (CL) response of polymorphonuclear leukocytes (PMNL) to Staphylococcus aureus, FMLP, opsonized zymosan, and PMA in a dose dependent fashion for concentrations of 1-1000 units/mL. Short exposures to tumor necrosis factor (TNF)-alpha also enhanced the CL responses of PMNL, but the effects IFN-gamma and TNF alpha together, at the concentrations used, were less than additive. Incubation of PMNL for 8 h with IFN-gamma preserved their bactericidal capabilities relative to control PMNL incubated for the same length of time without IFN-gamma. Preservation of neutrophil function may be a subtle but important role for IFN-gamma. PMID- 8515100 TI - Lipopolysaccharide and peptidoglycan share binding sites on human peripheral blood monocytes. AB - p73, a binding site for lipopolysaccharide (LPS) on human peripheral blood monocytes was identified using the radiolabeled photoaffinity cross-linker sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). The 125I-labeled conjugate of SASD and LPS (125I-labeled ASD-LPS) was bound to monocytes and UV cross-linked, and the cellular extracts were analyzed with two dimensional SDS-PAGE and autoradiography. In addition to the major binding site on human monocytes at 73 kDa, isoelectric point 5.95, there were multiple minor binding sites that recognized both smooth and rough LPS. Binding of 125I-labeled ASD-LPS to monocytes is concentration dependent, decreased in the absence of calcium and magnesium, and inhibited by either excess LPS or the low-molecular weight soluble isolate of bacterial cell wall peptidoglycan (sPGN). However, sPGN only minimally stimulates tumor necrosis factor (TNF) secretion by human peripheral blood mononuclear cells. In contrast, the relatively insoluble high molecular-weight peptidoglycan significantly stimulates TNF secretion. PMID- 8515101 TI - Experimental infection of the mouse brain by a relapsing fever Borrelia species: a molecular analysis. AB - The spirochetal disease relapsing fever is notable not only for multiphasic antigenic variation but also for central neurologic manifestations. To further characterize involvement of the brain in this disorder, immunocompetent and deficient mice were infected with Borrelia hermsii. Immunodeficient mice were treated while spirochetemic with neutralizing IgM monoclonal antibodies to the infecting serotype. Blood, cerebrospinal fluid, and brain tissue were examined by culture and polymerase chain reaction. In immunocompetent mice, antigenic variation occurred in the brain as well as in the blood. In immunodeficient mice, the infecting serotype was still present in the brain after it had been eliminated from the blood by the administered antibodies. These latter results cannot be accounted for by contamination of brain tissue and cerebrospinal fluid by blood and, hence, establish the direct involvement of the central nervous system in this experimental infection. PMID- 8515102 TI - Acellular pertussis vaccines--a solution to the pertussis problem? AB - The expanded knowledge of the components of Bordetella pertussis has led to the production of new vaccines consisting of one or more components of the organism. The vaccines have been found to be safe and immunogenic in infants and children. Early efficacy studies failed to determine what component of the vaccine and what level of antibody were needed for protection; additional studies with many more vaccines are currently in progress. The role of adults as reservoirs of B. pertussis infections and as victims of symptomatic disease has also been appreciated. Component vaccines have been found to be safe and immunogenic in adults. There is reason to hope that within the next several years the information derived from ongoing and planned studies will support the general use of component acellular pertussis vaccines for the routine immunization of adults and children alike. PMID- 8515103 TI - Comparative prophylactic efficacy of cefazolin and vancomycin in a guinea pig model of Staphylococcus aureus wound infection. AB - The increasing prevalence of methicillin-resistant Staphylococcus aureus as a wound pathogen in some institutions has prompted the use of vancomycin for surgical prophylaxis, although clinical data comparing vancomycin and cephalosporins are not available. A guinea pig model was used to compare the efficacy of vancomycin and cefazolin in preventing intermuscular abscess formation by 7 S. aureus strains. Both antibiotics were administered to achieve peak serum levels at the time of bacterial inoculation, and each remained > 1 micrograms/mL for a comparable duration. Vancomycin provided equivalent protection from infection by 1 methicillin-susceptible strain and significantly better protection against 4 methicillin-susceptible and both methicillin resistant S. aureus strains. For most strains, the bacterial inoculum with a 50% probability of causing an abscess was 2 to 4 log10-fold higher with vancomycin than cefazolin prophylaxis. Prophylaxis with vancomycin is superior to cefazolin in preventing intermuscular infection by methicillin-susceptible and -resistant S. aureus. PMID- 8515104 TI - Evidence for the introduction of a multiresistant clone of serotype 6B Streptococcus pneumoniae from Spain to Iceland in the late 1980s. AB - Almost all of the multiresistant pneumococci that appeared suddenly in clinical specimens in Iceland between 1989 and 1992 belonged to serogroup 6. Fifty-seven of these isolates were analyzed for serotype, penicillin-binding protein pattern, multilocus enzyme genotype, and fragmentation pattern obtained by pulsed-field electrophoretic separation of restriction enzyme digests of chromosomal DNA. All isolates were of serotype 6B and had similar or identical patterns in each molecular test. The Icelandic isolates were indistinguishable from a subgroup of multiresistant serotype 6B pneumococci that has been present with high incidence in Spain during the past two decades. The data suggest the import to Iceland of a single multiresistant clone of pneumococcus, most likely from Spain. PMID- 8515105 TI - Liposomes with prolonged blood circulation and selective localization in Klebsiella pneumoniae-infected lung tissue. AB - Studies of two types of small liposomes, differing with respect to their lipid composition in terms of bilayer fluidity, charge, and hydrophilicity of the liposomal surface, were done to evaluate their usefulness for delivery of encapsulated therapeutic agents to sites of infection. The liposomes showed substantial localization in infected lung tissue after intravenous administration. This was demonstrated in a model of unilateral Klebsiella pneumoniae pneumonia in rats, in which the left lung was infected but the right lung of the same animal developed no infection. The degree of localization in the infected left lung was different for the two types of liposomes. For the liposome type with the longer blood residence time, containing a surface coating of polyethylene glycol, localization in the infected left lung was dependent on the liposomal dose, correlated with the intensity of infection, and reached 9% of the injected liposomal dose in severely infected rats. PMID- 8515106 TI - An ancestral mutation enhancing the fitness and increasing the virulence of Haemophilus influenzae type b. AB - Capsulate Haemophilus influenzae is a major cause of septicemia and meningitis in children. Virtually all invasive strains have a type b polysaccharide capsule and belong to division I of the two phylogenetic divisions into which the H. influenzae population segregates. In this study 18 isolates, collected from all over the world and representative of the whole population of division I type b strains, have been shown to be the progeny of a common ancestor in which a founder mutation occurred, the deletion of one of two copies of the gene bexA. BexA is essential for exporting capsular polysaccharide to the bacterial surface, and a single copy of its gene lies at the center of an otherwise duplicated capsulation locus. Deletion of the other copy has had the paradoxical effect of enhancing pathogenicity, through increasing the potential for amplification of capsule biosynthetic genes and capsule production. PMID- 8515107 TI - Further evidence of host species-specific variation in antigens of Pneumocystis carinii using the polymerase chain reaction. AB - To further elucidate the extent of variation among Pneumocystis carinii obtained from different mammalian hosts, polymerase chain reaction (PCR) analysis of the genes encoding two antigens of P. carinii was done. Using primers based on the ferret P. carinii glycoprotein (gp)A gene and the rat P. carinii 45- to 55-kDa antigen gene, amplification was attempted with DNA isolated from P. carinii infected ferret, rat, mouse, and human lungs. For both genes, amplification was successful only with P. carinii DNA isolated from the same host species from which the P. carinii gene was originally isolated. The presence of P. carinii DNA in each sample was documented by PCR using primers based on the conserved mitochondrial ribosomal RNA gene sequence. These results were confirmed for P. carinii gpA by Southern blot analysis using a labeled fragment of the ferret P. carinii gpA gene as a probe. Thus, in addition to the previously reported phenotypic variation among antigens of P. carinii, there is also genotypic variation of these same antigens. PMID- 8515108 TI - Nosocomial acquisition of Candida albicans: an epidemiologic study. AB - To evaluate the mechanism and risk factors associated with the nosocomial acquisition of Candida albicans, a 10-month prospective study was conducted in a 24-bed bone marrow transplant unit and an 8-bed medical intensive care unit of a university hospital. A total of 98 patients had samples taken on admission and during hospitalization for culture. Samples from hands of hospital personnel and environmental surfaces were also cultured. C. albicans was isolated from 52 patients, and each patient was matched with a control. Fourteen patients acquired C. albicans after admission to the study. Prior antibiotics and length of time spent in the unit were more common in patients with new acquisition of C. albicans than in controls (92% vs. 64% and 32.5 vs. 13.0 days, respectively). Restriction enzyme analysis revealed 32 strain types; 4 were common to 30 patients and 10 environmental surfaces. Identical strains of C. albicans from patients who were geographically and temporally associated suggests the exogenous nosocomial acquisition of C. albicans through indirect patient contact. PMID- 8515109 TI - Albendazole in human loiasis: results of a double-blind, placebo-controlled trial. AB - To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia. PMID- 8515110 TI - Mother-to-child transmission of human immunodeficiency virus type 1: correlation with neutralizing antibodies against primary isolates. AB - The aim of this study was to investigate the influence of neutralizing antibodies in mother's serum on the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Sera from 20 HIV-1 infected mothers were analyzed for their ability to neutralize their own virus (autologous neutralization) and virus obtained from other mothers (heterologous neutralization). A statistically significant correlation was found between the capacity to neutralize 1 selected primary isolate and protection of the child from infection. Also, neutralizing antibodies against autologous virus were more frequently present in nontransmitting mothers than in transmitting mothers (5 and 2, respectively, of 10 mothers). The mothers with autologous neutralizing antibodies also neutralized at least 2 heterologous primary isolates. Thus, mothers with neutralizing antibodies to primary HIV-1 isolates have a reduced risk of infecting their children. PMID- 8515111 TI - Acellular pertussis vaccines--a solution to the pertussis problem. AB - Available data relating to pertussis and pertussis immunization are frequently overlooked or misinterpreted. Mortality due to pertussis is underreported. Most whole cell pertussis vaccines are effective; there is no evidence that pertussis vaccines cause brain damage. Moreover, acellular pertussis vaccines have been used successfully in Japan since 1981. Third-generation, genetically derived acellular pertussis vaccines have been developed, but knowledge of antigens and concentrations required has not kept pace with vaccine technology. There is substantial evidence that pertussis is not a single lymphocytosis-promoting factor (LPF) toxin disease. Pertussis vaccine efficacy studies suggest that monocomponent LPF toxoid or biocomponent LPF toxoid/filamentous hemagglutinin (FHA) vaccines are not as effective as vaccines that contain pertactin and fimbrial antigens as well as LPF toxoid and FHA. Future programs with multicomponent acellular vaccines and universal childhood immunization followed by booster doses in adults will effectively curtail disease incidence and the circulation of Bordetella pertussis. PMID- 8515112 TI - Early colonic damage and invasion of Campylobacter jejuni in experimentally challenged infant Macaca mulatta. AB - Experimental challenge studies with Campylobacter jejuni were conducted in 3.5 month-old infant Macaca mulatta. One infant monkey (92-1) was challenged with 2.7 x 10(10) cfu of strain 78-37. A second infant was infected intentionally by natural transmission. The infants developed diarrhea 32 h after challenge of infant 92-1. Electron microscopic observations indicate that cell invasion is the primary mechanism of colon damage and diarrheal disease caused by C. jejuni. Intracellular C. jejuni were located in membrane-bound vacuoles and were free in the cytoplasm. Damaged epithelial cells exhibited premature apoptosis and were exfoliated into the lumen of the colon. C. jejuni were also located extracellularly in the mucosa and submucosa. Some cells had dilated endoplasmic reticulum, indicating possible alteration in ion and water transport. PMID- 8515113 TI - Diarrhea associated with Aeromonas species in children in day care centers. AB - Outbreaks of diarrhea caused by enteropathogens have been reported in day care centers (DCC), but Aeromonas species have not been implicated. This study evaluated 381 children involved in 51 outbreaks in four DCC to determine the association of Aeromonas species with diarrhea and to characterize the isolates. The organism was identified in two outbreaks of diarrhea. In one, Aeromonas species were isolated from 6 (24%) of 25 children and in the other from 5 (21%) of 24 children. Seven other Aeromonas strains from children in DCC were studied. Fourteen (78%) of 18 were Aeromonas caviae and 15 were from children with diarrhea. Of the isolates, 75% did not have plasmids detected; all others had unique plasmid patterns. All strains had different DNA content. Twenty-two control isolates of Aeromonas from children with diarrhea in Mexico and Dallas had different chromosomal DNA patterns. Most Aeromonas infections were associated with symptoms. Chromosomal DNA patterns differentiated Aeromonas strains better than did plasmid DNA patterns. The outbreaks of diarrhea were unusual in that several different Aeromonas genospecies were involved in each outbreak. PMID- 8515114 TI - The cohort effect and Helicobacter pylori. AB - A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalence has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%-41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that H. pylori infection is becoming less frequent and is predominantly acquired in childhood. PMID- 8515115 TI - Seroprevalence of Helicobacter pylori in Chile: vegetables may serve as one route of transmission. AB - Helicobacter pylori infection is very common in Chilean adults, but the age related prevalence, risk factors for infection, and mode of transmission in Chilean children are unknown. An ELISA was used to test for H. pylori antibodies in 1815 Chileans < 35 years of age. Seropositivity was > 60% in lower socioeconomic groups. H. pylori seropositivity correlated with increased age, low socioeconomic status, and consumption of uncooked vegetables by use of a logistic regression analysis. Risk factors that reached marginal significance were consumption of uncooked shell-fish, female sex, and residence in Santiago. Although multiple modes of transmission for H. pylori undoubtedly exist, prior studies have suggested that contamination of irrigation water by raw sewage (and the subsequent contamination of vegetables that are eaten uncooked) is a key factor in the transmission of enteric pathogens in Chile; H. pylori may be transmitted by a similar route. PMID- 8515116 TI - Vaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component-deficient individuals. AB - This study sought to quantitate the response of late complement component deficient (LCCD) individuals to the meningococcal vaccine, to examine antibody persistence, and to investigate the contribution of these antibodies to meningococcal killing in complement- and phagocyte-dependent bactericidal assays. The mean concentration of antibody to group A and C capsular polysaccharide after vaccination was similar in 8 LCCD, 11 family members, and 7 unrelated normal individuals. LCCD individuals had a greater percentage decline in antibody concentration to group C polysaccharide and had lower concentrations of antibody to group Y polysaccharide 2.0-2.5 years after vaccination than did normal and heterozygous deficient persons. Antibody to subcapsular antigens was minimally effective in mediating complement-dependent killing and had no effect in the opsonophagocytic assay. In contrast, antibody to capsular polysaccharide promoted meningococcal killing in both assays. These data support vaccination as a preventive measure in LCCD individuals and lend credence to the idea that these individuals are critically dependent on capsular antibody for protection against meningococcal disease. PMID- 8515117 TI - Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis. AB - The role of tumor necrosis factor-alpha (TNF alpha) in the pathogenesis of severe bacterial infections has been studied extensively. However, the role of TNF beta, a lymphokine with biologic activities similar to those of TNF alpha, has received little attention. Therefore, the purpose of this study was to examine the production of TNF beta by peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) and the superantigens staphylococcal toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA). Though LPS was a more potent inducer of TNF alpha than was TSST-1 or SPEA, TSST-1 and SPEA were both more potent inducers of TNF beta. The superantigens TSST-1 and SPEA were more potent inducers of total TNF (TNF alpha and TNF beta) than was LPS. These data suggest that the induction of TNF beta synthesis may be a unique pathway by which superantigens associated with severe streptococcal and staphylococcal infections mediate shock and multiorgan failure characteristic of toxic shock syndrome. PMID- 8515118 TI - In vitro activity of sodium bisulfite and heparin against staphylococci: new strategies in the treatment of catheter-related infection. AB - Device-related infections often persist until the device is removed because systemic antibiotic therapy fails frequently. In an in vitro model, the activity of sodium bisulfite (an antioxidant added to many drugs) heparin with chlorbutol or chlorcresol as preservatives, and their combination with cefpirom for treating the internal surface of polyurethane and silicone catheters colonized with Staphylococcus aureus and Staphylococcus epidermidis was studied. Sodium bisulfite (0.05%) markedly reduced catheter colonization. Heparin combined with chlorbutol, 1000 micrograms/mL of cefpirom, and 0.05% of sodium bisulfite was not more effective than sodium bisulfite alone. A lesser effect was shown by treating adherent bacteria on both catheters with heparin plus preservatives alone. Not only antibiotics but also other substances with antibacterial activity should be evaluated for treatment and prophylaxis of catheter-related infection. PMID- 8515119 TI - Diagnosis of congenital syphilis by combining Treponema pallidum-specific IgM detection with immunofluorescent antigen detection for T. pallidum. AB - Most infants at risk for congenital syphilis can be identified easily by a positive maternal serologic test for syphilis. However, a diagnosis of congenital syphilis can be difficult to make in an individual infant. Seven infants with delayed-onset congenital syphilis and 101 newborns at risk for congenital syphilis were evaluated for characteristic physical findings and laboratory detectable abnormalities of congenital syphilis. By using a combination of Western blot for T. pallidum-specific IgM detection and immunofluorescent antigen detection for the identification of T. pallidum, a diagnosis of congenital syphilis was made in all 7 infants with delayed-onset congenital syphilis and 24 of the 101 newborns at risk for congenital syphilis. However, T. pallidum specific IgM was negative in 6 of the 24 newborns with congenital syphilis. T. pallidum-specific IgM detection alone is inadequate for the diagnosis of congenital syphilis. PMID- 8515120 TI - Blastocystis hominis: prevalence in asymptomatic versus symptomatic hosts. AB - Blastocystis hominis, other protozoans, and fecal leukocytes were tabulated on trichrome-stained fecal smears from 182 asymptomatic and 125 symptomatic control patients. No statistically significant difference in prevalence of B. hominis was found between the asymptomatic study group and the symptomatic control group; the clinical profile of subjects with B. hominis and those not infected was similar, and no correlation was found between the presence of B. hominis and that of fecal leukocytes. High concentrations of B. hominis were more frequent and more nonpathogenic protozoa were found in symptomatic patients than in those who were asymptomatic. PMID- 8515121 TI - Herpes zoster and human immunodeficiency virus infection: a cohort study of 101 coinfected patients. Groupe d'Epidemiologie clinique du SIDA en aquitaine. PMID- 8515122 TI - Soluble CD4 levels in human immunodeficiency virus-infected patients. PMID- 8515123 TI - Bacteremia, endotoxemia, and mortality in gram-negative sepsis: a reappraisal. PMID- 8515124 TI - Poliovirus vaccination: a trilogy. AB - The incidence of poliomyelitis has declined dramatically since the introduction and widespread use of inactivated (IPV) and live oral (OPV) poliovirus vaccines. In the United States, fewer than 10 cases of paralytic poliomyelitis are reported each year, and all cases are vaccine associated. In contrast, paralytic disease due to wild virus continues to be a problem in less developed nations, in part due to poor seroconversion rates after receipt of OPV. The recent introduction of enhanced potency IPV has stimulated the prospects for a combined vaccine schedule that will reduce the frequency of vaccine-associated paralytic polio and retain good mucosal protection. Recent studies suggest that two doses of enhanced potency IPV followed by two doses of OPV provide excellent systemic and local immunity against polioviruses 1, 2, and 3. PMID- 8515125 TI - Pharmacokinetics of liposomal nystatin in patients with human immunodeficiency virus infection. PMID- 8515126 TI - Distribution of Haemophilus influenzae type b outer membrane protein subtypes in different ethnic groups in Australia. PMID- 8515127 TI - Purified monoclonal antibody to endotoxin core fails to protect mice from experimental gram-negative sepsis. PMID- 8515128 TI - Failure to identify Borrelia burgdorferi in southern California ticks by DNA amplification. PMID- 8515129 TI - Clarification of dietary risk factors and religion in a botulism outbreak. PMID- 8515130 TI - Therapy with atovaquone for Cryptosporidium parvum infection in neonatal severe combined immunodeficiency mice. PMID- 8515131 TI - Vaccination in the 21st century. AB - Vaccination has been one of the great successes of 20th century medicine. The next century promises to continue that "golden age" through the use of new strategies made possible by the genetic manipulation of microorganisms. In particular, vectors that carry genes coding for important antigens, recombinants that produce proteins, reassortants containing mixtures of genes, and agents deleted for particular genes will be used for the purpose of vaccination. The author discusses the specific needs for new vaccines and speculates on the routine schedule of immunization in the next century. PMID- 8515132 TI - Infection of monocytes during measles. AB - Immune suppression has long been recognized to be a consequence of measles and a likely contributor to the secondary complications of this infection. Since measles virus can be isolated from peripheral blood leukocytes during the early phases of infection, it has been widely assumed that measles virus suppresses the immune system by replicating in and damaging T lymphocytes. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay able to detect wild-type strains of measles virus was applied to the study of peripheral blood mononuclear cells (PBMC) during natural measles virus infection. Measles virus RNA was detected by RT-PCR in monocyte-enriched adherent cells up to 6 days after the appearance of the rash. No viral RNA was detected in the lymphocyte-enriched nonadherent cell fraction. The numbers of virus-infected PBMC detected by in situ hybridization ranged from 1 in 125 to 1 in 2500. Dual staining identified infected cells as monocytes. It is concluded that the primary leukocytes infected during measles are monocytes, not lymphocytes. This cellular tropism has implications for understanding the immune suppression associated with measles. PMID- 8515133 TI - Gender differences in reported AIDS-indicative diagnoses. AB - To compare AIDS-defining conditions in women and men, US adult AIDS cases diagnosed between January 1988 and June 1991 and reported to the Centers for Disease Control and Prevention through June 1992 were examined. For most AIDS defining conditions, the prevalence was similar for women and men when differences in race/ethnicity and mode of transmission were accounted for. Pneumocystis carinii pneumonia was the most prevalent condition (> 50%) regardless of gender, race/ethnicity, or mode of transmission. By logistic regression analysis, among injection drug users, conditions reported significantly more frequently in women than in men include esophageal candidiasis (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.40-1.62), herpes simplex virus (HSV) disease (OR, 1.68; CI, 1.46-1.94), and cytomegalovirus (CMV) disease (OR, 1.43; CI, 1.18-1.73). More knowledge of the interrelationships in women between HIV infection and secondary opportunistic infections, including candidiasis and sexually transmitted disease (e.g., HSV and CMV) is needed. PMID- 8515135 TI - Increased phagocytosis and generation of reactive oxygen products by neutrophils and monocytes of men with stage 1 human immunodeficiency virus infection. AB - Flow cytometry was used to study phagocytic function and release of reactive oxygen products following phagocytosis by neutrophils (PMNL) and monocytes of heparinized whole blood from stage 1 human immunodeficiency virus type 1 (HIV-1) infected men. Phagocytic capacity was assessed by measuring uptake of Texas red labeled bacteria. Reactive oxygen generation after phagocytosis was estimated by the quantity of dichlorofluorescein diacetate converted to dichlorofluorescein intracellularly. Compared with results in samples from age- and sex-matched controls, PMNL and monocytes from HIV-1-infected patients exhibited a significantly increased capacity to phagocytose Staphylococcus aureus and Escherichia coli and generate reactive oxygen products. These results are consistent with the hypothesis that stimuli associated with early HIV-1 infection enhance the nonspecific response of phagocytic cells to potential bacterial pathogens. PMID- 8515134 TI - Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. The HIV Neurobehavioral Research Center Group. AB - As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1 associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system. PMID- 8515136 TI - Prevention of acute and chronic liver disease through immunization: hepatitis B and beyond. AB - Liver disease caused by hepatotrophic viruses imposes a substantial burden on health care resources. Persistent infections from hepatitis B virus (HBV), hepatitis C virus, and hepatitis delta virus result in chronic liver disease, while hepatitis A virus and hepatitis E virus produce a self-limited disease. Effective hepatitis B vaccines that provide long-term protection against chronic HBV infection have been available for > 10 years, while inactivated hepatitis A vaccines have recently been shown to prevent acute disease. To prevent transmission of HBV, scientifically and epidemiologically sound recommendations call for vaccination of all infants in successive birth cohorts worldwide. For hepatitis A vaccines, recommendations will be developed in the near future and should reflect vaccine performance and the epidemiology of hepatitis A. A number of policy, health care financing, and educational issues must be addressed to ensure the effective use of both of these vaccines. PMID- 8515138 TI - Guide to the use of hyperthermia equipment. 2. Microwave heating. The Japanese Society of Hyperthermic Oncology. PMID- 8515137 TI - Randomized trial of one versus two adjuvant hyperthermia treatments per week in patients with superficial tumours. AB - One test for thermotolerance development in a clinical situation is to evaluate the effects of altering the hyperthermia fractionation interval on tumour response to thermoradiotherapy. Between 1983 and 1990 44 evaluable advanced superficial tumours of miscellaneous origin in 41 patients were randomized to receive either once-weekly or twice-weekly external microwave hyperthermia treatments combined with radiation therapy. The mean age of patients was 62 years, and 85% had failed previous therapy. All lesions were less than 8 x 8 x 4 cm (L x W x D) and were heated by external 915 MHz microwaves. The mean radiation dose was 44 +/- 3 Gy (mean +/- SE) in the once-weekly group and 46 +/- 3 Gy in the twice-weekly group (p = 0.64). The mean volume of the lesions heated once weekly was 17 +/- 6 versus 23 +/- 5 cm3 for those heated twice weekly (p = 0.45). Hyperthermia was administered once weekly for 4.6 +/- 0.2 sessions (range 3-7) or twice weekly for 8.1 +/- 0.3 sessions (range 4-10). Thermometry was performed using 3.4 +/- 0.2 catheters and 5.1 +/- 0.6 thermal sensors per tumour in the once-weekly group, and 2.7 +/- 0.2 catheters and 5.8 +/- 0.3 thermal sensors per tumour in the twice-weekly group. Of the 44 evaluable randomized lesions a complete response (CR) at 2 months post-treatment was observed in 59% (13/22) heated once weekly and 55% (12/22) in those heated twice weekly. The prognostic factors predictive of tumour complete response were found by logistic regression analysis to be radiation dose and tumour volume, while the prognostic factors predictive of duration of response (Cox proportional hazards analysis) were median minimum tumour temperature (Tmin), minimum tumour temperature during the first heat treatment (Tmin1) and tumour volume. The duration of local control in lesions with Tmin < or = 39.5 degrees C was 11.7 +/- 1.9 months while for lesions with Tmin > 39.5 degrees C it was 23.0 +/- 4.2 months (p = 0.01). The ED50 was calculated by logistic regression to be 40 Gy (95% CI = 22-54 Gy) for once- and twice-weekly heated lesions. There was not a significant difference in tumour response or duration of response between populations randomized to receive once- versus twice-weekly hyperthermia treatments. There was also no difference in skin reaction rates between once- and twice-weekly hyperthermia treatments, nor could a correlation be found between any thermal parameter and skin reactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8515139 TI - Heat shock proteins (HSP-72 kd) in thermotolerant rat sciatic nerves. AB - Localized heating of the rat sciatic nerve over a length of 5 mm for 30 min at 43 degrees C resulted in the production of heat shock protein 72 kd in every nucleated cell and in the induction of thermotolerance in the heated area. HSP-72 kd was never detected in axons. Heat treatment (30 min, 45 degrees C) of thermotolerant nerves, 24 h after pretreatment, led to histopathological changes in the nerve, similar to those in non-thermotolerant nerves after a less strong treatment, i.e. heating for 30 min at 44 degrees C. Although axons did not contain HSPs after treatment at 43 degrees C, these structures tolerated treatment at 45 degrees C. Therefore we conclude that axons in the rat sciatic nerve are relatively heat-resistant and therefore we assume that axons do not need protection by HSPs; this is in contrast to endothelial cells and Schwann cells. Axons can be damaged indirectly as a consequence of vascular damage leading to ischaemia. Development of thermotolerance of the vasculature, ensuring a sufficient blood flow in the heated area, prevents this indirect damage. PMID- 8515141 TI - Thermal radiosensitization in two pairs of CHO wild-type and radiation-sensitive mutant cell lines. AB - Two pairs of Chinese hamster ovary cell lines, each comprising a parental normal responding and a radiation-sensitive mutant, were tested for their X-radiation sensitivity, hyperthermia sensitivity and thermal radiosensitization. The relative radiation responses were similar to those already published in the literature, indicating that the mutant cell lines, V-3 and 5-11, were extremely sensitive to radiation while their parental strains (AA8-4 and K1) exhibited normal sensitivity. The hyperthermia response of V3 was the same as that of the parental cell line AA8-4; the thermal sensitivity of 5-11 was greater than that of its parental line K1 but this difference decreased at higher temperatures (greater than 43 degrees C). These data indicate that the hyperthermia response and its targets are probably not related to the mutation-causing radiation sensitivity in the two pairs of parent-mutant cell lines. When heat and radiation were combined, the thermal enhancement of radiation sensitivity for different heat treatments was the same or larger in the mutant than in the parental cell lines. The mutants are known to be deficient in potentially lethal damage repair (PLDR), sublethal damage repair (SLDR) and repair of double-stranded DNA breaks; however, these deficiencies did not impair thermal radiosensitization, indicating that thermal radiosensitization may not be through these pathways in these particular mutants. In addition, the parental cell lines exhibited a significant sequence dependence of thermal radiosensitization (i.e. whether heat was applied before or after irradiation) at low survival levels (10(-4); this sequence dependence was very small to absent in the mutant cell lines at these survival levels. PMID- 8515140 TI - Whole-body hyperthermia combined with hyperfractionated irradiation of the thorax in dog: acute physiological response. AB - Whole-body hyperthermia has potential as an adjuvant treatment with chemotherapy and radiation therapy for diseases such as lung cancer which require both local and systemic control. The acute toxicity of whole-body hyperthermia combined with whole-thorax irradiation was studied in dogs. Twenty-eight dogs received three 2 h whole-body hyperthermia (WBH) treatments at 42.0 degrees C deep rectal temperature. Twenty-four of these dogs were also randomized to receive radiation doses of 18, 22.5, 27, 31.5, 40.5 or 45 Gy. Irradiation was given in 1.5 Gy fractions over 6 weeks. Three WBH treatments were given to 28 dogs with all dogs surviving treatment. WBH was given on days 1, 22 and 40 of the 6-week interval. Thirty-one dogs received radiation doses of 18-49.5 Gy without WBH. Deep rectal temperature was maintained at 41.9 +/- 0.3 degrees C over 2 h with an average of 20 min outside the chamber for irradiation. Two dogs required intervention with emergency medications during WBH treatment. One of the two dogs developed permanent neurological injury. Continuous physiological monitoring was necessary for successful WBH. WBH plus thoracic irradiation was well tolerated. All dogs survived all treatments. A significant but transient increase in peripheral blood leucocytes and a decrease in platelet counts occurred after each WBH treatment. The addition of thoracic irradiation up to 45 Gy in 1.5 Gy fractions did not appear to alter the acute toxicity of WBH with the exception of an increase in the protein content of lung lavage fluids. In conclusion, multiple WBH treatments of 2 h at a target temperature of 42 degrees C in addition to thoracic irradiation up to 45 Gy in 1.5 Gy fractions was administered with only mild acute toxicities occurring. Core temperature could be maintained for up to 20 min outside of the WBH chamber which allowed irradiation to be given concurrently with hyperthermia at a core temperature of 42 degrees C +/- 0.1 degree C. PMID- 8515142 TI - Effect of hyperthermia on rhodamine 123 cytotoxicity in doxorubicin-sensitive and doxorubicin-resistant human breast carcinoma cell lines in vitro. AB - Rhodamine 123 (Rh123) cytotoxicity and intracellular accumulation were studied in normothermic and hyperthermic conditions in a human breast carcinoma cell line (MCF7/WT) and its doxorubicin-resistant subline (MCF7/DoxR). MCF7/DoxR cells were resistant to hyperthermia and Rh123. Hyperthermic potentiation of Rh123 cytotoxicity was present in MCF7/WT but not in MCF7/DoxR cells. Results suggest that the effect observed in MCF7/WT cells is related to a heat-induced increased accumulation of Rh123 and not to a heat-induced activation of the drug. A low basal uptake and a fast release of Rh123 could explain the resistance of MCF7/DoxR to the drug. Resistance to Rh123 and lack of a heat-induced increased uptake account for the lack of hyperthermic enhancement of Rh123 cytotoxicity in the resistant cells. PMID- 8515143 TI - Increased uptake and prolonged retention of actinomycin D by concomitant hyperthermia related to cytotoxic enhancement. AB - We investigated the possible mechanisms of hyperthermic enhancement of actinomycin D (AMD) cytotoxicity in a neoplastic cell line. The hyperthermic enhancement of AMD cytotoxicity depended on both the temperature and the sequence of the administration. The percentage survival of simultaneous treatment of either 42 or 43 degrees C hyperthermia with 5 micrograms/ml AMD was 42% or 2.2%, respectively, and the amount of AMD in the DNA (DNA-bound AMD) of simultaneous hyperthermia at either 42 or 43 degrees C was 16.5 or 27.2 ng/10(6) cells, respectively. The percentage survival of sequential treatment of 5 micrograms/ml AMD following either 42 or 43 degrees C hyperthermia was 55 or 46%, respectively. The amount of DNA-bound AMD of sequential hyperthermia at either 42 or 43 degrees C was 10.8 or 21.7 ng/10(6) cells, respectively. In addition, the percentage survivals of the S-phase and G1-phase cells concomitantly treated with 43 degrees C hyperthermia and 5 micrograms/ml of AMD were 1.4 and 92%, respectively, and the amounts of DNA-bound AMD of these S-phase and G1-phase cells were 28.2 and 1.6 ng/10(6) cells. These findings suggested that an increased amount of AMD in DNA was responsible for the hyperthermic enhancement of AMD cytotoxicity. When the G1 phase cells were treated with 5 micrograms/ml AMD alone, without hyperthermia, the amount of AMD in acid-soluble fraction of the G1-phase cells was quite low (0.3 ng/10(6) cells). However, concomitant hyperthermia treatment with AMD at the G1-phase significantly increased the AMD amount (1.6 ng/10(6) cells at 42 degrees C, and 3.1 ng/10(6) cells at 43 degrees C) up to a level equal to that in asynchronous (1.7 ng/10(6) cells) and S-phase cells (2.1 ng/10(6) cells) simultaneously treated with hyperthermia and AMD. It was suggested that hyperthermia altered the membrane permeability of the G1-phase cells. The increase of the AMD amount in the DNA might thus be the result of higher intracellular drug concentration. PMID- 8515145 TI - 915 MHz microwave interstitial hyperthermia. Part I: Theoretical and experimental aspects with temperature control by multifrequency radiometry. AB - Microwave interstitial hyperthermia now plays an increasing part in the various hyperthermia techniques used in cancer treatment. This paper will present the design, construction and theoretical as well as experimental study of miniature coaxial antennas designed to heat tumours of various volumes and sizes. Monitoring temperature using multifrequency radiometry during hyperthermia stems naturally from the very design of these antennas. Experiments on phantoms, animals and patients in phase I clinical assessment have demonstrated that microwave interstitial hyperthermia can be achieved with temperature control and monitoring by microwave radiometry. PMID- 8515144 TI - Non-invasive microwave multifrequency radiometry used in microwave hyperthermia for bidimensional reconstruction of temperature patterns. AB - Microwave radiometry, used routinely since 1984 for non-invasive temperature measurements during hyperthermia sessions for superficial tumours treatment has proven its efficiency for temperature control. From radiometric temperature measurements in two frequency ranges (around 1 and 3 GHz) and superficial (or cutaneous) temperature measurements achieved during hyperthermia sessions, a numerical method to obtain the two-dimensional thermal profile has been developed and implemented. This method is based on hyperthermia simulation from the bioheat equation, the absorbed microwave power calculation in the medium taking into account the radiative diagram of the applicator, and the calculation of radiometric temperatures. From these experimental measurements (radiometric and superficial temperatures, heating power, dielectric and thermal characteristics), a program to determine the bidimensional distribution of temperature during the hyperthermia session has been developed, tested and used during and after clinical treatments. PMID- 8515146 TI - 915 MHz microwave interstitial hyperthermia. Part II: Array of phase-monitored antennas. AB - In order to heat the whole volume of a tumour by microwave interstitial hyperthermia it is necessary to use an antenna array. The antenna modelization and the numerical solution of the bidimensional bioheat transfer equation allow determination of temperature evolution during a heating session. The calculations are taken for four antennas fed in phase and the theory is then proven by experiments on gel and on patients. Results are presented on cross-section heating patterns and their time evolution. Temperature distribution is calculated when feeding one antenna by a feeding current out of phase with the other currents. The phase difference value is optimized and it is then demonstrated that the heated volume is increased by successively feeding each antenna with an out-of-phase current. The time taken to feed each antenna one after the other is optimized. PMID- 8515148 TI - Theoretical and experimental investigations of a newly developed intracavitary applicator system for the radiothermotherapy of gynaecological tumours. AB - This paper describes a new type of applicator system for the intracavitary radiothermotherapy of gynaecological tumours. Hyperthermia and radiation can be delivered by one and the same applicator. The hyperthermia is delivered by a modified capacitive heating technique (27.12 MHz) combined with cooling systems, the radiation by the numerically controlled oscillation of a gamma source on the inside of the main applicator, the RF gamma applicator (HDR afterloading technique). Isotherms and isodoses can be adapted to the anatomical-pathological situation. Interactions between the applicator system and the surrounding tissue were investigated in a theoretical model (FEM). Complex two-dimensional SAR calculations as well as three-dimensional temperature calculations were carried out. The RF gamma applicator was also examined by thermography; the thermography proved the theoretical modelling to be correct. The applicators were also tested in animal experiments. PMID- 8515147 TI - 915 MHz microwave interstitial hyperthermia. Part III: Phase II clinical results. AB - From October 1989 to October 1991, 16 patients (17 tumours) with locally advanced carcinomas of the oral tongue and eight patients with second carcinomas of the base of tongue in previously irradiated areas, have been treated by means of an interstitial hyperthermia-brachytherapy combination in a phase II clinical trial. Each miniature microwave antenna of our hyperthermia system, called HIMCAR, is used both for heating and for thermal measurements by microwave radiometry at 3 and 9 GHz (see Part I). Among these 25 lesions (21 T2, 4 T3), 21 showed a complete response (15/17 locally advanced carcinomas and 6/8 second carcinomas in previously irradiated areas). The toxicity was not severe (less than 10%). A French multicentre phase III study is now under way. PMID- 8515149 TI - Automation of temperature control for large-array microwave surface applicators. AB - An adaptive temperature control system has been developed for the microstrip antenna array applicators used for large area superficial hyperthermia. A recursive algorithm which allows rapid power updating even for large antenna arrays and accounts for coupling between neighbouring antennas has been developed, based on a first-order difference equation model. Surface temperatures from the centre of each antenna element are the primary feedback information. Also used are temperatures from additional surface probes placed within the treatment field to protect locations vulnerable to excessive temperatures. In addition, temperatures at depth are observed by mappers and utilized to restrain power to reduce treatment-related complications. Experiments on a tissue equivalent phantom capable of dynamic differential cooling have successfully verified this temperature control system. The results with the 25 (5 x 5) antenna array have demonstrated that during dynamic water cooling changes and other experimentally simulated disturbances, the controlled temperatures converge to desired temperature patterns with a precision close to the resolution of the thermometry system (0.1 degree C). PMID- 8515150 TI - [Surgical aspects of automatic implantable cardioverter defibrillator (AICD) in patients with life-threatening ventricular tachyarrhythmias]. AB - Implantations of automatic implantable cardioverter defibrillator were performed in five patients with life-threatening ventricular tachyarrhythmias. Preoperative diagnoses of arrhythmias were sustained ventricular tachycardia (VT) in two cases, ventricular fibrillation (VF) in two cases and sustained VT+VF in one case. Four of five cases had basic diseases respectively (broad anterior myocardial infarction, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy), and the other case was idiopathic. Preoperative CTR were 43-65% (mean 57.4%) and left ventricular ejection fraction were 26-76% (mean 51.2%). Implantation of AICD was indicated for patients who survived circulatory arrest or life-threatening VT. Median sternotomy (3) or left antero-lateral thoracotomy (2) were performed for implantation of large-small patch electrodes for defibrillation. AICD generators were implanted in the pocket under abdominal rectal muscle in all cases. Postoperatively myocardial insufficiency, pericarditis, pleuritis occurred in three cases respectively. In the follow-up periods (2-25 months, mean 13 months), AICD worked effectively in two patients with spontaneous VT (6 months, 1 year after operation) and no cardiac death was experienced. We concluded that AICD system is effective for the life-threatening ventricular tachyarrhythmias, although the further estimation in longer follow-up periods are warranted. PMID- 8515151 TI - [Changes of alpha hANP concentration in arterial and coronary sinus blood during and after cardiopulmonary bypass]. AB - Recent studies suggest that plasma levels of alpha-hANP may reflect the severity of heart failure, but mechanism whereby ANP secretion increase is not known. Changes in alpha-hANP concentration in the arterial (A-ANP) and coronary sinus blood (CS-ANP) during and after the cardiopulmonary bypass (CPB) were measured to investigate the role of ANP in patients undergoing cardiac surgery. Fifteen patients were divided into 2 group; Group I, valvular heart disease (n = 9), Group II, coronary artery disease (n = 6). Both A-ANP and CS-ANP were significantly higher in the Group I than Group II before and during CPB. The difference between two groups decreased and was insignificant after CPB. The CS ANP was twice as high as A-ANP at simultaneous sampling point. Significant correlations between the changes in PCWP (delta PCWP) and delta A-ANP (p < 0.01), delta RAP and delta A-ANP (p < 0.02) and an inverse linear correlation between CI and A-ANP (p < 0.01) were observed. Not a significant correlation was found between ANP and urine volume, urinary sodium excretion and other renal functional parameters during and after CPB. Hypothermia and the use of mannitol in large quantities were considered to be factors. In the Group I, A-ANPs were also measured in the postoperative follow-up period. A-ANP remained elevated above 100 pg/ml in patients with poor and decreased below 100 pg/ml with good prognostic signs 3 to 6 months postoperatively. From these results, it is suggested that alpha hANP is secreted from the atrial wall to the coronary sinus vein and the levels of alpha-hANP in the perioperative and follow-up period after heart surgery, especially in the valvular heart disease, are considered to reflect the cardiac performance. PMID- 8515152 TI - [Right ventricular assist for experimental acute right ventricular failure in dogs]. AB - In order to assess the efficacy and the problems of right ventricular (RV) assist in supporting the failing RV, we analyzed the influence of RV assist on pulmonary circulation, respiratory function and left ventricular (LV) function in dogs. Thirty healthy mongrel dogs were anesthetized with thiopental sodium. The animals were intubated and ventilated with 100% oxygen. Tidal volume was 15 ml/kg at a rate of 20 per minute. RV failure was produced by ligation of the right coronary artery at its origin and the mid-portion. Tricuspid regurgitation was induced by tearing the chordae tendineae with a specially made knife, while 5M-NaOH was injected into the RV free wall. Then, RV support was initiated by placing a drainage cannula in the right atrium and a perfusion cannula in the pulmonary artery trunk. The RV assist was done with a diaphragm type pneumatic pump, which worked in ECG asynchronous mode (% systole:40%, 100 beats per minute). Animals were divided into three groups according to RV assist rate; Group I: 30% (n = 10), Group II: 60% (n = 10), Group III: 100% (n = 10). Hemodynamics were observed for five hours and measured once an hour. Hemodynamically, there were no significant differences in mean right atrial pressure, pulmonary artery pressure or aortic pressure at any time for the three groups. In terms of net infiltration pressure, given by the formula, pulmonary microvascular pressure minus colloid osmotic pressure, a significant difference appeared early, at the 1st hour, between Groups I and III (P < 0.01), and lasted until the 5th hour. Alveolar arterial oxygen differences were highest in Group III and lowest in Group I throughout most of the experiment. Early on, at the 1st hour, a significant difference of Alveolar-arterial oxygen difference developed between Groups I and III (p < 0.01) and at the 2nd hour a significant difference was also seen between Groups II and III (p < 0.05). Extravascular lung water was 8.9 +/- 2.2 ml/kg at the 5th hour in Group III, which was significantly higher than that in Groups I and II (p < 0.01), which were 6.1 +/- 1.3 and 6.1 +/- 1.1 ml/kg. LV max. dp/dt at the 5th hour in Group III was significantly lower than that in Groups I and II (p < 0.05). Postmortem histopathologic examination showed a high degree of perivascular cuffing in Group III, slight cuffing in Group II, and almost none in Group I and the control group. There was no alveolar flooding in any group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8515153 TI - [The protective effect of continuous retrograde cerebral perfusion on the central nervous system during deep hypothermic systemic circulatory arrest]. AB - Deep hypothermic circulatory arrest (DHCA) was introduced as an adjunct for operations involving aortic arch lesions in 1970's and has since been widely used. Profound hypothermia protects the brain and other vital organs by reducing metabolic rate. We initiated the use of continuous retrograde cerebral perfusion (CRCP) via the superior vena cava during DHCA in 1987. We studied 15 patients who required DHCA and CRCP during repair or replacement of the aortic arch. CRCP times ranged from 11 to 78 (mean +/- S.D.; 37.3 +/- 21) minutes, and minimal nasopharyngeal temperatures ranged from 13.7 to 25 (17.7 +/- 2.6) degrees C. Two patients died one month postoperatively due to preoperative disease. Three patients, who were in shock preoperatively due to cardiac tamponade, developed acute renal failure postoperatively. The remaining patients were weaned from the respirator by the 2nd postoperative day. No patient had CRCP-related complications. During CRCP, the partial pressure of oxygen (PO2), saturation of oxygen (SO2), and oxygen content significantly decreased (p < 0.001), and the partial pressure of carbon dioxide (PCO2) and CO2 content significantly increased (p < 0.001) between retrogradely perfused blood and blood draining from the arch vessels. These results most probably reflected that the aerobic metabolism of the brain was maintained by CRCP while the central nervous system was maintained in a hypothermic state, with oxygen and substrate availability, wash-out of metabolites, and buffering capacity and oncotic pressure of the blood maintained. This technique offers the potentials of sufficient metabolic support to the brain during DHCA and prolonged safe time limits of DHCA. PMID- 8515154 TI - [Growth of the pulmonary arteries and morphological assessment after Blalock Taussig shunts]. AB - Clinical and angiographic results were studied after 121 classic Blalock-Taussig shunts (CBT) and 74 modified Blalock-Taussig shunts (MBT) with polytetrafluoroethylene grafts. 1. The actuarial shunt patency rate in all 195 patients showed a significant difference in patency between CBT and MBT at six months after operation. (CBT = 91.6%, MBT = 98.6%, p < 0.05). The patency rate of 4-mm MBT grafts was lower than that of CBT of grafts. 2. The 109 patients who underwent postoperative angiography were evaluated for morphological features of anastomosis. The incidence of pulmonary arterial stenosis caused by anastomosis was 15.3% with CBT and 18.9% with MBT; these values were not significantly different. The primary characteristic of CBT anastomosis was a funnel-shaped stenosis at the side of shunt vessel, but this feature did not disturb pulmonary artery growth. In contrast, MBT grafts sometimes narrowed along their entire length, causing deterioration of pulmonary artery growth. 3. The 60 patients in whom pre- and post-operative pulmonary artery sizes were able to be evaluated were studied for pulmonary artery growth. The development ratio (DR) was calculated as the ratio of postoperative to preoperative pulmonary artery index (post-PAI/pre-PAI). a) DR in patients with lower preoperative PAI was greater than that in patients with higher preoperative PAI. b) DR in patients under the age of 6 months was greater than that in older patients. c) There were no significant differences in DR between CBT and MBT or between pulmonary stenosis and pulmonary atresia. d) Relative to the BT shunt, the ipsilateral pulmonary artery grew to the same degree as the contralateral artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515155 TI - [Late results of aortic valve plasty (aortic leaflet slicing) simultaneously performed with mitral valve surgery]. AB - We followed the course of 20 patients who underwent aortic valve plasty (AVP) combined with mitral valve surgery for rheumatic mild aortic valve disease in association with severe mitral valve disease. At operation, all patients underwent aortic leaflet slicing with a knife, and aortic commissurotomy were performed additionally in 10 patients. After surgery, the degree of aortic valve regurgitation and the amplitude of aortic leaflet motion were assessed chronologically, using ultrasound cardiography. One month after surgery, all but one patients showed a reduction in regurgitation to degree I or less. From the third post-operative year, however aortic valve regurgitation tended to increase again. However, the post-operative degree of regurgitation was observed not to be severer than the pre-operative degree of regurgitation, and no patients showed aggravation of aortic valve regurgitation attributable to exacerbation of mitral valve disease. We divided the patients into two groups according to improvement of aortic valve regurgitation. In the group where the degree of regurgitation returned to the pre-operative one, the degree of amplitude of leaflet motion began to reduce from the third post-operative year and was nearly equal to the pre-operative one at the fifth post-operative year. The results of this study can be summarized as follows: 1. From the third post-operative year, aortic regurgitation was aggravated and aortic valve motion amplitude decreased. 2. The number of sliced valve leaflets and incised commissures did not correlate well with the post-operative reduction in regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515156 TI - [Definitive repair for double inlet ventricle and common atrio-ventricular valve]. AB - From 1982 through 1990, 13 patients with double inlet ventricle and common atrio ventricular valve underwent definitive cardiac surgery. Nine patients simultaneously had anomalous systemic venous connection and 4 had anomalous pulmonary venous connection. One patient with double inlet left ventricle underwent a successful partition of ventricle and atrio-ventricular valve. All other 12 patients underwent a Fontan operation, which utilized different techniques to deal with various forms of anomalous systemic and pulmonary venous connection. Four patients with common atrioventricular valve regurgitation underwent a Fontan operation combined with a concomitant circular annuloplasty of atrio-ventricular valve. In all 4 patients, the degree of regurgitation decreased postoperatively. There was one operative death (mortality 7.7%). Most of patients with double inlet ventricle and common atrio-ventricular valve now are considered to be suitable not for partition but for the Fontan operation. Because of the complexity of anatomic variables, however, the repair of anomalous systemic or pulmonary venous connections in conjunction with the Fontan operation requires an individualised plan in each patient to provide unobstructed systemic and pulmonary venous pathways. We think that a circular annuloplasty could effectively decrease the degree of atrio-ventricular valve regurgitation in most cases. PMID- 8515157 TI - [Histological study of saphenous vein graft disease after coronary artery bypass grafting]. AB - In an attempt to determine the cause of pathological changes in saphenous vein grafts arising months or years after coronary artery bypass surgery, we studied 13 patients who underwent reoperation 7 months to 12 years after the first surgery. Four of 17 grafts occluded early in the postoperative period. In these four cases, only thrombosis was observed in the graft lumen, and there were no marked changes in the graft wall. The 13 grafts occluded in late postoperative period exhibited two significant pathological changes. One was fibrointimal proliferation, which was found to some extent in all 13 grafts. However, it was thought to be the cause of occlusion in only one case. This fibrointimal proliferation was interpreted as a remodeling process associated with arterialization of the vein graft and occasionally causing graft occlusion. The other long-term pathological change, observed in 11 grafts, was atherosclerosis. Atherosclerotic changes significantly contributed to the development of occlusive and stenotic lesions and are suspected to be a major cause of late saphenous vein graft deterioration. In conclusion, fibrointimal proliferation and atherosclerosis are different pathological process, and it is important to distinguish between them in the evaluation of saphenous vein graft disease. PMID- 8515158 TI - [Coronary artery bypass grafting surgery without cardiopulmonary bypass]. AB - Improved technique in coronary artery surgery has allowed coronary artery bypass graftings (CABG) to be placed on beating heart. The effects of extracorporeal circulation and cardiac arrest are eliminated. From Jan. 1991 to June, 1992, we performed CABG surgery without cardiopulmonary bypass and cardiac arrest in 15 patients; the age ranged from 47 to 82 years with the mean of 65. Patients who had LAD and/or RCA stenosis were candidate of this procedure in early series. However in recent series, we extended the candidate to three-vessel or LMT stenosis cases who were considered ineligible for standard CABG because of renal failure or poor left ventricular function. Distal anastomoses were performed with interruption of coronary flow. From one to two distal anastomosis to the LAD and/or RCA (mean 1.4/patient) were performed. The ITA was used in all 15 patients. Combined cardiac or vascular operation was performed in 5 patients (AAA repair, TAA repair, carotid endarterectomy or coronary endarterectomy). There were no deaths and no perioperative myocardial infarction. Postoperative angiography were performed in 12 patients with a patency rate of 89%. PMID- 8515159 TI - [Diagnosis of mediastinal neoplasms using mediastinoscopy and CT-guided needle biopsy supported by gene analysis]. AB - Of 140 cases of mediastinal neoplasms in our hospital, histological diagnosis was confirmed in 129 cases. We examined the methods of preoperative biopsy with those 129 cases. Biopsy had been performed in 25 cases. Mediastinoscopy was performed in seven cases, needle biopsy in eight cases, lymph node biopsy in eight cases, esophageal biopsy using a gastrofiberscope in one case, transbronchial biopsy using a bronchoscope in one case. The true positive rates of those methods were 100% for both mediastinoscopy and lymph node biopsy, and 75% for needle biopsy. Preoperative misdiagnosis occurred in two cases of needle biopsy. The postoperative histological diagnosis was malignant lymphoma in both cases. We performed gene analysis of the immunoglobulin heavy chain gene, light chain kappa and lambda genes, and the T-cell receptor beta gene by use of biopsied specimens, and we found rearrangement bands of these genes in the cases of malignant lymphoma. Therefore, we summarize that gene analysis is a reliable method if malignant lymphoma is suspected. If a needle biopsy is performed under CT guidance, the needle is sure to puncture the tumor. We concluded, therefore, that if a tumor is located in the anterior mediastinum, CT-guided needle biopsy should be performed first of all. Mediastinoscopy is a useful method if the tumor is located in the mid-mediastinum. PMID- 8515160 TI - [Surgical treatment of patent ductus arteriosus in the adult]. AB - Ten patients over the age of 30 were operated on for isolated patent ductus arteriosus (PDA). Division was performed in 9 patients and ligation in only one. In two cases, the aorta had to be cross-clamped above and below the level of the ductus under normothermia because of massive bleeding. In another two patients with aneurysmal dilatation and calcification of the aortic side of the ductus, PDA was closed by aortic cross-clamping under LA-to-femoral-artery bypass with a centrifugal pump. Postoperatively, all patients are well and in NYHA class I. Therefore, in the adult, if the conventional method of division between ductus clamps is considered dangerous due to increased friability and atheromatous changes of the ductus and surrounding tissues, the ductus should be closed during aortic cross-clamping under assist circulation. In such a case, LA bypass is considered quite useful and safe. PMID- 8515161 TI - [Surgical analysis for metastatic lung tumor originating from renal cell carcinoma]. AB - In this study, we evaluated 16 surgically treated cases of metastatic lung tumors originating from renal cell carcinoma. Ten males and 6 females with ages ranging from 31 years to 74 years (average 60.8 years) were examined. Five cases had solitary metastasis, 4 had ipsilateral multiple metastasis, and 7 had bilateral metastasis. The average number of lung metastatic legion was 3.3. Disease free intervals ranged from 0 to 120 months (average 22.6 months). Tumor doubling time calculated in only 8 cases, ranged from 36 to 510 days (average 126 days). In 8 cases, tumor doubling time could not be calculated because tumor growth was too slow. Partial resection or segmental resection was performed in 14 cases, 8 with ipsilateral and 6 with bilateral lung metastasis. Lobectomy was performed in only two cases. Five year survival rate was 43% as determined by the Kaplan-Meier method. We believe that such cases possessing a slow tumor growth rate have a better survival rate. PMID- 8515162 TI - [Changes in cardiorespiratory function after radical esophagectomy by bilateral thoracotomy approach in dogs]. AB - Eighteen dogs (8-21 kg) were anesthetized with pentobarbital sodium, buprenorphine and pancuronium bromide followed by endotracheal intubation in the supine position. Eighteen dogs were divided into two groups. Group 1 (n = 9) underwent thoracic esophagectomy with regional lymph nodes dissection under the right thoracotomy. Group 2 (n = 9) underwent the same manner of Group 1, and then left thoracotomy was additionally performed in the 5th intercostal space to completely dissect the left side mediastinal lymph nodes. During surgical procedure, lactated Ringer's solution (L-R) were continuously administered and Dextran 40 were given according to surgical bleeding. For postoperative fluid therapy, L-R were given at 4 ml/kg/hr under spontaneous breathing. Central venous pressure (CVP), pulmonary arterial pressure (PAP), pulmonary wedge pressure (PWP), mean arterial pressure (AP), heart rate (PR), cardiac output (CO), extravascular lung water (EVLW), blood gas, lung resistance (RL), dynamic lung compliance (CL) and colloid osmotic pressure (COP) were measured at preoperative phase and three days after surgery. Significant differences were found in the PaO2, Qs/Qt, respiratory index (RI) and the dosage of Dextran 40 between Group 1 and Group 2. There are no significant differences in the tracheal ischemic changes between the two groups, but peripheral atelectasis in Group 2 seemed to be severe as compared to that in Group 1. From these results, extended radical esophagectomy by bilateral thoracotomy approach for clinical cases seems to be possible under the exact indication and intensive perioperative care. PMID- 8515163 TI - [Surgical treatment of total left anomalous pulmonary venous connection to the coronary sinus without atrial septal defect]. AB - Surgical repair of total left anomalous pulmonary venous connection to coronary sinus without atrial septal defect (ASD), a very rare situation, was recently conducted. A 13-year-old girl was diagnosed as ASD. Two-dimensional echocardiography, however, indicated enlarged coronary sinus preoperatively. During operation the absence of ASD and drainage of total left pulmonary veins into the coronary sinus were observed. The operation was conducted by the method of Van-Praagh. The coronary sinus was closed to divert pulmonary venous blood to the left atrium, while maintaining coronary venous return to the right atrium. The postoperative course was uneventful and cardiac catheterization showed satisfactory results. PMID- 8515164 TI - [Surgical treatment of ruptured sinus of Valsalva aneurysm]. AB - We operated on 3 patients with ruptured sinus of Valsalva aneurysm (RSVA). According to the classification by Konno, 2 of them had type I RSVA where aneurysm originated from the right coronary sinus rupturing into the right ventricle, and another type IV where it arose from the non-coronary sinus draining into the right atrium. Both of the 2 with type I RSVA had accompanied ventricular septal defect (VSD) of Kirklin type I. One of them had infective endocarditis with vegetations clinging to the aortic valve, the pulmonary valve and the right ventricular wall adjacent to VSD, and aortic regurgitation of grade II consequently occurred. In this patient, the aortic cusps and the wall of sinus of Valsalva aneurysm were taken out with vegetations. The defect of sinus and VSD were closed with one large patch and a 25 mm SJM aortic valve was implanted using the patch as a part of annulus. The other patient with type I RSVA received a direct closure of defect of Valsalva sinus and VSD. Another patient with type IV RSVA underwent a direct closure of right atrial wall where aneurysm protruded. All 3 patients are doing well without shunt and aortic regurgitation. In this paper, diagnosis, surgical treatment and outcome of RSVA were reviewed. PMID- 8515165 TI - [One-staged operation for funnel chest, mitral regurgitation and annulo-aortic ectasia associated of Marfan's syndrome]. AB - One-staged operation was successfully performed in a 23-year-old female with funnel chest, mitral regurgitation and annulo aortic ectasia secondary to Marfan's syndrome. A midline skin incision was made and the sternum and costal cartilages were mobilized for sternal turnover with rectus muscles pedicle. This procedure offered an excellent operative field, even though the heart and aneurysmal ascending aorta were displaced into the left hemithorax. The combined superior-transseptal approach to the left atrium was used to perform mitral valve replacement. This approach also provided an excellent exposure of the mitral valve. Cabrol's operation was done for annulo aortic ectasia. Our concepts for the operation of open heart surgery complicated with severe funnel chest were discussed. PMID- 8515166 TI - [A successful operation of isolated levocardia with left atrial isomerism, polysplenia and tetralogy of Fallot]. AB - A four-year-old boy who had isolated levocardia associated with left atrial isomerism, polysplenia and tetralogy of Fallot underwent successful corrective surgery. In addition, these anomalies were complicated by interrupted inferior vena cava, azygos continuation, and total anomalous hepatic venous connection. Because of these systemic venous anomalies, cardiopulmonary bypass presented us some problems of venous cannulations. We used 4 direct venous cannulations; i.e., superior vena cava, persistent left superior vena cava through coronary sinus, azygos vein and hepatic vein. Reports of total correction in patients with isolated levocardia associated with tetralogy of Fallot are rare, and we report the case with some reviews of the related literature. PMID- 8515167 TI - [Surgical treatment of left atrial myxoma with concomitant acquired heart disease]. AB - Among 21 patients with left atrial myxoma treated during the past 11 years in our institute, 3 patients had associated acquired heart disease which required concomitant cardiac surgery. Two patients had atherosclerotic coronary arterial disease, and underwent single coronary artery bypass grafting (CABG) and 4 CABGs in addition to removal of myxoma, respectively. Both of them received CABGs after removal of myxoma, because the intraoperative heart protection using retrograde coronary perfusion could afford the situation. Another patient had a huge left atrial myxoma associated with mitral and tricuspid regurgitation. She suffered from sudden heart failure caused by tumor obstruction of blood flow across the mitral valve, and an emergency surgery was performed. She underwent mitral valve replacement for annular dilatation with prolapse of both leaflets and tricuspid annuloplasty for annular dilatation, in addition to removal of myxoma. All of these 3 patients went a good postoperative course and are doing well now with no local recurrence. In this paper, preoperative and intraoperative evaluation, and surgical treatment of associated heart disease with left atrial myxoma were discussed. PMID- 8515168 TI - [A case of surgery for AAE with dissection extended to right coronary artery- device for reconstruction of coronary artery and retrograde cardioplegia and retrograde cerebral perfusion]. AB - We experienced a surgical case of aortic dissection (Stanford type A) with annuloaortic ectasia in Marfan Syndrome. A 45-year-old female who had been diagnosed as Marfan Syndrome three years age was emergently admitted to our hospital with sudden chest pain. We diagnosed this case as aortic dissection of Stanford type A by ultrasonic cardiogram and thoracic CT. The ascending aorta was replaced with composite graft by modified Bentall procedure, right coronary artery was bypass to segment 2 using vein graft and left coronary artery was interposed by Dacron graft. During operation we utilized retrograde cold blood cardioplegia for cardiac arrest (180 min.) and retrograde cerebral perfusion accompanied with total circulatory arrest (45 min.). No complication such as cardiac damage and cerebral damage was found postoperatively. We discussed surgical method for aortic dissection with anuloaortic ectasia in particular reconstruction of coronary artery, cardioplegia and cerebral protection. PMID- 8515169 TI - [A case report of tracheal inflammatory pseudotumor]. AB - The tracheal tumor is uncommon, and tracheal inflammatory pseudotumor seems to be rare with only four cases reported in the Japanese literature. We here in report a case of tracheal inflammatory pseudotumor in a 61-year-old Japanese man presenting with dyspnea and wheezing 2 weeks after a sub total gastrectomy Billroth I for gastric cancer in april 1991. At bronchofiberscopic examination a rounded tracheal mass 40 mm distal to the vocal cord was found. High vascular on the surface and obstruction of about 90% of the tracheal lumen was noticed. Surgery was attempted immediately and 25 mm of the trachea was excised. The histopathological findings revealed an inflammatory pseudotumor. We concluded that the tumor was caused by injury during tracheal intubation. PMID- 8515171 TI - [A case of modified Fontan procedure for SLL single ventricular heart with bicaval total occlusion]. AB - We successfully performed a modified Fontan procedure and bidirectional Glenn shunt for a 6-year-old boy with single ventricular heart (SLL). After the operation, the patient suffered from a severe pneumonia, so intravenous catheter had to be inserted for a long time. Post operative angiography revealed bicaval total occlusion. But, inspite of these several complications, this patient is doing well. We believe that if bilateral SVC without communication exist on such a candidate for the Fontan type procedure, LSVC should be anastomosed to PA. The bidirectional Glenn shunt will contribute to save a life of the patient when the systemic venous route was occluded. In addition, the anticoagulation therapy should be taken for the patients underwent the Fontan type procedure. PMID- 8515170 TI - [Continuous irrigation followed by combined omental transposition and pectral muscle rotation for treatment of postoperative mediastinitis with DIC in a child]. AB - A 8-year-old boy was complicated with mediastinitis with DIC 20 days after replacement of the stenotic right ventricular outflow conduit. Open drainage and debridement were performed and semi-closed continuous irrigation with 1% povidone iodine was continued for 10 days to control DIC. Thereafter, the pedicled omentum was mobilized to the upper anterior mediastinum, however, it was too thin to obliterate there. To obliterate the upper anterior mediastinum and cover the infected graft, the major pectoral muscle flap was introduced to the anterior mediastinum through the window created by removing a part of left second rib. The sternum was closed primarily. The postoperative course has been well and no recurrence has been proved for 1 year. PMID- 8515172 TI - [A case report of mediastinal teratoma complicated with cardiac tamponade]. AB - A 10-year-old Japanese boy was admitted to our hospital with complaints of the sudden and severe chest pain having occurred when he caught a ball on his chest. A chest X-ray film and MRI made a diagnosis of cardiac tamponade caused by perforation into the pericardial sac of a mediastinal teratoma and pericardial drainage was carried out. Pericardial effusion showed cloudy yellow and CA 19-9 level in the effusion was 6, 538.2 U/ml. The tumor was extirpated after recovery of his general condition. The tumor was consisted of solid material (5 x 6 x 3 cm) and of cystic part (4 x 6 x 0.8 cm) involving of viscous yellowish fluid. Microscopic sections showed ulcer with bleeding, granulation and pancreatic tissue. Histopathological diagnosis was benign mature teratoma. Including this case, fourteen cases of mediastinal teratomas with cardiac tamponade have been reported and this is the youngest case. Pancreatic tissue were observed histopathologically in most cases and it was thought that autodigestion by digestive enzyme from pancreas was major cause of perforation of the tumor into the pericardial sac. PMID- 8515173 TI - [Surgical repair of aortico-left ventricular tunnel, a case report]. AB - Aortico-left ventricular tunnel is an extremely rare congenital heart disease. Although there are dozens of English-written literature about this condition, we could not find any report in Japanese. Our patient was a boy whose illness was diagnosed as aortico-left ventricular tunnel when he was three years old. Soon after the diagnosis was made he underwent surgical correction. The orifice of tunnel was closed using EPTFE patch at the aortic side and at the left ventricular side was closed directly. Postoperatively moderate degree of aortic valvular regurgitation was remained. Three years after the surgical correction, now the boy is six years old and doing well. But we anticipate that he man need aortic valve replacement in the near future. PMID- 8515174 TI - [Left atrial free-floating ball thrombus in a patient without mitral valve disease]. AB - A free-floating ball thrombus in the left atrium is a rare clinical problem with potentially catastrophic consequences. Thus, early diagnosis and prompt surgical intervention are mandatory. This report dealt with a free-floating ball thrombus in the left atrium in a case without mitral valve disease. A 82-year-old woman was presented with dyspnea, hypotension, and fever. On admission she had cardiac arrhythmia, but had no cardiac murmur. The electrocardiogram revealed atrial fibrillation. Chest X-ray examination showed marked cardiomegaly (cardio-thoracic rate; 94%) without evidence of pulmonary venous congestion. Coagulation studies revealed decreased coagulability. Transthoracic and transesophageal echocardiograms showed retention of pericardial effusion, and a free-floating ball thrombus in the dilated left atrium. Thickening, calcification, and restricted motion of the mitral leaflets were not observed by echocardiography. Removal of the free-floating ball thrombus in the left atrium was successfully performed on the emergency basis. The intact mitral valve was also confirmed at operation. The patient recovered uneventfully. Usefulness of echocardiography, particularly transesophageal echocardiography, for precise diagnosis and intraoperative management of a free-floating ball thrombus in the left atrium is discussed. PMID- 8515175 TI - [Usefulness of expandable metallic stent to bronchial stenosis caused by an advanced lung cancer--a case report]. AB - We used Expandable Metallic Stent (EMS) to bilateral bronchial stenosis due to invasion of lung cancer. A 75-year-old man was admitted to our hospital because of dyspnea and a fainting fit on October 19, 1991. He had been suffered from squamous cell carcinoma of right lung with bilateral bronchial invasion (T4N2M0), which has no indication for surgery. As the stenosis of bilateral main bronchus and the respiratory distress progressed, we applied EMS to the patient and inserted it into the left main bronchus on December 19, 1991. The procedure promptly relieved the respiratory distress and improved his quality of life. Bronchial endoscopy, performed on the 20th postoperative day, revealed the left bronchus patency. Thus, EMS applied to the bronchial stenosis caused by advanced lung cancer may be a choice of palliative therapy and can improve the quality of patient's life. PMID- 8515176 TI - [A case report of Konno's operation for discrete type subaortic stenosis associated with previous VSD closure and repair of coarctation]. AB - A patient, 1 year and 3 month old boy, underwent Konno's operation for severe discrete type subaortic stenosis, which had developed after the coarctation repair (Subclavian Flap Method) at 15 day old and VSD closure at 21 day old. Konno's operation was performed successfully with SJM 21A and postoperative course was uneventful. The discrete type subaortic stenosis may also develop after VSD closure complicating with coarctation complex. Konno's operation is an acceptable method and stenotic left ventricular outflow tract can be enlarged sufficiently in even young infants. This is the youngest patient treated successfully with Konno's operation in Japan. PMID- 8515177 TI - [Surgical treatment of membranous ventricular septal aneurysm with posterior ventricular septal defect--a case report]. AB - A 45-year-old woman was hospitalized for examination of a cardiac murmur. She had undergone surgery for a membranous ventricular septal defect at the age of 22. Cardiac catheterization showed a membranous ventricular septal aneurysm and a residual shunt. At reoperation, we found the membranous septal aneurysm to be accompanied with a posterior ventricular septal defect. The septal defect was closed with a Dacron patch, and the septal aneurysm was excised, with direct closure. Membranous ventricular septal aneurysm is generally associated with membranous ventricular septal defect. Cases of membranous ventricular septal aneurysm with posterior ventricular septal defect are rare. PMID- 8515178 TI - [Non-enzymatic lysins: action mechanism of molluscan vitelline coat lysis]. PMID- 8515179 TI - [Asparaginylendopeptidase: an enzyme probably responsible to post-translational proteolysis and transpeptidation of proconcanavalin A]. PMID- 8515180 TI - [Sarafotoxin]. PMID- 8515181 TI - Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients. AB - Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. Analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p < 0.004). Patients carrying the DR2 alleles, DRB1*1501, *1502 or *1601 were at a lower risk of producing anti-donor HLA antibodies. PMID- 8515182 TI - CD45 expression by murine B cells and T cells: alteration of CD45 isoforms in subpopulations of activated B cells. AB - The CD45 family of high molecular weight cell surface glycoproteins is abundantly expressed by virtually all hematopoietic cells. CD45 molecules exist as multiple isoforms whose extracellular portions vary in protein structure and carbohydrate content but whose intracellular portions are highly conserved and possess tyrosine phosphatase activity. In this review we summarize current studies describing CD45 isoform expression on peripheral and thymic lymphocytes. Further, we analyze changes in CD45 isoform expression by selective populations of activated B cells. PMID- 8515185 TI - Minimum standards for the description of participants in learning disabilities research. CLD Research Committee. PMID- 8515186 TI - Arithmetic disabilities, specific and otherwise: a neuropsychological perspective. AB - From a neuropsychological perspective, this article summarizes research that addresses some of the developmental interactions of disabilities in reading, spelling, and mechanical arithmetic. The focus is on two subtypes of children with learning disabilities who exhibit equally impaired levels of arithmetic achievement, but with vastly different patterns of neuropsychological assets and deficits. Qualitative as well as quantitative analyses lead to the conclusion that one of these patterns of neuropsychological assets and deficits (i.e., the nonverbal learning disabilities syndrome; NLD) leads--at the same time and in much the same manner--to specific patterns of impairment in mechanical arithmetic and in psychosocial functioning. The other pattern (Group R-S) is found to lead to particular patterns of academic deficits (including arithmetic), but not to any particular level or type of psychosocial dysfunction. The manifestations of the NLD profile in various types of neurological disease, disorder, and dysfunction are also explored. PMID- 8515187 TI - Early reading performance: a comparison of teacher-based and test-based assessments. AB - An unresolved question in early screening is whether test-based or teacher-based assessments should form the basis of the classification of children at risk of educational failure. Available structured teacher rating scales are lacking in predictive validity, and teacher predictions of students likely to experience reading difficulties have yielded disappointing true positive rates, with teachers failing to identify the majority of severely disabled readers. For this study, three educational screening instruments were developed: (a) a single teacher rating, categorizing children into three levels of reading ability (advanced, average, poor); (b) a 15-item teacher questionnaire designed to measure students' cognitive and language ability, attentional and behavioral characteristics, and academic performance; and (c) a battery of language and reading tests that are predictive of, or correlate with, reading failure. The concurrent validity of each instrument was assessed in a sample of 312 Australian schoolchildren from kindergarten, Year 1, and Year 2. Students were assessed at the end of the 1989 school year after having completed 1, 2, or 3 years of schooling. The results suggest that the nature of the skills required for success in reading changes in the first 3 years of schooling. Both teachers and tests concur more closely as children progress through the elementary years and as the risk behavior (reading) becomes more accessible to direct measurement. Carefully focused teacher rating scales may be a cost-effective means of identifying children at risk of reading failure. Improved teacher rating scales should be developed and used to assist in the early screening process. PMID- 8515183 TI - A hypothesis resolving the apparently disparate activities of native and altered forms of human C-reactive protein. AB - Although C-reactive protein (CRP) has been studied for over 60 years, the in vivo function of this acute-phase reactant has not been clearly defined. The literature on CRP has been divided here into three categories: the cyclic, pentameric blood-borne form of CRP termed 'native' CRP which has activities mainly associated with the resolution of inflammation, conformationally altered and aggregated forms of CRP which display pro-inflammatory properties, and proteolytic forms of CRP exhibiting mixed activities. Since the activities of certain forms of CRP in some cases contradict others, a hypothesis has been developed which reconciles these differences. It is proposed that distinct species of CRP are formed which have unique activities at an inflammatory site; conformationally altered and proteolytic forms of CRP are created in succession from bound native CRP at the inflammatory site due to local conditions (e.g. lowered pH, oxygen radicals, or possibly enzymes). Aggregated and/or conformationally altered forms of CRP initially promote inflammation, and subsequently produced peptide products either up or down regulate different leukocyte activities to aid in the progression of the inflammatory event. As the local conditions favoring the conversion of native CRP to altered forms begin to subside, native CRP then predominates at the site, facilitating the removal of cellular debris and resolution of the lesion. PMID- 8515188 TI - Knowledge of writing and the composing process, attitude toward writing, and self efficacy for students with and without learning disabilities. AB - Twenty-nine seventh- and eighth-grade (21 males and 8 females) and 10 fourth- and fifth-grade (7 males and 3 females) students with learning disabilities, as well as 18 seventh- and eighth-grade (14 males and 4 females) and 11 fourth- and fifth grade (7 males and 4 females) normally achieving students, were administered an interview designed to assess their knowledge of writing and the composing process, attitude toward writing, and self-efficacy as a writer. Students with learning disabilities were found to have less mature conceptualizations of writing than their normally achieving counterparts. Furthermore, while students with learning disabilities were generally positive about writing, they viewed it less favorably than their regular classmates. Finally, there were no differences between the two groups of students in their evaluations of their competence in either writing or carrying out the processes underlying effective composing. PMID- 8515184 TI - Current concepts in DRA gene regulation. AB - The purpose of this review is to provide an interpretative view of work from our laboratory on the DRA gene, and incorporate it with work from other laboratories. Specially, we will deal with: (a) the functional roles of transcription factors in DRA gene regulation; (b) the mechanisms of DRA induction by cytokines; (c) the analysis of DRA gene control in primary untransformed cells, and (d) interactions among transcription factors critical for DRA gene expression. PMID- 8515189 TI - The effects of tape-recorded self-instruction cues on the mathematics performance of students with learning disabilities. AB - The effects of tape-recorded self-instruction cues on the mathematics performance of students with learning disabilities (LD) were investigated. Nine students were assigned to one of three conditions: an experimental condition, in which students attended two training sessions in self-instruction (SIT); an observer condition, wherein students observed SIT but did not participate; and a control condition, wherein students received neither training nor the opportunity to observe. Using a multiple probe design, data (problems attempted, problems completed correctly, and time for task performance) were collected across two baseline phases, two brief instructional periods, and two generalization phases. Without access to taped cues, experimental and observer students did not successfully utilize the SIT after the first self-instructional training. However, when experimental students were trained to use taped cues, they demonstrated the ability to accurately solve their problems. More important, they were able to successfully use SIT procedures when the taped cues were faded. PMID- 8515190 TI - Phoneme awareness and future reading ability. AB - This study investigates two group-administered tests of phoneme awareness, a phoneme segmentation test and an invented spelling test. Each was given to 100 kindergarten children (48 female, 52 male), along with two tests of visual-motor ability. One year later the same children received standardized reading tests and portions of an IQ test. Scores on each test of phoneme awareness predicted between 30% and 40% of variance in first-grade reading ability. In contrast, scores on the tests of visual-motor ability bore a less systematic, less substantial relation to future reading ability. PMID- 8515191 TI - Comparing two modes of teaching a question-answering strategy for enhancing reading comprehension: didactic and self-instructional training. AB - This study investigated the comparative efficacy of two instructional approaches- didactic teaching and self-instructional training--in teaching average and poor readers a comprehension question-answering strategy. Forty-five average students and 45 poor readers from Grades 5 and 6 participated. These 38 girls and 52 boys were equally and randomly assigned to one of three treatment conditions: didactic teaching of the strategy, self-instruction, or control (no training). Students in the first two treatment conditions learned a mnemonic strategy ("Here," "Hidden," and "in my Head") to indicate question-answer relationships that are text explicit, text implicit, or script implicit, respectively. Essentially, the 3H mnemonic cued students to use appropriate text and/or knowledge-base information in answering comprehension test questions. In addition, students in the self instruction group learned three self-questions to guide their use of the 3H strategy. Specifically, the self-questions focused students' attention on the task, provided a basis for decision making concerning the categorization of comprehension test questions, and reminded students to check their answers. The results indicated that both didactic teaching and self-instructional training of the strategy effected significant improvements in students' reading comprehension performance. However, self-instructional training was more effective in enhancing and maintaining students' reading comprehension performance than didactic teaching. Moreover, results from the oral questionnaire indicated that the 3H strategy training increased students' general meta-cognitive knowledge. Lastly, of the 60 trained students, 52 wrote that they would encourage other children to learn the 3H strategy. Thus, the response to strategy learning was clearly positive. PMID- 8515192 TI - On the liability crisis and the glut of litigators. PMID- 8515193 TI - Health care reform: a view from the left. PMID- 8515194 TI - Health care reform: a view from the right. PMID- 8515195 TI - Too many lawsuits. PMID- 8515196 TI - Global budgets--the golden rule. PMID- 8515197 TI - Sound collection strategy: how to get what is rightfully yours. PMID- 8515198 TI - Limited liability companies--the physician joint venture of the future? PMID- 8515199 TI - Current status of epilepsy surgery. AB - In the United States, there are approximately 75,000 patients with medically intractable epilepsy of focal origin who are candidates for ablative surgery. Currently, about 1500 epilepsy operations are performed per year in the United States. Candidates for ablative surgery (i.e., removal of epileptogenic tissue) are those with a reasonable chance of reduction in seizure frequency and improvement of overall lifestyle. The epileptogenic tissue must be localized preoperatively by either non-invasive or invasive recordings, or by imaging studies (e.g., MRI). Nearly 60% of all patients who undergo resection of a temporal or extra-temporal seizure focus become seizure free, and about 70% have no seizures or only rare ones. The most commonly performed operation is anterior temporal lobectomy. This update article will also review the results of other epilepsy operations which are currently performed--hemispherectomy, corpus callosotomy, and multiple subpial transection. PMID- 8515200 TI - Medicine in the 21st century. PMID- 8515201 TI - Primary hyperparathyroidism secondary to parathyroid carcinoma: report of a case. AB - Distinguishing parathyroid carcinoma from benign hyperparathyroidism is often difficult. Clinical features most commonly associated with parathyroid carcinoma, such as palpable cervical mass, markedly higher serum calcium, high parathyroid hormone immunoassay, and evidence of bone disease may not be present. Therefore, intraoperative recognition is essential. We report a case in which the presenting symptoms, physical examination, and laboratory analysis were consistent with benign disease. During surgery, the finding of an enlarged firm gland with surrounding inflammatory reaction altered the approach to include the possibility of parathyroid carcinoma. The gland and surrounding tissue were removed, and pathologic examination led to the diagnosis of carcinoma. At 18-month follow-up, the patient was free from recurrence. Any parathyroid gland with a gray appearance, firm texture, and surrounding inflammatory reaction should be treated as carcinoma. Initial intraoperative recognition offers the best chance for cure, since local recurrences are rarely curable. PMID- 8515202 TI - Effects of an antiandrogen treatment on the antler cycle of male fallow deer (Dama dama L.). AB - Weekly application of the antiandrogen cyproteron acetate (CA) to 3 adult (group 1, treatment starting 3 weeks prior to the rut) and 4 subadult (group 2, treatment starting after the rut) fallow bucks led to premature antler casting after about 9 weeks (group 1) or 16 to 17 days (group 2). Variation in time span between onset of CA administration and induced casting (in late November/early December) is attributed to age- and season-dependent differences in androgen levels before and during the treatment period. Casting surfaces of the antlers were flat. In all bucks, casting was followed by a complete though shortened antler cycle, occurring under short day conditions. In February/March velvet was shed from the antlers, indicating a rise in plasma androgen levels at that time. At time of fraying, antlers exhibited signs of immaturity and were shorter than normal. In the most pronounced case of immaturity, the antlers consisted mainly of cancellous woven bone, revealing that bone remodeling and antler mineralization had not occurred to a larger extent. These observations prove that onset of fraying behaviour does not depend on prior maturation of antler bone or necrosis of velvet. Occurrence of the additional antler cycle in late autumn and winter had no negative effect on subsequent antler formation starting in the following spring. PMID- 8515203 TI - Interactions of temperature and steroids on larval growth, development, and metamorphosis in a toad (Bufo boreas). AB - The effects of temperature and steroids [testosterone (T), estradiol (E2), and corticosterone (B)] on premetamorphic growth and development were investigated in the toad (Bufo boreas). The effects of steroids were both temperature and age dependent. In the first experiment, steroids (1.1-1.4 microM) were administered by dissolving them in the water beginning 1 day after hatching at 22 degrees C or 27 degrees C. At 22 degrees C, B inhibited growth (P < 0.001) but had no significant effect on development. Forelegs never emerged in B-treated animals and all died before complete tail resorption. Discontinuation of B treatment allowed normal growth and metamorphosis, but the resulting post-metamorphic animals were significantly shorter (snout-vent length, P < 0.001) than after other treatments. At 22 degrees C, T and E2 had no effect on larval growth and development or size at metamorphosis (P > 0.05), but T induced early foreleg emergence (FLE) (P < 0.005). At 27 degrees C, B was fatal after 2 weeks of treatment, and T and E2 inhibited growth (P < 0.001) and development (P < 0.001), but did not affect time to FLE. In a second experiment at 27 degrees C, treatment with 1.1 microM B starting 15 days after hatching induced early metamorphic events (P < 0.001), such as tail resorption and emergence of the left foreleg (but not the right), but jaw and head restructuring failed to occur. All B treated animals died before complete tail resorption. In a third experiment, 0.275 and 1.11 microM B, starting at day 43 (stage 43), induced early FLE (P < 0.05) and decreased snout-vent length at tail resorption (P < 0.005) without a dose effect. A higher dose of B (4.44 microM) decreased snout-vent length at tail resorption and time to FLE (P < 0.05) but did not affect body weight at metamorphosis (P > 0.05). Animals in this experiment survived to complete tail resorption and transformed normally. The actions of B in these experiments closely resemble those observed with administration of thyroid hormones, suggesting that steroids may interact with endogenous thyroid hormones. PMID- 8515204 TI - Development of the ectopically transplanted primordium of epithelial hypophysis (anterior neural ridge) in Bufo japonicus embryos. AB - It has recently been demonstrated that the epithelial pituitary of the toad is not stomodeal, but placodal, in origin. The placodal cells in the anterior part of the neural ridge (ANR) of the open neurulae are the exclusive source of the epithelial pituitary gland. The present study was undertaken to see the self differentiating ability of these cells in an ectopic environment. Bufo japonicus embryos at the tailbud stage received implants of either the ANR from open neurula-stage embryos, or the pituitary primordium from tailbud-stage embryos (the ANR derivative beneath the forebrain floor) into the tail. Development of the pars intermedia and the pars distalis was monitored immunohistochemically using antisera against both synthetic alpha melanophore-stimulating hormone (alpha MSH) and bullfrog prolactin (PRL). Neither the immunoreactive alpha MSH cells nor the immunoreactive PRL cells differentiated from the neural ridge when it was dislocated from the original site at the open neurula stage. On the other hand, in grafts of the pituitary primordium transplanted from the tailbud-stage embryos, immunoreactive PRL cells developed invariably and immunoreactive alpha MSH cells were detected at an incidence of 72%. The significance of the role of brain tissue surrounding the pituitary anlage in differentiation of the pars intermedia and pars distalis is discussed. PMID- 8515205 TI - Targeted single-cell induction of gene products in Caenorhabditis elegans: a new tool for developmental studies. AB - Heat shock promoters have been employed to achieve tightly regulated expression of transformed genes in a wide variety of model systems including tissue culture cells, bacteria, yeast, Drosophila, and more recently Caenorhabditis elegans. Here we investigate the feasibility of using a laser microbeam to induce a sub lethal heat shock response in individual cells of C. elegans. We demonstrate that in transgenic strains carrying heat shock promoter-lacZ fusions, single cell expression of beta-galactosidase in a variety of cell types of endodermal, mesodermal, or ectodermal origin can be achieved after pulsing with a laser. A tissue-general, inducible promoter can therefore be converted into one of single cell specificity which can be induced rapidly at any point in development, offering unique opportunities to study cell-cell interactions in C. elegans. This technique defines a new approach to generate mosaic animals and may be adaptable to other organisms or tissues. PMID- 8515206 TI - Probing the functions of endogenous lectins: effects of a monoclonal antibody against the neural crest-stage lectin of Xenopus laevis on trunk development. AB - Trunk neural crest of Xenopus laevis has been confronted prior to migration with whole or fragments of a monoclonal antibody raised against the carbohydrate binding site of the endogenous neural crest-stage galactoside binding lectin (Milos et al.: Anat. Embryol., 182:319-327 '90). External fin formation was inhibited in confronted regions but extensive internal matrix develops suggesting interiorization of fin tissue. In the regions of missing fin, the myotomes overgrew the neural tube and dorsal root ganglion neuronal numbers became more variable. Melanophore numbers in regions of missing fin did not change but a significantly greater proportion of the pigment cells localized on the muscle surface that had overgrown the neural tube suggesting that the pigment cell population redistributed itself to occupy a greater myotomal area. PMID- 8515207 TI - A discussion of creatinine analysis in single collection urine specimens. PMID- 8515208 TI - Mitochondrial DNA sequence analysis of human skeletal remains: identification of remains from the Vietnam War. AB - Deoxyribonucleic acid (DNA) sequence analysis of the control region of the mitochondrial DNA (mtDNA) genome was used to identify human skeletal remains returned to the United States government by the Vietnamese government in 1984. The postmortem interval was thought to be 24 years at the time of testing, and the remains presumed to be an American service member. DNA typing methods using nuclear genomic DNA, HLA-DQ alpha and the variable number of tandem repeat (VNTR) locus D1S80, were unsuccessful using the polymerase chain reaction (PCR). Amplification of a portion of the mtDNA control region was performed, and the resulting PCR product subjected to DNA sequence analysis. The DNA sequence generated from the skeletal remains was identical to the maternal reference sequence, as well as the sequence generated from two siblings (sisters). The sequence was unique when compared to more than 650 DNA sequences found both in the literature and provided by personal communications. The individual sequence polymorphisms were present in only 23 of the more than 1300 nucleotide positions analyzed. These results support the observation that in cases where conventional DNA typing is unavailable, mtDNA sequencing can be used for human remains identification. PMID- 8515209 TI - Genetic typing of HLA class II genes in Swedish populations: application to forensic analysis. AB - In an attempt to determine the value of DNA based typing of HLA class II loci to forensic analysis, allele and genotype frequencies at DQA1, DQB1, DPB1, and DRB1 were determined in samples from two Swedish populations using hybridization with sequence specific oligonucleotides to PCR amplified DNA. Significant allele frequency differences were observed at the DQB1 and DRB1 loci between the two populations, as well as between one of the Swedish and a Norwegian population. The average heterozygosity varies between 0.74 to 0.91 and the power of discrimination between 0.90 to 0.98, with the highest values obtained for the DRB1 locus. The probability of genotype identity by chance differs on average 2% between the populations. When applied to a paternity case with one parent deceased and a criminal case, typing of class II loci proved in both cases informative. Analyses of DR and DQ genes does not increase the power of discrimination, due to strong linkage, but offers through the reconstruction of putative haplotypes an internal control for the consistency of the typing results at several loci. Typing of the DRB1 and DPB1 loci was found to result in an approximate combined average probability of genotype identity by chance of one in a thousand. PMID- 8515210 TI - Effects of human decomposition on bullet striations. AB - Five different types of bullets, representing the major materials used in centerfire handgun and rifle ammunition, were inserted into the cranial, chest and abdominal cavities, muscle and adipose tissues of a fresh cadaver. The bullets were retrieved after the body was 90% decomposed. Observation and comparison of before and after photographs let each bullet serve as its own control. Results indicate the reactivity of bullet materials and the body region are significant factors affecting the corrosion process and may obscure rifling striations. PMID- 8515211 TI - Acute benzene poisoning: a report of three fatalities. AB - The toxicity of benzene is well established, particularly its chronic effects on the hematopoietic system and its role as a carcinogen. Acute effects are known but less well documented. This case report describes three cases of acute benzene poisoning resulting from an industrial accident aboard a chemical cargo ship. Complete autopsies were performed on all three victims, who showed evidence of cutaneous, respiratory and cerebral injury. In addition, body fluids, brain, body fat, liver and lung were analyzed for benzene, levels of which were consistent with the lipid soluble nature of benzene, although body fat showed better correlation with blood levels than brain, liver or bile. PMID- 8515212 TI - Critical evaluation of postmortem changes in human autopsy cisternal fluid. Enzymes, electrolytes, acid-base balance, glucose and glycolysis, free amino acids and ammonia. Correlation to total brain ischemia. AB - By studying early postmortem changes in cerebrospinal fluid (CSF) it is possible to draw conclusions as to premortem focal brain cell injury and terminal brain ischemia. Cisternal fluid (CF) from 40 different adult cadavers with no known neurological disorder was analyzed and compared with known in vivo values. They were divided into four groups (n = 10 in each group), CF samples taken 2, 4, 10, and 24 h after death. The enzyme activity of CK and CK-BB (EC 2.7.3.2) increased linearly and statistically significantly 4-24 h postmortem (P < 0.001) the 2 h values being already 10 to 20 times higher than in vivo, LD and its isoenzymes 1 to 3 (EC 1.1.1.27) distinctly 10 to 24 h after death. Glucose and pyruvate concentrations in the CF declined, as did Na+ and Cl-. Lactate and K+ increased over time. The earliest statistically significant changes between different timepoints were seen in lactate, pyruvate and K+ concentrations. The GABA concentration was already more than 170 times at 2 h postmortem, and glutamate more than 20 times higher than in vivo. The concentrations of alanine, glycine, lysine, histidine, isoleucine, phenylalanine, and tyrosine were 2 to 3 times higher at 2 h postmortem than during life. The concentrations of all amino acids and ammonia increased linearly and statistically significantly (P < 0.001) in the CF 4 to 24 h postmortem. PMID- 8515213 TI - Isolated myocardial fibrosis as a cause of sudden cardiac death and its possible relation to myocarditis. AB - In performing medicolegal autopsies on sudden deaths, there occur a number of cases in which no cause of death can be found. In particular, no evidence of macroscopic cardiac abnormalities can be observed. However, extensive histological screening may reveal isolated areas of myocardial fibrosis. The five cases presented discuss the etiology of this fibrosis and its possible relation to myocarditis. The cases involve white women between the ages of 19 and 25 with no previous medical history. The weight of the heart in all five cases was normal. Macroscopic evidence of fibrosis was visible in four out of five cases. No other macroscopic abnormalities were observed. Histologically, there was evidence of scarring or interstitial fibrosis in all five cases. In four of the cases, additional screening permitted the observation of dispersed inflammatory foci consisting of lymphocytes, plasmocytes and macrophages. Two of the cases demonstrated eosinophil and neutrophil aggregates in the center of necrotic foci. No evidence of vascular inflammatory phenomena was observed in any of the five cases. According to the Dallas criteria, three of the five cases fulfill the requirements for myocarditis and one of the five cases for borderline myocarditis. The Dallas criteria, however, do not take into consideration the possible association between inflammation and myocardial fibrosis since many of the reported series of myocarditis have been from hospital autopsies or endomyocardial biopsies and have not taken into account sudden death from fibrotic sequelae of myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515214 TI - Aspartic acid racemization in intervertebral discs as an aid to postmortem estimation of age at death. AB - We investigated whether measurement of aspartic acid racemization in intervertebral discs (IVD) could be used in the postmortem estimation of age at death. The extent of aspartic acid racemization in IVD tissues was found to increase with age. The rate of racemization turned out to be much higher in the nucleus pulposus than in the annulus fibrosus. The relation between age and the D aspartic acid content in the anterior peripheral annulus fibrosus of IVD was close enough to allow postmortem estimation of age at death based on the extent of aspartic acid racemization in this tissue. PMID- 8515215 TI - Opiate concentrations in human head, axillary, and pubic hair. AB - The concentrations of morphine and codeine were investigated in hair from the head, axillary and pubic regions obtained from 12 fatal heroin cases. Hair preparation involves a decontamination procedure in dichloromethane at 37 degrees C for 15 min, solubilization in sodium hydroxyde at 100 degrees C for 5 min, neutralization with hydrochloric acid and centrifugation. After extraction in chloroform-isopropanol-n-heptane (50:17:33; v/v) at pH 9.2, drugs were derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column. Quantification was done by GC/MS using selected ion monitoring. The highest morphine concentrations were found in pubic hair (0.80 to 41.34 ng/mg), followed by hair of the head (0.62 to 27.10 ng/mg), and axillary hair (0.40 to 24.20 ng/mg). Codeine was also detected in all samples, and the codeine-to-morphine ratios ranged from 0.069 to 0.273. The differences observed in drug concentration in the 3 types of hair are discussed in the light of the existing literature. PMID- 8515216 TI - Interpretation of low postmortem concentrations of ethanol. AB - The interpretation of postmortem blood ethanol concentrations (BAC), especially those less than 0.05 g/dL can be complicated by postmortem ethanol formation. One method used by the toxicologist to respond to this possibility is to analyze multiple specimens for ethanol. Two useful specimens to analyze are vitreous humor and urine, because they are less susceptible to the putrefaction process. A negative vitreous humor and/or urine ethanol would suggest that the measured ethanol resulted from postmortem formation. Data were collected from the Office of the Chief Medical Examiner, State of Maryland and the Armed Forces Institute of Pathology on blood specimens with ethanol concentrations less than 0.05 g/dL to develop a reasonable threshold for interpretation in the absence of other specimens. A total of 381 cases with a BAC between 0.01 and 0.04 g/dL were studied over a 2 year period. Urine and vitreous humor specimens were tested where available. At a BAC of 0.01 g/dL, 54% of the cases were associated with a positive vitreous humor and/or urine ethanol concentration. This percentage increased to 63% when BAC equals 0.02 g/dL. Seventy-three percent and 92% of the cases had a positive alternate specimen if the BAC was 0.03 g/dL and 0.04 g/dL, respectively. In addition, 90% of the cases where both vitreous humor and urine were analyzed showed consistent results, that is both specimens were positive or negative. This suggests that in the absence of additional information, a BAC of 0.04 g/dL or higher probably resulted from ethanol consumption. PMID- 8515217 TI - Solid phase extraction of morphine from whole blood by means of Bond Elut Certify columns. AB - The use of Bond Elut Certify columns for the isolation of morphine from whole blood was evaluated. In order to monitor possible losses and the elution profile of morphine, a small amount of the tritiated analogue was added to the samples. Four sample pretreatment methods, three protein precipitation methods and one sonication/dilution method, were tested. The latter one gave the best results. The blood sample was applied onto the column at pH 3.3 after sonication and dilution with 0.1 M phosphate buffer (pH 3.3). The retention of morphine was affected by the pH of the samples, and the loss of morphine during sample application was minimized at low pH (3.3). The interferences were removed by washing the column with the phosphate buffer, 0.01 M acetic acid (pH 3.3), and methanol, sequentially. Ammoniated methanol, 2 mL at 2%, was selected to elute morphine. As a result, more than 80% of 3H-morphine was recovered for concentrations of morphine ranging from 5 to 4000 ng/mL. PMID- 8515218 TI - Evaluation of morphological and histological adult skeletal age-at-death estimation techniques using ribs. AB - Adult age-at-death estimation standards were applied to an independent sample (N = 50, 55) of documented ages 17.5 to 95 years. Estimates derived from the sternal rib end morphological and from the cortical rib histological techniques were compared with each other and to the documented ages. Comparisons to the documented ages reveal no statistically significant differences between the techniques. However, the comparison of each individual's estimates show a poor correlation (r = 0.54) despite the equal performance of the age estimations on the entire sample. Averaging of the two rib age estimates results in an estimate with a stronger Pearson's r (0.86) and a lower standard error of the estimate (7.5 years). PMID- 8515219 TI - DNA fingerprinting from tissues after variable postmortem periods. AB - DNA typing is a useful tool in forensic cases for determining the identity of remains of humans who have been dead for various periods of time. DNA fingerprinting can be achieved only if high molecular weight DNA (HMWDNA) is extracted from the tissue samples of the bodies even after a long postmortem delay. Analyses were performed on various tissues collected during forensic autopsies of 24 bodies known postmortem ages. Tissues such as blood and kidney were found to be unsuitable for DNA fingerprinting because of a rapid degradation of the DNA after a period of one week. HMWDNA could be successfully extracted from brain cortex regardless of postmortem age. PMID- 8515220 TI - Purification of forensic specimens for the polymerase chain reaction (PCR) analysis. AB - Purification methods of deoxyribonucleic acid (DNA) from degraded and contaminated forensic samples were investigated for polymerase chain reaction (PCR) analysis. DNA extracted from putrefied tissue or bloodstains sometimes contained the copurified contaminant, that was identified as the porphyrin compound (hematin). When contaminated but less degraded DNA was analyzed by PCR, it was necessary to eliminate the impurity by anion exchange column chromatography or chelating resin preparation, and ultrafiltration using Centricon microconcentrators. When highly degraded DNA was analyzed, trace amounts of high molecular weight DNA was recovered by electroelution method, and then further purified by both column chromatography and ultrafiltration. From thus purified samples, the amelogenin gene for sex determination could be amplified by dual PCR technique. PMID- 8515221 TI - The effect of killing and preservative solutions on estimates of maggot age in forensic cases. AB - Length of the oldest maggots recovered from a body often provide an accurate estimate of the time since death. The length of maggots of Protophormia terraenovae (Robineau-Desvoidy) of known age, at peak of feeding, was measured after 5 days immersion in one of 15 killing and preservative solutions, some of which are routinely used at autopsy and in forensic entomology; controls were killed in boiling water. There was shrinkage in all 15 solutions which translated into an underage error of 9.7 h in 70% ethanol, 11 h in San Veino and 16.8 h in formalin. Larvae of Calliphora vicina (Robineau-Desvoidy) underwent even greater shrinkage, which resulted in an underage error of 19.2 h in 70% ethanol, 26.4 h in formalin and 28.8 h in San Veino. Young third instar larvae underwent more shrinkage than older ones, with underage errors (in hours) as follows: P. terraenovae-70% ethanol 24 and San Veino, 24; C. vicina-70% ethanol, 7.2 and San Veino, 14.4. Maggots killed in boiling water and then placed in preservative solutions did not shrink. Length of the crop, which may be useful in age estimates of postfeeding larvae, was not altered significantly for forensic purposes in these solutions. The highly significant alterations in maggot length underscore a need for standardization in the treatment of maggots collected at the crime scene and at autopsy if their length is to be interpreted in a valid and consistent way. Recommendations are made for treatment of maggots wherever they are collected. PMID- 8515222 TI - Confirmation of human identification using computerized tomography (CT). AB - Computerized tomography (CT) was used to assist in confirming a human identification. The potential utility of comparing lateral scout views and lateral skull X-rays for identification purposes is proposed. Antemortem CT scans with scout views of the human skull are useful for comparison with postmortem radiographs and should be considered as a potential modality for establishing definitive identification when antemortem radiographs are not available. PMID- 8515223 TI - Documentation of a doxylamine overdose death: quantitation by standard addition and use of three instrumental techniques. AB - To answer the question, "Is this death due to a drug overdose?" requires at least that the drug be unequivocally identified and a blood concentration reliably determined. The approach taken in this case as standard addition technique and use of three different chromatographic techniques-high performance liquid chromatography (HPLC), high performance thin-layer chromatography (HP-TLC) and gas chromatography/mass spectrometry (GC/MS). Each of the chromatographies was carried out on the same extract by splitting the residue three ways. HPLC provided a quantitative result which was 1.2 mg/L in blood and HP-TLC and GC/MS confirmed this result with additional quantitative data, information about two metabolites (nordoxylamine and dinordoxylamine) and conclusive identification. Blood nordoxylamine was 0.52 mg/L and doxylamine plus metabolites in urine was 25 mg/L. PMID- 8515224 TI - Evaluation of fatal dog bites: the view of the medical examiner and animal behaviorist. AB - The multidisciplinary evaluation of fatal dog bites in the context of a case is discussed. This approach emphasizes detailed examination of the animals including matching of bite marks, autopsy, and canine behavioral analysis. It further provides details such as contributory medical conditions, past animal behavior and physical evidence linking the dogs to the attack. Such information is important in the legal proceedings that usually accompany these events. PMID- 8515225 TI - Cerebral vasculitis associated with cocaine abuse. AB - A variety of central nervous system pathology has been associated with cocaine abuse, including cerebral vasculitis. We report a case of a 25-year-old woman who died of hypoxic encephalopathy following cardiac arrest due to cocaine abuse. Autopsy revealed a distinctive cerebral vasculitis with features characteristic of hypersensitivity drug included vasculitis. The significance of cerebral vasculitis associated with cocaine is reviewed. PMID- 8515226 TI - Identification of gunpowder in healed wounds. AB - A woman received a contact gunshot wound to the abdomen from a .22 caliber revolver. She recovered only to succumb to another gunshot wound six months later. The initial wound was dissected and multiple intact granules of round flake gunpowder were recovered. Cross sections of granules were clearly identifiable in histologic slides. Recovery of intact powder in remote wounds has not been previously described and may help classify the ammunition and weapon used to produce the injury. PMID- 8515227 TI - Analysis of the site for second-strand initiation during replication of the Streptomyces plasmid pIJ101. AB - The indigenous plasmid pIJ101 is the parent of many cloning vectors used in Streptomyces. One early pIJ101 derivative, pIJ702, has been particularly widely used. pIJ702 lacks sti:cop/korB and accumulates single-stranded DNA (ssDNA). The 1.2 kb BclI-BclI sti:cop/korB and 0.7 kb SpeI-BclI sti regions were isolated from pIJ101 and cloned into pIJ702 at the PstI site in both orientations. No ssDNA was detected in constructs containing sti present in its correct orientation with respect to the basic replicon, with or without cop/korB. Constructs which contained sti in the reverse orientation did accumulate ssDNA. Thus, sti is only active as the site for second-strand synthesis in its natural orientation. Furthermore, sti inserted in either orientation into the structurally unstable pIJ702-pUC8 shuttle vectors prevented them from rearranging in S. lividans. The sti function was defined to a 0.53 kb SpeI-SacII fragment and the probable site for second-strand initiation (ssi) was identified. PMID- 8515228 TI - Multiple domain structure in a chitinase gene (chiC) of Streptomyces lividans. AB - One of the chitinases of Streptomyces lividans, chitinase C, was encoded by a 2 kb smaI-XhoI restriction fragment contained in the recombinant plasmid pEMJ7. DNA sequence analysis of this region revealed the presence of two open reading frames (ORF1 and ORF2) which had opposite orientations. Northern analysis showed that only the mRNA complementary to ORF1 was transcribed, and that this transcription was induced by chitin and repressed by glucose. ORF1 showed a codon distribution typical of Streptomyces. A sequence identical to that of the N-terminus of mature secreted chitinase C was found from amino acid residue 31 in the deduced amino acid sequence of ORF1 (619 amino acids), implying that ORF1 encodes a pre-protein of chitinase C. The pre-protein of chitinase C consisted of four discrete domains. The 30 amino acid N-terminal sequence, domain 1, was characteristic of a signal peptide. Domain 2 consisted of 105 N-terminal amino acids of mature chitinase C, and was similar to cellulose-binding domains of several cellulases. Domain 3 (94 amino acids) showed homology with type III homology units of fibronectin. Domain 4, a C-terminal 390 amino acid sequence, is probably the catalytic domain of the chitinase, since it exhibited identity with several other chitinolytic enzymes. PMID- 8515229 TI - Location of the genes for anthranilate synthase in Streptomyces venezuelae ISP5230: genetic mapping after integration of the cloned genes. AB - The anthranilate synthase (trpEG) genes in Streptomyces venezuelae ISP5230 were located by allowing a segregationally unstable plasmid carrying cloned S. venezuelae trpEG DNA and a thiostrepton resistance (tsr) marker to integrate into the chromosome. The integrated tsr was mapped by conjugation and transduction to a location close to tyr-2, between arg-6 and trpA13. A genomic DNA fragment containing trpC from S. venezuelae ISP5230 was cloned by complementation of a trpC mutation in Streptomyces lividans. Evidence from restriction enzyme analysis of the cloned DNA fragments, from Southern hybridization using the cloned trp DNA as probes, and from cotransduction frequencies, placed trpEG at a distance of 12 45 kb from the trpCBA cluster. The overall arrangement of tryptophan biosynthesis genes in the S. venezuelae chromosome differs from that in other bacteria examined so far. PMID- 8515230 TI - Recombination at the coagulase locus in Staphylococcus aureus: plasmid integration and amplification. AB - The integrating plasmid pCOA18, comprising pUC18 linked to a mutated coagulase (coa) gene from Staphylococcus aureus, and constructed by substituting coa sequences with a tetracycline (Tc)-resistance marker (delta coa::Tcr), was transformed into Staphylococcus aureus RN4220, where it underwent recombination with the chromosomal coa locus. Allele-replacement mutants were recovered at a low frequency directly after transformation. The majority of transformants carried pCOA18 integrated in the chromosome by a single Campbell-type recombination event. The majority of integrants contained tandem repeats of pCOA18 and expressed high levels of resistance to Tc (> 30 micrograms ml-1) compared to the single-copy integrants and allele-replacement mutants (15 micrograms ml-1). Transduction of a single-copy integrant to a Coa+ recipient allowed the cointegrant to be resolved and allele-replacement recombinants to be selected. In addition, growth of a single-copy integrant on high concentrations of Tc (> 30 micrograms ml-1) selected for amplified derivatives at a frequency of 10(-5). It was estimated that up to 19 copies of pCOA18 could occur in a tandem array in the chromosome. PMID- 8515231 TI - Characterization of the rnc-97 mutation of RNAaseIII: a glycine to glutamate substitution increases the requirement for magnesium ions. AB - The rnc-97 mutation of the Escherichia coli double-stranded-RNA-specific ribonuclease III (RNAaseIII) was previously isolated by virtue of the lethal expression of RNAaseIII in Saccharomyces cerevisiae. Here we show that rnc-97 is a single point mutation causing the substitution of glycine 97 by glutamic acid. The mutation eliminates the lethal phenotype of RNAaseIII expression in yeast and reduces fourfold the effect of RNAaseIII expression on bacteriophage gy1 propagation in E. coli. Mutant RNAaseIII-G97E and wild-type RNAaseIII were purified according to published procedures. The apparent molecular masses of the two enzymes on SDS polyacrylamide gels are the same but they differ in pI (6.85 for RNAaseIII-G97E and 7.3 for RNAaseIII). Whereas the two enzymes (under standard assay conditions) do not show a great difference in activity towards double-stranded RNA and defined single-stranded RNAaseIII substrates, they differ dramatically (20-fold or more) under conditions of Mg2+ limitation. The hypothesis that limitation of Mg2+ ions in vivo is responsible for the phenotypes of the rnc-97 mutation in S. cerevisiae and E. coli is discussed. PMID- 8515232 TI - Cloning and characterization of a nitrite reductase gene from Alcaligenes faecalis and its expression in Escherichia coli. AB - The gene (nir) encoding the copper-containing nitrite reductase (NIR) of a denitrifying bacterium, Alcaligenes faecalis S-6, was cloned by a synthetic oligonucleotide-probing method. The nucleotide sequence of the cloned DNA fragment revealed the primary structure of the NIR precursor containing the N terminal signal sequence for secretion. A nucleotide sequence, possibly recognized by a transcriptional regulator resembling FNR was found upstream of the structural gene. When the cloned gene was expressed in Escherichia coli under the control of the lac promoter at 37 degrees C, NIR was produced as large inclusion bodies and little activity was detected. When cultivation was at 20 degrees C, most of the NIR was detected in the soluble fraction and a significant portion of the protein was translocated into the periplasmic space, accompanied by removal of its signal sequence. PMID- 8515233 TI - Identification of methanol-regulated promoter sequences from the facultative methylotrophic bacterium Methylobacterium organophilum XX. AB - A promoter-probe vector (pHX200) was constructed using the broad-host-range cosmid pLA2917 and a promoterless xylE gene of Pseudomonas as the reporter gene. Insertion of the cloned promoter fragment of the methanol dehydrogenase large subunit gene moxF (methanol oxidation) in front of the xylE gene in pHX200V-47 resulted in high-level expression of the xylE gene product--catechol 2,3 dioxygenase--in Methylobacterium organophilum XX. The specific activity of the enzyme was four times higher in methanol-grown M. organophilum XX culture than in succinate-grown culture. Interestingly, the insertion of the same fragment in the opposite orientation in front of the xylE gene (pHX200V-74) also led to elevated catechol 2,3-dioxygenase activity. This promoter activity was also methanol regulated. A total of 21 methanol-regulated promoter clones were identified that originate from three gene clusters (groups V, VI and VII) on the M. organophilum XX chromosome involved in methanol oxidation. Vector pHX200 and its derivatives were successfully mobilized into cells of three phylogenetically diverse methylotrophic bacteria: Methylophilus methylotrophus AS1, Methylobacterium extorquens AM1 and Methylobacterium sp. DM4. The reporter gene (xylE) was functionally expressed in all three bacteria with the aid of a proper promoter. Transcriptional fusions of methanol-regulated promoters with the xylE gene were mobilized into Mox- mutants of M. organophilum XX and M. extorquens AM1 to study the roles of methanol oxidation genes, especially regulatory genes. It appeared that vector pHX200 is an efficient promoter probe with wide host-range and an excellent tool for studies of structure and function of promoters/regulators. PMID- 8515234 TI - Sensitivity of elongation factor Tu (EF-Tu) from different bacterial species to the antibiotics efrotomycin, pulvomycin and MDL 62879. AB - The sensitivity of elongation factor Tu (EF-Tu) from different species of bacteria to the EF-Tu-binding antibiotics efrotomycin, pulvomycin and MDL 62879 was tested by measuring the effect of these antibiotics on cell-free protein synthesis systems. EF-Tu from four different Gram-negative species was sensitive to all three antibiotics. Among Gram-positive bacteria, EF-Tu of Bacillus subtilis, Staphylococcus aureus and Enterococcus faecalis was resistant to efrotomycin and less sensitive to pulvomycin than EF-Tu of Gram-negative bacteria. EF-Tus from streptococci were significantly less sensitive than EF-Tus from Gram-negative bacteria to both efrotomycin and pulvomycin. All of the EF-Tus were sensitive to MDL 62879. The same sensitivity pattern emerged from GDP exchange assays, performed with partially purified EF-Tu from different bacterial species and pure Escherichia coli EF-Ts. These results suggest that the site of action of MDL 62879 is more conserved among bacterial species than those of efrotomycin and pulvomycin. Heterogeneity of EF-Tus from different bacterial species was also reflected in differences in their apparent molecular masses estimated by SDS-PAGE. EF-Tus from the Gram-positive species had higher molecular masses than those from all but one of the Gram-negative species. PMID- 8515235 TI - Properties of the cold-labile NAD(+)-specific glutamate dehydrogenase from Bacillus cereus DSM 31. AB - Nicotinamide-adenine-dinucleotide-specific glutamate dehydrogenase (NAD-GDH; EC 1.4.1.3) from Bacillus cereus DSM 31 was enriched 260-fold. The molecular mass was determined by gel filtration to be 270 kDa (+/- 25 kDa). The enzyme was highly specific for the coenzyme NAD(H) and catalysed both the formation and the oxidation of glutamate. Apparent Km values of 7.7 mM for glutamate and 0.56 mM for NAD+ during oxidative deamination were measured. Both in crude cell-free extracts and in enriched preparations the enzyme was extremely unstable, especially at low temperatures. The loss of activity in the cold was found to be due to the dissociation of the holoenzyme into catalytically inactive subunits of molecular mass 48 kDa (+/- 5 kDa), indicating that the native enzyme has a hexameric structure. The activity was restored under certain conditions, and no instability of the enzyme in the cold was observed in undisrupted cells. PMID- 8515236 TI - Characterization of the 6-aminohexanoate-dimer hydrolase from Pseudomonas sp. NK87. AB - The DNA base sequence of the Pseudomonas sp. NK87 gene (P-nylB) for 6 aminohexanoate-dimer hydrolase (P-EII), a xenobiotic-compound-degrading enzyme, was determined. It has an open reading frame of 1188 bp, initiated by ATG and terminated by TAG, and coding for 396 amino acids. The base sequence of the open reading frame has 53% sequence similarity to that of the gene for the same enzyme of Flavobacterium sp. KI72 (F-nylB) and 35% sequence similarity with respect to the deduced amino acid sequence. The P-EII enzyme was purified from an Escherichia coli clone in which the P-EII gene was highly expressed. The P-EII enzyme was inhibited by a serine protease inhibitor, diisopropyl fluorophosphate, as was the F-EII enzyme. Double reciprocal plots obtained from various concentrations of 6-aminohexanoate-dimer indicated that the kcat value of the P EII enzyme (9.2 s-1) was approximately half that of the F-EII enzyme (19 s-1), and the P-EII enzyme had higher affinity toward this substrate (Km for P-EII, 0.6 mM; Km for F-EII, 15 mM). The P-EII enzyme had a temperature optimum of 48 degrees C, and a pH optimum of 7.5. It is speculated that since the P-nylB and F nylB genes are more diverged from each other than the corresponding nylA genes, the latter may have evolved more recently. PMID- 8515237 TI - Diketocamphane enantiomer-specific 'Baeyer-Villiger' monooxygenases from camphor grown Pseudomonas putida ATCC 17453. AB - Pseudomonas putida ATCC 17453 grew with either (+)- or (-)-camphor as sole carbon source. Enantiomer-specific 'biological Baeyer-Villiger' monooxygenases were synthesized irrespective of the camphor isomer used for growth. The two enzymes are probably the products of separate genes but showed many similarities. Each consisted of two electrophoretically identical subunits, bound flavin mononucleotide (FMN) non-covalently and accepted electrons from an induced NADH dehydrogenase which interacted with the FMN bound to the oxygenating component. They showed minor differences in M(r) with 3,6-diketocamphane 1,6-monooxygenase being the smaller enzyme. Isoelectric focussing showed the two enzymes to have different acidic pI values. Polyclonal antibodies raised against 3,6 diketocamphane 1,6-monooxygenase also cross-reacted with 2,5-diketocamphane 1,2 monooxygenase and its subunits. PMID- 8515238 TI - Cyclohexadienyl dehydratase from Pseudomonas aeruginosa is a periplasmic protein. AB - The gene encoding cyclohexadienyl dehydratase from Pseudomonas aeruginosa, designated pheC, was cloned in Escherichia coli and sequenced recently by Zhao et al. (Journal of Biological Chemistry 267, 2487-2493, 1992). N-Terminal sequencing of the purified cyclohexadienyl dehydratase yielded a run of 11 residues which matched perfectly with the deduced amino acid residues 26-36. This showed that a 25 residue peptide was cleaved from the N-terminus of a preprotein formed in E. coli. The amino acid composition of the 25 residue peptide was typical of signal sequences for periplasmic proteins. Most or all of the cyclohexadienyl dehydratase was released from P. aeruginosa and E. coli carrying the pheC gene following spheroplast formation, osmotic shock or chloroform treatment. The location of the enzyme in the periplasm of both E. coli and P. aeruginosa was confirmed by Western blotting analysis using antibody prepared against PheC. Electron microscopy using immunogold labelling showed an apparent localization of cyclohexadienyl dehydratase at the polar regions of the periplasmic space in E. coli. PMID- 8515239 TI - The need for consistent nomenclature and assessment of growth phases in diauxic cultures of Saccharomyces cerevisiae. AB - The need for consistent nomenclature and accurate assessment of late growth phases in diauxic yeast cultures is highlighted by the substantial variation of stress tolerance in Saccharomyces cerevisiae after the exhaustion of the initial fermentable carbon source. At present, a wide variety of assessment methods and confused terminology exists in the literature, leading to difficulties in the interpretation and comparison of published results. A method based on the depletion of ethanol accumulated during the respiro-fermentative growth phase is suggested as suitable for assessing subsequent growth phases and reporting results. Consistent application of nomenclature for growth phases is recommended to assist the interpretation of published experimental results. It is suggested that the phases of growth in diauxic batch culture should be referred to using the terms (1) initial lag phase, (2) respiro-fermentative phase, (3) diauxic lag phase, (4) respiratory phase, (5) stationary phase, and (6) death phase. PMID- 8515240 TI - Ultrastructure of the surface film of bacterial colonies. AB - The structure of the surface of colonies of various Gram-negative and Gram positive bacteria was examined by transmission electron microscopy. The results indicate that bacterial colonies in the course of their development produce a film which becomes thicker with increased duration of growth. The basic part of the film is an elementary membrane, which is a stable structure with a large surface area. The inner and outer surfaces of the film membrane are covered by amorphous layers. These layers are thicker in the surface film of Gram-negative bacterial colonies than in those of Gram-positive bacteria. Membrane vesicles from the bacterial colonies take part in the formation of the surface film. The presence of the film on the surface of the colonies of different bacteria suggests that this structure may play an important role. PMID- 8515241 TI - Protein composition of rhapidosomes isolated from Aquaspirillum itersonii. AB - Rhapidosomes are tubular microstructures composed of proteins that are found in a variety of bacteria and algae. These structures, which are resistant to disruption by many denaturing agents, have potential application as a biomaterial and may serve as a new model for the study of self assembly. When rhapidosomes were purified and analysed by SDS-PAGE the presence of three proteins with molecular masses of 53, 29 and 18 kDa was revealed. However, lysozyme treatment of the rhapidosome preparations containing the three proteins resulted in the selective release of the 18 kDa protein from the rhapidosome complex. N-Terminal sequence analysis and amino acid composition analysis were performed on all three proteins. The amino acid composition of the 18 kDa protein closely matched the amino acid composition of protein H (a peptidoglycan-associated protein from Pseudomonas aeruginosa). These results suggest that the 18 kDa protein may be a contaminating peptidoglycan-associated protein and not part of the rhapidosome structure. Western blot analysis using antisera raised against rhapidosomes revealed that the 53 kDa component protein does not react with the antisera. We speculate that the 53 kDa protein may form the inner core of the rhapidosomes, whilst the 29 kDa protein forms the outer sheath of these structures. PMID- 8515242 TI - Inhibition of the cellulolytic activity of Neocallimastix frontalis by Ruminococcus flavefaciens. AB - A study was made of the antagonistic effect of Ruminococcus flavefaciens on the cellulolytic activity of Neocallimastix frontalis. An extracellular factor inhibiting the cellulolytic activity of the fungus was detected in the bacterial supernatant. The antagonistic factor, which precipitated with ammonium sulphate at 40% saturation, was temperature-sensitive and was destroyed at temperatures above 60 degrees C. After separation by anion-exchange chromatography, sequential precipitation, dialysis and SDS-PAGE, two protein species of 100 and 24 kDa were identified as being involved in this antagonistic effect. It is known whether the proteins are two subunits of a single protein or represent two different proteins. The inhibitory factor, which is not a bacterial cellulase, did not affect fungal growth, but it inhibited the activity of the fungal cellulases. PMID- 8515243 TI - Immunological relatedness of the LamB proteins among members of Enterobacteriaceae. AB - We have studied the immunological relatedness of LamB proteins from a wide range of enterobacterial species, using antibodies directed against denatured Escherichia coli K12 and Klebsiella pneumoniae LamB proteins (LamBE.c. and LamBK.p., respectively), and anti-peptide antibodies directed against 10 distinct loops of LamB from E. coli K12 predicted to protrude either side of the outer membrane. We have shown that a protein immunologically related to LamBE.c. and LamBK.p. was present in all members of Enterobacteriaceae tested. A protein recognized by several anti-peptide antibodies was identified in E. coli, Shigella sonnei, Salmonella typhimurium and Kleb. pneumoniae, as well as in two Citrobacter species, two Enterobacter species and Kluyvera ascorbata. The recognition patterns obtained with the anti-peptide antibodies were in agreement with the LamB protein sequence data available. They indicated that the cell surface and also the periplasmic loops of LamB are subject to great antigenic variability. PMID- 8515244 TI - Comparison of the fatty acid profiles of Borrelia, Serpulina and Leptospira species. AB - Fatty acid methyl ester (FAME) derivatives were examined as a means of characterizing Borrelia burgdorferi isolates and distinguishing them from other spirochaetes. Analysis was performed using a gas liquid chromatography column in conjunction with Microbial Identification System (MIS) software. Reproducible FAME profiles were produced which distinguished Borrelia species, Serpulina hyodysenteriae and Leptospira icterohaemorrhagiae. Furthermore, the FAME profiles of four recognized Borrelia species (including two American isolates of Borrelia burgdorferi, B31 and JD1) were distinct from one another and from the BSK II medium in which they were grown. The results confirm previous reports that FAME profiles of bacteria represent a diagnostic phenotypic property and suggest that they may have applications in the chemotaxonomic classification of Borrelia species. PMID- 8515245 TI - Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization. AB - Titres of antibodies against hepatitis A virus (HAV) were determined in patients, in donors, and in volunteers after active, passive, and combined immunization. Highest titres were found in recently infected persons: in 109 IgM anti-HAV positive persons, the geometric mean titre (GMT) was 15,400 mIU/ml. The GMT in 265 anti-HAV positive blood donors was 10,700 mIU/ml. The anti-HAV seroprevalence in 19,746 donors increases with age: at the age of 40 years, 50% have antibodies. Titres after active, passive, and combined immunization were studied in three groups: 51 persons received inactivated HAV vaccine at months 0, 1, and 6. The GMT after the booster was 3,400 mIU/ml at month 7. All persons produced more than 100 mIU/ml anti-HAV. Forty-nine persons received both 5 ml immunoglobulin and three vaccinations, yielding a GMT of 1,300 mIU/ml at month 7. One person in this group produced less than 100 mIU/ml anti-HAV. Forty-nine persons received 5 ml immunoglobulin intramuscularly. At day 5 the GMT was 96 mIU/ml. The estimated minimum protective level (10 mIU/ml) was reached in 3 months. Hepatitis A vaccination may supersede the use of immunoglobulin as prophylaxis for travellers to endemic areas. Passive immunization remains necessary for protection during outbreaks. The dosage regimen for passive immunization is based on old studies using preparations with unknown anti-HAV content. Concern regarding the antibody levels in immunoglobulin preparations is justified; the prevalence of HAV antibodies in developed countries continues to fall. Our results indicate that dosage regimens should be reconsidered. Dosage should be deduced logically from the anti-HAV antibody content of the immunoglobulin preparation. PMID- 8515246 TI - Infection of epithelial cell line HEp-2 with human immunodeficiency virus type 1 is CD4 dependent. AB - HEp-2 cells, human epithelial cells derived from a larynx carcinoma, were found to be highly susceptible to infection with HIV-1 stain IIIb and MN, but not to infection with the monotropic strain IIIBa-L or the clinical isolate HIV-1AT. HEp 2 cells infected with HIV-1 IIIb continuously secreted high levels of p24 antigen, while no cytopathic effects were observed. Although no CD4 antigen could be detected on the cells by flow cytometric analysis, CD4 mRNA was detected by reverse transcriptase PCR. Furthermore, infection could be blocked by anti-CD4 monoclonal antibody OKT4a indicating a CD4 mediated viral entry in HEp-2 cells. HEp-2 cells are commonly used in clinical virology for the culture of different viruses from clinical specimens. HEp-2 cells should therefore be handled with caution as they may potentially become infected with HIV. PMID- 8515247 TI - Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection. AB - The therapeutic potential of plant extracts of Phyllanthus amarus and Phyllanthus maderas patensis for postexposure prophylaxis against infection by Hepadnaviruses was studied in ducklings infected by the duck hepatitis B virus (DHBV). Forty four Pekin ducklings were inoculated intraperitoneally with DHBV at 24 hr post hatch. They were treated by intraperitoneal injection of Phyllanthus amarus (aqueous extract) (100 mg/kg body weight) or Phyllanthus mad eraspatensis (alcoholic extract) (100 mg/kg body weight) for a period of 4 weeks. Infected ducklings treated with saline served as controls. Weekly serum samples obtained before, during, and after treatment were analysed for the presence of DHBV DNA in serum by dot blot hybridisation using alpha 32P-labelled probes. Liver tissue was collected after killing the ducks at various time intervals and was studied for replicative status of the viral DNA and liver histopathology; 17 of 21 ducks were viraemic on completion of treatment with Phyllanthus amarus. At 16 week posttreatment follow-up four of seven animals remained viraemic. Similar results were obtained with Phyllanthus maderaspatensis. There was no alteration in DHBV replication in the liver. No toxicity was observed with this treatment. These observations suggest that Phyllanthus amarus and Phyllanthus maderaspatensis are not useful as therapeutic agents for postexposure prophylaxis against DHBV infection. PMID- 8515248 TI - Clusterin levels increase during neuronal development. AB - The expression of clusterin has been shown to be elevated in several models of experimentally induced programmed cell death and in association with a number of neurodegenerative conditions. In order to test whether this protein is expressed in neurons during development, the expression of clusterin was examined in the developing nervous system, using immunohistochemistry and mRNA analysis. Clusterin expression was observed in the earliest neurons of the cortical plate on embryonic day (E) 12. Thereafter, the intensity of clusterin staining continued to increase in an age-dependent manner, with the greatest intensity of staining being found in the postnatal mature brain. Virtually all neurons were clusterin-positive and there was no evidence for the appearance of clusterin positive cells specifically during epochs of programmed neuronal death in the embryo. This study suggests that clusterin has a role in neuronal maturation and it is unlikely to be associated exclusively with neuronal cell death. PMID- 8515250 TI - Comparison of the physiology of the auditory receptor organs in Gryllus bimaculatus and Ephippiger ephippiger: CSD recordings within the auditory neuropiles. AB - The syllables of the song of the tettigoniid Ephippiger ephippiger consist of a series of short sound impulses with a broad-banded frequency spectrum. Syllables of the song of the gryllid species Gryllus bimaculatus are nearly pure tones with sharply tuned frequency maxima. A comparison of the physiology of the auditory receptor organs of both species was carried out by using acoustical stimuli with different carrier frequencies and time-amplitude patterns. The neuronal ensemble activity of receptor cell groups of the tympanal organ was measured within the prothoracic ganglion using the CSD technique. In E. ephippiger, response maxima were found at carrier frequencies mirroring the broad frequency content of the conspecific song. The receptor cells of E. ephippiger are highly sensitive to transient sound impulses. In G. bimaculatus, the receptor cell population is more sharply tuned to the basic frequencies of the natural songs; pure tones represent more effective stimuli than transient sound signals. The causes for these species specific differences are discussed with regard to probable adaptations of the receptor organs to the parameters of the conspecific songs. PMID- 8515249 TI - Induction of programmed cell death in a dorsal root ganglia X neuroblastoma cell line. AB - Growth factor-dependent neurons die when they are deprived of their specific growth factor. This "programmed" cell death (PCD) requires macromolecular synthesis and is distinct from necrotic cell death. To investigate the mechanisms involved in neuronal PCD, we have studied the sequence of events that occur when a neuronal cell line (F-11: mouse neuroblastoma X rat dorsal root ganglia) is deprived of serum in a manner analogous to growth factor deprivation from neurons. Protein synthesis was inhibited within the first 8 h of serum deprivation, while DNA cleavage into nucleosome ladders was prominent by 24 h. The DNA cleavage could be inhibited by cycloheximide, consistent with a requirement for protein synthesis. In contrast, mitochondrial function was not compromised by serum deprivation. Rather, the cells appeared to be metabolically activated after serum removal as shown by an increased reduction of MTT by mitochondrial dehydrogenases and an increase in cellular autofluorescence, which is thought to be due to elevated levels of NADH and flavoproteins. Assessment of cell viability by propidium iodide staining showed no indication of cell death within 24 h. After 48 h of serum deprivation, cells decreased in size and increased propidium iodide uptake. Thus, serum deprivation activates PCD in F-11 cells and may be a useful model to study the intracellular events responsible for PCD. PMID- 8515251 TI - Formation of functional synapses by regenerating adult rat retinal ganglion cell axons in midbrain target regions in vitro. AB - The ability of adult rat retinal ganglion cell (RGC) axons to reinnervate normal target regions was examined in vitro. In co-culture experiments, adult rat retinal explants were placed adjacent to fetal rat midbrain sections that contained the superior colliculus (SC) which is the main target for RGC axons. Adult rat RGCs regrew axons over more than 500 microns on a polylysine-laminin substrate to reach the co-cultured explants. By using neurofilament immunohistochemistry and the fluorescent dye DiI for anterograde and retrograde tracing, it was shown that (1) adult rat RGCs with a stereotyped morphology survived in explant cultures for more than 4 weeks in the presence of fetal midbrain explants, (2) regenerating RGC axons preferentially terminated within midbrain target regions, and (3) RGCs formed functional synapses. In addition, the maturation of the SC region in midbrain explants was examined histologically and ultrastructurally to demonstrate appropriate target development. PMID- 8515252 TI - Song-selective auditory input to a forebrain vocal control nucleus in the zebra finch. AB - Neurons in nuclei on the motor pathway for vocalizations in songbirds are known to respond to sound stimuli. The auditory responses in one such nucleus, robustus archistriatalis (RA), were characterized by making multi-unit recordings in awake and anesthetized adult male zebra finches and in birds that had received lesions of the input to RA from the lateral part of the magnocellular nucleus of the anterior neostriatum (LMAN) or the Higher Vocal Center (HVC). In awake birds, RA neurons have a high level of spontaneous activity and vigorous auditory responses to song stimuli. Significantly greater responses are seen to the bird's own song (BOS) than to BOS played in reverse (REV) or to the songs of conspecifics (CON). Under ketamine-xylazine anesthesia, spontaneous activity is reduced, response latency increases and responses to BOS, REV and CON are indistinguishable. Responses obtained under urethane anesthesia are similar to those seen in awake birds. Thus, the pattern and selectivity of auditory responses in RA depend on the animal's state. Auditory responses in RA are qualitatively unchanged following lesion of the input to RA from LMAN, indicating that this pathway is not required for the sensory processing that underlies the preference for BOS on the vocal production pathway. Our results show that an input other than that from LMAN must be primarily responsible for auditory responses in RA. The direct projection from HVC is the most likely pathway by which song selective auditory information arrives in RA, since lesioning HVC abolished auditory responses in RA. PMID- 8515253 TI - Calcium regulates neuronal differentiation both directly and via co-cultured myocytes. AB - Control of neuronal development by cellular interactions can be regulated by both extracellular and intracellular calcium. Removal of extracellular calcium affects the differentiation of amphibian spinal neurons in vitro by preventing neuronal calcium influx during the production of calcium-dependent action potentials (Holliday and Spitzer, Dev. Biol. 141:13-23, 1990). However, this culture condition affects differentiation through other mechanisms as well. We have investigated the interaction between neurons and myocytes to distinguish direct effects of low extracellular calcium on neuronal differentiation and indirect effects due to interference with neuron-myocyte interactions. We have examined the initiation of neurite outgrowth and the subsequent extension and orientation of processes. We find that (1) the number of neurons that initiate process outgrowth is reduced by the presence of myocytes in a standard medium containing calcium. Experiments with muscle-conditioned medium indicate that the production and/or secretion of inhibitory cues is calcium dependent. (2) When neurite initiation occurs, neuronal architecture in the absence of myocytes is similar to that in their presence, either in standard or in calcium-free medium, although neurite extension is enhanced by the absence of calcium. (3) Conditioned medium (CM) experiments additionally demonstrate that the orientation of neurite outgrowth to myocyte-derived cues is calcium dependent, although the production of directional cues by myocytes is calcium independent. PMID- 8515254 TI - Identification of molecules in a muscle extracellular matrix extract that promotes process outgrowth from cultured adult frog motoneurons. AB - The molecular composition of the substrate on which neurons are cultured is critical for their attachment, survival, and extension of processes. The aim of the present experiments was to characterize the molecules in an extracellular matrix (ECM) extract that promotes the outgrowth of processes from cultured adult frog motoneurons. An extract was made of skeletal muscle ECM and tested as a substrate for cultured motoneurons. The average total process length of motoneurons cultured on this crude ECM extract is greater than when the neurons are cultured on concanavalin A, poly-L-lysine or mouse tumor (EHS) laminin. Gel filtration of the ECM extract yielded fractions with an increased specific activity for promoting process outgrowth. The most active fractions exhibit a single major polypeptide band of ca. 1 mD and two minor bands of ca. greater than 1 mD and 205 kD upon sodium dodecyl sulfate gel electrophoresis. Under reducing conditions, three major bands were seen of 340, 205, and 200 kD. Electron microscopy of rotary-shadowed ECM fractions showed macromolecules with a cross shaped structure similar to vertebrate and invertebrate laminin, a rod-like molecule resembling vertebrate and invertebrate collagen type IV, and a third molecule similar in appearance to vertebrate fibrillin. These results represent the first step in analyzing the role of substrate molecules in promoting neuromuscular reinnervation. PMID- 8515255 TI - Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting. AB - Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and up to 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat. PMID- 8515256 TI - Synaptic vesicle traffic: rush hour in the nerve terminal. PMID- 8515257 TI - 125I-ifenprodil: synthesis and characterization of binding to a polyamine sensitive site in cerebral cortical membranes. AB - The characteristics of binding sites in rat cerebral cortical synaptic membranes labeled by 125I-ifenprodil, a noncompetitive NMDA receptor antagonist, are described. 125I-ifenprodil was synthesized using Na125I in the presence of chloramine-T and purified by paper chromatography. Binding of the 125I-ligand was optimal at pH 7.7 in 5 mM Tris.HCl buffer. Equilibrium binding of 125I-ifenprodil was displaced by spermine (1 mM) but not by ifenprodil or its analogue, SL 82.0715 (both 16.7 microM). Zn2+, Ca2+, and Mg2+ inhibited specific binding of 125I-ifenprodil in a concentration-dependent manner, with IC50 values of 0.11, 1.1, and 1.7 mM, respectively. The dissociation constant (KD) for unlabeled ifenprodil determined by saturation binding was 205 nM. Scatchard plots of saturation data appeared curvilinear but were best described by a single-binding site model (Hill coefficient = 0.95), with a density of binding sites (Bmax) of 141 pmol/mg of protein. Binding of 125I-ifenprodil was inhibited by polyamines, with a rank potency order of spermine > spermidine > putrescine = 1,3 diaminopropane. The pattern of inhibition produced by spermidine was apparently competitive. Ifenprodil congeners also fully inhibited polyamine-sensitive binding of 125I-ifenprodil, with a rank potency order of ifenprodil > SL 82.0715 = tibalosine > nylidrin = isoxsuprine. It was found that sigma/antitussive agents partially inhibited specific binding, but inclusion of the sigma drug GBR 12909 had little effect on the binding of 125I-ifenprodil, suggesting this site was not involved. The binding site labeled by 125I-ifenprodil is polyamine sensitive, has a discrete pharmacological profile, and apparently is unrelated to the sigma site. PMID- 8515258 TI - Receptor-mediated endocytosis of a manganese complex of transferrin into neuroblastoma (SHSY5Y) cells in culture. AB - Exposure to manganese compounds often occurs as the result of industrial production or mining. Although manganese appears in traces in animal and human tissue and is essential to certain biological processes, it is also toxic. In humans and animals, toxicity is mainly associated with the nervous system. The mechanism underlying behavioral and biochemical alterations observed after manganese intoxication is not fully understood. We have shown that the manganese present in serum after exposure to manganese oxide is bound to transferrin as trivalent manganic ion. In this study of manganese uptake and storage we used a clone of human neuroblastoma cells (SHSY5Y). These cells differentiate and express catecholaminergic properties. Saturation binding analysis of the transferrin-manganese complex to the cells revealed a single class of binding sites, with an apparent KD of 13 +/- 1 nM and a density of 11,000 +/- 2,000 binding sites per cell. The complex was internalized in a temperature-dependent way and reached saturation after 2 h when approximately 2% of the added manganese had been internalized. About 80% of the internalized manganese was found in ferritin after 24 h of exposure. The results demonstrate that the transferrin receptor on SHSY5Y cells can bind and internalize a manganese-transferrin complex as efficiently as an iron-transferrin complex, although a saturation of the manganese uptake was achieved. PMID- 8515259 TI - Changes in sympathetic nerve terminals in the heart of cold-exposed rats. AB - Changes in sympathetic nerve terminals of the heart after varying periods of exposure of rats to 4 degrees C were investigated. Two indices were used for changes in the number of noradrenaline storage vesicles, i.e., vesicular dopamine beta-hydroxylase (DBH) activity and noradrenaline storage capacity. The latter was obtained after uptake of [3H]noradrenaline; endogenous content, uptake of exogenous noradrenaline, and degree of saturation of the vesicles were calculated using the specific activity of the [3H]noradrenaline. As a measure of tyrosine hydroxylase activity, whole ventricular noradrenaline, dopamine, and dihydroxyphenylacetic acid content were used. After 4 h of cold exposure there was an increase in vesicular endogenous noradrenaline content, uptake, storage capacity, and DBH activity as well as a large increase in whole ventricular dopamine. After 6 h in the cold, vesicular endogenous noradrenaline content, storage capacity, and DBH activity were decreased. The results suggest that during cold exposure there is an initial increase followed by a decrease in the number of functional vesicles in the nerve terminal, which could explain the fluctuations in the rate of noradrenaline release. PMID- 8515260 TI - 31P NMR relaxation does not affect the quantitation of changes in phosphocreatine, inorganic phosphate, and ATP measured in vivo during complete ischemia in swine brain. AB - Ischemia-induced changes in 31P NMR relaxation were examined in 16 piglets. NMR spectra were acquired under control conditions and during complete cerebral ischemia induced via cardiac arrest. Changes in T1 were assessed directly in six animals during control conditions and after 30-45 min of complete ischemia when changes in brain Pi levels had reached a plateau. The T1 for Pi did not change, i.e., 2.3 +/- 0.5 s during control conditions versus 2.4 +/- 1.0 s during ischemia. To evaluate phosphocreatine and ATP, two types of spectra, with a long (25-s) or short (1-s) interpulse delay time, were collected during the first 10 min of ischemia (n = 10). Both types of spectra showed the same time course of changes in phosphocreatine and ATP levels, implying that the T1 relaxation times do not change during ischemia. There were no changes in the linewidths of phosphocreatine, ATP, or Pi during ischemia, implying that the T2* values remain constant. Our results suggest that the 31P T1 and T2* for phosphocreatine, Pi, and ATP do not change during ischemia, and therefore changes in 31P NMR peak intensity accurately reflect changes in metabolite concentrations. PMID- 8515261 TI - Metabolism of arachidonic acid to epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and prostaglandins in cultured rat hippocampal astrocytes. AB - We have recently shown that brain slices are capable of metabolizing arachidonic acid by the epoxygenase pathway. The purpose of this study was to begin to determine the ability of individual brain cell types to form epoxygenase metabolites. We have examined the astrocyte epoxygenase pathway and have also confirmed metabolism by the cyclooxygenase and lipoxygenase enzyme systems. Cultured rat hippocampal astrocyte homogenate, when incubated with radiolabeled [3H]arachidonic acid, formed products that eluted in four major groups designated as R17-30, R42-50, R51-82, and R83-90 based on their retention times in reverse phase HPLC. These fractions were further segregated into as many as 13 peaks by normal-phase HPLC and a second reverse-phase HPLC system. The principal components in each peak were structurally characterized by gas chromatography/electron impact-mass spectrometry. Based on HPLC retention times and gas chromatography/electron impact-mass spectrometry analysis, the more polar fractions (R17-30) contained prostaglandin D2 as the major cyclooxygenase product. Minor products included 6-keto prostaglandin F1 alpha, prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2. Fractions R42-50, R51-82, and R83-90 contained epoxygenase and lipoxygenase-like products. The major metabolite in fractions R83-90 was 5,6-epoxyeicosatrienoic acid (EET). Fractions R51-82 contained 14,15- and 8,9-EETs, 12- and 5-hydroxyeicosatetraenoic acids, and 8,9- and 5,6-dihydroxyeicosatrienoic acids (DHETs). In fractions R42-50, 14,15-DHET was the major product. When radiolabeled [3H]14,15-EET was incubated with astrocyte homogenate, it was rapidly metabolized to [3H]14,15-DHET. The metabolism was inhibited by submicromolar concentration of 4-phenylchalcone oxide, a potent inhibitor of epoxide hydrolase activity. Formation of other polar metabolites such as triols or epoxy alcohols from 14,15-DHET was not observed. In conclusion, astrocytes readily metabolize arachidonic acid to 14,15-EET, 5,6-EET, and their vicinal-diols. Previous studies suggest these products may affect neuronal function and cerebral blood flow. PMID- 8515262 TI - Analysis of a segment of the human glial fibrillary acidic protein gene that directs astrocyte-specific transcription. AB - To understand astrocyte-specific transcription, we have been studying the human gfa gene. This gene encodes glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed primarily in astrocytes. A survey of the gfa 5' flanking region showed it to contain several segments that contribute to expression of a chloramphenicol acetyltransferase reporter gene in transfected cells. The most active of these was the 124-bp B region, which spans bp -1612 to 1489. We have now used site-directed mutagenesis to analyze this region in greater detail, and show that the B region itself contains several important elements. The most crucial of these is a consensus AP-1 sequence, the binding site for the Fos and Jun families of transcription factors. The presence of members of both these families in the glial fibrillary acidic protein-expressing U251 cell line used for our transfection studies was verified by gel mobility shift experiments. This is the first demonstration of the functioning of a specific transcription factor site for astrocytes, and provides a focus for future studies of glial fibrillary acidic protein regulation during development and reactive gliosis. PMID- 8515263 TI - Cationic and anionic requirements for the binding of 2 beta-carbomethoxy-3 beta (4-fluorophenyl)[3H]tropane to the dopamine uptake carrier. AB - The present study reports the ion dependency of 2 beta-carbomethoxy-3 beta-(4 fluorophenyl)[3H]tropane ([3H]CFT) binding to the dopamine transporter in the rat striatum. The results indicate that [3H]CFT binding to synaptosomal P2 membranes requires low concentrations of Na+ (peak binding between 20 and 50 mM Na+), is stimulated by phosphate anion or I-, but is unaffected or only slightly affected by F-, Cl-, Br-, NO3-, or SO(4)2-. Concentrations of Na+ of > 50 mM become inhibitory except in the presence of I-, which shifts peak binding levels toward higher Na+ concentrations and also elevates the peak binding level. K+ strongly decreased [3H]CFT binding with a shallow inhibition curve, and Na+ could not overcome this effect. Saturation analysis of [3H]CFT binding revealed a single binding site changing its affinity for CFT depending on the concentration of sodium phosphate buffer (6, 10, 30, 50, 130, or 200 mM; 1 mM plus 49 mM NaCl versus 10 mM plus 40 mM NaCl; or 1 mM plus 129 mM NaI versus 10 mM plus 120 mM NaI). No differences were observed in the density of CFT binding sites between any of the conditions examined. PMID- 8515264 TI - Extracellular neuroactive amino acids in the rat striatum during ischaemia: comparison between penumbral conditions and ischaemia with sustained anoxic depolarisation. AB - Changes in the extracellular levels of excitatory and inhibitory amino acid transmitters were studied in the rat striatum during penumbral ischaemia using intracerebral microdialysis. Effects of penumbral forebrain ischaemia were compared with those of ischaemia with sustained anoxic depolarisation and K+ (100 mM). Comparisons were also made between different groups of animals at 2 and 24 h after dialysis probe implantation. The K+ stimulus did not provoke any release of excitatory amino acids in the 24-h group, probably reflecting a decrease of functional synapses adjacent to the probe. During 30 min of penumbral ischaemia, excitatory amino acids did not reach critical concentrations in the extracellular fluid, and increases in levels of inhibitory/modulatory amino acids were similar. On the other hand, severe transient ischaemia resulted in massive synchronous release of many neuroactive excitatory and inhibitory compounds, in both the 2- and 24-h groups. These and other data suggest that changes during severe ischaemia may arise from both neurotransmitter and metabolic pools. It is concluded that ischaemic damage in the penumbra may not be related to extracellular neuroactive amino acid changes generated within this region. PMID- 8515265 TI - The deduced amino acid sequences of human platelet and frontal cortex monoamine oxidase B are identical. AB - Monoamine oxidases (MAOs) A and B play important roles in the metabolism of neuroactive, vasoactive amines. Human platelets contain only MAO B, often used as an indicator of brain MAO B. The validity of this model remained to be evaluated. This report describes the molecular cloning of human MAO B from frontal cortex and platelets. Two overlapping PCR-amplified clones of human platelet MAO B and four PCR-amplified clones of human frontal cortex MAO B covering the entire coding region were sequenced using five internal oligomers and M13 reverse and forward primers. The nucleotide sequences of human MAO B cDNA from platelet and frontal cortex were identical to that of human liver MAO B except for three nucleotides that differed in frontal cortex: nucleotides 440 A-->G, 794 C-->T, and 825 C-->T. Whether or not these differences are artifactual, all three represent silent mutations, which would not alter the amino acid of the encoded polypeptides. Thus, the deduced amino acid sequences of MAO B from frontal cortex, platelet, and liver are identical. These findings indicate the validity of using platelet MAO B mRNA as a marker for brain MAO B and provide a new approach to study the role of brain MAO B in humans. PMID- 8515266 TI - Phosphorylation modulates calpain-mediated proteolysis and calmodulin binding of the 200-kDa and 160-kDa neurofilament proteins. AB - The effects of enzymatic dephosphorylation on neurofilament interaction with two calcium-binding proteins, calpain and calmodulin, were examined. Dephosphorylation increased the rate and extent of 200-kDa neurofilament protein proteolysis by calpain. In contrast, dephosphorylation of the 160-kDa neurofilament protein did not alter the rate or extent of calpain proteolysis. However, the calpain-induced breakdown products of native and dephosphorylated 160-kDa neurofilament protein were different. Dephosphorylation did not change the proteolytic rate, extent, or breakdown products of the 68-kDa neurofilament protein. Calmodulin binding to the purified individual 160- and 200-kDa neurofilament proteins was increased following dephosphorylation. These results suggest that phosphorylation may regulate the metabolism and function of neurofilaments by modulating interactions with the calcium-activated proteins calpain and calmodulin. PMID- 8515267 TI - Protective effect of hypothermia on hippocampal injury after 30 minutes of forebrain ischemia in rats is mediated by postischemic recovery of protein synthesis. AB - Regional protein synthesis of brain was measured by quantitative autoradiography in normo- and hypothermic rats submitted to 30 min of four-vessel occlusion. The tracer, [14C]leucine, was applied by controlled intravenous infusion to achieve constant plasma specific activity, and the admixture by proteolysis of unlabeled amino acids to the brain amino acid precursor pool was corrected by measuring the ratio of the labeled-to-unlabeled leucine distribution space in plasma and brain. In normothermic rats preischemic protein synthesis rate was 16.0 +/- 3.2, 9.2 +/- 3.4, 15.5 +/- 2.8, and 15.5 +/- 3.1 nmol of leucine/g/min (mean +/- SD) in the frontal cortex, striatum, hippocampal CA1 sector, and thalamus, respectively. After 30 min of ischemia at a constant brain temperature of 36 degrees C and a recirculation time of 1 h, protein synthesis was reduced in these regions to 6, 9, 8, and 36%, respectively. With ongoing recirculation, protein synthesis gradually returned to normal within 3 days in all areas except in the stratum pyramidale of the hippocampal CA1 sector where inhibition of neuronal protein synthesis was irreversible. Lowering of brain temperature to 30 degrees C during ischemia did not prevent the early global postischemic depression of protein synthesis, but promoted recovery to or above normal within 6 h in all areas including the stratum pyramidale of the CA1 sector. Improvement of protein synthesis in the CA1 sector was associated with improved neuronal survival, which increased from 1% in the normothermic to 69% in the hypothermic animals. These observations suggest that the protective effect of mild hypothermia on ischemic injury of the hippocampal CA1 sector is mediated by the reversal of the postischemic inhibition of protein synthesis. PMID- 8515268 TI - K-252a and staurosporine promote choline acetyltransferase activity in rat spinal cord cultures. AB - The protein kinase inhibitor K-252a increased choline acetyltransferase (ChAT) activity in rat embryonic spinal cord cultures in a dose-dependent manner (EC50 of approximately 100 nM) with maximal stimulatory activity at 300 nM resulting in as much as a fourfold increase. A single application of K-252a completely prevented the marked decline in ChAT activity occurring over a 5-day period following culture initiation. Of 11 kinase inhibitors, only the structurally related inhibitor staurosporine also increased ChAT activity (EC50 of approximately 0.5 nM). Effective concentrations of K-252a were not cytotoxic or mitogenic and did not alter the total protein content of treated cultures. Insulin-like growth factor I, basic fibroblast growth factor, ciliary neurotrophic factor, and leukemia inhibitory factor yielded dose-dependent increases in ChAT activity in spinal cord cultures. The combination of K-252a with insulin-like growth factor-I or basic fibroblast growth factor increased ChAT activity up to eightfold over that of untreated controls, which was greater than that observed with each compound alone. K-252a combined with ciliary neurotrophic factor or leukemia inhibitory factor demonstrated no additive or synergistic effects on ChAT activity. These results suggest that there are multiple mechanisms for the regulation of ChAT activity in spinal cord cultures. The enhancement of spinal cord ChAT activity by K-252a and staurosporine defines a new neurotrophic activity for these small organic molecules and raises the possibility that they may activate some regulatory elements in common with the ciliary neurotrophic factor and leukemia inhibitory factor family of neurotrophic proteins. PMID- 8515269 TI - The triplet of lysine residues (Lys724-Lys725-Lys726) of Alzheimer's amyloid precursor protein plays an important role in membrane anchorage and processing. AB - One of the pathological changes of Alzheimer's disease is the deposit of beta/A4 protein, which is derived from Alzheimer amyloid precursor protein (APP). In the secretory pathway, APP is cleaved at an internal region of beta/A4 protein by a hypothetical enzyme "secretase." Our previous study showed that the site of cleavage of APP by secretase is determined by the length from the membrane spanning region. To investigate the role of the transmembrane region in APP secretion, we constructed the mutations of triplet lysine residues (Lys724-Lys725 Lys726), which are located just in the carboxyl region after the proposed membrane domain. The mutations were as follows: VVK, Val724-Val725-Lys726; LLI, Leu724-Leu725-Ile726; and EEE, Glu724-Glu725-Glu726. Wild-type APP and mutant APPs were expressed transiently in COS-1 cells by cDNA transfection. The hydrophobic mutant VVK and LLI were processed and secreted in a way similar to that of the wild-type APP, although the rate of secretion was decreased. The acidic mutant EEE was not secreted into medium. Proteinase K treatment and cell surface biotinylation of the COS-1 cells expressing APP revealed that APP was located in the plasma membrane with a short intracellular carboxyl region. However, EEE was completely digested by proteinase K treatment, which suggested that the whole residues of this mutant are located at the outer surface of the cell, including its proposed membrane domain and carboxyl region. This mutant was not cleaved at all by secretase. These findings suggested that the triplet lysine residues of AP after the predicted membrane spanning domain play an important role in the membrane anchorage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515270 TI - Functional analysis of conserved histidines in choline acetyltransferase by site directed mutagenesis. AB - The choline acetyltransferase (ChAT) reaction involves the transfer of the acetyl group of acetyl-CoA to choline, in which an active site histidine is believed to act as a general acid/base catalyst. A comparison of the deduced amino acid sequences of the enzyme from Drosophila, pig, rat, and Caernohabditis elegans revealed three conserved histidines: Drosophila His268, His393, and His426. Each of these histidines was replaced by a leucine and a glutamine, and the kinetic properties of each of the recombinant mutant enzymes were determined. The mutations yielded active His268Leu-ChAT, His268Gln-ChAT, and His393Gln-ChAT and inactive His393Leu-ChAT, His426Leu-ChAT, and His426Gln-ChAT. The kinetic constants Km(CoA), Km(acetylcholine), and Vmax were essentially the same for all of the active mutants. When the integrity of the CoASAc binding site was investigated in the inactive mutants, the data suggested that the binding site in His393Leu-ChAT is disrupted but conserved in His426Leu-ChAT and His426Gln-ChAT. These results suggest that His426 is an essential catalytic residue and could serve as an acid/base catalyst. PMID- 8515271 TI - Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain. AB - The effect of pentobarbital on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brains was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brains, HSP70 mRNA was scarcely present, whereas HSC70 mRNA was present in most cell populations. After a 5-min occlusion of bilateral common carotid arteries, HSP70 and HSC70 mRNAs were induced together in several cells and were especially dense in hippocampal dentate granule cells at 3 h, but the strong hybridization of the mRNAs continued only in hippocampal CA1 cells by 2 days. At 7 days after the ischemia, CA1 neuronal cell death was apparent, and the HSP70 mRNA disappeared and HSC70 mRNA content returned to the sham level, except for in the CA1 cells. Pretreatment with pentobarbital (40 mg/kg, i.p.) greatly reduced or inhibited the induction of HSP70 and HSC70 mRNAs at both early (3-h) and late (2-day) phases after ischemia. The drug also prevented CA1 cell death at 7 days along with the maintenance of expression of HSC70 mRNA at the sham control level. Hypothermic effects of pentobarbital were noted at 30 and 60 min after the reperfusion, whereas at 2 h there was no statistical significance between the control and drug-treated groups. The great reduction of HSP70 and HSC70 mRNA induction at both early and late phases after ischemia suggests that pentobarbital reduces intra-and/or postischemic stress and may protect CA1 cells from ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515272 TI - Ouabain releases striatal polyamines in vivo independently of N-methyl-D aspartate receptor activation. AB - Intrastriatally infused ouabain (200 or 1,000 microM) markedly increased the extracellular levels of striatal spermidine and spermine in dialysis experiments in halothane-anesthetized rats. The effects of ouabain (1 mM) on spermidine release were rapid and unaffected by local infusion of the competitive N-methyl-D aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 100 microM) or by systemically administered MK-801 (0.3 mg/kg i.p.), both of which treatments markedly inhibit the effects of intrastriatally administered NMDA. The peak effects of ouabain (1 mM) on spermine release were delayed with respect to those on spermidine release, or to the effects of NMDA, and were also insensitive to locally administered CPP (100 microM). However, systemically administered MK-801 (0.3 mg/kg i.p., 30 min before the striatal infusion of drugs), which totally inhibits the effects of NMDA, or CPP (10 mg/kg i.p.; 30 min before the striatal infusion of drugs) partially inhibited the effects of ouabain on spermine release, suggesting partial mediation of the delayed effects of ouabain on spermine release by indirect NMDA-receptor activation. Despite partial sensitivity of ouabain-induced spermine release to systemically administered NMDA antagonists, both spermidine and spermine can be released in vivo by sodium-pump inhibition, independently of NMDA-receptor activation. PMID- 8515273 TI - Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat. AB - Scopolamine (0.15 mg/kg), a muscarinic antagonist, when administered during training or at a discrete 6-h posttraining time point, is demonstrated to inhibit the recall of a step-down passive avoidance response when tested at 24 and 48 h after task acquisition. Nefiracetam (3 mg/kg), a piracetam-related nootropic, when given with scopolamine during training tended to improve task recall, and this effect was more pronounced when given at the 6-h posttraining time. Co administration of nefiracetam with scopolamine was not necessary to achieve the antiamnesic action, as nefiracetam given during training significantly improved the memory deficits produced by scopolamine at the 6-h posttraining time. The paradigm-specific increase in hippocampal neural cell adhesion molecule sialylation, which is observed during consolidation of a passive avoidance response, was attenuated by the presence of scopolamine during training and at the 6-h posttraining time, and this effect was reversed by co-administration of nefiracetam, albeit in a paradigm-independent manner. These results suggest nefiracetam exerts a neurotrophic action that protects memory consolidation from drug interventive insults. PMID- 8515274 TI - Reduced clearance of exogenous dopamine in rat nucleus accumbens, but not in dorsal striatum, following cocaine challenge in rats withdrawn from repeated cocaine administration. AB - We investigated whether changes in the dopamine transporter in the nucleus accumbens or striatum are involved in cocaine-induced behavioral sensitization by using in vivo electrochemistry to monitor the clearance of locally applied dopamine in anesthetized rats. Rats were injected with cocaine-HCl (10 mg/kg i.p.) or saline daily for 7 consecutive days and then withdrawn for 7 days. Pressure ejection of a finite amount of dopamine at 5-min intervals from a micropipette adjacent to the electrochemical recording electrode produced transient and reproducible dopamine signals. After a challenge injection of cocaine (10 mg/kg i.p.), the signals in the nucleus accumbens of cocaine-treated animals became prolonged and the clearance rate of the dopamine decreased, indicating significant inhibition of the dopamine transporter. In contrast, simultaneous measurements in the dorsal striatum indicated a transient increase in both the amplitude of the signals and the clearance rate of the dopamine. The signals in both brain regions in the saline-treated animals given the cocaine challenge were similar to those in untreated animals given an acute injection of cocaine (10 mg/kg i.p.) or saline. Behaviorally, not all of the cocaine-treated animals were sensitized; however, both sensitized and nonsensitized animals displayed similar changes in dopamine clearance rate. Quantitative autoradiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine and the density of binding sites were similar in cocaine- and saline-treated rats. The decrease in dopamine clearance rate observed in the nucleus accumbens of the cocaine-treated rats after a challenge injection of cocaine is consistent with increased dopaminergic transmission, but does not appear to be sufficient in itself for producing behavioral sensitization. PMID- 8515275 TI - Investigations into the adenosine outflow from hippocampal slices evoked by ischemia-like conditions. AB - The characteristics of adenosine and inosine outflow evoked by 5 min of ischemia like conditions in vitro (superfusion with glucose-free Krebs solution gassed with 95% N2/5% CO2) were investigated on rat hippocampal slices. The viability of the slices after "ischemia" was evaluated by extracellular recording of the evoked synaptic responses in the CA1 region. The evoked dendritic field potentials were abolished after 5 min of superfusion under "ischemia" but a complete recovery occurred after 5 min of reperfusion with normal oxygenated Krebs solution. No recovery took place after 10 min of "ischemia." The addition of the adenosine A1 receptor antagonist 8-phenyltheophylline to the superfusate antagonized the depression of the evoked field potentials caused by 5 min of "ischemia." Five minutes of "ischemia" brought about a six- and fivefold increase in adenosine and inosine outflow, respectively, within 10 min. Tetrodotoxin reduced the outflow of adenosine and inosine by 42 and 33%, respectively, whereas the removal of Ca2+ caused a further increase. The NMDA receptor antagonist D(-) 2-amino-7-phosphonoheptanoic acid and the non-NMDA antagonist 6,7 dinitroquinoxaline-2,3-dione brought about small, not statistically significant decreases of adenosine and inosine outflow. The glutamate uptake inhibitor dihydrokainate did not affect the outflow of adenosine and inosine. Inhibition of ecto-5'-nucleotidase by alpha,beta-methylene ADP and GMP did not affect basal adenosine outflow but potentiated "ischemia"-evoked adenosine outflow. It is concluded that ischemia-like conditions in vitro evoke a Ca(2+)-independent adenosine and inosine outflow, through a mechanism that partly depends on propagated nervous activity but does not involve excitatory amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515276 TI - Lipid and fatty acid composition of brain tissue from adrenoleukodystrophy patients. AB - White matter and active plaque tissue from adrenoleukodystrophy (ALD) patients were analysed for lipid class and fatty acid compositions and the results compared with white matter from normal brain. ALD white matter was characterised by increased levels of cholesteryl esters and decreased levels of phosphatidylethanolamine, including phosphatidylethanolamine plasmalogen, in comparison with normal brain white matter. In addition to even higher levels of cholesteryl esters, ALD plaque tissue had reduced levels of cerebrosides as well as phosphatidylethanolamines. The loss of phosphatidylethanolamine plasmalogen is indicative of early demyelination. Total lipid from ALD white matter and ALD plaque tissue contained nearly five times and seven times, respectively, more 26:0 than total lipid from normal brain white matter. The 26:0 in ALD white matter was elevated in all lipid classes except phosphatidylinositol, but was located mainly in cerebrosides, phosphatidylcholine, sphingomyelin, and sulfatides. Most of the 26:0 in ALD plaque tissue was present in cholesteryl esters, followed by phosphatidylcholine and sphingomyelin, with reduced amounts in cerebrosides as compared with ALD white matter. The results are consistent with an initial accumulation of very-long-chain fatty acids in ALD white matter, primarily in sphingolipids and phosphatidylcholine, and subsequent accumulation of very-long-chain fatty acids in cholesteryl esters during demyelination. In addition, it was notable that the sphingolipids, especially sphingomyelin in ALD brain, had decreased levels of 24:1 and increased levels of 18:0, as well as increased levels of very-long-chain fatty acids. The extent to which the data shed light on mechanisms of demyelination in ALD is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515277 TI - Alpha 1-antichymotrypsin binding to Alzheimer A beta peptides is sequence specific and induces fibril disaggregation in vitro. AB - The serine protease inhibitor alpha 1-antichymotrypsin (ACT) consistently colocalizes with amyloid deposits of Alzheimer's disease (AD) and may contribute to the generation of amyloid proteins and/or physically affect fibril assembly. AD amyloid fibrils are composed primarily of A beta, which is a proteolytic fragment of the larger beta-amyloid precursor protein. Using negative-stain and immunochemical electron microscopy, we have investigated the binding of ACT to the fibrils formed by four synthetic A beta analogues corresponding to the wild type human 1-40 sequence [Hwt(1-40)], a 1-40 peptide [HDu(1-40)] containing the Glu22-->Gln mutation found in hereditary cerebral hemorrhage with amyloidosis of the Dutch type, the N-terminal 1-28 residues [beta(1-28)], and an internal fragment of A beta containing residues 11-28 [beta(11-28)]. Each of these peptide analogues assembled into 70-90-A-diameter fibrils resembling native amyloid and, except for beta(11-28), bound ACT, as indicated by the appearance of 80-100-A globular particles that adhered to preformed fibrils and that could be decorated with anti-ACT antibodies. Under the conditions used, ACT binding destabilized the in vitro fibrils and produced a gradual dissolution of the macromolecular assemblies into constituent filaments and shorter fragments. The internal fragment (11-28) did not exhibit ACT binding or any structural changes. These results suggest that a specific sequence likely contained within the N-terminal 10 residues of A beta is responsible for the formation of the ACT-amyloid complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515278 TI - Comparison of the promoter region of the human and porcine choline acetyltransferase genes: localization of an important enhancer region. AB - Genomic clones of human and porcine choline acetyltransferase were obtained by screening genomic libraries with synthetic oligonucleotides. The human and porcine genes exhibit significant conservation of both their intron/exon structure and the nucleotide sequence in their 5' flanking regions. However, the two genes differ in several respects, including the absence of a "TATA" box in the human gene and differences in the position of the methionine start codon. Analysis of the promoter region of the two genes has led to the localization of an enhancer element that appears necessary for efficient transcription of the gene. PMID- 8515279 TI - Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. AB - Nuclear magnetic resonance (NMR) was used to study the metabolic pathways involved in the conversion of glucose to glutamate, gamma-aminobutyrate (GABA), glutamine, and aspartate. D-[1-13C]Glucose was administered to rats intraperitoneally, and 6, 15, 30, or 45 min later the rats were killed and extracts from the forebrain were prepared for 13C-NMR analysis and amino acid analysis. The absolute amount of 13C present within each carbonatom pool was determined for C-2, C-3, and C-4 of glutamate, glutamine, and GABA, for C-2 and C 3 of aspartate, and for C-3 of lactate. The natural abundance 13C present in extracts from control rats was also determined for each of these compounds and for N-acetylaspartate and taurine. The pattern of labeling within glutamate and GABA indicates that these amino acids were synthesized primarily within compartments in which glucose was metabolized to pyruvate, followed by decarboxylation to acetyl-CoA for entry into the tricarboxylic acid cycle. In contrast, the labeling pattern for glutamine and aspartate indicates that appreciable amounts of these amino acids were synthesized within a compartment in which glucose was metabolized to pyruvate, followed by carboxylation to oxaloacetate. These results are consistent with the concept that pyruvate carboxylase and glutamine synthetase are glia-specific enzymes, and that this partially accounts for the unusual metabolic compartmentation in CNS tissues. The results of our study also support the concept that there are several pools of glutamate, with different metabolic turnover rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515280 TI - Serotonin modulates nicotinic responses of adrenal chromaffin cells. AB - 5-Hydroxytryptamine (5-HT) specifically and reversibly inhibits nicotine-induced currents and catecholamine release in bovine adrenal chromaffin cells in culture. Pharmacological analysis indicates that the inhibition is not mediated by known 5 HT receptor subtypes. The inhibition is noncompetitive over a range of nicotine concentrations between 1 and 100 microM. Preincubation with either 5-HT or substance P significantly protects the response from nicotine-induced desensitization. It is concluded that 5-HT inhibits nicotinic acetylcholine receptors on bovine adrenal chromaffin cells, probably by binding to a noncompetitive site on the receptor itself. Because both blood and the chromaffin cells contain 5-HT, the inhibition provides an opportunity for negative control of catecholamine secretion from the adrenals. PMID- 8515281 TI - Acute neurite retraction elicited by diverse agents is prevented by genistein, a tyrosine kinase inhibitor. AB - The retraction of axonal branches is a prominent feature of nervous system development and function. Although various biological and pathological signals can elicit retraction, little is known regarding their underlying mode of action. An in vitro assay using NG108-15 cells was used to demonstrate that rapid-onset neurites exposed acutely to trypsin, serum, lysophosphatidic acid, extracellular ATP, the phorbol ester phorbol 12-myristate 13-acetate, and nocodazole were all protected from retraction by the tyrosine kinase inhibitor genistein. This finding indicates that a common (genistein-sensitive) cellular event is involved in integrating the influence of multiple extrinsic and intrinsic signals and in regulating whether or not neurites will execute a retraction response. PMID- 8515282 TI - Protein S, an antithrombotic factor, is synthesized and released by neural tumor cells. AB - Protein S, an anticoagulant factor in the protein C antithrombotic pathway, was found to be synthesized and released by six tumor cell lines of neural origin by western blotting and ELISA. The rate of synthesis ranged from three- to 11-fold higher than that of a microvascular endothelial cell line and 36-144% that of a hepatoma cell line. The secreted protein S displayed specific anticoagulant activity similar to that of purified plasma protein S, implying that it was fully gamma-carboxylated. Ten primary brain tumor tissues also expressed protein S antigen, as shown by western blot analysis. Expression of anticoagulantly active protein S by neural cells raises important questions concerning possible physiologic roles for this multidomain protein beyond its function in control of thrombosis. PMID- 8515283 TI - Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex. AB - We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor. PMID- 8515284 TI - Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. AB - A putative endogenous cannabinoid ligand, arachidonylethanolamide (termed "anandamide"), was isolated recently from porcine brain. Here we demonstrate that this compound is a specific cannabinoid agonist and exerts its action directly via the cannabinoid receptors. Anandamide specifically binds to membranes from cells transiently (COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carrying the cannabinoid receptor DNA but not to membranes from control nontransfected cells. Moreover, anandamide inhibited the forskolin stimulated adenylate cyclase in the transfected cells and in cells that naturally express cannabinoid receptors (N18TG2 neuroblastoma) but not in control nontransfected cells. As with exogenous cannabinoids, the inhibition by anandamide of the forskolin-stimulated adenylate cyclase was blocked by treatment with pertussis toxin. These data indicate that anandamide is an endogenous agonist that may serve as a genuine neurotransmitter for the cannabinoid receptor. PMID- 8515285 TI - Gangliosides inhibit platelet-derived growth factor-stimulated receptor dimerization in human glioma U-1242MG and Swiss 3T3 cells. AB - We previously showed that gangliosides inhibit DNA synthesis in Swiss 3T3 cells stimulated with platelet-derived growth factor (PDGF) in a dose-responsive manner. This correlated with the inhibitory effects of several gangliosides (except GM3) on tyrosine phosphorylation of the PDGF receptor (PDGFR). [35S]Methionine-labeled Swiss 3T3 cells were incubated either with or without gangliosides and stimulated with PDGF, and proteins were cross-linked with bis(sulfosuccinimidyl) suberate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that two protein bands (170 and 350 kDa) were specifically immunoprecipitated with an anti-PDGFR antibody. Using both Swiss 3T3 and human glioma U-1242MG cells, western blots with anti-PDGFR and anti phosphotyrosine antibodies confirmed that these bands were the PDGFR monomer and dimer, respectively, and that phosphotyrosine was present in these bands only after cells were stimulated with PDGF. Of the gangliosides tested, GM1, GM2, GD1a, GD1b, GD3, and GT1b, but not GM3, inhibited the formation of the 350-kDa band. These results demonstrate that all gangliosides tested, except GM3, probably inhibit PDGF-mediated growth by preventing dimerization of PDGFR monomers. Loss of more complex gangliosides in human gliomas would permit unregulated activation of the PDGFR, contributing to uncontrolled growth stimulation. We propose that ganglioside inhibition of receptor dimerization is a novel mechanism for regulating and coordinating several trophic factor-mediated cell functions. PMID- 8515286 TI - Aurintricarboxylic acid protects hippocampal neurons from NMDA- and ischemia induced toxicity in vivo. AB - The polymeric dye aurintricarboxylic acid (ATA) has been shown to protect various cell types from apoptotic cell death, reportedly through inhibition of a calcium dependent endonuclease activity. Recent studies have indicated that there may be some commonalities among apoptosis, programmed cell death, and certain other forms of neuronal death. To begin to explore the possibility of common biochemical mechanisms underlying ischemia- or excitotoxin-induced neuronal death and apoptosis in vivo, gerbils or rats subjected to transient global ischemia or NMDA microinjection, respectively, received a simultaneous intracerebral infusion of ATA or vehicle. As a biochemical marker of neuronal death, spectrin proteolysis, which is mediated by activation of calpain I, was measured in hippocampus after 24 h. ATA treatment resulted in a profound reduction of both NMDA- and ischemia-induced spectrin proteolysis, consistent with the possibility of some common mechanism in apoptosis and other forms of neuronal death in vivo. PMID- 8515287 TI - Mobilization of a vesamicol-insensitive pool of acetylcholine from a sympathetic ganglion by ouabain. AB - These experiments investigate the release of transmitter from the perfused superior cervical ganglia of cats induced by ouabain in the absence or presence of 2-(4-phenylpiperidino)cyclohexanol (vesamicol), a blocker of acetylcholine (ACh) uptake. Ouabain, perfused through the ganglia, released ACh in a Ca(2+) dependent way. Vesamicol caused some inhibition of the release of ACh by ouabain; however, under this condition, the Na+,K(+)-ATPase inhibitor released five times more transmitter than did preganglionic stimulation at 5 Hz. Also, when ganglia exposed to vesamicol were depleted of the impulse-releasable pool of ACh, subsequent perfusion with ouabain released ACh, and this included ACh newly synthesized in the presence of vesamicol; this phenomenon could be inhibited by the lack of Ca2+ and presence of EGTA, and was completely abolished by perfusion with a medium containing 18 mM Mg2+. To test whether the release of this vesamicol-insensitive Ca(2+)-dependent pool by ouabain is associated with a decrease in the number of synaptic vesicles, ganglia treated with the ATPase inhibitor after the depletion of the impulse-releasable pool of ACh were fixed for electron microscopy. In the presence of Ca2+, coincident with the release of the vesamicol-insensitive pool of ACh, nerve terminals were almost depleted of synaptic vesicles; ganglia treated similarly, but with medium containing 18 mM Mg2+ instead of Ca2+, were not depleted of synaptic vesicles. These results suggest that ouabain releases a vesamicol-insensitive pool of ACh from the sympathetic ganglion and also support the notion that this compartment is vesicular and its exocytosis depends on extracellular Ca2+. It is suggested that empty-vesicle recycling in the presence of vesamicol restricts mobilization of full vesicles to release sites. PMID- 8515288 TI - Corticosterone exacerbates kainate-induced alterations in hippocampal tau immunoreactivity and spectrin proteolysis in vivo. AB - Aberrant elevations in intracellular calcium levels, promoted by the excitatory amino acid glutamate, may be a final common mediator of the neuronal damage that occurs in hypoxic-ischemic and seizure disorders. Glutamate and altered neuronal calcium homeostasis have also been proposed to play roles in more chronic neurodegenerative disorders, including Alzheimer's disease. Any extrinsic factors that may augment calcium levels during such disorders may significantly exacerbate the resulting damage. Glucocorticoids (GCs), the adrenal steroid hormones released during stress, may represent one such extrinsic factor. GCs can exacerbate hippocampal damage induced by excitotoxic seizures and hypoxia ischemia, and we have observed recently that GCs elevate intracellular calcium levels in hippocampal neurons. We now report that the excitotoxin kainic acid (KA) can elicit antigenic changes in the microtubule-associated protein tau similar to those seen in the neurofibrillary tangles of Alzheimer's disease. KA induced a transient increase in the immunoreactivity of hippocampal CA3 neurons towards antibodies that recognize aberrant forms of tau (5E2 and Alz-50). The tau immunoreactivity appeared within 3 h of KA injection, preceded extensive neuronal damage, and subsequently disappeared as neurons degenerated. KA also caused spectrin breakdown, indicating the involvement of calcium-dependent proteases. Physiological concentrations of corticosterone (the species-typical GC of rats) enhanced the neuronal damage induced by KA and, critically, enhanced the intensity of tau immunoreactivity and spectrin breakdown. Moreover, the GC enhancement of spectrin proteolysis was prevented by energy supplementation, supporting the hypothesis that GC disruption of calcium homeostasis in the hippocampus is energetic in nature. Taken together, these findings demonstrate that neurofibrillary tangle-like alterations in tau, and spectrin breakdown, can be induced by excitatory amino acids and exacerbated by GCs in vivo. PMID- 8515289 TI - Role of omega-conotoxin GVIA-sensitive Ca2+ entry in angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding in bovine adrenal medullary cells. AB - The relative contributions of Ca2+ influx and intracellular Ca2+ mobilization were examined for angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding, which reflects the level of activated protein kinase C in bovine chromaffin cells. Angiotensin II receptors activate phospholipase C in chromaffin cells, leading to a short-lived mobilization of intracellular Ca2+. Angiotensin II stimulated [3H]phorbol 12,13-dibutyrate binding was largely blocked in Ca(2+) free buffer and by pretreatment with the Ca(2+)-channel blocker omega-conotoxin GVIA. The [3H]phorbol 12,13-dibutyrate binding response to [Sar1]angiotensin II also appeared to be voltage sensitive, as no additivity was observed with the response to the depolarizing agent 4-aminopyridine (3 mM). Threshold sensitivities of the extra- and intracellular Ca(2+)-mobilizing pathways to angiotensin II were similar, and all examined effects of angiotensin II in these cells were apparently mediated by losartan-sensitive (AT1-like) receptors. The dependence of angiotensin II-stimulated [3H]phorbol 12,13-dibutyrate binding on extracellular Ca2+ entry, in contrast to stimulation by other phospholipase C linked receptor agonists (bradykinin and methacholine), suggests that angiotensin II preferentially stimulates protein kinase C translocation to the plasma membrane, rather than to internal membranes, in bovine adrenal medullary cells. PMID- 8515290 TI - Control of intracellular growth of Mycobacterium fortuitum by human monocytes in vitro. AB - The ability of human monocytes to phagocytize and respond to infection by Mycobacterium fortuitum was tested using the method of Crowle and May. The monocytes were obtained from heparinized donor blood samples and separated from lymphocytes by adherence to plastic surfaces. M. fortuitum infection was performed immediately. Intracellular viability was indicated by colony forming units (CFU) done at 2 hour intervals. Monocytes were found to cause a rapid reduction in CFU during the first 2 hours of incubation. The rate of killing of M. fortuitum decreased thereafter but continued for the entire 8-hour study period. In parallel tests, ciprofloxacin and ofloxacin were added to the culture medium. Increased intracellular killing was observed with drug concentrations above 2 x MIC in both cases. Ofloxacin showed better antimycobacterial effects than ciprofloxacin. PMID- 8515291 TI - A preliminary study on the absorption of isometamidium chloride (Samorin) in the stomach and small intestine of rat. AB - The levels of absorption of isometamidium chloride (Samorin) in the stomach and intestine of the rat were determined because of problems usually associated with parenteral administration of the drug. The in situ loop method and in situ recirculation technique were used to determine the absorption of the drug in the stomach and intestine respectively. 54.8% of isometamidium chloride was absorbed in the stomach in 30 minutes while 2% was absorbed in the intestine in one hour. These results warrant the comparative study of the blood and tissue concentrations of isometamidium chloride following oral and parenteral administration. PMID- 8515292 TI - Penetration of ciprofloxacin into pleural fluid. AB - The penetration of oral 1000 mg/day ciprofloxacin into pleural fluid is investigated in 15 patients with exudative pleural effusion. After 4 days of ciprofloxacin therapy ciprofloxacin concentrations were measured in plasma and pleural exudate simultaneously by high-performance liquid chromatography (HPLC). Mean serum ciprofloxacin level was 1.58 +/- 0.91 mg/L and mean pleural exudate concentration was 1.00 +/- 0.59 mg/L. The concentrations achieved were all above the MIC90 of the majority of Gram-positive and Gram-negative pathogens. It is concluded that ciprofloxacin penetrates well into the pleural fluid. PMID- 8515293 TI - Piperacillin versus cefotetan as single-dose prophylaxis in abdominal hysterectomy: a prospective, randomized, multicenter study. AB - Five hundred and sixty-six women, consecutively admitted to nine different hospitals for elective abdominal hysterectomy, were randomized to receive a single 2 g i.v. dose of either cefotetan or piperacillin at induction of anesthesia. Five patients were excluded and 561 (287 given cefotetan and 274 given piperacillin) could be evaluated. In 10 patients (5 for each drug) the concentrations of either cefotetan or piperacillin in serum and subcutaneous tissue at the beginning and at the end of surgery and in uterus, salpinx and ovary samples, were microbiologically assessed. No significant differences could be found between cefotetan and piperacillin groups for any of the considered infectious complications (bacteremia, wound or vaginal cuff infection, pelvic cellulitis and febrile morbidity) nor for the pooled data (cefotetan group: 4.9%, piperacillin group: 5.8%, p:NS). As for the concentrations of prophylactic drugs, serum levels throughout surgery were found to be adequate. PMID- 8515294 TI - Chemoprophylaxis of bacterial infections in granulocytopenic patients with ciprofloxacin vs ciprofloxacin plus amoxicillin. AB - Ciprofloxacin was compared to ciprofloxacin plus amoxicillin as antibacterial prophylaxis in 53 evaluable patients with neutropenic episodes, because an oral penicillin may help to decrease the incidence of gram-positive infections. The two groups were randomized and evaluated in a number of febrile episodes, in days at fever/at risk, in mean interval of first febrile episode, in duration of antibiotic therapy and in causative organisms in febrile episodes. In conclusion, no significant difference was observed between the two groups in prevention of gram-positive bacteremias. PMID- 8515295 TI - Comparison of the efficacy and safety of ceftibuten and cefaclor in the treatment of pneumonia and bronchiectasis. AB - In a multicentre, international study of 187 adult patients with bacterial pneumonia or bronchiectasis, the safety and efficacy of a regimen of 200 mg ceftibuten administered twice-daily was compared with cefaclor given in a dosage of 500 mg three times a day. Of the 94 evaluable patients, 66 received ceftibuten and 28 received cefaclor. The overall bacteriological response was similar in the two treatment groups with elimination of the original pathogen in 91% and 89% of the patients receiving ceftibuten and cefaclor, respectively. The overall clinical response mirrored the bacteriological results with a successful clinical outcome in 92% of ceftibuten-treated patients compared with 93% in patients receiving cefaclor. Adverse experiences were, in general, few and mild, being reported in 8% and 17% of patients receiving ceftibuten and cefaclor, respectively. PMID- 8515296 TI - Risk/benefit in the treatment of children with imipenem-cilastatin for meningitis caused by penicillin-resistant pneumococcus. AB - A new case of pneumococcal meningitis in a child successfully treated with imipenem-cilastatin after failure of standard antibiotics is presented. Seizures, as the major adverse effect, were easily treated and no sequelae were later observed. The difficulty in distinguishing between seizures due to meningitis and those due to imipenem is discussed. We conclude that imipenem-cilastatin is a good alternative therapy in children's meningitis caused by pneumococcus resistant to standard antibiotics. PMID- 8515297 TI - Serum methotrexate (MTX) concentrations and prognosis in patients with osteosarcoma of the extremities treated with a multidrug neoadjuvant regimen. AB - The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515299 TI - In-vitro activity of ciprofloxacin and sixteen other antimicrobial agents against blood culture isolates. AB - The in-vitro antibacterial activities of seventeen antimicrobial agents including ampicillin, amikacin, Augmentin, aztreonam, cefazolin, cefuroxime, cefotaxime, ceftizoxime, ceftriaxone, ciprofloxacin, cloxacillin, erythromycin, gentamicin, penicillin G, piperacillin and vancomycin were compared against 100 Gram-negative and Gram-positive strains isolated from blood culture specimens received at the King Abdulaziz University Hospital (KAUH), in Jeddah, Saudi Arabia. The antibacterial susceptibility was determined by the minimal inhibitory concentration (MIC), using an agar dilution method. Ciprofloxacin exhibited the greatest activity, inhibiting 90% of the tested strains (MIC90) at a concentration ranging from < 0.015-0.5 mg/L. Against cloxacillin resistant or susceptible strains of Staphylococcus aureus and coagulase-negative staphylococci, ciprofloxacin had similar activity with MIC90 of 0.2 mg/L. Salmonella typhi and salmonella species which were resistant to ampicillin and augmentin remained sensitive to ciprofloxacin (MIC90 < 0.015-0.125) mg/L.). Against gentamicin sensitive and resistant Pseudomonas aeruginosa and Pseudomonas species, ciprofloxacin MIC90 was 0.5 and 1 mg/L respectively. Aminoglycosides, third generation cephalosporins, aztreonam and antipseudomonal penicillins, on the other hand, showed high MIC90 well above the obtainable serum concentrations against Enterobacteriaceae and Pseudomonas species. PMID- 8515298 TI - Amoxycillin/clavulanic acid: a review of its efficacy in over 38,500 patients from 1979 to 1992. AB - A review of the published literature detailing the clinical use of amoxycillin/clavulanic acid spanning the period 1979 to 1992 was undertaken to assess the clinical efficacy of the product and to determine whether any changes had occurred during this time. In the 415 publications meeting the selection criteria a total of over 38,500 patients were treated with amoxycillin/clavulanic acid. Analysis of the data confirms the efficacy of amoxycillin/clavulanic acid over a wide range of clinical indications and annual and triennial groupings of publications suggests that there has been little change in the clinical effectiveness of amoxycillin/clavulanic acid. Clinical efficacy rates (cure or improved) with amoxycillin/clavulanic acid were 88% and 92% in comparative and uncontrolled trials, respectively. Gastro-intestinal side effects are the most common adverse event but have been relatively infrequent. Amoxycillin/clavulanic acid should continue to be a useful antibiotic for upper and lower respiratory tract infections, skin structure infections, dental, head and neck infections, and selected urinary tract infections. PMID- 8515300 TI - Partial molar pregnancy associated with severe pregnancy-induced hypertension. AB - Although the natural history of pregnancies associated with complete hydatidiform mole has been well described, the clinical features of partial mole are less consistent. We managed five partial molar pregnancies complicated by severe pregnancy-induced hypertension in the second trimester. We describe the differentiation between complete and partial mole, and the unusual clinical presentation in our patients. PMID- 8515301 TI - Survey of treatment practices for neonatal seizures. AB - A nationwide survey of neonatologists was conducted to determine the common management of neonatal seizures. The questionnaire addressed practice setting, causes, length of treatment, and criteria used in discontinuation of treatment. A response rate of 68% was achieved. Results indicate continued disagreement among practitioners. The prevailing literature recommends treatment of neonatal seizures in the acute phase. Recent studies indicate that 8% to 15% of infants with neonatal seizures will have recurrent seizures after the newborn period. Animal models have shown that brain growth retardation and behavioral and learning impairment may occur from the use of phenobarbital in early infancy. The question of continued treatment of neonatal seizures beyond the acute phase is raised. PMID- 8515302 TI - Myocardial calcification in an extremely low birth weight infant with chronic renal failure and secondary hyperparathyroidism. AB - Myocardial calcification has been rarely described in premature infants after myocardial infarction and myocarditis with coxsackievirus B1. In adults and older children, metastatic myocardial calcification has been reported in chronic renal failure. We report a case of myocardial calcification in a 680-gm preterm infant after a prolonged course of renal failure complicated by secondary hyperparathyroidism. Subclinical myocardial injury was evidenced by a high serum creatine phosphokinase MB band concentration, which probably provided a susceptible substrate for the deposition of calcium crystals, because the multiplication product of serum calcium and inorganic phosphorus levels transiently exceeded 75 mg x mg/100 ml, indicating serum saturation during the course of secondary hyperparathyroidism. We report this case as an unusual complication of renal immaturity in extremely low birth weight infants and an indication of a relatively intact parathyroid glandular function in them. Hypoxia, myocardial dysfunction, and renal failure are common complications in such infants, and in the presence of renal failure, the serum levels of calcium and inorganic phosphorus should be maintained below the pathologic level to avoid ectopic calcification of the tissues, including the myocardium. PMID- 8515303 TI - Umbilical waveform variations in the acutely distressed fetus: an experimental model in the fetal sheep. AB - In previous experimental studies on the pregnant ewe, umbilical arterial and venous waveform variations, produced by maternal aortic and umbilical cord occlusions of different degrees, were investigated in healthy fetuses (pH > 7.30). In our study, the fetal pH in 10 pregnant ewes was first brought down to below 7.20 with a preliminary series of maternal aortic and umbilical cord occlusions; then the 10 ewes were again submitted to a similar series of maternal aortic and umbilical cord occlusion. There were 24 experimental sessions with series of umbilical occlusions and 27 sessions with maternal aorta occlusions. The differences in waveform responses between these two types of fetuses are characteristic. The acidotic fetus produces more protracted drops in S, D, and venous velocity and, at the end of occlusion, the return to normal is slower with no reactive overflow waveform. In addition, there is a typical venous undulating pattern and no reappearance of blood flow velocity during the umbilical cord occlusion (always observed in healthy fetuses). Another important observation is that the fetal heart rate responses (bradycardia or tachycardia or no fetal heart rate variations) are more erratic in the acidotic fetus and do not relate to the intensity of the occlusion or to the fetal pH. The possible clinical implications of these experimental findings are discussed. PMID- 8515304 TI - Association of maternal lithium exposure and premature delivery. AB - Lithium is widely used and the treatment of choice for patients with manic depressive illness. For pregnant patients with manic-depressive illness, however, the use of lithium during the first trimester of pregnancy may present an increased risk for fetal maldevelopment. We have recently cared for several large for-gestational-age, prematurely born infants whose mothers were treated with lithium throughout pregnancy. To determine whether maternal lithium use during pregnancy may predispose to the onset of premature labor and fetal macrosomia, we reviewed records from the International Register of Lithium Babies and from a cohort of manic-depressive pregnant women. More than one third (36%) of infants reported to the International Register were born prematurely, and 37% of the premature infants were large for gestational age; 15% of the term infants were born large for gestational age. In the cohort group, manic-depressive mothers who received lithium during pregnancy had a 2.5-fold higher incidence of premature births than manic-depressive pregnant patients who did not receive lithium treatment. The incidence of large-for-gestational-age births in lithium-treated women in the cohort was not different from that of the general population or from manic-depressive women not treated with lithium. In summary, an association between maternal lithium therapy and premature delivery is reported. We recommend that women receiving lithium therapy during pregnancy be closely monitored for the onset of premature labor. PMID- 8515305 TI - Orogastric tube insertion length in very low birth weight infants. AB - We determined the minimal insertion lengths for appropriate placement of orogastric tubes in very low birth weight infants (< 1500 gm). Feeding tubes marked in centimeter increments were placed orogastrically by using standard neonatal intensive care unit protocol. When radiographs were taken, the centimeter marking at the lip was recorded, and an investigator blinded to the recorded measurement scored the orogastric tube position on radiograph as high (too short), low (too far), or adequate. Data were collected until measurements were available for at least five separate infants for each 250 gm interval of birth weight < 1500 gm. A total of 188 radiographs in 31 consecutive, appropriately grown, very low birth weight infants were reviewed. Seventeen (9%) could not be interpreted because of radiographic technique or because the tip of the orogastric tube was not visible. Of the 171 radiographs suitable for review, the orogastric tube position was low in 8 (5%), high in 57 (33%), and in adequate position in 106 (62%). When data were stratified according to weight groups, minimum insertion lengths were identified, and provided clear and statistically significant separation for orogastric tubes positioned adequately versus those positioned high. The number of orogastric tubes positioned low was too small to provide meaningful information. This information was then used prospectively to assist in orogastric tube(s) position, with a subsequent increase in the percentage of orogastric tubes positioned adequately to 86%. This study confirms that there are minimum orogastric tube insertion lengths required for adequate intragastric positioning. Paying attention to this information can decrease the number of orogastric tubes that are positioned in the esophagus. PMID- 8515306 TI - Back transfer: capability of community hospitals to serve chronically ill and convalescing infants. AB - Severe crowding in neonatal intensive care facilities may prevent many critically ill newborn infants from receiving optimal care. Crowding could be alleviated by back transferring chronically ill or convalescing infants to intermediate-level community hospitals where community-based care can be delivered. The purpose of this study was to assess the ability of such hospitals in North Carolina to care for these children. A telephone survey was administered to all 35 intermediate level community hospitals that had > or = 600 births per year. Hospital resources were assessed on the first call, and a 1-day census was taken for three successive months. Total daily nursery census was 288. Back-transferred infants (32) and infants whose stay exceeded 5 days (32) constituted 24% of the nursery population. Each hospital had a pediatric medical director and necessary equipment to care for back transfers, and 80% of the hospitals could accept a back-transferred infant who was in a neonatal incubator, tube fed, receiving oxygen, 1400 gm, with mild and infrequent apnea and bradycardia--a common clinical picture in such infants. The most severe limitation to accepting infants for back transfer was the shortage of nursing staff appropriately trained to care for this population. These data have implications for effective discharge planning and the development of appropriate community-based, service-delivery systems. PMID- 8515307 TI - Economic consequences of surfactant therapy. PMID- 8515308 TI - Influencing policy on diapering: not for babies only. AB - Recently, nurses and health professionals have been recognized as advocates on the health and environmental issues related to disposable diaper use. In this article, the history of an education project on diapering alternatives and the processes used to affect policy proactively are reviewed. Lessons from this effort to influence institutional and environmental policy are useful as health care professionals become increasingly involved in policy decisions in community and work settings. PMID- 8515309 TI - Neonatologists and bioethics after Baby Doe. AB - The use of hospital ethics committees or infant care review committees has been recommended for difficult decision making. In a survey of military and civilian neonatologists, ethics committees had been established in 27 of their 28 hospitals and fewer than 50% had infant care review committees. Despite the frequently of potential cases for committee review, they were seldom consulted. Inquiry into the educational background of respondents revealed that at least 62% of neonatologists had received ethics education during their professional careers. Most made difficult decisions in conjunction with parents or used a multidisciplinary patient care conference. The use of these conferences antedated any federal regulations. Sixty-seven percent indicated that the Baby Doe regulations had affected neither their thinking about ethical issues nor their practice. In 13 different hypothetical cases in delivery room, intensive care nursery, and long-term care settings, the provision of comfort care, limited care, or withdrawal of support was noted by a sizable percentage of neonatologists; exceptions included meningomyelocele and trisomy 21. The need for ethics committee input in decision making for neonates is questionable. PMID- 8515310 TI - Fetal surveillance during labor: the role of the expert witness. PMID- 8515311 TI - Central venous catheters in low birth weight infants: incidence of related complications. AB - To test the hypothesis that the incidence of central venous catheter-related complications is increased in very low (< 1000 gm) and low (1001 to 1500 gm) birth weight infants compared with larger infants, we retrospectively analyzed the charts of 51 infants with gestational ages 24 to 42 weeks, weighing 0.43 to 12.2 kg at catheter insertion, who had 69 catheters placed at 1 week to 11 months of age between January 1986 and June 1989 at our hospitals. The incidence of infectious and mechanical complications and the frequency of total and infection related complications were significantly greater for infants weighing < 1000 gm at catheter insertion (p < 0.05). Oxacillin-resistant coagulase-negative Staphylococcus organisms accounted for 14 of the 17 episodes of catheter-related septicemia (82%). Six of these episodes were initially treated with antibiotics but without catheter removal; none resolved with catheter salvage. Central venous catheters in very low and low birth weight infants had an 85% and 64% incidence of associated complications, respectively, and should be used with caution in these patients. PMID- 8515312 TI - Genital prolapse in a preterm female infant. AB - Genital prolapse in the female infant during the neonatal period is relatively rare and is usually associated with anomalies of the central nervous system. A case of vaginal prolapse in a small-for-gestational-age preterm female infant, without any associated nervous system anomalies, is presented. The clinical presentation, diagnostic approach, management, and outcome of the case are discussed with reference to a review of the literature. PMID- 8515313 TI - Perinatal pathology casebook. Thanatophoric dysplasia with cloverleaf skull. PMID- 8515314 TI - Ventilatory management casebook. Error in blood gas sampling resulting in a spurious interpretation of compensated metabolic acidosis. PMID- 8515315 TI - Health care reform and access. PMID- 8515316 TI - Decreased fetal movement with abnormal nonstress test preceding fetal death. PMID- 8515317 TI - Should there be mandatory human immunodeficiency virus testing for pregnant women? PMID- 8515318 TI - An experimental model for carpal tunnel syndrome. PMID- 8515319 TI - Treatment of inhalational exposure to hydrofluoric acid with nebulized calcium gluconate. PMID- 8515320 TI - Epidemiologists in industry. Past achievements, unexplored opportunities, and future needs. AB - Epidemiologists in industry have achieved much in the past several years. In addition to conducting important research into known or suspected hazards in the workplace, they have taken the lead in developing a code of ethics for epidemiologists in industry, established guidelines for good epidemiology practices, and have been actively involved in the development of government regulations and the setting of standards. Yet the scope of their activities can be expanded even further. I have discussed some of these, such as environmental health studies, long-term evaluations of health promotion programs, and research into major chronic diseases. But to move into new areas of research and to continue their work in traditional areas, they need to overcome some important obstacles. Among these that I have discussed are: problems involved in getting comprehensive morbidity information into their data bases, restrictions imposed on access to data by privacy protection laws and regulations, and difficulties in publishing and disseminating the results of negative studies. To overcome these obstacles and to enable industry epidemiologists to expand their activities into new areas, they will need additional support from government regulators to ease restrictions on data acquisition, and from company management to provide their epidemiologists with the resources they need. I hope that such support will be forthcoming so that epidemiologic research in industry can achieve its full potential. PMID- 8515321 TI - Factors associated with dysmenorrhea among workers in French poultry slaughterhouses and canneries. AB - The food and agriculture industry employs 15% of the female industrial work force in France. Workers in this industry are exposed to a variety of environmental and organizational constraints: cold, uncomfortable postures, assembly-line work, irregular schedules. In 1987 to 1988, a medical examination and questionnaire were administered to 726 menstruating women who had not been pregnant during the 2 previous years, as part of a study of French workers in 17 poultry slaughterhouses and 6 canning factories. Dysmenorrhea during the previous year was more prevalent among younger women and smokers, and less prevalent among users of oral contraceptives. After adjustment for nonoccupational variables, dysmenorrhea was significantly related to several parameters expressing cold exposure and physical work load. Other parameters such as job satisfaction and hours of domestic work were not associated with dysmenorrhea. PMID- 8515322 TI - The mortality of US nuclear submariners, 1969-1982. AB - A mortality study of 76,160 men who served on US nuclear submarines is reported. Indirect standardization was used to compare mortality rates to those of the US male population. Multiplicative models were developed to explore patterns of mortality within the cohort. Mortality rates for leukemia, acute myocardial infarction, and for motor vehicle accidents were equivalent to those of US males; rates for other causes were lower, generally consistent with the "healthy worker effect." Motor vehicle accident mortality dropped during the study period, perhaps reflecting efforts to control the problem. Suicide rates were depressed during the period of active duty. There was a suggestion that cancer mortality was associated with submarine type; however, the age distribution casts doubt that the excess was occupationally induced. PMID- 8515323 TI - Work-site physical fitness programs. Comparing the impact of different program designs on cardiovascular risks. AB - The relative impact of three different approaches to physical fitness at the work site on cardiovascular risk reduction is examined, based on before/after health screening of employees, and employees' reports of participation in physical exercise activities. The three approaches tested were: 1) a staffed physical fitness facility, 2) one-to-one counseling with at-risk employees, and 3) a combination of one-to-one counseling with employees plus organization of the work site to encourage peer support and mutual exercise activity at work. A fourth site is used as a control site. The program that was centered around a physical fitness facility had little measurable impact on cardiovascular risks, and showed results similar to those at the control site. Both of the other programs were more effective, with the combination of counseling and plant organization providing the best health outcomes in terms of frequency of exercise, adequacy of blood pressure control (among hypertensives), weight loss (among the overweight), and smoking cessation. These results indicate that systematic, ongoing outreach to enlist employees in various types of exercise programs is more effective than the presence of fitness facilities without such outreach. Moreover, significant increases in frequency of exercise can be sustained without a substantial investment in facilities. PMID- 8515324 TI - Injuries to workers in a swine confinement facility. AB - Animal confinement facilities are used to increase efficiency by capitalizing from economy of scale. Investigations of the major health effects of these facilities usually focus on the respiratory symptoms of their workers. We hypothesized that injury may also be a significant health issue for workers. We studied the incidence and patterns of injury during a 3-year period in a large, midwestern swine confinement facility. PMID- 8515325 TI - Soft-tissue injuries related to use of the computer keyboard. A clinical study of 53 severely injured persons. AB - We studied 53 disabled keyboard operators who complained of pain in the forearms, elbows, wrists, shoulders, and hands. Passive wrist flexion and dorsiflexion impairment to less than 70 degrees due to myofascial shortening associated with an increase in forearm muscle pain on palpation was a useful clinical indicator of injury. Isometric muscle testing was useful in detecting injury to specific muscles. Ligamentous hypermobility of finger joints (72%) and harmful inefficient keyboard styles (intrinsic ergonomic factors) were noted, videotaped, and analyzed. Changes in the workstation (extrinsic ergonomic factors) alone may not be adequate treatment. Individual intrinsic ergonomic factors must also be recognized, addressed, and corrected by a combination of physical therapy, conditioning, technique retraining, education, and counseling. A taxonomy of keyboard technique is proposed as an aid to recognizing potentially harmful postures. PMID- 8515326 TI - A nurse practitioner intervention to increase breast and cervical cancer screening for poor, elderly black women. The Harlem Study Team. AB - OBJECTIVE: To compare nurse practitioner (NP) and physician rates of breast and cervical cancer screening among poor, elderly black women. DESIGN: A quasi experimental design was used to compare pre- and postintervention annual screening rates. Rates were determined by medical record audits. SETTING: Two urban public hospital primary care clinics served as the study sites. PATIENTS: All women aged 65 years or more were eligible to participate. INTERVENTIONS: Women were offered screening by a NP during a routine visit in the intervention site; a physician reminder system was used in the control site. MAIN RESULTS: Baseline annual screening rates were comparable in the two study sites. At the end of the study period, rates were significantly higher in the NP site, compared with the control. In the NP clinic, the annual rate of Pap tests increased to 56.9% from the baseline of 17.8%, and mammographies increased to 40% from 18.3%. In comparison, rates remained low in the control site, increasing only to 18.2% of women receiving Pap tests from a baseline of 11.8%, and remaining at 18% for mammography. CONCLUSIONS: Use of a NP to deliver same-day screening is an effective strategy to target poor, elderly black women for breast and cervical cancer screening. However, even with the substantial increases in rates obtained with the NP intervention, screening in this vulnerable population remains below nationally targeted levels. PMID- 8515327 TI - Changes in the pattern of drug overdoses. AB - OBJECTIVE: To describe changes in the pattern of patients with drug overdoses hospitalized over the past two decades. DESIGN: Retrospective data review. SETTING: A 719-bed university-affiliated hospital. PATIENTS: All adults admitted to the hospital with drug overdoses in 1968, 1979, and 1989. PRIMARY OUTCOME MEASURES: Changes in demographics, drugs used, and discharge disposition. RESULTS: A majority of patients admitted with drug overdoses have had previous suicide attempts; and while women predominate, they make up a decreasing proportion of admissions over time (76% in 1968 to 52% in 1989 (p = 0.003). Benzodiazepines were the drugs most commonly used in 1979 and 1989, and cocaine has shown a marked increase in use over time, while barbiturate overdoses have progressively decreased. The use of two or more drugs is common and has been consistent over time, as has been the concomitant use of alcohol. The mortality rate has remained low at 1%, but mean length of stay has decreased dramatically from 6.6 days in 1979 to 3.2 days in 1989 (p < 0.001) and discharge disposition has shifted from out-patient to inpatient psychiatric care. CONCLUSIONS: The majority of patients admitted to a general acute care hospital following a drug overdose have a history of previous suicide attempts and are followed by a mental health professional. The changing pattern of drugs used over two decades reflects trends in drugs used in the community in general and by patients with mental illness in particular. Discharge disposition has changed over time and is related to patients' insurance status. PMID- 8515328 TI - What do senior internal medicine residents do in their continuity clinics? AB - OBJECTIVE: To describe the activities of second- and third-year internal medicine residents during their outpatient continuity clinics. DESIGN: Descriptive observational study. SETTING: Medical school-affiliated community hospital primary care clinic. PATIENTS/PARTICIPANTS: All second-year (n = 15) and third year (n = 14) residents enrolled in the internal medicine training program were observed at one-minute intervals during their routine half-day continuity clinics. MEASUREMENTS AND MAIN RESULTS: An average of 203 observations were recorded for each resident. The distribution of resident activities was as follows: 1) direct interaction with patients (29.5%); 2) charting or writing prescriptions (24.0%); 3) social interactions with staff (13.7%); 4) attending conferences or reviewing medical literature (9.4%); 5) waiting or transiting (8.2%); 6) ward responsibilities (4.9%); 7) reviewing cases with attending physicians (4.4%); and 8) miscellaneous activities (4.9%). Analysis of variance procedures revealed that the following variables significantly (p < 0.05) affected the residents' activities: 1) the actual number of patients seen produced predictable increases in direct and indirect patient care activities; and 2) the year of training had an impact on the mean number of observations of interactions with the supervising attending physician (PGY-2 = 11.4, PGY-3 = 3.8). CONCLUSIONS: These results suggest that this senior resident continuity experience is clinically intensive, yet provides surprisingly infrequent direct resident supervision. Further analysis of the educational activities occurring on these half-days is necessary to judge whether they are quantitatively and qualitatively adequate. PMID- 8515329 TI - Learning outcomes of an ambulatory care rotation in internal medicine for junior medical students. AB - OBJECTIVE: To assess the educational outcomes of training junior medical students in an eight-week combined ambulatory/inpatient rotation compared with those of training exclusively on inpatient services. DESIGN: Participants were randomly assigned to one of three groups: those who volunteered for the ambulatory/inpatient rotation and were randomly selected; those who volunteered and were not selected; and those who did not volunteer. SETTING: University-based internal medicine (IM) inpatient services and community-based clinics and private practices. PARTICIPANTS: Seventy-five third-year medical students taking the required eight-week IM clerkship. INTERVENTION: Assessment included both pre- and posttest measurement of students' knowledge of general internal medicine and a profile of the types of patients problems seen by students in ambulatory settings. RESULTS: While students' general medicine knowledge scores increased significantly from pre- to posttest (p < 0.001), there was no significant difference in scores between the ambulatory/inpatient and exclusive inpatient groups. Patient log data indicated notable differences in the diagnostic compositions of students' patient loads. For instance, 38% of the ambulatory diagnoses were infectious disease, neurologic, endocrine, rheumatologic, or dermatologic problems, and another 15% were non-IM (e.g., obstetric/gynecologic; ear, eye, nose, and throat) problems. Only 24% of the inpatient diagnoses reflected these specialty areas. CONCLUSIONS: Ambulatory training did not significantly affect students' knowledge gain compared with that for exclusive inpatient training, but student evaluations of the rotation plus patient log data suggested that ambulatory training can provide a more complete view of general medicine practice than can exclusive inpatient training. PMID- 8515330 TI - Evaluation of resident performance in an outpatient internal medicine clinic using standardized patients. AB - OBJECTIVE: To observe and evaluate the performance of primary care internal medicine residents within the outpatient clinic milieu. DESIGN: Longitudinal descriptive study. PATIENTS/PARTICIPANTS: 48 internal medicine resident encounters with two standardized patients at the University of Wisconsin General Internal Medicine Clinics. INTERVENTION: Residents were rated by the standardized patients with a medical skills checklist and an interpersonal skills checklist, and by the staffing physician with a clinical reasoning skills checklist. The investigators reviewed audiotapes of the standardized patient encounters for strategic management skills. MAIN RESULTS: Resident performance on these scales was examined for improvement with years of training; when considered separately, no such effect was seen for either standardized patient case. When the cases were grouped together, however, there was significant improvement on the Clinical Reasoning Instrument. The grouped standardized patient data were compared with data from inpatient faculty evaluations of the residents. Faculty evaluations correlated with standardized patient evaluations of resident performance only on the medical checklist. Finally, comparison of the four assessment scales demonstrated a significant correlation between interpersonal skills, as assessed by the patient, and strategic management skills. CONCLUSION: Resident outpatient performance, measured in a blinded setting, does not improve with year of training. Faculty inpatient assessments of residents correlate with medical "thoroughness" as measured by a medical skills checklist, and interpersonal skills as rated by standardized patients correlate with resident use of strategic medical management. PMID- 8515332 TI - Involving patients in complex decisions about their care: an approach using the analytic hierarchy process. PMID- 8515331 TI - Survivors of motor vehicle trauma: an analysis of seat belt use and health care utilization. AB - OBJECTIVE: To determine whether the protective effects of seat belt use on acute injury are followed by corresponding reductions in outpatient health care utilization. DESIGN: Retrospective cohort analysis. SETTING: Northern California Region Kaiser Health Plan hospitals and medical offices. PATIENTS: All Kaiser Foundation Health Plan members injured in motor vehicle crashes in Santa Clara County during one year (total number of patients = 246). MEASUREMENTS AND MAIN RESULTS: 54% of the study participants had been wearing seat belts at the time of injury, and 46% had not been. The belted patients had fewer head injuries (30% vs 50%, p < 0.05), better mean Injury Severity Scale scores (4.3 vs 7.4, p < 0.05), and smaller mean hospital charges ($8,580 vs $16,209, p < 0.05). However, the effects of injury did not end upon discharge from the trauma center; the patients averaged about eight outpatient visits during the subsequent year, a rate almost double their prior use. In contrast to inpatient measures of utilization, the patients who had been wearing seat belts at the time of injury had more outpatient visits during the year after injury than had their unbelted counterparts (9.0 vs 7.1, p < 0.05). This discrepancy was not explained by differences in amounts of utilization during the year before injury, which were similar in the two groups (4.4 vs 4.8, p = NS). Overall, general internists provided the most follow-up care and accounted for the largest discrepancy in utilization between the belted and unbelted patients. CONCLUSIONS: Seat belt use does not result in lower utilization of follow-up outpatient services in the year following injury. However, the beneficial effects on acute care utilization more than offset the marginal effects on subsequent medical services utilization. PMID- 8515333 TI - Rural HIV infection: the window of opportunity for action is still wide open. PMID- 8515334 TI - Accepting death without artificial nutrition or hydration. PMID- 8515335 TI - Forgoing medical nutrition and hydration: an area for fine-tuning clinical skills. PMID- 8515336 TI - A comparison of costs, labor time, and needle use associated with single- and multi-line intravenous infusion systems. AB - This study compared the use of single and multiline infusion systems on a general surgical unit. When the multiline infusion system was used, less nursing time was required and fewer needles were used. Equipment costs were higher but these costs were offset by savings in labor costs. PMID- 8515337 TI - Methods for determining the internal volume of central venous catheters. AB - A prevalent problem associated with central venous catheters (CVCs) is occlusion with clotted blood or drug precipitate. When an occlusion occurs, the inability to determine a CVC's internal volume may seriously delay instillation of a precise quantity of a corrective drug. A lack of standards for CVC measurements and confusion about terminology for describing catheter geometry are partly to blame. This article aims to alleviate the problem, providing three methods for determining CVC internal volume with two reference tables and mathematical support for all calculations. A glossary of CVC terms is also included. PMID- 8515338 TI - Integrating the licensed practical nurse and the licensed vocational nurse into the specialty of intravenous nursing. AB - In the scope of intravenous nursing practice, Licensed Practical Nurses (LPNs) and Licensed Vocational Nurses (LVNs) can competently perform specific IV therapy procedures after successfully completing a well-structured IV nursing continuing education process. This article provides an overview of the various processes that need to be employed to ensure IV nursing competency of LPNs and LVNs before effectively integrating them into the specialty of IV nursing. PMID- 8515339 TI - Central venous access devices: current technologies, uses, and management strategies. AB - The use of central venous catheters (CVCs) for vascular access is now commonplace in a variety of care settings. Technological advances related to CVCs have introduced a multitude of catheter designs that are available to us through numerous manufacturers. To initiate the appropriate procedures for care, nurses involved in the maintenance of central venous access devices are now challenged with having to be familiar with a large variety of central venous access devices. They must be able to evaluate a CVC and determine its type, size, manufacturer, and specific characteristics as well as to initiate the appropriate management strategies related to that device. The nurse must also be able to recognize the indications, advantages and disadvantages associated with each device, and to assist the patient in making an informed decision regarding the appropriate device for his or her therapy needs. It is essential that care and maintenance procedures be delivered by those whose knowledge base and experience make them competent care providers with the expertise to initiate appropriate prevention and troubleshooting measures, as well as to evaluate and implement nursing actions related to complications. PMID- 8515340 TI - Home infusion of intravenous immune globulin in human immunodeficiency virus- infected children. PMID- 8515341 TI - Restoring patency of long-term central venous access devices. PMID- 8515342 TI - Solubilities of trimethoprim and sulfamethoxazole. PMID- 8515343 TI - Use of microcolonies. PMID- 8515344 TI - Scale-up of immediate release oral solid dosage forms. AAPS/FDA Workshop Committee Report. PMID- 8515345 TI - FDA's aseptic processing: proposed regulation. PMID- 8515346 TI - Interaction between air movements and the dispersion of contaminants: clean zones with unidirectional air flow. AB - The purpose of this presentation is to describe the theoretical relations for the dispersal of airborne contaminants and to illustrate the validity of these equations occurring during factual situations, where a number of observations on air movements in open unidirectional air flow units supplied with HEPA-filters are described. In factual situations the aerodynamic system which governs the dispersion of contaminants in reality is always very complicated that risk situations must be mapped and assessed empirically. The presence of a person can give risk to wakes that may be stable or unstable. The unstable situations are in most cases caused by the influence of arms and hands. As part of the microbiological assessment of aseptic processes carried out in clean zones, it is important to investigate that such vortices do not occur in the clean working areas. As the level of airborne contaminants in the operational environment may have an effect on the level of product contamination, the microbiological assessment of aseptic processes is important. A system is described for microbiological assessment in unidirectional air flow units by using visual illustrative methods and particle challenge tests (measured by particle counter) for the dispersion and/or induction of particles. PMID- 8515347 TI - Monitor lyophilization with mass spectrometer gas analysis. AB - This paper presents a brief review of the basic issues of lyophilization and the fundamentals of quadrupole mass spectrometry. The emphasis of the paper is on the application of a quadrupole mass spectrometer as a process monitor. The details of sampling and data collection are discussed. Data taken while monitoring lyophilization is presented in conjunction with cycle optimization, end point detection and contaminant detection. PMID- 8515348 TI - Freeze-thaw studies of a model protein, lactate dehydrogenase, in the presence of cryoprotectants. AB - The objective of this study was to investigate the behavior of lactate dehydrogenase (LDH) upon freezing and thawing, alone or in the presence of several selected cryoprotectants. Also, the influence of the freezing rate on retainment of LDH activity was investigated. It was observed that fast freezing caused less loss of LDH activity than slow freezing. The probable mechanisms of loss of activity after freeze-thaw cycles were discussed. Selected cryoprotectants were evaluated for their ability to protect LDH during freeze thaw cycles. Surface tension and pH change measurements upon freezing of the cryoprotectant solutions were carried out. Based on the results of these experiments, a potential mechanism of cryoprotection has been developed. PMID- 8515349 TI - Validation master planning. PMID- 8515350 TI - Ten steps to ensure a successful preNDA approval inspection. AB - To say that the FDA preapproval inspection program has generated much interest is an understatement. There have been multiple Commissioner Exchange Meetings at various locations throughout the United States and several multi-day workshops sponsored by the industry to help clarify how to prepare for this inspection. In order to establish a baseline of understanding, we will look, briefly, at the agency expectations. We will then look at the general trends that we have observed either directly from the preapproval inspections we have experienced or indirectly from 483 observations from other preapproval inspections. Finally, the ten steps which are used at Eli Lilly and Company to prepare for preapproval inspections will be presented. PMID- 8515351 TI - Total quality in tubing glass manufacturing. AB - Today's demand for higher quality products can be satisfied through a comprehensive quality assurance system (Total Quality System, "Worldwide Quality Standard") using the latest state of the art measuring technologies. Totally automated state of the art glass vial manufacturing begins once the glass tubes are loaded into the machine and ends with the finished product in the packaging machine, all without human contact. This standard is achieved by measuring dimensions with SPC (statistical process control) and 100% inspection of the products. These systems complement each other and give the machine operator instant data in an overview format. To achieve the visual requirements forma vitrum developed the FVC90 control line. This optical surface inspection device controls online and without contact 100% of the products for cosmetic defects as small as 50 microns. It can detect and eject defects such as dirt, scratches, chips, air-lines, loose glass particles, cracks, etc. The sensitivity of the system can be adjusted and is fixed based on client needs. An important quality assurance technique is the checking of dimensions at the production machine with a Vision System. With this system deviations are instantly recognized and corrections can be made immediately, thus assuring that glass products can be run on the high-speed filling machines for which they are designed. These computer assisted inspection systems are key in producing the highest quality pharmaceutical glassware in the 90's. PMID- 8515352 TI - Current practices in the validation of aseptic processing--1992. PMID- 8515353 TI - Clinical significance of fetal heart rate patterns during labor. IX: Prolonged pregnancy. AB - The intrapartum FHR and UC were recorded in a population of 707 consecutive cases of prolonged gestation looking for a characteristic pattern. There is no typical pattern for prolonged pregnancy. However, there are differences from preterm and term populations. There is a very high incidence of variable (55%) and late (17%) decelerations. These were seen more frequently among cases receiving oxytocin. Nearly 50% of C-sections had lates. Baseline alterations (tachycardia 26%, fixed 8%, and saltatory 17%) were often associated. Apgar scores < or = 6 at 1 minute were correlated with variable and late decelerations. However, acidemia (UA pH < or = 7.20) could not be predicted from FHR patterns because there was no correlation between low pH and clinical depression. Alarmingly a few fetuses in agonal state presented normal appearing tracings, or deteriorated rapidly without the usual indicative changes by FHR. All intrapartum or NND had this misleading pattern. In view of this unpredictable aberrant pattern as the only certain means to prevent these deaths, it is suggested that no pregnancy should be allowed to reach 294 days post LMP. PMID- 8515354 TI - A simplified preinduction scoring method for the prediction of successful vaginal delivery based on multivariate analysis of pelvic and other obstetrical factors. AB - Most of the popular preinduction scoring methods were created three decades ago, applied to selected populations and based on analysis of each factor separately. In order to overcome these limitations and to try and create a simple and reliable scoring method, 401 inductions of labor were analyzed. Failure was defined as delivery by cesarean section, regardless the indication. Results of multivariate analysis demonstrated that only two of the five factors used by Bishop's method were included (cervical dilatation and fetal head station). Gestational age and parity also constituted important factors and thus the new method incorporates these four factors. The variables among each factor were scored according to their relative risk, obtained from the analysis; dilatation 3 cm or more = 2, dilatation 1-2 cm = 1, fetal head station -1 cm or lower = 1, multiparity = 1, term delivery = 1, closed cervix = 0, station -2 cm or higher = 0, primiparity = 0 and non-term delivery = 0. Comparison of the suggested scoring method and Bishop's method demonstrated that in the low score category our method predicted more accurately cesarean section rate (44.7% and 27.6%, respectively). No difference was noted among the middle or high score groups. More studies among other populations may clarify whether our proposed method really overcomes other methods concerning simplicity, universality and predictability. PMID- 8515355 TI - Therapeutic exercise for insulin-requiring gestational diabetics: effects on the fetus--results of a randomized prospective longitudinal study. AB - Regular physical activity is an established therapeutic adjunct in diabetes, but has not been offered to pregnant diabetics in the past; for sports might induce significant cardiovascular and hormonal changes that are able to reduce blood flow to the uterus and thus limit oxygen transfer to the fetus. Studying the impact of a medically supervised exercise program on gestational diabetes mellitus [GDM) in a randomised prospective longitudinal study, this paper aims to assess the effects of maternal moderate and strenuous exercise on the fetus. By evaluating shortterm fetal responses as reflected in heart rate patterns (FHR) and longterm-pregnancy complications and neonatal outcome, our results suggest that--in absence of ominous FHR changes or significant changes in uterine activity following the exercise sessions or increased diabetes-related peri- and neonatal morbidity--regular physical activity seems to be a safe therapeutic option for the fetus of GDM mothers. PMID- 8515356 TI - Nuchal-fold thickening in Down syndrome fetuses: transient appearance and spontaneous resolution in the second trimester. AB - To elucidate the cause of the wide variation of sensitivity of the nuchal-fold thickness (NFT) for a noninvasive prenatal screening test for fetal Down syndrome, we consecutively measured the NFT throughout pregnancy in eight fetuses with Down syndrome and 100 normal fetuses (negative controls) using video recorded ultrasonography. When 6 mm was set as the cutoff value, 6/8 Down syndrome fetuses showed a NFT above this value at least once during pregnancy. However, the thickening was transient in 5 of them and resolved spontaneously during the second trimester. Persistent thickening of nuchal-fold was only observed in one fetus. From the results of the present study, we recommend that the NFT be measured repetitively during the first and second trimesters as a noninvasive prenatal screening test for Down syndrome. PMID- 8515357 TI - Vitamin A levels at birth of high risk preterm infants. AB - Vitamin A levels were measured shortly after birth in preterm infants at high risk of developing chronic lung disease (CLD). Eleven infants, median gestational age 24 weeks, developed CLD. Their results were compared to 11 infants who, although they required mechanical ventilation for at least 48 hours, did not develop CLD. The median gestational age of this latter group was 30 weeks (range 27-35). The median vitamin A level of the infants who developed CLD was 0.62 umol/l (range 0.41-0.95), which was significantly higher than the median level of the infants who did not develop CLD, which was 0.36 umol/l (range 0.13-0.89). We conclude preterm infants who develop CLD are not predisposed to develop that complication by low vitamin A levels at birth. PMID- 8515358 TI - Post-mortem concentrations of hypoxanthine in the vitreous humor--a comparison between babies with severe respiratory failure, congenital abnormalities of the heart, and victims of sudden infant death syndrome. AB - Post-mortem hypoxanthine concentrations in the vitreous humor of human infants were investigated. Hypoxanthine is formed from hypoxic degradation of adenosine monophosphate. The concentrations in the vitreous humor can give information about antemortem hypoxia. The post-mortem levels were corrected for the time elapsing between death and the autopsy. Four groups of infants were compared: 17 babies who died of respiratory distress syndrome (RDS), 72 infants who died of sudden infant death syndrome (SIDS), 23 children dying of congenital heart disease (both cyanotic and acyanotic), and 15 children dying acutely in accidents without any known significant time of hypoxia before death. The corrected, median hypoxanthine levels in victims of SIDS (200 mumol/L) was significantly higher (p < 0.01) than in the accident group (0 mumol/L), but no clear difference was found between the SIDS group and the RDS group (101 mumol/L), or the heart group (54 mumol/L). A number of children with "normal" hypoxanthine levels (0 to 38 mumol/L) were found in all four groups, but the numbers were significantly lower (p < 0.005) in the RDS, SIDS and heart groups than in the accident group. It is concluded that SIDS is probably not a sudden event, but may be preceded by relatively long, or repeated intermittent periods of hypoxia (of unknown etiology). PMID- 8515360 TI - Atrial natriuretic factor in neonatal hypoxic-ischemic encephalopathy. AB - The influence of perinatal asphyxia in the secretion of atrial natriuretic factor (ANF) during the first 6 days of life, and its renal consequences are discussed. Comparison between 20 healthy term neonates and 19 with first--or second--degree hypoxic-ischemic encephalopathy (HIE) is made. Daily controls were performed on clinical and neurological examinations and administration of sodium and fluids. On the first and sixth days of life, 24 hours urine collection, natremia, natriuresis, fractionated excretion of sodium and creatinine clearance were determined. The ANF was performed at 1, 2, 3 and 6 days old, by R.I.A. The full term newborns with HIE showed a peak in ANF values on day two, as does the control group, thereafter maintaining higher levels, with a significant difference on day three and six. No correlation could be found between the ANF levels and the renal variables analyzed. PMID- 8515359 TI - Ultrasonic and magnetic resonance imaging diagnosis of placenta accreta managed conservatively. AB - Placenta accreta, a rare but life-threatening complication of pregnancy, is generally treated by hysterectomy and is histologically proven. We report a case that was managed conservatively and the diagnosis was confirmed by ultrasound and magnetic resonance imaging. PMID- 8515361 TI - Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in patients with juvenile, rapidly progressive, and adult periodontitis. AB - The aim of this study was to compare hydroxyproline (Hyp) and total protein levels both in the gingiva and gingival crevicular fluid (GCF) from juvenile (JP), rapidly progressive (RPP), and adult periodontitis (AP) patients and periodontally healthy controls (C). A total of 60 individuals, 15 from each group, were studied. GCF was obtained before gingival sampling. Clinical measurements were recorded. The gingival samples were harvested by full thickness flap operation from patients and immediately after the extraction of the teeth for orthodontic reasons from controls. The samples were analyzed biochemically. GCF Hyp levels were significantly higher in the AP group than those of the RPP and C groups. The strong positive correlations between gingival and GCF Hyp levels were determined in the disease groups. Total protein levels in both the gingiva and GCF were significantly higher in disease groups. However, the differences between the disease groups were not statistically significant. Correlations between the clinical parameters and Hyp levels in gingiva and GCF were determined. The findings indicate the Hyp and total protein levels both in the gingiva and GCF appeared to be increased in the disease groups. These findings suggest that both the synthesis and degradation of collagen and total protein are elevated in periodontal disease. However, our findings do not support the concept that measurement of either Hyp or total protein levels in gingiva or GCF is a suitable or reliable criterion in determination of disease activity. PMID- 8515362 TI - Oriented cell and fiber attachment systems in vivo. AB - This investigation was undertaken to evaluate whether an oriented cell and fiber attachment system would develop if demineralized dentin surfaces were approximated in vivo. The approximated surfaces consisted of the internal, parallel surfaces of dentin cylinders. The experimental group was demineralized on both the external and internal surfaces of the dentin cylinder with citric acid, pH 1.0, for 3 minutes, but only the external surface of the control dentin cylinder was demineralized. Specimens were implanted transcutaneously into the backs of rats with one end protruding through the surface of the skin. Three specimens in each group were available for analysis at 1 and 10 days after implantation. The groups were compared using histologic and histometric analysis and the following conclusions were made. There were marked differences in the initial cellular response between the groups, and demineralization with citric acid prior to implantation predisposed towards a greater cell attachment at 1 and 10 days. An oriented fiber attachment developed between the demineralized approximated surfaces by 10 days, but did not develop between nondemineralized approximated surfaces. The morphology of the fiber attachment system was structurally similar to a periodontal ligament, with inserting fibers perpendicular to the implant surface. The findings of this study suggest that spatial approximation of appropriate substrates facilitates development of cell and fiber orientation. Thus, to regenerate a functionally oriented attachment system in the clinical setting, it may be beneficial to provide substrates that are appropriately approximated. PMID- 8515363 TI - Histologic and histometric responses to polymeric composite grafts. AB - The present study was designed to determine whether a polymeric composite promotes new attachment in artificially-induced bony defects in the dog model. HTR, hard tissue replacement, is a non-resorbable calcium-layered polymer of polymethyl-methacrylate and hydroxyethyl-methacrylate. It has been reported to be clinically non-inflammatory, osteophilic, and osteoconductive. For the study, 4 beagle dogs, 4 to 6 years old with no periodontal disease were used. Mucoperiosteal flaps were raised including the 2nd, 3rd, and 4th maxillary premolars. Buccal Class II furcation defects were created on these premolars. Reference notches were placed in the roots at the level of the bony defects. Test quadrants were selected by the toss of a coin, and furcations were filled with the polymeric composite particles wetted with sterile saline. Following grafting, the flaps were approximated and sutured. The contralateral side, serving as control, was treated by flap debridement only. Sutures were removed 7 days after surgery. Dogs were sacrificed 4 months following surgery. Mesio-distal histological sections were evaluated by descriptive histology. In addition, surface area determinations (in mm2) of the furcal tissues were carried out using the microscope attached to a digitizer and a computer. In 8 mesio-distal serial sections cut 30 microns apart in both experimental and control teeth, surface area determinations relative to the furcations were made evaluating: 1) the total fill of the furcation; 2) the area filled with alveolar bone; 3) the area occupied by connective tissue; 4) the area occupied by new deposited cementum; and 5) the area filled by epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515364 TI - In vivo scaling and root planing forces in molars. AB - The purpose of the present study was to assess in vivo scaling and root planing forces in molars of periodontitis patients. Ten dentists and 10 dental hygienists scaled and root planed the mesial and distal aspect of one first molar, using Gracey curets 11/12 and 13/14. Scaling and root planing forces were recorded using a piezo-electric receiver, an electronic transducer, and an analogous writer. The forces were recorded in mV and converted into Newtons (N). Three different types of forces were recorded: positive forces during working strokes and positive and negative forces during preparation of working strokes. Multivariate repeated measures analysis of variance was used to assess differences in force between curet types. The mean positive scaling forces exerted with curet 11/12 were statistically significantly (P = 0.0005) greater than the corresponding forces exerted with curet 13/14 in all therapists. The mean positive root planing forces applied with the curet 11/12 were significantly (P = 0.0008) greater than the forces exerted with curet 13/14. The mean positive interstroke forces did not differ between curet 11/12 and 13/14. The mean negative interstroke forces impacting on the soft tissues exerted with curet 11/12 did not significantly differ from curet 13/14 during scaling and during root planing. Therapists differed significantly among themselves for each type of positive and negative force (P < 0.001 in all cases). These results suggest that the extent of instrumentation given to root surfaces in molars depends more on the therapist and on the molar aspect being treated than on the needs of a specific site. PMID- 8515365 TI - The presence of an inhibitor of human skin collagenase in the roots of healthy and periodontally diseased teeth: changes that occur with age. AB - The amount of anti-collagenase in the root has been reported in a group 18 to 35 years of age. Healthy roots had more than the diseased; and apical more than the cervical. The purpose of the present study is to determine the effect of age on these values. In a group 50 to 92 years of age, all values were markedly higher than in the younger group. In addition, all relationships between values were preserved. These include location and presence of disease. The higher levels might be due to an aging process or a protective defense against collagenase in the gingival crevice. PMID- 8515366 TI - Hypersensitive dentin: testing of procedures for mechanical and chemical obliteration of dentinal tubuli. AB - This study examined by scanning electron microscopy the effect of various mechanical and chemical procedures in obliterating dentinal tubuli. Dentin blocks containing open, cross-sectioned dentinal tubuli were separated into one experimental and one control area. The mechanical treatments consisted of 20 seconds of continuous instrumentation with sharp and dull curets, finely textured inserts for the EVA reciprocating handpiece, metal and plastic inserts for a sonic scaler, and metal inserts for an ultrasonic scaler. Chemical treatments included a light-cured dental resin and active obliterating agents including sodium, stannous and hydrogen fluorides, potassium oxalate, glycerin, ferric oxalate, and potassium nitrate. These substances were applied to the test surfaces for 2 minutes and allowed to dry. One half of the chemically treated specimens were then sprayed with water in order to evaluate the retention of the obliterating agents. The results revealed that among the mechanical treatments, the sharp curet gave the most consistent and complete obliteration of the tubuli. The plastic inserts had no tubular occluding effects. Among the chemical procedures, the light-cured resin resulted in the most complete obliteration of the tubuli, while the fluoride agents and glycerin had no effect. It can be hypothesized that combining instrumentation with a sharp curet causing a heavy smear layer and occlusion of tubuli apertures, followed by application of a light body resin, may prove to be a rational method of desensitizing hypersensitive dentin surfaces. However, this combined treatment should be evaluated in clinical trials. PMID- 8515367 TI - A light microscopy, scanning electron microscopy, and laser scanning microscopy analysis of retrieved blade implants after 7 to 20 years of clinical function. A report of 3 cases. AB - The aim of the present study was to evaluate by means of light microscopy, scanning electron microscopy, and laser scanning microscopy the thin ground sections of blade implants retrieved after 7 to 20 years of clinical function. Microscopic examination revealed that most of the implant surface had an intimate contact with compact lamellar bone tissue. Higher magnifications revealed the presence of a gap (1 to 5 mu) interposed between bone and implant. Many osteocytes were near the implant surface and, in many instances, osteocyte canaliculi, running from the lacunae towards the implant surface, were seen. Structures similar to bone reversal lines were observed at the edge of the bone side of the interface. The bone-titanium region is probably an area of dynamic biological activity. PMID- 8515368 TI - A possible late onset variation of Papillon-Lefevre syndrome: report of 3 cases. AB - Three unusual cases of Papillon-Lefevre syndrome with late onset of features and relatively mild periodontal disease are presented. These examples confirm some of the late onset of features and mild periodontal presentation of a previous case report. Bacteriologic associations, polymorphonuclear leukocyte chemotactic, phagocytic, and bactericidal activity, and therapeutics with regard to this syndrome are discussed. PMID- 8515369 TI - Histologic assessment of new attachment following the treatment of a human buccal recession by means of a guided tissue regeneration procedure. AB - A deep, long-standing recession on a mandibular incisor was treated in a 56-year old female patient. The tooth was tilted buccally and was scheduled for extraction. The recession was 8 mm deep, with a pocket depth of 1 mm and no keratinized tissue. The recession was treated by guided tissue regeneration; the membrane was left in place for 4 weeks. The tooth was extracted along with marginal tissues 5 months after the removal of the membrane. At the time of extraction, 4 mm of root coverage had been achieved and 3 mm of keratinized tissue were measured buccally. Histologic measurements showed that 3.66 mm of new connective tissue attachment had been obtained associated with newly formed cementum (2.48 mm) and bone growth (1.84 mm). The crestal bone level after treatment was located coronal to the preoperative location of the gingival margin. PMID- 8515370 TI - Flexor digitorum longus tendon transfer. AB - A retrospective evaluation consisting of a written survey and physical examination was completed on flexor digitorum longus tendon transfer patients. The tendon transfer is used to alleviate symptoms and address imbalance of extrinsic and intrinsic muscles. The authors present an evaluation of 110 procedures with an average follow-up period of 65.7 months (range 7 to 198 months). A literature review, discussion of a new theory as to the etiology of hammer toes, and criteria for using the procedure are included. PMID- 8515371 TI - Etiology of symptomatic recurrent interdigital neuromas. AB - Morton's neuroma is a common disease entity of the foot that is often treated with surgical resection. A complication of neuroma resection is recurrence of symptoms as a result of the formation of an amputation neuroma. The authors offer an anatomical and biomechanical explanation for the location of symptomatic amputation neuromas. The neuromas are found on the plantar surface proximal to the condyles of the metatarsal and medial to the interspace where the nerve is resected. The theory is based on intraoperative observations during surgery for recurrent neuromas and on cadaver dissections and offers a method based on this theory to reduce the number of recurrences. PMID- 8515372 TI - Transverse plantar incision for heel spur surgery. Four-year follow-up survey of 35 patients. AB - A transverse plantar incisional approach was used on 35 patients who underwent heel spur surgery from 1982 through 1990. Ten bilateral procedures were performed on a total of 45 feet. A medial approach was used for five of the bilateral surgeries. The average age of the patient was 47 years, and the average follow-up period was 49 months. Of the 34 plantar approach cases in which complete data were obtained, 94% showed either good or excellent results. The authors illustrate a technique using a transverse plantar incision as an alternative to the medial approach for heel spur surgery. PMID- 8515373 TI - Epiphysiodesis of the first metatarsal with cancellous allograft. AB - The authors describe a technique for an isolated epiphysiodesis of the first metatarsal with a cancellous allograft for the correction of juvenile hallux abducto valgus deformity. The procedure requires no incision. It is a benign, safe, and effective way of correcting the deformity. PMID- 8515374 TI - Generalized granuloma annulare in a diabetic patient. A case report. AB - Granuloma annulare is a rare skin condition sometimes associated with diabetes mellitus. The natural history including diagnosis and therapy are discussed and a case is presented. PMID- 8515375 TI - Rheumatoid arthritic foot. Two manifestations with case studies. AB - The authors review rheumatoid arthritis with focus on two pedal manifestations, rheumatoid nodules and digital deformities. The prevalence, presentation, and diagnostic features concerning these entities are discussed, and three case studies are presented. PMID- 8515376 TI - Reflex sympathetic dystrophy syndrome. AB - Reflex sympathetic dystrophy syndrome is a troublesome, complex disorder that presents with chronic, unexplained aching or burning pain, the intensity of which is incommensurable with the original injury. Six diagnostic criteria have been described by Genant et al: pain and tenderness in the extremities; swelling of soft tissue; diminished motor function; trophic skin changes; vasomotor instability; and patchy osteoporosis. Currently, the most widely accepted etiology is an initial vasomotor reflex spasm occurring after an injury to the extremity, followed by a loss of vascular tone, persistent vasodilation, and rapid bone resorption. PMID- 8515377 TI - Foreign bodies in the foot. AB - A symptomatic foreign object lodged in the foot can be a difficult problem. The object's location and shape are the most important factors to identify before removal of the object is attempted. Many different imaging modalities have been used to locate the foreign objects in the foot. The authors briefly reviewed several common imaging modalities. Computed tomography appears to be superior to the other imaging modalities discussed in visualizing and localizing foreign objects in the foot. Magnetic resonance scanning is probably equal to computed tomography but is less readily available and more expensive and is contraindicated with ferrous metal foreign bodies. PMID- 8515378 TI - Intraosseous lipoma of the os calcis. AB - The authors present three cases of a rare calcaneal tumor, intraosseous lipoma. The differentiation of intraosseous lipoma from other benign tumors is discussed. The diagnosis and treatment are reviewed. PMID- 8515379 TI - Survey of socioeconomic and medical implications of diabetes and the lower limb. PMID- 8515380 TI - Modified calcaneal axial view. PMID- 8515381 TI - [Dielectric behavior of isolated rat submandibular glands: simulation with a vesicle-inclusion cell model]. AB - In an attempt to correlate the passive electrical properties of the secretory tissue with its structure, I measured AC admittances for isolated rat submandibular glands, over the frequency range between 100 Hz and 500 MHz. Animals were divided into three groups: control and treatment with two different secretagogues, isoproterenol and pilocarpine. Dielectric dispersions observed from control glands had two characteristic frequencies at 2.6 kHz and 59 kHz; the former was of the alpha-type and the latter of the beta-type. Secretagogue stimulated glands exhibited broader beta-dispersion curves. These dispersion data were analysed on the basis of a "two-shell model" with vesicle inclusions, in which two concentric shells represent the cell membrane and the nuclear envelope, and membrane-bounded vesicles are meant for secretory granules dispersed in the inter-shell space. Simulation by this model generated a good fit to data from the three groups. The analyses revealed that: (i) electric capacities for the cell and granular membranes were 2.1 and 0.9 microF/cm2, respectively; (ii) the conductivity of extracellular matrix was close to that of blood plasma; (iii) the conductivity ratio between cytoplasm and extracellular matrix was approx. 0.4; and (iv) the conductivity ratio between intragranular space and cytoplasm was approx. 0.7. PMID- 8515382 TI - Morning variations of plasma homovanillic acid in untreated schizophrenic patients. AB - Plasma concentrations of homovanillic acid were determined in samples obtained at 8.30 a.m. and 12.30 p.m. from 29 untreated schizophrenic patients, 14 males and 15 females. When the earlier samples were compared with the later, a significant decrease in mean plasma homovanillic acid level was observed, but only in the male patients. The morning fall was observed in 10 of 14 male patients and 6 of the 15 female patients. This morning rhythm in plasma homovanillic acid concentration may mask the putative rises in plasma homovanillic acid provoked by neuroleptic administration and may explain some of the observed differences between findings in studies involving the assessment of this metabolite. PMID- 8515384 TI - Deficits of the automatic orienting of attention in schizophrenic patients. AB - The automatic orienting of attention was studied in medicated non-psychotic schizophrenic patients and in matched controls using the Posner paradigm of covert orienting to peripheral cues. This paradigm allows determination of the "benefits" in performance when attention is moved in advance to target location ("valid" trials) and the "costs" in performance when attention has to be reoriented to target location after an incorrect directional cue ("invalid" trials). Compared to normals, schizophrenics showed reduced costs of invalid cueing and increased benefits of valid directional cueing. Schizophrenics did not show selective visual field asymmetries reported in similar studies. The decreased inhibition in the presence of incorrect directional cues may be related to a reduced tone of monoaminergic terminals possibly involved in the regulation of selective attention and arousal regulation. PMID- 8515383 TI - Measuring anxiety states in the elderly using the State-trait Anxiety Inventory for Children. AB - Healthy elderly persons aged 60 to 95 years were administered the Children's State version of the State-trait Anxiety Inventory (STAIC-S), the Geriatric Depression Scale (GDS) and the Minimental State Examination (MMSE) in order to establish descriptive data on the STAIC-S for use with a geriatric population. The STAIC-S was found to be internally consistent and temporally stable over an average of 11 days. In addition, factor analysis and correlations with the GDS and MMSE are presented. The authors suggest that the STAIC-S is both reliable and valid when used with an elderly population. PMID- 8515385 TI - An exploration of the relationship between expression of hostility and the anxiety disorders. AB - The purpose of the present study was to investigate differences between four anxiety disorder groups with respect to their levels of hostility. Patients with diagnoses of panic disorder, agoraphobia with panic, generalized anxiety disorder and social phobia were compared as regards their performance on the Hostility and Direction of Hostility Questionnaire (HDHQ). Results showed that while the groups did not differ on their extrapunitiveness, there were significant differences on intropunitive scores, with social phobics showing the most self criticism and guilt, followed in order by the agoraphobics with panic, generalized anxiety disorder and panic disorder subjects. Scores on the Anxiety Symptoms and Consequences Scale were used to predict intropunitiveness and extrapunitiveness for each diagnostic group. Results showed that intropunitiveness was related to anxiety symptoms differently for each diagnostic group. Overall, the study indicates that intropunitive hostility may be an important feature of anxiety disorders, especially panic with and without agoraphobia, and that the finding is worth further exploration with longitudinal studies. PMID- 8515386 TI - Relatedness of schizotypal personality to schizophrenic disorders: multifactorial threshold model. AB - Genetic analysis of schizophrenia and schizotypal personality disorder (SPD) was conducted on two pedigree samples. The results are interpreted in terms of a multifactorial threshold (MFT) model. A high rate of schizophrenia was found in relatives of both samples, but any excess of SPD was found only in relatives of the SPD sample. Based on these data, the hypotheses assuming a single liability with two thresholds (Reich's model) and different liability (Smith's model) for both disorders were rejected. The coefficient of genetic correlation is 0.61. Our data suggest that schizophrenia and SPD are separate nosological entities and that some of the factors which constitute liability to SPD influence the development of schizophrenia, but not vice versa. PMID- 8515387 TI - Family size and depressive symptoms in orthodox Jewish women. AB - Family size, religiosity and contextually-assessed stress were examined in relation to 11 symptoms of depression in Jewish women. Some indices of family size related to the absence of some symptoms. Notably, having pre-adult children was associated with absence of hopelessness. Religiosity and family size were highly confounded but the effects of the two did differ. Religiosity related to the absence of several symptoms: these were generally different from the symptoms associated with low family size. The data show that the associations between family size and religiosity, and depressive symptoms, cannot be explained in terms of lowered levels of stress. PMID- 8515388 TI - Neuromotor deviation in offspring of psychotic mothers: a selective developmental deficiency in two groups of children at heightened psychiatric risk? AB - As part of a longitudinal investigation begun in the neonatal period, selected neuromotor behaviors and different facets of general mental development were investigated blind at 6 years of age in 64 index offspring of women with a history of schizophrenic, schizoaffective, affective and unspecified functional psychosis and in 95 control offspring of women with no history of psychosis. Compared with the controls, the offspring of psychotics (total index group) showed a significantly increased frequency of both multiple and specific neuromotor deviations. The offspring of women with schizophrenia and with unspecified functional psychosis showed increased rates of multiple neuromotor deviations, not found in the offspring of women with schizoaffective and affective psychoses. The neuromotor deviations were confirmed on Griffiths Developmental Test subscales reflecting gross and fine motor performance, and the deficits did not extend to subscales measuring cognitive ability and personal social competence. No relationship was found between the individual subject's neonatal and 6-year deviation scores. The results suggest the existence of a selective neuromotor developmental deviation in the offspring of schizophrenics and women with unspecified functional psychosis. Different possible etiological factors are discussed. PMID- 8515389 TI - Generalized anxiety disorder patients seek evaluation for cardiological symptoms at the same frequency as patients with panic disorder. AB - Although panic disorder (PD) and generalized anxiety disorder (GAD) have similar somatic symptoms, panic attacks with chest pain and/or palpitations may seem more likely to be mistaken for heart attacks because of their acute onset. One would therefore expect that PD patients are more likely than GAD patients to seek cardiological consultations. In a survey of 146 PD and 154 GAD patients entering a multi-site drug trial, we found virtually identical rates of such consults. Approximately 50% of each patient group sought medical evaluation for cardiac symptoms. Furthermore, 40% of each group had standard treadmill evaluations and 33% reported having an echocardiogram. This study suggests that future epidemiological studies in cardiology populations should include probes for generalized anxiety disorder. PMID- 8515390 TI - Imipramine treatment of panic disorder with agoraphobia: the second time around. AB - The purpose of the present study was to assess and compare the therapeutic effects of imipramine during the initial treatment and retreatment of panic disorder with agoraphobia patients. Seven women with panic disorder with agoraphobia who had shown a marked and stable response to imipramine (121.4 +/- 41.8 mg/day) during their initial treatment of 24 weeks were retreated with the same dose (125 +/- 40.8 mg/day) of imipramine when they relapsed, on average 3 months following discontinuation of the drug. Assessments included operationalized criteria for response and relapse and plasma drug concentrations to verify treatment compliance. Data on phobic, panic, anxiety and depression measures were analyzed for 6 assessment times common to all patients; pretreatment, week 8 and 24 weeks follow-up of initial treatment, relapse which was also the beginning of retreatment, week 8 and 16-24 weeks follow-up of retreatment. At the end of retreatment all patients were marked responders and there was no significant difference on any outcome measure between the end of initial and retreatment assessment periods. However, overall therapeutic response to retreatment was slower than during initial treatment, in particular on phobic and patient rated panic measures. Although the full restoration of remission is clinically reassuring, the results caution that relapse may have sensitizing effects which delay, and if repeated could impede the response of panic disorder with agoraphobia patients to imipramine. PMID- 8515391 TI - Word associations and schizophrenic symptoms. AB - This study investigated the relationship between performance on a word association task and positive and negative symptoms of schizophrenia. Subjects were fifty inpatients with diagnoses of schizophrenia who were rated for positive and negative symptoms using the Positive and Negative Syndrome Scale. In a single word association task, negative symptoms correlated significantly with idiosyncratic responses; correlations with positive symptoms were not significant. When asked to place their stimulus word-association pairs in the context of a meaningful sentence, 65% of positive syndrome patients and 53% of negative syndrome patients were able to do so in such a way that their idiosyncratic associations were rated as meaningful in the context of a sentence. Negative symptoms were correlated with idiosyncratic associations that could not be used in a related sentence while positive symptoms were correlated with the inability to use common associations in a related sentence. Differential ability to use common and idiosyncratic associations in a related sentence suggests the possibility of two different patterns of language disturbance associated with positive and negative symptoms. PMID- 8515392 TI - Differential hemisphere processing of information in schizophrenia. AB - Ten paranoid and 10 nonparanoid schizophrenics, 10 nonschizophrenic psychiatric controls, and 10 normal controls were presented with two types of dot enumeration task, structured and unstructured dot arrays, tachistoscopically. The tasks were designed to elicit left and right hemisphere functioning through automatic and controlled information-processing strategies. The findings indicated that the two tasks failed to separate information-processing strategies as intended. The display size effects were found to be significant in both tasks for all the groups. In the case of the structured task, paranoids and nonparanoids both performed significantly more accurately in the right as compared with the left hemisphere. Unlike the other three groups, the nonparanoid group was found to process the dots in both tasks using an automatic strategy but this was so only in the left hemisphere. In the right, they performed like other groups. The findings thus point to a left hemisphere deficit in the nonparanoids. PMID- 8515393 TI - Long-term effects of repeated electroconvulsive shock on exploratory behaviour and seizure susceptibility to lidocaine in rats. AB - Electroconvulsive shock (ECS) has anticonvulsant properties while a proconvulsant effect has not, so far, been documented. In the present experiments, we determine whether repeated ECSs lead to an increased seizure susceptibility to lidocaine (lignocaine) in rats. Furthermore, we investigated whether ECS will cause prolonged changes in the locomotion and exploratory activity of the animals. Two groups of rats received 18 ECSs: the first group (ECS-WEEKLY) was given ECS once a week, the second (ECS-DAILY) once a day. A third group (ECS-SHAM) received only sham ECS. Five, as well as 10 weeks after the last ECS, the ECS-WEEKLY group made significantly fewer "hole visits" in an eight hole box than did the ECS-SHAM group. The ECS-DAILY group also made fewer hole visits than the ECS-SHAM group, but the difference was only significant ten weeks after the last ECS. No significant difference in locomotor activity was found. Twelve weeks after the last ECS, all rats received an injection of a high dose of lidocaine (65 mg/kg i.p.). ECS was observed to have a significant effect on the number of animals convulsing in response to the lidocaine challenge. Sixty percent (6/10) of the animals in the ECS-WEEKLY group and 20% (2/10) of those in the ECS-DAILY group convulsed, whereas none of the animals (0/12) in the ECS-SHAM group had convulsions. Thus, the present study shows that ECS may induce prolonged changes in the exploratory behaviour of rats and in their sensitivity to the convulsant effects of lidocaine. PMID- 8515394 TI - Secular trends in lifetime onset of MDD stratified by selected sociodemographic risk factors. AB - We used multivariate proportional hazards (Cox) models to investigate the effects of cohort of birth on age of first onset of major depression measured independently at two occasions, about six years apart, in the first degree relatives of probands with major affective illnesses. We estimated the cohort trends in strata defined by sociodemographic and other measures, to see if the cohort trends are the same across strata. Graphical summaries of the trends reveal a generally consistent pattern of increasing rates and earlier age of onset with successive birth cohorts, across all strata examined. The relatives with a divorced parent had a somewhat delayed secular increase, suggesting either a ceiling effect or an interaction of the two risk factors (recent cohort of birth and divorced parents) such that the combined effect is less than the sum of the individual effects. Otherwise, the cohort effect is persistent and ubiquitous in this sample. PMID- 8515395 TI - Use of the 3M precise microvascular anastomotic system in grafting 1-mm diameter arteries with polytetrafluoroethylene prostheses: a long-term study. AB - The 3M Precise Microvascular Anastomotic System has had an experimental long-term testing for the first time in polytetrafluoroethylene (PTFE) 1-mm diameter arterial grafts. The grafts were placed in the infrarenal aorta of 48 rats. At different time intervals (2 weeks, 16 weeks and 1 year), each section containing a graft and its pair of anastomotic devices was removed and processed for light and scanning electron microscopy, with the aid of a newly-designed device. Eighty three percent of the mechanically anastomosed grafts were found to be patent. Only 14.8 percent of the grafts harvested at 16 weeks or 1 year showed neo endothelial lining on the inner surface of the graft. A constant finding of this study was the marked atrophy of the aortic media within the devices, that was progressively evident from 2 weeks to 1 year. A network of capillaries within the graft walls was present at 16 weeks. In one case, a large capillary was found to traverse the graft wall and to reach the luminal surface, suggesting that transmural capillaries may contribute to the formation of neo-intima in 1-mm PTFE grafts. PMID- 8515396 TI - Microvascular anastomoses in growing vessels: a long-term evaluation of nonabsorbable suture materials. AB - Diametric growth at the anastomotic site, following microvascular anastomoses in pediatric patients, remains a problem, when nonabsorbable suture material is used. This study investigated the long-term effects of femoral artery anastomoses with nonabsorbable sutures in 20 growing rats with a mean weight of 101 g. The right femoral artery was anastomosed with 10-0 polypropylene monofilament suture and the left with identical nylon suture, using 5 to 6 interrupted sutures for each end-to-end anastomosis. At a 6-month harvest, the mean body weight had increased by 729 percent and the diameter of the femoral artery by 240 percent. The patency rate at the anastomotic sites was 97.5 percent and the complication rate was 10 percent, including one occlusion and three aneurysm formations at the sites. Angiography, diameter measurement, and histology demonstrated no stenosis or thrombus formation in all animals. Histology also showed normal vessel lumen size and well-organized re-endothelialization, without intimal hyperplasia at the anastomosis sites. With an interrupted suture technique, nonabsorbable sutures do not compromise growth at the anastomosis site or long-term patency of the anastomosed vessels. This study indicates that interrupted nonabsorbable suture materials are able to create excellent long-term results in microvascular anastomoses in rapidly growing hosts. PMID- 8515397 TI - The sticker-type temperature indicator in digital replantation: simplified application. AB - A sticker-type skin-surface temperature indicator, commercially available in Japan, has been utilized to monitor temperature changes in replanted digits. In clinical application, the authors evaluated several shortcomings in some of these devices. For example, the 10-mm diameter indicator is too small for numbers to be seen clearly. The 18-mm diameter indicator is too large to patch onto the finger pulp. To improve this device, the authors used only the number 33 from the 18-mm diameter indicator and applied it to several study subjects. Judgments about the circulatory status of the replanted digit can be made on the basis of the indicator color. The 18-mm diameter indicator, now modified to use only the number 33, is in common use for all the authors' digital replantation cases. Clinicians' ability to see critical temperature changes has been markedly improved, even under poor lighting conditions. PMID- 8515398 TI - The additive beneficial effect of UW solution and urokinase on experimental microvascular free-flap survival. AB - Pharmacologic manipulation of free flaps to enhance tolerance to ischemia has become a subject of great interest in the research literature. In an effort to improve survival, perfusion washout of experimental free flaps was performed following an episode of primary ischemia. The perfusates utilized were lactated Ringer's solution (LR), University of Wisconsin solution (UW), a high-molecular weight medium used in organ preservation, and urokinase, a thrombolytic agent. Seventy-five rats were used in this study and divided into groups of 5 each. A 3 x 6-cm abdominal free flap based on the superficial inferior epigastric vessels was raised in each rat. The free flaps were subjected to either 12 or 18 hr of primary ischemia. Following the period of ischemia, perfusion washout was performed with either LR, UW solution, or urokinase at increasing concentrations alone or in combination with UW solution. Urokinase was first evaluated as a perfusate alone at increasing concentrations. In the 12-hr ischemia group, free flap survival was shown to increase from 0 percent in the LR-perfused flaps to 20 percent, 60 percent, and 80 percent in flaps perfused with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). A similar increase in survival was demonstrated in the 18-hr ischemia group, where 0 percent, 20 percent, and 40 percent of flaps survived following perfusion with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). Urokinase was then perfused along with UW solution to evaluate the combined effect on flap survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515399 TI - Experimental diode laser-assisted microvascular anastomosis. AB - An experimental study to evaluate a diode-laser approach to microvascular end-to end anastomoses is reported. Studies were carried out on the femoral arteries and veins of Wistar rats, and effective welding of vessel tissue was obtained at low laser power, by enhancing laser absorption with indocyanine green (Cardio-green) solution. The histologic and surgical effects of this laser technique were examined and compared with those of conventional microvascular sutured anastomoses. PMID- 8515400 TI - Sutureless laser-welded anastomosis of the femoral artery and vein in rats using CO2 and Nd:YAG lasers. AB - In a comparative study, it was demonstrated that sutureless, laser-welded, end-to end anastomoses in the rat femoral artery and vein are feasible, using either CO2 or Nd:YAG laser. Conventional microsurgical suture anastomoses served as the controls. Patency rates in experimental animals and controls were equal (96 to 100 percent). No aneurysms were observed. For successful laser welding, the anastomosis must be completely tension-free. In arteries, this was accomplished only by interposition of a graft from the contralateral artery. The absence of any foreign-body reaction and the saving in operative time support the use of sutureless laser welding. PMID- 8515401 TI - The effect of venous occlusion on the integration of vascularized cortical bone graft. AB - The biologic phenomena involved in the healing process of vascularized, cortical bone grafts, vascularized grafts with venous occlusion, and conventional cortical bone grafts, were studied in rabbits. The middle third of the radial diaphysis was the donor site, with a 1.6-cm-long bone cylinder delimited by double transverse osteotomies. The vascularized grafts were raised by extraperiosteal dissection, with preservation of their vascular pedicle, while the conventional grafts were obtained by subperiosteal dissection. The vascularized graft with venous occlusion had its draining vein ligated. Radiologic, scintigraphic, and histologic studies were undertaken at days 7, 15, 30, and 60 postoperatively. Results demonstrated that the vascularized graft healed earlier than the corresponding vascularized graft with venous occlusion and than the conventional graft, respectively. The vascularized graft with venous occlusion suffered some degree of impairment of its irrigation, probably due to retrograde block of the arterial blood flow. It underwent a degree of bone necrosis, followed by resorption and creeping substitution, which delayed its integration. This seemed to be a temporary effect, for it healed earlier than the conventional graft. PMID- 8515402 TI - Fracture through united vascularized bone grafts. AB - The secondary fracture rate in 53 patients undergoing vascularized bone transfer for long-bone reconstruction, with a follow-up period of at least 2 years, is evaluated in this report. Twelve fractures occurred in 10 patients. Characteristics of the fractures were: (1) most occurred at the tibia recipient site; (2) most occurred through the transferred vascularized bone segment, rather than at its junctions; and (3) all fractures occurred within 1 year following bone union. When the fracture occurred in adults, union was relatively easily obtained by application of simple external fixation; on the other hand, union was difficult to obtain in patients with congenital pseudarthrosis of the tibia. PMID- 8515403 TI - Origin of Schwann cells in peripheral nerve allografts in the rat after withdrawal of cyclosporine. AB - The origin of Schwann cells in peripheral nerve allografts following rejection was determined by immunohistochemistry. Sciatic nerve allografts from ACI-RT1a rats were transplanted into Lewis-RT1l sciatic nerves using epineurial sutures. Isografts were taken from Lewis-RT1l rats. Cyclosporine (CsA) was administered subcutaneously daily, 5 mg/kg for 12 weeks, to the rats in each group. Allografts with CsA were sacrificed in groups at 12, 14, 16, 20, 24, and 36 weeks postoperatively during the rejection and recovery phase. Allografts and isografts without CsA were evaluated at 3, 6, 12, and 24 weeks. Nerves were frozen and cross sections immunohistochemically stained against Lewis rat HLA (RT1) and against Schwann cells (S-100 antigen). Allografts without CsA demonstrated minimal reaction to anti-Lewis compared to control isografts, which stained positively at all times. Schwann cells were not as well-stained in the allografts. Allografts with CsA showed reactivity to S-100 at 12 weeks, but minimal activity to Lewis antibody. Minimal reactivity to both S-100 and Lewis existed at 16 weeks, but increased gradually by 24 and 36 weeks. Therefore, Schwann cells from the recipient migrate into the graft and replace the Schwann cells from the donor following rejection. PMID- 8515404 TI - Doppler duplex for the evaluation of the degree of stenosis in carotid arteries in the rat. AB - This study evaluates the accuracy of the Doppler duplex technique for providing reliable information about the level of stenosis in microanastomoses. Stenoses ranging between 30 and 85 percent of the cross-sectional area of carotid arteries were evaluated in rats. Peak systolic velocities were measured in prestenotic, stenotic, and poststenotic segments, using the duplex technique. Surgical results with duplex measurements were expressed as percentage of stenosis (calculated from a ratio of two cross-sectional areas), and later correlated. The correlation coefficient between the two sets of measurements was 0.82 (p < 0.01), and the hypothesis of a simple linear relationship was clearly accepted (p = 0.92). Results of the study show that duplex measurements become increasingly unreliable in stenoses with severity less than 50 percent. With increasing degrees of stenosis (50 percent and above), the variance of measurements with duplex decreases. According to the data, the limiting value for the duplex method appears to lie at about 85 percent. When methods for continuous measurement of flap perfusion indicate a hindrance of inflow, Doppler duplex can provide valuable information about the causes. This technique can be used clinically for the evaluation of microanastomoses in 1-mm vessels. In clinical cases, if a 50 percent or more stenosis is diagnosed by duplex technique, the measurement should be repeated within 1 to 2 hr. If the stenosis persists or intensifies, revision should be considered. PMID- 8515405 TI - Interposition vein grafting in head and neck reconstructive microsurgery. AB - To characterize the role of interposition vein grafts, and to determine whether their use significantly influences the success of free tissue transfers in head and neck cancer reconstruction, we reviewed 191 consecutive cases with defects involving the aero-digestive tract soft tissues (80), the mandible (75), craniofacial resections (25), or cutaneous coverage (11). One hundred twenty patients had received prior loco-regional therapy, including 63 patients with recurrent lesions. Interposition vein grafts were used for the artery (11), vein (3), or both (3) in a total of 17 cases. The overall technical success rate was 93.2 percent (178/191). Cases in which vein grafts were used had a significantly (p < 0.001) lower success rate, 70.6 percent (12/17), than those without vein grafts, 95 percent (166/175). Grafts were most often used in patients who had received prior therapy (13/17). The use of vein grafts was associated with a significantly higher incidence of flap failure in head and neck cancer reconstruction; however, a causal relationship is not suggested. PMID- 8515406 TI - Transplantation of a cryopreserved hindlimb in the rat. PMID- 8515407 TI - The oral health status among residents of the Magadan Oblast, Russian Far East. AB - In April 1991, an oral health situation analysis team comprising oral health professionals from the Alaska Area Native Health Service, the World Health Organization, and the Moscow Medical Stomatological Institute visited the Magadan region of the Soviet Far East at the request of the Ministries of Health of both the Russian Republic and the then-Soviet Union. As few oral health data had been available specific to the Magadan region, the purpose of the trip was to gather data concerning oral diseases epidemiology, demography, and health systems of the communities of Magadan, Seymchan, and Provideniya as the basis for recommendations and plan development. The data were collected using standard WHO methodology. The analysis team examined children in the age cohorts of 3-5, 6-7, 12, and 15 years. In addition, adults aged 35-44 and 65-74 years were examined in Magadan and Seymchan. Both caries and periodontal rates are high, with a rate of 4.3 DMFT among 12-year-olds in the total region, but up to 5.4 DMFT in one location. Specific findings and recommendations have been forwarded to local community and health officials. The project is ongoing, and plans are underway to provide continuing assistance in designing and implementing an effective program for the prevention and treatment of oral diseases. PMID- 8515408 TI - Dental manpower planning in the Indian Health Service. AB - As a public health agency, the Indian Health Service (IHS) must plan for the needs of the entire American Indian and Alaskan Native (AI/AN) population and distribute resources as equitably as possible. To facilitate this process, the IHS has developed a manpower planning model to provide for the distribution of dental providers based upon the dental needs of the AI/AN population and within the limits of annual appropriations of funds. This paper briefly describes the original IHS Dental Program manpower planning model and the development of modifications over time. The need-based approach to manpower planning developed by the IHS Dental Program has exhibited utility and flexibility over time. It allows a determination of clinic size (number of operatories) and dental staffing requirements, and may be generalizable to other public health programs if an accurate assessment of utilization rate and treatment need can be made for the defined population. Nonetheless, the availability of resources in public programs is subject to the compromises inherent in the political process; thus, the use of a manpower planning model alone may not be sufficient to ensure the equitable distribution of dental resources and dental providers. PMID- 8515409 TI - Future dental public health programs: forging community and academic collaborations. PMID- 8515410 TI - Vital signs: American Association of Public Health Dentistry, 1937-1992. PMID- 8515411 TI - 1992 Distinguished Service Award: Durward R. Collier, DDS, MPH. PMID- 8515412 TI - 1992 Special Merit Award: Robert Carl Faine, DDS, MPH. PMID- 8515413 TI - Values and health care reform. PMID- 8515414 TI - The influence of social, economic, and professional considerations on services offered by dentists to long-term care residents. AB - Many studies have focused on the disabilities and behavior of the elderly population in an attempt to explain the frequent reports of poor oral health among residents of long-term care (LTC) facilities, but little attention has been given to the experiences and opinions of dentists relating to the problem. This study was conducted to discover how dentists feel about older patients and about working in LTC facilities. A response to a questionnaire was obtained from 334 (55%) of the 603 dentists in Vancouver who treated adults. The responses were subjected to bivariate and multivariate analyses. Three models were constructed from factors that might interest a dentist in attending a patient in a facility; the factors in each model were ranked in order of importance. Interest was associated significantly with lack of concern for time lost in practice, with training in managing medically compromised patients, and with a positive attitude toward elderly patients. Dentists with fewer years in practice were attracted by the economic potential of the service, while the older and busier dentists were less involved because of the disruption to their practice and leisure. Dentists who made home visits also were more likely to be interested. The model based on professional considerations was superior to either the social or economic model in explaining an interest in the service. PMID- 8515415 TI - Beneath the surface of coronal caries: primary decay, recurrent decay, and failed restorations in a population-based survey of New England elders. AB - A cross-sectional study was conducted of the oral health status of a random sample of community dwelling elders, aged 70 and older, living within the six New England states. Four examining teams, each composed of a trained and calibrated dentist and a field technician, collected data during an in-home oral examination. The prevalence of carious, filled, recurrent decayed, and non carious but failed restored coronal surfaces was recorded. For the 1,151 respondents, the mean DFT was 6.16 (SD = 6.96) and the mean DFS was 18.83 (SD = 23.37), with 37.6 percent of the sample edentulous. Eleven percent of the population had 70 percent of the coronal decay. Males (OR = 2.2, CI = 1.3-3.8) and elders with less education (OR = 1.8, CI = 1.0-3.0) were at higher risk for three or more surfaces of coronal decay. Recurrent decay was present in 16 percent of the dentate population. However, more noncarious but failed restored coronal surfaces (332) were recorded in the population of New England elders than were surfaces of recurrent decay (234). The New England elders have higher rates of decay than New England children, although the rates matched those of previous national studies. The findings signal a need to develop targeted preventive regimens for older adults and greater understanding of dental treatment needs of elders. PMID- 8515416 TI - The relationship between dental utilization and preventive participation among a well-elderly sample. AB - Previous studies have shown that dental utilization by older people is lower than for the general population. This study hypothesizes that an elder's tendency toward participating in preventive health activities may be an important factor in explaining the likelihood of accessing the dentist. Subjects included 1,911 older individuals who enrolled in the UCLA Medicare Screening and Health Promotion Trial. All were interviewed about their utilization of preventive health services and participation in preventive behaviors. A recent dental visit was positively associated with all sociodemographic variables examined except age and sex. It was also related to health status questions and utilization of the preventive health services and health behaviors studied. Logistic regression analysis showed that both summary preventive health behavior and preventive service utilization variables were important factors in explaining a recent dental visit (model chi-square = 221.4, P = .001) along with income, not having a removable prosthesis, and perceiving the need for dental care. This study showed that dental utilization is related to older people's participation in other preventive activities. When in contact with older people, health care professionals should consider current oral and general preventive health status and encourage appropriate referral for preventive activities. PMID- 8515417 TI - Attitudes of college football officials regarding NCAA mouthguard regulations and player compliance. AB - The National Collegiate Athletic Association (NCAA) mandates the use of brightly colored, intraoral mouthguards by football players to reduce the frequency and severity of craniofacial and intraoral morbidity and mortality, and to enhance the ability of officials to observe player compliance. The purpose of this 12 question mail survey was to determine the attitudes of on-field game officials regarding current NCAA mouthguard regulations and patterns of utilization by college football players. The sample consisted of all 50 Big East Football Conference officials; a response rate of 100 percent was achieved. Only 42 percent of the officials reported observing all players in compliance, and quarterbacks were identified by others as the least compliant group (52%). The majority (88%) indicated that the 1990 rule for brightly colored mouthguards had been beneficial to them in determining player compliance, and 52 percent reported that this rule had resulted in more frequent use by these athletes. Nearly all officials (96%) indicated that they would issue a warning for noncompliance to the player or coach, rather than charging a timeout for a violation as prescribed by NCAA regulations. The majority (70%) believe current enforcement is appropriate, but expressed the opinion that coaches should be held more accountable for player compliance. PMID- 8515418 TI - Synthesis and evaluation of the antitumor activity of 4,5-diamino-substituted 1,2 benzoquinones. AB - A series of 4,5-diamino-substituted-1,2-benzoquinones were prepared from catechol and the corresponding secondary amines in high yield in a single step using copper complex formation to stabilize the intermediate. The cytotoxicity of the products under various conditions was evaluated using the EMT-6 mammary carcinoma cell line, and antitumor activity was tested in the L1210 murine leukemia. The 4,5-diaziridinyl-1,2-benzoquinone was a more potent cytotoxic agent than diaziquone (AZQ) and was very effective against the L1210 leukemia. The azetidine, pyrrolidine, and diethylamine derivatives were not effective antitumor agents. PMID- 8515419 TI - 1,3,4-Oxadiazole, 1,3,4-thiadiazole, and 1,2,4-triazole analogs of the fenamates: in vitro inhibition of cyclooxygenase and 5-lipoxygenase activities. AB - N-Arylanthranilic acids, known generically as the fenamates, are nonsteroidal antiinflammatory drugs (NSAIDs) that block the metabolism of arachidonic acid by the enzyme cyclooxygenase (CO). Substitution of the carboxylic acid functionality of several fenamates with acidic heterocycles provided dual inhibitors of CO and 5-lipoxygenase (5-LO) activities when tested in an intact rat basophilic leukemia (RBL-1) cell line. Compound 5b (IC50 = 0.77 microM (5-LO), 0.27 microM (CO)) which contains an 1,3,4-oxadiazole-2-thione replacement and 10b (IC50 = 0.87 microM (5-LO), 0.85 microM (CO)) which contains a 1,3,4-thiadiazole-2-thione are the most potent inhibitors of 5-LO and CO activities from these series. Both of these heterocyclic analogs of flufenamic acid are also active in carageenin induced rat footpad edema (CFE), a model of acute inflammation. When dosed orally the ID50s for 5b and 10b in CFE are 8.5 and 4.7 mg/kg, respectively. PMID- 8515420 TI - Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg Gly-Asp-Phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the Arg-guanidine of RGDX mimetics and the platelet GP IIb IIIa receptor. AB - Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5 (4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the receptor which could explain the dramatic increase in potency upon replacement with benzamidine. This hypothesis is supported by the observation of low inhibitory potency of the corresponding benzylamine (18) and no activity with the corresponding imidazoline derivative (19); plus, ab initio calculations on the respective complexes suggest that the benzamidine-carboxylate is more favorable than the guanidine-carboxylate interaction. The ED50 for the inhibition of ex vivo collagen induced platelet aggregation in the dog for SC-52012 (1) was 0.32 microgram/kg/min by iv infusion with a pharmacodynamic half-life for recovery of approximately 40 min. PMID- 8515421 TI - The solution conformation of (D)Phe-Pro-containing peptides: implications on the activity of Ac-(D)Phe-Pro-boroArg-OH, a potent thrombin inhibitor. AB - Ac-(D)Phe-Pro-boroArg-OH is a potent, competitive inhibitor of thrombin (Ki = 40 pM). 1H-NMR studies have shown that the peptide portion, -(D)Phe-Pro-, has secondary structure in aqueous solutions. This structure corresponds fairly closely to the structure of H-(D)Phe-Pro-ArgCH2Cl complexed to thrombin in the protein crystal structure (Bode, W.; et al. EMBO J. 1989, 193, 3467-3475.). These results indicate that, in addition to enthalpic interactions in the active site of the enzyme, there are significant entropic advantages in binding this molecule not previously recognized. We estimate that they contribute approximately 10-fold to binding. The structure we have observed can be explained by pi-pi interactions between the phenyl side chain of (D)Phe and the (D)Phe-Pro peptide bond. Assignment of structure is based first on the 0.8-1.2 ppm difference between the two Pro C delta protons. The magnitude of these chemical shifts are consistent with aromatic ring current-induced effects expected for distances in our structure. The structure was further defined by interproton distances and correlation times calculated by backtransformation and correction of the NOESY and ROESY data to the longitudinal and transverse cross relaxation rates. Analysis of the vicinal coupling constants show that Phe chi 1 is not fixed. Correlation times for the peptide side chains and backbone indicate that the phenyl ring and boroArg side chain possess various degrees of internal motion, and that the rest of the peptide has a fairly rigid conformation. PMID- 8515422 TI - Hypoxia-selective antitumor agents. 7. Metal complexes of aliphatic mustards as a new class of hypoxia-selective cytotoxins. Synthesis and evaluation of cobalt(III) complexes of bidentate mustards. AB - Nitrogen mustards coordinated to Co(III) are potential hypoxia-selective cytotoxins, since one-electron reduction to the Co(II) complexes greatly labilizes the Co-N bonds, causing the release of activated aliphatic mustards which can act as diffusible cytotoxins. Two series of Co(III) complexes of the bidentate bisalkylating nitrogen mustard ligands N,N'-bis(2-chloroethyl) ethylenediamine (BCE) and N,N-bis(2-chloroethyl)ethylenediamine (DCE) have been synthesized and evaluated for their hypoxia-selective cytotoxicity against AA8 cells in vitro. The complexes also bear two 3-alkylpentane-2,4-dionato (acac) auxiliary ligands; cyclic voltammetry studies show that variation of the alkyl group in the auxiliary ligands alters the reduction potentials of the complexes (within a series) over a range of about 150 mV. In both series, the patterns of cytotoxicities of the cobalt complexes were broadly similar to those of the respective free ligands, suggesting that the cytotoxicity of these compounds is due to release of the free ligands. The nonsymmetrical ligand DCE and its cobalt complexes were 1 order of magnitude more cytotoxic than the corresponding BCE compounds. Although the unsubstituted acac/DCE complex showed no hypoxic selectivity against repair-deficient UV4 cells in a stirred suspension culture assay, the methyl and ethyl analogues showed substantial selectivity. The results may indicate a narrow range of acceptable reduction potential, with an optimum close to that for the methyl analogue (E1/2 = -305 mV). The methyl analogue also shows hypoxic selectivity against repair-proficient cell lines (e.g., AA8 and EMT6) and has high activity against EMT6 cells in intact spheroids, suggesting that the released DCE is capable of back-diffusion from the hypoxic core of the spheroid. This work shows that metal complexes of nitrogen mustards have significant hypoxia-selective cytotoxicity toward mammalian cells in cell culture and are a new general class of hypoxia-selective cytotoxins. PMID- 8515423 TI - Structure-based design of inhibitors of purine nucleoside phosphorylase. 2. 9 Alicyclic and 9-heteroalicyclic derivatives of 9-deazaguanine. AB - Alicyclic and heteroalicyclic derivatives of 9-deazaguanine (2-amino-1,5-dihydro 4H-pyrrolo[3,2-d] [pyrimidin-4-one) are, with one exception, potent inhibitors of purine nucleoside phosphorylase (PNP) equaling the corresponding 9-arylmethyl derivatives previously investigated. The mode of binding of these compounds to PNP was determined by X-ray crystallography. PMID- 8515424 TI - Molecular model of the interaction of bee venom phospholipase A2 with manoalide. AB - A molecular model of the interaction between manoalide (MLD) and bee venom phospholipase A2 (bv-PLA2) has been derived making use of a combination of computational methods. MLD was built in its open form and simulated by using molecular dynamics techniques. It is shown that the polar part of the molecule, which is thought to be the reactive region, is endowed with considerable conformational flexibility whereas the apolar region is rather rigid. The proposed active conformation of MLD and the main putative binding site for MLD on this enzyme were identified by matching potential energy GRID maps for both ligand and receptor with the chemical structure of the respective counterpart. The binding site is found in the C-terminal region of bv-PLA2, forming part of the proposed interfacial surface for binding to aggregated substrates, and comprises two distinct regions: (i) a hydrophobic cavity delimited by the C terminal beta-sheet and the antiparallel beta-sheet, which interacts with the apolar zone of MLD, and (ii) a cationic site made up of residues Arg-58 and Lys 94, which interacts with the polar zone. Molecular dynamics and molecular orbital calculations indicate that the most likely initial reaction between MLD and bv PLA2 is formation of a Schiff base between Lys-94 and the aldehyde generated upon opening of MLD's gamma-lactone ring, supporting recent model reaction studies. The inhibition seems to be a consequence of the occupation by MLD of a site overlapping a phosphocholine binding site in bv-PLA2 presumably involved in the interface desolvation process. The present model represents a starting point for further structural studies on the mechanism of phospholipases A2 inactivation by MLD and MLD-like compounds. PMID- 8515425 TI - Potent nonpeptide angiotensin II receptor antagonists. 2. 1 (Carboxybenzyl)imidazole-5-acrylic acids. AB - The further evolution of the imidazole-5-acrylic acid series of nonpeptide angiotensin II receptor antagonists is detailed (for Part 1, see: J. Med. Chem. 1992, 35, 3858). Modifications of the N-benzyl ring substitution were undertaken in an effort to mimic the Tyr4 residue of angiotensin II. Introduction of a p carboxylic acid on the N-benzyl ring resulted in the discovery of compounds with nanomolar affinity for the receptor and good oral activity. SAR studies of these potent antagonists revealed that the thienyl ring, the (E)-acrylic acid, and the imidazole ring in addition to the two acid groups were important for high potency. Also, overlay comparisons of the parent diacid with both angiotensin II and a representative biphenylyltetrazole nonpeptide angiotensin II receptor antagonist are presented. The parent diacid analog, SK&F 108566 or (E)-3-[2-butyl 1-(4-carboxybenzyl)-1H-imidazole-5-yl]-2-[(2- thienyl)methyl]propenoic acid, is currently in clinical development for the treatment of hypertension. PMID- 8515426 TI - Inhibition and inactivation of presynaptic cholinergic markers using redox reactive choline analogs. AB - Inhibition and inactivation of two presynaptic cholinergic "markers", choline acetyltransferase and high affinity choline transporter, has been investigated using inhibitors designed with a redox-reactive catechol tethered to a quaternary ammonium group. Two quaternary ammonium alkyl-substituted catechols, 3[(trimethylammonio)methyl]catechol (TMC, 1) and N,N-dimethylepinephrine (catecholine, 2) were shown to bind weakly and noncompetitively to bovine choline acetyltransferase yet inactivated the enzyme in a time course consistent with the involvement of early intermediates in the spontaneous oxidation of these catechols. Both agents also inhibited high-affinity choline uptake. The time course of TMC and catecholine spontaneous oxidation-dependent inactivation of high affinity choline uptake sites was slower than, if it occurred at all, the spontaneous degradation of measurable choline transport in synaptosomes. When compared with inhibition of uptake of other neurotransmitters, it was shown that catecholine demonstrated more selectivity than TMC toward inhibition of choline transport. Km (microM) and Vmax (pmol/min per mg of protein) were measured for high affinity transport of choline, dopamine, and serotonin and were observed to be Km = 2.04 +/- 0.31, Vmax = 22 +/- 1; Km = 1.4, Vmax = 53; and Km = 0.15, Vmax = 23, respectively, in good agreement with published literature values. Ki's (mM) for catecholine and TMC, calculated from experimentally determined IC50's, were for catecholine 0.13 +/- 0.06, 0.53 +/- 0.09, and 0.39 +/- 0.10, and for TMC 0.06 +/- 0.03, 0.09 +/- 0.03, and 0.09 +/- 0.08, for choline, dopamine, and serotonin transport, respectively. In vivo studies using catecholine suggest that this compound impairs learning ability associated with long-term memory. Thus, catecholine represents a lead compound in a potential series of redox-reactive choline analogs, which may become useful irreversible antagonists of the critical cholinergic macromolecular targets underlying cholinergic hypofunction in disorders such as Alzheimer's disease. PMID- 8515427 TI - Multiple binding modes for the receptor-bound conformations of cyclic AII agonists. AB - Angiotensin II, Asp-Arg-Val-Tyr-His-Pro-Phe, binds its receptor with a postulated turn centered at residue four. Analogs of angiotensin II which contain a disulfide bridge between the side chains of residues 3 and 5 retain significant activity consistent with this hypothesis. Incorporation of 4-mercaptoproline residues, a hybrid, or chimeric amino acid which combines the properties of proline and homocysteine, into either of these positions with analogous disulfide bridges allows retention of high affinity for the receptor. These more highly constrained bicyclic systems give new insight into the details of molecular recognition of residues 3-5 of angiotensin by the receptor. Retention of activity by the antiparallel dimer of [Sar1,Cys3,5]-AII in which the peptide backbone is held in an extended conformation was unexpected. Analysis of the conformational constraints imposed in these active analogs suggests that AII agonists bind to their receptor with different backbone conformations in the region of the central tyrosine residue. PMID- 8515428 TI - Enantioselectivity of cocaine recognition sites: binding of (1S)- and (1R)-2 beta carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) to monoamine transporters. PMID- 8515429 TI - (+/-) 3-Amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole: a conformationally restricted analogue of 5-carboxamidotryptamine with selectivity for the serotonin 5-HT1D receptor. PMID- 8515430 TI - Simulation of the light-induced oscillations of the membrane potential in Potamogeton leaf cells. AB - An attempt has been made to simulate the light-induced oscillations of the membrane potential of Potamogeton lucens leaf cells in relation to the apoplastic pH changes. Previously it was demonstrated that the membrane potential of these cells can be described in terms of proton movements only. It is hypothesized that the membrane potential is determined by an electrogenic H(+)-ATPase with a variable H+/ATP stoichiometry. The stoichiometry shifts from a value of two in the dark to a value of one in the light. Moreover, this H+ pump shows the characteristics of either a pump or a passive H+ conductance: the mode of operation of the H+ translocator is considered to be regulated by the external pH. The pump conductance is assumed to be dominant at low or neutral pH, while the passive H+ conductance becomes more significant at alkaline pH. The pH dependence of the transport characteristic is expressed by protonation reactions in the plasma membrane. The proposed model can account for most features of the light-induced oscillations but not for the absolute level of the membrane potential. PMID- 8515431 TI - Characterization of ion channels from Acetabularia plasma membrane in planar lipid bilayers. AB - Plasma membrane from Acetabularia acetabulum was prepared by aqueous-polymer two phase partitioning and incorporated into planar 1-palmitoyl-2-oleoyl phosphatidylethanolamine bilayers by stirring in the presence of a (cis:trans) 325:100 mM KCl gradient. Under these conditions five distinct K(+)-selective channels were observed which had unitary chord-conductances (determined between 30 mV either side of the reversal potential) and frequencies of incorporation (in parentheses) of 1,600 pS (26%), 485 pS (21%), 259 pS (53%), 140 pS (37%) and 27 pS (37%). Two Cl(-)-selective channels were also observed, which had unitary chord-conductances of 8 and 48 pS and were present in 21 and 16% of bilayers, respectively. The voltage dependencies of channel open probability (Po), open state time constant (tau o) and closed-state time constant (tau c) were determined for the 259, 140 and 27 pS K+ channels. The Po of all three channels increased with increasingly positive membrane potentials. Thus, since these channels were oriented with their extracellular face adjacent to the cis chamber, which was grounded, all would exhibit outward rectification in vivo. Changes in Po were effected by modulation of tau c in all channels, which shortened as membrane potentials became more positive, and also of tau o in the 140 and 27 pS channels, which increased as membrane potentials became more positive. Extracellular (cis) KCl concentration (and/or the KCl gradient across the bilayer) affected the Po of all three K+ channels, shifting the Po/membrane potential relationship in the direction of the change in the potassium reversal potential. In all channels this was achieved largely by changes in tau c. PMID- 8515432 TI - A Gq-type G protein couples muscarinic receptors to inositol phosphate and calcium signaling in exocrine cells from the avian salt gland. AB - Muscarinic acetylcholine receptor (mAChR) activation in isolated cells from the nasal salt gland of the domestic duck (Anas platyrhynchos) results in a rapid increase in the rate of phosphatidylinositol hydrolysis and pronounced intracellular calcium signals. Both responses can be elicited by treating these cells with fluoroaluminate (AlF4-) indicating the involvement of a heterotrimeric G protein in the transmembrane signaling process. To characterize this G protein, electrophoretically separated membrane proteins were blotted onto nitrocellulose filters and probed with peptide-antibodies raised against portions of different alpha-subunits of mammalian G proteins. We could demonstrate the presence of at least four different G proteins in salt gland cell membranes. Two of these proteins (40 and 41 kD) were ADP-ribosylated by pertussis toxin and were recognized by an antiserum against a common sequence in all G protein alpha subunits. One protein (46 kD) was a cholera toxin-substrate and was recognized by a Gs-specific antiserum; the other (42 kD) was recognized by Gq-specific antisera and was resistant to ADP-ribosylation. Since the initial inositol phosphate production upon receptor activation with carbachol and the resulting calcium signals were not affected by pertussis toxin-pretreatment of salt gland cells, we conclude that muscarinic receptors are coupled to phospholipase C by a Gq-type G protein. PMID- 8515434 TI - Unbiased volume estimation with coaxial sections: an application to the human bladder. AB - A problem of current medical interest is how to estimate the volume of an object from coaxial sections. Such images can be produced in ultrasound scanning, when the planar scan sections all emanate from a common axis. Two unbiased volume estimators for this sampling regime, previously published without derivation, are derived and presented here in some detail. The estimators are based on an ancient theorem of Pappus of Alexandria (c. AD 320). One of the estimators was used to estimate the volume of urine in the bladder of six human volunteers. The case example was attractive because the corresponding volumes could be voided and directly measured after the scanning session, thus confirming the unbiasedness of the estimator used. Sample size guidelines are also given. PMID- 8515433 TI - Molecular species of membrane phospholipids containing arachidonic acid and linoleic acid contribute to the interindividual variability of red blood cell Na(+)-Li+ countertransport: in vivo and in vitro evidence. AB - Previous studies indicate a particular sensitivity of red blood cell Na(+)-Li+ countertransport activity to small variations in the fatty acid composition of membrane phospholipids. To assess whether the interindividual variability of Na(+)-Li+ countertransport is related to differences in the species pattern of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in vivo, the molecular species composition of PC and PE as well as the kinetics of Na(+) Li+ countertransport were analyzed in parallel in normo- and hyperlipidemic donors. Both in diacyl-PC and in diacyl-PE the species 16:0/20:4 and 16:0/18:2 were, respectively, positively and negatively related to the apparent maximal velocity of Na(+)-Li+ countertransport. The sum of all species with 20:4 at sn2 of diacyl-PE exhibited a strong positive (r = 0.82, 2p < 0.001), and those containing 18:2 a negative correlation (r = -0.63, 2p < 0.01) to the transport activity. Essentially similar connections were observed between these species and the apparent affinity of the transport system for intracellular Na+. To evaluate whether the associations between molecular species of membrane phospholipids and Na(+)-Li+ countertransport activity were indicative of a causal relationship, the species 16:0/20:4-PC and 16:0/18:2-PC were selectively introduced into the erythrocyte membrane by means of the PC-specific transfer protein. Replacement of 11% of native PC by 16:0/18:2-PC inhibited the transport rate by about 25%. Exchange of 6 and 9% of PC with 16:0/20:4-PC, in contrast, accelerated the transport rate by 30 and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515435 TI - Vertical LM sectioning and parallel CT scanning designs for stereology: application to human lung. AB - Practical, unbiased stereological methods are described to estimate lung volume and external surface area, and total volume and surface area of relatively large and anisotropic structures (bronchi and arteries) inside the lung. The volume of each of five lung strata was estimated first by fluid displacement and then by computed tomography (CT) using Cavalieri's method; the reliability of CT was assessed through a calibration procedure, and image thresholding criteria for an accurate volume estimation using CT were established. The parallel, perfectly registered CT section images were also used to estimate the external surface area of each stratum by the spatial grid method. Unbiased estimation of internal surface areas in lung is a long-standing problem: since the structures are large and essentially void, large sections are needed; to facilitate identification, thin sections have to be used for light microscopy, and since such structures are anisotropic, the sections should be vertical. A practical stereological design is demonstrated here on an infant lung, which fulfils all these requirements. This study illustrates the potential of using unbiased stereology to characterize infant pulmonary hypoplasia. PMID- 8515436 TI - An assessment of obstetric services in Mississippi. AB - Seven hundred and six (80.6% response rate) obstetricians, family physicians, and general practitioners responded to a survey designed to elicit information regarding their obstetric practice. Results of the study were compared to a similar survey conducted in 1985. The proportion of obstetricians offering obstetric care has remained relatively constant since 1985. Among family physicians and general practitioners, however, there was a significant decrease in the proportion who practice obstetrics (p < .01), and a significant increase in the proportion who have discontinued obstetric practice in the last five years (p < .01) and who plan to discontinue obstetric care in the next five years (p < .05). Consistent with the 1985 data, cost of malpractice insurance, threat of litigation, and time demand were the three most frequently reasons for discontinuing obstetric care. Without changes in the current system, the provision of obstetric care in rural areas will continue its current dramatic decline. PMID- 8515437 TI - Slipped capital femoral epiphysis, a problem of diagnosis. PMID- 8515438 TI - The spatial structure of the class II L-fuculose-1-phosphate aldolase from Escherichia coli. AB - The three-dimensional structure of L-fuculose-1-phosphate aldolase (FucA) from Escherichia coli was determined by X-ray crystallography at a resolution of 2.13 A. The enzyme is a homotetramer with an M(r) of 23,775 per subunit. Since its activity depends on the presence of metal ions (Zn2+) the enzyme belongs to the class II aldolases. As expected from amino acid sequence comparisons, this first structure of a class II aldolase shows no similarity to the known structures of class I aldolases. It has some unusual features concerning the overall chain fold, the quaternary structure, and the co-ordination of the catalytically active zinc ion. A sequence comparison with the data bank indicated that the middle domain of the enzyme L-ribulose-5-phosphate-4-epimerase is homologous to FucA and may contain an active-center metal ion. PMID- 8515439 TI - Asp ligand provides the trigger for closure of transferrin molecules. Direct evidence from X-ray scattering studies of site-specific mutants of the N-terminal half-molecule of human transferrin. AB - Recent X-ray crystallographic and solution X-ray scattering studies have shown that transferrins (serum transferrin, lactoferrin and ovotransferrin) undergo a major conformational change when iron is incorporated into the molecule. Apo proteins show a structure with open interdomain clefts which close when iron is bound. The closed conformation has been suggested as an important step in the receptor recognition. Here, we report X-ray solution scattering experiments of the mutated N-terminal fragment of human serum transferrin with Asp63-->Ser (Cys). The data provide the first direct experimental evidence for the existence of a trigger mechanism for the closure of the interdomain cleft and that this trigger mechanism is disrupted by mutation of Asp63, the only ligand of iron from domain I. PMID- 8515440 TI - Self-splicing of a Podospora anserina group IIA intron in vitro. Effects of 3' terminal intron alterations on cleavage at the 5' and 3' splice site. AB - A shortened derivative of the group IIA intron from the mitochondrial cytochrome c-oxidase subunit I gene (COI I1) of the ascomycete Podospora anserina can undergo self-splicing in vitro. When compared to self-splicing group IIB introns from yeast mitochondria (aI5c, bI1) the autocatalytic reaction shows a lower efficiency and 5' cleavage takes place predominantly by hydrolysis. In order to test the influence on reaction efficiency and mode of 5' cleavage of the long peripheral structure of domain VI (dVI) we generated mutant Podospora introns that have different structural forms of shortened dVI. Our results show that: (1) in general the size and structure of dVI distal from the branch site is essential for 5' transesterification and influences the efficiency of the second splicing step; (2) 5' transesterification as well as the complete self-splicing reaction is more efficient when the structure of dVI is adapted to that of yeast group IIB introns. Moreover, our data indicate that the postulated gamma-gamma' tertiary interaction is also functional for group IIA introns. A weakening or disruption of this interaction in the Podospora intron leads to a greatly reduced cleavage at the 3' splice site and to a selection of cryptic sites downstream in the 3' exon that almost exclusively restore the strong wild-type gamma-gamma' pairing. The so-called "guide" interaction seems to support the selection of 3' cleavage sites but is of secondary importance in relation to the gamma-gamma' interaction. PMID- 8515441 TI - Coupling of rRNA transcription and ribosomal assembly in vivo. Formation of active ribosomal subunits in Escherichia coli requires transcription of rRNA genes by host RNA polymerase which cannot be replaced by bacteriophage T7 RNA polymerase. AB - Transcription of a plasmid-located rrnB operon and the corresponding formation of ribosomes in vivo were studied using either T7 RNA polymerase or host RNA polymerase as transcriptase. The 23 S rRNA gene on the plasmid carried an A1067- >T mutation, which confers resistance against the drug thiostrepton. The proportion of particles containing plasmid-borne 23 S rRNA versus chromosome borne rRNA was quantified with a precision of better than 10% by scanning sequence autoradiograms around nucleotide 1067. The activity of these particles was determined in the presence of thiostrepton which exclusively abolishes the activity of chromosomal wild-type ribosomes. When the plasmid rrnB operon was transcribed with phage T7 RNA polymerase, up to 80% of the rRNA synthesis was plasmid-directed (pulse labelling) in the late induction phase, most of which (about 85%) became degraded. The cells accumulated 50 S particles with plasmid borne intact rRNA that was hardly found in 70 S ribosomes, i.e. particles harbouring plasmid-borne rRNA did not enter the pool of active ribosomes. The particles with plasmid-derived rRNAs were also practically inactive in protein synthesis in vitro. However, the rRNA was functional as shown by reconstitution analysis. The same patterns were found at various expression levels of the plasmid rrnB operon, indicating that not the overproduction of rRNA but rather the T7 transcriptase was responsible for the observed effects. However, when the plasmid rrnB operon was transcribed with host RNA polymerase, growth was not affected upon induction, the 30 S to 50 S to 70 S ratios in the cell were not altered, both 50 S subunits and 70 S ribosomes contained large amounts of plasmid borne rRNA, and the particles with plasmid-derived rRNA were active in vitro. When the induction of rRNA transcription by T7 RNA polymerase was performed at 25 degrees C instead of 37 degrees C, an almost normal pattern was observed. Inactive 50 S particles did not accumulate, and large amounts of plasmid-borne rRNA were found in the pool of 70 S ribosomes. Lowering the induction temperature reduces the transcription rate by T7 RNA polymerase, which is five times faster at 37 degrees C than the host polymerase. The results suggest that the formation of active ribosomal subunits in vivo requires a fine adaptation of the transcription rate of rRNAs and the assembly process, underlining the importance of a coupling between rRNA transcription and ribosome assembly in vivo. T7 RNA polymerase cannot replace the host RNA polymerase in this process at 37 degrees C. PMID- 8515442 TI - Genetic and biochemical analysis of the integration host factor of Escherichia coli. AB - Integration host factor (IHF) is a small, heterodimeric DNA-binding protein of Escherichia coli composed of two subunits, alpha and beta, encoded by the himA and hip genes, respectively. IHF binds to the minor groove at a consensus sequence and bends DNA. We mutagenized the hip gene and studied the activity of the mutant IHF proteins in vivo and in vitro. Substitutions at the C-terminal alpha-helix (alpha-helix 3) reduced IHF activity and relaxed the specificity to DNA without abolishing the ability of IHF to bend DNA. These results indicate that the C-terminal region of Hip participates in determining IHF specificity. Alanine substitutions in beta-strands 2 and 3 generally had no effect on IHF activity in vivo suggesting that individually, many of these residues make only small contributions to the binding of IHF to DNA. Replacing the single amino acid of Hip that differs from HU in a highly conserved region of the arm did not affect IHF activity. This finding led us to conclude that this region of Hip does not contribute to specific DNA recognition by IHF. The binding of IHF to DNA is probably not restricted to one domain, but requires the co-operative participation of a number of regions of the protein. PMID- 8515443 TI - Structural and functional requirements for the chromatin transition at the PHO5 promoter in Saccharomyces cerevisiae upon PHO5 activation. AB - The PHO5 promoter from Saccharomyces cerevisiae can exist in two chromatin configurations depending on its state of activity. In the repressed promoter a short hypersensitive site containing a binding site for the transcription factor PHO4 is flanked by specifically positioned nucleosomes. After induction two nucleosomes upstream and two downstream of the hypersensitive site are disrupted, and the entire promoter becomes accessible. We have investigated mechanisms responsible for setting up the structure of the repressed state and for the transition. Episomal centromeric plasmids bearing the PHO5 promoter show the same chromatin structure as the endogenous chromosomal copy arguing that the chromosomal context is not essential and that the nucleosomal organization is not set up from a distance. Deleting most of the hypersensitive region including the PHO4 binding site also leaves the positioning of the adjacent nucleosomes in the repressed promoter unchanged indicating that histone-DNA interactions play an important role in setting up nucleosome positions. However, when half of the DNA of a nucleosome is deleted a new nucleosome forms at the same location with respect to the neighboring nucleosome indicating that boundary effects also contribute to nucleosome positioning in the native promoter. Disruption of the nucleosomes under activating conditions is shown to require interaction of PHO4 with its binding site located within the hypersensitive region. This disruption takes place also in two independent constructs in which the TATA box had been deleted and as a result the gene was not transcribed. This result shows for the first time that the generation of active chromatin at a regulated promoter is not the result of gene expression but occurs prior to transcription. PMID- 8515444 TI - An X-ray diffraction study of frog skeletal muscle during shortening near the maximum velocity. AB - Using an imaging plate exchanger and a synchrotron X-ray source, X-ray diffraction patterns were recorded from frog skeletal muscles shortening near the maximum velocity from a sarcomere length of 2.6 to 2.1 microns. The major findings were as follows: (1) the intensity of the second-order myosin meridional reflection, which decreased to 18% of the resting value during isometric contraction, increased to 34% during shortening, showing that the perturbation in the axial arrangement of myosin heads recovered. (2) The intensity of the third order myosin meridional reflection increased by 32% on isometric contraction and decreased to 51% of the resting intensity during rapid shortening, showing disorder in the axial rearrangement of the myosin heads. (3) The axial Bragg spacing of the third-order meridional reflection, which increased by 1.22% during isometric contraction, was still 0.47% larger than the resting value during shortening, indicating that the increase is not entirely due to extension of the filament by tension. (4) The intensity ratio of the (1,0) and (1,1) equatorial reflections increased a small extent (from 0.57 to 0.62) during shortening, while the 5.9 nm and 5.1 nm actin layer-lines showed large intensity decreases (126 to 101% and 190 to 124% of the resting intensity, respectively), suggesting that considerable numbers of myosin heads are in the vicinity of the thin filament but not tightly bound to actin molecules during rapid shortening. These results are consistent with a model of muscle contraction in which myosin heads attach to actin in two different manners with weak and strong affinities and show that, during shortening, the number of tightly attached heads decreases by half, while the total number of attached heads decreases only slightly. PMID- 8515445 TI - Protein-protein interactions during filamentous phage assembly. AB - Filamentous phage proteins pI and pIV are morphogenetic proteins required for phage assembly but not part of the virion. Neither pI nor pIV from the related phages f1 and IKe can substitute for its equivalent in the other phage. When the two proteins are supplied as pairs, however, partial restoration of heterologous phage assembly occurs. This observation strongly suggests that the two proteins interact. A selection for revertants of a temperature sensitive mutant of f1 gene IV resulted in the isolation of a suppressor mutation in gene I. This suppressor is allele specific, and thus supports the hypothesis that pI and pIV interact. A selection for IKe phage that can efficiently utilize paired pI and pIV from from f1 led to the isolation of a phage with a mutation in gene VIII, which encodes the major coat protein of the virus. Analysis of the system suggests that it is pI that interacts with both pIV and pVIII. Thus the process by which filamentous phage are concomitantly assembled and secreted across the cell membranes is likely to involve a series of protein-protein interactions that are accessible to genetic analysis. PMID- 8515446 TI - Three-dimensional structure of the tetragonal crystal form of egg-white avidin in its functional complex with biotin at 2.7 A resolution. AB - The three-dimensional structure of hen egg-white avidin, crystallized in a tetragonal crystal form, has been solved at 2.7 A resolution by molecular replacement methods. After refinement the crystallographic R-factor is 16.8%, for the 7255 reflections in the 10.0 to 2.7 A resolution range. The asymmetric unit contains two avidin polypeptide chains (M(r) 2 x 15,600), which build up the functional tetramer through a crystallographic 2-fold axis parallel to the c unit cell direction. The avidin tetramer has almost exact 222 molecular symmetry; the three possible dimers display quite distinct packing interfaces. Each protomer is organized in an eight-stranded antiparallel orthogonal beta-barrel, with extended loop regions. The avidin binding site within each promoter is located in a deep pocket, at the center of the barrel, displaying both hydrophobic and polar residues for recognition of the tightly bound vitamin. Two Trp residues, Trp70 and Trp97, and Phe79 are in close contact with biotin. Moreover, the binding pocket is partly closed in its outer rim by residue Trp110 of a neighboring subunit. Once bound, biotin is almost completely buried in the protein core, with the exception of the valeryl side-chain carboxylate group which is exposed to solvent, hydrogen bonds to residues Ala39, Thr40 and Ser75, and triggers the formation of a network of hydrogen bonded water molecules. Modeling of synthetic biotin analogues allows us to rationalize functional data available for the binding of these compounds, and to analyze them in terms of biotin recognition mechanism. Hen egg-white avidin shows clear structural homology to streptavidin, from Streptomyces avidinii, but significant deviations can be observed in some regions. PMID- 8515447 TI - High-resolution structure of calcium-loaded calbindin D9k. AB - The three-dimensional solution structure of calcium-loaded calbindin D9k has been determined using experimental constraints obtained from nuclear magnetic resonance spectroscopy. A total of 1176 constraints (16 per residue overall, 32 per residue for the core residues) was used for the final refinement, including 1002 distance and 174 dihedral angle constraints. In addition, 23 hydrogen bond constraints were used for the generation of initial structures. Stereospecific assignments were made for 37 of 61 (61%) prochiral methylene protons and the methyl groups of all three valine residues and five out of 12 leucine residues. These constraints were used as input for a series of calculations of three dimensional structures using a combination of distance geometry and restrained molecular dynamics. The 33 best structures selected for further analysis have no distance constraint violations greater than 0.3 A and good local geometries as reflected by low total energies (< or = -1014 kcal/mol in the AMBER 4.0 force field). The core of the protein consists of four well-defined helices with root mean-square deviations from the average of 0.45 A for the N, C alpha and C' backbone atoms. These helices are packed in an antiparallel fashion to form two helix-loop-helix calcium-binding motifs, termed EF-hands. The two EF-hands are joined at one end by a ten-residue linker segment, and at the other by a short beta-type interaction between the two calcium-binding loops. Overall, the average solution structure of calbindin D9k is very similar to the crystal structure, with a pairwise root-mean-square deviation of 0.85 A for the N, C alpha and C' backbone atoms of the four helices. The differences that are observed between the solution and the crystal structures are attributed to specific crystal contacts, increased side-chain flexibility in solution, or artifacts arising from molecular dynamics refinement of the solution structures in vacuo. PMID- 8515448 TI - Alignment and searching for common protein folds using a data bank of structural templates. AB - We introduce an approach to protein comparisons in which tertiary-structure information is exploited in the alignment of a protein sequence of known tertiary structure, or an aligned set of sequences of known homologous structures, with one or more sequences. The local tertiary environments of residues in the one or more three-dimensional structures (defined in terms of residue accessibility to solvent, secondary structure and hydrogen bonding) are used to select position specific amino acid substitution scores and produce a scoring template suitable for aligning sequences or searching sequence data banks. The amino acid substitution scores have been accumulated from 72 families of protein structures in which the observed substitutions have been classified according to features of the local structure. Hence, the value attributed to a particular amino acid interchange in the template is not a constant, but is dependent upon the environmental context in which that substitution has occurred. We have used these structural templates to align proteins, as well as to search an amino acid sequence data bank for proteins having a similar fold. Indeed, a database of templates that corresponds to both unique structures and aligned homologous structures from the Brookhaven Protein Data Bank has been produced. A new sequence can be searched against the database of templates in order to identify a similar tertiary fold even if the sequence is not significantly similar to any proteins of known three-dimensional structure. PMID- 8515449 TI - Nuclear magnetic resonance comparison of the binding sites of mithramycin and chromomycin on the self-complementary oligonucleotide d(ACCCGGGT)2. Evidence that the saccharide chains have a role in sequence specificity. AB - A comprehensive two-dimensional 1H nuclear magnetic resonance spectral analysis of the ternary 4:2:1 mithramycin-Mg2+-d(A1C2C3C4G5G6G7T8)2 complex and the ternary 2:1:1 chromomycin-Mg(2+)-d(A21C2C3C4C4G5G6G7T8)2 complex is presented. The self-complementary oligonucleotide is found to bind two dimers of mithramycin in two identical off-center binding sites such that the twofold symmetry of the oligonucleotide is retained. In contrast, the same oligonucleotide binds only one dimer of chromomycin in a single but distinct off-center binding site. Two dimensional nuclear Overhauser spectroscopy experiments show that the aglycone binding site of the drug dimer in each complex extends over almost four base pairs and is similar in length to other complexes between chromomycin or mithramycin and oligonucleotides. The data demonstrate that the chromomycin dimer binding site is offset by one base-pair step from the dimer binding site in the mithramycin complex. This preferred binding site prevents two dimers of chromomycin binding to d(ACCCGGGT)2 for steric reasons and lends further support to previous work that showed the 5'-CG base-pair site is less favored by these drugs compared to the 5'GC and 5'-GG,5'-CC sites. Evidence is presented that suggests mithramycin may occupy either of two distinct binding sites on d(ACCCGGGT)2 when the drug concentration is not saturating. The nuclear magnetic resonance data demonstrate that the saccharide chains of this family of drugs do have a role in determining the binding site on nucleotides and as a consequence the CDE trisaccharide chain may alter its conformation to fulfil this role. Titration of mithramycin up to a drug-duplex ratio of 7:1 reveals further association of mithramycin with the complex but no new drug-oligonucleotide nuclear Overhauser enhancement contacts. PMID- 8515450 TI - The crystal structure of the trigonal decamer C-G-A-T-C-G-6meA-T-C-G: a B-DNA helix with 10.6 base-pairs per turn. AB - The B-DNA decanucleotide C-G-A-T-C-G-6meA-T-C-G has been crystallized under the same conditions used earlier for C-G-A-T-C-G-A-T-C-G, but is found to adopt a new trigonal P3(2)21 packing mode instead of the expected orthorhombic P2(1)2(1)2(1) form. Unit cell dimensions a = b = 33.38 A, c = 98.30 A, gamma = 120 degrees, imply ten base-pairs or one complete decamer double helix per asymmetric unit. The 2282 two-sigma data to 2.0 A refine to R = 17.2% with 45 water molecules, 1.5 hexavalent hydrated magnesium complexes, and 0.5 chloride ion per asymmetric unit. Neighboring helices interlock backbone chains and major grooves, crossing at an angle of 120 degrees in a manner that yields an excellent model for a Holliday junction. Local helix parameters differ markedly in the trigonal and orthorhombic structures, with the trigonal helix exhibiting behavior closer to that expected of B-DNA in solution. The trigonal form has an average of 10.6 base pairs per turn, in contrast to 9.7 base-pairs per turn in the orthorhombic cell. A comparison of all known B-DNA decamer and dodecamer crystal structure analyses indicates that, the greater the cell volume per base-pair (and hence the more open the crystal structure), the closer the mean helix twist approaches an expected 10.6 base-pairs per turn. PMID- 8515451 TI - Structure and molecular model refinement of pig pancreatic alpha-amylase at 2.1 A resolution. AB - The previously reported structural model of porcine pancreatic alpha-amylase has been corrected and improved by a genuinely independent structure solution. The electron density map was established by multiple isomorphous replacement (m.i.r.; using 5 derivatives) and subsequent solvent-flattening at 2.8 A resolution. The sequence was built into the well-defined regions of the m.i.r. map; this partial model was refined using a simulated annealing refinement method with phase restraints. Phase combination of m.i.r. phases and phases of the partial model allowed the completion of the model. The final refinement was based on 29,838 independent reflections in the 8 to 2.1 A resolution range. A final R-factor of 15.6% was obtained with a model obeying standard geometry within 0.014 A in bond lengths and 2.8 degrees in bond angles. The final model consists of all 496 amino acid residues, 1 calcium ion, 1 chloride ion and 353 water molecules. The model is described in detail; the calcium and chloride binding sites are characterized. PMID- 8515452 TI - Nuclear magnetic resonance solution structure of the pheromone Er-10 from the ciliated protozoan Euplotes raikovi. AB - The three-dimensional structure in solution of the pheromone Er-10 from the ciliated protozoan Euplotes raikovi has been determined by nuclear magnetic resonance spectroscopy. The structure of this 38-residue protein was obtained from 384 nuclear Overhauser enhancement distance constraints and 78 dihedral angle constraints using the distance geometry program DIANA for the structure calculation and the program AMBER for energy minimization. For a group of 20 conformers used to characterize the solution conformation, the average root-mean square distance calculated for the backbone heavy atoms relative to the mean structure was 0.33 A. The structure includes three short helices of residues 2 to 8, 12 to 19 and 24 to 33, and a turn in the carboxy-terminal region of residues 34 to 38. These structural elements are held together by three disulfide bridges. The structure is quite stable relative to heat denaturation, since at both pH 4.6 and pH 6.0 only minor changes in the circular dichroism and nuclear magnetic resonance spectra were observed over the temperature range 20 to 80 degrees C. The surface of the Er-10 structure shows an asymmetric charge distribution that results in a predominantly apolar surface on one side of the molecule. There is also a deep cleft in the structure with an asymmetric distribution of charged and apolar residues on the two walls. These surface features may be important for the homologous (autocrine) and heterologous binding of the pheromone to receptors. PMID- 8515453 TI - Empirical scale of side-chain conformational entropy in protein folding. AB - A major effect in the energetics of protein folding is the loss of conformational entropy of the side-chains. The definition of entropy as the Boltzmann sampling over all states (S = -R sigma p(i) ln p(i)) requires evaluation of the probability (p(i)) of the system being in rotameric state i. The principle of this paper is to obtain an estimate of p(i) from the observed distribution of exposed side-chain rotamers in 50 non-homologous protein crystal structures. However because of limited data we show that for all side-chains except Asn, Asp and Glu the side-chain distribution is independent of burial and accordingly all data were pooled in the calculation of p(i). For Asn, Asp and Glu side-chains with relative accessibility > 60% were used. The scale includes effects due to the symmetry of side-chains such as Phe and the free rotation of side-chain amide, carboxyl and hydroxyl groups. An empirical scale for the loss of side chain conformational entropy during protein folding is thereby obtained. Values of the change in free energy due to entropy (-T delta S) on burying a side-chain range from 0 for Ala, Gly and Pro to +2.1 kcal/mol for Gln (T = 300 K). We explore the consistency of a simple model for protein folding that includes side chain entropy, main-chain entropy, hydrophobicity and hydrogen bonding. The stability of site-directed mutations is discussed in terms of conformational entropy. PMID- 8515454 TI - Configurational distribution of denatured phosphoglycerate kinase. AB - Physiochemical characterization of the denatured states of proteins is important for a complete understanding of the factors stabilizing their folded conformations. Using a combination of small angle neutron scattering (SANS), statistical mechanical modelling and molecular mechanics calculations, we examine the configurational distribution of phosphoglycerate kinase denatured in 4 M guanidine hydrochloride solution. The denaturing of the protein produces a clear change in the form of the SANS profile and a large increase of the radius of gyration. In the statistical mechanical model, the region of contrast neutron scattering density associated with the protein is pictured as a chain of freely jointed spheres. The model is fitted to the SANS data for the denatured protein. It is found that a model with a small number of spheres cannot account for the higher resolution scattering, indicating an absence of detectable structuration; a good fit is found with 100 spheres of 8.5 A radius. Single configurations of the fitted chain of spheres are used as low-resolution bounds for model-building and molecular mechanics calculations to obtain plausible atomic-detail models of the denatured chain. PMID- 8515455 TI - A method to configure protein side-chains from the main-chain trace in homology modelling. AB - Protein homology modelling typically involves the prediction of side-chain conformations in the modelled protein while assuming a main-chain trace taken from a known tertiary structure of a protein with homologous sequence. It is generally believed that the need to examine all possible combinations of side chain conformations poses the major obstacle to accurate homology modelling. Methods proposed heretofore use only discrete or limited searches of the side chain torsion angle space to mitigate the combinatorial problem and also rely on simplified energy functions for calculational speed. The configurational constraints are typically based upon use of frequently observed torsion angles, fixed steps in torsion angles, or oligopeptide segments taken from tertiary structural databanks that are similar in sequence and conformation with the target structure. In the present work, a more fundamental approach is explored for several protein structures and it is demonstrated that the combinatorial barrier in side-chain placement hardly exists. Each side-group can be configured individually in the environment of only the backbone atoms using a systematic search procedure combined with extensive local energy minimization. Tests, using the main-chain or both the main-chain and remaining side-chain atoms to calculate low energy geometries for each residue, established the dominance of the main chain contribution. The final structure is achieved by combining the individually placed side-chains followed by a full energy refinement of the structure. The prediction accuracy of the present homology modelling technique was assessed relative to other automated procedures and was found to yield improved predictions relative to the known side-chain conformations determined by X-ray crystallography. PMID- 8515456 TI - The crystal structure of tris-inhibited phospholipase C from Bacillus cereus at 1.9 A resolution. The nature of the metal ion in site 2. AB - We report here the crystal structure of the complex formed between phospholipase C (PLC) from Bacillus cereus and the widely used biochemical buffer tris (hydroxymethyl)-methylamine (Tris). The structure has been determined at 1.9 A resolution and refined to R = 20.3%. Tris has metal-binding properties, especially to Zn2+, and has been reported to reduce the activity of PLC. The amine nitrogen atom in Tris is co-ordinated to one of the three Zn2+ ions in the active site of the enzyme, thus confirming its chelating properties and the involvement of the metal ions in the catalytic process. The occupancy of the Zn2+ ion in site 2 in native PLC is 0.6 which could imply the presence of Ca2+ rather than Zn2+. The fact that Tris binds to this metal ion, the nature of the site 2 co-ordination shell and comparison with several homologous Zn-metalloenzymes indicate that PLC is a 3-Zn metalloenzyme. This study is one of a series which explores the active site of PLC by complexing the enzyme with inhibitors and substrate analogues. PMID- 8515457 TI - Crystal structure of hydrophobic protein from soybean; a member of a new cysteine rich family. AB - X-ray diffraction methods have been used to determine the structure of the 8.3 kDa hydrophobic protein from soybean and to refine the atomic co-ordinates to a crystallographic R-factor of 18.7% at 1.8 A resolution. The molecule is a four helix bundle, which together with the connecting loops and a twisted beta-strand form a spiral. The surface contains 70% apolar atoms, and the crystal packing is dominated by hydrophobic interactions, producing a two-dimensional sheet of protein molecules. Most of the 59 water molecules located are involved in hydrophilic contacts and their structural organization does not seem to be affected by the high hydrophobicity of the molecule. From the protein fold it appears that three of the four disulphide bridges are important for keeping the amino and carboxyl-terminal segments in place in the native form, while the central part of the molecule is stabilized by many hydrophobic interactions. Although the protein function is not known, a number of possibilities can be excluded on experimental grounds and by comparison with other members of the family. PMID- 8515458 TI - Common ring motifs in proteins involving asparagine or glutamine amide groups hydrogen-bonded to main-chain atoms. AB - We report the frequent occurrence in proteins of motifs consisting of either 9 membered or 11-membered rings that involve the side-chain amide groups of asparagine and glutamine residues. The syn CO and NH groups of these amide groups are hydrogen-bonded to the main-chain NH and CO groups of other amino acid residues. The main-chain part of both the 9-membered and 11-membered rings has the conformation of a beta-strand. One such ring motifs occurs, on average, in half of all the proteins we examined. Similar conformations are found for most examples of the 9-membered and 11-membered rings. One of the 11-membered rings is distinct, compared to the others, in that its main-chain part has a mirror-image conformation. Another of the 11-membered rings occurs at the interior of the variable domains of some antibodies and assists in linking the two beta-sheets. We observe one 9-membered ring structure in a dihydrofolate reductase complex in which the amide in the nicotinamide group of the ligand NADP is bound to the enzyme. Groups that can form hydrogen bonds in a similar way to amide groups occur in several nucleotide bases; we find one example of a 9-membered ring involving adenine and main-chain atoms in the FAD-protein complex of glutathione reductase. Both have conformations like those of the other 9-membered rings. PMID- 8515459 TI - Stability and folding kinetics of ribonuclease T1 are strongly altered by the replacement of cis-proline 39 with alanine. AB - The refolding of ribonuclease T1 involves two major slow processes that exhibit properties of prolyl isomerization reactions. A comparison of the wild-type protein and a designed variant where the cis Ser54-Pro55 bond was replaced by a Gly54-Asn55 bond indicated that the faster of these reactions is the isomerization of Pro55. Here we report the replacement of the other cis proline of ribonuclease T1 at position 39 by alanine. The Pro39Ala variant is similar to the wild-type protein in secondary and tertiary structure, and the enzymatic activity towards RNA and a dinucleotide substrate remains almost unchanged. The fluorescence emission of the single Trp59 is lowered by the Pro39Ala substitution, probably because Trp59 is in close contact to Pro39 in wild-type ribonuclease T1. Unlike the substitution of cis Pro55, the Pro39Ala mutation is strongly destabilizing and reduces the Gibbs free energy of the folded protein by about 20 kJ/mol. Pro39 is buried in native RNase T1 and located near the active site. The observed destabilization could originate from the presence of a cis alanyl bond in the Pro39Ala variant or from a local distortion caused by the incorporation of a trans alanyl peptide bond in the interior of the protein. In the refolding kinetics the replacement of Pro39 leads to a disappearance of the fast-refolding species. Refolding still involves two consecutive slow steps. The first and faster step could be the isomerization of the remaining cis Pro55. The second, very slow step is a novel reaction that appears to have no counterpart in the refolding of the wild-type protein. All mutant molecules must undergo this reaction before reaching the native state. These major changes in the folding kinetics strongly indicate that cis-Pro39 is indeed of major importance for the folding of the wild-type protein. They indicate, moreover, that some new feature of protein folding kinetics is observed in these studies of the Pro39Ala variant. PMID- 8515460 TI - Kinetic models for unfolding and refolding of ribonuclease T1 with substitution of cis-proline 39 by alanine. AB - The replacement of cis proline 39 of ribonuclease T1 by an alanine residue leads to a decrease in stability by about 20 kJ/mol and to major changes in the folding kinetics that are not easily explained by the proline model for protein folding. In particular, a novel very slow reaction is observed in the refolding of the Pro39Ala variant. Here the unfolding and refolding kinetics of this protein are further investigated. We show that the very slow reaction is not a prolyl isomerization. It is not created by a slow isomerization of the unfolded protein, nor is it catalyzed by prolyl isomerase, and all molecules have to undergo this reaction during refolding. Most of the unfolded Pro39Ala molecules contain an incorrect trans isomer at the remaining cis Pro55. They use a sequential pathway for refolding, in which trans to cis isomerization at Pro55 precedes the very slow reaction. The refolding of the minor fraction of unfolded Pro39Ala molecules with a correct cis isomer at proline 55 is a single first-order reaction that is limited in rate by the very slow step. The folding mechanism of wild-type ribonuclease T1 cannot be used to explain these results and independent mechanisms are proposed to model the unfolding and refolding of the Pro39Ala variant. The molecular interpretation of the changes in the folding mechanism is tied to the question, as to whether the cis character of the peptide bond at position 38-39 is maintained after the substitution of Pro39 by alanine. A possible explanation could be that the novel very slow folding reaction involves the trans to cis isomerization of the Tyr38-Ala39 bond. Such a reaction is probably slow, since the activation energy is high and since tight coupling with the formation of structure is required to stabilize the cis form of a non-prolyl peptide bond. Alternatively, the strong decrease in folding rate could be correlated with the general destabilization of ribonuclease T1 by the Pro39Ala mutation. PMID- 8515461 TI - Crystals of the phenylalanyl-tRNA synthetase from Thermus thermophilus HB8 complexed with tRNA(Phe). AB - Phenylalanyl-tRNA synthetase (EC 6.1.1.20) from the extreme thermophile Thermus thermophilus HB8 has been crystallized with its cognate tRNA. Compared with the native crystals, the crystals of the complex are more stable to radiation damage and diffract to 3.0 A resolution. They are of space group P3(2)21, with a = b = 175 A, c = 142.1 A, gamma = 120 degrees, almost identical with the crystal parameters of the native synthetase. PMID- 8515462 TI - The 5' flanking sequences of the mouse P-cadherin gene. Homologies to 5' sequences of the E-cadherin gene and identification of a first 215 base-pair intron. AB - A genomic clone containing the 5' region of the mouse P-cadherin gene has been isolated from Balb/c mice. A major feature of this genomic sequence is the presence of a first intron (Il), 215 bp long, located 48 bp downstream of the translation start ATG codon. The presence of Il has been detected both in Balb/c and C57BL/6 mouse strains, being located at the same position with respect to coding sequences as in the mouse E-cadherin and chicken L-CAM genes. The transcription initiation site of the mouse P-cadherin gene has been located at about 68 nt from the ATG start codon, giving an estimation for the size of the first exon of the mouse P-cadherin gene of 116 bp. The sequence of the 5' upstream region of the P-cadherin gene presents structural similarities with the recently described 5' region of the mouse E-cadherin gene: absence of a TATA box, presence of a CAAT box at -65, two putative AP2-binding motifs, at -101 and +31, and a GC-rich region containing a potential SP1-binding element at -88. However, no sequence homologous to the palindromic sequence, E-pal, found on the E cadherin promoter has been found in the 5' region of the P-cadherin gene. These results indicate that, in contrast to a previous report, the mouse E and P cadherin genes exhibit a similar genomic organization both containing 15 introns and a similar size for the first two exons. PMID- 8515463 TI - A DNA dodecamer containing an adenine tract crystallizes in a unique lattice and exhibits a new bend. AB - The structure of d(CGCGAAAAAACG)/d(CGTTTTTTCGCG) was determined at 2.3 A resolution in order to deduce the local structural features that give rise to DNA bending by adenine tracts. Whereas all previously reported B-DNA dodecamers have crystallized isomorphously (spacegroup P2(1)2(1)2(1) with unit cell dimensions of a = 24.5 A, b = 40.3 A, c = 65.9 A), the duplex reported here crystallizes in a different lattice (spacegroup P2(1)2(1)2 with unit cell dimensions of a = 44.8 A, b = 66.1 A, c = 42.9 A). The DNA exhibits a 30 degree bend in the helix axis that is 180 degrees away from the 20 degree bend exhibited by the adenine tract DNA crystal structures that have been previously determined. This bend is 90 degrees away from the bend predicted for an adenine tract by solution and gel experiments. The adenine tract is straight and bending occurs in the G+C-rich regions. Comparison of the various adenine tract DNA crystal structures reveals that in all cases the adenine tracts have nearly identical structures, even though the overall bends of the helix axes are quite different. This implies that the structure of the adenine tract is robust, at least under the conditions of crystallization. The base-pairs in the adenine tracts exhibit a large propeller twist that leads to the formation of bifurcated hydrogen bonds and a narrow minor groove. In the crystal structure of d(CGCGAAAAAACG)/d(CGTTTTTTCGCG), a minor groove spine of hydration is observed that probably stabilizes the straight structure of the adenine tract. This straight structure of the A-tract is not consistent with the results of fiber diffraction, gel experiments, and NMR studies. Although this may imply that the results of solution experiments need to be reinterpreted, the conditions under which the crystals were grown are different from those under which the solution experiments were done. The possibility remains that the 2-methyl-2,4-pentanediol necessary for crystal growth may facilitate formation of the spine of hydration that stabilizes the straight A-tract, although recent NMR results show the presence of the spine of hydration in aqueous solution. We have also extended our previously reported observation that non-self-complementary DNA structures can exist in the crystal lattice in two orientations. A dodecamer brominated on one strand provides experimental evidence that d(CGCAAAAAAGCG)/d(CGCTTTTTTG CG) is positioned in two orientations in the crystal lattice that are related by a 180 degree rotation around the pseudo-dyad axis of the sequence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8515464 TI - Main-chain bond lengths and bond angles in protein structures. AB - The main-chain bond lengths and bond angles of protein structures are analysed as a function of resolution. Neither the means nor standard deviations of these parameters show any correlation with resolution over the resolution range investigated. This is as might be expected as bond lengths and bond angles are likely to be heavily influenced by the geometrical restraints applied during structure refinement. The size of this influence is then investigated by performing an analysis of variance on the mean values across the five most commonly used refinement methods. The differences in means are found to be highly statistically significant, suggesting that the different target values used by the different methods leave their imprint on the structures they refine. This has implications concerning the actual target values used during refinement and stresses the importance of the values being not only accurate but also consistent from one refinement method to another. PMID- 8515465 TI - Mapping of the zinc binding domain of Escherichia coli methionyl-tRNA synthetase. AB - Cys/His motifs, found in several nucleic acid binding proteins, generally correspond to sites for the binding of metal atoms. Such a motif, comprising four Cys residues, occurs in the subunits of Escherichia coli methionyl-tRNA synthetase, a dimeric enzyme known to bind two zinc atoms. In this study, each of the four cysteines in the cysteine cluster (region 145 to 161) of E. coli methionyl-tRNA synthetase were successively changed into an alanine. Either substitution is sufficient to destabilize the tight binding of the zinc ion. Moreover, a peptide having a sequence corresponding to that of the 138 to 163 region of methionyl-tRNA synthetase has been prepared. It strongly binds one zinc atom, even in the presence of ethylene diamine tetraacetate. These data establish that, in methionyl-tRNA synthetase, the Cys motif of region 145 to 161 is actually the binding site for zinc. In addition, the mutation of each cysteine modifies the parameters of the methionine activation reaction, and appears to change the structure of the enzyme, as probed by an increased sensitivity of the mutant enzymes to trypsin attack. The possible role of the zinc atom and of its chelating residues in the folding of the active centre of methionyl-tRNA synthetase is discussed. PMID- 8515466 TI - Methionyl-tRNA synthetase zinc binding domain. Three-dimensional structure and homology with rubredoxin and gag retroviral proteins. AB - Methionyl-tRNA synthetase from Escherichia coli contains one tightly bound zinc atom per subunit. The region encompassing residues 138 to 163 of this enzyme is responsible for the metal binding. A 28-mer peptide corresponding to these residues was expressed in vivo and shown to contain approximately 1 mol of tightly bound Zn/mol of peptide. In this study, the three-dimensional solution structure of this peptide was solved by means of two-dimensional proton NMR spectroscopy. A total of 133 nuclear Overhauser effect distance constraints and 22 dihedral angle restraints were used for the calculations, using a hybrid distance-geometry-simulated annealing strategy. Excluding the first four residues, the resulting structure is well-defined (r.m.s.d. 0.71 A for backbone atoms) and composed of a series of four tight turns. The second and the fourth turns are composed of CXXC sequences which are structurally homologous to the NH S turns found in the metal binding sites of gag retroviral proteins and rubredoxin. The solution structure of the zinc binding peptide shows significant discrepancies with the crystal structure of methionyl-tRNA synthetase. PMID- 8515467 TI - Structural polymorphism of homopurine-homopyrimidine sequences at neutral pH. AB - Under superhelical strain and mildly acidic pH, polyd(GA).polyd(CT) sequences are known to adopt an H-y3 conformer of H-DNA. We studied the effects of the sequence length, metal ions, and pH on the structures formed by polyd(GA).polyd(CT) sequences in supercoiled plasmid DNA at bacterial superhelicity. The results from experiments that distinguish multiple structures forming in a given plasmid DNA population strongly suggest that polyd(GA).polyd(CT) sequences of 33 base-pairs or more can adopt both H-y3 and H-y5 isomeric forms of H-DNA at neutral pH either with or without magnesium ions. At pH 5 in the presence of zinc ions, H-DNA is formed. However, at pH 7 in the presence of zinc ions, polyd(GA).polyd(CT) sequences form an intramolecular d(GA).d(GA).d(CT) triplex similar to a dG.dG.dC triplex, which is stabilized with magnesium ions for poly(dG).poly(dC) sequences. Zinc ions also stabilize the dG.dG.dC triplex for relatively long poly(dG).poly(dC) sequences (more than 24 base-pairs at pH 7). PMID- 8515468 TI - Crystallization and preliminary crystallographic analysis of Escherichia coli DNA photolyase. AB - DNA photolyase from Escherichia coli (M(r) 54,000) consists of a polypeptide chain of 471 amino acids and the non-covalently bound cofactors methenyltetrahydrofolate (MTHF) and flavin adenine dinucleotide (FADH2). Two crystal forms of the enzyme were obtained; both have symmetry of space group P1. Form I has the unit cell dimensions a = 89.4 A, b = 97.3 A, c = 62.1 A, alpha = 108.3 degrees, beta = 97.4 degrees and gamma = 90.0 degrees. Diffraction from this form extends beyond 3 A resolution, but the crystals are radiation-sensitive and difficult to reproduce. Form II has the unit cell dimensions a = 62.6 A, b = 72.2 A, c = 58.5 A, alpha = 99.1 degrees, beta = 101.5 degrees and gamma = 72.0 degrees; most likely, the unit cell contains two molecules. High diffraction quality and reproducibility make form II suitable for structure analysis. PMID- 8515469 TI - Crystallization and preliminary X-ray diffraction studies of Theiler's virus (GDVII strain). AB - Theiler's murine encephalomyelitis virus (TMEV) is a member of the picornavirus family. Mice infected with TMEV serve as models for the study of human neurological diseases including multiple sclerosis. Preparations of the GDVII strain of Theiler's virus have been crystallized using the hanging drop technique. When exposed to high intensity synchrotron radiation, these monoclinic crystals diffracted X-rays to at least 3.0 A resolution. The unit cell has a C centered lattice with dimensions: a = 575.2 A, b = 324.0 A and c = 558.4 A, beta = 108.2 degrees. The molecular mass and cell dimensions imply that there is an entire virus particle per asymmetric unit, suggesting the presence of 60-fold non crystallographic redundancy. This GDVII crystal form appears to be suitable for high-resolution structure determination. PMID- 8515470 TI - Crystallization and preliminary X-ray data for the A-isozyme of O-acetylserine sulfhydrylase from Salmonella typhimurium. AB - The A-isozyme of O-acetylserine sulfhydrylase, a pyridoxal phosphate-dependent enzyme isolated from Salmonella typhimurium catalyzes the synthesis of L-cysteine from O-acetyl-L-serine and sulfide. The pyridoxal form of the enzyme has been crystallized in two different forms. One form is in the orthorhombic space group P2(1)2(1)2(1) with cell constants a = 144.4 A, b = 96.9 A and c = 54.3 A and contains two monomers each of molecular weight 34,000 per asymmetric unit. The second form is in a hexagonal space group with unit cell dimensions a = b = 115 A, and c = 348 A and contains two 68,000 dimers per asymmetric unit. Complete native enzyme data sets have been collected for both crystal forms using an R Axis II detector. A search for suitable heavy-atom derivatives is underway. Although both crystal forms diffract X-rays to better than 2.5 A, the orthorhombic form is more suited to a detailed structural analysis due to the extended lifetime in the X-ray beam and the relative size of the unit cell. PMID- 8515471 TI - Crystals of human growth hormone-receptor complexes. Extracellular domains of the growth hormone and prolactin receptors and a hormone mutant designed to prevent receptor dimerization. AB - A single-site human growth hormone mutant (hGH[G120R]), which inhibits receptor dimerization, was used to produce single crystals, suitable for high-resolution diffraction studies, of 1:1 complexes with the ligand-binding domain of the growth hormone receptor (hGHbp) and of the prolactin receptor (hPRLbp). Crystals of the hGH[G120R]-hGHbp complex are in space group P4(1)2(1)2 or P4(3)2(1)2 with a = 67.7 A, c = 228.0 A, and diffract to at least 2.2 A. Crystals of the complex between hGH[G120R] and hPRLbp are in space group P2(1)2(1)2 with a = 154.0 A, b = 68.4 A, c = 42.9 A, and diffract to at least 2.8 A. The structures of these two complexes will shed light on the early events in receptor activation, and provide the basis for an analysis of receptor specificity of growth hormone and prolactin. PMID- 8515472 TI - Crystallization and preliminary crystallographic analysis of antistasin, a leech derived inhibitor of blood coagulation factor Xa. AB - The salivary gland of the Mexican leech Haementeria officinalis contains a 15 kDa protein which is a potent and selective inhibitor of factor Xa. It inhibits not only blood coagulation, but also metastasis. A gene, coding for a sequence similar to published antistasin sequences, has been synthesized and expressed in Chinese hamster ovary (CHO) cells. The recombinant protein was purified and crystallized at pH 6.0, using 31% ammonium sulfate as a precipitant. The crystals diffract at least to 2.8 A. The spacegroup is I422 with a = b = 77.7 A and c = 88.4 A. The crystals contain 42% solvent and one protein molecule in the asymmetric unit. A search for heavy atom derivatives is in progress. PMID- 8515473 TI - Crystallization and preliminary X-ray investigation of recombinant simian immunodeficiency virus proteinase. AB - Simian immunodeficiency virus (SIV) proteinase has been crystallized from sodium acetate buffer with sodium chloride as precipitant. The crystals are orthorhombic and the space group is C222(1) with unit cell dimensions a = 32.18 A, b = 62.52 A, c = 95.76 A, alpha = beta = gamma = 90 degrees, indicating a single monomer of 10 kDa in the asymmetric unit. The crystals grow to dimensions of 0.2 mm x 0.2 mm x 0.07 mm within a week and are stable in the X-ray beam for at least 50 hours. A different crystal lattice was observed for SIV proteinase crystallized in the presence of pepstatin. The space group was P2(1)2(1)2(1) with cell dimensions of a = 35.26 A, b = 58.59 A, c = 93.95 A, alpha = beta = gamma = 90 degrees. Diffraction beyond 1.7 A was observed, indicating that a high resolution structure analysis is feasible. PMID- 8515474 TI - Redox regulation of in vitro DNA-binding activity by the homeodomain of the Isl-1 protein. AB - The rat Isl-1 gene encodes a protein involved in transcriptional regulation. This protein contains two copies of the cysteine-rich motif LIM domain in addition to a DNA-binding homeodomain. Chemical modification of the free sulphydryl group of a single cysteine residue at position 54 in the homeodomain can both stimulate and inhibit DNA-binding in vitro. Oxidation prevented DNA binding by the homeodomain but had no effect if the homeodomain was first bound to DNA. Replacement of this cysteine residue with serine abrogated sensitivity to oxidation-reduction changes and increased the DNA-binding activity of the homeodomain. These in vitro results suggest that transcriptional regulation through the Isl-1 protein might be modulated by the intracellular redox environment. PMID- 8515475 TI - Factors influencing the repair of the mutagenic lesion O6-methylguanine in DNA by human O6-methylguanine-DNA methyltransferase. AB - Oligodeoxynucleotides of various chain lengths (p(Bp)nB, n < or = 9) and the eight possible dinucleotide phosphates (pm6GpB and pBpm6G), each containing a single O6-methylguanine residue (m6G), were used to study the repair kinetics of this lesion by the cloned DNA repair proteins; human 21 kDa O6-methylguanine-DNA methyltransferase (MGMT), human 43 kDa glutathione-S-transferase fused MGMT (GSTMGMT) and the Escherichia coli 39 kDa ada protein. The observed second-order repair rate constants are dependent upon both the chain length of the oligonucleotide substrates for all three proteins and in the case assuming O6 methylguanine is similar to B). The differences observed in the ratios of the rate constants for the substrates with five and four base residues; 125 for the E. coli 39 kDa ada protein, 640 for the human MGMT and 27,800 for the human fusion protein GSTMGMT, suggest that the pentanucleotide phosphate containing this lesion is the "optimal" substrate for the proteins. Surprisingly, the human GSTMGMT is shown to be more effective in the repair of longer substrates with the second-order repair rate constants for TATA-Cm6GTATA being 6.16 x 10(6) for GSTMGMT, 2.00 x 10(6) for MGMT and 0.27 x 10(6) M-1 s-1 for the E. coli 39 kDa ada protein. Thus, the presence of an additional protein domain at the N terminus of human MGMT can alter its selectivity towards certain substrates. Although a number of peptide domains are conserved between the E. coli 39 kDa ada protein and phosphates can also be used to explain the observed sequence specific repair of this lesion within certain DNA sequences. PMID- 8515477 TI - Reversible pressure dissociation of R17 bacteriophage. The physical individuality of virus particles. AB - In the absence of urea, pressures up to 2.5 kbar promote only 10% dissociation of the whole particles of R17 bacteriophage. In the presence of concentrations of urea between 1.0 and 5.0 M, pressure promotes complete, reversible dissociation of the virus particles. At the lower urea concentrations reversible dissociation of R17 virus particles shows no dependence on protein concentration indicating a high degree of heterogeneity of the particles, but higher urea concentrations, 2.5 to 5.0 M, result in progressive restoration of the protein concentration dependence of the pressure dissociation. At still higher urea concentrations, 5.0 to 8.0 M, irreversible dissociation of virus takes place at atmospheric pressure. In contrast, the dissociation of the isolated dimers of the capsid protein was dependent on protein concentration to the extent predicted for a stochastic equilibrium, and dimers were much less stable than the whole virus both to dissociation by pressure or urea. In contradistinction, the reversible whole virus dissociation observed at urea concentrations below 2.5 M appears to be a typical deterministic equilibrium, without appreciable dynamic exchange between whole particle and subunits during the lengthy experiments. The experiments demonstrate that the "thermodynamic individuality" of the virus particles arises in conformational differences in the assembled viruses, and that there is a direct relation between the stability of the particles and their heterogeneity. PMID- 8515476 TI - Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway. AB - We have identified a family of abundant acidic human keratinocyte proteins with apparent molecular masses ranging between 30,000 and 31,100 (isoelectric focussing sample spot proteins 9109 (epithelial marker stratifin), 9124, 9125, 9126 and 9231 in the master two-dimensional gel database of human keratinocyte proteins) that share peptide sequences with each other, with protein 14-3-3 and with the kinase C inhibitory protein. Immunofluorescence staining of keratinocytes showed that two of these proteins (IEF SSPs 9124 and 9126) localize to the Golgi apparatus, while stratifin is distributed diffusely in the cytoplasm. Significant levels of stratifin, and in smaller amount the sample spot proteins 9124, 9125 and 9126, were detected in the medium of cultured human keratinocytes suggesting that they are partially secreted by these cells. Two dimensional gel analysis of proteins from cultured human cells and fetal tissues showed that polypeptides comigrating with proteins 9124, 9125 and 9126 are ubiquitous and highly expressed in the brain. Stratifin, however, was present only in cultured epithelial cells and was most abundant in fetal and adult human tissues enriched in stratified squamous keratinising epithelium. We have cloned and sequenced cDNAs coding for members of this family. The complete identity of the sequenced peptides from stratifin with the amino acid sequence translated from the stratifin cDNA clone indicated that this cDNA codes for stratifin. The identity of clones 1054, HS1 and AS1 is less clear as, with few exceptions, none of the individual peptide sequences fits the predicted protein sequences. The polypeptides synthesized by clones 1054 and HS1 in the vaccinia expression system, on the other hand, comigrate with proteins 9126 and 9124, suggesting cell type-specific expression of members of the protein family. Database searches indicated that clone HS1 corresponds to a human T-cell cDNA 14-3-3 clone, while the high level of similarity of clones 1054 and AS1 with the 14-3-3 beta and eta sequences respectively, suggested that they code for the human equivalent of the two bovine proteins. Microsequence data indicated that IEF SSP 9124 corresponds to the human homolog of bovine 14-3-3 gamma. PMID- 8515478 TI - Chiropteran tendon locking mechanism. AB - Rather than the usual mammalian scheme in which tendon and sheath surfaces provide as little friction as possible, the tendons and sheaths of many bats have a locking segment on the manual and pedal flexor tendon complex. This tendon locking mechanism (TLM) exists opposite the proximal phalanges of each toe and pollex of many bats. Its structure, similar to a ratchet mechanism, assists bats in hanging with little muscular effort. The third digit of the pelvic limb and the pollex of species representing 15 chiropteran families were studied to determine the presence or absence, morphology, and function of the TLM. Most of the species studied have a TLM consisting of a patch of tubercles on the ventral surface of the flexor tendon associated with the proximal phalanx of each pollex or toe. The sheath adjacent to this portion of the flexor tendon has a series of transverse folds or ridges, which, when engaged with the tubercles on the tendon, lock the tendon in place. The TLM is similar in megachiropterans and microchiropterans possessing it. The TLM is absent, however, in some of the microchiropterans studied, most notably in the phyllostomids. Since many birds have a TLM similar to that of bats, it is an excellent example of the convergent evolution of a feature brought about by similar functional pressures on birds and bats. PMID- 8515479 TI - Early events in myofibrillogenesis and innervation of skeletal, sound-generating muscle in a teleost fish. AB - The plainfin midshipman, Porichthys notatus, generates acoustic communication signals through the rapid contraction of a pair of vocal (sonic) muscles attached to the walls of the swimbladder. Light and electron microscopic methods were used to study two aspects of sonic muscle ontogeny: 1) the development and transformation of myotubes into muscle fibers and 2) innervation, including the formation of sonic neuromuscular junctions and the myelination of sonic motor axons. Sonic motor axons are associated with sonic mesenchyme during its initial migration away from occipital somites. However, myofibrillogenesis, the formation of neuromuscular junctions, and axon myelination do not occur until sonic mesenchyme reaches its final destination (i.e., the swimbladder). A continuum of developing myotubes is present rather than two temporally distinct populations of primary and secondary myotubes as observed for skeletal muscles in mammalian and avian species. Potential reasons for the lack of primary and secondary myotubes are considered, including the functional homogeneity of the sonic motor system and the sonic muscle's unique architecture, namely its direct attachment to the wall of the swimbladder. PMID- 8515480 TI - Screening for cervical cancer: prospects for the future. PMID- 8515481 TI - Clonality: more than just a tumor-progression model. PMID- 8515482 TI - New EC privacy directive worries European epidemiologists. PMID- 8515484 TI - Gene therapy OK'd for pediatric brain tumors. PMID- 8515485 TI - International consensus: high-dose chemo with BMT is not standard treatment. PMID- 8515483 TI - Brain tumor incidence rising; researchers ask why. PMID- 8515486 TI - IARC publishes data on worldwide cancer cases. International Agency for Research on Cancer. PMID- 8515488 TI - The cutting edge for cancer information is interactive. PMID- 8515487 TI - Radioactive bullets raise cancer fears. PMID- 8515489 TI - The challenge for leadership in the national agenda for relief of cancer pain. PMID- 8515491 TI - Detection of preinvasive cancer of the cervix and the subsequent reduction in invasive cancer. AB - BACKGROUND: Cytologic screening and follow-up can reduce the incidence of cervical cancer by detection and removal of precursor lesions. It is unknown, however, whether differences in histopathologic criteria for these precursor lesions affect the benefit of screening. These criteria may be difficult to study, but they are likely to be reflected in reported incidence of in situ cancer in small areas of Sweden. PURPOSE: Our purpose was to test the hypothesis that the benefit of screening can be predicted by histopathologic criteria as reflected in the reported incidence of cancer in situ. METHODS: Incidence data were from the Swedish National Cancer Registry. Regression models showing the relationship between in situ and invasive cancer were formulated and estimated. Each county (total, 24) was a unit of measurement, and adjustment was made for the incidence of invasive cancer before screening. RESULTS: During population based screening in Sweden, the incidence of cancer in situ varied about fourfold among the 24 counties, which indicates that the criteria used to diagnose cancer in situ differed markedly. No statistically significant (P < .05) associations were found between the incidence of cancer in situ in 1965, 1970, or 1975 and the reduction in invasive cancer 5, 10, or 15 years later. According to the best fitting model, detection of 100 extra cases of cancer in situ per 100,000 women per year in 1975 resulted in a reduction of 1.0 (95% confidence interval [CI] = 1.6-3.7) cases of invasive cancer 10 years later. The corresponding best model estimate implied a reduction of 4.6 cases (95% CI = 1.5-7.7) in a model restricted to cancer in situ in patients aged 20-50 years (when organized screening took place), invasive cancer in patients aged 30-60 years, and cancer in situ measured in 1970. CONCLUSIONS: The absent, or at most weak, association between detection of cancer in situ and subsequent reduction in invasive cancer indicates that relaxed histopathologic criteria for cancer in situ may result in extensive, unnecessary treatment of lesions that would regress spontaneously. IMPLICATION: Further studies are urgently needed to enable identification of neoplasms likely to progress to invasive, fatal disease. PMID- 8515490 TI - Tea and cancer. AB - Tea is one of the most popular beverages consumed worldwide. The relationship between tea consumption and human cancer incidence is an important concern. This topic has been studied in different populations by many investigators, but no clear-cut conclusion can be drawn. Whereas some studies have shown a protective effect of tea consumption against certain types of cancers, other studies have indicated an opposite effect. Our purpose is to provide a critical review of this topic, covering basic chemistry and biochemical activity of tea, epidemiologic investigations, and laboratory studies, as well as possible directions for future research. Studies have demonstrated either a lack of association between tea consumption and cancer incidence at specific organ sites or inconsistent results. On the other hand, many laboratory studies have demonstrated inhibitory effects of tea preparations and tea polyphenols against tumor formation and growth. This inhibitory activity is believed to be mainly due to the antioxidative and possible antiproliferative effects of polyphenolic compounds in green and black tea. These polyphenolics may also inhibit carcinogenesis by blocking the endogenous formation of N-nitroso compounds, suppressing the activation of carcinogens, and trapping of genotoxic agents. The effect of tea consumption on cancer is likely to depend on the causative factors of the specific cancer. Therefore, a protective effect observed on a certain cancer with a specific population may not be observable with a cancer of a different etiology. On the basis of this concept, we suggest future laboratory and epidemiologic studies to elucidate the relationship between tea consumption and human cancer risk. PMID- 8515493 TI - Influence of death certificate errors on cancer mortality trends. AB - BACKGROUND: Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. PURPOSE: Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. METHODS: Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. RESULTS: Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. CONCLUSIONS: The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. IMPLICATIONS: The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning. PMID- 8515492 TI - Genetic heterogeneity of the c-K-ras locus in colorectal adenomas but not in adenocarcinomas. AB - BACKGROUND: Previous molecular genetics studies of colorectal cancer have identified multiple mutations in the c-K-ras gene (also known as KRAS2) in all phases of its development. Because of technical difficulty, prior studies rarely focused attention on the detailed distribution of c-K-ras mutations in multiple regions of the same primary tumor specimen. However, with recent development of the selective UV radiation fractionation method, characterization of c-K-ras mutations in multiple regions of the same primary tumor specimen can be performed. PURPOSE: Our purpose was to describe how c-K-ras mutations were distributed among cells obtained from multiple regions of the same primary tumor in an attempt to describe differences between early and late colorectal carcinogenesis. METHODS: Formalin-fixed, paraffin-embedded tissue blocks were obtained. Seven adenocarcinomas and seven adenomas were selected for the presence of mutant c-K-ras genes and histologic transitions between normal and neoplastic tissue. Tissue sections were prepared for analysis by the selective UV radiation fractionation method by placing thin, fixed tissue sections on a plastic slide with no coverslip. Under the microscope, small ink dots from a felt-tip pen were manually placed directly on relatively pure cell subpopulations. The slides were placed with the tissue side exposed to a UV transilluminator for 2-4 hours to inactivate the DNA present in the unprotected ("undotted") cells. Individual dots were cut out of the plastic slide into 2 x 2-mm squares and placed into microfuge tubes. The DNA was extracted and supernatant used for polymerase chain reaction (PCR) analysis. Mutations at c-K-ras codons 12 and 13 were detected. RESULTS: The selective UV radiation fractionation method and PCR analysis revealed that c-K ras mutations never extended into normal mucosa and were present in all neoplastic cells regardless of phenotypes in all seven adenocarcinomas and three of the seven adenomas. Further examination of two carcinomas for p53 (also known as TP53) mutations or loss of heterozygosity demonstrated that these additional mutations were also present in all tumor cells, suggesting that a single transformed clone was responsible for the majority of growth. However, in four other adenomas, tumor heterogeneity was demonstrated, since c-K-ras mutations were detected only in discrete portions. CONCLUSIONS: Adenoma formation may include a stage in which multiple and genetically distinct neoplastic clones are present, while most carcinomas appear to have a homogeneous composition that may result from the successful progression of one of these clones. PMID- 8515494 TI - Mammography adherence and psychological distress among women at risk for breast cancer. AB - BACKGROUND: Previous studies estimate that first-degree relatives of women with breast cancer have a twofold to 10-fold increased risk of developing breast cancer. Recently, attention has focused on the mammography screening practices of women who are at high risk for breast cancer. PURPOSE: Our purpose was to characterize mammography screening practices in a sample of first-degree relatives of breast cancer patients and to identify variables that may serve as barriers to or facilitators of adherence to mammography. METHODS: Cross-sectional (rather than prospective) data were collected by telephone interviews with 140 women aged 35-79 years who had a family history of breast cancer in at least one first-degree relative (mother, sister, or daughter). Data were recorded on mammography screening patterns, depression, stress impact, and breast cancer worries. RESULTS: Women whose mammography history adhered to age-specific recommendations varied by age: 76% of first-degree relatives aged 35-39 years, 86% aged 40-49 years, and 63% aged 50 years or more. In bivariate analyses, level of education (P = .001), employment (P = .046), and time since diagnosis of the index patient (P = .044) were significantly and positively associated with mammography adherence. Variables associated negatively with adherence included age (P = .019), intrusive thoughts about breast cancer (P = .042), and breast cancer worries that interfered with daily functioning (P = .004). Multivariate analysis by logistic regression indicated that only breast cancer worries (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.09-5.9) and education (OR = 4.8; CI = 1.6-14.3) were significant independent predictors of mammography adherence. CONCLUSIONS: This study suggests that most women at high risk for breast cancer adhere to the recommended mammography screening guidelines of the National Cancer Institute. However, rates of adherence among high-risk women aged 50 years and older are suboptimal; only 63% of these women received annual screening mammograms, and 13% had never been screened. Breast cancer worries may pose a barrier to mammography adherence among high-risk women, particularly those with less formal education. IMPLICATIONS: Prospective longitudinal studies are needed to validate the present findings and to evaluate the impact of psychoeducational interventions for women with affected first-degree relatives. PMID- 8515496 TI - Brief weekly chemotherapy for elderly patients with intermediate-grade or high grade non-Hodgkin's lymphoma. PMID- 8515495 TI - Randomized trial of high-dose chemotherapy with autologous bone marrow support as adjuvant therapy for high-risk, multi-node-positive malignant melanoma. AB - BACKGROUND: Chemotherapy adjuvant to surgery in metastatic melanoma has been evaluated in only a few prospective randomized trials. In the treatment of metastatic melanoma, dacarbazine has response rates of 15%-25% and in several studies, when combined with other alkylating agents, has yielded even higher response rates. Among the highest response rates are those achieved by using high dose chemotherapy regimens combined with autologous bone marrow support (transplantation). PURPOSE: We conducted a prospective randomized clinical trial to test the efficacy of high-dose alkylating agents in combination with autologous bone marrow support given as adjuvant therapy for high-risk stage II (World Health Organization) melanoma. METHODS: Thirty-nine patients with metastases involving five or more lymph nodes were randomly assigned to one of two treatment arms within 8 weeks of lymphadenectomy: immediate treatment or observation only. The immediate-treatment arm consisted of 19 patients who, immediately after random assignment, received high-dose chemotherapy with alkylating agents, followed 3 days later by reinfusion of autologous bone marrow. The observation arm consisted of 20 patients who were observed until relapse (confirmed by biopsy) and were then treated with the identical high-dose alkylating agent chemotherapy followed by reinfusion of autologous bone marrow. Bone marrow was harvested from the patients under general anesthesia 1-2 weeks prior to chemotherapy and was cryopreserved. Chemotherapy consisted of intravenous administration of cyclophosphamide (1875 mg/m2 as a 1-hour infusion daily for 3 days), cisplatin (55 mg/m2 per day by continuous infusion over the same 72-hour period), and carmustine (BCNU) (600 mg/m2) given immediately after cisplatin on the 4th day as a 2-hour infusion. The total doses of the three drugs were 5625, 165, and 600 mg/m2, respectively. All patients received medical evaluations every 6-12 weeks over the study period. Kaplan-Meier estimates were used to determine the time to disease progression on the basis of intent to treat. RESULTS: There was no statistically significant difference in overall survival or in time to disease progression between the two treatment arms. However, the median time to progression was 16 weeks in the observation arm and 35 weeks in the immediate-treatment arm. CONCLUSIONS: Immediate adjuvant high dose chemotherapy with alkylating agents followed by autologous bone marrow support more than doubled the time to disease progression compared with observation alone, though the difference was not statistically significant. No differences in overall survival were noted. PMID- 8515497 TI - Bladder cancer in a 39-year-old female pharmacist. PMID- 8515498 TI - [Thirteen-week repeated dose toxicity by oral administration of trandolapril (RU44570) with 4-week recovery test in beagles]. AB - Trandolapril (RU44570) was orally administered to dogs at a daily dose of 2.5, 25 or 250 mg/kg for 13 weeks. After the administration period, 25 and 250 mg/kg groups were observed for recovery for 4 weeks. The results obtained are as follows: 1. One male in the 250 mg/kg group showed decrease of food consumption and body weight, stomatitis, hematemesis, decumbence, hypothermia, and finally loss of reactivity to stimuli. This animal was killed because of these severe changes on the 39th day of administration. Among the surviving animals, a temporary loss of body weight was observed in a few animals of the 25 and 250 mg/kg groups, and a decreased food consumption was sporadically seen in a few animals of the 250 mg/kg group during the administration period. No abnormal changes were found in the clinical observation and water intake in the surviving animals. 2. The changes attributable to the pharmacological effect of RU44570 were a decreased activity of the angiotensin-converting enzyme, increases in plasma renin activity and urine volume, and decreases in specific gravity and concentrations of Na, K and Cl in the urine of every administration group. A decrease in blood pressure and an increase in the PAS and Bowie positive granules in the juxtaglomerular cells were also found in the 25 and 250 mg/kg groups. In addition, thickening of the afferent arteriolar wall of the glomeruli, a basophilic change of the renal tubular epithelial cells, and localized atrophy and hypertrophy of the renal tubules were observed in the 25 and 250 mg/kg groups, and increases in BUN, ALP and creatinine, and a slight dilation of the renal tubules were seen in the 250 mg/kg group. These observations indicated that RU44570 affected renal structure at a dose of 25 mg/kg or more renal function at a dose of 250 mg/kg. The animal killed in a moribund state showed nephrosis which consisted mainly of a moderate dilation of the renal tubules and vacuolation of the renal tubular epithelial cells, stomatitis, severe hemorrhage and necrosis with neutrophil infiltration in the fundus of the glandular stomach, atrophy of the hemopoietic system, and ectopic calcification in the heart, kidneys, stomach, trachea and alveolar wall. Changes in the kidneys similar to those observed in other animals were also detected. These changes suggested that this animal lapsed into a moribund state due to renal dysfunction and the resultant uremia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8515499 TI - [Teratological study of trandolapril (RU44570) in rats]. AB - A teratogenicity study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day from day 7 to day 17 of pregnancy. In each group, 24 or 25 female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses, and 14 or 15 female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to administration of RU44570 were not observed in the dams (P). Body weight gain and food consumption were slightly depressed in the 300 mg/kg dosage group comparing with those of control group. However, RU44570 showed no adverse effect on the fetal mortality, prenatal development or teratogenicity of the fetuses. Incidence of dilatation of renal pelvis was slightly increased in fetuses in the 300 mg/kg dosage group comparing with that of the control group. However, the offspring in each treated group showed similar incidence of this abnormality to that of the control group in more advanced age. Therefore, these changes were considered to be reversible. No adverse effects on the postnatal development of the offspring containing reproductive ability were detected. The results suggest that non-effective dose level of RU44570 is 30 mg/kg for dams, 30 mg/kg for fetuses and 300 mg/kg for development in offspring, respectively. PMID- 8515500 TI - [Perinatal and postnatal study of trandolapril (RU44570) in rats]. AB - A perinatal and postnatal study was performed in female Sprague-Dawley rats treated orally with trandolapril (RU44570) at dosage levels of 3, 30 and 300 mg/kg/day from day 17 of pregnancy to postpartum day 21. In each group, 24 or 25 pregnant female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to the administration of RU44570 were not observed in the dams (P). In the 30 and 300 mg/kg group, food consumption was slightly lower than that of the control group during the lactation period, however RU44570 did not affect body weight gain. Incidence of dilatation of renal pelvis with higher value in kidney weight was increased in offspring (F1) in the 30 and 300 mg/kg dosage groups, and water consumption at the same dosage groups was higher than that of the control group. Body weight gain in offspring (F1) was depressed in each treated group and viability of offspring (F1) from postpartum day 0 to day 4 was slightly decreased in the 30 and 300 mg/kg dosage groups comparing with that of the control group. No adverse effects were observed on the other postnatal development of the offspring, such as differentiation, sexual maturation, reflex, motor activity, emotionality, learning ability and reproductive performance. No adverse effects were detected in the second generation offspring (F2). The results suggest that the non-effective dose of RU44570 is 3 mg/kg for dams (P), lower than 3 mg/kg for development in offspring and 300 mg for fetuses (F2), respectively. PMID- 8515501 TI - [Antigenicity study of trandolapril (RU44570)]. AB - Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study. PMID- 8515502 TI - [Reverse mutation test of trandolapril (RU44570) with bacteria]. AB - Mutagenicity of trandolapril (RU44570) was evaluated by the reverse mutation test with bacteria (test strains used: Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2uvrA). The test was conducted by the preincubation method without metabolic activation (in the absence of S9 mix) and with metabolic activation (in the presence of S9 mix). The number of revertant colonies in the bacterial strains did not exceed twice that obtained in the solvent control either in the presence or absence of S9 mix. There was no dose-dependent increase in the number of revertant colonies observed. Based on the above results, it is concluded that RU44570 has no mutagenicity (gene mutation) under the conditions of the present study. PMID- 8515503 TI - [Twelve-month oral toxicity study of trandolapril (RU44570) in rats]. AB - 1) The chronic toxicity of (-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1- ethoxycarbonyl-3 phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic++ + acid (trandolapril: RU44570), a novel angiotensin-converting enzyme blocking antihypertensive drug, was assessed in rats by oral administration for 12 months at dosage levels of 0.05, 0.25, 2.50 and 25.00 mg/kg/day, comparing with the control animals received 0.5% methylcellulose solution. Reversibility of the drug-induced changes was also examined by 3 months' withdrawal following the administration period. 2) There was no death or general symptom that was thought to be attributable to the administration of RU44570. 3) The body weight gain was significantly suppressed from 1st week to the end of administration period in male animals of the dosage groups of 2.50 mg/kg or more and from week 1 to 15 of administration in female animals of the 25.00 mg/kg dosage group. During the withdrawal period, the difference of the body weights between these groups and control was reduced and that was never statistically significant. 4) The food consumption generally tended to be lowered in male animals of the dosage groups of 2.50 mg/kg or more throughout the administration period. The values were significantly different from that of control group on almost all measurement points from week 2 to 34 of administration. The difference of the food consumption of these groups from control group tended to be smaller thereafter, although significant difference was seen sporadically. Male animals of the 0.05 and 0.25 mg/kg dosage groups also showed the tendency of decreased food consumption infrequently. There was no constant tendency of fluctuation in the food consumption among the each RU44570 treated group during the withdrawal period. 5) The water consumption increased significantly in male animals of the 25.00 mg/kg dosage group from 1st week to the end of administration period. Male animals of the 2.50 mg/kg dosage group showed similar high value of the water consumption but the degree was lesser than that of 25.00 mg/kg dosage group. Although female animals of the 25.00 mg/kg dosage group showed significantly increased water consumption from week 3 to 4 of administration, they began to show decreasing tendency from approximately week 10 of administration conversely. From week 26 of administration, the water consumption of this group significantly decreased frequently comparing with that of control group. Female animals of the 2.50 mg/kg dosage group showed similar decrease in water consumption from approximately week 26 of administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8515504 TI - [Fertility study of trandolapril (RU44570) in rats]. AB - A fertility study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day. The male rats were treated for 63 days before mating and during the mating period. The female rats were treated from 14 days before mating to day 7 of pregnancy. Each 24 male and female rats in the same dosage group were mated and female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses. No abnormal findings were observed in symptom during the administration period, however body weight gain and food consumption in both male and female animals of treated groups were lower than control group. Any adverse effects on reproductive performance were not detected. Numbers of implantations and live fetuses were decreased slightly at 30 and 300 mg/kg dosage group comparing with those of the control group. However, RU44570 did not affect fetal mortality, growth of fetuses, or the incidence of external, visceral or skeletal malformation of the fetuses. From these results, it is suggested that non-effective dose level of RU44570 is lower than 3 mg/kg for general toxicity in parent animals, 300 mg/kg for reproductive ability in parent animals, and 3 mg/kg for development in embryos and fetuses, respectively. PMID- 8515505 TI - Schwannomas of the nasal cavity. PMID- 8515506 TI - Minimal middle ear effusion: an indication for ventilation tubes in infants with protracted vomiting. AB - We have lately treated six infants hospitalized in our hospital for persistent vomiting and failure to thrive with no overt explanation for their condition. Examination of the ears of these infants revealed various degrees of serous otitis media. They all had myringostomies and insertion of ventilation tubes after which they stopped vomiting and gained in weight. We wish to revive the often overlooked association between protracted vomiting and middle ear effusion. It seems that minimal degrees of middle ear effusion may cause vomiting and patients with this condition may benefit from ventilation tubes. PMID- 8515507 TI - A monomorphic adenoma of the minor salivary glands presenting at the base of the tongue: a case report and review of the literature. AB - A case of a monomorphic adenoma of the minor salivary glands situated at the base of the tongue in a 49-year-old female is reported. The patient had a prolonged clinical course of eight years' duration. The histopathologic, immunohistologic and ultra-structural findings are described. A review of the literature concerning minor salivary gland tumors and their location in the oral cavity is presented. This is the first case, to our knowledge, of a monomorphic adenoma presenting at the base of the tongue. The difficulties in its diagnosis are discussed specifically in regard to its location. PMID- 8515508 TI - Vocal characteristics of children with cleft lip/palate and associated velopharyngeal incompetence. AB - This investigation was designed to evaluate the relationship between aerodynamic measures of velopharyngeal competence and laryngeal function in individuals with repaired cleft palate. Twenty-seven cleft lip and palate or cleft palate individuals, between the ages of 4 and 16 years, were evaluated in an ENT clinic for assessment of vocal function. A commercially available aerodynamic (pressure/flow) system for evaluating velopharyngeal function was used to classify estimated opening of the velopharyngeal port during speech production. Aerodynamic measures of laryngeal function (transglottal pressure and airflow, and laryngeal airway resistance) were also collected. A computerized system for acoustic analyses of voice production was employed to determine vocal characteristics of pitch perturbation (jitter), amplitude perturbation (shimmer) and signal-to-noise ratio (SNR). The results suggested that the cleft speakers showed numerically larger measures of perturbation in the vocal signal, and greater laryngeal airway resistance than their normal controls. Subgroups of cleft palate speakers, based on their vocal dynamics, were proposed. Implications for medical and behavioral management for these subgroups are discussed. PMID- 8515509 TI - A rare cause of reversible sensorineural hearing loss. AB - A unilateral sensorineural hearing loss that acutely develops should raise suspicion. A thorough work-up is indicated as a few reversible causes exist. Drug therapy represents probably the most common cause of a reversible sensorineural hearing loss, with a few medical conditions contributing to the list of etiologic factors. We present a case of unilateral sensorineural hearing loss in an otherwise asymptomatic patient that was attributed to non-Hodgkin's lymphoma, which reversed following chemotherapy. PMID- 8515510 TI - An anatomical study of vidian neurectomy using an endoscopic technique: a potential new application. AB - Vasomotor rhinitis is a common problem in contemporary rhinology. Although this disease has been described for decades, the pathophysiology and treatment are yet to be fully understood or described. A review of the literature of vasomotor rhinitis focusing mainly on pathophysiology and treatment is presented. Following detailed cadaver dissections a new treatment approach that takes advantage of endoscopic techniques has been proposed. Comparison with existing techniques and discussion of the pathophysiology of vasomotor rhinitis is presented. Treatment suggestions conclude the analysis, with the authors commending the endoscopic technique when symptoms merit division of the vidian nerve. PMID- 8515511 TI - Development of a surgical otology database. PMID- 8515512 TI - Radiology case of the month. The case of the migrating fish bone? PMID- 8515514 TI - Ozena. PMID- 8515513 TI - Bronchoscopic foreign bodies: overcoming granulation tissue. PMID- 8515515 TI - An unusual laryngeal hamartoma: lipofibroleiomyoma. PMID- 8515516 TI - Artificial denture in esophagus--but whose? PMID- 8515517 TI - Oh where oh where does the ear wax go? And how does it get there? PMID- 8515518 TI - An anatomic and CT scan study of the lateral wall of the sphenoid sinus as related to the transnasal transethmoid endoscopic approach. AB - Interest in endoscopic sinus surgery has expanded to include the sphenoid sinus. While the transnasal transethmoid approach is an established route to the sphenoid sinus, instrumentation is brought close to the lateral wall. This study organizes the lateral wall of the sphenoid sinus into three distinct areas. Fifteen fixed cadaver specimens, 15 fresh specimens and 25 axial as well as coronal CT scans are used to examine each area of the lateral wall. The orbital apex, spongy vascular tissue of the cavernous sinus and the internal carotid artery are found in tandem sequence adjacent to the lateral wall of the sphenoid sinus. A highly pneumatized sphenoid sinus may attenuate the bone over the lateral wall placing the optic nerve and carotid artery at greater risk. Anatomic variations, as examined in this study, and limitations imposed by endoscopic vision via the transnasal transethmoid approach dictates a need to understand the anatomy as well as familiarity with endoscopic surgery. Axial CT scans of the sphenoid sinus can image anatomic variations which may compromise safety of the lateral sphenoid sinus wall. PMID- 8515519 TI - Computer-assisted surgery of the paranasal sinuses. AB - Endonasal surgery has become a standard procedure for the treatment of diseases of the paranasal sinuses. The objective of the computer-assisted surgical system presented here is to dramatically reduce the rate of complications by improving intra-operative orientation. PMID- 8515520 TI - CT scanning for functional endoscopic sinus surgery: analysis of 200 cases with reporting scheme. AB - An analysis of the computed tomograms of the paranasal sinuses from 200 patients with sinonasal complaints is presented. The results of our study are similar to those of other reported series despite a different patient selection. We have developed a simple systematic reporting scheme which includes all of the relevant abnormalities, and which allows a much more detailed picture of the disease pattern to be generated for both clinical use and for analytical studies. PMID- 8515521 TI - The pH of secretions in sinusitis and otitis media. AB - Impaired mucociliary function is a common finding in patients with recurrent respiratory infections, sinusitis and otitis media. One main component of mucociliary transport, ciliary beating activity, is sensitive to environmental hydrogen ion concentration (pH). The pH of secretion in 103 specimens from acute or chronic sinusitis and in 98 specimens from acute or secretory otitis media were measured. There were no differences between acute and chronic sinusitis (mean of pH 7.5 +/- 0.5 and 7.4 +/- 0.6) or between mucous and purulent secretions. In acute otitis media, secretion was significantly more acidic than in secretory otitis media (mean of pH 7.7 +/- 0.5 versus 8.2 +/- 0.4). The pH was less than 7.0 in 16 (15.5%) patients with chronic sinusitis and in two (8%) patients with acute otitis. The study shows that pH of sinusal or tympanal secretion is, in the majority of patients, within limits that do not cause ciliostasis. PMID- 8515522 TI - Plasma endothelin-1 concentration in the inferior turbinate. AB - Endothelin (ET)-1 has the most potent vasocontrictive action of any substance known to date. Three milliliters of blood was removed from both the inferior turbinate and from the antecubital vein of six patients who underwent nasal surgery under general anesthesia. After centrifugation of the blood samples, the plasma was sent for radioimmunoassay of the plasma levels of ET-1. The plasma ET 1 level in the nasal blood vasculature was 6.4 +/- 1.0 pg/mL (mean +/- SEM), which was almost equivalent to that found in the antecubital vein (5.3 - 2.7 pg/mL) (N = 6). These values were greater than the normal range (1.5 +/- 0.5 pg/mL) probably because of the effect of general anesthesia. These results indicate that ET-1 is present in similar levels in the blood vessels of the inferior turbinate and the antecubital vein. A hypothesis that adrenaline induces ET production was not confirmed because topically applied adrenaline did not raise the plasma ET-1 level either in the nasal vasculature or in the peripheral vein. PMID- 8515523 TI - Sino-nasal adenocarcinoma: epidemiological and clinico-pathological study of 34 cases. AB - Thirty-four cases of sino-nasal adenocarcinoma treated between 1976 and 1992 are presented. The purpose of this work is the epidemiological analysis of this disease and to put forward a classification of the lesions according to their degree of differentiation, based on the histopathological examination of 29 tumors. The risk increase of having a sino-nasal neoplasia was significant in the population exposed to wood dust in their working environment--896 times greater (540 in the male population) for adenocarcinoma and 20 times greater for squamous cell adenocarcinoma. The proposed histopathological classification divides these lesions according to their degree of differentiation. In this series 23 well differentiated cases were found, three moderately differentiated and three colloid-type. The five-year determinate survival of this series was 30%. The tumor stage (especially intracranial involvement) was the only significant clinico-pathological parameter that impaired the survival. PMID- 8515524 TI - Obstructing adenoids in adolescents: changing trends? AB - The number of adolescents undergoing surgery for obstructing adenoids has increased significantly in our practice in recent years. Over an 11-year period during which 539 adenoidectomies were performed, the mean age of patients increased progressively from 4.6 years in 1980 to 7.88 years in 1990. The median age gradually increased over the same period from 4 to 7 years, and the standard deviation from 4.95 to 19.38. Enlarged adenoids should be considered in the differential diagnosis of adolescents suffering from nasal obstruction, snoring or obstructive sleep apnea. PMID- 8515525 TI - Wegener's granulomatosis. The great masquerade: a clinical presentation and literature review. AB - Wegener's granulomatosis is classically a systemic disease which has masqueraded as many other disorders. The patient presenting with head and neck manifestations is often initially referred to the otolaryngologist. Although the natural history of this disease is fairly well understood, its etiology and pathogenesis are not clear. The response of Wegener's granulomatosis to appropriate therapy can be dramatic, whereas without treatment it is a progressive and mutilating disorder with life-threatening complications. Two cases which were recently managed at our center are presented in an attempt to illustrate the complexity of this disorder and the diagnostic and therapeutic dilemma which it presents. A literature review was carried out and a recent concept, the Multistep Evolution Hypothesis, as well as diagnostic advances in serological testing, are discussed. Cyclophosphamide and systemic steroids, the mainstay of therapeutic intervention, as well as more recent modalities including plasmapheresis, folate antagonists, oral trimethoprim sulfamethoxazole and local radiotherapy are reviewed. PMID- 8515526 TI - Sonographic follow-up of ethanolamine oleate sclerotherapy for hydrocele. AB - Sclerotherapy has gained increasing popularity during the last few years as a treatment for hydrocele. Little is known of the natural course of intrascrotal changes, however, nor of their timetable after therapy. In the present trial scrotal ultrasonography was performed before the sclerotherapy and during the follow-up examination in the case of 70 symptomatic consecutive outpatients ranging in age from 19 to 85 years (mean, 58 years) with 71 hydroceles treated by ethanolamine oleate sclerotherapy. Posttreatment sonographic findings typically included heterogeneously echogenic extratesticular masses, cystic areas with peritesticular hyperechoic lines, and a thickened scrotal wall. All the lesions showed improvement. Sonography proved to be useful for differentiating hydroceles from spermatoceles and for evaluating the need for a renewed treatment during follow-up. Ethanolamine oleate was effective as a sclerosant, as 86% of cases were cured or significantly improved. Complications were mild and uncommon, and no intratesticular or epididymal changes were observed. Ethanolamine oleate sclerotherapy can be recommended as a treatment of choice for hydrocele. PMID- 8515527 TI - Fetal grasping at 16 weeks' gestation. PMID- 8515528 TI - Duplex Doppler sonographic examinations of the testis in prepubertal boys. AB - This retrospective study of 143 pediatric patients with unilateral acute scrotal disease was done to assess the value of duplex Doppler sonographic examination prior to puberty (110 patients) in comparison to a pubertal group (33 patients) in a pediatric hospital, where the examinations are done by staff radiologists and radiology residents of varying degrees of expertise and experience with Doppler technique. All patients seen during an 18 month period were included. The unaffected side was examined in most patients and served as control. The normal Doppler shift in the center of the prepubertal testis was found to be 0.2 to 0.5 kHz, when using a 5 MHz duplex Doppler probe. With puberty, the Doppler shift increased to 0.5 to 1 kHz. Of 18 patients (10 prepubertal) with testicular torsion, five (three prepubertal) had false-positive Doppler shift. In four of these five cases, faulty placement of the Doppler sample volume cursor was probably the cause. Using a multi-way frequency analysis, puberty was found to have no significant influence on results of Doppler signal (chi square = 0.1346; P = 0.7137). Duplex Doppler sonographic examination is as useful to rule out testicular torsion in prepubertal boys as it is after puberty. Meticulous technique is essential. The opposite side should be examined first and serves as control for the affected one. Results showing no flow in the center of the diseased testis with positive flow in the unaffected one should lead to further clinical action (scintigraphy or surgery). PMID- 8515529 TI - Caudal regression versus sirenomelia: sonographic clues. AB - Seven cases with the pathologic/autopsy diagnosis of caudal regression or sirenomelia in which antenatal sonography had been performed were reviewed. The three patients with caudal regression had similar findings on antenatal sonogram, including normal or increased amniotic fluid, mild dilation or normal urinary systems, nonfused extremities, and sacral agenesis. In the four patients with sirenomelia, common sonographic findings included marked oligohydramnios, suspected renal agenesis, and sacral agenesis. A history of maternal diabetes was elicited in all patients with caudal regression and in none of the patients with sirenomelia. Findings confirm recent articles in pediatric pathology suggesting that caudal regression is a separate entity, distinct from sirenomelia. PMID- 8515530 TI - Premaxillary protrusion: a sonographic clue to bilateral cleft lip and palate. AB - Sonograms from 49 fetuses with cleft lip, with or without cleft palate, were reviewed. Among 37 fetuses with adequate pathologic or clinical correlation, 10 (27%) demonstrated premaxillary protrusion, seen as a paranasal echogenic mass. Nine of ten fetuses with a paranasal echogenic mass proved to have bilateral cleft lip and cleft palate. Conversely, only two of 27 fetuses who did not show a paranasal echogenic mass proved to have bilateral cleft lip and cleft palate, and neither of these fetuses showed premaxillary protrusion at birth. Sonographic evaluation of the cleft alone erroneously misclassified eight fetuses with bilateral cleft lip and cleft palate as having unilateral clefts. Premaxillary protrusion is an important clue to the presence of cleft lip and cleft palate and may be more conspicuous than the cleft itself. Furthermore, the presence of a paranasal echogenic mass favors the presence of bilateral cleft lip and cleft palate, even when sonographic evaluation of the cleft itself suggests a unilateral cleft. This information should be useful in the detection and management of fetuses with suspected facial clefts. PMID- 8515532 TI - Color Doppler sonography of vascular malformations of the liver. AB - Nine cases of intrahepatic vascular malformations diagnosed using color Doppler sonography are described. These consisted of six cases of intrahepatic portal hepatic venous shunts and three cases of arteriovenous fistulas. Among these is a case of multiple intrahepatic portal-systemic shunts. The sonographic findings and theories explaining the formation of vascular malformations in the liver are discussed. PMID- 8515531 TI - Duplex Doppler sonography of celiac trunk and superior mesenteric artery: comparison with intra-arterial angiography. AB - DDS was compared to intra-arterial angiography for the diagnosis of significant (> 50%) stenoses of the celiac trunk and the SMA in 38 consecutive patients referred for angiographic evaluation of peripheral arterial occlusive disease. Celiac trunk occlusion was correctly identified by DDS in three of three patients. In patients with significant celiac trunk stenoses, mean peak systolic velocity was 246 (+/- 154) cm/sec and differed significantly (P < 0.05) from the peak systolic velocity (101 +/- 22 cm/sec) of 22 patients with no angiographic evidence of significant stenosis. Five false-negative DDS examinations in patients with > 50% celiac trunk stenoses were noted. Using a peak systolic velocity of > 160 cm/sec (mean value in normal vessels plus 3 standard deviations) to diagnose > 50% celiac trunk stenosis, sensitivity of DDS was 57% and specificity was 100%. However, considering celiac trunk stenoses and occlusions as a single group, the sensitivity rate of DDS in diagnosing significant stenosis and occlusion of celiac trunk was 70%. PMID- 8515533 TI - Dilation of venous vessels at the splenic hilum in normal sized spleens as an indication of pathologic splenic involvement: preliminary results. AB - Twelve hundred patients without liver or heart disease, having a normal sized spleen without focal lesions, were examined by ultrasonography to measure the inner diameter of the splenic vein in relation to possible current or recent recovery from pathologic processes. SVD was measured at the hilum of the spleen with the patients supine. Ten of the patients in whom dilation of the SVD was found, together with a group of healthy controls (25), were subsequently studied with a duplex Doppler analysis to measure the venous outflow from the spleen. The results showed 1,175 spleens (98%) with SVD at the hilum of < 8 mm and 25 spleens (2%) with SVD of > 8 mm. Twenty-three of 25 patients (92%) with enlarged SVD had recent histories of hematopoietic or infectious diseases. Ten of 23 patients with enlarged SVD were studied further with a Doppler analysis. They demonstrated a rapid splenic blood flow with maximum flow velocities ranging from 14 to 27 cm/sec and high outflow volumes (from 430 to 1,227 ml/min, averaging 786 ml/min +/- 266), both significantly increased in comparison with controls (outflow volume from 200 to 355 ml/min, averaging 274 +/- 40; P < 0.0001). We conclude that dilation of the SVD accompanied by an increased intrasplenic blood flow volume without splenic enlargement would indicate a state of increased perfusion of splenic tissue associated with an immune response, reflecting reaction of the spleen to disease. PMID- 8515534 TI - Celiac artery aneurysm: color Doppler evaluation. PMID- 8515535 TI - Color Doppler imaging aids in the prenatal diagnosis of congenital diaphragmatic hernia. PMID- 8515536 TI - Cholelithiasis in Canavan disease. PMID- 8515537 TI - Post cesarean delivery atonic bladder with overflow incontinence appearing sonographically as a large retrovesical hypoechoic mass. PMID- 8515538 TI - [Effect of enflurane on human somatosensory evoked potentials: differences between specific and nonspecific responses]. AB - The effect of enflurane on somatosensory evoked potentials (SEP) was investigated in nine gynecological patients under nitrous oxide-enflurane anesthesia. SEPs were obtained from electrodes placed on the scalp C4 and earlobes by median nerve stimulation contralateral to the recording site. SEPs taken in a control study without enflurane consisted of six components; P12, N17, P23, N31, P50, and N65. Components N17, P23, N31, and P50, thought to be specific SEP responses, showed a dose-dependent increase in latencies under enflurane while P12, the initial SEP components, did not show any significant changes throughout the experiment. The longer the latency for a given response component, the greater was the increase in latency seen under enflurane anesthesia. On the other hand, N65, assumed to be a nonspecific SEP response, was completely lost with inhalation of 0.5 MAC or more of enflurane. However, the peak-to-peak amplitude between P23 and N31 was enhanced dose-dependently with enflurane up to 1.5 MAC. These results suggest that, at clinically effective doses, enflurane may inhibit nonspecific projection pathways while enhancing the primary cortical sensory area, and this enhancement may be responsible for provoking convulsive seizures under enflurane anesthesia. PMID- 8515539 TI - [Changes in microcirculation in the facial nerve with electrical stimulation and chemical blockade of cervical sympathetic trunks]. AB - The cervical sympathetic trunks send peripheral branches to the external carotid artery system which in turn provides feeding vessels to the facial nerves. In this study, the changes in the tonus of these trunks and the associated changes in the microcirculation of the facial nerves were studied by electrical stimulation and by chemical blockade of the cervical sympathetic trunks in mongrel dogs. With electrical stimulation, marked increases in arterial blood pressure and the heart rate were observed although the common carotid arterial blood flow and tissue blood flow in facial nerves decreased markedly. This suggests that microcirculation in the facial nerve is definitely impaired by electrical stimulation of the cervical sympathetic trunks and that hypertonicity of the sympathetic nervous system is closely involved in the onset of facial palsy. When chemical blockade was applied to the same trunks, the arterial blood pressure and heart rate showed no significant changes. However, there were marked increases of the blood flow in common carotid artery and facial nerve tissue. This finding of improved microcirculation in the facial nerve after chemical blockade suggests that stellate ganglion block may be a very effective treatment for Bell's palsy. PMID- 8515540 TI - [Effect of intravenous lidocaine infusion on arterial baroreflex]. AB - The purpose of the first study was to identify the relationship between reflex sympathetic nerve activity and plasma concentration of lidocaine. Lidocaine was infused in 4 different doses: 2 mg.kg-1 bolus + 100 micrograms.kg-1 x min-1, 3 mg.kg-1 bolus + 200 micrograms.kg-1 x min-1, 6 mg.kg-1 bolus + 400 micrograms.kg 1 x min-1 and 12 mg.kg-1 bolus + 800 micrograms.kg-1 x min-1. Baroreflex depressor and pressor tests using sodium nitroprusside (5-10 micrograms.kg-1) and phenylephrine (2-4 micrograms.kg-1) were performed before and at 10 min after the start of lidocaine infusion. Plasma lidocaine concentrations determined by HPLC revealed that its steady-state levels were maintained during the baroreflex tests. Baroreflex sensitivity was preserved at clinical concentrations of lidocaine (< 5 micrograms.ml-1). However, baroreflex was significantly attenuated when plasma lidocaine concentrations were above seizure levels (> 10 micrograms.ml-1). This result indicates that hemodynamic derangement observed in the lidocaine-induced CNS toxicity is, at least in part, due to the attenuated arterial baroreflex. In the second study, the author evaluated the effect of respiratory acidosis and alkalosis on the baroreflex with or without lidocaine infusion (2 mg.kg-1 + 100 micrograms.kg-1 x min-1). Respiratory acidosis (PaCO2: 65.6 +/- 3.4) enhanced the baroreflex significantly, but lidocaine infusion abolished this acidosis-induced enhancement. The author concludes that hypercarbia should be avoided in patients receiving intravenous lidocaine infusion. PMID- 8515541 TI - [Epidural opioids for post-operative pain control in pediatric patients with cerebral palsy]. AB - The safety and efficacy of epidural opioids as postoperative analgesics for children with cerebral palsy were studied in 85 pediatric patients with cerebral palsy. The patients were 5 to 15 years of age and were undergoing elective orthopedic operations on the lower extremities. These patients were divided into four groups. All the patients received inhalational anesthesia combined with caudal anesthesia, while the patients in groups 2, 3, and 4 were given epidural morphine (40 micrograms.kg-1), buprenorphine (3 micrograms.kg-1), or butorphanol (30 micrograms.kg-1) at the end of operation, respectively. Number of patients who received analgesics more than 2 times within 24 hours after operation was larger in group 1 than in groups 2-4. Although groups 2-4 compared with group 1 were still sedated at 24 hours after the operation, there was no difference in degree of sedation among the groups 2-4. The epidural opioids did not increase the frequency of side effects such as nausea, vomiting etc. The authors conclude that epidural opioids achieve safe and useful postoperative pain control in children with cerebral palsy. PMID- 8515542 TI - [Intrapleural regional analgesia in pain management after chest trauma]. AB - Twelve chest trauma patients with severe pain were studied. All of them had multiple rib fractures, hemopneumothorax or pulmonary contusion, and needed the continuous chest drainage. 16 G epidural block catheter was introduced 20 cm into the apex of the pleural space. Furthermore, another catheter was placed into the base of the pleural space. After injecting 1% lidocaine 10 ml, the analgesic effect, the analgesic range according to injected point (apex or base), and the changes of vital signs, PaO2/FIO2 and PaCO2 were evaluated. The average pain scale before interpleural regional analgesia (IPA) was 2.9 and 1.0 after 15 min. The time to return to pre-IPA condition took about 150 min. The mean blood pressure did not show significant changes, although pulse and respiratory rate decreased. PaCO2 did not show significant changes, although PaO2/FIO2 increased significantly. The present study indicates that IPA in chest trauma reduces pain and improves PaO2/FIO2 significantly without circulatory changes. It was reported that it was difficult to obtain effective pain relief after thoracotomy. However, when the catheter is placed at the apex, it seems to be effective to relief pain on the chest site. In conclusion, IPA seems to be simple, effective and useful to remove pain from chest trauma when epidural block is difficult to induce. PMID- 8515543 TI - [Effect of hemodilutional autotransfusion on coagulative-fibrinolytic dynamics and metabolic response]. AB - We studied the effect of hemodilutional autotransfusion on coagulative fibrinolytic dynamics and metabolic response. Hemodilutional solutions used were Dextran-40 (group A) and Salin-HES (group B). The activated partial thromboplastin time (APTT) immediately after hemodilution was prolonged in both groups. Prothrombin time (PT) and hepaplastin decreased significantly, and a remarkable variation was observed particularly in group A. The results suggest that effect on fibrinolytic dynamics is not exerted in either group because antithrombin-III (AT-III) and fibrinogen decreased significantly, while fibrinogen degradation products (FDP) are within normal ranges, and plasminogen as well as alpha 2-plasmin inhibitor (alpha 2-PI) decreased significantly. On the other hand, all other parameters such as lactic acid level, pyruvic acid level in blood, lactic acid pyruvic acid ratio, and blood glucose level were elevated during surgery, but no difference was observed regarding these parameters between the two groups. PMID- 8515544 TI - [The circulatory and respiratory effects of methylprednisolone associated with catecholamine administration of a few hours]. AB - We studied the circulatory and respiratory effects of methylprednisolone (MPS) associated with catecholamine administration of a few hours after cardiopulmonary bypass (CPB). Forty patients undergoing coronary artery bypass grafting were randomly divided into two groups. Twenty patients in group 1 [MPS (-) group] did not receive MPS and 20 patients in group 2 [MPS (+) group] received MPS 15 mg.kg 1 i.v. 60 minutes after CPB. The circulatory and respiratory parameters were measured 60 minutes after CPB, 30 minutes after MPS i.v. and 60 minutes after MPS i.v. The values in MPS (-) group were compared with those in MPS (+) group. CI and SVI decreased, and SVRI and PQR increased in MPS (-) group, but these values were unchanged in MPS (+) group. RAP, mPAP, PCWP and PVRI were unchanged in MPS ( ) group. PCWP increased and the other values were unchanged in MPS (+) group. The blood gases and pulmonary alveolar function were not different between the two groups. The oxygen delivery decreased in MPS (-) group, but it was unchanged in MPS (+) group. The oxygen consumption was unchanged in the two groups. Blood cortisol increased and epinephrine and norepinephrine decreased in MPS (+) group. Methylprednisolone had an effect to improve the decreased CI and the increased SVRI, and no respiratory problems were observed in patients for coronary artery bypass grafting with catecholamine administration for a few hours after cardiopulmonary bypass. PMID- 8515545 TI - [Postoperative anti-emetic effects of low dose droperidol]. AB - We studied the postoperative anti-emetic effects of low dose droperidol which was compared with that of metoclopramide in 60 gynecological patients. The effects at the third and 24th hours after surgery were evaluated by means of the nausea and vomiting score; 0 = none, 1 = discomfort, 2 = nausea, 3 = vomiting. The sores of postoperative nausea and vomiting within 3 hours after operation showed no significant difference between droperidol and metoclopramide groups (D: 0.2 +/- 0.4, M: 0.3 +/- 0.6). However, there was a significant difference between the two groups after 24 hours (D: 0.2 +/- 0.5, M: 0.8 +/- 1.0). We conclude that droperidol has a potent antiemetic effect that lasts after 24 hours. PMID- 8515546 TI - [Reversal by the calcium ion of the pain threshold elevated by calcium channel blockers]. AB - We investigated calcium ion effects on pain thresholds by iontophoresis in healthy adult volunteers. The pain thresholds were measured by the pain thermometer to evaluate the effect of iontophoresis. At first, one of calcium channel blockers (nicardipine, verapamil or diltiazem) was administered by iontophoresis with 1.0 mA for 10 minutes. Then, next to calcium channel blockers, calcium chloride or saline was locally administered after the elevation of pain threshold had been recognized and the pain threshold had been measured again. Calcium ion decreased the elevation of pain threshold significantly, but saline had no effect. These results suggest that not only sodium channel but also calcium channel influences pain mechanism during iontophoresis. PMID- 8515547 TI - [The usefulness of a pulse oximeter on the postanesthesia round]. AB - In our hospital, a patient must be transported to one of several types of wards according to the degree of severity of illness (PPC-system). Severely ill patients are surveyed in ICU and HCU with various kinds of monitors. On the contrary, for the patients outside the ICU and HCU wards, the number of monitors is not enough even during postoperative periods. Therefore, we studied the occurrence of hypoxic state of patients with a portable pulse oximeter on postanesthesia round. We surveyed 843 patients during 4 months, and found 79 hypoxemic patients. The number of hypoxemic patients was greater not only after longer operations and anesthesia, but also in obese patients (P < 0.05) as reported previously. Interestingly, we also found more hypoxemic patients in common wards than in ICU and HCU wards. In conclusion, a portable pulse oximeter is a useful equipment in ordinary wards during postanesthesia round. PMID- 8515548 TI - [Optimal glucose dose in the preoperative fluid infusion]. AB - We have measured blood concentrations of glucose, 3-hydroxybutyrate (3-OHBA), non esterified fatty acid (NEFA) and lactate before and after glucose administration in 105 patients to determine the optimal glucose dose during the period of preoperative fasting state. The patients, scheduled for laparotomy in the afternoon, received fluid infusion containing an arbitrary glucose dose for 4 hours prior to surgery. The glucose dose showed a negative correlation with the ratio of 3-OHBA or NEFA prior to and after glucose administration (r = 0.40, r = 0.41 respectively, P < 0.05). There was no correlation between lactate ratio and glucose dose (r = 0.06). Glucose administration more than 0.4 g.kg-1 significantly suppressed 3-OHBA production (P < 0.05). Hyperglycemia (> 200 mg.dl 1) developed more often in the groups given 0.5 g.kg-1 or more glucose (P < 0.05), while significant hypoglycemia (< 60 mg.dl-1) occurred in the groups given less than 0.2 g.kg-1 of glucose (P < 0.05). This study demonstrates that preoperative infusion of glucose 0.4-0.5 g.kg-1 is useful to maintain the energy metabolism during the fasting state in patients scheduled for operation in the afternoon. PMID- 8515549 TI - [Left ventricular function during hypoxia. 1: Effect of blood glucose level]. AB - We investigated the effects of blood glucose levels and myocardial glucose uptake on cardiac function during hypoxia in mongrel dogs (N = 50). During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low concentration of oxygen for 2 hours, left ventricular (LV) function including LV pressure, maximum rate of rise of LV pressure, and cardiac index decreased significantly following initial enhancement. There were significant correlations between these hemodynamic parameters and blood glucose levels. The blood glucose levels correlated significantly with myocardial glucose uptake and blood lactic acid levels (r = 0.660: P = 0.000, r = 0.380: P = 0.000, respectively). Eight of nine dogs which died within 90 minutes during hypoxia showed low blood glucose levels and high lactic acid levels. During hypoxia, myocardial glucose uptake increased to more than five times of control value. On the other hand myocardial lactic acid uptake decreased and turned to production. At the same degree of blood lactic acid levels, LV function was maintained better with high blood glucose levels than with low levels. With low blood glucose levels, myocardial lactic acid uptake and production tended to cease. The pronounced change in LV function during hypoxia could be partially explained by decreased production of ATP due to decrease in myocardial glucose uptake and high lactic acid levels. It seems that high blood glucose levels are preferable to maintain cardiac performance under such a condition. PMID- 8515550 TI - [The effects of prostaglandin E1 on the release of beta-glucuronidase in leukocyte and granulocyte elastase in patients for major abdominal surgery]. AB - We have studied the effects of prostaglandin E1 (PGE1) on the release of lysosomal enzymes such as beta-glucuronidase in leukocyte (beta-GL) and granulocyte elastase (GEL) in 52 patients for major abdominal surgery. All patients were divided into two groups; the PG group (24 patients) and the control group (28 patients). The patients of the PG group received PGE1 continuously at the rate of 0.03 to 0.1 micrograms.kg-1.min-1 during surgery. Plasma levels of GEL and beta-GL, which are known to be the indicators of tissue destruction, were measured during and after surgery. The GEL/granulocyte ratio in the PG group was significantly smaller than that of the control group during surgery. The rate of change of beta-GL was significantly depressed in the PG group compared to that of the control group. These findings suggest that the administration of PGE1 during major abdominal surgery inhibits the release of lysosomal enzymes, and this prevents tissue injury during and after surgery. PMID- 8515551 TI - [The effects of two and five percent aqueous phenol on the cat tibial nerve in situ--the local anesthetic-like effect of aqueous phenol]. AB - Phenol is well known as a neurolytic agent because of its denaturing property on protein, but many pain clinicians recognized that it has transient nerve blocking effect like local anesthetics in some cases. This investigation was planned to understand the local anesthetic like effect of phenol with the cat tibial nerve model, while its blood flow was kept intact. The tibial nerve was stimulated electrically every one second, and the compound action potentials of its A-fibers were recorded with an oscilloscope for two hours. Physiological saline solution (PSS), 2% lidocaine and 2% and 5% aqueous phenol were injected into the nerve fibers through a glass capillary tube. In the case of PSS, no remarkable change was recognized during the experiment. The action potentials were depressed to 26.5% of control value 10 minutes after injection in 2% lidocaine group and returned to control levels at the end of observation. In almost all cases of 5% aqueous phenol group the action potentials vanished soon after injection. Some interesting phenomena, the biphasic depression of the action potentials, were observed in 2% aqueous phenol group. The first depression was recognized soon after injection of 2% aqueous phenol, which was faster than that with the 2% lidocaine. After the transient recovery of the action potential, the second depression appeared after thirty minutes. This delayed depression was considered to be due to circulatory damage of the nerve fibers by phenol. PMID- 8515552 TI - [Use of Bayesian estimation as a diagnostic tool in clinical practice]. AB - If one of the monitors indicates that perioperative myocardial ischemia is occurring, is it telling the truth or what is the probability of its telling the truth? This kind of question is imperative in the conduct of safe anesthesia practice. For this reason, we need to know, so called, the predictive value, which is essentially an application of Bayesian estimation. In this paper, fundamental knowledge and pitfalls in the issue of Bayesian estimation in relation to a predictive value are discussed and summarized. Prior probability, identical to the concept of prevalence is joined together with available information to form a posterior probability or a predictive value to make any clinically relevant decisions. The terms, sensitivity and specificity are defined and their relation to the predictive value is discussed as well. The architecture of Bayesian estimation is explained by taking examples from the literature. PMID- 8515553 TI - [Anesthetic experience of emergency cesarean section for a patient with myotonic dystrophy]. AB - We report an anesthetic experience of a 28-year-old female patient complicated with myotonic dystrophy who underwent emergency Cesarean section due to threatened abortion. Anesthesia was induced with intravenous thiopental followed by topical spray of 4% lidocaine 5 ml to intubate trachea and maintained with neuroleptanesthesia with droperidol, fentanyl and nitrous oxide in oxygen. No muscle relaxant was used. The course of anesthesia and emergence from anesthesia were uneventful. However, the female infant, with Apgar score of 1 point at five minutes after delivery, died due to multiple organ failure three weeks after the delivery. Anesthetic management of a patient with myotonic dystrophy was also discussed with a literature review. PMID- 8515554 TI - [Sevoflurane anesthesia in a patient following renal transplantation]. AB - A 29-year-old male after renal transplantation with aseptic necrosis of the head of the left femur was anesthetized with sevoflurane-nitrous oxide-oxygen for replacement surgery. Anesthesia was induced with N2O 4 l.min-1, O2 2 l.min-1, plus sevoflurane and maintained with N2O4 l.min-1, O2 2 l.min-1 and sevoflurane. Sevoflurane concentrations ranged from 1% to 4%. The serum inorganic fluoride showed the peak level of 38.4 microM.l-1 about 60 minutes after discontinuation of sevoflurane a decrease in serum inorganic fluoride was delayed. Urinary N acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP) and beta 2-microglobulin (beta 2-m) increased over five postoperative days. NAG and gamma-GTP returned to the preanesthetic level on the 6th postoperative day, but beta 2-m higher than the preanesthetic level lasted for 14 postoperative days. In conclusion, sevoflurane brought about little effect on the transplanted kidney in this patient. PMID- 8515555 TI - [Anesthesia for a patient with red cell aldolase deficiency]. AB - Aldolase deficiency of red blood cell is a rare cause of hereditary hemolytic anemia and now there exists only three patients in the world. We had a 24-year old man operated on for gallbladder stone secondary to this uncommon disease. He underwent a cholecystectomy under general anesthesia combined with thoracic epidural block, using isoflurane, fentanyl, vecuronium, midazolam and lidocaine. During the surgery serum concentrations of bilirubin, free hemoglobin and LDH showed no change, suggesting a lower incidence of drug-induced hemolysis in the case of aldolase deficiency than in other enzyme deficiency. This fact also provides a useful guide to the choice of anesthetics and related agents. In the postoperative period, however, we found a hemolytic response to fever with a drop in hemoglobin level to 2.5 g.dl-1. Aldolase activity of his red cell is heat labile and an increase in body temperature may aggravate a disturbance in the glycolytic pathway leading to hemolytic crisis. It is thus important to prevent the body temperature from rising when a patient is suffering from hemolytic anemia due to red cell aldolase deficiency. PMID- 8515556 TI - [Resistance to anticoagulant activity of heparin in a patient for cardiac surgery]. AB - Resistance to anticoagulant activity of heparin was observed in a patient for cardiac surgery. The activated coagulation time (ACT) was maintained over 300 seconds with additional doses of heparin which mounted to the total of 29 ml in 3 hours during cardiopulmonary bypass. Although antithrombin-III activity was not measured in this case, the heparin resistance might have been caused by the decrease in the activity of antithrombin-III which might have resulted from the preoperative malnutrition, infection of urinary tract and/or institution of intraaortic balloon pumping (IABP). PMID- 8515557 TI - [A case report of cardiac failure caused by the new anti-neoplastic agent 'carboplatin']. AB - Carboplatin is one of most commonly used chemotherapeutic agents in clinical oncology practice. We presented a case of subacute cardiotoxicity supposedly due to carboplatin. A patient with ovarian cancer had been treated with carboplatin based chemotherapeutic agent for about a month before surgery. Although she had not shown symptoms of cardiac failure, severe pulmonary edema developed immediately after general anesthesia. It disappeared within a week. For three days following the administration of carboplatin alone for two weeks after surgery, arrhythmias (SVT, SVPB and VPB) and hypotension appeared. Symptoms of congestive heart failure, resembling dilated cardiomyopathy, lasted for one month. It required about two months to restore the normal cardiac functions. Carboplatin seems to have infrequent but possible cardiotoxicity as many other chemotherapeutic agents. PMID- 8515558 TI - [Brachial plexus block with a nerve stimulator and "around the needle" catheter technique]. AB - Brachial plexus block using a nerve stimulator is an accurate procedure. But prolonged analgesic effect can not be obtained. Therefore we used "around the needle" catheter technique to have a long analgesic effect. A 20-gauge, 5-inch intravenous catheter (Angiocath) was threaded over a 23-gauge, 10-cm needle (Pole). We used axillary approach. The cathode of the nerve stimulator (NS-2CA, Professional Instrument company) is connected to the needle, and its anode is connected to the electrode on the surface of the skin. When the needle is introduced and advanced, 1 mA of electric current is applied for nerve stimulation. When the muscle twitch is obtained, a plastic cannula is then threaded off the needle into the axillary sheath. An infusion tube and three way stopcock is connected to the cannula. From 1988 to 1991 we had 31 cases. The success rate is about 90%. If we stimulate other nerves in the same sheath, it is not necessary to seek aimed one. But the musculocutaneous nerve is the only exception, because it may be stimulated outside the neurovascular sheath. PMID- 8515559 TI - [Fatigue and stress of anesthesiologists at work]. AB - We studied the fatigue and stress of anesthesiologists at work using a flicker photometer, visual reaction time test and questionnaires to them. The two kinds of visual apparatus enabled us to measure two types of fatigue. On the other hand, the questionnaires relating to fatigue and stress indicated the stress tendencies and stressors by age, anesthetic experience, and sex. The results suggest that these methods are useful for measuring the fatigue and stress of anesthesiologists. PMID- 8515560 TI - [Antimicrobial susceptibility patterns of the Proteeae in Japan, 1989]. AB - We discussed the antimicrobial susceptibilities of Proteeae isolated in Japan, 1989. Eight hundred six clinical isolates were collected from 47 hospitals. These were comprised of 431 strains of Proteus mirabilis, 155 Proteus vulgaris, 154 Morganella morganii, 44 Providencia rettgeri and 22 Providencia stuartii. Antibiotics tested in this study were 2 penicillins, 5 cephems, 1 carbapenem and 2 aminoglycosides. The MIC's were determined using the standard method of the Japan Society of Chemotherapy. Susceptibilities of the above strains to these antibiotics are described below; 1. Latamoxef, ceftizoxime and imipenem had excellent activities with no evident differences among the species of Proteeae. 2. Ampicillin and cefazolin were less active against Indol-positive Proteeae. 3. Piperacillin and cefmetazole were also strongly active drugs against P. mirabilis, P. vulgaris and P. stuartii, and cefotiam against P. mirabilis and P. stuartii. 4. Gentamicin and netilmicin showed excellent activities against M. morganii. PMID- 8515561 TI - [Antimicrobial activities of aspoxicillin of fresh clinical isolates]. AB - The Antimicrobial activity of aspoxicillin (ASPC) in terms of minimum inhibitory concentration (MICs) was compared with those of other penicillin antibiotics (PCs) against clinical isolates sent to us from medical institutions throughout Japan in 1988, 1990 and 1992 and strains isolated and identified from samples collected from patients with various infections. 1. The MIC80's of ASPC against Staphylococcus aureus, Enterococcus spp., Escherichia coli, Bacteroides fragilis group were almost the same as those against these isolates in 1985 to 1986. 2. A trend for increasing susceptibility to PCs including ASPC was observed in the isolates of S. aureus and Haemophilus influenzae. This trend in S. aureus was attributed to the appearance of non beta-lactamase producing strains associated with the development of highly resistant strains among the methicillin-resistant S. aureus (MRSA) as well as to a tendency toward yearly decreasing frequency of MRSA. The trend for the increased susceptibility in H. influenzae was related to the decrease in the number of beta-lactamase production strains. 3. The frequency of the strains highly resistant to PCs including ASPC increased. 4. No PCs resistant strains were observed among the so-called beta-streptococci, while among alpha-streptococci and Streptococcus pneumoniae there was a trend for decreasing frequency of strains with lower susceptibility to PCs or those with resistant to PCs. These strains may be variants which were also resistant to cephems and had penicillin-binding proteins (PBPs). Meanwhile, a high frequency of highly PCs-resistant strains were noted among Enterococcus faecium. In view of the fact that the PCs-resistance of E. faecium is known to be related to PBPs, the pattern of the susceptibility of the recent clinical isolates to beta-lactams is considered to be multimodal. PMID- 8515562 TI - [Therapeutic efficacy of cefodizime in combination with minocycline against systemic infection caused by methicillin-resistant Staphylococcus aureus in immunocompromised tumour bearing mice]. AB - The in vivo synergistic effect of cefodizime (CDZM) in combination with minocycline (MINO) against methicillin-resistant Staphylococcus aureus (MRSA) was investigated. A study of fractional effective dose (FED) index showed that either synergistic or additive effect was observed between CDZM and MINO. The postantibiotic effect (PAE) of MINO was not altered by the addition of CDZM. However, a strong synergistic bactericidal effect of CDZM and MINO against MRSA CT-18 was observed for more than 14 hours in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN). These results suggest that the strong therapeutic efficacy of CDZM in combination with MINO was caused by synergistic bactericidal effect of the 2 drugs in the presence of PMN. PMID- 8515563 TI - [Lactoferrin in cervical mucus of patients with chorioamnionitis]. AB - The antimicrobial activity of cervical mucus is regarded as a local defense mechanism against ascending infections by the vaginal bacterial flora. In this study, the content of lactoferrin in cervical mucus of patients with chorioamnionitis (CAM) and its correlation with other indicators of infection were determined. The results obtained are summarized as follows: 1. The lactoferrin content in cervical mucous was higher in pregnant than in non pregnant women. It was significantly lower in CAM(+) patients than in CAM(-) patients (P < 0.001) in preterm labor and was lower in preterm labor than in full term control (P < 0.002). Elastase contents in cervical mucus of CAM(+) patients were significantly higher than full-term control levels (P < 0.001), and showed a negative correlation with lactoferrin contents. 2. With regard to other indicators of infection, CRP, ESR, and WBC were higher in CAM(+) patients and fibronectin was detected (> 50 ng/ml) in the cervical mucus of all CAM(+) patients. PMID- 8515564 TI - [Protein binding of oral cephems in patients with chronic renal failure]. AB - An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects. PMID- 8515565 TI - [Chemoprophylaxis of ophthalmia neonatorum through vertical infection. Evaluation of Crede's method using norfloxacin and gentamicin]. AB - Crede's method was evaluated using norfloxacin (NFLX) and gentamicin (GM) to show the clinical significance of chemoprophylaxis against ophthalmia neonatorum occurring through vertical infections. The obtained results are summarized as follows. 1. NFLX and GM were separately instilled using Crede's original method in 171 cases selected from all cases of delivery encountered in this hospital during a period of 5 months in 1991. The two groups had similar backgrounds. 2. NFLX and GM were effective in 70 of 71 cases and in 96 of 100 cases, respectively. No side effects were found in either groups. 3. From 4 of 5 ineffective cases were isolated staphylococci, which were sensitive to NFLX and GM. PMID- 8515566 TI - Effective renal plasma flow response and atrial natriuretic peptide in patients with uncomplicated acute myocardial infarction. AB - Effective renal plasma flow was determined by using I-131 labeled iodo-ortho hippurate in 17 Chinese patients admitted to the coronary care unit with uncomplicated acute myocardial infarction. The first determination, immediately after admission, was significantly higher than the second determination done a week later, 444.5 +/- 153.9 vs. 371.1 +/- 124.9 ml/min (p < 0.02). The initial rise of effective renal plasma flow (ERPF) after acute myocardial infarction seemed to be correlated to the initial elevation of atrial natriuretic peptide (ANP), which was determined sequentially 6 times in each patient (91.3 +/- 39.4, 25.6 +/- 9.7, 37.4 +/- 12.3, 51.8 +/- 18.2, 65.6 +/- 20.8, 57.4 +/- 19.2 pg/ml, respectively). It was concluded that, in the presence of uncomplicated acute myocardial infarction, patients may show renal vasodilatation, and that the elevation of ANP may play some role in this. PMID- 8515567 TI - Valve replacement due to tricuspid valve anomalies in corrected transposition. AB - Left atrioventricular (A-V) valve anomalies are very frequent in corrected transposition, but left A-V valve replacement has seldom been reported. These anomalies are an important cause of morbidity and mortality in these patients, and due to anatomical presentation valve replacement may be difficult. We present 4 cases of left A-V valve replacement with emphasis given to Ebstein's anomaly of the left A-V valve. PMID- 8515568 TI - Coronary angiographic features in 2,234 patients with clinical suspicion of coronary heart disease without modifiable risk factors. AB - Among 12,720 patients subjected to coronary angiography because of clinical suspicion of coronary heart disease, 2,234 (78% men and 22% women) were free from major modifiable coronary risk factors. They did not report alcohol consumption, use of antiplatelet or lipid lowering agents, oral contraceptives or sex hormones; there was no history of bilateral oophorectomy, smoking, diabetes mellitus, hypertension, or obesity; the ratio of total to high-density lipoprotein cholesterol was < or = 4.5. We examined lesions causing > or = 50% stenosis to total obliteration of the 3 great coronary arteries or of their major branches, and classified these patients as having single-, double-, or triple vessel disease, or normal angiograms (no luminal irregularities). We related the extent of the coronary angiographic involvement to age and sex. From the fourth to the eighth decade of life: a) prevalence of normal angiography was significantly higher in women; b) percentage of cases with single-vessel disease was similar in both sexes and gradually reduced with aging; c) prevalence of double-vessel disease in women did not vary significantly, although a slight decline was seen at older ages; in men figures at the fifth and sixth decades were significantly greater than in women; d) percentages by decade of triple vessel disease in males were 24, 34, 41, 49 and 57%, respectively; corresponding values in women were 11, 13, 15, 27 and 44% (p < 0.01 at each decade of age); with advances of age the sex gap in triple-vessel disease narrowed, but did not disappear. Thus, atherosclerosis tended with age to involve more vessels rather than more subjects in both genders, indicating that in the absence of modifiable coronary risk factors coronary vessels remained clearly susceptible to the influence of age, both in men and women. In these patients the feminine gender exerted a substantial protection that persisted for the entire span of life. PMID- 8515569 TI - Late percutaneous extraction of an intracardiac catheter fragment. AB - A patient was found to have a mobile catheter fragment in the right atrium incidentally during echocardiography. On further investigation, it was learned that the catheter had been inserted 9 years earlier during surgery and had probably been broken during removal. The patient did not experience any symptoms during this period. The catheter was removed percutaneously without any complications using a system similar to the loopsnare catheter. PMID- 8515570 TI - The signal-averaged electrocardiogram of P wave in patients with documented atrial fibrillation or flutter and in patients with left or right atrial overload without atrial fibrillation. AB - To evaluate the significance of the signal-averaged P wave in various pathological conditions of the atrium, signal-averaged electrocardiograms and echocardiograms were studied in the following 4 groups: (1) 10 normal subjects (control group), (2) 24 patients with paroxysmal atrial fibrillation or flutter (AF) (AF group), (3) 12 patients with left atrial overload without AF (LA group), and (4) 10 patients with right atrial overload without AF (RA group). Original P wave durations showed no significant difference among the 4 groups. Filtered P wave durations (F-PDs) in the AF and LA groups were significantly longer than that in the control group. F-PD correlated significantly with left atrial dimension (LAD). F-PD in AF patients with LAD shorter than 40 mm was significantly longer than that in the control group, but there was no significant difference in F-PD between AF patients with LAD longer than 40 mm and the LA group. Root mean square voltages of original P waves were significantly higher in the LA and RA groups than that in the control group, but in AF patients it did not differ from that in the control group. In conclusion, the signal-averaged P wave is useful to predict atrial fibrillation, but prolongation of F-PD is seen not only in patients with AF but also in patients with LA overload. PMID- 8515571 TI - Angina pectoris caused by dynamic exercise in hypertrophic cardiomyopathy with normal coronary arteries. AB - To evaluate the relationship between angina pectoris caused by dynamic exercise and the time course of heart rate (HR) and hemodynamics during dynamic exercise in 15 patients with hypertrophic cardiomyopathy (HCM) with normal epicardial coronary arteries, the supine ergometer exercise test was performed during cardiac catheterization. The HCM patients were divided into a chest pain group (n = 6) and a no chest pain group (n = 9) based upon the results of the ergometer exercise test. There was no significant difference in the level of ST-segment depression after exercise in both the chest pain and no chest pain groups (-2.1 +/- 0.6 mm vs -2.6 +/- 1.1 mm, NS). Increase in heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) in the early phase of the exercise test was significantly greater in the chest pain group compared with the no chest pain group. These observations suggest that in HCM patients, the occurrence of exertional chest pain has a close relationship with the rapid increase in HR and LVEDP in the early phase of dynamic exercise, but does not have a relationship with the gradual increase in these parameters. PMID- 8515572 TI - Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium 201 myocardial SPECT. AB - Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD > or = 10 and age < 15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD > or = 10 and age > or = 15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD < 10 and age > or = 15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients. PMID- 8515573 TI - Hypertrophic cardiomyopathy with mitochondrial myopathy. A new phenotype of complex II defect. AB - Two brothers, 25 and 19 years old, were affected by asymmetrical hypertrophic cardiomyopathy. The older brother had waddling gait and weakness of the proximal girdle muscles, while the younger had a broad-based gait and weakness of selected limb girdle muscles. EMG exam was myopathic. Serum enzyme, CPK and aldolase were elevated. Histochemical reactions in muscle revealed "core-like" areas, subsarcolemmal rims of mitochondria and lipid accumulation. Succinate dehydrogenase stain showed a lack of activity in both biopsies, with the exception of intrafusal fibers. Microphotometric quantitative measurements confirmed the defect in both biopsies. Biochemical measurements of several mitochondrial enzymes in muscle showed a reduced activity of succinate dehydrogenase (33%) and succinate-cytochrome C reductase (36-47%) which are both components of complex II. On myocardial biopsy lipid and mitochondrial abnormalities were found. This mitochondriopathy represents a new phenotype of partial complex II defect. PMID- 8515574 TI - Reduction of thrombogenicity with argon laser angioplasty. Comparison with balloon angioplasty. AB - Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA. PMID- 8515575 TI - Effect of isosorbide dinitrate infusion on the canine left ventricular force length relationship. AB - Recently, the slope (Ec) of the left ventricular (LV) end-systolic force-diameter (Fes-Des) relationship has been proposed as a new index for assessing myocardial contractility. Using this relationship, the effects of ISDN on LV myocardial contractility were evaluated in 10 healthy adult mongrel dogs. After the intravenous infusion of propranolol and atropine to produce autonomic blockade, the inferior vena cava was gradually occluded for 20 sec to decrease preload while the dogs were kept apneic. The LV diameter was measured by ultrasonic crystals and LV pressure was measured by a micromanometer. After the control measurements, the dogs received intravenous ISDN (1, 5, 10, or 50 micrograms/kg/min), and inferior vena caval occlusion was repeated. Ec and the extrapolated diameter intercept (D0) of the LV Fes-Des relationship were determined for each dog from the end-systolic data. The differences in heart rate between the control state and ISDN infusion at any dose were not statistically significant. The Ec and D0 values also showed no significant changes with ISDN infusion (Ec: 80 +/- 19, 83 +/- 20, 84 +/- 17, 82 +/- 24, and 87 +/- 24 g/cm for 0, 1, 5, 10, and 50 micrograms/kg/min, respectively. D0: 1.38 +/- 0.42, 1.38 +/- 0.40, 1.38 +/- 0.38, 1.34 +/- 0.40, and 1.36 +/- 0.40 cm for 0, 1, 5, 10, and 50 micrograms/kg/min, respectively). These findings suggested that intravenous ISDN did not affect myocardial contractility in the normal in situ canine left ventricle. PMID- 8515576 TI - Cytogenetic effects of CPT-11 and its active metabolite, SN-38 on human lymphocytes. AB - CPT-11, a new camptothecin analogue, has been demonstrated to be a promising antineoplastic agent. Late side effects of carcinogenicity and teratogenicity have been unclear from clinical phase I and II trials. In order to elucidate the carcinogenicity and teratogenicity of CPT-11, we have examined the cytogenetic changes in human peripheral blood lymphocytes induced by CPT-11 and its active metabolite, SM-38. We have also analyzed the correlation between chromosomal damage and acute clinical side effects. When peripheral blood lymphocytes obtained from a healthy donor were exposed to CPT-11, SN-38, cisplatin and mitomycin C, a significant dose-dependent increase of sister chromatid exchange (SCE) was obtained. The SCE frequency per cell cultured with 0.244 nM SN-38 was similar to that cultured with 100 nM CPT-11, 300-500 times the concentration of SN-38. A transient increase in SCE frequency was also observed in the peripheral blood lymphocytes of 11 cancer patients receiving 100 mg/m2 of CPT-11 intravenously, compared with pretreatment values (P = 0.0001). In addition, a significant correlation was observed between the frequency of SCE on day 3 and the degree of decrease in platelet count (P = 0.012). In conclusion, SN-38 might possibly have a high risk of mutagenicity and carcinogenicity; and measurement of SCE values in peripheral blood lymphocytes appears to have a potential application in the clinical prediction of chemotherapy-induced side effects. PMID- 8515577 TI - Recent advances in diagnosis of leukemia. AB - With the development of new technologies in the diagnosis of leukemia, we have modified the method of approaching individual cases. In addition to morphological examination, cytochemistry, immunophenotyping, electron microscopy and cytogenetics are now routinely used for daily practice. Furthermore, various molecular diagnostic methods are being tested, and some are already being used for diagnostic processes. The new technologies have certainly changed the diagnostic approach. When the diagnosis is supported by such multiple diagnostic methods, it is more reliable, reproducible and standardized. The communication among clinical practitioners through accurate diagnosis is valuable from both the therapeutic and prognostic point of view. In this article, the diagnostic method of leukemia is reviewed with an emphasis on practical aspects. Individual details are beyond the scope of this article. Interested readers are referred to the bibliography for more in depth treatment of the various techniques. PMID- 8515578 TI - [Recent progress and trend on study of gastrointestinal hormones]. PMID- 8515579 TI - [Clinicopathological studies on squamous cell carcinoma of the esophagus with esophageal gland-like transformation]. AB - One hundred and seventy cancerous lesions observed among 159 esophagectomised specimens were systematically investigated with histochemical staining methods in addition to the ordinary hematoxylin-eosin staining. About 2/3 of them, 113 lesions, were entirely consisted of the squamous elements, regardless with pearl formation or not, Group 1. On the contrary, the remaining 57 lesions (33.5%) showed foci of esophageal gland-like transformation, Group 2. Those lesions were specified by constituent epithelia with esophageal glandular epithelia-like characteristics; positive for epithelial mucin, secretory component and S-100 protein. Such esophageal gland-like structures could be demonstrated exclusively in cancerous foci penetrated through the lamina muscularis mucosa. Those 113 lesions of the Group 1 did not show any such transformation even by the meticulous examination of the whole lesion by the step sectioning. Those lesions of the Group 2 had a distinct tendency of the perpendicular mural penetration and submucosal extension than the horizontal mucosal involvement, giving rise a characteristic appearance resembling to submucosal tumors. On the contrary, those of the Group 1 showed an ordinary mural extension pattern corresponding to the extent of mucosal involvement, so-to-speak, a typical features of common esophageal cancer. No outstanding difference in biological behaviours could be obviated between two groups so far examined; survival rate, lymph node metastasis, vascular permeation, intraepithelial extension, etc. PMID- 8515580 TI - [DNA synthesis of the mucosa of the gallbladder estimated by bromodeoxyuridine (BrdU)-anti BrdU in vitro method in patients with various gallbladder disorders]. AB - The precancerous state in the gallbladder disorders is an interesting problem in oncology. We studied the DNA synthetic potency by using BrdU-anti BrdU monoclonal antibody in vitro method in patients who underwent cholecystectomy with various gall bladder disorders. The results (BrdU labeling indices; mean +/- SD) were as follows; (1) carcinoma; 4.8 +/- 1.9%, (2) adenoma; 3.3 +/- 2.9%, (3) dysplasia; 3.5 +/- 1.3%, (4) control; 0.4 +/- 0.3%. (5) abnormal pancreatico-choledocho ductal junction; 0.4 +/- 0.2% (the surrounding portions of carcinoma and dysplasia). BrdU L.I. was the greatest in carcinoma and the second greatest in dysplasia and adenoma. It is suggested that dysplasia and adenoma are the precancerous states in gallbladder disorders. While, in the cell types of carcinoma, the L.I. was the greatest in undifferentiated type, followed by tubular type and papillary type was the smallest. PMID- 8515581 TI - [Differential diagnosis of gallbladder diseases by superselective angiography of the cystic artery]. AB - To clarify differential points of angiographic findings, cystic angiograms of 46 patients with various gallbladder diseases were studied. In cases of gallbladder carcinoma, the angiographic findings differed in degree of the depth of cancer invasion and the shape of tumor. Abnormal findings in arterial phase were seen even in some cases of early carcinoma and tumor stains were clearly seen in all cases except for cases of superficial type of early carcinoma. In cases of cholecystitis, the findings on the degree of inflammation and wall thickening of the gallbladder varied. It was important for differential diagnosis between carcinoma and inflammation of the gallbladder to fully understand reciprocal relation of arterial and venous phase of the cystic angiogram. In cases of adenomyomatosis of the gallbladder, dilatation and tortuosity of the branches of the cystic artery and an increase of vascularity in the thickened wall were characteristic. Faint tumor stains were seen in some cases of cholesterol polyps of the gallbladder, which indicates that malignancy should not be diagnosed based only on the presence of such stains. PMID- 8515582 TI - [Effect of cholecystokinin and secretin on insulin binding to rat pancreatic acini and pancreatic cancer cell line AR42J cells]. AB - In order to clarify the interaction of hormones which exert various effects on the exocrine pancreas, we investigated the effect of cholecystokinin (CCK) and secretin on subsequent insulin binding to pancreatic acini and cultured AR42J cells derived from azaserine-induced acinar cell carcinoma of the pancreas. CCK at concentrations of 100pM-10nM inhibited subsequent 125I-insulin binding to pancreatic acini. 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited 125I insulin binding whereas A23187 had little effect, suggesting that the inhibitory effect of CCK is mediated by protein kinase C. On the other hand, 100pM-10nM secretin had no effect on subsequent 125I-insulin binding to pancreatic acini, although higher concentrations of forskolin and 8 bromoadenosine 3', 5'-cyclic monophosphate inhibited 125I-insulin binding. In addition, secretin exerted no potentiating effect on the inhibitory effect of CCK on 125I-insulin binding to pancreatic acini. Based on these results, we further investigated the effect of CCK and TPA on subsequent 125I-insulin binding to AR42J cells. In this carcinoma cell line, inhibitory effect of CCK and TPA on insulin binding was completely abolished. The present results suggest, therefore, that hormonal interaction may play an important role in the regulation of exocrine pancreatic function including acinar cell growth. PMID- 8515583 TI - [Effect of combined use of CR1505 with UFT for the tumor growth of the subcutaneously transplanted pancreatic cancer in the Syrian golden hamsters]. AB - We studied on the effect of combined use of CR1505 with UFT for the subcutaneously transplanted pancreatic cancer induced by BOP (N-nitrosobis (2 oxopropyl) amine) in the Syrian golden hamsters. The tumor growth in the group treated with both CR1505 and UFT was significantly inhibited compared with that in the group treated with only CR1505 or UFT. Labelling index judged by BrdU immunohistochemistry in the group with the combined use was significantly lower than that in the group with the single use. The differences of the body weights and blood analysis were not obscured in the both groups. Moreover, the concentrations of 5-FU and FT207 in tumors were not different between them. These results suggest that a new therapy of the combined use with CR1505 and UFT for the pancreatic cancer should be effective. PMID- 8515584 TI - [A case of Menetrier's disease evaluated by endoscopic ultrasonography]. PMID- 8515585 TI - [Gastrointestinal bleeding due to jejunal metastasis of lung cancer contiguous to an emphysematous bulla]. PMID- 8515586 TI - [A case of granulomatous hepatitis caused by administration of antibiotics]. PMID- 8515587 TI - [An autopsy case of gas-containing liver abscess with pneumatosis cystoides intestinalis]. PMID- 8515588 TI - [A case of retroperitoneal cystic lymphangioma associated with adrenocortical adenoma]. PMID- 8515590 TI - 63rd Annual Meeting of the Japanese Society for Hygiene. April 5-7, 1993. Abstracts. PMID- 8515589 TI - [Endoscopic aspiration mucosectomy using an attached cylinder]. PMID- 8515591 TI - [40 years' studies on environmental hygiene--special reference to environmental physical stimulations]. PMID- 8515592 TI - [Clinical study of tuberculous pleuritis, diagnosed by thoracoscopy using flexible fiberoptic bronchoscope]. AB - Examination by thoracoscopy, using flexible fiberoptic bronchoscope, was performed in 43 patients with pleural effusion according to our reported method. In these patients, 14 cases were diagnosed as tuberculous pleuritis. These 14 cases were investigated with respect to clinical and thoracoscopic findings. Their mean age was 38.1 years, and 11 cases were younger than 50 years old (78.5%). The male:female ratio was 2/1. Clinical symptoms recognised were fever (100%), cough (64.2%), chest oppression (50%) and sputum (35.7%). In 5 cases, gastrointestinal symptoms were recognized such as vomiting, abdominal pain, and diarrhea. Tuberculin reaction was positive in all patients with tuberculous pleuritis on admission. With respect to the thoracoscopic findings of tuberculous pleuritis, yellow-white miliary granulomas were observed on the parietal pleura in 12 cases (85.7%), and this characteristic finding was especially observed at the apex. Biopsy specimens, obtained from these miliary granulomas on the parietal pleura showed histological findings of tubercles. In the other 2 cases, generalized reddening of the entire parietal pleura was observed, with no yellow white miliary granulomas. Biopsy specimens obtained from the reddened lesions on the parietal pleura showed histological findings of tubercles, and these 2 cases were also diagnosed as tuberculous pleuritis. These results indicate that this method may be very useful for the diagnosis of tuberculous pleuritis in patients with pleural effusion. PMID- 8515593 TI - [Clinical analysis of six cases of acute interstitial eosinophilic pneumonia- with attention to radiographic findings]. AB - We have recently observed six patients with acute interstitial eosinophilic pneumonia. All the patients suffered from an acute febrile illness and severe hypoxemia. Their chest films showed diffuse interstitial infiltrates. Kerley's A and B lines and pleural effusions are characteristic and important for the diagnosis of acute interstitial eosinophilic pneumonia, as they are frequently observed. Eosinophilia in peripheral blood was not initially present in any of the patients. Mild to severe eosinophilia was present during their convalescence. Histological examination showed eosinophilic infiltration of the alveolar walls and spaces. Half of the patients improved following treatment with corticosteroids, and the rest of the patients improved without treatment. To make an early diagnosis, this type of eosinophilic pneumonia should always be considered. It is important to recognize the radiographic findings, that is Kerley's lines and pleural changes, noted in this study. It should be noted that the number of eosinophils in peripheral blood has a tendency to be low during the acute phase. PMID- 8515594 TI - [Incidence of fungal isolation in clinical specimens from the respiratory tract]. AB - The incidence of fungal isolation in 711 clinical specimens from the respiratory tract was investigated in 159 patients with pulmonary diseases. Fungi were isolated from 14/19 pharynx swab samples, 246/342 sputum samples, 34/147 bronchial aspirate samples, 18/97 bronchial lavage samples, 4/17 transbronchial lung biopsy samples, and 5/60 plugged catheter brush samples. Contamination by fungi in normal flora was prevented by using an aseptic procedure for sampling specimens from the respiratory tract. The isolation rate of Candida spp. from sputum was 70.0% (C. albicans: 151 strains, C. glabrata: 43 strains, C. tropicalis: 25 strains, C. lusitaniae: 4 strains, C. krusei: 3 strains, C. guilliermondii: 3 strains and C. paraspilosis: 1 strain). The isolation rates of C. neoformans and A. fumigatus from sputum were 6.4% and 8.8%, respectively. Isolated fungi from bronchial aspirate included 12 strains of C. albicans, 6 strains of C. tropicalis, 5 strains of A. fumigatus and 2 strains of C. neoformans. Isolated fungi from bronchial aspirate revealed 6 strains of C. albicans, 2 strains of C. glabrata, 1 strain of C. neoformans and 6 strains of A. fumigatus. The isolation rates of fungi from sputum obtained from patients with pulmonary aspergilloma and cryptococcosis were 66.5% and 50.0%, respectively. The isolation rate of fungi from sputum of patients with underlying diseases was higher than that of patients with no underlying disease. PMID- 8515596 TI - [Clinicopathological study of diffuse panbronchiolitis--with special reference to relationship between the clinical duration and respiratory bronchiolar lesions]. AB - Fifteen autopsy cases of diffuse panbronchiolitis, with clinical disease duration ranging from 2 months to 56 years since appearance of cough and sputum, were analyzed by reconstruction study using serial sections, with particular regard to the respiratory bronchiolar lesions and clinical duration. In addition, proximal bronchi and bronchioles were examined focusing on dilatation, round cell infiltration and goblet cell metaplasia, and peribronchiolar emphysematous lesions were graded according to the degree of alveolar destruction. Morphological changes of the respiratory bronchioles were classified into five types. Active lesions, with lymphoplasmocytic and xanthoma cell infiltration were classified into three types according to the presence and the size of intraluminal granulation tissue. Scar lesions showing marked fibrohyalinous change were classified into two types, those with and without respiratory bronchiolar stenosis. Active lesions decreased and scar lesions increased with clinical duration. Respiratory bronchiolar lesions were distributed almost equally from the upper lobe to the lower lobe. In these fifteen autopsy cases, the total number of respiratory bronchiolar lesions did not vary with disease duration. Emphysematous lesions increased with clinical duration, and showed a relationship to the presence of scar lesions with stenosis. Bronchiolar dilatation was prominent in cases with a long clinical course. Segmental and subsegmental bronchial dilatation were recognized mainly in the middle, lingula and lower lobes, but there was no relationship between clinical duration and bronchiolar dilatation. PMID- 8515595 TI - [Effect of thromboxane A2 (TXA2) antagonists on bronchial hyperresponsiveness induced by intravenous administration of leukotriene C4 (LTC4) in guinea pigs]. AB - Effects of TXA2 antagonists on bronchial hyperresponsiveness induced by intravenous administration of LTC4 in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance, using a formula to exclude the effects of changes in airway wall thickness. With the formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness to histamine. Administration of LTC4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was enhanced by the administration of LTC4. TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the increased ratio of bronchial smooth muscle constriction of LTC4. On the other hand, the antagonists showed no significant effects on airway wall edema by LTC4. These results suggest TXA2 may play a role in LTC4-induced bronchial hyperresponsiveness to histamine. PMID- 8515597 TI - [Detection and identification of tuberculosis by amplification of mycobacterial DNA from clinical cultured samples]. AB - We examined 57 cultured mycobacteria using a method based on polymerase chain reaction (PCR), slot blot hybridization and dideoxy sequencing of nucleotides for detection of M. tuberculosis. Using standard microbiological tests, 34 of 57 specimens were identified as M. tuberculosis and the rest as atypical mycobacteria. Two of 34 specimens that contained M. tuberculosis were not hybridized with a probe specific for M. tuberculosis. These two specimens were identified as atypical mycobacterium by nucleotide sequencing. An atypical mycobacterium specimen that was hybridized with a prove specific for M. tuberculosis was identified as M. tuberculosis using nucleotide sequencing. These results suggest that the approach using PCR and slot blot hybridization for detection of mycobacterium may be more accurate than standard microbiological tests in the rapid and definitive diagnosis of mycobacterial infection. PMID- 8515598 TI - [Interleukin-1 beta production by alveolar macrophages in cases of asbestos exposure]. AB - In order to investigate the role of interleukin-1 beta secreted by alveolar macrophages in the pathogenesis of pulmonary asbestosis, we performed bronchoalveolar lavage on 12 asbestos-exposed subjects and 10 control subjects, and measured interleukin-1 beta secreted by alveolar macrophages. Interleukin-1 beta production was increased in the asbestos-exposed subjects compared to control subjects (3.1 +/- 2.2 ng/ml versus 0.8 +/- 0.4 ng/ml, p < 0.05). The period after retirement was inversely correlated with interleukin-1 beta production (r = -0.67, p < 0.05). We divided non-smoking asbestos-exposed subjects into two subgroups based on the radiographical profusion according to the ILO classification. The advanced group was defined as grade 2 or greater profusion, and the early group was defined as grade 1 or lower profusion. We found higher production of IL-1 beta in the early group than in the advanced group. PMID- 8515599 TI - [Detection of radiation-induced lung injury by 99mTc-DTPA aerosol inhalation method]. AB - We prospectively monitored pulmonary 99mTc-DTPA (diethylene triamine penta acetate) clearance in patients who received chest radiation therapy, in order to determine whether this method allows us to predict the development of radiation pneumonitis. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was used to assess pulmonary epithelial damage. Fifteen nonsmoking patients who underwent radiation therapy were studied. The subjects included 4 patients who had already developed radiation pneumonitis at the time of study, and 11 in whom we prospectively observed 99mTc-DTPA clearance serially during the course of chest radiation therapy. In the 4 patients with pre-existing radiation pneumonitis, the mean k value obtained from the area with infiltration on the chest X-ray was significantly greater than that from the opposite lung (p < 0.02). In the prospective study, 3 out of 11 patients developed radiation pneumonitis. The mean k of the irradiated lung field in the 8 patients who did not develop radiation pneumonitis was unchanged. The mean k value obtained in the 3 patients who did develop radiation pneumonitis increased just before the onset, and further increased when the disease manifested clinically. We conclude that pulmonary 99mTc-DTPA clearance may be useful for predicting the development of radiation pneumonitis. PMID- 8515600 TI - [Pulmonary hemodynamic effects of cold pressor test in patients with chronic lung disease]. AB - Cold Pressor Test (CPT) was applied to patients with chronic lung disease, including primary pulmonary hypertension, and the effects on pulmonary circulation were compared to those on systemic circulation. HR PPA, and TPR showed maximum values at the end of CPT (Time = 0) and recovered to baseline values 5 min after CPT. CO, however, did not change significantly after CPT. PPA and PAR showed maximum values at the end of CPT and then gradually decreased, but still were significantly higher than baseline values at 5 min after CPT. Nifedipine (NFP) reduced the maximum values of both TPR and PAR at the end of CPT. There was significant correlation between PPA change after CPT and baseline PPA value, and NFP decreased the slope of the regression line. These results indicate that cold stimulation induces both systemic and pulmonary vasoconstriction in patients with chronic lung disease, and this pulmonary vasoconstriction was correlated to the baseline pulmonary vascular tone. Moreover, nifedipine may reduce this cold stimulation-induced pulmonary vasoconstriction. PMID- 8515601 TI - [A case of familial antithrombin III variant complicated by recurrent pulmonary infarction]. AB - We present a 36-year-old male who developed pulmonary infarction secondary to antithrombin III variant. He was admitted to our hospital with progressive chest pain and hemosputum. The presence of multiple defects on 99mTc perfusion scan indicated the diagnosis of pulmonary infarction. He had a past history of pulmonary infarction 4 years before this episode as well as a family history of recurrent thromboembolic disease. Through coagulation studies revealed that the concentration of antithrombin III antigen and progressive antithrombin activity were within normal limits, while heparin cofactor activity was decreased markedly. Of 5 people in his family, 4 proved to have low heparin cofactor activity. These data suggest that functional abnormality of antithrombin III seems to be closely associated with pulmonary infarction. PMID- 8515602 TI - [A case of pulmonary asbestosis with slightly increased serum IgE concentration and histopathological changes resembling DIP]. AB - A 68-year-old male presented with cough and sputum. He had suffered from these symptoms for ten years prior to admission. Chest roentgenogram revealed reticulonodular shadows in the lower fields of both lungs. CT scan of the chest revealed an interstitial pattern in the lower field of both lungs. Honeycombing and bullous pattern were also present in the subpleural area. The patient had a history of dust and asbestos inhalation while working as an electrician. Eosinophilia of the peripheral blood and BALF, and a slightly increased serum IgE concentration were noted. Open lung biopsy revealed interstitial fibrosis with intra-alveolar macrophage accumulation and asbestos bodies. The histopathological features resembled UIP and DIP, although DIP is uncommon in pulmonary asbestosis. The slightly increased serum IgE concentration was considered to be an additional effect of asbestos. This is a case of pulmonary asbestosis with intriguing immunological and histopathological features. PMID- 8515603 TI - [A case of rheumatoid arthritis accompanied by repeated pleural effusion associated with rapid tapering of steroid]. AB - A 65-year-old woman was referred to our department because of general fatigue and anorexia for one month. The patient has received anti-rheumatoid therapy with aurothiomalate and bucillamine for the last two years for rheumatoid arthritis diagnosed 11 years earlier. Based on her systemic arthralgia, positive RA factor, and characteristic pleural effusion, the diagnosis of rheumatoid pleural effusion was made and prednisolone was administered. Two weeks later, the pleural effusion had improved. Rapid tapering of the drug over one month resulted in reappearance of pleural effusion. Slow tapering of prednisolone resulted in disappearance of the pleural effusion. One year after discharge, the patient was again referred to our department because of increased arthralgia. Pleural effusion reappeared after similar rapid tapering of the drug. These results suggest that induction of pleural effusion may occur in rheumatoid arthritis patients as a result of rapid tapering of steroids. Tapering of steroids in rheumatoid patients should be performed with care. PMID- 8515604 TI - [A case of T-cell lymphoma showing multiple nodular shadows and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody]. AB - A 42-year-old man, born in Chiba prefecture, was admitted to our hospital because of multiple nodular shadows on chest X-ray film and an elevated titer of human T lymphotropic virus type I (HTLV-I) antibody. The pulmonary lesion was diagnosed as T-cell lymphoma by open lung biopsy. There has been only one previous report of T-cell lymphoma showing multiple nodular shadows on chest X-ray. The elevated titer of HTLV-I antibody strongly suggested that the present case was one of adult T-cell lymphoma. PMID- 8515605 TI - [A case of slowly-growing localized malignant mesothelioma]. AB - We report a case of localized malignant mesothelioma. The patient was a 37-year old male, admitted to our hospital because of a solitary nodular shadow in the right middle lung field noted on chest X-ray. Five years prior to admission, a solitary nodular shadow had been seen in the same area on chest X-ray, and the diameter of the tumor had gradually increased. A transbronchial biopsy specimen revealed proliferation of spindle-shaped tumor cells, suggesting fibrosarcoma. No other lesions were identified as primary foci, so we made the tentative diagnosis of primary pulmonary sarcoma prior performing right upper lobectomy. The resected specimen revealed that the tumor, which partially touched the pleura, contained a number of large and small cystic spaces, and was composed of numerous spindle shaped tumor cells. Some of the tumor cells were immunohistochemically positive for cytokeratin and epithelial membrane antigen, and many mitotic figures were noted. Thus, we made the histopathological diagnosis of localized malignant mesothelioma. PMID- 8515606 TI - [A case of bronchiolitis obliterans organizing pneumonia associated with ulcerative colitis]. AB - A 53-year-old male was admitted to our hospital with fever and chest pain. A chest X-ray film showed infiltrative shadows in the right upper and middle lung field. In spite of administration of antibiotics, the chest X-ray film revealed gradually increasing infiltrates and a new shadow appeared in the left upper lung field. The open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP). There was marked roentgenographic improvement in response to steroid therapy. Very few cases of BOOP associated with ulcerative colitis have been reported. PMID- 8515607 TI - [A case of acute pulmonary hemorrhage and positive anti-glomerular basement membrane antibody in systemic lupus erythematosus]. AB - A 58-year-old woman was admitted with cough, dyspnea on effort and diffuse micronodular and patchy shadows on her chest roentgenograms. Two weeks later, acute pulmonary hemorrhage developed with low levels of complement and positive immune complexes. She was diagnosed as having systemic lupus erythematosus (SLE) with positive anti-nuclear antibody, positive anti-DNA antibody, biologically false positive Wassermann reaction, auto-immune hemolytic anemia and photosensitive dermatoses. In addition, anti-glomerular basement membrane antibody (anti-GBM antibody) was positive in serum, but pulmonary hemorrhage was thought to be secondary to SLE, since the renal biopsy showed lupus nephritis. Cases of SLE with positive anti-GBM antibody are seldom confirmed. It was assumed that the basement membrane of the lung or kidney was damaged first by interstitial pneumonitis due to SLE or lupus nephritis, basement membranes antigens were exposed, with secondary production of anti-GBM antibody. PMID- 8515608 TI - [Successful embolization of bronchial artery in racemose hemangioma]. AB - A 74-year-old male was admitted to our hospital because of hemoptysis. Bronchoscopic examination showed a polypoid lesion in the right middle lobe bronchus. Biopsy of the polypoid lesion caused a massive bleeding. A massive hemoptysis of about 1,200 ml occurred again on the 13th day after biopsy, angiographic embolization of the right bronchial artery was performed successfully. Dilatation, convolution and hypervascularization of the right bronchial artery were observed, and anastomosis with pulmonary artery was seen. The diagnosis of primary racemose hemangioma of the bronchial artery was made. There was no recurrence of hemoptysis 3 years after the embolization procedure. Bronchial artery embolization is an effective method of treatment of hemoptysis due to racemose hemangioma. PMID- 8515609 TI - [Autopsy case of non-invasive thymoma associated with pancytopenia and hypogammaglobulinemia]. AB - A 57-year-old male presented with palpitations and dyspnea on exertion. Examination of the peripheral blood and bone marrow showed pancytopenia with marked red cell aplasia. Hypogammaglobulinemia was also recognized. Chest X-ray and CT showed a mass in the anterior mediastinum. A biopsy showed thymoma. Two months after admission, the patient died of sepsis secondary to worsening pancytopenia and hypogammaglobulinemia. Autopsy showed non-invasive spindle cell type thymoma and a marked decrease of hematogenous cells. Review of the literature indicates that pancytopenia associated with thymoma is resistant to all forms of treatment and its prognosis is poor. PMID- 8515610 TI - [A case of eosinophilic granuloma associated with a brain lesion]. AB - A 32-year-old man was hospitalized due to right pneumothorax. Chest X-ray showed interstitial shadows predominantly in the upper and middle lung fields. Eosinophilic granuloma was diagnosed by transbronchial lung biopsy. He had a history of paraesthesia in the right arm for 6 months prior to the pneumothorax. Initially, head CT showed an iso-dense area enhanced with contrast medium in the left temporal lobe. Two weeks after the onset of paraesthesia, head CT showed an iso-dense lesion surrounded by low density area. Subjective symptoms disappeared in a month, and no abnormalities on head CT were seen at 2 months. It is highly suspected; therefore, that the present case of eosinophilic granuloma was associated with a brain lesion. PMID- 8515611 TI - [A case of hypersensitivity pneumonitis in Pholiota nameko's manufacturer]. AB - A 58-year-old female was admitted to our hospital because of fever and dyspnea on exertion. She has been working in the factory making Pholiota nameko for 8 years. Her chest X-ray revealed diffuse linear and fine nodular shadows in both lower lung fields. Hypoxemia was seen on blood gas analysis. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. Differential cell count of the BAL fluid showed lymphocytosis and CD4/8 was decreased. TBLB specimens revealed bronchioloalveolitis. Precipitins against Trichosporon cutaneum were detected by Ouchterlony method. These findings are compatible with hypersensitivity pneumonitis, and Trichosporon cutaneum may have been causative antigen in this case. Trichosporon cutaneum is often detected in the Japanese summer-type hypersensitivity pneumonitis. This case suggests that Trichosporon cutaneum is one cause of hypersensitivity pneumonitis in workers at factories making Pholiota nameko. PMID- 8515612 TI - [Alveolar type II cells in centrilobular emphysema lesions of human lung--an ultrastructural study]. AB - The lungs studied were surgically resected, mainly for lung cancer. All lungs had centrilobular emphysema. Emphysematous and non-emphysematous areas were identified by dissecting light microscopy. In emphysematous lesions, transmission electron microscopic observation revealed that (1) the shape of type II cells was associated with the changes of alveoli, such as type II cells were flattened in flattened alveolar wall; (2) the cells were cuboidal in the alveolar corner; (3) the number of close contacts between type II cells and interstitial cells was significantly decreased; (4) osmiophilic lamellated bodies in type II cells were normal in number and shape, and that type II cell hyperplasia was observed in the overlapping alveolar walls. These findings suggest that both injury and repair may occur in the alveolar epithelium of emphysematous lesions, and tissue repair may be impaired. PMID- 8515613 TI - [Endoscopic classification of healing process in tracheobronchial tuberculosis]. AB - Out of 404 patients with pulmonary and/or tracheobronchial tuberculosis treated during the last 10 years at Kurume University Hospital and St. Mary Hospital, in 41 patients, who had been histopathologically or bacteriologically diagnosed as having active tracheobronchial tuberculosis, tracheobronchial lesions were examined by use of bronchofiberscope. Most patients were treated by a combination of three antituberculous agents (INH, RFP and SM or EB). In 31 patients out of the 41 patients, broncho-fiberscopic examinations were performed twice or more. We observed the ulcerous lesions of bronchial tuberculosis at various stages of healing, and could classify the ulcerous lesions into the following three stages. Active Stage: stage A; ulcer formation without regenerating epithelium, Healing Stage: stage H; ulcer formation with regenerating epithelium, Scarring Stage: stage S; and no ulcer formation. Only the lesions of stage A were observed before treatment. In many patients during the first and second month of treatment, the lesions were stage A or H. It was found that healing of the lesions of tracheobronchial tuberculosis progressed through the stages A, H, and S, in this order. The smear positive rates in sputum were 88.5% in stage A, 12.9% in stage H and 5.0% in stage S. The culture positive rates in sputum were 88.5% in stage A, 20.0% in stage H, and 0% in stage S. We conclude that at least 3 months were generally required for the healing of tracheobronchial tuberculosis with ulcerous lesion. However, it seems that the period of time for healing of ulcerous lesions is shorter in patients who are treated by aerosol therapy with SM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515614 TI - [Albumin and fibronectin dynamics in an experimental adult respiratory distress syndrome model]. AB - We produced an experimental adult respiratory distress syndrome model by intravenous administration of oleic acid (OA) in 30 dogs (Group I: 10 normal dogs; Group II: 10 dogs with 0.02 ml/kg of OA; Group III: 10 dogs with 0.04 ml/kg of OA; Group IV: 10 dogs with 0.08 ml/kg of OA). Changes in albumin (AL) and fibronectin (FN) in serum and BALF of these dogs were examined. The following results were obtained: 1) Serum values of AL and FN were significantly decreased after OA injection as compared with the baseline values. These changes were not correlated with the severity of pulmonary edema. 2) BALF values of AL and FN were significantly increased after OA injection as compared with the baseline values. Significant linear correlations were found between the BALF value of AL and ELWV, and between BALF value of AL and delta ELWV, [r = -0.682, 0.573 (p < 0.01)]. Significant linear correlations were also found between the BALF value of FN and ELWV, and the BALF value of FN and delta ELWV, [r = 0.722, 0.650 (p < 0.01)]. BALF value of AL increased significantly even with the low OA dose (0.02 ml/kg). Thus in comparison with BALF value of AL after OA injection, BALF value of FN was significantly higher than that in the normal group even when pulmonary edema were severe (Groups III and IV). We concluded that we could estimate the severity of pulmonary edema by measuring BALF value of AL and FN simultaneously. PMID- 8515615 TI - [Estimation of filtration variables in isolated rat lungs for evaluation of pulmonary microvascular permeability]. AB - In order to evaluate the microvascular permeability of donor lungs, we calculated the filtration variables; K (reflection coefficient), simultaneously. For the calculation of filtration variables, the isolated rat lungs were kept in zone three conditions (pulmonary arterial pressure > pulmonary venous pressure > alveolar pressure). We used Krebs-Henseleit solution (K-H) with 6% bovine serum albumin for the perfusate, and maintained perfusion using a constant pressure circuit system. The pulmonary venous and alveolar pressures were maintained at 2.5 and 2.0 cmH2O, respectively, and pulmonary arterial pressure was set so that change in lung weight occurred. We increased both pulmonary arterial and venous pressures by 3 cmH2O simultaneously, and obtained the initial filtration rate. Then we diluted the perfusate with K-H to about half concentration, and obtained the initial filtration rate. We obtained values of filtration variables of K=4.55 mg.min-1.cm H2O-1.g-1], Ppmv=0.59 cmH2O, and sigma =0.617. These values agree with values from previous reports. Since these three filtration variables are interrelated, this method for simultaneous measurement is more accurate than independent measurements. The chief advantages of this method are that it does not require direct measurement of interstitial pressure or collection of lymph fluid, and all variables are obtained simultaneously. Using this method, the vascular permeability of isolated rat lungs, can be estimated. PMID- 8515616 TI - [Combined use of chest X-rays and body mass index to predict pulmonary hemodynamics in patients with chronic obstructive pulmonary disease]. AB - A study was undertaken to determine whether measurements of radiological indices from chest X-rays and body mass index (BMI) were useful in predicting pulmonary artery hypertension. Measurements of the cardiothoracic ratio (CTR) as well as right descending pulmonary artery diameter (RDPA) and BMI were made in 27 patients with chronic obstructive pulmonary disease (COPD). Mean pulmonary arterial pressure (mPA) correlated with CTR, RDPA and BMI. Multiple regression analysis gave the useful equation: predicted mPA = -3.523 + 0.196xBMI + 0.110xCTR + 0.786xRDPA (r = 0.704, p < 0.002). Fifteen patients were found to have pulmonary hypertension, defined as mPA > or = 20 mmHg. The sensitivity of CTR and BMI were 86.7%. The specificity of BMI was 83.3%. These results suggest that the measurements CTR, RDPA and BMI may be useful in screening for pulmonary hypertension in patients with COPD. PMID- 8515617 TI - [Neutrophil chemotactic factor in supernatant from pulmonary fibroblasts stimulated with cytokines]. AB - Fibroblasts are important for maintenance of the structural frame network for most tissues, and they also play an important role in the inflammatory process via production of various mediators. In this study, we demonstrated that pulmonary fibroblasts may participate in pulmonary inflammation by production of neutrophil chemotactic factor (NCF). Pulmonary fibroblasts were stimulated with various cytokines (IGF-1, PDGF, IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF, IFNr). Fibroblasts stimulated with either TNF, IL-1 alpha or IL-beta but not IGF, PDGF, IL-2 or IL-6 demonstrated a kinetic and dose-dependent increase in NCF activity. The NCF activity of crude supernatant was heat-stable and was not changed by anti C5 antibody treatment or ether extraction. Characterization of the NCF activity by gel-filtration using high pressure liquid chromatography showed two active fractions, one with MW greater than 100 kD and the other with MW less than 10 kD. NCF activity in the small molecular weight fraction was demonstrated by inhibition of chemotaxis by addition of anti-IL-8 antibody. These data suggest that cytokine-treated fibroblast-derived NCF may be important in the pathogenesis and expression of a variety of pulmonary disease processes associated with neutrophil accumulation and activation. PMID- 8515618 TI - [Correlation between proportion of BAL cells and ventilatory function in patients with asthma]. AB - The correlation between proportions of cells in bronchoalveolar lavage (BAL) fluid and ventilatory function was examined in 52 patients with asthma. 1. There was no significant correlation between the proportion of BAL lymphocytes and ventilatory function. 2. The proportion of BAL eosinophils correlated to a certain extent with ventilatory function: the values of %MMF, %V50 and %V25 were lower in patients with BAL eosinophils of 10-19.9% than in those with BAL eosinophils below 4.9%, and %V25 value was significantly lower in patients with a high proportion of BAL eosinophils (10-19.9%) compared with those with a low proportion of BAL eosinophils (0-4.9%). However, ventilatory function was not decreased in patients with BAL eosinophils of more than 20%. 3. The values of ventilatory parameters showed a tendency to decrease with increase in BAL neutrophils. The values of all parameters of obstructive ventilatory dysfunction were significantly lower in patients with BAL neutrophils of > 10% than in those with BAL neutrophils < 4.9%. A significant difference between patients with BAL neutrophils > 10% and < 9.9% was found in values of %V50 and %V25, and the values of %V50 and %V25 were significantly lower in patients with a high proportion of BAL neutrophils (> 10%) than in those with BAL neutrophils < 9.9%. These results suggest that the proportion of BAL eosinophils is to a certain extent related to ventilatory function of asthma patients and that the increase in proportion of BAL neutrophils is closely related to a decrease in values of obstructive ventilatory parameters. PMID- 8515619 TI - [Right ventricular visualization by Tl-201 myocardial scintigraphy in chronic obstructive pulmonary disease]. AB - Tl-201 myocardial scintigraphy was performed in 130 patients with chronic obstructive pulmonary disease (COPD) to evaluate right ventricular hypertrophy, and the clinical significance of this method was studied. Tl-201 uptake ratio of the right ventricle, which represents the ratio of total counts of the right ventricle to counts of the administered dose of Tl-201, was higher in COPD, especially in pulmonary emphysema and B type COPD by Burrows classification than in controls. The grade of visualization of the right ventricle by visual assessment (RVV) was marked (+3) in only a few cases and moderate (+2) in many cases (more than 80%) in all diseases except bronchial asthma. The incidences of right ventricular hypertrophy by electrocardiogram, right-sided heart failure and marked dyspnea (Hugh-Jones 4.5) were very low in cases with RVV grade +2 and very high in cases with +3. The grade of RVV was related to the severity of pulmonary perfusion impairment, although in diffuse panbronchiolitis the RVV was relatively slight compared with the impairment of perfusion. May parameters of pulmonary function such as %VC, FEV1.0%, RV/TLC, V25, %DLCO, Raw, delta N2 and PaO2 showed abnormal values in patients with RVV grade of (+2) or (+3) in all diseases except bronchial asthma. In COPD, Tl-201 myocardial scintigraphy seems to be useful for assessment of right ventricular overloading, and for follow-up observation and differentiation between cor pulmonale and right ventricular hypertrophy secondary to cardiac diseases by observing Tl-201 uptake of the lung and left ventricle. PMID- 8515620 TI - [Clinical features of resected patients with lung cancers revealed by computed tomography]. AB - Seven cases of peripheral lung cancers revealed only by computed tomography (CT) were examined in order to study the clinical features and the roentgeno pathological correlation. There were four male and three female cases with a median age of 68 (range 32-79) years. Conventional X-ray films were negative, but the primary tumors were found by CT. The reasons why the primary tumors were overlooked on conventional X-ray films were that two cases had lesions situated in the para-mediastinal area and five cases had vague lesions. CT findings were classified into two groups; infiltrative type with obscure margin and solid type with clear margin. Histologically, the former were revealed to be well differentiated adenocarcinoma and the latter included poorly differentiated adenocarcinoma and large cell carcinoma. Pathological evaluation showed stage I in six of the seven cases. Our study cannot prove whether CT screening will prevent any number of participants from deaths due to lung cancer. However, it is suggested that CT may be superior for early detection of lung cancer as opposed to conventional X-ray. In the future, a more applicable CT system will be required for early detection of lung cancer. PMID- 8515621 TI - [Usefulness of DLco for the early diagnosis of pulmonary involvement in collagen diseases]. AB - Collagen disease are chronic multisystemic disorders affecting many organs. Pulmonary involvement is frequently associated with these collagen diseases. The usefulness of the diffusion capacity of the lung for the early detection of pulmonary involvement was assessed in 182 collagen vascular disease patients. In addition, the clinical characteristics of those patients with pulmonary lesions were also evaluated. Among these, there were 69 cases of chronic rheumatoid arthritis (RA), 39 progressive systemic sclerosis (PSS), 24 systemic lupus erythematosus (SLE), 12 dermatomyositis-polymyositis (DM-PM), 12 mixed connective tissue disease (MCTD), 11 Sjogren syndrome (SS), 9 Behcet's disease (BD) and 6 unclassified connective tissue disease (UCTD). Patients with normal chest X-ray but with pulmonary dysfunction were recognized in 56% of RA, 59% of PSS, 50% of SLE, 50% of DM-PM, 71% of MCTD, 33% of SS, and 50% of BD cases. Moreover, a higher degree of immunological abnormalities was observed in those with pulmonary complications. From these results, we conclude that diffusion lung capacity is a useful index for the early diagnosis of pulmonary involvement in collagen vascular disorders. PMID- 8515622 TI - [Bacteriological and clinical studies in 23 cases of thoracic empyema--the role of oral streptococci and anaerobes]. AB - The bacteriology of empyema fluid and the clinical background of 23 cases from July 1987 through July 1992 were studied. Nineteen cases were male and 4 female, with a mean age of 59.6 years (range; 33 to 84 y.o.). There were 15 cases of community-acquired infection and 8 of nosocomial infection. Acute pneumonia and/or lung abscess developed into empyema in 19 cases. Sixteen cases had associated predisposing conditions, such as diabetes, chronic bronchitis, disorders with dysphagia, and excess alcohol intake. Forty-one strains were isolated from empyema in 22 cases. The predominant organisms, in order of prevalence, were "Streptococcus milleri" group (11 strains), Peptostreptococcus spp. (6), Prevotella spp. (6), Fusobacterium spp. (5) and other viridans streptococci (3). The majority of streptococcal infections, which were primarily caused by "S. milleri" group, were mixed with anaerobes and/or aerobes/facultatives. These results demonstrate that oral streptococci, especially "S. milleri" group, and anaerobes play a significant role as pathogens in empyema. PMID- 8515623 TI - [Case report of metastatic cutaneous angiosarcoma causing bilateral pneumothorax]. AB - The patient was a 72-year-old man who underwent operation for bilateral pneumothorax due to rupture of cystic lung lesions. Two months after the operation, intrathoracic bleeding redeveloped. The patient developed a tumor on his head. Pathological examination of the scalp lesion revealed cutaneous angiosarcoma. A biopsy of thickened pleura showed that the bleeding was due to pleural metastatic angiosarcoma of the skin. The multiple cystic lesions were considered to be metastases of angiosarcoma. We conclude that pneumothorax or hemothorax in the elderly should be differentiated from malignant metastatic lung tumor. Cystic lung lesions should be considered as possible metastatic angiosarcoma from the skin. PMID- 8515624 TI - [A case of pulmonary alveolar microlithiasis]. AB - The patient was a 42-year-old man. When he was a third grade pupil of elementary school, he was diagnosed as having miliary tuberculosis. He was absent from school for 2 years for the treatment of the disease. However, miliary tuberculosis did not improve in spite of 2 years of treatment. At that time he was diagnosed as having pulmonary alveolar microlithiasis. He did not receive any treatment for the following 30 years. Recently, he visited our department because of occasional chest pain. The following tests were performed; chest CT, tomography, respiratory function test, RI test (99mTc bone scintigram and 67Ga scintigram) and bronchoscopy. Bronchoalveolar lavage (BAL) was performed of B5b, and transbronchial lung biopsy (TBLB) of left B5b, B8b, B9b and B10b to make the accurate diagnosis of pulmonary alveolar microlithiasis. This case of pulmonary alveolar microlithiasis with a protracted course of 30 years (in which chest X ray films taken 27 years ago were available) is reported together with a discussion of the literature. PMID- 8515625 TI - [An autopsy case of primary pulmonary malignant lymphoma associated with right pulmonary infiltrative shadow and macroglobulinemia]. AB - We experienced a patient with two peaks of elevated monoclonal IgM and IgA in the serum, and lambda type Bence-Jones protein in the urine. Chest X-ray films showed right pulmonary infiltrative shadow and effusion. The results of the autopsy of this patient revealed infiltration of malignant lymphoma cells in both lungs, but in no other organs. The results of immunohistochemical staining for L26. UCHL-1, IgM, IgA and lambda chain in this case led to the diagnosis of diffuse small cell type. B-cell lambda, IgM type malignant lymphoma. Gene analysis using bone marrow did not reveal any rearrangement bands for the heavy chain, light chain kappa and lambda, or TcR beta genes. Therefore, we concluded that malignant lymphoma cells had infiltrated only the bilateral lungs, causing a rare case of primary pulmonary malignant lymphoma with two monoclonal peaks of increased serum IgM and IgA. PMID- 8515626 TI - [A case of ceftazidime-induced pneumonitis]. AB - We report a case of ceftazidime-induced pneumonitis. A 76-year-old man had been treated with cefotiam for acute pneumonia; however, he developed a high fever. On November 8, 1991, cefotiam was changed to ceftazidime and S-sulfonated human immunoglobulin. The patient showed good improvement. Four days after commencement of ceftazidime therapy, he developed chills, rigors, and high fever, with interstitial infiltrates in the right lung of his chest X-ray. On physical examination, small bubbling and crepitant rales were heard at the right lung. Once ceftazidime therapy was discontinued, he showed rapid resolution of symptoms and marked regression of the pulmonary infiltrates in the right lung of his chest X-ray. In view of the above, ceftazidime-induced pneumonitis was considered to be the diagnosis in this case. To our knowledge, there has been no previous case report of pulmonary hypersensitivity to ceftazidime. Clinicians should be alerted to the possibility of the occurrence of such a complication in patients being treated with ceftazidime. PMID- 8515627 TI - [Five cases of acute pulmonary failure associated with nitrogen dioxide inhalation]. AB - Six men were accidentally exposed to NO2 when they were changing a propeller using a gas burner in the poorly ventilated hold of a ship. All of them were admitted to hospital with shortness of breath and cough. Chest X-ray on admission revealed diffuse, patchy and infiltrative shadows, leading to the diagnosis of pulmonary edema in all five patients. Steroid therapy was effective and followed by a quick recovery in all patients. None developed third phase manifestations characterized pathologically by bronchiolitis obliterans. PMID- 8515628 TI - [A case of piperacillin-induced pneumonitis]. AB - A 43-year-old woman was treated with piperacillin (PIPC) for spiking fever. Although she was afebrile, fever recurred on the 18th day of PIPC administration with progressive dyspnea and diffuse ground glass shadows on the chest X-ray. Bronchoalveolar lavage fluid (BALF) showed marked increase of total cell number and percentage of lymphocytes and a reduction of the ratio of CD4/CD8. Transbronchial lung biopsy (TBLB) specimen revealed interstitial infiltration of lymphocytes and histiocytes with granulomatous lesions. The drug lymphocyte stimulation test (DLST) was positive for PIPC. Based on these findings, the diagnosis of PIPC-induced pneumonitis was made. Recently, the incidence of drug induced pneumonitis has increased, but to our knowledge this is a rare case report of PIPC-induced pneumonitis. PMID- 8515629 TI - [A case of angiosarcoma of the scalp with numerous thin-walled cavitary pulmonary lesions]. AB - A 69-year-old man was diagnosed as having angiosarcoma of the scalp. Under local radiotherapy he developed a left pneumothorax, then a right pneumothorax three weeks later, making treatment difficult. Numerous thin-walled cavitary lesions throughout both lung fields were demonstrated on chest CT scans. The bilateral pneumothorax were probably due to the numerous lung metastases. Despite various treatments, he died of respiratory failure one month after the development of pneumothorax. PMID- 8515630 TI - [Micturition disorders by pelvic floor relaxation]. PMID- 8515632 TI - [Sequential estrogen and radiation therapy for stage C prostate cancer]. AB - Sequential estrogen and radiation therapy was introduced to improve treatment result for stage C of the prostate cancer. Staging operation was performed in order to exclude stage D1 cases at the beginning of the treatment. Twenty of 34 stage C cases have been treated by sequential estrogen and radiation in our hospital between 1980 and 1989 and half of them had actually been done staging operation. An average age was 69.3. Tumor differentiations were distributed to well in 5 cases, moderately in 5 and poorly in 9. The other unknown differentiation case was diagnosed by fine needle aspiration cytology. Previously administered estrogens were DES-DP in 15 cases and others in 5. Total doses of 70 Gy in 35 fractions were sequentially delivered to the prostate, involving if necessary the seminal vesicles over a seven-week period by bilateral 120 degrees pendel using linear accelerator. Radiation field was sized from 6 x 6 to 8 x 8 cm. Estrogens have been continuously administered following radiation in 11 cases. Therapeutic effects upon the prostate were evaluated by digital rectal palpation. Improvement rate and atrophy rate of the primary lesion were 94.4% and 50% respectively. Recurrences were observed in 4 cases and 3 of them recurred within 3 years after initiation of the treatment. Recurred sites were in primary lesion in 2 cases and in bone in two. Five year non-recurrence rate was 81% by Kaplan Meier's method. One of 3 who discontinued hormone administration during or immediately after radiotherapy had local recurrence after 65 months and the other 2 cases died of gastric cancer and unknown cause, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515631 TI - [Serum concentration of type IV collagen in urological cancer--comparison with serum concentration of laminin]. AB - In recent years, it has become clear that various extracellular substrates play an important role in the process of invasion and metastasis of malignant tumors. In a previous study, we reported that the serum concentration of laminin in renal cell carcinoma and prostate cancer is elevated, and furthermore, is remarkably high in patients with metastasis. However, in bladder cancer, this level is elevated only in those with metastasis, indicating that the serum concentration of laminin is useful as a marker for metastasis or clinical progression of the malignant tumor. In the present study, we measured the serum concentration of type IV collagen 7S-domain, which, as laminin constructs the basement membrane, and compared the result with the serum concentration of laminin, to evaluate the clinical significance of the findings. The serum concentration of type IV collagen 7S-domain was not elevated significantly in any tumor type, although the serum concentration of laminin was elevated in patients with renal cell carcinoma, prostate cancer and bladder cancer with metastasis. There were no significant differences in the serum concentration of type IV collagen 7S-domain in any group with metastasis. PMID- 8515633 TI - [Screening of bladder cancer by a combination of transabdominal ultrasonography and urine cytology]. AB - We evaluated the presence or absence of bladder cancer by a combination of transabdominal ultrasonography and urine cytology in 60 patients who had been suspected of having bladder cancer. All patients then underwent cystoscopy, and biopsy or resection if necessary, and 24 patients were diagnosed as having bladder cancer. By the combination of ultrasonography and urine cytology the diagnosis was correct in 23 patients accounting for 96% of sensitivity, and the misdiagnosis was made in only one patient who had undergone BCG therapy for carcinoma in situ but had submucosal invasive bladder cancer. Because of the high sensitivity rate, we believe that the combination of transabdominal ultrasonography and urine cytology should be the first-choice examinations for patients who are suspected of having bladder cancer. PMID- 8515634 TI - [Postoperative results of ligation of crura penis for impotence with corporal veno-occlusive insufficiency]. AB - We performed ligation of the crura penis for 34 impotents with corporal veno occlusive insufficiency without arterial insufficiency and neural dysfunction from October 1987 to April 1991. Ages ranged from 24 to 72 (52.6 +/- 12.7) years old and follow up period was from 1 to 41 (17.7 +/- 12.6) months. For six patients ligation of the crura only was performed, for 22 ligation of the crura and deep dorsal vein (DDV) as well was performed at the same time, and for 6 crural ligation was performed after ligation of DDV. These operations required less than one hour and there were no severe complications. The postoperative results at 1 month were as follows: Excellent (sufficient spontaneous erection was recovered); 18, Improved (complete erection with intracavernous papaverine injection was achieved); 13, and Failure; 3. Erectile function was maintained only in 50% of the 18 pts. graded excellent. Ninety percent of the 31 patients graded either excellent or improved could maintain erectile function after 40 months with papaverine injection. Venous surgeries could not be a primary treatment for correcting the outflow abnormalities (of the veins). So it is conceivable that failure or recurrence could occur during a long follow up period. We concluded that crural ligation was acceptable as the first line treatment for erectile dysfunction due to corporal veno-occlusive insufficiency because of its relative non-invasiveness compared to other venous surgeries. PMID- 8515635 TI - [Indications for urinary drainage in neonates detected in utero]. AB - The routine use of maternal ultrasonography has led to increasing discovery of fetal abnormalities of the urinary tract. It is well known that some of the fetal hydronephrosis improves spontaneously, and that there is non-obstructed type of hydronephrosis. However, some of the infants require the management in the neonatal periods because of the mass effect from the dilated urinary tract, urinary tract infection, or deterioration of the renal function. Herein we report on 103 cases with urinary tract abnormalities detected by the prenatal ultrasonography, and analysed the renal function in the early neonatal periods to determine the necessity of the emergency urinary drainage. 1. Renal function of the normal neonates (control) Seventy four infants without abnormalities of the urinary tract were studied on serum creatinine (SCr) and fractional excretion of sodium (FENa) during the first four weeks of life. The SCr of infants at birth to one day postnatally was almost the same with maternal SCr. In infants with a gestational age of 33-40 weeks it fell steadily and reached the value around 0.6 mg/dl at 1 week after birth. The fall of SCr was significantly slow in infants with a GA of 28-32 weeks. Similarly, the FENa was significantly higher in infants with a GA of 28-32 weeks than in infants with a GA of more than 33 weeks. Glomerulo-tubular balance was maintained as early as 1 week postnatally in the latter group. 2. Infants treated in the neonatal periods Urological management was done on 26 infants (23%) during the neonatal periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515636 TI - [Fertility after treatment for testicular tumor]. AB - Thirty-four patients with stage 1 or stage 2A testicular tumor all survived 5 years after the treatment, whereas eighteen patients with stage 2B or 3 testicular tumor, including only nonseminomatous tumor, had a 5-year survival rate of less than 50%. Spermatogenesis returned to normal in 3 patients surviving 22 months after chemotherapy. Five patients who had undergone retroperitoneal lymph node dissection with division of the inferior mesenteric artery developed impaired ejaculation, whereas 3 patients who had undergone the operation without division of the inferior mesenteric artery had normal ejaculation. In 17 patients with right testicular tumor metastases were found in the para-aortic, paracaval and interaortocaval lymph nodes. On the other hand, in 4 patients with left testicular tumor metastases were limited to the para-aortic nodes. These results indicate that impaired spermatogenesis by conventional chemotherapy is reversible in patients with stage 1 or 2 testicular tumor, and patients with stage 1 tumor or stage 2 tumor with localized para-aortic metastases, not involving the inferior mesenteric artery, should undergo retroperitoneal lymph node dissection without division of the inferior mesenteric artery to preserve postoperative fertility. PMID- 8515637 TI - [Neoadjuvant therapy for prostatic cancer]. AB - Neoadjuvant therapy for prostatic cancer might be important to increase cure rates of the disease and preservability of the organs. There were 43 cases in a period of 1975-1990 in which total prostatectomy were performed after neoadjuvant therapy. According to the clinical stage, there were 14 cases in B, 23 in C, 4 in D1 and 2 in D2. The median duration of neoadjuvant therapy was 4 months. Clinical response of the prostate in 37 evaluable cases was as follows; 6 cases were PR (16%), 12 cases were MR (32%) and 19 cases were NC (52%). Histopathological effect was as follows; 5 cases were grade 0a (12%), 12 cases were grade 0b (28%), 16 cases were grade 1 (37%), 8 cases were grade 2 (19%) and 2 cases were grade 3 (5%). In 2 cases with histopathological effect of grade 3, lymph node metastases were thought to have obviously disappeared. Histopathological effect seemed related to clinical response. In cases given neoadjuvant therapy for less than 2 months, no adequate clinicopathological effect was obtained. Cases that could achieve downstaging were 8; 1 in grade 0a, 2 in grade 1, 3 in grade 2 and 2 in grade 3. These results suggest that neoadjuvant therapy plays an important role in advanced prostatic cancer. PMID- 8515638 TI - [Response of the human neurogenic bladder induced by intramural nerve stimulation]. AB - The detrusor contraction induced by intramural nerve stimulation in human neurogenic bladders was investigated in comparison with control bladders. All the cases with the neurogenic bladder underwent ileocystoplasty in order to resolve intractable incontinence and/or vesicoureteral reflux due to low bladder compliance or severe detrusor uninhibited contraction. 1. The dose-response curve and ED50 value for KCl were not different between neurogenic and control bladders. 2. The response of neurogenic bladders induced by intramural stimulation was significantly stronger than that of control bladders. 3. After application of 10(-6) M atropine remaining contraction of neurogenic bladders was significantly greater than that of control bladders, i.e. 28.4% and 3.7% respectively. However, 10(-6) M tetrodotoxin almost completely inhibited the detrusor contraction in both groups. 4. The subthreshold KCl (5 mM or 10 mM) enhanced the detrusor contractility significantly in control bladders compared to neurogenic bladders. 5. After bathing medium was replaced into Ca-free Krebs' solution, the contractile response was decreased. The contraction of neurogenic bladders in Ca-free solution persisted longer than that of controls. In conclusion, though there was no intrinsic difference in detrusor contractility, contractile response to electrical field stimulation, atropine resistance, enhancement of response by potassium, and contractility in Ca-free solution were significantly different between neurogenic and control bladders. PMID- 8515639 TI - [A study of methicillin-resistant Staphylococcus aureus (MRSA) infection in urological field]. AB - Out of 110 strains of Staphylococcus aureus isolated from 1985 to 1990, isolation rate of methicillin-resistant S. aureus (MRSA) was investigated. Nineteen strains of 59 S. aureus from outpatients and 20 strains of 51 S. aureus from inpatients were determined as MRSA. Isolation frequency of MRSA from inpatients was increasing in the recent two years. Coagulase type, enterotoxin type and production of toxic shock syndrome toxin-1 (TSST-1) were examined in 22 strains of MRSA. Coagulase type II (86%), enterotoxin type C (68%) and TSST-1 positive strain was most dominant. Susceptibility of MRSA to 4 antimicrobial agents were measured, MRSA were sensitive to vancomycin (VCM), arbekacin (ABK) and minocycline, but resistant to flomoxef. Thirty-four patients from whom MRSA was isolated including 20 patients from urine, 13 from pus and 1 from blood, were analyzed clinically. Pyuria was not recognized in some cases in whom MRSA was isolated from their urine. Concomitant polymicrobial infection was frequently noted in those patients with MRSA in their urinary tract. These facts show that the pathogenic role of MRSA in the urinary tract infection was not significant. On the other hand, when MRSA was isolated from pus or blood, serious infections could be caused by MRSA, especially in compromised host. Regarding the treatment in these cases, administration of VCM or ABK was though to be necessary. PMID- 8515640 TI - [Urodynamic evaluation for bladder dysfunction after radical hysterectomy]. AB - Bladder dysfunction after radical hysterectomy and/or radiotherapy for uterine cancer is a serious problem. Its pathogenesis has not been well elucidated. Urodynamic and clinical evaluations were performed in 53 patients; 24 of them underwent radical hysterectomy and postoperative radiotherapy (RH + RT), 13 had radical hysterectomy alone (RH), 7 had modified radical hysterectomy (mRH), 9 had radiotherapy alone (RT). Nine preoperative patients without micturition disturbance were examined, serving as controls. Patients with more than 50 ml of residual urine were only 3 in RH + RT, 2 in RH and 1 in RT. Bladder volumes at maximum desire to void were significantly lower in RT than in controls. Intravesical pressures at maximum desire to void were significantly higher in RH + RT and RH than in controls, but there were no significant differences between mRH or RT and controls. Detrusor compliances significantly decreased after radical hysterectomy and/or radiotherapy. Maximum urethral closure pressures significantly decreased after radical hysterectomy with or without radiotherapy. In RH + RT, 18 patients (75%) of them mainly complained of urinary incontinence. Their functional profile lengths were significantly shorter than in controls. We conclude that the pelvic plexus injury by radical hysterectomy compromise both urethral closure function and bladder compliance. PMID- 8515641 TI - [A study on markers of bone metabolism in patients with non hypercalciuric calcium stone--measurement of gamma-carboxyglutamic acid and hydroxyproline]. AB - Thirty-one patients (26 male and 5 female patients) of non-hypercalciuric Ca stone formers were studied concerning their bone metabolism. We measured plasma free gamma-carboxyglutamic acid, plasma hydroxyproline, urinary free gamma carboxyglutamic acid and urinary hydroxyproline as markers of bone metabolism. Plasma free gamma-carboxyglutamic acid level showed significantly higher in stone formers than normal controls (1.01 +/- 0.37 nmol/ml vs 0.39 +/- 0.13 nmol/ml). But no significant difference were observed in plasma hydroxyproline level (1.99 +/- 0.73 micrograms/ml vs 2.27 +/- 0.92 micrograms/ml), urinary free gamma carboxyglutamic acid (52.0 +/- 17.6 nmol/mg.Cr vs 45.7 +/- 9.8 nmol/mg.Cr), and urinary hydroxyproline (3.87 +/- 2.02 micrograms/mg.Cr vs 3.33 +/- 1.63 micrograms/mg.Cr). In conclusion, these results suggest that abnormality of bone metabolism may be not a primary event in causing stone formation in these patients. PMID- 8515642 TI - [Evaluation of preoperative diagnosis of primary hyperparathyroidism--special reference to normocalcemic cases]. AB - Since the opening of our clinic 117 years before, we have treated 62 cases of primary hyperparathyroidism (PHPT), among which there were 6 cases (1 male, 5 females) whose calcium levels fell within the normal range. However, in all these cases the serum ionized calcium (Ca++) levels and the serum ionized calcium/calcium ratio (Ca++/Ca ratio) were high. Moreover, in comparing them with hypercalcemic patients (56 cases), the serum Ca++ levels were significantly lower, but the (Ca++/Ca ratio) was significantly higher. Also, the excised weight of 606.1 +/- 520.3 mg was significantly smaller than that of hypercalcemic patients, which was 1,967.9 +/- 2,086.3 mg. Preoperative locations showed significantly lower levels in comparison with hypercalcemic patients by all methods including computed tomography (CT), ultrasonography, scintigraphy, and magnetic resonance imaging (MRI). In normocalcemic patients following parathyroidectomy, although the decrease in serum calcium levels was not significant, the serum Ca++ levels and the Ca++/Ca ratio decreased significantly, so that not only are they useful parameters for preoperative diagnosis of PHPT, but they are also considered necessary and indispensable for observation of the post-operative course and judging therapeutic effects including the operation. Based on our study we concluded that in multiple and recurrent stone formers with normal range of serum Ca levels, regardless of the presence or absence of local diagnosis, if the serum Ca++ level and Ca++/Ca ratio are high, existence of primary hyperparathyroidism must be suspected, and adequate treatments should be instituted promptly. PMID- 8515643 TI - [Clinical studies on renovascular hypertension with bilateral renal artery stenosis]. AB - Clinical studies were performed on 7 renovascular hypertensive patients (3 male and 4 female, mean age 50.6 +/- 18.6) with bilateral renal artery stenosis. Duration of hypertension ranged from 2 months to 24 years (mean 6.1 +/- 8.2 years) before evaluation. All had stenosis or occlusion of both main renal arteries or these branches shown by arteriography. In 4 of the 7 patients atheromatous stenosis or occlusion was present; the remaining two had aortitis syndrome and one had fibromuscular hyperplasia. Of the 7 patients operated, two who had both negative renal renin study and ureteric catheterization study; one was failure after bilateral percutaneous transluminal angioplasty (PTA), and another one was improved after axillo-femoral bypass operation. In one patient with positive results of both studies an area of focal cortical atrophy was present in upper part of the left kidney. The patient, therefore, underwent partial nephrectomy the left kidney but failed to have decrease of blood pressure and was subsequently treated with antihypertensive medications. In the remaining four patients operated, two who had both positive renin and catheterization studies preoperatively were cured or improved after PTA in negative side and nephrectomy of positive side kidney. Other two patients with contradictory results of renin and catheterization studies underwent, PTA of the renal artery of the kidney with the highest renin levels. But their hypertension was maintained despite sufficient dilatation of the renal artery and PRA from the contralateral kidney was noted to be markedly increased after PTA. Therefore, nephrectomy of the contralateral nonfunctioning contracted kidney was performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515644 TI - [Metachronous bilateral testicular seminomas. A case report]. AB - A case of metachronous bilateral testicular seminomas on a 36-year-old male is reported. He had a history of right testicular typical seminoma treated with right high orchiectomy and adjuvant irradiation therapy 6 years previously. He returned to our clinic complaining of painless left testicular enlargement in August 1990, and under a diagnosis of testicular neoplasm left high orchiectomy was performed. Histopathological examination revealed anaplastic seminoma. DNA histograms of both testicles revealed almost the same aneuploid pattern. The patient was diagnosed as stage I seminoma, has been followed up closely. Recently genetic factors as human leukocyte antigens (HLA)-A24, B14, DR5 and DR7, have been shown to be important in the development of metachronous bilateral testicular tumors. HLA antigens were determined in our case, and HLA-A24 shown in our case was compatible with the review. PMID- 8515645 TI - [Spontaneous thrombosis of the pampiniform plexus--case report]. AB - Spontaneous thrombosis of the pampiniform plexus is a extremely rare condition, with only 9 cases reported in the literature. We report here a case of this entity and demonstrate that surgical exploration should be indicated to rule out some of these other conditions, such as a tumor of the intrascrotal component, acute scrotum or inguinal herniation. PMID- 8515647 TI - [Midwife on the road--study report from Boras, Sweden]. PMID- 8515646 TI - [Extracorporeal shock wave lithotripsy in a patient with hemophilia B]. AB - We report a successful treatment of extracorporeal shock wave lithotripsy (ESWL) on a renal stone in a patient with severe hemophilia B. The patient was 44 years old man who had suffered left flank colicky pain with gross hematuria. A radiographic study showed a left renal stone, 22 x 14 mm in size. Before treatment, the intravenous administration of 1,000 U of the missing factor IX was tried, which induced the recovery of the prothrombin and partial thromboplastin times to the normal levels. One thousand units of factor IX were infused 30 minute before ESWL and 2,363 shock waves (Dornier MPL-9000) were administered at 17 kV under intravenous anesthesia by pentazocine. After the treatment, ultrasound and CT did not detect any perirenal hematoma. Antihemophilic therapy was continued with 1,000 U of factor IX per 12 hours for 2 days, 1,000 U per 24 hours for the succeeding 8 days and 500 U per 24 hours for the last 7 days. Gross hematuria disappeared on the 3rd day. We could successfully treat a renal stone in a patient with hemophilia. PMID- 8515648 TI - [Nursing and knowledge come closer. Poissy Central Hospital looks for new ways of treatment]. PMID- 8515649 TI - [Experiences in circumcision]. PMID- 8515650 TI - [Dear midwives!]. PMID- 8515651 TI - [Genital infections and their care]. PMID- 8515652 TI - Endothelins: circulating plasma levels and presence in other biologic fluids. PMID- 8515653 TI - Tissue and cell-specific patterns of expression of rat liver and intestinal fatty acid binding protein during development and in experimental colonic and small intestinal adenocarcinomas. AB - BACKGROUND: Mammalian small intestinal and colonic epithelium express members of a multigene family of hydrophobic ligand binding proteins of which liver and intestinal fatty acid binding protein represent among the most abundant intestinal gene products. These proteins are expressed in a cell- and region specific manner and emerge in a temporally distinctive pattern. EXPERIMENTAL DESIGN: We have studied expression of these genes in the small intestine and colon of rats treated with 1,2-dimethylhydrazine since these animals develop a predictable pattern of both small and large bowel cancers. Studies were also undertaken in fetal and neonatal small intestine and colon. RESULTS: There was a 10- and 50-fold decrease, respectively, in mRNA abundance for intestinal and liver fatty acid binding protein in RNA from colon cancers compared with either uninvolved or control RNA. Immunocytochemical analysis revealed decreased staining for both proteins within their normal distribution together with ectopic clusters of cells reactive for liver fatty acid binding protein within colonic tumors. A more striking mosaic of immunocytochemical staining for both liver and intestinal fatty acid binding protein was found in small intestinal adenocarcinomas. Similar mosaic patterns of immunocytochemical staining were transiently detectable in rat fetal small intestine and neonatal colon. CONCLUSIONS: The region- and cell-specific expression of these genes, which may be linked temporally to events in intestinal differentiation, are subject to disruption in a cell-specific manner in the transformed, or dedifferentiated, phenotype. PMID- 8515654 TI - Treatment of murine mucopolysaccharidosis type VII by syngeneic bone marrow transplantation in neonates. AB - BACKGROUND: Bone marrow transplantation (BMT) proved an effective therapy for murine mucopolysaccharidosis type VII (MPS VII) in adult gusmps/gusmps mice with well developed clinical and pathologic characteristics of the disease. MPS VII mice transplanted as adults had a marked decrease in lysosomal storage material in many organs, although not in the skeleton and brain (1). Since untreated newborn MPS VII mice appear normal and have minimal lysosomal storage material detectable microscopically, we postulated that BMT in newborn mice might prevent the subsequent accumulation of storage material. EXPERIMENTAL DESIGN: One-day-old mutant and phenotypically normal mice were exposed to 2, 4, 6 and 8 Gray and then injected intravenously with syngeneic bone marrow cells from homozygous normal females. Transplanted mice were examined biochemically and microscopically at 10 weeks and 10 months of age. RESULTS: Newborn mice receiving BMT lived longer than untreated mutants, had less severe facial dysmorphism, and better mobility. beta Glucuronidase activity in liver, spleen, kidney and brain increased with increasing radiation dose. The secondary elevations of alpha-galactosidase and beta-hexosaminidase observed in MPS VII, were significantly reduced in liver and spleen in all radiation groups. Treated mutants had less histologic evidence of lysosomal storage disease in bones, joints and periarticular tissue as compared with untreated mutants. Neonatal BMT also reduced storage in the leptomeninges, ependyma and retinal pigment epithelium and caused a slight decrease in neuronal storage at high radiation dose. Radiation dose dependent cerebellar and retinal dysplasia and long bone growth retardation was observed when the therapy was initiated in newborn mice but not when the animals were transplanted as adults. CONCLUSIONS: BMT is a more effective therapy for MPS VII when it is performed at birth rather than in adults. Alternate means of ablating host hematopoietic stem cells should be employed as a pretreatment for BMT due to the severe side effects of radiation on newborns. PMID- 8515655 TI - Altered localization of 73-kilodalton heat-shock protein in rat kidneys with gentamicin-induced acute tubular injury. AB - BACKGROUND: The constitutive 73-kilodalton heat-shock protein (HSP73) has been shown to have various essential functions in cells under both normal and stress conditions. In the present study, we observed serial localizations of HSP73 in rat kidneys with gentamicin-induced acute tubular injury. EXPERIMENTAL DESIGN: Sprague-Dawley rats received gentamicin (80 mg/kg/day) for 14 days, and developed acute proximal tubular injury. The intrarenal immunohistochemical distribution of HSP73 was examined by using a specific antibody against HSP73. In addition, HSP73 content in both isotonic buffer- and detergent-extractable renal fractions were measured by immunoblot analysis. RESULTS: After the gentamicin exposure, HSP73 moved from the nucleus to the cytoplasm, and accumulated in granules that were considered to be expressed within enlarged lysosomes in the injured proximal tubular epithelial cells. These granules started to appear from 36 hours after the first gentamicin exposure, enlarged in size until day 12, and gradually diminished after day 18. At day 27, the HSP73 localization pattern returned to that in the normal kidney. Moreover, significantly increased HSP73 protein bands were detected by immunoblot of detergent-extractable fractions from gentamicin treated rat kidneys at from 36 hours to day 15 after the gentamicin exposure. CONCLUSIONS: Our findings suggest that HSP73 is rapidly induced as an insoluble form in injured lysosomes of the proximal tubular epithelial cells during gentamicin-induced acute tubular injury. PMID- 8515656 TI - Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. AB - BACKGROUND: By using a novel experimental system for the study of reactive fibroblast differentiation at the molecular level, we describe the induction of the alpha-isoform of smooth muscle actin by transforming growth factor-beta (TGF beta 1) in human normal breast gland fibroblasts. EXPERIMENTAL DESIGN: The experimental system allowed fibroblasts to plate and remain quiescent and nonreactive but at the same time stay sensitive to environmental cues for more than 2 weeks after explantation. Most important, the biological activity of growth factors and cytokines could be studied without cells entering the cell cycle, thus serving as a model for stromal reactions with little cell turnover. RESULTS: By use of double-labeling immunocytochemistry, isoelectric focusing, two dimensional gel electrophoresis, and fluorography, evidence is presented that the effect of TGF-beta 1 is dose-dependent with a maximal response above 80 pg/ml and a course of 6 days. No other growth factor/cytokine tested (platelet-derived growth factor, interleukin-1, insulin-like growth factor-1, acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, and interferon-gamma) could induce alpha-smooth muscle actin on their own or potentiate the effect of TGF-beta 1. In an inhibitory assay, only basic fibroblast growth factor was found to prevent the action of TGF-beta 1. The relative contribution of TGF-beta 1-like activity to carcinoma cell induced alpha smooth muscle actin in fibroblasts was deciphered using TGF-beta neutralizing antibodies and medium conditioned by two different breast carcinoma cell lines. Conditioned medium elicited a fibroblast response indistinguishable from that obtained with exogenously added TGF-beta 1, and indeed neutralization attributed the entire response to the sole effect of secreted TGF-beta 1-like activity. CONCLUSIONS: These results provide a strategy for the molecular characterization of epithelial-stromal interaction in breast neoplasia. PMID- 8515657 TI - Ultrastructural characteristics of Fc epsilon R-positive basophils in the spleen and bone marrow of mice immunized with goat anti-mouse IgD antibody. AB - BACKGROUND: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen and Fc epsilon R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc epsilon R positive, non-B, non-T cells express virtually all of the capacity of mouse splenic "non-B, non-T cells" to produce interleukin-4 in response to stimulation by cross-linking of Fc epsilon R or Fc gamma R, or by the calcium ionophore, ionomycin. EXPERIMENTAL DESIGN: The present study is a detailed ultrastructural analysis of Fc epsilon R-positive bone marrow cells or Fc epsilon R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc epsilon R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. RESULTS: Basophils represented the majority (90%) of the granulated cells present in the Fc epsilon R-positive splenic non-B, non-T cells or Fc epsilon R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc epsilon R-negative cells sorted from spleen or bone marrow of goat anti-IgD injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc epsilon R-positive and -negative preparations contained rare (< 5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc epsilon R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. CONCLUSIONS: Taken together with data concerning the numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen, and Fc epsilon R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD. PMID- 8515658 TI - Energy restriction that inhibits cellular proliferation by torpor can decrease susceptibility to spontaneous and asbestos-induced lung tumors in A/J mice. AB - BACKGROUND: Energy restriction (ER) inhibits various tumors in mice. A/J mice have a very high incidence of lung tumors, that are correlated with elevated levels of pulmonary cell proliferation in this strain. Using A/J mice, we studied the effects of ER on spontaneous and asbestos-induced lung tumors and on labeling indices in the lung as a proximal marker of susceptibility to lung tumors to obtain better understanding of the mechanism of ER in reducing tumorigenesis. EXPERIMENTAL DESIGN: Experiment 1: A/J female mice were instilled intratracheally with asbestos or titanium dioxide or simple saline at 20 weeks of age. At 21 weeks of age, mice of the ER diet group were switched from the control diet (350 kJ/week) to the ER diet (175 kJ/wk) until sacrifice at 105 weeks of age, whereas mice of the control diet group were continued on the control diet. Experiment 2: A/J female mice were begun on ER or control diets at 6 weeks of age. The control and ER mice were kept at 20 to 22 degrees C, whereas mice of another ER group (ER+I) were kept at 30 degrees C until 24 weeks of age. Body temperatures of these mice were monitored by telemetery. RESULTS: The present ER was shown to suppress the development of both asbestos-induced and spontaneous lung tumors. ER mice were confirmed to become torporfic, whereas control and ER+I mice did not. Labeling indices were reduced by ER in the lung as well as in other organs. The reduction of labeling indices was, however, almost recovered by increasing the housing temperature to 30 degrees C. CONCLUSIONS: ER which reduces cellular proliferation in various organs by torpor was shown to inhibit lung tumors. Inhibition of lung tumors by ER is likely to involve a decrease in cell proliferation. PMID- 8515659 TI - Rapid determination of cell-associated tumor necrosis factor production by flow cytometry. AB - BACKGROUND: Tumor necrosis factor (TNF) is a cytokine implicated in many disease states, including septic shock and transplant rejection. Regulation of TNF production is complex, and under certain conditions TNF is expressed in cells, but not released. Determination of TNF, particularly on cells, may allow more rapid and specific diagnosis of diseases, and provide a better guide to therapy. We developed a method to quickly measure TNF associated with cells using flow cytometric techniques. EXPERIMENTAL DESIGN: RAW cells, a murine macrophage cell line, were stimulated with lipopolysaccharide (LPS) and examined by staining with an anti-murine TNF antibody followed by a fluorescein isothiocyanate FITC-labeled secondary antibody. RESULTS: Different permeabilization protocols showed that treating cells with 0.1% Triton X-100 for 5 minutes provided staining of cells comparable to 0.005% digitonin and 0.1% saponin; however, it was no better than untreated cells. Comparison of fluorescein isothiocyanate, phycoerythrin, and Red 613 fluorochromes showed that fluorescein isothiocyanate was comparable to phycoeryrthrin, but better than Red 613. Multiple experiments demonstrated that LPS-stimulated cells exhibited a 1.3- to 6.8-fold increase in the number of cells staining positively for TNF, as compared with unstimulated cells. Kinetic studies showed that LPS induced cell-associated TNF within 30 minutes, which plateaued between 2 and 4 hours. TNF staining correlated with the appearance of TNF biologic activity associated with the cells and immunoperoxidase staining of cytospin preparations. Cyclosporin A has been reported to inhibit secretion of TNF. LPS-stimulated cells treated with cyclosporin A showed no decrease in TNF staining by either flow cytometry analysis or immunohistochemistry, but there was a reduction of TNF in the culture supernatant. The human macrophage cell line, THP-1 was also tested and showed statistically significant results when comparing control versus anti-TNF antibodies. CONCLUSIONS: Flow cytometric detection of cell-associated TNF represents a relatively rapid and simple method with potential applications in the study of TNF gene expression. This method may be used to detect early TNF production in disease states such as septic shock and transplant rejection. PMID- 8515660 TI - Detection of immunoglobulin gene rearrangement of B cell non-Hodgkin's lymphomas and leukemias in fresh, unfixed and formalin-fixed, paraffin-embedded tissue by polymerase chain reaction. AB - BACKGROUND: The majority of B cell nonHodgkin's lymphomas (NHLs) are composed of a genotypically identical cell population characterized by a unique immunoglobulin (Ig) VDJ gene rearrangement which is customarily documented by Southern blot hybridization analysis of fresh tissue. Sometimes, however, this approach cannot be used because of an insufficient quantity of tissue or the unavailability of fresh tissue. Therefore, alternative strategies should be designed in order to overcome these limitations. EXPERIMENTAL DESIGN: One possible alternative is the identification of Ig VDJ products of normal and neoplastic B cells by polymerase chain reaction (PCR) using mixed oligonucleotide primers recognizing the framework III region or Ig variable heavy chain leader sequences and universal Ig heavy chain joining region (JH) oligonucleotide primers. To determine whether the respective DNA samples are suitable for PCR amplification, control and unrelated genes should also be investigated (exon 5 of the p53 gene). In this study, genomic DNA was extracted from a well characterized panel of 139 human B cell lymphoid leukemias and NHLs derived from fresh (84) and/or paraffin-embedded (55) tissue, 19 normal peripheral lymphoid tissues, 9 Epstein-Barr virus infected lymphoblastoid cell lines and, as negative controls, 11 T cell LLs. Clonal Ig gene rearrangement products were assessed for the presence of a distinct PCR fragment after framework III-JH PCR amplification and electrophoretic separation and by DNA sequencing of the cloned PCR-Ig fragments. RESULTS: Eighty-eight of the 139 (63%) B-NHLs consisting of 53/84 (63%) fresh, unfixed and 35/55 (64%) formalin-fixed, paraffin-embedded samples, exhibited distinct PCR bands. Using this approach we were able to identify a single clonal B cell population mixed with 1,000 nonB cells or 5 polyclonal B cells. There was no difference in the detection of monoclonality among different B-NHL categories. PCR fragments were not identified in any of 27 normal lymphoid tissues or 11 T lymphoid leukemias. To detect a larger number of Ig gene rearrangement products, genomic DNA of 12 B-NHL/lymphoblastoid cell lines were investigated using VH specific leader and JH oligonucleotides by PCR. A single PCR product was obtained in 9 of 12 (75%) cases and their clonality was documented by DNA sequencing of the cloned PCR fragments. The clonality of 11 of the 12 (92%) cases could be demonstrated using both PCR approaches. CONCLUSIONS: Our results suggest that the monoclonality of human neoplastic B cells can be efficiently evaluated by PCR equally well from fresh, unfixed and formalin-fixed, paraffin-embedded tissues. This technique should prove to be a powerful tool in clinical diagnosis and research as well as in the retrospective analysis of archival pathologic specimens. PMID- 8515661 TI - A help for painful osteoarthritis of the knee: "doctor, you sure know where to mash.". PMID- 8515662 TI - Gout: modern management of an ancient malady. AB - If Dr. Sydenham could have benefited from today's therapy, he likely would not have had to endure thirty years of "violent ... torture" that gave birth to his most elegant and classic description of acute gout. The five key points to remember in management of the gouty spectrum are: (1) Establish the diagnosis as clearly as possible or as clearly as seems necessary under the clinical circumstances (i.e. arthrocentesis with crystal analysis to establish diagnosis is not always necessary with reliable patients when septic joint seems highly unlikely). (2) Treat acute attacks with NSAIDs alone or perhaps steroids--or rarely IV colchicine under special circumstances. (3) DO NOT START ALLOPURINOL OR PROBENECID DURING AN ACUTE FLARE OF GOUT--IT MAY MAKE THE EPISODE WORSE. (4) The pattern of disease over time (frequency and severity of attacks) determines whether or not one decides to use an agent such as allopurinol, probenecid, or prophylactic colchicine chronically once a patient is over the acute attack--the mere presence of increased uric acid and a single or rare gouty attack would not usually require any other than the appropriate acute therapy. (5) The presence of visible tophi, uric acid renal calculi and destructive gouty arthritis nearly always warrant uric acid lowering therapy. PMID- 8515664 TI - Rheumatology in South Carolina. PMID- 8515663 TI - Rheumatoid arthritis. PMID- 8515665 TI - Occurrence, extent, and implications of pressure waves during excimer laser ablation of normal arterial wall and atherosclerotic plaque. AB - Ablation of atherosclerotic plaque and normal arterial wall was performed using a Xenon-Chloride Excimer laser with a wave-length of 308 nm and a pulse duration of 115 ns. The light was transmitted via a 600 microns bare fibre and adjusted to an energy density of 3.5J/cm2. The acoustic signals generated by the laser pulse were measured with two types of hydrophones consisting of polyvinylidenefluoride with active diameters of 0.3 mm and 0.5 mm and recorded on a dual channel digital storage oscilloscope using either a 0.5 m coaxial cable or a broadband fibre optic transmission system. Tissue was retrieved from nine cadaver human aortas and macroscopically classified as either normal or calcified atherosclerotic plaque. Histological analysis (Haematoxylin eosin, elastica van Gieson, and immunohistochemical staining) was carried out after the experiments to verify the macroscopic diagnosis and to correlate the acoustic responses with the tissue characteristics. For normal arterial wall, maximum peak pressure was 1.28 MPa +/- 0.85 MPa, rise time 163 ns +/- 43 ns, and pressure increase 8.2k Pa +/- 5.4k Pa/ns. For calcified, atheromatous segments, a maximum peak pressure of 2.02 MPa +/- 1.16 MPa, a rise time of 69.9 ns +/- 25.8 ns, and a pressure increase of 32.3 kPa +/- 21.3 kPa/ns was found. Statistical analysis showed a significant shorter rise time (P < 0.0001) and a higher pressure increase (P < 0.0001) for calcified tissue in comparison to normal arterial wall, whereas maximum pressures alone did not allow a differentiation of tissue characteristics. Several hundred kPa are generated during Excimer laser ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515666 TI - Assessing Photofrin uptake in atherosclerosis with a fluorescent probe: comparison with photography and tissue measurements. AB - The purpose of this study was to assess Photofrin porfimer sodium (P*) concentration in atherosclerotic plaque (ASP) using a fluorescence detector (Fluoroprobe) compared with fluorescent photography and chemical extraction of P*. ASP was created in the aortoiliac segments of Yucatan miniswine by a combination of balloon endothelial injury and 2% cholesterol and 15% lard diet for 7 weeks. At that time, swine were given P* I.V. in one of the following single dosages: Group I, 2.5; Group II, 1.0; or Group III, 0.5 mg/kg. Swine were sacrificed 24 hours later and aortoiliac and control carotid artery segments removed. Fluorescence was determined from these segments using photographic techniques, the Fluoroprobe, and a spectrofluorometer after chemical extraction. ASP were identified in all swine using photography and the Fluoroprobe. The intensity of fluorescence measured with the Fluoroprobe for Groups I to III was 1,098 +/- 524, 471 +/- 337, and 295 +/- 173 units, respectively (P < 0.01). The tissue concentration of P* in ASP from each group was 130.4 +/- 82.7, 10.0 +/- 1.2, and 9.1 +/- 0.6 ng/g, respectively (P < 0.01). There was a linear correlation between the fluorescence intensity measured with the Fluoroprobe and the extracted tissue concentration (r = 0.88, P < 0.0001). This study showed that a fluorescent detector such as the Fluoroprobe accurately detects the uptake of P* into atherosclerotic plaque. PMID- 8515667 TI - Atherosclerotic tissue analysis by time-resolved XeCl excimer laser reflectometry. AB - The temporal modification of XeCl laser pulses reflected from human aorta tissue immersed in saline has been studied. Dynamic tissue reflectivity of both normal and atherosclerotic tissues has been examined for various incident pulse fluences between 0.7 and 6.5 J/cm2. Changes in reflected pulse duration are observed for fluences at or above 2.6 J/cm2 with normal tissue targets and 3.0 J/cm2 with calcified plaque. Such reflected pulse analysis may prove useful in identifying tissue targets for ablation during laser angioplasty. PMID- 8515668 TI - Characterization of pulsed-dye laser-mediated vasodilatation in a rabbit femoral artery model of vasoconstriction. AB - Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation. PMID- 8515669 TI - Comparative study between pulsed and continuous wave lasers for Photofrin photodynamic therapy. AB - A study was conducted in the normal canine esophagus to compare continuous wave (CW) and pulsed laser light for photodynamic therapy with Photofrin (4 mg/kg). Forty-eight hours post-injection, 630 nm laser light (CW light from an argon pumped dye-laser and pulsed light from a KTP/532-pumped dye-laser) was delivered using a 24 mm diameter cylindrical esophageal PDT balloon positioned at either distal or proximal esophagus. A 1.0 cm cylindrical diffuser placed in the center of the balloon delivered 300 J/cm of light at an intensity of 400 mW/cm. Three dogs received CW light proximally and pulsed light distally. Four dogs received CW light distally and pulsed light proximally. The light dose delivered to the esophageal mucosa was measured using three isotropic probes placed on the balloon wall. Laser-induced fluorescence technique was used to compare photosensitizer fluorescence intensities at distal and proximal locations. Similar mucosal light doses and drug fluorescence intensities were verified for sites receiving pulsed or CW laser light. Two days after light delivery, the dogs were endoscoped to evaluate the severity of the lesions. While some response variability was observed among different animals, endoscopic examination of the lesions revealed comparable injury from CW and pulsed light in each subject. The animals were then euthanized and necropsies were performed. Based on the gross and histological examination of the lesions, the CW and pulsed laser-induced injuries could not be distinguished. PMID- 8515670 TI - Evaluation of changes in oxygen tension as indicators of RIF-1 tumor response to Nd:YAG laser heating. AB - Heat-induced oxygen tension changes in RIF-1 tumors in C3H male mice were analyzed in an attempt to correlate these changes with tumor response to Nd:YAG laser heating. A low power, microprocessor-controlled Nd:YAG laser was used to superficially heat 250-300 mm3 tumors to base temperatures of 44, 45, 46, or 48 degrees C for 30 minutes via a flexible 600 microns quartz fiberoptic with a terminating microlens. A glass, Clark-style microelectrode was inserted into the center of each tumor allowing real time measurement of the tumor's oxygenation status before, during, and after heating. Results showed that heating at 44 degrees C caused a greater than 2-fold increase in oxygen tension during heating, while a temperature of 48 degrees C caused a brief initial increase in oxygen tension followed by a decrease to below pretreatment values. There was a significant correlation (P < 0.05) between relative tumor oxygen tension during and post-heating and tumor growth delay. A significant correlation (P < 0.05) was also seen between tumor base temperature during heating and tumor growth delay. It appears from our initial data that single point oxygen tension measurements in small RIF-1 tumors may be useful indicators of this model's response to Nd:YAG laser heating. This result may allow for modification of heating parameters (temperature/time) during treatment to optimize thermal response. PMID- 8515671 TI - Fluorospectral study of the rat brain and glioma in vivo. AB - An animal model of cerebral glioma was utilized by implanting C6 glioma cells into the brains of adult Wistar rats. Once tumors developed to 7-12 mm in diameter, we conducted continuous fluorimetry monitoring of glioma up to 24 hours using a fibre-optic system connected to an intensified multichannel photodetector after an intravenous injection of hematoporphyrin derivative (HPD) into the rats. The intensity of the fluorescence in normal brain reached a plateau 6 hours after intravenous injection of HPD while that in glioma reached a plateau 80 minutes after injection. These fluorescence intensities of glioma, brain adjacent to tumor (BAT), and surrounding normal brain were measured in vivo 24 hours after intravenous administration of 5 mg/kg of HPD. The ratio of fluorescence intensities between glioma and brain was 6.1 while the ratio between BAT and brain was 3.9. There were no obvious differences in shapes between the spectra of the natural fluorescence (autofluorescence) of rat glioma and brain but the intensity of autofluorescence was much weaker in glioma. There are many problems in spectroscopic studies of biological tissues in vivo. It cannot be overemphasized that very strict criteria must be applied in order to get accurate data. Fluorescence from HPD administration may be used to discriminate tumor tissue from surrounding normal brain tissue during operation if the measuring conditions could be kept constant. It is important to understand the photospectral properties of glioma and brain tissue in order to get the most benefits in clinical application of light-induced fluorescence or photoradiation therapy. PMID- 8515672 TI - Water-jet-cooled Nd:YAG laser coagulation of experimental liver metastases: correlation between ultrasonography and histology. AB - To establish the value of ultrasonography in imaging laser coagulation of tumor and surrounding tissue, the relation between measurements on ultrasound and histology was determined in a rat tumor model. A piece of colon carcinoma CC531 was implanted in the liver of 21 Wag/Rij rats; 20 days later, tumors (mean diameter 5.3 mm) were treated with a water-jet-cooled Nd:YAG laser at 10 W and either 150 J, 300 J, 600 J, 1,200 J, 1,700 J, or 2,400 J. Ultrasonography was done just pre- and immediately post-laser treatment. The animals were sacrificed and livers removed for light microscopical evaluation. Depth and width of coagulation were measured directly on ultrasound, and on histological samples by computer-assisted image analysis. Laser treatment did not change the echogenic aspect of the tumor on ultrasound. However, liver damage appeared hypoechoic compared to normal liver. A significant correlation was found between the total size of the lesion on ultrasound and histology (P = 0.015, r = 0.57 for depth; P = 0.012, r = 0.58 for width), suggesting that laser induced tumor destruction may be derived from the amount of surrounding hepatic damage on ultrasound. PMID- 8515673 TI - Injury and adhesion formation following ovarian wedge resection with different thermal surgical modalities. AB - The purpose of this study is to determine the role of bleeding, acute thermal damage, and charring in adhesion formation. Postoperative adhesions were compared following ovarian wedge resection in 48 rabbits using different lasers, electrosurgery, and scalpel. Twelve ovaries were sectioned per modality, in randomized pairs. Acute thermal injury as assessed by histology, bleeding, and charring differed among the modalities used. Adhesions were assessed 4 weeks later, by an investigator completely blinded of the treatment protocol. The adhesion scores were 11.6 +/- 8.0 with pulsed Er:YAG laser; 11.9 +/- 7.5 with scalpel; 8.3 +/- 9.3 with electrocautery; 6.7 +/- 8.8 with a continuous (c.w.) Nd:YAG laser; 5.3 +/- 4.8 with c.w. CO2 laser; 3.1 +/- 2.7 with pulsed CO2 laser; 1.7 +/- 1.8 with pulsed Ho:YAG laser; and 0.8 +/- 1.5 in the control (no resection) group. Ho:YAG, Nd:YAG, and electrocautery were completely hemostatic. Bleeding was minimal with the CO2 lasers. Er:YAG and scalpel caused maximum bleeding, requiring hemostatic measures to prevent exsanguination. Charring occurred with electrocautery, CO2 laser, and Nd:YAG laser. Bleeding and charring correlated with adhesion formation, but the histological depth of thermal damage did not. The Ho:YAG laser is a hemostatic, fiber-optic compatible laser causing significantly fewer adhesions (P < 0.04) than scalpel, electrocautery, Nd:YAG, Er:YAG, and c.w. CO2 lasers. Clinical use of the Ho:YAG laser, and the role of carbonization in promoting adhesions, deserve further study. PMID- 8515674 TI - Scanning electron microscopy and thermal characteristics of dentin ablated by a short-pulse XeCl excimer laser. AB - The interaction of a short pulse XeCl excimer laser radiation with human dentin was investigated. The dependence of surface temperatures and temperature gradients into the treated teeth on laser parameters such as fluence (0.5J/cm2 7J/cm2), pulse repetition rate (1Hz-35Hz), and spot size (0.004cm2-0.12cm2) was studied. Additionally, the effect of fluence and pulse repetition rate on dentin microstructure was studied using scanning electron microscopy (SEM). It is demonstrated that this "cold ablation" excimer laser can result in significant thermal modification in the dentin surfaces. Changes include the formation of melted dentin grains, which uniformly cover the surface and the exposed dentin tubules. Maximum temperatures of the ablated surfaces, however, remained relatively low at most laser parameters used. Also, the immediate neighborhood of the root canal was essentially undisturbed at most laser parameters. These observations suggest that with the appropriate choice of parameters XeCl lasers can be effective in producing surface structures that may prove useful in enhancing bond strength or other applications in dentistry, without exposing tooth pulp to significant temperature elevation. PMID- 8515675 TI - Pump/probe transmission measurements of corneal tissue during excimer laser ablation. AB - Transient changes in the transmission of a 355 nm probe pulse through corneal tissue during 193 nm ArF laser ablation have been examined. A significant decrease in collimated transmission of the probe beam was observed for time delays between 10 ns and 1 ms after the 193 nm laser pulse. At 10 ns delay the collimated probe transmission was 70% of the preablation level. Minimum collimated transmission (40%) was observed at 30 microseconds delay. Transmitted probe examination by both diode array and integrating sphere measurements indicate the observed attenuation is due to scattering of the incident probe beam and not due to absorption. The significant scattering at nanosecond delay times suggests onset of the ablation process during the ArF pulse. Scattering therefore may affect the deposition of the 193 nm radiation in the ablation target. PMID- 8515676 TI - Alteration of argon laser-induced scars by the pulsed dye laser. AB - Ten patients with portwine stains (PWS) with test sites previously exposed to an argon laser were evaluated and subsequently treated with five pulsed dye (585 nm) laser treatments over a 10 month period. Clinical assessments, skin surface texture analyses using optical profilometry, and light microscopic histological evaluations were performed prior to commencement and at the end of the study in all ten patients. A change in the skin texture with return of skin markings approximating those of normal skin measured by optical profilometry was observed in the argon treated PWS skin following pulsed dye laser treatments. PMID- 8515677 TI - Comparison of the flashlamp pulsed dye laser with the argon tunable dye laser with robotized handpiece for facial telangiectasia. AB - This prospective study compares the efficacy, side effects, and patient acceptance of the flashlamp pulsed dye laser (FPDL) with the argon tunable dye laser with robotized handpiece (ATDL/H) for facial telangiectasias. Seventeen adult patients with bilaterally symmetric facial telangiectasias were enrolled. The right cheek on each patient was treated in one session with the FPDL at a fluence of 6.0-6.75 J/cm2 and a spot size of 5 mm. The left cheek was treated at the same session with the ATDL/H at a power of 1 W, a fluence of 26-27 J/cm2, and a hexagonal treatment area of 13 mm (127 individual 1 mm spots grouped mechanically by the handpiece). Patients were evaluated subjectively and by the investigators at 2, 4, and 6 weeks for blistering, swelling, bruising, changes in pigment, scarring, overall efficacy, and patient preference. Average treatment times were 5.4 minutes for FPDL and 9.4 minutes for ATDL/H. Blistering, crusting, and discomfort were completely resolved on both sides by week 2 in all patients. Bruising occurred in all patients with FPDL but had resolved in 62.5% of patients at 2 weeks and 100% at 4 weeks. There was no bruising with ATDL/H. Postinflammatory hyperpigmentation was much more prominent with FPDL but had resolved in 88% of cases by week 6. As rated by the investigators 100% of the FPDL treated areas showed excellent clearing of telangiectasias, compared with 47% of ATDL/H treated areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515678 TI - Re: Roberts-Harry D., laser etching of teeth for orthodontic bracket placement: a preliminary clinical study. Lasers in Surg & Med 12:467-470 (1992) PMID- 8515679 TI - Endogenous and exogenous modulation of gap junctional intercellular communication: toxicological and pharmacological implications. AB - During the evolution of single-celled organisms to multicellular metazoans, a family of highly conserved genes coding for proteins (connexins), which as hexameric units (connexins), has evolved to form intercellular channels (gap junctions). These gap junctions allow ions and small molecular weight molecules to flow between coupled cells, thereby facilitating synchronization of electrotonic or metabolic cooperation. Control of cell proliferation, cell differentiation and adaptive responses of differentiated cells have been speculated to be biological roles of gap junctions. The regulation of these gap junctions can occur at the transcriptional, translational and posttranslational levels. Transient downregulation by endogenous or exogenous chemicals can bring about adaptive or maladaptive consequences depending on circumstances. Stable abnormal regulation of gap junction function has been associated with the activation of several oncogenes. Several tumor suppressor genes have also been associated with the up-regulation of gap junction function. Since gap junctions exist in all organs of the multi-cellular organisms, the dysfunction of these gap junctions by various toxic chemicals which have cell type/tissue/organ specificity could bring about very distinct clinical consequences, such as embryo lethality or teratogenesis, reproductive dysfunction in the gonads, neurotoxicity of the CNS system, hyperplasia of the skin, and tumor promotion of initiated tissue. Understanding how many non-mutagenic chemicals might alter normal gap junction function should form the basis of "epigenetic" toxicology. On the other hand, restoring normal gap junction function to cells which have dysfunctional intercellular communication could be the basis for a new approach for therapeutic pharmaceuticals. PMID- 8515680 TI - Pure FSH alone induces ovulation and subsequent pregnancy in the mouse resulting in fetal development. AB - The role of FSH in inducing folliculogenesis is well established. Recently, the availability of pure FSH has led to a reevaluation of its role in the process of ovulation. Previously, these functions have been examined separately, usually with pregnant mares' serum gonadotropin (PMSG) followed by FSH for ovulation or FSH for folliculogenesis followed by hCG for ovulation. To determine if FSH alone can induce both folliculogenesis, ovulation and establish a functioning corpus luteum without exogenous LH, we injected sexually mature intact mice (CD-1) with either ovine FSH (oFSH, 5 micrograms; < 0.2% LH contamination) or recombinant FSH (RCFSH, 1 IU; devoid of any LH activity) to stimulate folliculogenesis, followed forty-eight hours later by a second injection of the same preparation (oFSH, 15 micrograms; RCFSH, 1 IU, respectively) to induce ovulation. Injected female mice were mated individually with a fertile male. On days 15-17, pregnancy rates and fetal development were obtained for each animal and were compared with controls, mice injected with PMSG (1 IU) followed by hCG (1 IU). oFSH/oFSH and RCFSH/RCFSH results were combined since no statistical significant differences were detected between these groups. The pregnancy rate for the group receiving FSH/FSH (78.3%, n = 23) was higher than that of the PMSG/hCG group (48.3%, n = 27; p = .02). The number of fetuses produced per mouse in animals receiving FSH alone (8.5 +/- 1.1; mean +/- S.E.) also was greater than the controls (4.5 +/- 99; p = .01). We conclude that the ability of these animals to proceed beyond ovulation to implantation with fetal development demonstrates FSH's ability to cause not only follicular maturation and rupture, but also granulosa cell luteinization, further identifying the potentially important role of FSH in the ovulatory process. PMID- 8515681 TI - Allosteric modulation of ligand binding to [3H](+)pentazocine-defined sigma recognition sites by phenytoin. AB - The allosteric modulation of sigma recognition sites by phenytoin (diphenylhydantoin) has been demonstrated by the ability of phenytoin to stimulate binding of various [3H] sigma ligands, as well as to slow dissociation from sigma sites and to shift sigma sites from a low- to a high-affinity state. Phenytoin stimulated the binding of the sigma 1- selective ligand [3H](+)pentazocine in a dose-dependent manner. Stimulation of binding at a final concentration of 250 microM phenytoin was associated with a decrease in the KD. The affinities of the sigma reference compounds caramiphen, dextromethorphan, dextrophan, (+)3-PPP and (+)SKF-10,047 were three- to eight-fold higher, while the affinities of benzetimide, BMY-14802, carbetapentane, DTG and haloperidol were unchanged in the presence of 250 microM phenytoin. The relative sensitivity of sigma compounds to allosteric modulation by phenytoin is not a property of all sigma ligands, and may provide an in vitro basis for distinguishing actions of sigma compounds and predicting sigma effects in vivo. PMID- 8515682 TI - Preventive effect of Spirulina maxima on the fatty liver induced by a fructose rich diet in the rat, a preliminary report. AB - Cyanobacteria Spirulina maxima from Texcoco Lake in Mexico was administered as a 5% component of a purified diet, to Wistar rats together with a high percentage of fructose (60%) and its effect on several lipid fractions of plasma and liver was studied and compared to those of rats fed purified diets containing 60% of glucose or 60% of fructose. A preventive effect of Spirulina maxima on the fructose-induced increase of the liver triglycerides level was observed together with an elevation of the phospholipid concentration in this tissue. On the other hand Spirulina maxima produced a plasma cholesterol level even lower than that observed in the control group. PMID- 8515683 TI - Regional homovanillic acid production in humans. AB - Peripheral plasma levels of homovanillic acid (HVA), the deaminated and o methylated metabolite of dopamine, are often used as an indicator of central nervous system dopaminergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma HVA pool in 60 healthy volunteers. Veno-arterial differences and organ plasma flows were used to quantify the relative amounts of HVA contributed by various sites into the peripheral circulation. Positive arterio-venous HVA gradients were found in the pulmonary, hepatosplanchnic, skeletal muscle and jugular vessels of the normal volunteers. No HVA increment was found in the coronary sinus. The renal circulation was determined to be the principal site of HVA clearance, extracting 27 nmol/min. The regional contributions of HVA were as follows: lungs 21 nmol/min, hepatosplanchnic organs 3 nmol/min, skeletal muscle 3 nmol/min and the brain 4 nmol/min. The pattern of regional HVA production contrasted with that of the deaminated dopamine metabolite, dihydroxyphenylacetic acid, for which the heart was the principal site of production identified. Sixteen patients with chronic congestive heart failure (CHF) and 6 patients with pure autonomic failure (PAF) were also studied to investigate possible effects of sympathetic nervous system overactivity and underactivity on peripheral HVA production and plasma HVA concentration. The resting arterial plasma HVA concentration in CHF was increased approximately 3-fold. Unexpectedly, this was attributable to reduced HVA plasma clearance, not increased HVA production. Total HVA production in PAF was diminished by 40%. PAF patients had normal resting arterial HVA levels, this being accounted for by a 57% fall in the renal plasma clearance of HVA. Acute sympathetic nervous system activation in response to bicycle riding was accompanied by a 34% increase in the arterial concentration of HVA. It can be concluded that HVA is produced at a number of sites throughout the body not renowned for their dopaminergic innervation. Regional HVA production is associated, in part, with the metabolism of precursor dopamine in sympathetic nerves and at a rate which appears to be influenced by sympathetic nervous activity. To obtain an accurate indication of central dopaminergic activity the confounding influences of HVA plasma clearance and peripheral HVA production must be excluded. PMID- 8515684 TI - Somatostatin receptor subtype gene expression in human and rodent tumors. AB - Somatostatin (SRIF) analogues display anti-tumor properties believed to be mediated by specific cell surface somatostatin receptors (SSTR). SSTR subtypes have unique pharmacological properties, including specific GTP-binding protein coupling, ion channel regulation, and cAMP inhibition; therefore, identification of isotypes expressed in tumor cells facilitates current efforts to design potent anti-tumor SRIF analogues. Human and rodent solid, transplantable tumors and tumor cell lines were examined for gene expression of SSTR1, SSTR2 and SSTR3 by reverse transcription of tumor mRNA and subsequent amplification of cDNA by the polymerase chain reaction, using SSTR subtype-specific oligonucleotide primers. SSTR2 mRNA transcripts were observed in all of the tumor cell lines examined. SSTR1 gene expression was seen in several human and rat tumor types, and SSTR3 gene expression observed in two rodent tumor types. SSTR mRNA-positive tumors are expected to possess membrane-bound receptors which could potentially interact with anti-tumor SRIF analogues. PMID- 8515685 TI - Placental transfer of (3H)-GM1 and its distribution to maternal and fetal tissues of the rat. AB - The demonstration that ganglioside GM1 pretreatment reduced the ethanol induced neurobehavioral effects in adult pups exposed to ethanol in utero, prompted study to examine whether GM1 crosses the placenta and penetrates fetal tissues. The present results indicate that 3H-galactose labeled GM1 not only passes the placenta but also served as a substrate for the synthesis of polysialogangliosides, and remained in various tissues up to 48 h after maternal (3H)-GM1 administration. PMID- 8515686 TI - Diurnal variation in plasma ir-beta-endorphin levels and experimental pain thresholds in the horse. AB - Diurnal variation in nociceptive sensitivity and plasma immunoreactive beta endorphin (ir-BEND) concentrations was examined in eight healthy Thoroughbred horses. Pain thresholds, ir-BEND concentrations, rectal temperature, heart rate, respiratory rate and pupil diameter were measured over a 24 hour period. Nociceptive sensitivity was determined using two objective measures of pain: the skin-twitch reflex latency and the hoof withdrawal reflex latency. Significant variation in both nociceptive thresholds and ir-BEND concentrations were noted over the 24 hour period, with elevated pain thresholds observed at 0900 hours and smaller secondary peaks at 1500 hours. Immunoreactive beta-endorphin concentrations were also elevated at 0900 hours. Cardiac rate was high and pupil diameter was largest at 0900 hours. These physiologic changes, along with increased pain threshold, mimic the observed effects of morphine and other mu agonists in the horse. The results of this study suggest that endogenous opioid peptides may modulate pain threshold as well as other physiologic parameters in the horse. PMID- 8515687 TI - Regulation of dietary fat preference: establishing a reproducible profile of dietary fat preference in rats. AB - The mechanism(s) underlying preference for individual macronutrients (particularly fat) in diet are poorly understood. The greatest obstacle in designing experiments to define neurochemical determinants of fat preference lies in our ability to clearly identify animals' macronutrient preference (MP) profile. To this end, we have defined the role of several variables and suggested ways to design better studies to examine the mechanism of macronutrient preference. The results of these studies show that the paradigm used for MP analysis, genetics and age of the animal could clearly affect the MP profile. PMID- 8515688 TI - Protective effect of bifemelane hydrochloride on ischemic hippocampal CA1 neuronal damage in the gerbil: relation to induction of HSP70. AB - A protective effect of bifemelane hydrochloride (BF) on hippocampal CA1 neuronal death in gerbils was investigated following transient forebrain ischemia in relation to the induction of 70-kd heat shock protein (HSP70) and its mRNA. Histological examination showed that the neuronal density of the hippocampal CA1 sector treated with 10 and 30 mg/kg of BF (i.p.) was higher than that of the vehicle (p < 0.05 and p < 0.01, respectively) at 7 days after ischemia. Immunohistochemistry against HSP70 protein and in situ hybridization for the mRNA revealed that the inductions of immunoreactive HSP70 and the mRNA were remarkably reduced and limited in the brain hippocampi treated with BF (30 mg/kg) as compared with vehicle-treated animals. These data indicate that BF possesses a protective effect against ischemic injury to the vulnerable CA1 neurons. The possible mechanisms of the protection are discussed. PMID- 8515689 TI - Effects of testosterone on cholesterol levels and fatty acid composition in the rat. AB - The effects of testosterone treatment on cholesterol levels and its fatty acid components were studied in adult rats. Cholesterol levels increased both in the liver and in the serum of castrated rats. Androgen administration restored the normal values only in the serum. A general decrease in unsaturated and essential fatty acids in cholesterol esters was evident after testosterone administration. In the liver, only the C16:O/C16:1 ratio clearly increased after testosterone administration, which inhibited the delta 9 unsaturation of palmitic acid, but not of stearic acid. In the serum the C16:O/C16:1, C18:O/C18:1, and C18:2/C2O:4 ratios decreased after castration and were restored by testosterone. The results indicate a clear inhibition of delta 9 unsaturation of palmitic and stearic acids, of delta 5 unsaturation and elongation in organs other than the liver. No effect was evident on delta 6 unsaturation. This suggests that fatty acid unsaturations are regulated differently by testosterone in different tissues. For delta 9 unsaturation in the liver, the effect also seems to be substrate dependent. PMID- 8515690 TI - Immune response to opiates: new findings in heroin addicts investigated by means of an original enzyme immunoassay and morphine determination in hair. AB - In the early 1970's, some papers appeared reporting an immune response to opiates in animals treated with morphine and in heroin addicts, but further researches failed to confirm these results in humans. The aim of the present work is investigating with a newly developed enzyme immunoassay the existence of specific antibodies to morphine in a group of opiate chronic users, controlled by means of the toxicological analysis of hair. Twenty five opiate addicts inpatients for detoxication treatments were investigated for the presence of morphine specific antibodies and for the morphine content in hair, as a marker of addiction to opiates. Antibodies to morphine were investigated using an original ELISA method using a morphine-human serum albumin conjugate immobilized into the wells of polystyrene microtiter plates. Morphine determinations in hair were accomplished by a radioimmunologic screening followed by HPLC confirmation of positive results. The group of opiate users, in which all the subjects resulted positive for morphine content in hair, showed in the ELISA test an average D OD% value significantly higher than the control group (p < 0.001); in particular, 16 out of 25 addicts could be classified positive for anti-morphine antibodies, which were identified as IgM. Inhibition studies demonstrated Ka's for morphine ranging from 10(4) to 10(10) M-1 and a high cross reactivity for codeine. The presence of circulating antibodies specific to morphine in chronic users of opiates is strongly supported by the present findings. PMID- 8515691 TI - Joseph Snyder, M.D.: 1993-1994 Med Chi president. PMID- 8515693 TI - Breast cancer: a common concern for patients and physicians. AB - Some critics suggest that far too many surgical breast biopsies are performed in the United States. Meanwhile, malpractice suits are on the rise for physicians' failure to detect breast cancer. This creates a paradoxical situation for many physicians. Should the incidence of performing an invasive procedure that may prove inconclusive outweight the risk to women's health and the possibility of a lawsuit? PMID- 8515692 TI - A memorial to Joseph J. Harrison III. PMID- 8515694 TI - Chronic fatigue cured by nasal surgery. AB - Two cases of severe unexplained fatigue with mid-facial pain and rhinitis are presented. Sinus computerized tomography (CT) findings were minor, but both responded to functional endoscopic nasal surgery with resolution (Case 1) or near resolution (Case 2) of chronic fatigue. Possible mechanisms linking nasal disease and chronic fatigue include reflex etiology and sleep disturbance associated with abnormal nasal airflow. Often not considered by the primary care physician in differential diagnosis of fatigue, chronic sinusitis should be explored as a cause in unexplained cases. PMID- 8515695 TI - Maryland physicians on a humanitarian mission to war-torn Croatia. AB - Six physicians from Maryland, California, and Utah participated in a 10-day humanitarian mission to Croatia. They spent long hours in antiquated operating rooms performing maxillofacial and extremity reconstructive procedures; most patients were young or war-injured males. Though not a third world country, Croatia urgently needs finances to acquire drugs, supplies, textbooks, and equipment. PMID- 8515696 TI - The first American medical school. AB - John Archer, a physician from Harford County, was one of the graduates of the first medical school on American soil-Philadelphia College-in 1768. The names of the initial instructors, including John Morgan, William Shippen, and Thomas Bond, and of the first graduates, including John Archer and Jonathon Potts, are well known to most medical historians. Many of these early American physicians had a deep sense of political commitment, and placed conscience and love of country above their medical practices. PMID- 8515697 TI - Patients' rights in a nursing home. AB - Under state and federal law, nursing home residents have many rights, including the right to be treated with respect, to receive reasonable accommodation to individual needs, to not be abused, to be free from unwarranted restraints, to refuse treatment, and to participate in treatment planning. Physicians need a working knowledge of certain fundamental legal concepts in order to help patients, particularly with regard to withholding or withdrawal of life sustaining treatment. PMID- 8515698 TI - Imaging case of the month. Post-traumatic distal clavicular osteolysis. PMID- 8515699 TI - Diabetes and thyroid disease. PMID- 8515700 TI - Rose red and Prussian blue. PMID- 8515702 TI - Treatment of Lyme disease. PMID- 8515701 TI - Andrew E. Mance, M.D.--poet. PMID- 8515703 TI - John von Neumann. PMID- 8515704 TI - Defining clinical workstation. PMID- 8515705 TI - More on barriers to clinical computing. PMID- 8515706 TI - More on barriers to clinical computing. PMID- 8515707 TI - MIASMA, a Medical Informatics Audience Study Multi-Archive. PMID- 8515708 TI - Incorporating data from dissimilar programs. PMID- 8515709 TI - Radiographs by computer for clinicians. PMID- 8515710 TI - Computer-generated patient handouts. PMID- 8515711 TI - Learning principles as applied to computer-assisted instruction. PMID- 8515712 TI - The brain. 1958. PMID- 8515713 TI - Framemed, a prototypical medical knowledge base of unusual design. AB - Carefully structured medical knowledge can be used for a variety of purposes, including medical records, drug and test ordering, and differential diagnosis. The Framemed system divides medical information into 26 domains and arranges the items in a hierarchical sequence. The knowledge in the system resides in descriptive, relational, and conditional records created by experts in the various domains, who must sign and date each record as it is developed and are entirely responsible for its contents. Formation of the hierarchies requires careful attention to concepts and yields a logical framework for a standardized terminology that is in the public domain. PMID- 8515714 TI - Calculating the severity of salicylate toxicity. PMID- 8515715 TI - The climacteric kaleidoscope: questions and speculations. AB - This call for a review of climacteric research, its present trends and methodologies, is not prompted so much by mounting criticism from many quarters as by personal disappointment. Despite increasing research we have not achieved the understanding which, not long ago, seemed so near: we have sadly failed in convincing women (and their medical advisers) we can help them and, worse, we have 'departmentalized' ourselves from the concurrent scourge of cancer of the breast. It is here suggested that some of these aims, indeed a greater understanding of the place of fertility in female life, may be achieved by a reexamination of biological baselines. It is proposed we look again at the evolutionary strategems protecting the young, enquire into ethological/sexual hominoid relationships and reevaluate the biorhythm of repeated pregnancies. It is especially the latter, culturally so unacceptable in societies in which women limit their families and menstruate, that offers new venues for research. For, once seriously considered, without bias, it may help in devising means by which we can retain our way of life, free of the dangers inseparable from avoidance of pregnancy and loss of the benefits of its hormones. PMID- 8515717 TI - The prevalence of oestrogen replacement therapy in South Australia. AB - OBJECTIVE: To ascertain the prevalence of the use of oestrogen replacement therapy in the South Australian community. DESIGN AND SETTING. Data was collected as part of the South Australian Health Omnibus Survey which involved a clustered, self-weighting, multi-stage, systematic representative area sample of 4608 households in metropolitan and country South Australia. One-thousand and forty seven women over the age of 40 were personally interviewed by trained data collectors. OUTCOME MEASURES: Demographic characteristics, prevalence of current or past oestrogen use, type of oestrogen used, period of use and reasons for using, stopping or never using therapy. RESULTS: Current use of oestrogen replacement therapy is 13.6% and ever use was 24.3%. The highest prevalence of use was in the age group 45-54 years. Use of oestrogen replacement therapy associated with women born in the UK or Ireland, middle income earners, intermediate education, recent visits to a general practitioner, a current relationship, previous hysterectomy and smoking. The commonest period of use for current users was 1-5 years and the longest 30 years. In contrast many past users had stopped within 6 months, usually because of side effects. The commonest reasons for oestrogen use were to alleviate symptoms, 'following hysterectomy' and to prevent osteoporosis. Only 4.3% took oestrogen to reduce the risk of heart attack or stroke. Reasons for not taking therapy were often due to the woman being premenopausal, having no symptoms or ignorance of the therapy. CONCLUSION: Nearly one quarter of women over the age of 40 have used oestrogen replacement therapy. In general there is a perception only of the short term benefits amongst the current users and there is misinformation amongst the non-users. Therapy is often stopped after a very short time because of minor side effects. PMID- 8515716 TI - Physicians' views on hormone therapy around and after menopause. AB - Estrogens and progestins are commonly and increasingly used during and after menopause. We studied Finnish physicians' views of this hormone therapy based on their specialty. A questionnaire was sent to a stratified random sample of gynecologists, internists, general practitioners and nonspecialists (n = 500; response rate 74%). Reported prescription habits and opinions concerning benefits and harms of hormones were asked and compared to current literature. Combined therapy was much more popular than was estrogen alone. One fourth of the physicians said hormones should be preventively given to all or to all those at risk for osteoporosis. Long therapies were accepted by many and for our patient cases hormones were recommended much more commonly than were other medical therapies. Most considered prevention of osteoporosis to be a benefit of combined therapy, but opinions of other benefits and harms varied. Gynecologists had the most favourable opinions and most of them considered hormone therapy very useful; the other physicians' opinions were characterized by uncertainties about hormone therapy and its long term effects. PMID- 8515719 TI - Interferon beta-1B for multiple sclerosis. PMID- 8515718 TI - Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. AB - Doses of 100 mg of micronized progesterone (P) and of 0.5 mg of micronized estradiol (E2) were administered vaginally and orally, respectively, in the early follicular phase of the menstrual cycle in six premenopausal women. In the second cycle, the same doses were administered in the same subjects, orally for P and vaginally for E2. Serial blood samples were collected and the following steroids were assayed by highly reliable techniques: P, E2, estrone (E1), deoxycorticosterone (DOC), 5 alpha- and 5 beta-pregnanolone and the sulfates of E1, E2, and DOC. Circulating P and E2 levels were higher after vaginal than after oral administration, while those of E1 were similar after either route. Metabolites of P (DOC, DOCS and pregnanolone) were higher after oral administration. Concerning estrogen sulfates, E1S concentrations were similar whichever the route, while those of E2S were lower after oral than after vaginal administration. This study has confirmed that metabolism of ingested P and E2 occurs mainly in the intestine. Moreover, P was predominantly metabolized to 5 alpha-reduced derivatives, whatever the route of administration. In view of the metabolic pathways which are operative and of the peripheral plasma levels which were found, the vaginal route appears to be more adequate than the oral one for hormone replacement therapy. PMID- 8515720 TI - Insect venom immunotherapy. PMID- 8515721 TI - Critical observations on neuroblastoma treatment with 131-I metaiodobenzylguanidine at diagnosis. AB - Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration. PMID- 8515722 TI - Malignant epithelial tumours in children: incidence and aetiology. AB - The purpose of this study was to establish the incidence of carcinomas in children, changes in incidence over a 30-year period, and to identify features of possible aetiological significance. A total of 173 cases were identified, but after review of the histopathology, 30 patients were excluded because they were considered to have benign epithelial tumours or malignant tumours of nonepithelial origin. Seven other cases were excluded because pathology material was not available. Overall, in 28% of cases, the diagnoses were changed by pathology review. Thus, 136 children in the West Midlands Region diagnosed 1957 1986 were included, with carcinoid tumours (44) and tumours of skin (22), nasopharynx (14), salivary gland (13), adrenal cortex (13), thyroid (9), large bowel (5), other (16). Excluding carcinoids, the age-standardised incidence rate was 2.4 x 10(6) per year. Male:female ratio was 0.7:1 and 66% were aged > 10 years. Incidence increased from 1.5 to 3.3 x 10(6) per year. Genetic factors predisposing to carcinoma included tyrosinosis, MEN II and III, congenital adrenal hyperplasia and basal cell naevus syndrome. There was a case of Li Fraumeni syndrome and several other patients had relevant family histories. Probable "environmental" causes included antenatal exposure to stilboestrol or hydroxyprogesterone hexanoate, stilboestrol given for premature menarche, neonatal hepatitis and prior radiotherapy. The aetiology of carcinomas in children is multifactorial, both genetic and environmental factors being important. The incidence is increasing. PMID- 8515723 TI - Salivary gland carcinomas in children: a review of 15 cases. AB - Salivary gland carcinomas are rare in childhood. We have reviewed the case records of 15 children aged 3-14 years (median 11) identified from children's tumour registries. Primary sites were parotid: 11, submandibular: 3, and base of tongue: 1. The range of histologies was similar to that occurring in adults. Six were treated by complete excision, with one given post-operative radiotherapy (RT). All six remain disease-free at 2 months to 21 years after completion of treatment. Five were treated by partial or sub-total excision. Four were given post-operative RT, of whom 3 are disease-free at 3 years, 6 months--18 years and 1 lost to follow-up (LTFA). One not given RT developed a local recurrence at 11 months and was given RT and LTFA. Four patients had a biopsy only. Three were treated by RT. One is disease-free at 8 years, one died of metastatic disease at 6 months, and one developed a local recurrence at 11 years and has remained disease-free following salvage surgery. One patient with advanced disease not suitable for RT died 3 months after diagnosis. Complete excision is the treatment of choice. Following sub-total or incomplete excision post-operative RT can prevent recurrence. Careful RT planning is necessary to minimise late effects. PMID- 8515724 TI - Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma. AB - One hundred seventy-three consecutive cases of medulloblastoma recorded in the Manchester Children's Tumour Registry from 1954 to 1989 were studied. After review of case notes, X-rays, and health surveys the clinical outcome and incidence of congenital anomaly was determined. A previously unreported association with Rubinstein Taybi syndrome was found. Evidence of a genetic syndrome or congenital anomaly was found in 6.4%. These figures provide further evidence of the higher-than-expected incidence of congenital abnormalities. PMID- 8515725 TI - Ten-year survey of the intellectual deficits in children with acute lymphoblastic leukemia receiving chemoimmunotherapy. AB - Effects of chemoimmunotherapy, including cranial irradiation for central nervous system (CNS)-directed therapy, on children with acute lymphoblastic leukemia (ALL) were investigated. Fifty-five children with ALL in continuous complete remission (> 5 yr) and without evidence of current or past CNS diseases were evaluated in this retrospective study. Using standard measures of intelligence (IQ), we repeatedly (1-4 times/person; mean 2.1 times) evaluated IQ in the cohort of patients for the mean follow-up time of 9.7 yr, ranging from 5.4 to 15.8 yr. Fifty-five patients received the total number of 118 IQ testings and 40 patients received them more than twice. Patients were examined periodically at intervals of 1.4 to 10.0 yr (mean 4.8 yr) following diagnosis. Most of the published studies dealt with single IQ testing, and long-term follow-ups were not enough to assess the consequent IQ change. This report confirms and extends the previous findings: decreased IQ was related to age at diagnosis and irradiation (< 5 yr of age at diagnosis), irradiation-examination interval, and female sex. Further long term follow-up study will be needed in these groups, since their IQs are still on the decline even after 10 yr of diagnosis. PMID- 8515726 TI - Phase II trial of etoposide and cisplatin in patients with refractory and relapsed non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8351. AB - A phase-II study was conducted by the Cancer and Leukemia Group B (CALGB) in patients with refractory and relapsed non-Hodgkin's lymphoma (NHL) to assess the activity of the combination of etoposide and cisplatin. Sixty-five patients were entered on study, and 51 patients were evaluated for this report. The treatment regimen consisted of etoposide, 80 mg/m2 IV daily times 5 and cisplatin 20 mg/m2 IV daily times 5, repeated every 21 days. All patients had failed 1-3 prior chemotherapeutic regimens, had measurable disease, and had a performance status of 0-2. In the 51 evaluable patients, there were 4 complete responses (8%) and 12 partial responses (23%), for an overall response rate of 31% (95% Cl: 19%, 46%). In addition, 15 patients (29%) had some improvement in disease and 6 (12%) had stable disease. Failure-free survival for the 51 eligible patients was 40% at 3 months, 23% at 6 months, and 15% at 1 year. Significant toxicity was observed with this regimen. Severe neutropenia occurred in 20 patients (39%), severe anemia in 8 patients (16%), and severe thrombocytopenia in 18 patients (35%). One patient died of infection. Severe neurotoxicity (1) and hemorrhage (3) were also seen. The etoposide, cisplatin combination is active in NHL; however, in this dose and schedule their combined activity is only minimally better than published reports of etoposide alone. Further studies of related combinations are under evaluation by the CALGB. PMID- 8515727 TI - Association of malignancy and Langerhans' cell histiocytosis: report of three cases. AB - Among 44 children with Langerhans' cell histiocytosis (LCH) seen at the Pediatric Department of the A.C. Camargo Hospital, Sao Paulo, Brazil, three developed malignancy, two before and one after the diagnosis of LCH. Malignancy could be attributed to treatment in one of the three children. Whether the cancer in the other two children represents a chance association of the two processes or is treatment-related, is unknown. PMID- 8515728 TI - Acute lymphoblastic leukemia in Noonan syndrome: report of two cases. AB - Only two cases of Noonan Syndrome (NS) associated with tumor have previously been reported. The authors describe two new cases of NS with acute lymphoblastic leukemia (ALL), which were part of a series of 370 consecutive ALL untreated patients. PMID- 8515729 TI - Langerhans' cell histiocytosis presenting with the superior vena cava syndrome: a case report. AB - A case of Langerhans' cell histiocytosis confined to the mediastinum and presenting with de novo superior cava syndrome is reported. The causes of superior vena cava syndrome in childhood are discussed as is the importance of obtaining pathologic diagnosis prior to initiating therapy. PMID- 8515730 TI - Development of hypertension in neuroblastoma during therapy: a case report. AB - A case of stage 4 neuroblastoma that developed excessive hypertension on day 120 of chemotherapy is presented. The tumor initially had responded well to chemotherapy; however, while the tumor mass decreased, plasma and urine catecholamines and the blood pressure increased. The plasma concentrations of noradrenaline, adrenaline, and dopamine increased to 26.4, 1.8, and 36.2 micrograms/l, respectively. The profile of catecholamine metabolites changed: on day 150 of therapy, noradrenaline, adrenaline, and dopamine levels were increased, whereas HVA and VMA levels were decreased when compared to day 1 of therapy. The only residual neuroblastoma tissue visible on MIBG scintigraphy on day 150 of treatment was a metastasis in the left tibia which was irradiated with 24 Gy. The adrenaline concentration in the left femoral vein was twice as high compared to the right femoral vein. A treatment, possibly radiation-associated tumor cell alteration resulting in a different catecholamine production, is discussed. PMID- 8515731 TI - Another face of medicine. A report from Russia. PMID- 8515732 TI - The University Hospital. Will new strategies keep it in the game? PMID- 8515733 TI - Fetal alcohol syndrome and fetal alcohol effects. The University of Minnesota experience. AB - Fetal alcohol syndrome (FAS) describes a set of physical and neurologic defects that occur in the newborn as a direct result of maternal alcohol consumption. We report on a review of a series of patients seen at the University of Minnesota Hospital and Clinic (UMHC) who were identified as having been exposed to alcohol in the prenatal period. Of 46 patients, 38 were found to have FAS, and seven were found to have a less severe set of abnormalities termed fetal alcohol effects (FAE). This series at UMHC demonstrated many shocking characteristics. The average IQ of the children with FAS was under 70. Every child with FAE had significant hyperactivity and attention deficit. And nearly every child in this study was in foster care or an adoptive home. This review reveals the devastating problems victims of FAS and FAE inherit. PMID- 8515734 TI - MMA peer review program to monitor quality of care. AB - The MMA believes its peer review program is fundamental to organized medicine's desire to monitor the profession while simultaneously improving the quality of care provided to Minnesota patients. The association also recognizes the need to assist outside organizations with peer review. The overall goal of the peer review program will be to assure the public that the MMA is willing and able to address public complaints and organizational concerns regarding physicians who do not comply with accepted practice and professional ethics. Physicians interested in participating in either the internal or external peer review program should submit a letter detailing their experience in peer review activities, describing their professional experience, and listing their eligibility or board certifications. The MMA will be contacting interested and qualified physicians in the near future to organize the committees responsible for peer review. PMID- 8515735 TI - Protecting physician assets from litigation. PMID- 8515736 TI - So someone wants you to join an integrated service network.... PMID- 8515737 TI - Let marketplace regulate specialization. PMID- 8515738 TI - HCMS combats abuse on all fronts. PMID- 8515739 TI - Imported cholera associated with a newly described toxigenic Vibrio cholerae O139 strain--California, 1993. PMID- 8515740 TI - Smoking cessation during previous year among adults--United States, 1990 and 1991. PMID- 8515741 TI - Availability of comprehensive adolescent health services--United States, 1990. PMID- 8515742 TI - Salmonella serotype Tennessee in powdered milk products and infant formula- Canada and United States, 1993. PMID- 8515743 TI - Update: hantavirus infection--United States, 1993. PMID- 8515744 TI - [Cloning and expression of determinants of Bacillus anthracis protective antigen in Escherichia coli, Bacillus subtilis, and Bacillus anthracis cells]. AB - A determinant for a protective antigen (pag) of Bacillus anthracis STI has been cloned. Its expression in Escherichia coli, Bacillus subtilis and Bacillus anthracis cells has been studied. The hybrid plasmids were obtained carrying the different fragments of the gene. The plasmids pPA2 and pPA3 having the 3'-end fragment of pag deleted (the size of 1 kb) still code for a part of protective antigen preserving the immunological and protective properties. PMID- 8515745 TI - [Extrachromosomal genetic elements of Clostridium botulinum. I. Plasmids of toxigenic and atoxigenic strains of Clostridium botulinum type A]. AB - Plasmid profiles in fifteen toxigenic and six nontoxigenic strains of Clostridium botulinum type A were investigated. The electrophoretic patterns of nucleic acids from the bacterial lysates were shown to vary in relation to the mode of bacterial cells lysis and the stage of microbial population growth. Two toxigenic strains harbour a unique 3.9 MD plasmid, five strains have a plasmid of about 6 Md and seven other strains carry an 11.5 Md plasmid. The nontoxigenic derivatives of two toxigenic strains harbouring a 6 Md plasmid have lost this extrachromosomal element. The analysis of the derivatives has not indicated the 6 Md plasmid to be connected with bacteriocin production or antibiotic resistance in Clostridium botulinum. Nontoxigenic variants of three other strains possess an 11.5 Md plasmid similar to their toxigenic parents' one. One of the studied toxigenic strains harboured no plasmids, as well as its nontoxigenic derivative. The functions of all studied plasmids remain unknown. Physical maps of the 11.5 and 6 Md plasmids were constructed on the basis of restriction analysis. The obtained results can be used for identification and differentiation of Clostridium botulinum strains and in further molecular biological experiments with this organism. PMID- 8515746 TI - [Features of expression of the pertussis toxin operon under the control of its own and heterologous promotors in Bordetella bronchiseptica cells]. AB - Expression of the cloned operon encoding the pertussis toxin synthesis under the control of operons own vir-dependent promoter or vir-independent promoter of Escherichia coli origin was studied. Proteins produced by the recombinant strains have been characterized. The pertussis toxin operon was shown to express under the control of both homologous and heterologous promoters in Bordetella bronchiseptica cells. Use of the lac-promoter increases the yield of produced toxin twofold. Copy number of operon in the cell does not influence the level of toxin production. The synthesized protein can be transported into the culture medium. The biological and physico-chemical properties of the protein are similar to the ones of the natural pertussis toxin. Bordetella bronchiseptica strain producing the toxin with decreased toxic activity has been obtained. Thus, a simple system for cellular expression of the toxin operon was constructed in Bordetella bronchiseptica. It permits one to construct new strains producing nontoxic derivatives of the pertussis toxin for construction of nonreactogenic vaccines. PMID- 8515747 TI - [Development of a method for identifying bovine and human types of mycobacteria using the polymerase chain reaction]. AB - An express method has been elaborated for identification of human and bovine species mycobacteria in the polymerase chain reaction. The high specificity of the technique and simplicity of material preparation for research make the experimental procedure simple and quick, permitting one to identify Mycobacterium tuberculosis and Mycobacterium bovis directly in pathogenic material. PMID- 8515748 TI - [Development of new generation of vaccine against pertussis, cholera, botulism, tetanus, and diphtheria toxins]. PMID- 8515750 TI - [Use of aminazine for obtaining isogenic variants of Yersinia pestis strain EV76 with a different set of plasmids]. AB - A method was elaborated for elimination of plasmids from the plague microbe by aminazine. A set of isogenic derivatives of the vaccine strain Yersinia pestis EV76 with different plasmid profiles has been obtained. PMID- 8515749 TI - [Insertion mutants of the vaccinia virus. The effect of inactivating E7R and D8L genes on the biological properties of the virus]. AB - The integrative plasmids with the expressive marker gene for beta-galactosidase were constructed for insertional inactivation of nonessential genes E7R and D8L of vaccinia virus located in the central region of the viral genome. Inactivation of the D8L gene in the strains WR and LIVP results in smaller viral plaques in the culture of chicken embryo cells, decreases the viral ability to propagate in mouse brain and has no effect on the size and character of damage in intracutaneous infection of rabbits. Inactivation of E7R gene did not affect the known biological properties of the virus. The existence of the nonessential genes in the central region of the viral genome, inactivation of which does not result in viral attenuation, can be used for increase of antigenic activity of the live attenuated vaccines. PMID- 8515751 TI - [Diagnosis of mycoplasma infections using directed amplification]. AB - Test systems for rapid detection of mycoplasmas in biological samples have been elaborated on the base of the polymerase chain reaction (PCR). Amplification of the conservative rDNA sequences was used for testing of cell cultures for mycoplasmal contamination. Mycoplasma pneumoniae detection system has been developed based on amplification of the species-specific DNA sequences. Inversions of some repeated sequences in the Mycoplasma pneumoniae genome make it possible to run the PCR with a single primer. The revealed spacer length polymorphism for 16S-23S rDNA operons can be used in the mycoplasmas identification. PMID- 8515752 TI - AAEM case report #26: seventh cranial neuropathy. AB - A 25-year-old man with acute, bilateral facial palsies is presented. He had a lymphocytic meningitis, history of tick bites, and lived in an area endemic for Lyme disease, which was ultimately confirmed by serology. Electrodiagnostic investigation included facial motor nerve study, blink reflex and electromyography of facial muscles, which were indicative of a neurapraxic lesion on the right and an axonopathic lesion on the left. The clinical course was consistent with these findings as the right side fully recovered and the left remained plegic. The clinical features of Lyme associated facial neuritis are reviewed, as is the electrodiagnostic evaluation of facial palsy. PMID- 8515753 TI - Mechanoreceptors in human myotendinous junction. AB - The sensory-nerve-ending system of 40 myotendinous junctions of human palmaris longus and plantaris muscles was studied histologically. All the known four types of nerve endings were identified. The Ruffini corpuscles could be found in equally small numbers (one to five) in both the muscular and tendineal sites of the junction. Also the free nerve endings were distributed equally on both sites. The Pacini corpuscles were frequent in the tendineal site (six to 14), but rare in the muscular site (one to three). The Golgi tendon organs were, in turn, frequent in the muscular site (nine to 12) but rare in the tendineal site (one to four), respectively. Within the muscle and tendon parts of the junction, the distance between two mechanoreceptors was always more than 250 microns and the receptor distribution was homogeneous. Further studies are needed to give functional explanation for these anatomic findings. PMID- 8515754 TI - Motor unit estimation: reproducibility of the spike-triggered averaging technique in normal and ALS subjects. AB - Reproducibility of the spike-triggered averaging technique of motor unit estimation (MUE) was assessed in biceps-brachialis muscle in 10 normal subjects and 15 subjects with amyotrophic lateral sclerosis (ALS). MUE was calculated by dividing the compound muscle action potential by the mean amplitude of 15 surface motor unit potentials (S-MUPs) of low recruitment threshold. Averaged MUE values in normal subjects were higher than in ALS subjects, with few values overlapping. Differences between test and retest MUE values were not significant for either subject group. The relative differences between test-retest values were 45.3% for normal subjects and 32.6% for ALS subjects. Correlation coefficients between test and retest values were low (r = 0.07) for normal subjects when influential outlying points were removed, and higher (r = 0.65) for ALS subjects when individuals with MUE values within the normal range were removed. The higher correlation of test-retest MUE values in ALS subjects compared to normal subjects may be due to a greater probability of resampling among the smaller number of motor units in ALS subjects. In summary, the reproducibility and technical aspects of the spike-triggered averaging technique are similar to those reported for other MUE techniques. PMID- 8515755 TI - Immunohistochemical characteristics of polymyositis in patients with HTLV-I associated myelopathy and HTLV-I carriers. AB - The immunohistochemical characteristics of polymyositis in patients with HTLV-I associated myelopathy (HAM) and HTLV-I carriers were studied. Infiltrating cells were predominantly T cells and were not different from in the control group. All specimens contained positively staining muscle fibers for MHC class I antigens, but class II antigens were also expressed in some muscle fibers in 1 patient with HTLV-I-negative polymyositis, 3 patients with HTLV-I-positive polymyositis, and all 5 HAM patients with polymyositis. Expression of the neural cell adhesion molecule was lowest in the HAM patients. These findings may suggest a different immune environment in polymyositis with HAM. PMID- 8515756 TI - Carnitine palmitoyl transferase deficiency in malignant hyperthermia. AB - The activity of carnitine palmitoyl transferase, an enzyme that catalyzes the transport of long-chain acylcarnitines into mitochondria, was quantitated in EB virus-transformed lymphoblasts from 7 patients with susceptibility for malignant hyperthermia. Immunoreactive enzyme protein was also measured using an enzyme linked immunosorbent assay. Cell lines derived from patients with carnitine palmitoyl transferase deficiency of muscle and from normal individuals were used as positive and negative controls, respectively. One patient with malignant hyperthermia had a deficiency in the enzyme activity which was comparable with that of the known carnitine palmitoyl transferase deficient patients. This individual's lymphoblasts were also deficient in immunoreactive enzyme protein. All of the remaining patients with malignant hyperthermia were deficient only when the backward assay for carnitine palmitoyl transferase was used for quantitation. It is likely that a subset of individuals with a malignant hyperthermia phenotype have a primary deficiency of carnitine palmitoyl transferase and that others have a milder enzyme deficiency secondary to the primary defect in malignant hyperthermia. PMID- 8515757 TI - Giant somatosensory evoked potentials in a patient with the anterior spinal artery syndrome. AB - We studied a previously healthy 25-year-old woman with the anterior spinal artery syndrome, a rare thoracocervical myelopathy with multiple potential etiologies. Quantitative and clinical sensory examination showed dissociated loss of pin prick and temperature discrimination below the level of the lesion, with normal light touch, vibratory, and position sense. Magnetic resonance imaging was consistent with cervical spinal cord infarction. Median SEPs showed normal Erb's potential with absent spinal N13- and normal scalp N20- latency. Tibial SEPs showed normal lumbosacral responses and normal scalp P30- latency. Both median and tibial nerve stimulation produced cortical responses of unusually large amplitude (median 38 microV, tibial 17 microV). We hypothesize that large SEP amplitudes in this patient resulted from loss of anterolateral inhibitory influences on the dorsal column-medial lemniscal system. PMID- 8515758 TI - Purification of human muscle satellite cells by flow cytometry. AB - To purify satellite cells directly from human muscle biopsies, we have developed a method based on size separation of dissociated cells by flow cytometry. Immediately after tryptic dissociation of human muscle biopsies and elimination of erythrocytes, microscopic observation and flow cytometry analysis of cell suspensions revealed two populations of cells differing in size and nucleocytoplasmic ratio. Clonal cultures of these two cell types with a manual procedure demonstrated that only the small cells were myogenic satellite cells. Flow cytometry-sorting and analysis of the small cell population showed that (1) all sorted cells contained desmin immediately after dissociation and plating; (2) more than 98% of the cells expressed the 5.1.H11 epitope after 2 weeks of proliferation in culture; and (3) 90% of the sorted cells were able to form myotubes when cultivated at low density or in clonal cultures. Thus, human muscle satellite cells can be directly purified from human muscle samples using flow cytometry. PMID- 8515759 TI - Muscle fiber conduction velocity changes with length. AB - While recording activity from individual muscle fibers by single fiber EMG (SFEMG), stimulated either through their axons or directly, the length of the recorded muscle fiber was changed--stretched or made shorter--by manipulating the recording needle or by passive joint movements. This resulted in significant changes of latency corresponding to an increase in propagation velocity on shortening of the muscle fiber and to a slowing of its lengthening. The maximum increase in velocity was estimated to 33% and slowing to about 22%. These length dependent changes of muscle fiber propagation velocity are suggested to contribute to the supernormal phase of propagation velocity recovery function and to be responsible for an important part of the myogenic, interdischarge interval dependent, jitter. PMID- 8515760 TI - KANDID--an EMG decision support system--evaluated in a European multicenter trial. AB - KANDID is an advanced EMG decision support system dedicated to the support of the clinical neurophysiologist during EMG examinations. It has facilities for test planning, automatized and structured data interpretation, EMG diagnosis, explanation, and reporting. In a prospective European multicenter field trial, the agreement levels between clinical neurophysiologists and KANDID's diagnostic statements were measured under ordinary clinical EMG practice. KANDID was assessed in 159 individual patient EMG examinations by nine clinical neurophysiologists at seven different EMG laboratories. The reasoning of KANDID was considered understandable for the examiners in 80-90% of cases. The agreement level for the electrophysiological states of muscles and nerves between KANDID and the individual examiners was, on average, 81%. The corresponding diagnostic agreement with KANDID was, on average, 61%. A pronounced interexaminer variation in the agreement level related to the different EMG centers was observed. All Danish and Belgian examiners agreed with KANDID in more than 50% of their cases with regard to the EMG diagnosis, while the English examiners were in agreement with KANDID in 50% or less of their cases. These differences were possibly due to differences in epidemiology, examination techniques, control material, and examination planning strategies. It is concluded that it is possible to transfer systems like KANDID out of their development sites and apply them successfully if they can be locally customized by the clinical end users via editors. PMID- 8515761 TI - The rigid spine syndrome: a vacuolar variant. AB - The rigid spine syndrome encompasses a number of disorders. We report 7 males and 2 females with this phenotype and a single, not previously reported, nosology. The salient muscle histological features were autophagic vacuoles, vacuoles containing capillaries, muscle spindle swelling, and type I fiber predominance. Disease onset was before age 6 years in all patients. Inheritance was probably autosomal recessive as siblings were affected in two families. Pulmonary function tests showed severely restricted ventilation, 3 patients required nocturnal ventilatory assistance, 2 patients had cor pulmonale, and mitral valve abnormalities were common. Serum CK levels were moderately elevated. EMG studies showed evidence of an active, chronic myopathy. The mean motor unit potential duration was statistically significantly shorter compared to controls in the triceps and anterior tibial muscles. Single fiber EMG "jitter" and evoked potential studies were normal. PMID- 8515762 TI - Transcranial cortical stimulation in syringomyelia: correlation with disability? AB - Central motor conduction times were studied using transcranial magnetic stimulation in 17 patients with syringomyelia. Central motor conduction time (lower-limb pathway) was prolonged or responses were absent in 44% of stimulations. When results were compared with clinical findings and magnetic resonance tomography, only a weak correlation was found. Transcranial magnetic stimulation is thus of limited value for diagnosing and monitoring the course of syringomyelia. PMID- 8515763 TI - Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support. AB - We, retrospectively, examined the clinical course, decline in pulmonary function, and requirements for ventilatory assistance in 54 patients with Duchenne-type muscular dystrophy (DMD) who were followed in the muscle disease ward of the National Hospital in Kagoshima, Japan, over the past 20 years. The percentage of the predicted vital capacity (%VC) declined in relation to age and stage of disease. Most patients required assisted ventilation when the %VC fell below 10%. Twenty patients were treated with a negative pressure chest respirator. Six of these died at the mean age of 23.2 years after being on the respirator for a mean period of 18 months. Fourteen patients are surviving at a mean age of 23.5 years after being on the respirator for a mean period of 39 months. PMID- 8515764 TI - Latex hypersensitivity following exposure to gloves during electromyography. AB - A case of a 7-year-old boy with myelodysplasia who developed a local acute hypersensitivity reaction after exposure to latex gloves during electromyography is presented. Anaphylaxis from latex gloves has been recently reported, especially in patients with myelodysplasia. Allergens from rubber gloves can be introduced under the skin during EMG and could cause local or systemic acute hypersensitivity reactions. Electromyographers should elicit a history to rule out rubber allergy and use vinyl gloves if suspicion of allergy exists. PMID- 8515765 TI - Height and nerve conduction. PMID- 8515766 TI - Single motor unit H-reflex in motor neuron disorders. PMID- 8515767 TI - Myasthenia gravis and vitiligo. PMID- 8515768 TI - Physiological assessment of endoscopic surgery for carpal tunnel syndrome. PMID- 8515769 TI - A family with multicore disease. PMID- 8515770 TI - Coexistence of amyotrophic lateral sclerosis and Werdnig-Hoffmann disease within a family. PMID- 8515771 TI - Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). AB - Immunization with the first identified Plasmodium falciparum merozoite surface protein (MSP-1) protected monkeys from an otherwise fatal infection. The question of whether the high degree of diversity in MSP-1 among parasite clones will be an impediment to its development as a vaccine candidate needs to be resolved. We have aligned all published sequences, identifying errors, resequencing a portion of one parasite clone, and identifying probable duplicate sequences of four pairs of parasite clones. The sequences are displayed in a fashion that facilitates the study of variation and its potentially diverse origins. The original dimorphic sequences described by Tanabe et al. have been modified to include only common sequences throughout the entire gene. The extension of the dimorphic region to the 5' end of block 3 brings into question the involvement of intragenic crossover as the major mechanism generating allelic diversity. Additional diversity developed from point mutations and recombination in certain regions of the gene. The regions of variability and conservation should serve as a data base for planning vaccine trials. PMID- 8515772 TI - Comparison of pore-forming peptides from pathogenic and nonpathogenic Entamoeba histolytica. AB - Similar to the findings obtained with pathogenic Entamoeba histolytica, nonpathogenic isolates were found to kill mammalian cells in vitro, and cell extract caused pore formation in liposome membranes. A pore-forming peptide termed APnp was isolated from a nonpathogenic isolate using the schedule developed for the purification of APp or amoebapore, the homologous peptide of the pathogenic isolate HM-1:IMSS. Compared to APp, the specific activity of APnp in pore formation was 60% lower. cDNA sequencing indicated 95% identity of the primary structures of APnp and APp, and secondary structure predictions revealed a high degree of similarity. Notably, a glutamic acid residue at position 2 of APp is in APnp replaced by proline, which shortens one of the two amphipathic alpha-helices considered crucial for the pore-forming function. This structural divergence of the two peptides might explain the difference in their pore-forming activities. PMID- 8515773 TI - A Trypanosoma brucei gene family encoding protein kinases with catalytic domains structurally related to Nek1 and NIMA. AB - Using polymerase chain reaction technology we cloned a Trypanosoma brucei gene fragment that has a deduced amino acid sequence with a high degree of homology to protein kinase catalytic domains. This clone detects two genes by genomic Southern analysis. These genes, nrkA and nrkB, share a 97% nt sequence homology over their 1.3-kb coding regions. NrkA encodes a 48-kDa protein which possess all 11 protein kinase homology regions. The 279-aa N-terminal catalytic domain has highest homology with Nek1, a bifunctional kinase, and NIMA, a protein serine/threonine kinase. Both alleles at the nrkB locus in T. brucei strain IsTAR 1 encode a truncated protein kinase catalytic domain due the presence of a premature termination codon. However, the TREU667 strain is heterozygous at the nrkB locus, encoding one truncated and one full-length molecule. NrkA and NrkB possess multiple phosphorylation site motifs. Both nrk transcripts are constitutively expressed during parasite development. PMID- 8515774 TI - Identification and characterization of a myosin heavy chain gene (mhcA) from the human parasitic pathogen Entamoeba histolytica. AB - The mhcA gene from the human pathogen Entamoeba histolytica was identified using the polymerase chain reaction. It is a single copy gene expressed as a 6.4-kb mRNA. The deduced MhcA protein sequence is highly similar to myosin II from both Dictyostelium discoideum and Acanthamoeba castellanii. The globular head domain of MhcA contains the specific regions involved in ATP binding, actin binding, and interaction with myosin light chain. The tail domain is organized in an alpha helical coiled coil structure, which suggests that MhcA is an alpha-fibrous protein. The coiled coil is interrupted by two prolines indicating that like other myosins, either from smooth muscle or from non-muscle cells, the tail of MhcA folds twice on itself. In addition, MhcA presents sequence similarities with the heavy chain phosphorylation sites of smooth and non-muscle vertebrate myosins. PMID- 8515775 TI - Stable transformation of Trypanosoma brucei. AB - We have further analyzed parameters affecting stable transformation of Trypanosoma brucei. Linear DNA was much more efficient than circular DNA and in the vast majority of transformants analyzed the plasmid DNA had inserted into the chromosomes by homologous recombination. The presence of non-homologous (vector) DNA at one or both ends of linear constructs inhibited transformation efficiency. Less than 1 kb of homologous flanking sequence was sufficient for efficient targeting of a marker gene into the tubulin gene array. When transformants with a single neomycin phosphotransferase (neo(r)) gene replacing a beta-tubulin gene were selected for higher levels of G418 resistance, the neo(r) gene was amplified and spread through the tubulin gene cluster. The additional neo(r) gene copies were adjacent in the tubulin gene array and were added to the array rather than replacing beta-tubulin genes. These results are compatible with asymmetric post replication recombination (unequal sister chromatid exchange) as the mechanism for neo(r) gene amplification. Starting with a circular construct containing the neo(r) gene between tubulin intergenic regions, we obtained a single transformant that maintained the neo(r) genes as an extrachromosomal plasmid. We show this plasmid to consist of a circular pentamer of the input construct. All other attempts to derive a shuttle vector that replicates extrachromosomally in T. brucei were unsuccessful. Our experiments extend previous observations suggesting that T. brucei has a strong preference for chromosomal insertion of exogenous DNA by homologous recombination. PMID- 8515776 TI - Molecular structure of a Toxoplasma gondii dense granule antigen (GRA 5) associated with the parasitophorous vacuole membrane. AB - The P21 antigen of Toxoplasma gondii, defined by the monoclonal antibody TG17 113, has been described as a dense granule component, secreted in the parasitophorous vacuole during host cell invasion. The present work reports the cloning of the gene encoding the P21 antigen, for which we propose the name GRA 5. A cDNA library was screened with a rat antiserum raised against an HPLC fraction enriched in the P21 antigen. cDNA clones encoding GRA 5 were selected by antibody selection on the recombinant proteins. All these clones were incomplete at the 5' end. The 5' fragment of the longest cDNA clone isolated by this first screening was used as a probe in secondary screenings of cDNA and genomic DNA libraries. A genomic fragment containing the P21 gene and nearly full-length cDNAs have been isolated and sequenced. The gene encoding GRA 5 is 834 bp long and does not contain any intron. The deduced amino acid sequence of an open reading frame encoding 133 amino acids perfectly matched that of 5 peptides microsequenced from the native antigen. A N-terminal hydrophobic region was found to possess the characteristics of a signal peptide of 25 amino acids. A second hydrophobic domain, bordered by two hydrophilic regions strongly suggests a transmembrane region. This molecular structure is supported by ultrastructural studies showing the association of the P21 antigen with the parasitophorous vacuole membrane. PMID- 8515777 TI - Expression of Plasmodium falciparum lactate dehydrogenase in Escherichia coli. AB - A Plasmodium falciparum gene is described which encodes lactate dehydrogenase activity (P. falciparum LDH). The P. falciparum LDH gene contains no introns and is present in a single copy on chromosome 13. P. falciparum LDH was expressed in all asexual blood stages as a 1.6-kb mRNA. The predicted 316 amino acid protein coding region of P. falciparum LDH was inserted into the prokaryotic expression vector pKK223-3 and a 33-kDa protein having LDH activity was synthesized in Escherichia coli. P. falciparum LDH primary structure displays high amino acid similarity (50-57%) to vertebrate and bacterial LDH, but lacks the amino terminal extension observed in all vertebrate LDH. The majority of amino acid residues implicated in substrate and coenzyme binding and catalysis of other LDH are well conserved in P. falciparum LDH. However, several notable differences in amino acid composition were observed. P. falciparum LDH contained several distinctive single amino acid insertions and deletions compared to other LDH enzymes, and most remarkably, it contained a novel insertion of 5 amino acids within the conserved mobile loop region near arginine residue 109, a residue which is known to make contact with pyruvate in the ternary complex of other LDH. These results suggest that novel features of P. falciparum LDH primary structure may be correlated with previously characterized and distinctive kinetic, biochemical, immunochemical, and electrophoretic properties of P. falciparum LDH. PMID- 8515778 TI - Amino acid sequence of the NH2-terminus of Plasmodium knowlesi lactate dehydrogenase. PMID- 8515779 TI - Members of the SAPA/trans-sialidase protein family have identical N-terminal sequences and a putative signal peptide. PMID- 8515780 TI - Sequence of a 27-kilodalton gamete antigen of Plasmodium reichenowi and comparison with Pfg27 of Plasmodium falciparum. PMID- 8515781 TI - Molecular karyotype of related clones of Entamoeba histolytica. AB - The molecular karyotype of 3 clones derived from strain HM1:IMSS of Entamoeba histolytica was studied by transverse alternating field electrophoresis. 11-20 bands ranging between 0.3 and over 3 Mb were resolved. Hybridization with total DNA detected highly repetitive sequences in the slow-migrating molecules, while non-repetitive sequences were located in the intermediate and fast-migrating molecules. rDNA, tubulin, actin, cysteine proteases DNA fragments, and a variable DNA sequence (EhVR1) located the respective genes mainly in the 1.3-1.5-Mb region, although they differed in the three clones. Two-dimensional transverse alternating field electrophoresis showed that more than one high-molecular weight molecule may comigrate in a single DNA band. rDNA, and EhVR1 hybridized with slow migrating bands in a characteristic ladder pattern. Most of the bands recognized by EhVR1 seems to be linear molecules, although exonuclease III-resistant bands also hybridized with EhVR1, suggesting the presence of circles. PMID- 8515782 TI - Small subunit ribosomal RNA+ of Hexamita inflata and the quest for the first branch in the eukaryotic tree. AB - A phylogenetic analysis of the small subunit ribosomal RNA (16S-like rRNA) coding region from Hexamita inflata demonstrates that parasitism alone cannot explain early diverging eukaryotic lineages. Parasitic and free-living diplomonads, as well as trichomonads and microsporidia, diverge at the base of the eukaryotic tree. The relative branching order of diplomonads, trichomonads and microsporidia is influenced by outlying prokaryotic taxa with different G+C compositions in their rRNA coding regions. The high G+C prokaryotes position Giardia lamblia at the base of the eukaryotic tree but split diplomonads into a paraphyletic group. When the outlying groups are restricted to rRNAs with nominal G+C compositions, diplomonads form a monophyletic group that diverged after the microsporidia and trichomonads. This unstable branching pattern correlates with unusual nucleotide compositions in the rRNAs of G. lamblia (75% G+C) and Vairimorpha necatrix (35% G+C). In contrast, the 51% G+C composition of the H. inflata rRNA is typical of other eukaryotic rRNAs. Its divergence after trichomonads is strongly supported by bootstrap replicates in distance analyses that do not include G. lamblia. Because of a low G+C composition in its rRNA coding region, the phylogenetic placement of V. necatrix is uncertain and the identity of the deepest branching eukaryotic lineage is ambiguous. PMID- 8515783 TI - A family of transcripts (K2) of Entamoeba histolytica contains polymorphic repetitive regions with highly conserved elements. AB - Sera from patients with invasive amebiasis were used to identify a cDNA clone (K2p-1) encoding a commonly recognized, repeat-containing antigen of the pathogenic Entamoeba histolytica HM-1:IMSS. K2p-1 was used to isolate 3 cDNA clones (K2 clones); one K2p-1 related clone from the same pathogenic E. histolytica strain and 2 from the nonpathogenic E. histolytica strain SAW-142. The nucleotide sequence and predicted amino acid sequence revealed a closely related family of transcripts differing mainly in the extent and arrangement of an internal region consisting of tandemly arranged repetitive elements. The repetitive units encoding either 12 or 8 amino acids were found to be highly conserved in all the K2 clones analyzed so far, suggesting that the repeat motifs perform functions common to both pathogenic and nonpathogenic E. histolytica. The genomic organization of the K2 genes was different when compared in pathogenic and nonpathogenic E. histolytica and may therefore be used to discriminate between pathogenic and nonpathogenic E. histolytica strains. PMID- 8515785 TI - Two major phosphoproteins of Plasmodium falciparum are heat shock proteins. AB - Two major phosphoproteins of Plasmodium falciparum could be identified by partial amino acid sequencing as the plasmodial members of the hsp 70 heat shock protein family, Pfhsp and Pfgrp. According to phosphoamino acid analyses of Pfhsp and Pfgrp isolated from [32P]orthophosphate-labeled malarial cultures, both proteins were phosphorylated in Ser and Thr. While Pfhsp contains higher amounts of labeled phosphoserine, Pfgrp contains higher amounts of phosphothreonine. Phosphorylation of both proteins increased throughout the entire erythrocytic growth cycle. At the trophozoite and schizont stages Pfhsp and Pfgrp are the most prominent phosphoproteins of Plasmodium falciparum. Using multiply redundant oligonucleotides directed against the N-terminus of Pfgrp we cloned and sequenced the entire Pfgrp gene. The gene encodes a product with a predicted length of 652 amino acids. The deduced amino acid sequence has identities of 65.5% and 65.0% to the human and rat grp78 proteins, respectively. Pfgrp possesses a classical N terminal leader sequence. The published grp78 related gene sequences of Plasmodium falciparum are all fragments of the same plasmodial gene. PMID- 8515784 TI - Cloning and characterization of a Plasmodium falciparum gene encoding a novel high-molecular weight host membrane-associated protein, PfEMP3. AB - The rat monoclonal antibody, mAb 12C11, reacts with numerous proteins from mature asexual stages of Plasmodium falciparum. The largest is 315 kDa and is designated PfEMP3. A lambda gt11 expression library, generated from genomic DNA of Malayan Camp strain parasites, was screened with mAb 12C11. One positive clone, lambda 12.1.3, contained a 1.4-kb fragment in frame with the beta-galactosidase gene of lambda gt11. The deduced 455-amino acid sequence is a novel, highly charged sequence encoding two 15-amino acid repeats at the N-terminus followed by 27 repeats of 13 amino acids. The last 59 C-terminal residues are non-repetitive. Two in-frame stop codons at the 3' end of the DNA suggests that this DNA fragment encodes the C-terminus of the protein. Southern blotting with the cloned fragment identified two copies of this fragment per haploid genome in knob-positive, parasitized erythrocytes (K+PE). Both DNA fragments are absent from K - PE. Northern blotting of trophozoite-stage PE total RNA revealed mRNAs of 10, 4.4 and 2 kb in K+PE, but no hybridization with K - PE. Immune sera were elicited against the lambda 12.1.3 beta-galactosidase fusion protein and peptides generated from the predicted lambda 12.1.3 amino acid sequence. These sera and mAb 12C11 reacted specifically with PfEMP3 in Western blots of mature K+PE but not with K - PE. Rat and mouse sera against the recombinant protein produced an immunofluorescence pattern in fixed mature K+PE almost identical to the pattern produced by a monoclonal antibody against the knob-associated protein, Histidine Rich Protein 1. The same antibodies were immunofluorescence negative with fixed K - PE. Mouse antibodies against the recombinant protein reacted on immunoelectron microscopy with the erythrocyte membrane of K+PE, labeling knobs as well as the membrane between knobs. In contrast, a mAb against Histidine Rich Protein 1 reacted only under the electron dense material of knobs. We conclude that the lambda 12.1.3 clone encodes the C-terminal portion of the 315 kD PfEMP3 antigen and that PfEMP3 may be involved in knob formation or other perturbations of the erythrocyte membrane. PMID- 8515786 TI - Sequence conservation in the C-terminal part of the precursor to the major merozoite surface proteins (MSP1) of Plasmodium falciparum from field isolates. AB - The C-terminal part of the precursor to the major merozoite surface proteins (MSP1) of Plasmodium falciparum contains potential protective epitopes and two cleavage sites for processing which take place prior to erythrocyte invasion by the merozoite. Since sequences available to date are limited and derived from cultured parasites, we have examined the extent of variations of this important part of the MSP1 gene from natural populations. Our sequence analyses of 1.6-1.7 kb from blocks 13-17 of the gene obtained from 19 Thai wild isolates have identified a deletion of a codon and 18 nucleotide substitutions, all of which are dimorphic substitutions and all but one create amino acid exchanges. However, residues at two cleavage sites for the C-terminus 42 kDa polypeptide and the 19 kDa polypeptide, a subfragment of the former, are conserved. Furthermore, all 12 cysteine residues at the C-terminal 19-kDa polypeptide are perfectly conserved, allowing the formation of 2 epidermal growth factor-like structures. These results indicate that in contrast to extensive variations at the N-terminal part of MSP1, limited variations occur at the C-terminal part. PMID- 8515787 TI - Effects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group. AB - BACKGROUND: Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. METHODS: Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. Afer 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients). RESULTS: Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 percent of the patients. CONCLUSIONS: Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown. PMID- 8515788 TI - Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. AB - BACKGROUND: Clozapine is an atypical antipsychotic agent that is more effective than standard neuroleptic drugs in the treatment of patients with refractory schizophrenia. Unlike classic neuroleptic agents, clozapine is not associated with the development of acute extrapyramidal symptoms or tardive dyskinesia. The main factor limiting its use is the risk of potentially fatal agranulocytosis, estimated to occur in 1 to 2 percent of treated patients. After clozapine was approved by the Food and Drug Administration, it became available for marketing in the United States in February 1990 only as part of a special surveillance system (the Clozaril Patient Management System, or CPMS), in which a weekly white cell count was required for the patient to receive a supply of the drug. METHODS: We evaluated the CPMS data for February 1990 through April 1991 by survival analysis to determine the incidence of agranulocytosis and the effects of potential risk factors such as age and sex. Data were available for 11,555 patients who received clozapine during the period after marketing began. RESULTS: Agranulocytosis developed in 73 patients, resulting in death from infectious complications in 2 patients. Episodes of agranulocytosis occurred in 61 patients within three months after they began treatment. The cumulative incidence of this side effect was 0.80 percent (95 percent confidence interval, 0.61 to 0.99) at 1 year and 0.91 percent (95 percent confidence interval, 0.62 to 1.20) at 1 1/2 years. The risk of agranulocytosis increased with age and was higher among women. CONCLUSIONS: The occurrence of agranulocytosis is a substantial hazard of the administration of clozapine, but this hazard can be reduced by monitoring the white-cell count. The increasing risk of agranulocytosis with age and the reduced incidence after the first six months of treatment provide additional guidelines for the prescription and monitoring of clozapine treatment in the future. PMID- 8515789 TI - Brief report: a single neoplastic clone in sequential biopsy specimens from a patient with primary gastric-mucosa-associated lymphoid-tissue lymphoma and Sjogren's syndrome. PMID- 8515790 TI - Acute promyelocytic leukemia. AB - Perhaps the most important advance in this field is not the specific actions of all-trans-retinoic acid in acute promyelocytic leukemia, but rather the conclusive documentation of differentiation as a practical and consistently effective method of treating human cancer. As a drug, all-trans-retinoic acid has certain undesirable pharmacologic properties that might be overcome by the use of alternative retinoids, such as 9-cis-retinoic acid, that are equally active against acute promyelocytic leukemia cells in vitro. In addition to retinoids that selectively activate RARs or RXRs, other ligands of the steroid-thyroid receptor superfamily, such as vitamin D3, glucocorticoids, and sex steroids also have cytodifferentiating actions in model systems. Numerous other agents can effect differentiation of neoplastic cells in such systems, including sodium butyrate, hexamethylene bisacetamide and its analogues, colony-stimulating factors, and interferons. Each of these compounds apparently acts through different pathways, and their activity may be greatly amplified when they are used in combination. Just as the practical usefulness of all-trans-retinoic acid in combination with conventional treatments continues to evolve, the use of differentiation agents in combination represents a novel and promising approach for oncologic therapy in the next decade. Although acute promyelocytic leukemia remains an "orphan" disease, its importance as a model for human neoplasia should not be minimized. The specific molecular lesion of acute promyelocytic leukemia is not shared by other cancers, but the physiologic actions of retinoids, their documented cytodifferentiating activity against a variety of human cancer cells in vitro, and their usefulness in cancer chemoprevention are clearly not mediated by identifiable mutations of retinoid receptors. The insights into transformation and leukemogenesis gained in acute promyelocytic leukemia may be a harbinger of further clinical applications and offer a glimpse into the next generation of cancer therapy. PMID- 8515791 TI - Iron deficiency in infancy and childhood. PMID- 8515792 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 28-1993. A 63-year-old man with fever, sweats, and shaking chills. PMID- 8515793 TI - The search for the ideal positive inotropic agent. PMID- 8515794 TI - Clozapine--deciphering the risks. PMID- 8515795 TI - Inhaled nitric oxide for the adult respiratory distress syndrome. PMID- 8515796 TI - Endoscopic laser third ventriculostomy. PMID- 8515797 TI - Gynecomastia. PMID- 8515798 TI - Laboratory-acquired Gambian trypanosomiasis. PMID- 8515799 TI - Hypokalemic myopathy induced by Giardia lamblia. PMID- 8515800 TI - Medicaid coverage of oral rehydration solutions. PMID- 8515801 TI - Pandemonium in the modern hospital. PMID- 8515802 TI - Auto PEEP. PMID- 8515803 TI - Duesberg's anti-AZT campaign continues. PMID- 8515804 TI - British group backs French scientist. PMID- 8515805 TI - Doctors' dilemma paralyses French medicine. PMID- 8515806 TI - NIH appointment due. PMID- 8515807 TI - Transcription. Efficiency in activation. PMID- 8515808 TI - Enzymes. Snapshots along the pathway. PMID- 8515809 TI - Antifreeze protein in snake venom? PMID- 8515810 TI - Type 5 adenylyl cyclase distribution. PMID- 8515811 TI - Health risks and natural gas. PMID- 8515812 TI - Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase. AB - Crystal structures of haloalkane dehalogenase were determined in the presence of the substrate 1,2-dichloroethane. At pH 5 and 4 degrees C, substrate is bound in the active site without being converted; warming to room temperature causes the substrate's carbon-chlorine bond to be broken, producing a chloride ion with concomitant alkylation of the active-site residue Asp124. At pH 6 and room temperature the alkylated enzyme is hydrolysed by a water molecule activated by the His289-Asp260 pair in the active site. These results show that catalysis by the dehalogenase proceeds by a two-step mechanism involving an ester intermediate covalently bound at Asp124. PMID- 8515813 TI - Numerous candidate plasticity-related genes revealed by differential cDNA cloning. AB - Plasticity is a property of the nervous system that allows it to modify its response to an altered input. This capacity for change suggests that there are molecular mechanisms in neurons that can couple stimuli to long-term alterations in phenotype. Neuronal excitation elicits rapid transcriptional activation of several immediate-early genes, for example c-fos, c-jun and zif268. Many immediate-early genes encode transcription factors that control expression of downstream genes whose products are believed to bring about long-term plastic changes. Here we use a highly sensitive differential complementary DNA cloning procedure to identify genes that may participate in long-term plasticity. We cloned 52 cDNAs of genes induced by the glutamate analogue kainate in the hippocampus dentate gyrus. The number of these candidate plasticity-related genes (CPGs) is estimated to be 500-1,000. One of the cloned CPGs (16C8), encoding a protease inhibitor, is induced by a stimulus producing long-term potentiation and during dentate gyrus development; a second, cpg1, is dependent on activation of the NMDA (N-methyl-D-aspartate) receptor for induction and encodes a new small, dentate-gyrus-specific protein. Seventeen of the cloned CPGs encode known proteins, including six suggesting that strong neuronal activation leads to de novo synthesis of vesicular and other synaptic components. PMID- 8515814 TI - Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. AB - The fragile X syndrome is the most frequent form of inherited mental retardation after Down's syndrome, having an incidence of one in 1,250 males. The fragile X syndrome results from amplification of the CGG repeat found in the FMR-1 gene. This CGG repeat shows length variation in normal individuals and is increased significantly in both carriers and patients; it is located 250 base pairs distal to a CpG island which is hypermethylated in fragile X patients. The methylation probably results in downregulation of FMR-1 gene expression. No information can be deduced about the function of the FMR-1 protein from its predicted sequence. Here we investigate the nature and function of the protein encoded by the FMR-1 gene using polyclonal antibodies raised against the predicted amino-acid sequences. Four different protein products, possibly resulting from alternative splicing, have been identified by immunoblotting in lymphoblastoid cell lines of healthy individuals. All these proteins were missing in cell lines from patients not expressing FMR-1 messenger RNA. The intracellular localization of the FMR-1 gene products was investigated by transient expression in COS-1 cells and found to be cytoplasmic. Localization was also predominantly cytoplasmic in the epithelium of the oesophagus, but in some cells was obviously nuclear. PMID- 8515815 TI - Peptide binding inhibits protein aggregation of invariant-chain free class II dimers and promotes surface expression of occupied molecules. AB - Efficient egress of major histocompatibility complex (MHC) class I molecules from the endoplasmic reticulum (ER) depends on peptide binding. For MHC class II molecules, invariant chain (Ii) promotes ER exit of newly assembled, peptide-free dimers. This raises the question of whether a mechanism exists elsewhere in the cell that dictates selective expression of peptide-associated class II molecules. We report here that dissociation of MHC class II-Ii complexes at low pH and physiological temperature leads to inclusion of empty class II in protein aggregates, and that this aggregation is specifically prevented by peptide binding. Combined with data showing that antigen exposure increases cell surface class II expression on living cells by a post-translational mechanism, these results provide evidence for peptide-dependent intracellular editing of class II dimers, which limits surface expression of empty molecules unsuitable for antigen specific T-cell activation. PMID- 8515816 TI - The SCID-hu mouse as a model for HIV-1 infection. AB - During normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1 infected adults and children, and in some fetuses aborted from infected women. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect. The model is constructed by implanting human fetal liver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology. PMID- 8515817 TI - Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase. AB - The G2-M phase transition in eukaryotes is regulated by the synergistic and opposing activities of a cascade of distinct protein kinases and phosphatases. This cascade converges on Cdc2, a serine/threonine protein kinase required for entry into mitosis (reviewed in ref. 1). In the fission yeast Schizosaccharomyces pombe, inactivation of the Cdc2/cyclin B complex is achieved by phosphorylation of tyrosine 15 by Wee1 (refs 2,3). The action of the Wee1 kinase is opposed by the action of the Cdc25 phosphatase, which dephosphorylates Cdc2 on tyrosine 15, thereby activating the Cdc2/cyclin B complex. Much less is known about the regulatory signals upstream of cdc25 and wee1. Genetics indicate that the mitotic inducer nim1/cdr1 acts upstream of wee1, possibly as a negative regulator of wee1 (refs 10, 11). To characterize the nim1/cdr1 protein (Nim1), we have overproduced it in both bacterial and baculoviral expression systems. We report that Nim1 possesses intrinsic serine-kinase, threonine-kinase and tyrosine-kinase activities. Co-expression of the Nim1 and Wee1 kinases in insect cells results in the phosphorylation of Wee1 and therefore a shift in its electrophoretic mobility on SDS-polyacrylamide gels. When Wee1 is phosphorylated, its ability to phosphorylate Cdc2 on tyrosine 15 is inhibited; treatment with phosphatase restores this kinase activity. Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro. These results show that nim1/cdr1 functions as a positive regulator of mitosis by directly phosphorylating and inactivating the mitotic inhibitor Wee1. PMID- 8515818 TI - Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase. AB - In most species, including the fission yeast Schizosaccharomyces pombe, the Cdc2/cyclin B mitosis-inducing kinase is maintained in an inhibited state during interphase as a result of phosphorylation of a tyrosine residue in the ATP binding region of Cdc2 (refs 1-3). This site is phosphorylated by Wee1 kinase and dephosphorylated by Cdc25 phosphatase. In fission yeast an additional element of the G2/M control Nim1/Cdr1 kinase, has been identified which functions as a potent mitotic inducer. These studies suggested that Nim1 acts by inhibiting Wee1, perhaps by direct phosphorylation. Consistent with this model, we report here that Wee1 is hyperphosphorylated in cells that overproduce Nim1. Likewise, Wee1 phosphorylation is reduced in nim1- cells. Highly purified Nim1 kinase phosphorylates Wee1 in vitro, resulting in strong inhibition of Wee1 kinase. These observations show that Nim1 promotes the onset of mitosis by inhibiting Wee1. PMID- 8515819 TI - Interaction between an acidic activator and transcription factor TFIIB is required for transcriptional activation. AB - How eukaryotic promoter-specific activator proteins (activators) stimulate transcription is a central question. We have previously shown that an acidic activator can directly interact with the general transcription factor TFIIB and increase its stable assembly into a preinitiation complex. We have proposed that this increase in TFIIB assembly is at least part of the mechanism by which an acidic activator functions. A prediction of this hypothesis is that a TFIIB mutant unable to interact with an acidic activator could not support activated transcription, and here we present experiments that verify this prediction. In conjunction with previous studies, our results argue that interaction between an acidic activator and TFIIB is necessary for transcriptional activation. PMID- 8515820 TI - Functional dissection of TFIIB domains required for TFIIB-TFIID-promoter complex formation and basal transcription activity. AB - The protein TFIIB is a general transcription initiation factor that interacts with a promoter complex (D.DNA) containing the TATA-binding subunit (TFIID tau, or TBP) of TFIID to facilitate subsequent interaction with RNA polymerase II (ref. 2) through the associated TFIIF (ref. 3). The potential bridging function of TFIIB raises the possibility of two structural domains and emphasizes the importance of TFIIB structure-function studies for a further understanding of preinitiation complex assembly and function. Here we show that human TFIIB (refs 5,6) is comprised of functionally distinct N- and C-terminal domains. The C terminal domain, containing the direct repeats and associated basic regions, is necessary and sufficient for interaction with the D.DNA complex. By contrast, the N-terminal domain that is dispensable for formation of the TFIID tau-TFIIB promoter (D.B.DNA) complex is required for subsequent events leading to basal transcription initiation. On the basis of these results, we discuss structural and functional similarities between TFIIB and TFIID tau, which have similar structural organization and motifs. PMID- 8515821 TI - Anxiety in the Lundby Study: re-evaluation according to DSM-III-R, incidence and risk. AB - This study presents the incidence and risk of Anxiety Disorders according to DSM III-R in the 1947 Lundby cohort. The figures are based on a re-evaluation of 124 first-ever episodes of 'Anxiety' according to the Lundby definition. Panic Disorders without/with Agoraphobia constituted the largest groups, while a proportionally low rate of Generalized Anxiety Disorder was obtained. The incidence rates per 100 person years in Panic Disorders without Agoraphobia were 0.07 for men and 0.20 for women, the female dominance being statistically significant. Corresponding figures in Panic Disorders with Agoraphobia were 0.04 and 0.07. About 20% fell into other diagnostic categories, the most dominating being Mood and Adjustment Disorders and Hypochondriasis. Comparisons with incidence rates from the ECA and Stirling County studies are made and outlines for further research presented. PMID- 8515822 TI - Effect of scopolamine on spontaneous yawning in men. AB - The effect of scopolamine hydrobromide (0.4 mg s.c.) on spontaneous yawning was studied in 16 male volunteers in a double-blind study. Scopolamine (or placebo) was given 60 min before (-60 min) placebo (physiological saline s.c.) (time 0 min) and yawning monitored from -15 to +60 min by recording displacement of the lower jaw and storing the traces on diskettes. After placebo, the number of yawns was 5.3 +/- 1.4 (means +/- SE) and after scopolamine pretreatment 4.3 +/- 1.6 (p = NS). Drowsiness was assessed with the Stanford Sleepiness Scale and the Analog Sleepiness Scale at -15, 0, +20, +40, +60 min. There was no significant correlation between total sleepiness scores (area under the curve, 0 min to +60 min), peak sleepiness score or peak increment in sleepiness score and number of yawns on either scale. These data suggest that (a) spontaneous yawning in man is not mediated by a central muscarinic cholinergic link, and (b) the assumed relationship between drowsiness and yawning remains to be verified experimentally. PMID- 8515823 TI - EEG profile of three different extractions of Ginkgo biloba. AB - Two experiment were conducted to assess the electroencephalographic effects of (1) three different dosages of a total extract of Ginkgo biloba (EGb 761, Tebonin) and (2) three different extractions of G. biloba (Tebonin and two fractions from it). The medicament was tested against placebo using a double blind cross-over design in 12 normal healthy males for each experiment. Medication was administered for 3 days preceding the recording sessions. 25 parameters were computed from the EEG spectra. Medication-related effects were obtained for most of the power measures, whereas dominant frequencies of the respective frequency band remained largely unchanged. The differences between the EEG effects of the two studies are critically discussed. PMID- 8515824 TI - Effects of oxazepam and an extract of kava roots (Piper methysticum) on event related potentials in a word recognition task. AB - Twelve healthy volunteers were tested in a double-blind crossover study to assess the effects of oxazepam and an extract of kava roots (Piper methysticum) on behavior and event-related potentials (ERPs) in a recognition memory task. The subjects' task was to identify within a list of visually presented words those that were shown for the first time and those that were being repeated. The repeated words were associated with an increased positivity beginning approximately 250 ms poststimulus. Oxazepam led to a reduction of a negative component in the 250-500 ms range for both old and new words and to a reduction of the old/new difference in the ERP associated with a significantly worse recognition rate. Kava on the other hand showed a slightly increased recognition rate and a larger ERP difference between old and new words. PMID- 8515825 TI - Amplitudes of auditory P300 in remitted and residual schizophrenics: correlations with clinical features. AB - The parameters of auditory P300 were studied with reference-independent methods in a group of 18 remitted and residual schizophrenics, and in 18 age- and sex matched controls. In the schizophrenic group, significant inverse correlations were found between P300 amplitudes and level of psychopathology assessed with the Scale for Assessment of Negative Symptoms and with the Brief Psychiatric Rating Scale. Clinical variables regarding social functioning and adaptation, assessed with the Schedule for Affective Disorders and Schizophrenia, and with axis V of DSM-III-R, correlated significantly with low amplitudes. The scalp locations of the maxima and minima of the P300 potentials had the tendency to be dislocated to the right in schizophrenics compared with controls. The results indicate low P300 amplitudes to be associated with pervasive cognitive impairment. Future studies will determine whether low P300 amplitudes have prognostic validity for course and outcome of schizophrenic disorders. PMID- 8515826 TI - The hematopoietic system influences odor specificity in mice and rats. AB - The change in strain-specific urine odors which appears after bone marrow transplantations was examined in mice and rats in order to demonstrate an influence of the hematopoietic system on urinary chemosignals. Four rats were trained in an olfactometer to discriminate two allogeneic mouse or rat strains via their urine odors. Urine samples obtained from two inbred strains of mice, from two inbred strains of rats, from allogeneic reconstituted mice, and from semiallogeneic reconstituted rats were combined in a number of 'transfer of training' tests. Results confirm findings that the hematopoietic system influences odor specificity in mice. For the first time a change of urinary chemosignals after bone marrow transplantation in rats was demonstrated by using semiallogeneic reconstituted rat chimeras. PMID- 8515827 TI - Restriction to a limited set of EEG-target variables may lead to misinterpretation of pharmaco-EEG results. AB - The number and types of target variables quantified from the spectrally analyzed EEG used in topographic pharmaco-EEG studies are still being discussed. Drug induced changes of target variables obtained in the alpha frequency band--four absolute and four relative powers as well as three frequency measures--were utilized to assess the effects of xantinolnicotinate in demented patients using a parallel group design and the effects of buspirone in a double-blind, placebo controlled crossover design. We conclude that for the proper evaluation of the different drug effects on the alpha activity, all these target variables should be considered. Descriptive p values of multiple comparisons within the framework of descriptive data analyses are important tools in interpreting drug effects. PMID- 8515828 TI - Structural brain abnormalities in catatonia. AB - In this study, the ventricle to brain ratios of catatonic subjects were compared and evaluated with respect to the underlying diagnoses. Catatonic individuals with the diagnosis of schizophrenia were more likely to have greater ventricle to brain ratios than other catatonic subjects. The association of large ventricles with chronic, deteriorating psychosis is maintained and the heterogeneity of the syndrome of catatonia is apparent. It is possible that the presence of large ventricles may be useful to predict the chronicity of disability for some cases of catatonia. PMID- 8515829 TI - Noradrenergic and hormonal responses to physical exercise in adolescents. Relationship to anxiety and tolerance to frustration. AB - Seventy physically healthy 14-year-old adolescents, 40 boys and 30 girls, were evaluated psychologically and endocrinologically. After the psychological tests (Anxiety Score Test for Adolescents, Rosenzweig, Pictures Frustration Test for Children), subjects were divided into group A, with low anxiety/sense of guilt and high self-esteem/tolerance to frustration and group B with the opposite. In both groups, we measured basal plasma levels of noradrenaline (NE), growth hormone (GH), prolactin (PRL), melatonin (MT) and luteinizing hormone (LH) and their response to physical exercise (the Harvard step test). Basal levels of the hormones and of NE were not different in the two groups. After the physical stimulus, NE levels rose significantly more in B girls than in A and significantly less in B than in A boys. GH and PRL levels increased only in A girls and MT in B boys, while LH levels decreased in A boys and girls but not in B subjects. PMID- 8515830 TI - Premorbid personality traits and psychosomatic background factors in depression: the Lundby Study 1957-1972. AB - The search for specific predepressive personality factors has a long tradition in psychiatry. Studies in which assessments were made prospectively, before the onset of a first-ever episode of the illness, are, however, rare. In the present report from the Lundby Study we have investigated premorbid, mainly personality related background factors for first incidences of depressive disorder, diagnosed according to the Lundby criteria for 'Depression proper' and 'Depression plus other psychiatric symptoms'. The items found to be of a predictive value differed between the two diagnostic subgroups and also between men and women. The findings are discussed and compared with earlier predictor studies on depression. PMID- 8515831 TI - A few electroconvulsive shocks produce more reliable effects of firing rate in lateral septal neurons than repetitive treatment in the rat. AB - Electroconvulsive shock is a common treatment used in depression, especially in cases in which suicide constitutes a risk. The recommendation for its use varies from one place to another, but there is an empirical agreement to avoid daily treatment or several treatments on the same day. The present study explored the actions of electroconvulsive shock in lateral septal firing rate in rats. The first or second once-a-day electroconvulsive shock produced a maximal increase in firing rate; however, effects vanished as treatment was repeated. Three consecutive electroconvulsive shocks on the same day also produced fewer changes in firing rate than once-a-day treatment. These results are likely to be related to clinical recommendations to avoid serial-repetitive treatment, and suggest that some resting time is required in treatment to achieve long-lasting changes in neuronal activity. PMID- 8515832 TI - Sleep deprivation is a less potent agent than clomipramine in increasing firing rate in lateral septal neurons in the rat. AB - Acute injection of clomipramine or a 24-hour period of sleep deprivation produces an increased firing rate in lateral septal neurons of the rat. However, it is unknown whether changes in firing rate in lateral septal neurons also appear after repetitive treatments. This study explored and compared the effects of long term clomipramine with those of sleep deprivation from 1 to 4 days in the firing rate of lateral septal neurons. The firing rate increased after both treatments; however, maximal effects occurred on different days. Clomipramine (1.25 mg/kg, i.p., twice a day) produced a stable, increased firing rate after 20 days of treatment. Twenty-four hours of total sleep deprivation produced changes in firing rate comparable to 10 days of clomipramine treatment. Changes in firing rate did not appear when animals were exposed to 12 h of sleep deprivation alternated with 12 h in housing cages. Therefore, it is concluded that 24 h of total sleep deprivation is a less effective treatment than clomipramine for producing changes in firing rate in lateral septal neurons. PMID- 8515833 TI - Clomipramine enhances the excitatory actions of dorsal raphe nucleus stimulation in lateral septal neurons in the rat. AB - Clomipramine is a serotonin reuptake blocker which produces an increased rate of firing in lateral septal neurons of the rat. However, it is unknown whether the response of dorsal raphe nucleus stimulation on the firing rate of the lateral septal neurons is modified by clomipramine treatment. Two programs of stimulation were employed. In the first, iterative stimulation (0.3 Hz, 1 ms, 0.1 mA) produced a complex pattern of response in which activation responses predominated, and clomipramine increased the duration and the firing rate of afterdischarge. In the second program a short train of pulses (300 Hz, 500 ms, 0.1 ms) was applied to the dorsal raphe nucleus. Clomipramine increased both the duration and the frequency of firing with respect to the saline-treated group. The present data show that dorsal raphe nucleus stimulation produces a long lasting increase in the firing rate of lateral septal neurons which is enhanced by clomipramine. Since clomipramine applied to the septal area produces a decrease in firing, it is concluded that actions taken by clomipramine on raphe nuclei produce a disinhibitory process in the lateral septal neurons. PMID- 8515834 TI - Gonadal hormone correlates of sensation seeking and anxiety in healthy human females. AB - The present study focused on exploring the relationship between a number of personality measures (Sensation Seeking Scale, SSS; State-Trait Anxiety Inventory, STAI; and Susceptibility to Punishment Scale, SP) and some parameters of the pituitary-gonadal axis (FSH, LH and 17 beta-estradiol). The study was carried out with a group of 37 female volunteers. The subjects were physically and mentally fit. None of them had a personal history of psychiatric or endocrine illness. All subjects were studied at the beginning of the follicular phase. The most relevant results showed an 'inverted U shape' relationship between sensation seeking and plasma FSH levels. Lower Thrill and Adventure Seeking (TAS) scores were also found in subjects with higher levels of 17 beta-estradiol. PMID- 8515835 TI - Sex hormone-related variations of cognitive performance in !Kung San hunter gatherers of Namibia. AB - The relation of circulating sex hormones and cognitive abilities was investigated in 114 healthy !Kung San men ('bushmen') of Namibia/Southern Africa who lived mainly as traditional hunter-gatherers. Blood and saliva samples were analysed by use of radioimmunoassays in order to determine the serum concentrations of total testosterone (Tser), 5 alpha-dihydrotestosterone (DHT), and estradiol (E2), as well as the level of bioavailable, non-SHBG-bound 'free' testosterone in the saliva. The cognitive ability was assessed with two verbal (verbal fluency) and three nonverbal tests (tactual-spatial functioning, field independence/field dependence). As to be expected from previous research on Western samples, all three androgens but not E2 are of significance to the !Kung San men's cognitive performance. Tser exhibits a positive relation to tactual-spatial abilities and to the degree of lateralization of this task; on the other hand, Tser is negatively correlated with verbal fluency. Testosterone in the saliva is also significantly positively correlated to tactual-spatial test scores and, in addition, to field independence. DHT and the ratio DHT/Tser are positively related to verbal fluency and negatively to the degree of lateralization of tactual-spatial performance. PMID- 8515836 TI - Secretoneurin releases dopamine from rat striatal slices: a biological effect of a peptide derived from secretogranin II (chromogranin C). AB - Proteolytic processing of secretogranin II (chromogranin C) in brain leads to the formation of a 33-amino acid peptide which we have named secretoneurin. All the properties of secretoneurin are consistent with the concept that this peptide represents a neuropeptide. However, a biological function has not yet been demonstrated. Therefore, we have now investigated whether secretoneurin could alter transmitter release in brain. Slices of rat caudate-putamen were superfused in an in vitro system and dopamine was measured in the superfusate. Secretoneurin dose-dependently increased the outflow of dopamine. This response was abolished in Ca(2+)-free medium. The secretoneurin-response could also be blocked by preincubation of the peptide with a specific antiserum and was subject to rapid specific and reversible desensitization. This effect on dopamine release constitutes the first discovered biological effect found for a peptide derived from secretogranin II. Thus, secretoneurin can be added to the ever-growing number of neuropeptides. PMID- 8515837 TI - Low-affinity p75 nerve growth factor receptor expression in the embryonic monkey telencephalon: timing and localization in diverse cellular elements. AB - Monoclonal antibodies against the low-affinity (p75) subunit of the human nerve growth factor receptor have been used to determine the temporal appearance of this receptor and to identify the associated cellular elements in the developing occipital cortex of rhesus monkeys. Adult and fetal brains from embryos at embryonic days 45-121 were used. This embryonic time span includes periods of active neurogenesis, cell migration and initial formation of axonal connections in the cerebral cortex. The first immunolabeling in the developing cerebral wall was seen between embryonic days 56 and 64. The labeling was present in the transient subplate neurons, a small number of axonal processes and pericytes associated with blood vessels. By birth, labeled neurons of the subplate zone disappeared, but immunolabeled axonal processes could now be seen in large numbers in the cortex. These findings are consistent with the role of nerve growth factor in the coordination of cortical differentiation, but not with the initiation of neuronal proliferation, since the emergence of nerve growth factor receptor-labeled elements in the cortex occurs two to three weeks after the onset of neurogenesis in this species. Further, the diverse cellular elements labeled in the fetal cerebrum with the antibodies to the low-affinity nerve growth factor receptor suggests that a receptor or receptors associated with growth factor signaling for more than one growth factor family are recognized by these antibodies. Differential timing in the expression of families of growth factor receptors may be one mechanism by which developing neurons in the cerebral cortex could respond to the different signals which guide such processes as synaptogenesis and morphogenesis. PMID- 8515838 TI - Widespread increases in regional hypothalamic neuropeptide Y levels in acute cold exposed rats. AB - Neuropeptide Y injected into the hypothalamus or third ventricle stimulates feeding and inhibits the sympathetic activation of brown adipose tissue. To clarify the involvement of hypothalamic neuropeptide Y in cold-induced thermogenesis, groups of rats exposed to 4 degrees for 2.5 or 18 h were compared with warm-adapted rats (22 degrees C). Neuropeptide Y was measured in eight selected hypothalamic regions, including those known to be involved in the regulation of energy expenditure. Activation of brown adipose tissue was confirmed by significant six- to nine-fold increases in brown adipose tissue uncoupling protein messenger RNA. Compared with warm-adapted controls, neuropeptide Y levels were significantly raised by 80-170% in several hypothalamic regions of rats exposed to cold for 2.5 h, namely the medial preoptic area, paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamic area. Neuropeptide Y levels in 18-h cold-exposed rats were similarly elevated in these regions and were also significantly increased in the anterior hypothalamic area (75%). By contrast, neuropeptide Y levels in the arcuate nucleus, the main hypothalamic site of synthesis, were not increased by cold exposure, being significantly reduced by 21% after 2.5 h exposure and comparable with controls after 18 h. As neuropeptide Y injection inhibits brown adipose tissue activation, we suggest that the rapid and dramatic increases in neuropeptide Y levels in specific hypothalamic regions occur because cold exposure might inhibit the release of neuropeptide Y and so cause accumulation of neuropeptide Y in these sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8515839 TI - Immunohistochemical localization of GABA in the mammillary complex of the rat. AB - The distribution and synaptic organization of GABAergic elements in the mammillary nuclei of rats have been examined by the immunocytochemical localization of GABA at the light and electron microscope levels. The distribution of GABA-immunoreactive fibres and terminals in the mammillary body is non-homogeneous. By light microscopy, small scattered immunoreactive terminals are observed in the pars medianus, pars posterior and ventral region of the pars medialis of the medial mammillary nucleus. Larger labelled terminals are found in the pars lateralis, the dorsal region of the pars medialis of the medial mammillary nucleus and the lateral mammillary nucleus. At the ultrastructural level, GABA-immunoreactive synaptic endings in the different subdivisions of the medial mammillary nucleus exhibit a widespread somadendritic distribution. By contrast, GABA-immunoreactive terminals within the lateral mammillary nucleus are located predominantly in the neuropil and less frequently on neuronal somata. GABA-immunoreactive synaptic endings contain pleiomorphic synaptic vesicles and have symmetrical synaptic contact zones with the somata and dendrites in the lateral and medial mammillary nuclei. After in vivo inhibition of GABA metabolism with amino-oxyacetic acid, light microscopic examination of the mammillary nuclei reveals numerous small GABA-immunoreactive cells in various subdivisions of the medial mammillary nucleus. No immunoreactive cells are observed, however, in the lateral mammillary nucleus. Electron microscopic examination demonstrates that the GABA-immunoreactive cells are astrocytes. In the labelled astrocytes, immunohistochemical reaction product is localized throughout the nucleus and cytoplasm of the cells, in thin sheet-like processes surrounding neuronal elements and in end-feet lining the basal lamina of capillaries. The results indicate that the mammillary nuclei in the rat receive a strong GABAergic innervation. Most if not all, of the GABA-immunoreactive synaptic endings in the mammillary nuclei probably arise from extrinsic inhibitory sources. The possible sources of the GABA-immunoreactive input to the mammillary complex are discussed. PMID- 8515840 TI - Molecular profile of reactive astrocytes--implications for their role in neurologic disease. AB - The central nervous system responds to diverse neurologic injuries with a vigorous activation of astrocytes. While this phenomenon is found in many different species, its function is obscure. Understanding the molecular profile characteristic of reactive astrocytes should help define their function. The purpose of this review is to provide a summary of molecules whose levels of expression differentiate activated from resting astrocytes and to use the molecular profile of reactive astrocytes as the basis for speculations on the functions of these cells. At present, reactive astrocytosis is defined primarily as an increase in the number and size of cells expressing glial fibrillary acidic protein. In vivo, this increase in glial fibrillary acidic protein-positive cells reflects predominantly phenotypic changes of resident astroglia rather than migration or proliferation of such cells. Upon activation, astrocytes upmodulate the expression of a large number of molecules. From this molecular profile it becomes apparent that reactive astrocytes may benefit the injured nervous system by participating in diverse biological processes. For example, upregulation of proteases and protease inhibitors could help remodel the extracellular matrix, regulate the concentration of different proteins in the neuropil and clear up debris from degenerating cells. Cytokines are key mediators of immunity and inflammation and could play a critical role in the regulation of the blood central nervous system interface. Neurotrophic factors, transporter molecules and enzymes involved in the metabolism of excitotoxic amino acids or in the antioxidant pathway may help protect neurons and other brain cells by controlling neurotoxin levels and contributing to homeostasis within the central nervous system. Therefore, an impairment of astroglial performance has the potential to exacerbate neuronal dysfunction. Based on the synopsis of studies presented, a number of issues become apparent that deserve a more extensive analysis. Among them are the relative contribution of microglia and astrocytes to early wound repair, the characterization of astroglial subpopulations, the specificity of the astroglial response in different diseases as well as the analysis of reactive astrocytes with techniques that can resolve fast physiologic processes. Differences between reactive astrocytes in vivo and primary astrocytes in culture are discussed and underline the need for the development and exploitation of models that will allow the analysis of reactive astrocytes in the intact organism. PMID- 8515841 TI - The distribution of dystrophin in the murine central nervous system: an immunocytochemical study. AB - A mild non-progressive cognitive defect is a feature of the fatal X-linked disease, Duchenne muscular dystrophy. Recent studies have identified the genetic defect and the resulting loss of the protein dystrophin, and shown that dystrophin messenger RNA and protein are present in normal brain tissue. We have performed western immunoblotting and fluorescence immunocytochemistry using a sensitive antibody made against a large fragment of the dystrophin molecule to study the regional, cellular and subcellular distribution of dystrophin in the mammalian brain. The brains of B10 (control) and mdx (dystrophin deficient null mutant) mouse brain were compared on a point-by-point basis to verify that only dystrophin and not autosomal dystrophin related protein or cross-reacting proteins were being identified. In addition three murine neurologic mutants, nervous, lurcher, and weaver, were studied to refine the localization of dystrophin. In western immunoblots, dystrophin is present in all regions of the brain and in greatest abundance in the cerebellum. Dystrophin, as demonstrated in immunofluorescence, is present in neurons, but not in glia or myelin, and forms punctate foci associated with the plasma membrane of perikarya and dendrites, but not axons. While dystrophin is abundant in cerebral cortical neurons and cerebellar Purkinje cells, it is absent from most subcortical neurons, the granule cells of fascia dentata, and cerebellar neurons other than Purkinje cells. The absence of dystrophin in the cerebellum of the Purkinje cell deficient mutants nervous and lurcher, and its presence in the granule cell deficient mutant weaver indicate that dystrophin is a component of Purkinje cells rather than closely apposed afferents to those cells. The distribution and localization of dystrophin suggests a role in organizing the plasma membrane, possibly as an anchor of the postsynaptic apparatus, a possible basis for the cognitive defect in Duchenne dystrophy. PMID- 8515842 TI - Death of intermediolateral spinal cord neurons follows selective, complement mediated destruction of peripheral preganglionic sympathetic terminals by acetylcholinesterase antibodies. AB - Systemically injected anti-acetylcholinesterase antibodies in rats cause selective lesions of preganglionic sympathetic neurons. Adult rats were examined up to four months after a single i.v. injection of murine monoclonal acetylcholinesterase antibodies or normal immunoglobulin G (1.5 mg). Within 4 h, antibody-treated rats developed ptosis, a sign of sympathetic dysfunction that was never reversed. Persistent pupillary constriction reflected preserved and unopposed parasympathetic function. Weight gain was depressed, but locomotor activity, excitability, and sensorimotor responses were normal, and gross neuromuscular performance was near normal. These findings were supported by biochemical evidence for selective sympathetic damage. Acetylcholinesterase activity was reduced for the whole period of observation in sympathetic ganglia and adrenal glands but fell only transiently in muscle and serum. At all times, choline acetyltransferase activity (a marker of presynaptic terminals) was unaffected in muscle but grossly depleted in ganglia. Light and electron microscopy showed that preganglionic sympathetic terminals of superior cervical ganglia were severely damaged while parasympathetic ganglia were less affected and motor endplates of skeletal muscle were apparently spared. Immunocytochemistry revealed punctate deposits of murine immunoglobulin G and complement component C3 in ganglionic neuropil 12 h after antibody injection. This finding was consistent with complement-mediated lysis of preganglionic terminals. Morphometric analysis of preganglionic neurons in the intermediolateral nucleus of the spinal cord showed progressive loss of cholinergic perikarya over several months. We conclude that antibody-induced destruction of ganglionic terminals leads to death of preganglionic sympathetic neurons and, hence, permanent dysautonomia. PMID- 8515843 TI - Lesion of central cholinergic systems by systemically administered acetylcholinesterase antibodies in newborn rats. AB - To determine if systemically administered antibodies could reach antigenic targets and cause immunologic lesions in brains of newborn rats, murine monoclonal antibodies against rat acetylcholinesterase were injected i.p. on the first postnatal day. As early as 24 h after injection, antibodies were detected immunocytochemically in brain parenchyma, along with punctate debris that showed intense cholinesterase activity. Total acetylcholinesterase activity in the brain dropped by 30%, and 10S activity was almost undetectable at day 3, implying true enzyme loss since the antibodies did not directly impair catalytic function. At day 7, 10S acetylcholinesterase began to recover but the activity remained only half that of controls. At day 12, total acetylcholinesterase activity was still reduced (30% in whole brain, 40% in cerebral cortex), consistent with lasting damage to cholinesterase-expressing cortical neurons. This conclusion was confirmed by histochemical experiments showing a nearly complete disappearance of acetylcholinesterase fiber-staining in cerebral cortex and basal ganglia at days 4 and 8, with residual deficits at day 12. Choline acetyltransferase activity decreased in the cerebral cortex, implying a loss of cholinergic terminals, but specifically immunoreactive perikarya remained abundant in the basal forebrain. Immunocytochemistry showed no obvious changes in three non-cholinergic markers: tyrosine hydroxylase, tryptophan hydroxylase, and glutamic acid decarboxylase. Overall, it appeared that acetylcholinesterase antibodies induced widespread but reversible damage of cholinergic fibers and terminals, while sparing cholinergic cell bodies and many other neural systems. PMID- 8515844 TI - Nicotinic acetylcholine receptors in isolated type I cells of the neonatal rat carotid body. AB - Electrophysiological responses of enzymatically isolated type I cells from the neonatal rat carotid body to cholinergic agonists were examined using the whole cell patch-clamp technique. Inward currents were evoked in cells clamped at -70 mV in response to bath-applied carbachol and two selective nicotinic agonists, nicotine and dimethylphenylpiperazinium. Muscarine failed to produce any change in membrane current. Responses to nicotine were concentration-dependent and also voltage-dependent, showing strong rectification positive to -40 mV. Currents evoked by nicotine were reduced or abolished in the presence of mecamylamine and also by high concentrations of atropine (10 or 100 microM). Under "current clamp", nicotine was shown to depolarize type I cells, an effect which was only slowly reversible, but which could be rapidly attenuated by introduction of mecamylamine to the perfusate. In voltage-clamped cells, nicotine could evoke inward currents when extracellular Na+ was replaced by Ca2+. Our results demonstrate the presence of functional nicotinic acetylcholine receptors on type I cells of the neonatal rat carotid body. Activation of these receptors could lead to excitation of the intact carotid body by either of two possible mechanisms: depolarization of type I cells sufficient to open voltage-gated Ca2+ channels, or Ca2+ influx through the receptor pore itself. Either (or both) mechanisms could trigger catecholamine release from type I cells, which is a fundamental step in chemotransmission. PMID- 8515845 TI - Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons. AB - Slices of hippocampal area CA1 in the rat were employed to test the hypothesis that the activation of metabotropic glutamate receptors during tetanization is necessary for the late maintenance of long-term potentiation. If the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate was present during tetanization, post-tetanic and early long-term potentiation of the population spike as well as field excitatory postsynaptic potential developed almost normally. However, 100 min after tetanization, long-term potentiation of the field excitatory postsynaptic potential decreased in an irreversible manner. The same concentration of D-2-amino-3-phosphonopropionate was ineffective. If L-2 amino-3-phosphonopropionate was applied 120 min after tetanization, it did not influence long-term potentiation. The presence of the metabotropic glutamate receptor agonist trans-D,L-1-aminocyclopentane-1,3-dicarboxylic acid during tetanization weakly enhanced the slope of field excitatory postsynaptic potential long-term potentiation. The influence of L-2-amino-3-phosphonopropionate and D,L 1-aminocyclopentane-1,3-dicarboxylic acid on ionotropic glutamate receptors was studied using whole-cell voltage-clamp and pressure application techniques. No effect of L-2-amino-3-phosphonopropionate on either early or late components of excitatory postsynaptic currents could be detected at the concentration used to block long-term potentiation. It is therefore unlikely that the effect of L-2 amino-3-phosphonopropionate on long-term potentiation is due to an interaction with N-methyl-D-aspartate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. However, bath-applied 1S,3R-D,L-1-aminocyclopentane-1,3 dicarboxylic acid facilitated the N-methyl-D-aspartate-induced depolarization in response to N-methyl-D-aspartate pressure application in a reversible manner. These data suggest that besides the involvement of N-methyl-D-aspartate receptors the activation of a 2-amino-3-phosphonopropionate-sensitive metabotropic glutamate receptors during or immediately after tetanization is necessary for subsequent mechanisms responsible for the maintenance of long-term potentiation. A link between metabotropic glutamate receptors and protein kinase C activation during long-term potentiation is discussed considering the similar time course of long-term potentiation blockade after application of L-2-amino-3 phosphonopropionate and protein kinase C inhibitors. PMID- 8515846 TI - Latent inhibition of conditioned dopamine release in rat nucleus accumbens. AB - Classical conditioning both to rewarding and to aversive stimuli is sensitive to drugs which act on the dopaminergic system: amphetamine enhances conditioning and neuroleptics attenuate it. Many lines of evidence point to the nucleus accumbens as being part of an anatomical substrate for reward. We have examined the release of dopamine in the nucleus accumbens during classical aversive conditioning using microdialysis in the unrestrained rat. Two mild footshocks caused a release of dopamine, which was potentiated when each footshock was immediately preceded by a novel tone or light stimulus. Presentation of either of these stimuli after conditioning elicited an increase in dopamine, only to that stimulus which had been conditioned; presentation of either stimulus after footshock alone without conditioning produced no dopamine response. Latent inhibition is a process whereby pre-exposure to a stimulus without consequence impairs learning about that stimulus at subsequent conditioning. This process too is believed to be under the control of dopaminergic systems, particularly in nucleus accumbens. Pre exposure to the tone stimulus both markedly attenuated the potentiation of dopamine release at conditioning and abolished the conditioned release of dopamine at subsequent tone presentation. This is the first report of direct measurement of potentiated dopamine release during conditioning, and may provide a neurochemical basis for the effects of dopaminergic drugs on conditioning and latent inhibition. The results also support the hypothesis that disrupted latent inhibition in schizophrenia reflects increased mesolimbic dopamine function. PMID- 8515847 TI - Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze. AB - Transitory global cerebral ischaemia induced in rats by four vessel occlusion for 15 min produced substantial loss of CA1 cells in dorsal hippocampus, and minimal damage in other intra- and extrahippocampal forebrain regions examined. Ischaemic rats showed long-lasting deficits in spatial navigation in the water-maze, consisting of impaired learning to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Groups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, and from basal forebrain, containing cholinergic cells, with grafts sited in the alveus above the damaged CA1 region, for comparison with non-grafted ischaemic and non-ischaemic control groups, over a series of tests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a familiar pool in retention and reversal learning of the original platform position, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showed the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed marked impairment, whereas rats with CA1 grafts were significantly superior, and learned as rapidly as non ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptive use of spatial information, as shown by acquisition and working memory deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rats were tested in a novel environment, suggest that these grafts may have assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glutamatergic dentate granule grafts were ineffective. However, CA1 grafts showed better survival and growth than the other types of transplant, so that functional recovery may have been related to graft viability rather than to the specific type of graft. PMID- 8515848 TI - GABA and potassium effects on corticospinal and primary afferent tracts of neonatal rat spinal dorsal columns. AB - The neurotransmitter GABA markedly depresses action potential conduction in neonatal rat spinal dorsal columns. However, GABA sensitivity of the dorsal columns declines with maturation and myelination. At seven to 14 days after birth, the corticospinal tract component of the dorsal columns is immature and unmyelinated compared to the cuneate-gracilis fasciculi. GABA and isoguvacine (a GABAA receptor agonist) were applied to isolated neonatal (seven to 14 days old) dorsal columns during recordings of conducted cuneate-gracilis fasciculi and corticospinal tract action potentials. GABA (10(-4) to 10(-3) M) significantly reduced amplitudes (-28.9% to -69.7%) and increased latencies (+4.8% to +23.9%) of cuneate-gracilis fasciculi responses but had less effect on corticospinal tract response amplitudes (-1.1% to -14.7%) and latencies (+0.9% to +6.2%). Likewise, isoguvacine (10(-5) to 10(-4) M) reduced amplitudes (-26.7% to -37.5%) and increased latencies (+11.2% and +24.0%) of cuneate-gracilis fasciculi responses but had little or no effect on corticospinal tract response amplitudes (-6.2% to -3.8%) or latencies (-0.8% to +1.5%). At 10(-4) and 10(-3) M, GABA rapidly increased extracellular K+([K+]e) from baseline levels of 3.0 mM to 3.7 +/- 0.4 and 6.6 +/- 1.4 mM in cuneate-gracilis fasciculi and increased corticospinal tract [K+]e to 3.9 +/- 0.4 and 4.4 +/- 0.4 mM (mean +/- S.D.). [K+]e declined during drug application and fell below baseline after drug washout. Cuneate-gracilis fasciculi responses, however, did not recover until several minutes after [K+]e returned to baseline. In separate experiments, increasing bath [K+]e concentrations to 3.7 and 6.6 mM reduced cuneate-gracilis fasciculi response amplitudes by only -7.6% and -29.6%. Latencies increased by +1.3% and +3.6% respectively. The results indicate that the cuneate-gracilis fasciculi are more sensitive to GABA than the corticospinal tract and that the GABA effect is not entirely due to [K+]e changes. PMID- 8515849 TI - [Plasma levels of atriopeptin and hemodynamics during major vascular surgery: comparison between isoflurane and propofol+fentanyl]. AB - Atrial natriuretic factor (ANF) is a peptide hormone released from atrial cardiocytes in response to atrial stretch. It has potent and selective effects on vascular smooth muscle, fluid and electrolyte balance, and may interact with other vasoactive substances. The influence of anaesthesia and major vascular surgery on the release and circulation of ANF is unknown. Therefore the relationships between haemodynamic variables, volume expansion and plasma ANF were studied in patients undergoing resection of abdominal aortic aneurysm, randomly assigned to receive isoflurane or propofol+fentanyl anaesthesia. The end point of anaesthetic regimens was the stabilization of mean arterial pressure between +/- 33% from baseline. Haemodynamic parameters and plasma ANF levels were measured preoperatively, after intubation, following aortic cross-clamping, 24 and 48 hours postoperatively. Because of well-known large degree in interpatient pharmacodynamic variability, anaesthesia with propofol and fentanyl did not ensure, usually, the established end point in dose ranges that did not produce unacceptable morbidity. ANF plasma levels were elevated during surgery and in the immediate postoperative period in both groups. A significant correlation was found between ANF levels and mean right atrial pressure. We concluded that anaesthetic drugs do not affect ANF release. Volume expansion for prevention of declamping shock increased, ANF from basal values, during surgery. Inadequacy of postoperative analgesia or persisting atrial stretch could explain the finding of high plasma levels during the immediate postoperative period. PMID- 8515850 TI - [Comparison of ketorolac/buprenorphine in the treatment of post-cholecystectomy pain]. AB - The authors compared the efficacy of ketorolac trometamin (30 mg i.m. every 6 hours) and buprenorphine (0.3 mg i.m. every 12 hours) in the treatment of pain following cholecystectomy. Ketorolac was found to be equally efficacious in comparison to buprenorphine and caused fewer side effects. PMID- 8515851 TI - [A new approach to the brachial plexus: clinical results]. AB - The paper reports the results of a new brachial plexus blockade technique using a supraclavicular route which was carried out in 74 patients. From the analysis of results it can be seen that the technique is comparable to that of Moore and Winnie in terms of the success of the blockade. However, this technique appears to be safer in relation to complications such as pneumothorax and subarachnoid injection. PMID- 8515852 TI - [Psychologic implications in loco-regional anesthesia]. AB - A patients, who undergoes surgery, bears so stressful an emotional charge that his personality layout and life conflicts may emerge. When a patient is scheduled for loco-regional anaesthesia, the above mentioned issues should be taken into account to get a proper relation between the patient and the anaesthetist both in the pre- and intraoperative period. The following survey deals with psychological dynamics which compel the patient to ask for or reject a loco-regional anaesthetic procedure. Suggestions are also provided in order to manage adequately the anxiety and the hidden fears of the patient. PMID- 8515853 TI - [Drepanocytosis in patients undergoing heart surgery. Anesthesiologic problems]. AB - The authors report their experience with the management of patients with sickle cell trait undergoing open heart surgery. They focus their attention mainly on those factors potentially able to precipitate episodes of sickling, i.e. hypoxia, hypothermia, vascular stasis and acidosis. PMID- 8515854 TI - [A case of severe bronchospasm and laryngospasm after atracurium administration]. AB - We present a case of severe intraoperative bronchospasm and laryngospasm, that happened after the administration of atracurium 0.5 mg/kg-1; this episode was very difficult to manage, in spite of a prompt bronchodilative treatment. This episode of bronchospasm happened again after extubation and it was so severe that it was necessary to intubate the patient quickly again. We administered bronchodilatative drugs again, and after half an hour it was possible to extubate the patient and to send him to the ward. He had no problems in the postoperative period. We carried on some investigations to evaluate the nature of this reaction: we measured the level of IgE, C3 and C4 complement factor during operation (one sample), in the first and second postoperative days. Moreover we did an intradermal test for all the drugs used during the operation. We concluded that it was an anaphylactoid reaction, sustained by atracurium. PMID- 8515855 TI - [Practical device to reduce the tidal volume in mechanical ventilation, for neonatal and pediatric anesthesia]. AB - The authors propose a new device for controlled mechanical ventilation during general anaesthesia in pediatric and neonatal patients. This device can reduce TV delivered by an adult ventilator to small values. The device consists of: a small volume box (about 1.3 1); a disposable breathing circuit composed of a bag to put in the box, connecting tubes, a non rebreathing duckbill valve placed at the endotracheal tube; a monitoring system for pressure and expired volume. The authors tested the device according to ISO Standards. Performance during waveform tests and expiratory resistance agree with ISO request. During volume performance tests the device was able to deliver a minimum TV of 10 ml in all ISO Standard requested sets. PMID- 8515856 TI - [Body, muscle, and visceral nitrogen balance in catabolic patients. Modification with metabolic treatment]. AB - In sixteen severely catabolic patients, two different nutritional treatments with the same nitrogen input (0.30 gN.kg-1.die-1) but with a different caloric support: 30 kcal.kg-1.die-1 foe group A and 15 kcal.kg-1.die-1 for group B were infused. Body nitrogen balance (BN), muscle nitrogen balance (BNm) and, calculated as a difference of the two, visceral nitrogen balance were measured in every patient on basal day and on the second day of total parenteral nutrition. Both nutritional treatment reduced the catabolic state in the same amount: this was confirmed by a less negative body BN and by the reduced excretion of 3-MEH and amino acidic catabolic markers. Otherwise in the other compartments the treatments showed different effects: the metabolic support was more reduced by treatment A than it was by B, supplying to visceral compartment a lower nitrogen amount: the nitrogen dismission from muscle compartment, available for visceral tissues, is greater with treatment B than with treatment A. In conclusion, even if both treatments show the same effect on body nitrogen balance, they penalize either one of the examined compartment or the other. To avoid this problem, the study and the use of tissue-specific nutrients are desiderable. Tissue-specific solutions may warrant the balance among body compartment without any further increase of the nitrogen rate. PMID- 8515857 TI - [Nutritional support in patients with relapsing chronic respiratory failure]. AB - The authors review the scientific data on nutritional problems in patients with acute decompensation of COPD and present their own experience in the nutritional management of such condition. Artificial nutrition (enteral and parenteral) allowed a reduction in the duration of hospitalization, a lower incidence of infections, and a shorter weaning time from mechanical ventilation in comparison to a homogeneous group of patients treated in the same unit in an earlier period, when less attention was paid to nutritional problems. The importance of artificial nutrition in patients with acute decompensation of COPD is highlighted. PMID- 8515858 TI - [Anesthesia in thymectomy. Experience with 115 cases]. AB - The authors have conducted a retrospective study on 115 patients with myasthenia gravis undergoing transsternal or transcervical thymectomy at the Policlinico A. Gemelli of Rome in the period June 1984- to June 1991. A prolonged postoperative mechanical ventilation immediately and a few days following surgery was required respectively in 7 and 3 patients, while atelectasia and broncopneumonia have developed in 10 patients. No relationship could be established between the incidence of respiratory complications and factors such as preoperative symptomatology and treatment anesthetic agents, the surgical approach to the thymus and thymic pathology. However a significantly greater postoperative morbidity has been observed in the group of patients receiving suxametonium as compared to the patients receiving non-depolarizing muscle relaxants. Vecuronium and atracurium very frequently allowed ad adequate resumption of spontaneous respiration after anesthesia and made possible a safe early extubation of patients before leaving the operating room. The authors also stressed that all patients, irrespective of their clinical conditions, must be transferred after thymectomy. Oto the surgical ICU where anticholinesterase therapy can be safely restarted and cardiorespiratory status carefully monitored. PMID- 8515859 TI - The hypophagic effect of restraint stress in rats can be mediated by 5-HT2 receptors in the paraventricular nucleus of the hypothalamus. AB - Ritanserin (0.5 and 1 mg/kg) and ketanserin (2.5 mg/kg), two antagonists with high affinity for 5-HT2 receptors, attenuated restraint stress-induced hypophagia in rats. Two injections of the 5-HT2 receptor antagonist cinanserin (30 nmol/0.5 microliter) in the paraventricular nucleus of the hypothalamus completely reversed the effect of stress on food intake. (+/-)Cyanopindolol (3 and 8 mg/kg), an antagonist at 5-HT1A and 5-HT1B receptors, had no effect whereas 8-hydroxy-2 di-n-propylamino)tetralin (30-300 micrograms/kg), an agonist at 5-HT1A receptors, significantly attenuated the hypophagia. The results suggest that restraint stress-induced hypophagia is mediated by 5-HT2 receptors in the paraventricular nucleus of the hypothalamus. The potential utility of this model in anorexia nervosa is discussed. PMID- 8515860 TI - Effects of polyamines on NMDA-induced currents in rat hippocampal neurons: a whole-cell and single-channel study. AB - Actions of the polyamines spermine and spermidine on NMDA-induced currents were examined in cultured hippocampal neurons from embryonic rat. In whole-cell patch experiments using voltage-clamp, spermine (300 microM) produced about a two-fold potentiation of responses to NMDA (at -70 mV in the presence of saturating glycine); half-maximal potentiation was elicited at 207 microM. The potentiation produced by spermine was somewhat greater at positive potentials. The onset of potentiation was fast (t1/2 < 1 s), indicative of an extracellular site of action. Spermidine was of comparable potency but less efficacious than spermine in potentiating NMDA responses. In excised outside-out patches, spermine exhibited two actions on NMDA-induced single-channel responses. In some patches, it increased the channel open probability; both frequency of channel opening and burst length were increased with no significant change in the mean open duration, which accounted for much of the potentiation seen in whole-cell experiments. In all patches, spermine decreased channel conductance at negative voltages, an effect ascribable to fast channel block (with a possible contribution by charge screening). These results are consistent with opposing actions of polyamines mediated at distinct sites on the NMDA receptor. PMID- 8515861 TI - Protective effect of deprenyl against 1-methyl-4-phenylpyridinium neurotoxicity in rat striatum. AB - Rats were treated with deprenyl for 3 weeks. Afterwards, slices of the corpus striatum were incubated with 1-methyl-4-phenylpyridinium ion (MPP+). Concentrations of dopamine and its metabolite concentrations were assayed. The effect of MPP+ in animals treated with deprenyl was smaller than in controls, indicating that deprenyl protects against MPP+. We also measured superoxide dismutase (SOD) and catalase activities and carbonyl group content of the proteins. Both activities increased in deprenyl-treated rats, and the amount of carbonyl groups was unchanged. These results suggest that the protective effect of deprenyl is independent of the monoamine oxidase-B inhibitor and of the induction of SOD and catalase activities. PMID- 8515862 TI - Conditioning of histamine by bradykinin alters responses of rat nociceptor and human itch sensation. AB - The effect of a conditioning bradykinin application on histamine induced excitation of cutaneous nociceptors and on histamine induced sensations of volunteers was studied. Using an in vitro skin nerve preparation, unmyelinated polymodal nociceptor units of rats (n = 11) were tested by bathing their receptive fields from the corium side with 10(-5) M solutions of bradykinin and histamine. Following bradykinin superfusion the histamine induced discharges were enhanced, and previously unresponsive units were excited by histamine. Corresponding psychophysical experiments were carried out in 13 healthy volunteers. Histamine iontophoresis (30 mC) induced predominantly itching sensations after an intracutaneous control injection of physiological saline. However, following bradykinin injections (100 microliters of a 10(-7) M solution) histamine induced little itch but rather a burning sensation lasting 1-2 min. Itching remained suppressed even after the burning sensations had subsided. These data support a hypothesis according to which itching is mediated by a sub population of polymodal nociceptor units, and pain is induced whenever a larger nociceptor population is recruited. In the CNS itch processing is either occluded (masked) by pain processing, or suppressed by inhibitory processes. PMID- 8515863 TI - Daily variations in concentration of vasoactive intestinal peptide immunoreactivity in hypothalamic nuclei of rats rendered diurnal by restricted schedule feeding. AB - We previously described that in the suprachiasmatic (SCN), peri-(PeVN) and paraventricular (PaVN) nuclei of normal rats, vasoactive intestinal peptide (VIP) like immunoreactivity (VIP-LI) accumulates during the night period and decreases during the day. In order to determine whether these variations are linked to the light-dark cycle or are a consequence of sleep-wake rhythm expression, we dissociated these two parameters by restricting feeding to diurnal hours. In these conditions which inverse the paradoxical sleep rhythm, the VIP-LI pattern is perturbed and its minimum advanced by 4 h in the SCN. In the PeVN, the daily pattern is maintained but the minimum is also advanced by 4 h. Finally, the rhythm is abolished in the PaVN. These circadian fluctuations indicate that the hypothalamic VIP-LI rhythm is not linked to the paradoxical sleep rhythm but could be sensitive to photic and non-photic Zeitgeber. PMID- 8515864 TI - Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat. AB - We examined the distribution of mRNA for the peptide cholecystokinin (CCK) with in situ hybridization in adult rat lumbar dorsal root ganglia following unilateral section of the sciatic nerve, as well as the effect of systemic CI 988, a selective antagonist of the CCK type B receptor, applied alone or in combination with intrathecal (i.t.) morphine, on the self-mutilating behavior of rats (autotomy) after axotomy, a sign of neuropathic pain and/or dysesthesia. There was a dramatic increase in the number of neurons in dorsal root ganglia synthesizing the peptide cholecystokinin (CCK) after sciatic nerve section. Furthermore, the autotomy behavior of rats was significantly inhibited by chronic i.t. administration of morphine in conjunction with subcutaneous (s.c.) injection of CI 988. Neither i.t. morphine nor s.c. CI 988 alone produced a comparable effect on autotomy. Our results suggested that up-regulation of the mRNA for CCK in primary afferents after nerve injury may be related to the clinical phenomenon of opioid insensitivity. Thus, coadministration of CCK antagonists in combination with opioids may offer a new approach in treating neuropathic pain. PMID- 8515865 TI - Homomeric assemblies of NMDAR1 splice variants are sensitive to ethanol. AB - Studies have shown that the neuronal NMDA receptor is a target for the actions of ethanol. Recently, a number of subunits of the NMDA receptor have been cloned and functionally expressed in various combinations. We have expressed four splice variants of the NMDAR1 subunit in Xenopus oocytes, and find that homomeric assemblies of this subunit, in the absence of other subunits, exhibit ethanol sensitivity comparable to that seen in neurons. In the presence of calcium, the reduction of total current was greatest in the NMDAR1-LL splice variant, and was significantly less in the NMDAR1-SS variant. The increased sensitivity of NMDAR1 LL may be attributed to a particularly sensitive slow current 'hump' which is more pronounced in NMDAR1-LL than in NMDAR1-SS. The reduction of NMDA-evoked current by ethanol was significantly different when calcium was replaced by barium in the external medium. In this case, the slow current hump was significantly reduced, current through NMDAR1-LL was less reduced by ethanol, and the percent reduction of NMDAR1-LL and NMDAR1-SS currents was similar. NMDA evoked currents in heteromeric receptors formed by coinjection of the mouse epsilon-1 subunit with the NMDAR1 splice variants responded to ethanol similarly to homomeric assemblies. PMID- 8515866 TI - The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons. AB - Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form. PMID- 8515867 TI - Spinal pathways mediate coordinated bladder/urethral sphincter activity during reflex micturition in decerebrate and spinalized neonatal rats. AB - Coordination between the urinary bladder and the external urethral sphincter is necessary for normal voiding. However, it is uncertain whether the spinal cord or brainstem generates this coordination. Bladder and urethral sphincter activity were examined during reflex voiding induced by perineal stimulation or bladder distension in decerebrate non-spinalized and spinalized 15 to 26-day-old neonatal rats. Perineal stimulation induced voiding and coordinated bladder/sphincter activity in both types of rats, indicating that spinal pathways can generate coordinated voiding behavior. The discoordination observed during voiding induced by bladder distension in spinalized pups may be due to the loss of descending pathways or to the emergence of detrimental spinal reflexes. PMID- 8515868 TI - Calretinin-immunoreactive neocortical interneurons are unaffected in Alzheimer's disease. AB - Recent studies have revealed that select neuronal populations may display a differential sensitivity to degeneration in Alzheimer's disease. For example, large pyramidal neurons have been shown to be vulnerable, whereas small, local circuit neurons appear to be resistant to the pathologic process. More significantly, interneurons that contain the calcium-binding proteins parvalbumin and calbindin are particularly resistant to degeneration in Alzheimer's disease. Using a polyclonal antibody to the calcium-binding protein calretinin, we analyzed the possible changes in the subset of interneurons containing this protein in two neocortical areas that are generally devastated in Alzheimer's disease. In the prefrontal cortex as well as in the inferior temporal cortex, we observed no difference in the density of calretinin-immunoreactive neurons in Alzheimer's disease brains as compared to control cases. Moreover, the cellular morphology of these neurons was well preserved in the Alzheimer's disease cases. These data suggest that calretinin-immunoreactive neurons, like other calcium binding protein-containing interneurons, are resistant to degeneration in Alzheimer's disease. The results support the notion that the pathological process in Alzheimer's disease involves specific cellular populations sharing particular morphological and neurochemical characteristics. In addition, it is possible that the presence of calcium-binding proteins confers a certain degree of resistance to degeneration in specific neuronal subsets. PMID- 8515869 TI - The protein VAT-1 from Torpedo electric organ exhibits an ATPase activity. AB - VAT-1 is an abundant protein in Torpedo electric organ which copurifies with a major ATPase activity from synaptic vesicles. VAT-1 was expressed in E. coli and the product was purified and analyzed. The protein binds specifically to an ATP column and displays an ATPase activity as measured by the kinetics of [32P]phosphate release. The activity is dependent on divalent ions, with both Mg2+ and Ca2+ supporting the reaction. The apparent Km for ATP is 18 microM. This ATPase activity is not affected by known inhibitors of the vesicular V- and P type ATPases such as vanadate and N-ethylmaleimide. We suggest that VAT-1 activity may affect ATP-dependent reactions in Torpedo nerve terminals, such as phosphorylation and dephosphorylation of proteins. PMID- 8515870 TI - Neuropeptide Y innervation in the spinal nucleus of bulbocavernosus of the rat. AB - Immunoelectron microscopy combined with a retrograde tracing technique was carried out to examine the synaptic interaction between neuropeptide Y (NPY)-like immunoreactive (LI) axon terminals and spinal motoneurons innervating bulbocavernosus muscles. Cell bodies and proximal dendrites of these motoneurons were frequently found to receive synaptic inputs from NPY-LI axon terminals. PMID- 8515871 TI - Alternatively spliced isoforms of the NMDAR1 glutamate receptor subunit: differential expression in the basal ganglia of the rat. AB - Several isoforms of the NMDAR1 glutamate receptor subunit are produced by alternative mRNA splicing of three cassette sequences. Using in situ hybridization with exon-specific probes, we have observed differential regional expression of a cassette in the amino terminus of the NMDAR1 subunit, Insertion I, which confers distinct structural and physiologic properties. The differential distribution of expression is most prominent in the basal ganglia, where only the subthalamic nucleus expresses the insertion at high levels. PMID- 8515872 TI - The preventive effect of cyclosporin A, an immunosuppressant, on the late onset reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia. AB - We previously reported that a late onset reduction of muscarinic acetylcholine receptors (LORMAR) occurs in the gerbil hippocampus after 5 min of transient ischemia. This reduction begins as late as 7 days post-ischemia and accompanies the accumulation of glia, but is subsequent to completion of the disappearance of CA1 pyramidal cells. In the present study, we showed that this LORMAR was prevented by daily post-ischemic administration of the immunosuppressant cyclosporin A (CsA). The effectiveness of CsA against the LORMAR indicates that an immune mechanism may be involved in the progressive brain damage occurring after transient ischemia. PMID- 8515873 TI - Cocaine levels in striatum and nucleus accumbens: augmentation following challenge injection in rats withdrawn from repeated cocaine administration. AB - There is general agreement that the brain level of cocaine achieved in response to an intraperitoneal (i.p.) cocaine challenge is higher in animals that have been treated repeatedly with cocaine. However, whether this change in drug disposition persists following withdrawal from repeated treatment is controversial. Rats received either single or repeated injections of cocaine (10 mg/kg, i.p.), and levels of cocaine were measured in dorsal striatum and nucleus accumbens 20 min after the last injection. Cocaine levels were 60-70% higher in both brain regions of rats that had been treated with cocaine once daily for 7 days compared to rats that had received only a single injection. On the 7th day of withdrawal, similar elevations were observed after a challenge injection of cocaine in animals that had been treated repeatedly with cocaine but not in animals that had been treated repeatedly with saline. This persistent pharmacokinetic change should be taken into account in studies of cocaine-induced behavioral sensitization. PMID- 8515874 TI - Aging enhances the calcium sensitivity of central neurons of the mouse as an adaptive response to reduced free intracellular calcium. AB - Age-related changes in Ca(2+)-homeostasis have been investigated in mechanically dissociated neurons from young and aged mice. In aged animals, basal intracellular calcium ([Ca2+]i) was significantly reduced and depolarization (KCl)-induced rise in [Ca2+]i was lower, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca2+ influx. Additionally, depolarization-induced inositol-phosphate (IP) accumulation in aged animals was found to be significantly increased. Both findings suggest that Ca(2+)-dependent intracellular processes become more sensitive to Ca2+ in aged animals due to decreased Ca2+ availability. PMID- 8515875 TI - Processing of the beta-amyloid precursor protein carrying the familial, Dutch type, and a novel recombinant C-terminal mutation. AB - Mutations within the beta-amyloid precursor protein (beta-APP) gene that cosegregate with early onset familial Alzheimer's disease (FAD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch-type (HCHWA-D) have been reported. The effects of these mutations on the products of both the non amyloidogenic and potentially amyloidogenic processing pathways of the beta-APP protein were examined in stably transfected cells. Processing of these mutants appeared to be the same as wild-type. These results contrasted sharply to those observed with a mutation near the amino terminus of the beta-protein domain of beta-APP. This mutation resulted in a two-fold decrease of a potentially amyloidogenic 11 kDa peptide fragment. The data suggest that the FAD and HCHWA-D mutations have no effect on the formation of potentially amyloidogenic fragments in this cell system, possibly implicating an alternative mechanism for their effects. PMID- 8515876 TI - On the expression of Fos-like protein in the subthalamic nucleus and basal ganglia output systems following kainic acid injections into the rodent striatum. AB - By immunohistochemistry, Fos-like protein induced in response to intrastriatal kainic acid injections was explored in the basal ganglia and the ventrolateral thalamic nucleus of the rat. In the globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata, subthalamic nucleus and ventrolateral thalamic nucleus, Fos was expressed in neuronal cell nuclei showing the maximal number at 4 h and disappeared within 48 h. The substantia nigra pars compacta neurons lacked prominent Fos induction, suggesting that a different mechanism may operate for changes of dopamine systems. Concurrent Fos expression noted in selected regions suggests the link of relay and output stations of the basal ganglia with the ventrolateral thalamus at the early stage of striatal cell degeneration. PMID- 8515877 TI - Prominent expression of the actin-sequestering peptide Fx gene in the hippocampal region of rat brain. AB - We have analyzed by in situ hybridization the distribution of Fx (an actin sequestering peptide) mRNA in the brain of young and old rats. The strongest Fx mRNA-specific hybridization signal was located in the hippocampo-entorhinal cortex; this mRNA was also found in the piriform cortex, amygdala, lateral septum and neocortex. Northern blot analysis confirmed the prominent expression of the Fx transcript in the hippocampus and showed a notably lower amount of this mRNA in the hippocampus of old rats suggesting an influence of aging on the expression of this gene. The possible implication of Fx in synaptic plasticity and in long term potentiation is discussed. PMID- 8515878 TI - Neurotensin immunoreactivity in the colliculus inferior of cat: light and electron microscopic investigations. AB - Neuronal perikarya with neurotensin-like immunoreactivity (NT-LI) are found in the pericentral and external nuclei and the dorsomedial part of the central nucleus of the inferior colliculus. On electron-microscopic examination, these neurons are characterized by a relatively large nucleus, a small amount of cytoplasm and paucity of organelles. NT-LI is observed in large and small dendrites and dendritic spines as well as in axon terminals which contain small round or elongated clear vesicles and/or dense core vesicles. The immunoreactive terminal boutons make asymmetrical axodendritic and symmetrical axo-somatic synapses mainly on non-immunoreactive elements. PMID- 8515879 TI - Coupling of grip force and load force during arm movements with grasped objects. AB - Numerous studies have investigated the kinematics of arm movements; others have examined grip forces during static holding of objects. However, the coordination of grip force and arm movement when moving grasped objects has not been documented. We show that grip force is finely modulated in phase with load force during movements with grasped objects in which load force varies with acceleration. A tight coupling between grip and load force is seen in point-to point and cyclic movements of varying rate and direction. We conclude that in transporting an object, the programming of grip force is part and parcel of the process of planning the arm movement. PMID- 8515880 TI - Neurite outgrowth of neurons of rat dorsal root ganglia induced by new neurotrophic substances with guanidine group. AB - In order to search for compounds mimicking the neurotrophic activities, a series of substances possessing the guanidine group of isaxonine (2-isopropylamino pyrimidine), were synthesized and tested for their ability to induce neurite outgrowth in cultures of explants of rat dorsal root ganglia. It is reported that several of these compounds, at concentrations ranging from 10(-5) to 10(-7) M, showed important effects on neurite outgrowth in vitro, similar to that obtained with the nerve growth factor NGF. These effects were found to be additive to that of NGF. PMID- 8515881 TI - Spreading depression can be restricted to distinct depths of the rat cerebral cortex. AB - In cerebral cortex of rats recurrent and single spreading depressions (SDs) were elicited by KCl application and by needle prick, respectively. SDs were monitored by recording changes of DC (direct current) potentials and of K+ concentration ([K+]o) in the extracellular space using K(+)-selective microelectrodes. Profiles of DC potential and of [K+]o were obtained by stepwise lowering a microelectrode array consisting of up to four electrodes into the brain cortex. Recurrent SDs propagating from the site of KCl application had lower frequencies and longer duration in superficial compared to deeper cortical structures. Single SD elicited by needle prick 3 mm away from the recording sites usually invaded the whole grey matter and showed DC potential shifts that differed in shape from the recurrent SDs. At a depth restricted to 1000 microns SD-related DC potential shifts and rises in [K+]o were drastically diminished. In 2 of 8 experiments prick-elicited SD was absent either above or below cortical depths of 800-1000 microns. The results suggest a barrier for vertical SD propagation in cortical depth between 800 and 1200 microns. The observations are relevant for application of noninvasive techniques (DC electroencephalography, magnetoencephalography) to detect SD in the brain. PMID- 8515882 TI - Desensitization of embryonic nicotinic acetylcholine receptors expressed in Xenopus oocytes. AB - Xenopus oocytes where injected with mRNA coding for the embryonic type of the bovine nicotinic acetylcholine receptor (nAChR). Pulses of acetylcholine (ACh) were applied to outside-out patches of the injected oocytes with the liquid filament switch. With high concentrations of ACh (10(-3) M), the ACh response desensitized rapidly; the decay could be fitted with a single exponential with a time constant of about 50 ms. In double pulse experiments, recovery from desensitization was tested. Complete recovery was observed after 5 s. The affinity of ACh to the desensitized receptor was measured by preincubating the outside-out patch with different concentrations of ACh. Preincubation with 10(-6) M ACh led to complete desensitization of the nAChRs on the patch. The results can be fitted with the molecular scheme describing activation and desensitization of the nAChR which was developed recently for embryonic nAChRs of mouse muscle. PMID- 8515883 TI - Response diversity of pontine and deep cerebellar nuclear neurons to air puff stimulation of the eye in the alert cat. AB - The discharge of antidromically identified brainstem and cerebellar nuclear neurons involved in the corneal reflex was recorded in the alert cat during corneal air puffs. Eye movements were measured with the search coil technique. Recorded sensory, motor, reticular formation and cerebellar nuclear neurons showed a wide diversity in latencies and patterns of response to air puff stimulation. This diversity suggests that each part of the circuit may contribute different properties to information processing for the corneal reflex, for sustained eyelid closure and, possibly, for the classical conditioning of the nictitating membrane response. PMID- 8515884 TI - Calbindin D-28K distribution in the retina of the developing trout (Salmo fario L.). AB - The appearance of calbindin D-28K, a calcium-binding protein, during development of the trout retina was studied by immunohistochemistry. The first calbindin immunoreactive cells appear in the inner nuclear layer at the equator of the embryonic retina at the stage 227 degrees C (around embryonic day 15). Just before hatching, stage 440 degrees C (around embryonic day 30) cells located in the ganglion cell layer and inner nuclear layer, expressed calbindin. This pattern of immunoreactivity was conserved in post-embryonic retinae (alevins 15 days old). In adult retinae the ganglion cells showed a faint immunoreaction; the amacrine cells are markedly fewer and their immunoreaction declined; and the bipolar cells expressed calbindin for the first time. The results obtained in the present work attending to the expression of calbindin, generally conforms with the vitreal to scleral progression of differentiation of the teleost retina. Ganglion, amacrine and bipolar cells undergo further maturation after beginning calbindin expression. PMID- 8515885 TI - Mutation of the gene for the human lysosomal serine protease cathepsin G is not the cause of aberrant APP processing in familial Alzheimer disease. AB - Recent genetic linkage studies have implicated a gene on chromosome 14 in the pathogenesis of FAD. The identity of this gene remains unknown but it has been speculated that it may be involved in the cellular processing of the amyloid precursor protein (APP). We have analyzed the nucleotide sequence of the entire open reading frame of the cathepsin G gene located on chromosome 14q. No mutations were observed, suggesting that defects in this lysosomal protease are not responsible for aberrant accumulation of proteolytic products of APP in FAD brain tissue. PMID- 8515886 TI - Mandatory nutrition labeling--FDA's final rule. PMID- 8515887 TI - Vitamin/mineral supplementation, the aging immune response, and risk of infection. AB - Immunological vigor declines with age, contributing to increased morbidity and mortality in the elderly. In addition, the elderly are at greater risk for low intake of several vitamins and minerals known to influence the immune response. Recent studies have shown that supplementing the elderly with single nutrients or mixtures of vitamins and minerals at levels that exceed the Recommended Dietary Allowances (RDAs) significantly improves certain indices of the immune response. In one study, improved immune response was associated with decreased frequency of infectious diseases, indicating that nutrient-induced immunological improvement clinically enhances the health of the elderly. PMID- 8515888 TI - Does dietary calcium supplementation reduce the risk of colon cancer? AB - Several recent studies have examined the hypothesis that calcium supplementation (1.2-2.0 g/day) protects against colon cancer in persons at high risk. The effect of supplementation was assessed by comparing the labeling index of rectal biopsy specimens before and after supplementation. Although in most studies the labeling index tended to decrease during supplementation, the results were inconsistent. It is also unclear whether the decrease in the index correlates with a decrease in occurrence or recurrence of colonic tumors. Use of calcium prophylaxis for persons at risk for colon cancer should be reserved for controlled clinical trials. PMID- 8515889 TI - Are we at risk for heart disease because of normal iron status? AB - A recent prospective three-year follow-up study of 1931 men in Finland demonstrated a significant 2.2-fold greater risk of acute myocardial infarct in 42- to 60-year-old men who had serum ferritin concentrations above 200 micrograms/dL. However, the mean plasma ferritin concentration in this population was high and the prevalence of hemochromatosis was unknown; these issues mitigate the suggestion that high-normal iron stores leads to heart disease. PMID- 8515890 TI - Recommendations dealing with nutrition and relief operations in times of disaster. PMID- 8515891 TI - The International Conference on Nutrition: a nongovernmental perspective. PMID- 8515892 TI - The International Conference on Nutrition: giving nutrition a human face. PMID- 8515893 TI - Amino acid nutrition: a two-step absorptive process. AB - A linkage between intestinal and tissue absorption of amino acids was perceived by Donald D. Van Slyke and Gustave M. Meyer in 1913, but soon overlooked by later authors. Today, on the 110th anniversary of Van Slyke's birth and the 80th anniversary of publication of their now-classic paper in the Journal of Biological Chemistry, the observation gains in nutritional significance and tells us, incidentally, why we should not dose ourselves with an isolated amino acid. PMID- 8515894 TI - There are more causes of TSS than tampon use. PMID- 8515895 TI - NPs don't need doctors' directions to make decisions about nursing care. PMID- 8515896 TI - Looking toward an NP/CNS merger by the year 2010. PMID- 8515897 TI - The critical role of exercise in weight control. AB - Exercise appears to play a critical role in the loss and maintenance of body weight. Diet alone has met with only temporary success because metabolic rate is decreased with extreme calorie restriction. This decrease persists after the dieting period has ended, often leading to rapid weight regain and the "yo-yo effect." In some instances, exercise alone has been effective for weight loss; however, success varies according to the gender of the subjects and to the type, intensity and duration of the exercise. Exercise programs of low to moderate intensity, long duration and high frequency seem to be most beneficial, with the most popular forms of exercise being walking/jogging, cycling and swimming. The purpose of this article is to explore the differences between diet and exercise, low vs. high intensity, short vs. long duration, and land vs. water exercise as these differences pertain to weight loss, food intake and energy balance. PMID- 8515898 TI - Understanding, eliciting and negotiating clients' multicultural health beliefs. AB - People of many cultures explain and treat illness in ways that are different from and that may conflict with the biomedical beliefs and practices on which the American health care system is based. Eliciting clients' health beliefs and negotiating treatment plans with them can help avoid problems caused by discrepancies in belief systems. This article presents three major categories of belief systems commonly found in the United States as well as other countries. Questions designed to discover clients' health beliefs are included, along with guidelines for arriving at plans of care that accommodate those beliefs. Case studies are provided that illustrate this process of negotiation. PMID- 8515899 TI - Assessment and management of the client with headaches. AB - Headaches are considered the most common type of pain; more than 40 million Americans seek medical help each year for this complaint. In order to adequately assess and manage the client with headaches, a clear understanding of the types and possible causes of this pain is essential. The purpose of this article is to provide information to assist the primary care practitioner in this process. Headaches can be categorized as either primary or secondary to an underlying (and usually treatable) problem. Most headaches fall into the primary group, which includes migraine (and variants), cluster and tension-type headaches. However, headaches secondary to an underlying cause must be identified so that further investigation, treatment and/or referral may be initiated. Several reference tables are included with this article to aid in the identification of the causes of headaches and to assist with the assessment and management of the client with this complaint. A headache questionnaire is also included to help facilitate this process. PMID- 8515900 TI - Pro- and anticonvulsant effects of stress: the role of neuroactive steroids. AB - The present review deals with findings related to the contribution of pro- and anticonvulsant effects of "neuroactive" steroids and the role of the gamma aminobutyric acid (GABA) receptor as a physiological target for naturally occurring steroids. Ways are discussed via which GABAergic neurotransmission can be enhanced or reduced following maneuvers that inflict stress. The duality of stress effects is emphasized in conjunction with different types of epileptogenesis (e.g., grand mal vs petit mal) that undergo dissimilar evolution. Among the issues covered are steroid-induced sedation and epileptogenicity, excitatory steroids, stress and epilepsy, GABA and respiratory functions, asymmetric brain injury, and psychopathology and stress. PMID- 8515901 TI - The lateral hypothalamic area revisited: neuroanatomy, body weight regulation, neuroendocrinology and metabolism. AB - This article reviews findings that have accumulated since the original description of the syndrome that follows destruction of the lateral hypothalamic area (LHA). These data comprise the areas of neuroanatomy, body weight regulation, neuroendocrinology, neurochemistry, and intermediary metabolism. Neurons in the LHA are the largest in the hypothalamus, and are topographically well organized. The LHA belongs to the parasympathetic area of the hypothalamus, and connects with all major parts of the brain and the major hypothalamic nuclei. Rats with LHA lesions regulate their body weight set point in a primary manner and not because of destruction of a "feeding center". The lower body weight is not due to finickiness. In the early stages of the syndrome, catabolism and running activity are enhanced, and so is the activity of the sympathetic nervous system (SNS) as shown by increased norepinephrine excretion that normalizes one mo later. The LHA plays a role in the feedback control of body weight regulation different from ventromedial (VMN) and dorsomedial (DMN). Tissue preparations from the LHA promote glucose utilization and insulin release. Although it does not belong to the classical hypothysiotropic area of the hypothalamus, the LHA does affect neuroendocrine secretions. No plasma data on growth hormone are available following electrolytic lesions LHA but electrical stimulation fails to elicit GH secretion. Nevertheless, antiserum raised against the 1-37 fragment of human GHRF stains numerous perikarya in the dorsolateral LHA. The plasma circadian corticosterone rhythm is disrupted in LHA lesioned rats, but this is unlikely due to destruction of intrinsic oscillators. Stimulation studies show a profound role of the LHA in glucose metabolism (glycolysis, glycogenesis, gluconeogenesis), this mechanism being cholinergic. Its role in lipolysis appears not to be critical. In general, stimulation of the VMN elicits opposite effects. Lesion studies in rats show altered in vitro glucose carbon incorporation into several tissue fractions both a few days, and one mo after lesion production. Several of these changes may be due to the reduced food intake, others appear to be due to a "true" lesion effect. PMID- 8515902 TI - Animal models of Alzheimer's disease: glutamatergic denervation as an alternative approach to cholinergic denervation. AB - Alzheimer's disease (AD) is a neurodegenerative disorder that severely reduces lifespan. In this article, a new, glutamatergic denervation model of AD is presented as a supplement to the well known cholinergic one, because these models are trying to mimic different aspects of the pathology in AD. Impaired memory and disorientation are prominent features in the symptomatology of AD. In searching for neurochemical systems associated with the initial cognitive disorders of AD, a reorientation from cholinergic to glutamatergic systems is suggested. Results from recent behavioral studies of damage to the temporal and entorhinal cortices in rats imply that these structures are strongly involved in mnemonic function. Findings from Alzheimer brains and laboratory animals indicate that major losses of glutamatergic receptors may underly the cognitive impairment seen in AD patients. A growing body of evidence appears to support a glutamatergic hypothesis of AD. Possible pharmacological approaches are suggested. PMID- 8515903 TI - Pharmacological modulation of soman-induced seizures. AB - Anticholinergics, benzodiazepines and N-methyl-D-aspartate (NMDA) antagonists have been shown to modulate the expression of nerve agent-induced seizures. This study examined whether the anticonvulsant actions of these drugs varied depending on the duration of prior seizure activity. Rats implanted with electrodes to record electroencephalographic (EEG) activity were pretreated with the oxime HI-6 (125 mg/kg, IP) to prolong survival, and then challenged with a convulsant dose of the nerve agent soman (180 micrograms/kg, SC); treatment compounds (scopolamine, diazepam, MK-801, atropine, benactyzine, and trihexyphenidyl) were delivered IV at specific times after seizure onset. Both diazepam and MK-801 displayed a similar profile of activity: At both short or long times after seizure initiation the anticonvulsant efficacy of each drug remained the same. Diazepam, and especially MK-801, enhanced the lethal actions of soman by potentiating the respiratory depressant effects of the agent; scopolamine given prior to diazepam or MK-801 protected against the respiratory depression. Scopolamine and atropine showed a dose- and time-dependent effectiveness; the longer the seizure progressed the higher the dose of drug required to terminate the seizure, with eventual loss of anticonvulsant activity if the seizure had progressed for 40 min. In contrast, benactyzine and trihexyphenidyl showed a third profile of activity: There was a smaller increase in drug dosage required for anticonvulsant activity as seizure duration increased, and both drugs could terminate seizures that had progressed for 40 min. The early anticonvulsant action of anticholinergics is interpreted as a specific effect that blocks the primary cholinergic excitatory drive that initiates, and first maintains, nerve agent seizures. If allowed to progress, the seizure activity itself recruits excitatory neurotransmitter systems (i.e., NMDA) that eventually maintain the seizure independent of the initial cholinergic drive. This is indicated by the eventual ineffectiveness of scopolamine and atropine as the duration of the seizure progresses. Diazepam and MK-801 appear to act to moderate nerve agent seizures by enhancing inhibitory activity (diazepam) or dampening the secondarily activated noncholinergic excitatory system (MK-801). Benactyzine and trihexyphenidyl represent compounds that possibly have both anticholinergic and NMDA antagonistic properties. PMID- 8515904 TI - Involvement of cytokines in acute neurodegeneration in the CNS. AB - Cytokines, (particularly interleukins and growth factors) are synthesised in the brain, and induced by brain damage. Interleukin-I appears to directly mediate ischaemic and excitotoxic brain damage, whereas growth factors (e.g., bFGF, NGF), and the phospholipid binding protein lipocortin-1 exhibit neuroprotective actions. Central administration of recombinant interleukin-1 receptor antagonist markedly attenuates damage induced by focal cerebral ischaemia, or pharmacological activation of NMDA receptors in the rat brain. The mechanisms of action of these cytokines on neurodegeneration are unknown, but indirect evidence has implicated corticotropin releasing factor, arachidonic acid, and nitric oxide. In vitro effects of interleukin-1, growth factors, and lipocortin-1 have been reported on intracellular calcium homeostasis, which is critically important in neurodegeneration. Pharmacological modulation of the expression and/or actions of cytokines in the brain may be of considerable therapeutic benefit in the treatment of acute neurodegeneration. PMID- 8515905 TI - Silent ischemia: a hypothetical mechanism. AB - Ischemia of visceral organs, especially the heart, is often a painful and potentially life-threatening condition. However, in at least 75% of all cases myocardial ischemia may be "silent" (i.e., without pain or sensation). Yet, the mechanisms responsible for silent ischemia are not well understood. As such, many different theories have been advanced to explain silent ischemia; however, none have been able to adequately explain all of the experimental and clinical findings. This paper proposes a hypothetical mechanism that may help to understand mechanisms of silent ischemia. PMID- 8515906 TI - Extreme immaturity: outcome of 568 pregnancies of 23-26 weeks' gestation. AB - OBJECTIVE: To provide guidelines to the perinatologist regarding extremely premature infants based on the experience of the University of Toronto Newborn Service (two high-risk perinatal units and one outborn neonatal intensive care unit), with a catchment area of 60,000 deliveries annually. METHODS: The study included all births or admissions in the Newborn Service from January 1, 1982 to June 30, 1987 with gestational age determined by the best obstetric estimate of gestational age, ranging from 23-26 completed weeks. The obstetric records were reviewed and the surviving infants followed prospectively for a minimum of 2 years after delivery. RESULTS: Analysis of the neonatal and 2-year follow-up data on 568 infants born between 23-26 weeks' gestation revealed a 39% mortality rate, which increased with decreasing gestation. The highest mortality rates occurred following complicated pregnancies, including fetal growth restriction. Intact survival increased with increasing gestational age, from 11% at 23 weeks to 50% at 26 weeks. There was a marked improvement in both mortality and morbidity by 25 completed weeks. CONCLUSIONS: The results suggest that an aggressive approach before 24 completed weeks' gestation is not warranted. From a total of 60,000 live births per year, only one child born at 23 weeks' gestation and three at 24 weeks were free of major handicap at 2 years. PMID- 8515907 TI - Timing of reproductive life stages. AB - OBJECTIVE: To identify typical ages at which women pass through reproductive transitions and to ascertain whether they differ by poverty status, race, and ethnicity, and from men's transition ages. METHODS: Using the 1982 and 1988 National Surveys of Family Growth, the 1988 National Survey of Young Men, and the March 1988 Current Population Survey, the timing of transitions between stages was measured by the ages at which respondents had passed specific milestones. RESULTS: By age 17.4, half of the young women surveyed and by age 16.6, half of the young men had had intercourse. The length of time the typical woman spent being sexually active before marriage increased by more than 1.5 years, to nearly 7 years, between 1982 and 1988. Half of all women surveyed had become mothers by age 26 and by age 30 half intended to have no more children; half were sterile for contraceptive or noncontraceptive reasons by age 35.7. Non-Hispanic white and higher-income women typically married before their first birth, whereas half of black women became mothers almost 6 years before a similar proportion had married. Lower-income and Hispanic women demonstrated smaller but similar gaps. CONCLUSIONS: Differences among subgroups and the broad age ranges at which women move between stages highlight the importance of focusing service delivery and education according to the stage of a woman's reproductive life, not just her age. Current patterns of timing are not prescriptive, but provide a framework for directing efforts to provide women and men with needed information and services and to assess the possible effects. PMID- 8515908 TI - Isolated congenital heart block: fetal and infant outcome and familial incidence of heart block. AB - OBJECTIVE: To determine the 1-year outcome of infants with isolated congenital heart block, the risk of fetal loss in mothers of affected infants, and the risk of recurrence of congenital heart block. METHODS: The outcomes of 34 infants with isolated congenital heart block and of the 109 pregnancies in the 32 mothers of these infants were analyzed retrospectively. A control group consisted of 170 pregnancies in 64 women individually matched for age, parity, and socioeconomic status. RESULTS: Five (15%) of the 34 infants with isolated congenital heart block died before 1 year of age. The relative risk for fetal loss in mothers of affected children, after the exclusion of a mother with 16 spontaneous abortions, was 1.9 (95% confidence interval 0.9-3.8; P = .094). The prevalence of congenital heart block in all siblings of children with congenital heart block was 4% (two of 45). The risk of having a child with congenital heart block after a previous birth of an affected child was 8% (two of 26). CONCLUSIONS: Infant mortality in isolated congenital heart block is considerable, and mothers of affected children tend to have an increased risk of fetal loss. However, the risk of recurrence of congenital heart block is low. PMID- 8515909 TI - Oral contraceptive risk assessment: a survey of 247 educated women. AB - OBJECTIVE: To determine womens' beliefs regarding the risks and health benefits of oral contraceptives (OCs). METHODS: Between April 26 and June 7, 1991, 247 women completed a self-administered questionnaire at the Yale University Health Services evaluating their perceptions of the risks and benefits of OC agents. RESULTS: The mean age of the study population was 30.2 years (range 16-68), and more than 90% of the study group had at least 1 year of college education. Forty nine percent of the study group believed there are substantial risks to OC use. Between 80-95% of women were unaware of the following health benefits of OCs: decreased risks of endometrial cancer, ovarian cancer, pelvic inflammatory disease, ectopic pregnancy, anemia, and benign breast disease. CONCLUSIONS: Perceptions of the risks of OCs are exaggerated and there is a clear knowledge deficit with regard to their health benefits. Increased educational efforts by health care providers should emphasize the health benefits of OCs and attempt to dispel the common misconceptions. PMID- 8515910 TI - Long-term effect of tubal sterilization on menstrual indices and pelvic pain. AB - OBJECTIVE: To evaluate the long-term effect of tubal sterilization on menstrual indices and pelvic pain. METHODS: Five hundred women undergoing sterilization were interviewed before sterilization, 6-10 months after surgery, and 3-4.5 years later. Four hundred sixty-six non-sterilized comparison women were interviewed in parallel. The study population consisted of low-income, ethnically and regionally diverse women from three participating institutions. RESULTS: When women who were taking oral contraceptives were excluded, no long-term differences was found between sterilized and nonsterilized women in terms of menstrual cycles, bleeding between periods, prolonged or heavy flow, dysmenorrhea, or noncyclic pelvic pain. Hysterectomy was uncommon (3.2%), but statistically more prevalent among sterilized women (4.55%) than nonsterilized women (2.17%) (P = .019). CONCLUSIONS: Tubal sterilization has no long-term effect on menstrual indices or pelvic pain. An increase in severe dysmenorrhea, which emerged as a disturbing but nonsignificant trend at 6-10 months, did not progress over the next 3-4.5 years. Reasons for an increased rate of hysterectomy are not clear, but may be related to a lower threshold for choosing hysterectomy as a treatment option once a woman has been sterilized. PMID- 8515911 TI - Use of infertility services in the United States. AB - OBJECTIVE: To examine the characteristics of women in the 1988 National Survey of Family Growth who reported having obtained medical services for impaired fecundity. METHODS: From a national sample of 8450 women between the ages of 15 44, drawn from the civilian, noninstitutionalized population of the entire United States in 1988, we estimated the use of infertility services in the United States. Multivariate statistical modeling was used to identify the characteristics associated with use of infertility services among the 770 women who reported impaired fecundity in this survey. RESULTS: Of all women with impaired fecundity, 43% had obtained some form of infertility service and 24% had obtained specialized infertility treatment--ovulation drugs, treatment of fallopian tubes, artificial insemination, or in vitro fertilization. Older, white, married women of higher socioeconomic status were most likely to have obtained specialized services, and a history of endometriosis was also strongly associated with having received such services. CONCLUSION: Most women with impaired fecundity had not obtained infertility services. Use of specialized services was strongly associated with certain sociodemographic variables or a history of endometriosis. PMID- 8515912 TI - Variation in spontaneous abortion rate relates to the indication for therapeutic donor insemination. AB - OBJECTIVE: To evaluate the relationship between indications for donor insemination and the rate of spontaneous abortion of these pregnancies. METHODS: All therapeutic donor insemination pregnancies from our clinic over a 15-year period were categorized according to the indications for insemination, recipient's age, cycle of conception, use of ovulation-inducing agents, use of fresh or frozen semen, and pregnancy outcome. Spontaneous abortion rates were compared between groups segregated according to the indication for donor insemination; differences in maternal age were taken into account. Statistical evaluation was done using chi 2 analysis. RESULTS: Women whose partners produced some sperm in their ejaculates had a spontaneous abortion rate of 21.8%, as compared to 15.4% for women whose partners were azoospermic (P < .05). When couples with oligospermia were segregated by degree of oligospermia, those with counts greater than 2 x 10(6)/mL had an abortion rate of 26.2%, as compared to 11.7% in those with counts less than 1 x 10(6)/mL (P < .025). CONCLUSIONS: The indication for performing therapeutic donor insemination has an influence on the resultant spontaneous abortion rate. Several possible reasons for this relationship may exist, but more data will be needed for verification. A better understanding of the influences that the indication for donor insemination has upon the outcome will facilitate more accurate counseling of candidate couples. PMID- 8515913 TI - Predicting recurring miscarriage: what is important? AB - OBJECTIVE: To audit the Miscarriage Clinic in Liverpool and to categorize women into those at low and high risk of a subsequent pregnancy loss. METHODS: Over 4 years (1989-1992), 203 consecutive couples attended the Miscarriage Clinic in Liverpool. A data base was designed and a mathematical model formulated that described the data base. RESULTS: A successful pregnancy outcome was most likely in the presence of the following features: menstrual regularity, fewer than four previous miscarriages, maternal age of less than 30 years, absence of antiphospholipid antibodies, and a previous live birth. Oligomenorrhea was a considerably more significant feature than any other in predicting a subsequent miscarriage. These high-risk oligomenorrheic women were found to have low luteal phase estradiol levels, but normal luteal phase progesterone profiles and normal LH profiles throughout the menstrual cycle. CONCLUSIONS: Women suffering from recurring miscarriage can be placed into differing risk categories. Women with a good prognosis require counseling alone. Women at high risk of a subsequent miscarriage had oligomenorrhea and an isolated deficiency of estradiol in the luteal phase of the menstrual cycle. PMID- 8515914 TI - Second-look laparotomy in stage I ovarian cancer following comprehensive surgical staging. AB - OBJECTIVE: To evaluate the role of second-look laparotomy in patients with comprehensively staged stage I epithelial ovarian cancer. METHODS: We reviewed the medical records and obtained long-term follow-up on 54 stage I patients who had second-look laparotomies following complete surgical staging and chemotherapy. RESULTS: The distribution by stage was as follows: stage IA 18 (33%), stage IB two (4%), and stage IC 34 (63%). Eighteen patients (33%) had endometrioid tumors, 12 (22%) clear cell, 13 (24%) mucinous, eight (15%) serous, and three (6%) undifferentiated. Forty-four patients (82%) had grade 2 or 3 tumors. Thirty-eight (70%) were treated with platinum-based regimens and 16 (30%) received non-platinum regimens. At second-look laparotomy, tumor was identified in three women (5.5%). Stage, cell type, and grade did not predict the second look laparotomy result, although no patient with a grade 1 tumor had a positive second-look laparotomy. With a mean follow-up of 48 months from second-look laparotomy, 11 women (22%) have had recurrences following negative second looks. Tumor grade was a strong predictor of recurrence following negative second-look laparotomy (P < .0001), with the risk of recurrence being 0% for grades 1 and 2 and 52% for grade 3. Substage, cell type, and chemotherapy type and duration did not predict recurrence. CONCLUSIONS: The likelihood of a positive second-look laparotomy is about 5% in well-staged stage I ovarian cancer. Patients with stage I, grade 3 tumors have a risk of recurrence of approximately 50% following negative second-look laparotomy. PMID- 8515915 TI - Platinum-based chemotherapy of high-risk stage I epithelial ovarian cancer following comprehensive surgical staging. AB - OBJECTIVE: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. METHODS: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum-based chemotherapy following comprehensive surgical staging. Clinicopathologic correlations were performed using disease-free survival as the end point. RESULTS: The mean patient age was 47 years. The distribution by stage was IA in 19 (31%), IB in four (6%), and IC in 39 (63%). Eighty percent of the patients had grade 2 or 3 tumors. The distribution by cell type was as follows: clear-cell 22 (35%), endometrioid 15 (24%), mucinous 11 (18%), serous eight (13%), and undifferentiated six (10%). The patients underwent an average of six cycles of platinum-based therapy. With a median follow-up of 40 months among survivors, 15 patients (24%) have relapsed, at a median interval of 22 months from diagnosis. Relapses occurred primarily in the peritoneal cavity and retroperitoneal lymph nodes. No patient has been rendered free of disease after relapse. Patients with grade 3 tumors had an increased risk of relapse as compared to those with grade 1 or 2 tumors (46 versus 8%; P = .002). Patients with clear-cell tumors had a higher risk of relapse than those with other cell types (41 versus 15%; P = .05). There was no statistically significant relationship between risk of recurrence and substage. None of 11 patients with stage IA, grade 2 disease had recurrence. Actuarial 5 year disease-free survival for the entire group of 62 patients was 73%. CONCLUSION: Platinum-based chemotherapy for high-risk stage I ovarian cancer does not appear to improve survival over that previously reported with non-platinum regimens. PMID- 8515916 TI - The effect of pregnancy weight gain on later obesity. AB - OBJECTIVE: To determine whether weight increases permanently as a result of pregnancy and to explore the determinants of postpartum weight retention. DATA SOURCES: Articles from the literature on obesity, parity, and gestational and postpartum weight changes were identified through a literature search. METHODS OF STUDY SELECTION: Studies from the last decade that examined weight changes related to pregnancy or parity in developed countries were selected if they provided adequate information to allow useful comparisons to other studies. DATA EXTRACTION AND SYNTHESIS: Average gestational and postpartum weight changes and their range of variation were noted. Studies emphasizing information related to weight change were used to identify alternative explanations for weight changes often credited to pregnancy. Explanations consistent with data from all of the different kinds of studies were developed by synthesis of the varied reports. CONCLUSIONS: Aging is a major determinant of weight increases associated with parity in cross-sectional studies. Average weight increments are generally less than 1.5 kg (3 lb) during a single reproductive cycle (before pregnancy to 1 year postpartum), but obese women tend to have larger weight changes (both increases and decreases) than lower-weight women. Under-reporting of pre-pregnancy weight, particularly by overweight women, probably contributes to overestimation of weight gain during pregnancy and estimated retained weight. A small number of women increase weight greatly during a reproductive cycle. The studies do not prove that this is the result of the pregnancy per se. Some women gain weight postpartum, suggesting that life-style factors can be significant determinants of weight gain during a reproductive cycle. Preventive efforts targeted to the postpartum visit could be useful. PMID- 8515917 TI - A prospective study of postpartum candy gift net weight: correlation with birth weight. AB - This study assesses the widely held but previously untested hypothesis that the net weight of postpartum candy gifts from parents to delivery suite and postnatal ward staff is proportional to their neonates' birth weight. Midwives at Musgrove Park Hospital in Taunton, Somerset, United Kingdom were requested to record the details of all candy gifts received over a 6-month period in 1992. Only 39 candy gifts from 1491 deliveries were documented, with a mean net weight of 416 g. The coefficient of correlation between candy weight and birth weight was 0.1477 (P = .2). The basis for the association is multifactorial. Socioeconomic and prematurity-related factors were responsible for poor candy giving following low birth weight deliveries. In contrast, factors related to the etiology and psychology of obesity and diabetes were implicated in generous candy giving by the high birth weight population. PMID- 8515918 TI - Comparison of problem-based and traditional education on student performance in the obstetrics and gynecology clerkship. AB - OBJECTIVE: To evaluate the hypothesis that students trained in problem-based learning during basic sciences will have an advantage over traditionally trained students during clinical activities because of greater experience in patient care settings. METHODS: A retrospective study encompassing the academic years 1985 1990 compared students' clinical performance during an obstetrics and gynecology third-year clerkship based on the method of basic science education (problem based 78, traditional 228). RESULTS: No statistical difference could be demonstrated in student performance based on the basic science educational method and controlling for the timing of rotation. CONCLUSIONS: Participation in a problem-based curriculum does not affect students' performance on standardized objective examinations within the clinical curriculum. Using current evaluation tools, there is no measurable difference in clinical evaluations between basic science education by traditional versus problem-based learning methods. PMID- 8515919 TI - Immediate postpartum curettage: accelerated recovery from severe preeclampsia. PMID- 8515920 TI - Delayed postpartum hemorrhage: a morphologic study of causes and their relation to other pregnancy disorders. AB - OBJECTIVES: To ascertain the various causes of delayed postpartum hemorrhage and to test whether subinvolution of the placental bed is associated with other pregnancy disorders for which defective maternal-fetal interaction has been implicated pathogenetically. METHODS: In a group of women presenting with postpartum hemorrhage following singleton pregnancies, tissue that had been submitted for histopathologic examination was reviewed morphologically to delineate the various causes of delayed postpartum hemorrhage. The stratified groups were analyzed for relationship to preeclampsia, fetal growth retardation (FGR), spontaneous abortion, placenta accreta, and retained placental fragments in previous pregnancies. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each association. RESULTS: One hundred sixty-nine cases were identified. Tissue obtained at curettage or, rarely, at hysterectomy could be categorized into seven pathologic groups: involution of the placental bed, subinvolution of the placental bed, retained placental fragments, endometritis, normal endometrium, normal decidua, or nondiagnostic tissue. Hyalinized fragments of uteroplacental (spiral) arteries that were either collapsed or completely thrombosed were seen in involution of the placental bed. Subinvolution of the placental bed was characterized by widely distended and patent residua of uteroplacental arteries with only partial occlusion by thrombosis. Women with retained placental fragments (OR 3.93, 95% CI 1.51-10.47), but not women with an involuted placental bed (OR 2.40, 95% CI 0.68-8.54) or subinvolution of the placental bed (OR 1.52, 95% CI 0.51-4.57), had increased incidences of preeclampsia, FGR, spontaneous abortion, or retained placenta in previous pregnancies when compared to women with endometritis, endometrium only, decidua only, or nondiagnostic tissue. CONCLUSION: Retained placental fragments, reflecting placenta accreta, and subinvolution of the placental bed are important causes of delayed postpartum hemorrhage. The former is associated with an increased incidence, in prior pregnancies, of pregnancy complications that probably reflect aberrant maternal-trophoblastic interaction. PMID- 8515921 TI - Unexpected stimulatory effect of progesterone on human myometrial contractile activity in vitro. AB - OBJECTIVE: To investigate the effects of continuous exposure of progesterone on contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsy specimens were obtained from 14 term pregnant women undergoing elective cesarean. The specimens were immediately immersed in Hepes buffer and buffer containing 0.33, 4.1, and 70 micrograms/mL progesterone. Muscle biopsies were dissected along the bundles of smooth muscle under stereomicroscope. These myometrial strips were mounted in tissue baths and superfused with Hepes buffer and buffer containing different concentrations of progesterone. RESULTS: The progesterone concentration of 0.33 microgram/mL had no significant effect on myometrial contractile activity. The concentrations of 4.1 and 70 micrograms/mL increased the frequency of contractions (P < .01 for each) and tonus (P < .01 for each), decreased the activity area of contractions (P < .01 for each), and delayed the onset of contractions (P < .01 and P < .05, respectively). CONCLUSION: When the myometrium is not deprived of progesterone, this hormone may have excitatory effects on the frequency of contractions and tonus of the lower uterine segment of term human myometrium. PMID- 8515922 TI - Production of fibrogenic cytokines by interleukin-2-treated peripheral blood leukocytes: expression of transforming growth factor-beta and platelet-derived growth factor B chain genes. AB - OBJECTIVE: To assess the production of fibrogenic cytokines by interleukin-2 (IL 2)-stimulated peripheral blood leukocytes and to examine their ability to stimulate the production of connective tissue. METHODS: Culture medium from human peripheral blood leukocytes incubated with or without IL-2 was tested for induction of fibroblast proliferation, collagen synthesis, and expression of cytokine genes. RESULTS: Supernatants from IL-2-treated peripheral blood leukocytes induced six times more fibroblast proliferation than medium from leukocytes cultured without IL-2. The expression of type I procollagen and fibronectin messenger RNAs was increased in human fibroblasts in response to leukocyte supernatants. Unstimulated leukocytes expressed minimal levels of transforming growth factor-beta or platelet-derived growth factor B chain messenger RNAs, but could be greatly enhanced by IL-2 treatment. CONCLUSION: Mediators that induce connective tissue production are secreted by IL-2-treated peripheral blood leukocytes. These cytokines may be responsible, in part, for the stimulation of abdominal adhesions in patients receiving intraperitoneal immunotherapy. PMID- 8515924 TI - Nuchal thickening or cystic hygromas in first- and early second-trimester fetuses: prognosis and outcome. AB - OBJECTIVE: To elucidate the relationship between nuchal abnormality, karyotype, and prognosis in fetuses with nuchal thickening or cystic hygroma observed between 10-15 weeks' gestation. METHODS: We reviewed all cases of fetal nuchal thickening (4 mm or greater) in 10-15-week fetuses over a 5-year period. Generalized hydrops and the presence of other anomalies were noted prospectively. We retrospectively measured the nuchal area and determined whether septations were present. Data consisted of karyotype, pathologic studies, and clinical follow-up of live-born infants. RESULTS: Of 100 consecutive fetuses, 29 were excluded because of pregnancy termination without karyotype or pathologic information. Of the remaining 71 fetuses, 63 had karyotyping. Abnormal karyotypes were found in 31 of 37 hydropic fetuses but in only 12 of 26 nonhydropic fetuses (P < .05). Fetuses with Turner syndrome had larger cystic hygromas than those with trisomy 18, trisomy 21, or normal karyotype (P < .05). There were ten normal live-born infants, none of whom was hydropic at the time of initial diagnosis and all of whom demonstrated spontaneous resolution of the nuchal thickening on subsequent sonograms. CONCLUSIONS: Fetuses with nuchal thickening or cystic hygromas demonstrated by ultrasound should have their karyotype determined. If the karyotype is normal and there are no hydrops or septations, the prognosis is good. PMID- 8515923 TI - Perinatal lethal conditions: the effect of diagnosis on decision making. AB - OBJECTIVE: To identify factors influencing pregnancy management decisions following identification of a perinatal lethal condition. METHODS: One hundred thirty pregnancies with perinatal lethal conditions diagnosed before 24 weeks' gestation were examined. Information collected included demographic data, estimated gestational age at presentation, referral indication, nature of the defect, and performance of autopsy. RESULTS: Eighty-seven families elected to abort affected pregnancies and 43 elected to continue. Demographic factors did not influence decision making, nor did gestational age at diagnosis or referral indication. When comparing the diagnosis of one lethal condition with diagnoses of all other lethal conditions, pregnancies with a central nervous system defect or severe urinary tract defect were more often aborted; those with unexplained severe oligohydramnios and twin pregnancies in which at least one twin was affected were more often continued. Autopsy was obtained much more often in pregnancies that were aborted than in those that were continued. CONCLUSION: The type of defect correlates well with the pregnancy management decision. It is important to consider the type of malformation, certainty of the diagnosis, and level of medical understanding when counseling patients after the diagnosis of a lethal fetal defect. Because many patients will continue pregnancies diagnosed with a perinatal lethal condition, the physician should convey understanding and acceptance of a decision not to abort such a pregnancy. The importance of follow up testing, including autopsy when appropriate, should be stated clearly. PMID- 8515925 TI - Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling. AB - OBJECTIVE: To evaluate prospectively the relative risks and accuracy of first trimester chorionic villus sampling (CVS) and second-trimester amniocentesis in the genetic evaluation of twin gestations. METHODS: Between March 1984 and August 1990, patients presenting for prenatal diagnosis of a twin gestation of less than 12 weeks were offered sampling by either first-trimester CVS or amniocentesis at 16-18 weeks' gestation. Selection was based solely on patient preference and was obtained before ultrasound identification of placental position. Women presenting beyond 12 weeks' gestation were sampled by amniocentesis. Clinical and laboratory outcomes were evaluated. RESULTS: Eighty-one women had amniocentesis (nine of whom also had CVS), and 161 women had CVS. All fetuses in both groups were successfully sampled and karyotyped; 85.3% of the amniocentesis patients and 75.8% of the CVS patients were sampled in two or fewer passes (P = not significant). There were three cases of twin-twin villus contamination following CVS; one of these led to incorrect gender assignment because of erroneous laboratory interpretation. Loss of the entire pregnancy from the time of sampling until the 28th week of gestation followed amniocentesis in 2.9% of the cass and CVS in 3.2%. The total fetal loss rates were 9.3% for amniocentesis and 4.9% for CVS (P = not significant). When pregnancies having mosaic or abnormal karyotype results are excluded, the total amniocentesis loss rate remained 9.3% and the CVS loss rate became 3.9% (P < .05). CONCLUSION: In the hands of experienced operators, CVS is at least as safe and effective as amniocentesis for the prenatal diagnosis of twin gestations. PMID- 8515926 TI - A report of 131 cases of multifetal pregnancy reduction. AB - OBJECTIVE: To evaluate multifetal pregnancy reduction as a treatment for patients seeking to reduce the risks of multiple gestation. METHODS: One hundred thirty one women had transabdominal multifetal pregnancy reduction performed by a single practitioner; 103 have delivered. RESULTS: Multifetal pregnancy reduction was associated with a 7% pregnancy loss rate and no losses within the first 4 weeks after the procedure. The mean gestational age at delivery overall was 35.5 weeks. The mean gestational age at delivery for singletons was 37.5 weeks, for twins 35.5 weeks, and for triplets 35 weeks. The incidence of maternal and fetal complications was no more than that previously reported for nonreduced multiple gestations. CONCLUSIONS: Multifetal pregnancy reduction is a safe option for patients who desire to reduce the risks of multiple gestation. The ultimate successful outcome of reduced pregnancies may be enhanced by extensive experience with the procedure. PMID- 8515927 TI - Efficacy of transabdominal multifetal pregnancy reduction: collaborative experience among the world's largest centers. AB - OBJECTIVE: To evaluate the safety and efficacy of transabdominal multifetal pregnancy reduction (MFPR) in the management of iatrogenic and spontaneous multifetal pregnancies. METHODS: Data were combined from 463 completed pregnancies that underwent MFPR at major worldwide centers. RESULTS: Multifetal pregnancy reduction was performed with a 100% technical success rate (there were no failed procedures); 83.8% had delivery of potentially viable fetuses (defined as 24 weeks' gestation or later), and 83.5% of these viable pregnancies delivered at 33 weeks or later. The risk of fetal loss was 3.9% at 2 weeks or less post procedure, 4.6% at 4 weeks or less, and 16.2% at less than 24 weeks of gestation. Gestational age at delivery varied principally with the number of fetuses remaining, with 7.1% delivering prematurely at less than 28 weeks, and 9.4% at 29 32 weeks. The incidence of obstetric and medical complications appeared to be unaffected, and there was no increase in congenital malformations. CONCLUSIONS: Multifetal pregnancy reduction is an efficient and safe way of improving outcome in multifetal pregnancies, unambiguously for quadruplets or more, and arguably for triplets. However, particularly at higher starting numbers, there are still suboptimal outcomes. We cannot answer the question of whether MFPR should be offered to women with triplets or twins. The only major risk appears to be fetal loss per se, and because the procedure itself does not damage the survivors, parental autonomy should be given a higher priority in the decision process than previously. However, to obviate the need for this procedure, infertility specialists must continue to be vigilant in the use of fertility drugs. PMID- 8515928 TI - Effect of nicardipine on the reversal of magnesium toxicity by calcium gluconate in nonpregnant rabbits. AB - OBJECTIVE: To determine whether nicardipine, a dihydropyridine, inhibits the ability of calcium gluconate to reverse magnesium-induced toxicity. METHODS: The reversal of magnesium-induced neuromuscular blockade of skeletal muscle in the presence of nicardipine was assessed using a nerve stimulator. Nicardipine (12 mg) or an equivalent volume of saline was administered intramuscularly to 19 nonpregnant rabbits in a randomized, blinded manner. Magnesium sulfate, 800 mg, was then infused intravenously in all animals, an amount sufficient to cause toxicity as measured by depression of skeletal muscle twitch and by average serum levels of 10.4 mEq/L. Calcium gluconate (300 mg) was then infused in all animals, and reversal of neuromuscular blockade was measured using the nerve stimulator to compare the saline- and nicardipine-treated groups. RESULTS: Administration of calcium gluconate was equally effective in reversing magnesium-induced toxicity in both the control and test groups. CONCLUSION: Nicardipine does not block the ability of calcium gluconate to reverse magnesium-induced neuromuscular blockade. PMID- 8515929 TI - Plasma brain natriuretic peptide level in pregnant women with pregnancy-induced hypertension. AB - OBJECTIVE: To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension. METHODS: We determined the plasma levels of brain and atrial natriuretic peptides in a cross sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension. RESULTS: During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P < .05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P < .001). CONCLUSION: The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation. PMID- 8515930 TI - Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging. AB - OBJECTIVE: To assess the value of the early diastolic notch and color Doppler imaging of the uterine arteries at 24 weeks' gestation in a two-stage Doppler screening test for preeclampsia. METHODS: Two thousand fifty-eight unselected women had an initial screening study with continuous-wave Doppler at 18-22 weeks' gestation. Color Doppler imaging was used at 24 weeks' gestation to examine both uterine arteries in 273 women with initial abnormal results (high resistance index or diastolic notch). RESULTS: Three hundred twenty-nine women (16%) had abnormal flow velocity waveforms at the first stage and 104 (5.1%) at the second stage of Doppler screening. The presence of an early diastolic notch in the flow velocity waveform was significantly better than a high resistance index at predicting preeclampsia at both 20 and 24 weeks; the relative risk of developing significant preeclampsia for a woman with a persistent notch at 24 weeks was increased 68-fold. All women delivered before 34 weeks because of severe preeclampsia had abnormal waveforms at both stages of screening. CONCLUSION: An early diastolic notch in the flow velocity waveform is a better predictor of preeclampsia than are conventional impedance indices. Preeclampsia can be predicted effectively by two-stage Doppler screening. PMID- 8515931 TI - Electronic fetal monitoring in the United States in the 1980s. AB - OBJECTIVE: To measure the frequency with which electronic fetal monitoring was used for childbirth in United States hospitals in the 1980s and to examine variation in use according to risk factors at labor onset. METHODS: Two data sets from the National Center for Health Statistics (the 1980 National Natality Survey and the 1988 National Maternal and Infant Health Survey) were used to generate proportional frequencies for electronic fetal monitoring use. These data files are based on representative samples of live births (9941 and 9953, respectively) drawn by probability methods from the entire country during a calendar year. Consistency in the sampling methods and questionnaire procedures, and use of sampling weights, permitted national estimates to be generated. RESULTS: Use of electronic fetal monitoring increased from 44.6% of live births in 1980 to 62.2% in 1988. In both time periods, low-risk women received monitoring more frequently than did women with risk indicators. Use grew by 64% in low-risk women (from 46.5% in 1980 to 76.3% in 1988) but only by 32% in women with risk conditions at labor onset (from 42.6% in 1980 to 56.2% in 1988). CONCLUSIONS: Use of electronic fetal monitoring increased during the 1980s, disproportionately so for low-risk women. This trend raises questions about the efficacy of monitoring for improving pregnancy outcomes. PMID- 8515932 TI - Placental previa in relation to induced and spontaneous abortion: a population based study. AB - OBJECTIVE: To evaluate the impact of induced abortion and spontaneous abortion on the occurrence of placenta previa in later pregnancies. METHODS: A population based, case-control study was conducted using 1984-1987 Washington state birth certificate data. The study population included 486 white women with a pregnancy complicated by placenta previa and 1598 randomly selected controls without placenta previa. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: After adjustment for confounding variables, the odds ratio in association with one or more induced abortions was 1.28 (95% CI 1.00-1.63). For one or more spontaneous abortions, the odds ratio was 1.30 (95% CI 1.01-1.66). CONCLUSIONS: Women who report one or more induced or spontaneous abortions are 30% more likely to have a subsequent pregnancy complicated by placenta previa than women without such a history. The results should not be generalized to areas where suction curettage is not the preferred method of induced abortion. PMID- 8515933 TI - Community-wide estimation of illicit drug use in delivering women: prevalence, demographics, and associated risk factors. AB - OBJECTIVE: To determine the community-wide prevalence of illicit drug use in delivering women and to compare rates in women delivering in an urban center serving the medically indigent with those delivering in private hospitals. METHODS: Over 6 weeks, 1062 urine samples were obtained anonymously from women presenting for delivery in seven hospitals in the Jacksonville, Florida area. All urine samples were analyzed blindly for illicit drugs using fluorescent polarized immunoassay. RESULTS: The percentage of women with positive urine toxicology was 7.1%. Positive results were more frequent in the public hospital population (12.7%) than the private hospital population (3.9%). The prevalence of cocaine use was 2.1% and marijuana 5.3%. Urine positivity was similar in black and white women, with cocaine metabolites more prevalent in black women and cannabinoids more common in white women. Women with positive screens for cocaine were more likely to use tobacco and alcohol, admit to substance abuse, and receive limited prenatal care. Women with positive screens for marijuana were difficult to differentiate from the urine-toxicology-negative group. CONCLUSIONS: Urine samples positive for illicit drugs were significantly more common in women delivering in an urban center serving the indigent population than in those delivering in private hospitals. Based on associated factors, cocaine users fit a more indentifiable profile than marijuana users. The overall incidence of positive urine toxicology was no different in black and white pregnant women, but the more frequent finding of cocaine metabolites in black women may lead to biased over-reporting of substance abuse in this population. PMID- 8515935 TI - Tuberculosis' comeback alarms public healthcare professionals. 'Excess cases' prompts CDC and other groups to recommend precautions for workers. PMID- 8515934 TI - Ultrasound diagnosis of uterine myomas and complications in pregnancy. AB - OBJECTIVE: To evaluate myomas for ultrasound-documented size, location, position, and relation to the placenta, and to relate these findings to complications during pregnancy, at delivery, and in the puerperium. METHODS: Among 12,708 pregnant patients who had ultrasound scans, 492 had uterine myomas. Single myomas were found in 88% of cases and multiple myomas in 12%. The myomas were evaluated for size, number, position, location, relationship to the placenta, and echogenic structure, and the outcome of pregnancy was compared to that of patients in the control group. RESULTS: A statistically significant increased incidence of threatened abortion, threatened preterm delivery, abruptio placentae, and pelvic pain was observed in patients with uterine myomas (P < .001). Abruptio placentae was particularly evident in women with myoma volumes greater than 200 cm3, submucosal location, or superimposition of the placenta. Pelvic pain was related to myoma volume greater than 200 cm3 and ultrasound findings of heterogeneous echo patterns and cystic areas. Mode of delivery, abortion, preterm birth, premature rupture of membranes, and fetal growth did not seem to be affected by the presence of myomas. Thirty-two women with uterine myomas were managed surgically. Thirteen underwent myomectomy during pregnancy. Of these, eight delivered at term and five delivered preterm after the 32nd week of gestation. None of the deliveries were associated with neonatal death. The other 19 patients had surgery at delivery. Nine myomectomies were performed at cesarean delivery. Of these, three were complicated by severe hemorrhage necessitating hysterectomy. Another nine hysterectomies were performed during cesarean and one after vaginal delivery. CONCLUSIONS: In addition to myoma size, the ultrasound evaluation of pregnant women with myomas should include position, location, relationship to the placenta, and echogenic structure. These ultrasound findings make it possible to identify women at risk for myoma-related complications and could be useful in managing the pregnancy. PMID- 8515937 TI - Supply line--respiratory protection. PMID- 8515936 TI - Respiratory program develops training, fit-testing routines. Respiratory equipment minimizes exposure to potentially hazardous airborne contaminants. PMID- 8515938 TI - Perils in the fields. PMID- 8515939 TI - When pest control gets out of control. PMID- 8515940 TI - Review of system designs employs ergonomics prior to work injuries. CTDs do not need to be the result of trial-and-error processes with new or simpler equipment. AB - The six stages of complex man/machine systems design can and should be applied to simpler systems as well. This process ensures that operator performance requirements are carefully considered and that operators will not be overloaded. When ergonomic considerations are ignored, cumulative trauma disorders among operators often occur after weeks, months or years of system use. Many problems can be avoided with little or no additional cost if ergonomics is considered during the design or equipment selection phase of new systems. For existing systems, an ergonomics review can determine the necessary interface enhancements or function re-allocations that will resolve problems, and reduce the likelihood of injury. PMID- 8515941 TI - Hearing protection plans require proper ear plug selection, usage. Train workers on noise hazards and motivate them to wear hearing protectors. PMID- 8515942 TI - An open letter to Hillary Rodham Clinton. PMID- 8515943 TI - An ophthalmologist's health-care proposal. PMID- 8515944 TI - Subconjunctival THC:YAG laser sclerostomy for the treatment of glaucoma: preliminary data. AB - A subconjunctival thermal sclerostomy was performed using the recently developed THC:YAG laser in 33 eyes with a variety of glaucomas in which, in most cases, neither medical therapy nor previous procedures had been successful in controlling intraocular pressure (IOP). The mean preoperative IOP was 27.5 +/- 7.5 mm Hg with maximum medication. The laser procedure was quick and easy, with minimal manipulation of tissues; complications were clinically insignificant. The day after the operation, 23 eyes had an IOP less than 18 mm Hg; in the other 10, it was unchanged. In most of the eyes, an obvious filtering bleb developed at the site of the sclerostomy. The internal opening of the sclerostomy was visible on gonioscopy, except in five cases, in which it was plugged by a fold of the iris root. One year after the operation, IOP was controlled in three eyes without medication and in 18 with medication. IOP remained uncontrolled in the remaining 12 eyes. PMID- 8515945 TI - The efficacy of cw Nd:YAG laser trabeculoplasty. AB - The long-term (mean follow up, 51 weeks) efficacy of cw Nd:YAG laser trabeculoplasty in reducing intraocular pressure (IOP) was studied in 106 eyes of 75 patients. Fifty patients (73 eyes) of this group had primary open-angle glaucoma; 11 (17), mixed glaucoma; 10 (12), pseudoexfoliation syndrome; and 4 (4), secondary glaucoma of varied etiology. Fifty laser impacts were delivered over 180 degrees of the circumference of the chamber angle with an Nd:YAG laser working in the cw mode (spot diameter, 100 microns; exposure duration, from 200 to 300 milliseconds; constant power level, 9 W, resulting in 1.8 to 2.7 J/pulse and a total energy dose/session of 90 to 135 J). In a few cases, an exposure duration of 400 milliseconds was used, corresponding to a pulse energy of 3.6 J/pulse and a total energy dose/session of 180 J. Success was defined as a reduction in IOP to 22 mm Hg or less without any further laser or surgical intervention. The cumulative success rate was 97.2% at 1 month, 93.3% at 3 months, 83.3% at 6 months, 78.7% at 12 months, and 71.5% at 24 months. Thus, the efficacy of cw Nd:YAG laser trabeculoplasty is comparable to that reported for trabeculoplasty performed using the argon laser (ALT), the Nd:YAG laser working in the free-running mode, and the diode laser. Biomicroscopy failed to reveal any serious inflammatory reactions persisting longer than 1 week. We conclude that cw Nd:YAG laser trabeculoplasty is a safe and effective alternative to ALT. PMID- 8515946 TI - Scleral flap sutures and the development of shallow or flat anterior chamber after trabeculectomy. AB - To determine whether closing the scleral flap with extra sutures can reduce the risk of overfiltration after trabeculectomy, we divided 339 trabeculectomies into three groups based on the number of scleral flap sutures used in the procedure, and studied the postoperative complications and results. The incidence of shallow or flat anterior chamber was significantly less in eyes that had received seven to nine sutures than in those that had received from two to six. Also, the incidence of cornea-lens touch was significantly less in the eyes with seven to nine sutures (P = .02, Fisher Exact Test). This study suggests that extra scleral flap sutures (in combination with laser suture lysis) is a safe and effective method of significantly reducing the risk of overfiltration after trabeculectomy. PMID- 8515947 TI - Posttrabeculectomy anterior subcapsular cataract formation induced by anterior chamber air. AB - We retrospectively examined the effect of air, as contrasted with balanced salt solution (BSS), sodium hyaluronate, or no substance at all, used to reform the anterior chamber at the end of trabeculectomy on subsequent cataract formation in 141 consecutive patients (173 phakic eyes). The minimum follow up was 120 days. The use of air increased the incidence of anterior subcapsular cataract formation significantly. Also, the eyes that had a large air bubble on postoperative day 1 had a higher incidence of anterior subcapsular cataract than the eyes with less air on that day. We suggest that the toxicity to the lens of the oxygen in the air increased the incidence of anterior subcapsular cataract in the eyes in which air was used. We recommend that BSS or sodium hyaluronate be used instead of air to reform the anterior chamber following trabeculectomy. PMID- 8515948 TI - Margins of safety in dacryocystorhinostomy. AB - We attempted to clarify the anatomic relationships of the lacrimal sac by performing standard orbital dissections to expose the lacrimal canaliculi, lacrimal sac, the ethmoid air cells, nasal septum, frontal sinuses, and the cribriform plate in five human cadaver heads; and then measuring the distance between the internal common punctum (ICP) and five key structures. The mean vector distance from the ICP to the anterior aspect of the cribriform plate was 25.1 +/- 2.95 mm. This measurement, along with the others, helps clarify osteotomy placement for dacryocystorhinostomy, so that, for example, cerebrospinal fluid leak can be prevented. Improved understanding of the anatomy of this region is also valuable in planning surgery for orbital and naso-orbital tumors, trauma, and congenital abnormalities. PMID- 8515949 TI - Temporary sutured tube-tarsorrhaphy: reversible eyelid closure technique. AB - Temporary closure of the eyelids is frequently recommended for ocular surface disorders in which reepithelialization of the cornea is problematic, as well as for acute Bell's palsy. We describe an easily performed technique of temporary tarsorrhaphy using plastic tubes sutured externally to the upper and lower eyelids, with eyelid closure accomplished by tightening a loop of suture passed through the two tubes. Corneal epithelial defects in 11 of 13 patients in whom we used this technique resolved satisfactorily without complications. In the remaining two, the polypropylene sutures eroded through the eyelids between 5 and 6 weeks after surgery. The sutured tubes loosened and the loosened sutures had to be replaced. In one patient, the overly long end of a suture rotated between the apposed eyelids, inducing a corneal abrasion, but no permanent damage to the eye. We conclude that the sutured tube-tarsorrhaphy provides excellent short-term closure of the eyelids, while allowing simple, painless opening for examining the globe. The risks of inflammation and infection associated with previously described techniques are minimized. PMID- 8515950 TI - Inadvertent cyclodialysis cleft. AB - We report four patients with functionally significant inadvertent cyclodialysis cleft. In three, the cleft followed uneventful extracapsular cataract extraction with posterior chamber intraocular lens implantation; in the fourth, blunt trauma with hyphema. Ocular hypotony resolved in three patients with medical therapy; the fourth required argon laser photocoagulation. Causes, clinical findings, and treatment of inadvertent cyclodialysis cleft are reviewed. PMID- 8515951 TI - Modified technique of blunt cannula retrobulbar anesthesia for vitreoretinal surgery. AB - We prospectively evaluated a modified version of a previously reported technique of retrobulbar anesthesia for vitreoretinal surgery involving the use of a blunt 19-gauge cannula to directly infuse anesthetic into the retrobulbar space. Using this method, 60 consecutive patients undergoing scleral buckling surgery had effective anesthesia and akinesia, with no complications. PMID- 8515952 TI - Using the oculocephalic reflex to assess effective retrobulbar anesthesia. AB - In order to confirm effective retrobulbar anesthesia, we attempted to stimulate the oculocephalic reflex (the doll's head phenomenon) in 40 consecutive patients undergoing elective cataract extraction with intravenous sedation. Thirty-nine of these 40 patients had a positive response, exhibiting the reflex in the nonanesthetized eye but not in the anesthetized eye. Using this test in sedated patients obviates interrupting surgery to administer additional block under less than optimal, uncontrolled conditions. PMID- 8515953 TI - Recurrent hyphema associated with IOL loop displacement treated with argon laser photocoagulation. AB - Recurrent late hyphema following cataract surgery and implantation of a posterior chamber intraocular lens (PC-IOL) is a rare complication, since there is usually no contact between the IOL and the anterior iris. If treatment with miotics or mydriatics fails, surgical removal of the IOL is often necessary. We report a patient with recurrent hyphema in his only myopic eye who had undergone two retinal detachment operations. A loop of the PC-IOL dislocated anteriorly through a peripheral iridectomy and caused localized pressure and recurrent bleeding. Conservative treatment with argon laser photocoagulation obviated more complex surgery in a high-risk patient. PMID- 8515954 TI - Pasteurella multocida keratitis and corneal laceration from a cat scratch. AB - A 24-year-old woman was evaluated 12 hours after she sustained a cat scratch to her left eye. Slit-lamp examination revealed a Seidel-positive corneal laceration with a surrounding dense full-thickness corneal ulcer and severe inflammatory reaction. Since the anterior chamber was well formed, it was decided not to repair the laceration on an emergency basis. She was initially treated with intensive topical fortified tobramycin and vancomycin, and intravenous gentamicin and clindamycin. Cultures of the corneal ulcer revealed Pasteurella multocida and the antibiotic regimen was adjusted appropriately. The laceration healed without surgery, and the infection resolved well, with excellent visual acuity. PMID- 8515955 TI - Repair of a disinserted scleral flap in trabeculectomy. AB - We report a surgical technique for repair of a disinserted scleral flap involving the use of two 10-0 nylon sutures, which are placed through the base of the scleral flap, and through and out of the peripheral cornea. These two sutures create a water-tight flap at the repaired hinged area. The procedure may thus continue as a trabeculectomy, permitting postoperative staged argon-laser suture lysis as well. PMID- 8515956 TI - Heterologous cartilage in sandwich lower lid reconstruction. AB - Postoperative healing in 15 patients in which Chondroplast, a heterologous irradiated bovine cartilage preparation, was used in conjunction with the "sandwich technique" to replace form-defining and supporting intrapalpebral lamella in connection with treatment of palpebral tumors, was uncomplicated, with no rejection to date. PMID- 8515957 TI - The McCoy Facial Trisquare: a useful instrument for measuring dystopia of the globe and canthi. PMID- 8515958 TI - Informed consent and making decisions for minors. PMID- 8515959 TI - Scholars and healers. PMID- 8515960 TI - Dyslexia and learning disabilities: an overview. AB - The concept and definition of dyslexia have been evolving for more than a century. Although it is certain that dyslexia is not a unitary syndrome, a comprehensive, testable definition has eluded us. Its characteristics have been differentially related to age; maturation of the brain and nervous system; auditory, visual, and intersensory processing; genetics; nutrition; and the environment. That we are dealing with an interdisciplinary disorder is beyond question. Optometrists do not treat dyslexia. They treat reading-disabled (RD) children who manifest some type of visual dysfunction that impairs their ability to respond to the specific instruction intended to remedy the disability. The papers in this Symposium are intended to provide a more precise understanding of the role of optometrists and other members of the interdisciplinary team in the management of dyslexic children. PMID- 8515961 TI - Dyslexic subtypes and severity levels: are there gender differences? AB - The prevalence of dyslexia among 100 children participating in a longitudinal study was examined. At age 10 years, The Dyslexia Screener (TDS) test, a direct assessment of coding skills used in reading and spelling, was administered. The incidence of suspected dyslexia of borderline or worse severity among boys and girls was not significantly different, nor did males and females differ significantly in terms of TDS-suspected dyslexic types of severity levels. Results challenge the widely held belief of an increased incidence of reading disability among males and, in conjunction with findings from other recent studies, underscore the need for establishing objective and reliable screening procedures in addition to teacher referral in identifying children in need of special services. Possible factors mediating previous estimates of incidence and the implications of these findings are discussed. PMID- 8515962 TI - The speech-language pathologist's role in an interdisciplinary approach to learning-disabled children. AB - Individual and environmental factors or characteristics influence disabled learners, particularly in reference to language disorders. An interaction of various fields is needed to minimize the impact of learning disabilities on a child's education and subsequent ability to communicate successfully. Various components of communication are affected by the inability to decode and encode language. Language areas most greatly influenced by learning disabilities are discussed. PMID- 8515963 TI - Diagnosis and management of reading dysfunction for the primary care optometrist. AB - A model for the identification/diagnosis and management of reading dysfunction for the primary care optometrist is presented. The model is based upon clinical experiences in both private and academic practice and an extensive review of the literature. The model, illustrated in a series of flow charts and a table, incorporates the major perceptual dysfunctions typically encountered by patients who present with reading problems. The first part of the model, labeled fundamental, demonstrates the minimum diagnostic and management techniques for those children who appear to have reading dysfunction. The second part of the model, labeled complex, provides a more extensive diagnostic and management approach. The validity of the approach is further illustrated in a series of 13 arbitrarily selected cases of reading dysfunction which are statistically analyzed. Robust correlations are found among different tests of visual-motor skills (Bender, Test of Visual Analysis Skills), a test of short-term memory (Getman-Henderson-Marcus Test of Visual Recall), and reading decoding. Modest correlation is also found between a test of auditory perception, The Test of Auditory Analysis Skills (TAAS) and reading decoding. Direct testing for dyslexia using the Dyslexia Determination Test illustrates that not all those with reading dysfunction are dyslexic. PMID- 8515964 TI - An analysis of the role of vision anomalies in reading interference. AB - Several reviews of the literature have shown a relation between vision anomalies and reading problems. The studies have been correlational - comparative in nature and thus have not established causal relations. This paper suggests that before experimental studies are conducted to establish causation, studies of the process by which vision anomalies produce reading interference need to be conducted. The paper discusses the factors to consider in studying vision and reading interference. The factors are: nature of the vision anomaly, type and severity of symptoms produced, type of reading interference (perceptual or functional deficiency), amount and type of near task demands, reading skill, and reading development stage. PMID- 8515965 TI - Dyslexia and visual perception: is there a relation? AB - Opinions differ concerning the relation between dyslexia and visual perception. In this pilot study we addressed this question by analyzing the results of visual perceptual testing on 19 elementary grade subjects diagnosed as having dyseidesia, one type of dyslexia that manifests as problems with sight-word recognition. The subjects, who have different degrees of severity of dyseidesia, were compared with 11 subjects tested as nondyslexic, but with reading problems. The Dyslexia Determination Test (DDT) and the Test of Visual Perceptual Skills (TVPS) were given to all subjects. Both multivariate analysis of variance (MANOVA) and univariate one-way analysis of variance (ANOVA) to test for differences in performance among four test groups (ranging from nondyslexic to increasing levels of severity of dyseidesia) showed no trends of either statistical or clinical importance. An individual with reading problems may be nondyslexic but have poor visual perceptual skills, or may be dyslexic with good visual perceptual skills. These results are consistent with the contention that reading problems caused by dyseidesia (as defined by the DDT) and those caused by visual perceptual deficiencies (as defined by the TVPS) are different. Although dyseidetic dyslexia results in characteristic coding patterns producing specific reading problems, it is probable that visual perceptual deficiencies contribute to learning problems that include general reading problems. Each condition would, therefore, require different forms of therapy. Limitations of this study and recommendations for future research are discussed. PMID- 8515966 TI - Correlation between cognitive processing and ocular motility. AB - The simultaneous and sequential cognitive processing model is useful in explaining the information processing strategies used by individuals for academic and other purposes. Simultaneous processing refers to handling of information in a holistic fashion with a strong visuospatial bias. Sequential or successive processing involves information handled in a linear, serial fashion with a strong temporal bias. There is no hierarchy of the cognitive processing systems. In this study it was found that sequential processing correlates with saccadic fixation and simultaneous processing correlates with self-generated ocular pursuits. PMID- 8515967 TI - Visual symptoms and reading performance. AB - Clinical observation indicates that visual asthenopic symptoms are frequently associated with reading for long periods of time. We investigated the relation between visual symptoms and standard measures of reading performance in 78 university students. The number of asthenopic complaints increased during the reading phase of the experiment and decreased during the relaxation phase. Overall, a weak but significant negative correlation was found between number of symptoms and reading rate on the Nelson-Denny reading test. The most symptomatic subjects scored lower on vocabulary and comprehension than the least asthenopic subjects. A limited retrospective analysis revealed no reading performance differences between subjects having normal binocular vision and those showing a minimum binocular dysfunction; however, the dysfunctional subjects reported more visual symptoms. This study suggests that visual symptoms are a factor in reducing reading performance, particularly in very symptomatic individuals. PMID- 8515968 TI - Dyslexia and learning disabilities: epilogue. PMID- 8515969 TI - Influence of soft contact lens design on clinical performance. AB - A double-masked, randomized study in four parts was conducted to evaluate the effect of varying certain soft contact lens design parameters on clinical performance. The effects of varying back optic zone radius (BOZR) (8.20 to 9.00 mm), back surface design (monocurve, bicurve, aspheric), edge thickness (0.12 to 0.24 mm), and back vertex power (+ 1.00 to -6.00 D) were investigated using test lenses manufactured in a high water content material. In each part of the study, between 20 and 35 volunteer subjects wore a range of lenses which were assessed after > 30 min settling periods. Postblink movement and lens "tightness" as assessed by the push-up test were unaffected by the variation in BOZR. Lenses of flatter BOZR centered lower and more temporally than steeper lenses. Lenses of similar back surface sagittal depth, but differing in terms of back surface design, did not center the same; the monocurve lenses decentered more than bicurve or aspheric lenses. Edge thickness had no significant effect on comfort or lens fit. Plus power lenses resulted in more postblink movement than minus lenses of similar power. The results are discussed in relation to the design and fitting of soft contact lenses. PMID- 8515970 TI - Optics of phakic, pseudophakic, and aphakic eyes: effects on the Stiles-Crawford (SCE I) function. AB - In many experimental situations one has to work with suitable optical corrections for ocular elements which have been eliminated (lens in aphakia, for example). Analysis of the optics of the total system (eye plus correction and other optical elements) shows substantial changes in the positions of the cardinal points. These changes are meaningful and must be taken into account in subsequent analysis. We discuss the pertinent optical considerations and show as an example the results of measurements of the Stiles-Crawford effect of the first kind in an aphakic subject with spectacle and contact lens correction. PMID- 8515971 TI - Recommended coordinate systems for thin spherocylindrical lenses. AB - Because the set of thin spherocylindrical lenses forms a vector space, any such lens can be expressed in terms of its cartesian coordinates with respect to whatever set of basis lenses we may choose. Two types of cartesian coordinate systems have become prominent, those having coordinates associated with the lens power matrix and those having coordinates associated with the Humphrey Vision Analyzer. This paper emphasizes the value of a particular cartesian coordinate system of the latter type, and the cylindrical coordinate system related to it, by showing how it can simplify the trigonometry of adding lenses and how it preserves symmetry in depicting the sets of all spherical lenses, all Jackson crossed-cylinders, and all cylindrical lenses. It also discusses appropriate coordinates for keeping statistics on lenses and shows that an easy extension of the lens vector space to include general optical systems is not possible. PMID- 8515972 TI - Comparison of fixation disparity measurements obtained with the Wesson Fixation Disparity Card and the Sheedy Disparometer. AB - We compared the fixation disparity measurements obtained with the Disparometer to those of the Wesson Card. Previous studies suggest that the measurements obtained by these two instruments gave different results. The results of previous studies were based on the analysis of pooled data, which may have led to spurious results. Analysis of our data done in this manner (pooled data) revealed the same findings. However, after analysis of the data based on the separation of subjects according to phoria (exophoria/esophoria), no statistically significant difference was found between the measurements obtained with the Wesson Card and those with the Disparometer. PMID- 8515973 TI - Measurement of Friedmann Visual Field Analyzer tests in primary open-angle glaucoma. AB - A method is described to allow an IBM PC/AT compatible microcomputer program to compute a score from the visual field data collected from a standard Friedmann Visual Field Analyzer (FVFA) Mk II testing procedure. The method could, in principle, be applied to any visual field data which provide quantitative information on the sensitivity of different retinal locations. The score takes into account the depth of any defects, their position in the visual field, and the clustering of defects into scotomata. Visual fields in 119 normal eyes, 82 ocular hypertensive (OH) eyes, and 75 glaucomatous eyes were assessed to provide the data necessary to implement this method. Analyzing the frequency of missed points against point luminance demonstrates that the most effective cut-off from which to regard points as defective is a miss at 0.8 log units or more above the working threshold. A statistical method of analyzing the distribution of defects following Bayesian principles is described and shows that points in the superior nasal, superior arcuate, and inferior arcuate areas provide the most information for detecting glaucoma. The program, written in Turbo Pascal v5.5, incorporates these findings in producing the score. PMID- 8515974 TI - Prevalence of disabled stereopsis. PMID- 8515975 TI - A research agenda to address challenges facing oral and maxillofacial radiology. PMID- 8515976 TI - Effect of screw number on reconstruction plating. AB - Recently sacrificed bovine ribs and a hydraulic press were used to evaluate the effect that the number of screws has upon reconstruction plating. Reconstructed segments were subjected to five trials each for one, two, three, four, five, six, seven, and eight screws with increasing weights until failure. Increasing the number of screws increased the amount of weight resisted up to four screws per segment after which no additional benefits were realized (P < .001). PMID- 8515977 TI - Placement of an endosseous implant in a growing child with ectodermal dysplasia. AB - This article reports placement of a single mandibular endosseous implant in a 5 year-old patient with hypohidrotic ectodermal dysplasia and oligodontia. This congenital anomaly does not appear to retard healing and the osseointegration remains after 5 1/2 years of loading. Surgical, prosthodontic, and growth and development considerations are presented. PMID- 8515978 TI - Self-stabilizing approach to surgical uprighting of the mandibular second molar. AB - A technique for surgical uprighting of malposed mandibular second molars is described. The principal advantage of this technique is that the tooth is stabilized by bone on the distal aspect of the uprighted tooth. Long-term clinical and radiographic follow-up reveals positional stability and no adverse pulpal or periodontal sequellae. PMID- 8515979 TI - Ibuprofen controlled-release formulation. A clinical trial in dental impaction pain. AB - This double-blind study compared a controlled-release formulation of ibuprofen 600 mg with three doses of regular ibuprofen 200 mg and three doses of codeine 30 mg. Patients who had dental impaction surgery received the controlled-release ibuprofen, codeine, or regular ibuprofen when postoperative pain reached moderate to severe intensity. At 4 and 8 hours after dose 1, patients who had initially received the controlled-release ibuprofen received a placebo, and those taking ibuprofen and codeine received their second and third doses of those drugs. All doses of study medication or placebo appeared identical for each treatment. Subjects made evaluations hourly for 12 hours in a diary. The controlled-release ibuprofen had a comparable onset to ibuprofen, a higher peak effect, and was significantly more effective than ibuprofen at hour 4; the controlled-release ibuprofen was significantly more effective than codeine for all hourly observations through hour 9. Ibuprofen was significantly better than codeine only through hour 3. The controlled-release ibuprofen had the lowest incidence of side effects and codeine the highest. The single dose of the controlled-release ibuprofen formulation appeared as efficacious as three regular doses of ibuprofen 200 mg over a 12-hour period. PMID- 8515980 TI - Surgical correction of an equine deviated anterior maxilla. AB - The surgical correction of midfacial deformities of the horse have rarely been undertaken. This article describes the successful management of a submucous cleft of the maxilla in a young colt. Details of the operative and perioperative medical and surgical management are described. The horse, now 5 years of age, has sired eight normal progeny. PMID- 8515981 TI - Pedunculated cavernous hemangioma. A case report. AB - A rare case of pedunculated hemangioma of the oral mucosa has been reported. Clinically, it was diagnosed as a fibroma induced by irritation, but histologic examination followed to excisional biopsy demonstrated that it was a cavernous hemangioma. PMID- 8515982 TI - Oral manifestations of cutaneous T-cell lymphoma. A report of eight cases. AB - Cutaneous T-cell lymphoma rarely involves the oral cavity. Only 14 detailed cases of oral cutaneous T-cell lymphoma have been described in the English-language literature; this report describes eight additional cases observed among 824 patients evaluated at our cutaneous T-cell lymphoma center since 1968. Oral involvement occurs late in the course of cutaneous T-cell lymphoma and usually is associated with poor prognosis; most patients die of disease complications within 3 years of the diagnosis of oral involvement. PMID- 8515983 TI - Skin testing after anaphylactoid reactions to dental local anesthetics. A comparison with controls. AB - Reactions to scratch and intradermal challenge with a variety of local anesthetics were examined in 90 patients and compared with 45 controls. The frequency of a positive scratch test was 13 of 90 in the patient group and 12 of 45 in the control group. Thus scratch testing did not appear to discriminate between test and control groups. Significantly greater numbers of patients (22 of 90) gave a positive intradermal response than controls (4 of 45) (chi-squared test p < 0.05). Nine patients showed reactions to more than one agent. The majority of reactions in both patients and controls were in atopic subjects (chi squared test p < 0.05). In 87 of the 90 patients with suspected anaphylactoid reactions to local anesthetic agents, negative skin reactions to at least one of the agents allowed intrabuccal challenge and subsequent recommendation of an agent for future use. Skin testing, though not providing formal proof of allergy, provides a useful test to indicate local anesthetics that may be used for future procedures. PMID- 8515984 TI - Recurrent idiopathic trigeminal sensory neuropathy. AB - Idiopathic trigeminal neuropathy is a rare disorder characterized by transient sensory disturbances in the territory of one or more branches of the trigeminal nerve. Acute and chronic forms of the disease have been recognized, but to our knowledge no recurrent cases have been reported. Two cases of recurrent idiopathic trigeminal sensory neuropathy are reported. The patients presented sensory alterations limited to the territory of the trigeminal nerve in the absence of other clinical features. In both cases sensory disturbances began in the tongue and lips and later spread throughout the face. The whole trigeminal nerve territory was involved in the first patient, but in the second patient only the second and third trigeminal branches were affected. There was no muscle weakness or pain, and the corneal reflex was present in both patients. The first patient recovered completely after 3 months, but the symptoms recurred in a similar fashion 3 years later. In the second patient the symptoms occurred each winter for more than 10 years. The conditions in these two patients could be considered as recurrent idiopathic forms of trigeminal sensory neuropathy. PMID- 8515985 TI - Eosinophilic ulcer of the oral mucosa. Report of 38 new cases with immunohistochemical observations. AB - Eosinophilic ulcer of the oral mucosa (traumatic eosinophilic granuloma) mimics oral cancer clinically and is occasionally misdiagnosed as lymphoma on microscopic examination. Trauma is believed to play a role in its development, but its exact pathogenesis is not known. The demographic, clinical, and histologic features of 38 previously unreported cases of eosinophilic ulcer of the oral mucosa are reviewed. Nine representative cases were studied immunohistochemically. Microscopically, the lesions contained a polymorphic inflammatory infiltrate extending deep into the submucosa, underlying muscle, and salivary glands. Numerous eosinophils and large mononuclear cells with pale nuclei and frequent mitoses were seen in all lesions. Lymphocytes, histiocytes, plasma cells, granulocytes, and mast cells were also present. Immunohistochemical stains showed that the lymphocytic infiltrate was composed predominantly of T cells. T-cell-specific antigen-presenting cells were more numerous than the non antigen-presenting cell type. The large cells with pale nuclei stained positively only for vimentin; the possible myofibroblastic nature of these cells is discussed. Although trauma might have an etiologic role, the pathogenesis of eosinophilic ulcer of the oral mucosa is probably T cell mediated. PMID- 8515986 TI - Early oral presentation of lues maligna in a patient with HIV infection. A case report. AB - We present a case of a patient infected with the human immunodeficiency virus who developed syphilis manifested by atypical early oral and skin ulcerations. The profound immune defects associated with human immunodeficiency virus may lead to an altered clinical presentation and a more aggressive course in patients infected with Treponema pallidum. The unusual clinical manifestations observed in this case emphasize the importance of considering secondary syphilis in the differential diagnosis of any inflammatory mucosal and skin disorder in patients with the human immunodeficiency virus. PMID- 8515987 TI - Squamous odontogenic tumor. Report of three cases including the first extraosseous case. AB - Squamous odontogenic tumor is a distinct entity-separate from the more aggressive ameloblastoma. Only 33 squamous odontogenic tumors have been reported since the first description in 1975. We report three additional cases including the first completely extraosseous case. PMID- 8515988 TI - Lingual mandibular sequestration and ulceration. AB - This study analyzed 11 patients who had small sequestra associated with ulceration of the lingual mucosa in the posterior mandibular molar area at the level of the mylohyoid ridge. The patients were adults (mean age, 45.3 years) with complaints of sensitive, occasionally painful lesions that appeared for periods that ranged from 1 week to several months. No abnormalities were evident on periapical radiographs; however, in three cases in which occlusal radiographs were available, small irregular radiopacities contiguous with the cortex were noted. Spontaneous exfoliation or surgical removal of the sequestrum resulted in resolution of the lesion. The possible etiologic factors associated with this apparent clinical-pathologic entity are discussed. PMID- 8515989 TI - Catalase protection against hydrogen peroxide-induced injury in rat oral mucosa. AB - Hydrogen peroxide in contact with the oral mucosa induces vesicle formation and ulceration. This study assesses the protective effect of catalase against the hydrogen peroxide insult in the rat tongue mucosa. In addition, we report a detailed histologic characterization of the mucosal injury. Four repetitive applications of 30% hydrogen peroxide at 15 minute intervals produced a vast edema of the submucosal tissue including the tongue muscles that was seen immediately after the last application. Histomorphometric measurements indicated a substantial regression of the edema 1 day later with the appearance of a very large ulceration lined by a pyogenic membrane. Animals examined 7 days after the hydrogen peroxide administration revealed almost complete healing in terms of absence of edema and renewal of intact epithelial lining. Catalase applied to the tongue before the hydrogen peroxide fully prevented the pathologic tissue reaction. Thus testing of the clinical feasibility of catalase in protecting the oral mucosa against hydrogen peroxide-induced injury is strongly indicated. PMID- 8515990 TI - Use of dental operating microscope in endodontic surgery. AB - Endodontic surgery is an alternative therapeutic approach to endodontic treatment. The outcome of the technique is affected by several factors, some of which can be eliminated by the use of a dental operating microscope. The microscope was used during the performance of 50 apicoectomies, with or without retrograde fillings. For clinical evaluation cases treated with the dental operating microscope were compared to cases treated without it. The postoperative evaluation showed a reduced incidence of symptoms in the cases treated with the dental operating microscope. More important, the dental operating microscope enhanced and facilitated each phase of endodontic surgery. Its use is highly recommended. PMID- 8515991 TI - Nasopharyngeal carcinoma. Computed tomographic imaging of four cases. AB - Nasopharyngeal carcinoma occurs with great frequency in Asia. It is an infiltrative tumor that often produces no symptoms early in its course. However, the proximity of the nasopharynx to the nasal cavity, eustachian tubes, masticatory muscles, and cranial nerves can allow extension of the lesion into these structures, resulting in numerous maxillofacial abnormalities. Computed tomography is effective in imaging the development of nasopharyngeal carcinoma in the nasopharynx as well as the subsequent spread of the neoplasm to adjacent areas. Four cases of nasopharyngeal carcinoma are presented in which computed tomography provides an accurate assessment of the extent of the tumor and allows correlation with clinical manifestations. PMID- 8515992 TI - Noise in D- and E-speed radiographic film. AB - The purpose of this investigation was to compare image noise in D- and E-speed radiographic film and to establish a basis for choosing a particular speed of film for study of trabecular changes in alveolar bone. Eleven D-speed and 11 E speed radiographs were made at varying exposures and developed along with unexposed film of each type to produce uniform optical densities that range from approximately 0.05 to 2.5. Profiles (scan lines) were made of each film at a spatial resolution of 0.02 mm. Noise was quantified for each profile using three measures: the standard deviation of the profile pixel intensity, I(x), about the mean, I(x); the coefficient of variation of I(x) about I(x); and Wiener spectral analysis. Results indicate that the average magnitude of noise for D- and E-speed film over this range of optical densities exceeds 4% and 6%, respectively; the average noise content of E-speed film was 25% to 35% greater than D-speed; and noise energy of both films is concentrated at low spatial frequencies and low optical densities. PMID- 8515993 TI - Panoramic mandibular index and bone mineral densities in postmenopausal women. AB - The panoramic mandibular index was used in a group of postmenopausal women to determine whether it correlates with bone mineral densities of the femoral neck, lumbar area, and the trabecular and cortical parts of the mandible. The bone mineral density values were measured by dual-energy x-ray absorptiometry of the femoral neck and lumbar area and by quantitative computed tomography of the mandible. Linear correlation of the panoramic mandibular index with all bone mineral density values was weak. However, the low and high index subgroup means were clearly dependent on the bone mineral density variables. PMID- 8515994 TI - Radiation exposures around a panoramic dental x-ray unit. AB - To evaluate the radiation hazard in the vicinity of a panoramic x-ray unit, Ektaspeed periapical films were placed in an array behind and to the side of the unit. They were left in place for 7 months, during which 1414 examinations were carried out. The maximum exposure at 80 cm from the patient was determined to be about 1 mGy in 7 months with a heavy workload. This shows clearly that no special environmental shielding barriers are necessary around this unit. PMID- 8515995 TI - Bony exostosis of the mandibular condyle. PMID- 8515996 TI - Medical/dental management of a chronic hepatitis C patient. A case report. AB - Hepatitis C accounts for 20% to 40% of all acute viral hepatitis, with between 150,000 and 170,000 new cases reported in the United States each year. Approximately 50% of these patients will progress to chronicity with potential hepatic disorders. In an average dental practice that treats 20 patients each day, it is estimated that one hepatitis C patient will be encountered every 2 weeks. Because numerous dental procedures stress the immune, coagulation, and metabolic systems, a thorough understanding of the potential complications imposed by hepatitis C to these systems is essential. This case study encompasses comprehensive medical and dental management of the chronic hepatitis C patient. It includes assessment, intervention, and evaluation, as well as projected planning for future treatment. PMID- 8515997 TI - Ataxia-telangiectasia. Review of the literature and a case report. AB - Cutaneous vascular abnormalities are frequently detected on initial examination of newborns. Many of these lesions are common variations of normal lesions such as nevus simplex and strawberry hemangiomas. Some of the vascular abnormalities, however, are a feature of a number of syndromes with multisystemic involvement. These syndromes have been described under the heading of neurocutaneous diseases. Ataxia-telangiectasia is a neurocutaneous syndrome that appears with progressive cerebellar ataxia, oculocutaneous telangiectasias, and abnormalities of many other organs. Oral mucosa is also affected. Current concepts on the pathogenesis of ataxia-telangiectasia and one case of the disease are presented in this article. PMID- 8515998 TI - Interview with Aram Glorig, MD. Interview by Howard P. House, MD. PMID- 8515999 TI - Auditory brainstem implant: I. Issues in surgical implantation. AB - Most patients with neurofibromatosis type 2 (NF2) are totally deaf after removal of their bilateral acoustic neuromas. Twenty-five patients with neurofibromatosis type 2 have been implanted with a brainstem electrode during surgery to remove an acoustic neuroma. The electrode is positioned in the lateral recess of the fourth ventricle, adjacent to the cochlear nuclei. The present electrode consists of three platinum plates mounted on a Dacron mesh backing, a design that has been demonstrated to be biocompatible and positionally stable in an animal model. Correct electrode placement depends on accurate identification of anatomic landmarks from the translabyrinthine surgical approach and also on intrasurgical electrophysiologic monitoring. Some tumors and their removal can result in significant distortion of the brainstem and surrounding structures. Even in the absence of identifiable anatomic landmarks, electrode location can be adjusted during surgical placement to find the location that maximizes the auditory evoked response and minimizes activation of other monitored cranial nerves. Stimulation of the electrodes produces auditory sensations in most patients, with results similar to those of single-channel cochlear implants. A coordinated multidisciplinary team is essential for successful application of an auditory brainstem implant. PMID- 8516000 TI - Auditory brainstem implant: II. Postsurgical issues and performance. AB - The auditory brainstem implant (ABI) restores some hearing sensations to patients deafened by bilateral acoustic tumors. Electrodes are stable for more than 10 years. In most cases nonauditory side effects can be avoided by judicious selection of the stimulating waveform and electrode configuration. Most perceptual measurements demonstrate that the ABI produces psychophysical and speech performance similar to that of single-channel cochlear implants. ABI patients receive suprasegmental information in speech and significant enhancement of speech understanding when the sound from the ABI is combined with lipreading. PMID- 8516001 TI - Interdisciplinary approach to functional voice disorders: the psychiatrist's role. AB - A review is given of the experience obtained over 6 years of having a psychiatric consultant available as part of the staff of the Voice Clinic, to which more than a thousand patients have been referred. The presenting features in a case that should alert the otolaryngologist to the need for psychiatric consultation and possible treatment are noted. Suggestions are made as to how to prepare the patient for the referral to a psychiatrist with the appropriate interests and willingness to collaborate closely with the otolaryngologist and the speech pathologist. PMID- 8516002 TI - Laser cordectomy or radiotherapy: cure rates, communication, and cost. AB - Health care costs have risen dramatically in recent years. Cost-containment strategies have become necessary to ensure that adequate medical care is accessible to all who need it. These strategies include choosing the least costly of several treatment modalities with equal efficacy. Radiotherapy has been considered by some as the treatment of choice for early glottic tumors. Rationale for this is based on two major assumptions: that cure rates are equal for radiotherapy and surgery, and that voice preservation and quality is superior with radiotherapy. Implicit in these assumptions is the idea that cost of therapy should not be a factor in selecting an alternative. This study presents a literature review of cure rates for laser cordectomy and radiotherapy for T1 glottic cancers. An objective voice analysis was performed on 14 patients with T1 glottic cancers treated with laser cordectomy and the results were compared to a group of 20 patients treated with radiotherapy for similar early tumors. Finally, the average total cost of each modality was calculated and compared. Our findings indicate that: (1) cure rates are equivalent; (2) voice quality after laser cordectomy is as good as that noted after radiotherapy; and (3) total cost of therapy is much less for laser cordectomy than for radiotherapy. We advocate laser cordectomy rather than radiotherapy for most early glottic tumors. PMID- 8516003 TI - Dental status and oral hygiene in patients with head and neck cancer. AB - Poor oral hygiene is believed to play a role as a risk factor for head and neck cancer, especially for oral cancer. Only few epidemiologic data exist about dental status and oral hygiene in these patients. We performed a case-control study involving 100 patients with squamous cell carcinoma of the upper aerodigestive tract and 214 age- and sex-matched control subjects with no known tumorous disease. In the tumor patients, oral hygiene and dental status proved to be significantly worse: the majority of the tumor patients seldom or never brushed their teeth and the frequency of dental visits was significantly lower. Tartar of 3 mm or more was found in 40.9% of the tumor patients and in 22% of the control subjects. In the tumor group, the incidence of decayed teeth was significantly higher compared with the control subjects. Chronic inflammation of the gingiva was observed in 28% of the tumor patients vs. 13.5% in the control group. Oral hygiene was negatively correlated with alcohol as well as with tobacco consumption. The social status of subjects also correlated with oral hygiene, which was found to be worst in subjects from the lower social strata. The present study revealed a poor dental status and oral hygiene in patients with head and neck cancer. The pathogenetic mechanism being associated with this suspected risk factor remains to be investigated. PMID- 8516004 TI - Hearing preservation using the modified translabyrinthine approach. AB - Removal of an acoustic neuroma using the translabyrinthine approach has previously been considered "incompatible" with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed two intracanalicular acoustic neuromas that originated from the inferior vestibular nerves, and preserved serviceable hearing in the ears operated on. This report represents the preliminary findings using this particular technique in the management of intracanalicular acoustic neuromas. PMID- 8516005 TI - Otologic neurotologic manifestations of HIV-related disease. AB - Human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), has reached worldwide epidemic proportions and is increasing. Otologists, neurotologists, and audiologists practicing in metropolitan centers in North America can expect to encounter patients with HIV related illnesses, including patients with AIDS-related complex (ARC) and AIDS. Five representative cases are presented: chronic otitis media, facial palsy, Gradenigo's syndrome with facial paralysis, otosyphilis, and Kaposi sarcoma of the mastoid. The common link in all cases was HIV infection. This presentation discusses the management of several HIV-infected patients with otologic and neurotologic findings. HIV infection has extended to all parts of North America. The worldwide incidence is increasing. As the epidemic continues to unfold, new challenges to both the diagnosis and treatment of otologic and neurotologic disease in HIV-positive patients will confront the audiologist and otolaryngologist. Recommendations for the safety of the examining audiologist and treating physician are given. PMID- 8516006 TI - Indications, evaluation, complications, and results of functional endoscopic sinus surgery in 200 patients. AB - Functional endoscopic sinus surgery (FESS) is a new and exciting treatment for chronic sinus disease. Our knowledge of the surgery continues to expand. A retrospective and prospective review of 200 patients undergoing FESS was undertaken at the Houston Ear, Nose, and Throat Clinic. Parameters studied included patient symptoms, medical history, medical therapy, and radiologic findings. Also reviewed were length of hospitalization, complications, and postoperative symptoms. Nasal obstruction was the most common preoperative symptom. Anterior ethmoid and ostiomeatal complex disease were the most common preoperative CT scan findings. More than 84% of the surgeries were performed on an outpatient basis. Minor complications developed in 8% of the patients, and only one major complication occurred (0.05%). With a mean followup of 17 months, 88% of the patients were symptom-free or improved; however, 41.5% still required some medical therapy. FESS can safely be performed while the patient is under general anesthesia. Partial middle turbinectomy is a safe and recommended procedure; no cases of atrophic rhinitis occurred. We conclude that FESS is a highly successful treatment for chronic sinus disease (p < 0.01) and that a strong patient history for sinus symptoms is the most important indication for FESS. PMID- 8516007 TI - Sinonasal undifferentiated carcinoma: a ray of hope. AB - In 1987, we published a case series of a newly-described, highly malignant neoplasm, termed sinonasal undifferentiated carcinoma, in which treatment results were poor. In this updated study, we report the followup for the original three surviving patients and for six additional cases whose tumors were diagnosed between January 1987 and October 1991. These data suggest that the prognosis for patients with localized disease may be better than originally described. PMID- 8516008 TI - Middle ear ventilation with HydroxylVent tube: review of the initial series. AB - Thirty HydroxylVent tubes were implanted in twenty-seven patients. The chief indications were unresolving eustachian tube dysfunction, with either collapse or perforation of the tympanic membrane. Every patient had undergone a lengthy course of treatment with conventional ventilation tubes. Twenty ears (66%) showed good results, with prolonged ventilation and restoration of middle ear function. Two tubes appeared to be open, with the development of a pinpoint perforation of the drum. Eight tubes occluded as a result of displacement of the tube, middle ear pathology, or debris. Indications and techniques of management are discussed, along with an analysis of complications. PMID- 8516009 TI - Analysis of DNA content in supraglottic epidermoid carcinoma. AB - DNA analysis by flow cytometry is considered to be of prognostic value in epidermoid carcinoma of the head and neck. However, few and contradictory studies have been made on laryngeal carcinomas. We studied 48 epidermoid carcinomas in patients subjected to horizontal supraglottic laryngectomy with a 5-year- followup. The technique described by Hedley for fixated and paraffin-embedded tumors was used. Thirteen tumors were excluded on the grounds of presenting variation coefficients in excess of 10. Of the 35 cases analyzed, 28 (80%) were diploid and seven (20%) aneuploid. No correlation was observed between tumor ploidy and patient survival, recurrence, or any of the histopathological variables studied. PMID- 8516010 TI - The presence of eosinophil cationic protein in middle ear effusion. AB - Eosinophil cationic protein (ECP) is probably responsible for the underlying inflammatory mechanisms seen in asthma. It can be modulated in vivo by immunotherapy or steroids, with an appropriate reduction in symptoms of respiratory tract diseases. ECP is an identifiable mediator in additional target organs involved in allergic reactions, making it of potential interest in the study of otitis media with effusion. A qualitative prospective study was designed to discover the relationship of ECP and serum IgE in patients with middle ear effusion and allergy, as demonstrated by RAST and skin testing. The concentrations of ECP in the middle ear fluid from 23 consecutive patients with otitis media with effusion undergoing the placement of tympanostomy tubes ranged from 2 to 1248 micrograms (normal serum ECP, 5 to 15 micrograms), with 87% being abnormally elevated. There was no correlation between an individual's ear and serum levels of ECP (r = 0.1672; p = 0.6232), suggesting a more localized process. There was no relation between effusion ECP and serum IgE (p = 0.0040). ECP from middle ear effusion did correlate with a patient's having allergy, as confirmed by RAST and skin testing (p = 0.0095). Mechanisms involving immune mediated disease in the middle ear, of which the eosinophil may be one participant, are presented. PMID- 8516011 TI - DNA content and tumor response to induction chemotherapy in patients with advanced laryngeal squamous cell carcinoma. AB - Recent results indicate that the adjusted DNA Index (aDI), a measure of nuclear DNA content, is a significant prognostic factor for patients with advanced laryngeal cancer treated with surgery and radiation therapy. Because DNA aneuploidy is an indirect measure of the proliferative activity of a cell population, a study was conducted to examine differences in tumor response to induction chemotherapy based on aDI values. Pretreatment tumor specimens were obtained from 50 patients with stage III and IV laryngeal squamous cell carcinoma who underwent induction chemotherapy (cisplatin/5-FU). With the use of computerized cytomorphometry, DNA content and nuclear area were measured and associations with tumor site, stage, chemotherapy response, tumor recurrence, and survival were examined. An elevated aDI was more frequent in patients with a chemotherapeutic response (p = 0.08), and mean aDI was higher among the complete responders. There were no complete responders among patients with a low aDI value (< 0.024). Neither aDI nor nuclear area correlated significantly with organ preservation or patient survival. Our results indicate that a complete response is more likely for patients with tumors with an elevated aDI and that pretreatment aDI may be useful in selecting high-risk patients who might benefit from chemotherapy. PMID- 8516012 TI - An animal model for pharyngocutaneous fistulas. AB - Postoperative pharyngocutaneous fistula is not an uncommon complication. Although the frequency of postoperative fistulae has decreased with the use of perioperative broad-spectrum antibiotics, it remains a complication with significant morbidity and expense. We present an animal model for postoperative pharyngocutaneous fistulae based on increasing wound tension. The New Zealand white rabbit was used to assess the rate of wound breakdown in the thyrohyoid membrane. The animals were assigned to one of seven groups according to the width of tissue resected. After tissue resection, the pharyngeal wounds were repaired, as were the overlying skin wounds. Animals were monitored postoperatively up to 14 days, at which time they were killed and underwent autopsy. Statistically significant results were achieved that demonstrate an increasing incidence of pharyngeal wound breakdown associated with increasing width of tissue resected and, therefore, closure tension. The procedure and results will be presented in detail. We propose that this model may be used to assess postoperative wounds as well as substances or methods touted as promoters of wound healing. PMID- 8516013 TI - Literature review articles as a research form. AB - The purpose of this article has been to outline the JOURNAL format, to present some methodologic suggestions for this new section, and, hopefully, to excite and challenge authors to this form of research. Fundamental to a quality overview are A PRIORI EXPLICIT CRITERIA for each component of the review process. Details of what this means have been presented. The length of the review will depend on the objectives; however, approximately 20 double-spaced manuscript pages (about eight published pages) should be considered close to maximal for a readable review. References may be too extensive for full publication; one way to manage this is to choose about 50 or less key references for publication and suggest to the readers that a full bibliography is available, upon request, from the corresponding author. We hope this new section will be exciting and will be of benefit. PMID- 8516014 TI - Clinical tutorials: rationale and technique. PMID- 8516015 TI - Frey's syndrome secondary to a subcondylar fracture. PMID- 8516016 TI - Middle ear adenoma: report of two cases. PMID- 8516017 TI - Laryngocele: a cause of stridor and airway obstruction. PMID- 8516018 TI - Topical anesthetic-induced methemoglobinemia: a case report and review of the literature. PMID- 8516019 TI - Corticosteroids in rhinology. PMID- 8516020 TI - Speaking tubes for office use. PMID- 8516021 TI - Carcinoma of the upper gum. PMID- 8516022 TI - Collagenous spherulosis of the breast with atypical epithelial hyperplasia. AB - Collagenous spherulosis of the breast is a recently described lesion that was previously been seen only in a setting of benign, typical epitheliosis. We report that unusual case of a collagenous spherulosis of the breast in association with severely atypical epithelial hyperplasia in a 45-year-old woman. The patient presented an asymptomatic right lump and underwent a wide breast tissue resection. After a postoperative follow-up of twelve months, the patient remained well with no breast symptoms. Since atypical hyperplasia in the breast is considered predictive of relatively high risk of later carcinoma development, the finding of collagenous spherulosis with atypical hyperplasia should suggest a long-term follow-up. although at present the biological and prognostic significance of this association is unknown. PMID- 8516023 TI - Bilateral leiomyoma of the epididymis. AB - The rare event of a bilateral leiomyoma of the epididymis is illustrated. The tumors were located near the tail of the epididymis in a man aged 58, which furthermore presented hydrocele and had been previously operated because of bilateral inguinal hernia. The differentiation with inflammatory pseudotumor, leiomyosarcoma and adenomatoid leiomyoma is discussed. PMID- 8516025 TI - [Juvenile xanthogranuloma. Description of a case with liver involvement]. AB - Juvenile Xanthogranuloma. Report of a case with hepatic involvement. The Authors present a case of Juvenile Xanthogranuloma (JX) in a 3 months female child with cutaneous and hepatic nodules associated to dyspnea attributable to obstructive bronchopneumopathy. Histologically the lesions are xanthomatous with proliferation of fat-laden histiocytes. The hepatic involvement is characterized by hepatomegaly and yellow nodules on liver surface as seen at laparoscopy. On liver biopsy there is remarkable expansion of portal triad caused by aggregates of large foamy mono-polynuclear histiocytes with Touton giant cells. The cutaneous nodule biopsy shows histiocytic infiltrate in inter-adnexal dermal space with many giant cells holding great lipidic vacuoles. The patient's follow up is characterized by slow and progressive clinical improvement with resolution of cutaneous, hepatic and pulmonary pathology. The Authors emphasize the differential diagnosis between this systemic form of JX and Langerhans cell Histiocytosis (Histiocytosis X) with multiorgan involvement. This diagnosis is necessary in order to establish therapy and prognosis. PMID- 8516024 TI - Morphometric assessment of nucleolar activity in liver cells during the evolutive pathway of chronic hepatitis C to cirrhosis. AB - Using a computer-assisted image analysis system, we performed a morphometric study of silver-stained nucleoli of hepatocytes in liver biopsy specimens from hepatitis C virus-positive patients with chronic persistent hepatitis (3 cases), chronic active hepatitis (4 cases), and cirrhosis (4 cases). The number and the total area of nucleoli, the average area of each nucleolus and the nuclear area were determined for each of 100 hepatocytes per case. A continuing increase in the area of both nucleoli and nuclei paralleled a progressive decrease in the number of nucleoli during the evolution of chronic hepatitis C to liver cirrhosis. These findings would indicate that the hepatitis C virus-induced liver damage causes reactive changes in surviving hepatocytes resulting in an increased nucleolar biosynthetic activity rather than in an increment of cell proliferation rate. Therefore, the liver response to hepatitis C virus injury seems to be mainly based on a condition of cell "hypertrophy", whereas we previously showed that a process also of compensatory hyperplasia occurs in chronic hepatitis B, possibly resulting from a different pathogenesis of the viral damage. PMID- 8516026 TI - [Cardiac metastasis of malignant melanoma]. AB - Cardiac metastatic malignant melanoma. Secondary tumors frequently involve the heart, but the main data about incidence, rate and localization into the specialized myocardium are poor and fragmentary. Post-mortem examination of the conduction system of arrhythmic hearts was studied in two cases of malignant melanoma. In the first case signed by AV block and fibrillation, metastases involved the myocardium over atrioventricular (AV) node and the left and right bundle branch (L and RBB). The second case had not arrhythmias in the clinical picture, but a large metastatic mass involved the junctions between sinoatrial (SA) node and myocardium of the crista terminalis, the junctions between atrium and AV node and the left branch. PMID- 8516027 TI - Thoracic aortic calcification in 3 children with candidiasis-endocrinopathy syndrome. AB - Three cases are reported of the association of childhood onset of thoracic aortic calcification with mucocutaneous candidiasis, endocrine dysfunction and recurrent non-fungal pulmonary disease. The aortic calcification affects the thoracic aorta and the low lumbar aorta and common iliac arteries, sparing the mid-lumbar aorta and its major branches. Ischemic signs and symptoms of the head and neck and lower limbs are absent. This peculiar, slowly progressive vascular calcification, although unexplained to date, appears to be a non-random part of the more common candidiasis-endocrinopathy syndrome. PMID- 8516028 TI - Disseminated histoplasmosis in chronic mucocutaneous candidiasis. AB - Chronic mucocutaneous candidiasis (CMC) is rarely associated with disseminated Candida, but is often associated with systemic infection secondary to other organisms [1]. A 6-year-old with CMC and disseminated histoplasmosis is presented here. PMID- 8516030 TI - Mesomelic dysplasia of the upper extremities associated with other abnormalities: a new syndrome? AB - A 3-year-old Algerian boy with unusual facies, mesomelic dysplasia of the upper extremities, meta-epiphyseal changes in the lower extremities and skin dimples is reported. The authors are not able to classify the child's syndrome nosologically. PMID- 8516029 TI - A case of Kearns-Sayre syndrome with metaphyseal dysplasia. AB - A case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome) demonstrating bilateral symmetric metaphyseal dysplasia is reported. This represents a new association with the syndrome. PMID- 8516031 TI - Schinzel-Giedion syndrome and congenital megacalyces. AB - The Schinzel-Giedion syndrome is a rare autosomal recessive condition with typical facies, skeletal manifestations and congenital hydronephrosis. We report an infant with characteristic findings who had bilateral congenital megacalyces. Congenital megacalyces is believed to be a developmental abnormality, occurs in other malformation syndromes and has not previously been described in the Schinzel-Giedion syndrome. PMID- 8516032 TI - Radiography of thoracic intravascular stents in children with congenital heart disease. AB - Seventeen balloon expandable stents were placed in thoracic vessels in eleven children with vascular stenoses related to congenital heart lesions. We describe the normal radiographic appearance of three types of balloon expandable stents implanted in pulmonary arteries, pulmonary veins, and the superior vena cava of these children as well as the appearance of the complications we encountered. Knowledge of the radiographic appearance of these devices is important as chest radiography is a primary method of follow-up in children with balloon expandable stents placed to treat stenoses of intrathoracic vessels related to congenital heart disease. PMID- 8516033 TI - Pulmonary artery sling and hypoplastic right lung: diagnostic appearances using MRI. AB - We present a patient with pulmonary artery sling in association with hypoplasia of the right lung and stenosis of the right pulmonary artery, in whom the diagnosis was confirmed by MRI. PMID- 8516034 TI - Bronchiectasis in children: assessment by CT. AB - The prevalence of bronchiectasis (BR), in general, is decreasing, yet the disease can produce significant morbidity in children. In the pediatric age group the classical investigation by bronchography implies general anaesthesia, thus carrying an additional risk of complications. CT has proved highly accurate in the diagnosis of BR in adults. It is also considered a reliable modality for the diagnosis of BR in children. This conclusion was reached by analysing the radiographic and the CT findings in 40 children with the clinical suspicion of BR in 25 of whom the CT examination was positive. Nine patients of this last group had bronchography as well. There was complete correlation in the diagnosis and location between the CT and the bronchographic findings. Thus, it seems that the occurrence of this disease is still high in the pediatric population in the appropriate clinical and radiological setting. The imaging evaluation of BR should include chest radiographs, computerized tomography and, if surgery is planned, bronchography as well. PMID- 8516035 TI - Paediatric thymoma: unusual occurrence in two siblings. AB - Invasive cystic thymoma is reported in two siblings (an 11-year-old girl and a 9 year-old boy) and the radiographic, CT and ultrasonographic features are described. The tumours were removed by thoracotomy. Familial thymic masses are reviewed, and the imaging differential diagnosis of cystic anterior mediastinal mass in a child is discussed. PMID- 8516036 TI - Sonographic appearance of Sertoli cell tumour: with pathologic correlation. AB - Sertoli cell tumor is a rare tumor of the testis, with a good prognosis following orchiectomy in the pediatric patient. Sonography of such a tumor in a 5-year-old boy revealed diffuse inhomogeneous increase in echogenicity in an enlarged left testicle. The increased echogenicity of the testicle reflected the dense collagenous matrix of the lesion. PMID- 8516037 TI - CT differentiation of large abdominal lymphangioma from ascites. AB - Abdominal lymphangiomas are uncommon benign tumors, usually presenting in early childhood as a palpable abdominal mass. Their sonographic and CT appearance has been well described, and usually consists of well-defined, thin-walled cysts which can be unilocular, or multiloculated, and may contain septations. Rarely, these cysts may be large enough to be confused with ascites on physical exam. We present such a case to emphasize the imaging features that may help in the differentiation between ascites and large mesenteric lymphangiomas. PMID- 8516039 TI - Transfusional hemosiderosis in sickle cell anemia: another cause of an echogenic pancreas. AB - We report four sickle cell anemia patients who have received multiple blood transfusions and have been non-compliant on Desferal chelation therapy. Abdominal ultrasonography demonstrated an echogenic pancreas in all four patients. Magnetic resonance imaging in three patients revealed decreased signal intensity in all sequences in the pancreas and liver. All four patients had marked iron deposition on liver biopsy. To our knowledge, increased echogenicity of the pancreas secondary to hemosiderosis (2 degrees hemochromatosis) in sickle cell patients has not been reported in the radiologic literature. PMID- 8516038 TI - Association of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease. Report of a family with review of literature. AB - The association of autosomal recessive polycystic kidney disease (ARPKD) with congential hepatic fibrosis (CHF) is well known; a rare occurrence is that of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease (ADPKD). We report a family with ADPKD in which congenital hepatic fibrosis with severe portal hypertension (PHT) presented in a 4-year-old girl; the kidneys were initially normal. Typical changes of autosomal dominant polycystic kidney disease developed in the next decade and were also found in the mother and sister (neither of whom had any evidence of portal hypertension). Severe variceal bleeding was treated by sclerotherapy and beta receptor blocade. PMID- 8516040 TI - Three-dimensional CT diagnosis of myositis ossificans of the sacrospinous ligament. AB - We present the case of a 4-year-old female with a complex fracture of the left hemipelvis who, on follow-up CT imaging, developed new ossific densities within the peripelvic soft tissues of the contralateral side. Three-dimensional surface reformations of the pelvis demonstrated myositis ossificans along the course of the right sacrospinous ligament, thus elucidating unsuspected ligamentous injury and implying prior instability. PMID- 8516041 TI - Fatigue fracture of the sacrum in a child. AB - Fatigue fractures involving the sacrum are extremely rare, and to our knowledge no occurrence of such a fracture in a child has been reported in the English language literature. These fractures may mimic primary bone tumours or infection, and it is important to make an accurate diagnosis so that unnecessary biopsy can be avoided. We report a fatigue fracture of the sacrum in an 11-year-old child following prolonged aerobic exercise. PMID- 8516042 TI - Voluntary habitual dislocation of the hip: sonographic diagnosis. AB - A case of voluntary habitual dislocation of the hip with sonographic diagnosis of the "vacuum phenomenon" is described. This was seen as a characteristic hyperechoic interface between the acetabular fossa and the dislocating femoral head. PMID- 8516043 TI - Hemimegalencephaly: early sonographic pattern. AB - The sonographic changes in a 30-day-old infant with hemimegalencephaly are reported and compared with the CT and MRI findings. Sonography demonstrated the characteristic anomaly of the white matter not shown until later by CT and MRI. PMID- 8516044 TI - Tuberculoma in the suprasellar cistern: possible CT--misinterpretation as aneurysm. AB - A patient with multiple intracranial tuberculomas mimicking aneurysms is reported. The diagnosis was established by CT during the treatment of tuberculous meningitis. Anti-tuberculous therapy was continued until the radiological resolution of the lesions. A discussion of previous reports on the non-operative treatment of intracranial tuberculomas is included. PMID- 8516045 TI - Lipoma of the corpus callosum in a neonate: sonographic evaluation. AB - Lipomas of the corpus callosum are benign neoplasms which are rarely diagnosed in pediatric patients. In infants they are congenital lesions consisting of collections of adipose tissue; their etiology is unclear. We describe a case of callosal lipoma discovered by sonography in a 2-day-old neonate. PMID- 8516046 TI - Wilson's disease: MRI demonstration of cavitations in basal ganglia and thalami. AB - An MRI study of a patient with Wilson's disease is described, showing bilateral hyperintensity of the basal ganglia and thalami on T2-weighted images. Multiple, small nodular hyperintensities were superimposed on these hyperintense regions which presumably represented cavitations secondary to the spongy degeneration that is one of the histopathological features of cerebral Wilson's disease. PMID- 8516047 TI - Congenital bronchoesophageal fistula in childhood. Case report and review of the literature. AB - A case of congenital bronchoesophageal fistula in a 9-month-old infant is presented. He had had repeated pulmonary infections since he was 2 months old. A barium swallow examination showed a communicating fistula between the mid esophagus and the posterior segmental bronchus of the right upper lobe. MRI clearly demonstrated the course of the fistula. PMID- 8516048 TI - MRI in seven cases of Rathke's cleft cyst in infants and children. AB - Seven MRI observations of presumed Rathke's cleft cysts in infants and children are reported. Age ranged between 6 months and 13 years. Size of the cysts ranged between 4 and 20 mm. While 3 small cysts were detected incidentally, 4 were large enough to cause symptoms secondary to compression of the pituitary gland and suprasellar components. The MRI appearance of the Rathke's cleft cysts varied according to their nature. MRI provides a major contribution to the diagnosis of these lesions; nevertheless, it often remains difficult to differentiate complex Rathke's cleft cysts from cystic craniopharyngiomas. The difficulties related to this differentiation are discussed. PMID- 8516049 TI - Colour Doppler imaging of the acute paediatric scrotum. AB - The differentiation of the causes of acute scrotal pathology by clinical means alone is prone to inaccuracy, resulting in inappropriate surgical exploration. Colour Doppler imaging (CDI) provides the facility to assess blood flow. Torsion of the testis impedes blood flow, whereas it is enhanced or normal in inflammatory pathology. We have investigated 40 cases of acute scrotal disease by means of CDI in which the radiologist performing the test was unaware of the preliminary clinical diagnosis. The clinical diagnostic accuracy was 60%, whereas the diagnostic accuracy of CDI was 82%. CDI provides an effective means of enhancing diagnostic accuracy. PMID- 8516050 TI - Sonographic demonstration of congenital adrenal hyperplasia in the neonate: the cerebriform pattern. AB - Sonographic examination of the adrenal glands of three newborns with congenital adrenal hyperplasia demonstrated a cerebriform pattern. This is introduced as a sonographic feature specific to the disease. This finding in patients with ambiguous genitalia should suggest the diagnosis even if the adrenals are not significantly enlarged, and should prompt appropriate biochemical analysis and treatment. PMID- 8516051 TI - Fibrodysplasia ossificans progressiva and synovial chondromatosis. AB - Two cases of an unusual association-fibrodysplasia ossificans progressiva and synovial chondromatosis-in non-related children are presented. This association does not seem coincidental and raises several questions about the pathogenesis. A genetic hypothesis related to G proteins is proposed. This is supported by the fact that such abnormalities have been demonstrated in pseudohypoparathyroidism and fibrous dysplasia; these diseases can also be associated with fibrodysplasia ossificans progressiva. PMID- 8516052 TI - Ultrasound of the gastroesophageal junction. AB - In 560 endoscopy examinations performed on infants with severe vomiting, no esophagitis was found without endoscopic herniation of the gastroesophageal junction. The length of the abdominal esophagus therefore appears fundamental in reflux studies. Sonography is one of few techniques able to define the abdominal esophagus in vivo, both in terms of its anatomy and as a functional structure. Accurate assessment of the sonographic canal requires careful measurement under strictly defined clinical conditions. Using such criteria, ultrasound has a better sensitivity than barium studies in detecting small herniations. In addition to the important length measurements of the abdominal esophagus, other morphological and functional data can also be acquired by ultrasound. PMID- 8516053 TI - The Avianca plane crash: an emergency medical system's response to pediatric survivors of the disaster. AB - OBJECTIVE: On January 25, 1990, a jetliner crashed on Long Island, New York. Twenty-two children survived the crash. The purpose of this study was to evaluate the emergency medical system's response to these pediatric survivors. METHODS: A questionnaire was sent to all local, acute care hospitals to determine their specific pediatric capabilities and to rank them as level I, II, or III pediatric centers; level I centers are tertiary care facilities. A second questionnaire was sent to all hospitals that received pediatric survivors to collect specific clinical information for each patient. Based on this clinical information a Pediatric Trauma Score (PTS) was assigned to each patient. Children with a PTS < or = 8 are considered to be at increased risk of trauma-related mortality. The assigned PTS was compared to the level of the pediatric center to which each patient was transported. RESULTS: Of 25 children on board the plane, 22 (88%) survived the crash; of 135 adults on board, 70 (52%) survived (chi 2 = 9.9, P = .002). Seven children had a PTs < or = 8; only 1 of these high-risk patients was transported directly to a level I pediatric center, and only 2 of the 5 high-risk children initially transported to level III facilities were transferred to higher level pediatric centers. CONCLUSIONS: Pediatric survivors were neither adequately triaged nor transported to appropriate facilities which could optimize their care. Possible explanations for this include: (1) unique features of the rescue operation, (2) limited pediatric training of prehospital personnel, and (3) deficiencies of the regional disaster plan. Emergency medical services systems and disaster plans can be made more responsive to children's needs by: (1) acknowledging that children have special needs requiring referral, (2) improving the training of prehospital personnel in pediatric emergency care, (3) classifying ill and injured children according to appropriate triage criteria, (4) recognizing existing tertiary care pediatric centers as the optimal location for the treatment of critically ill and injured children, and (5) designating these centers as the appropriate transport destination for critically ill and injured children. PMID- 8516054 TI - Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. AB - OBJECTIVE: Steroids are widely used in Thailand and other dengue-endemic countries to treat severe dengue shock syndrome. This study was designed to determine whether a single high dose of methylprednisolone will reduce mortality in children with dengue shock syndrome who did not respond to simple fluid and plasma replacement therapy. METHODS: A prospective, randomized, double-blind, controlled trial was conducted in two hospitals in Khon Kaen Thailand during June to September in 1987 and 1988. Sixty-three children with severe dengue shock syndrome were randomized into two groups; the first group received a single dose of methylprednisolone (30 mg/kg) and the second group received placebo. RESULTS: There was no significant difference in mortality between the two groups (P = .63). The mortality rate was 12.5% (4/32) in the steroid group and 12.9% (4/31) in the group that received placebo. The sequelae at 2 weeks among treatment and control survivors were not significantly different. These two groups were comparable in age, sex, severity of illness, and duration of shock at the outset of the study. The two treatment groups were similar in subsequent hospital course as determined by maximum and minimum hematocrit level and bleeding severity. The numbers of patients in each group who had liver failure and evidence of disseminated intravascular clotting defect were also comparable. Complications such as occurrence of fever after shock, pneumonia, convulsion, cardiac arrest, pulmonary hemorrhage, and positive hemoculture were not significantly different in the treatment and control groups. CONCLUSIONS: A single high dose of methylprednisolone does not reduce mortality in severe dengue shock syndrome which does not respond to conventional critical care. PMID- 8516055 TI - Use of videotaping to evaluate pediatric resident performance of health supervision examinations of infants. AB - STUDY OBJECTIVES: To demonstrate reliability of a method for evaluating pediatric resident performance of health supervision examinations of infants using real patients and to evaluate pediatric resident performance of health supervision examinations of infants before and after an educational intervention consisting of a 6-month ambulatory rotation combined with video-assisted review of resident performance of the examination. DESIGN: Longitudinal cohort study in which all second-year residents were enrolled. Residents' preintervention (baseline) videotapes were compared with postintervention videotapes. Each resident served as his or her own control. SETTING: University hospital pediatric resident continuity clinic. SUBJECTS: Sixteen second-year pediatric residents who were participating in a required 6-month ambulatory rotation. METHOD AND MAIN RESULTS: Reliability study: Using a 51-item instrument derived from the American Academy of Pediatrics Guidelines for Health Supervision, trained raters blind to the sequence and dates of the videotaped health supervision examinations independently rated 44 resident encounters (a minimum of two raters per tape) and achieved good interrater reliability (kappa = 0.80). Intervention study: After a 6-month ambulatory rotation which included resident-faculty reviews of preintervention videotapes, residents showed a 14% mean improvement in performance scores for the examination (P < .05). CONCLUSIONS: The results indicate that videotaped health supervision examinations using real patients can be reliably evaluated by observational techniques in a continuity practice. A 6 month ambulatory block rotation coupled with video-assisted interactive review of examinations is associated with measurable improvement in resident performance on the postintervention test. PMID- 8516056 TI - Falls from heights: a problem not just in the northeast. AB - BACKGROUND: Falls from windows and balconies have long been recognized as a health hazard facing children in large, eastern cities. No study has explored this problem in western and sunbelt states. METHODS: A retrospective chart review of children admitted to a large, west coast hospital for injuries sustained secondary to a fall from a building was conducted. The health care costs for injuries secondary to falls were estimated by reviewing Los Angeles County hospital discharge data over a 3-year period. Representative cities in western and sunbelt states were surveyed about their building code regulations for windows and balconies. RESULTS: Ninety-three children fell from windows and 58 from other structures (balconies, fire escapes, and roofs). The fall victims were more likely to be male (male-female ratio, 1.6:1), younger than 3 years old, and playing at the time of the fall. In more than 70% of the cases reviewed, the child fell from a second-story window. Morbidity was significant, with two thirds of children experiencing at least one fracture and more than 30% of the children requiring the intensive care unit. The mortality rate was low (0.7%); however, 10% were left neurologically impaired. The cost for hospitalization was approximately $5000 to $8000 per child. The survey revealed a lack of building code regulations for windows or window guards in western and sunbelt states. CONCLUSIONS: Falls from windows are a significant problem for children, not only in eastern cities, but throughout the nation. Morbidity is significant, even from less than three stories, and the health care cost is high. Preventive strategies are suboptimal. PMID- 8516057 TI - Falling out of bed: a relatively benign occurrence. AB - OBJECTIVE: To determine the likelihood of injuries occurring to infants and children who fall out of bed. METHODS: A review of hospital records where children were documented to have fallen from a crib or bed and where the children were immediately assessed and examined following the fall. PATIENTS: Two hundred seven children younger than 6 years of age. One hundred twenty-four falls were from cribs and 83 from beds. The heights of the falls were 25 inches from beds or 41 inches when the child climbed over the bed rails and then fell, and 32 inches from cribs or 54 inches for those who fell after climbing the crib rails. RESULTS: There were 29 superficial injuries such as contusions or minor lacerations. One simple skull fracture was noted incidentally on skull roentgenogram and there was one fractured clavicle. There were no serious, multiple, visceral, or life-threatening injuries. Calculation of the momentum of impact between the injured and noninjured showed no significant difference. CONCLUSIONS: Because falls from short distances are unlikely to produce serious injury, the reliability of the history should be questioned when a child has significant injuries said to have resulted from a short fall. PMID- 8516058 TI - Early initiation of sex and its lack of association with risk behaviors among adolescent African-Americans. AB - OBJECTIVE: High rates of adolescent homicide, pregnancy, substance abuse, and sexually transmitted diseases underscore the importance of interventions designed to reduce problem behaviors. However, the definition of "problem" behavior and the association with other activities may change between youth cultures. Therefore, greater attention to defining the "problem" behaviors to be targeted will permit more effective utilization of primary vs secondary intervention strategies and identification of high-risk individuals. DESIGN: Two studies of African-American adolescents regarding sexual intercourse, school truancy, substance abuse, and drug trafficking are presented. The first study involved 57 youths (10 to 14 years of age) from a pediatric primary health center and gathered data through pile-sorting. The second study of 300 youths (9 to 15 years of age) from six public housing sites used a questionnaire administered by a "talking" computer. Both studies assessed different self-reported behaviors, feelings about engaging in specific behaviors, and perceptions of friends' behaviors. RESULTS: While 40% of subjects reported having had sex, substantially smaller proportions reported school truancy (14%), illicit drug use (2% to 6%), or drug trafficking (6%). Analyses of reported behaviors, feelings, and perceived peer norms revealed that sex was consistently depicted as forming a different domain from other problem behaviors. CONCLUSIONS: Interventions that rely on primary prevention strategies for sexual intercourse and that identify sexually active youths as at risk for problem behaviors may not be appropriate for African American adolescents growing up in resource-depleted urban areas. PMID- 8516059 TI - Surfactant therapy in full-term neonates with severe respiratory failure. AB - OBJECTIVE: In light of the paucity of published data on the use of surfactant in full-term infants with respiratory failure due to meconium aspiration syndrome and respiratory distress syndrome, we report our experience with this therapy. Our goal was to explore possible justification for randomized controlled trials of surfactant treatment in similar patients at an earlier, less severe stage of the disease. METHODS: Retrospective consecutive case series of 20 infants with severe meconium aspiration syndrome and 29 infants with severe respiratory distress syndrome who received bovine surfactant between March 1990 and December 1992 in three neonatal intensive care units in a regionalized setting. Outcome of treatment was assessed by comparing changes in several respiratory indices including the oxygenation index, between 4 and 6 hours and 1 and 3 hours before and after the first dose of surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. RESULTS: In the meconium aspiration group the mean oxygenation index decreased from 36 +/- 12 at 1 to 3 hours presurfactant to 24 +/- 14 at 1 to 3 hours postsurfactant (P < .001). In the patients with respiratory distress syndrome the mean oxygenation index fell from 30 +/- 17 at 1 to 3 hours presurfactant to 12 +/ 6 at 1 to 3 hours postsurfactant (P = .0001). Three of 20 patients with meconium aspiration syndrome and 3 of 29 patients with respiratory distress syndrome received extracorporeal membrane oxygenation. CONCLUSIONS: Surfactant therapy in full-term infants with respiratory failure due to the meconium aspiration and respiratory distress syndromes is often effective in improving gas exchange. A randomized controlled trial of surfactant therapy at an earlier stage in the course of the illness should be performed. PMID- 8516060 TI - Effect of antibiotic therapy and etiologic microorganism on the risk of bacterial meningitis in children with occult bacteremia. AB - OBJECTIVE: To quantify the effect of antibiotic therapy on the probability of subsequent bacterial meningitis in children with fever without source treated as outpatients. DESIGN: Bayesian meta-analyses. REPORTS INCLUDED: All reports of the organism-specific prevalence of occult bacteremia in children with fever without source treated as outpatients, and the organism-specific prevalence of subsequent meningitis in children with occult bacteremia initially treated as outpatients stratified by type of antibiotic therapy. RESULTS: The mean probabilities of subsequent meningitis in children with occult bacteremia were 9.8%, 8.2%, and 0.3% in the no antibiotic, oral antibiotic, and parenteral antibiotic therapy groups, respectively. All cases of bacterial meningitis in children with occult bacteremia treated with oral antibiotics were due to Haemophilus influenzae. There were no cases of culture-positive bacterial meningitis in 139 bacteremic children treated with ceftriaxone (mean probability, 0.3%; 95% confidence interval, 0.0% to 1.5%). The mean probabilities of bacterial meningitis in a child with fever without source treated as an outpatient without antibiotics were: Streptococcus pneumoniae, 0.21%; and H influenzae, 0.06%. CONCLUSIONS: Antibiotic therapy is effective in preventing meningitis in children at risk of occult bacteremia. PMID- 8516061 TI - Stepping up the treatment of children with asthma. PMID- 8516062 TI - "Home alone": potential implications for adolescents. PMID- 8516063 TI - Surfactant replacement therapy: prophylaxis or treatment? PMID- 8516064 TI - Infant botulism at 1 week of age: report of two cases. PMID- 8516065 TI - Discontinuation of breast-feeding infrequent among jaundiced neonates treated at home. PMID- 8516066 TI - Prevalence of undetected tinea capitis in household members of children with disease. PMID- 8516067 TI - Bronchiolitis obliterans: a complication of group B streptococcal disease treated with extracorporeal membrane oxygenation. PMID- 8516068 TI - Blue rubber bleb nevus syndrome: case report and review of the literature. PMID- 8516069 TI - American Academy of Pediatrics, Committee on Children With Disabilities. Pediatric services for infants and children with special health care needs. PMID- 8516070 TI - Guidelines and levels of care for pediatric intensive care units. Committee on Hospital Care of the American Academy of Pediatrics and Pediatric Section of the Society of Critical Care Medicine. PMID- 8516071 TI - American Academy of Pediatrics Committee on Environmental Health: Lead poisoning: from screening to primary prevention. PMID- 8516072 TI - More to be learned from Crigler-Najjar patients. PMID- 8516073 TI - Hepatitis B immunization. PMID- 8516074 TI - Preoperative coagulation screening in children. PMID- 8516075 TI - Hypoxaemia in infants with bronchopulmonary dysplasia. PMID- 8516076 TI - Parents often urge overtreatment. PMID- 8516077 TI - Movies, guns, and kids. PMID- 8516078 TI - Clinical trials and P values. PMID- 8516079 TI - Use of retinoids for pediatric dermatologic disorders. PMID- 8516080 TI - Appointment-keeping behavior in adolescents: factors associated with follow-up appointment-keeping. AB - STUDY OBJECTIVES: To identify the sociodemographic and Health Belief Model predictors of follow-up appointment-keeping behavior. DESIGN: Prospective observational study. SETTINGS: General adolescent medical clinic. PATIENTS AND MEASUREMENTS: Sequential sample of 166 adolescents (aged 12 to 20 years, mean = 15.9 years) enrolled in the clinic. The population was 75% female; the racial ethnic distribution of the sample was 37.9% black, 29.8% white, 11.2% Asian, 14.3% Hispanic, and 6.8% "other" background. Subjects' social class was primarily lower-middle (60.5%) and middle class (28.6%). A subsample was randomly assigned to be interviewed about their beliefs concerning their follow-up appointment and the constructs of the Health Belief Model. RESULTS: Forty-eight percent of the total sample failed to keep their follow-up appointment. There was a significant positive correlation between social class and appointment keeping (F = 5.07; df = 5,110; P = .026). Neither race-ethnicity nor who made the appointment were found to be associated with follow-up appointment-keeping. The only construct of the Health Belief Model found to be significantly associated with appointment keeping was the number of potential negative outcomes resulting from noncompliance perceived by the subject (F = 6.85; df = 1.74; P = .011). CONCLUSIONS: Clinicians must work with adolescents to improve their understanding of the potential negative outcomes associated with noncompliance to improve appointment-keeping behavior. PMID- 8516081 TI - Adolescents' risky behavior and mass media use. AB - OBJECTIVE: To understand better the relationship between adolescents' use of the mass media (including television, radio, and magazines) and their risky or unhealthy behaviors. DESIGN: Secondary data analysis of a 1987 in-home survey of 2760 randomly selected 14- to 16-year-old adolescents in 10 urban areas in the southeastern United States. MEASUREMENT: The extent of participation in eight potentially risky behaviors (sexual intercourse, drinking, smoking cigarettes, smoking marijuana, cheating, stealing, cutting class, and driving a car without permission) and the use of a variety of mass media. RESULTS: Adolescents who had engaged in more risky behaviors listened to radio and watched music videos and movies on television more frequently than those who had engaged in fewer risky behaviors, regardless of race, gender, or parents' education. White male adolescents who reported engaging in five or more risky behaviors were most likely to name a heavy metal music group as their favorite. Adolescents reported reading a wide diversity of magazines, and most reported reading at least one of a few selected magazines. Sports and music magazines were most likely to be read by adolescents who had engaged in many risky behaviors. CONCLUSIONS: Mass media health promotion efforts could more specifically target adolescents who are engaging in multiple risky behaviors. PMID- 8516082 TI - Relationship between after-school care of adolescents and substance use, risk taking, depressed mood, and academic achievement. AB - OBJECTIVE: To examine the relationship between parental monitoring and six negative behaviors: cigarette, alcohol, and marijuana use; depressed mood; risk taking; and lower academic grades. DESIGN: Survey of 3993 ninth-grade students in six school districts in southern California. SUBJECTS: The sample consisted of 1930 boys and 2063 girls, self-classified as non-Hispanic white (32%), African American (13%), Hispanic (46%), or Asian (9%). RESULTS: A relationship was found between unsupervised care after school and susceptibility to cigarette, alcohol, and marijuana use; depressed mood; risk taking; and lower academic grades. Adolescents who were unsupervised at home were slightly more likely to engage in problem behavior than those who were supervised at home. Adolescents at a neighbor's house, at school, or at a job and especially those who "hang out" were most likely to engage in problem behavior. Risk was higher if the parent had an unengaged parenting style. Although girls were less likely than boys to engage in problem behavior when supervised, as supervision decreased they were significantly more likely to have each of these problems. Family structure had little impact on risk. CONCLUSIONS: Self-care, especially when it occurs outside of the home, is associated with substance use, risk taking, depressed mood, and lower academic grades. PMID- 8516083 TI - Antineuronal antibodies in movement disorders. AB - OBJECTIVE: To determine whether children with recent onset of movement disorders (Tourette syndrome, motor and/or vocal tics, chorea, choreiform movements) show evidence of serological antibodies directed against the human central nervous system as previously documented in research on Sydenham's chorea. METHODS: Serum antibodies against previously frozen human caudate nucleus sections were analyzed using a blinded design and immunofluorescent staining methods. The sera of one group of 50 children referred for evaluation of attention deficit hyperactivity disorder, behavior disorders, and learning disabilities (24 with an associated movement disorder) seen between June 1989 and June 1990 were analyzed. The study was replicated in 33 children (21 with an associated movement disorder) seen between June 1990 and November 1990. RESULTS: In the original sample of 50 children, those with movement disorders were significantly more likely to have evidence of antineuronal antibodies than were those without movement disorders (odds ratio [OR] 4.80, 95% confidence interval [CI] 2.58 to 8.93). Results of the replication were similar (OR 6.00, 95% CI 2.56 to 14.03). For the total group, the OR was 5.50, (95% CI 3.54 to 8.99), which is highly significant. The percentage of children with a movement disorder whose sera were strongly positive for antineuronal antibodies (44%) was very similar to that previously found in children with Sydenham's chorea (46%). Children with movement disorders were also more likely than children without movement disorders to have at least one antistreptococcal titer elevated. CONCLUSIONS: The data strongly suggest an association between antecedent group A beta-hemolytic streptococcal infection as inferred from elevated antistreptococcal titers and the presence of serum antineuronal antibodies, which may, in turn, be linked to childhood movement disorders. PMID- 8516084 TI - Infant health care utilization predicted by pattern of prenatal care. AB - STUDY OBJECTIVE: The objective of this study was to examine the relationship between patterns of prenatal care and subsequent infant health care use in a sample of inner-city women and their infants. In testing this relationship we controlled for several sociodemographic, economic, and psychological factors. DESIGN: This case-control study examined medical records of 148 infants born to mothers previously enrolled in a 9-month study of prenatal care and use or nonuse of illicit drugs. Cases (N = 62) were defined as infants born to women who first registered for prenatal care after 28 weeks' gestation or completed fewer than four prenatal visits. Controls (N = 86) were all other infants matched by date of birth. Data on maternal health and sociodemographic factors were obtained from a maternal interview and medical record review. Maternal drug use was defined as the use of illicit drugs at any time during the pregnancy based on maternal interview and/or a positive maternal or neonatal urine toxicology screen obtained within 48 hours of delivery. RESULTS: Infants of case mothers had significantly lower birth weight and gestational age, increased number of protective service referrals, and lower completion rate of three or more health supervision visits by 9 months of age. Multiple logistic regression analysis revealed that adequate prenatal care was significantly associated with adequate use of infant health care independent of maternal drug use, educational level, marital status, and number of previous living children. CONCLUSIONS: Patterns of infant health care use can be predicted before birth based on the mother's pattern of prenatal care use. PMID- 8516085 TI - Cerebrospinal fluid monoamine precursors and metabolites in human neonates following in utero cocaine exposure: a preliminary study. AB - BACKGROUND: Cocaine acts in the central nervous system by increasing dopamine release and inhibiting the reuptake of dopamine and other monoaminergic neurotransmitters. Prenatal cocaine exposure may cause neurochemical changes in developing monoaminergic neurons and might alter brain structure and function. No data have been published on central nervous system monoamine precursors and metabolites in human neonates exposed prenatally to cocaine. METHODS: Cerebrospinal fluid (CSF) was obtained from neonates undergoing lumbar puncture to rule out infection. The CSF was analyzed for the neurotransmitter precursors and metabolites tryptophan, tyrosine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid. Drug exposure was ascertained by medical record review and urine and meconium assays. RESULTS: Eleven neonates were cocaine-exposed, based on positive meconium or urine assays for benzoylecgonine; 20 were unexposed, based on both negative history and assay. The exposed and unexposed groups did not differ significantly in gender, perinatal stress, clinical illness, or exposure to other illicit drugs, but did differ in mean gestational age, growth parameters, and exposure to cigarettes. Cocaine exposed neonates had significantly lower levels of CSF homovanillic acid (mean 148.1 vs 218.5 ng/mL, P = .01). The magnitude of this difference was similar after correcting for each of four potential confounding factors, although no longer statistically significant in all cases (P values ranged from .044 to .17). No significant differences were observed for tyrosine, tryptophan, 5 hydroxyindoleacetic acid, or 3-methoxy-4-hydroxyphenylglycol. CONCLUSIONS: These preliminary results suggest an association between prenatal cocaine exposure and decreased CSF homovanillic acid, the principal metabolite of dopamine. Prenatal cocaine exposure may result in changes in central dopaminergic systems in the human neonate. PMID- 8516086 TI - Population-based study of fall injuries in children and adolescents resulting in hospitalization or death. AB - OBJECTIVE: To determine the incidence and characteristics of fall-related injuries to children and adolescents. DESIGN: Population-based study. SETTING: All hospital discharges in Washington State for fall-related injuries in 1989 and 1990. POPULATION: Children and adolescents 19 years and younger. RESULTS: Falls accounted for nearly one third of all trauma admissions, and fall patients tended to be younger than those with other injuries. Falls from one level to another accounted for 40% of the total. One fourth of all patients and 42% of preschoolers sustained head injury. The annual cost of these injuries in Washington State was $4.5 million. PMID- 8516087 TI - Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. AB - OBJECTIVE: To compare the benefits and adverse reactions of theophylline and beclomethasone (BDP) in the long-term control of mild to moderate chronic asthma in children. DESIGN: Multicentered, double-blind, double-placebo, randomized, controlled trial. PATIENTS: One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma. INTERVENTION: Treatment with either BDP, 84 micrograms four times a day, or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms. MAIN OUTCOME MEASURES: Daily diary record of symptoms, peak flow rates, supplemental bronchodilator and glucocorticoid treatment, doctor and hospital visits, absence from work and school, and side effects. RESULTS: Aerosol BDP and sustained release theophylline were effective primary treatments for mild to moderate chronic asthma. Beclomethasone resulted in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline. Side effects were observed significantly more frequently with theophylline than with BDP. Growth velocity suppression was noted with BDP and was more pronounced in boys. Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation. CONCLUSION: Both theophylline and BDP are effective therapy for mild to moderate asthma. Caution must be used with the administration of BDP in children because of possible growth velocity suppression. PMID- 8516088 TI - Niacin treatment of hypercholesterolemia in children. AB - OBJECTIVE: To determine the efficacy and adverse effects of niacin treatment of hypercholesterolemia in children. DESIGN: Retrospective review. SETTING: Two university hospital referral clinics. PATIENTS: All children who received single drug niacin treatment for severe hypercholesterolemia between 1980 and 1991. RESULTS: Twenty-one children, aged 4 to 14 years, were treated with niacin, 500 to 2250 mg daily. Pretreatment total serum cholesterol value (mean +/- SD) was 7.84 +/- 1.14 mmol/L (303 +/- 44 mg/dL), and low-density lipoprotein cholesterol value was 6.28 +/- 1.16 mmol/L (243 +/- 45 mg/dL). Niacin treatment in daily doses > 1000 mg reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30% (P < .001) but had no effect on high-density lipoprotein cholesterol and triglycerides. As in adults, reversible adverse effects were common, occurring in 16 (76%) of the 21 children. Six children (29%) had reversible dose-related elevations of serum aminotransferase levels. Niacin therapy was discontinued in 8 children (38%) because of flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels. CONCLUSIONS: This study suggests that although niacin treatment in children is efficacious, adverse effects are common. Until further study demonstrates long-term safety, niacin treatment should be reserved for the closely-supervised treatment of severe hypercholesterolemia by a lipid specialist. PMID- 8516089 TI - Malaria in children in Chicago. AB - OBJECTIVE: To review the experience of a large children's hospital and two community hospitals in Chicago in which malaria was diagnosed in children during a recent 6-year period. METHODS: Retrospective medical record review covering the years 1985 to 1990. RESULTS: Twenty cases of childhood malaria were diagnosed, generally in patients hospitalized for fever unresponsive to oral antibiotics also associated with splenomegaly, with presumptive diagnoses of malignancy, typhoid fever, acute appendicitis, or urinary tract infection. History of recent immigration to the United States or travel to a malaria-endemic area was frequently not elicited until several days into hospitalization, thus delaying diagnosis and therapy. CONCLUSIONS: Because malaria in the United States pediatric population has increased as a result of foreign immigration and overseas travel, pediatricians must be alert to the possibility of malaria in febrile children, and the importance of antimalarial prophylaxis should be communicated to parents of children traveling to endemic areas. PMID- 8516090 TI - Superiority of oral agar and phototherapy combination in the treatment of neonatal hyperbilirubinemia. AB - OBJECTIVE: To determine the value of oral agar in the treatment of neonatal hyperbilirubinemia and to compare it with two other treatment modalities: phototherapy alone and phototherapy plus oral agar. METHODS: Two hundred eight jaundiced full-term newborns were divided into four groups. They were given either phototherapy alone, phototherapy plus oral agar, oral agar alone, or no treatment (control group). The changes in the serum bilirubin values were determined and the results were compared statistically, mainly using analysis of variance. RESULTS: In all three therapy groups, the time required to reduce the bilirubin level to either 15 mg/dL or to 10 mg/dL was significantly shorter than that required by the control group. Although oral agar was found to be as effective as phototherapy, the most significant decrease in bilirubin level was in the combination group. CONCLUSIONS: The efficacy of phototherapy in decreasing the serum bilirubin level in neonatal hyperbilirubinemia can be augmented with the use of oral agar. Oral agar can also be used as a single agent for the treatment of neonatal hyperbilirubinemia, since it is as effective as phototherapy. PMID- 8516091 TI - Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation. AB - OBJECTIVE: Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age. DESIGN: One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed. RESULTS: Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup. PMID- 8516092 TI - Cerebral oxygen metabolism in newborns. AB - OBJECTIVE: A better understanding of the developmental changes in brain energy metabolism that occur in human neonates is critically important for designing rational treatment strategies that ensure an adequate supply of nutrients to the brain and minimize deleterious side effects of therapeutic interventions in sick newborns. METHODS: Cerebral metabolic rate for oxygen (CMRO2) was measured with positron emission tomography in 11 sick newborns of different gestational ages. RESULTS: In five preterm infants, mean hemispheric CMRO2 was 0.06 to 0.54 mL 100 g-1 min-1. Two of these preterm infants with virtually absent CMRO2 (0.06 mL 100 g-1 min-1) had minimal or no evidence of parenchymal brain injury detected in the newborn period. In six term infants, mean hemispheric CMRO2 was 0.0 to 1.3 mL 100 g-1 min-1. Two with no neurological disease had mean hemispheric CMRO2 of 0.4 and 0.7 mL 100 g-1 min-1 and were normal at 6 and 7 months, respectively. CONCLUSIONS: CMRO2 in four newborns who had minimal or no detectable brain injury was considerably below the threshold for brain viability in adults of 1.3 mL 100 g-1 min-1. This indicates that energy requirements in fetal and newborn brain are minimal or can be met by nonoxidative metabolism. PMID- 8516093 TI - A beginning theory of personal space boundaries. AB - The author claims that boundaries function as a filtering device to protect the individual from environmental overload and consequent disorganization. She describes the importance of boundary restoration, maintenance, and promotion in nurses and their clients. She then relates the concept of boundaries to other pertinent concepts and introduces a beginning theory of personal space boundaries. PMID- 8516094 TI - Dance movement: a therapeutic program for psychiatric clients. AB - Findings from a research project on the effectiveness of dance movement with psychiatric clients are reported in this article. The author discusses how dance movement therapy (DMT) improves the emotional, psychological, and physical well being of psychiatric clients. She then discusses the ways in which expressive and communicative behaviors were used as nursing interventions to facilitate higher levels of wellness. PMID- 8516095 TI - Self-reported sexual behaviors of schizophrenic clients and noninstitutionalized adults. AB - In this descriptive study the authors compare self-reported sexual behaviors of a group of hospitalized psychiatric clients with a group of noninstitutionalized adults. An interview method was used to obtain information about interest in sex, frequency of intercourse, and sexual satisfaction. Control group members and clients reported about the same interest in sex, frequency of intercourse, and satisfaction in their younger years. In their current lives, however, clients reported slightly less sexual feeling and a much lower frequency of intercourse. Nearly half of the clients were not having intercourse, with the majority of those attributing the reason as hospitalization. Concerns about normalizing the institutional environment for sexual expression for chronically mentally ill persons are discussed. PMID- 8516096 TI - Sleep automatism: clinical study in forensic nursing. AB - The authors describe sleep automatism as it pertains to forensic nursing. A plea of sane automatism may result in an acquittal and, as a defense, creates a very interesting medical legal circumstance. A case study is presented to illustrate the necessity for nursing to know how to assess for this dissociative state, to understand the legal implications, and to identify nursing issues relevant to sleep automatism defenses. The clinical and personality characteristics on which evaluations should be based are also outlined. PMID- 8516097 TI - The discursive constitution of nursing education: exploring the discursive context of problem-solving. PMID- 8516098 TI - Diverse thinking styles of nurses. PMID- 8516099 TI - Rethinking clinical judgment. AB - In this paper, I've attempted to explicate ways in which the cognitive models rooted in the rational tradition have dominated our thinking about clinical judgment in nursing--both in framing research into so-called "cognitive processes" and in shaping our educational practices. Using exemplars from a study of clinical expertise in nursing, I have described several aspects of clinical judgment which cannot be accounted for by the cognitive models. I've highlighted assumptions underlying our educational practices which are challenged by our new understanding of clinical judgment and offered one illustration of an alternative approach to teaching which may be relevant for RN education. PMID- 8516100 TI - RN-BSN curriculum development: a dynamic, student-centered approach. AB - A student-centered curriculum is possible to design which does not compromise quality. However, the mechanics of creating and operationalizing such a program are a complex matter and require the ongoing support, assistance, and involved commitment of everyone involved under the broad umbrella of curriculum. Given the highly specific learning needs of RRNs, a student-centered curriculum is most easily implemented in an RN only program, where each element of the curriculum can be tailored expressly to match learning style. RRNs describing the attributes of RN only designed programs cite the support of independence that is the hallmark of such programs. For these reasons, RN only programs best address the needs of adult learners. PMID- 8516101 TI - Twenty years of success and still growing. PMID- 8516102 TI - Factors influencing the retention and progression of students in an RN-MS program. PMID- 8516103 TI - Evaluating the academic experience for returning registered nurses. PMID- 8516104 TI - Women's ways of knowing and teaching RN students. PMID- 8516105 TI - Innovations in registered nurse education: from oppression to empowerment. PMID- 8516106 TI - When it all comes together: the elements of a successful clinical experience. PMID- 8516107 TI - A profile of preceptorships in baccalaureate degree nursing programs for registered nurses. PMID- 8516108 TI - RN students need to tell their stories. AB - Finally, what is it about RN students' experiences in the transition process in nursing education that makes their stories need to be told? Actually this question is asked from both the side of the RN students who are the learners and need to tell the stories, and the side of the educator/advisor who needs to have the stories told. In short, the answer to both is that these stories reveal very graphically and meaningfully what is happening in the learning and professional development processes and, simultaneously, they facilitate the progression of those processes. The RN students seem to have an innate sense about what telling their stories will do for them in relation to their learning and professional development processes. They require very little encouragement to prompt their story telling. For the educators/advisors, no other strategy is as adaptable and achieves as much in relation to facilitating the learning and development processes. For both parties, the graphic revelations in stories paint a picture of how past, present, and future blend together to form a meaningful, coherent view of a position in the world. According to Antonovsky's (1979) work on stress and coping, such a view is necessary if stress is to be resisted and health maintained.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8516109 TI - Transforming RN education: clinical learning and clinical knowledge development. AB - Transforming RN education has the potential for transforming clinical teaching and learning for all students. The returning RN student offers possibilities for clinical learning that the generic student does not have, but this should not cause us to limit the returning RN student to the generic level. Where possible innovative programs should be developed to move the RN student from baccalaureate level to the Master's level. As educators, we should take the opportunity to increase the numbers of nurses who are educationally prepared to move into advanced levels of practice. The returning RN student offers a rich human resource for the profession, and a rich resource for improving our clinical teaching as well as our practice. PMID- 8516110 TI - The teacher-student relationship: the heart of nursing education. AB - This author has witnessed many nurses entering the university unhappy, feeling an outside pressure (e.g., the nursing profession) rather than a personal need, to do so. Nurses return to school often at great personal expense, adding one more role to an already full family and work life. Most nurses study part-time, and do not necessarily have the support of their peers in the workplace as they embark on this journey. A tradition of expecting authority, and a technical training background are added to the factors that create a profile which is not atypical of a returning-to-school nurse. Assisting these nurses to continue to grow and to flourish as nurses, as learners, and as persons involves a reframing of the process and the products of learning. Teaching must become a process of evoking possibilities and meaning for the individual student, while validating and using the richness of the experience that the student brings to the setting. PMID- 8516111 TI - Distance education for RN students. PMID- 8516112 TI - The RN mentor program: an exercise in leadership. PMID- 8516113 TI - Transforming RN education: new approaches to innovation. PMID- 8516114 TI - Ideological barriers to nursing education for returning RN students. PMID- 8516115 TI - Review of research related to educational re-entry for the registered nurse: 1985 1991. PMID- 8516116 TI - "Harbingers of entry into practice": the lived experience of returning RN students. PMID- 8516117 TI - Privatisation by the side door? PMID- 8516118 TI - Tap-dancing to health. PMID- 8516119 TI - Under fire. PMID- 8516120 TI - Teen aid. PMID- 8516121 TI - Mature ideals. PMID- 8516122 TI - Challenging assumptions. PMID- 8516123 TI - Improving awareness. PMID- 8516124 TI - Making sense of pressure sore prediction calculators. PMID- 8516125 TI - Looking after Gemma. PMID- 8516126 TI - Paying the piper. PMID- 8516128 TI - A vision for all to see. PMID- 8516127 TI - A space to move in. PMID- 8516129 TI - Corporate preparation. PMID- 8516130 TI - A model for the future. PMID- 8516131 TI - Invisible visitors. PMID- 8516132 TI - How do colleges approach AIDS/HIV? PMID- 8516134 TI - Making a fresh start. PMID- 8516133 TI - An alternative to seclusion? PMID- 8516135 TI - Special solutions. PMID- 8516136 TI - Staff 'just missed routine AIDS tests'. PMID- 8516137 TI - Students 'too scared to reveal they have HIV'. PMID- 8516138 TI - Drawing the line. PMID- 8516139 TI - Fighting back. PMID- 8516140 TI - After Allitt. PMID- 8516141 TI - Bottomley bobs back. PMID- 8516142 TI - Building blocks. PMID- 8516143 TI - The mechanics of eating and drinking. PMID- 8516145 TI - New commitments. PMID- 8516144 TI - Good intentions. PMID- 8516146 TI - Culture shock. PMID- 8516148 TI - Witness. Interview by Daloni Carlisle. PMID- 8516147 TI - What makes a person? PMID- 8516149 TI - Community care. A smooth path home. PMID- 8516150 TI - Perceptions and practice of health education and heath promotion in acute ward settings. AB - This paper reports on an overview of the findings from a two-year Department of Health-funded research project. The study had two overall aims: to describe the extent to which health education and health promotion had become integrated into nurses' practice in acute-care settings and to identify the facilitative and inhibitory factors involved. The study comprised separate sequential stages of data collection and utilised a multi-method approach. Findings from a survey of ward sisters and from ward-based case studies are presented and discussed. These suggest that nurses have yet to fulfill their potential as educators and promoters of health and that a number of influences interact at ward level to encourage or impede the development of this role. PMID- 8516151 TI - Wash and wear. PMID- 8516152 TI - Underpad overview. PMID- 8516153 TI - UKCC policy on AIDS 'must be scrapped'. PMID- 8516154 TI - Allitt case highlights mental health needs of many staff. PMID- 8516155 TI - The enemy within. PMID- 8516156 TI - Age-old problem. PMID- 8516158 TI - The price is wrong. PMID- 8516157 TI - The fight to go public. PMID- 8516159 TI - Mother's choice. PMID- 8516160 TI - Refreshing research. PMID- 8516161 TI - Violence at work--at risk of assault. PMID- 8516162 TI - Work injuries. Victim support. Violence at work. PMID- 8516163 TI - HIV/AIDS. Mind body and soul. PMID- 8516164 TI - Staff nurses--high hopes. PMID- 8516165 TI - Midwifery--continuous assessment. PMID- 8516166 TI - Diabetes mellitus--balancing act. PMID- 8516167 TI - Systems of life. The eye and vision. 1. PMID- 8516168 TI - Midwives' attitudes to clients of Asian descent. PMID- 8516170 TI - District nursing. Support for carers. PMID- 8516169 TI - District nursing. Healthy practice. PMID- 8516171 TI - Peer pressure threatens HIV precautions. PMID- 8516172 TI - Issues and challenges in clinical nursing research. AB - In this article, issues encountered that are problematic in conducting research in clinical settings are discussed along with potential solutions. Subject accrual, compatibility of the research protocol with day-to-day operation of the clinical site, gaining cooperation from groups of health professionals, and obtaining required approvals are the most common problems encountered. Overcoming these problems does not mean the elimination of them; awareness and acknowledgement of these problems in the planning process will minimize the negative influence they may have on the study. PMID- 8516173 TI - Management of preterm labor and prevention of premature delivery. AB - Preterm births continue to be the leading cause of perinatal mortality despite efforts to prevent preterm labor. Tocolytic therapy with beta-mimetic drugs was believed to be the solution for preterm labor, but the Canadian Preterm Labor Investigators Group recently reported that the use of ritodrine had no significant beneficial effect. Despite the various methods presently used for the management of preterm labor and prevention of premature delivery, the incidence of preterm birth remains unchanged. Health professionals must remain optimistic, however, and continue to investigate causes, whether they are social or medical, and to seek the unknown. Nursing personnel should play an important role in this area as health promoters and educators of patients. Nurses should also collaborate with other health professionals to determine effectiveness of therapy and the causes of preterm labor. For instance, this author is currently involved in a research project seeking barriers to prenatal care using a questionnaire and reviewing maternal records in order to determine length of labor and its relationship to subsequent preterm labors. The goals of the Year 2000 National Health Objective for low birth weight and infant mortality are not likely to be attained. Prematurity has gained national attention, however, and with public and professional awareness, perhaps this problem will decrease. PMID- 8516174 TI - Developmental care of low birth weight infants. AB - Nurses are the key to the implementation of developmentally focused care for LBW infants. There seems to be a sufficient research base to support reduced lighting in the hospital setting and consideration of cycled lighting. Face-to-face visual stimulation would seem sufficient for infants less than 40 weeks old until further research is done. In regard to sound, it seems clear that failure to reduce noise created by personnel, faculty equipment, radios, and so on represents negligence. Talking to infants who are in states other than sleep is to be encouraged, and planned interventions such as taped music and vocal selections need continued exploration. There seems to be a sufficient research base to support handling and caretaking that considers the state of the infant and aims to disrupt sleep as little as possible. Similarly, there appears to be ample support for placing infants in ways that promote a balance of flexion and extension or in the prone position whenever possible. NNS should be used during feeding and to reduce stress. Attention to reducing pain should be as much a part of the care of LBW infants as it is for adults. The potential negative effects of drugs on the developing brain must be considered and studied. Finally, the family, including siblings, should be encouraged to participate in the infant's plan of care as much as possible and prepared for discharge well in advance of the actual date. A note of caution should be entertained for stimulation programs not based on sufficient research. It is possible, perhaps even probable, that excessive sensory input at critical times can do harm. Interventions may be recommended with great enthusiasm but without research support. Thus, until the relative merits and possible adverse effects of various interventions are known, they should be approached with caution. Perhaps remembering that the first consideration in giving care is to "Do not harm" should facilitate our care of LBW infants. PMID- 8516175 TI - Physical and psychosocial nursing care for patients with HIV infection. AB - As suggested earlier we have chosen in this article to discuss only a small group of key physical and psychosocial concerns and needs associated with HIV and AIDS. These were the issues most frequently discussed by a study group of people living with HIV. We recognize, however, that holistic nursing intervention considers the totality of the individual living with HIV: body, mind, and spirit. It is to that end that the discussed nursing diagnoses and interventions are directed. Ultimately, the successful identification of and intervention in HIV related problems rests in the unique relationship between nurse and patient sharing as collaborators in the healing experience. The body of contemporary nursing and behavioral science research in the area of HIV/AIDS continues to grow. Presently the National Center for Nursing Research is supporting studies focusing on such areas as the use of designated versus general care settings for HIV patient care, quality of nursing care in HIV/AIDS, the effects of nurse-managed home care for AIDS patients, stress and coping in caregivers of AIDS children, the testing of interventions for black women with AIDS, and prevention studies (National Center for Nursing Research, personal communication, 1992). Nevertheless, as the HIV pandemic continues to grow and expand its demographic parameters, more research, particularly with such populations as women and children, is urgently needed. Studies exploring prevention issues and symptom management also are most important. Some suggestions for future study include examination of cultural variables associated with coping with HIV and AIDS; longitudinal research on surviving HIV over time; intervention studies to test specific nursing therapeutics in various settings such as hospital, home, and clinic; and finally, research describing the impact of HIV and AIDS on family functioning and adaptation. It is only through continued study of the impact of HIV, on both the individual living with HIV, and his or her significant others, that we will expand nursing knowledge and strengthen nursing care for those impacted with this fearsome and life-threatening condition. PMID- 8516176 TI - Delivery systems for the care of persons with HIV infection and AIDS. AB - HIV infection and AIDS are pathologic conditions that more than any other disease require the concerted, cooperative efforts of the health care profession and the community. This article discusses the development of delivery systems for the care of persons with HIV infection and AIDS, highlights what systems have been successful, and indicates the areas in which further research and development are needed. Topics discussed include the costs of care; identifying and meeting the specific health care needs of the HIV-infected population; and long-term, community-based, hospice, and hospital care. PMID- 8516177 TI - Cognitive impairment in the elderly. AB - This article reviews research related to assessment and interventions for cognitive impairment conducted by nurses as principal and coinvestigators. It focuses on the broad areas of delirium and dementia, which are divided into assessment and intervention-related research. The intervention research begins with descriptive studies and has subdivisions for primary and secondary symptoms. Ideas for future research follow. PMID- 8516178 TI - Family caregivers of institutionalized and noninstitutionalized elderly individuals. AB - This article provides an overview of the literature that has examined the issues of institutionalization and community care of elderly persons. Specifically, those studies are discussed that report on the family's decision to institutionalize the elderly person and those that report on the effect of institutionalization of the family. Studies about community caregiving that report on caregiver characteristics, the stress of caregiving, and interventions to manage care issues and caregiver stress also are detailed. Implications for nursing research and practice can be derived from the article. PMID- 8516179 TI - Physical impairments in the elderly population. AB - The model presented here provides a starting point for considering the physical impediments that accompany biologic aging. The scientific challenge for the future is to identify how specific modifiable variables can attenuate these physical impediments and distinguish them from those changes that are truly irreversible accompaniments of aging. The humanitarian challenge facing all health care professionals is to provide compassionate care, emotional support, and unfailing commitment to aging persons as they experience changes in physical function and role performance. PMID- 8516180 TI - Dyspnea and fatigue. AB - Research regarding dyspnea and fatigue has focused on the factors contributing to the symptoms. Physiologic factors, such as muscle use; psychological factors, such as anxiety and depression; and situational factors, such as hot weather, contribute to the symptoms of dyspnea and fatigue. Increased symptoms lead to impaired functional ability. Strategies for relief of dyspnea and fatigue can be obtained from patient report, but further research is needed to test the effectiveness of nursing interventions. PMID- 8516181 TI - Sleeplessness. AB - This article identifies and reviews research related to sleeplessness reported by nurses in the literature. The current state of clinical nursing research as it relates to sleep is evaluated, including the content, methodology, and implications for further research. Although the review indicates current interest in sleep by clinical nurse researchers, the number of nursing studies in the literature is limited, especially within specific areas, such as age groups and setting. Also, directions for future nursing research on sleep are recommended. PMID- 8516182 TI - Clinical nursing informatics. Developing tools for knowledge workers. AB - Current research in clinical nursing informatics is proceeding along three important dimensions: (1) identifying and defining nursing's language and structuring its data; (2) understanding clinical judgment and how computer-based systems can facilitate and not replace it; and (3) discovering how well-designed systems can transform nursing practice. A number of efforts are underway to find and use language that accurately represents nursing and that can be incorporated into computer-based information systems. These efforts add to understanding nursing problems, interventions, and outcomes, and provide the elements for databases from which nursing's costs and effectiveness can be studied. Research on clinical judgment focuses on how nurses (perhaps with different levels of expertise) assess patient needs, set goals, and plan and deliver care, as well as how computer-based systems can be developed to aid these cognitive processes. Finally, investigators are studying not only how computers can help nurses with the mechanics and logistics of processing information but also and more importantly how access to informatics tools changes nursing care. PMID- 8516183 TI - Strategies for maintenance of health-promoting behaviors. AB - With our understanding of health expanding to include a dynamic of well-being, definitions of health vary, and activities associated with health promotion and disease prevention often overlap. Consequently, studies of health-promotion research include risk reduction. Most nursing studies are descriptive and cross sectional, and although other disciplines report more intervention efforts, the same theoretic, definitional, and measurement issues exist in all studies. Women, older adults, and those better educated report a greater number of health promoting behaviors and engage in a healthier lifestyle. An individual's view of health may affect his or her motivation to perform health-promoting behaviors. Removal of barriers, creation of supportive environments, and a strong sense of self-efficacy are important aspects of adoption and maintenance of health promoting behaviors. Development of self-efficacy should be an integral part of health-promotion programs as increases in self-efficacy have been shown to precede the adoption and maintenance of health-promoting behaviors. Goal setting, contracting, and other behavioral techniques can help an individual develop competence in self-regulation of behavior. Outcomes of research must be congruent with the long-range view that promotion of health implies. Short-term outcomes may continue to be specific, but longer-term indicators will be more comprehensive. Measurement difficulties include evaluation of large-scale programs over extended periods, accounting for positive change in samples in which some persons already maintain health-promoting behaviors and proxy measures for future health. Future attention must be directed toward promoting healthy lifestyles and development of "wellness" thinking. PMID- 8516184 TI - The impact of technology on patients and families. AB - The continuing evolution of the highly specialized, technologic manner in which we provide care in critical care units has potentially hazardous effects on the physical and psychological well-being of patients and family members. Although the ICU environment possesses characteristics that make patients and families prone to undesirable sequelae, critical care nurses can employ creative strategies to minimize the impact of bedside technology that is so important for the survival and recovery of the critically ill patient. Strategies to reduce the psychological impact of the ICU environment begin with a psychosocial assessment of the meaning patients and families attach to bedside technology. This assessment will strengthen nurse, patient, and family interactions, as well as guide patient and family education and sensory information to reduce fear and anxiety often associated with threatening procedures. Facilitating touch and family involvement in the patient's care during visitation is another strategy to humanize the technologic environment. Managing the environment is essential to reduce the physical impact of the ICU environment. Nurses can manipulate the use of equipment to reduce crowding and noise at the bedside, foster familiar activities to stimulate the patient's other senses, and facilitate sleep patterns by structuring nursing activities and providing comfort measures. These nursing interventions will reduce the effects of sensory overload/deprivation and sleep deprivation and, it is hoped, prevent ICU psychosis. PMID- 8516185 TI - Technology dependency and iatrogenic injuries. AB - Research on iatrogenic injuries and technology dependency is sparse in light of the expansive use of technology in health care today. Many of the publications are single case reports of an iatrogenic injury related to a specific type of device. Little has been done to analyze these reports in a collective fashion. Nursing research is especially limited, and most studies were located in the medical literature. The majority of research has been done in pediatric populations with major emphasis on respiratory and nutritional technology. In contrast, little research has been done with adults who are ventilator dependent. Perhaps the paucity of research in this area is related to the Food and Drug Administration (FDA) requirements for technology safety before placement of a device on the health care market with the subsequent assumption by health care personnel that the technology is safe and effective. The challenge for the future is to build programs of nursing research that (1) describe the incidence and nature of iatrogenic injuries associated with technologies that are of high volume and for which many patients are dependent and (2) to tests ways to prevent iatrogenic injuries associated with technologies often used in nursing practice. PMID- 8516186 TI - Critical issues for the development of clinical nursing knowledge. AB - This article reviews the other articles in this issue that provide evidence of recent progress in clinical nursing research. The authors, guest editors of this issue, issue a call for further research to develop improvements in clinical nursing practice. PMID- 8516187 TI - The Chernobyl accident, congenital anomalies and other reproductive outcomes. AB - Studies of the association between the Chernobyl accident in April 1986 and reproductive outcome, with particular reference to congenital anomalies, are reviewed. All of the studies so far have been based on the detection of a change in frequency over time. An increased frequency of trisomy 21 in the former West Berlin in January 1987, and increases in the frequency of neural tube defects in several small hospital-based series in Turkey, are not confirmed in larger and more representative series in Europe. No clear changes in the prevalence at birth of anomalies which might be associated with the accident are apparent in Byelorussia or the Ukraine, the republics with the highest exposure to fallout. However, these data are difficult to interpret as the methods of acquisition have not been described and they have not yet been reported in full. Thus, there is no consistent evidence of a detrimental physical effect of the Chernobyl accident on congenital anomalies. This is also the case for other measured outcomes of pregnancy. There is evidence of indirect effects--an increase in induced abortions substantial enough to show as a reduction in total births, due to anxieties created. Data are not available on the reproductive outcomes of women pregnant at the time of the accident who were evacuated from the 30 km zone of immediate contamination, of workers in the plant at the time of the accident or of decontamination workers. Moreover, no data are available from several of the other countries closest to the Chernobyl area. PMID- 8516188 TI - Fumes from the spleen. PMID- 8516189 TI - Cystic fibrosis in the United Kingdom, 1968-1988: incidence, population and survival. AB - A thorough survey was conducted of patients with cystic fibrosis living in the UK from 1977 onwards. This was supplemented with death certificate data back to 1968. There was one case identified for each 2475 births. The total number of cases in the UK rose linearly from 4086 in 1977 to 5426 in 1988 and is estimated to be 6000 in 1992. The probability of survival improved in the period under study for all age groups and in both sexes. It was worst in the first year of life, dropped sharply thereafter but then increased steadily with age. There has been a very marked improvement over the years in survival in the first year of life, but a lesser one in older age groups. Male mortality was greater than that in females in the first year of life, but less in subsequent years giving, overall, worse survival for females. A set of cohort and 'current' survival graphs for the two sexes are given. PMID- 8516190 TI - A case-control study to investigate the role of recent spontaneous abortion in the aetiology of neural tube defects. AB - Clarke et al. suggested that women who have had a spontaneous abortion are at an increased risk in their next pregnancy of producing an offspring with a neural tube defect (NTD). A matched case-control study was carried out to test the related hypothesis that a spontaneous abortion occurring in the 6-month period prior to the conception of a pregnancy (recent spontaneous abortion) is a risk factor for the development of an NTD in that pregnancy. The cases were 177 singleton pregnancies to non-primigravida Leicestershire women, which were affected by non-syndromal NTDs between 1976 and 1989. Two control pregnancies were matched with each case on intended place of delivery and date of maternal last normal menstrual period (LNMP). After adjusting for potential confounders, recent spontaneous abortion was found to be associated with a decreased relative risk of neural tube defect, odds ratio 0.46, 95% confidence interval 0.20, 1.07. The result provided little evidence in favour of the hypothesis, suggesting instead that prior spontaneous abortion has a protective effect in relation to subsequent NTD development rather than being a major risk factor in the aetiology of NTDs. PMID- 8516191 TI - Small-for-gestational-age term birth: the contribution of socio-economic, behavioural and biological factors to recurrence. AB - This paper follows a previous study comparing women who had repeatedly given birth to small-for-gestational-age (SGA) term infants ('repeater' mothers) with multiparous women who had had only one such infant ('non-repeater' mothers). The present investigation involves the individual matching of each woman in the above groups with a control mother whose offspring were all term non-SGA infants. The study was based on all Western Australian Caucasian women giving birth to singletons and the study population comprised 594 repeater cases with 594 matched controls and 935 non-repeater cases with 935 matched controls. Conditional logistic regression analyses indicated that demographic and paternal factors were significant predictors for recurrent SGA term birth whereas obstetric conditions, particularly preeclampsia, were important for the prediction of isolated SGA term birth. Maternal smoking, low maternal birthweight and lack of higher educational qualifications were associated with both types of SGA birth. After multivariable analyses, a strong and significant association remained between having a first infant as a teenager and recurrent SGA term birth. The tendency to repeat SGA term birth appears to be associated with social, economic and behavioural disadvantage and is unlikely to be ameliorated without fundamental changes in society. PMID- 8516192 TI - Low birthweight and risk of mild mental retardation by ages 5 and 9 to 11. AB - This prospective analysis assessed the risk of mild mental retardation (MMR) associated with low birthweight (LBW) in the Child Health and Development Studies. Scores of 50-70 on the Raven Progressive Matrices, a relatively culture free test of cognitive functioning, were used to categorize MMR. At the age of 5, 13.8% of the 195 children with birthweights less than 2500 g (LBW) were MMR, whilst 4.2% of the 2293 children with normal birthweights (> 2955 grams) were MMR. After adjusting for confounders (maternal age, race, education, prenatal alcohol use, maternal conditions, and congenital anomalies), the relative risk of MMR for LBW was 3.4 (95% CI 1.2-5.4). For children aged 9-11, 7.7% of 194 LBW children were MMR, compared with 6.2% of the 2546 with normal birthweights; the adjusted relative risk for LBW was 1.2 (95% CI 0.7-2.0). Although a strong association between LBW and MMR was observed for both blacks and non-blacks at the age of 5, the association between birthweight and MMR was apparent only for blacks in the cohort of children aged 9-11. These findings suggest that race, a marker for environmental factors which were not measured in this study, may modify the LBW and MMR relationship. PMID- 8516193 TI - Risk factors associated with low Apgar scores in a low-income population. AB - The purpose of this study was to identify risk factors associated with Apgar scores of less than 7 in newborns scored at 5 minutes after birth. All newborns were delivered at Grady Memorial Hospital, Atlanta, Georgia, which primarily serves a low-income population. The data were obtained from the obstetric discharge records for 1985-89. In this case-control study, 939 newborns with Apgar scores of less than 7 were compared with 2817 newborns with Apgar scores of 7 or higher. Low birthweight (< 2500 g) and short gestational age (< 37 weeks) were each significantly associated with low Apgar scores. Race was not a significant risk factor for low Apgar scores in this low socio-economic population. It is also demonstrated that maternal risk factors (pregnancy-induced hypertension, prolonged rupture of membranes), method of delivery (caesarean, repeat caesarean, vaginal birth after caesarean section) and male sex were significantly associated with Apgar scores of less than 7. As a result of the risks that were found to be associated with method of delivery, further study of the risks associated with caesarean delivery and of the relative advantage of a caesarean delivery versus vaginal delivery after a previous caesarean section is advocated. PMID- 8516194 TI - Congenital malformations in babies born after assisted conception. PMID- 8516195 TI - DES and preterm birth rate. PMID- 8516196 TI - [Arterial hypertension in patients with diabetes type II with regard to treatment principles]. PMID- 8516197 TI - [Nutritional recommendations for patients with diabetes mellitus type II]. PMID- 8516198 TI - [Verification of indications for using oral treatment in patients with diabetes type II and obesity. Test treatment with diet in light of personal experience]. PMID- 8516199 TI - [Clinical pharmacotherapy in non-insulin-dependent diabetes (type II)]. PMID- 8516200 TI - [Late complications of diabetes mellitus type II (non-insulin- dependent)]. PMID- 8516201 TI - [Changing from using oral treatment to insulin in non-insulin- dependent diabetes]. PMID- 8516202 TI - [Epidemiologic trends in type II diabetes]. PMID- 8516203 TI - [Clinical evaluation of gliquidone--short acting sulfonylurea derivative- comparison with glibenclamide and gliclazide]. PMID- 8516204 TI - [Use of angiotensin I converting enzyme inhibitors --essential progress in treatment of hypertension and late complications in patients with non-insulin dependent diabetes mellitus]. PMID- 8516205 TI - [Method of treatment and platelet aggregation in patients with diabetes mellitus type II]. AB - Platelet aggregation after ADP administration in 84 diabetic patients and in 14 healthy subjects were examined. ADP concentration indispensable to start aggregation, velocity and intensivity of this process using Born method were measured. In diabetic patients (independently of kind of therapy) the increase platelet aggregation activity were found (significant difference between kind of insulin therapy). PMID- 8516206 TI - [Effect of short term hypoglycemic treatment with gliclazide and gliquidone on platelet function in patients with diabetes mellitus type II]. PMID- 8516207 TI - [Gliquidone--opinions from the international literature]. PMID- 8516208 TI - [Idiopathic and apparent associations between obesity and non-insulin-dependent diabetes and certain other disturbances: therapeutic findings]. PMID- 8516209 TI - [Pathogenic mechanisms in non-insulin-dependent diabetes mellitus]. PMID- 8516210 TI - Spindle cell (leiomyomatous) rhabdomyosarcoma, a rare variant of embryonal rhabdomyosarcoma. AB - A rare case of the leiomyomatous variant of embryonal rhabdomyosarcoma is reported. A 13-year-old boy presented with a recurrent painless mass on the ventral side of the right forefoot. Microscopically, the tumor consisted of spindle-shaped and round tumor cells in a fascicular or storiform, focally hemangiopericytoma-like growth pattern. The cytoplasm of the spindle-shaped tumor cells was eosinophilic and fibrillary, in some areas resembling smooth muscle cells. Immunohistologically, all tumor cells were vimentin-positive, most of them also stained with antibodies to desmin and muscle specific actin (MSA). In addition, many tumor cells showed a co-expression of alpha-sarcomeric actin and myoglobin. All tumor cells were negative with alpha-smooth muscle actin. Two years after surgical treatment and chemotherapy the patient is well with no evidence of distant metastases. The clinicopathological features and differential diagnostic problems are discussed. PMID- 8516211 TI - What is new in our understanding of multifocal breast cancer. AB - Because of the increasing frequency of breast conserving surgery, the significance of multifocal breast carcinoma has been reexamined. Multifocal breast carcinoma can be detected in at least 30% of radical mastectomy specimens, even if the index tumor is small and non-palpable. The actual percentage depends on the method of examination of the breast. Simulated tylectomy performed on mastectomy specimens has revealed potential foci of residual tumor in up to 80% of cases. However, the majority of these are close to the index tumor and are generally included within the usual margin of normal tissue removed along with the carcinoma. The difference in the recurrence rate following tylectomy with and without post-operative irradiation (approximately 25% vs 5%) indicates that these foci are clinically important. Most of the "recurrences" occur in the vicinity of the index tumor and within 4 years of the initial treatment. Beyond 5 years, "recurrences" tend to occur at sites remote from the index tumor and at a steady but much lower rate over the next decade; a rate that approximates to that of new primaries in the contralateral breast (1% per year). These late "recurrences" carry a relatively good prognosis. This biphasic pattern of recurrence emphasizes that multifocal breast cancer is a significant factor in both the short- and long term management of patients treated by breast conserving surgery. PMID- 8516212 TI - Cytokine (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6)-possessing cells in lymph nodes of malignant lymphoma. AB - Interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, and IL-6 are the most important triggers in the response of the immune system to infection and neoplasia. We examined the histochemical distribution of cytokine-possessing cells in neoplastic lymph nodes of 68 malignant lymphomas. The HLA-DR positive interdigitating reticulum cells (IRCs), histiocytes/macrophages (H/Ms) and epithelioid histiocytes with these cytokines were frequently encountered in Hodgkin's disease, B cell lymphoma of lymphoplasmacytic/cytoid, centroblastic and immunoblastic types, and T cell lymphoma of Lennert's and anaplastic large cell types. In almost all cases of B cell lymphoma of chronic lymphocytic leukemia, centrocytic, follicular centroblastic/centrocytic, Burkitt's types and T cell lymphoma of lymphoblastic, angioimmunoblastic lymphadenopathy and pleomorphic types, the cytokine-possessing cells were rarely or occasionally present. These lymphomas with less cytokines had also few or occasionally encountered IRCs, while H/Ms were frequently or occasionally present. Well-developed dendritic reticulum cells in some types of lymphoma had few cytokines. The population of cytokine-possessing cells was related with histologic type of lymphoma and the volume of IRCs. The IRCs might act as an important initiator of reactive cells against tumor cells. In addition, neoplastic T cells influenced the cytokines' possession of IRCs and H/Ms. Although lacunar, Hodgkin's and Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells in peripheral T cell lymphoma showed weak positive reaction of TNF alpha in one third of the cases, lymphoma cells in the majority might have few cytokines, especially IL-1s and IL-6. PMID- 8516213 TI - Placental thrombi and other vascular lesions. Classification, morphology, and clinical correlations. AB - Vascular lesions, most often mediated by thrombi, are second only to infections as a cause of fetal injury in the later weeks of pregnancy. In our experience many pathologists who examine placentas fail to conduct a proper search for vascular lesions and some even fail to recognize those exposed by their examination. This review is intended to define the typical clinical background or circumstances that suggest the presence of significant vascular problems, to define techniques calculated to display them well, and to identify criteria for diagnosis. Further research is needed to evaluate the prevalence of maternal and fetal hypercoagulable states and thrombi as a cause of fetal injury. PMID- 8516214 TI - The immunophenotype of Ewing's sarcoma. An immunohistochemical analysis. AB - Since 1963, 53 cases of Ewing's sarcoma have been diagnosed at the N. Goormaghtigh Institute of Pathological Anatomy. All tumours were classified according to their growth pattern as described by Kissane: diffuse, lobular or organoid, the latter with pseudorosettes, or belonging to the fillagree type. In 45 cases, an immunohistochemical examination was carried out on routinely processed material in order to determine the immunophenotype of the tumours and to get more information on the histogenesis of the tumours. Antibodies against cytokeratin, desmin, vimentin, neurofilaments, neuron-specific enolase, Leu7, synaptophysin, chromogranin, the muscle-specific actin, the Von Willebrand factor and the common leucocyte antigen were used in a biotin-streptavidin procedure. The presence of neural markers such as neuron-specific enolase, synaptophysin and Leu7 was proved in the majority of the cases. The expression of the three markers was absent in only two cases. Neurofilaments were demonstrated to be present in 5 of the 6 cases for which fresh material was available. The results of this study point towards a possible neuroectodermal origin of Ewing's sarcoma. This is in agreement with the results of cell culture experiments and of cytogenetic studies. PMID- 8516215 TI - Osteoblastoma and osteoid osteoma. Clinical and morphological features of 162 cases. AB - A study of 46 osteoblastomas and 91 osteoid osteomas, selected from a total of 162 cases proceeding from 15 Spanish Hospitals was done to establish epidemiological data on clinico-pathological parameters and to compare them with the findings of other authors. A comparative study between both tumors is done and emphasis is put on the discussion of aggressive osteoblastoma. PMID- 8516216 TI - Informational analysis of morphometric parameters of pulmonary heart in chronic nonspecific pulmonary diseases. AB - The difference between macro- and micrometric parameters of the right ventricle of the heart was studied in 26 autopsy cases of chronic nonspecific pulmonary disease, and 11 cases of violent death without pulmonary or cardiac disease from the institute of forensic medicine, matching in age and sex with the first group. The results obtained from organ and tissue analysis enabled us to determine the most informative parameters common for compensation and decompensation status of cor pulmonale: Width, wall thickness, and weight of the right ventricle, thickness of cardiomyocytes and cross-section of their nuclei. Analysis of morphometric parameters at the compensation stage revealed a specific diagnostic value in the circumference of the pulmonary artery and the volume density of focal cardiomyocytic lesions. For the decompensation stage, it was possible to gain specific diagnostic information from the length of inflow into the right ventricle, and from the volume and density of sclerotic foci. PMID- 8516217 TI - Morphometric study of the bone marrow in polycythemia vera following interferon alpha therapy. AB - Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphometrical parameters of megakaryocytes was also remarked. Reticulin fibrosis was mild in 13 cases and moderate in 6 cases before IFN therapy. Reticulin content was unmodified during therapy in all cases but two, in which fibrosis changed from mild to moderate. In conclusion IFN therapy is to be considered a good method in polycythemia vera for the control of proliferative activity of bone marrow but with IFN therapy one cannot determine regression of marrow fibrosis. PMID- 8516218 TI - AIDS-myelopathy. A neuropathological study. AB - Vacuolar myelopathy belongs to the AIDS-associated diseases. It is characterized by vacuolation and infiltration of the long tracts of the spinal cord by macrophages. The clinical and morphological findings of 8 AIDS-patients with vacuolar myelopathy are reported here. The syndrome developed during the final stages of AIDS and was associated with HIV-encephalopathy in 5 cases. The vacuoles were mainly due to intramyelinic swelling and vacuolation. Vacuolated macrophages and axons contributed only to a minor degree. In one case only, HIV antigens were detected immunohistochemically. The results are discussed in the light of modern pathogenetical concepts of HIV-related diseases. PMID- 8516219 TI - Differentiation of brown adipose cells in three-dimensional collagen gel culture. AB - Brown adipose cells are heat-producing cells through non-shivering thermogenesis by intramitochondrial "thermogenin". This specific protein is a marker for their cellular differentiation. It has long been known that cultured brown adipose cells in monolayer rapidly lose the thermogenin bioactivity. In this study, we cultured brown adipose cells in three-dimensional type I collagen gel matrix. Under this culture condition, they were able to survive, and differentiated morphologically and functionally for a long period of time, especially exhibited the characteristic immunohistochemical activity of thermogenin. These findings suggest that brown adipose cells differentiate in type I collagen gel. In this condition, cholera toxin or BRL 37344, one of beta 3-adrenoceptor agonists, specifically stimulated the brown adipose cells. PMID- 8516220 TI - Atypical lung carcinoid with GFAP immunoreactive cells. AB - A case of atypical carcinoid with peculiar histological and ultrastructural pattern and immunohistochemical phenotype is presented. The neoplasm is composed of three types of cells. Type 1 cells are small to medium sized, fusiform, with scarce cytoplasm and are arranged in fascicles. Type 2 cells are cuboidal and line acinar structures. Type 3 cells have more abundant eosinophilic cytoplasm, larger nuclei and are arranged in fascicles intersecting with fascicles of type 1 cells, and sometimes surround acinar structures. The three cell types are present both in the primary lesion and in its lymph node metastases. Immunohistochemistry demonstrates immunoreactivity of all cell types for general neuroendocrine markers. Cytokeratin immunoreactivity is more prominent in type 1 and 2 cells, and is only focally expressed in type 3 cells. Type 3 cells are also immunoreactive for glial fibrillary acidic protein (GFAP), alpha-actin, S-100 protein, vimentin. Electron microscopic examination confirms the neuroendocrine nature of the cells, and show that type 3 cells have prominent bundles of intermediate filaments, electron-dense granules and junctional complexes. To our knowledge, this is the first case of atypical lung carcinoid with GFAP immunoreactivity. The nature of type 3 GFAP positive cells is unclear. There are some clues pointing to their sustentacular nature, and other ones pointing to a myoepithelial origin, but the data are inconclusive. Type 3 cells may be the malignant counterpart of sustentacular cells seen in typical carcinoids, but their GFAP positivity and the presence of electron-dense granules are very unique features, which differentiates them from sustentacular cells. Alternatively, their unusual GFAP + immunohistochemical phenotype may be due to aberrant expression of cytoskeletal proteins. PMID- 8516221 TI - Primary T-cell malignant lymphoma of the central nervous system. Histological, immunohistochemical and ultrastructural study of a case. AB - Most primary malignant lymphomas (ML) of the central nervous system (CNS) are derived from B-cells, whereas T-malignant lymphomas (T-ML) primarily arising in the CNS are extremely rare. We report on a patient with a primary T-ML of the CNS localised in the posterior fossa. On the basis of histological, ultrastructural and immunohistochemical studies, this tumour was classified as a pleomorphic T ML, medium and large cell type with peripheral helper/inducer T-cell phenotype (CD 1-, CD 2+, CD 3+, CD 5+, CD 7-, CD 4+, CD 8-, CD 19-, CD 22-, UCHL 1+/CD 45 RO, L 26-/CD 20, LN 1-/CDW75, LN 2-/CD 74, MB 2-). Furthermore, the positivity of the markers CD 25 and HLA-DR on many medium-sized and large lymphoma cells suggests activation of these cells. The nuclear marker of proliferative activity Ki-67 was expressed in some large cells, whereas the natural killer cell-related markers CD 16 and Leu 7/CD 57 did not react with lymphoma cells. This study emphasises the value of extensive immunohistochemical investigations on frozen and paraffin sections in order to identify and characterize the T-cell malignancies, particularly in their rare CNS location. PMID- 8516222 TI - Cardiac involvement in a child with unsuspected pseudoxanthoma elasticum. PMID- 8516223 TI - Multicentric bilateral renal cell carcinomas and a vascular leiomyoma in a child. AB - We report a unique case of multicentric bilateral renal cell carcinomas and a simultaneous large renal vascular leiomyoma in an 11-year-old child with sickle cell anemia. The patient presented with several episodes of massive hematuria. Abdominal sonography and computed tomography demonstrated bilateral renal neoplasms and the patient was clinically thought to have bilateral Wilms' tumor. An initial biopsy of the lower pole of right kidney revealed a renal cell carcinoma. Accordingly, bilateral renal angiography followed by right total nephrectomy and left upper pole partial nephrectomy were performed. Pathologic studies showed multicentric, bilateral renal cell carcinomas (two in the right kidney and one in the left kidney), of clear, granular, and oncocytic cell types. A simultaneous large vascular leiomyoma was also present in the right kidney. The smooth muscle nature of the leiomyoma was determined by light microscopy, immunohistology, and electron microscopy. The diagnostic difficulties in distinguishing them from other renal tumors are discussed. PMID- 8516225 TI - Galactocele in a male infant: case report and review of literature. AB - An 11-month-old male developed painless enlargement of the left breast over 1 month. The lesion was mobile, fluctuant, and nontender. Surgical excision was performed and histological examination revealed a galactocele. A galactocele is a very rare cause of breast enlargement in male infants and children. PMID- 8516224 TI - Neonatal tuberculosis. AB - We present an autopsy case of neonatal miliary tuberculosis in a 36-day-old baby that was born to a mother who had no symptoms. Histopathological examination of lungs revealed necrosis and numerous acid-fast bacilli. Mycobacterium tuberculosis hominis was isolated by guinea pig inoculation with lung tissue. Three months after dietary the mother was admitted with pleural effusion and endometrial biopsy showed a granulomatous inflammation compatible with tuberculosis. Intrauterine infection was considered and that was supported by retrospective findings of the endometrial biopsy. We also want to emphasize the importance of searching for genital tuberculosis even if the mother has no symptoms. PMID- 8516226 TI - Congenital cystic adenomatoid malformation within an extralobar pulmonary sequestration. AB - A type II congenital cystic adenomatoid malformation (CCAM II) occurring within an extralobar pulmonary sequestration (ELS) is described. This large malformation and accompanying pulmonary hypoplasia were diagnosed prenatally by ultrasound examination at 24-25 weeks gestational age. Based upon this diagnosis, the pregnancy was terminated. Autopsy revealed a 40.5 g supradiaphragmatic sequestration, severely hypoplastic lungs, and a hypoplastic heart. Morphologic and clinical features of both CCAM and ELS are compared. CCAM occurring within an ELS has been reported on at least twelve occasions. All the malformations in which the type was reported were of the less differentiated types II or III. We offer an explanation of this fact based on the timing of the embryologic maldevelopment. PMID- 8516227 TI - Astroblastoma: report of a case with ultrastructural, cell kinetic, and cytogenetic analysis. AB - Astroblastomas are rare tumors of cerebral hemispheres of young adults. We report an astroblastoma in a 15-year-old girl and present the first descriptions of cytogenetic abnormalities in this tumor. The tumor was relatively well demarcated from the brain and revealed prominent perivascular rosettes as well as intervascular clear cells that contained abundant glycogen. Cytogenetic analysis revealed an abnormal hypodiploid karyotype with 45 chromosomes and monosomies of chromosomes 10, 21, and 22 and two marker chromosomes in all cells examined. The tumor had a Ki-67 labelling index of 4.7% and assessment of ploidy by flow cytometry revealed 96% of cells in the G0G1 phase and 4% of cells in the G2M phase. Assessment of proliferation and ploidy indices in further cases may provide important prognostic data for this poorly understood entity. Further cytogenetic studies will also help to identify if there are consistent karyotypic abnormalities in these enigmatic tumors. PMID- 8516228 TI - Renal developmental arrest in sudden infant death syndrome. AB - Investigations linking sudden infant death syndrome (SIDS) and type II intrauterine growth retardation (IUGR) have thus far failed due in part to technical limitations. Recently developed stereological methods for the unbiased estimation of total nephron number in the human kidney are capable of detecting deviations from normal values of greater than 10%. We compared the total number of nephrons in the kidneys of 24 SIDS victims with those from 16 controls with the same age range. Mean nephron number was significantly (P < 0.001) reduced in ex-IUGR SIDS cases (birthweight under the 10th centile, n = 9, mean number 635,000, range 327,000-1,010,000) in comparison with controls (903,000, 740,000 1,060,000). A similarly significant (P < 0.01) reduction in the "normal birthweight" SIDS group (birthweight over 10th centile, n = 15, 690,000, 361,000 1,040,000) was found. This hitherto unreported renal developmental arrest may be only one manifestation of a general, somatic developmental defect, reflecting adverse intrauterine conditions; other organ systems, similarly critical to homeostasis may be comparably affected. The findings, although not proposed as direct cause of SIDS, may represent a potential explanation for the recognized association of IUGR and SIDS, and provide--we believe--the first quantitative evidence of intrauterine growth retardation in, at least a number of, children of average birthweight. PMID- 8516229 TI - Necrotizing enterocolitis: a review of pathogenetic mechanisms and implications for prevention. AB - Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature neonates that accounts for 3000 to 4000 deaths each year in the United States. The pathogenesis is not well understood, however theories suggest that prematurity, enteral feeding, bacterial colonization, and intestinal ischemia contribute to the intestinal injury. Furthermore, recent studies have shown that platelet activating factor and perhaps other inflammatory mediators mediate bowel necrosis in animals and possibly in humans. Although no specific intervention for NEC treatment exists, preventive therapy using either enteral IgA supplementation, breast milk feeding, antibiotic prophylaxis, or exogenous steroid administration have reduced the incidence of this overwhelming disease in small randomized trials. These modalities and perhaps PAF antagonists or other inflammatory mediator inhibitors may reduce the incidence or severity of NEC in the next several years. PMID- 8516230 TI - Fluid and electrolytes: clinical aspects. PMID- 8516231 TI - Index of suspicion. Case 1. Infant botulism. PMID- 8516232 TI - Index of suspicion. Case 2. Ankylosing spondylitis. PMID- 8516233 TI - Index of suspicion. Case 3. Spinal cord lesion. PMID- 8516234 TI - Sudden infant death syndrome. PMID- 8516235 TI - Tropical pediatrics. AB - Tropical pediatrics often is more a study of the consequences of poverty than of exotic infections. Pediatricians involved with the care of children in or from the tropics must deal with poverty, place an appropriate emphasis on preventive medicine, and seek to bridge their own cultural and linguistic barriers. Malaria, diarrheal disease, and malnutrition account for a large part of pediatric morbidity and mortality in tropical countries. P falciparum can cause severe malarial disease. Treatment must be initiated promptly; resistance to antimalarial drugs is possible. Hygienic and nutritional prevention of diarrhea must be coupled with widespread use of oral rehydration therapy for acute cases of diarrhea. Identification and early treatment of mildly malnourished children can prevent some of the mortality of overt marasmus and kwashiorkor. PMID- 8516236 TI - Feeding the very low-birth-weight infant. PMID- 8516237 TI - Bronchiolitis. PMID- 8516238 TI - Releasing penile foreskin trapped in a zipper. PMID- 8516239 TI - Vulvovaginitis in the child and adolescent. PMID- 8516240 TI - Near-drowning. PMID- 8516241 TI - Index of suspicion. Case 1. Sliding hiatal hernia. PMID- 8516242 TI - Index of suspicion. Case 2. Acute cholecystitis. PMID- 8516243 TI - Index of suspicion. Case 3. Aseptic meningitis with aphasia. PMID- 8516244 TI - [From phosphorylase kinase...to a thousand and one protein kinases?]. PMID- 8516245 TI - [Glutathione metabolism]. PMID- 8516246 TI - [Analogs of vitamin D and antiproliferative activity]. PMID- 8516247 TI - [Analogs of vitamin D for photoaffinity labeling of transporting proteins and vitamin hormone receptors]. PMID- 8516248 TI - [Erythroid and nonerythroid spectrins--structure and function]. PMID- 8516249 TI - [Phytochelatins--heavy metal-binding peptides of plants]. PMID- 8516250 TI - 82nd Annual Meeting of the Poultry Science Association, Inc. and 14th Annual Meeting of the Southern Poultry Science Society. 1993. Abstracts. PMID- 8516251 TI - Continuity, change, challenge. PMID- 8516252 TI - Vision for the future of public health nursing: a case for primary health care. AB - Canada has embraced the goal of the World Health Organization to achieve health for all. This has created a paradigm shift from a focus on direct care to include health promotion and community development, consistent with a primary health care approach. Nevertheless, a clearly articulated vision for the role of public health nurses (PHNs) is lacking. Despite the fact that PHNs make up the largest group of health care workers in the community, their collective opinions and ideas regarding their own practice are seldom sought in a systematic manner. We conducted a survey of public health nurses in British Columbia. Using a two-wave Delphi approach, PHNs were asked to define issues for the future of public health nursing, and to state publicly their preferences for change and transformation. The responses were rank ordered, analyzed, and compared with recent nursing and health care literature to interpret their content. The PHNs' visions for tomorrow agree with concepts of primary health care and community development, and have implications for community health nursing's practice and education. PMID- 8516254 TI - Application of a model for public health nursing program planning. AB - Community health nurse (CHN) specialists have advanced educational preparation in both nursing and the public health sciences. They are called on to perform numerous advanced practice roles in public health and other community agencies, one of which is program planning. To perform this role effectively, CHN specialists should use conceptual models to guide application of the nursing process in a population-based practice. One such model developed by a nurse for use in planning community health programs is the McLaughlin model. It was used to address the community diagnosis of risk for childhood lead poisoning, a long standing public health problem currently receiving renewed attention from federal public health authorities. Applications of conceptual models in practice settings can test such model's efficacy, enrich the scientific basis of community health nursing practice, and ultimately improve the health of the community. PMID- 8516253 TI - Social networks and social support of recently divorced women. AB - A study of the support networks and social support of recently divorced women with children was conducted over two years. Its purpose was to assess changes in the women's social support and identify their unmet needs. Data were collected from 148 women by mailed questionnaire and telephone interview soon after the final divorce decree, and again at two years. The women did experience a significant decrease in network size and social support over two years; however, the primary members of their networks--family and friends--remained stable. Women with preschool-age children had more family support than those with older children. Nine categories of unmet needs were identified. Most frequently cited, in descending order, were emotional support, financial assistance, need for a boyfriend/partner/spouse, time for herself, and child care. The average number of needs per woman was less than two. The findings of this study confirm the losses in overall network size and support that women experience after divorce. The identification of unmet needs helps nurses to target areas in which women may require assistance to find social support. PMID- 8516255 TI - One hundred years of powerful women: a conversation with Dorothy Talbot. Interview by Marion E. Highriter. PMID- 8516256 TI - Definitions of health and health goals of participants in a community-based pulmonary rehabilitation program. AB - Improving health is the goal of community-based rehabilitation programs. However, different conceptions of health between health care providers and participants inhibits communication, leads each group toward different goals, and causes dissatisfaction among participants who feel their individual goals are not being met. This study compared definitions of health, and the health goals of participants in a nurse-managed community respiratory rehabilitation program with those of the program. The majority of 132 adults with chronic respiratory disease defined health in terms of absence of disease and its symptoms, or as the ability to function within the community. Their goals paralleled their definitions. Most participants hoped to decrease the symptoms of their disease or to improve their functional ability. Their goals were reflected in the program's goals; however, the definition of health held by the multidisciplinary team directing the program was broader than those expressed by most participants. PMID- 8516257 TI - Blood pressure comparison in a selected Native American and white population. AB - This study compared the frequency of blood pressure elevation in a selected Native American and white population. Three hundred individuals participated: 87 Native Americans, 210 whites, and 3 others. Data were gathered using a questionnaire that addressed residence, sex, age, race, occupation, height, smoking, alcohol use, tea/coffee consumption, medications, and past or present illness. Weight and blood pressure were measured by the researchers at the time of data collection. The sample mean for systolic blood pressure (SBP) was 124 mm Hg (SD 14.78) and diastolic blood pressure (DBP) was 77 mm Hg (SD 10.13). One-way analysis of variance showed age groups and sex to affect blood pressure significantly (P = 0.0001). Stepwise multiple regression indicated weight significantly predicted blood pressure (SBP multiple R = 0.39, P = 0.001; DBP multiple R = 0.43, P = 0.00001). The interaction of age, sex, tobacco, alcohol, and caffeine influenced SBP and DBP. Obviously, these findings have limited generalizeability due to the sampling frame used in this study. PMID- 8516258 TI - Job satisfaction of rural public and home health nurses. AB - Based on Vroom's expectancy theory, this study was conducted to identify differences in job satisfaction between nurses working in public health settings, and staff nurses and administrators working in both settings. Questionnaires containing an adaptation of a job satisfaction scale were mailed to all 258 registered nurses practicing in public health and home health settings (response rate 57%) in a rural midwestern state. Respondents were asked to rate their satisfaction with various dimensions of their jobs, as well as how important each aspect was to them. Although both groups of nurses reported low satisfaction with salary, public health nurses were significantly less satisfied with their salaries than were home health nurses (F = 32.96, P < or = 0.001); home health nurses, however, were significantly less satisfied with benefits/rewards (F = 11.85, P < or = 0.001), task requirements (F = 8.37, P < or = 0.05), and professional status (F = 5.30, P < or = 0.05). Although administrators did not differ significantly from staff nurses on job satisfaction, they did perceive organizational climate (F = 4.50, P < or = 0.05) to be an important feature of satisfaction. These differences may be partially explained by divergent salaries, roles, and responsibilities between public health and home health nurses. PMID- 8516259 TI - Effects of public health nursing participation in selected academic courses on self-reported functions and competencies: a collaborative pilot study. AB - A profile of the education levels of practicing public health nurses (PHNs) in Mississippi in 1988 indicated that 71% of those nurses were prepared in associate degree or diploma programs. Since these programs typically do not provide formal academic courses in community health nursing, nurses currently enter the workplace with insufficient preparation for this increasingly complex role. A collaborative pilot study between the agency and a state-supported school of nursing evaluated the impact of participating in selected components of an academic community health nursing program on the self-reported competencies and functions of beginning PHNs. Twelve PHNs who were employed during six months in the geographic area contiguous to the school were selected to attend 10 classroom sessions on basic topics applicable to the generic PHN role in a southern state. A control group of 12 PHNs hired during the same period of time was also selected. Both groups completed an instrument on functions and competencies before and after the course. A significant difference was seen in certain functions and competencies between attenders and nonattenders. PMID- 8516260 TI - Public health nursing and the Jewish contribution. PMID- 8516261 TI - Nursing and the community. 1938. PMID- 8516262 TI - One hundred years of powerful women: a conversation with Ione Carey. Interview by Sherry Shamansky. PMID- 8516263 TI - Effects of L and D-carnitine on brain energy metabolites in mice given sublethal doses of ammonium acetate. AB - Previous studies in our laboratory have shown that L-carnitine suppresses seizures and alterations of brain energy metabolism in mice caused by hyperammonemia. The present study was done to exclude the effects of seizures on brain energy metabolism. When sublethal dose of ammonium acetate (12 mmol/kg b.wt.) was injected to mice, all mice survived without developing seizures, while clear increase of brain ammonia and alterations of brain energy metabolites were seen. In L-carnitine-treated animals, the levels of ammonia, AMP and lactate were lower and those of ATP and phosphocreatine were higher than in untreated animals. Treatment with D-carnitine also preserved the phosphocreatine level. This indicates that the improvement of brain energy metabolism by L-carnitine in hyperammonemia is not simply a result of the suppression of seizures, and that the "physiological" function of carnitine may not be the sole mechanism underlying this effect. PMID- 8516264 TI - Effect of lovastatin on cholesterol absorption in cholesterol-fed rabbits. AB - The aim of the present study was to investigate the effect of the hydroxymethylglutaryl (HMG)-CoA reductase inhibitor lovastatin on some aspects of cholesterol metabolism in cholesterol-fed rabbits. The plasma cholesterol concentration was markedly lower in lovastatin-treated rabbits (6 mg/rabbit/day) compared to controls after 36 days of cholesterol-feeding (x +/- S.E.) (19 +/- 4 mmol/l, n = 9 versus 153 +/- 17 mmol/l, n = 7) (P < 0.00001). Intestinal absorption of cholesterol in such rabbits was reduced by 15% in lovastatin treated rabbits (n = 21) compared to controls (n = 18) (P < 0.025). The results suggest that the hypocholesterolaemic effect of lovastatin in cholesterol-fed rabbits is associated with a decreased intestinal absorption of cholesterol. PMID- 8516265 TI - Binding of [3H]SCH 39166 to human post mortem brain tissue. AB - The dopamine D1 antagonist SCH 39166 was labelled with tritium and used for in vitro binding and autoradiography using human post mortem brain tissue. Competition studies on tissue from human nucleus caudatus showed that SCH 23390 inhibited the binding of [3H]SCH 39166 biphasically. The non-specific binding of [3H]SCH 39166 in both nucleus caudatus and cerebellum was lower after the addition of SCH 23390 or SCH 39166 than after flupentixol (10 microM). Autoradiography showed specific [3H]SCH 39166 binding in the caudate nucleus and putamen in the brain sections. The binding of [3H]SCH 39166 in the medial part of the caudate nucleus was very dense and similar to that obtained with [3H]SCH 23390, which was used as a reference ligand. Dense binding of [3H]SCH 39166 was also found in cortical regions, and binding was also obtained in the cerebellum and in the hippocampus. Addition of flupentixol (10 microM) abolished some but not all the binding of [3H]SCH 39166. The binding of [3H]SCH 39166 to caudate and putamen was not totally abolished by the addition of excess SCH 23390, while excess SCH 39166 diminished the binding of [3H]SCH 23390 in all regions. The present study indicates that [3H]SCH 39166, similar to [3H]SCH 23390, binds to dopamine D1 receptors in the human brain. It is concluded that [3H]SCH 39166 has a slightly different binding pattern than [3H]SCH 23390, which can be due to labelling of one or two additional binding site(s) pharmacologically unrelated to dopamine D1 receptors. PMID- 8516266 TI - Ventilation, CO2 production, and CO2 exposure effects in conscious, restrained CF 1 mice. AB - Respiratory rate (f), tidal volume (VT) and carbon dioxide production (VECO2) were measured in restrained, conscious CF-1 mice. Mean f +/- S.D. and mean VT +/- S.D. were 270 +/- 8 breaths/min. and 0.123 +/- 0.024 ml (STPD) for male, and 274 +/- 15 breaths/min. and 0.115 +/- 0.023 ml (STPD) for female mice, respectively. VECO2 was obtained from a rebreathing (closed loop) system. The maximum VECO2 (STPD) amounted to 95.5 +/- 15.4 ml/(kg min.) in males and to 72.7 +/- 4.2 ml/(kg min.) in females. The CO2 concentration in the closed loop system increased slowly during a 30 min. rebreathing period and reached a concentration of about 2.7%. No effect was seen on f and on VT. Dynamic (abrupt) exposure up to 10.3% CO2 had no effect on f in male mice, whereas VT increased from 112% (2.3% CO2) to 181% (10.3% CO2). The estimated O2 concentrations decreased from 20.5% to 18.7% with increasing CO2 exposure. The equivalent CO2 experiments with O2 kept at 16% by N2 administration showed that the lower O2 concentration added an additional drive on the respiratory centre. PMID- 8516268 TI - [Pathology--availability and utilization]. PMID- 8516267 TI - Relationship between circulating vitamin D3 metabolites and prolactin or growth hormone levels in rat. AB - Previous studies (Haug & Gautvik 1985) have demonstrated specific receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a clonal (GH3) strain of rat pituitary tumour cells. It was discovered that 1,25(OH)2D3 affected the production of prolactin and growth hormone in these cells in a calcium dependent manner. These findings were the basis for a hypothesis that vitamin D3 could be involved in the regulation of pituitary hormones in vivo. To further investigate this contention, female rats were given subcutaneous injections of 1,25(OH)2D3, 25-hydroxyvitamin D3 (25(OH)D3) or 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) three times a week for up to 12 weeks. Blood samples were withdrawn after 28, 56 and 84 days of treatment and analysed for vitamin D3 metabolites, prolactin and growth hormone, and serum ionized (free) and total calcium (Ca). Between treatment group comparisons of serum prolactin and growth hormone levels did not show significant vitamin D3 induced alterations. However, correlation matrix analyses on all variables revealed that serum level of growth hormone was significantly (P < 0.05) and inversely related to corresponding total Ca. Prolactin, on the other hand, may be subject to a complex regulation by 1,25(OH)2D3 and free Ca2+. PMID- 8516269 TI - [Idiopathic asymmetric heart hypertrophy in a newborn infant]. AB - A sporadic case of idiopathic asymmetric heart hypertrophy in a newborn infant is reported. Despite drug therapy the baby died in progressive heart failure at 23 days of age. At necropsy there was cardiac hypertrophy with features similar to those of the usual asymmetric from observed in adults. On gross examination the myocardium of the ventricular septum and the free wall of the left ventricle showed a disorganized structure. Microscopically, the changes consisted of an abnormal arrangement of muscle cells and muscle bundles with areas of hypertrophied myofibers. In agreement with other authors myocardial disorganization ("disarray") is interpreted as a form of dysplasia, hypertrophy being a secondary phenomenon. The hypothesis that these abnormalities represent the persistence of the embryonic myocardial structure is discussed. The pathogenetic significance of focal myocardial dysplasias is apparently related to the amount of myocardium involved. PMID- 8516270 TI - [Histologic findings on the pathogenesis of corpus gastritis]. PMID- 8516271 TI - [Von Hippel-Lindau syndrome]. PMID- 8516272 TI - [Fulminant streptococcal myositis]. PMID- 8516273 TI - [Fatal genetic-morphologic syndromes. The campomelic syndrome]. PMID- 8516274 TI - [Fatal genetic-morphologic syndromes. Fatal pterygium syndrome]. PMID- 8516275 TI - [Bronchial cyst in the endocardium of the left heart. Case report with review of cardiac heterotopic tissues]. AB - Connatal heterotopies are rare accidental findings fore-most without clinical symptoms. The present case report describes an asymptomatic multilocular bronchial cyst of a 72 years old woman which occurred in the left ventricular endocard of the anterior papillary muscle and which was covered with ciliated and occasionally multilayered epithelium. Today the knowledge about these rare cardial heterotopies is important, because they are not only accidental postmortal findings but also the clinical importance is rising as consequence of the improved diagnostic imaging procedures with a high resolution. The histogenesis and the classification of cardial heterotopies is discussed. PMID- 8516276 TI - [Arvid Lindau on his 100th birthday]. PMID- 8516278 TI - [The immobilization of proteolytic enzymes on carbon materials]. AB - Immobilization of proteolytic enzymes on carbon materials depends on the concentration of the protein to be immobilized, the protein/carrier ratio and pH. The kinetics of the proteolytic enzyme adsorption and combined immobilization of proteases and lytic enzymes are considered, and properties of the resultant preparations (temperature and pH optima) and the effect of gamma-sterilization are discussed. Chymotrypsin and terrilytin immobilized on carbon SKN-2P hydrolysed 0.2% solution of casein during 25-27 days with a maximum yield of 50 70%. PMID- 8516277 TI - [Laccase from Coriolus hirsutus--a new marker enzyme for immunoenzyme analysis]. AB - A new immunochemical reagent is proposed which contains laccase, isolated from the culture liquid of the basidial fungus Coriolus hirsutus, as a marker enzyme. The feasibility of immunolaccase conjugates for different variants of immunoassay, i.e. "sandwich", competitive and indirect, is demonstrated. The comparison of immunolaccase and immunoperoxidase conjugates showed that the absolute sensitivity of laccase-antibody conjugates was 3 times higher than that of antibody-peroxidase conjugates (7.7 x 10(-11) M and 2.3 x 10(-10) M, respectively). The assay based on antibody-laccase conjugates is simpler than that employing antibody-peroxidase conjugates, since in the former case air oxygen in used as the second substrate of the enzymatic reaction. PMID- 8516279 TI - [The purification and properties of an extracellular sialo-specific lectin of Bacillus subtilis 316M]. AB - A simple procedure is proposed for purification of lectin from the culture liquid of non-pathogenic Bacillus subtilis 316M, which includes fractionation with ammonium sulfate and rechromatography on Sepharose CL-6B. The procedure enables a 213-fold purification of lectin with a specific activity of 2560 U/mg protein and 51% recovery in activity. According to gel-filtration through Sepharose the lectin has a molecular weight of 190 kDa. It consists of two types of subunits with hemagglutinating activity. The lectin is highly specific to N glycolylneuraminic and N-acetylneuraminic acids and fructose 1.6-biphosphate. PMID- 8516280 TI - [The resistance of liposomes as potential drug carriers to the action of phospholipase A2]. AB - Stability of liposomes with varied phospholipid (PL) content towards the action of phospholipase A2 (PLA2) was studied in vitro. Liposomes were prepared of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) and their mixtures with sphingomyelin (SM). PC and PG liposomes were also treated with PLA2 in the presence of a number of proteins such as cytochrome c, cytochrome b5, cytochrome P-450, polylysine, and histone H1. Among all the liposomes studied PG-containing ones were found to be most stable towards PLA2. In SM-containing liposomes, the levels of PG, PI, PE and PC after 20 min of hydrolysis were 65, 62, 55 and 50%, respectively. In PC + PG liposomes, the PC content after treatment with PLA2 was by about 15-20% higher than in control PC liposomes. The addition of all the proteins studied influenced significantly stability of both PC and PG in two-component PL liposomes, but had no effect on liposomes consisting only of PC. The incorporation of the integral membrane protein cytochrome P-450 into PC and PG liposomes caused a decrease in their stability towards PLA2, the decrease depending on the lipid/protein molar ratio. PMID- 8516281 TI - Oscillating molecules and how they move circadian clocks across evolutionary boundaries. PMID- 8516282 TI - Gaucher disease as a paradigm of current issues regarding single gene mutations of humans. AB - Gaucher disease is a glycolytic storage disease caused by a deficiency in activity of the catabolic enzyme glucocerebrosidase. Over 35 different mutations have been documented, including missense and nonsense point mutations, splicing mutations, deletions and insertions, a fusion gene, and examples of gene conversion. Gaucher disease is most common in the Ashkenazi Jewish population, in which just five of the mutations in this population account for 98% of the disease-producing alleles. Each of these mutations is found in the context of a single haplotype, a finding consistent with a single origin of each mutation. Although it is clear that these mutations provide a selective advantage in the Jewish population and thus constitute a balanced polymorphism, the nature of the advantage is unknown. Gaucher disease can be treated symptomatically, by administration of the missing enzyme, by allogeneic bone marrow transplantation, and potentially by gene transfer into hematopoietic stem cells. Increasing understanding of this disease has, as in other genetic disorders, created a host of social and ethical dilemmas regarding matters such as the cost of treatment for rare diseases and the advantages and disadvantages of population-targeted genetic screening. PMID- 8516283 TI - Phosphorylation of the regulatory subunit of type II beta cAMP-dependent protein kinase by cyclin B/p34cdc2 kinase impairs its binding to microtubule-associated protein 2. AB - Subcellular localization of type II cAMP-dependent protein kinase is determined by the interactions of the regulatory subunit (RII) with specific RII-anchoring proteins. By using truncated NH2-terminal RII beta fusion proteins expressed in Escherichia coli and the mitotic protein kinase p34cdc2 isolated from HeLa cells or starfish oocytes, we investigated the in vitro phosphorylation of RII beta by these kinases. The putative site for phosphorylation by the mitotic kinases is Thr-69 in the NH2-terminal domain of RII beta. This phosphorylation site matches the consensus sequence X(T/S)PX(K/R) for p34cdc2 recognition and belongs to a well-conserved sequence found in all RII beta sequences known to date. In contrast to phosphorylation by casein kinase II or the cAMP-dependent protein kinase catalytic subunit, phosphorylation of RII beta by mitotic kinases impaired its interaction with a well-known RII-anchoring protein, the neuronal microtubule associated protein 2. The potential regulatory significance of the phosphorylation of this site on the interaction with microtubule-associated protein 2 and other RII-anchoring proteins and the physiological relevance of this cyclin B/p34cdc2 kinase-catalyzed modification of RII beta (or phosphorylation by other proline-directed protein kinases) are discussed. PMID- 8516284 TI - A double-filter method for nitrocellulose-filter binding: application to protein nucleic acid interactions. AB - Nitrocellulose-filter binding is a powerful technique commonly used to study protein-nucleic acid interactions; however, its utility in quantitative studies is often compromised by its lack of precision. To improve precision and accuracy, we have introduced two modifications to the traditional technique: the use of a 96-well dot-blot apparatus and the addition of a DEAE membrane beneath the nitrocellulose membrane. Using the dot-blot apparatus, an entire triplicate set of data spanning 20-24 titrant concentrations can be collected on a single 4.5 x 5 inch sheet of nitrocellulose, obviating the need to manipulate separate filters for each titration point. The entire titration can then be quantitated simultaneously with direct two-dimensional beta-emission imaging technology. The DEAE second membrane traps all DNA that does not bind to the nitrocellulose, enabling a direct determination of the total amount of DNA filtered. This measurement improves precision by allowing the amount of DNA retained by the nitrocellulose to be normalized against the total amount of DNA filtered. The DEAE membrane also permits a more accurate quantitation of filter-retention efficiency and nonspecific background retention based on free DNA rather than total DNA filtered. The general approach and methods of analysis to obtain equilibrium binding isotherms are discussed, using as examples our studies of the Escherichia coli Rep protein, a helicase, and its interactions with short oligodeoxynucleotides. PMID- 8516286 TI - Electron self-exchange in azurin: calculation of the superexchange electron tunneling rate. AB - Electronic coupling between the copper atoms in an azurin dimer has been calculated in this conformationally well-defined system by using many-electronic wave functions. When one of the two water molecules forming intermolecular hydrogen bonds between the copper-ligating His-117 of the two azurins is removed, the calculated coupling element is reduced from 2.5 x 10(-6) to 1.1 x 10(-7) eV (1 eV = 1.602 x 10(-19) J). Also, the effects of the relative orientations of the two water molecules have been analyzed. The results show that water molecules may play an important role as switches for biological electron transfer. The rate of electron self-exchange between two azurins has been calculated, and the result is in very good agreement with the rate found experimentally. PMID- 8516285 TI - Yeast DNA-repair gene RAD14 encodes a zinc metalloprotein with affinity for ultraviolet-damaged DNA. AB - Xeroderma pigmentosum (XP) patients suffer from a high incidence of skin cancers due to a defect in excision repair of UV light-damaged DNA. Of the seven XP complementation groups, A-G, group A represents a severe and frequent form of the disease. The Saccharomyces cerevisiae RAD14 gene is a homolog of the XP-A correcting (XPAC) gene. Like XP-A cells, rad14-null mutants are defective in the incision step of excision repair of UV-damaged DNA. We have purified RAD14 protein to homogeneity from extract of a yeast strain genetically tailored to overexpress RAD14. As determined by atomic emission spectroscopy, RAD14 contains one zinc atom. We also show in vitro that RAD14 binds zinc but does not bind other divalent metal ions. In DNA mobility-shift assays, RAD14 binds specifically to UV-damaged DNA. Removal of cyclobutane pyrimidine dimers from damaged DNA by enzymatic photoreactivation has no effect on binding, strongly suggesting that RAD14 recognizes pyrimidine(6-4)pyrimidone photoproduct sites. These findings indicate that RAD14 functions in damage recognition during excision repair. PMID- 8516287 TI - Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. AB - The Enhancer of split [E(spl)] gene complex belongs to the class of neurogenic loci, which, in a concerted action, govern neurogenesis in Drosophila. Two genetically distinct functions, vital and neurogenic, reside within the complex defined by lethal mutations in the l(3) gro gene and by the typical neurogenic phenotype of deletions, respectively. Such deletions always affect several of the many embryonically active genes in the region, which cannot be mutated separately to lethality. Seven of these genes are extremely similar at the transcription and sequence level sharing the basic helix-loop-helix (bHLH) motif of transcriptional regulators. While these E(spl) bHLH genes seem to be required collectively for neurogenesis, they are nonessential individually, suggesting functional redundancy of the encoded gene products. No specific functions could yet be ascribed to any of the other genes located within the complex. One might expect these apparently dispensable genes, as well as the supposedly redundant bHLH genes, to be under little evolutionary constraint and, thus, to evolve most rapidly. However, we find the entire E(spl) gene complex highly conserved during Drosophila evolution, indicating that all the genes as well as their organization are of functional importance. PMID- 8516288 TI - On the directional specificity of ribosome frameshifting at a "hungry" codon. AB - Limitation for aminoacyl-tRNA promotes ribosome frameshifting at certain sites. We have previously demonstrated ribosome frameshifting to the right (3') at an AAG site in one context, and to the left (5') at an AAG site in a different context. Here, we demonstrate that the "rightwing" context is largely specific for frameshifting to the right, and the "leftwing" context is largely specific for frameshifting to the left. Analysis of these context rules, and the conversion of a sequence that promotes leftward frameshifting to one that promotes rightward frameshifting, demonstrated here, permits us to define a minimal heptanucleotide sequence sufficient for shiftiness in each direction at an AAG codon whose lysyl-tRNA is in short supply. PMID- 8516289 TI - Cloning of the STE5 gene of Saccharomyces cerevisiae as a suppressor of the mating defect of cdc25 temperature-sensitive mutants. AB - The STE5 gene of Saccharomyces cerevisiae was cloned using a screening procedure designed to isolate genes of the S. cerevisiae pheromone response pathway. We screened a yeast genomic high-copy-number plasmid library for genes that allow mating of cdc25ts mutants at the restrictive temperature without affecting the cell-cycle-arrest phenotype. One of the genes cloned was identified by genetic analysis as STE5. STE5 encodes a predicted open reading frame of 916 amino acids and exhibits significant homology to Far1 protein. RNA blot analysis reveals that STE5 gene transcription is regulated by the mating type of the cell and depends on an intact pheromone-response pathway. PMID- 8516290 TI - Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. AB - Loss of a whole chromosome 5 or a deletion of its long arm (5q) is a recurring abnormality in malignant myeloid neoplasms. To determine the location of genes on 5q that may be involved in leukemogenesis, we examined the deleted chromosome 5 homologs in a series of 135 patients with malignant myeloid diseases. By comparing the breakpoints, we identified a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. Distal 5q contains a number of genes encoding growth factors, hormone receptors, and proteins involved in signal transduction or transcriptional regulation. These include several genes that are good candidates for a tumor-suppressor gene, as well as the genes encoding five hematopoietic growth factors (CSF2, IL3, IL4, IL5, and IL9). By using fluorescence in situ hybridization, we have refined the localization of these genes to 5q31.1 and have determined the order of these genes and of other markers within 5q31. By hybridizing probes to metaphase cells with overlapping deletions involving 5q31, we have narrowed the critical region to a small segment of 5q31 containing the EGR1 gene. The five hematopoietic growth factor genes and seven other genes are excluded from this region. The EGR1 gene was not deleted in nine other patients with acute myeloid leukemia who did not have abnormalities of chromosome 5. By physical mapping, the minimum size of the critical region was estimated to be 2.8 megabases. This cytogenetic map of 5q31, together with the molecular characterization of the critical region, will facilitate the identification of a putative tumor-suppressor gene in this band. PMID- 8516291 TI - Variant-specific surface proteins of Giardia lamblia are zinc-binding proteins. AB - Giardia lamblia undergoes surface antigenic variation. The variant-specific surface proteins (VSPs) are a distinct family of cysteine-rich proteins. Characteristically, cysteine residues occur mostly as CXXC tetrapeptides. Four of the reported five VSPs contain a putative metal-binding domain that resembles other metal-binding motifs; the fifth is closely related but lacks an essential histidine. Three different native VSPs bound Zn2+. Co2+, Cu2+, and Cd2+ inhibited Zn2+ binding. Analysis of recombinant VSP fusion proteins showed that the putative binding motif bound Zn2+. Surprisingly, peptide fragments from other regions of the VSP contain numerous CXXCXnCXXC motifs that also bound Zn2+. Analysis of deduced amino acid sequences showed well-conserved CXXC spacing in three out of five VSPs, suggesting conservation of structure despite amino acid sequence divergence. The function of VSPs is unknown, but by binding Zn2+ or other metals in the intestine, VSPs may contribute to Zn2+ malnutrition or inhibition of metal-dependent intestinal enzymes, which would lead to malabsorption, a well-known consequence of giardiasis. PMID- 8516292 TI - Simulation of human autosomal dominant retinitis pigmentosa in transgenic mice expressing a mutated murine opsin gene. AB - Autosomal dominant retinitis pigmentosa (ADRP), slowly progressing over decades, leads to severe visual impairment and in some cases to complete blindness. More than 40 mutations in the human opsin gene have been linked to some forms of this genetically heterogeneous disease. In photoreceptor cells of ADRP patients with mutations in the opsin gene, normal rhodopsin is thought to be synthesized concomitantly with mutated rhodopsin, which, by an unknown mechanism, causes the slow degeneration of the photoreceptor cells. To establish a transgenic mouse line that carries a mutated mouse opsin gene in addition to the endogenous opsin gene, we introduced a mouse opsin gene containing mutations in exon 1 into the germ line of a normal mouse. The alterations consisted of three amino acid substitutions near the N terminus of rhodopsin, Val-20-->Gly (V20G), Pro-23-->His (P23H), and Pro-27-->Leu (P27L). The P23H mutation is the most prevalent mutation in human ADRP patients. During early postnatal development, mice heterozygous for the mutated opsin gene appear to develop normal photoreceptors, but their light sensitive outer segments never reach normal length. With advancing age, both rod and cone photoreceptors are reduced progressively in number. The slow degeneration of the transgenic retina is associated with a gradual decrease of light-evoked electroretinogram responses. Our results show that simultaneous expression of mutated and normal opsin genes induces a slow degeneration of both rod and cone photoreceptors and that the course of the retinal degeneration of the mutant mouse retina mimics the course of human ADRP. PMID- 8516293 TI - The 110-kDa polypeptide of spinach plastid DNA-dependent RNA polymerase: single subunit enzyme or catalytic core of multimeric enzyme complexes? AB - Highly purified RNA polymerase preparations from spinach chloroplasts contain seven major polypeptides of 150, 145, 110, 102, 80, 75, and 38 kDa. I find that RNA polymerase activity can be separated under defined conditions into three different fractions by heparin-Sepharose chromatography. Immunological analysis has shown that the first fraction contains RNA polymerase activity associated with all seven major polypeptides, and other studies have shown that some of these polypeptides (150, 145, 80, and 38 kDa) are associated with an RNA polymerase similar to the Escherichia coli enzyme. However, similar analyses of the remaining fractions show activity associated only with the 110-kDa polypeptide, suggesting the existence of a second kind of chloroplast RNA polymerase. Samples of this 110-kDa polypeptide purified by SDS/PAGE actively synthesize RNA in a reaction dependent on a supercoiled DNA template and the four ribonucleoside triphosphates. Hence, this polypeptide has all of the properties expected of a single-subunit RNA polymerase of the T7 bacteriophage type. PMID- 8516294 TI - A motility in the eukaryotic flagellum unrelated to flagellar beating. AB - We report a motility in the flagella of the green alga Chlamydomonas that is unrelated to dynein-based flagellar beating. This motility, referred to as intraflagellar transport, was observed as the rapid bidirectional movement of granule-like particles along the length of the flagella. Intraflagellar transport could be experimentally separated from other, previously reported, nonbeat flagellar motilities. EM of flagella showed groups of nonvesicular, lollipop shaped structures positioned between the outer doublet microtubules and the flagellar membrane. Movement of these complexes along the length of the flagella may be responsible for intraflagellar transport. PMID- 8516296 TI - Genetic evidence for replication enhancement from a distance. AB - Rolling circle replication of the Staphylococcus aureus plasmid pT181 requires interaction of the RepC initiator protein with the origin of replication (the ori site). A second site named cmp, which is distant from ori, is thought to stimulate replication, since a mutant pT181 plasmid lacking cmp cannot coexist with a cmp+ wild-type plasmid. Second-site mutations compensating for the loss of cmp were shown to map in repC. The compensatory mutations produced RepC proteins that, unlike the wild-type, either failed to discriminate between cmp+ and cmp- plasmids or preferred cmp- to cmp+ plasmids. These studies demonstrate that cmp stimulates the interaction of the replication initiator protein with the origin and therefore enhances DNA replication from a distance. PMID- 8516295 TI - Interactions between three common subunits of yeast RNA polymerases I and III. AB - The AC40 and AC19 subunits (encoded by RPC40 and RPC19) are shared by yeast RNA polymerases I and III and have a local sequence similarity to prokaryotic alpha subunits. Mutational analysis of the corresponding "alpha motif" indicated that its integrity is essential on AC40 subunit but is not essential on AC19 subunit. By applying the two-hybrid method, these two polypeptides were shown to associate in vivo. Extragenic suppression of rpc19 and rpc40 mutations confirmed that AC19 and AC40 subunits interact with each other in vivo and revealed an interaction with ABC10 beta subunit [encoded by RPB10; Woychick, N. A. & Young, R.A. (1990) J. Biol. Chem. 265, 17816-17819], one of the five polypeptides common to all three nuclear RNA polymerases. A correction of the RPB10 sequence showed that ABC10 beta subunit is a 70-amino acid polypeptide, as confirmed by peptide microsequencing. These results suggest that the assembly of RNA polymerase I and III requires the association of ABC10 beta subunit with an AC19/AC40 heterodimer. PMID- 8516297 TI - Conservation of genetic information: a code for site-specific DNA recognition. AB - We present findings of genetic information conservation between the glucocorticoid response element (GRE) DNA and the cDNA encoding the glucocorticoid receptor (GR) DNA-binding domain (DBD). The regions of nucleotide sub-sequence similarity to the GRE in the GR DBD occur specifically at nucleotide sequences on the ends of exons 3,4, and 5 at their splice junction sites. These sequences encode the DNA recognition helix on exon 3, a beta-strand on exon 4, and a putative alpha-helix on exon 5, respectively. The nucleotide sequence of exon 5 that encodes the putative alpha-helix located on the carboxyl terminus of the GR DBD shares sequence similarity with the flanking nucleotide regions of the GRE. We generated a computer model of the GR DBD using atomic coordinates derived from nuclear magnetic resonance spectroscopy to which we attached the exon 5 encoded putative alpha-helix. We docked this GR DBD structure at the 39-base-pair nucleotide sequence containing the GRE binding site and flanking nucleotides, which contained conserved genetic information. We observed that amino acids of the DNA recognition helix, the beta-strand, and the putative alpha-helix are spatially aligned with trinucleotides identical to their cognate codons within the GRE and its flanking nucleotides. PMID- 8516298 TI - Inactivation of the NF1 gene in human melanoma and neuroblastoma cell lines without impaired regulation of GTP.Ras. AB - The NF1 gene, which is altered in patients with type 1 neurofibromatosis, encodes neurofibromin, a protein whose GTPase-activating function can negatively regulate GTP-Ras by accelerating its conversion to inactive GDP-Ras. In schwannoma cell lines from patients with neurofibromatosis, loss of neurofibromin was previously shown to be associated with impaired regulation of GTP-Ras. Our analysis of other neural crest-derived tumor cell lines has shown that some melanoma and neuroblastoma cell lines established from tumors occurring in patients without neurofibromatosis contain reduced or undetectable levels of neurofibromin, with concomitant genetic abnormalities of the NF1 locus. In contrast to the schwannoma cell lines, GTP-Ras was appropriately regulated in the melanoma and neuroblastoma lines that were deficient in neurofibromin, even when c-H-ras was overexpressed in the lines. These results demonstrate that some neural crest tumors not associated with neurofibromatosis have acquired somatically inactivated NF1 genes and suggest a tumor-suppressor function for neurofibromin that is independent of Ras GTPase activation. PMID- 8516299 TI - CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals. AB - PCR was used to clone isolates of the human immunodeficiency virus type 1 (HIV-1) nef gene directly from peripheral blood leukocytes of HIV-1-infected individuals. A transient expression system with human CEM T cells was used to assess the effect of nef on CD4 antigen expression on the cell surface. We show that CD4 down-regulation is a frequent property of primary HIV-1 nef alleles. Mutations in conserved amino acid motifs of Nef disrupted CD4 down-regulation. Our observations strongly suggest that CD4 down-regulation reflects a conserved function of nef, which is selected in vivo in human HIV-1 infection. Methodology described here provides quantitative assays to establish whether alterations in nef correlate with the dynamics of disease progression in human AIDS. PMID- 8516300 TI - Formins: phosphoprotein isoforms encoded by the mouse limb deformity locus. AB - Mutations at the mouse limb deformity (ld) locus result in defects of growth and patterning of the limb and kidney during embryonic development. The gene responsible for this phenotype is large and complex, with the capacity to generate a number of alternatively spliced messenger RNA transcripts encoding nuclear protein isoforms called "formins." We have made polyclonal antibodies to specific formin peptides and have confirmed the authenticity of the antibodies' reactivity, using cell lines derived from mice with molecularly defined mutations at the ld locus. In addition, we have used these antibodies to detect and characterize polypeptides encoded by both wild-type and mutant ld alleles. In so doing, we show that a formin isoform (i) is modified by posttranslational phosphorylation at serine and threonine residues and (ii) when present in a crude nuclear extract, is retained by DNA-cellulose. PMID- 8516301 TI - Characterization of the mouse gene that encodes the delta/YY1/NF-E1/UCRBP transcription factor. AB - The mouse gene that encodes the delta transcription factor has been cloned and characterized. This gene spans 23 kb and is composed of five exons and four introns. The first exon consists of a long (431 bp), (C+G)-rich, untranslated segment and a 679-bp coding segment, which specifies the unusual tracts of consecutive acidic residues and histidines and the long alanine-glycine stretches. The sequence that encodes the four zinc-finger motifs of this protein is interrupted by two introns. Nuclease protection experiments revealed a major transcriptional start point and several additional start points distributed over a 28-bp segment. Transfection experiments with 5' and 3' deletion mutants localized the promoter to a (C+G)-rich region that is < 700 bp upstream and no more than 32 bp downstream of the major start point. An especially critical promoter element lies between -58 and -18 and contains a high-affinity Sp1 binding site, as demonstrated by electrophoretic mobility-shift experiments with nuclear extract and recombinant Sp1 proteins. Several striking similarities between the delta gene and genes encoding other transcription factors and regulatory proteins are noted and discussed with respect to their possible biological significance. PMID- 8516302 TI - Residues crucial for Ras interaction with GDP-GTP exchangers. AB - Cdc25 is essential for Ras-mediated activation of adenylyl cyclase in the yeast Saccharomyces cerevisiae. This protein acts by catalyzing GDP-GTP exchange on yeast Ras. Harvey (Ha) ras expressed in S. cerevisiae is also recognized by both Cdc25 and Sdc25, a yeast homolog of Cdc25. Thus it is feasible to examine molecular aspects of mammalian Ras modulation by Cdc25 using the RAS/cAMP pathway in yeast as a model system. Here, we describe mutational analysis of Ha-ras for the identification of residues critical for the ability of Ras to interact with Cdc25 and related guanine nucleotide-release proteins. Mutations within codons 97 108 impaired Ras-mediated activation of adenylyl cyclase in the presence but not in the absence of mammalian GTPase-activating protein. Such mutations, therefore, affected the ability of Ras to undergo GDP-GTP exchange catalyzed by the guanine nucleotide exchanger without preventing Ras activation of the effector. Similar mutations were previously shown to impair the ability of c-ras to transform mammalian cells while having a less drastic effect on v-ras. PMID- 8516303 TI - Molecular cloning and adhesive properties of murine platelet/endothelial cell adhesion molecule 1. AB - We describe the isolation and characterization of a functional murine platelet/endothelial cell adhesion molecule (PECAM) 1 cDNA clone from a mouse lung library. At the nucleotide level, the coding sequence of murine PECAM-1 is 73% identical to human PECAM-1, and at the amino acid level, the sequence is 79% homologous to its human counterpart. Southern hybridization reveals that one copy of the gene exists in the mouse genome; Northern hybridization reveals a single mRNA species in mouse lung tissue. COS-7 and mouse L cells transfected with murine PECAM-1 expressed a 130-kDa glycoprotein on their surfaces that reacted with anti-murine PECAM-1 monoclonal antibody and comigrated on SDS/PAGE with human PECAM-1. Stable L-cell transfectants aggregate with each other in a PECAM dependent, homophilic manner. PMID- 8516304 TI - A molecular phylogeny for marine turtles: trait mapping, rate assessment, and conservation relevance. AB - Nucleotide sequences from the cytochrome b gene of mitochondrial DNA were employed to resolve phylogenetic controversies and to assess molecular evolutionary rates in marine turtles (Chelonioidea). Findings of special relevance to conservation biology include discovery of a distant relationship between Natator and other cheloniid species, the paraphyly of Chelonia mydas with respect to Chelonia agassizi, and genetic distinctiveness of Lepidochelys kempi from Lepidochelys olivacea. A longstanding debate in evolutionary ecology was resolved by phylogenetic mapping of dietary habits, which indicates that the spongivore Eretmochelys imbricata evolved from a carnivorous rather than a herbivorous ancestor. Sequence divergences at intergeneric and interfamilial levels, when assessed against fossil-based separation times, support previous suggestions (from microevolutionary comparisons) that mitochondrial DNA in marine turtles evolves much more slowly than under the "conventional" vertebrate clock. This slow pace of nucleotide replacement is consistent with recent hypotheses linking substitution rate to generation length and metabolic pace. PMID- 8516305 TI - Unusual charge configurations in transcription factors of the basic RNA polymerase II initiation complex. AB - A systematic analysis of the primary sequences of the polymerase II initiation complex has revealed unusual charge features in the TFII family proteins. In particular, the proteins TFIIA alpha, TFIIE alpha, and TFIIF carry multiple charge clusters and hyper charge runs, sequence features occurring in < 4% of all (available) eukaryotic proteins. Possible implications for these charge structures are discussed in relation to the assembly and function of the polymerase II transcriptional complex. PMID- 8516306 TI - Essential role of the HMG domain in the function of yeast mitochondrial histone HM: functional complementation of HM by the nuclear nonhistone protein NHP6A. AB - The yeast mitochondrial histone protein HM is required for maintenance of the mitochondrial genome, and disruption of the gene encoding HM (HIM1/ABF2) results in formation of a respiration-deficient petite mutant phenotype. HM contains two homologous regions, which share sequence similarity with the eukaryotic nuclear nonhistone protein, HMG-1. Experiments with various deletion mutants of HM show that a single HMG domain of HM is functional and can restore respiration competency to cells that lack HM protein (him1 mutant cells). The gene encoding the putative yeast nuclear HMG-1 homolog, the NHP6A protein, can functionally complement the him1 mutation. These results suggest that the HMG domain is the basic unit for the function of HM in mitochondria and that the function of HMG-1 proteins in the nucleus and HM in the mitochondrion may be equivalent. PMID- 8516307 TI - Plasma viremia as a sensitive indicator of the antiretroviral activity of L 697,661. AB - L-697,661 is a non-nucleoside analogue with potent, selective inhibitory activity against the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1). The present study evaluated the potential role of this compound in the treatment of HIV-1-infected patients in a double-blinded, placebo- and zidovudine controlled trial using plasma viremia as a marker of antiviral activity and real time phenotypic evaluation of viral isolates for the emergence of resistance. Participants received 12 weeks of either placebo, 25 mg twice a day, 100 mg three times a day, or 500 mg twice a day of L-697,661, or zidovudine, 100 mg five times a day. Mean logarithmic reciprocal titers of plasma virus in patients taking either L-697,661 or zidovudine decreased by week 4 of therapy; for L-697,661 recipients these changes were dose-dependent and, at the highest dose tested, were comparable in magnitude to those seen with zidovudine. Viral suppression induced by L-697,661 persisted through 8 weeks of treatment but decreased by week 12. This rebound paralleled emergence of viral isolates showing resistance to L 697,661. We conclude that although L-697,661 has potent antiretroviral activity in vivo, its utility may be compromised by rapid emergence of L-697,661-resistant virus. Plasma viremia is a highly sensitive technique affording considerable utility in the early testing of such agents. PMID- 8516308 TI - Lethality induced by a single site-specific double-strand break in a dispensable yeast plasmid. AB - Cells of the yeast Saccharomyces cerevisiae are delayed in the G2 phase of the cell cycle following chromosomal DNA damage. This arrest is RAD9-dependent and suggests a signaling mechanism(s) between chromosomal lesions and cell cycling. We examined the global nature of growth inhibition caused by an HO endonuclease induced double-strand break (DSB) at a 45-bp YZ sequence (from MAT YZ) in a non yeast region of a dispensable single-copy plasmid. The presence of an unrepaired DSB results in cellular death even though the plasmid is dispensable. Loss of cell viability is partially dependent on the RAD9 gene product. Following induction of the DSB, 40% of RAD+ and 49% of rad9 delta cells [including both unbudded (G1) and budded (S plus G2) cells] did not progress further in the cell cycle. The remaining RAD+ cells progressed to form microcolonies (< 30 cells) containing aberrantly shaped inviable cells. For the rad9 delta mutant, the majority of the remaining cells produced viable colonies accounting for the greater survival of the rad9 delta strain. Based on the profound effects of a single nonchromosomal DNA lesion, this system provides a convenient means for studying the signaling effects of a DNA lesion, as well as for designing strategies for modulating cell proliferation. PMID- 8516309 TI - Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. AB - Random mutagenesis has been used to engineer the protease subtilisin E to function in a highly nonnatural environment--high concentrations of a polar organic solvent. Sequential rounds of mutagenesis and screening have yielded a variant (PC3) that hydrolyzes a peptide substrate 256 times more efficiently than wild-type subtilisin in 60% dimethylformamide. PC3 subtilisin E and other variants containing different combinations of amino acid substitutions are effective catalysts for transesterification and peptide synthesis in dimethylformamide and other organic media. Starting with a variant containing four effective amino acid substitutions (D60N, D97G, Q103R, and N218S; where, for example, D60N represents Asp-60-->Asn), six additional mutations (G131D, E156G, N181S, S182G, S188P, and T255A) were generated during three sequential rounds of mutagenesis and screening. The 10 substitutions are clustered on one face of the enzyme, near the active site and substrate binding pocket, and all are located in loops that connect core secondary structure elements and exhibit considerable sequence variability in subtilisins from different sources. These variable surface loops are effective handles for "tuning" the activity of subtilisin. Seven of the 10 amino acid substitutions in PC3 are found in other natural subtilisins. Great variability is exhibited among naturally occurring sequences that code for similar three-dimensional structures--it is possible to make use of this sequence flexibility to engineer enzymes to exhibit features not previously developed (or required) for function in vivo. PMID- 8516310 TI - Yeast calmodulin and a conserved nuclear protein participate in the in vivo binding of a matrix association region. AB - Chromatin becomes reorganized during mitosis each cell cycle. To identify genes potentially involved in these supramolecular events, we have used a colony-color assay to screen temperature-sensitive mutants of Saccharomyces cerevisiae. When a sequence that mediates attachment to the nuclear matrix in vitro was inserted into the GAL1 promoter of a lacZ fusion gene, beta-galactosidase synthesis was inhibited. This observation permitted screening for temperature-sensitive inducible mutants on 5-bromo-4-chloro-3-indolyl beta-D-galactoside plates. Only 1 of 20 complementation groups of newly isolated mutants exhibited temperature sensitive inducibility for the matrix association region but not for control CEN3 or STE6 inserts--a cmd1 mutant in which the last 7 amino acids of calmodulin were truncated by an ochre termination codon. Another mutant (smi1) exhibited a rare phenotype at the nonpermissive condition, which included S phase and budding arrest. We cloned and sequenced the SMI1 gene, which encodes a 57-kDa polypeptide with evolutionarily conserved epitope(s) found in mammalian cell nuclei. Thus, we provide evidence for involvement of calmodulin and another conserved protein in the in vivo binding of a matrix association region. PMID- 8516311 TI - Delineation of two functional regions of transcription factor TFIIB. AB - Human transcription factor TFIIB, a protein of 316 amino acids, was subjected to limited proteolysis in order to define stable structural domains. We find that the C-terminal region of TFIIB, residues 106-316, is relatively stable, while the N-terminal region is very sensitive to proteases. Like full-length TFIIB, the stable domain, which we refer to as TFIIBc, interacts with the TATA-binding protein (TBP) on DNA. However, TFIIBc is unable to substitute for TFIIB in an in vitro transcription assay. We show by gel mobility-shift experiments that TFIIBc arrests formation of the transcription complex after binding to TBP, and we conclude that the N-terminal region of TFIIB, which is missing from TFIIBc, is responsible for the recruitment of RNA polymerase II to the promoter. We also show that TFIIBc inhibits transcription by competing with full-length TFIIB for the interaction with TBP, either in the presence or in the absence of the TBP associated factors. The acidic transcriptional activator GAL4-VP16 does not favor the assembly of the functional transcription complex over the nonfunctional complex containing TFIIBc. Thus, if the function of GAL4-VP16 is enhancement of the interaction between TFIIB and the TFIID-DNA complex, then this function can also be exerted on the protease-resistant domain TFIIBc. PMID- 8516312 TI - Functional domains of transcription factor TFIIB. AB - Transcription factor TFIIB is an essential component of the RNA polymerase II initiation complex. TFIIB carries out at least two functions: it interacts directly with the TATA-binding protein (TBP) and helps to recruit RNA polymerase II into the initiation complex. The sequence of TFIIB reveals a potential zinc binding domain and an imperfect duplication of approximately 70 amino acids. Mutagenesis of cysteine codons within the putative zinc finger results in mutant proteins that bind normally to TBP but are unable to recruit RNA polymerase II TFIIF into the initiation complex. Changing the two most highly conserved amino acids in the TFIIB repeats reduces the ability of TFIIB to interact with TBP. Therefore, the two functions of TFIIB can be assigned to two separable functional domains of the protein. PMID- 8516313 TI - Functional domains of the AraC protein. AB - The AraC protein, which regulates the L-arabinose operons in Escherichia coli, was dissected into two domains that function in chimeric proteins. One provides a dimerization capability and binds the ligand arabinose, and the other provides a site-specific DNA-binding capability and activates transcription. In vivo and in vitro experiments showed that a fusion protein consisting of the N-terminal half of the AraC protein and the DNA-binding domain of the LexA repressor dimerizes, binds well to a LexA operator, and represses expression of a LexA operator-beta galactosidase fusion gene in an arabinose-responsive manner. In vivo and in vitro experiments also showed that a fusion protein consisting of the C-terminal half of the AraC protein and the leucine zipper dimerization domain from the C/EBP transcriptional activator binds to araI and activates transcription from a PBAD promoter-beta-galactosidase fusion gene. Dimerization was necessary for occupancy and activation of the wild-type AraC binding site. PMID- 8516314 TI - Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. AB - Leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. It has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to Leishmania amazonensis. In this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. In addition to L. amazonensis, trifluralin is effective against Leishmania major and Leishmania tropica, which cause cutaneous infections, Leishmania donovani, which causes visceral disease, Leishmania panamensis, which may cause mucocutaneous infection, and Trypanosoma brucei, an important human and veterinary pathogen. Moreover, most encouragingly, trifluralin is effective in vivo as a topical ointment against L. major and Leishmania mexicana murine cutaneous leishmaniasis. Thus, trifluralin is a promising lead drug for several related, prevalent tropical diseases: leishmaniasis, trypanosomiasis of animals, and, possibly, African trypanosomiasis in humans. PMID- 8516315 TI - Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. AB - Localized 1H NMR spectroscopy in conjunction with J editing was used to measure the concentration of gamma-aminobutyric acid (GABA) in the occipital lobe of four control human volunteers and four epileptic volunteers who were receiving the drug vigabatrin. The GABA concentration measured in four nonepileptic subjects was 1.1 +/- 0.1 mumol/cm3 of brain, which is in good agreement with previous values measured in surgically removed human cortex. A dose-dependent elevation of GABA concentration was measured in patients receiving the GABA transaminase inhibitor vigabatrin, with the maximum measured level of 3.7 mumol/cm3 of brain measured at the highest dose (6 g per day) studied. 1H NMR measurements of GABA in those patients receiving GABA-elevating agents such as vigabatrin will be of importance in establishing the relationship between seizure suppression and the concentration of brain GABA. PMID- 8516316 TI - Extracellular dopamine concentration in the retina of the clawed frog, Xenopus laevis. AB - Dopamine reaches targets in the outer retina of the clawed frog (Xenopus laevis) by diffusion from a network of dopaminergic cells and processes located predominantly at the junction of inner nuclear and inner plexiform layers. We obtained values for the steady-state release, uptake, and extracellular concentration of dopamine in the retina by a combination of HPLC (with electrochemical detection), scintillation spectroscopy, and fast-scan cyclic voltammetry. Vitreal concentrations of dopamine varied from 564 +/- 109 nM in light-adapted eyes near the time of subjective dawn to 156 +/- 12 nM in dark adapted eyes. The data are consistent with a simple model for steady-state dopamine diffusion from an appropriately sited thin-sheet source. This model was used to generate a profile of extracellular dopamine concentration as a function of retinal depth. The model predicted an increase in the dopamine concentration from the vitreous to the layer of dopaminergic cells, remaining constant from that layer to the distal tips of the photoreceptors. This prediction was borne out by comparing fast-scan voltammetric measures of dopamine at the distal tips of the receptors with the vitreal concentrations determined by HPLC using electrochemical detection. PMID- 8516317 TI - Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. AB - We have used a luciferase reporter gene and continuous automated monitoring of bioluminescence to demonstrate unequivocally that cyanobacteria exhibit circadian behaviors that are fundamentally the same as circadian rhythms of eukaryotes. We also show that these rhythms can be studied by molecular methods in Synechococcus sp. PCC7942, a strain for which genetic transformation is well established. A promoterless segment of the Vibrio harveyi luciferase structural genes (luxAB) was introduced downstream of the promoter for the Synechococcus psbAI gene, which encodes a photosystem II protein. This reporter construction was recombined into the Synechococcus chromosome, and bioluminescence was monitored under conditions of constant illumination following entrainment to light and dark cycles. The reporter strain, AMC149, expressed a rhythm of bioluminescence which satisfies the criteria of circadian rhythms: persistence in constant conditions, phase resetting by light/dark signals, and temperature compensation of the period. Rhythmic changes in levels of the native psbAI message following light/dark entrainment supported the reporter data. The behavior of this prokaryote disproves the dogma that circadian mechanisms must be based on eukaryotic cellular organization. Moreover, the cyanobacterial strain described here provides an efficient experimental system for molecular analysis of the circadian clock. PMID- 8516319 TI - Evolution of nest construction in swallows (Hirundinidae): a molecular phylogenetic perspective. AB - Nest construction is more diverse in the Hirundinidae than in any other family of oscine birds. To explore the evolution of this diversity, we superimposed nest data on a DNA-hybridization phylogeny of 17 swallow species. Nest construction is tightly linked to the inferred evolutionary history. Burrowing appears to be the primitive nesting mode, and burrowing ancestors gave rise to cavity-adopting and mud-nesting clades. Obligate cavity adoption is mostly confined to a monophyletic clade in the New World, and the diversification of obligate nest adopters appears to be tied to the richness of forest habitats and recent active mountain building there. Construction of mud nests originated only once in the history of the group, and mud-nesters have diversified principally in Africa, where a drier climatic history has favored their mode of nesting. The use of pure mud to construct a hanging nest is unique among all birds, and we infer that mud nests have increased in complexity during evolution from simple mud cups to fully enclosed retort-shaped nests. This increased complexity appears to have been the critical precursor for the evolution of high-density colonial mud-nesters. PMID- 8516318 TI - Pathogenetic role of Arg-Gly-Asp-recognizing integrins in acute renal failure. off. AB - Reorientation of the alpha 3 subunit of integrins from predominantly basal to the apical cell surface of cultured renal tubular epithelial cells subjected to oxidant stress has previously been demonstrated. The present study was designed to assess functional competence of ectopically expressed apical integrins. Cell cell adhesion assay revealed enhanced cytoatractant properties of stressed cells. Stressed epithelial cells exhibited specific recognition and binding of laminin coated latex beads. These processes were inhibited with the peptide Gly-Arg-Gly Asp-Asn-Pro (GRGDNP) suggesting a role of RGD-recognizing integrins in augmented adhesion to stressed cells. Given that such enhanced adhesion in in vivo acute renal failure may govern tubular obstruction by desquamated epithelium, a physiological marker of patency of tubular lumen, proximal tubular pressure, was monitored in rats subjected to 60 min of renal ischemia followed by reperfusion. Proximal tubular pressure increased 2-fold after 2 hr of reperfusion in animals that had undergone 60 min of ischemia. Infusion of GRGDNP into the renal artery during reperfusion period virtually abolished an increase in proximal tubular pressure observed in ischemic acute renal failure. These in vitro and in vivo findings are consistent with the hypothesis that RGD-recognizing integrins play an important role in the pathogenesis of tubular obstruction in ischemic acute renal failure. PMID- 8516320 TI - Accelerated tumor development in interferon-treated B6.C-Hyal-1 a mice. AB - The Hyal-1 locus, which we have previously described and mapped to mouse chromosome 9, influences the serum levels and molecular weight forms of hyaluronidase. We have also shown that the growth of two transplantable tumors, the 3LL carcinoma and the B16F10 melanoma, is influenced by the alleles at Hyal 1, in that the tumors develop more slowly in congenic B6.C-Hyal-1a (also called HW23) mice than in the parental Hyal-1b C57BL/6 mice. Here we present evidence that tumor development is stimulated and mortality is accelerated in B6.C-Hyal-1a mice grafted with 3LL carcinoma cells when treated with alpha/beta interferon (IFN-alpha/beta) or with IFN-beta, whereas in IFN-treated C57BL/6 mice 3LL tumor growth is inhibited. Likewise, in B6.C-Hyal-1a mice grafted with B16F10 melanoma cells, IFN-alpha/beta treatment results in stimulation of tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth, whereas in IFN-treated C57BL/6 mice tumor growth is inhibited and mortality delayed. Thus, IFN-alpha/beta treatment of B6.C-Hyal-1a mice results in stimulation of tumor development and sometimes in accelerated mortality. This is the opposite of the usually described effect of IFN treatment in mice, which is inhibition of tumor development and delayed mortality, as was indeed observed in the C57BL/6 mice in the present experiments. These results provide the first indication that host genes can up- or down regulate the antitumor activity of IFN and that, on some genetic backgrounds, IFN treatment enhances rather than inhibits tumor development. This may help to explain the apparent discordance between mouse model studies, which hitherto have consistently reported inhibition of tumor formation by IFN, and the clinical trials, in which only a limited percentage of individuals show tumor regression while others have no beneficial effect or even have progression of disease in spite of the IFN treatment. PMID- 8516321 TI - Nucleic acid binding proteins in highly purified Creutzfeldt-Jakob disease preparations. AB - The nature of the infectious agent causing human Creutzfeldt-Jakob disease (CJD), a slowly progressive dementia, is controversial. As in scrapie, no agent-specific proteins or nucleic acids have been identified. However, biological features of exponential replication and agent strain variation, as well as physical size and density data, are most consistent with a viral structure--i.e., a nucleic acid protein complex. It is often assumed that nuclease treatment, which does not reduce infectious titer, leaves no nucleic acids of > 50 bp. However, nucleic acids of 500-6000 bp can be extracted from highly purified infectious complexes with a mass of approximately 1.5 x 10(7) daltons. It was therefore germane to search for nucleic acid binding proteins that might protect an agent genome. We here use Northwestern blotting to show that there are low levels of nonhistone nucleic acid binding proteins in highly purified infectious 120S gradient fractions. Several nucleic acid binding proteins were clearly host encoded, whereas others were apparent only in CJD, but not in parallel preparations from uninfected brain. Small amounts of residual host Gp34 (prion protein) did not bind any 32P-labeled nucleic acid probes. Most of the minor "CJD-specific" proteins had an acidic pI, a characteristic of many viral core proteins. Such proteins deserve further study, as they probably contribute to unique properties of resistance described for these agents. It remains to be seen if any of these proteins are agent encoded. PMID- 8516322 TI - Attentional control of early perceptual learning. AB - The performance of adult humans in simple visual tasks improves dramatically with practice. This improvement is highly specific to basic attributes of the trained stimulus, suggesting that the underlying changes occur at low-level processing stages in the brain, where different orientations and spatial frequencies are handled by separate channels. We asked whether these practice effects are determined solely by activity in stimulus-driven mechanisms or whether high-level attentional mechanisms, which are linked to the perceptual task, might control the learning process. We found that practicing one task did not improve performance in an alternative task, even though both tasks used exactly the same visual stimuli but depended on different stimulus attributes (either orientation of local elements or global shape). Moreover, even when the experiment was designed so that the same responses were associated with the same stimuli (although subjects were instructed to attend to the attribute underlying one task), learning did not transfer from one task to the other. These results suggest that specific high-level attentional mechanisms, controlling changes at early visual processing levels, are essential in perceptual learning. PMID- 8516323 TI - p53 mutations increase resistance to ionizing radiation. AB - Mouse and human tumors of diverse origin frequently have somatically acquired mutations or rearrangements of the p53 gene, or they have lost one or both copies of the gene. Although wild-type p53 protein is believed to function as a tumor suppressor gene, it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by gamma radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. We have used transgenic mice expressing one of two mutant alleles of p53 to test this prediction. Our results show that expression of both mutant variants of the mouse p53 gene significantly increases the cellular resistance of a variety of hematopoietic cell lineages to gamma radiation. These observations provide direct evidence that p53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests possible mechanisms through which alterations in the p53 gene might lead to oncogenic transformation. PMID- 8516324 TI - Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. AB - The 11;22 chromosomal translocation specifically linked to Ewing sarcoma and primitive neuroectodermal tumor results in a chimeric molecule fusing the amino terminal-encoding portion of the EWS gene to the carboxyl-terminal DNA-binding domain encoded by the FLI1 gene. We have isolated a fourth EWS-FLI1 fusion cDNA that is structurally distinct from the three forms previously described. To determine the transforming activity of this gene, alternative forms of the EWS FLI1 fusion were transduced into NIH 3T3 cells. Cells expressing either type 1 or type 4 fusion constructs formed foci in culture and colonies in soft agar, indicating that EWS-FLI1 is a transforming gene. EWS-FLI1 deletion mutants were created to map functionally the critical regions within the chimera. Deletion of either the EWS domain or the FLI1 corresponding to the DNA-binding domain totally abrogated the ability for EWS-FLI1 to transform 3T3 cells. These data indicate that the oncogenic effect of the 11;22 translocation is caused by the formation of a chimeric transcription factor. Formation of chimeric transcription factors has now been demonstrated to promote tumors of both neuroectodermal and hematopoietic origin, suggesting that this may be a common mechanism in human carcinogenesis. PMID- 8516325 TI - Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. AB - We have analyzed determinants of the synthesis and secretion of apolipoproteins including mRNA for apolipoproteins, in the human colon carcinoma cell line Caco-2 during differentiation in continuous culture. Significant increases in both cellular and secreted apolipoprotein A-I were observed early in the differentiation process. Increases in apolipoprotein B were limited to secreted protein and started later in the differentiation process. Levels of mRNA for apolipoproteins A-I, A-IV, B, C-III, and E increased significantly between the time cells reached confluence and 1 week postconfluence. The kinetics of mRNA accumulation were influenced by culture conditions. Nuclear extracts from postconfluent Caco-2 cells contained increased amounts of protein that bound to oligonucleotides containing the control regions of the apolipoprotein A-I and B genes. A competition experiment suggested that this protein recognized the control regions of both genes. We propose to name this protein DRIFT-1 (differentiation-related intestinal factor for transcription 1). PMID- 8516326 TI - Relaxation kinetics of the Na+/glucose cotransporter. AB - An important class of integral membrane proteins, cotransporters, couple solute transport to electrochemical potential gradients; e.g., the Na+/glucose cotransporter uses the Na+ electrochemical potential gradient to accumulate sugar in cells. So far, kinetic analysis of cotransporters has mostly been limited to steady-state parameters. In this study, we have examined pre-steady-state kinetics of Na+/glucose cotransport. The cloned human transporter (hSGLT1) was expressed in Xenopus oocytes, and voltage-clamp techniques were used to monitor current transients after step changes in membrane potential. Transients exhibited a voltage-dependent time constant (tau) ranging between 2 and 10 ms. The charge movement Q was fitted to a Boltzmann relation with maximal charge Qmax of approximately 20 nC, apparent valence z of 1, and potential V0.5 of -39 mV for 50% Qmax. Lowering external Na+ from 100 to 10 mM reduced Qmax 40%, shifted V0.5 from -39 to -70 mV, had no effect on z, and reduced the voltage dependence of tau. Qmax was independent of, but tau was dependent on, temperature (a 10 degrees C increase increased tau by a factor of approximately 2.5 at -50 mV). Addition of sugar or phlorizin reduced Qmax. Analyses of hSGLT1 pre-steady-state kinetics indicate that transfer upon a step of membrane potential in the absence of sugar is due to two steps in the reaction cycle: Na+ binding/dissociation (30%) and reorientation of the protein in the membrane field (70%). The rate-limiting step appears to be Na+ binding/dissociation. Qmax provides a measure of transporter density (approximately 10(4)/microns 2). Charge transfer measurements give insight into the partial reactions of the Na+/glucose cotransporter, and, combined with genetic engineering of the protein, provide a powerful tool for studying transport mechanisms. PMID- 8516327 TI - A tumor necrosis factor-responsive long-term-culture-initiating cell is associated with the stromal layer of mouse long-term bone marrow cultures. AB - Long-term bone marrow cultures provide a model for the study of hematopoiesis. Both an intact, adherent stromal layer and hematopoietic stem cells are necessary components in these cultures. Mycophenolic acid treatment of mouse long-term bone marrow cultures depletes them of all assayable hematopoietic precursors. The residual stromal cells are functional and support hematopoiesis if new progenitor cells are supplied. We now show that these mycophenolic acid-treated stromal cell cultures contain cells capable of hematopoietic differentiation without the addition of new progenitors. When treated with tumor necrosis factor alpha (20 200 units/ml), the apparently pure stromal cultures undergo an intense burst of hematopoietic activity. After 4 days such cultures contain approximately 2 x 10(6) hematopoietic cells and, by 1 week, they are indistinguishable from control long-term cultures that were not treated with mycophenolic acid. These results suggest that the stromal cultures either contain hematopoietic stem cells that are maintained quiescent and mycophenolic acid-resistant, perhaps by intimate contact with the stroma, or contain adherent cells that can be induced to differentiate into hematopoietic stem cells. These stem cells are primitive, in that they are capable of multilineage development in the long-term cultures, but are unable to form spleen colonies or myeloid colonies in semisolid medium. These data demonstrate that the adherent fraction of cultured bone marrow contains very primitive hematopoietic cells and that tumor necrosis factor alpha activates their proliferation and differentiation. They also suggest a strategy for obtaining the earliest progenitors free of other, more mature cell types. PMID- 8516328 TI - Nerve growth factor induces neuron-like differentiation of an insulin-secreting pancreatic beta cell line. AB - Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression of genes normally responsive to NGF in neurons, including the NGF-1A gene. Inasmuch as pancreatic beta cells arise from the embryonic endoderm, these results suggest that NGF may play a wider role during development than previously thought-a role not restricted to cells of neuroectodermal origin--and that endocrine and neuronal cells share a developmental pathway. The specific effect of NGF on an early pancreatic beta cell line also suggests that this neurotrophic factor might form the basis of a therapeutic treatment for some types of diabetes by inducing the proliferative differentiation of islet cells. PMID- 8516329 TI - Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. AB - Helicobacter pylori has been associated with gastritis, peptic ulcer, and gastric adenocarcinoma. We report the nucleotide sequence and expression of an immunodominant antigen of H. pylori and the immune response to the antigen during disease. The antigen, named CagA (cytotoxin-associated gene A), is a hydrophilic, surface-exposed protein of 128 kDa produced by most clinical isolates. The size of the cagA gene and its protein varies in different strains by a mechanism that involves duplication of regions within the gene. Clinical isolates that do not produce the antigen do not have the gene and are unable to produce an active vacuolating cytotoxin. An ELISA to detect the immune response against a recombinant fragment of this protein detects 75.3% of patients with gastroduodenal diseases and 100% of patients with duodenal ulcer (P < 0.0005), suggesting that only bacteria harboring this protein are associated with disease. PMID- 8516330 TI - A stationary-phase protein of Escherichia coli that affects the mode of association between the trp repressor protein and operator-bearing DNA. AB - Highly purified preparations of trp repressor (TrpR) protein derived from Escherichia coli strains that were engineered to overexpress this material were found to contain another protein, of 21 kDa. The second protein, designated WrbA [for tryptophan (W) repressor-binding protein] remained associated with its namesake through several sequential protein fractionation steps. The N-terminal amino acid sequence of the WrbA protein guided the design of two degenerate oligonucleotides that were used as probes in the cloning of the wrbA gene (198 codons). The WrbA protein, in purified form, was found by several criteria to enhance the formation and/or stability of noncovalent complexes between TrpR holorepressor and its primary operator targets. The formation of an operator holorepressor-WrbA ternary complex was demonstrated by gel mobility-shift analysis. The WrbA protein alone does not interact with the trp operator. During the stationary phase, cells deficient in the WrbA protein were less efficient than wild type in their ability to repress the trp promoter. It is proposed that the WrbA protein functions as an accessory element in blocking TrpR-specific transcriptional processes that might be physiologically disadvantageous in the stationary phase of the bacterial life cycle. PMID- 8516331 TI - Nonexponential protein relaxation: dynamics of conformational change in myoglobin. AB - The picosecond evolution of the tertiary conformation of myoglobin (Mb) after photodissociation of MbCO was investigated at room temperature by probing band III, a weak iron-porphyrin charge-transfer transition near 13,110 cm-1 (763 nm) that is sensitive to the out-of-plane displacement of the iron. Upon photolysis, the iron moves out of the plane of the porphyrin, causing a blue-shift of band III and a concomitant change in the protein conformation. The dynamics for this functionally important motion are highly nonexponential, in agreement with recent molecular dynamics simulations [Kuczera, K., Lambry, J.-C., Martin, J.-L. & Karplus, M. (1993) Proc. Natl. Acad. Sci. USA 90, 5805-5807]. The conformational change likely affects the height of the barrier to ligand rebinding and may explain nonexponential NO rebinding. PMID- 8516332 TI - Nonexponential relaxation after ligand dissociation from myoglobin: a molecular dynamics simulation. AB - Molecular dynamics simulations of myoglobin after ligand photodissociation show that the out-of-plane motion of the heme iron has a rapid subpicosecond phase followed by a slower nonexponential process involving more global protein relaxation. Individual trajectories show rather different behavior, suggesting there is an inhomogeneous component to the relaxation. The calculated time dependence of the iron motion over 100 ps is in excellent agreement with the frequency shift of band III of the heme group [see Lim, M., Jackson, T. A. & Anfinrud, P. A. (1993) Proc. Natl. Acad. Sci. USA 90, 5801-5804]. If that the barrier to rebinding depends on the out-of-plane iron position, the time dependence obtained from the simulation can explain the nonexponential room temperature geminate recombination of NO. PMID- 8516334 TI - Change in the signal-response sequence responsible for asymmetric isolation between Drosophila planitibia and Drosophila silvestris. AB - Drosophila planitibia and Drosophila silvestris form a species pair that is an example of species diverged through a founder event. These species exhibit asymmetric sexual isolation, courtships between D. planitibia males and D. silvestris females being more successful than courtships between D. silvestris males and D. planitibia females. When analyzing the signal-response courtship sequence in these species, we found that D. silvestris females responded to male circling by standing or preening while D. planitibia females required further signals from the male to stop walking. The main reason for the reduced mating success rate of D. silvestris males with D. planitibia females was that the females responded to male circling by walking and the males did not proceed to the head-under-wings (HUW) position of a walking female. Another critical phase in these courtships was the HUW position in D. silvestris, where males proceeded almost immediately to wing and leg vibration. The courtships between D. planitibia male and D. silvestris female proceeded in a signal-response coordination until the male went to the HUW position, where he fanned his wings for too long a period before proceeding to wing and leg vibration. Thus, it seems that the asymmetric isolation between D. planitibia (ancestral species) and D. silvestris (derived species) is mainly due to a loss of transitions in the signal response chain of D. silvestris. A change in the behavior of the males in the HUW position has caused further isolation between the species in both directions. PMID- 8516333 TI - Folding and intracellular transport of the yeast plasma-membrane H(+)-ATPase: effects of mutations in KAR2 and SEC65. AB - We have developed two independent assays to study the integration, folding, and intracellular transport of the polytopic plasma membrane H(+)-ATPase in yeast. To follow folding, controlled trypsinolysis was used to distinguish between the E1 conformation of the ATPase (favored in the presence of ADP) and the E2 conformation (favored in the presence of vanadate). By this criterion, wild-type ATPase appears to recognize its ligands and assume distinct conformations within a short time after its biosynthesis. To follow intracellular transport, we have exploited the fact that export of newly synthesized ATPase from the endoplasmic reticulum is accompanied by kinase-mediated phosphorylation, leading to a shift in electrophoretic mobility. Because proper folding is required for transport from the endoplasmic reticulum, the mobility shift also serves as a convenient bioassay for correct folding. As a first step toward identifying cell components important in folding of the nascent ATPase, we have used the dual assays to examine the role of KAR2, encoding the yeast homolog of immunoglobulin heavy chain binding protein/78-kDa glucose-regulated protein, and SEC65, encoding a subunit of the yeast signal recognition particle. Although mutation of KAR2 caused defective translocation of several secretory precursors into the endoplasmic reticulum lumen, ATPase folding and intracellular transport were unperturbed. By contrast, in a sec65 mutant, the folding and intracellular transport of newly synthesized ATPase were delayed. Our data suggest that conformational maturation of the ATPase is a rapid process in wild-type cells and that membrane integration mediated by signal recognition peptide is important for the proper folding of this polytopic protein. PMID- 8516335 TI - Long-term reversal of diabetes by the injection of immunoprotected islets. AB - The intraperitoneal injection of insulin-producing islets immunoprotected by an alginate-poly(amino acid) membrane is a potential method of reversing diabetes without the need for lifelong immunosuppression. Previous attempts to demonstrate this technology in large animals have failed, preventing application in humans. We have determined that key factors responsible for these past failures include cytokine (interleukins 1 and 6 and tumor necrosis factor) stimulation by mannuronic acid monomers from alginate capsules with weak mechanical integrity, which results in fibroblast proliferation. With this insight, we formulated mechanically stable microcapsules by using alginate high in guluronic acid content and report prolonged reversal of diabetes in the spontaneous diabetic dog model by the intraperitoneal injection of encapsulated canine islet allografts. Euglycemia, independent of any exogenous insulin requirement, was noted for up to 172 days. Graft survival, evidenced by positive C-peptide release, was noted for as long as 726 days in a recipient receiving a single injection of immunoprotected islets. Histological evidence of viable islets retrieved from the peritoneal cavity 6 months posttransplant confirmed the biocompatibility and immunoprotective nature of this capsule formulation. The finding that intraperitoneal injection of alginate-immunoprotected islets, a minimally invasive surgical procedure, is effective in prolonged (> 1 year) maintenance of glycemic control, without the need for lifelong immunosuppression, may have significant implications for the future therapy of type I diabetes in humans. PMID- 8516336 TI - Nuclear progesterone receptor is mainly heat shock protein 90-free in vivo. AB - Heat shock protein 90 (hsp90) is associated with many steroid receptors in tissue homogenates. It is widely accepted that hsp90 regulates the binding of the receptor to the corresponding gene regulatory element. However there is no unequivocal evidence that steroid receptor-hsp90 complexes are present in the intact cells. We demonstrate here the absence of progesterone receptor (PR)-hsp90 complexes in intact target cell nuclei, using immunohistochemical and biochemical methods to determine the location and composition of the nonliganded (aporeceptor) and liganded (holoreceptor) PR complexes. In the chicken oviduct cells, both apo- and holoreceptors were nuclear, while hsp90 was exclusively cytoplasmic. When expressed transiently in HeLa cells, hsp90 was detected in the cytoplasm and PR was detected in the nucleus. Their location or staining intensity was not affected when they were coexpressed in the same cells. To confirm that the sensitivity of the immunohistochemical detection of hsp90 and PR did not differ significantly, a chimeric hsp90-PR was transiently expressed in HeLa cells. Both hsp90 and PR antigens of the chimera were detected in nuclei with the same intensity. In homogenates of the same tissue samples that were used for immunohistochemistry, the PR was complexed with hsp90. Hsp90-PR complexes were formed in vitro when immature bursa of Fabricius, known to contain high levels of hsp90, was homogenized in the presence of hsp90-free aporeceptor, while holoreceptor did not associate with hsp90. Our data show that nuclear PR is not complexed with hsp90 in vivo and suggest that the 8S-PR may be an in vitro artifact generated during tissue processing. PMID- 8516337 TI - Polar/apolar compounds induce leukemia cell differentiation by modulating cell surface potential. AB - The mechanism of action of polar/apolar inducers of cell differentiation, such as dimethyl sulfoxide and hexamethylene-bisacetamide, is still obscure. In this paper evidence is provided that their effects on murine erythroleukemia cells are modulated by various extracellular cations as a precise function of the cation effects on membrane surface potential. The interfacial effects of the inducers were directly measured on the charged electrode, showing that both dimethyl sulfoxide and hexamethylene-bisacetamide, at the effective concentrations for cell differentiation and within the physiological range of charge density, adsorb at the charged surface and produce a potential shift. A linear correlation was found between this shift and the inducer effects on cell differentiation. Besides offering a different interpretation of the mechanism of action of the inducers, these findings indicate that surface potential has a signaling function. They may also be relevant to cancer treatments based on tumor-cell commitment to terminal differentiation. PMID- 8516338 TI - Spectroscopic evidence for a heme-heme binuclear center in the cytochrome bd ubiquinol oxidase from Escherichia coli. AB - The cytochrome bd complex is a ubiquinol oxidase, which is part of the aerobic respiratory chain of Escherichia coli. This enzyme is structurally unrelated to the heme-Cu oxidases such as cytochrome c oxidase. While the cytochrome bd complex contains no copper, it does have three heme prosthetic groups: heme b558, heme b595, and heme d (a chlorin). Heme b558 appears to be involved in the oxidation of quinol, and heme d is known to be the site where oxygen binds and is reduced to water. The role of heme b595, which is high spin, is not known. In this paper, CO is used to probe the oxygen-binding site by use of Fourier transform infrared spectroscopy to monitor the stretching frequency of CO bound to the enzyme. Photodissociation at low temperature (e.g., 20 K) of the CO-heme d adduct results in CO associated with the protein within the heme binding pocket. This photodissociated CO can subsequently relax to form a kinetically trapped CO heme b595 adduct. The data clearly show that heme d and heme b595 must reside within a common binding pocket in the enzyme. The catalytic active site where oxygen is reduced to water is, thus, properly considered to be a heme d-heme b595 binuclear center. This is analogous to the heme alpha 3-Cu(B) binuclear center in the heme-Cu oxidases. Heme b595 may play roles analogous to those proposed for the Cu(B) component of cytochrome c oxidase. PMID- 8516339 TI - Crypt/villus site of substrate-dependent regulation of mouse intestinal glucose transporters. AB - The intestinal epithelium is in a constant state of turnover, with cells differentiating at the crypts and then migrating toward the tips of the villi. Does substrate-dependent regulation of intestinal Na+/D-glucose cotransporters occur only in crypt cells, or can transport activity be subsequently reprogrammed in mature enterocytes? We used in situ, glucose-protectable specific phlorizin binding to determine site density of brush border glucose transporters in enterocytes fractionated along the crypt/villus axis of mice that were killed shortly after drastic changes in carbohydrate levels of their diets. Dietary carbohydrate-induced changes in site density of specific phlorizin binding initially appeared only in crypt cells before spreading, over the course of several days, to the villus tips. Thus, only crypt cells perceive the signal for glucose transporter regulation, and the observed time lag of diet-induced changes in intestinal glucose uptake is due mainly to cell migration times. PMID- 8516340 TI - A unified perspective on copper deficiency and cardiomyopathy. AB - Dietary copper restriction in rats results in cardiomyopathy. In rats fed copper restricted diets from weaning for 5 to 8 weeks, a concentric hypertrophy is apparent, whereas postweaning copper restriction does produce cardiomyopathy without apparent hypertrophy. Both sets of circumstances appear to affect the integrity of the basal laminae of cardiac myocytes and capillaries. In rats fed copper-restricted diets from weaning, decreases in cytochrome c oxidase are related not only to copper's role as a coenzyme, but also to a marked decrease in the nuclear encoded subunits of the enzyme complex. Decreased levels of the delta subunit of ATP synthase have been observed. However, such aberrations in mitochondrial enzymes, as well as morphologic alterations, apparently do not affect cardiac levels of ATP. This review suggests mechanisms of cardiac adaptation and initiation factors leading to cardiac hypertrophy. We present a hypothetical working model explaining the events leading to cardiac failure in the copper-deficient rat heart based on the present body of knowledge, and compare the pathology with other models of cardiomyopathies. PMID- 8516341 TI - Superoxide dismutase and pulmonary oxygen toxicity. AB - Three forms of superoxide dismutase (SOD) exist in the lung: CuZnSOD, MnSOD and extracellular SOD. Evidence suggests that both CuZnSOD and MnSOD are important in pulmonary defense against oxygen toxicity. Enhancement of pulmonary levels of CuZnSOD by transgenic overexpression of CuZnSOD, or tracheal insufflation of liposome-encapsulated or polyethylene glycol-conjugated CuZnSOD, protects animals against oxygen toxicity. Likewise, transgenic overexpression of MnSOD, or induction of endogenous MnSOD by endotoxin, tumor necrosis factor, or interleukin 1, also protects animals against oxygen toxicity. The role of extracellular SOD in the pulmonary defense against oxygen toxicity is not clear. PMID- 8516342 TI - Differential sensitivity of rat uterine growth and epithelium hypertrophy to estrogens and antiestrogens. AB - Triphenylethylene antiestrogens are considered weak estrogen agonists based on their limited ability to induce estrogen responses, in particular uterine growth. We compared the uterotrophic activity of naturally occurring and synthetic estrogens with that of antiestrogens by quantitating uterine wet weight and hypertrophy in the uterine luminal and glandular epithelium. Immature rats received five daily injections of either an estrogen (17 beta-estradiol [E2], diethylstilbestrol [DES], or ethynyl estradiol [EE]) or an antiestrogen (tamoxifen [TAM], monohydroxytamoxifen [OH-TAM], or clomiphene citrate [CC]) (0.001-100 micrograms/rat/day) subcutaneously in sesame oil and were sacrificed approximately 2 hr after the last injection. Both DES and EE increased uterine weight at doses between 0.01-100 micrograms/rat/day; E2 was about 10-fold less potent. The antiestrogens increased uterine weight only slightly. DES, EE, and the three antiestrogens each increased luminal epithelium hypertrophy to over 3 fold above that in controls. While the potencies of these synthetic compounds differed (DES = EE > OH-TAM > TAM = CC), each hypertrophic response occurred over two log doses, and the response curves displayed identical slopes. E2, however, required a range of four log doses to achieve the same degree of luminal epithelium hypertrophy. The three antiestrogens elicited glandular epithelium hypertrophy up to 2-fold above controls at the same doses that induced luminal epithelium hypertrophy; the order of potency was OH-TAM > TAM = CC. However, the three estrogens increased glandular epithelium hypertrophy only marginally. Thus, under dosing conditions commonly used to assess uterotrophic activity, these "antiestrogens" are complete, albeit less potent, estrogen agonists in the luminal epithelium and, unlike estrogens, induce hypertrophy in the glandular epithelium. PMID- 8516343 TI - A growth hormone (GH) analog that antagonizes the lipolytic effect but retains full insulin-like (antilipolytic) activity of GH. AB - An analog of bovine growth hormone (bGH-M8: [Leu117, Arg119, Asp122]-bGH) with an idealized amphiphilic third alpha-helix has been proposed to be a functional antagonist of GH. In accordance with this proposition, bGH-M8 profoundly inhibited bGH-stimulated lipolysis by chicken adipose tissue in vitro. bGH-M8 alone was a weak agonist in the lipolytic assay (1.9% the potency of bGH). The present evidence indicates that bGH-M8 is a competitive antagonist of the lipolytic action of GH based upon the following results: (i) increasing concentrations of bGH-M8 (antagonist) produce progressively greater inhibition of GH-stimulated lipolysis; (ii) increasing concentrations of bGH (agonist) are capable of overcoming this antagonism; and (iii) Schild plot analysis (slope = 0.94) suggests a receptor antagonist with an equilibrium dissociation constant (KB) of 4.54 nM. In contrast to the antagonistic effects of bGH-M8 on bGH stimulated lipolysis, bGH-M8 retained full insulin-like ("antilipolytic") activity (i.e., inhibition of glucagon-induced lipolysis). bGH-M8 and bGH were similarly potent in eliciting antilipolytic effects in vitro. Moreover, the antilipolytic effects of bGH-M8 and bGH were additive. Therefore, the third alpha helix (particularly residues 117, 119, and 122) of bGH contains major structural determinants for the lipolytic effects of GH. The ability of bGH-M8 to act as an antagonist for at least one action of GH (lipolysis) while being a full agonist for another (antilipolysis) suggests that different domains of GH are responsible for its various biologic activities, possibly involving different binding sites and/or signal transduction mechanisms. PMID- 8516344 TI - Synthesis of 18-hydroxycortisol and 18-oxocortisol in bovine adrenal zona glomerulosa mitochondria. AB - The biosynthesis of 18-hydroxycortisol and 18-oxocortisol from cortisol was studied in calf adrenal zona glomerulosa mitochondria. Cortisol is converted to 18-hydroxycortisol and 18-oxocortisol in the same mitochondrial preparation in which corticosterone is metabolized to 18-hydroxycorticosterone and aldosterone. Cortisol and 18-hydroxycortisol interacted with mitochondria to cause a Type I differential spectrum, which was decreased by sodium dithionite. The metabolism of cortisol to 18-hydroxycortisol and 18-oxocortisol was inhibited by metyrapone in a competitive way. Cortisol was a competitive inhibitor of the transformation of corticosterone into 18-hydroxycorticosterone and aldosterone, and corticosterone was a competitive inhibitor of the transformation of cortisol into 18-hydroxycortisol and 18-oxocortisol, with a Ki very similar to the Km for the transformation of that steroid to aldosterone. These results indicate that cortisol is metabolized to 18-hydroxycortisol and 18-oxocortisol by a mitochondrial cytochrome P-450, which is the same as that which catalyzes the conversion of corticosterone into aldosterone. PMID- 8516345 TI - Differential effects of ethanol on permissive versus nonpermissive macrophages infected with Legionella pneumophila. AB - The effect of ethanol treatment was studied in terms of effect on permissive versus nonpermissive macrophages for growth of Legionella pneumophila, which is an intracellular bacterium causing pneumonia in immunocompromised patients. It was found that ethanol treatment of permissive macrophages from L. pneumophila susceptible A/J mice evinced a decrease in replication of the bacteria compared with nontreated infected macrophages. Whereas there was more than a 100-fold increase in Legionella growth over a 48-hr culture period in infected A/J mouse macrophages, treatment of the macrophages with 0.5% ethanol depressed the ability of the macrophages to be infected by Legionella approximately 45%. A lower concentration of ethanol had a lesser effect but still resulted in inhibition of the ability of the cells to replicate Legionella. In contrast to ethanol-induced inhibition of the A/J mouse macrophages to replicate Legionella, macrophages from Legionella-resistant BALB/c mice, which only minimally replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr period), treatment with ethanol resulted in their greater replication of the Legionella. This effect was most marked with the 1.0% concentration of ethanol after 7 days of pretreatment, while the 0.5% and 0.1% concentrations of alcohol caused less enhancement of bacterial growth in the cells, but these concentrations still had a significant enhancement effect. Thus, ethanol had differing effects on growth of the opportunistic intracellular bacterium Legionella in macrophages from permissive versus nonpermissive mice. Studies on the mechanisms involved are in progress. PMID- 8516346 TI - Reduced renal accumulation and toxicity of cisplatin in experimental galactosemia. AB - The kidneys of streptozotocin (STZ)-diabetic rats are resistant to certain toxic effects of the antineoplastic drug cisplatin. The mechanism is unknown. This study used the galactosemic rat model to test the hypothesis that the apparent diabetes-induced protection is due to changes in the kidney secondary to chronically elevated hexose concentrations. Galactosemic rats are normoinsulinemic and are free from many of the multiple biochemical abnormalities seen in STZ diabetics. The experiments compared renal cortical platinum (Pt) and blood urea nitrogen (BUN) levels after intraperitoneal injection of 5 mg/kg of cisplatin in galactosemic, STZ-diabetic, and age-matched nondiabetic Sprague Dawley rats. Nephrotoxicity was defined as a BUN concentration ratio (after to before cisplatin) > 2.5. The results demonstrate that the kidneys of both galactosemic and STZ-diabetic rats became resistant to cisplatin-induced elevation of BUN and, further, that the development of the protection was related to the duration of the diabetic state. Although the protective effect developed more slowly in the galactosemic rats, the attenuation of the rise in BUN was ultimately comparable to that seen in STZ diabetics. Renal cortex [Pt] after cisplatin injection was significantly lower in galactosemics and STZ diabetics compared with age-matched nondiabetics, with the order nondiabetics > galactosemics > STZ diabetics. It was noted, however, that renal Pt accumulation was maximally depressed within 4 weeks of experimental diabetes, whereas the BUN ratio continued to decline with increasing duration of both galactosemia and STZ diabetes. Thus, reduced renal Pt accumulation cannot by itself explain the progressive attenuation of the toxicity. The results support the hypothesis and suggest that the galactosemic rat will be a useful model for mechanistic study of diabetes-induced protection from cisplatin nephrotoxicity. PMID- 8516347 TI - Topically active ocular carbonic anhydrase inhibitors: novel biscarbonylamidothiadiazole sulfonamides as ocular hypotensive agents. AB - A novel homologous series of bis(carbonyl)amidothiadiazole sulfonamides has been synthesized for structure-activity relationship studies, and initial characterization has been performed. The goal was synthesis of thiadiazole derivatives with appropriate lipid and water solubilities for utility as topically (corneal application) active carbonic anhydrase (CA) inhibitors. This series has solubility properties and pKa which bracket those of acetazolamide- the prototypical CA inhibitor. All of these compounds are active as in vitro CA inhibitors, and are 10-25% as potent as acetazolamide as in vitro enzyme inhibitors. Two of these compounds act as ocular hypotensive agents after topical application of a single dose to the corneas of normotensive New Zealand albino rabbits. The efficacy of the lead compound of this series (in this one model) is approximately equivalent to that of topical CA inhibitors that are presently in clinical trial. None of these novel compounds reacts to an appreciable extent with free sulfhydryl groups (a predictor of toxicity). This family of compounds will be useful for future studies of ocular pharmacokinetics, as well as ocular and systemic effects of topical administration of CA inhibitors. These and future studies may lead to development of thiadiazole sulfonamides useful in the management of glaucoma. PMID- 8516348 TI - Decreased plasma proteins, increased total plasma-free amino acids, and disturbed amino acid metabolism in the hereditary severe anemia of the Belgrade laboratory (b/b) rat. AB - The plasma amino acid pattern has been investigated in severely anemic Belgrade laboratory (b/b) rats. Nonanemic heterozygous (b/+) or normal homozygous (+/+) rats of the same age (six weeks) were used as controls. Decreased plasma proteins, increased total free amino acid, and urea concentrations in plasma associated with increased urea and 3-methylhistidine urinary excretion were found, indicating protein and amino acid metabolic alterations in anemic b/b rats. Plasma alanine, glutamine, tyrosine, and phenylalanine concentrations were increased. The significantly reduced molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine suggested severe disturbance in the hepatic energy-producing system and derangement of hepatic energy status. Partial or complete reversal of the anemia within 3 days by red blood cell transfusion or within 3 weeks by iron treatment resulted in normalization of tyrosine, alanine, glutamine, and total amino acid concentrations in plasma, as well as of molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine. This indicated a better oxygen supply to the liver and normalization of the hepatic energy status. These findings suggest that the metabolic disturbances in the b/b rat are the consequence of hypoxia due to the severe anemia. PMID- 8516349 TI - Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. AB - Vinblastine has been demonstrated to inhibit nicotinic acetylcholine receptor (nAChR) activity in adrenal chromaffin cells and superior cervical ganglia and to alter agonist binding affinity to nAChR of the electric organ of Torpedo californica. In cultured chromaffin cells, vinblastine (IC50, 8.9 microM) is significantly more potent than hexamethonium (IC50, 16 microM) and decamethonium (IC50, 18 microM) and significantly less potent than d-tubocurarine (IC50, 2 microM), pentolinium (IC50, 0.6 microM), and mecamylamine (IC50, 0.1 microM) in inhibiting nAChR-stimulated catecholamine release. These results demonstrate that vinblastine has moderately potent anti-nAChR activity on adrenal nAChR. On the other hand, vinblastine does not interfere with phrenic nerve stimulation of rat diaphragm musculature in concentrations up to 200 microM. However, in relatively high doses, vinblastine (10-200 microM) produces an increase in baseline tension of diaphragm muscle. This effect is concentration related (EC50, approximately 88 microM), reversible, and independent of phrenic nerve stimulation. The elevation in baseline tension is unaffected by nAChR blockade via d-tubocurarine, but is dependent upon the presence of extracellular calcium. The results suggest that vinblastine's antinicotinic actions are selective for neuronal-type nAChR and do not extend to nAChR of mammalian skeletal muscle. High concentrations of vinblastine appear to elicit contractures of skeletal muscle that are unrelated to nAChR. PMID- 8516350 TI - Longitudinal changes during the development of hypertension in rats fed excess chloride and sodium. AB - The effects of supplemental NaCl, KCl, and Na acetate on the blood pressure of weanling rats fed semipurified diets and diets based on naturally high salt products, like cottage cheese, were examined in two studies. Within 2 weeks of initiation of dietary treatments, rats fed supplemental chloride had elevated blood pressure and lowered plasma renin activity, which persisted throughout the 8-week study. The effect of supplemental sodium on blood pressure was not significant until after 6 weeks of dietary treatment. The initial increase in blood pressure preceded the slowed growth observed in rats fed excess chloride or sodium. Urinary volume and urinary excretion of calcium, magnesium, phosphorus, sodium, and chloride were increased when supplemental chloride or sodium was fed, but tissue electrolyte and plasma atrial natriuretic peptide concentrations remained constant. Two changes preceded the rise in blood pressure: rats fed supplemental chloride had enlarged kidneys, and those fed supplemental sodium had elevated hematocrits, suggesting a transient shift among fluid compartments, after only 6 days of treatment. These data suggest that the hypertension induced by ingestion of supplemental (14.6 mg CI/g of diet) chloride is mediated by changes in renal function. Ingestion of excess sodium depressed bone magnesium concentrations in Study 1 and after 24 days in Study 2; the impact of this "relative" magnesium depletion on blood pressure deserves further study. PMID- 8516351 TI - Acute effects of pentobarbital in a monkey operant behavioral test battery. AB - The effects of acute pentobarbital treatment were assessed using a complex operant test battery containing five tasks in which correct performance is thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult, male rhesus monkeys were tested 15 min after IV injection of saline or pentobarbital (1, 3, 5.6, 10, or 15 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by PBT was TRD > IRA = DMTS = PR > CPR, in which sensitivity was defined as a significant disruption in any aspect of task performance. PBT slowed response rates at 10.0 and/or 15.0 mg/kg in all tasks. Accuracy was decreased in the TRD task at > or = 5.6 mg/kg but doses of > or = 10.0 mg/kg were required to decrease accuracy in the IRA, DMTS, and CPR tasks. Thus, behavior thought to model time perception (TRD) was more sensitive than behavior modeling learning (IRA), short-term memory and attention (DMTS), and motivation (PR). CPR was the least sensitive behavior. Because pentobarbital exerts its effects at least in part via GABA systems, the effects in the current study were compared with those of a previous study of the acute effects of diazepam. The two compounds exerted fundamentally different effects on operant test battery performance. PMID- 8516352 TI - Anorectic specificity as measured in a choice paradigm in rhesus monkeys. AB - The present report describes a new procedure for assessing anorectic specificity. Two rhesus monkeys (Macaca mulatta) surgically prepared with indwelling intragastric catheters were trained in a discrete trial choice paradigm to respond for either food or visual access to a room containing other monkeys. Our hypothesis was that a specific anorectic would reduce only food-maintained responding; responding to open a window would either not be affected or would increase. Caloric preloads, d-amphetamine, (d,l)-fenfluramine, and cholecystokinin octapeptide all decreased food-maintained responding and had no effect on or increased responding maintained by window opening. These results demonstrate that choice procedures are useful for assessing anorectic specificity. PMID- 8516353 TI - Regional analysis of 5-HT1A receptors in two species of Peromyscus. AB - Two species of deer-mice, Peromyscus maniculatus (P. man) and Peromyscus leucopus (P. leu), were compared for differences in 5-hydroxytryptamine1A (5-HT1A) receptor number and affinity. Both species enter into torpor; however, P. man enters spontaneous torpor with a higher frequency and for a longer duration than P. leu. Further, compared to P. leu a higher percentage of P. man exhibit daily torpor. Deer mice can be induced to enter torpor by a reduction in food supply, shortened photoperiods, and decreasing ambient temperature. Under these conditions, P. man enters into torpor more frequently, for longer durations, and with a higher percentage of individuals as compared to P. leu. [3H]8-OH-DPAT was used to label 5-HT1A brain receptors in three brain regions: the frontal cortex, brainstem, and striatum. In addition, the hypothalamus and hippocampus were examined for 5-HT1A receptor differences; however, no measurable specific binding could be determined in these regions. In the frontal cortex, the Bmax values were significantly lower in P. man compared to P. leu. There were no significant differences in the Bmax values in the striatum and brainstem between P. man and P. leu. Further, there were no significant differences in the Kd values between the two species in any of the brain regions examined. The absence of any difference in receptor number or affinity in any of the brain regions examined, except the cortex, suggests that the 5-HT1A receptor is most likely not involved in a more efficient pathway to torpor. PMID- 8516354 TI - Opioid and nonopioid interactions in two forms of stress-induced analgesia. AB - Stressful environmental events activate endogenous mechanisms of pain inhibition. Under some circumstances the analgesia is blocked by naloxone/naltrexone ("opioid"), while under others it is not ("nonopioid"). The existence of these two categories of analgesia leads to the question of how they are related. In a collateral inhibition model proposed by Kirshgessner, Bodnar, and Pasternak (1982), opiate and nonopiate mechanisms were viewed as acting in a mutually inhibitory fashion. In the present experiments, rats were exposed to either of two environmental stressors that produce a nonopioid stress-induced analgesia (SIA) following injections of the opiate antagonist naltrexone or agonist morphine. In the presence of naltrexone, SIA produced by either cold water swim (CWS) or social defeat was enhanced. These same SIAs were found to attenuate the analgesic effect of morphine, demonstrating that an activation of opioid systems can inhibit nonopioid analgesias. These results support an inhibitory interaction of opioid and nonopioid mechanisms in some forms of stress-induced analgesia. PMID- 8516355 TI - Changes in the incidence and duration of electroconvulsions after acute or subchronic treatment with methamphetamine in mice. AB - The effects of acute or subchronic treatment with methamphetamine on the incidence, intensity, and duration of electroconvulsion were investigated in mice. The convulsion was induced by electrical stimulation (100 Hz, 60 mA, 0.1-s duration) through electrodes located at each ear of mice, then analyzed by the vibration monitoring apparatus. Acute methamphetamine (3 mg/kg) reduced the incidence of the electroconvulsion in mice; however, the duration of each phase of the convulsion was prolonged by acute methamphetamine. Repeated administration of methamphetamine prolonged the duration of clonic phase of the convulsion and enhanced the acute methamphetamine-induced reduction in the incidence of electroconvulsion. These data indicate that the incidence of electroconvulsion is regulated by different mechanisms underlying the duration and intensity of the convulsion. PMID- 8516356 TI - Buspirone fails to affect the discriminative stimulus effects of cocaine. AB - Rats were trained to discriminate 4.0 mg/kg cocaine from saline in a two-lever, food-reinforced drug discrimination paradigm. Cocaine (0.5-8.0 mg/kg, IP) produced a dose-related increase in cocaine-appropriate responding, with the training dose of 4.0 mg/kg being the lowest dose that met criterion (> 90% cocaine-appropriate responding over the entire session) for substitution. Pretreatment with buspirone (2.0-16 mg/kg, IP) did not attenuate the discriminative stimulus properties of 4.0 mg/kg cocaine at doses up to those that caused complete suppression of responding (16 mg/kg, IP). In contrast, combinations of 0.12 mg/kg haloperidol with 4.0 mg/kg cocaine decreased cocaine appropriate responding from 100 to 65% while suppressing response rate to 50% of the response rate seen with the 4.0-mg/kg dose of cocaine alone. Thus, behaviorally active doses of buspirone failed to attenuate the discriminative stimulus effects of cocaine in a sensitive behavioral paradigm. PMID- 8516357 TI - Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection. AB - Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle. PMID- 8516358 TI - D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity. AB - The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominantly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes. PMID- 8516359 TI - Juvenile desipramine reduces adult sensitivity to imipramine in two behavioral tests. AB - The behavioral effects of adult imipramine administration were examined in female rats treated with desipramine as juveniles (JDES), treated with saline as juveniles (JSAL), and untreated as juveniles (JUNT). In the forced swimming test, the juvenile groups displayed similar behavioral effects of imipramine when administered short term following a pretest forced swimming exposure. Similar effects of imipramine were observed when administered long term prior to the only test exposure. When rats were not given a pretest forced swimming test exposure, short-term imipramine had no effect on JDES rats but did influence JSAL and JUNT rats. In the open-field test, short- and long-term imipramine treatment affected the behavior of JUNT and JSAL rats. Short-term imipramine treatment influenced open-field behavior of JDES animals, but long-term imipramine treatment had no effect. These results suggest that JDES treatment may permanently alter the neural mechanism underlying the behavioral effects of antidepressant treatment. PMID- 8516360 TI - Mitochondrial aldehyde dehydrogenase (ALDH2) polymorphism in AA and ANA rats: lack of genotype and phenotype line differences. AB - Polymorphism of the gene coding for mitochondrial ALDH2 in humans is known to be associated with differences in alcohol drinking behavior. Recently, two different alleles of the ALDH2 gene, ALDH2R and ALDH2Q, have been found in rats also and a possible relationship between the frequencies of the two alleles and drinking behavior has been proposed. In this study, we examined whether this polymorphism of ALDH2 was the underlying cause for the previously reported acetaldehyde accumulation in the alcohol-avoiding ANA rat line and, thus, could be one of the factors explaining the differences in alcohol drinking behavior between the ANA and the alcohol-preferring AA rat lines. The experimental animals were genotyped and their mitochondrial ALDH activities and blood acetaldehyde concentrations after ethanol injection were measured. The two lines did not differ in their frequencies of ALDH2R and ALDH2Q alleles. Thus, the polymorphism in the ALDH2 gene does not explain the acetaldehyde accumulation in ANA rats and it does not seem to be associated with differences in the alcohol drinking behavior in these rat lines. PMID- 8516361 TI - Discriminative stimulus properties of m-chlorophenylpiperazine. AB - Stimulus control was established in a group of 10 rats using a dose of m chlorophenylpiperazine (MCPP) of 0.8 mg/kg, administered IP, 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 27 sessions was required to reach criterion performance. Response rates were significantly suppressed by the training dose of MCPP (14 responses/min) as compared with saline sessions (38 responses/min). Subsequent to the establishment of stimulus control, tests of generalization were conducted with m-trifluoromethylphenylpiperazine (TFMPP), 6 chloro-2-(1-piperazinyl)-pyrazine (MK-212), and 5-methoxy-3-(1,2,3,6-tetrahydro-4 pyridinyl)-1H-indole (RU-24969). MCPP generalized completely to MK-212 and TFMPP at doses of the latter drugs of 0.7 and 1.0 mg/kg, respectively. Maximum generalization to RU-24969 was 67% at a dose of 1.0 mg/kg but only 4 of 10 subjects completed the test session. The present results indicate that MCPP is efficacious as a discriminative stimulus. In addition, because of MCPP's relative selectivity for the 5-hydroxytryptamine c(5-HT1C) receptor subjects trained with MCPP may prove valuable in assessing the respective functional contributions of 5 HT1C sites to the actions of a variety of serotonergic agents. PMID- 8516362 TI - Effect of anisomycin on the development of rapid tolerance to ethanol-induced motor impairment. AB - Male Wistar rats given a single moderate dose (1.7 g/kg, IP) of ethanol (EtOH), followed by six trials on the moving belt apparatus during the next hour, showed functional tolerance to the motor-impairing effects of a second dose given 24 h later if the first EtOH was preceded and followed by an injection of saline. The same EtOH dose and intoxicated practice did not produce tolerance if the saline injections were replaced by two doses of anisomycin (60 mg/kg each, SC) 15 min before and 105 min after the first dose of EtOH. This finding suggests that rapid tolerance, like chronic tolerance, requires de novo synthesis of protein during a short period immediately related to the test experience. PMID- 8516363 TI - Cocaine-stimulus generalization to two new designer drugs: methcathinone and 4 methylaminorex. AB - Rats were trained to discriminate 8 mg/kg cocaine from saline vehicle for the purpose of examining the stimulus properties of two novel and structurally related drugs of abuse recently confiscated on the illicit market: (+/ )methcathinone and cis(+/-)4-methylaminorex. The stimulus properties of these controlled substance analogs were compared with those of their parent compounds (+/-)cathinone and aminorex, respectively. All agents resulted in cocaine stimulus generalization with the following rank order of potency: aminorex (ED50 value = 0.8 microM/kg) > methcathinone (1.9 microM/kg) > cathinone (3.7 microM/kg) > 4-methylaminorex (5.2 microM/kg) > cocaine (7.6 microM/kg). PMID- 8516364 TI - Failure of the 5-HT2 receptor antagonist, ritanserin, to alter preference for alcohol in drinking rats. AB - The purpose of this study was to determine whether the 5-HT2 receptor antagonist, ritanserin, possesses the same sort of efficacy as another central 5-HT2 antagonist, amperozide, in reducing the pharmacologically induced preference for ethyl alcohol in the rat. Following the repeated administration of the inhibitor of aldehyde dehydrogenase, cyanamide, the preference for alcohol vs. water was determined in each of 20 Sprague-Dawley rats by a standard test using 3-30% concentrations. Then, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 9-15% and was consumed at a mean of 5.02 +/- 0.44 g/kg per day. After a 4-day predrug control test, either the saline control solution or 0.1, 0.3, or 1.0 mg/kg ritanserin was administered SC at 1600 h over 3 days. The daily intakes of alcohol of rats both during and after treatment with ritanserin were unchanged in terms of absolute g/kg and proportion of alcohol to total fluid consumed. Similarly, the control saline also was without any effect on alcohol consumption. Neither the consumption of food and total fluids nor the level of body weight was affected by these doses of ritanserin. Because our findings fail to coincide with previous reports on the effect of ritanserin on alcohol preference, it is envisaged that a methodological difference in earlier experimental procedures, such as the use of a weak 3% concentration of alcohol, could explain the discrepancy. Further, the present results contrast with the prolonged reduction in drinking produced by another 5 HT2 receptor antagonist, amperozide, which also acts centrally on dopaminergic neurons in the limbic system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516365 TI - D1 dopamine receptors in the nucleus accumbens modulate cocaine self administration in the rat. AB - Previous work using systemic injections of dopamine receptor antagonists has established that dopamine D1 receptors may have a role in cocaine self administration. The purpose of the present study was to test the hypothesis that these effects were mediated by dopamine D1 receptors in the region of the nucleus accumbens. Animals were trained to perform operant responses to self-administer cocaine via an IV catheter on a fixed-ratio 5 (FR 5) schedule of reinforcement. SCH23390, a selective D1 dopamine antagonist, significantly increased the self administration of cocaine when injected into the nucleus accumbens. This increase in self-administration is thought to reflect decreases in the magnitude of the reinforcer, similar to the increase observed when the dose of cocaine is reduced. Similar doses of SCH23390 injected into the posterior caudate nucleus failed to alter cocaine self-administration. These data suggest that D1 receptors in the nucleus accumbens are important for the reinforcing properties of cocaine. PMID- 8516366 TI - SCH23390, but not raclopride, decreases intake of intraorally infused 10% sucrose in adult rats. AB - When 10% sucrose is infused intraorally on postnatal days (PN) 7, 14, and 21, raclopride, a D2 dopaminergic antagonist, does not affect intake at any age and SCH23390, a D1 antagonist, does not affect intake on PN 7 but a large dose decreases intake on PN 14 and 21. To determine if this differential effect of the antagonists on PN 14 and 21 remains after further postnatal development, we studied adult rats in this intraoral intake test. Female (n = 77) and male (n = 81) adult rats, approximately 43 or 96 days old, were deprived for 4 h before intraoral infusion of 10% sucrose. Each rat was tested once and this was its first experience with sucrose. SCH23390 (133 or 267 micrograms/kg), raclopride (357 or 714 micrograms/kg), or saline vehicle was given IP at -15 min. The larger dose of SCH23390 significantly decreased intake of rats that were approximately 43 and 96 days old, but neither dose of raclopride changed intake at either age. These results suggest that D1, but not D2, receptors are necessary components of the central neural network that processes the unconditioned gustatory stimulus of 10% sucrose into mouthing and swallowing movements that maintain ingestion in late preweanling and adult rats under these conditions. PMID- 8516367 TI - Chronic treatment with valproate decreases the hypothermic response to clonidine. AB - Treatment with lithium (the prototype of an antimanic agent) attenuates responsiveness to the alpha 2-agonist clonidine in animal models. Valproate is now used to treat mania. The effect of treatment with this drug on responses mediated by an alpha 2-agonist have yet to be reported. The authors assessed the effect of a 14-day course of orally administered valproate on the rat's hypothermic response to clonidine. Treatment with valproate decreased this response. PMID- 8516368 TI - Diet and estrous cycle influence pain sensitivity in rats. AB - Effects of estrous cycle and acute and chronic access to palatable fluids on tail flick latency and opiate-induced analgesia were assessed in 124 female Long Evans rats. Following three consistent cycles, rats were water deprived for 8 h and then given ad lib access to 20 ml of either water, a 32% sucrose solution, or corn oil for 5 h. Nociceptive testing was conducted immediately preceding and 30, 60, and 90 min following an SC injection of morphine sulfate (7.5 mg/kg). Diestrus rats had prolonged premorphine tail-flick latencies compared to rats in proestrus. Rats that consumed corn oil had longer tail-flick latencies preceding and 30 min following morphine injections than rats that drank water or the sucrose solution. Rats were retested after they had ad lib access to the same fluid for 3 weeks. No estrous cycle differences were noted following chronic consumption. Rats with chronic access to sucrose showed increased baseline pain sensitivity and increased morphine-induced analgesia at 30, 60, and 90 min postinjection. These data support the notion that palatable fluid consumption attenuates estrous cycle-dependent differences in pain sensitivity. PMID- 8516369 TI - Effects of imipramine on circadian rhythms in the golden hamster. AB - The effects of the antidepressant imipramine on circadian organization were studied in wild-type and tau-mutant golden hamsters. Chronic imipramine treatment in doses ranging from 0-50 mg kg-1.day-1 depressed general activity and body temperature and caused a reduction in body weight but had no significant effect on circadian organization. Imipramine treatment did not affect the rate of reentrainment after a 6-h advance in the light-dark cycle, did not alter the advanced-phase angle of entrainment of tau-mutant hamsters, did not affect the free-running period of wild type hamsters, and did not alter the phase-response curve to light pulses. Because imipramine, a clinically effective antidepressant, did not have any measurable effect on the circadian system in these experiments, our results do not provide support for the hypothesis that the antidepressant action of imipramine is mediated by alterations in the circadian system. PMID- 8516370 TI - Angiotensin and captopril increase alcohol intake. AB - Reportedly both angiotensin II (ANG II) and angiotensin-converting enzyme (ACE) inhibitors reduce ethanol intake when they are injected SC into certain chronic experimental conditions in the rat. The ACE inhibitors are suggested to reduce ethanol intake by increasing ANG II synthesis in the brain. The present results show that several different methods can produce opposite effects of ANG II and the ACE inhibitor captopril on ethanol intake. Continuous intraventricular infusions of ANG II for 7 days or low doses of oral or SC-infused captopril for up to 12 days increased the intake of ethanol. The only reduction of ethanol intake resulted from a universal blockade of all ACE in both the brain and periphery, a condition in which ANG II could not possibly mediate the decrease. The results contradict the hypothesis that ethanol intake is suppressed by centrally acting or centrally synthesized ANG II. ACE inhibitors may reduce ethanol intake only when they affect the brain as well as the periphery. PMID- 8516371 TI - Enhancement of amphetamine anorexia after chronic administration of sulpiride in rats. AB - Long-term administration of sulpiride induces hyperphagia and obesity in female rats. After sulpiride withdrawal, a significant hypophagia has been observed. The hyperphagia could be related to the blockade and the hypophagia to supersensitivity of dopamine D2 receptors, in particular those D2 receptors located in the perifornical hypothalamus. If this were the case, an enhancement of anorexia induced by amphetamine and dopamine should be observed after interruption of long-term sulpiride treatment. Two doses of systemic sulpiride (20 or 200 mg/kg) and one dose of intrahypothalamic sulpiride (15 micrograms) were tested. Amphetamine was administered by systemic or intrahypothalamic infusion. Dopamine was administered in the hypothalamus. After withdrawal of systemic administration of sulpiride (200 mg/kg), an enhancement of anorexia induced by systemic amphetamine was observed. However, the anorexia induced by intrahypothalamic injections of amphetamine or dopamine was not affected by the interruption of the sulpiride treatment. These results suggest that the hypophagia following chronic sulpiride treatment is not due to supersensitivity of D2 dopamine receptors in the lateral hypothalamus. Moreover, the change in the response to amphetamine might be related to supersensitivity of extrahypothalamic D2 receptors. PMID- 8516372 TI - Effects of long-term administration of clozapine on body weight and food intake in rats. AB - Previous reports have shown that long-term administration of typical and atypical neuroleptics induced obesity in female but not in male rats. It has been suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is necessary to observe the body weight changes. This hypothesis was tested with clozapine, an atypical neuroleptic that produces in rats a shorter increase in serum prolactin levels than do other neuroleptics. The effects of clozapine on body weight and food intake were assessed in female and male rats under treatment with any of the following doses: 0.5, 1, 2.5, 5, 10, and 20 mg/kg IP for 21 days. Vaginal cycle under clozapine treatment, as an indirect indicator of ovarian steroidogenesis, was also assessed. Obesity was not observed in any group. By contrast, clozapine at the doses of 10 and 20 mg/kg significantly decreased body weight and feeding in male rats. Clozapine at the doses of 5 and 10 mg/kg IP induced permanent diestrus. The failure of clozapine to induce obesity in female rats, despite impaired vaginal cycle, can be considered indirect evidence that drug-induced hyperprolactinemia is not sufficient to observe neuroleptic-induced obesity in rats. PMID- 8516373 TI - Effect of nootropic Solcoseryl on kainic acid-induced excitotoxic brain injury. AB - Solcoseryl (S) has been shown to provide significant cytoprotection in a variety of models of cerebral hypoxia. In the present study, we quantified the epileptiform effects caused by kainic acid administered into the pontine reticular formation of rats and their response to S pretreatment. Compared to saline, the agent appeared to significantly reduce the mortality of rats in the course of status epilepticus. However, S-pretreated rats manifested an increased incidence of behavioral seizures. This untoward effect is attributed to the fact that S improves the functional potential of injured tissue and retards the period of metabolic exhaustion at a time when neuronal activity should be minimized. PMID- 8516374 TI - Impairment and recovery under repeated doses of alcohol: effects of response outcomes. AB - This research examined the behavioral effect of alcohol during rising and declining blood alcohol concentrations (BACs) when the dose was repeated three times (mean peak BAC = 78 mg/100 ml). A total of 36 male social drinkers learned a complex psychomotor task and subsequently performed it at intervals after alcohol was received. Subjects performed under one of two conditions: an experimental (E) treatment associated drug-compensatory (nonimpaired) task performance with a positively reinforcing outcome or a control (C) treatment associated no environmental consequence with performance. E treatment diminished impairment at all positions on the BAC curve and carried over to result in progressively less impairment when the dose was repeated. In contrast, C treatment tended to increase impairment around the BAC curve with repeated doses. The rate of recovery during declining BACs remained stable across sessions and was not altered by the treatments. The results imply that impairment under a dose of alcohol is governed by two processes: response-outcome associations that determine the amount of impairment displayed under a dose and some adaptive process that determines the rate of recovery with time during exposure to a dose. PMID- 8516375 TI - Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice. AB - The effects of bilateral olfactory bulbectomy on serotonergic 5-HT2 and 5-HT1A receptor binding were studied in the frontal cortex (FC), limbic structures (LS), including the hippocampus, amygdala, olfactory tubercule, and piriform cortex, and hypothalamus (HTH) in mice. Bulbectomy resulted in the increase of Bmax for [3H]spiperone binding with 5-HT2 receptors in FC in C57Bl/6j. The receptors in LS and HTH remained unchanged. Subchronic treatment of the bulbectomized mice with antidepressant trazodone (20 mg/kg/day, IP, 14 days) induced downregulation of 5 HT2 receptors in FC and LS. The other two antidepressants used, amitriptyline (20 mg/kg/day, IP, 14 days) and imipramine (10 mg/kg/day, IP, 14 days), did not alter these receptors. [3H]8-OH-DPAT binding with 5-HT1A receptors was not altered by bulbectomy in any brain area in C57Bl/6j mice. Amitriptyline and trazodone decreased Bmax for these receptors in FC in the bulbectomized mice while imipramine was ineffective. Amitriptyline and imipramine significantly increased Bmax and decreased Kd in HTH, and trazodone displayed the same tendency. Bulbectomy did not alter 5-HT2 receptors in DBA/2j mice. Amitriptyline increased Kd in the all brain areas without changing Bmax in the bulbectomized DBA/2j mice. Trazodone significantly decreased Bmax in FC and increased Kd in FC and LS. Imipramine decreased Bmax while increasing Kd in LS. The possible involvement of the serotonin receptor subtypes in the bulbectomy-induced behavioral deficits and in the restorative action of the antidepressants is discussed. PMID- 8516376 TI - Modulation of [3H]flunitrazepam binding by natural and synthetic progestational agents. AB - Progesterone is metabolized by ring-A reduction with subsequent oxidoreduction to 3 alpha-hydroxy-5 alpha-dihydroprogesterone (3 alpha-OH-5 alpha-DHP), a naturally occurring metabolite that has been shown to enhance [3H]flunitrazepam ([3H]FNZ) binding. Medroxyprogesterone acetate (MPA), a commonly prescribed progestational agent, is a synthetic progesterone derivative that has a metabolic profile similar to that of progesterone. In this study, the effects of MPA and its ring-A reduced metabolites DHMPA and THMPA on [3H]FNZ binding were investigated. While known modulators of specific [3H]FNZ binding demonstrated expected effects in frozen and fresh rat cortical tissue, 3 alpha-OH-5 alpha-DHP enhanced [3H]FNZ binding only in fresh, not frozen, tissue. Neither DHMPA nor THMPA affected binding, while MPA partially inhibited [3H]FNZ binding by 40%. In addition, five test drugs were used to assess the effect of gender and hormonal status on [3H]FNZ binding. Neither gender nor hormonal status influenced binding. Thus, ring-A reduced metabolites of progesterone but not of MPA enhance [3H]FNZ binding. The clinical implications of these in vitro results are currently under investigation. PMID- 8516377 TI - Comparison of the satiating potencies of cholecystokinin-33 and cholecystokinin 8. AB - We investigated the satiating potency of CCK-33 and of CCK-8 administered IP to rats prior to a 30-min food intake test using a high-carbohydrate liquid diet. CCK-33 and CCK-8 produced dose-related inhibitions of intake. The ID50S and the slopes of the dose-response functions of the two peptides were not significantly different. We conclude that CCK-33 is as potent as CCK-8 for inhibiting food intake in the rat. PMID- 8516378 TI - Blockade of hippocampal nicotinic receptors impairs working memory but not reference memory in rats. AB - In a three-panel runway task, intrahippocampal injection of the nicotinic receptor antagonist, mecamylamine (10 and 18 micrograms/side), significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in a test of working memory. This increase in errors also occurred after rats were given IP mecamylamine (10 mg/kg). Mecamylamine did not affect the number of errors in a test of reference memory whether it was given at doses up to 18 micrograms/side intrahippocampally or up to 10 mg/kg IP. These results suggest that mechanisms mediated by hippocampal nicotinic receptors play a role in working memory but not in reference memory. PMID- 8516379 TI - Muscarinic cholinoceptor subtypes in the rat frontoparietal cortex after ipsilateral lesions of the nucleus basalis magnocellularis. AB - Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (M1) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM. PMID- 8516380 TI - Are m-cholinoceptors of guinea pig gallbladder smooth muscle of m4 subtype? AB - The antagonism of carbachol-induced contractions of guinea pig gallbladder smooth muscle strips via selective antagonists, methoctramine, HHSiD, pf-HHSiD and DABDMA has been investigated in order to find out the m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-cholinoceptor antagonists examined, displaced the concentration-response curves to the right parallel in a concentration dependent manner without affecting the maximum response. Schild analysis of data was consistent with competitive antagonism. -log KB values of the antagonists were 7.37 for HHSiD, 7.53 for pf-HHSiD, 6.58 for DABDMA and 7.60 for methoctramine. These results, together with the high affinity of pirenzepine and low affinities of 4-DAMP and AF-DX 116, indicate that the m-cholinoceptors of the guinea pig gallbladder which mediate cholinergic contractions are not of m1-, m2- and m3- subtypes but seem likely to be of m4-subtype. PMID- 8516381 TI - Effect of trimetazidine on mitochondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium. AB - The mitochondria harvested at the end of perfusion of control hearts and assayed for respiratory activity had a better function after ischemia and reperfusion following trimetazidine injection when glutamate was used as substrate. The protective effect of trimetazidine was enhanced when the mitochondria were isolated from hypertrophied perfused rat hearts. In fact the drug improved both the RCI and QO2 parameters with glutamate or succinate as substrates and raised the glutamate-induced QO2 value of mitochondria extracted from the hypertrophied heart perfused in aerobic conditions. In the aerobically perfused heart trimetazidine did not change either the levels of tissue malondialdehyde and lipofuscin, or the rate of mitochondrial O.2 generation while it reduced the O.2 formation and malondialdehyde content in the hypertrophied heart. After ischemia and reperfusion, the drug reproduced these protective effects in the hypertrophied hearts and reduced the level of tissue malondialdehyde in control hearts. The protective effect of trimetazidine against MDA formation was dose dependent, being more evident at a higher dose (10 mumol/l). Preincubation of rat heart mitochondria with 0.1-10 mumol/l trimetazidine did not affect NADH oxidase, NADH dehydrogenase and NADH-cytochrome c reductase, succinate oxidase and cytochrome c oxidase activities. These results indicate that trimetazidine injected into isolated rat hearts protects against the damage induced on cardiac energetics and oxidative injuries by moderate ischemia and reperfusion stress, particularly in monocrotaline-induced hypertrophy in the rat heart. We suggest that trimetazidine reduces the formation of oxidative damage by preserving cardiac mitochondrial function. PMID- 8516382 TI - Perception of the stop/glide contrast in infancy. AB - Much of the published research in infant speech perception has emphasized how well infants have done with a number of speech contrasts, and have noted similarities in pattern of discrimination of adults and infants. Often it has been suggested that infants begin life with the ability to perceive any speech contrast, and that the process of acquiring a language involves inhibition of the ability to perceive contrasts not present in the target language. Indeed some studies have shown infants able to discriminate contrasts on which adults fail if the contrasts are not drawn from the native language of the adults. Other studies, however, have suggested that infants may not always be so perceptually capable. The present work focusses on the stop-glide contrast. The results are inconsistent with the prevalent view and with previously reported studies on the perception of the stop-glide contrast by infants. The results indicate that in a vigilance paradigm adapted for both infant and adult testing, infants perform poorly on the contrasts when compared with adults. Furthermore the pattern of relative perception observed in the adults on stimuli with long or short vowels is quite unlike that of the infants. It is concluded that much work remains in order to evaluate the relative performance of infants and adults in speech perception, since it appears that changes in experimental paradigm or particular stimulus parameters may affect outcomes in fundamental ways. PMID- 8516383 TI - A multidimensional scaling study of voice quality in females. AB - In this study, a multidimensional scaling (MDS) analysis was performed to investigate perceptual discrimination by listeners among normal female voices. Speech pathologists and untrained listeners rated the similarity of all possible pairings of 20 female voices presented in sentences. MDS analyses were performed on these data. To interpret the resulting dimensions, listeners additionally evaluated each voice on each of 17 rating scales. For each listener group, the normalized and averaged perceptual ratings were correlated with MDS stimulus coordinates for the 20 voices. This procedure resulted in a five-dimensional solution which best explained the speech pathologists' similarity-dissimilarity judgements, with the following perceptual correlates for each dimension: (1) perceived pitch, (2) perceived loudness, (3) perceived age and duration of the speakers' stimulus sentence, (4) perceived variability, and (5) perceived quality. The untrained listeners' judgements were best explained by a two dimensional solution. Comparisons with other MDS studies were made, and the need for new acoustic measures was discussed. PMID- 8516384 TI - The effects of semantic context on voicing neutralization. AB - The present study examined regressive voice assimilation in Catalan in an attempt to determine a systematic explanation of complete versus incomplete voicing neutralization. Two types of contexts were constructed. In one type, semantic information was present to bias the meaning of target words. In the other type, no semantic information was present. The results showed that vowel duration distinguished underlying voicing in the neutral context only. The results suggest that neutralization occurs when semantic information is present, but that a voicing contrast is realized when it is absent. PMID- 8516385 TI - Orbitotemporal neurofibromatosis: classification and treatment. AB - In localized orbitotemporal neurofibromatosis, the treatment depends very much on the type and severity of the orbital involvement and on the functional state of the eye. The condition can be conveniently divided into three groups, each requiring different treatment: (1) orbital soft-tissue involvement with a seeing eye, (2) orbital soft-tissue and significant bony involvement with a seeing eye, and (3) orbital soft-tissue and significant bony involvement with a blind or absent eye. A total of 24 patients with a maximum of 12 years recurrence-free follow-up are presented. PMID- 8516386 TI - The anatomic basis of the anterior vaginal flap used for neourethra construction in female-to-male transsexuals. AB - For lengthening of the urethra in female-to-male transsexuals, an anterior vaginal wall flap is used. This flap is separated from the posterior urethral wall down to the attachment at the urethral meatus following a glistening cleavage plane. In this paper we present the anatomic and histologic basis of this flap. Prior to this, the relevant vaginal anatomy will be discussed. The anterior vaginal wall and posterior urethral wall are not indissectible structures; this is true even in the caudal two-thirds of the urethra. A long and narrow flap can be raised, thanks to the abundant vascular supply of the vaginal wall and the musculomucosal quality of the flap. A previously performed anatomic and histologic survey of the anterior vaginal wall has shown that the glistening cleavage plane is not composed solely of fascia, but rather consists of longitudinal strands of muscle, fibrous tissue, and elastin. PMID- 8516387 TI - Surgical correction of the Treacher Collins malar deficiency: quantitative CT scan analysis of long-term results. AB - This paper describes an alternative means of reconstruction of the Treacher Collins zygomatic deficiency and presents a consecutive patient series with long term follow-up documented by clinical and quantitative means employing CT-derived craniofacial skeletal measurements. Eight children (mean age at operation 10.5 years) underwent bilateral zygomatic reconstruction with full-thickness, T-shaped calvarial bone grafts contoured three-dimensionally and then inset and stabilized with plate-and-screw fixation, with exposure provided only by a coronal incision. Orbital floor defects and graft donor sites were repaired with fixed split thickness cranial bone. No complications occurred during surgery, and donor sites healed without clinical defect. Zygomatic augmentation was achieved in all patients, with follow-up ranging from 24 to 50 months (mean 35 months). CT scanning done before surgery, immediately afterward, and again 1 year or more later demonstrated significant increases in lateral orbital wall length, lateral orbital distance, interzygomatic arch distance, and zygomatic arch length. The late postoperative scans showed that these changes were maintained. However, effective treatment of the surrounding soft-tissue and eyelid deficiencies remains an unsolved problem. PMID- 8516388 TI - Deferoxamine attenuates ischemia-induced reperfusion injury in the skin and muscle of myocutaneous flaps in the pig. AB - The dose effect of deferoxamine treatment in attenuation of ischemia-induced reperfusion injury in the skin and muscle of latissimus dorsi myocutaneous flaps was studied in pigs weighing 19.7 +/- 0.5 kg. The latissimus dorsi myocutaneous flaps were subjected to 4, 6, or 8 hours of warm global ischemia. The length and area of viable and nonviable skin and muscle were assessed 48 hours after the ischemic insult by using the fluorescein and nitroblue tetrazolium dye tests, respectively. It was observed that perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of ischemia-induced reperfusion injury in the skin but not in the muscle of latissimus dorsi myocutaneous flaps subjected to 4, 6, or 8 hours (n = 10) of ischemia compared with the saline treated control (n = 10). In a separate study, it was observed that preoperative deferoxamine treatment (250 mg/kg per day x 2 days, IM) plus perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of muscle ischemia-induced reperfusion injury in latissimus dorsi myocutaneous flaps subjected to 4 hours of ischemia and 48 hours of reperfusion (n = 10) compared with the saline treated control (n = 10). Morphologic studies with light and electron microscopy also provided evidence to indicate that preoperative plus perioperative deferoxamine treatment, but not perioperative deferoxamine treatment alone, remarkably reduced ischemia-induced reperfusion injury in the skeletal muscle of latissimus dorsi myocutaneous flaps compared with the saline treated control. It is concluded that deferoxamine is effective in the attenuation of ischemia-induced reperfusion injury in the skin and muscle of pig latissimus dorsi myocutaneous flaps, but a longer period and/or higher dose of deferoxamine treatment is required for the muscle than for the skin. The pharmacologic actions and metabolism of deferoxamine relating to mitigation of ischemia-induced reperfusion injury in the pig skin and muscle are discussed. PMID- 8516390 TI - Swimming upstream. PMID- 8516389 TI - Effective teaching in the operating room. PMID- 8516391 TI - Simultaneous maxillary and mandibular reconstruction with one free osteocutaneous flap. AB - The concept of immediate reconstruction of massive facial injury with rigid internal fixation and free-tissue transfer continues to evolve. This case is unique in that it is the first report of the following: (1) simultaneous combined maxillary and mandibular reconstruction with one vascularized bone graft and (2) immediate total maxillary reconstruction with vascularized fibular bone. The nasopharynx was closed with a tubed radial forearm flap. Reconstruction was staged over several days, with dissection/banking of flaps, grafts, recipient sites, and debridement as a preliminary stage. PMID- 8516392 TI - Subepineural hyperplastic pacinian corpuscle: an unusual cause of digital pain. AB - A case is presented in which the patient's chief complaint was severe digital pain radiating to the arm. Even light touch was enough to produce unbearable pain, which prevented the patient from carrying out simple daily tasks. She had complete relief of her symptoms following removal of the hyperplastic pacinian corpuscle and returned to her normal life. A review of the literature revealed few reported cases of hypertrophied pacinian corpuscles in the hand. We believe that this diagnosis must be considered in the differential diagnosis of digital pain of unknown etiology. PMID- 8516393 TI - Disposable implant injector with expandable outlet. AB - A disposable breast implant injector with expandable outlet is presented. This new injector is convenient to use and prevents cross-infection. There is also a lower chance of contamination from axillary skin. The expandable outlet allows decreased resistance during injection and therefore reduces injection time and lowers the chance of damage or rupture of the implant. The injector also works well for both smooth and textured prostheses. PMID- 8516394 TI - Sculpturing the glans in phalloplasty. AB - One of the goals of phalloplasty is the construction of an aesthetically appealing neophallus with a urethral meatus at its tip. Aesthetic considerations imply the creation of a glanslike structured tip. A review of the scarce literature on sculpturing of a glans is given. In cases in which microsurgical free-flap techniques are applied in our hospital, the glans is usually sculptured to its final appearance during the actual phalloplasty. If, on the other hand, an abdominal or inguinal skin flap is used, final sculpturing will be done as a subsequent separate procedure. From a review of the literature on this subject and from our experience, one may conclude that the Norfolk technique of coronal ridge and sulcus construction has best results. We consider Munawar's technique to be obsolete, since it tends to lead to flattening of the coronal ridge. PMID- 8516395 TI - Anesthesia for tongue flaps in infants. PMID- 8516397 TI - A guide to emergency room jargon. PMID- 8516396 TI - AIDS and aesthetic surgery. PMID- 8516398 TI - Hand infection splint and postoperative elevation. PMID- 8516399 TI - The application of duplex ultrasonography in the preoperative evaluation of patients prior to TRAM flap reconstruction. PMID- 8516400 TI - Liposuction to radiologist's rescue. PMID- 8516401 TI - Microscopic demonstration of intraductal extension of silicone from a ruptured breast implant. PMID- 8516402 TI - Bedside polysomnography as an adjunct in the management of infants with Robin sequence. AB - Objective indications for tongue-lip adhesion in infants with Robin sequence have been lacking because of the difficulty in assessing the clinical significance of airway obstruction. In 1988, we began to use 20-hour, four-channel polysomnography to assist us in the management of infants with Robin sequence. The four channels included electrocardiogram, respiratory motion, airflow, and oxygen saturation. Infants demonstrating significant episodes of airway obstruction during sleep were recommended for tongue-lip adhesion. Fifteen infants with Robin sequence were evaluated during a 3-year period. Two babies were having severe, clinically obvious events on admission and underwent tongue lip adhesion without polysomnography. Polysomnography was done on the other 13 infants. No significant events were seen in 7 infants, and they were discharged after a mean hospitalization of 8 days. Six studies documented significant airway obstruction, and tongue-lip adhesion was recommended. Follow-up polysomnography performed after successful tongue-lip adhesion failed to show any significant events, and the infants only required hospitalization for a mean of 12 days. We conclude that polysomnography is a useful adjunct in the management of infants with Robin sequence, providing objective indications for surgical intervention and shortening hospitalization. PMID- 8516403 TI - The role of orbital ultrasound in the diagnosis of orbital fractures. AB - The role of CT scanning in the diagnosis and management of craniomaxillofacial injuries is well documented. However, coexistent injuries, limitations on patient positioning, CT availability, or financial constraints may prevent or delay the diagnosis of significant orbital wall defects. Real-time ultrasound represents a safe, inexpensive, noninvasive, portable, and readily available diagnostic modality which has had a limited application in the diagnosis of orbital pathology. The objectives of this study were to define the role of orbital ultrasound in the assessment of the traumatized orbit and to provide correlation of pathology with CT imaging. Eighteen patients (16 males, 2 females) having sustained trauma to the orbitozygomatic region were assessed at a regional trauma center over a 6-month period. Each patient underwent an ultrasound examination of both orbits. Confirmatory CT scans (5-mm axial and 1.5-mm coronal orbital cuts) were then obtained for comparative assessment. Patients with open globe injuries, alteration of visual acuity, or life-threatening conditions were excluded from the study. The results of the study revealed a positive correlation between the ultrasound and CT findings in 17 (94 percent) of the patients. Ultrasound demonstrated satisfactory sensitivity (92 percent) and specificity (100 percent) and positive predictive value (100 percent) when compared with CT scanning. Soft tissue herniation, orbital emphysema, and muscle entrapment were well visualized by means of real-time ultrasound. It is concluded that orbital ultrasound is an accurate diagnostic modality in the investigation of orbital trauma and correlates well with CT findings. A cost analysis will be presented, and details of the limitations and efficacy of orbital ultrasound will be discussed. PMID- 8516404 TI - Long-term results of blunt suction lipectomy assessed by a patient questionnaire survey. AB - A questionnaire was sent to 1339 consecutive patients who had undergone blunt suction lipectomy during the period between April 1984 and April 1987. Seventy four percent replied, thus providing information about the results of 1929 procedures. The overall reported rate of satisfaction was 76 percent, with no significant difference between males and females. Highest satisfaction referred to pseudogynecomastia, submental area, iliac crest, and lower extremities on females. The rate of dissatisfaction was 6 percent. Dissatisfaction was associated most frequently with lipectomy of the buttocks. Underresection was reported for 30 percent and over-resection for 2.2 percent of the procedures. The latter, in particular, seemed to lead to dissatisfied patients. Asymmetry was reported for 19 percent of the procedures. Recurrence ("return") of fatty tissue was reported for 29 percent at the resection site. Thirty percent of the patients reported compensatory increase ("came back elsewhere") in fat deposits in nontreated locations. Self-reported weight gain was found to be a significant risk factor for both types of "regrowth." Irregularities were the most frequently reported permanent changes to skin. There were twice as many negative as positive changes to skin. Most of the patients had benefited personally from the surgery and were willing to consider undergoing lipoplasty again. All in all, the long term results of blunt suction lipectomy are satisfactory. PMID- 8516405 TI - A study of the arterial supply in the human rectus femoris muscle. AB - The rectus femoris muscles have been used in reconstructive surgery, although their vascular anatomy has not been examined in detail. Thus, using cadavers, we have analyzed the extramuscular vascular pattern of 40 rectus femoris muscles and the intramuscular vascular pattern in 27 of these 40 muscles by means of an injected radiopaque substance and subsequent arteriography. The arterial patterns seen, depending on their relationship to the intramuscular tendon, then were classified as follows: type 1a (13 muscles), type 1b (3 muscles), type 2 (7 muscles), and type 3 (4 muscles). In the type 1a pattern, most of a muscle belly was supplied by one artery, but this was not seen in the other pattern types. We also observed an average of 2.6 musculocutaneous perforators. Therefore, in planning a free muscle transfer, the anatomic characteristics of the muscle should be kept in mind. PMID- 8516406 TI - The surgical anatomy of the principal nutrient vessel of the tibia. AB - Large segmental long-bone defects deserve consideration for reconstruction by vascularized, straight, high-density cortical bone grafts of comparable diameter. If available, the tibial diaphysis would be an option superior to the fibula, since the latter has known limitations when a large size discrepancy exists at the recipient site. However, the former choice is unrealistic except in the most unusual circumstances, since the tibia is a nonexpandable bone required for weight bearing. In anticipation of just such a unique opportunity, we have investigated the surgical anatomy of the principal nutrient vessel of the shaft of the tibia in 53 fresh lower limb specimens. Classical descriptions of the pertinent vascular anatomy of the tibial shaft are inadequate, since the origin of its principal nutrient vessel actually may be from the popliteal bifurcation or anterior or posterior tibial vessels. In every dissection at least a single artery and vein of large caliber (both exceeding 1.5 mm in diameter in 85 percent of cadavers) were discovered entering a nutrient foramen, usually at the upper third of the tibia. Lead oxide injection studies of the nutrient artery alone in nine cadavers demonstrated no contiguous muscle or cutaneous communications. The large size of these nutrient vessels would simplify ipsilateral pedicled transfers of an autologous tibial shaft as well as facilitate microanastomoses for its distant transfer to other humeral, femoral, or contralateral tibial defects as in a salvage replantation. Once immunologic barriers have been conquered, these data should have even greater practical clinical significance for the use of vascularized tibial allografts for substitution in lieu of autogenous fibula or other conventional bone donor sites. PMID- 8516407 TI - The long head of the biceps femoris: anatomic basis for its possible use in the construction of an electrically stimulated neoanal sphincter. AB - Electrical stimulation of the nerve to the gracilis muscle following its transposition around the anal canal creates an artificial sphincter capable of actively opposing intrarectal pressure. Not all patients have an available or suitable gracilis. This paper describes the anatomic basis for the use of the long head of the biceps femoris as a potential electrically stimulated neoanal sphincter. The muscle was found to have an adequate length and a suitable arc of rotation for transposition around the anal canal. In 75 percent of thighs studied the neurovascular anatomy of the long head of the biceps femoris was compatible with its utilization in this manner as an alternative to the gracilis. PMID- 8516408 TI - Expanded full-thickness skin grafts in children: case selection, planning, and management. AB - Since our initial presentation of our experience with tissue expansion as a means of harvesting large full-thickness skin grafts in children in 1987, we have continued to "expand" both the size of full-thickness skin grafts harvested and the range of reconstructive problems to which we have applied the technique. Sixteen expanded full-thickness grafts have been used for immediate reconstruction following giant nevus excision and in postburn reconstruction. Patients ranged in age from 6 months to 15 years, with follow-up ranging from 6 months to 6 1/2 years. Grafts ranging in size from approximately 60 cm2 (excluding the dimensions of one submental graft) to greater than 700 cm2 were harvested from expanded donor sites on unilateral or bilateral groin/lower abdomen, clavicular, and a single submental expansion. Five expanded full thickness grafts were used in facial reconstruction for single aesthetic unit coverage, multiple unit, and one single-sheet full facial graft. One expanded full-thickness graft was used on the breast. Three grafts were used in dorsal hand and finger coverage, and seven were used on the lower extremity, including an entire plantar surface and toes. Graft loss was confined to a 6.25-cm2 area on one cheek in the full facial expanded full-thickness grafts and a 9-cm2 area on the non-weight-bearing area of the full plantar graft. Donor-site complications were negligible. The anatomic confines of the donor sites and size of the patient may require expander replacement (in situ serial expansion) in order to obtain a large enough graft and accomplish primary donor-site closure. Expander and injection port placement in children for ease of injection and planned expander change must be anticipated. Our protocol from preoperative teaching through graft take is reviewed. Experience has demonstrated that expanded full-thickness grafts maintain all the characteristics of non-expanded full-thickness skin grafts and are an excellent reconstructive option in children. PMID- 8516409 TI - Relative donor-site morbidity of muscle and fascial flaps. AB - Accusations of excessive donor-site morbidity as an unavoidable sequela of fasciocutaneous flaps has negatively prejudiced this option for coverage of adjacent defects such that a muscle flap, if available, would instead be preferable even at the risk of loss of marginally expendable function. Our entire experience with 147 juxtaposed muscle-type and 122 fascia-type flaps was analyzed to confirm instead that actual donor-site morbidity was extremely uncommon for either type. Overall, there were 20 (14 percent) complications of the donor site of muscle flaps and 17 (14 percent) for fascial flaps, with only 4 (3 percent) major complications in each group. This almost minuscule incidence of major morbidity was about five times less than the rate of major complications involving the flaps themselves (14 percent for muscle and 15 percent for fascial flaps). Unless aesthetic considerations are of paramount importance, at least from a functional standpoint, no difference in donor-site complications could be discerned between these two disparate flap types. However, the skin-grafted donor site of the fasciocutaneous flap results in a significant cosmetic disadvantage similar to that of a large musculocutaneous flap. PMID- 8516410 TI - Various methods of breast reconstruction after mastectomy: an economic comparison. AB - This study is an economic comparison of various methods of breast reconstruction after mastectomy. The hospital bills of 287 patients undergoing breast reconstruction at three institutions from June of 1988 to March of 1991 were analyzed. The procedures examined included mastectomy, implant and tissue expander reconstruction, and TRAM and latissimus pedicle flaps, as well as free TRAM and free gluteal flaps. These procedures were subdivided into those which were performed at the time of mastectomy and those performed at a later admission. In addition, auxiliary procedures (i.e., revision, nipple reconstruction, tissue-expander exchange, and contralateral mastopexy/reduction) also were examined. Where appropriate, these procedures were subdivided into those performed under general or local anesthesia and by inpatient or outpatient status. Data from the three institutions were converted to N.Y.U. Medical Center costs for standardization. A table is presented that summarizes the costs of each individual procedure with all the pertinent variations. In addition, a unique and novel method of analyzing the data was developed. This paper describes a menu system whereby other data regarding morbidity, mortality, and revision rates may be superimposed. With this information, the final cost of reconstruction can be extrapolated and the various methods of reconstruction can be compared. This method can be applied to almost any complex series of multiple procedures. The most salient points elucidated by this study are as follows: The savings generated by performing immediate reconstruction varies between $5092 (p < 0.05) for free gluteal flaps and $10,616 (p < 0.05) for pedicled TRAM flaps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516411 TI - The continuous elongation treatment by the TEC device for severe Dupuytren's contracture of the fingers. AB - The continuous elongation technique is a preparatory step for excision of the pathologic palmar fascia for severe Dupuytren's contracture of the hands. It consists of a physiologic, painless, and atraumatic elongation that is obtained by means of a device fixed on the fourth and fifth metacarpal bones by two self drilling pins. This paper presents our experience since 1986 with the TEC device, which we designed and built for severe hand contracture; the device has been applied on 56 hands and 85 fingers seriously flexed by Dupuytren's contracture. This advanced methodology also represents a real alternative to the surgical indication of finger amputation in progressive cases of the fascia retraction, and it avoids the necrosis, loss of vascularity, and bad functional results frequently seen after classical operations. The TEC device also avoids the plastic surgical correction of digital or palmar skin loss, particularly when there is a need for a flap or a skin graft. Dupuytren's contracture was for 160 years thought to be degenerative, progressive, and irreversible, but the TEC device, by bringing the contracture back to the initial stage of the disease, opens up new basic research into morphologic and biochemical processes of the collagen in the retracted palmar fascia. PMID- 8516412 TI - The serratus anterior free-muscle transplant for reconstruction of the injured hand: an analysis of the donor and recipient sites. AB - The present study evaluated donor-site function in eight patients for whom serratus anterior free-muscle transplantation was performed to treat a traumatic defect of the palm. The lowest two or three slips of the muscle were transferred from the uninjured side and covered with split-thickness skin grafts. After an average follow-up period of 50 months (range 13 to 84 months), function and appearance of the flaps were assessed, and shoulder strength on the donor side was objectively tested in six patients by using an isokinetic computerized robotic dynamometer. No patient noticed any change in upper extremity function following the procedure. Each of the three patients in whom three slips had been taken displayed mild scapular winging, but none complained of any related symptoms. Neither push strength nor abduction strength on the donor side was significantly different compared with that on the recipient side. The transplanted muscle provided excellent contour and durable cover in all eight hands with limited donor-site morbidity. For this reason, the serratus anterior transplant is our flap of choice for the treatment of large palmar defects. PMID- 8516413 TI - [Acute psychoses in adult patients with mild mental retardation]. PMID- 8516414 TI - No chronic hyperventilation in panic disorder patients. AB - Arterial blood gases were measured and base excess calculated in 18 nonpanicking panic disorder (PD) patients, 12 subjects suffering from other anxiety disorders, and 18 normal control subjects. There was neither chronic nor clinically significant acute hyperventilation in either group. PMID- 8516415 TI - Electrodermal activity in relation to basal and postdexamethasone levels of thyroid stimulating hormone and basal levels of thyroid hormones in major depressive patients and healthy subjects. AB - Electrodermal activity in 50 patients with major depression and 50 matched healthy control subjects was related to basal and postdexamethasone changes in levels of thyroid stimulating hormone (TSH), basal levels of thyroid hormones, and nocturnal levels of urinary cortisol. Levels of skin conductance and thyroxine were inversely correlated in the patients, but positively correlated in the healthy subjects. Patients with blunted postdexamethasone reduction of TSH showed high rates of nonevoked electrodermal fluctuations, low TSH levels, and elevated nocturnal urinary cortisol levels. PMID- 8516416 TI - Case identification and stability of the deficit syndrome of schizophrenia. AB - In certain situations, such as large epidemiological studies, it may be necessary to use proxy case-identification tools instead of "gold-standard" assessments. The deficit syndrome of schizophrenia requires a clinical assessment that may not be feasible in some study populations. Measures for the discrimination of deficit and nondeficit patients, based on the Brief Psychiatric Rating Scale (BPRS), were assessed in a group of 100 outpatients with chronic schizophrenia. A rationally based case-identification tool was validated, and its case-identification properties were found to be stable over time; consequently, this proxy measure may be of use in other data sets. The stability of the relationship between this BPRS measure and the deficit/nondeficit categorization supports the view that it is a valid categorization. PMID- 8516417 TI - Platelet serotonin levels in alcoholic patients: changes related to physiological and pathological factors. AB - This study investigated platelet serotonin (5-hydroxytryptamine; 5-HT) levels and the effects of different physiological and pathological factors in 108 alcoholic patients (alcohol abuse, n = 49; alcohol dependence, n = 59) and 32 healthy control subjects. Platelet 5-HT levels were determined by a fluorescent-ortho phthalaldehyde assay. In patients, platelet 5-HT levels during withdrawal from alcohol and after 2 weeks of abstinence were significantly lower than in control subjects. Among patients, this decrease was enhanced both in alcohol-dependent patients and in patients who were depressed during the withdrawal phase, whereas lifetime impulse control disorders (mostly found in alcohol abusers) were associated with comparatively high platelet 5-HT levels (i.e., close to control subjects' values). These results, which reflect the likely biphasic effect of alcohol ingestion upon 5-HT functioning, are consistent with the dimensional 5-HT hypothesis in psychiatric disorders. PMID- 8516418 TI - Motoric signs of CNS dysfunction associated with alcohol and cocaine withdrawal. AB - Measures of hand tremor and body sway were recorded from 6 alcohol-dependent (AD) and 16 cocaine-dependent (CD) patients after 1, 3, and 12 weeks of verified abstinence. The same measures were recorded from 15 nonpatient control subjects after comparable intervals. Hand tremor was transduced via an accelerometer. Body sway was transduced by a force-sensitive platform. Analyses revealed different patterns of motoric dysfunction in the AD and CD groups. AD patients exhibited enhanced hand tremor during a pointing task and enhanced body sway. Both of these abnormalities remitted with continued abstinence. CD patients exhibited enhanced and unchanging levels of resting tremor across the first 12 weeks of abstinence, but they had normal levels of body sway and action tremor. These results are interpreted as reflecting a subclinical cerebellar dysfunction in recovering AD patients, and a subclinical extrapyramidal dysfunction in the CD counterparts. PMID- 8516419 TI - The hypothalamic-pituitary-thyroid axis in depressive patients and healthy subjects in relation to the hypothalamic-pituitary-adrenal axis. AB - Serum levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), free T3 index (fT3i), thyroxine (T4), and free T4 index (fT4i) were measured before and after administration of 1 mg of dexamethasone in 54 depressive patients and 54 matched healthy subjects. A followup study at a mean of 2 years was performed in 28 patients in remission. Basal TSH levels were lower and fT4i levels were higher in major depressive patients compared with healthy subjects. After dexamethasone administration, there was no significant change in any of the hormones in a subgroup of 46 major depressive patients in contrast to matched healthy subjects, who showed a significant decrease in the levels of TSH, T3, and fT3i. The magnitude of the TSH response to dexamethasone in the major depressive patients was related to the level of nocturnal urinary cortisol excretion and pathological dexamethasone suppression test results. The level of TSH in depressive patients during remission did not return to levels similar to those found in the healthy subjects. PMID- 8516420 TI - Spontaneous eye blink rate in winter seasonal affective disorder. AB - We investigated spontaneous eye-blink rates in 19 drug-free patients with winter seasonal affective disorder (SAD) and 18 normal control subjects. At baseline, there were no significant differences between the two groups (mean +/- SD blink rate: 15/minute +/- 8 vs. 15/minute +/- 7). Light therapy (10,000 lux: 1 hour each morning for 1 week) produced no significant change in mean (+/- SD) blink rates either in 10 SAD patients (13/minute +/- 8 vs. 10/minute +/- 7) or in 12 normal control subjects (15/minute +/- 6 vs. 14/minute +/- 6). A post hoc exploratory analysis of the effect of light therapy on premenopausal female subjects (5 patients and 9 control subjects) showed a significant decrease in mean (+/- SD) blink rate in the patients after treatment (17 +/- 6 vs. 12 +/- 8 compared with 15 +/- 7 vs. 16 +/- 5). These results do not support the idea that an elevated blink rate may be a general biological marker in SAD, but they suggest a possible link between light treatment and mechanisms that regulate blink rate in premenopausal SAD patients. PMID- 8516421 TI - Effects of bright light on mood in normal elderly women. AB - Reduced light appears to be a key factor in seasonal affective disorder (SAD). This study asks whether the reduced levels of light experienced by elderly persons might result in depression and other SAD symptoms, and how normal elderly persons might respond to bright light interventions similar to those used to treat SAD. In interviews with 140 senior citizens, we found virtually no seasonal variation in mood and behavior and very little depressed affect. Seventeen of these seniors who had good mental and physical health, with no major eye problems, participated in a crossover study of the effects of bright light on both positive and negative affect and sleep. Although sleep did not appear to be affected, the bright light intervention tended to make these normal elderly persons feel worse--more irritable, anxious, and agitated. These findings confirm earlier reports that bright light is not beneficial for normal individuals who are unaffected by seasonal changes. PMID- 8516422 TI - Hemispheric language lateralization in seasonal affective disorder and light treatment. AB - Thirty-seven patients with seasonal affective disorder (SAD) and 25 control subjects were given a concurrent task, the verbal-manual interference paradigm, as a measure of hemispheric language lateralization. In winter, depressed patients showed a symmetrical interference pattern and control subjects experienced greater overall disruption in right-hand tapping during concurrent verbalization. Patients showed a greater left-hand tapping decrement compared with control subjects. Light treatment decreased the decrement in tapping with the left but not with the right hand in patients. After treatment, patients did not differ from controls in dual task interference effects. Patients also showed no difference from controls in summer. The difference between depressed subjects and controls in performance measures of laterality suggests that winter depression is associated with a shift of laterality from the left to the right. The winter abnormalities appear to be normalized by bright light. PMID- 8516423 TI - GH secretion status in myotonic dystrophy. AB - Frequent endocrine alterations and abnormal growth hormone (GH) secretion have been reported in myotonic dystrophy (MD). To evaluate GH secretion status in MD, GH response to 100 micrograms of growth hormone releasing hormone (GHRH) with or without pyridostigmine pretreatment and its relation with insulin-induced hypoglycemia was investigated in MD patients and compared with normal controls. The mean peak plasma GH response to GHRH was 27.8 +/- 19.2 micrograms/l normal subjects and 11.4 +/- 8.7 micrograms/l in MD patients. In five of seven patients GH reached a mean peak of 12.6 +/- 4.2 micrograms/l after insulin-induced hypoglycemia, compared with 5 +/- 2.8 micrograms/l after GHRH. Conversely, in two patients GH reached a peak of 16.1 and 32 micrograms/l after GHRH, and only 2.5 and 5.3, respectively, after hypoglycemia. Pretreatment with pyridostigmine in nine patients tested potentiated GHRH-induced GH release with a peak of 17.6 +/- 12.5 micrograms/l, compared with 10.05 +/- 6.7 micrograms/l after GHRH alone; IGF I levels were normal in all patients. PMID- 8516424 TI - LH pulsatile secretion and testosterone blood levels are influenced by sexual arousal in human males. AB - To determine whether changes in LH and testosterone (T) blood levels and pulse signals were induced by sexual arousal, nine healthy young males were presented on two different days with a sexually arousing (S) and a sexually neutral control (C) film. On both sessions, blood was sampled every 10 min for 12 hr. The Cluster and the Detect pulse identification algorithms were used to characterize the peaks in LH and T series. The second plasma LH peak following the beginning of the film was higher in the S than in the C condition (percent increases above preceding nadir: 322.1 +/- 183.9% vs. 202.6 +/- 108.7%). The area of the second pituitary peak of LH instantaneous secretion rate, which corresponded to the second plasma LH peak, was also greater in the S condition (6.2 +/- 3.3 vs. 3.4 +/- 2.3 UI/l). Compared with the C condition, T blood levels were increased within the first 10 min of sexual arousal (25.2 +/- 6.3 vs. 22.2 +/- 5.6 nmol/l). These results, consistent with the findings of animal studies, indicate that LH pulsatile secretion and T blood levels are influenced by changes in the state of sexual arousal in human males. PMID- 8516425 TI - Cortisol reactivity and anxiety and depression in pregnant adolescents: a longitudinal perspective. AB - The purpose of this investigation was to examine: (1) the relations among cortisol reactivity (short term changes in cortisol concentration) and anxiety and depression symptoms in adolescents during pregnancy and early postpartum, and (2) cortisol reactivity and psychosocial variables as predictors of anxiety and depression symptoms in pregnancy and early postpartum. Cortisol reactivity, an index of hypothalamic-pituitary-adrenal activity, was hypothesized to be a vulnerability factor for poor physical and mental health outcomes in adolescents. Forty adolescents aged 14 to 19 years (M = 17.3, SD = 1.3) were enrolled in the study and were seen at < 20 weeks gestation (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood was drawn for cortisol at T1 and T3. Psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered at T1, T2, and T3. There were significant correlations among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but the correlations were the reverse of the hypothesized direction. Pregnant adolescents with increased cortisol reactivity (cortisol concentrations that increased across a 40-min period) had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses showed that anxiety and depression symptoms at T1 were a stronger predictor of postpartum anxiety and depression than was cortisol reactivity, life optimism, self-worth, or age at pregnancy. PMID- 8516426 TI - Initial study of back pain among radiographers. AB - Researchers surveyed state professional radiography organization members to document incidence of back pain, demographic data and preferences for performing radiography tasks. Six of the routine radiography tasks included in the survey were performed the same way by radiographers with back pain and those without back pain. Four of the tasks were performed differently by the two groups of radiographers. Applying biomechanical principles to radiography clinical situations may increase radiographers' awareness of, and decrease the incidence of, occupational back injury. PMID- 8516427 TI - Administrators evaluate bachelor's degrees for R.T.s. AB - This article reports the results of a survey conducted to assess radiology administrators' attitudes regarding a bachelor of science degree for radiography students. Administrators at accredited hospitals in Nevada, Utah and Arizona were asked whether they believed a bachelor's degree would benefit radiographers in terms of status, employment, salary and placement in the health care industry. The survey results were mixed, showing no overall consensus in willingness to pay higher salaries to those with a bachelor's degree and no preference for hiring a radiographer with a bachelor's degree over one with an associate degree or hospital training. PMID- 8516428 TI - Entry-level standards for MRI technologists. The ASRT Task Force on Entry-Level Standards for Magnetic Resonance Technologists. AB - This special report describes the findings of two surveys designed to identify MRI technologists' opinions about entry-level standards. The surveys were conducted by the ASRT Task Force on Entry-Level Standards for Magnetic Resonance Technologists. Results show that MRI technologists believe those entering the profession should be registered radiologic technologists or Registry-eligible and should have formal MRI education. PMID- 8516429 TI - A touchstone for program quality. PMID- 8516430 TI - Ideas for interactive classroom learning. PMID- 8516431 TI - Health care reform and mammography. PMID- 8516432 TI - Japanese RTs struggle for professional status. PMID- 8516433 TI - [Breast cancer screening. State of the art and introduction to preventive measures]. AB - Carcinoma of the breast is the most frequent cause of death in women aged between approximately 38 and 50 years. At present, 1 out of 14 women in Germany and 1 out of 9 in America suffer from breast cancer within a life time. To date, modern methods of treatment and hormone therapy have only been able to increase long term survival by about 12%. Trials have shown that early diagnosis alone has been able to increase survival from 20% to 50%. Early diagnosis proved to be most effective when clinical examination plus mammography in two planes was carried out annually. An increase in survival has been achieved in post-menopausal women as a result of screening. 22 percent of breast cancers were detected at a curable in situ stage by means of screening. Even after a limited screening program of 4 examination cycles the increase in survival rate over 15-20 years was significant. PMID- 8516434 TI - [The pathology of mastopathy and breast cancer]. AB - Radiologists and pathologists play the most important role in the diagnosis of breast diseases. The combination of mammographic and cytological investigations can lead to the determination of which lesions require an operation and which do not. Fibroadenomas, mastopathies and carcinomas are the most common histological diagnoses. It is necessary to decide which type of mastopathy (atypical intraductal or intralobular hyperplasia) might involve a higher risk of carcinoma. When classifying carcinomas, the pathologist must give details about prognostic factors such as staging (pTN status), histological typing, grading, and hormone receptors (oestrogen and gestagen). PMID- 8516435 TI - [The technique and results of mammography]. AB - In the field of mammography, technical progress has been achieved and successfully implemented in routine practice in the last few years. The diagnostic value of mammography has been re-assessed in numerous studies. Breast conserving therapy of breast carcinoma has posed new pre- and postoperative diagnostic tasks. The introduction of mammography into a future national breast cancer detection program will present a challenge for many mammographers in several aspects. Radio-epidemiological doubts about introduction of mammographic screening are in-substantial. PMID- 8516436 TI - [Digital magnification mammography. A new technique for improved visualization of microcalcifications in breast cancer diagnosis]. AB - Special X-ray tubes with electromagnetic focusing provide a spatial resolution of up to 50 lp/mm at a focal spot size of about 10 microns. Radiographs of whole female breast specimens as well as paraffin blocks were taken at magnifications up to x 10. The initial results revealed numerous microcalcifications smaller than < 100 microns that had not been detected by conventional grid mammography. The combination of a microfocal spot with digital radiography results in as yet unmatched resolution of microcalcifications and makes the advantages of image post-processing available to mammography. However, specific types of calcification could not be established in malignant or benign histological findings. PMID- 8516437 TI - [Clarification of breast lesions using core-cut, drill and fine needle biopsy]. AB - Interest in needle biopsy methods (core cut-, drill-, and fine-needle biopsy) has recently increased considerably because of the rise in screening mammography and new developments in the therapy of breast cancer. In order to achieve adequate results using needle biopsy and to avoid complications, certain technical details must be strictly adhered to. An experienced surgeon can achieve a sensitivity of above 90% in the diagnosis of breast carcinoma with all three methods. Considering the advantages and disadvantages of these three methods of needle biopsy, we prefer--based on our own experience--high-speed core-cut biopsy for the morphological evaluation of breast lesions. PMID- 8516438 TI - [Localization of non-palpable lesions by mammography for preoperative marking and tissue removal]. AB - Mammography screening can increase survival by 15-50%. Minute nonpalpable breast carcinomas can be detected and surgically removed using precise localization techniques. Various techniques are shown, including localization by means of grid mammography and conventional localization with several needles. Stereotactic localization is recommended if the focus cannot be detected by sonography--a procedure now almost always possible if mammography units have the necessary additional equipment. In future it will often become necessary, following a good response to pre-operative chemotherapy, for the tumor, which as a result has become nonpalpable, to be marked prior to surgery (e.g. remaining microcalcifications). This is essential if a representative area of tissue is to be made available for histological examination. PMID- 8516439 TI - [Magnetic resonance spectroscopy of breast cancer]. AB - Conservative therapeutic concepts with initial chemotherapy for patients with breast cancer represent a challenge to non-invasive techniques for monitoring response to therapy. Experimental magnetic resonance spectroscopy studies have been able to show exemplary applications for therapy monitoring of breast cancer patients. The characteristic phosphomonoester resonances and their changes during therapy are possible clinical parameters. The additional information which can be obtained from proton and carbon spectroscopy increases the amount of detectable metabolites. On-going studies are investigating clinical applications of multinuclear spectroscopic studies in patients with breast cancer. PMID- 8516440 TI - [Superselective intra-arterial chemotherapy in breast cancer]. AB - Forty-two patients with locally advanced breast cancer (n = 8) or recurrent breast cancer (n = 34) received regional chemotherapy (mitoxantrone 25 mg/m2 per 24 h) via the internal mammary artery or other vessels of the subclavian artery. To prevent artery thrombosis 500-1000 U heparin per hour were administered i.v. Tumour perfusion was monitored by intra-arterial angio-CT. Remission rates (CR + PR) were 100% (primary breast cancer) and 89% (recurrent tumours), respectively. Intra-arterial chemotherapy was well tolerated. No complications were noted. PMID- 8516441 TI - [Amelogenins: major extracellular matrix proteins regulating tooth enamel mineralization]. PMID- 8516442 TI - [Lipoprotein receptors]. PMID- 8516443 TI - [Molecular mechanism of transcriptional activation]. PMID- 8516444 TI - [Role of peroxisomes in lipid metabolism in animal cells; fibrates (hypolipidemic drugs)-caused alterations in lipid metabolism]. PMID- 8516445 TI - [Regulation of glucose transport by growth factors in mammalian cells]. PMID- 8516446 TI - [Current topics on eukaryotic mRNA transcription]. PMID- 8516447 TI - Digital subtraction angiography in the diagnosis of congenital heart diseases: analysis of 60 cases. AB - Ninety-one IVDSA and/or IADSA examinations with 192 injections were performed in 60 patients with congenital heart disease (CHD), including 31 anatomic anomalies. Axial projection was used in 23 patients. Analysis of the results of this series showed that accurate diagnosis by DSA confirmed by cardiac surgery together with definite diagnosis by DSA were obtained in 54 cases (90%). Two cases of nondiagnosis by DSA resulted from a suboptimal DSA method; four cases of partially accurate or mistaken diagnosis determined by cardiac surgery occurred because the axial view was not used and/or the anomalies were too small to be visualized by DSA. To increase the diagnostic accuracy of DSA in CHD, an optimal method of DSA must be selected according to the position of the anomaly and the hemodynamic data, and the axial view should be used to visualize the anomaly clearly in complex cases. In addition, DSA may fail to define a mild anomaly because of its lower spatial resolution. PMID- 8516448 TI - Famotidine for gastric radiography. AB - The effectiveness of famotidine (20 mg) in suppressing nocturnal gastric secretion during preparation for gastric radiography was studied in 243 patients. The gastric juice volume was calculated from a single upright radiograph of the stomach. The overall percentage suppression of nocturnal gastric secretion by famotidine was 60%, while it was 47% in patients with upper gastrointestinal symptoms. Radiological examinations were of diagnostic quality in 82% of the controls and 91% of the famotidine group; excellent film were obtained in 45% and 3%, respectively. Our findings suggest that famotidine could be a useful pretreatment for barium meal examinations. PMID- 8516450 TI - Portal-systemic encephalopathy: report of a case with unusual MR findings. AB - A case of subclinical portal-systemic encephalopathy with unusual MR findings is described. The basal ganglia and cerebral white matter were diffusely hyperintense on T1-weighted images. No similar cases have been previously described in the literature. PMID- 8516449 TI - Preoperative diagnosis of Meckel's diverticulum in a 62-year-old man: utility of an angiographic technique. AB - A 62-year-old man with severe anal bleeding was admitted to our ward as an emergency patient. Angiography of the superior mesenteric artery revealed an omphalomesenteric artery. Methylene blue was injected superselectively into the artery through an angiographic catheter at the time of subsequent laparotomy. Blood supply through the artery to the restricted area of the diverticulum could thus be defined in situ. PMID- 8516451 TI - MR imaging of seminal vesicle cysts associated with adult polycystic kidney disease. AB - An unusual case of seminal vesicle cysts associated with adult polycystic kidney disease (APKD) is presented. The magnetic resonance (MR) appearance of this rare entity has not been described before. A brief review of the literature is included and the role of MR imaging is discussed. PMID- 8516452 TI - Desmoplastic fibroma of bone. AB - We present a rare case of benign intraosseous desmoplastic fibroma, occurring in the tibial bone of a 48-year-old woman. The plain film features consist of a lytic, expansile lesion, in the metaphysis and epiphysis of the bone. We present a case involving the long bone in which the correct diagnosis was suggested by CT and MRI. The appearance of the lesion on CT and MR is described. PMID- 8516453 TI - Cavernous angioma of the middle fossa: a case report and characteristic MRI findings. AB - Cavernous angioma of the middle fossa is a rare lesion that is considered to originate from the cavernous sinus. Because of its profuse bleeding during surgery, it is crucial to make the correct diagnosis before an operation is performed. We report here a case of cavernous angioma occurring in the right middle fossa. MRI demonstrated an extracerebral mass extending from the middle cranial fossa into the cavernous sinus which showed low signal intensity on T1 weighted images and high signal intensity on T2-weighted images. Right carotid angiography demonstrated a faint vascular stain supplied by the meningohypophysial trunk. These findings suggested an extradural cavernous angioma originating from the cavernous sinus and extending into the middle-fossa. PMID- 8516454 TI - A stereotactic brain implant technique with high activity I-125 seeds using a conventional brachytherapy treatment planning system. AB - A stereotactic brain implant program with removable high-activity I-125 seeds has recently been implemented for the treatment of malignant brain tumors. A Brown Roberts-Wells (BRW) stereotactic frame with an NIH arc system and a guide template is used to introduce parallel catheters precisely into the tumor volume (Fig. 1). CT scans of patients with the BRW frame in place are used to determine the position of the catheters and the location of seeds in each catheter. The positions of the catheters are determined with respect to a "reference line" which represents the direction of approach in the central plane of the tumor. The seed coordinates are expressed in the catheter coordinate system with the X-axis along the catheter direction and the Y-Z plane parallel to the surface of the guide block. The Y-Z plane is orthogonal to x-axis. An AECL Theratronics Theraplane treatment planning system (SEED program) is used to obtain dose distributions based on seed coordinates. This treatment planning system does not require special purpose software for brachytherapy treatment planning. High activity I-125 seeds (nominal 10-15 mCi/seed) are after-loaded into the inner catheters of double coaxial silicone (Gutin) catheters according to a preplanned scheme. The physical aspects of the brain implant program, treatment planning technique, and radiation safety measures are described. PMID- 8516455 TI - Radiological-histological correlation of arterial changes in pancreatic carcinoma and chronic pancreatitis. AB - This study was intended to elucidate, on a histological basis, the origin of the angiographic abnormalities seen in three pancreatic carcinoma cases and three chronic pancreatitis cases. Irregular encasement and/or occlusion of the extrapancreatic large arteries were revealed to have resulted from serrated deformity and contraction of the arterial wall, which was surrounded by fibrosis and invasive carcinoma cells. Both of these changes in combination were characteristic in carcinoma cases, but the arterial walls never succumbed to tumor invasion. Arterial occlusions due to intimal thickening in the small arteries were morphologically similar in cases of carcinoma and chronic pancreatitis. PMID- 8516456 TI - [The language to describe fractures]. PMID- 8516457 TI - [Imaging of the cervico-maxillo-facial emergencies]. PMID- 8516458 TI - [Dynamic vascular imaging with magnetic resonance imaging of the thoracic and abdominal region. Technique optimization]. AB - Several Magnetic Resonance (MR) imaging techniques for the study of the main thoracic and abdominal vessels are analyzed. Such techniques based on the static representation of vessels, as MR angiography (MRA), are considered, together with dynamic techniques--i.e., cine MR--and those based on ultra-fast sequences with bolus contrast medium administration; the latter are considered also according to their use in the study of the early parenchymogram. Namely, the investigated techniques are: 3D/2D inflow imaging with and without presaturation, 3D inflow imaging with paramagnetic contrast medium administration, 2D/3D phase/dephase subtraction imaging, cine MR with heart gating, the sequential dynamic single slice technique with bolus contrast medium, and the apnea multi-slice imaging. The main parameters are indicated for each technique and type of sequence. From our experience, rather precise indications emerge as to the use of the various techniques according to the investigated region and to the suspected disease. The best techniques for demonstrating sacciform aneurysms proved to be the 3D inflow ones, as well as the cine MR and the turbo-flash sequences with contrast medium; as for dissecting aneurysms, cine MR proved best. In portal flow conditions and in major veins thromboses, 2D inflow and phase/dephase subtraction sequences are suggested. In the study of renal stenoses, limitations and advantages of 2D versus 3D sequences are compared. Moreover, indications, limitations and specificity are analyzed of the early parenchymogram based on ultra-fast sequences with paramagnetic contrast medium. In the authors' experience, the different MR vascular imaging techniques must be considered only an integration to more specific investigations, but it is likely that, as it happened with MRA of the head and neck, the increase in resolution and the reduction in artifacts will--soon--turn this kind of imaging into the examination of choice in vascular studies. PMID- 8516459 TI - [Dynamic sequential study of hepatic nodular lesions with ultra-fast sequences and fast bolus of gadolinium-DTPA]. AB - Eighty-five patients with single/multiple nodular hepatic lesions (10 focal nodular hyperplasias, 37 liver hemangiomas, 24 metastases and 16 hepatocellular carcinomas; 2 patients had associated lesions) were examined with dynamic single slice sequences and fast i.v. bolus injection of Gd-DTPA. The dynamic single slice technique was used to evaluate the peculiar features of the dynamic enhancement. The snapshot sequence proved best to provide the high temporal resolution of the dynamic parenchymal enhancement (scanning time < 1 second, one frame every third second). The following variables were investigated: nodular lesion intensity in the first basal snapshot image, enhancement appearance and its contemporaneity with arterial, venous or portal flows, enhancement gradient relative to surrounding liver parenchyma, morphologic features of the enhancement and its centrifugal/centripetal patterns. The enhancement curve of focal nodular hyperplasia increased very quickly during the first 20-25 seconds. This enhancement was quite similar to the arterial one and always occurred before portal and systemic venous times. Hemangiomas exhibited a typically slow growth curve in the first 120 seconds, with a positive final gradient value relative to liver parenchyma. The appearance of peripheral contrast enhancement was a typical sign after 30 seconds. Metastases exhibited similar dynamic enhancement to hemangiomas, but peripheral enhancement was never observed and, after 120 seconds, gradient was null or negative relative to the adjacent liver parenchyma. Moreover, enhancement always followed portal times. Hepatocellular carcinomas showed an early growth curve, preceding portal times, but less marked than in hyperplasia. The study of our series provided the preliminary semiology of early dynamic enhancement patterns, which is quite specific to recognize and differentiate nodular hepatic lesions. PMID- 8516460 TI - [2D TOF angio-MR of the thoraco-abdominal aorta. Technique and clinical applications]. AB - The diagnostic role of Magnetic Resonance Angiography (MRA) was investigated in the study of the thoracic and abdominal aorta. Thirty-two patients with different conditions were examined: the thoracic aorta was affected in 7 cases (3 aneurysms, 2 dissections, 2 tumors) and the abdominal aorta in 25 cases (21 aneurysms, 3 stenoses and 1 dissection). Moreover, 2 kinkings and 1 dextroposition of the thoracic aorta were observed as occasional findings, together with 15 abdominal aorta kinking cases. A 1.5-T superconductive magnet (Magnetom, Siemens) with circular polarization body coil and the 2D TOF (FL 18 degrees, TR 30 ms, TE 10 ms, ST 5 mm, 1-mm overlap) technique were used. The images acquired on the coronal and sagittal or parasagittal planes were rotated from -45 degrees to 45 degrees and from 60 degrees to 120 degrees during post processing, according to MIP. Digital angiography was the gold standard in all cases, angiography and CT were the gold standards for aneurysms, and surgery for the lesions reaching the thoracic aorta. The 2D TOF technique allowed excellent visualization of both the thoracic and the abdominal aorta. In thoracic aorta conditions, MRA always identified aneurysms and assessed their relationship to epiaortic branchings. Moreover, MRA identified 2 cases of thoracic aorta dissection. In one case (1/2) MRA failed to depict aortic wall infiltration by tumor. In 21 abdominal aorta aneurysms, MRA always correctly demonstrated both the extent of the aneurysm and its relationships to renal and iliac arteries. Moreover, the thrombotic aneurysmal component was demonstrated, together with left renal vein course, which was retroaortic in 4 cases. Abnormal course, stenoses (2 cases) and dissection of the abdominal aorta were always identified by MRA. PMID- 8516461 TI - [Comparative evaluation of the SPIR sequence with gadolinium and other sequences in bone diseases]. AB - In order to assess the value of the SPIR (Spectral Presaturation with Inversion Recovery) sequence (a fat-suppression technique) with Gd-DTPA in the investigation of skeletal diseases, 50 patients were examined with conventional SE T1- and T2-weighted sequences, as well as with SE T1 and SPIR sequences after the i.v. injection of Gd-DTPA. Twenty patients were affected with a skeletal infection (11 spondylodiscites and 9 osteomyelitis) and 5 with a primary tumor; 15 had metastases and 10 a hemolymphopoietic disorder (6 myelomas and 4 non Hodgkin's lymphomas). In the four groups of patients, the mean visibility of skeletal lesions was higher on SPIR images with Gd-DTPA than on the other images, even though a statistically significant difference was observed only in the group of infections (p < 0.002) and in myelomas and lymphomas (p < 0.001). In 13 cases with extraosseous spread, visibility was higher on contrast-SPIR images than on the other sequences, even though high sensitivity was also exhibited by SE T2 weighted sequences. Even though the SPIR sequence still exhibits some technical limitations, our study assesses the value of this sequences with Gd-DTPA in the investigation of skeletal lesions. The major advantages of contrast-SPIR imaging follow: 1) it shows skeletal lesions, which are isointense on enhanced SE T1 weighted images, 2) it provides better visibility of the lesion than the other sequences, more accurately defining their borders, 3) it provides better anatomical detailing than SE T2-weighted images and 4) its sensitivity is higher. PMID- 8516462 TI - [Intra-osseus hidden fractures of the knee in athletes: assessment with magnetic resonance imaging]. AB - The diagnostic capabilities of Magnetic Resonance Imaging (MRI) were investigated in the study of occult intraosseous fractures of the knees in athletes; this pathologic condition is difficult to assess with conventional diagnostic techniques. Twelve athletes were considered and submitted to MR examinations 1-8 days after trauma. All patients had undergone plain films, 6 of them CT and 3 scintigraphy. Four patients were followed with MRI at 15 and 30 days. Plain films were negative in all patients. On CT, in one case only an area of segmental osteoporosis was identified at the anterolateral tibial plateau. Scintigraphy provided positive but aspecific results in all three patients. MRI demonstrated all lesions: 3 at the tibial plateau, 5 at the lateral femoral condyle and 2 at the medial femoral condyle. Double localizations were observed in two patients, femorotibial and tibiopatellar, respectively. In no case lesions of meniscal and/or capsuloligamentous structures of the knee were associated. Arthroscopy, which was employed in two patients, confirmed MR diagnosis. Thanks to its high spatial and contrast resolution and to its multiplanar capabilities, MRI can be considered the method of choice in the study of occult intraosseous fractures of athletes' knees. Beside localizing the lesion site, MRI allows the evaluation of its extent (linear or reticulo-geographic patterns) and the exclusion of possible involvement of meniscal and/or capsulo-ligamentous structures. MRI follow-up of this condition showed the "restitutio ad integrum" of the medullary trabecular bone as early as at 15 and 30 days, depending on lesion pattern and extent. On the basis of our experience, MRI emerges as the only diagnostic technique allowing the accurate evaluation of occult intraosseous fractures of the knee in athletes, because it provides early and detailed information which is valuable for the therapeutic approach, which is of fundamental importance to resume sports activity quickly. PMID- 8516463 TI - [Computed tomography demonstration++ of calcaneal morphotypes in plantar arch abnormalities]. AB - CT and MR investigations of the foot generally follow clinics, to confirm the presence of pathologic changes. Plantar arch alterations, which predispose to pain in overload, are not included and thus CT and MR examinations are not usually performed because the patient is not standing. A series of 80 patients (49 males and 31 females, age range: 8-74 years old) was divided according to the presence of clinical signs of plantar arch alterations. Plantar and coronal CT scans were performed according to strict protocols. On plantar scans some patterns were identified, corresponding to the typical signs of conventional radiographs, which are suggestive of flat, cavus and normal feet. On coronal bimalleolar scans, other heel patterns were detected, which are suggestive of medial-concave, varus and orthogonal feet. In our opinion, the above patterns are an example of heel adaptation to plantar arch variability. Especially in the patients with flat feet, the calcaneus-cuboid-metatarsal angle was almost 180 degrees on plantar scans; high agreement was observed, on coronal slices, with the medial-concave heel pattern. The varus morphotype was very frequent among the patients with cavus foot on coronal slices; on plantar scans it corresponded to a calcaneus-cuboid-metatarsal angle (< 180 degrees). CT signs must be accurately described for they help interpret pain related to foot architecture, especially in the patients in whom the possible relationship between symptoms and plantar arch alterations was underestimated. PMID- 8516464 TI - [Digital cephalometric teleradiography with storage phosphors. Comparative study]. AB - Digital cephalometric radiography with light-emitting phosphors was performed on 15 patients during an orthodontic survey. Lateral views were performed; digital post-processing was carried out according to 3 different sets of characteristic variables (analogic-like, Xeroradiography-like and custom-made). Comparative cephalometric film radiographs were performed on another group of 15 patients matched for age and clinical problems. All the digital and conventional images were evaluated by 3 independent observers, who scored 0-2 the visibility of 16 cephalometric landmarks. Digital cephalometric radiography always provided good and clear images, which were easy to read by every observer, thanks to contrast optimization in the digital technique and to the possibility of interactive post processing that could improve the lowest-quality images. The visibility study of 16 cephalometric landmarks resulted in a moderately higher score for film cephalography than for the digital technique (79.6/96 versus 78.1/96). Among digital post-processing variables, the customized curve gave the best results (mean score: 78.8/96). Digital cephalometric radiography allowed marked reduction in radiation dose (approximately 30-40% of conventional radiographs). This is a major factor when considering the widespread use of this technique and the young age of most patients. PMID- 8516465 TI - [Role of integrated imaging (computerized tomography and echography) in the surgical reconstruction of the external ear]. AB - Three-dimensional Computed Tomography (3DCT) imaging methods of the skull and ribs by axial and contiguous slices allow the selective rendering of the involved structures. The possibilities given by variable threshold ranges allow 12-bit density structures (Hounsfield Units) to be obtained within threshold limits. Imaging has been optimized by shading solids. Such methods, together with US (duplex-Doppler) techniques, offer new diagnostic possibilities relative to the treatment planning of patients with either congenital malformations or acquired abnormalities of the external ear and in the evaluation of associated abnormalities of craniofacial areas. In the reconstruction of the earlap by autograft of modelled rib cartilage, after preparing an expanded otomastoid skin flap, the above methods allowed accurate preoperative planning with consequently significant reduction of surgical time and better clinical results. Six patients with earlap abnormalities (four with microtia due to complete hemifacial microsomia syndrome, one with anotia and one with post-traumatic loss of the earlap) were studied for reconstruction. High-quality 3DCT images of the rib and auricolar cartilage were obtained in real-scale representation (1:1 ratio) the evaluation of the donor site and of the autograft size. Useful pieces of information on the development and vascularization of an expanded otomastoid flap, after gradual and constant expansion, were given by duplex-Doppler US, which allowed easy monitoring in both surgical planning and follow-up. PMID- 8516466 TI - [Role of computed tomography in the follow-up of patients treated with radical surgery and reconstruction with myocutaneous flap for head and neck tumors in advanced stage]. AB - January 1988 to April 1992, 26 patients with advanced head and neck carcinoma underwent head and neck reconstructive surgery with pectoralis major myocutaneous flap (PM-MCF). Over the same period, all cases were submitted to CT to assess the value of this technique in the follow-up. Fourteen patients relapsed (54%). Of them, 5 (36%) were positive on both clinical examination and CT; 8 cases (57%) exhibited evidence of disease on CT only and in 1 patient (7%) CT was negative and the recurrence appeared as a fistula on follow-up exams. CT was of great value in the management of the patients with advanced head and neck carcinoma treated with reconstructive surgery with PM-MCF. However, CT findings must be carefully interpreted because postoperative and postirradiation complications or anatomic alterations may mimic tumor recurrences. PMID- 8516467 TI - [Unknown primary bone metastasis: therapeutic and diagnostic strategies]. AB - The primary site remains unknown in 0.5-15% of patients with multiple metastases. In 5-20% of these patients bone metastases are the first sign of disease. Survival after diagnosis ranges 2 to 6 months and 1-year survival is less than 25%. First of all, this paper reviews the current diagnostic and therapeutic approaches to patients with bone metastases from an unknown primary site and then reports the 10-year experience with radiotherapy at the Radiotherapy Division of the Centro di Riferimento Oncologico (Aviano) and of the Pordenone General Hospital in this patient population. Seventy-nine patients with bone metastases were evaluated. In 33 patients histology confirmed the original diagnosis and in 46 patients diagnosis was based on radiological and clinical findings. With respect to pain relief, differences in irradiated areas and in the ages of the patients were not significant. The patient's sex, however, did make a difference both to the degree of pain relief achieved and to survival (more favorable in women). To conclude, this paper suggests the diagnostic procedures necessary for the correct follow-up of patients with bone metastases from an unknown primary site. PMID- 8516468 TI - [Mycoplasma pneumoniae pneumonia. Can radiologic features suggest the etiologic agent?]. AB - The present study was aimed at evaluating whether Mycoplasma pneumoniae (MP) pneumonia presents with typical X-ray patterns which can help its diagnosis. The chest films of 32 adult patients with serologically proven MP infections were reviewed. Confluent or patchy consolidation was the most common finding (66% of patients), interstitial involvement was much less frequent (19%), and so were "mixed" patterns (15%). Unilateral involvement was common (69%), the lower lobes were frequently involved (52%) and in 78% of cases only one lobe was affected. Pleural fluid (40%) and atelectasis (31%) were commonly seen, while hilar adenopathy was rare (9%). In substantial agreement with previous studies, no distinctive X-ray pattern of MP pneumonia was found and marked differences were seen to exist in its radiographic appearance. Despite these obstacles, some characteristic X-ray findings were suggestive of MP pneumonia: diffuse/localized interstitial involvement appeared to be the most helpful sign, in combination with clinical and epidemiologic data. On the contrary, patchy and acinar consolidations are slightly suggestive of MP etiology. PMID- 8516469 TI - [Quantitative evaluation of blood in vivo with computed tomography]. AB - A positive correlation between the attenuation values of blood in vitro and hemoglobin concentration has been described by other authors. Our study is aimed at: 1) investigating the influence of artifacts on the measurement of blood density in vivo, 2) verifying the possible correlation between blood values and Hounsfield's units (HU) in vivo, 3) assessing whether such a correlation may be useful in calculating hemoglobin concentration, 4) investigating whether a significant difference in blood density exists between normal and anemic subjects, and 5) investigating the eventual borderline density values which separate the two populations. Fifty adult patients underwent CT of the upper abdomen for several clinical reasons. Twenty-six males, mean age 63 +/- 15 SD, and 24 females, mean age 63 +/- 14 SD, were included in our series. The two groups were then subdivided into two additional groups including anemic and normal subjects -14 g/dl and 12 g/dl being taken as the borderline values for males and females, respectively. Blood density was measured after defining two regions of interest (ROI) on the aorta and inferior vena cava. The results show that: 1) there are few image artifacts, which are sometimes detected only because of different numbers in aorta and vena cava; for quantitative blood measurement, 4 HU was considered as an acceptable difference; 2) the correlation between HU and hemoglobin concentration which was found in vitro was also seen in vivo (r = 0.76, p < 0.001). Furthermore, high positive correlation was observed between attenuation values and red cell count (r = 0.68) or hematocrit (r = 0.75). 3) However, this correlation cannot be used to calculate the patients's blood count since HU dispersion relative to the regression line is too high. The straight line of regressed computation, reporting the density values on the abscissa axis, shows a b = 0.33 slope and the intersection point is a = -1.43, SE b = 0.04, SE a = 1.76 and SE estimate = 1.56. When the mean density value was 43 HU in our sample, the expected hemoglobin value was 12.76 g/dl (+/- 1.58 SD). 4) Nonetheless, a significant difference in blood attenuation values was seen between normal subjects and anemic patients (p < 0.001). 5) This difference identifies a borderline density value, below which the patient is sure to be anemic (99% confidence), but nothing else can be said on the patient's normality: the value is 33 HU for females and 36 HU for males. These values allowed 20% of anemic subjects to be correctly identified, versus 5% of the same group detected with diagnosis images. PMID- 8516470 TI - [Abnormalities of the hepatic artery++ in relation to portal hypertension surgery. Study with angiography and echography]. AB - This study was aimed at investigating the occurrence of hepatic artery variants, at comparing the diagnostic value of duplex Doppler US with that of angiography, and at correlating the results with the technical problems in portal hypertension surgery. All patients were studied with angiography, conventional and duplex Doppler US. In 162 patients with portal hypertension, 38 hepatic artery variants (23.4%) were observed and classified according to Michaels. The commonest variant recognized by angiography was right hepatic artery arising from superior mesenteric artery (type III according to Michaels). US demonstrated hepatic artery variants in 9/162 patients (5.5%). At surgery, variants were found in 3/162 subjects (1.8%) and caused surgical problems in 2 of them (1.2%) - i.e., right hepatic artery arising from superior mesenteric artery. Arteriography is still the best examination to depict hepatic artery variants, while duplex Doppler US demonstrates only a few types. Moreover, the number of variants detected by imaging techniques (23.4%) differs greatly from that observed at surgery (1.8%). Finally, hepatic artery variants are not correlated with surgical problems, nor can the latter be foreseen by imaging methods. US is useful but not essential to detect hepatic artery variants which are subsequently confirmed by angiography. PMID- 8516471 TI - [Direct radiographic enlargement in mammography in everyday practice. Indications and limitations]. AB - One thousand mammograms of non-preselected patients were reviewed in order to assess in how many and which cases an equivocal diagnosis can be made unquestionable and to test the value of follow-up exams with direct radiographic magnification. Direct radiographic magnification was used in all questionable cases (3%): 18 lesions were characterized by microcalcifications and 12 by nodules. Four cases were diagnosed as unquestionable (13%)-1 microcalcification and 3 nodules-while 13 patients were reexamined with mammography only. Even though the percentage variation from equivocal to unquestionable diagnoses is modest but significant, direct radiographic magnification is always useful in the follow-up. PMID- 8516472 TI - [Development of a teleradiology system]. AB - PURPOSE: the development of a cost-effective diagnostic system for transmitting high-resolution images on normal phone lines. MATERIALS AND METHODS: A 486 PC with super VGA screen, 16,800-band external modem and graphic software. RESULTS: the graphic software allows the PC to be connected to the video output of MRI, CT or US units, or to a video camera as in the case of X-ray units. Image spatial resolution is as high as 1,024 x 768 lines. Transmission times are lower than 45 seconds, corresponding to files of 50-80 kbytes. In 6 months, more than 130 Megabytes (500 images) were transmitted between our diagnostic center and our consultants in northern Italy, France and California. CONCLUSIONS: this cost effective teleradiology system allows real-time image transmissions between diagnostic centers all over the world for scientific updating and quick reference purposes. Portable units can be developed. PMID- 8516473 TI - [Assisted reporting: preliminary evaluation of the effectiveness of the management of a Thoracic Radiology Unit]. AB - Conventional chest radiographs correspond to 50% of the normal workload of a diagnostic radiology department and account for the lengthening of reporting times, thus affecting the profit of a general hospital deeply. The authors describe a software specifically applied to the reporting of chest X-rays which allows "macro" reports for typical or negative findings and which makes reports by sequential questions for more complex conditions. Its value was investigated based on nearly two years' uninterrupted working experience. During four month 7175 examinations were performed: 6480 (90.3%) in the diagnostic room, plus 685 (9.5%) bedside and emergency exams. Computer-assisted reports amounted to 95% of the total figure in the first group and to 46% in the second one. The results follow: 1) waiting times were substantially reduced; 2) administrative workload was markedly decreased; 3) less expert medical staff greatly benefitted from an efficient didactic and learning activity. Thus, good results were obtained, especially relative to the possibility to obtained actual real-time reports of chest radiographs with no loss in diagnostic accuracy. PMID- 8516474 TI - [Results of the use of the Strecker and Palmaz stents in the iliac artery region. Two years' experience]. AB - Our personal experience is reported with the use of vascular endoprostheses (Strecker and Palmaz stents) in the non-surgical treatment of iliacofemoral steno occlusive arteriopathy. Over a 15-month period, 56 PTAs were performed in 40 patients; 20 vascular endoprostheses were positioned--17 Strecker and 3 Palmaz stents--in 16 patients, to correct such PTA complications as dissections or to improve the results of a suboptimal PTA maneuver. Venous DSA follow-up was performed at 30 days, and serial color-Doppler US studies were performed every fourth month. Immediate and satisfying clinical results were observed in 15/16 patients (93.7%): only one case of acute thrombosis following the procedure was observed, which could not be treated with intraarterial fibrinolytic therapy and was therefore operated on. Overall long-term patency rate is 100%, mean follow-up is 13.8 months. Finally, the indications for the use of such devices in iliacofemoral arteriopathies are critically discussed, together with the criteria of choice of a type of stent over another one, the immediate and long-term results and the best follow-up protocols. PMID- 8516476 TI - Information on radiation hazard and on radiological protection in medical school in Italy. AB - The state of teaching Radiation Protection in Medical School in Italy was considered. An historical approach was utilized, in order to define periods of time characterized by different conditions. Some data are collected by a concise enquiry on the information given during the course of Radiology in the second triennal cycle, and on some other teaching courses including information on radiation effects. The conclusion is that teaching times are exceedingly reduced, and the need of improving the diffusion of knowledge in the field is stressed. An official Act of the OECD and of European Community is expected, with the aim of emphasizing the importance of the information of doctors on Radiation protection as a problem of public interest. A proposal is advanced of implementing the Teaching of Radiobiology in the second triennal cycle, changing the name of the course in "Radiobiology and Radiological Protection". PMID- 8516475 TI - [Treatment of Plummer's adenoma: correlation between ultrasonography-guided percutaneous injection of ethanol and autoimmunity]. AB - The authors investigated the value of percutaneous ethanol injection in the treatment of Plummer's adenoma. Ten patients were studied: they exhibited a single, hot and toxic nodule in the thyroid. Thyroid autoimmunization (TSAb; TMAb; TGAb) and function (T3; T4; TSH; FT3; FT4) were studied in all patients, before treatment and at 1 month and 3 months. Scintigraphy with 99Tc was performed at the same time intervals. In the euthyroid stage, alcoholization was preceded by US and cytology. Three-four ml of ethanol 95 degrees were injected once or twice a week, from a minimum of 3 to a maximum of 8 injections. Treatment was successful in 2 cases; partial success was obtained in 4 cases, and in 4 cases treatment failed. In all successful cases antibodies were negative and the nodules had hypoechoic echostructure, with a peripheral hypoechoic halo and no areas of internal colliquation. Thus, US-guided percutaneous alcoholization seems to be capable of correct indications in hypoechoic nodules not exhibiting areas of colliquative necrosis and with negative antibodies. However, the problem of the dose of alcohol to inject to treat the nodule thoroughly is still to be debated. PMID- 8516477 TI - [Exclusive radiotherapy of pyriform sinus carcinomas. Retrospective analysis of 90 cases]. AB - In the present study 90 patients affected with pyriform sinus carcinomas are analyzed. They underwent irradiation alone from 1970 to 1986. All cases were staged according to TNM criteria (UICC 1982): 7 were T1, 16 T2, 40 T3, 27 T4, 36 N0, 18 N1, 3 N2, 33 N3. Radiotherapy was performed with 60Co. In all cases doses of 60-70 Gy were delivered to T and N1 and doses of 45-50 Gy to N0. Locoregional control obtained in 35 patients (38.9%): 6/7 T1 (85.7%), 9/16 T2 (56.2%), 15/40 T3 (37.5%), 5/27 T4 (18.5%) and 20/36 N0, 8/18 N1, 1/3 N2, 6/33 N3. The overall and NED 3-year survival rates are 23.3% (21/90) and 20.0% (18/90), respectively; at 5 and 10 years all patients alive are NED, with survival rates of 12.2% (11/90) and 9.8% (5/51) respectively. Locoregional failures were observed in 12/35 cases (34.3%); 91% of them occurred within the first two years of follow up (mean: 10 months). Distant metastases appeared in 26/90 patients (28.9%) and secondary tumors occurred in 10/90 cases (11.1%). Our experience confirms radiotherapy to be an effective alternative treatment to surgery in the early stages (I-II) of pyriform sinus carcinomas, but no more than only a palliative treatment in stage III-IV cancers. PMID- 8516478 TI - [Actinomycosis of the sacrococcygeal region with spinal cord involvement]. PMID- 8516479 TI - [Imaging diagnosis in the prenatal diagnosis of sirenomelia]. PMID- 8516480 TI - [Leiomyoma of a dorsal vein of the foot. Clinico-radiologic case]. PMID- 8516481 TI - [Congenital arteriovenous malformation of the leg diagnosed with Doppler echography]. PMID- 8516482 TI - [Mammographic diagnosis of foreign bodies left after surgery. Report of 2 cases]. PMID- 8516483 TI - [Monolateral pseudotumor mammographic appearance of fibrous dysplasia. Report of 3 cases]. PMID- 8516484 TI - [Computed tomography features of peritoneal malignant mesothelioma. Presentation of 2 cases]. PMID- 8516485 TI - Cellular immunity in interstitial nephropathy. AB - Inflammatory tubulointerstitial nephritis (TIN), either as a primary or as a secondary event, plays an essential role in the development of all forms of chronic renal failure. Experimental models of TIN should help in understanding TIN in humans. As in experimental glomerulopathies, the target antigen can be a kidney structural antigen, from the tubular basement membrane (TBM) or not, or a foreign antigen. While some models are due to deposits of free antibodies or circulating immune complexes, many others involve cell-mediated immunity. This last aspect explains the importance and the originality of experimental TIN. PMID- 8516486 TI - Red blood cell Li+/Na+ exchange in patients with diabetic nephropathy and essential hypertension: therapeutic implications. AB - Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+ countertransport (CT). Li+/Na+ CT is a membrane function which exchanges intracellular Li for extracellular Na in vitro. High Li+/Na+ CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mitogens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+ CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+ CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+ CT is often associated with hyperlipidemia, hyperuricemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/Na CT are at risk of early renal and cardiac impairment. PMID- 8516487 TI - Blood pressure control effects on the progression of chronic renal failure. PMID- 8516488 TI - Mechanisms of glomerular injury: overview and relation with hemostasis. AB - The mechanisms of glomerular injury can be separated into nonimmunologically mediated glomerulonephritis (GN) such as diabetes, leading to glomerular hypertension and into immunologically mediated GN. The immunologically mediated GN may induce chronic glomerulopathy such as membranous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In inflammatory GN, most of the mediators could be synthesized either by infiltrating cells or by resident glomerular cells. They include cytokines, lymphokines, complement activation, generation of superoxyde anions, arachidonic acid metabolites, and fibrin deposition. (a) We have investigated the interaction between isolated glomeruli and platelets and have demonstrated that lipidic and proteic extracts of glomeruli enhance thromboxane B2 platelet synthesis. This fact is related to the generation by isolated glomeruli of saturated fatty acids and tissue factor. (b) We investigated the interaction between rat isolated glomeruli and peritoneal macrophages. We have demonstrated that 12-HETE synthesized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis. (c) We have demonstrated, using human glomerular epithelial cells, that alpha-thrombin, the active form of thrombin, generated before fibrin formation, is able to induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are complex, certainly acting by multiple pathways. So far, the mediators leading to proteinuria and renal failure after glomerular injury remain under investigation. PMID- 8516489 TI - Dialysis-associated amyloidosis. AB - Dialysis arthropathy (DA) and carpal tunnel syndrome are debilitating complications caused by dialysis-associated amyloidosis. They arise after several years of hemodialysis with cuprophane and their onset can be delayed with the use of high-flux dialysis. Serum C-reactive protein is elevated in patients with dialysis arthropathy, indicative of inflammatory processes. X-rays show periarticular bone cysts and erosive spondyloarthropathy. High-flux dialysis improves DA, but transplantation remains the best treatment. PMID- 8516490 TI - Calcium antagonists and renal protection. AB - A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view. PMID- 8516491 TI - Antihypertensive effect of nitrendipine in the hypertensive patient with renal impairment. AB - Calcium antagonists exert several characteristic effects on the kidney that potentiate their antihypertensive effect. The objective of the present study was to investigate the effectiveness of nitrendipine in the presence of different degrees of renal impairment. Two groups of hypertensive patients were included in the study. Group 1:10 patients with arterial hypertension secondary to chronic renal parenchymatous disease and adequately controlled with a diuretic and/or a beta-blocker who were switched to nitrendipine. These patients were then followed monthly for 1 year. Group 2:24 patients diagnosed as having essential hypertension who presented values of urinary albumin excretion above 30 mg/day after a minimum of 3 years of adequate blood pressure control with a diuretic and/or a beta-blocker. Patients were randomly assigned to continue with the same therapy or to switch to nitrendipine for 1 year. In both groups nitrendipine was as efficacious as standard therapy for controlling blood pressure and did not induce changes in renal hemodynamics. Nitrendipine did not modify the level of proteinuria in group 1, nor the urinary excretion of albumin in group 2. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension and different degrees of renal function impairment. PMID- 8516492 TI - Application of monoclonal anti-idiotypes in the study of AL amyloidosis: therapeutic implications. AB - A monoclonal anti-idiotyped antibody (IgG1k MAb 3B11D4) has been raised against the lambda-chain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylated lambda-chain monomers, nor the 15- to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of the lambda chain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion. PMID- 8516493 TI - Hypertension and renal disease. AB - Chronic renal parenchymal disease is the most common cause of secondary hypertension: By the time end-stage renal disease develops, its prevalence approaches 75-85%. It was previously believed that hypertension caused arteriolar nephrosclerosis and ischemic renal injury superimposed on primary renal parenchymal disease, contributing to progressive renal insufficiency. Recently, the importance of an increased intraglomerular hydraulic pressure due to loss of renal autoregulation has been emphasized. There are several potential explanations concerning clinical studies which have not uniformly demonstrated slowing of progressive renal damage with antihypertensive therapy: Random BP measurements may not adequately reflect average BP levels, or, alternatively, the widely accepted target level of BP control may be inadequate. In a retrospective study, we found that hypertensive nephropathics had higher serum creatinine levels than normotensives; in another prospective trial we have demonstrated that enalapril is an effective antihypertensive agent in patients with IgA nephropathy, and it also ameliorates the evolution of the disease. PMID- 8516494 TI - Familial Mediterranean fever-associated amyloidosis. PMID- 8516495 TI - Glomerular sclerosis: from rat to man. PMID- 8516496 TI - Serum cholesterol falls spontaneously in nephrotic patients with progressive renal disease. AB - Total cholesterol (TC) levels were lower than expected in some patients with advanced renal disease and nephrotic-range proteinuria. Studies of 35 clinically stable nonuremic patients and of 12 nephrotic patients with advancing renal failure were therefore performed. Analysis of pooled biochemical data from 35 patients who were hypercholesterolemic on entry to the clinic revealed a positive correlation between TC and reciprocal creatinine (l/Cr) while serum albumin (ALB) was negatively correlated with l/Cr and TC. In the 12 nephrotic patients with negative reciprocal creatinine slopes there was a strong correlation between the slopes of l/Cr and TC. These data suggest that plasma cholesterol falls in the nephrotic hypercholesterolemic patients in whom renal disease progresses, and that the slopes of plasma cholesterol and reciprocal creatinine are closely related. PMID- 8516497 TI - Therapy of amyloid diseases. AB - Deposition of amyloid in the organism can lead to severe clinical symptoms and syndromes which are referred to as amyloidosis. However, amyloidosis is not a pathogenetically single disease entity. Various amyloid diseases are known which can clearly be distinguished by identifying the protein from which the amyloid is derived. Since the amyloid syndromes are pathogenetically diverse, each of the different amyloid diseases needs to be treated differently, and a type-specific amyloid therapy is mandatory. Unfortunately, an efficient therapy is not yet available for most amyloid syndromes. It is the purpose of this review to show how the different amyloid syndromes are distinguished definitively from each other and what has been successful in the effort to establish an efficient therapy of the various amyloid deposits and different amyloidoses. PMID- 8516498 TI - Immunotactoid glomerulopathy (ITGP): a not fully defined clinicopathologic entity. AB - Immunotactoid glomerulopathy is characterized by the ultrastructural finding of fibrillary or microtubular deposits in patients without systemic diseases such as SLE, diabetes, paraproteinemias, cryoglobulinemia, or amyloidosis. These deposits correspond in most (but not all) cases to immunoglobulin and complement deposits as shown by immunohistochemical techniques. Different light microscopic patterns (mesangioproliferative, membranous, membranoproliferative, and crescentic) have been reported. Clinical presenting feature is characterized by proteinuria (often of nephrotic range), hematuria, and hypertension in most cases. Chronic renal failure requiring hemodialysis or transplantation is described in more than half the patients. Pathogenesis has not yet been elucidated and only some speculative hypotheses have so far been suggested. At present there is no clear evidence that we are dealing with a new pathologic entity, but larger series must be collected and studied in order to find a correct taxonomic collocation of this glomerulopathy. PMID- 8516499 TI - Controlled trials on low-protein diet: effects on chronic renal insufficiency progression. AB - The effect of a low-protein diet (LPD) on chronic renal insufficiency (CRI) progression was investigated by reviewing the published studies. Only three of these fulfilled the main methodological criteria of being randomized, prospective, and controlled: those of Rosman, Ihle and Locatelli. These trials involved 811 patients (671 evaluated: 338 on a LPD, 333 as controls) and had a mean follow-up of 29 months (range 18-48), for an estimated total of about 17,335 patient-months. The only trial whose results showed that LPD had a positive effect on chronic renal failure (CRF) progression was Ihle's study, with the lowest weight (6.7%) and involving the most severe CRF; effects limited to the patients with more advanced CRF were found in the Rosman study, with an intermediate weight (41.8%); and little effect, if any, was found in the Locatelli trial, accounting for 51.5% of patient-months, with less severe CRI. In conclusion, analysis of published randomized, prospective, and controlled trials offers little or no support for the hypothesis that a LPD has a clinically significant effect on the early CRI progression, although a very low protein diet seems to postpone the need for dialysis. PMID- 8516500 TI - Unilateral nephrectomy and progression of renal failure. AB - Extensive ablation of renal mass in experimental animals leads to progressive glomerulosclerosis and chronic renal failure (CRF). Clinical studies are far from answering the question whether patients with reduced renal mass are at risk of developing progressive CRF. The aim of our study was to examine the morphological and functional aspects of the remnant kidney in a group of patients who underwent unilateral nephrectomy for renal tuberculosis: 313 patients (161 M, 152 F) mean age 57.2 +/- 10.7, were examined after a period ranging from 13.56 to 591.2 months. All patients were on ad libitum diet. Hypertension was found in 34.19% of the patients; SBP was 155.29 +/- 19.9 mmHg and DBP was 92.74 +/- 13.07 mmHg. Estimation of renal size performed by ultrasound scanner gave the following results: length 116.78 +/- 8.99 mm; width 58.24 +/- 7.21 mm; thickness 17.88 +/- 1.96 mm. Kidney function assessed by serum creatinine levels showed a mean level of 1.28 +/- 0.53 mg%. Forty-two patients (13.41%) had serum levels > 1.5 mg% but 18 of them had nonconcomitant systemic or renal involvement. Microalbuminuria determined by RIA assay was found in 50.5% of the patients. In our group of patients renal functional impairment was low and hyperfiltration expressed as microalbuminuria does not appear to be a primary factor in the progression of renal failure. PMID- 8516501 TI - Structural causes of cardiac dysfunction in uremia. AB - While coronary heart disease is undoubtedly a major cause of cardiac morbidity and mortality in uremia, important noncoronary problems contribute to the common presence of cardiac problems. Based on clinical and experimental studies, we could show: (i) Left ventricular hypertrophy (LVH) can be dissociated, at least in part, from elevation of blood pressure. (ii) In uremia, PTH-dependent intermyocardiocytic fibrosis occurs; it may account, at least in part, for disturbed LV compliance and contribute to the arrhythmogenic potential. (iii) Blood pressure-independent abnormalities of intracardiac arterioles and reduced myocardial capillary supply are observed. PMID- 8516502 TI - Primary (AL) amyloidosis. PMID- 8516503 TI - Diagnostic criteria of analgesic nephropathy in patients with end-stage renal failure. PMID- 8516504 TI - [Microalbuminuria: predictive factor of renal and cardiovascular risk]. PMID- 8516505 TI - [Platelet hyperactivity in diabetic retinopathy: etiologic factor or epiphenomenon of microangiopathy?]. AB - In order to analyze the etiologic and pathogenic meaning of platelet activity in diabetic retinopathy, Plasmatic Beta-Thromboglobulin (BTG) has been determined in 42 diabetics without retinopathy, 14 diabetics with non proliferative retinopathy and in 29 health controls. BTG showed higher values in diabetic patients with retinopathy in comparison with diabetics with no retinopathy (46.4 +/- 10.7 versus 37.6 +/- 13.4 ng/ml; p < 0.05 and with controls (31 +/- 18.8; p < 0.005). There were no differences between diabetics with no retinopathy and controls. No relation was found between BTG and the glycemic control grade, neither with lipoproteic profile. In resume, platelet hyperactivity found in patients with retinopathy seems to be an epiphenomenon of the microangiopathic lesion and not an etiologic factor, however this not precludes that it can play a role in the progression on retinal lesions. PMID- 8516506 TI - [Epidemiology of Chlamydia trachomatis in a population attending a family planning center]. AB - OBJECTIVE: To know the prevalence of Chlamydia trachomatis in a population attending a Family Planning Center, as well as the distribution of said prevalence in relationship with different variables. METHODS: This was a prevalence study, population-based. So all females over 14 years old who consulted the Planning Center were admitted into the study. We used enzyme-immune assay and DNA probe to identify the microorganism. The statistical analysis used chi 2 and Fisher's exact test when needed. For the confidence intervals, Cornfield's test was used. RESULTS: Of the 2,408 female who participated in the study we found a prevalence of 5.1% this percentage was even higher on the 15 to 21 years old segment: 7.47% p < 0.05. Being single and belonging to the group of non-qualify workers yielded a relative risk of 1.49 and 1.66 respectively. CONCLUSIONS: The prevalence we have found is higher to the one found in different publications in our country, a study to determine Chlamydia trachomatis should be performed in all sexually active women between 15 and 30 years old. PMID- 8516507 TI - [Gammagraphic diagnosis of a non-hyperactive suprarenal adenoma]. AB - It is described the case of a patient with Ovarian Cystadenoma in whom a 3.5 cm nodular lesion was accidentally detected in her left suprarenal gland. She had no signs of hypercortisolism or any other suprarenal pathology and was symptomless. Determinations in the urine of 24 hours of Cortisol, Adrenaline and Noradrenaline, 17-ketosteroids and Tetrahydroaldosterone were normal. Daily rhythm and plasmatic determinations of ACTH, cortisol and 11-deoxycortisol were normal. The Dexamethasone suppression test was also normal. In the suprarenal gammagraphy it appeared an intense captation by left suprarenal without visualization of right gland. A left suprarenalectomy was performed and the anatomopathological analysis showed a clear cell corticoadrenal adenoma. Therefore the only data of the function of suprarenal adenoma was the one coming from gammagraphy. We thought that the adenoma was responsible of practically all the corticoadrenal function without reaching pathological levels, meeting the criteria of "pre-Cushing" syndrome or subclinical Cushing, due to the fact that the contralateral gland was not seen in the gammagraphy. Therefore in the characterization of certain tumors which appear clinically and biochemically as non functional, the suprarenal gammagraphy could be a technique of great usefulness for the diagnosis. PMID- 8516508 TI - [Pseudo-thrombophlebitis syndrome: diagnostic and therapeutic considerations of 2 cases]. AB - Pseudo-thrombophlebitic syndrome is a frequent clinical entity but many times insufficiently diagnosed. Described more than a century ago by Baker it is characterized for being clinically undistinguishable from a true thrombophlebitis, being its cause the presence of a synovial cyst in the knee joint (Baker's cyst) which can be complicated or not (breakage or dissection). Diagnosis is easy and is based mainly in echography and arthrography. The anticoagulant therapy used in true thrombophlebitis is contraindicated in this syndrome. PMID- 8516509 TI - [Pure motor hemiparesis secondary to chronic subdural hematoma with total recovery through medical treatment]. AB - We discuss in this paper the cases of two patients with pure motor hemiparesis which were secondary to chronic subdural hematoma who evolved satisfactorily only with medical treatment. Of 1,000 consecutive patients with cerebro-vascular pathology admitted in our Neurology Department in the last 5 years, said two patients were the only ones (0.2%) in whom the lacunar syndrome "pure motor hemiparesis" was secondary to a chronic subdural hematoma. Such cases show that a subdural hematoma can manifest itself as a lacunar syndrome and that in selected cases the medical treatment of chronic subdural hematoma can yield goods results. PMID- 8516510 TI - [Thoracic actinomycosis. Presentation of 3 cases]. AB - We have had the chance to follow three patients with thoracic actinomycosis in a relatively short period of time (18 months). They were three male patients, with chronic dental infections. The illness appeared as toxic syndrome and fever. In all three cases diagnosis was made through samples obtained through fibropticbronchoscopy. At the same time all of them evolved favorably to the antibiotic treatment (penicillin and/or tetracyclines) prescribed. We conclude that the diagnosis of thoracic actinomycosis should be suspected in those patients with a compatible clinical and radiological condition, and who has suffered previous weakening diseases and periodontal lesions. PMID- 8516511 TI - [Prognostic factors in differentiated thyroid carcinoma]. PMID- 8516512 TI - [Multiple brain lesions with negative serology in cerebrospinal fluid in a patient with AIDS and pulmonary tuberculosis]. PMID- 8516513 TI - [Acute pancreatitis from erythromycin]. PMID- 8516514 TI - [Clarithromycin in the treatment of cerebral toxoplasmosis associated with HIV infection]. PMID- 8516515 TI - [Cardiac effects of cocaine: apropos of a case]. PMID- 8516516 TI - [Refractory anemia with blast crisis and cerebral oligodendroglioma. An infrequent association]. PMID- 8516517 TI - [Mediterranean boutonneuse fever: forms of presentation and rare complications. Apropos of 2 cases]. PMID- 8516518 TI - [Visceral leishmaniasis in patients infected by HIV. An AIDS diagnostic criteria?]. PMID- 8516519 TI - [Statistical significance or clinical relevance. A question of sample size]. PMID- 8516520 TI - [Cardiorespiratory evaluation of midazolam and thiopental during their use in patients undergoing translumbar aortography in decubitus prone position and ASA IV]. AB - AIMS: To verify the cardiorespiratory effects of midazolam and thiopental in ASA IV patients undergoing translumbar aortography in the decubitus prone position. METHODS: A prospective double blind study was carried out on 26 patients (mean age, 65.9 yr) allocated randomly to receive either midazolam (0.13 mg/kg) or thiopental (4 mg/kg) i.v. Without being premedicated all the patients had fentanyl 1.5 micrograms/kg i.v. and were preoxygenated with 50% oxygen before induction of anaesthesia. Blood pressure was measured by oscilometry and blood oxygenation by pulseoxymetry. RESULTS: No significant differences were found in the hemodynamic values (blood pressure, heart rate, double product) upon comparison of the two groups. Apnea was more frequent in the thiopental group 61.5% (8 out of 13 patients) than in the midazolam group 15.3% (2 out of 13 patients). Hypoxemia appeared only in the former group (61.5% of the cases). CONCLUSIONS: In patients undergoing translumbar aortography midazolam and thiopental behaved similarly with regard to hemodynamics. Midazolam produced less apnea than thiopental. PMID- 8516521 TI - [Thoracic paravertebral blockade: postoperative analgesic effectiveness and plasma concentrations of bupivacaine]. AB - AIMS: To compare the analgesic efficacy of thoracic paravertebral blockade with that of endovenous morphine to measure the plasma levels of bupivacaine and to study the complications derived from both techniques in patients undergoing thoracic or abdominal surgery with unilateral incision. METHODS: Twenty ASA I-II patients allocated to two groups (A and B) of ten patients each were studied. Group A (5 cholecystectomies and 5 thoracotomies) received morphine 0.075 mg/kg i.v. every 3 hours after operation. Group B (5 cholecystectomies and 5 thoracotomies) received thoracic paravertebral blockade 15 ml of 0.37-5% bupivacaine with 1:200.000 adrenaline following tracheal extubation. Analgesia was evaluated according to the visual analogic scale (VAS) with laterality and extension of the blockade being assessed. The plasma levels of bupivacaine were measured by liquid chromatography in 5 patients. Blood pressure, heart rate and respiratory frequency were assessed in both groups. In group B the appearance of pneumothorax or other local complications were noted. The results were statistically analyzed using to the Student's test. RESULTS: The patients in group A presented significantly more pain than those of group B. In these patients analgesia was unilateral. Plasma levels ranged between 0.56 mg/l at 5 minutes of administration and 0.17 mg/l at 240 minutes with a peak of 0.70 mg/l at 10 minutes with all these values being considerably lower those a determined as toxic (2-4 mg/l). No significant differences were found between the values of blood pressure, and cardiac and respiratory frequency of both groups. There were no complications derived from the technique. CONCLUSIONS: Thoracic paravertebral blockade is a very effective postoperative analgesic technique and is superior to that of i.v. morphine in patients undergoing thoracic or unilateral abdominal surgery. Peak plasma levels were much lower than those considered as toxic complications of interest were observed. Therefore, this technique may be considered as an alternative to other blockades such as extradural, interpleural or intercostal. PMID- 8516522 TI - [Omeprazole in the prophylaxis of Mendelson syndrome in elective surgery]. AB - AIMS: To study the efficacy of different doses of omeprazole and the influence of premedication in the prophylaxis of the acid aspiration syndrome. METHODS: A double blind prospective study was carried out ASA I-III on 103 patients (mean age 51.08 yr) undergoing either general, gynecological or orthopedic surgery, allocated into 4 groups. Group NP: 24 non premedicated patients; group P: 29 patients premedicated with 1 mg of lorazepam the previous night and 50 mg of meperidine 1 hour before surgery and haloperidol or dipotassic chlorazepate according to age; group 020: 25 patients premedicated with the same drugs and doses as in group P plus 20 mg or oral omeprazole the night prior to surgery; group 040: 25 patients premedicated as in group P 40 mg of oral omeprazol the night prior to surgery. Following induction of anesthesia a nasogastric tube was placed and gastric juice withdrawn to determine the pH; were excluded patients with an aspiration volume of less than 8 ml. RESULTS: No significant differences were found in regard to pH among the non premedicated and premedicated groups, however a change between the latter two groups having received omeprazole was observed. The results of the pH were significantly higher in the group treated with 40 mg of omeprazole (mean 4.87 +/- SD 2.35) with respect to the group treated with 20 mg of omeprazole (mean 3.78 SD +/- 2.35). In the group treated with 40 mg of omeprazole, the incidence of pH < 1.5 was 4% vs 24% of cases in the group treated with 20 mg of omeprazole. CONCLUSIONS: Premedication with 40 mg of oral omeprazol the night prior to surgery increases pH up to safe values for the prophylaxis of the acid aspiration syndrome. PMID- 8516523 TI - [Intubation with propofol without neuromuscular blockade. Effect of premedication on fentanyl and lidocaine]. AB - AIMS: Laryngotracheal reflexes, and possibilities of intubations following anaesthetic induction with propofol, with or without premedication and without neuromuscular blockade were evaluated. Hemodynamic parameters were also measured. METHODS: Sixty ASA I-II patients were randomly allocated into 3 groups according to anaesthetic premedication. Group P: (placebo), 2 and 4 ml of saline 0.9%; group F, 4 micrograms/kg of fentanyl and 2 ml of saline 0.9%; group L, 4 micrograms/kg of fentanyl and 1.5 mg/kg of lidocaine 5%. Two point five mg/kg of propofol were administered and 45 seconds later intubation was attempted. Mandibular relaxation, visualization of the glottis, opening of the vocal chords, reflex reactions to laryngoscopy and intubation, time used, blood pressure and heart rate were evaluated. RESULTS: Mandibular relaxation and visualization of the glottis were acceptable in all the patients. The aperture of the vocal chords was enough so as to carry out intubation in 65% (P), 100% (F) (p < 0.05) and 95% (L) (p < 0.05). Laryngeal reactivity significantly decreased (p < 0.001) from 40% (P) to 15% (F) and 10% (L). Tracheal reflexes decreased from 84.6% (P) to 55% (F) (p < 0.01) and 37% (L) (p < 0.001). Blood pressure and heart rate rose with intubation over the basal levels in group P and significantly decreased in groups F and L. CONCLUSIONS: The use of propofol without neuromuscular blockade is inadequate for intubation since laryngotracheal reflexes are not suppressed. Besides, propofol does not prevent hemodynamic reactions. Premedication with fentanyl and/or lidocaine improves the responses not sufficiently to safely perform intubation. PMID- 8516524 TI - [Anesthetic considerations in patients with human immunodeficiency virus infection]. AB - In the last few years many articles have been published on AIDS, the mechanism of transmission, prophylaxis and therapeutic possibilities; however, very few publications are available related with anesthesia of patients infected with HIV or AIDS. The authors have therefore undertaken this review in which following a brief description of the etiology, pathogenesis, physiopathology and treatment of the disease, the problems of anesthesia are specifically dealt with. The need for knowing the different active or latent clinical alterations, such as neurologic (encephalitis, meningitis, peripheral neuropathies, myelopathies, etc.), respiratory (pneumonias by Pneumocystis carinii), cardiovascular (myocardiopathies), digestives (oropharingeal candidiasis, hepatopathies), psychologic (drug addiction), hematic (anemias, leucopenias) coagulopathies, nephropathies, etc. must be emphasized. Before the possibility of such a broad pathology good evaluation and preoperatory preparation is essential. With regard to anaesthetic technique, regional anesthesia is of choice except in certain cases of neuropathies. Although patients with a high degree of immunosuppression present a high risk of infections of the nervous system, the global risk is lower than if general anesthesia with prolonged artificial respiration were received. PMID- 8516525 TI - [Cardiac arrest in newborn of mother treated with labetalol]. AB - The use of beta-adrenergic antagonists for the control of high blood pressure associated to pregnancy is frequent. Their use is related with the appearance of undesirable effects of the fetus. The case of neonatal cardiac arrest attributed, to the administration of labetalol to the mother is presented. The high transplacentary passage, the different pharmacokinetics of the drug in the newborn and the clinical evolution of the patient suggests its involvement. It is concluded that labetalol may cause severe undesirable effects in newborns and fetal heart rate of the mother and neonate should be monitored upon use of this drug. PMID- 8516526 TI - [Acute pancreatitis after resection of abdominal aortic aneurysm]. AB - The case of a patient who developed acute pancreatitis following resection of a ruptured aneurysm of the abdominal aorta is presented. During the first postoperative days the patient evolved satisfactorily except for specific abdominal symptoms. On the sixth day the patient suddenly presented tachycardia, hypotension, increase in abdominal distension and anemia for which emergency laparotomy was performed with signs of diffuse peritoneal steatonecrosis with an increase in the size and inflammation of the pancreas with necrotic and hemorrhagic zones being observed. The patient developed multiorganic failure and died at 18 days later. In this case, as in others described in the literature the beginning was uneventful. Only the determination of amylase and/or lipase, and the performance of abdominal CAT when these are increased, may be useful to obtain early diagnosis. PMID- 8516527 TI - [Cerebral infarction, respiratory arrest, and coma after percutaneous catheterization of the right internal jugular vein]. AB - The case of a 76 year old patient diagnosed of severe dysphagia by familiar oculopharyngeal muscular dystrophy is presented. Central venous catheterization (right internal jugular) was required for parenteral nutrition. A few minutes after catheterization, the patient developed respiratory arrest and coma and later cerebral vascular accident with left flaccid hemiplegia, with the ischemic lesion being focalized in the right parietooccipital region as well as in the left of the posterior fossa were observed. Aneurismatic dissection of the bilateral vertebral artery during lateralization of the head may be a cause of the lesions presented by the patient associated to arterial spasm or not. In central venous catheterization the possible complications derived from the position of the neck may carry must be taken into account. PMID- 8516528 TI - [Anesthesia in a case of glucagonoma]. AB - The case of a patient with all manifestations of pancreatic glucagonoma is presented. The real prevalence of this disease is unknown for in many cases there are no clinical manifestations. It is usually an accidental finding during autopsy and it is considered as an infrequent entity. Patients with glucagonomas may have different hydroelectrolytic and metabolic changes causing myocardial dysfunction and thromboembolic alterations. Anesthesia for this type of patients requires a strict control of glycemia, a careful evaluation of the nutritional and hydroelectrolytic state and adequate thromboembolic prophylaxis. PMID- 8516529 TI - [Patient monitoring in neurosurgery]. PMID- 8516530 TI - [Subacute subdural hematoma after cranioencephalic trauma in an alcoholic patient]. PMID- 8516531 TI - [Inhalation anesthesia at the end of the 19th Century]. PMID- 8516532 TI - [Which information can we get from the "Barcelona" databank?]. PMID- 8516534 TI - [Murmur, contrast, color...? The evaluation of mitral prosthetic regurgitation from the clinical perspective]. PMID- 8516533 TI - [Transesophageal echocardiography in mitral prosthesis dysfunction: usefulness and limitations in the evaluation of mitral insufficiency]. AB - This study was performed to test the usefulness of transesophageal echocardiography in the diagnosis and assessment of pathological mitral regurgitation in patients with mitral valve prostheses. Doppler color flow imaging by transesophageal echocardiography was compared to the transthoracic echocardiography and angiographic and surgical assessment. We analyzed the influence of the spatial configuration of the jet on the semiquantitative assessment of mitral regurgitation. We studied 71 patients with prostheses in mitral position which were submitted for transesophageal echocardiography examination. 51 of these patients were found to have a pathological prosthetic regurgitation that was confirmed in 21 cases by left ventriculography and in 4 during cardiac surgery. Transesophageal echocardiography Doppler color flow imaging identified a regurgitant jet in 31 patients (60.7%). There was complete agreement with the quantitative assessment of regurgitation by angiography or surgery in 36% of the cases. All patients with prosthetic insufficiency observed by angiography or during cardiac surgery were confirmed by transesophageal echocardiography. Complete agreement in grade of severity by transthoracic echocardiography was found in 84% of cases. There was a difference in grade of severity of mitral regurgitation in only 4 patients. Regurgitant jets were classified by transesophageal echocardiography color Doppler in two groups: free jets and impinging wall jets. 21 cases presented a free jet and 31 excentrically directed impinging wall jet of mitral regurgitation. There was complete agreement with hemodynamic assessment of severity in all patients with regurgitant free jets (11/11). In presence of jet wall there was understimation of mitral regurgitation in 28.5% (4/13).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516535 TI - [Usefulness of carotid sinus massage for Doppler quantification of mitral stenosis in sinus rhythm]. AB - The quantification of mitral stenosis by pressure half-time method may be difficult in sinus rhythm with short deceleration slopes. To evaluate the usefulness of carotid sinus massage (CSM) for measuring mitral valve area by pressure half-time, 80 consecutive patients with mitral stenosis in sinus rhythm underwent a echo-Doppler study at basal heart rate and during right CSM. In both situations we measured: heart rate, mitral area by pressure half-time and E-F interval (time from E peak velocity to onset of atrial contraction). In 38 consecutive patients we also determined the mitral area by planimetry. The study group was divided into patients with basal E-F interval < or = 150 ms and a HR > or = 75 bpm (group A, 28 patients [35%]) and those with a basal E-F interval > 150 ms who showed a heart rate < 75 bpm (group B, 52 patients). In the group A, the values obtained at basal heart rate vs after CSM were: heart rate, 86 +/- 9 vs 61.6 +/- 10.5 lpm; E-F interval, 109 +/- 33 vs 372 +/- 136 ms; mitral area, 1.88 +/- 0.5 vs 1.23 +/- 0.29 cm2 (p < 0.001). In the group B, these values were: 69.7 +/- 6.6 vs 53 +/- 11 bpm, 253 +/- 60 vs 510 +/- 212 ms y 1.34 +/- 0.3 vs 1.18 +/- 0.32 cm2, respectively (p < 0.01). Mean differences in Doppler mitral areas between both situations for groups A and B were: 0.63 +/- 0.3 cm2 and 0.17 +/- 0.1 cm2, respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516537 TI - [Evaluation of the surgical correction in complete atrioventricular channels]. AB - We review our experience of surgical correction in atrioventricular canals between 1979 and 1991. 81 patients, ranging in ages from 5 to 109 months (with an average of 33 months) and weight from 4 to 25 kg (with an average of 9 kg), underwent primary repair. Another cardiac anomalies associated were ruled out, except patency of the arterial ductus. 33 patients (46%) presented the complete form of atrioventricular canals, 27 (33%) the partial form and 17 (21%) the transitional form. 55 patients (68%) of the sample had Down's syndrome. Regarding the cases with the complete form they were frequently associated to Down's syndrome. Thus, 89% of the cases of complete form had Down's syndrome. All operations for complete form cases used a two-patch technique and physiological reconstruction of the left atrioventricular valve. No patient underwent pulmonary artery banding or was discharged from surgery correction due to pulmonary pressure or resistance. The average age of the children with complete form was 19.5 months (11 months from 1986). The main hemodynamic parameters were mean pulmonary arterial pressure of 57 +/- 12 mmHg, pulmonary-systemic pressure relation of 0.87 +/- 0.12 and total pulmonary resistance of 6.3 +/- 4.0 U/m2. The hospital mortality was 32% in the complete form, comparable to samples of similar characteristics. We related this mortality with the hemodynamic profile at the time of surgical correction, compatible with pulmonary vascular obstructive disease, with the elevated percentage of Down's syndrome and with the delay in the surgical operation age. PMID- 8516536 TI - [Experience with the Palmaz-Schatz stent in the treatment of postangioplasty coronary dissection]. AB - Some authors have proposed the use of coronary stenting as a good therapeutic strategy for post angioplasty acute coronary dissection. We present our experience with the Palmaz-Schatz stent for the treatment of acute coronary dissection after percutaneous coronary angioplasty. Twenty five stents were deployed in nineteen patients with occlusion (7) or threatened occlusion (12). Eleven patients (58%) had multivessel disease, seven (37%) unestable angina and six (32%) previous myocardial infarction. The attempted lesion was type A in four patients (21%), type B in thirteen (68%) and type C in two (11%) according to the American College of Cardiology/American Heart Association classification. To cover the dissection was necessary to deploy three stents in two patients, and two stents in two more. The other fifteen patients received one stent each. In eighteen patients (95%) the stent deployment was accomplished with immediate angiographic success. Twelve stents were deployed in the right coronary artery, eight in the left anterior descending and five in the circumflex. In sixteen patients (84%) the stent successfully solved the occlusion or threatened occlusion reassuming a normal coronary flow. There were 10 complications in six patients: one death (5%), 3 cases of emergency coronary artery bypass graft (16%), 2 acute myocardial infarction (11%), 2 hemorrhagic complications (11%) and 2 cases of subacute thrombosis of the stent (11%). The Palmaz-Schatz stent seems to be a useful tool for the management of acute coronary dissection with a fair number of complications. The results obtained during hospitalization are maintained with a more than acceptable restenosis rate. PMID- 8516538 TI - [Clinical evaluation of the changes produced by nitrates in patients with chronic heart insufficiency]. AB - The aim for this study was to evaluate the hemodynamic changes that appear in patients with myocardiopathy at functional stage II (NYHA) subjected to standard treatment (digital+diuretics) plus nitrates. We used isosorbide-5-mononitrate (IS 5-MN). We studied 20 patients for 100 days in different phases. The placebo controlled, crossover, double-blind stage random distribution was from day 2 to 5. From day 6 to 20 all the patients took 40 mg/12 hours of IS-5-MN, taking 40 mg/8 hours of active ingredient from day 21 to 100. We performed basal cycloergometrics 3 and 6 hours after administration on days 2, 5, 20, 34 and 100 of the treatment, as well as echocardiograms on these same days. We compared the results obtained versus placebo (p < 0.05). There were no significant differences in heart rate at rest or systolic arterial tension at rest or maximum. Maximum heart rate increased significantly in the tests at days 34 (basal: 143 +/- 9; 3 hours: 139 +/- 8; 6 hours: 140 +/- 7) and 100 (basal: 145 +/- 7; 3 hours: 141 +/- 8; 6 hours: 142 +/- 6) versus the tests carried out with placebo (basal: 136 +/- 8; 3 hours: 135 +/- 7; 6 hours: 136 +/- 7). There were no differences in the tests after acute dose or at treatment day 20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516539 TI - [Intranodal tachycardia. Ablation of the fast and the slow pathway]. PMID- 8516540 TI - [Prolonged asystole requiring resuscitation techniques during head-tilt table test]. AB - We describe a case of a patient with recurrent syncope without cardiac disease and with a normal electrophysiological study. The patient underwent a head-up tilt table test as a diagnostic method. During the test the individual suffered a twenty-nine seconds cardiac asystole. He recovered the cardiac rhythm nineteen seconds after having adopted the supine position and with resuscitation maneuvers. In the consulted bibliography, there is no evidence of such a long asystole induced during a head-up tilt table test, where the patient required a chest thumping. Commonly the spontaneous recuperation of the cardiac rhythm takes place immediately after the patient adopts a horizontal position. This case supports the hypothesis that the asystole provoked by a cardioinhibitor reflex in patients suffering from a vasovagal syncope, can become potentially lethal and therefore lead to sudden cardiac death. PMID- 8516541 TI - [Late diagnosis of heart rhabdomyoma with echocardiography]. AB - We describe 2 cases of tuberous sclerosis in a 17 and a 27 years old patients in which images compatible with a cardiac rhabdomioma were detected during an echocardiographic study. In one of the cases these images were multiple. We point out the few clinical repercussions they caused and the length of their undetected presence. We revise the clinical features and diagnosis of these rare tumours and comment on the need to withhold surgical treatment in situations which could put the patient's life in danger. PMID- 8516542 TI - [Usefulness of Doppler color echocardiography in the treatment of femoral pseudoaneurysms]. AB - Four patients with a femoral pseudoaneurysm formation after a therapeutic cardiac catheterization are presented. The diagnosis was made by color-Doppler-ultrasound after clinical suspicion. The repair of this complication was performed using color flow ultrasound-guided compression of the pseudoaneurysm neck. PMID- 8516543 TI - [Papillary muscle rupture. Diagnosis with transesophageal echocardiography]. AB - Two patients with acute myocardial infarction and papillary muscle rupture are presented. The diagnosis of papillary muscle rupture was made by transesophageal echocardiography. The transesophageal echocardiographic findings and the usefulness of this technique in the diagnosis of papillary muscle rupture are described. PMID- 8516544 TI - [Prognosis of myocardial infarction in women. Effect of the therapeutic effort and socioeconomic level]. PMID- 8516546 TI - [The new training of physicians in Italian universities. Is it useful to evaluate the didactic activities and their results?]. PMID- 8516545 TI - [Monsters and non-monsters. Psychiatric diagnosis and criminological diagnosis]. PMID- 8516547 TI - [The relation of moderate alcohol drinking and congestive heart insufficiency]. AB - 116 patients (53 women and 63 men) with congestive heart failure, secondary to chronic ischemic heart disease and/or hypertensive heart disease, were studied with the aim of assessing effects of moderate alcohol use on the clinical features of the disease. Two subgroups were considered: a) 57 moderate drinkers (11 women and 46 men); b) 59 non-drinkers or ex-drinkers (42 women, 17 men). Left ventricular mass/m2 (LVM/m2) is higher among moderate drinkers in comparison with non-drinkers (p < 0.001); this difference is present both in men (p < 0.05) and in women (p < 0.001). These results suggest that higher LVM/m2 of drinkers does not depend on sex and cigarette smoking; i.e., in males, a subgroup with the same prevalence of cigarette smokers among drinkers and non drinkers, congestive heart failure of drinkers is associated with a greater left ventricular enlargement. Our results suggest that moderate alcohol use can represent an additional pathogenetic factor for more severe clinical and laboratory features of congestive heart failure. PMID- 8516548 TI - [p55 and p75 subunits of the IL 2 receptor, membrane bound and soluble, in peripheral lymphocytes in patients with solid tumors]. AB - The aim of the investigation was to directly study the IL 2 receptor (IL 2 R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on peripheral blood mononuclear cells (PBMC) of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL 2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 years, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e. breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL 2 and IL 2 was evaluated along with the response to PHA in presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL 2 R, p55 and p75 chains, on PHA-stimulated PBMC were detected, along with soluble IL 2 R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane bound IL 2 R s, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL 2 R, there is a normal release of soluble IL 2 R in culture, and there is an indirect evidence of a lack of IL 2 production. Therefore, no primary impairment of IL 2 R was found in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516549 TI - [IgD myeloma: an aggressive variant. Description of a clinical case and review of the literature]. AB - It is shown a case of IgD myeloma, a rare type of myeloma having often an aggressive course. Besides to confirm clinical and laboratory aspects already known in literature, this case seems to make in evidence a rapid neoplastic proliferation kinetic, difficult to be controlled by conventional chemotherapy. The Authors show that the M component low concentration and the unbalance of the synthesis of the immunoglobulin heavy and light chains may confuse IgD myeloma with light chain myeloma. PMID- 8516550 TI - [Cleidocranial dysostosis]. PMID- 8516551 TI - The effect of venous occlusion on high and low-density lipoproteins. PMID- 8516552 TI - The effect of venous occlusion on fibrinolytic potential and plasma storage at 20 degrees C or -70 degrees C. PMID- 8516553 TI - [New horizons in medicine. Fractals]. AB - In these last few years, a vertiginous growth in the application of informatics in the field of science has generated a new branch of geometry: the geometry of irregularity whose paradigmatical expression is fractals. We can identify in the fractal an object of complex structure which, when gradually enlarged, shows up details which repeat themselves as the scale of enlargement is progressively run through. It is possible, therefore, by using fractals to study and quantify in a much more concise way and much less approximatively those structures which were until recently described as granulous, tentacular, ramified, etc. Fractals bridge the gap between mathematics and visual art and allow us to explore the rapport between determinism and apparent chaos in the study of non-linear biological systems. Fractal dimension is an intermediary one between linear and surface dimensions. The applications of fractals images in the study of certain problematics which concern the cardiovascular system are referred to synthetically; particularly those concerning the sectorial differences of myocardial blood flow and the branches of small coronary vessels, both in physiological and pathological conditions. Fractal images permit us to analyse the regional flow of the pulmonary parenchyma, and to quantify pulmonary damage from thromboembolism. Other applications of fractal studies regard the digestive system, the nervous system and mammary pathology. In specialistic fields, fractals have been studied in both ophthalmology and odontology, and also in biochemistry to study protein surfaces and fluids turbulence. PMID- 8516555 TI - [Nutrition and malnutrition in hepatic cirrhosis]. AB - Liver cirrhosis is associated with malnutrition in 10 to 90% of cases, following different authors. This prompted us to compare our previous studies with recent literature data in order to review this topic from a practical standpoint. Several pathophysiological factors are blamed for this state and mainly protein and lipid-restricted diets from among these. Some lean and fat body mass indices predictive of malnutrition are proposed taking into account the influence of liver disease in their evaluation. Nitrogen balance derangements and liposoluble vitamins and carotenoids plasma decrease are highlighted as sensitive nutritional parameters. After a brief review of amino acid, glucose and lipid metabolic derangements, some nutritional guidelines are provided by distinguishing oral selective supports from the parenteral nutrition. The latter, being reserved to moderate-severe encephalopathy or to hemorrhagic conditions, is proposed following an algorithm which takes into account different nutritional principles as a function of the severity of the clinical condition. During the first period (24-48 hrs) parenteral fluids, electrolytes, dextrose and whole blood or derivatives (when necessary) are provided; lactulose or lactitol via nasogastric tube, or by enema, are started as well. During the following 48-72 hrs branched chain amino acids alone or enriched solutions are added taking into account an optimum calorie/nitrogen ratio. Finally, vegetable lipids, vitamins and oligoelements can be added if intravenous nutrition must be maintained, with a view of warranting the most complete nutritional approach to these severely malnourished patients. PMID- 8516554 TI - [Vasovagal syncope]. AB - The nature of most syncopal episodes, previously unknown, was recently elucidated by new diagnostic techniques such as the use of the tilt test. The vasovagal syncope can be clinically diagnosed by means of the tilt test. The transitory loss of consciousness during prolonged orthostasis is typically associated with sudden hypotension and bradycardia, which are commonly preceded by relative tachycardia and by premonitory symptoms such as pallor, nausea, asthenia, yawns, hyperventilation, mydriasis, humming, lasting several minutes. The nature of the vasovagal reflex is now better understood: in subjects with vasovagal syncope, during prolonged orthostasis, it was observed a fall in the venous return, inducing an increased sympathetic drive to the heart (with positive inotropic and chronotropic effect) and a lower ventricular filling. The powerful contraction around an almost empty cardiac chamber induces the activation of ventricular mechanoreceptors, and through a reflex mechanism, a sudden increase in the vagal and a sudden reduction in the sympathetic drive. These autonomic changes are responsible for a sudden hypotension and bradycardia. The discussion is still open about the origin of the reduced venous return: it probably originates from a redistribution in the blood volume, due to a venous pooling in the lower limbs or from a reduced muscle tone, because many subjects with vasovagal syncope are slender and with less developed muscle apparatus. Others suggest that a reduction in the sympathetic drive to the vessels, responsible for a progressive hypotension in the minutes preceding syncopal episodes, is the origin of the reduced venous return. In this review a diagnostic pattern for the assessment of the vasovagal syncope is suggested. The medical history, clinical examination, electro- and echocardiogram, chest x-ray identify two main groups of patients (with or without cardiopathy) who will follow different diagnostic protocols. The therapy of vasovagal syncope, which is based on beta-blockers, scopolamine, dysopiramide and plasma expanders, is reviewed. PMID- 8516556 TI - [HIV-induced clinical conditions: rheumatic conditions]. AB - Many retroviruses have been shown to be involved in the etiology of rheumatic diseases both in animal models and in humans. In particular, HIV infection has been correlated to a greater incidence of Reiter syndrome, psoriatic arthritis, sicca syndrome and other seronegative polyarthritides. Aim of this paper is to discuss clinical findings, diagnostic strategies and therapy of these diseases. We will describe how the profound abnormalities in the immune system brought about by the HIV infection can induce the development of reactive arthritides, inhibit the clinical expression of rheumatoid arthritis and affect the clinical presentation of SLE. PMID- 8516557 TI - The in vivo antibody response in rat gut-associated lymphoid tissue (GALT) after immunization with bacterial polysaccharide antigen. AB - Gut mucosal immune responses to bacterial polysaccharide antigen in rats were investigated in vivo. Rats were immunized with pneumococcal polysaccharide type 3 (PPS-3) via different routes, i.e. in the Peyer's patch (iPP), in the colon (ic), in the peritoneal cavity (ip), and intravenously (iv). The development of specific antibody-forming cells (AFC) and their isotypes in the intestinal mucosa, gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN) and spleen were studied by immunohistochemistry. Furthermore, the serum antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that iPP immunization evoked high numbers of anti-PPS-3 AFC of the IgA isotype in the mucosa of the small intestine and in the PP. On the contrary, the ic route did not elicit a mucosal response, though a few AFC were found in the MLN and spleen. Following ip priming, a specific IgA response was found, especially in MLN and spleen, and a low response was detected in the villi. A high response was found in the parathymic lymph nodes (PTLN). Iv immunization gave rise to the development of AFC in the spleen, particularly of the IgM isotype. We failed to induce mucosal responses to PPS-3 antigen in the colon, irrespective of the route of immunization. PMID- 8516558 TI - Fc gamma R-expressing monocytes are necessary for PWM-induced proliferation of Saimiri sciureus peripheral blood mononuclear cells. AB - When used as a polyclonal activator of blood immunocompetent cells in the squirrel monkey, pokeweed mitogen (PWM) failed to induce lymphoproliferation unless either autologous or human serum was added to the culture medium, instead of a serum assumed to be deprived of Ig such as foetal bovine serum. We thus attempted to delineate activation processes initiated by PWM and which required both monocytes and native Ig molecules. For instance, the physical presence of live monocytes within lymphocyte suspensions vs. paraformaldehyde-fixed monocytes or products of monocytic origin was an absolute prerequisite for inducing squirrel monkey lymphocytes to proliferate in the presence of PWM. In addition, a combination of monocytes and native Ig were further shown to induce lymphocytes to proliferate in the presence of PWM. We therefore questioned whether Fc gamma R on the surface of monocytes vs. Fc gamma R expressed by other cells were involved in the initiation of PWM-driven lymphoproliferation. PWM may represent a useful tool for studies of Fc gamma R-mediated immunological processes. PMID- 8516559 TI - Efficient immunoselection of cytolytic effectors with a magnetic cell sorter. AB - This paper describes a rapid and efficient method for the sorting of in vitro activated cytolytic effectors cells. For cytotoxic assays, a large number of cells with conserved function must be rapidly obtained. Immunomagnetic sorting was chosen because it is faster than flow cytometry sorting. The MACS system requires the use of paramagnetic beads of small diameter (100-150 nm), reputed to interfere minimally with cell function. In order to generate the cytolytic effectors, peripheral blood lymphocytes were cultivated in the presence of interleukin-2 (50 U/ml) and anti-CD3 monoclonal antibody (BMA030, 100 ng/ml) for 4 days. Cell separation was based on the membrane expression of the CD3 complex. The purity obtained for positive (CD3+) cell sorting with the MACS was higher than 95%. The purity of negative (CD3-) cell fraction was more variable, but further purification by flow cytometry rapidly yielded purity higher than 95%. Cytotoxic assays were performed against four target cell lines (K562, Daudi, HL60 and U937) and proliferation assays showed that both negatively and positively selected populations had conserved their function acquired during culture in the presence of anti-CD3 mAb and IL2. PMID- 8516560 TI - Interaction of two DNA-binding factors expressed in B- and T-lymphocyte precursors. AB - Two DNA-binding factors detected in pre-B and pre-T cells and absent from mature lymphocytes are described. Factor A displayed no appreciable sequence selectivity but bound only to DNA fragments longer than 120 base pairs. The minimal size of a binding site was lower on an intrinsically curved DNA, suggesting formation of tertiary structures on DNA. Factor B interacted with sequences, other than consensus recombination signals, present in the vicinity of unrearranged immunoglobulin genes. Binding of factor B inhibited the interaction of factor A with the same DNA fragment. The presence of the factor-B-binding site in an episomal V(D)J recombinase substrate lowered the frequency of recombination in vivo. We propose that the two factors described here may function as accessory proteins in V(D)J recombination, possibly modulating accessibility of genes to the recombinase. PMID- 8516561 TI - Signal processors in duplex sonography: in vitro comparison between analog and digital methods. AB - Using a new flow-test phantom, which respects the acoustic properties of real blood as well as the proximal and distal impedances of body circulation, we assessed the performance of two duplex sonography signal processors on blood-flow measurements. With both the analog and the dynamic signal processor (Fast Fourier Transform), the correlation between duplex sonography and quantitative flow measurements was high (0.96-0.99) for different dynamic conditions (steady or pulsatile blood flow, varying heart rate, blood pressure, and hematocrit) and for different mechanical conditions (silicon tube or animal vessel). The real blood flow was overestimated by duplex sonography; the over-estimation was more pronounced with the analog processor (factor 1.87-4.20) than with the digital processor (factor 1.22-1.64, P < 0.05). Applied to the study of asymmetric stenoses, the digital processor was not superior to the analog processors described in the literature. PMID- 8516562 TI - Phospholipase-resistant phosphatidylcholine reduces intra-abdominal adhesions induced by bacterial peritonitis. AB - The majority of intra-abdominal adhesions develop postoperatively or following peritonitis. We have previously shown that L-phosphatidylcholine reduces postoperative peritoneal adhesions in rats. In the present study, we examined whether adhesion formation after bacterial peritonitis is also reduced by L phosphatidylcholine or by DL-alpha-phosphatidylcholine, which is degraded only 50% by phospholipase A2. Peritonitis was induced in the rat by caecal ligation and double puncture; cecotomy was performed 12, 15, or 18 h later. Adhesions were assessed blindly by a scoring system 7 days after cecotomy. When cecotomy was scheduled for 18 h after caecal ligation and puncture, the 7-day mortality was 90% (n = 20). When cecotomy was performed at 12 h, no mortality was seen; however, the adhesion score was low (2.3 +/- 0.7). When cecotomy was performed 15 h after caecal ligation and puncture, the mortality was 25% and the adhesion score was 4.3 +/- 0.9. This figure was reduced significantly by intraperitoneal instillation of L-phosphatidylcholine or DL-alpha-phosphatidylcholine for 3 subsequent days. However, the mortality increased by L-phosphatidylcholine (P < 0.01), whereas mortality after DL-alpha-phosphatidylcholine remained at 30%. We conclude that administration of both L-phosphatidylcholine and DL-alpha phosphatidylcholine decrease adhesion formation after bacterial peritonitis. PMID- 8516563 TI - Reduction of HIV-1 antigen production by phosphatidylcholine containing formulations via growth inhibition of HIV-1-infected cells. AB - Phosphatidylcholine (PC) and licensed formulations containing PC were tested for their influence on the proliferation and viability of cells permanently infected with HIV-1 (human immunodeficiency virus type 1). PC alone, as well as pharmaceutical formulations containing PC, selectively inhibited the growth of productively infected lymphoid cells. The strongest growth inhibition was observed with formulations containing PC, glycerol and triglyceride together. The growth inhibition was dose-dependent for HIV-1-infected cells. Additionally, PC containing formulations dramatically reduced antigen production from peripheral blood mononuclear cells (PBMCs) infected in vitro with HIV-1. In vivo experiments with Rauscher-MuLV-infected mice showed that PC administered either intraperitoneally or orally was able to inhibit Rauscher-virus-induced splenomegaly. PC-containing formulations are currently used in man for supportive therapy at doses, which in vitro induced 50% growth inhibition of HIV-1-infected cells in vitro. Such doses have been used in man without side effects for many years. Thus, PC-containing formulations may be valuable for the treatment of HIV 1-infected individuals. PMID- 8516564 TI - Functional and morphological effects of defibrotide on renal ischemia. AB - Defibrotide (Df) has been reported to protect various organs from ischemic damage. The aim of this study was to evaluate the effect of Df on renal function and morphology after warm kidney ischemia. Divided into two groups, 14 pigs underwent bilateral renal clamping for 90 min. One group (7 pigs) was treated with Df (32 mg/kg per h) for 6 h, whereas the control group received 5000 IU of heparin. Serum levels of blood urea nitrogen (BUN) and creatinine measured for 6 days were significantly higher in the control group (peak 26.8 +/- 16.7 vs 11.0 +/- 2.9 mmol/l and 501.2 +/- 351.4 vs 230.2 +/- 68.0 mumol/l P < 0.05). Renal biopsy evidenced a lesser extent of tubular and endothelial damage in Df-treated animals. In conclusion, Df provided relevant protection against renal ischemic injury. PMID- 8516565 TI - Local hypothermia during ischemia or reperfusion in skeletal muscles. AB - A modified rat hindlimb tourniquet model was used to measure postischemic muscle necrosis. The effect of moderate local hypothermia to 20 degrees C during ischemia and reperfusion was investigated. Eighteen animals were kept in an incubator at 27 degrees C, and complete circulatory arrest was maintained for 3.5 h before release of the vascular occlusion. After survival for 72 h the degree of necrosis in the anterior tibial muscles was measured morphometrically on histological slides. Areas of necrosis with intact capillary structure and resorption of muscle fibers, and areas without resorption and capillary disintegration were measured separately. Three experimental groups (six animals in each) were included in the series. In the first group local cooling to 20 degrees C was performed during the initial 1.5 h of ischemia. The second group was cooled for 1.5 h during the initial phase of reperfusion. The animals in the third group served as controls without cooling. The total areas of necrosis in the three groups were 0, 90 and 90%, and the areas of no-resorption 0, 23 and 39%, respectively. Cooling during ischemia thus had a marked effect, while no significant differences were found between the control group and the group cooled during reperfusion. The study shows that moderate cooling during initial ischemia protects effectively against postischemic muscle necrosis, while cooling during reperfusion has no such effect. PMID- 8516566 TI - Altered energy metabolism and oxidative injury following endotoxemia in rats with normal or cirrhotic livers. AB - The release of oxygen-derived free radicals has been implicated in endotoxin mediated hepatic injury. The effect of hepatic lipid peroxidation on tissue energy reserves in the livers of normal and cirrhotic rats was studied following administration of E. coli endotoxin. Before endotoxin injection, the basal hepatic energy charge was lower and levels of hepatic malondialdehyde (MDA) and total glutathione (GSH) higher in cirrhotic rats than in normal rats. Virtually identical levels of blood endotoxin were obtained in the two groups 24 h after injection of LD50 doses of endotoxin (20 mg/kg and 1 mg/kg in normal and cirrhotic rats, respectively). Hepatic energy charge, tissue blood flow, GSH and glutathione peroxidase (GPX) were consistently or transiently decreased up to 24 h after the injection of endotoxin in both normal and cirrhotic rats. MDA, significantly increased in normal rats 1 h after injection of endotoxin, returned to normal levels 3-12 h after endotoxin administration, but was again elevated at 24 h. Cirrhotic rats did not show any significant change in MDA following endotoxin injection. In normal rats, endotoxin appears to trigger the liberation of free radicals accelerating depletion of hepatic energy reserves, over and above the effect of decreased hepatic blood flow. In contrast, increased lipid peroxidation was not detected in cirrhotic rats despite GSH and GPX consumption during endotoxemia (indicating oxygen radical generation). Cirrhotic livers were apparently protected against oxygen radical injury by higher levels of endogenous GSH and GPX. Reduced hepatic blood flow may be mainly responsible for the alteration in energy metabolism of the cirrhotic liver. PMID- 8516567 TI - Chylomicron metabolism in experimental cirrhosis and cholestasis. AB - Recently it has been demonstrated that artificial emulsions made of lecithin, cholesterol, cholesteryl-oleate and triolein simulate the metabolism of the natural chylomicra. Artificial-chylomicron delipidation and remnant disappearance from plasma were investigated in rats with carbon tetrachloride-induced hepatic cirrhosis or with cholestasis due to bile-duct ligation. Artificial chylomicra were labelled simultaneously with glyceryl tri [9, 10 (N)-3H] oleate and cholesteryl [1-14C] oleate and injected intra-arterially. Simultaneous chylomicron delipidation and remnant removal by the liver were calculated from the plasma radioactivity decay curves: that of glyceryl tri [9, 10 (N)-3H] oleate signifying the combined delipidation and particle-removal processes, whereas that of cholesteryl [1-14C] oleate representing the particle disappearance rate from plasma. Particle delipidation was increased in cirrhosis and decreased in cholestasis, implying faster and slower lipolysis rates respectively. On the other hand, the remnant removal rate by the liver slowed down in both experimental pathologies. PMID- 8516568 TI - Glucose-dependency of the insulin stimulatory effect of glucagon-like peptide-1 (7-36) amide on the rat pancreas. AB - The glucose-dependent action of GLP-1 (7-36) amide (GLP-1) on insulin secretion was studied in isolated islets and in the perfused rat pancreas. In islet experiments in the presence of non-stimulatory glucose levels (< 3 mmol/l) a GLP 1 concentration of 10 nmol/l increased insulin secretion by 83%. However, higher GLP-1 concentrations (25 and 100 nmol/l) could not further enhance this effect (85 and 83%, respectively). The onset of the stimulatory action of a supramaximal GLP-1-load (25 nmol/l) was at a glucose level of 3 mmol/l. In the perfused pancreas, 25 nmol/l GLP-1 induced a strong insulin release at 5 mmol/l glucose, but under basal glucose (2.8 mmol/l) only a slight enhancement of insulin secretion occurred during the late phase (30 to 54 min) of perfusion (P < 0.05). In conclusion, a slight but not dose-dependent stimulation of insulin secretion by supramaximal GLP-1 loads under basal glucose levels was found. The necessary GLP-1 concentrations to achieve this in vitro effect are beyond physiological or postprandial levels. PMID- 8516569 TI - [Extracellular matrix, adhesion molecules and cytoskeleton of the lung]. PMID- 8516570 TI - [Pathophysiology of myocardial stunning and its clinical significance]. PMID- 8516571 TI - [Effect of long-term oxygen inhalation on prognosis in patient with respiratory insufficiency]. PMID- 8516572 TI - [Assessment of exercise performance by a pedometer in patients with chronic respiratory failure]. PMID- 8516574 TI - [Implantable cardioverter defibrillator]. PMID- 8516575 TI - [Application of simulation system in developing artificial heart]. PMID- 8516573 TI - [Selection of pacing mode (1)]. PMID- 8516576 TI - [Applicability to exercise test of thermodilution technique for right ventricular ejection fraction]. AB - To assess the reliability of right ventricular ejection fraction (RVEF) during exercise measured by thermodilution technique using a modified Swan-Gantz catheter with a fast-response thermister, we measured RVEF under several conditions in 19 patients with cardiac disease. Measurements were repeated 5 times in each condition, and average RVEF and coefficient of variation (CV) were evaluated. 1) Injectate volume did not affect RVEF and CV. 2) A reduction in RVEF occurred with the thermister moved from proximal portion to distal portion within the pulmonary artery. 3) There were no differences in measurements of RVEF and CV between those during spontaneous breathing and those during apnea. 4) Postural change from supine to sitting decreased RVEF (38 +/- 8 to 35 +/- 9%; p < 0.05) and increased CV (7 +/- 2 to 13 +/- 5%). 5) Exercise increased RVEF (35 +/- 9 to 37 +/- 10%; p < 0.05) but did not change CV (13 +/- 5 vs 13 +/- 5%) compared with rest in the sitting position. 6) Cardiac rhythm (sinus vs atrial fibrillation) did not affect CV. 7) Average value of RVEF and CV during exercise were not different among 3, 4, 5 times repeated measurements. We considered that thermodilution technique for RVEF was applicable to exercise test, and 3 measurements were enough to determine the average value of RVEF during exercise. PMID- 8516577 TI - [A study on normal coronary arteriogram by provocation and spontaneous anginal attack: 4 cases of ST elevated angina with normal coronary arteries by provoked and spontaneous attacks]. AB - During 3 years and 5 months, we experienced 3 of 172 cases of provocations on normal coronary arteries which presented ST elevated angina by ergonovine provocations. The incidence was 2.5% and 4% for all ergonovine provocations and intracoronary ergonovine provocations respectively. One case presented spontaneous attack in coronary arteriography, indicating similar state to occur not only with provocation but also in spontaneous attack. Examination of literature revealed no apparent report on such cases as this. For pathogenesis, the possibility of changes of small vessels was suggested in view of various literature and its specificity to the coronary arterial region. PMID- 8516579 TI - [Serum CA125 measurement is useful in 3 cases with pericardial effusion]. AB - Previously we reported that serum CA125 level is elevated in cases of pericardial effusion. We report three cases in which serum CA125 measurement is useful for assessing clinical status. In case 1, a 19-year-old came to our hospital for cardiac tamponade. Moderate degree of pericardial effusion and high CA125 level were observed. After the pericardectomy the serum CA125 level was normalized and pericardial effusion disappeared. Case 2, a 50-year-old man with mesothelioma and in whom serum CA125 level was elevated with pericardial effusion. After cardiac drainage his condition improved, with decreased CA125 level. However, later the CA125 level rose and recurrent localized pericardial effusion with worsening condition was observed. In case 3, in a 78-year-old woman with pericardial effusion no recurrence was observed after pericardial drainage. Her CA125 value was normal. These results indicated that measurement of CA125 value is a useful marker for assessing the clinical course of this disease. PMID- 8516578 TI - [The influence of repetitive delivery of radiofrequency current in catheter ablation]. AB - The single delivery of radiofrequency current to the cardiac tissue can produce discrete small and shallow area of homogeneous coagulation necrosis. Little is known, however, concerning the influence of repetitive deliveries of radiofrequency current to the identical site of the ventricular myocardium. Therefore, in animal experiments using 8 dogs, we investigated the influences of those applications on the ventricular myocardium from the histological and electrocardiographical aspects. The used frequencies of radiofrequency current were 13.56 MHz (RF-50), 520 kHz (Hatt 200 S) and 500 kHz (LL-50). Released power was 25 Watts in current and 20 seconds in duration. The innings of application were 10, 20 and 30 times per one ablation session. The depth of ablated lesion became greater as the applied innings increased in any generator of radiofrequency current. The ablated lesion by the delivery over 20 times reached from the ventricular endocardium to the epicardium. In contrast, surface area produced by repetitive application was determined by the size and length of the tip of electrode catheter. T wave inversion and isolated premature ventricular contraction on electrocardiogram were observed only during repetitive radiofrequency energy application. Thus, since the repetitive delivery of radiofrequency energy to the identical myocardium caused the deep ablated lesion reached to the epicardium, caution should be taken against myocardial perforation in a clinical setting. However, this application could be useful for the ablation of deeper lesion responsible for ventricular tachycardia. PMID- 8516580 TI - [A case of right atrial myxoma: M-mode and pulsed-Doppler echocardiographic findings before and after operation]. AB - There are some reports concerning operations of right atrial myxoma. But precise effect on systemic hemodynamics before and after operation of right atrial myxoma has not been reported. We studied hemodynamics of a 54 year-old male with right atrial myxoma before and after removal of myxoma by M-mode and two-dimensional echocardiography. He was admitted to our hospital because of dyspnea on effort and orthostatic dizziness. On two-dimensional echocardiography the apical four chamber view showed an abnormal huge mass echo with cystic change (6.9 x 4.4 cm) moving between the right atrium and the orifice of tricuspid valve. From this finding emergent operation was undertaken with the possible diagnosis of right atrial myxoma, and the mass was found to be a benign myxoma histopathologically originating from the right side of atrial septum. Left ventricular dimensions (Dd, Ds) and the dimension of left atrial chamber were enlarged after the operation by M-mode echocardiography. Among the left ventricular inflow parameters, rapid filling peak velocity (E) increased with no change in presystolic peak velocity (A) and A/E improved from 1.63 to 0.95. This improvement of left ventricular diastolic function was supposed to be induced through the increased preload. After the operation his manifestations of dyspnea and dizziness have disappeared. It should be emphasized that an increase in preload after the removal of right atrial myxoma is very important to keep left ventricular diastolic and systolic function. PMID- 8516581 TI - [Two cases of acute myocardial infarction with simultaneous occlusions of two main coronary branches]. AB - We report two rare cases of acute myocardial infarction with simultaneous occlusion of two main coronary branches. Case 1 was a 66-year-old man. Emergent CAG demonstrated total occlusions of RCA-segment 1 and LCX-segment 13. The patient underwent a direct PTCA of the RCA occlusion and an intracoronary infusion of urokinase. Angiography before discharge revealed a 25% stenosis of the RCA and a 75% stenosis of the LCX. Case 2 was a 68-year-old man. His ECG showed ST elevation in inferior and anterior leads. Emergent CAG demonstrated a 99% stenosis of RCA-segment 1 and total obstruction in LAD-segment 6. The distal LAD was not visualized by antegrade and retrograde flow from collaterals. We considered the state of hyper-coagulability and reducing of coronary blood flow as the mechanism of simultaneous occlusions in our cases. PMID- 8516582 TI - Anesthesia machine checkout and troubleshooting. PMID- 8516583 TI - Endotracheal tubes and ancillary equipment for intubation. PMID- 8516584 TI - Electronic monitoring equipment. PMID- 8516585 TI - Medical gas delivery systems. PMID- 8516586 TI - The anesthetic machine. PMID- 8516588 TI - Anesthetic breathing systems. PMID- 8516587 TI - Vaporizers used in veterinary anesthesia. PMID- 8516589 TI - Anesthetic pollution and waste anesthetic gas scavenging. AB - The significance of chronic exposure to anesthetic pollution for veterinarians and their associates is not well defined, but one cannot ignore the evidence that a potential occupational health hazard exists. Installation of a scavenging system can reduce anesthetic pollution and personnel exposure to waste gases significantly. However, it is important to realize that these systems are not a replacement for safe anesthetic practices and are only effective when used correctly and maintained properly. PMID- 8516590 TI - Methods for epidemiologic analyses of multiple exposures: a review and comparative study of maximum-likelihood, preliminary-testing, and empirical-Bayes regression. AB - Many epidemiologic investigations are designed to study the effects of multiple exposures. Most of these studies are analysed either by fitting a risk-regression model with all exposures forced in the model, or by using a preliminary-testing algorithm, such as stepwise regression, to produce a smaller model. Research indicates that hierarchical modelling methods can outperform these conventional approaches. I here review these methods and compare two hierarchical methods, empirical-Bayes regression and a variant I call 'semi-Bayes' regression, to full model maximum likelihood and to model reduction by preliminary testing. I then present a simulation study of logistic-regression analysis of weak exposure effects to illustrate the type of accuracy gains one may expect from hierarchical methods. Finally, I compare the performance of the methods in a problem of predicting neonatal mortality rates. Based on the literature to date, I suggest that hierarchical methods should become part of the standard approaches to multiple-exposure studies. PMID- 8516591 TI - Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data? AB - In the context of competing risks the Kaplan-Meier estimator is often unsuitable for summarizing failure time data. We discuss some alternative descriptive methods including marginal probability and conditional probability estimators. Two-sample test statistics are also presented. PMID- 8516592 TI - Sequential monitoring of clinical trials: the role of information and Brownian motion. AB - Sequential monitoring has been a topic of major interest in clinical trials methodology over the past two decades. This paper presents a unified conceptual framework for sequential monitoring that covers a wide variety of monitoring procedures in a wide variety of clinical trial settings. The central elements of this framework consist of a suitable concept of statistical information and a scheme for using this concept as a basis for summarizing the accumulating results of a trial in a standardized form, through a stochastic process that can be shown to approximate classical Brownian motion. The ideas are developed in a simple step-by-step fashion and illustrated by several practical examples. PMID- 8516593 TI - Conditioned life tables from registries with unidentified random losses. AB - We identify two types of random loss that may afflict registries which use 'passive follow-up'. The effects of these errors on estimates related to survival are examined mathematically and numerically. A procedure for correcting the attendant biases is suggested, and its strengths and limitations are explored. PMID- 8516594 TI - Power of testing proportions in small two-sample studies when sample sizes are equal. AB - In planning experiments having two groups of equal but small size, investigators face the uncertainty of power calculations that rely on asymptotic methods. This paper presents a method for determining power for two-sided tests. I compare two randomization tests, Fisher's exact test (FET), and the mid-P (MID), with the uncorrected chi-square test (CHI). Results show power as a function of relative risk for these methods, and assesses their relative power and type I error rates. MID is shown to have intermediate power between CHI, which is the most powerful, and FET, the least powerful. Situations are shown in which CHI and MID occasionally exceed the nominal level of alpha. PMID- 8516595 TI - The application of developments in theoretical biostatistics to epidemiologic research. PMID- 8516596 TI - Sir Austin Bradford Hill, 1897-1991. PMID- 8516597 TI - Advances in melanoma treatment and research. Proceedings of the 4th annual melanoma conference. Tampa, Florida, September 3-6, 1992. PMID- 8516598 TI - Epidemiology of malignant melanoma, worldwide incidence, and etiologic factors. AB - Malignant melanoma is increasing at an alarming rate, exceeding that of any other cancer in the United States today. Genetic susceptibility and exposure to ultraviolet radiation are thought to be the two most important risk factors for development of the neoplasm. While genetic factors cannot be altered, minimizing exposure to ultraviolet light, especially intermittent intense type, and photoprotective measures may significantly reduce the development of this ominous cutaneous malignancy. PMID- 8516599 TI - Malignant melanoma: differential diagnosis of the pigmented lesion. AB - Familiarity with the clinical signs of malignant melanoma can result in earlier recognition and thus potentially decrease both patient morbidity and mortality. Unfortunately, several cutaneous tumors, both benign and malignant, have clinical similarities to this neoplasm, often making the correct diagnosis difficult. The purpose of this paper is to discuss the clinical characteristics of the different types of malignant melanoma and those lesions that mimic this ominous malignancy. Furthermore, diagnostic clues to help delineate between these various pigmented lesions are provided. PMID- 8516600 TI - Prevention and early detection of melanoma: a surgeon's perspective. AB - Americans are clearly losing the battle against malignant melanoma. In 1930, it was estimated that one in 1,500 people would develop melanoma sometime during their lifetimes, but by the year 2000, one in 75 people in the United States will develop the disease. Although the individual case prognosis is improving, the death rate has doubled in the last 35 years. The rising mortality rate has to be attributed to an escalating incidence that is not offset sufficiently by improved diagnosis and treatment. Malignant melanoma is a disease that lends itself to early detection and screening programs. Melanoma is highly prevalent and causes considerable morbidity and mortality. The natural history of the disease is known and it is well established that the earlier diagnosis of "thinner" lesions can reduce morbidity and mortality. There is also an acceptable, safe, inexpensive, and noninvasive screening test for melanoma, the skin examination. This work reviews the current evidence that melanoma screening may be effective, compares screening projects for this cutaneous tumor with other screening programs, and outlines a proposed project for melanoma screening. PMID- 8516601 TI - Melanoma mimicking dermal and Spitz's nevus ("nevoid" melanoma). AB - We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma. PMID- 8516602 TI - Diagnosis and management of early melanoma: a consensus view. AB - The inefficacy of treatments for advanced melanoma have shifted the focus toward the recognition of early melanoma which is associated with a much more favorable outcome. In January 1992 the National Institutes of Health (NIH) held a Consensus Conference to establish definitions and therapeutic recommendations for the management of early melanoma. Early melanoma was defined as either in situ or invasive melanoma < 1 mm in depth. Surgical margins of 0.5 cm for in situ melanoma and 1 cm for invasive melanoma < or = 1 mm thick were recommended. The pathology reports should include as a minimum the diagnosis of melanoma, the maximum tumor thickness, and the status of the margins. Elective nodal dissection as well as high-tech radiologic procedures were not recommended. Follow-up of patients for the development of second primaries and of family members who may be at increased risk for melanoma was also recommended. Public education programs were suggested to inform the public of the increasing melanoma risk and improved survival through early detection. PMID- 8516603 TI - Digital epiluminescence microscopy in the evaluation of pigmented lesions: a brief review. AB - Epiluminescence microscopy (ELM) is the application of oil followed by compression by a transparent material and examination under tangential illumination with magnification. This technique reduces the reflected light from the irregular surface of the stratum corneum and makes the epidermis more transparent so that structures at the dermal epidermal junction and upper dermis may be visualized. Digital ELM is the capture of ELM images by a television camera attached to a computer. The ELM approach results in improved diagnostic accuracy for pigmented lesions in the order of 20%. Advantages of digital ELM over standard ELM are the ability to capture images in an almost endless array of colors and hues, permanence of recording without degradation over time, the ability to transmit information electronically over long distances, and the ability to enhance certain features through electronic manipulation. Among the potential applications of digital ELM are assistance in establishing the diagnosis of melanoma during screening, maintenance and retrieval of images in patients who are being followed clinically with pigmented lesions, and better understanding of clinical histopathologic correlations. PMID- 8516604 TI - Histopathologic study of recurrent Clark level II melanomas. AB - Overall, the prognosis for thin lesions of melanoma (less than 0.76 mm) is excellent. However, a number of melanoma patients with seemingly innocuous lesions have been reported to develop recurrences. For this reason, we examined histologic sections taken from eight cases of Clark level II melanoma that unexpectedly recurred, and compared their histopathologic features with an equal number of nonrecurrent lesions in whom reliable clinical follow-up data were available. Prognostic variables including Breslow thickness, mitotic rate, ulceration, the presence or absence of regression, a vertical growth phase component, and an associated banal nevus were evaluated in a double blind manner. When attempts were made to predict outcome based on one or more prognostic variables, the only correlation of statistical significance was the Breslow thickness (P = 0.04). A Breslow thickness greater than 0.4 mm was associated with a significantly shorter disease free interval than a thickness below 0.4 mm. There was no significant correlation between predicted outcome based on the histologic features examined and the eventual outcome based on history of recurrence (P = 0.36). These data indicate that although prognostic models that predict outcome in melanoma are generally reliable, there is a sizable population of patients with thin melanomas that do worse than would be expected. PMID- 8516605 TI - Computer database for melanoma: a clinical management and research tool to ensure continuous quality assessment. AB - The need for an efficient method to handle data and for chart documentation is more apparent today than at any time in the past. High volume clinics for screening, diagnosis, and treatment are the rule rather than the exception in modern practice. A papermill medical record department or tumor registry fails on a day-to-day basis because of inefficiency of data collection, filing, storage, and abstraction. Requirements of the Joint Commission for the Accreditation of Health Care Organizations (JCAHO) include the setting of standards and the ability to query data to ensure the standards are met. A PC-based software program has been developed with the following features: (1) ongoing timed queries of the data are possible on any variable collected in the database to monitor trends in the standards established for care in the clinic; (2) a daily update of the database is performed so that it may be used as a clinical management tool, acting as an electronic medical record or as a clinical research tool; (3) the software will summarize the chart by abstracting a predetermined list of key data elements to improve clinical efficiency; (4) chart documentation is improved for Medicare coding requirements to maximize physician reimbursement; and (5) clinic notes and referral letters are generated the same day as the clinic visit to allow patients to have a copy of their clinic notes or for same day FAXing to the referring doctors. To date, > 1,200 patients with melanoma have been registered and entered into the system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516606 TI - Treatment of the primary malignant melanoma: a review. AB - Treatment of the primary tumor in malignant melanoma includes a surgical excision of the surrounding skin and subcutaneous fat to remove tumor and occult focci. The most significant factor in predicting recurrence of melanoma at the primary tumor site is thickness of the primary tumor and the presence of ulceration. The margin of resection for lesions less than .76 mm is 1 cm and the margin of resection for lesions .76 mm or greater is 2 cm. However, we must remember that an additional margin of skin resection rarely compromises a satisfactory esthetic result and prognosis may be gravely affected by local recurrence of the tumor. The primary incisions may require special considerations if the underlying lymph nodes are also to be resected. On the face less margins may be advantageous for an optimal cosmetic result. The method of reconstruction depends upon the location and size of the defect, the functional and esthetic requirements of the patient, and the medical condition of the patient. Reconstructive methods with primary closure, split thickness skin grafts, full thickness skin grafts, local flaps, and regional flaps are discussed for different locations. PMID- 8516607 TI - Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. AB - The percentage of melanoma patients diagnosed at an early stage is increasing. Many of these patients, particularly those with primary tumors thicker than 1.5 mm, harbor occult metastases in regional nodes and are eligible for regional lymphadenectomy as part of their primary management. Until the results of recently completed prospective randomized trials are available the role for elective lymphadenectomy in terms of survival benefit remains a controversial issue. A new technique, intraoperative lymphatic mapping and sentinel node biopsy, has emerged as a simple way to determine whether or not metastatic disease is present. An intradermal injection of a vital blue dye at the site of the primary tumor allows identification of a "sentinel" node in the regional basin. A study of 237 patients was recently reported by Morton et al. (Arch Surg 127:392-399, 1992; Surg Oncol Clin North Am 1:247-259, 1992) demonstrating that the sentinel node can be readily identified > 80% of the time and that histologic examination of the node results in at least a 95% accuracy rate in staging the nodal basin for metastases. Our present series substantiates the results of the original study. An international multicenter trial has been proposed to further confirm the accuracy and universal feasibility of this technique. Acceptance of this technique will lead to a selective approach to regional lymphadenectomy, as only patients with proven micrometastases will undergo lymph node dissections. This approach should satisfy both the advocates and the opponents of elective regional lymphadenectomy. PMID- 8516608 TI - Identification of lymphatic drainage basins in patients with cutaneous melanoma. AB - Lymphoscintigraphy has been shown to be of assistance in predicting lymphatic basins at risk for the development of metastatic disease in patients with cutaneous malignant melanoma. To further establish the efficacy of this method, 212 patients presenting to the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida with primary melanoma of the head, neck, and trunk have been studied. All patients had clinical stage 1 or 2 melanoma and were candidates for elective lymph node dissection. Drainage patterns identified by lymphoscintigraphy were compared to those predicted by historical anatomical guidelines and were found to be discordant in 63% of patients with tumors of the head and neck, and in 32% of those with primary lesions located on the trunk. Operative intervention was changed because of these findings in 47% of all patients, with 19% undergoing dissection of nonclassical lymph node basins. An additional 28% did not have a node dissection because of failure of the scintigram to demonstrate a predominant drainage basin or the demonstration of multiple drainage sites. After a mean follow-up of 2.8 years, there have been no recurrences in basins not positive by lymphoscintigraphy. The lymphatic drainage from cutaneous melanoma of the head, neck, and trunk cannot be reliably predicted by clinical judgment or classic anatomic guidelines, and lymphoscintigraphy is indicated in these patients prior to elective lymph node dissection. PMID- 8516609 TI - Malignant melanoma and the prognostic implications of pregnancy, oral contraceptives, and exogenous hormones. AB - The co-existence of melanoma and pregnancy present unique questions about patient management. There have been conflicting reports over the past several decades about the implications to melanoma of pregnancy and reproductive hormones. Several recent studies, have, however, produced a reasonable consensus. PMID- 8516610 TI - Radiologic imaging in malignant melanoma: a review. AB - The role of imaging in the staging of malignant melanoma is reviewed. Computed tomography (CT) and magnetic resonance (MR) are useful for detecting liver, lung, and central nervous system (CNS) metastases in asymptomatic patients at high risk and in symptomatic patients. Plain films, bone scan, and gastrointestinal (GI) studies are useful in patients with skeletal or GI complaints. Additionally, imaging studies have a primary role for ascertaining the response, if any, to treatment. PMID- 8516611 TI - Role of surgery for metastatic malignant melanoma: a review. AB - The role of surgery in the management of metastatic melanoma is reviewed. Favorable prognostic factors include a longer disease free interval, single site of disease, complete resection, and nonvisceral metastases. Patients undergoing complete resection of remote nonvisceral metastases have a median survival of 17 50 months, and a 5-year survival (5YS) of 9-35%. Patients with pulmonary metastases are usually asymptomatic; complete resection results in a median survival of 8-20 months, and a 5YS of 10-25%. In contrast, patients with metastases to brain or gastrointestinal tract are usually symptomatic; resection offers good palliation, but their median survival is only 7-10 months with few long-term survivors. The key to effective surgical management of patients with metastatic melanoma is careful patient selection. PMID- 8516612 TI - Role of radiotherapy in the primary management of mucosal melanoma of the head and neck. AB - Historically, radiotherapy has played a very small role in the management of mucosal melanoma, largely because the disease has been characterized as radioresistant. Recent observations regarding the radiobiology and clinical response of cutaneous melanoma have prompted investigators to reevaluate the role of radiotherapy in mucosal melanoma. A series of reports published during the last decade using radiotherapy alone have documented complete response rates of 50-75% with durable long-term control in half to two thirds of the complete responders. These data, taken in conjunction with the high rate of local failure after surgery alone, suggest that radiotherapy would have a useful role as a surgical adjuvant in a combined modality approach, as well as being of value in the primary management of unresectable disease. Guidelines for management based on the available data are presented. PMID- 8516613 TI - Chemotherapy for stage 4 melanoma: a three-year experience with cisplatin, DTIC, BCNU, and tamoxifen. AB - The management of metastatic melanoma has been frustrating from a clinician's point of view because of the relative unresponsiveness of the tumor to chemotherapy and the infrequency of clinically useful objective responses. Although no single agent can be recommended at this time, old standard drugs used in new combinations, immunomodulators, and systematic approaches to dose intensification have created more interest in the chemotherapy of melanoma. Forty seven consecutive patients with Stage 4 melanoma with measurable disease were treated with combination chemotherapy, consisting of DTIC, BCNU, cisplatin, and tamoxifen. The cycle was repeated every 4 weeks and a total of 6 cycles were delivered. Patients were then restaged to assess the response. Nine patients who were registered during the same time period with Stage 4 disease and elected not to be treated served as the control population. Seventeen patients (46%) achieved a clinical response with six patients (12.7%) undergoing a complete response. The overall survival of all Stage 4 patients in the series was 18% at 3 years. There were significant differences noted in those patients who were treated and the no treatment controls (p = 0.004) and for those patients that received an objective response vs those that progressed on the protocol (p < 0.0001). It is recommended that all patients with Stage 4 melanoma be treated on protocol and results of other trials of systemic therapy for metastatic melanoma be compared to this cisplatin-based regimen instead of a no-treatment arm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516614 TI - Molecular basis of tumor progression: mechanisms of organ-specific tumor metastasis. AB - Tumor cell metastasis is an extremely complex process governed by many different classes of molecules with each class having a separate function. Metastasis is the result of multiple sequential steps and is a highly organized, nonrandom, and organ-selective process. Recent advances in tumor and molecular biology have permitted the identification of a variety of heterogeneous molecules governing invasion (degradative enzymes, motility factors), adhesion (integrins, selectins, cadherins, immunoglobulin-like superfamily, annexins), and growth (paracrine and autocrine growth factors) of tumor cells. This diverse group of biological molecules is collectively responsible for determining whether tumor cells can progress from a single malignant cell to a lethal, multiorgan, metastatic disease. PMID- 8516615 TI - Interim results of a phase II multicenter clinical trial evaluating the activity of a therapeutic allogeneic melanoma vaccine (theraccine) in the treatment of disseminated malignant melanoma. AB - A total of 139 patients with disseminated malignant melanoma were enrolled in an uncontrolled Phase II trial evaluating the activity of Melacine, allogeneic vaccine incorporating Detox, immunologic adjuvant. Nineteen patients, including 18 with progressive disease, dropped out of the study prior to receiving one full vaccination course of five injections over 6 weeks. Disease presentation among study participants included skin or lymph nodes (34%), pulmonary (24%), visceral (34%), and no evidence of disease (NED) (7%). One documented metastatic site was seen in 41%, two sites in 24%, and three or more sites in 27% of the patients studied. Objective clinical response rates for evaluable patients were CR 3%, PR 5%, minor response 4%, stable 23%, and progressive disease 65%. Median survival from time of diagnosis for patients treated with Melacine is presently estimated at 23 months (45/139 patients censored). Median date from diagnosis of metastatic disease to study entry was 3 months. Side effects were generally mild to moderate with pain at injection site (37%), granulomas (13%), erythema (6%), and flu-like symptoms (14-29%) predominating. Precursor antimelanoma cytotoxic T cell (pre CTL) titers, in comparison with prestudy evaluations, clearly increased in 42% of the patients evaluated. Significantly extended survival characteristics were observed among patients who displayed an expansion of a population of CD57, CD8 co-positive lymphocytes during therapy in comparison with those patients not displaying this peripheral blood lymphocyte (PBL) population expansion (34 mo vs. 12 mo, respectively, p = 0.04) and among those patients displaying disease stabilization or better as a clinical response (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516616 TI - Possibilities of immunotherapy and gene therapy for malignant melanoma. AB - Over the last decade, both immunotherapy and gene therapy have emerged as exciting new modalities in the treatment of malignant melanoma. The fact that many melanoma patients mount cellular and humoral responses against their tumors, and that melanomas express both HLA antigens and tumor-associated antigens (TAA), has led to an increased interest in the treatment of melanoma by manipulation of the immune system. Advances have occurred in several areas, including a) the use of monoclonal antibodies, alone or in combination with cytokines, b) tumor vaccines, using whole cell preparations or cloned melanoma antigens, c) adoptive immunotherapy, with tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs), and d) gene therapy, designed to increase the immunogenicity of the tumor, increase the effectiveness of the TILs, or alter the basic mechanisms of tumor cell growth and regulation. Some of the advances in these areas are discussed. PMID- 8516618 TI - Identification of submicroscopic lymph node metastases in patients with malignant melanoma. AB - In order to detect micrometastatic disease, our laboratory has developed a method for evaluating lymph node sections from patients with stage 1 or 2 melanoma. Lymph nodes isolated from standard dissections are bivalved; one half is subjected to routine histopathological evaluation and the other half disrupted and placed into cell culture. The cultured cells are identified by cytologic examination, immunohistologic staining, and the presence of melanoma-associated antigens. Lymph nodes (448) from 62 patients with malignant melanoma were evaluated by tissue culture. Fifteen patients were upgraded from stage 1 or 2 to stage 3 disease after micrometastases were identified in lymph node cultures. Recurrence of disease in histologically node negative patients, during a mean 24 month follow-up, has only been observed thus far in patients with culture positive lymph nodes. In addition, these results add evidence to the belief that missed micrometastatic disease in regional nodes is a sign of occult systemic metastases that would account for the defined recurrence rate in histologically node negative patients. PMID- 8516617 TI - Development of serotonin antagonists for the control of chemotherapy-induced emesis. AB - Chemotherapy-induced emesis is one of the most common and severe side effects of systemic cancer therapy. During the 1980s, the development of metoclopramide based combination antiemetic regimens resulted in complete or near-complete control of emesis in 60-70% of patients receiving cisplatin-based chemotherapy. However, 30-40% of patients remained poorly controlled with these regimens, and bothersome side effects such as extrapyramidal symptoms and sedation hindered therapy in some patients. The selective 5-hydroxytryptamine (serotonin) inhibitors are a new class of antiemetics that have further improved the control of chemotherapy-related nausea and vomiting. Ondansetron, the first of these compounds available commercially, has proven superior to high-dose metoclopramide in controlling cisplatin-induced emesis. In addition, no extrapyramidal side effects have been observed with ondansetron. Although the currently approved dosing schedule for ondansetron is 0.15 mg/kg intravenously (IV) every 4 hours for three doses, recent data indicate that a single 32 mg dose prior to chemotherapy may be superior. The addition of dexamethasone (10-20 mg IV prior to chemotherapy) improves the efficiency of ondansetron; this combination should be considered in all patients receiving cisplatin-based chemotherapy. The role of ondansetron in non-cisplatin chemotherapy is not completely defined, but patients unresponsive to other antiemetic therapy often have improved control with the addition of ondansetron. PMID- 8516619 TI - Intrasynovial levels of sulphated glycosaminoglycans and autoantibodies to type II collagen in rheumatoid arthritis: a correlative analysis. AB - It is uncertain whether the autoantibodies to type II collagen that occur frequently in the serum and synovial fluid of patients with rheumatoid arthritis (RA), but rarely in other articular diseases, are primary or secondary to cartilage damage. Hence, we measured antibodies in synovial fluid from patients with RA and other articular diseases and related these to the concentration of sulphated glycosaminoglycans, as a measure of ongoing cartilage catabolism. Synovial fluids from 42 patients with RA and 30 patients with other articular diseases were studied. We found that levels of antibodies to native and denatured collagen were significantly higher in RA than in all other articular diseases, whereas concentrations of sulphated glycosaminoglycans were similar. The absence of any correlation between levels of sulphated glycosaminoglycans and antibodies to collagen weighs against the occurrence of such antibodies in RA as a secondary effect of cartilage damage. PMID- 8516620 TI - Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate. AB - We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP liposomes 7 days earlier prevented inflammation as compared to controls. PMID- 8516622 TI - Viewpoint: time for change in pediatric rheumatology. PMID- 8516621 TI - Widespread vasculopathy with hemolytic uremic syndrome, perimyocarditis and cystic pancreatitis in a young woman with mixed connective tissue disease. Case report and review of the literature. AB - A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy with high steroid doses, a cyclophosphamide pulse and 4 weeks of plasmaphresis with plasma exchange improved the heart, but not the renal condition. Symptomatic pancreatitis became the dominant problem of a progressively consuming process that resulted in the death of the patient. Post-mortem examination revealed widespread vasculopathy with intima proliferation and only minimal fibrosis involving the kidneys, heart and other main organs, including the pancreas. Taken together, the clinical picture was of an overlap between scleroderma and systemic lupus erythemathosus; the serologic and histopathologic findings suggest a diagnosis of a severe form of mixed connective tissue disease (MCTD). PMID- 8516623 TI - Bioavailability of oral chondroitin sulfate. PMID- 8516624 TI - Leukaemia inhibitory factor stimulates proteoglycan resorption in porcine articular cartilage. AB - Leukaemia inhibitory factor (LIF) is a secretory glycoprotein produced by tumour, mesenchymal and haemopoietic cells. LIF has been found to have pleiotropic actions that include the capacity to regulate cell differentiation, promote acute phase protein synthesis and stimulate calcium release in bone explants. In view of its similarity to other cytokines that affect cartilage metabolism, the effects of LIF on proteoglycan resorption were examined in pig cartilage explants. Endotoxin-free recombinant mouse LIF was found to produce a dose dependent increase in sulphated glycosaminoglycan (S-GAG) release (ED50 = 123 U/ml, approx. 25-50 pM). Statistically significant stimulation was observed with doses of 100 U/ml or greater. When pig cartilage was stimulated with maximum concentrations of LIF and either interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha), in each case a significantly greater release of S-GAGs was observed than with the respective cytokines alone (P < 0.05). Comparison of the areas under the curves showed that the action of LIF was additive, and not synergistic with other catabolic cytokines. Dose-response studies showed that transforming growth factor beta (TGF beta) produced a partial inhibition of LIF-stimulated release of S-GAGs (ED50 = 4.5 U/ml). Statistically significant inhibition was observed with doses of 2 U/ml or greater. These results showed that LIF stimulated proteoglycan resorption in vitro and that this effect was modulated by other cytokines. Whether LIF contributes to the progressive destruction of cartilage in septic or chronic inflammatory arthritis remains to be determined. PMID- 8516625 TI - Thyroid disorders in Chinese patients with systemic lupus erythematosus. AB - To clarify the prevalence of thyroid disorders in Chinese patients with systemic lupus erythematosus (SLE), 45 SLE patients not receiving corticosteroid therapy for at least 6 months were selected over a period of 1 year. They were investigated by utilizing thyroid ultrasonography and by determinations of thyroid antibodies and thyroid function. Of these patients, 24 (53.3%) showed abnormal sonographic findings. Thyroid antibodies (microsomal and/or thyroglobulin) were detected in 21 patients (46.7%), but a low index of thyrotropin-binding inhibitory immunoglobulin (TBII) was found in only one euthyroid patients with a normal echogram. Ten patients (22.2%) had abnormal thyroid function. The mean disease duration was longer in patients with thyroid anomalies (p < 0.05). Hashimoto's thyroiditis was found in four patients (8.8%), two of whom had hypothyroidism. We concluded that thyroid anomalies are frequently found in patients with SLE in the area of this study. The possibility of the coexistence of thyroid disorders in systemic lupus erythematosus should be carefully considered throughout the course of patients' follow-up, especially in those with a long disease duration. PMID- 8516626 TI - Detection of antibodies to a 70 kDa Plasmodium falciparum exoantigen in malarious subjects using synthetic peptides. AB - Indirect fluorescent antibody (IFA) tests and enzyme-linked immunosorbent assays (ELISA) were used to measure antibodies to Plasmodium falciparum in patients with acute malaria from Bolivar State, Venezuela. Antibody titers increased significantly with repeated malarial episodes. IgG antibody responses to 4 synthetic peptides (termed C2, C3, C5, C10) derived from a 70 kDa P. falciparum (Indochina I/CDC strain) exoantigen were evaluated by a peptide-ELISA with overall positivity rates of 20%, 40%, 20% and 58%, respectively. Seropositivity to peptide C10 was consistently over 50% (range 53-75%) among patients of different ages. Overall IgM reactivity to the respective peptides was 53%, 30%, 83% and 70%. IgM reactivity was generally greater in patients with primary malarial infections. The ELISA is a useful adjunct to the IFA in measuring naturally-occurring antibodies to specific parasite proteins. PMID- 8516627 TI - De novo purine biosynthesis in a free living protozoan parasite, Acanthamoeba polyphaga [correction of polypha]. AB - A free living protozoon, Acanthamoeba polyphaga 435/89, was shown to utilize radiolabelled formate and glycine as precursors for purine biosynthesis and to grow in medium devoid of any source of preformed purine compounds. The organism also incorporated into its nucleic acids radiolabel derived from adenosine and guanosine indicating presence of purine salvage pathway. Thus, the presence in A. polyphaga 435/89 of active de novo purine biosynthesis in addition to a purine salvage pathway may be a general characteristics of free-living protozoan organisms since parasitic protozoans are devoid of de novo purine biosynthesis. PMID- 8516628 TI - Defecation by Anopheles arabiensis mosquitoes of host blood infected with live Trypanosoma congolense. AB - Female Anopheles arabiensis mosquitoes were experimentally fed on hamsters and BALB/c mice which were either clean or infected with Trypanosoma congolense. The mosquitoes readily fed on either animal. A blood repletion rate of 82.7% was recorded for mosquitoes feeding on hamsters. Seventy seven per cent of the replete mosquitoes continued to feed while at the same time defecating the host's blood in droplets, ejected in quick succession from the anus. Ninety five per cent of mosquitoes defecating blood while feeding on mice infected with T. congolense ejected live parasites along with the blood. Clean mice inoculated intraperitoneally with T. congolense via tail or defecated blood developed parasitaemia between the third and seventh day. This phenomenon could imply possible mechanical transmission of the parasites to the hosts being fed on by the mosquitoes. PMID- 8516630 TI - Spiroarsoranes of second generation: evaluation of trypanocidal properties against Trypanosoma brucei brucei. AB - The spiroarsoranes are a series of pentavalent arsenicals having interesting trypanocidal properties. They are less toxic than trivalent arsenicals but their activity appear at higher doses and concentrations. The structure-activity relationships study from the first series led to a new generation of spiroarsoranes which has been synthesized and evaluated in vitro and in vivo against Trypanosoma brucei brucei bloodstream forms. Among 40 compounds, 5 were active in vitro at concentrations less than 10 mumol/l and 7 were active in vivo. The most interesting compound of this series (compound I e 2) showed an in vitro activity at 125 mumol/l after 24 hours incubation time and in vivo all the mice were cured after a subcutaneous treatment at 600 mumol/kg in one single dose. The spiranization and the substitution of para-arsanilic acid allowed to obtain a better mean survival time at 300 mumol/kg comparatively to para-arsanilic acid itself used as reference compound. Nevertheless, this second generation of compounds was less active than the selected compound of the first series which was efficient at 150 mumol/kg in subcutaneously one single dose. PMID- 8516629 TI - Class-specific antibody response in rabbits experimentally infected with Trypanosoma evansi. AB - The antibody response to Trypanosoma evansi antigens in rabbits experimentally infected with T. evansi was monitored by SDS-PAGE and "Western" blotting. As defined by the number of antigenic components recognised and the intensity with which they were labelled, responses were predominantly IgG, followed by IgM and IgA. During infection and subsequent drug treatment seven major antigenic components (94, 85, 75.5, 67, 60.5, 43, and 28.6 kDa) were identified by IgG. Antibodies to a 32.4 kDa and three other components (30, 28.6 and 12.5 kDa) appeared during infection and after chemotherapy respectively. Three components (94, 67 and 60.5 kDa) recognised by IgG were also detected by IgM and IgA. Furthermore, two bands (30 and 12.5 kDa) were identified by IgM and one (12.5 kDa) by IgA only after drug treatment, while a 28.6 kDa component was recognised by IgM and IgA during the same period. These findings constitute a basis for the exploration of class-specific antibody responses to T. evansi antigens with relevance to diagnosis, protection and pathology. PMID- 8516631 TI - Comparative analysis of the clinicopathological features in cutaneous leishmaniasis and lupus vulgaris in Turkey. AB - Cutaneous leishmaniasis (LC) and lupus vulgaris (LV) are commonly encountered in the Mediterranean region of Turkey. Differential diagnosis is rather difficult and unreliable purely on clinical grounds; thus histopathological examination is required. Microscopical findings of both lesions may also present some similarities. 12 LC and 16 LV cases were analysed comparatively regarding the clinicopathological features. In the early stage of LC, macrophage granulomas containing numerous leishmania parasites was the key microscopic finding. In the late stage of LC, granulomas consisted of epithelioid histiocytes with scanty organisms were present. LV biopsies showed tuberculoid granulomas with Langhans type giant cells in all cases, and acid fast bacilli were detected only in two cases. PMID- 8516632 TI - Skin changes in filarial and non-filarial lymphoedema of the lower extremities. AB - The pathogenesis of lymphoedema in patients infected with Wuchereria bancrofti or Brugia malayi remains unclear. Lymph stasis and local immunological reactions seem to play the main role. In order to discriminate between the obstructive and immunological effects of the parasite, a comparative histological study of skin specimens obtained from two groups of patients, one with filarial and the other with postsurgical lymphedema of lower extremities, was performed. In both groups patients suffered lymph stasis, in the first due to filariasis, in the other due to removal or irradiation of pelvic lymph nodes. The patients with filarial infection showed hyperproliferation of keratinocytes, focal acantholysis, accumulation of lymphocytes at the epidermo-dermal junction, profuse pericapillary and perivenular mononuclear infiltrations in the dermis marginated granulocytes in capillaries and, in some cases, subepidermal granulocytic infiltrates. There were many dilated initial lymphatics and lymphatic "lakes" between thick collagen fibre bundles. Monoclonal antibody analysis revealed that the most common cells in the infiltrates were macrophages (CD68+). All mononuclear and endothelial cells were HLA-DR+. In contrast, the skin specimens of non-filarial patients revealed only moderate proliferation of keratinocytes, increased numbers of CD1+ epidermal Langerhans cells, moderate pericapillary infiltrates of CD68+, CD4+ and CD8+ cells, and evidently less intensive marking of cells with anti-HLA-DR antibody. There were few initial lymphatics visible. These findings indicate that filarial lymphoedema is complicated by a severe inflammatory component, which is much less expressed in postsurgical lymph stasis. PMID- 8516633 TI - A comparison of the Og4C3 antigen capture ELISA, the Knott test, an IgG4 assay and clinical signs, in the diagnosis of Bancroftian filariasis. AB - To compare methods for diagnosing Bancroftian filariasis, six hundred and seventy four people from rural areas of Papua New Guinea were screened using microfilaraemia, the Og4C3 antigen capture ELISA, an ELISA to detect IgG4 specific antibodies and clinical examination. Both ELISA tests detected around twice the number of positive cases than those detected by the presence of microfilariae alone. No correlation was found with clinical signs and laboratory tests. This study raises concern over the underestimation of the prevalence of filariasis due to ineffective diagnostic criteria. The two ELISA tests should be of value in epidemiological surveys and for monitoring filariasis control programs. PMID- 8516634 TI - Mansonella ozzardi: the course of patency in experimentally-infected patas monkeys. AB - Twenty-five of 30 patas monkeys (Erythrocebus patas) inoculated with varying numbers (35 to 135) of third-stage larvae of Mansonella ozzardi developed patent infections in an average of 163 days. There was no correlation between the size of the inoculum and the length of the prepatent period. Ten of the monkeys were monitored thereafter by regular blood examination for extended periods of time in order to characterize the onset, course and duration of patency. Typically, with the onset of patency, microfilaremias increased steadily, peaking at about 20 weeks and then decreased slowly stabilizing at low levels for up to 48 weeks. Thereafter microfilariae disappeared from the blood and occasionally reappeared in scanty numbers. Laparotomies and followup studies indicated that the spleen was involved in the suppression of peripheral microfilaremia as had been observed earlier in patas monkeys infected with Loa loa. In ten monkeys splenectomized after the initial "wave" of microfilaremia, it was observed that (a) 30% of the animals remained amicrofilaremic, (b) another 30% reestablished patent infections but microfilaremias were lower than presplenectomy levels, and (c) in the remaining 40%, levels of microfilaremia equaled or exceeded pre-splenectomy levels. Patent infections persisted for up to 212 weeks. One monkey splenectomized prior to inoculation with 87 larvae developed a patent infection with microfilaremia which persisted for 156 weeks. Three monkeys with low and high levels of microfilaremia bled at four hour intervals over a 28 hour period showed no evidence of periodicity in the microfilaria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8516635 TI - Reversal of chloroquine resistance in Plasmodium falciparum by CDR 87/209 and analogues. AB - The spreading of resistance towards chloroquine has diminished its value as a potent and safe drug in malaria endemic areas. Recent reports on the reversal of chloroquine resistance in the malaria parasite Plasmodium falciparum in vitro and in vivo by verapamil, desipramine and other Ca(2+)-channel blockers and antidepressants has initiated a strategy for chemotherapy by treatment with chloroquine in combination with a drug resistance modulator. Described here is a class of modulators of distinct structure which reverse chloroquine resistance in a different manner. Contrary to verapamil and desipramine, CDRI 87/209, the most potent compound of this new class and used as a chemical lead, did not restore chloroquine accumulation in the resistant parasites, thereby indicating that besides the proposed blockade of drug efflux other mechanisms are vulnerable targets for a chemotherapeutic approach towards drug resistance. Similar to the former modulators, CDRI 87/209 showed only weak intrinsic plasmodicidal activity and the increase of drug susceptibility was restricted to resistant plasmodia. PMID- 8516636 TI - Pattern of malaria imported by foreign residents under active survey. AB - An active of imported malaria was carried out on 1432 foreign residents entering Czechoslovakia between 1986-1989. The survey group consisted of adult aged 18-35 years who arrived from malaria endemic regions. Of 660 people surveyed who were from regions of Africa south of the Sahara, 10% were positive for Plasmodium falciparum. Whereas, those arriving from South East Asia had a relatively low prevalence of malaria (2.6%), predominantly P. vivax. Of the 10% of cases testing positive for P. falciparum, 85% had less than 10,000 asexual stages/microliters of blood and 75% were asymptomatic carriers. By contrast, 93.8% of P. vivax/ovale infections were diagnosed because of the onset of symptoms. Both the frequency of seropositivity and the geometrical mean reciprocal titre (IgG), using P. falciparum antigen, were higher in those people arriving from Africa (79% and 1,307) compared with those arriving from S.E. Asia (44.4% and 628). Malaria was confirmed, by blood smear examination, in only 23.8% of the seropositive cohort. There was a positive correlation between the percentage of P. falciparum-positive blood smears and the level of antibody titre. There was no correlation between serum reactivity and level of parasitaemia. PMID- 8516637 TI - PCR mediated cDNA synthesis from minute amounts of filarial L3 RNA. PMID- 8516638 TI - The household costs of malaria in Nepal. AB - This paper presents the results of a survey of the costs of malaria falling on households in 6 Nepali districts. Information is presented on the age and sex distribution of cases, use made of sources of treatment other than those offered by malaria control agencies, expenditure on these treatment sources, and days of work and school lost. It is found that adults are more likely than children to be affected by malaria; that 47-77% of patients consult alternative sources of treatment, sometimes spending quite large sums; and that 6-14 days of work and 4 14 days of school were lost on average, the precise figure varying considerably by district and strongly influenced by species of parasite and delay before obtaining treatment from malaria control agencies. The question of the value of lost time is deliberately not addressed, since this requires detailed information on how the household responds to the illness of one of its members. PMID- 8516639 TI - A nurse/author in early menopause reaches out. PMID- 8516640 TI - Pregnant women should keep out of hot tubs. PMID- 8516641 TI - Problem with a staff member? Try these tools. PMID- 8516642 TI - OTC interactions. Vitamins and minerals. PMID- 8516643 TI - Get your patient moving. PMID- 8516644 TI - Birth: nursing's role in today's choices. PMID- 8516645 TI - A picture-perfect birth. PMID- 8516646 TI - B-G-T-E-S-T: a basic review. PMID- 8516648 TI - Risks and rewards of kidney transplant. PMID- 8516647 TI - Third-degree heart block. PMID- 8516649 TI - Rx: error-free meds. PMID- 8516650 TI - What diet can do to combat HIV infection. PMID- 8516651 TI - What are we about? PMID- 8516652 TI - A double-blind fluoroscopic study of cisapride on gastrointestinal motility in patients with functional dyspepsia. AB - Twenty patients with functional dyspepsia were referred for radiologic examination and, upon confirmation of a hypomotile stomach, were given either 10 mg cisapride or placebo in a double-blind manner (10 patients per group). The movement of a 250-ml barium meal was assessed by means of television fluoroscopy performed at regular time intervals. Cisapride significantly improved antral contractility and enhanced gastric emptying compared with placebo. Deep peristaltic waves occurred over the entire small bowel, and motility and small bowel transit time of the barium meal were significantly increased in the cisapride group compared with the placebo group. The study demonstrates that when a carefully defined protocol is observed, fluoroscopy following barium ingestion offers considerable potential in the assessment of gastrointestinal motility. PMID- 8516653 TI - Cisapride in chronic dyspepsia: results of a double-blind, placebo-controlled trial. AB - The efficacy and tolerability of cisapride in chronic dyspepsia was evaluated in a randomized, double-blind, placebo-controlled study. After 4 weeks' treatment with oral cisapride 10 mg three times daily (n = 14), bloating and epigastric discomfort were significantly reduced compared with placebo (n = 15; p < 0.05). Moreover, the global response to treatment was excellent or good in 71.4% of patients in the cisapride group versus 20.0% with placebo. No significant side effects were observed. It is concluded that cisapride is an effective and well tolerated treatment for chronic dyspepsia. PMID- 8516654 TI - Factors affecting short- and long-term outcome of a short therapeutic trial with cisapride in dyspeptic patients. AB - In a Dutch general practice trial conducted in 599 patients with symptoms of dyspepsia, the response to 5 mg cisapride three times daily was rated excellent or good in 61% of patients at week 2. On increasing the dose to 10 mg three times daily in 132 patients with poor to moderate response, the result at the end of treatment was rated as good or excellent in 45% of these patients, and the mean symptom score further decreased significantly (p < 0.05). The longer the pretreatment duration of dyspeptic symptoms, the lower was the overall response rate to cisapride short-term therapy (80% in patients with complaints < 3 months versus 50% in those with complaints > 4 years). Cisapride also proved effective in patients previously treated with prokinetic agents (72% response rate), antacids (66%) and H2-receptor antagonists (48%). On long-term follow-up, dyspepsia relapse rates among the total patient population (n = 357) and the patient sample fully 'cured' after 4 weeks of cisapride (n = 226) were respectively 30% and 27% after 6 months. Factors affecting recurrence of dyspeptic symptoms included age, duration of symptoms prior to trial entry and mean symptom score at end of the treatment study, but not the symptom severity prior to treatment. Relapsing patients presented mainly with the same symptom profile as at the first study, and the majority (88%) responded well to repeated treatment with cisapride. In conclusion, most patients responded well to a short therapeutic trial with cisapride and remained free from relapse in the subsequent 6 months. Repeated treatment in patients with recurrent symptoms appeared to be successful. PMID- 8516655 TI - Functional dyspepsia versus other functional gastrointestinal disorders: a practical approach in Belgian general practices. AB - This paper identifies the symptom profile associated with the four main diagnoses of functional digestive disorders (dyspepsia, gastro-oesophageal reflux disease (GORD), gastritis, and constipation) made by general practitioners in Belgium. Results are also presented from a multicentre study in which the effects of cisapride, administered as an oral tablet or suspension, were evaluated in patients with these functional digestive disorders. Analysis of symptom patterns revealed that early satiety and postprandial abdominal bloating were the most prominent symptoms, followed by eructation (belching), heartburn, regurgitation, postprandial epigastric burning or discomfort, and nausea. These symptoms occurred in all diagnostic groups. However, different symptom patterns were associated with each of the disorders; for example, heartburn and regurgitation were the core symptoms in patients diagnosed as having GORD, early satiety and abdominal bloating were characteristic of patients diagnosed with dyspepsia, and fasting or postprandial pain were characteristic of patients given the diagnosis of gastritis. Therefore, it appears that these diagnoses used by general practitioners in Belgium closely correspond to reflux-like, dysmotility-like and ulcer-like dyspepsia, as defined by an international working party. Cisapride improved the core symptoms in about 80% of patients with GORD or dyspepsia, relieved all epigastric symptoms in about 80% of patients with gastritis, and significantly decreased the use of laxatives and increased stool frequency in constipated patients. Cisapride was well tolerated and thus appears to be a useful option in the treatment of functional digestive disorders in a general practice setting. PMID- 8516656 TI - Dyspepsia and dyspepsia subgroups in Japan: symptom profiles and experience with cisapride. AB - In 240 patients with symptoms of dyspepsia, recruited consecutively and investigated in 12 hospitals in Japan, 24.2% were diagnosed having organic dyspepsia; 75.8% had functional dyspepsia, of whom 63.2% were diagnosed by the investigator having dysmotility-like, 13.7% ulcer-like, 11.5% reflux-like, and 11.5% non-specific dyspepsia. There was, however, considerable overlap of symptom profiles. Cisapride therapy initiated in functional dyspeptic patients resulted in moderate or marked improvement in 79.1% of the patients with the highest response rates for dysmotility-like (85.2%), reflux-like (81.0%), and non specific dyspepsia (76.1%) (versus 52.0% for ulcer-like dyspepsia). PMID- 8516657 TI - Risk factors, co-medication, and concomitant diseases: their influence on the outcome of therapy with cisapride. AB - In a 28-day non-blinded study of 1071 patients with functional dyspeptic symptoms in a general practice setting, 666 presented with mainly typical symptoms of functional dyspepsia and received 5 mg cisapride three times daily, while 405 with predominating symptoms indicative of gastroesophageal reflux received 10 mg cisapride three times daily. On the basis of an anamnestic risk factor analysis for organic lesions, 'low-risk' patients were to be treated directly with cisapride, while for 'high-risk' patients a more thorough gastrointestinal examination was recommended before starting cisapride. Of patients in the dyspepsia group 75% reported a good or excellent response; the corresponding rate was 80% in the reflux group. Low-risk patients in both groups tended to respond better than high-risk patients (mean difference, 11%). Patients and investigators reached identical assessments of response. Concomitant antacids, calcium antagonists, beta-blockers and sedatives did not affect the results, but concomitant NSAIDs reduced the mean improvement rate by 14% (p < 0.01). Adverse effects such as abdominal cramps and loose stools were uncommon (< or = 3.4%). PMID- 8516658 TI - Efficacy of cisapride in functional dyspepsia resistant to domperidone or metoclopramide: a double-blind, placebo-controlled study. AB - A double-blind, placebo-controlled trial was performed to determine the therapeutic efficacy of cisapride in patients with refractory functional dyspepsia. A total of 147 patients with functional dyspepsia characterized by prominent epigastric pain or discomfort were randomized to 2 weeks' treatment with metoclopramide or domperidone (both 30 mg/day); of these, 53 patients unresponsive to dopamine antagonist treatment were randomized to cisapride 30 mg/day or placebo for an additional 2 weeks. Metoclopramide and domperidone produced comparable alleviation of epigastric symptoms; global efficacy was good or excellent in 62% and 57% of patients, respectively. In refractory patients, cisapride tended to display greater efficacy than placebo against epigastric pain, particularly at night. Global assessments of efficacy significantly favored cisapride over placebo, with good or excellent ratings in 65% and 32% of patients, respectively. Cisapride was well tolerated. Thus, cisapride appears to be an effective agent in functional dyspepsia unresponsive to other gastrokinetic agents. PMID- 8516659 TI - Cisapride in functional dyspepsia: a double-blind, placebo-controlled randomized trial in general practice patients. AB - This trial included patients from general practice with endoscopy-negative chronic dyspepsia and epigastric pain or discomfort. Eleven eligible patients with sufficiently severe dyspeptic symptoms after a 2-week placebo run-in period were entered into a 4-week, parallel group, double-blind randomized comparison of 10 mg cisapride three times daily and matched placebo, and were subsequently evaluable. Symptoms were comparable in the two treatment groups at the start of double-blind treatment. The cisapride group had a significantly greater reduction in the frequency of daytime epigastric pain/discomfort and the frequency and severity of nocturnal pain/discomfort after 2 weeks. After 2 weeks, all six cisapride recipients were free of nocturnal pain, compared with only one of five placebo recipients. After 4 weeks of double-blind therapy, improvements in the placebo group had reduced between-treatment differences, with five of six cisapride recipients and three of five placebo recipients being free of nocturnal pain. Cisapride was well tolerated. PMID- 8516660 TI - A German drug-monitoring study in general practice patients receiving cisapride for functional dyspepsia. AB - An open prospective drug monitoring study was undertaken to assess the efficacy and tolerability of 5 mg cisapride three times daily in 37,925 general practice patients with functional dyspepsia. Short-term (mean, 4 weeks) cisapride treatment was associated with a significant reduction in overall dyspeptic symptom scores and improvements in scores of all eight individual dyspeptic symptoms (epigastric discomfort, fullness, nausea, bloating, heartburn, acid regurgitation, loss of appetite, and vomiting). Physician's and patient's subjective global evaluations of antidyspeptic efficacy were good or very good in 80% to 90% of cases. The tolerability of cisapride was judged to be satisfactory, good or very good in approximately 95% of patients, with adverse drug reactions being documented in 4.8% of patients. Of these, diarrhea/loose stools (2.5% of all patients) and headache (0.7%) were most frequent. Premature treatment withdrawal due to poor tolerability was necessary in only 0.35% of patients. PMID- 8516661 TI - Effect of cisapride therapy for severe dyspepsia on gastrointestinal symptoms and quality of life. AB - Quality of life measures have received little attention in evaluation of therapy for dyspepsia. To examine the effect of cisapride on gastrointestinal symptoms and quality of life measures, we studied eight patients with chronic, severe dyspepsia, before and after therapy with cisapride (20 mg three times daily) for 12 months. Gastrointestinal (GI) Total Symptom Score (TSS), Overall Patient Assessment (OPA), and quality of life by both trait (Minnesota Multiphasic Personality Inventory (MMPI)) and physical function (Sickness Impact Profile (SIP)) were measured at base line and at month 12 of cisapride therapy. Results showed significant improvement in TSS, OPA, and the MMPI Depression and Anxiety scales (all, p < 0.05). Improvement in the SIP physical dimension score approached significance (p = 0.065). We conclude that, in this group of patients with severe dyspepsia, both GI symptoms and quality of life measures improved with 12 months of cisapride therapy. These quality of life measures may prove useful in evaluating the efficacy of drug treatment for dyspepsia. PMID- 8516662 TI - Discovery and development of antipicornaviral agents. AB - The rhinovirus and enterovirus members of the picornavirus family are responsible for the majority of the mild upper respiratory infections most often referred to as the common cold as well as more serious illnesses including myocarditis. Much progress has been made in the identification and development of antiviral agents which specifically target the capsid of the picornaviruses. Preclinical and clinical efficacy data will be discussed on the WIN series of antiviral agents which were the result of a conventional drug discovery approach. The design of new agents is being assisted by the availability of atomic resolution data on the interaction of this class of antiviral agents with the viral capsid. PMID- 8516663 TI - Immunomodulating factors and immunosuppressive drugs in the therapy of myocarditis. AB - This review examines the immunologic rationale for immunosuppressive and immunomodulating therapy in man and experimental animal. The controversy if immunosuppressive treatment is beneficial in myocarditis will continue even after the American myocarditis trial. It is obvious that in viral heart disease immunosuppressive drugs should be avoided, in autoreactive forms of myocarditis with proven humoral and cellular effector mechanisms they may be used in controlled randomized trials to validate or negate their benefit. Immunomodulating factors e.g. immunostimulatory or antiviral substances like ribaverin, the interleukins and interferons have demonstrate some effect in experimental animal myocarditis but proof for the efficiency in man is still lacking. Hyperimmunoglobulin therapy appears to be of particular interest because of the little side effects and positive results in CMV associated myopericarditis in man. PMID- 8516664 TI - Etiological diagnosis of viral heart disease. AB - Myocarditis is a relatively common complication of viral infections and for example enteroviruses, influenza-viruses and adenoviruses are found in association with this disease. However, in many clinical myocarditis cases the etiology remains unknown when the present routine methods are used for viral diagnosis. The availability of myocardial biopsy samples has now made it possible to analyse the presence of viruses and viral components directly in the heart muscle. In particular the molecular methods, in situ hybridization and polymerase chain reaction (PCR), have recently given promising results. Furthermore, the use of these methods is casting new light in the viral etiology of idiopathic dilated cardiomyopathy. PMID- 8516665 TI - Clinical diagnosis of myocarditis and dilated cardiomyopathy. AB - The diagnosis of acute infectious myocarditis can be made on clinical grounds with reasonable certainty. Dynamically evolving electrocardiographic, echocardiographic, and serum cardiac enzyme level changes in a patient with symptoms of both an infection and a heart disease are the basis for the diagnosis. In contrast, the diagnosis of lymphocytic or giant cell myocarditis can be made only on the basis of an endomyocardial biopsy finding. The diagnosis and differential diagnosis of dilated cardiomyopathy are discussed in brief. PMID- 8516666 TI - Morphological recognition of viral heart disease. AB - A large number of endomyocardial biopsies have been analysed from 1.978 patients clinically diagnosed as suffering from dilated cardiomyopathy. In 1.125 patients non-specific changes of a dilated, hypertrophied myocardium were found consistent with a clinical diagnosis of dilated cardiomyopathy. The most interesting group consisted of 676 patients among which 549 cases showed clear evidence of myocarditis. The so-called "Dallas Criteria" have been described in detail and categorised into acute, active, on-going, resolving (healing) and resolved (healed) phases. Categorization is important for therapeutic reasons. Morphological analysis performs the bases upon which other investigations can be undertaken. PMID- 8516667 TI - The epidemiology of viral heart disease. AB - The enteroviruses, especially the Coxsackie B viruses, predominate as causative agents in myopericarditis and may be involved in the pathogenesis of dilated cardiomyopathy. Some studies suggest that these and other viruses might be implicated even in atherosclerosis and myocardial infarction. True incidence data of myopericarditis in the population at large are hardly feasible, since the disease is most often mild or subclinical. The long-term prognosis is favorable even in a majority of hospital-treated patients. A recent histopathological study of unselected autopsy cases employing the "Dallas criteria" for a diagnosis shows a myopericarditis incidence of 1.06 per cent. A link between myopericarditis and dilated cardiomyopathy is supported by findings of enteroviral RNA in biopsies and explanted hearts in the latter condition. A partly new panorama of viral heart disease is emerging in heart transplant recipients and AIDS patients. PMID- 8516668 TI - Cardiomyopathies in children. AB - The epidemiology, etiology and natural history of cardiomyopathies in children are still largely unknown but supposed to differ from those of adults. High mortality rates and lack of specific therapy are typical for this heterogeneous group of heart diseases. In recent years, the application of the techniques of molecular biology has provided new information about the possible etiologies of both hypertrophic and dilated cardiomyopathy. However, much experimental and clinical research is needed for better understanding of the pathogenesis of cardiomyopathies and for developing treatment and prevention. PMID- 8516669 TI - Monogamy and the prairie vole. PMID- 8516670 TI - Autism. PMID- 8516671 TI - Eugenics revisited. PMID- 8516673 TI - SNAPs and SNAREs. Protein hooks help vesicles grab cell membranes. PMID- 8516672 TI - Living cure. Insulin-secreting implants approach human testing. PMID- 8516674 TI - David's victory. Gene causing "bubble boy" illness is finally found. PMID- 8516675 TI - The centrosome. PMID- 8516676 TI - On computers, waiting, and the patient's vulnerability. PMID- 8516677 TI - Munchausen's syndrome: a brief review. AB - Munchausen's syndrome, a chronic factitious disorder, is appropriately named after an 18th century German nobleman who was noted for his story-telling ability. The disorder is an interesting oddity; however, it may not be as uncommon as most think. Behavioral motivations and clinical presentations of the illness are variable and make diagnosis difficult. Approaches to treatment vary widely and success remains elusive. As a result of their manipulative behavior and their desire not to "respond" to medical intervention, these patients are extremely frustrating to treat. The illness represents an emotional and economic stress on an already stressed medical system. If the diagnosis is suspected, efforts should be made to direct the patient toward expert sources for further evaluation and treatment. PMID- 8516678 TI - Recent changes in recommendations for antihypertensive therapy. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. PMID- 8516679 TI - How well do you manage your malpractice risks?--Part I. PMID- 8516680 TI - The specialty dilemma. PMID- 8516681 TI - Determinants of peak flow rate among Hutterite farmers. AB - Observations from respiratory studies of over 1000 Hutterites and 200 control subjects indicated that the percent predicted peak flow rate values were 20% lower among Hutterites than control subjects. The purpose of this study was to determine if the decreased peak flow rate values among male Hutterites were a function of decreased airway patency or decreased respiratory muscle strength. Peak flow rate, muscle and lung function and the prevalence of respiratory symptomatology and disease were evaluated in 27 males from two Hutterite colonies. In one group almost all members consistently used masks while performing farming tasks, while 41% of members from the other colony used masks intermittently. Results suggest that peak flow rate values are decreased predominantly due to decreased airway patency associated with a higher prevalence of respiratory symptoms and disease and are not limited by respiratory muscle strength. PMID- 8516682 TI - To kill a messenger. PMID- 8516683 TI - Biotechnology: a theoretical reality. PMID- 8516684 TI - Human health effects of nonionizing electromagnetic radiation. PMID- 8516685 TI - Spatial and temporal patterns of airborne metal pollution: the value of low technology sampling to an environmental epidemiology study. AB - To investigate an epidemic of respiratory cancer in Armadale, central Scotland, its air pollution was studied. During a period of 18 months, low technology samplers were exposed at 47 sites in the town to monitor the local variations in contamination by atmospheric metals. The samplers were two types of lichen and two types of moss, one of each type being a transplant and the other an in situ sampler. Following each exposure, the comparability of the samplers' uptake and retention of the metals was assessed. The sources of the metals and the effects of environmental variables on the pollution patterns were investigated through statistical analyses of spatial and temporal trends in the data. The spatial patterns of the metals indicated the steel foundry in the town as the major source of most of the pollutants. The temporal patterns, although less statistically significant, suggested the pollution might have been affected by some meteorological factors and by the foundry's output, but not by the output of the other main industry in the town, i.e. a brickworks. The types of sampler showed a general similarity of pollution pattern, but with some differences which indicated that some types of sampler were more suitable than others for particular forms of survey. Low technology sampling can provide information about short-distance and short-term changes in the patterns of airborne pollution by metals, thereby assisting the interpretation of epidemiological patterns of respiratory disease. PMID- 8516686 TI - Tuberculosis: from history to current management. PMID- 8516687 TI - Tuberculosis in the normal host: radiological findings. PMID- 8516688 TI - Pulmonary tuberculosis in immunocompromised hosts: epidemiological, clinical, and radiological assessment. PMID- 8516689 TI - Infection caused by nontuberculous mycobacteria: clinical aspects. PMID- 8516690 TI - Pulmonary infections with atypical mycobacteria in the normal host. PMID- 8516691 TI - Disseminated nontuberculous mycobacterial infections in immunosuppressed patients. AB - In summary, DNTM is an uncommon cause of infection in non-AIDS immunocompromised patients, but it is seen with increasing frequency as a late complication in AIDS patients who are severely debilitated. Non-AIDS patients may have pulmonary symptoms and parenchymal abnormalities on chest radiographs. These patients apparently may have clinically significant pulmonary infection. In contrast, AIDS patients with DNTM are unlikely to have clinically significant pulmonary disease. Although the lung is a common site of infection in these patients, they usually do not have pulmonary symptoms related to NTMB infection. Chest radiographs in these patients may show hilar or mediastinal adenopathy and/or pleural effusion. It is uncertain whether the parenchymal infiltrates noted in these patients are caused by NTMB or by coexisting processes. It is suspected that pulmonary NTMB in the AIDS patient is not likely to produce pulmonary parenchymal abnormalities on the chest radiograph. PMID- 8516692 TI - Pulmonary tuberculosis in children. AB - TB is no longer the scourge it once was, but it remains an important cause of morbidity and mortality worldwide. Fueled by increasing poverty, homelessness, immigration, drug abuse, declining prevention programs, and the HIV epidemic, its incidence in the United States has increased dramatically. The complex natural history of pulmonary TB in children is reflected in its varied radiographic manifestations. Strict distinction between "adult" and "childhood" patterns of TB should be avoided (Fig 16). In general, adenopathy is the footprint of childhood primary pulmonary TB, with or without a readily apparent primary parenchymal focus or pleural effusion. Infants and young children are more likely to present with adenopathy only than their older counterparts. The pediatric tracheobronchial tree is particularly susceptible to compression by surrounding nodes, producing segmental atelectasis, or less commonly, obstructive emphysema. Self-limited lymphohematogenous dissemination is the rule, but actual miliary disease is the exception. Pediatric postprimary TB, when it occurs, is usually observed in adolescents. It is characterized by parenchymal disease with an anatomic bias for the upper lung zones. Proper image interpretation is inextricably dependent on an understanding of the pathogenesis of this fascinating and often baffling illness whose appearance widely varies depending on host age and immunity as well as the virulence of the organism itself. PMID- 8516693 TI - Case of the season. Spondyloarthropathy of renal dialysis. PMID- 8516694 TI - Etiology of children's spinal injuries at Rancho Los Amigos. AB - A review of 277 patients under the age of 16 years admitted to the pediatric spinal injury unit at Rancho Los Amigos Medical Center from 1960 to 1989 showed that 70% of the patients were male; complete and incomplete injuries were about equal; and the average age was 8.8 years. The cause of spinal injury by time period revealed that earlier time periods had etiologies similar to those reported in previously published series. Although the incidence of these traditional causes remained constant, violent injuries by gunshot steadily increased with time. In the most recent 5-year period, gunshot wounds equaled motor vehicle injuries as the most frequent cause of a child's spinal injury admitted to this hospital. Gunshot wound victims averaged 12 years old, 80% were male, and most were thoracic level paraplegics. Half of the 50 adolescents (12-16 years old) injured during the last 5 years were gunshot victims. PMID- 8516695 TI - The surgical management of Scheuermann's disease. AB - Thirty patients of a group of 39 patients with Scheuermann's kyphosis who underwent posterior spine fusion using large-diameter Harrington compression instrumentation were reviewed with a mean follow-up of 71.8 months. The mean curve before surgery was 71.5, and at follow-up, 37.7. The mean loss of correction at review was 6. This procedure was effective in adults with a fixed deformity as long as no anterior bony bridging existed. The authors believe that posterior Harrington instrumentation and spine fusion offer excellent correction of deformity at long-term follow-up without the added morbidity of a second procedure. PMID- 8516696 TI - Biomechanics of indirect reduction of bone retropulsed into the spinal canal in vertebral fracture. AB - The biomechanics of indirect reduction of bone fragments retropulsed into the spinal canal in a burst fracture were investigated. In this model, tunnels were created in vertebrae L1 and C5 oriented anterior-to-posterior, allowing access to the posterior longitudinal ligament. A probe containing a load-sensing tip was passed through the tunnel. Both the location of the tip and the load acting on it by posterior deflection of the posterior longitudinal ligament were measured. In the lumbar spine, distraction was applied by spinal instrumentation that also permitted independent kyphotic-lordotic alignment of the vertebrae. In the cervical spine, axial traction was applied through direct loading. Several clinically relevant observations were made. It was not possible to produce an anteriorly directed force in the posterior longitudinal ligament at less than 35% canal occlusion, partly because the posterior longitudinal ligament stands away from the midbody of the vertebra. Distractive forces of up to 150 N were applied in the lumbar spine, which were nearly equal to the tensile breaking strength of the isolated posterior longitudinal ligament. Regardless of the relative sagittal plane angulation of the vertebrae, distraction was the governing factor in generating force in the posterior longitudinal ligament. Because positioning the vertebrae in lordosis before applying distraction significantly slackens the posterior longitudinal ligament, it is suggested that distraction be applied before angular positioning of the vertebrae is performed. PMID- 8516697 TI - Degenerative symptomatic lumbar scoliosis. AB - Scoliosis with progressive deformity can develop late in life. The authors studied 200 patients older than age 50 years with back pain and recent onset of scoliosis. Seventy-one percent of patients were women, and no patient had undergone spinal surgery. The curves involved the area from T12 to L5 with the apex at L2 or L3 and did not exceed 60 degrees. Degenerative facet joint and disc disease always were present, and the curves were associated with a loss of lumbar lordosis. Forty-five patients with severe pain and neurologic deficits were studied using myelography. Indention of the column of contrast medium was seen at several levels but was most severe at the apex of the curve. It was least severe at the lumbosacral joint. The curves progressed an average of 3 degrees per year over a 5-year period in 73% of patients. Grade 3 apical rotation, a Cobb angle of 30 or more, lateral vertebral translation of 6 mm or more, and the prominence of L5 in relation to the intercrest line were important factors in predicting curve progression. PMID- 8516698 TI - Reflex activation of gluteal muscles in walking. An approach to restoration of muscle function for patients with low-back pain. AB - Gluteal activation and pelvic stability often are decreased in chronic low-back pain sufferers, but the importance of motor control and programming in treatment has not been fully evaluated. This study investigated whether gluteal muscles could be activated more effectively by stimulating the proprioceptive mechanism during walking. Labile support, through wearing "balance shoes," offered facilitation of cerebellovestibular circuits. Electromyographic recordings of gluteus maximus and medius in 15 healthy subjects were made during barefoot and balance shoes walking before and after 1 week of facilitation. Significant increases (P < 0.0002) in gluteal activity and significant decreases (P < 0.01) in time to 75% maximum contraction, demonstrated the value of sensorimotor elicitation of subconscious and automatic responses in muscles often weakened in back pain sufferers. PMID- 8516699 TI - An assessment of the reliability of the Scoliometer. AB - Accurate noninvasive measurements of spinal curvature are crucial in planning treatment and assessing curve progression in adolescent idiopathic scoliosis. An inter-rater agreement trial and an intrarater agreement trial were undertaken to estimate the reliability of axial rotation measurement using the Scoliometer (Orthopedic Systems, Inc., Haywood, California). In the inter-rater trial, two orthopedic surgeons and two orthopedic surgery residents independently measured the thoracic and lumbar axial rotations of 22 patients with idiopathic scoliosis using the Scoliometer. In the intrarater, trial a single orthopedic surgeon measured the thoracic and lumbar axial rotations of 25 patients on four separate occasions with the Scoliometer. Inter-rater agreement using the Scoliometer to estimate the magnitude of the hump (in centimeters) in the thoracic and lumbar regions was poor (intraclass correlation coefficient, Rho = 0.57 and Rho = 0.76 for the thoracic and lumbar regions, respectively). Inter-rater agreement using the Scoliometer to estimate the degree of axial trunk rotation was better (Rho = 0.81 and Rho = 0.82 for the thoracic and lumbar regions, respectively). Intrarater agreement using this device to estimate the magnitude of the hump (in centimeters) in the thoracic and lumbar regions was good (Rho = 0.90 and Rho = 0.84 for the thoracic and lumbar regions, respectively). Intrarater agreement using the Scoliometer to estimate the degrees of curvature was outstanding (Rho = 0.995 and Rho = 0.998 for the thoracic and lumbar regions, respectively). These results indicate that the Scoliometer can be a reliable noninvasive method for repetitively assessing spinal axial rotation when used by a single trained observer. PMID- 8516700 TI - Long-term results of Harrington instrumentation in idiopathic scoliosis. AB - The long-term effect of Harrington instrumentation was investigated using posteroanterior radiographs and computed tomographic measurements preoperatively, postoperatively, and at a mean follow-up at 10.8 years in 33 patients with idiopathic scoliosis. No patient was lost from long-term follow-up. At follow-up, the mean Cobb angle was improved by 23.7 (40%) compared with the preoperative findings. The rotation of the apical vertebra was increased significantly. The rib hump, the translation of the apical vertebra, and the sagittal diameter of the thoracic cage were unchanged. At follow-up, the mean thoracic kyphosis was 17.3, and lumbar lordosis was 22.0. This study demonstrated that the long-term effect of Harrington instrumentation was limited to an improved Cobb angle; no correction of the rotational or sagittal deformities were achieved. PMID- 8516701 TI - The results of surgical treatment for adult scoliosis. AB - This study was done to define and characterize those adult patients with scoliosis who will have problems of pain and/or progression leading to a surgical procedure and to review the results of these surgical procedures. The authors reviewed the cases of 49 adult patients who had undergone surgical treatment for scoliosis (average follow-up, 34 months; range, 24-140 months). The patients were categorized according to age, which allowed analysis of the data comparing age and the incidence and level of pain, age versus the degree of curvature, and age versus the incidence of progression. The relative incidence of pain and progression as indications for surgery were found to vary with respect to age. In the younger groups, progression was more often the indication for surgery than in the older groups. The younger groups also had larger curves than did the older groups, on average. The degree of pain was not found to correlate with the magnitude of the deformity. Surgical complications occurred in 20 patients; however, 14 of these were minor complications during the perioperative period, which did not result in any sequelae. Surgical treatment can be done with a relatively low serious complication rate and good results in terms of pain relief and reasonable correction of the deformity. PMID- 8516702 TI - The neurologic sequelae of cervical spine facet injuries. The role of canal diameter. AB - Neurologic outcomes were correlated with the cervical canal diameter for 33 patients who sustained unilateral or bilateral facet fractures, dislocations, subluxations, or perch injuries during a 9-year period. Lateral roentgenograms (target distance, 72 in.) were used to measure the canal and calculate the canal body ratio (Torg's ratio) at the level of the vertebral injury. Frankel's classification system was employed to compare initial and final neurologic function. The most important factors that determined the long-term functional results after unilateral or bilateral injuries in the cervical spine were the degree of vertebral trauma and the severity of the initial neurologic deficit. There was no correlation between the preinjury canal diameter or ratio and the severity of neurologic injury or the prognosis. Also, neurologic injuries were more common and more severe in patients with bilateral facet injuries. No patients with complete injuries had an improvement in their Frankel grade. PMID- 8516703 TI - Clinical classification as a predictor of therapeutic outcome after cervical epidural steroid injection. AB - A retrospective analysis was done on 100 patients who had received cervical epidural steroid injections for neck pain and cervical radiculopathy to identify the predictors of outcome after such treatment. Potential predictors of outcome were assessed individually and then simultaneously with a multiple-regression model. Patients with radicular symptoms and signs had the best pain relief in contradistinction to those with axial (neck) pain. A clinical classification model predicting the outcome and an algorithm for the use of such injections in the treatment of cervical radiculopathy were developed. PMID- 8516704 TI - Evaluation of intraoperative somatosensory-evoked potential monitoring during 100 cervical operations. AB - Continuous intraoperative somatosensory-evoked potential monitoring during scoliosis surgery, along with improved instrumentation techniques, has contributed to the reduction of neurologic injury from 4-6.9% to 0-0.7%. To assess whether somatosensory-evoked potential monitoring might play a similar role in cervical surgery, the authors compared the morbidity and mortality rates associated with 218 patients who were not monitored and were operated on between 1985-1989 with those found in 100 consecutive somatosensory-evoked potential monitored procedures done from 1989-1991. The cervical procedures were conducted for disc disease, stenosis, spondylosis, and ossification of the posterior longitudinal ligament. Eight of 218 unmonitored patients became quadriplegic (3.7%) and 1 died (0.5%); no instances of quadriplegia and no deaths were encountered among the 100 monitored patients. The reduction of neurologic deficit was attributed in part to early somatosensory-evoked potential detection of vascular or mechanical compromise of the spinal cord or nerve roots and to the immediate alteration of anesthetic or surgical technique in response to somatosensory-evoked potential changes, i.e., reversal of systemic or "relative" hypotension, adjustment of operative position, release of distraction, and cessation of manipulation. Continuous intraoperative somatosensory-evoked potential monitoring also was a practical tool in monitoring cervical surgery. PMID- 8516705 TI - Innervation pattern of dorsal roots and their effects on the specificity of dermatomal somatosensory evoked potentials. AB - Dermatomal somatosensory evoked potentials are used to monitor individual nerve root function during degenerative spinal surgery. However, a less than 100% agreement between level(s) of dermatomal somatosensory evoked potentials abnormality and nerve root involvement has been reported. The purpose of this article was to determine the possible cause of this discrepancy. Results from humans suggest that variations in peripheral innervation patterns of the dorsal nerve roots are the main reason for dermatomal somatosensory evoked potentials discrepancy both for cervical and lumbar nerve roots. Because these variations cannot be controlled, the authors recommend that dermatomal somatosensory evoked potentials and additional neurophysiologic methods be used during degenerative surgeries to provide the surgeon with information about individual nerve root function. A patient profile for these methods was provided. PMID- 8516706 TI - Complementary angles. A simplification of sagittal plane rotational assessment in cervical instability. AB - The use of complementary angle measurement improves the physician's ability to quantify the magnitude of the angle of rotation directly. By constructing a right triangle, with its base determined by the inferior end plate of the vertebral body, the angle of sagittal plane rotation can be determined readily. A perpendicular line drawn from the inferior end plate of the vertebra to the adjacent superior vertebra's inferior end plate will create an acute angle. This angle is complementary to the angle of sagittal plane rotation for this motion segment. The sum of two complementary angles, the acute angle described and the angle of sagittal plane rotation is equal to 90. Assessment of cervical spinal stability is crucial to the physician caring for traumatized patients. A checklist previously was developed by others to evaluate spinal stability; this relied heavily on the findings of routine lateral radiographs. Differences in the angle of sagittal plane rotational of greater than 11 between adjacent vertebra were equivalent to two points on this checklist, and five points or more suggested instability. PMID- 8516707 TI - Short-term and long-term failures of anterior polymethylmethacrylate construct with esophageal perforation. AB - Three patients with a history of anterior spinal surgery treated with a polymethylmethacrylate construct had extrusion of their constructs. In two instances, there were life-threatening esophageal fistulas, mediastinitis, and sepsis 3 months to 10 years after the original surgery. Surgical treatment required removal of the construct, treatment of the esophageal injury, and use of new spinal stabilization. Based on their experience and a review of the literature, the authors strongly recommend against the use of polymethylmethacrylate alone in anterior procedures involving the cervical spine except to treat malignancies in patients with a short life expectancy. PMID- 8516708 TI - Cervical congenital kyphosis with atlantoaxial dislocation. A case report. AB - Congenital kyphosis and atlantoaxial dislocation in a 13-year-old boy was treated by a C1 laminectomy and C2-C5 laminoplasty with fusion from the occiput to C2. This resulted in postoperative neurologic deterioration, but a secondary anterior C3 vertebrectomy followed by a C2-C5 fusion helped restore neural function. In the presence of congenital cervical kyphosis, anterior rather than posterior decompression and fusion is recommended, particularly in the presence of a stenotic spinal canal. PMID- 8516709 TI - Infection of a Charcot spine. A case report. AB - Charcot spine is an unusual neuropathic arthropathy that may be found in patients with complete neurologic lesions of the spinal cord. The case presented represents a progressive destructive lesion of a Charcot spine, which, on extensive investigation and subsequent surgical arthrodesis, demonstrated an infectious process. Infection must be considered as a possible etiology in a destructive lesion of a Charcot spine. PMID- 8516711 TI - Magnetic resonance imaging and computed tomography in the evaluation of penetrating gunshot injury of the spine. Case report. PMID- 8516710 TI - Traumatic sacrolisthesis S1-S2. Report of a case. AB - A young patient 13 years of age with traumatic sacrolisthesis at S1-S2 accompanied by neurologic damage was initially treated by traction to reduce the S1 dislocation over S2, and later by posterior arthrodesis using the technique of Luque. The procedure resulted in good stability and the patient showed marked orthopedic and neurologic improvement. PMID- 8516712 TI - Lumbar lymphoma presenting as psoas abscess/epidural mass with acute cauda equina syndrome. A case report. PMID- 8516713 TI - Juxta-facet cysts. Report of two cases and review of clinicopathologic features. PMID- 8516714 TI - Herniated thoracic disc at T1-T2 with paraparesis. Transthoracic excision and fusion, case report with 4-year follow-up. PMID- 8516715 TI - Spina bifida occulta. Incidence in parents of offspring with spina bifida cystica. PMID- 8516716 TI - Traumatic anterior atlanto-occipital dislocation. A case report with survival. PMID- 8516717 TI - Pseudovisceral pain referred from costovertebral arthropathies. Twenty-eight cases. PMID- 8516718 TI - [The diagnosis of malignant lymphoma of the thorax: the value of CT in comparison with thoracic radiography--an evaluation study]. PMID- 8516719 TI - [Computed tomography of diffuse liver diseases. 1: Study methods-- steatosis hepatis--liver cirrhosis]. PMID- 8516720 TI - [Efficiency of CT-guided percutaneous drainage of an abdominal abscess]. PMID- 8516721 TI - [Diagnostic imaging of primary tumors of the gallbladder and bile ducts: sonography, CT, MRT and angiography]. PMID- 8516722 TI - [The treatment of an occlusion of the superficial femoral artery in relation to the angiographic findings]. PMID- 8516723 TI - [A pseudoaneurysm of the abdominal aorta--diagnosis using color duplex sonography]. PMID- 8516724 TI - [Cytogenetic studies in hematological diseases. Analysis of 185 cases]. AB - PURPOSE: To analyse the chromosomal abnormalities found at diagnosis in patients with malignant blood diseases. PATIENTS AND METHODS: Between june 1988 and january 1992, cytogenetic studies were performed at the Cytogenetics Laboratory of the Abel Salazar Institute for Biomedical Sciences on 185 patients with malignant blood diseases. Bone-marrow and/or peripheral blood cells were used for such studies, two simultaneous cultures being prepared at 24 and 48 hr, plus another one, stimulated with phytohemagglutinin, at 72 hr. Trypsin G-banding techniques were used for chromosome identification. Chromosomes were classified in accordance with the international system, and a clone was judged abnormal whenever two or more metaphases showed identical structural abnormalities or extra chromosome(s) and three or more metaphases lacked the same chromosome(s). RESULTS: Evaluable mitoses were found in 152 of the 185 cytogenetic studies performed (82.2%), pertaining to chronic myelogenous leukaemia (39/42), acute nonlymphoblastic leukaemia (40/43), myelodysplastic syndromes (10/17), acute lymphoblastic leukaemia (30/36), and chronic lymphoproliferative disorders (10/14). Chromosomal alterations, previously described in each diagnostic variety, were found in 69% of the cases with abnormal karyotype. The remaining patients (31%) had chromosomal abnormalities not reported consistently. CONCLUSIONS: The karyotype should be studied regularly in haematologic disorders since, although lacking precise prognostic implications, it may help gain information with regard to the genetic alterations in different blood diseases. PMID- 8516725 TI - [Adaptation of human bone marrow adipose tissue to different grades of hemopoietic cellularity]. AB - PURPOSE: To assess whether the variations in the number and size of the adipocytes are proportional, or not, to the changes of the fat tissue fraction (FF) associated to different degrees of hematopoietic cellularity of the bone marrow. MATERIAL AND METHODS: The material was made up of 28 specimens of bone marrow biopsy, from which 265 microscopic fields representing a wide range of FF were obtained. As index of proportionality, the ratio N/S (adipocyte number/size) was employed. RESULTS: The parameters FF and N/S showed a highly significant correlation (r = 0.89; p = 0.00000003) at low-normal FF range (< 40%), whereas at high FF range (> 40%), such a correlation was lacking (r = 0.01; p = 0.86). CONCLUSION: At low-normal FF the adipocyte number and size vary proportionally. Conversely, at high FF, in some cases a more marked increase of number and in other instances of adipocyte size is detected. Further investigations are needed to find out the responsible factors for this different behaviour. PMID- 8516726 TI - [Physiopathology of the antiphospholipid syndrome]. PMID- 8516727 TI - [Recombinant factor VIII]. PMID- 8516728 TI - [Determination of the protein requirement for the maintenance of the circulating red-cell mass in the adult rat]. AB - The present study was designed to provide direct information on the protein requirement of 12-month-old-female rats for maintenance of the circulating red cell mass (RCM). Different groups (7) of rats were fed during 30 days one of seven isocaloric diets containing graded levels of casein, from 0% to 10%. RCM was determined by the radio-iron-labelled red cell dilution method at the end of experimental period. Casein requirement level for maintenance of RCM, predicted as the point on the regression line where the value of the dependent variable (delta RCM/100 g body wt) was 0, was 3.6%. This value was identical to that predicted for the maintenance of body weight, which suggests that both are interrelated and that RCM is a function of the body weight. The relation also suggests that the anaemia developing in the adult rat in response to protein depletion could be a type of physiologic adaptation between the body oxygen transport system and the body mass. PMID- 8516729 TI - [Antiphospholipid antibodies and cerebral ischemic infarction in a 6-year-old boy]. AB - Lupus anticoagulant activity and anti-phospholipid antibodies (aPL) were found in a six-year-old child with cerebral ischemic infarction in the absence of any underlying disease. The association of these antibodies with thrombosis has been well documented in adult patients. In view of our observation, we believe that aPL may also be involved in the pathogenesis of arterial thrombotic events in childhood, and aPL should be systematically searched in these cases. PMID- 8516730 TI - [Selective chromosome painting using in situ hybridization]. AB - A method of in situ hybridization with entire chromosome-specific DNA libraries for visualizing individual human chromosomes has been developed and applied to the detection of structural aberrations in both metaphase and interphase cells. Unlabeled human genomic DNA is used to inhibit the cross-hybridization of repetitive sequences in the library that bind to multiple chromosomes. The remaining single-stranded DNA is hybridized to specimens of interest and detected with fluorescent or enzyme labeled biotin conjugates following post-hybridization washes. This general approach is called "chromosome painting" or "chromosomal in situ suppression (CISS)" hybridization. In the present report, DNA inserts from recombinant libraries from chromosomes 1, 4, and 9 has been applied on controls and patients in order to decorate specifically their complementary chromosomes. Numerical changes, deletions and chromosomal translocations involving these chromosomes can be strikingly visualized. PMID- 8516731 TI - [Multiple myeloma with cutaneous involvement in a patient with long-standing MGUS]. PMID- 8516732 TI - [Bilateral palpebral swelling as the initial manifestation of a disseminated non Hodgkin's lymphoma]. PMID- 8516733 TI - [Autotransfusion and the community hospital]. PMID- 8516735 TI - [Evaluation of the System 9000-AX autoanalyzer]. AB - PURPOSE: The aim of this study was to evaluate the haematologic autoanalyser System-9000 AX (Serono-Baker Diagnostics), which provides 15 parameters of red, white and platelet series and three histograms showing the cellular distribution curves according to the volume of each series. MATERIAL AND METHODS: The accuracy, precision, linearity, carry-over, effective speed and the effect of sample storage on results were studied. Moreover, the leucocyte differential count (LDC), false positive and negative results of the automated differential count and sensitivity, specificity and efficiency of LDC were analysed and compared with conventional methods: a Coulter VCS analyser and a Coulter S-Plus STKR. RESULTS: The accuracy of the results of three haematologic series was very good. In the LDC, the results for the middle and big cells were better in comparison with the manual method (r > 0.80) than the Coulter VCS, (r = 0.28 and 0.48 respectively). The percentage of LDC revisions and the false negative was higher in hospitalized patients than in outpatients (28.14 and 8.46% versus 12.56 and 2.18%). The most common anomalies were the left deviation, monocytosis and eosinophilia. The results of sensitivity, specificity and efficiency were greater than 80% in all cases, except for the sensitivity and efficiency of hospitalized patients, because of the greater number of false negatives. Precision and linearity were excellent in all the parameters studied. No significant contamination was observed among the samples (low carry-over percentage). The samples were stable for 24 hours at 4 degrees C. CONCLUSION: The System 9000 AX is a reliable analyser, which is fast and easy to operate. These characteristics allow this analyser to be a very useful tool for laboratories that require a rapid testing of samples. PMID- 8516734 TI - [Long-term survival in chronic myeloid leukemia: frequency and fundamental characteristics in a series of 100 patients]. AB - PURPOSE: To analyse the frequency and the main clinico-haematologic characteristics of the patients with Ph'-positive chronic myelogenous leukaemia (CML) with long survival. MATERIAL AND METHODS: Of a series of 100 patients with CML diagnosed in the chronic phase and treated in the conventional way at the "Farreras Valenti" School of Haematology between 1969 and 1982, and followed-up for at least 10 years, those surviving more that 8-10 years since the diagnosis were considered eligible for this study. Their clinico-haematological characteristics at diagnosis were compared to those of the remaining patients by means of the Student's t and Mann-Whitney's U tests, plus chi square with the Yates correction. The actuarial survival in the series was assessed according to the Kaplan and Meier method. The Sokal prognostic index was calculated in the longest survivors. RESULTS: The median survival of the series was 45 months (range: 4-171). Ninety-one patients died, 2 are alive in chronic phase and in 7 others the follow-up has been lost in the chronic phase. Eight patients survived more than 10 years and 14 more than eight years. Of these, six were men and eight women, 10 were under 50 years of age, one-half lacked splenomegaly at diagnosis and only 2 had Ph' chromosome mosaicism. According to the Sokal prognostic index, six of these patients were in the low-risk group, four were of intermediate risk, and four others were in the high-risk group. None of them had aplasia due to busulphan during the follow-up. When comparing the initial features of the patients surviving 8-10 years with those of the remainders, only the presence of a lower percentage of blast-cells (p = 0.03) and a lower number of blasts in peripheral blood (p = 0.01) in the former achieved statistically significant difference. CONCLUSIONS: These findings confirm the difficulty in identifying the CML patients with expected long survival at diagnosis. High numbers of cases must be analysed in order to attain definite conclusions in this regard. PMID- 8516736 TI - Paul C. Bucy, M.D. PMID- 8516737 TI - Festschrift. Paul C. Bucy, MD. PMID- 8516738 TI - The impact of Japan on the future of neurosurgery. PMID- 8516739 TI - Diversification in the concept of "birth and death": the controversy about "brain death and organ transplantation" in Japan. AB - There is a lot of hesitation in Japan in defining brain death as the death of the individual and in proceeding to organ transplantation. Regarding the diagnostic criteria of brain death, those issued by the Japanese Ministry of Health and Welfare in 1985 are sufficient for judgment of brain death. Many people, however, do not accept brain death as death of the individual, and even those who admit brain death as death of the individual hesitate to approve of the actual removal of organs from brain dead patients. Thus, the controversy about brain death in Japan appears to be separated from the objective of organ transplantation. PMID- 8516740 TI - Tethered cord in the adult mimicking the lumbar disc syndrome: report of two cases. AB - Two adult patients with tethered cords whose symptoms mimicked those of lumbosacral intervertebral disc herniation are reported. Neither one of the patients had cutaneous stigmata, and one had normal plain x-ray examination of the spine. Magnetic resonance imaging in both patients demonstrated tethering of the cord. Untethering of the cord resulted in disappearance of the symptoms in both patients. These unusual cases suggest that tethering of the cord must be included in the differential diagnosis of the herniated lumbar intervertebral disc syndrome. PMID- 8516741 TI - Brain tumors in pediatric patients at King Faisal Specialist Hospital and Research Centre. AB - We report our experience with brain tumors in pediatric patients, patients who came to our attention when they were aged 14 years or less. In general, the pattern of brain tumors at this Institution is similar to that reported in the neurosurgical literature. Fortunately we have modern diagnostic technology and modern operating instrumentation available to use for dealing with such lesions, which are often in their late stages. PMID- 8516742 TI - Cerebellar hemorrhage associated with capillary telangiectasia and venous angioma: a case report. AB - We report a case of recurrent cerebellar hemorrhage from a capillary telangiectasia associated with a venous angioma. Based on the findings in this case and a review of the literature, we concluded that the hemorrhage was from the telangiectasia and not from the associated venous angioma. The association between capillary telangiectasias and cavernous malformations and the established association of the latter with venous angiomas are reviewed. This case illustrates the complex interrelationship between these histologically distinct malformations and its influence on their potential to hemorrhage. PMID- 8516743 TI - Case report: successful removal of solitary metastatic cerebral malignant melanoma. AB - A 26-year-old female patient presented with a previous history of cutaneous malignant melanoma. She displayed signs of an expanding cerebral lesion due to a solitary metastasis of malignant melanoma; this was removed in toto, suggesting a cure. PMID- 8516744 TI - Spinal extradural cyst and kyphosis dorsalis juvenilis. 1937. PMID- 8516745 TI - Cerebral cysticercosis: a case report. AB - A case of cerebral cysticercosis is reported in a 49-year-old female who presented with headache, nausea, and vomiting. Lumbar CSF showed the findings of mild aseptic meningitis. CT scan revealed an enlargement of the left ambient cistern and a small cystic lesion in the left frontal cortex. MRI demonstrated multilobular cysts in the left ambient cistern with enhancement of their capsules, which compressed and distorted the midbrain. The cysts were surgically excised, and histological examination of the specimen disclosed characteristic features of cysticercus with viable larva. An excellent value of MRI in the diagnosis of intracisternal cysticercosis is emphasized. PMID- 8516746 TI - Spinal adhesive arachnoiditis. AB - Forty-one cases of spinal adhesive arachnoiditis are presented. The key points are, first, that lumbar disc lesions, their investigations and surgical treatment and the use of nonabsorbable contrast materials are the most common etiological factors and, secondly, that operation is the best treatment. It is our contention that the majority of patients so treated do experience some improvement in what otherwise can be an unbearable amount of pain and disability. The use of adsorbable, nonirritative contrast materials such as Iohexol Parenteral will result in a marked reduction in the frequency of occurrence of arachnoiditis. PMID- 8516747 TI - The preservation of hearing and facial nerve function in a consecutive series of unilateral vestibular nerve schwannoma surgical patients (acoustic neuroma). AB - Between January 1981 and February 1992, 102 non-NF-2 patients underwent removal of a unilateral vesitbular schwannoma. There were 54 women and 48 men. Eighty-six percent of patients with normal facial function preoperatively retained normal function (House score 1 or 2) postoperatively. Of the 64 patients with a functional cochlear nerve preoperatively, five had normal hearing (PTA < 25 dB, SB > 70%), five had near normal hearing (PTA < 45 dB, SD > 70%), four patients had preserved hearing (PTA < 50 dB, SD > 50%), and three patients had preserved cochlear nerve function (PTA > 50 dB, SD < 50%) after surgery. Hearing preservation was obtained in patients whose tumors were larger than 3 cm. Radiological follow-up revealed 10 patients with recurrent tumor, all but one asymptomatic. PMID- 8516749 TI - Stabilization of subaxial cervical spinal injuries. AB - With subaxial cervical spine fractures, it has not been established which injuries can be adequately stabilized by external orthoses and which will require surgical stabilization. After review of 64 consecutive patients with C3-C7 spinal injuries, fracture characteristics on admission roentgenograms were identified that accurately predict the success or failure of nonoperative management. These include evidence of severe ligamentous injury (SLI) and severe vertebral body injury (SVBI). The presence of SLI, SVBI, or both SLI and SVBI correlated strongly with nonoperative stabilization failure (p < 0.001, p = 0.002, and p = 0.004, respectively). Injuries without SLI or SVBI were all successfully stabilized by cervical orthoses. Additionally, characterizing injuries by evidence of SLI and SVBI directs the approach for surgical stabilization. PMID- 8516748 TI - Surgical removal of brainstem astrocytomas and hemangioblastomas: report of three cases and review. AB - The surgical removal of a brainstem astrocytoma or hemangioblastoma entails the risk of a major neurological injury, but if injury can be avoided, the benefits of surgery are considerable in some types of these tumors. Most brainstem astrocytomas are widely infiltrative diffuse tumors that frequency undergo malignant change and are not benefitted by surgery. However, dorsally exophytic brainstem astrocytomas, focal cervicomedullary astrocytomas, and focal brainstem astrocytomas have a more benign character and frequently are benefitted by surgical removal or other surgical intervention. Brainstem hemangioblastomas may be extramedullary tumors or cystic intramedullary tumors, and surgical removal of these tumors is usually possible and is the optimal treatment. Three cases are presented to illustrate that excellent results can be obtained by surgical resection of certain types of brainstem astrocytoma or hemangioblastoma. The clinical and radiographic characteristics and the results of surgical treatment for each of these types of brainstem tumor are discussed. PMID- 8516750 TI - The potential role of low field MR with open design in assessing ligamentous injury in acute cervical trauma. PMID- 8516751 TI - Tentorial and posterior cranial fossa meningiomas: operative results and long term follow-up: experience with twenty-six cases. AB - In spite of significant recent advancements in imaging technology, monitoring [12] and surgical techniques [1,5,7,18,21,24], complete and safe removal of tentorial and posterior fossa meningiomas remains a formidable challenge for most neurosurgeons [6,8,9,14,15,17]. This paper reviews our experience with 28 patients with tentorial and posterior fossa meningiomas. PMID- 8516752 TI - Central retinal vein occlusion in young adults. AB - Central retinal vein occlusion (CRVO) is usually seen in older adults and is often associated with systemic vascular disease. CRVO can be seen in young adults, and although it is occasionally associated with a systemic disease, in the majority of cases it occurs in an otherwise healthy patient with no known systemic disease or ocular problem. Inflammation of the central retinal vein has been proposed as a cause of the occlusion in young adults and for that reason it has been called papillophlebitis. The appearance of unilateral optic disc edema, dilatation, and tortuosity of the major retinal veins with a variable amount of retinal hemorrhage in young, healthy adults with complaints of blurred vision or photopsias has been called, in addition to papillophlebitis, benign retinal vasculitis, optic disc vasculitis, nonischemic CRVO, big blind spot syndrome, and presumed phlebitis of the optic disc. An approach to the diagnostic evaluation of the young adult with CRVO is presented. Although most eyes recover vision to better than 20/40, about one-fifth have significant visual loss, and many suffer ocular sequelae. Many treatment modalities have been tried for this entity, but no conclusive evidence exists that any treatment alters its natural history. PMID- 8516753 TI - Aicardi syndrome: more than meets the eye. AB - An eight-month-old girl with infantile spasms and apparent blindness had electroencephalographic findings compatible with Aicardi syndrome. In addition to optic nerve hypoplasia, there were multiple congenital retinal malformations in the right eye, including chorioretinal lacunae, anomalous retinal vessels, posterior scleral ectasia, and a peripheral fibrous ridge. Magnetic resonance imaging demonstrated agenesis of the corpus callosum, absence of the septum pellucidum, optic nerve and chiasmal hypoplasia, pachygyria, cortical heterotopias, colpocephaly, and hypoplasia of the cerebellar vermis. This patient illustrates the broad spectrum of cerebroretinal malformations now known to characterize Aicardi syndrome. PMID- 8516754 TI - Magnetic resonance angiography of vascular lesions causing neuro-ophthalmic deficits. AB - Magnetic resonance angiography (MRA) is a noninvasive, rapidly evolving technique for imaging the intra- and extracranial carotid and vertebrobasilar circulations. It may in some circumstances obviate conventional angiography and the accompanying risks associated with catheterization and contrast injection. MRA exploits the different physical properties between moving protons and stationary tissue to yield flow sensitive data in the form of anatomic images or velocity and flow measurements. Since patients with various vascular disorders may present exclusively with ophthalmologic signs and symptoms, it is expected that MRA will become more frequently utilized by ophthalmologists. The exact role of MRA in the workup of vascular disorders remains to be more precisely defined, pending the performance of additional well-controlled standardized studies. At present, MRA is utilized to complement the conventional spin-echo studies of patients with arterial and venous occlusion, vascular malformations, intracranial aneurysms, and neoplastic vascular invasion. With further refinements, it is expected that MRA will become a standard diagnostic tool for the evaluation of patients with vascular disorders. PMID- 8516755 TI - Familial malignant melanoma of the uvea and p53: a Victorian detective story. AB - In 1905, Parsons first described a family with a history of four generations with uveal melanoma associated with breast cancer. The family history has now been brought up to date using genealogical sources to determine the origin of this family which was traced to the East End of London in the early 19th century. In addition, immunohistochemical investigations have showed mutant p53, a tumor suppressor gene, in museum specimens of uveal melanoma after 150 years. This family probably represents the earliest example of the Li-Fraumeni syndrome on record. PMID- 8516756 TI - Coupling of computer modeling with in vitro methodologies to reduce animal usage in toxicity testing. AB - The use of in vitro data to support the development of physiologically based pharmacokinetic (PBPK) models and to reduce the requirement for in vivo testing is demonstrated by three examples. In the first example, polychlorotrifluoroethylene, in vitro studies comparing metabolism and tissue response in rodents and primates made it possible to obtain definitive data for a human risk assessment without resorting to additional in vivo studies with primates. In the second example, a PBPK model for organophosphate esters was developed in which the parameters defining metabolism, tissue partitioning, and enzyme inhibition were all characterized by in vitro studies, and the rest of the model parameters were established from the literature. The resulting model was able to provide a coherent description of enzyme inhibition following both acute and chronic exposures in mice, rats, and humans. In the final example, the carcinogenic risk assessment for methylene chloride was refined by the incorporation of in vitro data on human metabolism into a PBPK model. PMID- 8516757 TI - Overview--Air Force policy on halons. AB - Halons have been used for decades by the Air Force for a variety of fire protection applications. Their unique combination of effectiveness, low toxicity, ease of use, cleanliness, and low manufacturing cost appear to make them ideal for many situations. Unfortunately, they also deplete the earth's protective ozone layer and, consequently, their production is being phased out globally under the Montreal Protocol. United States legislation implementing the terms of the Protocol required an end to production of ozone depleting chemicals (ODCs) by the year 2000. In November 1991, the Air Force issued a policy requiring an end to ODC purchases by the end of 1997. In February 1992, President Bush announced an even more accelerated phaseout to 1995. The Montreal Protocol is expected to be amended to reflect the more aggressive US phaseout date. This accelerated date increases the urgency of the Air Force's search for ODC alternatives, especially for mission critical uses for which no alternatives have yet been identified. The search is complicated by the fact that the requirements an alternative must meet are unique to their specific application. This paper will provide an overview of the most important Air Force halon uses and review Air Force strategies for ensuring mission continuity until alternatives can be developed. PMID- 8516758 TI - Regulatory agency considerations and requirements for validation of toxicity test alternatives. AB - When developing an alternative toxicity test, one must first determine whether the alternative assay is to be used as a screen or as a replacement for the traditional toxicity test. An assay used as a screen will require less stringent acceptance criteria, for it is designed to answer fewer and less complex questions (e.g., the assessment of only potential teratogenicity). An assay used as a replacement will be used to establish hazard or lack thereof (safety). In other words, a replacement assay must clearly establish whether or not a chemical is a teratogen. One should also have knowledge of and experience with the in vivo assay to be replaced. This knowledge should be of not only the procedural aspects of the test but also the regulatory information it provides (i.e., how the results are used for hazard determination). Thorough consideration of the regulatory information is critical for a test intended to be used as a replacement. Validation should include intralaboratory and interlaboratory reproducibility of results from a standard protocol, an assessment of the qualitative and quantitative aspects of the test responses, and the use of a sufficient number of chemicals representative of the defined category of interest. PMID- 8516759 TI - Estimating the risks of liver and lung cancer in humans exposed to trichloroethylene using a physiological model. AB - Trichloroethylene (TCE) is a common and persistent environmental contaminant found in groundwater near most large cities and at Superfund landfill sites. In many cases, the groundwater is the primary source for water consumption. Because of the widespread distribution of TCE in the environment, a significant fraction of the population may ingest or inhale TCE over an extended period of time. Typically, environmental concentrations of TCE are in the ppb range. Health concerns for environmental exposure to TCE stem largely from positive outcomes in laboratory cancer bioassay studies with rodents at relatively high exposure concentrations. Epidemiological evidence that TCE is a human carcinogen is equivocal. PMID- 8516760 TI - Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effects on PBPK model predictions in a risk assessment for perchloroethylene (PCE). AB - When used in the risk assessment process, the output from physiologically based pharmacokinetic (PBPK) models has usually been considered as an exact estimate of dose, ignoring uncertainties in the parameter values used in the model and their impact on model predictions. We have collected experimental data on the variability of key parameters in a PBPK model for tetrachloroethylene (PCE) and have used Monte Carlo analysis to estimate the resulting variability in the model predictions. Blood/air and tissue/blood partition coefficients and the interanimal variability of these data were determined for tetrachloroethylene (PCE). The mean values and variability for these and other published model parameters were incorporated into a PBPK model for PCE and a Monte Carlo analysis (n = 600) was performed to determine the effect on model predicted dose surrogates for a PCE risk assessment. For a typical dose surrogate, area under the blood time curve for metabolite in the liver (AUCLM), the coefficient of variation was 25% and the mean value for AUCLM was within a factor of two of the maximum and minimum values generated in the 600 simulations. These calculations demonstrate that parameter uncertainty is not a significant potential source of variability in the use of PBPK models in risk assessment. However, we did not in this study consider uncertainties as to metabolic pathways, mechanism of carcinogenicity, or appropriateness of dose surrogates. PMID- 8516761 TI - A pharmacokinetic model for chromium. AB - Reduction of hexavalent chromium (Cr(VI) to trivalent chromium (Cr(III) and differential kinetics of Cr(III) and Cr(VI) are important determinants of the disposition and toxicity of chromium. A physiologically based model of chromium disposition in the rat has been developed. The model takes into account different absorption and reduction rates in the lung and gastrointestinal tract; different efficiencies of transfer of Cr(III) and Cr(VI) into tissues including erythrocytes, where Cr(VI) is reduced to Cr(III) and retained for an extended period of time; uptake and storage in bone; and reabsorption of chromium from the gastrointestinal tract. The model is shown to be capable of generating the observed distributions of chromium between plasma and erythrocytes in rats given Cr(VI) intragastrically, intraduodenally, or intratracheally. PMID- 8516762 TI - Limiting the uncertainty in risk assessment by the development of physiologically based pharmacokinetic and pharmacodynamic models. AB - Analysis of the default cancer risk assessment methodology suggests that the confidence interval usually associated with the prediction of an upper bound on risk underestimates the uncertainty in the risk estimate. This underestimate of uncertainty is based on the use of a large number of policy decisions or professional judgements that are incorporated into the methodology as exact values with no estimate of error. An alternative approach is to develop a comprehensive biologically based risk assessment that provides scientific data to substitute for many of the policy decisions of the default methodology. PMID- 8516763 TI - Dioxin hepatic carcinogenesis: biologically motivated modeling and risk assessment. AB - There are several key portions of the exposure-dose-response continuum with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) that have to be described quantitatively in developing a comprehensive mechanistically based dose-response model. These include: (i) the accumulation of TCDD in the target tissue, (ii) formation of a complex between dioxin and the Ah receptor, (iii) activation of transcription of growth regulatory genes by the TCDD-Ah receptor complex, (iv) cellular events on tumor initiation, promotion, and progression. Physiologically based pharmacokinetic (PBPK) models have been used as tools to integrate knowledge of the determinants of dioxin disposition, including specific binding to dioxin-inducible hepatic cytochromes, and to link TCDD tissue dosimetry with gene activation by pharmacodynamic (PD) models crafted to examine dioxin regulated gene expression. Biological studies on growth factor regulation suggest hypotheses for the role of these gene products in transient cell proliferation, prolonged growth suppression, and hepatic tumor promotion. We have used these hypotheses as the basis for stochastic cell growth models of the promotional events with TCDD and to suggest experimental strategies for future research. The combination of PBPK, PBPD and stochastic cell growth models provides a seamless exposure-dose-response model for TCDD induction of liver tumors in rodents. This comprehensive exposure-dose-response model should prove useful for risk assessment, experimental design, and analysis of noncancer endpoints with this potent, ubiquitous environmental contaminant. This paper outlines progress in formulating and evaluating these models for TCDD. PMID- 8516764 TI - The role of dichloroacetate in the hepatocarcinogenicity of trichloroethylene. AB - The induction of hepatic tumors in B6C3F1 mice treated with trichloroethylene (TRI) has been attributed to its metabolism to trichloroacetate (TCA). Trichloroacetate is an effective peroxisome proliferator in mice at blood concentrations that are readily achieved with carcinogenic doses of TRI. Recent data has demonstrated that both TCA and dichloroacetate (DCA) are capable of inducing liver tumors in B6C3F1 mice. Although long recognized as a metabolite of TRI, little attention has focussed on the role DCA might play in the hepatocarcinogenic effects of TRI. There are significant differences in the effects of DCA and TCA on the liver of B6C3F1 mice. Trichloroacetate treatment induces peroxisome proliferation, increases lipid deposition, and results in a marked accumulation of lipofuscin in the liver with long-term exposures. Dichloroacetate induces a markedly enlarged liver associated with a cytomegaly and large accumulations of glycogen. The cytomegaly is associated with the development of focal areas of recurrent liver necrosis which in turn lead to high levels of cell proliferation in the area surrounding these lesions. Induction of peroxisomes with DCA is transitory and the accumulation of lipofuscin is much less evident than with TCA treatment. Studies of TRI metabolism demonstrate that blood levels of DCA produced are sufficient to account for the hepatocarcinogenic effects of TRI. The rather low concentrations of DCA found in the urine of mice treated with TRI relative to TCA concentrations are due to the much more rapid and complete metabolism of DCA. These data do not support the conclusion that the hepatocarcinogenic effects of TRI are simply related to peroxisome proliferation. PMID- 8516765 TI - Human health and environmental toxicity issues for evaluation of halon replacements. AB - The Clean Air Act Amendments of 1990 require the US Environmental Protection Agency (EPA) to phase out production and use of ozone-depleting chemicals--among them, the fire suppressants, halons. As part of its rulemaking efforts EPA must evaluate the potential hazards to human health and the environment that could result from exposure to compounds that may substitute for halons. The EPA bases health hazard assessment on data obtained in studies involving short-term and long-term exposures. The former are used to evaluate potential risks of acute or delayed effects potentially resulting from short exposures at high concentrations, such as might be experienced in episodic emissions in the workplace. Studies with long-term exposure are used to assess potential adverse effects from continued exposure to low ambient concentrations. In addition, reproductive and developmental hazards are evaluated in several animal species. About ten chlorinated-, brominated-, and/or fluorinated-hydrogen-containing hydrocarbons, to be used alone or in combination, have been proposed as halon substitutes. In addition to health and safety, environmental, efficacy, and marketability considerations (Table I) need to be addressed for the selection of proposed halon substitutes. This presentation will discuss current EPA/Office of Air and Radiation thinking on a decision-tree approach for testing the toxicity of halon substitutes under the Significant New Alternatives Policy program. PMID- 8516766 TI - Application of kinetic models to estimate transit time through cell cycle compartments. AB - Models of the carcinogenesis process emphasize the importance of understanding cell cycle-specific effects of a chemical exposure. Development of mathematical models describing the kinetics of individual cell movements within the growth cycle are applied to a cultured cell system. Treatment with 100 micrograms/ml trichloroacetic acid is shown to retard transit through the synthesis phase of the cycle. The models are compared with standard relative movement calculations and are found to be more sensitive. In addition, the DNA compartments are modeled over time to detect possible development of aneuploidy during treatment. PMID- 8516767 TI - Developmental toxicity, reproductive toxicity, and neurotoxicity as regulatory endpoints. AB - For decades, cancer has been the primary toxicological endpoint used in the assessment of hazard and risk. Regulatory decisions related to the manufacture, transport, and use of a chemical are often based solely on cancer data. Federal policy is now shifting toward more frequent evaluation and application of alternative endpoints of toxicity. Among the endpoints of particular current interest are developmental toxicity, reproductive toxicity, and neurotoxicity. Significant progress has been made in the development of standardized guidelines for testing chemicals for their potential effects on these endpoints. Corresponding guidelines for the assessment of risk on the basis of data on these endpoints are in various stages of development. PMID- 8516768 TI - Neurobehavioral methods used in neurotoxicological research. AB - Exposure to chemicals in the environment and workplace can have adverse effects on the nervous system. Behavioral endpoints are being used with greater frequency in the hazard identification phase of neurotoxicology risk assessment. One reason behavioral procedures are used in animal neurotoxicology studies is that they evaluate neurobiological functions known to be affected in humans exposed to neurotoxic agents, including alterations in sensory, motor, autonomic, and cognitive function. In hazard identification, behavioral tests are used in a tiered-testing context. Tests in the first tier are designed to determine the presence of neurotoxicity. Examples of first-tier behavioral tests include functional observational batteries and motor activity. Second-tier tests are used to characterize neurotoxicant-induced effects on sensory, motor, and cognitive function. Second-tier tests are usually more complex and costly to perform. Reliance on behavioral endpoints in neurotoxicology risk assessment will likely increase in the future. PMID- 8516769 TI - Use of alternative endpoints with the UPitt II method for assessing the toxicity of smoke. AB - A small-scale combustion module and animal exposure system for evaluating flaming combustion and toxicity of smoke from burning polymers has been developed at the University of Pittsburgh and designated the UPitt II method. It is a radical departure from previous attempts to evaluate toxicity of smoke from burning polymers and represents a significant improvement over previous systems because well-defined burning conditions can be established over a wide range of imposed heat flux and ventilation levels, not possible to examine with previous methods. Thus, smoke toxicity can be evaluated under a range of burning conditions and differences in toxic potency and time to effect can be evaluated. A potential smoke hazard (PSH) index was developed which integrates the material performance characteristics which determine ease of ignition of a polymer with toxic potency, time to death, and rate of generation of toxicants. This paper describes sublethal endpoints that can be used with the UPitt II method and modifications to the PSH index for evaluating the toxicity of smoke generated by burning polymers. PMID- 8516770 TI - Industrial research on alternative fluorocarbons. AB - Fluorocarbons containing chlorine or bromine have been associated with stratospheric ozone depletion and the search for suitable alternatives is progressing at an accelerated pace. The Program for Alternative Fluorocarbon Toxicity Testing (PAFT), an international group representing most of the world's CFC producers, has been conducting comprehensive toxicological evaluations on several possible replacements for current fire-extinguishing agents--1,1-dichloro 2,2,2-trifluoroethane (HCFC-123), 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124), pentafluoroethane (HFC-125), and 1-fluoro-2,2,2-trifluoroethane (HFC-134a). Results from short-term experimental studies showing a low order of acute toxicity, as well as results from longer-term toxicity studies on these replacements, will be discussed. PMID- 8516771 TI - Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: novel animal models to study toxicant-induced epithelial transformation in airways. AB - Mucous (goblet) cell proliferation and hypersecretion of airway mucus are important characteristics of human respiratory disorders, especially chronic bronchitis and cystic fibrosis. These changes in secretory patterns also occur in animals experimentally exposed to chemical irritants such as ozone (O3), sulfur dioxide (SO2), and cigarette smoke. The cellular and molecular mechanisms involved in irritant-induced mucous cell metaplasia (MCM; transformation of airway epithelium, normally devoid of mucous cells, to a secretory epithelium containing numerous mucous cells) are still unclear. We used two experimental models of toxicant-induced MCM in rat airways to study the cellular and molecular changes that occur during the development of this respiratory tract lesion. MCM can be induced in the nasal transitional epithelium of rats by repeated exposure to ambient levels of ozone. In addition, MCM can be induced in the tracheobronchial airways of rats repeatedly exposed to endotoxin, a lipopolysaccharide-protein molecule found in the outer walls of Gram-negative bacteria. The pathogenesis of ozone- or endotoxin-induced MCM has been partially characterized using a variety of morphometric and histochemical techniques. Toxicant-induced changes in the numbers and types of airway epithelial cells have been estimated using morphometric methods designed for estimating the abundance of cell populations. Nasal pulmonary airway tissues are also processed for light microscopy and stained with Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) for detection of acidic and neutral mucosubstances (the specific glycoprotein product of mucous cells), respectively, within the tissue. Computerized image analysis is used to quantitate the amount of the stained mucous product within the airway epithelium. To better characterize the molecular and cellular events in the pathogenesis of ozone- or endotoxin-induced MCM in the rat airway epithelium, we are conducting studies to determine when, and in which epithelial cells, the mucin gene is expressed after exposure to the toxicant. In these studies, rats undergo single or repeated exposures to ozone or endotoxin and are then sacrificed immediately or a few days after the end of the exposures. Airway tissues are microdissected from specific regions of the exposed respiratory tract, and changes in mucin core polypeptide mRNA are evaluated by Northern analysis using human and rat mucin cDNA. In future studies using in situ hybridization, we will establish when, and in which epithelial cells, the expression of high molecular weight airway mucin is initiated in response to ozone or endotoxin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8516772 TI - Air Force approach to risk assessment for halon replacements. AB - Finding safe, environmentally acceptable, and effective replacements for Halon fire-extinguishing agents and other chemicals banned by the Montreal Protocol is a formidable task for Air Force research and development organizations. One factor that makes this task a challenge is the uncertainty in relating toxicology studies in laboratory animals to the human situation. This uncertainty from toxicology studies affects the risk assessment process by calling for very conservative decisions. Because of this uncertainty, public pressure and politics also impact the regulatory process. The Air Force approach to assessing health hazards for Halon replacements is to provide scientific information that directly applies to the parts of the extrapolation process that are responsible for the most uncertainty. Most regulatory agencies readily incorporate scientific information, when it is available, which can reduce uncertainty. These Air Force studies will be used to provide realistic exposure levels for replacement chemicals which will allow mission accomplishment and provide safety for the worker and the populace. PMID- 8516773 TI - Metabolism and pharmacokinetics of selected halon replacement candidates. AB - Metabolism studies were conducted using Fischer 344 and Sprague-Dawley rats following inhalation exposure to 1.0% (v/v) air atmospheres of 1,1-dichloro-2,2,2 trifluoroethane (HCFC-123), 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), 1 chloro-1,1-difluoroethane (HCFC-142b), bromochlorodifluoromethane (Halon 1211), and perfluorohexane (PFH) for 2 h. There were no remarkable differences in results between the two strains of rats. Animals exposed to HCFC-123 or HCFC-124 excreted trifluoroacetic acid in their urine. Urinary fluoride concentrations were increased in rats exposed to HCFC-124, and urinary bromide levels were increased in rats exposed to Halon 1211. Small quantities of volatile metabolites 2-chloro-1,1,1-trifluoroethane (HCFC-133a) and 2-chloro-1,1-difluoroethylene were observed in the livers of rats exposed to HCFC-123. Rats exposed to HCFC-142b excreted chlorodifluoroacetic acid in their urine; no volatile metabolites were detected in tissue samples. For PFH studies, no metabolites were detected in the urine or tissues of exposed animals. These results are consistent with proposed oxidative and reductive pathways of metabolism for these chemicals. Pharmacokinetic studies were carried out in rats exposed by inhalation to 1.0%, 0.1%, or 0.01% of HCFC-123. Following exposure, blood concentrations of HCFC-123 fell sharply, whereas trifluoroacetic acid levels rose for approx. 5 h and then declined gradually. Using a physiologically based pharmacokinetic model, saturation of HCFC-123 metabolism was estimated to occur at approx. 0.2% (2000 ppm) HCFC-123. PMID- 8516774 TI - Animal issues and society. AB - Animal use topics are sensitive issues today. Animal uses issues are often presented as black and white or 'we' are right and 'they' are wrong. This is clearly demonstrated in the available literature from most organizations. Topics presented will include: delineation of issues and concerned groups; examples of animal issues in education and agriculture; the terrorist issue; examples of animal issues/sportsman issues; examples of political and legislative impact; and examples of biomedical and toxicology animal use issues. PMID- 8516775 TI - Current DoD policy on use of animals in research. AB - The current Department of Defense (DoD) policy on use of animals in reseach is contained in the DoDD 3216.1 'The Use of Animals in DoD Programs' and its references. This Directive establishes DoD policy for the procurement, transportation, and care of animals used in research, development, testing and evaluation, clinical investigation, and instructional programs of the Department of Defense. This document lists the responsibilities of the Director of Defense Research and Engineering and the Heads of the DoD Components. In addition, it defines the specific responsibilities of the Secretary of the Army. This document will be discussed in some detail as the foundation for all research utilizing animals as test subjects throughout the Department of Defense. PMID- 8516776 TI - Formulation of ethical standards for use of animals in medical research. AB - In the past 200 years, moral theories and attitudes toward both humans and animals have changed considerably. These changes have led to widespread criticism of animal use in some or all research and testing. For the most part, the debate has been marked more by rhetoric than scholarship, but the underlying philosophical theories and their protagonists have been a very important influence on the modern debate over animal use. This paper examines some of the moral philosophy and attempts to present the main arguments concisely and simply and to refute common misconceptions. PMID- 8516777 TI - In vitro models for toxicological research and testing. AB - The objective of this report is to discuss some of the issues involved in utilizing in vitro methods in toxicological research and testing. The subject is not new, in vitro methods have been used for many years in this context. However, there has been a significant increase in interest in the topic within the scientific community recently as witnessed by the increase in scientific journals dedicated to the topic, symposia held by scientific societies, and commitment of resources to in vitro toxicological research activities. Toxicologists should be aware of these developments as the future directions of the science will be influenced significantly by in vitro methodology. PMID- 8516778 TI - In vitro methodologies for enhanced toxicity testing. AB - This report will give a general overview of some of the in vitro methodologies used in toxicity testing. The use of computer-based structure-activity relationships and cell culture testing systems can provide valuable toxicological data for hazard and risk assessments. In vitro systems allow for a more rapid identification of toxic compounds and can be utilized to study mechanisms of toxicity at the cellular and subcellular level. The data derived from these types of studies can be used to improve the predictability of animal models for chemical or drug toxicity. This report focused on primary hepatocytes as an in vitro model for cytotoxicity and metabolic studies. PMID- 8516779 TI - Effects of 2,4-dichlorophenoxyacetic acid on Rhizobium sp. growth and characterization of its transport. AB - The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) produced a deleterious effect on the growth of Rhizobium sp. M4, that was reversed by transferring the cells to a fresh control medium. The uptake of 2,4-D by Rhizobium sp. was not affected by chloramphenicol, indicating that it is constitutive rather than inducible. The mechanism of transport also appears to be energy independent, since uptake was not inhibited by azide or arsenate. PMID- 8516780 TI - Glutathione-dependent biotransformation of methyl parathion by mouse liver in vitro. AB - The present study was undertaken in an attempt to reconcile the seemingly conflicting observations that glutathione-dependent biotransformation of methyl parathion (O,O-dimethyl-O-(4-nitrophenyl)phosphorothionate) by hepatic supernatant or partially purified glutathione S-transferases occurs in vitro, but not to any significant degree in vivo in the mouse. While incubation of 20 microM methyl parathion with glutathione-fortified 100,000 x g hepatic supernatant resulted in biotransformation of this insecticide, addition of the carbon monoxide exposed microsomal fraction (without NADPH) to the supernatant abolished this metabolism. HPLC analyses of the distribution of methyl parathion between 100,000 x g supernatant and carbon monoxide-exposed microsomes revealed that little methyl parathion could be recovered in the 100,000 x g supernatant, and that the bulk of this insecticide was associated with the microsomal fraction. Increasing the concentration of methyl parathion to 1 mM resulted in a greater fraction of methyl parathion found in the supernatant compared to that with 20 microM, although the bulk of methyl parathion remained associated with the microsomal fraction. While this increase in the fraction of substrate located within the supernatant led to limited glutathione-dependent metabolism of methyl parathion, it must be emphasized that a liver concentration of 1 mM methyl parathion is far greater than that which could be achieved in vivo. In conclusion, the results of the present study support the hypothesis that in the mouse, glutathione-dependent metabolism of methyl parathion does not occur to a significant degree in vivo because of its limited access to the soluble glutathione S-transferases. PMID- 8516781 TI - Caffeine does not increase synthesis of heat shock proteins in rat embryos. AB - Caffeine exposure in utero in rats is known to result in intrauterine growth retardation and lowered birth weight as well as changes to behaviour and brain biochemistry. We have investigated whether caffeine's embryotoxicity is a result of the events associated with increased hsp synthesis, i.e., disruption to normal protein synthesis. Caffeine (30 mg/kg) was administered orally to pregnant rats as single or repeated doses. Embryos were removed 3 h after dosing on gestation day (GD) 9, 10, 11 and 12 and total embryonic protein and RNA analysed. There was no change in the mRNA or protein levels of hsp 88, 71/73, and 25 after acute or chronic treatment. To separate the direct effect of caffeine from those mediated through the mother, whole rat embryo culture was used. Caffeine (50 micrograms/ml) for 90 min did not increase hsp 88, 73 or 25 mRNA levels in 9.5, 10.5 and 11.5 GD cultured embryos. We conclude that in vivo or in vitro treatment of 9-12 GD rat embryos with moderate to high doses of caffeine does not increase the synthesis of the major mammalian hsps. Hence, hsp induction is unlikely to play a role in the embryotoxic actions of caffeine. PMID- 8516782 TI - Influence of chronic intoxication with selenium on collagen and elastin content in tissues of rat. AB - Rats were intoxicated with sodium selenite (0.3 mg/kg body wt.) for 10 weeks. An increase in total collagen content in skin and a decrease in the lungs, liver and kidneys were observed. Enhanced serum and urine levels of collagen metabolites were found. Elastin content was shown to be increased in the lung, liver, heart muscle and kidney of selenium-intoxicated rats. PMID- 8516783 TI - Effect of mancozeb on hepatic glutathione S-transferase in rat. AB - Oral administration of mancozeb (100 or 200 mg/kg body weight) for 7 consecutive days caused an increase in glutathione S-transferase (GST) activity in the liver of newborn, weanling and adult rats. This observed increase in GST activity was higher in weanling than in newborn and adult rats. Evaluation of acute effects at 4 and 20 h following oral administration of 200 mg mancozeb/kg showed a marginal increase in the levels of GST in adult rat liver. However, there was competitive inhibition of GST by the fungicide in vitro. PMID- 8516784 TI - Evidence that mercury from silver dental fillings may be an etiological factor in smoking. AB - The smoking habits of 119 subjects without silver/mercury dental fillings were compared to 115 subjects with amalgams. The amalgam group had 2.5-times more smokers per group than the non-amalgam group, which was highly significant. Because mercury decreases dopamine, serotonin, norepinephrine, and acetylcholine in the brain, and nicotine has just the opposite effect on these neurotransmitters, this may help explain why persons with dental amalgams smoke more than persons without amalgams. PMID- 8516785 TI - Effects of perinatal exposure to specific PCB congeners on thyroid hormone concentrations and thyroid histology in the rat. AB - Time-mated Sprague-Dawley rats were exposed to PCB 28 (2,4,4'-trichlorobiphenyl), 8 or 32 mg/kg/day; PCB 118 (2,3',4,4',5-pentachlorobiphenyl), 4 or 16 mg/kg/day; or PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), 16 or 64 mg/kg/day. At weaning, serum thyroxine (T4) was markedly depressed in pups, but not dams, exposed to PCB 118 or 153. Triiodothyronine (T3) was unchanged in pups and dams. In a histological evaluation of thyroids, the PCB 118 pups revealed changes suggestive of sustained TSH stimulation, including increased follicular cell vacuolization and height, increased nuclear vesiculation, and decreased colloid area. Decreases in body and brain weights and increases in liver weights were observed in some groups, with the high dose PCB 118 pups showing the greatest effect. PMID- 8516786 TI - Formation of methemoglobin by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H) furanone, MX, in rat erythrocytes in vitro. AB - Oxidative effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the principal bacterial mutagen in chlorinated drinking water were studied in rat erythrocytes. Upon incubation of rat blood with 14C-labelled MX (2 micrograms/ml), 42% of the radioactivity was found in plasma, 26% in erythrocyte cell membranes and 32% bound in hemoglobin. Although it was bound to hemoglobin, MX (1 mM) did not immediately affect the oxygen binding capacity of hemoglobin. MX (0.5 to 5 mM) decreased the portion of oxyhemoglobin and increased that of methemoglobin in erythrocytes suspended in buffer in a time- and concentration dependent fashion. In the same concentration range MX did not stimulate proteolysis nor did it cause hemolysis in erythrocytes. The results indicate that MX binds to hemoglobin and stimulates oxidation of hemoglobin in erythrocytes but MX does not cause overt oxidative damage to erythrocytes. PMID- 8516787 TI - Dose, dosimetry, and quality improvement of irradiated blood components. PMID- 8516788 TI - Identification of the blood component responsible for increased susceptibility to gut-derived infection. AB - It has previously been reported that the transfusion of allogeneic whole blood increases sepsis-related mortality and decreases the ability of the host to kill bacteria that have translocated from the intestinal tract. To determine which blood component contributes to this adverse effect, the impact of the transfusion of white cells (WBCs), red cells (RBCs), and plasma on microbial translocation, bacteria killing, and mortality rate was studied. Blood from C3H/HeJ mice was separated into WBCs, RBCs, and plasma, and these fractions were transfused to Balb/c mice. Controls received sterile saline. Five days after transfusion, all Balb/c mice underwent a 20-percent burn and gavage with 1 x 10(10) Escherichia coli labeled with 14C-glucose. Mortality was observed for 10 days. Four additional groups, receiving the same treatment as above, were sacrificed 4 hours after the burn, and mesenteric lymph nodes, liver, kidney, and blood were harvested aseptically. For each tissue, quantitative colony counts, radionuclide counts, and percentage of translocated bacteria that remained alive were calculated. By radionuclide counts, no difference was observed in the degree of 14C E. coli translocation among the groups. In contrast, the percentage of viable bacteria and the mortality rate were significantly higher in the group receiving allogeneic WBCs than in all other groups (p < 0.05). It is concluded that WBCs are the component in transfused blood that has an adverse effect on host resistance to gut-derived infection. PMID- 8516789 TI - Quantitation of immunoglobulin classes and subclasses of autoantibodies bound to red cells in patients with and without hemolysis. AB - The concentration of IgG, IgA, and IgM, as well as IgG subclasses, was measured by an enzyme-linked immunosorbent assay in autoantibodies eluted from red cells (RBCs); the number of molecules of each isotype per RBC was calculated. Three groups were analyzed: Group 1 included 23 patients with autoimmune hemolytic anemia (AIHA) associated with warm autoantibodies of IgG class; Group 2 included 11 patients without anemia but with a positive direct antiglobulin test (DAT); Group 3 included 10 healthy DAT-negative subjects. The mean number of IgG molecules per RBC in Group 1 (920) was about three times that in Group 2 (306) and about 17 times that in Group 3 (54). The range of RBC-bound IgG showed an overlap between the two groups of patients. The mean number of IgM and IgA molecules per RBC was low in the three groups. IgG1 predominated in all groups except in two patients with AIHA, in whom IgG3 made up at least 50 percent of total IgG. The mean number of IgG1, IgG2, and IgG4 molecules per RBC in Group 1 was about three times that in Group 2, whereas the mean number of IgG3 molecules per RBC was 10 times as high (p < 0.001). It follows that IgG3 was more common in patients of Group 1, but it was also detected in patients of Group 2. PMID- 8516790 TI - Predicting hemolytic disease of the newborn: a comparison of the monocyte monolayer assay and the chemiluminescence test. AB - The ability of the monocyte monolayer assay (MMA) and the chemiluminescence test (CLT) to predict the clinical significance of alloantibodies associated with hemolytic disease of the newborn (HDN) was assessed by the use of 22 well characterized antisera--predominantly anti-D--from alloimmunized pregnant women. Seventeen sera were obtained before delivery from women whose infants were antigen positive for the antibody specificities identified in the maternal serum. With testing of these 17 sera by MMA, 10 results were in agreement with the presence or absence of HDN, but there were 5 false-positive and 2 false-negative results. With the CLT, 16 results were in agreement with the presence or absence of HDN, and there was 1 false-negative result. Five sera were obtained from women whose infants were antigen negative for the antibody specificities identified in the maternal serum. The CLT and the MMA were both subject to false-positive results with these sera. These results suggest that the CLT may be more valuable than the MMA as a noninvasive test for predicting the clinical significance of alloantibodies in HDN. PMID- 8516791 TI - Laboratory tests to exclude IgA deficiency in the investigation of suspected anti IgA transfusion reactions. AB - Four methods were compared as to their suitability for excluding IgA deficiency in the investigation of suspected anti-IgA transfusion reactions. The methods were radial immunodiffusion, passive hemagglutination inhibition, sandwich enzyme linked immunosorbent assay, and membrane enzyme immunoassay. Parallel testing was performed on sera from 40 patients or blood donors previously found to have anti IgA and low or undetectable levels of IgA. All test methods identified the 40 sera as having abnormally low IgA levels. The membrane enzyme immunoassay required 10 minutes or less for testing, as compared to 3 hours for passive hemagglutination inhibition, 4 hours for sandwich enzyme-linked immunosorbent assay, and 48 hours for radial immunodiffusion. The membrane enzyme immunoassay offers the potential for a rapid, instrument-free screen of IgA levels and therefore may be useful in identifying those patients with suspected anti-IgA anaphylactic transfusion reactions who are not IgA deficient and do not require IgA-deficient blood components for additional transfusions. PMID- 8516792 TI - The effects of gamma irradiation versus white cell reduction on the mixed lymphocyte reaction. AB - The risk of transfusion-associated graft-versus-host disease (TA-GVHD) is related to the number of viable T cells transfused. Whether white cell (WBC)-reduced blood components would carry a decreased risk of TA-GVHD was considered, and the allogeneic mixed lymphocyte reaction was used as an in vitro model for TA-GVHD. An exponential decline in the mixed lymphocyte reaction was found to occur, as a result of either an arithmetic increase in the dose of gamma irradiation given to responding cells or a logarithmic decrease in the number of unirradiated responding cells. Irradiation of responding cells with 600 cGy or a 0.6 log10 reduction in the number of responding cells produced a 95-percent decline in the mixed lymphocyte reaction. Although these studies do not validate the use of WBC reduction as a substitute for gamma irradiation for the prevention of TA-GVHD, they suggest that the relative risk of TA-GVHD resulting from the use of standard cellular components versus WBC-reduced components merits further investigation. PMID- 8516794 TI - Time from diagnosis of acquired immune deficiency syndrome (AIDS) to death among persons with blood-borne AIDS in Italy. AB - The objective of the study reported here was to analyze survival time and factors associated with more rapid death among persons with acquired immune deficiency syndrome (AIDS) in Italy who acquired human immunodeficiency virus (HIV) infection through the transfusion of blood (n = 115) or blood components (n = 111). Subjects included all persons with AIDS all reported to the Italian AIDS Registry. The Kaplan-Meier method was used to estimate both the median survival time from the date of AIDS diagnosis to the date of death and the median survival time stratified by age at diagnosis, time of diagnosis, and AIDS-indicator disease. The Cox proportional-hazard model was used to assess factors independently associated with death. The prognosis for persons with blood-borne AIDS in Italy remains poor: overall median survival time was estimated to be 9.2 months, with no significant differences between hemophiliacs and transfusion recipients (p = 0.91). The median survival time for subject > 60 years old was 6.0 months, which is a significantly shorter time than that for younger subjects (p < 0.001). Subjects diagnosed prior to 1988 had a median survival time of 8.2 months, which is a significantly shorter time than that for subjects diagnosed after 1987 (p < 0.03). Subjects neurologically affected by AIDS had a median survival time of 4.1 months, which is a significantly shorter time than that for subjects diagnosed with any other disease (p = 0.03). Such factors were independently associated with more rapid death. PMID- 8516793 TI - Rapid freezing of whole blood or buffy coat samples for polymerase chain reaction and cell culture analysis: application to detection of human immunodeficiency virus in blood donor and recipient repositories. The Transfusion Safety Study Group. AB - Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it was decided to establish a cell repository of cryopreserved buffy coat (BC) samples, and thus far over 20,000 samples have been accumulated from enrolled subjects. To determine if these specimens could be used for polymerase chain reaction, a simple thawing and pelleting technique for recovering hemoglobin-free total white cells (WBCs) was developed. To validate the technique, parallel analysis was conducted of BCs, whole blood (WB), and PBMC samples from human immunodeficiency virus type 1 (HIV-1)-seropositive subjects. Immediate postthaw cell courts of 29 frozen-thawed (F-T) WB and BC samples averaged 90 percent of the prefreeze (input) values. Representative WBC populations were obtained by immediate pelleting. Amplification of HIV-1 gag sequences from F-T BCs and F-T WB was 94 and 75 percent, respectively, which is as sensitive as that obtained with freshly separated PBMC lysates. Quantitative HIV-1 proviral load analysis by serial dilution of 23 F-T BCs and 8 WB lysates showed results comparable to those obtained with lysates of fresh PBMCs. Values for WBC differential and immunophenotyping could be applied to express viral load relative to total WBCs, PBMCs, or CD4+ cells. These results establish the basis for simplified virologic analysis of cryopreserved BC or WB specimens. PMID- 8516795 TI - Stability of red cell antigens and plasma coagulation factors stored in a non diethylhexyl phthalate-plasticized container. AB - Red cell antigen stability studies were performed to evaluate whether the storage of red cells in plastic segments made up of a new non-di-2(ethylhexyl)phthalate (DEHP)-plasticized material resulted in poststorage antigenic reactivity different from that seen in segments made from DEHP-containing plastic. Serial 1 in-2 dilutions of commercially available antisera were prepared and tested by using stored red cells obtained from segments on Days 0, 28, 42, and, in some instances, 49. Antigenic determinants tested included A, B, D, c, K, Le(a), Fya, Jka, M, and P1. To minimize variability, the same reagent lots were used throughout each study, and the same technologists performed the assays in each laboratory. No significant differences in titration scores were seen when cells stored in segments made of the test plastic were compared with cells obtained from the same donor and stored for the same length of time in segments made of control plastic. In addition, plasma coagulation factor stability was studied in fresh-frozen plasma and cryoprecipitate stored for up to 1 year in the non-DEHP plasticized plastic containers. No significant differences were seen in prothrombin time, activated partial thromboplastin time, fibrinogen content, or factor V, VII, VIII, IX, or X activity as compared with plasma stored for equal periods of time in control plastic containers. It is concluded that the test plastic does not adversely affect red cell antigenic reactivity or plasma coagulation factor stability and that it is suitable for use in clinical transfusion practice. PMID- 8516796 TI - Effect of prestorage white cell reduction on bacterial growth in platelet concentrates. AB - Platelet concentrates stored with and without autologous white cells were produced from units of whole blood that had been purposefully contaminated with bacteria immediately after phlebotomy. The blood was inoculated with one of five species of bacterium at either 10 or 50 colony-forming units per mL. The growth of the organisms was quantified throughout the conventional 5-day, 22 degrees C storage period of the platelet concentrates. One species, Klebsiella pneumoniae, failed to grow in any of the components. The remaining species, Staphylococcus epidermidis, S. aureus, Enterococcus faecalis, and Salmonella enteritidis, achieved log growth after 1 day of storage and reached a relative maximum concentration by Day 3. Although the concentration of bacteria immediately after inoculation was lower in the units reduced in white cells by filtration, no significant differences were observed thereafter. Data from this in vitro study support the concept that prestorage white cell reduction of platelet concentrates should not increase the likelihood of transfusion-induced septicemia. PMID- 8516797 TI - Transfusion-associated graft-versus-host disease: report of an occurrence following the administration of irradiated blood. AB - Patients who are heavily immunosuppressed, such as those undergoing intensive anti-cancer chemotherapy, are at risk for development of accidental engraftment and graft-versus-host disease when they undergo transfusion with cellular blood components, a condition known as transfusion-associated graft-versus-host disease (TA-GVHD). To prevent this complication, it is routine to irradiate such blood components prior to their transfusion, although the minimum irradiation dose required is uncertain. The development of probable TA-GVHD is reported in a 10 year-old child following transfusions of platelets and packed red cells that had been irradiated at a nominal dose of 15 Gy. The transfusions were given during treatment for relapse of acute myeloid leukemia. Although the child developed complications including exfoliative dermatitis, delayed bone marrow regeneration, renal failure requiring dialysis, and respiratory failure requiring assisted respiration, she recovered from the episode of TA-GVHD after treatment with high dose methylprednisolone and antithymocyte globulin. However, her leukemia relapsed, and she died. This experience suggests that the irradiation of cellular blood components at a nominal dose of 15 Gy prior to their transfusion to heavily immunosuppressed patients may be insufficient to prevent TA-GVHD. PMID- 8516798 TI - White cell reduction and bacterial proliferation. PMID- 8516799 TI - Yersinia enterocolitica and blood transfusion. PMID- 8516800 TI - Abolition of the DVc subcategory. PMID- 8516801 TI - Complement-mediated bactericidal action and the removal of Yersinia enterocolitica by white cell filters. PMID- 8516802 TI - Effectiveness of white cell reduction by filtration with respect to blood storage time. PMID- 8516803 TI - Nitric oxide--a new endogenous immunomodulator. PMID- 8516804 TI - Selective intraportal hepatocyte transplantation in analbuminemic and Gunn rats. AB - Although significant progress has been achieved in isolated hepatocyte transplantation, the optimal site of cell implantation has not yet been determined. We have developed a novel experimental method of intraportal hepatocyte transplantation that allows easy assessment of the morphology and function of transplanted hepatocytes. Donor hepatocytes were harvested from Sprague-Dawley rats by in situ EDTA/collagenase perfusion. Fifteen recipient Nagase analbuminemic rats (NAR) underwent cannulation of the gastroduodenal vein under ether anesthesia. Either the posterior or anterior liver lobes were selectively infused with cells by occluding the portal venous supply of the nontransplanted liver lobes. Normal donor hepatocytes (2 x 10(7)) suspended in normal saline were infused over 1 min (4 ml). Recipients were treated with cyclosporine for the duration of the experiment. Plasma albumin levels were determined by ELISA, before and at various intervals after transplantation. In NAR rats transplanted with normal hepatocytes, there was a significant (P < 0.003) and sustained (12 weeks) increase in plasma albumin levels. Control NAR rats transplanted with NAR hepatocytes (n = 8) showed no significant changes in plasma albumin levels. Similarly, normal Wistar hepatocytes were infused intraportally into the posterior lobes of Gunn rats (n = 4), which lack the ability to conjugate bilirubin. Pre- and posttransplantation bile was collected following bile duct cannulation. Bile analysis by HPLC, demonstrated a significant (P = 0.04) increase in the level of bilirubin conjugates following transplantation and a corresponding decrease in total serum bilirubin (P = 0.04). Our experimental data demonstrate that direct selective intraportal infusion of hepatocytes is an effective technique of hepatocyte transplantation in the rat. PMID- 8516805 TI - The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney. AB - The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney are examined. Kidneys were transplanted from Munich Wistar (MW) rats to syngeneic controls and MHC-incompatible PVG strain recipients. We report on 4 groups of animals: (1) two-kidney control MW rats; (2) unilaterally nephrectomized MW rats (UNX); (3) renal transplantation from MHC identical MW littermates and removal of native kidneys (SYN); and (4) transplantation from MW donors to MHC-incompatible PVG rats and removal of native kidneys (ALLO). Glomerular filtration rate (GFR), single-nephron (SN)GFR, and glomerular capillary pressure (PGC) in SYN kidneys were depressed as compared to those in UNX (GFR, 1.41 +/- 0.08 vs. 0.80 +/- 0.08 ml/min; SNGFR, 67.2 +/- 4.8 vs. 44.7 +/- 6.6 nl/min; and PGC, 67 +/- 2 vs. 48 +/- 4 mmHg, UNX vs. SYN, respectively, P < 0.05). GFR and SNGFR in ALLO kidneys, however, were depressed even further (GFR, 0.40 +/- 0.05 ml/min; SNGFR, 13.8 +/- 1.8 nl/min; P < 0.05 for UNX vs. ALLO and SYN vs. ALLO). Afferent arteriolar resistance (RA) was increased greater than 4-fold (UNX, 1.01 +/- 0.15 10(10) dyn.sec.cm-5; SYN, 1.37 +/- 0.36 10(10) dyn.sec.cm-5; ALLO, 4.76 +/- 0.74 10(10) dyn.sec.cm-5 [P < 0.05, UNX vs. ALLO and SYN vs. ALLO]). This led to a precipitous fall in initial capillary flow rate in ALLO rats. These studies reveal the presence of moderate reductions in SNGFR and PGC in the nonrejecting transplanted kidney, which may relate to as yet unidentified consequences of the transplant surgery. More significantly, the principal mechanism leading to the reduced GFR characteristic of acute allograft rejection is identified as severe preglomerular vasoconstriction. PMID- 8516806 TI - Hyaluronic acid and purine nucleoside phosphorylase in vascular and luminal effluents of small bowel grafts as parameters of preservation injury. AB - Reliable parameters reflecting the degree of graft injury after small bowel preservation are currently not established. We investigated hyaluronic acid (HA) and purine nucleoside phosphorylase (PNP) as indicators of preservation injury before small bowel transplantation. In the first part of the study, intestinal grafts were harvested, perfused with saline, and flushed either immediately or after 1, 6, 12, 24, and 48 hr of cold storage (n = 6/group). HA and PNP were assayed in vascular and luminal effluents. In the second part of the study, 24 grafts were transplanted after preservation periods of 1, 6, 9, and 12 hr (n = 6/group) to assess if HA and PNP are predictors of postoperative graft survival. HA levels in vascular effluents and PNP activities in luminal effluents correlated with duration of preservation time and predicted graft survival. Utilizing both parameters significantly increased the predictive accuracy. PMID- 8516807 TI - Prevention of graft-versus-host disease in rat small bowel transplantation by recipient pretreatment with UV-B-modulated bone marrow cells. AB - UV-B irradiation (700 J/m2) of bone marrow cells (BMC) before transplantation into lethally irradiated (1050R) allogeneic rats prevents graft-versus-host disease (GVHD) and results in stable chimerism. This study examined whether UV-B modulation of BMT is useful in the subsequent induction of tolerance to small bowel transplant (SBT) and avoids the danger of GVHD, which remains the major obstacle to successful SBT. Lethally irradiated Lewis recipients of UV-B irradiated (700 J/m2) BMT (10(8) BMC admixed with 5 x 10(6) splenic leukocytes) either from ACI or Wistar-Furth (WF) rats developed stable chimerism without any evidence of GVHD for > 360 days. Lewis recipients of UV-B ACI BMC expressed 95 +/ 6% ACI lymphoid cells at 50 and 150 days after BMT using complement-dependent cytotoxicity assay. Unmodified Lewis recipients of orthotopic ACI SBT rejected their grafts and died in 7-9 days, whereas Lewis chimeras accepted permanently (> 200 days) bone marrow donor (ACI) SBT without any evidence of GVHD when the SBT was performed at 60 or 150 days after BMT. In contrast, when SBT was performed, only 30 days after induction of chimerism with UV-B ACI BMT, the recipients developed severe GVHD and died between 17 and 21 days. The Lewis chimeras rejected third part (WF) SBT acutely and died in 7-9 days, thus demonstrating the specificity of the induction of tolerance in this model. That this immunologic unresponsiveness is not restricted by the recipient-donor rat strain combination was shown by the permanent acceptance of WF SBT without GVHD by Lewis/WF chimeric recipients. Furthermore, the Lewis chimeras that were made diabetic with STZ 28 days after BMT permanently accepted (> 300 days) BM donor-type (WF) and recipient type (Lewis) islet cells and became normoglycemic, thus indicating tolerance to both donor and recipient Ags. The diabetic Lewis chimeras that became normoglycemic permanently accepted (> 200 days) WF SBT without any evidence of GVHD after donor-type SBT 110 days after WF islet transplantation. The apparent lack of organ-specific unresponsiveness in this model confirmed our previous observation with combined islet and heart transplants. In vitro MLR studies showed that the chimeric animals were specifically unreactive to donor- and recipient-type alloantigens. Our results demonstrate that UV-B irradiation of BMT is a promising approach to the induction of tolerance to SBT. PMID- 8516808 TI - Induction of nonspecific x-irradiation-resistant suppressor cell activity in vivo and prolongation of vascularized allograft survival by SK&F 105685, a novel immunomodulatory azaspirane. AB - SK&F 105685 is a novel azaspirane with immunosuppressive activity in animal models of autoimmune disease. This study evaluates the efficacy and mechanism of action of the compound in rat recipients of cardiac allografts. Short-term SK&F 105685 therapy (20 mg/kg/day by gavage) proved effective both in the pretreatment (days -14 to -8 or -7 to -1; allograft at day 0) and treatment (days 0 to 6) protocols, with cardiac allograft survival prolonged to 14-17 days (acute rejection = 7 days; P < 0.001). SK&F 105685 pretreatment exerted at least additive effects with subtherapeutic CsA (1.5 mg/kg/day x 7 days i.m.) given after transplantation, with 50% of allografts surviving > 50 days. SK&F 105685 therapy diminished the immunohistological features of acute rejection, with the cellular infiltrate suppressed and the induction of IL-2/transferrin receptors, and elaboration of IL-2/IFN-gamma essentially abolished, as compared with the grafts in untreated hosts. These correlated with normal frequency of CD4, CD5, CD8 phenotype subsets and B cells in recipient lymphoid organs, as shown by flow microfluorimetry. Adoptive transfer of untreated or x-irradiated (2000 rads) spleen cells from SK&F 105685-modulated hosts significantly prolonged the survival of donor-specific or third-party test cardiac allografts to 10-15 days, suggesting the presence of nonspecific x-irradiation-resistant suppressor cells in the transferred inoculum. Their activity could be enriched by Percoll density centrifugation and screened by the ability to inhibit Con A-driven proliferation of normal cells in the coculture assay. The light-density x-irradiation-resistant spleen cell fraction (1.07 g/ml) was consistently and significantly more suppressive than the heavy-density (1.09 g/ml) interface, or the corresponding unseparated cells. Thus SK&F 105685 therapy abrogates rejection response and significantly prolongs the survival of vascularized cardiac allografts in rats. This effect is associated with selective depression of host alloreactivity/immune activation at the graft site, and simultaneous induction of suppressor cells in recipient spleen, comparable to natural or nonspecific suppressor cells generated by TLI. This unique activity profile is consistent with the concept that SK&F 105685 should be considered as a critical chemical adjunct in novel therapeutic strategies representing TLI-equivalent. PMID- 8516809 TI - Studies of the use of L-leucyl-L-leucine methyl ester in canine allogeneic marrow transplantation. AB - L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is a lysosomotropic agent that selectively kills cytotoxic T cells and their precursors, natural killer cells, and monocytes but not helper T cells or other cells of hematopoietic origin. In this study, the effects of treatment of bone marrow and peripheral blood buffy coat with Leu-Leu-OMe on the outcome of allogeneic marrow transplantation were studied in several canine models. Whereas incubation of autologous marrow with Leu-Leu-OMe had no adverse effects on subsequent engraftment, incubation of marrow from dog leukocyte antigen (DLA)-identical littermates resulted in a high rate of graft failure. Previous studies have demonstrated that the addition of peripheral blood buffy coat allows engraftment of unrelated DLA-nonidentical marrow, and in this study we found that incubation of buffy coat with Leu-Leu-OMe did not alter this graft promoting effect. In a final experiment it was demonstrated that incubation of both marrow and peripheral blood buffy coat did not prevent the development of graft-versus-host disease in recipients of marrow from DLA-haploidentical littermates. In considering the eventual application of Leu-Leu-OMe in the clinic, these results are less encouraging than those previously reported using murine models. PMID- 8516810 TI - Lectin-dependent cell-mediated cytotoxicity and natural killer function in rejecting and infected lung allografts. AB - Differentiation between rejection and infection of lung allografts remains difficult. The effects of these two pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL) and PBL were investigated. Left lung allotransplantation was performed on 16 mongrel dogs of which 12 were available for complete studies. All animals received CA, AZA, and PRED for 2 weeks. Four grafts developed left lower lobe Gram negative pneumonia. The eight remaining recipients progressed gradually to severe rejection after acute reduction of immunosuppression. Cytolytic activity of blood and left lung BAL lymphocytes was quantitated by the natural killer (NK) and lectin-dependent cell-mediated cytotoxicity (LDCMC) assays. Two additional groups serving as controls were either given a 10-day course of immunosuppressants or had right lower lobe pneumonia induced by transbronchial inoculation of gram negative bacteria. Immunosuppressed control animals showed significant depression of PBL and BAL lymphocyte LDCMC and NK activity. Similarly, BAL lymphocytes expressed very low LDCMC in normal allografts (2.8 +/- 0.8%). Once rejection developed and progressed, LDCMC became significantly higher (15.6 +/- 2.2 and 52.7 +/- 2.8% in mild and severe rejection, respectively). There was no detectable NK activity in rejecting lung allografts. BAL lymphocytes from infected allografts, on the other hand, showed an elevation of both NK and LDCMC activity (9.1 +/- 1.1 and 14.6 +/- 1.0%, respectively). Similarly, bacterial pneumonia in control animals manifested an increase in NK and LDCMC activity in lung and blood. PBL lymphocytes of lung allograft recipients, however, had increased NK and LDCMC activity in both rejection and infection. LDCMC/NK activity ratio (LM/NK index) of lung lymphocytes was significantly higher in rejecting allografts (11.2 +/- 1.0 and 12.4 +/- 1.6 for mild and severe rejection, respectively) than in infected ones (1.2 +/- 0.3, P < 0.0001). It appears, from this study, that rejection of the lung allograft results in alterations in BAL lymphocyte phenotypes and functions that differ from those associated with bacterial infection. Such differences may be useful in distinguishing episodes of acute allograft rejection from bacterial infection. PMID- 8516811 TI - The effects of cyclosporine in Lewis rats with native and transplanted kidneys. AB - Several previous observations are consistent with the hypothesis that transplanted kidneys, because they are denervated, are protected from CsA-induced decreases in blood flow and glomerular filtration rate. The present experiments were designed to test this hypothesis, by using isogeneic Lewis rats as kidney donors and recipients. The recipients were unilaterally nephrectomized, such that each had one native and one transplanted kidney. Two to four weeks later, the insulin and PAH clearances of the two kidneys were measured and compared. CsA (10 mg kg-1 day-1) decreased inulin and PAH clearances, without affecting the PAH extraction. Thus, CsA decreased GFR and renal plasma flow. However, the decreases were not significantly different in native versus transplanted kidneys. Therefore, transplanted kidneys, at least in Lewis rats, are not protected from the adverse effects of CsA on renal hemodynamics. PMID- 8516812 TI - Platelet-activating factor in hepatic ischemia/reperfusion injury. The effects of a PAF antagonist combined with a prostaglandin I2 analogue. AB - The effects of TCV-309, a specific platelet-activating factor (PAF) antagonist, and OP-41483, a prostaglandin I2 analogue, on warm ischemia/reperfusion injury of the rat liver were studied. Rats were divided into five groups by the duration of warm ischemia and the treatment used. The NS1 group (normal saline pretreatment) had 60 min of warm ischemia, while the NS2 group (normal saline pretreatment), the PGI2 group (OP-41483, 500 ng/kg/min pretreatment), the TCV group (TCV-309, 3 micrograms/kg), and the PGI2+TCV group (both the above dosages) underwent 120 min of warm ischemia. Postoperative survival after 30 days, bile secretion, serum endotoxin levels, and tissue glutathione levels after 60 min of reperfusion were compared between the groups. The survival rates for the NS1, NS2, PGI2, TCV, and PGI2+TCV groups were 80%, 0%, 50%, 80%, and 86.7%, respectively. Bile secretion, which has a strong correlationship with hepatic cellular ATP level, was strongly correlated with survival. The NS2 group had a high serum endotoxin level- however, the PGI2 and PGI2+TCV groups had normal levels. Although there were some discrepancies between survival and the tissue glutathione level, combined treatment with the PGI2 analogue and TCV-309 was most effective in inhibited oxidative stress. In conclusion, TCV-309 increased the survival rate after 120 min of warm hepatic ischemia without endotoxemia by the PGI2 analogue. This finding suggest that warm ischemia/reperfusion injury is related to the generation of PAF. Combined pretreatment with TCV-309 and a PGI2 analogue may be useful in liver transplantation. PMID- 8516813 TI - Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation. AB - Chimerism was demonstrated with immunocytochemical and/or polymerase chain reaction techniques in kidney allografts and in the native skin, lymph nodes, or blood of 5 of 5 patients who received continuously functioning renal transplants from 1 or 2 haplotype HLA mismatched consanguineous donors (4 parents, 1 aunt) 27 29 years ago. In the 4 cases where the kidney donor still was alive to provide stimulator lymphocytes for testing, these provoked no (n = 2) or modest (n = 2) MLR in contrast to vigorous MLR to third party lymphocytes. In all 4 cases, the donor cells failed to generate in vitro cytotoxic effector cells (cell-mediated lymphocytotoxicity). These findings are in accord with the hypothesis that cell migration, repopulation, and chimerism are seminal events that define graft acceptance and ultimately can lead to acquired donor-specific nonresponsiveness (tolerance). PMID- 8516814 TI - Hepatitis C is a poor prognostic indicator in black kidney transplant recipients. AB - BACKGROUND: The significance of hepatitis C in kidney transplant recipients is unclear. The prevalence of antibodies to hepatitis C among candidates for transplantation is up to 50% in some centers. METHODS: We screened 640 frozen serum samples obtained pretransplantation from all kidney recipients at the Medical College of Wisconsin between January 1979 and March 1990 for antibody to hepatitis C using the second generation immunoassay. Charts were reviewed from all hepatitis C antibody-positive (anti-HCV+) patients and 256 randomly chosen hepatitis C antibody negative (anti-HCV-) controls. Actuarial patient and graft survival in these two groups were determined. RESULTS: The prevalence of anti-HCV was 8.3%. Blacks and i.v. drug users were disproportionately represented in the anti-HCV+ group. Of the anti-HCV+ patients, 18.9% developed chronic hepatitis independent of race. Black anti-HCV+ patients had a 5-year graft survival of 28 +/- 11% compared to 67 +/- 7% in black anti-HCV- patients (P = 0.003). Black anti HCV-, white anti-HCV-, and white anti-HCV+ patients all had similar graft survival. Anti-HCV was not a poor prognostic indicator for overall patient survival or the development of aplastic anemia and malignancies including hepatocellular carcinoma. CONCLUSIONS: Anti-HCV is a significant risk factor for reduced kidney graft survival in blacks apart from i.v. drug abuse. Black anti HCV- patients had graft survival similar to white transplant recipients, indicating that anti-HCV may be one marker for the poorer graft survival in blacks that has been observed in most transplant programs. Anti-HCV in kidney transplant recipients increases the risk for the development of chronic hepatitis post-transplant. PMID- 8516815 TI - The clinical significance of allospecific antibodies against endothelial cells detected with an antibody-dependent cellular cytotoxicity assay for vascular rejection and graft loss after renal transplantation. AB - Serum samples of 64 consecutive patients who underwent renal transplantation in our institution were examined for the presence of antibody-dependent cellular cytotoxicity (ADCC) activity against endothelial cells (EC). From each patient serum samples were obtained immediately before transplantation and 1 week, 1 month and 1 year thereafter. The results were evaluated in the context of tests to measure donor-specific humoral immunity against lymphocytes and monocytes, and related to parameters of presensitization, graft survival, and histology. Sera from 10 patients were positive for ADCC on a panel of HLA-typed endothelial cells. In 8 patients sera were already positive before transplantation and remained positive thereafter. In 4 patients a positive crossmatch with donor T and B cells and monocytes could be observed after transplantation. In only one patient were these crossmatches positive before transplantation. A significant correlation was found between ADCC positivity and vascular rejection (P = 0.015); in addition graft survival was significantly better in the ADCC negative group vs. the positive group (P = 0.0004). These data demonstrate the significance of allospecific anti EC antibodies for the occurrence of vascular rejection and graft loss after renal transplantation. PMID- 8516816 TI - HLA-DRB1 matching as a recipient selection criterion in cadaveric renal transplantation. AB - We retrospectively examined the effect of HLA-DRB1 matching at the DNA level compared with serological HLA-DR matching on acute rejection and graft survival in patients who underwent primary cadaveric renal transplantation. For patients with serological HLA-DR zero mismatch, the incidence of acute rejection in patients with zero DRB1 mismatch (3/20; 15%) was significantly lower than in those with one or two DRB1 mismatches (10/21; 48%). Five-year graft survival in patients with zero DRB1 mismatch was 100%, whereas that in those with one or two DRB1 mismatches was 76%, although the difference was not statistically significant. The fact that HLA-DRB1 matching at the DNA level influenced incidence of graft rejection after cadaveric renal transplantation is analogous to results in living-related renal transplantation. It is suggested that avoidance of mismatching for DRB1 alleles at the DNA level in recipient selection of cadaveric renal transplantation leads to an improvement of graft outcome. PMID- 8516817 TI - Immunosuppressive therapy as a determinant of transplantation outcomes. AB - Although surgical proficiency is essential to the immediate outcome of transplantation, long-term success depends upon how adequately the transplantation recipient is managed. Immunosuppression, the most critical aspect of after care, is subject to wide variation. In January 1990, a survey was sent to the directors of all transplant programs in the United States performing one or more kidney, heart, liver, heart-lung, or pancreas transplant in 1988. Detailed data were obtained on both the drugs and methods used for induction and maintenance immunosuppression, as well as the treatment of rejection. Each program director was asked to rank each immunosuppressive approach according to its perceived impact on patient outcomes. Over 85% of all eligible program directors completed the survey. There is no evidence of survey respondent bias. The use of polyclonal and monoclonal agents for induction immunosuppression was favored most by pancreas program directors (72-76%). These agents were least preferred by liver transplant programs (35-37%). About half of kidney, heart, and heart-lung program directors preferred these agents. Triple-drug therapy consisting of CsA, PRED, and AZA was considered the most preferable maintenance protocol for all transplants (i.e., kidney, 89%; heart, 94%; liver, 88%; heart lung, 86%; pancreas, 96%). Either i.v. steroids or OKT3 were regarded as the preferred approaches for the treatment of acute or resistant rejection. Finally, the acceptability of outpatient treatment of rejection varied by transplant type (i.e., kidney, 9%; heart, 58%; liver, 5%; heart-lung, 29%; pancreas, 8%). Although there are similarities in the ratings of various aspects of immunosuppressive therapy, there are important differences. This information is critical to anticipate the implications of new immunosuppressive agents and to evaluate changes in the use of existing drugs and therapeutic approaches. PMID- 8516818 TI - Arterial ketone body ratio and glucose administration as an energy substrate in relation to changes in ketone body concentration after living-related liver transplantation in children. AB - Changes in the arterial ketone body ratio (AKBR [acetoacetate/3 hydroxybutyrate]), which reflect the redox state of the liver mitochondria (NAD+/NADH), as well as those in total ketone body concentration (TKB) and blood glucose level were studied in 30 living-related liver transplantations (LRLT) performed in pediatric patients at Kyoto University Hospital from June 1990 to January 1992. AKBR increased to over 1.0 within 6 hr after reperfusion of the graft in 11 cases (37%), within 12 hr in 7 (23%), on POD 1 in 8 (27%), and on POD 2 in the remaining 4 cases (13%). TKB significantly increased while AKBR remained below 0.7 (266 +/- 40 mumol/L), but it significantly decreased in accordance with the recovery of AKBR above 1.0 (61 +/- 6 mumol/L). This indicates the change in the predominant energy substrate for hepatic mitochondria from fatty acid to glucose during the AKBR recovery process. In 6 cases, the AKBR transiently decreased to below 1.0 after initial recovery concomitant with the fall in blood glucose level and the increase in TKB. However, the AKBR was rapidly restored to over 1.0 again immediately after the glucose administration was increased. This suggests that glucose administration to maintain blood glucose level between 150 and 250 mg/dl is essential for the AKBR recovery above 1.0 that accompanies the normalization of graft metabolic functions, and that, along with the postoperative minimal increase in serum enzymes and favorable outcome of the transplant with no incidence of a primary nonfunctioning graft, the prompt and successful recovery of AKBR reflects the expected high viability of the graft in our LRLT cases. PMID- 8516819 TI - Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody. AB - Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past. The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL 2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation. In two groups of 33 patients each, postoperative survival, graft biopsies, liver function enzymes, and the clinical courses after OLT were evaluated. Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT. Furthermore, our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody. This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation. PMID- 8516821 TI - Suppression of synthesis of natural antibodies by mycophenolate mofetil (RS 61443). Its potential use in discordant xenografting. AB - One of the major barriers to successful transplantation of immediately vascularized organs between discordant species is the presence of natural antibodies (NA) in the recipient. While natural antibodies can be depleted by plasmapheresis and/or organ absorption, they rapidly return to the circulation after such procedures. It will be desirable to suppress NA for longer periods of time. Since NA appear to be produced at least in part by CD5+ B cells, it was important to evaluate whether mycophenolate mofetil (RS-61443), a novel immunosuppressant that has been shown to suppress normally elicited antibody synthesis, would also be able to suppress NA. Adult rats were splenectomized, and 2 days later, 9 plasma exchanges, each of 4 ml, were performed. One group of rats received RS-61443 at 40 mg/kg/day (the dose described as efficacious for suppressing elicited antibodies in rats) starting immediately after the last exchange for 7 days, and then 20 mg/kg/day for an additional 7 days; no drug was given to the control group. NA levels were measured at various times by ELISA, using guinea pig platelets extracts as the target. Splenectomy alone led to a significant decrease from the control levels of NA; titers were further reduced by the plasma exchanges. In the absence of RS-61443, NA titers rose steadily, starting at 24 hr after the last plasma exchange. In contrast, administration of RS-61443 resulted in levels of NA on day 7 not significantly different from those after plasma exchange, reducing the dose of RS-61443 to the 20 mg/kg/day level during week 2 allowed the gradual return of NA. Administration of RS-61443 at the 40 mg/kg/day dose to rats after splenectomy alone led to a clear and significant further decrease in NA levels over the first week. It has been shown that RS 61443 can be administered for longer periods. The data presented suggest that use of this drug, perhaps with more conventional agents, may allow suppression of NA for a significant period after transplantation. PMID- 8516820 TI - Increased hyaluronan in acutely rejecting human kidney grafts. AB - The glycosaminoglycan hyaluronan is not only involved in cellular differentiation and migration but may also play a role in several inflammatory diseases. We have previously demonstrated an increased local production of hyaluronan in chronically rejected kidneys and the correspondingly affected renal vessels. In this report, we demonstrate the presence of hyaluronan in acutely rejecting kidneys. A total of 77 biopsies classified as either acute rejection or nonrejecting were analyzed using a biotin-labeled hyaluronan-binding protein in conjunction with an avidin-biotin peroxidase detection system and graded using an arbitrary scale from 0 to 3. Those biopsies classified as nonrejecting did not contain any peritubular hyaluronan in the cortex, with hyaluronan being localized only in the medulla. In contrast, those biopsies exhibiting acute rejection had an increase of hyaluronan both in the cortex and in the medulla. This increase was significantly different (P = 0.0001) and correlated with edema and interstitial inflammation. The detection of the local hyaluronan production may be a useful marker to measure acute rejection episodes. PMID- 8516822 TI - Removal of natural human xenoantibodies to pig vascular endothelium by perfusion of blood through pig kidneys and livers. AB - We have examined the nature of the binding of human xenoantibodies to pig liver and kidney vascular endothelium. Our results demonstrate that human serum contains IgM and IgG xenoantibodies that bind to pig vascular endothelium, and that the pattern of antibody binding is similar for both livers and kidneys. Immunohistochemical analysis of pig kidneys after perfusion with human blood demonstrated the binding of both IgM and IgG xenoantibodies, complement (C3), and fibrinogen to the vascular and glomerular endothelium. An ELISA assay of the perfusate after perfusion of 500 ml of human blood through a single pig kidney for 60 min demonstrated a significant reduction in the amount of human IgM (67%) and IgG (55%) binding to pig aortic endothelium. Similar perfusion experiments conducted with pig livers were associated with minimal immunohistochemical evidence of the binding of human xenoantibodies to liver vascular endothelium. Immunofluorescence staining for IgM, IgA, C3, and C1q was negative or minimally positive in the liver vascular endothelium. Sinusoidal endothelium were weakly positive for IgG and fibrinogen. The perfusion of the pig liver with human blood was, however, associated with a significant reduction in the subsequent binding of IgM and IgG to pig kidney vascular endothelium. Pig liver perfusion was also responsible for the removal of both IgM and IgG xenoantibodies capable of reacting with pig aortic endothelium, as measured by an ELISA assay of the perfusate. These results suggest that both pig kidney and livers are capable of absorbing the xenoantibodies that may be responsible for mediating a hyperacute rejection of pig xenografts and that the distribution of the target antigens for these antibodies is similar in the two organs. PMID- 8516823 TI - Changes in the immune response against BCP 54 following corneal transplantation in man. AB - Bovine corneal protein (BCP) 54 is the major soluble protein of the cornea. Immune responses against this protein can be observed in patients with corneal disease or inflammatory disease of the anterior chamber of the eye. We wanted to determine whether an immune response against this corneal protein plays a role in corneal transplantation. A cell-mediated immune response against BCP 54 was therefore determined in 46 patients prior to and on several occasions during the first year following corneal transplantation. The presence of an anti-BCP 54 response before transplantation was not associated with any clinical parameters or with rejection following transplantation. The highest frequency of positive responses was observed three months after transplantation. Transplantation may have stimulated a temporary immune response against a previously sequestered antigen, but this tissue-specific immune response did not necessarily lead to rejection. Therefore, no prognostic value can be attributed to the anti-BCP 54 response. PMID- 8516824 TI - Induction of donor-specific unresponsiveness to rat cardiac allografts by intrathymic injection of UV-B-irradiated donor spleen cells. AB - This study examined the role of intrathymic injection of allogeneic spleen cells in induction of donor-specific unresponsiveness to heart allografts in the Lewis to-ACI rat combination. Intrathymic injection of naive Lewis SC led to rejection in naive or sublethally irradiated (200 rads TBI) ACI recipients at times equivalent to those obtained in control animals. Intrathymic injection of UV-B irradiated Lewis SC, on the other hand, led to indefinite cardiac allograft survival (> 300 days) in sublethally irradiated ACI recipients; similar treatment failed to prevent rejection of third-party (Wistar Furth) cardiac allografts, which demonstrates the specificity of the immunologic unresponsiveness thus induced. The finding that intrathymic injection of untreated allogeneic SC does not prevent rejection of subsequently transplanted allograft suggests that modulation of major histocompatibility complex class II molecule by methods such as UVB may be critical to induction of unresponsiveness. Inoculation of UV-B donor SC in extrathymic sites (subcutaneous, intraperitoneal and intratesticular) did not significantly prolong graft survival in similarly prepared animals, thus confirming the privileged position of the thymus in the induction of tolerance. When the unresponsive recipients of cardiac allografts were made diabetic at 100 days and rechallenged with a second-set donor-type neovascularized pancreatic islet grafts, three of four animals accepted permanently (> 100 days) the islet grafts, thus indicating tolerance to donor alloantigens. To define the underlying mechanisms of specific tolerance in this model, in vitro MLR and in vivo adoptive transfer studies failed to demonstrate suppressor activity in the long-term cardiac allograft recipients. In contrast CML assays using 51Cr-release showed that T cells obtained from the unresponsive animals had no detectable cytotoxic activity to Con A-stimulated donor blast targets. The latter finding suggests clonal anergy or deletion of cytotoxic T cells to donor alloantigens. Our results confirm the role of the thymus as a privileged site for the induction and maintenance of specific immunologic unresponsiveness to organ allografts and suggest that this approach may be potentially useful in clinical transplantation of immediately vascularized allografts and neovascularized grafts. PMID- 8516825 TI - Induction of donor-specific unresponsiveness to rat cardiac allografts by pretreatment with intrathymic donor MHC class I antigens. AB - Since intrathymic injection of UV-B-irradiated spleen cells induces donor specific unresponsiveness in the sublethally irradiated (200 rads TBI) recipients, while intrathymic injection of naive SC leads to acute graft rejection, we hypothesized that presentation of MHC class I rather than MHC class II antigens to immature T cells in the thymus may convey a tolerogenic signal to the recipient. The present study was designed to examine if intrathymic injection of naive MHC class I-positive resting T lymphocytes can induce antigen-specific unresponsiveness to cardiac allografts in the Lewis-to-ACI rat combination. The results showed that intrathymic injection of resting Lewis T cells consistently induced indefinite graft survival (> 300 days) in sublethally irradiated (200 rads TBI) ACI recipients while similar treatment failed to prevent the rejection of third-party (Wistar-Furth) cardiac allografts, thus demonstrating the specificity of the immunologic unresponsiveness to donor alloantigens. Examination of the timing of intrathymic antigen presentation relative to cardiac transplantation that would achieve 100% permanent graft survival in the Lewis-to ACI rat combination showed that the optimal time was 7 days before allografting, while peritransplant and immediate post-transplant intrathymic inoculation of donor T cells was relatively ineffective in the induction of unresponsiveness to donor grafts. We also showed that removal of the antigen-containing thymus in the sublethally irradiated recipients with functioning cardiac allografts consistently caused graft rejection if performed earlier than 21 days after heart transplantation; thymectomy after 21 days of organ transplantation did not affect indefinite survival of the grafts. Thus, it appears that the maintenance of peripheral tolerance to the grafts after 21 days of transplantation may be dependent on the presence of a new clone of antigen-specific tolerant host T cells. These results confirm the immunologic privileged position of the thymus in the induction of central and peripheral tolerance, and suggest that pretreatment with intrathymic MHC class I alloantigens is potentially useful in the induction of unresponsiveness to donor vascularized allografts in adult animals and in man. PMID- 8516827 TI - Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels. AB - The effect of rapamycin (RPM) on the extent of arterial intimal thickening was determined in rat recipients of orthotopic femoral artery allografts or in rats that had undergone balloon catheter injury to carotid arteries. In untreated rats, neointima comprised approximately 50% of the arterial wall area in both models. Although treatment of allograft recipients for 40 days with 1.5 mg/kg/day RPM was ineffective, a dose of 6 mg/kg/day (days 0-7) followed by 3 mg/kg/day (days 8-39) reduced intimal thickening by 98% (P < 0.0001). The higher RPM dose reduced T cell and macrophage infiltration significantly and decreased the expression of IL-2 receptor, class II Ag, and mRNAs for growth factors and cytokines. Treatment with 1.5 mg/kg/day RPM (days 0-13) after balloon-catheter injury reduced intimal thickening by 45% (P = 0.0254) and substantially decreased macrophage infiltration and expression of class II Ag in the adventitia. Within the neointima, however, mRNAs for platelet-derived growth factor-alpha, basic fibroblast growth factor, and transforming growth factor-beta were still expressed. In summary, we have shown that RPM inhibits not only the vascular response to injury caused by allograft rejection, but also the response to balloon catheter injury. This new information is important to our understanding of: (1) the fundamental processes responsible for intimal thickening regardless of the cause of vascular injury, (2) mechanisms of action of RPM that explain its effects on the response to very different types of vascular injury, and (3) the potentially diverse therapeutic applications of drugs, like RPM, that inhibit the actions of both immune and nonimmune cytokines and growth factors. PMID- 8516826 TI - Induction of natural suppressor-like cells from human adult peripheral blood lymphocytes by a K562-derived factor. AB - K562-AC1, a subclone of the human myeloid leukemia cell line K562, secreted an inhibitor of PHA-stimulated human T cell growth into the culture supernatant (K562sup). Kinetics and absorption assays in vitro revealed that the factor acts on PBMC during the very early growth phase. PBMC gained potent suppressor activity against autologous T cell growth after preculture with K562sup for 3 days in a dose-related manner. HLA class II negative and nylon wool-nonadherent subsets possessed higher suppressor potential than unfractionated PBMC. Treatment of K562sup-precultured PBMC with mAb followed by complement-lysing showed that the responsible suppressors belong to null cells expressing CD3-, CD4-, CD19-, CD14-, CD11b-, but partially CD2+. Exogenous IL-2 exhibited a synergistic effect on the activity of the suppressors committed by K562sup. However, K562sup inhibited IL-2-activated lymphocytes from generating anti-K562 cytolytic activity. Macrophages inhibited the induction of the suppressors, which was restored by adding indomethacin and/or IL-2. In conclusion, K562sup has the ability to induce efficient suppressor cells from human adult PBL, which belong to null cells without NK/lymphocyte-activated killer activity and are similar to natural suppressor cells. PMID- 8516828 TI - Xenotransplantation: baboons as potential liver donors? Scientific and ethical issues. AB - The dramatic development of liver transplantation compared to a relative shortage of donors has brought a renewed interest to xenotransplantation. Because of anatomical and immunological compatibilities, nonhuman primates are the most appropriate donors. The aim of this work was to analyze the different problems of a baboon-to-man liver xenotransplantation. Thirty baboons bred in a French Primatology Center were studied. The analysis of anatomical, microbiological, and immunological data showed that only 8 baboons out of 30 were suitable as donors for xenotransplantation. Considering these data and the ethical issues, the actual feasibility of xenotransplantation programs is discussed. PMID- 8516829 TI - Markers of coccidioidomycosis before cardiac or renal transplantation and the risk of recurrent infection. PMID- 8516830 TI - Pretransplant platelet transfusions: their effects on renal allograft outcome and mixed lymphocyte culture reactivity. PMID- 8516831 TI - Reactivation of experimental chronic T cruzi infection after immunosuppressive treatment by cyclosporine A and betametasone. PMID- 8516832 TI - Multiorgan procurement from a victim of cyanide poisoning. A case report and review of the literature. PMID- 8516833 TI - Failure of azathioprine and steroids to augment one-day-pretransplant donor specific transfusion-enhanced allograft survival. PMID- 8516834 TI - The effect of the platelet-activating factor inhibitor TCV-309 on reperfusion injury in a canine model of ischemic lung. PMID- 8516835 TI - Immunosuppression mediated by heat-treated cells. Suppression or anergy? PMID- 8516836 TI - Triiodothyronine treatment in brain-dead multiorgan donors--a controlled study. PMID- 8516837 TI - 1D-->4D. PMID- 8516838 TI - Genetics in the post-sequence era. PMID- 8516839 TI - Molecular medicine--towards the millennium. PMID- 8516840 TI - Coming of age. PMID- 8516841 TI - Thoughts on genetics at the fin de siecle. PMID- 8516842 TI - Genetics at the millennium. PMID- 8516843 TI - In vivo, in vitro, in silicio: towards a virtual cell. PMID- 8516844 TI - Animal models of human genetic diseases. AB - Gene targeting in cultured embryonic stem cells permits the generation of mice with a desired alteration in a chosen target gene. Application of this procedure to create mouse models of human diseases is revealing the innate complexity of diseases normally ascribed to single gene defects. Modeling human diseases that are known to be multigenic in origin and are markedly influenced by environmental factors is potentially even more revealing. PMID- 8516845 TI - Genomic structure and function in the MHC. AB - The major histocompatibility complex (MHC) is a fascinating region of the human genome. More is known about this 4 Mb of DNA (0.1% of the genome) on the short arm of chromosome 6 than about any other region of similar size. Among the 80 or so MHC genes found so far are several clusters with related functions in antigen processing and presentation. In addition to its importance in immunology, the MHC is a useful model for investigating gene organization, polymorphism, linkage disequilibrium and recombination. A large number of diseases, many of the autoimmune type, are associated with the region. PMID- 8516846 TI - Epigenetic inheritance in mammals. AB - The epigenetic phenomena of genome imprinting and X-chromosome inactivation, found in mammals, both entail homologous genes or chromosomes behaving differently within the same cell. Although both have consequences for genic balance in the whole genome, in imprinting the control seems mainly at the single gene level, whereas in X-chromosome inactivation there is coordinated regulation of the whole chromosome, and single gene effects are relatively minor. PMID- 8516847 TI - Mitochondrial diseases: genotype versus phenotype. AB - Recently, a variety of degenerative diseases have been attributed to mutations in mitochondrial DNA. Even though these mutations are inherited and present throughout the body, they frequently cause late-onset, tissue-specific disease. This may be explained by a combination of the tissue-specific accumulation of somatic mtDNA mutations with age and the variation between tissues in the expression of nuclear genes that encode mitochondrial functions. PMID- 8516848 TI - Transcriptional regulation of multigene loci: multilevel control. AB - Recent studies indicate that different levels of control operate within multigene loci. In addition to regulatory sequences immediately flanking the genes, there are also elements that act over long distances on more than one gene. Competition for these elements among genes can influence both the level and timing of gene expression during development. PMID- 8516849 TI - The multistep nature of cancer. AB - Cancer is a distinct type of genetic disease in which not one, but several, mutations are required. Each mutation drives a wave of cellular multiplication associated with gradual increases in tumor size, disorganization and malignancy. Three to six such mutations appear to be required to complete this process. PMID- 8516851 TI - Trends in genetics--a logical development (reprise). PMID- 8516850 TI - Human chromosome 21: genome mapping and exploration, circa 1993. AB - Chromosome 21 is the smallest human chromosome, but one of considerable medical importance. A comprehensive physical map of overlapping YACs, a dense linkage map and an almost complete long-range restriction map have been produced much earlier than expected. These mapping accomplishments will greatly facilitate the exploration of chromosome 21, helping to characterize both genes and their impact in health and disease. PMID- 8516852 TI - Renal transplantation and autosomal dominant polycystic kidney disease: 20 years' experience. PMID- 8516853 TI - Outcome of live-related donor renal transplants in their second decade. PMID- 8516854 TI - Kidney transplantation in the pediatric age group: university of Miami experience. PMID- 8516855 TI - Short- and long-term results with en bloc transplantation of pediatric kidneys into adults. PMID- 8516856 TI - Transplantation of single pediatric cadaveric kidneys into adult recipients. PMID- 8516857 TI - Renal transplantation in patients with systemic lupus erythematosus. PMID- 8516858 TI - Kidney transplantation in children. PMID- 8516859 TI - Rapidly progressive focal segmental glomerulosclerosis occurring in a living related kidney transplant donor: case report and review of 21 cases of kidney transplants for primary FSGS. PMID- 8516860 TI - Dyslipidemia in renal transplantation: a 3-year follow-up. PMID- 8516861 TI - Influence of donor age and rejection episodes on renal allograft outcome. PMID- 8516862 TI - Effect of donor age on graft function and graft survival in cadaver renal transplantation. PMID- 8516863 TI - Is it worth it to use kidneys between spouses? PMID- 8516864 TI - Beneficial effects of verapamil in renal transplantation. PMID- 8516865 TI - Pregnancy and kidney transplantation: clinical problems and experience. PMID- 8516866 TI - Chromosomal aberrations among offspring of female renal transplant recipients. PMID- 8516867 TI - Recent developments in liver transplantation. AB - The many developments that have occurred and continue to occur have also meant that the quality of life experienced by recipients of a successful graft is excellent, with more than 85% of patients returning to normal life and work (even having children). While long-term survival still occurs more frequently in favorable groups such as children with metabolic abnormalities or biliary atresia, results are still extremely good for adults, with 3-year survival figures after transplantation for cirrhosis in the order of 75%. These figures also continue to improve, and with the skill and enthusiasm that workers in this field display they seem destined to continue unabated. PMID- 8516868 TI - Clinical intestinal transplantation. PMID- 8516869 TI - An update of partial liver transplantation. PMID- 8516870 TI - Segmental living related donor liver transplantation in childhood. PMID- 8516871 TI - Liver transplantation at the University of Alberta Hospitals: a review of the first three years. PMID- 8516872 TI - Live donor segmental hepatectomy in liver transplantation. PMID- 8516873 TI - Combined liver-kidney transplantation from a living-related donor. PMID- 8516874 TI - Comprehensive evaluation of brain-dead donors for liver transplantation: personal experience. PMID- 8516875 TI - Arterial variations in 13 living liver donors. PMID- 8516877 TI - Heart transplantation in 1992: the La Pitie experience. PMID- 8516876 TI - Cerebrospinal fluid examination as a possible predictor of neurological outcome in patients with acute liver failure. PMID- 8516878 TI - Comparison of blood-based and crystalloid cardiopneumoplegic solutions in heart and lung preservation for 24 hours: an ultrastructural morphometric study in dogs. PMID- 8516879 TI - Evolution of glomerular filtration rate and renal plasma flow in cyclosporine treated heart transplant recipients over a 1-year period. PMID- 8516880 TI - Simultaneous transplantation of kidney and pancreas in diabetes patients. PMID- 8516881 TI - Duodenal segment-associated complications following combined kidney/pancreas transplantation. PMID- 8516882 TI - Combined kidney and pancreas transplantation for diabetes mellitus using modified bladder-drainage technique and employing pediatric donors. PMID- 8516883 TI - Transplantation of pancreatic islets with immunoexclusion membranes. AB - The above studies strongly emphasize that transplantation of islets using immunoisolation with hollow fiber semipermeable immunoexclusion membranes is possible. Experiments in diabetic dogs have demonstrated that both the intravascular perfusion configured device and the intraperitoneal diffusion device could be applied clinically. Future experiments must be directed toward increasing device output, extending islet viability, and utilizing islet xenografts in both perfusion and diffusion devices in large animals prior to clinical trials. PMID- 8516884 TI - Relevance of tissue typing for kidney transplantation in the Middle East. PMID- 8516885 TI - Comparison between HLA-DR serologic typing and oligotyping in kidney transplant: a single center experience. PMID- 8516886 TI - Induction therapy with antithymocyte globulin reduces the incidence of allograft rejection and improves graft survival in cadaver renal transplantation. PMID- 8516887 TI - Prospective randomized study of triple vs conventional immunosuppression in living donor kidney transplantation. PMID- 8516889 TI - Cyclosporine monotherapy versus conventional therapy in the living-related renal transplant: a one center retrospective study. PMID- 8516888 TI - Early or delayed use of cyclosporine in HLA-mismatched living-related donor renal transplants. PMID- 8516890 TI - Low-versus high-dose corticosteroid therapy in living-related kidney transplantation. PMID- 8516891 TI - Use of 15-deoxyspergualin in treatment of acute rejection in kidney transplant patients. PMID- 8516892 TI - Contribution of acute rejection to renal allograft loss from chronic rejection. PMID- 8516893 TI - Organization of organ sharing in the United States and its relevance to the Middle East. PMID- 8516894 TI - Cadaver organ donation in Saudi Arabia: a new experience. PMID- 8516895 TI - Comparative study of cadaver donor kidneys preserved in University of Wisconsin solution for less than or longer than 30 hours. PMID- 8516896 TI - Impact of donor renal function in kidney transplantation. PMID- 8516897 TI - Evaluation of potential kidney donors using digital subtraction angiography. PMID- 8516898 TI - Effect of alpha-tocopherol on the prevention of reperfusion injury caused by free oxygen radicals in the canine kidney autotransplantation model. PMID- 8516899 TI - Lidocaine metabolite formation in the liver donor as a predictive test for the safe and efficient introduction of cyclosporine in the recipient. PMID- 8516900 TI - Public awareness and attitudes toward transplantation in Cyprus. PMID- 8516901 TI - Mycobacterial infections in renal allograft recipients. PMID- 8516902 TI - Fungal mycotic aneurysms and visceral infection due to Scedosporium apiospermum in a kidney transplant patient. PMID- 8516903 TI - Leg granuloma due to Neocosmospora vasinfecta in a renal graft recipient. PMID- 8516904 TI - Benefits of bronchoscopy and bronchoalveolar lavage in the diagnosis of pneumonitis in transplant patients. PMID- 8516905 TI - Cyclosporine-associated thrombotic microangiopathy: report of two cases with good outcome and successful subsequent reuse. PMID- 8516906 TI - Haemolytic anaemia after ABO-mismatched living-donor kidney transplants. PMID- 8516907 TI - Influence of antilymphocyte globulin upon the incidence of malignancies after kidney transplantation. PMID- 8516908 TI - Ureteric complications of renal transplantation: role of percutaneous techniques. PMID- 8516909 TI - Medical and ethical aspects of living donation. PMID- 8516910 TI - Islamic position on organ donation and transplantation. PMID- 8516911 TI - Negative impact of trading in human organs on the development of transplantation in the Middle East. PMID- 8516912 TI - Allogeneic kidney cells stimulate the production of immunoregulatory cytokines in mixed kidney lymphocyte culture. PMID- 8516913 TI - Inhibitory effects of gangliosides and cyclosporine on lymphocyte activation: analysis of cytokine gene mRNA transcripts. PMID- 8516915 TI - Successful treatment of post-renal transplant erythrocytosis with enalapril. PMID- 8516914 TI - Propagation and characterization of lymphocytes infiltrating renal allografts. PMID- 8516916 TI - Differential kidney scans in preoperative evaluation of kidney donors. PMID- 8516917 TI - Twenty-four-hour blood pressure monitoring in kidney-grafted patients with multiple renal arteries. PMID- 8516919 TI - A limited access approach to native kidney nephrectomies in transplant recipients. PMID- 8516918 TI - Renal transplantation in hepatitis B surface antigen-positive patients. PMID- 8516920 TI - Ileal ureter in renal transplant recipients. PMID- 8516922 TI - Influence of warm ischemia on cyclosporine nephrotoxicity in renal isografts in rats. PMID- 8516921 TI - Favorable outcome under simple heparin therapy of recurrent anuria due to graft renal vein thrombosis and subcapsular hematoma. PMID- 8516923 TI - Cultured epithelium for skin trauma treatment: clinical and experimental studies. PMID- 8516924 TI - Organ transplantation in Tunisia. PMID- 8516925 TI - Transplantation in Turkey. PMID- 8516926 TI - Renal transplantation in Morocco: 101 transplants in 94 patients. PMID- 8516927 TI - Renal transplantation: the Lebanese experience. PMID- 8516928 TI - Transplantation in the United Arab Emirates. PMID- 8516929 TI - Omani experience with a heterogeneous group of kidney transplant recipients over a 10-year period. PMID- 8516930 TI - Renal transplantation in Cyprus. PMID- 8516931 TI - Renal transplantation and dialysis in a geriatric population in Tehran, Iran. PMID- 8516932 TI - Normal levels of coenzyme Q-10 in patients awaiting cardiac transplantation. PMID- 8516933 TI - Acute pancreatitis complicating OKT3 administration for resistant cardiac rejection. PMID- 8516934 TI - Autologous bone marrow transplantation for stage IV neuroblastoma: the role of soybean agglutinin purging. PMID- 8516935 TI - Dental aspects of cardiac transplantation. AB - This article does not cover all possible dental situations, but it is hoped that it will provide a framework on which a medical or dental consultant can develop his or her own comprehensive oral evaluation protocol for use in the screening of prospective cardiac transplant patients. It is always important for the dental consultant to remember a prospective recipient patient's primary health concern- that is, end-stage cardiac disease. The consultant should remember that many of the usual considerations for dental treatment planning must be modified and the significance of dental health placed into its proper perspective in the overall care of the cardiac transplant patient. PMID- 8516936 TI - Results of 1074 kidney transplants in Chile. PMID- 8516937 TI - Historical development of brequinar sodium as a new immunosuppressive drug for transplantation. PMID- 8516938 TI - Prevention of vascularized allograft and xenograft rejection in rodents by brequinar sodium. AB - The data that has been obtained from preclinical studies in rodents demonstrate that BQR is an effective primary immunosuppressive agent with important advantages for use in transplantation immunotherapy. The drug is highly effective when used as a single agent to prevent the rejection of a variety of vascularized allografts and xenografts. BQR is easily administered orally, the drug displays a high level of bioavailability, and drug plasma levels and immunosuppressive activity can be directly measured. The adverse side effects seen with the drug are those normally associated with antiproliferative drugs and are predictable and easily reversed by treatment withdrawal. Most importantly, perhaps, is the broad range of synergistic activity when used in combination with new immunosuppressive drugs. We believe that the combination of these attributes separate BQR from many of the new drugs now under study. Some, for example, do not exhibit synergism (CsA and FK 506), others have may have problems with inadequate oral bioavailability (MPM and rapamycin), and some exhibit the potential for substantial toxicity (15-DSG, myzorbine). The data derived from the use of BQR in combination with other immunosuppressive drugs, such as the studies described above, are important. They provide direct evidence to support the concept that the next important advances in immunosuppressive therapy will involve the use of an effective multidrug approach to preventing organ graft rejection. Combination therapies with immunosuppressive drugs that exhibit different modes of action improve graft survival, widen therapeutic windows, and reduce the risk of toxic side effects. The experimental evidence that several of these combinations are potentially useful is solid, consistent, and exciting. It is our expectation from the rodent experiments described in this symposium that the treatment of allograft (and perhaps xenograft) rejection will consist of the use of CsA (or FK 506), BQR, and a third drug such as rapamycin or mycophenolate mofetil, the choice of which will be heavily influenced by the development of either analogues of these drugs or perhaps new compounds with improved bioavailability and effective monitoring techniques. PMID- 8516939 TI - Synergistic activity of the triple combination: cyclosporine, rapamycin, and brequinar. PMID- 8516940 TI - Brequinar sodium: monitoring immunosuppressive activity. AB - There has been remarkable consistency in our laboratory for the experimental results derived from a variety of allogeneic and xenogeneic models of organ transplantation using BQR, a primary immunosuppressive agent, to prevent graft rejection. Considerable knowledge exists in a number of species with respect to the dose-response immunosuppressive efficacy, organ specificity, peripheral drug measurements, toxic side-effects, species sensitivity, and synergistic drug interactions. Despite the complexity of transferring experimental results to the clinical setting, the cumulative experience with this new immunosuppressive compound suggests that it may be highly effective when used for clinical transplantation. The identification of a predictive monitoring technique(s) would provide clinicians with a highly sensitive marker to effectively regulate BQR posttransplantation immunosuppressive therapies. Although the maintenance of a "therapeutic window" of immunosuppressive efficacy did not necessarily prevent the rejection of allografts or xenografts in the rat models tested, there was an important correlation between elevated BQR levels and the onset of recipient toxicity. Increased morbidity and mortality was noted when BQR blood levels were elevated above 16 micrograms/mL. The measurement of pyrimidine biosynthetic pathway metabolites provided a direct correlation between graft viability, global depletion of nucleotides (UTP, CTP, ATP, GTP), and suppression of PHA-mitogenic lymphocyte proliferative responses when different doses of BQR were tested. The analysis of these parameters were less informative following combination therapy with CsA. As with other immunosuppressive agents, the difficulty in relying exclusively on plasma trough drug levels as an accurate means to project graft viability may be influenced by individual differences in absorption, metabolism, and excretion of the compound. Additional parameters that may provide valuable information for the posttransplant therapeutic course include drug bioavailability, peak levels, drug clearance, or inhibition of immune response. It is anticipated that these studies will provide important baseline information for further refinement of these monitoring techniques to aid in posttransplant patient management. PMID- 8516941 TI - Brequinar sodium potentiates the effects of cyclosporine in experimental small bowel transplantation. PMID- 8516942 TI - Effect of brequinar sodium on in vivo antibody production. PMID- 8516944 TI - Use of brequinar sodium for preventing cardiac allograft rejection in primates. PMID- 8516943 TI - Mycophenolate mofetil and brequinar sodium: new immunosuppressive agents. AB - Our results demonstrate the potent immunosuppressive activity of combination MM and BQR therapy to prolong allograft survival. In addition, MM may provide a highly effective therapy for the prevention of chronic rejection. PMID- 8516945 TI - Evaluation of the use of brequinar sodium and cyclosporine combination therapy for preventing rat cardiac allograft rejection. PMID- 8516946 TI - Prolonged xenograft survival following combination therapy with brequinar sodium and cyclosporine. PMID- 8516947 TI - Individual and species differences in the in vitro sensitivity to brequinar sodium. PMID- 8516948 TI - Cardiac graft rejection in hypersensitized recipients: prevention of antibody response and graft rejection using brequinar sodium. PMID- 8516949 TI - Mycophenolic acid and brequinar, inhibitors of purine and pyrimidine synthesis, block the glycosylation of adhesion molecules. PMID- 8516950 TI - Toxicological and pharmacokinetic effects following coadministration of brequinar sodium and cyclosporine to Sprague-Dawley rats. PMID- 8516951 TI - Inhibitors of de novo purine and pyrimidine synthesis as immunosuppressive drugs. PMID- 8516952 TI - Glutamate decarboxylases and autoimmunity in insulin-dependent diabetes. PMID- 8516953 TI - Further concerns over Cheng-Prusoff analysis. AB - In his article in last month's issue of TiPS (14, 89-91), Douglas Craig discussed the application of the Cheng-Prusoff relationship to the analysis of antagonists in functional experiments. Craig described how the translation of this method from biochemistry to pharmacology can be accompanied by errors due to theoretical misunderstanding. He also emphasized the lower level of rigour associated with this means of estimating antagonist affinity constants compared with Schild analysis. In this article, Paul Leff and Iain Dougall extend Craig's arguments by describing some additional ways in which the application of the Cheng-Prusoff method to pharmacological experiments are likely to result in misinterpretation and erroneous estimates of antagonist affinity. PMID- 8516954 TI - Structure and biology of amylin. AB - Amylin is a recently discovered 37 amino acid peptide secreted into the bloodstream, along with insulin, from pancreatic beta-cells. It is about 50% identical to calcitonin gene-related peptides (CGRP alpha and CGRP beta) and structurally related to the calcitonins. Amylin can elicit the vasodilator effects of CGRP and the hypocalcaemic actions of calcitonin, while these peptides can mimic newly discovered actions of amylin on carbohydrate metabolism. The different relative potencies of these peptides suggest that they act with different selectivities at a family of receptors. Amylin is deficient in insulin dependent diabetes mellitus, while plasma levels are elevated in insulin resistant conditions such as obesity and impaired glucose tolerance. In this Viewpoint article, Tim Rink and colleagues propose that amylin is an endocrine partner to insulin and glucagon; deficiency or excess of amylin may therefore contribute to important metabolic diseases. PMID- 8516955 TI - Multiple sclerosis: some possible therapeutic opportunities. AB - Multiple sclerosis (MS) is a human disease characterized by chronic demylination in the brain caused by immunological mechanisms involving T lymphocytes and macrophages. Recently developed models of chronic relapsing forms of experimental allergic encephalomyelitis, sharing many of the clinical and pathological features of MS, and new discoveries of efficient autoregulatory mechanisms intrinsic to the immune system, have suggested new possibilities for therapeutic intervention in MS. Moreover, recent data support the concept that the immune system is exposed to a broad framework of regulation, including neuroendocrine control. In particular, interfering with secretion of the lactogenic hormone prolactin and of glucocorticoids has consistently resulted in a reduction of clinical and pathological manifestations of the disease. In this review, Frank Berkenbosch and colleagues highlight several of the possible therapeutic opportunities for the treatment of MS. PMID- 8516956 TI - Measurement of mean velocity during pulsatile flow using time-averaged maximum frequency of Doppler ultrasound waveforms. AB - It has been suggested that mean velocity of flow could be estimated by the time averaged maximum frequency over an integral number of cardiac cycles (Gill 1985). The present study verified this theory experimentally with a computer-controlled flow phantom. The effects of some parameters on the relationship between mean velocity and time-averaged maximum frequency were also studied. Parameters investigated included beam-vessel angle, diameter of tubing, pulsatility, flow rate and stenosis. The velocities measured by the Doppler system were compared with the actual velocities. A simple theoretical model was also developed to compare with the experimental results. The results showed that, in a long straight tube, the mean velocity can be estimated to within about 5% from the time-averaged maximum Doppler shift at various flow rates and pulsatilities. The error due to geometrical spectral broadening, especially for large beam-vessel angles, can be estimated to within 3% and therefore corrected. PMID- 8516957 TI - Transverse Doppler spectral analysis for a correct interpretation of flow sonograms. AB - The classic Doppler equation predicts that scatterers moving transversely to the ultrasound beam yield a zero frequency shift in the received echoes. An original theoretical approach, which has been developed in the last few years, has demonstrated that any focused beam leads to the generation of a Doppler spectrum with a nonzero bandwidth even for a transverse flow orientation. Based on this new theory, it is shown here that "transverse" Doppler spectral analysis can also be usefully applied in vivo. Experimental results obtained by observing normal and diseased carotid arteries at 90 degrees show that the information obtained with this approach is complementary to that provided by the mean frequency alone, which is given by the classic Doppler equation. PMID- 8516958 TI - Applications of lipid-coated microbubble ultrasonic contrast to tumor therapy. AB - Lipid-coated microbubbles (LCM) make an excellent diagnostic ultrasonic contrast agent in experimental tumor systems. LCM have been shown to aggregate in brain tumors and subcutaneous tumors after intravenous administration, and to provide persistent image enhancement for many minutes. In this work, experimental subcutaneous Walker Carcinosarcoma is insonated after the bubbles are given intravenously. Selective necrosis, lymphocyte proliferation and hemorrhage within the tumor can be demonstrated. Preliminary data are given to demonstrate this phenomenon. The mechanism of the effect is discussed in the context of both heating and cavitation. PMID- 8516959 TI - Morphological effects of pulsed ultrasound in the lung. AB - We have previously described the induction of subcapsular hemorrhage in the murine lung by extracorporeal shock wave lithotripsy at exposures of 2 MPa (Hartman et al. 1990) and pulsed ultrasound (Child et al. 1990). Since extravasation of erythrocytes and alveolar flooding are prominent, we proposed to determine whether or not the injury was progressive, by continuing to develop following termination of exposure, and by localizing where the injury was developing. Mice were exposed to 10 microsecond impulses at 1.6 MPa for 3 min and sacrificed either immediately or 5 min following exposure. When observed with both light and transmission electron microscopy, there was no gradation in lung injury, with a sharp demarcation of the hemorrhagic area. Moreover, both type I pneumocytes and capillary endothelial cells were injured, causing direct continuities between vessel lumina and alveolar spaces. In the absence of extravasation, the tissue appeared normal. There was no evidence that injury increased in severity during the first 5 min after exposure. PMID- 8516960 TI - Biological effects of laser-induced shock waves: structural and functional cell damage in vitro. AB - A new experimental design has been used to study the biological effects of laser induced shock waves which minimizes or eliminates interference from ancillary effects such as bubble formation, ultraviolet (UV) radiation, or formation of radicals. The effects of these shock waves on human lymphocytes and red blood cells have been investigated. Three assays were used to determine cell injury: electron microscopy, ethidium bromide/fluorescein diacetate (EB/FDA) staining and incorporation of tritiated thymidine. The degree of cell damage was related to the pressure and the number of pulses. Cell damage was quantified and correlated using the three assays. Measurements of gross structural alterations as determined by transmission electron microscopy were less sensitive than assays of structural damage (e.g., EB/FDA assay) which were less sensitive than functional assays (e.g., incorporation of tritiated thymidine). PMID- 8516961 TI - Lysis of erythrocytes by exposure to CW ultrasound. AB - The threshold for lysis of erythrocytes suspended at concentrations of 0.5-1% in saline or plasma in rotating cylindrical exposure vessels is approximately spatial peak intensities of 2 W/cm2 at 1 MHz continuous wave (CW). Results of a series of experiments in which cell concentration, viscosity and gas composition of the suspending medium and rotation speed of the exposure vessel were varied combined with observations of sonoluminescence are all consistent with a hypothesis that cells are lysed by inertial (transient) acoustic cavitation. For the proposed mechanism to operate in cell suspensions, it is necessary that bubbles be brought into contact with the cells. Rotation of the chamber recycles bubbles that are driven by radiation forces to the far wall of the chamber in a matter of milliseconds. The physical and chemical properties of the wall of the chamber appear to be important as stabilizing sites for nuclei that serve as seeds for cavitation events. PMID- 8516962 TI - Acoustic streaming generated by a focused Gaussian beam and finite amplitude tonebursts. AB - Theoretical models for calculating the on-axis acoustic streaming velocity generated by a continuous-wave (CW) and pulsed finite amplitude ultrasonic beams have been developed. Using these models, the on-axis streaming velocity is calculated for unfocused linear plane wave ultrasonic beams, focused linear Gaussian beams, and unfocused ultrasonic tonebursts of finite amplitude. The numerical results show that the on-axis streaming velocity is significantly enhanced by the nonlinear harmonic generation of finite-amplitude ultrasonic tonebursts. PMID- 8516963 TI - Three-dimensional colour Doppler imaging. AB - We have developed a system to acquire in vivo three-dimensional (3D) colour velocity images of peripheral vasculature. A clinical ultrasound system was modified by mounting the transducer on a motor-driven translation stage, allowing planar ultrasound images to be acquired along a 37 mm long stroke. A 3D velocity image is acquired by digitizing, in synchrony with the cardiac cycle, successive video images as the transducer is moved over the skin surface. 3D images require about 1 min to acquire and 10 min to reconstruct before being viewed interactively. Image acquisition at several points in the cardiac cycle permits a cine-type reconstructed image. Geometrical, temporal and velocity accuracy of the acquisition and reconstruction have been quantified and found not to degrade the image. PMID- 8516964 TI - "Admit medical". PMID- 8516965 TI - Traumatic carotico-cavernous fistula presenting as delayed epilepsy. PMID- 8516966 TI - Absence of the odontoid process with atlanto-axial subluxation; anaesthetic aspects. PMID- 8516967 TI - Birth following replacement of frozen-thawed embryos in an in vitro fertilization programme. PMID- 8516968 TI - Myeloma--results of treatment 1986-1990. AB - Sixty-nine patients with multiple myeloma diagnosed during a five year period at the Belfast City Hospital were followed until death or for a minimum of one year in a retrospective study of survival. Although the patients were unselected, survival data was found to be similar to results from trials in which patient selection had occurred. Overall median survival was thirty-two months. Median survival fell with advancing disease and was 47, 27 and 18 months for Durie Salmon stages I, II and III respectively. Those patients presenting with a platelet count of < 100 x 10(9)/1 had a median survival of eight months in contrast to those with a platelet count > 100 x 10(9)/1 whose median survival was 36 months. Patients presenting in renal failure had a shorter median survival of 28 months compared to 46 months for those with normal renal function. PMID- 8516969 TI - Five cases of hepatitis A jaundice: diagnostic problems during an epidemic. PMID- 8516970 TI - Idiopathic pulmonary haemosiderosis and smoking. PMID- 8516971 TI - Day-case arteriography. AB - Outpatient femoral arteriography has been carried out in 100 consecutive patients presenting with evidence of peripheral vascular disease. Patients have been observed for seven hours in an observation ward bed. No bleeding or other complications have been encountered. The cost-saving to the hospital is approximately 60.00 pounds per case. More importantly, the service to patients has been improved, with less chance of last minute cancellation due to unavailability of a surgical bed. PMID- 8516972 TI - Anaesthetic monitoring: clinical practice in anaesthetic rooms and theatres. AB - Twenty anaesthetic rooms and operating theatres in Northern Ireland were visited in both 1990 and 1992. Data was collected on the availability and use of anaesthetic monitoring. In the anaesthetic rooms there were few pulse oximeters. In the theatres more monitors were available and in use. Some change in practice had occurred between 1990 and 1992, notably an increase in the monitoring of ventilation, and in the availability of printer facilities for documentation of anaesthetic records. PMID- 8516973 TI - Perinatal outcome and antenatal care in a black South African population. AB - The relationship between perinatal outcome and antenatal care was investigated at King Edward VIII Hospital, Durban, by a case control retrospective study of pregnancy records in 165 perinatal deaths and 156 infants surviving the perinatal period. 82% of the mothers of live infants had booked for antenatal care compared with only 60% of those who experienced a perinatal death. Hospital booking was associated with a higher infant birthweight. For those who booked earlier there was no reduction in total perinatal mortality or the stillbirth:neonatal death ratio, and many of the mothers of highest risk failed to book. This suggests that the better perinatal outcome in booked mothers may have been secondary to the type of mother who chose to book, rather than the actual antenatal care. To help reduce perinatal mortality, methods must be employed which reach those mothers who are most likely to fail to book. PMID- 8516974 TI - Differences between "geriatric" and "medical" patients aged 75 and over. AB - We analysed the characteristics of patients aged 75 and over admitted to the geriatric and general medical wards over a three month period in a teaching hospital. Patients admitted to the geriatric wards were slightly older, were more often female, more likely to be admitted during the day and during a week day, more likely to have been seen by their own general practitioner, had more chronic and multiple illness with non-specific presentations, and stayed longer in hospital. Referring doctors seem to discriminate between patients needing geriatric care and those more suitable for general medical care, but there is an overlap in the characteristics of the two groups. PMID- 8516975 TI - Pancreatic polypeptide and exocrine pancreatic function in the elderly. AB - The relationship between exocrine pancreatic function and plasma pancreatic polypeptide levels was studied in 14 normal elderly subjects and in ten elderly patients with exocrine pancreatic insufficiency determined by the para-amino benzoic acid test. There was a decrease in the total pancreatic polypeptide response after a standard mixed meal in the group with pancreatic insufficiency (t = 2.753, p = 0.01). An increase above basal of less than 100% in plasma pancreatic polypeptide levels 30 min after a standard mixed meal is strongly associated with exocrine pancreatic insufficiency (Fisher's exact test, p = 0.005). PMID- 8516976 TI - Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing. AB - Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital. PMID- 8516977 TI - Alcohol-related attendances at an accident and emergency department. AB - Using a self-administered alcohol-related questionnaire and the clinical records a survey was made of the prevalence and severity of alcohol-related problems in the accident and emergency department at the Belfast City Hospital. Of 10,410 consecutive attendances during three months, 6,625 completed a questionnaire: 4,349 admitted they took alcohol at some time, 906 men exceeded 21 units weekly, and 490 women exceeded 14 units weekly. The majority of those who drank were under the age of 35 years. Only 182 considered that they might have an alcohol related problem. Possible health promotion initiatives for these at-risk patients are considered which might be used specifically in an accident and emergency department. PMID- 8516978 TI - Hysteroscopic metroplasty. AB - Four patients with reproductive failure associated with uterine septa had transvaginal hysteroscopic metroplasty performed. Two successful pregnancies have occurred and a third patient is now in the second trimester of pregnancy. This method of treatment should replace the traditional open method of surgical repair of these malformations. PMID- 8516979 TI - The health of the public--from Cos to Maastricht. PMID- 8516980 TI - "An image for tomorrow." An image for change--annual oration at the opening of the 1992-93 teaching session at the Royal Victoria Hospital. PMID- 8516981 TI - The centenary of Ivy Cottage, Belfast City Hospital. PMID- 8516982 TI - Anaplastic carcinoma of the paranasal sinuses presenting as a nasal polyp. PMID- 8516983 TI - Modification of Mitrofanoff principle for continent urinary diversion. AB - In 1980, Mitrofanoff described a method of achieving continent urinary diversion by surgically closing the bladder neck and creating a continent catheterizable stoma from the appendix, which had been implanted in a non-refluxing manner into the bladder, or from a non-refluxing distal ureter. We describe a modification of the Mitrofanoff procedure for continent urinary diversion in 7 children in whom a standard Mitrofanoff procedure was not possible due to either body habitus or appendiceal anatomy. All 7 patients are continent both day and night. Four have required stomal revisions. Renal function has remained stable or improved in all patients. Although the revision rate was high, this modification of the Mitrofanoff principle has provided good long-term results in these patients and may be useful when patient's anatomy does not allow the creation of a standard appendicovesicostomy. PMID- 8516984 TI - Bellevue pouch: ileocolonic continent urinary reservoir. AB - The technique for the Bellevue Pouch, another continent intestinal reservoir, is described. A large-capacity low-pressure reservoir is created from detubularized ascending colon, cecum, and terminal ileum. Continence is achieved by means of an intussuscepted segment of ileum and a modulating colonic pressure cuff wrapped around it. The operation has been performed on 19 patients, all of whom achieved satisfactory continence. Two patients were converted to free drainage systems at a later date. Average follow-up was twenty-five months. PMID- 8516985 TI - Stanford pouch ileal neobladder: clinical, radiologic, and urodynamic follow-up. AB - The Stanford pouch is an orthotopic neobladder which consists of a reservoir made from 30 cm of detubularized ileum and an antireflux segment based on a series of intestinal pleats. The clinical, radiologic, and urodynamic follow-up of 40 patients who have undergone the operation and have been followed for at least six months is presented. Renal function, based on serum creatinine levels, has remained stable. Voiding cystourethrograms obtained in 34 patients revealed that 38 percent of patients had no reflux. Of the 62 percent of patients with reflux, 49 percent had grades I-II/V reflux and 51 percent had grades III-IV/V reflux. Imaging of the upper urinary tracts in 32 patients revealed mild hydronephrosis in 3/64 (4.7%) of renal units. Daytime continence was attained in 95 percent of patients, and nighttime continence in 59 percent of patients. Urodynamic studies in 30 patients revealed an average capacity of 695 cc, phasic contractions whose mean pressure was less than 40 cm water, and a low basal neobladder pressure of 21.9 cm water at capacity. Twenty-four-hour voiding diaries in 24 patients revealed an average voided volume of 267 cc, a mean maximum voided volume of 445 cc, and a mean frequency of urination of one hundred eighty-two minutes. Based on these results, the Stanford pouch is a viable form of continent diversion to the urethra. PMID- 8516986 TI - New continent ileocolonic urinary reservoir: Charleston pouch with minimally altered in situ appendix stoma. AB - A new continent urinary reservoir that utilizes minimally altered in situ appendix stoma is described. The reservoir was constructed from segments of terminal ileum and ascending colon which were detubularized and reorientated to provide maximum reduction in filling pressures. The in situ appendix was utilized to provide a continent catheterizable stoma. Appendicular leak pressures were measured intraoperatively to determine the need, if any, for augmentation. Minimal reinforcement of the appendiculo-colonic junction with two or three sutures was performed in most patients. Preliminary experience with 16 patients who had the Charleston pouch with an appendicular stoma as described herein is reviewed. PMID- 8516987 TI - Intravesical oxybutynin chloride: experience with 42 patients. AB - To evaluate the efficacy of intravesical oxybutynin chloride, 42 patients who were incontinent secondary to uninhibited detrusor contractions and had failed oral anticholinergic therapy were begun on intravesical oxybutynin chloride. Indications for intravesical therapy were detrusor hyperreflexia (N = 20), detrusor instability (N = 19), and bowel/bladder overactivity after augmentation cystoplasty (N = 3). A 5-mg tablet dissolved in 30 cc of sterile water was instilled into the bladder two to three times daily via clean self intermittent catheterization. With a mean follow-up of 18.4 months, no patient reported side effects as a result of the intravesical therapy. Nine patients (21%) dropped out of the study due to inability to tolerate the catheterization or difficulty retaining the solution in the bladder. Eighteen of the 33 patients (55%) who followed the protocol experienced elimination or significant improvement of their incontinence. The results of the current study confirm the safety and usefulness of intravesical oxybutynin in treating uninhibited detrusor contractions in a difficult patient population. PMID- 8516988 TI - Bladder rupture associated with pelvic fracture due to blunt trauma. AB - A total of 103 patients with pelvic fracture due to blunt trauma were evaluated by cystography and 10 cases of bladder rupture were identified. Risk factors associated with the likelihood of bladder rupture included gross hematuria, the number of fractured pubic rami, tachycardia, hypotension, and declining hematocrit. We conclude that since 90 percent of the patients do not have bladder rupture when a pelvic fracture is encountered, cystography may be safely reserved for those patients with pelvic fracture who are considered to be at high risk for such an injury. PMID- 8516989 TI - Survival characteristics of metastatic renal cell carcinoma patients treated with lymphokine-activated killer cells plus interleukin-2. AB - The immunologic manipulation of patients with metastatic renal cell carcinoma using lymphokine-activated killer (LAK) cells in conjunction with systemic interleukin-2 (IL-2) has been examined under conditions in which the life threatening toxicities associated with IL-2 treatment have been virtually eliminated. We have examined tumor regression in vivo as well as the survival characteristics of 12 patients with metastatic renal cell carcinoma following immunotherapy. Five of 12 (42%) patients experienced tumor regression exceeding 50 percent following treatment. To determine if immunotherapy had influenced the length of survival, all patients were followed until the time of death. Previous studies have characterized the length of survival of metastatic renal cell cancer patients according to a combination of risk factors unique for each patient. In this model, patients were categorized into risk groups based on the number of risk factors. Survival was found to be dependent on risk factors such as performance status, time from initial diagnosis, number of metastatic sites, recent weight loss, and prior cytotoxic chemotherapy. On completion of the LAK cell immunotherapy protocol, patients were categorized as nonresponders or responders. In addition, they were assigned to risk groups based on their unique profile of risk factors at the time of entry into the protocol. Using this model, we found the median survival of nonresponders (23 months) to be no different from responders (24 months), p > 0.05. This was directly attributable to differences in risk factors which characterized members in these two response groups. However, the observed median survival of nonresponders following therapy was 1.9 fold longer than their projected survival based on the risk factors. Furthermore, the observed median survival of responders was 3.4-fold longer than projected from their risk factors. These results suggest that regardless of response status to therapy, cellular immunotherapy may play a role in mediating a significant palliative effect on the metabolic characteristics of these patients leading to extended survival. PMID- 8516990 TI - Transrectal hyperthermia as palliative treatment for advanced adenocarcinoma of prostate and studies of cell-mediated immunity. AB - During a fifteen-month period, 15 patients with progressive adenocarcinoma of the prostate (CaP) were treated with transrectal microwave hyperthermia (TRHT). There were 5 Stage T4 and 11 Stage T3 patients including 6 patients with skeletal metastases. Nine of the patients had severe and 6 had moderately severe signs and symptoms of CaP. TRHT was given six times at 2,450 MHz with temperature controlled at 43.5 degrees for thirty minutes. Cell-mediated immunity tests were performed before TRHT and at two, four, and six months post-therapy. The results of these tests were compared with those of 15 patients with benign prostatic hyperplasia (BPH) treated with the same TRHT and with 30 untreated normal volunteers. TRHT was well tolerated with mild acute toxicity noted in 3 patients (20%). Of the 15 patients treated, 2 (13%) showed scintigraphic evidence of regression of bone metastases. Five patients survived more than five years since treatment, and in 3 patients there was no evidence of CaP. A decrease of marked or moderate degree in signs and symptoms of CaP was noted in 8 patients (53%). The results of cell-mediated immunity tests were of interest. The 15 CaP patients prior to TRHT had lower OKT4/OKT8 ratio, lower PHA transformation index, and lower Con-A induced T-cell suppressor activity as compared with the 15 BPH patients and 30 healthy volunteers, who had normal immune parameters (p < 0.01). Following TRHT there was a significant increase in the monitored immune parameters noted in the 15 CaP patients (p < 0.01). This immune stimulation peaked at two months and gradually decreased to near pretreatment levels at six months. In the 15 BPH patients post-TRHT changes in immune tests were less apparent. The results of this small study, if confirmed, could be of clinical importance in patients with advanced prostate cancer. PMID- 8516991 TI - Unrecognized congenital posterior urethral minivalves in men. AB - Removal of small congenital posterior urethral valves, unrecognized in prior urologic investigations of 10 men, relieved "prostatic" symptoms in 9. In follow ups (5-20 years, average 12.5 years), 3 have experienced a recurrence attributed to bladder neck obstruction in 2 and to unknown causes in 1. Bladder neck incision carried out in 2, cured 1. The other was lost to follow-up. PMID- 8516992 TI - Cutaneous vesicostomy in the young child: indications and results. AB - With newer methods of managing lower urinary tract pathology in the young child, the role of cutaneous vesicostomy may be changing. This prompted a review of 50 consecutive patients treated with initial vesicostomy at our center over ten-year period. These children underwent vesicostomy diversion at a median age of 5.8 months and, of the 34 vesicostomies which have been subsequently closed, for a median duration of twenty-five months. Our indications agree with series reported previously and include patients with meningomyelocele, posterior urethral valves, or other forms of congenital or acquired lower urinary tract anomaly or dysfunction, along with complicating factors such as vesicoureteral reflux, recurrent infections, and/or renal deterioration. However, we also have identified a major group--those with primary gross vesicoureteral reflux--not previously included in detail. Follow-up averaged thirty-eight months. Improvement or stabilization of upper urinary tracts was achieved in over 90 percent of cases, and this trend continued after vesicostomy closure. As well, cutaneous vesicostomy allowed ureteral dilation to normalize, decreasing the degree of reflux and need for subsequent ureteral tapering and reimplantation at closure. Finally, though our stomal revision rate of 20 percent is high, modified techniques are being pursued. PMID- 8516993 TI - Penile agenesis associated with urethral and bilateral renal agenesis. AB - Penile agenesis is a rare anomaly, with an estimated incidence of 1 in 30 million. Most cases are compatible with life but require early surgical intervention. This case is unusual in that there was an associated agenesis of the kidneys and urethra leading to fatal oligohydramnios sequence with pulmonary hypoplasia. PMID- 8516994 TI - Preservation of bladder neck fibers in radical prostatectomy. PMID- 8516995 TI - Squamous cell carcinoma arising from suprapubic cystotomy site without bladder involvement. AB - We report on an eighty-year-old Haitian man with a suprapubic mass of seven months duration after five years of urinary diversion for urethral stricture. Histologically the mass was a squamous cell carcinoma confined to the suprapubic tract without bladder involvement. We believe this is the first such case reported in the literature, and it stresses the need for close monitoring of patients with any type of long-term indwelling catheter. PMID- 8516996 TI - Ectopic ureter presenting in midline urethral diverticulum. AB - A rare case of an ectopic ureter terminating in a urethral diverticulum is presented. While numerous cases of extravesical ectopic ureters draining directly into the urethra or uterovaginal canal have been reported, the termination of a ureter as a diverticular sac is extremely unusual. Moreover, only rarely has a urethral diverticulum been documented to arise congenitally due to any cause. The history and management of this new case are detailed, and the general subjects of ectopic ureter and urethral diverticulum are discussed with particular reference to etiology and continence. PMID- 8516997 TI - Nonoperative management of bilateral shattered kidneys from blunt trauma. AB - Bilateral shattered kidneys secondary to blunt abdominal trauma has not, to our knowledge, been reported. In the case reported herein, severe pulmonary, myocardial, and orthopedic injuries necessitated nonoperative management of this peculiar injury. The patient recovered without sequelae related to the renal injury. PMID- 8516998 TI - Metastatic renal tumor presenting as ovarian clear cell carcinoma. AB - Patients with clear cell adenocarcinoma of the kidney often present with metastatic disease, in some cases involving organs in which primary clear cell tumors occur. Under these circumstances, diagnosis of the renal primary tumor may be delayed. Herein we present a case of renal cell carcinoma metastatic to the ovaries initially treated as primary ovarian disease, until the appearance of other metastases prompted the discovery of its true origin. A high index of suspicion and the histologic characteristics of these tumors may allow earlier diagnosis and treatment of a renal primary tumor. PMID- 8516999 TI - CO2 laser welding versus conventional microsuture repair in patch-graft urethroplasty. AB - This study evaluates the repair of urethral tissue using microsurgery and a combination of laser welding techniques. Using the rat as a model, a patch-graft urethroplasty was performed with either conventional microsuture repair, laser assisted microsuture repair, or laser-assisted microsuture with protein solder. Repairs were assessed at various time periods (days 0, 1, 7, and 21). Analysis of success rate, bursting strength, histology, and operative time were completed. The laser with protein solder had the highest success rate at each time period and demonstrated advanced healing with the least amount of inflammation. Operative time was decreased by 30 percent using the laser. In conclusion, the laser solder repair was significantly better than either laser alone or conventional microsutures. PMID- 8517000 TI - Value of transrectal prostate ultrasonography pre-transurethral prostatectomy in screening for occult prostate carcinoma. AB - A total of 311 patients who underwent consecutive transurethral resection of prostate (TURP) for obstructive voiding symptoms were reviewed. All patients had benign prostate glands by digital rectal examination. Results of preoperative ultrasound screening of the prostate in 65 of 311 patients showed 41 with nonmalignant prostate, but pathologic examination showed cancer in 11 and benign hyperplasia in 30. Of seven ultrasounds interpreted as suspicious for cancer, pathologic examination revealed benign hyperplasia in all seven. Of 17 patients with ultrasound interpretations consistent with prostate cancer, 14 had transrectal ultrasound-guided prostate biopsies prior to TURP. Biopsy specimens revealed benign hyperplasia without carcinoma in all 14 patients. Two of 17 patients refused biopsies, and 1 underwent TURP without biopsy for urinary retention and did have cancer. Sensitivity of prostate ultrasound in evaluation of occult prostate carcinoma in this group of patients was 8.3 percent and specificity was 56.6 percent. Our results indicate that transrectal prostate ultrasound performed on men with obstructive voiding symptoms and benign glands as evidenced by digital rectal palpation has little value in predicting the presence or absence of occult prostate cancer. PMID- 8517001 TI - Analysis of solid renal dysplasia by flow cytometry: malignant potential? AB - Renal nodular blastema/nephroblastomatosis is a recognized precursor of Wilms tumor. It also has been shown that nodular renal blastemata are seen in association with dysplastic renal parenchyma secondary to obstructive uropathy (i.e., ureteroceles or ectopic ureters). In an attempt to improve our understanding of the critical relationship between renal dysplasia and neoplasia, we performed flow cytometric evaluation on 16 paraffin-embedded specimens of dysplastic kidneys removed during the period 1984-1989. All nephrectomy specimens were associated with obstruction, either duplex collecting systems (10), ectopic ureters (2) or posterior urethral valves (2), or vesicoureteral reflux (2). One specimen was found to contain nodular renal blastema. No evidence of malignancy was found in any specimen. A specimen of normal kidney and two of Wilms tumor (favorable histology) were studied for comparison. Nuclear deoxyribonucleic acid (DNA) ploidy studies were performed on single dissociated nuclei after deparaffinization and staining with propidium iodide. All dysplastic specimens, including the specimen with nodular renal blastema, demonstrated a diploid pattern of DNA as did the specimens of normal renal tissue. The Wilms tumor specimens demonstrated a diploid and a tetraploid pattern. In view of the fact that Wilms tumor may demonstrate diploid DNA patterns on flow cytometry, the findings of diploid patterns on all specimens of solid dysplasia militate against but do not eliminate the possibility of malignant degeneration. PMID- 8517002 TI - Secondary carcinoma of kidney from parotid gland tumor. AB - Secondary tumors of the kidney are rarely diagnosed during life. However they should be suspected in a patient with a primary malignancy of nonrenal origin and a renal mass. A case of parotid cancer metastatic to the kidney is presented. This case is unique because of its rarity, clinical presentation, and pathologic findings. PMID- 8517003 TI - Radiotherapy versus surgery for stage C prostate cancer. PMID- 8517004 TI - Serological reactions to Brucella species in British pigs. AB - Until and including 1987 diagnostically significant serological titres to swine brucellosis had occurred in the serum agglutination test (SAT) or the complement fixation test (CFT), ie, > or = 100 iu or > or = 20 icftu, respectively, almost every year since reliable records began, but usually only about 0.05 per cent in the SAT and 0.005 per cent in the CFT. Brucella suis was never isolated by cultural examination. In 1988 the level of CFT reactions > or = 20 icftu rose to 0.42 per cent (1.04 per cent in the last quarter of the year) but the SAT reactions remained relatively unchanged. In 1989 the levels of both CFT and SAT reactions increased further with CFT reactions again predominating. Analyses of the serological reaction patterns in individual herds suggested that infection with brucella or some other organism capable of causing serological cross reactions had become widespread in Great Britain, although signs of disease typical of swine brucellosis had not been observed. Some herds had reactions which persisted for many months whereas others showed them for only a short time. In early 1990 Yersinia enterocolitica serogroup O:9 was isolated from some pigs purchased from one of the reactor herds and this organism is probably responsible for the increased numbers of seroreactions. It had not previously been found in pigs in Great Britain. PMID- 8517005 TI - Efficacy of abamectin against ectoparasites of cattle. AB - Four trials, using 48 European breed cattle, were conducted to evaluate the efficacy of abamectin against the louse species Linognathus vituli, Haematopinus eurysternus and Damalinia bovis and against the mange mites Sarcoptes scabiei var bovis and Psoroptes ovis. Animals were allocated by restricted randomisation based on parasite counts to treatment with abamectin at a dose of 200 micrograms/kg given subcutaneously or to an untreated control group. Ectoparasites were counted before treatment and at weekly intervals thereafter for eight weeks. L. vituli, H eurysternus and S scabiei var bovis were eliminated (P < 0.05) by day 7 after abamectin treatment. An efficacy of more than 99 per cent was recorded against P ovis mange mites. The biting louse D bovis was not controlled. Abamectin treatment increased the weight gain of cattle infested with ectoparasites. PMID- 8517007 TI - Necrotic dermatitis and otitis media associated with Pseudomonas aeruginosa in sheep following dipping. PMID- 8517006 TI - Clinical signs and radiographic diagnosis of a portosystemic shunt in a foal. AB - A three-month-old native pony foal had a history of recurrent episodes of bizarre neurological behaviour. The results of clinical examinations were non-specific but clinicopathological investigations indicated hepatic encephalopathy. A percutaneous, needle liver biopsy revealed histopathological changes consistent with a portosystemic shunt, which was later identified by operative mesenteric portovenography, and confirmed at post mortem. PMID- 8517008 TI - Swine influenza outbreaks in England due to a new H1N1 virus. PMID- 8517010 TI - Law enforcement: carrot or stick? PMID- 8517009 TI - Improved reproductive performance in cattle dosed with trace element/vitamin boluses. PMID- 8517011 TI - Acute respiratory distress syndrome in yearling cattle. PMID- 8517012 TI - Database for bovine abnormalities. PMID- 8517013 TI - Low level of genetic drift in foreign sequences replicating in an RNA virus in plants. AB - The accumulation of mutations was measured in foreign sequences constituting a portion of a hybrid virus derived from the 6.4-kb (+) RNA virus, tobacco mosaic tobamovirus (TMV). Neither of the two foreign sequences tested (dihydrofolate reductase and neomycin phosphotransferase II) are functionally required by the virus, so they should be free of selective pressures and should be a true measure of viral sequence drift in whole plants. Four hybrid virus populations, two of each foreign sequence, were taken through 9-10 passages in whole plants of Nicotiana benthamiana. Sequences were sampled from these populations by conversion to cDNA, amplification by the polymerase chain reaction, and sequencing resulting bacterial clones. The background mutation rate contributed by the enzymes of this assay system allowed viral mutation rates greater than 10( 4) mutations per base per passage to be measured. Surprisingly, all native and foreign genes accumulated mutations at a very low rate, lower than could be detected by the assay procedure. This low mutation accumulation rate of < or = 10(-4) mutations per base per passage may be due to replicase fidelity or populational "bottlenecking." Sequence drift should not be a practical limitation to most uses of TMV as a vector, although deletion phenomena observed in this study may present difficulties. PMID- 8517014 TI - Identification and characterization of a family of 11-kDa proteins encoded by the human parvovirus B19. AB - The human pathogenic parvovirus B19 directs the synthesis of two size classes of small abundant RNAs. It is shown that the smallest RNAs, of 500 and 600 nt, are translated into at least two 11-kDa proteins in B19-infected human leukemic bone marrow cells. A COS-7 cell expression system was used to demonstrate that the different forms of the protein result from translational initiation at multiple AUG codons in the same 94 aa ORF. The 11-kDa proteins were localized to the cytoplasm of transfected COS-7 cells using indirect immunofluorescence. However, their localization was at least partially nuclear in B19-infected cells. In COS-7 cells the expression of the major B19 structural and nonstructural proteins was not affected in the absence of the expression of the 11-kDa proteins. PMID- 8517015 TI - The Fc portion of antibody to yellow fever virus NS1 is a determinant of protection against YF encephalitis in mice. AB - The mechanism by which antibodies to the flavivirus nonvirion protein NS1 protect mice against encephalitis is unknown but their binding to cell surface NS1 raises the possibility of involvement of an Fc piece-directed immune function. To investigate this, we prepared the F(ab')2 moiety of a protective IgG2a monoclonal antibody (Mab) against yellow fever virus (YF) NS1 and isolated IgG2a- and IgG2b secreting isotype switch variants from a hybridoma that secretes a nonprotective IgG1 anti-YF NS1 Mab. Each Mab, complexed to NS1, bound to macrophage Fc receptor (FcR) but only the IgG2a and IgG2b Mabs sensitized YF-infected cells to complement-mediated cytolysis. Passively transferred IgG2a Mabs, but not F(ab')2, IgG1, or IgG2b Mabs, interfered with replication of YF in mouse brain. IgG2a Mabs protected mice against YF encephalitis but passive transfer of a mixture of variant IgG2a and parent IgG1 Mabs, or of unrelated IgG2a and IgG1 Mabs directed at the same NS1 epitope, resulted in markedly reduced protection, findings that may bear on flavivirus vaccine design. IgG2a Mab interfered with CNS YF replication in, and protected, C3-depleted mice, but not mice treated with high dose cyclophosphamide to eliminate antibody-dependent killer cell activity. Taken together, these results indicate that epitope specificity alone may be inadequate to account for protection by anti-NS1 antibody and are consistent with involvement of an FcR-dependent protective mechanism that is governed by antibody isotype. PMID- 8517016 TI - Identification of an Amsacta spheroidin-like protein within the occlusion bodies of Choristoneura entomopoxviruses. AB - Like baculoviruses, a characteristic feature of entomopoxviruses is the amalgamation of virions within environmentally stable occlusion bodies. It is this occluded form of the virus that is primarily responsible for dissemination to other insects. While the major protein (polyhedrin) of baculovirus occlusions is quite similar between viruses, it has been reported that the major occlusion body protein (spheroidin) of two group B entomopoxviruses, Amsacta moorei (AmEPV) and Choristoneura biennis (CbEPV) is quite different both in terms of amino acid sequence and coding capacity of the corresponding spheroidin genes (115 and 47 kDa for AmEPV and CbEPV, respectively). We report the discovery of a AmEPV spheroidin gene homolog in both CbEPV and a second Choristoneura virus, Choristoneura fumiferana (CfEPV). Antibodies directed against the AmEPV 115-kDa spheroidin reacted with the major protein of approximately 115 kDa found within the occlusion body preparation from both Choristoneura viruses. Direct protein microsequencing of small portions of the 115-kDa protein from CbEPV has resulted in peptide sequences identical to those of corresponding regions of the AmEPV spheroidin gene. We suggest that it is this Choristoneura gene which encodes spheroidin. All attempts, however, to find a homolog of the previously reported CbEPV spheroidin gene within AmEPV have been unsuccessful. We also show this newly identified Choristoneura homolog of the AmEPV spheroidin gene as well as the AmEPV spheroidin gene itself are both located at the 3' end of an NPH I gene and are highly homologous in all three viruses, indicating that this region of the genome in the three viruses is co-linear. These results and others suggest that while the insect viruses lack the traditional central core of conserved genes observed for the vertebrate poxviruses, the insect poxviruses may have also evolved an alternative central core of conserved genes, unique to the invertebrate poxviruses. PMID- 8517017 TI - In planta deletion of DNA inserts from the large intergenic region of cauliflower mosaic virus DNA. AB - RNA splicing and copy-choice recombination lead to deletions in the DNA of cauliflower mosaic virus (CaMV). To assess the relative importance of these mechanisms of nucleotide sequence change, free of constraints imposed by the "relay race" mode of translation of CaMV RNA, we examined the stability of inserts in the large intergenic region. The insertions had, in various combinations, splicing signals and directly repeated sequences that could facilitate deletion. Most modified DNAs were infectious. Viral DNA recovered from infected plants was analyzed by restriction and, in some cases, cloned for nucleotide sequencing to determine deletion endpoints. Deletions from a DNA containing introduced splicing signals occurred primarily at direct repeats, although deletion apparently by splicing was also detected. Both types of deletion were also observed with insertions containing a 5' splice donor but no known functional 3' splice acceptor. One DNA, whose insertion lacked splicing signals and short repeated sequences, was stable in one of two plants infected. Total insert deletions were bounded by repeats or pseudorepeats, while partial insert deletions apparently occurred by splicing. The results suggest that the two mechanisms for deletion of nucleotides are equally important in the evolution of caulimoviral nucleotide sequences. PMID- 8517018 TI - Cloning and sequence analysis of a p40 structural protein gene of Helicoverpa zea nuclear polyhedrosis virus. AB - A gene encoding an occluded virion structural protein was isolated from an expression library constructed from the Helicoverpa zea S-type nuclear polyhedrosis virus (NPV) isolate HzS-15 using both polyclonal and monoclonal antibody screening. The gene was located within a Pstl-Sall fragment of the HzS 15 genome spanning from 96.5 to 97.3 m.u. Sequencing analyses revealed a long open reading frame of 927 nucleotides that predicted a protein of 37 kDa in size. Immunoblot analyses using the monoclonal antibody ENV409 demonstrated that the gene corresponded to a 40-kDa protein (p40) in SDS-polyacrylamide gels that was present exclusively in enveloped occluded virions but not in extracellular budded virions or envelope-stripped nucleocapsids. A p40 protein-specific transcript was detected at 16 hr postinfection in HzS-15-infected Hz 1075/UND-K cells and remained until 22 hr. Primer extension analyses demonstrated that the p40 protein specific transcript started at -49 nucleotides from the ATG start codon within an ATAAG consensus pentamer found in late protein genes of Baculoviruses. The deduced amino acid sequence of the HzS-15 p40 protein gene shared 44 and 45% sequence homology with the p40 proteins of Bombyx mori NPV and Autographa californica NPV, respectively. PMID- 8517019 TI - Detection and possible functions of African cassava mosaic virus DNA B gene products. AB - Polyclonal antisera raised against synthetic oligopeptides have been used to detect the DNA B gene products BV1 and BC1 of the geminivirus African cassava mosaic virus following SDS-PAGE fractionation of Nicotiana benthamiana extracts. BV1 antiserum detected a soluble protein of 29 kDa, consistent with the size predicted from sequence data. BC1 antiserum detected proteins of 37, 39, and 42 kDa in addition to variable, less abundant species, all of which are larger than the predicted size of 34 kDa. BC1 antiserum detected a single protein of 35-36 kDa following in vitro translation in reticulocyte lysate, suggesting that BC1 is post-translationally modified in plants. The nature of the modification was not resolved, although neither glycosylation nor association with nucleic acids is involved. In common with putative spread proteins of several other plants viruses, BC1 co-fractionated with the cell wall. The replication of both genomic components in N. tabacum protoplasts was unaffected by the introduction of frameshift mutations into BV1 and BC1 coding regions. In inoculated N. benthamiana leaves, however, the accumulation of a BV1 mutant was significantly reduced compared to the levels attained by co-inoculated, complementing BV1 and BC1 mutants. In contrast, the accumulation of a BC1 mutant was unaffected, although symptom induction in inoculated leaves and systemic infection occurred only in the presence of both BV1 and BC1. The results are consistent with a role for BV1 in localized cell-to-cell spread and for BC1, possibly together with BV1, in long-distance vascular spread of the virus. PMID- 8517020 TI - The roles of the red clover necrotic mosaic virus capsid and cell-to-cell movement proteins in systemic infection. AB - The red clover necrotic mosaic dianthovirus (RCNMV) genome is split between two single-stranded RNA species termed RNA-1 and RNA-2. RNA-2 is required for infection of whole plants but is dispensable for infection and virion formation in protoplasts. We have used full-length cDNA clones of RNA-1 and -2 from which infectious in vitro transcripts can be derived to construct a number of mutations in the RNA-1 encoded capsid protein and the RNA-2 encoded cell-to-cell movement protein genes. The capsid protein and the RNA sequence encoding the capsid protein were dispensable for infection of the inoculated leaves of Nicotiana benthamiana and N. clevelandii at both 15 and 25 degrees. In addition, capsid protein was not necessary for systemic infection of N. benthamiana at 15 degrees. As many as 39 amino acid residues could be deleted from the carboxyl-terminus of the RNA-2 encoded 35-kDa cell-to-cell movement protein without loss of or reduction in the rate of cell-to-cell movement or systemic infection. However, larger deletions within the cell-to-cell movement protein gene prevented cell-to cell movement and systemic infection of N. benthamiana. These data suggest that the spread of RCNMV in a systemic host is a combination of two distinct events: cell-to-cell movement and long distance transport. We conclude that the RCNMV 35 kDa movement protein is required for cell-to-cell movement, whereas the capsid protein is not necessary for cell-to-cell movement and, depending on host genotype and environmental factors, may or may not be required for long distance transport. PMID- 8517021 TI - Analysis of the role of 5' promoter elements and 3' flanking sequences on the expression of a baculovirus polyhedron envelope protein gene. AB - The polyhedron envelope protein gene of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV) is the third in a series of five open reading frames (ORFs 1-5) oriented in the same direction. Individual mRNAs initiate at conserved late gene promoter/mRNA start site (A/GTAAG) sequences located upstream of each ORF and the mRNAs co-terminate after the fifth ORF. To examine the influence of transcription from upstream promoter elements and the presence of an extensive 3' flanking sequence on the expression of the polyhedron envelope protein gene, the region was cloned into a phagemid vector and a BamHi site was inserted downstream of the ATG by site-directed mutagenesis and used for the insertion of a chloroamphenicol acetyl transferase (CAT) reporter gene. A set of clones were constructed in which individual or combinations of the late promoter elements from OFs 1, 2, and 3 were destroyed by site-directed mutagenesis. These plasmid constructs were transfected into Lymantria dispar cells infected with OpMNPV and cell extracts were assayed for CAT activity. Inactivation of the late promoter element immediately 5' of the polyhedron envelope protein gene led to a 96% decrease in CAT expression. Destruction of the ORF 2 late promoter element, or both the ORF 1 and ORF 2 late promoter elements, or deletion of the entire region containing ORFs 1 and 2 resulted in a 17 to 35% increase in CAT expression. In contrast, inactivation of the ORF 1 promoter alone resulted in no increase in CAT expression. Deletions of 3' flanking sequences of the polyhedron envelope protein gene caused major reduction in both CAT activity and steady-state levels of CAT mRNA. PMID- 8517022 TI - Minus sense transcripts of brome mosaic virus RNA-3 intercistronic region interfere with viral replication. AB - Interference with virus replication through the use of defective viral sequences is providing new insight to replication strategies and novel approaches for induced resistance. Because replication of brome mosaic virus (BMV) is potentiated by the intercistronic region of RNA-3, we examined the effect of adding various (-)sense RNAs corresponding to this region in co-transfections with wild type BMV RNAs. Progeny accumulation in barley protoplasts transfected with RNAs 1+2 was decreased by 90% in the presence of (-)RNA-3 delta HindIII, the longest (-)sense transcript tested, and by 85% when RNA-3 was also present. This trans interference was concentration dependent, and the use of deletion derivatives of (-)RNA-3 delta HindIII revealed that previously identified regulatory sequences within the intercistronic region were responsible for the observed interference. These deletion mutants were found to be of differing stabilities and several served as effective substrates for host-encoded polymerase to yield complementary (+)strands. Indeed, it is possible that the copying of viral RNA by the host polymerase serves as a hybrid arrest mechanism for discriminating against viral RNA functions. However, neither the ability of these sequences to serve as templates for host polymerase nor their (+)strand products contributed to the interference phenomenon, which may provide a new approach for engineering resistance to viral infection. PMID- 8517023 TI - Expression of simian type D retroviral (Mason-Pfizer monkey virus) capsids in insect cells using recombinant baculovirus. AB - Mason-Pfizer monkey virus (M-PMV) is a primate retrovirus that shows type D morphogenesis in mammalian cells. Immature intracytoplasmic A type particles (ICAPs) preassemble in the infected cell cytoplasm migrate to the plasma membrane and are released by budding. This is in contrast to retroviruses that show type C morphogenesis, where assembly and budding occur concurrently at the plasma membrane. We expressed the M-PMV structural genes (gag-pro-pol) in insect cells using a recombinant baculovirus. The polyprotein precursors assembled predominantly intracellularly, although a small proportion also assembled at the membrane. The protease enzyme was active since mature particles were identified in the culture supernatant. We also expressed the M-PMV mutants, D26N and gag STOP, which carry a nonfunctional protease or fail to express the protease gene, respectively. These baculovirus recombinants generated a homogeneous population of immature M-PMV capsids having exclusively type D morphogenesis. Sufficient quantities of polyprotein precursors were synthesized to be visualized directly on a Coomassie-stained protein gel, and the capsids were subject to purification. These results provide the first expression of type D retrovirus particles using the baculovirus expression system. PMID- 8517024 TI - Characterization of a nuclear retention sequence within the 3' region of the HIV 2 envelope gene. AB - During the phenotypic analysis of mutations in the HIV-2 envelope protein (gp140), we have identified a mutant that expresses high levels of gp140 in the absence of the Rev protein. This mutant was obtained by deletion of a 190-base pair fragment at the end of the env coding region. Northern blot analysis of RNAs produced by transfected HeLa cells showed that this fragment inhibits the cytoplasmic transport of unspliced env-specific RNAs in the absence of Rev. The "inhibitory element" was only active in the sense orientation and appeared to be specific for unspliced HIV-2 env RNAs, suggesting that it may have an important regulatory role for HIV-2 expression. PMID- 8517025 TI - The complete nucleotide sequence of parvovirus LuIII and localization of a unique sequence possibly responsible for its encapsidation pattern. AB - Parvovirus LuIII encapsidates single-stranded DNA of either plus or minus polarity with equal frequency, whereas the rodent parvoviruses MVMp and H-1 encapsidate minus strand DNA only. A full-length, infectious clone of LuIII was constructed and the complete nucleotide sequence of the genome was determined. Comparison of the LuIII sequence with those of MVMp and H-1 revealed that these viruses are virtually identical with respect to the genomic organization, location of regulatory signals, mRNA splicing patterns, and amino acid sequences of viral proteins. However, two regions of the LuIII sequence differ significantly from those of the rodent parvoviruses. At mu 92, LuIII has only one copy of a sequence found as a direct repeat in MVMp and H-1. Upstream of this sequence, at mu 89, there is an A-T-rich region, 47 nucleotides in length, unique to the LuIII genome. This A-T-rich region could represent a signal responsible for the totally different encapsidation patterns observed for these viruses. PMID- 8517026 TI - Human coronavirus OC43 RNA 4 lacks two open reading frames located downstream of the S gene of bovine coronavirus. AB - Nucleotide sequences between the spike (S) and membrane (M) protein genes of the OC43 strain of human corona-virus were obtained from PCR-amplified viral mRNAs. Sequence analysis of this region revealed the presence of two ORFs encoding proteins of 12.9 and 9.5 kDa. These two proteins were identified as putatively nonstructural (ns) due to their homology to the corresponding BCV ns gene products. Northern blot analysis indicated that each of these two genes was present on a separate mRNA (5 and 5-1, respectively). In vitro translation analyses demonstrated that the HCV-OC43 9.5-kDa protein, like its BCV counterpart, is poorly translated when situated downstream of the 12.9-kDa ORF, although immunofluorescence studies did confirm its presence in infected cells. Sequence analysis showed that a large portion of the 3'-end of the leader sequence is present within the viral genome, upstream of the 12.9-kDa ORF. In addition, two ORFs encoding potential 4.9- and 4.8-kDa ns proteins in BCV are absent in HCV-OC43, although a corresponding mRNA 4 was found at a very low level. These results demonstrate that these two putative ns proteins are not essential for virus replication, at least in HRT-18 cells. PMID- 8517027 TI - Primary HIV-1 isolates refractory to neutralization by soluble CD4 are potently inhibited by CD4-Pseudomonas exotoxin. AB - Despite the ability of soluble forms of CD4 (sCD4) and related CD4 derivatives to neutralize human immunodeficiency type 1 (HIV-1) infectivity in vitro, these agents have shown little evidence of efficacy in clinical trials with infected individuals. These disappointing findings may be related to recent observations that much higher concentrations of sCD4 are required for in vitro neutralization of primary HIV-1 isolates compared to laboratory-adapted strains. An alternative CD4-based therapeutic strategy exploits CD4 as a targeting agent to direct cytotoxic molecules to selectively kill HIV-infected cells. In this report we demonstrate that CD4-Pseudomonas exotoxin inhibits spreading infection by primary HIV-1 isolates known to be highly refractory to neutralization by soluble CD4; the observed potency is at least as great as for a prototypic sCD4-sensitive, laboratory-adapted HIV-1 strain. Thus, the in vitro efficacy of a CD4-based agent, which acts by targeted killing of infected cells, appears not to be compromised by features which render primary HIV-1 isolates refractory to neutralization by sCD4 derivatives. These results have important conceptual and practical implications for CD4-based therapeutic strategies. PMID- 8517028 TI - Regulation of the late events in flavivirus protein processing and maturation. AB - In order to determine the requirements for secretion of flavivirus structural proteins, we analyzed the expression of several West Nile flavivirus gene cassettes of different lengths in vaccinia virus expression systems. Expression of the longest cassette coding for the 5'-nontranslated region, proteins C through NS2B, and the protease domain of NS3, resulted in secretion of prM-E complexes and cleavage of prM. The presence and proper processing of the NS2A NS2B-NS3 region appeared to be necessary for prM-E secretion. These proteins were released from cells mostly as membranous complexes which may represent empty viral envelopes. Cleavage of the membrane-associated intracellular form of protein C (C(i)) to produce the virion form (Ce) appeared to be critical for release of viral proteins. The presence and proper cleavage of the NS2A-NS2B-NS3 region were also found to be necessary for efficient C-prM cleavage by signalases. The NS2B-NS3 complex was implicated in cleavage of the intracellular form of protein C. Formation of a low level of virus-like particles was detected by electron microscopy. A model for virion formation, suggesting a critical role of the NS2B and NS3 proteins, is discussed. PMID- 8517029 TI - A baculovirus encoded 16-kDa glycoprotein localizes near the nuclear membrane of infected cells. AB - An open reading frame (ORF 2) located upstream of the polyhedron envelope protein gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) was cloned in frame into a trpE expression vector. The fusion protein produced by this construct was used for the production of a monospecific antiserum. Western blot analysis of OpMNPV-infected Lymantria dispar cells detected a 16-kDa protein at 24 hr postinfection. The 16-kDa protein was determined to be N-glycosylated by tunicamycin treatment of infected cells. Immunofluorescence microscopy localized the 16-kDa protein to foci of intense cytoplasmic staining near the nuclear membrane. Immunoelectron microscopy indicated that the 16-kDa protein is associated with lamellar-like structures peripheral to the nuclear membrane and with envelopes of virus that have budded into the cytoplasm. The 16-kDa protein was not associated with extracellular budded or polyhedron-derived virions. PMID- 8517030 TI - Determination of the position of the boundaries of the terminal repetitive sequences within the genome of molluscum contagiosum virus type 1 by DNA nucleotide sequence analysis. AB - The repetitive DNA sequences of the genome of Molluscum contagiosum virus type 1 (MCV-1) have been localized within the terminal regions of the viral genome corresponding to the BamHI MCV-1 DNA fragments B (18 kbp; 0 to 0.095 map units (m.u.)) and E (10.5 kbp; 0.944 to 1 m.u.). The fine mapping of these particular regions of the genome of MCV-1 revealed that the boundaries of the terminal repetitive DNA sequences of the viral genome are located within the DNA sequences of the HindIII MCV-1 DNA fragments K (3.8 kbp; 0.014 to 0.036 m.u.) and J1 (4.1 kbp; 0.962 to 0.985 m.u.). The exact position of the boundary of the repetitive DNA sequences was determined by DNA nucleotide sequencing. The HindIII DNA fragments K and J1 compose 3859 and 4107 bp, respectively. The DNA sequences of HindIII MCV-1 DNA fragment K possess repetitive DNA sequences between the nucleotide positions 1 and 1675 which are homologous to the inverted and complementary DNA sequences of the HindIII MCV-1 DNA fragment J1 between the nucleotide positions 2437 and 4107 (1670 bp). The degree of DNA sequence homology detected between the repetitive DNA sequences in the HindIII DNA fragments K and J1 of the viral genome was found to be 98%. The number of open reading frames (ORFs) detected by the analysis of the DNA sequences of the HindIII MCV-1 DNA fragments K and J1 was found to be 14 (70 to 219 amino acid residues) and 11 (70 to 365 amino acid residues), respectively. PMID- 8517031 TI - Presence of env genes in members of the RTVL-H family of human endogenous retrovirus-like elements. AB - We have found that the RTVL-H family of human endogenous retrovirus-like elements was highly expressed in lung squamous cell carcinoma tissue and several human cell lines. We determined the nucleotide sequences of several cDNA clones and found a unique sequence that was not present in the published "prototypic" RTVL-H sequence. An open reading frame in this region encoded an amino acid sequence homologous to the conserved sequence in the transmembrane envelope protein of various retroviruses. Two genomic clones that encoded this sequence were obtained and sequenced. One RTVL-H element containing the env gene was 8.7 kilobase pairs in length. The putative env gene, consisting of about 1800 base pairs, had two open reading frames interrupted by a termination codon. The amino acid sequence of this region showed significant homology with those of other retroviral envelope proteins and contained eight potential glycosylation sites. There were estimated to be about 100 copies of RTVL-H elements containing the env gene per haploid human genome. PMID- 8517032 TI - Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV. AB - The genome of Lelystad virus (LV), the causative agent of porcine epidemic abortion and respiratory syndrome (previously known as mystery swine disease), was shown to be a polyadenylated RNA molecule. The nucleotide sequence of the LV genome was determined from a set of overlapping cDNA clones. A consecutive sequence of 15,088 nucleotides was obtained. Eight open reading frames (ORFs) that might encode virus-specific proteins were identified. ORF1a and ORF1b are predicted to encode the viral RNA polymerase because the amino acid sequence contains sequence elements that are conserved in RNA polymerases of the torovirus Berne virus (BEV), equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), the coronaviruses, and other positive-strand RNA viruses. A heptanucleotide slippery sequence (UUUAAAC) and a putative pseudoknot structure, which are both required for efficient ribosomal frameshifting during translation of the RNA polymerase ORF1b of BEV, EAV, and the coronaviruses, were identified in the overlapping region of ORF1a and ORF1b of LV. ORFs 2 to 6 probably encode viral membrane-associated proteins, whereas ORF7 is predicted to encode the nucleocapsid protein. Comparison of the amino acid sequences of the ORFs identified in the genome of LV, LDV, and EAV indicated that LV and LDV are more closely related than LV and EAV. A 3' nested set of six subgenomic RNAs was detected in LV-infected cells. These subgenomic RNAs contain a common leader sequence that is derived from the 5' end of the genomic RNA and that is joined to the 3' terminal body sequence. Our results indicate that LV is closely related evolutionarily to LDV and EAV, both members of a recently proposed family of positive-strand RNA viruses, the Arteriviridae. PMID- 8517034 TI - Replication of maize streak virus mutants in maize protoplasts: evidence for a movement protein. AB - We have used protoplasts derived from a maize (Black Mexican Sweet) suspension culture to study the replication of maize streak virus (MSV) wild-type (wt) and mutant DNA genomes. Following inoculation with plasmids containing multimeric copies of MSV, both single-stranded (ss) and double-stranded MSV DNA forms were produced, in proportions relative to those seen in infected plants. The immunodetection of coat protein (PV2) and geminate particles confirmed that the protoplasts were able to support the entire multiplication cycle of MSV and therefore were suitable for the study of MSV gene function. Inoculation of protoplasts with V1 gene mutants which are unable to produce systemic infections in plants resulted in DNA replication and encapsidation indistinguishable from that obtained with wt constructs implicating the protein in virus movement. Computer analysis of the V1 protein (PV1) indicated a potential trans-membrane or membrane-embedded domain. Following inoculation of protoplasts with V2 mutants, ssDNA was not detected; the inability of these mutants to spread in plants may be due to a lack of ssDNA, PV2, or a combination of the two. The requirements for systemic infection of MSV are discussed. PMID- 8517033 TI - Adenovirus type 40 virions contain two distinct fibers. AB - Human subgroup F adenoviruses, types 40 and 41, have two genes that could specify different fiber proteins, a long fiber with 21 or 22 pseudorepeat motifs in the shaft, and a short fiber with 12 motifs. We show that for adenovirus type 40, both proteins are expressed from separate late regions of the genome. They are incorporated into the virion with only one fiber per penton base, unlike avian adenoviruses which have two fibers extending from each penton. Comparison of known adenovirus fiber sequences suggests that the two fibers in adenovirus 40 and 41 arose through an external recombination event rather than having evolved from each other directly. Two alternative fibers on the virion may imply the existence of two distinct receptors. PMID- 8517035 TI - Location of two putative origins of DNA replication of Autographa californica nuclear polyhedrosis virus. AB - Previously, we described a defective Autographa californica nuclear polyhedrosis virus (AcMNPV) which must contain cis-acting elements required for DNA synthesis, such as the origin(s) of replication (ori). Defective genomes of AcMNPV generated after serial undiluted passage were analyzed further. Three small separated regions were retained in DNA of defective AcMNPV and accumulated in extracellular defective interfering viruses as well as in intracellular DNA after 40 passages. Two of these regions have now been identified as containing putative ori. They are located on the HindIII-B fragment between map units (m.u.) 50.1 and 53.2 and on the HindIII-Q fragment between m.u. 87.2 and 88.9 of the physical map of AcMNPV DNA, respectively. Transfection of Spodoptera frugiperda cells with plasmids containing these sequences followed by superinfection with intact helper AcMNPV resulted in amplification of these plasmids, as demonstrated by the Dpnl sensitivity assay. The replicating activity of HindIII-Q is putatively located within the 1000-bp region containing a highly repetitive DNA (hr5), which is also ascribed to enhance delayed-early gene expression. In order to demonstrate replicating activity of test plasmids, it appeared essential to transfect the cells well before superinfection with helper virus. PMID- 8517036 TI - [Arterial hypertension in clinical practice]. AB - Based on their epidemiological survey in the South Moravian region where 64,083 men and women, mean age 43.1 years, were examined, the authors submit the results of screening, prevalence, control and complications of hypertension. They draw attention to the high rate and almost 50% detection of new patients, in particular of productive age. The results indicate the high risk of arterial hypertension in the genesis of cerebrovascular and cardiovascular disease, on the inadequate control of the disease in field practice and the favourable effect on the prevalence of cerebrovascular disease when effective therapy is used, as apparent from a five-year perspective study. The authors emphasize the significant role of secondary prevention on the course, prognosis and complications of this disease of the circulation. PMID- 8517037 TI - [Isolated hematuria in adolescents and adults. The value of renal biopsy]. AB - In 103 subjects with asymptomatic isolated haematuria (persisting for more than 6 months in the absence of proteinuria, bacteriuria, impaired haemocoagulation or urological disease) renal biopsy was performed. The mean age of the patients was 25.2 years, range 14-58 years. In 94% glomerular changes were detected--most frequently minimal glomerular lesions (67%) and proliferative mesangial glomerulonephritis (15%). Focal segmental proliferative glomerulonephritis was rare (4%). Immunofluorescent examination revealed IgA nephropathy in 40% (all cases of diffuse and focally segmental proliferative glomerulonephritis and one quarter of minimal glomerular lesions). Changes of tubules and interstitium were recorded in 26%, with the exception of one patient they were always associated with glomerular affection. From the investigation ensues that the predominating cause of isolated asymptomatic haematuria, not clarified by non-invasive examination, is usually not serious and is an affection frequently associated with tubulointerstitial changes. As many as 40% of isolated cases of haematuria may be the manifestation of IgA nephropathy. The deposition of IgA is more frequently associated with a more advanced grade of glomerular affection. Indication of diagnostic renal biopsy in isolated haematuria remains individual. PMID- 8517038 TI - [Energy expenditure at rest in patients with active rheumatoid arthritis and malnutrition]. AB - Malnutrition is found significantly more often in patients with rheumatoid arthritis than in the normal population. One of the contributing causes may be the elevated energy expenditure at rest found in the stage of increased activity of the disease. The aim of the present work was to evaluate the association between the activity of the disease, the presence of signs of malnutrition and the energy expenditure at rest. In 26 patients with rheumatoid arthritis stage I IV, mean age 62.2 +/- 11.0 years the basic parameters describing the activity of the disease were assessed (sedimentation rate, C-reactive protein (CRP), the articular index according to Thompson) and the nutritional status (body mass index, total serum protein and albumin, the skinfold above the triceps, the circumference of the muscles of the arm). In all patients indirect calorimetry at rest on fasting was applied. The assessed value of the energy expenditure at rest (REE) was expressed as % BMR calculated according to the formula of Harris Benedict. In the group of patients with a higher activity of the disease (CRP positive, n = 14) REE was significantly higher as compared with the other patients (109.4 +/- 13.3% vs. 98.7 +/- 9.3%, p < 0.05). In patients who suffered from obvious depletion of visceral protein (albumin less than 30 milligrams, n = 5) REE was significantly higher than in the remainder (117.8 +/- 13.8% vs. 101.3 +/- 10.4%, p < 0.05). In the whole group there was a less close, though statistically significant correlation between CRP and REE (correlation coefficient 0.463, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517039 TI - [Ambulatory therapy of internal hemorrhoids using infrared photocoagulation and elastic ligature]. AB - The authors present their experience with infrared photocoagulation and its combination with suction ligature by means of elastic rings in the treatment of internal haemorrhoids. They used infrared photocoagulation in 15 patients with grade I haemorrhoids, the procedure was painless in 80% and 20% of the patients reported mild pain. As to side-effects, 13.3% reported mild discomfort during defaecation. After one month 66.6% were symptom-free, 26.7% improved and 6.7% did not report improvement. The authors used the combination of suction ligation and infrared photocoagulation in 27 patients with internal haemorrhoids grade II. The procedure was painless in 70.4%, slight pain was reported by 25.9% and in one patient the procedure was associated with severe pain (3.7%). No side-effects were reported by 44.4% of the patients, mild discomfort during defaecation in 48.2% and more marked discomfort in 7.4%. None of the methods were associated with haemorrhage. After one month 74.1% of the patients were asymptomatic, 18.5% reported improvement and two probands (7.4%) did not report improvement. These methods can be used, due to the simple procedure, slight discomfort caused to the patients and low incidence of side-effects in out-patients departments. The short time taken by the procedure and the low cost are not negligible either. PMID- 8517040 TI - [Metabolic and humoral characteristics of normotensive offspring in a family with a history of essential hypertension]. AB - Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications. PMID- 8517041 TI - [What are the characteristic signs of cholecystolithiasis in patients with type 2 diabetes?]. AB - In a group of 166 patients with type 2 diabetes mellitus, hospitalized at the First Medical Clinic, Faculty Hospital Prague 5-Motol, cholecystolithiasis was found in 91. In these patients sonographic parameters were analyzed. All were hospitalized primarily on account of a non-biliary indications. The group comprised 67 men, mean age 69 years. The control group was formed by 67 patients with a normal glucose tolerance. An enlarged gallbladder was found in 15 patients (16.4%), a gallbladder of reduced size in 8 (8.8%). Stones smaller than 1 cm were in the group of diabetics in 31 subjects (34.3%), stones larger than 1 cm in 60 (65.7%). A wall of the gallbladder wider than 3.5 mm was found in 14 (15.4%) diabetics with cholecystolithiasis. All these results were statistically significant as compared with the control group (p < 0.01). There was no significant difference in the number of stones in diabetics and controls. The authors discuss the causes of these findings. In the conclusion the authors state that it is necessary to seek actively cholecystolithiasis in type 2 diabetics and indicate cholecystectomy in time to prevent numerous, in particular inflammatory, complications. For detection ultrasonography is suited best. PMID- 8517042 TI - [Determination of HLA-B27 antigen subtypes from the results of lymphocyte reactions to anti-HLA-B27 sera]. AB - Forty-five specimens of lymphocytes from HLA-B27 positive subjects were examined by the micro-lymphocytotoxic test with 48 anti-HLA-B27 sera and the results were evaluated statistically by calculation of the correlation coefficient r. Based on the results of the statistical evaluation two groups of sera were determined which determined two groups of lymphocytes, carriers of different HLA-B27 subtypes. Six sera determined subtype B27P1, detected in four lymphocyte samples, another six sera subtype B27P2 found in three lymphocytes. The results of the statistical evaluation correspond to the serological reactions. The results indicate that HLA antigens can be reliably differentiated by simple methods. PMID- 8517043 TI - [A rare occurrence of familial idiopathic pulmonary fibrosis]. AB - The author describes rare familial incidence of idiopathic pulmonary fibrosis. The disease occurred and was the cause of death in all three children under five years--the patient's daughters. The patient contracted the disease at the age of 59 years. When modern treatment is used, the course of the disease is so far favourable. The author discusses aetiopathogenetic and hereditary aspects of idiopathic pulmonary fibrosis. He reminds of contemporary possibilities of diagnosis of this rare but very serious pulmonary disease. PMID- 8517044 TI - [Behcet's disease and IgG lambda paraproteinemia]. AB - The authors describe the clinical observation and therapeutic experience of the seven-year follow-up of a female patient with Behcet's disease according to the diagnostic classification criteria of the International Study Group (1990). The remarkable feature of the described observation is evidence of the herpes simplex virus type I in the oral cavity and in particular the five-year follow-up of stabilized paraproteinaemia IgG lambda of obscure impact. PMID- 8517045 TI - [Angiologic findings in type 1 diabetics who have had diabetes longer than 25 years]. AB - The authors present a group of type 1 diabetics with duration of IDDM longer than 25 years (15 men and 10 women), mean age 53.8 years, mean duration from diagnosis of IDDM 35.0 years. The authors performed angiologic examination by using noninvasive methods with focus on affections of extracranial carotid arteries and peripheral arteries by using ultrasonographic methods and by measuring skin perfusion pressure by the photocell of the plethysmograph on the fingers of lower extremities. The authors investigated the subsequent risk factors--obesity, smoking, hypertension, hyperlipoproteinaemias, ischaemic heart disease, strokes. Macroangiopathy of lower extremities was detected in 28.5%, hemodynamically nonsevere stenosis of the extracranial carotid arteries in 20% of patients. As a result, the authors emphasize the need for regular control of arterial changes in diabetics of type 1. PMID- 8517046 TI - [Ultrasonography in the diagnosis of lung diseases]. AB - Ultrasonographic examination of the chest despite limiting factors holds an important place in the diagnosis of pulmonary diseases. In the submitted paper the author describes in detail in addition to indications of ultrasonographic examination, ultrasonographic findings in pathological processes--a free and encapsulated pleural exudate, empyema, tumours of the lungs and pleura, haemothorax, atelectasis of the pulmonary parenchyma. In the ultrasonographic picture the author evaluated the echogenity of the finding, the presence of septa, fibrin fibres and spirals, the presence of different loculations. The authors reached the conclusion that, based on the mentioned data, it is possible to assess more rapidly and more accurately the character and aetiology of the pathological finding. PMID- 8517047 TI - [Little known paraneoplastic syndromes]. AB - The author describes briefly some little known paraneoplastic syndromes: hypertension, circulatory failure, arterial ischaemia, Stauffer's syndrome, visceral neuropathy, thyroiditis and others. He comments on them, based on his own experience. PMID- 8517048 TI - Clinical evaluation of viral safety of coagulation factor VIII and IX concentrates. AB - Virucidal methods to inactivate infectious agents are based on various methods of heating or chemically treating plasma concentrates of coagulation factors VIII and IX used in the treatment of hemophilia A and B. This clinical evaluation of the viral safety of such 'treated' concentrates is mainly based on the prospective study of previously untreated hemophiliacs by means of clinical and serological markers of viral infection. Although there have been a few focal episodes of human immunodeficiency virus (HIV) transmission by clotting factors, these have been traced to ineffective virucidal methods that are no longer used or to clerical errors during the manufacturing process. Viral inactivation by pasteurization, vapor heating, heating in the lyophilized state at 80 degrees C and addition of solvent/detergent definitely decreases the risk of infection with hepatitis B and C. The current screening of plasma units for antibody to hepatitis C virus prior to inclusion in pools for concentrate production should further decrease the risk of hepatitis C infection. Other viruses, such as parvovirus and the hepatitis A virus, may still cause infections because they are quite resistant to virucidal methods. On the whole, virucidal methods have greatly reduced the risk of new HIV infections and, to a lesser degree, hepatitis. PMID- 8517050 TI - Influence of granulocyte antibodies on granulocyte function. AB - The following substances were tested for their influence on granulocyte function: 8 sera that contained human granulocyte-specific alloantibodies against the antigens NA1, NA2 and NB1, two HLA antisera, and the monoclonal antibodies W6/32 and CLB-FcR-gran 1. The effects examined included spontaneous and directed migration, immune phagocytosis inhibition and the generation of oxygen radicals. Using the under-agarose technique, spontaneous migration of sensitized granulocytes was normal. For all antibodies tested, the chemotactic index for N fMLP, LTB4 and opsonized zymosan was greater than 1. Granulocyte immune phagocytosis of sensitized sheep red blood cells was strongly inhibited by all alloantisera and monoclonal antibodies. The generation of oxygen radicals after triggering the respiratory burst with sensitized sheep red blood cells was also strongly inhibited in the chemiluminescence assay. Immune phagocytosis and chemiluminescent response of granulocytes lacking the corresponding antigen of the tested alloantibodies were not affected. Since sensitization of neutrophils with F(ab')2 fragments of the monoclonal antibodies W6/32 and CLB-FcR-gran 1 showed lower inhibition of generation of oxygen radicals after triggering, Fc dependent interaction with the target cells seems to be necessary for inhibition. Our results suggest that binding of NA1-, NA2- or NB1-specific alloantibodies to granulocytes not only causes neutropenia, but also impairs granulocyte function. PMID- 8517049 TI - Comparison of anti-human and anti-porcine factor VIII inhibitor levels in 63 patients with severe haemophilia A. A French Multicentric Study. AB - The levels of anti-human and anti-porcine factor VIII inhibitors, measured in 63 severe haemophilia A patients, lay in the ranges of < 0.2-2,600 and < 0.2-1,300 Bethesda units per ml (BU/ml), respectively, with a median cross-reactivity of 33%. In 4 patients, human and porcine inhibitor levels were determined using both plasma, either human or porcine, and factor VIII concentrate, either very high purity human or porcine (Hyate:C). A good correlation between titres was found, whatever the source of factor VIII (plasma or concentrate). The cross-reactivity varies from 0 to over 100%, indicating that the evaluation of both human and porcine inhibitors should be mandatory before any treatment with Hyate:C. Results show that of the 46 patients with human inhibitor of more than 5 BU/ml, 21 (46%) with a low porcine inhibitor (< 5 BU/ml) could benefit from Hyate:C. PMID- 8517051 TI - Maternal CW alloimmunization. AB - The Winnipeg Rh Laboratory has reviewed its experiences with maternal CW alloimmunization. From September 24, 1956, to March 31, 1992, 12 women with significant CW alloimmunization underwent 18 pregnancies. In 3 (4 pregnancies) the antibody, despite its strength, was 'naturally occurring' (i.e. there was no known exposure to CW-positive red cells). The remaining 9 women (14 pregnancies) had CW-positive husbands. Two had CW-negative babies and a third infant, probably CW negative, was stillborn and macerated at 43 weeks gestation. Eleven babies were CW positive and had hemolytic disease of the newborn (HDN), with antiglobulin-positive red cells. Five did not require treatment; 2 needed phototherapy only, and 4 (born between 1956 and 1963) required exchange transfusions. No anti-CW screening was carried out until 1977; thereafter it was sporadic, 11 of 51 screening red cells being CW positive in the 39-month period ending March 31st, 1992. From November 1, 1977, to March 31, 1992, 24 women (30 pregnancies, 31 conceptuses) with insignificant anti-CW alloantibodies were identified. Extrapolating these figures to the entire period from September 24, 1956, to March 31, 1992, we estimate that at least 430 women (at least 573 pregnancies) were CW alloimmunized, most of the antibodies being 'naturally occurring'. Only 2% of the conceptuses were CW positive and affected; none were severely affected. Anti-CW is relatively common, occurring in about 1 pregnant Manitoban woman in 1,100. On very rare occasions (11 times in Manitoba in 36 years and 5 months) anti-CW HDN occurs which, although not severe, may end in kernicterus with brain damage or neonatal death unless it is detected promptly and treated appropriately. PMID- 8517052 TI - Platelet cryopreservation using dimethylsulfoxide/polyethylene glycol/sugar mixture as cryopreserving solution. PMID- 8517053 TI - Avoiding indeterminate results in HIV-1 western blot using synthetic peptide assays. HIV-2 Spanish Study Group. PMID- 8517054 TI - Quality of commercial antibody screening red cells. PMID- 8517055 TI - Successful transfusion of Yka-positive red cells in a patient with anti-Yka. PMID- 8517056 TI - [Combination therapy with recombinant interferon alpha-21 (rIFN alpha 2a) and recombinant interleukin 2 (rIL-2) in metastatic renal cell cancer]. AB - Sixteen patients with histologically-proven metastatic renal cell carcinoma (RCC) were treated after nephrectomy with a daily continuous 24-hour i.v. infusion of recombinant human interleukin-2 (rIL-2) at a dosage of 18 x 10(6) IU/m2 daily for 5 days per week and of recombinant interferon alpha-2a (rIFN-alpha 2a) 5 x 10(6) IU/m2 subcutaneously on days 2 and 4. The treatment cycles were repeated at 3 weekly intervals. Altogether 38 treatment cycles were given, but only 14/16 patients were evaluable for response rates. The main toxic side effects were fever, nausea, chills, anorexia, hypotension and hepatotoxic syndrome (Toxicity grades I-III, WHO). There were 3 objective responses among the 14 evaluable patients (21%); 2 patients have remained in complete remission for 12 and 8 months, respectively until now whilst 1 has shown a partial response for 21 months. PMID- 8517057 TI - [A questionnaire suitable for general practice for detection of the health status and quality of life of patients with hemato-oncologic diseases: psychometric properties. The Study G "Quality of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.)]. AB - In the evaluation of therapeutic measures it is important to consider the consequences of the proposed treatment on the subjective quality of health and the subjective quality of life. Since no adequate instrument existed to provide such assessments, a short, theoretically based questionnaire was developed and psychometrically tested. The construction phase was based on data of 104 adults with haemato-oncological diseases, leading to the design of a questionnaire which was tested using data of a further 292 patients. The validity of the "questionnaire for attitudes towards quality of health and quality of life" was assessed by comparing it with physicians' ratings and by correlation with the results of an extensive questionnaire. The reliability was satisfactory; the questionnaire met with high acceptance by patients, physicians and health care personnel. It complies with the requirements of clinical trials where the objective is to measure quality of health and quality of life. PMID- 8517058 TI - Association between neopterin and beta-2-microglobulin levels and HIV status in Romanian orphanage children. AB - Serologic markers of immune activation, neopterin and beta-2-microglobulin (B2M), have been shown to predict progressive human immunodeficiency virus type 1 (HIV 1) disease based on cohort studies in adults. Both parameters appear also to be valuable in distinguishing HIV-1 infants with progressive disease from asymptomatic infants and HIV-1 seronegative infants. In a cross-sectional study we examined the utility of neopterin and B2M testing in 135 infants of an orphanage in Romania, 69 of the infants (51%) were found to be HIV-1 antibody seropositive; 95% of the 135 infants were either hepatitis B virus (HBV) antigen or antibody seropositive. In the HIV-1 seronegative infants B2M was higher in those with HBV antigenaemia. Serum neopterin and B2M concentrations were higher in HIV-1 seropositive than in seronegative infants (p = 7 x 10(-12) and 1 x 10( 6)). Children with CDC stage P2 had only slightly higher neopterin and B2M values as compared to stage P1 (P = 0.04 and 0.08). Our study indicates that measurement of neopterin and B2M is useful to monitor HIV-1 infection, particularly in areas where laboratory facilities are limited. Both parameters continue to be associated with HIV-1 infection even when there is a high background rate of other infections. PMID- 8517059 TI - [Effect of cytokines on HIV infection in cell lines]. PMID- 8517060 TI - [Letter on the topic of "cancer and the psyche"]. PMID- 8517061 TI - [Clinical and EEG/ERP brain mapping studies with vigabatrin in therapy refractory epileptic patients]. AB - In a single blind study the antiepileptic effects and safety of vigabatrin--a new anticonvulsant drug selectively inhibiting GABA-transaminase--was investigated in therapy resistant epilepsy, along with its central effects objectivated by mapping of EEG and event-related potentials (ERP). In addition to their current antiepileptic therapy, 10 patients with complex partial seizures (CP) (4 male, 6 female), aged between 22 and 57 years received placebo for 1 month, subsequently 2 g vigabatrin for 2 months and thereafter a titrated optimal dosage vigabatrin for another 2 months. Clinical investigations were carried out at the afore mentioned periods, neurophysiological ones pre and post 2 months vigabatrin. After 2 months vigabatrin, 5 out of 10 patients had a 50% or greater decrease in CP frequency, after another 2 months 7 out of 10. The median number of CP per months decreased from 5.5 to 3.75 (p < 0.05) to 2.0 (p < 0.01), respectively. No clinically relevant side effects and laboratory changes were noted. EEG mapping showed decreased fast alpha and slow beta power and increased delta-theta frequency variability, reflecting most likely a decreased CP disposition. ERP mapping showed slightly increased N1 and P2 as well as reduced P300 amplitudes. Unchanged P300 latency indicated no delayed stimulus evaluation time after vigabatrin therapy. PMID- 8517062 TI - [An analysis of the clinical effectiveness of manual therapy in cervical vertebrae syndrome]. AB - The aim of this review was to evaluate the clinical effectiveness of manipulation techniques as a therapy for cervical pain syndromes. Only few randomized trials have been published on this matter. They come to contradictory conclusions. In this unclear situation, the prescribing physician should note that there is no scientific evidence to suggest that manipulations are superior to other forms of treatment, for instance exercise therapy. Further research in this area seems therefore mandatory. PMID- 8517063 TI - [Cerebellar hemorrhage and cerebellar infarct: retrospective study of 125 cases]. AB - In a retrospective study of 125 patients, symptoms, diagnosis, and clinical course of 64 cases of cerebellar infarction and 61 cerebellar hemorrhage were studied retrospectively. Neurologically, cerebellar signs were present in 50% of hemorrhages and 7%, of infarctions, while 50% of patients with cerebellar hemorrhage and 37% of patients with cerebellar infarction showed brain stem symptoms or cranial nerve deficits; at least slight disturbance of consciousness was present in all patients. The state of consciousness, as estimated by the Innsbruck Coma Scale, together with diagnostic imaging (CT and/or MRT) allowed precise indication for surgical intervention. Over-all lethality was 11% for cerebellar infarction, and 31%, for cerebellar hemorrhage. Comparison of clinical outcome and state of consciousness at time of surgery suggests, that decompressive craniotomy should be performed even in deeply comatose patients with signs of decerebration. PMID- 8517064 TI - [Screening for risk factors in agricultural schools of 5 Austrian federal counties ]. AB - While screening activities have already been performed in a wide range in adults in Austria, extensive investigations in children and juveniles have so far only been done in a very limited number. In 1094 out of 1732 juveniles attending agricultural schools all lipid parameters were fully documented and thus could be evaluated. On an average, the total cholesterol (169 mg/dl) was too high; the worst findings for lipid parameters cholesterol, HDL-cholesterol, triglycerides, apolipoprotein-A1 were found in pupils of Burgenland. The cholesterol/HDL cholesterol ratio in Burgenland was significantly (p < 0.01) higher than in Lower Austria. Female participants had a higher total cholesterol, HDL-cholesterol, and apolipoprotein-A1, but lower triglycerides and also lower blood pressure. Juveniles with a positive family history showed lower total cholesterol, but higher triglycerides as well as HDL-cholesterol. In heavy smokers, but also in occasional smokers, a lower total cholesterol, but decreased HDL-cholesterol and apolipoprotein-A1 and increased triglycerides were found. These findings underline the high prevalence of hypercholesterolemia in juveniles justifying screening activities and possibly therapeutic intervention at this young age. PMID- 8517065 TI - [The value of 2-dimensional echocardiography in conjunction with various exercise tests for diagnosis of myocardial ischemia]. AB - In 16 persons of the control group (group I) and in 27 patients with coronary heart disease (group II) value of two-dimensional echocardiography was determined combined with exercise, transoesophageal left atrial pacing, dipyridamole and cold pressor tests in detecting myocardial ischaemia. Changes of ST-segment in the ECG, left ventricular ejection fraction and wall motion in the 11 segments were studied during the tests. Sensitivity, specificity and predictive value confirming and excluding ischaemic heart disease of the analyzed parameters were determined. The sensitivity and the specificity of exercise, left atrial pacing, dipyridamole and cold pressor tests during the analysis of ST-segment were 70%, 81%, 37%, 4% and 62%, 67%, 94%, 100%, respectively. Two-dimensional echocardiography analysis did not increase the diagnostic value of the exercise and left atrial pacing tests, whereas the diagnostic value of dipyridamole and cold pressor tests were increased. PMID- 8517066 TI - [Emergency equipment for the physician]. AB - In case of an emergency it is the moral and legal obligation of every physician render first aid. For immediate and effective prehospital treatment a certain minimum of medical equipment should be available. In this article, drugs and essential technical equipment of a doctor's first aid kit are recommended which has proved useful in the management of respiratory and cardiovascular emergencies. Monitoring of vital functions as well as the emergency treatment itself require technical equipment. The proposed essential equipment allows every first-aid doctor--beyond simple measures of basic life support--to reverse life- threatening derangements of vital organ systems and to save time before definite treatment in the hospital. PMID- 8517067 TI - [Increased level of nitrogen radicals in serum of patients with rheumatic diseases and AIDS]. AB - 354 sera from venous blood of patients with various rheumatic diseases and AIDS were assayed for the presence of reactive nitrogen intermediates. Compared to healthy individuals, the serum levels of nitric oxides from patients with connective tissue diseases and inflammatory rheumatic diseases were elevated (P < 0.01) by 170-600% and those from HIV-infected patients by 220%. PMID- 8517068 TI - [Sauna therapy in coronary heart disease with hypertension after bypass operation, in heart aneurysm operation and in essential hypertension]. AB - It is reported about the influence of the sauna therapy on blood pressure, heart frequency, peripheric hemodynamics (Xenon-133-muscle-clearance) and the reaction of the cardiac output or left ventricular ejection fraction with hypertonia patients, patients with coronary heart disease (CHD) and hypertension and after aneurysm resection after heart infarction. It was shown that sauna therapy has a positive effect on hypertonic regulations troubles. One of the reasons of lowering blood pressure is the significant improvement of the peripheral hemodynamics. Sauna therapy does not result in any improvement of the left ventricles pumping function after operation. All described groups of patients showed a good tolerance and compliance with sauna therapy. PMID- 8517069 TI - [250 years ago: the origin of electrotherapy exemplified by Halle]. AB - Experiments started in 1743 by a working group at the university of Halle marked the beginning of efforts to incorporate electricity into clinical therapy. Very soon this resulted in knowledge that was also taken up elsewhere, leading to a period of intensive research. The creative suggestions that originated in Halle were authored, among others, by Johann Gottlob Kruger, Christian Gottlieb Kratzenstein and Johann Joachim Lange. Their experimental and clinical findings were accompanied by deliberations on the mechanism of action of electrotherapy on which they reported in detail. Due to adverse circumstances this initially leading position occupied by Halle faded out already shortly after the middle of the century. PMID- 8517070 TI - [Diagnosis and therapy of diabetic polyneuropathy]. AB - Distinction is made between peripheral and autonomic neuropathy. The former is usually painful, while the latter is especially associated with cardiovascular, gastrointestinal and urogenital disturbances. In the diagnosis of peripheral neuropathy, a basic neurological examination (reflex status, vibratory sense) takes precedence over measuring the velocity of nerve conduction and determining the temperature and pain thresholds. The diagnostic approach to the autonomic disturbances is organ-specific (testing of cardiovascular reflexes, sonographic and scintigraphic determination of gastric emptying, infusion urography and uroflowmetry). Early diagnosis and optimal diabetes control are the therapeutic consequences. Symptomatic treatment includes the administration of analgesics, antidepressants and carbamazepine. A newer drug being currently tried is mexiletine. High doses of alpha-liponic acid as well as the fat-soluble B vitamins are used for causal therapy. Clinical trials with aldose reductase inhibitors and gamma-linolenic acid are under way. PMID- 8517071 TI - [Myosonographic findings in inflammatory muscular diseases]. AB - Inflammatory myopathies are rare diseases with an annual incidence of about 1-8 per 1 million persons. However, they are of special importance in myology as they can be treated successfully. There are auto-immune mediated and infectious forms of myositis. From the clinical and myopathological view, one can distinguish acute and chronic forms: the former presenting with distinct inflammatory reactions in the muscle tissue and often causing myalgia. Muscle atrophy, the latter presenting with marked muscle weakness, often with clear muscle atrophy and mesenchymal abnormalities in the biopsy. Ultrasound well documents muscle atrophy, sometimes compensatory hypertrophy, as well as mesenchymal abnormalities such as lipomatosis and fibrosis. In very acute myositis, as in pyomyositis muscle edema and abscesses can be depicted. Typical findings in autoimmune mediated myositis are reported based on our own experiences in 75 patients and according to the literature. The degree and distribution of muscle atrophy and mesenchymal abnormalities visualized by ultrasound can give clues to the type and prognosis regarding muscle function. Additionally, ultrasound can be used for searching the optimal biopsy site. PMID- 8517072 TI - [Primary diagnosis of bone tumor by sonography]. AB - On a 23-year-old patient with an unclear clinical picture the sonographic examination of bone and soft tissue enabled an early detection of a pathological process, thus helping to direct the further use of radiological diagnostics. Unfortunately, the patient could not be helped due to the rapid onset of the diseases. But the case underscores the useful intervention of sonographic examination in the diagnosis of tumors located in locomotor system. PMID- 8517073 TI - [Use of an improved transmission ultrasound camera for diagnosis of rheumatic joint diseases]. AB - Transmission (TM) sonography allows a reliable and fast imaging of soft tissues like joint capsules and tendons, especially of hands and feet. Bony structures appear blurred, but serve as landmarks for easy orientation on the ultrasonic images. The quality of imaging allows a reproducible measurement of joint capsule parameters. Inflammatory alterations of joints are recognized earlier than with conventional x-rays. TM sonography contributes to the diagnostic panel for rheumatic diseases, which involve soft tissues and joints of hands and feet. Today, TM sonography cannot compete with conventional reflex sonography in general arthrosonography, but it is an interesting addition. Follow-up studies will show whether objective joint parameters available by TM sonography may help to both indicate disease progression and to monitor therapeutic interventions in rheumatic diseases. PMID- 8517074 TI - [Ultrasonic diagnosis of inflammatory rheumatic diseases]. AB - During the last two decades, sonography has become more and more important in the diagnosis of rheumatic diseases. With the development of high-frequency realtime transducers, detailed images of the musculoskeletal system can be provided. Furthermore, sonography or echocardiography is able to detect systemic manifestations of connective tissue diseases. Compared to plain films, which mainly evaluate bony lesions of inflammatory joint diseases, sonography is used to assess non-bony abnormalities (synovial membrane, cartilage, menisci, tendons) and synovial space. Pannus and effusion as indicators of inflammatory rheumatic disease can easily be examined by sonography. However, sonographic findings in rheumatic diseases are mostly nonspecific and can rarely be used to distinguish between different diagnoses, which is sometimes possible using plain x-rays (i.e., pencil-in-cup). Sonography has proven to be a meaningful diagnostic tool in evaluating tumors in subcutaneous tissue or muscles. The diagnostic results of musculoskeletal sonography are today compared to those obtained by computed tomography (CT) and magnetic resonance imaging (MRI). Although musculoskeletal MRI can visualize bony and non-bony structures at the same time, sonography is still of particular interest in the diagnosis of rheumatic diseases, because it is a noninvasive, widely available, relatively inexpensive imaging modality which can be rapidly performed and repeated. PMID- 8517075 TI - [Value of arthrosonography of the shoulder in rheumatologic diagnosis. Examination technique, findings and their interpretation]. AB - The sonographic examination of the shoulder has established itself in the diagnostic spectrum of the imaging methods. Especially the results of the rotator cuff have contributed to the fact, that arthrosonography is now indisputable for the shoulder examination. In this paper another scan--the examination through the fossa axillaris--is added to the standard ones, to find the early changes of the shoulder capsule in order to receive efficient results in discovering the omarthritis. PMID- 8517076 TI - [Ultrasound diagnosis of joints and tendons in the body periphery in inflammatory rheumatic diseases]. AB - Possibilities and limits of ultrasound-presentation of the tendons and of the joints in the periphery of the body are shown by way of examples of normal and pathological conditions in the area of the hand and the foot. The margin of erroneous analysis, particularly in the field of ultrasound-diagnostics, of damages of the tendon itself are discussed in detail The article concludes with a critical assessment of the clinical relevance concerning the therapeutic consequences. PMID- 8517077 TI - [Reconstruction of the breast with the m. latissimus dorsi flap after previous mastectomy]. AB - The application of this method over 11 years has shown that careful preoperative planning is crucial for the achievement of good results. There is, however, no restitutio ad integrum. The reconstructed breast will always have a rather firm structure and tend to be scarred. However, the risk of necrosis is reduced by the good vascular and nervous supply which also provides optimal conditions for mamilla reconstruction. Intra- and postoperative antibiotic treatment lowers the risk of infection. PMID- 8517078 TI - [Drug therapy of urge incontinence in the female]. AB - In this study we urodynamically examined 105 women suffering from urge incontinence before and 4 weeks after treatment with various drugs. The subjective and objective findings in the 3 patients' groups are compared. The results showed that the patients treated by spasmolytics (Oxyphenonium bromatum/Hexasonium jodatum/Papaverin) had the lowest rate of side effects in comparison with the women treated by calcium channel blockers and spasmolytics (Diltiazem/Oxyphenonium bromatum) and those with imipramine therapy. But the success rate of the first group was the lowest, too. PMID- 8517079 TI - [The development of pelviscopic (laparoscopic) surgical procedures in former East Germany--statistics from 1986-1988 inclusive]. AB - The fourth German pelviscopy/laparoscopy statistical report includes survey data on a total of 219,314 laparoscopies from 354 clinics and 40,892 laparoscopies from 161 private practices. Clinics' response rate was 44.7%, 98.9% of them reported performing laparoscopies; and the number of serious complications requiring laparotomy or control laparoscopy was 492 (2.2/1,000). For private practices, the comparable figures were 66%, 90.8% and 123 (3/1,000), respectively. Compared with data from the third laparoscopy statistical survey, the data show a slight increase in serious complications, most of which were mechanical lesions of blood vessels in the abdominal wall or in the mesosalpinx, followed by mechanical lesions of the intestine. As shown by the previous survey, 16.5% of the complications were burns. For tubal sterilization, bipolar techniques were still predominant; approximately equal numbers of departments used this method, with or without subsequent transsection of the tubes. Endocoagulation by the method of Semm was the second most popular procedure; the use of clips and rings was of little significance. Monopolar high-frequency (HF) current was still used with transsection by 4.1% of clinics (4.7% of private practices) and without transsection by 2.5% (5.3%). Sterilization failure rates remained the same as those previously reported (2.5/1,000 in clinics, 2.8/1,000 in private practices), the highest rates were observed after the use of monopolar HF techniques. Sixty-six percent of the clinics and 41% of the private practices reported their intention to increase the use of endoscopic operational methods. PMID- 8517080 TI - [Effect of intracavitary irradiation on the venous system of the pelvis and leg]. AB - A late complication of combined radiotherapy for malignoma of the inner genital tract is leg edema, whether of venous or lymphatic origin, which is not always clear. To analyse the influence of radiotherapy upon the pelvic and leg venous system, we performed sonographic caliber, occlusion plethysmographic and light reflexion rheographic measurements of veins in 32 patients prior and subsequent to irradiation. No statistically significant difference was found between mean values measured with the different methods. A clear deterioration of venous function was detected after treatment. Sonographic examinations of pelvic vessels after radiotherapy showed veins much less clearly outlined and with thicker walls, thus pointing to a direct connection between irradiation and edema of the vein wall. Whereas deterioration of the other parameters may also be explained by, for example, long periods of lying. Since according to our own observations, an insufficiency of the leg venous valves occurs relatively often, sometimes even years later, there is a clear correlation between irradiation and edema of the venous wall, with a slight deterioration of venous function detectable directly after irradiation. In order to prevent vein damage, prophylaxis of thrombosis and vessel topography should therefore always be considered when planning radiotherapy. PMID- 8517081 TI - [Cytogenetics of unfertilized or undivided oocytes within the scope of in vitro fertilization: relation to the kind of hormonal stimulation]. AB - A cytogenetic analysis could be performed on 343 out of 566 oocytes which remained unfertilized or uncleaved during our in vitro fertilization (IVF) programme. The results were analyzed in relation to the kind of ovarian stimulation by classification of the patients into two groups: treatment with human menopausal gonadotropin (hMG) or treatment with clomiphene citrate (CC). There was no significant difference for the total rates of abnormal oocytes (hMG: 28.6%, CC: 32.2%), the rates of aneuploidy (hMG: 14.4%, CC: 16.9%), and the rates of hyperhaploidy (hMG: 3.9%, CC: 8.5%). These results suggest that the kind of medication for induction of multiple follicular growth does not influence the rate of cytogenetic anomalies in human oocytes. PMID- 8517082 TI - [What is the predictive value of ultrasound diagnosis in suspected extra-uterine pregnancy in routine clinical practice?]. AB - In this retrospective study the data of 340 patients who underwent invasive diagnostics in suspected ectopic pregnancy from 1985 to 1991 are being analyzed. The aim of this study is to examine the prognostic value of ultrasonic findings after the introduction of transvaginal sonography and highly sensitive urine pregnancy tests in the every day clinical routine. In transvaginal ultrasound significantly more direct signs of an ectopic pregnancy than in the abdominal technique were found showing a markedly higher positive predictive value: 93.5% for an extrauterine double ring, 90.7% for inhomogeneous adnexal masses with the simultaneous finding of echogenic fluid in the pouch of Douglas and 79.3% for isolated inhomogeneous adnexal masses. The predictive values for indirect sonographic hints of suspected extrauterine gravidity were 78.4% for an empty uterine cavity and 87.3% for echogenic fluid in the pouch of Douglas. With growing experience in the vaginal ultrasound technique the positive predictive values of all these signs reached 91% to 98%. Additionally the rate of false negative urine pregnancy tests in patients with ectopic pregnancy sank with increasing sensitivity from 49% (1000 IU HCG/l) to 3.2% (50 IU/l). Summarizing all these factors the reliability of conservative diagnostic means in suspected ectopic pregnancy raised considerably from 56.4% to 94.3% during the course of our study. PMID- 8517083 TI - [Clinical aspects of amniotic fluid embolism]. AB - At the Clinic Obstetrics and Gynecology, Allgemeines Krankenhaus Celle, two cases of amniotic fluid embolism were observed. The first case showed the two characteristic phases of the disease (cardiopulmonary shock followed by severe disseminated intravascular coagulopathy). During the onset of the cardiorespiratory symptoms, the patient underwent cesarean section and a healthy infant was born. The mother survived. The other patient died of cardiopulmonary arrest. Cesarean section was carried out immediately. At first, the infant was heavily depressed, but further development was normal. Inspite of great advances in intensive care amniotic fluid embolism still is considered to be a very dangerous event with 86% maternal mortality. PMID- 8517084 TI - [Ileus in pregnancy induced by a gastric balloon]. AB - Complications during a pregnancy caused by a gastric balloon as a weight reduction device are presented. We refer about a patient in the 35th week of pregnancy who suffered with abdominal cramping. She was studied for hours before the decision for a laparotomy and cesarean section was made. Just before starting, a gastric balloon which was implanted in the early pregnancy for loss of body weight was expelled and the patient was healthy. PMID- 8517085 TI - [Our gynecologic heritage. 100 years ago in the Zentralblatt]. PMID- 8517086 TI - Effectiveness of screening on breast cancer in the city of Utrecht the DOM project. PMID- 8517087 TI - Some genetic aspects of breast cancer. PMID- 8517088 TI - Quality of life in breast cancer--results from 3 cancer research campaign studies. PMID- 8517089 TI - Western life style and breast cancer risk. PMID- 8517090 TI - Psychosocial rehabilitation: a new challenge for oncology. PMID- 8517091 TI - The problems of imaging and interpretation of the treated breast. PMID- 8517092 TI - Routine follow-up of patients following primary therapy for early breast cancer: what is useful? PMID- 8517093 TI - Imaging of osseous metastases. PMID- 8517094 TI - Lymphoedema following breast cancer treatment. PMID- 8517095 TI - Sexual life and pregnancy before and after breast cancer. PMID- 8517096 TI - Doubts on the future cost-effectiveness and desirability of population-based breast screening in The Netherlands. PMID- 8517097 TI - Drug interactions with inhalational anaesthetics. AB - The literature concerning the interactions between volatile anaesthetics, nitrous oxide and other compounds is reviewed. The majority are well known and most can be managed by careful dosage of the anaesthetics. The following interactions should be stressed since these are less predictable or potentially fatal. Of the cardiovascular drugs mainly the Ca++ channel blockers require attention. The volatile anaesthetics act synergistically with these drugs on the inhibition of cardiac conduction and may induce cardiac arrest. Aminoglycoside therapy should prompt an alternative to enflurane because of increased nephrotoxicity with this combination. Thiopentone induction makes the dog heart more susceptible to arrhythmias, especially during anaesthesia with volatile anaesthetics. Probably pentobarbitone, etomidate or a benzodiazepine should be preferred as an alternative to thiopentone when the use of adrenergic drugs peroperatively is anticipated. Nitrous oxide augments the sequelae after coronary air emboli and impaired cerebral perfusion in animals. The necessity of this drug should therefore be considered when anaesthetizing patients undergoing open heart surgery and patients with severe carotid or cerebral arteriosclerosis. PMID- 8517098 TI - Redistribution of lymphocytes after major surgical stress. AB - Major surgery evokes an endocrine stress response, characterized by increased serum cortisol, plasma adrenaline and noradrenaline. Furthermore, surgical stress is accompanied by lymphopenia and granulocytosis in peripheral blood. The changes in peripheral white blood cells have been demonstrated after surgery as well as after cortisol infusion. The aim of the present study was to investigate to which tissues/organs peripheral blood lymphocytes are redistributed after major surgery. From 20 rabbits lymphocytes were isolated from peripheral blood, labelled with indium-111-tropolene and reinjected intravenously into the rabbits. Ten of the rabbits underwent major surgery (upper laparatomy) during general anaesthesia, while the control group (n = 10) was anaesthetized without surgery. The endocrine stress response to surgery was measured as serum cortisol, plasma adrenaline and noradrenaline. The redistribution of lymphocytes was imaged with a gamma camera and calculated with a connected computer before, 2, 4, and 7 h after the skin incision. Compared to preoperative values, laparotomy resulted in an increase in serum cortisol from 116.6 to 461.9 nmol/l (mean) and a decrease in the fraction/percentage of lymphocytes in peripheral blood from 43.8% to 14.7% 7 h after surgery. Simultaneously, the activity of the heart and lungs together decreased to 76.1% of initial values, while the spleen activity was unaffected. The radioactivity of the lymphatic tissue increased to 137.8% and 134.7%, respectively, 4 and 7 h after the start of surgery. The results indicate that major surgery induces a redistribution of lymphocytes from peripheral blood to lymphatic tissue. It is suggested that the endocrine stress response may be of major importance. PMID- 8517099 TI - Beclomethasone prevents postoperative sore throat. AB - The effects of a dose of beclomethasone inhaler (50 micrograms) or lidocaine 10% spray on postoperative sore throat were studied in 120 patients undergoing tracheal intubation for elective surgical procedures. Fifty-four patients (90%) in the beclomethasone group scored no postoperative sore throat compared with 27 (45%) in the lidocaine group (P < 0.001). Beclomethasone inhaler seems to be highly effective in the prevention of postoperative sore throat and is therefore to be recommended before tracheal intubation for general anaesthesia. PMID- 8517100 TI - Diaphragmatic activity during isoflurane anaesthesia in dogs. AB - The effect of isoflurane administration on diaphragmatic activity was investigated in six anaesthetized mechanically ventilated dogs. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during supramaximal stimulation of both cervical phrenic nerves at frequencies of 0.5, 10, 20, 50 and 100 Hz under partially isometric conditions at 1, 1.5 and 2 minimum alveolar anaesthetic concentrations (MAC), after maintaining 1 h of stable conditions. Pdi measurements were made at the start of the stimulation (initial) and at the end of a 2-s period (2-s). The force-frequency relationship was compared at each anaesthetic level. For single twitch (0.5 Hz) stimulation, the time constant of diaphragmatic relaxation was also assessed. The sequence of changing anaesthetic depth was altered in random fashion between animals. Pdi amplitude at single twitch stimulation was unchanged at the three anaesthetic concentrations. There was no significant difference in initial Pdi at various stimulus frequencies with increasing depth of isoflurane anaesthesia. In addition, no change in 2-s Pdi during low frequency stimulation (10 and 20 Hz) was noted during any of the three levels of anaesthesia. By contrast, 2-s Pdi with 50 Hz stimulation during 2 MAC isoflurane exposure decreased significantly below Pdi levels seen at 1 and 1.5 MAC (P < 0.01). Furthermore, 2-s Pdi at 100 Hz stimulation decreased significantly in a dose-dependent fashion. From these results, we conclude that isoflurane reduces diaphragmatic activity at higher stimulation frequencies of 50 and 100 Hz. PMID- 8517101 TI - Reinduction of the hypnotic effects of thiopental with NSAIDs by decreasing thiopental plasma protein binding in humans. AB - The effects of 14 non-steroidal anti-inflammatory drugs (NSAIDs)--naproxen, ibuprofen, mefenamic acid, ketoprofen, indomethacin, fenoprofen, diclofenac sodium, aspirin, salicylic acid, piroxicam, sulindac, fenbufen, flurbiprofen and benzydamine, on the plasma protein binding of thiopental and the clinical consequences of such interactions were studied. Four of them, naproxen, ibuprofen, salicylic acid and aspirin, very significantly decreased the protein binding of thiopental in vitro in human plasma (P < 0.005). Structurally, they were salicylates and propionic acid derivatives among the six classes of NSAIDs studied. The aspirin study demonstrated that the protein-displacing phenomenon was temperature-dependent, and concentration-dependent. Clinically, aspirin administered intravenously resulted in a significant increase in the percentage of plasma free thiopental from 16.01 +/- 3.59% to 22.27 +/- 3.96% (P < 0.001, n = 10) in patients undergoing surgery, and resulted in three of seven patients sleeping again during recovery from thiopental-induced anesthesia. Although the effect of chronic use of NSAIDs before anesthesia is uncertain, studies should be carried out to find out if naproxen, ibuprofen, and aspirin influence the depth of anesthesia, time of recovery and duration of action of thiopental. PMID- 8517102 TI - Isoflurane inhibits muscle fasciculations caused by succinylcholine in children. AB - The incidence and intensity of muscle fasciculations as well as the occurrence of cardiac arrhythmias following succinylcholine were evaluated in 36 premedicated children (1.0-5.7 years) after intravenous induction with thiopentone or after inhalation induction with isoflurane (3.75 vol-% in 70% nitrous oxide in oxygen). The study was randomized. In the thiopentone group, fasciculations were seen in all children and in the isoflurane group in 5 of 18 children (P < 0.001). The median of the duration of fasciculations was 15 s with a minimum of 5 s and maximum of 36 s (1st quartile 9 s and 3rd quartile 20 s) in the thiopentone group and 0 (0-15) s with a 1st quartile of 0 and a 3rd quartile of 3 s in the isoflurane group (P < 0.001). No cardiac arrhythmias were noted in either group. In conclusion, isoflurane in nitrous oxide inhibits succinylcholine-induced muscle fasciculations in children. PMID- 8517103 TI - Platelets in shed mediastinal blood used for postoperative autotransfusion. AB - Ten patients undergoing open-heart surgery received postoperative autotransfusion of shed mediastinal blood collected in the cardiotomy reservoir. The number, function and morphology of the platelets found in the shed blood were investigated. Platelets were counted using an electronic counter compared with light microscopy. Morphology of platelets was studied with electron microscopy. Platelet aggregation was studied using an aggregometer. Dense granule secretion was measured as the extracellular appearance of adenosine triphosphate. Enumeration of platelets in shed blood using the two methods gave different results. Thus, the electronic counter gave a mean platelet count of 62 x 10(9).l 1, while light microscopy revealed only a mean platelet count of 10 x 10(9).l-1. Electron microscopy disclosed few platelets, but numerous cytoplasmatic fragments smaller than or up to the same size as platelets. The platelets found were mostly shape-changed, spheroid, characterized by centralization and loss of alpha granules and dense bodies, all changes that indicated irreversible platelet activation. The platelets failed to aggregate in response to the presence of thrombin, adenosine diphosphate or collagen, and secretion of adenosine triphosphate was absent. Plasma from the shed blood was not capable of inducing spontaneous aggregation in platelet-rich plasma from healthy donors. These results indicate that infusion of larger volumes of autotransfused blood should be supplemented with platelet concentrates. PMID- 8517104 TI - Direct vascular effect of ropivacaine in femoral artery and vein of the dog. AB - A study was conducted to examine the direct vascular effect of ropivacaine, in comparison with the effect of bupivacaine and lidocaine. Changes in tension induced by ropivacaine (10(-5)-3 x 10(-3) mol l-1) and lidocaine (10(-5)-10(-2) mol l-1) were examined cumulatively in vascular rings of dog femoral artery and vein under basal tension, or in those which had been precontracted with phenylephrine submaximally in Krebs' bicarbonate solution at 37 degrees C aerated with 95% O2 and 5% CO2 (pH 7.4). The change in tension induced by 10(-2) mol l-1 ropivacaine was tested under basal tension in vascular rings bathed in HEPES buffer (pH 6.8). Ropivacaine induced greater constriction than bupivacaine at concentrations over 10(-3) mol l-1 in vascular rings under basal tension (P < 0.01). The maximal contraction was induced by ropivacaine at 10(-3) mol l-1, averaging 51.5 +/- 2.8% (n = 11) and 27.0 +/- 3.7% (n = 12) of the maximal contraction induced by epinephrine in the artery and vein, respectively, and the contractions induced by ropivacaine at 10(-2) mol l-1 were 16.3 +/- 2.0% (n = 11) and 5.5 +/- 1.1% (n = 9), respectively. Phenylephrine (10(-6) mol l-1) precontracted artery was contracted significantly by ropivacaine at 3 x 10(-4) mol l-1 and 10(-3) mol l-1, and by bupivacaine at 3 x 10(-4) mol l-1, whereas the phenylephrine (10(-6) mol l-1)-precontracted vein was relaxed by these anesthetics. Lidocaine did not exert constricting effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517105 TI - Blockade of the abdominal muscles measured by EMG during lumbar epidural analgesia with ropivacaine--a double-blind study. AB - A single shot of 20 ml of 1%, 0.75% or 0.5% ropivacaine was administered epidurally (at L2/3 level) to 30 volunteers, in a double-blind manner. The blockade of the rectus abdominis muscle was measured quantitatively by registration of the average rectified electromyographic signal (AREMG) at the T7, T9 and T11 motor segmental levels and with a qualitative test for blockade of the rectus abdominis muscle (the so-called RAM test). The maximal cranial spread of analgesia, evaluated by the pin-prick method, was not significantly different for the three concentrations (T8-T10 dermatome; median value). The intensity of motor blockade, measured by the AREMG method, increased progressively from the T7 segment and caudally with all three concentrations. The blockade was partial (i.e. 85-25% of baseline AREMG activity was present at its maximum) in all subjects. When the effect of the three concentrations of ropivacaine was compared at the same segmental level, the intensity and duration of maximal motor blockade seemed to be dose-dependent, but the difference was not statistically significant. The total duration of motor blockade was shorter with the 0.5% solution than with the higher concentrations. The AREMG method gave a more exact and graded picture of blockade of the rectus abdominis muscle than the RAM test. The duration of sensory blockade did not outlast motor blockade at any level. In half of our subjects the maximal spread of sensory blockade was either equal to or higher than the spread of partial motor block. In the other half, this relationship was reversed--the maximal cranial level of partial motor block was 1 4 segments higher than the maximal level of analgesia. PMID- 8517106 TI - Haemodynamics and fluid balance after intravenous infusion of 1.5% glycine in sheep. AB - With the aim of studying the pathophysiological background of the "TUR syndrome", we gave six conscious ewes an intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min. Isotonic saline infusions served as controls. Central haemodynamics were monitored. The plasma concentrations of protein, K, Na and vasopressin, and plasma osmolality were measured repeatedly for up to 4 h. The urinary excretions of Na, K and osmoles were also followed. Both infusions caused an elevation of the mean arterial pressure. With glycine, the pressure increased from 93 +/- 4 to 112 +/- 12 mmHg (12.4 +/- 0.5 to 14.9 +/- 1.6 kPa) (mean +/- s.d.). The pulmonary capillary wedge pressure increased from 7 +/- 3 to 16 +/- 3 mmHg (0.9 +/- 0.4 to 2.1 +/- 0.4 kPa) and remained slightly elevated. The central venous pressure rose from 2 +/- 3 to 11 +/- 3 mmHg (0.3 +/- 0.4 to 1.5 +/- 0.4 kPa) but returned to baseline within 30 min after the infusion. Infusion of glycine resulted in a decrease in the plasma Na concentration from 144 +/- 3 to 114 +/- 4 mmol/l. The plasma osmolality decreased from 290 +/- 2 to 280 +/- 1 mosmol/l, and remained low. There was a median 6-fold increase in plasma vasopressin concentration, while saline did not elicit vasopressin release. Despite the absence of electrolytes in glycine solution, the urinary excretion of sodium amounted to 106 +/- 40 mmol. We conclude that i.v. infusion of 1.5% glycine solution in sheep causes a transient circulatory strain and natriuresis. Moreover, a vasopressin-mediated reduction of maximal water excretion contributes to persisting hypoosmolality. PMID- 8517107 TI - Effects of hypothermia in hypercapnia and hypercapnic hypoxemia. AB - Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extreme hypercapnia (PaCO2 approximately 20 kPa) at FiO2 0.5, and allotted to a hypothermic group (31.5 +/- 0.1 degrees C, n = 6) or a control group (39.6 +/- 0.2 degrees C, n = 6). Compared with the controls, the hypothermic animals had higher PaO2 (19.2 vs 15.6 kPa, P < 0.05), SaO2 (97.2 vs 89.3%), SvO2 (78.7 vs 68.2%), end-tidal O2 (34.5 vs 24.8 kPa) and arterial pH (7.01 vs 6.91), (P < 0.01), but lower PvO2 (7.0 vs 10.2 kPa) and PaCO2 (13.2 vs 23.5 kPa), (P < 0.01). Hypothermia reduced O2 delivery (DO2), O2 consumption (VO2) and CO2 production by 40-45% (P < 0.05), but O2 extraction ratio, i.e. VO2.DO(2)-1 x 100(%), did not differ between groups. Hypothermic animals had lower heart rate (127 vs 223 beats.min-1, P < 0.05) and cardiac output (2.5 vs 3.9 l.min-1, P < 0.01). Subsequently, the inspired oxygen fraction (FiO2) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30-min intervals. At FiO2 0.3, the hypothermic group had higher PaO2 (10.0 vs 5.7 kPa), SaO2 (91.3 vs 28.5%), PvO2 (5.8 vs 3.4 kPa), SvO2 (70.7 vs 10.3%), end-tidal O2 (16.7 vs 8.5 kPa), O2 delivery (344 vs 155 ml.min-1), arterial pH (7.02 vs 6.94) and systemic vascular resistance (3850 vs 1652 dyn.s.cm-5 (38,500 vs 16,520 microN.s.cm-5)) compared with the controls (P < 0.01), while PaCO2 was lower (12.4 vs 22.7 kPa), as well as O2 extraction ratio (23 vs 63%) and O2 half saturation tension (4.3 vs 8.0 kPa) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517108 TI - Combined effects of adrenergic and intravenous anesthetic agents on inositol monophosphate levels in rat liver prisms. AB - Combined effects of adrenergic and intravenous anesthetic agents on phosphatidylinositol (PI) turnover were studied using rat liver prisms incubated with [3H]myo-inositol. Rat liver prisms responded to epinephrine, norepinephrine and phenylephrine dose-dependently with an increase in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine-induced effects were seen only at concentrations as high as 10(-4) mol.l-1. The enhancement of IP1 formation induced by epinephrine was potentiated by thiamylal at concentrations of 10(-5) mol.l-1 and 10(-4) mol.l-1, remained unaffected by ketamine, fentanyl or midazolam, but was dose-dependently inhibited by droperidol. The present results from in vitro studies of liver cell metabolism suggest that alpha-adrenergic agents in combination with barbiturates may potentiate liver cell damage by activation of PI turnover and interrelated intracellular Ca++ accumulation. PMID- 8517109 TI - Chronic catheterization of the epidural space in rabbits: a model for behavioural and histopathological studies. Examination of meptazinol neurotoxicity. AB - A technique of epidural catheterization in rabbits is described. Twelve albino rabbits received a totally implanted epidural catheter system. The system was implanted surgically, and the functioning of the system tested for a period of 3 months. X-ray examinations following epidural contrast injections showed a distribution up to Th4 following 1.5 ml and Th8-9 following 1.0 and 1.25 ml. Epidural injection of lidocaine throughout the study period proved the system to be functioning for all 3 months. Another 12 rabbits were included for the neurotoxicological examinations following epidural catheterization, without any injections (three rabbits), epidural injections of saline (four rabbits) and meptazinol (five rabbits) once a day for 14 days. Histopathological examinations showed a fibrous cocoon, at the tip of the catheter, in all rabbits. In the group of rabbits which did not receive any injections, the cocoon was slightly infiltrated with leukocytes and local depression of the spinal cord was observed in one rabbit. In the saline-injected group this infiltration was more pronounced and in one rabbit it extended into the meninges. Three rabbits showed local depression of the spinal cord and local myelopathy of the white matter in the area adjacent to the cocoon. In the group of rabbits receiving meptazinol, three out of five had local depression and myelopathy of the white matter. In this group these findings were more pronounced. In two rabbits the myelopathy extended transversely through the white matter into the grey matter of the spinal cord. The number of pathological changes in the group receiving meptazinol was significantly higher compared to the control and placebo groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517110 TI - A simple system of quantitative monitoring of neuromuscular block. PMID- 8517111 TI - Omeprazole in outpatient surgery. PMID- 8517112 TI - An unusual insertion of the palmaris longus muscle. AB - In the course of an anatomical dissection at the School of Medicine, a variant form of the palmaris longus muscle was found on the right side; the fellow muscle of the left side being normal. The palmaris longus concerned was found to arise by fleshy fibers from the common tendon for the flexores antebrachii muscles to be divided into a lateral and a medial tendon. The lateral tendon of the muscle was inserted onto the thenar fascia and the scaphoid bone while the medial tendon was being inserted onto the hypothenar fascia and the triquentral bone. PMID- 8517113 TI - [Development and aging of long bones (the second metacarpal)]. AB - The present paper reviewed studies of the development and aging of the second metacarpal, as an example of the long bone. Bone growth and maturation are related to each other, but keep their individuality. Various hereditary and environmental factors are certainly concerned in the development and aging of long bones, as well as in their relationships. Several topics were picked up for the second metacarpal as follows: pseudo-epiphysis; skeletal maturation; size and density; development and aging; heredity of maturity and growth; relationship of growth and maturation; relative growth; racial, side and sex differences; estimation of age and stature. PMID- 8517114 TI - [The parathyroid gland under normal and experimental conditions]. AB - Since Sandstrom reported the first detailed description of the parathyroid glands of human beings in 1880, and Lever first described the ultrastructure of the parathyroid chief cells of rat in 1957, a large number of light and electron microscopic studies have been done on the parathyroid glands of numerous animal species under normal and experimental conditions. This review deals with the comparative morphology of the parathyroid glands in amphibians, reptiles, birds and mammals under normal conditions, and the problem concerning the effects of various experimental conditions on the parathyroid glands in mice, rabbits and hamsters. The parathyroid glands were recognized in all vertebrate animals higher than fish, and arose from the third and fourth branchial pouches. Several animals, such as the newt, lizard, gecko, mouse, rat, hamster and gerbil, had only two parathyroid glands, but most animals had four. In mammals, most of the parathyroid glands were closely associated with the thyroid gland, but in amphibians, reptiles and birds, the glands separated from the thyroid gland. In some mammals, the parenchymal cells of the parathyroid gland were classified under a light microscope into two main types of cells: chief cells and oxyphil cells. Examinations under an electron microscope also showed the chief cells having many cell organelles and the oxyphil cells filled with numerous mitochondria in the parathyroid glands of human beings, monkeys, cows, horses, bats and turtles. In addition, the chief cells in most animals were classified at the light microscopic level into light cells and dark cells, moreover the chief cells were also electron microscopically divided into a light and dark type showing different functional phases of a single cell type when osmium or glutaraldehyde fixative was used. However, it is widely accepted today that differences in cytoplasmic density of the chief cells are due to artifacts produced in the process of tissue preparation. The parenchymal cells of the parathyroid gland of the newt were divided into the basal cells (supporting cells) and the suprabasal cells (chief cells). In the parathyroid gland of the frog and toad, blood vessels and connective tissues were not present. In the parathyroid gland of the rabbit and hamster, the water-clear cell was observed. In the electron microscopic radioautograph of the parathyroid gland treated with 3H-leucine, most of the silver grains were seen over cisternae of the granular endoplasmic reticulum at 15 minutes, over the Golgi complexes at 30 minutes, and over secretory granules at 60 minutes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8517115 TI - Muscle study of the musk shrew (Suncus murinus riukiuanus). I. Gluteal and thigh muscles. AB - The gluteal and thigh muscles of the musk shrew (Suncus murinus riukiuanus) were macroscopically studied. The sartorius was not observed in any of the specimens examined. The gracilis was divided into two bellies. The semitendinosus had two heads of origin, the ischial and vertebral. However, most of the gluteal and thigh muscles of this animal were quite similar with respect to origin, insertion, and also nerve supply to those muscles of rodents and primates, including human beings. All the gluteal and thigh muscles observed in this study were tabulated (see Table 1) and compared with those reported by Sharma (1958) and Isomura (1968). Furthermore, the homology of these muscles to the corresponding muscles of the rodents and of human beings, was discussed in the text (see also Table 1). PMID- 8517116 TI - [Cushion-like structure in coronary arteries of rats]. AB - The vascular architecture in the rat heart was investigated with SEM using a corrosion cast and light microscopy of paraffin sections stained with Hematoxylin Eosin and Elastica-Domagk methods. In corrosion cast models of the left and right descending coronary arteries, Y- and T-type branching patterns were distinguished. The Y-type bifurcations were found at branching sites of the larger vessels and precapillary arterioles in the myocardium, whereas the T-type bifurcations were found at branching sites of the smaller vessels. On the surface of the corrosion cast of the T-type bifurcation symmetrical shallow depressions were observed at an orifice of a daughter vessel. The depression was confirmed to be produced by protrusions consisting of smooth muscles and elastic fibers of the vascular wall. The structure is presumed to be an arterial cushion which plays some role in avoiding plasm skimming and regulating blood flow. PMID- 8517117 TI - [Aggregations of macrophages in the digestive tract of several mammals and their functional significance]. AB - Our previous finding in the guinea pig that macrophages are aggregated at the villus tips of the small intestine and phagocytose effete enterocytes, in contrast to the accepted view that the enterocytes are exfoliated into the lumen, was extended in the present study to the large intestine of this animal and to the intestines of other mammals. In the large intestine of guinea pigs, aggregations of macrophages with an acid phosphatase activity were found beneath the epithelial lining, linearly surrounding the crypts. The macrophages contained debris of epithelial cells in their phagosomes, suggesting that the macrophages phagocytose apoptotic epithelial cells. This finding was supported by tracing BrdU-marked enterocytes, which were found to be taken up by the macrophages in the lamina propria. The macrophage aggregation was also recognized in the ileum of newborn guinea pigs, a finding favoring the idea that it represents a constant and intrinsic phenomenon and is not induced by penetration of foreign particles or other immunological events. In the monkey small intestine, macrophages with abundant phagosomes aggregated in large numbers in the lamina propria of the villus tips and were found to phagocytose enterocytes. In the hamster and rat, macrophages were numerous in the villi of the small intestine but they did not reveal images suggesting their involvement in the enterocyte removal. The mouse and rabbit showed only few macrophages with an acid phosphatase activity in the lamina propria of villi. The present finding in the monkey urges an investigation as to whether the novel mechanism of enterocyte disposition by subepithelial macrophages might be taking place in the human intestine. PMID- 8517118 TI - Morphologic and quantitative study of the efferent vestibular system in the chinchilla: 3-D reconstruction. AB - An HRP study of the EVN has been performed. Three groups of somas have been identified: Those located in the proximity of the vestibular nuclei, those sandwiched between the facial genu and the IVth ventricle, and those in the RF, surrounding the abducens nucleus. The number of somas is greater in the contralateral brain-stem side. Axons could be followed through the midline, but could not be traced to a labelled soma. A 3-D reconstruction of the EVN within the brain stem is presented. PMID- 8517119 TI - Polyamines in the lateral vestibular nuclei of the squirrel monkey and their potential role in vestibular compensation. AB - Polyamine synthesis increases in response to injurious stimuli including axotomy and denervation. Reduced eye nystagmus and head-deviation have been observed in unilateral labyrinthectomized (UL) guinea pigs treated with an inhibitor of polyamine synthesis, alpha-difluoromethylornithine (DFMO). We quantified polyamines in the lateral vestibular nuclei (LVN) of control and UL squirrel monkeys during the phase of vestibular compensation (VC) and performed an experiment to determine if DFMO reduces nystagmus previously observed in the guinea pig. Polyamines were detected in the LVN of control and UL squirrel monkeys. Putrescine and spermidine increased in the ipsilateral LVN 3 days after UL with no change in the contralateral LVN. No left-right differences were noted in the 5-day post-UL monkey. DFMO reduced nystagmus in a UL squirrel monkey. These findings suggest that polyamines are important in vestibular function and may contribute to nystagmus observed in VC. PMID- 8517120 TI - Gravity load related asymmetries in the sagittal vestibulo-collic reflex. AB - EMG recordings of the neck muscles (biventer cervicis, complexus, splenius, longus capitis) of decerebrate cats were obtained during pitch and roll stimulations (sinusoidal stimulation: 30 degrees p-p amplitude, 0.2 Hz frequency). Most of the EMG responses to pitch showed activation peaks leading the position stimuli by 56 degrees and inhibition peaks leading by 11 degrees. Conversely, in response to roll the activation peak led by 16 degrees and the inhibition peak by 10 degrees. The activation peaks of the pitch responses were, thus, more asymmetric and more leading than those of the roll responses. Consequently, the harmonic distortion coefficient was significantly higher in pitch than in roll. Moreover, when the vertical semicircular canals were activated in absence of otolithic modulation, the pitch and roll responses maintained the same difference in timing observed in the presence of otolithic coactivation. It appeared that the simultaneous stimulation of both anterior semicircular canals (pitch) induces a greater lead than that of combined anterior and posterior canals (roll). Thus the timing of neck muscle responses to vestibular stimulation depends on the pair of activated vertical semicircular canals. PMID- 8517121 TI - Randomized perturbed posturography: methodology and effects of midazolam sedation. AB - To study quiescent stance without applying external disturbances is not a theoretically appealing way to unveil the dynamic properties of human equilibrium. Methods to disturb equilibrium range from standing on foam surface, attaching vibrators to the calves to interfere with somatosensation, and exposure to body-position tracking environments, as in dynamic posturography (EquiTest). The EquiTest apparatus was modified by a menu-driven software to allow arbitrary movements of the support surface and visual surround, and force data were recorded for subsequent analysis. The support surface was randomly moved in the antero-posterior direction. First equilibrium was studied on the stable support surface, then low (RMS 1.3 cm) and high (RMS 2.6 cm) amplitude movements were used. Vision was either present or absent at all test amplitudes. Equilibrium was evaluated by the confidence (61%) ellipse sway area and average sway velocity during 45 s. Eleven healthy subjects aged 23-36 years (mean 29) were sedated with a short acting sedative, midazolam 0.1 mg/kg. Randomized perturbed posturography was conducted at baseline, and at about 60, 120 and 180 min after injection. Psychomotor tests were conducted at baseline, and at 30, 90, 150 and 210 min. Large interindividual variations were found. One subject could not be tested at all at 60 min due to sleepiness, whereas some subjects felt nearly full awake at 30 min. Sway areas were larger at 60 min, but not subsequently. At 60 min, sway velocities with open eyes were higher, just as when vision was absent and low amplitude movements were used. Later no effects could be shown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517122 TI - Effects of increased inertial load in dynamic and randomized perturbed posturography. AB - Muscular weakness is present in many diseases. The present study attempted to model a relative weakness of postural control muscles by loading the subjects with extra weight, and the effects on EquiTest dynamic posturography and randomized perturbed posturography were assessed. Ten healthy subjects aged 15-39 years (mean 26 years) were used. Their weights ranged 53-82 kg. Equilibrium was measured with and without an extra 20% of body weight attached to the upper part of the trunk by means of pieces of lead metal placed in a specially sewn shirt. Dynamic posturography (EquiTest) comprises a sensory organization test in which the support surface and visual surround are either stable or referenced to the patient's sway, his or her eyes open or closed. In a movement coordination part the platform makes active movements. Antero-posterior sway on a stable support surface with absent or distorted visual cues was marred, and the correction pattern was altered on a movable support surface when the vision was absent. Furthermore, the EquiTest apparatus was driven by special software to produce randomized antero-posterior movements during 45 s. In addition to stable conditions, small and large amplitude perturbations were used. The subject's ability to remain in equilibrium was estimated by the sway velocity and a confidence ellipse sway area during 45 s. During weightbearing, sway areas were larger on the stable support surface both with and without vision. Postural sway velocity was lower when vision was absent both using small and large amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517123 TI - Factors contributing to labyrinthine ataxia. AB - Twenty-one normal adults were the subjects of this study. They were instructed to step in the same position with eyes closed for a total of 50 steps under two conditions: i) Immediately after simultaneous irrigation of the right and left auditory canals for 10 s with 30 degrees C water and 44 degrees C water, respectively, and ii) following irrigation of the right auditory canal with 30 degrees C water. The two conditions simulate two different types of imbalance of labyrinthine function: The former physiological and the latter non-physiological. Under the first condition, 33% of the subjects tended to fall to the right side during stepping. Under the second conditions, 86% showed ataxia. The difference was statistically highly significant, p < 0.01. The results indicate that physiological imbalance does not always cause ataxia. A physiological imbalance occurs during active turning. The motion brings about an ampullopetal lymphatic flow in the ipsilateral horizontal semicircular canal and an ampullofugal flow in the contralateral canal, as under the second condition. The former increases the function of the labyrinth, while the latter decreases it. This results in imbalance but no ataxia. PMID- 8517124 TI - Slow blood flow of the vertebrobasilar system in patients with dizziness and vertigo. AB - We evaluated 102 patients with dizziness or vertigo who were 50 years of age and over, using magnetic resonance imaging (MRI). Slow blood flow (SBF) in the vertebrobasilar system was detected in 36 patients (35%). The patients with SBF experienced dizziness or vertigo for a longer period than those without SBF. The apogeotrophic type of direction-changing nystagmus was observed in 10 of 36 patients with SBF. No significant differences were found between patients with and without SBF with other neurotological tests. Because MRI can detect both infarcts in the hind-brain and SBF in the vertebral and basilar arteries it is recommended for evaluation of vascular disorders in older patients with vestibular symptoms. PMID- 8517125 TI - Vestibular function in cochlear implant patients. AB - Thirty-five patients receiving a cochlear implant were evaluated using vestibular function tests. Twenty-five patients received an intracochlear implant (Nucleus). Three out of 6 patients with normo- or hyporeflexia before implantation showed postoperative vestibular damage. In one case this was iatrogenic. Together with available data from the literature the risk of losing preoperative vestibular function is estimated to be around 60%. Improvement of implantation techniques can probably reduce this risk considerably. PMID- 8517126 TI - Frequency selectivity of central auditory neurons without inner ear. AB - A group of neurons in the inferior colliculus (IC) of the chicken displayed frequency selectivity after surgical removal of both cochleae. Characteristic neuronal frequencies were evident in the following three measures. i) The cells fired spontaneously with discrete preferred interspike intervals; ii) Impulse responses of these neurons to electrical stimuli of cochlear nerves displayed oscillations at the preferred frequencies; iii) When the cochlear nerves were stimulated with a random pulse sequence, a reverse correlation analysis showed that the cells preferred the same frequencies in the stimulus input. Preferred frequencies observed thus far covered over 4 octaves of the auditory range. These "oscillating cells" were found only in a small rostromedial area in the IC. Neuronal frequency selectivity may serve a temporal analysis of sound and underlie sound identification with certain cochlear implants. It may also support interaural crosscorrelation necessary for directional hearing. PMID- 8517127 TI - Functional maturation of cochlear active mechanisms and of the medial olivocochlear system in humans. AB - The aim of this study was to investigate the functional development of cochlear active mechanisms and of the medial efferent olivocochlear system. Otoacoustic emissions (evoked and spontaneous) were recorded in 42 preterm neonates (conceptional age ranging form 33 to 39 weeks) and a control group of 20 young normal-hearing adults. Medial olivocochlear system activity was examined by coupling evoked otoacoustic emission recording to a contralateral stimulation. Otoacoustic emission recordings were carried out using the Otodynamic ILO88 software and hardware. The stimuli were unfiltered clicks and the contralateral stimulation was broad band noise of 50 and 70 dBSPL delivered by an Adam generator. The results revealed the presence of EOAEs and SOAEs from at least 33 weeks in humans, suggesting that the functional maturation of the outer hair cells is nearly complete at that age. The study further revealed that the contralateral stimulation had no effect on evoked otoacoustic emissions in preterm neonates. The lack of activity observed in medial olivocochlear system indicated functional immaturity here, at least before full-term birth. PMID- 8517128 TI - Computational waveform analysis and classification of auditory brainstem evoked potentials. AB - The widely used quantitative descriptors of amplitude and latency of evoked potentials, for peaks and troughs along the waveform, relate to only a limited number of points along the waveform, ignoring the interposed data. Moreover, these descriptors are typically determined manually, rendering them susceptible to user bias. We propose and demonstrate a machine-scoring algorithm for the identification and measurement of Auditory Brainstem Evoked Potentials (ABEP) peaks I, III and V. We further introduce an algorithm for the quantitative analysis of ABEP by waveform, and for clustering records according to waveform characteristics. The results of computerized peak identification and measurement, without user intervention, were correlated with manual measurements of the same peaks in a large number of waveforms. The waveform analysis and classification procedure differentiated waveforms to monaural left, monaural right and binaural stimulation, as well as according to the recording montage. These results underscore the advantages of using information in the waveform of ABEP, which has so far been overlooked. The automated algorithms for evaluation of ABEP by waveform hold the promise of a more comprehensive and consistent evaluation, and hence improved sensitivity. PMID- 8517129 TI - Medial olivo-cochlear system and tinnitus. AB - A possible role of the efferent system in the mechanisms of tinnitus generation has been put forward by several authors. A simple method for studying the functioning of this system is to compare the amplitudes of otoemissions with and without mild contralateral stimulation. In a recent communication, Veuillet et al. (1991) reported that, on the side of tinnitus, the efferent system of patients suffering from unilateral tinnitus seems to be less efficient than on the other side. The results presented here correspond to those obtained in the very first tinnitus patients submitted to a research protocol exploring systematically the efferent system. When possible, the effectiveness was tested in two ways: globally, using evoked otoacoustic emissions (EOAEs) and, very precisely in the frequency zone of the tinnitus, using cubic distortion product 2f1-f2. Preliminary results obtained in bilateral and unilateral tinnitus sufferers show that a majority of them exhibits, at least in the proximity of the tinnitus, a lack of effectiveness of the efferent system. In some of them, instead of the suppressive effect, an increasing one was even observed. PMID- 8517130 TI - Intracochlear electrical tinnitus reduction. AB - Several reports have indicated that some cochlear implant patients experience a reduction in their tinnitus while listening to noise or speech. In the present study, two patients reporting bilateral tinnitus were selected from a group of adults with the Nucleus cochlear implant. They rated their tinnitus loudness and severity and completed the Tinnitus Handicap Questionnaire. The stimuli for electrical stimulation were charge-balanced pulse trains of various repetition rates (frequencies) and inter-electrode distances. A range of electrodes was chosen in each subject, including basal, medial and apical electrodes. For each condition, the hearing threshold level and the uncomfortable loudness level were determined. A range of stimulus levels between these two values were presented randomly. After each presentation, the patients rated the stimulus loudness and the tinnitus loudness on a 0 to 100 scale. These judgements were used to carefully determine the psychometric function between stimulus level and stimulus loudness, and between stimulus level and tinnitus loudness. All the parameters explored were important for maximizing the relationship between tinnitus reduction and stimulus loudness. First, the effectiveness of electrical stimulation in tinnitus reduction depended on the place along the cochlear partition. Second, a pulse rate of 125 Hz showed the greatest efficiency in terms of the current level needed to suppress tinnitus. Third, these two subjects showed rather poor performances in speech perception when using their speech processor in the usual condition and the hypothesis of an influence from tinnitus annoyance is suggested in addition to some more classical predicting factors of speech recognition in cochlear implant users. PMID- 8517131 TI - Neonatal cochlear hearing loss results in developmental abnormalities of the central auditory pathways. AB - We have used animal models of long term neonatal cochlear hearing loss to study developmental plasticity of the central auditory pathways. Newborn chinchilla pups and feline kittens were treated with the ototoxic drug amikacin, so as to induce basal lesions in the cochlea. At maturity these animals were used in single unit electrophysiological mapping studies, in which the cochleotopic organization of primary auditory cortex (of the cat) and the inferior colliculus of the midbrain (in the chinchilla) were mapped. We have observed, both in the midbrain and auditory cortex, massive reorganization of frequency representation. Most striking were the presence of large monotonic regions (i.e. large areas in which all neurons have similar tuning properties). Cochlear lesions which involve inner hair cells clearly modify the normal development of cochleotopic representation in the midbrain and cortical regions. We suggest that similar abnormal patterns of frequency representation will exist in human subjects with long term neonatal hearing loss. PMID- 8517132 TI - Clinical characteristics and hearing recovery in perilymphatic fistulas of different etiologies. AB - Clinical features and hearing recovery were compared between three types of perilymphatic fistula groups; surgically confirmed (PLF-conf, n = 16), suspected (PLF-susp, n = 24) and traumatic (trauma-PLF, n = 11). Initial average hearing level was best in the PLF-susp group (50.9 dBHL), followed by the trauma-PLF (55.7 dBHL) and PLF-conf (59.7 dBHL) groups, though the difference was not significant (ANOVA, p > 0.05). Of 51 patients, 27 cases were operated on and fistula was confirmed in 19 ears (70.4%). Conservative treatment, including bed rest and medication, was given to all patients. After the treatment, meaningful hearing recovery was obtained only at 1 kHz in the PLF-conf group (paired t-test, p < 0.05). However, significant recovery was seen at all frequency ranges (0.125 8 kHz) in the PLF-susp group (average, 16.8 dB; p < 0.01), while hearing improvement was intermediate for the trauma-PLF group. The initial hearing level and the period until the start of treatment strongly correlated with the final hearing level. Although 27 patients (47%) complained of dizziness, the prognosis for vertigo is excellent as noted by other authors. It was concluded that if conservative treatment is started early for PLF patients with mild hearing loss, hearing recovery can be ensured. PMID- 8517133 TI - The localization of synaptophysin in the organ of Corti of the human as shown by immunoelectron microscopy. AB - Synaptophysin, or p38, a polypeptide of molecular weight 38 kD, is a calcium binding membrane protein found in synaptic vesicles of neurons and smooth surfaced vesicles of neuroendocrine cells. Six human neonatal and infant temporal bones were fixed in paraformaldehyde and glutaraldehyde, decalcified in EDTA and were than immunoreacted for synaptophysin (ICN Biomedicals) using the avidin biotin reaction (ABC kit, Vector Labs). The tissue was then prepared for light microscopic surface preparation, radial sections of 5 microns, and serial section electron microscopy. At a light microscopic level, the inner spiral bundle, tunnel spiral bundle, upper tunnel crossing fibers and the base of outer hair cells were stained. At the base of outer hair cells, the immunoreactivity was seen to decrease from the base to the apex and from the first to third outer hair cells. At an electron microscopic level, immunoreactivity at the base of outer hair cells was limited to vesiculated efferent fibers. The degree of immunoreactivity between adjacent efferent fibers varied significantly. Immunoreactive vesiculated endings were also found in the supranuclear region of outer hair cells. PMID- 8517134 TI - Indirect immunofluorescence in the investigation of rapidly progressive sensorineural hearing loss and Meniere's disease. AB - Being aware of the conservation of antigenicity, we performed indirect immunofluorescence on non fixed non decalcified frozen hamster's cochlea. Once killed, the heads of the hamsters were immediately dipped into liquid nitrogen and then stored at -20 degrees C until cutting. The sections were done at the same temperature, with Tissue-Tek embedding the heads to avoid breaking, using a sharp tungsten knife. The immunofluorescence itself was performed with the sera of the patients which were revealed through donkey fluorescein-conjugated antiserum to human immunoglobulins. For counterstaining, we used Evans blue. Twenty patients with rapidly progressive sensorineural hearing loss (according to the clinical criteria of MacCabe) and 6 with Meniere's disease were tested. Five had a specific fluorescence on the stria vascularis. A correlation with the lymphocyte transformation test on human inner ear antigen has been found (p = 0.055). PMID- 8517135 TI - Morphological features of human Reissner's membrane. AB - Light and electromicroscopic investigations of Reissner's membrane were undertaken on 10 cochleae from 6 patients with normal hearing for their age. The membrane consisted of two layers, an epithelium and a mesothelium separated by a basement membrane. The mesothelium was formed by a single thin layer which was intermittently discontinuous. The melanocytes were localized on the mesothelial side of the basement membrane. Their numbers was 2-4 times greater in the upper half of the basal turn and in the middle turn than elsewhere. The epithelium was much thicker and had more irregular features than the mesothelium. It was composed of two types of epithelial cells, flat and rounded. The flat cells were more regular in shape than the rounded cells and they were mainly distributed in the middle and apical turns. Judging from their structure they were in a resting state. The rounded cells covered a smaller area than the flat ones and had numerous microvilli. They assumed three different shapes, cuboidal, spindle-form and spherical and were arranged in four different patterns, namely bands, strands, whorls and clusters. The rounded cells were the most active according to the composition of the cytoplasm and dominated the cell population in the hook and the lower half of the basal turn where the age-related sensorineural degeneration is most apparent. PMID- 8517137 TI - Is the endolymphatic K secretion electrogenic? AB - The endolymphatic potential is assumed to result from active K transport into the endolymphatic compartment and passive K diffusion in the opposite direction. However, in several in vivo experiments, changes in the endolymphatic potential differed from those in the endolymphatic K concentration. Moreover, in in vitro experiments, a negative endolymphatic potential was observed in the presence of ouabain without K gradient between the two compartments. These observations suggest that the coupling between the K transport and the genesis of the endolymphatic potential is not tight. Several factors may separately influence the endolymphatic potential and the K transport such as the acid-base equilibrium, the integrity of Reissner's membrane, the hormonal status, and the Na transport. PMID- 8517136 TI - Acetylcholine controls the gain of the voltage-to-movement converter in isolated outer hair cells. AB - Sensitivity of the electromotility of isolated guinea pig outer hair cells (OHCs) to acetylcholine (ACh) was examined. OHCs were held in a partitioning microchamber in a position so that their ciliary poles were inserted and their somatic length changes measured. Transcellular square-wave stimuli were delivered to record voltage-to-movement conversion of the cells. ACh was applied to the synaptic poles. The transfer function of electromotility intimated shifts of the membrane potential with concomitant gain changes: gain decreases when the membrane potential is shifted in hyperpolarization direction and gain increases when the membrane potential is shifted in the opposite direction due to application of ACh in 100-500 microM concentration. Clear gain increase of the electromotility in basal turn OHCs to ACh was observed, whereas inconsistent results for apical turn OHCs were found. The latter is probably due to the pharmacological dose of ACh used. This possibility is further supported by results in which ACh abolished the sensitivity of the magnitude response of electromotility to DC depolarizing bias. PMID- 8517138 TI - The site of impulse generation in transcranial magnetic stimulation of the facial nerve. AB - The facial nerve can be stimulated in its intracranial course through transcranial magnetic stimulation (TMS). We studied the site of impulse generation produced by TMS by comparing the latencies of the muscle evoked potentials (MEPs) elicited with TMS and intracranial electrical stimulation (IES) of the facial nerve during neurosurgical posterior fossa procedures. In a series of 25 patients, the mean latency of the TMS elicited MEPs, recorded in the orbicularis oris muscle, was 5.0 ms (SD 0.58). Also IES of the distal part of the facial nerve in the internal acoustic meatus showed a mean latency of 5.0 ms (SD 0.68). Proximal IES in the root entry zone of the facial nerve, and intermediate IES between root entry zone and meatus, produced MEPs with significantly longer latencies compared to TMS and distal IES (p < 0.05). The findings suggest that the TMS induced facial nerve activation, leading to a MEP response, takes place within the internal acoustic meatus. PMID- 8517139 TI - Dynamic measurement of gas composition in the middle ear. I: Technique. AB - The middle ear is a balanced gas pocket which loses and gains gas constantly. This balance depends on the continuous interchange of gases from the atmosphere, through the eustachian tube and the circulating blood by diffusion. The relative contribution of each of these two sources can be determined by measuring the gas composition of the middle ear (ME). Because of the small quantity of gas in the ME, adequate sampling and accurate measurement of its composition are extremely difficult. An on-line system for middle ear gas composition measurements is described. The measuring instrument is mass spectrometer. ME gas samples are withdrawn by diffusion, and therefore are very small. Sampling and measurements are performed in a continuous mode. PMID- 8517140 TI - Dynamic measurement of gas composition in the middle ear. II: Steady state values. AB - On-line measurement of ME gas composition in normal middle ears of 5 anesthetized guinea pigs at an established steady state was performed by mass spectrometry. The mean values for the gas composition of the middle ear were found to be: PN2: 82.4%, PO2: 7.6% and PCO2: 10.0%. This composition is very different from that of atmospheric air, and very similar to the gas composition of mixed venous blood. Our conclusions are that the gas composition is basically controlled by interchange with gases present in the blood and not by introduction of air through the eustachian tube. It is therefore proposed that middle ear gas deficiency is secondary not to eustachian tube input failure but to excess loss of middle ear gas due to enhanced diffusion into the blood. This situation exists especially under inflammatory conditions when there is an enlarged number of blood vessels promoting increased gas diffusion into them. Under ordinary conditions this middle ear gas deficiency will probably cause no significant underpressure because the mastoid pneumatization will act as a pressure buffer. When mastoid pneumatization is lacking, as happens in the otitis media syndrome, a pathological negative pressure will ensue. PMID- 8517141 TI - Prevalence and risk factors of chronic otitis media in Korea: results of a nation wide survey. AB - A nation-wide survey on the prevalence and risk factors of chronic otitis media (COM) in Korea was conducted by means of physical examination by otolaryngologists from July to October, 1991. Total subjects examined were 9,321, who were drawn from 2,899 households residing in 60 different areas throughout the country. The overall prevalence rate of OM was 2.85% whereas that of COM was 2.19%. For the study of risk factors of COM, a case-control analysis was made. The prevalence of chronic OM did not vary by sex, nor by urban-rural difference. However, the risk increased with aging. There was a significant geographic variation by provinces. General risk factors such as crowding, economic activity, childhood home, marital status, maternal or paternal age, body weight, smoking habits, age of first otorrhea, preauricular fistula, canal atresia and cleft anomaly imply an increased risk of COM. Other factors such as residency, education, social class, height, history of breast feeding, microtia, nasal septal deviation, nasal polyposis and nasal allergic symptoms showed little influence on COM. PMID- 8517142 TI - Computer-aided three-dimensional reconstruction and measurement of facial canal dehiscence. AB - Location, shape and dimensions of the dehiscence in the facial canal to the middle ear space were studied in 20 temporal bones obtained from 19 individuals aged 1 day to 72 years at death by using our computer reconstruction and measurement method. The most frequent site of dehiscence was the oval window area (70%), particularly in its posterior half and on the inferior to inferomedial aspect of the canal. The shape of the dehiscence tended to be oval in the oval window area, but rather irregular in the other areas. The dehiscence ranged from 0.4 to 2.64 mm in length, from 0.12 to 1.59 mm in width, and from 0.03 to 1.87 mm2 in surface area. Proximity of these dehiscences to the field of otological surgery is stressed. PMID- 8517143 TI - Normal and abnormal nasal growth after partial submucous resection of the cartilaginous septum. AB - Using the nose of growing rabbits as an experimental model, the effects on nasal growth of various Killian-type partial resections of the cartilaginous septum were studied. Larger resections in young animals caused decreased height and length of the nose in the adult stage. Partial resection of the basal rim of the cartilaginous nasal septum demonstrated no effects on the postnatal growth of the nasal dorsum. This is in agreement with the hypothesis that the growth of the nasal dorsum is mainly the result of expansion of an area of thick cartilage within the nasal septum extending from the sphenoid to the nasal dorsum. PMID- 8517144 TI - Immunological aspects and inflammatory mechanisms of allergic reactions. AB - The tissue changes and symptoms that occur during an allergic reaction in the upper respiratory tract are due to inflammatory reactions. The authors give a survey of the different allergic reactions and discuss the different components of the IgE mediated hypersensitivity which is the most important type of hypersensitivity in the upper airways. The production of IgE, the immunoglobulin of the immediate hypersensitivity reaction, is modulated by T-cells through the activity of cytokines. Antigen presenting cells, including Langerhans cells, play an important role in the sensitisation phase. Mast cells and basophils degranulate as a result of a complex enzymatic pathway, in which phosphatidylinositol plays an important role. The mediators released by these cells include vasoactive substances, chemotactic agents and inflammatory proteases; these mediators and those liberated by secondary recruited cells, such as eosinophils and basophils will be responsible for the early and late symptoms. PMID- 8517145 TI - Mucosal immunity in allergic rhinitis. AB - Secretory IgA (SIgA) is the main agent protecting the mucosal districts against both infectious microorganisms and inert foreign macromolecules. A lack of secretory immunity has previously been described in patients with allergic rhinitis, but it is a controversial finding. The discrepant results of SIgA levels found in allergy may partially be due to methodological problems. Sixty patients with previously demonstrated allergic rhinitis, treated or not with specific desensitization therapy and free from clinical manifestation of rhinitis were studied. Normal volunteers and patients with selective 11S IgA deficit, without allergic pathology, were investigated as controls. The titration of SIgA in nasal secretions, performed by an original immunoisoelectro-focusing method, showed significantly decreased values in allergic patients. An evaluation of the IgE level in nasal secretion was performed by ELISA. Low rates of IgE were also found in the intercritic period. PMID- 8517146 TI - Wrong-way swallowing as a possible cause of bronchitis in patients with gastroesophageal reflux disease. AB - A new theory was tested that swallowing the wrong way is the cause of the strong correlation between bronchial symptoms and gastroesophageal reflux disease (GERD). One hundred and nineteen patients who were operated on for hiatal hernia and GERD were compared with 89 patients treated with the proton pump inhibitor omeprazole concerning bronchial symptoms before and after treatment. Both groups had a frequency of cough of 34% before treatment. Omeprazole did not give any significant relief of cough, whereas patients who were operated on with fundoplication and crural repair showed a highly significant reduction of cough and bronchitis. It is believed that the distal anchoring of the longitudinal esophageal muscle by surgery improves esophageal transit and restores the delicate coordination in the swallowing centre between deglutition, the opening of the upper esophageal sphincter, and the epiglottic closure of the laryngeal entrance. It is concluded that the main reason for chronic bronchitis in patients with GERD is intermittent aspiration due to partial mis-swallowing. PMID- 8517147 TI - Ganglions and ganglionic neurons in the cat's larynx. AB - Localization, projections and role of ganglia and ganglionic neurons in the laryngeal framework were demonstrated in cats. Six to 8 large size ganglia containing 50 to 80 ganglionic neurons per ganglion in the paraglottic space, 4 to 6 small ganglia involving 5 to 25 cells in each ganglion dorsal to the posterior cricoarytenoid muscle, and 1 to 3 small ganglia including 15 to 25 perikarya per ganglion around the inferior laryngeal nerve were observed. Each ganglion showed spindle shaped covering fibrous capsule. Ganglionic neurons totaling 600 to 800 were oval shaped with an average diameter of 25 microns. Projections of the ganglionic neurons to the superior cervical ganglion (SCG) and nodose ganglion (NG) through the ipsilateral internal branch of the superior laryngeal nerve and to periphery were detected. From the dorsal motor nucleus of vagus, SCG and NG, the ganglionic cells received projections ipsilaterally. On immunocytochemistry many vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) neurons, some neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-ir neurons and a few substance P (SP)-ir cells were recognized in ganglions. VIP-, NPY-, TH , SP-, and calcitonin gene-related peptide (CGRP)-ir fibers were also observed in and around vessels and glands. Following denervation, VIP-, NPY- and TH-ir neurons and fibers did not change. These results prove that laryngeal ganglionic neurons have endogenic autonomic, especially cholinergic nature and innervate vessels and glands. PMID- 8517148 TI - Current topics in voice production mechanisms. AB - A brief overview of current research in voice production mechanisms is given. The self-oscillatory behavior of the vocal folds is clarified, along with the identification of preferred tissue modes. Fundamental frequency control is reviewed as a coordinated activity between cricothyroid and thyroarytenoid muscles and lung pressure. Lung pressure is shown to be the primary regulator of vocal intensity. For eventual application to the study of voice disorders, a method of measurement of contact stress on a hemilarynx preparation is described. PMID- 8517149 TI - Muscle misuse voice disorders: description and classification. AB - It is apparent that voice disorders frequently labelled "functional" are associated with laryngeal muscle misuse. This use of the word "functional" is, however, intrinsically ambiguous, and so we propose an alternative term based on descriptive features of dysfunction: "muscle misuse voice disorders". Persistent phonation with an abnormal laryngeal posture can lead to organic changes such as nodules or polyps, particularly in females with posterior glottic chink. We hypothesized that the chink was related to an overall increase in laryngeal muscle tension, and more directly due to inadequate relaxation of the posterior crico-arytenoid muscle during phonation. We employed the term "muscular tension dysphonia" (MTD) to note this condition, but it may be that the term "laryngeal isometric" is superior since there are other misuses of the larynx that obviously are manifestations of abnormalities of muscular tension. With this in mind we have evolved a new classification based on the laryngeal isometric, glottic and supraglottic lateral contraction states, antero-posterior contraction states, conversion aphonia, psychogenic bowing, and adolescent transitional dysphonia. PMID- 8517150 TI - Arachidonic acid metabolites (AAm) synthesis by the human hypertrophic ventricular folds (HVF). AB - A prospective study was carried out to assess the possible biochemical background of the AAm production by HVF in accordance with selected histological types and voice disorders. The mass of new tissue forming HVF in different clinical cases led us to suspect, according to our previous results, that PGs, LTs and other AAm may be involved in the pathogenesis of HVF. The level of PGE2 in HFV was lower (0.7 ng/ml) than in control (1.09 ng/ml) but not significantly; the PGI2 level (0.01 ng/ml) in HVF was also nonsignificantly lower than in normals, while thromboxane A2 synthesis by HVF (0.42 ng/ml) was significantly less than in control (0.99 ng/ml). On the basis of these results the hypothesis of a possible role of AAm in the process of HVF could not be confirmed. PMID- 8517151 TI - Fundamental frequency stability in functional dysphonia. AB - Functional dysphonia is a term applied to voice disorders for which there is an absence of apparent structural change in the larynx. The aim of this work was to investigate how functional dysphonia may differ acoustically from other types of dysphonia. Fundamental frequency profiles for steady vowels were generated using a software program called GLIMPES (Glottal Imaging by Processing External Signals). The fundamental frequency variations were found to be unimodal in normal individuals. In contrast, the variations for dysphonic patients were sometimes bi-modal or multi-modal due to the presence of subharmonics or low frequency modulations. The appearance of these patterns was generally related to the severity of the dysphonia rather than to its etiology. PMID- 8517152 TI - Histochemical and morphometrical ageing changes in human vocal cord muscles. AB - A histochemical and morphometrical study of thyroarytenoid and posterior cricoarytenoid human muscles was done in 43 human adults (38 males, 5 females) with ages ranging from 46 to 87 years. Vocal cord muscles were taken from laryngectomy specimens with carcinoma (25) and from autopsies (18), excluding those with neuromuscular diseases. In all cases the studied vocal cords were clinically and histologically normal in appearance. Only 2 patients received radiotherapy or chemotherapy. Posterior cricoarytenoid muscle was studied in 6 patients with larynx cancer. Mean diameter of thyroarytenoid muscle type I fibers (n = 128) was 38.46 microns and for type II 39.68 microns; fiber percentage values (n = 127) were 44.16% for type I and 55.84% for type II. Mean diameter (n = 6) of posterior cricoarytenoid muscle type I fibers was 42.69 microns and of type II 46.56 microns; type I fibers percentage was 66.15% and type II 33.85%. Statistical regression analysis revealed a progressive decrease in thickness of the mucosa and lamina propria in the right vocal cord along the ageing process. A low increase of endomysial tissue with a low decrease in perimysium in both vocal cords was noticed. In thyroarytenoid muscle, a low increase in type I fiber percentage and a decrease in type II fiber percentage were found. Posterior cricoarytenoid muscle showed a significant decrease in type I fiber percentage and diameter, corresponding to the same increase in variables of type II fibers. PMID- 8517153 TI - Variability analysis of Fo parameter in the voice of individuals with hearing disturbances. AB - The material of this investigation comprised a group of 18 patients with deep hypoacousis (over 70 dB) or complete deafness which, depending on the onset of the deafness, was divided into the 3 categories: congenital, early childhood to 3rd year of life, and postlingual. All of them underwent ENT, phoniatric and stroboscopy examinations; in 10, X-ray tomography of the larynx was also performed. The status of hearing ability was assessed by audiometric examinations using pure tones in air and bone conductions. The acoustic examinations comprising spectrographic and tonographic analyses were performed on an appropriate linguistic material including vowels, isolated words, sentences and reading text. The measurement of Fo was performed on isolated vowels. In order to characterise the degree and kind of periodicity disturbances the following parameters were estimated: the medium value of fundamental frequency, the range of Fo variability, the maximal change of period length from cycle to cycle, and its medium value (jitter). The results of the acoustic examinations revealed different degrees and kinds of periodicity disturbances depending on the depth of the hypoacousis and its onset. PMID- 8517154 TI - Is there a dissociation between emotional feelings and emotional signs in autism? AB - There is evidence that autistic persons are deficient both in the expression and recognition of emotion. Emotions are viewed here as in part genetically determined, inborn behaviours with great importance for social regulations. Both in phylogenetic and in ontogenetic development there is a transgression from emotion-bound or signal-reflex-like behaviour chains towards an experience-based coupling of emotional signals with events lying outside emotional exchanges. We conjecture that in childhood autism there is a deficit in linking biologically based emotional signals to emotional experiences and/or a deficit in linking these signals to a third element. Mesocortical areas with close connections to the limbic systems appear to be involved. PMID- 8517155 TI - Antecedents of severe affective (mood) disorders. Patients examined as children or adolescents and as adults. AB - A random selection was made of 100 adults, diagnosed as suffering from serious affective disorders (DSM-III), who had been cared for in the University Psychiatric Hospital in Geneva. One-third of this adult population (31%) was found to have consulted the child psychiatry service in Geneva (81.4% more than the general population). Patients suffering from manic disorders had consulted this service significantly more often during childhood. Our results showed that patients had a known psychopathology in childhood and adolescence that distinguished them from the control group (P < 0.005): 45% suffered from an affective disorder, in particular manic and hypomanic disorders (29%). The control group was made up of a group of randomly selected adult psychiatric patients, matched for age and sex, who had not been diagnosed as suffering from affective (mood) disorders, and who had also been examined as children or adolescents. Correlations between the childhood pathology and that of the adults were specially for manic disorders. These data are relevant for clinical assessment, treatment and prevention. PMID- 8517156 TI - Adverse temperamental characteristics and early behaviour problems in 3-month-old infants born with different psychosocial and biological risks. AB - In a prospective longitudinal study the influence of biological and psychosocial risk on early emotional and behaviour problems was investigated in a high-risk sample. Adverse characteristics of temperament and psychosomatic symptoms were assessed in 362 infants aged 3 months by observation of behaviour and parent interview instruments. Results showed cumulative negative effects of nearly equal significance of both biological and psychosocial risk on the severity and number of behavioural disturbances. No sex differences and no interaction of risk factors were found. Detailed analysis revealed that single risk factors were related to different patterns of infant behaviour problems. PMID- 8517157 TI - Autistic children and the object permanence task. AB - Many mentally retarded autistic children can understand the concept of object permanence, but, in comparison to developmental-age matched normal children, the behavioral strategies they employ in carrying out the Casati-Lezine Object Permanence Test are deficient and lead to failure. These deficiencies appear unrelated to interference of stereotypic or other bizarre behavior in task performance. Similar problem-solving deficiencies can be found in mentally retarded children who are not autistic, suggesting that the deficiencies themselves are less related to the social-communication deficits of autistic children, but more to the general problem-solving difficulties found in children with a lower developmental quotient. Nevertheless, the qualitative analysis of results shows a tendency in autistic children, despite their better developmental level, to use less coordinated and regular sequences to solve the task than normal or mentally retarded children. PMID- 8517158 TI - Developmental consequences of early eye contact behaviour. AB - Through early interactional exchange, infants acquire relevant information about themselves, their caretaking persons, and the relationship between themselves and their caretakers. Mutual eye contact is a highly adaptive behavioural system in this respect. There are, however, infants who avoid maternal eye contact and refuse their caretakers' attention. Gaze aversion of this kind is only reported to occur in the first months of life. It is interpreted as a first manifestation of a specific interaction. The present longitudinal study presents evidence for developmental consequences of early eye contact patterns. Infants who avert their gaze from their parents in the first months of life develop maladaptive relationships in terms of interactional harmony within 2 years, low degrees of psychobiological functioning, behavioural problems, and developmental delays for up to 6 years, and, at 2 years of age, explore new objects by means of manipulation for only short amounts of time. Infants with the expected good eye contact behaviour at that early age appear to have a more favourable development during the preschool years. PMID- 8517159 TI - Disintegrative psychosis of childhood. An appraisal and case study. AB - This study reports on five cases seen in a child psychiatry service in Northern India who met the criteria for disintegrative psychoses of childhood. Their clinical features were different from the described for autistic disorders of childhood supporting the validity of this disorder. The issues of diagnostic criteria and classification of disintegrative psychoses as distinct from autistic disorders is highlighted. PMID- 8517160 TI - Total mutism--a case report of a rare psychiatric disorder and approaches for behaviour therapy. AB - Total mutism, which is an extremely rare psychiatric disorder, was observed in an 11-year-old boy. He refused to speak a few weeks after starting school. Behavioural analysis showed that learning by model as well as positive and negative reinforcements were involved in the pathogenesis and maintenance of the disorder. The treatment followed principles of behaviour therapy by the use of operant techniques in the sense of contingency management methods. White noise, transmitted by earphones, was utilized to interrupt auditory feedback. It has been suggested that by this method anxiety would be diminished in the case of speech phobia. Within a few months of hospital admission the boy developed speaking behaviour progressing from barely audible breaths to sibilants of normal loudness. Short dialogues were possible after 18 months. The additional conduct disorder improved simultaneously with the increase in verbal and social skills. One year after hospitalization some social uncertainty persisted with tendencies to avoid demands. PMID- 8517161 TI - Sororicide in preteen girls. A case report and literature review. AB - All means of exploring the psychological and environmental antecedents of murder by a child should be used toward preventing lethal outcomes in future. The authors present the case of a ten year old girl who killed her sister with details of the sisters' relationship, the perpetrator's psychological characteristics and the family situation. Sibling-rivalry, family stressors, and the perpetrator's compulsive and narcissistic traits and preoccupation with a violent television fantasy are discussed. A literature review and suggestions for future research are provided. PMID- 8517162 TI - Living with a psychopathic personality: case history of a successful anti-social personality. AB - Anti-social personalities may be successful in life to a great extent. This is obscured by the tendency to study only those anti-social personalities who are imprisoned, in hospital, or undergoing therapy. We present a case history of Tom, a successful anti-social personality. He was 21 years old when the author lived with him for about 1 year. Tom used his skills to manipulate others and never went to prison nor was he ever ordered into therapy, although he did seek it out voluntarily for a brief period of time. Perhaps what kept him out of trouble with the law was that Tom stole only from friends and acquaintances, and not from strangers. He appeared to be an anti-social personality, but one who was fairly successful at it. Of course, the failure to develop non-manipulative close attachments to others means that the antisocial personality loses out by not having the kind of love, closeness, or stability of friendships that normal people can have. PMID- 8517163 TI - [The benzodiazepine story]. AB - Benzopyrylium salt (3) was converted by means of excess of hydrazine hydrate into a substance of a composition C22H26N2O4. The structure of this compound was elucidated by means of detailed NMR and mass-spectroscopic studies and the structure of 1-(3,4- dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3 benzodiazepine (4) has been proved. Conformation analysis was performed as well and it has been established that two conformers (A and B) exist in reversible equilibrium. The molecule contains a chiral centre and the enantiomers were separated via optical resolution. Two different 14C-labelled 4 were prepared for pharmacological studies. The compound is known as GrandaxinR in the medicinal practice (INN = tofisopam). PMID- 8517164 TI - [Additional data from the NMR investigation of tofizopam]. AB - The seven-membered ring of Tofizopam exists in two stable conformations in solutions. Separately detectable (Et)Me triplets of the conformers offered us a way for quantitative determination of conformer ratios. Temperature dependence of free enthalpy of conformers were calculated from the measured conformer ratios in different temperatures. Entropy component of the free enthalpy proved to be 35% of the whole at 36 degrees C. Half period of attaining equilibrium ratio of conformers was 2 hours at 36 degrees C. PMID- 8517165 TI - [Investigation of tofizopam impurities using high performance liquid chromatography]. AB - The identification and quantification of potential impurities of Tofisopam have been studied by high performance liquid chromatography. The best separation was obtained in a reversed phase system using a C18 stationary phase and 46:31:23 mixture of 0.01 M aqueous 1-hepatanesulphonic acid-sodium-acetonitrile-methanol as the mobile phase. System suitability parameters and method validation are also presented and discussed. The elaborated method was suitable for the determination of the conformational isomer ratio of Tofisopam in various solvents and for the evaluation of Challenge Test. PMID- 8517166 TI - [Pharmaceutical technology of Grandaxin]. AB - The physical chemical properties, stability and incompatibility of tofizopam (the active ingredient of Grandaxin tablet) were investigated. Tofizopam has low water solubility therefore experiments were made to increase it. The behaviour of tofizopam in acidic medium was studied and the degradation rates of it were determined at different pH. The composition of Grandaxin tablet contains well established excipients. The granulation can be made by high shear and fluidized bed process as well. The properties of tablets (strength, friability, disintegration, dissolution) are independent from the granulation process. The scaling up of the technology and the commercial production of the tablets are managed successfully. PMID- 8517167 TI - Psychiatry towards the year 2000. PMID- 8517168 TI - A comparison of paroxetine and placebo in depressed outpatients. AB - To compare the safety and efficacy of paroxetine (n = 167) and placebo (n = 169), data from 4 centres using the same protocol were pooled. A double-blind parallel group design was used, with therapy lasting 6 weeks. Significant differences between paroxetine- and placebo-treated patients were found on the major efficacy outcome variables by week 2 and on all efficacy variables by week 4 of the study. Improvement on the sleep factor of the Hamilton Rating Scale for Depression was found after 7 d. Observer and patient global efficacy ratings were in agreement by week 4. No serious adverse events occurred, and paroxetine had no clinically significant effects on vital signs or laboratory safety data. Side effects were more common on paroxetine and were similar to other serotonin reuptake inhibitors. In general, these were well tolerated and did not lead to dropout. Symptoms of increased arousal were not seen during early therapy. PMID- 8517169 TI - Risk factors for suicide in melancholia. A case-record evaluation of 89 suicides and their controls. AB - Eighty-nine inpatients with a primary severe depression and melancholia who had committed suicide were investigated. They were admitted to the Department of Psychiatry, Lund, Sweden between 1956-1969 and died before 1984. Matched controls were selected. Case records were evaluated at index admission to find suicidal risk factors in melancholia. Prospective ratings were compared. Women committing suicide had higher scores than their controls on the items unmarried, non compliance and suicide attempt but lower ratings on disharmonic childhood and non severe physical disease. Men committing suicide had higher scores on the items heredity for psychosis and a brittle or sensitive personality. For the latter item suicide was related to life-weariness. Suicide attempt was related to acute onset and lack of psychomotor retardation. Two suicidal processes were proposed for men: one related to aggression and one not. Social factors seem less important in the prediction of suicide in melancholia than in depression in general. PMID- 8517170 TI - Serotonin and amino acid content in platelets of autistic children. AB - The platelet levels of serotonin and the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were measured in 18 drug-free autistic (DSM-III criteria) and 14 age-matched healthy children. Serotonin was significantly increased while the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were significantly decreased in comparison with the controls. It is suggested that the decline of the amino acids in platelets from autistic children represents a biochemical marker related to infantile autism. PMID- 8517171 TI - Two-year stability of self-reported problems in an epidemiological sample of adolescents. AB - This study investigated the stability and change of problems reported by adolescents during a 2-year period. An epidemiological sample of 580 adolescents aged 11-16 at the initial assessment completed the Youth Self-Report on two occasions. We found high stability in the level of Youth Self-Report total problem scores. The highest stability was found for aggressive behavior. Problem scores tended to increase across time. This increase was greater for girls than for boys, especially for the somatic complaints syndrome. Of the adolescents who could be regarded as deviant at the initial assessment, 42% could still be regarded as deviant 2 years later. PMID- 8517172 TI - Mortality in major affective disorder: relationship to subtype of depression. The Danish University Antidepressant Group. AB - A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3-10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of > or = 18 and/or a Hamilton subscale score of > or = 9. Diagnostic classification according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years of observation. PMID- 8517173 TI - Mortality in Danish psychiatric long-stay patients, 1972-1982. AB - By use of the computerized, nationwide psychiatric case register in Denmark, 3 cohorts of psychiatric patients hospitalized for at least one year in 1972, 1977 and 1982, respectively, were identified and followed until April 1, 1988, regarding cause of death. A decline in overall excess mortality compared with the general population was seen from the 1972 cohort to the 1982 cohort irrespective of sex, age group and diagnosis. To analyse cause of death, 298 long-stay patients at Aarhus Psychiatric Hospital were followed for 5.5 years. Lung diseases caused the highest excess mortality. The authors emphasize that risk of death in long-stay patients below 50 years of age is still fourfold compared with the general population and point to the necessity of improving medical care. PMID- 8517174 TI - Standardization of a psychiatric screening test for use by general practitioners in Sardinia. Preliminary results. AB - The use of screening test for case-finding studies was introduced only a few years ago in Italy. This study aimed to define the degree of accuracy of the Italian version of the 24-item Self Reporting Questionnaire (SRQ-24) applied by general practitioners to their patients. The latter was carried out by comparing results with those obtained by means of the Present State Examination performed by a qualified psychiatrist. About 37% of patients interviewed could be considered as cases. In particular, 23% were affected by anxiety disorder and 14% by a depressive disorder. The receiver operating characteristic analysis showed a fairly good degree of accuracy of SRQ-24 for cut-off points between 7 and 8. PMID- 8517175 TI - Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. AB - Dopamine receptor dysfunction has been implicated in the pathophysiology of schizophrenia. Schizophrenic patients (n = 76) and control subjects (n = 53) were examined for allele frequencies in a 2-allele BalI polymorphism, causing a serine ->glycine amino acid substitution in the coding sequence of the dopamine D3 receptor gene. No statistical significant differences of allele frequencies or genotype frequencies could be found between the two groups. Neither were there any significant relationships between allele frequencies and a number of clinical variables within the schizophrenic subsample. However, if not corrected for multiple testing, an association was found between homozygosity and positive response to neuroleptic drugs. The present study does not provide evidence that the BalI polymorphism in the dopamine D3 receptor gene is involved in the pathophysiology of schizophrenia. Further investigations with an increased number and variety of patients concerning response to neuroleptic drugs and expression of the receptor in human brain should be performed to definitively exclude this hypothesis. PMID- 8517176 TI - Glans penis perception of Koro patients. AB - Koro is a form of sexual neurosis in which a reaction of acute anxiety accompanies the perception of decreased penis length from intra-abdominal traction. This study attempts to explore the glans penis perception of Koro patients by a grapho-motor projective test--DAPT (Draw-a-penis Test). This controlled DAPT investigation shows that Koro patients have significantly less perception of glans penis than the controls. This perceptual deviation in glans penis image is discussed in relation to the sexual-behavioral profile and Koro vulnerability of the patients. PMID- 8517177 TI - Studies of nocturnal penile tumescence and sleep electroencephalogram in patients with major depression and in normal controls. AB - Nocturnal penile tumescence (NPT), sleep electroencephalogram and testosterone secretion were investigated in 25 nonmedicated male patients with an acute episode of major depression. Twelve patients were reassessed after a stable remission and withdrawal of antidepressants. Four of the 25 patients had no NPT activity during acute depression, but this was reversed after recovery. The area under the NPT curve increased after remission, whereas all other NPT variables remained unchanged. Nocturnal testosterone secretion was enhanced after recovery, whereas the sleep structure remained unchanged. The NPT findings for the depressed patients did not differ from those for a control group, even though the latter group was younger. Hence, there are no general NPT changes that could be used to separate depressed patients and normal controls. However, a lack of NPT seems to be a possible, reversible symptom of depression in men. PMID- 8517178 TI - How well can a few questionnaire items indicate anxiety and depression? AB - There is a need for a short form questionnaire with known psychometric characteristics that may be used as an indicator of level of global mental distress. A weighted sum of 5 questions from the Symptom Check List (SCL) anxiety and depression subscales (SCL-25) correlates at r = 0.92 with the global SCL-25 score. The alpha reliability for the (5-item) short form questionnaire was 0.85%. Age differences seemed to be trivial, and sex differences were moderate. Descriptive statistics for short form scores in a large, representative sample are given. PMID- 8517179 TI - The role of sex and age in suicidal behavior. AB - Danish suicide rates for the last 65 years and data from 1976-1979 and 1989-1990, respectively, on attempted suicide in a representative Danish area show that marked changes have taken place in the distribution by sex and age of suicides and suicide attempters. Relatively more women are now taking their own life and, although suicidal risk still increases by age, the high-risk group also has come to include younger age groups. In contrast, relatively more men are attempting suicide, and the suicide attempters are getting older. Thus an equalization of the sexes has taken place, and the effect of age has become less pronounced. Both trends tally with the general trends in society. PMID- 8517180 TI - Death due to overdose of antidepressants: experiences from Norway. AB - During the last 20 years the suicide rate in Norway has doubled. This also applies to suicide by intoxication. Antidepressants comprise a constantly increasing part of the intoxication means used in suicides, as demonstrated in this article. The tricyclic antidepressants amitriptyline and doxepin, the most commonly used antidepressants in Norway, are also the two leading antidepressants causing death by intoxication. Less toxic antidepressants should be prescribed whenever possible. PMID- 8517181 TI - The toxicity of drugs used for suicide. AB - Death from suicidal drug overdose differs from other forms of suicide in that the drugs are often prescribed by the patient's physician. In 1987, 3 of the 12 most commonly taken drugs in completed suicide were antidepressants (dothiepin, amitriptyline and imipramine). Antidepressants account for approximately 15% of all drug overdoses. The differences in toxicity between antidepressants have been measured using fatal toxicity indices, which relate the number of deaths and the amount of drug prescribed. Results from the United Kingdom covering the years 1975 to 1986 have shown that older tricyclic antidepressants have a fatal toxicity index 5 to 8 times higher than that of new antidepressants such as mianserin. The limitation of barbiturate prescribing has been followed by a fall in deaths from these drugs. Hopefully in the future it might be possible either to prescribe less toxic antidepressants or to identify the patients at greatest risk of drug suicide and to prescribe for them the least toxic drugs. PMID- 8517182 TI - Admission of self-poisoned patients during one year at the Poisoning Treatment Centre, Copenhagen, Denmark. AB - The study comprises 541 patients admitted to the Poisoning Treatment Centre at Bispebjerg Hospital, Copenhagen; 440 of the patients were psychiatrically evaluated prospectively. The sex distribution was almost equal. In comparison with the normal population there was an overrepresentation of the age groups of 30-49 years old and of 18-19 years old. Only 20% were employed. Sixty-nine percent of the males and 40% of the females were living alone. Forty-six percent of the patients had some sort of abuse. Twenty-one percent suffered from psychotic disorder. Forty-eight percent had at least once before attempted suicide. The group was found to be at high risk of repeating suicide attempt according to a scale developed in the poisoning treatment centre in Edinburgh. The treatment of suicidal patients is discussed. PMID- 8517183 TI - The role of monoamines in suicidal behavior. AB - Cerebrospinal fluid (CSF), urine, platelet and neuroendocrine challenge tests of monoaminergic function give evidence of monoamines, especially serotonin, playing an important role in suicidal behavior. However, additional clinical, social and biochemical factors are necessary to better define suicide-prone psychiatric patients. PMID- 8517184 TI - Regional cerebral blood flow in affective disorder. AB - The results of two-dimensional cerebral blood flow (CBF) studies in depression and the results of measurements of regional CBF (rCBF) using single photon emission computerized tomography (SPECT) are briefly reviewed. A technical outline of both types of method is described. The majority of SPECT studies point to a decreased CBF in untreated patients with a tendency towards normalization, but other studies suggest that, following treatment, there is an increase above normal either from a decreased or an abnormally high initial level. One study has pointed to unipolar patients having lower flow in the right temporal and parietal lobes relative to normals, whereas non-endogenous patients did not differ significantly from normal controls. Bipolar depressives have been found to have higher flow values than normals in the parietal and temporal lobes in the left hemispheres. This relevant aspect or a possible relationship between type of depression and hemispheric asymmetry needs further study for full classification. Thus, most investigations designed to determine which brain structures might be involved in regulating affect have not been very successful, which may be a consequence of the biological heterogeneity of these disorders or of the limited spatial resolution of the techniques used for investigation. Even if some of these technical difficulties can be overcome with measurements of receptor kinetics supplemented, other biological variables that have proved valuable in psychiatry (such as rapid eye movement latency and biogenic amines) should be studied to find more precise biological markers for depressive illness. PMID- 8517185 TI - Psychotherapy of the suicidal patient. AB - Three different psychological theories of depression, the psychoanalytic, the behavioural and the cognitive-behavioural, and their psychotherapeutic principles are presented. A common, central aim of these therapies is to prevent suicide. But whenever suicidal ideation becomes dominant, the therapeutic method should be changed to a directive, counselling and reassuring form. PMID- 8517186 TI - Pharmacotherapy of the suicidal patient. AB - The incidence of self-poisoning and suicide accomplished with tricyclic antidepressants (TCA) is unacceptably high. TCA are undeniably highly toxic, and overdosage occurs frequently. This review presents data that more than suggest that the compounds are prescribed for patients for whom TCA treatment is not indicated. Therefore, the physicians must learn to face up to the benefit-risk elements with these drugs. As TCA for many years to come probably remain the drug of choice in treatment of many depressed patients, the only way out of this dilemma is to focus on prevention. In any event, more cautious prescribing of TCA outside hospital is desirable. PMID- 8517187 TI - The epidemiology of suicide and parasuicide. AB - This article analyses secular trends in suicide and parasuicide and provides support for the hypothesis that a true increase in these phenomena has occurred since the early 1950s up to at least the early or mid-1980s among the adolescent and young adult populations of Europe and North America, particularly young men. One of the potential causal mechanisms for this development, increasing secular trends in and lowering of age of onset for depressive disorders, is examined. Although it is difficult to assess whether the earlier age of onset observed for depressive disorders is reflected in an increase of suicide mortality at a lower age, there is indirect evidence to suggest that this might be the case. Studies show that lifetime parasuicide prevalence rates for the general population do not exceed and sometimes even remain below the rates for adolescents. Assuming that recall of past episodes remains constant throughout the life span, one possible explanation for this finding is an earlier age of the first-ever parasuicidal act. Since parasuicide is an important precursor of suicide, a lowering of age for first-ever parasuicides can be expected to lower the age for suicides and increase the overall lifetime risk. PMID- 8517188 TI - Improving bone marrow scintigraphy. A clinical and experimental study. AB - Today bone marrow scintigraphy is performed by imaging either the reticuloendothelial system by means of colloids or the hematopoietic marrow with granulocytes. When visualizing the marrow with radiolabeled colloids most of the administered activity will be taken up by the liver and spleen. To use granulocytes for bone marrow imaging is a comparatively expensive and complicated method. The aim of this study was to investigate the possibilities to shift the uptake of some of the injected activity from the liver-spleen and/or background to the bone marrow. Four small-sized colloids were evaluated in patients routinely referred for single photon emission computed tomography of the liver/spleen. After correction for attenuation and scattering of photons quantitative assessment of the activity in different organs was performed. Of the four colloids Nanocoll turned out to be the most favorable, thus this colloid was decided to be evaluated further. To assess the possibilities to improve the relative bone marrow uptake of Nanocoll, it was separated by gel filtration and different sized subfractions were injected into mice. None of the subfractions exhibited a more favorable bone marrow/liver-spleen ratio than the unseparated colloid. As blood clearance of a colloid is dependent on perfusion different measures were evaluated in mice aiming at either an increase in the blood flow to the bone marrow or a decrease in the liver-spleen perfusion. Nine different pharmaceuticals were tested. None improved the bone marrow uptake in relation to the liver enough to justify administration to humans. Fasting increased, however, the relative bone marrow uptake by approximately 15%. To evaluate the soft tissue background activity for colloids of different size a nanosized colloid (Nanocoll) and a larger colloid (Albu-Res) were investigated in an experimental mouse system and in humans. The latter were examined by quantitative single photon emission computed tomography as described above. The bone marrow activity relative to the soft tissue background activity was higher for the larger colloid in both mice and humans. By quantitative single photon emission computed tomography of the liver, spleen, bone marrow, and background the distribution of in vitro labeled autologous granulocytes and a colloid (Nanocoll) were assessed in patients. The activity of the bone marrow relative to the liver was significantly higher for granulocytes. The influence of scattered radiation is considerable in the vicinity of the liver. A technique for scatter correction with two opposing views was applied in a phantom and a human study. Both showed a considerable improvement of the visibility of the bone marrow close to the liver.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8517189 TI - Cerebrospinal fluid circulation and associated intracranial dynamics. A radiologic investigation using MR imaging and radionuclide cisternography. AB - AIMS OF THE PRESENT INVESTIGATION: Observations made in a preliminary study of pulsatile cerebrospinal fluid (CSF) and brain motions using MR imaging called for a reconsideration of the CSF flow model currently accepted. The following questions were addressed: 1) The nature of the CSF-circulation, e.g., the magnitude and pattern of pulsatile and bulk flow; 2) The driving forces of the CSF circulation and assessment of the role of associated hemodynamics and brain motions; 3) The major routes for the absorption of CSF. MATERIAL AND METHODS: CSF flow and associated hemodynamics were studied using gated MR imaging, in 26 healthy volunteers, 5 patients with communicating hydrocephalus and 10 with benign intracranial hypertension. Radionuclide cisternography was performed in 10 individuals with venous vasculitis. RESULTS AND CONCLUSIONS: 1) The CSF circulation is propelled by a pulsating flow, which causes an effective mixing. This flow is produced by the alternating pressure gradient, which is a consequence of the systolic expansion of the intracranial arteries causing expulsion of CSF into the compliant and contractable spinal subarachnoid space. 2) No bulk flow is necessary to explain the transport of tracers in the subarachnoid space. 3) The main absorption of the CSF is not through the Pacchionian granulations, but a major part of the CSF transportation to the blood stream is likely to occur via the paravascular and extracellular spaces of the central nervous system. 4) The intracranial dynamics may be regarded as the result of an interplay between the demands for space by the four components of the intracranial content, i.e. the arterial blood, brain volume, venous blood and the CSF. This interaction is shown to have a time offset within the cerebral hemispheres in a fronto-occipital direction during the cardiac cycle (the fronto occipital "volume wave"). 5) The outflow from the cranial cavity to the cervical subarachnoid space (SAS) is dependent in size and timing on the intracranial arterial expansion during systole. Similarly, the outflow from the aqueduct mirrors the brain expansion. The brain expansion is typically very small as evident from the minute aqueductal flow observed in healthy individuals. This expansion occurs simultaneously with an inflow of CSF and will be directed inwards towards the ventricular system. The brain expansion is of decisive importance for the formation of the normal transcerebral pressure gradient. 6) The instantaneous increase of flow in the superior sagittal sinus at the beginning of the systole reflects a direct pressure transmission via the SAS from the expanding arteries to the cerebral veins. It is contended that this early increase in venous pressure together with the volume wave is most likely an important prerequisite for sustaining normal intracranial pressure (ICP) and normal cerebral blood flow. This counter pressure should be reduced in hydrocephalus due to the decreased arterial expansion and could explain the reduced blood flow as well as an increased transmantle pressure gradient causing the ventricular dilatation. An increased pressure in the venous system is likely to be the cause of increases in ICP, including the increased pressure observed in benign intracranial hypertension (BIH). PMID- 8517190 TI - Radiological aspects of gamma knife radiosurgery for arteriovenous malformations and other non-tumoural disorders of the brain. AB - The aims of the thesis were to investigate stereotaxic procedures in radiosurgery for cerebral arteriovenous malformations (AVMs) and radiation effects of single session high-dose irradiation delivered by gamma knife on the human brain. Investigation of gamma knife radiosurgery in 1,464 patients constitutes the data base of this thesis. High quality stereotaxic angiography is the gold standard targeting imaging in radiosurgery for cerebral AVMs, particularly for small AVMs or residual AVMs after other treatments. For medium and large size AVMs, stereotaxic MR techniques can improve targeting precision and decrease irradiation volume as compared to stereotaxic angiography in selected cases provided that proper pulse sequences are used. Combined treatments, where embolization precedes radiosurgery, can improve amenability of the treatment for large AVMs. This is on condition that the partially embolized nidi are well delineated and the volume of the residual nidi has been decreased to a level where an optimum irradiation can be safely prescribed. Radiologically, adverse radiation effects (ARE) of gamma knife radiosurgery for cerebral AVMs are observed in 16% (131/816) of the patients. The ARE are observed as a focal low attenuation on CT or as a focal high signal on MR image without enhancement in 47% (61/131), and as a peripheral or homogeneous enhancing lesion in 48% (63/131). MR imaging is more sensitive than CT in detecting the ARE. 91% of the ARE are observed within 18 months after radiosurgery and 89% are seen to regress within 18 months. Clinically, symptomatic ARE are only observed in 6% (51/816) and only in half of them, i.e. 3%, are the symptoms permanent. The risk of ARE in radiosurgery for venous angiomas is higher as compared to AVMs. Other mechanisms have probably been employed. In gamma capsulotomy, the necrotic lesions and reaction volumes created by using multiple isocentres of 4 mm collimators are less predictable as compared to that by single isocentre. Volume effects and depreciation of the steep isodose gradient are hypothesised as the leading factors of the inconsistency. Based on the in vivo assessment of the radiation effects observed on the basically normal human brain it is concluded that irradiation volume is strongly related to the radiation effects and is one of the important considerations in decision making for radiosurgery. Volume of brain tissue exposed to irradiation could be minimised and precision of targeting could be maximised provided that a proper stereotaxic imaging is used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8517191 TI - Obligation and opportunity: family practice research regarding race and quality of care. PMID- 8517192 TI - The statistical power of family practice research. AB - To determine the statistical power of family practice research, we conducted a survey of all family practice studies published in 3 major family practice journals in 1988. Only 5 of 86 studies calculated statistical power, although 67 (78%) reported statistically nonsignificant results. Calculations of statistical power revealed that more than 80% of family practice studies had sufficient statistical power to detect medium to large effect sizes, but not small effect sizes, which some readers might deem clinically important. We conclude that the authors of family practice research studies do not pay enough attention to the issue of statistical power when reporting statistically nonsignificant results, leaving their readers in doubt as to whether a clinically significant effect could have been detected. PMID- 8517193 TI - Do tobacco companies avoid proper use of warnings in magazine ads? AB - By law, cigarette advertisements in magazines must contain one of four surgeon general's warnings and these warnings must be rotated quarterly. This study surveyed the top 13 magazines by paid subscription in the United States that accept cigarette advertising to determine if cigarette companies are compliant with this law. All issues of these magazines published during 1990 were surveyed yielding 1329 ads. Goodness of fit chi-square was used to compare observed distributions of each warning with the expected distribution. There were no significant differences in the number of times each warning appeared over the year or in each magazine. The tobacco industry as a whole appears to follow the guidelines of the Comprehensive Smoking Education Act, though 2 of 6 companies and 8 of 32 brands appear to advertise more heavily when using certain warnings and less heavily when other warnings are utilized. PMID- 8517194 TI - Esophagogastroduodenoscopy by family physicians phase II: a national multisite study of 2,500 procedures. AB - We have prospectively studied 1,783 upper gastrointestinal tract endoscopy procedures as performed by family physicians from thirteen separate office practices. Phase I of the study previously reported on 717 procedures in which patient management was enhanced, diagnostic yields were high, and biopsies were performed where appropriate. In Phase II, the data totaled 2,500 procedures representing 51.1 years of cumulative practice experience by the entire group. All cases were gathered prospectively and biopsies were confirmed by a pathologist's independent tissue analysis. In this series, family physicians were asked to record all complications, and to specify the exact manner in which performance of the procedure enhanced patient management. There have been biopsies in 1,230 (69% biopsy rate) Phase II cases with biopsy reports available in 1,194 (97% reporting rate) cases. There is pathological confirmation of the family physicians' visual diagnosis in 1,104 of 1,194 (93%) available biopsy reports for a 92% accuracy rate. There have been no complications, and the complication rate for the total series (1/2, 500) is now 0.0004. PMID- 8517195 TI - Why do patients continue to see the same physician? AB - In this study we examined the meaning that patients attach to continuity of care, an important construct of family practice and primary care. Structured oral interviews were conducted with 60 patients who were 35 years of age or older and who had sought health care from a single family physician for at least 15 years. The data included 10 domains that characterize patients' perceptions regarding long-term continuous care. The interview data were analyzed using ethnographic techniques. The main factors contributing to the maintenance of a continuous care relationship seemed to be patient familiarity with the physician, physician knowledge of the patient, patient satisfaction with care received, and patient confidence in the physician. Other factors were personal attributes of the physician, friendship with the physician, ease of communication with the physician, and professional growth of the physician. The availability of the physician and the location of the practice appeared to be reasons to start consulting a physician rather than to continue the relationship with a physician. PMID- 8517196 TI - Family relationships and depressive symptoms preceding induced abortion. AB - This study examines the association between depressive symptoms preceding induced abortion and dissatisfaction with family relationships. In a cross-sectional survey, 304 women undergoing a first-trimester abortion completed a short version of the Center for Epidemiologic Studies Depression Scale, the Family APGAR, and a researcher-designed questionnaire. Bivariate analyses revealed that depressive symptoms decreased as measures of age, educational attainment, Family APGAR scores, marriage, and subjective health increased. Depressive symptoms increased as measures of denial, difficulties communicating with male partners, pregnancy symptoms, contraceptive use, and dissatisfaction with choosing abortion increased. Controlling for the effects of these significant bivariate associations, increased depressive symptoms were independently predicted by Family APGAR scores, age, communications difficulties, pregnancy symptoms, contraceptive use, and denial. Low Family APGAR scores exhibited the strongest overall effect. Clinicians who encounter women experiencing depressive symptoms preceding abortion may wish to explore family relationships and the possibility of underlying family dysfunction. PMID- 8517197 TI - Patient and physician characteristics associated with perceived quality of care. AB - This study was undertaken to describe patient and physician sociodemographic characteristics that might be associated with the patient's perception of the quality of care rendered by his or her physician. A random telephone survey of 685 adult Kentucky residents showed that self-health assessment correlated positively, while patient education correlated negatively, with perceived quality of care. Perceived physician origin was related to the respondent's perceptions of quality of care, with native-born physicians perceived as supplying higher quality of care than their foreign-born counterparts. Cultural and communication issues might explain differences in perceived quality of care. PMID- 8517198 TI - Why do patients decline screening mammography? AB - Physician recommendation may not be sufficient to motivate patients to comply with health maintenance activities. During a physician visit, female patients over age 50 were reminded to schedule mammography; more than 10% overtly refused. A telephone questionnaire of 20 age-matched refusers and compliers was performed to assess knowledge, attitudes, behavior, and demographics. Refusers and compliers were similar in many respects; there was no significant difference in how the groups perceived their current health. Paradoxically, refusers had less knowledge of bad experiences with mammograms (p < .01). Refusers were more likely not to know if their insurance covered screening (p < .01), and were less likely to recall their physicians recommending screening even though recommendation was documented in the chart (p < .05). Refusers were less likely to have ever had a mammogram (p < .05). This subgroup of patients does not obtain mammograms, finds physician recommendation an insufficient stimulus for mammography, and considers insurance coverage a concern without investigating it. PMID- 8517199 TI - A comparison of physician-patient interaction at fee-for-service and HMO sites. AB - Research has begun to identify elements in the practice environment that influence practice styles and health outcomes. One key element known to influence physician-patient interaction is the type of treatment environment: fee-for service or health maintenance organization. Observers using the Davis Observation Code coded 82 physician-patient encounters in private practice settings and 72 encounters in a health maintenance organization. Populations were similar on all demographic measures except age, with health maintenance organization patients being older. Fee-for-service visits were shorter but included more coded behaviors per observation interval, resulting in equivalent total numbers of coded behaviors in each type of visit. Health maintenance organization visits included significantly more patient questions, preventive services, disease prevention, treatment planning, and discussion of substance use. Results may have reflected physician gender differences across sites or patient self-selection to sites rather than site differences. These results have implications for developing further research to explore treatment environment, process, and outcome. PMID- 8517200 TI - Continuing education in the physician's office: a pilot study for breast exams. AB - In response to a recent study indicating that primary care physicians were interested in receiving breast-screening education, an office-based training program was developed and delivered to fourteen physicians in Vermont and Florida. A nonphysician trainer and simulated patient provided instruction and feedback in clinical breast examination and in patient instruction in breast self examination. Measurements of physician palpation skills before and after the training showed substantial skill improvement, and the office-based session was found to be highly acceptable by all participants. PMID- 8517201 TI - The relationship of family structure and perceived family support to length of hospital stay. AB - Membership in an extended family has been viewed as beneficial, particularly in time of crisis, because of the support and resources that can be provided a member. In an attempt to confirm this view of the family, a study was conducted among Navajo Indians at the time of hospitalization. Instruments assessed family characteristics regarding extended or nuclear structure and the amount of family support the patient perceived. Scores obtained were correlated with the patient's subsequent length of hospital stay. Perceived support was related to length of stay (r = .28, p < .001), while family structure was not (r = .10, p = .10). As hypothesized, greater perceived support was associated with longer length of stay. The results are consistent with other findings suggesting social systems gain importance from function, not structure. If these results are confirmed in other groups, use of a simple tool for assessing support may assist in predicting length of hospital stay. PMID- 8517202 TI - Old Joe and the Marlboro man versus the Surgeon General. PMID- 8517203 TI - Historical aspects of lacunes and the "lacunar controversy". PMID- 8517205 TI - Pathogenesis of lacunar infarcts and small deep infarcts. PMID- 8517204 TI - The course and territories of cerebral small arteries. PMID- 8517206 TI - Lacunar syndromes. PMID- 8517207 TI - Clinical features of lacunar and small deep infarcts at specific anatomical sites. PMID- 8517208 TI - Clinical features of multiple lacunar and small deep infarcts. PMID- 8517209 TI - Lacunar syndromes due to non-ischemic small deep lesions. PMID- 8517210 TI - Binswanger's disease. PMID- 8517211 TI - Incidence, natural history, and risk factors in lacunar infarction. PMID- 8517212 TI - Diagrams of perforating artery territories in axial, coronal and sagittal planes. PMID- 8517213 TI - Computed tomography and magnetic resonance of subcortical ischemic lesions. PMID- 8517214 TI - Pathology of small artery disease. PMID- 8517215 TI - Liposuction-assisted revision and recontouring of free microvascular tissue transfers. AB - Liposuction has become a widely accepted and utilized technique that allows the aesthetic surgeon to improve regional definition and contour. Although the techniques of liposuction have now been extended to a variety of noncosmetic procedures as well, the application of this technique in the area of reconstructive surgery has lagged. To ascertain the applicability and effectiveness of liposuction for the revision of free microvascular tissue transfers we undertook a retrospective analysis of our free flap reconstruction cases that were revised and recontoured using liposuction. From this review of 12 cases we found liposuction to be a safe and effective technique for the delayed revision of free flap reconstructions of the head and neck region and lower extremity. PMID- 8517216 TI - The current status of autologous fat grafting. AB - The opinion of the majority of surgeons is fat grafting does not work. The fat cells do not survive transfer. Many have attempted the techniques only to become discouraged and abandon it. This article describes certain principles necessary for successful fat grafting: for harvesting use of a large-diameter syringe and needles, an atraumatic method of cleaning the fat cells, and an anaerobic method of storage. A method of autologous fat cell transfer including harvesting, processing, and injection of the fat is described. Long-term results are shown and limitations of the procedure are presented. PMID- 8517217 TI - Comparative experimental study of autologous adipose tissue processed by different techniques. AB - Different techniques for processing adipose tissue were tested in 40 Swiss Albino female mice. Our study established that the use of insulin did not show any positive effect on survival of adipocytes during their transplantation. Likewise, the use of a centrifuge machine, at high or low speed, for separating the adipose tissue components, completely destroyed the adipose cells and did not allow their survival. PMID- 8517218 TI - Local anesthesia for abdominoplasty, liposuction, and combined operations. AB - This article describes a procedure to perform abdominoplasty, liposuction, and combined operations under local anesthesia. With an anesthetic solution composed of 25 cc of 2% lidocaine, 25 cc of 0.5% bupivacaine, 1 cc of epinephrine or ornipresine, and 350 cc of saline solution, a satisfactory dilution with low concentration and lasting effects was obtained. After infiltration a large amount was lost in the incision, the dissection, and the resected dermofatty tissue. A small amount of anesthetic remained in the operated area to be metabolized by the liver. Low lidocaine levels were found in venous blood samples during surgery. This type of anesthesia is advised in minor, limited, and normal abdominoplasties in normal-sized patients, or major abdominoplasties in small patients. In liposuction procedures, it is possible to anesthetize the patient using the same procedure and operate in an equivalent area. As a high proportion of the infiltrated anesthesia was lost during the operation, a similar amount could be used to infiltrate and operate other areas so that an abdominoplasty might be combined with liposuction or mastoplasty. We have experience with 25 abdominoplasties and 21 liposuctions performed under local anesthesia. There were no complications related to local anesthesia and no one had unpleasant memories of intraoperative events. PMID- 8517219 TI - Clinical office anesthesia: the use of propofol for the induction and maintenance of general anesthesia. AB - Ambulatory surgery has become routine for many plastic surgery procedures. Anesthesia techniques including general anesthesia by inhalation and intravenous infusion and the dissociative technique have all been used successfully for outpatient anesthesia. Propofol (Diprivan), a relatively new agent, has proven to be a safe and effective general anesthesia agent for outpatient surgery. We report on our experience with propofol as an induction agent and continuous drip for general anesthesia maintenance in 100 consecutive outpatient, plastic surgery procedures performed in an office facility. Assessment factors were recovery-room time, nausea and vomiting in the recovery room and at home, hallucinations, patients' recollection of anesthesia experience, and overall patient satisfaction. PMID- 8517220 TI - Profiloplasty of the lower face by maxillary and mandibular anterior segmental osteotomies. AB - Maxillary and mandibular anterior segmental osteotomies (ASO) are ways to correct disharmony in the lip (contour, lip seal, and profile) and occasional dentoalveolar malocclusion. We performed 23 maxillary setback ASO, three maxillary advancement ASO, 21 mandibular setback ASO, and six mandibular advancement ASO in 28 patients to improve their lower facial profile. Other combined operative procedures include nine LeFort 1 osteotomies, four bilateral mandibular ramus osteotomies, two genioplasties, four mandibular angle contouring procedures, two reduction malar plasties, two piriform augmentations with bone graft, and a facelift for correcting of long faces, asymmetric faces, severe malocclusions, microgenias, prominent mandibular angles, prominent malar eminences, piriform recessions, and an aging face. Twenty five patients were satisfied with the results. Two patients complained of an over-recessed lip region, and one of septal deviation. There were no other significant complications or relapses throughout the followup period (9-30 months). Maxillary and mandibular ASO are effective, selective, relatively safe, and simple methods for correcting lower facial profile disharmony to attain a satisfactory aesthetic facial contour. PMID- 8517221 TI - Nostril and alar reshaping. AB - The authors recommend, when necessary, the use of external excisions for correcting variations in the shape of the nostrils and alae in the cleft lip-nose deformity, in primary rhinoplasties, and in secondary rhinoplasties. Their experience in the use of external incisions was originally stimulated by Millard's paper of 1960 which recommended different types of remodeling external excisions in his analysis of how to handle variations in the shape of the nostrils and alae. PMID- 8517222 TI - The subperiosteal lift. AB - The subperiosteal lift developed by Tessier is a technique for rejuvenating the face and emphasizing beauty. It is performed using two approaches: intraoral and bicoronal or precapillary. It entails a total subperiosteal undermining of the face beginning 2 cm over the orbits and continuing on the orbital rims, the zygomatic arches, and the malar bones. This allows total lifting of the soft tissues of the face (DMAS, deep musculo aponeurotic system). The lateral and vertical traction allows elevation of the superior two thirds of the face, eyebrows, and cheeks. Lifting pulls up from the forehead to the mandibular line. The fixation of the superficial layer of the temporal aponeurosis in traction to the upper part also has an effect on tissue elevation. The best candidates for this procedure are women in their late 30s or early 40s but can be used on those from 30 to 50 and more. It is highly specialized operation which requires substantial surgical experience both in selecting the patient and in execution. PMID- 8517223 TI - Corium transplantation cannula. AB - This article presents a newly designed instrument capable of being used for three surgical procedures:(1) removal of dermis (without epithelium) from a donor site, (2) dissection of specific muscles that cause cutaneous folds, (3) implantation of the dermis under a cutaneous depression or fold. PMID- 8517224 TI - Use of umbrella graft for nasal tip projection. AB - An adequate nasal tip projection is of the utmost importance for good nasal aesthetics. Conventional rhinoplasty procedures are not adequate for achieving nasal tip projection in "tips with inadequate projection" (TIP). This article describes our technique of using an umbrella-shaped cartilage graft to the tip. The graft is carved from caudal septal and alar cartilages. The results and advantages of the technique are discussed. PMID- 8517225 TI - Risk of blood contact through surgical gloves in aesthetic procedures. AB - Evidence of glove perforation, and therefore blood contact, was evaluated in 100 consecutive pairs of gloves used in aesthetic surgical procedures. The surgeon (38.3%) was more likely than the assistant (22.5%) to have exposure. In only 15% of these cases were they aware of the exposure. The left index finger (44%) was the most common location of perforation and 29 of the 32 holes (90.6%) were in cases that lasted more than 2 hours. PMID- 8517226 TI - The Minotaur syndrome: plastic surgery of the facial skeleton. AB - This article remarks on the possibility of recontouring the face by working on the facial skeleton with the sole purpose of softening the facial appearance. The author describes a one-step surgical procedure performed on a 38-year-old man who had serious social problems because of his aggressive and threatening facial appearance that contrasted with his gentle personality. The author coins the term Minotaur Syndrome to describe the discrepancy between the patient's true personality versus his negative facial appearance. PMID- 8517227 TI - [Special immunological aspects of the genital tract]. PMID- 8517228 TI - [Syphilis: current aspects in relation to HIV]. PMID- 8517229 TI - [Gonococcal infections]. PMID- 8517230 TI - [Disseminated gonococcal infection]. PMID- 8517231 TI - [Chlamydia trachomatis infections]. PMID- 8517232 TI - [AIDS: myths, untruths and reality]. PMID- 8517233 TI - [Ureaplasma urealyticum infections]. PMID- 8517234 TI - [Urethritis in men]. PMID- 8517235 TI - [Prostatitis]. PMID- 8517236 TI - [Salpingitis and its consequences for fertility]. PMID- 8517237 TI - [Urethral syndrome]. PMID- 8517238 TI - [Differential diagnosis of genital ulcers]. PMID- 8517239 TI - [History of venereal diseases]. PMID- 8517240 TI - [Vaginosis and vaginitis due to Trichomonas]. PMID- 8517241 TI - [Consequences of sexually transmissible diseases for male fertility]. PMID- 8517243 TI - [Maternal-fetal and perinatal transmission of sexually transmissible diseases. General principles and pathogen-dependent consequences]. PMID- 8517242 TI - [Sexually transmissible diseases and female infertility]. PMID- 8517244 TI - [Sexually transmitted viruses. General principles and classification]. PMID- 8517245 TI - [Genital herpes]. PMID- 8517246 TI - [Economic impact of HIV]. PMID- 8517247 TI - [Relationship between sexually transmitted viruses and genital cancer]. PMID- 8517248 TI - [Topical and laser treatment of virus-induced genital lesions]. PMID- 8517249 TI - [Interferons in the treatment of anogenital condylomas]. PMID- 8517250 TI - [Epidemiology of AIDS in Europe]. PMID- 8517251 TI - [Epidemiology of HIV-1 infection and AIDS in developing countries]. PMID- 8517252 TI - [Outpatient management of seropositive patients]. PMID- 8517253 TI - [Pathophysiology of the HIV virus]. PMID- 8517254 TI - [Prevention and risk management in economics and medicine: various observations]. PMID- 8517255 TI - [Hiv and AIDS infection. A. History, definition and classification]. PMID- 8517256 TI - [Natural history of HIV infection in adults]. PMID- 8517257 TI - [Opportunistic infections]. PMID- 8517258 TI - [AIDS and cancer]. PMID- 8517260 TI - [The contribution of social sciences to the prevention of AIDS]. PMID- 8517259 TI - [Hematological manifestations of AIDS]. PMID- 8517261 TI - [Cardiac manifestations in HIV infection]. PMID- 8517262 TI - [Pulmonary manifestations of acquired immunodeficiency syndrome]. PMID- 8517263 TI - [Reactions to AIDS risks in heterosexual relations: an attempt at typology]. PMID- 8517264 TI - [Endocrine manifestations of AIDS]. PMID- 8517265 TI - [AIDS and skin]. PMID- 8517266 TI - [Digestive manifestations in HIV+ patients. Enteric manifestations and diarrhea]. PMID- 8517267 TI - [Hepatobiliary manifestations in acquired immunodeficiency syndrome]. PMID- 8517268 TI - [Anal and perianal lesions observed in subjects infected with HIV virus]. PMID- 8517269 TI - [AIDS and digestive surgery]. PMID- 8517270 TI - [Nephrological manifestations of AIDS]. PMID- 8517271 TI - [Urological manifestations in HIV infection]. PMID- 8517272 TI - [Gynecological consequences of HIV infection]. PMID- 8517273 TI - [Definition of sexually transmissible diseases. Relationship between sexually transmitted diseases and HIV infection]. PMID- 8517274 TI - [Rheumatological manifestations of HIV infection]. PMID- 8517275 TI - [AIDS and ORL manifestations]. PMID- 8517276 TI - [Human immunodeficiency virus infection (HIV) in children]. PMID- 8517277 TI - [Home parenteral nutrition in patients with acquired immunodeficiency syndrome (AIDS)]. PMID- 8517278 TI - [HIV and vaccines]. PMID- 8517279 TI - [Prevention of HIV infection in the framework of an accidental intramural exposure]. PMID- 8517280 TI - [AIDS: Useful addresses]. PMID- 8517281 TI - [Sexually transmissible diseases and medical ethics]. PMID- 8517282 TI - [Sexual abuse with regard to children: a serious deed]. PMID- 8517283 TI - [Classification of sexually transmissible germs]. PMID- 8517284 TI - [Specimen collection and complementary tests]. PMID- 8517285 TI - MR angiography: present and future. AB - MR angiography is a rapidly evolving technique for noninvasive vascular imaging. Since 1985, when it was first shown to be clinically feasibls, the imaging techniques and hardware used for MR angiography have greatly improved. No longer is MR angiography a mere academic curiosity; it is already widely used to diagnose stenoses of carotid bifurcations and intracranial aneurysms. MR angiography supplements, and in some cases supplants, duplex sonography and CT for the study of suspected venous thrombosis in the chest, abdomen, and pelvis. With continuing technical developments, MR angiography most likely will replace conventional X-ray angiography in the presurgical workup of patients who are candidates for carotid endarterectomy or liver transplantation. Even MR angiography of the coronary arteries, considered implausible just a few years ago, has become feasible with the implementation of fast imaging techniques that suppress artifacts from respiratory and cardiac motion. Nonetheless, substantial problems remain that must be overcome before the full clinical potential of MR angiography can be realized. Despite the superficial similarities between MR angiograms and conventional angiograms, fundamentally different features of blood vessels are depicted. MR angiography is susceptible to a variety of artifacts that can exaggerate or simulate pathologic changes. The patient's cooperation is essential. The spatial resolution of MR angiography is inferior to its conventional counterpart, although the gap is being narrowed. This article reviews the basic principles of MR angiography and flow artifacts and surveys existing and future clinical applications. PMID- 8517286 TI - MR diagnosis of meniscal tears of the knee: importance of high signal in the meniscus that extends to the surface. AB - OBJECTIVE: The presence of intrameniscal signal in contact with the surface is a commonly used criterion for the diagnosis of meniscal tear. This signal presumably represents the actual tear in the meniscus. However, some menisci with signal that contacts the surface are noted to be intact at arthroscopy whereas other menisci that have no signal in contact with the surface are found to be torn. We investigated the relationship between the presence of a meniscal tear at arthroscopy and the location within the menisci of signal that contacted the surface. We hypothesized that patterns were present that would improve the accuracy of MR diagnosis of a meniscal tear. MATERIALS AND METHODS: We reviewed the MR and arthroscopic findings from 200 consecutive patients who had both knee MR examinations and knee arthroscopy. There were 108 medial and 58 lateral meniscal tears on arthroscopy. Each MR examination was reviewed for three aspects of intrameniscal signal: the number of images showing signal possibly or definitely contacting the surface, the specific surfaces involved, and the signal location. The coronal and sagittal images were evaluated separately. We correlated each of these features with the presence of a meniscal tear at arthroscopy. RESULTS: Menisci with signal possibly contacting the surface had the same frequency of tears (three tears in 33 menisci) as menisci without signal contacting the surface (15 tears in 194 menisci). More than 90% of menisci with signal contacting the surface on more than one image were torn, but only 55% of medial and 30% of lateral menisci with such signal on only one image were torn. In the torn menisci with signal contacting the surface, such signal was seen only on sagittal MR images in 31% of the medial menisci and 45% of the lateral menisci. Sixteen percent of the torn lateral menisci had signal contacting the meniscal surface in only the anterior two thirds of the meniscus, whereas this was true in only 2% of the torn medial menisci. Distinct patterns were not seen in the association between tears and signal contacting either the superior or the inferior surface. CONCLUSION: We found definite patterns in the location of intrameniscal signal that comes in contact with the meniscal surface. These patterns vary in the frequency of associated meniscal tears. Although menisci with internal signal in contact with the surface are usually torn, a tear is less likely if such signal is present on only one image. Tears may be identifiable on only one image plane. Tears in the anterior horn of the lateral meniscus are not uncommon. Knowledge of these patterns should help in the MR diagnosis of meniscal tears. PMID- 8517287 TI - Transient lateral patellar dislocation: diagnosis with MR imaging. AB - OBJECTIVE: Transient lateral patellar dislocation is frequently difficult to diagnose accurately on the basis of clinical findings. Accordingly, we studied the MR findings in 26 cases to determine if MR imaging is useful in establishing the diagnosis. MATERIALS AND METHODS: A retrospective review of 1450 MR examinations of acutely injured knees was performed to determine the MR findings resulting from transient lateral patellar dislocation. A distinctive constellation of MR findings reflecting the known mechanism of injury indicative of transient lateral patellar dislocation was found in 26 patients. Patellar dislocation was not clinically suspected before imaging in 19 (73%) of these 26 patients; most patients had been referred for suspected injury of the cruciate ligaments or menisci. Axial, sagittal, and coronal MR images were obtained in all patients, and all had clinical follow-up. Correlation of MR findings with surgical findings was possible in six. RESULTS: Specific components of the constellation of MR findings included disruption or sprain of the medial retinaculum in 25 (96%) of 26 patients, lateral patellar tilt or subluxation in 24 patients (92%), lateral femoral condyle contusion in 21 patients (81%), osteochondral injury in 15 patients (58%), and joint effusion in all 26 patients (100%). Concomitant injury to major ligaments or menisci was present in eight (31%). CONCLUSION: Our findings suggest that patients with transient lateral patellar subluxation have a distinctive constellation of MR findings that can be used to distinguish this entity from other common knee injuries. PMID- 8517288 TI - MR diagnosis of internal derangements of the knee: effect of field strength on efficacy. AB - OBJECTIVE: The purpose of the study was to test the hypothesis that diagnoses of internal derangements of the knee based on findings on MR images obtained at 0.5 T are as accurate as those based on findings on MR images obtained at 1.5 T. MATERIALS AND METHODS: The MR findings in 118 consecutive patients who had MR imaging of the knee at 0.5 T and subsequent arthroscopy were reviewed retrospectively. Ninety-two patients had arthroscopically proved tears of the medial meniscus, lateral meniscus, and/or anterior cruciate ligament. Sensitivity, specificity, and accuracy for MR evaluation of the medial and lateral menisci and anterior cruciate ligament were determined by using arthroscopy as the gold standard. The results were compared with similar data from 11 recently published studies in which MR images obtained at 1.5 T were used. To account for ambiguity in MR interpretation, the MR findings in this study were reanalyzed by using a five-point scale of diagnostic certainty, and receiver-operating-characteristic curves were constructed for each of the three anatomic structures examined. RESULTS: For tears of the medial meniscus, the sensitivity, specificity, and accuracy of MR at 0.5 T were 93%, 90%, and 92%, respectively. For tears of the lateral meniscus, the sensitivity was 81%, the specificity was 97%, and the accuracy was 93%. The sensitivity, specificity, and accuracy for detecting complete tears of the anterior cruciate ligament were 100%, 97%, and 97%, respectively. No clinically significant field strength dependent differences were found. CONCLUSION: The results suggest that, allowing for necessary discrepancies in imaging protocol, magnetic field strength is not a significant determinant of diagnostic reliability of MR assessments of internal derangement of the knee. PMID- 8517289 TI - Dorsal carpal ligaments of the wrist: normal appearance on multiplanar reconstructions of three-dimensional Fourier transform MR imaging. AB - OBJECTIVE: Three-dimensional Fourier transform MR imaging techniques can produce much thinner contiguous slices than are obtainable with standard two-dimensional Fourier transform MR imaging techniques. The improved spatial resolution and capabilities for interactive multiplanar displays allow improved visualization of small, complex anatomic structures such as the carpal ligaments. The purposes of this study were twofold: (1) to determine if the dorsal carpal ligaments can be visualized consistently with three-dimensional Fourier transform MR imaging techniques with multiplanar reconstructions and (2) to evaluate the size, shape, orientation, and right-to-left symmetry of the dorsal carpal ligaments in both wrists of 25 asymptomatic volunteers as a basis for future comparison when patients with suspected ligament injuries are seen. SUBJECTS AND METHODS: Both wrists of 25 asymptomatic volunteers were imaged with a three-dimensional Fourier transform MR imaging technique with commercially available equipment. A three dimensional graphic workstation was used to reconstruct oblique two-dimensional images in the long axes of the radiotriquetral and dorsal intercarpal ligaments in all 50 wrists. The size, shape, orientation, and right-to-left symmetry were determined by the author using the reconstructed two-dimensional images. RESULTS: The radiotriquetral ligament and dorsal intercarpal ligament were visualized in all 50 wrists. The radiotriquetral ligament consisted of a single band arising from the distal radius (next to Lister's tubercle) in 84% and had dual origins from the styloid process of the radius and Lister's tubercle in 16%. The dorsal intercarpal ligament consisted of a single broad band in 14% of wrists, was a branched structure with separate triquetroscaphoid and triquetrotrapezial fascicles in 44%, had completely separate triquetroscaphoid and triquetrotrapezial fascicles in 38%, and had a triquetrotrapezial fascicle larger than the triquetroscaphoid fascicle in 4%. The dorsal intercarpal ligamentous anatomy was symmetric in 16 of 25 volunteers. CONCLUSION: The major dorsal carpal ligaments can be visualized consistently when using three-dimensional Fourier transform MR imaging techniques and multiplanar reconstructions. The dorsal carpal ligaments are usually symmetric in size and morphology; therefore, MR images of the contralateral wrist may be used for comparison with MR images of a patient's injured wrist. The size and shape of the dorsal carpal ligaments are described for comparison with findings in patients who have suspected ligamentous injuries. PMID- 8517290 TI - Dedifferentiated liposarcoma of the extremities: imaging findings in four patients. AB - OBJECTIVE: The term "dedifferentiated" liposarcoma is used to describe a distinctive lesion in which a well-differentiated liposarcoma is juxtaposed with a high-grade nonlipogenic sarcoma. Dedifferentiated liposarcoma is probably the most common of all the dedifferentiated sarcomas, occurring almost exclusively in the mediastinum, the retroperitoneum, and the inguinal/paratesticular regions. We report the imaging findings in four cases of dedifferentiated liposarcoma of the lower extremities. MATERIALS AND METHODS: The radiologic images and clinical histories of four patients with histologically verified dedifferentiated liposarcoma were retrospectively studied. The mean age of the patients was 61 years (range, 33-79 years). All lesions occurred in the thigh. Spin-echo MR images were available for review in two cases and CT scans in the two remaining cases. Plain radiographs were available in all cases. RESULTS: All lesions were large, with a mean maximum size of 24 cm (range, 12-30 cm), and had a significant fatty component radiologically. Both MR and CT showed a well-delineated fatty component of the lesions and a closely apposed nonfatty region. Radiographs showed well-defined bone within one lesion, bone and amorphous calcification in another, and a single punctate calcification in a third. Two patients had a history of excision of a lipomatous lesion in the region of the mass. One patient had pulmonary metastases. CONCLUSION: The potential for deep well-differentiated fatty tumors of the extremities to dedifferentiate is not generally recognized. Although the different types of liposarcoma cannot be reliably distinguished with imaging studies, a well-defined nonlipomatous mass juxtaposed with a predominantly fatty tumor is suggestive of a dedifferentiated liposarcoma. PMID- 8517291 TI - Role of MR imaging in acquired and congenital cardiovascular disease. AB - The use of MR imaging for noninvasive cardiac diagnosis is still limited because clinicians currently rely on echocardiography and nuclear scintigraphy. Because of the development of MR techniques that can be used to evaluate contractile function and blood flow as well as cardiac morphology, greater applications of MR imaging are now likely to occur. Such a multifaceted use of MR imaging for the evaluation of cardiovascular disease should be encouraged by the continued development of fast imaging techniques. The purpose of this review is to describe the current clinical applications of MR imaging in acquired and congenital heart disease. The widespread use of MR imaging for cardiovascular diagnosis ultimately depends on its suitability as a comprehensive noninvasive imaging technique for ischemic heart disease and as a replacement for cardiac catheterization in congenital heart disease. PMID- 8517292 TI - 1992 ARRS Executive Council Award. Detection of deep venous thrombosis: prospective comparison of MR imaging with contrast venography. AB - OBJECTIVE: Preliminary reports have described the use of MR imaging for the detection of deep venous thrombosis. However, no prospective study comparing MR imaging with contrast venography (the gold standard) has been reported. Accordingly, we performed a prospective, blinded study of the efficacy of MR imaging in 61 consecutive patients with clinically suspected deep venous thrombosis. In cases of disagreement, additional testing was performed to determine the diagnosis. SUBJECTS AND METHODS: From June 1991 to February 1992, 61 patients with clinically suspected deep venous thrombosis were examined with venography and MR imaging. The average time between studies was 3 hr. In 21 of the 61 patients, the final diagnosis was deep venous thrombosis. RESULTS: For detection of deep venous thrombosis in the pelvis, the sensitivity of MR imaging was 100% (9/9) with a 95% confidence interval of 72-100% and the specificity was 95% (52/55) with a 95% confidence interval of 85-99%. In the thigh, the sensitivity (16/16) and specificity (43/43) were both 100% with 95% confidence intervals of 83-100% and 93-100%, respectively. In the calf, the sensitivity was 87% (13/15) with a 95% confidence interval of 60-98% and the specificity was 97% (36/37) with a 95% confidence interval of 86-100%. CONCLUSION: We found no statistically significant difference between MR imaging and contrast venography in the detection of deep venous thrombosis. This result suggests that MR imaging is at least as sensitive and specific as contrast venography in the detection of deep venous thrombosis. PMID- 8517293 TI - Skeletal growth lines seen on radiographs of newborn infants: prevalence and possible association with obstetric abnormalities. AB - OBJECTIVE: Skeletal transverse metaphyseal and vertebral lines, seen frequently on radiographs of infants and children, are usually believed to result from interrupted bone growth. Such lines have not been systematically studied in neonates. Accordingly, I determined the prevalence of growth lines on chest radiographs of newborn infants and assayed the gestational and obstetric abnormalities that occurred with these infants. MATERIALS AND METHODS: Chest radiographs were obtained (over a 4-year period) in 3687 neonates within the first 48 hr after birth for clinical indications. A single observer prospectively examined the radiographs for the presence of skeletal lines. When skeletal lines were seen on chest radiographs, lines in the pelvis were also sought when this region was imaged during the first 48 hr after birth. The medical records of affected neonates were reviewed to determine the presence and nature of potential in utero injuries. RESULTS: Skeletal lines were noted on chest radiographs of 200 neonates (5%) and appeared most commonly as "bone-within-bone" vertebral bodies and as transverse metaphyseal lines in the proximal humeri. Of affected neonates, 176 (88%) were born prematurely (< 38 weeks' gestation) and 59 (30%) had significant intrauterine growth retardation. Obstetric risk factors, which were varied and often multiple, were noted in 177 neonates (89%). The most common of these factors were pregnancy-induced hypertension (58 patients), multiple gestations (48 patients), drug abuse (30 patients), magnesium therapy (30 patients), prescribed maternal medications (27 patients), preterm labor before final labor (23 patients), and oligohydramnios (20 patients). In 23 neonates, no gestational complications were identified. CONCLUSION: Skeletal lines in the population of neonates who require chest radiography are relatively common, and often but not invariably appear to occur in the setting of potentially significant prenatal injury. It is speculated that these lines represent a tool for identifying and exploring causes of intrauterine growth disturbance. PMID- 8517294 TI - Diagnosis of acute appendicitis in children: spectrum of sonographic findings. AB - The sonographic appearance of the appendix and the periappendiceal region may vary greatly in children with acute appendicitis, depending on the extent and degree of inflammation and the presence or absence of perforation. Recognition of the typical and atypical sonographic features of appendicitis can be important in its diagnosis. In this report, we illustrate the spectrum of sonographic findings in 250 children examined with the graded-compression technique because of suspected appendicitis. Sixty-three (25%) of these children were subsequently shown to have appendicitis. PMID- 8517295 TI - Sonography of the thymus in healthy children: frequency of visualization, size, and appearance. AB - OBJECTIVE: The purpose of this study was to determine the frequency of visualization, the size, and the sonographic appearance of the normal thymus on sonograms of children 2-8 years old. SUBJECTS AND METHODS: Fifty children without symptoms referable to the thymus were scanned through the suprasternal notch and parasternal windows with a Diasonics DRF 100 scanner and a 7.5-MHz probe. The anteroposterior and longitudinal dimensions of the thymus were measured and the echogenicity of the thymus was subjectively assessed and compared with the liver and thyroid gland. No change was made in the time-gain compensation or overall gain settings. RESULTS: The thymus was completely visualized and measured in 47 (94%) of the 50 patients. The mean anteroposterior and longitudinal measurements were 1.4 and 2.5 cm, respectively, for the right lobe and 1.4 and 2.9 cm, respectively, for the left lobe. On longitudinal sonograms, the right lobe tended to have an inverted teardrop shape whereas the left lobe was either triangular or sickle shaped. The mean absolute dimensions of the thymus changed little with age, although the number of children in each age group was small. The internal echogenicity of the thymus most closely resembled that of the liver. CONCLUSION: The thymus is clearly and easily visualized on sonograms in the majority of children 2-8 years old, a much later age than reported previously. PMID- 8517296 TI - MR findings in a child with Guillain-Barre syndrome. PMID- 8517297 TI - Renal cell carcinoma occurring in a child 2 years after chemotherapy for neuroblastoma. PMID- 8517298 TI - White matter lesions and cerebral atrophy on MR images in patients with and without AIDS dementia complex. AB - OBJECTIVE: The objective of this study was threefold: to determine if the frequency of deep white matter changes and cerebral atrophy seen on MR images is significantly different between patients with and without AIDS dementia complex, to determine if certain patterns of white matter changes are more closely associated with AIDS dementia complex, and to determine if focal lesions within the white matter of the splenium are more common in AIDS dementia complex. MATERIALS AND METHODS: Forty-five patients with AIDS were clinically examined for AIDS dementia complex. MR images from these patients were retrospectively reviewed without knowledge of the clinical results. The presence or absence of white matter abnormalities and cerebral atrophy was evaluated by using graded scales and correlated with the presence or absence of AIDS dementia complex. RESULTS: Ten patients met the criteria for AIDS dementia complex. Eight of 25 patients in whom MR images showed abnormal signal intensity in deep white matter had dementia compared with two of 20 in whom MR showed no changes in deep white matter. The presence of these deep white matter abnormalities was not significantly different between groups with and without dementia (p = .08), although higher grades of deep white matter abnormality were more likely to be associated with AIDS dementia complex. Nine of 19 patients in whom MR images showed atrophy had dementia compared with one of 26 in whom MR showed no atrophy. Atrophy was significantly associated with AIDS dementia complex (p = .001). Eight of 15 patients in whom MR images showed abnormal signal intensity within the white matter of the splenium had dementia compared with two of 30 in whom MR showed normal signal intensity in this area. The degree of abnormality in the splenium was weakly associated with AIDS dementia complex (Kendall's tau = .471, p = .001). CONCLUSION: MR findings of cerebral atrophy and abnormal signal intensity in the splenium are associated with AIDS dementia complex. The presence of generalized deep white matter abnormalities does not differ significantly between patients with and without dementia, although more severe grades of white matter abnormality are more likely to be seen in patients with AIDS dementia complex. PMID- 8517299 TI - Cystic masses in the floor of the mouth: value of MR imaging in planning surgery. AB - OBJECTIVE: The purpose of this study was to determine the value of preoperative MR imaging for planning the best surgical approach for excising cystic masses in the floor of the mouth. In addition, different sequences and slice orientations were compared in order to develop a standard MR examination technique for this purpose. SUBJECTS AND METHODS: Eleven patients with cystic masses in the floor of the mouth were prospectively examined with MR imaging after palpation and sonography. The imaging protocol included T1- and T2-weighted spin-echo sequences, both unenhanced and contrast enhanced. The exact topographic relationship of these cysts to the surrounding muscles and the value of different MR techniques were analyzed. RESULTS: The mylohyoid muscle, which serves as a key structure in determining the exact position of a cystic mass, was visualized in all cases. T2-weighted images facilitated the primary diagnosis of cystic lesions, whereas T1-weighted images allowed the best visualization of anatomic details. Use of gadopentetate dimeglumine did not provide significant diagnostic information. Coronal and axial slices provided the best visualization of the topographic relationship of cyst and muscles. Sagittal slices were helpful only for midline lesions. In two cases, the choice between the intraoral and the cervical surgical approach was altered by MR imaging findings. CONCLUSION: MR imaging facilitates exact visualization of the location and extent of cystic lesions in the floor of the mouth and is useful for determining their relationship to the surrounding muscles. We conclude that MR imaging is an important adjunct to palpation and sonography in planning the best surgical approach. PMID- 8517300 TI - An approach to the creation of multimedia textbooks for radiology instruction. AB - We developed a standardized approach for creating computerized multimedia textbooks based on four principles: (1) multimedia textbooks should resemble printed books, (2) the creation of multimedia textbooks should be relatively inexpensive, (3) multimedia textbooks should be completely digital, and (4) the construction of multimedia textbooks should be simple. To facilitate this approach, an inexpensive, user-friendly multimedia authoring tool called The Annotator was used. The Annotator, a Hypercard-based program that runs on any Macintosh computer, helps authors rapidly create sophisticated radiologic multimedia textbooks. This program provides a textbooklike shell that can be filled with digitized media (video clips, audio clips, images, and text). This approach, which is applicable to any multimedia hardware platform, allows the authorship of multimedia textbooks that can be easily transported to any future multimedia platform. PMID- 8517301 TI - Interstitial MR lymphography with iron oxide particles: results in tumor-free and VX2 tumor-bearing rabbits. AB - OBJECTIVE: MR lymphography with interstitial injection of superparamagnetic iron oxide particles was optimized in normal rabbits by investigating the pattern of signal reduction in lymph nodes as a function of dose and time after administration. The optimized examination procedure was then used in a rabbit tumor model to study the potential of superparamagnetic iron oxide--enhanced MR lymphography in the detection of metastatic lymph node involvement. MATERIALS AND METHODS: The popliteal and iliac lymph nodes of 18 normal rabbits were imaged to study the dose response and time course of the effect of the contrast agent. For the dose response study, six doses of 2-50 mumol of iron per extremity were administered to three animals per dose, and MR images were obtained before and 12 hr after administration. For the time course study, 20 mumol of iron per extremity was administered to four animals, and images were obtained before and 6 hr to 42 days after administration. VX2 tumor-bearing rabbits were examined 12 hr after administration of 20 mumol (10 animals) and 50 mumol (three animals) of iron per extremity. Superparamagnetic iron oxide was injected into the foot pad of the hind limb. T1-, T2-, and proton density-weighted MR images were obtained with a 1.5-T unit. RESULTS: In normal rabbits, a profound and homogeneous loss of signal intensity was found with doses of 2-5 mumol of iron per extremity in popliteal lymph nodes and with doses of 20-30 mumol in the iliac lymph nodes. Superparamagnetic iron oxide caused maximal loss of signal intensity in both popliteal and iliac lymph nodes 12 hr after administration. In tumor-bearing rabbits, different degrees of metastatic displacement of lymph nodes were discernible, and even small metastases (3 mm in diameter) could be visualized when using the optimized examination protocol and the proton density-weighted spin-echo sequence. CONCLUSION: We conclude that interstitial MR lymphography with superparamagnetic iron oxide enables the detection of lymph node metastases and therefore is a promising technique for improved diagnostic imaging of lymph nodes in the staging of tumors. PMID- 8517302 TI - Einstein and Montefiore radiology departments: converging destinies. PMID- 8517303 TI - What's your forte? PMID- 8517304 TI - Further thoughts on writing clearly. PMID- 8517306 TI - Interval breast cancers. PMID- 8517305 TI - Early use of X-rays in the United States. PMID- 8517307 TI - Intrapulmonary lymph node: findings on high-resolution CT scans. PMID- 8517308 TI - Technical failures in CT arterial portography. PMID- 8517309 TI - Leiomyosarcoma of the pancreatic bed detected on CT scans. PMID- 8517310 TI - Abdominal tuberculosis mimicking a gynecologic tumor. PMID- 8517311 TI - Angiographic demonstration of a ureteroarterial fistula. PMID- 8517312 TI - Occipitotemporal vein: a superficial temporal vessel mimicking venous angioma on MR images. PMID- 8517313 TI - Radiology in Tbilisi: the legacy of 70 years of Soviet government. PMID- 8517314 TI - Pulmonary alveolar proteinosis. PMID- 8517315 TI - Detection and quantification of pulmonary artery hypertension with MR imaging: results in 23 patients. AB - OBJECTIVE: A study was performed to determine the value of MR imaging in detecting pulmonary artery hypertension and in determining pulmonary artery pressure semiquantitatively. SUBJECTS AND METHODS: MR studies were performed in 23 patients with pulmonary artery hypertension to measure right ventricular function (right ventricular ejection fraction, end-diastolic and end-systolic volumes, stroke volume), right ventricular wall thickness, and the diameters of the great vessels. The findings were compared with similar MR measurements made in eight control subjects. The cause of the pulmonary hypertension was primary pulmonary hypertension (eight patients), combined mitral valve disease (five patients), dilative cardiomyopathy (four patients), chronic pulmonary embolism (four patients), atrial septal defect (one patient), and pulmonary fibrosis (one patient). MR studies were done on a 0.5-T magnet using a double-angulation projection (equivalent to a four-chamber view) with a multislice-multiphase spin echo technique and a blood flow-sensitive fast gradient-echo sequence. Pulmonary artery pressures were verified by catheterization of the pulmonary artery. RESULTS: In patients with pulmonary artery hypertension, MR imaging showed right ventricular enlargement with hypertrophy, right atrial enlargement, and abnormal septal motion. Fast gradient-echo images showed tricuspid regurgitation in all cases. In cases in which the mean pressures in the pulmonary artery were greater than 70 mm Hg, systolic slow-flow phenomena were detected. Linear correlations were seen between the mean pressure in the pulmonary artery and the end-diastolic thickness of the right ventricular wall (r = .83, p < or = .0001), the diameter of the inferior vena cava (r = .73, p < or = .0001), and the diameter of the main pulmonary artery (r = .48, p < or = .02). CONCLUSION: Our results show that MR imaging is a useful noninvasive technique for the detection of pulmonary artery hypertension and for the semiquantitative assessment of pulmonary artery pressure. PMID- 8517316 TI - Pulmonary edema associated with mitral regurgitation: prevalence of predominant involvement of the right upper lobe. AB - OBJECTIVE: The symmetric distribution of pulmonary vascular congestion and edema caused by left ventricular heart failure associated with severe mitral regurgitation as seen on chest radiographs is well known. To our knowledge, only eight cases have been reported in which congestion and edema were confined to one lung or a portion of one lung. The purpose of this study was to determine the prevalence of asymmetric findings in these patients. MATERIALS AND METHODS: Three radiologists retrospectively and independently reviewed the plain chest radiographs of 131 patients with severe mitral regurgitation admitted to our institution during a 3-year period. Radiographs showing asymmetric vascular congestion or pulmonary edema were identified. Clinical records of these patients were studied to exclude other causes of pulmonary disease. RESULTS: Radiographic signs of vascular congestion and edema were present in 117 (89%) of the 131 patients. In 12 (9%) of 131 patients, these findings were localized or predominant in the upper lobe of the right lung. None of the patients had predominantly left-sided involvement. CONCLUSION: Pulmonary vascular congestion and edema involving predominantly the upper lobe of the right lung in patients with severe mitral regurgitation occurs more frequently than previously thought. This information is useful in the differential diagnosis of right upper lobe abnormalities, such as pneumonia. PMID- 8517317 TI - Appearance of pulmonary metastases on high-resolution CT scans: comparison with histopathologic findings from autopsy specimens. AB - OBJECTIVE: The purpose of this study was to compare the appearance of pulmonary metastases on high-resolution CT scans with the histopathologic findings in lung specimens obtained at autopsy. The factors considered were the appearance of the margins of pulmonary metastases, the location of relatively small nodules in relation to the secondary pulmonary lobules, and the detectability of lymphangitic spread of tumors and intravascular tumor emboli on high-resolution CT scans. MATERIALS AND METHODS: We studied 14 lungs obtained at autopsy that contained metastatic lesions. We used both microscopy and high-resolution CT to evaluate 87 metastatic nodules 5-20 mm in diameter for the appearance of their margins and to determine the location of 43 nodules that were less than 5 mm in diameter relative to the secondary pulmonary lobules. The detection of histologically confirmed intravascular tumor emboli and lymphangitic spread by high-resolution CT also was evaluated. RESULTS: On high-resolution CT scans, 38% of the nodules had well-defined, smooth margins, 16% had well-defined, irregular margins, 16% had poorly defined, smooth margins, and 30% had poorly defined, irregular margins. The well-defined, smooth margins on high-resolution CT scans corresponded histologically to an expanding type and to an alveolar space-filling type; the poorly defined margins, to an alveolar cell type; and the irregular margins, to an interstitial proliferative type. Some correlation was found between the histologic type of primary tumor and the CT appearance of the lesion's margins. As for small nodules, 12% were connected with the central bronchovascular bundle, 28% were on the perilobular structures, and 60% were apparently not in contact with these structures. Only two of the 11 lungs with histopathologically confirmed lymphangitic tumor spread and none of the tumor emboli were detected on high-resolution CT scans. CONCLUSION: The characteristics of the margins of metastatic pulmonary nodules noted on histopathologic examination correlated well with their high-resolution CT findings. Microscopic intravascular tumor emboli and lymphangitic tumor spread were difficult to detect on high-resolution CT scans, indicating a limitation of high-resolution CT in the diagnosis of pulmonary metastatic disease. PMID- 8517318 TI - CT findings in a proved case of respiratory bronchiolitis. PMID- 8517319 TI - Extrapleural fat collections: pseudotumors and other confusing manifestations. AB - Because thoracic fat is mobile and plastic, it can assume a variety of shapes and distributions. Fat collections can be confusing, and some can even mimic tumors. This essay highlights the variable and potentially confusing manifestations of normal thoracic fat on plain radiographs and CT scans. It does not emphasize fatty tumors, ordinary mediastinal lipomatosis, costal fat pads, or diaphragmatic hernias, as these topics have been reviewed recently. PMID- 8517320 TI - Screening mammography: value in women 35-39 years old. AB - OBJECTIVE: The value of screening mammography for detecting early breast cancer in younger women is not widely recognized. We review the results of screening mammography and of breast biopsies performed on the basis of mammographic findings in women 35-39 years old to determine the detection rate for breast cancer and the stage of breast cancers detected at mammographic screening in this age group. MATERIALS AND METHODS: Computer-tabulated results of mammography in women 35-39 years old who participated in a mobile mammographic screening program during the 36-month period from January 1989 to December 1991 were retrospectively reviewed with a standardized data collection form. Pathology reports from biopsies recommended on the basis of screening mammograms or follow up examinations (coned views/sonograms) also were reviewed. Data were compared with results of mammographic screenings and pathologic findings at biopsy in women 40-49 years old who participated in this screening program during the same period. RESULTS: A total of 5105 screening mammograms were obtained in women 35 39 years old. Of these, 4654 (91%) showed no abnormalities. Biopsy was recommended in 36 (< 1%). Eight biopsies showed carcinoma, intraductal in five and stage I infiltrating ductal in three. Mammograms showed calcifications in all cancers detected; two infiltrating cancers also had an associated mass. The number of breast cancers detected was 1.6 per 1000 screenings, comparable to our rate of 1.4 cancers per 1000 screenings in women 40-49 years old. Because the number of cancers detected was small, the 95% confidence interval for the ratio of detection rates was wide, ranging from 2.56:1 to 1:2.29. CONCLUSION: Early stage tumors in women 35-39 years old can be detected on mammograms. The breast cancer detection rate in women 35-39 years old was comparable to that for women in their forties in our population; however, our data do not exclude a more than twofold difference in detection rates between these two groups. These data should be considered in determining the value of mammographic screening in women 35-39 years old. PMID- 8517321 TI - Detection of pericolonic lymph nodes in patients with colorectal cancer: an in vitro and in vivo study of the efficacy of endosonography. AB - OBJECTIVE: Rectal endosonography is useful for the preoperative detection of perirectal lymph nodes in patients with rectal carcinoma, but some lymph nodes may be overlooked. The aim of this study was to compare the number of lymph nodes detected at sonography with the actual number and the pathology of the nodes found on examination of surgical specimens. MATERIALS AND METHODS: Colorectal specimens from 20 patients who had undergone resection of the colon (six patients) or rectum (14 patients) for carcinoma were selected for study. Sonography with 7-MHz endoprobes was performed with the bowel opened and submerged in water. The location and size of all lymph nodes that could be visualized in the pericolonic fat were marked on a drawing of the specimen. Distinction between malignant and benign nodes was not attempted. After fixation, pericolonic lymph nodes were identified by careful palpation, and their location and size were noted on a similar line drawing of the specimen. This was performed "blindly" without knowledge of the sonographic findings. By comparing the sonographic localization and size of the nodes with the histologic findings, it was possible to determine which nodes had been identified and which had been overlooked on sonograms. Preoperative endosonography had also been performed in 10 patients with rectal carcinoma, and the number of lymph nodes detected with this examination was compared with the results of the in vitro sonographic and histopathologic examinations. RESULTS: Histologic examination detected 205 lymph nodes in the 20 specimens. Sixty-four (31%) of them were seen on in vitro sonograms (25% of the benign nodes and 56% of the malignant nodes). The overall detection rates were 16% for nodes less than 5 mm in diameter, 56% for nodes between 6 and 10 mm, and 82% for lymph nodes larger than 10 mm. Preoperative rectal endosonography generally showed fewer lymph nodes (average, 1.2 nodes) than what was subsequently found with in vitro sonography (average, 2.7 nodes). CONCLUSION: Our study suggests that only approximately half of the malignant nodes in patients with colorectal carcinoma are visualized with endosonography of the surgical specimen. Even fewer nodes are visualized on preoperative in vivo examinations. The inability to detect more than 56% of metastatic lymph nodes makes preoperative endosonographic assessment less valuable than hitherto believed. This should be considered if sonographically guided biopsy of lymph nodes is considered as part of preoperative staging. PMID- 8517322 TI - Pathways of nodal metastasis in carcinomas of the cecum, ascending colon, and transverse colon: CT demonstration. AB - The distribution of regional lymph node metastases in carcinomas of the cecum, ascending colon, and transverse colon follows the vascular distribution in the ileocolic mesentery, ascending mesocolon, and transverse mesocolon. The location of these metastatic nodes can be recognized on CT scans when the anatomy of the vessels in the ileocolic mesentery and mesocolon is well understood. This knowledge is important in the preoperative staging of carcinomas of the colon for curative surgery and in the early detection of recurrent nodal disease after curative surgery. PMID- 8517323 TI - Value of contrast-enhanced CT in detecting active hemorrhage in patients with blunt abdominal or pelvic trauma. AB - OBJECTIVE: The purpose of this retrospective study was to evaluate the use of contrast-enhanced CT to show sites of active hemorrhage as a guide for surgical or angiographic treatment in patients sustaining blunt abdominal or pelvic trauma. MATERIALS AND METHODS: Twenty-six CT scans were reviewed to compare the location or locations of extravasated contrast material (representing hemorrhage) detected on CT scans with the site or sites of active hemorrhage determined by surgery (eight patients), angiography (14 patients), or autopsy (one patient). (The three remaining patients had no additional studies done.) The attenuation of extravasated contrast material on CT scans was measured and compared with the CT attenuation of an adjacent artery. The attenuation of clotted blood within the abdomen or pelvis was also measured in 20 other patients with blunt trauma. RESULTS: The locations of active bleeding as determined by extravasation of contrast material shown on CT scans included the pelvis (nine), spleen (five), retroperitoneum (four), kidney (three), liver (three), adrenal glands (one), and abdominal wall (one). Two patients had venous extravasation. The origin of bleeding was confirmed in all cases to correspond to the anatomic region in which extravasated contrast material was shown by CT. Three patients had only CT evidence of vascular extravasation of contrast material. The CT attenuation of active hemorrhage ranged from 85 to 370 H (mean, 132 H). A review of 20 additional CT scans that showed clotted blood in the abdomen or pelvis resulting from blunt abdominal trauma revealed a CT attenuation range of 40-70 H (mean, 51 H). These values were significantly different (p < .001) from the values for active hemorrhage. CONCLUSION: Active extravasation of contrast material (representing bleeding) can be detected in trauma patients who are physiologically stable enough to undergo CT of the abdomen or pelvis. Extravasated contrast material can be distinguished from clotted blood by measuring CT attenuation. CT accurately shows the anatomic location of bleeding and indicates the probable vascular origin. CT, therefore, can be used as a guide for angiographic or surgical intervention. PMID- 8517325 TI - Diffuse hepatic calcification after ischemic liver injury in a patient with chronic renal failure. PMID- 8517324 TI - Intraabdominal serous fluid collections after appendectomy: a normal sonographic finding. AB - OBJECTIVE: The significance of sonographic findings 1 week or less after appendectomy is difficult to evaluate without knowing the inconsequential abnormalities that may occur in these patients. Accordingly, we performed postoperative sonography on patients who had a normal course after appendectomy to determine the findings that can be considered normal within 1 week after surgery. SUBJECTS AND METHODS: Forty-four patients who had an appendectomy for acute appendicitis and who had normal findings at clinical follow-up 5 days and 6 months later were included in the study. In all patients, sonograms were obtained on the fifth postoperative day and interpreted by a radiologist who did not know the surgical findings. RESULTS: Ten fluid collections (23%) were found in the pericecal area, ranging in size from 10 x 10 mm to 40 x 20 mm. The collections were hypoechoic or anechoic, crescent-shaped, and immobile. Fluid collections were more common in cases of suppurative appendixes (6/20, 30%) than in cases of inflamed appendixes (4/19, 21%) and in retrocecal appendixes (3/9, 33%) than in normally located appendixes (7/34, 21%). However, the differences were not statistically significant (p > .05). CONCLUSION: Inconsequential fluid collections are detected with considerable frequency on postoperative sonograms 5 days after an appendectomy. Consequently, not every fluid collection should be considered an abscess. PMID- 8517326 TI - Percutaneous sclerosis of hepatic cysts to treat obstructive jaundice in a patient with polycystic liver disease. PMID- 8517327 TI - Massive splenic infarction and liquefactive necrosis complicating polycythemia vera. PMID- 8517328 TI - Determining the volume of prostatic carcinoma: value of MR imaging with an external-array coil. AB - OBJECTIVE: The size of prostatic carcinomas, as determined by estimations of the tumor volume, has a direct correlation with the histologic grade and stage. Therefore, accurate information about tumor volume can play an important role in determining appropriate treatment and establishing a patient's prognosis. Accordingly, we performed a study to assess the accuracy of MR imaging with external-array coils and the fast spin-echo technique for determining tumor volume in patients with prostatic cancer. SUBJECTS AND METHODS: In a prospective study, 20 patients with biopsy-proved prostatic cancer had MR imaging before radical prostatectomy. A 1.5-T system, a prototype external-array coil, and fast spin-echo technique were used to obtain axial T2-weighted (4000/120 [TR/TE]) MR images throughout the prostate and seminal vesicles. Contiguous 5-mm sections were obtained with a 256 x 256 or 256 x 192 matrix, 24-cm field of view, four excitations, and fat suppression. The volumes of cancer obtained with MR imaging and surgical specimens were determined independently. The areas of tumor were determined from individual axial sections by summing and multiplying by the section thickness. RESULTS: Seventeen of the 20 cancers were detected on MR images. A significant correlation between the volume of the tumor as determined with MR imaging and measurements of the specimens was observed (r = .81, p < .001). Four transition zone tumors were detected as zones of rather homogeneous decreased intensity. One important source of error for volumes determined with MR images was a limitation in the histologic specificity of MR imaging for the delineation of cancer; in some cases benign changes or normal prostates were interpreted as cancer. Another limitation was the presence of changes after biopsy that concealed portions of 10 of the 17 tumors visualized. CONCLUSION: The accuracy of the MR technique used was not sufficient for reliable prediction of tumor volume. The lack of specificity of T2-weighted MR imaging for cancer detection and the presence of changes caused by biopsy were major sources of error. PMID- 8517329 TI - Assessment of internal ureteral stent patency in patients with pyelocaliectasis: value of renal duplex sonography. AB - OBJECTIVE: The purpose of this study was to evaluate duplex Doppler sonography in the assessment of internal ureteral stent patency. SUBJECTS AND METHODS: Thirty three kidneys with pyelocaliectasis and an internal stent were studied with Doppler sonography and conventional sonography. Stent patency was proved by subsequent contrast-enhanced studies, direct inspection of the stent after removal, or clinical follow-up. RESULTS: The 11 kidneys with stent dysfunction had a significantly higher mean resistive index (0.78 +/- 0.08) than the 22 kidneys with patent stents (resistive index = 0.62 +/- 0.05) (p < .001). Eighty two percent (9/11) of kidneys with occluded stents had elevated resistive indexes. The two occluded stents with normal resistive indexes were found in kidneys without significant obstruction before stent placement. Ninety-one percent (20/22) of patent stents were associated with a resistive index of less than 0.70. In the two cases of falsely elevated Doppler studies, the resistive index was obtained only 24-36 hr after placement of the stent; however, the resistive index was at least 10% less than that before stent placement. No significant correlation existed between degree of pyelocaliectasis shown on real time sonography and stent status. CONCLUSION: In the presence of pyelocaliectasis after placement of an internal ureteral stent, intrarenal Doppler sonography can be used to accurately distinguish between patency and obstruction. Real-time sonographic findings (degree of pyelocaliectasis) are not useful in this clinical situation. PMID- 8517330 TI - A prospective evaluation of transvaginal sonography for detection of ovarian disease. AB - OBJECTIVE: Despite the expanding role of transvaginal sonography in routine gynecologic examinations, as well as in screening for ovarian cancer, recent reports have noted problems when using the procedure for detecting ovarian masses and visualizing the ovaries in postmenopausal women. Our study was designed to assess prospectively the capability of transvaginal sonography in evaluating the ovary and detecting adnexal masses. SUBJECTS AND METHODS: Transvaginal sonography was used to examine 113 ovaries in 59 women within 72 hr before gynecologic surgery. Ovarian size and echo texture were assessed, and a search was made for adnexal masses. Sonograms were interpreted without knowledge of the clinical history or results of physical examination, and the sonographic findings were compared with surgical and pathologic data. RESULTS: In the 22 premenopausal patients, 16 (76%) of 21 histologically normal ovaries were identified on sonograms, but only 13 (59%) of 22 adnexal masses. Lesions as large as 177 cm3 were not detected. In the 37 postmenopausal patients, 12 (20%) of 59 normal ovaries and six (54%) of 11 adnexal masses were identified. Five malignant masses (largest, 113 cm3) were not detected. CONCLUSION: In this selected population, our ability to detect normal postmenopausal ovaries and ovarian masses was suboptimal in a number of cases. Practitioners should be aware of potential limitations in the use of this technique alone to evaluate the ovary. PMID- 8517331 TI - Transvaginal sonography: a call for tempered enthusiasm. PMID- 8517332 TI - Direct inguinal hernia containing bladder carcinoma: CT demonstration. PMID- 8517333 TI - Senile amyloidosis of the seminal vesicles mimicking metastatic spread of prostatic carcinoma on MR images. PMID- 8517334 TI - [18F]2-fluoro-2-deoxyglucose-positron emission tomography correlation of gadolinium-enhanced MR imaging of central nervous system neoplasia. AB - PURPOSE: To correlate the findings of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MR imaging with positron emission tomography (PET) in the evaluation of central nervous system neoplasia. MATERIALS AND METHODS: Thirty-six lesions identified on noncontrast MR in 35 patients with biopsy-proved intracranial tumors were imaged with both T1-weighted Gd-DTPA MR at 1.5 T and [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET). Eighteen women and 17 men with a mean age of 47.1 years (range 22-72) were studied. The degrees of Gd-DTPA enhancement and FDG uptake were rated separately, and then all scans were reviewed together. FDG uptake was graded 1-5. RESULTS: Of the 35 lesions rated, 30 had Gd-DTPA enhancement and 28 of these were hypermetabolic (FDG accumulation greater than white matter) on PET (93% concordance). Twenty-six of 32 neoplastic lesions had Gd-DTPA enhancement. Twenty-four of these enhancing tumors were hypermetabolic. Only one lesion was completely missed on PET but identified on routine spin echo MR. CONCLUSION: Gd-DTPA MR and FDG-PET are complementary and there is a high concordance of Gd-DTPA-enhancing tumours displaying FDG hypermetabolism. Although FDG hypermetabolism and Gd-DTPA enhancement are usually suggestive of high-grade malignancy, anaplastic astrocytomas may not enhance with Gd-DTPA and can be hypometabolic. In addition, benign intracranial tumors (two cases of meningioma) and radiation necrosis can be associated with both FDG uptake and Gd-DTPA enhancement. PMID- 8517335 TI - Virchow's shackles: can PET-FDG challenge tumor histology? PMID- 8517336 TI - Radiologic-pathologic correlation. Capillary hemangioma of the meninges. AB - Hemangiomas are the most common tumor of the head and neck in children, including intracranial neoplasms. Capillary hemangioma in turn is the commonest type of hemangioma. Our case establishes that its anatomic distribution may include the intracranial compartment. We were unable to distinguish capillary hemangioma from meningioma based on imaging findings alone. PMID- 8517337 TI - Congenital clivus chordoma. AB - The authors report a case of a congenital clivus chordoma that caused cranial nerve palsy and hydrocephalus within a few days after birth. The tumor was well demonstrated by sonography, CT, and MR; the preoperative diagnosis was histologically confirmed after subtotal resection. PMID- 8517338 TI - Carcinomatous encephalitis (miliary metastases): lack of contrast enhancement. AB - Carcinomatous encephalitis is a rare form of brain metastasis in which there is diffuse miliary spread of punctate tumor nodules in a perivascular distribution. In this case, these tiny tumor nodules were seen throughout the cortical and basal gangliar gray matter only on T2-weighted images. Contrast-enhanced CT and T1-weighted MR images did not demonstrate these tumor nodules. PMID- 8517339 TI - Comparison of xenon-enhanced CT with ultrafast CT for measurement of regional cerebral blood flow. AB - PURPOSE: To compare an ultrafast CT method for estimating regional cerebral blood flow with a more commonly used xenon-enhanced CT method. METHODS: Xenon CT and ultrafast CT were used to estimate regional cerebral blood flow (rCBF) in 12 healthy beagle dogs. Measurements were obtained for left and right hemisphere, cortical gray matter, basal ganglia, and deep white matter. The ability of each method to show differences in blood flow between regions of high flow (gray matter) and low flow (white matter) was evaluated, both for large (> 0.75 cm3) and small (< 0.5 cm3) regions of interest. In addition, side-to-side differences in rCBF were evaluated to determine the minimum difference that would suggest a significant alteration in blood flow. RESULTS: There was less interanimal variance in absolute rCBF measurements obtained using xenon CT; ultrafast CT appeared to accentuate rCBF differences between high flow and low flow regions. There were strong side-to-side correlations in rCBF when measured by ultrafast CT, which suggests that this technique may be particularly useful in detecting focal alterations in rCBF restricted to one hemisphere of the brain. CONCLUSIONS: Ultrafast CT measures of rCBF compare favorably with those obtained using xenon CT. PMID- 8517340 TI - A computerized three-dimensional atlas of the human skull and brain. AB - PURPOSE: To develop an anatomic atlas of the human head based on a volume model derived from MR and CT. METHODS: Every voxel of this model was labeled by a neuroanatomist concerning its membership to a structural and/or functional region. A computer program was written that, instead of displaying precomputed images, allows the user to choose and compose arbitrary views. RESULTS: The user can subtract parts and ask for annotations just by using the mouse. Conversely, one can compose images by choosing objects from the list of anatomical constituents which is displayed on the screen. A set of dissection tools allows a "look and feel" that comes near to a true dissection. Operations that are not possible in a real dissection, such as reassembly or filling cavities, can be performed. CONCLUSION: The authors have developed a computerized model that can be used for anatomy teaching and also as a reference for radiologists or surgeons. To replace classical atlases, the spatial resolution must be improved and speed must approach real time. Functional imaging data (position emission tomography and single photon emission CT) can be added to the system. The system is mobile and can be situated in classrooms, operating rooms, reading rooms, and libraries. PMID- 8517341 TI - Gadolinium-enhanced MR in the evaluation of preoperative meningioma embolization. AB - PURPOSE: To evaluate the use of postembolization gadolinium-enhanced MR imaging as a means to judge the efficacy of tumor embolization. METHODS: Fifteen patients with meningiomas were prospectively studied. The following data were evaluated for each tumor: the percentage of vascular supply to the tumor arising from the internal and external carotid arteries; the percentage of the tumor embolized as judged by angiography, by MR imaging, and by CT scanning; the estimated blood loss according to the surgeon; and histologic evidence of necrosis as seen by the neuropathologist. RESULTS: The data reveal an excellent correlation between the amount of tumor embolized as estimated by MR and both the estimated blood loss at time of surgery and the presence of histological necrosis in the specimen. CONCLUSIONS: Postembolization gadolinium-enhanced MR is an excellent means to evaluate the efficacy of an embolization and offers certain advantages over CT and angiography. One important advantage of this technique lies in the fact that it can be performed immediately postembolization. PMID- 8517342 TI - Extended preoperative polyvinyl alcohol microembolization of intracranial meningiomas: assessment of two embolization techniques. AB - PURPOSE: To evaluate the efficacy of preoperative meningioma devascularization with small polyvinyl alcohol (PVA) particles. METHODS: In 34 patients with intracranial meningiomas, CT, MR, 1H MR spectroscopy, MR volumetric measurements, intraoperative ultrasound, and histopathologic findings were used to compare the efficacy of two embolization techniques: 1) administration of 150- to 300-microns PVA particles in the usual suspension, and 2) administration of 50- to 150 microns PVA particles in a highly diluted suspension. RESULTS: Angiography after embolization demonstrated the total elimination of tumor blush in all patients. Contrast-enhanced MR after the administration of 150- to 300-microns PVA particles revealed a reduction of tumor enhancement in only two out of 14 patients. Only after the use of small particles could significant tumor necrosis be depicted on MR and confirmed histopathologically after surgery. In 12 of 20 patients, 30% to 95% of the whole tumor was necrotic with 17% to 20% reduction of tumor volume in four cases, leading to recovery from the initial neurologic deficits. In three of 20 patients without sufficient steroid medication before the treatment, tumor swelling occurred. Postembolization MR disclosed a tumor volume increase of 10% to 20% in these patients. 1H MR spectroscopy of the tumors showed an increase of lactate and aliphatic lipid compounds after embolization, indicating tumor infarction. Surgical removal of effectively embolized meningiomas without significant blood loss was possible. The appearance of the tumor at operation, ultrasound examination, and the histopathologic examination of different parts of the tumor confirmed the preoperative MR findings suggesting necrosis. CONCLUSION: Extended microembolization with 50- to 150-microns PVA particles improves the surgical treatment of meningiomas, as compared with larger particle embolization. It may also be the only treatment required in older or high-risk patients. The protective effect of steroid medication before the endovascular treatment of meningiomas is suggested by our study. PMID- 8517343 TI - Preoperative intracranial meningioma embolization: technical considerations affecting the risk-to-benefit ratio. PMID- 8517344 TI - Balloon test occlusion of the internal carotid artery: change in stump pressure over 15 minutes and its correlation with xenon CT cerebral blood flow. AB - PURPOSE: To determine whether stump pressure changes significantly over time during temporary internal carotid artery (ICA) occlusion via an endovascular balloon, and to examine correlations between stump pressure changes and cerebral blood flow (CBF) as measured by xenon CT. METHODS: Seventy candidates for ICA sacrifice were evaluated preoperatively with a test occlusion of the cervical ICA using an endovascular balloon. Measurements of ICA stump pressure above the occlusive balloon through a distal lumen in the balloon catheter were made throughout the 15-minute test. During occlusion, CBF was measured with stable xenon CT techniques. Patients were then categorized according to CBF results. RESULTS: The stump pressure changed significantly (P < .001) during the occlusive period. On average, stump pressure increased 7.7 mmHg (12%). Patients determined by xenon CT to have an asymmetric decrease in CBF with balloon occlusion did not display the upward trend in stump pressures and were significantly different (P = .013) in that respect from patients who demonstrated either no CBF change or only minimal bilaterally symmetric decreases in CBF. CONCLUSIONS: Large overlaps among the groups prohibit the use of stump pressure changes as an accurate predictor of CBF or of stroke risk in an individual patient. However, these data suggest an autoregulatory mechanism in the cerebral circulation that evolves over a period of minutes in contrast to the traditional concept of cerebral autoregulation which is thought to occur in a matter of seconds. PMID- 8517345 TI - Aneurysm associated with a fenestrated basilar artery: report of two cases treated by endovascular detachable balloon embolization. AB - The authors report two cases of aneurysms originating at a fenestration of the basilar artery treated by endovascular placement of a balloon inside the aneurysm with preservation of the patent vessel. PMID- 8517346 TI - Venovenous extracorporeal membrane oxygenation: early CT alterations following use in management of severe respiratory failure in neonates. AB - PURPOSE: To describe brain CT alterations occurring after neonatal venovenous extracorporeal membrane oxygenation (V-V ECMO). METHODS: CT studies were prospectively obtained after V-V ECMO in 31 neonates with severe respiratory failure. Images were scored for cerebrospinal fluid space size, hemorrhage, and regions of decreased attenuation. RESULTS: Subarachnoid space enlargement at the interhemispheric fissure, frontal, temporal, or parietal convexity occurred in 21 of the 31 patients. When subarachnoid space enlargement was asymmetric (six of the 21), it was always isolated to or greater on the right. Ventricular enlargement was demonstrated in seven of the 31. Hemorrhage occurred in seven and regions of low brain attenuation in 11 of the 31 neonates. CONCLUSIONS: Increased sagittal sinus pressure caused by internal jugular vein ligation and cannulation of the superior vena cava may contribute to subarachnoid space enlargement by decreasing cerebrospinal fluid resorption at the arachnoid villi. Reduced incidence of cerebral hemorrhage with V-V ECMO, as compared with venoarterial (V A) ECMO, may relate to sparing of the right common carotid artery (it is ligated with V-A ECMO), and to routing of oxygenated blood to the right atrium with V-V ECMO rather than to the arterial circuit as with V-A ECMO. PMID- 8517347 TI - You pay a price when you fool with mother nature. PMID- 8517348 TI - Spinal injuries in children: role of MR. AB - PURPOSE: To define the clinical and prognostic role of MR in a pediatric population with spinal cord injury. METHODS: Fifteen children underwent MR 12 hours to 2 months postinjury using decoupled surface coils and ventilator support as needed. MR was correlated retrospectively with clinical, CT, and radiographic findings. RESULTS: On MR, of seven children with spinal cord neurologic deficits, four had hemorrhagic contusions, one had nonhemorrhagic contusion, one had extensive infarction, and one revealed a normal cord. All had persistent deficits on hospital discharge. Eight without cord neurologic deficit revealed no cord lesions on MR; this group included two with epidural hematoma, four with ligamentous disruption, and two with bone compression. CONCLUSIONS: Children may have extensive cord contusion and/or infarction with minor, remote, or no fracture dislocation. Because both hemorrhagic and nonhemorrhagic cord lesions found on MR were associated with significant, persistent cord deficits, the authors conclude that MR provides a practical tool for diagnosis/prognosis in children with acute/subacute spinal injury. PMID- 8517349 TI - MR demonstration of ectopic fourth ventricular choroid plexus in Chiari II malformation. AB - An enhancing nodule was seen on T1-weighted enhanced scans at the tip of the caudally displaced cerebellar vermis in three patients with Chiari II malformation. The enhancing fibrovascular nodule found at the base of the cerebellum in patients with Chiari II malformation represents ectopic choroid plexus and should not be confused with a pathologic mass. PMID- 8517350 TI - The split notochord syndrome with dorsal enteric fistula. AB - Split notochord syndrome with dorsal enteric fistula is an extremely rare congenital anomaly that may be associated with meningomyelocele or meningocele, and genitourinary anomalies. This case presented with an additional finding of bladder exstrophy, raising the possibility of a relationship between this syndrome and the OEIS complex. PMID- 8517351 TI - Noninvasive detection of increased glycine content by proton MR spectroscopy in the brains of two infants with nonketotic hyperglycinemia. AB - Using localized 1H-MR spectroscopy (1H-MRS) an inborn error of metabolism within human brain could be demonstrated, while 1H-MR imaging did not show any pathologic findings like demyelination. In two children suffering from nonketotic hyperglycinemia, the proton spectrum exhibited a large glycine signal at 3.55 ppm. In patient 1 (49-day-old girl), the pathologic signal of the inhibitory neurotransmitter glycine was of similar size in the parietooccipital white matter and in the basal ganglia region. In patient 2 (a 10-day-old girl), follow-up studies within the first 4 months of life revealed a time course of cerebral glycine content that differed from the course in plasma and cerebrospinal fluid. The continuing reduction of glycine in brain tissue corresponded more reliably with clinical findings than the stable values in plasma and cerebrospinal fluid. 1H-MRS allows the noninvasive demonstration of glycine in patients with nonketotic hyperglycinemia. This new technique may be useful to control the effect of a sodium benzoate therapy by monitoring the cerebral glycine concentration directly. PMID- 8517352 TI - Morphometric analysis of the corpus callosum using MR: correlation of measurements with aging in healthy individuals. AB - PURPOSE: To analyze changes of the human corpus callosum and MR midsagittal brain structures during normal aging. METHODS: A morphometric evaluation strategy for quantification of these brain structures on MR scans was developed. This computerized measuring program did allow the acquisition of more than 100 one- and two-dimensional parameters. RESULTS: During normal aging, the anterior parts of the corpus callosum (genu and anterior parts of the trunk) were significantly decreased, suggesting alterations of frontal and temporal interhemispheric fiber systems. Further changes were seen in callosal thickness and callosal width of the anterior parts of the corpus callosum. The profile area of the telencephalon was significantly reduced during normal aging. The size of the mesencephalon showed age-specific changes. CONCLUSIONS: The proposed computer program proved to be a powerful and reliable tool to get objective and reproducible quantitative data of corpus callosum and midsagittal brain structures. Specific age changes were found in the corpus callosum, indicating alteration of the frontotemporal interhemispheric fiber systems. PMID- 8517353 TI - Interuncal distance: marker of aging and Alzheimer disease. AB - PURPOSE: To evaluate the utility of a recently reported simple measure of brain atrophy on MR imaging, the interuncal distance (IUD). METHODS: Measurements of the IUD were made over a 12-month interval in 10 patients with probable early Alzheimer disease and in a comparison group of age-matched healthy control subjects. The measurements were made in both the transaxial and coronal planes. RESULTS: Significant group differences for the coronal measurement of IUD were found in both the absolute value of the measurement and the IUD corrected for head size. There was overlap in IUD between the disease and the control groups. These differences were not found for the transaxial IUD. Significant positive correlations of the IUD with Mini-Mental State Examination score and Clinical Dementia Rating Scale stage were observed. Over the age range tested, age was not significantly correlated with IUD in the sample. CONCLUSIONS: The interuncal distance (IUD) is not a useful screening measurement for Alzheimer disease. PMID- 8517354 TI - MR findings in two presumed cases of mild central pontine myelinolysis. AB - The authors describe two patients with presumed central pontine myelinolysis whose clinical symptoms were mild despite extensive intrapontine lesions evident on MR imaging. Enhancement of the lesions with Gd-DTPA was not observed in either case. It is suggested that the severity of findings on MR imaging does not necessarily reflect the severity of clinical symptoms of the disease. PMID- 8517355 TI - Comparison of dynamic CT and stable xenon CT in ischemic cerebrovascular disease. AB - PURPOSE: To investigate a new hemodynamic parameter that can be obtained by dynamic CT and that reflects cerebral blood flow (CBF), in patients with ischemic cerebrovascular disease. METHODS: CBF and hemodynamic parameters including the area under the time-dependent contrast-medium dilution curve (A) and mean transit time (MTT) were measured in 23 patients with ischemic cerebrovascular disease. They included 17 patients in the chronic stage (more than 1 month after onset) and six with acute occlusion of the internal carotid or middle cerebral artery (within 24 hours of onset). CBF measurement was conducted by inhalation of stable xenon during CT scan and the hemodynamic study was performed using dynamic CT. RESULTS: CBF in the territory of the middle cerebral artery had an inverse correlation with MTT. (A) divided by (MTT) defined as (f) had a significantly positive correlation with CBF (MTT = 18.66 - 0.495.CBF + 0.005.CBF2, r = .730, P < .001). CONCLUSION: This parameter (f) is thought to represent a relative CBF and it can be used in evaluation of the hemodynamic status in ischemic cerebrovascular disease. PMID- 8517356 TI - Arterial enhancement in acute cerebral ischemia: clinical and angiographic correlation. AB - PURPOSE: To investigate the cause and clinical significance of arterial enhancement (AE) in contrast-enhanced T1-weighted MR examinations after acute cerebral ischemia. METHODS: Contrast MR examinations and conventional angiograms of 17 patients studied following an acute ischemic event or an internal carotid occlusion were retrospectively reviewed. MR and angiographic studies were performed within 1 day of each other. The presence of AE was correlated with both angiographic findings and patient clinical status. RESULTS: AE was not confined to patients with angiographic evidence of complete arterial occlusion. Only 64% of patients demonstrating AE had complete occlusion angiographically. Complete arterial occlusion did not always correlate with AE. In two of nine patients with complete occlusion, no AE was identified. In five of 10 patients with AE, angiographic slow flow was identified. In patients without AE, no angiographic slow flow was identified. In the 64% of patients with AE, significant symptoms were identified. Patients without AE were either asymptomatic or had mild symptoms at the time of the MR study. CONCLUSIONS: Our data support the hypothesis that arterial slowing is the cause of AE, which appears to be an indicator of decreased brain perfusion. Such MR findings may add important supplemental information to those provided by conventional angiography. PMID- 8517357 TI - Hyperdense middle cerebral arteries identified on CT as a false sign of vascular occlusion. AB - PURPOSE: To evaluate the middle cerebral artery (MCA) on CT, including its relationship to cerebral infarction. METHODS: Thirteen patients with either a unilateral or bilateral hyperdense M1 segment of the MCA were evaluated. History of hypertension, diabetes, and hematocrit were obtained and compared with a control group of patients without a hyperdense MCA. RESULTS: None of the patients had a unilateral hyperdense MCA ipsilateral to a clinically identifiable stroke. Patients with a hyperdense MCA had a statistically higher hematocrit and also a higher prevalence of hypertension and diabetes mellitus than patients without a hyperdense MCA. The higher hematocrit may have increased the density of the blood, while both diabetes and hypertension are associated with calcification within blood vessel walls. CONCLUSION: A hyperdense MCA is not a reliable indicator of occlusion of this vessel or subsequent infarction. PMID- 8517358 TI - Fenestration of intracranial arteries with special attention to associated aneurysms and other anomalies. AB - PURPOSE: To determine the association of intracranial arterial fenestration and aneurysms. METHODS: We retrospectively reviewed 5,190 cerebral angiogram reports and identified 37 patients with arterial fenestrations. RESULTS: These 37 patients had 38 fenestrated arteries: 16 basilar, 10 vertebral, nine middle cerebral, and three anterior cerebral arteries. Seven of these patients had a total of 13 aneurysms, although only one aneurysm was at the site of a fenestration. The remaining aneurysm patients had fenestrations as unassociated findings. Other anomalies detected were two azygous anterior cerebral arteries, on dural arteriovenous shunt of the cavernous sinus, one extracranial arteriovenous fistula, and one developmental venous anomaly (venous angioma). None of the fenestrations were in the vessels directly involved with these associated lesions. The incidence of aneurysm at the fenestration was 7% (one in 16) for basilar artery fenestrations. Considering all fenestrations, the incidence of aneurysm at the site of fenestration was 3%. CONCLUSION: Our data show that the association of a fenestration with an aneurysm at the fenestration site is not different from the typical association of circle of Willis bifurcations with saccular aneurysms. PMID- 8517360 TI - Imaging of the saphenous vein graft bypass of the cavernous carotid artery. AB - PURPOSE: To describe the radiographic appearance of the interpositional carotid saphenous vein graft and to compare the efficacy of MR angiography with conventional angiography in determining graft patency and identifying graft irregularities. METHODS: The authors examined saphenous vein graft bypasses of the cavernous carotid artery in 14 patients using CT, MR, and conventional and MR angiography. RESULTS: The course of the graft was typically more inferior, lateral, and anterior than the course of the native vessel. Mild irregularities were found in four of the grafts, but all four "filled out" in a period of months. Time-of-flight angiography was comparable to conventional angiography in four of five patients. Phase-contrast angiography was comparable to conventional angiography in nine of nine cases. CONCLUSIONS: MR angiography is a useful screening modality in the postoperative evaluation of vascular grafts. PMID- 8517359 TI - Assessment of MR angiography versus arteriography for evaluation of cervical carotid bifurcation disease. AB - PURPOSE: To assess the accuracy of MR angiography alone in screening for vascular stenosis of the common carotid bifurcation. METHODS: Two hundred two common carotid bifurcations in 101 patients were evaluated with MR angiography and selective contrast arteriography. A two-dimensional time-of-flight pulse sequence was used to obtain sequential transverse images through the common carotid bifurcations. These images were reprojected with a maximum intensity pixel ray tracing algorithm. Both examinations were blindly graded as either normal or mildly stenotic (0%-29%), moderately stenotic (30%-69%), severely stenotic (70% 99%), or occluded. RESULTS: Of the 202 common carotid bifurcations, 119 were classified as normal-mild stenosis by contrast arteriography. In this category, MR angiography correctly identified 114 of these as normal to mild stenosis. Among 21 common carotid bifurcations graded as moderate stenosis by arteriography, 15 were correctly graded as moderate by MR angiography. Among 45 common carotid bifurcations graded as severe stenosis by arteriography, 41 of these were correctly graded as severe by MR angiography. There were 17 complete occlusions which were all correctly graded by MR angiography. CONCLUSION: MR angiography with its high rate of agreement with contrast arteriography can be regarded as an accurate screening method of the common carotid bifurcation. PMID- 8517361 TI - Pseudoaneurysm of the internal carotid artery: complication of deep neck space infection. AB - The authors describe a patient with a pseudoaneurysm of the internal carotid artery secondary to cervical adenitis. PMID- 8517363 TI - The hippocampus. PMID- 8517362 TI - Microanatomy of the excised human spinal cord and the cervicomedullary junction examined with high-resolution MR imaging at 9.4 Tesla. AB - PURPOSE: To study in detail the MR anatomy of the spinal cord and the cervicomedullary junction that could serve as a reference for clinical MR studies. METHODS: Specimens of fresh human spinal cord and formalin-fixed cervicomedullary transition zones were imaged with a 9.4-T vertical bore magnet. Using a multisection spin-warp pulse sequence the parameters were selected to produce essentially proton density images. RESULTS: The images obtained depict the microanatomical organization of the spinal cord and cervicomedullary junction. In the spinal cord, the central gray has the expected higher signal intensity compared with the white matter, which is, apart from its darker general appearance, characterized by the presence of a dense radially structured neuroglial framework of high signal intensity. Anatomically more complex regions such as the dorsal root entry zone, the adjacent posterior horn complex, and the crossing fibers of the cervicomedullary junction are seen as well as parts of the microvascular system. CONCLUSION: Although cellular details are still beyond the limits of this investigation, the images at 9.4 T show the spinal cord and cervicomedullary junction with detail comparable to low-power microscopic images of fixed sections, especially with respect to distinguishing gray and white matter, nuclei, tracts, and angioarchitecture. PMID- 8517364 TI - Correlation of single photon emission CT with MR image data using fiduciary markers. AB - PURPOSE: To describe our approach to mapping the functional information provided by single photon emission computed tomography (SPECT) onto the anatomic template provided by MR, and to determine both the number of markers required to achieve accuracy and the impact of voxel shape on accuracy. METHODS: Point-to-point iterative minimization using externally fixed fiducial markers was involved and computer simulations were performed. Two types of validation studies were performed using a phanton using a phantom of known dimensions. First, the spatial distortion that may be present in MR was investigated for spin-echo and gradient recalled echo images. Next, the accuracy with which the SPECT image could be transformed to match the MR template was analyzed. The method is also demonstrated in four cases of patients with epilepsy. RESULTS: Computer simulations indicated that for voxel dimensions we expected to use, eight fiduciary markers would consistently produce acceptable accuracy. Simulations also showed that more isotropic voxels would be more accurate if voxel volume is held constant. The spatial accuracy of both spin-echo and gradient-recalled echo images of a phantom was accurate to within 3 mm. When the SPECT image of the same phantom was correlated with the MR image using this technique, internal marker errors were never greater than 3 mm, and the mean error was 2.2 mm. CONCLUSIONS: Images from different modalities can be accurately correlated using multiple fiduciary markers. SPECT and MR images of the given dimensions can be correlated to within 3 mm. The technique aids in clarification of the nature of SPECT perfusion abnormalities and in their anatomic localization. PMID- 8517365 TI - Poststenotic signal loss in MR angiography: effects of echo time, flow compensation, and fractional echo. AB - PURPOSE: To evaluate with steady and pulsatile flow the influence of echo time, gradient strength and duration, and flow compensation on the degree of turbulent signal loss, factors that have been implicated in MR angiography's overestimation of the degree of stenosis. METHODS: We examined poststenotic turbulent flow in two models, one that created a turbulent jet and another that simulated a plaque like stenosis. The pulse sequence used in these experiments allowed for a single variable (flow compensation, echo time, or gradient strength) to be varied without changing the others. RESULTS: Poststenotic signal loss can lead to overestimation of the degree of a stenosis. The area of signal loss in the turbulent jet was influenced by fractional echo and flow compensation, but not by echo time. We found that the dominant mechanism in poststenotic signal loss is related to the strength and duration of the imaging gradients. CONCLUSIONS: Flow compensated sequences with reduced gradient strength and duration will reduce poststenotic signal loss and may lead to more accurate estimations of the extent of stenotic lesions. PMID- 8517366 TI - Rhabdomyosarcoma of the middle ear: imaging features in two children. AB - The imaging features are presented in two cases of rhabdomyosarcoma arising from the middle ear during childhood, an extremely rare and aggressive neoplasia. CT provides excellent information concerning the degree of bone involvement; contrast-enhanced MR imaging clearly delineates subcranial and/or intracranial extension. PMID- 8517367 TI - Neuroimaging features of neurenteric cysts: analysis of nine cases and review of the literature. AB - PURPOSE: To gain a better understanding of neurenteric (NE) cysts via correlation of imaging findings and surgical and pathologic data. METHODS: The medical records, imaging studies, surgical information, and pathologic material were retrospectively reviewed in nine patients with NE cysts, including seven proved and two very probable cases. RESULTS: NE cysts occurred in the cerebellopontine angle in one case and extended from the cerebellopontine angle to the C2 level in a second. In the latter patient and the remaining seven with intraspinal lesions, the NE cyst was always located anterior to the spinal cord. The most common myelographic and CT myelographic appearance was that of a lobulated intradural extramedullary (IDEM) mass. Two patients had an intramedullary NE cyst with a somewhat unusual appearing exophytic IDEM-appearing expansion that can be a characteristic feature of these lesions. MR imaging demonstrated the NE cyst to be isointense to hyperintense relative to cerebrospinal fluid on long TR sequences and isointense or slightly hyperintense to cerebrospinal fluid on T1 weighted images. These signal characteristics correlate with the high-protein content fluid within the cysts, usually described at surgery as milky or mucinous in character. CONCLUSION: The diagnosis of NE cyst should be considered when imaging studies reveal the presence of a lobulated IDEM or an exophytic intramedullary cystic mass, especially in association with anterior spina bifida or other vertebral anomalies. MR can uniquely confirm the cystic nature of these masses and is the method of choice for their imaging investigation. Because cyst recurrence can occur, MR should also be used for long-term patient follow-up. PMID- 8517368 TI - Metallic postoperative artifacts on cervical MR. AB - Spectroscopy of cervical diskectomy specimens obtained from sheep demonstrated that metallic susceptibility artifacts are produced by microscopic amounts of nickel, copper, and zinc. Sufficient quantities of metals to produce artifacts are deposited only by contact of metal drill bits and suction tips. If these instruments do not come in contact during surgery, susceptibility artifacts are not observed. PMID- 8517369 TI - Optimizing the diagnosis of hippocampal sclerosis using MR imaging. AB - PURPOSE: To establish the optimal imaging parameters and MR features of hippocampal sclerosis. METHODS: Twenty-five outpatients with intractable temporal lobe epilepsy and 10 control subjects were studied at 1.5T. Four features of hippocampal abnormality were specifically evaluated; increased hippocampal signal on T2-weighted images, decreased signal on T1-weighted images, hippocampal atrophy, and disruption of the internal hippocampal structure. RESULTS: Hippocampal sclerosis was diagnosed alone in 64% of patients and with ipsilateral pathology in a further 8%. In these 18 cases, increased hippocampal signal on T2 weighted images was seen in 77%, hippocampal atrophy in 83%, decreases signal on T1-weighted images in 83%, and disruption of the internal hippocampal structure in 89%. No abnormality was reported in any of the 10 control cases. CONCLUSIONS: Four MR features diagnostic of hippocampal sclerosis are reported. Inversion recovery images are very useful for identifying decreased signal in the hippocampus and loss of internal structure within the hippocampus. Based on an appreciation of these four features in optimized images, hippocampal sclerosis can be diagnosed with a high degree of accuracy and sensitivity. PMID- 8517370 TI - MR of the pituitary gland postsurgery: serial MR studies following transsphenoidal resection. AB - PURPOSE: To determine the MR appearance of the pituitary gland in the early and late postoperative periods in order to distinguish operative complications more effectively and to establish a postoperative baseline. METHODS: Ten patients were prospectively studied with MR following transsphenoidal resection of a pituitary tumor. Early postoperative studies were obtained at 2 to 8 days following surgery, late studies at 4 to 9 months in all patients and also at 12 to 16 months in five. Major observations were height of the pituitary mass and appearance of the surgical packing. RESULTS: Within 8 days following surgery, the height of the pituitary mass was unchanged in two cases, increased in three, and only minimally decreased in five. All decreased in height (average 54%) by 4 to 9 months. Gelfoam packing completely (five) or nearly completely (three) resorbed leaving a normal-size, although deformed, pituitary gland. Fat-packed resection defects persisted (two). CONCLUSIONS: In the early postoperative period, the appearance of the pituitary gland is similar in size to its preoperative appearance. Subsequent involution with packing resorption yields a smaller, deformed pituitary gland. PMID- 8517371 TI - CT findings in a case of pharyngeal rhinoscleroma. AB - The author describes the infectious disease rhinoscleroma and calls for its consideration in the differential diagnosis of nasal, pharyngeal, and tracheal masses seen in young immigrants. PMID- 8517372 TI - Infected epidermoid cyst of the sphenoid bone. AB - An infected epidermoid cyst presented on CT as a primarily dense, sclerotic expansile lesion in the greater wing of the sphenoid bone. Presumably, infection was responsible for the atypical appearance. PMID- 8517373 TI - Cerebral siderosis: a complication of anticoagulant therapy? AB - The authors report a case of cerebral siderosis, a rare disease that generally follows multiple small episodes of subarachnoid hemorrhage from any source, following long-term anticoagulation and minor head injury, and document the features on MR, which demonstrates characteristic hypointensity in the meninges on T2-weighted scans. PMID- 8517374 TI - Orbital wall infarction in sickle cell disease: MR evaluation. AB - Orbital wall infarction in a patient with sickle cell disease can present with periorbital swelling and subperiosteal collection and thus can mimic infection on CT. However, MR not only provides excellent morphologic information but, by characterizing the nature of the collection as containing blood, and by identifying bone marrow abnormality, can lead to the diagnosis of orbital wall infarction. PMID- 8517375 TI - Inadvertent intrathecal use of ionic contrast media. PMID- 8517376 TI - Menkes kinky hair syndrome. PMID- 8517377 TI - A pharmacist rebuilds after the 1992 L.A. riots. PMID- 8517378 TI - Communicating with the hearing impaired. PMID- 8517379 TI - APhA launches AIDS education program. PMID- 8517380 TI - Comparison of frequency, diagnostic and prognostic significance of pericardial involvement in acute myocardial infarction treated with and without thrombolytics. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI). AB - Data from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) trial were reviewed to describe the epidemiology of pericardial involvement in patients treated with or without thrombolysis, and to establish its role as a marker of the extent of myocardial infarction and its prognostic value. In both GISSI-1 (n = 11,806) and 2 (n = 12,381), a specific item regarding presence/absence of clinically detected pericardial involvement was included in the study forms. In GISSI-1, patients with ST elevation and depression at the onset of myocardial infarction were admitted, whereas GISSI-2 included only those with ST elevation. Results of univariate analysis are presented as Mantel-Haenszel-Peto odds ratios with 95% confidence intervals. Cox proportional hazards models were used to assess the independent prognostic significance of pericardial involvement for in-hospital and long-term mortality. The main results indicate that: (1) the incidence of pericardial involvement in patients treated with thrombolytic agents is approximately half of that in the control group (6.7 vs 12.0%); (2) the earlier is the treatment, the lower is the incidence of pericardial involvement; (3) pericardial involvement is strongly associated with infarction size, evaluated by electrocardiograms, creatine kinase peak and echo assessments; and (4) pericardial involvement is associated with a higher long-term mortality, but is not an independent prognostic factor (RR 1.02; 95% confidence interval 0.82-1.26). Pericardial involvement is a reliable bedside, cost-free marker of myocardial infarction size and poorer outcome. Because it may elude detection owing to its transitory and often short duration, it should be given greater attention. PMID- 8517381 TI - Morphologic changes induced by acetylcholine infusion in normal and atherosclerotic coronary arteries. AB - Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening. PMID- 8517382 TI - Early decrease in minimal luminal diameter after successful percutaneous transluminal coronary angioplasty predicts late restenosis. AB - Eighty-eight patients underwent serial coronary arteriography before, immediately after, 24 hours after and 7 +/- 2 months after successful percutaneous transluminal coronary angioplasty (PTCA) of 102 lesions. Severity of coronary obstruction was measured using quantitative digital angiography. Three groups of lesions were defined when comparing angiograms recorded immediately after and 24 hours after PTCA: group I--lesions with either no change or < or = 10% increase in arterial diameter stenosis after PTCA (n = 71); group II--lesions with > 10% increase in diameter stenosis after PTCA (n = 19); and group III--patients with total occlusion (n = 12). There were no significant differences in the severity of stenosis before or immediately after PTCA among the 3 groups of lesions. Twenty-four hours after PTCA the diameter stenosis was 14.2 +/- 6.3% in group I, 34.7 +/- 8.1% in group II and 100 in group III (p < 0.0001). At 7.1 +/- 2 months after PTCA the diameter stenosis was 21.2 +/- 16.8% in group I, 61.3 +/- 1.1% in group II, and 98.5 +/- 1.3% in group III (p < 0.0001). Restenosis (> or = 50% stenosis diameter) at follow-up per lesion was significantly greater in group II than in group I (73.6 vs 9.8%) (p < 0.0001). Thus, early angiographic study after successful PTCA stratifies lesions into angiographic subsets with low (group I) and high (group II) risk of coronary restenosis. PMID- 8517383 TI - Initial results and long-term outcome of coronary angioplasty in chronic mild angina pectoris. AB - To analyze the clinical and anatomic findings of patients undergoing coronary angioplasty for mild angina, and determine the short- and long-term outcome, a retrospective data bank analysis of 3,729 patients who underwent coronary angioplasty at the Mayo Clinic between July 31, 1980 and January 30, 1991 was performed. Of these patients, 217 (6%) had stable Canadian Heart Association class I or II angina at the time of the procedure and constitute the study population. Patients were followed for a median of 37 months after the procedure. The mean age of patients was 60 years; 82% were men. Prior myocardial infarction occurred in 22% of patients. Multivessel disease was present in 68% of patients, and mean left ventricular ejection fraction was 65 +/- 11%. Angioplasty was clinically successful in 196 patients (90%), 271 of 318 lesions (85%) were successfully dilated. There were no in-hospital deaths. Coronary artery bypass was performed during hospitalization in 12 patients (5.5%), and myocardial infarction occurred in 3 (1.4%); bypass or infarction occurred in 13 patients (5.9%). During follow-up of the 196 successfully treated patients, there were 9 deaths (4.5%), 16 patients (7%) developed myocardial infarction, 30 (15%) underwent coronary artery bypass surgery, and 36 (17%) developed severe angina. The probability of having any of these adverse cardiac events after 6-year follow up was 39%; an additional 24% of patients developed recurrent mild angina during follow-up. It is concluded that mild stable angina was an infrequent indication for coronary angioplasty at the Mayo Clinic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517384 TI - Predictors of major ischemic complications after coronary dissection following angioplasty. AB - Coronary dissection is a major cause of abrupt arterial closure after coronary angioplasty but may also be associated with no discernible event. Deciding which dissections should receive further treatment is often a dilemma if the artery remains patent. This case-control study examined predictors of major ischemic complications after coronary dissections. Fifty-eight patients with coronary dissections, but a patent artery at the completion of the angioplasty procedure, subsequently had in-hospital abrupt arterial closure, acute myocardial infarction, emergency coronary bypass surgery, or died; they were matched to 58 control subjects with dissection but no event. Analysis of each angiogram was performed with the examiner unaware of patient's history. Baseline angiographic and clinical characteristics of cases and controls were similar except for an excess of current smokers among the cases (31 vs 16%; p = 0.048). Residual luminal diameter at the dissection site was 1.2 +/- 0.6 mm (cases) versus 1.6 +/- 0.6 mm (controls; p = 0.001) with relative stenosis of 59 +/- 21% vs 43 +/- 21%, respectively (p = 0.0001). Dissections among cases were longer than among controls (11 +/- 7 mm vs 7 +/- 4 mm; p = 0.001). No significant difference was found in dissection morphology using 2 classification schemes or in final Thrombolysis in Myocardial Infarction study flow grade. Transient occlusion during the procedure, however, occurred in 47% of cases versus 5% of controls (p = 0.0001). Transient occlusion, residual percent stenosis > or = 70%, and dissections > or = 6 mm were independently predictive of major ischemic events. PMID- 8517385 TI - Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. The Simvastatin Pravastatin Study Group. AB - The efficacy and safety profile of simvastatin and pravastatin across their most commonly recommended dosage ranges were compared in a double-blind, parallel, multicenter study in 550 patients with primary hypercholesterolemia. The study consisted of a 6-week placebo period followed by 18 weeks of active treatment. Patients were randomized to 10 mg of simvastatin or pravastatin once in the evening; doses were titrated at 6-week intervals to a maximum of 40 mg/day if the low-density lipoprotein (LDL) cholesterol remained > or = 130 mg/dl (3.4 mmol/liter). Baseline characteristics were similar in both groups. At the end of the study with simvastatin and pravastatin, respectively, 30 and 14% continued to take the 10 mg dose and 48 and 66% were titrated to the maximal dose. After 18 weeks of treatment with simvastatin and pravastatin the mean percent decreases from baseline were, respectively, for total plasma cholesterol 27 and 19% (p < 0.01 between groups), for LDL cholesterol 38 and 26% (p < 0.01 between groups), for very low density lipoprotein cholesterol 30 and 16% (p < 0.01 between groups), and for triglycerides 18 and 14% (p < 0.05 between groups). The mean percent increase from baseline in high-density lipoprotein cholesterol was 15% with simvastatin compared to 12% with pravastatin (p < 0.05 between groups). The efficacy goal of LDL cholesterol < 130 mg/dl was achieved in 65% of the patients treated with simvastatin versus 39% of those treated with pravastatin (p < 0.001). There was no significant difference between groups in the frequency of drug-related adverse experiences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517386 TI - Symptoms and electrocardiographically documented rhythm preceding spontaneous shocks in patients with implantable cardioverter-defibrillator. AB - During a follow-up of 24 +/- 20 months after treatment with an implantable cardioverter-defibrillator (ICD), 101 of 241 patients (42%) received > or = 1 spontaneous ICD shocks with documentation of the rhythm leading to shock by Holter or telemetry monitoring or stored electrograms by the device. Sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in 67 of the 101 patients (66%) with electrocardiographically documented shocks, nonsustained VT in 4 patients (4%), supraventricular tachyarrhythmias in 41 patients (41%), and normal sinus or pacemaker rhythm in 10 patients (10%). No, mild (palpitations and/or mild dizziness) and severe symptoms (presyncope/syncope) preceded spontaneous ICD shocks in 20 (30%), 33 (49%) and 27 (42%) of the 67 patients, respectively, with electrocardiographically documented VT or VF, and in 23 (56%), 16 (39%) and 1 (2%) of the 41 patients, respectively, with electrocardiographically documented supraventricular tachyarrhythmias. Three of the 4 patients with nonsustained VT had mild symptoms, and 1 patient with nonsustained VT had presyncope. None of the 10 patients with spurious discharges during normal sinus or pacemaker rhythm had symptoms preceding the ICD shocks. It is concluded that (1) most patients with either electrocardiographically documented VT/VF or a non-VT/VF rhythm preceding spontaneous ICD shocks have no or mild symptoms preceding the shock, and (2) severe symptoms preceding ICD shocks suggest sustained VT or VF as the underlying rhythm, although severe symptoms rarely occur in patients with supraventricular tachyarrhythmias or nonsustained VT. PMID- 8517387 TI - Cine magnetic resonance imaging and color Doppler flow mapping in infants and children with pulmonary artery bands. AB - Cine magnetic resonance imaging (MRI) and color Doppler flow mapping were performed in 12 infants and children (aged 3 to 35 months) after pulmonary artery banding to define the anatomy and physiology of the right ventricular outflow tract and evaluate the anatomy. MRI was performed using a 1.5 Tesla magnet in the sagittal, axial and oblique views with all patients studied in the 24 cm head coli following adequate sedation. High-resolution cine MRI was obtained in all patients and the narrowest flow diameter on cine MRI correlated well with the pressure gradient measured across the band in 11 patients at cardiac catheterization or surgery (r = -0.95). Signal loss was always seen distal to the band associated with turbulent flow as seen by color Doppler flow mapping. Signal loss in cine MRI was also seen proximal to the band. The length of this proximal signal void also correlated well with the pressure gradient measured across the band (r = 0.91) and was closely matched by the zone of proximal spatial acceleration defined by digital computer analysis of color Doppler flow map images (r = 0.89), which also demonstrated low grade variance associated with the laminar accelerating flow stream. The position of the band was accurately defined by cine MRI which identified inadequate pulmonary artery banding in 2 patients confirmed subsequently at cardiac catheterization and angiography. Cine MRI and color Doppler flow mapping when used together provide high-resolution detail about the right ventricular outflow tract and pulmonary artery band anatomy and function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517388 TI - Left ventricular diastolic function in end-stage renal disease and the impact of hemodialysis. AB - Twenty-one patients (17 men and 4 women, aged 20 to 40 years) with end-stage renal disease (creatinine clearance persistently < 5 ml/min for > 3 months) were evaluated for left ventricular (LV) diastolic function by Doppler echocardiography before and after hemodialysis. Fifteen patients were on maintenance hemodialysis (group A) and 6 were studied before and after their first hemodialysis (group B). The following indexes of LV diastolic function were studied: (1) isovolumic relaxation time; and (2) Doppler indexes from mitral inflow signal--peak early velocity, peak late velocity (atrial), deceleration of early filling phase, and deceleration time of early filling phase. LV systolic function in groups A and B (LV ejection fraction 68 +/- 6 and 77 +/- 5%, fractional shortening 0.39 +/- 0.06 and 0.46 +/- 0.05%) was normal and did not change after hemodialysis. Group A had a prolonged isovolumic relaxation time of 80 +/- 22 ms, which decreased to 57 +/- 14 ms (p < 0.005). Deceleration time decreased from 248 +/- 58 to 184 +/- 38 ms (p < 0.00005) and the deceleration slope increased from 4.3 +/- 1.8 to 5.1 +/- 1.6 m/s2 (p < 0.005) after hemodialysis. In group B, isovolumic relaxation time decreased from 87 +/- 21 to 73 +/- 15 ms (p < 0.05), deceleration time decreased from 256 +/- 43 to 185 +/- 34 ms (p < 0.05), and deceleration slope increased from 3.5 +/- 0.8 to 4.2 +/- 1.1 m/s2 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517389 TI - One-year follow-up results of "culprit" versus multivessel coronary angioplasty trial. PMID- 8517390 TI - Absence of detectable delayed elastic recoil 24 hours after percutaneous transluminal coronary angioplasty. PMID- 8517391 TI - ST-segment normalization time and ventricular arrhythmias as electrocardiographic markers of reperfusion during intravenous thrombolysis for acute myocardial infarction. PMID- 8517392 TI - Cigarette smoking and age at first acute myocardial infarction, and influence of gender and extent of smoking. PMID- 8517393 TI - Histologic characteristics of tissue excised during directional coronary atherectomy in stable and unstable angina pectoris. PMID- 8517394 TI - Comparison of patients with single, double and triple coronary arterial spasm. PMID- 8517395 TI - Alterations of coronary collateral blood flow velocity during intraaortic balloon pumping. PMID- 8517396 TI - Circadian variation of primary cardiac arrest or sudden cardiac death in patients aged 62 to 100 years (mean 82). PMID- 8517397 TI - Selective surgical ablation of the slow atrioventricular nodal pathway by posterior perinodal dissection. PMID- 8517398 TI - Increased heart rate variability after radiofrequency ablation. PMID- 8517399 TI - Effect of preexcitation on Doppler indexes of left ventricular filling. PMID- 8517400 TI - Electrophysiologic effects of E-4031, a new class III antiarrhythmic agent, in patients with supraventricular tachyarrhythmias. PMID- 8517401 TI - Beta-blocker treatment of idiopathic and ischemic dilated cardiomyopathy in patients with ejection fractions < or = 20%. PMID- 8517402 TI - Relation of balloon size to outcome after balloon mitral valvotomy with single and double cylindrical balloons. PMID- 8517403 TI - Hemodynamic prerequisites for the occurrence of diastolic mitral valve regurgitation. PMID- 8517404 TI - Short-term effectiveness of nifedipine in secondary pulmonary hypertension. PMID- 8517405 TI - Relation between body fat distribution and left ventricular mass in men without structural heart disease or systemic hypertension. PMID- 8517406 TI - Risk factors for extracranial internal or common carotid arterial disease in elderly patients. PMID- 8517407 TI - Hemodynamic changes in pulmonary circulation induced by effort in the elderly. PMID- 8517408 TI - Treatment of hyperlipidemia in heart transplant recipients with gemfibrozil +/- lovastatin. PMID- 8517409 TI - Cardiac rehabilitation after cancer therapy in children and young adults. PMID- 8517410 TI - Recognition of electrocardiographic electrode misplacements involving the ground (right leg) electrode. PMID- 8517411 TI - Noninvasive estimation of right ventricular dP/dt in patients with tricuspid valve regurgitation. PMID- 8517412 TI - Therapeutic significance of exercise-induced ST-segment elevation in patients without previous myocardial infarction. AB - Twelve patients with exercise-induced ST-segment elevation without prior myocardial infarction, electrocardiographic evidence of left ventricular hypertrophy or left bundle branch block underwent thallium-201 tomography immediately after exercise and 4 hours later. Coronary angiography and left ventriculography were performed within an average of 8 days of exercise testing. Five patients had repeat exercise thallium-201 tomography after medical therapy or revascularization. All patients had large, reversible perfusion defects (average defect size 33.5 +/- 13%), with 11 of 12 patients having a > or = 25% stress perfusion defect. In 10 patients with atherosclerotic coronary artery disease, the average stenosis of the involved vessel was 93 +/- 9% (range 70 to 100). The electrocardiographic leads with ST-segment elevation predicted the site of reversible hypoperfusion. Two patients had extensive, reversible anterior hypoperfusion due to exercise-induced spasm of minimally stenosed left anterior descending coronary arteries. Follow-up exercise testing in 5 patients showed abolition of reversible hypoperfusion and ST changes after medical therapy or revascularization. In patients without prior myocardial infarction, exercise induced ST-segment elevation signifies extensive, reversible hypoperfusion that can be abolished by revascularization in patients with critical coronary stenoses and by medical therapy in those with coronary vasospasm. PMID- 8517413 TI - Interpretation of the exercise-induced ST-segment elevation. PMID- 8517414 TI - The case of a fascinating dimple. PMID- 8517415 TI - Ergonovine testing and forearm plethysmography in cocaine-related myocardial ischemia. PMID- 8517416 TI - Influence on early outcome and restenosis of urokinase before elective coronary angioplasty. PMID- 8517417 TI - Comparison of mortality in patients treated with propafenone to those treated with a variety of antiarrhythmic drugs for supraventricular arrhythmias. PMID- 8517418 TI - Effects of rate-smoothing function during treadmill exercise testing. PMID- 8517419 TI - Design and clinical application of a low-pass input filter for the evaluation of intracardiac electrograms during radiofrequency catheter ablation. PMID- 8517420 TI - Chemoprophylaxis before transesophageal echocardiography in patients with prosthetic or bioprosthetic cardiac valves. PMID- 8517421 TI - Coronary ostial dimple (in the posterior aortic sinus) in the absence of other coronary arterial abnormalities. PMID- 8517422 TI - Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty. CARPORT and MERCATOR Study Groups. AB - Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after > or = 1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p < 0.0001), (2) type C lesion (OR 2.53; p < 0.004), (3) lesion location at a bend > 45 degrees (OR 2.34; p < 0.004), and (4) stenosis located in the middle segment of the artery dilated (OR 1.88; p < 0.03); and with the following postprocedural variable: angiographically visible dissection (OR 5.39; p < 0.0001). Multivariate logistic analysis was performed to identify variables independently correlated with the occurrence of major adverse cardiac events. The preprocedural multivariate model entered unstable angina (OR 3.77; p < 0.0003), lesions located at a bend > 45 degrees (OR 2.87; p < 0.0005), and stenosis located in the middle portion of the artery dilated (OR 1.95; p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517423 TI - Long-term outcome following successful reopening of abrupt closure after coronary angioplasty. AB - Abrupt closure after coronary angioplasty is often successfully treated by repeat dilation. Long-term follow-up, including 6-month repeat catheterization and 12 month clinical evaluation, was obtained in 1,056 patients treated with acute (n = 335) or elective (n = 721) coronary angioplasty to evaluate the long-term impact of successful reopening of abrupt closure. Abrupt closure occurred in 13.5% of patients and was successfully reopened in 58%. Adverse outcomes including restenosis, death, bypass surgery, myocardial infarction and repeat angioplasty were compared between patients with successfully treated abrupt closure and those with successful procedures (residual diameter stenosis < or = 50%) without abrupt closure. For patients with acute angioplasty, the restenosis rates (> 50% diameter stenosis at follow-up) were 64% for those with successfully treated abrupt closure versus 36% for those with successful procedures without abrupt closure (p < 0.01). In addition, subsequent myocardial infarction (12 vs 3%; p = 0.01) and repeat angioplasty (21 vs 10%; p = 0.03) were more frequent in the group with abrupt closure. For patients with elective angioplasty, restenosis was 43% in those with successfully treated abrupt closure versus 45% in those without abrupt closure (p = NS). Subsequent death and myocardial infarction were more frequent in patients with abrupt closure (death: 12 vs 3% [p < 0.01]; myocardial infarction: 13 vs 3% [p < 0.01]). Long-term adverse events are increased in patients with successfully treated abrupt closure compared to those with successful procedures without abrupt closure. PMID- 8517424 TI - Rehospitalizations after coronary revascularization among Medicare beneficiaries. AB - The rehospitalization experience of Medicare beneficiaries undergoing coronary artery bypass surgery or percutaneous transluminal coronary angioplasty in 1986 and 1987 was studied by following 53,715 patients who underwent coronary artery bypass and 28,817 patients who underwent angioplasty for 1 year using Medicare hospital claims data. The 1-year rehospitalization rate after bypass and angioplasty was 629 and 863 per 1,000, respectively, compared to a rate of 607 for the Medicare patient population in general. About 45% of rehospitalizations after bypass and two thirds after angioplasty were in categories determined by an expert panel to be possibly related to the original procedure. After angioplasty, there were 61 discharges per 1,000 for bypass surgery and 140 per 1,000 for a repeat angioplasty. Rehospitalization rates for coronary artery bypass surgery after angioplasty were significantly lower for female and black patients who underwent angioplasty. The volume of rehospitalization after revascularizations makes it an important outcome measure. Medicare administrative records provide a unique source of information on rehospitalizations and make possible the monitoring of broad trends in the frequency and outcomes of coronary revascularization. The lower rates of bypass surgery after angioplasty for black and female patients are in line with other studies and bear further investigation. PMID- 8517425 TI - Design and recruitment in the United States of a multicenter quantitative angiographic trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I). AB - The present study was designed to test the effect of pravastatin, a new, 3 hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the progression of coronary artery disease in patients with moderate hypercholesterolemia. Angiographic entry criteria included the presence of > or = 1 stenosis > or = 50% in a major epicardial coronary artery, and certification of film quality through the core angiography laboratory. Patients qualified for randomization if after diet stabilization their low density lipoprotein cholesterol concentrations were > or = 130 and < 190 mg/dl, and triglycerides were < or = 350 mg/dl. Pravastatin (40 mg) or placebo is administered once daily at bedtime. Arteriography will be repeated at the end of 3 years of treatment. The primary end point of the study is the change in absolute mean coronary artery diameter. During a 30-month recruitment period, 44,145 patients were screened, and 408 were randomized. The most frequent reason for excluding patients during the screening and dietary lead in periods was a low serum cholesterol level. A large proportion of patients with documented coronary artery disease have cholesterol concentrations that are considered to be normal or only modestly increased. Adherence to strict standards of quality control for digital analysis of angiograms ensures that baseline angiograms can be interpreted at the end of 3-year follow-up. PMID- 8517426 TI - Comparison of bisoprolol with atenolol for systemic hypertension in four population groups (young, old, black and nonblack) using ambulatory blood pressure monitoring. Bisoprolol Investigators Group. AB - The antihypertensive effects of drugs are partly determined by characteristics of the patients treated. A randomized, double-blind study used 24-hour ambulatory blood pressure (BP) monitoring to compare the effects of 2 beta blockers, bisoprolol (10 to 20 mg; n = 107) and atenolol (50 to 100 mg; n = 96), administered once daily in 4 population groups. After a 4-week placebo period, patients with an office diastolic BP between 95 and 114 mm Hg were stratified according to race and age, and were randomly assigned to treatment with bisoprolol or atenolol for 8 weeks. BP averages measured by automated monitoring for the 24-hour periods were compared between groups. In elderly patients, the reductions in both average 24-hour systolic and diastolic BP were greater with bisoprolol than with atenolol (13 +/- 3/13 +/- 1 mm Hg [n = 23] vs 4 +/- 2/6 +/- 1 mm Hg [n = 30]; p < 0.01). Similarly, bisoprolol produced greater reductions in average 24-hour diastolic BP than did atenolol in nonblack patients (16 +/- 2/12 +/- 1 mm Hg [n = 85] vs 12 +/- 2/9 +/- 1 mm Hg [n = 83]; p = 0.02). Bisoprolol and atenolol were similar in the black (10 +/- 5/9 +/- 3 mm Hg [n = 22] and 10 +/ 6/6 +/- 3 mm Hg [n = 13], respectively) and young (15 +/- 1/11 +/- 1 mm Hg [n = 84] and 16 +/- 2/10 +/- 1 mm Hg [n = 66], respectively) groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517429 TI - Blood pressure 24-hour pattern in two industrialized countries (Italy and Japan) with a different culture in salt intake. AB - This study investigates the blood pressure (BP) 24-hour pattern in representative samples of 2 industrialized countries, Italy and Japan, showing different cultures in salt intake. BP was monitored by means of a noninvasive ambulatory device whose readings were analyzed by means of chronobiometric procedures. The results show that the 24-hour BP pattern is not substantially different in Italian and Japanese subjects. In particular, the expected lower BP in the Italians was not detected despite their lower salt intake. Because the 24-hour mean BP value was seen not to be proportional to salt intake, the hypothesis is formulated that maintenance of the pressure regimen within a given range of variability is a principle of human physiology. To comply with this rule the Japanese people are supposed to have ethnically developed a certain resistance to dietary salt for which their cardiovascular apparatus is protected (phyletic escape to dietary sodium excess). PMID- 8517428 TI - Effects of enalapril on the hyperinsulinemic response to severe salt restriction in obese young men with mild systemic hypertension. AB - Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity. Very low salt diets may exacerbate hyperinsulinemia, perhaps by activating the renin-angiotensin system. Therefore, the effects of a low salt diet alone and with enalapril on blood pressure and the insulin response to an oral glucose tolerance test were studied in 9 obese (body mass index 35 +/- 2 kg/m2) men with mild hypertension. Measurements were first obtained after a 2 week high-salt (20 mEq/day sodium diet+eleven 1 g salt tablets per day) baseline period. The same measurements were repeated after 2 weeks on a low salt diet (20 mEq/day) and after 2 weeks on low salt diet with enalapril in random sequence. The insulin area under the curve increased from 12.8 +/- 3.0 mU-min/dl during high salt to 16.6 +/- 3.2 mU-min/dl (p < 0.001). Plasma renin activity also increased with salt restriction from 1.4 +/- 0.2 to 3.0 +/- 0.5 ng/ml/hour, p = 0.01. With addition of enalapril to the low sodium chloride diet, the insulin area under the curve (14.5 +/- 2.6 mU-min/dl) was not significantly different from that during the high sodium chloride phase. Mean blood pressure in the laboratory was 105 +/- 1 mm Hg with high salt versus 99 +/- 1 mm Hg with low salt, p < 0.05. Addition of enalapril to the low-salt diet reduced mean blood pressure to 87 +/- 1 mm Hg (p < 0.01 vs low salt), largely by reducing total systemic resistance (p < 0.05). Salt restriction decreases laboratory BP while raising insulin levels in obese men with mild hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517427 TI - Effects of nadolol on hemodynamic and hemostatic responses to potential mental and physical triggers of myocardial infarction in subjects with mild systemic hypertension. AB - Although beta-adrenergic blocking agents are known to reduce the risk of myocardial infarction, the mechanism of this protective effect is not well understood. The recent demonstration that beta blockers selectively blunt the increased morning risk of myocardial infarction suggests that these agents block the pathophysiologic consequences of stressors concentrated in the morning. We determined the effect of nadolol on the hemodynamic and hemostatic responses to mental stress and isometric exertion (handgrip), 2 potential triggers of infarction. The study was conducted in 15 subjects with mild systemic hypertension, using a placebo-controlled, double-blind, crossover design. Nadolol reduced systolic pressure and heart rate after mental stress. Poststress systolic pressure was 139 +/- 4 mm Hg during therapy with nadolol versus 161 +/- 4 mm Hg during placebo administration (p < 0.05). Heart rate increased to 61 +/- 2 during nadolol therapy versus 89 +/- 5 beats/min during placebo therapy (p < 0.05). The systolic pressure increase was similar during therapy with nadolol and placebo (29 +/- 2 vs 33 +/- 2 beats/min, p = NS); however, heart rate increase was less during nadolol therapy (4 +/- 1 vs 12 +/- 4 vs beats/min, p < 0.01). The responses to handgrip and their modification during nadolol therapy were similar to those observed after mental stress. Neither platelet aggregability nor fibrinolytic potential was altered by nadolol. Thus, nadolol modified hemodynamic indexes without altering the hemostatic indexes measured. This hemodynamic effect may contribute to the decrease in morning cardiovascular events by beta adrenergic blockers and their well-documented cardioprotective effect. PMID- 8517430 TI - Predicting death from progressive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. AB - Data were retrospectively reviewed on 528 consecutive patients hospitalized for treatment of advanced heart failure (left ventricular ejection fraction 0.2 +/- 0.07) and cardiac transplant evaluation, who were stabilized with medical therapy and discharged home. Predictors of heart failure death or rehospitalization for urgent transplantation were identified using the Cox proportional-hazards model. Within 1 year, 59 patients (11%) died suddenly and 70 (13%) died of heart failure or required urgent transplantation. A serum sodium < or = 134 mEq/liter, pulmonary arterial diastolic pressure > 19 mm Hg, left ventricular diastolic dimension index > 44 mm/m2, peak oxygen consumption during exercise testing < 11 ml/kg/min and the presence of a permanent pacemaker were independent predictors of hemodynamic deterioration. In the absence of these risk factors the risk of hemodynamic deterioration within 1 year from this study was only 2%. This risk increased to > 50% in the presence of hyponatremia and any 2 additional risk factors. Thus, patients with advanced heart failure at highest risk for progressive hemodynamic deterioration can be identified from clinical variables that could aid in triaging such patients to earlier cardiac transplantation. PMID- 8517431 TI - Effects of mitral stenosis on pulmonary venous flow as measured by Doppler transesophageal echocardiography. AB - Pulmonary venous flow as assessed by transesophageal echocardiography (TEE) is influenced by changes in left atrial pressure and function. In mitral stenosis (MS), normal left atrial hemodynamics are altered because there is a prolonged decay in diastolic pressure from the left atrium to the left ventricle and atrial function may be altered because of atrial fibrillation. To assess the effect of the prolonged atrial diastolic pressure decay caused by MS on pulmonary venous flow, we studied 27 patients with MS (mitral valve range 0.7 to 2.4 cm2) by pulsed-wave Doppler TEE of the left or right upper pulmonary vein, and compared results with those of 13 normal subjects. Of the 27 subjects with MS, 61% showed a blunted systolic flow pattern and 39% showed a normal flow pattern with greater systolic to diastolic flow ratio. Patients with atrial fibrillation had a predominantly blunted pattern, whereas patients with normal sinus rhythm exhibited both blunted and normal flow patterns. Patients with MS had a lower pulmonary venous peak systolic flow velocity and a longer diastolic pressure halftime than control subjects. Pulmonary venous peak systolic flow velocity was significantly decreased in the presence of atrial fibrillation (p = 0.004). The mitral valve pressure halftime significantly correlated with pulmonary venous diastolic pressure halftime (r = 0.54; p = 0.004) mitral valve area (r = -0.46; p = 0.02). In conclusion, it was found that MS alters pulmonary venous flow patterns, showing a decreased pulmonary venous systolic flow and a prolonged diastolic flow, which may be useful in assessing the hemodynamics of MS. PMID- 8517432 TI - Results of percutaneous balloon mitral valvotomy in young adults. AB - The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p < 0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p < 0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p < 0.001), but was significant (> or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p < 0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p < 0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score > 8; group I) and pliable (score < or = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p < 0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517433 TI - Usefulness of signal-averaged electrocardiogram in idiopathic dilated cardiomyopathy for identifying patients with ventricular arrhythmias. AB - In idiopathic dilated cardiomyopathy (IDC), the relation between the signal averaged electrocardiogram and ventricular tachycardia (VT) remains unclear. In this study, conventional time domain and frequency domain analyses (2 dimensional, spectral temporal mapping and spectral turbulence analysis) of the signal-averaged electrocardiogram were performed in 64 patients with IDC. Eight patients had a history of symptomatic sustained VT and an additional 24 had nonsustained VT recorded during ambulatory electrocardiography. Conventional time domain analysis, using the 25 and 40 Hz filter, and spectral temporal mapping, detected late potentials within the terminal QRS in 8 (13%), 14 (22%) and 18 (28%) patients, respectively. Late potentials were seen more often in patients with than without VT, and in patients with sustained versus nonsustained VT, but these differences were not significant. The predictive accuracy of these techniques in detecting either form of VT were: sensitivity, 22, 25 and 31%; specificity, 97, 81 and 75%; and overall predictive value, 59, 53 and 50%, respectively. Two-dimensional frequency domain analysis of the signal-averaged electrocardiogram revealed a higher energy and area ratio in patients with than without VT (entire QRS), and in patients with sustained versus nonsustained VT (entire QRS and terminal QRS). Spectral turbulence analysis was abnormal in 24 patients (39%), but no differences were observed between patients with and without VT. During follow-up (mean duration 18 +/- 14 months), 5 patients had arrhythmic events (3 died suddenly, 1 had aborted sudden death and 1 developed sustained VT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517434 TI - Prognostic value of ischemia during Holter monitoring and exercise testing after acute myocardial infarction. AB - Exercise testing is generally accepted for prognostic assessment of patients after infarction, but the prognostic value of transient myocardial ischemia during ambulatory electrocardiographic monitoring remains controversial. Of 281 consecutive postinfarction patients, 173 patients (132 men, 41 women) were prospectively studied with 24-hour Holter monitoring 14 +/- 5 days after acute myocardial infarction, and with submaximal exercise testing after 15 +/- 7 days. Patients with either conduction disturbances or pacemaker rhythm and 71 patients with digitalis medication were excluded. Myocardial ischemia was defined as horizontal or descending ST depressions or transient ST elevations > or = 0.1 mV with or without angina pectoris. The follow-up period was 1 year. Myocardial ischemia was observed in 40 patients (23%) during Holter monitoring, and 96% of the episodes were asymptomatic. Ischemia occurred during exercise testing in 46 patients (27%), two thirds of whom had no symptoms. Ischemia was detected by both methods (group A) in 19 patients (11%), with exercise testing only (group B) in 27 patients (16%), and with Holter monitoring only (group C) in 21 patients (12%). In 106 patients (61%), ischemia could not be ascertained at all. The 4 groups were comparable with regard to sex and age distribution, coronary risk factors, and medication. During follow-up, 50 patients (29%) experienced clinical cardiac events: 6 patients died, 7 had recurrent myocardial infarction, 14 developed unstable angina pectoris and required immediate revascularization, and 23 patients had recurrent but stable angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517435 TI - Double-inlet ventricle in Chinese patients. AB - This study was performed to elucidate the anatomic features of double-inlet ventricle in the Chinese population. The echocardiograms of 60 Chinese patients diagnosed as having double-inlet ventricle were reviewed and analyzed. Both atria were connected to a dominant right ventricle in 36 patients (60%), to a dominant left ventricle in 17 (28%) and to an indeterminate ventricle in 7 (12%). Right atrial isomerism was present in 30 patients (83%) with double-inlet right ventricle, in 5 (29%) with double-inlet left ventricle, and in 6 (86%) with double-inlet indeterminate ventricle. Right atrial isomerism was more frequently associated with double-inlet right and indeterminate ventricles (p < 0.01; chi square). Common atrioventricular valve was frequently present in both double inlet right and indeterminate ventricles. Double-outlet main chamber was the predominant type of ventriculoarterial connection in double-inlet right and indeterminate ventricles. Total anomalous pulmonary venous connection was found exclusively in 9 patients with right atrial isomerism (5 with double inlet right and 4 with double-inlet indeterminate ventricles). In contrast to other reports, this series found double-inlet right ventricle to be the predominant type of double-inlet ventricle. This discrepancy may be due to a greater prevalence of right atrial isomerism that is usually associated with double-inlet right ventricle in Chinese patients. PMID- 8517436 TI - Right and left ventricular area and function determined by two-dimensional echocardiography in adults with the Eisenmenger syndrome from a variety of congenital anomalies. AB - The Eisenmenger syndrome has been associated with right ventricular (RV) enlargement and systolic dysfunction. However, little attention has been directed toward potentially characteristic changes in left ventricular (LV) dimensions or function. Therefore, 2-dimensional echocardiography (short-axis-papillary muscle level) was performed in 24 adults (mean age 33 +/- 7 years) with Eisenmenger syndrome to evaluate RV and LV size and function. A significant correlation was found between RV and LV end-diastolic areas (r = 0.96; regression slope 1.06), and fractional area change (r = 0.88; regression slope 1.03) in patients with a nonrestrictive ventricular septal defect (VSD) (n = 15). In contrast, in patients with Eisenmenger syndrome but no VSD (n = 9), RV and LV end-diastolic areas (r = 0.68; regression slope 0.10), and fractional area change (r = 0.08; regression slope -0.09) were discordant. RV function was preserved in most patients with a VSD, and mean RV fractional area change was significantly greater than in those without a VSD (0.50 +/- 0.13 vs 0.18 +/- 0.08; p < 0.001). No significant difference was apparent in these 2 groups (patients with and without a VSD) with respect to age, pulmonary artery systolic pressure, partial arterial oxygen pressure or hematocrit. Thus, the results indicate a relation between biventricular chamber dimensions and systolic function that is dependent on the nature and locus of the primary intracardiac defect responsible for the Eisenmenger syndrome. PMID- 8517437 TI - Effects of digoxin and enalapril on heart period variability and response to head up tilt in normal subjects. AB - To test the effects of digitalis and angiotensin-converting enzyme inhibition on the RR interval variability in an electrocardiogram, 20 normal subjects were given digoxin 0.25 mg, enalapril 10 mg, and placebo twice daily in a randomized, double-blind, crossover study. Continuous 24-hour electrocardiographic recordings obtained on day 5 of each treatment were analyzed and several time domain and power spectral measures of heart period variability were calculated. Digoxin markedly increased (up to 51%) indexes of vagal modulation of heart period without changing mean RR interval. Enalapril did not change any measure of heart period variability despite a modest hypotensive effect. To determine the effect of each treatment on the response to orthostatic stress, 10 subjects also underwent 15 minutes of 60 degrees head-up tilt; power spectra were calculated for 15 minutes at 0 degree and at 60 degrees of tilt. Neither active treatment affected the response to head-up tilt. PMID- 8517438 TI - The pharmacoeconomist--an emerging specialist in health care institutions. PMID- 8517439 TI - Army creates pharmacoeconomic center. PMID- 8517440 TI - New policies of APhA address payment reform, HIV infection, patient compliance. PMID- 8517442 TI - Program trains highly educated emigres as pharmacy technicians. PMID- 8517441 TI - Accreditation Manual for Hospitals slims down and shifts focus. PMID- 8517443 TI - Joint Commission dialogue. Standards development. PMID- 8517444 TI - New accreditation process model for 1994 and beyond. PMID- 8517445 TI - Promoting a staff member to a management position. PMID- 8517446 TI - Shifting workload to match staffing. PMID- 8517447 TI - Extension of expiration time for lorazepam injection at room temperature. PMID- 8517448 TI - Idarubicin hydrochloride turbidity versus incompatibility. PMID- 8517449 TI - Computerized database for residency and fellowship programs. PMID- 8517450 TI - Unconventional medicine. PMID- 8517452 TI - MEDWatch: the new FDA medical products reporting program. PMID- 8517451 TI - Our friendship with Edward Spease. PMID- 8517453 TI - Planning for pharmaceutical care. AB - The process for planning a pharmaceutical care practice model at the University of California-San Diego Medical Center (UCSDMC) is described. Pharmaceutical care is viewed as a health care need, analogous to medical care or dental care. Provision of such care requires that pharmacists have a generalist, rather than specialist, orientation and be held responsible for the outcomes of drug therapy. The scope of pharmaceutical care encompasses all treatment settings, emphasizing continuity of care from one setting to another. Its goal is to address the total pharmaceutical care needs of all patients. A pharmaceutical care task force was appointed to develop an overall plan for the implementation of the pharmaceutical care concept at UCSDMC. Several key practice elements were identified that served as the basis for the practice model. A three-week pilot study demonstrated the feasibility of implementing a pharmaceutical care program. An implementation plan was then developed. The program is currently being implemented. A long-range plan for implementing a pharmaceutical care practice model was developed through introspection, consensus building, and redirection of professional efforts. PMID- 8517454 TI - Development of a pharmaceutical care system in a neonatal intensive care satellite pharmacy. AB - The development of a pharmaceutical care system for a neonatal intensive care unit satellite pharmacy from existing integrated clinical, distributive, and quality assurance activities is described. Components of practice already in place included pharmacotherapeutic monitoring, evaluations for childhood immunizations, monthly medication summaries, and daily follow-up on scheduled doses returned in the unit dose exchange carts. Pharmacists documented patient drug therapy consultations on a standard form. New elements of practice emphasized organization of patients' clinical data by problem, development of specific outcome-oriented standards of care for common neonatal conditions and disease states, and quality improvement activities that evaluated the appropriateness of patient monitoring and patient outcomes. Written standards of care for specific disease states improved clinical decision-making, documentation of pharmacists' performance, and communication about patient care with other health care professionals. Elements of pharmacy practice already in place may provide a good foundation for a structured pharmaceutical care system. PMID- 8517455 TI - Multicenter evaluation of ondansetron use in hospitalized oncology patients. AB - An evaluation of ondansetron use in oncology patients in three hospitals is described. Criteria for the use of ondansetron were developed and approved by each hospital's pharmacy and therapeutics committee or medical staff executive committee. Ondansetron use was concurrently monitored in adult inpatients for four months. Nursing and physician notes were reviewed, and the patients were interviewed. Data were collected on patient demographics, medical history, dosage of ondansetron, outcome, adverse effects, and concurrent medications. The approved criteria were used to evaluate the appropriateness, effectiveness, and safety of ondansetron therapy. A total of 262 oncology patients were evaluated. Of these, 223 (85%) received ondansetron appropriately based on the emetic potential of their antineoplastic drug regimen. Ondansetron was correctly prescribed for acute-phase prophylaxis of nausea and vomiting in 252 patients (96%). Only 117 (45%) of the patients met the criterion for appropriate dosage. The mean +/- S.D. dose of ondansetron was 11.7 +/- 3.22 mg, and the mean +/- S.D. number of doses received per patient was 4.4 +/- 3.23. Of the 135 patients who received an inappropriate dosage, 106 (79%) were given a dose larger than currently recommended by the manufacturer. Positive outcomes, defined as no more than two episodes of vomiting, no more than two episodes of retching, and no more than two p.r.n. doses of antiemetics, were observed in 97%, 99.6%, and 94% of the 248 patients included in the outcome analysis, respectively. Chemotherapy was completed on schedule in all the patients, and there were no complications due to excessive vomiting or retching. Adverse reactions were reported by 21 patients (8%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517456 TI - Comprehensive program for handling hazardous drugs. AB - Development and implementation of a comprehensive program for safe handling of hazardous drugs is described. A comprehensive, multidisciplinary program for handling hazardous drugs was developed at a 1000-bed tertiary care, university teaching institution. Hazardous drugs were identified by a hazardous-drug working group consisting of occupational health professionals, pharmacists, and an industrial hygienist. The Occupational Safety and Health Administration (OSHA) 1986 handling guidelines were used as a template, with input solicited from pharmacy staff and from other institutions. A new system for receiving, storing, and transporting hazardous drugs--which also included new labeling for such drugs -was implemented. The new guidelines were discussed with the staff, with emphasis placed on absolute compliance and incorporation of the guidelines into standard operating procedures and daily pharmacy practices. All pharmacy employees underwent retraining to ensure complete understanding. A voluntary medical surveillance program for pharmacy employees was developed concomitantly to monitor exposure to genotoxic hazardous drugs. Implementation of a comprehensive program for safe handling of hazardous drugs increased employee understanding of the need for such a program and improved the hospital's compliance with recent OSHA regulations. PMID- 8517457 TI - Sources of regulatory information for pharmacists. AB - Sources of regulatory information of use to pharmacists are summarized. Regulatory information is provided by government, legal, pharmaceutical industry, nongovernment, and investigational drug sources. Databases and trade and professional organizations also provide such information. Information on legislative statutes and regulations can be found in the Federal Register, Code of Federal Regulations, and List of CFR Sections Affected. Many other government reports are also available. Various law reports are published by state and federal courts; legal textbooks, journals, and newsletters also provide pharmacy law information. Pharmaceutical industry sources supply information on U.S. drug approvals, pharmaceutical companies, and FDA enforcement actions, whereas nongovernment regulatory sources provide comprehensive regulatory and drug information. Investigational drug sources enable pharmacists to keep abreast of new drug development. Databases provide a wide variety of information, and trade newsletters supply information of interest to the organization. Knowledge of appropriate references will allow pharmacists to keep abreast of regulations that may affect them and new developments in their area of expertise. PMID- 8517458 TI - Staff pharmacists' opinions about performance appraisals. AB - Staff pharmacists' knowledge of the performance appraisal (PA) process at their hospitals and their satisfaction with the process were studied. A two-page questionnaire was mailed to staff pharmacists at 11 hospitals located around the country, and a pharmacy administrator at each hospital was interviewed. A total of 142 staff pharmacist surveys were returned. Staff pharmacists' responses about the PA process were then compared with the responses given by their pharmacy administrator. Comparison of responses showed a low percentage of agreement for many items. When process measures were compared with satisfaction scores, the results indicated that staff pharmacists are more satisfied with the PA process when a written performance plan is used and when they receive feedback about their performance throughout the year. Managers should orient staff pharmacists to the PA process that will be used to evaluate them. Written plans for improving performance and frequent feedback about performance may increase staff pharmacists' satisfaction with the PA process. PMID- 8517459 TI - Stability of fluconazole in injectable solutions. AB - The stability of fluconazole 1 mg/mL in several injectable solutions at 25 degrees C over 72 hours was studied. Fluconazole 2 mg/mL was mixed in a 1:1 ratio with 5% dextrose injection, lactated Ringer's injection, potassium chloride 20 meq/L in 5% dextrose injection, heparin sodium 100 units/mL in 5% dextrose injection, theophylline 0.8 mg/mL in 5% dextrose injection, and morphine sulfate 0.5 mg/mL in 5% dextrose injection. Three 1-mL samples were taken from each admixture at 0, 6, 12, 24, 36, 48, and 72 hours and analyzed for fluconazole concentration by stability-indicating gas chromatography. Fluconazole 2 mg/mL was stable in potassium chloride plus 5% dextrose injection and in theophylline plus 5% dextrose injection for 72 hours. Fluconazole was stable in the other injectable solutions for 24 hours. The stability of theophylline, heparin, or morphine sulfate in the presence of fluconazole was not studied. Fluconazole was stable in potassium chloride 20 meq/L plus 5% dextrose injection and in theophylline 0.8 mg/mL plus 5% dextrose injection for 72 hours and stable in the other injectable solutions for 24 hours. PMID- 8517460 TI - Planning and implementing a microcomputer local-area network. AB - Factors to be considered in planning and implementing a microcomputer local-area network (LAN) in a pharmacy department are discussed. Reasons for implementing a LAN include the ability to share data, programs, and peripheral devices among multiple users. The network operating system may be full featured or a peer-to peer system. Full-featured networks require a dedicated file server but are more powerful and versatile. The file server, if used, is the most important piece of equipment. Factors that affect the choice of a file server are the processor, the bus, memory and speed, the supplier, and the power supply. It is necessary to select network adapters and wiring and to decide whether any of the department's current computer equipment will be used in the network. Decisions must also be made about software. The equipment should be set up by the computer services department or a vendor. Two or more pharmacists must be appointed and trained as supervisors to manage the network, diagnose and correct problems, perform network backup, and guard against computer viruses. Security is a major concern because of the need for confidentiality, the licensure of software for only a limited number of users, and the risk of inadvertent alteration or erasure of data. Network users must be trained to use the system properly. Department managers should consider the need to access the LAN from computers outside the department and the possible incorporation of the LAN into a wide-area network. A microcomputer LAN can provide valuable information services, but careful planning is necessary to avoid pitfalls and to ensure that the network meets current and future needs. PMID- 8517461 TI - Managing the implementation of a pharmacy information system. AB - The stages by which a pharmacy information system should be implemented are described. Implementation can be divided into three stages. The first stage is preimplementation, during which the hardware vendor installs and configures the operating system, the software is installed, the site is prepared, files are built, policies and procedures are modified or written, staff members are trained, functions or programs are tested, and supplies are purchased. The second stage is implementation, in which the new system becomes operational and is expanded. There are four basic implementation strategies: abrupt switchover, parallel conversion, conversion of one location at a time, and conversion of functions or modules in stages. The final stage is postimplementation, which consists of testing of the system, acceptance or rejection of the system, and the institution of quality control procedures. The acceptance criteria should be developed before the system is purchased. It is important to involve the pharmacy staff and other hospital departments in the planning for an information system. Careful management before, during, and after the implementation of a new pharmacy information system is essential to a smooth and timely conversion. PMID- 8517462 TI - Noncompliance with guidelines for intravascular use of lower-osmolality contrast media. PMID- 8517463 TI - Stability of fluconazole in commonly used intravenous antibiotic solutions. PMID- 8517464 TI - Visual compatibility of gallium nitrate with selected drugs during simulated Y site injection. PMID- 8517465 TI - Selecting infusion devices. PMID- 8517466 TI - Silence: the resounding experience. PMID- 8517467 TI - Psychotherapy with the borderline patient: an introduction. AB - This paper serves as an introduction and orientation to six articles written by renowned experts on psychotherapy with borderline patients: Adler, Meissner, Chessick, Giovacchini, Kernberg, and Stone. Because the articles focus most explicitly on treatment and only touch on diagnosis, a brief excursion into diagnosis is provided. A section on conceptual framework for psychotherapy is presented, helping the reader to place the different authors' approaches into a continuum of exploratory psychotherapy. Finally brief summaries of this six articles are offered. PMID- 8517468 TI - Treatment of patients in the borderline spectrum: an overview. AB - My purpose here has been to provide no more than a brief overview of an approach to the therapy of borderline patients in the framework of a spectrum view of this complex pathology. While the perspective, generated within a tripartite framework of alliance, transference, and countertransference, allows the therapist a sense of orientation and direction in pursuing the therapeutic work with these patients, it can provide little more than guidelines, a theoretical context for thinking about the therapeutic vicissitudes that challenge and frustrate all of us. Within this perspective, I would emphasize the importance of flexibility. The complexity of therapeutic interactions and the wide scope of variation, seen not only in the borderline spectrum itself but in individual patients, calls for an unusual degree of flexibility and therapeutic adaptability to the immediate demands of the ongoing therapeutic interaction. If therapists, as they are being buffeted about by the storms and unsuspected undercurrents of the therapeutic ocean, can at least keep their bearings and know when they are being pulled out of their therapeutic role and function, their ability to deal with and help their patients will be immeasurably enhanced. I would hope that these few guidelines would provide a workable compass for the task. PMID- 8517469 TI - The psychotherapy of core borderline psychopathology. AB - A psychodynamic formulation of borderline psychopathology includes the understanding of the borderline patient's aloneness problems, need-fear dilemma issues, and difficulties with primitive guilt. The aloneness problems are at the core of the disorder, and involve an inability to maintain an evocative memory, and holding and soothing introjects of significant people when under stress of separation. The possible childhood origins of these difficulties are explored and related to the ways these issues emerge in psychotherapy. The psychodynamic formulation is crucial in the psychotherapeutic approach to the aloneness problems. It helps the therapist work with the aloneness difficulties and understand the options as the therapy continues. Since rapid therapeutic decisions are often necessary with borderline patients, the formulation provides the necessary framework, and helps the therapist process and utilize countertransference feelings. Projective identification is an important concept that helps explain the complex transference/countertransference experiences, and is used in defining the resolution of the aloneness problems of borderline patients. Finally, limit-setting and the use of transitional objects are explored, utilizing the psychodynamic framework that has been defined. PMID- 8517470 TI - The outpatient psychotherapy of the borderline patient. AB - This paper discussed common problems in the outpatient psychotherapy of borderline patients, especially their rage, seductiveness, and abrupt negative shifts. The definition of "borderline" is not settled. Even DSM-III-R mixes it up with other personality disorders. There are no pathognomonic symptoms, no specific personality constellations, and no compelling evidence for a definitive stage in infant development when this disorder is fixed; all stages are involved, from faulty foundational to oedipal periods. It is a descriptive diagnosis and typical presentations of such patients are reviewed. In the psychotherapeutic approach, limits must be set first, but these must be flexible and reasonable. Medications are used rarely and with care. We attempt to form an alliance by (a) getting the patient to join us in a study of himself or herself, especially a study of when rage and maladaptive behavior emerges, and (b) providing a consistent and reasonable ambience. The ultimate aim is uncovering and interpreting when the patient is ready for it, more and more approximating psychoanalytic treatment as the patient's pathology permits. The special phenomena of the self-object (Kohut), transitional object (Modell), and disruptive extreme erotic or raging (Kernberg) transferences were reviewed, as well as the pitfalls of therapist anxiety and impatience in dealing with them. While archaic transferences predominate, we serve as an auxiliary microscopic ego and appeal to the rational adult part of the patient's ego in a phenomenological investigation. We interpret early only if we cannot get the patient to examine what has led to the explosions and when distortions or projection without insight continues to predominate. The dangers of early transference interpretations are discussed. Therapy is long, tedious, and requires the willingness to patiently catalyze the patient's resumed development and endure the periodic disruptions. Countertransference problems and what to do about them are reviewed. PMID- 8517471 TI - Treatment issues with borderline patients and the psychosomatic focus. AB - I have discussed a group of borderline patients who can be conceptualized as having defects in character structure. There is no smooth, hierarchically arranged continuum from lower id-oriented to higher ego, secondary-process organized psychic levels. They suffer from psychic discontinuity, characterized by psychic lacunae, empty spaces devoid of psychological content. These lacunae are often the locus of somatic disruptions, a psychosomatic focus, which are manifested as psychosomatic symptoms. Though the treatment of these patients can be stormy, and, in some instances impossible, providing a setting in which these patients can comfortably regress and eventually get in touch with split-off parts of the self can lead to a manageable therapeutic interaction. On occasion, this might be life-saving. PMID- 8517472 TI - Suicidal behavior in borderline patients: diagnosis and psychotherapeutic considerations. AB - This paper summarizes the experiences with suicidal and parasuicidal behavior of the psychotherapy research project on borderline patients in progress at the Westchester Division of the New York Hospital-Cornell Medical Center. In the diagnostic evaluation of these patients, it is important to differentiate acute and chronic suicidal behavior with the presence or absence of depression. The dominant psychodynamic features of chronic characterological suicidal behavior are reviewed, with a particular emphasis on the psychopathology of self-directed and projected primitive hatred, and the defenses against its conscious awareness on the part of the patient. A general psychotherapeutic strategy to deal with suicidal and self-destructive behavior is mapped out, centered upon the transformation of self-destructiveness into specific transference constellations that must be diagnosed, interpreted, and gradually worked through in the transference in the course of the treatment. The treatment of chronic, characterologically anchored suicidal behavior without depression requires the setting up of specific structuring of the psychotherapy from the very beginning of treatment, embodied in the establishment of a treatment contract that contributes to the organizing frame for the entire psychotherapy. The precondition for this psychotherapeutic work and limiting factors affecting its effectiveness are spelled out. PMID- 8517473 TI - Paradoxes in the management of suicidality in borderline patients. AB - The risk of completed suicide in DSM-III borderline patients (BPD) equals that of manic-depressive patients. But BPD patients are also notorious for making manipulative suicide threats and gestures--"false positives" that do not foretell of imminent danger of death. BPD patients will often engage in deceitful, paradoxical behavior, attempting to make a fool of the therapist (often seen transferentially as a disparaged parent on whom the patients seeks revenge) either by escalating to serious suicidality, if a threat is not adequately heeded, or by angry criticism, if the therapist insisted on hospitalizing (as though such intervention were quite unnecessary). To deal effectively with such paradoxical behavior, therapists need to develop ever better "risk-thermostats" (in effect, "street smarts") for parrying the patients' thrusts: when to go out of one's way to be helpful, when to put responsibility on these patients, when to hospitalize, etc. There are no convenient algorithms to simplify the task. The ultimate choice of intervention shares aspects with chaos theory and weather prediction, and is sensitively dependent on initial conditions and on the idiosyncrasies and peculiarities of each member of the therapist-patient dyad. A number of general guidelines are offered in the paper, along with several illustrative cases. PMID- 8517474 TI - Group therapy with WWII ex-POW's: long-term posttraumatic adjustment in a geriatric population. AB - In this assessment of group therapy with WWII ex-POWs, the small cohort limits generalizations; however, we offer a longitudinal perspective on group process. Posttraumatic suppression and denial of emotions appears to be adaptive for time limited periods but is not a long-term solution. More lasting changes in self esteem and social interaction may be partially achieved through a supportive group environment that fosters cognitive synthesis and reorganization. PMID- 8517475 TI - The integrative focus: coordinating symptom- and person-oriented perspectives in therapy. AB - The issue of choosing between a symptomatic and a personal emphasis in psychotherapy has always been one of the major bones of contention between adherents of different approaches in the field. As it becomes increasingly clear that none of the major schools will achieve supremacy, the drive to incorporate whatever is best in any orientation becomes more pronounced. Therapists often find that the therapeutic alliance may be damaged if they neglect either their patients' symptomatic complaints or pressing developmental tasks. The integrative focus is an attempt to coordinate these two elements in therapy so that they may enhance each other instead of competing with each other. The focus is so designed as to help unify the treatment, increase motivation for therapy, and register deeply in the patient's mind. Though only a technical aid, the integrative focus may show one of the ways by which integration does not diffuse, but rather steadies and enriches the therapeutic beam. PMID- 8517476 TI - The bereaved therapist and her patients. AB - Discussions on the role of self-disclosure during times of personal crisis have been mostly confined to the theoretical. Little clinical material has been published. For the writer, this lack contributed further to the sense of loneliness following bereavement, and to uncertainty in terms of how to provide adequate information to patients while protecting herself at a time of great vulnerability. Using case vignettes, the impact of a therapist's bereavement on patients treated in an outpatient consultation-liaison service is explored. Four patients are described--one woman and two men with very serious physical conditions bringing their own frailty and death very near, and one woman with a psychophysiological condition as part of a borderline personality disorder. The impact of personal crisis is discussed, in an attempt to review how such a situation should be handled, and particularly whether and how patients should be informed. PMID- 8517477 TI - The pregnant supervisor. PMID- 8517478 TI - Epidemic cholera in the Amazon: the challenge of preventing death. AB - Epidemic cholera struck Peru in January 1991, and spread rapidly. The national cholera case-fatality rate (CFR) was less than 1% in the first six months of the epidemic, but in some rural areas, the CFR exceeded 10%. We investigated cholera mortality in the rural Amazon region, an area with a CFR of 6.3%. We conducted a case-control study, comparing 29 decedents with 61 survivors of recent cholera like diarrheal illness in 12 villages with a combined CFR of 13.5%. Of 29 decedents, 28 (96%) died in the village or en route to a health facility. Death occurred within 36 hours of illness onset for 83% of the decedents. In 11 (92%) villages, the first or second recognized case was fatal. Death was associated with receiving treatment only at home (odds ratio indeterminate; 95% confidence interval 3.5, indeterminate). Treatment with oral rehydration salts (ORS) was not protective against death for patients who received treatment only at home. Treatment with homemade sugar-salt solution (SSS) was also not protective; fewer than one-third of respondents knew the correct SSS recipe. Most decedents experienced multiple barriers to health care. Cholera victims died rapidly and early in village outbreaks, and few patients had access to health care. Provision of threatened villages with ORS supplies and education in their use before cholera strikes is essential to reducing cholera mortality in this region. PMID- 8517479 TI - Gestational malaria: assessment of its consequences on fetal growth. AB - In a region of Africa (Nord-Kivu, Zaire) where malaria is endemic, circulating malaria parasites, malaria-associated placental lesions, and a low hemoglobin level (< 10 g/dl) were observed, either singly or in combination, in 73.1% of women (n = 461) delivering at the maternity hospital. These pathologic findings were associated with low birthweight in 18.1% of the newborns, whereas the prevalence of low birthweight was 6.4% among cases without these findings (P < 0.05). Parasitemia was observed in 17.4% of all mothers and was associated with a significant decrease in birthweight. Malaria-associated lesions were found in 52.5% of all placentas and were associated with a decrease in birthweight, head circumference, and ponderal index of the newborns. Such lesions were more frequently observed among primiparae (60.5%) than among multiparae (49.5%; P < 0.05). Lastly, a low hemoglobin level, found in 38.6% of the mothers, was associated with a decrease in birthweight, length, and head circumference. The differences in the physical effects associated with each of the pathologic conditions suggest that parasitemia, placental lesions, and anemia result in acute, subacute, and chronic impairment of fetal growth, respectively. Moreover, their deleterious effects may be cumulative, since the most dramatically affected physical patterns were found when the pathologic findings were associated in the same patient. Frequent antenatal monitoring of maternal hemoglobin and parasitemia, accompanied, when necessary, with curative treatments, may help to reduce the prevalence of intrauterine growth retardation and its procession of perinatal complications. PMID- 8517480 TI - Hepatic capillariasis: first case report in the Republic of Korea. AB - We report a case of massive hepatic infection by Capillaria hepatica in a 14 month-old girl who presented with the symptom triad of persistent fever, hepatomegaly, and leukocytosis with eosinophilia. Twenty-five cases of human infection with this parasite, mostly in children, have been reported in the literature. This is the first case of hepatic capillariasis reported in the Republic of Korea. The diagnosis was made by needle biopsy of the liver. Scanning electron microscopic examination of the biopsy specimen was also performed. Thiabendazole therapy was initiated and the patient developed liver disease related IgA nephropathy during the therapy. The literature dealing with proven cases of infection with C. hepatica is briefly reviewed. PMID- 8517481 TI - A primate model for severe human malaria with cerebral involvement: Plasmodium coatneyi-infected Macaca fuscata. AB - To develop an animal model for severe human malaria, we carried out clinical and pathologic observations of Japanese monkeys (Macaca fuscata) infected with Plasmodium coatneyi. Two monkeys, eight and nine months of age, were used in this experiment. After inoculation with the parasite, both monkeys developed a fulminating acute infection with high parasitemia (20-28.2%) and became moribund with typical signs of severe malaria. In the splenectomized Japanese monkey, sequestered infected erythrocytes blocked brain capillaries. Electron microscopic studies on brain tissues revealed electron-dense knobs protruding from the membrane of infected erythrocytes that formed focal junctions with the cerebral capillary endothelial cells. These findings were remarkably similar to those seen in human cases. Prominent sequestration of the infected erythrocytes was uniformly distributed in capillaries of the lungs and heart. The nonsplenectomized Japanese monkey developed acute anemia with a packed cell volume of 6%, but blockage of brain capillaries was minimal. However, sequestered, infected erythrocytes were evident in capillaries of the heart and lungs of this animal. Our study showed that the Japanese monkey is highly susceptible to P. coatneyi infection and that this system provides a model for the study of severe human malaria. PMID- 8517482 TI - Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes. AB - The inflammatory infiltrates in the heart lesions of chronic chagasic cardiomyopathy are composed predominantly of small lymphocytes with admixed macrophages, plasma cells, and segmented leukocytes. The phenotypes of the lymphoid cells in these infiltrates of human Chagas' disease have not been previously detailed. We used a panel of monoclonal and polyclonal antibodies to immunohistochemically characterize the inflammatory cells in frozen and fixed cardiac tissues from autopsied patients with severe chronic chagasic cardiomyopathy. In all cases, the inflammatory lesions were dominated by CD8+ lymphocytes, many of which expressed granzyme A. A few macrophage-like cells that expressed tumor necrosis factor-alpha were observed in each case. Relatively few natural killer cells or B lymphocytes were found in the lesions. These findings in human chagasic lesions are compatible with concepts that involve cytolysis and fibrosis, and new experimental findings that emphasize potential roles for CD8+ T cells in Chagas' disease. PMID- 8517483 TI - Reversal of chloroquine resistance in murine malaria parasites by prostaglandin derivatives. AB - An oligomeric ester of prostaglandin B2 (OC-5186) was found to reverse chloroquine resistance in the murine malarial parasite Plasmodium berghei. When mice were infected with either chloroquine-sensitive or -resistant P. berghei on day 0 (by intraperitoneal injection of 1 x 10(6) parasitized erythrocytes), they died before day 23. When treated with 15 mg/kg/day of chloroquine for the first four days of infection, all mice infected with the sensitive-strain survived, while all those infected with the resistant strain died before day 23. When OC 5186 (3-12 mg/kg/day) was administered in combination with chloroquine for the first four days, 60% of the animals infected with the resistant strain survived. The differences in the survival rate between the group treated with chloroquine only and the group treated with a combination of drugs (chloroquine plus 3-12 mg/kg/day of OC-5186) were significant. There was also a significant inhibition of parasitemia in the group treated with the combination of drugs. The combinations of chloroquine and a monomer ester of prostaglandin B2 (OC-5181) had some antimalarial activity, but the differences between the chloroquine-treated group and the combination treatment group were not significant in terms of both the parasitemia and the survival rate. Another oligomeric ester of prostaglandin E1 (MR-356) as well as unesterified monomer prostaglandins (PGA2 and PGB2) were ineffective by themselves and in combination with chloroquine. PMID- 8517484 TI - Concurrent parasitic infections in onchocerciasis and the occurrence of adverse reactions after ivermectin treatment. AB - Ivermectin is a safe, effective, and relatively well-tolerated drug for the treatment of human onchocerciasis. However, due to side effects of the drug, large-scale ivermectin distribution without medical supervision is not recommended. The mechanisms involved in the pathogenesis of ivermectin-induced adverse reactions are not yet known. Since onchocerciasis patients are likely to have concurrent parasitic infections, we investigated whether side effects that occur after ivermectin treatment could be related to the presence of parasite eggs and cysts in stool samples prior to treatment. One hundred twenty-nine onchocerciasis patients were treated with a single dose of ivermectin (150 micrograms/kg) and side effects were graded according to the classification of Greene and others. Stool samples were collected before and three days after treatment. A high percentage (80.5%) of the patients reported adverse effects (57% mild, 14.1% moderate, and 9.4% severe reactions). Most (95.1%) of the patients had one or more concurrent parasitic infections. No relationship could be found between the occurrence and extent of side effects and the severity of concurrent intestinal parasitic infections. However, side effects were significantly correlated with pretreatment microfilarial counts. Ivermectin treatment did not induce significant short-term changes in Trichuris trichiura or Schistosoma mansoni egg counts. However, a significant reduction in Ascaris lumbricoides egg counts and Entamoeba coli cyst loads was observed; a cure rate of 46% for cysts was reached. In contrast, hookworm egg production increased after ivermectin treatment. Further studies are required to verify ivermectin induced changes in cyst and hookworm loads as well as the significance of these findings. PMID- 8517485 TI - Isolation of Batai virus (Bunyaviridae:Bunyavirus) from the blood of suspected malaria patients in Sudan. AB - From August through November 1988, 77,500 patients with fever presented to the municipal hospital and to eight government health centers in Kassala, a town of approximately 400,000 individuals in eastern Sudan. A diagnosis of malaria, based primarily on clinical presentation, was made in 14,395 individuals during this four-month period; fevers of unknown origin were diagnosed in 29 patients. A Bunyavirus that was antigenically similar or identical to Batai virus by complement fixation and plaque-reduction neutralization tests was recovered from two of 196 sera collected from patients with acute fever admitted to the municipal hospital in Kassala in October 1988. IgM antibody against this virus was detected by enzyme-linked immunosorbent assay in 7% of the sera from patients with acute fever tested and IgG antibody was detected in 61%. PMID- 8517486 TI - Trends of human immunodeficiency virus type-1 infection in female prostitutes and males diagnosed with a sexually transmitted disease in Djibouti, east Africa. AB - A cross-sectional serosurvey for human immunodeficiency virus type 1 (HIV-1) was conducted during the first quarter of 1991 among high risk groups in Djibouti, East Africa, and compared with previous surveys in 1987, 1988, and 1990. The survey demonstrated evidence of HIV-1 infection in 36.0% (n = 292) of street prostitutes, 15.3% (n = 360) of prostitutes working as bar hostesses, and 10.4% (n = 193) of males diagnosed with a sexually transmitted disease. By multivariate modeling, HIV-1 seropositivity in prostitutes was associated with Ethiopian nationality, working as a street prostitute, and residing in Djibouti for two years or less. We suggest that prostitution, particularly street prostitution, is a major route of HIV-1 transmission in Djibouti. PMID- 8517487 TI - Characteristics of the acquired immunodeficiency syndrome in Brazil. AB - The clinical and epidemiologic characteristics of the acquired immunodeficiency syndrome (AIDS) were studied in a tropical area of Brazil. During an 18-month period (July 1989-January 1991), 111 consecutive AIDS patients (102 men and nine women) were evaluated. Patients reported homosexual/bisexual activities (60%), intravenous drug use (19%), or both (6%), heterosexual activities (11%), blood transfusions (2%), and 2% belonged to an undetermined category. Weight loss, fever, oral thrush, and diarrhea were present in > or = 70% of the patients at presentation. An unexpected high frequency of hepatomegaly (49%) was detected, and found to be significantly associated with tuberculosis (P < 0.0001). Although the epidemiologic features of human immunodeficiency virus transmission were comparable to the United States/European pattern, the clinical spectrum of opportunistic infections more closely resembled that reported in Africa and Haiti, with a greater frequency of fungal and mycobacterial infections than Pneumocystis carinii pneumonia and viral infections. PMID- 8517488 TI - Diversionary role of hoofed game in the transmission of Lyme disease spirochetes. AB - To determine whether the presence of ungulates may inhibit transmission of the agent of Lyme disease (Borrelia burgdorferi) while promoting the abundance of its European vector tick (Ixodes ricinus), we compared the feeding density of subadult ticks on roe deer (Capreolus capreolus), red deer (Cervus elaphus), fallow deer (Dama dama), and wild sheep (Ovis ammon) near Berlin and in Brandenburg State, Germany. The prevalence of spirochetal infection in these ticks was compared with that in ticks swept from nearby vegetation. Spirochetes are present in nearly one-fifth of nonfed, questing nymphal and adult wood ticks in the region. Many ungulates in this intensely enzootic region fail to mount a detectable humoral response against the agent of Lyme disease, even when exposed to numerous infected ticks. During the height of the summer, each ungulate may support the feeding of hundreds of subadult ticks. Larvae feed lower on the bodies of hoofed game than do nymphs. Few ticks retain infection by the Lyme disease spirochete after feeding on hoofed game animals. We conclude that numerous I. ricinus ticks feed on ungulates, but that such host-contact fails to infect these ticks while eliminating pre-existing spirochetal infection. PMID- 8517489 TI - High human malarial infectivity to laboratory-bred Anopheles gambiae in a village in Burkina Faso. AB - The malarial infectivity of an African village population was tested by selecting a demographically representative sample of individuals for study, regardless of parasitemia or gametocytemia. The infectivity of this population people to laboratory-bred mosquitoes was investigated using membrane feeding techniques. Tests on 322 subjects (greater than four years of age) indicated that approximately 48.4% were capable of infecting mosquitoes. There were similar proportions of infectious individuals among gametocyte carriers (52.5%) and nongametocyte carriers (46.6%). All age groups appeared to contribute equally to this infective reservoir. Most of the infections resulted in low oocyst loads (1.8 oocysts) on the midgut of the positive mosquitoes and only a few mosquitoes per batch were infected (11.5%). A previous entomologic survey estimated 90 infected bites/person/year and a low parity index in Anopheles gambiae (< 60%) as well as in An. funestus (< 40%), the two main malaria vectors in this region. This low parity index could indicate a low life expectancy for infected mosquitoes and could therefore explain an inoculation rare lower than expected considering the high degree of infectivity of the human population studied. PMID- 8517490 TI - Molecular karyotype characterization of Leishmania panamensis, Leishmania mexicana, and Leishmania major-like parasites: agents of cutaneous leishmaniasis in Ecuador. AB - Molecular karyotypes of Leishmania isolates from patients with cutaneous leishmaniasis in Ecuador were analyzed by pulsed-field gel electrophoresis (PFGE) and Southern blot hybridization. The DNA karyotypes of L. major-like parasites were similar between two human isolates from a lowland coastal and a highland Andean region, but were apparently different from those of eleven World Health Organization reference strains including L. major. The smallest chromosome of 240 kilobases in L. major-like parasites was found to belong to the 715-class of small linear chromosomal DNAs, which have been shown to appear in some lines of Leishmania. Chromosome banding patterns of L. mexicana isolates exhibited a novel, ordered, chromosomal ladder, and were identical among four human isolates and one canine isolate from a restricted geographic region in the Andes. On the other hand, minor chromosome size polymorphisms were observed among three L. panamensis isolates from different endemic regions near the Pacific Coast. Chromosomal locations of dihydrofolate reductase-thymidylate synthetase and P glycoprotein genes revealed further differences in chromosomal organizations among these Leishmania species in Ecuador. These results indicate that karyotype analysis by PFGE is useful for epidemiologic studies of leishmaniasis in Ecuador. PMID- 8517492 TI - West Nile virus (Flaviviridae:Flavivirus) in experimentally infected Argas ticks (Acari:Argasidae). AB - To better define the possible role of argasid ticks in the epidemiology of West Nile virus, adult Argas arboreus, A. persicus, and A. hermanni were fed through a membrane on fetal bovine serum containing 10(5.5) 50% tissue culture infective doses (TCID50)/ml of West Nile virus. The virus was detected for three and four days after feeding in A. persicus and A. hermanni, respectively. The virus titers then decreased to undetectable levels in both species. When the infective dose was increased to 10(6.2), virus was detected until days 6 and 8, respectively. In A. arboreus, virus titers in whole tick homogenates reached a peak of 10(4.0) on day 4 postfeeding and remained constant at 10(3.0) after day 6 throughout the 20- or 50-day observation periods. Virus was detected by isolation, indirect fluorescent antibody, and histochemical techniques in the salivary glands, ovaries, synganglia, and coxal fluids. Infected ticks successfully transmitted virus to clean chickens on day 20 postfeeding. No evidence of transstadial transmission from nymph to adult was detected. Larvae from experimentally infected females successfully transmitted virus to clean chicks and virus was recovered from F1 larvae. Venereal transmission was not detected. Virus was present in coxal fluids secreted by infected females after infective meals. This study demonstrates West Nile virus infection in experimentally infected A. arboreus ticks and documents horizontal and vertical transmission in this species. PMID- 8517491 TI - Strongyloides stercoralis: an initial autoinfective burst amplifies primary infection. AB - Compartmental analysis of Strongloides stercoralis burdens in experimentally infected, serially necropsied dogs was used to test an autoinfective burst hypothesis. The hypothesis states that in well-established, active infections and in chronic infections as well, the rate of larval development is down-regulated so that most larvae do not attain infectivity internally. The majority pass in the feces as preinfective, rhabditiform larvae, but a few (those with the most rapid developmental rate) attain infectivity internally, and therefore are positioned for autoinfectivity. In contrast, in immunologically naive hosts, larval development proceeds without host hindrance and many larvae, proceeding at the most rapid rate of a spectrum of normal intrinsic developmental rates, attain infectivity internally. For a brief period, hyperinfection occurs, during which the adult worm population increases sharply. Gut-level resistance soon occurs, larval development is retarded, and an increasing proportion of larvae are discharged as preinfective rhabditiform larvae. With fewer larvae developing to infectivity internally, recruitment into the adult population decreases, with an attendant increase in the mean age and a gradual decrease in the size of the adult population. The data and the attendant model strongly support this autoinfective burst hypothesis. PMID- 8517493 TI - Cutaneous sarcoidosis and foreign bodies. AB - A histopathological diagnosis of sarcoidosis is, by convention, one of exclusion and is reached only when other potential causes of granulomatous disease, such as foreign bodies, are eliminated. We report herein three cases of systemic sarcoidosis with cutaneous manifestations of the disease, in which polarizable foreign particles were associated with the granulomata in the skin. We submit (a) that a granulomatous foreign body reaction and sarcoidosis are not mutually exclusive, (b) that particulate foreign matter may actually serve as a nidus for granuloma formation in sarcoidosis, and (c) that the occasional presence of extraneous material within the granulomata of sarcoidosis requires greater recognition by pathologists. PMID- 8517494 TI - Nevus with cyst. A report of 93 cases. AB - Nevus with cyst is characterized by a melanocytic nevus that is closely associated anatomically with an epidermoid cyst. We describe the clinicopathologic manifestations of 93 cases (from 92 individuals) observed during a 6-year period and review the features of the 69 previously reported nevi with cysts in the world literature. It is important for both clinicians and pathologists to recognize this common benign condition because growth of these lesions is frequently misinterpreted by the patient as representing either a new melanoma or malignant transformation of a preexisting lesion. Variants of nevus with cyst include lesions in which the nevus is a congenital, "dysplastic," blue, or Spitz nevus. The cysts may be steatocystomas, hidrocystomas, dermoid, or trichilemmal cysts. In some cases, folliculitis may be present within the nevus instead of a true cyst. PMID- 8517495 TI - Bulge-activation hypothesis: is it valid? AB - This essay is a critique of a revolutionary hypothesis, and of the language used to frame it, that offers a novel interpretation for the dynamics of the follicular cycle by distinguishing, distinctly, germinative cells in the bulge from matrical cells in the bulb. Curiously, this intriguing "bulge-activation hypothesis" elicited practically no response in the scientific literature, and our critique is designed to rectify that. PMID- 8517496 TI - Tripartite differentiation (squamous, glandular, and melanocytic) of a primary cutaneous neuroendocrine carcinoma. An immunocytochemical and ultrastructural study. AB - We report a case of primary cutaneous neuroendocrine carcinoma (PCNEC) with squamous, glandular, and melanocytic differentiation and associated Bowen disease. The paranuclear globular positivity of low-molecular-weight cytokeratins agrees with the ultrastructural observations of paranuclear fibrous bodies in the small neuroendocrine cells, while the diffuse cytoplasmic positivity corresponds to the sparse intermediate filaments in large cells with squamous differentiation. "Transitional forms" are characterized by both diffuse and globular cytoplasmic positivity for cytokeratins and by the ultrastructural evidence of neuroendocrine and squamous features. Therefore the ultrastructural demonstration of intracytoplasmic tonofibrils and tonofilaments, intercellular glandular lumina, lined by well-formed microvilli, and immature premelanosomes in the neurosecretory cells supports the proposed tripartite differentiation of neuroendocrine cells of this case of PCNEC. PMID- 8517497 TI - Infundibulocystic basal cell carcinoma. AB - A case of infundibulocystic basal cell carcinoma is reported. The patient was a 56-year-old Japanese woman. Clinically, the cutaneous lesion was a 2 x 4-mm, dark reddish, well-demarcated papule on the left nasal bridge. Histologically, it showed findings typical of the disease criteria described by Walsh and Ackerman, i.e., it was a well-circumscribed, superficially located, basaloid cell tumor with multiple cysts containing cornified cells lined by infundibular epithelium. It showed no follicular bulbs and papillae, and the stroma was not highly fibrocytic, although clefts within the connective tissues and abundant mucin were observed. The tumor was diagnosed as an infundibulocystic basal cell carcinoma. PMID- 8517498 TI - Multiple miliary osteomas of the face. AB - We report an exceptional case of multiple miliary osteomas of the face in an elderly woman, which developed in the absence of previous inflammatory or neoplastic skin disease. Excellent aesthetic results were achieved by surgical removal of about 90 miniature stones present in the facial skin of the patient. PMID- 8517499 TI - Cutaneous epithelioid hemangioendothelioma without systemic involvement. AB - Epithelioid hemangioendothelioma (EH) is a unique vascular tumor characterized histologically by epithelioid endothelial cells. A case of EH arising from the dermis and presenting as a nodule of the palm is described. To our knowledge, this is the third report of a cutaneous presentation of EH and the first report of a patient with this rare neoplasm with solitary cutaneous involvement. A review of the literature is also presented. PMID- 8517500 TI - Folliculosebaceous cystic hamartoma. Reported case with a neural component. AB - The clinical and histological features of a recently recognized entity, folliculosebaceous cystic hamartoma, are reported. The peculiarity of our case is a previously unreported neural proliferation in the stroma. PMID- 8517501 TI - Acantholytic acanthoma. AB - In 1988, Brownstein described a previously unrecognized benign acanthoma, the acantholytic acanthoma. We report an additional case seen on the arm of a 61-year old man. PMID- 8517502 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 7. PMID- 8517503 TI - Substance abuse in anaesthetic staff: the kraken wakes. PMID- 8517504 TI - Chemical dependence in anaesthetic registrars in Australia and New Zealand. AB - The Supervisors of Anaesthetic Training in Australia and New Zealand were surveyed and asked to report any cases of chemical dependence from anaesthetic registrars at their hospital from 1981 to 1991. From 83 questionnaires there were 65 (78%) returned. There were 14 departments (22%) with experience of one or more cases during this interval. Only five (7%) reported conducting a lecture or tutorial on the problem. The departmental reports covered 4425 registrar years of training and there were 17 cases reported. Of these, 13 were complete and are considered in detail. It is estimated that 1.3% of those who entered anaesthetic training during the interval were recognised to become chemically dependent during their training. Follow-up was available on only six of the 13 registrars and only one was reported to have completed training. The results of this survey indicate that chemical dependence is already a major health problem amongst anaesthetic registrars in Australia and New Zealand. PMID- 8517505 TI - Red cell, plasma and albumin transfusion decision triggers. AB - Hypothetical clinical cases were used to investigate transfusion-related decision making. Three red cell, three fresh frozen plasma (FFP) and three albumin transfusion decision cases were administered by questionnaire to 228 medical staff. The transfusion decision triggers were identified and comparisons made between resident and specialist groups and between Melbourne and Sydney participants. Factors important in red cell transfusion decisions included haemoglobin, symptoms of anaemia, presence of co-morbidities or surgery, gender, period of hospitalisation and the degree of documented blood loss. FFP administration was influenced by an abnormal coagulation test, the presence of co morbidities and by the number of red cell units transfused. The administration of albumin, concentrated or 5% SPPS, was influenced by the period of hospitalisation and clinical circumstances such as a falling urine output postoperatively, and by the presence of hypotensive complications. Different transfusion responses were noted: resident staff transfused red cells and FFP earlier than specialists; Sydney specialists were more conservative of red cell transfusion; Melbourne specialists more conservative of FFP administration and surgeons were four times more likely to transfuse patients than physicians or anesthetists at certain haemoglobin values. PMID- 8517506 TI - Anaesthesia for laparoscopic general surgery. AB - Laparoscopic surgery minimises postoperative morbidity. Patient benefits include reduction in postoperative pain, better cosmetic result and quicker return to normal activities. Hospital stay is shortened resulting in a reduction in overall medical cost. The intraoperative requirements of laparoscopic surgery however can lead to serious physiological changes and complications. While there is a low but definite perioperative mortality rate associated with minor gynaecologic laparoscopic procedures, laparoscopic general surgical procedures are performed on older patients and patients with acute surgical conditions and are likely to be associated with a higher incidence of perioperative complications. The major problems during laparoscopic surgery are related to the cardiopulmonary effects of pneumoperitoneum, systemic carbon dioxide absorption, extraperitoneal gas insufflation, venous gas embolism and unintentional injuries to intra-abdominal structures. An appraisal of the potential problems is essential for optimal anaesthetic care of patients undergoing laparoscopic surgery. Appropriate anaesthetic techniques and monitoring facilitate surgery and allow early detection and reduction of complications. The need for rapid recovery and short hospital stay impose additional demands on the anaesthetist for skillful practice. PMID- 8517507 TI - Aminoglycoside volume of distribution and illness severity in critically ill septic patients. AB - The volume of distribution of amikacin and the APACHE II score were determined in 42 critically ill patients being treated for a gram-negative infection. The mean volume of distribution (Vdt) was 0.41 +/- 0.12 l/kg with a wide range (normal of 0.25 l/kg). There was a good relationship between the Vdt and illness severity as measured by the APACHE II score (r = 0.70; P < 0.001). Critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels. The aminoglycoside Vdt may be useful in determining the degree of capillary leak and tissue oedema that accompanies sepsis. PMID- 8517508 TI - Background infusion with patient-controlled analgesia: effect on postoperative oxyhaemoglobin saturation and pain control. AB - The aim of this study was to determine whether the addition of a background infusion (BI) to patient-controlled analgesia (PCA) would lead to significantly improved pain control or poorer oxyhaemoglobin saturation (SpO2) after gynaecological surgery. Sixty-two patients were studied for 24 hours postoperatively; pain scores and morphine dose were recorded hourly, SpO2 was recorded every 10 seconds. Administration of the BI resulted in a significant increase in total morphine dose received although there was no difference in the severity of postoperative desaturation between the therapies. Despite the increased morphine dose pain scores also were similar in the two groups. Addition of a BI at 1 mg/hr did not confer any advantage over PCA alone and is not recommended when PCA is used in this patient group. PMID- 8517510 TI - High-dose adrenaline in adult in-hospital asystolic cardiopulmonary resuscitation: a double-blind randomised trial. AB - Forty intensive care unit patients requiring cardiopulmonary resuscitation were randomised to receive either the standard dose of adrenaline (1 mg every five minutes) or high-dose adrenaline (10 mg every five minutes). In the majority of patients, overwhelming sepsis was the major contributing factor leading to cardiac arrest. In this group of patients no difference could be detected in response to high-dose adrenaline compared with the standard dose. Although no side-effects were noted with this high dose of adrenaline, more investigation is required prior to its routine use in cardiopulmonary resuscitation. PMID- 8517509 TI - Cognitive function during moderate hypoxaemia. AB - The effect of hypoxaemia (mean SpO2 78%) on cognitive function was measured in two groups of twelve normal subjects. A series of psychometric tests was administered to each subject in the same sequence and consisted of the Reitan trail-making test, a digit symbol substitution test, a visuospatial orientation test and the simple unprepared reaction-time test. Psychomotor performance was assessed in a double-blind manner while the subjects were breathing first air and then either air or a hypoxic mixture. While there was improvement in time for the trail-making test during a repeat study breathing air, there was significant deterioration of time to completion of the test in conditions of hypoxia. A significant learning effect in the orientation test was seen in the control group but this did not occur in hypoxic subjects. Hypoxaemia was shown to cause a significant impairment of simple unprepared reaction time compared with controls. All the changes in cognitive function were small and there were no subjective differences in the air or hypoxic groups. The usefulness of the Reitan trail making and the simple unprepared reaction-time test in the assessment of psychomotor performance deficit under conditions of hypoxaemia has been demonstrated by this study in normal subjects. It was concluded that a mean oxygen saturation of 78% caused only minor changes in cognitive function in normal subjects. PMID- 8517511 TI - Delayed onset of alcuronium effect in children with cyanotic congenital heart disease. AB - The effect of alcuronium dichloride (0.3 mg/kg) was studied in seven normal children (Group A), nine with acyanotic congenital heart disease (Group B) and eight with cyanotic disease (Group C). The onset of action was recorded using an integrated electromyograph and blood samples taken for later estimation of plasma concentrations of the drug. The mean time (SD) taken to 75% suppression of twitch height was 1.3(0.8), 1.7(1.0) and 3.8(2.8) minutes, respectively, in each of the three groups. This was significantly slower in Group C compared with both other groups (P < 0.05). While six of the Group A patients and seven from Group B reached 95% paralysis within ten minutes, only two of the cyanosed children achieved this level of relaxation. However, if times to 95% relaxation were extrapolated, there was no significant difference between the groups at 4.5(3.9), 5.8(5.7) and 10.9(6.5) minutes respectively. There was a weak but statistically significant relationship between haematocrit and time to 75% blockade. Maximum twitch depression was similar in all three groups with plasma concentrations at this time being 1.6(0.7), 1.8(0.5) and 2.3(1.4) micrograms/ml respectively. Again, there was no statistically significant difference between these values. These results confirm that the clinical onset of relaxation is delayed in children with cyanotic congenital heart disease, possibly because of delayed distribution of alcuronium. PMID- 8517513 TI - Laboratory evaluation of the Go Medical PCI: a disposable patient-controlled analgesia device. AB - A low-cost, disposable patient-controlled analgesia device was tested using a computer-controlled, automated testing station designed to simulate clinical use. Five devices were tested and delivered a mean bolus dose size of 95% of nominal, although one device achieved only 85% of nominal. Delivery was lowest immediately following an eight-hour interval during which no demands were made. Further development and evaluation of this interesting device is warranted. PMID- 8517512 TI - Analgesia following arthroscopic knee surgery. A controlled study of intra articular morphine, bupivacaine or both combined. AB - In a double-blind, randomised controlled trial, we studied 40 patients who received one of four intra-articular injections at the end of arthroscopic surgery. Each group contained ten patients. The patients in Group 1 received normal saline 25 ml; those in Group 2 received bupivacaine 0.25% 25 ml; those in Group 3 received morphine 5 mg in normal saline 25 ml; and those in Group 4 received a combination of bupivacaine 0.5% 12.5 ml and 5 mg of morphine made up to 25 ml with normal saline to produce the same bupivacaine concentration as Group 2. At the time the patient awoke, and 30min, 1hr, 1hr 30min, 2hr, 4hr, 8hr, 12hr, and 24hr postoperatively, pain was assessed using a visual analogue scale. The need for supplementary analgesic agents in the first 24 hours was recorded. All pain scores were significantly lower (P < 0.05) in Groups 2, 3 and 4 compared with the control group with the exception of Group 2 at 24 hours. Pain scores were significantly lower (P < 0.05) for Group 2 compared with Group 3 for the first 90 minutes postoperatively. At 4, 8, 12 and 24 hours postoperatively the pain scores were significantly lower (P < 0.05%) for Group 3 compared with Group 2. Group 4 had the lowest pain scores over the recorded period compared with the other groups. The need for supplemental analgesia was significantly lower (P < 0.05) in the treatment Groups 2, 3 and 4 compared to the control Group 1. There was no significant difference in supplemental analgesic requirements between Groups 2, 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517514 TI - An alarm for monitoring CPAP. AB - We have built a device for use within the hospital and at home that is designed to warn of circuit disconnection when used in conjunction with continuous positive airway pressure (CPAP) therapy delivered via ventilators or CPAP generating systems. The Royal Children's Hospital CPAP alarm is a compact, battery operated alarm and monitor of circuit pressure. The device includes intrinsic safety features including a safety blow-off valve, a high pressure alarm and design features that make the device practical, safe and easy to use by both trained hospital personnel and home care attendants with limited training. PMID- 8517515 TI - Anaphylactoid reaction to Syntocinon. PMID- 8517516 TI - Kawasaki disease and anaesthesia. PMID- 8517517 TI - Transient increase of parasympathetic tone in patients with cervical spinal cord trauma. PMID- 8517518 TI - Continuous intrathecal analgesia with opioid/local anaesthetic mixture for cancer pain. PMID- 8517519 TI - Displacement of a Celestin tube: an unusual cause of difficult intubation. PMID- 8517520 TI - The laryngeal mask airway--the first ten years. PMID- 8517521 TI - The Geoffrey Kaye Oration. Adelaide AGM, 1992-October 19th. PMID- 8517522 TI - Minilaparotomy under local infiltration in a high risk case. PMID- 8517523 TI - An unusual problem with an endotracheal tube. PMID- 8517524 TI - An unusual and lethal tracheal foreign body. PMID- 8517525 TI - Portex epidural minipack. PMID- 8517526 TI - The laryngeal mask airway--an unusual complication. PMID- 8517527 TI - The laryngeal mask--another insertion technique. PMID- 8517528 TI - Analgesia for ESWL. PMID- 8517529 TI - The CIG Medishield "Bassoon" active scavenging interface. PMID- 8517530 TI - Diathermy interference with syringe pump function. PMID- 8517531 TI - Oral premedication with methadone, promethazine and diclofenac. PMID- 8517532 TI - Thigh tourniquet a trigger for MH? PMID- 8517533 TI - Aspirin and breast feeding. PMID- 8517534 TI - Anaesthesia and breast feeding. PMID- 8517535 TI - Jugular venous oximetry. PMID- 8517536 TI - Imperforate nasogastric tube. PMID- 8517537 TI - Malfunction of Servo ventilator and auto-PEEP. PMID- 8517538 TI - Pressure transducer cable fault. PMID- 8517539 TI - Predicting difficulty of laryngoscopy. PMID- 8517540 TI - Awake endobronchial intubation. PMID- 8517541 TI - Medical involvement in the recovery room. PMID- 8517542 TI - Near-infrared spectrophotometric monitoring of stroke-related changes in the protein and lipid composition of whole gerbil brains. AB - Strokes are a critical problem in the U.S. that affect more than 500,000 people annually. Research into the causes of stroke and testing of drug therapies to reduce ischemic and postischemic damage to the brain is frustrated by an inability to continuously follow the physical and chemical events that occur during ischemia and reperfusion in vivo. Near-IR spectrometry is used in this paper to observe stroke-induced changes in the lipids and proteins of whole brain samples and in intact subjects. The examination of whole brains is made possible by a combination of hardware and software techniques designed to make the sample presentation to the spectrometer more reproducible. Near-IR spectrophotometry of brain tissue discriminates between adult (3-4 months of age) and aged (18-20 months of age) brains as well as between brains exposed to 5- and 10-min ischemia. The near-IR analytical method has many applications in aging and stroke research, including the noninvasive determination of age from brain spectra obtained transcranially, simultaneous multicomponent analysis of lipids and proteins, and quantification of edema. PMID- 8517543 TI - Affinity electrophoresis in multisectional polyacrylamide slab gels is a useful and convenient technique for measuring binding constants of aryl sulfonamides to bovine carbonic anhydrase B. AB - This paper describes convenient preparations of heterogeneous multisectional polyacrylamide slab gels and the protocols that use these gels to measure protein ligand binding constants [using bovine carbonic anhydrase B (CAB) as a model system]. Unlike procedures for affinity electrophoresis using tube gels, all binding information concerning protein-ligand interactions was encoded in a single multisectional gel: the procedure involving for measuring binding constants required no postelectrophoresis manipulation of gels. Use of these types of gels improves the accuracy of affinity gel electrophoresis (AGE) by providing reliable internal protein standards. Binding constants measured by AGE agree with those determined in homogeneous solution by spectrophotometric measurements. This technique has been used to investigate the influence of the length of the spacer separating the ligand and the polyacrylamide backbone on the binding constants. Dissociation constants obtained using the affinity gels approach the values measured in free solution, when the spacer is sufficiently long (> or = 18 A); affinity ligands having short spacers give high apparent dissociation constants. PMID- 8517544 TI - Rapid purification of double-stranded DNA by triple-helix-mediated affinity capture. AB - A simple and rapid method for the preparation of highly pure plasmid DNA has been developed. The DNA is directly captured from bacterial cell lysates by formation of a triple-helical structure between the plasmid dsDNA and a 20-base biotinylated oligonucleotide attached to streptavidin-coated magnetic beads and then eluted from the beads in pH 9 buffer solution. No phenol extraction, ethanol precipitation, RNase digestion, or CsCl gradient centrifugation is required. A general purpose cloning vector, pHJ19, was constructed for this application from pUC19 DNA by insertion of a 40-base sequence suitable for triple-helix formation. The approach was also found suitable for the purification of lambda bacteriophage DNA. PMID- 8517545 TI - Rapid extraction and structural characterization of biomolecules in agarose gels by laser desorption Fourier transform mass spectrometry. AB - A method originally developed for the extraction of biomolecules from agarose gel slices has been utilized as a rapid means of isolating biological compounds from gels for subsequent structural characterization by matrix-assisted last desorption-ionization Fourier transform mass spectrometry (MALDI/FTMS). This "freeze-squeeze" extraction method involves pressure extrusion of fluid from frozen gel slices and provides near 50% recovery of analyte in less than 5 min. Experiments were directed at examining the recovery efficiency of the extraction method using 14C-labeled adenosine monophosphate and investigating the effect of high buffer concentrations on the laser desorption mass spectra. When coupled with this extraction technique, MALDI/FTMS can be used to detect and identify biomolecules at the low picomole level in agarose gel slices. The accurate mass measurements and MS/MS capabilities of the FTMS were exploited to provide detailed structural information at the isomeric level for oligonucleotides electrophoresed into agarose gels. PMID- 8517546 TI - Determination of thiabendazole residues in waters by solid-phase spectrofluorometry. AB - A new, sensitive and simple spectrofluorometric method for the determination of thiabendazole (TBZ) residues was studied. TBZ on Sephadex G-15 gel, pH 4.70 acetate buffer, is fixed to give fluorescence. The fluorescence of the gel-TBZ system, packed in a 1-mm quartz cell was measured directly using a solid-surface attachment. The applicable concentration range was 1.5-10.0 ng.mL-1 with a relative standard deviation of 1.4% and a detection limit of 0.1 ng.mL-1. The method was applied to the determination of thiabendazole in natural, waste, sea, and residual waters (98-100% recovery). The method is more sensitive and selective than other methods described in the literature. The presence of other fluorescent pesticides (dichlone, carbaryl, morestan, o-phenylphenol) with similar spectral features (lambda exc and lambda em neighboring to excitation and emission wavelengths of the TBZ) did not cause interference. PMID- 8517547 TI - Coated surface acoustic wave sensor employing a reversible mass-amplifying ligand substitution reaction for real-time measurement of 1,3-butadiene at low- and sub ppm concentrations. AB - Real-time measurement of 1,3-butadiene gas using a surface acoustic wave (SAW) sensor coated with the square-planar Pt(II)-olefin pi-complex PtCl2-(1-hexene) (pyridine) and related complexes is described. Amplification of the sensor response results from displacement of two 1-hexene molecules by each butadiene molecule and formation of the bridged complex [PtCl2(pyridine)]2(1,3-butadiene). Using a 30-MHz SAW oscillator, the rate of frequency change is linearly related to the butadiene air concentration from 150 ppb to > or = 13 ppm and a calculated detection limit of 101 ppb is obtained. Using a 60-MHz oscillator, the detection limit is reduced to 24 ppb. No effect on the sensor response is observed with changes in relative humidity from 5 to 80% or changes in temperature from 25 to 35 degrees C. No interference is observed from several industrially relevant non olefin organic gases and vapors. Responses are obtained for several olefins, but they interfere with the response to butadiene only at higher relative concentrations. The reagent can be regenerated repeatedly by brief exposure to 1 hexene vapor with retention of the original response characteristics upon subsequent exposure. The potential for using this sensor to monitor occupational 1,3-butadiene exposures is discussed in light of the recently proposed occupational exposure limit of 2 ppm. PMID- 8517548 TI - Assessment of metals in reconstituted metallothioneins by electrospray mass spectrometry. AB - A method has been developed that combines electrospray ionization mass spectrometry with pH control to provide analysis of metals in native or reconstituted metallothioneins. These metalloproteins cooperatively bind seven divalent metal ions, most commonly Zn2+ and Cd2+. Since the protein is denatured and metal ions are lost below pH3, the pH of the electrospray solution is critical to successful results. The metal-free apoprotein was detected with its most abundant ions in a charge state of 6+, while the folded metallothionein metal complexes were observed with lower charge states. The retention of seven metals in the molecular ions detected is consistent with the hypothesis that metallothionein retains its conformation in the gas phase. This mass spectrometric technique can be used to determine rapidly and accurately how many and what cations are incorporated per molecule of protein. Information about molar distributions and estimates of relative abundances of various complexes in the sample can be acquired in a single measurement. PMID- 8517549 TI - Optimization of capillary electrophoresis of mixtures of basic peptides and comparison with HPLC. AB - Fourteen synthetic, strongly basic hexadeca- to octadecapeptides, which differ only in one amino acid residue, were synthesized and characterized. In order to investigate the application of capillary electrophoresis for the separation of mixtures of closely related basic peptides, seven different mixtures, which represent possible byproducts during solid-phase synthesis, were analyzed by HPLC and different techniques of capillary electrophoresis. Peaks within the mixture were identified by single peak injection or on-line CE/MS. Utilization of micellar electrokinetic capillary electrophoresis offered the separation of complex mixtures. Comparing the electrophoretic mobilities with calculated correlations, we found that the separation of peptides of this length is influenced not only by the different size and charge but also by hydrophobicity and the orientation of the charge due to different conformations. PMID- 8517550 TI - Static secondary ion mass spectrometry of adsorbed proteins. AB - Static secondary ion mass spectrometry (SIMS) was used to analyze proteins adsorbed to biomaterial surfaces. A spectral interpretation protocol was established by examining homopolymers of 16 amino acids. This protocol allows for the assignment of peaks unique to the various amino acids. Static SIMS was used to analyze plasma proteins adsorbed to titanium. The various factors that contributed to the relative intensities observed in the spectra were explored. The potential application of the technique for studying protein-fouled materials was investigated by analyzing a fouled sensor membrane. PMID- 8517551 TI - HPLC-based method for determination of absolute configuration of alpha-chiral amines. AB - We introduce a novel, HPLC-based method for facile determination of the absolute configuration of alpha-chiral amines. Our method is easily applied to a variety of compounds, including amino acid derivatives. The method involves initial derivatization of the chiral amine analyte with the chiral derivatizing reagent, N-succinimidyl alpha-methoxyphenylacetate (SMPA), to produce the corresponding diastereomeric adducts. Inspection of a particular rotomer of the SMPA adduct and application of simple rules correlates absolute configuration and HPLC elution order. A key aspect of our method is that it can be used to determine absolute configuration without using enantiomeric standards of the amine analytes. Furthermore, it is of utmost significance that our method can also be used to determine absolute configuration even when only one analyte enantiomer of unknown absolute configuration is present, as is often the case for enzymatic products, naturally derived compounds, or enantiomerically enriched compounds prepared via chiral syntheses. We have observed strict adherence between predicted and observed absolute configuration for a wide variety of alpha-chiral amines. The chromatographic method we present in this paper is very practical and has several important advantages over NMR-based approaches which have been previously developed. For example, microgram quantities of an analyte in a complex enzymatic mixture can be directly analyzed by our HPLC-based method while the impurities often preclude definitive proton assignments in the NMR approach. PMID- 8517552 TI - Capacitated and acrosome reacted spermatozoa of goat (Capra indicus): a fluorescence and electron microscopic study. AB - Plasma membrane alterations accompanying in vitro capacitation and acrosome reaction of goat spermatozoa were studied using lectin labelling, scanning electron microscopy, and freeze-fracture methods. Fluorescein isothiocyanate linked lectins namely; Canavalia ensiformis (ConA), Maclura pomifera (MPA), Arachis hypogaea (PNA), Glycine max (SBA) and Triticum vulgaris (WGA) agglutinin were used to examine the distribution of surface carbohydrates during these two events. The head and the sperm tail reveal altered lectin labelling features after capacitation and acrosome reaction. After capacitation the surface coat components for MPA, SBA, and WGA are shed from the spermatozoon head. ConA receptors on the head are retained after capacitation but are partially shed in the acrosome reacted spermatozoa. SBA receptor sites appear on the sperm tail of the capacitated spermatozoa. Unusual morphological changes attending capacitation involve the sperm tail-end which develops a novel entity, which we have termed 'spatula'. The 'spatula' shows strong binding with ConA and WGA only. In the acrosome reacted spermatozoa the spatulated tail-end unwinds with a concomitant loss of lectin labelling. Highly ordered membrane particles, 'ladders' of the middle piece of the epididymal sperm tail, disappear and IMP clearings appear on the middle piece and in the spatulated ends of the capacitated spermatozoa. But in the acrosome reacted sperm IMPs reappear and are randomly disposed on the middle-piece and are clustered in small patches on the principal-piece. IMP free areas appear on the plasma membrane covering the acrosome and the outer acrosomal membrane (OAM) of the capacitated spermatozoa. The plasma membrane and OAM fuse at multiple foci and appear as acrosomal 'ghosts' which remain associated with the sperm head even after acrosome reaction. PMID- 8517553 TI - Comparison of the antigonadotropic activity of three GnRH antagonists (Nal-Glu, Antide and Cetrorelix) in a non-human primate model (Macaca fascicularis). AB - We compared the antigonadotropic activity of the GnRH antagonists Nal-Glu, Antide and Cetrorelix in a non-human primate model (Macaca fascicularis). Orchidectomized animals received a single subcutaneous injection at doses of 250 micrograms kg-1 (n = 4), 625 micrograms kg-1 (n = 4) and 1250 micrograms kg-1 (n = 3) of the compounds Nal-Glu ([Ac-D-Nal(2)1, D-4-Cl-Phe2, D-Pal3, Arg5, D Glu(AA)6, D-Ala10]-GnRH), Antide (Nal-Lys, [Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, Nic Lys5, D-Nic-Lys6, Ip-Lys8, D-Ala10]-GnRH) or Cetrorelix ([Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, D-Cit6, D-Ala10]-GnRH). Blood samples were collected before and 3, 6, 12, 24, 48, 72, and 96 h after GnRH antagonist administration. Serum was analysed for concentrations of bioactive LH and immunoactive LH and FSH. All three compounds decreased LH secretion within 3-12 h (P < 0.05) and FSH secretion within 12-48 h (P < 0.05) after injection. Major differences between the GnRH antagonists were observed with regard to the effective dose and duration of action. At a dose of 250 micrograms kg-1 Nal-Glu and Antide only transiently suppressed LH and FSH release, whereas Cetrorelix induced complete inhibition (P < 0.05) which lasted for the entire observation period. At a dose of 625 micrograms kg-1 Cetrorelix exhibited the longest duration of action and Nal-Glu the shortest. At the highest dose of 1250 micrograms kg-1 Nal-Glu, Antide and Cetrorelix markedly inhibited LH and FSH secretion throughout the entire study period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517554 TI - Analysis of human sperm membrane antigens reacting with sera from antisperm antibody positive and negative patients by western blotting. AB - Immunological infertility is thought to be caused by the binding of antibodies to 'fertility-related' antigen(s) on the sperm membrane. We compared antibody profiles in sera from 20 ASA(+) and ASA(-) men, using a sperm membrane extract as an antigen. Antigens were separated by SDS-PAGE under reducing conditions. The patients were classed as ASA(+) by the MAR (> 50%), d-IBT (> 20%) and TAT (> 1:64). The results showed that immunoreactive bands in both the ASA(+) and ASA(-) groups were heterogeneous and included bands covering the whole molecular weight range. Statistical analysis showed significantly more patients in the ASA(+) group having immunoreactive bands at molecular weights of 32 Kd (P = 0.006) and 79 Kd (P = 0.02) when compared to the ASA(-) group. In the ASA(-) group significantly more patients had reactive bands at 81 Kd (P = 0.01) when compared to the ASA(+) group. The 32 Kd antigen reacted only with sera from ASA(+) patients. We conclude that differences exist between the ASA(+) and ASA(-) groups when this extraction method is used and that the isolation and purification of the 32 Kd protein may justify further investigation. PMID- 8517555 TI - Comparison of resazurin test results with various sperm parameters. AB - The resazurin reduction test was performed on semen samples from 83 untreated infertile and 9 pregnancy-confirmed fertile males, and the results were compared with other sperm parameters. The highest correlations with resazurin grade were found for motile sperm concentration (r = 0.65, P < 0.001), per cent motility (r = 0.58, P < 0.01), and percentage of swollen sperm (r = 0.57, P < 0.01). There were also significant but weak correlations between resazurin grade and both sperm concentration and linearity. There was a significant difference in the rate of positive tests between samples from normozoospermic and fertile males, and samples from patients exhibiting abnormal semen parameters (P < 0.001). These findings indicate that the resazurin test may be able to predict those males who may be fertile despite an abnormal semen analysis, and therefore, the test may be useful in the evaluation of the infertile patient as a part of a comprehensive male fertility assessment. PMID- 8517556 TI - Bacterial foci in the teeth, oral cavity, and jaw--secondary effects (remote action) of bacterial colonies with respect to bacteriospermia and subfertility in males. AB - Bacteriospermia requiring medical treatment were diagnosed in more than 70% of the subfertile patients who had since 1988 attended the gynecological clinic at the RWTH hospital in Aachen. In 23% of all cases specific treatment with antibiotics did not reduce the concentrations of bacteria in sperma. Thirty-six patients with bacteriospermia resistant to antibiotic therapy were then subjected to dental examination. A high incidence of potential dental foci was found in all patients. In a test group of 18 patients these sources of potential infection were eliminated. Between dental operations and therapy swabs were taken to determine bacterial levels and bacteriological composition. It could be demonstrated that the bacterial spectrum of the intraoral samples was almost identical with the spermiograms. Six months following completion of dental treatment a further spermiogram analysis was carried out. In the test group about two thirds of the spermiograms proved sterile. Spermatological parameters, such as motility, density and morphology, had also clearly improved. In the control group the findings of the spermiogram remained poor. This study indicates that a direct causal relationship exists between bacterial colonies (dental foci) and therapy-resistant bacteriospermia which probably leads to subfertility. PMID- 8517557 TI - Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis. AB - Nimesulide, a novel non-steroidal anti-inflammatory drug, was used in cases of abacterial prostato-vesiculitis. Thirty patients with a mean age of 33.7 years (range 18-58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration-time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH-NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value +/- SD of 0.58 +/- 0.13 micrograms ml-1) and at the fourth hour for OH-NIM (2.98 +/- 0.38 micrograms ml 1). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 +/- 2.34% for NIM; 31.87 +/- 8.66% for OH-NIM. Dysuric symptoms were relieved in 20 (66%) patients. A clear amelioration of inflammatory signs were observed at transrectal ultrasound evaluation in 16 (54%) patients. No statistically significant changes of sperm count and motility in the whole sample were observed, while a significant reduction in the number of abnormal forms occurred. From these results, nimesulide appears to be an effective anti-inflammatory drug with a good diffusion into the genital apparatus and low side-effects. PMID- 8517558 TI - Report of the meeting of the German Society of Andrology, Leipzig on September 26, 1992. PMID- 8517559 TI - Clinical predictors of post-traumatic seizures in children with head trauma. AB - STUDY OBJECTIVES: To determine the clinical characteristics associated with early post-traumatic seizures in children with head trauma. DESIGN, SETTING, AND TYPE OF PARTICIPANTS: Retrospective chart review; urban trauma center/pediatric emergency department. Trauma patients aged 3 months to 15 years given discharge diagnosis ICD-9-CM codes indicating head trauma and seen from 1988 to 1990 were eligible for the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 194 patients, 96% suffered blunt trauma and 53% had a loss of consciousness. Fifty-one percent of 141 computed tomography (CT) scans of the head were abnormal, most frequently demonstrating skull fractures (34%), subdural hematomas (15%), and cerebral contusions (14%). Eighteen patients (9.3%) suffered post traumatic seizures. A loss of consciousness, a low Glasgow Coma Scale (GCS) score (3 to 8), and an abnormal CT scan were associated with post-traumatic seizures (P < .02, .001, and .02, respectively). However, only a low GCS score was predictive of post-traumatic seizures when these factors were considered simultaneously (P < .001), with 38.7% of patients with low GCS scores suffering post-traumatic seizures and 3.8% of patients with high GCS scores suffering post-traumatic seizures. In children with low GCS scores, treatment with phenytoin was associated with a decrease in post-traumatic seizures. CONCLUSION: In the pediatric head trauma patient, a GCS score of 3 to 8 appears to be predictive of post-traumatic seizures. The data from this retrospective study are consistent with the hypothesis that prophylactic phenytoin reduces post-traumatic seizures in the pediatric head trauma patient with a low GCS score. PMID- 8517560 TI - Five-year experience in prehospital intraosseous infusions in children and adults. AB - STUDY OBJECTIVE: To evaluate the ability of emergency medical technician paramedic (EMT-P) units to become and remain proficient in the performance of the intraosseous infusion procedure. DESIGN AND SETTING: Descriptive nonrandomized trial open to all patients meeting protocol criteria over a five-year period; prehospital urban and suburban area with a population of 951,000. PARTICIPANTS: One hundred fifty-two consecutive patients (age range, newborn to 102 years) who had intraosseous infusion line placement attempted by EMT-Ps. INTERVENTION: Jamshidi sternal intraosseous infusion needle placed in the proximal tibia bone marrow in patients requiring emergency vascular access for fluid and/or medication administration. RESULTS: EMT-Ps performed 165 attempts on 152 patients with a five-year success rate of 76% per patient and 70% per attempt. Success rates per patient age group were 78%, 0 to 11 months; 85%, 1 to 2 years; 67%, 3 to 9 years; and 50%, 10 years or older. Success rates were significantly higher in children 3 years old compared with children and adults 3 or more years old (P = .04). Proficiency was maintained over the five-year study period. Infiltration was the most common complication, occurring in 14 patients (12%). Errors in landmark identification and needle bending were the most frequent identifiable causes for unsuccessful attempts. Evidence of clinical response to fluid or medication infused was noted in 28 patients (24%). CONCLUSION: EMT-P units can successfully perform the intraosseous infusion line procedure in patients of all ages. Proficiency is maintained over time despite its infrequent use by individual EMT-Ps. PMID- 8517561 TI - Clinical validity of ultrasound in children with suspected appendicitis. AB - STUDY OBJECTIVE: To determine the accuracy of diagnosing appendicitis in the pediatric population by using graded compression ultrasonography. DESIGN: Retrospective case review. SETTING: University-affiliated community hospital with an emergency department census of approximately 19,000 pediatric visits per year. TYPE OF PARTICIPANTS: Ninety-eight children (age less than 13 years) with clinically suspected appendicitis who had graded compression sonographic studies during the 24-month study period. INTERVENTIONS: Medical records were reviewed for patient demographics, presenting signs and symptoms, sonographic findings, surgical results, and hospital course. Patients who did not undergo surgery were followed up by telephone for a minimum of two months. RESULTS: Ninety-eight children (42 boys and 56 girls; age range, 2 to 12 years; mean age, 8.0 years) with clinical signs and symptoms of acute appendicitis were examined sonographically. Of the 26 patients whose appendicitis was verified at surgery, ultrasound was positive in 22, with an overall sensitivity of 85%. Of the 72 patients who did not have appendicitis, ultrasound was negative in 68, with a specificity of 94%. Two patients with false-positive ultrasound went to surgery and were found to have acute ileitis and perforated Meckel's diverticulum. The overall diagnostic accuracy was 91.8% (90 of 98). CONCLUSION: Use of ultrasound to diagnose acute appendicitis was performed with a sensitivity of 85% and a specificity of 94%. This allows the same accuracy in children as has been reported with adults. PMID- 8517563 TI - The adult patient in the pediatric emergency department. AB - STUDY OBJECTIVE: To establish the frequency of use of pediatric emergency departments by adult patients and the spectrum of disease with which they present. DESIGN: Prospective, descriptive study and unblinded survey. SETTING: Children's Hospital pediatric ED. TYPE OF PARTICIPANTS: Seventy-two adult patients presenting to a pediatric ED during a two-year period and 31 pediatric emergency medicine fellowship directors. INTERVENTIONS: For each patient, we recorded demographic information, chief complaint, interventions by physicians, diagnosis, condition, and disposition after initial care. Pediatric emergency medicine fellowship training program directors were surveyed by telephone regarding their experiences with adult patients and the extent of adult emergency medicine training within their programs. MAIN RESULTS: Of the 72 adult patients evaluated, one third (22) were treated for trauma and the remaining 50 for medical illness. More than 40 different diagnoses were encountered, including stroke and myocardial infarction. Twenty patients (27.8%) required hospitalization, four (5.6%) in intensive care settings. Of the 31 fellowship directors surveyed, 27 (87.1%) indicated that adult patients had been managed in their EDs during the previous year. All but one reported that their fellowship programs incorporated between one and four months of adult emergency medicine in their curricula. CONCLUSION: Adults frequently present to pediatric EDs for both minor and serious illnesses. Training in adult emergency medicine should be a part of all pediatric emergency medicine fellowship programs. PMID- 8517562 TI - A randomized, controlled trial comparing a tissue adhesive with suturing in the repair of pediatric facial lacerations. AB - STUDY OBJECTIVE: To compare the tissue adhesive Histoacryl Blue with suturing in the repair of pediatric facial lacerations. DESIGN: Prospective, randomized controlled trial. SETTING: Emergency department of a pediatric teaching hospital. PARTICIPANTS: Eighty-one children presenting with clean facial lacerations less than 4 cm in length and 0.5 cm in width. INTERVENTIONS: Patients were allocated randomly to have their lacerations repaired with sutures or Histoacryl Blue. RESULTS: The two groups were similar for demographic and clinical characteristics. Photographs taken at three months were rated by two plastic surgeons blinded to the method of closure. There was no difference between groups for appearance scores on a visual analog scale (60.5 mm for Histoacryl Blue versus 57.2 mm for suture, P = .45) or on a categorical scale (Histoacryl Blue versus sutures: unacceptable, 11% versus 13%; acceptable, 59% versus 71%; excellent, 30% versus 16%; P = .76). Measures of observer agreement produced Pearson correlations of .72 and .94 on the visual analog scale and kappa coefficients of .46 and .73 on the categorical scale. Histoacryl Blue was assessed as less painful on a visual analog scale (24.7 versus 43.7 mm, P < .01) and faster (7.9 versus 15.6 minutes, P < .001). CONCLUSION: Histoacryl Blue is a faster and less painful method of facial laceration repair that has cosmetic results similar to the use of sutures. PMID- 8517564 TI - Reduction of anterior shoulder dislocations by scapular manipulation. AB - STUDY OBJECTIVES: This study examined the success rate, time required, technical ease, and reported patient discomfort for the use of scapular manipulation in the reduction of anterior shoulder dislocation. This study included a new variation of this technique using the seated position. DESIGN: Prospective case series over a 19-month period. SETTING: The emergency departments of a university and a community hospital. TYPE OF PARTICIPANTS: Patients with anterior shoulder dislocations. INTERVENTIONS: Emergency medicine resident and attending physicians were instructed in the technique of scapular manipulation in a classroom setting and requested to use this method initially for the reduction of anterior shoulder dislocations. Premedication was at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: There were 54 patients with 61 dislocations. Scapular manipulation was attempted by 19 residents and 12 attending physicians. The overall success rate of scapular manipulation was 79%, whereas that of physicians experienced with the technique was 86%. Of the successful reductions, 65% were performed in less than one minute, and physicians rated the technique as very easy or easy to perform in 74% of these cases. No premedication was used in 64% of the attempts at scapular manipulation, and these patients reported pain ratings similar to those of the premedicated groups. No complications were noted in this study. CONCLUSION: Scapular manipulation generally is a simple, rapid, and reliable technique for the reduction of anterior shoulder dislocation. PMID- 8517565 TI - Does nasotracheal intubation increase complications in patients with skull base fractures? AB - STUDY OBJECTIVES: To determine if the complications associated with skull base fractures are increased when nasotracheal intubation is performed in the field. DESIGN: Retrospective, case-control study over a five-year period. SETTING: A helicopter service returning to a Level I trauma center. TYPE OF PARTICIPANTS: All injured patients treated in the field who had either radiographic or clinical evidence of skull base fractures in whom nasotracheal intubation was attempted (38) compared with all patients with skull base fractures in whom nasotracheal intubation was not attempted (48) and a convenience sample of patients without skull base fractures in whom nasotracheal intubation was attempted (45). Patients with obvious midface motion on initial examination were excluded. Complications of skull base fractures were categorized as cerebral spinal fluid leak of longer than 24 hours and/or meningitis, cranial nerve injury, diabetes insipidus, and intracranial placement of the endotracheal tube. INTERVENTIONS: Blind nasotracheal intubation was performed by experienced flight nurses. RESULTS: There were no patients in whom an endotracheal tube was placed intracranially. There was no significant difference in complication rate between the two groups with skull base fractures (with nasotracheal intubation, 24%; 95% confidence interval, 11% to 40%; without nasotracheal intubation, 25%; 95% confidence interval, 14% to 40%). The group without skull base fracture had none of the complications usually associated with skull base fractures. CONCLUSION: Patients with skull base fracture have a significant complication rate (25%). The complications associated with skull base fractures are not markedly increased by attempts at nasotracheal intubation in the field. PMID- 8517566 TI - Practical selection criteria for noncontrast cranial computed tomography in patients with head trauma. AB - STUDY OBJECTIVE: To study patients with acute trauma retrospectively for clinical predictors of positive cranial computed tomography. METHODS: We reviewed the medical records and noncontrast computed tomography scans of 373 consecutive head trauma patients presenting to a trauma Level I emergency department. Potential criteria for patient selection were analyzed statistically, using both univariate and multivariate models. RESULTS: Our data suggest that relying on four variables -positive neurologic examination, intoxication, and a history of amnesia or focal neurologic deficit--as screening criteria for computed tomography would have saved 58.6% of the scans performed on these patients. Together, these criteria had a sensitivity of 90.1% and a negative predictive value of 98.1% for abnormal computed tomography. Four patients with positive scans would not have been detected using this strategy. None of these patients deteriorated clinically or required operative intervention. CONCLUSION: Our data suggest that it may be possible to effectively screen patients with head trauma for cranial computed tomography using clinical criteria and so reduce the current number of scans performed by more than half. However, a prospective study is required to confirm our results. PMID- 8517567 TI - Emergency physician workload: a time study. AB - STUDY HYPOTHESIS: Physician service time varies with patient service category, length of stay, and intensity of service. DESIGN: Prospective time study of emergency physician services. Physicians recorded the beginning and ending times of each service episode offered to a patient (whether at the bedside or occurring elsewhere in the department). Each episode was defined as an "interaction," with the total service time offered to a patient being the sum of all interactions for that patient. Length of stay was the time interval from when the patient registered in the emergency department to when the patient was released. Intensity of service was calculated as service time divided by length of stay. SETTING: University-affiliated community teaching hospital. TYPE OF PARTICIPANTS: One thousand three hundred forty-seven ED patients were entered into the study for nonselected (514), walk-in (637), observation (52), laceration repair (102), or critical care (42) services. Six of 12 physicians in the group staffing the ED participated in the study. Patient data were entered onto study cards when the service was offered. Patients were entered into the study consecutively except when the physician became too busy to see one patient at a time and accurately enter time data; such interruptions occurred for 18% of the patients. RESULTS: Physician service time for nonselected service patients (24.2 minutes per patient; 95% CI, 23.1-25.3) was consistent with ACEP's findings for nonselected services offered by emergency physicians (22 minutes per patient). Physician service time did not vary significantly from the standard for laceration repair patients (25.0 minutes per patient; 95% CI, 22.6-27.4) but did vary significantly from the standard for walk-in (9.8 minutes per patient; 95% CI, 9.3-10.3; P < .05), observation (55.6 minutes per patient; 95% CI, 50.7-60.5; P < .05), and critical care patients (31.9 minutes per patient; 95% CI, 26.2-37.6; P < .05). Walk-in and laceration repair patients had a single physician-patient interaction (1.3 per patient and 1.1 per patient, respectively), consistent with a discrete service offered during episodic care. Observation and critical care patients had multiple physician-patient interactions (6.3 per patient and 2.6 per patient, respectively) over an extended period, which is consistent with additional services being offered during their period of observation/holding. CONCLUSION: Case mix of patient services affects emergency physician workload and should be considered in planning departmental staffing needs. PMID- 8517569 TI - Cranial computed tomography in the emergency department evaluation of HIV infected patients with neurologic complaints. AB - STUDY OBJECTIVE: To demonstrate the usefulness of cranial computed tomography (CT) in the emergency department evaluation of HIV-infected patients and patients with risk factors for HIV infection who present with neurologic complaints. DESIGN: Retrospective review of imaging reports and medical records of patients who visited the ED from March 1991 through March 1992. SETTING: Urban university ED. PARTICIPANTS: Patients with HIV infection or risk factors for infection who underwent emergency cranial CT after presenting to the ED with headache, altered mental status, focal deficits, or other neurologic signs or symptoms. RESULTS: One hundred forty-six patients visited the ED 169 times. Of the 169 cranial CTs obtained, 85 (50%) were normal, 49 (29%) showed atrophy only, and 35 (21%) demonstrated focal lesions, with mass effect noted in ten (6%). Enhancing lesions were present in 13 scans. In 21 (12%) cases, CT revealed either an indication for admission, a contraindication to lumbar puncture, or both. In 25 instances, patients with lesions had nonfocal presentations and no papilledema. Two presentations--focal deficit and altered mental status--were each statistically significantly associated with lesions on CT. In seven patients with multiple ED visits, repeat CT showed new findings. Among patients who had risk factors but were of unknown HIV status, there was the same proportion of abnormal scans as in known HIV-infected patients. CONCLUSION: CT detected clinically significant neuropathology among our study patients. Because lesions and mass effect were associated with nonfocal as well as focal presentations, CT is indicated in every neurologically symptomatic patient with HIV infection or risk factors for infection. Because HIV-related diseases can progress rapidly, repeat CT is recommended even in patients with recent scans. PMID- 8517568 TI - Effect of needle changing and intravenous cannula collection on blood culture contamination rates. AB - STUDY OBJECTIVES: We tested the hypotheses that blood culture positivity and contamination rates were not increased by not changing needles between venipuncture and inoculation of blood culture bottles or by taking blood for culture by freshly inserted IV cannulae. DESIGN: A prospective study of blood cultures collected by venipuncture or IV cannulae taken from an emergency department population. Venipuncture samples were randomized into needle change (standard method) or no needle change before inoculation into blood culture bottles. PARTICIPANTS: Nine hundred forty patients requiring blood cultures after assessment in the ED. INTERVENTIONS: A standard disinfection procedure using 0.5% chlorhexidine in 70% alcohol was used. Blood was collected by venipuncture and inoculated with or without needle change. Blood collected by IV cannula was inoculated with a fresh needle applied to the collection syringe. MEASUREMENTS AND MAIN RESULTS: There was no statistically significant difference in contamination rates for blood collected by venipuncture with no needle change (6.4%) compared with needle change (4.2%, P > .30). No significant difference in contamination rates was noted for blood taken by freshly inserted IV cannulae (4.3%) compared with venipuncture with needle change after sampling (4.2%, P > .90). Some problems with randomization resulted in unequal numbers in the needle change (286) versus no-needle-change (141) subgroups, and this may have introduced bias. A higher rate of pathogen growth was observed in blood taken by IV cannula (11.4%) compared with the standard method (6.3%) (P < .025). A significantly greater rate of Gram-negative sepsis was noted in the IV cannula group (6.6%) compared with direct venipuncture with needle change (1.1%) and no needle change (4.2%, P < .01). CONCLUSION: The results of this study do not support the practice of changing needles before inoculating blood samples into blood culture bottles. Collection of blood for culture through freshly inserted IV cannulae is associated with a low contamination rate and is an acceptable alternative to direct venipuncture. Sources of bias in this study suggest that further research is needed to determine the optimal technique for collecting blood cultures. PMID- 8517570 TI - Alveolar-arterial oxygen gradients in elderly patients with suspected pulmonary embolism. AB - STUDY OBJECTIVE: To determine the usefulness of the alveolar-arterial oxygen gradient for detecting pulmonary embolism in elderly patients presenting to the emergency department. DESIGN: Retrospective cohort analysis. SETTING: Two university-affiliated community hospitals. TYPE OF PARTICIPANTS: Consecutive patients more than 64 years old who underwent pulmonary angiography for the presumed diagnosis of acute pulmonary embolism. INTERVENTIONS: Arterial blood gas samples were chosen for comparative analysis only if obtained when the pulmonary embolism first was suspected clinically (before lung scans or angiograms) and the patient was breathing room air. Predicted PaO2 and alveolar-arterial gradients were calculated for each patient. MEASUREMENT AND RESULTS: A total of 123 patients met all study criteria; mean +/- SD patient age was 74 +/- 6 years. Fifty-four patients (44%) had angiographically documented emboli. In this cohort, the mean PaO2 was 61.4 mm Hg (range, 34.3 to 83.8 mm Hg), and the mean alveolar arterial gradient was 46.6 mm Hg (range, 19 to 75 mm Hg). In three patients, the alveolar-arterial gradient was normal for their age. However, in comparison with the 69 patients with normal pulmonary angiograms, there was no significant difference in PaO2 (mean, 59.9 mm Hg) or the alveolar-arterial gradient (mean, 46.0 mm Hg). CONCLUSION: An elevated alveolar-arterial oxygen gradient is entirely nonspecific in the elderly population and is of minimal use in the diagnosis of acute pulmonary embolism. A normal alveolar-arterial gradient should not preclude further diagnostic procedures if there is a high index of suspicion. PMID- 8517572 TI - The use of tissue adhesion for traumatic laceration repair in the emergency department. AB - STUDY OBJECTIVE: To characterize the role of tissue adhesion as an adjunct in wound closure. DESIGN: Patients were subjectively selected for tissue adhesion and assessed for efficiency, pain, complications, and cost effectiveness. SETTING: The TEREM Immediate Medical Care Center Emergency Department in Jerusalem, Israel. TYPE OF PARTICIPANTS: Patients with traumatic lacerations requiring wound closure. MEASUREMENTS AND MAIN RESULTS: Lacerations considered appropriate for tissue adhesion tended to involve the scalp, chin, and forehead and were relatively shorter. The complication rate was low. This technique was painless, reduced the need for follow-up care, eliminated the need for local anesthesia and suture-removal visits, and was cost effective. Patients indicated a high level of satisfaction with tissue adhesion. CONCLUSION: Our report indicates that tissue bonding may be a preferred and cost-effective method of repair of appropriate traumatic lacerations in the ED. PMID- 8517571 TI - Immediate electronystagmography in the diagnosis of the dizzy patient. AB - STUDY OBJECTIVES: To determine whether the results of electronystagmography (ENG) testing improve an emergency physician's diagnosis of dizziness. DESIGN: Prospective, one-year. SETTING: University and three community hospital emergency departments. TYPE OF PARTICIPANTS: Ninety-three consecutive patients presenting with dizziness. INTERVENTIONS: ED impression was recorded after complete ED evaluation. An ENG was performed within one hour by an audiologist, who gave a reading of "central," "peripheral," or "normal." The result was given to the emergency physician, who was invited to revise his or her impression (the "ED impression after ENG result"). Final diagnosis was based on the ED impression and by contact with the patient's physician(s) as well as the patient by telephone after one and four weeks. Accuracy of ENG was assessed by comparing ENG reading with the final diagnosis using the chi(2) test. In addition, the contribution of ENG to ED diagnosis was assessed by comparing the accuracy of the ED impression after ENG reading with the ED impression alone using McNemar's test (hit versus no-hit). MEASUREMENTS AND MAIN RESULTS: Both ED impression and the ENG significantly correlated with the final diagnostic category (chi(2) = 104.9, P < .001; chi(2) = 70.79, P < .001, respectively). ENG correctly diagnosed nine of 11 patients with central dizziness. Of 23 patients with undetermined cause after ED evaluation, ENG correctly identified seven patients with peripheral dizziness and three with central dizziness. ED impression after ENG reading was more accurate than ED impression alone (chi(2) = 6.13, P < .05). CONCLUSION: Emergency physicians correctly categorized most dizzy patients, but audiologist performance and interpretation of an ENG significantly improved this categorization. ENG may have the potential to identify clinically unsuspected central dizziness and to categorize dizziness of "unknown" cause. Further study is needed to determine whether ENG could be performed by modifying certain types of heart monitors available in the ED. PMID- 8517573 TI - Minor head injury: a proposed strategy for emergency management. PMID- 8517574 TI - Variations in clinical guidelines. PMID- 8517575 TI - Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research. AB - STUDY OBJECTIVE: To develop guidelines for the care of infants and children from birth to 36 months of age with fever without source. PARTICIPANTS AND SETTING: An expert panel of senior academic faculty with expertise in pediatrics and infectious diseases or emergency medicine. DESIGN AND INTERVENTION: A comprehensive literature search was used to identify all publications pertinent to the management of the febrile child. When appropriate, meta-analysis was used to combine the results of multiple studies. One or more specific management strategies were proposed for each of the decision nodes in draft management algorithms. The draft algorithms, selected publications, and the meta-analyses were provided to the panel, which determined the final guidelines using the modified Delphi technique. RESULTS: All toxic-appearing infants and children and all febrile infants less than 28 days of age should be hospitalized for parenteral antibiotic therapy. Febrile infants 28 to 90 days of age defined at low risk by specific clinical and laboratory criteria may be managed as outpatients if close follow-up is assured. Older children with fever less than 39.0 C without source need no laboratory tests or antibiotics. Children 3 to 36 months of age with fever of 39.0 C or more and whose WBC count is 15,000/mm3 or more should have a blood culture and be treated with antibiotics pending culture results. Urine cultures should be obtained from all boys 6 months of age or less and all girls 2 years of age or less who are treated with antibiotics. CONCLUSION: These guidelines do not eliminate all risk or strictly confine antibiotic treatment to children likely to have occult bacteremia. Physicians may individualize therapy based on clinical circumstances or adopt a variation of these guidelines based on a different interpretation of the evidence. PMID- 8517576 TI - Evaluation and treatment of minors: reference on consent. PMID- 8517577 TI - Avulsion of the iliac crest apophysis: a rare fracture in adolescent athletes. AB - We report a case of an iliac apophyseal fracture in a 15-year-old boy, sustained while swinging a baseball bat. He presented with right hip pain one hour after the injury occurred. Diagnosis was made on the basis of radiographs of the pelvis. Pelvic avulsion fractures are uncommon injuries, seen almost exclusively in adolescent athletes. The iliac crest is an unusual site of injury for this avulsion fracture. Only one other well-described case of an acute, noncontact fracture of the iliac apophysis with a similar mechanism of injury has been reported. PMID- 8517578 TI - Diaphragmatic hernia masquerading as pneumothorax in two toddlers. AB - In two separate incidents, two toddlers with no previous history of respiratory ailments presented to the emergency department of a children's hospital with progressive respiratory distress. Both children had unilateral lung findings on auscultation and initial chest radiographs that were consistent with a pneumothorax. Thoracostomy and chest tube insertion were performed during initial resuscitation efforts. In both cases, subsequent radiographs revealed that the stomach was located in the left hemithorax, suggestive of a diaphragmatic hernia. Nasogastric tube insertion relieved the respiratory distress of these two children. Recognition of the "acquired" congenital diaphragmatic hernia in the setting of extreme aerophagia or mild abdominal trauma may prevent unnecessary procedures during the resuscitation of children with acute respiratory distress and unilateral lung findings. PMID- 8517579 TI - Use of amrinone and glucagon in a case of calcium channel blocker overdose. AB - Hypotension resulting from calcium channel blocker ingestion often is refractory to standard therapeutic modalities. Amrinone and glucagon have been used separately and in combination with other agents in the treatment of calcium channel blocker overdose. We report the successful use of both amrinone and glucagon in the treatment of a 30-year-old woman who ingested 3.6 g of verapamil and presented with refractory hypotension. The use of the two agents together may provide improved inotropic support with minimal increases in myocardial oxygen consumption. In this case, the combination of amrinone and glucagon was safe and effective in the management of the hemodynamic instability associated with calcium channel blocker overdose. PMID- 8517580 TI - The use of glucagon in a case of calcium channel blocker overdose. AB - The hypotension and myocardial depression that result from calcium channel blocker ingestion often are refractory to standard therapeutic modalities. Anecdotal reports on the use of glucagon have failed to show significant hemodynamic improvement. We report the first case of calcium channel blocker overdose that responded to glucagon. We conclude that glucagon is safe and effective in the management of hemodynamic instability associated with calcium channel blocker poisonings. PMID- 8517581 TI - Amelioration of nifedipine poisoning associated with glucagon therapy. AB - Glucagon relieves calcium channel blocker-induced hypotension in animal studies. There are no published case reports of glucagon relieving hypotension in patients with calcium channel blocker poisoning. We describe a patient who developed hypotension after ingestion of 900 mg nifedipine. Therapy with IV lactated Ringer's solution and calcium chloride alone did not relieve his hypotension. However, hypotension rapidly resolved after the addition of IV glucagon therapy. This is the first case report of glucagon therapy at least temporally associated with relief of hypotension in a patient with calcium channel blocker poisoning. More research is needed to determine the appropriate role for glucagon in treating patients with calcium channel blocker poisoning. PMID- 8517582 TI - Gastric alkalinization in the treatment of cocaine toxicity. PMID- 8517583 TI - Role of the SARS nurse. PMID- 8517584 TI - Log-linear modeling. PMID- 8517585 TI - Methylcellulose as a contact lens irrigant when silicone oil is used in vitreoretinal surgery. AB - When silicone oil, a hydrophobic agent, is injected into the vitreous cavity during the course of vitrectomy operations, often some escapes outside the eye, and a mixture of oil and water forms under the infusion contact lens, markedly interfering with visibility. We found that a viscous solution of methylcellulose 1.75% in saline used as the infusion contact lens irrigant, instead of a saline solution alone, can prevent silicone oil from entering under the contact lens, thus avoiding this difficulty. PMID- 8517586 TI - Retinal detachment as a complication of neodymium: yttrium aluminum garnet laser cyclophotocoagulation. AB - We report a traction retinal detachment that developed within one month of transscleral neodymium: yttrium aluminum garnet (Nd:YAG) laser cyclophotocoagulation, a previously unreported complication of the new cyclodestructive procedure. A 17-year-old boy was referred to our department with uncontrolled aphakic glaucoma OD after having undergone cyclocryotherapy twice. Three treatments with transscleral Nd:YAG cyclophotocoagulation were done over nine months to lower his intraocular pressure. Hypotony and traction retinal detachment occurred after the third laser treatment and was managed successfully by vitrectomy with a fluid-gas exchange. Thus, the possibility of this additional complication should be remembered when doing transscleral Nd:YAG cyclophotocoagulation. PMID- 8517587 TI - Flow cytometric study of anterior chamber aqueous humor after neodymium: yttrium aluminum garnet laser iridotomy. AB - Laser iridotomy is a safe and effective treatment of pupillary-block glaucoma; however, increased intraocular pressure (IOP) may occur after the procedure. A flow cytometric study of aqueous humor was done 1.5 hours after neodymium: yttrium aluminum garnet laser iridotomy in 20 eyes. This sensitive and precise method did not reveal an apparent correlation between the degree of postoperative IOP spike and the amount of inflammatory cells or cellular debris induced by laser iridotomy. Although slit-lamp examination showed many "cells" in the anterior chamber in most after laser iridotomy, DNA histography found only scanty chromatin coating cells. We believe the so-called cells observed using slit-lamp biomicroscopy might not all be real cellular aggregates but rather aggregates of protein or fibrin in some situations. PMID- 8517588 TI - Steroid treatment of radiation-induced choroidopathy. AB - Irradiation has been an important form of treatment of both ocular and cerebral neoplasms for decades. We report the case of a patient who underwent external beam irradiation to treat an astrocytoma of the left parietotemporal region. Sixteen months later, the patient developed radiation choroidopathy OS. Although not spontaneously resolvable, this case suggests that radiation choroidopathy can be treated successfully by the prompt and repeated application of both local and systemic corticosteroid preparations. PMID- 8517590 TI - Nonmydriatic retinal color photography in young Indian diabetic patients. AB - Retinopathy was assessed using a Canon nonmydriatic retinal camera (CR-45NM) in 42 young Indian diabetic patients (26 with malnutrition-related and 16 with insulin-dependent diabetes). Four patients with malnutrition-related diabetes (15.38%) had retinopathy (Level 3 in all 4). The duration of diabetes in them was 3.25 years. None of the four had hypertension or albuminuria. Five patients with insulin-dependent diabetes mellitus (31.25%) had retinopathy (Level 2 in 1 patient, Level 3 in 2, Level 5 and 6.5 in 1 each). The duration of diabetes in this group was 9.7 years. Three each (60%) had albuminuria and hypertension. Thus, retinopathy seemed to occur earlier in patients with malnutrition-related diabetes, and its incidence was discordant with that of nephropathy. PMID- 8517589 TI - Therapeutic use of topical cyclosporine. AB - Cyclosporine (cyclosporine A, CsA) is a selective immunosuppressant that inhibits T-cell activation. Its systemic use in the treatment of various ocular diseases has been successful. Topical CsA 2% was used in noncontrolled groups of seven patients with high-risk corneal transplants, two with peripheral corneal melting syndrome, three with chronic vernal keratoconjunctivitis, and two with ligneous conjunctivitis. Six (85%) of the seven high-risk corneal transplants remained clear after an average follow-up of 12 months (range, 10-15 months). Two (67%) of the three patients with chronic vernal conjunctivitis showed dramatic improvement in signs and symptoms after three months of therapy, but recurrence was the rule after the withdrawal of the drug. Peripheral corneal melting syndrome and ligneous conjunctivitis appeared to be refractory to topical CsA use. Systemic CsA levels were measured in all patients. PMID- 8517591 TI - Central retinal vein occlusion in two patients with immunoglobulin G multiple myeloma associated with blood hyperviscosity. AB - A 69-year-old man (Patient 1) complained of anorexia, lumbago, and seeing floaters OS. The results of laboratory tests showed immunoglobulin (Ig) G lambda type multiple myeloma associated with blood hyperviscosity. Retinal hemorrhages OD and central retinal vein occlusion OS were found. A 71-year-old woman (Patient 2) with IgG kappa-type multiple myeloma had blood hyperviscosity. Retinal microaneurysms OD and central retinal vein occlusion OS were found. We believe that our patients represent rare cases of IgG multiple myeloma associated with blood hyperviscosity and central retinal vein occlusion. PMID- 8517592 TI - Tapioca melanoma of the iris. AB - Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will discuss the anterior segment findings, secondary glaucoma, and fluorescein iris angiographic and histopathologic data from two patients, one with a single nodular type and one with a seeding type of tapioca melanoma of the iris. PMID- 8517593 TI - [Cardiovascular manifestations of hereditary dysplasias of connective tissue]. AB - The purpose of this study was to demonstrate the special features of cardiovascular effects in connective tissue disorders through a group of fifteen cases observed over a period of ten years. The group consisted of eleven cases of Marfan syndrome (or Marfan-like syndrome), two cases of pseudoxanthoma elasticum and two cases of Ehlers-Danlos disease. The cardiovascular lesions were as follows: 1) dissection of the ascending aorta which was confirmed and had been treated surgically in 2 cases; 2) aneurysmal dilatation of the ascending aorta in 5 cases; 3) moderate mitral valve prolapse, which was isolated in 2 other cases; 4) distention of the mitral valve in 2 cases; 5) mitral valve prolapse combined with tricuspid valve prolapse in 1 case; the mitral incompetence was severe and made it necessary to carry out mitral valve replacement; 6) moderate aortic valve prolapse combined with tricuspid prolapse in a case of type-I Ehlers-Danlos disease; 7) Fallot's tetralogy combined with Marfan's syndrome and treated surgically in one case; 8) severe hypertension with abnormalities of the iliac and renal arteries in one case of elastic pseudoxanthoma elasticum. In three cases complications occurred leading to death, extension of the dissection of the abdominal aorta and global recalcitrant heart failure respectively. The outcome in the other 12 cases, with a mean follow-up time of 3 and one half years (range: 3 years to 7 years) was not marked by complications. PMID- 8517594 TI - [Radiofrequency catheter ablation of accessory atrioventricular pathways: initial experience in 33 patients]. AB - The authors report their experience in endocavitary radio-frequency ablation of 37 secondary pathways carried out in 33 consecutive patients. The indications for radical treatment were based solely on clinical arguments in 15 patients, on a combination of disabling signs and threatening electrophysiological signs in 17 patients and on high retrograde permeability in 1 asymptomatic patient. Endocavitary exploration revealed 26 left lateral sites, 7 posterior paraseptal sites and 4 right lateral sites. The procedure was successful in 88% of cases. Electrophysiological follow-up, carried out routinely in all the patients 2 months after the procedure, revealed a single recurrence (3%) which was treated by radio-frequency again, this time with a successful outcome. There was only one complication, a complete AVBBB following ablation of a left posterior paraseptal Kent's bundle, which required a permanent pacemaker. These results were similar to those reported in the literature and clearly demonstrate the efficacy of radio frequency treatment of the secondary pathways, with a moderate risk of complication. These results were similar to those reported in the literature and clearly demonstrate the efficacy of radio-frequency treatment of the secondary pathways, with a moderate risk of complication. Recent advances in the field of endocavitary ablation have made it possible to change the method of handling symptomatic Wolff-Parkinson White syndromes, by enlarging the indications for radical treatment in order to enhance the comfort and quality of life of the patient. PMID- 8517595 TI - [Coronary disease in black Africans]. AB - Coronary artery disease remains rare (6% of all cardiovascular disease) in black Africa despite its progression in recent years. Infarcts in black Africans have similar characteristics to those seen in Western countries in patients aged under 40, notably regarding the frequency of infarcts as the first manifestation of the disease, the small number of stenoses and the incidence (18%) of patients with normal coronary arteriography (spasm? thrombosis?). Risk factors are the same as in Western countries, but the hemoglobin S or C trait could be a predisposing factor. The long-term outcome of infarcts is severe because of notable myocardial sequelae of imprecise origin: delayed hospitalisation and absence of thrombolysis? absence of angioplasty? socio-economic problems and lack of health education. PMID- 8517596 TI - [Digital arterial embolism after thrombosis of arteriovenous fistula]. AB - Four patients suffering from severe digital ischemia due to emboli originating from a thrombosed arteriovenous fistula were operated on. In all cases, a large aneurysm had developed on the efferent vein. Segmental resection of the fistula and of the aneurysm with or without reanastomosis of the artery was successfully performed in all patients; a thoracic sympathectomy was performed in one because of the severity of the ischemic symptoms. Progressive degenerative changes of the arterialized vein account for the development of an aneurysm at its level with secondary thrombosis. When performing an arteriovenous fistula, end-to-end or end to-side anastomosis of the artery prevents the occurrence of distal embolism in case of local thrombosis. Suppression of all aneurysmal fistulas is recommended whenever a kidney transplant ensures satisfactory function with sufficient follow up. PMID- 8517597 TI - [Listeria monocytogenes femoral aneurysm]. AB - Secondary infection of arterial aneurysms being a constantly possible complication, the bacteriological examination of peroperative specimens appears to be appropriate. Among responsible organisms, the presence of Listeria monocytogenes is very rare since only 13 cases have been reported in the literature. It is for this reason that it was felt to be of interest to report a new, entirely similar case of femoral aneurysm. PMID- 8517598 TI - [Chronic constrictive pericarditis after heart surgery. Apropos of a case]. AB - A case of pericarditis in a 52-year old patient following aorto-coronary shunt surgery is reported which gradually developed into chronic constrictive pericarditis. In this context, the diagnostic criteria of chronic constrictive pericarditis are recalled. The clinical criteria show little specificity; Doppler ultrasound provides good diagnostic information; CT scans and nuclear magnetic imaging can confirm the diagnostic. The post-heart surgery etiology has increased in recent years. The only real treatment is surgical and consists of pericardial decortication. PMID- 8517599 TI - [Syphilitic aortic insufficiency. Apropos of a case]. AB - The authors report a case of aortic insufficiency with aneurysm of the ascending aorta of syphilitic origin. The diagnosis was made only histologically in the presence of a syphilitic granuloma. This opportunity is taken to review the various aspects of cardiovascular syphilis. PMID- 8517600 TI - [Superior vena cava syndrome disclosing dissection of the aorta]. AB - The authors report a case of dissection of the aorta presenting as a superior vena cava syndrome. Because of the rarity of such a manifestation, this dissection was not suspected before CT scan. A review of the literature confirms the rarity of obstruction of the superior vena cava during dissection and indicates that it results from a compressive hemomediastinum. In this case, the superior vena cava was compressed by the ascending aorta itself, which had become very large but had not ruptured into the mediastinum. This forms the basis of the originality of the case. PMID- 8517601 TI - [From venous ligation to vena cava filter. Objectives and hazards of vena cava interruption]. AB - Starting from the use of venous ligatures (the first measure employed), methods for the prevention of pulmonary embolism have been perfected to arrive now at the endocaval insertion of permanent or temporary filters. Both in the materials used and the techniques employed, major progress has been made and incidents and accidents (thrombosis, migration, perforation of the venous wall) have become rarer. The efficacy of classical treatment methods (anticoagulants, early mobilisation, hemodilution, etc.), the preventive value of which has long been recognized, must also be taken into account when making the decision. Specific indications for vena cava interruption procedures can be defined, but their very efficacy and the ease of insertion of filters have led to indications (on a prophylactic or adjuvant basis) which are often--and other than in special situations--dubious insofar as the prevention of embolism does not always require interruption of the vena cava and that complete freeing of the iliac veins is generally not a priority objective. PMID- 8517602 TI - [Intravenous and oral propafenone in the treatment and prevention of paroxysmal atrial fibrillation]. AB - The efficacy of propafenone in the treatment of paroxysmal atrial fibrillation was investigated in 16 patients presenting with frequent and/or poorly tolerated paroxysmal atrial fibrillation despite prophylactic treatment in 13 patients. Prolonged atrial fibrillation (> 10 minutes) was triggered in 16 patients following a standard atrial stimulation protocol. Intravenous injection of propafenone (2 mg/kg over 5 minutes) restored sinus rhythm in 12 patients (75%) within 15 minutes after the end of the injection. In five of the 10 patients in whom this was possible, propafenone prevented the induction of atrial fibrillation in response to programmed stimulation by the same protocol. Oral propafenone (900 mg/24 hours) was indicated in 11 patients. The treatment was discontinued in 1 patient due to severe dizziness. Atrial fibrillation recurred in 4 patients 10 to 91 days after treatment began. With a mean follow-up time of 8 months, 4 patients had been brought under control and 2 had relapsed despite a generally beneficial effect. Three patients suffered side effects which did not make it necessary to stop treatment. This study suggests that intravenous propafenone is effective against persistent atrial fibrillation induced by stimulation. Oral propafenone may be useful for the prevention of attacks of recalcitrant paroxysmal atrial fibrillation. PMID- 8517603 TI - Plasma bicarbonate assays--time for a new look? PMID- 8517604 TI - The investigation of hypoglycaemia during childhood. PMID- 8517605 TI - Audit of automated requesting of serum magnesium measurement in patients with hypocalcaemia. AB - Laboratory computer records for 71 consecutive hypocalcaemic patients (albumin adjusted calcium < 2.00 mmol/L) without chronic renal failure revealed that 50 (70%) did not have serum magnesium measured. A second review of computer records was carried out 6 months after the initiation of an automated requesting program. This identified 14 patients with hypomagnesaemia (serum magnesium < 0.70 mmol/L) who may otherwise have been undiagnosed. The direct cost to the laboratory was an additional 19 magnesium analyses per month. It is concluded that hypomagnesaemia is commonly associated with hypocalcaemia but is under-diagnosed. Automated requesting of serum magnesium measurement is a cost-effective way of identifying these patients. However, the fact that only half of these patients had follow-up magnesium requests suggests that there may be a need for further education of clinicians in the significance of hypomagnesaemia. PMID- 8517606 TI - A survey of diagnoses in patients with a low intact parathyroid hormone concentration. AB - Intact parathyroid hormone (PTH) was analysed in 1107 samples over a 13 month period. Of these, 181 samples (16%) gave results of < or = 1 pmol/L and the case notes of 169 of these 181 patients were examined. Eighty-two patients (48%) were hypercalcaemic at the time of the PTH assay. As expected, the most common diagnosis in this group was hypercalcaemia of malignancy but surprisingly this accounted for only 42 of the hypercalcaemic patients; an unexpectedly high proportion (20 patients) had chronic renal failure with hypercalcaemia due to excessive treatment with 1 alpha-hydroxycholecalciferol; eight patients had transient unexplained hypercalcemia and the remaining 12 patients were hypercalcaemic for a variety of causes including immobilization, bendrofluazide treatment and Paget's disease. Fifty-nine patients (35%) were normocalcaemic: 26 had osteoporosis, 10 had chronic renal failure and the remainder had a wide range of diagnoses. It is possible that the low intact PTH result in a proportion of the normocalcaemic group was caused by ingestion of calcium tablets prior to blood sampling for PTH. Twenty-eight patients (17%) were hypocalcaemic: 24 of these had hypoparathyroidism, two had chronic renal failure and two had transient unexplained hypocalcaemia. PMID- 8517607 TI - The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism. AB - The relationship between serum cholesterol, thyrotropin, thyroxine and triiodothyronine was investigated in 456 male patients with suspected hypothyroidism. The correlation between serum cholesterol and serum thyroxine (r = 0.0572) and between serum cholesterol and serum triiodothyronine (r = 0.1136) were not significant but the correlation between serum cholesterol and TSH (r = 0.0376) was significant (P < 0.001). The mean serum cholesterol was only significantly increased in the patient groups with a serum TSH greater than 20 mU/L. In 26 patients treated for hypothyroidism with thyroxine replacement there was a significant correlation between the decrease in serum cholesterol and the decrease in serum TSH (r = 0.5334, P < 0.01) but there was poor correlation between the decrease in cholesterol and either the increase in serum triiodothyronine or the increase in serum thyroxine. PMID- 8517608 TI - Biological variation in glycated proteins. AB - The high degree of individuality in the fructosamine assay has been ascribed to non-specific interferences in the assay. To investigate this, we measured the biological variability of 10 non-diabetic subjects using the fructosamine assay, the new fructosamine plus assay, glycated albumin and glycated total plasma proteins by affinity chromatography. The total variation of the two fructosamine assays was half that of the affinity chromatography assays. This was mainly due to the greater analytical imprecision of the affinity chromatography assays. The resulting high index of heterogeneity for both affinity methods makes it difficult to assess the significance of changes in serial results. The within subject variation made a small contribution to the total variation for all the assays, and was particularly low for the fructosamine assays. This suggests that any non-specific component makes a constant contribution to the measured fructosamine activity in non-diabetic subjects. The fructosamine assays therefore have significant advantages over the affinity chromatography methods as indices of medium-term glycaemic control. PMID- 8517609 TI - Purified haemoglobin preparations in the evaluation of HbA1c determination by ion exchange chromatography. AB - The use of ion exchange resins for the estimation of HbA1c in clinical samples rests on the assumption that HbA1c is effectively and efficiently separated from other N-terminally modified haemoglobins and from HbA0. To test this assumption, we applied highly purified preparations of HbA(1a+1b, HbA1c and HbA0 to ion exchange minicolumns, using conditions of application simulating actual blood samples and the first and second elution buffers provided by the manufacturer. The authenticity and purity of the applied haemoglobin preparations were documented by high performance liquid chromatography, gel electrophoresis and carbohydrate content. About 40% of the applied HbA(1a+1b) eluted in the first fraction; 45% eluted in the second fraction, and 10% to 15% required 1 mol/L NaCl to elute from the column. Of the applied HbA1c, 65-80% eluted where expected in the second fraction, about 20% required 1 mol/L NaCl to elute from the column, and the remainder eluted with HbA(1a+1b). Some 3-6% of pure HbA0 applied to minicolumns emerged in the second fraction, with the remainder eluting as expected after making the buffer 1 mol/L in NaCl. The results indicate that the fraction eluting from ion exchange minicolumn chromatography that is designated 'HbA1c' contains HbA(1a+1b), and that a substantial portion of the HbA1c in an applied sample does not elute in this fraction. PMID- 8517610 TI - Clinical relevance of serum amyloid A protein monitoring in urinary tract infections. AB - We have evaluated the clinical relevance of monitoring acute phase proteins in severe urinary tract infection. Body temperature, white blood cell count, erythrocyte sedimentation rate, serum amyloid A protein (SAA), C-reactive protein (CRP), alpha-1-antichymotrypsin (ACT) and alpha-1-acid glycoprotein (AGP) were determined daily in sera from 18 treated patients. Two patterns of response could be identified: responders and non-responders whose therapy had to be changed. Mean values for each acute phase protein were calculated daily in both responders and non-responders. Statistical evaluation of the significance between the means for each protein was also performed on a daily basis and showed P < 0.01 for SAA and CRP on day 3, for ACT on day 5, and for AGP on day 6. SAA and CRP appear to be the most reliable markers for antimicrobial therapy monitoring in patients with urinary tract infections. PMID- 8517611 TI - A rapid enzyme-linked immunosorbent assay for serum amyloid A using sequence specific antibodies. AB - A microtitre plate based enzyme-linked immunosorbent assay for determining the concentration of serum amyloid A (SAA) is described. The method employs easily produced sequence-specific rabbit antibodies and the preferential absorption of SAA to polystyrene, which obviates the use of capture antibodies and allows an assay time of only 3.5 h, so that the diagnostic potential of the SAA level as a rapid and reliable marker for inflammation can be fully exploited. The assay has a working concentration range of 0.1-2500 mg/L, which embraces the known biological variation of the SAA concentration. The intra-assay coefficient of variation (CV) for SAA concentrations above 10 mg/L is between 1.6 and 3.3% and the interassay CV between 3.0 and 4.2%. Recovery of SAA added to serum is from 96 to 102%. PMID- 8517612 TI - A simple spectrophotometric assay for long-chain acyl-CoA dehydrogenase activity measurements in human skin fibroblasts. AB - Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is an autosomal recessive disorder of fatty acid metabolism characterized by hypoglycemia, muscle weakness and hepato- and cardiomegaly to varying extents. Analysis of organic acids in urine usually reveals dicarboxylic aciduria with elevated levels of adipic, suberic and sebacic acids as well as longer chain dicarboxylic acids. Correct diagnosis of suspected patients requires measurement of LCAD in tissue or preferably, white blood cells and/or cultured skin fibroblasts. In this paper we present a simple spectrophotometric enzyme assay based on the use of ferricenium hexafluorophosphate as electron acceptor. Under optimized conditions the method presented allowed unequivocal identification of LCAD-deficiency in fibroblast homogenates. PMID- 8517613 TI - An adaptable computer interface for radioimmunoassay. AB - To assist data handling of results derived from radioimmunoassay the RIACalc Multigamma counter package was interfaced to a laboratory information system. The interface was bidirectional and allowed transfer of worklists and results. A suite of programs was written for the laboratory information system that enabled flexible data processing to meet a range of laboratory requirements. One utility within the suite contained a simple user definable rule based routine for automatically requesting additional tests. Use of the interface and new software improved laboratory efficiency and illustrated the potential benefits of decision making systems. PMID- 8517614 TI - Between-country comparability of clinical chemistry results: an international quality assessment survey of 17 analytes in six European countries through existing national schemes. AB - Two lyophilized control sera were distributed through seven national external quality assessment schemes in six European countries--Belgium, Switzerland, France, The Netherlands, Sweden and the United Kingdom--participated in the study. The results for 17 routine analytes were obtained from almost 5000 laboratories for the two sera. The organizers of the schemes were asked to process the results according to a common outlier removal procedure, and submit method-related data if available. The two sera were also distributed through the external/internal scheme of The Netherlands, and the within-laboratory standard deviations calculated in this scheme have been used in a scaling procedure for the external mean values and between-laboratory standard deviations of the participating countries. The results show remarkable agreement in the national mean values for practically all analytes, but considerable differences in the between-laboratory variation. Data from comparable method groups was obtained for 12 analytes from Belgium, France, The Netherlands and the UK. Though revealing some specific differences between methods and countries, the method-related data are generally in agreement with the all-method data. In this study reference method values were only available for cholesterol. The high degree of agreement found suggests, however, that mutual recognition of all-method mean values in national schemes could be acceptable, especially for analytes for which reliable reference methods are not available. The major element of variation is between laboratory rather than between-country. PMID- 8517615 TI - Hypomagnesaemia and fits complicating paediatric cardiac surgery. PMID- 8517616 TI - Identification of 3-hydroxyisovalerylcarnitine in the urine of a patient with multiple carboxylase deficiency. PMID- 8517617 TI - Urine protein electrophoresis without sample concentration: an evaluation of two methods. PMID- 8517618 TI - Salivary immunoglobulin A in irritable bowel syndrome: no correlation with anxiety. PMID- 8517619 TI - A high serum concentration of azlocillin affects routine biochemical analyses. PMID- 8517620 TI - Hyperlipidaemia and diabetes. PMID- 8517621 TI - Molecular biology techniques. PMID- 8517622 TI - [Caroli's disease and Jaccoud's arthropathy]. AB - The authors present a case of left unilobar Caroli's disease in a 83-year-old woman associated with a Jaccoud's arthropathy of the hands. The role of repeated episodes of cholangitis and genetic tendency is discussed... PMID- 8517623 TI - [Hydatid cyst of the psoas muscle]. AB - Hydatid cysts in the psoas muscle are unusual. The authors report a case of a hydatid cyst which had developed within the psoas muscle and was detected from a mass in the left iliac fossa which was diagnosed before surgery by ultrasound and a CT scan, which remain the preferred primary examinations for the investigation of masses of this type. The authors discuss the various possible clinical and paraclinical contexts and recommend total pericystectomy of a closed cyst as the best treatment following extraperitoneal iliac surgical opening. PMID- 8517624 TI - [Epithelial dysplasia of the digestive tract and flow cytometry]. AB - The early diagnosis of digestive cancer is usually based on the detection of the presence epithelial histological abnormalities known as dysplasia. The histological features described constitute an intermediate step between normal tissue and actual cancer. Two degrees of dysplasia are now distinguished: moderate dysplasia and severe dysplasia (the latter being equivalent to in situ cancer or stage 0 cancer). The difficulty in reliably identifying and classifying dysplasia has led to the development of additional methods able to detect abnormalities of the genetic material, particularly of DNA. The use of flow cytometry to examine tissue makes it possible to analyse the DNA content of the tissue nucleus by nucleus. Normal tissues have a normal DNA content and are described as "diploid". Tumor tissues frequently contain abnormal quantities of DNA and are described as "aneuploid". Pre-cancerous aneuploidism could be identified before cancer develops and detected in dysplastic states. The authors report their own experience and that of many other authors of the value of this additional method of investigating precancerous lesions of the digestive tract. PMID- 8517625 TI - [Cancer of the rectum: epidemiologic aspects]. PMID- 8517626 TI - [Echoendoscopy and cancer of the rectum]. PMID- 8517627 TI - [Pre-operative radiotherapy and sphincter conservation in cancer of the rectum]. PMID- 8517628 TI - [Conservative treatment of cancer of the lower rectum. Radiobiologic basis of treatment]. PMID- 8517629 TI - [Cancer of the lower rectum. The role of surgery in combined therapy. An argument for the most conservative treatment of the anal sphincter]. PMID- 8517630 TI - [Medical treatment of colorectal cancers: evaluation]. PMID- 8517631 TI - [The contribution of the Department of Health in overseas diet and nutrition]. AB - This article reminds the contribution of Health and Medical Services in overseas territories and other developing countries. Seconded to Health Services, Pasteur Institutes, other scientific research Organisations, and International Organisations (FAO, WHO), medical doctors and pharmacists, properly trained in nutrition, have studied under-nutrition and malnutrition, and their effects on the health of the populations and the economy of their countries. Later, in cooperation with all departments concerned, they have realised a number of applied programmes, aiming at a real improvement in the situation or even the eradication of nutritional deficiencies. However the article deals mainly with actions related to food production and distribution, from the establishment of a national food policy to agriculture planning and evaluation, including specific, applied nutrition programmes in agriculture development and supplementary feeding programmes. PMID- 8517632 TI - [Endoscopic ligation: a new technic in the treatment of esophageal varices]. PMID- 8517633 TI - [The conferences at Bichat 1992. Therapeutic exchanges in gastroenterology]. PMID- 8517634 TI - Effect of nutrients on plasma corticosteroid concentration in cold-stressed rats. AB - Little is known about the mechanisms as to how nutrients affect plasma corticosteroids in cold-stressed and starved animals. Therefore, cold-stressed rats (maintained at 7 degrees C) were fasted (control) or fed a balanced diet (casein 20 wt%, fat 5 wt%, starch 70 wt% and vitamin-mineral premix 5 wt%) or the following dietary nutrients for 72 h: casein, lard, starch, glycerol, stearic acid, leucine or glutamic acid. The animals were then killed and plasma corticosteroid concentrations (PCC) were determined. PCC were significantly reduced (p < 0.05) in cold-stressed animals fed a balanced diet (16.95 micrograms/100 ml plasma) compared to the fasted cold-stressed controls (FCSC) (24.16 micrograms/100 ml plasma). Additionally, corticosteroid concentrations (micrograms/100 ml plasma) of animals fed the following specific nutrients were also significantly lower than the FCSC values: starch (15.53), lard (12.01), stearic acid (12.74), glycerol (13.32) and leucine (16.03). Casein and glutamic acid did not significantly alter plasma corticosteroid levels relative to the FCSC concentration. It is concluded that certain specific building blocks of nutrient classes, i.e. stearic acid or glycerol, can alter PCC to the same extent as the parent compound (lard), however the individual components of casein, a complex nutrient, i.e. leucine, a ketogenic amino acid, versus glutamic acid, a glycogenic amino acid, may elicit a different PCC effect. PMID- 8517635 TI - Weak resistance to oxidation of native lipoproteins in Wistar rats. AB - We report an impressive decline in plasma lipid resistance to oxidation during Triton-WR-1339-induced hyperlipidemia in rats. This decline is associated with a modification in the balances between alpha-tocopherol and lipids and alpha tocopherol and ascorbate. These results are consistent with a weak resistance of accumulated native lipoproteins in plasma to oxidation, during a 6-hour time course, and they suggest a misunderstood role of lipoprotein catabolic enzymes: to improve this characteristic. Conclusively, the results lead us to propound Triton-induced hyperlipidemia as an original model for studying the balance impairment between antioxidants and oxidizable substrates. PMID- 8517636 TI - Increased susceptibility to undergo lipid peroxidation of chylomicrons and low density lipoprotein in celiac disease. AB - Gastrointestinal injury involves oxidative damage as the result of oxygen-derived free radicals which are formed during the inflammatory reactions. Chylomicrons which are synthesized by the intestine can thus be exposed to lipid peroxidation in celiac disease. Similarly, low-density lipoprotein (LDL) propensity to oxidation may be enhanced as a result of a direct or indirect effect of the oxidative process. To resolve these possibilities, plasma chylomicrons and LDL were isolated from a patient with celiac disease and from a control healthy subject before and 3 h after a fat-rich meal, and their propensity to copper induced lipid peroxidation was then analyzed. The patient's chylomicrons, its LDL that was obtained before the fat-rich meal and its LDL that was obtained after the meal demonstrated 220, 39 and 48% elevation in their content of thiobarbituric-acid-reactive substances in comparison with the control lipoproteins. After a complete recovery of the patient's intestine, the susceptibility of the patient lipoproteins to in vitro oxidation returned toward normal levels. In the patient LDL fraction (obtained either before or after the fat-rich meal), but not in the patient's chylomicrons, the carotenoid content was reduced by 70%, vitamin E by 45%, and the LDL content of arachidonic acid was increased by 70% in comparison with the control lipoproteins. On recovery of the patient and return of the intestine to its normal morphology, normalization of all of these constituents was achieved. PMID- 8517637 TI - Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. AB - Low-density lipoprotein (LDL) oxidation and macrophage cholesterol accumulation are both involved in atherogenesis. Recently it was shown that feeding rabbits or humans with an oleic-acid-rich diet reduced the susceptibility of their LDL to in vitro oxidation. Since olive oil is highly enriched with oleic acid, we tested the effect of olive oil supplementation (50 g/day) to the diet of 10 healthy male subjects, during a 2-week period, on macrophage uptake of their LDL and on the propensity of their LDL to oxidation (with copper ions). Olive oil supplementation to the diet resulted in LDL enrichment with oleic acid (C18:1) and sitosterol. No effect on plasma cholesterol levels was found, but the LDL cholesteryl ester content was reduced (16%) whereas its unesterified cholesterol was increased (41%). Even after 1 week of the olive oil diet, the LDL susceptibility to in vitro oxidation was significantly reduced (p < 0.01). Macrophage uptake of LDL was studied by analysis of cellular cholesterol content and by analysis of the macrophage cholesterol esterification rates. LDL obtained after 1 and 2 weeks of the olive oil diet demonstrated reduced cellular uptake in comparison with LDL obtained before the supplementation of olive oil, by 50 and 61%, respectively. The LDL resistance to oxidation was shown by a reduction in its peroxide, malondialdehyde and conjugated diene content by 73, 28 and 32%, respectively. LDL incubation with oleic acid for the period of its oxidation with copper ions demonstrated a dose-dependent inhibition of lipoprotein oxidation by up to 72% as opposed to linoleic and arachidonic acids (50 microM) which increased LDL oxidation by 22 and 72%, respectively. Sitosterol, in a similar incubation system, inhibited LDL oxidation by up to 26%. We conclude that olive oil supplementation to the diet modifies LDL lipid composition and enriches the lipoprotein with oleic acid and sitosterol. The antiatherogenic properties of this modified lipoprotein may be related to its resistance to in vitro peroxidation and its reduced uptake by macrophages. PMID- 8517638 TI - Effects of right hemicolectomy on fecal nitrogen excretion in rats. AB - The influence of right hemicolectomy (RH) on fecal nitrogen excretion was determined with selected protein levels up to 25%. The endogenous fecal N was determined by extrapolating protein intake to zero. Fecal N was higher in RH than in control rats at all protein levels used. However, the slope of regression curves describing fecal nitrogen excretion was greater for RH compared with the control group. The endogenous fecal nitrogen was not significantly different between the two groups of rats. The feces from rats fed with 25% of protein were partitioned into individual fractions by physical separation and a study was made of the distribution of nitrogen in the bacterial, soluble and fiber fractions of the stool. RH decreased the N excreted in the bacterial fraction by 33% (from 1.71 +/- 0.32 to 1.15 +/- 0.18 mmol/day) and increased the N excreted in the soluble fraction by 280% (from 1.60 +/- 0.30 to 6.08 +/- 1.16 mmol/day). These results show that the RH increased the fecal N excretion and that this N is mainly in the soluble fraction. PMID- 8517639 TI - Effect of diet composition on protein requirements of children and adults in northern Mexico. AB - The overall vegetable and animal protein combinations of the diet in Northern Mexico were determined through a dietary population survey. Vegetable sources made up 45% and animal protein was 55% (45V/55A). Further combinations of up to 100% vegetable protein dietary mixtures (100V) were studied to test the sensibility of the variations on protein requirements of pre-school, school children and adults. Diets were analyzed for amino acid composition and in vivo protein digestibility in rats to estimate true protein requirements according to FAO/WHO/UNU (1985). The effect on the pre-school group showed the widest variation with 1.46 g/kg/day in the 45V/55A to 2.63 in the 100V. For the school aged children and adults the variations were 1.15-1.79 and 0.94-0.84 g/kg/day respectively. PMID- 8517640 TI - Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. AB - We report here the first orthotopic transplant model for human ovarian cancer. Histologically-intact patient specimens of ovarian cancer were transplanted by microsurgical techniques under the capsule of the nude mouse ovary. The human tumors grew locally and gave rise to a patient-like metastatic pattern including the parietal peritoneum, colon, omentum, and ascites. The orthotopic model described here should be useful for evaluating new therapeutics and diagnostics for ovarian cancer. PMID- 8517641 TI - Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice. AB - A metastatic model of human colon cancer has been previously established using orthotopic onplantation of histologically intact in tissue nude mice. In this study, effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) on Col-2-JCK, a human colon cancer xenograft, were evaluated using this model. When 5-FU and MMC were administered without OK-432, liver metastases were not reduced even at maximum tolerated doses of both drugs, although cecal tumor growth was significantly reduced. On the other hand, when combined with OK-432, both 5-FU and MMC reduced liver metastases with synergistic reduction of cecal tumor growth, demonstrating the potential of combining immunotherapy with chemotherapy against metastases. PMID- 8517642 TI - Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis: further evidence for patient-like hematogenous metastatic route. AB - We have developed an orthotopic transplant model of human cancer to immunodeficient mice utilizing microsurgical techniques with intact tissue. The resulting transplanted human tumors grow locally and metastasize in a clinical like pattern. However, there has been no definitive evidence in colon cancer that the human tumors metastasize via hematogenous route in nude mice. In the present study, in order to obtain definitive evidence of physiological spread of the human tumors, the primary tumors were resected 10 days after the initial orthotopic transplantation to the nude mice. The resection prevented metastases from forming, demonstrating that metastases of the human colon cancers occur after 10 days and by physiological and non-seeding mechanisms in the transplanted nude mice. PMID- 8517644 TI - The status of the surface enzyme guanidinobenzoatase on mature epithelial cells in sputum cell monolayers. AB - Mature epithelial cells derived from the sputum of normal healthy adults lack GB, while the epithelial cells of sputum collected from patients with lung tumours contain a spectrum of epithelial cells with active GB, some of which are clearly tumour cells, based upon their morphology. The presence of abnormal epithelial cells was confirmed by the cytologist whilst observing the fluorescent stained cells and later by independent cytological analysis of these same cells employing conventional stains. PMID- 8517643 TI - Immunohistochemical and in situ hybridization analysis of p53 in human endometrial carcinoma of the uterus. AB - We examined the immunohistochemical localization of p53, a tumor suppressor gene, in thirty-three specimens of uterine endometrial carcinoma which included one case of carcinosarcoma, eleven specimens of endometrial hyperplasia and ten specimens of normal endometrium. We also analyzed the association between the immunolocalization of p53 protein and the clinical and pathological parameters of endometrial concern. We also determined whether p53 mRNA is overexpressed in these specimens by in situ hybridization and simultaneous immunohistochemistry and in situ hybridization. Immunohistochemistry was performed using the monoclonal antibodies pAbDO-7 and pAb1801, and polyclonal antibody pAbCM-1. Immunoreactive p53 was observed in the nuclei of the cancer cells in 15/33 (45%) by pAbDO-7, 11/26 (42%) by pAb1801, and 16/33 (48%) by pAbCM-1. No p53 immunoactivity could be detected in either hyperplasia or normal endometrium except for a case in which the endometrium was in the secretory phase. There was no significant relationship between p53 immunostaining as determined by pAbDO-7, and age, clinical stage, histological grade or depth of myometrial invasion. We employed the 35S-labeled antisense single stranded synthetic oligonucleotide probe, ON102, to perform in situ hybridization and simultaneous immunohistochemistry and in situ hybridization. In every case of endometrial carcinoma studied, no significant accumulation of the p53 hybridization signal was observed in carcinoma cells. This indicated that overexpression of p53, as observed by immunohistochemical staining, is not due to an increase in the steady state level of p53 mRNA in carcinoma cells. These results suggest that immunostaining of p53 is associated with the malignant phenotype, but does not correlate with the biological behavior of human endometrial carcinoma. PMID- 8517645 TI - Cytotoxicity of adriamycin-containing immunoliposomes targeted with anti ganglioside monoclonal antibodies. AB - GM2 and GD2 have been intensely studied as tumor antigens of neuroectodermal origin tumors. We have established several mouse or rat IgM anti-ganglioside GM2 and GD2 MoAbs and applied them in antigen-specific drug delivery. In the immunofluorescence assay, anti-GM2 MoAbs bound to neuroblastoma cells and leukemia cells, and anti-GD2 MoAb bound to neuroblastoma cells and melanoma cells. Sulfhydryl subunits of reduced IgM were directly coupled to maleimide groups on the surface of the liposomes followed by the incorporation of adriamycin by the use of Na+/K+ chemical gradient. The resultant immunoliposomes had a size of 86 nm-diameter containing approximately 400 molecules of adriamycin in its unilamellar structure and 17 molecules of the MoAb on its surface. Mouse anti-GM2 MoAb lost the binding specificity when covalently bound to the liposomes. The immunoliposome coupled with mouse anti-GD2 MoAb retained targeting activity to the antigen-positive neuroblastoma cells, IMR-32. However, it did not kill IMR-32 cells, probably because the amount of adriamycin taken up by the tumor cell was below the fatal amount. The immunoliposome coupled with rat anti GM2 MoAbs delivered adriamycin to the neuroblastoma cells, IMR-32, and leukemia cells, TYH, in the antigen-specific manner. It also target-specifically suppressed the (3H)thymidine-uptake of the cells while the same concentration of adriamycin in the free form killed all the cell lines examined. IMR-32 cells had GM2 and GD2 in almost the same amounts, and interacted with either mouse anti-GD2 MoAb--immunoliposome or rat anti-GM2 MoAb-immunoliposome. The different cytotoxic activities of the two immunoliposomes against IMR-32 cells was probably due to the difference in the facility of internalization of the immunoliposomes after binding. PMID- 8517646 TI - Clinical pharmacology of 11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11 diazatetracyclo (7.4.1.0(2,7).0(10,12) tetradeca-2,4,6-trien-6,9-diyl diacetate (FK 973). AB - FK 973, a novel substituted dihydrobenzoxazine structurally similar to mitomycin C, is a derivative of the product isolated from Streptomyces sandaensis. In vitro and in rodents, it is a potent antitumor agent. During Phase I clinical trials, we evaluated the pharmacologic properties of FK 973 in eight adenocarcinoma patients after a 30-min i.v. infusion of doses ranging from 7 to 45mg/m2. An established enzyme immunoassay that measures the stable deacetylated active metabolite FR66980 showed that the plasma drug levels declined biphasically with a terminal half life (t1/2 beta) of 4.7 +/- 1.6hr (mean +/- S.D.) The total clearance rate was 438 +/- 113ml/(min/m2). Both the maximum plasma drug concentrations (Cmax) and the area under the concentration-versus-time curve (AUC) were dose related. In addition to nausea and vomiting, alopecia, and myelosuppression, three patients experienced a delayed vascular-leak syndrome. The 3 patients had received doses among the highest studied, and the toxicity appeared to be dose related and cumulative. The evidence suggests that higher doses generated higher Cmax and AUC values, which may be correlated with toxic effects. PMID- 8517647 TI - Antitumor activity of idarubicin, a derivative of daunorubicin, against drug sensitive and resistant P388 leukemia. AB - Idarubicin (IDA) possessed high antitumor activity against mouse P388 leukemia. When P388 leukemia bearing mice were administered an optimal dose of IDA intravenously, 200-250% of T/C and some cured mice were obtained. IDA showed a partial but significant effect against daunorubicin (DNR)-resistant P388 leukemia, whereas DNR, its parent drug, did not. Although IDA failed to show activity against doxorubicin (DX)- and aclarubicin (ACR)-resistant P388 leukemia in this study, IDA might have chemotherapeutic effects in patients in relapse and refractory to other anthracyclines. This assumption is supported by the results on the growth inhibition study in vitro. Among the metabolites, only idarubicinol showed cytotoxicity against P388 leukemia and idarubicinol showed 38% of the activity of IDA, indicating that the active components in animals could be IDA and idarubicinol. The combination of IDA and Ara-C induced some additive effect in P388 leukemia bearing mice as compared to the results with single drug usage. PMID- 8517648 TI - Glutathione S-transferase in human esophageal carcinoma. AB - The expression of human glutathione S-transferase-pi (GST-pi) in esophageal squamous cell carcinoma and in corresponding morphologically normal mucosa from 17 patients was examined by Northern blots, in situ hybridization and immunohistochemistry. Relative GST-pi expression (tumor/mucosa) ranged from 0.31 to 1.52 (0.821 +/- 0.40: mean +/- SD), and only 6 out of 17 cases demonstrated increased GST-pi transcripts in tumor tissue over normal tissue. In situ hybridization and immunohistochemistry showed that morphologically normal esophageal mucosa, especially in its basilar two thirds, expressed the enzyme as strongly as did carcinoma cells. No significant correlation was observed between the amount or pattern of GST-pi expression by carcinomas and the clinicopathological findings in the cases. The marked expression of GST-pi by non pathologic mucosa obtained from the patients with esophageal carcinoma suggests that GST-pi may be a marker of increased carcinogen exposure, but not necessarily a marker of developed human esophageal cancer. PMID- 8517649 TI - Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cells in vitro and in vivo. AB - The modulating effect of human fibroblast-derived interferon beta (IFN-beta) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells in vitro and in vivo was investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2H tetrazolium bromide (MTT) assay was carried out in vitro using the cultured human colon cancer cell line C-1. IFN-beta at concentrations of 50, 500, 5,000 and 50,000 IU/ml was added to the cultured tumor cells with or without 5-FU at concentrations of 10, 50 and 500 micrograms/ml. The antitumor activity of 5-FU with or without IFN-beta was assessed using Co-4, a human colon carcinoma xenograft in nude mice, with reference to thymidylate synthetase inhibition. IFN beta was administered subcutaneously daily for 14 days at doses of 6,000, 60,000 and 600,000 IU/mouse. The combined antitumor effect with 5-FU was evaluated by simultaneous intraperitoneal administration of 5-FU at doses of 10 and 20 mg/kg daily for 10 days. The antitumor activity of IFN-beta alone increased in a dose dependent manner against Co-4 in nude mice, whereas its antitumor activity in vitro against C-1 was limited. The synergistic effect of 5-FU and IFN-beta was observed both in vitro and in vivo, and the in vivo synergism was obtained without any enhancement of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. These results suggest that the mechanism of the combined effect of 5-FU and IFN-beta is not related to enhancement of thymidylate synthetase inhibition or the host immune system, since human fibroblastoid IFN-beta is species-specific to humans. The clinical usefulness of this combination method for the treatment of advanced colorectal carcinoma is expected. PMID- 8517650 TI - Phase II-study for treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. AB - 25 consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB-subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12h days 1-6) and AMSA (120 mg/m2 i.v. days 5 7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h days 1-4 and AMSA 120 mgm2 day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), in 10 after 1 cycle of induction and in 2 after 2 cycles. 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. 9 patients remained refractory (36%) and 4 died during hypoplasia (16%) Median DFS of the 12 responders was 2.9 months and median survival from time of CR 8.9 mo. Median overall survival of responders and non-responders was 6 mo from time of resistance. The survival advantage of responding patients (n = 12) as compared to non-responders (n = 13) was 10.7 vs. 3.2 mo (p = 0.002). Toxicity of chemotherapy was acceptable. 1 patient experienced pulmonary edema due to ara C, 2 patients developed life threatening systemic fungal infections, one of whom died while in CR. PMID- 8517651 TI - 6-Hydroximinoandrostenedione, a new specific inhibitor of estrogen biosynthesis and its effect on T47D human breast cancer cells. AB - A new male steroid hormone analogue, 6-hydroximinoandrostenedione, was obtained in 12% yield by an 8-step synthesis. The compound is cytochrome P450 aromatase specific, inducing a Type-1 optical difference spectrum with the human placental enzyme (Ks 2.24 microM). It efficiently inhibits human cytochrome P450 aromatase (Ki 0.08 microM) in a time--and concentration--dependent manner, but no conclusive evidence was found that it also inactivates the placental enzyme. Cultured human T47D breast cancer cells have the unique capacity to convert de novo [14C]androstenedione into radioactive estrone and estradiol, as we have established by repetitive HPLC purifications of the biosynthetic products formed. A very small amount of an unidentified radioactive metabolite was also formed. We conclude that an endogenous androgen - aromatizing enzyme is present in T47D cells; a fact not previously reported for this human breast cancer cell line. Furthermore, the new aromatase inhibitor was found to cause a significant decrease in the growth of these cells. Our results indicate that: 1) growth of T47D cancer cells is estrogen-dependent, 2) substitution at the C-6 "front" face of an androst-4-ene-3-one molecule does not cause rejection of the modified C19 male steroidhormone by the aromatase enzyme, 3) the new 6 hydroximinoandrostenedione inhibitor has the potential to act as a highly specific anti-aromatase breast cancer agent. PMID- 8517652 TI - Effects of beta-carotene-rich algae Dunaliella bardawil on the dynamic changes of normal and neoplastic mammary cells and general metabolism in mice. AB - As a possible step to estimate the mechanism of the inhibitory role of Dunaliella bardawil (Db) in the initial progression of spontaneous mammary tumours of SHN virgin mice, the DNA synthesizing enzyme activities and the in vivo 31P-NMR spectroscopy of normal and neoplastic mammary cells were examined in mice fed Db. The blood levels of glucose and free fatty acids and 1H-NMR spectroscopy of serum or urine were also studied in these animals to check the general metabolic background. Beginning at 4 months of age, the experimental and the control mice were given a vitamin A deficient AIN-76TM diet supplemented with Db (the concentration of beta-carotene was 5.1 x 10(-5)%) and AIN-76TM diet containing retinyl palmitate (2.2 x 10(-4)%), respectively, until 3 weeks after mammary tumour appearance (tumourous) or 9 months of age (non-tumourous). An increasing rate of thymidine kinase activity in mammary tumour was decreased by Db, while the thymidylate synthetase activity was affected little by the treatment. Lipid synthesis was accelerated by Db in normal mammary cells; however, no difference was observed between the experimental and the control groups in energy and lipid metabolism of mammary tumour cells. The growth of preneoplastic mammary hyperplastic alveolar nodules was also enhanced by Db. Db prevented an increase of blood levels of glucose and free fatty acids and a decrease of cholin plus phosphorylcholin level after tumour appearance. Liver weights of mice given Db were greater than those of the control in both the tumourous and non-tumourous groups. Db had little effect on the urinary component levels before and after the appearance of mammary tumours. These results indicate that Db promotes the growth of normal mammary gland cells, but inhibits that of neoplastic cells, and that the inhibitory effect of Db on mammary tumour progression is due to its normalizing both the organ specific and the general metabolism. PMID- 8517653 TI - Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination. AB - The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6 phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis. PMID- 8517654 TI - Effects of structural modifications of ether lipids on antiproliferative activity against human glioma cell lines. AB - The effect of structural modifications of ether lipids on antiproliferative activity was studied in four human glioma cell lines. Drug potency, determined by microtetrazolium assay, varied 7- to 30-fold. CP 46,665 was most potent; Amido-18 OEt was least potent. Antiproliferative activity was highly dependent on drug exposure time. Except for CP 46,665, which reached maximal activity after 2 hr, 40 microM ether lipids were effective only after 24 hr. Structural modifications of ether lipids can increase their potency and reduce the time required for antiproliferative activity. Ether lipid analogs may be useful for treating human gliomas. PMID- 8517655 TI - Suppression of HL-60 cell proliferation by deferoxamine: changes in c-myc expression. AB - Deferoxamine, an iron chelating agent, inhibits growth of HL-60 cells in a dose dependent fashion. This inhibition of proliferation was completely blocked by simultaneous addition of equal molar FeCl3, and FeCl3 added after 24 hours of deferoxamine treatment was also effective. After 48 hrs, however, the delayed addition failed to reverse growth inhibition by deferoxamine. We showed that deferoxamine-treated HL-60 cells become arrested in S phase rather than at G1/0 phase. Changes in c-myc expression were examined in these deferoxamine-treated cells. A rapid decline of c-myc RNA expression was followed by increased expression (1.6-fold over untreated controls). Similar results were obtained when the expression of c-myc protein was evaluated. These changes in c-myc expression may be involved in the growth inhibition of HL-60 cells by deferoxamine. These results are contrasted with the effects of the differentiation inducer, 1 alpha,25(OH)2D3. PMID- 8517656 TI - Environmental pollution and malignant lymphomas: a tentative contribution to geographic pathology. AB - The present study reports of the geographic distribution of 2,878 cases of uniformly classified malignant lymphomas and of 2,349 similar cases from the literature. Data on histological entities are compared with the geographic and socio-economic characteristics of the regions where they preferentially occur. The results provide three patterns in lymphoma distribution: small cell lymphocytic lymphomas are frequent among populations of European extraction and in farming rather than industrial regions. Lymphomas derived from cells of the germinal center are seen preferentially in so-called "underdeveloped countries", and large cell (immunoblastic) lymphomas appear rather characteristic of industrial areas. Besides genetic influences (rare chronic lymphocytic leukemia (CLL) in Asia as compared to Europe), the results suggest environmental cofactors in the pathogenesis of malignant lymphomas. CLL is more frequent in areas with rather low-dose chronic toxic influences such as from the use of fertilizers and pesticides in farming. Germinal center cell lymphomas tend to occur more frequently in countries with nutritional and hygienic deficiencies with frequent infectious diseases. Large cell high malignancy lymphomas apparently prefer highly industrialized regions with pollution of water supplies by more toxic and immunosuppressive substances. PMID- 8517657 TI - Gamma radiation-induced differentiation on human neuroblastoma cells in culture. AB - We have studied the effect of gamma radiation on differentiation in neuroblastoma cell lines AF8 and SJ-N-KP. Growth inhibition and morphological and biochemical differentiation have been examined following radiation exposure to 1-10 Gy. Gamma radiation induced marked growth inhibition and morphological differentiation in a dose-and time-dependent manner in both cell lines, and induced biochemical differentiation in AF8 cells. PMID- 8517658 TI - Bioassay of transforming growth factor-beta activity in acidic protein extracts from primary breast cancer specimens. AB - Acidic protein extracts have been made from breast tumour specimens, collected at the time of primary surgery. The extracts were partially purified by gel filtration and then tested for transforming growth factor-beta activity in a reproducible cell 3H-thymidine incorporation assay. Purified TGF-beta causes a reproducible increase in NRK colony formation and inhibits incorporation of 3H thymidine by mink lung cells. However, some of the breast cancer extracts were stimulatory in the mink lung lung assay implying that a mitogenic factor like epidermal growth factor (EGF) was co-purified. Fourteen out of thirty extracts were scored positive for TGF-beta in the NRK colony forming assay and these tumours presented at an earlier clinical stage and were predominantly well differentiated. PMID- 8517659 TI - Cytogenetic abnormalities in colon cancer patients: a comparison of T- and B lymphocytes. AB - Cytogenetic analysis of peripheral blood lymphocytes of 19 colorectal cancer patients was carried out in short term blood cultures (T-cells) as well as in Epstein-Barr virus transformed B-cell lymphoblastoid cell lines. One hundred Giemsa-banded metaphases from the T lymphocytes and 50 metaphases from the B lymphocytes of each patient were evaluated for cytogenetic abnormalities. Clonality was not observed in every paired sample. Structural and/or numerical aberrations were most frequent in chromosomes #1, #2, #5, #7, #9, #12, #14, #17, #18 and #21. Aberrations among these chromosomes could be observed individually in either of the cultures, which proves that the analysis of both cultures (T and B cells) is complementary to each other. In some cases involving multiple primary cancers it was interesting that the specific chromosomal change, crucial for a particular malignancy, was identified only in the lymphoblastoid cell line analysis. This supports the notion that B-cell analysis can serve as a useful adjunct to the study of short-term blood cultures and also poses a question as to whether the specific chromosomal changes observed in the analysis are confined to the B-cell lineage. PMID- 8517660 TI - Immunomodulation activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines. AB - Some non-differentiation-induction benzo[a]phenothiazines and mutagenic benz[c]acridines more potently inhibited the mitogen-induced blast transformation of human-peripheral blood lymphocytes than differentiation-induction and non mutagenic counterparts and phenothiazines. Differential absorption spectrophotometry revealed tight complex formation between these drugs and bacterial endotoxin or mitogens. All of these compounds only slightly affected antibody dependent cellular cytotoxicity and natural killer cell activity, but significantly inhibited the endotoxin-or heat-killed Staphylococcus aureus induced tumor necrosis factor production by human mononuclear cells. Pretreatment of mice with these drugs protected them from lethal E. coli infection. Quantumchemical analysis suggests a correlation between the biological activity of these compounds and some molecular orbital parameters such as the charge at C7, and the ratio of polar/total surface areas. PMID- 8517661 TI - Osteoblastic metastasis in advanced prostate cancer. AB - Metastatic prostate cancer is unique in its ability to induce the osteoblastic reaction in skeleton. This phenomenon is probably the result of complex paracrine/autocrine cell interaction between prostate cancer cells and bone cells at the metastatic sites. Recently the use of various in vivo and in vitro systems made possible the confirmation of certain cellular interactions that may participate in this process. The role of IGFs/GFBPs, urokinase-type plasminogen activator (uPA), as well as of TGF beta 1 and glucocorticoids is discussed in this review. PMID- 8517662 TI - Uptake and release of radiolabelled monoclonal antibody Po66 by multicellular aggregates obtained from a lung squamous carcinoma cell line. AB - Po66, a monoclonal antibody (MAb) directed against lung squamous cell carcinoma, has been shown, when injected intravenously, to be retained for a long time in tumors. This property encouraged trials to use Po66 as an agent of metabolic radiotherapy. The suitability of multicellular spheroids to reproduce the in vivo conditions of irradiation of tumors by Po66 was investigated in the present work. Spheroids were formed from the lung carcinoma cell line SK-MES-1. They resembled morphologically small carcinoma nodules with desmosome-like intercellular junctions at the periphery and a central necrotic core. The cells expressing the antigen recognized by Po66 had a heterogeneous distribution and were predominant in the outer layers of the cell aggregates. Spheroids were exposed to radiolabelled Po66. The MAb diffused slowly and reached a maximal incorporation after 4-12 hours incubation. A control unrelated antibody did not penetrate appreciably. Autohistoradiographic experiments suggested that the antibody accumulated in most cells expressing the antigen. The rate of MAb release from the spheroids was very low (T 1/2 = 163 h). Taken together, the data indicate that spheroids might be a relevant model to investigate the parameters controlling Po66-mediated immunoradiotherapy. PMID- 8517663 TI - A new technique for detecting fluorescently labelled cells at very low densities. AB - We have developed a new cytometric method that has the potential for detecting fluorescently labelled cells at very low densities against a high density background of non-fluorescing cells of similar size. The method uses a Waveform Analysis Interface which is an electronic device that is essentially an "add-on" to a flow cytometer. It takes the amplified fluorescence and scatter signals from the flow cytometer and measures their intensities at microsecond intervals. It can be programmed to react only to cells with specific characteristics and ignore all others. In this mode it is possible to detect fluorescently labelled cells at densities down to about 1.mL-1 against a background density of non-fluorescent cells of similar size of more than 1 x 10(7).mL-1. This application may have considerable potential for cancer diagnosis and therapy. PMID- 8517664 TI - In vitro evaluation of the differential cytotoxicity of keto-C-glycosides toward normal and malignant cells. AB - In a previous work, we have shown that some members of the family of keto-C glycosides (KCGs) possess interesting biological properties as they exhibited cytotoxic effects at the nanomolar level on malignant cells. In this report, we selected six KCGs in order to investigate their selective cytotoxicity on several malignant epithelial and lymphoblastoid cells, as well as on their normal counterparts. For this purpose, we compared the activities of KCGs upon hepatoma cells and hepatocytes and upon lymphoma cells, normal lymphocytes and bone marrow cells. The tested drugs showed real discriminating cytotoxic effects since the cytotoxicity was several log greater on malignant than on non malignant cells. An in vitro comparative study of KCGs and some conventional chemotherapeutic agents showed that two of them were more potent than 5-fluorouracil, cis-platinum and etoposide. It is interesting to note that KCGs showed very low cytotoxic effects on either murine splenocytes, human peripheral blood lymphocytes or human bone marrow cells, indicating a weak immunosuppressive activity. The results presented here strongly suggest the selective cytotoxic activity of KCGs toward tumoral cells. PMID- 8517665 TI - Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines. AB - The effect of L-ascorbate and its derivatives on the growth of malignant and nonmalignant cell lines has been examined. L-Ascorbate and its oxidative product dehydroascorbate were cytotoxic or lethal to the fast-growing malignant cells, but they were less toxic to nonmalignant cells. Two isomers of ascorbate, D ascorbate and D-isoascorbate, both with 5% of the antiscorbutic potency and very high turnover rate, had similar activities. The cytotoxic effect of ascorbate was apparently not related to the metabolic or vitamin activities of ascorbate at the cellular level. Furthermore, studies on the viability of treated cells indicated that the observed effect on cell growth was not cytostatic in nature but was the result of a direct cell-killing action of ascorbate. Several groups of ascorbate derivatives were also tested; many of them were toxic to these cells. The results support the hypothesis that the cytotoxic activity of ascorbate was due to its chemical properties and that certain oxidation and degradation products of ascorbate were cytotoxic agents. PMID- 8517666 TI - mdr 1 gene-expression and villin synthesis in a colon cancer cell line differentiated by sodium butyrate. AB - Sodium butyrate (NaBu) but not dimethylsulfoxide (DMSO) induced the synthesis of villin, a protein of the brush border microvilli cytoskeleton, in a rat colon cancer cell line. Neither NaBu nor DMSO altered mdr 1-mRNA expression or multidrug resistance (MDR)--associated cellular transport of doxorubicin. These results show that mdr 1 gene expression and activity are independent of other brush border proteins induced by differentiating agents at the apical pole of the epithelial cell. PMID- 8517667 TI - Modulation of B16-BL6 murine melanoma metastatic phenotype by tyrosine and phenylalanine restriction in the absence of host selection pressures. AB - We previously showed that restriction of tyrosine (Tyr) and phenylalanine (Phe) in vivo dramatically suppresses the metastatic phenotype of B16-BL6 (BL6) murine melanoma. Present results indicate a direct effect of Tyr and Phe restriction on the tumor in the absence of host selection pressures. Lung colonizing ability of BL6 is dramatically suppressed after one passage in vitro in media containing low levels of Tyr and Phe. This antimetastatic effect is immediate, stable for at least 5 in vitro passages in Tyr and Phe restricted media, and evident event after levels of Tyr and Phe are restored to normal. Heterogeneity for lung colonizing ability is suppressed, as evidence by fewer tumor colonies formed by clones following i.v. inoculation into mice fed normal diet. This suppression of BL6 metastatic phenotype is not due to differential clearance and retention in the lung or to decreased growth, but is specific for these two amino acids. As the mechanism(s) for the antitumor effects of Tyr and Phe restriction are detailed, the relevance of Tyr and Phe restriction as an early adjuvant to effective cancer treatment can be explored. PMID- 8517668 TI - Stereologically measured nuclear volume in comparison to two-dimensional nuclear morphometry, mitotic index and flow cytometry in predicting disease outcome in bladder cancer. AB - The prognostic value of stereologically estimated nuclear volume was compared to the prognostic value of clinical, histological, morphometric and flow cytometric prognostic factors in a cohort of 212 patients followed up for over 11 years. T category (p = 0.014), grade (p < 0.0001), papillary status (p = 0.001), nuclear area (p < 0.0001), SD of nuclear area (p < 0.0001), DNA ploidy (p < 0.0001), S phase fraction (p < 0.0001), mitotic index (p < 0.0001) and nuclear volume were significantly interrelated. Progression in T- (p = 0.090), N- (p = 0.007) and M categories (p = 0.001) was related to nuclear volume, while independent predictors of progression in a multivariate analysis were grade and S phase fraction. Nuclear volume predicted survival in the entire cohort (p = 0.0004) and in papillary tumours (p = 0.0048), whereas in superficial tumours it had no prognostic value. In multivariate survival analysis T-category (p < 0.001), papillary status (p < 0.001) and S phase fraction (p = 0.011) predicted survival and S phase fraction predicted (p = 0.052) recurrence-free survival in Ta-T1 tumours. The results suggest that stereological measurement of nuclear volume provides no additional prognostic information over proliferation indices (mitotic index, S phase fraction) in bladder cancer. PMID- 8517669 TI - A comparative study of the anticancer efficacy of doxorubicin carrying microspheres and liposomes using a rat liver tumour model. AB - Due to low efficacy of chemotherapy in the treatment of liver cancer, several methods of drug targeting have been investigated. Liposomes designed to carry cytotoxic drugs to the liver are currently under clinical evaluation. While experimental evidence shows promise, this method of drug delivery has several disadvantages that include short shelf life and poor drug delivery into tumour tissue. An alternative strategy for targeted drug delivery involving use of ion exchange microspheres may overcome these limitations while still reducing systemic toxicity and maintaining therapeutic efficacy. The purpose of this study was to determine the relative antitumour efficacy of these two drugs carrying systems in the treatment of liver cancer. Compared to controls, DOX treatment with free drug, liposomes or microspheres significantly reduced tumour growth by 56% (P < 0.001), 51% (P < 0.01) and 79% (P < 0.001) respectively. Furthermore, the DOX-microsphere treatment was significantly better than either of the other DOX treatments (53%, P < 0.05) or the sham-microsphere treated group (64%, P < 0.05). Thus, drug microspheres can increase the anti-tumour efficacy compared to either free or liposomal drug while simultaneously reducing systemic toxicity. PMID- 8517670 TI - Quantitative cerebrospinal fluid cytology in patients receiving intracavitary chemotherapy. AB - Cytological evaluation of cerebrospinal fluid (CSF) is an important means of following response to intracavitary chemotherapy for leptomeningeal malignancy. We studied the feasibility of quantitative cytological evaluation by retrospective analysis of serial CSF specimens from 7 patients receiving phase I intracavitary chemotherapy for leptomeningeal malignancy who had persistent malignant cytology. Three to 34 CSF specimens per patient obtained over a 3- to 48-week period were reviewed. Significant (five- to 10-fold or greater) reductions in numbers of malignant cells in CSF during treatment could be identified in specimens otherwise diagnosed as positive. Quantitative CSF cytological evaluation is neither overly time consuming nor tedious to perform and may provide useful clinical information. PMID- 8517671 TI - Shared T-cell receptor gene usage in experimental allergic neuritis and encephalomyelitis. PMID- 8517672 TI - Cerebrospinal fluid choline levels in Parkinson's disease. PMID- 8517673 TI - Transfer of multiple sclerosis into severe combined immunodeficiency mice. PMID- 8517674 TI - Noninvasive diagnosis of the MELAS syndrome from blood DNA. PMID- 8517675 TI - Spinal fluid lymphocytes from a subgroup of multiple sclerosis patients respond to mycobacterial antigens. AB - Immune responses to heat shock or stress proteins are observed in several chronic autoimmune diseases. Such proteins are major antigens of many bacteria, especially mycobacteria. To determine whether immune responses to stress proteins occur in chronic inflammatory diseases of the central nervous system such as multiple sclerosis (MS) we measured proliferative responses of lymphocytes from spinal fluids and bloods of patients with MS and other neurological diseases to a sonicate of M. tuberculosis, an acetone extract of M. tuberculosis, a recombinant 65-kd heat shock protein of M. leprae, and tetanus toxoid as a control recall antigen. Significantly increased spinal fluid lymphocyte responses to mycobacterial sonicate, relative to responses from paired peripheral blood lymphocytes, were present in 14 of 20 specimens from patients with MS (p < 0.025) and 2 of 9 specimens from patients with other neurological diseases. Spinal fluid lymphocytes also responded to tetanus toxoid, but differences between blood and spinal fluid were not statistically significant. Lymphocytes from 1 patient with MS responded only to M. leprae. There were no proliferative responses to the M. tuberculosis acetone extract. When patients with MS were classified according to duration of disease (< 2- or > 2-yr duration) 9 of 10 patients with recent onset had cerebrospinal fluid cells that responded to M. tuberculosis compared with 5 of 10 with longer duration symptoms (p < 0.012). Our data suggest a selective recruitment and/or expansion of mycobacterial reactive cells to the central nervous system of a subpopulation of patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517677 TI - Gene therapy for Duchenne dystrophy. PMID- 8517676 TI - Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological, and genetic observations. AB - We reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged-red fibers. In patients with earlier onset of symptoms (< 2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine-like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged-red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. PMID- 8517678 TI - Modulation of motor cortical outputs to the reading hand of braille readers. AB - We used focal transcranial magnetic stimulation to map the motor cortical areas targeting the first dorsal interosseous and the abductor digiti minimi muscles bilaterally in 10 proficient braille readers and 10 blind controls who were matched for age (mean, 50.6 yr) and age at time of blindness (mean, 7.5 yr). The proficient braille readers had learned braille at age 8 to 14 years and used it daily for 5 to 10 hours. Controls had not learned braille until age 17 to 21 years and used it daily for < 1 hour. In the controls, motor representations of the right and left first dorsal interosseous and abductor digiti minimi muscles were not significantly different. However, in the proficient braille readers, the representation of the first dorsal interosseous muscle in the reading hand was significantly larger than that in the nonreading hand or in either hand of the controls. Conversely, the representation of the abductor digiti minimi muscle in the reading hand was significantly smaller than that in the nonreading hand or in either hand of the controls. These differences were not due to differences in motor thresholds. Our results suggest that the cortical representation of the reading finger in proficient braille readers is enlarged at the expense of the representation of other fingers. PMID- 8517679 TI - The human-severe combined immunodeficiency myasthenic mouse model: a new approach for the study of myasthenia gravis. AB - We have established a new chimeric human-mouse model of myasthenia gravis in severe combined immunodeficiency mice, using human peripheral blood lymphocytes that survive in the mouse and produce specific antibodies that mediate pathological changes typical of human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti-acetylcholine receptor (AChR) antibody-positive and -negative patients with myasthenia gravis showed circulating anti acetylcholine receptor antibodies, deposition of human IgG at muscle end-plates, and simplification of the postsynaptic membrane, findings characteristic of human myasthenia gravis. Mice given human peripheral blood lymphocytes from healthy donors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells to reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune regulation in autoimmunity. PMID- 8517680 TI - Heat-shock proteins and autoimmunity: implications for multiple sclerosis. PMID- 8517681 TI - Heterogeneity of autoantibodies in stiff-man syndrome. AB - Stiff-man syndrome is a rare neurological disorder characterized by skeletal muscle rigidity and spasms in which detection of circulating anti-glutamic acid decarboxylase antibodies has suggested an autoimmune pathogenesis. To further define the role of autoimmunity in the pathogenesis, we studied anti-glutamic acid decarboxylase antibodies, as well as organ- and non-organ-specific autoantibodies in 13 patients with stiff-man syndrome and 127 patients with other neurological disorders. Thyrogastric antibodies were more frequent in patients with stiff-man syndrome (46%) than in those with other neurological disorders (12%) (p < 0.05). Non-organ-specific antibodies were found at a similar frequency in the patients with stiff-man syndrome (61%) and those with other neurological disorders (65%). Islet-cell autoantibodies and anti-glutamic acid decarboxylase antibodies were more common in stiff-man syndrome patients (38% and 31%) compared to the patients with other neurological disorders (6% and 3%, respectively; p < 0.001). With the exception of 1 patient in the other neurological disorders group, anti-glutamic acid decarboxylase antibodies were always associated with islet-cell autoantibodies. Four patients with stiff-man syndrome had an associated solid tumor: 3 of them had antibodies recognizing a 125/130-kd protein and not glutamic acid decarboxylase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517682 TI - Diffuse microgliosis associated with cerebral atrophy in the acquired immunodeficiency syndrome. AB - The cause of cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS) is obscure because human immunodeficiency virus type 1 (HIV-1)-related histopathological changes hardly correlate with cerebral atrophy. In this study, brain ventricular expansion was compared to the frontal lobe density of mononuclear and astroglial cells at autopsy. Twenty-eight male patients with AIDS displaying varying degrees of atrophy were compared to 17 age-matched male control subjects without AIDS or atrophy. An index of ventricular expansion was measured in uniformly sliced, formalin-fixed brain specimens, and immunochemically marked cells in coronal sections of the left superior frontal gyrus (Brodmann area 8) were quantified by field counting and planimetry. In the cortex, diffuse ferritin-stained microglia and glial fibrillary acidic protein positive astrocytes were about twice as numerous in the patients with AIDS. Sixty five percent (18/28) of the patients with AIDS had a microglial cell density greater than 2 standard deviations above the control mean. Microglial cell density was correlated positively with the severity of ventricular expansion (r = 0.71, p < 0.0001), while hypertrophied astroglial cells were very weakly related. In white matter, Ham-56-positive macrophages and glial fibrillary acidic protein positive astrocytes were not meaningfully correlated with the index of ventricular expansion. Brain ventricular expansion and diffuse cortical microgliosis are highly prevalent anomalies in patients with AIDS, and their interrelationship may be more important than previously recognized. PMID- 8517683 TI - When does human brain development end? Evidence of corpus callosum growth up to adulthood. AB - To locate structural changes in the brain accounting for the increasing effectiveness in cognition and skills that occurs at the final stage of behavioral development, we attempted to determine the age at which the corpus callosum completes its active growth period. We assessed the growth rate of the corpus callosum by measuring its area twice on midsagittal magnetic resonance imaging scans separated by a 2-year interval, in a series of 90 subjects with a wide range of ages. We observed an increase in the size of the corpus callosum as long as human mentation expands, up to the middle 20s. Clinical and experimental data about the corpus callosum, together with the present findings, suggest that the corpus callosum is part of the highest order-latest maturing neural network of the brain. PMID- 8517684 TI - Myoblast transfer in Duchenne muscular dystrophy. AB - One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent. PMID- 8517685 TI - A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections. AB - The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor. PMID- 8517686 TI - Magnetic resonance imaging of brain and the neuromotor disorder in endemic cretinism. AB - Neurological endemic cretinism, resulting from severe iodine deficiency, is characterized by mental deficiency, deafmutism, and a spastic-rigid motor disorder. Its neuropathology and pathophysiology have been investigated very little. We report the clinical and magnetic resonance imaging brain scan findings of 3 adult Chinese cretins. All show an apparent magnetic resonance imaging abnormality in the globus pallidus and substantia nigra, with hyperintensity on T1-weighted images and hypointensity on T2-weighted images. The motor abnormality, characterized by truncal and proximal limb-girdle rigidity and spasticity, with relative sparing of the hands and feet, is analogous to other extrapyramidal disorders. Endemic cretinism is a unique form of cerebral palsy of potential interest for students of human neuromotor development. PMID- 8517687 TI - The effects of X monosomy on brain development: monozygotic twins discordant for Turner's syndrome. AB - Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal-occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome. PMID- 8517688 TI - Postantibiotic effects of amikacin and ofloxacin on Mycobacterium fortuitum. AB - A study of postantibiotic effects (PAE) in vitro of amikacin and ofloxacin on Mycobacterium fortuitum isolates from sternotomy wounds by use of the dilution method for drug removal showed that both drugs exhibited good bactericidal activities, with the PAE of amikacin lasting from 13.5 to 27.6 h and the PAE of ofloxacin lasting from 1.2 to 5.0 h. These laboratory results concur with our experience of the efficacy of once-daily dosing with these drugs in the treatment of infections caused by M. fortuitum. These data may have therapeutic implications in guiding the scheduling of the administration of drugs in these infections, which require a long duration of therapy. PMID- 8517689 TI - Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy. AB - A nonparametric expectation maximization approach to the study of population pharmacokinetics is described for an aminoglycoside antibiotic. The method is used to explore population estimates for gentamicin clearance (liters per hour per creatinine clearance) and volume of distribution (liters per kilogram) in tumor patients. Joint and marginal probability distributions are plotted and further characterized by using standard descriptors such as mean, median, mode, standard deviation, skewness, and kurtosis. Results of additional analyses using hematologic or solid tumor subpopulations agree with those of a recent larger study which found no significant pharmacokinetic differences between these groups. Nonparametric maximum-expectation analyses are convenient and allow exploratory analysis of population estimates directly from routine laboratory information. PMID- 8517690 TI - Genetic and biochemical analysis of a novel Ambler class A beta-lactamase responsible for cefoxitin resistance in Bacteroides species. AB - A clinical isolate of Bacteroides vulgatus was resistant to tetracycline, clindamycin, ampicillin, cephaloridine, cefoxitin, and other beta-lactam antibiotics except imipenem. beta-Lactam resistance was mediated by a membrane associated, clavulanate-sensitive cephalosporinase capable of degrading cephalosporins and penicillins. Cefoxitin also was degraded but at a slow rate. The cefoxitin resistance (Fxr) determinant was cloned from B. vulgatus genomic libraries that were prepared in Escherichia coli and then mated with Bacteroides fragilis for the identification of Fxr strains. Analysis of B. fragilis strains with the cloned Fxr determinant revealed the presence of a new beta-lactamase protein with the physical and enzymatic properties of the beta-lactamase found in the original B. vulgatus isolate. The beta-lactamase gene (cfxA) was subcloned on a 2.2-kb DraI-HindIII fragment, and the nucleotide sequence was determined. These results showed that cfxA encoded a protein of 321 amino acids and 35,375 molecular weight. Mutant strains in which the cfxA structural gene was disrupted by insertional inactivation lost both Fxr and beta-lactamase activity. Comparison of CfxA with other beta-lactamases showed a relationship with the active-site serine beta-lactamases in the Ambler molecular class A, although CfxA had apparently diverged significantly. This was exemplified by the substitution in CfxA at 13 of 25 amino acid residues previously identified as being invariant in class A beta-lactamases. These results suggest that CfxA may represent a new class A homology group which diverged very early. PMID- 8517691 TI - Carnitine status and safety after administration of S-1108, a new oral cephem, to patients. AB - The metabolism and clinical safety of the pivalic acid-containing antibiotic S 1108, an orally active pro-drug cephalosporin, were investigated to assess the clinical effects, with special emphasis on the influence of carnitine consumption in 15 patients with various infectious diseases receiving S-1108 three times a day at a 300- or 600-mg total daily dose for 3 to 7 days. The free carnitine concentrations in plasma were greatly reduced to approximately 65% of pretreatment levels, and the plasma pivaloylcarnitine (the main metabolite of pivaloyloxymethyl ester) concentrations were increased during the 200-mg (three times a day) regimens but returned to the pretreatment levels within 3 to 5 days after the cessation of treatment. In three elderly patients with declining renal function (creatinine clearance rate, 31 to 50 ml/min), the acylcarnitine/free carnitine ratio increased from 0.1 to 0.4 up to 0.7 to 1.5 at day 5 during the 7 day treatment, showed a tendency to decrease, and then returned to the pretreatment ratio 4 days after discontinuation of the drug. The degree of free carnitine reduction and increase of the acylcarnitine/free carnitine ratio depended mostly on the dose and the duration of S-1108 treatment. The increased acylcarnitine/free carnitine ratio in elderly patients was due to reduction of the free carnitine concentration in plasma and mainly to the retardation of nontoxic pivaloylcarnitine excretion. This study indicated that there was a decrease in free carnitine levels in plasma, but there were no clinical symptoms or adverse effects associated with carnitine reduction in patients during the 7 day multiple administration of S-1108. PMID- 8517692 TI - Pyrimethamine inhibits renal secretion of creatinine. AB - The mechanism of increased serum creatinine after administration of pyrimethamine and dapsone was evaluated for six healthy volunteers. Serum parameters, urine sediment, and clearances of creatinine, inulin, and para-aminohippurate were assessed prior to and 28 h after the ingestion of a single, combined dose of 100 mg of pyrimethamine and 200 mg of dapsone. In a second series, the same renal function tests were performed for nine human immunodeficiency virus-infected men before and after 1 month of prophylactic treatment with a weekly dose of 75 mg of pyrimethamine and 200 mg of dapsone to evaluate sustained effects on renal function. Serum creatinine increased within 28 h from 81 +/- 14 to 102 +/- 16 mumol/liter (P = 0.002) in the healthy volunteers. Blood urea nitrogen, beta 2 microglobulin, and urine remained normal. Creatinine clearance decreased from 125 +/- 27 to 91 +/- 26 ml/min (P < 0.02) without changes in inulin clearance. The effect was reversible within 21 days and attributable to pyrimethamine, as determined by administration of each drug alone. The sustained effect of four doses of pyrimethamine and dapsone in human immunodeficiency virus-infected patients consisted of an analogous rise in serum creatinine from 69 +/- 17 to 87 +/- 32 mumol/liter (P < 0.05). Both creatinine and inulin clearances, however, were unchanged, representing a new equilibrium between creatinine production and elimination at a higher level in serum. Pyrimethamine, thus, may reversibly inhibit renal tubular secretion of creatinine without affecting the glomerular filtration rate. This physiologic effect in pyrimethamine-treated patients must be differentiated from possible organ-related nephropathies. PMID- 8517693 TI - Development of a population pharmacokinetic model and optimal sampling strategies for intravenous ciprofloxacin. AB - Data obtained from 74 acutely ill patients treated in two clinical efficacy trials were used to develop a population model of the pharmacokinetics of intravenous (i.v.) ciprofloxacin. Dosage regimens ranged between 200 mg every 12 h and 400 mg every 8 h. Plasma samples (2 to 19 per patient; mean +/- standard deviation = 7 +/- 5) were obtained and assayed (by high-performance liquid chromatography) for ciprofloxacin. These data and patient covariates were modelled by iterative two-stage analysis, an approach which generates pharmacokinetic parameter values for both the population and each individual patient. The final model was used to implement a maximum a posteriori-Bayesian pharmacokinetic parameter value estimator. Optimal sampling theory was used to determine the best (maximally informative) two-, three-, four-, five-, and six sample study designs (e.g., optimal sampling strategy 2 [OSS2] was the two-sample strategy) for identifying a patient's pharmacokinetic parameter values. These OSSs and the population model were evaluated by selecting the relatively rich data sets, those with 7 to 10 samples obtained in a single dose interval (n = 29), and comparing the parameter estimates (obtained by the maximum a posteriori Bayesian estimator) based on each of the OSSs with those obtained by fitting all of the available data from each patient. Distributional clearance and apparent volumes were significantly related to body size (e.g., weight in kilograms or body surface area in meters squared); plasma clearance (CLT in liters per hour) was related to body size and renal function (creatinine clearance [CLCR] in milliliters per minute per 1.73 m2) by the equation CLT = (0.00145.CLCR + 0.167).weight. However, only 30% of the variance in CLT was explained by this relationship, and no other patient covariates were significant. Compared with previously published data, this target population had smaller distribution volumes (by 30%; P < 0.01) and CLT (by 44%; P < 0.001) than weight- and CLCR- matched stable volunteers. OSSs provided parameter estimates that showed good to excellent estimates of CLT (or area under the concentrations-time curve [AUC]) were unbiased and precise (e.g., r2 for AUC for all data versus AUC for OSS2 was > 0.99) and concentration-time profiles were accurately reconstructed. These results will be used to model the pharmacodynamic relationships between ciprofloxacin exposure and response and to aid in developing algorithms for individual optimization of ciprofloxacin dosage regimens. PMID- 8517694 TI - Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. AB - Seventy-four acutely ill patients were treated with intravenous ciprofloxacin at dosages ranging between 200 mg every 12 h and 400 mg every 8 h. A population pharmacokinetic-pharmacodynamic analysis relating drug exposure (and other factors) to infectious outcome was performed. Plasma samples were obtained and assayed for ciprofloxacin by high-performance liquid chromatography. Samples from patients were frequently cultured so that the day of bacterial eradication could be determined. The pharmacokinetic data were fitted by iterative two-stage analysis, assuming a linear two-compartment model. Logistic regression was used to model ciprofloxacin exposure (and other potential covariates) versus the probabilities of achieving clinical and microbiologic cures. The same variables were also modelled versus the time to bacterial eradication by proportional hazards regression. The independent variables considered were dose, site of infection, infecting organism and the MIC for it, percent time above the MIC, peak, peak/MIC ratio, trough, trough/MIC ratio, 24-h area under the concentration time curve (AUC), AUC/MIC ratio (AUIC), presence of other active antibacterial agents, and patient characteristics. The most important predictor for all three measures of ciprofloxacin pharmacodynamics was the AUIC. A 24-h AUIC of 125 SIT 1.h (inverse serum inhibitory titer integrated over time) was found to be a significant breakpoint for probabilities of both clinical and microbiologic cures. At an AUIC below 125 (19 patients), the percent probabilities of clinical and microbiologic cures were 42 and 26%, respectively. At an AUIC above 125 (45 patients), the probabilities were 80% (P < 0.005) and 82% (P < 0.001), respectively. There were two significant breakpoints in the time-to-bacterial eradication data. At an AUIC below 125 (21 patients), the median time to eradication exceeded 32 days; at an AUIC of 125 to 250 (15 patients), time to eradication was 6.6 days: and at AUIC above 250 (28 patients), the median time to eradication was 1.9 days (groups differed; P < 0.005). These findings, when combined with pharmacokinetic data reported in the companion article, provide the rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities. An a priori dosing algorithm (based on MIC, patient creatine clearance and weight, and the clinician-specified AUIC target) was developed. This approach was shown, retrospectively, to be more precise than current guidelines, and it can be used to achieve more rapid bacteriologic and clinical responses to ciprofloxacin, as a consequence of targeting the AUIC. PMID- 8517695 TI - N-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity in vitro and in vivo. AB - On the basis of our previous demonstration of the high inhibitory activity of a series of p-n-alkyloxybenzhydroxamic acids and n-alkyl esters of 3,4 dihydroxybenzoic acid against the trypanosome alternative oxidase in a cell-free mitochondrial preparation of Trypanosoma brucei brucei, we synthesized a series of N-n-alkyl-3,4-dihydroxybenzamides for evaluation as inhibitors of this enzyme. This class of compounds was selected with the expectation of their having similar inhibitory activity to but greater solubility than the esters and hydroxamic acids noted above and greater resistance to serum hydrolases in vivo. We predicted that such properties would allow an inhibitor of the trypanosome alternative oxidase to be coadministered with glycerol as a means of providing treatment for infections by African trypanosomes. As expected, such benzamides were both more soluble and more stable, some being more active against the target enzyme than the corresponding ester. One, N-n-butyl-3,4-dihydroxybenzamide, was selected for evaluation in vivo against T. brucei brucei. When combined with glycerol, this benzamide was found to be curative. A regimen wherein 450 mg of N n-butyl-3,4-dihydroxybenzamide per kg and 15 g of glycerol per kg were given hourly in three divided doses cured 17 of 19 mice with established T. brucei brucei infections. This combination is more active in vivo than any other designed to block simultaneously both the unique respiratory electron transport system and the anaerobic glycolytic pathways of these pathogenic protozoa. PMID- 8517696 TI - Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. AB - Transport processes are used by all organisms to obtain essential nutrients and to expel wastes and other potentially harmful substances from cells. Such processes are important means by which resistance to selected antimicrobial agents in bacteria is achieved. The recently described Staphylococcus aureus norA gene encodes a membrane-associated protein that mediates active efflux of fluoroquinolones from cells. SA-1199B is a fluoroquinolone-resistant strain of S. aureus from which we cloned an allele of norA (norA1199). Similar to that of norA, the protein product of norA1199 preferentially mediates efflux of hydrophilic fluoroquinolones in both S. aureus and an Escherichia coli host, a process driven by the proton motive force. Determination of the nucleotide sequence of norA1199 revealed an encoded 388-amino-acid hydrophobic polypeptide 95% homologous with the norA-encoded protein. Significant homology with other proteins involved in transport processes also exists, but especially with tetracycline efflux proteins and with the Bacillus subtilis Bmr protein that mediates active efflux of structurally unrelated compounds, including fluoroquinolones. In S. aureus, the norA1199-encoded protein also appears to function as a multidrug efflux transporter. Southern hybridization studies indicated that norA1199 (or an allele of it) is a naturally occurring S. aureus gene and that related sequences are present in the S. epidermidis genome. The nucleotide sequence of the wild-type allele of norA1199, cloned from the fluoroquinolone-susceptible parent strain of SA-1199B, did not differ from that of norA1199 throughout the coding region. Northern (RNA) and Southern hybridization studies showed that increased transcription, and not gene amplification, of norA1199 is the basis for fluoroquinolone resistance in SA 1199B. PMID- 8517697 TI - Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group. AB - A standardized antiviral drug susceptibility assay for clinical human immunodeficiency virus type 1 (HIV-1) isolates has been developed for use in clinical trials. The protocol is a two-step procedure that first involves cocultivation of patient infected peripheral blood mononuclear cells (PBMC) with seronegative phytohemagglutinin-stimulated donor PBMC to obtain an HIV-1 stock. The virus stock is titrated for viral infectivity (50% tissue culture infective dose) by use of serial fourfold virus dilutions in donor PBMC. A standardized inoculum of 1,000 50% tissue culture infective doses per 10(6) cells is used in the second step of the procedure to acutely infect seronegative donor PBMC in a 7 day microtiter plate assay with triplicate wells containing zidovudine (ZDV) concentrations ranging from 0 to 5.0 microM. The ZDV 50% inhibitory concentrations (IC50) for reference ZDV-susceptible and ZDV-resistant HIV-1 isolates ranged from 0.002 to 0.113 microM and from 0.15 to > 5.0 microM, respectively. Use of this consensus protocol reduced interlaboratory variability for ZDV IC50 determinations with reference HIV-1 isolates. Among eight laboratories, the coefficient of variation ranged from 0.85 to 1.25 with different PBMC protocols and was reduced to 0.39 to 0.98 with the standardized assay. Among the clinical HIV-1 isolates assayed by the standardized drug susceptibility assay, the median ZDV IC50 increased gradually with more ZDV therapy. This protocol provides an efficient and reproducible means to assess the in vitro susceptibility to antiretroviral agents of virtually all clinical HIV-1 isolates. PMID- 8517698 TI - Clonal viability measurements on Plasmodium falciparum to assess in vitro schizonticidal activity of leupeptin, chloroquine, and 5-fluoroorotate. AB - Until now, the in vitro activity of potential antimalarial agents has been evaluated primarily by monitoring decreases in parasite proliferation. These traditional assays do not distinguish between compounds that arrest proliferation of parasites and compounds that kill them. In this report, a more complex in vitro cytocidal assay for Plasmodium falciparum is described. This assay measures the clonal viability of P. falciparum after the parasites have been treated with an antimalarial agent. The new assay was used to assess cytocidal activities of three antimalarial agents that work through unrelated mechanisms. Leupeptin, a protease inhibitor, arrested the proliferation of W2 clones of P. falciparum at a MIC of 50 microM, but at least 80% of leupeptin-treated cells were viable as judged by the cytocidal assay. On the other hand, chloroquine at 1 microM, its MIC for W2 cells, not only arrested parasite proliferation but also killed more than 99% of the cells. Earlier studies had shown that treatment of P. falciparum with 100 nM 5-fluoroorotate for 48 h was sufficient to inhibit parasite proliferation and parasite thymidylate synthase but not enough to cause significant incorporation of 5-fluoropyrimidines in parasite nucleic acids. By using the new schizonticidal assay, these conditions were found to be necessary and sufficient to kill all parasites in culture. Results of these studies are consistent with the hypothesis that 5-fluoroorotate-based inactivation of P. falciparum thymidylate synthase triggers a lethal mechanism against malarial parasites. PMID- 8517699 TI - Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu). AB - Artemisinin is an important new antimalarial agent containing a bridged endoperoxide. The in vitro antimalarial activity of an artemisinin derivative, arteether, is antagonized by two iron chelators, pyridoxal benzoylhydrazone and 1,2-dimethyl-3-hydroxypyrid-4-one. Similarly, the acute toxicity of artemisinin in mice is antagonized by another chelator, deferoxamine-hydroxyethylstarch. A combination of artemisinin and hemin oxidizes erythrocyte membrane thiols in vitro, and this oxidation is also inhibited by an iron chelator. Thus, iron plays a role in the mechanisms of action and toxicity of artemisinin. The combination of artemisinin and hemin also decreases erythrocyte deformability. Iron probably catalyzes the generation of free radicals from artemisinin since alpha-tocopherol antagonizes the thiol-oxidizing activity of artemisinin and since a spin-trapped free radical signal can be seen by electron paramagnetic resonance only when artemisinin is incubated in the presence of iron. PMID- 8517701 TI - Activity of pirlimycin against pathogens from cows with mastitis and recommendations for disk diffusion tests. AB - Pirlimycin is an analog of clindamycin that will be recommended for therapy of bovine mastitis. It has good activity against staphylococci and streptococci, the major pathogens for bovine mastitis. Five hundred and thirty bacterial isolates recovered from cows with mastitis were studied to confirm the spectrum of activity and to develop recommendations for susceptibility testing. Pirlimycin is not active against isolates of Enterobacteriaceae, it varies in its activity against enterococci, and it is active against veterinary isolates of streptococci (MIC for 50% of strains tested, < or = 0.03 to 0.06 microgram/ml) and staphylococci (MIC for 50% of strains tested, 0.25 to 1.0 microgram/ml). On the basis of levels of drug attained in the milk with recommended dosing schedules, we chose MIC breakpoints of < or = 2 micrograms/ml for susceptibility and > or = 4 micrograms/ml for resistance. We also recommended a disk diffusion test using a disk containing 2 micrograms/ml and breakpoints of < or = 12 mm for resistance and > or = 13 mm for susceptibility. PMID- 8517700 TI - In vitro activity of vancomycin against the spirochete Borrelia burgdorferi. AB - Borrelia burgdorferi, a spirochete and the causative agent of Lyme disease, has been reported to be susceptible to a variety of antimicrobial agents. In this investigation, the action of vancomycin, a glycopeptide antibiotic not previously known to have activity against spirochetes, against borrelias was examined. The in vitro activity of vancomycin against a variety of strains of B. burgdorferi and one strain of Borrelia hermsii was determined by use of a microdilution MIC method (L.L. Dever, J.H. Jorgensen, and A.G. Barbour, J. Clin. Microbiol. 30:2692 2697, 1992). MICs ranged from 0.5 to 2 micrograms/ml. MICs of the glycopeptides ristocetin and teicoplanin and the lipopeptide daptomycin against strain B31 of B. burgdorferi were all > or = 8 micrograms/ml. Subsurface plating, time-kill studies, synergy studies, and electron microscopy were used to investigate further the activity of vancomycin against B31. The MBC of vancomycin was 2 micrograms/ml. Time-kill curves demonstrated > or = 3-log10-unit (99.9%) killing of the final inoculum after 72 h by vancomycin concentrations twice the MIC. Synergy between vancomycin and penicillin was demonstrated at concentrations one fourth the MIC of each drug. In electron microscopy, B31 cells exposed to vancomycin showed a disruption of cellular integrity and were indistinguishable from those exposed to penicillin. These studies demonstrate another class of microorganisms susceptible in vitro to vancomycin. PMID- 8517702 TI - Serum protein-binding characteristics of vancomycin. AB - A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein. Using an ultrafiltration method for separating free from bound drug and high performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin. The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM. Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins. We calculated an N (number of binding sites per molecule) of 1.3 +/ 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA. Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective. PMID- 8517703 TI - Comparative study of bioavailabilities and pharmacokinetics of clindamycin in healthy volunteers and patients with AIDS. AB - The absolute oral bioavailability and pharmacokinetics of clindamycin administered to 16 healthy volunteers and 16 patients with AIDS were compared. Clindamycin was given intravenously (i.v.) (Cleocin phosphate) at a dose of 600 mg as a 25-min infusion and orally (Cleocin hydrochloride) by use of a crossover design in both study groups. Plasma samples were analyzed by gas-liquid chromatography. Plasma drug clearance and volume of distribution at the steady state following the i.v. dose differed between study groups. The clearances were 0.27 +/- 0.06 liter/h/kg in healthy volunteers and 0.21 +/- 0.06 liter/h/kg in AIDS patients (P = 0.014; Mann-Whitney U test); the volumes of distribution at the steady state were 0.79 +/- 0.13 and 0.66 +/- 0.12 liter/kg in healthy volunteers and AIDS patients, respectively (P = 0.005). The elimination half-life did not differ between the two groups. The bioavailability of clindamycin capsules in AIDS patients was approximately 1.5 times that in healthy volunteers (0.53 +/- 0.14 versus 0.75 +/- 0.20; P = 0.002). Peak concentrations following the oral dose were higher in AIDS patients as well (7.7 +/- 2.5 versus 5.3 +/- 1.0 mg/liter; P = 0.0008). Three AIDS patients experienced severe diarrhea following the oral dose; four patients had mild diarrhea following the i.v. dose. No adverse effects were reported by the healthy volunteers. The pharmacokinetic parameters observed in this study for AIDS patients may be useful for the consideration of clindamycin dosage regimens in patients treated for toxoplasmic encephalitis. These findings suggest that the effect of AIDS on drug disposition deserves further investigation, particularly for orally administered drugs. PMID- 8517704 TI - blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin resistant Staphylococcus aureus. AB - For Staphylococcus aureus, it is hypothesized that two genes located upstream of the beta-lactamase gene, blaZ, are required for the inducible expression of beta lactamase. blaR1 is predicted to encode a signal-transducing membrane protein, and blaI is predicted to encode a repressor protein. These same two genes may also regulate the production of penicillin-binding protein 2a (PBP 2a), a protein essential for expression of methicillin resistance. To confirm that these two genes encode products that can control both beta-lactamase and PBP 2a production, blaI, blaR1, and blaZ with a 150-nucleotide deletion at the 3' end were subcloned from a 30-kb staphylococcal beta-lactamase plasmid and three beta-lactamase negative strains of methicillin-resistant S. aureus were transformed with the recombinant plasmid containing that insert. The production of PBP 2a and a nonfunctional beta-lactamase was detected by fluorography and by immunoblots with polyclonal antisera directed against each of the proteins. Whereas the parent strains did not produce beta-lactamase and constitutively produced PBP 2a, PBP 2a and a truncated beta-lactamase were now inducible in the transformants. Therefore, two plasmid-derived genes regulate the production of both PBP 2a and beta-lactamase. PMID- 8517705 TI - In vitro postantibiotic effects following multiple exposures of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli in pooled human cerebrospinal fluid and Mueller-Hinton broth. AB - Multiple exposures with cefotaxime in either Mueller-Hinton broth or cerebrospinal fluid had no effect on killing or the duration of postantibiotic effect (PAE) in Escherichia coli strains tested. However, upon multiple exposures in Mueller-Hinton broth, ciprofloxacin and gentamicin PAEs significantly decreased with a concomitant reduction in bacterial killing. A reduction in bacterial killing following multiple ciprofloxacin and gentamicin exposures was also seen with cerebrospinal fluid; however, the PAE was maintained. PMID- 8517706 TI - In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents. AB - The susceptibility of Streptococcus mutans to chlorhexidine and to six commonly used, systemic antibacterial agents (amoxicillin, cefuroxime, penicillin, sulfamethoxazole-trimethoprim, tetracycline, and erythromycin) was studied for 424 clinical isolates from 116 children and students. The MIC of chlorhexidine for all isolates was < or = 1 micrograms/ml. No resistance to the other antimicrobial agents was detected. Although widely exposed to various antimicrobial agents, S. mutans has remained susceptible to common antimicrobial agents, most importantly to chlorhexidine. PMID- 8517707 TI - Derivation and characterization of a quinapyramine-resistant clone of Trypanosoma congolense. AB - Over a period of 208 days a quinapyramine-resistant population was derived in vivo from a quinapyramine-susceptible clone of Trypanosoma congolense: IL 1180. While the dose of quinapyramine sulfate required to cure 50% of mice infected with the parental clone was 0.23 mg/kg of body weight, the 50% curative dose for the resistant derivative, IL 1180/Stabilate 12, was greater than 9.6 mg/kg. This approximately 40-fold increase in resistance to quinapyramine was shown to be associated with an 8-fold increase in resistance to isometamidium, a 28-fold increase in resistance to homidium, and a 5.5-fold increase in resistance to diminazene. Cross-resistance to homidium and diminazene was also demonstrated in goats. Two clones derived from the drug-resistant derivative underwent cyclical development in Glossina morsitans centralis, producing mature infection rates of 39.6 and 23.9%. Thus, induction of resistance to quinapyramine in T. congolense IL 1180 was associated with cross-resistance to isometamidium, homidium, and diminazene and did not compromise the population's ability to undergo full cyclical development in tsetse flies. PMID- 8517708 TI - Use of an in vivo system to determine the G418 resistance phenotype of bloodstream-form Trypanosoma brucei brucei transfectants. AB - We determined the level of susceptibility of Trypanosoma brucei brucei to the aminoglycoside G418 in vivo and demonstrated that it is possible to select for G418-resistant transfected T. brucei brucei bloodstream parasites in a mouse host by inoculating the drug intraperitoneally at doses between 40 and 80 mg/kg of body weight daily for 3 days. The ability to select for transfectants in vivo offers new possibilities for studies on genetic recombination in these parasites. PMID- 8517709 TI - Influence of therapeutic plasmapheresis on elimination of ceftiaxone. AB - To study the plasma elimination rate of ceftriaxone given to patients undergoing plasmapheresis, a single 2-g intravenous dose of ceftriaxone was given to 11 patients who underwent plasmapheresis 3 h (early group) or 15 h (late group) later. Even though the early patient group had twofold more ceftriaxone removed than the late group, all individual patients had 24-h ceftriaxone levels of 9 micrograms/ml or higher. We conclude that patients undergoing plasmapheresis lasting 150 min or less may safely be treated with 2 g of ceftriaxone once daily without risking periods of subtherapeutic plasma ceftriaxone levels. PMID- 8517710 TI - Activities of the triazole D0870 in vitro and against murine blastomycosis. AB - The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml). In vivo, D0870 was approximately 100-fold more active than fluconazole on the basis of milligrams per kilogram of body weight given once daily (QD) against blastomycosis. D0870 doses of both 1 or 10 mg/kg given QD and 10 or 100 mg/kg given every other day prolonged survival (P < 0.001) over fluconazole (100 mg/kg given QD). A D0870 dosage of 1 mg/kg QD was equivalent to fluconazole given at 100 mg/kg in reduction of lung burdens of B. dermatitidis, and D0870 administered at 10 mg/kg QD and 10 or 100 mg/kg every other day caused greater reduction (P < 0.001). However, D0870 at 100 mg/kg given QD was lethally toxic, whereas fluconazole at 100 mg/kg was not. These results indicate that D0870 is an effective therapy for murine blastomycosis and should be further tested. PMID- 8517711 TI - Penetration of cefprozil into tonsillar and adenoidal tissues. AB - Penetration of cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of cefprozil by high performance liquid chromatographic assays. The concentrations of the cis isomer of cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis. PMID- 8517712 TI - In vitro susceptibility of Helicobacter pylori to several antimicrobial combinations. AB - Synergy between metronidazole and its hydroxymetabolite and between each compound and amoxicillin or tetracycline-HCl was determined against Helicobacter pylori. Metronidazole plus its hydroxymetabolite and either compound combined with amoxicillin showed synergism against all 10 strains of H. pylori tested. Metronidazole plus tetracycline-HCl or the hydroxymetabolite plus tetracycline HCl acted synergistically against seven and six strains, respectively, acted additively against three strains, and had no additional effect against one strain. These results may help to explain the in vivo efficacies of metronidazole combinations in the treatment of H. pylori-associated gastritis. PMID- 8517713 TI - Mobilization of the penicillinase gene in Enterococcus faecalis. AB - Enterococcus faecalis SF4855 is a beta-lactamase-producing isolate resistant to high levels of gentamicin, with determinants for these resistances on the chromosome. SF4855 transferred both determinants into E. faecalis FA2-2 and UV202 at a frequency of 10(-9) in the presence of the MLS plasmid pYN120. beta Lactamase and gentamicin resistance probes hybridized to three locations on the chromosome of FA2-2 transconjugants on contour-clamped homogeneous electric field electrophoresis. The study results suggest mobilization of the beta-lactamase determinant. PMID- 8517714 TI - Antimicrobial susceptibilities of enterococci isolated from hospitalized patients. AB - One hundred and one isolates of Enterococcus species isolated recently from hospitalized patients were evaluated in vitro for antibiotic susceptibility. Teicoplanin and mideplanin were the most active agents, followed by ramoplanin, vancomycin, ciprofloxacin, ampicillin, and imipenem. High-level resistance to gentamicin (MIC > 500 micrograms/ml) and/or streptomycin (MIC > 2,000 micrograms/ml) was found in 60 isolates. High-level resistance to ampicillin (MIC > or = 16 micrograms/ml) was found in 17 isolates. MBC studies revealed that ramoplanin possesses significant bactericidal activity. PMID- 8517715 TI - Effects of probenecid on the pharmacokinetics of allopurinol riboside. AB - Allopurinol riboside is an experimental agent for the treatment of leishmaniasis and American trypanosomiasis. Previous studies showed that after oral administration, unexpectedly low levels of allopurinol riboside in plasma are attributable to incomplete absorption and rapid renal clearance. In this randomized, crossover evaluation in healthy volunteers, probenecid reduces the renal clearance of allopurinol riboside, extends the half-life of allopurinol riboside in plasma, and triples the levels of allopurinol riboside in plasma. PMID- 8517716 TI - Ciprofloxacin for treatment of severe typhoid fever in children. AB - Eighteen children with bacteriologically confirmed severe typhoid fever were initially treated intravenously with ciprofloxacin (10 mg/kg of body weight per day). Clinical cure with eradication of multiresistant Salmonella typhi infection was observed in 17 patients (94.4%; 95% confidence interval [CI], 84 to 100%). Children regained normal consciousness within an average of 2 days (95% CI, 1.8 to 2.2 days). The temperatures of the children returned to normal within 3.3 days (95% CI, 3.1 to 3.5 days). Complications were not observed during the hospital stay or a 3-month follow-up period. Relapse and carrier state were also not encountered during the follow-up period. PMID- 8517717 TI - Antimicrobial resistance of Salmonella isolates in a Spanish hospital. AB - We studied 961 clinical Salmonella isolates (one per patient) seen in one Spanish hospital from 1988 to 1991. The incidence of non-Salmonella typhi Salmonella infections per 100,000 admissions increased from 3.93 to 5.98. Overall rates of resistance to ampicillin, chloramphenicol, and co-trimoxazole were 32, 11, and 2%, respectively. Resistance to chloramphenicol increased from 9 to 16% during the study period, while resistance to each of the other drugs remained stable. Variations related to serogroups were observed. PMID- 8517718 TI - Antimicrobial susceptibility of Capnocytophaga spp. PMID- 8517719 TI - Prevention of hospital-acquired pneumonia in critically ill patients. PMID- 8517720 TI - Biochemical properties of a carbapenem-hydrolyzing beta-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. AB - A clinical isolate of Enterobacter cloacae, strain NOR-1, exhibited resistance to imipenem and remained susceptible to extended-spectrum cephalosporins. Clavulanic acid partially restored the susceptibility of the strain to imipenem. Two beta lactamases with isoelectric points (pI) of 6.9 and > 9.2 were detected in strain E. cloacae NOR-1; the higher pI corresponded to AmpC cephalosporinase. Plasmid DNA was not detected in E. cloacae NOR-1 and imipenem resistance could not be transferred into Escherichia coli JM109. The carbapenem-hydrolyzing beta lactamase gene was cloned into plasmid pACYC184. One recombinant plasmid, pPTN1, harbored a 5.3-kb Sau3A fragment from E. cloacae NOR-1 expressing the carbapenem hydrolyzing beta-lactamase. This enzyme (pI 6.9) hydrolyzed ampicillin, cephalothin, and imipenem more rapidly than it did meropenem and aztreonam, but it hydrolyzed extended-spectrum cephalosporins only weakly and did not hydrolyze cefoxitin. Hydrolytic activity was partially inhibited by clavulanic acid, sulbactam, and tazobactam, was nonsusceptible to chelating agents such as EDTA and 1,10-o-phenanthroline, and was independent of the presence of ZnCl2. Its relative molecular mass was 30,000 Da. Induction experiments concluded that the carbapenem-hydrolyzing beta-lactamase biosynthesis was inducible by cefoxitin and imipenem. Subcloning experiments with HindIII partial digests of pPTN1 resulted in a recombinant plasmid, designated pPTN2, which contained a 1.3-kb insert from pPTN1 and which conferred resistance to beta-lactam antibiotics. Hybridization studies performed with a 1.2-kb HindIII fragment from pPtN2 failed to determine any homology with ampC of E. cloacae, with other known beta-lactamase genes commonly found in members of the family Enterobacteriaceae (bla(TEM-1)) and bla(SHV-3) derivatives), and with previously described carbapenemase genes such as those from Xanthomonas maltophilia, Bacillus cereus, Bacteroides fragilis (cfiA), and Aeromonas hydrophila (cphA). This work describing the biochemical properties of a novel chromosome-encoded beta-lactamase from E. cloacae indicates that this enzyme differs from all the previously described carbapenemases. This is the first reported cloning of a carbapenem-hydrolyzing gene from a member of the family Enterobacteriaceae. PMID- 8517721 TI - In vitro activity of FK037, a new parenteral cephalosporin, against anaerobic bacteria. AB - The activity of FK037, a new parenteral cephalosporin, was compared with those of cefpirome, ceftazidime, and flomoxef against 322 recent clinical isolates of anaerobic bacteria. A fastidious facultative anaerobe, Gardnerella vaginalis, was also studied. FK037 inhibited 90% of isolates of Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Clostridium perfringens, Mobiluncus spp., G. vaginalis, and Porphyromonas gingivalis at < or = 0.78 micrograms/ml. The MICs of FK037 for 50 and 90% of Bacteroides fragilis isolates were 25 and > 200 micrograms/ml, respectively; the activity of FK037 was comparable to those of cefpirome and ceftazidime but lower than that of flomoxef. The activity of FK037 against Fusobacterium nucleatum, Fusobacterium varium, and Bilophila wadsworthia decreased when inoculum size was increased from 10(6) to 10(8) CFU/ml. Little influence of inoculum size on the activity of FK037 was observed for other isolates tested. Medium pH affected the activity of FK037 against F. varium (MICs at pHs 5 and 7, 3.13 and 100 micrograms/ml, respectively) and Bacteroides gracilis (MICs at pHs 5 and 7, 12.5 and 1.56 micrograms/ml, respectively) but not against other organisms tested. FK037 was less resistant than flomoxef to hydrolysis by beta-lactamase group 2e derived from B. fragilis GAI 0558 and GAI 10150. PMID- 8517722 TI - Characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa. AB - A clinical isolate of Pseudomonas aeruginosa RNL-1 showed resistance to extended spectrum cephalosporins which was inhibited by clavulanic acid. Although this strain contained three plasmids ca. 80, 20, and 4 kb long, the resistance could not be transferred by mating-out assays with P. aeruginosa or Escherichia coli. Cloning of a 2.1-kb Sau3A fragment from P. aeruginosa RNL-1 into plasmid pACYC184 produced pPZ1, a recombinant plasmid that encodes a beta-lactamase. This beta lactamase (PER-1) had a relative molecular mass of 29 kDa and a pI of 5.4 and was biosynthesized by P. aeruginosa RNL-1 along with a likely cephalosporinase with a pI of 8.7. PER-1 showed a broad substrate profile by hydrolyzing benzylpenicillin, amoxicillin, ticarcillin cephalothin, cefoperazone, cefuroxime, HR 221, ceftriaxone, ceftazidime, and (moderately) aztreonam but not oxacillin, imipenem, or cephamycins. Vmax values for extended-spectrum cephalosporins were uncommonly high, and the affinity of the enzyme for most compounds was relatively low (i.e., high Km). PER-1 activity was inhibited by clavulanic acid, sulbactam, imipenem, and cephamycins but not by EDTA. A 1.1-kb SnaBI fragment from pPZ1 failed to hybridize with plasmids that encode TEM-, SHV-, OXA-, or CARB/PSE-type beta-lactamase or with the ampC gene of P. aeruginosa. However, the same probe appeared to hybridize with chromosomal but not plasmid DNA from P. aeruginosa RNL 1. This study reports the properties of a novel extended-spectrum beta-lactamase in P. aeruginosa which may not be derived by point mutations from previously known enzymes of this species. PMID- 8517723 TI - Efficacy of intramuscular amopyroquin for treatment of Plasmodium falciparum malaria in the Gabon Republic. AB - The efficacy of a 12-mg/kg (of body weight) intramuscular amopyroquin (ApQ) regimen (two successive 6-mg/kg injections at a 24-h interval), previously established from kinetic studies on healthy volunteers and multicenter studies on patients with malaria, was investigated in 152 patients (children and adults) in Gabon with Plasmodium falciparum malaria. All children in the present study (ages, 1 to 14 years) showed higher degrees of parasitemia and temperatures and lower hematocrit values than did adults at the time of admission. No major side effects in the patients were observed. On day 7, all patients were apyretic; clearance of parasites was obtained in 143 of 152 patients (94%); a low level of parasitemia was observed in nine patients, all of whom were children (6%). In vitro chemosusceptibility tests carried out on P. falciparum isolates from patients demonstrated 51% of resistance to chloroquine (Cq). A correlation was found between the in vitro chemosusceptibilities to Cq and ApQ, but no relationship between the in vitro activity and the in vivo efficacy of ApQ could be found. Concentrations of ApQ in blood assayed by high-performance liquid chromatography on day 2 did not differ significantly between the groups in whom therapy was a success or a failure, although the mean ApQ concentration in blood for the group that failed therapy was 31% lower. Concentrations greater than 100 nmol of self-prescribed Cq and amodiaquine per liter, which were assayed simultaneously with ApQ, were observed in 78 patients (51%). They did not correlate with degrees of parasitemia compared with ApQ alone, which did. Successful treatment by day 7 was obtained in 69 of 74 patients (93%) who had no other 4-aminoquinolines in their blood. The results of the present study show that an ApQ regimen of 12 mg/kg over 2 days may be an alternative for the treatment of Cq-resistant malaria, at least in adult patients, in the field. PMID- 8517724 TI - Selective inhibition of the bacterial translocase reaction in peptidoglycan synthesis by mureidomycins. AB - Mureidomycins (MRDs) A and C inhibited strongly the formation of undecaprenyl pyrophosphoryl N-acetylmuramyl-pentapeptide (lipid intermediate I), which is an intermediate in bacterial peptidoglycan synthesis (50% inhibitory concentration [IC50] of MRD A, 0.05 microgram/ml). However, they did not inhibit the formation of dolichyl pyrophosphoryl N-acetylglucosamine (Dol-p-p-GlcNAc), dolichyl phosphoryl glucose, or dolichyl phosphoryl mannose, the precursors for mammalian glycoprotein synthesis, or the formation in Bacillus subtilis of lipid-linked N acetylglucosamine for teichoic acid synthesis (IC50s, > 100 micrograms/ml). In contrast, tunicamycin (TCM) inhibited strongly the formation of Dol-p-p-GlcNAc (IC50, 0.03 microgram/ml) but inhibited weakly the formation of bacterial lipid intermediate I (IC50, 44 micrograms/ml). When the effects of MRDs A and C and TCM on the growth of mammalian cells were compared, MRDs did not show any toxicity, even at 1,000 micrograms/ml, whereas TCM inhibited the growth of BALB/3T3 cells at 10 micrograms/ml. On the basis of these results, it was concluded that MRDs are the first specific and potent inhibitors of the translocase reaction in bacterial peptidoglycan synthesis, showing a high level of toxicity against bacteria and a low level of toxicity against mammalian cells. A specific inhibitor of translocase could be a potent antibiotic with highly selective toxicity. PMID- 8517725 TI - Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam. AB - Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. PMID- 8517726 TI - 9-Anilinoacridines as potential antileishmanial agents. AB - A number of 1'-substituted 9-anilinoacridines were evaluated for their activities against promastigote and amastigote forms of Leishmania major and for their toxicities to human Jurkat leukemia cells. Several compounds possessing 1'-NH alkyl substituents produced more than 80% growth inhibition of macrophage infected L. major amastigotes at or below a concentration of 1 microM. 1' Hexylamino-9-anilinoacridine (compound 14) was the least toxic compound to human Jurkat cells, while it retained strong antileishmanial activity. There was a general trend for the more lipophilic compounds to show the greatest antileishmanial activity, whereas 3,6-di-NH2 substitution of the acridine nucleus reduced or eliminated activity. Some structure-activity relationships of the various compounds are discussed. PMID- 8517727 TI - In vivo efficacies of quinolones and clindamycin for treatment of infections with Bacteroides fragilis and/or Escherichia coli in mice: correlation with in vitro susceptibilities. AB - Therapy with ofloxacin, ciprofloxacin, and lomefloxacin (alone or in combination with clindamycin) and therapy with sparfloxacin, clinafloxacin, and temafloxacin alone were given to mice with subcutaneous abscesses. The abscesses were caused by two Bacteroides fragilis isolates, one of which was susceptible and one of which was resistant to ofloxacin, ciprofloxacin, and lomefloxacin, alone or in combination with Escherichia coli. The abscesses were examined 5 days after inoculation. Numbers of B. fragilis organisms reached log10 10.2 to 11.8 per abscess, and numbers of E. coli organisms reached log10 10.6 to 11.8 per abscess. All of the quinolones reduced the number of susceptible B. fragilis isolates (log10 3.6 to 6.9) and E. coli isolates (log10 5.7 to 6.8). However, ciprofloxacin and lomefloxacin failed to reduce the number of resistant B. fragilis organisms in single-organism or mixed infections. The addition of clindamycin to either ofloxacin, ciprofloxacin, or lomefloxacin reduced the numbers of both susceptible and resistant B. fragilis organisms (log10 3.8 to 7.8). In contrast, sparfloxacin, clinafloxacin, and temafloxacin were effective as single therapy in eradicating B. fragilis resistant to ofloxacin, ciprofloxacin, and lomefloxacin. These in vivo data confirm the in vitro activity of these quinolones and suggest that although ofloxacin, ciprofloxacin, and lomefloxacin are occasionally effective as single agents in eradicating mixed infection by susceptible strains of B. fragilis and E. coli, addition of an agent with activity against anaerobic organisms will ensure their efficacy. Quinolones with good efficacy against B. fragilis may be effective as single-agent therapy of mixed infections. PMID- 8517728 TI - Production of polyclonal antibodies to the trichothecene mycotoxin 4,15 diacetylnivalenol with the carrier-adjuvant cholera toxin. AB - The trichothecene mycotoxin 4,15-diacetylnivalenol (DNIV) was conjugated to cholera toxin (DNIV-CT) for use as an immunogen and as an adjuvant for specific antibody production. Repeated intravenous injection of 7.5 micrograms of the conjugate was effective at generating specific antibodies to DNIV in rabbits as determined by enzyme-linked immunosorbent assay (ELISA). When small amounts (1 to 10 micrograms per animal) of DNIV-CT were used to immunize mice, polyclonal antibodies were observed as early as 4 weeks of immunization. The relative affinity of the antibodies to DNIV increased with the immunogen dose in mice. Antibodies were not detectable in either rabbits or mice that were injected with DNIV conjugated to the carrier protein bovine serum albumin or when DNIV-CT was blocked with glutaraldehyde. Competitive ELISA of mouse and rabbit serum revealed that the antibodies were most specific for DNIV but reacted to a small extent with fusarenone-X, deoxynivalenol, and nivalenol. No reactivity was observed with 3- or 15-acetyldeoxynivalenol. The results suggest that specific polyclonal antibodies can be prepared against a trichothecene when CT is used as an adjuvant and carrier protein. DNIV antibodies will be useful for monitoring the compound in food in conjunction with other trichothecene antibodies, detection of DNIV producing cultures, and investigation of 8-ketotrichothecene biosynthesis. PMID- 8517729 TI - Role of Campylobacter jejuni flagella as colonization factors for three-day-old chicks: analysis with flagellar mutants. AB - Campylobacter jejuni, an important cause of human gastrointestinal infection, is a major food-borne pathogen in the United States and worldwide. Since poultry becomes colonized and/or contaminated during the early stages of production and is a major food-borne source for this organism, we studied the role of C. jejuni flagella on the ability of the bacterium to colonize the chicken gastrointestinal tract. Three-day-old chicks were orally challenged with a motile wild-type strain of C. jejuni IN9 or with flagellar mutants created from IN9 by disrupting the flagellin genes with a kanamycin resistance cassette by using shuttle mutagenesis (A. Labigne-Roussel, P. Courcoux, and L. Tompkins, J. Bacteriol. 170:1704-1708, 1988). One mutant, IN9-N3, lacked flagella and was nonmotile. The other, IN9-N7, produced a truncated flagellum and was partially motile. Three-day-old chicks were orally challenged with different doses of the wild-type strain and the two mutants. At challenge doses ranging from 3.0 x 10(4) to 6.6 x 10(8) CFU per chick, only the fully motile, wild-type strain colonized the chick ceca. Our results show that intact and motile flagella are important colonization factors for C. jejuni in chicks. PMID- 8517730 TI - Detection of Listeria monocytogenes in cheese with the magnetic immuno-polymerase chain reaction assay. AB - A new detection system, the magnetic immuno-polymerase chain reaction (PCR) assay (MIPA) has been developed to detect Listeria monocytogenes in food. This method separates Listeria cells from PCR-inhibitory factors present in enrichment broths containing food samples by using magnetic beads coated with specific monoclonal antibodies (MAbs). The separated bacteria were lysed, and the supernatant containing the bacterial DNA was subjected to the PCR. Detection of L. monocytogenes in three naturally contaminated cheese samples with two different MAbs and PCR primers specific for the gene encoding the delayed-hypersensitivity factor showed that with MAb 55 all three samples were positive whereas with MAb A two samples were positive. A further improvement of the method was obtained by using a PCR step based on the listeriolysin O gene. A MIPA employing MAb 55 and the listeriolysin O gene primer set detected L. monocytogenes after 24 h of culture in Listeria Enrichment Broth samples from Port Salut artificially contaminated with 40 CFU/25 g. We could detect 1 CFU of L. monocytogenes per g of cheese after a second enrichment for 24 h in Fraser broth. The analysis time including both enrichments is approximately 55 h. PMID- 8517731 TI - Rapid detection of salmonellae in poultry with the magnetic immuno-polymerase chain reaction assay. AB - Rapid detection of salmonellae in chicken meat was accomplished by using the magnetic immuno-polymerase chain reaction assay (MIPA). A direct polymerase chain reaction assay performed with chicken meat spiked with Salmonella typhimurium resulted in poor sensitivity (approximately 10(7) CFU/g of meat). The use of immunoseparation with a Salmonella serogroup B-specific monoclonal antibody improved the sensitivity, but enrichment was required for the detection of low levels of contamination. Enrichment for 6 h in either buffered peptone water, lactose broth containing tergitol-7, or selenite-cystine broth resulted in the detection of an initial inoculum of 100 CFU per g of meat. Enrichment of the salmonellae present on 25 g of spiked chicken meat for 24 h in either buffered peptone water or selenite-cystine broth before detection by the MIPA yielded a detection limit of approximately 0.1 CFU/g of meat. A detection limit of approximately 1 CFU/g of meat was obtained when the spiked meat was stored at -20 degrees C before enrichment for 24 h and analysis with the MIPA. Although the MIPA was developed for S. typhimurium, a MIPA in which a panel of six monoclonal antibodies specific for Salmonella serogroups A through E was used detected the presence of 0.1 CFU of Salmonella enteritidis per g of chicken meat. These data indicate that the method is applicable to other commonly isolated serotypes. PMID- 8517732 TI - Conditional suicide system of Escherichia coli released into soil that uses the Bacillus subtilis sacB gene. AB - The sacB gene from Bacillus subtilis confers sucrose sensitivity upon gram negative bacteria. The gene was investigated for use as a potential conditional suicide system for Escherichia coli released into soil. To ensure against the loss of the cell death function encoded under nonselective conditions, the nptI sacR-B suicide cassette was inserted into the E. coli chromosome by using a circular nonreplicative integration vector. Stability studies yielded no loss of the suicide cassette in the integrated E. coli EL1026 strain. sacB induction in the absence of a selective pressure resulted in a lysis efficiency of up to 99.9%. The microcosm experiments confirmed the ability of the suicide cassette to limit the growth and reduce the survival of E. coli strains released into soil. Sucrose addition to sterile soil resulted in a 10(-3)-fold reduction of the final E. coli population density. sacB induction prevented the proliferation and triggered the rapid disappearance of E. coli from natural soil. Mutation to sucrose tolerance occurred at a frequency of 10(-5), making E. coli EL1026 a potential counterselectable donor strain for gene transfer studies. Specificity and potential adaptability to a wide range of gram-negative bacteria are additional conveniences of this conditional suicide system for the containment and counterselection of engineered microorganisms. PMID- 8517733 TI - Further studies on the feasibility of one-day Salmonella detection by enzyme linked immunosorbent assay. AB - A model system previously developed for the rapid detection of Salmonella typhimurium in foods was improved and extended to many other Salmonella serotypes. The original protocol, which consisted of an overnight nonselective culture followed by a specific enzyme-linked immunosorbent assay (ELISA), was modified and improved. A sandwich ELISA which used polyclonal antibodies for the capture stage and a cocktail of monoclonal antibodies for the detector stage was developed. The assay recognized a wide range of Salmonella serotypes; S. enteritidis, the most important serotype in the United Kingdom had a detection limit in the ELISA of about 4 x 10(2) cells ml-1. The cultural stage prior to the ELISA was either a single nonselective broth (incubated for 28 h) or a preenrichment broth (incubated for 7 h) plus a selective broth (incubated for 21 h). Antibodies which bind to cells grown in the unfavorable conditions of a selective medium were selected. It was concluded that, in the future, the shortened protocols for the detection of Salmonella spp. in foods described here will be of considerable value. PMID- 8517734 TI - Identification of procaryotic repetitive DNA suitable for use as fingerprinting probes. AB - We have developed a method which enables the cloning and identification of procaryotic repetitive DNA suitable for use as DNA fingerprinting probes. The method involves shotgun cloning of restricted genomic DNA with subsequent selection of clones containing repetitive DNA by reverse-probed genomic hybridizations, in which the plasmid DNA clones are probed with labelled genomic DNA. Confirmation that the clones contained repeated sequences was by Southern hybridization, gene copy equivalence, and DNA sequencing. The sequences were used for highly specific and sensitive detection of bacteria and as target sequences for the mediation of chromosomal integration of reporter gene constructs. PMID- 8517735 TI - Purification and characterization of the extracellular alpha-amylase from Streptococcus bovis JB1. AB - The extracellular alpha-amylase (1,4-alpha-D-glucanglucanohydrolase; EC 3.2.1.1) from maltose-grown Streptococcus bovis JB1 was purified to apparent homogeneity by ion-exchange chromatography (Mono Q). The enzyme had an isoelectric point of 4.50 and an apparent molecular mass of 77,000 Da, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was rich in acidic and hydrophobic amino acids. The 15-amino-acid NH2-terminal sequence was 40% homologous with the Bacillus subtilis saccharifying alpha-amylase and 27% homologous with the Clostridium acetobutylicum alpha-amylase. alpha-Amylase activity on soluble starch was optimal at pH 5.0 to 6.0. The enzyme was relatively stable between pH 5.5 and 8.5 and at temperatures below 50 degrees C. When soluble potato starch was used as the substrate, the enzyme had a Km of 0.88 mg.ml-1 and a kcat of 2,510 mumol of reducing sugar.min-1.mg of protein-1. The enzyme exhibited neither pullulanase nor dextranase activity and was 40 to 70% as active on amylopectin as on amylose. The major end products of amylose hydrolysis were maltose, maltotriose, and maltotetraose. PMID- 8517736 TI - Bromoalkane-degrading Pseudomonas strains. AB - Two Pseudomonas isolates, named ES-1 and ES-2, were shown to possess a wide degradative spectrum for haloalkanes in general and bromoalkanes in particular but did not degrade nonsubstituted alkanes. The utilization of water-insoluble haloalkanes, such as 1-bromooctane, appeared to consist of three phases: (i) extracellular emulsification by a constitutively excreted, broad-spectrum surface active agent, (ii) dehalogenation by an inducible hydrolytic dehalogenase (possibly periplasmic), and (iii) intracellular degradation of the residual carbon skeleton. Several observations suggest the existence of more than one dehalogenase in strain ES-2. PMID- 8517737 TI - Distribution of bacteria within operating laboratory water purification systems. AB - Experiments were conducted to measure communities of bacteria within operating ultrapure water treatment systems intended for laboratory use. Samples from various locations within Milli-Q Plus and Milli-Q UV Plus systems were analyzed for populations of planktonic bacteria at weekly intervals over 3 months of operation. Relatively high initial densities of planktonic bacteria (10(2) to 10(3) bacteria per ml) were seen within both units when they were challenged with source water of poor quality, although the product water continued to be acceptable with regard to bacterial numbers, resistivity, and endotoxin concentration. Under more normal operating conditions, significant differences were seen in planktonic populations throughout the systems with excellent product water quality. A great deal of variability was observed in biofilm populations analyzed from various system surfaces after 3 months of operation. The concentrations of planktonic bacteria and biofilm densities were much lower in the unit containing a UV lamp. These findings suggest that a range of microenvironmental conditions exist within purified water systems, leading to variable populations of bacteria. However, product water of excellent quality was obtained despite the bacterial communities. PMID- 8517738 TI - Growth and cholesterol oxidation by Mycobacterium species in Tween 80 medium. AB - Mycobacterium strain DP was isolated from marine coastal sediment and tested for its ability to oxidize cholesterol in Tween 80-cholesterol (2.59 mM) medium. Strain DP degraded cholesterol to 4-cholesten-3-one (cholestenone), 4-androsten 3,17-dione (AD), 1,4-androstadien-3,17-dione (ADD), testosterone, and 1 dehydrotestosterone (DHT). Cholesterol disappeared in about 4 days. Cholestenone, AD, testosterone, and DHT accumulations were transient with peak concentrations of 300, 600, 30 to 40, and 21 microM. ADD production peaked after 6 days with a concentration of 1,100 microM. Peak ADD concentrations and production rates compared well with those reported for strain NRRL B3683 on cyclodextrin medium. Tween 80 medium was superior to finely dispersed cholesterol particles for both strains. In comparison, NRRL B3683 (patented for its ability to accumulate AD and ADD) on Tween 80 medium transiently accumulated more AD (approximately 1,000 microM) than did strain DP, but ADD accumulations (200 microM) were significantly lower than those for strain DP. Strain DP could be adapted to grow on ADD, which was initially inhibitory at 3.25 mM. ADD-adapted strain DP cultures produced approximately four times as much DHT from ADD than unadapted cultures did from cholesterol, showing that additional manipulation might enhance testosterone production. We believe that ADD toxicity might account for the low ADD accumulations by NRRL B3683 in Tween 80 medium. PMID- 8517739 TI - Evidence for the existence of independent chloromethane- and S-adenosylmethionine utilizing systems for methylation in Phanerochaete chrysosporium. AB - O methylation of acetovanillone at 4 position by C2H3Cl and S-adenosyl[methyl 2H3]methionine was monitored in whole mycelia of Phanerochaete chrysosporium in the presence and absence of S-adenosylhomocysteine. Both the amount of the methylation product, 3,4-dimethoxyacetophenone, and the percent C2H3 incorporation into the 4-methoxyl group of the compound were determined. The results strongly suggest the presence of biochemically distinct systems for O methylation of acetovanillone utilizing S-adenosylmethionine and chloromethane, respectively, as the methyl donor. The S-adenosylmethionine-dependent enzyme is induced early in the growth cycle, with activity attaining an initial maximum after 55 h of incubation. Methylation by this enzyme is totally suppressed by 1 mM S-adenosylhomocysteine over almost the entire growth cycle. S Adenosylmethionine-dependent O-methyltransferase activity is detectable in cell extracts, and the purification and characterization of the enzyme are described elsewhere (C. Coulter, J. T. Kennedy, W. C. McRoberts, and D. B. Harper, Appl. Environ. Microbiol. 59:706-711, 1993). The chloromethane-utilizing methylation system is absent in early growth but attains peak activity in the mid-growth phase after 72 h of incubation. The system is not significantly inhibited by S adenosylhomocysteine at any stage of growth. No chloromethane-dependent O methyltransferase activity is detectable in cell extract, suggesting that the enzyme is membrane bound and/or part of a multienzyme complex. Although the biochemical role of the chloromethane-dependent methylation system in metabolism is not known, one possible function could be the regeneration of veratryl alcohol degraded by the attack of lignin peroxidase. PMID- 8517740 TI - Detection of tetracycline resistance determinants in pig isolates from three herds with different histories of antimicrobial agent exposure. AB - A total of 114 gram-negative fecal isolates from domestic pigs in herds with different histories of antimicrobial agent exposure were screened for the presence of plasmid DNA and specific tetracycline resistance determinants. More than 84% of the isolates harbored plasmid DNA, which ranged in size from 2.1 to 186 kb. A total of 78 isolates (68.4%) were resistant to tetracycline at concentrations greater than 4 micrograms/ml. Plasmid DNAs from about 56% of the tetracycline-resistant isolates hybridized with DNA probes for class A, B, C, and D tetracycline resistance determinants. The class B determinant was the most common determinant (35% of the isolates), followed by the class C determinant (12%) and the class A determinant (1%). About 9% of the isolates contained two determinants on plasmids. None of the plasmids from isolates hybridized with the class D determinant probe. The class C determinant was the most prevalent determinant on plasmids in isolates from pigs not exposed to antimicrobial agents for more than 146 months, while the class B determinant was more prevalent on plasmids in isolates from pigs exposed to either subtherapeutic or therapeutic levels of antimicrobial agents. Most tetracycline resistance determinants were localized on plasmids which were more than 30 kb long. A great number of wild type tetracycline-resistant Escherichia coli strains were found with the class E determinant on their chromosomes. This study revealed a high prevalence of tetracycline resistance determinants in the fecal flora of pig herds whether or not they were fed with antibiotics. PMID- 8517741 TI - Specific detection of Salmonella spp. by multiplex polymerase chain reaction. AB - Three sets of oligonucleotide primers were used in the polymerase chain reaction (PCR) assay to detect Salmonella species. phoP primers specific to the phoP/phoQ loci of coliform pathogenic bacteria such as Salmonella, Shigella, Escherichia coli, and Citrobacter species served as presumptive indicators of enteric bacteria. In addition to the phoP primers, the Hin and the H-1i primers, which targeted a 236-bp region of hin/H2 and a 173-bp region of the H-1i flagellin gene, respectively, were used. Both Hin and H-1i primers are specific to motile Salmonella species and are not present in Shigella, E. coli, or Citrobacter species. Thus, by multiplex PCR amplification, Salmonella species including Salmonella typhi, Salmonella typhimurium, Salmonella paratyphi A, and Salmonella enteritidis can be specifically detected. Optimal reaction conditions have been described to demonstrate this specific, sensitive detection of Salmonella species. By using agarose gel electrophoresis for detection of the PCR-amplified products, the sensitivity of detection was 10(2) CFU after 25 cycles of PCR and 1 (10(0)) CFU after a 50-cycle double PCR. The efficacy of these primers was demonstrated on environmental isolates which had previously been confirmed as Salmonella species by the use of conventional cultural techniques. In addition, positive amplifications resulted from Salmonella species in environmental samples including soil and water. PMID- 8517742 TI - Purification, characterization, and lytic activity against Naegleria fowleri of two amoebicins produced by Bacillus licheniformis A12. AB - Bacillus licheniformis A12 produces two amoebolytic substances (amoebicins A12-A and A12-B) in liquid media during sporulation. Both substances have been purified and characterized. They are heat- and protease-resistant peptides containing aspartic acid, glutamic acid, serine, proline, and tyrosine in a molar ratio of 5:2:2:2:2. No fatty acids or carbohydrates have been detected. Their molecular weight is 1,430. Purified amoebicins A12-A and A12-B exhibit amoebolytic action against Naegleria fowleri. They also exhibit antibiotic action against yeasts (Saccharomyces heterogenicus and Cryptococcus neoformans) and several fungal species (Aspergillus niger, Microsporum canis, Mucor plumbeus, and Trychophyton mentagrophytes). Their antibacterial spectrum appears to be restricted to Bacillus megaterium, Corynebacterium glutamicum, and Sarcina sp. PMID- 8517743 TI - Role of D-ribose as a cometabolite in D-xylose metabolism by Saccharomyces cerevisiae. AB - The influence of D-ribose as a cosubstrate on the uptake and metabolism of the non-growth substrate D-xylose by Saccharomyces cerevisiae ATCC 26602 was investigated. Xylose was taken up by means of low- and high-affinity glucose transport systems. In cells exposed for 2 days to a mixture of xylose and ribose, only the high-affinity system could be detected. Glucose strongly inhibited the transport of xylose by both systems. Starvation or exposure to either xylose or ribose resulted in inactivation of xylose transport, which did not occur in the presence of a mixture of ribose and xylose. A constitutive non-glucose repressible NADPH2-dependent xylose reductase with a specific activity of ca. 5 mU/mg of protein that converted xylose to xylitol was present in a glucose-grown culture. No activity converting xylitol to xylulose or vice versa was found in crude extracts. Both xylose and ribose were converted to their corresponding polyols, xylitol and ribitol, as indicated by 13C nuclear magnetic resonance spectroscopy. Furthermore, ethanol was detected, and this implied that pathways for the complete catabolism of xylose and ribose exist. However, the NADPH2 required for the conversion of xylose to xylitol is apparently not supplied by the pentose phosphate pathway since the ethanol produced from D-[1-13C]xylose was labelled only in the C-2 position. Acetic acid was produced from ribose and may assist in the conversion of xylose to xylitol by cycling NADPH2. PMID- 8517744 TI - Microbial oxidation of dimethylnaphthalene isomers. AB - Three bacterial strains, identified as Alcaligenes sp. strain D-59 and Pseudomonas sp. strains D-87 and D-186, capable of growing on 2,6 dimethylnaphthalene (2,6-DMN) as the sole source of carbon and energy were isolated from soil samples. 2,6-Naphthalene dicarboxylic acid was formed in the culture broths of these three strains grown on 2,6-DMN. In addition, 2 hydroxymethyl-6-methylnaphthalene and 6-methylnaphthalene-2-carboxylic acid were detected in the culture broth of strain D-87. Strain D-87 grew well on 1,2-, 1,3 , 1,4-, 1,5-, 2,3-, and 2,7-DMN as the sole source of carbon and energy and accumulated 2-methylnaphthalene-3-carboxylic acid and 2,3-naphthalene dicarboxylic acid from 2,3-DMN, 4-methylnaphthalene-1-carboxylic acid from 1,4 DMN, and 7-methylnaphthalene-2-carboxylic acid from 2,7-DMN. PMID- 8517745 TI - Effects of chemical speciation in growth media on the toxicity of mercury(II). AB - The toxicity of metals, including mercury, is expressed differently in different media, and the addition of soluble organics to the growth medium can have a significant impact on bioassay results. Although the effect of medium composition on metal toxicity is generally attributed to its effect on metal speciation (i.e., the chemical form in which the metal occurs), the importance of individual metal-ligand species remains largely unclear. Here, we report the results of a study that investigated, both experimentally and from a modeling perspective, the effects of complex soluble organic supplements on the acute toxicity (i.e., 50% inhibitory concentration [IC50]) of mercury to a Pseudomonas fluorescens isolate in chemically well-defined synthetic growth media (M-IIX). The media consisted of a basal inorganic salts medium supplemented with glycerol (0.1%, vol/vol) and a variety of common protein hydrolysates (0.1%, vol/vol), i.e., Difco beef extract (X = B), Casamino Acids (X = C), peptone (X = P), soytone (X = S), tryptone (X = T), and yeast extract (X = Y). These were analyzed to obtain cation, anion, and amino acid profiles and the results were used to compute the aqueous speciation of Hg(II) in the media. Respirometric bioassays were performed and IC50s were calculated. Medium components varied significantly in their effects on the acute toxicity of Hg(II) to the P. fluorescens isolate. IC50s ranged from 1.48 to 14.54 micrograms of Hg ml-1, and the acute toxicity of Hg(II) in the different media decreased in the order M-IIC >> M-IIP > M-IIB >> M-IIT > M-IIS >>> M IIY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517746 TI - Repair and enterotoxin synthesis by Staphylococcus aureus after thermal shock. AB - To study repair and enterotoxin synthesis, four staphylococcal strains (FRI-100, FRI-137, FRI-472, and S6) were subjected to sublethal heat treatment, transferred to four liquid repair media (1% powdered skim milk in distilled water, complex medium, M9 minimal salt medium, and saline solution), and then incubated at different temperatures. Powdered skim milk proved to be the most efficient medium for promoting the repair of injured cells, particularly at 37 degrees C. Minimal salt medium also gave good results. Salt tolerance also increased at 4 degrees C, although it did not reach normal values. After 6 h of incubation at 37 degrees C in powdered skim milk, strain FRI-100 synthesized detectable amounts of enterotoxin A. After 10 h of incubation in the same medium at the same temperature, enterotoxins were detected in all of the strains. PMID- 8517747 TI - Probing activated sludge with oligonucleotides specific for proteobacteria: inadequacy of culture-dependent methods for describing microbial community structure. AB - Bacterial community structures in activated sludge samples from aeration tanks of a two-stage system with a high-load first stage and a low-load second stage were analyzed with oligonucleotide probes. The probes were complementary to conserved regions of the rRNA of the alpha, beta, and gamma subclasses of proteobacteria and of all bacteria. Group-specific cell counts were determined by in situ hybridization with fluorescent probe derivatives. Contributions of the proteobacterial subclasses to total bacterial rRNA were quantified by dot blot hybridization with digoxigenin-labeled oligonucleotides. The activated sludge samples were dominated by proteobacteria from the alpha, beta, or gamma subclass. These proteobacteria account for about 80% of all active bacteria found in the activated sludge. For both samples the community structures determined with molecular techniques were compared with the composition of the heterotrophic saprophyte flora isolated on nutrient-rich medium. Probes were used to rapidly classify the isolates and to directly monitor population shifts in nutrient amended, activated sludge samples. The rich medium favored growth of gamma subclass proteobacteria (e.g., enterobacteria) and selected against beta-subclass proteobacteria. The culture-dependent community structure analysis of activated sludge produced partial and heavily biased results. A more realistic view will be obtained by using in situ techniques. PMID- 8517748 TI - Evaluation and simplification of the assimilable organic carbon nutrient bioassay for bacterial growth in drinking water. AB - A modified assimilable organic carbon (AOC) bioassay is proposed. We evaluated all aspects of the AOC bioassay technique, including inoculum, incubation water, bioassay vessel, and enumeration technique. Other concerns included eliminating the need to prepare organic carbon-free glassware and minimizing the risks of bacterial and organic carbon contamination. Borosilicate vials (40 ml) with Teflon-lined silicone septa are acceptable incubation vessels. Precleaned vials are commercially available, and the inoculum can be injected directly through the septa. Both bioassay organisms, Pseudomonas fluorescens P-17 and Spirillum sp. strain NOX, are available from the American Type Culture Collection and grow well on R2A agar, making this a convenient plating medium. Turbid raw waters need to be filtered prior to an AOC analysis. Glass fiber filters used with either a peristaltic pump or a syringe-type filter holder are recommended for this purpose. A sampling design that emphasizes replication of the highest experimental level, individual batch cultures, is the most efficacious way to reduce the total variance associated with the AOC bioassay. Quality control for the AOC bioassay includes an AOC blank and checks for organic carbon limitation and inhibition of the bioassay organisms. PMID- 8517749 TI - Relationships among non-Acremonium sp. fungal endophytes in five grass species. AB - Many cool-season grasses (subfamily Pooideae) possess maternally transmitted fungal symbionts which cause no known pathology and often enhance the ecological fitness and biochemical capabilities of the grass hosts. The most commonly described endophytes are the Acremonium section Albo-lanosa spp. (Acremonium endophytes), which are conidial anamorphs (strictly asexual forms) of Epichloe typhina. Other endophytes which have been noted are a Gliocladium-like fungus in perennial ryegrass (Lolium perenne L.) and a Phialophora-like fungus in tall fescue (Festuca arundinacea Schreb.). Here, we report the identification of additional non-Acremonium sp. endophytes (herein designated p-endophytes) in three more grass species: Festuca gigantea, Festuca arizonica, and Festuca pratensis. In each grass species, the p-endophyte was cosymbiotic with an Acremonium endophyte. Serological analysis and sequence determinations of variable portions of their rRNA genes indicated that the two previously identified non-Acremonium endophytes are closely related to each other and to the newly identified p-endophytes. Therefore, the p-endophytes represent a second group of widely distributed grass symbionts. PMID- 8517750 TI - Purification and characterization of a new agarase from a marine bacterium, Vibrio sp. strain JT0107. AB - A marine bacterial strain that decomposes the cell walls of some seaweeds, including a Laminaria sp. and Undaria pinnatifida, has been isolated from seawater. This strain has been classified to the genus Vibrio. One of the enzymes which the bacteria secreted into the culture medium was isolated and purified 45 fold from the culture fluid by a combination of ammonium sulfate precipitation and successive rounds of anion-exchange column chromatography. Purified protein migrated as a single band (M(r), 107,000) on sodium dodecyl sulfate polyacrylamide gels. By amino acid sequence analysis, it was determined that this protein had a single N-terminal sequence that did not exhibit identity with the sequences of other agarases from marine bacteria. This novel enzyme was found to be an endo-type beta-agarase (EC 3.2.1.81) which hydrolyzes the beta-1,4 linkage of agarose to yield neoagarotetraose [O-3,6-anhydro-alpha-L-galactopyranosyl (1- >3)-O-beta-D-galactopyranosyl(1-->4)-O-3,6-anhydro-alpha-L-galactopy ranosyl (1- >3)-D-galactose] and neoagarobiose [O-3,6-anhydro-alpha-L-galactopyranosyl (1- >3)-D-galactose] at a pH of around 8. The optimum temperature was 30 degrees C. This enzyme did not decompose sodium alginate or lambda-, iota-, or kappa carrageenan. This enzyme may be of practical application in gene technology in the isolation of DNA fragments from agarose gels after electrophoresis. PMID- 8517751 TI - Degradation of a sodium acrylate oligomer by an Arthrobacter sp. AB - Arthrobacter sp. strain NO-18 was first isolated from soil as a bacterium which could degrade the sodium acrylate oligomer and utilize it as the sole source of carbon. When 0.2% (wt/wt) oligomer was added to the culture medium, the acrylate oligomer was found to be degraded by 70 to 80% in 2 weeks, using gel permeation chromatography. To determine the maximum molecular weight for biodegradation, the degradation test was done with the hexamer, heptamer, and octamer, which were separated from the oligomer mixture by fractional gel permeation chromatography. The hexamer and heptamer were consumed to the extents of 58 and 36%, respectively, in 2 weeks, but the octamer was not degraded. Oligomers with three different terminal groups were synthesized to examine the effect of the different terminal groups on biodegradation, but few differences were found. Arthrobacter sp. NO-18 assimilated acrylic acid, propionic acid, glutaric acid, 2 methylglutaric acid, and 1,3,5-pentanetricarboxylic acid. Degradation of the acrylic unit structure by this strain is discussed. PMID- 8517752 TI - Fate of Enterobacter cloacae JP120 and Alcaligenes eutrophus AEO106(pRO101) in soil during water stress: effects on culturability and viability. AB - A sandy loam soil near field capacity moisture content (psi = -0.050 MPa) or air dried (psi = -300 MPa) was inoculated with about 3 x 10(7) CFU of Enterobacter cloacae JP120 and Alcaligenes eutrophus AEO106(pRO101) per g and incubated in 40 g portions at 17 degrees C in closed or open Erlenmeyer flasks. In the field moist soil, selective plating, direct viable counts, and DNA hybridization showed only minor changes in the numbers of E. cloacae and A. eutrophus cells with time (14 days), and the results obtained with the three detection methods generally agreed. In the air-dried soil, the majority of both bacteria were found as intact DNA-carrying cells that were neither culturable nor viable by the methods employed in this study. The numbers of culturable E. cloacae and A. eutrophus cells dropped to 10(5) and 10(2) CFU/g, respectively, 2 h after inoculation. Direct viable counts showed that only about 1% of the cells detected by immunofluorescence microscopy were viable, but a fraction of viable nonculturable cells of both bacteria was present. A. eutrophus did not tolerate desiccation as well as E. cloacae. Only a minor fraction of the two test organisms regained their culturability or viability after rewetting of the air-dried soil; the number of total heterotrophic culturable bacteria, however, increased more than 10-fold and reached 73% of the level found in the field-moist soil at day 14. PMID- 8517754 TI - Physiological factors affecting carbon tetrachloride dehalogenation by the denitrifying bacterium Pseudomonas sp. strain KC. AB - Pseudomonas sp. strain KC was grown on a medium with a low content of transition metals in order to examine the conditions for carbon tetrachloride (CT) transformation. Several carbon sources, including acetate, glucose, glycerol, and glutamate, were able to support CT transformation. The chelators 2,2'-dipyridyl and 1,10-phenanthroline stimulated CT transformation in a rich medium that otherwise did not support this activity. Low (< 10 microM) additions of dissolved iron(II), iron(III), and cobalt(II), as well as an insoluble iron(III) compound, ferric oxyhydroxide, inhibited CT transformation. The addition of 50 microM iron to actively growing cultures resulted in delayed inhibition of CT transformation. CT transformation was seen in aerobic cultures of KC, but with reduced efficiency compared with denitrifying cultures. Inhibition of CT transformation by iron was also seen in aerobically grown cultures. Optimal conditions were used in searching for effective CT transformation activity among denitrifying enrichments grown from samples of aquifer material. No activity comparable to that of Pseudomonas sp. strain KC was found among 16 samples tested. PMID- 8517753 TI - Biotransformation of polycyclic aromatic hydrocarbons by yeasts isolated from coastal sediments. AB - Yeast abundance in the sediments of 13 coastal sites in Massachusetts was quantified, and the potential of yeast isolates to biotransform polycyclic aromatic hydrocarbons (PAHs) was determined. Plate counts of yeasts varied between 10(2) to 10(7) CFU g (dry weight) of sediment-1. The most abundant genera isolated and identified included Candida, Cryptococcus, Rhodotorula, Torulopsis, and Trichosporon. More than 50% of the isolates from heavily contaminated sites transformed phenanthrene, as determined by spray-plate screening. The plate counts of phenanthrene-transforming yeasts correlated significantly to the sediment concentrations of phenanthrene. Transformation of [9-14C]phenanthrene and [12-14C]benz[a]anthracene by individual isolates varied greatly, ranging from 0.15 to 8.15 mumol of PAH g-1 in 120-h incubations. Of the isolated yeasts, Trichosporon penicillatum exhibited the greatest capacity for phenanthrene transformation. The ability to transform PAHs appears to be widespread among yeasts in coastal sediments. PMID- 8517755 TI - Regulated expression of the nor-1 and ver-1 genes associated with aflatoxin biosynthesis. AB - RNA transcript accumulation for the ver-1 and nor-1 genes, which are associated with aflatoxin biosynthesis in the fungus Aspergillus parasiticus, was measured before and during aflatoxin production in liquid shake culture. Transcripts were not detected until near the end of trophophase (growth phase) and could still be observed well into stationary phase during batch fermentation in an aflatoxin supporting growth medium. Maximum accumulation of both transcripts occurred just prior to the onset of stationary phase. Aflatoxin B1 was first detected approximately 8 h after the appearance of the ver-1 and nor-1 transcripts. In contrast, maximum transcript accumulation for the pyrG gene (encoding orotidine monophosphate decarboxylase), which is involved in primary metabolism, was observed at the onset of trophophase when the ver-1 and nor-1 transcripts could not be detected. Accumulation of the ver-1 and nor-1 transcripts was also studied following a nutritional shift from a non-aflatoxin-supporting medium (peptone mineral salts [PMS]) to a glucose-containing medium (glucose mineral salts [GMS]), which does support aflatoxin biosynthesis. Transcripts from ver-1 and nor 1 could not be detected on PMS medium but did accumulate approximately 4 to 7 h following transfer to GMS medium. Additionally, aflatoxins were not detected in PMS medium but were observed to accumulate within 24 h after the shift from PMS to GMS. These data suggest that aflatoxin biosynthesis is in part regulated by the accumulation of the ver-1 and nor-1 transcripts. PMID- 8517756 TI - Application of rRNA-based probes for observing marine nanoplanktonic protists. AB - The use of small-subunit rRNA-based oligonucleotides as probes for detecting marine nanoplanktonic protists was examined with a ciliate (an Uronema sp.), a flagellate (a Cafeteria sp.), and mixed assemblages of protists from enrichment cultures and natural seawater samples. Flow cytometry and epifluorescence microscopy analyses demonstrated that hybridizations employing fluorescein labeled, eukaryote-specific probes intensely stained logarithmically growing protists, whereas these same protist strains in late stationary growth were barely detectable. The fluorescence intensity due to probe binding was significantly enhanced by the use of probes end labeled with biotin, which were detected by fluorescein-labeled avidin. The degree of signal amplification ranged from two- to fivefold for cultured protists in both logarithmic and stationary growth phases. Mixed assemblages of heterotrophic protists from enrichment cultures were also intensely labeled by rRNA-targeted oligonucleotide probes by the biotin-avidin detection system. Protists in late stationary growth phase and natural assemblages of protists that were otherwise undetectable when hybridized with fluorescein-labeled probes were easily visualized by this approach. In the latter samples, hybridization with multiple, biotin-labeled probes was necessary for detection of naturally occurring marine protists by epifluorescence microscopy. The signal amplification obtained with the biotin-avidin system should increase the utility of rRNA-targeted probes for identifying protists and facilitate characterization of the population structure and distribution of protists in aquatic environments. PMID- 8517757 TI - Influence of temperature and substrate concentration on bacterial growth yield in Seine River water batch cultures. AB - The growth of natural bacterial assemblages was monitored in 3-liter reactors under various temperature and substrate concentration conditions. The oxygen concentration was continuously monitored, and subsamples were taken at short time intervals to determine bacterial number and biomass. The rate of bacterial mortality was also determined. Bacterial growth yield was calculated as the ratio of net production (increase in biomass corrected for mortality) to gross production (net production plus oxygen consumption expressed in carbon units). Averaging 33%, the growth yield did not show any trend with temperatures in the range of 8 to 25 degrees C but increased with the concentration of dissolved organic carbon in the range of 2 to 12 mg of C.liter-1. PMID- 8517758 TI - Screening by polymerase chain reaction of Bacillus thuringiensis serotypes for the presence of cryV-like insecticidal protein genes and characterization of a cryV gene cloned from B. thuringiensis subsp. kurstaki. AB - Polymerase chain reaction screening using cryV-specific oligonucleotides, designed to amplify the 5' half of cryV-type genes, revealed the presence of such genes in 7 of 21 Bacillus thuringiensis serotypes examined. Restriction analysis and hybridization studies indicated that these putative genes fall into at least three subclasses. The nucleotide sequence of the cryV-type gene cloned from B. thuringiensis subsp. kurstaki DSIR732 revealed an open reading frame coding for a protein of 719 amino acids, and lysates of Escherichia coli cells expressing the 81.2-kDa CryV732 protein were toxic to Epiphyas postvittana (Lepidoptera: Tortricidae). PMID- 8517759 TI - Intraoral schwannoma. A clinicopathologic and immunohistochemical study of nine cases. AB - A clinicopathologic review was made of nine cases of benign schwannomas located in the oral cavity. The tumors arose in the vestibule (3 cases), tongue (2 cases), palate (2 cases), floor of the mouth (1 case) and lower lip (1 case). The patients included 5 women and 4 men whose ages ranged from 17 to 75 years (mean: 32.5). No patient developed recurrences. Encapsulated tumors with benign typical histology were evidenced in every case. Positive immunostaining for S-100 protein, Leu 7 antigen, vimentin and glial fibrillary acidic protein (GFAP) supported the schwann cell nature of these tumors. PMID- 8517760 TI - [Carcinosarcoma of the breast. Anatomic-clinical study of a case]. AB - The authors report the case of a 66 year old woman, who underwent surgery for carcinosarcoma of the breast. This tumour consisted of an infiltrating ductal carcinoma intermingled with sarcomatous proliferation, resembling malignant fibrous histiocytoma, without evidence of any transition between the two. Carcinosarcomas of the breast are rare tumors. Their definition and their histogenesis are discussed in the literature. Their prognosis is worse than that of metaplastic carcinomas of the breast, particularly spindle cell carcinomas, justifying precise histological classification of these biphasic tumors. PMID- 8517761 TI - [Cytological study in case of gastric leiomyoblastoma. Review of the literature]. AB - The authors describe the fine-needle aspiration cytologic features of leiomyoblastoma. Aspirated tumor cells occur singly, not in clusters. The tumor cells are globular in shape or sometimes have a spindle appearance. The nuclei are round, central or eccentric, with small nucleoli. The cells have well-defined cytoplasmic borders. The cytoplasm is abundant and, to some extent, granular, with sometimes a microvacuolar peripheral pattern. To date five cases of leiomyoblastoma with a cytological study have been published, two of them located to the stomach. A review of the literature is presented. PMID- 8517762 TI - [Fetal pulmonary candidiasis complicating mycotic chorioamnionitis]. AB - In relation to a case of pulmonary candidiasis in a seventeen week fetus, the authors review the cases of fetal candidiasis not resulting from contamination during delivery. PMID- 8517763 TI - [Value of cytological study by flow cytometry or analysis of image as a complement to macroscopic study by cytoscopy. Apropos of therapeutic follow-up of a case of tumor of the bladder]. AB - The case described corresponds to a grade G2 urothelial tumor with stage pTa extension (according to the World Health Organisation classification). After transurethral resection of the tumor and treatment by Bacillus Calmette Guerin (BCG), the efficacy of treatment was evaluated by cystoscopy, standard cytology, flow cytometry or image analysis. According to these various methods it has been shown that a normal cystoscopy may or may not be associated with aneuploidy revealed by flow cytometry. Such a case clearly illustrates the value of combining macroscopic examination and a cytologic analysis in particular by flow cytometry in order to increase the accuracy of diagnosis and to evaluate without ambiguity the efficacy of treatment. PMID- 8517764 TI - Autopsy findings in burn injuries. AB - Over a 4-year period (1986-1990) forty autopsies of burned patients were performed. The male to female ratio was 1:2.3. The age ranged between 20-95 years. (57.5% of them belonging to the 61-95 age-group). The total burn surface area ranged between 20% to 95% and 26 patients (65%) had major burns (41-95% total burn surface area). Twenty-three of our patients survived for 1 to 10 days following the accident, eleven died between days 11-40 post burn and six patients survived the 41st post burn day. Almost 70% (28 cases) of our patients presented inhalation injury, and half (20 cases) presented multiple organ failure. The most frequently affected organ was lung (38 cases), followed by heart (23 cases), kidney (17 cases) and liver (15 cases). Multiple organ failure appeared to be unrelated to the onset and efficacy of fluid replacement. The aim of our study was to demonstrate the importance of close collaboration between the clinician and the pathologist and the clinical correlation between burn autopsy and management and therapy of burn injury. PMID- 8517765 TI - Niacin in dairy and beef cattle nutrition. AB - Niacin functions metabolically as a component of the coenzymes NAD and NADP. Sources of niacin are feedstuffs and the enzymatic conversion of tryptophan and quinolinic acid into niacin. Niacin is synthesized by the microflora in the rumen of ruminants. Recent research suggests that microbial production of niacin may not be sufficient for the requirements of high producing cows. Supplemental niacin given to cows in early lactation may reduce the rate of fat mobilization, decrease the concentration of ketones in blood and increase blood glucose level. Niacin supplementation may increase propionate concentration and decrease butyrate concentration in rumen liquor. Ruminal microbial protein synthesis was enhanced by niacin. Not all experiments showed such clear results. The positive metabolic effects of niacin supplementation have resulted in most studies in an improved milk yield (3-4%) especially during early lactation. The milk constituents were mostly uninfluenced or only minimally increased. Reasons for the high variations of results are differences in ration formulation, level of milk performance, stage of lactation, age of cows, body conditions, level and duration of niacin supplementation and specific experimental conditions. Niacin supplemented cows lost less body weight during early lactation, were less days open and required fewer pellets per pregnancy. It would appear that niacin supplementation of about 6 grams per animal per day (200-400 mg per kg dry matter) for the first 60 to 100 days of lactation may be beneficial in selected high producing cows or heifers. In beef cattle niacin supplementation would appear to be beneficial (approximately 1 g per animal per day or about 100 mg per kg dry matter) when the body weight of bulls is lower than 300 kg, when the diets are poor in protein (10 tp 12% crude protein of dry matter) and during dietary adaptation periods. PMID- 8517766 TI - [The prececal digestibility of corn, sunflower, cottonseed, linseed and soybean extract meal in swine with ileocecal anastomoses]. AB - Five pigs were each surgically prepared with end-to-side (E.t.S.) and end-to-end (E.t.E.) ileorectal anastomoses (IRA). The ileo-caecal valve was preserved in both modifications. The animals were fed diets with maize or solvent extracted oil seed meals from sunflower, cottonseed, linseed or soybean and maize in combination with one of these oil seed meals. The aim of the experiment was to estimate the influence of both IRA-techniques on the precaecal nutrient digestibility and amino acid (AA) absorption. The crude carbohydrate digestibility in two of the five single protein diets and in three of the four blends were significantly higher in the E.t.S.--than in the E.t.E.--IRA group. There were no significant differences between the two IRA-modifications in crude protein (CP) and crude fat digestibility. No differences were observed in AA absorption for the single components maize, sunflower- and cottonseed meal. The absorption values of isoleucine, leucine and valine from linseed meal were significantly more than 5%-units higher in the E.t.S.-group than in E.t.E. animals. There were similar results in soybean meal for four essential AA but with differences below 5%-units. Accordingly the two IRA-modifications did not influence the AA absorption to a practically important extent. PMID- 8517767 TI - [The effect of feeding frequency on the results of metabolism-oriented lysine requirement determination and nitrogen balance in broiler chicks]. AB - Two feeding regimes were used for investigation into the effect of meal frequency on the lysine requirement in chickens estimated with metabolism-oriented determination. 1-day-old male broiler chickens were fed either twice a day for 1 hour (one group) or 6 times a day for 1/2 hour (other group). 7 to 21 days posthatching the birds received a wheat-wheat gluten diet which was L-lysine supplemented at 6 levels. Using lysine deficient diets chickens fed twice a day eat more and grow faster than chickens fed 6 times a day. The N-balance was 6 to 7% higher in the case of the feeding regime 2 times a day. After feeding period 14C-U-L-lysine was injected intravenously and 14CO2-excretion measured. The estimated range for lysine requirement was 11.9-13.1 g lysine/kg DM and 13.1-14.3 g lysine/kg DM for chickens fed 2 times and 6 times a day, respectively. A feeding regime of 6 meals a day does not improve the utilization of diets contains crystalline lysine compared with feeding of 2 meals a day. PMID- 8517768 TI - [The use of native triticale in poultry. 3. Use in laying hens]. AB - In three trials with a total of 3240 white laying hybrids, 10 to 72% Triticale of the variety "Grado" was used as a substitute for maize and wheat. The feeding of Triticale had no influence on feed consumption, laying performance, feed efficiency, mortality or weight gain. In two of three trials the egg weight was lowered with an increasing amount of Triticale in the diet. After supplementation of 1 or 1.5% sunflower oil to the diets with 50 resp. 72% Triticale the egg weight increased again to the level of the control group. With the exception of one group, there was no correlation between breaking strength and deformation of the eggs. The colour intensity of the egg yolk was decreased with increasing amounts of Triticale in the diet. It can be concluded, that laying hen feed supplemented with oil may contain up to 50% Triticale, but in non-supplemented diets the highest amount of Triticale should be only 20% because of the risk of linoleic acid shortage. PMID- 8517769 TI - The effect of supplementary formalin treated soya-bean meal on feed intake, milk yield and live-weight gain of dairy cows fed ensiled fodder beets. AB - The present experiment compared formalin treated soya-bean meal (2 kg DM) with barley and urea (2.4 kg DM) as supplements for a mixture of ensiled beets and ammonium-treated straw given ad libitum in a cross over experiment with two periods of 6 weeks. Furthermore, these diets were compared to a traditional diet with fodder beets and ad libitum feeding with grass silage for a period of 12 weeks. The soya-bean meal increased the daily intake of beet-straw silage significantly from 13.1 to 14.1 kg DM (P < 0.01), the yield of milk protein (from 775 to 803 g; P < 0.05) and the live-weight gain (from 138 to 400 g; P < 0.05). Compared to the traditional diet, in which the total energy intake was close to that of the beet-straw silage diets, milk and protein yield (but not milk fat yield) were lower by the beet-straw silage feeding, although not significantly. However, this response seems to be typical and may indicate that not only the amino acid supply of the cows but also the supply of other glucogenic nutrients may be adversely affected when feeding ensiled beets. PMID- 8517770 TI - [Comparative studies of feed consumption, performance data and physiologic values among cows with high and low milk protein content]. AB - One high protein group (HE) and one low protein group (NE) were formed from cows differing greatly in milk protein content out of 12 feeding trials. The differences between both groups were insignificant resp. not well defined in the parameters of the feed intake, energy conversion, development of live weight and the physiological parameters, so that suppose, cows with high or low milk protein content do not differ in the investigated parameters. As a possible characteristics feature the titer of free amino acids in blood serum is indicated. PMID- 8517771 TI - [Digestion, growth and body composition of carp (Cyprinus carpio L.) after feeding different starch varieties]. AB - Maize starch (treatment I), pregelatinized maize starch (II), wheat starch (III), pregelatinized wheat starch (IV), potato starch (V) or manioc meal (VI) were mixed in portions of 41% (I-V) or 46.7% (VI) to a basal diet. Each experimental diet was fed to 33 carp (Cyprinus carpio L.) (three aquaria with 11 carp each) in a daily amount of 1.8-2.0% of live weight. The experiment lasted 118 days and the carp had a mean live weight of 146 g at the beginning. The diets I-IV had a similar, high energy digestibility of about 90%, whereas the diet with potato starch and the diet with manioc meal significantly lowered the digestibility of the energy to 85% or 87%. The growth and the feed expenditure were not influenced by the different starches. The carp had a mean final weight of 520 g. All carcasses had, on average, a content of ash, protein, fat and energy of 2.8%, 15.7%, 9.4% and 7.4 kJ per g fresh matter. However, potato starch and manioc meal distinctly reduced the energy retention in comparison to maize and wheat starch (diet I or III) because the contents of dry matter, fat and energy of the carcasses of these carp were significantly lowered. PMID- 8517772 TI - [Lowering of the nitrogen excretion in swine]. AB - Because of the low efficiency of N utilisation, animal husbandry is the main contributor of N pollution into environment within agricultural production systems. Possible solutions are to regulate the fertilizing and animal stocking rate per hectare as well as improving the efficiency of N utilisation in animal nutrition. Production of pig manure is determined by the kind of animal production, feeding level, performance level and N intake. Increasing performance improves nutrient utilisation which in turn reduces the amount of manure and manure-N per production unit. N intake especially influences N excretion. Therefore feeding in exact relation to the requirement is most important for an ecological pig husbandry. The proportion of the easily soluble urinary N to faecal N can be lowered by diet composition, mainly by higher amounts of bacterial fermentable substances. Thereby the ecological quality of manure is improved. Lowering of excessive N excretion in pigs via feeding measures is possible in two ways, (1) by exact adaptation of the protein supply in agreement with the changing requirements and (2) by improving the dietary amino acid balance. In the first case N excretion in fattening pigs and sows can be reduced up to 12%. In the second case lowering dietary protein and supplementation with crystalline amino acids diminished N emission up to 40% to 50%, practically achievable are under present conditions about 20%. PMID- 8517773 TI - [Use of 15N-labeled lysine for the determination of fractional protein synthesis rates by the flooding method]. AB - The fractional synthesis rates (FSR) for liver, pancreas, small intestine, large intestine, skeleton muscle and whole body protein were estimated with the help of the large dose method of McNurlan et al. (1979) and Garlick et.al (1980) using simultaneously [14C]lysine and [15N]lysine as flooding substances in growing rats. The following results and conclusions can be drawn: In the case of lysine as flooding substance the incorporation time (time from the injection up to killing the animals) can be fixed at 20 minutes. On principle lysine is suitable as flooding substance. [14C]lysine and [15N]lysine can yield identical values for FSR in the same animal. The variation coefficients of the FSR values were 7.3% (4... 12%) using [14C]lysine and 13.8% (9.5... 36%) using [15N]lysine (emission spectrometry) as flooding substance. Using the mass-spectrometric method for measuring 15N-excess it is possible to obtain the same accuracy of result as in the case of estimation [14C]lysin. The main advantage of using 15N-labelled amino acids as flooding substances is the absence of any radioactivity. Therefore this method is also suitable for farm animals and--in combination with the indolent muscle biopsy--it may be used for men. PMID- 8517774 TI - [Methodical studies of metabolism oriented methionine requirement determination in broiler chicks. 2. Effect of feeding frequency on methionine utilization]. AB - The effect of feeding frequency (daily 2 times feeding for 1 hour or 6 times feeding for 30 minutes) and a different methionine content of the diet on weight gain, N-balance and metabolic 35S-methionine degradation was investigated in broiler chickens. Weight gain and N-balance were not improved by increased feeding frequency. At the high feeding frequency, weight gain and N-balance were even depressed when diets with methionine deficiency (without methionine supplementation) were fed. No effects of feeding frequency and the amount of DL methionine supplementation on the level of excreted 35S after i.v. injection of 35S-methionine were observed. PMID- 8517775 TI - [The protein turnover of different leghorn hybrids]. AB - After N-balance experiments with leghorn-hens of five different genetic origins in the top laying period, the advanced laying period as well as at the end of the laying period and with feeding of soybean meal/fish meal protein, the nitrogen maintenance requirement per live weight kg0.67 was ascertained regressively by approximation of the N-balance from N-increasing experiments to an exponential function. The Net Protein Utilization (PNu) curve and the apparent Net Protein Utilization (PEW) curve could be described as utilisation values from the N retention curve (e-function). Moreover the relation between N-intake/LW kg0.67 and egg-N-discharge/LW kg0.67 from N-balance made it possible to estimate N retention in the body. Finally, capability of the five origins at equal protein and S-AA intake respectively were compared. PMID- 8517776 TI - [The effect of flavomycin on digestion in fattening bulls]. AB - Three friesian bulls (Genotype 31) were fitted with re-entrant cannulas at the duodenum to investigate the influence of a flavomycin supplement of the digestion in the forestomachs and the other parts of the digestive tract. The supplement of flavomycin increased the total digestibility of the organic matter. The digestibility of starch and sugar was between 97% and 98%. The balance of the nutrients in the digestive tract shows, that by flavomycin supplementation the degradation of organic matter and crude protein in the fore stomach was decreased and the amount of the organic matter and crude protein in the gut was increased. The balance of the amino acids in the gut showed that after flavomycin ca. 30 g more amino acids were found in the gut. The synthesis of bacterial protein in the forestomachs was, after flavomycin application, slightly reduced as was the degradation rate of the feed protein. PMID- 8517777 TI - [The effect of flavomycin on the fattening performance of bulls]. AB - An experiment with 36 fattening friesian bulls was conducted to investigate the effect of flavomycin (50 mg/d.animal). The additional flavomycin significantly enhanced the apparent digestibility of the organic matter, crude fibre and NFE. The animals in the experimental group consumed significantly more feed than the controls until the 56th day of the experiment. No appreciable differences between the two groups occurred thereafter. The daily gain of the animals in the experimental group was always higher than that of the controls except from day 140 to day 168 of the experiment. The mean daily gain for the animals in the control group was 949 g, whereas for those in the control group it was 916 g. This difference is statistically significant. The daily gains of the experimental animals were 3.5% higher than those of the controls. The animals receiving flavomycin tended to need a lower energy input than the controls. The control animals had a mean requirement of 3.80 kEFr/kg gain compared with 3.68 kEFr/kg for the experimental animals. This corresponds to a 3.2% improvement in energy conversion. As far as slaughter performance was concerned, the additional flavomycin had no effect on carcase composition, organ weight and chemical composition. Only the internal fat fraction was increased somewhat by flavomycin. The flavomycin had no influence on the fatty acid composition in the rumen. In particular, the ratio of acetic acid to propionic acid was unchanged. A trend to a slight increase in the total fatty acid concentration was observed. The treatment did not affect the number of protozoa in the rumen. PMID- 8517778 TI - Thymocyte apoptosis as a mechanism for tributyltin-induced thymic atrophy in vivo. AB - Tributyltin (TBT) immunotoxicity in rodent species is primarily characterised by T-lymphocyte deficiency resulting from a depletion of cortical thymocytes. In this study, bis(tri-n-butyltin) oxide (TBTO) was administered to male rats as a single oral dose of 30 or 60 mg/kg, and assessments were made of thymic cytopathology and the integrity of cellular DNA. TBTO treatment did not cause severe toxicity or overt clinical signs; however, by 48 h post-dosing relative thymus weights at 30 and 60 mg/kg were reduced to 66 and 43%, respectively, of control values. Increased DNA fragmentation was evident in thymic cell isolates (principally thymocytes) obtained from treated animals during the period of thymic involution. When DNA purified from these cells was visualised by agarose gel electrophoresis a multimeric internucleosomal fragmentation pattern, indicative of supra-physiological levels of apoptosis, was detected. Although unassociated apoptotic or necrotic thymocytes were essentially absent in cell preparations from TBTO-treated rats, significantly increased numbers of mononuclear phagocytic cells were observed. Many of these cells contained either apoptotic thymocytes, with nuclear morphologies exhibiting chromatin condensation, or cell remnants which were characterised as apoptotic bodies. Dibutyltin, which is a major metabolic dealkylation product of tributyltin, failed to significantly stimulate apoptosis when added to isolated thymocytes in vitro. Collectively, these findings suggest that activation of apoptosis contributes to TBT-induced thymocyte depletion in vivo, and indicate that it is unlikely that the metabolite dibutyltin is responsible for this effect. PMID- 8517779 TI - Exposure to various benzene derivatives differently induces cytochromes P450 2B1 and P450 2E1 in rat liver. AB - Benzene (B), toluene (T), ethylbenzene (EB), styrene (S) and xylene isomers (oX, mX, pX) are important environmental pollutants and B is a proved human carcinogen. Their inhalation by male Wistar rats (4 mg/l, 20 h/day, 4 days) caused cytochrome P450 (P450) induction. The degree of P450 2B1 induction increased and that of 2E1 decreased in the series B, T, EB, S, oX, mX and pX, as estimated by Western blots, while neither solvent was as effective for 2B1 induction as phenobarbital and B was more effective for 2E1 than ethanol. The levels of several other P450s decreased after exposure to these solvents, B being most effective. Exposure to these solvents increased in vitro hepatic microsomal oxidation of B and aniline (AN) (2E1 substrates) 3 to 6-fold, indicating induction of this P450. T oxidation was increased 2 to 4-fold and chlorobenzene (ClB) oxidation 3-fold. Sodium phenobarbital (PB, 80 mg/kg/day, 4 days, i.p.) did not increase ethylmorphine (EM) and benzphetamine (BZP) demethylation (2B1 substrates), neither of the B derivatives did so, and oX decreased it; however, pentoxyresorufin O-dealkylation was well related to the immunochemically detected 2B1 levels in control, PB and B microsomes. PB did not increase B, but increased T and ClB oxidation 2-4 and 3-fold, respectively, indicating possible 2B1 role in their oxidation. B oxidation after various inducers was related to immunochemical 2E1 levels, T and ClB oxidation to both 2B1 and 2E1 and AN oxidation to 2E1 and 1A2 levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517780 TI - Investigations into the effects of various hepatotoxic compounds on urinary and liver taurine levels in rats. AB - The effect of various hepatotoxicants on urinary taurine and urinary creatine has been studied in the rat. Several hepatotoxic agents, carbon tetrachloride, thioacetamide, galactosamine and allyl alcohol which all caused hepatic necrosis (sometimes accompanied by steatosis), resulted in a rise in urinary taurine and in some cases creatine, when administered to rats. Ethionine and hydrazine also raised urinary taurine but caused only steatosis and did not raise urinary creatine. Therefore urinary taurine and possibly creatine may be useful markers of liver injury and dysfunction. Liver taurine levels were also affected by some of the hepatotoxicants but in those cases where there was a rise in urinary taurine this could not be accounted for by the loss in liver taurine. It is suggested that the increase in urinary taurine is partly due to changes in protein synthesis and hence in sulphur amino acid metabolism caused by hepatotoxic agents. However, bromobenzene did not increase urinary taurine and alpha-naphthylisothiocyanate and lithocholate caused reduced levels. It is suggested that this lack of increase in urinary taurine may be due to depletion of glutathione or interference with the biliary system. PMID- 8517781 TI - Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells. AB - The effects of the herbicides fomesafen, oxyfluorfen, oxadiazon and fluazifop butyl on porphyrin accumulation in mouse liver, rat primary hepatocyte culture and HepG2 cells were investigated. Ten days of herbicide feeding (0.25% in the diet) increased the liver porphyrins in male C57B1/6J mice from 1.4 +/- 0.6 to 4.8 +/- 2.1 (fomesafen) 16.9 +2- 2.9 (oxyfluorfen) and 25.9 +/- 3.1 (oxadiazon) nmol/g wet weight, respectively. Fluazifop-butyl had no effect on liver porphyrin metabolism. Fomesafen, oxyfluorfen and oxadiazon increased the cellular porphyrin content of rat hepatocytes after 24 h of incubation (control, 3.2 pmol/mg protein, fomesafen, oxyfluorfen and oxadiazon at 0.125 mM concentration 51.5, 54.3 and 44.0 pmol/mg protein, respectively). The porphyrin content of HepG2 cells increased from 1.6 to 18.2, 10.6 and 9.2 pmol/mg protein after 24 h incubation with the three herbicides. Fluazifop-butyl increased hepatic cytochrome P450 levels and ethoxy- and pentoxyresorufin O-dealkylase (EROD and PROD) activity, oxyfluorfen increased PROD activity. Peroxisomal palmitoyl CoA oxidation increased after fomesafen and fluazifop treatment to about 500% of control values both in mouse liver and rat hepatocytes. Both rat hepatocytes and HepG2 cells can be used as a test system for the porphyrogenic potential of photobleaching herbicides. PMID- 8517782 TI - Transport characteristics of paraquat across rat intestinal brush-border membrane. AB - The mechanism of absorption of paraquat, which is a type of quaternary ammonium compound (QAC), was studied using rat intestinal loops and brush-border membrane vesicles. Approximately 47% and 37% of radioactively labeled paraquat injected into jejunal and ileal loops disappeared, respectively, after 60 min. Since only a small amount of radioactivity was detected in the mucosal fraction, most of the paraquat that disappeared from the intestinal lumen was considered to have been carried away by the bloodstream, indicating that paraquat absorption was greater than expected. In spite of its low lipid solubility, the uptake of paraquat by brush-border membrane vesicles reflected smooth penetration into the intravesicular space rather than binding to the membrane. According to the increase in extravesicular paraquat concentration, paraquat uptake in the early stage was saturable. Moreover, early paraquat uptake was significantly inhibited by structurally-related QACs such as tetramethylammonium and choline, but not by an endogenous dicationic amine (putrescine). On the other hand, inside-negative membrane potential had no significant effect on the time course of paraquat uptake. From these results, it is suggested that paraquat is absorbed through a specialized mechanism associated with the carrier-mediated transport system for choline on the brush-border membrane. PMID- 8517783 TI - Identification and partial characterization of a glycoprotein species with high affinity for methylmercury in peripheral nervous tissues of man and experimental animals. AB - A small amount of a glycoprotein species (21-kDa glycoprotein) with high affinity for methylmercury (MeHg) was detected in the post-nuclear or post-mitochondrial supernatant fraction of the homogenate of rat sciatic nerve on electrophoresis and autoradiography after binding of Me203Hg to the fraction. The 21-kDa glycoprotein was also found in the subcellular fractions of mouse, hamster, guinea pig, rabbit and human peripheral nervous tissues. Experiments with the cellular fractions of the tissues revealed that the 21-kDa glycoprotein is localized mainly in the myelin fraction, whereas it was not found in the cellular fractions of brain, spinal cord and nonneural tissues, such as kidney and liver. The specific binding activity of the 21-kDa glycoprotein with MeHg was 12-15 fold that of the major myelin protein, Po. It was shown that the interaction of the 21 kDa glycoprotein with MeHg was mediated through sulfhydryl groups in experiments with iodoacetamide and dithiothreitol. The amino acid compositions of the rat and human 21-kDa glycoproteins were similar but very different from that of a typical metallothionein. The N-terminal amino acid sequences of the two components of the rat 21-kDa glycoprotein were identical to those of P0 and PMP-22, respectively. The in vitro binding of MeHg was also observed in the myelin fraction obtained from the sciatic nerves of MeHg-dosed rats. PMID- 8517784 TI - Effect of exposure to 2,5-hexanediol in light or darkness on the retina of albino and pigmented rats. I. Morphology. AB - Male albino (Sprague Dawley) and pigmented (Norwegian Brown) rats received 1% 2,5 hexanediol (H) in their drinking water for 5 or 8 weeks, respectively. The rats were housed either in 12 h light (average 30 cd/cm2 inside cage) and 12 h darkness (group LH) or in total darkness (group DH). Two control groups (Light only, LC; Darkness only, DC) were studied in parallel under identical conditions. The animals were sacrificed at the end of H exposure or after an ensuing 13-week period without H but under the same lighting conditions. The retinas of albino rats in the LH group showed a reduction (compared to the LC, DH and DC groups) in the number of nuclei per unit area of the outer nuclear layer (ONL; p < 0.05) and degeneration of the outer segment and the inner segment layers (photoreceptor cells). A less pronounced loss of nuclei was seen in the LC group. No decrease in the number of nuclei, or signs of degeneration, were demonstrated in the albino DH or DC groups. Thirteen weeks after exposure to H, the albino LH rats had lost about 50% of the nuclei in the ONL (p < 0.05) and the outer plexiform layer (OPL) had almost disappeared. At the corresponding time, in the pigmented rats the LH and DH groups differed from the LC and DC groups. The degenerative process resulted in no inflammatory changes in the retina. The results imply an interaction exceeding simple summation after exposure to light and H, in destroying photoreceptors and OPL (p < 0.001) in albino rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517785 TI - Metabolism and distribution in the rat of peak E substance, a constituent in L tryptophan product implicated in eosinophilia-myalgia syndrome. AB - Peak E substance, 1,1'-ethylidenebis[tryptophan], a contaminant found in L tryptophan tablets, has been suggested as a causative agent for eosinophilia myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C8 cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5 24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 micrograms, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro-beta carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than in L-tryptophan-treated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than from L-tryptophan. Finally, we propose acetaldehyde-induced production of MTCA from peak E substance. PMID- 8517786 TI - Accumulation of 1-methyl-tetrahydro-beta-carboline-3-carboxylic acid in blood and organs of rat. A possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. AB - 1-Methyl-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) may cause eosinophilia-myalgia syndrome (EMS) associated with ingestion of L-tryptophan. The distribution and excretion of MTCA were studied in rats which had received perorally a single 1.6 mg/kg dose of MTCA. MTCA concentrations in blood, kidney, liver, brain, heart, spleen, lung and gastrocnemius muscle were measured by HPLC combined with fluorometric detection. The concentration of MTCA in each organ reached a maximum at 1 h and then gradually declined. However, a significant level of MTCA still remained at 5 h, when 52% of ingested MTCA remained in the contents of the large intestine. Twenty-nine percent of the ingested MTCA was excreted in urine over the course of 24 h. A higher dose (10 mg/kg) of MTCA resulted in significant elevations in the concentrations and amounts of MTCA in the various organs. In addition, chronic treatment with a 10 mg/kg dose of MTCA for 6 weeks further increased the concentrations and amounts of MTCA in each organ. However, no histological changes were observed in any of the organs after chronic treatment. This is the first report which demonstrates accumulation of MTCA in the blood and various organs, including muscle, of rats. PMID- 8517787 TI - On the enzyme-inducing action of calcium antagonists. AB - The effects of three calcium antagonists, nifedipine (NF), verapamil (V) and diltiazem (DL), on rat liver monooxygenases were studied. The drugs were administered in oral doses of 50, 40 and 30 mg/kg daily for 3 weeks in male Wistar rats. NF and V shortened the hexobarbital (HB) sleeping time and increased benzphetamin-N-demethylase (BND), ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), ethoxyresorufin-O deethylase (EROD) and NADPH-cytochrome c reductase activities and the content of cytochrome P-450 and microsomal heme, but did not change the content of cytochrome b5. The data suggest that these calcium antagonists exert an enzyme inducing effect on the hepatic monooxygenases. DL significantly increased only the EROD and NADPH-cytochrome c reductase activities and shortened HB sleeping time to a lesser extent, suggesting a weaker enzyme-inducing effect as compared to NF and V. The three drugs increased the delta-aminolevulinic acid (ALA) synthetase activity and decreased heme oxygenase (HO) activity. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein. PMID- 8517788 TI - Construction of an infectious DNA clone of the Y1 strain of canine parvovirus and characterization of the virus derived from the clone. AB - We have cloned genome fragments of canine parvovirus strain Y1 from replicative form DNA and double-stranded DNA synthesized from virion DNA in vitro, and constructed a recombinant plasmid containing a full-length Y1 genome (pCPVY 1). When this recombinant plasmid was transfected into cell cultures, an infectious virus could be recovered. To characterize this pCPVY 1-derived virus, its biological properties were compared with those of the parental strain. No difference was observed between them in antigen expression, viral DNA replication, hemagglutination ability, and virus multiplication, indicating that the virus derived from the infectious plasmid inherited the biological properties of the authentic Y1 strain. Therefore, this recombinant plasmid appears to be useful for reverse genetics of canine parvovirus. PMID- 8517789 TI - Immunodetection of the plum pox virus helper component in infected plants and expression of its gene in transgenic plants. AB - Tobacco plants (Nicotiana tabacum cv. Xanthi) have been transformed via Agrobacterium tumefaciens vectors, with cDNAs corresponding to the plum pox virus (PPV) cistron 2 encoding helper component (HC-Pro) and with the first two and half cistrons of the PPV genome. Presence of the HC-Pro in PPV-infected plants and transgenic plants transformed with the gene coding for this protein was investigated using specific polyclonal antibodies produced against the PPV HC Pro. The results suggest that two proteases are involved in the processing of the PPV N-terminal polyprotein to yield a protein of 48 k (HC-Pro). HC-Pro autolytically cleaves at its carboxyl-terminus and a proteolytic activity, probably associated with the protein (P1) encoded by the cistron 1, is required for the cleavage in planta between the proteins derived from cistrons 1 and 2. PMID- 8517790 TI - Protected endogenous retroviral sequences copurify with infectivity in experimental Creutzfeldt-Jakob disease. AB - Scrapie and Creutzfeldt-Jakob disease (CJD) are caused by infectious agents that are defined phenomenologically. No agent-specific molecules or particles have been identified. Biological properties, such as exponential agent replication and strain variation, as well as physical characteristics of infectivity indicate a protected viral structure. A host membrane glycoprotein of 34 kDa ("prion" protein) that aggregates at end stages of disease is clearly important in pathology and susceptibility to infection, but has no demonstrable infectivity in any purified or recombinant form. Thus a characterization of more viral-like molecules is important. In order to identify viral-like nucleic acids we previously developed methods to substantially purify the human CJD agent from experimentally infected hamster brains, and demonstrated selected retroviral-like LTR bands at pg levels that were insufficient for sequencing. To further define these and other viral-like sequences we cloned nucleic acids from highly infectious CJD fractions, and tested the efficacy of our methods using a selected retroviral probe. RNA extracted from an infectious 120 S Gaussian peak, which is reproducibly purified approximately 100,000 fold with respect to starting nucleic acids, and contains approximately 20% of the initial brain infectivity, was used to generate a cDNA library in a sequence independent amplification strategy for low levels of RNA (< 6 ng). Reconstituted strong stop experiments using several retroviral tRNA primers had indicated that Syrian hamster IAP (SHIAP) sequences should be present in both CJD and uninfected control fractions. Because SHIAP particles are extremely resistant to denaturation, their representation in a cDNA library would imply adequate extraction of other protected RNAs of viral origin. At least 900 bases of the Syrian hamster retroviral IAP genome were unambiguously identified in the cDNA library, and in independent PCR walks with selected primers, all of which were based on our cloned sequences. Sequencing confirmed the presence of protected LTR and adjacent retroviral motifs. Because these sequences were also present in control preparations they may represent normal endogenous viral contaminants that cosediment with infectivity in size and density gradients. On the other hand, LTRs can drive the expression of many diverse sequences, and it remains to be seen if CJD specific sequences are either transduced, or copackaged with, protected IAP complexes. The effective extraction and amplification of highly protected SHIAP nucleic acids of significant length sets the stage for identifying additional protected viral elements that may specify the CJD agent. PMID- 8517791 TI - A comparative study of the effect of dextran sulfate on the fusion and the in vitro replication of influenza A and B, Semliki Forest, vesicular stomatitis, rabies, Sendai, and mumps virus. AB - The effect of dextran sulfate on the fusion of a series of enveloped viruses, bearing specifically different fusion proteins, was investigated. The fusion with model- and with biological membranes was monitored by an R18 fluorescence dequenching fusion assay. Dextran sulfate strongly suppresses the fusion of orthomxyo- (influenza A (H1N1 and H3N2 subtypes) and influenza B), of toga- (Semliki Forest virus), and of rhabdoviruses (vesicular stomatitis and rabies virus). The fusion of the paramyxo-viruses Sendai and mumps was not significantly affected by the anionic polysaccharide. The response to dextran sulfate was virus specific, and identical for the different members of one virusfamily, bearing the same fusion protein. It was shown that dextran sulfate attaches with high affinity to the viruses studied, but not to erythrocytes. The anionic polymer appears to attach to the fusion epitope of the viral membrane. The inhibition of virus replication in vitro shows a remarkable correlation with the observed anti fusion effects of dextran sulfate. PMID- 8517792 TI - The prevalence of antibodies to human T-lymphotropic virus type I in different population groups in Papua New Guinea. AB - Isolation and partial sequencing of human T-lymphotropic virus type I (HTLV-I) variants from inhabitants of Papua New Guinea (PNG) and the Solomon Islands has confirmed the existence of virus infection in Melanesian populations. To determine the geographical distribution of seropositivity to HTLV-I in PNG we have tested 2907 serum and plasma samples collected between 1972 to 1991 from 16 different population groups. Samples were screened using a particle agglutination assay and confirmed by p21e-enhanced Western immunoblot (WB). From a total of 94 screen positive samples run on WB, 56 (60%) were confirmed positive (positive for both env and gag products) and 38 (40%) were WB-indeterminate (gag products only). The prevalence of WB-confirmed antibodies to HTLV-I in lowland and island populations ranged from 0 to 5.4%. There were no confirmed antibody positives in the highland populations surveyed. Geographically isolated populations living on the fringes of the highlands ranged in seropositivity from 0.2 to 5.8%. Two of the subjects surveyed gave WB antibody patterns characteristic of HTLV-II rather than HTLV-I infection. PMID- 8517793 TI - Protective immunity of Hantaan virus nucleocapsid and envelope protein studied using baculovirus-expressed proteins. AB - Recombinant Hantaan virus nucleocapsid protein (rNP) and recombinant envelope (rEnv) proteins were prepared using a baculovirus expression system to examine the role of Hantaan virus structural proteins in protective immunity. Passive transfer of spleen cells from mice immunized with rNP conferred partial protection or prolongation of time to death from fatal Hantaan virus infection in suckling mice which were challenged with Hantaan virus at 40 LD50 (survival rate: 43%) or 4 LD50 (survival rate: 43%). The T cell-enriched fraction protected one mouse from lethal infection but the B cell-enriched fraction had no such effect on fatal HTN infection. The protective effects of the antibody against HTN challenge were examined by passive immunization. The monoclonal antibody ECO 2 directed to NP also conferred partial survival and significant difference in time to death. Although rEnv antigen failed to induce neutralizing antibody, both immune spleen cells and immune serum to rEnv conferred partial protection upon suckling mice. These results indicate that both nucleocapsid and envelope proteins of Hantaan virus were responsible for induction of cell mediated protective immunity. Vero E 6 cells infected with Hantaan virus expressed envelope protein on the surface, as determined by flow cytometry. However, there was only negligible expression of nucleocapsid protein. PMID- 8517794 TI - Physicochemical properties and cytopathogenicity of an adenovirus-like agent isolated from corn snake (Elaphe guttata). AB - A virus isolated from the internal organs of a moribund corn snake (Elaphe guttata) replicated in reptilian cell cultures (IgH-2, TH-1 cells) between 10 and 30 degrees C. Highest infectivity titers of 10(5.5) TCID50/ml were obtained in IgH-2 cells at 25 degrees C. Infected IgH-2 cells showed the development of three morphologically different intranuclear inclusion bodies. During viral assembly the particles formed typical crystalline aggregates in the nucleus. About 64 h after infection progressive desintegration of the nuclear membrane was evident and virus particles were released into the cytoplasm. Different fish cell lines (CLC, CHSE-214, BF-2, PG, RTG-2) were not capable of propagating the virus. The DNA containing agent proved to be stable at pH3, more or less at pH 12 and to treatment with chloroform, but it was rapidly inactivated at 56 degrees C. Electron microscopy revealed nonenveloped icosahedral particles with a diameter of 65-70 nm. PMID- 8517796 TI - MDBK cells which survived infection with a mutant of influenza virus A/WSN and subsequently received many passages contained viral M and NS genes in full length in the absence of virus production. AB - From a variant of MDBK cell line carrying the nucleotide sequences specific to a mutant of influenza virus A/WSN, we obtained cDNA clones representing viral M and NS genes in full length by polymerase chain reaction (PCR). The sequence analysis of five cDNA clones each for the respective genes revealed 4 to 10 base changes with M and 2 to 6 with NS compared with the corresponding genes of the original virus, although it was possible that at least some of them were ascribed to the artifacts during reverse transcription or Taq polymerase reaction. PMID- 8517795 TI - Use of FITC-labeled influenza virus and flow cytometry to assess binding and internalization of virus by monocytes-macrophages and lymphocytes. AB - The binding of influenza virus to the surface of cells and the internalization of virus particles by all or a subset of cells are key points in the pathogenesis of viral infection. The current studies established a method for discrimination of surface-bound from internalized influenza virus. Fluorescein isothiocyanate (FITC) was attached to the viral hemagglutinin and neuroaminidase proteins; the fluorescent virus retained infectivity. A flow cytometric technique was then adapted for study of virus-cell interactions, with addition of ethidium bromide to quench green fluorescence associated with FITC-labeled virus that was cell bound but remained external. Ethidium bromide was excluded by intact cell membranes, and internalized virions retained green fluorescence. Cells could be examined by fluorescence microscopy or flow cytometry, with flow cytometry allowing rapid, kinetic assessment of large numbers of cells and subsets of virus exposed cells. The data showed that, whereas a majority of both monocytes macrophages and lymphocytes bound influenza virus, a large percentage of monocytes-macrophages but only a very small percentage of lymphocytes internalized the virus. This procedure provides a simple and effective method to distinguish surface-bound from internalized influenza virus, and allows precise kinetic analyses on large numbers of cells. PMID- 8517798 TI - Specific tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture. AB - Among all the neural cells in fetal rat brain culture developing neurons showed the highest rate of infection by Japanese encephalitis virus (JEV). JEV specifically bound to these cells as measured by immuno-staining. These results indicate that developing neurons are the major target of JEV, and that the initial specific binding of virus to these cells may be one of the reasons for the neurotropism of JEV. PMID- 8517797 TI - Phagocytosis reduces HIV-1 production in human monocytes/macrophages infected in vitro. AB - The addition of ingestable particles (opsonized erythrocytes or latex beads) or a phorbol ester activates monocytes--derived human macrophages (MDHM) cultured in vitro, and markedly reduces virion release from HIV-infected MDHM as well as their ability to transmit the infection to cocultured lymphoid CD4-positive CEM cells. PMID- 8517800 TI - Alterations of muscle activities and jaw movements after blocking individual jaw closing muscles in the miniature pig. AB - Although the inactivation or removal of motoneurones and muscles are known to affect development and growth of the craniofacial skeleton and masticatory muscles, the effect of these on functional activity patterns is not clear. The goal of this study was to evaluate the immediate responses of masticatory muscle activities to temporary nerve blocks of individual jaw-closing muscles. Nineteen experiments were made with four miniature pigs (Sus scrofa). Electromyograms of the masticatory muscles and jaw movements were recorded during natural chewing. Then, the function of individual jaw-closing muscles was removed unilaterally by local anaesthesia, and the recording repeated. The results showed a general increase in the activities of the other jaw-closing muscles, particularly those that were synergistic with the blocked muscle in producing lateral movements. Furthermore, the lateral pterygoid showed stronger activity, and accordingly the lateral movement was increased. Digastric muscle activity and the magnitude of jaw opening also tended to increase. Thus, the response to loss of a muscle is a strong, immediate compensation by synergists. PMID- 8517799 TI - Salivary proteolysis of histidine-rich polypeptides and the antifungal activity of peptide degradation products. AB - Incubation of purified synthetic histidine-rich polypeptides, HRP-2, -3, -4, -5, 6 (histatins), with diluted human parotid saliva yielded a series of peptide degradation products whose structures could be determined by gas-phase sequencing of cationic polyacrylamide gel electroblots. Sequencing indicated that two and sometimes three peptides were present in the same Coomassie blue-stained band. By comparing different individuals' salivas it was observed that structural variation occurs, perhaps due to differences in the concentrations or specific activities of salivary proteases. Based on the structural data, four proteolytic enzyme activities are proposed. A trypsin-like and chymotrypsin-like enzymatic activity(s) appear to represent the most active salivary protease; however, both an alanine-lysine endopeptidase and a histidine peptidase activity are also present in parotid saliva. In comparison to HRP-4 or HRP-6, degraded products were less active as antifungal agents against Candida albicans both in blastospore and germ-tube assays. PMID- 8517801 TI - Immunohistochemical demonstration of androgen receptors in human salivary glands. AB - Androgen receptors were demonstrated in human salivary glands by immunohistochemistry using polyclonal antibodies. Fresh, clinically healthy salivary gland samples (two from minor, seven from parotid and eight from submandibular glands) of both sexes were used. Frozen tissue sections were incubated with the antibody against human androgen receptor and visualized by an indirect immunoperoxidase technique. Androgen receptors could be detected in all salivary tissues studied. Positive staining was confined to nuclei of almost all acinar cells as well as to the majority of nuclei in ductal cells. Very few of the nuclei of connective tissue and endothelial cells stained positively. The presence of androgen receptors in human salivary glands suggests possible direct effects of androgens on these tissues. PMID- 8517802 TI - Effects of jaw clenching, jaw movement and static jaw position on facial skin sensitivity to non-painful electrical stimulation in man. AB - The effects of isometric jaw clenching, static jaw position and jaw movement on electrically evoked perception thresholds of the facial skin of the mental region were studied in healthy human subjects. Exercise consisted of brief (1 s) isometric contractions of jaw-closing muscles against a static load (30% of the maximum force), or continuous jaw movements at two different frequencies (1 and 3 Hz). A visual cue was used to indicate the start and end of the isometric exercise (duration 1 s.). Isometric jaw clenching induced a significant elevation of perception thresholds in the skin of the lower jaw just before and during the early electromyographic response of the jaw-closing muscles. This elevation was attenuated before the end of the exercise. Corresponding thresholds evoked by electrical stimulation applied to the dorsum of the hand were not changed by isometric jaw clenching. Changes in static jaw position did not have any effect on detection thresholds. Continuous 'masticatory-like' jaw movements produced a velocity-dependent reduction of sensitivity in the facial skin. The suppression was significantly stronger than that produced by isometric jaw exercise. An imagined isometric biting exercise, which presumably activated the supplementary motor cortex, did not cause any threshold elevations. The results indicate that isometric jaw clenching as well as cyclical jaw movements produce segmentally a phasic, rapidly attenuating masking of facial skin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517803 TI - Longitudinal evaluation of peripheral blood monocyte secretory function in periodontitis-resistant and periodontitis-susceptible patients. AB - The purpose of this investigation was to evaluate lipopolysaccharide (LPS) stimulated monocyte secretory responses longitudinally in patients with generalized severe chronic adult periodontitis (periodontitis-susceptible) and controls with gingivitis (periodontitis-resistant). In addition, the expression of constitutive (Leu-M3) and LPS-inducible (Mo3e) antigens on monocytes isolated from these two groups was examined. Monocyte secretory function was assessed longitudinally; the effect of periodontal therapy in the susceptible patients was examined by comparing monocyte function before and after their treatment. Peripheral blood monocytes were isolated by counterflow centrifugal elutriation and treated with control medium or media containing 1 microgram/ml of Salmonella typhimurium LPS or Prevotella intermedia LPS with or without human recombinant interferon (IFN)-gamma pretreatment. Prostaglandin E2, F2 alpha and thromboxane B2 were quantified in culture samples by gas chromatography-mass spectrometry (GC MS) and interleukin-1 beta was quantified by enzyme-linked immunosorbent assay. Leu-M3 and Mo3e antigen expression was assessed by FACScan. Three major findings were made. First, LPS-stimulated IL-1 beta release by monocytes from susceptible patients was depressed relative to that in resistant patients at the initial donation. After periodontal therapy, there was virtually identical IL-1 beta release in LPS-stimulated cultures from both groups. However, in susceptible patients IL-beta release was diminished after periodontal therapy in cultures pretreated with IFN-gamma. Second, there was a significant drift in monocyte secretion of prostaglandin E2 in samples from the resistant patients between the first two donations and the third donation. PGE2 release did not differ between groups at the initial donation, although there was a depression in PGE2 release in the susceptible group at the final donation when IFN-gamma was followed by S. typhimurium LPS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517804 TI - In vitro and in vivo evaluations of Chinese traditional (kampo) medicines as anticalculus agents in the rat. AB - Inhibitory effects of two Chinese traditional (Kampo) medicines, Shigyaku-san and Shikunshi-to, on the in vitro formation of calcium phosphate precipitates and the in vivo deposition of supragingival dental calculus were studied. Both had inhibitory effects on hydroxyapatite transformation and induction; effects of Shigyaku-san and Shikunshi-to were 1/100 and 1/400 of that of 1-hydroxyethylidene 1,1-bisphosphonate (HEBP). When used topically (in drinking water) for 4 weeks, 20-40 mg/ml of Shigyaku-san or Shikunshi-to reduced the formation of dental calculus by 40-60%, while 0.03% (w/v) HEBP decreased it by 70-98%. However, when these drugs were given by gastric intubation for 2 weeks, they were all ineffective, suggesting that the observed anticalculus effects were of topical rather than of systemic origin. PMID- 8517805 TI - Anterior tooth relations in Kenyan Africans. AB - Dental plaster casts of 235 Maasai, 116 Kikuyu and 61 Kalenjin children aged 3-16 yr were studied to determine the incidence and magnitude of diastemas, overbite, overjet and anterior open bite. The highest prevalence of diastema was amongst the Maasai (61.3%), of overbite (84%) and overjet (99%) amongst the Kikuyu, and of anterior open bite amongst Kalenjin (24%), with values greater than 0.4 mm up to 11.5 mm. Comparison of the mean values showed that diastema (1.77 mm) and overjet (4.4 mm) were greatest in Maasai, overbite (3.53 mm) in Kalenjin, and anterior open bite (3.50 mm) in Kikuyu. In the total sample, the prevalence and mean of diastema were 49%, 1.68 mm; of overbite 77.4%, 2.96 mm; of overjet 88.6%, 3.83 mm; and of anterior open bite 16.5%, 2.69 mm (with values between 0.4-11.5 mm), while 5.5% had an edge-to-edge bite (-0.5-0.5 mm). The prevalence of diastema decreased whilst its magnitude increased with age. The mean values of overbite and overjet increased, while those for anterior open bite decreased with age. The mean values of diastema, overbite and overjet were greater amongst the females, but the difference was significant only for overjet. The high prevalence and greater values of measurements of anterior tooth relations may be related to variable growth of the bimaxillary dentoalveolar complex and soft tissue influences. This may be important in orthodontic treatment planning, dental prostheses and other clinical dental treatments in Kenyan populations. PMID- 8517806 TI - Serial variation in histological character of articular soft tissue in young human adult temporomandibular joint condyles. AB - Histological variation was studied in serial sections, in contrast to previous studies which have generalized from representative sections. The sample consisted of consecutive serial sagittal sections from the central third of nine condyles, plus an accompanying stone cast showing the intact articular surface before sectioning. The thickness of the articular soft tissue and its fibrous connective tissue and cartilage components was measured, and the presence of undifferentiated mesenchymal (UM) cells was assessed by low-power light microscopy. Components of variance analysis showed that section-to-section variation in thickness was of the same order as differences between joints, each explaining approx. 50% of the variance in both connective tissue and cartilage thickness. The fibrous connective tissue contributed as much to the overall variation in soft tissue thickness as did the cartilage component (SD 0.0946 versus 0.0909 mm for the superior sector). Serial UM cell variability was common, and the UM cells were often distributed in islands rather than uniformly across the articular tissue. Condyles with the greatest surface irregularity were characterized by greater serial variability in fibrous connective tissue thickness, more frequent absence of cartilage, and more areas of UM cell depletion. These results suggest that serial variation in histological character may be more important than mean values in the description of surface contours and articular tissue relations in the temporomandibular joint. This should influence the design of future investigations. PMID- 8517807 TI - The possible influence of the menstrual cycle on the adherence of Candida albicans to human buccal epithelial cells in vitro. AB - Although the influence of the menstrual cycle on both vaginal candidosis and Candida albicans adherence to vaginal epithelial cells in vitro has been shown to be significant, similar studies have not been made on oral candidosis and adherence to buccal epithelial cells. The aim of this study was therefore to use an in vitro adherence assay to investigate the possible influence of the menstrual cycle on the adherence of C. albicans to buccal epithelial cells. Epithelial cells were collected from a single, healthy, female volunteer on days 5, 15, 22 and 28 of six menstrual cycles. Adherence of C. albicans was significantly higher to buccal epithelial cells collected on day 5 of the menstrual cycle when compared with days 15, 22 and 28, both in terms of the percentage of buccal epithelial cells with adherent C. albicans and the number of C. albicans adhering per 200 buccal epithelial cells in four out of six menstrual cycles (p < 0.001). This result indicates that hormonal influences should be considered when buccal epithelial cells are used in vitro to assess candidal adherence and may implicate hormonal factors in the aetiology of oral candidosis. PMID- 8517808 TI - Immunohistochemical localization of cathepsins B and D in the synovial lining cells of the normal rat temporomandibular joint. AB - In 1 micron-thick serial cryosections, cathepsins B and D were found to coexist in both type A (macrophage-like) and type B (fibroblast-like) cells: the whole cytoplasm of the type A cells showed strong immunoreactivity, while the type B cells contained a few granular reaction products. It is therefore suggested that type A cells have a marked ability for intracellular digestion of organic materials. PMID- 8517809 TI - Managing hypertension. PMID- 8517810 TI - Multiple risk factor assessment in the management of hypertension. AB - Hypertension is only one factor in the ultimate risk of developing cardiovascular or cerebrovascular disease. An outline of the relative importance of other factors, and the expected benefits from their modification is presented. PMID- 8517811 TI - The importance of measuring sodium and potassium excretion. AB - Non drug treatment of hypertension is being given increasing attention. In this article the role of salt restriction is evaluated. PMID- 8517812 TI - High blood pressure--current state of play. AB - Blood pressure is well recognised and well treated in Australia; nevertheless, a number of problem areas still exist. The author looks at the management of hypertension in the elderly, factors affecting choice of drug and the place of cost-benefit analysis in choosing a drug for treatment of hypertension. PMID- 8517813 TI - Does war stress contribute to hypertension? AB - Veterans often apply to the Department of Veterans' Affairs to have their hypertension accepted as related to their war service. Claims may be rejected on the grounds that stress does not affect hypertension. Veterans' organisations often recommend an appeal and general practitioners may then become involved. This article was written to help the practitioner advise the veteran and explains why hypertension may be granted on appeal. PMID- 8517814 TI - Hypertension: are we getting the message? AB - Hypertension remains the commonest condition requiring ongoing medical treatment in general practice and yet treatment and follow up still pose major difficulties. The author explores the reasons for these difficulties and suggests ways to overcome them. PMID- 8517815 TI - The uncertainties of clinical practice. AB - 'Science and technology have successfully removed uncertainty from diagnosis and management in clinical practice' is the essay topic required of candidates for the Post Graduate Diploma in Family Medicine at Monash University, Melbourne. Bruce Alcorn, a general practitioner from Kangaroo Island, South Australia, provides a thought provoking treatise on this subject. PMID- 8517816 TI - Lichen sclerosus, genital trauma and child sexual abuse. AB - OBJECTIVE: To describe the clinical features of lichen sclerosus affecting the genitalia of three unrelated prepubertal girls in whom concerns of sexual abuse had been raised. CLINICAL FEATURES: three girls ranging from 4 to 9 years of age presented with similar genital and anal findings. Their labial skin was atrophic with pale opalescent patches and a variable amount of labial bruising, haemorrhagic blistering and bleeding. In two, the perianal skin was involved in a similar fashion. In each case the hymen was normal with no sign of acute or chronic trauma. CONCLUSIONS: Lichen sclerosus affecting the genitalia of prepubertal females is an uncommon condition that may be mistaken for trauma associated with sexual abuse. An awareness of its clinical features is essential not only for those doctors who examine children for physical signs of sexual abuse but also for primary care doctors who may be confronted with an apparently abused child. Early recognition of this disease should, in the absence of other concerns, prevent unnecessary intervention by police and child protection workers. PMID- 8517817 TI - Asthma in general practice. Opportunities for recognition and management. AB - OBJECTIVE: To describe the prevalence of asthma-related symptoms and asthma among patients attending general practitioners. SETTING: Sydney. DESIGN: Cross sectional survey by written questionnaire. SAMPLE: 1933 patients of 21 general practitioners. RESULTS: 1. Wheeze and asthma were common in patients attending general practitioners; 19 per cent of patients reported recent wheeze, 9 per cent reported recent asthma. 2. Less than half of all patients with recent wheeze (47%) reported having asthma. 3. Recent wheeze without asthma was more common in boys (4.8%) than girls (0%) and more common in men (10%) than women (7%). 4. Although most patients reporting asthma (95%) had had their asthma treated by a doctor, three-quarters of those patients had experienced asthma related symptoms in the previous year. CONCLUSION: Asthma remains under-recognised and under treated among patients attending general practitioners. PMID- 8517818 TI - Use of the sleep diary in the management of patients with insomnia. AB - A sleep diary can be used to monitor the frequency and dosage of hypnotic drug use, to indicate to patients the quality of their sleep and the changes in quality with and without medication, and to help elderly patients understand the nature of their insomnia and the impact of day-time sleeps on their night-time sleep pattern. It should be regularly used as part of the procedure for the diagnosis and management of patients presenting with insomnia. Used in this way it benefits both the patient and the doctor. PMID- 8517819 TI - Pulmonary sarcoidosis and chronic cutaneous atypical mycobacter ulcer. AB - This interesting case of pulmonary sarcoidosis and Mycobacterium ulcerans ulcers raises many issues: 1. Our paucity of knowledge of deficient immune status in individuals; the multifarious presentation as recognisable ill health, its early detection, treatment and its prevention. In this present case the management of the immune status of the patient has not yet been fully addressed. The relationship between his pulmonary sarcoidosis as being an 'immune' response to the Mycobacterium ulcerans remains speculative; for example, did this patient have the Mycobacterium infection before he was diagnosed as having sarcoidosis? There is no evidence of this. With the history of repeated cellulitis associated with his business trips to Asia and the Middle East, the likelihood seems speculative--as would infection with Mycobacterium ulcerans contracted from swimming in pools and rivers. 2. As sarcoidosis is thought to have an association with Mycobacterium tuberculosis it is tempting to suggest that as, in this case, the Mycobacterium ulcerans is the caus-ative agent for his sarcoidosis. Additionally, should we be looking for sarcoidosis in every other case of Mycobacterium ulcerans infection? Other cases of Mycobacterium ulcerans could be assessed. 3. It is suggested that corticosteroids do pave the way for opportunistic infection as in this case. How often does this occur in 'usual practice' where patients are exposed to corticosteroids? Further comments are invited. 4. The question of sterility techniques in the home (daily dressings), the surgery, and at work as a food handler, is noted as a matter of concern. 5. The implications of the problem having any work-related association is also noted in passing. PMID- 8517820 TI - A practical approach to the management of heart failure. AB - The pathophysiology of the serious and disabling problem of heart failure has been confirmed to involve activation of multiple neuroendocrine systems, especially the sympathetic system and renin angiotensin aldosterone system. The results of several large scale clinical trials demonstrate that reduction in morbidity and mortality are possible with currently available drugs. The benefits for the patient can be maximised by early intervention, especially by the family physician as opposed to interventions applied late, which often yield minimal benefit. PMID- 8517821 TI - Recruiting general practitioners for survey research. AB - Recruitment is often a lengthy process and sometimes a frustrating one. It is not simply a matter of contacting those selected and asking for this participation. After obtaining a list from which to select a sample, a contact list must be created, initial contact must be made and direct contact initiated, often requiring great powers of persuasion. It is often difficult to convince someone that your project is important. However, the time and energy expended is ultimately worth it. Just one positive enthusiastic response is enough to make you forget all the difficulties. What could be done to make it simpler in the future? Some kind of list, regularly updated, of all general practitioners would make researchers' jobs much easier by providing a reliable and current sampling frame. It would also promote general practice as a specialty. The problem of a definition of general practice is currently being considered. Overall, there needs to be more recognition of the time practitioners put in to such surveys and the additional demands it places on their already busy lives. General practice research has to be designed to fit into the practitioner's schedule. Researchers should co-ordinate their projects so that repeated requests are not made to the same practitioner. To some extent this problem is being tackled in New South Wales at present by the Royal Australian College of General Practitioners and University researchers. There is also a need for feedback from participating practitioners as to their own thoughts about the direction and design of general practice research. This would help to encourage continued participation and create goodwill for future surveys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517822 TI - Dr Margaret Hollands. Part of a medical team. AB - Country practice is certainly not for the faint hearted, but by embracing all that it has to offer a full and rewarding life is possible. "One of the most satisfying things that I have found is delivering the babies of girls whom I also delivered and being so closely involved in family sagas. Often I write down the stories of the day's consultations and they are better than any fiction. Maybe one day it will get into print." PMID- 8517823 TI - Patient education. Vasectomy. PMID- 8517824 TI - "My head is bursting, doctor.". PMID- 8517825 TI - Scholarship and fellowship awards. PMID- 8517826 TI - Variations on a theme. AB - Three stories--death, disaster, demineralisation--a typical mixture in our daily lives. In the musical world, theme and variation require the musician to choose a piece of music and write in and around it. Thus, for example, the well known Rachmaninov's Variations on a theme by Paganini. In the general practice would our themes start with an incident or happening--its the patients that bring about the variations. What interesting variations we see. PMID- 8517827 TI - Recipe for a writ. Poor rapport+unmet expectation+big bill = a writ. PMID- 8517828 TI - 'Frank'. A case of occupational respiratory distress. AB - This case presents a protracted and difficult problem of occupational lung disease. My role as general practitioner involved sifting through several expert opinions and balancing sometimes conflicting requirements of the employer to determine the best management programme for the patient's well-being; day-to-day counselling, and an advocacy role for the patient. The rarity of the final diagnosis, and confounding emotional factors meant that appropriate management was frequently difficult to determine. PMID- 8517829 TI - Extemporaneous prescribing. Module 2. AB - Australian Family Physician is pleased to present a home course in extemporaneous prescribing, an interesting area that is poorly understood by many practitioners, especially recent graduates. Dr Bernard Kelly has been teaching this discipline to Family Medicine Trainees in New South Wales for many years and has written a series of modules to be placed in the journal during 1993. A question is included at the end of each module. PMID- 8517830 TI - Treatment of plaques of psoriasis. PMID- 8517831 TI - Tissue adhesives. PMID- 8517832 TI - GPs and solicitors. PMID- 8517834 TI - Postgraduate training for GPs. PMID- 8517833 TI - Health promotion for older people. PMID- 8517835 TI - Mini mental state examination. PMID- 8517836 TI - Better guidelines to rheumatoid arthritis therapy. PMID- 8517837 TI - Campaigning for health. PMID- 8517838 TI - Thrombosis and antiphospholipid antibodies--an evolving story. PMID- 8517839 TI - Clinical analysis of 125 patients with the lupus anticoagulant. AB - A retrospective analysis of 125 consecutive lupus anticoagulant (LA) positive patients and 125 age, sex matched lupus anticoagulant negative controls is reported with the aims of defining further the clinical spectrum of disease, determining at-risk subgroups and management strategies. There was no significant difference in the incidence or pattern of complications in those with systemic lupus erythematosus (SLE) and related disorders, and those without SLE. Venous thromboembolism, immune thrombocytopenia, foetal loss, depression and hypertension were statistically more common in the LA group than in the control group. In contrast to previous reports, children aged ten years or less with the LA developed significantly more complications than controls. Patients with the LA secondary to drugs also developed complications, a finding which is also at variance with previous reports. There was a significant difference in the outcome of arterial disease (p < 0.04) and venous thromboembolism (p < 0.001) when long term anticoagulation was part of the treatment regimen. PMID- 8517840 TI - Impact of a national educational campaign to reduce patient delay in possible heart attack. AB - In 1989 the National Heart Foundation (NHF) of Australia's Heart Week campaign was directed towards encouraging those with symptoms of possible myocardial infarction (MI) to seek help as promptly as possible. To evaluate its effect, three surveys were conducted of patients admitted to 22 coronary care units (CCUs). Two (335 and 221 patients) preceded and one (253 patients) followed the public education campaign. During the third survey a subset of patients were asked why they delayed, how long they thought one should wait before seeking help, whether they were aware of the media campaign and whether this had influenced their behaviour. Overall, only 42% of 809 patients sought help within one hour (median delay 1.2 hours). The median time of arrival and the proportion of patients arriving within one, two and four hours was not altered after this campaign. Those who admitted to having been aware of the campaign sought help no more promptly. The Heart Week campaign could not be shown to have produced any clinically important change in patient delay. Future campaigns will need to be modified in the light of this experience. PMID- 8517841 TI - Lipid, lipoprotein and apolipoprotein distributions in an elderly New Zealand population. AB - The aim of this study was to determine the lipid, lipoprotein and apolipoprotein distribution in an ambulant elderly New Zealand population, and to consider the association between these and other variables (including body mass index, diabetes mellitus, and smoking history) with the prevalence of manifest macrovascular disease in a cross-section analysis. The population sample was randomly selected from the age/sex register of a large urban medical centre in Christchurch, New Zealand. A total of 369 subjects (participation rate 69%) aged 65 years and older were screened for manifest macrovascular disease, diabetes mellitus, smoking status, height and body weight. Levels of plasma total cholesterol, triglycerides, HDL cholesterol, apolipoproteins AI and B, glucose, glycated haemoglobin and fibrinogen were measured. Three way analysis of variance (ANOVA) was used to compare continuous variables across age/sex/macrovascular disease groups. Females had significantly higher levels of total and HDL cholesterol, apolipoproteins AI and B than males. Body mass index showed a significant decrease with increasing age. Macrovascular disease was manifest in 24% of males, and in 26% of females. No direct correlation was seen between any of the measured continuous variables and the presence of macrovascular disease, except for fibrinogen (P < 0.05). No significant association was seen between macrovascular disease and smoking status, nor with a diagnosis of diabetes. In females, the frequency of macrovascular disease was significantly higher amongst those with low (< 1.00 mmol/L) levels of HDL. PMID- 8517842 TI - Wegener's granulomatosis: clinical features and prognosis in 37 patients. AB - Thirty-seven patients (21 female, 16 male) with Wegener's granulomatosis (WG) were reviewed. Patients were followed for a mean six years after diagnosis; 14 were followed for more than seven years. The clinical features were similar to those in previous studies. In this series, only 13 patients (35%) had renal disease at presentation and the cumulative incidence of renal involvement was 51%. Thirty-one patients received treatment which included cyclophosphamide (CP). The case fatality rate of the six patients not treated with CP was 83% (five deaths). By contrast, all CP treated patients improved and 21 (68%) had complete remissions. Nine (29%) were in complete remission for a mean 4.9 years after discontinuing all treatment. Two were disease free for over ten years. The actuarial probability of survival for these patients was 97% at one year and 71% at ten years. Only three CP treated patients (10%) progressed to end-stage renal disease. The case fatality rate was 26% (eight patients) and sepsis was the cause of death in five. Fourteen patients (45%) treated with CP had at least one relapse of vasculitis and seven (23%) had multiple (two or more) relapses. These data indicate that CP is effective in inducing remissions and prolonging survival in patients with WG; however, relapses are frequent. PMID- 8517843 TI - Kennedy's disease: genetic diagnosis of an inherited form of motor neuron disease. AB - Kennedy's disease (X-linked spinal and bulbar muscular atrophy) is an inherited form of motor neuron disease that may be diagnosed genetically using the polymerase chain reaction (PCR). This form of motor neuron disease principally affects the proximal limb girdle muscles as well as those involved with deglutition and phonation. Onset is usually late, in the fourth to fifth decades of life, and progression is slow. Moderate gynaecomastia and testicular atrophy are usually present, suggesting a defect in androgen receptor function. Being inherited in an X-linked recessive manner, only males are affected, with females as the unaffected carriers. The genetic abnormality that causes Kennedy's disease is an enlargement of the androgen receptor (AR) gene, which is located on the proximal long arm of the X chromosome. In patients with this disease, a region in the gene containing repeated CAG triplet nucleotides is approximately twice the size of that found in normal people. Using PCR to amplify this region of the AR gene, this study confirms this genetic mutation in 12 males from eight different families. All these families live on the east coast of Australia. This mutation was not found in five patients with other forms of motor neuron disease. Twelve heterozygote females, the daughters of affected males and carrier females, have also been identified. In addition, there are 14 asymptomatic and as yet untested sons of carriers, ranging in age from less than one year to over 40 years of age. Each has a 50% chance of inheriting the abnormal gene from his mother and thus developing Kennedy's disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517844 TI - The use of suppressive agents for the treatment of rheumatoid arthritis. PMID- 8517845 TI - Role of T-cell antigen receptors in rheumatic disease. AB - The initiation and perpetuation of many rheumatic diseases is believed to be mediated by specific T-cells activated by an unknown antigenic peptide present on the surface of antigen presenting cells (APC). The T-cell antigen receptor (TCR) plays a central role in the recognition of antigen and subsequent T-cell activation. It is thought that a selective TCR repertoire may contribute to the immunopathogenesis of certain inflammatory rheumatic diseases. In this review recent progress in our understanding of TCR usage and their role in a variety of rheumatic diseases will be discussed. In addition, novel immunotherapeutic strategies based on a better understanding of the molecular mechanisms of antigen recognition will be reviewed. PMID- 8517846 TI - Thrombolysis for presumed myocardial infarction--pitfalls in diagnosis. PMID- 8517847 TI - Hypoplastic crisis with persistent arthralgia and prolonged parvovirus B19 viraemia detected by polymerase chain reaction. PMID- 8517848 TI - Another parvovirus B19 infection of a chronic lymphatic leukaemia patient. PMID- 8517849 TI - Stroke complicating severe ovarian hyperstimulation syndrome. PMID- 8517850 TI - Severe systemic vasculitic syndrome post influenza vaccination. PMID- 8517851 TI - Mechanisms of neural crest cell migration. AB - Neural crest cells are remarkable in their extensive and stereotypic patterns of migration. The pathways of neural crest migration have been documented by cell marking techniques, including interspecific neural tube grafts, immunocytochemistry and DiI-labelling. In the trunk, neural crest cells migrate dorsally under the skin or ventrally through the somites, where they move in a segmental fashion through the rostral half of each sclerotome. The segmental migration of neural crest cells appears to be prescribed by the somites, perhaps by an inhibitory cue from the caudal half. Within the rostral sclerotome, neural crest cells fill the available space except for a region around the notochord, suggesting the notochord may inhibit neural crest cells in its vicinity. In the cranial region, antibody perturbation experiments suggest that multiple cell matrix interactions are required for proper in vivo migration of neural crest cells. Neural crest cells utilize integrin receptors to bind to a number of extracellular matrix molecules. Substrate selective inhibition of neural crest cell attachment in vitro by integrin antibodies and antisense oligonucleotides has demonstrated that they possess at least three integrins, one being an alpha 1 beta 1 integrin which functions in the absence of divalent cations. Thus, neural crest cells utilize complex sets of interactions which may differ at different axial levels. PMID- 8517852 TI - Protein trafficking along the exocytotic pathway. AB - Proteins of the exocytotic (secretory) pathway are initially targeted to the endoplasmic reticulum (ER) and then translocated across and/or inserted into the membrane of the ER. During their anterograde transport with the bulk of the membrane flow along the exocytotic pathway, some proteins are selectively retained in various intracellular compartments, while others are sorted to different branches of the pathway. The signals or structural motifs that are involved in these selective targeting processes are being revealed and investigations into the mechanistic nature of these processes are actively underway. PMID- 8517853 TI - Gene expression during metamorphosis: an ideal model for post-embryonic development. AB - The precocious induction in vivo and in culture of insect and amphibian metamorphosis by exogenous ecdysteroids and thyroid hormones, and its retardation or inhibition by juvenile hormone and prolactin, respectively, has allowed the analysis of such diverse processes of post-embryonic development as morphogenesis, tissue remodelling, functional reorganization, and programmed cell death. Metamorphosis in vertebrates also shares many similarities with mammalian development in the late foetal and perinatal period. This review describes the regulation of expression of some of the 'adult' gene products during metamorphosis in invertebrates and vertebrates. Recent studies on metamorphosis have revealed the important role played by auto-induction of hormone receptor genes, based on which a model will be presented to explain the activation of 'downstream' genes which give rise to the adult phenotype. It will also be argued that metamorphosis is an ideal model for analyzing some of the major mechanisms governing post-embryonic development. PMID- 8517854 TI - Genes controlling nucleotide excision repair in eukaryotic cells. AB - The maintenance of genetic integrity is of vital importance to all living organisms. However, DNA--the carrier of genetic information--is continuously subject to damage induced by numerous agents from the environment and endogenous cellular metabolites. To prevent the deleterious consequences of DNA injury, an intricate network of repair systems has evolved. The biological impact of these repair mechanisms is illustrated by a number of genetic diseases that are characterized by a defect in one of the repair machineries and in general predispose individuals to cancer. This article intends to review our current understanding of the complex nucleotide excision repair pathway, a universal repair system with a broad lesion specificity. Emphasis will be on the recent advances in the genetic analysis of this process in mammalian cells. PMID- 8517855 TI - Early human embryo metabolism. AB - Non-invasive microanalytical methods have been devised to study the energy metabolism of single human preimplantation embryos. Pyruvate, which is added routinely to all media used to culture human embryos, is consumed throughout the preimplantation period, with glucose assuming an increasing role at embryo compaction and blastocyst formation. All of the glucose consumed may be accounted for by the appearance of lactate in the incubation medium. The enzyme hexokinase may be involved in regulating this aerobic glycolysis. There is considerable indirect evidence for the utilisation of endogenous as opposed to exogenous energy substrates, the most likely candidate being protein. Information on early human embryo metabolism is likely to find application in a number of areas: these include the improvement of techniques for assisted human conception, notably in the selection of embryos for transfer following In Vitro Fertilisation; the diagnosis of genetic defects at the preimplantation stage; increased understanding of the causes of implantation failure and miscarriage, and the development of novel post-coital contraceptives. PMID- 8517856 TI - Mutation of N-myc in mice: what does the phenotype tell us? AB - Oncogenesis is manifested as uncontrolled cellular proliferation and in some situations a failure of normal differentiation in the transformed cell. This has led to speculation that the normal role of proto-oncogenes during development may be to mediate the relationship between proliferation and differentiation. The advent of gene targeting in ES cells allows the role oncogenes in development to be tested directly. Two recent studies have examined the phenotype of N-myc mutant mice generated by gene targeting. In both reports, the mutation is an embryonic lethal at 11.5 days of gestation confirming a critical role for this proto-oncogene in development and the inability of other members of the myc family to substitute functionally for N-myc. Although the phenotypes are similar in general outline, the two reports differ in the specifics of the morphological and histological abnormalities identified. The disparity may result from the mutation created, the genetic background of the mutant mice or the criteria used to determine abnormalities. Assuredly, there is valuable information to be gained about N-myc function from these mutant mice. However, these reports make it clear that morphological and histological abnormalities in N-myc mutant mice serve as a starting point rather than as an endpoint. The challenge now is to link the defect at the cellular level to the abnormalities at the physiological level. PMID- 8517857 TI - Bacteriophage lambda: transactivation, positive control and other odd findings. PMID- 8517858 TI - Dimethylamine formation in man. AB - Trimethylamine N-oxide, a common food component, has been identified as a major source of urinary dimethylamine in man. The potential pathophysiological consequences of exposure to dietary derived dimethylamine are raised. PMID- 8517859 TI - Kinetics of the inhibition of tumour growth in mice by eicosapentaenoic acid reversal by linoleic acid. AB - Oral administration of eicosapentaenoic acid (EPA) (2.0 g/kg) by gavage to female NMRI mice bearing the MAC16 colon adenocarcinoma and with weight loss, prevented further loss in body weight and produced a delay in the growth of the tumour. Cell production and loss were determined by the [125I]5-iodo-2'-deoxyuridine method during the stationary and growth phase of the tumour in animals treated with EPA. Tumour stasis appeared to arise from an increase in the rate of cell loss from 38 to 71% without a significant change in the potential doubling time. During the subsequent growth phase the cell loss factor was reduced to 52% and this was combined with a reduced potential doubling time from 32 to 26 hr. The antiproliferative, but not the anticachectic effect of EPA could be reversed by oral administration of pure linoleic acid (LA), (1.9 g/kg) which acted to increase tumour growth by reducing the cell loss factor to 45%. Despite this reversal, incorporation of EPA into tumour cell lipids was not significantly different in animals administered with either EPA alone or combined with LA. This suggests that the antiproliferative effect of EPA in this system may arise from an indirect effect through the blocking of the catabolic effect of the tumour on host adipose tissue, which normally supplies fatty acids essential for tumour growth. This suggests that LA may be required by some tumours to prevent cell loss and that the catabolism of adipose tissue, which accompanies cancer cachexia effectively supplies this fatty acid to the tumour. PMID- 8517860 TI - The role of alpha-tocopherol as a peroxyl radical scavenger in human low density lipoprotein. AB - It is thought that the oxidation of low density lipoprotein (LDL) plays a key role in the pathogenesis of atherosclerosis. It is well known that lipid peroxidation reactions are propagated by peroxyl radicals and it follows, therefore, that the capacity of an individual LDL particle to scavenge these oxidants may be an important indicator of its atherogenic potential. There are several components within LDL which scavenge peroxyl radicals including chain breaking antioxidants and amino acids on the protein. It is not clear at present which of these antioxidants is most important. In attempting to address the question we have used a simple method for the measurement of the total capacity of the LDL particle to scavenge peroxyl radicals. This assay depends upon the ability of antioxidants in LDL to inhibit the peroxyl radical dependent oxidation of luminol. We have found that approximately 80% of the antioxidant capacity of LDL, isolated from a number of donors, could be accounted for by the alpha tocopherol present in the samples. We have compared these results with those obtained when the identical samples of LDL were oxidized with copper and found, as reported by others, a wide range in the susceptibility of the different LDL preparations to oxidation by this transition metal. We suggest that this variability is unlikely to be due to differences in the ability of an LDL particle to scavenge peroxyl radicals. PMID- 8517861 TI - Pravastatin inhibited the cholesterol synthesis in human hepatoma cell line Hep G2 less than simvastatin and lovastatin, which is reflected in the upregulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and squalene synthase. AB - The possible difference between lovastatin (mevinolin, MK-803), simvastatin (MK 733) and pravastatin (CS-514), all chemically-related competitive inhibitors of 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, were tested in the human hepatoma cell line Hep G2, which is often used as a model for the human hepatocyte. After an 18-hr incubation of the cells with the drugs, pravastatin (IC50 = 1900 nM) was less potent than simvastatin and lovastatin (IC50 = 34 and 24 nM, respectively) in inhibiting the sterol synthesis. As a consequence of this inhibition, the HMG-CoA reductase mRNA levels and squalene synthase activity, both negatively-regulated by sterols, were increased equally by simvastatin and lovastatin, whereas the induction by pravastatin was much less. In contrast, there were fewer differences between the compounds in inhibiting HMG-CoA reductase activity, when assayed directly in Hep G2 cell homogenates (IC50 values = 18, 61 and 95 nM for simvastatin, lovastatin and pravastatin, respectively). Moreover, in experiments with human hepatocytes in primary culture the IC50 values for inhibition of the cholesterol synthesis by simvastatin and pravastatin were of the same order of magnitude (23 and 105 nM, respectively). The results are therefore explained as follows: the three drugs act in the same way within the Hep G2 cell in terms of inhibiting HMG-CoA reductase and their subsequent effect on the feedback regulation of the cholesterol synthesis, i.e. increasing squalene synthase and HMG-CoA reductase mRNA. However, pravastatin seems to be less able to enter the cells compared with simvastatin and lovastatin, possibly because of the higher hydrophobicity of the latter compounds. The observation with human hepatocytes suggests that in Hep G2 cells a specific hepatic transporter is missing. On one hand the human hepatoma cell line Hep G2 has proved to be a good model for the study of the feedback regulation of enzymes of the cholesterol biosynthetic pathway such as HMG-CoA reductase and squalene synthase, but, on the other hand seems to be less suitable as a model for the study of specific uptake of drugs, e.g. the vastatins, in human hepatocytes. PMID- 8517862 TI - Role of mitochondria in cisplatin-induced oxidative damage exhibited by rat renal cortical slices. AB - The role of mitochondria with regard to cisplatin-induced renal toxicity has been examined in vitro. The mitochondria were prepared from rat renal cortical slices which had been exposed to cisplatin. Incubation of the kidney slices with 2 mM cisplatin for various periods depleted glutathione (GSH) and increased thiobarbituric acid reactive substances (TBARS) in a time-dependent manner, a change which indicates lipid peroxidation in the mitochondria. The content of GSH was significantly depleted within 15 min of incubation, while TBARS formation was increased after 60 min of incubation. Marked depletion (30%) of GSH and increased TBARS formation (2-fold) were observed after 60 min and 120 min of incubation, respectively. Furthermore, cisplatin also depleted GSH and induced TBARS formation in the mitochondria in a concentration-dependent fashion. Cisplatin (0.5 mM) depleted GSH, but did not increase the production of TBARS. In addition, the fluorescence intensity of 8-anilino-1-naphthalenesulphonic acid (ANS)-bound to mitochondrial membranes was decreased after 120 min of incubation with 2 mM cisplatin. Several parameters were measured as indicators of damage to mitochondria and cellular integrity and they showed that cytotoxicity occurred subsequent to both GSH depletion and TBARS formation. Cisplatin-induced depletion of GSH is an early event and a determinant step in oxidative stress to mitochondria in the kidney cortex and may lead to irreversible cell injury. PMID- 8517863 TI - The effect of side chain substitution at positions 2 and 3 of the heterocyclic ring of N-acetylenic analogues of tryptamine as monoamine oxidase inhibitors. AB - N-Acetylenic analogues of tryptamine in which the side chain is located at position 2 of the indole ring are compared with those in which the side chain is located at position 3, in terms of their actions as inhibitors of monoamine oxidases A and B. IC50 values at 0 and 30 min of pre-incubation were determined. Time-dependence and irreversible inhibition confirmed that all of them behave as mechanism-based inhibitors. The kinetic constants of each inhibition step were determined for both monoamine oxidase forms and compared between them. In all cases the first-order rate constants for the covalent adduct formation were similar to inhibitor selectivity which is derived solely from differences in affinities for non-covalent binding to the A and B enzymes. Those compounds where the acetylenic side chain was substituted at position 2 of the heterocyclic ring and selective inhibitors of monoamine oxidase A were more potent than those with the side chain in position 3. PMID- 8517864 TI - Formation of ligand and metabolite complexes as a means for selective quantitation of cytochrome P450 isozymes. AB - The suitability of triacetyloleandomycin (TAO) metabolite complex formation and metyrapone binding to reduced cytochrome P450 as a means for selective isozyme quantitation has been studied. Although isozymes of both subfamilies bind metyrapone in the reduced state, selective quantitation of 2B isozymes through the metyrapone complex is possible after complex formation of P450 3A with a TAO metabolite. Thus, consecutive application of both reactions allows the spectroscopic quantitation of P450 3A and 2B isozymes. Complete conversion of P450 3A into the complex, a precondition for P450 3A quantitation, requires NADH in addition to NADPH. A precise collective quantitation of 3A + 2B isozymes as metyrapone complexes alone is not possible because the corresponding complexes possess different molar extinction coefficients, i.e 71.5 and 52 mM-1 cm-1 at 446 490 nm, respectively. The formation of the TAO complex appears to be quite specific, since it correlates well with 3A-specific enzymatic activities, i.e. TAO N-demethylation and formation of 2 beta-hydroxy-, 15 beta-hydroxy- and 6 dehydrotestosterone. P450 3A levels in liver microsomes of male rats either untreated or treated with TAO, dexamethasone (DEX), phenobarbital or hexachlorobenzene amount to 13%, 78%, 66%, 24% and 11% of total P450, respectively. Good correlation between these values and P450 3A-specific enzymatic activities is obtained. By the spectroscopic method, P450 2B isozymes could not be detected in microsomes of untreated rats. With TAO, DEX and hexachlorobenzene the microsomal 2B level is elevated to about 20% of total P450, i.e. to 0.8, 0.4 and 0.4 nmol P450/mg protein, respectively. 2B levels of about 60% of total P450 (0.75 nmol P450/mg protein) are obtained by phenobarbital treatment. Immunoblotting with anti-P450 2B shows that the ratio of expressed 2B1 and 2B2 differs depending on the type of inducer. DEX predominantly leads to induction of 2B2, which may explain the low pentoxyresorufin O-depentylase activity in these microsomes. PMID- 8517865 TI - Development and characterization of hydrogen peroxide-resistant Chinese hamster ovary cell variants--I. Relationship between catalase activity and the induction/stability of the oxidant-resistant phenotype. AB - Hydrogen peroxide (H2O2)-resistant sublines of Chinese hamster ovary (CHO) cells were isolated by in vitro exposure to the oxidant (treatment for 1 hr followed by 3 days of growth in peroxide-free medium). Stepwise increase in low level H2O2 concentrations produced variants which were progressively more resistant to the growth inhibitory effect elicited by the oxidant. Removal from H2O2 decreased resistance and the curve describing this process was biphasic in nature. In addition, the rate of loss of the H2O2-resistant phenotype was more rapid for the toxicity elicited by low concentrations of hydrogen peroxide, compared to that produced by high concentrations. Changes in total cell proteins were found to parallel the variations in sensitivity to the oxidant, since the protein content constantly increased during the adaptation process and decreases upon removal from H2O2. Catalase activity did not show large variations in resistant sublines with respect to the parental cell line, and these changes were at least partially related to differences in cell size/amount of total cell proteins of the sublines. In addition, the minor changes observed for catalase activity did not correlate with the degree of resistance to growth inhibition elicited by the oxidant. It may therefore be suggested that the H2O2-resistant phenotype of mammalian cells, initially adapted to low--then gradually increased- concentrations of the oxidant, is the result of a complex phenomenon which only partially involves over-expression of catalase. PMID- 8517866 TI - The relationship between intracellular Ca2+ and the mitochondrial membrane potential in isolated proximal tubular cells from rat kidney exposed to the nephrotoxin 1,2-dichlorovinyl-cysteine. AB - The effects of 1,2-dichlorovinyl-cysteine (DCVC) on the intracellular free calcium concentration ([Ca2+]i) and the mitochondrial membrane potential (delta phi) were investigated in freshly isolated rat kidney proximal tubular cells (PTC). Prior to cell death, DCVC induced a rise in [Ca2+]i and a decrease in the delta phi. Omission of extracellular calcium still resulted in a DCVC-induced increase of [Ca2+]i, indicating that calcium was released from intracellular stores. The beta-lyase inhibitor amino-oxyacetic acid completely protected against mitochondrial damage and cell death, indicating that the DCVC effects are dependent on beta-lyase metabolism. Incubation of the PTC with DCVC together with the intracellular-calcium complexing agents EDTA/acetoxy-methyl (AM), EGTA/AM or Quin-2/AM delayed (but did not prevent) the decrease of the delta phi and cell death, which indicates a relationship between [Ca2+]i and the decrease of delta phi. In individual cells four different responses induced by DCVC were observed; an increase of [Ca2+]i without an effect on delta phi, a decrease of delta phi and an increase of [Ca2+]i occurring simultaneously; an increase of [Ca2+]i preceded by a decrease of delta phi and a decrease of delta phi without any increase of [Ca2+]i. This indicates that DCVC-induced effects on [Ca2+]i and delta phi can appear independently. The data show that mitochondrial damage is potentiated by an elevation of [Ca2+]i, thereby creating a situation which rapidly leads to cell death. PMID- 8517867 TI - Differential effects of human recombinant interleukin-1 beta and dexamethasone on hepatic drug-metabolizing enzymes in male and female rats. AB - Interleukin-1 beta (IL-1) is one of the major inflammation mediators, commonly reported to be an inhibitor of hepatic drug metabolism. We studied the effect of IL-1 treatment on various drug-metabolizing enzymes in male and female rats. IL-1 induced both cytochrome P450 (P450) 3A1 activity and protein in females, but in males, IL-1 repressed P450 3A2 activity, without decreasing the protein. P450 1A1 was impaired in males, but was retained after dexamethasone pretreatment. IL-1 did not change P450 2B1/2 activity and protein, but counteracted their induction by dexamethasone. Uridine diphospho-glucuronosyltransferase (UGT) 1A2 (bilirubin) activity and its induction by dexamethasone were not affected by IL-1 treatment. Both P450 2C11 and epoxide hydrolase activities were repressed by IL-1 treatment, and both activities were impaired after dexamethasone treatment. These results clearly demonstrate that IL-1 acts at different steps of protein synthesis and gene expression. The effect of IL-1 on P450 was isoform-dependent, indicating that IL-1 can act on pretranscriptional events. The discrepancy between the variations of the activities and the protein of P450 3A2 suggests a post translational regulation. For P450 2C11, 3A1, and for microsomal epoxide hydrolase, but not for P450 1A1 and 2B1/2, IL-1 mimics the glucocorticoid effects. These differential effects can affect the kinetics and the bioavailability of drugs used in pathologies in which IL-1 is increased. PMID- 8517868 TI - Studies of cholecystokinin in the rat bed nucleus of stria terminalis. AB - The release of cholecystokinin from the dorsal and ventral region of the rat bed nucleus of stria terminalis was studied. Minislices from both regions were superfused with Krebs-Ringer-phosphate, and the cholecystokinin released into the physiological medium was concentrated previous to radioimmunoassay determination. For this purpose, cholecystokinin was adsorbed onto a C18 reverse-phase column and eluted with acetonitrile. Cholecystokinin standards (10-50 pg) were subjected to the above procedure, which allowed a 20- to 50-fold concentration of the peptide with an 80% recovery. Potassium-induced release of cholecystokinin from minislices of dorsal and ventral regions of the bed nucleus of stria terminalis was measured successfully using the above procedure to concentrate the peptide. Lesion of the stria terminalis, a fiber tract originating in the amygdala, provoked a significant decrease in cholecystokinin levels in the ventral region of the bed nucleus of strial terminalis. Thus, cholecystokinin released from minislices of the ventral region of the stria terminalis may be of amygdaloid origin. PMID- 8517869 TI - Oxidative stress in cultured hepatocytes exposed to acetaminophen. AB - The effect of acetaminophen (APAP) exposure on the formation of oxidized glutathione (GSSG) was investigated in cultured mouse hepatocytes to determine if oxidative damage is involved in the toxicity of this drug. Incubations of hepatocytes for 24 hr with 1 mM APAP produced a time-dependent loss of cell viability which was preceded by depletion of reduced glutathione (GSH) and an increase in GSSG formation. Pretreatment with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) (0.1 mM) for 30 min, which irreversibly inhibited glutathione reductase (GSSG-Rd) activity, increased the extent of GSSG formation produced by APAP exposure and potentiated its cell killing. Pretreatment of hepatocytes with 20 mM deferoxamine (DFO) for 1 hr to chelate ferric iron decreased GSSG formation and cell killing produced by APAP. Pretreatment with BCNU or DFO did not affect APAP oxidation as determined by the formation of the APAP-GSH conjugate or the covalent binding of APAP metabolites to cellular protein. Hence, increasing the susceptibility of hepatocytes to an oxidative stress with BCNU increased both the formation of GSSG and cell killing produced by APAP. Conversely, decreasing their susceptibility to an oxidative stress by chelating iron with DFO decreased GSSG formation and cell injury. It follows that APAP toxicity involves oxidative processes that occur early in the poisoning process and are a major factor contributing to injury in these cells. PMID- 8517870 TI - Oxidation of alpha-tocopherol in subcellular fractions from rat brain and its possible involvement in nerve function. AB - The turnover rate of vitamin E is slow in nerve tissue. Therefore, we have developed in vitro techniques to study the biochemical reactions of this nutrient in brain. Subcellular fractions were isolated from the cerebral hemispheres of 4 month-old, male, Fisher 344 rats. Aliquots of fractions (500 micrograms protein) were suspended in 50 mM phosphate buffer at pH 7.4 and incubated at room temperature (20-22 degrees) or 37 degrees for 2 hr in the presence or absence of the following oxidizing agents: 1 mM tertiary butyl hydroperoxide, 10 microM linoleic acid hydroperoxide, 0.5 to 50 mM 2,2'-azobis (2-amidinopropane) dihydrochloride (ABAPH) or 0.1 to 2 mM 2,2'-azobis (2,4-dimethyl) valeronitrile (ABDVN). The latter two compounds generate free radicals upon heating. After oxidation, the subcellular fractions were sedimented, saponified and assayed for tocopherol by liquid chromatography. Linoleic acid hydroperoxide was the most potent oxidizing agent, suggesting that endogenous fatty acid peroxides (e.g. eicosanoid intermediates) are very powerful oxidizing agents. Vitamin E may play an important role in providing antioxidant protection for membranes against excessive oxidation induced by these peroxides. Tocopherol in mitochondria and microsomes was much more susceptible to oxidation than synaptosomal tocopherol. The possible reasons for this observation are: (a) mitochondria and microsomes may contain less of the other reducing agents such as sulfhydryl compounds than synaptosomes, and/or (b) the electron transport structures in the former two subcellular fractions may be facilitating oxidation of tocopherol induced by free radicals. A portion of tocopherol remained unoxidized in all subcellular fractions even at high concentrations of ABAPH, suggesting that tocopherol exists in labile and nonlabile biochemical compartments or complexes. PMID- 8517871 TI - Contrasting molecular cytotoxic mechanisms of mitomycin C and its two analogs, BMY 25282 and BMY 25067, in isolated rat hepatocytes. AB - The molecular cytotoxic mechanisms of mitomycin C (MMC) and its analogs, BMY 25282 and BMY 25067, have been investigated using isolated hepatocytes as a model system for studying toxicity to nondividing tissues. These drugs have quinone and aziridine moieties, and tumor cell cytotoxicity has been attributed to DNA alkylation and cross-linking. By contrast, the following results suggest that these drugs cause oxidative stress in nondividing cells by different mechanisms. Both hepatocytes or hepatic microsomes and NADPH were able to catalyse oxygen activation by all three drugs, suggesting that enzymatic reduction results in the formation of auto-oxidizable species. Their relative effectiveness at activating oxygen was BMY 25282 >> BMY 25067 > MMC. However, their relative cytotoxic effectiveness was BMY 25067 >> BMY 25282 > MMC, and it was increased markedly if hepatocyte glutathione-reductase or catalase was inactivated. Furthermore, ascorbate increased the toxic potencies of both BMY 25282 and MMC in catalase inactivated hepatocytes by as much as 60- and 40-fold, respectively. Hepatocyte glutathione (GSH) oxidation was also increased. The relative resistance of normal hepatocytes to MMC and BMY 25282 can be attributed therefore, to the high levels of enzymes in hepatocytes involved in hydrogen peroxide detoxification. BMY 25067 cytotoxicity unlike that of BMY 25282 or MMC was prevented by the addition of the thiol reductant dithiothreitol. BMY 25067 also differed in being much more toxic towards GSH-depleted hepatocytes. Furthermore, BMY 25067, unlike MMC and BMY 25282, caused a rapid decrease in hepatocyte ATP levels and inhibited mitochondrial respiration. This could be prevented by the addition of the thiol reductant dithiothreitol, which restored intracellular GSH levels. Its toxic potency to catalase- or glutathione reductase-inactivated hepatocytes also was not increased by ascorbate. Therefore, the cytotoxicity of BMY 25067 can probably be attributed to oxidative stress by the aminodisulfide moiety which causes GSH and mixed disulfide formation, resulting in mitochondrial toxicity. PMID- 8517872 TI - Effect of okadaic acid on human basophil secretion. AB - We examined the effects of a phosphatase inhibitor, okadaic acid, on mediator secretion from human basophils. These cells are known to respond to a number of stimuli that appear to utilize distinct biochemical pathways converging on mediator release. Okadaic acid was found to inhibit IgE-mediated release (histamine release inhibited 80 +/- 12% and leukotriene release inhibited 100% following a 10-min preincubation with okadaic acid and stimulation with an optimal concentration of anti-IgE antibody) at a concentration of 1 microM. The concentration-response curve to okadaic acid was steep, with 0.1 microM yielding only 20 +/- 10% inhibition of either mediator. Secretion following stimulation with the univalent stimulus, fMet-Leu-Phe peptide, was not inhibited by okadaic acid. Unlike cAMP-active agents that inhibit cytosolic Ca2+ elevations following IgE-mediated stimulation, the increased state of cellular protein phosphorylation, which presumably results from treatment with 1 microM okadaic acid, had no effect on the elevations in free cytosolic Ca2+ that follow stimulation with anti-IgE antibody of fMet peptide. PMID- 8517873 TI - Differential responses of rat hepatic microsomal carboxylesterase isozymes to glucocorticoids and pregnenolone 16 alpha-carbonitrile. AB - Differences in the responses to glucocorticoids and pregnenolone 16 alpha carbonitrile (PCN) of three isozymes of hepatic microsomal carboxylesterase, namely RL1, RL2 and RH1, in male rats were studied. The administration of dexamethasone dose-dependently increased isocarboxazid hydrolase activity, whereas p-nitrophenyl acetate-hydrolyzing activity was decreased dose dependently. Betamethasone, methylprednisolone and PCN also markedly increased isocarboxazid hydrolase activity. A radial immunodiffusion assay indicated that carboxylesterase reactive with antibodies was induced by these steroids. Carboxylesterase isozyme RL2 was strongly induced by dexamethasone, methylprednisolone and PCN. In contrast, RL1 and RH1 were decreased by dexamethasone, but not by the other steroids. Estradiol benzoate had a synergic effect on the PCN-induced increase of isocarboxazid hydrolase, but the actions of the glucocorticoids were not affected. It is concluded that hepatic microsomal carboxylesterase isozymes in rats differ considerably from each other in their response to various steroids. These data are also indicative of the importance of glucocorticoids in hepatic xenobiotic metabolism. PMID- 8517874 TI - Effect of substituting fluorine for hydrogen at C-26 and C-27 on the side chain of 1,25-dihydroxyvitamin D3. AB - Previous reports have demonstrated that introduction of fluorine atoms at C-26 and C-27 of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) results in the potentiation of various aspects of some biological activities. The higher biological activities of 26,26,26,27,27,27-hexafluoro- 1,25-dihydroxyvitamin D3 (26,27-F6 1,25-(OH)2D3) were accounted for in part by a decrease in metabolic inactivation via the 26- and 27-hydroxylation pathways. In addition to 26,27-F6-1,25-(OH)2D3 not being hydroxylated in the 26 and 27 positions, it did not undergo 24 hydroxylation despite a significant induction by 26,27-F6-1,25-(OH)2D3 of 24 hydroxylase activity in the HL-60 cell system. Another fluorinated vitamin D3 analog, 26,26,26,27,27,27-hexafluoro-1 alpha-hydroxyvitamin D3 (26,27-F6-1 alpha OH-D3) may not undergo 25-hydroxylation as efficiently as 1 alpha-OH-D3 in vivo because a rise in serum 26,27-F6-1,25-(OH)2D3 levels after injection of 26,27-F6 1 alpha-OH-D3 was delayed significantly with a much smaller amplitude. Furthermore, 26,26,26,27,27,27-hexafluoro-1,23(S),25-trihydroxyvitamin D3 retained full activity in the induction of HL-60 cell differentiation even after 23(S)-hydroxylation, in contrast to 1,23(S),25-(OH)3D3. These data suggested that substitution of fluorines for hydrogens at C-26 and at C-27 positions may result in alteration in chemical reactivity and/or conformation of C-23, C-24 and C-25 positions of the 1,25-(OH)2D3 molecule. PMID- 8517875 TI - Partial agonist properties of rauwolscine and yohimbine for the inhibition of adenylyl cyclase by recombinant human 5-HT1A receptors. AB - Previous studies by another group have suggested that the alpha 2-adrenergic receptor antagonist rauwolscine may function as an agonist at the serotonin1A (5 HT1A) receptor expressed in human brain. To directly test that hypothesis, we transfected the human 5-HT1A receptor cDNA into CHO cells and examined the ability of rauwolscine and its isomer, yohimbine, to inhibit ligand binding of [3H]-(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and the activity of adenylyl cyclase in membranes derived from a single transformant that stably expresses approximately 225 fmol of 5-HT1A receptor/mg of membrane protein. Both ligands competitively antagonized the binding of [3H]8-OH-DPAT (Ki = 158 +/- 69 nM for rauwolscine and 690 +/- 223 nM for yohimbine), yielding shallow displacement curves consistent with agonist activity (Hill values = 0.69 +/- 0.2 for rauwolscine and 0.63 +/- 0.06 for yohimbine). Both ligands also inhibited forskolin-stimulated adenylyl cyclase activity in membranes derived from transfected (but not nontransfected) cells. For rauwolscine, the IC50 was 1.5 +/- 0.2 microM, and for yohimbine 4.6 +/- 1.0 microM, with activity ratios of 0.70 and 0.59, respectively, when compared to the full agonist serotonin. These studies demonstrated that rauwolscine and yohimbine are partial agonists for the human 5-HT1A receptor. PMID- 8517876 TI - Reversal of the inhibitory effects of calcitonin gene-related peptide (CGRP) and amylin on insulin secretion by the 8-37 fragment of human CGRP. AB - The 8-37 fragment of human calcitonin gene-related peptide [(8-37)hCGRP] antagonizes the effects of calcitonin gene-related peptide (CGRP) and amylin in a number of tissues. We have studied the influence of (8-37)hCGRP on the effects of both CGRP and amylin on insulin secretion. In the perfused rat pancreas, homologous CGRP and amylin, at 75 pM, exerted comparable inhibitory effects on the insulin response to 9 mM glucose (ca. 70%; P < 0.025). These effects were antagonized by (8-37)hCGRP (1 microM). Our results suggest that CGRP and amylin act on the B-cell, at least in part, through a common receptor. PMID- 8517877 TI - Inhibition of binding of basic fibroblast growth factor to low and high affinity receptors by carrageenans. AB - The effect of carrageenans, a family of polysulphated polysaccharides, on the binding of basic fibroblast growth factor (bFGF) to low affinity (heparin-like) receptors and high affinity receptors on baby hamster kidney cells was investigated. kappa-, iota-, and lambda-carrageenans all inhibited binding of bFGF to both types of receptors with iota-carrageenan being the most potent inhibitor (IC50 values of approx. 0.7 and 4 micrograms/mL for inhibition of binding to low and high affinity receptors respectively). Heparin reduced the inhibition of bFGF binding to high affinity receptors caused by iota-carrageenan. Heparin and iota-carrageenan were comparable in their activities at displacing pre-bound bFGF from both low affinity receptors and high affinity receptors. These results indicate that iota-carrageenan binds to the heparin-binding domain on bFGF and that this may be sufficient to reduce the ability of bFGF to bind to high affinity receptors. PMID- 8517878 TI - Drug concentrations in mouse brain at pharmacologically active doses of fluoxetine enantiomers. AB - The i.p. injection of R-fluoxetine into mice at doses of 1-10 mg/kg led to higher concentrations of the desmethyl metabolite, R-norfluoxetine, in whole brain than was true for S-fluoxetine. R-Norfluoxetine, but not S-norfluoxetine, concentrations predominated over those of the parent drug at 7-24 hr after injection of the corresponding fluoxetine enantiomer. The more rapid N demethylation of R-fluoxetine, and the relative inactivity of R-norfluoxetine as a serotonin uptake inhibitor compared with S-norfluoxetine, may explain the earlier report that R-fluoxetine is less potent than S-fluoxetine in antagonizing p-chloroamphetamine depletion of brain serotonin in mice. In the present study, a 10 mg/kg, i.p., dose of S-fluoxetine completely prevented p-chloroamphetamine given 24 hr later from depleting brain serotonin, whereas R-fluoxetine offered no protection at this time. PMID- 8517879 TI - Effect of glutathione depletion on the conversion of xanthine dehydrogenase to oxidase in rat liver. AB - The ability of endogenous glutathione (GSH) to modify the activity of the enzyme xanthine oxidase (XO) in rat liver was investigated. The effect of hepatic GSH depletion on the conversion of xanthine dehydrogenase (XDH) (EC 1.1.1.204) to XO (EC 1.1.3.22) was determined 10 min after i.p. administration of different amounts of diethylmaleate to fasted rats. After administration of 400 mg/kg, total hepatic non-protein GSH (reduced + oxidized GSH) decreased significantly to 14% of controls. In this condition the level of oxidized GSH was unchanged and no lipid peroxidation was observed, while a significant increase of reversible XO and a minor increase of the irreversible form of the enzyme was detected. PMID- 8517880 TI - Update of ANNA's Long-Range Strategic Plan by Board of Directors. AB - In 1990, the American Nephrology Nurses' Association (ANNA) developed its Long Range Strategic Plan (LRSP), an important tool that included both short and long range goals. In order to achieve the goal of strategic planning, the working tool must be usable, flexible, and current. The following is a revision of the LRSP drafted by the ANNA Board of Directors in 1992. PMID- 8517881 TI - Primary physicians and primary care. PMID- 8517883 TI - Ethanol impairs neutrophil chemotaxis in vitro but not adherence or recruitment to lungs of rats with experimental pneumococcal pneumonia. AB - The effect of 7 days of ethanol ingestion on circulating neutrophil (PMNL) counts and PMNL adherence, chemotaxis, and recruitment was investigated. Pair-feeding of rats resulted in a significant decrease in PMNL counts in both ethanol-fed and control rats. The mean number of PMNL exhibiting chemotaxis in a modified Boyden chamber in response to lipopolysaccharide-activated normal rat serum was significantly decreased in ethanol-fed rats compared with controls. The percentage of adherence to nylon wool columns, however, was similar in both groups. To measure pulmonary PMNL recruitment, rats were infected transtracheally with 10(5) Streptococcus pneumoniae and sacrificed. Bronchoalveolar lavage fluid from both groups contained similar numbers of PMNL 8 h after infection. By 24 h, PMNL numbers in lavage fluid from ethanol-fed rats exceeded those in controls. PMNL recruitment continued in the ethanol-fed rats at 48 and 72 h, whereas values in controls had returned to baseline. Thus, the impaired pulmonary defense against S. pneumoniae in ethanol-fed rats is not due to defective PMNL recruitment. PMID- 8517882 TI - The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5' flanking sequence of lamp-2 gene and comparison of exon organization in two genes. AB - Human lysosomal membrane glycoproteins lamp-1 and lamp-2 are the major sialoglycoproteins present in lysosomal membranes. The expression of lamp-2 molecules is uniquely regulated, whereas lamp-1 is constitutively synthesized. In order to investigate the unique expression of lamp-2, and the gene evolution of lamp-1 and lamp-2, we isolated genomic phage clones encoding these glycoproteins. Comparison of the genomic and cDNA sequences revealed that the lamp-2 gene consists of nine exons. The transcriptional start site of the lamp-2 gene was determined by primer extension analysis. In order to locate the transcriptional regulatory region of this gene, various regions of 5'-sequences were tested for promoter activity using chloramphenicol acetyltransferase as a reporter molecule. The results revealed that the 5'-flanking sequence from -172 to -20 base pairs has strong promoter activity. In this sequence, potential SP1 and AP-1 binding sites and CAAT boxes are found. Most notably, the promoter activity is suppressed if the 5' farther upstream KpnI repeat sequence is included in the tested 5' flanking sequence, thus suggesting that the KpnI repeat sequence may have some regulatory function in the lamp-2 gene expression. Comparison of the exon organization of human lamp-2 and lamp-1 genes, or chicken lamp-1 gene, reveals that these two proteins utilize the same exon phase in corresponding introns. Furthermore, each exon encodes almost identical portions of the proteins. On the other hand, the amino acid sequence of human lamp-1 is more homologous to lamp-1 of other species than it is to human lamp-2. These results indicate that lamp-1 and lamp-2 genes were most likely produced by duplication of a primordial gene, which took place early in evolution. PMID- 8517884 TI - Aldehyde dehydrogenase in blood: distribution, characteristics and possible use as marker of alcohol misuse. PMID- 8517885 TI - The relationship between alcohol dependence and depression. AB - Alcohol dependence is not a unitary or homogeneous disorder. There is substantial evidence to suggest that in both community and particularly in clinical samples, additional psychopathology is common. Although estimates of additional psychopathology differ according to the samples studied and the instruments used to classify disorders, up to two-thirds of clinical samples of patients with alcohol dependence are likely to have a lifetime diagnosis of another psychiatric disorder. Affective disorder and antisocial personality disorder appear to be the most commonly and consistently reported additional disorders. Women more than men appear to suffer from additional psychopathology, including secondary and primary depression, although this evidence is weakened by there being fewer studies carried out on mixed gender populations. Having an additional psychiatric diagnosis appears to alter the course of alcohol dependence: it may hasten the development of dependence on alcohol and may bring individuals to the attention of treatment agencies more quickly. More recent studies have examined the relationship between alcohol dependence and affective disorder in the current episode. There is consistent evidence to suggest that a diagnosis of depression in the current episode may change to one of alcohol dependence alone, once detoxification or abstinence has been achieved. The prognosis of those who continue to be depressed remains unclear. PMID- 8517886 TI - Effects of various serotonergic agents on alcohol intake and alcohol preference in Wistar rats selected at two different levels of alcohol preference. AB - Wistar rats can develop a high preference for 3% alcohol after a period of forced alcohol exposure and 2 days of alcohol withdrawal. If these rats are selected at a medium (> or = 60%) and a high (> or = 85%) level of alcohol preference, it is possible to study the effects of various compounds on alcohol intake and alcohol preference in rats with two different levels of alcohol preference. With this procedure, it was demonstrated that the benzodiazepine chlordiazepoxide can reduce alcohol preference at doses > or = 10.0 mg/kg in the high alcohol preference group, by increasing the water consumption without affecting alcohol drinking. Chlordiazepoxide had no effects in the medium alcohol preference group. The 5-HT uptake inhibitors fluoxetine and citalopram reduced alcohol intake and alcohol preference in both the medium and the high alcohol preference groups by means of a reduction in consummatory behaviour. Both drugs clearly affected total fluid intake and body weight gain. The 5-HT1A agent buspirone reduced alcohol intake and alcohol preference in the group of medium alcohol preferring rats at doses between 0.0025 and 0.63 mg/kg. The drug did not change water drinking so that total fluid consumption diminished. At doses > or = 2.5 mg/kg buspirone, there was an increased alcohol consumption. Buspirone was without important effects on the high alcohol preferring rats. The 5-HT3 antagonist ondansetron reduced alcohol intake in both the medium and high alcohol preferring rats at doses between 0.01 and 0.16 mg/kg. The drug had no effects on alcohol preference and water consumption. At some doses, there was a reduction in total fluid intake. The 5-HT2/1C antagonist ritanserin reduced alcohol intake and alcohol preference at doses between 0.04 and 2.50, and 0.16 and 10.0 mg/kg in the medium and high alcohol preferring rats, respectively. Together with the decrease in alcohol consumption there was an increase in water drinking, leaving total fluid intake unaffected. The activity of ritanserin was less pronounced in the high as compared to the medium alcohol preference group. These results indicate that various serotonergic agents can affect alcohol intake and alcohol preference by different mechanisms of action. PMID- 8517887 TI - Monitoring of ethanol levels in the rat nucleus accumbens by brain microdialysis. AB - Brain microdialysis was used to measure nucleus accumbens (NAC) ethanol (EtOH) over several hours after intraperitoneal (i.p.) injection of EtOH. Levels of EtOH in NAC perfusates were assayed by gas chromatography. Peak EtOH levels were observed 40 min after the injection and the three doses of EtOH, 0.5, 1.0, and 2.0 g/kg, resulted in peak perfusate levels of 5 mM, 18 mM, and 38 mM, respectively. Measurement of regional brain EtOH levels may prove useful for studying the relationship between patterns of alcohol consumption and the action of EtOH in the central nervous system. PMID- 8517888 TI - Alcohol exposure before pregnancy: effect on GABA levels and turnover in rat offspring. AB - The GABA levels and turnover rates in various brain areas from 2-month-old rats born to mothers who consumed 20% (v/v) alcohol during 1 month only before pregnancy, were investigated. A decreased level was found in the olfactory tubercules and an increase was observed in the hypothalamus. The turnover rates were reduced in both areas, whereas an increase was observed in the frontal cortex. These results indicate that biochemical alterations may occur in the offspring even if the fetus did not develop under alcoholization. PMID- 8517889 TI - Antibrain antibodies in alcoholic patients. AB - Sera of 30 chronic alcoholic patients and 30 age-matched and gender-matched controls were examined for antibodies to brain tissues. We performed an indirect immunofluorescence assay using the patients' and controls' sera as first antibodies, and fluorescein-conjugated anti-human-immunoglobulin Ig-A,Ig-G and Ig M as second antibodies, on frozen sections of normal human brain. Binding to neuronal cell nuclei of frontal cortex and septal area was found in 40% of patients, but only in 6.7% of controls. The antibodies belonged to the IgM, and additionally sometimes the IgA and IgG subclass. The relevance of these antibodies for the development of brain disease in chronic alcoholic patients is discussed. PMID- 8517890 TI - The ethics and safety of alcohol administration in the experimental setting to individuals who have chronic, severe alcohol problems. AB - There is a popular belief that the experimental administration of alcohol to individuals who have chronic, severe alcohol problems ('alcoholics') is inherently dangerous or unethical. This creates an environment in which researchers who desire to conduct a study involving the administration of alcohol to persons with severe alcohol problems must defend the relative safety and reasonableness of this practice when, in fact, scientific justification for not using this important methodologic technique in alcohol research is lacking. The primary purpose of this manuscript is to present and discuss the safety, ethical, and practical considerations of research involving administration of alcohol to subjects who have had difficulty refraining from harmful alcohol use in the natural setting. The authors also describe a study in which they monitored the short-term effects of administering 0.4-0.6 g/kg alcohol to 16 recently abstinent subjects who had chronic, severe alcohol problems. This study revealed no evidence that the administration of beverage alcohol in the experimental setting to such individuals causes an uncontrollable desire for more alcohol, precipitates immediate relapse, or creates any behavioral problems. The data also suggested that the knowledge gained from the effects of alcohol ingestion in the experimental setting might help many subjects to understand more completely their addiction or drinking behaviour. It is concluded that there is no overriding reason why alcohol cannot, with due precaution, be safely and ethically administered in the experimental setting to human subjects who suffer from alcohol problems. PMID- 8517891 TI - Wernicke's encephalopathy, Korsakow's amnesic state and thiamine deficient encephalopathy. PMID- 8517892 TI - What do parents of preterm infants know about diphtheria, tetanus, and pertussis immunizations? AB - Preterm infants often receive immunizations late or in reduced dosage. The purpose of this study was to describe the knowledge of parents of preterm infants about immunizations. We sent a questionnaire to the parents of preterm infants who attended our Neonatal Follow-up Clinic. Of the 112 families who returned the survey, only 45% correctly answered that preterm infants should be immunized at the same age as full-term infants. Nearly 40% of parents stated that "how premature the baby was" influenced time of immunization. Over 25% reported that the infant had to reach a minimum weight to be immunized. Parents who received information from neonatal intensive care or Neonatal Follow-up Clinic staff or a public health nurse were not more correctly informed about immunizations. Parents of prematures often are not correctly informed about immunizations. Information about immunizations for preterm infants should be incorporated into NICU discharge planning. PMID- 8517893 TI - Systemic hypertension in infants with severe bronchopulmonary dysplasia: associated clinical factors. AB - The clinical course of 87 infants with bronchopulmonary dysplasia (BPD) on home oxygen therapy was reviewed to determine the occurrence of systemic hypertension (HTN) and to evaluate associated clinical features. Eleven of 87 (13%) infants developed systemic HTN either in the neonatal intensive care unit or following discharge. Clinical features that distinguished the hypertensive from the normotensive group were as follows: greater use of bronchodilators, 91% vs 37% (p < 0.001), and diuretics, 91% vs 55% (p < 0.05), longer duration of home oxygen therapy 21.6 +/- 9.9 vs 9.2 +/- 5.8 months (p < 0.05), and greater mortality, 36% vs 1% (p < 0.001). The course of systemic HTN in the surviving patients (7 of 11) was benign and resolved in all patients prior to weaning from home oxygen therapy. Systemic HTN is frequently present in infants with severe BPD and appears to be related to the clinical severity of lung disease. PMID- 8517894 TI - Antenatal diagnosis of congenital dislocation of the knee: a case report. AB - Congenital dislocation of the knee was diagnosed antenatally in an abdominal flat plate. This is probably the first time that this condition has been diagnosed prior to delivery. Examination of the newborn after delivery revealed dislocation of the right hip and knee. The obstetric and orthopedic implications and suggested treatment are discussed. PMID- 8517895 TI - Fetal central blood flow alterations in human fetuses with umbilical artery reverse diastolic flow. AB - Blood flow velocimetry studies in animal fetuses with reverse diastolic flow in the umbilical artery have shown marked changes in the fetal central circulation characterized by a retrograde diastolic flow in the descending aorta, and as far as the aortic arch, along with a significant forward diastolic flow in the arteries going to the brain. Documentation and the implications of this phenomenon in human fetuses, to date, have not been reported. Doppler echographic evaluations of the diastolic patterns in the umbilical artery, descending aorta, the aortic arch, and the common carotid artery were performed on 5 fetuses in whom reverse diastolic flow was observed in the umbilical artery. In all five cases reverse diastolic flow was observed not only in the umbilical artery but also in the aortic arch. In the carotid artery, however, a forward diastolic flow was always recorded. It can be concluded, by inference, that in these fetuses, the area of lowest resistance was no longer the placenta, as seen in normal conditions, but the cerebral circulation. Furthermore, in four fetuses the retrograde component of the flow profiles was more prominent in the aortic arch compared with the descending aorta, suggesting that, in diastole, blood was coming from the pulmonary artery through the ductus arteriosus. PMID- 8517896 TI - Intrauterine tachycardia and periventricular leukomalacia. AB - We describe a preterm infant of 32 weeks' gestation with hydrops fetalis due to intrauterine supraventricular tachycardia. On the second day of life, cranial ultrasound showed a mainly right-sided periventricular leukomalacia already with porencephalic cysts. These findings were confirmed by autopsy. An association of intrauterine tachycardia with periventricular leukomalacia must be assumed. PMID- 8517897 TI - Prenatal sonographic diagnosis and clinical management of small bowel obstruction. AB - A case of prenatal sonographic diagnosis of fetal small bowel atresia at 31 weeks of gestation is described. At explorative laparotomy following delivery, an "apple peel" type of jejunal atresia was found. The etiology, diagnosis, and clinical management of fetuses with small bowel atresia are discussed. PMID- 8517898 TI - Medical therapy for the hydropic fetus with congenital complete atrioventricular block. AB - Early delivery, immediate ventricular pacing, and inotropic support have failed to improve the outcome of hydropic fetuses with congenital complete atrioventricular block. On detection of hydrops, two fetuses were treated with maternally administered digoxin and furosemide with prompt and sustained resolution of intrathoracic fluid accumulations. Clearance of serosal fluid collections may prevent pulmonary hypoplasia and improve cardiac function. Before proceeding with premature delivery in such patients, a brief trial of transplacental anti-congestive therapy is indicated. PMID- 8517899 TI - Urinary endothelin-1-like immunoreactivity excretion in the newborn period. AB - Urinary endothelin-1-like immunoreactivity (ET-1-LI) excretion was determined in 31 neonates, six sick infants with renal dysfunction secondary to neonatal asphyxia and 25 healthy infants, during the first week of life to clarify its evolutional change and the origin of the urinary ET-1-LI in the newborn period. Urinary ET-1-LI concentrations in the healthy infants maintained the same level during the first week of life (n = 35, 36 +/- 22 pg/mg creatinine, mean +/- SD). There was no difference in urinary ET-1-LI excretion in infants between 30 and 41 weeks of gestation. Urinary ET-1-LI concentrations in the sick infants were significantly elevated through the first week of life when compared with those of healthy infants. Fractional excretion of sodium and endothelin clearance were more elevated in the sick infants than in the healthy infants. A good correlation was observed between urinary ET-1-LI concentrations and urinary N-acetyl-beta-D glucosaminidase index (r = 0.72, p < 0.01). These results suggest that the origin of urinary endothelin-1 may be the renal tissue and that ET-1 may be a nonspecific marker of renal injury in neonates. PMID- 8517900 TI - Discordancy in triplets. AB - Discordancy in twins is generally described as a weight difference between the fetuses of 15 to 25% and its prevalence in normal twin gestations is estimated at 15 to 29%. The present study was performed in order to determine the frequency of discordant newborns in uncomplicated triplet gestations. One hundred and fourteen normal triplet newborns were delivered during a period of 11 years. Their birthweight ranged from 493 to 2533 gm, with a mean of 1894.2 +/- 468.5 gm (+/- sd). In 58% of these 38 sets of triplets the difference in weight between the largest and smallest newborn was more than 15%. About a quarter of the newborns had a greater than 25% dissimilarity in their birthweights. There was no substantial fetal-fetal transfusion or difference in the Apgar scores between the discordant fetuses. It may be concluded that triplet newborns have a rate of discordancy double that of twins. Discordance per se does not necessarily mark an underlying complication of pregnancy or a bad perinatal outcome. PMID- 8517901 TI - Sonographic measurement of the fetal mandible: standards for normal pregnancy. AB - Measurements of the fetal mandible were made on 204 women with uncomplicated pregnancies and reliable gestational dates. The measurements were made in the sonographic plane, which included the fetal mandible and the hypopharynx. The antero-posterior and transverse jaw measurements increased with gestational age (p < 0.0001), and correlated well with both the biparietal diameter and femur length (p < 0.0001). Measurements were technically more difficult to obtain during the late third trimester. These standards for fetal jaw measurement may be useful in the sonographic identification of micrognathia. PMID- 8517902 TI - Effect of adding heparin in very low concentration to the infusate to prolong the patency of umbilical artery catheters. AB - A randomized controlled study was done to determine whether the addition of heparin, in very low concentration (0.25 U/ml), to fluids administered through an umbilical artery catheter (UAC) would affect the duration of catheter patency. UAC occlusion occurred in 2 of 15 patients in the heparin group and in 11 of 15 patients in the control group (p = 0.001). Using life-table analysis, the functional life span of UAC was estimated. On day 8, 100% of UACs in heparin group and 9% of UACs in control group were patent (p < 0.05). Coagulation profile remained unaltered after addition of heparin compared with that before the start of the therapy. There was no difference in the incidence of subependymal intraventricular hemorrhage between the two groups. It is concluded that heparin in such low concentration is effective in prolonging duration of UAC patency without causing adverse effects. PMID- 8517903 TI - Phenytoin versus magnesium sulfate in preeclampsia: a pilot study. AB - A randomized clinical trial was designed to determine whether there are clinically demonstrable advantages of phenytoin over magnesium sulfate in preeclamptic patients because of the latter drug's uterine relaxant properties. An intravenous infusion, immediately after randomization, of either phenytoin or magnesium sulfate, with subsequent measurement of serum concentrations and maintenance of therapeutic levels was given to 103 preeclamptic and two eclamptic women. Observed were the rate of cervical dilation during active labor and change in hematocrit between predelivery and 24-hour postdelivery values and the incidence of side effects ascertained by interview. Compared with those receiving magnesium sulfate, patients receiving phenytoin had more rapid cervical dilation (3.3 cm/hr versus 1.5 cm/hr, p = 0.016) and a smaller fall in hematocrit after delivery (-4.7% versus -7.6%, p = 0.034). A significantly lower incidence of hot flushes (15% versus 46%, p < 0.005) and a trend toward less dyspnea and weakness were reported by phenytoin-treated patients. Our phenytoin regimen produced acceptable serum phenytoin levels (10 to 25 micrograms/ml) in 96% of patients. PMID- 8517904 TI - Sonographic growth curves of triplet conceptions. AB - The diagnosis of inappropriate intrauterine fetal growth in triplet pregnancies requires normal standard sonographically determined growth curves. The aim of the present study was to establish such nomograms. The biparietal diameter (BPD), femur length, head and abdominal circumferences (HC, AC) were once in 3 weeks sonographically evaluated in 108 normal triplet fetuses. The resulting growth curves were compared with those of normal singleton fetuses. The data showed that, compared with singletons, the mean triplet fetal BPD progressively lags to a maximum of 2 1/2 weeks as pregnancy continuous from the 25th to the 36th gestational week. Similarly, mean femur length of triplet fetuses gradually shortfalls to the greatest of 2 weeks as gestation advances from the 25th to the 36th week. HC to AC ratio of the triplet fetuses does not differ from the singletons curve. It may be concluded that a normal fetal growth curve in triplet pregnancies demonstrates a 1- to 3-week delay compared with singleton gestations. PMID- 8517905 TI - Maternal cerebral vasospasm in eclampsia assessed by transcranial Doppler. AB - We report a case of postpartum eclampsia in which the patient was assessed during delivery and postpartum by maternal cerebral transcranial Doppler ultrasound. We provide documentation of the changes in the cerebral blood flow velocity with the development of eclampsia. PMID- 8517906 TI - Is an abnormal Doppler umbilical artery waveform ratio a risk factor for poor perinatal outcome in the non-small for gestational age fetus? AB - To determine if abnormal umbilical artery velocimetry is associated with a higher rate of perinatal morbidity in pregnancies in which the outcome is not manifested by a small for gestational age (SGA) fetus, perinatal outcome was compared according to the results of Doppler umbilical artery velocimetry. Doppler study was performed in 328 singleton pregnancies with non-SGA fetuses within 7 days of delivery. The prevalence of abnormal Doppler studies was 10%. Patients with abnormal umbilical artery velocimetry had a significantly higher rate of complications, including cesarean section for fetal distress, preterm delivery, low Apgar scores, congenital anomalies, admission to the neonatal intensive care unit, and perinatal death, than patients with a normal umbilical artery velocimetry. Ten perinatal deaths were associated with major congenital anomalies. Moreover, in the absence of congenital anomalies patients with abnormal Doppler results also had a significantly higher incidence of adverse perinatal outcome compared with patients with normal umbilical artery velocimetry. Our data suggest that even the non-SGA fetus with an abnormal Doppler umbilical artery waveform ratio is at increased risk for poor perinatal outcome. PMID- 8517907 TI - Validation of arterial oxygen saturation measurements in utero using pulse oximetry. AB - The noninvasive measurement of fetal arterial oxygen saturation using pulse oximetry could be of potential use in assessing fetal well-being in utero during labor. In this study, the accuracy and technical feasibility of reflectance pulse oximetry in utero was evaluated in acutely instrumented fetal sheep using a specially designed sensor. Following recalibration of the analysis algorithms, fetal arterial saturation could be measured by pulse oximetry in utero. Arterial oxygenation measurements obtained using pulse oximetry correlated well with simultaneous in vitro measurements over the range of 6 to 81%. We conclude that in utero pulse oximetry is technically feasible, appears useful and accurate, and merits further evaluation. PMID- 8517908 TI - Situs inversus abdominis in association with duodenal obstruction and internal hernia. AB - Persistent bile-stained vomiting in a neonate led to a radiologic workup that revealed the existence of a situs inversus and a partial duodenal obstruction. A duodenal diaphragm with a central aperture was diagnosed. Surgery confirmed the preoperative diagnosis. In addition, an annular pancreas with an anterior gap and a right parietocolic internal hernia containing all the small bowel were discovered. Embryologic aspects, therapeutic options, and the literature were discussed. PMID- 8517909 TI - When should we be sorry? An obstetrician's dilemma. PMID- 8517910 TI - Systemic hypertension in infants with severe bronchopulmonary dysplasia. PMID- 8517911 TI - Pulse oximetry for the validation of arterial oxygen saturation measurements in utero. PMID- 8517912 TI - Design, synthesis, and biological evaluation of DNA sequence and minor groove selective alkylating agents. AB - The syntheses of oligoimidazolecarboxamido analogues of distamycin wherein the N terminus contains either a benzyl-mustard 8 or chlorambucil moiety 9-11 are reported. Based on data from an ethidium displacement assay and CD studies, these compounds, along with the N-benzoyl mustards 6 and 7, were shown to have increased acceptance of GC-rich sequences over distamycin. Compounds 8-11 which contain an electron-donating group (sigma < 0) para to the bischloroethylamino moiety, were found to have significantly enhanced reactivity with DNA compared to the benzoyl mustards 6 and 7. Through dialysis experiments, the benzyl and chlorambucil mustards were shown to alkylate calf thymus DNA more readily than the benzoyl mustards, presumably due to destabilization of the aziridinium intermediate by the electron-withdrawing (sigma > 0) carboxamido group of the benzoyl compounds. Compounds 8-11 were found to alkylate guanine-N7 in the major groove, while compounds 6 and 7 did not, suggesting that they may have different modes of DNA interaction. Mustards 8-11 were also more efficient than 6 and 7 at producing DNA interstrand cross-links in isolated DNA. In general, for these compounds, the cytotoxicity against human chronic myeloid leukemia K562 cells and the panel of human tumor cell lines of the National Cancer Institute increased with the number of imidazole moieties. The IC50 values of compounds 7 and 8 were similar, even though the latter compound was at least 100-fold more efficient at forming DNA cross-links in isolated DNA. Similarly, compounds 9-11 were less cytotoxic than 6 and 7, although they were more efficient cross-linkers in isolated DNA. A direct comparison of the three imidazole-containing benzoyl mustard 7 with the corresponding chlorambucil-containing 11 for their ability to form interstrand cross-links in cells revealed that the former compound showed no cross-linking even at doses in excess of the IC50, whereas the latter produced extensive cross-linking. This further suggests that these compounds exert their biological activity through different mechanisms. It is proposed that the aromatic moiety of compounds 8-11, which bind to the minor groove, may be able to intercalate between GC base pairs and the protruding bischloroethylamino group would be positioned to alkylate and cross-link at guanine-N7 sites in the major groove. However, the benzoyl mustards, which have a rigid amino linkage between the imidazole and aromatic-mustard moieties, do not have the flexibility to intercalate into the DNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8517914 TI - Synthesis and biological activity of novel thymidine derivatives of podophyllotoxin and 4'-demethylepipodophyllotoxin. AB - We have synthesized a number of novel derivatives of podophyllotoxin (POD) and 4' demethylepipodophyllotoxin (DMEP) in which the nucleoside thymidine has been conjugated at the C4 position. To investigate the structure-activity relationship among these compounds, the cross-resistance patterns of these derivatives towards a set of either POD-resistant (PodR) or VP16/VM26-resistant (VpmR) mutants of Chinese hamster ovary (CHO) cells were determined. These mutants exhibit highly specific cross-resistance patterns toward compounds that show either POD- or VP16/VM26-like activity. The observed cross-resistance patterns of the thymidine derivatives suggests that these compounds display POD-like activity in vivo and show no VP16/VM26-like activity. Further, treatment of Chinese hamster cells with these compounds caused a dose-dependent increase in the mitotic index similar to the patterns observed with POD and DMEP, supporting the data from the cross resistance assay. Most thymidine derivatives exhibited much lower activity in comparison to POD or DMEP, suggesting that the thymidine moiety interferes with the interaction of these compounds with the receptor site on the tubulin molecule. One of these derivatives which was most active in the aforementioned assays was also found to be a competitive inhibitor of radiolabelled POD binding to purified bovine brain tubulin. All other compounds were insoluble at concentrations required to perform the competition assay. Molecular modelling studies provide valuable insight regarding the three-dimensional structural requirements that distinguish POD-like compounds from their VP16/VM26-like counterparts. There appears to be a very limited spatial and electrostatic requirement for the bulky glycosidic moiety at C4 which is essential for VP16/VM26-like activity. PMID- 8517913 TI - Antitumor activity of a new low immunosuppressive derivative of podophyllotoxin (GP-11) and its mechanisms. AB - The spin-labeled derivative of podophyllotoxin, N'-podophyllic acid-N-[3-(2,2,5,5 tetramethyl pyrrolinenyloxy)] semicarbazide (GP-11), was synthesized and tested for its antitumor activity against mouse transplantable tumors, Sarcoma-180, Hepatoma-A, P388 leukemia and Ehrlich ascites carcinoma. At an equitoxic dose, the antitumor activity of GP-11 was similar to that of etoposide (VP-16). However, the immunosuppressive effects of GP-11 were weaker than that of VP-16. In vitro, GP-11 and VP-16 inhibited the proliferation of human lymphoid leukemia Molt 4B cells and suppressed DNA and protein syntheses, but the effect of GP-11 and VP-16 on cell cycle progression was different. The mitotic index was increased by GP-11 and reduced by VP-16. On the basis of flow cytometric bromodeoxyuridine (BrdU)/DNA analysis, GP-11 and VP-16 resulted in the accumulation of cells in the S and G2/M phases. G2/M arrest by GP-11 on cell cycle progression was stronger than that of VP-16, while S arrest was weaker than that of VP-16. After the removal of drugs, the arrest by GP-11 and VP-16 still existed and was irreversible. These results may provide insights into the structure-activity relationships and the design of novel derivatives of podophyllotoxin useful in cancer chemotherapy. PMID- 8517915 TI - A theoretical study of the mechanism of oxygen binding by model anthraquinones. Part II. Quantum-mechanical studies of the energetics of oxygen binding to model anthraquinones. AB - Anthracycline derivatives, which constitute an important class of antitumor drugs, exhibit undesirable cardiotoxicity owing to their mediation in the process of oxygen reduction to the superoxide anion radical. Earlier work showed that this mediation could be facilitated by the formation of complexes with the 1 delta g oxygen molecule prior to reduction. In this paper, we investigate the energetics of the possible peroxides formed by a series of model anthraquinones: 1,4-dihydroxyl- (quinizarin), 1,8-dihydroxyl-, 1-hydroxy-8-methoxy-, 1,8 dimethoxy-, 1,4,5-trimethoxy- and 1,4-dihydroxy-5-methoxy-9,10-anthracenedione, as well as of daunorubicin and demethoxydaunorubicin, by semi-empirical quantum mechanical MNDO and PM3 methods, and limited STO-3G ab initio calculations. It was found that the oxygen-binding site is determined by three factors: the high electron density and high HOMO coefficients on the carbon atoms to which oxygen binds, the minimum loss of conjugation within the anthraquinone moiety on oxygen binding and the minimum number of bonds to other heavy atoms of the oxygen binding carbons (the steric effect). For different molecules, the energy of the most stable oxygen complex is the greatest for compounds with the lowest ionization potential. On the basis of this and our earlier studies, it was concluded that the anthracycline derivatives with reduced ability to bind oxygen and, therefore, reduced cardiotoxicity, should possess a high symmetry of II electron density distribution, a high ionization potential and have all of the oxygen-binding sites condensed to other rings or substituted by bulky groups. PMID- 8517916 TI - NOD mouse colonies around the world--recent facts and figures. AB - Non-obese diabetic (NOD) mice are commonly used in autoimmune research. However, the diversity of these mice in developing autoimmune disease under different conditions prompted a group of researchers to compile a questionnaire on this subject. Here Paolo Pozzilli and colleagues comment on the results of this survey. PMID- 8517917 TI - Can AIDS be prevented by T-cell vaccination? AB - T-cell vaccination as a specific prophylactic and therapeutic procedure has been shown to be effective in animal models of autoimmune disease. As autoimmunopathogenic components have been implicated in HIV infection, the authors propose a therapeutic test utilizing T-cell vaccination and suggest that AIDS could be prevented by such a procedure. PMID- 8517918 TI - How do T-cell receptors, MHC molecules and superantigens get together? AB - The current model of superantigen activity assumes that the superantigen simultaneously binds to both the MHC molecule on the presenting cell and the V beta element of the TCR, resulting in crosslinking of both molecules and subsequent activation of the T cell. Here, David Woodland and Marcia Blackman discuss the concept that there is an additional interaction between the TCR and MHC molecule during superantigen engagement and the significant impact this has on superantigen specificity and function. PMID- 8517919 TI - Growth hormone and prolactin are paracrine growth and differentiation factors in the haemopoietic system. AB - The pituitary secretory proteins growth hormone (GH) and prolactin (PRL) do not, as yet, have major roles in haematology or immunology. Recent evidence indicates that these hormones are haemopoietic growth factors and exert immunomodulatory functions at physiological concentrations. Here Robert Hooghe and colleagues discuss the significance of these hormones on different aspects of the immune system. PMID- 8517920 TI - Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. AB - Receptors for the Fc domain of IgG (Fc gamma R) provide a critical link between specific humoral responses and the cellular branch of the immune system. When hFc gamma R interact with immunoglobulin, a variety of biological responses are triggered. These include phagocytosis, endocytosis, antibody-dependent cellular cytotoxicity (ADCC), release of inflammatory mediators, and enhancement of antigen presentation. In the last few years our understanding of the Fc gamma receptor structure has increased dramatically, due to the availability of monoclonal antibodies (mAb) and cDNA probes. Fc gamma R are members of the immunoglobulin superfamily and three main classes, hFc gamma RI, hFc gamma RII, and hFc gamma RIII are recognized in man generating at least 12 different isoforms. A further level of complexity is introduced by various genetic polymorphisms and, importantly, recent evidence points at the relevance of this Fc gamma R heterogeneity. PMID- 8517921 TI - Signal transduction by Fc receptors: the Fc epsilon RI case. AB - The family of proteins collectively known as Fc receptors (FcR) plays a variety of roles both in the initiation of the immune response and in its consequences. During the past five years the structure of these proteins and the genes that code for them have been largely elucidated. The most unexpected finding has been their extensive diversity. Considerable efforts are now being expended to define the molecular events initiated by these various FcR and these events are the focus of our review. PMID- 8517922 TI - Lymphocyte Fc receptors: the special case of T cells. AB - The different cell types of the lymphoid-myeloid lineage constitutively express various Fc receptors. The exception is the T-cell lineage where most subsets express Fc receptors only during a narrow window following cellular activation. M. Sandor and R.G. Lynch summarize information which identifies a multi-level relationship between Fc receptors and clonotypic T-cell receptors and conclude that this relationship might account for the restricted expression of Fc receptors on T cells. PMID- 8517923 TI - Lymphocyte lifespan, immunological memory and retroviral infections. PMID- 8517924 TI - Construction and function of fusion enzymes of the human cytochrome P450scc system. AB - Type I cytochrome P450 enzyme systems are found in mitochondria and consist of three components, a flavoprotein (adrenodoxin reductase, AdRed), an iron-sulfur protein (adrenodoxin, Adx), and the cytochrome P450; Type II P450 enzymes in the endoplasmic reticulum consist of only two components, P450 reductase and the P450. Genetically engineered fusion proteins of Type II cytochromes P450 (such as steroid 17 alpha- and 21-hydroxylases) produce enzymes with increased activity. To test the consequences of constructing fusions of Type I enzymes, we built fusion proteins based on the cholesterol side-chain cleavage enzyme, P450scc. We constructed expression vectors for three fusion proteins: NH2-P450scc-AdRed-COOH, P450-AdRed-Adx, and P450scc-Adx-AdRed. The various components were assembled from cassette-like cDNA fragments modified and amplified by polymerase chain reaction (PCR), subcloned into a specially tailored vector, and linked by DNA segments encoding hydrophilic linker peptides. The final vectors were transfected into COS 1 cells, incubated with 22R-hydroxycholesterol, and assayed by the secretion of pregnenolone into the culture medium. Triple transfection of three individual vectors expressing P450scc, AdRed, and Adx yielded more pregnenolone than did transfection with P450scc alone. The P450scc-AdRed and P450scc-Adx-AdRed fusion proteins produced levels of pregnenolone similar to the control triple transfection. However, the P450scc-AdRed-Adx fusion produced substantially more pregnenolone, having an apparent Vmax of 9.1 ng of pregnenolone produced per milliliter of medium per 24 hr, compared to a Vmax of 1.7 ng/ml per day for the triple transfection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517925 TI - Murine Pax-2 protein is a sequence-specific trans-activator with expression in the genital system. AB - The murine paired box containing gene Pax-2 has been proposed to be involved in kidney and central nervous system (CNS) development. In this report, we show that expression cloning of Pax-2 cDNA allowed in vitro identification of specifically bound DNA sequences. When fused to the thymidine kinase (TK) promoter in front of reporter genes, these target sequences were able to mediate trans-activation by Pax-2 protein, thus demonstrating their in vivo function. Expression studies from adult mouse tissues revealed high levels of Pax-2 transcripts in male and female genital tracts, suggesting a second phase of Pax-2 activity. Sequence-specific DNA binding and subsequent modulation of promoter activities may constitute the molecular mechanism of Pax-2 action in specific adult tissues and during development. PMID- 8517926 TI - A novel rat serotonin receptor: primary structure, pharmacology, and expression pattern in distinct brain regions. AB - Serotonin mediates various central and peripheral functions by its ability to bind to and activate a variety of receptors that belong to four pharmacologically defined classes termed 5-HT1 to 5-HT4. Using a polymerase chain reaction-derived probe, a clone, GPRFO, was isolated from a rat brain cDNA library. This cDNA encodes a putative G protein-coupled receptor that exhibits highest similarity to receptors for biogenic amines. RNA blot analysis indicated that the corresponding gene is expressed in the diencephalon. Consistent with the RNA blot data, GPRFO mRNA has been detected by in situ hybridization in the centrolateral, central medial, and intermediodorsal thalamic nuclei. Highest amounts of GPRFO mRNA, however, have been observed in a small area, i.e., the hippocampal rudiments and the stria longitudinalis. COS-7 cells transiently transfected with the GPRFO cDNA acquire saturable high-affinity binding sites for [3H]serotonin (KD = 41 nM). The pharmacological properties of the receptor differ from those of the known serotonin receptor subtypes, suggesting that the GPRFO cDNA encodes a novel serotonin receptor that is expressed in distinct rat brain regions. PMID- 8517927 TI - Metabolic changes in osteoclasts isolated from children with fibrous dysplasia. AB - Children with fibrous dysplasia have specific areas of local bony overgrowth. The in vitro metabolism of osteoclasts obtained from involved disease areas of two patients with idiopathic monostotic fibrous dysplasia and one patient with polyostotic fibrous dysplasia were compared with osteoclasts isolated from noninvolved bone in the same individuals and normal controls. The osteoclasts from the involved regions formed similar resorption lacunae compared with osteoclasts isolated from both normal and noninvolved bone. Calcium release into the media, a function of cell-mediated resorption, was decreased in involved osteoclasts compared with osteoclasts derived from normal or noninvolved bone (p < 0.05). Osteoclasts from regions of in vivo abnormal growth exhibited normal mineral metabolism in vitro. PMID- 8517928 TI - Synthesis and regulation of complement components by human monocytes/macrophages and by acute monocytic leukemia. AB - Proteins of the complement system (C2, C3) are synthesized by human monocytes and macrophages, thus providing an important local source of these proteins in vivo which serve as a first-line host defense mechanism. In this study, we investigated the production of complement components C2, C4, and C9 by human monocytes/macrophages and by the pathologic cells of acute monocytic leukemia which represent a source of immature monocytic precursors. Human blood monocytes were collected and purified by cytapheresis and elutriation and leukemic cells by Ficoll gradient. Secretion of complement components was measured by a hemolytic assay. The evaluation of the mRNAs of the various complement components in the cells was performed by polymerase chain reaction (PCR) by adding 32P labeled deoxycytidinetriphosphate (dCTP) to the amplification step. Functional C2 was found to increase during in vitro maturation of macrophages up to the fourth week of culture. C2 mRNA was detected after amplification and increased during the maturation. Interferon-gamma (IFN-gamma) mediated a marked increase of the C2 mRNA. We found a decrease in synthesis of C4 mRNA during in vitro differentiation of human monocytes. The effect of IFN-gamma resulted in an increase in C4 mRNA. C9 mRNA was not detected although it was detected in the HepG2 hepatoma-derived cell line. Functional C2 was not detected by leukemic cells after 24 h of culture but little functional C4 was present in the cell supernatants. As they were by human monocytes and macrophages, C2 and C4 mRNAs were detected after amplification but C9 mRNAs were not detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517929 TI - Conserved motifs in rheumatoid arthritis synovial tissue T-cell receptor beta chains. AB - Rheumatoid arthritis is genetically linked to major histocompatibility complex (MHC) molecules (HLA-DR4 and related molecules) and characterized pathologically by high levels of HLA-DR expression and infiltration of proliferative of synovial tissue with CD4+ T lymphocytes. T-lymphocyte activation is driven by specific signaling through polymorphic alpha/beta T-cell receptors (TCRs) that are reactive with antigen-MHC complexes present at the sites of inflammation. We are interested in characterizing rheumatoid TCRs molecularly to ascertain potential binding surfaces for antigen+MHC in synovial tissue. Accordingly, we have recently investigated the TCR alpha and beta chain heterogeneity in a series of 10 rheumatoid synovia obtained at the time of joint surgery. The most frequently detected V beta families were V beta 12, 14, and 17, each of which was found in 80% of specimens. We report here the molecular cloning and sequence analysis of 20 cloned V beta segments amplified with a V beta 14 family-specific TCR primer, and six cloned V beta segments amplified with a V beta 17 family-specific TCR primer from four rheumatoid synovia. Comparison with the data base revealed that these sequences belonged to the closely related V beta 3, V beta 14, and V beta 17 families. Dominant clones were apparent in two of the individuals by the presence of identical V-D-J regions, suggesting an antigen-driven process. Amino acid sequence analysis revealed a conserved motif in the putative fourth hypervariable region or CDR4. Molecular modeling of this epitope suggests that charged side chains are available for binding to ligand structures (e.g., antigen, MHC, or superantigen). We suggest this epitope may play a role in the molecular pathogenesis of rheumatoid arthritis. PMID- 8517930 TI - Retrospective DNA analysis using fixed tissue specimens. AB - The recent explosion of scientific and technical knowledge in the field of molecular biology has allowed us to make important advances in our understanding of the molecular basis of many human diseases. This technology has now entered the clinical laboratory where identification of specific genetic sequences can aid in the precise diagnosis of hematologic and other malignancies, inherited diseases, specific infectious agents, and inherited predisposition to disease. In addition, it can be applied to prenatal diagnosis, paternity testing, identification of minimal residual disease following treatment, and assessment of drug sensitivity or resistance. In many cases in diagnostic pathology, the need for molecular analysis often is not realized until after a critical tissue specimen has been fixed, embedded, and examined microscopically. Thus, there is a clear need for development of techniques that would allow the retrospective study of archival tissues that have been fixed and embedded in paraffin. This review examines in depth those factors which influence the quality of the DNA available from fixed embedded tissues and discusses the usefulness of polymerase chain reaction amplification in obtaining sufficient diagnostically useful DNA from archival specimens. It is hoped that this review will aid the diagnostic pathologist interested in the application of molecular techniques in the retrospective study of fixed embedded tissues. PMID- 8517931 TI - [The management of diarrheal disease at home in some regions of Mexico]. AB - A survey was carried out between May and October, 1991 in eleven federal entities to know the correct household diarrhea case management (EMECADI). It was observed that among the 15,125 children less than five years old the punctual prevalence was of 6.4% (970 children); the incidence in the previous two weeks was 14.5% (1,605 children) and the annual incidence of diarrhea was 4.5 episodes per child per year. Among the children who presented diarrhea in the 24 hours, the following rates were observed: use of oral hydration solution, 17.1%; use of recommended homemade fluids, 63.2%; oral hydration therapy use, 63.2%; increased fluids, 29.9%; correct oral serum preparation, 60.0%; continued breast-feeding, 75.0%; continued feeding, 59.8%; adequate knowledge about seeking care, 12.5%, and drugs use, 53.2%. The reference and nutritional components should improved. PMID- 8517932 TI - [The effect of phenobarbital on the severity of intraventricular hemorrhage]. AB - During an eight-months period, we studied every newborns under 34 gestation weeks who needed mechanical ventilation (MV) from the moment they were born and whom had an ultrasonogram without intraventricular hemorrhage in the first six hours after birth. Patient were separated in two groups: the first, a group of 30 patients received phenobarbital 20 mg/kg IV in the first 6 hours of life and then 2.5 mg/kg, I.V., every 12 hours for the next five days. Blood levels were measured 24 and 96 hours after the initial dose was given. The second group of 30 patients was not treated with phenobarbital. In both groups a brain ultrasonogram was made every 48 hours until 15 days of life. There were no difference in weight, gestational age, Apgar score, way of birth, initial diagnosis, incidence of pneumothorax, mortality and days with MV between the two groups. During the first three days were measured blood glucose, blood pressure, mean airway pressure, PCO2, PO2 and found no significant difference between both groups. The blood pH showed statistically significant difference, with better values at 48-72 hours in the group treated with phenobarbital. The global incidence of intraventricular hemorrhage was 16 (53%) in the group treated and 14 (46%) in the not treated, this difference was not statistically significant. The degree of hemorrhage, found was: I and II degree, eleven (69%) in the treated group and four (28%), in the control group; III and IV degree five (31%), in the treated group and ten (71%), in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517933 TI - [The nutritional status of the child entering the Nuevo Hospital Civil de Guadalajara]. AB - With the purpose to evaluate the nutritional status of children hospitalized in the Nuevo Hospital Civil de Guadalajara, they were included 278 subjects that entered in the infant, preschool, schoolchildren and infectious disease clinical ward of the Division of Pediatrics. There were chosen two subjects every day during one year. It was obtained information about family and sociodemographic background. In addition, there were undertaken anthropometric measurements; weight/age, weight/height and height/age indices were also calculated. It was obtained the parameters of median, percentiles and Z-score. Undernutrition was determined by the Gomez and Waterlow classifications. Is was also compared the reference pattern of Ramos-Galvan and National Center for Health Statistics (NCHS). Blood was drawn for total protein and hemoglobin. Mean of height/age was 95.74% (NCHS), weight/age 84.04% and weight/height 89.7%. It was not difference on weight/age between Ramos-Galvan and NCHS. Weight/height and height/age had little difference. The median system identified more cases with deficit than Z score, which seems to be more specific and conservative. There is a high prevalence of acute and chronic malnutrition identified with the median system, and maybe reflects the poor quality of life and major morbidity in this population. PMID- 8517934 TI - [Experience in the use of central venous catheterization via subclavian puncture in a pediatric hospital]. AB - OBJECTIVE: To assess the frequency and type of complications during central venous catheter installation by subclavian puncture, and during its use in children admitted to an ICU. PATIENTS AND METHODS: Patients from one month to 15 years of age, admitted to the Intensive Care Unit of the Hospital de Pediatria Centro Medico Nacional, Siglo XXI, who underwent a percutaneous infraclavicular subclavian puncture for central venous catheter complications were included. Clinical features, diagnosis, complications and indications for the procedure were registered. RESULTS: 92 patients and 102 subclavian punctures were included for analysis. Effectively index was 88.3%. Main diagnosis was infectious diseases in 29.4% and neoplasia in 22.5%. Hemodynamic monitoring was the more frequent indication for the procedure (44%). Of the catheter 45% were successfully installed at first intent. The complication in the installation appear in 11.7%. Was arterial subclavian puncture (6.8%), hematoma (2.9%), without hemodynamic deterioration no any case. The mean time of permanence was 8.8 days. The late complications was present in average 7.3 days, in 18.6% of the cases. Predominance infection in entrance place of catheter. CONCLUSIONS: Installation of venous central catheter by subclavian puncture prove a great utility in our patients, with a few complications and a high effectively. For experimental personal the central venous catheterization by subclavian puncture in pediatric patients to be importance in the first place in critical ill children. PMID- 8517935 TI - [The rapid diagnosis of rubella and measles by the dot immunoassay method]. AB - A procedure is described for the routine laboratory identification of IgM or/and IgG antibodies to measles and rubella simultaneously. A rapid dot-immunobinding assay on nitrocellulose was compared with ELISA systems. 58 serum samples from patients with an exanthematous disease and 15 serum negative samples for both virus were studied. The type of antibody found in all samples was variable and was always related to the presence of immunity in each individual. However, all known negative samples were negative. When results were compared with commercially available ELISA systems or reference laboratories, we found an excellent correlationship including titers. We concluded that the dot immunobinding assay is a rapid, specific, sensitive, reproducible and economic test that can be used simultaneously for identification of several antigens. PMID- 8517936 TI - [Acute gastric distension due to sepsis in a newborn infant]. AB - The acute distention of stomach in the newborn is conditional by metabolic alterations like hypocalcemia or by septic states. We present the case of a newborn with antecedents of membrane rupture for 12 hours obtained by cesarean procedure, of 38 weeks by Capurro, score without perinatal asphyxia and 3320 g of birth weight, which evolutioned with respiratory distress and its first exams showed leukopenia, low platelet count and the cerebrospinal fluid showed 390 cells with polymorphonuclear predominium considering the diagnosis of neonatal sepsis and meningitis. At the second day he presented abdominal distention secondary to gastric camera dilatation, were made a laparotomy to descart congenital obstruction and only found gastric distention. In all newborn with acute gastric distention its important for first instance descart congenital intestinal obstruction and is on sidered this entity by exclusion. We recommend in this patients sepsis worshop. The treatment is drainage by orogastric tube and antibiotics. The prognosis is good once upon treating the basic problem. PMID- 8517937 TI - [The congenital absence of the femur. A report of 2 cases]. AB - We present two patients with congenital femoral absence, in six year period, in two hospitals of Minatitlan, Veracruz, Mexico. The first case is a six-year-old male. He begin to walk at four year old. The second case is a twelve-month female, who the walk is not started. Furthermore, she have another muscle skeletal malformations. None of the have received surgical treatment. We give information about of several classifications of femoral congenital malformations. PMID- 8517938 TI - [The impact of Haemophilus influenzae infections on Mexican children]. AB - A review of Haemophilus influenzae (Hi) infections in Mexico over the past 32 years was conducted. The proportion of Hi isolates in relation to positive cultures for distinct diseases was distributed as follows for meningitis (9-69%) and for pneumonia with empyema (6-28%). There was no difference in the proportion of Hi isolation between under developed countries and the United States. In other diseases such as septic arthritis, epiglottitis, acute otitis media, acute maxillary sinusitis and in the nasopharyngeal carrier state, the information was too limited. The incidence of Hib invasive disease has been almost eliminated in some areas of the world related to the use of Hib conjugated vaccine. It is imperative for the practitioner to be aware of the advantages of Hib vaccine in infancy. PMID- 8517939 TI - [Food allergy]. AB - We are exposed to a large amount of potentially antigenic substances when we take aliments. Normally the mechanic, enzymatic and immunitary functions avoid the development of deleterious phenomena. Thus, when these mechanisms fail intolerance, idiosyncrasy or allergic reaction could be presented to the diet components. The adverse reactions to the aliments are present in one to three percent of the general population, while this occurs in the eight percent of the children under three years old. The clinical manifestations may comprise from abdominal pain pictures to anaphylactic shock. The symptomatology depends on age of the patient and the amount and kind of ingested food. The diagnosis must be establish on bases of careful anamnesis and physical examination. To confirm the diagnosis cutaneous test for immediate hypersensibility and the determination of specific IgE antibodies (RAST, ELISA) are used. The basic treatment consists in the withdrawal of the causative aliment and not on non-proper diets for the patient. PMID- 8517940 TI - [An oral delayed-action formulation for release in the colon]. PMID- 8517941 TI - Adjustment of young adults with mental retardation in community settings: comparison of parametric and nonparametric statistical techniques. AB - The impact of four different statistical techniques on the interpretive process using data obtained from young adults with mental retardation in applied settings was evaluated. Our hypothesis was that no difference exists across levels of mental retardation for four dependent variables, jointly or separately, using (a) parametric multivariate analysis of variance, (b) nonparametric multivariate analysis of variance, (c) multiple nonparametric analyses of variance, and (d) multinomial logistic regression. The pattern of significance remained the same across the three classical and quasi-classical designs. Substantive differences were found using the fourth technique, multinomial logistic regression. The four techniques were compared using interpretational as well as statistical criteria. PMID- 8517942 TI - Personal characteristics and competence of people with mental retardation living in foster homes and small group homes. AB - In this 1986-1987 study, the demographic and diagnostic characteristics, problem behaviors, self-care skills, community living skills, domestic expectations, and program goals for personal competence of 336 persons with mental retardation living in a national sample of 181 foster care and small group care settings with 6 or fewer residents was assessed. The findings indicated relatively more severe cognitive impairment among persons in small ICFs-MR, less severe cognitive impairment and fewer functional limitations among non-ICF-MR group home residents, and more functional limitations among residents in foster homes. Neighborhood integration was relatively high for foster home residents, but there were fewer expectations for their development of home and community living skills. Implications for future research and program development in small, community-based residential settings were discussed. PMID- 8517943 TI - Movement preparation in adults with and without Down syndrome. AB - This study was designed to determine whether adults with mental retardation, with and without Down syndrome, display flexibility in the preparation of limb movements. A four-alternative target-aiming task involving movements with either the right or left hand to near or far targets was employed. Prior information about the movement to be made was manipulated by precuing specific features. Although reaction times and movement times were longer for subjects with than for those without mental retardation, the pattern of results was similar. Specifically, both retarded groups were able to use advance information to reduce movement preparation time. Moreover, information about movement distance was useful to subjects whether or not hand was precued. This finding indicates that the individuals with mental retardation were not limited by a fixed-order movement preparation process. PMID- 8517944 TI - Analysis of behavior state conditions and associated environmental variables among students with profound handicaps. AB - State conditions in combination with environmental events and factors significantly affect the level of alertness and responsiveness among students with profound and multiple handicaps. State conditions and environmental variables over a continuous, 5-hour period for each of 25 students in classroom settings were measured. Data were assessed using transitional probability, time series, and correspondence analysis procedures. Results showed the presence of state sequence patterns, short state change periods, and a relatively small amount of association between specific behavior states and the environmental factors and events measured in the study. PMID- 8517945 TI - Beneficial effects of exercise on aerobic capacity and body composition in adults with Prader-Willi syndrome. AB - Adults with Prader Willi syndrome were subdivided into an experimental group (n = 6) and a control group (n = 5) to determine the effects of an aerobic exercise program. Their resting heart rate, aerobic capacity, body fat percentage, body weight, and somatotype were determined. Participants in a 6-month walking program showed statistically significant differences in all variables measuring aerobic capacity and a significant variation in weight loss over the 6-month program compared to the control group. PMID- 8517946 TI - Self-injurious behavior within the menstrual cycle of women with mental retardation. AB - There are no reports of an association between the menstrual cycle and self injurious behavior (SIB) in the mentally retarded population. However, the endogenous opiate system has been implicated in both menstrual cycling and SIB. Catamenial and behavioral records of 9 women with mental retardation who exhibited SIB were analyzed for 6 months to determine the association between phases of the menstrual cycle and rates of SIB. Menstrual cycles were divided into four phases: (a) menses and early follicular phase, (b) late follicular phase, (c) early luteal phase, and (d) late luteal or premenstrual phase. Analysis showed that the highest frequency of SIB occurred in the first two phases: 43.5% during early follicular phase and 47.3% in the late follicular phase. Pairwise t and binomial expansion tests confirmed that SIB was cyclic across the menstrual cycle with Phase 1 > Phase 3, Phase 1 > Phase 4, Phase 2 > Phase 3, and Phase 2 > Phase 4. Seven of the 9 women were cyclers and manifested identical phase/SIB relations. The cyclical character of SIB may relate to changing peripheral and central endorphin and pain threshold during the cycle. PMID- 8517947 TI - Social skills and classroom behavior among adolescents with mild mental retardation. AB - Relations among self-reported social skills, teacher ratings of classroom behavior, and direct observations of social interactions among 87 adolescents with mild mental retardation were investigated and variables predicting the students' task orientation identified. Three information sources were employed. Results demonstrated that the four domains of social skills were related to the students' task orientation. The regression analysis revealed that students who were characterized by better social skills and fewer occurrences of hyperactivity and behavioral difficulties were viewed by teachers as evidencing more compliant and task-oriented behavior, implying their better ability to benefit from the special curriculum. The three sources of information validated one another and added information to the conceptualization and appraisal of social and academic competence among students with mental retardation. PMID- 8517948 TI - Pupils with mild mental retardation in regular Swedish schools: prevalence, objective characteristics, and subjective evaluations. AB - Pupils in regular Swedish schools who met the psychometric criterion of mental retardation were identified and described. Using a national longitudinal data set, we compared a group of 13-year-old pupils (N = 116) not officially classified as having mental retardation to their peers without mental retardation across measures of school achievement, social background, self-evaluations of school experiences, and upper secondary school education. The results showed that the former group was low-achieving and had poor self-evaluations; however, some pupils in the general population shared these characteristics. PMID- 8517949 TI - Warm body, cold heart surgery. Clinical experience in 2817 patients. AB - Systemic hypothermia is used almost universally in cardiac surgery. Since 1987, 2817 patients have had normothermic cardiopulmonary bypass (NCPB, "warm body", bladder temperature 36 degrees C) with cold blood cardioplegic arrest ("cold heart", 8 degrees-14 degrees C) during open heart surgery. No patients were denied this technique regardless of age, condition or severity of surgery. Clinical Characteristics in Patients: Age range: 16-84 years, mean 66; male/female ratio 3:1; pump time (min) 24-183, mean 91; cross-clamp time (min) 15 148, mean 68; types of surgery: coronary artery bypass (n = 2214), valvular (n = 489) and miscellaneous (aneurysms, tumors, arrhythmias, congenital, etc) (n = 114). One thousand and sixty-nine (1069) patients had urgent coronary artery bypass grafting (CABG). The ejection fraction was less than 0.40 in 843 patients (30%). The thirty-day operative mortality for the entire group was 1.7% (48/2817 patients): CABG = 1% (23/2214 patients), valvular = 3% (15/489 patients) and miscellaneous 9% (10/114 patients). Postoperative complications were: perioperative myocardial infarction (34 patients) = 1.2%, postoperative bleeding requiring reexploration (37 patients) = 1.3%, stroke (27 patients) = 1%, and mediastinal infection (21 patients) = 0.7%. During NCPB (WARM) systemic vascular resistance was extremely low, cardiac output was high and it was easier to wean patients from the pump. No intraaortic balloon pump was used during this period. Pulmonary complications and coagulopathy were extremely rare. These results provide reassurance that NCPB (WARM) in combination with cold cardioplegic arrest provides excellent myocardial and total body protection during cardiac surgery and is particularly suitable for high-risk patients. PMID- 8517950 TI - Relationship between hemodynamics and blood volume changes after cardiopulmonary bypass during coronary artery bypass grafting. AB - The blood volume and central hemodynamics were assessed in 22 patients undergoing coronary artery bypass grafting before and after cardiopulmonary bypass. Patients were divided into two groups according to their blood volume after cardiopulmonary bypass. In group A (n = 10) the patients were hypovolemic and in group B (n = 12) the patients were hypervolemic after cardiopulmonary bypass. At the same time the mean plasma volume did not change significantly in group A and increased in group B. Hypovolemia in group A was accompanied by a significantly lower cardiac index and oxygen delivery index than in group B. There was a correlation between the changes in cardiac index and changes in total blood volume (r = 0.57; P < 0.01). Patients in neither group suffered from hypoxia. We conclude that extreme hemodilution after cardiopulmonary bypass must be normovolemic, and the pulmonary capillary wedge pressure or right atrial pressure as a guide for blood volume evaluation after termination of cardiopulmonary bypass may be misleading. PMID- 8517951 TI - The internal mammary artery 'string phenomenon'. Analysis of 10 cases. AB - The internal mammary artery (IMA) string sign has been described as a narrowing of IMA grafts in the late course after coronary artery bypass grafting. It has been assumed that this phenomenon was due to competitive flow in grafts connected to only mildly stenosed coronary arteries. We analyzed 10 cases of IMA string sign operated on between March 1988 and June 1991. Bilateral IMA was used in six cases and unilateral IMA in four. The mean interval between operation and reangiography was 14 +/- 11 months. String sign of the whole length of the IMA was detected in nine cases, and of the distal part between two sequential anastomoses in one. In all cases, the stenosis of the vessel bypassed with the narrowed graft proved to be only mild (50% or less) at reangiography. In all six cases with bilateral IMA grafts, the contralateral IMA was widely patent. These were all connected to highly stenosed or occluded coronary arteries. With respect to this observation, there is a high index of suspicion that the string phenomenon occurs due to competitive flow in only mildly stenosed coronary arteries. We decided, for our strategy in coronary artery surgery, still to aim at complete revascularization using IMAs as much as possible, but to avoid connecting IMA grafts to only mildly or moderately stenosed coronary arteries. PMID- 8517952 TI - Diltiazem provides anti-ischemic and anti-arrhythmic protection in patients undergoing coronary bypass grafting. AB - In 91 patients undergoing elective coronary bypass grafting, the anti-ischemic and anti-arrhythmic efficacy of a 24-hour infusion of either the calcium antagonist diltiazem (0.1 mg/kg per h, n = 44) or nitroglycerin (1 micrograms/kg per min, n = 47) were compared. Myocardial ischemia was diagnosed by Holter monitoring and the repeated assessment of 12-lead ECG and serum enzyme levels and defined as a transient ischemic event, transient coronary spasm or myocardial infarction. The two groups did not differ with respect to preoperative and operative data. Postoperatively, the average heart rate and pulse pressure rate were significantly lower in the diltiazem group. The incidence of postoperative atrial fibrillation (4.5 vs 19.1%, P < 0.01), transient coronary spasm (2.3 vs 11.4%, P < 0.05) and myocardial infarction (4.5 vs 8.5%, not significant) and the frequency of ventricular premature couplets/h (12.1 +/- 4.5 vs 18.1 +/- 5.1, P < 0.05) and ventricular runs/h (2.5 +/- 0.8 vs 6.5 +/- 2.8, P < 0.05) were lower in the diltiazem as compared to the nitroglycerin group. In addition, diltiazem treated patients had significantly lower postoperative peak values of creatine kinase-MB (19.3 +/- 11.6 vs 29.3 +/- 20.6, P < 0.05). In conclusion, perioperative infusion of diltiazem is effective in reducing the incidence and extent of arrhythmias and myocardial ischemia in patients undergoing elective coronary bypass grafting as compared to patients receiving nitroglycerin. PMID- 8517953 TI - Results of subtotal pericardiectomy for constrictive pericarditis. AB - The operative approach to constrictive pericarditis still remains a surgical challenge. Subtotal pericardiectomy through median sternotomy was analyzed retrospectively in a series of 84 patients operated on for chronic constrictive pericarditis at our institution between 1979 and 1989. The mean duration of symptoms prior to diagnosis was 20 +/- 6 months (1-264 months). Preoperatively, 72% of patients were in NYHA class III or IV, presented signs of right cardiac failure (88%) or anasarca (18%). Chest X-ray showed pericardial calcifications in 40% of the patients. Echocardiography revealed pericardial thickening in 62%. Among 62 patients in whom cardiac catheterization was performed, a characteristic dip-and-plateau was found in 47 patients (76%). A specific etiologic factor was identified in only 37 patients: tuberculosis (12%), recurrent acute pericarditis (9%), hemopericardium (9%), radiotherapy (5%), previous cardiac surgery (4%), bacterial infection (2%), myocardial infarction (2%) and connective tissue disease (2%). In 47 patients (55%), the constrictive pericarditis remained idiopathic. In seven patients we performed a redo-operation for previous incomplete pericardiectomy. Subtotal pericardiectomy (from phrenic nerve to phrenic nerve) was performed in 75 patients. A palliative procedure consisting of pericardial "meshing" was performed in nine patients due to an unsatisfactory cleavage plane. Cardiopulmonary bypass was used in four patients for coexistent cardiac lesions. The operative mortality was 2.3% (two patients: septicemia and pulmonary embolism). Seven patients (8.2%) developed early on-lethal complications. The probability of survival for patients discharged for the hospital was 94% at 3 years and 87% at 7 years. There were four late deaths and no reoperation for recurrent constriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517954 TI - The impact of early postoperative cyclosporine serum levels on the incidence of cardiac allograft rejection. AB - The introduction of cyclosporine A (CyA) into the immunosuppressive therapy has significantly improved the results of heart transplantation (HTX). Its nephrotoxicity and hepatotoxicity, however, often limit the perioperative and postoperative use of this drug. The purpose of this retrospective study was to evaluate the effect of early postoperative CyA blood levels on the incidence of early as well as late cardiac rejection and patients' survival. Between October 1985 and June 1991, HTX was performed in 311 patients. Standard immunosuppression consisted of azathioprine (1-2 mg/kg), prednisolone (0.5 to 0.1 mg/kg) and CyA. Rabbit-antithymocyte-globulin (RATG - 1.5 mg/kg) was administered for the first 4 days postoperatively. Moderate rejection was treated with 3 x 500 mg methylprednisolone, severe rejection with RATG (1.5 mg/kg three times a day). Patients were excluded from this study because of a positive cross-matching, early death unrelated to rejection or alternate forms of immunosuppression (n = 111). Follow-up was complete in 200 patients (mean age 44 +/- 11; 18 female, 182 male; 204,233 patient days) with a total of 5380 biopsies. The cohort was divided into group I (no CyA for day 0 to 2; n = 108) and group II (CyA during day 0 to 2; n = 92) according to the onset of CyA therapy. In 101 patients (group A) the mean CyA blood level was less than 150 ng/ml from day 0 to 14 and in 99 patients more than 150 ng/ml (group B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517955 TI - Valve-related events and valve-related mortality in 340 mitral valve repairs. A late phase follow-up study. AB - To assess the early and late valve-related events, 340 consecutive patients undergoing mitral valve repair from 1969 to 1988 were evaluated. Follow-up was complete, with a mean of 7.5% years and range from 2 to 22 years (cumulative 2456 patient-years). There were 221 (65%) female patients. Rheumatic valvular disease was present in 246 (68%) patients. The remaining patients had ischemic or congenital valve disease, floppy valve or infective endocarditis. At surgery, 47% of the patients had pure mitral incompetence, 43% had mixed mitral stenosis and incompetence and 10% had predominant mitral stenosis. Seventy-three percent of the patients were in functional class III or IV. Twelve percent had had prior heart surgery. Concomitant valve procedures including coronary revascularization were performed in 62.3%. There were 23 hospital deaths (6.8%) but only 3 of these (0.8%) were valve-related in patients who died at reoperation for valve repair failure. There were 4 other early repair failures who survived early reoperation. Of the 317 hospital survivors, there were 127 late deaths, and an actuarial survival of 44 +/- 3.7% (70% CL) at 14 years. Of these, 13 were valve-related or 0.5% patient-year. Late events included thromboembolism (TE) 1% patient-year, anticoagulant bleeding 0.4% patient-year, infective endocarditis (IE) 0.2% patient-year and late reoperation for mitral valve repair failure in 63 patients or 2.8% patient-year. At the late follow-up, 88% of the hospital survivors were in functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517956 TI - Surgical treatment of a large eventration of the left diaphragm. AB - Total eventration of the left diaphragm is a rare condition in adults. It is now generally accepted that surgery is indicated only in cases of distinct complaints involving abdominal or thoracic organs which can be related to this pathological condition. The accepted routine surgical procedure for treatment of the eventration is plication of the diaphragm without incision or excision of the pathologically changed part of the diaphragm. In rare cases, reinforcement of the very thin membrane with some foreign material may be necessary. We describe an adult patient with extensive eventration and severe symptoms in whom we used a special technique for restoration of the diaphragm with very good results. PMID- 8517957 TI - Complete occlusion of all three main coronary arteries, with survival dependent on two septal arteries. AB - A 68-year-old Asian gentleman presented with limiting angina pectoris following myocardial infarction. Coronary angiography demonstrated complete occlusion of the left anterior descending artery after the first septal, the proximal right coronary artery and also the proximal part of the circumflex. The myocardial blood supply was wholly dependent on two septal arteries. PMID- 8517958 TI - Histology of arterial conduits as a predictor of their long-term patency as coronary bypass conduits. PMID- 8517959 TI - The procedure of choice for double lung transplantation? PMID- 8517960 TI - [Cerebellar medulloblastoma in childhood: supratentorial metastasis]. AB - Reports on supratentorial metastases of medulloblastoma are infrequent. Computed tomography has increased the possibilities of detecting then in a silent clinical phase. Five children with supratentorial metastasis of medulloblastoma were retrospectively reviewed. Diagnosis was established by cranial CT between three and sixty months following treatment of the tumor. Dissemination through the ventricular system was found in all the cases. Other lesions were found in the transition zone between the white and grey matter (2/5) and the left frontal lobe (1/5). The routes of dissemination are discussed. Early diagnosis of supratentorial metastasis of medulloblastoma require periodic cranial CT or magnetic resonance imaging (MRI), at least during the first years after diagnosis and treatment of the primary tumor. PMID- 8517961 TI - [Anticardiolipin antibodies and their association with the brain]. AB - With the aim of establishing whether there is a relationship between anticardiolipin antibodies and migraine a prospective single blind study was performed. One hundred patients were analyzed, 50 without migraine [22 men (44%) and 28 women (56%)] and 50 with migraine 20 men (40%) and 30 women (60%). The mean age of the control group was 28.3 years (range 15 to 39) and that of the group with migraine was 26.5 years (range 14 to 40). The anticardiolipin antibodies were positive in two cases of each group. This study demonstrates that no association exists between migraine and the presence of anticardiolipin antibodies. Patients with migraine have the same incidence of anticardiolipin antibodies as the general population (4%). PMID- 8517962 TI - [Pathogenesis of Parkinson's disease: a possibility of oxidation]. PMID- 8517963 TI - [Permanent hemispheric pain syndrome due to traumatic cortico-subcortical lesions in the left hemisphere]. AB - Pain due to cortical-subcortical lesions may be paroxystic or permanent. The latter may be strictly similar to that derived from the selective involvement of the thalamic ventroposterior nucleus. We report a 21 year-old right handed patient who in a cranial-encephalic injury had a counter-stroke lesion of the left parietal-temporal-frontal region, demonstrated by magnetic resonance imaging (MRI), and who remained in coma for 2 weeks. At 6 weeks the patients began to have continuous burning algias in the right hemisome with hyperpathy, allodynia, etc., with exacerbations. Treatment attempted to elevate the levels of brain serotonin was followed by partial improvement. Likewise, the patient presented certain aphasic disturbances and showed different coordination synkinesis, etc., of the right side. The somato-sensitive evoked potentials (PE) were normal. A review of the literature is undertaken emphasizing the rarity with which algic pictures by cortical-subcortical lesions appear in lesions of the dominant hemisphere. Special emphasis is made in the concept of "deafferentation", particularly developed during the last decade (Albe-Fessard, Tasker, Leijon, Boivie). Following the suggestions of Albe-Fessard, the possibility of a central algogenic mechanism by "retrograde" deafferentation (interference in the thalamic cortical loops) of the median thalamus (unspecific nuclei or of diffuse projection) as a consequence of the cortical-subcortical lesion (of an outstanding form, probably of the parietal operculum) is suggested. PMID- 8517964 TI - [Spinal epidural abscesses. Conservative treatment. Three cases]. AB - Spinal epidural abscesses (SEA) are an infrequent disease which should be suspected in patients with spinal and/or radicular pain, neurologic deficits and fever. We present 3 patients with SEA (two lumbar and one dorsal) who recovered following exclusively antibiotic treatment. The complete disappearance of the abscess was proven by magnetic resonance. Patients with SEA and discrete, stable deficits and with known germs, are susceptible to medical and not surgical treatment. PMID- 8517965 TI - [On the editorial "The sunset of psychiatry"]. PMID- 8517966 TI - [The rebirth of psychiatry]. PMID- 8517967 TI - [On "the sunset of psychiatry" (I). Structuralism and theology]. PMID- 8517968 TI - [On "The sunset of psychiatry" (II). In reference to questionable claims of psychiatry]. PMID- 8517969 TI - [Arterial hypertension in the elderly and renal function]. AB - STUDY OBJECTIVE: to evaluate the effects of antihypertensive treatment on renal function, in an elderly population of 29 patients with arterial hypertension. DESIGN: retrospective study of the first six months follow-up. SETTING: outpatients clinic of arterial hypertension in the elderly at a central hospital. PATIENTS AND METHODS: twenty nine elderly (> or = 65 years old) patients with a mean age of 71.8 +/- 5.6 years, with arterial hypertension (> or = 160/95 mmHg) submitted to antihypertensive treatment. Fourteen males and fifteen females. The systolic, diastolic and mean blood pressure was determined with a DINAMAP 1846, previously and at the first, third and sixth month of antihypertensive treatment (diuretic, calcium antagonists and angiotensin converting enzyme inhibitors). The serum creatinine was evaluated in the beginning of treatment and six months later. Means (+/- standard deviation) were compared with Student's t-test (statistically significant findings < 0.05). MEASUREMENTS AND RESULTS: the initial mean arterial pressure was 127.0 +/- 17 mmHg; with the antihypertensive treatment, was 119.1 +/- 16 mmHg in the first month, 114.4 +/- 12 mmHg in the third and 117.6 +/- 12 mmHg in the sixth month. The serum creatinine was 1.26 +/- 0.75 mg/dl in the beginning of the study and the final result was 1.30 +/- 0.74 mg/dl (p-NS). CONCLUSIONS: the antihypertensive treatment was effective in reducing the blood pressure, without a significant increase in serum creatinine. PMID- 8517970 TI - [A case of "fluctuating" arterial hypertension]. AB - A case of arterial hypertension with clinical and laboratory findings typical of renovascular hypertension is presented. The situation normalized after prolonged rest and exacerbated on orthostatism. Directed study demonstrated a giant pseudo cyst of pancreas that caused the situation which normalized after elective pancreatectomy. A brief comment and a review of literature is presented. PMID- 8517972 TI - [We are entering a new year of publication of the Revista Portuguesa de Cardiologia]. PMID- 8517971 TI - [Primary hyperaldosteronism. A report of 2 clinical cases]. AB - We describe two clinical cases of primary hyperaldosteronism caused by adrenal adenoma (Conn's syndrome) with very different forms of clinical presentation. Some theoretical considerations about diagnosis and treatment of the disease are made. PMID- 8517973 TI - [The clinical significance of mitral insufficiency detected by Doppler echocardiography in acute myocardial infarct]. AB - OBJECTIVE: To assess the clinical significance of mitral regurgitation (MR) diagnosed by pulsed Echo-Doppler in patients with acute myocardial infarction (AMI). SETTING: Admission in a coronary care unit and a mean follow-up of 12 months. PATIENTS: Seventy nine patients admitted in a coronary care unit, and 66 patients were followed-up for 12 months (mean). METHODS: Pulsed Echo-Doppler were performed within three days after admission and the presence of MR was analyzed by apical four and two chamber views. RESULTS: There were 62 males and 17 females (mean age: 61.4 +/- 10.8 (31-84) years). The location of AMI was: anterior--40, inferior--30, non-Q wave--6, indeterminate--2 and combined--1. Killip classes were: class I--50, class II--20, class III--7 and class IV--2. 17 patients had a previous AMI. The in-hospital mortality was 9 patients (12%) and the post hospital mortality was 3 patients (4.5%). MR was detected in 24 patients (30%) in whom 14 (58%) had no murmur of MR previously auscultated. MR was considered moderate in 10 patients and mild in the others 14 patients. There were no significant statistical differences in the frequency of MR in relation to AMI location: anterior 57%, inferior 40% (chi 2 = 0.71, NS); to the presence of a previous AMI: 47% vs 26% (chi 2 = 1.93, NS); to age (61 vs 62 years). The patients with MR suffered a more serious degree of heart failure (class III + class IV): 29% vs 4% (chi 2 = 8.41, p < 0.005); higher hospital mortality: 29% vs 4% (chi 2 = 8.41, p < 0.005); and higher one year mortality: 37.5% vs 5.5% (chi 2 = 10.9, p < 0.001). CONCLUSION: The presence of MR had no relationship with AMI location, the presence of a previous AMI or patients age. The patients with MR had a more serious degree of heart failure, higher hospital and one year mortality. The presence of MR detected by pulsed Echo-Doppler is a sign of bad prognosis although being auscultatory silent in a half of patients. PMID- 8517974 TI - Good clinical trials and good clinical practice. PMID- 8517975 TI - [Patron saints in the logistics of care at Lisbon hospitals]. PMID- 8517976 TI - [Dilated myocardiopathies: the relationship between the degree of cardiac dysfunction and ventricular arrhythmias. A clinical follow-up]. AB - STUDY OBJECTIVE: Characterization of the arrhythmic profile of idiopathic dilated cardiomyopathy (DMC); Evaluation of the relation of complex ventricular ectopy and cardiac dysfunction; Clinical outcome. PATIENTS: We studied 20 patients (P) with idiopathic DCM, 15 males P and 5 female P, mean age 51.3 +/- 17.4 years (between 17 and 75 years). MATERIAL AND METHODS: 24-hours Holter study and left cardiac catheterization with ventriculography were performed. Patients were followed at the consults. RESULTS: We detected in the Holter study the presence of ventricular ectopy in 19 P (95%). Nine P had complex ventricular arrhythmias (45%), 10 P had simple ventricular arrhythmias (50%) and 1 P had no ventricular arrhythmia (5%). The mean left ventricular ejection fraction was 28.6 +/- 14.1% (12 to 44%). Two groups were defined based on the severity of left ventricular dysfunction: Group I with 12 P and Group II with 8 P. In Group I, 8 P had complex ventricular ectopy and, in Group II, 1 P had complex ventricular ectopy (p < 0.05). Comparing mean left ventricular ejection fraction in the two groups of arrhythmias (simple and complex), 33.9 +/- 12.5% and 22.1 +/- 13.8%, we found out a statistically significant difference (p < 0.05). After an eight to thirty six months of follow-up, a greater number of cardiac events (mortality, transplant) were detected in the groups of complex arrhythmia and of more severe cardiac dysfunction. CONCLUSIONS: We conclude that there is a high frequency of ventricular arrhythmias in this group of patients with idiopathic DCM. Complex ventricular arrhythmias were more frequently associated to more severe left ventricular dysfunction. The number of cardiac events at follow-up was higher in patients with complex ventricular arrhythmias and in those with more depressed cardiac function. PMID- 8517977 TI - [Cardiological changes in candidates for sports]. AB - OBJECTIVES: To evaluate the incidence and the clinical significance of the cardiologic abnormalities detected in candidates to competitive sports. DESIGN: Retrospective study of candidates to competitive sports who were evaluated for heart fitness. SETTING: Out patient cardiologic clinic in a Center of Sports Medicine in Lisbon. PATIENTS AND METHODS: 420 subjects out of a population of 6795 were followed up for one year. They underwent clinical evaluation with ECHO (M mode, 2D, Doppler), 24 hours Holter monitoring and Exercise Tests as indicated for decision concerning fitness and adequacy for the practice of competitive sports. RESULTS: Main reason for observation was the assessment of the significance of cardiac murmur (265; 6.3%). 14 cases of organic heart disease were diagnosed: 9 bicuspid aortic valves (2 with systolic gradient over 40 mmHg), 2 with atrial septal defects, 2 significant mitral valve prolapse and 1 ventricular septal defect. 86 patients were evaluated because of ECG abnormalities; 26 out of these presented ventricular ectopic beats, 6 had delayed AV conduction (PQ > 0.24 sec), 44 developed non specific STT changes and 16 a pre excitation (WPW) tracing. Holter studies demonstrated 8 cases of complex ventricular premature beats and one case of paroxysmal atrial tachycardia. Arterial hypertension was the reason for evaluation of 20 athletes, 5 of whom were considered unfit due to hypertensive response to effort and/or systemic involvement. CONCLUSIONS: The evaluation of heart murmurs was the principal reason to evaluate candidates to the practice of sports. The large majority were considered innocent murmurs. Ventricular premature beats, non specific repolarization changes and pre-excitation (WPW) were the predominant electrocardiographic abnormalities. There was a remarkably low incidence of organic heart disease in the latter group. The most common reasons to declare unfitness for competitive sports practice were repetitive ventricular ectopic beats and arterial hypertension. PMID- 8517978 TI - [The heart-lung transplant. Initial clinical experience]. AB - PURPOSE: To assess this initial clinical experience with heart-lung transplantation in Brazil. METHODS: Four patients underwent heart-lung transplantation from December 1988 to March 1990, one patient with cardiomyopathy and high pulmonary resistance, two patients with primary pulmonary hypertension and another with pulmonary silicosis. The heart lung blocks were harvested from the donor using cardiopulmonary bypass and deep hypothermia. They were transplanted to the recipient by anastomosing the trachea, right atrium or venae cavae, and the ascending aorta. RESULTS: The second patient died on the 5th postoperative day due to respiratory insufficiency with consequent brain lesions. The first and third patients had survived nine months and 42 days respectively. The 4th patients is asymptomatic eight months after the operation. The main complications were bleeding in two patients, acute pulmonary rejection in three of them and obliterans bronchiolitis in one patients. CONCLUSION: The heart lung transplantation is a challenging procedure which results are progressively improving with the development of better surgical technique and clinical concepts. PMID- 8517979 TI - [Development of the background activity of EEG in children with epilepsy; comparison with normal children]. AB - We investigated the development of the background activity of EEGs in 150 children with epilepsy by means of computerized power spectral analysis, using Fourier transformation by O1 Twenty-seven cases with idiopathic generalized epilepsy (IGE), 30 cases with idiopathic partial epilepsy (IPE), 60 cases with symptomatic partial epilepsy (SPE), 33 cases with cryptogenic partial epilepsy (CPE) and 48 normal children were studied. The records with paroxysmal activity at 01 were excluded in this study. In normal children, total, delta and theta powers showed a significant inverse correlation with age, but alpha-2 and beta-2 powers showed a significant positive correlation with age. In children with epilepsy, there were significant increases of delta and theta powers and a decrease of alpha-2 power compared with normal children. The development of the EEGs was different among the patients with various types of the epileptic syndrome. It was suggested that age, prognosis and anticonvulsants were important factors which influence the EEGs background activity. PMID- 8517980 TI - [Five cases of paroxysmal sleep disturbances]. AB - Five cases with paroxysmal disturbances occurring during sleep were presented. The diagnosis of epilepsy was made in 3 cases and the diagnosis of non-epilepsy was made in 2 cases. The latter 2 cases had been treated as epilepsy. Clinical differences were not apparent on ictal manifestations between the epileptic and non-epileptic paroxysmal sleep disturbances. Seizures on awakening, which were noticed in only the epileptic cases, appeared 1 to 10 months later than sleep seizures. Final diagnosis was based on ictal EEG. Slow wave bursts were followed by alpha activity in non-epileptic cases. In epileptic cases, EEG revealed frontal dominant localized spike discharges which spread around in 2 cases and fast wave discharges in 1 cases. PMID- 8517981 TI - [Factors affecting P300 latencies in epileptic children]. AB - Auditory event-related potentials (ERPs) were recorded from 131 epileptic children of 4 to 20 years of age, and the related factors affecting P300 latencies were evaluated using multiple regression analysis. The examined factors were as follows: (1) age at P300 recording and duration of illness, (2) seizure types and epileptic syndromes, (3) anti-epileptic drugs (AEDs), (4) seizure prognosis, (5) organic brain dysfunctions, (6) x-ray CT and (7) EEG background activity and frequency of paroxysms. ERPs were elicited with the oddball paradigm. Five factors of them had significant correlations with P300 latencies. 1) P300 latencies were gradually shortened with age. 2) P300 latencies were prolonged in the patients before and during AED medication compared with those during the period of off-therapy. 3) Symptomatic partial epilepsy showed obviously prolonged P300 latencies. 4) P300 latencies were shortened with increasing alpha 2 power of EEG. 5) P300 latencies became prolonged with the length of illness. PMID- 8517982 TI - [Muscle carnitine contents in severely handicapped children with acute myoglobinuria]. AB - Muscle carnitine was measured in 3 severely handicapped children with acute myoglobinuria. Muscle total carnitine levels were 9.6 +/- 3.0 nmol/mg non collagen protein (m +/- SD, control 15.7 +/- 2.8, n = 19), and free 6.5 +/- 3.0 nmol/mg non collagen protein (m +/- SD, control 12.9 +/- 3.7, n = 19), muscle free carnitine was significantly low in them. Serum carnitine was measured in 22 severely handicapped children. Serum total carnitine was 48.9 +/- 12.3 nmol/ml (m +/- SD, control 60.3 +/- 11.7, n = 14), and free 37.7 +/- 10.0 nmol/ml (m +/- SD, control 46.0 +/- 12.5, n = 14), serum carnitine was also significantly decreased. Secondary muscle and serum carnitine depletion might be one of the potential cause of myoglobinuria in severely handicapped children. PMID- 8517983 TI - [Prevalence rate of the severely mentally and physically disabled children in Gunma Prefecture]. AB - Children were studied on distribution of the severely mentally and physically disabled aged 6 to 15 years in Gunma Prefecture as of September 1, 1991. They were all bedridden or able to sit, but could not stand or walk, even with support. Today, all the Japanese should attend elementary school as well as junior high school. Even though they are severely disabled, they are all registered by the regional Board of Education, where we could get exact data on the disabled children throughout Gunma Prefecture. We collaborated with the regional Board of Education, the Child Consultation Center of Gunma Prefecture and 6 hospitals for the disabled. A total of 129 cases were found. The population of schoolboys and schoolgirls aged 6 to 15 years of age was 236,000, most of whose guardians were residents of this prefecture, and the prevalence rate was 0.55/1000. Among 129 cases, 53 cases (41.1%) were institutionalized and 76 cases (58.9%) were cared for at home. Fifty-nine cases (45.7%) were males and 70 cases (54.3%) were females. Thirty-four cases were aged 6 to 7 years (26.4%) and older cases declined probably due to premature deaths. Ninety-four of the 129 cases (72.9%) were bedridden and mentally retarded with IQs 20 or less. PMID- 8517984 TI - [Clinical significance of measurement of pressure volume index, outflow resistance of cerebrospinal fluid and absorption pressure in infantile hydrocephalus]. AB - Measurements such as intracranial pressure-volume index (PVI), out flow resistance (Ro), and absorption pressure (Abs) of the cerebrospinal fluid were utilized for intracranial bio-mechanical analyses of four infants who suffered from hydrocephalus prior to insertion of a ventriculoperitoneal (V-P) shunt and 4 infants suffering from malfunction of a previously inserted V-P shunt. Changes in parameters immediately before and 14 days after insertion of a V-P shunt and before and after revision of a malfunctioning shunt were compared. Further, to clarify the clinical significance, in infantile hydrocephalus, of changes in bio mechanical parameters, measurement results also were compared with the outcome of V-P shunts by assessing changes in pre- and post-operative reduction in size of the frontal horn of the lateral ventricles (frontal horn index; FHI), and also by Watanabe's method of neurological evaluation. Among 7 infants whose Ro and Abs prior to shunting were abnormally high when compared with normal values reported by other investigators, values such as FHI, Ro and Abs tended to return, after the V-P shunt insertion, toward normal values in association with marked improvement of neurological status. The results appear to indicate that high Ro and Abs values recorded prior to surgery are factors predicting good functional outcome of a hydrocephalic infant after V-P shunt insertion. It should be noted, however, that in 3 out of the 7 cases, both preoperative and postoperative PVI values were found to be higher than the predicted PVI values reported by Shapiro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8517985 TI - [A girl with Down syndrome complicated by moyamoya disease and symptomatic atlanto-axial instability]. AB - We reported a girl of Down syndrome with both moyamoya disease and spinal cord compression due to atlanto-axial instability. At the age of 3 years, she presented with muscle weakness of gradual onset, and could not walk without support. On admission, at the age of 6, she presented with spastic paraparesis with predominance on the right side. To explain her neurological manifestations, we performed cranial MRI first, and found multiple infarctions with predominance on the right hemisphere, the occlusive changes of internal carotid and middle cerebral arteries, and signal void flow signs in basal ganglia, which suggested moyamoya disease. Although diagnosis of moyamoya disease was confirmed by cranial angiography, discrepancy between clinical manifestations (right-side dominant spasticity) and MRI findings (right-side dominant infarctions) could not be explained. Thereafter, we performed cervical MRI, which showed severely compressed lesions with predominance on the right side, corresponding to her clinical manifestations. It is essential to perform not only cranial but also cervical MRI for a patient with Down syndrome presenting neurological complications. PMID- 8517986 TI - [Atypical early infantile epileptic encephalopathy with suppression-burst]. AB - We report an 8-month-old infant with tonic spasms that started at the age of 38 days and occurred in clusters. He had no myoclonic seizures, or erratic myoclonus. Repeated simultaneous video-EEG monitoring revealed abrupt flexion of the neck and extremities associated with high voltage slow waves preceded by multiple spikes and/or sharps, which resembled spasms seen in West syndrome. Interictal EEGs, before and after the onset of epilepsy, showed suppression burst. The bursts consisted of irregular high voltage slow waves mixed with poorly developed spike before the onset of epilepsy. On the other hand, duration of suppression phase ranged from 1 to 27 seconds, and burst-burst interval from 2 to 30 seconds after the onset of epilepsy. He was considered as having an atypical early infantile epileptic encephalopathy with suppression burst. PMID- 8517987 TI - [MRI and autopsy findings in the brain of a child born with extreme prematurity]. AB - We present the brain autopsy and MRI findings in a four-year-old boy who was born at 23 weeks of gestational age and 700 gram of birthweight and experienced an episode of cardiac arrest at 10 months of age. Neuropathological study showed the findings compatible with cardiac arrest syndrome, the gliosis or neuronal loss of extensive cerebral lesions including the cerebral white matter and cortex, basal ganglia, cerebellum and hippocampus, and large ulegyric formation in the bilateral parietal and occipital lobes, as well as the periventricular leukomalacia, which characterize hypoxic-ischemic insult in the brain of preterm infant. MRI performed eight months before his death demonstrated prominent atrophy and periventricular and parenchymal hyperintensity of the bilateral occipital lobes consistent with the above pathological findings. PMID- 8517989 TI - [Two cases whose epileptic attacks disappeared at the time of infection]. AB - Two cases with secondary generalized epilepsy whose epileptic attacks disappeared abruptly were reported. Permanent improvement was observed in case 1 with residual state of West syndrome, aged 4 years, after viral pneumonia, both epileptic attacks and epileptic discharges on EEG disappeared more than 3 years. Transient improvement was observed in case 2 with Lennox-Gastaut syndrome, aged 6 years, after an episode with insomnia, poor appetite and confusion for three days. After this episode epileptic attacks disappeared for 9 months and epileptic discharges on EEG were also markedly decreased. However, epileptic attacks relapsed following the reduction of phenytoin after 9 months. An effect resembling ketogenic diet therapy and a change of pharmacokinetics of antiepileptic drugs may be involved in the transient improvement of case 2. However, any effects involving an immunological effect and secretions of adreno cortico-hormone following after stress may be not involved in the permanent improvement of case 1. PMID- 8517988 TI - [A case of spontaneous spinal epidural hematoma]. AB - A 14-month-old girl with spontaneous spinal epidural hematoma and complete postoperative recovery was described. MRI proved to be a sensitive tool in identifying the nature and extent of this lesion. A review of literature was made with particular emphasis on the pediatric age group. PMID- 8517990 TI - [Two cases of theophylline-associated encephalopathy in childhood: clinical and CT findings]. AB - Two asthmatic children who developed status epilepticus during theophylline treatment followed by semi-coma were reported. They suffered from severe neurological sequelae. A two-year-old male received oral maintenance theophylline therapy and a four-year-old male received intravenous theophylline therapy at the time of seizures. Theophylline blood levels measured several hours after the onset of seizures were within or below the therapeutic level; 12.7 and 8.8 micrograms/ml. They had febrile convulsions prior to the onset of episode and one of them was mildly delayed in psychomotor development. Brain CT scans showed diffuse cortical low-density in the acute period. Follow up CT scans revealed progressive cortical low-density in the subacute period and subsequently reached to the peak in the 10th day and 19th day of illness respectively. We consider that the progressive and long-lasting severe cortical edema on brain CT scan is characteristic of theophylline-associated encephalopathy. PMID- 8517991 TI - [Identical twins with atypical benign partial epilepsy]. AB - Female identical twins with atypical absence in waking state and partial seizures in sleep state were reported. During atypical absence the EEGs of both cases showed bursts in bilateral parietal and temporal regions during waking state and almost continuous diffuse spike-waves during sleep. Phenytoin was effective to discontinue the seizures in both cases. These findings were compatible to atypical benign partial epilepsy first reported by Aicardi et al. A possibility of genetic cause of this disorder may be considered. PMID- 8517992 TI - [Hypercalciuria in severely handicapped children]. PMID- 8517993 TI - [Age dependency of the serum concentration of zonisamide]. PMID- 8517994 TI - Vitamin K administration to the newborn: a public health policy and service delivery dilemma. PMID- 8517995 TI - Vitamin K and childhood cancer: a dilemma in practice. PMID- 8517996 TI - Epidemiology of late onset haemorrhagic disease: a pooled data analysis. PMID- 8517997 TI - Joint statement and interim recommendations on vitamin K prophylaxis for haemorrhagic disease in infancy. National Health and Medical Research Council. The Australian College of Paediatrics and the Royal Australian College of Obstetricians and Gynaecologists. PMID- 8517998 TI - Distal hypospadias repair with preputial reconstruction. AB - This study reports the results for 27 boys who had their foreskin reconstructed at the time of a distal hypospadias repair. Preservation of the foreskin provides a useful cosmetic alternative for distal hypospadias surgery. PMID- 8518000 TI - Cyclosporin therapy in steroid-dependent nephrotic syndrome. AB - Five children with multiple relapsing steroid-dependent nephrotic syndrome were treated with continuous cyclosporin for periods ranging from 18 to 48 months. Renal biopsy showed mild mesangial proliferation in three of the children and minimal change in two. All children previously had been treated with cyclophosphamide. Cyclosporin was started during remission at 5 mg/kg per day. If a relapse occurred the dose was increased until a trough blood level of 100-250 ng/mL (HPLC) was achieved. In the initial 12 months of treatment, the mean number of relapses decreased from 6.4 +/- 0.54 (s.d.) per annum to 1.6 +/- 1.3 per annum (P < 0.01). Cyclosporin was effective in maintaining long-term remission in four of the five patients. Side effects included hypertrichosis (5) and gum hyperplasia (1). The mean creatinine clearance decreased from 126 +/- 16 to 97 +/ 22 mL/min per 1.73 m2 (P = NS). A renal biopsy in all five patients after 12 months therapy showed no nephrotoxicity. A further biopsy in one patient after 4 years therapy showed interstitial fibrosis. Cyclosporin should be considered in children with steroid-dependent nephrotic syndrome who show signs of steroid toxicity and have only a short remission period after cyclophosphamide. Serial renal biopsies are recommended if prolonged therapy is used. PMID- 8517999 TI - Prevalence of verocytotoxigenic Escherichia coli serotype O157:H7 in children with diarrhoea attending a Sydney hospital. AB - Verotoxin producing Escherichia coli, in particular serotype O157:H7, have been implicated as an important cause of acute gastroenteritis in children. This study was undertaken to determine if E. coli O157:H7 is an important cause of acute gastroenteritis in children in metropolitan Sydney. During the period from October 1990 to September 1991, stools from patients presenting with acute diarrhoea to The Children's Hospital, Camperdown, were examined for the presence of common bacterial pathogens. In addition, stools were grown on sorbitol McConkey agar and sorbitol non-fermenting organisms were serotyped with O157 antiserum by slide agglutination. The isolates were then tested with H7 antisera and investigated for the production of verocytotoxin and other pathogenic markers including plasmid-associated EHEC adhesin and chromosomally encoded attachment effacement gene. Only two strains (isolated from two different patients, 0.1% of specimens tested) were agglutinated by O157 antiserum and both were non-motile (H ). However, both strains produced verotoxin and expressed other virulence markers, suggesting that they were responsible for the diarrhoea. Both patients experienced mild, self limited gastroenteritis. We conclude that E. coli O157:H7 is an uncommon cause of acute gastroenteritis in Sydney children presenting to a children's hospital. PMID- 8518001 TI - Splenic injury in children: a 10 year experience. AB - The aim of this report was to review retrospectively the management of splenic trauma at a major Australian tertiary referral centre (Westmead Hospital) over a 10 year period. Forty-nine patients (0-15 years of age) with documented blunt splenic trauma were identified. The causes of splenic injury were road trauma (73%) and falls (27%). There were 22 minor injuries (Injury severity score [ISS] < 16) and 27 severe injuries (ISS > or = 16). All nine deaths were related to road trauma (mean ISS = 59). The investigation most commonly used was CT scanning (47%). Peritoneal lavage was performed in six patients (12%). Management involved non-operative care in 29 patients (57%), exploratory laparotomy alone in 5 (10%), splenic salvage in 2 (4%) and splenectomy in 13 (26%). This experience supports the view that non-operative management of splenic injury in haemodynamically stable children is safe and is the preferred treatment. Experienced assessment and meticulous observation is necessary. Laparotomy is indicated if there is continuing haemodynamic instability despite resuscitation. Operative management is aimed at splenic salvage with splenectomy being reserved for uncontrolled haemorrhage. PMID- 8518002 TI - Serum immunoglobulin G directed against porcine trypsin in the serum of cystic fibrosis children receiving porcine pancreatic enzyme supplements. AB - Cystic fibrosis (CF) patients require pancreatic enzyme replacement therapy to correct pancreatic insufficiency. These enzymes are derived from porcine pancreas and are known to be antigenic. To determine the possible clinical consequences, a specific ELISA was developed to detect IgG antibody directed against porcine trypsin (PTAb) in the sera of CF patients. The assay was used to evaluate the occurrence of PTAb in a cross sectional study of 103 CF patients in relation to the introduction of porcine enzyme therapy, clinical status and genotype. Antibodies against porcine trypsin were detected in the sera of 63% of patients unrelated to the age of commencement or the duration of enzyme therapy. No differences were observed in the clinical status of CF patients who had developed PTAb (n = 65) and those who had no detectable PTAb (n = 38) as determined from: the current prescribed dose of porcine pancreatic enzyme capsules; Z scores for height and weight; and respiratory function tests. It is suggested that the PTAb commonly found in the sera of CF patients are of doubtful clinical significance but the prospect of PTAb contributing to immune complex disease should be examined further. PMID- 8518003 TI - Long-term complications following bone marrow transplantation in children. AB - Seventeen children who underwent bone marrow transplantation (BMT) between 1975 and 1985 and survived for more than 2 years were evaluated for growth and development. The patients had a follow up of 2.1-13.1 years. Prior to transplant, children with malignancy had received multi-agent chemotherapy and nine had also received central nervous system irradiation. Transplant preparation for malignancy (group 1; n = 13) included high-dose cyclophosphamide (CPA) 120-200 mg/kg and total body irradiation (TBI) 10-13.2 Gy, whereas conditioning for non malignant disorders (group 2; n = 4) included high-dose CPA 200 mg/kg with or without busulphan. Patients in group 1 showed a steady decline in height velocity following initial chemotherapy and cranial irradiation and the decline was even greater following BMT. Growth hormone (GH) deficiency developed in eight of nine children tested, hypergonadotrophic hypogonadism developed in 11 who reached puberty, thyroid hormone abnormalities were encountered in four out of 10 tested and 11 of 13 developed cataracts. Patients in group 2 did not show decline in linear growth rate, thyroid hormone abnormalities or cataracts after BMT. The only child tested had normal GH levels and the two patients who reached puberty showed delayed but complete gonadal recovery. Our data demonstrate that TBI leads to significant late effects on growth and gonadal function. Contrary to previous reports, a high incidence of cataract formation is observed after fractionated TBI. Conditioning regimens TBI should be considered in children undergoing BMT. PMID- 8518004 TI - Sensory evoked potentials in inhalant (volatile solvent) abuse. AB - A study was made to determine whether children with a significant history of inhalant abuse but who lack clinical evidence of neurological abnormality have abnormal visual, auditory or somatosensory evoked potentials. Visual, auditory and somatosensory evoked potential studies were obtained from 15 such children aged 9-17 years. Eight of the children had abnormal visual or auditory evoked potentials. Somatosensory evoked potentials were normal in all. It was concluded that evoked potentials may serve as an objective marker of early neurological damage in children who abuse inhalants and demonstrate potential usefulness for counselling and intervention. PMID- 8518005 TI - Reported food consumption and dietary habits of New Zealand adolescents. AB - Six hundred and sixty-seven fifteen year old members of the Dunedin Multidisciplinary Health and Development study cohort completed a self administered food frequency and dietary habits inventory. The results show that only 14 foods were consumed on a regular basis by more than 80% of the cohort. Statistically significant differences were found between the numbers of boys and girls consuming a variety of foods; generally, more girls consumed fruits and green vegetables and more boys consumed foods rich in fat and sugar. Several differences were observed in the food consumption of three income groups: fewer adolescents in low income families consumed expensive foods such as steak. The implications of these food consumption findings and their associated gender and income differences for nutrition promotion and food policy are discussed. PMID- 8518006 TI - Birth order and risk of sudden infant death syndrome: is the true relationship negative? AB - The risk of SIDS has been reported consistently as being positively related to parity or birth order. However, the reports in question have failed to take into account the possible confounding effects of sibship size. In the present study it was reasoned that if this were done the relationship would be negative, not positive. In an analysis of births stratified by sibship size positive. In an analysis of births stratified by sibship size occurring in the years 1975-84 in the state of Oregon, it was found that the risk of SIDS in the age range 7-364 days did indeed tend to decrease with increasing birth order when sibship size was held constant. An expected tendency for SIDS rates to increase with increasing sibship size when birth order was held constant was also confirmed. This tendency is probably explained by a negative correlation between family size and socio-economic status. Non-SIDS rates behaved in a similar manner to SIDS rates. The tendency for the risk of SIDS to decrease with increasing birth order was more evident when births following a pregnancy interval of less than 12 months were excluded. PMID- 8518007 TI - Child day care and home injuries involving playground equipment. AB - The increasing number of children attending child day care has led to a corresponding concern for their safety in the absence of parental care. Previous studies have documented that the majority of injuries occurring in child day care involve falls, and that the most common consumer product associated with such falls is playground equipment. This study describes New Zealand children less than 5 years of age admitted to hospital between 1979 and 1988 for injuries associated with playground equipment located at home or a child care facility. There were 528 hospitalized home injuries involving playground equipment, and 145 such day care injuries. Fractures were the most common injury, and the head was the most commonly involved body region. Lower limb injuries were the most severe. Among the differences between home and day care injuries were the type of equipment involved. Swings were disproportionately associated with head injuries. PMID- 8518008 TI - The use of child safety restraints with nursery furniture. AB - In Australia, nursery furniture is associated with just over 6% of all injuries to children between birth and 3 years of age and 19% (or almost one in five) of all injuries in the first year of life. In the case of injury associated with prams or strollers and high chairs, the vast majority of injuries occur as the result of falls (75 and 83% respectively). Interviews with parents whose children suffered an injury as a result of a fall from a pram or stroller or from a high chair indicate that only a small proportion of the children (28 and 25% respectively) were wearing any form of safety restraint prior to their injury despite the fact that, in both samples, the percentage of safety restraints fitted was about 80%. The potential for serious injury from such falls is great as most injuries in both groups (96 and 75% respectively) were to the head. One death associated with a stroller and one death as a result of a fall from a high chair have been recorded for Victoria between 1985 and 1988. In the absence of mandatory requirements for the design and manufacture of nursery furniture, there is a need to provide information about nursery furniture safety to parents and care-givers through nursery furniture retailers and through maternity hospitals and child health centres. In particular, the promotion of the correct use of an appropriate and effective child restraint is a relatively simple and inexpensive measure that could prevent up to 80% of all injuries associated with the three items of nursery furniture most often related to injury: strollers or prams, high chairs and change tables. PMID- 8518009 TI - Non-traffic child pedestrian injuries. AB - All non-traffic child pedestrian deaths and injuries resulting in hospitalization in the Auckland region over a 5 year period were identified from coroner's and hospital records. There were eight deaths (0.77/100,000 children per year) and 91 hospital admissions (8.7/100,000 children per year). Close to half (48%) of the non-traffic pedestrian injury admissions had been misclassified as traffic pedestrian injuries. Eighty-seven per cent of the non-traffic pedestrian injury deaths and 93% of the injuries occurred in residential driveways, most often involving a child run over by a reversing vehicle. Further studies are required to determine the most effective strategies for the prevention of non-traffic child pedestrian injuries. PMID- 8518010 TI - The incidence of labial fusion in children. AB - A retrospective study of 9070 female infants born at the Foothills Provincial Hospital was conducted to determine the incidence of labial fusion at birth. A prospective study was also conducted on 1970 female patients assessed through a paediatric outpatient clinic to determine the incidence of labial fusion in this population. None of the newborn infants had labial fusion. Thirty-five children (1.8%) assessed at the paediatric outpatient clinic were found to have labial fusion with a peak incidence at 13-23 months of age (3.3%). PMID- 8518011 TI - Retrospective diagnosis of medium chain acyl-CoA dehydrogenase deficiency. AB - A male infant is reported who died suddenly and who at post-mortem had pathological evidence suggestive of a genetic defect of fatty acid beta oxidation. A specific diagnosis could not be made enzymatically because of unavailability of suitable tissue for assay. The diagnosis of medium chain acyl CoA dehydrogenase (MCAD) deficiency was made by specific mutation analysis using the polymerase chain reaction and DNA extracted from the newborn screening card of this infant. This powerful new molecular diagnostic technique should prove to be of use in similar circumstances. PMID- 8518012 TI - Oesophageal perforation caused by a coin. AB - An unusual consequence of an initially asymptomatic coin ingestion is described to alert paediatricians that coins are not always innocuous. The case illustrates the need to investigate subtle but persistent symptoms, and also describes the surgical approach to coins that erode through the oesophageal wall. PMID- 8518013 TI - Inadequate management of breast feeding. PMID- 8518014 TI - Possible skin allergy reaction to oral vitamin K. PMID- 8518015 TI - What is the correct hormonal treatment for prostate cancer? PMID- 8518016 TI - Treatment results, survival and prognostic factors in 109 inflammatory breast cancers: univariate and multivariate analysis. AB - Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5 fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure. PMID- 8518017 TI - Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. The Italian Prostatic Cancer Project (PONCAP) Study Group. AB - From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone. PMID- 8518018 TI - Central small size breast cancer: how to overcome the problem of nipple and areola involvement. AB - For centrally located small tumours we have sought, with the aid of a plastic surgeon, to achieve the same radicality as in the other quadrants, while achieving a good cosmetic result. We considered 37 patients with small centrally located breast carcinoma, in whom we performed a new surgical technique. From analysis of this series it emerged that a high percentage (54.1%) had nipple and areolar involvement, suggesting their removal; it is no problem to sacrifice these when a good cosmetic result can be achieved by plastic remodelling. PMID- 8518019 TI - The value of twice yearly bronchoscopy in the work-up and follow-up of patients with laryngeal cancer. AB - The aim of this retrospective study was to investigate the usefulness and feasibility of twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer. In 170 selected patients, 500 (both initial and during follow up) bronchoscopies were performed. There was a maximum follow-up of 34 months. 5 (2.8%) male patients developed lung cancer. In only 2 of them was the diagnosis based on bronchoscopy alone. After treatment with curative intent, both patients developed a recurrent lung carcinoma. According to most patients' experience, regular bronchoscopy is unpleasant. It is concluded that twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer is not useful as a routine procedure. At present, chemoprevention of second primary tumours seems the most promising adjunctive treatment modality. PMID- 8518020 TI - Prednimustine (Sterecyt) versus cyclophosphamide both in combination with methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. AB - 153 women with advanced breast cancer were randomly allocated for treatment with SMF [prednimustine (Sterecyt) + methotrexate + 5-fluorouracil, 83 patients] or CMF (cyclophosphamide+methotrexate+5-fluorouracil, 70 patients). Prednimustine was administered orally 100 mg/m2 daily, for 5 days, and cyclophosphamide was administered orally 100 mg/m2, for 14 days, each, every 4 weeks. Methotrexate was given at a dose of 40 mg/m2 and 5-fluorouracil at 600 mg/m2 on day 1 and 8, every 4 weeks. Leucovorin was used in 39 patients to alleviate mucositis. The two treatment groups were balanced in terms of age, performance status, lymph node status, histology, menopausal status and previous therapy. Response was evaluated in 140 patients. Of 76 patients treated with SMF, 4 had a complete and 21 a partial response (CR+PR = 33%), 40 had no change (NC) and 11 had progressive disease (PD). Of 64 patients treated with CMF, 3 had a complete and 18 a partial response (CR+PR = 33%), 30 had no change (NC) and 13 had progressive disease (PD). Time to treatment failure and survival were similar in both groups. A relationship between haematological and gastrointestinal toxicity and therapeutic efficacy was demonstrated with a superior survival and response rate recorded for patients with such toxicity than in patients without. Haematological toxicity was, in general, mild to moderate with no difference between the two groups. Alopecia (P = 0.008), nausea/vomiting (P = 0.02) and euphoria (P = 0.03) were more common in the CMF-treated group. Diarrhoea was more common in the SMF group (P = 0.03). In conclusion, SMF seems to be as efficient as CMF with regard to response rate, time to treatment failure and survival. However, SMF was tolerated better than CMF. PMID- 8518021 TI - Potential contribution of 131I-labelled monoclonal anti-CEA antibodies in the treatment of liver metastases from colorectal carcinomas: pretherapeutic study with dose recovery in resected tissues. AB - 20 patients with liver metastases from colorectal carcinoma undergoing laparotomy received 15-60 mg intravenously, either intact or fragments of, anti carcinoembryonic antigen (anti-CEA) monoclonal antibodies labelled with 0.55-1.48 GBq (15-40 mCi) of 131I, 3-8 days prior to operation. The uptake measured per gram of metastases ranged from 0.33 to 6.6 x 10(-3%) of injected dose. Tumour to liver uptake ratios ranged from 2 to 33. The radiation dose, estimated in 6 patients (3 of each group), for an extrapolated dose of 3.7 GBq (100 mCi) of 131I ranged from 0.3 to 0.8 Gy in normal liver or spleen (an acceptable estimate for bone marrow radiation dose) and from 3.4 to 8.2 Gy to the hepatic metastases, indicating that probably other therapeutic modalities should be associated with radioimmunotherapy. PMID- 8518022 TI - Clinical heterogeneity of hereditary breast cancer and its impact on screening protocols: the Dutch experience on 24 families under surveillance. AB - We investigated 24 families who satisfied a set of criteria for hereditary breast cancer. Five families had only breast cancer, four a combination of breast and ovarian cancer and the remaining 15 had also a variety of other cancers. The families include 86 patients, 78 of which had a malignant tumour and the rest had a benign lesion in the breast. The median age at diagnosis of the breast cancer was 47 years. Three of the 24 families were of a late onset variant. 58 of the 86 patients were symptomatic while 18 were identified during presymptomatic screening because of a positive family history. In 10 cases the reason for referral was not known. 56 of the symptomatic patients had a malignant breast lesion, 52% of which were with lymph node metastasis whereas 12 of the screening group had breast cancer with 2 patients showing lymph node involvement (P = 0.06). 22 of the symptomatic patients and none of the screening patients died of breast cancer after a median observation period of 6 and 7 years, respectively (P < 0.05). PMID- 8518023 TI - Low-dose dopamine induces early recovery of recombinant interleukin-2--impaired renal function. AB - Recombinant interleukin-2 (rIL-2) can produce impairment of renal function with hypotension, fluid retention, elevated blood urea nitrogen, oliguria and low fractional sodium excretion; these side-effects are a common cause of reduction or interruption of rIL-2 infusion. The aim of this study was to investigate the control and treatment of renal toxicity induced by rIL-2 therapy. Here we show that dopamine, at a low dose of 2 micrograms/kg/min, completely prevented renal toxicity induced by rIL-2. While continuing rIL-2 therapy, 24-h continuous infusion of low-dose dopamine produced a rapid normalisation of urine output and a significant decrease in serum creatinine levels and body weight (P < 0.01), with an early and complete recovery of the rIL-2--impaired renal function: mean recovery time of renal function in patients treated with dopamine was significantly lower (P < 0.05) than in nontreated patients (4.8 days vs. 10 days, respectively). PMID- 8518025 TI - The influence of chemotherapy on survival after recurrence in breast cancer--a population-based study of patients treated in the 1950s, 1960s and 1970s. AB - In a population-based study survival after recurrence was compared in three cohorts of patients with a primary diagnosis of breast cancer in 1959, 1969 and 1979, respectively. The use of chemotherapy after recurrence in these cohorts was either none, sporadic or widespread. This allowed a retrospective analysis of the survival impact of chemotherapy. Given the basic assumption that the natural history of breast cancer and the influence of endocrine therapy have not changed significantly during the 20-year period covered by the study, our data suggest that chemotherapy in recurrent breast cancer prolongs survival by 9.5 months in patients who survive more than 2 weeks from the start of treatment for this recurrence. PMID- 8518024 TI - Treatment of FIGO (1971) stage I endometrial carcinoma with intensive surgery, radiotherapy and hormonotherapy according to pathological prognostic groups. Long term results of a randomised multicentre study. AB - A multicentre trial on patients with apparent stage I endometrial carcinoma was conducted with the aims of defining a treatment plan on the basis of the pathological disease extension and of evaluating the effectiveness of adjuvant medroxyprogesterone acetate (MPA). After surgery, patients with disease limited to the endometrium did not receive any further treatment. Patients with inner myometrial invasion and well or moderate differentiation were randomised to no further treatment vs. MPA 100 mg orally twice a day for 12 months; patients with moderate or deep myometrial invasion or undifferentiated grade were randomised to radiotherapy on pelvis vs. radiotherapy plus MPA, and patients with node-positive disease (N+) were submitted to radiotherapy on pelvis and para-aortic nodes vs. radiotherapy plus MPA. At 84 months, analysis as intention to treat on 856 patients shows a high relapse-free survival, whereas it did not show any significant difference between the MPA-treated and untreated groups. The study indicates that relapse-free survival is influenced by a treatment based on the pathological extension of the disease and that adjuvant hormonotherapy does not improve the cure rate. PMID- 8518026 TI - Selective reversal of vinblastine resistance in multidrug-resistant cell lines by tamoxifen, toremifene and their metabolites. AB - In this study we describe the effects of tamoxifen, toremifene and their 4 hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected. PMID- 8518027 TI - Potentiation of tumour necrosis factor-mediated cell killing by VP16 on human ovarian cancer cell lines. In vitro results and clinical implications. AB - Synergism between recombinant human tumour necrosis factor (rHuTNF) and DNA topoisomerase II inhibitor VP16 during the killing of cells has been studied in six human ovarian cancer cell lines (A2774, A2780, SW626, IGROV-1, SKOV3, Pa1) and a cervical carcinoma cell line (Me180). Studies were performed using an assay of colony formation inhibition (drug treatment for 1 h) and a growth inhibition assay (continuous exposure for 20 h). Concomitant treatment of cells with VP16+rHuTNF enhanced cell killing in all the cell lines tested--an effect observed in both short- and long-term cytotoxicity assays. This study suggests that the activity of VP16 in ovarian cancer cell lines might be enhanced by rHuTNF in in vitro models. PMID- 8518029 TI - Correlation of morphological FAB classification and immunophenotyping: value in recognition of morphological, cytochemical and immunological characteristics of mixed leukaemias. AB - Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML. PMID- 8518028 TI - The serial study of c-myc expression in bone marrow biopsy specimens during treatment for acute myelogenous leukaemia. AB - The AMEX method of fixation permitted the serial study of c-myc expression in bone-marrow (BM) biopsies obtained from 6 patients with acute myelogenous leukaemia (AML) and one with myelodysplastic syndrome (MDS) during therapy with various cytotoxic and bioactive agents. BM cytotoxic therapy and therapy with bioactive agents was capable of altering c-myc expression in vivo. While cytotoxic therapy was generally associated with a fall in myc expression, it did not produce a dramatic effect on myc expression. Recombinant human granulocyte macrophage colony-stimulating factor (RhGM-CSF) can increase and retinoic acid/alpha-interferon can decrease c-myc expression in myeloid cells in vivo. PMID- 8518030 TI - Tumour necrosis factor increases tumour uptake of co-administered antibody carboxypeptidase G2 conjugate. AB - Increased tumour uptake of antibodies and antibody-drug conjugates has been demonstrated following pretreatment of animals with recombinant human tumour necrosis factor-alpha (rTNF-alpha) and interleukin 2 immunoconjugates. The experiments reported here were performed to determine whether improved tumour localisation of antibody-carboxypeptidase G2 conjugates could be achieved, with a view to applying this technology to antibody-directed enzyme-prodrug therapy (ADEPT). B6CF1 mice bearing the Ly-2.1+ murine thymoma E3 were simultaneously injected with 2.0 micrograms rTNF-alpha and 3.5 micrograms (74kBq) 125I-labelled murine anti-Ly-2.1-CPG2 conjugate. Mice in control groups received phosphate buffered saline in place of rTNF-alpha. The conjugate corresponded in molecular weight to a mixture of 1:1 and 2:1 (CPG2:IgG) conjugate and retained its antigen binding specificity and enzymic activity in vitro. A significant increase in tumour uptake was observed 24 h after administration when rTNF-alpha-treated animals were compared to controls (28.1 +/- 9.7%/g and 11.6 +/- 2.3%/g, respectively). Other tissues, most notably gut, skin and kidney also showed an increased localisation of conjugate. By 48 h, analysis of tissue:blood ratios demonstrated that although tumour:blood ratios were significantly higher in rTNF alpha-treated animals (P < 0.05), all the other tissue:blood ratios were not significantly different between the two groups. PMID- 8518031 TI - Plasminogen activators and plasminogen activator inhibitors in human colorectal carcinoma tissues are not expressed by the tumour cells. AB - Plasminogen activators (PA) have been implicated with the degradation of extracellular matrix during the invasive growth of metastasising tumour cells. The significance of PA expression in tumour cells for the in vivo growth of malignant tumours is still a matter of debate. We, therefore, performed immunohistological studies on human colon tumours using monoclonal antibodies against urokinase- (u-PA) and tissue-type plasminogen activator (t-PA) as well as against plasminogen activator inhibitors 1 and 2 (PAI-1, PAI-2). Normal colorectal mucosa of seven samples was negative for all four constituents of the PA system. Tumour epithelium of 64 colorectal carcinomas and 10 liver metastases was consistently negative for both, PA and their inhibitors. However, two of four human colon carcinoma cell lines weakly expressed u-PA, PAI-1 and PAI-2. Intestinal dendritic or fibroblast-like cells within the tumour tissue strongly expressed u-PA and, at a lower level, also t-PA, PAI-1 and PAI-2. Vascular endothelial cells were weakly positive for all components of the PA system in colon carcinoma. Our findings indicate that colon carcinoma cells in their natural environment do not express constituents of the PA system. PA activity, previously found in colon carcinoma tissue, is most likely derived from interstitial cells. PMID- 8518032 TI - Thyroid cancer in suppressed contralateral lobe of patients with hot thyroid nodule. AB - We studied 60 patients with thyrotoxicosis due to single toxic nodule. At surgery in 3 patients (5%) a papillary carcinoma has been detected in the contralateral suppressed lobe. Thyroid function tests and thyroid scan confirmed thyrotoxicosis. Thyroid stimulating hormone (TSH) was undetectable in all patients. It is common opinion that differentiated thyroid tumour growth is TSH dependent. On the basis of our study two hypotheses are possible: (1) the development of thyroid carcinoma precedes the adenoma and suppressed TSH levels inhibit tumour growth; (2) suppressed TSH levels do not protect patients from the occurrence of cancer. In the evaluation of hot thyroid nodule we suggest careful ultrasonographic control in order to look for nodules outside the adenoma. A complete surgical examination of the whole thyroid gland is required and intraoperative biopsies are advocated in abnormal areas. PMID- 8518033 TI - The use of the polymerase chain reaction to detect minimal residual disease in childhood acute lymphoblastic leukaemia. PMID- 8518034 TI - Black (air-cured) and blond (flue-cured) tobacco cancer risk. IV: Molecular dosimetry studies implicate aromatic amines as bladder carcinogens. AB - Tobacco smoking causes a major fraction of male urinary bladder cancers and the relative risk of bladder cancer is reported to be two to three times higher for smoking of black (air-cured) than for smoking of blond (flue-cured) tobacco. In molecular dosimetry studies to examine the hypothesis that aromatic amines in tobacco smoke are primarily responsible for bladder cancer, the higher bladder cancer risk in smokers of black tobacco was correlated with two to five times higher exposure to carcinogenic aromatic amines present in black tobacco smoke, notably 4-aminobiphenyl (ABP). For the same amount of smoking, black tobacco smokers had levels of ABP-haemoglobin (Hb) adducts 1.5 times higher and excreted a 1.8-fold higher level of urinary mutagens. These mutagens were characterised as aromatic amines, and included the heterocyclic amine 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP), a known mutagen and multiorgan/species carcinogen. In smoking volunteers, the ABP-Hb adduct level depended significantly on the acetylator and P-450IA2 phenotypes, being 1.3- to 1.5-fold lower in fast acetylators, slow/intermediate P-450IA2 individuals. The N-(deoxyguanosine-8-yl) ABP adduct was a major smoking-related DNA adduct in bladder biopsies from surgical patients. It was also tentatively identified in exfoliated urothelial cells of smoking volunteers, who showed a significant and linear correlation between adduct levels of ABP with Hb and with deoxyguanosine in urothelial DNA; both were related to number of cigarettes smoked per day. Levels of several smoking-related DNA adducts in urothelial cells were 2-20 times elevated in smokers. Similar convex dose-response relationships have been found between the number of cigarettes smoked and the relative risk for bladder cancer and between the levels of ABP-Hb adducts and markers of recent smoking. A possible explanation is that fast and slow acetylators have different susceptibility to aromatic amine carcinogens. Case-control studies have consistently revealed an excess of variable magnitude of slow acetylators in subgroups exposed occupationally to carcinogenic aromatic amines. Altogether, results from these studies reinforce the association between cigarette smoking, carcinogen-DNA adducts in urothelial cells, and implicate primary aromatic and possibly heterocyclic amines as bladder carcinogens. PMID- 8518035 TI - Laboratory prediction of clinical chemotherapeutic drug resistance: a working model exemplified by acute leukaemia. AB - Recent research into mechanisms of resistance to chemotherapy in acute leukaemia has been focused on various protective mechanisms at the cellular level, such as drug uptake, efflux, metabolism and DNA repair mechanisms, while therapeutic failures due to other potentially important causes have received relatively little attention. Here we describe a simple model to account for three major determinants of tumour response in acute leukaemia: cellular drug sensitivity, leukaemic cell regrowth potential and systemic drug exposure. Possible ways of measuring these parameters are discussed. It is suggested that laboratory estimation of these parameters may provide valuable information on clinical drug resistance and may help to design more adequate treatment strategies for the individual patient. PMID- 8518036 TI - Epirubicin, etoposide and cisplatin in advanced pancreatic carcinoma. PMID- 8518037 TI - Phase II trial of iproplatin in advanced squamous cell carcinoma of the head and neck, oesophagus and lung. PMID- 8518039 TI - Low frequency of NF1 gene mutations in malignant gliomas. PMID- 8518038 TI - High-dose folinic acid, 5-fluorouracil bolus and infusion in advanced pancreatic adenocarcinoma: a pilot study. PMID- 8518040 TI - Neurotoxicity following weekly therapy with folinic acid and high-dose 5 fluorouracil 24-h infusion in patients with gastrointestinal malignancies. PMID- 8518041 TI - EAP in advanced gastric cancer. PMID- 8518042 TI - Haemorrhagic cystitis requiring cystectomy after cyclophosphamide and radiotherapy. PMID- 8518044 TI - The science base of dental education. PMID- 8518043 TI - Local response and long-term results of preoperative M-VAC regimen in regionally advanced transitional cell carcinoma of the bladder. PMID- 8518045 TI - Sugars and the dental health of children. PMID- 8518046 TI - Duplication of maxillary molars. PMID- 8518047 TI - 'Safety in radiation'. PMID- 8518048 TI - The effect of amoxycillin versus penicillin V in the treatment of acutely abscessed primary teeth. AB - A clinical study was carried out to compare the efficacy of a short course, high dose amoxycillin versus a conventional penicillin regimen in the treatment of acute abscessed primary teeth. In a blind way children were assigned to either group A (amoxycillin) or group B (penicillin). The efficacy of the antibiotics was assessed using the clinical parameters of pain, swelling, tenderness, mobility and lymphadenitis. The results showed a general trend of less swelling in patients in group A as compared with patients in group B. This was significant at days 1 and 7 for the operators assessment (Mann Whitney U test; z = 2.48 and z = 2.12). More teeth in group A were considered suitable for first stage pulpectomy by day 7 (c2 test; P 0.037 pounds). A short course, high dose amoxycillin regimen proved as efficacious as a conventional penicillin regimen. PMID- 8518049 TI - A comparison of two in vitro methods for assessing the fitting accuracy of composite inlays. AB - Composite inlays were fabricated in standardised cavities cut into aluminum and perspex blocks using a computer controlled milling process. Four materials were used to construct the inlays. These were fabricated using an indirect technique following the manufacturers' recommendations, where applicable. In addition, for one of the composites, the fabrication procedures were modified. The fitting accuracy of the restorations was assessed by taking elastomeric impression wash replicas of the luting space and by examination of sectioned restored units using image analysis. The former method indicated significantly reduced fitting accuracy when either use of die spacer or secondary curing was omitted from restoration construction resulting in incomplete seating. The sectioning technique indicated that more factors appeared to significantly reduce fitting accuracy including bulk packing, alteration in curing time, omission to die spacer and the final polishing procedure. This method also provided more specific information concerning sites of premature contact. One material gave rise to significantly greater film thicknesses using both methods of assessment. No direct correlation was found between the two techniques of fit evaluation but both methods taken together provided complementary information. PMID- 8518050 TI - Bronchogenic carcinoma presenting as a periapical infection. AB - This case report describes a metastatic bronchogenic deposit involving the lower lip and the adjacent bone in the lower incisor region. The presenting symptoms were very similar to those of a dentoalveolar infection and extraction of the lower incisor teeth failed to provide any relief. Comparison of radiographs taken 6 months earlier suggested that the metastatic deposit very probably spread from the lower labial sulcus into a site of periapical infection, involving the lower incisors and the adjacent bone. PMID- 8518051 TI - Aspiration or just plain suckers. AB - Aspiration is one of the most essential services in the dental surgery, for patient comfort, clear vision and assistance with asepsis control, and is imperative during GA/RA procedures for the safety of the patient and for the removal of anaesthetic gases from the working environment. It should be noted that not all vacuum motors are suitable for this application as some brush by pass motors could present sparking problems if used with these gases. PMID- 8518052 TI - Smile with a service. PMID- 8518053 TI - Quality of life assessment in patients with heart disease. PMID- 8518054 TI - Angiotensin converting enzyme inhibitors in heart failure: how good are they? PMID- 8518055 TI - Is there such a thing as a normal sinus rate? PMID- 8518056 TI - Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. AB - OBJECTIVE: To assess the size of the lipid pool and the number of smooth muscle cells and monocyte/macrophages in human aortic plaques that were intact and to compare the results with those in aortic plaques undergoing ulceration and thrombosis. DESIGN: The lipid pool was measured as a percentage of the total cross sectional area of the plaque. Immunohistochemistry was used to identify cell types (monocytes/macrophages (M phi) by EBM11 and HAM56, smooth muscle cells by alpha actin). The area of the tissue occupied by each cell type was measured by quantitative microscopy in the peripheral (shoulder) area of the plaque and the plaque cap. Absolute counts of each cell type were expressed as the ratio of SMC:M phi. MATERIAL: Aortas were obtained at necropsy from men aged less than 69 years who died suddenly (within 6 hours of the onset of symptoms) of ischaemic heart disease. 155 plaques from 13 aortas were studied. Four aortas showed intact plaques only (group A, n = 31). Nine aortas showed both intact plaques (group B, n = 79) and plaques that were undergoing thrombosis (group C, n = 45). RESULTS: In 41 (91.1%) of the 45 plaques undergoing thrombosis (group C) lipid pools occupied more than 40% of the cross sectional area of the plaque. Only 12 (10.9%) of the 110 intact plaques (groups A + B) had lipid pools of this size. The mean size of the lipid pool in plaques of groups A, B, and C was 12.7%, 27.3% and 56.7% respectively. Compared with intact plaques those undergoing thrombosis contained a smaller volume of smooth muscle cells (2.8% v 11.8%) and a larger volume of monocyte/macrophages (13.7% v 2.9%) in the plaque cap. The ratio of the number of smooth muscle cells to monocytes/macrophages was 7.8 in group A plaques, 4.1 in group B plaques, and 1.0 in group C plaques. This gradient was the result of an absolute increase in monocyte/macrophages and an absolute decrease in smooth muscle cells. CONCLUSIONS: In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap. PMID- 8518057 TI - Aspects of psychological and social morbidity in patients awaiting coronary artery bypass grafting. AB - OBJECTIVES: To assess anxiety, depression, and social adjustment in patients awaiting coronary artery bypass surgery. DESIGN: Patient completed questionnaire study. SETTING: Regional cardiothoracic centre. PATIENTS: 109 questionnaires were sent to patients on the waiting list of two cardiothoracic surgeons. Sixty eight (62%) were returned and 15 (22%) of the respondents were women. There was no difference in the response rates for men (53/84) 63% and women (15/25) 60%. MAIN OUTCOME MEASURES: Anxiety and depression were assessed by the hospital anxiety and depression (HAD) scale. Social functioning was assessed by several nine point rating scales on which patients indicated how their work, family relationships, social activities, private leisure activities, and home management were impaired. Patients also indicated the severity of their cardiac symptoms on a questionnaire based on the New York Heart Association classification for the assessment of the functional state of patients with heart disease. RESULTS: On the HAD scale 19 (28%) patients scored in the clinically significant range for anxiety. Time spent on the waiting list was positively and significantly related to anxiety (p = 0.05). Thirty two (47%) patients scored in the clinically significant range for depression. Time spent on the waiting list was positively and significantly related to depression (p = 0.005). Positive and significant relations were found between time spent on the waiting list and impairment of work (p = < 0.0001), family relationships (p = < 0.0001), private leisure activities (p = < 0.0001), and social activities (p = 0.004). No correlation was found between any of the above variables and the indicated level of clinical symptoms. CONCLUSIONS: This study documents previously unreported associations between the time patients wait for coronary artery surgery and levels of anxiety, depression, and social functioning. Conclusions regarding the causes of these symptoms cannot be made from this small population of patients but these results do suggest that these associations should be studied further. PMID- 8518058 TI - Circadian and seasonal factors in the pathogenesis of acute myocardial infarction: the influence of environmental temperature. AB - OBJECTIVE: To determine the circadian and seasonal variations in the incidence of acute myocardial infarction and the influence of environmental temperature. PATIENTS: 633 consecutive patients with acute myocardial infarction admitted to a coronary care unit over four years. SETTING: Coronary care unit in a district general hospital. DESIGN: An observational study. RESULTS: The onset of acute myocardial infarction had a circadian rhythm with a peak in the second quarter of the day. A seasonal variation was also found with a significant winter peak. There was, however, an excess of infarctions on colder days in both winter and summer indicating that the effect of environmental temperature on the onset of acute myocardial infarction is independent of the time of year. CONCLUSION: Acute myocardial infarction is more common in winter and more common on colder days, independent of season. Environmental temperature may play an important part in the pathogenesis of acute myocardial infarction. PMID- 8518059 TI - Core and peripheral temperature response to exercise in patients with impaired left ventricular function. AB - OBJECTIVE: Exercise induced hypotension is a specific but insensitive indicator of severe coronary artery disease. Skin blood flow is subject to control by baroreceptor mediated reflexes as well as thermoregulatory reflexes. Monitoring skin temperature or the skin to central temperature gradient may be a more sensitive indicator of impaired cardiac output response to exercise than hypotension. DESIGN AND PARTICIPANTS: Central and skin temperature changes associated with exercise were studied in 10 normal volunteers and eight patients with impaired resting ventricular function due to ischaemic heart disease. Patients exercised according to a modified Bruce protocol. The two sample independent t test was applied to compare the central and peripheral temperatures in the two groups at three minute intervals during exercise and at two minute intervals after exercise. RESULTS: A significant decrease was found in mean (1 SEM) central temperature on exercise in our patient group (98.2(0.2) degrees F to 97.2(0.3) degrees F), compared with the normal increase in central temperature (97.7(0.2) degrees F to 98.3(0.3) degrees F). Mean (1 SEM) skin temperature changes reflected the expected skin blood flow changes with exercise in normal subjects. In the patient group skin temperature declined during exercise (89.7(2.1) degrees F to 86.6(1.7) degrees F) and was significantly lower than normal from six minutes onwards. CONCLUSIONS: The abnormal peripheral temperature changes of patients with impaired resting ventricular function is an early and sensitive indicator of an abnormal haemodynamic response to exercise. It is possible that skin temperature measurement during exercise could help detect exercise induced ventricular dysfunction due to ischaemia or impaired cardiac output due to valvar heart disease. PMID- 8518060 TI - Anticardiolipin antibodies in ischaemic heart disease: marker or myth? AB - OBJECTIVES: To assess the incidence and significance of anticardiolipin antibodies after myocardial infarction and in unstable angina. DESIGN: A prospective study of all patients under 60 admitted to the coronary care unit over a 12 month period with a diagnosis of acute myocardial infarction who were followed up for a further 12 months. Patients admitted with unstable angina were similarly assessed but not followed up. Anticardiolipin antibody concentrations were compared with those of age matched controls. SETTING: A district general hospital. PATIENTS: 307 patients with acute myocardial infarction and 160 patients with unstable angina. RESULTS: Anticardiolipin antibody concentrations in the two patient groups did not differ significantly from those in the control groups. Antibody concentrations were not related to a history of angina or myocardial infarction nor were they related to subsequent cardiovascular complications. CONCLUSION: This study shows no significant association between anticardiolipin antibody concentrations and either myocardial infarction or unstable angina. PMID- 8518061 TI - Troponin T release after heart transplantation. AB - BACKGROUND: For the diagnosis of myocardial cell damage the measurement of the serum concentrations of myofibrillar antigens has several potential advantages over the assessment of traditional serological markers. These include the expression of myofibrillar antigens as cardiospecific isoforms and their high intracellular concentrations. Recently a sensitive and specific enzyme immunoassay for cardiac troponin T has been developed that shows little cross reactivity with skeletal isoforms. OBJECTIVE: To characterise myocardial cell damage after orthotopic heart transplantation, concentration of circulating troponin T were measured prospectively in serial blood samples from 19 consecutive patients taken during the first three months after transplantation. RESULTS: Mean (SD) serum concentrations of cardiac troponin T reached a maximum of 3.6 (1.8) micrograms/l at 7.1 (4.2) days after transplantation and remained higher than 0.5 micrograms/l (twice the detection limit of the assay) in all patients for at least 43 days (mean (SD) 59 (20) days). There was considerable variation in cumulative troponin T release (area under the concentration curve) between the patients (ranging from 27 to 150 micrograms x days/l) that was not related to the total ischaemic time before transplantation or to the patient's renal or hepatic function, preoperative cardiac diseases, major histocompatibility complex matching or the number of complications related to rejection. CONCLUSIONS: Because the half life of cardiac troponin T serum is 2 h the current data show that antigen continued to be released from implanted hearts during the first postoperative months in quantities similar to minor Q wave myocardial infarction. Troponin T release after transplantation continued for much longer than after myocardial infarction or other cardiac surgery. Processes other than perioperative ischaemic damage must be responsible for the considerable individual differences in the release of cardiac troponin T. PMID- 8518062 TI - Permanent pacing after cardiac transplantation. AB - OBJECTIVE: To determine the need for long-term pacing and optimum mode of pacing in cardiac transplant recipients. DESIGN: (a) A retrospective review of patient records. (b) A prospective study of pacemaker use by 24 hour ambulatory electrocardiography before and after reprogramming to minimise use of pacemakers. SETTING: Outpatient clinic, supra-regional cardiopulmonary transplant unit. PATIENTS: All 21 patients at this centre who had received permanent pacemakers after cardiac transplantation. 18 of 19 survivors completed the prospective part of the study. MAIN OUTCOME MEASURE: The presence of pacing during a 24 hour ambulatory electrocardiographic recording (programming: 50 beats/min, rate sensor inactivated). RESULTS: 21 of 191 (11%) recipients surviving one month or more received permanent pacemakers. The indication was sinus node dysfunction in 13 (62%) and atrioventricular (AV) block in eight (38%). Patients who paced on follow up 12 lead electrocardiograms declined from 38% at three months to 10% at three years after transplantation. After programming to 50 beats/min only five of 18 (28%) patients paced during a 24 hour ambulatory recording. Four of 11 (36%) recipients who received pacemakers for sinus node dysfunction paced compared with one of seven patients (14%) paced for AV block. No patient who had a pacemaker before the 16th day after operation continued to pace whereas five of nine implanted later were used long-term. CONCLUSION: Only five of 18 (28%) patients with pacemakers continued to pace long-term. Continued pacing was more common in those with persistent sinus node dysfunction after the second week after operation but the need for long-term pacing was not predictable. PMID- 8518063 TI - Ionised magnesium and calcium in plasma from healthy volunteers and patients undergoing cardiopulmonary bypass. AB - OBJECTIVES: To measure the concentration of ionised magnesium, [Mg2+], and ionised calcium [Ca2+], in plasma from healthy volunteers and patients undergoing cardiopulmonary bypass (CPB). These measurements were carried out because there have been few reliable measurements of these values in healthy volunteers and no direct measurements in this patient group. PATIENTS AND METHODS: Dip cast ion selective electrodes were used to measure Mg2+, Ca2+, and H+ in plasma at 37 degrees C. These values were correlated with total metal concentrations, [Mg] and [Ca], plasma sodium [Na], and albumin concentrations found by standard techniques. Blood samples were taken from the patient group immediately before and after CPB and a further sample 24 hours later. RESULTS: In healthy volunteers the [Mg] was 0.86 (0.12) mM and [Mg2+], was 0.48 (0.06) mM, and the corresponding value for [Ca] was 2.34 (0.06) and for [Ca2+] 1.01 (0.13) mM. Values for [Mg], [Ca], and [Ca2+] have been reported by others and those quoted here are similar. In the CPB group the preoperative [Mg] was lower than the normal group but did not alter one hour after CPB and was slightly raised after 24 hours. The [Mg2+], however, was significantly reduced after 24 hours. Both [Ca] and [Ca2+] were slightly reduced after 24 hours but when adjusted for plasma albumin concentrations they were unchanged over this period. CONCLUSIONS: The most important finding is that around 24 hours after CPB the plasma [Mg2+] is significantly reduced, with no change to the total [Mg]. Corresponding changes to [Ca] and [Ca2+] were much smaller. This supposes the presence of an Mg2+ binding ligand of unknown origin in the plasma that may contribute to the cardiac arrhythmias that occur in some patients at this time after CPB. PMID- 8518064 TI - Berheim "a" wave: obstructed right ventricular inflow or atrial cross talk? AB - OBJECTIVE: To study the possible mechanisms underlying the dominant "a" wave in the jugular venous pulse seen in patients with left ventricular hypertrophy (Bernheim "a" wave). DESIGN: Prospective examination of the left ventricular transverse and longitudinal axes, transmitral and transtricuspid flows, and jugular venous pulse recordings. SETTING: Tertiary referral centre for cardiac disease. SUBJECTS: 23 patients with left ventricular hypertrophy of various aetiologies and a dominant "a" wave in the jugular venous pulse. Controls were 21 normal volunteers. RESULTS: Early diastolic filling of the right ventricle was normal. During right atrial systole the (mean(SD)) tricuspid ring motion was exaggerated (1.2(0.4) v 0.8(0.2) cm, p < 0.001) and Doppler A wave velocity slightly increased (0.3(0.1) v 0.2(0.08) m/s, p < 0.01), although the E wave remained dominant. By contrast left ventricular isovolumic relaxation time was longer than normal (70(20) v 55(10) ms, p < 0.001) with wall motion incoordinate in the septal long axis, 15%(9.5%) v 6.6%(3%) total excursion occurring before mitral valve opening. During early filling the extent of long axis motion was decreased to 0.6(0.5) cm from 1.1(0.2) cm, (p < 0.001) and 0.5(0.2) cm from 0.9(0.2) cm, (p < 0.0001) at the left and septal sites, and similarly its peak lengthening rate reduced to 5.4(2.5) cm/s from 10(3) cm, (p < 0.001) and 4.3(2.2) cm/s from 8(2) cm, (p < 0.001). The atrial component of long axis lengthening was increased to 43%(18%) from 29%(6%) (p < 0.01) and 55%(15%) from 33%(8%) of the total excursion (p < 0.0001). Left ventricular E/A ratio was less than normal (0.9(0.8) v 1.4(0.4), p < 0.05). CONCLUSIONS: There is no evidence of obstruction or any other disturbance of early diastolic right ventricular inflow in Bernheim's syndrome. It is possible that the haemodynamically appropriate increase in left atrial activity is mirrored on the right side due to shared interatrial myocardial fibres. This could represent a form of atrial interaction. PMID- 8518065 TI - Echocardiographic restenosis after successful balloon dilatation of the mitral valve with the Inoue balloon: experience of a United Kingdom centre. AB - OBJECTIVES: (a) To assess the echocardiographic incidence of restenosis after successful balloon dilatation of the mitral valve at a mid-term follow up of one year among a population of predominantly United Kingdom patients. (b) To identify any factors, assessed before or during dilatation, which may predict the development of restenosis. DESIGN: Successful dilatation of the mitral valve was defined as an increase in mitral valve area of > 25% and a final valve area of at least 1.5 cm2. Echocardiographic restenosis was defined at follow up as a loss of 50% of initial gain and a valve area of less than 1.5 cm2. Mitral valve area was assessed by transthoracic echocardiography before, during, 48 hours after, and one year after successful balloon dilatation of the mitral valve. Echo score before dilatation (an assessment of valvar and subvalvar calcification, thickening, and mobility), age, rhythm, echocardiographic mitral valve area before and after dilatation, left atrial pressure before and after dilatation, and end diastolic mitral valve gradient before and after dilatation were compared in those patients with and without echocardiographic restenosis at one year. SETTING: A regional cardiothoracic centre in the United Kingdom that performs 20 30 balloon dilatations of mitral valves each year. PATIENTS: 39 patients, with symptomatic dominant mitral stenosis, who had undergone successful balloon dilatation of the mitral valve, and in whom echocardiographic assessment of mitral valve area was available at one year. 92% of patients were citizens of the United Kingdom. INTERVENTIONS: Balloon dilatation of the mitral valve by the Inoue technique. MAIN OUTCOME MEASURES: Mitral valve area and patient symptom class (New York Heart Association) one year after successful dilatation of the mitral valve. RESULTS: The incidence of echocardiographic restenosis was eight of 39 patients (21%). Of the eight patients with restenosis four underwent mitral valve replacement, two had repeat dilatation of the mitral valve, and two remained on medical treatment. With univariant analysis, factors associated with restenosis were increased age, higher echo score before dilatation, and a lower mitral valve area immediately after the operation. The only independent risk factor for restenosis, shown by multivariant analysis, was a high echo score before dilatation. There was no significant fall in mitral valve area at one year in those patients without restenosis. Most (28/31) of these patients had echocardiographic evidence of splitting of at least one commissure after dilatation compared with only two of eight patients who developed restenosis. Of 10 patients with an echo score before dilatation > or = 10 only two had an initially successful operation and no restenosis at one year. CONCLUSIONS: The echocardiographic incidence of restenosis after dilatation of the mitral valve by the Inoue technique in patients of the United Kingdom is 21%. The principal factor associated with restenosis is a high echo score before dilatation. Increases in mitral valve area are maintained in those patients without restenosis and it is likely that the mechanism of initial increase in valve area is different in the two groups, being commissural splitting in those patients who do not get restenosis and valve stretching in those that do. In patients with an echo score > or = 10 dilatation of the mitral valve should be considered only as a palliative procedure. PMID- 8518066 TI - Early mobilisation after percutaneous cardiac catheterisation using collagen plug (VasoSeal) haemostasis. AB - OBJECTIVE: To assess the efficacy and safety of a haemostatic bovine collagen plug (VasoSeal) in reducing patient immobilisation after cardiac catheterisation from a percutaneous femoral arterial approach. DESIGN: A non-randomised, prospective analysis of a new biodegradable haemostatic agent on an intention to treat basis. SETTING: The catheterisation suite of a regional cardiothoracic unit. PATIENTS: A series of 63 patients having various diagnostic investigations and therapeutic interventions agreed to participate in this study. INTERVENTIONS: Cardiac catheterisation was performed from a percutaneous femoral artery approach. Patients taking aspirin and those who required formal anticoagulation were not excluded. Patients were measured for the appropriate sized collagen delivery system at the beginning of the procedure. At the end of the procedure two bovine collagen plugs were applied to the surface of the femoral artery through the channel created by the application device. MAIN OUTCOME MEASURES: Incidence of successful delivery, insertion time, immediate outcome, inpatient complications, success of mobilisation of the patient at one and two hours after the procedure, and whether these variables relate to individual patient characteristics. RESULTS: Successful placement of the device was achieved in 57 of 63 consecutive patients (90.5%). The mean (SD) insertion time was 86 (24) seconds. Six (9.5%) patients did not receive the haemostat because of femoral artery perforation by the tissue dilator (n = 3), inability to compress the femoral artery proximal to the site of delivery (n = 1), pre-existing haematoma (n = 1), or patient withdrawal from the study (n = 1). Uncomplicated mobilisation within two hours of investigation was possible in 54 of 57 (94.7%) patients receiving this device. A sizeable haematoma (> 5 x 5 cm) prevented early mobilisation in the remaining three patients. Mobilisation was uncomplicated in 32 of 34 (94.1%) patients mobilised at two hours and 22 of 23 (95.6%) at one hour (NS). One patient who was mobilised early without complication later developed evidence of claudication in the treated leg. Femoral arteriography showed a smooth intraluminal filling defect attached to the wall of the femoral artery at the puncture site. This obstruction, presumed to be a collagen plug, was treated successfully with angioplasty. Sheath size, arterial pressure, the use of aspirin, heparin or warfarin, and body mass index did not influence patient outcome. The pattern of complications did not relate to a learning curve experience. CONCLUSIONS: The bovine collagen haemostat is a relatively safe and effective device that allows far earlier patient mobilisation than conventional haemostasis after diagnostic and therapeutic interventions from a percutaneous femoral artery approach. These results have important implications for patients undergoing investigation in mobile x ray units or in hospital based day case units. PMID- 8518067 TI - Medium-term clinical results after the Senning procedure with haemodynamic and angiographic evaluation of the venous pathways. AB - OBJECTIVE: To assess the clinical condition of patients and the adequacy of their newly constructed venous pathways after the Senning operation for simple transposition of the great arteries. PATIENTS AND DESIGN: All 34 patients who had the Senning operation between March 1983 and December 1986 were reviewed. Survivors had detailed cardiac catheterisation studies one to two years later and clinical evaluation two to six years after surgery. RESULTS: There were two operative deaths (6%), one sudden late death (after two years), and 31 survivors (91%). No clinical evidence of obstructed venous pathways was found and there was no need for reoperation for any reason. The average mean (SD) pressure gradient at the junction of the superior vena cava and systemic venous atrium was 2.0 (1.7) mm Hg, although two patients had gradients of 7 mm Hg. The average gradient was 0.7 (1) mm Hg in the inferior vena caval pathway, and 1.4 (1.1) mm Hg between the mean pulmonary arterial wedge and pulmonary venous atrial pressures. Only the two patients with gradients of 7 mm Hg at the junction of the superior vena cava and the systemic venous atrium had considerable narrowing of the pathway and retrograde flow in the azygos vein to below the diaphragm. CONCLUSION: A small series of patients were comprehensively studied after the Senning operation for simple transposition of the great arteries. Scrupulous technique in the construction of the venous pathways has had excellent results with no need for reoperation for obstruction in either the systemic or pulmonary pathways. Clinical observation alone may fail to identify patients with venous pathway obstruction, therefore careful assessment is required, even in patients who are physically normal. PMID- 8518068 TI - Pulmonary vascular disease in neonates with transposition of the great arteries and intact ventricular septum. AB - BACKGROUND: Progressive pulmonary vascular disease in surgically unrepaired transposition of the great arteries with or without ventricular septal defect had been frequently described in the past. Occurrence of progressive pulmonary vascular disease has been reported even after atrial switch procedure done at three months of age. With the advent of neonatal surgical repair, this problem is virtually non-existent. There is a small subgroup of infants with transposition of the great arteries who show pulmonary vascular disease in the neonatal period that can adversely affect the surgical outcome. The clinico-pathological correlation in this group of patients was studied. OBSERVATIONS: Three patients, with transposition of the great arteries and intact ventricular septum, who showed histological evidence of pulmonary vascular disease in the neonatal period or early infancy are described. Two of these patients, continued to have poor systemic oxygenation despite adequate atrial communication. One patient had a close ductus arteriosus within the first two hours of birth while on prostaglandin E1 infusion. CONCLUSIONS: In the absence of left ventricular outflow tract obstruction, a poor response to atrial septostomy suggests pulmonary hypertension and pulmonary vascular disease. Antenatal constriction of the ductus arteriosus may contribute to such changes in pulmonary vasculature. PMID- 8518070 TI - Hypoplastic left heart syndrome with right aortic arch in a newborn. AB - A patient with the rare combination of a right-sided aortic arch in hypoplastic left heart syndrome with an incomplete vascular ring is described. PMID- 8518069 TI - Unmasking of left free wall ventricular preexcitation by His bundle ablation. AB - His bundle ablation was performed in a 48 year old man with drug refractory orthodromic atrioventricular reentrant tachycardia and paroxysmal atrial fibrillation. Reentry was caused by a left free wall concealed accessory pathway. Interruption of the His bundle by low energy direct current shock (25 J) was quickly followed by anterograde conduction via the accessory pathway, with various forms of advanced block. The combined effect of unfavourable anterograde conduction (prolonged anterograde effective refractory period and decremental conduction), the left lateral location of the accessory pathway and intra-atrial conduction delay on one side, and normal conduction via the atrioventricular node and His bundle with retrograde concealed conduction into the accessory pathway on the other side resulted in masking of the anterograde conduction capability of the anomalous pathway. This observation does not seem to invalidate the choice of His bundle ablation in similar cases. PMID- 8518071 TI - Restrictive cardiomyopathy caused by chloroquine. AB - A 59 year old white woman who had been treated with chloroquine phosphate for 25 years presented with signs of congestive heart failure and was diagnosed as having restrictive cardiomyopathy by non-invasive methods. Electron microscopy of a biopsy specimen of skeletal muscle showed lesions compatible with chloroquine myopathy. The patient died five weeks after presentation. Electron microscopy of heart tissue showed similar lesions to those of the skeletal muscle. PMID- 8518072 TI - Emergency percutaneous transluminal coronary angioplasty for intractable ventricular arrhythmias associated with acute anterior myocardial infarction. AB - A previously fit marathon-running 54 year old man was admitted as an emergency having collapsed with chest pain caused by an acute transmural anterior myocardial infarction. He was initially resuscitated by his general practitioner then had recurrent episodes of ventricular flutter and fibrillation requiring continuing cardiopulmonary resuscitation and repeated defibrillation. During ambulance transfer and in the hospital emergency department he received appropriate intravenous antiarrhythmic drug treatment and a total of 63 transthoracic DC shocks, with good cardiac output between shocks. After his condition failed to stabilise in intensive care, an intra-aortic balloon pump was inserted and coronary angiography showed a proximal occlusion of the left anterior descending branch. Coronary angioplasty successfully re-opened the vessel with an excellent angiographic result. The intra-aortic balloon pump was withdrawn the following day and he was well enough to be discharged 7 days later. At 4 weeks he performed a satisfactory maximal exercise test and remains in New York Heart Association functional class I. PMID- 8518073 TI - Mycotic aneurysm of left subclavian artery. AB - Bacterial endarteritis is rare and usually affects the abdominal aorta. A case of bacterial left subclavian arteritis complicated by mycotic aneurysm is presented. An early diagnosis of infective arteritis was made based on a history of fever, sweats, rigors, and a progressive macular rash, polyarthralgia splinter haemorrhage (limited to the left arm), and a loud left subclavian bruit on admission. A mycotic aneurysm was diagnosed by computed tomography and treated surgically. In cases of endarteritis the possibility of a mycotic aneurysm should be borne in mind even when there is no evidence of endocarditis. PMID- 8518074 TI - Acute pulmonary artery thromboembolism treated with thrombolysis: diagnostic and monitoring uses of transoesophageal echocardiography. AB - The central pulmonary arteries and any thrombus within them can be imaged by transoesophageal echocardiography. Its use is reported in the diagnosis and subsequent management of a patient with acute pulmonary embolism, whose response to thrombolytic treatment was monitored by further transoesophageal studies. Transoesophageal echocardiography may be a valuable primary diagnostic procedure in patients who seem to have sustained a significant pulmonary embolus and require urgent intervention. PMID- 8518075 TI - Quality of life in cardiovascular disease. PMID- 8518076 TI - Accelerated graft atherosclerosis after heart transplantation. PMID- 8518077 TI - A characteristic continuous wave Doppler signal in cor triatriatum? PMID- 8518078 TI - Propionibacterium acnes causing perivalve abscess. PMID- 8518079 TI - Tension-free repair of inguinal and aponeurotic hernias. PMID- 8518080 TI - [Alkaline esophagitis following total gastrectomy]. AB - Two cases of severe alkaline esophagitis following total gastrectomy, respectively for a gastric sarcoma and a gastric carcinoma, are reported. In the first case digestive continuity was assured through an Omega loop esophagojejunostomy, while in the second one an esophagojejunostomy according to the Moricca technique was performed. Both patients underwent reoperation and a conversion in Roux-en-Y esophagojejunostomy resolved the reflux related problems. The Authors, therefore, confirm Roux-en-Y esophagojejunostomy as the procedure of choice in preventing and curing esophagitis, which can seriously affect the quality of life and nutritional status of gastrectomized patients. PMID- 8518081 TI - [Infection of the vascular prosthesis. The diagnostic, preventive and treatment protocols: preliminary results]. AB - A number of strategies for the management of vascular graft infections are described in literature. Nevertheless, this serious compliance is still burdened with high rates of morbidity and mortality. At the present the principal efforts are therefore directed towards prevention and early diagnosis. In this view, the authors propose their protocol of study, on the basis of the encouraging results till now obtained. PMID- 8518082 TI - [Esophagojejunal anastomoses following total gastrectomy: manual and mechanical sutures compared]. PMID- 8518083 TI - [Primary muscular echinococcosis: a clinical case]. AB - Muscular localization of echinococcosis is considered unusual. The authors report a case of such uncommon hydatid localization. Pathogenetic hypotheses are discussed. PMID- 8518084 TI - [The use of staplers in intestinal surgery]. PMID- 8518085 TI - [Lymphoma of the residual gastric stump]. AB - The authors report a case of non-Hodgkin's lymphoma (lymphoplasmocytoid type) arisen on the gastric stump of a patient operated 18 years before according to Billroth II gastric resection for peptic ulcer. They underline the extraordinary rarity of the event because this type of neoplasia never arises on the gastric stump, where would be more likely to find, due to irritative chemical stimuli of the biliary reflux, phenomena of intestinal metaplasia or severe dysplasia highly predisposing to adenocarcinomas. Furthermore, they stress the importance of a "deep" bioptic examination for a diagnosis as early as possible of this type of pathology. PMID- 8518087 TI - [The role of echography in assessing abdominal trauma: the experience of 1750 cases]. AB - The authors report their experience of 1750 ultrasonic examinations of the abdomen performed in emergency, showing the value and usefulness of echo-scans in the evaluation of abdominal traumas. Easy and quick to perform, it permits an accurate diagnosis with a low ratio of error. Particularly, ultrasonography gives the chance to operate in emergency patients with steady haemodynamic conditions and to follow up those with partial parenchymal lesions, monitoring the clinical status in order to properly choose between conservative treatment and delayed surgery. PMID- 8518086 TI - [The use of totally implantable systems (TIS) for long-term endovenous therapy]. AB - The availability of a long-term central venous access for the management of neoplastic and chronic patients is extremely important in order to achieve an easy and safe infusion of chemotherapeutic drugs, blood components, and parenteral nutrition. The authors evaluated 26 adult patients (25 with malignant tumors and 1 with severe asthma) in whom implantable catheter systems were placed subcutaneously between February 1989 and March 1992. Catheters were inserted through the cephalic vein in 13 cases, the subclavia vein in 8 cases and jugular vein in 5 cases. The mean function time was 262 days in deceased patients and 155 in alive ones. There were no infective or thromboembolic complications. The authors, in agreement with the literature, confirm that TIS represent a safe and easy access for a long term i.v. therapy, with a very low complication rate. Furthermore, comfort of the patients is substantially improved and nursing care is greatly facilitated. PMID- 8518088 TI - 3-month-old baby presents in acute renal failure, edematous, and with generalized convulsions. PMID- 8518089 TI - Major histocompatibility complex genetic studies in renal disease. PMID- 8518090 TI - What is known about renal replacement therapy in a child with Down's syndrome? PMID- 8518091 TI - Long-term ciclosporin treatment in children with steroid-dependent nephrotic syndrome. AB - We report the effect of 18-month ciclosporin (CS) treatment in 19 children with steroid-dependent frequently relapsing nephrotic syndrome. CS was started at 3-5 mg/kg per day after remission with steroid therapy, was adjusted to maintain a trough blood level of between 200 and 600 ng/ml and was administered for 6 months (high-dose CS). Then, the dosage of CS was decreased and 2.5 mg/kg per day was administered for the subsequent 12 months (low-dose CS). Only 2 patients had relapses during the initial 6 months of CS therapy. Eight patients had infrequent relapses, 4 had frequent relapses and 7 had no relapses during the 12 months of low-dose CS. Not only did continuation of CS at a lower dosage decrease the relapse rate, it also reduced steroid toxicity, allowed increased growth in 16 of the 19 patients and also decreased obesity scores in 12 of these patients. All of the side-effects that occurred during the 18-month period of CS treatment were reversible and none was serious enough to necessitate discontinuation of therapy. Our 18-month CS treatment was helpful in preventing relapses and reducing steroid toxicity in children with steroid-dependent frequently relapsing nephrotic syndrome. PMID- 8518093 TI - Renal parenchymal malakoplakia--a case report and review of the literature. AB - Malakoplakia is an inflammatory condition associated with persisting bacterial antigen in macrophages and characterized histologically by the Michaelis-Gutmann body, containing bacterial fragments. We review the pathogenesis of malakoplakia and report a novel form of treatment successfully used in an 8-week-old infant with bilateral renal malakoplakia. The patient presented with an acute Escherichia coli urinary tract infection and enlarged kidneys. Antibiotic regimes were ineffective, but once the diagnosis was made treatment was changed to an immunosuppressive regime of prednisolone and azathioprine, to which she responded promptly. Renal malakoplakia should be considered in any patient with a urinary tract infection unresponsive to antibiotics and enlarged kidneys. Although a large proportion of patients with malakoplakia have an underlying systemic disorder, which may account for their abnormal macrophage function, the rest demonstrate either an isolated macrophage defect or no detectable anomaly at all. It is in this latter group we suggest that an immunomodulating regime can be curative. PMID- 8518092 TI - Renal cysts in the carbohydrate-deficient glycoprotein syndrome. AB - The carbohydrate-deficient glycoprotein (CDG) syndrome is a newly described genetic disorder with autosomal recessive inheritance and multiple organ involvement. We describe five patients with the CDG syndrome who all had abnormal renal structure. In two patients autopsy disclosed multiple microcysts. A hyperechogenic pattern strongly suggesting microcysts was demonstrated in all patients that were available for ultrasound examination, while a large single cyst was also seen in one patient. Based on these findings and the reports of others, renal cysts appear to be common in the CDG syndrome. PMID- 8518094 TI - Evaluation of OKT3 monoclonal antibody and anti-thymocyte globulin in the treatment of steroid-resistant acute allograft rejection in pediatric renal transplants. AB - We reviewed the effectiveness of Muromonab-CD3 (OKT3) and anti-thymocyte globulin (ATG) in the treatment of corticosteroid-resistant acute renal allograft rejection in 49 transplanted children. Reversal of rejection was successful in 22 of 23 patients (96%) treated with OKT3 and 21 of 26 (81%) treated with ATG (P = NS). Re-rejection episodes occurred within 1 month of cessation of therapy in 9 of 22 patients treated with OKT3 but only in 2 of 21 who received ATG (P < 0.05). In the patients with re-rejection, 7 of the 9 patients originally given OKT3 and 1 of the 2 who received ATG responded to a repeat course of high-dose corticosteroids; thus, at 1 month post treatment, the incidence of graft loss due to initial rejection or re-rejection was 13% for the OKT3 and 23% for the ATG group (P = NS). Graft survival was similar at 6 months: 82% for OKT3- and 73% for ATG-treated patients (P = NS); 100% patient survival was noted in both groups. Mean calculated creatinine clearance prior to, during, and at 1 and 6 months post rejection was similar in the OKT3- and ATG-treated groups. Neutropenia and thrombocytopenia occurred more frequently in the ATG group, but there was no significant difference in infectious complications. Two patients developed high (> or = 1:1,000) OKT3 antibody titers. In our experience, children with corticosteroid-resistant acute renal allograft rejection treated with OKT3 and ATG had similar allograft survival and level of renal function at 1 and 6 months, and number of infectious complications post therapy. PMID- 8518095 TI - Anti-OKT3 response following prophylactic treatment in paediatric kidney transplant recipients. AB - The anti-OKT3 response was studied in 40 paediatric kidney transplant recipients receiving OTK3 as a prophylactic treatment in association with azathioprine and prednisone. Only 1 patient experienced a reversible acute rejection episode while receiving OKT3. OKT3 induced a rapid disappearance of CD3+ cells, but significant proportions of CD3+ cells reappeared before the end of the treatment in 14 patients. Wide variations in circulating OKT3 levels were observed and in only 50% of patients could stable circulating OKT3 levels be detected until discontinuation of treatment. Anti-OKT3 antibodies detected by the enzyme-linked immunosorbent assay (ELISA) (anti-idiotypic and anti-isotypic antibodies) developed in 91% of patients. Anti-idiotypic antibodies detected by the immunofluorescence inhibition test were found in the sera of 71% of patients, always when high titres of anti-OKT3 antibodies were detected by ELISA. As it has recently been shown that anti-idiotypic antibodies are associated with failure of subsequent OKT3 treatment, we conclude that OKT3 should be restricted to steroid resistant rejection crises in paediatric patients. PMID- 8518096 TI - The fractional excretion of urea: a new diagnostic test for acute renal allograft rejection. AB - Fractional excretion of sodium (FENa) has been used in the diagnosis of acute renal allograft failure on the assumption that poor allograft perfusion should result in a low FENa. However, many patients receive medications which affect the active transport of Na+ and thus FENa. In contrast, the fractional excretion of urea (FEurea) is mostly dependent on passive forces and is therefore less influenced by drug therapy. To test the hypothesis that FEurea might be more useful than FENa in evaluating graft failure, we compared FEurea with FENa during 79 episodes of acute renal allograft dysfunction due to acute rejection (AR), cyclosporine nephrotoxicity (CsA-Nx), viral infection, or bacterial infection in 32 children and young adults with renal transplants. There was no significant difference between groups in FENa. However, FEurea was significantly lower (P < 0.05) in patients with CsA-Nx (32.6 +/- 1.9%) and viral infection (32.9 +/- 3.2%) than those with AR (45.1 +/- 1.7%) or bacterial infection (38.9 +/- 2.5%). FEurea was < 35% in 20 of 28 (71.4%) episodes of CsA-Nx and 8 of 11 (72.2%) of viral infection, but only 5 of 36 (13.9%) of AR (P < 0.05). FEurea was also measured during stable graft function, 7-14 days prior to allograft dysfunction. CsA-Nx was associated with a 30.5 +/- 8.3% decrease in FEurea. FEurea did not change in patients with AR. Based on these findings, we present an algorithm to aid in the differential diagnosis of acute renal allograft failure. PMID- 8518097 TI - End-stage kidneys are capable of increased erythropoietin production. AB - A relative deficiency of erythropoietin (EPO) is the most important factor responsible for the anaemia of end-stage renal failure. Patients on continuous ambulatory peritoneal dialysis usually maintain a higher haemoglobin concentration than patients on other forms of dialysis. The precise mechanism is uncertain, and there is disagreement over the role of increased EPO production. An 11-year-old boy with end-stage renal failure maintained on overnight cycling peritoneal dialysis developed a reticulocytosis, followed by a marked increase in haemoglobin concentration, shortly after his dialysis schedule was altered to include a full peritoneal cavity during the daytime. This improvement in erythropoiesis was closely associated with an increase in serum EPO concentration. We suggest that the alteration in dialysis may have resulted in enhanced clearance of an inhibitor of EPO production and discuss the possible mechanisms involved. PMID- 8518098 TI - Recombinant erythropoietin (Epogen) improves cardiac exercise performance in children with end-stage renal disease. AB - To determine the effects of anemia in children with end-stage renal disease, we studied cardiac performance before and 1 and 6 months after recombinant erythropoietin (Epogen). Children with end-stage renal disease were included if they had significant anemia [hematocrit (Hct) < 30%]. Epogen 50 U/kg was given subcutaneously or intravenously three times per week until the Hct was > or = 33%. Echocardiography, cardiac output (acetylene rebreathing), and treadmill (modified Bruce) tests were performed. Boys (9) and girls (9), 11.9 +/- 5.6 years, were given Epogen and the Hct increased (from 21.7 +/- 2.7% to 33.4 +/- 2.1%, P = 0.001). Heart rate decreased (P = 0.04) and stroke volume did not change. Blood pressure did not change. Cardiac thickness, chamber dimensions, left ventricular wall stress, velocity of circumferential fiber shortening, and indices of diastolic function were normal and did not change after Epogen. Exercise time increased (from 10.3 +/- 1.9 to 11.2 +/- 1.9 min, P = 0.01) after 1 month of Epogen. Resting oxygen consumption (VO2) decreased (from 7.8 +/- 1.8 to 6.9 +/- 1.4 ml/min per kg, P = 0.01) 1 month after Epogen and peak exercise VO2 did not change after Epogen. There were no differences in exercise tests between the 1 and 6 month measurements. Exercise tolerance improves after the short-term correction of anemia and there is no further improvement after long-term correction. PMID- 8518099 TI - Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis. AB - Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5 +/ 0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5 +/- 0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients. PMID- 8518100 TI - Measurement of peritoneal dialysis delivery in children. AB - We measured urea [weekly urea clearance/total body water (KT/Vurea)] and creatinine (CCr) clearances on 35 occasions in 15 stable chronic peritoneal dialysis patients to determine the feasibility and reproducibility of such measurements in children. In addition, we performed peritoneal equilibration tests (PETs) to characterize our patients' peritoneal membranes and to estimate weekly clearances. We demonstrated that dialysis delivery can be quantified by these standard measurements in children of widely varying size. Further, we found that clearances predicted from PET data were similar to measured values in all patients. However, predicted and measured values were most significantly correlated in patients with high and high-average peritoneal membrane permeability. KT/Vurea and CCr were correlated overall, but differences in scaling affected the validity of the relationship. When both clearances were scaled to weight, the correlation was closer, but still differed between PET determined peritoneal membrane types. PMID- 8518101 TI - Equilibration testing: close, but not quite right. PMID- 8518102 TI - Acute renal failure after exercise in a child with renal hypouricaemia. AB - We describe a 12-year-old boy with renal hypouricaemia who presented with acute renal failure after a 6-h sports training session. Back and loin pain were noted at presentation. Although serum creatinine and blood urea nitrogen were elevated, the serum uric acid concentration was normal (2.6 mg/dl). This decreased to 0.3 mg/dl after recovery. The pyrazinamide and probenecid tests revealed that the cause of renal hypouricaemia in this patient was totally defective uric acid reabsorption. Acute renal failure after exercise is a rare but serious complication in paediatric patients with renal hypouricaemia. PMID- 8518103 TI - Hyperechoic kidneys in the newborn and young infant. AB - Increased echogenicity of the kidney in the newborn has many causes, some of which reflect serious renal disease. The major abnormal imaging pattern is the large, diffusely hyperechoic kidney with abnormal architecture. Its differential diagnosis includes recessive and dominant polycystic kidney disease (PKD), glomerulocystic kidney disease, and diffuse cystic dysplasia. The family history and ultrasonic screening of the parents and siblings are essential in the evaluation. The identification of associated nonrenal abnormalities is important to the recognition of syndromal cystic disease. Glomerulocystic kidney disease, which comprises sporadic and syndromal forms, appears similar to dominant PKD. While renal biopsy almost always differentiates recessive from dominant PKD, renal biopsy cannot differentiate among the forms of glomerulocystic kidney disease, except in the case of tuberous sclerosis, which has unique histopathological characteristics. Other causes of the enlarged hyperechoic kidneys with abnormal architecture include renal vein thrombosis and congenital nephrotic syndrome. A second pattern is the hyperechoic small kidney with abnormal architecture. Many of these kidneys are dysplastic and associated with urinary tract obstruction. The combination of hyperechoic parenchyma and pyelocaliceal dilatation suggests obstructive cystic dysplasia. Cortical and medullary necrosis in the newborn also causes hyperechogenicity in small kidneys. A third pattern contains those kidneys with medullary hyperechogenicity, the most common cause of which in the newborn is nephrocalcinosis associated with furosemide therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518106 TI - Clinical quiz. Thirteen month old child presented with osteopenia and rickets. PMID- 8518104 TI - Pathogenesis of idiopathic IgA nephropathy. AB - Despite a prodigious amount of work on the physiology of IgA production in man, and many studies on the immunopathology of IgA nephropathy, ranging from the immunogenetics to the immune response to chemical characteristics of the IgA, we are hardly any nearer to defining the pathogenesis of this disease. One of the main changes in our understanding has been to recognise that the bone marrow, now known to produce normally one-third of the body's IgA, overproduces this immunoglobulin in IgA nephropathy. This alters the previous notion that IgA nephropathy was due simply to IgA production in the mucosa, although a mucosal component is not excluded. Certain characteristics of the IgA in the diseased kidney and the circulation have been defined: it is of subclass IgA1 and has a higher proportion of lambda light chains and negative charge than in normal subjects. The specificities of the IgA, either in the kidney or in complexes, have not helped to clarify the pathogenesis. They have been found for a wide range of endogenous and exogenous antigens, suggesting that the antibody activity represents polyclonal B cell activation. These findings have not helped to confirm the prevailing theory that IgA nephropathy is an immune complex disease. Other theories put forward are that IgA nephropathy is an autoimmune disease, glomerular components or IgA itself being among the candidate antigens, or that there is primary dysregulation of the IgA immune system. At this stage of development in our understanding of this common nephropathy, it is important to guard against the assumption that idiopathic IgA nephropathy is one disease and is the result of a single pathogenetic mechanism. PMID- 8518105 TI - Renal adaptation to phosphate deprivation: lessons from the X-linked Hyp mouse. AB - The X-linked Hyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutant Hyp mice differs from that of normal littermates. While Hyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodium-phosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts, Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] that can be ascribed to increased renal 1,25(OH)2D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed in Hyp mice is also apparent in X-linked Gy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)2D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)2D-dependent increase in overall tubular phosphate conservation. PMID- 8518107 TI - Clinical quizzes on acid-base problems. PMID- 8518108 TI - Acute renal failure due to interstitial nephritis associated with Yersinia pseudotuberculosis infection. PMID- 8518109 TI - The Tenckhoff catheter in acute renal failure. PMID- 8518110 TI - Interferon treatment of hepatitis B-associated membranous glomerulonephritis and nephrotic syndrome. PMID- 8518111 TI - Effects of the development of modern vascular services on amputation rates in Leicester, U.K.: a preliminary report. AB - We have reviewed 3036 consecutive patients who underwent arterial reconstruction, percutaneous transluminal angioplasty, or a major amputation for lower limb peripheral vascular disease in Leicester between 1974 and 1990. Patient data were obtained from the Hospitals Activity Analysis database, which codes all patient discharges according to diagnosis and treatment. During this 17-year study period, 1132 patients have undergone arterial reconstruction, 706 patients have undergone percutaneous transluminal angioplasty, and 1198 patients have undergone major amputation. The results show that the number of arterial reconstructions and angioplasties for lower limb arterial occlusive disease has increased over the last 17 years. The total amputation rate has decreased slightly during the period studied, but overall the decrease has not been significant. PMID- 8518112 TI - Acute and chronic upper extremity ischemia. I. Large vessel arterial occlusive disease. PMID- 8518113 TI - Abnormal wall strain at distal end-to-side anastomoses. AB - Cyclic stretch has been demonstrated to induce proliferative and secretory activities by cultured arterial endothelial and smooth muscle cells, cellular processes that contribute to the development of intimal hyperplasia. A model of an end-to-side anastomosis was developed to examine the hypothesis that regions of the artery at such anastomoses are subjected to focally increased cyclic stretch, which may stimulate the development of intimal hyperplasia. Polytetrafluoroethylene grafts were anastomosed end to side to latex rubber tubes that have elastic properties similar to those of the human femoral artery. Pulse waves with physiologic pressure, rate, and contour were applied, and systolic and diastolic diameters were measured in two planes at longitudinal intervals. Circumferential strain imposed on the latex "artery" was calculated at each interval. Strain imposed perpendicular to the suture line was also measured. Circumferential strain was consistently maximal at a distinct region of the "artery" along the proximal third of the anastomosis (6.0 +/- 1.1% vs. 3.3 +/- 0.5% at other regions of the "artery"). The maximal strain across the suture line was found at precisely the same region (3.9 +/- 0.3% vs. 2.0 +/- 0.4%). The anastomotic region of the recipient artery in a distal end-to-side anastomosis is subjected to cyclic circumferential strains two times greater than those experienced by the remainder of the artery. This corresponds to a common location of intimal hyperplasia. Such strains may be a stimulus for intimal hyperplasia. PMID- 8518114 TI - Analysis of balloon dilatation of human vein graft stenoses. AB - Controversy continues as to whether percutaneous transluminal angioplasty (PTA) or surgical revision is the ideal modality for the treatment of failing grafts. This prompted a histopathologic analysis of failing human vein graft segments subjected to ex vivo balloon dilatation to define variables responsible for the discrepant results. Fifteen vein graft lesions from 14 patients with failing infrainguinal bypasses were recovered after surgical excision. Each graft lesion was focal and uniform in length (2.1 +/- 0.3 cm). Rings sectioned from adjacent regions of each vein graft lesion before and after balloon inflation were processed for histologic study, photomicrography, and image analysis. Angioplasty balloon size was selected on the basis of preoperative arteriograms. Graft lesions were divided into three groups based on lesion thickness and the degree of fibrosis and cellularity seen on sections stained with Masson's trichrome. The luminal area before angioplasty was not significantly different for the three groups (p > 0.2). Vein grafts with thick intimas (group 1) had significantly less luminal dilatation after angioplasty as compared with less thick intimal lesions (groups 2 and 3; p < 0.001). Those lesions with varying degrees of cellularity (groups 2 and 3) showed no significant differences in luminal diameter after angioplasty. However, the cellular lesions in group 2 consistently formed multiple intimal flaps that could produce PTA failures even with good luminal restoration. The varying histology of vein graft lesions and associated differences in intimal thickness and cellularity may be responsible for the inconsistent results following PTA. Estimates of wall thickness before angioplasty, particularly in the intimal area, may be helpful in evaluating which lesions might benefit most from PTA. PMID- 8518115 TI - Local infusion of fibrinolytic agents for acute renal artery thromboembolism: report of ten cases. AB - Management of acute renal artery occlusion remains a therapeutic challenge. We report our experience with 10 cases of acute renal artery occlusion treated primarily by local infusion of fibrinolytic agents. Renal artery occlusion occurred as a result of thrombosis of a stenosed vessel in three cases, from renal artery embolism in two cases, as a complication of percutaneous transluminal angioplasty in four cases, and in association with aortic occlusion in one case. Flank pain was present in all cases and hematuria in four cases. Acute renal failure was seen at the time of presentation in four cases (one case from bilateral occlusion and three cases from an associated nonfunctioning contralateral kidney). Diagnosis was confirmed by renal isotope scanning and arteriography in all cases. All patients were treated by selective infusion of streptokinase or urokinase into the occluded renal arteries. In five cases this was combined with balloon catheter angioplasty. Therapy was initiated within 24 hours from the onset of symptoms in three cases, within 3 days in four cases, within 6 days in two cases, and after 5 weeks in one case. Successful revascularization was initially achieved in 7 of the 10 cases by arteriographic criteria. Rethrombosis occurred in one patient after 3 days and fibrinolytic therapy was repeated successfully. Renal function was restored in one of the four patients presenting with acute renal failure. One complication necessitating resection occurred as a result of fibrinolytic therapy in the form of acute mesenteric embolism with descending colon infarction. No major bleeding complications were encountered and there were no deaths in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518116 TI - Silent myocardial ischemia is not predictive of myocardial infarction in peripheral vascular surgery patients. AB - Continuous ambulatory ECG (CAECG) monitoring has been advocated as an effective low-cost preoperative method for detecting silent myocardial ischemia in patients undergoing peripheral vascular surgery. In addition, silent ischemic events are associated with an increased incidence of postoperative myocardial infarctions. Ninety-six patients (mean age 73 years) admitted for elective aortic (24) or infrainguinal (72) operations over a 2-year period underwent 24-hour two- or three-lead CAECG monitoring. Results were reviewed by a single cardiologist blinded to the study. The criterion for ischemia was ST segment depressions of 1 mm or greater for 40 seconds or more 60 msec after the J point. Postoperative myocardial infarction was determined by ECG changes and/or elevated serum creatinine phosphokinase with positive MB isoenzymes. Risk factors included hypertension (71%), history of coronary artery disease (66%), smoking (61%), and diabetes mellitus (47%). Nine out of 96 patients (9.4%) had a positive CAECG test for silent myocardial ischemia. Only one patient (11.1%) developed postoperative myocardial infarction and there were no deaths in this group. The incidence of postoperative myocardial infarction in the nonischemic group was 16.1% (14/87). However, the mortality in this group was 6.9% (6/87). New and malignant arrhythmias requiring preoperative medical intervention were observed in seven patients (7.4%): two cases of ventricular tachycardia and five cases of atrial flutter/fibrillation. Contrary to previous reports, CAECG monitoring for silent ischemia was not a significant predictor of postoperative myocardial infarction or mortality in our patient population. However, we continue to recommend the preoperative use of CAECG monitoring as a diagnostic tool for unsuspected malignant arrhythmias. PMID- 8518117 TI - Intraoperative B-mode ultrasonography is a useful adjunct to peripheral arterial reconstruction. AB - We used an ultrasound imaging system with a 10 MHz probe during 118 vascular procedures. These procedures included 56 cerebrovascular, 38 infrainguinal, 16 renal, 4 mesenteric, and 4 aortic reconstructions. In 29 procedures, intraoperative ultrasonography was used to supplement or replace preoperative arteriography to better define the extent of disease for the optimal placement of an anastomosis or to determine the need for an additional reconstructive procedure. In 106 cases, ultrasonography was used for postreconstruction assessment. Of the 21 (20%) defects found, 11 (10%) were deemed important enough to warrant correction. Defects were significantly more common following endarterectomy procedures (p < 0.01). All 11 of the major defects were successfully repaired, and neither the corrected defects nor the 10 uncorrected minor defects were associated with postoperative complications. Patients (with and without defects) underwent routine early postoperative follow-up assessment of the technical adequacy of their reconstruction using color duplex imaging; no residual defects were discovered. Two (2%) postoperative occlusions (one femorofemoral and one aortorenal bypass) occurred without a technical defect noted on reexploration. This clinical experience demonstrates that B-mode ultrasonography can supplement or replace preoperative arteriography in selected cases and is a valuable technique for identifying defects intraoperatively so that they can be immediately corrected. PMID- 8518118 TI - Differences in carotid shunt flow rates and implications for cerebral blood flow. AB - A wide variety of carotid shunts are available for use in extracranial carotid surgery. Since it is commonly assumed that when properly positioned all shunts are equal in ability to protect the brain from cerebral ischemia, the choice of shunt is usually based on handling characteristics. However, after an intraoperative stroke occurred in a patient, we compared shunt flow rates using a simple and reproducible method of measurement. A mock circuit was created using a saline-filled fluid reservoir connected to the particular shunt being tested via 1/2-inch tubing. Hydrostatic pressure across the shunt was varied by changing the height of the reservoir, and the flow was collected over 30-second intervals. Multiple flow rate measurements were performed for each shunt with pressure gradients varying from 25 to 150 cm H2O. The data show significant hemodynamic differences among commercially available carotid shunts. A pressure gradient of 75 cm H2O produced a 2.8-fold variation in the amount of fluid delivered by various shunts. Minimal cerebral blood flow requirements and the possibility of underperfusion require that the surgeon consider such data in choosing an appropriate carotid shunt. PMID- 8518119 TI - Prospective evaluation of magnetic resonance imaging in the management of acute diabetic foot infections. AB - Infectious complications of the foot are a major cause of morbidity and mortality in diabetic patients. This prospective study evaluated the ability of MRI to adequately direct the medical and surgical management of 41 diabetic patients with acute foot infections. Forty-seven MRI scans of the foot in question were performed and classified as consistent with osteomyelitis, abscess, cellulitis or diffuse soft tissue infection, or any combination of these. Twenty-seven scans were negative or showed ill-defined soft tissue infection, or superficial cellulitis. Nineteen of these infections were treated nonoperatively and 17 resolved without surgical intervention. MRI was unsuccessful in directing management in one patient in whom an abscess spontaneously drained but was not seen on an MRI scan 4 days earlier. Eight scans revealed focal osteomyelitis and all eight of these patients were successfully managed with one operation. MRI showed a focal abscess in 12 patients, and adequate drainage was achieved without excessive disruption of uninvolved tissue planes in 11 of these patients. The remaining patient required a major amputation from the outset. Based on clinical outcome during the acute hospitalization period, operative findings, and/or pathologic confirmation, the positive predictive value of MRI in defining infectious pathology in the foot was 100% in this series of 20 positive scans. The negative predictive value of MRI was 96%. On the basis of this experience, we conclude that MRI is a diagnostic modality particularly well suited to evaluate acute diabetic foot infections and reliably aids in the management of acute infection to avoid exploration and debridement of uninvolved tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518120 TI - Vena cava replacement for malignant disease: is there a role? AB - Resection and graft replacement of the vena cava for malignant disease is rarely performed, often because of the advanced tumor stage. Since August 1987 we have selectively performed caval replacement in conjunction with tumor resection in 11 patients. Three patients had superior vena cava reconstruction (SVCR) and eight had inferior vena cava replacement (IVCR). There were six males and five females whose mean age was 59.3 years (range 24 to 75 years). Two patients, each with superior vena cava obstruction, presented with symptoms from venous compression. Malignancies involving the superior vena cava were thyroid carcinoma in two patients and lymphoma in one. Cancers requiring IVCR were leiomyosarcoma in three patients, cholangiocarcinoma in two, and malignant fibrous histiocytoma, hepatocellular carcinoma, and colon carcinoma metastatic to the liver in one each. All IVCRs and two SVCRs were performed with expanded polytetrafluoroethylene grafts. The remaining SVCR was constructed with spiral saphenous vein. Six IVCRs involved replacement of the retrohepatic inferior vena cava in conjunction with major liver resection. Mean intraoperative blood transfusions were 5.3 units (range 0 to 10 units). There were no operative deaths. Complications occurred in four patients and included postoperative bleeding in two, myocardial infarction in one, and wound infection in one. There were no perioperative graft occlusions, but one patient developed graft occlusion 2 months after SVCR. All IVCR grafts have remained patent (mean follow-up of 8.8 months). Two patients with SVCRs have died from recurrent cancer at 3.2 and 3.4 years postoperatively. Six patients with IVCRs have developed tumor recurrence either locally (n = 1), at a distant site (n = 2), or both (n = 3). Importantly, eight of nine survivors have an excellent performance status. We conclude that vena cava reconstruction for malignancy can be performed safely, has few graft related complications, and in some patients may offer the only possibility for tumor control. PMID- 8518121 TI - Progression of occlusive disease following femorofemoral crossover bypass graft. AB - Progression of distal disease is considered the most common cause of femorofemoral artery crossover bypass graft (FFBPG) failure. Twenty-seven patients with patient grafts (mean 53 months) were evaluated with segmental Doppler and duplex scan arterial studies for evidence of disease progression. In the early postoperative period (compared with preoperative levels), 26 patients (95.3%) showed a significant improvement (> 0.1) in the recipient limb ankle brachial index (ABI) (mean increase of 0.38; SD = 0.24) and/or ankle spectral arterial waveform. However, there was a statistically significant decrease (p = 0.0001) in the donor limb ABI, and 12 patients (44.4%) had a > 0.1 deterioration. On long-term follow-up (compared with preoperative levels) this difference was no longer significant (p = 0.49); only seven donor limbs remained with a > 0.1 decrease in ABI. The recipient limbs maintained a significant improvement (> 0.1) in the ABI compared to preoperative levels (p < 0.0001; mean of 0.39; SD = 0.16) except for three limbs that had decreased by 0.1. However, eight patients (29.6%) developed an increase in their donor common femoral artery acceleration time > 133 msec and/or increased blood flow velocity without a simultaneous significant decrease in their recipient limb ABI. In the latter group the preoperative donor limb common femoral artery acceleration time and ABI and the immediate postoperative change in donor limb ABI were not significantly different (p > 0.05) than in the remaining patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518122 TI - Neurologic events following carotid endarterectomy: prediction of outcome. AB - A total of 1572 carotid endarterectomies were performed at one institution between 1975 and 1987. One hundred five patients had early (< 3 weeks) neurologic events following carotid endarterectomy. Sixty-five patients had cerebral vascular accidents (CVAs) (4.1%), 14 patients had reversible ischemic neurologic deficits (0.9%), and 26 patients had transient ischemic attacks (1.7%). Eight patients died from CVAs (0.5%). The mean follow-up was 31 months (range 1 to 137 months) with a 5-year cumulative survival of 77%. The median time of occurrence of neurologic events was 4 hours. Ages, cerebral protection, patches, carotid occlusion time (mean 29 minutes), gender, and status of the contralateral carotid arteries were not predictors of outcome. Death from neurologic events increased significantly in patients who had preoperative CVAs compared with patients with preoperative transient neurologic deficits (p < 0.05). The time of occurrence of CVA after carotid endarterectomy affected outcome, and an early CVA (< 4 hours) was associated with a higher mortality at 30 days and at 4 months as a consequence of the initial CVA (p = 0.11). Patients who had a neurologic event more than 4 hours after surgery had a significantly better resolution of their symptoms (66%) compared with patients who had an early neurologic event (35%, p < 0.05). The long-term follow-up of the surviving patients demonstrated an improvement in neurologic function in 75% of the CVA group (36/48) and 92% (76/83) of all patients who had neurologic events in long-term follow-up. PMID- 8518123 TI - Proximal anastomotic failure following infrarenal aortic reconstruction: late development of true aneurysms, pseudoaneurysms, and occlusive disease. AB - Distal anastomotic failure of aortic reconstructions attributable to femoral pseudoaneurysm or outflow stenosis has been well described, but little is known about proximal aortic anastomotic graft failure. A retrospective review was performed between January 1987 and March 1992 to characterize the presentation and management of proximal aortic anastomotic failure. Of 329 consecutive aortic reconstructive operations during this period, 11 (3.3%) were performed to correct complications arising at or adjacent to the proximal anastomosis of an aortic prosthesis. These included anastomotic pseudoaneurysm (n = 6), true aneurysmal dilatation of the residual infrarenal or suprarenal aorta (n = 4), and stenosis of the residual infrarenal aorta (n = 1). The 11 patients had undergone prior infrarenal aortic reconstruction for either aneurysmal (n = 5) or occlusive (n = 6) disease an average of 120 months (range 36 to 175 months) before detection of proximal para-anastomotic graft failure. Eighty-two percent (n = 9) of the proximal lesions were asymptomatic and were discovered incidentally during unrelated medical evaluations. Excluding the six pseudoaneurysms, four of the remaining five lesions developed in a relatively long segment of residual infrarenal aorta, including aneurysm above the graft (n = 2), aneurysm below a proximal end-to-side anastomosis (n = 1), and progressive proximal aortic atherosclerosis (n = 1). Tube graft replacement of the proximal lesions was the most frequently performed operation (n = 7); renal artery reimplantation or bypass was necessary in five cases (45%). Although there was no operative mortality, significant surgical morbidity occurred in three patients (27%). Proximal aortic graft complications tended to be asymptomatic and difficult to repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518124 TI - Superiority of balloon occlusion arteriography to reactive hyperemic arteriography in visualization of distal lower limb vessels. AB - Balloon occlusion arteriography was performed in 38 lower limbs; reactive hyperemic arteriography was also performed in 16 of these limbs. To assess the safety and utility of this technique the balloon occlusion arteriograms of all 38 patients were reviewed retrospectively by a vascular surgeon and vascular radiologist who were unaware of the patient's identity and ultimate treatment. After the arteriograms were reviewed and the outflow vessels identified, a decision was made regarding operability and optimal recipient vessel for distal bypass. Twenty-two of the 38 patients underwent balloon occlusion arteriography only, and 21/22 (95.5%) of these patients only had studies deemed adequate for surgical planning. Twelve of the 16 (75%) patients underwent both reactive hyperemic arteriography and balloon occlusion arteriography; potential distal outflow vessels not seen on reactive hyperemic arteriograms were observed on balloon occlusion arteriograms. In only 4/16 (25%) patients the balloon occlusion arteriograms did not yield additional information. No complications were associated with this technique. Approximately 8.5 g of iodine per run is used for balloon occlusion arteriography compared with approximately 37 g of iodine per run for reactive hyperemic arteriography. Balloon occlusion arteriography is a safe and accurate adjunctive technique that can be used when identification of lower limb vessels is critical. PMID- 8518125 TI - Continuous transcranial Doppler ultrasonography and electroencephalography during carotid endarterectomy: a multimodal monitoring system to detect intraoperative ischemia. AB - Transcranial Doppler ultrasonography (TCD) and EEG monitoring during carotid endarterectomy provide continuous information on the electrical activity of the cerebral cortex, blood flow velocities in the ipsilateral middle cerebral artery, and the occurrence of microemboli. One hundred thirty carotid endarterectomies performed with TCD and EEG monitoring were studied prospectively. During cross clamping of the carotid artery a high correlation was found between EEG asymmetry and reduction of blood flow velocity in the middle cerebral artery (p < 10(-6), Student's t test). Microemboli were detected in 80 patients during the operation. Although not statistically significant, this occurrence of microemboli was associated with signs and symptoms of intraoperative ischemia (p = 0.08, Fisher's exact test). In comparison with earlier studies, a tendency toward intraoperative stroke reduction was noted. Only one nondisabling intraoperative stroke occurred (0.8%). In addition to the EEG, TCD monitoring of hemodynamic changes and microemboli in the middle cerebral artery provides important information to the surgeon instantaneously. TCD monitoring of blood flow velocities and embolism during carotid endarterectomy may help to reduce the number and gravity of intraoperative stroke. PMID- 8518126 TI - Natural history of abdominal aortic aneurysm: a survey of 63 patients treated nonoperatively. AB - During a 10-year period in which 735 patients presented with abdominal aortic aneurysms to our clinic, 63 were not offered operative treatment. The primary reason for choosing conservative treatment was concomitant diseases that increased the risk of operation. After 2 years of followup, half of the patients died, and the cumulative 5-year survival rate was 15%. Aneurysm rupture was the primary cause of death. The cumulative 5-year mortality hazard rate from rupture was 0.36, corresponding to an annual risk of rupture of 7%. The cumulative 5-year hazard rate of death from all other causes was 1.53, corresponding to an annual risk of 30%. Diameter of the aneurysm was found to be the only factor with a significant impact on the rate of rupture. The cumulative 5-year hazard rate of rupture among patients with aneurysms < 6 cm and > or = 6 cm was 0.2 and 0.6, respectively, corresponding to an annual risk of rupture of less than 5% and 10% to 15%, respectively. However, neither diameter nor other risk factors had significant influence on the time of rupture. In our opinion, once the diagnosis is confirmed the patient should be offered aneurysm resection if the general health status permits anesthesia. PMID- 8518127 TI - Prevalence of unsuspected abdominal aortic aneurysms in male veterans. AB - Abdominal aortic aneurysms (AAA) are potentially lethal arterial lesions that are best managed by elective surgical repair. However, asymptomatic AAAs may go undetected on routine physical examination or patients with such lesions may not consult a physician. To determine the prevalence of asymptomatic AAAs in a high risk population, we retrospectively reviewed all abdominal CT scans on veterans > 50 years of age that had been ordered for indications other than aneurysmal disease during a recent 10-month period. Of the 111 patients studied, 15 (13.5%) had suprarenal and/or infrarenal AAAs (one patient had both). Patients with AAAs were significantly older (p = 0.0001) and were heavier tobacco users (p = 0.003). For patients > 60 years of age with peripheral vascular occlusive disease and a history of tobacco use, there was a 29.2% prevalence for AAA compared with 0% in those without any of these risk factors (p = 0.04). There was a very definite trend suggesting that patients with peripheral vascular disease (p = 0.06) were more likely to have an AAA. Because of the high prevalence of AAAs found in this population we then conducted a prospective study over a 24-month period during which patients > 60 years of age with known peripheral vascular disease and a history of smoking who presented to the vascular laboratory for evaluation of problems not related to AAA were asked to undergo an abdominal CT scan. Fifty-six volunteers agreed to participate in the study. Seven patients had AAAs and one patient had an isolated iliac aneurysm, for a 14.3% overall prevalence of aneurysms.2+ d PMID- 8518128 TI - Complications of arteriography in a recent series of 707 cases: factors affecting outcome. AB - Seven hundred and seven consecutive arteriograms were analyzed regarding the effects of various factors on clinical outcome. Complication rates were assessed regarding age, inpatient or outpatient procedures, operator caseload, clinical indication, preoperative renal disease, approach site, graft puncture, selective injection of arteries, amount of contrast, and catheterization time. The major complication rate for arteriography was 7% and the mortality rate was 0.7%. The complication rates for femoral and axillary approaches, respectively, were local, 9% and 27%; nervous system, 1.4% and 11%; and major, 6% and 24% (p = 0.0075, p < 0.0001, and p < 0.0001, respectively). Brachial plexus injury was noted in 13% of the patients undergoing the axillary approach. There was a trend toward a higher overall complication rate in four-vessel arch aortograms with selective vs. nonselective carotid injections, but both had similar neurologic complications. More contrast was used in patients with post-arteriogram renal failure, 224 ml vs. 168 ml. The complication rates were directly related to catheterization time, amount of contrast, and number of vessels punctured. There was a trend toward a higher complication rate in physicians with a lower caseload. In conclusion, arteriography is still associated with significant morbidity and mortality. The transfemoral approach is safer than the transaxillary route, even in patients with femoral graft punctures. PMID- 8518129 TI - Use of CT for diagnosis of traumatic rupture of the thoracic aorta. AB - CT imaging of traumatic aortic rupture has been both advocated and disparaged in the current literature as a reliable diagnostic modality. In a retrospective review of blunt chest trauma patients at our institution evaluated by both thoracic CT and arteriography, we found a 17% false negative rate and a 39% false positive rate. Although we feel CT is not sufficiently sensitive at present to evaluate traumatic rupture of the aorta directly, it is an invaluable adjunctive imaging modality for stable blunt chest trauma patients with equivocal chest radiographs or arteriograms. PMID- 8518130 TI - Duplex Doppler investigation of suspected vascular lesions at the carotid bifurcation. AB - This prospective study was undertaken to evaluate the role of duplex Doppler (DD) scanning in the diagnosis of masses of suspected vascular origin at the carotid bifurcation. We also assessed the different DD signs of carotid body tumors, especially the difference in resistance index (RI) in the external carotid artery on the side of the tumor. Over a 3-year period (1987-1991) all patients (n = 50) with masses of suspected vascular origin at the angle of the mandible underwent DD investigation. The clinical diagnoses included carotid body tumors and carotid bifurcation area aneurysms. Arteriography was also performed in all patients. DD examination diagnosed carotid body tumors in 11 patients, aneurysms in 5, nonvascular lesions in 11, carotid artery kinks in 10, and a prominent carotid bifurcation in 13 patients. In 23 of 50 patients (46%) no pathology (kinks and prominent vessels) was present. DD imaging proved to be 100% accurate in diagnosing these lesions as determined by arteriography. The DD findings in carotid body tumors demonstrated a "wineglass" bifurcation containing a lesion with echoes as well as pronounced and turbulent multidirectional flow ("hypervascular tumor flow"). Low-resistance flow was present in the external carotid artery in 80% of patients, indicating the blood supply of the tumor. Patients with lumps of suspected vascular origin at the carotid bifurcation should be initially investigated by DD examination, which can accurately exclude the diagnosis of carotid body tumors and carotid aneurysms and clearly eliminate arteriography in these patients. PMID- 8518131 TI - Role of arteriography for blunt or penetrating injuries in proximity to major vascular structures: an evolution in management. AB - Over a 14-month period at Boston City Hospital, 93 consecutive patients who had received a blunt or penetrating extremity injury in proximity to a major vascular structure were evaluated. All patients were totally asymptomatic and underwent arteriography for proximity as a sole indication. Twenty-seven patients (27%) were found to have abnormal arteriograms. Muscular branches of the profunda femoris artery were the most frequently injured arteries (28%). Arterial spasm (41%) was the most common radiographic finding. All patients were managed nonoperatively and followed closely by serial pulse examinations. Follow-up arteriography or duplex scanning was used in isolated cases. No patients in this study required operative intervention based on arteriographic findings. No patients have subsequently required operative intervention for delayed arterial abnormalities. Based on these findings we believe the use of arteriography for asymptomatic injuries in proximity to major vascular structures is unwarranted. PMID- 8518132 TI - Ischemia with intermittent reperfusion reduces functional and morphologic damage following renal ischemia in the rat. AB - Attempts to minimize ischemic injury by interrupting a given ischemic period might be compromised if repeated bouts of reperfusion injury occurred. To determine whether intermittent ischemia improved or worsened functional and morphologic outcome of renal ischemia, halothane-anesthetized rats underwent a right nephrectomy and placement of a snare about the left renal vascular pedicle at 37 degrees C. Eleven animals underwent 45 minutes of continuous renal ischemia (C-ISC), whereas 10 animals received 45 minutes of vessel occlusion interrupted (I-ISC) at 15 and 30 minutes by snare release and 5 minutes of reperfusion. A group of three sham rats underwent the above procedure but did not have the snare tightened. Blood samples were drawn preoperatively and 24, 48, and 72 hours postoperatively for creatinine analysis. At 72 hours the animals were sacrificed and their kidneys morphologically evaluated. The C-ISC group had a significantly higher mean postoperative plasma creatinine (p < 0.01) as well as significantly higher plasma creatinine levels at 24 (p < 0.005) and 48 hours (p < 0.05) than did the I-ISC group. The C-ISC group also demonstrated significantly greater histologic damage than the I-ISC group (p < 0.002) when assessed by a pathologist blinded to the intervention. Sham rats did not demonstrate functional or morphologic damage. These data demonstrate a significantly improved outcome when 45 minutes of renal ischemia is interrupted by periods of reperfusion. We are led to conclude that in this setting reperfusion injury did not overwhelm the salutary effects of interrupting the 45-minute ischemic event. PMID- 8518133 TI - The direct effect of graft compliance mismatch per se on development of host arterial intimal hyperplasia at the anastomotic interface. AB - To study the direct and sole effect of compliance mismatch on anastomotic intimal hyperplasia of the host arterial wall and to minimize possible confounding factors, dogs with a low thrombotic potential were selected as experimental subjects. Externally supported 6 cm x 5 mm Dacron grafts with a compliance value of approximately 1/300 of the host artery were implanted into the carotid arteries with end-to-end anastomoses on one side and end-to-side anastomoses on the other. The control graft was an autogenous carotid artery segment 4 cm in length transplanted into the femoral artery. Eight cases (24 grafts) were studied for 1 year and three (nine grafts) for 6 months. All were patent throughout the study period except for two noncompliant grafts with end-to-end anastomoses; thrombosis was the documented cause of occlusion. For the patent grafts, follow up arteriograms showed no progressive narrowing of noncompliant anastomoses. Whether compliant or noncompliant, light microscopy studies showed slight intimal thickening within 1 to 2 mm of the anastomotic line, possibly the result of the normal healing response to stitch and surgical trauma. Quantitatively, 22 measurements representing longitudinal and circumferential thickness of the neointima were taken at each of the 40 patent noncompliant and 22 patent compliant control anastomoses. There was no statistically significant difference in anastomotic neointimal thickness in compliant and noncompliant grafts or for the different implantation periods. These data suggest that graft/host artery compliance mismatch does not cause arterial intimal hyperplasia at the anastomotic interface. PMID- 8518134 TI - Abdominal aortic surgery with concomitant congenital renal fusion. AB - The association between aortic pathology and congenital renal fusion adds little morbidity or mortality to the natural history of either entity. Nevertheless, it complicates the management of aortic pathology, specifically degenerative atherosclerotic disease. The therapeutic goal is to resect the aneurysm or bypass the occlusive segment while preserving renal function. Important principles in the management of these difficult patients include accurate preoperative detection and characterization of the renal abnormality, complete familiarity with the likely anatomic variations associated with this anomaly, adequate exposure of the aortic lesion while preserving renal perfusion, and avoidance of injury to a frequently abnormally located collecting system. In this review we report two cases of abdominal aortic aneurysm associated with congenital renal fusion. The principles of management are thoroughly discussed, and guidelines aimed at facilitating decisions made during the clinical treatment of these difficult patients are suggested. PMID- 8518135 TI - Aortoiliac occlusive vascular disease in association with congenital pelvic kidney. AB - Congenital renal ectopia, although a rare entity, creates potential difficulties in the management of patients requiring aortic surgery. An increasing number of vascular patients with renal transplants who have renal ectopia are being encountered as well. Therefore a management plan is desirable. A recent case of aortoiliac occlusive disease associated with congenital pelvic kidney requiring aortobifemoral bypass grafting is described. A brief review of the anatomy, embryology, and management is given. PMID- 8518136 TI - Vascular surgery-associated ureteral injury: zebras do exist. AB - This report describes a case of direct ureteral injury sustained during retroperitoneal vascular surgery. The diagnosis was delayed and treatment was complicated by infection. To address the patient's problem initially and then to consolidate our impressions, a literature review was undertaken. The conclusions from this review suggest that direct ureteral injury during vascular surgery is rare but most common during redo surgery, is just as likely to be missed as discovered during surgery, and when missed may be so for months. The diagnostic delay is caused by a varied and often misleading presentation, and a ureteral contrast study is the ultimate diagnostic tool. In these delayed cases the typical ureteral treatment is a stented ureteroureterostomy or nephrectomy. In the present case the patient was otherwise healthy; therefore an aggressive attitude to renal salvage was taken. This is a unique case of ileal conduit replacement of the damaged ureter for this specific situation. Five years after repair, renal function is stable without infectious complications. The current literature would suggest that the vascular graft may be left undisturbed if the urine is sterile. If infection is present, graft removal appears the standard of care and was successful in the present case. PMID- 8518137 TI - Omphalocaval shunt: an alternative procedure for portal decompression. AB - We report a case in which umbilical vein was used to construct an omphalocaval shunt in a patient with a long history of alcoholic liver disease and recurrent esophageal and gastric variceal bleeding episodes. The indication for the choice of this procedure included the presence of dense adhesions in the porta hepatis, arteriographic documentation of continuity with the portal venous system, and an umbilical vein 12 mm in internal diameter. The hypertensive portal system was successfully decompressed and proved patent 6 months postoperatively. PMID- 8518138 TI - Familial carotid body tumors: incidence and implications. AB - Carotid body tumors may occur sporadically (90%) or in a familial pattern (10%). One third of the patients with familial disease have bilateral tumors. We report the case of a patient with bilateral carotid body tumors and a strong family history of such tumors. Details of his evaluation and treatment are reviewed. Relatives of patients with carotid body tumors should be examined carefully, and any suspicious neck mass should be appropriately investigated. PMID- 8518139 TI - Acute and chronic upper extremity ischemia. II. Small vessel arterial occlusive disease. PMID- 8518140 TI - Platelet interactions with the vessel wall and prosthetic grafts. AB - Most physicians are aware of the important role that platelets play in thrombus formation. The mechanisms that regulate platelet function are now understood at the molecular level. The same biologic processes that control platelet participation in the hemostatic process also allow platelets to interact with the vessel wall. This review will describe the interaction of platelets with the vessel wall and prosthetic grafts and the physiologic basis and clinical contribution of platelet inhibition to long-term graft patency. PMID- 8518141 TI - Guy de Chauliac (1300-1370): the "father of surgery". PMID- 8518142 TI - Food safety measures for eggs and foods containing eggs. PMID- 8518143 TI - Yellow fever. PMID- 8518144 TI - Expanded programme on immunization. Eradication of poliomyelitis. PMID- 8518145 TI - Beating the narcos. Interview by Michael Gillard. PMID- 8518146 TI - Nursing in Canada: the same but different. PMID- 8518147 TI - Nurses work. Katie completes her quest. PMID- 8518148 TI - Nurses work. Home is where the heart is. PMID- 8518149 TI - Audit of inhaled asthma therapy. AB - The problems patients experience with inhaled asthma therapies are well documented. In an attempt to overcome these, the British Thoracic Society investigated the expansion of the respiratory nurse specialist's role to cover some of the more problematic areas of deficiency. In preparation for this expansion, the authors carried out an audit on 100 adults attending an asthma clinic. It established that more than half of the patients did not use their inhaler devices properly, and indicated which groups and skills required intervention from the respiratory nurse. PMID- 8518150 TI - Explaining solution focused therapy. AB - Psychotherapies have tended to concentrate on clients' complaints in an attempt to overcome their problems: solution focused therapy, on the other hand, looks for their strengths, competencies and potentials, and enables them to recognise and build on them. The authors explain the basis of the therapy, then illustrate how it operates in practice with three short case studies. PMID- 8518151 TI - Outcomes of nursing: a workshop report. PMID- 8518152 TI - A teaching guide for qualified nurses. AB - The teaching of students, colleagues, patients and the public is taking up an increasingly higher proportion of qualified nurses' time. The quality and skills required for this are usually held by these nurses, but they lack confidence in showing them. By adopting a nursing process approach to teaching in clinical areas, the author shows how the skills of clinical nurses are similar to those required in teaching, and offers guidance on how nurses can approach their teaching responsibilities in their own areas of practice. PMID- 8518153 TI - Z and the art of management. PMID- 8518154 TI - Travellers' health: sick-birth caravans. PMID- 8518155 TI - Round the Benner? PMID- 8518156 TI - Information technology. Office sweet. PMID- 8518157 TI - Poor education undermines profession's HIV work. PMID- 8518158 TI - Accident prevention: safe as houses? PMID- 8518159 TI - Rehabilitation: animal magic. PMID- 8518160 TI - Nursing practice: bold or blinkered. PMID- 8518161 TI - Nurses work. Unemployment links with mental illness. PMID- 8518162 TI - Nurses work. Occupational nursing faces redundancy. PMID- 8518163 TI - Primary nursing in contemporary practice. AB - The efficacy of primary nursing as a care delivery system continues to provoke debate. In this wide-ranging discussion, the author identifies the current status of nursing in relation to defined characteristics of its social reality, and shows how primary nursing is 'reconstructing what nurses believe nursing is about'. PMID- 8518164 TI - Promoting urinary continence (continuing education credit). PMID- 8518165 TI - Learning disabilities. Gentle teaching: an introduction. AB - This article aims to raise nurses' awareness of the technique of gentle teaching, which has been used with considerable success in helping people who present challenging behaviours. Based on an appreciation of the essential worth of individuals, and in the need to manage people rather than behaviours, the authors claim that gentle teaching allows nurses to 'see people as they really are'. PMID- 8518166 TI - Learning disabilities. Guy's story. PMID- 8518167 TI - Desperate diaspora. PMID- 8518168 TI - Information technology. Just for the record. PMID- 8518169 TI - Sister Susie. The quality circle merry go round. PMID- 8518170 TI - Funding cuts to AIDS charities are over hasty. PMID- 8518171 TI - The use of monoclonal antibodies in allogeneic bone marrow transplantation. PMID- 8518172 TI - Up-regulation of IL-6-receptors by IL-3 on a plasma cell leukaemia cell line which proliferates dependently on both IL-3 and IL-6. AB - In this report we show that IL-3 up-regulates the expression of IL-6-receptors on a plasma cell leukaemia cell line which proliferates in response to both IL-3 and IL-6. Quantitative binding studies and Scatchard analysis revealed that HSM-2.3 has a single class of high-affinity IL-6 binding sites (200/cell, dissociation constant at the equilibrium 1.43 x 10(-11) M). After stimulation with IL-3, HSM 2.3 has 1200 binding sites. IL-6 receptor mRNA expression was detected in HSM-2.3 only after stimulation with IL-3. PMID- 8518173 TI - Long-term bone marrow culture in Fanconi's anaemia. AB - Fanconi's anaemia (FA) is the most common of the constitutional aplastic anaemias; the mechanisms leading to aplasia in this disease are poorly understood. A number of mechanisms have been implicated in the pathogenesis of acquired aplastic anaemia (AA), including a stem cell defect, an immune reaction against haematopoietic cells or defective function of the marrow microenvironment. To investigate the pathophysiology of this disorder we have performed bone marrow colony forming unit-granulocyte macrophage (CFU-GM) assays and long-term bone marrow culture (LTC) in 22 cases of FA compared with 17 cases of acquired AA. Defective in vitro haematopoiesis was observed in all patients with FA, including several cases with normal peripheral blood counts. The mean CFU-GM value for the FA group was approximately 15 times lower than for the normal group. A correlation was seen between CFU-GM and the severity of neutropenia in FA. In LTC an adherent layer formed in all cases of FA; despite this fact CFU-GM were either not generated or rapidly fell to zero in all patients. LTC is a sensitive method for the detection of impaired granulopoiesis in FA and reveals defects in all patients with this disease. PMID- 8518174 TI - The peanut-agglutinin (PNA)-binding surface components of malignant plasma cells. AB - Plasma cells within bone marrow aspirates from multiple myeloma patients have been shown to be reactive with the lectin peanut agglutinin (PNA). This has been recently exploited by using PNA for purging bone marrow of malignant cells in autotransplantation therapy of the disease. The purpose of this investigation was to isolate and characterize the PNA-binding proteins of myeloma cells. We used the malignant plasma cell-derived line Karpas-620 (K620) as a model, and showed by affinity chromatography, SDS-PAGE, and immunoprecipitation that, among several PNA-binding proteins, a major one is an incompletely sialylated form of CD44. CD44 is a well-known homing receptor protein which is rich in carbohydrate and usually completely sialylated so that it does not react with PNA. We have then examined the PNA reactivity of myeloma cells from different patients and showed a clear difference in the profile of PNA-binding proteins from case to case. Moreover, in contrast to K620 cells, some of the patient plasma cells tested did not have a PNA-binding form of CD44. In conclusion, therefore, we have shown that a number of different proteins participate in PNA binding by malignant plasma cells. Moreover, we have demonstrated a novel, incompletely sialylated form of CD44 on a myeloma cell line. It is known that the level of glycosylation of CD44 and other proteins may affect their function, but how this relates to the malignant behaviour of plasma cells remains to be determined. PMID- 8518175 TI - Possible role of macrophages in the pathogenesis of ethanol-induced bone marrow damage. AB - Adherent-cell-depleted human marrow cells (MC) were cultured on their own or co cultured with monolayers of blood-monocyte-derived macrophages or marrow-derived adherent cells with and without 2 mg ethanol/ml for 24 h. The incorporation of 3H thymidine and 3H-leucine by MC cultured on their own was not significantly influenced by ethanol. By contrast, the incorporation of both radiolabelled compounds was significantly lower in MC from the co-cultures containing ethanol than from those not containing ethanol. This effect was mediated by a diffusible factor produced by macrophages in the ethanol-containing cultures and was independent of intercellular contact. Supernatants from ethanol-containing cultures of marrow-derived adherent cells displayed cytotoxic activity against A9 cells due to the presence of unstable acetaldehyde-albumin complexes. Ethanol inhibited rather than stimulated nitrite production in the MC/marrow-derived adherent cell co-culture system, suggesting that macrophage-derived nitric oxide did not play a role in causing the observed ethanol-related effects. The data indicate that, in the presence of ethanol, macrophages cause inhibition of the incorporation of 3H-thymidine and 3H-leucine into overlying MC, at least partly by oxidizing ethanol to acetaldehyde and releasing some of the potentially cytotoxic acetaldehyde thus formed extracellularly. Bone marrow macrophages may therefore play an important role in the pathogenesis of alcohol-related marrow damage in vivo. PMID- 8518176 TI - Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: motivation for and description of new methods. AB - Kaplan-Meier curves are frequently used to summarize survival, relapse, and chronic graft-versus-host disease (GVHD) data in the bone marrow transplant setting. Some fundamental problems with the use of Kaplan-Meier curves for the summary of relapse and GVHD are described. Alternatively, the use of simple probability and conditional probability curves for summarizing relapse incidence and transplant-related mortality is illustrated with previously published data from a randomized clinical trial. Prevalence curves provide an appropriate alternative for the summary of a transient condition such as chronic GVHD. When combined with Kaplan-Meier curves for survival and/or relapse-free survival, these methods provide a more accurate and comprehensive summary of the various marrow transplant outcomes. These methods of display are also applicable to other settings where more than one type of treatment failure can occur and where follow up time may be variable. PMID- 8518177 TI - Porcine platelets contain an increased quantity of ultra-high molecular weight von Willebrand factor and numerous alpha-granular tubular structures. AB - Immunoelectronmicroscopy of human platelet alpha-granules reveals that von Willebrand factor (vWf:Ag) colocalizes with a small number of discrete tubular structures which appear identical to those observed within the Weibel-Palade bodies of endothelial cells. Although it is likely that tubules are composed of vWf:Ag as they are absent in severe vWD porcine platelets, their exact structural and functional nature is still unclear. In this study quantitative/qualitative analysis of vWf:Ag was undertaken in a series of platelet preparations obtained from normal pigs, normal humans and various vWD patients. Electron microscopy confirmed that normal pig platelet alpha-granules contain numerous, regularly spaced tubular structures eccentrically located and coincident with immunogold staining of vWf:Ag. In contrast, normal human platelet alpha-granules contain significantly fewer tubules (usually four to six) which are absent or reduced in number within various vWD platelet sections. Furthermore, the pig platelet lysates not only contained a full complement of multimers but also demonstrated significant intense staining of ultra-high MW material, irrespective of the presence or absence of proteolytic inhibitors. This ultra-high MW vWf appears similar to that observed within lysates prepared from endothelial cells and is susceptible to degradation to lower MW multimers. This study suggests that the tubular structures within alpha-granules and Weibel-Palade bodies may be composed of, or structurally related to, the ultra-high MW intracellular form of vWf:Ag. PMID- 8518178 TI - Plasma fibrinogen in women: relationships with oral contraception, the menopause and hormone replacement therapy. AB - Plasma fibrinogen was measured in 4837 women aged 25-64 years as part of the Scottish Heart Health Study and Scottish MONICA population surveys. The relationships of oral contraceptive use, the menopause and hormone replacement therapy were examined. Univariate analyses found that women with a history of oral contraceptive use, premenopausal women and those on hormone replacement therapy all had significantly lower fibrinogen levels than women who had never used oral contraceptives, postmenopausal women and non-hormone replacement users respectively. These differences persisted after age standardization. On multivariate analysis, menopausal status and hormone replacement therapy had independent effects on fibrinogen levels. Together with the common risk factors, 9.9% of the total variation in plasma fibrinogen levels was explained. However, less than 1% of this was from the combined menopausal and hormonal factors. These results confirm a postmenopausal rise in fibrinogen level which may be relevant to an increased risk of coronary heart disease. In addition, a protective effect with hormone replacement therapy is noted, although this was probably due to selection bias. PMID- 8518179 TI - Correction of the DNA synthesis defect in vitamin B12 deficiency by tetrahydrofolate: evidence in favour of the methyl-folate trap hypothesis as the cause of megaloblastic anaemia in vitamin B12 deficiency. AB - The critical disturbance of folate metabolism caused by vitamin B12 deficiency which results in megaloblastic anaemia remains controversial. Vitamin B12 is required in the methionine synthase reaction in which homocysteine is converted to methionine and methyl tetrahydrofolate (methyl THF) to THF. The 'methyl-folate trap' hypothesis suggested that failure of demethylation of methyl THF with consequent deficiency of folate co-enzymes derived from THF is the crucial lesion caused by vitamin B12 deficiency. A more recent theory suggested that reduced supply of methionine leads to reduced availability of 'activated formate' and hence of formyl THF and it is this defect that results in failure of folate co enzyme synthesis. The present results, based on deoxyuridine suppression tests on 103 cases of megaloblastic anaemia, show that THF itself is equally capable of correcting the failure of thymidylate synthesis in vitamin B12 deficiency as in folate deficiency. Although not as effective as formyl THF in correcting the dU blocking test in vitamin B12 deficiency, this is equally so for the correction of the test by THF compared with formyl THF in folate deficiency. The results therefore favour the theory that it is in the supply of THF and not of 'active formate' or formyl THF that vitamin B12 plays a critical role in folate metabolism. PMID- 8518180 TI - A role for complement as the major opsonin in the sequestration of erythrocytes from elderly and young donors. AB - Erythrocytes from elderly donors (> 70 years), but not young donors (18-35 years), are shown to undergo sequestration in an in vitro erythrophagocytosis assay. Comparable levels of sequestration are observed for high density erythrocytes from young individuals and both low density and high density erythrocytes from elderly individuals. These cells, which are susceptible to phagocytosis with no additional treatment are collectively termed 'in situ aged' erythrocytes. We present evidence for the involvement of complement in the sequestration of 'in situ aged' erythrocytes and correlate levels of complement bound to 'in situ aged' erythrocytes from young and elderly donors with levels of phagocytosis. We also demonstrate that the in vitro sequestration of erythrocytes from elderly donors can be inhibited by beta-galactosyl sugars and arginine glycine-aspartic acid (RGD) but not by mannose nor by Protein-G, a specific inhibitor of Fc-gamma mediated phagocytosis. These experiments show that IgG is not the major opsonin in the sequestration of red cells from elderly donors. In support of the role of complement rather than IgG as the major opsonin in red cell sequestration, we further demonstrate that C'3 bearing immune complexes block in vitro sequestration of erythrocytes from elderly donors. This competition is not dependent upon the isotype of the immunoglobulin (IgM or IgG) in the complex but rather on the presence of active complement. PMID- 8518181 TI - Expression of human recombination activating genes (RAG-1 and RAG-2) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T-type. AB - In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy (AILD) and in anaplastic large cell lymphoma of T-type (T-ALC), recombinase activating gene (RAG-1 and RAG 2) expression was assessed in six AILD and five T-ALC cases using a sensitive reverse transcriptase (RT) and competitive (C) polymerase chain reaction (PCR). RAG transcripts were not detectable in nine cases with high proliferating activity, suggesting that in most cases the proliferating cells are derived from mature (rearranged) lymphocytes. However, low levels of RAG transcripts were detected in one AILD and one T-ALC case and are consistent with either an involvement of immature lymphoid precursors in the proliferating pool or a deregulated T-cell maturation pathway with persistence of RAG expression. An association between RAG gene expression and poor response to therapy is possible but has to be tested in larger prospective series. PMID- 8518182 TI - Unreliability in immunoassays of erythropoietin: anomalous estimates with an assay kit. AB - We report the finding of inappropriately high estimates of erythropoietin (Epo) in 11% of serum samples tested by one commercial assay kit. These estimates were not confirmed when the same samples were tested independently in four other systems for the immunoassay of Epo. As yet no explanation has been found to account for the anomalously high estimates. PMID- 8518183 TI - A unique case of t(15;17) acute promyelocytic leukaemia (M3) developing into acute myeloblastic leukaemia (M1) with t(7;21) at relapse. AB - This report describes a case of t(15;17) acute promyelcytic leukaemia (APL, FAB subtype M3) with dysgranulopoiesis at diagnosis in a patient who developed myelodysplasia (MDS) and then a second phenotype of t(7;21) acute myeloblastic leukaemia (AML, FAB subtype M1) at the time of relapse. To our knowledge, there is no report of a second phenotype of AML occurring after complete remission (CR) of APL. Furthermore, this is the first report of chromosomal abnormality t(7;21) in a case of AML. Several hypotheses for this unusual course of APL are discussed. PMID- 8518184 TI - The beta + IVS, I-NT no. 6 (T --> C) thalassaemia in heterozygotes with an associated Hb Valletta or Hb S heterozygosity in homozygotes from Malta. AB - In vitro DNA amplification and dot blot analysis with synthetic allele specific oligonucleotides (ASO) identified the beta + IVS, I-6 (T --> C) thalassaemia in 78% of 32 chromosomes from 16 beta-thalassaemia homozygotes in Malta. The preponderance of a single thalassaemia mutation in one population is unusual. The beta + IVS, I-6C thalassaemia mutation was also found in three carriers who had an associated beta globin heterozygosity, i.e. Hb Valletta (or alpha 2 beta 2 87PRO) or Hb S (or alpha 2 beta 2 6VAL). The proportion of Hb A in these cases (av. = 29.7%) provided objective documentation of the relatively mild effect of this mutation on in vivo globin gene expression. However, the expression of homozygous disease was more severe in developing children compared to adults. The beta + IVS, I-6C mutation complicates population testing because heterozygotes can have Hb A2 levels below those classically associated with beta thalassaemia. PMID- 8518186 TI - Extensive meningeal involvement as the primary manifestation of a systemic small lymphocytic lymphoma: favourable outcome after neuraxial irradiation without chemotherapy. PMID- 8518185 TI - Severe anaphylactic transfusion reaction associated with HLA-incompatible platelets. PMID- 8518187 TI - Ticlopidine and aplastic anaemia. PMID- 8518188 TI - Parvovirus B19 and transient erythroblastopenia of childhood. PMID- 8518189 TI - Platelet transfusion refractoriness associated with plasma proteins. PMID- 8518190 TI - A regulatory function for K10 in the establishment of dorsoventral polarity in the Drosophila egg and embryo. AB - Several lines of evidence suggest that the origin of pattern formation of Drosophila embryos must be traced back to oogenesis, to the polarity of the egg chamber. A few early-acting genes, K10, top, grk and cni, have been identified which are assumed to function in a signal transduction process between the germline oocyte and the somatic follicle cells, during which the egg chamber acquires a dorsoventral polarity. K10 has been cloned and was shown to encode a putative transcription factor specifically acting in the oocyte nucleus. In order to characterize further the function of K10, we have analyzed its genetic interactions with grk, top and cni. We show that grk behaves as a dominant partial suppressor of K10. Analysis of the rescuing process of the K10 phenotype by grk shows that: (1) K10 is not indispensable for the establishment of dorsoventral polarity of the egg chamber, since its lack of function can be compensated for by reducing the grk wild-type copy number; (2) grk function is highly dose-sensitive; (3) the rescue process shows an anteroposterior effect suggesting that K10 may also interact with genes involved in anteroposterior pattern formation. These results are compatible with a model in which grk is a dorsalizing signal emanating from the oocyte nucleus, whose level of expression is regulated negatively by the K10 product. PMID- 8518192 TI - Regulation of expression domains and effects of ectopic expression reveal gap gene-like properties of the linked pdm genes of Drosophila. AB - The closely linked POU domain genes pdm-1 and pdm-2 are first expressed early during cellularization in the presumptive abdomen in a broad domain that soon resolves into two stripes. This expression pattern is regulated by the same mechanisms that define gap gene expression domains. The borders of pdm-1 expression are set by the terminal system genes torso and tailless, and the gradient morphogen encoded by hunchback. The resolution into two stripes is controlled by the gap gene knirps. Ectopic expression of pdm-1 at the cellular blastoderm stage leads to disruptions in pair rule gene expression and in anterior segmentation. The broad abdominal domain of pdm-1 protein is lacking in nanos- mutant embryos, and ectopic pdm-1 expression in nanos- embryos leads to a partial restoration of abdominal segmentation. These data suggest that the pdm genes may act in segmentation near the level of the zygotic gap genes. PMID- 8518191 TI - Single-minded regulation of genes in the embryonic midline of the Drosophila central nervous system. AB - Proper development of the midline cells within the Drosophila central nervous system is controlled by the single-minded (sim) gene. The sim protein defines a new subclass of bHLH transcription factors and as such, is predicted to function as a transcriptional regulator of other genes important for midline development. Here we identify two potential targets of sim regulation: the sim gene itself, and the 47F gene, which is expressed specifically in the sim-expressing midline cells. Using a transgene containing sim regulatory sequences fused to beta galactosidase, we show that the sim gene uses two distinct promoters with overlapping temporal specificities, and that expression from the late promoter is autoregulated by sim itself. By expressing sim protein in salivary gland nuclei using the heat-shock inducible Hsp70 gene promoter, we show that sim protein associates with the sim late promoter on polytene chromosomes. In addition, sim protein binds to a small number of additional chromosomal sites, among which are the sites of the 47F gene, and two other genes, Tl and cdi, whose expression also depend on sim function. PMID- 8518193 TI - The c-ets-1 proto-oncogenes in Xenopus laevis: expression during oogenesis and embryogenesis. AB - We previously reported the cloning and sequencing of two cDNAs derived from the Xenopus laevis ets-1 gene (Stiegler et al., 1990). The Xl-ets-1a cDNA encodes a polypeptide highly homologous to known ets-1 proteins. The 3'-UTR contains two AATAAA polyadenylation signals together with three copies of the TTTTTAT sequence thought to confer a maturation-specific polyadenylation and implicated in the deadenylation of dormant mRNAs. Several transcripts with maternal characteristics were detected in oogenesis and early embryogenesis. A marked augmentation of the major transcript in the poly(A)+ fraction was detected at fertilization. Ets-1 transcripts were observed at constant levels during the cleavage stages but decreased abruptly at gastrulation, to reappear from neurulation to late embryogenesis. The possible contribution of 3'-UTR sequence elements to this behavior is discussed. PMID- 8518194 TI - Spemann's organizer: models and molecules. PMID- 8518195 TI - Embryonic induction. AB - The current understanding of the mechanism of embryonic induction is reviewed. The embryological data which are necessary to establish the existence of an inductive process are described and the criteria for the identification of inducing factors are discussed. These criteria comprise: a demonstration that the factor has the appropriate biological activity, that it is expressed in biologically available form at the correct time and place in the embryo, and that when it is inhibited in vivo, the interaction should fail. Current understanding of the molecular basis of competence and threshold responses is discussed. Four case studies are examined in further detail: the dorsoventral patterning in Drosophila is controlled by a gradient of the decapentaplegic gene product, a member of the TGF beta superfamily. Mesoderm induction in Xenopus embryos is thought to be controlled by several factors acting in concert: activins, fibroblast growth factors (FGFs), Wnt proteins and bone morphogenetic proteins (BMPs). The formation of the kidney in higher vertebrates involves a permissive interaction and some molecules are known to be necessary for the process but the identity of the primary inducing signal remains elusive. The anteroposterior pattern in the chick limb is controlled by a morphogen gradient emitted by the zone of polarising activity (ZPA). Although closely mimicked by retinoic acid (RA), this substance is probably not itself the morphogen. In general, the technical advances of recent years have enabled dramatic progress to be made in understanding the molecular basis of embryonic induction. Although much remains to be done, the methods of investigation are now well established. PMID- 8518196 TI - Application of DNA filter hybridization and PCR to distinguish between human and non-human tissues of poor quality. AB - The present report describes a novel approach for the identification of human or non-human specimens after long-term storage in a badly preserved state. The application of the PCR-technique (polymerase chain reaction) using human-specific primers as well as Southern blot (filter) hybridization of the sample DNA to a primate-specific DNA probe enabled us to extend the positive identification beyond the limits of conventional methods such as serological or morphological examinations. PMID- 8518197 TI - Forensic validation of the STR systems SE 33 and TC 11. AB - Population studies on Caucasians from northwest Germany were carried out using the short tandem repeat (STR) systems SE 33 (Locus: ACTBP2) and TC 11 (Locus: 11p15.5). After electrophoresis in PAG 26 alleles could be identified for SE 33 in a sample size of 180 unrelated individuals and 6 alleles were found for TC 11 in 110 individuals. The combined mean exclusion chance for both systems was 0.96 and the discrimination index 0.999. No significant deviations from Hardy-Weinberg equilibrium could be demonstrated. In a small sample of families (SE 33 - n = 21; TC 11 - n = 30) no new mutations could be found. Positive and reproducible results for both STRs could be obtained from 50 pg template DNA. PMID- 8518198 TI - Analysis of the immunohistochemical localization of collagen type III and V for the time-estimation of human skin wounds. AB - Collagen type III and V were visualized immunohistochemically in 79 surgically treated human skin wounds with a wound age between 8 h and 2.5 months. Network like structures positively staining for collagen type III and associated with fibroblastic cells in the wound area were first detectable in a 2.5-day-old skin lesion and occurred regularly in wounds more than 5 days old. Collagen type V appeared first in the wound area after about 3 days, slightly later than collagen type III, and was detectable regularly in wounds with a survival time of 6 days or more. The immunohistochemical detection of collagen type III or type V thus indicates a wound age of at least 2-3 days. The lack of a positive reaction in a sufficient number of specimens indicates a wound age of less than 6 days. Even though both collagen types could also be detected in older wounds (wound age 2.5 months), further information for the time-estimation of older skin wounds cannot be given due to the observation that the time period during which reparative processes can be observed depends on the extent of the wound area. PMID- 8518199 TI - The potential role of bacterial toxins in sudden infant death syndrome (SIDS). AB - Toxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence that Clostridia spp. are associated with SIDS in Britain, strains of Staphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy The pyrogenic toxins, produced by some strains of group A Streptococcus pyogenes as well as staphylococci, are powerful "superantigens" that have significant physiological effects including induction of fever > 38 degrees C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infant's expression of Lewis(a) antigen which acts as a receptor for some microorganisms; viral infections; the effect of mother's smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths. PMID- 8518201 TI - Suspected maternal infanticide in a case of hydranencephaly. AB - A medico-legal autopsy case of hydranencephaly in a male infant which was first suspected of maternal infanticide is reported. The infant was 48 cm in height, weighed 2.86 kg and the circumference of the head, the chest and the abdomen was 32.2 cm, 31.0 cm and 30.4 cm, respectively, with no deformities of the head or body. Autopsy examination, however, revealed a severe defect in the central nervous system. The cranial cavity was filled with a cloudy dark red fluid (ca. 310 ml) instead of the cerebral hemispheres. The residual central nervous tissues were mostly subtentorial structures from the midbrain to the spinal cord namely, corpus mamillare, corpora quadrigemina, corpus pineale, crus cerebri, pons, cerebellum, medulla oblongata and spinal cord. The basal ganglia, thalamus, hypothalamus and chiasma opticum could not be found, although atrophic hypophysis, eyeballs and optic nerves were present. The usual distribution of cerebral blood vessels, especially the branches of the anterior and middle cerebral arteries and Willis' ring, was absent despite the presence of the internal and external carotid arteries. Other organs were, in general, congestive. The marked cortical atrophy of the adrenal glands (left 0.5 g, right 0.6 g), especially the zona fasciculata, was characteristic. The hydrostatic lung test gave partially positive results, but this was considered to be due to artificial respiration by an ambulance man because amniotic fluid components were microscopically noted and fully expanded alveoli were not found. In conclusion, the cause of the infant's death was diagnosed as stillbirth due to aspiration of amniotic fluid caused by the severe defect of vegetative hypothalamic function through hydranencephaly. PMID- 8518200 TI - Neuropathological studies in the brains of AIDS patients with opportunistic diseases. AB - The brains of 70 fatal cases with AIDS were studied by means of immunohistochemistry and in-situ hybridization in a consecutive autopsy series (1985-July 1992). In addition, the neuropathological changes were correlated with the neurological and neuroimaging findings. Opportunistic infections included toxoplasmosis (15 cases), cytomegalovirus (CMV)-encephalitis (6), progressive multifocal leucoencephalopathy (2) and fungal infections (3). Malignant lymphomas were found in 7 patients; 6 involved primarily the CNS, one was metastatic. In 14 cases the neuropathological changes were consistent with HIV encephalitis and HIV leucoencephalopathy. Non-specific lesions occurred in 31 cases. The clinical diagnosis in patients with opportunistic diseases (n = 27) diverged in 15 cases (55%) from the underlying pathology. Toxoplasma gondii, CMV and JC viruses were identified by immunohistochemistry and in-situ hybridization on serial paraffin sections. In addition, antibodies against lymphocyte subsets, tissue macrophages, the glial fibrillary acid protein (GFAP) and myelin basic protein were used to characterize the phenotype of cells and to highlight the degree of gliosis and demyelination. Our results show that the distribution and degree of morphological changes might be helpful for the differential diagnosis antemortem. Since neurological complications may represent the first or sole manifestation of AIDS and risk factors for AIDS are often not known, it should be taken into account that CNS manifestations of AIDS may contribute to a sudden and unexpected death or accident. Opportunistic diseases should be considered as a possible differential diagnosis in cases mimicking the clinical picture of apoplexia or dementia. Furthermore, CNS lesions may be detected postmortem in patients who were not known to suffer from Neuro-Aids during life, indicating that CNS involvement is more widespread than assumed. PMID- 8518202 TI - Improved separation of PCR amplified VNTR alleles by a vertical polyacrylamide gel electrophoresis. AB - The effect of a stacking gel, the pH and crosslinking agent concentration on the resolution and sharpness of PCR amplified VNTR alleles in a vertical discontinuous polyacrylamide gel electrophoresis system was investigated. The experiments show that the use of a low crosslinking agent concentration, a stacking gel and a wide pH difference between the gel buffer and the electrophoresis buffer at the beginning of the electrophoresis resulted in reduced band width and increasing resolution in silver-stained polyacrylamide gels. The importance of sharp DNA fragments is especially emphasized when analyzing multi-allelic DNA loci, that exhibit alleles differing from only few bp to few dozen bp in length, such as variable number of tandem repeat (VNTR) or short tandem repeat (STR) loci. PMID- 8518204 TI - Cigarette smoking during pregnancy lowers aromatase cytochrome P-450 in the human placenta. AB - To clarify whether cigarette smoking during pregnancy causes an organic alteration in placental estrogen producing ability, we determined the catalytic activity of aromatase by the tritiated water assay, and tissue level of aromatase cytochrome P-450 (P-450arom) by the specific enzyme-linked immunosorbent assay, in placental samples from nonsmokers and smokers. As pregnancy progressed, both aromatase activity and P-450arom concentration increased in placentas from nonsmokers and smokers. However, the gradient of the increase was significantly less in heavy smokers (> or = 20 cigarettes a day) than in normal and moderate smokers (< 20 cigarettes a day). At term, the mean aromatase activity and P 450arom concentration in placentas from heavy smokers were significantly lower than in nonsmokers and moderate smokers, while aromatase activity per P-450arom (turnover rate) and the mean placental weight were comparable among the three groups. In contrast, the ratio of aryl hydrocarbon hydroxylase activity to aromatase activity was higher in placentas from heavy smokers. Immunohistochemical studies showed that P-450arom was localized in the cytoplasm of syncytiotrophoblasts of chorionic villi in placentas from both nonsmokers and smokers. These results suggest that the induction of placental P-450arom during gestation is suppressed by maternal smoking, resulting in a reduction in estrogen producing ability, while placental xenobiotic P-450 is induced. PMID- 8518203 TI - Kinetic evidence for a unique testosterone-receptor complex in 5 alpha-reductase sufficient genital skin fibroblasts and the effects of 5 alpha-reductase deficiency on its formation. AB - When 5 alpha-reductase-sufficient genital skin fibroblast (GSF) monolayers are incubated with testosterone (T), they first form androgen (A)-receptor (R) complexes that dissociate at a fast rate [k(37 degrees C = 0.024 min-1]. As T is converted to 5 alpha-dihydrotestosterone (DHT), this population of T-R complexes is eventually replaced by one that dissociates much more slowly [k(37 degrees C) = 0.006 min-1], at a rate typical of DHT-R complexes. During the course of T to DHT conversion, one may observe a population of A-R complexes that has a linear (monophasic) intermediate dissociation rate constant [k(37 degrees C) = 0.012 min 1]; this population cannot simply reflect a mixture of T- and DHT-R complexes. The rate at which the complexes are processed from one dissociative form to the next varies with the incubation temperature and the presence or absence of serum in the medium; it also varies within and among GSF strains under apparently constant conditions. To explain these facts, we propose a model that enables the 5 alpha-reductase enzyme to influence the processive dissociative behaviour of T R complexes by engaging in some sort of coupling with the AR. The proposal is strengthened by a set of observations in cells with constitutive, mendelian or inhibitor-induced 5 alpha-reductase deficiency that preclude a simple quantitative relation between A-R complex processing and the extent of T to DHT conversion. PMID- 8518205 TI - Maturational changes in steroidogenesis in the inner and outer zones of the guinea pig adrenal cortex. AB - Studies were done to determine the effects of age on steroidogenesis in the inner (zona reticularis) and outer (zona fasciculata plus glomerulosa) zones of the guinea pig adrenal cortex. In 35-day-old animals, cortisol production by adrenal outer zone cells was approximately twice as great as that by inner zone cells. With aging, cortisol secretion by inner zone cells decreased to very low levels, but there was no detectable change in the capacity for cortisol production by the outer zone. However, the outer zone comprised a progressively decreasing fraction of the total adrenal mass in older animals. To determine the basis for the decline in cortisol production by inner zone cells with aging, the activities of several steroidogenic enzymes were determined. Microsomal 21-hydroxylase activity was greater in the inner than outer zone but was not significantly affected by age. By contrast, 17 alpha-hydroxylase activity was greater in the outer zone at all ages, and decreased with aging in the inner but not the outer zone. Mitochondrial cholesterol sidechain cleavage and 11 beta-hydroxylase activities were also higher in the outer than inner zone and declined in the inner zone only in older animals. The decrease in inner zone cholesterol sidechain cleavage activity with aging was proportionately greater than the age-dependent changes in other enzyme activities. The results indicate that the effects of aging on steroidogenesis are both zone- and enzyme-specific. The overall decline in cortisol secretion by the guinea pig adrenal cortex with aging is attributable to both a decrease in cortisol production by the cells of the zone reticularis and a disproportionate increase in the mass of the gland comprised by this zone. The decrease in cortisol secretion correlates closely with a decline in cholesterol sidechain cleavage activity in the zona reticularis, and may be causally related. PMID- 8518206 TI - Antioxidant properties of steroids. AB - To determine the relative ranking of antioxidative potential of various steroids the effect of 14 steroid compounds on the fluorescence of phycoerythrin was monitored over time following the addition of a peroxy radical generator 2,2'-azo bis (2-amidino-propane) dihydrochloride. The rate of decay of fluorescence in the presence of a 200 nM of 17 beta-estradiol, 17 alpha-estradiol and estriol expressed as percentages of the rate of decay in the absence of these compounds (control curve), were 74.1 +/- 6.3, 84.0 +/- 5.42 and 64.2 +/- 2.53%, respectively (P < 0.005). Cortisone and corticosterone appeared to have very mild pro-oxidant properties. Other steroids tested such as estrone, testosterone, progesterone, androstenedione, dehydroepiandrosterone, cortisol, tetrahydrocortisone, deoxycorticosterone and aldosterone had no significant antioxidant properties. It is concluded that estrogens especially estriol and 17 beta-estradiol are naturally occurring antioxidants. PMID- 8518207 TI - 3 beta-hydroxysteroid dehydrogenase activity in tissues of the human fetus determined with 5 alpha-androstane-3 beta,17 beta-diol and dehydroepiandrosterone as substrates. AB - 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD)/delta 5-->4-isomerase activity in steroidogenic tissues is required for the synthesis of biologically active steroids. Previously, by use of dehydroepiandrosterone (3 beta-hydroxy-5 androsten-17-one, DHEA) as substrate, it was established that in addition to steroidogenic tissues 3 beta-HSD/delta 5-->4-isomerase activity also is expressed in extraglandular tissues of the human fetus. In the present study, we attempted to determine whether the C-5,C-6-double bond of DHEA serves to influence 3 beta HSD activity. For this purpose, we compared the efficiencies of a 3 beta-hydroxy 5-ene steroid (DHEA) and a 3 beta-hydroxy-5 alpha-reduced steroid (5 alpha androstane-3 beta,17 beta-diol, 5 alpha-A-diol) as substrates for the enzyme. The apparent Michaelis constant (Km) for 5 alpha-A-diol in midtrimester placenta, fetal liver, and fetal skin tissues was at least one order of magnitude higher than that for DHEA, viz the apparent Km of placental 3 beta-HSD for 5 alpha-A diol was in the range of 18 to 40 mumol/l (n = 3) vs 0.45 to 4 mumol/l for DHEA (n = 3); for the liver enzyme, 17 mumol/l for 5 alpha-A-diol and 0.60 mumol/l for DHEA, and for the skin enzyme 14 and 0.18 mumol/l, respectively. Moreover, in 13 human fetal tissues evaluated the maximal velocities obtained with 5 alpha-A-diol as substrate were higher than those obtained with DHEA. A similar finding in regard to Kms and rates of product formation was obtained by use of purified placental 3 beta-HSD with DHEA, pregnenolone, and 3 beta-hydroxy-5 alpha androstan-17-one (epiandrosterone) as substrates: the Km of 3 beta-HSD for DHEA was 2.8 mumol/l, for pregnenolone 1.9 mumol/l, and for epiandrosterone 25 mumol/l. The specific activity of the purified enzyme with pregnenolone as substrate was 27 nmol/mg protein.min and, with epiandrosterone, 127 nmol/mg protein.min. With placental homogenate as the source of 3 beta-HSD, DHEA at a constant level of 5 mumol/l behaved as a competitive inhibitor when the radiolabeled substrate, [3H]5 alpha-A-diol, was present in concentrations of 20 to 60 mumol/l, but at lower substrate concentrations the inhibition was of the mixed type; similar results were obtained with [3H]DHEA as the substrate at variable concentrations in the presence of a fixed concentration of 5 alpha-A diol (40 mumol/l).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8518208 TI - Expression of 5 alpha-reductase in bacteria as a trp E fusion protein and its use in the production of antibodies for immunocytochemical localization of 5 alpha reductase. AB - A cDNA encoding a full-length rat 5 alpha-reductase was isolated using female rat liver mRNA and the polymerase chain reaction, and fused to the Escherichia coli trp E gene in a pATH expression vector. The trp E-5 alpha-reductase fusion protein expressed in bacteria and a synthetic oligopeptide corresponding to the C terminus of rat 5 alpha-reductase were used as antigens to produce rabbit polyclonal antibodies to 5 alpha-reductase. Antibodies to the 5 alpha-reductase portion of the fusion protein and to the peptide were purified by affinity chromatography. Antibodies against the 5 alpha-reductase fusion protein reacted with a single component of rat liver microsomes with M(r) 26,000 on Western blots, consistent with the size of 5 alpha-reductase predicted from its cDNA, and with a M(r) 23,000 component on Western blots of detergent extracts of rat ventral prostate nuclei; other rat ventral prostate cellular fractions (mitochondrial, microsomal, cytosol) bound little or no antibody. Antibody against the synthetic peptide reacted with a M(r) 26,000 component of rat liver microsomes as well as with several components in various cellular fractions of rat ventral prostate. With anti-5 alpha-reductase fusion protein antibodies, specific immunocytochemical staining was observed in the epithelial cell nuclei of the rat ventral prostate, seminal vesicle, epididymis and other accessory sex glands. This nuclear staining was specific, since antibodies from non-immunized rabbits did not give nuclear staining and preincubation of the anti-5 alpha reductase fusion protein antibodies with the trp E-5 alpha-reductase fusion protein eliminated nuclear staining. Incubation of antibodies with trp E (without the 5 alpha-reductase fusion) had no effect on nuclear staining. Specific staining was not detected in the cytoplasm of these epithelial cells. Little or no specific staining was observed in stromal cells in these rat tissues. Human prostate was also immunocytochemically stained with this antibody. Specific staining was found in both epithelial and stromal cell nuclei. PMID- 8518209 TI - The metabolic fate of [3H]estradiol in relation to dietary intake of boron in ovariectomized rats. AB - It has been reported that boron (B) deprivation reversibly lowers plasma estradiol levels in postmenopausal women. In order to establish whether this reflects disturbances in the estrogen catabolic pathway and in particular in catechol estrogen metabolism, the influence of dietary B on the catabolism of [3H]estradiol-17 beta has been studied in ovariectomized rats. Rats were given diets containing < 0.1 or 40 mg B.kg-1, ovariectomized and then infused with [3H]estradiol-17 beta using osmotic pumps. Analysis of urine samples for conjugated, catechol and non-catechol estrogens did not reveal any effects of B on the recovery or the metabolic fate of tritium from the infused estradiol. These results do not therefore support the proposal that B influences estrogen catabolism by interacting with catechol estrogens. PMID- 8518210 TI - In vivo stimulation of aldosterone biosynthesis by endothelin: loci of action and effects of doses and infusion rate. AB - Infusion of endothelin-1 (ET-1) into rats increased adrenal mitochondrial synthesis of aldosterone from deoxycorticosterone and the adrenal cytosolic content of aldosterone. The dose-response relationships for these last two effects of ET-1 were found to be biphasic with a maximum (corresponding to 80 to 200% increase) at 50 to 80 ng ET-1/kg/min, and were also dependent on the infusion rate. Plasma aldosterone levels were also increased in a similar ratio. Previous infusion of the converting enzyme inhibitor enalapril did not affect the ET-1-induced increase in steroidogenesis. Finally, pregnenolene production was also increased in incubations of mitochondria from treated rats. These results indicate that ET-1 augments aldosteronogenesis by increasing the early as well as the late pathway. These effects were independent of the formation of angiotensin II. Isolated glomerulosa cells responded to ET-1 increasing aldosterone production in a dose-related fashion. These results confirm a direct effect of ET 1 on the adrenal gland in vivo. PMID- 8518212 TI - New synthesis of 2 beta-hydroxy-19-oxoandrost-4-ene-3,17-dione and its 2 beta-18O analog. AB - Treatment of 19-[oxygenated]-androst-4-ene-3,17-dione with Mn(AcO)3 and ClCH2COOH in benzene gave epimeric mixtures of the corresponding 2 zeta-chloroacetates and 2 zeta-acetates. The products were processed to give the title compound. For the synthesis of the 2-18O analog, ClCH2C18OOH was used, which was prepared from ClCH2COCl. PMID- 8518211 TI - Studies on the 14 alpha-hydroxylation of progesterone in Mucor piriformis. AB - Cell-free extracts with high 14 alpha-hydroxylase activity were prepared from induced vegetative cell cultures of Mucor piriformis by grinding in potassium phosphate buffer (0.05 M, pH 8.0) containing glucose (0.25 M), KCl (1 mM), glutathione (1.0 mM) and glycerol (10%). Although the ideal pH for preparing the cell-free extract from vegetative cells was 8.0, the pH optimum of the hydroxylase was found to be 7.6. Microsomes (2.0 mg) prepared from the crude cell free extract hydroxylated progesterone to 14 alpha-hydroxyprogesterone in approximately 60% yields in 30 min in the presence of NADPH and O2. Microsomes prepared from the uninduced cells did not contain any 14 alpha-hydroxylase activity. The hydroxylase activity was inhibited to a significant extent by CO and p-chloromercuribenzoate whereas moderate inhibition was noticed in the presence of SKF-525A, metyrapone and N-methylmaleimide indicating the possible involvement of the cytochrome P-450 system in the reaction. The membrane bound hydroxylase was solubilized using Triton X-100 and the solubilized fraction contained nearly 35% of the original hydroxylase activity. PMID- 8518214 TI - Brain cancer scare hits U.S. phone manufacturers. PMID- 8518213 TI - Kinetic evidence for the involvement of a common enzyme in the microsomal reduction of retinal and androstenedione in rat liver. AB - Androst-4-ene-3,17-dione (androstenedione) was found to be a potent competitive inhibitor of the NADH-supported reduction of retinal in rat hepatic microsomes (Ki 42 microM, Km/Ki ratio 1.1). Similarly, the NADH-mediated reduction of androstenedione was inhibited in mixed fashion by retinal (Ki 12 microM, Km/Ki ratio 0.34). In subsequent experiments the cofactor NADH exhibited an identical Km (8 microM) in the microsomal reductions of both substrates. Acidic pH markedly stimulated the microsomal reduction of androstenedione to testosterone and was also found to enhance retinal reduction to retinol, although the latter reaction exhibited a distinct pH optimum between 6.0 and 6.5. These results suggest that a common enzyme may participate in the reduction of both substrates but at least one other enzyme probably participates in hepatic microsomal testosterone production. PMID- 8518215 TI - Debate over passive smoking hotter than ever. PMID- 8518216 TI - Ovarian cancer: any progress? PMID- 8518217 TI - Improving cancer care world wide. PMID- 8518218 TI - Epidemiologic pathology of ovarian cancer from the Vaud Cancer Registry, Switzerland. AB - OBJECTIVE: To provide further information on the descriptive epidemiology and survival of ovarian cancer patients by specific histologic types. STUDY DESIGN: Descriptive epidemiological study. Cases of ovarian cancer registered between 1974 and 1988 in the Vaud Cancer Registry, Switzerland (based on a population of approximately 530,000 inhabitants), were analysed. RESULTS: A total of 649 cases were registered, corresponding to an overall age-standardized (world population) incidence of 9.6/100,000. The most common histotype was serous carcinoma (41%, incidence rate 4.0/100,000), followed by endometrioid (13%), mucinous (12%), clear cell (5%), and undifferentiated carcinomas (3%); 20% of the cases were classified as 'epithelial, unspecified', and 6% were non-epithelial cancers. There was a tendency for the incidence of all epithelial types to rise up to the seventh decade of age, and to level off thereafter. The increases between the ages of 45 and 65 were, however, mostly in serous carcinomas whose proportion of total ovarian epithelial cancer peaked in middle age. Overall, 5-year relative survival was 32%. Survival rate was 32% for serous carcinomas, but was significantly higher for endometrioid (51%) and, among nonepithelial neoplasms, for germ-cell cancers (68%). Survival rates were poor for undifferentiated and 'epithelial, unspecified' carcinomas (16%). Relative survival was systematically higher below age 60 than at age 60 or over. In the two subsequent calendar periods examined (divided according to the approximate time when the use of platinum-based chemotherapy began to spread, i.e., 1982), 5-year relative survival rates were 28% and 36%, respectively (chi 1(2) = 6.1, p = 0.02). CONCLUSION: The present report is a population-based description of the epidemiologic pathology and prognosis of ovarian cancer, and provides evidence of a significant improvement of survival over the past decade. This may be due to changed diagnostic methods (e.g., ultrasonography), improved surgical approach, (platinum-based) chemotherapy, or a combination of all these factors. PMID- 8518219 TI - Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5 fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients. AB - BACKGROUND: The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling. PATIENTS AND METHODS: Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (T1-3, N1) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA- arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d x 28 days, followed by 500 mg i.m. twice weekly during 5 months. RESULTS: The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA- group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p = 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA- group (p = 0.12). Patients > or = 60 years benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p = 0.18), but within subgroups analysed there was an advantage for MPA+ in patients > or = 55 years (p = 0.002) and in pT1 patients (p = 0.045). CONCLUSIONS: High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients. PMID- 8518220 TI - Randomized phase II trial of iproplatin and carboplatin in advanced breast cancer. The EORTC Early Clinical Trials Group and the EORTC Data Center. AB - BACKGROUND: The observed activity of cisplatin in breast cancer and its unattractive toxicity profile in palliative treatment warranted further study of platinum analogues in this disease. PATIENTS AND METHODS: Sixty-two patients with recurrent or metastatic breast cancer, 61 of whom had been previously treated with chemotherapy, were randomly assigned to therapy with either iproplatin (n = 32) or carboplatin (n = 30). Both platinum analogues were administered intravenously, iproplatin at a dose of 240 mg/m2 every 4 weeks and carboplatin at a dose of 450 mg/m2 every 5 weeks. RESULTS: Only two patients responded to iproplatin (7%) for durations of 21 and 61 weeks, and one patient responded to carboplatin (3%) for a duration of 64 weeks. All responses were complete. At the given dose schedules carboplatin was more myelosuppressive than iproplatin. Non hematologic toxicities included nausea and vomiting (93% vs. 90%), diarrhea (20% vs. 10%) and hemorrhage (16% vs. 10%) for iproplatin and carboplatin, respectively. Two patients developed alopecia with carboplatin. No renal toxicity was observed. CONCLUSIONS: Both iproplatin and carboplatin have limited activity in previously treated women with advanced breast cancer when given in conventional dosages. PMID- 8518221 TI - Usefulness of imaging ovarian cancer recurrence with In-111-labeled monoclonal antibody (OC 125) specific for CA 125 antigen. The INSERM Research Network (Nantes, Rennes, Reims, Vuillejuif, Saclay. AB - BACKGROUND: A progressive rise in serum CA 125 concentration during follow-up monitoring of ovarian cancer after treatment of primary tumor is suggestive of a recurrence. PATIENTS AND METHODS: A study was carried out in 19 patients with suspected recurrence of a previously treated ovarian carcinoma. All patients underwent ultrasonography (US), computed tomography (CT) and immunoscintigraphy (IS) using F(ab')2 fragments of indium-111-labeled OC 125 monoclonal antibody (specific for CA 125 antigen). The definitive diagnosis of recurrence was made on the basis of histological data obtained at surgery. RESULTS: In all 15 of the patients with recurrence, all three of the imaging methods had false negative results once. In 7 patients, only the IS method had positive results; six of these 7 benefited from a macroscopically total resection of the recurrence. IS was positive and concordant with US and/or CT in 7 further patients. Two of them benefited from a total resection of their recurrence. The usefulness of IS was more evident when serum CA 125 concentration was below 500 U/ml. The absence of recurrence was correctly indicated by IS and CT in 1 case and by IS associated with negative US and CT in 2 other cases. IS and CT were falsely positive in 1 case. CONCLUSION: Thus, immunoscintigraphy would appear to be an efficient method for detecting a recurrence early when limited involvement can make it possible for the surgeon to achieve total resection. PMID- 8518222 TI - Carboplatin, methotrexate, vinblastine and epirubicin (Carbo-MVE) for transitional cell bladder carcinoma. AB - BACKGROUND: MVAC is considered the most effective chemotherapy regimen for transitional cell bladder carcinoma. However, due to its significant toxic effects we substituted carboplatin for cisplatin and epirubicin for adriamycin in an attempt to produce the same response with less toxicity. PATIENTS AND METHODS: Twenty-seven patients with invasive transitional cell bladder carcinoma received Carbo-MVE: carboplatin (300 mgr/m2 d2), methotrexate (30 mgr/m2 d1, 15, 22), vinblastine (3 mgr/m2 d2, 15, 22) and epirubicin (30 mgr/m2 d2) every 4 weeks. RESULTS: There were 2 complete clinical responses (8.4%), 5 partial clinical responses (20.8%), 8 stabilizations (33.3%) and 9 progressions (37.5%). The overall clinical response rate was 29.2% (11%-47.4%, 95% CI), but 2 partial clinical remissions were not pathologically confirmed; were they to be considered as non-responses the response rate would fall even lower (20.8%). Toxicity was moderately severe, with 77.8% developing WHO grade III-IV granulocytopenia, 22.2% grade III-IV thrombocytopenia and 59.3% grade II-III vomiting. There were no toxic deaths nor any renal toxicity. CONCLUSIONS: Our results suggest that Carbo MVE is less active and at least as hematotoxic as multiagent CDDP-based regimens. PMID- 8518223 TI - Reversal of 5-fluorouracil-induced toxicity by oral administration of uridine. AB - BACKGROUND: Previous preclinical and clinical investigations have shown that the combined administration of 5-fluorouracil (5-FU) with delayed uridine can reverse side effects induced by 5-FU. This biochemical modulation-based combination may increase the therapeutic index of 5-FU. PATIENTS AND METHODS: Seven patients with advanced cancer were treated weekly with 5-FU at increasing dosages starting at a dose of 600 mg/m2. Five patients developed dose-limiting leukopenia, and two patients developed thrombocytopenia. At the dose-limiting toxicity level, 5-FU treatment was repeated and followed after 3 hours by oral uridine (5 g/m2 q 6 hr) during 72 hours. RESULTS: 5-FU-induced leukopenia was reversed for several weeks after the administration of oral uridine. However, thrombocytopenia was not reversed. Side effects of the combined treatment consisted of mild diarrhea in five of the seven patients. CONCLUSIONS: These data indicate that oral uridine can reduce the severity of 5-FU-induced myelosuppression. PMID- 8518224 TI - The management of bladder cancer--a case history. PMID- 8518225 TI - Gemcitabine in advanced renal cell carcinoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group. AB - BACKGROUND: Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) an anticancer agent with activity in preclinical models, was felt to be a promising new chemotherapy drug which warranted testing in patients with advanced renal cell carcinoma. METHODS: Eighteen patients with histologically proven metastatic or locally recurrent renal cell carcinoma and bidimensionally measurable disease were accrued to a phase II study of gemcitabine administered intravenously on days 1, 8 and 15 of a 28 day treatment cycle. Initial doses of gemcitabine were 800 mg/m2; doses in subsequent cycles were escalated to a maximum of 1250 mg/m2, toxicity permitting. RESULTS: One partial response was seen for a response rate of 6%. Hematologic toxicity was not severe with this dosing schedule; however, two patients developed dyspnea with bronchospasm after repeated injections of drug. CONCLUSIONS: The dose and schedule of gemcitabine employed results in only a modest response rate in patients with advanced renal carcinoma. Investigators should be aware of the possibility of dyspnea and bronchospasm developing shortly after gemcitabine administration. PMID- 8518226 TI - Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma. AB - BACKGROUND: Advanced pancreatic carcinoma (APC) is a rapidly fatal disease and an active chemotherapy with palliative effects and impact on patient survival is needed. 5 fluorouracil (5-FU) combined with cisplatin (CDDP) has a recognized synergistic activity, but its activity in APC has never been well established. METHODS: Forty eligible patients (pts) with measurable APC were treated in a phase II trial with 5-FU 1000 mg/m2/day from day 1 to day 5 by continuous intravenous infusion and CDDP 100 mg/m2 on day 2. Eighty percent of the pts (36/40) had metastatic disease, 32.5% (13/40) were previously treated and 65% (26/40) had performance states of 2 or 3. RESULTS: Of 38 evaluable pts, one had a complete response and 9 achieved partial responses; the overall response rate (RR) was 26.5% (95% CI: 12% to 40%). The median duration of responses was 10 months (range 4-18). The RR in non-pretreated pts was 32% A palliative effect was seen in 45% of pts (17/38). The median survival was 7 months and 12 pts (29%) were alive at 1 year. Leukopenia was the most important toxicity; 11 pts (27%) had a grade 4 leukopenia and 3 had neutropenic fever. CONCLUSIONS: The combination of CDDP and 5-FU in continuous infusion seems an active and well tolerated treatment in APC and will be compared to standard therapy in a multicentric randomized trial. PMID- 8518227 TI - Ophthalmic toxicity during carboplatin therapy. PMID- 8518228 TI - Relapse of acute myeloblastic leukaemia presenting as temporal bone chloroma with facial nerve paralysis. PMID- 8518229 TI - Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells. AB - The c-myc gene is thought to play a role in cell proliferation and differentiation; for example, constitutive expression of an exogenously introduced c-myc gene can inhibit differentiation in hematopoietic cell lines. Expression of the endogenous c-myc gene has now been monitored during the differentiation, and associated loss of proliferation, of ML-1 human myeloblastic leukemia cells: c-myc mRNA remains detectable, at decreased levels, during differentiation along the monocyte/macrophage pathway induced with 12-O tetradecanoylphorbol-13-acetate. c-myc protein also remains present, at undiminished levels, in mature, nonproliferative cells (assessed by immunoblotting and flow cytometry). The protein is, however, readily detectable in the cytoplasm of 12-O-tetradecanoylphorbol-13-acetate-induced cells, and some of this cytoplasmic c-myc exhibits a shift in electrophoretic mobility compared to the predominantly nuclear c-myc in uninduced cells. Furthermore, although c myc protein continues to be synthesized in the mature cells (assessed by metabolic labeling/immunoprecipitation), loss of the protein from the cytoplasm and accumulation in the nucleus are slowed (assessed by pulse-chase metabolic labeling). These findings suggest that, during the 12-O-tetradecanoylphorbol-13 acetate-induced differentiation and loss of proliferation of ML-1 cells, c-myc protein is regulated through alterations that affect its cytoplasmic/nuclear distribution rather than its total cellular content. PMID- 8518230 TI - Thyroid-stimulating hormone-regulated growth and cell cycle distribution of thyroid cells involve type I isozyme of cyclic AMP-dependent protein kinase. AB - Optimal growth and differentiation of normal rat thyroid FRTL5 cells depend strictly on the presence of thyroid-stimulating hormone (TSH). FRTL5 cells deprived of TSH cease dividing and become quiescent. Addition of TSH to quiescent cells, which activates the cyclic AMP-mediated pathway, is sufficient to stimulate cell entry into S phase of the cell cycle. We have previously shown that the differential expression of the two isozymes, type I and type II, of the cyclic AMP-dependent protein kinase (PKA) correlates with cell growth and differentiation of several rodent and human cell lines. We have studied the role of PKA in the TSH-regulated growth and cell cycle distribution of FRTL5 cells. Upon addition of TSH to FRTL5 cells deprived of hormone, a rapid induction of RI alpha mRNA species occurred within 30 min after treatment, reaching the levels of proliferating FRTL5 cells at 12 h. RII alpha mRNA levels slightly increased after TSH addition, whereas C alpha mRNA levels did not show major changes. Photoaffinity labeling of PKA receptor proteins showed that addition of TSH to quiescent FRTL5 cells induced a progressive increase in RI alpha levels starting at 6 h after stimulation, whereas RII alpha receptor levels increased only slightly. When FRTL5 cells were treated with an antisense oligodeoxynucleotide targeted against the RI alpha regulatory subunit, their growth was arrested, whereas an antisense against the RII alpha regulatory subunit produced only a mild growth inhibition. Moreover, exposure to the antisense RI alpha oligomer resulted in accumulation of cells in the G0-G1 compartment, as during TSH deprivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518231 TI - A potential transforming growth factor alpha/epidermal growth factor receptor autocrine circuit in placental cytotrophoblasts. AB - A potential autocrine loop involving transforming growth factor alpha (TGF-alpha) and the epidermal growth factor (EGF) receptor (EGFR) in benign placental cytotrophoblasts was examined. EGFR were localized to villous cytotrophoblasts and syncytiotrophoblasts in frozen sections throughout gestation using immunoperoxidase (IP) and autoradiography with 125I-EGF. EGF and TGF-alpha stimulated uptake of [3H]-thymidine in cultured cytotrophoblasts from first and second trimester placentae, demonstrating both functional EGFR and the mitogenic ability of either growth factor in these cells. Using IP, TGF-alpha was localized consistently throughout gestation to cytotrophoblasts with little or no staining of syncytiotrophoblasts in formalin-fixed sections. Variable staining of villous stromal cells and intense staining of maternal decidua were also observed. TGF alpha production by cultured cytotrophoblasts was confirmed in vitro via IP analysis of cytotrophoblasts cultured in serum-free media and enzyme-linked immunosorbent assay analysis of cytotrophoblast serum-free conditioned media. The results suggest that a TGF-alpha/EGFR autocrine loop stimulates proliferation of benign cytotrophoblasts. PMID- 8518232 TI - Intermediate cells during cytotrophoblast differentiation in vitro. AB - Differentiation of the human placental trophoblast cell involves a multistep process, with the generation of several distinct types of intermediate cytotrophoblast cells. Using a short term in vitro cell culture system and centrifugal elutriation, we studied the isolation and morphological and biochemical differentiation of these separated intermediate cell populations. Freshly isolated cell fractions, incubated for 24 h, are heterogeneous in their differentiation stages as determined by the secretion of the proteins chorionic gonadotropin alpha and beta, human placental lactogen, and pregnancy specific beta 1-glycoprotein. Maintenance in cell culture allows for the further differentiation of these intermediate cells and for syncytium formation. With the use of sequential trypsinizations, our data also suggest the parallel differentiation of cytotrophoblast cells into two distinct subsets: one which, through differentiation, gets committed to syncytium formation, and the other, which remains mononuclear despite high degrees of biochemical differentiation. These latter cells retain the capacity for syncytium formation when reintroduced into appropriate culture conditions. These findings refine the use of the term "intermediate cell" by previous investigators. We suggest that our in vitro system defines normal intermediate stages of trophoblast differentiation, and also serves as a model to simulate adverse conditions of syncytial degeneration or injury. PMID- 8518233 TI - Altered glycosylation of the env-sea oncoprotein inhibits intracellular transport and transformation. AB - The transforming gene product of the S13 avian erythroblastosis virus, env-sea, is a member of the growth factor receptor class of tyrosine kinases. The env-sea precursor protein gp155env-sea is proteolytically processed into the mature cleavage products gp85env and gp70env-sea, which are subsequently terminally glycosylated and transported to the cell surface. Previous studies have shown that the abnormal glycosylation of gp155env-sea induced by the carbohydrate processing inhibitor castanospermine blocks the proteolytic cleavage of gp155env sea and impairs its transforming ability. We have shown recently that an uncleaved but fully glycosylated sea-encoded protein retains the ability to transform chicken embryo fibroblasts, indicating that proteolytic processing is not essential for transformation by the env-sea tyrosine kinase. To address the question of how castanospermine blocks transformation by env-sea, differential sucrose gradient centrifugation was performed on env-sea-transformed cells treated with the inhibitor. This report shows that no surface forms of env-sea could be detected in inhibitor-treated cells, suggesting that castanospermine acts by blocking the transport of sea-encoded proteins to the cell surface. PMID- 8518234 TI - Epidermal growth factor receptor expression and function control cytotoxic responsiveness to tumor necrosis factor in ME-180 squamous carcinoma cells. AB - Tumor necrosis factor (TNF) induces dose-dependent but incomplete cytotoxicity in ME-180 cervical carcinoma cells, suggesting that TNF response heterogeneity exists within this cell line. To investigate cellular properties associated with TNF-mediated cytotoxicity, ME-180 cell variants were isolated that stably expressed complete resistance (ME-180R) or sensitivity (ME-180S) to TNF and were compared to the parental cell line. Analysis of 125I-TNF binding on variant and parental cells provided evidence for postreceptor regulation of TNF responsiveness. Epidermal growth factor (EGF) receptor expression in TNF resistant ME-180R cells was 3-fold higher than that expressed in the parental population and 4-fold higher when compared to TNF-sensitive ME-180S cells. High expression levels correlated with increased EGF receptor tyrosine kinase activity and receptor tyrosine phosphorylation. Southern and Northern blot analysis provided evidence of amplification and overexpression of the EGF receptor gene and its message in ME-180R cells which approached the content and alternate mRNA species expressed in A431 cells. Although 3-fold greater levels of total cellular EGF receptor protein were detected in ME-180R cell lysates, and its cell surface localization was confirmed by immunodetection, these cells were paradoxically unable to bind greater quantities of 125I-EGF or to express greater cytotoxic sensitivity to an EGF-diphtheria toxin fusion protein. Overall, these results suggest that expression of EGF receptor protein, its intrinsic tyrosine kinase activity, or its phosphotyrosine content may alter TNF cytotoxic signal transduction and control TNF responsiveness within the ME-180 cell line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518236 TI - What is the correct caesarean section rate? PMID- 8518235 TI - Posttranscriptional control of thymidine kinase messenger RNA accumulation in cells released from G0-G1 phase blocks. AB - In this study, we have utilized thymidine kinase (TK) mRNA induction as a model for investigating regulatory events at the G1-S boundary of the cell cycle. Using three independent methods for synchronizing diploid, nontumorigenic CHEF/18 cells, we found that the mechanism(s) underlying TK mRNA accumulation varied with the method of cell synchrony used. When cells were arrested by serum deprivation, both transcriptional and posttranscriptional controls contributed to the observed accumulation of TK mRNA at the G1-S boundary. When synchronized by isoleucine deprivation, mature TK mRNA and TK pre-mRNAs increased significantly at the G1-S boundary of the cell cycle with no detectable change in the rate of TK gene transcription. Following lovastatin treatment, which appears to arrest cells at a point very early in G1, posttranscriptional mechanisms were solely responsible for the subsequent accumulation of TK mRNA observed upon mevalonate repletion. We confirmed that transcriptional mechanisms were involved in TK mRNA regulation only when cells progressed from G0 into S phase using reporter genes transcribed from the heterologous human TK promoter. Taken together, these results indicate that posttranscriptional mechanism(s) are primarily responsible for regulating the abundance of TK mRNA during the cell cycle in CHEF/18 cells and further suggest uncoupling of transcriptional and posttranscriptional controls following different physiological conditions of cell cycle arrest. PMID- 8518237 TI - Hormone replacement therapy and malignancy. PMID- 8518238 TI - Breech delivery in very preterm and very low birthweight infants in The Netherlands. AB - OBJECTIVE: To study the relation between various perinatal factors and the sequelae of very preterm birth, applying logistic regression analysis. DESIGN: In a nationwide collaborative study in the Netherlands, perinatal and follow up data were collected on 899 liveborn singleton nonmalformed infants with gestational age less than 32 weeks or birthweight less than 1500 g born in 1983. MAIN OUTCOME MEASURES: Neonatal mortality rate and total handicap rates (minor and major) in surviving children at two years and five years of age. RESULTS: Comparing breech with vertex presentation, the odds ratio for neonatal mortality (adjusted for duration of pregnancy, birthweight, maternal hypertension and prolonged rupture of membranes) is 1.6 (P < 0.05). Comparing abdominal versus vaginal delivery, the odds ratio indicates equal risks. When breech and vertex presentation are analysed separately it appears that breech presenting infants have a significantly lower mortality risk when born by caesarean section compared with vaginal delivery. However, comparing abdominal versus vaginal delivery in breech presentation, the odds ratio for handicap at five years (0.9) is not significantly different from 1. CONCLUSION: The data presented suggest a reduced neonatal mortality rate in breech presenting infants born by caesarean section but because of the observational design of the study the statistical analysis described only identifies a possible trend and cannot prove the issue. PMID- 8518239 TI - Evaluation of six markers of haemostatic system in normal pregnancy and pregnancy complicated by hypertension or pre-eclampsia. AB - OBJECTIVE: To establish the plasma evolution of prothrombin fragments 1+2 (F 1+2), thrombin-antithrombin III complexes (TAT), fibrin fragment D-Dimers (DD), von Willebrand factor antigen (vWf), Type 1 plasminogen activator inhibitor antigen (PAI) and blood platelet count during normal pregnancy and to compare these values with those obtained in hypertensive or pre-eclamptic pregnancies. DESIGN: Cross-sectional study. SUBJECTS: Forty-seven healthy pregnant women with gestational age ranging between 5 and 40 weeks, and fourteen women with gestational age ranging between 25 and 38 weeks presenting with either gestational hypertension (n = 4) or pre-eclampsia (n = 10). Numbers of nulliparous women in the control, hypertension and pre-eclampsia groups were 13/47 (28%), 1/4 (25%) and 9/10 (90%), respectively. RESULTS: All six markers increased with gestational age in normal pregnant women (P < 0.01). Using the upper limit of 95% prediction interval obtained from regression curves as normality threshold, TAT showed the best sensitivity (71% vs < 30% for F1+2, DD, vWf, PAI and platelet count). CONCLUSION: TAT appears to be an interesting marker for detecting haemostatic system alterations in pregnancies complicated by hypertension or pre-eclampsia. A large prospective study to determine its clinical usefulness for such complicated pregnancies is currently in progress. PMID- 8518240 TI - Vaginal delivery after previous caesarean section: is X-ray pelvimetry necessary? AB - OBJECTIVE: To determine whether antepartum X-ray pelvimetry (XRP) reliably identified women suitable for a trial labour or repeat elective caesarean section after one previous section. DESIGN: A prospective controlled trial in which women were randomly allocated to either an antepartum XRP group who had XRP at 36 weeks gestation to determine mode of delivery, or a control group who had a trial labour without antepartum XRP. Following delivery, all controls had postpartum XRP. SETTING: Department of Obstetrics and Gynaecology, King Edward VIII Hospital, Durban, South Africa. SUBJECTS: Three hundred-six women with a history of one previous caesarean section. MAIN OUTCOME MEASURES: Mode of delivery, birthweight and maternal and perinatal mortality and morbidity in the two groups. RESULTS: In the antepartum XRP group, 23 of 144 (16%) of women delivered vaginally compared with 60 of 144 (42%) controls (P < 0.0001). Of the 84 women with adequate antepartum XRP only 23 (27.7%) delivered vaginally. In the control group, 33 of 60 (55%) women who had vaginal deliveries had inadequate postpartum XRP and would have had a caesarean section if this information was known in the antepartum period; 62 of 84 (74%) caesarean sections in the control group had adequate postpartum XRP. Birthweight of the infants was similar in the two groups. There were no maternal or perinatal deaths. Maternal morbidity was similar in the two groups. Neonatal morbidity was minimal. CONCLUSION: Antepartum XRP is not necessary prior to a trial labour in women with one previous caesarean section. It increases the caesarean section rate and is a poor predictor of the outcome of labour. PMID- 8518241 TI - The effect of early labour, maternal analgesia and fetal acidosis on fetal plasma oxytocin concentrations. AB - OBJECTIVE: To determine the effect of early labour, maternal analgesia and fetal hypoxia on circulating fetal oxytocin concentrations. DESIGN: Prospective observational study. SETTING: Delivery suite in a District General Hospital. SUBJECTS: Fifty women at term who did not require oxytocin administration or more than one form of analgesia. Study groups: vaginal delivery with (1) no analgesia, (2) pethidine, or (3) epidural analgesia. Caesarean section under regional analgesia (4) prior to, and (5) after the onset of labour. INTERVENTIONS: Samples of blood were collected from the umbilical artery (UA) and umbilical vein (UV) immediately after fetal delivery prior to placental separation or oxytocic administration. MAIN OUTCOME MEASURES: Plasma oxytocin (OT) concentration, umbilical vein pH, cystine aminopeptidase activity. RESULTS: The geometric mean UA-OT was significantly greater than UV-OT in all groups and was not altered by pethidine; however, epidural administration increased the UA-UV difference. The UA-UV difference at caesarean section was not significantly altered by the onset of labour. There was no correlation between UV pH and UA-UV plasma oxytocin. Cystine aminopeptidase activity was not detectable in UA and UV plasma. CONCLUSIONS: Fetal OT production is increased by epidural but not by pethidine analgesia. It is not influenced by the onset of labour or fetal hypoxia. PMID- 8518242 TI - Biparietal diameter and crown-rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome. AB - OBJECTIVES: 1. To compare the ultrasound biparietal diameter and crown-rump length of fetuses with and without Down's syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Down's syndrome. DESIGN: Matched case-control study. Cases were singleton Down's syndrome pregnancies with a biparietal diameter or a crown-rump length recorded. Five controls were matched to each case on: medical centre; the date of the ultrasound scan examination (within two years); gestational age measured as the number of days since the first day of the last menstrual period; and the ultrasound measure used (ie the biparietal diameter (the measure of choice), or the crown-rump length otherwise). If a woman had a serum screening test for Down's syndrome, the biparietal diameter or crown-rump length measurement had to be taken prior to the screening test so that the result of the test could not influence whether a scan was performed. SETTING: Ten antenatal screening centres in seven countries in Europe and North America. SUBJECTS: Two hundred and one women with singleton Down's syndrome pregnancies and 1005 women with unaffected singleton pregnancies. RESULTS: The median biparietal diameter of fetuses with Down's syndrome was identical to that among the controls (median difference 0.0 mm, 95% confidence intervals (CI) -0.5 to 0.5 mm). The estimates of gestational age based on biparietal diameter yielded a median gestational age less than that based on the women's last menstrual period: three days less for cases and two days less for controls; small but statistically significant differences probably reflected a minor systematic difference in the conversion of a biparietal diameter to a gestational age estimate. The median crown-rump length of fetuses with Down's syndrome was also identical to that among controls (median difference 0.0 mm, 95% CI-1.5 to 2.0 mm). There was no significant difference between the median gestational age estimate based on crown-rump length and that based on the women's last menstrual period. CONCLUSION: In antenatal screening for Down's syndrome the routine use of an ultrasound biparietal diameter or crown-rump length measurement to estimate gestational age will not adversely affect the detection rate. To avoid differences in gestational age estimates using the last menstrual period and the biparietal diameter influencing screening performance, separate medians should be derived for each serum marker using the two methods of estimating gestational age. The appropriate set of medians can then be used to calculate the multiple of the median value for each woman screened depending on the method used to estimate her gestational age. PMID- 8518243 TI - Clinical birthweight standards for a total population in the 1980s. AB - OBJECTIVE: To derive clinical standards for singleton birthweight in a population based on area of residence. DESIGN: Analysis of variables recorded in Aberdeen Maternity and Neonatal Databank, calculating for each birth a standardised birthweight score, taking account of determining factors. SUBJECTS: All singleton live births of 32 to 42 weeks gestation to Aberdeen City District residents from 1979 to 1983. RESULTS: Basic standards of birthweight are presented correcting for gestational age, sex of the baby and parity of the mother. Birthweight is not normally distributed and empirical data are presented rather than smoothed curves. Adjustment for maternal height is straightforward but adjustment for maternal weight must take account of the gestation at which the woman was weighed. A method of calculating the appropriate correction for height and weight is described in detail. CONCLUSION: Birthweight is not normally distributed at each week of gestation. Standardisation for parity, gestation and sex of the baby is essential, but adjustment for maternal size is complex. PMID- 8518244 TI - The effect on fetal arteriolar oxygen saturation resulting from giving oxygen to the mother measured by pulse oximetry. AB - OBJECTIVE: To determine if pulse oximetry could detect any changes in fetal arteriolar oxygen saturation resulting from maternal administration of oxygen. DESIGN: A prospective study comparing study comparing the fetal pulse oximetry reading before and after giving 27% and 100% oxygen to the mother. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: Labour ward, St. Jame's University Hospital, Leeds University, UK. SUBJECTS: Twelve fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURES: The change in fetal arteriolar oxygen saturation recorded by the pulse oximeter in response to oxygen administration to the mother. RESULTS: Twenty-seven percent oxygen increased the average fetal arteriolar oxygen saturation by 7.5%, the effect being reversed when the oxygen was withdrawn. One hundred percent oxygen increased fetal arteriolar oxygen saturation by 11% and when the oxygen was withdrawn oxygen saturation dropped by 10%. One hundred percent inspired maternal oxygen was more effective than 27%. The gradient of the fetal oxygen regression slope is steeper with 100% oxygen than 27% and it is steeper when oxygen is given compared to when it is withdrawn. This suggests that the fetus responds to the new placental oxygen gradient by accepting oxygen more rapidly than it gives it up. Using a quadratic regression model, it took 9 min for fetal oxygen saturation to reach its maximum value after giving the mother oxygen. CONCLUSION: This study confirms that a pulse oximeter is able to measure an increase in fetal arteriolar oxygen saturation when oxygen is administered to the mother. PMID- 8518245 TI - Transdermally administered oestradiol combined with oral medroxyprogesterone acetate: the effects on lipoprotein metabolism in postmenopausal women. AB - OBJECTIVE: To investigate the effects of two doses of transdermally applied oestradiol on lipid and lipoprotein metabolism in climacteric women. DESIGN: A randomised double blind cross-over comparison. SETTING: Departments of Obstetrics and Gynaecology, Ostra and Sahlgren's Hospital, Goteborg and Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Fifty-two women with climacteric symptoms were treated with oestradiol transdermally applied (50 micrograms and 100 micrograms/24 h). A daily dose of 5 mg oral medroxyprogesterone acetate was added 14 days each treatment cycle of four weeks. INTERVENTIONS: Blood samples were drawn after an overnight fast before and after four and eight months of treatment. MAIN OUTCOME MEASURES: Assays for serum triglycerides and cholesterol as well as low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol including the subfractions HDL2 and HDL3 were performed. RESULTS: Significant decrements were found in triglycerides and serum and LDL cholesterol during treatment with both doses. A modest rise in HDL2 cholesterol was observed after treatment with the 100 micrograms/24 h dose. CONCLUSIONS: The serum lipid and lipoprotein profile encountered in these women was similar to that reported with oral formulations except for a decrease in triglycerides. The metabolic differences between the two doses of transdermal oestradiol is probably of minor clinical significance in normal postmenopausal women. PMID- 8518246 TI - Maintained bone density at advanced ages after long term treatment with low dose oestradiol implants. AB - OBJECTIVE: To investigate whether the bone preserving effect of low dose oestrogen replacement therapy (20 mg oestradiol implanted subcutaneously every six months) persists during continuous long term treatment through advanced ages. DESIGN: Cross sectional clinical study of postmenopausal women treated with oestradiol implants as compared with nonusers matched for age. SETTING: Outpatient research unit at a university hospital. SUBJECTS: Thirty-five women with a mean age of 67 years (range 47-83 years) at the time of investigation who, after a prior hysterectomy, had been treated with oestradiol implants for climacteric symptoms for a mean period of 16 years (range 5.5-31 years). The results were compared with those in women matched for age and without any diseases or medications known to affect the bone metabolism. MAIN OUTCOME MEASURES: Bone mineral densities (BMD) in the distal forearm, vertebrae and hip analysed by study group, age and duration of treatment. RESULTS: Implant users had a median serum oestradiol concentration in the luteal range, 313 (range 126 1711) pmol/l, and premenopausal levels of follicle stimulating hormone (FSH). All women except one who were given the standard dose at the standard intervals had serum oestradiol levels below 650 pmol/l. Compared with nonusers, women treated with oestradiol implants had 20 to 25% higher BMD at all measurement sites: distal radius (P < 0.0001), lumbar vertebrae (P < 0.0002) and femoral neck (P < 0.0001). These differences also remained after adjustment for potential confounders (height, age at menarche, parity, smoking habits, physical exercise and education) (P < or = 0.01 at all sites). In a multiple regression analysis the negative effect of advancing age was more than compensated by the positive effect of increasing treatment duration with a higher BMD at all measurement sites in women with a longer as compared with shorter, duration of treatment; the regression coefficients were significant (P < 0.05) in the spine and hip measurements. CONCLUSIONS: Continuous long term treatment with low dose oestradiol implants yielding physiological levels of serum oestradiol preserves both compact and cancellous bone and the effect seems to persist into advanced ages without any inevitable age related bone loss. PMID- 8518247 TI - Concentration of endometrial protein PP14 in uterine flushings throughout the menstrual cycle in normal, fertile women. AB - OBJECTIVE: To determine the variation in concentration of endometrial protein PP14 in uterine flushings throughout the menstrual cycle comparing this to concentrations in plasma samples. DESIGN: Precise timing of all samples by the luteinising hormone surge. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Twenty-three regularly cycling, previously fertile volunteer women. INTERVENTIONS: Observational study; 10 ml of physiological saline was used to flush the uterine cavity once or serially in the cycle of the study. MAIN OUTCOME MEASURES: The measurement of PP14 levels by radioimmunoassay in uterine flushings and plasma samples. RESULTS: In uterine flushing, PP14 levels were not detectable in significant amounts in the proliferative phase and the early luteal phase; after day LH + 6, the concentration rises rapidly with a doubling time of only 6.6 to 14.6 h in the midluteal phase. In the late luteal phase, the concentrations in uterine flushing were over a hundred times higher than the corresponding plasma samples. CONCLUSIONS: The measurement of PP14 in uterine flushings is likely to be of greater value than the measurement in plasma samples; it may provide a valuable alternative to the evaluation of endometrial function. PMID- 8518248 TI - Destruction of CIN 1 and 2 with the Semm cold coagulator: 13 years' experience with a see-and-treat policy. AB - OBJECTIVE: To assess the efficacy of the Semm Cold Coagulator (100 degrees C) for CIN 1 and 2 applying a 'see and treat' policy. DESIGN: Retrospective review of women with CIN 1 and 2 seen and treated at their first visit when specific criteria were satisfied. SETTING: Colposcopy Clinic, Ninewells Hospital, Dundee. SUBJECTS: 485 women with CIN 1 and 680 women with CIN 2 confirmed by colposcopically directed biopsy and treated between 1 January, 1978 and 31 December, 1990. RESULTS: Overall, a 96.7% primary success rate with a single treatment (97.1% for CIN 1, 96.5% for CIN 2) and 99% overall success rate after one or more treatments with the cold coagulator. None of the women developed micro-invasive or invasive cancer and only 1.1% developed CIN 3. In 98.3% treatment was undertaken at their first and only colposcopy clinic attendance. Heavy vaginal bleeding occurred in 1.5% after treatment and 0.6% complained of a heavy vaginal discharge. One woman developed cervical stenosis which required dilatation because of dysmenorrhoea. CONCLUSION: Cold coagulation at 100 degrees C of CIN 1 and 2 proven by colposcopically directed biopsy using a 'see and treat' policy subject to specific conditions is a safe, cost effective, practical approach. It is more likely to return the cervix to sustained normality than withholding treatment and simply maintaining cytological surveillance, and it should prevent some of the invasive cancers that have been described in reports of management by cytological surveillance. PMID- 8518249 TI - Noninvasive test of microvascular endothelial function in normal and hypertensive pregnancies. AB - OBJECTIVE: To examine microvascular endothelial cell function in vivo in pre eclampsia. DESIGN: Iontophoresis of acetylcholine (Ach), which gives rise to endothelial cell dependent vasodilatation, and of sodium nitroprusside (SNP), which elicits vasodilatation independently of functioning vascular endothelium. SETTING: Sodersjukhuset, Stockholm, Sweden. SUBJECTS: Ten pre-eclamptic patients, ten healthy pregnant women and ten healthy nonpregnant women were examined. MAIN OUTCOME MEASURES: The degree of vasodilatation following iontophoretic administration of Ach compared with SNP was recorded with a laser Doppler technique, the data being analysed on a personal computer. RESULTS: Both Ach and SNP administration resulted in marked vasodilatation; the magnitude of the vasodilatation was similar in the three groups of women. CONCLUSION: Following iontophoretic administration of endothelial cell dependent or independent vasodilatators, laser Doppler measurement of blood flow demonstrated no microvascular endothelial cell dysfunction in pre-eclamptic women. PMID- 8518250 TI - Fetal angiotensin II levels and vascular (type I) angiotensin receptors in pregnancies complicated by intrauterine growth retardation. AB - OBJECTIVE: To investigate the status of the fetal renin-angiotensin system (RAS) in pregnancies complicated by severe intrauterine growth retardation (IUGR), and its possible relationship to elevated fetoplacental vascular resistance as indicated by abnormal umbilical artery Doppler flow velocity waveforms (FVW). DESIGN: Prospective survey of pregnancies falling into predefined categories and presenting at the Queen Mothers Hospital, Glasgow, over the study period. SUBJECTS: Effects of mode of delivery and gestational age were investigated using uncomplicated term pregnancies delivered vaginally (SVD group, n = 15) or by elective caesarean section (ECS group, n = 9), and normal pregnancies with spontaneous preterm onset of labour (PREM group, n = 6; normal birthweight for gestational age (31 weeks)). These groups were used as controls for the 13 IUGR cases delivered preterm (31 weeks) by caesarean section in the fetal interest. MAIN OUTCOMES MEASURES: Umbilical artery FVW, birthweight, cord venous angiotensin II concentration ([cv ANG II]), fetoplacental vascular ANG II receptor concentration. RESULTS: Cord venous angiotensin II concentration was similar to maternal values in the ECS group (31-101 pmol/l, 95% CI), but was elevated (81-288 pmol/l, P = 0.03) after vaginal delivery. The concentration of ANG II receptors (type AT1, dissociation equilibrium constant, 1.27 nmol/l) in placental primary/secondary stem vascular tissue was lower in the SVD group (18 44 fmol/mg membrane protein, 95% CI), compared with the ECS group (29-122 fmol/mg, P = 0.03) consistent with acute receptor down-regulation by the elevated ANG II levels. No effect of gestational age on receptor number was demonstrable (P = 0.13, PREM (premature delivery) vs ECS group). In the IUGR group, [cv ANG II] (94-378 pmol/l) was markedly elevated compared with the ECS controls (P = 0.001) but receptor concentration (28-84 fmol/mg) was not significantly altered (P = 0.13). No relationships between [cv ANG II] or receptor number and umbilical artery FVW could be identified. No changes in receptor affinity were observed. CONCLUSION: These results indicate activation of the fetal RAS in IUGR and suggest that responsiveness of the fetoplacental vasculature to the peptide is not diminished as would be expected from the elevated plasma ANG II levels. ANG II may contribute to the increased fetoplacental vascular resistance observed in this disorder, but does not apparently account for the abnormal umbilical artery FVW that is observed in a proportion of IUGR cases. PMID- 8518252 TI - Recurrent postpartum haemorrhage caused by endometrial carcinoma co-existing with endometrioid carcinoma of the ovary in a full term pregnancy. PMID- 8518251 TI - Plasma prostaglandin metabolite concentrations in normal and dysfunctional labour. AB - OBJECTIVE: To determine the concentrations of the metabolites of prostaglandin E2 (PGEM) and of prostaglandin F2 alpha (PGFM) prior to the onset of labour and during spontaneous labour, and to correlate the changes in concentrations of these metabolites with labour outcome. DESIGN: Longitudinal study throughout labour. SETTING: Labour ward of a large maternity unit. SUBJECTS: Seven primigravid and 11 parous women in the late third trimester with no signs of labour, and 17 primigravid and 11 parous women in spontaneous labour. INTERVENTIONS: Six of the primigravid women required augmentation with oxytocin because of dysfunctional labour. RESULTS: Before labour, parous women had significantly higher concentrations of both PGEM (P < 0.007) and PGFM (P < 0.006) compared with primigravid women. During labour, PGFM concentrations were significantly higher in both primigravid (P < 0.0002) and parous (P < 0.0001) women compared with the concentrations of these metabolites in women not in labour; the same was true for PGEM in primigravid (P < 0.003) but not in parous (P = 0.1) women. There was a small but significant increase (P < 0.02) in PGEM as labour progressed in both the normal groups. Amniotomy was associated with a significant increase in PGFM in primigravid and parous women (P < 0.002 and P < 0.009, respectively). The concentration of PGFM one hour following amniotomy correlated inversely with the amniotomy to delivery interval in both the normal primigravid (r = -0.624; P = 0.04) and the parous (r = 0.745; P = 0.021) groups. Women with dysfunctional labour showed no significant rise in PGEM or PGFM. Their PGFM concentrations were significantly lower than those seen in normal labour (P < 0.05). The concentration of PGFM in cord blood was significantly higher (P < 0.0001) in the parous women who laboured than in women delivered by elective caesarean section. There was no difference in the corresponding concentrations of PGEM (P = 0.9). CONCLUSIONS: These data show that spontaneous labour is associated with increased concentrations of prostaglandin metabolites in the maternal plasma, and are consistent with PGF2 alpha being an important stimulator of uterine contractility, with a relative deficiency of PGF2 alpha being associated with dysfunctional labour. PMID- 8518253 TI - Advanced cervical pregnancy treated with actinomycin-D. PMID- 8518254 TI - British caesarean section rates: have we reached a plateau? PMID- 8518255 TI - Outpatient investigation of postmenopausal bleeding. PMID- 8518256 TI - A simplified method of laparoscopic presacral neurectomy for the treatment of central pelvic pain due to endometriosis. PMID- 8518257 TI - Current cup designs for obstetric vacuum extraction. PMID- 8518258 TI - The effect of pH on release of PGE2 from vaginal and endocervical preparations for induction of labour. PMID- 8518259 TI - Long term follow up of women after hysterectomy with a history of pre-invasive cancer of the cervix. PMID- 8518260 TI - Randomised placebo controlled trial to assess the role of intracervical lignocaine in outpatient hysteroscopy. PMID- 8518261 TI - Antibiotic prophylaxis and caesarean section, commentary. PMID- 8518262 TI - Histological sampling of the endometrium--a comparison between formal curettage and the Pipelle sampler. PMID- 8518263 TI - Systematic and random errors associated with Johnston's cephalometric analysis. AB - This study examined intra- and interexaminer systematic and random errors associated with Johnston's cephalometric method of assessing skeletal and dental changes from pairs of radiographs. Data were obtained from the tracings of radiographs of 30 mixed dentition subjects, who had been treated to correct a Class II malocclusion. Measurements included molar and incisor crown movements relative to basal bone, apical base change, maxillary and mandibular displacement relative to the cranial base, and total molar and overjet reduction. In addition, the change in axial inclination of the incisors and molars was determined. A paired t-test for each pair of replicates for each measure was performed to examine inter- and intra-examiner bias. Estimates of the random error, the coefficient of reliability, and confidence limits (95 per cent level) of a single determination were undertaken. No systematic errors occurred between/within examiners for any linear or angular measure. Interexaminer random errors, based on the standard deviation of the mean difference between replicates, were greater than intra-examiner random errors for 12 out of 13 parameters. Measures assessing molar correction and overjet reduction had the least amount of random error variance within and across judges, while changes in mandibular position had the greatest. Because considerable random errors occurred, the Johnston analysis when used to assess skeletal changes, as well as individual molar and incisor movements, may have limited utility in clinical practice for the individual case. PMID- 8518264 TI - The influence of bracket material, ligation force and wear on frictional resistance of orthodontic brackets. AB - Planar static frictional phenomena were investigated for two types of ceramic and one type of stainless steel orthodontic bracket against rectangular stainless steel archwire. The brackets studied were 'Starfire' (single crystal aluminium oxide), 'Allure III' (polycrystalline aluminium oxide), and 'Dentaurum' (stainless steel). The investigative parameters were: bracket material, force of ligation and whether the brackets were new or 'worn'. Without exception, both types of ceramic bracket produced greater frictional resistance than the stainless steel brackets throughout testing. At a ligation force of 500 g, the Starfire bracket gave the greatest frictional resistance. At ligation forces of 200 and 50 g, the greatest frictional resistance was seen with Allure III. After a period of simulated wear, frictional resistance of Starfire tended to increase at the greatest ligation load while that of both ceramics decreased slightly at the two lower ligation loads. The ceramic brackets caused abrasive wear of the archwire surfaces and the consequent wear debris may have contributed to the changes in frictional resistance seen with Starfire and Allure III. Dentaurum brackets produced minimal frictional resistance in any test and negligible change with wear. PMID- 8518265 TI - The role of sandblasting on the retention of metallic brackets applied with glass ionomer cement. AB - A laboratory investigation of the shear bond strength of stainless steel brackets applied with glass ionomer cement (Ketac-Cem) and a conventional adhesive (Right on) is described. Sandblasting of the bracket base was undertaken in half of the sample bonded with Ketac-Cem and produced a significant reduction in the probability of failure relative to the unsandblasted sample. Brackets with sandblasted and unsandblasted bases, bonded with Ketac-Cem were subjected to mechanical fatigue in a ball mill for a total of 20 hours. Mean survival time (MST) was then calculated for each group and was found to be significantly improved by sandblasting of the bracket base (P < 0.01). PMID- 8518266 TI - Holograms and study models assessed by the PAR (Peer Assessment Rating) Index of malocclusion--a pilot study. AB - A selection of 30 sets of study models, representing a wide range of malocclusions, was drawn from the records of a clinical orthodontic department. Four holograms were made of each set of models; the study models and their corresponding holograms were then scored using the Peer Assessment Rating (PAR) Index of malocclusion. Significantly lower scores (P < 0.01) were obtained from the holograms, which were ascribed to three out of the seven components which make up the index. PMID- 8518267 TI - Process analysis of treatment provided by the hospital orthodontic service. AB - This investigation evaluates the influence of several process variables upon the number of attendances required to complete orthodontic treatment provided by the hospital service of England and Wales. The hospital records and study casts of 1630 patients were collected from 17 District General Hospital Departments. The study casts were analysed with the Peer Assessment Rating. The following information was collected from the hospital records; the patients' sex, the number of attendances required to complete treatment, the type of treatment provided and the operator. The data were analysed with multiple regression techniques. It appeared that the number of attendances was influenced by the pretreatment malocclusion severity, the type of treatment, the experience of the operator and the department from which the treatment was delivered. PMID- 8518268 TI - Personal audit in orthodontics. AB - The use of different criteria to assess outcome of orthodontic treatment makes it difficult to compare treatment from one individual practitioner to the next. This article describes a method for all dentists to use to record outcome for self audit purposes. A sample of 51 consecutively treated patients was assessed. On average, the mean percentage reduction in PAR score was 74 per cent. Eight per cent of patients were categorized as 'Worse or no different', 39 per cent 'Improved' and 53 per cent 'Greatly improved'. To achieve a good standard of orthodontic treatment it is proposed that the mean percentage reduction in PAR score should be greater than 70 per cent. The proportion of patients falling into the 'Worse or no different' category should ideally be less than 5 per cent. PMID- 8518269 TI - An evaluation of a hypertext system for computer-assisted learning in orthodontics. AB - A computer-assisted learning (CAL) package developed for undergraduate teaching in orthodontics is described. The programme makes use of the principle of 'hypertext'. The ability of undergraduates to learn from the programme is evaluated and compared to students taught conventionally. The opinions of the undergraduates who tried the programme are sought and discussed. PMID- 8518270 TI - An unerupted canine--an unusual diagnostic problem? AB - A case is reported in which the eruption of an upper canine was delayed as a result of the presence of a denticle. This remained undiagnosed until the age of 13 years. The paper illustrates the clinical and diagnostic problems associated with denticles in this region due to their position close to, but not actually in, the midline. PMID- 8518271 TI - Adhesives for orthodontic bonding: a comparison of materials available from the UK supply houses. PMID- 8518272 TI - Shortfall in applications to study dentistry in the UK. PMID- 8518273 TI - Orthognathic surgery and aesthetics: planning treatment to achieve functional and aesthetic goals. AB - Computerized video imaging is a valuable adjunct for communication with patients and planning orthognathic surgical treatment. The incorporation of adjunctive soft tissue procedures to enhance the final aesthetic result of orthognathic surgery is a valuable addition to the orthodontic and orthognathic treatment plan. This paper presents the use of video imaging techniques in the planning and execution of comprehensive functional and aesthetically orientated orthodontic and surgical treatment. PMID- 8518274 TI - Membrane partitioning: distinguishing bilayer effects from the hydrophobic effect. AB - The free energy of transfer of nonpolar solutes from water to lipid bilayers is often dominated by a large negative enthalpy rather than the large positive entropy expected from the hydrophobic effect. This common observation has led to the concept of the "nonclassical" hydrophobic effect and the idea that the "classical" hydrophobic effect may not drive partitioning in many bilayer systems. We show through measurements of the heat capacity changes associated with the partitioning of tryptophan side-chain analogs into lipid bilayers and into bulk cyclohexane that the hydrophobic effect plays a crucial role regardless of the large negative enthalpy. The results emphasize that bulk-phase measurements are inadequate for describing bilayer partitioning. The experimental approach described should be generally useful for analyzing the bilayer interactions of a broad range of biologically important molecules. PMID- 8518275 TI - Lipoxin A4 metabolism by differentiated HL-60 cells and human monocytes: conversion to novel 15-oxo and dihydro products. AB - Lipoxins are tetraene-containing eicosanoids that possess biological activity in several organ systems. To determine their route of further metabolism, [11,12 3H]lipoxin A4 was prepared and incubated with human neutrophils, promyelocytic leukemia (HL-60) cells, and adherent monocytes. Intact neutrophils and undifferentiated HL-60 cells did not significantly metabolize [11,12-3H]LXA4, while HL-60 cells differentiated with PMA to monocyte/macrophage lineage rapidly (< 15 s) transformed this eicosanoid. The major radiolabeled LXA4-derived metabolites were characterized by physical methods and were shown to be 15-oxo LXA4, 13,14-dihydro-15-oxo-LXA4, and 13,14-dihydro-LXA4. Substrate competition with cell-free supernatants from differentiated HL-60 cells suggests that lipoxins compete for 15-hydroxyprostaglandin dehydrogenase activity or an equivalent enzyme system. In addition, adherent monocytes exposed to [11,12 3H]LXA4 rapidly metabolized (> 60% within 30 s) the label to its oxo and dihydro derivatives. These results indicate that, unlike leukotrienes, LXA4 is subject to dehydrogenation and reduction of its conjugated tetraene to form triene containing products. Moreover, they suggest that monocytes participate in lipoxin metabolism in their local milieu. PMID- 8518276 TI - Crystallographic determination of the active site iron and its ligands in soybean lipoxygenase L-1. AB - Five ligands of the active site iron atom in soybean lipoxygenase L-1 have been identified from the electron density map of the crystallized enzyme. The position of the iron atom can be readily and independently located from an anomalous difference electron density map. The ligands identified are His-499, His-504, His 690, Asn-694, and Ile-839, the carboxy-terminal residue. Our previous view that these three histidines are essential for activity and binding of iron, based on site-specific mutation studies, is confirmed. A sixth protein ligand is not present, and the sixth coordination site opens into a wide cleft. The structure of the soybean lipoxygenase was solved by multiple anomalous isomorphous replacements. PMID- 8518277 TI - Mutations in the catalytic domain of factor IX that are related to the subclass hemophilia Bm. AB - Hemophilia Bm, a variant of hemophilia B, results in a marked increase in the ox brain prothrombin time. Mutations known to cause hemophilia Bm occur at residue 180, 181, or 182 near the amino terminus of the heavy chain and at residue 311, 364, 368, 390, 396, or 397 near the activation site of factor IX (Giannelli et al., 1990). In this study we replaced factor IX residues 181, 182, and 390 in separate experiments by site-directed mutgenesis. Valine 181 was replaced by isoleucine or alanine, and valine 182 was replaced by alanine or glycine. Alanine 390 was replaced by valine or aspartic acid. Recombinant factor IXs were expressed in human kidney 293 cells and purified by absorption and elution from a conformational specific monoclonal antibody column. The results show that factor IX Bm is a function not only of the position of the mutated amino acid but also of the particular amino acid substituted. For example, when valine 181 or 182 was replaced by small hydrophobic amino acids (alanine and glycine), factor IXs were found to have significantly decreased clotting activity. Unlike the naturally occurring mutations (Val181 --> Phe181 or Val182 --> Leu182), however, the small amino acid replacements did not result in prolonged ox brain prothrombin times. Surprisingly, the Ala390 --> Asp390 exchange did not affect clotting activity or binding to the macromolecular inhibitor antithrombin III. The Ala390 --> Val390 exchange resulted in loss of both clotting activity and binding to antithrombin III. These results suggest that residue 390 is not directly involved in binding to antithrombin III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518278 TI - Protein-heme interactions in hemoglobin from the mollusc Scapharca inaequivalvis: evidence from resonance Raman scattering. AB - Resonance Raman spectra of the Scapharca inaequivalvis homodimeric hemoglobin (HbI) have been measured for the ligand-bound and ligand-free ferrous forms of the protein. In the deoxy derivative, the iron-histidine (Fe-His) stretching mode, proposed as a marker of the oxygen affinity and a conduit linking the hemes to the subunit interface, gives rise to a Raman peak centered at 203 cm-1, an unusually low frequency compared to that reported for other hemoglobins and myoglobins. In the CO-bound derivative, three isotope-sensitive lines at 517, 583, and 1945 cm-1 have been assigned to the Fe-CO stretching, Fe-C-O bending, and C-O stretching modes, respectively. From the frequencies of these modes and from their relative intensities, the Fe-C-O geometry appears to be tilted from axial coordination and shows a bending angle which has been estimated to be about 171 +/- 5 degrees. For the oxygen derivative, only one isotope-sensitive peak has been detected at 570 cm-1, in line with the values found for myoglobin and other hemoglobins. Resonance Raman spectra of HbI modified with p (chloromercuri)benzoate (PMB) at Cys92 have been measured in parallel with those of the native protein. Despite the large increase in oxygen affinity produced by the PMB modification, the frequency of the Fe-His stretching mode is unshifted in the deoxy derivative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518279 TI - Peptide models of protein folding initiation sites. 1. Secondary structure formation by peptides corresponding to the G- and H-helices of myoglobin. AB - Myoglobin has been extensively studied as a model system for protein folding in vitro. As part of an ongoing study of myoglobin folding, we have synthesized a series of peptide fragments corresponding to portions of the sequence of the sperm whale protein. The conformational preferences of these peptides have been investigated by circular dichroism and nuclear magnetic resonance spectroscopy in aqueous solution. In this paper we describe the folding propensities of two peptides (Mb-G and Mb-H), corresponding to the G- and H-helix segments of the myoglobin sequence. The Mb-G peptide shows evidence of a very small population of helical conformations in aqueous solution, both by CD and NMR. By contrast, the monomeric Mb-H peptide is found by CD to adopt a significant population (ca. 30%) of ordered helix and by NMR to populate helical conformations in rapid dynamic equilibrium with unfolded states. The Mb-H peptide undergoes a well characterized, concentration-dependent monomer-tetramer equilibrium. At peptide concentrations greater than 1 mM there is an increase in the population of helix, to approximately 85% according to the CD spectrum, through self-association to form a tetramer. Both medium-range NOE connectivities and a CD spectrum characteristic of ordered helix are observed at low peptide concentrations, establishing that helical conformations are present in the monomeric state of Mb H. The relative helicity at various sites throughout the Mb-H peptide has been estimated using a novel method for assessing the distribution of helical populations based on the relative magnitudes of medium-range d alpha beta (i,i+3) NOE connectivities. The population of ordered helix is seen to be highest in the center of the peptide sequence; the ends of the peptide show evidence of pronounced fraying. PMID- 8518280 TI - Peptide models of protein folding initiation sites. 2. The G-H turn region of myoglobin acts as a helix stop signal. AB - A series of peptide fragments of sperm whale myoglobin, corresponding to segments of the region between the G- and H-helices of the protein, have been synthesized and their conformational preferences investigated using circular dichroism and nuclear magnetic resonance spectroscopy in aqueous solution and in solvent mixtures containing water and trifluoroethanol. The smallest fragment, Mb-GH5, a five-residue peptide with the sequence HPGDF corresponding to the connecting loop between the two helices in the folded protein, adopts highly populated turn conformations in aqueous solution. A 25-residue peptide, Mb-GH25, containing the same sequence flanked by contiguous segments of the G- and H-helix sequences, was also found to contain a high proportion of conformers with a turn in this region. No helix formation was observed in the flanking sequences in water solution, either in Mb-GH25 or in control 10-residue peptides (Mb-G10 and Mb-H10) with sequences corresponding to the G- and H-helix segments. No additional helicity above that of the sum of the components was observed for Mb-GH25, indicating that a helical hairpin structure is not formed in the monomeric peptide in aqueous solution. In the presence of TFE, ordered helix is formed in Mb-GH25 according to the CD spectrum, and NMR spectra indicate that this is localized in the N terminal portion of the peptide. NOESY spectra clearly show that the turn conformation is retained under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518281 TI - Peptide models of protein folding initiation sites. 3. The G-H helical hairpin of myoglobin. AB - As part of an extensive dissection of the folding pathway of myoglobin, a series of peptides corresponding to fragments of sperm whale myoglobin have been synthesized, and their conformational preferences investigated using circular dichroism and nuclear magnetic resonance spectroscopy in aqueous solution and in solvent mixtures containing water and trifluoroethanol. The behavior of short fragments corresponding to the sequences of the G- and H-helices of myoglobin and to the turn region between these helices has been described in accompanying papers. At the next level of complexity, peptide model compounds have been synthesized to explore the longer-range interactions which may take place in protein folding after initial secondary structure formation has occurred. A series of disulfide-bridged dimeric peptides containing the complete sequences of the G- and H-helices of myoglobin were synthesized and their conformational preferences examined. CD spectra indicate that disulfide-bridged peptides consisting of two H-helix sequences (Mb-HssH) and of one G- and one H-helix (Mb GssH) are highly helical in water solution, as a result of intermolecular association. A 51-residue peptide, Mb-GH51, encompassing the entire G-H helical hairpin of myoglobin, including the turn sequence between the two helices, has been successfully synthesized by standard methods. This peptide was designed to be monomeric in aqueous solution. Mb-GH51 does not appear from CD spectra to contain any additional helix in water solution above what would be expected from an equimolar mixture of the G- and H-helix peptides. NMR spectra indicate that the turn conformation observed in shorter peptide fragments is retained in Mb GH51 in high population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518282 TI - Glycosphingolipid-enriched, detergent-insoluble complexes in protein sorting in epithelial cells. AB - In simple epithelial cells, the delivery of apical and basolateral proteins to the cell surface is mediated by sorting in the trans-Golgi network and transport via separate vesicular carriers. In order to identify the molecular machinery involved in protein sorting, we have recently studied a detergent-insoluble complex in Madin-Darby canine kidney (MDCK) cells, following CHAPS extraction of exocytic carrier vesicles, specifically including the apical marker protein influenza hemagglutinin (HA). Previously, a Triton X-100 insoluble membrane residue that was enriched in glycosylphosphatidylinositol-anchored (GPI) proteins and glycolipids was characterized and implicated in transport to the apical cell surface [Brown, D., & Rose, J. (1991) Cell 68, 533-544]. In this report, the protein compositions of the CHAPS and Triton complexes have been compared by two dimensional gel analysis. Only a few major membrane proteins are found in the complexes. The protein compositions are qualitatively similar, but differ quantitatively in the individual components. The CHAPS complex is depleted of GPI linked proteins and retains a minor fraction of lipids similar in composition to that of the Triton X-100 insoluble complex. We propose that in vivo the complexes form part of a sorting platform that mediates protein segregation and delivery to the apical cell surface. PMID- 8518283 TI - The role of cysteine residues of spinach ferredoxin-NADP+ reductase As assessed by site-directed mutagenesis. AB - To investigate the functional role of the cysteine residues present in the spinach ferredoxin-NADP+ oxidoreductase, we individually replaced each of the five cysteine residues with serine using site-directed mutagenesis. All of the mutant reductases were correctly assembled in Escherichia coli except for the C42S mutant protein. C114S and C137S mutant enzymes apparently showed structural and kinetic properties very similar to those of the wild-type reductase. However, C272S and C132S mutations yielded enzymes with a decreased catalytic activity in the ferredoxin-dependent reaction (14 and 31% of the wild type, respectively). Whereas the C132S was fully competent in the diaphorase reaction, the C272S mutant flavoprotein showed a 35-fold reduction in catalytic efficiency with respect to the wild-type enzyme (0.4 versus 14.28 microM-1 s-1) due to a substantial decrease of kcat. NADP+ binding by the C272S mutant enzyme was apparently quantitatively the same (Kd = 37 microM) but qualitatively different, as shown by the differential spectrum. Stopped-flow experiments showed that the enzyme-FAD reduction rate was considerably decreased in the C272S mutant reductase, along with a much lower yield of the charge-transfer transient species. It is inferred from these data that the charge transfer (FAD-NADPH) between the reductase and NADPH is required for hydride transfer from the pyridine nucleotide to flavin to occur with a rate compatible with catalysis. PMID- 8518284 TI - Secondary structure and backbone resonance assignments of the periplasmic cyclophilin type peptidyl-prolyl isomerase from Escherichia coli. AB - Proton, carbon-13, and nitrogen-15 sequence-specific backbone assignments have been obtained for the periplasmic cyclophilin type cis-trans peptidyl-prolyl isomerase from Escherichia coli (167 residues, M(r) = 18,244). Assignments were obtained using both 1H, 13C, and 15N triple-resonance and 1H and 15N double resonance three-dimensional (3D) NMR spectroscopy at pH 6.2, 25 degrees C. Complete or partial residue-specific assignments have been obtained for 165 of the 167 residues. The secondary structure has been characterized using long- and medium-range NOEs. The protein consists of an eight-stranded anti-parallel beta sheet and two helices. The overall topology of E. coli cyclophilin is similar to that of human T-cell cyclophilin. Sequence alignment with human T-cell cyclophilin based on secondary structure homology implicates several residues in E. coli cyclophilin that may be crucial for binding the peptide substrate AC-A-A P-A-AMC and the immunosuppressive drug cyclosporin A. PMID- 8518285 TI - Effect of chloride on oxygen binding to crystals of hemoglobin Rothschild (beta 37 Trp-->Arg) in the T quaternary structure. AB - Oxygen binding to crystals of hemoglobin Rothschild (beta 37 Trp-->Arg) in the T quaternary structure has been investigated by polarized absorption microspectrophotometry. These crystals were grown from poly(ethylene glycol) solutions containing low concentrations of salt. In the absence of chloride, they have a significantly higher oxygen affinity than crystals of human hemoglobin A grown in a similar manner, and exhibit Hill coefficients lower than 1. There is no Bohr effect from pH 6 to 9. We have found that chloride decreases the oxygen affinity of Hb Rothschild crystals, an effect which is absent in crystals of HbA. This dependence of affinity on chloride is almost certainly associated with the chloride binding sites which have been localized crystallographically at the mutant arginine residues (Kavanaugh et al., 1992). Since chloride binding appears to lower the oxygen affinities of both the alpha and beta chains, the linkage between the binding of oxygen and the dissociation of chloride results in significant cooperativity in oxygen binding to the crystals. PMID- 8518286 TI - Kinetic mechanisms of the A and B isozymes of O-acetylserine sulfhydrylase from Salmonella typhimurium LT-2 using the natural and alternative reactants. AB - The resonance-stabilized quinonoid 5-mercapto-2-nitrobenzoate (TNB) is a substrate for O-acetylserine sulfhydrylase-A (OASS-A) and -B (OASS-B), giving rise to the product S-(3-carboxy-4-nitrophenyl)-L-cysteine (S-CNP-cysteine) as confirmed by ultraviolet-visible and 1H NMR spectroscopies. A comparison of the kinetics of OASS-A and OASS-B indicates that the mechanism proceeds predominantly via a bi-bi ping pong kinetic mechanism as suggested by an initial velocity pattern consisting of parallel lines at low concentrations of reactants, but competitive inhibition by both substrates as the reactant concentrations are increased. Thus, in the first half-reaction, O-acetyl-L-serine (OAS) or beta chloro-L-alanine (BCA) is converted to alpha-aminoacrylate in Schiff base with the active site pyridoxal 5'-phosphate, while in the second half-reaction cysteine (with sulfide as the reactant) or S-CNP-cysteine (with TNB as the reactant) is formed. The ping pong mechanism is corroborated by a qualitative and quantitative analysis of product and dead-end inhibition. Product inhibition by acetate is S-parabolic noncompetitive. These data are consistent with acetate reversing the first half-reaction and producing more free enzyme to which acetate may also bind. Thus, there may be some randomness to the mechanism at high concentrations of the nucleophilic substrate. PMID- 8518287 TI - Identification and in vitro expression of mutations causing dihydropteridine reductase deficiency. AB - Six mutations resulting in the recessive inherited disorder dihydropteridine reductase deficiency are reported, five of which are previously unknown. Two are nonsense mutations, resulting in premature termination of the protein, with the remaining four being missense mutations. The mutations found lie in the middle to 3' end of the dihydropteridine reductase reading frame, with the exception of one mutation which lies at codon 23, which is the only mutation found in more than one patient. The mutation pattern can be described as heterogeneous. The wild type and several of the mutant DHPR cDNA's were expressed in E. coli and the proteins purified and examined by a variety of techniques, including calculation of kinetic constants. One mutation (Gly23-->Asp) results in completely inactive protein, while a second (Trp108-->Gly) has substantial activity but does not completely dimerize. Both this mutant and a third, His158-->Tyr, are extremely susceptible to in vitro protease digestion, indicating that their three dimensional structure has been altered. The protein studies underline the heterogeneous nature of DHPR mutations, in that the effects of different amino acid substitutions on the DHPR enzyme are varied. PMID- 8518288 TI - Mechanism of adenylate kinase. What can be learned from a mutant enzyme with minor perturbation in kinetic parameters? AB - The structural and functional roles of threonine-23 in the chicken muscle adenylate kinase (AK) were investigated by site-directed mutagenesis coupled with proton nuclear magnetic resonance (NMR) and phosphorus stereochemistry. The residue is potentially important because it is conserved among all types of AK and is part of the consensus P-loop sequence, 15GXPGXGKGT23. A mutant enzyme T23A (replacing threonine-23 with alanine) was constructed. Analyses of conformational stability and proton NMR indicate that the side chain of this residue contributes little to the structure of AK, which suggests that the side chain of Thr-23 does not play a structural role. The steady-state kinetic data of the mutant enzyme T23A showed no change in kcat and only 5-7-fold increases in Km and dissociation constants. Such minor changes in kinetic data are insufficient to suggest a functional role of Thr-23. However, two-dimensional NMR analyses of WT.MgAP5A and T23A.MgAP5A complexes indicated that the side chain of Thr-23 is in proximity to the adenine ring of the ATP moiety in the WT.MgAP5A complex in solution. In addition, T23A showed a significant perturbation in the stereospecificity toward the diastereomers of (Rp)- and (Sp)-adenosine 5'-(1-thiotriphosphate) (ATP alpha S), with the Rp/Sp ratio increased from < 0.02 in wild-type to 0.37 in T23A. Detailed 31P NMR analysis indicated that the stereospecificity at the AMP site was not perturbed. These results suggest that the side chain of Thr-23 is involved in catalysis, most likely via a hydrogen bonding interaction Thr-OH...O P alpha(ATP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518289 TI - DNA internal motions within nucleosomes during the cell cycle and as a function of ionic strength. AB - We have used 31P NMR spectra to show that DNA internal motions are greatly hindered within oligonucleosomes. The fluctuations seem to be a function of both the cell cycle and the number of nucleosomes interlinked. Namely, the resonance areas, directly related to unbound phosphate, are consistently smaller in M-phase than in S-phase; at the same time, the resonance line width, inversely related to base plane, deoxyribose, and phosphate internal motions, is consistently larger in mononucleosomes than in oligonucleosomes. In all cases, the removal of chromosomal proteins, by a progressive increase of ionic strength up to 2 M NaCl, increases the internal motion, as monitored by a decrease in line width toward that of free DNA. While for both oligo- and mononucleosomes in S-phase the decrease in line width is strictly correlated to a sharp increase in resonance area, in M-phase it is not, with the 31P resonance area rather low even at 2.0 M NaCl extraction. Similarly, while S-phase 31P line widths steadily grow from mono to oligonucleosomes, in M-phase they do not. Moreover, the increase of the ionic strength to 0.6 M NaCl, as compared to 0.35, 1.2, and 2 M NaCl, displays significant variations on 31P line width and resonance area, independent of the cell cycle phase and the number of nucleosomes interlinked. These observations agree with earlier suggestions on the differential role of the various chromosomal protein subfractions, known to preferentially dissociate at the different ionic strengths in question, in the sealing of mononucleosomes and in the overall stability of polynucleosomes. PMID- 8518290 TI - The divalent cation is obligatory for the binding of ligands to the catalytic site of secreted phospholipase A2. AB - The divalent cation requirement for partial reactions of the catalytic turnover cycle during interfacial catalysis by pig pancreatic phospholipase A2 (PLA2) is investigated. Results show that the specific role of calcium in all the events of the catalytic cycle at the active site is not shared by other divalent cations. Cations such as calcium, barium, and cadmium bind to the enzyme in the aqueous phase. The active-site-directed ligands (substrate, products, and transition state mimics) do not bind to the enzyme in the absence of a divalent cation. The synergistic binding of such ligands to the active site of PLA2 bound to the interface is, however, observed only in the presence of isosteric ions like calcium and cadmium, but not with larger ions like strontium or barium. The equilibrium constants for ligands bound to the enzyme in the presence of calcium and cadmium are virtually the same. However, only calcium supports the catalytic turnover; the rate of hydrolysis in the presence of cadmium is less than 1% of that observed with calcium. The role of divalent ions on the interfacial catalytic turnover cycle of PLA2 is not only due to the cation-assisted binding of the substrate but also due to its participation in the chemical step. Other roles of divalent ions in the events of interfacial catalytic turnover are also identified. For example, the binding of the enzyme to the interface is apparently promoted because the divalent cation is required for the sequential step, i.e., the binding of the substrate to the active site of PLA2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518291 TI - Optimal kinetic design of enzymes in a linear metabolic pathway. AB - The rate equations for a sequence of enzymic reactions conforming to Michaelis Menten kinetics have been analyzed in order to establish what kinetic design optimizes the steady-state reaction flux for a given total concentration of enzymes and a given average magnitude of true and apparent first-order rate constants in the reaction system. Analytical solutions are presented which have been derived with the assumptions that the concentration of the first substrate in the pathway represents a fixed parameter and that no diffusional constraints come into operation. The solutions prescribe that reaction flux in the examined system becomes optimal when all of the enzymes are present at equal active-site concentrations. The optimal kinetic design of each enzyme reaction is characterized by forward (true or apparent) first-order rate constants of equal magnitude and reverse rate constants of equal magnitude. This means that the optimal kinetic design of the examined pathway is highly uniform, individual enzymes being likely to exhibit optimal V values differing by a factor less than 5 and optimal Km/[S] values falling within the range 0.3-2. PMID- 8518292 TI - On the involvement of intramolecular protein disulfide in the irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by diallyl disulfide. AB - Treatment with diallyl disulfide, a constituent of garlic oil, irreversibly inactivated microsomal and a soluble 50 kDa form of HMG-CoA reductase. No radioactivity was found to be protein-bound on treating the soluble enzyme with [35S]diallyl disulfide, indicating the absence of the mixed disulfide of the type allyl-S-S-protein. SDS-PAGE and Western blot analyses of the diallyl-disulfide treated protein showed no traces of the dimer of the type protein-S-S-protein, but clearly indicated BME-reversible increased mobility, as expected of an intramolecular protein disulfide. The sulfhydryl groups, as measured by alkylation with iodo[2-14C]acetic acid, were found to decrease in the diallyl disulfide-treated enzyme protein. Tryptic peptide analysis also gave support for the possible presence of disulfide-containing peptides in such a protein. It appears that diallyl disulfide inactivated HMG-CoA reductase by forming an internal protein disulfide that became inaccessible for reduction by DTT, and thereby retaining the inactive state of the enzyme. PMID- 8518293 TI - Phosphonate inhibitors of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. AB - Several bisphosphonates were examined as inhibitors of yeast GPD (glyceraldehyde 3-phosphate dehydrogenase, EC 1.2.1.12) and PGK (phosphoglycerate kinase, EC 2.7.2.3). The phosphonomethyl analog of 2-deoxy-1,3-bisphosphoglycerate (i.e., 2 oxo-1,5-bisphosphonopentane, 2-oxo-PC5P) is a good inhibitor of PGK (Ki = 0.2 +/- 0.08 mM at pH 8.5, 27 degrees C) and a poor inhibitor of GPD (Ki = 20 +/- 1 mM, pH 8.5). The shorter, butane, analog (2-oxo-PC4P) binds more tightly to PGK (Ki = 84 +/- 6 microM), and about equally well to GPD, as does 2-oxo-PC5P. The 2-oxo bisphosphonates bind to PGK more tightly (by approx. 4 kJ/mol) than do the corresponding non-carbonyl analogues (1,4-bisphosphonobutane and 1,5 bisphosphonopentane). PMID- 8518294 TI - An investigation into the stability of alpha-crystallin by NMR spectroscopy; evidence for a two-domain structure. AB - The stability of bovine lens alpha-crystallin with respect to temperature, pH and urea has been investigated by 1H and 31P-NMR spectroscopy. The 1H and 31P-NMR spectra of alpha-crystallin show little change with temperature up to 75 degrees C, indicating that alpha-crystallin has great thermal stability and does not undergo any major change in structure with temperature. 1H spectral studies of alpha-crystallin and its isolated alpha A and alpha B subunits reveal a marked difference in the stability of these species. It is found that, at pH 2.5, alpha A-crystallin adopts a native conformation whereas alpha B-crystallin is denatured. On the other hand, the two subunits when part of the total alpha crystallin aggregate adopt a native conformation at pH 2.5, but in the presence of 0.1 M glycine the alpha B subunits become denatured. Thus, alpha A-crystallin and total alpha-crystallin are more stable species than alpha B-crystallin and, in total alpha-crystallin, there is an interaction between the compact domains of the alpha A and alpha B subunits that leads to enhanced stability. Finally, changes in the 1H and 31P-NMR spectra of alpha A-crystallin and alpha B crystallin in the presence of varying concentrations of urea are consistent with a two-domain model for alpha-crystallin subunits with the C-terminal domain being less stable and unfolding first in the presence of urea. PMID- 8518296 TI - Inactivation before significant conformational change during denaturation of papain by guanidine hydrochloride. AB - During denaturation by GuHCl, papain shows a rapid decrease in activity with increasing concentrations of the denaturant followed by an intermediate stage of relatively little change from 1 to 2 M before complete inactivation at 4 M GuHCl. At GuHCl concentrations lower than 2 M, enzyme activity is more sensitive to GuHCl than noticeable conformation changes as followed by fluorescence and CD measurements. Kinetics of GuHCl inactivation were studied by following the substrate reaction in the presence of denaturant and the apparent rate constants thus obtained were found to be only slightly higher than those for conformational changes. However, apparent inactivation rate constants obtained in the presence of saturating concentration of substrate are actually inactivation constants for the ES complex. The inactivation rates at different substrate concentrations were, therefore, followed and the microscopic inactivation rate constants for the free enzyme obtained (Tsou, C.L. (1988) Adv. Enzymol. 61, 381-436). It was found that substrate protects strongly against inactivation and at the same GuHCl concentration, the inactivation rate of the free enzyme is 100-fold higher than that of unfolding. The above results show that the activity of papain is more sensitive to GuHCl than its overall conformation and like the enzymes previously studied in this laboratory, its active site is more flexible than the enzyme molecule as a whole. PMID- 8518295 TI - L-pipecolic acid oxidation in rat: subcellular localization and developmental study. AB - By using a sensitive radioactive assay method, we present here evidence that L pipecolic acid oxidase is localized in both mitochondria and peroxisomes of rat liver. Brain white matter contained a more than 2-fold higher activity of L pipecolic acid oxidation than the brain cortex. Suborganellar fractionation studies indicate that while the enzyme is a matrix protein in mitochondria, it is membrane-associated in peroxisomes. Both rotenone and antimycin A completely inhibited the enzyme activity in mitochondria but not in peroxisomes. The enzyme was shown to be inducible in mitochondria and peroxisomes of rat liver and brain tissues by glucagon and di-(2-ethylhexyl)phthalate, respectively. We report here for the first time the developmental aspects of L-pipecolic acid oxidation activity in rat liver and brain tissues. L-Pipecolic acid oxidase activity was detectable in whole rat embryo at 10 days of gestation, suggesting active L pipecolic acid metabolism early during development. In both liver and brain tissues L-pipecolic acid oxidation activity was highest at 15 days of gestation and decreased with age in prenatal and postnatal conditions. PMID- 8518297 TI - Inactivation precedes conformation change during thermal denaturation of adenylate kinase. AB - During the thermal denaturation of rabbit muscle adenylate kinase, the extents and rates of both unfolding and aggregation are dependent on protein concentration. Under identical conditions, inactivation takes place at a lower temperature than noticeable conformational changes and aggregation as measured by fluorescence, second derivative absorption spectroscopy, far ultraviolet circular dichroism and light scattering. Kinetics of inactivation can be resolved into two phases and at the same protein concentrations, the unfolding and aggregation rates are about one order of magnitude slower than the fast phase and approximately the same as the slow phase rate of the inactivation reaction between 35 and 60 degrees C. This is in general accord with the suggestion made previously that the active site of this enzyme is situated in a region more flexible than the molecule as a whole (Tsou, C.L. (1986) Trends Biochem. Sci. 11, 427-429). The inactivated enzyme cannot be reactivated by cooling and standing at 4 degrees C but can be over 80% reactivated by cooling and first standing in 3 M guanidine hydrochloride followed by diluting out the denaturant. PMID- 8518298 TI - Wide distribution of an enzyme that catalyzes the hydrolysis of cyclic ADP ribose. AB - Cyclic ADP-ribose (cADPR) is a metabolite of NAD+ that is as effective as inositol trisphosphate in mobilizing intracellular-Ca2+ stores. Its synthesizing enzyme, ADP-ribosyl cyclase, has been shown to be present in mammalian and invertebrate tissues. In this study we identify another widely-distributed enzyme that can hydrolyze cADPR to ADP-ribose. Incubation of cADPR with brain extracts resulted in progressive decrease in its Ca2+ mobilizing activity. The degradation of cADPR was catalyzed by a heat-labile protein factor in the brain extracts. Analysis by HPLC indicated a single degradation product was produced in equal molar quantity and that it has identical elution time as ADP-ribose. Proton NMR confirmed that the product was ADP-ribose. The degradation enzyme had a Michaelis constant of 0.16 mM and a broad pH maximum around neutrality. Centrifugation studies of the total brain extracts showed that the degradation activity was membrane-bound. Survey of tissues from various animals established that both the degradation and the synthesizing enzyme of cADPR were widely distributed from mammals to invertebrates. Since the degradation enzyme hydrolyzes an unique linkage between the adenine group and the terminal ribosyl moiety of cADPR, we propose to call it cyclic ADP-ribose hydrolase. PMID- 8518299 TI - Structural analysis of tissue inhibitor of metalloproteinases-1 (TIMP-1) by tryptic peptide mapping. AB - Tryptic digests of recombinant TIMP-1 have been resolved on reverse-phase HPLC and the major peaks identified by N-terminal sequencing. This procedure accounted for the entire molecule, except two short peptides of 2 and 4 amino acids in length. The peptide map was used to (i), characterize an insoluble 'core' peptide seen on digestion of TIMP-1 in non-reducing conditions; (ii), confirm the structure of delta 127-184TIMP-1, a recently described truncated form of the TIMP 1 molecule; (iii), identify exposed regions of the intact and truncated TIMP-1 molecules by measuring the rate of tryptic peptide release and (iv), locate sites of aberrant proteolysis seen when recombinant human TIMP-1 was purified at large scale. PMID- 8518300 TI - Fusion activity of an amphiphilic polypeptide having acidic amino acid residues: generation of fusion activity by alpha-helix formation and charge neutralization. AB - A sequential polypeptide, poly(Glu-Aib-Leu-Aib) (Aib represents 2-aminoisobutyric acid), was synthesized and the pH-dependence of fusogenic activity of the polypeptide was studied. The polypeptide was designed to take amphiphilic structure upon the formation of alpha-helix. Circular dichroism spectra of the polypeptide showed a negative Cotton effect with double minima, indicative of an alpha-helical conformation. The alpha-helix content was increased with lowering pH and/or increasing the ionic strength. It was found that the polypeptide induces remarkable leakage of calcein from egg-yolk phosphatidylcholine (EYPC) vesicles loaded in the inner aqueous phase with lowering pH and/or increasing ionic strength. The polypeptide caused fusion of EYPC liposomes and dipalmitoylphosphatidylcholine liposomes more strongly with decreasing pH. Moreover, two distinct increases of fusogenic activity of the polypeptide were observed near pH 6.0 and below pH 4.5. The former corresponds to the midpoint of pH-dependent change in helical content of the polypeptide and the latter the pKa of the gamma-carboxyl group of glutamic acid. These results indicate that elevation of the fusogenic activity of the polypeptide is related to the increase in two factors, alpha-helix content and hydrophobicity. PMID- 8518301 TI - Properties of elastase from Atlantic cod, a cold-adapted proteinase. AB - An intestinal elastase was purified from Atlantic cod (Gadus morhua) of apparent molecular mass 24.8 kDa as determined by SDS-PAGE and with isoelectric point above pI 9.3. Heat stability and stability towards acidic pH was reduced in the cod enzyme as compared with porcine intestinal elastase. N-terminal amino-acid sequence analysis of cod elastase showed considerable similarity with porcine elastase. The cod enzyme was less sensitive to phenylmethylsulfonyl fluoride inhibition than porcine elastase, but sensitivity towards other inhibitors was similar. Kinetic properties were examined using the substrate Suc-Ala-Ala-Ala-p nitroanilide and the cod enzyme was found to have more than 2-times turnover rate (kcat) as compared with the porcine enzyme, and slightly higher Km values. Thus, the catalytic efficiency (kcat/Km) of Atlantic cod elastase was about 2-times higher than observed with porcine elastase, which indicates an adaptive response towards the low temperature environmental in which the cod lives. Substrate specificity was studied by digestion of oxidized B-chain of insulin and by using synthetic substrates. Digestion was most rapid at the carbonyl side of alanine residues, but also occurred at valine and leucine residues. PMID- 8518302 TI - [The omitted x-ray examination--benefit and risk--a comparison]. AB - Today the risk of omission of an x-ray examination is often underestimated compared with the assumed stochastic - i.e. random - risk of radiation exposure associated with the x-ray examination. The benefit of the x-ray examination can be estimated by considering how it influences the diagnostic decision and the therapy. Three degrees of justification (indication) supply proof of different degrees of the proportion of benefit gained. It is evident that some of the x-ray examinations that are being performed, are unnecessary, whereas on the other hand even so-called routine x-ray examinations can yield a therapeutically relevant finding in some patients. A comparison of benefit and risk shows that the estimated benefit exceeds the assumed irradiation risk by several orders of magnitude. This is exemplified by examinations of the thorax and lumbar vertebral column. The guidelines issued by the German Federal Chamber of Physicians on quality assurance in x-ray diagnostics and CT result in a considerable reduction of patient doses. Advantage must be taken of the benefit of x-ray examinations performed with an extremely critical eye on the relevant indication and with minimised irradiation exposure. Omitting an indicated examination may endanger the patient to such an extent that major neglect of the irradiation risk is warranted. PMID- 8518303 TI - [Positron-emission tomography (PET)--a new diagnostic method. Physical and technical requirements]. AB - Technical and physical requirements and parameters of positron emission tomography are discussed. Scanners and cyclotrons are described and PET is compared with SPECT. PMID- 8518304 TI - [Detectability of pulmonary coin lesions: a comparative assessment of the image quality of a storage phosphor system and a conventional film screen system]. AB - The object of this study was to compare the prototype of a storage phosphor digital radiography system (Siemens) which allows postprocessing image data adjustment with the stored information, with an optimised conventional film system with respect of image quality and diagnostic accuracy. The test objects were pulmonary coin lesions as the search for primary or secondary lung tumours is one of the most frequent clinical requests and the detectability of coin lesions depends very much on their relative contrast against the surrounding area. In order to achieve reproducible results, an anthropomorphic lung phantom was used. Besides the conventional film radiograms the unprocessed digital radiograms and twelve series with variations of the processing parameters were evaluated. To achieve a homogeneous radiation image an anatomically shaped lead loaded acrylic glass compensation filter was used. With regard to the true positive demonstration of coin lesions there were no significant differences between the chosen film system and all digital radiograms. Image processing had no recognisable influence on the demonstration of the findings. Coin lesions of 3 mm diameter were detected only by chance; the detectability of lesions of 5 mm and 10 mm in diameter respectively depended mainly on their localisation. Lesions of 15 mm diameter were detected independent of their localisation. The results indicate that the storage phosphorus radiography system is already comparable to an optimised conventional film system concerning the conspicuity of coin lesions. If the image is homogenised by means of an anatomically shaped lead-loaded acrylic glass compensation filter, selective postprocessing adjustment of the digital radiograms for the evaluation of the mediastinum or the lung parenchyma is unnecessary. PMID- 8518305 TI - [Digital hilar tomography. A comparison with the conventional technique]. AB - The aim of the following study was to compare conventional hilar tomography and digital hilar tomography. 20 patients were examined both with conventional and digital hilar tomography using the same tomographic technique and the identical exposure dose. All patients underwent computed tomography of the chest as a golden standard. The digital technique, especially the edge-enhanced image version, showed superior image quality. ROC-analysis by 4 readers found equal diagnostic performance without any statistical difference. Digital hilar tomography shows a superior and constant image quality and lowers the rate of re exposure. Therefore, digital hilar tomography is the preferable method. PMID- 8518306 TI - [Visualization of the normal basilar artery and its branches using magnetic resonance angiography (MRA)]. AB - MRA (magnetic resonance angiography) is besides duplex sonography at present the only noninvasive method for vascular visualisation. The technical fundamentals and our initial experiences with this new technique of angiography in the visualisation of the basilar artery are presented in the following article. PMID- 8518307 TI - [The importance of imaging techniques in gallstone disease]. AB - The available surgical and non-surgical therapy options for treatment of gallstone disease are presented. Conventional cholecystectomy is regarded as standard therapy of symptomatic cholecystolithiasis. Other modes of therapy may be indicated under certain circumstances, depending on the results of imaging procedures. In this context conventional X-ray examination, oral and intravenous cholecystography, sonography, computed tomography, endoscopic retrograde cholangiography/cholecystography, and magnetic resonance imaging are discussed and their influence on therapeutic decisions is explained. PMID- 8518308 TI - [Bolus administration in spiral CT of the upper abdomen]. AB - In 60 patients the density increases in the abdominal aorta and pancreas were examined quantitatively the visualisation of the arterial liver blood flow qualitatively in a test volume by means of spiral CT and a feed or speed differentiation of 10 mm/s for three different contrast medium boli. It was shown that during the entire study over 24 seconds the boli with 100 ml contrast medium at injection speeds of 3 ml/s and 50 ml contrast medium at 1.5 ml/s resulted in a continual density increase of the abdominal aorta from 221 to 265 Hounsfield Units (HU) or 161-167 HU, respectively. For measuring the abdominal aorta the bolus of 50 ml contrast medium at 3 ml/s was less suitable than the boli of 100 ml contrast medium with 3 ml/s and 50 ml with 3 ml/s because of the rapid in density from 250 to 118 HE. The bolus of 50 ml contrast medium and 3 ml/s, on the other hand, with 54 HU enhancement of the pancreas was approximately equal to the larger amount of contrast medium of 100 ml contrast medium and 3 ml/s with 56 HU, whereas 50 ml contrast medium and 1.5 ml/s with 46 HU was inferior. While all boli could sufficiently enhance the extrahepatic section of the hepatic artery, the larger amount of contrast of 100 ml proved to be superior to the other boli in the visualization of central intrahepatic vascular branches. PMID- 8518309 TI - [Differential diagnostic problems in a polycystic, atypically calcified renal cell carcinoma]. AB - The renal cell carcinoma as the most common malignant renal tumour in adults may produce diagnostic difficulties if it follows atypical patterns. In the case of a polycystic renal tumour this problem is discussed; the high sensitivity of CT and MRT in detecting even small areas of solid tumour is shown. PMID- 8518310 TI - [Angiolipoma of the kidney as a secondary tumor in a patient with a soft tissue sarcoma of the upper arm]. AB - The case of a 51-year-old male presenting with a tumour of the left kidney is reviewed. In respect of an operated tissue sarcoma of the right humerus 6 months ago, radiological findings suggested a benign lesion, but could not exclude a metastasis of the sarcoma. Histological diagnosis revealed an angiomyolipoma of the kidney. PMID- 8518311 TI - [Nuclear spin tomography of the hands of a patient with Maffucci's syndrome]. AB - Maffucci's syndrome is associated with tumours of the soft tissues and enchondromas. The hands are involved in the majority of patients. Magnetic resonance imaging (MRI) enables the demonstration of the soft tissue structures and the bone marrow of the hand. The hands of 19-year old patient with Maffucci's syndrome were examined via MRI and the results were compared with radiographs, angiograms and skeletal scintiscans of the hands. MR imaging shows a more expansive infestation with enchondromas than the radiographs. Haemangiomas were also visualised. PMID- 8518312 TI - [Galeazzi's fracture in the x-ray picture]. AB - Galeazzi's fracture represents the rather rare association of a fracture of the radial shaft with disruption of the distal radio-ulnar joint (13). The assessment of 19 galeazzi's fractures revealed the typical displacement of the distal radial fragment with a concomitant contraction in 7 and a lateral dislocation to the ulnar and/or volar side in 7 cases. The characteristic dorsal and/or lateral dislocation of the ulna following the disruption of the distal radio-ulnar joint was seen in 16 patients. Besides this dislocation additional radiographic signs of the rupture of the capsule and ligaments were a widening of the joint space of the distal radio-ulnar articulation shown on the ap-projection in 10, a pathological shortening of the radius or ulnae in 7 and the avulsion of the ulnar styloid process in 10 patients. PMID- 8518313 TI - [The intravertebral vacuum phenomenon. A rare finding in vertebral compressions]. AB - In the context of osteoporotic vertebral compression fractures the formation of an intravertebral vacuum phenomenon is a very rare but characteristic feature. Ischaemic osteonecrosis has been discussed as a probable cause of the disease. In most cases the vertebrae Th12, L1 or L3 are affected. Just over 60 case reports have as yet been published in international literature. Our two case reports fit well into the existing picture of the intravertebral vacuum phenomenon. PMID- 8518314 TI - [MRI characteristics of the Sneddon syndrome]. AB - The report describes the MRI findings in a female patient with an established long course of a Sneddon's syndrome. Multiple ischaemic cerebral infarcts of a mainly macroangiopathic pattern are typical. In the beginning the corresponding clinical deficiencies often show a considerable regression. PMID- 8518315 TI - The development of a strategy for the implementation of automation in a bioanalytical laboratory. AB - Laboratory automation is equipment, instrumentation, software and techniques that are classified into four groups: instrument automation; communications; data to information conversion; and information management. This new definition is necessary to understand the role that automation can play in achieving the aims and objectives of a laboratory within its organization. To undertake automation projects effectively, a laboratory automation strategy is outlined which requires an intimate knowledge of an organization and the target environment to implement individual automation projects. PMID- 8518316 TI - The study of the differential pulse voltammetric behaviour of ergot alkaloids and their determination by DC amperometric detection in a FIA system. AB - The ergot alkaloids possess strong pharmacological effects and are important drugs with widespread clinical uses. The ergot alkaloid preparations manufactured by Gedeon Richter Chemical Works Ltd have a very low active substance content (e.g. 1.0 mg in each Secadol (0.4 g) coated tablet); therefore a sensitive method of determination must be used. Because of this constraint the differential pulse voltammetric behaviour of ergot alkaloids was studied in respect of the effects of pH and composition of media and an automated FIA system with amperometric detection has been used to develop a selective and sensitive method for the routine quantitative assay of these alkaloids. A short summary is given of the experimental evidence to substantiate the stoichiometric equation proposed for the electrochemical oxidation of the lysergic acid type of ergot alkaloids, the mechanism may be generally applicable for compounds having the ergoloid skeleton. In the course of the work it was concluded that a simple DC amperometric method of detection in a FIA system could be applied to determine the content of ergot alkaloids of different pharmaceutical preparations. A suitable method designed to meet current analytical requirements has been developed and validated. PMID- 8518317 TI - Capillary zone electrophoresis and micellar electrokinetic capillary chromatography of some non-steroidal antiinflammatory drugs (NSAIDs). AB - The possibilities of capillary electrophoresis (CE) and micellar electrokinetic capillary chromatography (MEKC) were investigated for the qualitative analysis of some non-steroidal antiinflammatory drugs. In CE the influence of the pH of the buffer and its ionic strength were investigated for a test mixture of six compounds. Also the influence of organic modifiers was studied. The best conditions were applied to the separation of 15 drugs. In MEKC the influence of the concentration of SDS in buffers with pH ranges of 8.0-9.0 was investigated. The influence of an organic modifier, namely acetonitrile was discussed, whereby an interesting phenomenon of change in retention behaviour was noted. A combination of CE and MEKC allows the separation of the 15 above-mentioned compounds and forms an interesting alternative to HPLC. PMID- 8518318 TI - A study of the electrochemical oxidation of Navelbine. AB - The search for drugs with cytostatic activity and with better pharmacokinetic features led to the synthesis of Navelbine (5'-noranhydrovinblastine) which is a structural modification of antitumour Vinca alkaloids. The new drug Navelbine has high liposolubility, a lower toxicity and increased antitumour activity. The electrochemical oxidation of Navelbine was studied over a wide pH range (1.2 12.8) at a glassy carbon disc electrode in buffered aqueous media using differential pulse and cyclic voltammetry. The anodic oxidation mechanism is a very complex, pH dependent, multistep electron transfer process with coupled homogeneous chemical reactions. PMID- 8518319 TI - Coulometric determination of some antiasthmatics. AB - A simple and rapid method for the assay of microquantities of fenoterol hydrobromide, orciprenaline sulphate and terbutaline sulphate in pure state and various pharmaceutical formulations, is presented. The method is based on the coulometric titration of the investigated compounds with electrogenerated chlorine in the presence of methyl orange as indicator. The method requires a simple apparatus and gives accurate and reproducible results. PMID- 8518320 TI - Simultaneous isolation of Rutin and Esculin from plant material and drugs using solid-phase extraction. AB - Simultaneous isolation of Rutin and Esculin from pharmaceutical materials (plant- Flos hippocastani and drugs--Venescin, Venacorn) using solid-phase extraction (SPE) have been made. For this investigation the Bakerbond SPE columns with different unpolar and polar chemically bonded phases were used. On the basis of isolation investigation the influence of SPE packing materials on the selectivity change and recovery of both extracted substances were studied. PMID- 8518321 TI - Determination of ivermectin in bovine plasma by column-switching LC using on-line solid-phase extraction and trace enrichment. AB - Ivermectin is a potent avermectin anthelmintic, derived from the soil organism Streptomyces avermitilis. Because of its potency, it is administered in very low doses (200 micrograms kg-1), giving rise to plasma levels in the ppb region, and hence sensitive methods are required for its determination in biological samples. A method is described for the determination of ivermectin in bovine plasma, based on a commercially available C18 column employing a mobile phase composed of acetonitrile-water-isopropanol (40:40:35, v/v/v). Extraction from plasma is carried out on-line using coupled-column technology; switching between the extraction and analytical columns is achieved using a six-port column-switching valve. The method is linear over the range 2-100 ng ml-1 (r = 0.9994) and has a limit of detection of 0.8 ng ml-1 (signal-to-noise ratio = 3). Reproducibility of the method, expressed as the overall mean relative standard deviation, is 6.7% (intra-assay) and 3.8% (inter-assay). The mean recovery of the drug from plasma is 76.4%. The method is simple and economical in its execution and is sufficiently reproducible to obviate the need for an internal standard. PMID- 8518322 TI - Determination of enantiomers of bupivacaine in serum using an on-line coupled three column liquid chromatographic system. AB - An on-line coupled HPLC system is described for the determination of the enantiomers of bupivacaine in serum. The method involves three steps: (i) pre concentration and clean-up; (ii) the determination of the racemates on a reversed phase column; and (iii) the separation of the racemates, heart-cut from the reversed-phase column, on an alpha-glycoprotein column. The method is suitable to determine the enantiomers in serum down to 0.1 micrograms ml-1 and can be fully automated. The bupivacaine time course of patients will be shown. PMID- 8518323 TI - LC studies on the potential interaction of paraben preservatives with sorbitol and glycerol. AB - Pharmaceutical formulations often contain one or more paraben preservatives in conjunction with a polyol such as sorbitol or glycerol. In one of these experimental formulations a number of unknown polar peaks have been detected near the solvent front by reversed-phase LC. These degradation products were not attributable to the active drug component or a hydrolysis product. The possibility of an interaction between the polyols and paraben preservatives has been explored using a three-variable, two-level, factorial design to determine the relative significance of the factors involved in the formation of these unknown peaks. The factors examined were pH, temperature and the ratio of polyol to paraben. This study has shown that pH and temperature are key factors affecting the formation of these unknown peaks. On the basis of these results suitable conditions can be suggested for minimizing the production of these unknown peaks. It seems clear that a number of pharmaceutical formulations containing a polyol and a paraben would present potential problems for assay validation on storage owing to the formation of these degradation products, particularly if the drug component is polar and elutes near the solvent front. PMID- 8518324 TI - Thin-layer reversed-phase ion-pair chromatography of some sulphonamides. AB - The retention behaviour of 15 sulphonamides was investigated by thin-layer reversed-phase ion-pair chromatography (RP-IPC). Optimization of the retention and selectivity of these compounds was carried out by changing the pH, the concentration of the ion-pairing counter-ion and the concentration of the organic solvent in the aqueous mobile phase. The effects of various cationic and anionic pairing reagents in the mobile phase and the stationary phase were investigated. The use of stepwise gradient elution improved the spot shape and the selectivity of the separation. PMID- 8518325 TI - Spectrophotometric determination of molsidomine in pharmaceutical formulations using bromocresol green. PMID- 8518326 TI - Metabolism of the new MAO-A inhibitor brofaromine in poor and extensive metabolizers of debrisoquine. PMID- 8518327 TI - Reversed-phase ion-pair liquid chromatographic method for determining the impurities of furosemide. PMID- 8518328 TI - Liquid chromatographic resolution of the enantiomers of psychotropic drug levomepromazine (methotrimeprazine) with beta-cyclodextrin-bonded chiral stationary phase. PMID- 8518329 TI - Circulatory effects caused by intra-arterial infusion of AMP, ADP and ATP in the canine facial and nasal vascular beds. AB - The effects of the intra-arterial infusion of ATP, ADP and AMP into the internal maxillary artery (IMA), which provides the blood supply to the nasal and forehead regions of the dog, were analyzed. Total blood flow and perfusion pressure measurements in the IMA after administration of each adenyl compound indicated dose-dependent and active vasodilatory responses that were restricted to the ipsilateral vessels. The rank order of potency was ADP > or = ATP > AMP. In order to determine the microcirculatory effects caused by ADP, the tracer microsphere technique combined with absolute blood flow measurement was used. Intra-arterial infusion of ADP in the range 1-200 nmol/min produced elevations in the IMA flow on the stimulated side that ranged between 11 and 74%. The responses to low doses of ADP were mainly confined to the capillaries (CAP), whereas the arteriovenous anastomoses too were sensitive to high doses. The relative contributions of the anatomically and functionally different compartments of the forehead and nose to ADP-produced relaxations of the CAP were dependent upon their location. The CAP flows in the tissues which play a crucial role in conditioning the inspired air increased significantly, while the compartments of the furred surfaces were less sensitive to ADP. The results suggest that, since ATP, ADP and AMP are effective vasodilatory agents in all the regions examined, purines could have a regulatory or modulatory role in the complex vascular regulation of the nasal and forehead regions. PMID- 8518330 TI - Mechanisms of histamine-induced coronary vasodilatation: H1-receptor-mediated release of endothelium-derived nitric oxide. AB - Although the content of histamine in myocardial tissue is high, its contribution to the regulation of coronary blood flow has not been clearly defined. The aim of the present study was to investigate whether or not nitric oxide (NO), an important modulator of coronary vascular tone, is involved in histamine-induced coronary vasomotion and to characterize which histaminergic receptor subtype mediates this process. Isolated, constant-flow-perfused guinea pig hearts were challenged with histamine, the H1-receptor agonist pyridylethylamine (PYR) and the H2-receptor agonist dimaprit (DIM). Apart from coronary perfusion pressure (CPP), left ventricular pressure (LVP) and the development of contractile force (dp/dt), the release of NO and cyclic GMP (cGMP) were continuously measured. Histamine and DIM induced concentration dependently a coronary vasodilatation with an almost 50% decrease in CPP paralleled by an enhancement of LVP and dp/dt by more than 80%. PYR selectively reduced CPP by 47% without affecting LVP and dp/dt. Histamine- and PYR-induced coronary vasodilatation were paralleled by a more-than-twofold increase in basal cGMP release from isolated hearts, whereas DIM exerted no effects on cGMP release. Oxyhemoglobin (4 microM), an effective scavenger of NO, shifted the concentration-response curve for histamine- and PYR induced changes in CPP significantly to the right and in parallel inhibited the increase in cGMP release. Histamine and PYR rapidly (within 2 s) decreased CPP, while the onset of DIM-induced coronary vasodilatation followed changes in LVP with a lag period of 10 s. Histamine increased basal NO release concentration dependently by a maximum of 351 +/- 21 pmol/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518331 TI - Endothelin receptor regulation by endothelin synthesis in vascular smooth muscle cells: effects of dexamethasone and phosphoramidon. AB - One of the major biological effects of the endothelium-derived peptide endothelin 1 (ET-1) is its receptor-mediated constrictive action on vascular smooth muscle. In this study, we have examined the effects on the ET-1 pathway of 18 h exposure at 37 degrees C of cultured rat aortic smooth muscle cells to dexamethasone (DEX) and phosphoramidon. ET-1 synthesis was evaluated by radioimmunoassay, ET-1 binding characteristics were determined with [125I]iodo-ET-1, and ET-1-induced intracellular calcium mobilization was measured using fura-2-loaded cells. DEX (100 nM) led to a 2- to 3-fold-increase of ET-1 production, it down-regulated ET 1 receptors and reduced ET-1-stimulated calcium mobilization by 70%. In contrast, phosphoramidon (100 microM) inhibited ET-1 production by 60%, up-regulated ET-1 receptors and potentiated ET-1-induced calcium mobilization by 75%. These results indicate that the regulatory effects of DEX and phosphoramidon on ET-1 receptors are mediated via ET-1 production by the cells. This suggests an autocrine control of ET-1 receptors by endogenous ET-1 synthesis in vascular smooth muscle cells. PMID- 8518332 TI - Pulmonary artery endothelial dysfunction following ischemia and reperfusion of the rabbit lung. AB - We studied endothelial dysfunction of the rabbit pulmonary artery following in vivo ischemia and reperfusion of the lung, and also investigated the mechanisms of endothelium-dependent relaxation in these arteries. Intrapulmonary arteries were isolated from rabbits subjected to ischemia and reperfusion of one lung. Percent relaxation values of sham-operated (i.e. nonischemic) pulmonary arteries to endothelium-dependent vasodilators acetylcholine (ACh) and A23187 were 72 +/- 4 and 65 +/- 4%, respectively, while relaxation to the endothelium-independent dilator NaNO2 was 97 +/- 1%. The relaxation of control artery rings to ACh and A23187 were significantly decreased to 2 +/- 1 and 5 +/- 4%, respectively, following addition of N omega-nitro-L-arginine methyl ester, while relaxation following treatment with indomethacin or glybenclamide remained normal. Relaxation to NaNO2 was not altered by pretreatment with any of the above compounds. Thus, pulmonary artery relaxation to the endothelium-dependent dilators ACh and A23187 appears to be mediated by the release of EDRF. Endothelium-dependent relaxation of pulmonary arteries from lungs exposed to 90 min of ischemia and 30 min of reperfusion remained essentially normal, while 90 min of ischemia followed by 60 min of reperfusion resulted in a significant decrease in endothelium-dependent relaxation to A23187 to 37 +/- 7% (p < 0.05), whereas the response to ACh was reduced only to 57 +/- 3% (not significant). 90 min of ischemia followed by 90 min of reperfusion resulted in significant attenuation of endothelium-dependent relaxation to both ACh (36 +/- 4%) and A23187 (33 +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518333 TI - Canine jugular vein endothelial cell monolayers in vitro: vasomediator-activated diffusive albumin pathway. AB - Cultured canine jugular vein endothelial cells were seeded on polycarbonate filters to create an in vitro permeability assay. The calculated diffusive permeability coefficient for FITC-BSA across untreated monolayers was 1.1 +/- 0.4 x 10(-6) cm/s. After 15-min incubations with either histamine or bradykinin, the resistance to albumin flux across the monolayers was reduced significantly. Diffusive albumin permeability coefficients were 3.4 +/- 1.8 x 10(-6) and 4.1 +/- 2.0 x 10(-6) cm/s, respectively. Ultrastructural morphometric analyses of the endothelial cell monolayers served to define uniform dimensions of intercellular clefts and similar plasmalemmal vesicle densities in the untreated and the vasomediator-activated monolayers. These results are consistent with the interpretation that the vasomediator-activated pathway across the venous endothelial monolayers is not dependent on sustained intercellular gap formation or sustained expansion of the plasmalemmal vesicle population for the 15-min observation periods. Whether the increased albumin flux is dependent on transient gap formation or on physical changes within the venous endothelial cell glycocalyx remains to be tested. PMID- 8518335 TI - [Fallacies, realities and truths in osteoporosis]. PMID- 8518334 TI - Heparin increased cell membrane-associated heparan sulfate proteoglycan in balloon-injured rat carotid artery. AB - The effect of heparin on the amount of membrane-associated heparan sulfate proteoglycan (HSPG) was examined biochemically in balloon-injured rat carotid arteries. Heparin (Choay 1772) was administered at the rate of 1 mg/kg/h.i.v. by an osmotic infusion pump for 10 days. Arterial tissues were incubated ex vivo with Na2(35)SO4 and 3H-glucosamine for 6 or 24 h. The arteries from heparin treated rats were also incubated with heparin (100 micrograms/ml) during the radiolabeling. Membrane-associated proteoglycans were extracted with 4 M guanidine-HCl and isolated by a series of chromatographic steps using Sephadex G 50, DEAE-Sephacel and Octyl-Sepharose CL-4B. Membrane-associated proteoglycans were eluted with 0.8% Triton X-100 from Octyl-Sepharose columns. Heparin treatment significantly increased membrane-associated HSPG by 64% in the arteries incubated for 24 h, while heparin hardly increased the HSPG in 6 h incubated arteries. Since the 24-hour data seem to reflect a combination of biosynthesis and degradation of proteoglycans while the 6-hour data primarily reflect biosynthesis, these results suggest that inhibition of degradation of membrane associated HSPG is involved in the mechanism of heparin action. This speculation is supported by the observation that membrane-associated HSPG was elevated in balloon-injured arteries by treatment with protease inhibitors. PMID- 8518336 TI - [Significance of angina in patients with aortic valvulopathy]. AB - We have analyzed coronary arteriographies of 170 patients, 120 with isolated aortic stenosis and 50 with isolated aortic failure. Patients with stenosis showed higher frequency of angina (73% versus 54%, p = 0.0223). No significant differences were observed with respect to the incidence of the coronary artery disease (26.7% versus 31.8%, p = 0.18). The presence of angina was significantly more specific in aortic failure (specificity 52.4% versus 31.8% in aortic stenosis, p = 0.039). Among the patients with less than 56 years of age, the probability of developing coronary artery disease in absence of angina was 6.3% (1 out of 16), the confidence interval ranging from 1.5% to 30.2%. Our results do not support any modification of the conventional criteria for conducting coronary arteriographies in patients with aortic valvulopathy. PMID- 8518337 TI - [Double blind comparative randomized study of the efficacy of celiprolol versus amiloride-hydrochlorothiazide in mild to moderate AHT]. AB - We tried to assess the antihypertensive effectivity of a betablocker, celiprolol, in the control of mild to moderate essential arterial hypertension. A double blind randomized comparative study was conducted between celiprolol and amiloride hydrochlorothiazide in 40 patients with mild to moderate essential hypertension. Both drugs were effective in the therapeutical control of hypertension, although reductions in systolic blood pressure were more significant among the celiprolol group, being the percentage of patients with reduction of diastolic blood pressure below 90 mmHg., 89.5% in the celiprolol group and 82.4% in the amiloride group. The average dose of celiprolol used was 200 mg/day, with few mide effects. PMID- 8518338 TI - [Contribution of transcervical mediastinoscopy and anterior mediastinostomy to the diagnosis of mediastinal lymphomas]. AB - The aim of this study has been to assess the profitability of mediastinal explorations (transcervical mediastinoscopy and anterior mediastinostomy) in the diagnosis of mediastinal lymphomas within a short-stay surgery programme. Out of 129 mediastinal explorations conducted within a period of six years, 63 were programmed as short-stay surgery, 24 of which were due to mediastinal lymphomas. Fourteen patients were discharged from the hospital within the first twelve hours and ten patients, after 24 hours. RESULTS: There were 11 cases of Hodgkin's lymphomas and 13 non-Hodgkin's lymphomas. No immediate complications were developed by the patients, with just two minor complications which did not delay hospital discharge. CONCLUSIONS: Mediastinal explorations (transcervical mediastinoscospy and anterior mediastinostomy) can be planned as short-stay surgery without any risks if they are conducted by groups with experience in these surgical techniques and provided with an adequate care infrastructure. This allows a more rationale usage of hospital resources without reducing the quality of care. PMID- 8518339 TI - [Pulmonary cryptosporidiosis and AIDS. Presentation of a case and review of the literature]. AB - Pulmonary cryptosporidiasis is a rare disease. However, following the advent of the acquired immunodeficiency syndrome (AIDS), this rare pathology infection by Cryptosporidium and we conduct a literature review. The Cryptosporidium can be detected with the routine technique used for the identification of mycobacterias in sputum: Zichl-Neelsen, auramine O, Kinyoun, etc. The most frequent sympthomatology includes chronic cough (91%), fever (59%) and dyspnea (64%). In 78% of cases, several respiratory infectious agents coexist, mainly P. carinii (47%) and Cytomegalovirus (41%). In 76% of cases, the infection is followed by diarrhea, detecting Cryptosporidium in the feces of 80% of these patients. The most frequent cause of death is respiratory failure. The radiologic evidences are not specific. The OKT4+/OKT8+ ratio has an average value of 0.3 (0.05-0.9). There is not any treatment truly effective. PMID- 8518340 TI - [Kartagener's syndrome with normal ciliary ultrastructure]. AB - We present a case of a man with Kartagener's syndrome (KS) (situs inversus, sinusitis and bronchiectasias) and with clinical signs of respiratory infection. An electronic microscopy study was conducted, showing a normal bronchial cilium. Although, traditionally, KS has been associated to ultrastructural abnormalities of the cilium, some cases similar to ours have been described, suggesting the presence of functional ciliary disorders in absence of ultrastructural defects. PMID- 8518341 TI - [Pulmonary lymphangioleiomyomatosis. A disease which may have a benign progression]. AB - Pulmonary lymphangioleiomyomatosis (PLLM) is characterized by a benign proliferation of the smooth muscle around lymphatics, venulas and bronchiolus. It is usually fatal within 1 to 9 years. We present a case which remained with scarce symptoms despite receiving no treatment after at least 9 years of evolution of the disease. We highlight the clinical manifestations of the disease and the relevance of pulmonary biopsia with thoracotomy in order to establish the diagnosis. PMID- 8518342 TI - [Idiopathic myelofibrosis. A disease with multisystemic manifestations]. PMID- 8518343 TI - [Microproteinuria]. AB - The microproteinuria is an increase in the urinary excretion of proteins (non selective, mainly albumine) undetectable with the routine laboratory tests. The detection of microproteinuria has a relevant role in those diseases causing renal damage and with mechanisms involving the extravasation of proteins at the level of the glomerular ball. Such detection allows a therapeutical action and the evaluation of the results. If the disease is multisystemic, it would also be correlated with lesions in other affected organs. PMID- 8518344 TI - [Poor promotional practices in pharmaceutical communication: the anti- medical visit, International experience]. AB - We start with a short introduction about the concept of "bad promotional practices" within the Pharmaceutical Industry's (PHI) communication, giving rise to the birth of so-called "un-representatives" (un'rep). Taking the self-control model from the "Association of the British Pharmaceutical Industry" (ABPI), based upon the "code of practice" as a paradigma, we comment about those who notify presumed code's breaches besides the assessment process and penalties that are usually imposed. We also considered the possibility that sometimes the physician instead of being a prosecutor is accused, by the PHI, of supposed "Medical Deonthological Code's" Infringement. The several modalities of malpraxis during the un-rep visit are classified into four categories: product un-information; unloyal competition; echonomical temptations addressed toward physicians; and disregarding stablished visit planning. We devote most of the text to exemplarize five common and very well documented situations; promotion of non-registered indications; influence of prescriptions through prebends to doctors; doubtful payments to compensate clinical trials and drug surveillance studies; the use of exagerated claims; and the abuse of the qualification "drug of choice". We end with a self-critism, from the phi's outlook on the prudence that a "good pharmaceutical communicator" must respect. As an excellent model of wisdom, we propose doctors, Because they follow the classical good-sense picture that illustrates the process of adoption of a new drug. We emphasize the fact that product over-estimation, creating false expectatives, is--together with the lak of informative liability--one of major reasons for a drug innovation to fail. PMID- 8518345 TI - [Bronchial carcinoids: histologic diagnosis]. PMID- 8518347 TI - [Paroxysmal supraventricular tachycardia as relevant manifestation of hypoglycemia]. PMID- 8518346 TI - [Steroid therapy of non-specific aphthous ulcers in patients with HIV infection]. PMID- 8518348 TI - [The education of the specialist in family and community medicine. Times of change, yes, but.... The Working Group on the Law of Specialties of the Spanish Society of Family and Community Medicine]. PMID- 8518349 TI - [Family physicians: the Spanish response to the European Community]. PMID- 8518350 TI - [An analysis of the level of accuracy of the official diagnosis of temporary work incapacity]. AB - OBJECTIVE: To assess the precision of the Sickness Certificate (SC) issued for Temporary Unfitness for Work (TUW). To measure the percentage of TUW where the diagnoses in the medical records and in the TUW Sickness Certificate do not coincide. To seek objective criteria to determine TUW. DESIGN: A descriptive, prospective and observational study. SETTING: Health Centre in an urban area in Vitoria. PATIENTS AND OTHERS PARTICIPANTS: All the sickness occasioning time off work between May and July, 1991, recorded at the above Health Centre: a sample of 224 TUW. MEASUREMENTS AND MAIN RESULTS: In 11.6% of the TUW the diagnoses did not coincide. The main reasons for the lack of correspondence were: initial ignorance of the diagnosis (34.6%); confidentiality before a third party (25.9%); pretense (14.8%). There was a notable difference between the psychological diagnoses (12) and those found in the official certificate 3 for TUW (p = 0.032). The most common diagnostic group was the locomotive one (29%). CONCLUSIONS: There is considerable inexactness in the diagnoses on the official TUW certificate. A lot of time off for psychological reasons is covered up by organic complaints. The locomotive group of complaints is the most commonly found one. We propose that the CIAP classification should be adopted to standardise diagnoses in this area. PMID- 8518351 TI - [The prevalence of mental illness in primary care and its relation to the degree of consultation frequency]. AB - OBJECTIVE: To establish the prevalence of psychic malaise within the population that consults the general medical clinic of our health center and the relationship between that prevalence and the frequency of consultation. DESIGN: Transversal descriptive study applying the GHQ test (28 items) to a sample obtained by mathematical sampling, using a questionnaire to collect sociodemographic data. SITE. The Health Center Segovia II (La Albuera) during November and December 1991. PATIENTS OR OTHER PARTICIPANTS: 360 patients over the age of fifteen were selected; 252 answered the test. MAIN MEASUREMENTS AND RESULTS: Considering the GHQ test as positive when score seven or more, a prevalence of psychic malaise of 33% was obtained. We found a statistically significant relationship between positive GHQ test and the frequency of consultation (p < 0.001) and female gender (p < 0.01). No statistically significant relationship was found between psychic malaise and the following variables: age, marital status, educational level and occupation. CONCLUSIONS: There is a high prevalence of psychic malaise within the population attending our general practice which can produce an increase in the demand. A biopsychosocial approach to all patients, with the aim of identifying that kind of problem and approaching it adequately, could reduce the use of health resources. PMID- 8518352 TI - [Factors associated with the prevalence of psychiatric morbidity in a health area]. AB - OBJECTIVE: To determine the incidence of psychiatric morbidity (PM) in the area, and the associated demographic and socio-economic factors. DESIGN: Observational non-longitudinal study. SETTING: The population of a Basic Health Area. PARTICIPANTS: Simple random sample of persons over 15 years old, selected from municipal census lists, accurate at 00.4. Initial sample: 697 cases. Excluded: deceased (11) changed address (112) serious mental incapacity (7) and refusal to take part (64). Final sample: 503 cases. MEASUREMENTS AND MAIN RESULTS: Answering of the General Health Questionnaire of 28 items (GHQ-28) and a questionnaire with study variables, between October 1990 and November 1991. 99 cases answered by post, and 404 via home visit. A GHQ-28 score greater or equal to 7 was considered positive. The incidence of GHQ-28 positive values in the population was found to be 0.35 (IC-0.31-0.39) and that of PM was found to be 0.38 (IC: 0.31-0.44). A link was observed with educational level (OR = 2.0277; p = 0.0174) and with sex (OR = 1.76 40; p = 0.172). There were no differences between those who answered by post or at home (p = 0.21) nor between those answering at different times of the year (p = 0.78). CONCLUSIONS: There was a high incidence of PM in persons older than 15 in our health area. This incidence is associated in a significant way with level of education (higher amongst lower levels) and with sex (higher amongst women). These factors can be considered as risk markers which can help us to detect sufferers from this type of illness. PMID- 8518354 TI - [A serum cholesterol study in a consulting population and its implications in clinical practice]. AB - OBJECTIVE: To investigate serious cholesterol levels in the population seeking medical attention, utilising HOTH (How Often That High) graphs, and to look at implications these results have for recording of cholesterol incidence. DESIGN: This was a non-longitudinal, retrospective, observational study. SETTING: Carried out at the general practice level, in the Valdefierro Basic Health Area (Zaragoza Province). PATIENTS: 742 subjects aged between 18 and 65 years with no previous history of dyslipemia. MEASUREMENTS AND MAIN RESULTS: After obtaining the figures on cholesterolemia, the HOTH graph was drawn from which, for a given cholesterol value, the percentage of the population with a given value can be seen. The mean cholesterol value was 201 mg/dl. A total of 54% of male subjects and 40% of female subjects were situated above the threshold figure of 200 mg/dl. Furthermore, 15% of male subjects and 10% of female subjects were situated above 250 mg/dl. CONCLUSIONS: The application of recording procedures for cholesterol, based on a globally discriminatory score, reveals a startling number of patients who need tests and treatment. We suggest a strategy based on the different levels according to age, sex, bloodstream cholesterol level, and the existence or otherwise of other cardiovascular risk factors. Lastly, we would mention the usefulness of the HOTH graphs in improving our knowledge of the cholesterol levels in a population. PMID- 8518353 TI - [A clinical trial on the efficacy of an alternative diet in obese patients]. AB - OBJECTIVE: To evaluate the effectiveness of a diet based on dietary advice in treating obesity. DESIGN: Random clinical investigation of two groups of obese people. SETTING: Two health centres in the city of Huelva. MEASUREMENTS AND MAIN RESULTS: We randomly assigned two types of diet, one consisting of dietary advice (A) and the other consisting of low calorie daily menus (B). These were followed for a period of 2 months. At the end of the period we administered a questionnaire on the difficulties in adhering to the diet. 88.4% of those on diet A lost weight, compared with 55.5% of those on diet B (p < 0.025). There were mean decreases in cholesterol and triglyceride levels with diet A of 12.37 +/- 12 and 22.1 +/- 18 mg/dl respectively. In the case of diet B, there were increases of these levels of 8.4 +/- 13 and 2.09 +/- 14 mg/dl respectively (p < 0.05). Of those who followed diet A, 16.7% said they experienced difficulty in keeping to it, while 45.4% of those on diet B said they experienced such difficulty (p < 0.025). Altogether, 29.16% of those who followed diet B (p < 0.025). CONCLUSIONS: With the diet based on nutritional advice a larger number of the subjects lost weight, felt less hungry hunger; this diet is easier to keep to, and produces a significant decrease in cholesterol and triglyceride levels. PMID- 8518355 TI - [An evaluation of dietetic treatment in juvenile hypercholesterolemia]. AB - OBJECTIVE: To evaluate compliance with dietetic treatment and its influence on levels of cholesterol and lipoproteins in hypercholesterolaemia in young children, over a period of two years. DESIGN: A descriptive longitudinal study. SETTING: Two paediatric clinics at the "Soria Norte" Health Centre. PATIENTS: 47 patients between 3 and 10 years old, with overall cholesterol levels > 185 mg/dl and C-LDL > 110 mg/dl. MEASUREMENTS AND MAIN RESULTS: 51% of the children correctly followed the dietetic advice given and at the 6 months follow-up showed an overall decrease in cholesterol and C-LDL. This decrease was less significant at a year from the start of the treatment. CONCLUSIONS: Diet is an efficacious treatment of hypercholesterolaemia in children. However, it is difficult to maintain over a long period. PMID- 8518356 TI - [Health problems detected in check-ups for the healthy child]. AB - OBJECTIVE: To assess the results of check-ups carried out on children when putting into practice the Programme for Healthy Children and various screenings. DESIGN: Crossover, descriptive study of the check-ups of healthy children carried out over a year (January to December, 1991). SETTING: Primary Care: the Pediatric Clinics of Soria Norte Health Centre, Soria. PATIENTS: All the children who had one or more check-ups during the study period. MEASUREMENTS AND MAIN RESULTS: The check-ups identified 0.78 problems per child. The greatest number of problems were found in the 15 day check-up, due to perinatal pathologies, followed by those at ages 3 and 6. The number of problems/number of check-ups relationship is 0.79 in children under 2 and 1.42 in those over 2. The problems occurring most often correspond to groups XV1, X1V and X11 (WONCA CIPSAP 11 Code). Groups V and V1 problems occurred most often at the ages when specific screenings were carried out. CONCLUSIONS: A high percentage of problems are found when checking healthy children, although many of them have very little clinical implication. The introduction of screening procedures at these check-ups assists the early identification of illnesses among this sector of the population. PMID- 8518357 TI - [Geographic isolation in the geriatric population of a rural town]. AB - OBJECTIVE: To estimate the prevalence and characteristics of geographic isolation in the elder people from Alora (Malaga). DESIGN: A transversal observational study. SETTING: Town of Alora. PATIENTS OR OTHER PARTICIPANTS: Elder people of both sexes, who lives habitually in Alora and born in 1927 or before. Home interview in a 153 individuals random sample proceeding from actual census during june to september 1992. MEASUREMENTS AND MAIN RESULTS: We found 25 individuals with the isolation conditions being the 16.34% (IC 95%: 10.48-22.20). In the 24% of them (IC 95%: 11.5-43.4) we found dependence of other person for two and more basic functions in the current life. Half of them this deficits are cover by the couple, the rest depends on their sons. We didn't found significative differences in none variables with the urban group. CONCLUSIONS: The geographic isolation affect to an important proportion of elder people in rural areas and must be used in the designs of care elderly programs. PMID- 8518358 TI - [The diagnosis of chronic hepatopathies in primary care: autoimmune chronic active hepatitis type 1]. PMID- 8518359 TI - [Estrogens and propranolol in the treatment of chronic iron-deficiency anemia due to gastric vascular malformations]. PMID- 8518360 TI - [The critical record: the registry system in consultation on demand]. PMID- 8518361 TI - [An analysis of the clinical decisions in primary care]. PMID- 8518362 TI - [Chronic pathologies in the elderly]. PMID- 8518363 TI - [An outbreak of acute respiratory infection in a public school of a rural town]. PMID- 8518364 TI - Human bifunctional antibody generated by heterologous association of heavy and light chains. AB - Hybrid antibodies, including bifunctional antibody, were obtained by fusing two different drug-resistant clones of human hybridomas HB4C5 and SU-1. One hybridoma, producing human IgM-class monoclonal antibody reactive to porcine carboxypeptidase A (Cpase), was a 6-thioguanine resistant clone (6T-C5) of HB4C5 cell line. Another, secreting human IgM-class anti-double-stranded DNA (ds DNA) monoclonal antibody, was a 5-bromodeoxyuridine resistant clone (5B-SU) of SU-1. Hybrid hybridomas were generated by fusing the 6T-C5 and 5B-SU lines and screened by HAT selection. Among many hybrid hybridomas, A9C11 cells produced bifunctional antibody having dual specificity for Cpase and ds DNA, and the light chains of the antibody consisted of the only ones derived from 5B-SU antibody, indicating that bifunctional antibody could be generated by heterologous association of heavy and light chains. PMID- 8518365 TI - In vitro priming of human lymphocytes. I. IL-2 and IL-4 requirements. AB - Induction of antigen-dependent IgM and IgG responses by human in vitro spleen cell cultures were supported by addition of defined lymphokines. Whereas exposure to IL-2 alone throughout both immunization and cultivation period supported the highest antigen-directed responses, antibodies of higher relative affinity to the immunizing antigen were secreted under conditions of shorter IL-2 exposure. Continuous presence of IL-2 supported the antigen-driven responses for up to 15 days, the later part of which was characterized by a very low relative affinity index value. IL-2 supported cultures produced up to 55 times and 36 times more IgM and IgG, respectively, than cultures without added IL-2. Addition of IL-2 neutralizing antibodies throughout the cultivation period abrogated all responses. Addition of IL-4 alone had negligible effect on the antigen-directed IgM responses but supported antigen-independent IgG responses. Neutralization of IL-4 alone had negligible effect on the IgM and IgG responses, whereas neutralization of IL-4 during IL-2 support, resulted in reduction of antigen dependency of responses. Delayed IL-4 neutralization (24 hours) restored some of the antigen sensitivity. IL-4 reduced IL-2-induced, antigen-directed immunoglobulin responses but supported increased antigen-induced, antigen directed responses, resulting in maximal antigen-specific responses. IL-4 reduced the IL-2-induced immunoglobulin production. IL-2 supported cell division, whereas IL-4 supported prolonged survival. Flow cytometry tests showed that IL-2 primarily induced CD8+ cells (T suppressor/cytotoxic) and OKT-10+ cells (plasma cells) cells, whereas the number of B1+ cells (B cells) decreased. IL-4 induced slight increases in the amount of B1+ cells and CD4+ cells (T helper). PMID- 8518366 TI - In vitro priming of human lymphocytes. II. Induction of antigen-specific IgG responses by repeated antigen stimulation. AB - A protocol by which a human spleen cell culture could be subjected to both a primary and a secondary type immunization in vitro has been developed. Primary immunized cultures required the addition of autologous fresh cells at the time of antigen re-exposure for generation of optimal antigen-specific IgG responses. Antigen re-exposure (secondary stimulation) was done 10 days after initial immunization. Subsequent responses were characterized by novel or greatly enhanced antigen-directed IgG responses compared to primary antigen stimulation. Re-exposure of antigen to 10-day old human spleen cell cultures, without addition of fresh cells, did not result in measurable responses. Lethal irradiation of the fresh cell component of a restimulation culture showed that the IgG responses were derived from the original culture and not the fresh cells. The presence of antigen during both the primary and the secondary immunization was a prerequisite for induction of antigen-directed IgG responses, as spleen cell preparations that had been cultivated without antigen, during the primary stimulation period or the secondary stimulation period or both, did not show antigen-dependent IgG responses after the secondary cultivation. Induction of IgG responses by restimulation was supported by IL-2, but only when IL-2 was added to both the primary and the secondary culture according to a strict protocol. IL-4 added during the second antigen exposure supported antigen-directed responses, whereas IL-4 added during the initial antigen exposure abrogated all antigen-dependent responses. PMID- 8518367 TI - Recombinant human antibodies: linkage of an Fab fragment from a combinatorial library to an Fc fragment for expression in mammalian cell culture. AB - The combinatorial phage library approach to immunoglobulin repertoire cloning recently made it possible to isolate gene fragments encoding human immunoglobulin G1 Fabs binding with high affinity to specific antigens. Here we describe the construction of genes encoding whole human anti-tetanus toxoid antibodies based on one of these gene fragments and the efficient expression of these constructs by co-transfection of separate heavy and light chain vectors into a Chinese hamster ovary cell line constitutively expressing a viral transactivator protein. This system will be generally useful for the rapid analysis of recombinant antibodies derived from combinatorial libraries. PMID- 8518368 TI - Preparation of antigen-binding monomeric and half-monomeric fragments from human monoclonal IgM antibodies against colorectal cancer-associated antigens. AB - The large size of human IgM monoclonal antibodies (MAbs) may impede the tumor localizing capacity. A procedure is described for the preparation of antigen binding monomeric (IgMm) and half-monomeric (IgM1/2m) fragments from two human IgM MAbs, COU-1 and D4213. The fragments retained binding activity against colon carcinoma. Six different reducing reagents (dithiothreitol, 2-mercaptoethanol, 2 mercaptoethylamine, L-cysteine, metabisulphite, ascorbic acid) were investigated over a range of concentrations, pHs, and incubation periods. The reduced IgM preparations were alkylated with iodoacetamide and fractionated by high performance gel permeation chromatography. The fractions were directly collected on ELISA plates coated with extracts of colon cancer cells. Antigen-binding IgMm and IgM1/2m fragments were obtained after treatment with mercaptoethanol, mercaptoethylamine, metabisulphite, and cysteine. IgMm and IgM1/2m fragments were also obtained after dithiothreitol treatment. These fragments were, however, nonreactive. The pH during the reduction was important for optimal yields of the fragments. The fragments obtained with 2-mercaptoethanol and mercaptoethylamine were most effective in binding to the cancer cell extract. The association constants per binding site for intact, monomeric, and half-monomeric COU-1 were by competitive inhibition assays estimated at 1.5 x 10(8) M-1, 3.1 x 10(8) M-1 and 4.0 x 10(6) M-1, respectively. The reduction of human IgM MAbs to IgMm and IgM1/2m fragments may facilitate the tumor localization when these are used in the diagnosis and therapy of cancer patients. PMID- 8518369 TI - Role of the anesthesiologist in vascular procedures. PMID- 8518370 TI - Perioperative myocardial ischemia in carotid endarterectomy under cervical plexus block and prophylactic nitroglycerin infusion. AB - Perioperative myocardial ischemia was evaluated in 36 consecutive carotid endarterectomy procedures carried out on patients with a high (72.2%) prevalence of ischemic heart disease. The procedures were performed under cervical plexus block plus a prophylactic intravenous nitroglycerin infusion. Findings of myocardial ischemia on perioperative (48 hours) continuous electrocardiogram recordings were correlated with preoperative cardiac status, perioperative continuous intra-arterial blood pressure measurements, and postoperative cardiac outcome. In two patients, ST segment analysis was un-interpretable because of bundle-branch blocks. Altogether, 64 episodes of significant ST segment depression were detected in 18 (52.9%) of the remaining procedures. In 8 (23.5%) procedures, ST segment depressions occurred either during carotid artery clamping at the time of the largest rise in blood pressure or within 2 hours of declamping, when blood pressure tended to decline. There were four (11.7%) postoperative cardiac events: three myocardial infarctions (one Q wave and two non-Q wave) and one episode of unstable angina pectoris. All four patients with cardiac events had early signs of myocardial ischemia either at the time of cross clamping, or soon after declamping of the carotid artery. All myocardial infarctions developed following prolonged (> 10 hours) myocardial ischemia, starting with the first 20 hours after surgery. Thus, ST segment depression occurring during clamping or soon after carotid declamping was associated with cardiac complications (sensitivity 100% and specificity 86.6%) and suggests the possible usefulness of on-line ST segment trend monitoring. PMID- 8518371 TI - Effects of cerebrospinal fluid drainage in patients undergoing thoracic and thoracoabdominal aortic surgery. AB - Cerebrospinal fluid (CSF) drainage has been reported to protect the spinal cord during surgical procedures requiring thoracic aortic cross-clamping. In 1986, CSF pressure monitoring and drainage was begun in an attempt to reduce the incidence of paraplegia associated with surgical repair of descending thoracic and thoracoabdominal aortic aneurysms (TAAA). These Group II patients (n = 50) were retrospectively compared to Group I patients (n = 49) who had undergone similar surgical procedures in the previous 3 years before CSF monitoring was introduced into this practice. Group II patients had intrathecal catheters placed for monitoring of CSF pressure and drainage of CSF to maintain the pressure < or = 15 mmHg. Seven patients (four in Group I, three in Group II) died before recovering from the anesthetic. Of the 47 patients in Group II who survived, none had clinically apparent complications such as an epidural hematoma or meningitis from the intrathecal catheter. The mean aortic cross-clamp time was 58.6 +/- 30.5 minutes (mean +/- SD) in Group I versus 65 +/- 42.6 minutes in Group II. Twenty three patients in Group I and 16 patients in Group II had a shunt to the distal aorta. To maintain a CSF pressure of < or = 15 mmHg in Group II, an average of 46.9 +/- 6.9 mL of CSF was withdrawn. Of the 45 survivors in Group I, 4 developed a spinal cord deficit; the number of patients with spinal cord deficit in Group II was 4 out of the 47 who survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518372 TI - Blood pressure management during aortic surgery: urapidil compared to isosorbide dinitrate. AB - The efficacy and hemodynamic effects of urapidil, an arteriolar vasodilator, and isosorbide dinitrate, a venodilator, were compared, when used for blood pressure control during abdominal aortic surgery. Urapidil is an alpha-adrenergic receptor antagonist with serotonin-1A receptor-agonist activity in the central nervous system. Hemodynamic profiles were recorded before and after the administration of the study drug (+/- 10 minutes before aortic clamping), 3 and 10 minutes following aortic clamping, and before and 3 and 10 minutes following the removal of the aortic clamp. Arterial and mixed venous oxygen contents were compared. Both groups of 18 patients were similar with respect to demographic profiles, anesthetic technique, and perioperative fluid therapy. Identical heart rate and blood pressure profiles were obtained. In contrast to isosorbide dinitrate, urapidil produced a 17% (P < 0.05) increase in cardiac index as a result of a 30% (P < 0.001) decrease in systemic vascular resistance before placement of the aortic clamp. In patients treated with urapidil, cardiac index was higher (P < 0.05) 10 minutes after aortic clamping, before removal of the clamp, and 10 minutes later. The arterio-venous oxygen content difference decreased from 3.2 +/ 0.8 mL O2/dL to 2.4 +/- 1.0 mL O2/dL (P < 0.01) following urapidil, but did not change during the administration of isosorbide dinitrate. It is concluded that urapidil is an effective and safe drug for the prevention of the hemodynamic consequences of aortic clamping. Compared to a venodilator (isosorbide dinitrate), urapidil offers the advantage of improving cardiac output and oxygen delivery. PMID- 8518373 TI - Does transesophageal echocardiography improve postoperative outcome in patients undergoing coronary artery bypass surgery? AB - The incidence and characteristics of ischemic episodes as detected by transesophageal echocardiography (TEE) and their relationship to postoperative myocardial infarction (MI) and adverse clinical outcome were studied in patients undergoing coronary artery bypass grafting (CABG). Seventeen of 50 patients had 21 TEE-defined ischemic episodes: 4 patients (8%) had 4 ischemic episodes in the pre-cardiopulmonary bypass (CPB) period, and 15 patients (30%) had 17 ischemic episodes in the post-CPB period, whereas 19 patients had 20 ECG ischemic episodes: 3 patients (6%) had 3 ischemic episodes in the pre-CPB period and 17 (34%) had 17 ischemic episodes in the post-CPB period. In 14 patients, ischemic episodes were detected by both TEE and ECG. Clinicians were made aware of the TEE data and appropriate treatments were undertaken during ischemic episodes: of the 15 patients with TEE-defined post-CPB ischemia, 4 had an additional saphenous vein graft placed, 8 had an intra-aortic balloon pump (IABP) inserted, 3 were given sublingual nifedipine, and 13 received nitroglycerin. These treatments resulted in improvement in regional wall motion abnormalities (RWMA) by the end of surgery in 11 of the 15 patients (73%), including the 4 with postoperative MI and 2 who died with cardiogenic shock. The authors conclude that: (1) significantly more patients had TEE-defined ischemic episodes in the post-CPB period (30%) than in the pre-CPB period (8%); (2) a poor graft and/or inadequate myocardial protection were strongly suggestive of post-CPB ischemia, which was significantly related to adverse outcome; and (3) TEE was a useful tool enabling detection of problem areas at an early stage and timely and appropriate treatment to support and sustain patients. PMID- 8518374 TI - Comparison of clinical and echocardiographic determinations of left ventricular dimension during weaning from cardiopulmonary bypass. AB - Twenty patients (age 45 to 78 years) were studied with ethical committee approval and informed patient consent during coronary artery bypass grafting. Transesophageal echocardiography (TEE) was used to validate a clinical measure of preload: inspection of the line of contact between the heart (acute margin) and the diaphragm. Immediately before going on cardiopulmonary bypass (CPB), with the cannulas and stay sutures in place, a small mark was made with the cautery on the diaphragm at the line of contact. After CPB the patients were transfused from the extracorporeal circuit to exactly the same level. At these two times, TEE recordings of the short axis of the left ventricle were performed and stored on videotape for later blinded evaluation off-line. The left ventricle short-axis area in end-diastole measured after CPB showed a close correlation to that measured before CPB, r = 0.88, P < 0.001. The regression line was close to the line of identity. The conclusion was that inspection of the line of contact between the heart and the diaphragm can be used clinically during weaning from bypass to obtain the same left ventricular end-diastolic volume as before CPB. PMID- 8518376 TI - Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: a comparison of computer-assisted versus manual infusion systems. AB - Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 +/- 139 ng/mL in the CACI group and 300 +/- 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 +/- 1.9 ng/mL in CACI and 6.3 +/- 4.6 ng/mL in the MCI group. The drug levels were lower (P < or = .05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 +/- 35.0 minutes, with a mean total fentanyl dose of 30.27 +/- 11.14 micrograms/kg. In the CACI group, the average duration of anesthesia was 230.8 +/- 44.1 minutes, with a mean total fentanyl dose of 34.61 +/- 5.40 micrograms/kg (P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518375 TI - Intraoperative measurement of saphenous vein bypass graft flow with transesophageal echocardiography. AB - The value of transesophageal echocardiography (TEE) for detecting saphenous vein coronary graft (SVG) flow was investigated. Thirty-five consecutive patients undergoing elective coronary artery bypass grafting (CABG) were studied intraoperatively. SVG flow characteristics obtained by TEE were compared with those gathered by an electromagnetic flowmeter (EMF). A total of 59 patent bypass grafts were examined. Pulsed-wave Doppler signals could be detected in 38/59 of the grafts studied (64.4%). The detection rate was the same for all types of grafts encountered (left anterior descending, right coronary, left circumflex, and lateral ventricular branches). The flow profiles obtained by TEE were very similar to those detected by EMF. Both profiles showed a bifid appearance with maximal flow in late diastole. The peak velocity seen in a SVG during diastole was 39.0 +/- 12.7 cm/sec. Graft volume determined by TEE correlated well with data obtained by EMF (r = 0.84). TEE is an attractive technique for noninvasively detecting phasic flow in SVGs; however, the flow detection rate is too low for the routine evaluation of graft patency. PMID- 8518377 TI - Isoflurane versus fentanyl: hemodynamic effects in cancer patients treated with anthracyclines. AB - Cancer patients treated with anthracycline derivatives are at risk for perioperative cardiovascular decompensation. The authors studied hemodynamic performance before, during, and after laparotomy in 14 anthracycline-treated patients with ovarian carcinoma. General anesthesia was maintained with 70% N2O in O2, and patients were randomized to receive supplementation with either isoflurane, 0.59% end-tidal +/- 0.04 (mean +/- SE), or fentanyl, 2.67 micrograms/kg +/- 0.49 as a loading dose, and a total dose of 7.16 micrograms/kg +/- 0.71. The degree of hemodynamic stability relative to the baseline was assessed. There was no obvious superiority of either technique prior to the skin incision. However, during and immediately after surgery, a clearer tendency for isoflurane-N2O to result in better hemodynamic stability was found. Isoflurane N2O demonstrated significantly smaller change scores in systemic vascular resistance (SVR) and cardiac index (CI). At the start of surgery, the isoflurane N2O change in SVR was 228.08 dyne.sec.cm-5 compared to 479.58 for the fentanyl patients, (P = 0.002); at the end of surgery the corresponding means were -12.09 and 703.14 dyne.sec.cm-5, respectively, (P = 0.002). Isoflurane-N2O was associated with significantly greater CI stability in the early postoperative period: the isoflurane-N2O mean change was -0.081 L/min/m2, versus -0.993 for the fentanyl-N2O patients, (P = 0.005). The authors conclude that anthracycline treated patients who do not have overt evidence of cardiomyopathy can be safely anesthetized with either anesthetic technique. However, during surgery and in the early postoperative period, an isoflurane-N2O technique appears to offer better hemodynamic stability. PMID- 8518378 TI - Comparison of axillary artery or brachial artery pressure with aortic pressure after cardiopulmonary bypass using a long radial artery catheter. AB - Arterial pressure measured in a peripheral artery may significantly underestimate central arterial pressure after discontinuation of cardiopulmonary bypass (CPB). Arterial pressure measured with a 50 cm radial artery catheter advanced into the brachial or axillary artery was compared to ascending aortic pressure in 31 patients before and after discontinuation of CPB. The radial artery catheter extended proximally into the brachial artery in 8/31 patients, and into the axillary artery in 23/31 patients. The patient's age, pre-CPB cardiac ejection fraction, and surgical procedures were similar in both groups. The systolic arterial pressure measured in the ascending aorta was found to be significantly different from that in the axillary artery after CPB, whereas the mean and diastolic pressures were not. The average aorta-to-axillary artery systolic pressure gradient was -3.0 +/- 4.0 mmHg, with no patient having a gradient greater than 10 mmHg. The systolic and mean arterial pressures measured in the ascending aorta were found to be significantly different from that in the brachial artery after discontinuation of CPB, whereas the diastolic pressure was not. The average aorta-to-brachial artery systolic pressure gradient was 6.9 +/- 6.9 mmHg, with 3/8 patients having a gradient greater than 10 mmHg. Long radial artery catheters, placed using the Seldinger technique, provide an accurate estimate of central aortic pressure after CPB when they are advanced into the axillary artery. Sites more distal than the axillary artery may result in significant underestimation of the central aortic pressure in these patients. PMID- 8518381 TI - Transesophageal echocardiographic diagnosis of a free-floating atrial thrombus. PMID- 8518380 TI - Effects of dobutamine and/or nitroprusside on the pulmonary circulation in patients with pulmonary hypertension secondary to end-stage heart failure. AB - Nine NYHA class III-IV patients awaiting heart transplantation (HTx) were studied with a right ventricular ejection fraction (RVEF) catheter. The first aim of the study was to explore the pulmonary and systemic circulatory effects of dobutamine (D) and/or nitroprusside (N) in these patients. The second aim was to search for the parameter(s) among those usually measured that best predicted RVEF. Baseline data were recorded after 30 minutes of stabilization. Then, three drug regimens were administered in a randomized order for 30 minutes each: D, 4 micrograms/kg/min; N, 0.25 to 1.0 micrograms/kg/min; and their combination. Significant changes in RV loading and function were observed with all three therapies. The combination of both drugs was superior to either drug alone. The best predictor of RVEF was pulmonary arterial elastance. The second best was pulmonary capillary wedge pressure (PCWP). Pulmonary artery pressures, pulmonary vascular resistances, and transpulmonary gradient (TPG) were of less predictive value, as shown by a multiple regression analysis. None of the drugs showed any selectivity for the pulmonary vasculature, because the ratio PVRI/SVRI was never changed significantly. Selective pulmonary arterial vascular smooth muscle relaxation is probably not the most important mechanism to explain the unloading and improvement in function of the RV with D and/or N. Improved myocardial pump function appears to be the major factor in unloading the RV via reduction of PCWP and mean pulmonary artery pressure with essentially no change in TPG. The RVEF catheter provides valuable additional information in the screening of HTx candidates for pulmonary hypertension. PMID- 8518379 TI - Optimal atrioventricular (AV) pacing interval during temporary AV sequential pacing after cardiac surgery. AB - Temporary dual chamber atrioventricular (AV) pacing is often used to increase cardiac output (CO) after cardiac surgery. The AV interval was varied to investigate the effect on CO in 13 patients. CO was computed from the Fick principle using mixed venous oxygen saturation (SvO2), arterial oxygen saturation (SaO2), hemoglobin, and oxygen consumption (VO2). AV intervals were varied randomly from 0.025 to 0.300 seconds in 0.025-second increments. The effect on CO from increasing the AV interval was dependent on the control CO. In all patients, as the AV interval was increased from 0.025 to 0.100 seconds, CO progressively increased. In most patients, the highest (optimal) CO occurred with AV pacing and averaged 300 mL/min greater than with atrial (A) pacing alone (P < .0001). In patients with a high initial CO (> 6.0 L/min), CO peaked and averaged 0.5 L/min more than with A pacing. CO was maximal for each of these patients at a unique AV interval between 0.100 and 0.225 seconds, and at intervals greater than 0.225 seconds CO decreased (P < .01). In patients with intermediate CO (4-6 L/min) at AV intervals greater than 0.100 seconds, a plateau in CO was reached. No consistent pattern was seen in patients with low initial CO (< 4.0 L/min). Maximal CO may be achieved by optimizing the AV interval in patients following cardiac surgery. The optimal AV interval is between 0.100 and 0.225 seconds and is different for each patient. Continuous SvO2 monitoring allows rapid evaluation of CO changes and optimization of the AV pacing interval. PMID- 8518382 TI - Diagnosis of an unsuspected large left atrial tumor with intraoperative transesophageal echocardiography in a patient scheduled for coronary artery surgery. PMID- 8518383 TI - Renal cell carcinoma in the inferior vena cava demonstrated by transesophageal echocardiography. PMID- 8518384 TI - Inadvertent transection of a pulmonary artery catheter during thoracic surgery. PMID- 8518385 TI - Case conference. Case 2--1993. Cardiopulmonary bypass in a patient with connective tissue disease (Ehlers-Danlos syndrome) and multiple, small arteriovenous fistulae. PMID- 8518386 TI - Pro: TEE is a routine monitor. PMID- 8518387 TI - Con: TEE is not a routine monitor in anesthesia for cardiac surgery. PMID- 8518388 TI - ST segment elevation following thymectomy. PMID- 8518389 TI - Safer cannulation of the internal jugular vein. PMID- 8518390 TI - Univent tube for thoracoscopic procedures. PMID- 8518391 TI - Persistent left superior vena cava diagnosed by transesophageal echocardiography. PMID- 8518392 TI - Cardiothoracic anesthesia for emergencies. PMID- 8518393 TI - Avoiding intra-arterial placement of the introducer sheath. II. PMID- 8518394 TI - Liver transplantation for primary sclerosing cholangitis versus primary biliary cirrhosis: a comparison of complications and outcome. AB - Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common cholestatic disorders in adulthood requiring hepatic transplantation. Although they run similar courses, they may have different problems before and after transplantation. The aim of this study was to compare pre- and post transplant complications and outcomes in these two similar but distinct patient groups. One hundred and seventeen adult patients underwent liver transplantation at our institution over a 6 year period, including 19 with PSC and 20 with PBC. Pre-transplant there were no significant differences in age, liver biochemistry, haematology or Child-Pugh scores between the two groups. The mean duration of disease before transplant was longer in PSC patients (11.7 vs 6.5 years; P < 0.05). The prevalence of septic cholangitis was greater in PSC (58 vs 5%; P < 0.01) as was the requirement for surgical or radiological interventional procedures, excluding cholecystectomy (53 vs 0%; P < 0.01). At transplantation, four patients with PSC had previously unrecognized cholangiocarcinoma. In the pre transplant period these four patients had uncontrolled biliary sepsis at the time of transplant vs five of 15 PSC patients without cholangiocarcinoma. Postoperatively, PSC patients had a greater prevalence of intra-abdominal sepsis requiring surgical or radiological intervention (42 vs 5%; P < 0.05). In comparison, patients with PBC had a high prevalence of skeletal complications (30 vs 10%; P < 0.05) particularly avascular necrosis (15 vs 0%). The prevalence of chronic rejection was similar in both groups (15%). Overall survival was higher in PBC patients (85 vs 63%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518395 TI - Rectal varices in extrahepatic portal hypertension. AB - Rectal varices, as distinct from haemorrhoids, occur due to high pressure in the inferior mesenteric venous system in patients with portal hypertension. The exact prevalence of rectal varices in extrahepatic portal hypertension is unknown. To determine this, 116 patients with extrahepatic portal hypertension were studied for the presence of rectal varices. These lesions were found in 103 (88.8%) patients. Bleeding from rectal varices occurred in 14.6% of patients. Massive bleeding requiring hospitalization and blood transfusion was not encountered. It is concluded that rectal varices are common in extrahepatic portal hypertension. Bleeding from them is uncommon, and often mild and self-limiting. The available literature is reviewed and the importance of recognizing the condition stressed. PMID- 8518397 TI - Persistent childhood diarrhoea: patterns, pathogenesis and prevention. AB - With improved management of acute episodes of infectious diarrhoea, increased attention is now being given to persistent diarrhoea and its nutritional consequences and associated mortality. Risk factors for the development of persistent diarrhoea include young age, malnutrition, impaired immune function, recent introduction of milk feedings, prior antimicrobial therapy and infection with pathogenic strains of Escherichia coli. Descriptive epidemiology indicates that 3-20% of episodes of acute diarrhoea in children in developing countries become persistent and cause about one-third to one-half of all deaths from diarrhoea. Environmental factors may be very important in causing persistent diarrhoea: these include undernutrition combined with the impact of living in highly contaminated environments and their effects on gastrointestinal microecology. Development of effective preventive strategies will depend on improved understanding of causes and pathogenesis of persistent diarrhoea. PMID- 8518396 TI - Fluorographic study on the oxidative stress in the process of gastric mucosal injury: attenuating effect of vitamin E. AB - In vivo oxidative change was visualized in the gastric mucosa of rats and the alteration was analysed by using a fluorescence microscope equipped with a digital imaging processor during the development of mucosal damage. Dichlorofluorescein (DCF)-associated fluorescence increased after the repeated electrical stimulation on the gastric artery (irritation), suggesting the occurrence of lipid peroxidation. The increase was enhanced in the mid-zone of two adjacent collecting venules. Allopurinol attenuated the oxidative stress in mucosa, showing the involvement of xanthine oxidase. Luminol-dependent chemiluminescence value in the blood taken from gastric vein was elevated by the irritation, suggesting that leucocyte-generated oxygen radicals also participate in this oxidative process. alpha-Tocopherol attenuated both the DCF activation and the increase in chemiluminescence value and prevented gastric mucosal injury. The present results suggest that alpha-tocopherol may be useful for the prevention of oxidative alteration in gastric mucosa. PMID- 8518398 TI - Doppler-controlled injection treatment of Dieulafoy's disease. AB - Dieulafoy's anomaly is a vascular malformation of the upper stomach, which typically causes massive and recurrent haemorrhage. Emergency endoscopy is the most effective method of diagnosing the disease. Until recently, the therapy of choice was surgical resection. Five patients with spontaneously stopped bleeding from Dieulafoy's ulceration were investigated. Transendoscopic Doppler ultrasound was used to identify arterial blood flow from the lesions. Local injection treatment was performed. Successful therapy resulted in the disappearance of arterial pulsations and no rebleeding occurred. The endoscopic Doppler is of diagnostic value in the evaluation of Dieulafoy's ulcer and enables control of endoscopic sclerotherapy. PMID- 8518399 TI - The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy. AB - Over the past 15-20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function. PMID- 8518400 TI - Management of non-ulcer dyspepsia. PMID- 8518401 TI - Management of irritable bowel syndrome. PMID- 8518402 TI - Helicobacter pylori and gastric cancer. AB - This review focuses on the similarities between the epidemiology of gastric cancer and the epidemiology of Helicobacter pylori. Their demographic patterns and the results of studies regarding familial and environmental risk factors are described. The association of gastric cancer and H. pylori infection with both gastric ulcer and chronic atrophic gastritis is also characterized and the possibility that a H. pylori infection could lead to gastric cancer is discussed. PMID- 8518403 TI - Multiple 'cysts' in the entire pancreas in a case of cystic adenocarcinoma of the pancreas. AB - A case of multiple 'cysts' coexisting with cystic adenocarcinoma in the pancreas is presented. The cysts were lined by epithelium consisting of either cuboidal and flat cells or mucinous cells, which formed a papillary pattern; the former cells were more frequent and the latter were considered to be hyperplasia. The pathological findings for the diffuse multiple cysts suggested cystic disease caused by ductal stenosis, while the mucinous cells may have been related to the malignant tumour. PMID- 8518404 TI - The future of new pure antiestrogens in clinical breast cancer. AB - The rationale for seeking to identify new pure antiestrogens was based on the recognition that existing antiestrogens, exemplified by tamoxifen, all possess partial agonist (estrogenic) activity. Conceptually, pure antiestrogens should be more effective than tamoxifen in ablating the mitogenic action of estrogens on breast tumor growth. The discovery and properties of the pure antiestrogens ICI 164,384 and ICI 182,780 are described and contrasted with those of tamoxifen. Key characteristics of these compounds which may be of particular relevance to their therapeutic application in the treatment of breast cancer are described. These include experimental data which predict efficacy in patients whose disease recurs during tamoxifen treatment, and the potential for pure antiestrogens to demonstrate greater efficacy than tamoxifen in first-line treatment of advanced breast cancer. The data imply that gains in efficacy could emerge as more rapid, more complete, or longer-lasting tumor remissions. Clinical trials with ICI 182,780 will reveal whether one or more of these predictions is correct. PMID- 8518405 TI - Selenium and the risk of postmenopausal breast cancer in the DOM cohort. AB - Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a 'preventive-potential' of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk. The cohort consisted of 5577 women aged 55-70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening. represent 'recent' tumours since all women had a negative screening mammogram 3-5 years previously. No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among 'future' cancer cases was observed. As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518406 TI - Epidermal growth factor receptor and prognosis in human breast cancer: a prospective study. AB - The prognostic value of Epidermal Growth Factor Receptor (EGFR) in human breast cancer is a matter of debate. We conducted a prospective study that included 459 unselected patients with primary breast cancer (median follow-up 24 months) to assess the prognostic value of EGFR. EGFR was assessed using a standardized radioligand binding assay. Univariate analysis showed that EGFR is a factor indicative of a poor prognosis with respect to Disease Free Survival (DFS, P = 0.03) and Overall Survival (OS, P = 0.002), if an EGFR level of 50 fmol/mg of membrane protein is introduced as a cut-off for EGFR-positivity. Multivariate analysis showed that EGFR was not an independent factor. This prospective study shows that EGFR, although not an independent factor, is indicative of poor prognosis in human breast cancer. PMID- 8518407 TI - Comparative effect of embryonic mouse fibroblasts (Balb/c-3T3) on the proliferation of hormone-dependent (T-47D) and hormone-independent (MDA-MB-231) human breast cancer cell lines. AB - The effects of cellular extracts (CE) and conditioned medium (CM) of embryonic mouse BALB/c-3T3 (clone A 31) cells on the proliferation and DNA content of hormone-dependent T-47D and hormone-independent MDA-MB-231 breast cancer cell lines were explored. After 6 days of culture, CE and CM provoke an intense proliferative effect in T-47D cells which correlates with DNA content. In contrast, in the MDA-MB-231 cells a significant inhibitory effect was observed. For both CE and CM the action was dose-dependent. In the T-47D cells, the CM can abolish the inhibitory effect provoked by the potent antiestrogen ICI 164,384. It is concluded that mouse embryonic BALB/c-3T3 cells contain factors which can stimulate or inhibit the growth of human mammary cancer cells. PMID- 8518408 TI - Toremifene and tamoxifen in advanced breast cancer--a double-blind cross-over trial. AB - Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double blind, cross-over study. 66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40 mg/day or TOR 240 mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10 41%) and with TAM 42% (95% confidence limits 25-61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of over-looking a response rate of 20% or more is less than 1%. In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer. PMID- 8518409 TI - Growth and metastasis of human breast carcinomas with Matrigel in athymic mice. AB - Immunodeficient athymic mice with human tumor xenografts provide an important in vivo experimental model for cancer research. However, only a limited number of tumor types grow in these animals. For human breast carcinomas, the incidence of tumor-take is 6-15%. Recently, increased incidence of xenograft development in mice has been reported for various human tumors when the tumors were coinjected with Matrigel. We studied the development of human breast carcinoma xenografts in athymic mice with and without coinjection of Matrigel. Tumors developed in only 7.3% of enzyme-dispersed tumors injected subcutaneously in saline solution alone. None of these tumors metastasized to distant sites. On the other hand, 50% of enzyme-dispersed tumors coinjected with Matrigel developed xenografts; four out of five of these tumors metastasized to distant sites. Our data from the recent study suggest that, in athymic mice, Matrigel not only enhanced breast tumor growth but also facilitated tumor metastasis. PMID- 8518410 TI - Structural and functional studies of insulin receptors in human breast cancer. AB - We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer and normal breast tissues, insulin receptor mRNA consisted of two major species of approximately 11.0 and 8.5 kilobases. The size of the insulin receptor alpha subunit was determined by 125I-insulin cross-linking followed by immunoprecipitation and polyacrylamide gel electrophoresis; a value of 135kDa was observed for receptors from both breast cancer and normal breast tissues. The functional binding ability of insulin receptors from cancer tissues was slightly lower as compared to normal tissue derived insulin receptor (% B/T = 2.22 +/- 0.50 per ng of insulin receptor as determined by radioimmunoassay vs. 2.96 +/- 0.49, mean +/- S.E.M.). The concentration of insulin that caused half maximal inhibition of 125I-insulin binding was very similar for both cancer and normal breast receptors (80pM). The size of the insulin receptor beta subunit as determined by receptor autophosphorylation was 95kDa. Basal and maximal insulin (100nM) stimulated receptor tyrosine kinase activity, in terms of both receptor autophosphorylation and phosphorylation of an exogenous substrate, was similar in malignant and normal breast tissue derived insulin receptor. Also, a very similar insulin stimulated Km value for ATP was showed by the tyrosine kinase of insulin receptors from breast cancer and normal breast tissue (11.1 and 10.8 microM ATP, respectively). However, in insulin receptors from breast cancer tissue the average tyrosine kinase sensitivity to insulin, as calculated on the exogenous substrate, was higher, although not significantly, with respect to normal breast tissue (ED50 at 0.28 +/- 0.09 and 1.08 +/- 0.33 nM insulin, respectively). A similarly different sensitivity to insulin was observed also for receptor autophosphorylation. In conclusion, this study demonstrates that breast cancer tissues have an increased number of structurally and functionally normal insulin receptors. In some breast cancer tissues, however, the sensitivity of the receptor tyrosine kinase activity to insulin is greatly increased. These data suggest that, in vivo, the mitogenic effect of insulin may play a role in the biology of certain breast cancers. PMID- 8518412 TI - p53 associated with cathepsin D in primary breast cancer. AB - The p53 protein was identified in primary breast carcinomas by specific binding of PAb1801 and PAb240 antibodies. Using sodium dodecyl sulfate electrophoresis followed by immunoblotting on nitrocellulose membrane, the p53 protein was identified in 36 nuclear fractions obtained from 60 primary breast cancers; semiquantitation of p53 was performed by densitometric scanning. The total cathepsin D content, the estrogen and progesterone receptor concentration values and the axillary lymph node involvement were also assessed. Tumors expressing p53 had significantly higher levels of cathepsin D than those in which p53 was undetectable. p53 expression was strongly associated with low or negative estrogen receptor values; progesterone receptor concentrations were also significantly higher in p53-negative tumors than in those tumors with detectable p53 levels. Finally, a significant relationship between p53 expression and lymph node metastasis was observed. It was concluded that a positive association between p53 and cathepsin D values exists which is of prognostic interest in that both cathepsin D and p53 are associated with a high tumor grade and metastatic activity. PMID- 8518413 TI - Anti-erythrocyte autoimmunization in hydatid disease. AB - A 73-year-old man with hydatid disease developed autoimmune hemolytic anemia due to IgM cold agglutinin with anti-I specificity. Hemolysis decreased after initiating mebendazole therapy. The cysts notably diminished in size and the red cell autoantibodies disappeared at the end of this treatment. On the basis of these observations, 44 patients with hydatid disease were investigated. One patient showed IgM cold autoantibody with no signs of anemia. In addition, cleavage fragments of C3 were detected on the erythrocyte membranes of 6 patients, following chronic activation of the complement system. We suggest that parasitic antigens may evoke antibodies cross-reacting with the red blood cells of the host. PMID- 8518411 TI - Toward a molecular understanding of human breast cancer: a hypothesis. AB - A rate limiting step in most metastatic breast cancers is the development of unlimited proliferative potential by mammary epithelial cells. We describe mechanisms by which these cells can attain this state. The two independent mortality mechanisms controlling fibroblast senescence and immortalization (M1 and M2) are also found in human mammary epithelial cells. However, although both p53 and Rb are involved in the M1 mechanism of fibroblast cellular senescence, in human mammary epithelial cells only p53 is involved. The M1/M2 mechanisms may be induced by the gradual loss of telomere ends that occur as normal cells divide. Loss of telomere ends may result in genomic instability and in altered gene expression due to heterochromatin changes in subtelomeric regions. Events which can abrogate p53 functions are described, as is the current state of knowledge about the function of p53. All these factors are included in a molecular model for the onset of breast cancer. PMID- 8518414 TI - Retinoids and tamoxifen in breast cancer chemoprevention. AB - Chemoprevention is a new branch of oncology which aims to use chemical agents to reduce the incidence of malignant diseases in humans. On the basis of a growing mass of experimental data, it is now felt that the importance of early, precursor lesions of clinically symptomatic cancer should be recognized. Just as in cardiovascular disease, there is now major emphasis on the natural history of tumors and some authors believe that the actual disease process is carcinogenesis, rather than cancer. Indeed, as the chemoprevention of cardiovascular illness with pharmacological agents that either lower blood cholesterol or prevent platelet aggregation is widespread, the effectiveness of different chemical compounds in preventing cancer or, at least in delaying its onset, is presently under investigation. For breast cancer, various agents have been suggested as having chemopreventive effects: vitamins C and E, difluoromethylornithine, selenium, retinoids and antiestrogens. Among retinoids, 4-(N-hydroxyphenyl)retinamide, fenretinide, is at present the most promising molecule, due to its ability to concentrate in the mammary gland. Attention has recently been focussed on tamoxifen because of its effectiveness in reducing the incidence of contralateral tumors in breast cancer patients. Finally, the recent discovery of the steroid receptor superfamily is expected to stimulate further research into combination chemoprevention (the use of multiple agents to achieve synergistic effects while diminishing toxicity). As retinoids and tamoxifen both increase the synthesis or activity or transforming growth factor-beta, a cytokine which is a potent inhibitor of epithelial cell proliferation, tamoxifen and fenretinide are now proposed as the first model of combination chemoprevention in breast cancer. PMID- 8518415 TI - Human thymic epithelial cells: adhesion molecules and cytokine production. AB - The ability to culture human thymic epithelial cells has greatly facilitated studies of direct cell-cell interaction between thymic epithelial cells and T lymphocytes in vitro, as well as cytokine production and regulation of cytokine production. In vitro, human thymic epithelial cells bind to T lymphocytes via two adhesion pathways: CD2-lymphocyte function-associated antigen-3 and lymphocyte function-associated antigen-1-intercellular adhesion molecule-1. Cultured human thymic epithelial cells produce interleukins-1 alpha, -1 beta, -3, -6 and -8, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, leukemia inhibitory factor and transforming growth factor-alpha. Production of thymic epithelial cell-derived cytokines is regulated by both adhesion molecules (lymphocyte function-associated antigen-3) and soluble factors via both autocrine (interleukin-1 alpha, transforming growth factor-alpha) and paracrine (interleukin-4, interferon-gamma) pathways. Transforming growth factor-alpha and epidermal growth factor regulate various cytokine mRNA at a post-transcriptional level by increasing cytokine mRNA stability. PMID- 8518416 TI - CD8 and beta 2-microglobulin-free MHC class I molecules in T cell immunoregulation. AB - Intracellular assembly of MHC class I heavy chains with beta 2-microglobulin occurs prior to the expression of the antigen-presenting complex on the cell surface. The association of beta 2-microglobulin with newly synthesized class I heavy chains is thought to be a strict prerequisite for their transport to the cell surface. However, MHC class I molecules not associated with beta 2 microglobulin (beta 2-microglobulin-free class I heavy chains) have been detected on the surface of activated lymphoid cells. These molecules have different conformations. Therefore, their interactions with other membrane proteins and biological functions may be different from those assigned to beta 2-microglobulin associated MHC class I molecules. The two forms of MHC class I molecules on the surface of activated cells can self-associate and also form complexes with distinct proteins. Upon interaction with the appropriate ligands these molecular complexes transduce signals regulating cell activation. The ligand for beta 2 microglobulin-free class I heavy chains appears to be soluble CD8. A model is presented describing a novel mechanism of immunoregulation mediated by both soluble and membrane-bound forms of CD8 and beta 2-microglobulin-free class I heavy chains. PMID- 8518417 TI - Predictive value for thrombotic disease of plasminogen activator inhibitor-1 plasma levels. AB - Plasminogen activator inhibitor-1 plays a major role in the fibrinolytic system as the main physiological inhibitor of both tissue-type and urinary-type plasminogen activators. The inhibitor is present in plasma in small amounts and derives mainly from endothelial cells. Positive correlations have been reported between plasma levels and different parameters, such as serum triglycerides, insulin plasma levels and body mass index. Moreover, high plasma inhibitor concentrations have been observed in different disease states, but it must be stressed that plasminogen activator inhibitor-1 behaves as an acute-phase reactant and measurement of plasma levels is not significant in the acute phase of the disease. A possible predictive value of inhibitor levels for thrombotic events such as deep vein thrombosis and ischemic heart disease has been studied. On the basis of available studies, the predictive value is not clear for venous thrombosis, whereas plasminogen activator inhibitor-1 levels can predict some coronary events, at least in subgroups of young patients with a first myocardial infarction. It remains to be established if treatments able to reduce plasma inhibitor levels lead to a decrease in the risk of thromboembolic events. PMID- 8518418 TI - Expression and modulation of a mononuclear phagocyte differentiation antigen (PAM 1) during in vitro maturation of peripheral blood monocytes. AB - Human macrophages obtained by in vitro maturation of peripheral blood monocytes express a surface antigen, PAM-1, recognized by a monoclonal antibody and typical of pulmonary alveolar and tissue macrophages. PAM-1, undetectable in freshly isolated peripheral blood monocytes, was expressed in monocyte-derived macrophages after 3 days of in vitro adherent culture and was maximal after 14-15 days (50%-60% of positive cells). Similar levels of PAM-1 positivity were observed in non-adherent monocyte-derived macrophages suggesting that cell adhesion was not a critical requisite for the expression of this antigen. Bacterial lipopolysaccharide and a monocyte chemotactic protein preparation respectively suppressed and upregulated PAM-1 expression in monocyte-derived macrophages. In contrast, interferon-gamma, although enhancing the levels of class II HLA-DR antigen in monocyte-derived macrophages, did not influence the kinetics of appearance and the levels of PAM-1 in these cells. Thus, expression of PAM-1, which is restricted to certain stages of the monocyte-macrophage differentiation pathway, is also differentially modulated by activation signals, which can be present in the micro-environment of inflammed tissues. PMID- 8518419 TI - Effects of nicotinic acid treatment on glyceride formation and lipolysis in adipose tissue of hyperlipidemic patients. AB - Thirty-one weight-stable patients with different types of hyperlipoproteinemia were treated daily with 4 g nicotinic acid for 6 weeks. Effects of this therapy on adipose tissue metabolism were evaluated. By using biopsy specimens of subcutaneous adipose tissue, fatty acid and glucose incorporation into adipose tissue glycerides were measured in vitro as well as glycerol and fatty acid release, which allowed us to estimate adipose tissue lipolysis. The amount of fatty acids produced by lipolysis and thereafter utilized within adipose tissue without being released (fatty acid retention) was estimated. Fatty acid and glucose incorporation into adipose tissue, glycerol release and fatty acid retention values increased, but serum triglyceride levels decreased (all P < 0.001) after nicotinic acid treatment. The change in fatty acid incorporation was positively correlated with changes in glucose incorporation into adipose tissue (r = 0.53, P < 0.01) and fatty acid retention (r = 0.76, P < 0.001). Although adipose tissue lipolysis, measured as glycerol release, increased, the lipolyzed fatty acids were retained in adipose tissue, suggesting an enhanced synthesis of glycerides both from exogenous and endogenous sources. The increase in fatty acid incorporation into adipose tissue indicates that the decrease in serum triglyceride levels produced by nicotinic acid treatment may partly be due to the fact that this drug promotes incorporation of fatty acids, derived from lipoprotein-carried triglycerides in the blood, into adipose tissue glycerides. PMID- 8518420 TI - Anti-oxidized low-density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers. AB - We have developed a solid-phase enzyme immunoassay for anti-oxidized low-density lipoprotein antibodies. Most sera showed some degree of non-specific binding to plates coated with oxidized low-density lipoprotein and the autoantibodies to oxidized low-density lipoprotein often appeared to have a relatively low affinity. To differentiate between specific and non-specific binding each sample was tested untreated and after absorption with oxidized low-density lipoprotein. The optical densities obtained with dilutions of the absorbed sample were considered to reflect non-specific binding and were subtracted from values obtained with identical dilutions of the unabsorbed sample, to yield corrected values from which the concentrations of anti-oxidized low-density lipoprotein antibody were calculated. Similar absorptions with native low-density lipoprotein and oxidized human serum albumin failed to induce a significant reduction in binding to immobilized oxidized low-density lipoprotein proving that the antibodies measured by this assay are primarily specific for oxidized low-density lipoprotein. We studied sera from two groups of individuals: (1) 33 subjects submitted to coronary angiography and split into two subgroups depending on the degree of coronary stenosis and (2) 64 healthy individuals also split into two subgroups according to lipid levels. Anti-oxidized low-density lipoprotein antibodies were detected both in patients and healthy individuals. Higher levels were detected in patients with moderate coronary disease and hyperlipemic healthy individuals, but the differences between patients and healthy volunteers or between their respective subgroups did not reach statistical significance. Our results suggest that autoantibodies to oxidized low-density lipoprotein are relatively frequent in both symptomatic and asymptomatic individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518421 TI - Helicobacter pylori toxin inhibits growth and proliferation of cultured gastric cells-Kato III. AB - The presence of Hp is strongly associated with chronic type B gastritis and peptic ulcer disease. The pathogenic mechanisms of Helicobacter pylori (Hp) infection are still unclear. Hp produces toxins which are capable of exerting cytotoxic effects. Whether these changes result in decreased cell proliferation has not been previously demonstrated. Our results show that a 2 hour incubation of gastric Kato III cells with Hp cytotoxin produces a 60% decrease in cell proliferation. In conjunction with a decreased cell proliferation, cell growth is also decreased on days 5 and 7. The ability of Hp to retard cell proliferation may play a role in the pathogenesis of Hp-associated diseases by inhibiting the normal mechanisms of gastric mucosal protection and repair. PMID- 8518422 TI - Interleukin-1 and experimental gastric ulcer healing in the rat. AB - The involvement of inflammation in peptic ulcer development and healing attracts growing interest. Since lymphokines, in particular interleukin-1 (IL-1), as ubiquitous mediators of inflammation are currently intensively studied in the gastrointestinal tract, we assessed the effect of this cytokine as well as that of a specific IL-1 release inhibitor (IX 207-887 (IX)) on development and healing of experimental gastric ulcers. After a single dose of IL-1, 4 micrograms/kg, i. p., basal acid secretion was almost completely inhibited for 4 hours in conscious chronic gastric fistula rats. In a first study, following induction of a 7 mm wide cryo-ulcer in the gastric corpus, three groups of 24 rats were treated either with a non-acid inhibitory dose of IL-1 (0.4 microgram/kg) or with an antisecretory regimen (4 micrograms/kg) b.i.d. or saline control. Ulcer size did not differ from that of control animals, neither after 24h nor 7 days. Similarly, IX applied daily (20 mg/kg/s.c) from 5 days before ulcer induction and continued thereafter for 15 days had no effect on ulcer development or healing. Despite its anti-inflammatory property IX produced no macroscopically visible damage on the gastric or intestinal mucosa and may therefore offer a higher safety profile within the gastrointestinal tract than conventional non-steroidal anti inflammatory drugs. PMID- 8518423 TI - Future treatment of peptic ulcer: is there room for anti-infective drugs? AB - Several major Laboratories have recently given up their search for uncovering innovative antiulcer drugs despite the fact that none of the available drugs meet the ideal aims of therapy: to relieve pain, to heal the ulcers and to prevent the recurrences. Furthermore, no single antiulcer drug has proven effective in managing ulcer-related complications or ulcers associated with oncology and sclerotherapy treatment. Recent research suggests that the eradication of H. pylori infection is associated with decreased rate of duodenal ulcer recurrences, however, appropriate and convenient eradication therapy needs to be developed. Moreover, we must also continue to search for ideal drugs effective for the treatment of ulcers and their complications. PMID- 8518424 TI - Nitric oxide inhibits the myoelectric activity of the small intestine in dogs. AB - Intestinal motility in fasted animals shows cyclic changes (MMC) that are interrupted by feeding. The aim of this study was to determine the possible implication of nitric oxide (NO) (that was proposed as nonadrenergic noncholinergic neurotransmitter) in the motor components of MMC in 5 conscious dogs equipped with monopolar electrodes implanted along the small bowel. In fasted dogs with typical MMCs, L-NNA (an inhibitor of NO synthase) (5 mg/kg-h i.v.) decreased the MMC interval from control 80 +/- 7 to 60 +/- 4 min and increased significantly the spike activity. Infusion of L-arginine (L-Arg) (a substrate of NO synthase) (10 mg/kg-h i.v.) increased the MMC interval from control 79 +/- 7 to 96 +/- 8 min and reduced the slow waves with spikes by about 25%. Similar but transient effects were observed when glycerin trinitrate (GTN) (a donor of NO) (1 mg/kg-h) was administered. After ingestion of meal, the MMC cycles were replaced by irregular spike activity with an average of about 35% slow waves with spikes. Infusion of L-Arg (10 mg/kg-h) reduced by about 90% the postprandial spike activity. Also, infusion of GTN (1 mg/kg-h) strongly reduced the postprandial spike activity. L-NNA in fed dogs caused an initial increase in spike activity followed by phase III-like activity. Similar effects were obtained when L-NNA was infused in dogs with fed-like motility patterns induced by i.v. infusion of caerulein (75 pmol/kg-h). L-NNA added to L-Arg infusion reversed in part the changes of intestinal motility patterns induced by L-Arg. We conclude that NO system exerts a tonic inhibitory influence on intestinal myoelectric activity by reducing the frequency of MMC pacesetter and by suppressing the postprandial spike activity. PMID- 8518425 TI - Circadian variation of mitochondrial succinic dehydrogenase and microsomal cytochrome P-450 dependent monooxygenase activity in the liver of sexually immature and mature rats. AB - The experiments were carried out on 60-day and 6-month old male Wistar rats within 48 h in one season of the year (autumn). Material was collected every four hours, beginning from 10:00 a.m. The present results indicate that the fluctuations of cytochrome P-450 content in liver microsomes in both age groups occurred in a 12 h rhythm with peaks at 10:00 and 22:00. Similarly, the activity fluctuations of NADPH-cytochrome c reductase showed the 12 h rhythm, with maximal values at 10:00 and 22:00, too. The cytochrome b5 content in a younger group of rats oscillated apparently in the 12 h rhythm with the maximal values at 06:00 and 18:00. The activity course of cytochrome b5 in 6-month-old rats revealed a 24 h rhythm and two maxima of the activity were found: the first one at 14:00 and the second one at 02:00. NADH-cytochrome b5 reductase in both age groups showed a 24 h rhythm, also the activity fluctuations of succinic dehydrogenase showed a tendency to 24-h rhythmicity, and the differences between minimal and maximal values were statistically insignificant. The results of our experiment have shown some correlations between the activity of microsomal system of mixed-function oxidases and mitochondrial respiratory enzyme. PMID- 8518426 TI - Enkephalinase activity in the intestinal epithelial cells of the fetus of 19 days and their immortalized and transformed counterparts the SLC-cell lines. AB - Enkephalinase (EC 3.4.24.11), an enzyme widely distributed in brain and peripheral tissues of human and various animal species, was measured in the intestinal fetal cells and in the intestinal epithelial cells of adult rat, where its activity was respectively 96,1 +/- 10,18 fmol/mg protein and 52,27 +/- 8,43 fmol/mg protein. The immortalized cell lines: SLC-11 (after transfection with the plasmid containing oncogene from the human adenovirus type 2-E1A), SLC-21 (plasmid containing oncogene from polyoma virus) and SLC-41 (plasmid containing oncogene from simian virus 40 large tumor antigen) presented relatively strong enkephalinase activity; it was respectively 28,3 +/- 1,7, 37,9 +/- 3,6 and 49,3 +/- 3,1 fmol/mg protein. The cells of SLC-12T and SLC-44T lines, obtained after transfection with the mutant Ha-ras-1-gene and possessing tumorigene potency have the enkephalinase activity very decreased: 1,6 +/- 0,9 and 8,7 +/- 3,2 fmol/mg protein (p < 0,001). This interesting properties of the tumorigene cells may constitute a new subject of investigations in the carcinomas therapy. PMID- 8518427 TI - Glycosulfatase activity of Helicobacter pylori towards gastric sulfomucin: effect of nitecapone. AB - A glycosulfatase activity towards human gastric sulfomucin was identified in the extracellular material elaborated by H. pylori, a pathogen implicated in the etiology of gastric disease. The purified enzyme exhibited maximum activity at pH 5.7 in the presence of 0.3% Triton X-100 and 100mM CaCl2, and displayed on SDS PAGE an apparent molecular weight of 30kDa. The H. pylori glycosulfatase effectively caused desulfation of N-acetylglucosamine-6-sulfate and galactose-6 sulfate of the carbohydrate chains of mucins, as well as that of glucose-6 sulfate of glyceroglucolipids, but was ineffective towards galactosyl -and lactosylceramide sulfates which contain galactose-3-sulfate. The glycosulfatase activity towards human gastric sulfomucin was inhibited by an antiulcer agent, nitecapone, which at its optimal concentration (100 micrograms/ml) caused a 61% decrease in mucin desulfation. The results show that H. pylori through its glycosulfatase activity causes desulfation of sulfated mucins and glyceroglucolipids of the protective mucus layer, and that nitecapone is able to interfere with this detrimental action. PMID- 8518428 TI - Comparative analysis of effects of imidazoline drugs on isolated rat heart atria. AB - Effects of cumulative concentrations of 16 known imidazoline and 2 imidazole drugs on amplitude and rate of spontaneously beating isolated rat heart atria were measured and related to the respective effects induced by norepinephrine. In addition, the effects of fixed concentrations of the agents on the responses evoked by cumulative concentrations of norepinephrine were determined. In general, imidazolines classified as alpha 1-adrenoceptor agonist showed positive inotropic activity providing evidence for involvement of the alpha 1-adrenoceptor in mediating cardiac contractility. Negative chronotropic effect was common for the imidazolines studied, including alpha 1-adrenoceptor agonists, alpha 2 adrenoceptor agonists, alpha 1/alpha 2-adrenoceptor antagonists and antazoline- an antihistaminergic imidazoline devoid of adrenoceptor affinity. On the other hand, the imidazole derivative, medetomidine, showed a weak positive chronotropic activity. Negative chronotropic properties appeared to be independent of the alpha-adrenoceptors and may result from the membrane stabilizing action, involving probably the sodium channel blockade. PMID- 8518429 TI - [Effectiveness of a community-based education program on blood pressure reduction for cardiovascular disease prevention]. AB - To evaluate the effectiveness of lifestyle modification community-based programs on blood pressure reduction, blood pressure changes were examined according to frequency of attendance at these adult classes. The subjects were 1,017 men and women aged 40-69 who participated in a survey from 1985 to 1987, whose blood pressure was > = 140 mmHg for systolic, and/or > = 90 mmHg for diastolic and/or with antihypertensive medication use in the earlier 1981-1984 surveys. Adult classes were conducted eleven times between 1982 and 1987, emphasizing primarily reduction of salt intake, weight control if necessary, and alcohol modification. Blood pressure changes between 1981-1984 and 1985-1988 were examined in relation to the number of classes attended, stratified by antihypertensive medication use. In the group with no medication use in both surveys (n = 347), there was a significantly larger decline in systolic and diastolic blood pressures with an increase in the number of classes attended (p < 0.001). A similar trend was observed in other groups: a starting medication group (n = 198), a quitting medication group (n = 100) and a continuous medication group (n = 372). The blood pressure trend in the no medication group remained significant after controlling for age, initial blood pressure, follow-up years and the number of follow-up screenings attended. For the no medication group, there was no significant association between the number of classes attended and changes in relative weight index and alcohol intake. The proportion of persons reporting dietary modification of reduction in salt was larger, and mean 24-hour urine sodium excretion was smaller, with increasing number of classes attended in the 1985 1988 surveys. Furthermore, the proportion of persons who were able to reduce salt intake between the two survey periods was higher with an increase in the number of classes attended. Mean urine sodium excretion was smaller in those who reported reduction of salt intake than those who did not. Although this study is not a randomized controlled trial, these results suggest that a community-based education program of adult classes can be effective in reduction of blood pressure levels through modification of diet. PMID- 8518430 TI - [Relationship of in- and outpatient medical expenditure for the elderly to socioeconomics, medical services, and health and welfare projects]. AB - In order to clarify what factors are associated with per capita medical care expenditure for those aged 65 years and over, for inpatients and outpatients respectively, correlation analyses were performed using several indices of medical services, socioeconomics, medical supply, health and welfare projects for fiscal 1989 among 99 administrative areas in Gifu Prefecture. The expense for inpatients was correlated with the service-acceptance rate, while on the other hand the expense for outpatients was correlated with average cost of medical receipts. Two major factors were number of physicians per person aged 65 years and over and per capita income. For outpatients, population density and per capita amount of subsidy for "elderly welfare projects" were significantly correlated with medical expenditure, with the latter showing a negative correlation. Multiple regression analyses indicated that these factors were independently correlated with the expenses. These findings indicate that expenses for inpatients and outpatients have different construction, with each being associated with different factors. PMID- 8518431 TI - [Difference in impact of social support on morale and medical utilization between elderly with low activity of daily living and elderly with high activity of daily living]. AB - The impact of social support on morale and medical utilization among elderly with low activity of daily living (ADL) were compared to those of elderly with high ADL. Social support was measured from three aspects--receiving emotional support, receiving instrumental support, and providing emotional support, all based on the individual perception of the elderly person. Subjects were 125 persons with low ADL obtained from a national random survey of 3,288 people aged 60 and over. They were matched with 125 high ADL people with the same age categories and sex. 1. Persons with low ADL had lower PGC-Morale Scale Score than persons with high ADL. In the low ADL group, the percentage who went to a physician less than 3 times during the past three months was 30.6%. 2. In the low ADL group, people who perceived receiving high emotional support to others also scored high in PCG Morale Scale. People who perceived being able to provide emotional support to others also scored high in PCG-Morale Scale. In the high ADL group, only perception for receiving emotional support had an impact on the score. 3. Social support of any kind did not have an impact on medical utilization in either group. PMID- 8518432 TI - [Attitudes toward handicapped children--a study comparing parents of handicapped children and others, in the case of Down syndrome]. AB - The physically handicapped have received increasing attention in recent years. Since 1981, the International Year of Handicapped Persons, a number of administrative measures have been passed and the rights of handicapped have been recognized. However some problems still remain. In this study, conducted in 1990, the knowledge people have about congenital defects and their thinking regarding the social system for the handicapped were examined. A similar survey of parents of children with congenital defects was conducted to understand problems they encountered in the medical care and education of their child. Eighty-four parents of Down Syndrome children (DS) and 118 controls including housewives, female office workers, and students were surveyed. Results showed that 44% of mothers of DS wanted their husbands to participate more intensively in the medical care and education of their child. A slight gap in knowledge between the parents and the controls was seen. Of the controls, 12% asserted that the relationship of the handicapped and the non-handicapped should be equal. However, some of controls expressed that if they had a child with congenital defects, they had no confidence that they could bring up the child in this society. PMID- 8518433 TI - [Lifestyles related to preserving 20 or more teeth at 80 years of age]. AB - To explore lifestyle factors related to preserving 20 or more teeth at 80 years of age, a total of 114 Japanese persons aged 80 years old (70 with 20 teeth or more (mean teeth: 25.0 +/- 2.8) and 44 with 19 teeth or less (mean teeth: 5.2 +/- 6.3)) were studied. Study subjects received a dental examination and were directly interviewed, using a questionnaire, to collect such information as past episodes of tooth and gingival conditions, past attitude to dental care and several lifestyle habits. The following major findings emerged by statistical analysis. Probability of preserving 20 or more teeth at 80 years of age was significantly high with: (1) strict upbringing in childhood (p < 0.05 in males), (2) no swollen gums around 60 years old (p < 0.01 in males), (3) early visit to a dentist around 40 years old (p < 0.05 in males), and (4) not being fond of sweets in childhood (p < 0.05 in females). The following related to a high tendency toward preserving 20 or more teeth at 80 years of age: (1) graduate from primary school only (in females), (2) having a home dentist around 20 years old (in males), (3) tended to visit a dentist earlier at 20 years old (in males), (4) not eating sweet things at 60 years old (in males), and (5) have not smoked cigarettes (in males).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518434 TI - [Seasonal variation of sudden death based on analysis of death certificate information]. AB - Seasonal variation of sudden death (SD) was studied based on analysis of death certificates of all 8,519 SD patients, aged 15 years or older, who died during 1984 to 1986 in Niigata prefecture, Japan. SD was defined as death within 24 hours of onset of the underlying cause. SD showed a significantly high incidence during the cold season. When analyzed by underlying cause, the high incidence during cold season was shown for SD by circulatory diseases such as acute myocardial infarction (AMI; n = 1,446), other cardiovascular diseases (OCD; n = 4,375) and cerebrovascular accident (CVA; n = 1,725). However, no significant seasonal variation was observed for SD by non-circulatory diseases. By age group, the incidence of SD due to circulatory diseases was high during the cold season in the elderly (61 to 75 years) and the old age (76 years or older) groups, irrespective of kinds of the diseases, whereas the pattern varied by disease type in the young to middle age group (15 to 60 years). The highest incidence of SD due to AMI in the young to middle age group occurred in January with a second peak in July to August. Thus, not only low temperatures but high temperatures seemed to also contribute to the occurrence of SD by AMI in this age group. While SD due to OCD in this age group did not show a significant seasonal variation, that due to CVA showed a high incidence during cold season similar to the older age groups. These results suggest that factors affecting the occurrence of SD differed according to underlying cause and age of victims. PMID- 8518436 TI - [Study of several risk factors of ischemic heart disease in the last 17 years]. PMID- 8518435 TI - [Efficacy of hemoglobin-Alc, fructosamine, and 1,5-anhydroglucitol in community screening for diabetes mellitus]. AB - To evaluate the efficacy of hemoglobin-Alc, fructosamine, and 1,5-anhydroglucitol tests in screening for diabetes mellitus in communities, the sensitivity and the specificity of these tests were observed on the island of Ojika, Goto islands, Nagasaki prefecture Japan. A 75 gram glucose tolerance test was performed simultaneously on every participant, and WHO diabetes mellitus criteria were used to classify individuals. A total of 554 males and 820 females, older than 34 years, participated in the examination, representing a response rate of 42% and 52% respectively, and 86 were classified as diabetic. The sensitivity and the specificity of several screening levels were determined for each test. Each of the tests attained greater than 70% sensitivity and specificity simultaneously, but could not achieve greater than an 80% level simultaneously. If screening levels are selected for a sensitivity of as low as 50%, it is possible to produce a high specificity of 97-98%. These results provide valuable information for the planning of efficient diabetes mellitus detection programs in communities. PMID- 8518437 TI - [Factors contributing to food poisoning outbreaks in Japan]. PMID- 8518438 TI - Some factors affecting the oral rabies vaccination of free-ranging carnivores. AB - Conditions which affect the outcome of oral rabies vaccination programs include environmental factors, and the behaviour, population densities and dynamics of target and non-target species. Examples are given from recent research and the literature. PMID- 8518439 TI - Disease risks associated with wildlife translocation projects. AB - Translocation is defined as the movement of living organisms from one area for free release in another. Throughout the world, increasing numbers of native and exotic species are translocated every year. Most of these movements involve native mammals, birds and fish, and are made by private and national wildlife agencies to augment existing populations, usually for sporting purposes. The translocation of endangered species, often to reintroduce them into a part of the historical range from which they have been extirpated, has also become an important conservation technique. The success of potentially expensive, high profile wildlife translocation projects depends to a large extent on the care with which wildlife biologists and their veterinary advisers evaluate the suitability of the chosen release site, and on the ability of the translocated animals to colonise the area. The veterinary aspects of reintroduction projects are proving to be of extreme importance. There are already instances of inadequate disease risk assessment resulting in expensive failures and, worse still, the introduction of destructive pathogens into naive resident wildlife populations. In this paper, some of the disease risks attending wildlife translocation projects are described and suggestions are made for the development of systematic procedures to reduce these risks both at the source of the founder animals and at the proposed release site. PMID- 8518440 TI - Surveillance and control of anthrax and rabies in wild herbivores and carnivores in Namibia. AB - Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totalling 6,190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible. PMID- 8518441 TI - Reproduction of red foxes (Vulpes vulpes Linnaeus, 1758) in north-eastern Spain: a preliminary report. AB - Red fox reproduction in north-eastern Spain was studied by analysing the reproductive tracts of 84 females. Mean litter size was estimated to be 3.32 cubs per female, most of the births occurring from mid-March to mid-April. PMID- 8518442 TI - Prevalence of morbilliviruses among pinniped and cetacean species. AB - Since 1987, morbillivirus infections have caused serious disease outbreaks with high mortality among aquatic mammals. Baikal seals (Phoca sibirica) in Siberia were involved in an outbreak caused by a virus closely related to canine distemper virus (CDV) in 1987. Harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) in north-western Europe were struck by a newly recognised morbillivirus of seals (PDV1). A serological survey has indicated that these morbillivirus infections frequently occur among several pinniped species. Besides pinnipeds, the presence of morbillivirus infections among cetaceans, including whales, dolphins and porpoises, has been demonstrated since the outbreak of PDV among seals in north-western Europe. Morbillivirus was isolated from several stranded harbour porpoises (Phocoena phocoena). This virus proved to be very similar to a virus which was isolated during a disease outbreak with high mortality among striped dolphins (Stenella coeruleoalba) in the Mediterranean area. The viruses isolated from these cetacean species were quite different from the viruses isolated from the seals. They proved more related to the ruminant morbilliviruses, peste des petits ruminants virus and rinderpest virus. The potential transmission of the dolphin morbillivirus to the endangered population of the Mediterranean monk seal (Monachus monachus) has been considered. Studies are presently being conducted into the possibility of inducing protection against morbillivirus infection in this species by vaccination with an immune stimulating complex (ISCOM) preparation based on CDV. PMID- 8518443 TI - Epidemiology of contagious diseases, ecology of mammals, health, management and conservation biology: concluding remarks. AB - In conclusion to the Proceedings of the Symposium on the Health and management of free-ranging mammals (held in Nancy, France, in 1991), the author presents a review of the literature on the ecology of diseases of wild mammals. This discipline involves the ecology of both pathogens and hosts. The ecology of a pathogen may be considered as a synonym of epidemiology, i.e. the mode of transmission and circulation of parasites, their origin, invasion and persistence. The ecology of the host deals with the outcome of infection within different geographical and time scales: a) the impact on population density and communities within the time scale of the "observer" b) the effect of infection on the co-evolution of hosts and pathogens within the evolutionary time scale. This account is illustrated by numerous examples from field studies, as well as mathematical models, and concludes by examining the effect of pathogens on biodiversity, human health and the health of domestic animals. PMID- 8518444 TI - Home ranges of feral cats at Avonmouth Docks (United Kingdom). AB - The feral cat population at a 178 ha dockland site was studied for eighteen months using direct observation assisted by radio-tracking. Though food appeared to be abundant and widely distributed, the population density was low (10-15 adults/km2). Home ranges were similar for males and females, and were much smaller (15 +/- 17 ha and 10 +/- 7 ha, respectively) than would be expected from the low density. The implications of the findings for feral cat control were discussed, with particular emphasis on rabies emergency measures. PMID- 8518445 TI - Does myxomatosis still regulate numbers of rabbits (Oryctolagus cuniculus Linnaeus, 1758) in the United Kingdom? AB - Myxomatosis now kills a much smaller proportion of rabbit populations than in the past, while remaining an important regulatory factor, as shown experimentally. On two separate occasions, experimental reduction of the prevalence of the disease (by reducing infestations of the main vector, the rabbit flea) led to significant increases in numbers of rabbits surviving the winter. PMID- 8518446 TI - The impact of predators on livestock in the Abruzzo region of Italy. AB - Free-living populations of wolves (Canis lupus Linnaeus, 1758) and brown bears (Ursus arctos Linnaeus, 1758) regularly cause damage to livestock in the Abruzzo region of Italy. The laws of the region provide for compensation payments to owners for losses caused by predators. In the present paper, 4,993 validated claims made between 1980 and 1988 are examined. Losses ascribed to wolf, bear and wild boar attacks were 92.1%, 7.8% and 0.1%, respectively, of the total losses caused by predators during this period. The victims of wolf attacks were mostly sheep and goats (45.0%) and equids (38.5%), followed by cattle (16.4%) and rabbits, fowl and dogs (0.2%). Bears also principally attacked sheep and goats (67.6%), other targets being cattle (18.5%), equids (9.5%) and bee-hives (4.4%). A significant difference was observed between the number of attacks by wolves and bears; although both populations are of similar size. Other statistically significant differences have been observed between the periods in which the attacks take place on the different livestock and the predator species which reportedly caused the damage. Among cattle and equids, victims are mostly new born or young animals, while among sheep and goats only adult animals are attacked. PMID- 8518447 TI - The ecology of dogs and canine rabies: a selective review. AB - Although dogs are the most widespread and abundant of all carnivores, the role of the dog in human cultures and its impact on the environment have rarely been studied. These subjects are reviewed in the context of canine rabies. To understand the epizootiology of canine rabies, the ecology and population biology of the dog must be considered. Information on dog populations (in relation to different habitats, cultures, social strata of human populations and epizootiological situations) was collected in Nepal, Sri Lanka, Switzerland and Tunisia. In Switzerland (and Western Europe in general), rabies is maintained and spread by red foxes. The low prevalence of rabies in dogs may be explained by restrictive practices of dog-keeping and high rates of vaccination. In the other areas examined, dogs are poorly supervised and their population densities are high enough to support rabies, although it is questionable whether canine rabies exists independently of a wildlife reservoir. Dog-keeping practices, high rates of exposure and various cultural factors may lead to a high human rabies mortality rate. Nevertheless, dogs in these areas remain sufficiently accessible for vaccination and well-executed control programmes could prove successful. PMID- 8518448 TI - [Development of a factual model for the dynamics of the transmission of infection by the human immunodeficiency virus: an example for animal epidemiology]. AB - In order to simulate the spreading mechanism of human immunodeficiency virus (HIV), a factual approach was developed given the ease of incorporating new knowledge and taking into account the variability of a large number of sociological, biological and demographic factors, and also on account of the dynamics of the relational network of individuals. By way of example, the model was applied to data concerning homosexuals in San Francisco (United States of America) between 1980 and 1987, which enabled an evaluation to be made of the probability of HIV transmission from each partner, using two hypotheses about the evolution of contagiousness of an infected individual during the incubation period. An analysis of the sensitivity of the model revealed certain factors which had a strong influence on the growth of the epidemic. Application of this technique to the entire population of France is planned. PMID- 8518449 TI - Evaluation of a nematode (Capillaria hepatica Bancroft, 1893) as a control agent for populations of house mice (Mus musculus domesticus Schwartz and Schwartz, 1943). AB - Sudden, large-scale infestations of house mice (Mus musculus domesticus) occur irregularly in the cereal-growing regions of Australia, resulting in substantial economic losses. Mathematical modelling has been used to evaluate the use of the liver nematode Capillaria hepatica as a potential agent for the biological control of mouse populations. The models suggest that C. hepatica is unlikely to be successful as a single-release control agent: instead, the parasite would need to be released when it becomes apparent that an outbreak is likely. Stage structured models, including time delays and seasonal mouse demographic parameters, suggest that the parasite may be successful as a control agent, provided it can be introduced into the mouse population at least one year before an outbreak occurs. The optimum time for introduction is in summer or autumn. Some generalisations of this work are discussed. A parasite which affects fecundity alone is unlikely to be a good control agent, because it will destabilize the host population. Macroparasites may be unable to spread sufficiently rapidly to control sudden rises in vertebrate populations. PMID- 8518450 TI - Tactics for the control of wildlife rabies in Ontario (Canada). AB - Two different tactics are currently being utilized to control rabies in foxes, skunks and raccoons in Ontario, Canada. The first tactic, which involves live capturing with cage-traps and vaccinating by intramuscular injection, was successful in immunizing 54%-72% of the skunk and raccoon populations in a 60 km2 area of Toronto, Ontario. This area has been free of rabies for two-and-a-half years. The second tactic, involving the distribution of baits containing modified live-virus (ERA) rabies vaccine, was implemented to control rabies in foxes in both urban and rural areas of Ontario. In Toronto, 50% and 63% of the foxes were vaccinated during 1989 and 1990, respectively. Over the same period, 45% and 61% of the foxes in a 30,000 km2 area of south-eastern Ontario were immunized. Rabies is declining in both of these areas. A contingency plan has been devised to control an epizootic of raccoon rabies which is threatening to invade Ontario from the United States of America. PMID- 8518451 TI - A vaccinia-vectored rabies vaccine field trial: ante- and post-mortem biomarkers. AB - During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive. PMID- 8518452 TI - Design of insulin analogues for meal-related therapy. AB - The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and beta-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands (J Lab Clin Med 7:464-472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518453 TI - Circulating proinsulin-like molecules. AB - An improved understanding of the characteristics of proinsulin and its intermediate conversion products has resulted from the use of novel assays for distinguishing these molecules from insulin. Use of such assays may help clarify the role of insulin deficiency in non-insulin-dependent diabetes mellitus (NIDDM). Levels of proinsulin-like molecules are elevated in subjects who have NIDDM or impaired glucose tolerance. However, the observation that hyperproinsulinemia may occur in individuals without hyperglycemia suggests that elevated proinsulin levels may be a manifestation of beta-cell dysfunction rather than of increased demand on the beta cell. Although the metabolic effects of proinsulin-like molecules have yet to be elucidated, some studies indicate that the effect of these molecules on hepatocytes is greater than that on other insulin-sensitive cells. A potential therapeutic role of proinsulin in NIDDM thus has been envisioned, in that suppression of hepatic glucose output might reduce the risk of hypoglycemia caused by increased peripheral glucose uptake. Clinical study of proinsulin has been discontinued, however, owing to the finding of an association between use of human proinsulin and cardiovascular adverse events in one study. In NIDDM subjects, associations have been reported between elevated des 31,32 proinsulin concentrations and such cardiovascular risk factors as elevated blood pressure, increased serum triglyceride and total cholesterol values, and elevated plasminogen-activator inhibitor levels, suggesting a role of proinsulin in cardiovascular risk. Epidemiologic data, however, indicate that elevated levels of proinsulin-like molecules are related to low birth weight and that low birth weight is associated with increased risk of cardiovascular events, suggesting that inadequate intrauterine nutrition may be the common antecedent of augmented proinsulin levels and cardiovascular risk. PMID- 8518454 TI - The relationship of diabetes, loss of glucose-induced insulin secretion, and GLUT2. AB - Diabetes in humans and experimental animals invariably is associated with a loss of glucose-induced insulin secretion. It has been hypothesized that this reversible defect is an adaptation of beta cells to chronic hyperglycemia, a hypothesis that has been strengthened by studies in experimental models of diabetes. Recently, a marked underexpression of the beta-cell glucose transporter GLUT2 has been found in diabetic rodents. Although this finding provides an attractive potential explanation for the abnormal insulin secretion of diabetes, some problems with the hypothesis have emerged. Additional studies must be carried out to define the potentially pathogenic role of GLUT2. PMID- 8518455 TI - The molecular biology of glucose transport: relevance to insulin resistance and non-insulin-dependent diabetes mellitus. AB - The structure of the glucose transporter and the characteristics of the identified members of the facilitative glucose transporter gene family (GLUT1-5) are reviewed. The role of glucose transport in insulin resistance and non-insulin dependent diabetes mellitus (NIDDM) is discussed. The potential contributions of genetic mutation and disruption of short- or long-term regulation of glucose transporters, particularly GLUT4, in insulin-sensitive tissues to the etiology of NIDDM are examined. PMID- 8518456 TI - Molecular aspects of the etiology of type I diabetes mellitus. AB - Research into the molecular etiology of type I diabetes mellitus is ongoing in several promising areas. The goals of investigation include the identification of the genes responsible for susceptibility to or protection from disease and an enhanced understanding of the targets of the autoimmune response. Investigations into the process by which beta cells are destroyed suggest that diverse arms of the immune system are involved and that the autoimmune process is regulated. A model for predicting the time of development of type I diabetes in relatives of patients with diabetes, the reliability of which has permitted trials of preventive therapies to be designed and implemented, is discussed. PMID- 8518457 TI - Diabetes intervention therapy. AB - The involvement of autoreactive T cells in autoimmune diseases suggests the potential for intervention therapy in the setting of insulin-dependent diabetes mellitus. In the nonobese diabetic mouse, diabetes and insulitis have been inhibited by the modification of an amino acid in the major histocompatibility complex and by administration of anti-I-A antibody. T-cell vaccination has been shown to prevent autoimmune disease in animal models, and research is ongoing to develop monoclonal antibodies to a variety of T-cell receptor components. Strategies assessed in the clinical context include the administration of azathioprine, cyclosporine, and the antioxidant nicotinamide. Other potential strategies include the induction of specific oral tolerance, insulin prophylaxis, immunoenhancement therapy, and dietary manipulation. PMID- 8518458 TI - Prediction of persistent microalbuminuria in patients with diabetes mellitus. AB - Persistent microalbuminuria [albumin excretion rate (AER): 30-300 micrograms/min] is predictive of clinical nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and cardiovascular mortality in addition to nephropathy in patients with non-insulin-dependent diabetes. The clinical significance of intermittent microalbuminuria, however, is unknown. We performed serial measurements of urinary albumin excretion at intervals of approximately 6 months in 139 diabetic patients who at entry did not have persistent microalbuminuria to determine whether intermittent microalbuminuria occurs more frequently in those patients who subsequently develop persistent microalbuminuria. The relative risk for the development of persistent microalbuminuria in diabetic patients with a greater proportion than 3 out of 20 determinations in the microalbuminuric range was 17.4 (95% confidence interval, 3.92-77.2) in those with IDDM and 2.78 (0.99 7.8) in those with non-insulin-dependent diabetes when compared with matched diabetic patients with fewer elevated measurements. These data suggest that frequent intermittent microalbuminuria predicts the future development of persistent microalbuminuria particularly in IDDM patients and that AER should be assessed by serial rather than single measurements. PMID- 8518459 TI - Bimodality analysis of frequency distributions of 2-hour plasma glucose concentrations in the urban Micronesian population of Kiribati. AB - Bimodality in the frequency distribution of plasma glucose 2 h after a 75-g oral glucose challenge has been demonstrated in only a few population groups, and the generalizability of the phenomenon remains unclear. Therefore, we have studied the distribution of 2-h glucose in 1813 Micronesians, aged 20 years and over, from an urbanized community of the Pacific Ocean Republic of Kiribati. The 2-h plasma glucose distributions were consistent with a mixture model comprising two lognormal components for age groups 30-39, 40-49 and 50+ years. The parameters of the mixture distribution were estimated by the method of maximum likelihood. The prevalence of non-insulin-dependent diabetes mellitus was 7.3% as defined by World Health Organization diagnostic criteria, and 4.7% when defined according to age-specific optimal cut-off values based on the minimization of the total number of misclassified individuals. Assuming that the fitted mixture distribution for each age group was the true plasma glucose distribution, the sensitivity and specificity of the World Health Organization diagnostic criteria and the age specific optimal cut-off values were determined. Higher sensitivity with relatively little impairment of specificity resulted with the use of the former criteria. The prevalence of non-insulin-dependent diabetes mellitus increased with age as did the mean and standard deviation of the lower lognormal glucose component ("nondiabetics"). However, the mean and standard deviation of the "diabetic' upper component remained relatively constant and varied little with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518460 TI - Gas in the tissues--a complication of pelvic surgery in the subclinical diabetic patient. PMID- 8518461 TI - Molecular determinants of insulin action. AB - Insulin elicits an array of biologic responses. Insulin exerts a regulatory role in almost all cells of the body and is the primary hormone responsible for signaling the storage and utilization of basic nutrients. On the molecular level, the actions of insulin are initiated by binding of insulin to the insulin receptor. Interaction of the alpha and beta subunits of the receptor results in tyrosine kinase activity, which is integral to the initiation of cascades of phosphorylation/dephosphorylation reactions that mediate a large number of the actions of insulin. Insulin-receptor substrate 1 may be central to phosphorylation reactions through a role in serine and threonine kinase activity. Insulin action may also involve the generation of low-molecular-weight mediators capable of modulating intracellular enzymes. The regulation of glucose transport is a primary feature of the physiologic role of insulin and is performed by a family of glucose-transporter proteins with different characteristics. One mechanism by which insulin exerts its effect on glucose transport is the stimulation of the translocation of the glucose transporter to the plasma membrane. Degradation of insulin occurs through diverse mechanisms at numerous sites in the body. Reversal of the insulin signal at the cellular level may be accomplished by a class of enzymes termed phosphotyrosine phosphatases, which may play a role in certain pathophysiologic states. Important roles for insulin receptor kinase, glucose transporters, insulin-receptor substrate 1, and various intracellular enzymes in the actions of insulin have been demonstrated; nonetheless, the formulation of potential therapeutic strategies directed at particular stages of the insulin action cascade will require further elucidation of its components. PMID- 8518462 TI - Improving the cost-effectiveness of laparoscopic cholecystectomy. AB - The rapid shift from open to laparoscopic cholecystectomy has not been the result of carefully planned studies, but rather the result of pressure from patients to undergo the new procedure in order to avoid the pain from a traditional incision. In order for laparoscopic cholecystectomy to prove cost effective, there must be a low complication rate, the cost of discretionary equipment must be considered, and the role of routine cholangiography seriously questioned. PMID- 8518463 TI - Is laparoscopic herniorrhaphy an effective alternative to open hernia repair? AB - While the inguinal approach to hernia repair remains the standard of care, laparoscopic hernia repair techniques are rapidly evolving. The first 102 laparoscopic hernia repairs were reviewed. Reported herein are the types of hernias repaired, length of hospital stay, early recurrence rate, complications, and assessment of postoperative pain. The long-term recurrence rate has yet to be determined. From these results, it is felt that in select patients, laparoscopic hernia repair is an effective surgical alternative in the treatment of inguinal hernia. PMID- 8518464 TI - A comparison of laparoscopic and traditional appendectomy. AB - Forty-one serially performed laparoscopic appendectomies were compared to 41 randomly selected traditional open appendectomies performed during the same 18 month period. The average age and sex distribution of the two groups were similar. The pathological diagnoses of acute appendicitis and perforation were similar in both groups. The complication rates were not statistically different in the two groups. There were no complications unique to the laparoscopic group. The hospital stay was considerably shorter for patients undergoing laparoscopic appendectomy (p < .05). Statistical significance was found both in patients with and without perforation. PMID- 8518465 TI - Pleural empyema: early pulmonary decortication and lung biopsy. AB - Presented herein is a case of a patient with infectious acute pneumopathy who developed exudative pleural effusions. A diagnostic and therapeutic thoracoscopy was carried out. The usefulness of this method in early pulmonary decortication is emphasized. PMID- 8518466 TI - Laparoscopic varicocele repair. AB - Varicocele is a common condition for which currently accepted methods of treatment are less than satisfactory. Reported herein is a successful laparoscopic technique of repair. PMID- 8518467 TI - Laparoscopic diagnosis and treatment of Meckel's diverticulum complicated by gastrointestinal bleeding. AB - Laparoscopy has been utilized for many gynecological and surgical procedures that previously required laparotomy. Its use in the diagnosis and treatment of Meckel's diverticulum complicated by gastrointestinal bleeding is described. PMID- 8518468 TI - Endoscopic removal of an infarcted appendix epiploica. AB - Infarction of an appendix epiploica is a rare event that is seldom diagnosed preoperatively. Report herein is a case of a 76-year-old male complaining of abdominal pain. The etiology of this pain was unclear but the diagnosis of epiploitis was preoperatively suspected. The infarcted epiploic appendix was identified and resected laparoscopically. PMID- 8518469 TI - Double gallbladder treated successfully by laparoscopy. AB - A rare case of true duplication of the gallbladder is herein reported on a young male patient with other congenital abnormalities. Both gallbladders had unequivocal signs of chronic inflammatory disease and lithiasis. The patient was diagnosed preoperatively as having acute cholecystitis but the diagnosis of an accessory gallbladder was made only at the time of surgery. Emphasis is placed on the use of a complete cholangiographic evaluation before proceeding with the operation in order to prevent inadvertent damage to the biliary ductal system. The accessory gallbladder must then be removed to avoid an unnecessary reoperation. All of this can be accomplished readily by laparoscopic surgery. PMID- 8518470 TI - Persistent trophoblastic implants after salpingostomy for ectopic pregnancy. AB - Laparoscopic management of ectopic pregnancies is the accepted method of treatment in most centers. This report describes a case of persistent trophoblastic implants to the peritoneum after laparoscopic linear salpingostomy for evacuation of an early ectopic pregnancy. Based on this experience, methods for follow up after such procedures, and recommendations for management of persistent trophoblastic implants are discussed. PMID- 8518471 TI - Laparoscopic partial cystectomy for vesical endometrioma. AB - A case of endometriosis is presented involving the urinary bladder successfully treated by laparoscopic partial cystectomy. The laparoscopic surgical technique is fully discussed. Laparoscopic partial cystectomy represents a viable option in the treatment of vesical endometriosis, obviating the need for a formal laparotomy. PMID- 8518472 TI - Laparoscopic resection of a splenic artery aneurysm. AB - Laparoscopic resection of a 2.5 cm splenic artery aneurysm in a 64-year-old woman is presented. The diagnosis was suspected on plain roentgenograms of the lumbosacral spine and confirmed by abdominal CT scan and selective splenic arteriography. The hospital course was uneventful and she was discharged 2 days postoperatively. This new endoscopic approach offers a useful alternative to the surgical management of splenic artery aneurysms, and may have some theoretical advantages, including less postoperative pain and shorter convalescence. PMID- 8518473 TI - Small bowel obstruction secondary to incarcerated Richter's hernia from laparoscopic hernia repair. AB - Presented herein is a case of a patient who, during a laparoscopic herniorrhaphy, developed profound bradycardia upon introduction of the pneumoperitoneum. Following discharge, the patient presented 24 h later with herniation through the trocar port incision. With laparoscopic surgery being used more frequently, there will be an increase in the incidence of these types of complications; however, with better awareness, they may be avoided. PMID- 8518474 TI - Thoracoscopic dissection of the esophagus in human cadavers. AB - A technique for thoracoscopic dissection of the esophagus is described which gives a large and magnified view of the pleural cavity, the mediastinum, and the esophagus. This technique was developed on human cadavers which gives excellent technical resources for learning and practicing endoscopic surgical anatomy of the esophagus. It avoids the need to change the position of the patient to perform a total thoracoabdominal esophagectomy via a triple surgical approach. PMID- 8518475 TI - Reduction of postoperative adhesions to Marlex mesh using experimental adhesion barriers in rats. AB - Polypropylene mesh (Marlex) is commonly used to reinforce the abdominal wall during hernia repair. Recently, hernia repair has been performed using laparoscopic techniques. Marlex used for reinforcement is placed directly onto the peritoneum (i.e. transperitoneal) in some repairs. This practice of placing Marlex mesh directly onto the peritoneum may, however, lead to clinically significant bowel adhesions. This study tests whether three different adhesion barriers (Gore-Tex, Interceed, and poloxamer) can reduce bowel adhesion formation when placed directly over the fixed Marlex mesh in the rat. Interceed and poloxamer significantly reduced adhesion formation to Marlex mesh. Gore-Tex had the greatest amount of adhesion formation but this was not significantly different from Marlex control. Poloxamer treatment appeared to significantly reduce tensile strength and Marlex mesh incorporation. The Interceed treatment also appeared to reduce tensile strength as compared to Marlex alone, however, this difference was not significant. The use of Marlex mesh with an Interceed barrier reduces intraabdominal adhesions while not reducing the tensile strength of the Marlex mesh incorporation. PMID- 8518476 TI - Laparoscopically assisted implantation of ventriculoperitoneal shunts. AB - Laparoscopically-assisted minimally invasive procedures have been applied to a broad spectrum of abdominal interventions. Neurosurgeons performing ventriculoperitoneal shunt operations for hydrocephalus used to place the peritoneal catheter by performing an upper abdominal midline or subcostal incision. In this report, to reduce the patient's inconvenience caused by the laparotomy wound, three consecutive ventriculoperitoneal shunts were implanted, assisted by laparoscopy. By means of three incisions (one 10 mm supraumbilical for the camera and two 5 mm in the right hypochondric region for instrumentation) the peritoneal catheter was placed next to the epiploic foramen. After subcutaneous pull-through of the catheter to the right supraclavicular region, the operation was continued by the neurosurgeon. The postoperative course was uneventful in all cases. The patients were dismissed 3-7 days after surgery. Short time follow-up (212, 202, and 169 days after surgery) showed no complications and perfect function of the ventriculoperitoneal shunts. PMID- 8518477 TI - Techniques for the simultaneous management of incarcerated ventral herniae and cholelithiasis via laparoscopy. AB - Two patients presented with symptomatic cholelithiasis and cholecystitis and ventral herniae. In Case 1, an incarcerated supraumbilical hernia was present in a morbidity obese patient. In Case 2, an incarcerated incisional hernia was present. Both patients underwent laparoscopic cholecystectomy and simultaneous herniorrhaphy. Technical details of the operative technique are presented. PMID- 8518478 TI - The cost-effectiveness of laparoscopic appendectomy. AB - The first 26 attempted laparoscopic appendectomies for the clinical diagnosis of acute appendicitis were compared with an age and sex matched control group of patients randomly selected from those operated on for acute appendicitis during the previous 6 month period. Both groups were comparable in terms of severity of disease, absolute white count, previous surgery, and co-morbidity. The mean operative time for the laparoscopic appendectomy group was 73 min vs 36 min for the open group (p < 0.001), but the morbidity (12% vs 38%) was significantly less (p < 0.01). The length of stay was shorter (2.8 vs 3.4 days) but this failed to achieve statistical significance. The time to full recovery was significantly (p < 0.01) shorter (11.1 vs 23.7 days). Hospital charges for laparoscopic appendectomy were higher (but not significantly) than for open appendectomy. The results of this study confirm that laparoscopic appendectomy is a safe and effective alternative to open appendectomy which results in a more rapid return to full activity but incurs higher hospital charges. The overall cost effectiveness of laparoscopic appendectomy should be even greater than that of open appendectomy. PMID- 8518479 TI - Receptivity is a polarity dependent special function of hormonally regulated uterine epithelial cells. AB - Useful knowledge of the mechanisms which regulate ovoreceptivity and implantation remains elusive in spite of increasing efforts to apply the technology of biochemistry and to a lesser extent, cellular and molecular biology to the analysis of the problem. Existing models used to analyze interactions of the blastocyst and endometrial cells of the uterus have been unable to account for nongenotypic embryonic losses, particularly those following in vitro fertilization and embryo transfer. Separation of endometrial uterine epithelial (UE) and uterine stromal (US) cells was used to demonstrate that each cell type responds independently and interdependently to the same regulatory signals. Cultured by classical techniques UE cells proved unable to respond to steroid hormone signals. For this reason UE cell cultures could not be used to develop an experimental cell system that mimicked growth and development of UE cells in utero. The failure of classical UE cell cultures derived from their inability to maintain epithelial cell polarity. Polarity, the spatial asymmetry of plasma membrane domains, is intrinsic to the structure and function of an epithelial cell. Apical and basolateral surfaces have different lipid and protein compositions which are correlates of the special functions of that epithelial cell. As epithelial cells differentiate they must, in response to regulatory cues, direct the flux of membrane components moving into and out of each surface in order to establish the polarity characteristic of each stage specific expression. The acquisition of receptivity by the apical surface of the UE cell may be considered to be such a special function. To prove this hypothesis polarized cultures of primary UE cells had to be developed that were hormonally responsive. Such an experimental cell system could serve as a model for in vitro implantation. This essay describes such a culture system in which blastocysts cocultured with UE cells in the presence of estrogen, will as predicted, fail to attach. This polarized UE cell system provides a functional in vitro model to study ovoreceptivity. It is now feasible to initiate studies of hormonal regulation of the composition and function of UE cell plasma membranes as they reflect the nonreceptive, receptive, and refractory nature of its apical surface. PMID- 8518480 TI - Mullerian inhibiting substance: new perspectives and future directions. AB - MIS, as a differentiate and antiproliferative agent, is precisely regulated, for example, at the transcriptional level by such transacting factors as SRY, and posttranslationally by testosterone. Processing of MIS most likely requires an as yet unknown in vivo protease which probably serves to control cleavage of MIS and hence its activation at specific sites wherein a localized program of cell death is initiated via a receptor mediated event. Progress has been made in understanding the molecular domains of MIS; current efforts are focused on characterizing the wild type MIS receptor as well as cloning and expressing the MIS receptor. We need now to understand how to target and efficiently activate MIS at its projected site of action. We must focus, after structural analysis of its receptor, on elucidating the MIS initiated intracellular signals which result in localized cell inhibition. Understanding of these mechanisms will permit design of antitumor agents and therapeutic strategies. Similarly, understanding regulation of MIS expression may lead to therapeutic induction of expression in those states where depressed expression is associated with tumorigenesis, sexual ambiguity, or infertility. PMID- 8518481 TI - Characteristics of uterine aging. AB - Uterine aging is in part responsible for a decline in fecundity which begins in middle age in most mammals. Characteristics of uteri from a variety of animals in middle age and old age are reviewed and the factors which may be responsible for this decline discussed. These include age-related changes in the hypothalamus, pituitary, and ovaries; loss of number or function of steroid hormone receptors; morphological changes in the uterine epithelium; the accumulation of collagen fibrils in the uterine stroma; and loss or impairment of the decidual response. The ultrastructural morphology of uterine epithelial, stromal, and decidual tissue from 4 month old and 18 month old Fischer 344 rats is presented and compared. PMID- 8518482 TI - The study of partially ordered 1 1/2 0 alloys by HREM. PMID- 8518483 TI - Papers from the Joint Meeting of the Dutch and Belgian Societies for Electron Microscopy and the Belgian Society for Cell Biology. Antwerp, December 10-11, 1992. PMID- 8518484 TI - A new software package for interpreting electron diffraction contrast images of arbitrary displacement fields: SIMCON. PMID- 8518485 TI - Quantitative analysis of the porous structure of a petroleum reservoir. PMID- 8518486 TI - Combined scanning near field optical and force microscopy. PMID- 8518487 TI - Concrete-pathology-secondary precipitations. PMID- 8518488 TI - In-situ HVEM study of dopant dependent (113)-defect generation in silicon during 1-MeV electron irradiation. PMID- 8518489 TI - Disorder in Al-Mn-Fe icosahedral alloys introduced by iron. PMID- 8518490 TI - Internal calibration technique for HREM studies of nanoscale particles. PMID- 8518491 TI - Ultrastructure of the normal menstrual cycle: a review. PMID- 8518492 TI - Essential hypertension: a perspective. PMID- 8518493 TI - What's in a name? PMID- 8518494 TI - The determination of blood pressure. PMID- 8518495 TI - Blood pressure variability and the renal response. PMID- 8518496 TI - Protecting the kidney in hypertension. PMID- 8518497 TI - Practical approach to hypertension in children and adolescents. PMID- 8518498 TI - Hypertension in pregnancy. PMID- 8518499 TI - Hypertension in the elderly. AB - Hypertension and its cardiovascular consequences are growing medical problems in the elderly. Hypertension in older patients is characterized not only by an increase in peripheral vascular resistance, but also by a reduction in arterial compliance. These abnormalities result in marked rises in systolic pressures and variable diastolic pressures that range from markedly elevated to low-normal. Several large placebo-controlled trials have recently demonstrated that treating hypertension in elderly patients reduces cardiovascular disease. This is true in patients with systolic and diastolic hypertension as well as patients with isolated systolic hypertension. Although reduction of cardiovascular end points has only been demonstrated for thiazide diuretics and beta-blockers, it may be reasonable to include other classes of medications in the initial treatment of some elderly hypertension patients. PMID- 8518500 TI - Hypertension and left ventricular hypertrophy: what is the link? PMID- 8518501 TI - Liquorice: new insights into mineralocorticoid and glucocorticoid hypertension. PMID- 8518502 TI - Antihypertensive therapy: a look ahead. PMID- 8518503 TI - Hypertension among Rhode Island adults. PMID- 8518504 TI - Lantibiotics--unusually modified bacteriocin-like peptides from gram-positive bacteria. AB - Lantibiotics are antibacterial peptides frequently produced by Gram-positive bacteria. They are distinguished by unique structural properties unprecedented so far in peptide chemistry. The most striking feature is the occurrence of intramolecular rings introduced by the thioether amino acids lanthionine and 3 methyllantionine. Additional usual amino acids such as didehydroalanine and didehydrobutyrine are found. Lantibiotics are produced from ribosomally synthesized prepeptides and the unusual amino acids are formed by post translational modifications. This review summarizes the current knowledge on the biosynthetic mechanisms and enzymes taking part in biosynthesis, on the primary and spatial structures of the active peptides and the correlation between structural aspects and the antibacterial activity. Furthermore, the mode of action of type-A lantibiotics and the immunity phenomenon are described, and an outlook for future research and potential applications is given. PMID- 8518505 TI - Complement activation and sensitizing antibodies in Lyme borreliosis. A microbial adherence immobilization assay for Borrelia burgdorferi (MAIA-BB). AB - A report is presented about the capability of complement to directly clump Borrelia burgdorferi. The new phenomenon which has been termed "microbial adherence", is either antibody-independent or requires the presence of "sensitizing" antibodies depending the strains tested. Microbial adherence is associated with immobilization and killing of borrelias. A microbial adherence immobilization assay for B. burgdorferi (MAIA-BB) was developed to detect sensitizing antibodies in patients with Lyme borreliosis and in B. burgdorferi infected animals. PMID- 8518506 TI - Comparative activities of macrolide derivatives on murine listeriosis. AB - The new macrolide derivatives such as clarithromycin, roxithromycin and azithromycin have only slightly stronger in vitro antibacterial activity on Listeria monocytogenes than the older derivatives such as erythromycin and spiramycin. In vivo, however, the new macrolides exert a much better therapeutic action on murine listeriosis. Among the new derivatives, clarithromycin is the most active. Azithromycin has one characteristic advantage: it is still active several days after cessation of therapy because of its long half-life. This strong therapeutic activity may be due to the known intracellular accumulation of macrolides in macrophages, which is essential for the eradication of intracellular bacteria such as L. monocytogenes. In spite of the strong intracellular accumulation the effector function of the defense system is not impaired, because the course of infection with a macrolide-resistant strain of L. monocytogenes in mice was not enhanced by macrolide treatment. PMID- 8518507 TI - Anti-HBs antibody kinetics--a 4-year follow-up after hepatitis B vaccination. AB - To describe anti-HBs kinetics after hepatitis B vaccination, a logarithmic function was established using anti-HBs determinations in sera drawn from 97 to 147 vaccinees at 5 times during a 4 year follow-up period. A comparison with 2 published mathematical models showed that the logarithmic formula was less complex, and computed values correlated better with real anti-HBs titres. PMID- 8518508 TI - Adenovirus isolations from patients with conjunctivitis in Thuringia. AB - 57 adenoviruses (AV's) isolated from 1979 through 1986 from about 200 patients with (kerato) conjunctivitis were identified as AV8, 7, 3, 17/H29, 9, 2, and 10, in decreasing order. DNA restriction analysis with 5 enzymes revealed the three strains of the intermediate 17/H29 strains to be identical. The same conclusion was reached for the two AV9 strains, but the latter differed from the AV9 prototype in two enzymes. Restriction site alterations were physically mapped for 3 enzymes and for an AV8 variant differing in HindIII. PMID- 8518509 TI - Studies of the prevalence of Coxiella burnetii, the agent of Q fever, in the foothills of the southern Bavarian Forest, Germany. AB - In studies carried out in 1991 in the foothills of the southern part of the Bavarian Forest, in the district of Freyung/Grafenau, ticks and small mammals were collected and examined for the presence of Coxiella (C.) burnetii and sera of small mammals and cattle investigated for antibodies against this rickettsia. A total of 1716 imagines and nymphs of Ixodes ricinus were collected by flagging and 892 larvae and nymphs of the same tick species removed from small mammals. In addition to 1095 serum samples from cattle, 326 specimens of nine species of small terrestrian mammals were examined. Neither in ticks nor in rodents, C. burnetii was detected, however, in 17 of 21 localities, seropositive cattle were found. Altogether, 12% of all 1095 heads of cattle tested were seropositive for C. burnetii antibodies. These serological results indicated a wide dissemination of C. burnetii in cattle of the region investigated, but there was no indication of a natural focus. As in other areas of Europe, an independent natural cycle of the agent involving cattle only is assumed to occur in this region. PMID- 8518510 TI - Chemotaxonomy and molecular taxonomy of some coryneform clinical isolates. AB - Six reference strains of the genus Brevibacterium as well as fifteen clinical isolates tentatively assigned to the genus using conventional biochemical methods, were the subject of chemotaxonomic and DNA similarity studies. Five of these clinical isolates were assigned either to the genera Aureobacterium, Mycobacterium, Gordona or to Rhodococcus on the basis of their DNA mol% G+C, mycolic acid, amino-acid, sugar and menaquinone contents. Among the ten remaining strains, six were not brevibacteria and only four conformed to the description of the genus Brevibacterium sensu stricto. These strains showed low values of DNA relatedness with Brevibacterium epidermidis ATCC 35514T and Brevibacterium linens ATCC 9174, and could only be described as Brevibacterium spp. The results indicate that studies of chemical markers are essential for the correct identification of brevibacteria. PMID- 8518511 TI - Identification of mycobacterial isolates by thin-layer and capillary gas-liquid chromatography under diagnostic routine conditions. AB - The mycolic acid patterns of 75 strains of mycobacteria belonging to 46 different species were studied by thin-layer chromatography (TLC). Additionally, the mycolic acid pyrolytic cleavage products were determined by capillary gas-liquid chromatography (C-GLC). Eleven different patterns based on number, type and Rf values of the detected lipid spots were identified. The mycolic acid methyl ester profiles of clinical isolates were compared with those of reference strains. In this way, it was possible to relate these clinical isolates to mycobacterial groups defined by their mycolic acid profiles. The 11 patterns and the methods used are described in detail. PMID- 8518513 TI - A method for typing Listeria monocytogenes strains by classification of listeriocins and phage receptors. AB - A method for typing Listeria monocytogenes (L.m.) strains was developed which is based on two different approaches. First, strains were classified according to the phage receptors specific to their mitomycin-induced prophages. The frequency of lysogenic strains ranged between 63 and 80%, depending on the serotype. For non-lysogenic strains, a reversed phage-receptor analysis was applied based on the susceptibility of the strains to be typed against bacteriophages from selected, inducible indicator strains. As a second method, typing of mitomycin induced listeriocins was shown to be practicable as well. By this approach, it was possible to distinguish 11 different listeriocins when using a set of 7 selected indicator strains. Only two of these listeriocins were probably produced by L.m. strains of serotype 4b. A combination of the two approaches described raises the number of types. When applied to 20 human isolates of L.m. belonging to serotype 4b, 17 different types were demonstrated. 46 L.m. strains of serotype 1/2b could be differentiated into 38 types of which 18 clinical isolates represented 17 different types. 26 L.m. strains of serotype 1/2a isolated from various food products showed a large heterogeneity, with 22 different types. The power of discrimination of the method outlined recommends its application in epidemiological investigations. PMID- 8518512 TI - Serodiagnosis of tuberculosis. Evaluation of a sulpholipid antigen. AB - In order to evaluate the suitability of serology in the diagnosis of tuberculosis the Mycobacterium tuberculosis anti-sulpholipidic IV IgG were assayed, using the ELISA test, in 41 healthy controls, 121 hospitalized but non-tuberculous patients and 142 tuberculous persons including 46 cured patients. At the 150 and 300 O.D. thresholds proposed in previous studies using the same antigen, the specificity was 88.27% and 98.76%, respectively, and the sensitivity 25% and 11.45%. These results were not related to different potential factors (age, background, associated pathology) but to infection intensity which enhanced the IgG reaction. This may explain discrepancies observed in previous studies made under other epidemiological conditions. Therefore, in this European population from a universitarity hospital, it appears that too many tuberculous patients have such a low IgG reaction that serology cannot be an effective assay in the diagnostic step. PMID- 8518514 TI - Evaluation of the efficacy of different antibiotics in inhibiting colonisation of Vibrio cholerae O1 in the rabbit intestine. AB - The efficacy of ciprofloxacin, norfloxacin and tetracycline in prevention of colonisation of V. cholerae O1 in the rabbit intestine were tested. V. cholerae O1 highly colonised the gut of rabbits which did not receive any antibiotic. All antibiotics tested inhibited the colonisation of V. cholerae O1 within the rabbit intestine. Moreover, ciprofloxacin and norfloxacin were found to be as effective as tetracycline suggesting that these drugs should be subjected to clinical trials for the treatment of cholera in comparison with tetracycline. PMID- 8518515 TI - Binding of Escherichia coli to Penrose rubber drains--an in vitro study. AB - Ten different isolates of Escherichia coli were used to compare bacterial attachment to Penrose rubber drains at different temperatures and to investigate a possible relation with cell surface hydrophobicity and charges, as well as the capacity of autoaggregation. Penrose rubber drain pieces of 1 cm2 were incubated with 4.8 x 10(6) E. coli cells for 1 h at 22, 37 and 42 degrees C, respectively. After rinsing with phosphate buffered saline (PBS), the number of adhering bacteria on the drain pieces was calculated by measuring cellular ATP (adenosine triphosphate) bioluminescence. Bacterial cell surface properties at different temperatures were determined by two-phase partitioning and autoaggregation was determined by arbitrary scoring under the dissecting microscope. For most strains of E. coli, the number of adherence to Penrose rubber drain was higher at 22 degrees C than at 37 degrees C and 42 degrees C. Bacterial cell-surface properties and autoaggregation capacity were influenced by the growth temperature, but without correlation to bacterial ability to attach to rubber drains. Thus, the present study demonstrates that attachment of E. coli to Penrose rubber drains was significantly influenced by temperature, but bacterial cell-surface hydrophobicity and charge as well as autoaggregation capacity had no influence on bacterial attachment ability. PMID- 8518516 TI - Molecular investigation of clinical Enterococcus faecium isolates highly resistant to gentamicin. AB - Over a 10-month period, 22 beta-lactamase negative E. faecium strains resistant to ampicillin were isolated from severely compromised hospitalized patients. Most isolates were clinically significant. Twenty of these strains were also resistant to extraordinarily high levels of gentamicin, a finding described rarely in E. faecium. By whole-cell DNA restriction endonuclease digestion, the 20 strains with both ampicillin and high-level gentamicin resistance segregated into only 3 different groups, suggesting introduction of limited clones into this population of patients. Plasmid DNA profiles and plasmid DNA restriction enzyme analysis supported this grouping for 18 of these 20 strains, the two remaining isolates had slightly different profiles. Both strains lacking high-level gentamicin resistance had clearly different molecular profiles. The results of hybridization experiments strongly suggested the presence of a similar genetic determinant of high-level gentamicin resistance in E. faecalis and E. faecium. High-level gentamicin resistance in E. faecium was shown to be transferable on conjugative plasmids, so that further dissemination of this resistance trait may be anticipated. Our data indicate that the use of a nucleic acid probe is a promising diagnostic tool for screening both E. faecium and E. faecalis for high level gentamicin resistance. PMID- 8518517 TI - Weight to length ratio--a good parameter for determining nutritional status in preterm and full-term newborns. AB - To identify which parameter showed the strongest correlation with neonatal body fat store, when the ratios for assessing both weight-for-length and the mid-arm circumference to head circumference (MAC/HC) were included in the analysis, body anthropometrics and skinfold thickness were measured in 250 full-term and 125 preterm infants. Among the study cases, 66.7% were appropriate for gestational age, 26.7% were small for gestational age and 6.7% were large for gestational age. Sum of the skinfold thickness measured at the midtricepital and subscapular areas correlated well with body anthropometrics, weight/length ratio, body mass index, ponderal index and mid-arm circumference to head circumference ratio. Multiple stepwise regression analysis revealed that the weight/length ratio correlated best with skinfold thickness in both full-term and preterm newborn infants. Therefore, the simple weight/length ratio might be useful for evaluation of the nutritional status of intrauterine growth, and in the prediction of metabolic complications in both full-term and preterm newborns with abnormal intrauterine growth. PMID- 8518518 TI - Efficacy of low-dose dopamine infusion. AB - Urine output following administration of a low-dose dopamine infusion was assessed in 20 very immature infants (median gestational age 27 weeks). Prior to the infusion, all infants had had a period of anuria. Urine output improved significantly during the second 24 h after commencing the infusion but, at that time period, urine output was greater than 2 ml/kg/h (designated a good response) in only 13 infants. There was no significant difference in gestational age, birth weight, period of anuria or fluid input of infants who had a good or a poor response to dopamine. Although the baseline blood pressure did not differ significantly between these two groups, the increase in blood pressure resulting from dopamine administration was significantly greater in those infants with a good response in urine output (p < 0.02). We conclude that low-dose dopamine infusion can improve urine output in very immature infants. Our results suggest that there may be inter-individual variation in the sensitivity to dopamine. PMID- 8518519 TI - Longitudinal follow-up of growth in children born small for gestational age. AB - Postnatal growth was followed in a population-based group of 123 small-for gestational-age (SGA, birth weight < -2 SD) children (66 boys and 57 girls) to four years of age in order to determine the incidence and time of catch-up growth. Gestational age was determined by ultrasound in gestational weeks 16-17 in all pregnancies, thus eliminating the problem of distinguishing between SGA and preterm infants. Infants with well-defined causes for slow growth rate, i.e. those infants with chromosomal disorders, severe malformations, intrauterine viral infections or cerebral palsy, were excluded. The boys showed an extremely fast weight catch-up, 85% of them reaching weights greater than -2 SD at the age of three months and remaining above this level to the end of the study period. Such a fast catch-up growth was observed in only two-thirds of the girls, but at four years of age 85% of the girls were also above -2 SD. Length catch-up was more gradual than weight catch-up. Of the boys, 54% had lengths below -2 SD at birth, 26% at 1 year of age, 22% at 2 years of age, 17% at 2.5 years of age and 11% (n = 8) at 4 years of age. Corresponding figures for girls were: 69% at birth, 28% at 1 year, 15% at 2 years, 12% at 2.5 years and 5% (n = 3) at 4 years. At 4 years of age, only six boys and three girls remained below -2 SD for both weight and height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518520 TI - Prediction of height achievement at five years of age in children born very preterm or with very low birth weight: continuation of catch-up growth after two years of age. AB - To predict height at five years in a cohort of 565 very preterm and/or very low birth-weight children, hypothesized growth determinants were subjected to discriminant analysis. Many neonatal parameters were not significantly associated with short stature at five years of age. A correct classification of stature (smaller/larger than the 10th percentile at five years of age) could be obtained in 85% of children, using the following variables: height at two years of age; total (or mid) parental height; parental level of education; length at one year of age; hypertension during pregnancy; sex; weight at two years of age; length percentile at one year of age. However, when compared to actual longitudinal data, the false-positive rate was 37%. The survey also demonstrated the continuing catch-up growth in very preterm and very low-birth-weight infants after two years of age. PMID- 8518522 TI - Gender difference in aerobic capacity in adolescents after cure from malignant disease in childhood. AB - The aim of this study was to document gender difference in aerobic capacity after cure from malignant disease in childhood. We studied 18 males and 17 females aged 11-19 years and 10-18 years, respectively. They had all completed their treatment at least two years previously. Twelve males and 11 females received anthracyclines in comparable doses (range 150-500 mg/m2). Maximal exercise tests were performed on a cycle ergometer. Maximal oxygen consumption (ml/min/kg) was significantly (p < 0.001) lower only in females when compared to their controls. We postulate two causes: girls are smaller than their controls, possibly related to their higher vulnerability to cranial irradiation than boys; and girls were less involved than boys in sports. The influence of anthracycline treatment on aerobic capacity was only observed in males and not in females. This could be related to the higher exercise level in boys than in girls. PMID- 8518521 TI - Neurological manifestations of hemorrhagic colitis in the outbreak of Escherichia coli O157:H7 infection in Japan. AB - An outbreak of hemorrhagic colitis associated with Escherichia coli O157:H7 occurred in a kindergarten in Saitama, Japan from September to November, 1990. Seven patients admitted to our hospital showed neurological manifestations: generalized seizures, impaired consciousness, urinary incontinence, gaze nystagmus, phrenic nerve palsy, action tremor and vertigo. Two patients died. On the basis of the clinical courses and laboratory findings of the seven patients and postmortem findings of one case, these neurological symptoms were suspected to be induced by the verotoxin elaborated by Escherichia coli O157:H7. PMID- 8518523 TI - Renal effects of cyclosporin A in children treated for idiopathic nephrotic syndrome. AB - Little data have been published on tubular renal function during cyclosporin A treatment in children without transplants. We studied 12 young subjects (mean age 10 years) with steroid-responsive idiopathic nephrotic syndrome and with signs of steroid toxicity. After achieving remission with prednisone 60 mg/m2, 8 children started cyclosporin A therapy (6 mg/kg/day) (group A) and 4 children were given cyclophosphamide 2.5 mg/kg/day (group B). The latter were considered as controls together with 10 other children with idiopathic nephrotic syndrome in complete remission and off therapy (group C). We monitored creatinine clearance and tubular handling of beta 2-microglobulin, sodium, phosphorus and uric acid for one year. Cyclosporin A induced a decrease in creatinine clearance with a decrease in fractional excretion of beta 2-microglobulin; sodium excretion was similar in the two treated groups and a transient decrease in fractional excretion of uric acid was seen only in patients receiving cyclosporin A. Both groups showed an increased renal threshold phosphate concentration. Our results suggest that in children, cyclosporin A therapy induces a decrease in glomerular filtration rate associated with increased reabsorption activity of proximal tubular cells. PMID- 8518524 TI - Follow-up in patients with aspartylglucosaminuria. Part I. The course of intellectual functions. AB - Progressive mental retardation is the main clinical symptom in aspartylglucosaminuria. The intellectual functions of 116 patients were studied. Based on cross-sectional test results, an average longitudinal developmental profile consisted of three parts: a period of abnormally slow but positive development in childhood, a gradual loss of reached skills after the age of 13-16 years and a rapid decline after the age of 25-28 years. Only nine young patients had a developmental age higher than six years, and two higher than seven years. The mean age of the female group was seven years higher than that of the males, but the mean developmental ages were the same for both groups. PMID- 8518525 TI - Dietary changes in Swedish adolescents. AB - A school-based dietary survey, using seven-day records, was performed in two cohorts of Swedish adolescents; 14- and 17-year-olds. The study comprised 366 boys and 365 girls. When compared to previous studies in Sweden, a striking finding was a decrease in dietary fat intake and an increase in carbohydrate intake. However, the relative intake of saturated fat had not changed (15% of total energy). The dietary change was mainly due to an increased consumption of cereal products. There were no major differences in dietary habits or nutrient density of the food between the two age groups, or between boys and girls. The mean intakes of protein, fat and carbohydrate, expressed as a percentage of the total energy intake, were 15, 33 and 52%, respectively. The mean intakes of vitamins and minerals were low only for selenium. The boys had a high iron intake (1.5 and 1.7 times the recommended intake for 14- and 17-year-olds, respectively) while the mean iron intake for girls was 0.9 times the recommended dietary allowances in both age groups. The intake of dietary salt was higher in boys than in girls (7.7 g and 9.0 g per day in 14- and 17-year-old boys, respectively, and 5.8 g per day in both 14- and 17-year-old girls). In a long-term health perspective, this positive change in nutrient intake in adolescents may contribute to a reduction in the incidence of diet-related diseases in Sweden.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518526 TI - The pressure pain threshold (PPT) of certain muscles in children suffering from recurrent abdominal pain of non-organic origin. An algometric study. AB - The origin of recurrent abdominal pain of "non-organic origin" is believed to be psychogenic in most cases. But the pathogenesis of the pain itself is unknown. To test the hypothesis that recurrent abdominal pain of non-organic origin is related to increased pain sensitivity in the myofascial elements of the abdominal wall itself, an investigation of pain pressure threshold of the abdominal wall, close to the umbilicus, was carried out. Altogether 140 children in the fourth school grade, approximately 11 years old, were tested for pressure pain threshold. Two groups were constituted: one without pain symptoms (no recurrent abdominal pain, chest pains or headache (n = 50)) and one with recurrent abdominal pain (n = 49). The pressure pain threshold differed significantly (p < 0.0001). To support the hypothesis that recurrent abdominal pain is a part phenomenon of a specific pattern of muscular tension and tenderness, the pressure pain threshold was tested in five other muscles, with significant results. PMID- 8518527 TI - The covariation of common psychosomatic symptoms among children from socio economically differing residential areas. An epidemiological study. AB - Psychosomatic symptoms among children are believed to be commonplace. In this investigation by questionnaire, 47% of 1333 schoolchildren reported one or several symptoms, such as recurrent abdominal pain, headache, chest pains, loss of appetite and disturbances in bowel function. Coexistence of such symptoms was considerable and if a child had one of these, the probability that it would have one or more other symptoms was significantly increased. This correlation may strengthen both the suspicion that these symptoms are often psychosomatic and the idea that they have common CNS origin. There were appreciable differences in the frequency of the symptoms, between children at the more socially stable schools and schools with social problems. In the latter, the frequencies of symptoms differed between Swedish and immigrant children, which was not the case in the more socially stable schools. PMID- 8518528 TI - Peritoneal dialysis in the very low-birth-weight neonate (less than 1000 g). PMID- 8518529 TI - Cardiac tamponade in a preterm neonate secondary to a chest tube. AB - In a preterm infant, chest tubes were inserted for treatment of bilateral pneumothoraces. Hemorrhagic pericardial effusion with cardiac tamponade developed, probably resulting from traumatic injury by the left chest tube. The infant survived due to timely diagnostic and therapeutic intervention. No recurrence of pericardial effusion was seen and follow-up showed normal psychomotor development. PMID- 8518530 TI - Transient erythroblastopenia of childhood presenting with echovirus 11 infection. AB - We report a case of transient erythroblastopenia in a three-year-old girl presenting with echovirus 11 infection. Viral infection was demonstrated by isolation of echovirus 11 in stool cultures and the presence of echovirus 11 specific IgM antibody in serum. We suggest that echovirus may have played a role in the pathogenesis of transient erythroblastopenia of childhood in this patient. PMID- 8518531 TI - Heparin-induced thrombocytopenia in children. AB - Two children aged 3 months and 14 years developed heparin-induced thrombocytopenia whilst receiving heparin. The clinical course was complicated by renal vein thrombosis in the 3-month-old infant and subcutaneous haemorrhage requiring resuscitation in the 14-year-old child. Anticoagulant therapy was discontinued immediately in the 3-month-old child. In the 14-year-old child, because of the need for continued anticoagulation therapy, low molecular weight heparin was used until warfarin could be substituted. PMID- 8518532 TI - Acute renal failure complicating diabetic ketoacidosis. AB - Two previously healthy children, aged 13 and 14 years, respectively, presented with diabetic ketoacidosis. Both children developed acute renal failure, a rare complication of diabetic ketoacidosis and required dialysis. PMID- 8518533 TI - Neuronal migrational disorders: diffuse cortical dysplasia or the "double cortex" syndrome. AB - We report a 10-year-old girl who presented with a single episode of partial complex seizure. Neurological examination and psychological evaluation were normal. Electroencephalogram showed abnormalities in the left temporo-occipital region. Magnetic resonance imaging revealed a bilateral layer of tissue iso intense with gray matter, between the wall of the lateral ventricle and the cortex, extending from the frontal to the occipital region, and enlarged left lateral ventricle. The images indicated diffuse cortical dysplasia, also known as band heterotopia or "double cortex", and left cortical hemiatrophy. PMID- 8518534 TI - A hereditary form of pseudohypoaldosteronism may be manifested in the course of pyelonephritis. PMID- 8518535 TI - Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy. AB - Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capillaries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra- and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focus on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucose-induced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of extracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level. PMID- 8518536 TI - ACE inhibitors and diabetic nephropathy: clinical and experimental findings. AB - Apart from near normal metabolic control, early treatment of an increase in blood pressure in diabetic patients with nephropathy, is one of the most important therapeutic methods to prevent further progression of this complication. Long term studies, recently published, suggest that ACE inhibitors have a beneficial effect on albuminuria and progression of nephropathy, irrespective of their hemodynamic effects. However, the mechanism by which ACE inhibitors exert these positive effects on glomerular pathology is still unclear. Several non hemodynamic factors have been identified as being involved in the pathogenesis of diabetic nephropathy: (a) changes in the composition of glomerular basement membrane due to a changed metabolism of the proteins which make up this structure; consequences are an impairment of the filtration properties, onset of proteinuria as well as thickening of basement membrane; (b) Mesangial expansion due to an overproduction of mesangial matrix and deposition of proteins as well as (c) impairment of mesangial clearance function; consequences are development of glomerulosclerosis and reduction of filtration surface. It is known that the renin-angiotensin-system is stimulated in diabetic patients with nephropathy and that angiotensin II influences the synthesis of glomerular and mesangial proteins as well as the function of mesangial cells. Hypothetically, these points could explain the beneficial effects of ACE-inhibitors on the progression of diabetic nephropathy. PMID- 8518537 TI - The cardiac renin-angiotensin system: physiological relevance and pharmacological modulation. AB - Many cell types in myocardial tissue, including cardiocytes, contain receptors for angiotensin-II, but the activation of these receptors requires angiotensin concentrations in the micromolar range, which do not occur in plasma in vivo. However, angiotensins formed locally in the heart can activate these receptors in a paracrine and autocrine mode. In cardiac hypertrophy due to hemodynamic overload, the myocardial angiotensin formation is enhanced due to an augmented expression of angiotensinogen and ACE. Though the mRNA for prorenin is expressed in myocardium, the formation of active renin within the heart has not yet been demonstrated and myocardial renin activity is mainly due to contamination from circulating active renin. Intracoronary application of ACE inhibitors in hypertrophied hearts in vivo and in vitro indicates that the locally formed angiotensin-II contributes to coronary constriction, impairment of diastolic relaxation and marginally to the maintenance of systolic tension development. Angiotensin-II can exert trophic effects on cardiocytes and cardiac fibroblasts, and chronic inhibition of the cardiac RAS by ACE-inhibitors or AT receptor antagonists can induce partial regression of overload hypertrophy, even without normalizing the overload. This anti-trophic action may be partially due to the impairment of the angiotensin axis, but also due to enhancement of bradykinin availability, which results in an augmented release of endothelial anti-trophic signals such as EDRF/NO and prostacyclin. Preliminary evidence is compatible with the hypothesis that an activated local RAS in elastic arteries contributes to the localization and progression of atherosclerosis by suppressing EDRF releasability. However, the anti-atherosclerotic potential of ACE inhibitors and AT receptor antagonists in humans is still unknown. PMID- 8518538 TI - Renin-angiotensin system components and endothelial proteins as markers of diabetic microvascular disease. AB - Endothelial cell damage, which is associated with local thrombin formation and inflammation, can lead to the release of endothelium-synthesized factors into plasma, such as vWFAg, TM, ACE and ET-1. These markers of endothelial damage are increased in some patients with diabetes mellitus, but the differences with normal are often small and not closely correlated with the severity of microvascular disease, as judged from the degree of albuminuria and the severity of retinopathy. Prorenin, which may also be related to abnormal endothelial cell function or endothelial damage, is elevated in many patients with diabetes, both type I and II, and its level is more closely correlated with the severity of microvascular disease. It is already elevated at an early stage. Further studies will reveal whether, in diabetes, an increased plasma prorenin is a reliable predictor of progressive microvascular disease. It is even conceivable that prorenin is not only a marker of diabetic microvascular disease but also has a role in its pathogenesis, via local proteolytic or non-proteolytic prorenin activation. PMID- 8518539 TI - Renin-angiotensin system and myocardial collagen matrix remodeling in hypertensive heart disease: in vivo and in vitro studies on collagen matrix regulation. AB - The interstitial space of the myocardium is composed of nonmyocyte cells and a highly organized collagen network which serves to maintain the architecture and mechanical behavior of the myocardial walls. It is the myocardial collagen matrix that determines myocardial stiffness in the normal and structurally remodeled myocardium. In hypertensive heart disease, the heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for collagen synthesis and degradation, explains the appearance of diastolic and/or systolic dysfunction of the left ventricle that leads to symptomatic heart failure. Several lines of evidence suggest that circulating and myocardial renin-angiotensin systems (RAS) are involved in the regulation of the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In cultured adult rat cardiac fibroblasts angiotensin II was shown to directly stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation, that would lead to collagen accumulation. In the spontaneously hypertensive rat, an appropriate experimental model for primary hypertension in man, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness due to interstitial fibrosis could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease. PMID- 8518540 TI - Coronary microcirculation in hypertensive heart disease: functional significance and therapeutic implications. AB - In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. This leads to an impairment of diastolic function of the left ventricle and coronary flow reserve despite normal epicardial arteries. Consequently, antihypertensive treatment should aim at [13] reversing myocyte hypertrophy, [14] restoring myocardial structure and [8] improving coronary flow reserve along with blood pressure normalization. PMID- 8518541 TI - Functional changes in left ventricular hypertrophy: diagnosis of impaired diastolic function in patients with hypertension. AB - Left ventricular hypertrophy is usually associated with impaired left ventricular diastolic function which can be characterised by an altered pressure volume relationship. Since diastolic flow velocities are closely related to the difference in pressure between the left atrium and left ventricle, parameters of diastolic function can be determined by Doppler echocardiography. However, the pressure difference is additionally influenced by factors which have no relation to left ventricular diastolic function. These include preload, afterload, inotropy, heart rate and left ventricular systolic function. Despite these limitations, Doppler echocardiography is a valuable tool to diagnose therapeutic effects on diastolic function in patients with left ventricular hypertrophy. PMID- 8518542 TI - The renin-angiotensin system and extracellular matrix. AB - A hallmark of vascular disease is the inappropriate proliferative and synthetic behaviour of vascular smooth muscle cells. This phenotypically immature behaviour arises as a consequence of the myocytes undergoing phenotypic conversion and/or clonal proliferation of a "fetal" type of smooth muscle cell preexisting in the vessel wall. De-differentiation and initiation of proliferation is not only induced by endothelial desquamation and acute exposure of smooth muscle cells to platelet-derived mitogens, but also occurs in the uninjured blood vessel. Therefore normal components of the blood vessel are implicit in the pathological process. These include vasoconstrictor peptides, growth factor peptides and extracellular matrix molecules. In vitro and in vivo experimentation has indicated that while some of these compounds individually are only mild stimulators of smooth muscle proliferative metabolism, they may act synergistically to induce robust responses. Here we discuss the effects of the vasoconstrictor peptide angiotensin II, which can be locally generated within the vessel wall itself, on the expression of extracellular matrix molecules in vitro and in vivo. We focus on the angiotensin II-modulated expression of extracellular matrix glycoproteins, e.g. thrombospondin, tenascin, fibronectin and laminin. PMID- 8518543 TI - Exposure assessment for power frequency electric and magnetic fields (EMF) and its application to epidemiologic studies. AB - Epidemiologic studies suggesting possible health effects associated with exposure to electric and magnetic fields (EMF) from the transmission, distribution, and use of electricity have motivated increased interest in and attention to EMF exposure assessment. The result has been new instruments, measurement approaches, and exposure models that can improve on what has been a weakness in past epidemiologic studies, namely EMF exposure assessment. This paper presents a status report on EMF exposure assessment that emphasizes the need for incorporation of these advances in future studies. Several factors are identified that make the assignment of contemporary or retrospective EMF exposures potentially more difficult than for other environmental agents. These include: EMF is not generally detectable by humans, exposure scenarios for EMF are generally not memorable, there is no clear mechanism for EMF effects, and the pervasive nature of EMF in an industrialized society makes identification of a low-exposure group difficult. Elements of study design that are impacted by the nature of EMF exposures include: sampling and measurement strategies, summary measures of exposure, and the choice of surrogate and/or models of exposure. Consideration of these exposure assessment issues and incorporation of recent advances can improve the overall quality of epidemiologic studies with an EMF exposure component. PMID- 8518545 TI - Estimating fish consumption rates for Ontario Amerindians. AB - The routine assessment of human exposure to contaminants requires that exposure via consumption of freshwater fish be considered because many chemicals persist and/or bioaccumulate in fish. Estimates of fish consumption rate were determined for Ontario Amerindians from data on the concentration of mercury in the hair of 4,327 Amerindians residing in 58 reserves across the province, combined with data on mercury concentrations in three commonly consumed species of fish collected from lakes surrounding these reserves. Estimated rates of fish consumption were found to differ between sexes, with males consuming a geometric mean of 19 g of fish per day, while females were estimated to consume a geometric mean of 14 g/day. Fish consumption rate was found to increase with increasing latitude, a surrogate measure of community isolation, and to increase with age. Seasonal variation was also noted, with fish consumption rates being highest during summer months and lowest in winter. These data may provide regulatory agencies with a more statistically representative basis upon which to establish assumptions concerning fish consumption rates for risk assessment purposes. Factors such as the location of the exposed population, age and sex of exposed individuals, and time of year in which an assessment is being conducted, should also be considered as specific situations require. PMID- 8518544 TI - Health effects of tropospheric ozone: review of recent research findings and their implications to ambient air quality standards. AB - The U.S. Environmental Protection Agency (EPA) Administrator proposed (on August 3, 1992) to retain the current National Ambient Air Quality Standard (NAAQS) for ozone (O3) on the basis of data assembled in a draft Criteria Document (1986) and its Addendum (1988) which, together with a draft Staff Paper (1988), received public comment and review comments by the EPA's Clean Air Scientific Advisory Committee (CASAC). This paper summarizes and discusses research findings presented since 1988 which, based on the author's experience as a Chairman of CASAC, are most relevant to the promulgation of a primary (health based) NAAQS for O3. These newer findings include substantial evidence from controlled chamber exposure studies and field studies in natural settings that the current NAAQS contains no margin of safety against short-term effects that the EPA has considered to be adverse. They also include evidence from epidemiologic studies that current ambient exposures are associated with reduced baseline lung function, exacerbation of asthma and premature mortality, as well as evidence from chronic animal exposure studies at concentrations within current ambient peak levels that indicate progressive and persistent lung function and structural abnormalities. The current NAAQS, if retained, may therefore also be inadequate to protect the public from effects resulting from chronic exposure to O3. PMID- 8518546 TI - A portable datalogger to evaluate recall-based time-use measures. AB - Self-completed recall diaries have become a common tool in epidemiology and exposure assessment to determine the location and/or activities of subjects during study periods. Unfortunately, little effort has been made to determine the accuracy of such an approach for providing information without significant bias. It is usually assumed that subjects are truthful and complete in their recall. An electronic datalogger has been designed to allow subjects to record location changes as they occur in real time. Subjects carried the datalogger for 3-5 days and completed recall diaries at the end of each day. The concordance between the two records was found to be relatively good for the most commonly visited locations, e.g., bed/bath, workplace, etc. Poorer agreement was found for locations of short or infrequent visits, e.g., cellar or vehicle. The merits and shortcomings of the datalogger approach are discussed. While having external validation for recall diary records is clearly necessary, reliance on subject input to the datalogger presents its own problems related to subject compliance. Electronic approaches which do not require active subject input are recommended to aid in the evaluation of recall diaries. PMID- 8518547 TI - A linear model relating breath concentrations to environmental exposures: application to a chamber study of four volunteers exposed to volatile organic chemicals. AB - A linear model relating levels of volatile organic chemicals (VOCs) in exhaled breath to personal exposures at environmental (parts per billion) levels has been developed and evaluated in a chamber study of four human volunteers. The purpose of the model is to allow estimation of VOC concentrations in the body from measurements of exposure, or conversely to estimate previous exposure from a measurement of exhaled breath. The model differs from previous models in considering long-term inhalation at low or moderate concentrations rather than instantaneous intake (as in drug administration) or intermittent exposure at high concentrations (as in occupational situations). The model is based on a mass balance approach using one or more compartments to represent distribution of the chemical in the body. The main observable parameters in the model are the residence times tau 1 in the compartments, their "capacities" Ai, and the fraction f of the parent compound that is exhaled under equilibrium conditions. The basic equations for the one-, two-, three-, and n-compartment cases are derived. Solutions to these equations for the cases of a sudden constant high exposure, a sudden constant low exposure, and a linearly increasing exposure are provided. These solutions can be readily applied to more complex exposure scenarios. The chamber study suggests residence times on the order of a few minutes in the blood and 1-2 hr in the vessel-rich group of tissues. The design of the chamber study did not allow an estimate of the model parameters for fat; a subsequent chamber study has provided initial estimates of 50-100 hr. Field studies of personal exposures and breath concentrations of several hundred persons suggest values of f ranging from 0.1 for xylenes and ethylbenzene to about 0.9 for tetrachloroethylene. PMID- 8518548 TI - Proliferation and morphology of melanoma cells and benign human melanocytes under varying culture conditions. AB - In order to enable a direct comparison of gene expression in human melanoma cells and in normal human melanocytes, culture conditions were investigated under which both cell populations can be grown in vitro. Five of 13 melanoma cell lines tested could be cultured to confluence in a melanocyte medium containing fetal calf serum, 12-O-tetradecanoylphorbol-13-acetate and stimulators of cyclic adenosine monophosphate, whereas none could be grown to confluence in a serum free hormone-supplemented melanocyte medium containing basic fibroblast growth factor and other mitogens. In both melanocyte media the melanoma cells showed signs of increased morphological differentiation with dendrite formation. Normal human melanocytes could be grown in melanoma cell medium for a few days, after which the cultured cells showed a less differentiated phenotype. Since morphological changes may reflect variations in gene expression, we suggest that comparative studies on gene expression of benign and malignant melanocytes should also include thorough investigation under identical culture conditions. PMID- 8518549 TI - A consideration of ambient solar ultraviolet radiation in the interpretation of studies of the aetiology of melanoma. AB - Values of ambient solar ultraviolet radiation and estimated hourly radiation for both erythemal (UVB) and UVA radiation are presented for the latitudes where the major studies of human cutaneous melanoma have been performed; 50-55 degrees N (Denmark and Western Canada), 30-34 degrees S (Western Australia) and 15-27 degrees N (Queensland). Comparisons are made for exposure patterns relating to constant and to intermittent exposure, and combinations of these. The results show that the wavelength distribution of solar ultraviolet radiation varies with latitude and exposure pattern. At higher latitudes, the contribution of exposure at peak periods is more marked. The comparison or combination or results from epidemiological studies at different locations will be aided by this consideration of the variation in different aspects of solar radiation, and tables are given for this purpose. PMID- 8518550 TI - Effect of Toremifene in patients with metastatic melanoma: a phase II study of the EORTC Melanoma Cooperative Group. AB - The EORTC Melanoma Cooperative Group conducted a phase II trial (study number 18891) to study the effect of Toremifene in 45 patients with advanced, metastatic melanoma. Male and female patients, median age 61 (range 23-88) years received a mean total dose of 11 g (4.3-62.6) orally for at least 6 weeks. No objective remissions were seen. Four patients (3 women and 1 man; 9%) experienced 3-6 months' disease stabilization. The toxicity of the drug, given at a dose of 240 mg daily, was negligible. Because of the minimal side-effects, Toremifene may be recommended for patients who have only a small number of slowly growing metastases, in particular to soft tissue and lung. PMID- 8518551 TI - Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen. AB - Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution. PMID- 8518552 TI - Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. AB - Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10 27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518553 TI - From adhesion to signalling: roles of integrins in the biology of human melanoma. AB - Integrins are cell surface heterodimers which act as regulators of adhesion and as signal transducers in normal and neoplastic cells. The expression and function of integrins are subject to change during the neoplastic transformation of melanocytes and the progression of melanoma. The integrin profile of human melanoma is also characterized by marked inter- and intratumour heterogeneity. These processes influence the interaction of melanoma cells with extracellular matrix (ECM) components and with other cell types that express integrin ligands. Integrins on melanoma cells not only act as mediators of adhesive interactions but also act as signalling molecules. The signal transducing function of integrins plays a role in a number of biological responses of melanoma cells to ECM-derived stimuli, including production of proteolytic enzymes, invasion of basement membranes, expression of genes and proliferation. PMID- 8518554 TI - An S receptor kinase gene in self-compatible Brassica napus has a 1-bp deletion. AB - S locus glycoprotein (SLG) and S locus receptor kinase (SRK) cDNAs were isolated from an S allele present in a number of self-compatible Brassica napus lines. This A10 allele did not segregate with self-incompatibility in crosses involving other self-incompatible B. napus lines. The SLG-A10 cDNA was found to contain an intact open reading frame and was predicted to encode an SLG protein with sequence similarities to those previously associated with phenotypically strong self-incompatibility reactions. SLG-A10 transcripts were detected in the developing stigma at steady state levels even higher than those detected for SLG alleles linked with self-incompatibility. Analysis of the corresponding SRK-A10 cDNA showed that it was very similar to other S locus receptor kinase genes and was expressed predominantly in the stigma. However, a 1-bp deletion was detected in the SRK gene toward the 3' end of the SLG homology domain. This deletion would lead to premature termination of translation and the production of a truncated SRK protein. The A10 allele was determined to represent a B. oleracea S allele based on its segregation pattern with the B. oleracea S24 allele when both these alleles were present in the same B. napus background. These results suggest that a functional SRK gene is required for Brassica self-incompatibility. PMID- 8518555 TI - Developmental and age-related processes that influence the longevity and senescence of photosynthetic tissues in arabidopsis. AB - Factors that influence the longevity and senescence of photosynthetic tissues of Arabidopsis were investigated. To determine the influence of reproductive development on the timing of somatic tissue senescence, the longevity of rosette leaves of the Landsberg erecta strain and of isogenic mutant lines in which flowering is delayed (co-2) or sterile flowers are produced (ms1-1) were compared. No difference in the timing of senescence of individual leaves was observed between these lines, indicating that somatic tissue longevity is not governed by reproductive development in this species. To examine the role of differential gene expression in the process of leaf senescence, cDNA clones representing genes that are differentially expressed in senescing tissues were isolated. Sequence analysis of one such clone indicated homology to previously cloned cysteine proteinases, which is consistent with a role for the product of this gene in nitrogen salvage. RNA gel blot analysis revealed that increased expression of senescence-associated genes is preceded by declines in photosynthesis and in the expression of photosynthesis-associated genes. A model is presented in which it is postulated that leaf senescence is triggered by age related declines in photosynthetic processes. PMID- 8518556 TI - Carboxy-terminal deletion analysis of oat phytochrome A reveals the presence of separate domains required for structure and biological activity. AB - A series of seven carboxy-terminal deletion mutants of oat phytochrome A were stably expressed in transgenic tobacco to localize phytochrome domains involved in chromophore attachment, spectral integrity, photoreversibility between the red light (Pr)- and far-red light (Pfr)-absorbing forms, dimerization, and biological activity. Amino acids necessary for chromophore attachment in vivo were localized to the amino-terminal 398 residues because mutant proteins this small had covalently bound chromophore. Deletion mutants from the carboxy terminus to residue 653 were spectrally indistinguishable from the full-length chromoprotein. In contrast, further truncation to residue 399 resulted in a chromoprotein with a bleached Pfr absorbance spectrum, Pr and Pfr absorbance maxima shifted toward shorter wavelengths, and reduced Pfr to Pr phototransformation efficiency. Thus, residues between 399 ad 652 are required for spectral integrity but are not essential for chromophore attachment. The sequence(s) between residues 919 and 1093 appears to be necessary for dimerization. Carboxy-terminal mutants containing this region behaved as dimers under nondenaturing conditions in vitro, whereas truncations without this region behaved as monomers. None of the plants expressing high levels of deletion mutants lacking the 35 carboxy-terminal amino acids displayed the light-exaggerated phenotype characteristic of plants expressing biologically active phytochrome A, even when the truncated phytochromes were expressed at levels 6- to 15-fold greater than that effective for the full-length chromoprotein. Collectively, these data show that the phytochrome protein contains several separable carboxy-terminal domains required for structure/function and identify a domain within 35 residues of the carboxy terminus that is critical for the biological activity of the photoreceptor in vivo. PMID- 8518557 TI - Analysis of a tobacco mosaic virus strain capable of overcoming N gene-mediated resistance. AB - The genome of Ob, a tobamovirus that overcomes the N gene-mediated hypersensitive response (HR), was cloned as a cDNA, and its nucleotide sequence was determined. The genomic organization of Ob is similar to that of other tobamoviruses, consisting of 6506 nucleotides and containing at least four open reading frames. These open reading frames encode a 126-kD polypeptide with a 183-kD readthrough product, a 30.6-kD movement protein, and an 18-kD coat protein. A bacteriophage T7 promoter sequence was fused to the full-length cDNA clone to obtain infectious RNA transcripts. These transcripts, when inoculated onto tobacco plants, induced disease symptoms indistinguishable from plants inoculated with Ob viral RNA. To determine which viral factor is responsible for the resistance-breaking character of Ob, a recombinant virus was constructed in which the movement protein gene of tobacco mosaic virus was replaced with that of Ob. Cultivar Xanthi NN tobacco plants infected with this virus responded with an HR, indicating that the Ob movement protein alone does not act to overcome the N gene-mediated response. Following mutagenesis of the infectious Ob cDNA clone with hydroxylamine, populations of transcripts from the mutagenized DNA were inoculated onto Xanthi NN tobacco, and a variant that induced the HR was identified. The mutant was analyzed and found to contain a single nucleotide change in the 126-kD gene. Recreating the mutation in the Ob cDNA clone by site-directed mutagenesis resulted in a virus that caused symptoms identical to the chemically induced mutant. PMID- 8518558 TI - Determination of the functional elements within the vacuolar targeting signal of barley lectin. AB - We have previously demonstrated that the carboxyl-terminal propeptide of barley lectin is both necessary and sufficient for protein sorting to the plant vacuole. Specific mutations were constructed to determine which amino acid residues or secondary structural determinants of the carboxyl-terminal propeptide affect proper protein sorting. We have found that no consensus sequence or common structural determinants are required for proper sorting of barley lectin to the vacuole. However, our analysis demonstrated the importance of hydrophobic residues in vacuolar targeting. In addition, at least three exposed amino acid residues are necessary for efficient sorting. Sorting was disrupted by the addition of two glycine residues at the carboxyl-terminal end of the targeting signal or by the translocation of the glycan to the carboxy terminus of the propeptide. These results suggest that some components of the sorting apparatus interact with the carboxy terminus of the propeptide. PMID- 8518559 TI - Expression and purification of the epidermal growth factor receptor extracellular domain utilizing a polycistronic expression system. AB - High level expression of the epidermal growth factor receptor ectodomain (EGFR ED) has been achieved using a polycistronic expression system. The expression vector was designed such that EGFR-ED was at the 5' end of a tricistron followed by luciferase and dihydrofolate reductase (dhfr). Following transfection into Chinese hamster ovary cells, clones were isolated under selective conditions for dhfr expression and monitored for luciferase activity and EGFR-ED expression using immunofluorescence microscopy. A 100-kDa protein corresponding to EGFR-ED was efficiently secreted from expressing cells. Two purification schemes were used to obtain protein at least 95% pure. Glutaraldehyde crosslinking was used to show that EGFR-ED specifically binds EGF and TGF alpha and that the affinity for EGF is 5.5 x 10(-7) M. PMID- 8518560 TI - Overexpression of the Bacillus subtilis and circulans xylanases in Escherichia coli. AB - An efficient expression system for a low-molecular mass xylanase in Escherichia coli has been developed. A gene encoding the mature Bacillus circulans (Bc) xylanase was designed to imitate the frequency of degenerate codons used in E. coli. Appropriate degenerate codons were used to create multiple unique restriction sites for future mutagenesis studies. The synthetic gene was constructed in two stages, both involving ligation of overlapping oligonucleotides. The synthetic Bc gene was then converted to a Bacillus subtilis (Bs) xylanase gene via a single codon substitution (Thr147Ser). The plasmids containing both synthetic genes were further modified for the direct expression in E. coli. Under the control of the lac promoter, recombinant xylanase has been produced at levels as high as 300 mg/liter in soluble form in the cytoplasm. This efficiency represented a dramatic improvement over all previous attempts involving the expression of the natural genes, with the xylanase being secreted in those cases. Characterization of our gene products indicated that the purified recombinant product was correctly processed and enzymatically active. PMID- 8518561 TI - Chemical synthesis, molecular cloning, overexpression, and site-directed mutagenesis of the gene coding for pumpkin (Curcubita maxima) trypsin inhibitor CMTI-V. AB - The gene encoding for a pumpkin (Curcubita maxima) trypsin inhibitor CMTI-V was synthesized chemically. The synthetic gene was prepared from four overlapping oligonucleotides by overlapping extension. The synthetic gene was amplified by polymerase chain reaction, cloned into a T7 expression vector and expressed in Escherichia coli as a fusion protein. The clone, namely 70-1, encoded a fusion protein containing 7 amino acid residues of the N-terminus of the bacterial protein rho 10 and the entire 68 residues of CMTI-V. The wild-type fusion protein constituted approximately 15% of the total bacterial protein mass and was purified to homogeneity in a single step by antibody affinity chromatography. The wild-type fusion protein possesses inhibitory activity toward trypsin and beta Factor XIIa, but to a lesser extent when compared to the natural CMTI-V. A mutant, T43A, in which threonine at position 43 (P2 position) was replaced by alanine, was constructed. This mutant showed considerably lower specific inhibitory activity toward both trypsin and beta-Factor XIIa. PMID- 8518562 TI - High-level production of the mouse epidermal growth factor in a Bacillus brevis expression system. AB - In order to determine the three-dimensional structure, the folding pathways, and the residues which are critical for biological functions of the mouse epidermal growth factor (mEGF), large amounts of wild-type and site-specific mutants are needed for biological and physiochemical studies. Genes coding for mEGF and its mutants were expressed in a Bacillus brevis system in which the expressed foreign proteins were secreted into the culture medium. However, proteases were also secreted that resulted in partial degradation of the desired foreign proteins. One mutant with much less protease secretion was isolated by applying nitrosoguanidine mutagenesis on a B. brevis strain. A new vector to facilitate DNA mutagenesis and sequencing was also constructed for this system. Methodologies for the transformation of B. brevis and the purification of expressed mEGF were developed. Under the optimized conditions, the production of the mEGF and its mutants was about 50 mg per liter, and yielded up to 10 mg of purified mEGF. Several mEGF mutants have been produced and their receptor binding abilities have been measured. PMID- 8518563 TI - Expression, purification and characterization of multigram amounts of a recombinant hybrid HV1-HV2 hirudin variant expressed in Saccharomyces cerevisiae. AB - Hirudin (HIR), derived from leeches, and tick anticoagulant peptide (TAP) are polypeptide protease inhibitors of thrombin and coagulation factor Xa (fXa), respectively, and they have both shown utility in vitro and in vivo as potent antithrombotic agents. A thorough side-by-side comparison of the in vivo efficacy of factor Xa inhibition compared to thrombin inhibition by TAP and HIR, respectively, required purification and characterization of multigram amounts of hirudin. Therefore, a recombinant Saccharomyces cerevisiae strain was developed using a plasmid containing the gene encoding the MF alpha 1 preproleader, a synthetic hybrid HV1-HV2 HIR gene, and a galactose-inducible promoter which directed the secretion of 44 mg/liter of recombinant HIR (rHIR) after induction. rHIR was purified by a process that consisted of two chromatographic steps and decolorization. Total yield for the purification process was 3.6 g, or 41%. This process gave 59-fold purification of rHIR that was judged to be > 96% pure with regard to polypeptide content by capillary zonal electrophoresis and reversed phase high-performance liquid chromatography. Single, unique N- and C-termini were obtained by sequencing and were identical to those predicted from the deduced sequence of the cDNA. Determination of the dissociation constant, by thrombin:hirudin inhibition reaction, and anticoagulant activity, by the activated partial thromboplastin time, demonstrated that the hybrid rHIR HV1-HV2 protein discussed in this report was essentially equipotent with rHIR preparations HV1 and HV2 reported by others. PMID- 8518564 TI - Annual reports of directors of public health. PMID- 8518565 TI - Nicotine patches in general practice. PMID- 8518566 TI - Overpopulation and overconsumption. PMID- 8518567 TI - Pre-employment chest radiography and NHS staff. PMID- 8518568 TI - Vertically transmitted HIV infection in the British Isles. AB - OBJECTIVE: To describe the epidemiology of vertically acquired HIV infection in the British Isles, the level of underreporting, the vertical transmission rate, and clinical spectrum of paediatric AIDS. DESIGN: Confidential, linked registers based on reporting from obstetricians and paediatricians; anonymous unlinked neonatal HIV serosurveys. SETTING: British Isles. SUBJECTS: Children born to mothers with HIV infection. MAIN OUTCOME MEASURES: Trends in HIV infection and vertical transmission rate. RESULTS: In Scotland and the Irish Republic, where most maternal HIV infection is related to drug misuse, the annual number of reports of children born to infected mothers has fallen since 1989. In England and Wales nearly half of maternal infections have been acquired overseas, and the number of children born to these women, and to women who became infected in Britain, is increasing. In south east England the proportion of live births to women whose infection was identified before delivery was only 17% (50/287), compared with 68% (26/38) in Scotland. The vertical transmission rate was 13.7% (23/168), and 23% of infected children developed AIDS in the first year of life. 41% (38/92) of children born to infected mothers who were ascertained after delivery were breast fed, compared with 5% (12/236) of those ascertained before delivery. CONCLUSIONS: The incidence of vertically transmitted HIV infection is increasing in England and Wales. More extensive antenatal testing would enable infected women to be counselled against breast feeding, which could prevent a substantial proportion of vertical transmission in some areas, and would increase opportunities for early diagnosis and treatment of infected children. PMID- 8518569 TI - Assessing long term backache after childbirth. AB - OBJECTIVES: To investigate the factors associated with long term backache after childbirth, to assess all women reporting new onset long term backache, and to investigate any relation with pain relief in labour. DESIGN: Data collected from obstetric records and postal questionnaires or telephone interviews on morbidity after childbirth from all women delivering their first baby between March 1990 and February 1991, followed by analysis of data collected from outpatient consultations. SETTING: St Thomas's Hospital, London. SUBJECTS: Questionnaires were sent to 1615 women who had delivered their first baby in the defined period; 1015 either replied by post or were contacted by telephone. RESULTS: 299 women (29.5% of responders) reported backache lasting more than six months and of these 156 (15.4%) said they had had no back problems previously. Those women who had received epidural analgesia in labour were significantly more likely to report new onset backache (17.8%; 95% confidence interval 14.8% to 20.8%) than those who did not (11.7%; 8.6% to 14.8%). Younger women, unmarried women, and those reporting other antenatal symptoms were significantly more likely to report new long term backache. The 156 women reporting new backache were asked to attend an outpatient clinic and 36 (23%) did so. The majority had a postural backache which was not severe. Psychological factors were present in 14 women. CONCLUSIONS: Though new long term backache is reported more commonly after epidural analgesia in labour, it tends to be postural and not severe. There were no differences in the nature of the backache between those who had or had not received epidural analgesia in labour. PMID- 8518570 TI - Prevalence of primary lactase deficiency in adult residents of west Birmingham. PMID- 8518571 TI - Effectiveness of a nicotine patch in helping people stop smoking: results of a randomised trial in general practice. Imperial Cancer Research Fund General Practice Research Group. AB - OBJECTIVE: To assess the effectiveness of 12 weeks' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet. DESIGN: Double blind placebo controlled randomised trial with a 2 x 2 factorial design. SETTING: 19 general practices in Oxfordshire. SUBJECTS: 1686 heavy smokers aged 25-64 (mean cigarette consumption 24/day; mean duration of smoking 25 years). MAIN OUTCOME MEASURE: Sustained cessation for the last four weeks of the 12 week treatment period, confirmed by saliva cotinine estimation (226/262 cases; 86.3%) or expired carbon monoxide concentration (36/262; 13.7%). Patients lost to follow up (155/1686; 9%) were assumed to have continued to smoke. RESULTS: Cessation was confirmed in 163 patients (19.4%) using the nicotine patch and 99 patients (11.7%) using the placebo patch (difference 7.6% (95% confidence interval 4.2% to 11.1%); p < 0.0001). There was no significant advantage in using the more detailed written support material. The most important adverse effect of the patch was local skin irritation, which occurred in 15.8% (133/842) and 5.1% (43/844) of patients using the nicotine and placebo patches respectively, was graded as severe in 4.8% (40) and 1.1% (nine), and was stated as a reason for withdrawal from the trial in 9.5% (80) and 2.8% (24). CONCLUSION: Nicotine patches are effective in a general practice setting with nursing support, but the extent to which this effect is sustained cannot be assessed until the results of longer term follow up are known. PMID- 8518572 TI - Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. AB - OBJECTIVES: (a) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting; (b) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation. DESIGN: Randomised double blind placebo controlled parallel group study with one year of follow up. SETTING: 30 general practices in 15 English counties. SUBJECTS: 600 dependent heavy smokers (> or = 15 cigarettes daily) who were well motivated to give up. INTERVENTIONS: Brief general practitioner advice, booklet, and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one, three, six, 12, 26, and 52 weeks. MAIN OUTCOME MEASURES: Self reported complete abstinence for up to one year with biochemical validation at all follow up points. RESULTS: Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 (nicotine group 36% of patients (144/400), placebo group 16.5% of patients (33/200)) and of continuous abstinence throughout one year (nicotine group 9.3% (37), placebo group 5.0% (10)). A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3. There were no adverse systemic effects attributable to nicotine, but the incidence of moderate or severe local irritation or itching at the patch site was 16.4% (63 patients), compared with 3.8% (seven) with placebo. CONCLUSION: Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers. PMID- 8518573 TI - How can we best prolong life? Benefits of coronary risk factor reduction in non diabetic and diabetic subjects. AB - OBJECTIVE: To compare the theoretical benefits of different approaches to reduce risk factors for coronary heart disease in subjects at risk. DESIGN: The results of findings from meta-analyses of intervention studies on cause specific mortality and of observational studies on smokers and ex-smokers were applied to observational data on 10 year cause specific mortality derived from the multiple risk factor intervention trial. Lifetable analyses were used to estimate gains in life expectancy. SUBJECTS: Diabetic and non-diabetic men initially 35-57 years of age. MAIN OUTCOME MEASURES: 10 year mortality from coronary heart disease, 10 year total mortality, man years of intervention to prevent one death and one death from coronary heart disease, gain in life expectancy, and drug costs per year of additional life in diabetic and non-diabetic men of 45. RESULTS: In non diabetic men a 10 year mortality from coronary heart disease of 14.4 per 1000 would be reduced by a mean of 0.58, 0.82, 2.64, and 2.74 per 1000 by antihypertensive treatment, lowering cholesterol concentration, taking aspirin, and stopping smoking respectively; a 10 year total mortality of 44.1 per 1000 would fall by a mean of 1.06, 5.16, and 8.65 per 1000 with antihypertensive and aspirin treatment and stopping smoking respectively and increased by a mean of 0.07 per 1000 with the lowering of cholesterol concentration. In diabetic men the reductions in mortality from coronary heart disease would be between three and five times greater, and total mortality would show mean reductions of 5.81, 0.56, 16.17, and 20.84 per 1000 respectively, with all interventions of significant benefit except the lowering of cholesterol concentration. Between 2400 and 3800 man years of pharmacological intervention were calculated as being necessary to prevent one death from coronary heart disease in a non-diabetic man, and between 800 and 1200 man years in a diabetic man. The loss of life expectancy associated with smoking and hypertension is greater than that accruing from hypercholesterolaemia, but stopping smoking would prolong life by a mean of around four years in a 45 year old non-diabetic man and three years in a diabetic man, whereas aspirin and antihypertensive treatment would provide approximately one year of additional life expectancy in both categories. CONCLUSIONS: Studies to date have shown little impact of drugs that lower cholesterol concentration and blood pressure on either coronary heart disease or total mortality. Although new treatments for hypercholesterolaemia and hypertension might help prevent coronary heart disease, other approaches to reduce the burden of premature death are required. PMID- 8518574 TI - Measurement error in the Hawksley random zero sphygmomanometer: what damage has been done and what can we learn? AB - The Hawksley random zero sphygmomanometer is used in all aspects of blood pressure research, from clinical trials to evaluation of new blood pressure recorders. It is designed to reduce observer bias in blood pressure measurement. The problem is that it also underestimates blood pressure. Furthermore, this was first reported more than two decades ago. In this paper Ronan Conroy and colleagues explore the consequences of using an inaccurate instrument for important research and why prestigious organisations like the World Health Organisation continue to use it. PMID- 8518575 TI - Teaching communication skills to clinical students. AB - Seven years' experience in teaching communication skills to first year clinical students at St Mary's Hospital School of Medicine is described. The first component consists of a day during the introductory clinical course; this is divided into a lecture and small seminar groups and involves behavioural scientists and clinicians from many departments. The second component uses simulated patients and video feedback and takes place in small groups later in the year. Participation of the students through active critical discussion, role play, and interactive video feedback are important aspects in the success of the course. The methods have been refined through evaluation by students and tutors. This article aims to allow others, already running or considering such a course, to develop effective courses within the practical constraints of their own institutions. PMID- 8518576 TI - A BMA secretary for quality. Interview by Richard Smith. PMID- 8518577 TI - ABC of sleep disorders. Psychotropic drugs and sleep. PMID- 8518578 TI - AIDS epidemic in Africa. Channel four tackles controversy. PMID- 8518579 TI - Hypertension guidelines. Other diseases complicate management. PMID- 8518580 TI - Long term care of elderly people. Hospital should remain an option. PMID- 8518581 TI - Long term care of elderly people. Residential homes challenges GPs. PMID- 8518582 TI - Long term care of elderly people. Dependency increasing in Manchester. PMID- 8518583 TI - Dural puncture. Blood patch not always benign. PMID- 8518584 TI - Dural puncture. Rotating needle increases risk. PMID- 8518585 TI - Foreign body aspiration. PMID- 8518586 TI - Alcohol not a predictor of peripheral oedema in chronic bronchitis. PMID- 8518587 TI - Non-medical use of ketamine. PMID- 8518588 TI - One fee for night visits. PMID- 8518589 TI - Chest infections in African children. Clinical signs unreliable. PMID- 8518590 TI - Chest infections in African children. Respiratory rate poor predictor of hypoxaemia. PMID- 8518591 TI - Presenile dementia. Dementia classification misleading. PMID- 8518592 TI - Presenile dementia. Gender difference unlikely. PMID- 8518593 TI - Presenile dementia. Risk to women inflated by artefact. PMID- 8518594 TI - Urinary incontinence. GPs lack confidence. PMID- 8518595 TI - Hypercalcaemia with topical calcipotriol. PMID- 8518596 TI - Multiple author trend worst in medicine. PMID- 8518598 TI - The GMC: size and public accountability. PMID- 8518597 TI - The problem with cholesterol. PMID- 8518599 TI - Bone gain and loss in premenopausal women. PMID- 8518600 TI - Rural health and health care. PMID- 8518601 TI - Home treatment for acute psychiatric disorder. PMID- 8518603 TI - Prognostic index for recurrence of seizures after remission of epilepsy. Medical Research Council Antiepileptic Drug Withdrawal Study Group. AB - OBJECTIVES: To develop and test a prognostic index for the recurrence of seizures after a minimum remission of seizures of two years in people with a history of epilepsy. DESIGN: Information from a large prospective randomised study of withdrawal of antiepileptic drugs was used to identify clinical and treatment factors of prognostic importance in determining the recurrence of seizures. A split sample approach was used to test the internal validity of predictions made on the basis of identified prognostic factors. SETTING: Centres in six European countries. MAIN OUTCOME MEASURES: Comparison of predicted and observed rates of recurrence of seizure. SUBJECTS: 1013 patients randomised to the Medical Research Council study for antiepileptic drug withdrawal. RESULTS: The Cox proportional hazards model identified several factors that increased the risk of seizures recurring. These included being 16 years or older; taking more than one antiepileptic drug; experiencing seizures after starting antiepileptic drug treatment; a history of primary or secondarily generalised tonic-clonic seizures; a history of myoclonic seizures; and having an abnormal electroencephalogram. The risks of seizures recurring decreased with increasing time without seizures. The model allowed estimation of the risk of seizures recurring in the next one and two years under the policies of continued antiepileptic drug treatment and slow withdrawal of drugs. Split sample validation suggested that the model was well calibrated. CONCLUSION: The model is currently the best available aid for counselling the many patients in the community with epilepsy currently in remission who seek advice about the risks of seizures recurring if they stop antiepileptic drug treatment. The model requires validation in a broad population of patients, and such studies are in progress. PMID- 8518604 TI - Risk of fatal accidents occurring other than at sea among Icelandic seamen. AB - OBJECTIVE: To study mortality among seamen, particularly from fatal accidents that occurred other than at sea. DESIGN: Cohort study. SETTING: Iceland. SUBJECTS: 27,884 seamen, both fishermen and sailors from the merchant fleet, who had been members of a pension fund from 1958 to 1986. MAIN OUTCOME MEASURES: Cause of death (ICD seventh revision), standardised mortality ratio. RESULTS: Most standardised mortality ratios were greater than 1, being 1.26 for all causes and 1.83 for all external causes. There was no healthy worker effect. The excess of deaths from all external causes included all subcategories of death from accidents, poisonings, and violence and not just accidents at sea (water transport accidents, ICD codes E850-E858). A significant trend was found for length of employment and mortality from all accidents at sea, drowning at sea, accidental poisoning, other accidents, and accidental drowning; correlation coefficients for all causes, all accidents, suicide, and injuries undetermined whether accidentally or purposely inflicted were 0.7-0.8. Compared with seamen who started work during 1968-77, those who started work in 1978 or later had higher mortality from all causes, road traffic accidents, poisoning, other accidents, homicide, and injuries unknown whether accidentally or purposely inflicted, but not from all accidents at sea and accidental drowning. CONCLUSION: Seamen seem to be a special group with a high risk of fatal accidents occurring not only at sea. The association between fatal accidents other than at sea and length of employment as seamen indicates that seamen are modified by their occupation towards hazardous behaviour or a risky lifestyle. PMID- 8518605 TI - Diagnosis of sex in preimplantation embryos by fluorescent in situ hybridisation. PMID- 8518602 TI - Cholesterol lowering and mortality: the importance of considering initial level of risk. AB - OBJECTIVE: To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN: Meta analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS: Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES: Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS: In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION: Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs should be advocated. Future trials should aim to clarify the level of risk above which treatment is of net benefit. PMID- 8518606 TI - Relation between night visit rates and deprivation measures in one general practice. AB - OBJECTIVE: To compare night visit rates in different electoral wards of one general practice with the Jarman and Townsend deprivation scores and unemployment rates. DESIGN: Analysis of computerised workload data. SETTING: General practice in centre of Mansfield, Nottinghamshire. OUTCOME MEASURE: Visits made in 588 nights to the 11,998 patients on the practice list. RESULTS: Night visit rates in 15 electoral wards varied from 19.6 to 55.3 visits per 1000 patients per year. The rates showed a significant association with the Townsend score (p = 0.004) and the unemployment rate (p = 0.03) but not with the Jarman score (p = 0.3). The Townsend score explained 49% of the variability; unemployment explained 31% and the Jarman score explained 9%. CONCLUSIONS: Even in a general practice not eligible for deprivation payments there was a 2.8-fold variation in night visit rates between wards. In this practice the Townsend score was significantly better at predicting night visit rates than the Jarman score. This method of looking at internal variation in workloads in computerised practices could give more direct data on the relation between deprivation and general practice workload than has previously been available. PMID- 8518607 TI - Epidemiological study of wheeze, doctor diagnosed asthma, and cough in preschool children in Leicestershire. AB - OBJECTIVE: To determine the cumulative prevalences of wheeze and doctor diagnosed asthma and the point prevalences of recurrent cough and wheeze in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on regional authority's child health index for immunisation; questionnaire completed by parents. SETTING: Leicestershire. SUBJECTS: 1650 white children born in 1985-9 who were surveyed in 1990. MAIN OUTCOME MEASURES: Cumulative prevalences of wheeze and doctor diagnosed asthma and point prevalences of recurrent cough and wheeze by age and sex. RESULTS: There were 1422 replies (86.2%; 726 for boys, 696 for girls). Overall, 11.0% (95% confidence interval 9.4% to 12.6%) of children had formally been diagnosed as having asthma, the cumulative prevalence in boys (12.7%) being somewhat higher than in girls (9.2%) (age adjusted odds ratio 1.47, p = 0.03). As expected, the cumulative prevalence of asthma increased significantly with age (7.5% (13/173) in children under 1 year, 15.9% (61/383) in children of 4 years and over; p < 0.001). The cumulative prevalence of wheeze overall was 15.6% (13.7% to 17.5%), being higher in boys (17.6%) than in girls (13.5%) (odds ratio 1.38, p = 0.03). The overall prevalence of recurrent cough without colds was 21.8% (19.6% to 23.9%), with a non-significant excess in boys (23.1% v 20.4%). The overall prevalence of wheezing attacks during the previous 12 months was 13.0% (11.3% to 14.8%) with a non-significant excess in boys (14.5% v 11.5%). CONCLUSIONS: These findings are baseline results and emphasise the importance of studying the age group of interest rather than relying on the recall of parents of school age children. PMID- 8518608 TI - Research samples from families with genetic diseases: a proposed code of conduct. AB - Research on samples from families with genetic disease underlies many of the major advances that are occurring in medical genetics. But ethical and practical problems may arise when samples from relatives who are healthy but at risk are included in such studies. In particular, new molecular tests for specific gene mutations may result in the detection of a genetic defect in relatives who had neither expected this possibility nor given specific consent to such testing. Family members at risk should not be included in such studies unless strictly necessary, and in such cases specific consent should be obtained and information should be given about the implications of an abnormal result of a test. This is particularly important when stored samples from previous studies without such implications are being reused and is also relevant to the genetic testing of samples taken primarily for epidemiological studies of disorders when only a small proportion of cases is thought to be genetic in origin. There is a need for guidelines to protect both subjects and investigators in a field which is spreading rapidly and involving many clinical and laboratory research workers previously unfamiliar with genetic testing. PMID- 8518609 TI - Building a city wide service for exchanging needles and syringes. AB - How best can injecting drug misusers obtain clean injecting equipment in a city where drug injecting is widespread? An exchange service for needles and syringes throughout Glasgow has been established in health centres and clinics in the evening. Over the past four years seven new exchanges have been opened and over 2700 injecting drug misusers have attended. Attendances rose from under 1000 in 1988 to 28,000 in 1992. The exchanges also provide a wide range of other health and social services. Public hostility to the exchanges has abated. During the same period equipment sharing in the city diminished and the observed prevalence of HIV among injecting drug misusers stabilised at around 1%. PMID- 8518610 TI - Continuing medical education: experience and opinions of consultants. AB - The right of consultants to study leave and expenses is not binding on trusts and has been eroded in directly managed units. Complaints led to a survey of consultants in North West Thames region. This showed that most consultants use their own time and money to maintain their knowledge by buying and consulting journals and textbooks, attending local meetings, and using their annual leave for study, but they feel the need for study leave to attend meetings of specialist societies and courses. Leave is usually granted readily but without cover provided by a locum and with a very limited contribution to expenses. To maintain quality of medical care both the right and obligation to take study leave should be contractual. PMID- 8518611 TI - ABC of sleep disorders. Medical problems during sleep. PMID- 8518612 TI - Access to heart surgery for smokers. Denying access more costly. PMID- 8518613 TI - Access to heart surgery for smokers. Each patient a special case. PMID- 8518614 TI - Access to heart surgery for smokers. Smokers waste valuable resources. PMID- 8518615 TI - Access to surgery for smokers. Denying treatment is indefensible. PMID- 8518616 TI - Access to heart surgery for smokers. Higher complication rate not confined to smokers. PMID- 8518617 TI - Access to heart surgery for smokers. Inform, don't punish. PMID- 8518618 TI - Upper age limit for cervical screening. PMID- 8518619 TI - Students like new curriculum. PMID- 8518620 TI - Uses of heparin. Ancrod for heparin induced thrombocytopenia. PMID- 8518621 TI - Uses of heparin. Withhold in acute ischaemic stroke. PMID- 8518622 TI - Psychiatry services for elderly people. Team approach to assessment unproved. PMID- 8518623 TI - Health inequalities in Australia. PMID- 8518624 TI - Leukemia in children whose parents have been exposed to radiation. PMID- 8518625 TI - Cerebral herniation in bacterial meningitis. PMID- 8518626 TI - Induction of labour at term. Women not for waiting. PMID- 8518627 TI - Induction of labour at term. Evidence on outcome favours induction. PMID- 8518628 TI - Injecting drug users in Edinburgh. Fewer drug users share needles. PMID- 8518629 TI - Resource allocation. PMID- 8518630 TI - Using Medline for comprehensive searches. PMID- 8518631 TI - Medical messages on television. Grapevine effect. PMID- 8518632 TI - Health and human rights in Gaza. PMID- 8518633 TI - Attachments in general practice for hospital trainees. PMID- 8518634 TI - General practitioners' performance. PMID- 8518635 TI - Jaundice persisting beyond 14 days after birth. PMID- 8518636 TI - Clozapine: progress in treating refractory schizophrenia. PMID- 8518637 TI - What does London need from its ambulance service? PMID- 8518638 TI - Measuring patients' views: the optimum outcome measure. PMID- 8518639 TI - Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. AB - OBJECTIVES: To gain population norms for the short form 36 health survey questionnaire (SF36) in a large community sample and to explore the questionnaire's internal consistency and validity. DESIGN: Postal survey by using a booklet containing the SF36 and several other items concerned with lifestyles and illness. SETTING: The sample was drawn from computerised registers of the family health services authorities for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. SAMPLE: 13,042 randomly selected subjects aged 18-64 years. MAIN OUTCOME MEASURES: Scores for the eight health dimensions of the SF36. RESULTS: The survey achieved a response rate of 72% (n = 9332). Internal consistency of the different dimensions of the questionnaire was high. Normative data broken down by age, sex, and social class were consistent with those from previous studies. CONCLUSIONS: The SF36 is a potentially valuable tool in medical research. The normative data provided here may further facilitate its validation and use. PMID- 8518640 TI - The SF36 health survey questionnaire: an outcome measure suitable for routine use within the NHS? AB - OBJECTIVE: To assess the validity, reliability, and acceptability of the short form 36 (SF 36) health survey questionnaire (a shortened version of a battery of 149 health status questions) as a measure of patient outcome in a broad sample of patients suffering from four common clinical conditions. DESIGN: Postal questionnaire, followed up by two reminders at two week intervals. SETTING: Clinics and four training practices in north east Scotland. SUBJECTS: Over 1700 patients aged 16-86 with one of four conditions--low back pain, menorrhagia, suspected peptic ulcer, or varicose veins--and a comparison sample of 900 members of the general population. MAIN OUTCOME MEASURES: The eight scales within the SF36 health profile. RESULTS: The response rate exceeded 75% in the patient population (1310 respondents). The SF36 satisfied rigorous psychometric criteria for validity and internal consistency. Clinical validity was shown by the distinctive profiles generated for each condition, each of which differed from that in the general population in a predictable manner. Furthermore, SF36 scores were lower in referred patients than in patients not referred and were closely related to general practitioners' perceptions of severity. CONCLUSIONS: These results provide support for the SF36 as a potential measure of patient outcome within the NHS. The SF36 seems acceptable to patients, internally consistent, and a valid measure of the health status of a wide range of patients. Before it can be used in the new health service, however, its sensitivity to changes in health status over time must also be tested. PMID- 8518641 TI - Protection of children by their mothers against sunburn. PMID- 8518642 TI - Community mothers' programme: randomised controlled trial of non-professional intervention in parenting. AB - OBJECTIVE: To see whether non-professional volunteer community mothers could deliver a child development programme to disadvantaged first time mothers for children aged up to 1 year. DESIGN: Randomised controlled trial. SETTING: A regional health authority in Dublin. SUBJECTS: 262 first time mothers who were delivered during six months in 1989 and who lived in a deprived area of Dublin; 30 experienced mothers from the same community recruited as community mothers. INTERVENTIONS: All the first time mothers received standard support from the public health nurse. In addition, those in the intervention group received the services of a community mother, who was scheduled to visit monthly during the first year of the child's life. RESULTS: 232 (89%) first time mothers completed the study--127 in the intervention group, 105 controls. At the end of the study children in the intervention group were more likely to have received all of their primary immunisations, to be read to, and to be read to daily, played more cognitive games; and were exposed to more nursery rhymes. They were less likely to begin cows' milk before 26 weeks and to receive an inappropriate energy intake and inappropriate amounts of animal protein, non-animal protein, wholefoods, vegetables, fruit, and milk. Mothers in the intervention group also had a better diet than controls. At the end of the study they were less likely to be tired, feel miserable, and want to stay indoors; had more positive feelings; and were less likely to display negative feelings. CONCLUSION: Non-professionals can deliver a health promotion programme on child development effectively. Whether they can do so as effectively as professionals requires further study. PMID- 8518643 TI - What are the complications of influenza and can they be prevented? Experience from the 1989 epidemic of H3N2 influenza A in general practice. AB - OBJECTIVES: In an epidemic: to measure the incidence and risk of complications of influenza; to determine the effect of pre-existing disease on complications; to estimate vaccine uptake and efficacy. DESIGN: Case-control study. SETTING: Primary care: two group practices. SUBJECTS: 342 of the 395 cases of clinically diagnosed influenza reported to the general practice surveillance of infectious diseases scheme of the Public Health Laboratory Service during the 1989 epidemic, and 342 age and sex matched controls. INTERVENTIONS: Examination of records. MAIN OUTCOME MEASURES: Documented recognised complications; hospital admission; previous vaccination. RESULTS: Of 15 recognised complications, bronchitis was the commonest (rate 190.1/1000 cases) and significantly commoner in cases (summary odds ratio 9.7) after adjusting for higher consultation rates (mean 6.1 per annum v 4.2 among controls; p < 0.0001). No deaths were recorded. The risk of bronchitis complicating influenza was higher in patients with pre-existing illnesses regarded as an indication for vaccination (odds ratio 3.3; p < 0.0001). Observed vaccination efficacy in those with pre-existing illnesses and in elderly subjects was high (63% and 77% respectively) but uptake was low (4.5% and 6.1% respectively). CONCLUSIONS: Bronchitis complicates about one fifth of all cases of influenza presenting to general practitioners. Patients with pre-existing illnesses regarded as an indication for vaccination are particularly at risk. Vaccine uptake is extremely low, precluding an unequivocal demonstration of a protective effect. PMID- 8518644 TI - The first ascent of Mount Everest. PMID- 8518645 TI - Can children withhold consent to treatment? AB - A dilemma exists when a doctor is faced with a child or young person who refuses medically indicated treatment. The Gillick case has been interpreted by many to mean that a child of sufficient age and intelligence could validly consent or refuse consent to treatment. Recent decisions of the Court of Appeal on a child's refusal of medical treatment have clouded the issue and undermined the spirit of the Gillick decision and the Children Act 1989. It is now the case that a child patient whose competence is in doubt will be found rational if he or she accepts the proposal to treat but may be found incompetent if he or she disagrees. Practitioners are alerted to the anomalies now exhibited by the law on the issue of children's consent and refusal. The impact of the decisions from the perspectives of medicine, ethics, and the law are examined. Practitioners should review each case of child care carefully and in cases of doubt seek legal advice. PMID- 8518647 TI - The Freeman hospital: disillusionment sets in. PMID- 8518646 TI - Tempting fate: control of communicable disease in England. AB - Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types. PMID- 8518648 TI - ABC of sleep disorders. Sleep and sleep problems in elderly people. PMID- 8518649 TI - Health care in London. BMA slow to condemn Tomlinson. PMID- 8518650 TI - Health care in London. Inadequate provision for long-term care. PMID- 8518651 TI - Health care in London. Other cities also overbedded. PMID- 8518652 TI - Health care in London. London low on residential and nursing homes. PMID- 8518653 TI - Triazolam. As safe as other benzodiazepines. PMID- 8518654 TI - Sleep disorders. Epilepsy a differential diagnosis in children. PMID- 8518655 TI - Triazolam. ...and selective referencing. PMID- 8518656 TI - Triazolam. Triazolam condemned by misinformation... PMID- 8518657 TI - Sleep disorders. Consider nocturnal paroxysmal dystonia. PMID- 8518658 TI - Sleep disorders. Nasendoscopy before surgery for snoring. PMID- 8518659 TI - Sleep disorders. Simple treatment for night terrors. PMID- 8518660 TI - Sleep disorders. Steroids cause sleep disturbance. PMID- 8518661 TI - Chickenpox in pregnancy. Incidence underestimated. PMID- 8518662 TI - Chickenpox in pregnancy. Pneumonitis more severe. PMID- 8518663 TI - Surveillance of congenital anomalies. False economies. PMID- 8518664 TI - Antenatal HIV testing. Anonymous testing misleads patients. PMID- 8518665 TI - Surveillance of congenital. Anophthalmia under scrutiny. PMID- 8518666 TI - Antenatal HIV testing. Dedicated counsellors needed. PMID- 8518667 TI - Superficial bladder cancer. PMID- 8518668 TI - Selective decontamination of the gut. PMID- 8518669 TI - Europe's poor response to refugees from former Yugoslavia. PMID- 8518670 TI - Immediate coronary angioplasty for acute myocardial infarction. PMID- 8518671 TI - Tinnitus: its causes, diagnosis, and treatment. PMID- 8518672 TI - Sickle cell disease: the case for coordinated information. PMID- 8518673 TI - At last a strategy for British science. PMID- 8518674 TI - Providing citizens' advice in general practice. PMID- 8518675 TI - Insurers inconsistent over HIV. PMID- 8518676 TI - Asbestos and lung cancer in Glasgow and the west of Scotland. AB - OBJECTIVE: To quantify the relation between lung cancer and exposure to asbestos in men in west Scotland and to estimate the proportion of lung cancer which may be attributed to exposure to asbestos. DESIGN: An ecological correlation study of the incidence of lung cancer in men and past asbestos exposure. The unit of analysis was the postcode sector. Correction was made for past cigarette smoking, air pollution, and deprivation. SETTING: The region covered by the west of Scotland cancer registry, containing 2.72 million people and including Glasgow and the lower reaches of the River Clyde, where shipbuilding was once a major industry. SUBJECTS: All men diagnosed with lung cancer between 1975 and 1984 whose residence at the time of registration was within the west of Scotland. MAIN OUTCOME MEASURE: The population attributable risk for asbestos related lung cancer. RESULTS: An estimated 5.7% (95% confidence interval 2.3 to 9.1%) of all lung cancers in men registered in the west of Scotland during the period 1975-84 were asbestos related, amounting to 1081 cases. CONCLUSIONS: A considerable proportion of cases of lung cancer in men in Glasgow and the west of Scotland from 1975 to 1984 were asbestos related. Most of these may not have been considered for compensation by the Department of Social Security. Given the very small annual number of recorded cases of asbestosis this condition is probably not a prerequisite for the development of asbestos related lung cancer. A heightened awareness of the increasing incidence of asbestos related neoplasms and their more thorough investigation are recommended. PMID- 8518677 TI - A prospective study of alcohol consumption and bone mineral density. AB - OBJECTIVES: To study the effects of alcohol consumption on bone mineral density in a defined population. DESIGN: Prospective study of bone mineral density, measured during 1988-91, in a cohort who had given baseline data on alcohol intake in the previous week and in the previous 24 hours and other factors affecting bone mineral density during 1973-5. SETTING: Rancho Bernardo, California. SUBJECTS: 182 men and 267 women aged 45 and over at baseline, half having been randomly selected and half having been chosen for hyperlipidaemia, who gave baseline information on alcohol intake in one week. Of these subjects, 142 men and 220 women gave information on alcohol intake in 24 hours. MAIN OUTCOME MEASURES: Bone mineral density of the radial shaft, ultradistal wrist, femoral neck, and lumbar spine. RESULTS: Men and women were considered separately, and the tertiles of alcohol consumption were used to delineate low, medium, and high values of alcohol intake. With increasing alcohol intake in one week, bone mineral density (adjusted for age, body mass index, smoking, taking exercise, and oestrogen replacement therapy in women) increased significantly in the femoral neck of men (p < 0.01) and the spine of women (p < 0.01). With increasing alcohol intake in 24 hours, adjusted bone mineral density increased significantly in the radial shaft (p < 0.05) and spine (p < 0.001) of women. Similar, but not significant, patterns were seen at the other bone sites. CONCLUSIONS: Social drinking is associated with higher bone mineral density in men and women. PMID- 8518678 TI - Risk assessment adjusted for gestational age in maternal serum screening for Down's syndrome. AB - OBJECTIVE: To investigate the relation between errors in calculation of gestational age and assessment of risk of Down's syndrome and to analyse the implications for screening programmes. DESIGN: Retrospective analysis of dating of gestational age by menstrual history v ultrasound scan. Computer program with maternal age and concentrations of alpha fetoprotein and free beta human chorionic gonadotrophin to calculate risk for a range of expected dates of delivery. Computer simulated prospective application of new screening programme. SETTING: Teaching hospitals in Nottingham. SUBJECTS: 31,561 women with singleton pregnancies with gestational age based on routine ultrasound scan. Computer simulation of 20,000 women in three age ranges (up to 37; up to 40; all). MAIN OUTCOME MEASURES: Distribution of error between gestational age based on ultrasound scan v menstrual history. Proportion of women in the population who require precise dating of pregnancy; proportion of women who require amniocentesis. RESULTS: With gestational age derived from ultrasound scan as reference the 95% confidence interval for gestational age by menstrual history was -27 to +9 days. A screening programme for Down's syndrome for women up to age 40 would yield a low risk (< 1:250) for this range of days in 86.0% of cases. The 14.0% of women remaining would have one or more high risk values in their report and would thus require an ultrasound scan for precise dating of the pregnancy; 30% of these--that is, 3.7% of the screened population--would be identified as high risk and require consideration for amniocentesis. CONCLUSIONS: Screening programmes for Down's syndrome require the facility for precise dating of pregnancy to improve the accuracy of risk assessment. This can be achieved without introducing additional scans for early dating in the whole population but by selecting only those cases (about 14%) when an error in dates is likely to affect the risk of Down's syndrome. PMID- 8518679 TI - Use of dipsticks for routine analysis of urine from children with acute abdominal pain. PMID- 8518680 TI - Invasive procedures in children receiving intensive care. PMID- 8518681 TI - Association between availability of non-prescription beta 2 agonist inhalers and undertreatment of asthma. AB - OBJECTIVE: To determine whether the availability of beta 2 agonist inhalers without prescription leads to undertreatment of asthma. DESIGN: Cross sectional study of adequacy of treatment in asthmatic subjects who purchased beta 2 agonist inhalers and subjects who obtained inhalers by prescription. SETTING: Community pharmacies in New South Wales, Australia. SUBJECTS: 403 eligible consecutive asthmatic subjects aged 13 to 55 purchasing salbutamol metered dose inhalers over the counter or by prescription; 197 attended for follow up and spirometry and 139 returned 14 day symptom, peak flow, and medication diaries. MAIN OUTCOME MEASURES: Severity of asthma assessed on frequency of day time and night time wheezing, frequency of inhaler use, and peak expiratory flow rates. Adequacy of treatment according to published guidelines. RESULTS: Of the 139 patients who completed the diary 83, (60%) purchased their inhalers without prescription and 83 were undertreated. The characteristics of patients in the prescription and purchasing groups were similar. Multiple logistic regression analysis identified use of non-prescribed salbutamol as being associated with a 2.9-fold increase in the odds of undertreatment (95% confidence interval 1.3 to 6.8). Smoking increased the odds of undertreatment (3.3, 1.2 to 9.5) and use of a peak flow meter reduced the odds (0.11, 0.04 to 0.34). Adjustment for frequency of consultation made use of non-prescription salbutamol insignificant (1.4, 0.55 to 3.8). Attitudes to services provided by doctors and pharmacists were favourable and not associated with undertreatment. CONCLUSION: Over the counter purchase of salbutamol is associated with infrequent consultation with doctors and undertreatment of asthma. PMID- 8518682 TI - Citizens' advice in general practice. AB - OBJECTIVE: To examine the introduction of citizens advice bureau sessions into general practice. DESIGN: Prospective survey of 150 consecutive attenders. SETTING: 10 Practices in south Birmingham that volunteered to participate. OUTCOME MEASURES: The social characteristics of the population attending, the problems presented, the social security and other payments obtained, and the health problems mentioned during the sessions. RESULTS: Advice requested covered the whole range offered by the citizens advice bureaus. Thirty nine of 150 attenders obtained payments totalling 58,300.58 pounds for year 1991-2, of which 54,929.58 pounds was recurring. People mentioning health problems were significantly more likely to be entitled to unclaimed benefits. CONCLUSIONS: The provision of citizens advice bureau sessions in general practice is an effective way of providing advice on life problems and securing proper payment of benefits, particularly to patients with health problems. This service complements rather than detracts from other citizens advice bureau activities. PMID- 8518683 TI - The new NHS: the second year. West Suffolk: a new landscape. PMID- 8518685 TI - Systemic thrombolysis causing haemorrhage around a prosthetic abdominal aortic graft. PMID- 8518684 TI - Thallium poisoning. Diagnosis may be elusive but alopecia is the clue. AB - Thallium is a heavy metal whose salts are used in some rodent poisons and in the manufacture of optical lenses, semiconductors, scintillation counters, low temperature thermometers, and switching devices, green coloured fireworks, and imitation jewelery, and as chemical catalysts. In clinical practice thallium isotopes are used in cardiac scanning, but the use of thallium salts to treat scalp ringworm was abandoned earlier this century because of their toxicity. The sale of thallium in Britain is strictly licensed because of its toxicity and potential for use in murder, which is helped by the fact that thallous salts are colourless, tasteless, and odorless. The more water soluble salts (such as thallium sulphate, acetate, or carbonate) have higher toxicity, and although the toxic dose is variable most deaths occur after the ingestion of 10-15 mg/kg of soluble salt. Most cases of thallium toxicity occur after oral ingestion but severe toxicity has been reported after inhalation of contaminated dust from pyrite burners, in zinc and lead smelting, and in the manufacture of cadmium, after dermal absorption through protective rubber gloves, and after snorting what was thought to be cocaine. The elimination half time of thallium is between 1.7 and 30 days depending on the time since, and chronicity of, ingestion. The elimination time phases are apparent and because of the long terminal elimination half time thallium may act as a cumulative poison. We present two cases of thallium poisoning with intent to kill. PMID- 8518686 TI - ABC of sleep disorders. Sleep problems in patients with medical illness. PMID- 8518687 TI - Who should manage vascular disease? Geriatricians...? PMID- 8518688 TI - Who should manage vascular disease? Radiologists...? PMID- 8518689 TI - Who should manage vascular disease? Surgeons...? PMID- 8518690 TI - Who should manage vascular disease? Or any specialist with an interest? PMID- 8518691 TI - Management of trauma. Deserves high priority. PMID- 8518692 TI - Management of trauma. Nitrous oxide dangerous in pneumothorax. PMID- 8518693 TI - Reporting deaths to the coroner. Doctors abuse the coronial system. PMID- 8518694 TI - Medical management of miscarriage. Psychological impact underestimated. PMID- 8518695 TI - Reporting deaths to the coroner. Pressure sores underreported. PMID- 8518696 TI - Medical management of miscarriage. Should we intervene in uncomplicated miscarriage? PMID- 8518697 TI - Coding of clinical diagnoses. Clerical and medical errors contribute to inaccuracy. PMID- 8518698 TI - Coding of clinical diagnoses. Persevere with Korner system. PMID- 8518699 TI - Hepatitis C from immunoglobin infusions. PMID- 8518700 TI - Intraocular foreign body missed by computed tomography. PMID- 8518701 TI - Cimetidine and weight loss. PMID- 8518702 TI - Dipstick testing easy and informative. PMID- 8518703 TI - No charge for unique service. PMID- 8518704 TI - Patients as friends. PMID- 8518705 TI - Zidovudine unproved in AIDS dementia. PMID- 8518706 TI - Children are losing their teeth. PMID- 8518707 TI - Deprivation payments fairer in Scotland. PMID- 8518708 TI - Use caution in prescribing desmopressin for nocturnal enuresis. PMID- 8518709 TI - The preventive paradox: a critical examination. PMID- 8518710 TI - The tail of the alcohol consumption distribution. AB - The consumption containment rate (CCR), proposed by Taylor as a way of characterizing the upper tail of the alcohol consumption distribution, is analyzed and estimated from a collection of data sets from different countries. It is found that CCR curves for different countries are highly different at low consumption levels. However, at high consumption levels, they are remarkably similar across cultures. It is proposed that this may be due to cross-cultural similarities in heavy drinking careers. PMID- 8518711 TI - Developments in drinking behavior in The Netherlands from 1958 to 1989, a cohort analysis. AB - Alcohol consumption in the Netherlands increased at a very fast rate from 1960 to 1975, especially among young men. The question is raised whether members of the cohort that started drinking during the 1960s show a lasting deviation from cohorts born earlier with respect to drinking behavior. Cohort analysis is used to assess the effects of aging, period and cohort membership on changes in abstinence, mean consumption and heavy drinking in the Netherlands in the last three decades. Social interaction theory (Skog, 1980) is used as an interpretative framework. Conclusions are that abstinence is related to aging, while mean consumption and heavy drinking are associated with period effects. Populations of men and women appear to change drinking behavior collectively. Results on women are more regular than those on men. PMID- 8518712 TI - Paternal lineage of alcoholism, cohort effects, and alcoholism criteria. AB - Adoption studies have led to the suggestion that there may be two distinct subgroups of alcoholics with differing genetic contributions. Among 249 male alcoholics we used discriminant analysis to relate the features of type 1 and type 2 alcoholism to the presence or absence of a family history of alcoholism in male paternal relatives. We found that guilt and binging, features usually attributed to type 1 (milieu-limited) alcoholism, were in fact more prevalent in the family history positive group. An additional cohort analysis found cohort related variations in type 1/type 2 characteristics. The possible implications of these findings are discussed. PMID- 8518713 TI - The association between severity of DSM-III-R alcohol dependence and medical and social consequences. AB - This paper describes the relationship between severity of dependence and medical and social consequences in a clinical sample. Respondents constitute a sample of 219 men and 162 women interviewed in nine alcohol programs in a Northern California county. Results suggest that the number of dependence indicators reported by respondents is a valid indicator of severity of alcohol dependence, and that there is a positive relationship between the number of indicators and the number of medical and social consequences reported by respondents. When specific medical and social consequences are examined, an analysis restricted to men only, the number of dependence indicators is associated with stomach, heart and liver problems, DTs, hallucinations, public drunkenness, family arguments and serious accidents, but it is not associated with drunk driving arrests and job problems. PMID- 8518714 TI - Mortality in a sample of convicted drinking drivers. AB - Mortality rates for 639 drinking drivers were calculated. The sample consisted of all individuals convicted of a second offence in two Ontario cities (Oshawa and North Bay) between 1973 and late 1978. There were 53 deaths (51 males, 2 females) in the sample prior to the end of 1986. Among males, significant excess total mortality was observed (Standardized Mortality Ratio = 1.7); similar trends were observed among females. Age-related excess mortality and excess mortality by cause were strikingly similar to mortality patterns observed among alcoholics. PMID- 8518715 TI - The reversibility of alcoholic brain damage is not due to rehydration: a CT study. AB - Alcoholic brain damage is reversible when the patients are continually abstinent. An increase of brain water content was the putative explanation for this phenomenon. We tested the rehydration hypothesis using CT density measurements in 29 alcohol-dependent male inpatients. During a 5-week period of controlled abstinence, CT density measures did not decrease in any of the investigated regions of the brain as one would expect with an increase in brain water. Although the volumetry of the ventricular system and the subarachnoidal spaces revealed a significant reduction of CSF volume, we found a slight increase in CT density measures. Thus, our results are in contradiction to the rehydration hypothesis. Under discussion is whether neuronal plasticity might be the explanation of the reversibility of alcoholic brain damage in abstinent patients. PMID- 8518716 TI - Doctors and substance misuse: types of doctors, types of problems. AB - The casenotes of 144 doctors who had received treatment for substance misuse were analysed. There were no differences between general practitioners (n = 61) and hospital doctors (n = 58) in terms of their substance misuse histories or the problems they incurred. Differences emerged between the consultant (n = 24) and the non-consultant (n = 34) grades of hospital doctor. The consultants were older at onset of problematic use (42.6 +/- 8.6 vs. 29.9 +/- 9.8 years); they suffered fewer career problems and misused fewer substances. The most frequent pathways into substance use were personality difficulties (76 subjects, 52.8%) and anxiety or depression (46 subjects, 31.9%). A history of depression (n = 36) was associated with perceived stress at work (p = 0.014), and at home (p = 0.06). Past neurotic disturbances (n = 20) were associated with personality difficulties (p = 0.035), anxiety or depression (p = 0.004), and with an earlier onset of problematic substance use (30.2 +/- 8.3 vs. 36.5 +/- 9.8 years, p = 0.014). Principal components of possible antecedents yielded one major component on which all elements loaded; this was labelled the 'disturbance score'. This score showed a reduction with increasing age of onset of problematic substance use. PMID- 8518717 TI - Religiosity and attitudes towards drug use among 13-15 year olds in England. AB - A sample of 4753 13-15 year olds attending the third and fourth year classes of 29 secondary schools completed a questionnaire concerned with attitudes towards the use of alcohol, butane gas, glue, heroin, marijuana and tobacco, together with indices of religious affiliation, belief and practice. The data demonstrated that young adolescents' attitudes towards drug use varies considerably from one substance to another and that religiosity is a significant predictor of attitudes towards the use of each of the substances included in the survey. PMID- 8518718 TI - The validity of injecting drug users' self-reports about sexually transmitted diseases: a comparison of survey and serological data. AB - Researchers studying the validity of injecting drug users' self-reports have often reported a high degree of correspondence between self-reports and several types of criterion variables. In this study, injecting drug users' responses to questions about prior infection with four sexually transmitted diseases were compared with serological test data. For three of the four diseases studied, discrepancies between survey and serological results were quite large, especially when respondents said they had no previous history of infection. Limitations of serological testing, the questions asked, respondent knowledge and the more traditional concern with respondent veracity are discussed as possible explanations for the observed differences. Study data suggest that use of drug injectors' self-reports to measure infection with sexually transmitted diseases or to validate other measures is a questionable practice. Problems encountered in interpreting study results provide support for more frequent use of experimental or quasi-experimental designs and of multivariate analytic techniques when conducting research on response validity. PMID- 8518719 TI - Discriminating needle exchange attenders from non-attenders. AB - In 1990, approximately 1500 of Glasgow's estimated 9400 injecting drug users attended the city's four needle and syringe exchanges. In the same year, a multisite and citywide strategy was used to interview an estimated 5% sample of the city's injectors using an internationally agreed WHO structured schedule. Of the 503 injectors who participated in the study 54% (n = 272) had made use of exchanges in the last 6 months (including 165 injectors recruited from exchanges), while the remaining 46% (n = 231) had not. Twenty-seven variables were entered into a stepwise discriminant analysis to predict group membership (attenders vs. non-attenders). Fourteen variables emerged in the final discriminant function, which explained 17.3% of the variance between the two groups. Comparison of the model to random classification of cases resulted in a third fewer cases being wrongly assigned. Needle exchange attenders report injecting fewer drugs, less injecting with and passing on of used equipment and greater use of condoms with casual partners, compared to non-attenders. They also had greater knowledge of AIDS and had made and maintained more harm reduction changes, although they were less likely to have received treatment than non attenders. The finding that attenders were less likely to inject with or pass on used needles and syringes is discussed in the context of availability of clean equipment and perception of risk. Variables reflecting lifestyle such as housing, employment and prison experience were not found to have any discriminatory power. PMID- 8518720 TI - Comparing DSM-III-R and ICD-10 substance use disorders. AB - At the present, the DSM-III-R is nearing the final stages of metamorphosis to DSM IV. A series of field trials has been completed which has focused the attention on coverage of the different systems, the impact of social and legal problems on crossing the diagnostic threshold, the importance of subtyping by tolerance and withdrawal, the exclusionary diagnosis of abuse, the duration criterion, and other nosological comparisons. The focus of this Data Note is the comparison of rates between DSM-III, III-R, and both the old and new ICD-10 diagnostic systems, using data from the DSM-IV Substance Use Disorders Field Trials. Especially noteworthy is the inclusion of African Americans, females, and a population with a range of diagnoses and use patterns. Comparisons of DSM-III, III-R and ICD-10 substance use diagnoses among alcohol, nicotine, cannabis, cocaine substance users indicate considerable agreement for dependence but less similarities between systems for abuse and harmful use. These findings suggest that the dependence criteria may be more stable than those chosen to represent abuse and harmful use. More work needs to be done to evaluate the differences and similarities of the diagnostic systems. PMID- 8518721 TI - [The periodicity of the metabolic activity of hepatocytes in culture]. AB - Synchronous changes were found in the intracellular ATP content and in the ratio of "dark" and "light" cells in the monolayer culture of hepatocytes. An attempt has been made to change these ratios by the effect of hormones. The rhythmical processes in the culture are interpreted as a universal cell property. PMID- 8518722 TI - [New data on histological variants of hepatoid cells: the succession of histological variants in the histogenesis of the circumanal glands in the dog]. AB - Studies on the circumanal skin of a three-week-old puppy have shown that, contrary to the adult dogs, sebaceous glands are absent here (although they are well-developed in other skin sites of the puppy). Hepatoid glands accompany every hair follicle; they differ considerably from hepatoid glands of adult dogs. Hepatoid circumanal glands of the three-week old puppy are represented by two histological varieties of this glandular type which are capable of producing hydrophobic lipids, are rather poor in protein, and do not possess cysts--while in adult dogs they are represented by only one variety incapable of synthesizing lipids, extremely rich in protein, possessing numerous cysts. Discussion concerns histogenesis, distribution, and function of certain hepatoid gland varieties which were first described by the authors in their previous publication. PMID- 8518723 TI - [The vagus regulation of the electrical activity of the contractile apparatus in the small intestine of rats under normal and pathological conditions]. AB - The role of parasympathetic division of the vegetal nervous system in regulation of the small intestine motor activity under the normal and pathological conditions was estimated using multifactorial quantitative analysis of the electrical activity of its smooth muscle under the conditions of vagotomy, chronic duodenal ulcer and their combination. Switching off the intestine vagal innervation led to its weakened and altered motor activity, most pronounced on the 3rd and 30th day. Development of the duodenal ulcer is accompanied by the increased motor activity of the intestine with the spasm phenomena, later complemented by disturbed activity of the pacemaker and disturbed myogenic distribution of the electric complex (the most pronounced changes have been noted on the 10th, 40th and 230th day). Vagotomy under the condition of duodenal ulcer normalizes (relaxes) the small intestine motor activity. PMID- 8518724 TI - [DNAse-I inhibition by the chromatin proteins of the brain cells in rats]. AB - The effect of protein extracted from nuclei of brain cells on the reaction of DNA ethidium bromide complex interaction with DNAase I and Bac. subtilis nuclease was studied. The nuclei were isolated from the brain of Wistar male rats weighting 180-200 g. The fluorescence was recorded on a Hitachi MPF-44B spectrofluorimeter. Proteins extracted from the nuclei with 0.6 NaCl substantially inhibited the DNAase I but not Bac. subtilis nuclease activity. Other studied fractions of nuclei lacked the capacity for inhibiting DNAase I. PMID- 8518725 TI - [Changes in the morphology of the thymus and spleen of healthy mice in combined exposure to nitrosomethylurea and immunomodulators]. AB - Changes in the histological structure of thymus and spleen, changes in the area of immune organs occupied by T- and B-lymphocytes and their proliferative activity were studied after the separate and combined treatment of the healthy mice with nitrosomethylurea (NMU), thymalin and Reaferon. NMU alone damaged the lymphoid organs with subsequent incomplete restoration of their histological structure due to pronounced sclerosis. The combined use of NMU and of immunomodulators did not change the NMU acute toxicity but reduced its distant effects. PMID- 8518726 TI - [The ultrastructural and cytointerferometric changes in blood cells induced by endotoxin action]. AB - The results of ultrastructural and cytointerferometric changes of different blood cells in the main target-organ microcirculation are present in the dynamics of endotoxin shock. It is established that the development of endotoxin shock is accompanied by a decrease in dry mass and content of dense substance in red blood cells and leucocytes. Ultrastructural alterations of blood cells have a stable enough character and may be the action of humoral mediator systems or due to direct effects of lipopolysaccharide. Ultrastructural and cytointerferometric changes are discussed in the context of possible receptor-ligand interrelations. PMID- 8518727 TI - Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains. AB - Peptide alpha-amidation is a widespread, often essential posttranslational modification shared by many bioactive peptides and accomplished by the products of a single gene encoding a multifunctional protein, peptidylglycine alpha amidating monooxygenase (PAM). PAM has two catalytic domains that work sequentially to produce the final alpha-amidated product peptide. Tissue-specific alternative splicing can generate forms of PAM retaining or lacking a domain required for the posttranslational separation of the two catalytic activities by endoproteases found in neuroendocrine tissue. Tissue-specific alternative splicing also governs the presence of a transmembrane domain and generation of integral membrane or soluble forms of PAM. The COOH-terminal domain of the integral membrane PAM proteins contains routing information essential for the retrieval of PAM from the surface of endocrine and nonendocrine cells. Tissue specific endoproteolytic processing can generate soluble PAM proteins from integral membrane precursors. Soluble PAM proteins are rapidly secreted from stably transfected nonneuroendocrine cells but are stored in the regulated secretory granules characteristic of neurons and endocrine cells. PMID- 8518728 TI - The Escherichia coli adenylyl cyclase complex: stimulation by GTP and other nucleotides. AB - Escherichia coli cells permeabilized by treatment with low concentrations of toluene contain an adenylyl cyclase activity that can be stimulated 3.6-7.6-fold by GTP. The stimulatory effect of GTP is maximal at concentrations of the nucleotide in the physiological range (above 0.7 mM). Studies of the dependence of velocity on substrate (ATP) concentration indicate that the velocity vs. substrate plots are sigmoid in the absence of GTP but hyperbolic in the presence of GTP, suggesting an allosteric regulatory site that can be occupied by either ATP or GTP. Replacement of ATP by AMPPNP as substrate results in velocity vs. substrate plots that are hyperbolic in the absence or presence of GTP, although GTP increases the Vmax by a factor of 2.2; these findings indicate that AMPPNP specifically occupies the substrate site and GTP exclusively occupies the regulatory site. A test of the capacity of other guanine nucleotides to stimulate adenylyl cyclase activity showed that 2'-deoxy-GTP was almost as effective as GTP, but that GDP, GMP, ppGpp, and 3',5'-cGMP were not stimulatory effectors; GTP gamma-S and GMPPNP stimulated adenylyl cyclase activity but to a lesser degree than did GTP. In addition to the previous indication that ATP can occupy the regulatory site on adenylyl cyclase, it was found that CTP and UTP were potent stimulators. Thus, all the naturally occurring RNA precursor nucleoside triphosphates are capable of stimulating adenylyl cyclase activity. In contrast, PPPi inhibits adenylyl cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518729 TI - Tautomeric states of the active-site histidines of phosphorylated and unphosphorylated IIIGlc, a signal-transducing protein from Escherichia coli, using two-dimensional heteronuclear NMR techniques. AB - IIIGlc is an 18.1-kDa signal-transducing phosphocarrier protein of the phosphoenolpyruvate:glycose phosphotransferase system from Escherichia coli. The 1H, 15N, and 13C histidine ring NMR signals of both the phosphorylated and unphosphorylated forms of IIIGlc have been assigned using two-dimensional 1H-15N and 1H-13C heteronuclear multiple-quantum coherence (HMQC) experiments and a two dimensional 13C-13C-1H correlation spectroscopy via JCC coupling experiment. The data were acquired on uniformly 15N-labeled and uniformly 15N/13C-labeled protein samples. The experiments rely on one-bond and two-bond J couplings that allowed for assignment of the signals without the need for the analysis of through-space (nuclear Overhauser effect spectroscopy) correlations. The 15N and 13C chemical shifts were used to determine that His-75 exists predominantly in the N epsilon 2 H tautomeric state in both the phosphorylated and unphosphorylated forms of IIIGlc, and that His-90 exists primarily in the N delta 1-H state in the unphosphorylated protein. Upon phosphorylation of the N epsilon 2 nitrogen of His 90, the N delta 1 nitrogen remains protonated, resulting in the formation of a charged phospho-His-90 moiety. The 1H, 15N, and 13C signals of the phosphorylated and unphosphorylated proteins showed only minor shifts in the pH range from 6.0 to 9.0. These data indicate that the pK alpha values for both His-75 and His-90 in IIIGlc and His-75 in phospho-IIIGlc are less than 5.0, and that the pK alpha value for phospho-His-90 is greater than 10. The results are presented in relation to previously obtained structural data on IIIGlc, and implications for proposed mechanisms of phosphoryl transfer are discussed. PMID- 8518730 TI - Thermal unfolding of staphylococcal nuclease and several mutant forms thereof studied by differential scanning calorimetry. AB - The effects of eight mutations on the thermodynamics of the reversible thermal unfolding of staphylococcal nuclease have been determined over a range of pH and protein concentration by means of differential scanning calorimetry. Variation of the protein concentration was included in our study because we found a significant dependence of the thermodynamics of protein unfolding on concentration. Values for the change in the standard free energy of unfolding, delta delta G0d, produced by the mutations in the pH range 5.0-7.0 varied from 1.9 kcal mol-1 (apparent stabilization) for H124L to -2.8 kcal mol-1 (apparent destabilization) for L25A. As has been observed in numerous other cases, there is no correlation in magnitude or sign between delta delta G0d and the corresponding values for delta delta Hd and T delta delta S0d, the latter quantities being in most cases much larger in magnitude than delta delta G0d. This fact emphasizes the difficulty in attempting to correlate the thermodynamic changes with structural changes observed by X-ray crystallography. PMID- 8518731 TI - Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of F22A, Y23A, N43G, and F45A. AB - Crystal structures of four mutants of bovine pancreatic trypsin inhibitor (F22A, Y23A, N43G, and F45A), engineered to alter their stability properties, have been determined. The mutated residues, which are highly conserved among Kunitz-type inhibitors, are located in the rigid core of the molecule. Replacement of the partially buried bulky residues of the wild-type protein with smaller residues resulted in crevices open to the exterior of the molecule. The overall three dimensional structure of these mutants is very similar to that of the wild-type protein and only small rearrangements are observed among the atoms lining the crevices. PMID- 8518733 TI - A model for the calmodulin-peptide complex based on the troponin C crystal packing and its similarity to the NMR structure of the calmodulin-myosin light chain kinase peptide complex. AB - In the crystal structure of troponin C, the holo C-domain is bound in a head-to tail fashion to the A-helix of the apo N-domain of a symmetry-related molecule. Using this interaction, we have proposed a model for the calmodulin-peptide complex. We find that the interaction of the C-domain with the A-helix is similar to that observed in the NMR structure of the calmodulin-myosin light chain kinase (MLCK) peptide complex. This similarity in binding has enabled us to make a precise sequence alignment of the target peptides in the calmodulin-binding cleft and to rationalize the amino acid sequence-dependent binding strengths of various peptides. Our model differs from that proposed by Strynadka and James (Proteins Struct. Funct. Genet. 7, 234-248, 1990) in that the peptides are rotated by 100 degrees in the calmodulin binding cleft. PMID- 8518732 TI - Crystal structure of deoxygenated Limulus polyphemus subunit II hemocyanin at 2.18 A resolution: clues for a mechanism for allosteric regulation. AB - The crystal structure of Limulus polyphemus subunit type II hemocyanin in the deoxygenated state has been determined to a resolution of 2.18 A. Phase information for this first structure of a cheliceratan hemocyanin was obtained by molecular replacement using the crustacean hemocyanin structure of Panulirus interruptus. The most striking observation in the Limulus structure is the unexpectedly large distance of 4.6 A between both copper ions in the oxygen binding site. Each copper has approximate trigonal planar coordination by three histidine N epsilon atoms. No bridging ligand between the copper ions could be detected. Other important new discoveries are (1) the presence of a cis-peptide bond between Glu 309 and Ser 310, with the carbonyl oxygen of the peptide plane hydrogen bonded to the N delta atom of the copper B ligand His 324; (2) localization of a chloride-binding site in the interface between the first and second domain; (3) localization of a putative calcium-binding site in the third domain. Furthermore, comparison of Limulus versus Panulirus hemocyanin revealed considerable tertiary and quaternary rigid body movements, although the overall folds are similar. Within the subunit, the first domain is rotated by about 7.5 degrees with respect to the other two domains, whereas within the hexamer the major movement is a 3.1 degrees rotation of the trimers with respect to each other. The rigid body rotation of the first domain suggests a structural mechanism for the allosteric regulation by chloride ions and probably causes the cooperative transition of the hexamer between low and high oxygen affinity states. In this postulated mechanism, the fully conserved Phe49 is the key residue that couples conformational changes of the dinuclear copper site into movements of the first domain. PMID- 8518734 TI - Prediction of the three-dimensional structures of the biotinylated domain from yeast pyruvate carboxylase and of the lipoylated H-protein from the pea leaf glycine cleavage system: a new automated method for the prediction of protein tertiary structure. AB - A new, automated, knowledge-based method for the construction of three dimensional models of proteins is described. Geometric restraints on target structures are calculated from a consideration of homologous template structures and the wider knowledge base of unrelated protein structures. Three-dimensional structures are calculated from initial partly folded states by high-temperature molecular dynamics simulations followed slow cooling of the system (simulated annealing) using nonphysical potentials. Three-dimensional models for the biotinylated domain from the pyruvate carboxylase of yeast and the lipoylated H protein from the glycine cleavage system of pea leaf were constructed, based on the known structures of two lipoylated domains of 2-oxo acid dehydrogenase multienzyme complexes. Despite their weak sequence similarity, the three proteins are predicted to have similar three-dimensional structures, representative of a new protein module. Implications for the mechanisms of posttranslational modification of these proteins and their catalytic function are discussed. PMID- 8518735 TI - Modeling the structure of Pyrococcus furiosus rubredoxin by homology to other X ray structures. AB - The three-dimensional structure of rubredoxin from the hyperthermophilic archaebacterium, Pyrococcus furiosus, has been modeled from the X-ray crystal structures of three homologous proteins from Clostridium pasteurianum, Desulfovibrio gigas, and Desulfovibrio vulgaris. All three homology models are similar. When comparing the positions of all heavy atoms and essential hydrogen atoms to the recently solved crystal structure (Day, M. W., et al., 1992, Protein Sci. 1, 1494-1507) of the same protein, the homology model differ from the X-ray structure by 2.09 A root mean square (RMS). The X-ray and the zinc-substituted NMR structures (Blake, P. R., et al., 1992b, Protein Sci. 1, 1508-1521) show a similar level of difference (2.05 A RMS). On average, the homology models are closer to the X-ray structure than to the NMR structures (2.09 vs. 2.42 A RMS). PMID- 8518736 TI - Investigations of the thermostability of rubredoxin models using molecular dynamics simulations. AB - The affects of differences in amino acid sequence on the temperature stability of the three-dimensional structure of the small beta-sheet protein, rubredoxin (Rd), was revealed when a set of homology models was subjected to molecular dynamics simulations at relatively high temperatures. Models of Rd from the hyperthermophile, Pyrococcus furiosus (Pf), an organism that grows optimally at 100 degrees C, were compared to three mesophilic Rds of known X-ray crystal structure. Simulations covering the limits of known Rd thermostabilities were carried out at temperatures of 300 K, 343 K, 373 K, and 413 K. They suggest that Rd stability is correlated with structural dynamics. Because the dynamic behavior of three Pf Rd models was consistently different from the dynamic behavior of the three mesophilic Rd structures, detailed analysis of the temperature-dependent dynamic behavior was carried out. The major differences between the models of the protein from the hyperthermophile and the others were: (1) an obvious temperature dependent transition in the mesophilic structures not seen with the Pf Rd models, (2) consistent AMBER energy for the Pf Rd due to differences in nonbonded interaction terms, (3) less variation in the average conformations for the Pf Rd models with temperature, and (4) the presence of more extensive secondary structure for the Pf Rd models. These unsolvated dynamics simulations support a simple, general hypothesis to explain the hyperthermostability of Pf Rd. Its structure simplifies the conformational space to give a single minimum accessible over an extreme range of temperatures, whereas the mesophilic proteins sample a more complex conformational space with two or more minima over the same temperature range. PMID- 8518737 TI - Are hepatocyte growth factor-like protein and macrophage stimulating protein the same protein? PMID- 8518738 TI - A trefoil domain in the major rabbit zona pellucida protein. PMID- 8518739 TI - Reminiscences from a life in protein physical chemistry. PMID- 8518740 TI - Special issue: Cellular aspects related to peroxisome. Proceedings of FEBS satellite International Meeting. Dijon, France, April 28-29, 1993. PMID- 8518741 TI - Peroxisome proliferators as inducers and substrates of UDP glucuronosyltransferases. AB - Peroxisome proliferators, despite their chemically unrelated structures, share the common property of being able to stimulate the glucuronidation of bilirubin in rodents and, probably, also in man. The aryloxycarboxylic acids (clofibric acid, fenofibrate, bezafibrate, ciprofibrate), tiadenol and probucol, all of which have hypolipidemic properties, as well as the fatty acid-like perfluorodecanoic acid all enhanced the expression of the UDP glucuronosyltransferase (UGT) form involved in the conjugation of the pigment. This induction is manifested by an increase in the mRNA species encoding the protein with a subsequent increase in the neosynthesis of the corresponding protein in the endoplasmic reticulum. The induction process is concomitant with that of cytochrome P-450-IVA1 and cytosolic epoxide hydrolase, which, like bilirubin UGT, are mainly involved in the metabolism of endogenous substrates. With a series of carboxylic acids related to clofibric acid, it was possible to demonstrate that induction was mediated via specific interactions based on the physicochemical properties of the inducers. Until now, the molecular basis of induction of bilirubin UGT is not known. The peroxisome poliferators that possess a carboxyl group are good substrates of UGT, especially in man. The acylglucuronides formed are known for their instability and reactivity which could contribute to the toxicity encountered in some patients treated with the drugs. There is convincing evidence that UGT bilirubin does not catalyze the glucuronidation of these substances even if the two types of substrate form acylglucuronides. PMID- 8518743 TI - The integration of investigative toxicology in the drug discovery process. AB - Integrating toxicology early in the drug discovery process adds value by providing the earliest possible identification of a compound's potential for toxicological and pathological effects relevant to intended clinical use. With this approach true 'lead' candidates, with a high probability of clinical success, are identified and advanced while reducing effort and resources expended on compounds without the requisite therapeutic index. Resources are focussed on the speed of getting a discovery 'lead' into early clinical development, defining the mechanisms of observed preclinical toxicity and their relevance to human use, and developing early safety data with in vitro test systems ahead of in vivo systems where possible, thus reducing animal use. PMID- 8518742 TI - Response of genetically obese Zucker rats to ciprofibrate, a hypolipidemic agent, with peroxisome proliferation activity as compared to Zucker lean and Sprague Dawley rats. AB - Genetically obese Zucker (fa/fa) rats were used as an experimental model to study the effects of hypolipidemic agents on peroxisome proliferation; comparison was made with Zucker lean phenotype (Fa/-) and Sprague-Dawley strain/phenotype. The pharmacokinetics of a single administration of ciprofibrate (1 or 3 mg/kg), appeared to be similar in all strains/phenotypes. After a 2-week oral administration at the same dosages, there were dosage-related increases in hepatocellular peroxisomal yield and in the hepatic enzymes' cyanide-insensitive acyl-CoA oxidase and catalase. The peroxisomal yield was less increased in Zucker than in Sprague-Dawley rats, while the enzyme activities were similarly increased. Although the absolute specific activity of microsomal omega-lauryl hydroxylase (cytochrome P4504A1) was lower in Zucker rats, it was increased more in this strain than in Sprague-Dawley rats in response to drug exposure. The hypolipidemic effect (cholesterol and triglyceride reduction) was more pronounced in Zucker obese rats. Based on biochemical and morphological results, no major differences between strains/phenotypes in terms of peroxisome proliferation were observed following a 2-week administration of ciprofibrate. PMID- 8518744 TI - Peroxisome proliferators and cellular signaling pathways. A review. AB - In a variety of biological systems, the cellular response to an extracellular stimulus is mediated by a complex cascade of biochemical signals transduced from the cellular membrane to the specific part(s) of the cell where the response(s) occur(s). The signal transduction pathways do form a matrix of several reactions involving increased intracellular free Ca2+ levels, activation of Na+/H+ exchange, stimulation of phosphatidylinositol turnover, activation of protein kinase C and increased transcription of several cellular proto-oncogenes. Each of them is subject to modulation at many levels, and is also susceptible to deregulation during chemically-induced carcinogenesis. It is the aim of this short review to give an insight into the complexity of this system which may mediate the effects induced in hepatocytes by peroxisome proliferators or may, upon chronic exposure, be altered by some of them. PMID- 8518745 TI - Molecular chaperones and the biogenesis of mitochondria and peroxisomes. AB - A review of the proteinaceous machinery involved in protein sorting pathways and protein folding and assembly in mitochondria and peroxisomes is presented. After considering the various sorting pathways and targeting signals of mitochondrial and peroxisomal proteins, we make a comparative dissection of the protein factors involved in: i) the stabilization of cytosolic precursor proteins in a translocation competent conformation; ii) the membrane import apparatus of mitochondria and peroxisomes; iii) the processing of mitochondrial precursor proteins, and the eventual processing of certain peroxisomal precursor, in the interior of the organelles; and iv) the requirement of molecular chaperones for appropriate folding and assembly of imported proteins in the matrix of both organelles. Those aspects of mitochondrial biogenesis that have developed rapidly during the last few years, such as the requirement of molecular chaperones, are stressed in order to stimulate further parallel investigations aimed to understand the origin, biochemistry, molecular biology and pathology of peroxisomes. In this regard, a brief review of findings from our group and others is presented in which the role of the F1-ATPase alpha-subunit is pointed out as a molecular chaperone of mitochondria and chloroplasts. In addition, data are presented that could question our previous indication that the immunoreactive protein found in the rat liver peroxisomes is due to the presence of the F1 ATPase alpha-subunit. PMID- 8518746 TI - Transferrin gene as a model for liver-specific gene expression. AB - The results obtained in the recent years have led to an understanding of the mechanisms controlling liver-specific gene expression. They indicate that this expression needs an appropriate combination of hepatocyte and ubiquitous transcriptional factors, interacting with cis-acting DNA elements, in a characteristic manner for each gene. However, a number of important questions about liver organogenesis and specific cell differentiation remain to be answered. PMID- 8518747 TI - Peroxisome through cell differentiation and neoplasia. AB - Peroxisomes are essential in cellular metabolism as their dysgenesis or defects in single enzymes or impairment of multiple peroxisomal enzymatic functions have been found in several inherited metabolic diseases with serious clinical sequelae. The assembly and formation of these cytoplasmic organelles constitute a major and intriguing research topic. In the present study the biogenesis of peroxisomes and the developmental patterns of their enzymes have been reviewed during embryonic and/or post-embryonic ontogenesis of lower (amphibians) and higher (avians, mammals) vertebrates. In developing vertebrates, epithelial cell differentiation is accompanied by increases in frequency and size of peroxisomes. The tissue-specific expression of peroxisomal enzymes contributes substantially to the biochemical maturation of epithelial cells. The relationship between biogenesis of peroxisomes, expression of peroxisomal enzymes and structural and functional cellular phenotype has also been investigated in differentiating epithelial cells along the crypt-villus axis of the adult rat intestine. Cytochemical studies at the ultrastructural level have provided evidence that peroxisomes are already present in proliferating cells of the intestinal crypt region before they begin to differentiate. Migration and differentiation of intestinal epithelial cells from crypt to villus compartments are marked by significant increases in number and size of catalase-positive structures. Increasing activity gradients from crypt to surface areas are found for the peroxisomal oxidases examined (enzymes of the peroxisomal beta-oxidation system, D-amino acid oxidase and polyamine oxidase). Thus, peroxisomes are more and more involved in oxidative metabolic pathways as intestinal epithelial cells differentiate. Finally, we have analyzed the peroxisomal behaviour in human neoplastic epithelial cells. The presence of peroxisomes has been cytochemically revealed in human breast and colon carcinomas. Peroxisomal enzyme specific activities are significantly lower in human breast and colon carcinomas than in the adjacent healthy mucosa. Furthermore, a relationship is found between the specific activities of some peroxisomal enzymes and the histological tumour grades. PMID- 8518748 TI - Proteins and enzymes of the peroxisomal membrane in mammals. AB - Proteins of the peroxisomal membrane can be schematically divided into two groups, one being made up of more or less characterized proteins with generally unknown functions and the other consisting of enzyme activities of which the corresponding proteins have not been characterized. In the present report, these proteins and enzymes are described with the addition of unpublished results regarding their induction by peroxisome proliferators at the post-transcriptional level. Integral membrane proteins (IMPs) can be isolated using an alkaline solution of sodium carbonate. A dozen of preponderant IMPs can be seen on sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the major band corresponds to a 70 kDa IMP, of which the corresponding rat cDNA is known. Some IMPs have been characterized by immunoblot analysis. Recently, a cDNA has been cloned for a peroxisome assembly factor (35 kDa IMP). Functions have also been proposed for some IMPs but are not yet firmly settled. Some IMPs (450/520, 70 and 26 kDa) are strongly induced by peroxisome proliferators. Our results extend to cipro- and fenofibrate the observation that the 70 kDa IMP mRNA level is strongly increased in di(2-ethylhexyl)phtalate-treated rats. All the enzyme activities associated with the peroxisomal membrane are involved in lipid metabolism: activation of substrates (fatty acids), ether lipid biosynthesis, and formation of precursors (fatty alcohols). It is believed that the same long-chain acyl-CoA synthetase occurs in the peroxisome as well as in the outer mitochondrial membrane and the endoplasmic reticulum. However, two highly homologous but different cDNAs encoding rat liver and brain long-chain acyl-CoA synthetases have been isolated recently. Evidence has been accumulated for a distinct synthetase that specifically activates very-long chain fatty acids. The first two steps of ether lipid biosynthesis require dihydroxyacetone-phosphate (DHAP) acyltransferase and alkyl-DHAP synthetase, the active sites of which are located on the inner surface of the membrane. In contrast, the catalytic site of the acyl/alkyl-DHAP reductase, which generates sn-1-alkyl-glycerol-3-phosphate, is located on the outer surface. Long-chain fatty alcohols, which are obligate precursors of ether lipids and wax esters, are biosynthetized by the reduction of the corresponding acyl-CoAs via the action of an acyl-CoA reductase. Peroxisome proliferators do not appear to stimulate these enzyme activities specifically. However, we report that feno- and ciprofibrate treatments increase six-fold the palmitoyl-CoA synthetase mRNA level in the rat liver. PMID- 8518749 TI - Regio- and stereo-selectivity in the induction of peroxisome proliferation by substituted hexanoic acids. AB - Quantitative structure-activity relationship is an effective tool in order to predict drug potency. A similar approach is actually developed for peroxisome proliferation induced by substituted carboxylic acids issued from plasticizer metabolism in rats. The study is focused on acids found in rat urine after adipic diester dosings. Size, location of the substituted group and length of the chain have been studied. 3-D structure has also been taken in account for 2-ethyl hexanoic acids. The results obtained so far demonstrate that peroxisome proliferation potencies of the considered acids are modified according structure changes. At this time location of the group along the chain appears to be a predominant factor. PMID- 8518750 TI - Occurrence of plasmids in black-pigmented gram-negative anaerobes. AB - Black-pigmented Gram-negative anaerobes are causative agents of pyogenic infections and are closely linked to various forms of periodontal diseases. Whereas many studies have shown a high incidence of plasmids in intestinal Bacteroides spp., there have been only a few reports of plasmid analyses in pigmented Gram-negative anaerobes. According to previous reports and confirmed in this study, plasmids can be present in Porphyromonas asaccharolytica, Prevotella intermedia, Pr. melaninogenica, and B. levii but have not been detected in P. gingivalis or other black-pigmented species. There were no correlations between plasmids and phenotypes such as resistance to antibiotics or bacteriocinogenicity. The highest carriage rate was found in isolates from cases of chronic otitis media, but the relationship between this site of infection and a high incidence of plasmids could be incidental. The size of plasmids ranged from 1.5 to 29 MDa. Plasmids with molecular weight > 10 MDa were described for the first time in these organisms. Repeated plasmid analyses showed that the plasmid patterns were generally stable. PMID- 8518751 TI - Classification of black-pigmented anaerobes by pyrolysis mass spectrometry (PMS) and conventional tests (CTs). AB - Clinical (66: dental 53; vaginal 4; wound 9) and reference (5*) strains of pigmented Gram-negative anaerobic bacilli were examined in pyrolysis mass spectrometry (PMS) and conventional tests (CTs). The strains were identified in CTs as: Prevotella intermedia (48*); Pr. melaninogenica (1); Pr. corporis (7); Porphyromonas asaccharolytica (12*); P. endodontalis (1*) and P. gingivalis (2*). Numerical classification based on CTs resolved five clusters comprising strains identified as (I) Pr. corporis, (II) Pr. melaninogenica, (III) Pr. intermedia, (IV) P. gingivalis and (V) P. asaccharolytica and P. endodontalis. Numerical classification based on PMS showed a similar division, with decreasing homogeneity in the order Pr. intermedia, Pr. corporis, P. asaccharolytica, in agreement with the ordering of homogeneity for these species in CTs. PMS clusters corresponding the Porphyromonas spp. were clearly distinct from those of Prevotella spp. PMS and CT classifications disagreed on cluster membership for only six of the strains. PMS identification from blind challenge sets agreed with conventional identification for 64 of 67 strains. PMID- 8518752 TI - Hydrolytic enzymes liberated by black-pigmented gram-negative anaerobes. PMID- 8518753 TI - Host factors predisposing to anaerobic infections. AB - Factors that predispose to infection in general, of course, may predispose to infection with anaerobes. Included in this category are diabetes mellitus, neutropenia, hypogammaglobulinaemia, malignancy, splenectomy, collagen vascular disease, cytotoxic drug therapy, corticosteroid therapy and other immunosuppression. However, even with these situations there may be certain, more specific, associations: anaerobic cholecystitis and anaerobic osteomyelitis in diabetics, neutropenic colitis, and the increased incidence of local anaerobic infections associated with carcinoma of the lung, colon and uterus. Conditions that lead to decreased redox potential more specifically predispose to infection with anaerobes. Included in this category are obstruction and stasis, tissue anoxia, tissue destruction, vascular insufficiency, prior aerobic infection, burns, foreign body implantation, and calcium salts in a wound (in association with fractures). Other specific clinical situations that predispose to anaerobic infections include leukaemia; oral, gastrointestinal, and female pelvic surgery; trauma at other sites; childbirth; aspiration pneumonia; human and animal bites; and therapy with agents with poor activity against anaerobes (e.g. aminoglycosides, quinolones). AIDS patients appear to be predisposed to severe periodontal disease and its complications. PMID- 8518754 TI - Interactions between black-pigmented gram-negative anaerobes and other species which may be important in disease development. PMID- 8518755 TI - Black-pigmented gram-negative anaerobes in periodontitis. AB - Black-pigmented Gram-negative anaerobes have been associated with periodontal disease and tooth loss since they were first isolated by Burdon in 1928. Porphyromonas gingivalis, which is usually not isolated from children, adolescents or adults with no periodontal breakdown, has been recognized as one of the most important periodontopathogens. Its presence is strongly correlated with deep periodontal pockets, which are assumed to be its main habitat. Correlations have been shown also with attachment loss, clinical inflammation and serum antibody levels, indicating an aetiological role in the periodontal disease. Their pathogenicity in animal models resembling periodontal disease is documented. They are frequently isolated from periodontal abscesses. The relationship between Prevotella intermedia and periodontal disease is not clear. It is frequently isolated from advanced periodontitis, often as the only black pigmented Gram-negative anaerobic species; however, the prevalence in adults with no periodontal breakdown is high. It is found frequently in periodontal abscesses and in acute necrotizing and ulcerative gingivitis. Serogroup I is found predominantly in deep periodontal pockets, whereas all serogroups (I-III) are found in shallow pockets and gingivitis. No conclusive difference in pathogenicity between serogroups has been found. Pr. melaninogenica, Pr. denticola and Pr. loescheii are frequently found in the gingival crevice in preschool children and other age groups with gingivitis, but are seldom found in deep periodontal pockets. PMID- 8518756 TI - Pigmented Prevotella species in the periodontally healthy oral cavity. AB - Pigmented Prevotella spp. have been connected with oral infections as well as being part of the healthy gingival flora. The aim of this study was to determine the presence of pigmented Prevotella spp. in saliva and gingival crevice samples from periodontally healthy adults. Twelve Caucasian female subjects (mean age 28 years, range 21-36 years) with no pockets > or = 4 mm, nor bleeding after probing were selected for this study. Paraffin-stimulated saliva was collected first; then, a pooled subgingival bacterial sample was taken with a sterile curette from mesiobuccal surfaces of all first molars. The samples were inoculated on to non selective and selective media and incubated anaerobically. The most frequent species isolated were Pr. melaninogenica, Pr. intermedia and Pr. loescheu, found in 11, ten and nine subjects, respectively. The mean percentage of the total cultivable anaerobic microflora in salivary/subgingival samples were 14.7/0.6 for Pr. melaninogenica, 3.1/5.3 for Pr. intermedia and 2.6/1.2 for Pr. loescheii. Pr. denticola was found in one saliva sample and Pr. corporis, in two subgingival samples only. The number of different pigmented Prevotella spp. in the same mouth was 2-4 (mean 2.75). In conclusion, Pr. melaninogenica, Pr. intermedia and Pr. loescheii seem to be common microorganisms in the periodontally healthy oral cavity. PMID- 8518757 TI - Porphyromonas-like gram-negative rods in naturally occurring periodontitis in dogs. AB - A total of 259 Gram-negative Porphyromonas-like rods isolated from subgingival plaque samples of 16 family-owned dogs with naturally occurring periodontitis were characterized phenotypically by biochemical reactions, metabolic end products and enzymatic activities (API-ZYMTM, RoscoTM). Four distinct groups were found. Group A isolates (63) were asaccharolytic, lipase negative, trypsin positive and produced phenylacetic acid (PAA) from peptone-yeast extract glucose broth. Unlike P. gingivalis strains they were catalase positive. Group B isolates (42) differed from those of group A by a positive lipase reaction and from those of group D by failing to ferment sugars. Group C isolates (88) were asaccharolytic and did not produce PAA. They were alpha-fucosidase, N-acetyl-beta glucosaminidase (beta-NAG) and trypsin negative, resembling P. endodontalis, but unlike human isolates, they were catalase positive. Subgroup C.1 isolates (6) differed from those of parent group C by producing minor amounts of PAA, and subgroup C.2 isolates (12) were beta-NAG positive. Group D isolates (46) were weakly fermentative, lipase, catalase and trypsin positive, and produced PAA. They resembled the B (P.) salivosus type strain which, in our hands, fermented weakly glucose, lactose and mannose. Two isolates could not be assigned to any of the previous groups. PMID- 8518758 TI - Black-pigmented gram-negative anaerobes in endodontic infections. AB - Necrotic dental root canal infections are polymicrobial infections dominated by anaerobic bacteria. The number of different species in one canal is usually low, approx. 4-7 species. The species isolated most frequently belong to the genera Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Eubacterium and Streptococcus. The frequency of isolation of black-pigmented Gram-negative anaerobes in endodontic infections varies from 25% to > 50%. Pr. intermedia is the most commonly found pigmented species, followed by Pr. denticola and two Porphyromonas species, P. gingivalis and P. endodontalis. Several studies have shown that P. gingivalis and P. endodontalis are closely related to the presence of acute symptoms in endodontic infections, whereas other black-pigmented Gram negative anaerobes are not. However, several other species may also be involved in acute infections. Moreover, Porphyromonas species have occasionally been isolated from cases with no symptoms. Although Porphyromonas spp. are clearly related to symptoms at the beginning of therapy, they are not important for the prognosis of the treatment. PMID- 8518759 TI - The presence of black-pigmented gram-negative anaerobes in the oral cavity of edentulous subjects. AB - The aim of this study was to investigate whether black-pigmented Gram-negative anaerobes are part of the indigenous oral flora of edentulous subjects with or without dentures. Group I consisted of 11 subjects with dentures (mean age 63.6 years, range 52-75) and Group II consisted of 39 subjects with complete dentures in both jaws (mean age 59.3 years, range 37-80). Two microbial samples for microbiological examination were taken from each subject. One of them was from the dorsum of the tongue and the other was from saliva. Black-pigmented Gram negative anaerobes > 10(7) cfu/ml were found in both samples. In 50 edentulous subjects, they were found more commonly from tongue (40%) than from saliva (26%). None of the subjects had Porphyromonas gingivalis. There was no statistically significant difference (P > 0.05) between the presence of black-pigmented Gram negative anaerobes on tongue and in saliva in the two groups. Our results suggested that high levels of black-pigmented Gram-negative anaerobes may belong to the indigenous oral flora in edentulous mouths with or without dentures. PMID- 8518760 TI - Black-pigmented gram-negative anaerobes in genito-urinary tract and pelvic infections. AB - Black-pigmented Gram-negative anaerobes are part of the normal vaginal flora and contribute to a range of superficial and deep genital infections. Prevotella melaninogenica is found in moderate numbers (10(4-6) cfu/g) in healthy women; the numbers and detection rates increase in anaerobic vaginosis (where it may be a significant contributor to changed microbial metabolic activity that gives the signs and symptoms of this condition) and in other vaginal infective conditions. Pr. melaninogenica is also part of the mixed flora in deep pelvic infections: endometritis, post-partum and post-abortal uterine infections; salpingitis and tubo-ovarian abscesses; PID and pelvic abscesses. Porphyromonas asaccharolytica is probably not a vaginal commensal, but may be isolated from patients with vaginal or pelvic disease. It is more specifically associated with superficial abscesses (e.g. Bartholin's abscess) and ulcers of the genitalia and perineum. P. asaccharolytica was the commonest species isolated from men with genital ulcers of various primary causes and ranging in severity from superficial balanitis/balanoposthitis to synergic gangrene. PMID- 8518761 TI - Antibiotic susceptibilities of black-pigmented gram-negative anaerobes. PMID- 8518762 TI - Antimicrobial activities of black-pigmented gram-negative anaerobes. AB - The antimicrobial activities of Prevotella intermedia and Porphyromonas gingivalis isolates were tested against other species of Gram-positive and Gram negative anaerobes as well as against each other. Generally, Pr. intermedia possessed significantly higher antimicrobial activity than P. gingivalis. The strongest activity of P. gingivalis towards Gram-negative anaerobes was directed against Pr. intermedia. Cross-sensitivity between both species was observed with strains from different lesions. Antimicrobial activity towards strains of the same species was detected only with Pr. intermedia. No correlations were found between plasmid content and antimicrobial activity. It was concluded that the inhibitory potency of Pr. intermedia could be one reason for the high proportion of black-pigmented Gram-negative anaerobes in the subgingival flora of periodontitis lesions. PMID- 8518763 TI - Resistance to various chemotherapeutic agents of Bacteroides spp. isolated from clinical specimens in Istanbul. PMID- 8518764 TI - The importance of black-pigmented gram-negative anaerobes in human infections. AB - Black-pigmented Gram-negative anaerobic rods are found on mucosal surfaces as indigenous flora. With mucosal damage due to disease, trauma or surgery, these organisms may invade tissues and set up infection. Other important factors determining whether or not infection results include 'inoculum' size, synergy with other organisms and production of virulence factors that include capsules, lipopolysaccharide, attachment factors, proteases, collagenase, neuraminidase, and phospholipase A; also, they may have fibrinolytic and anti-phagocytic activity and may degrade complement and IgG and IgM. Pigmented anaerobes are found in all types of infections including such serious infections as bacteraemia, endocarditis, intracranial abscess, necrotizing pneumonia and necrotizing fasciitis, generally as part of a mixed infecting flora, and they play a key role in experimental mixed infections. They dominate or are prominent in infections involving organisms originating in the oropharynx, such as central nervous system, head and neck, dental and pleuropulmonary infections. Therapy of infections involving pigmented anaerobes includes surgery plus antimicrobial agents; a significant percentage of strains produce beta-lactamase. Much remains to be done to determine the relative importance of the various taxa of black pigmented Gram-negative anaerobes and of the different virulence factors produced by them. PMID- 8518765 TI - Proposal of a new species Prevotella nigrescens sp. nov. among strains previously classified as Pr. intermedia. PMID- 8518766 TI - Positive effects of increased nurse support for male patients after acute myocardial infarction. AB - The effect of increased nurse support on patients below 70 years of age attending an out-patient clinic following acute myocardial infarction was evaluated. Patients who saw a nurse 14 days after discharge (n = 56) were compared to a control group (n = 47) who, following the ordinary routines, were first seen 8 weeks after discharge. Increased nurse support had positive effects on psychosocial variables such as depressive feelings, expected quality of life in the future, and satisfaction with contact with the staff. However, no effects were found on any of the cardiac variables. Patients in the intervention group showed a decrease in depressive feelings during the 8 weeks follow-up period, whereas there was an increase for the control group. The patients in the intervention group also tended to have a better belief in the future compared to the control group. Patients in the intervention group were more satisfied with the staff contact than were the control group. PMID- 8518767 TI - Testing the EORTC Quality of Life Questionnaire on cancer patients with heterogeneous diagnoses. AB - This study aimed to contribute to the validation of the 30-item Quality of Life Questionnaire developed by the European Organization for Research and Treatment of Cancer Study Group (EORTC QLQ-C30). The sample consisted of 177 cancer patients with heterogeneous diagnoses. A series of scales representing various dimensions of quality of life were tested, including those proposed by the EORTC Study Group. Mokken's non-parametric latent trait model for unidimensional scaling was used as the basic scaling procedure. This model gives coefficients of scalability in addition to reliability coefficients. In terms of scalability measured by Loevinger's H, all EORTC Study Group scales, except the cognitive functioning scale were found to be quite satisfactory. The cognitive functioning scale and the role functioning scale were below the satisfactory level in terms of reliability (internal consistency). In total, our study strengthens the external validity of the EORTC QLQ-C30 and confirms that it may be used on cancer patients with various diagnoses. PMID- 8518768 TI - The effect of a weighted vest on perceived health status and bone density in older persons. AB - To assess the effect of an exercise intervention using a weighted vest on perceived health status and bone density in older persons, we enrolled 36 seniors in a randomized controlled trial. The vest-use group met weekly for 1 h for a low level exercise class. They wore a weighted vest during the class and as tolerated at home. The discussion controls met for 1 h weekly. At baseline and follow-up (20 weeks), subjects completed a questionnaire that included the 20 item MOS Short-Form Health Survey, Multidimensional Health Locus of Control Scale, and Philadelphia Geriatric Center Morale Scale, and bone density was measured by dual energy X-ray absorptiometry. Subjects also completed daily activity diaries. Subjects in the vest group reported a statistically significant decrease in bodily pain, improved physical functioning, and increased internal health locus of control. Bone density increased by 1% in the vest group and decreased by 0.6% in the controls (p = 0.12). We conclude that our exercise intervention had a positive effect on some measures of perceived health in older persons. PMID- 8518769 TI - Study protocol for the World Health Organization project to develop a Quality of Life assessment instrument (WHOQOL). AB - The World Health Organization (WHO) has undertaken a project to develop an instrument (the WHOQOL) for measuring quality of life. Quality of life is defined as an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychological state, level of independence, social relationships, and their relationship to salient features of their environment. The instrument will be developed in the framework of a collaborative project involving numerous centres in different cultural settings. In addition, it will have proven psychometric properties of validity, responsiveness and reliability and will be sensitive to the cultural setting in which it is applied, whilst maintaining comparability of scores across different cultural settings. This paper outlines the characteristics of the planned instrument and the study protocol governing work on its development. To date steps 1 through 5 have been completed and work is progressing on step 6. It is anticipated that the instrument will be available for piloting in July 1993 and a final version available for use in June 1994. PMID- 8518770 TI - The HIV quality audit marker (HIV-QAM): an outcome measure for hospitalized AIDS patients. AB - The development and validation of the HIV-Quality Audit Marker (HIV-QAM), an instrument designed to measure changes in the status of hospitalized AIDS patients due to nursing care, is reported. The HIV-QAM is designed to capture the nurse data-collector's judgment of the status of the patient based upon observations, interviews, record reviews, and listening to inter-shift report. The final version of the 10 item HIV-QAM includes three scales, Self-care (six items; Cronbach's alpha = 0.89), Ambulation (two items, alpha = 0.88), and Psychological Distress (two items, alpha = 0.84). Content validity was supported by selection of items from pre-existing scales, generation of items based on care plans for HIV/AIDS patients, and review and critique of items by a panel of nurse experts. Construct validity was supported by principal components factor analysis and multi-trait scaling analysis. Convergent and divergent concurrent validity with patient symptoms and intensity of nursing care required was demonstrated. The predictive validity of the HIV-QAM for mortality at 3 and 6 months after hospital treatment for Pneumocystis carinii pneumonia was also shown. PMID- 8518771 TI - Respiratory intensive care: a new challenge in the third millennium. PMID- 8518772 TI - When bronchoalveolar lavage and bronchial biopsies are safe in asthma. PMID- 8518773 TI - Pulsed Doppler echocardiography to assess pulmonary artery hypertension in chronic obstructive pulmonary disease. AB - Noninvasive assessment of pulmonary artery hypertension would be of great value in patients with chronic obstructive pulmonary disease (COPD). Although continuous wave Doppler echocardiographic measurement of right atrial to right ventricular pressure gradient is the most useful method of noninvasive assessment of pulmonary artery hypertension, this technique is often limited in patients with COPD. In order to evaluate the usefulness of pulsed Doppler echocardiography, for the estimation of pulmonary artery pressure in COPD patients in whom continuous wave Doppler ultrasound has failed, we compared right ventricular systolic time intervals: pre-ejection period (PEP, ms), acceleration time (AT, ms), right ventricular ejection time (RVET, ms), and AT/RVET and PEP/RVET ratios, as measured by pulmonary artery pulsed Doppler traces, in 30 COPD patients, with the time intervals of 15 age- and sex-matched healthy volunteers, using the subcostal approach. In addition, right ventricular systolic time intervals of the COPD patients were correlated with invasive catheterization data (systolic and mean pulmonary artery pressure (PAPs and PAPm). AT and AT/RVET were significantly shorter in COPD patients (AT 92 +/- 4.3 ms; AT/RVET 0.38 +/- 0.03) as compared with healthy volunteers (AT 132 +/- 4.5 ms; p < 0.001; AT/RVET 0.46 +/- 0.02; p < 0.005), whereas RVET, PEP and PEP/RVET were not significantly different in both groups. A significant correlation was demonstrated between AT and PAPs (r = -0.76; p < 0.001) and PAPm (r = -0.82; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518774 TI - Hyperinflation, trapped gas and theophylline in chronic obstructive pulmonary disease. AB - Assessment of patients with chronic airflow limitation traditionally involves the measurement of airway obstruction by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as well as hyperinflation by residual volume (RV). Patients often claim reduction of breathlessness during theophylline therapy, without change of spirometry. In severe airflow limitation there is often a difference in lung volumes measured by helium dilution and plethysmography. The latter is thought to measure the absolute amount of gas in the lungs at functional residual capacity (FRC), whereas helium dilution measures only air in rapid communication with the mouth. The difference between the two is considered to represent poorly-ventilated areas of the lung, and is termed trapped gas volume. Twenty two patients with "irreversible" airflow limitation, mean (SD) FEV1 1.15 (0.52) l, FVC 2.57 (0.88) l, were studied. Uniphyllin Continus tablets (Napp Laboratories) were given at a dose to provide a mean steady-state plasma level of 14 mg.l-1, in a placebo-controlled, double-blind, cross-over study. The measurements made were FEV1, FVC, static lung volumes, 6 min walking distance (6WD), breathlessness after exercise assessed by visual analogue scales (VAB), and arterial blood gases. No significant correlation was found between changes in VAB and changes in RV measured by the helium dilution technique (RV (He)), FEV1 or FVC, but there were good correlations with trapped gas volume (r = 0.61, p < 0.01). The plethysmographic element of the calculated trapped gas volume reflects change in the sensation of breathlessness, and is affected by treatment with theophylline. PMID- 8518775 TI - Understanding lung tissue mechanics in terms of mathematical models. AB - The mechanical properties of lung tissue are important determinants of the overall mechanical behaviour of the lung itself. Our understanding of lung tissue mechanics is embodied in various mathematical models, that relate measurements of transpulmonary pressure to lung volume and flow. The purpose of this paper is to review the most basic and important of these models. Firstly, the single compartment linear model of lung tissue is invoked to explain measurements of transpulmonary pressure and volume under quasi-static conditions, when volume excursions are modest. The exponential nonlinear extension of this model may be used to account for measurements made when volume approaches total lung capacity. Secondly, the Kelvin body as a model of the viscoelastic properties of lung tissue is considered, as a means for accounting for tissue stress adaptation and the frequency dependencies of tissue resistance and elastance. The Prandtl body is also invoked to explain tissue plastoelasticity, manifest in quasi-static hysteresis between transpulmonary pressure and volume. Finally, some more complicated and intricate extensions of these models are considered. PMID- 8518776 TI - Non-invasive mechanical ventilation in the treatment of acute respiratory failure in chronic obstructive pulmonary disease. AB - Acute respiratory failure is usually managed by means of mechanical ventilation via an endotracheal tube or tracheostomy, when conservative treatment fails. Invasive mechanical ventilation is associated with several complications. The recent development of non-invasive methods of ventilation, has led to an attempt to avoid the complications of invasive mechanical ventilation during episodes of acute respiratory failure, ensuring at the same time a similar degree of efficacy. Both intermittent negative pressure ventilation and positive pressure ventilation by face or nasal mask have recently been used for this purpose. Negative pressure ventilation by means of iron lung, cuirass or poncho-wrap ventilators, has never been used in place of endotracheal intubation, and studies of this kind of ventilation are inconclusive: as a consequence, there is, at the moment, no indication for the generalized use of negative pressure ventilation in acute respiratory failure. Intermittent positive pressure ventilation by facial or nasal masks, has recently been used in the treatment of respiratory failure in place of endotracheal intubation. The results are promising, but remain controversial. It may be attempted in selected patients with obstructive respiratory disorders, but the procedure is very time-consuming for nurses. PMID- 8518777 TI - Patient education in asthmatic adults. PMID- 8518778 TI - Spontaneous pneumothorax: medical or surgical treatment. PMID- 8518780 TI - Nasal intermittent positive pressure ventilation in neuromuscular and chest wall disease. AB - The short- and long-term physiological, functional and economic benefits of NIPPV in patients with chronic chest wall and stable neuromuscular disease have been confirmed and its advantages over non-invasive negative pressure ventilation outlined. Current research should help provide guidelines for patient selection and the most appropriate use of NIPPV in progressive neuromuscular disorders. PMID- 8518779 TI - Home mechanical ventilation in kyphoscoliosis. AB - The aim of the study was to determine whether intermittent positive pressure ventilation (IPPV), delivered either by nasal mask or by tracheostomy, is able to improve alveolar gas exchange in kyphoscoliotic patients with respiratory failure. We evaluated 17 patients, 10 females and 7 males, aged 52 +/- 12 (mean +/- SD) yrs. Eight had severe respiratory failure (arterial oxygen tension (PaO2) 53.2 +/- 9.3 mmHg (7.1 +/- 1.2 kPa); arterial carbon dioxide tension (PaCO2) 73.3 +/- 12.5 mmHg (9.7 +/- 1.6 kPa), breathing supplemental oxygen), and were put on IPPV via tracheostomy (TIPPV). The others (PaO2 54.5 +/- 5.5 mmHg (7.3 +/- 0.7 kPa); PaCO2 57.9 +/- 7 mmHg (7.7 +/- 0.9 kPa), breathing air), were put on IPPV via nasal mask (NIPPV). Home mechanical ventilation (HMV) was performed at night (7 +/- 1 h) by means of a volume-cycled pressure respirator in control mode. The frequency was adapted to the patient's spontaneous respiratory rate, and then eventually modified according to blood gases. A silicone mask was moulded onto the patient's nose. Supplemental oxygen (to maintain arterial oxygen saturation (SaO2) > 90%) was used only for tracheostomized patients, whereas NIPPV was performed with fractional inspiratory oxygen (FIO2) 21%. Arterial blood samples were obtained for all patients in steady-state condition, 8 +/- 1 h from the withdrawal, breathing air, after 1 and 6 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518781 TI - Intermittent negative pressure ventilation in patients with restrictive respiratory failure. AB - Thirty one patients in stable respiratory failure (arterial oxygen tension (PaO2) 67 +/- 20 mmHg (8.9 +/- 2.7 kPa) and arterial carbon dioxide tension (PaCO2) 59 +/- 10 mmHg 7.9 +/- 1.3 kPa)), secondary to non-obstructive ventilatory impairment, were treated by intermittent negative pressure ventilation (INPV), using a pneumowrap or poncho during the night. Daytime arterial blood gas measurements, taken before and after the ventilation, revealed a substantial improvement in PaO2, PaCO2 and maximal inspiratory pressure (Pimax). This improvement persisted during the six month follow-up of home nocturnal ventilation. The polysomnographic, recording during mechanical ventilation by poncho, in five patients, showed a general improvement in the quality and structure of sleep. All patients returned to normal arterial oxygen saturation (SaO2) values (> 90%), except for one. In three patients, the appearance of obstructive events was noted but the desaturation that they caused was, remarkably, lower than that caused by central events in baseline recording. We conclude that non-invasive treatment by INPV, in patients with neuromuscular and chest wall disease, is the method of choice as an alternative to intermittent positive pressure ventilation and to tracheostomy. PMID- 8518782 TI - Methods and prognosis of non-invasive ventilation in neuromuscular disease. AB - Ventilatory failure is the commonest terminal event in many neuromuscular disorders. Increasingly, non-invasive methods of ventilation, employing both negative and positive pressure techniques, have been used, with the aim of prolonging life and reducing morbidity. The use of non-invasive ventilation is reviewed in three main groups of neurological diseases, and the degree of success assessed. It is concluded that non-invasive methods can be effective in reducing morbidity in selected patients, especially those with more slowly progressive disorders. A reduction in mortality is suggested by comparison with historical controls. The institution of ventilatory support is a major undertaking for the medical team, patient and family, and should only be initiated after a full and frank discussion of the overall prognosis, in terms of both mortality and quality of life. The patient and principal caregivers can then make an informed decision as to the desirability of home ventilation. PMID- 8518783 TI - Respiratory prognosis in chest wall diseases. AB - In this short review focusing essentially on thoracic kyphoscoliosis, respiratory and cardiovascular abnormalities observed in different forms of this rib cage disorder are briefly described. Chest wall and pulmonary mechanics, respiratory muscles, gas exchange, pulmonary vasculature and regulation of ventilation can be markedly affected by kyphoscoliosis and a substantial growth of knowledge of these functional alterations has been allowed recently by new technological approaches. The pathophysiological process which leads to cor pulmonale and respiratory failure in some patients with kyphoscoliosis is analysed. The prognostic aspects of surgical and non-surgical management on pulmonary function are addressed. PMID- 8518784 TI - Inhaled diuretics in asthma. PMID- 8518785 TI - The needle found!!! Trinucleotide repeat expansion in the Huntington's disease gene. PMID- 8518786 TI - Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations. AB - A method for genetic diagnosis of steroid 21-hydroxylase deficiency was developed based on allele-specific PCR. With this approach, genotyping of fourteen mutations and diagnosis of homozygous gene deletions can be performed within hours from tissue sampling. One patient with salt-wasting disease had normal genotype at all positions screened. DNA sequencing revealed two novel mutations, a G to C transversion at the conserved splice donor site of intron 7 and a TGG to TAG nonsense mutation at Trp 406 in exon 9. Allele-specific PCR was established also for these mutations and used to screen for their presence in the pseudogene. However, the two novel mutations were not found in at least 34 pseudogenes. PMID- 8518787 TI - Chromosomal bar codes produced by multicolor fluorescence in situ hybridization with multiple YAC clones and whole chromosome painting probes. AB - Colored chromosome staining patterns, termed chromosomal 'bar codes' (CBCs), were obtained on human chromosomes by fluorescence in situ hybridization (FISH) with pools of Alu-PCR products from YAC clones containing human DNA inserts ranging from 100 kbp to 1 Mbp. In contrast to conventional G- or R-bands, the chromosomal position, extent, individual color and relative signal intensity of each 'bar' could be modified depending on probe selection and labeling procedures. Alu-PCR amplification products were generated from 31 YAC clones which mapped to 37 different chromosome bands. For multiple color FISH, Alu-PCR amplification products from various clones were either biotinylated or labeled with digoxigenin. Probes from up to twenty YAC clones were used simultaneously to produce CBCs on selected human chromosomes. Evaluation using a cooled CCD camera and digital image analysis confirmed the high reproducibility of the bars from one metaphase spread to another. Combinatorial FISH with mixtures of whole chromosomes paint probes was applied to paint seven chromosomes simultaneously in different colors along with a set of YAC clones which map to these chromosomes. We discuss the potential to construct analytical chromosomal bar codes adapted to particular needs of cytogenetic investigations and automated image analysis. PMID- 8518788 TI - Allele-specific MVR-PCR analysis at minisatellite D1S8. AB - Minisatellite variant repeat mapping by the polymerase chain reaction (MVR-PCR) provides a digital approach to DNA typing of great potential use both in forensic medicine and, by mapping single alleles, for exploring allelic variability and mutation processes at minisatellites. The MVR haplotypes of single alleles can be determined either from physically separated alleles or by pedigree analysis of digital diploid codes generated from both alleles simultaneously. We now show that single alleles can be rapidly mapped from total genomic DNA using allele specific PCR primers directed to polymorphic sites in the DNA flanking the minisatellite. This approach can also be used to dissect mixed DNA samples such as those often encountered in forensic DNA analysis. PMID- 8518789 TI - Apo-dystrophin-3: a 2.2kb transcript from the DMD locus encoding the dystrophin glycoprotein binding site. AB - The molecular defect in Duchenne muscular dystrophy is well established as being due to mutations at Xp21 which disrupt the normal synthesis of the 14kb dystrophin mRNA. More recently, several groups have identified a 4.8kb transcript from this locus which shares exons with the carboxy-terminal region of the dystrophin gene. In this paper we present evidence for an additional 2.2kb mRNA transcript. The 5' untranslated region and first 7 amino acids are identical to that published for the 4.8kb transcript. The position of the translational stop codon and 3' untranslated region is similar to that previously described as the truncated fetal dystrophin isoform. This 2.2kb mRNA has a similar tissue distribution to that described for the 4.8kb mRNA but unlike the other transcripts from the DMD locus, the 2.2kb mRNA is expressed in early development. The relevance of this transcript in the clinical expression of muscular dystrophy and developmental delay is discussed. PMID- 8518790 TI - Quantification of tRNA3243(Leu) point mutation of mitochondrial DNA in MELAS patients and its effects on mitochondrial transcription. AB - The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcription downstream of the ribosomal RNA (rRNA) genes, thus possibly reducing rRNA synthesis in relation to more distal transcripts. This study presents a family in which maternally transmitted diabetes and MELAS syndrome overlap, and a suggestive correlation between the amount of mutant mtDNA and clinical symptoms is observed. Mutant mtDNA was quantified in several tissues of a newborn infant and the highest amount of mutant mtDNA was found in the placenta, which is promising for the development of genetic counselling in MELAS. The consequences of the MELAS mutation were further studied in cultured clonal myoblasts. We found that the myoblasts with 93% of mutant mtDNA terminate the mitochondrial transcription, resulting in a steady-state amount of 16S rRNA 45 times as high as the more distal transcripts. However, myoblasts with a deletion of mtDNA not involving the transcription termination site had 120 times as much 16S rRNA as the distal transcripts. In both the MELAS myoblasts and in those with a deletion of mtDNA the amount of 16S rRNA increased as the mutant mtDNA increased, suggesting that the production of ribosomal RNAs is a response to the translational defect caused by the mutation. We present evidence here that the MELAS mutation causes a defect in transcription termination, thus leading to no absolute deficiency of ribosomal RNAs, but to a reduced capacity to compensate the defective translation. PMID- 8518791 TI - Isolation of cosmids and fetal brain cDNAs from the proximal long arm of human chromosome 22. AB - The proximal portion of human chromosome 22q appears to carry genes implicated in the pathogenesis of various developmental disorders, including the cat eye syndrome (CES) and the DiGeorge syndrome (DGS). A cosmid library was prepared from a radiation hybrid selected for its content in chromosome 22 fragments. A large fraction of cosmids containing human DNA were found to derive from the juxtacentromeric region of chromosome 22, as shown by fluorescence in situ hybridization (FISH) performed using individual cosmids or cosmid pools as probes. Finer mapping was obtained for individual cosmids by hybridization to a somatic cell hybrid mapping panel which splits the long arm of the chromosome into 14 bins numbered 1 to 14 from the centromere to the telomere. Of the 10 cosmids mapped, eight belonged to group 1, the other two to group 14, in agreement with FISH data. Rare endonuclease sites and fragments conserved between species were searched in single cosmids, resulting in the selection of seven cosmid fragments which were used to screen a human fetal brain cDNA library. Three cDNAs were identified, encoded from two chromosome 22 genes which appeared to be novel, as determined from partial end sequence and comparison with the database entries. Fine localization of the 30.9 cDNA indicated that the corresponding gene was located in a segment of proximal 22q overlapping with the critical DGS region. PMID- 8518792 TI - In-frame deletion of von Willebrand factor A domains in a dominant type of von Willebrand disease. AB - von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, is very heterogeneous and has been classified into several subtypes. Missense mutations have been found to be responsible for the dominant type II vWD, characterized by qualitative abnormalities affecting von Willebrand factor (vWF) function. The breakpoints of a heterozygous vWF gene deletion (31 Kb), occurring 'de novo' in a patient with a variant of type II vWD, were localized to introns 25 and 34 and sequenced. An Alu repeat in intron 25 was interrupted between the transcriptional boxes A and B. The new junction present in the abnormal von Willebrand factor mRNA was sequenced after reverse transcription of platelet RNA. The codon 1104 (Cys) is followed in frame by the mutated codon 1926 (Cys to Arg), thus removing the complete A domains, found in a wide variety of genes and characterized by independent assembly 'in vitro'. We propose that the abnormal vWF, which carries intact protein domains responsible for vWF dimer and multimer formation, makes ineffective interactions with the normal molecules in the biosynthetic process, causing the dominant type II phenotype through a novel mechanism. PMID- 8518793 TI - Molecular characterization of cytogenetic alterations associated with the Beckwith-Wiedemann syndrome (BWS) phenotype refines the localization and suggests the gene for BWS is imprinted. AB - To define the region of 11p15 involved in Beckwith-Wiedemann syndrome (BWS), we have carried out a molecular genetic analysis of six patients with features of BWS and constitutional cytogenetic abnormalities involving chromosome band 11p15. Molecular analysis confirmed the 11p origin of the duplicated material and defined the smallest region of overlap for such duplications, within which a gene involved in BWS must be located. This region encompasses the beta-globin gene complex (HBB) to 11pter. In both of our informative cases, the 11p duplication was found to be of paternal origin. Two BWS associated balanced translocations of 11p15 were studied to localize the breakpoints on 11p15. Somatic cell hybrids, Southern blotting and fluorescent in situ hybridization (FISH) showed that both breakpoints were between D11S12 and the insulin-like growth factor 2 (IGF2) gene. A non-BWS translocation breakpoint was more proximal, between HBB and calcitonin A (CALCA). Pedigree analysis showed that both BWS associated 11p15 translocations were transmitted by phenotypically normal mothers. The data are compatible with the hypothesis that the BWS gene is imprinted and that the maternally inherited BWS gene is normally suppressed whereas the paternally inherited allele is active. Thus, duplications of paternal origin would lead to increased dosage of the BWS gene. Similarly increased dosage of the BWS gene could account for the findings in maternally inherited 11p15 translocations by altering normal imprinting, so that the translocated maternal allele remains active. This study defines one or more gene loci for BWS on 11p15.5 in the genomic region from D11S12 to IGF2. PMID- 8518794 TI - No evidence of genetic heterogeneity in Brazilian facioscapulohumeral muscular dystrophy families (FSHD) with 4q markers. AB - The gene responsible for facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular condition, has been mapped to chromosome 4. Until recently, the two closest available markers were D4S139 and D4S163 but a new marker (p13E-11) which recognizes de novo rearrangements in isolated cases of FSHD characterized by shorter EcoRI fragments has been now identified. Linkage analysis in FSHD families with p13E-11 shows that usually a smaller fragment segregates with the disease gene among the affected individuals from each genealogy. In the present paper, we report the results from linkage analysis with the marker loci D4S163 and D4S139 in 6 FSHD families and with p13E-11 in these and in 6 other additional Brazilian families (total of 12). The results from such analysis do not suggest genetic heterogeneity for FSHD in our population. In 11 out of the 12 families studied with p13E-11, a shorter specific EcoRI band was found to segregate in all affected patients from each genealogy. In one family, the normal individuals had a smaller EcoRI fragment than the affected ones. The size of the EcoRI fragments detected with p13E-11 varied from 13.5 to 29 kb but was constant within each genealogy. Our results suggest that the use of the marker p13E-11 for preclinical and prenatal diagnosis should be done only in families in which it is possible to identify the fragments segregating among the affected individuals. PMID- 8518796 TI - Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F. AB - Hereditary Hemochromatosis (HFE) is one of the most common inherited disorders with an estimated frequency of homozygous patients of 0.002-0.0045. The disease is characterized by increased intestinal iron absorption and progressive iron overload. Affected subjects show clinical symptoms of parenchymal organ damage after the third-fourth decade of life and have a 200 fold increased risk of developing hepatocellular carcinoma. Early diagnosis and treatment prevent complications and may normalize life expectancy of patients. The biochemical and genetic defects leading to progressive iron accumulation are still unknown, but the HFE gene is tightly linked to HLA complex on the short arm of chromosome 6. Utilizing HLA serotypes and the study of several polymorphic markers of 6p21, a linkage analysis of the disease locus was performed in a series of Italian hemochromatosis families. The data obtained by linkage analysis and the study of a family with a double recombinant allowed us to better define the HFE gene location with respect to HLA-class I A and F loci. PMID- 8518795 TI - Five skeletal myosin heavy chain genes are organized as a multigene complex in the human genome. AB - Myosin heavy chain (MyHC) isoforms are encoded by a multigene family in vertebrates. We used genomic DNA mapping by pulse field gel electrophoresis to demonstrate that, in humans, the embryonic, fetal, fast IIB and IIX MyHC genes and a gene coding for a non-identified striated muscle MyHC fast-type isoform (NI), are contained within a 320 kb SalI genomic fragment. The locus is flanked by two CpG islands, separated by 580 kb. In order to further characterize the MyHC genes, a human genomic library constructed in yeast artificial chromosomes (YAC) was screened and five independent clones were isolated. Characterization of these YACs revealed that one of them contains at least five MyHC genes, based on partial sequencing of their conserved third coding exons. Three of these genes correspond to those encoding the embryonic, fetal and fast IIB MyHC isoforms. Moreover, in this YAC clone the embryonic and fetal genes, on the one hand, and the adult fast (IIB, IIX and NI) genes, on the other hand, are contained within two different ClaI fragments. This result suggests that the genes encoding the two developmental forms are adjacent in the human genome and that temporal regulation of the MyHC genes might be related to their organization within the locus. These data represent the first direct evidence for the existence in the human genome of a MyHC multigene locus that contains at least five genes. PMID- 8518798 TI - Correlation of a Glu/Ala substitution at position 98 with the complement C6 A/B phenotypes. PMID- 8518797 TI - X-linked liver glycogenosis: localization and isolation of a candidate gene. AB - X-linked phosphorylase kinase (PHK) deficiency causes X-linked liver glycogenosis (XLG) which is the most frequent liver glycogen storage disorder in man. Recently we assigned XLG to the Xp22 chromosomal region by linkage analysis in two families segregating XLG. In this study a further localization of XLG in Xp22 was performed by extending the number of Xp22 markers, by extension of the number of family members from the two families of our previous study and by linkage analysis in four additional XLG families. Two-point linkage analysis revealed lod scores of 4.60, 5.73, 5.28, 8.62 and 5.14 for linkage between XLG and the DNA markers pXUT23 and pSE3.2-L(DXS16), pD2(DXS43), pTS247-(DXS197) and pPA4B(DXS207), respectively, all at 0% recombination. Linkage heterogeneity was not observed in this set of families. Multipoint linkage analysis increased the lod score for linkage between XLG and Xp22 to 16.79 relative to DXS197/DXS207. The position of the XLG gene was confirmed by analysis of recombinational events locating the XLG gene between DXS85 and DXS41. The XLG gene could not be mapped more precisely in this chromosomal region of approximately 20cM because of the absence of recombinational events between the XLG gene and the Xp22 markers. As we have previously shown that the rabbit liver alpha subunit of PHK (PHKA2) hybridizes to human Xp22, we isolated a human PHKA2 cDNA from a human hepatoma lambda gt11 cDNA library. Fluorescent in situ hybridization mapped human PHKA2 to Xp22. As this physical mapping coincides with the genetic mapping of XLG by linkage analysis, PHKA2 most probably harbours the mutation(s) responsible for XLG. PMID- 8518800 TI - An 8 bp deletion in exon 51 of the COL4A5 gene of an Alport syndrome patient. PMID- 8518799 TI - Genomic organization of exons 22 to 25 of the dystrophin gene. PMID- 8518801 TI - Five novel factor IX mutations in unrelated hemophilia B families. PMID- 8518802 TI - Inactivation of phenylalanine hydroxylase by a missense mutation, R270S, in a Palestinian kinship with phenylketonuria. PMID- 8518803 TI - Dinucleotide repeat polymorphisms from DXS106 and DXS227 YACs using a two stage approach. PMID- 8518804 TI - Rapid detection of the hypertension-associated Met235-->Thr allele of the human angiotensinogen gene. PMID- 8518805 TI - Dinucleotide (CT)n (CA)n repeat polymorphism for D11S787 on chromosome 11q13.4. PMID- 8518806 TI - Dinucleotide repeat polymorphism at the DXS1111 locus. PMID- 8518807 TI - Dinucleotide repeat polymorphism at Xq26.1 (DXS1114). PMID- 8518808 TI - Dinucleotide repeat polymorphism close to IDS gene in Xq27.3-q28 (DXS1113). PMID- 8518809 TI - Dinucleotide repeat polymorphism at the DXS556 locus. PMID- 8518810 TI - Dinucleotide repeat polymorphism at D21S49 (21q22.3). PMID- 8518811 TI - Five sequence tagged sites for human chromosome band 11q23. PMID- 8518812 TI - Three dinucleotide repeat polymorphisms on chromosome 9 (D9S200, D9S201, D9S199). PMID- 8518813 TI - Dinucleotide repeat polymorphism mapping to the critical region for lissencephaly (17p13.3). PMID- 8518814 TI - Tetranucleotide repeat polymorphism at the D8S307 locus. PMID- 8518815 TI - Dinucleotide repeat polymorphism at the D21S370 locus which flanks the PRGS (GARS)-PAIS (AIRS)-PGFT (GART) gene. PMID- 8518816 TI - A new probe detecting HLA-8 gene polymorphism. PMID- 8518817 TI - Trinucleotide repeat polymorphism in the human antithrombin III (AT3) gene. PMID- 8518818 TI - A dinucleotide repeat polymorphism in the gene for the gamma subunit of the human Fc epsilon receptors (FLER16). PMID- 8518819 TI - Dinucleotide repeat polymorphism at the human erythropoietin receptor locus (EPOR) at 19p13. PMID- 8518821 TI - New human DNA polymorphisms submitted to the genome data base. PMID- 8518820 TI - A highly informative microsatellite repeat polymorphism in intron 1 of the human amyloid precursor protein (APP) gene. PMID- 8518822 TI - Comparative evaluation of materials used for internal ureteral stents. AB - The materials used in the fabrication of self-retained internal ureteral stents should provide strength, flexibility, low surface friction, radiopacity, biodurability, biocompatibility, and reasonable unit cost. Polymeric biomaterials currently used for stent construction include polyurethane, silicone, Silitek, C Flex, and Percuflex. Comparative evaluation of these materials in the context of the requirements for stent structure and function suggests advantages and disadvantages for all of them. We believe that the most important attributes for an internal ureteral stent are ease of insertion, effective restoration and maintenance of flow, resistance to migration, significant biodurability, and biocompatibility. Based on our physical testing of stents fabricated from these materials, as well as clinical and laboratory experience, we believe that C-Flex and Percuflex are the most suitable materials for stent construction. PMID- 8518823 TI - Endoluminal urethral stents: a review. AB - Although Fabian first introduced the concept of an endourethral stent in 1980, recent developments in biomedical technology and the treatment philosophy of urethral obstruction has led to a resurgence of this concept. We review the past and current literature with regard to both temporary and permanent stents. Available stents are described, clinical results summarized, and indications discussed. PMID- 8518824 TI - Percutaneous suprapubic cystostomy. AB - Suprapubic urinary diversion for the management of lesions of the bladder outlet or urethra has been facilitated by the advent of percutaneous access techniques. Prior to percutaneous endourologic techniques, an open surgical approach was necessary when the transurethral route was impassable. A variety of percutaneous suprapubic cystostomy techniques have evolved in recent years. These have been based on several different access principles and offer the urologist a number of options. Selection of an individual technique is usually a matter of preference and familiarity with a particular manufacturer's product. The list of indications for such an approach is diverse and continues to expand. PMID- 8518825 TI - External urinary diversion: pathologic circumstances and available technology. AB - A wide variety of uropathologic circumstances may necessitate intervention. All urologic interventions depend on two simple rules for success. The first is visualization (via direct-vision endoscopy or videovision endoscopy, usually in combination with external imaging via fluroscopy), as failure to visualize the area of pathology properly may compromise or doom the procedure. The second is adequate access to the urinary tract via the endoscope, which is ensured by wire, catheter, or other appropriate access device. Failure of proper access dooms interventional urologic, uroradiologic, and endourologic procedures to failure. PMID- 8518826 TI - Indwelling ureteral stents: impact of material and shape on patient comfort. AB - Indwelling ureteral stents are essential in urology today. No ideal stent has been designed. The principal sources of discomfort are a long intravesical segment, inefficient drainage, displacement, and stiffness. Discomfort may be a small price to pay for the overall benefit to the patient. PMID- 8518827 TI - Role of stents in open ureteral surgery. AB - Stents can be important adjuncts in open ureteral procedures. The authors provide guidelines to assist the surgeon in deciding whether to employ a stent. PMID- 8518828 TI - Ureteral stents and flexible ureterorenoscopy. AB - Numerous methods of dilating the intramural ureter for ureteroscopy are effective when used by experts, but none is ideal. In the authors' experience, a ureteral stent left indwelling for 1 or, better, 2 weeks usually is the safest, most reliable, and least traumatic method. PMID- 8518829 TI - The ideal ureteral stent for antegrade and retrograde endopyelotomy: what would it be like? AB - Current endopyelotomy stents are composed of polyurethane, which is an adequate biomaterial for 6 to 8 weeks of dwell time. It is easy to insert, has good internal flow, and resists encrustation. Several designs are available. External designs have the advantage of providing easy access, while the internal designs appeal to patients because no external dressing is required. On the basis of our experience, we continue to advocate the tapering external endopyelotomy stent (14F to 8F) for 6 weeks of postoperative intubation. Although urologic catheters have progressed, the perfect endopyelotomy stent has yet to be produced. PMID- 8518830 TI - Stent use with extracorporeal shock wave lithotripsy. AB - Since the advantages of using ureteral stents in conjunction with extracorporeal shock wave lithotripsy were first recognized, the growing demand for outpatient stone treatment has made stent use much more frequent. However, prophylactic stent placement must be judicious to maximize success and minimize associated morbidity. Recent controlled retrospective studies and randomized trials showed that ureteral stenting does not increase the stone-free rate or reduce the complication rate for stones less than 2 cm in size, yet in such cases, there are increased morbidities such as urinary urgency, frequency, stent migration, and encrustation. However, in patients with stones larger than 2 cm, Type C4 staghorn calculi, or stones associated with a solitary kidney, prophylactic stent placement may reduce the complication rates arising from these larger stone burdens. Finally, ureteral stenting may be helpful for stone localization or manipulation. PMID- 8518831 TI - Stents and catheters in percutaneous renal surgery. AB - Ureteral stents are commonly used either briefly or long term after percutaneous renal surgery. Most percutaneous stone procedures do not necessitate a ureteral stent, but stenting is advisable if there has been extensive trauma, perforation, or ureteropelvic junction obstruction by a large calculus. Stenting after endopyelotomy is routine, and the author has found it helpful to insert a 5F to 7F stent for 5 to 7 days preoperatively to dilate the ureter. The author reviews the available nephrostomy tubes and nephrostomy-ureteral stents, including the tamponade catheter. PMID- 8518832 TI - Tissue-bonded iontophoretic cystostomy: conceptual and experimental considerations. AB - We describe a conceptual model for drainage of the dysfunctional bladder. Experimental data from investigations involving several species of animals are presented to support the hypothesis that mature tissue-bonded alloplastic tubes drain urine effectively and are tolerant and resistant to endogenous and exogenous bacteria. We conclude that preliminary clinical trials of a tissue bonded cystostomy are warranted. We postulate that success in these trials may offer a new alternative for the management of severe vesical dysfunction. PMID- 8518833 TI - History of urethral catheters and their balloons: drainage, anchorage, dilation, and hemostasis. AB - Male urethral catheterization, as practiced in early Greece, was made possible by a sound knowledge of anatomy. It has been preserved by written tradition and advanced by the development of new materials. Balloon dilation, conceived and practiced more than 160 years ago by urologists, has undergone a similar cycle. Some useful ideas, once conceived, have been forgotten and have surfaced again, decades, sometimes centuries, later as new inventions. PMID- 8518834 TI - The pathophysiology of ureteral obstruction. AB - Ureteral obstruction can have a variety of causes intrinsic or extrinsic to the kidney. The effects of obstruction are examined from the perspectives of duration, severity, totality, and the presence of complicating factors. There is a difference in the postobstructive pathophysiology depending on whether one or both ureters were obstructed. Atrial natriuretic peptide may be important in postobstructive diuresis, and preliminary evidence suggests a role for it as protection against nephron ischemia in acute obstruction. The potential for recovery of renal function after relief of obstruction depends on the duration and degree of obstruction, the condition of the contralateral kidney, and the presence or absence of infection. Ability to acidify the urine to pH < 6.0 preoperatively may be a good predictor of the recovery potential of an obstructed kidney. Urine concentrations of lysosomal enzymes such as N-acetylglucosaminidase also may be useful for this purpose, as may measurement of creatinine clearance in urine obtained from a nephrostomy tube. PMID- 8518835 TI - Carbonyl (phenone) reductase in human liver: inter-individual variability. AB - The enzyme family carbonyl reductase, which catalyses the reduction of xenobiotic as well as endogenous ketones and aldehydes, has not been very well studied in terms of its biological functions and structural aspects. The aim of the present study was to check for the occurrence of inter-individual variability of carbonyl reductase activity in human liver. In vitro metabolism of p-nitroacetophenone (PNAP, a prototype substrate) indicated the presence of a high- and low-affinity enzyme site. The reductase activity of 17 kidney donor livers was screened at two concentrations (0.05 and 0.5 mM PNAP, below and above Km). The rates of reductase activity at 0.05 mM suggested a normal distribution. In contrast, at 0.5 mM the rates indicated a non-normal distribution, i.e. bi- or tri-modality. As an index of variability of enzyme affinity, ratios of velocities at 0.5 to 0.05 mM PNAP were calculated in order to check their frequency distributions. Three out of 17 kidney donor livers showed an atypical ratio. In these three cases, the high ratio was due to the low activity of the high affinity form of carbonyl reductase. Autopsy livers are a more readily available tissue source and about half the activity of the kidney donor livers was found in 43 autopsy livers indicating that they are a useful source of human tissue for studies of carbonyl reductase. PMID- 8518836 TI - Catechol O-methyltransferase pharmacogenetics: photoaffinity labelling and western blot analysis of human liver samples. AB - The level of catechol O-methyltransferase (COMT) activity and COMT thermal stability in human tissue are controlled by a common genetic polymorphism. We studied individual hepatic biopsy samples shown previously to have phenotypically high, low or intermediate COMT activities and thermal stabilities to test the hypothesis that the molecular mass (M(r)) and/or isoelectric point (pI) of the enzyme might differ in tissue from subjects with different presumed genotypes for the COMT genetic polymorphism. COMT was partially purified from each hepatic tissue sample by sequential ion exchange and gel filtration chromatography, and photoaffinity labelling was performed with [3H-methyl]-S-adenosyl-L-methionine ([3H-methyl]-Ado-Met), the methyl donor for the COMT enzymatic reaction. Two dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis (2-D SDS PAGE) analysis of individual samples consistently showed the presence of three [3H-methyl]-Ado-Met photoaffinity labelled proteins with pI values of 5.4, 5.5 and 5.7, all three of which had M(r) values of approximately 27.1 kDa. The same pattern was observed in all samples irrespective of COMT phenotype. Western blot analysis of 2-D SDS-PAGE gels performed with rabbit polyclonal antibodies to partially purified human kidney COMT showed a pattern similar to that found during photoaffinity labelling. Once again, the same pattern was found in all samples irrespective of COMT phenotype. Therefore, neither photoaffinity labelling nor Western blot analysis revealed differences in either M(r) or pI of cytoplasmic COMT in hepatic tissue from subjects selected on the basis of different phenotypic expression of the COMT genetic polymorphism. PMID- 8518837 TI - Hepatic microsomal tolbutamide hydroxylation in Japanese: in vitro evidence for rapid and slow metabolizers. AB - Microsomal hydroxylation of tolbutamide in Japanese livers was studied in vitro to ascertain the enzyme catalysing this reaction. Rates of tolbutamide hydroxylation differed individually 33-fold and 42-fold at 0.1 mM and 2.4 mM tolbutamide concentrations, respectively, and were segregated into two groups, rapid and slow metabolizers. An antibody raised against P450 human-2 (a form of CYP2C9) strongly inhibited the hydroxylation in livers of rapid metabolizers but only weakly inhibited in the slow metabolizer. Kinetic experiments further demonstrated a clear distinction in tolbutamide hydroxylation between two groups; the mean of apparent Km values for tolbutamide was 0.25 mM (n = 3) in the rapid group and 2.58 mM (n = 2) in the slow, respectively. These data suggest that different enzymes are involved in the hydroxylation in both metabolizer groups. Furthermore, CYP2C9 produced by cDNA expression in yeasts, catalysed tolbutamide hydroxylation at rates similar to the rapid metabolizer group at both the 0.1 mM and 2.4 mM concentrations. The apparent Km value of the expressed protein for tolbutamide, 0.26 mM, was similar to that determined for the rapid group of microsomal samples. Clear correlations were observed between the rate of microsomal tolbutamide hydroxylation at 0.1 mM and CYP2C9 protein content or the rate of S-mephenytoin 4'-hydroxylation in human liver. These results indicate that considerable portions of microsomal tolbutamide hydroxylation are catalysed by CYP2C9 or the closely related form in the rapid metabolizers. PMID- 8518838 TI - Tolbutamide hydroxylation in humans: lack of bimodality in 106 healthy subjects. AB - The tolbutamide hydroxylation capacity was studied in 106 healthy unrelated volunteers from the Australian population. Following a 500 mg oral dose of tolbutamide, the ratio of metabolites (hydroxytolbutamide plus carboxytolbutamide) to unchanged tolbutamide excreted in urine from 6 to 12 h post-dose (urinary metabolic ratio, MR) was determined. Metabolic ratio values did not appear bimodally distributed, even following various transformations of the data (i.e. Log10, inverse, Log10 inverse). A poor metabolizer (PM) subject from a previous clinical study, however, could be distinguished (MR value 159) from the above subjects (MR value range 324-3033), particularly from the histogram plot of inverse tolbutamide metabolic ratio. The poor metabolizer's parents had metabolic ratio values (526 and 478) that were at the lower end of the range of metabolic ratios obtained from the population study, and may indicate that they both have a heterozygous genotype and that a recessive form of inheritance is most likely. As the hydroxylations of tolbutamide and phenytoin are closely linked, the incidence of slow tolbutamide metabolizers is likely to be similar to that for phenytoin (about 1:500) and this is consistent with the failure to detect a single poor tolbutamide metabolizer in our random sample of 106 individuals. PMID- 8518839 TI - [The mechanisms of the formation of the plateau phase of the ureteral action potential]. AB - The duration of the AP plateau was shown to be controlled by the Na+ and Li+ ions in the solution incubating the smooth muscle of the ureter. Addition of ouabain to the sodium solution or replacement of the Na+ ions by the Li+ those shorted the plateau duration. The generation of the AP plateau seems to be due to participation of the Na(+)-Ca++ exchange mechanism. PMID- 8518840 TI - [The effect of an antioxidant on the neuronal impulse activity of the prefrontal and inferotemporal cortices during visual recognition in monkeys]. AB - The antioxidant oxymetacil improved cognitive characteristics and activated neuronal activity in the monkey prefrontal area in the process of delayed visual differentiation of different colour stimuli. It also considerably increased the mutual correlation coefficients between neuronal responses in prefrontal and inferotemporal cortex. The data obtained suggest a contribution of neuronal structures of these areas into the improvement of the cognitive characteristics. PMID- 8518841 TI - [The morphofunctional heterogeneity of the m. cremaster capillary bed in Wistar rats]. AB - Intravital microscopy revealed that 65% of all the m. cremaster's capillary bed were perfused at rest. The capillary functional reserve may play an important part in the topographical heterogeneity of the perfusion. The heterogeneity is a passive mechanism in an increasing number of perfused capillaries, i.e. the "capillary recruitment". PMID- 8518842 TI - [Oxygen tension in the brain of rats with acute immersion hypothermia]. PMID- 8518843 TI - [Neurotrophic control of the smooth muscles in the bladder]. PMID- 8518844 TI - [The characteristics of the cardiopulmonary baroreceptor reflex in man]. PMID- 8518845 TI - [N. E. Vvedenskii--teacher]. PMID- 8518846 TI - [The behavioral and neurohormonal manifestations of emotional stress states in monkeys]. AB - Under the effect of intense stressful stimuli baboons developed a depressive state. The disintegration of individual and social behaviour correlates with changes in functional activity of steroid-producing glands and the dynamics of the blood endorphin concentration, thus suggesting involvement of the opioid peptide system and the hypophyseal-gonadal complex in mechanisms of stress induced depressive states. PMID- 8518847 TI - [Changes in the functions and biorhythms of the normal rabbit ECoG]. AB - The rabbit ECoG is characterised by alternating active and inhibitory signs. This suggests the necessity to take into consideration individual features and initial states of the rabbit CNS and the dynamics of their changes when studying the effects of various stimuli. PMID- 8518848 TI - [The localization of corticosteroid receptors in the dopaminergic structures of the canine brain]. AB - Dopaminergic structures of the dog brain were found to be able to specifically bind corticosteroid hormones. The data obtained suggest localisation of corticosteroid receptors on the terminals of dopaminergic receptors. PMID- 8518849 TI - [Horizontal optokinetic nystagmus in th pigeon during static tilts in the sagittal plane]. AB - The mode of symmetrical position-related otolith influences modified the parameters of optokinetic nystagmus in pigeons. The symmetry of temporonasal nasotemporal responses was due to increase in the NT-stimulation efficiency. The parameters of optokinetic nystagmus seems to depend on the direction of the otolith membrane shifts. PMID- 8518850 TI - [The reactions of the capillary bed of the skeletal muscles to normobaric hyperoxia and a perfluoro-organic blood substitute]. AB - The capillary density of the m. cremaster decreased while the RBC velocity and tube hematocrit remained constant during oxygen respiration in rats. The blood substitute induced opposite changes. The data suggest that the RBC velocity decrease depended on the blood rheological properties due to addition of submicron particles of the blood substitute and not to its oxygen capacity. PMID- 8518851 TI - [The functional activity of the portal vein as a reflection of the metabolic changes in experimental chronic kidney failure]. AB - The vein contractility was shown not to depend on the nitrogen-excreting function of kidneys in rats with subtotal nephrectomy. The role of veins' increasing functional activity in the organism's compensatory-adaptive response after a decrease in renal functioning parenchymal mass, is discussed. PMID- 8518852 TI - [The dynamic activity of the posterior roots of the thoracic spinal cord during ionic-osmotic stimulation of the liver]. AB - Spontaneous rate of discharges of the T6-8 segments and their responses to ionic and osmotic stimuli resembled those of the individual receptor units of the liver. The data suggest that the hepatic intravasal, vasal-interstitial and interstitial volumoreceptors and "water" osmoreceptors have their afferent link in the spinal pathway. PMID- 8518853 TI - [The administration of corticoliberin into the caudate nucleus activates the sympathetic-adrenal medullary and hypophyseal-adrenal cortical systems by different mechanisms]. AB - The activation was revealed, through a considerable increase of levels of adrenaline, noradrenaline and cortisol. Corticotropin-releasing factor seems to act upon the sympatho-adrenal system (SAS) via dopaminergic mediation. The mechanisms of triggering of the SAS and pituitary-adrenocortical system by the corticotropin-releasing factor seem to be different and due to involvement of different extrahypothalamic structures in the regulating contours. PMID- 8518854 TI - Struvite calculi. PMID- 8518855 TI - Influence of ionic strength on crystal adsorption and inhibitory activity of macromolecules. AB - We investigated the influence of ionic strength on both the binding ability of macromolecules onto calcium oxalate crystals and the inhibitory activity of macromolecules related to calcium oxalate crystal growth and aggregation in vitro. The amount of heparin sodium salt adsorbed onto calcium oxalate crystals was studied in both a seed and a non-seed crystal system at various ionic strengths with the aid of radiolabelled heparin. In both adsorption models, adsorption of heparin was greater in the buffered solutions of lower ionic strength, and significantly so in the range of physiological ionic strength. The inhibitory activity of heparin in the non-seed crystal system, which was determined using a Coulter Multisizer, increased as the adsorbed dose increased. The naturally existing urinary macromolecules showed a similar change in their inhibitory activity on calcium oxalate crystal growth and/or aggregation in accordance with changes in ionic strength. These results indicate that macromolecular inhibitory activity seems to be enhanced in urine of lower ionic strength as a result of an increased adsorption of macromolecules on the surface of calcium oxalate crystals. PMID- 8518856 TI - Increased fractional excretion of sulphate in stone formers. AB - This study was performed to determine urinary sulphate excretion in patients with renal stone disease. Stone formers showed a significantly higher fractional excretion of sulphate than control subjects; 80% of stone formers had fractional excretions > 0.26. No significant relationship was established between increased urinary sulphate excretion and any identifiable metabolic disorder, or the recurrence rate of stone episodes. The increase in fractional excretion of sulphate appears to be a more prevalent tubular defect among stone formers than has hitherto been reported. PMID- 8518857 TI - Serum and urinary zinc levels in urolithiasis. AB - Zinc has an important place amongst inhibitors of crystallisation and crystal growth. These views are supported by in vivo and in vitro studies which suggest that the urinary zinc level is a significant factor in urolithiasis. Some recent studies have given contradictory results. Blood serum and urinary zinc levels were measured in 30 normal healthy controls and 42 stone forming patients (renal, ureteric and vesical). Statistically significant levels were found in all groups, varying according to the number of calculi. Increased urinary zinc levels and decreased serum zinc levels appear to be secondary to the process of stone formation. The role of zinc as an inhibitor of urolithiasis is questionable. PMID- 8518858 TI - The role of the radionuclide renal study in the management of renal colic. AB - If renal colic is suspected in the patient presenting with acute flank or lower abdominal pain it must be established whether or not the affected kidney is obstructed and whether there is functional impairment that may require urological intervention. The radionuclide renal study developed in this hospital and used routinely for over 10 years can reveal obstruction when the results of commonly used tests are negative. It also provides information on renal function, morphology and blood flow. It is a cost-effective, safe and reliable procedure for the initial investigation of patients presenting with suspected renal colic. PMID- 8518859 TI - Surgical correction of bilharzial ureteric stricture by Boari flap technique. AB - Extensive ureteric strictures due to bilharziasis can be managed satisfactorily by reimplantation of the ureters using a Boari flap technique. A series of 150 patients with extensive ureteric strictures underwent ureteric reimplantation using this technique. Contrary to the conventional belief that patients with bilharziasis have a contracted bladder, our patients maintained a good capacity and sufficient supple tissue was available to replace even very extensive ureteric strictures. PMID- 8518860 TI - The value of videourodynamics in the investigation of neurologically normal children who wet. AB - Videourodynamic studies were performed on 57 wet children, 35 of whom were assessed retrospectively and 22 prospectively. Thirty-two studies (56%) were abnormal; detrusor instability or reduced compliance was found in 26, increased bladder sensitivity in 3, detrusor sphincter dyssynergia in 2 and sphincter weakness incontinence in 1. A detailed micturition history sheet and the results of routine preliminary investigations (mid-stream urine and ultrasonography) were used in an attempt to predict the outcome of urodynamics. Since only 5 of the 25 normal studies and 18 of the 32 abnormal studies were correctly predicted, it was concluded that accurate prediction was not possible. Urodynamic investigations are therefore required to identify the underlying cause of wetting and to guide appropriate treatment. PMID- 8518862 TI - Improved results using a modification of the Young-Dees-Leadbetter bladder neck repair. AB - Forty-seven patients with primary total incontinence underwent bladder neck reconstruction (BNR) between 1978 and 1988. This included 31 patients with exstrophy/epispadias, 14 with myelomeningocele and 2 with caecoureteroceles. The patients were divided into 5 groups based on the type of BNR: Group 1--standard Young-Dees-Leadbetter (YDL) BNR; Group 2--YDL+Silastic sheath; Group 3--modified YDL; Group 4--Kropp BNR; Group 5--other BNRs. Group 1 included 18 patients with a 45% primary continence failure rate, a 44% reoperation rate and only a fair ability to void spontaneously after BNR. There were 11 patients in Group 3 with a 9% primary continence failure rate, a 27% reoperation rate and excellent post operative emptying. None of the 3 patients in Group 4 was incontinent post operatively, but they all required reoperation and had poor post-operative emptying. We feel that the modified YDL BNR provides better overall voiding and continence with less morbidity than the other bladder neck/urethral reconstructive procedures. PMID- 8518861 TI - Experimental model of bladder outflow tract obstruction in the guinea-pig. AB - Bladder outflow tract obstruction was produced in immature female guinea-pigs. Obstruction caused an increase in voiding pressure and bladder weight and a decrease in bladder compliance. No change occurred in the sensitivity of obstructed detrusor strips to exogenous agonists, but the force of contraction and response to electrical stimulation of the intrinsic nerves were less than in the strips from controls. The response of strips from sham-operated animals to exogenous agonists and to electrical stimulation was greater than that from obstructed animals. The effects of length and tension could not account for the in vitro responses from obstructed animals. Histology after obstruction showed muscle hypertrophy, connective tissue infiltration and decrease in nerve density. Many of the changes resembled those seen in the obstructed human bladder. PMID- 8518863 TI - Relative indications for orthotopic lower urinary tract reconstruction, continent urinary diversion and conduit urinary diversion. AB - Continent urinary diversion has become increasingly popular in the last few years and there are now several situations in which ileal conduit diversion, continent diversion and orthotopic reconstruction of the lower urinary tract are equally valid options. This review was intended to determine specific indications for each. Of 513 patients treated for severe lower urinary tract problems in the last 10 years, 399 underwent orthotopic reconstruction, 68 underwent continent diversion and 46 had an ileal conduit. Problems occurred 2 to 3 times more commonly in the continent diversion group than in either of the other groups. Given a free choice, most patients would choose an orthotopic reconstruction and this should probably be regarded as the gold standard. Continent diversion is specifically indicated in male patients who require a total cystourethrectomy for bladder cancer, in severe post-radiotherapy problems, and in patients with neuropathic bladder dysfunction in whom, for various reasons, self catheterisation is impossible. Ileal conduit diversion remains the simplest and safest technique in high-risk patients and does not preclude a subsequent continent diversion or orthotopic reconstruction. PMID- 8518864 TI - Magnetic resonance imaging in the staging of bladder cancer. AB - Magnetic resonance imaging (MRI) scans were performed on 55 bladder cancer patients on whom clinicopathological staging was available from transurethral resection and cystectomy specimens. The overall accuracy of MRI scanning in this group was 84%, although true concordance rates are debatable without open surgical correlation. In the subgroup of 25 patients who had accurate open surgical correlation (from cystectomy, laparotomy or post mortem) the concordance rate was 76% with MRI. Errors occurred mainly in the T3 group of tumours, with 2 being overstaged and 2 being understaged out of a total of 12 in the open surgical correlation group (66% accuracy). Difficulties were also encountered in staging tumours at the bladder base, with an error rate of 22% (2 of 9) for T4 tumours in this area. With regard to lymph node staging there was a 100% (5 of 5) specificity in defining pathologically involved nodes but there was a false negative rate of 15% (3 of 19). Although it has many advantages over CT scanning, MRI produces a significant error rate in terms of over- and under-staging invasive tumours. There are difficulties associated with detecting minimal involvement of adjacent organs and lymph nodes as well as determining the exact depth of muscle penetration. Improvements may come in the future with the use of contrast enhancement agents such as gadolinium as well as more advanced machines. PMID- 8518865 TI - Aspirin and post-prostatectomy haemorrhage. AB - Haemorrhage occasionally occurs following transurethral prostatectomy, and it may be severe. In this study a relationship between severe haemorrhage and ingestion of aspirin is documented. This is explicable in terms of the anti-aggregatory affects of aspirin on platelets. There may also be a problem with other types of non-steroidal anti-inflammatory agents. Surgery should be undertaken with caution on patients taking these common medications. PMID- 8518866 TI - Treatment preferences of urologists in Great Britain and Ireland in the management of prostate cancer. AB - A questionnaire was sent to all full-time British and Irish urologists (n = 278) on the management of prostate cancer and was answered by 229 (82%). The questions included 3 specific clinical situations, namely the management of incidental disease, the timing of treatment for metastatic disease and the mode of hormonal manipulation used for advanced disease. It was found that 79% of urologists preferred a deferred treatment policy for incidental disease in the over-75 age group. Radical prostatectomy was advocated by 10% of those questioned for patients in the under-60 age group. Radiotherapy was the mainstay of treatment for incidental disease in the poorer prognosis groups of incidental disease, namely younger patients with more aggressive tumours. Most urologists treated patients with asymptomatic metastatic disease at the time of diagnosis, with 18% entering patients into the Medical Research Council trial comparing immediate with deferred therapy. Orchiectomy was advocated by 57% of urologists as their first-line treatment for patients where hormonal manipulation was indicated. Consequently orchiectomy should remain the "gold standard" in comparative phase III trials in advanced prostate cancer. PMID- 8518867 TI - LHRH analogues as primary treatment for urinary retention in patients with prostatic carcinoma. AB - Thirty-one patients with retention of urine and carcinoma of the prostate were treated with LHRH analogues as primary therapy rather than prostatectomy; 21 patients voided without the need for surgical intervention. Patients presenting in acute retention of urine voided more readily than those presenting in chronic retention, with only 20% requiring surgery. This approach to treatment is safe, efficacious and cost effective. PMID- 8518868 TI - Effect of parenteral testosterone therapy on penile development in boys with hypospadias. AB - Forty boys with hypospadias received 2 mg/kg testosterone esters intramuscularly 5 and 2 weeks before surgical correction of the hypospadias. The effects on penile development were determined 3 and 5 weeks after the first injection and 3 and 12 months post-operatively. A significant effect on penile development was shown. This effect disappeared during the first year following treatment. There was no effect on bone maturation, children's height and the ultimate testosterone level. All adverse effects disappeared after cessation of therapy. Androgen receptor deficiency as a possible cause of hypospadias is not supported by our observations. PMID- 8518869 TI - Dicentric Y chromosome in azoospermic males. AB - Two azoospermic, infertile men with a pseudodicentric Y chromosome are reported. The small isodicentric Y chromosomes were composed of duplicated short arm and proximal long arm Y, as proven by fluorescence in situ hybridisation using a Y centromere-specific DNA probe, pDP97, and a short arm probe pY-80. Both lacked germinal cells in the gonads. It was assumed that the azoospermia was caused by deletion or disruption of the azoospermic factor gene located at distal Yq11. Patient 2 measured 147 cm (-4.1 SD) in height and so it was assumed that he had also lost the "statural determinants" gene. PMID- 8518870 TI - Tumours of the spermatic cord and paratesticular tissue. A clinicopathological study. AB - A total of 85 patients with paratesticular tumours were diagnosed over a period of 36 years at this hospital; 66 patients (78%) had benign tumours, usually either an adenomatoid tumour or a lipoma. Of the remaining 19 malignant cases, 10 were primary neoplasms and 9 were metastases. A rare mucin-secreting epididymal adenocarcinoma was the only primary malignant epithelial tumour, the others being of mesenchymal origin. In 4/9 metastatic cases the initial presentation of a paratesticular swelling led to the discovery of the occult primary neoplasm following histological examination. Clinical features of a painful or painless mass, with or without an accompanying hydrocele, do not help to distinguish a benign from a malignant lesion. The prognosis of malignant tumours of mesenchymal origin depends mainly on the histological grade. Surgical resection remains the mainstay of treatment and adjuvant therapy significantly improves the chances of survival only in young patients with paratesticular rhabdomyosarcomas. Older patients with high grade tumours usually succumb to their disease despite chemotherapy and/or radiotherapy. PMID- 8518871 TI - Does vasectomy cause testicular cancer? AB - Between 1975 and 1990, 330 men developed testicular tumours in Northern Ireland. Their names were cross matched with a sample of 2904 men who had undergone vasectomy between 1970 and 1985. The expected numbers of tumours in vasectomised patients was 2, while the actual number was 1. Our experience does not indicate that vasectomy causes testicular cancer. PMID- 8518872 TI - Emphysematous pyelonephritis: drainage or nephrectomy? AB - Four cases of emphysematous pyelonephritis are reported and the pathogenesis, surgical implications and preferred mode of management are discussed. We have not found percutaneous drainage to be useful, but feel there is an important place for surgical drainage alone because of the potential for renal recovery and the risks of emergency nephrectomy. PMID- 8518873 TI - Seminoma of the testis following testis-sparing excision of teratoma. PMID- 8518874 TI - Anaphylaxis following urethral catheterisation. PMID- 8518875 TI - Recurrent urinary infection secondary to urethral duplication. PMID- 8518876 TI - Self-castration as treatment for alopecia. PMID- 8518877 TI - Posterior urethral valves in twins with mirror image abnormalities. PMID- 8518878 TI - Propranolol in the control of haemorrhage from varices around a urostomy. PMID- 8518879 TI - The Klippel-Trenaunay syndrome associated with renal artery aneurysm. PMID- 8518880 TI - Transitional cell carcinoma in an ileal conduit. PMID- 8518881 TI - A new technique for removal of the urolume prostate stent. PMID- 8518882 TI - Perineally-based scrotal skin flap to cover the inguino-scrotal defect resulting from radical removal of scrotal mesothelioma. PMID- 8518883 TI - Subcuticular suture in circumcision. PMID- 8518884 TI - Incomplete urethral duplication treated by endoscopic scissors. PMID- 8518885 TI - Role of topical mitomycin C in upper urinary tract transitional cell carcinoma. PMID- 8518886 TI - A simple ureteric function test: intraoperative and post-operative uses in pyelopasty. PMID- 8518887 TI - Endoscopic sphincterotomy in acute gallstone pancreatitis. PMID- 8518888 TI - Laser angioplasty. PMID- 8518889 TI - Laparoscopic cholecystectomy. AB - After laparoscopic cholecystectomy, the patient can expect a hospital stay of < 2 days and a return to work within 2 weeks. The associated operative mortality rate is low at < 0.2 per cent. The increased incidence of bile duct injury with the laparoscopic technique compared with open cholecystectomy is a cause for concern but such injuries should decrease with proper training in laparoscopic surgery. The use of operative cholangiography (whether routine, selective or never) is controversial but there is no evidence that routine cholangiography will prevent major bile duct injury. PMID- 8518890 TI - Radiological investigation in acute diverticulitis. AB - Optimal management of acute sigmoid diverticulitis depends on evaluation of the severity of the inflammatory process, in which radiological investigation is a useful but probably underutilized adjunct to clinical assessment. Plain abdominal radiography shows abnormalities in 30-50 per cent of patients but these tend to be non-specific and more accurate information is obtainable from a contrast enema. Although the quality of images produced by a water-soluble contrast agent is inferior to that with barium, the former is less hazardous in the presence of perforation and provides sufficient information to permit rational management decisions to be made. Ultrasonography and computed tomography (CT) are particularly useful in visualizing abscesses. They may be helpful in following the progression or resolution of suppuration and in guiding percutaneous aspiration when appropriate. Despite early reports to the contrary, CT is no more specific than a contrast enema in the diagnosis of acute diverticulitis. Radionuclide scans have little role in the routine assessment of acute diverticulitis and magnetic resonance imaging has not been adequately evaluated. Water-soluble contrast enema is safe, widely available and probably the most useful early supplementary investigation. PMID- 8518891 TI - Modern management of pancreatic pseudocysts. AB - Pseudocysts may develop as a complication of acute pancreatitis, chronic pancreatitis or pancreatic trauma. As new methods of imaging provide fuller information on their incidence and natural history, important differences are emerging between the pseudocysts of acute and chronic pancreatitis. Traditional surgical approaches to the management of pseudocyst are now being challenged by endoscopic techniques and interventional radiology. In the light of these developments the options available are reviewed and strategies for the modern management of pancreatic pseudocysts are suggested. PMID- 8518892 TI - High prevalence of unsuspected abdominal aortic aneurysm in patients with confirmed symptomatic peripheral or cerebral arterial disease. AB - A group of 561 consecutive patients with proven symptomatic peripheral or cerebral arterial disease attending a vascular clinic was screened for abdominal aortic aneurysm (AAA) using B-mode ultrasonography. An aneurysm was present in 40 of 358 men (11.2 per cent) and 13 of 203 women (6.4 per cent), a total prevalence of 9.4 per cent. Thirty-three aneurysms were 3-4 cm in diameter. The prevalence of AAA was similar in patients referred with lower-limb and with cerebral ischaemia. Physical examination for AAA was performed in 200 patients before ultrasonography. The sensitivity of physical examination in the detection of aneurysm was 43 per cent (57 per cent for AAA > or = 4 cm in diameter, 29 per cent for AAA < 4 cm in diameter). Physical examination was an inadequate method of screening. Initial follow-up showed a mean aneurysm expansion rate of 0.20 cm/year. Patients with arterial disease have a high risk of AAA; routine ultrasonographic screening should be considered. PMID- 8518893 TI - Comparison of long-term survival after successful repair of ruptured and non ruptured abdominal aortic aneurysm. AB - Long-term survival was assessed after the repair of non-ruptured (n = 311) and ruptured (n = 227) abdominal aortic aneurysm. Follow-up was 94.2 per cent complete, and the overall survival rate at 8 years was 43.6 per cent. There was no significant difference in 8-year survival rates between patients with non ruptured (45.2 per cent) and ruptured (40.5 per cent) aneurysms. The survival curves were also compared with that for an age- and sex-matched population derived from Scottish Home and Health Department data. PMID- 8518894 TI - Mesothelial seeding of knitted Dacron. AB - Bilateral superficial femoral artery replacement using knitted Dacron was performed in 38 dogs. One side was seeded with omental mesothelium and the other acted as an unseeded control. 111In-labelled platelet accumulation on grafts was measured at 5 days and 2 months and the thrombogenicity index of seeded and unseeded grafts calculated. Patency was monitored for 2 months, at which time grafts were removed and luminal thrombus, ultrastructural cell cover and prostacyclin release were measured. Cell seeding did not influence the mean(s.e.m.) thrombogenicity index of 0.95(0.25) and 0.88(0.24) at 5 days in control and seeded grafts respectively; nor was there any difference between the groups at 2 months. Occlusion occurred in six control and four seeded grafts. Seeding did not significantly improve the percentage thrombus-free area or luminal cell cover. Neither did it enhance mean(s.e.m.) luminal 6-keto prostaglandin F1 alpha release of 2.58(0.80) pg cm-2 in controls and 2.63(0.78) pg cm-2 in seeded grafts. Further studies demonstrated that only a mean(s.e.m.) of 4.4(1.9) per cent of the seeded inoculum was present on grafts 48 h after implantation, providing too few cells to achieve confluent cover. Mesothelial cell seeding might be useful in promoting a healed graft surface but critical levels of seeding density must be achieved before the technique can be properly evaluated. PMID- 8518895 TI - Peripheral arterial thrombolysis: intermediate-term results. AB - To determine the intermediate-term results of intra-arterial thrombolysis, 127 consecutive patients receiving 129 courses of treatment were reviewed at a median follow-up of 3 years. At initial review, 30 days after treatment, thrombolysis was successful in 63 cases (49 per cent). Of these patients, 16 were lost to follow-up: 15 died without further vascular symptoms and one moved from the area. Some 35 patients were alive and asymptomatic, of whom 33 had either angiographic or clinical evidence of continued arterial patency. Symptomatic reocclusion occurred in 12 cases; a further two patients remained asymptomatic and reocclusion was detected at follow-up. Two of the 12 symptomatic patients required amputation. Estimated patency rates were 80 per cent at 1 year, 72 per cent at 2 years and 70 per cent at 3 years. The intermediate-term results in the 66 cases in which lysis was unsuccessful were worse, only 16 patients (24 per cent) surviving to follow-up with the treated limb intact. It is concluded that, if thrombolysis is successful at 30 days, the intermediate-term results are good. PMID- 8518896 TI - Tissue and urokinase plasminogen activators in the environs of venous and ischaemic leg ulcers. AB - Urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) were assayed in biopsies from the base, edge and adjacent skin of ischaemic and venous ulcers using a functional bioimmunoassay and a standard immunoassay. Two series of 14 biopsies were examined: from seven venous and seven ischaemic ulcers in the first series, eight venous and six ischaemic in the second. It was found that tPA was detected in only four samples of ulcer edge using the bioimmunoassay and in no sample by the standard immunoassay. By contrast, uPA was detected in all but one ulcer edge biopsy and at a significantly lower median concentration in the adjacent skin (16.9 units/g) than the ulcer edge (26.1 units/g) or base (32.3 units/g) (both P < 0.01). Levels of uPA were greater in the edge and base of venous compared with ischaemic ulcers. The predominant plasminogen activator in chronic leg ulcers is uPA; this activator may play an important role in wound healing. PMID- 8518897 TI - Long-term circulatory access via a peripheral implantable port. AB - The use of a novel indwelling central venous catheter system is described which combines the safety of peripheral venous catheter placement with a novel electromagnetic locator device for guidance of the catheter tip into the correct position. This locator system obviates the need for radiological screening or chest radiography for checking catheter placement. Fifty-one patients were studied prospectively and all were successfully cannulated. An infection rate of 0.29 per 1000 catheter-days was seen with a mean system life of 220 (range 15 510) days. The new port has a lower infection rate than other commonly used systems and eliminates complications such as pneumothorax and puncture of major arteries. PMID- 8518898 TI - Results of a prospective randomized trial of the Angelchik prosthesis and of a consecutive series of 119 patients. AB - The results of a randomized multicentre trial comparing the Angelchik prosthesis with floppy Nissen fundoplication for gastro-oesophageal reflux were assessed 4-6 years after surgery. Of the original 52 patients 48 were traced. A good or excellent result (Visick grade 1 or 2) was obtained in 21 of 25 after insertion of the Angelchik prosthesis compared with 18 of 23 after fundoplication. Poor results were due to recurrent heartburn after fundoplication and to dysphagia after prosthesis insertion. In a separate consecutive series of 119 patients receiving Angelchik prostheses, results were good or excellent in 101 (85 per cent) and poor in 18 (15 per cent). Control of reflux with a correctly positioned prosthesis was good. Troublesome dysphagia (Visick grade 3 or 4) was experienced in eight of the 119 patients. There was no mortality and no incidence of splenectomy or gas-bloat syndrome. PMID- 8518899 TI - Prognostic significance of cell culture in carcinoma of the oesophagus. AB - The prognostic significance of the potential of cells to grow in tissue culture was studied in 50 patients with oesophageal cancer. The ability of cell lines to grow from resected oesophageal specimens was determined; from 50 patients, 21 cell lines were established (42 per cent). The patients were divided into two groups on this basis: group 1, from whom cancer cells could be grown as continuous cell lines and group 2, from whom cell lines could not be established. The cumulative survival rate of patients in group 1 was significantly lower than that of those in group 2 (P < 0.05). There was also a significantly higher incidence of lymph node metastases in group 1 (P < 0.05). These results suggest that the potential of cancer cells for growth is a useful long-term prognostic indicator for patients with oesophageal carcinoma. PMID- 8518900 TI - Prospective randomized study of one- or two-layer anastomosis following oesophageal resection and cervical oesophagogastrostomy. AB - In a prospective randomized study, one- and two-layer anastomoses were compared following subtotal oesophagectomy and gastric substitution with cervical oesophagogastric anastomosis. After 54 one- and 53 two-layer procedures the rates of anastomotic leakage were the same (19 per cent). After a mean follow-up of 44 weeks, 13 of 51 patients (25 per cent) undergoing one-layer anastomosis and 28 of 50 (56 per cent) having the two-layer procedure complained of cervical dysphagia and required dilatation. The anastomotic strictures were fibrotic in 11 of 51 patients (22 per cent) undergoing one-layer anastomosis and in 24 of 50 (48 per cent) receiving the two-layer operation. Strictures were malignant in two and four patients (4 and 8 per cent) respectively. The lower incidence of fibrotic stricture following one-layer anastomosis was significant (P < 0.01), but not that of malignant stricture. With comparable leakage rates, one-layer anastomosis is superior to the two-layer procedure because of the lower incidence of fibrotic stricture. PMID- 8518901 TI - Subtotal splenectomy with a microwave coagulator. PMID- 8518902 TI - Spontaneous rupture of the spleen secondary to metastatic carcinoma. PMID- 8518903 TI - Rectus repair for midline ventral abdominal wall hernia. AB - Recurrence-free repair of midline ventral abdominal wall hernia continues to elude surgeons, despite the abundance of described techniques. Based on the observation that spontaneous herniation through the rectus abdominis muscles is unknown, a new technique of repair was devised. The rectus muscles and their sheaths on either side of the hernial defect are directly brought together to obliterate the hernia, the intervening linea alba and intact hernia sac being 'keeled' into the abdominal cavity. Using this technique, 85 consecutive midline abdominal hernias were repaired over an 11-year period. Follow-up was from 18 months to 12 years; there was one recurrence. The rectus repair is recommended as an effective method of dealing with ventral midline abdominal wall hernia. PMID- 8518904 TI - Incidence of haemorrhoids and anorectal varices in children with portal hypertension. AB - A prospective study of 60 children with portal hypertension showed a significant incidence of haemorrhoids (33 per cent), anorectal varices (35 per cent) and external anal varices (15 per cent). Four children (7 per cent) complained of anorectal symptoms. A comparison of extrahepatic with intrahepatic disease showed that the former was associated with a higher incidence of both haemorrhoids and anorectal varices (57 versus 26 per cent and 64 versus 26 per cent respectively). The occurrence and severity of haemorrhoids was related to the number of previous oesophageal sclerotherapy sessions (P = 0.001). Problems relating to anorectal pathology were unusual, but treatment with haemorrhoidal sclerotherapy or banding was satisfactory for the symptomatic patients. PMID- 8518905 TI - Intraoperative testing of the valtrac biofragmentable anastomotic ring. PMID- 8518906 TI - Perineural invasion of carcinoma of the pancreas and biliary tract. AB - Carcinoma of the pancreatobiliary system often produces perineural invasion extending to extrabiliary and extrapancreatic sites. A surgical technique has been developed to manage this invasion and has been used since 1974. Serial sections were prepared from 90 resected specimens and examined for perineural involvement of intramural and extramural biliary plexuses as well as the pancreatic nerve plexus. Perineural invasion was seen in 34 of 40 patients with carcinoma of the common bile duct, in ten of 14 with cancer of the gallbladder and in four of 15 with carcinoma of the papilla of Vater. Invasion extended to the extramural biliary or pancreatic nerve plexuses in 24 of 40 patients with carcinoma of the bile duct. Involvement of the intrapancreatic nerves was seen in all 21 patients with carcinoma of the pancreatic head and that of the pancreatic nerve plexus in 17 of 21. Perineural invasion was often found at the most progressive margin of the tumour. The survival rate of patients with perineural invasion was low compared with that of those without such invasion, although survival of patients with perineural invasion tended to be longer after extensive resection. The perineural space should be regarded as an important route for the spread of pancreatic and biliary carcinoma. PMID- 8518907 TI - Cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile duct dilatation. AB - The aim of this study was to delineate clinical features and prognosis of cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile duct dilatation, and to determine methods for managing the disease. A retrospective study of seven patients is presented. A further 27 cases from the Japanese literature were reviewed retrospectively with regard to method of treatment and prognosis. In 11 of 18 patients in whom staging was known the tumour was stage V, representing advanced disease. In seven of 34 cases curative operation was performed; only two patients survived for > 3 years. This poor outcome was due largely to delayed diagnosis of cancer of the gallbladder. Prophylactic cholecystectomy is recommended in patients with this anomalous junction without bile duct dilatation or a malignant lesion in the gallbladder, because of the high incidence of cancer of the biliary tract. PMID- 8518908 TI - Temporary loop ileostomy for restorative proctocolectomy. AB - The aim of a defunctioning ileostomy after restorative proctocolectomy is to mitigate the consequences of pelvic sepsis, should it occur. However, there are complications related to the ileostomy itself. Of 310 patients (174 male and 136 female; mean age 33.2 years) who underwent restorative proctocolectomy between 1976 and 1990, 296 had a covering ileostomy and 14 did not. The stoma has been closed in 263 (88.9 per cent) at a median interval from formation of 12.0 weeks. Ileostomy-related complications before closure occurred in 17 patients (5.7 per cent). Laparotomy for obstruction due to the ileostomy was required in seven patients (2.4 per cent). Retraction requiring revision occurred in three patients (1.0 per cent), an abscess behind the stoma in one (0.3 per cent) and miscellaneous appliance problems in seven (2.4 per cent). Following closure, 59 patients overall (22.4 per cent) developed an ileostomy-related complication. There were 30 cases of small bowel obstruction, treated conservatively in 19 (7.2 per cent) and by laparotomy in 11 (4.2 per cent). Peritonitis requiring laparotomy occurred in three patients (1.1 per cent) and two (0.8 per cent) developed an enterocutaneous fistula. There were 14 (5.3 per cent) wound infections and 16 (6.1 per cent) other miscellaneous problems. Significant complications associated with a temporary ileostomy were less frequent in this series than in some other reports. Obstruction was the most common complication and fistula was rare. PMID- 8518909 TI - Possible role of the autonomic nervous system in sphincter impairment after restorative proctocolectomy. AB - Peroperative manometry was performed in 12 patients operated on with endoanal proctectomy and a hand-sewn pouch-anal anastomosis and in 12 in whom proctectomy was performed entirely from above, with the ileal pouch stapled to the top of the anal canal. Results from both groups showed that division of the superior rectal artery reduced the median (95 per cent confidence interval (c.i.)) resting anal pressure from 77.5 (69.9-83.3) mmHg to 64.5 (55.2-70.0) mmHg (P < 0.01). Complete rectal mobilization to the pelvic floor decreased resting pressure by an additional 22 per cent, to a median of 50.0 (95 per cent c.i. 40.1-53.5) mmHg (P < 0.01). After completion of anastomosis, irrespective of the operative technique used, a further decline in median pressure to 35.0 (95 per cent c.i. 26.0-47.7) mmHg could be demonstrated (P < 0.05). This study indicates that anal sphincter pressure is reduced to a similar extent after hand-sewn and stapled anastomoses. Injury to the autonomic nervous supply to the anal sphincter mechanism might be the major cause for this reduction. PMID- 8518910 TI - Oestrogen and progesterone receptors in colorectal cancer and human colonic cancer cell lines. AB - Receptors for oestrogen (ER) and progesterone (PR) were assayed in tissue from 17 patients with colorectal cancer and five colonic cancer cell lines using enzyme immunoassays. ERs and PRs were detected in 15 and 17 cancers respectively, although the levels detected were low: median (range) ER 1.3 (0-11.3) and PR 3.9 (0.3-10.2) fmol per mg protein. These values were not significantly different from median (range) levels of ER (1.1 (0.6-3.0) fmol/mg) and PR (1.9 (0.5-3.2) fmol/mg) detected in normal mucosa. There were significant positive correlations between the levels of ER and PR for cancer tissue (tau = 0.56, P < 0.005; r(log transform) = 0.68, P < 0.003; n = 17) but not for mucosa, and between levels of ER in cancer tissue and mucosa (tau = 0.55, P < 0.05; r(log transform) = 0.70, P < 0.025; n = 10) but not between the corresponding PR values. In maintenance media, which contained phenol red and unstripped fetal calf serum, the median (range) concentration of ER was 1.9 (1.2-10.4) fmol/mg and that for PR 24.3 (9.1 63.2) fmol/mg in the five cell lines studied (HT-29, LS174T, SW620, LoVo, COLO 320DM). The addition of oestradiol (10 nmol/l) to phenol red-free medium containing 5 per cent dextran-coated charcoal-treated fetal calf serum had little effect on the concentration of ERs or PRs in SW620, LoVo and COLO 320DM cells after 7 days' culture. It is concluded that ERs and PRs are expressed in malignant and normal colonic mucosa. ERs appear to be a feature of the colonic mucosa rather than the malignant process, but in carcinoma may regulate synthesis of PRs, suggesting a degree of oestrogen responsiveness. PMID- 8518911 TI - 'Car-crusher colon'. PMID- 8518912 TI - Timing of surgery for breast cancer in relation to the menstrual cycle and survival of premenopausal women. PMID- 8518913 TI - Prevalence of abdominal aortic aneurysm in the offspring of patients dying from aneurysm rupture. PMID- 8518914 TI - Mechanical properties of the aneurysmal aorta. PMID- 8518915 TI - Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. PMID- 8518916 TI - Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. PMID- 8518917 TI - Small bowel transit time in patients with intra-abdominal adhesions. PMID- 8518918 TI - Immunocytochemical demonstration of nerve growth factor (NGF) receptor in the pineal gland: effect of NGF on pinealocyte neurite formation. AB - Nerve growth factor receptor immunoreactivity (NGFRI) in the pineal gland was examined both light and electron microscopically using the monoclonal antibody 192IgG. NGFRI was located on sympathetic fibers and on perivascular cells resembling macrophage/microglia. A pineal gland dispersed cell culture model confirmed the presence of NGFRI in cells that exhibited processes of varying lengths and were distributed among pinealocytes and other flat cells. Pinealocytes in dispersed cell culture were identified immunocytochemically by their expression of S-antigen, their round shape and small size and their tendency to extend neurites in the direction of the flat cells in culture. The length of pinealocyte neurites showed a significant increase when cultured in the presence of NGF (25 ng/ml), suggesting that trophic factors, mediated by these macrophage/microglial cells, are important to the morphogenesis of these neuroendocrine cells. Neurotrophic activation of these neuroendocrine macrophage/microglia may have neuro-immunomodulatory implications leading to expression of proteins encoded by the major histocompatibility complex. PMID- 8518919 TI - Central cardiovascular effects of AVP and AVP analogs with V1, V2 and 'V3' agonistic or antagonistic properties in conscious dog. AB - To determine central cardiovascular effects of arginine vasopressin (AVP) in the dog, and the nature of the receptors involved, blood pressure (BP) and heart rate (HR) responses were monitored in 18 conscious dogs subjected to third ventricle (i.c.v.) infusions of either AVP or AVP analogs with agonistic or antagonistic properties towards V1, V2 and putative 'V3' receptors. Significant blood pressure (BP) increases were elicited by i.c.v. infusions of: (i) AVP at a rate of 0.01, 1 and 100 ng/min; (ii) the selective V1 agonist (F180, Ferring) at a rate of 1 and 100 ng/min, and (iii) the selective V1 antagonist, dEt2 Tyr(Me)DAVP at a rate of 100 ng and 400 ng/min. Pretreatment with another selective V1 antagonist (MeCAAVP) increased baseline BP and prevented AVP induced BP increase. Blood pressure was not altered by i.c.v. infusions of the selective V2 agonist dVDAVP, the selective V2 antagonist d(CH2)5[D-Ile2,Abu4]AVP, the putative 'V3' agonist vasopressin-(4-8) (Akzo Organon), mediating behavioral actions of AVP and by artificial CSF. Heart rate was significantly accelerated by AVP infused at a rate of 100 ng/min. The results reveal high sensitivity of the conscious dog to central pressor action of AVP and indicate that this effect is mediated by V1 like receptors. It is suggested that the pressor effect of the V1 antagonist may result from its partial agonistic properties towards central V1 receptors, however, it can not be excluded that endogenous AVP released under baseline conditions may exert tonic hypotensive effect mediated by a different population of V1 receptors, this effect being abolished by V1 antagonist. The results do not support involvement of V2 or 'V3' receptors in central cardiovascular actions of AVP. PMID- 8518920 TI - Sex differences in striatal dopamine: in vivo microdialysis and behavioral studies. AB - Experiments were conducted to examine sex differences in striatal dopamine function using in vivo microdialysis in freely moving rats. We report here a sex difference in basal extracellular striatal dopamine determined by quantitative microdialysis (the no net flux method) when castrated and ovariectomized rats were compared. There was no sex difference in dopamine uptake into synaptosomes. This indicates that the sex difference in extracellular dopamine is most likely due to sex differences in dopamine release, synthesis, and/or metabolism. Within 30 min after a single injection (s.c.) of either estradiol benzoate (2.0 micrograms/100 g) or 17 beta-estradiol (1.5 micrograms/100 g) the amphetamine stimulated release of dopamine was enhanced in the striatum of ovariectomized rats, but there was no effect in castrated male rats. The enhanced amphetamine induced striatal dopamine release in ovariectomized rats was associated with an enhanced frequency of stereotyped head and limb movements and an increased peak in extra 1/4 turns. There were also sex differences in stereotyped behavior and extra 1/4 turns whether or not animals received estrogen treatment. Thus, there are sex differences in striatal extracellular dopamine and in the effect of estrogen on the striatal dopamine neurochemical and behavioral responses to amphetamine. PMID- 8518921 TI - Early changes of macrophage-like immunoreactivity in the rat inferior olive after intraperitoneal 3-acetylpyridine injection. AB - Early changes of macrophage-like immunoreactivity were observed in the inferior olive after intraperitoneal injection of 3-acetylpyridine (3AP) using seven monoclonal antibodies recognizing macrophage subpopulations (OX-42, OX-6, ED-1, RM-1, TRPM-1, TRPM-2, and TRPM-3). Both resting and activated forms of microglia were stained with OX-42 and TRPM-2. Some of activated microglia reacted to OX-6 and/or ED-1. Neither resting nor activated microglia reacted to any of RM-1, TRPM 1, and TRPM-3. Four h after 3AP injection, the processes of OX-42-positive microglia had increased in number and became thicker than resting microglia. Between 24 h and the 7th day after 3AP injection (day 7), OX-42-positive microglia gradually increased in number. At 24 h after 3AP injection, round cells appeared that stained with all seven antibodies. These disappeared by day 3. Double staining indicated that OX-42-positive activated microglia on day 7 were divided into subpopulations by their immunoreactivity to ED-1. We suggest that the round cells derived from blood monocytes and entered the brain only transiently while OX-42-positive activated microglia originated from parenchymal resting microglia and continued to increase in number after the disappearance of the round cells. PMID- 8518922 TI - The dentate gyrus is sexually dimorphic in prepubescent rats: testosterone plays a significant role. AB - In a morphological examination of the hippocampal formation of pre-pubescent rats, a testosterone-related sexual dimorphism was observed. The dentate gyrus granule cell layer was greater (8-9%) in width and length and laterally asymmetrical in males and in testosterone-treated females. This dimorphism was previously observed in adult rats. These data demonstrate that the dimorphism exists prior to puberty and is therefore not dependent on hormone changes associated with this event. In addition, a correlation between the size of this cell layer and performance on a spatial task were observed. PMID- 8518923 TI - Norepinephrine injections in diagonal band of Broca selectively reduced the activity of vasopressin supraoptic neurons in the rat. AB - In the rat, transient drug-induced elevations of arterial blood pressure, which are sufficient to activate peripheral baroreceptors, produce a brief and selective cessation in the spontaneous activity of vasopressin-secreting cells in the hypothalamic supraoptic nucleus. This response appears to require the noradrenergic innervation of the diagonal band of Broca. The present study evaluated whether injections of norepinephrine into the diagonal band of Broca affect the spontaneous activity of supraoptic vasopressin-secreting neurons. Extracellular recordings were obtained from antidromically identified supraoptic neurons in pentobarbital anesthetized rats using a transpharyngeal approach. Injections of 200 nl of 10 microM norepinephrine into the diagonal band of Broca region arrested the spontaneous activity of 80% (12/15) of vasopressin-secreting neurons but only 7% (1/14) of oxytocin secreting-neurons demonstrated a comparable decrease in excitability. Vehicle injections did not influence the activity of any of the neurons tested. These results are consistent with the hypothesis that the baroreceptor-sensitivity of vasopressin neurons is mediated by a noradrenergic mechanism in the diagonal band of Broca. PMID- 8518924 TI - Energetics and glucose metabolism in hippocampal slices during depolarization: 31P and 13C NMR studies. AB - Alterations in the energy state and glucose metabolism of hippocampal slices exposed to high extracellular K+ ([K+]o) were monitored using 31P and 13C NMR spectroscopy. Slices were perfused (37 degrees C) continuously within the NMR spectrometer and tissue viability and metabolic activity were maintained for at least 18 h. 31P spectra showed that upon exposure to 40 mM [K+]o, there was a rapid compromise in tissue energetics where, by 15 min of exposure, the ratio of phosphocreatine and of nucleoside triphosphates to inorganic phosphate (extra- and intracellular) decreased 30-50% relative to pre-exposure values. This was accompanied by a pH decrease of approximately 0.3 units in both the intra and extracellular environments. A lower but stable energy state was reached at approximately 15 min of exposure and full recovery was observed by 30 min following the removal of high [K+]o. Utilizing 13C NMR in the presence of [1 13C]glucose, an immediate and dramatic acceleration in tissue glycolysis was observed when slices were exposed to 40 mM [K+]o: the rates of both [1 13C]glucose consumption and [3-13C] acetate synthesis increased by approximately 20 fold. By 60 min following the removal of high-[K+]o, pre-exposure rates of tissue glycolysis were restored. The results indicated that the rapid and dramatic induction of energy production via glycolysis probably accounts for the ability of hippocampal slices to maintain viability and recuperate from brief but intense depolarizing conditions which are reminiscent of seizure states in vivo. PMID- 8518925 TI - The activity of an analogue of MPF (beta-endorphin 28-31) in a rat model of Parkinson's disease. AB - A single intrastriatal injection of a slow release formulation of a metabolically stable MPF analogue was given to rats with lesioned right nigrostriatal pathways. After 6 weeks the turning behaviour of the rats in response to D-amphetamine began to decline, and after 12 weeks the reduction was marked and consistent. The implication of our results in the use of intracerebral grafts in parkinsonian patients is discussed. PMID- 8518926 TI - Fluorescent estimation on the effect of Ca2+ antagonists on the oxidative metabolism in dissociated mammalian brain neurons. AB - Effect of organic Ca2+ antagonists on the oxidative metabolism or the formation of reactive oxygen species was estimated on dissociated mammalian neurons using a flow cytometer and 2',7'-dichlorofluorescin which is oxidized to be fluorescent by cellular oxidants. Of the organic Ca2+ antagonists used, flunarizine and nifedipine decreased the intensity of fluorescence at 1 microM or more while it was not the case for verapamil and diltiazem, suggesting one of the favourable actions of flunarizine and nifedipine on ischemic brain damage. PMID- 8518927 TI - Sensitivity to N-methyl-D-aspartic acid-induced convulsions is genetically associated with resistance to ethanol withdrawal seizures. AB - Mice genetically selected to be resistant (withdrawal-seizure resistant, WSR) or prone (withdrawal-seizure prone, WSP) to handling-induced convulsions during ethanol withdrawal were tested for sensitivity to convulsions induced by timed intravenous (i.v.) infusion of N-methyl-D-aspartic acid (NMDA). WSR mice displayed convulsions at infused doses of NMDA that averaged 20% lower than WSP mice. This result was present in both genetically independent replicates of the WSR and WSP mice and provides strong evidence for an involvement of the NMDA system in the difference in withdrawal seizures present in these lines. PMID- 8518928 TI - Noradrenergic mechanisms for the anticonvulsant effects of desipramine and yohimbine in genetically epilepsy-prone rats: studies with microdialysis. AB - A large body of evidence suggests that the seizure-prone state of genetically epilepsy-prone rats (GEPRs) results, in part, from deficits in central nervous system noradrenergic function. In order to link the synaptic concentration of norepinephrine (NE) to seizure behavior, we evaluated the effects of both desipramine and yohimbine on convulsions and on extracellular NE and serotonin (5 HT) concentrations in the thalamus of severe seizure GEPRs (GEPR-9s). Under anesthesia, guide cannulae were stereotaxically placed over thalami. After recovery from surgery, dialysis probes were inserted and the animals were placed individually into a plexiglass chamber where they were allowed to move about freely. Artificial CSF was perfused and samples were collected for analysis on HPLC with electrochemical detection. Either desipramine (10 and 20 mg/kg) or yohimbine (10 mg/kg) was administered i.p. after a stable baseline of NE or 5-HT was established. Significant increases in the extracellular NE concentration were seen after injection of both drugs. Temporal linkage exists between the maximum NE increase and the maximum decrease in audiogenic response score (ARS) for these two agents. No significant increases in the extracellular 5-HT concentration occurred after administration of either desipramine or yohimbine at a dose of 10 mg/kg. We conclude that these two drugs are effective anticonvulsants in GEPRs at least partially because they enhance noradrenergic transmission. PMID- 8518929 TI - ATP release from dorsal spinal cord synaptosomes: characterization and neuronal origin. AB - The present study determined the Ca(2+)-dependence of the release of adenosine 5' triphosphate (ATP) from dorsal spinal cord synaptosomes evoked by depolarization with K+ and capsaicin, and the effect of intrathecal capsaicin pretreatment, dorsal rhizotomy and intrathecal pretreatment with 6-hydroxydopamine on such release. Release of ATP evoked by K+ was Ca(2+)-dependent, while that evoked by capsaicin was Ca(2+)-independent. Capsaicin pretreatment (60 micrograms, 7 days), which lesions small diameter afferents, did not alter release of ATP evoked by either K+ or capsaicin. Dorsal rhizotomy, which lesions all afferents, produced a significant reduction in the amount of ATP released from the rhizotomized side compared to the intact side. Pretreatment with 6-hydroxydopamine (100 micrograms, 7 days) to destroy adrenergic nerve terminals, markedly reduced spinal cord noradrenaline levels, but did not alter the K(+)-evoked release of ATP. These results suggest that some K(+)-evoked release of ATP could originate from large but not small diameter afferent nerve terminals in the spinal cord. ATP does not appear to originate from small diameter afferents as, although ATP is released by in vitro exposure to capsaicin, such release occurs only at high concentrations, release is Ca(2+)-independent and it is unaltered by pretreatment with capsaicin. The bulk of the ATP released from the spinal cord does not originate from descending noradrenergic nerve terminals. PMID- 8518930 TI - Brain alpha-tocopherol levels are not altered following ischemia/reperfusion induced cerebral injury in rats and gerbils. AB - alpha-Tocopherol (alpha-TC) is considered an important endogenous brain antioxidant. The utility of brain alpha-TC levels as an index of in vivo lipid peroxidation has recently been suggested. Therefore, we explored the significance of alpha-TC levels in brains to ischemic insults associated with global or focal cerebral ischemia. Four ischemic models were used and alpha-TC was measured by HPLC. Brain alpha-TC levels in gerbils exposed to 20 min bilateral carotid artery occlusion (CAO) and 60 min reperfusion was 10.8 +/- 2.1 micrograms/g (x +/- S.D., n = 6) vs. 10.8 +/- 1.8 micrograms/g (n = 6) in sham controls. In gerbils subjected to 3 h unilateral CAO and 2 h RP, a procedure marked by neurological abnormalities, brain alpha-TC levels of ischemic and non-ischemic hemispheres were essentially the same (10.7 +/- 1.6 vs. 10.1 +/- 1.4 micrograms/g, n = 4). In rats subjected to 80 min unilateral middle cerebral artery occlusion followed by 60 min reperfusion, or 6 h occlusion without reperfusion, the brain alpha-TC levels in ipsilateral ischemic and contralateral non-ischemic cortex were not different (12.1 +/- 1.2 vs. 11.9 +/- 2.6 micrograms/g or 12.2 +/- 1.6 vs. 13.4 +/ 1.2 micrograms/g, n = 4-8). Our results demonstrated that brain alpha-TC levels can not be used as index of ischemia/reperfusion related lipid peroxidation or tissue injury. PMID- 8518931 TI - Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. AB - The present study was undertaken to determine the role of injured fibers in the development of neuropathic pain using our earlier established rat model. Our model was produced by placing tight ligatures to the L5 or both the L5 and L6 spinal nerves on one side in the rat. These rats showed long-lasting behavioral signs of mechanical allodynia and heat hyperalgesia. Using the uniqueness of our model, 3 specific questions are being asked concerning the initiation and maintenance of behavioral signs for neuropathic pain. The results of behavioral tests performed after various surgical manipulations suggest that: (1) peripheral nerve injury itself is the critical factor for the development of behavioral signs of neuropathic pain; (2) signs of neuropathic pain appear only when injury occurs at a part of the peripheral nerve distal to the dorsal root ganglion; and (3) signals (either electrical or chemical) entering the spinal cord from the injured fibers or the dorsal root ganglion cells play a critical role for both initiation and maintenance of the neuropathic pain state. PMID- 8518932 TI - Alterations and recovery of rat brain gangliosides and glycosidases following long-term exposure to alcohol and rehabilitation during development. AB - The present study examines effects of continuous exposure to alcohol during gestation, lactation and postweaning periods and rehabilitation on gangliosides and their catabolizing enzymes in whole brain (WB), cerebrum (C), cerebellum (CB) and brain stem (BS) of 63-day-old rats. Continuous exposure to alcohol was found to cause significant deficits in the body and brain weights. On the other hand, the concentration of total ganglioside in whole brain, cerebrum, cerebellum and brain stem showed an increase following exposure to alcohol. In agreement with the increased ganglioside concentration the activities of sialidase, beta galactosidase, beta-glucosidase and beta-hexosaminidase, which are likely to be involved in the catabolism of gangliosides, showed reductions due to alcohol. Alcohol was also found to alter the proportions of individual gangliosides and the changes were found to be region-specific. However; the alcohol-induced alterations were reversed, at least to some extent, upon abstinence from alcohol. Body weights of control (CT), alcoholic (AC) and rehabilitated (AR) rats were 164 +/- 2, 107 +/- 7 and 139 +/- 3 (mean +/- S.E.M.), respectively. Decrease in tissue weight was significant in whole brain, cerebrum and brain stem but not in cerebellum. In AR rats significant deficits in tissue weights persisted in cerebrum and almost a complete recovery was observed in brain stem. On the other hand, the increase in the concentration of gangliosides in WB, C, CB and BS of AC rats amounted to 23, 19, 19 and 53% of controls, respectively. The corresponding values for the AR rats were 12, 14, 3 and 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518933 TI - Towards an improved survival of rat brain neurons in culture by cerebrospinal fluid of patients with senile dementia of Alzheimer's type. AB - Neuronal cell survival was investigated in rat brain cortical cultures in the presence of increasing concentrations of human brain extracts or cerebrospinal fluid (CSF) from control and Senile Dementia of Alzheimer's type (SDAT) patients. Using hippocampal brain extracts, converted 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) was compared to the content of the neuronal marker MAP2 in foetal rat brain neuronal cultures in order to test converted MTT as a quantitative parameter for neuronal cell survival. A significant correlation was found between both parameters. SDAT frontal cortex brain extracts induced a two four-fold increase in neuronal cell survival at 25 to 125 micrograms protein extract, whereas control brain extracts induced at similar protein concentrations a decline in neuronal cell survival. The enhanced survival yielded by SDAT brain extracts was fully abolished in the presence of control brain extract. Control CSF concentration-dependently increased neuronal cell survival in postnatal rat brain neuronal cultures independent of the difference in the protein content of CSF samples and age of the patients. SDAT CSF also concentration-dependently enhanced neuronal cell survival, however, the effect was more pronounced compared to control CSF. These observations are in favour of the hypothesis that there might be a higher neurotrophic activity in SDAT brain tissue. PMID- 8518934 TI - Effects of central and peripheral administration of arginine vasotocin and related neuropeptides on blood pressure and heart rate in the conscious trout. AB - The cardiovascular activity of neurohypophyseal peptides has been investigated in conscious trout bearing an intracerebroventricular guide cannula and a permanent intraarterial catheter. Changes in diastolic pressure, systolic pressure and heart rate were monitored during the 25-min period following intracerebroventricular or intraarterial administration of arginine vasotocin and related neuropeptides, including arginine vasopressin, oxytocin, hydrin-2, mesotocin, isotocin and conopressin-S. Intracerebroventricular injection of increasing doses of arginine vasotocin (0.62-5 pmol) induced a dose-dependent increase of diastolic and systolic pressures. The onset of the response occurred within 3-5 min after intracerebroventricular administration of arginine vasotocin and the maximal increase was reached at 10-15 min. Central administration of vasopressin and oxytocin induced a significant rise in diastolic and systolic pressures at a dose of 5 pmol while hydrin-2 only caused a significant elevation of blood pressure at a dose of 50 pmol. Central administration of mesotocin, isotocin and conopressin-S (5-500 pmol each) had no significant effect on blood pressure. No changes in heart rate occurred after intracerebroventricular injection of any of the seven neuropeptides tested. Intraarterial injection of arginine vasotocin (50 pmol) induced a significant rise in blood pressure and bradycardia. Peripheral injection of the other neuropeptides did not cause any modification of the cardiovascular activity, whatever the doses administered (5 500 pmol). The V1A receptor antagonist [d(CH2)5, Tyr(OMe)2]arginine vasopressin had no intrinsic effect on blood pressure and heart rate when injected centrally (50 pmol) or in the peripheral circulation (200 pmol). At the same doses, [d(CH2)5, Tyr(OMe)2]arginine vasopressin reduced by 50 and 66%, respectively, the increase in blood pressure evoked by intracerebroventricular (5 pmol) or intraarterial (50 pmol) injections of arginine vasotocin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518935 TI - Potential bioactivated neurotoxicants, N-methylated beta-carbolinium ions, are present in human brain. AB - Potential bioactivated neurotoxicants, 2-N-methyl-beta-carbolinium and 2,9-N,N' dimethyl-beta-carbolinium ions, as well as N-methylation activities which form these charged species, were analyzed for the first time in the parietal association cortex and the substantia nigra of human brain using GC/MS and HPLC. The brains were taken during forensic autopsies from corpses without obvious degeneration of substantia nigra. In the cortex, 2-methyl-norharmanium ion (2 MeNH) and 2,9-dimethyl-norharmanium ion (2,9-Me2NH) were detected in almost all samples. 2-Methyl-harmanium ions (2-MeHA) and 2,9-dimethyl-harmanium ions (2,9 Me2HA) were detectable in only two samples. In substantia nigra samples pooled from 3 or 4 brains for analysis, 2-MeNH and 2,9-Me2NH levels were higher than those in the cortex, whereas 2-MeHA and 2,9-Me2HA were below detection limits. Their precursors, norharman (NH) and harman (HA), were also measured using HPLC/fluorescence detection. In both regions, NH and HA were present in almost all samples; levels of NH and HA were also significantly higher in the nigra than in the cortex. Using 9-methyl-NH and 2-MeNH as substrates, in vitro N-methylation of the 2[beta] and 9[indole] nitrogens toward beta-carbolines was measured both in the cortex and in the nigra. 2[beta]-N-Methylation activity was significantly higher than 9[indole]-N-methylation activity in both regions. Recent studies show that beta-carbolinium ions resemble the synthetic parkinsonian toxicant, MPP+, with respect to structure and neurotoxic activity. Such 'bioactivated' carbolinium ions could be endogenous causative factors in Parkinson's disease. PMID- 8518936 TI - Developmental effect of testosterone on estrogen sensitivity of the rat preoptic neurons with axons to the ventral tegmental area. AB - The neonatal effect of testosterone on neuronal sensitivity to estrogen was examined in the medial preoptic area of the rat when adult. Electrical stimulation of the ventral tegmental area induced antidromic action potentials in 683 neurons in 106 urethane-anesthetized animals which consisted of 38 males castrated on the day of birth (day 1), 30 females androgenized by testosterone injection on day 5, and 38 normal females. All females were used after ovariectomy when adult. Histological localization of the antidromically activated neurons was similar in all the animal groups. The latency jump in 40% of the potentials indicated that activated preoptic axons terminate in the stimulation site. The latency for activation was in the range 1.6-43.7 ms and the threshold was as low as 60 microA. The absolute refractory period did not exceed 1700 microseconds. Estrogen increased the threshold among 278 cells in the normal females and 181 cells in the neonatally castrated males. Preoptic neurons in the androgenized females (n = 224) differ from those in others in that their threshold, regardless of estrogen treatment, was at the ceiling values seen in the other groups in the presence of estrogen. Estrogen also prolonged the absolute refractory period in the females but not in the androgenized females. The reduced excitability and the lack of estrogen sensitivity may be responsible for the insensitivity of the androgenized females to feminine actions of estrogen, that may presumably underlie a sex difference in certain behavioral functions. PMID- 8518937 TI - The effects of capsaicin, bradykinin, PGE2 and cicaprost on the discharge of articular sensory receptors in vitro. AB - The responses of articular sensory receptors to capsaicin, bradykinin, PGE2, and the selective IP-receptor agonist cicaprost were studied in a rat isolated hindlimb in vitro preparation. Long-term maintenance of normal sensory receptor function was achieved in vitro under conditions of combined superfusion and slow perfusion. Response characteristics to mechanical or chemical stimuli on articular sensory receptors identified in this study did not differ to those reported in vivo. This preparation lacks complex effects mediated via spinal or central reflex mechanisms and allows greater control over the physiological environment of the receptors being studied. These results support the conclusion that the effects of capsaicin, bradykinin and the prostanoids are mediated by distinct pharmacological receptors associated with articular sensory nerve endings. The potent potentiating effects of cicaprost on bradykinin-induced excitation suggests that these actions are mediated via IP-receptors. PMID- 8518938 TI - The role of dopamine in the maintenance and breakdown of D1/D2 synergism. AB - The neurochemical factors involved in the maintenance and breakdown of dopamine D1/D2 receptor synergism were investigated by giving rats various pharmacological treatments that diminish the ability of dopamine to interact with its D1 and/or D2 receptors. Following these treatments, rats were observed for the expression of stereotyped motor behavior in response to independent stimulation of D1 or D2 receptors. Independent D2-mediated responses were observed: (a) 2 h after the last of three daily reserpine (1 mg/kg) injections, (b) 48 h after bilateral 6 hydroxydopamine (6-OHDA) lesions of the mesostriatal pathways, (c) 24 h after a concentrated 48-h regimen (one injection/6 h) of eticlopride (0.5 mg/kg) or eticlopride+SCH 23390 (0.5 mg each), and (d) 2 h after a concentrated 48-h regimen (one injection/6 h) of alpha-methyl-p-tyrosine (alpha MPT; 100 mg/kg), but not after control treatments or a concentrated regimen of SCH 23390 alone. By contrast, independent D1-mediated responses were observed only after three daily reserpine injections or 48 h after bilateral 6-OHDA lesions. Independent D1 mediated stereotypy was not observed under control conditions or following a concentrated 48-h regimen of (a) SCH 23390 or eticlopride (0.5 mg/kg each) alone or in combination, (b) a high dose of SCH 23390 (1.0 mg/kg), (c) alpha MPT (100 mg/kg), or (d) alpha MPT (100 mg/kg)+SCH 23390 (1.0 mg/kg). Reserpine, bilateral 6-OHDA, and alpha MPT treatments produced striatal dopamine depletions of 96%, 92%, and 71%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518939 TI - Immunoelectron microscopic demonstration of oxytocin and vasopressin in pituicytes and in nerve terminals forming synaptoid contacts with pituicytes in the rat neural lobe. AB - A pre-embedding immunoelectron microscopic technique was used to obtain morphological evidence for a role of oxytocin and vasopressin in the regulation of their own or each others release from the neural lobe. No synaptoid contacts of oxytocin- or vasopressin-containing axons with other neuronal structures were observed. However, synaptoid contacts of oxytocin- and vasopressin-containing nerve terminals and Herring bodies with pituicytes were frequently observed. These findings suggest that the pituicyte may participate in auto- and/or cross regulation of oxytocin and vasopressin release. Moreover, oxytocin and vasopressin precursor-derived peptides were found in the cytoplasm of some pituicytes, an unexpected finding that will be discussed. PMID- 8518940 TI - Sexual differences in N-methyl-D-aspartate receptor-mediated regulation of tuberoinfundibular dopaminergic neurons in the rat. AB - The purpose of the present study was to examine the effects of N-methyl-D aspartate (NMDA) receptor blockade on the activity of tuberoinfundibular dopaminergic (TIDA) neurons in male and female rats. TIDA neuronal activity was estimated by measuring either the accumulation of 3,4-dihydroxyphenylalanine (DOPA) 30 min after the administration of the decarboxylase inhibitor NSD-1015 or the concentration of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence. The non-competitive NMDA receptor antagonist MK 801 markedly reduced prolactin secretion in both male and female rats. MK-801 also produced a dose- and time-dependent decrease in the activity of TIDA neurons in female rats, but had no effect on the activity of TIDA neurons in either intact, orchidectomized or orchidectomized, testosterone-treated male rats. Removal of the tonic stimulatory effects of prolactin on TIDA neurons in female rats by immunoneutralization of endogenous prolactin failed to alter the responsiveness of TIDA neurons to the inhibitory effects of MK-801. On the other hand, MK-801 was unable to inhibit TIDA neurons in ovariectomized female rats, but the responsiveness of TIDA neurons to MK-801 in ovariectomized female rats was restored following estrogen replacement, even in the absence of prolactin. Like MK-801, the competitive NMDA receptor antagonist CGS-19755 produced a dose dependent decrease in TIDA neuronal activity in female rats, which was prevented in a dose-dependent manner by the NMDA receptor agonist D,L-(tetrazol-5-yl) glycine. Taken together, these results reveal a sexual difference in the responsiveness of TIDA neurons to NMDA receptor antagonists, and suggest that estrogen positively modulates NMDA receptor-mediated, tonic stimulation of TIDA neurons in female rats by a prolactin-independent mechanism. PMID- 8518941 TI - Calcitonin gene-related peptide (CGRP): immunocytochemical identification of a neuropeptide synthesised by ventral paraventricular magnocellular neurones in the sheep. AB - The distribution of calcitonin gene-related peptide (CGRP)-immunoreactive neurones was examined in the hypothalamus and pituitary gland of the short-term ovariectomised ewe. A large number of magnocellular CGRP-immunoreactive neurones were identified in the ventral paraventricular nuclei (PVN); few were found in the dorsal PVN and supraoptic nuclei. Parvicellular CGRP-immunoreactive neurones were identified in low density scattered throughout the preoptic region, anterior and basal hypothalamus and region of the stria terminalis. A dense CGRP innervation of the median eminence and neural lobe of the pituitary was observed. These observations reveal substantial species differences in CGRP immunoreactivity compared with the rat and show that magnocellular CGRP synthesising neurones in the sheep are essentially restricted to, and define, the ventral PVN. This suggests a functionally distinct role for this previously neglected division of the PVN within the ovine hypothalamo-neurohypophyseal system. PMID- 8518942 TI - Dopamine formation from L-dopa administered exogenously is independent of dopaminergic neuronal activity: studies with in vivo microdialysis. AB - Extracellular dopamine (DA) levels in the steady state were not detected in the hippocampus of rats where sparse dopaminergic innervations were demonstrated. However, following L-DOPA (100 mg/kg i.p.) administration, extracellular DA was detected. Although tetrodotoxin (TTX, 1 microM) failed to prevent this phenomenon, the striatal DA peak disappeared with the addition of TTX (5 microM) into the perfusate and reappeared following L-DOPA (100 mg/kg i.p.) administration. These findings suggest that DA synthesis from L-DOPA, administered exogenously, is independent of the existence of dopaminergic neurons and that outflow of newly synthesized DA into the extracellular space is not coupled to neuronal activity. PMID- 8518943 TI - Post-ischemic potentiation of Schaffer collateral/CA1 pyramidal cell responses of the rat hippocampus in vivo: involvement of N-methyl-D-aspartate receptors. AB - The present study examined the functional changes in the hippocampal CA1 pyramidal cell system in vivo occurring after 12-min forebrain ischemia in the rat. A population excitatory postsynaptic potential and orthodromic population spike of CA1 pyramidal cells to stimulation of the Schaffer collaterals were potentiated at 6-8 h post-ischemia. These changes were not associated with an increase in excitability of the CA1 pyramidal cells as evaluated from the antidromic population spike induced by alveus stimulation, suggesting the presence of an increased synaptic efficacy. The post-ischemic potentiation was prevented by pretreatment with the N-methyl D-aspartate (NMDA) receptor antagonist, MK801, in a dose-dependent manner. These findings suggest that 12-min forebrain ischemia in the rat activates NMDA receptors, which results in an increase in synaptic efficacy to the CA1 pyramidal cells at 6-8 h post-ischemia. PMID- 8518944 TI - Identification of premotor interneurons which project bilaterally to the trigeminal motor, facial or hypoglossal nuclei: a fluorescent retrograde double labeling study in the rat. AB - With the aid of a fluorescent retrograde double-labeling technique, we examined in the rat the distribution of single neurons which project bilaterally to one of the orofacial motor nuclei (the trigeminal motor, facial and hypoglossal nuclei) by branching axons. The results suggested that premotor interneurons were distributed most frequently in the medial part of the parvicellular reticular nucleus; such neurons were further scattered in the other regions of the medullary reticular formation, in the regions around the trigeminal motor nucleus, in the parabrachial area, and in the mesencephalic reticular formation. PMID- 8518945 TI - Internodal potassium currents can generate ectopic impulses in mammalian myelinated axons. AB - Positive clinical symptoms can arise from ectopic action potentials in several disorders of myelinated axons. Here we report that an elevated K+ concentration in the periaxonal, internodal space can cause internodal K+ currents to become excitatory, resulting in slow potential oscillations and associated bursts of ectopic spikes. Ectopic firing may therefore be favoured by conditions in which periaxonal K+ buffering is compromised. PMID- 8518946 TI - The distribution of the globus pallidus neurons with input from various cortical areas in the monkeys. AB - Single neuron activities of the globus pallidus were recorded in awake monkeys. Electrical stimulation of various cortical areas (the prefrontal, premotor, supplementary motor and arcuate premotor areas, and the motor cortex) inhibited spontaneous discharge of pallidal neurons. This inhibitory response was considered to be mediated through the striatum. Considerable number of pallidal neurons responded to the stimulation of more than one cortical areas. However, the neurons receiving inputs from the motor cortex and/or arcuate premotor area and those receiving inputs from the prefrontal, premotor and/or supplementary motor areas were segregated. The former neurons were located ventrolaterally in the caudal part of the globus pallidus, while the latter ones were located dorsomedially in the rostral part of the globus pallidus. PMID- 8518947 TI - Neuronal activity in the motor and premotor cortices before and after learning the associations between auditory stimuli and motor responses. AB - In order to assess the effect of learning a conditional motor task on set-related cells of the precentral cortex we recorded a total of 228 task-related cells in awake, behaving primate. A first sample of 54 set-related cells was recorded while the monkey was performing at 54.7 +/- 7.8% and a second sample of 119 set related cells was recorded at the same stereotaxic coordinates while he was performing at 77.2 +/- 8.7%. After the monkey had learned the association between an auditory signal and a motor response we found a significant increase in the proportion and activity of directional set-related cells in the premotor cortex. Furthermore the proportion of short-latency set-related cells was found to increase in this area. None of those changes were observed in the motor cortex. PMID- 8518948 TI - Corticotropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y. AB - Central administration of neuropeptide Y (NPY) exerts a potent orexigenic effect in rats, whereas injection of corticotropin-releasing factor (CRF) suppresses food intake. Anatomical evidence of NPY-containing terminals located in close proximity to CRF-containing neurons and terminals of the hypothalamus and amygdala suggests possible interactions of these neuropeptide systems in food intake regulation. The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia. Injection of a 250-ng dose of alpha-hel CRF within the paraventricular nucleus (PVN) of the hypothalamus significantly potentiated the feeding induced by a 500-ng dose of NPY injected into the same locus. In contrast, feeding induced by administration of the 500-ng dose of NPY into the ventromedial hypothalamus (VMH) was not modified by intra-VMH pre treatment with a 250-ng dose of CRF antagonist. No effects of NPY or alpha-hel CRF on feeding were observed after administration into the central nucleus of the amygdala. Systemic pre-treatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the function of CRF neurons in the PVN (100 micrograms/kg) enhanced feeding induced by intra-PVN administration of a 500-ng dose of NPY. These results suggest that hypothalamic CRF systems in the PVN exert inhibitory control over NPY-induced food intake. PMID- 8518949 TI - Characterization of neurochemical phenotypes in cultured hypothalamic neurons with immunohistochemistry and in situ hybridization. AB - The expression of neurochemical phenotypes was studied in long-term cultures of dissociated embryonic neurons from rat hypothalamus. With time in culture, these neurons establish a complex dendritic and axonal network, as indicated by staining with antibodies against microtubulin-associated protein (MAP2) and neurofilaments (SMI32 and SMI33) as well as GABA and glutamate decarboxylase mRNA immunoreactivity. Neurons expressing neuropeptide Y (NPY) mRNA and NPY peptide and opioid-like peptides as well as vasopressin were observed. Further, weakly acetylcholinesterase- and NADPH diaphorase (nitric-oxide synthase)-labelled neurons were present. In conclusion, the neurochemical phenotypes reported for hypothalamic neurons in vivo can be observed in these cultures. This indicates that the culture conditions allow morphological and molecular differentiation. These findings support the view that long-term hypothalamic cultures provide a valuable model for studying mechanisms of neurosecretion in hypothalamic networks. PMID- 8518950 TI - Plasma nerve growth factor access to the postnatal central nervous system. AB - The accessibility of macromolecules to the postnatal mammalian central nervous system is a subject of controversy and importance. One of the biologically important macromolecules in neural development, nerve growth factor (NGF), is thought to be unable to cross the blood-brain barrier in postnatal mammals. In this study, I125 labeled 7S NGF was systemically administered to postnatal rats and was found to accumulate in the brain in significant levels. In addition, brains from saline perfused rats contained intact 7S NGF as determined by gel autoradiography. Radiolabeled NGF was found to be localized to specific areas corresponding to p75 NGF receptor distribution in the hippocampus and cortex by autoradiography. Circulating plasma NGF has access to the developing postnatal neuraxis where it may exert a humoral trophic function. PMID- 8518951 TI - Lewis and Fischer rat strains display differences in biochemical, electrophysiological and behavioral parameters: studies in the nucleus accumbens and locus coeruleus of drug naive and morphine-treated animals. AB - In previous studies, we demonstrated that tyrosine hydroxylase and neurofilament proteins are regulated by chronic morphine and chronic cocaine treatments in the ventral tegmental area in Sprague-Dawley rats and that the inbred Lewis and Fischer 344 rat strains, under drug-naive conditions, show different levels of these proteins specifically in this brain region. In the current study, we compared Lewis and Fischer rats with respect to levels of adenylate cyclase, cyclic AMP-dependent protein kinase and G-proteins in the nucleus accumbens (NAc) and locus coeruleus (LC), brain regions in Sprague-Dawley rats where these proteins are regulated by chronic exposure to morphine or to cocaine. We found that levels of adenylate cyclase and cyclic AMP-dependent protein kinase activity are higher in the NAc and LC of Lewis rats compared to Fischer rats, whereas levels of Gi alpha and G beta were lower. These strain differences were not seen in several other brain regions analyzed and no strain differences were detected in levels of other G-protein subunits. Lewis and Fischer rats also differed in the ability of chronic morphine to regulate adenylate cyclase and cyclic AMP dependent protein kinase in the NAc and LC. In the NAc, chronic morphine increased levels of the two enzymes in the Fischer strain only, whereas in the LC chronic morphine increased levels of the enzymes in both strains, with more robust effects seen in the Lewis rat. To understand possible physiological consequences of these strain differences in the cyclic AMP pathway, we studied LC neuronal activity under basal and chronic morphine-treated conditions. LC neurons of Lewis rats showed higher spontaneous firing rates in brain slices in vitro than those of Fischer rats and also showed greater morphine-induced increases in responsiveness to bath-applied 8-bromo-cyclic AMP. These electrophysiological findings are generally consistent with the biochemical observations. Moreover, Lewis and Fischer rats displayed very different opiate withdrawal syndromes, with different types of behaviors elicited upon precipitation of opiate withdrawal with the opiate receptor antagonist, naltrexone. The possible relationship between these behavioral findings and the biochemical and electrophysiological data is discussed. These studies provide further support for the possibility that Lewis and Fischer rat strains provide a useful model system in which some of the genetic factors that contribute to drug-related behaviors can be investigated. PMID- 8518952 TI - A protease is recovered with a dimeric form of acetylcholinesterase in fetal bovine serum. AB - A protease activity which co-purified with affinity-purified fetal bovine serum acetylcholinesterase (AChE) has been shown to release the amyloid protein precursor (APP) of Alzheimer's disease from cell membranes. The nature of this protease and its relationship to AChE have not been established. In this study, the protease activity was found to be recovered with a minor dimeric form of AChE. This minor form (AChEII) was distinguished from the more abundant tetrameric form (AChEI) by a higher catalytic subunit relative molecular mass (M(r)) of 80,000 (80K), and by a lower affinity for edrophonium-Sepharose. The difference in subunit M(r) was due to differing degrees of glycosylation, as deglycosylation of both AChEI and AChEII gave rise to a similar subunit M(r) of 62K. The protease activity recovered with AChEII was not an intrinsic property of the esterase, as it was separated from the esterase by anion-exchange chromatography, and by immunoprecipitation with anti-AChE antibodies. AChEI possessed a similar subunit M(r) to the tetrameric form of AChE secreted from the bovine adrenal gland, while AChEII possessed a similar subunit molecular weight to the dimeric membrane-bound form of bovine erythrocyte AChE. Thus, it is possible that AChEII may be a solubilised form of a dimeric glycosylphosphatidyl inositol-linked AChE. PMID- 8518953 TI - Chronic pain increases brainstem proneurotensin/neuromedin-N mRNA expression: a hybridization-histochemical and immunohistochemical study using three different rat models for chronic nociception. AB - The role of neurotensin in the central nervous system is poorly understood. Exogenous neurotensin has potent antinociceptive effects when injected into the midbrain periaqueductal gray (PAG). Although it is present in terminals, fibers and perikarya within the PAG and other midbrain regions known for their antinociceptive circuits, it is not known whether endogenous neurotensin modulates nociception. We examined the midbrain in three different rat models for nociception to learn whether acute or chronic pain altered neuronal levels of the proneurotensin/neuromedin N mRNA (neurotensin mRNA). The models were: adjuvant induced polyarthritis, adjuvant-induced unilateral paw inflammation, and unilateral peripheral mononeuropathy caused by ligation of the sciatic nerve. Behavioral observations confirmed that the expected symptoms developed as previously described. Within each of the three experimental models, we performed in situ hybridization histochemistry on coronal sections from three midbrain levels that included the rostral one-third of the PAG, the middle one-third of the PAG, and the caudal one-third of the PAG. At the level of the rostral PAG, we found that neither chronic nor acute nociception altered the frequencies or distributions of neurons containing neurotensin mRNA. In contrast, at the levels of the mid- and caudal one third of the PAG, the early effects of the nociceptive lesions differed from the chronic effects. During the acute phase of each model, increases in either the frequency or field area of neurons that were hybridization-positive for neurotensin mRNA were confined to the ventromedial PAG and the dorsal raphe nucleus. As the nociceptive stimuli became chronic, the early increases in neurotensin mRNA-containing neurons at the level of the middle third of the ventral PAG were diminished but remained above control levels, while increases in neurotensin mRNA began to occur in the midbrain tegmentum lateral to the PAG. The most striking increases in neurotensin mRNA expression were observed 16-17 days after the onset of nociceptive stimuli. At the level of the mid-PAG and caudal PAG, increased hybridization signal intensities and neuron frequencies occurred within the nucleus cuneiformis and the lateral tegmental nuclei, including the pedunculopontine and microcellular tegmental nuclei, as well as the deep mesencephalic nuclei. Hybridization-positive neurons in the tegmental nuclei were not observed at early stages of lesion development, but were a consistent feature of caudal midbrains after nociception became chronic.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8518954 TI - Persistence of reorganized synaptic connectivity in the amygdala of kindled rats. AB - Kindling stimulation was applied to the basolateral amygdala of adult rats, and the density of dendritic synapses was examined under the electron microscope in the medial amygdaloid nucleus (MAN) contralateral to the site of stimulation, and an unfolding correction of biasedness was made. When generalized motor seizures had been induced for 5 days consecutively, the kindling was considered to be complete. The number of dendritic synapses, but not the number of somatic synapses, was markedly decreased in the MAN of the kindled rats. Reductions in numbers were marked in the case of both dendritic shaft and spine synapses. The reductions in numbers of shaft and spine synapses were similarly evident in the MAN of kindled rats 100 days after stimulation was discontinued. The numbers of dendritic synapses were similarly decreased in the rats that received additional bouts of stimulation subsequent to the completion of kindling. Thus, once the kindling was completed, the newly acquired synaptic connectivity was preserved in the MAN. These findings indicate that the remodeling of synaptic connectivity was a morphological correlate of the kindling in the MAN. PMID- 8518955 TI - The direct retinal projection to VIP neuronal elements in the rat SCN. AB - The connection between optic nerve terminals and vasoactive intestinal peptide (VIP)-containing neurons in the rat suprachiasmatic nucleus (SCN) was investigated using double labeling immunocytochemistry. Cholera toxin B subunit (CT) was injected into the right eyeball, and coronal sections of the SCN were then processed for CT immunocytochemistry with silver-gold intensification and VIP immunocytochemistry consecutively with DAB staining alone. In the ventrolateral portion of the SCN, CT immunoreactive (CT-IR) optic nerve terminals were found to make synaptic contacts not only with VIP-like immunoreactive (VIP LI) dendrites, but also with VIP-LI perikarya. CT-IR nerve endings were also found to make synaptic contacts with non-VIP immunoreactive neuronal dendrites. PMID- 8518956 TI - Dissociation of kainic acid lesion effects on the asymmetry of rotation and lateral head movements. AB - The present study tested the relationship between horizontal head movement asymmetry and rotation behavior after unilateral kainic acid (KA) lesions of the pontine reticular formation (PRF). In line with previous studies, the lesions decreased the rate of ipsilateral spontaneous head movements and spared contralateral spontaneous head movements. In contrast to previous studies, however, these lesions facilitated ipsilateral rather than contralateral rotation. Histological analysis revealed that the ipsilateral rotation may be accounted for by distant effects of the KA injection in the PRF on the ipsilateral substantia nigra (SN). We conclude that unilateral lesions consisting solely of the PRF lead to a preference for contralateral horizontal head movements which then channel rotated away from the lesioned side. KA injections in the PRF, however, are also associated with distant lesions within the ipsilateral extrapyramidal system which override the channeling effect of the contralateral head movements and induce instead ipsilateral rotation. PMID- 8518957 TI - Diurnal changes of GABA turnover rate in brain and pineal gland of Syrian hamsters. AB - Circadian rhythms of GABA turnover rate in cerebral cortex, preoptic area-medial basal hypothalamus (PMBH), cerebellum, and pineal gland were examined in Syrian hamsters kept for 3 months under either long (14 h of light/day) or short days (10 h of light/day). In vivo GABA turnover rate was measured by the increase of GABA levels following inhibition of GABA-transaminase by gamma-acetylenic GABA. Under long photoperiods, a significant rhythm of GABA turnover was detected in the four areas studied (cerebral cortex, PMBH, cerebellum, and pineal gland), with maxima at night. A Cosinor analysis indicated acrophases which varied from 2300 to 0400 h (3rd to 8th h of darkness). Under short photoperiods, there were no significant circadian variations in GABA turnover in the cerebral cortex, and the synchronization in turnover rate among the remaining regions was lost, with acrophases being detectable either during the light phase of daily photoperiod (PMBH) or at night (cerebellum, pineal gland). Steady state levels of GABA also changed periodically in the same brain regions under both lighting environments, although phase relationships of circadian rhythms in GABA content and turnover rate varied significantly among tissues, as well as on photoperiodic conditions. PMID- 8518958 TI - Oxytocin inhibits nonphasically firing supraoptic and paraventricular neurons in the virgin female rat. AB - Nonphasically firing activities were recorded from neurons in the supraoptic (s.o.) and paraventricular (p.v.) nucleus of the virgin female, male, and ovariectomized rat hypothalamic slice preparations. Following bath application of oxytocin (OXT), less than 1.0 x 10(-8) M, 24 (75%) of 32 virgin female s.o. neurons showed inhibitory responses and only one neuron showed excitatory response. In contrast to virgin female, five (63%) of eight male s.o. neurons were excited by OXT application. The same tendency was shown in the p.v. neurons. Among six s.o. neurons obtained from ovariectomized virgin rats, five neurons increased their firing rate to the application of OXT. After blocking synaptic transmission, the inhibitory responses of virgin s.o. neurons and the excitatory responses of ovariectomized virgin s.o. neurons to application of OXT were still observed with equal configurations. These findings suggest that the responses of nonphasic neurons to OXT may not due to synaptic drives. PMID- 8518959 TI - Heterogeneous characteristics of mitral cells in the rat olfactory bulb. AB - The spontaneous firing activity of olfactory bulb mitral cells and their response to intrabulbar infusion of GABAA receptor antagonist bicuculline were studied in ovariectomized, urethane-anesthetized female rats. Mitral cells recorded in the absence of specific stimuli and nasal airflow displayed three distinct patterns of spontaneous firing: high-frequency bursts with relatively long silent periods; high-frequency bursts without accurately defined silent periods; continuous. Infusion of bicuculline (0.2 nmol) into the bulb yielded inconsistent results on spontaneous firing and its inhibition evoked by electrical stimulation of the lateral olfactory tract. Of 32 cells tested, the spontaneous firing rate increased for 24, decreased for 6, and was not altered for 2. Likewise, of 18 cells tested, the poststimulus inhibitory period shortened for 12, lengthened for 4, and not altered for 2. An increased dose (0.4 nmol) of bicuculline produced dose-response relationships simply without any reversal effect. These results suggest that the heterogeneity of mitral cells exists in the context of local interneuronal circuitry in the bulb. PMID- 8518960 TI - Dural neuropeptide changes after subarachnoid hemorrhage in rats. AB - The effect of subarachnoid hemorrhage (SAH) on the neuropeptides and mast cells of the rat dura mater has not been reported. We examined the outcome of SAH on the rat supratentorial dura mater to determine whether dural nerves undergo effects similar to those of nerves accompanying cerebral blood vessels after SAH. Following the injection of fresh autologous arterial blood into the cisterna magna, animals were sacrificed at 6, 24, and 48 h, and 6 days post-SAH. Dural whole mounts were immunohistochemically reacted with antibodies to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and serotonin (5-HT). SP-like immunostaining was substantially reduced after SAH and subsequently returned to control levels at 6 days. NPY-like fiber innervation of the dura was markedly reduced after SAH; although immunostaining intensity increased, it had not returned to control levels at 6 days. The 5-HT content of dural mast cells identified by immunostaining markedly decreased at 6 and 24 h and returned to control levels at 48 h. In contrast, CGRP immunostaining was unchanged in all experimental groups. One possible explanation for this differential response is that subpopulations of trigeminovascular neurons containing SP, CGRP, or CGRP and SP respond differently to various stimuli, including SAH. Another possibility is a differential release of SP or CGRP from the same fiber. To the best of our knowledge this is the first documentation that the dura is also a target for intracranial pathological processes, such as SAH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518961 TI - Baroreceptor control of vasopressin-producing cells in streptozotocin diabetic rats. AB - Electrical activities of the vasopressin (AVP)-producing cell in the supraoptic nucleus of the streptozotocin diabetic (STZ-DM) rat were recorded extracellularly and compared with those in the control rat. Higher hematocrit (45.3 +/- 0.5%, mean +/- SE) and lower mean blood pressure (MBP) (89.5 +/- 2.1 mmHg) suggested that STZ-DM rats were hypovolemic and hypotensive. The mean discharge rates of AVP cells were 15.2 +/- 3.1 Hz (STZ-DM) (p < 0.05 vs. control) and 8.8 +/- 0.8 Hz (control), respectively. Pressor and depressor responses were caused by phenylephrine (1.5 and 2.9 micrograms/kg, i.v.) and nitroprusside (1.5 micrograms/kg, i.v.), respectively, during the recording the AVP cells. Pressor and depressor responses linearly (STZ-DM; gamma = -0.7071, control; gamma = 0.9262) decreased and increased the discharge activity of the cells in both experimental groups, respectively. The MBP-neuronal activity relationship in STZ DM did not differ statistically from that in the control. These results suggest that cardiovascular regulation of AVP release is well retained in STZ-DM rats. PMID- 8518962 TI - Ontogenic distribution of muscarinic receptors and acetylcholinesterase in the rabbit hippocampus. AB - Ontogenic development of muscarinic receptors was examined in the hippocampus of rabbits (from P2 to P60) using radioautographic method. Muscarinic sites were labelled with (3H)-quinuclinidyl-benzilate and pharmacologically defined M1 and M2 receptor subtypes with (3H)-pirenzepine and (3H)-oxotremorine, respectively. The distribution of binding sites was compared to acetylcholinesterase (AChE) staining in adjacent hippocampal sections. The two cholinergic components are progressively set up in the hippocampus during the first three postnatal weeks. The AChE staining was very low in all hippocampal fields in P2 rabbits. At P8 and after, the AChE staining was more pronounced in CA3 and CA4 than in CA1 and CA2. On the contrary, the M1 muscarinic binding sites were more abundant in CA1 and CA2 hippocampal fields than in CA3 and CA4 at all ages studied. M2 muscarinic binding sites were only distinguishable at P45 and have a relatively homogeneous distribution. This study shows a differential developmental evolution in the distribution of AChE and muscarinic M1 receptors, and no obvious correspondence between these two cholinergic markers was observed. PMID- 8518963 TI - Decreased seizure threshold after intrahippocampal colchicine injection in rats. AB - Wet dog shaking elicited by perforant path stimulation is little affected by bilateral injection of colchicine into the dorsal hippocampal formation but virtually eliminated by bilateral injection into the ventral hippocampal formation. Injection of colchicine into either dorsal or ventral hippocampal formation lowers the threshold for eliciting forelimb clonus with rearing. This effect is more pronounced 8 weeks postinjection than 2 weeks postinjection when colchicine is injected in the ventral hippocampal formation. This suggests that inappropriate reactive synaptogenesis and/or neuronal degeneration continues for an extended period after intrahippocampal injection of colchicine, especially in the ventral hippocampal formation. PMID- 8518964 TI - Hemodynamic stress activates locus coeruleus neurons of unanesthetized rats. AB - The effects of hypotensive stress elicited by nitroprusside infusion on discharge activity of noradrenergic locus coeruleus (LC) neurons of unanesthetized rats were characterized. Nitroprusside (75 micrograms/30 microliters/min, 15 min IV infusion) decreased mean arterial pressure of unanesthetized rats by 50 +/- 2 mmHg (n = 5). Simultaneous recordings of LC spontaneous discharge revealed an increase in discharge rate (197 +/- 87%) that was associated with hypotension. A lower concentration of nitroprusside (10 micrograms/30 microliters/min) that decreased blood pressure of halothane-anesthetized rats by 55 +/- 2 mmHg was much less effective in producing hypotension and did not increase LC discharge when administered to unanesthetized rats. Prior administration of the CRF antagonist, alpha helical CRF9-41 (50 micrograms, ICV) greatly attenuated LC activation by nitroprusside. These findings demonstrate that LC activation elicited by nitroprusside is dependent on the magnitude of hypotension. The present results also demonstrate that nitroprusside is a less potent hemodynamic challenge in unanesthetized rats. Finally, LC activation associated with nitroprusside administration to unanesthetized rats is mediated to a large extent by CRF, confirming findings in anesthetized rats. PMID- 8518965 TI - Confocal imaging of the retrograde tracer fluoro-gold using a non-ultraviolet laser. AB - Until now, Fluoro-gold confocal imaging has been problematic because it requires an ultraviolet laser. We describe here a practical method to visualize Fluoro gold in a confocal laser scanning microscope without an ultraviolet laser through an immunofluorescence procedure using antibodies against Fluoro-gold. PMID- 8518966 TI - [Graphical structuring of olfactory quality based on molecular parameters. Cases of experimental data from the Andre Holley group]. AB - Olfactory quality, measured by Holley and coworkers in a series of six studies on frog olfactory mucosa, is compared with two molecular parameters for the set of 75 stimulants studied. On this basis, 96% of the odorants, grouped in 11 olfactory clusters, are correctly discriminated. PMID- 8518967 TI - [Immunomodulatory and anti-oxidant effects of bovine lactoferrin in man]. AB - Lf presented differential effects in the induction of normal human monocyte activation. Lf inhibits the free radical generation by normal human monocytes in response to PMA. This effect on free radical generation is linked to the nature of the divalent cationic metal that substitutes the Apo-Lf. Indeed, the substitution of Fe2+ by another cationic transition metal (Cu2+, Zn2+, Pt2+ or Au2+) modifies the anti-oxidant effect of Lf. Among the different substituted Lf the Lf saturated with Cu2+ is the more potent inhibitor of free radical generation by normal human monocytes. In addition to its anti-oxidant effect, Lf stimulates, in combination with LPS, the production of cytokines (IL-1 beta, TNF alpha and IL-6) and of prostacyclin (PGI2) by normal human monocytes. This potentiating effect is independent of the cation that substitutes the Lf, since the Apo-Lf is able to induce such a potentiating effect. In addition, whereas Lf does not modulate the phenotype of normal human monocytes stimulated or not with IL-4 it does enhance the IL-4-induced release of the soluble form of CD23 by these cells. PMID- 8518968 TI - Effects of testosterone on triglyceride levels and fatty acid composition in the liver and serum of the rat. AB - Triacyglycerol content and fatty acid composition has been determined in the liver and in the serum of normal, castrated and testosterone-treated rats. Most variations were found in UNS/SAT ratio, which were referred to an action of the hormone on the delta 5-delta 6-delta 9 desaturases. Results concerning the behaviour of delta 9 desaturase suggest that either different isoenzymes are involved or that a single enzyme undergoes a different regulation according to the substrate involved. PMID- 8518969 TI - Mutagenicity of structurally related phenylazo-3-pyridines in Salmonella typhimurium. AB - Studies were conducted to explore structure-activity relationships for 4'-N,N dimethylamino-1'-phenylazo-3-pyridine and nine structurally related compounds in Salmonella typhimurium tester strains TA1535, TA100, TA1537, TA1538, TA98. Each compound was tested for mutagenicity at five or more concentrations that varied from 10-5000 micrograms/plate. We used the standard plate test and the investigations were carried out both in the absence and presence of Aroclor-1254 induced rat-liver homogenate and the components of the NADPH-generating system. Negative response was observed for 4'-N,N-dimethylamino-1'-phenylazo-3-pyridine and five of its analogues (4'-N,N-diethylamino-1' phenylazo-3-pyridine; 4'-N,N-di (beta-hydroxyethylamino)-1' phenylazo-3-pyridine; 4'-N-methylamino sulfonic acid 1'-phenylazo-3-pyridine; 4'-N,N-dimethylamino-6'-acetamido-1' phenylazo-3 pyridine, and 4'-N,N-di-(beta-hydroxyethylamino)-6'-methyl-l' phenylazo-3 pyridine). When S9 induced by Aroclor-1254 was present, the compound 4'-N,N dimethylamino-6-methoxy-1' phenylazo-3-pyridine exhibited mutagenic activity in the two strains TA1538 and TA98. The compound 4',6'-diamino-3-methyl-1'-phenylazo 3-pyridine was also mutagenic, both in the presence and in the absence of S9 mix. The two compounds 4'-N,N-dimethylamino-6-butoxy-1'-phenylazo-3-pyridine and 4'N,N di-(beta-hydroxyethylamino)-1'-phenylazo-3-[6-N,N-di-(beta- hydroxyethylamino) pyridine were either weakly mutagenic or nonmutagenic. On the basis of these data, it is concluded that the mutagenicity of phenylazo-3-pyridines, like monocyclic aromatic amines and azo dyes, is influenced by the nature of the substituent chemical groups and their positions in the molecular structure of the compounds. PMID- 8518970 TI - Cytoskeleton modifications induced by phenobarbital, 2-acetylaminofluorene and 4 acetylaminofluorene in normal and initiated/selected hepatocytes: relation with the "resistant" phenotype. AB - Initiated/selected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a non carcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the "resistant" hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubulin in ISH could thus be explained by the "resistant" metabolic profile of these cells. PMID- 8518971 TI - Flow cytometric analysis of the cell-cycle distribution of spleen lymphocytes isolated from Fischer 344 rats exposed to ethyl nitrosourea. AB - Current studies in our laboratory are designed to determine the frequency of genotoxic responses induced in lymphocytes isolated from Fischer 344 rats. To evaluate the effect of a model compound, N-ethyl-N-nitrosourea (ENU), on the cell cycle distribution of spleen lymphocytes, 8-week old, female Fischer 344 rats were injected i.p. with ENU and sacrificed 1, 2, 4, and 6 weeks after exposure. Four replicate cultures per dose per exposure period were established and cells were cultured for 66 hr. Colcemid, an agent which blocks cells in mitosis and induces an accumulation of cells in the G2 + M peak, was added to two of the four cultures as a positive control. After a 3 hr incubation, the cells were harvested, the nuclei stained with propidium iodide, and the DNA content of the individual nuclei was quantified by flow cytometry. As expected, exposure to Colcemid resulted in an accumulation of cells in the G2 + M phase of the cell cycle, which was accompanied by a decrease in the G0 + G1 population. The increase in the G2 + M population was significant (p < 0.05) in cultures of lymphocytes assayed at 4 and 6 weeks after exposure. The effect of increasing ENU concentration was an increase in the percentage of S-phase cells (p = 0.05) and a decrease (p < 0.02) in the percentage of G0 + G1 cells. This finding was observed only in those lymphocytes isolated 1 week after exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518972 TI - An in vitro system to screen for diarrheagenic chemicals. AB - We examined an in vitro system to screen for diarrheagenic chemicals using an established intestinal cell line (T84 human colonic carcinoma). The cells were grown on Millicell-PCF (polycarbonate membrane) wells. The cells were seeded at approximately 5 x 10(6) cells/30mm well and incubated for 9-11 days in a 5% CO2 incubator saturated with water at 37 degrees C. The culture medium was a 1:1 mixture of Ham's F12 and Dulbecco's MEM with 5% fetal bovine serum and 25 micrograms/ml gentamicin sulfate. The well containing cells was removed from the incubator and mounted in a modified Ussing chamber for measurement of short circuit current (ISC). Chemical-induced increases in ISC are usually indicative of electrogenic epithelial Cl- secretion, which is associated with diarrheagenic effects in animals and humans. T84 cells grown on Millicell-PCF membrane responded with an increase in ISC after basolateral addition of the cholinergic (muscarinic) agonist carbachol, prostaglandin E2, 16,16-dimethylprostaglandin E2, and forskolin, while non-diarrheagenic prostaglandin D2 did not affect ISC. Based on our results, this in vitro system has the potential to be adapted as a rapid screen for detecting diarrheagenic chemicals. PMID- 8518973 TI - Misidentification delusions, facial misrecognition, and right brain injury. AB - Individuals suffering from misidentification syndromes may present with right hemispheric pathology and deficits in facial recognition. In addition, misidentification delusions have been associated with aggressive behaviour. The possible linkage between misidentification phenomena, facial recognition, and aggression is discussed, illustrated by the case of a patient suffering from an organic delusional disorder. PMID- 8518974 TI - The benefits of clomipramine-fluoxetine combination in obsessive compulsive disorder. AB - We report the benefits of clomipramine-fluoxetine combination in four cases of severe obsessive compulsive disorder. In two cases, the combination was effective when either drug used singly was ineffective. In the other two cases, fluoxetine adjunct produced benefits with no additional side effects. PMID- 8518975 TI - Four cases of supposed multiple personality disorder: evidence of unjustified diagnoses. AB - Four cases are presented in which an unjustified diagnosis of multiple personality disorder was made. These cases are used to illustrate the concern that some cases of multiple personality disorder may be the result of misdiagnosis by both patients and clinicians. PMID- 8518976 TI - A diagnostic and therapeutic N-of-1 randomized trial. AB - The objective of this paper is to study the effect of amitriptyline on a young woman with symptoms of lightheadedness, palpitations, somnolence and fatigue. We conducted a single case (N-of-1) randomized trial including three pairs of treatment periods. Each pair included one four-week period when the patient was receiving amitriptyline and one four-week period when the patient was receiving placebo. The clinical setting was a secondary care internal medicine practice. During active treatment periods, amitriptyline was given in a dose of 100 mg each evening. Efficacy symptoms included lightheadedness, headaches and somnolence/fatigue. Side-effects of dry mouth and constipation were also monitored. Each symptom was rated on a seven point scale in which higher numbers denoted fewer symptoms. For the combined efficacy score, the mean difference in scores and the associated standard error was in favour of amitriptyline. The most profound effect was on sleepiness. These differences represent clinically important treatment effects. Dry mouth and constipation were worse on the active drug, but differences did not reach statistical significance. Our experience suggests the usefulness of N-of-1 randomized trials in outpatient medical practice, including psychiatric practice. PMID- 8518977 TI - Stability of borderline personality disorder. AB - This study examines the course of illness and stability of borderline personality disorder (BPD) in a group of inpatients seen at a two-year follow-up. The diagnosis of borderline personality disorder, as established by the use of the Diagnostic Interview for Borderlines, did not change in 39 of the 65 subjects (60%) studied. Subjects who continued to show evidence of borderline psychopathology experienced more acute episodes of illness during the follow-up period and tended to be more involved in substance abuse. Impulsiveness and young age when first psychiatric care was received significantly predicted the presence of BPD features at follow-up. PMID- 8518978 TI - [Oral examination for certification in psychiatry]. AB - This paper first describes interviewing techniques and oral presentations made by candidates to the examiners. It then describes the factors related to a failing score on the oral certification examination. The author draws conclusions regarding the difference between the corporation examination, which gives candidates the right to practise, and the Royal College examination or that of the American Board of Psychiatry and Neurology, where the candidates chose whether or not they wish to take the examination. PMID- 8518979 TI - Offenses and defenses against patients: a psychoanalyst's view of the borderline between empathic failure and malpractice. AB - The behaviour of physicians is increasingly coming under scrutiny and attack, both from patients and from institutions that represent the public interest. This social process is partly a necessary and healthy quest for healing and partly a retaliatory response to inevitable failures on the part of physicians to live up to the standards expected of them. The process can assume such ruthless and pervasive forms that physicians are becoming exposed to impossible demands and even abuse at the hands of those they are trying to help. As a result, many physicians become defensive, withdrawing from patient care or reasserting their own needs in regressive ways that further offend or injure their patients. This increases public anxiety and outrage resulting in regressive and even violent "solutions", creating a vicious cycle in which mutual trust and respect is eroded and true health eludes our grasp. Physicians who practise psychotherapy are particularly aware of such regressive emotional pressures and therefore their experience can be taken as a bellwether of social change. Stirred by recent encounters with colleagues who have undergone public inquisition, humiliation and punishment, and drawing on personal clinical experience with patients whose regressive self-expression could at times be considered "borderline", the author attempts to understand the nature of the emotional forces being experienced by members of the profession at large. As in therapy, so in social change; the outcome depends on how well we understand, contain and channel the powerful feelings that underlie whatever actions are taken.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8518980 TI - Treatment of non specific dyssomnia with simple stimulus control procedures in a child with Down's syndrome. AB - Nonaversive behavioural interventions were used successfully to treat a disrupted sleep pattern in a child with Down's syndrome. A quasi-experimental single-case design was employed to evaluate the treatment efficacy. During the first phase of treatment, the mother implemented a structured bedtime routine and the child was no longer allowed to engage in activities while in bed. During the second phase, a stimulus control paradigm was employed in which a nearly life-sized rag doll was substituted for the mother in bed. Finally, the mother gradually withdrew from the child's bed and room. During baseline, the child spent an average of only six percent of the night sleeping alone. By the second phase, this rose to a mean of 26%. By the end of treatment this was increased to a mean of 78.2%. The increase was accompanied by collateral decreases in crying and distress. Improvements were maintained at follow-up. PMID- 8518981 TI - [Review of Kleine-Levin syndrome: toward an integrated approach]. AB - Kleine-Levin syndrome is a characterized by a periodic hypersomnia crisis as well as dietary and variable significant psychic symptoms. Its rarity makes its definition and study complex. Many etiologies have been considered, especially regarding a hypothalamic dysfunction. Physiological, radiologic, anatomical and polysomnographic studies have not shown clearly conclusive results, but the syndrome appears to be related to affective disorders. This hypothesis is supported by the findings of a positive therapeutic response to lithium. However, we are interested in the related psychological factors, whether they are primary or secondary. A clinical case illustrates these factors, and a basic neuropsychiatric intervention concept is proposed. PMID- 8518982 TI - Cross-validating factors associated with discharges against medical advice. AB - Between six percent and 35% of psychiatric patients discharge themselves from hospital against medical advice (AMA). The discharges may prevent patients from deriving the full benefit of hospitalization and may result in rapid rehospitalization. We examined sociodemographic and clinical characteristics of 195 irregular discharges from a 237 bed psychiatric hospital over a five year period and found that AMA discharges increased over the study period to a peak of 25% in 1986. There was a strong negative correlation between AMA discharge rates and the willingness of physicians to commit patients involuntarily. Multiple discriminant analysis revealed a set of nine variables that accurately classified 78% of cases into regular or irregular discharge categories. Further analysis revealed that there are two distinct subgroups of patients who discharge themselves AMA: those who repeatedly left the hospital AMA in a regular "revolving back door" pattern and those who left AMA only once. The repeat group exceeded the one-time group in terms of prior admissions, appearances before review boards, and percentage of Natives. The repeat group also spent twice as long in hospital, and 27% were readmitted within one-week of the index AMA discharge. Less than three percent of the one-time AMA group was readmitted within a week. These results were cross-validated on a new sample of irregular discharges and matched controls. PMID- 8518983 TI - A comparison of the demography, clinical profile and treatment of adopted and non adopted children at a children's mental health centre. AB - A retrospective analysis of adopted and non adopted children attending a children's mental health centre between 1959 and 1973 indicated a higher than expected number of males and a significantly higher number of professional fathers than expected in the adopted group. A sub-group of adopted children identified as having learning problems by reports of the parents and teachers had a different pattern of test scores on the Wechsler Intelligence Scale for Children from a non adopted group, who were also selected for learning difficulties. On the parent's and clinician's ratings, the adopted group had more parent-identified hyperactivity symptoms and clinicians' diagnoses of hyperactivity. Treatment data indicated that they used more stimulant medication; this was particularly significant for the early adoptees. The early adoptees were considered to be more hyperactive by their parents than the late adoptees. The late adoptees were more impaired on psychometric testing than those placed early, before six months of age. These findings are discussed in relation to possible explanations for the higher than expected prevalence of adoptees seen in clinical populations. PMID- 8518984 TI - "Medicalizing" behaviour. PMID- 8518985 TI - Fluoxetine and sexual dysfunction. PMID- 8518986 TI - Electric stimulus energy and the clinical response to electroconvulsive therapy. PMID- 8518987 TI - Blue jay mania. PMID- 8518988 TI - Verapamil may cause depression. PMID- 8518989 TI - Situs inversus, developmental dyslexia and psychosis. PMID- 8518990 TI - Consent and the geriatric psychiatry home service team. PMID- 8518991 TI - A versatile, inexpensive, intuitive and simple system for computer-assisted instruction in radiology. AB - A system for constructing courseware in Radiology is described. It uses widely available, inexpensive hardware and software to produce material that is versatile and easy to use. The computer-naive student readily interacts with both text and images. We briefly describe the hardware, the software, the development process, and the different prototype applications developed at this time. PMID- 8518992 TI - Radiological presentations of Castleman's disease. AB - The radiographic appearances of three cases of Castleman's disease of hyaline vascular type are reported. CT demonstrated homogeneous masses with marked contrast enhancement. Calcification was seen in one, and associated lymphadenopathy was seen in two. All tumors were hypervascular with prominent tumor blush on angiography. Sonography showed the masses to be hypoechoic with hyperechoic spots. On MR imaging, all tumors had homogeneous architecture with hypointensity on T1-weighted images and hyperintensity on T2-weighted images. In tumors with above characteristics in areas where lymphoid tissue is normally found, Castleman's disease should be added to the list of differential diagnosis. PMID- 8518993 TI - Computed tomography of relapsing polychondritis. AB - The CT findings of a patient with relapsing polychondritis involving the larynx, tracheobronchial tree, and nasal cartilage are described. In the proper clinical setting, a characteristic constellation of findings when noted on CT can aid in differentiating this rare inflammatory disease from other causes of airway compromise. CT is the most useful imaging modality, because cartilage and soft tissue components are well visualized. If diagnosed early, appropriate treatment may prevent life-threatening airway obstruction. PMID- 8518994 TI - Radiological findings of retroperitoneal leiomyoma and leiomyosarcoma: report of two cases. AB - Radiologic findings in cases of retroperitoneal leiomyosarcoma and leiomyoma were reported. These cases showed very similar findings: irregularly marginated large masses with central cyst formation and no calcification on CT and ultrasonography. Angiography showed tumor vessels and tumor stains. Cystic region due to central necrosis or hemorrhage was the most prominent radiologic finding in these cases. However, it was difficult to distinguish leiomyosarcoma from leiomyoma on the basis of the radiologic findings alone. PMID- 8518995 TI - Absence of the septum pellucidum and related disorders. AB - We present an illustration of the spectrum of intracranial abnormalities associated with absence of the septum pellucidum to better define and illustrate this disorder. CT and 1.5 Tesla MRI examinations of fifteen patients with absence of the septum pellucidum were meticulously analyzed and correlated with clinical and laboratory studies. The findings were compiled and categorized based upon the presence and type of associated radiologic abnormalities. Absence of the septum pellucidum may occur as an isolated abnormality (n = 3). In most patients (n = 12), associated complex developmental abnormalities are present which include heterotopias, hypoplastic falx, ventricular clefts, encephalocele, small pituitary gland, small optic nerves and chiasm, and corpus callosal dysgenesis. Inferior pointing and a squared-off appearance of the frontal horns are frequently noted. These, or other, more severe ventricular configuration deformities are present in all patients. We have portrayed the complete range of findings associated with absence of the septum pellucidum using an illustrative approach to clarify the different patterns of radiologic abnormalities which may be seen with this complex entity. PMID- 8518996 TI - A method for three-dimensional prostate imaging using transrectal ultrasound. AB - This paper describes a method for forming three-dimensional images of the prostate using transrectal ultrasound. This method extracts three-dimensional images of the prostate from sets of two-dimensional ultrasound images obtained via a special-purpose transrectal ultrasound probe. Each two-dimensional image is segmented and the results used to form a three-dimensional image of the prostate. A method for segmenting two-dimensional images of the prostate based on the Laplacian-of-Gaussian edge operator is described. The three-dimensional imaging method described provides a new, noninvasive method for monitoring gland pathology during radiation therapy. PMID- 8518998 TI - The analysis of biological shape changes from multidimensional dynamic images. AB - A technique for modeling shape changes in a time series of biological images of arbitrary dimension is described. The technique consists of first segmenting the image to locate the specimen, and then parametrizing the specimen in the initial image with an orthogonal material coordinate system. The deformation of the material coordinate system caused by the changing shape of the specimen is then solved for by minimizing an energy functional. The energy functional is a linear combination of a brightness continuity term and a shape change term. A parameter lambda, weights the brightness continuity against the shape change smoothness. The best value to use for lambda is chosen as the value that minimizes the mean square error between the image derived from the calculated shape change parameters and the corresponding actual image. A two-dimensional implementation by finite differences is given. Results from both two-dimensional confocal images, and two-dimensional synthetic images are presented. Our early work on a three-dimensional implementation is given. PMID- 8518997 TI - CT-based radiotherapy treatment planning for cancer of the nasopharynx. AB - We analysed 32 cases of nasopharyngeal carcinoma (NPC) treated with radiotherapy trying to define the role of CT scan during radiotherapy planning, as well as radiation treatment and the follow-up of the patients. CT scan was found to help 15 cases with low-parapharyngeal involvement and/or bone erosion. Persistent abnormal CT findings at 2 mo after the end of radiation treatment were related to a 30% local recurrence rate. This rate went up to 100% in case of skull-base destruction. PMID- 8518999 TI - Nimodipine: cognition, aging, and degeneration. AB - Over the years, it has become apparent that many cytotoxic events employ a common pathway in destroying cells, namely the disruption of calcium homeostasis. Further studies show that the aging process is also accompanied, perhaps even partly caused, by changes in cellular calcium regulation. Finally, initial evidence has appeared in the literature showing that the Alzheimer beta-amyloid protein also interferes with calcium homeostasis. In these situations, the use of calcium antagonists, such as nimodipine, is expected to prevent part of the damage resulting from disrupted calcium regulation. Indeed, studies with nimodipine show that the compound reduces neuronal degeneration in a variety of toxic conditions. In addition, the compound has a functional effect in that it increases spontaneous neuronal firing of aged neurons, presumably by reducing the age-dependently increased afterhyperpolarization. Nimodipine also reduces age related perivascular anomalies and increases cerebral blood flow. A combination of these effects is probably why the substance is found to improve cognition in aged animals and in aged humans with impaired brain function. PMID- 8519000 TI - Assessing neuropsychological changes in pharmacological trials. AB - This article outlines the reasons that detection of subtle changes in the cognitive system is difficult in geriatric assessment. A new assessment approach is introduced that examines cognitive patterns and facilitates the evaluation of subtle changes. PMID- 8519001 TI - Clinical aspects of nimodipine. AB - This overview describes the result of the clinical development program in organic brain syndrome (impaired brain function in old age), where efficacy was proven in 11 double-blind, placebo-controlled studies. Another study within this development program showed nimodipine not only to be superior to placebo but also to hydergine. Furthermore, in a placebo-controlled clinical trial, nimodipine caused further improvement in performance compared to regular mental exercise at home. Due to the results in the organic brain syndrome program, registration was granted in 23 countries worldwide for this indication. In one clinical trial in the dementia development program, patients with dementia were carefully allocated either to primary degenerative dementia (PDD) or multi-infarct dementia (MID) stratum; nimodipine was shown to be superior to placebo independent of the etiology. Other clinical trials conducted in this indication supported the evidence for efficacy and showed that nimodipine-treated patients performed better than placebo patients. The safety profile of the drug is well established and substantiated by extensive postmarketing surveillance. In general, nimodipine was well tolerated, showing few adverse events. Finally, topics for future research are covered such as developing new instruments to assess more severe patients, expanding the patient collective to secondary dementias such as AIDS and Parkinson dementia, implementation of cost/utility elements in the development program, and the issue of nimodipine's potential role in the prevention of disease. PMID- 8519002 TI - Treatment of cognitive disturbances in old age: methodological and clinical aspects. PMID- 8519003 TI - Neuronal plasticity and function. AB - Neuronal plasticity is a key issue in neuroscience. It is defined as the capability of the neuron to adapt to a changing internal or external environment, to previous experience or to trauma. It appears that during all phases of the individual life span in the nervous system, changes take place that relate to development, degeneration, and regeneration. Growth cones are a focus of neuronal plasticity, and current views emphasize the importance of local intracellular [Ca2+] to the control of their function. Hence, outgrowth of neurites from neurons in culture may be manipulated by drugs that affect intracellular Ca2+ homeostasis. In the adult nervous system, much research deals with synaptic plasticity, especially with the activity-dependent changes seen after long-term potentation of hippocampal synapses. As in the growth cone, such changes involve Ca(2+)-dependent pre- and postsynaptic processes, among which is the activation of protein kinase C. During aging, Ca2+ homeostasis may be slightly disturbed over a long period of time that could result in loss of function seen after a short, toxic high level of intracellular [Ca2+]. In this respect, the beneficial effects of chronic treatment with the L-channel Ca(2+)-blocker nimodipine on sensorimotor function of aged rats is discussed. PMID- 8519004 TI - Atrial natriuretic peptide in congestive heart failure after acute myocardial infarction. AB - The concentration of atrial natriuretic peptide, a newly discovered hormone produced in the atrial wall, was measured in 55 patients during the first 72 h after acute myocardial infarction. 37 patients became clinically congested, while 18 patients avoided this complication. 13 patients (9 congested and 4 uncongested) experienced tachycardia, known to raise the concentration of atrial natriuretic peptide both with and without congestive heart failure. In the remaining 42 patients, the congested group had a significantly higher plasma atrial natriuretic peptide concentration than the uncongested group (p < 0.05) on all 3 days. In the congested group the concentration of atrial natriuretic peptide did not normalize after initiation of treatment. We conclude that the concentration of atrial natriuretic peptide is increased in all patients with acute myocardial infarction and that the level of atrial natriuretic peptide declines during the first 24 h in all patients and normalizes in the uncongested patients while the level of atrial natriuretic peptide is still elevated (at least for 72 h) in the congested patients. PMID- 8519005 TI - Plasma endothelin-1 levels in stable and unstable angina. AB - Plasma levels of endothelin-1 are elevated in acute myocardial infarction with higher levels in complicated infarctions. Measurements of levels in unstable angina could help clarify whether the elevation is the consequence of cell necrosis or is in some way related to the pathophysiology of acute coronary syndromes. Plasma endothelin-1 levels were determined by radioimmunoassay in 29 patients with unstable angina and 6 with a myocardial infarction. Blood samples were obtained at admission before drug administration and 6 and 72 h later. Levels were also determined in 27 control subjects and in 29 patients with stable angina. Admission levels were similar in unstable angina, 0.635 +/- 0.052 pg/ml [log(1 + x)], and myocardial infarction, 0.746 +/- 0.122, and significantly higher than in controls, 0.428 +/- 0.047, and stable angina patients, 0.449 +/- 0.052 (p < 0.01). In unstable angina, levels decreased progressively to normal at 6 h, 0.557 +/- 0.049 pg/ml, and 72 h 0.474 +/- 0.054, as opposed to an increase to 0.868 +/- 0.109 (p < 0.05) after 6 h in myocardial infarction followed by a decrease to 0.597 +/- 0.122 at 72 h. The elevation in unstable angina did not correlate with other clinical or laboratory characteristics. Unstable angina is associated with an increase in endothelin-1 plasma levels during the acute phase, suggesting a role of this endothelium-derived vasoactive peptide in the pathophysiology of acute coronary artery syndromes. PMID- 8519006 TI - Myofibrillar protein turnover in cardiac hypertrophy due to aortic regurgitation. AB - We recently demonstrated that total cardiac protein and myosin heavy chain fractional synthesis rates were not increased during the progressive cardiac hypertrophy that occurred 1 month following induction of aortic regurgitation. The increase in total cardiac protein and myosin heavy chain observed after 1 month of chronic volume overload was caused by a decrease in protein fractional degradation rates. The objective of the present study was to determine in vivo the relative contributions of protein synthesis and degradation of a variety of individual myofibrillar protein constituents, other than myosin heavy chain, to the left ventricular hypertrophic response to chronic aortic regurgitation. Intravenous infusions of [3H]-leucine were administered 3 days and 1 month following surgical induction of aortic regurgitation and sham operation in rabbits, and actin, myosin light chains 1 and 2, alpha-actinin and desmin fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Individual myofibrillar protein growth rates were determined from protein concentration and serial echocardiographic and postmortem left ventricular weight measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates. Individual myofibrillar protein content increased most rapidly during the 1st week and progressively increased at a slower rate between 1 week and 1 month, in parallel with increases in left ventricular weight. In comparison with sham operated controls, individual myofibrillar protein fractional synthesis rates were consistently increased at 3 days but not at 1 month. Progressive myocyte hypertrophy occurring at 1 month was caused by a decrease in myofibrillar protein fractional degradation rates. Increased myofibrillar protein synthesis contributed only to the early phase of myocyte hypertrophy while progressive hypertrophy in chronic aortic regurgitation was due to suppression of myofibrillar protein degradation. PMID- 8519007 TI - Oxygen demand-supply relationship in peripheral tissues as a therapeutic indicator in acute myocardial infarction with advanced heart failure. AB - Oxygen demand-supply relationships in peripheral tissues were studied in 14 patients who had acute myocardial infarction with advanced pump failure. Seven patients with acute myocardial infarction but without pump failure were studied as a control. In all patients, a Swan-Ganz catheter and a radial arterial cannula were inserted for the purpose of hemodynamic monitoring, and arterial and mixed venous blood were sampled. Initially, oxygen delivery (DO2) (p < 0.01) was lower, and oxygen extraction ratio (OER) (p < 0.001) and oxygen tension at 50% saturation (P50) (p < 0.01) were higher in patients with pump failure than in the controls. During the therapeutic course, with an increase in the cardiac index and DO2, oxygen uptake (VO2) did not change but OER (p < 0.001) and P50 (p < 0.01) significantly decreased in 6 survivors with pump failure. In contrast, an increased VO2 (p < 0.01) and no change of OER and P50 were observed in 8 nonsurvivors with pump failure. These results suggest that reversibility of oxygenokinetics might be an important factor for recovery from critical heart failure. PMID- 8519008 TI - Long-term cardiac mortality in patients admitted with noncoronary chest pain under suspicion of acute myocardial infarction. AB - The long-term prognosis for cardiac death was prospectively evaluated in three subpopulations admitted to a coronary care unit with chest pain under suspicion of acute myocardial infarction (AMI) with (1) confirmed AMI (n = 275), (2) AMI ruled out, but suspicion of coronary artery disease (n = 257) and (3) AMI ruled out and an obvious noncoronary reason for chest pain (n = 63). The latter subgroup included patients with pericarditis, valvular disease, arrhythmia, pneumonia, pulmonary embolism, gastric ulcer and musculoskeletal disorders. The 7 year cardiac mortality rates of the three subpopulations were 34, 17 and 32%, respectively (p < 0.0001). Despite the 'benign' nature of the chest pain, the cardiac mortality was high in all diagnostic categories of noncoronary chest pain. In conclusion, patients admitted with chest pain of apparently noncoronary origin are at high risk for later cardiac death. This indicates the presence of severe coronary artery disease in some of the patients. Consequently, all patients with chest pain and AMI ruled out should be evaluated carefully regarding coronary artery disease at the time of discharge. PMID- 8519009 TI - Acute myocardial infarction without warning: clinical characteristics and significance of preinfarction angina. AB - We investigated the clinical characteristics of acute myocardial infarction (AMI) not preceded by angina in 256 patients with first AMIs. Complications, including sustained ventricular tachycardia or ventricular fibrillation, pump failure and cardiac rupture, were more frequent in patients with AMI not preceded by angina (group 1, n = 92) than those preceded by angina (group 2, n = 164). The in hospital mortality rate was higher in group 1 than in group 2. Poor preexisting collateral channels or lack of ischemic preconditioning may be responsible for the poorer outcome in group 1 patients. PMID- 8519010 TI - Effect of subadipose tissue on the variables of signal-averaged electrocardiograms in healthy subjects. AB - Ventricular late potentials are obtained by signal averaging of surface electrocardiograms. Late potentials have been reported to be affected by body size or left ventricular mass. However, the effect of subadipose tissue, which is known to influence QRS amplitudes of surface ECG, on the variables of late potentials has not been evaluated. The relationships between the variables of late potentials and various obesity indices were assessed in 45 men, aged 24-38 years, without structural heart disease and bundle branch blocks. QRS duration, root mean square voltage in the last 40 ms and low-amplitude signals < 40 microV were obtained by signal-averaged ECG. Left ventricular mass was determined by echocardiography. QRS duration and root mean square voltage had no correlation with body height, weight, body mass index, sum of skin folds (triceps and subscapular) or left ventricular mass. Positive linear correlations were found between low-amplitude signals and weight (r = 0.48, p < 0.002) body mass index (r = 0.54, p < 0.002), sum of skin folds (r = 0.57, p < 0.002), percent body mass index (r = 0.54, p < 0.002). Subadipose tissue may shift the onset of the 40 microV point of low-amplitude signals to the left with a consequent prolongation of low-amplitude signals by attenuation of the QRS complex. These data suggest that the use of low-amplitude signals alone or as a combination in an obese population for the definition of positive late potentials is inappropriate. The low-amplitude signal has to be used with caution in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519011 TI - Electrocardiographic findings of left, right and septal hypertrophy in athletic students and sedentary controls. AB - We have previously demonstrated increased voltage of septal, right and left ventricular depolarization in 1,299 athletic students compared to 151 sedentary controls. In the present investigation we have studied the prevalence of hypertrophy and the correlation between hypertrophy and other ECG findings. An increase of Q waves of more than 0.2 mV was associated with increased indices of right and left ventricular hypertrophy. Right ventricular hypertrophy was associated with an increased prevalence of incomplete right bundle branch block and increased parameters of septal and left ventricular hypertrophy. Left ventricular hypertrophy was associated with increased indices of septal and right ventricular hypertrophy and with bradycardia. Furthermore, left ventricular hypertrophy was characterized by ST elevation and increased T wave amplitudes, but not by repolarization abnormalities. Thus, our data point to a harmonious hypertrophy. Based on our findings we suggest the following normal limits in young people (20-30 years) according to the 97.5 percentile regarding the Sokolow index: for athletic students 5.3 (males) and 3.6 mV (females), for sedentary controls 4.0 (males) and 3.6 mV (females). It remains to be clarified whether these values are also valid in top athletes. PMID- 8519012 TI - Electrocardiographic and echocardiographic findings in top athletes, athletic students and sedentary controls. AB - Thirty top level athletes, 30 athletic students and 30 sedentary controls underwent electrocardiographic and echocardiographic investigation. Resting ECG in athletes showed increased indices of hypertrophy compared to controls. The echocardiographic examination demonstrated an increase in left ventricular mass (LVM) of 47% in top athletes and 23% in athletic students compared to controls. The relationship between wall thickness and diameter was similar in all groups, as were parameters of systolic and diastolic left ventricular function at rest. There was no correlation between LVM assessed by echocardiography and ventricular ectopic activity assessed by Holter monitoring in this normotensive population. Highly significant correlations between ECG and echocardiographic parameters of hypertrophy were demonstrated. PMID- 8519013 TI - Free radical markers in patients with angina pectoris and normal coronary angiograms. AB - Markers suggestive of enhanced free radical (FR) activity have been demonstrated in patients with chest pain and normal coronary angiograms. This may be of pathogenetic importance because FRs impair vascular relaxation and are generated following episodes of myocardial ischaemia/reperfusion. Fifteen patients with angina pectoris, normal coronary angiograms and either a positive exercise tolerance test and/or abnormal dipyridamole thallium tomogram were studied along with 15 age-, sex- and smoking-matched controls. A peripheral venous blood sample was obtained to measure the following FR markers: malondialdehyde, plasma thiols, red blood cell glutathione and superoxide dismutase. No significant differences were detected in the levels of any of the FR markers between either the group of 15 patients with chest pain and normal angiograms or the subgroup with positive exercise tolerance tests when compared to the controls. There is therefore no evidence of enhanced FR activity in patients with chest pain and normal coronary angiograms in peripheral venous blood samples. PMID- 8519014 TI - Left ventricular dynamics during strenuous isometric exercise in marathon runners, weight lifters and healthy sedentary men: comparative echocardiographic study. AB - Global and segmental left ventricular dynamics during strenuous large-muscle isometric exercise were compared between endurance and static type professional athletes and sedentary men. Using a trunk dynamometer and supine echocardiography, only the weight lifters manifested increased (p < 0.01) wall thickness during both diastole and systole, resulting in decreased left ventricular volume at end systole. These group-related differences would suggest a causal relationship between chronic intensive weight-lifting training and efficient myocardial dynamics at the time of strenuous isometric exercise. PMID- 8519015 TI - [Practical problems in treatment of hypertension]. PMID- 8519016 TI - [Angiotensin-converting enzyme inhibitors in treatment of hypertension. Part 1. Emphasis on cilazapril]. PMID- 8519017 TI - [Characteristics of left ventricular systolic and diastolic functions in patients with essential hypertension]. PMID- 8519018 TI - [The role of angiotensin converting enzyme inhibition for therapy of patients with hypertension and heart failure]. PMID- 8519019 TI - [Hypertension, left ventricular hypertrophy and cardiovascular morbidity and mortality]. PMID- 8519020 TI - [Acute and chronic modification by cilazapril in comparison with hydrochlorothiazide on diastole heart function in hypertensive patients]. PMID- 8519021 TI - [Left ventricular hypertrophy in spontaneously hypertensive rats: effect of angiotensin converting enzyme inhibitors on morphologic ultrastructure]. PMID- 8519022 TI - [Correlations between arterial hypertension and sleep apnea]. PMID- 8519023 TI - [Does placebo lower nocturnal blood pressure in sleep-related respiratory disorders and arterial hypertension?]. PMID- 8519025 TI - [Angiotensin-converting enzyme inhibitors in the treatment of hypertension. Part 2. Emphasis on cilazapril]. PMID- 8519024 TI - [First dose response to cilazapril after discontinuation of metoprolol in hypertensive patients]. PMID- 8519026 TI - [Therapy conversion to cilazapril in angiotensin conversion enzyme inhibitor induced cough. Evaluation of the effect]. PMID- 8519027 TI - [Anti-ischemia effects of cilazapril in hypertensive patients, with simultaneous angina pectoris. Preliminary report of a pilot study]. PMID- 8519028 TI - [Changes in the left ventricular mass, wall tension and left atrial filling in long-term antihypertensive therapy. A comparative study with cilazapril and a thiazide diuretic]. PMID- 8519029 TI - [Effect of cilazapril on myocardial contractility and left ventricular systolic function in hypertensive patients with coronary heart disease and low ejection fraction]. PMID- 8519030 TI - [Angiotensin converting enzyme inhibitor-induced cough: patterns and incidence. Consequences for continuation of therapy]. PMID- 8519031 TI - [Antihypertensive effect of once daily 2.5 mg cilazapril in patients responsive to ACE inhibitors: evaluation by 24-hour ambulatory blood pressure monitoring]. PMID- 8519032 TI - [2.5 and 5 mg cilazapril once daily in comparison with placebo in hypertension. A comparative study with ambulatory 24-hour monitoring]. PMID- 8519033 TI - [Arterial hypertension and left ventricular dysfunction: pathophysiology, diagnosis and therapy]. PMID- 8519034 TI - Fluoxetine: a five-year review. AB - Depression is associated with significant morbidity, mortality, and economic cost. Although effective pharmacologic therapy has been available for nearly 40 years, most patients have been treated inadequately. The side effects associated with available antidepressants usually led to subtherapeutic dosing, premature discontinuation of therapy, or lack of patient compliance. The introduction in 1988 of fluoxetine hydrochloride, the first selective serotonin uptake inhibitor (SSUI) or selective serotonin reuptake inhibitor (SSRI) available in the United States, represented a major advance in the pharmacologic management of depression. Large-scale trials showed fluoxetine to be as effective as existing agents, but because of its selectivity, the side effects of fluoxetine treatment are generally mild and transient and rarely cause premature discontinuation of therapy. In clinical trials approximately twice as many patients discontinue treatment because of side effects with tricyclic antidepressants (TCAs) as with fluoxetine. In contrast to older agents fluoxetine requires no titration and can be dosed once daily. It is also safer in overdose than TCAs. Numerous clinical trials and widespread postintroduction clinical experience have demonstrated the advantages of fluoxetine compared with older antidepressants. It may also have some advantages over the two SSUIs that have followed thus far, sertraline and paroxetine, although comparative trials will be required to resolve this issue. PMID- 8519035 TI - The role of anaerobic bacteria in human infections. AB - Anaerobes are generally accepted as clinically important pathogens. Although they are found on most mucocutaneous surfaces, anaerobic bacteria are especially abundant in the upper and lower respiratory tracts, gastrointestinal tract, and female genital tract. They are involved in infections such as chronic sinusitis, aspiration pneumonia, lung abscess, intra-abdominal abscess, bacterial vaginosis, decubitus ulcer, and bite wounds. Depending on the type and location of the infection, treatment may involve surgical drainage and a multiple antibiotic regimen that provides protection against both anaerobes and gram-negative aerobes. Penicillin was the drug of choice for anaerobic infections, but its inactivity against most penicillinase-producing anaerobes has made it less useful for empiric therapy. Clindamycin, with its proven activity against anaerobic infections, is the current drug of choice. Clindamycin is particularly effective against upper and lower respiratory tract infections and infections of the female genital tract. PMID- 8519036 TI - Treatment of post-transplant diabetic patients. AB - Renal failure and the need for renal transplantation are more prevalent among patients with diabetes than among other patient groups. Immunosuppressive treatment regimens for post-transplant patients are reviewed, with special emphasis on diabetic patients. The major drugs used are cyclosporine, corticosteroids, azathioprine, antithymocyte or antilymphocyte globulins, and muromonab-CD3 (a monoclonal antibody). Their mechanisms of action, drug interactions, clinical uses in transplantation, and toxicity are reviewed. Some of these drugs will change a diabetic patient's requirements for insulin or oral hypoglycemic agents, and glycemic control during the post-transplant period needs careful monitoring. PMID- 8519037 TI - Total parenteral nutrition: clinical considerations. AB - Nutritional support is recognized as an important therapeutic intervention to promote wound healing sustained traumatically, surgically, or caused by chronically debilitating illness, and as an adjunctive therapy in patients with life-threatening infectious diseases. The total parenteral nutrition (TPN) formulation should be carefully tailored to meet the needs of each individual patient. Factors important in determining the TPN formula include nutritional assessment; total volume; duration of therapy; solution compatibilities; and disease-specific clinical considerations. TPN should be employed for patients who are unable to or should not consume nutrients via the gastrointestinal tract and patients who cannot consume enough nutrients to sustain nutritional requirements. Patients need not be malnourished to qualify for TPN. The provision of nutritional support requires calculation of basic components of the normal diet, including water, carbohydrate, fat, protein, electrolytes, vitamins, and trace elements. The total daily expenditure of calories can be calculated as a multiple of the patient's basal energy expenditure. Disease-specific considerations may require alterations in the amount of protein provided and the percentage of dextrose and fat calories utilized. PMID- 8519038 TI - Characteristics of the effects of the angiotensin converting enzyme inhibitor cilazapril on diurnal blood pressure. AB - Patients with stage I or II essential hypertension were assigned to receive 1 mg of cilazapril once daily in the morning (n = 11; mean age, 63 years); 2 mg of cilazapril once daily in the morning (n = 8; mean age, 60 years); or 1 mg of cilazapril twice daily (n = 9; mean age, 68 years). Blood pressure was recorded for 24 hours before treatment began and after 2 weeks of treatment. After all three doses of cilazapril, both systolic and diastolic blood pressures were lower than before treatment. Greater reductions in blood pressure were found after 2 mg of cilazapril daily than 1 mg daily. The antihypertensive effect of cilazapril was greater during the daytime than during the night. When the blood pressure effect was analyzed by the cumulative percentage method, it was noted that, after the two once-daily regimens, the magnitude of the blood pressure reduction was greater at higher blood pressures and smaller at lower blood pressures. No such trend was apparent after the twice-daily dose of cilazapril. PMID- 8519039 TI - Effects of amlodipine on platelet aggregation and blood pressure in patients with essential hypertension. AB - Ten patients (mean age, 46 years) with mild to moderate hypertension received 5 mg of amlodipine daily for 12 weeks. The amlodipine dose was increased to 10 mg daily in 4 patients whose blood pressure remained > or = 90 mmHg during the first 8 weeks. After 8 and 12 weeks of treatment, mean blood pressures in the supine, sitting, and standing positions and after exercise were reduced significantly. Heart rate did not change significantly from before to after treatment. Six hours after amlodipine administration, however, slight but significant increases in heart rate were noted at rest and after exercise. Platelet aggregation induced by adenosine diphosphate or collagen was significantly reduced 6 hours after amlodipine. One patient reported headache after the 10-mg dose of amlodipine. No other side effects were noted. It is concluded that 10 mg of amlodipine once daily is safe and effective in the treatment of mild to moderate hypertension. PMID- 8519040 TI - Endoscopic comparison of three aspirin preparations and placebo. AB - Eighty of 84 volunteers aged 22 to 70 years successfully completed a 3-month, single-blind endoscopic study in which they received single-dose placebo or 325 mg/day of enteric-coated aspirin (ECA), buffered aspirin (BA), or plain aspirin (ASA). Upper endoscopy was performed at the beginning of the study and after 4, 8, and 12 weeks. The gastric and duodenal mucosa was scored endoscopically using a system adapted from Lanza et al. Enteric-coated aspirin and placebo were not statistically different from one another in the gastric damage produced, but both were significantly different from ASA and BA. Significant damage to the gastric mucosa was seen with ASA and BA, with no significant difference between them. Analysis of duodenal mucosa injury revealed that BA, ECA, ASA, and placebo were not significantly different from one another. In addition, a statistical relationship between age and injury could not be proven. PMID- 8519041 TI - Use and acceptance of ventolin Rotacaps and the Rotahaler in 1235 asthmatic patients. AB - This open-label study was performed to characterize the acceptance, reliability, and adverse event profile of a dry powder delivery system for albuterol. A total of 1235 asthmatic outpatients, aged 11 to 84 years, were studied for 1 month. Each patient enrolled was documented as having a specific complaint concerning the use of a standard metered-dose inhaler. At the end of 4 weeks of treatment, the patients completed a questionnaire to record their opinions and preferences. The results were as follows: 93% stated that Rotacaps were easy to use; 92% that they could use Rotacaps during an asthma attack; 99% that they had no problems with breakage of the device; 94% that the drug tasted pleasant or had no taste; 70% that they could inhale a full dose with one breath; and 79% that Rotacaps were at least as effective as the metered-dose inhaler they had used previously. Drug-related adverse events were reported by 6% of the patients; no single event was reported by more than 1% of the patients. The results indicate that Rotacaps are a safe, effective, and well-accepted alternative to metered-dose inhalers in asthmatic patients. PMID- 8519043 TI - Treatment of severe, resistant familial combined hyperlipidemia with a bezafibrate-lovastatin combination. AB - Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by high levels of cholesterol, triglycerides, or both. The basic metabolic abnormality is overproduction of apolipoprotein B-100. High atherogenicity has been attributed to all forms of FCHL. We evaluated combined bezafibrate lovastatin therapy in 10 patients (9 men and 1 woman) with FCHL and markedly high cholesterol and triglyceride levels who were at high risk of coronary artery disease and who had not responded to diet and bezafibrate treatment alone. Eight patients had coronary artery disease, 6 had hypertension, and 3 had noninsulin dependent diabetes mellitus. Lovastatin 20 mg/day was added to the bezafibrate 600 mg/day regimen for 6 weeks; the lovastatin dosage was then doubled to 40 mg/day for an additional 6 weeks. The addition of 20 mg of lovastatin resulted in decreases of 15%, 20%, and 13% in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, respectively. Increasing the dose of lovastatin to 40 mg resulted in further moderate decreases of 4%, 3%, and 8% in total cholesterol, LDL cholesterol, and triglycerides, respectively, compared with the 20 mg/day dosage. Although previous reports have emphasized the potential side effects of combination treatment with lovastatin and fibric acid derivatives, our patients tolerated the regimen well, with no significant subjective complaints or laboratory abnormalities. The bezafibrate-lovastatin combination is a possible therapeutic option for severe, resistant FCHL, but close medical supervision is needed because of potential side effects. PMID- 8519042 TI - Circadian blood pressure change after carteolol chloride in younger and older hypertensive patients. AB - To determine whether there is an age-related difference in circadian blood pressure changes after administration of a beta-adrenergic blocker, 24-hour ambulatory blood pressure was measured before and after administration of long acting carteolol, a beta-blocker with intrinsic sympathomimetic activity, in 9 younger and 13 older hypertensive patients. Ambulatory blood pressure was measured noninvasively using an ambulatory blood pressure monitor every 30 minutes for 24 hours before and 8 weeks after a once-daily administration of 15 mg of carteolol. Systolic and diastolic blood pressure in the office significantly decreased in both groups after 8 weeks of carteolol treatment. The whole-day systolic and diastolic blood pressures also fell significantly after carteolol treatment in both groups. Carteolol reduced systolic and diastolic blood pressures during the day in both groups. However, no reduction was observed in nighttime systolic blood pressure in either group, although nighttime diastolic blood pressure tended to decrease in the younger group (P = 0.051). The pulse rate during the night significantly increased in both groups, although no change was observed during the day in either group. We conclude that the antihypertensive effect of carteolol on the circadian blood pressure pattern in younger and older hypertensive patients is comparable. Carteolol reduced only daytime blood pressure while hardly affecting the nighttime blood pressure in both groups. PMID- 8519044 TI - Enalapril and enalapril-hydrochlorothiazide in the treatment of essential hypertension. The Enalapril-Hydrochlorothiazide in Essential Hypertension Canadian Working Group. AB - A total of 217 patients with essential hypertension were enrolled by 25 Canadian centers in this double-blind, parallel study to compare the efficacy and safety of enalapril administered alone or in combination with hydrochlorothiazide. After a 4-week placebo period, patients were given 10 mg of enalapril for 2 weeks. At the end of the 2 weeks of therapy, patients were maintained on the same dose of enalapril, titrated to a higher dose of enalapril, or received combination therapy with hydrochlorothiazide if their diastolic blood pressure remained > 90 mmHg. Patients in group 1 received enalapril 10 mg or 20 mg and those in group 2 received enalapril 10 mg alone or combined with hydrochlorothiazide 25 mg. The maintenance phase lasted 8 weeks. A standard mercury sphygmomanometer was used to measure blood pressure at each visit. The mean decrease in supine diastolic blood pressure (SDBP) was 16 mmHg in groups 1 and 2; the mean decrease in supine systolic blood pressure (SSBP) was 19 mmHg in group 1 and 20 mmHg in group 2. Eighty percent of the patients in group 1 and 81% of those in group 2 had an SDBP < or = 90 mmHg at the final visit. To achieve this control, 67% of the patients received enalapril 10 mg and 33% received enalapril 20 mg in group 1. In group 2, 70% of the patients received enalapril 10 mg and 30% received enalapril 10 mg plus hydrochlorothiazide 25 mg. Eighteen patients in group 1 and 17 patients in group 2 experienced one or more minor adverse events. The most frequently reported adverse events were headache, asthenia, abdominal pain, nausea, and dizziness. No major adverse events were observed. We conclude that enalapril used alone reduces blood pressure in the majority of patients with mild to moderate essential hypertension. When blood pressure is not controlled by enalapril alone, hydrochlorothiazide can safely be added to the regimen. PMID- 8519045 TI - Probucol therapy in the prevention of restenosis after successful percutaneous transluminal coronary angioplasty. AB - The effect of probucol, a drug that inhibits the secretion of smooth muscle cell derived growth factor, was evaluated in the prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA). In 67 patients who successfully underwent prospective PTCA for the first time, the effects obtained in 31 patients given 750 mg or 1000 mg of probucol daily (group P) were compared with those in 36 patients given 150 mg of dipyridamole daily (group D). Drug treatment was initiated at least 7 days before PTCA and was continued for 3 to 6 months after PTCA, at which time a follow-up angiography was performed. There were no significant differences in patient characteristics (age, sex, pre-PTCA severity of angina pectoris), the number of affected vessels undergoing dilatation, or the residual degree of stenosis. The restenosis rate was significantly lower in group P (6 cases, 19.4%) than in group D (15 cases, 41.7%). In the nonrestenosis subgroup, the degree of stenosis progressed from 28.0 +/- 13.9% just after PTCA to 32.4 +/- 20.5% at follow-up angiography in group P, while it progressed significantly from 28.6 +/- 15.6% to 40.1 +/- 21.2% in group D (P < 0.05). A significant drop in serum cholesterol was observed in group P. The restenosis rate was lower in patients with high cholesterol levels at PTCA. No adverse reactions were noted in any patient. We conclude that probucol is effective in preventing restenosis after PTCA. PMID- 8519046 TI - Effects of cimetidine and ranitidine on the pharmacokinetics of a chronotherapeutically formulated once-daily theophylline preparation (Uniphyl). AB - The effects of cimetidine and ranitidine on the steady-state pharmacokinetics, safety, and efficacy of a chronotherapeutically formulated (CTF), once-daily theophylline preparation (Uniphyl) were evaluated in 12 adult patients with asthma. In this randomized, double-blind, three-way crossover study, patients received a fixed dose of CTF-theophylline and concurrent cimetidine, ranitidine, or placebo for a period of 7 days each. Asthma symptoms, drug side effects, and beta 2-agonist inhaler use were recorded daily. Venous blood sampling for pharmacokinetic assessment was done over a complete dosing interval on day 7 of each phase. Coadministration of cimetidine, but not ranitidine, was associated with a significant decrease in the apparent oral clearance of theophylline (2.47 +/- 0.91 vs 1.85 +/- 0.63 L/hr; P = 0.004) and increases in the theophylline area under the curve (233.48 +/- 58.99 vs 307.43 +/- 79.07 mg/L/hr; P = 0.003), peak concentration (13.2 +/- 2.8 vs 16.7 +/- 3.7 mg/L; P = 0.002), and trough concentration (6.4 +/- 2.5 vs 9.0 +/- 3.0 mg/L; P = 0.008). Despite the changes in theophylline pharmacokinetic parameters during cimetidine treatment, no significant differences in asthma symptom scores or side effects were seen when once-daily CTF-theophylline was administered concomitantly with cimetidine, ranitidine, or placebo. PMID- 8519047 TI - Mental deterioration in old age: results of two multicenter, clinical trials with nimodipine. The Nimodipine Study Group. AB - The efficacy and tolerability of nimodipine, a calcium antagonist selective for the central nervous system, was evaluated in old age dementias in two multicenter, clinical trials. A total of 755 elderly patients suffering from mental deterioration of degenerative or vascular origin were enrolled in the studies. In the first study, 352 patients received nimodipine 30 mg TID orally for 3 months; in the second study, 403 patients received the same treatment for 6 months. In both studies, psychobehavioral instruments showed a highly significant improvement of the global functional state. In hypertensive patients, nimodipine had a synergistic effect with the antihypertensive drugs. These results confirm the therapeutic efficacy and safety of nimodipine in the treatment of old age dementias. PMID- 8519048 TI - Use of a prefilled insulin syringe (Novolin Prefilled) by patients with diabetes. AB - A study was conducted to assess patients' acceptance of a new insulin injection system, Novolin Prefilled, and to record their opinions about its use during a 4 week study period. Sixty-four patients, aged 20 to 69 years, with type I (n = 19) or type II (n = 45) diabetes mellitus entered and completed the study; 22 were new insulin users and 42 had been treated previously for 6 months to 43 years. Patients received insulin treatment via a prefilled syringe that was designed to provide a convenient alternative method for injecting insulin. The syringe is prefilled with 150 U of insulin and can deliver up to 58 U per dose. After 2 to 4 days of using the new system, patients reported no major problems when asked about mechanical difficulties, and the percentage reporting mild hypoglycemic events was comparable to baseline. During the 4-week study, no patients reported moderate or severe hypoglycemic episodes. The results of attitude questionnaires revealed that after treatment significantly more patients (P < 0.05) reported feeling energetic and full of pep, in good control, and not worried about giving themselves insulin injections. The increase in positive attitudes was most apparent among the patients new to insulin use. Most of the study patients (98%) reported that the prefilled syringe was convenient and easy to use, 95% found it took less time to use at home, and 91% wished to continue using it for insulin delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519049 TI - Formularies: the role of pharmacy-and-therapeutics (P&T) committees. AB - Pharmacy-and-therapeutics (P&T) committees have been established by most hospitals and serve as the primary formal communications link between pharmacy and the medical staff. The P&T committee is responsible for all matters related to the use of medications in the institution, including the development and maintenance of the formulary (the continually revised compilation of drug products available to the medical staff). The basic objectives of a P&T committee are to specify drugs of choice and alternatives, based on safety and efficacy; to minimize therapeutic redundancies; and to maximize cost-effectiveness. Procedures necessary to strengthen the role of P&T committees and improve their decision making processes are discussed. The increasing concern with controlling health care costs will support the continued expansion of P&T committees, formularies, and the formulary system. PMID- 8519050 TI - Regulation of biotechnology products in the global pharmaceutical market: the case of the European community and the United States. AB - Biotechnology represents an opportunity for innovative products, new markets, or capital investments, depending on one's perspective. A primary consideration in regulating this industry is to ensure that innovation is not stifled yet the public is protected from potentially unsafe or ineffective products. We compared the regulatory requirements and procedures for obtaining marketing approval for biotechnology products in the European Community (EC) and the United States and identified key concerns of the biotechnology industry regarding the regulatory aspects of these products. The methodology consisted of a secondary literature review and mail survey. Biotechnology products are approved faster in the EC than the US. Both the EC and the US use advisory or expert committees in their respective approval procedures, although the EC does so more regularly. Market exclusivity provisions for biotechnology products range from 6 to 10 years in the EC compared with 7 years for "orphan" biotechnology products in the US. Regulatory affairs managers of the biotechnology industry were most concerned about application review time periods, communication with regulatory agencies, consistency in implementing regulations, and public policy changes. These concerns provide insight into the deficiencies that exist in regulatory processes and are valuable in identifying problems and implementing improvements. PMID- 8519051 TI - Effectiveness of clinical pharmacist interventions in a hemodialysis unit. AB - Many patients with end-stage renal disease are treated with a complex pharmacotherapeutic regimen that requires constant and thorough monitoring. The role of a clinical pharmacist in contributing to the care of patients receiving long-term hemodialysis in an outpatient dialysis unit was assessed. Therapeutic interventions provided routinely by the clinical pharmacist were recorded and then categorized and evaluated by two independent clinical pharmacists with expertise in nephrology pharmacotherapeutics. Of the 205 interventions recorded, 97.6% were initiated by the clinical pharmacist and 91.7% were accepted by the medical team; 80.9% were judged to have primarily affected the quality of care. The purposes of interventions were drug selection in 32.2% of cases, drug discontinuation in 19.0%, dose selection in 24.4%, and therapeutic monitoring in 24.4%. Most interventions were initiated in response to abnormal laboratory test results. When the interventions were ranked according to clinical significance, 34.6% were involved with the preservation of major organ function and 62.4% with improvement of the quality of care to acceptable standards. Of all the interventions accepted by the medical team, 90.5% resulted in positive patient outcome; 7.9% resulted in no observable change or had no effect on outcome. The results demonstrate the potential influence and effectiveness of clinical pharmacy interventions on the drug therapy of patients receiving long-term hemodialysis. PMID- 8519052 TI - Lies and medicine: reflections on the etiology, pathology, and diagnosis of chronic lying. AB - The classification, etiology, ordinary pathology, and various medical and legal aspects of the phenomenon of lying are discussed. Five types of liars are identified: tellers of "white lies," pathological liars, professional liars ("confidence" men), spies, and patients with a psychosis or an organic brain syndrome. The characteristics of these types are analyzed, and methods of coping with them are outlined. PMID- 8519053 TI - The effect of a tannin-fluoride mixture on human dental enamel. AB - In this study, the effect of a tannin-fluoride mixture (Ta-F, 0.5% tannic acid, 450 ppm fluoride, pH 5.9) on dental enamel has been investigated by using scanning electron microscopy (SEM), electron probe microanalysis (EPMA) and X-ray diffraction (XRD), compared with the effect of acidulated phosphate fluoride (APF, 0.015 M phosphoric acid, 450 ppm fluoride, pH 5.3). Under the SEM, a large number of spherical globules (1-5 microns in diameter) were observed on the enamel surface treated with Ta-F. On a fractured cross section, these large globules showed a columnar appearance, measuring 2.5-5 microns each in height. They had a good range and formed a single coating layer on the enamel, whereas on the APF-treated enamel only very small spherical globules 0.1-0.5 micron in diameter were seen. Moreover, three types of connective patterns were observed between the basal ends of these columnar deposits and the enamel surface: (a) a pattern loosely attached to the enamel surface, (b) a pattern partially connected with the crystals of enamel, and (c) a pattern inserted into the pores of enamel. These columnar deposits also showed very strong resistance either to acid decalcification or to water washing. By EPMA and XRD examinations, a remarkable elevation of the fluoride profile accompanied by a high elevation of calcium was observed and CaF2 peaks were detected on the enamel surface. These results suggest that the columnar deposits might contain the CaF2-like substances and possess unique morphological and qualitative features which are quite different from the deposits found after APF or NaF treatment as described in previous studies. PMID- 8519054 TI - An in vitro study into the effect of a bacterial artificial caries system on the enamel adjacent to composite and amalgam restorations. AB - A microbial artificial caries system was used to produce caries-like lesions adjacent to amalgam and composite restorations. Polarised microscopy allowed measurement of outer and wall lesions depths. Comparison was made of the depths found in relation to the restorative materials, margin finishing procedures (composite group), varnish application (amalgam group) and thermal stressing. It was found that differences were detectable between the different restorative materials and the type of margin finishing procedure used in the composite group. Varnish application and thermal stressing had little effect. Some comparison is made between this microbial technique, other artificial caries techniques, and other methods of assessing marginal leakage. PMID- 8519055 TI - Accuracy and precision in vitro of Beetrode microelectrodes used for intraoral pH measurements. AB - The accuracy and precision of 12 different microelectrodes were assessed through a series of pH recordings of buffer solutions with known pH values. Some electrodes were quite accurate, yielding an average deviation of recordings from true values of about 0.05 pH units, while other electrodes yielded average deviations of up to 0.20 pH units. The precision of the electrodes also varied between electrodes. While all recordings were within 0.15 pH units from the true values for some electrodes, other electrodes showed a marked dispersion with less than 25% of the recordings being within 0.15 pH units from true values. For some electrodes accuracy depended on true pH values, while no such dependency was noted with respect to the precision of the electrodes tested. Both accuracy and precision may be impaired when pH recordings are made on solutions with pH values outside the pH range encompassed by the calibration buffers. Our results demonstrate that the accuracy and precision of these microelectrodes cannot be considered fixed and known parameters. Electrodes should therefore be checked prior to clinical use, and electrodes with low accuracy and precision should be excluded from further use. PMID- 8519056 TI - The effect of different concentrations of citrate in drinks on plaque pH. AB - The effect of 0.1, 0.2 and 0.4% citrate in 10% sucrose solutions on the plaque pH in vivo was tested in 20 volunteers using the plaque harvesting technique. Results showed that the pH response for the three test solutions with citrate was significantly less compared with that for 10% sucrose (positive control) alone (p < 0.05). Mean areas under the pH curve were: sorbitol (negative control) 0.02, citrate 0.2% 5.30, citrate 0.4% 6.24, citrate 0.1% 6.94 and 10% 12.69. The cariogenic potential index of all the citrate test drinks was almost half compared with a 10% sucrose solution (p < 0.05). It was concluded that the addition of relatively low levels of citrate in a sucrose solution reduces the acidogenic response in the plaque. PMID- 8519057 TI - Effects of a 12-month prophylactic programme on selected oral bacterial populations on root surfaces with active and inactive carious lesions. AB - In 15 caries-active patients, with a total of 770 exposed root surfaces, the effect of fluoride therapy and professional tooth cleaning was studied during a 1 year period. Dental plaque from 92 of the root surfaces and whole saliva samples were analysed at baseline and after 12 months for the presence of specific bacteria. The results showed that the number of active carious lesions had decreased from 99 to 46, while the inactive lesions had increased from 69 to 124. Of the active lesions which had been converted into inactive lesions, most were on the buccal and fewest were located on the distal surfaces. Lower plaque scores were found on sound and inactive root surfaces compared to active surfaces. The salivary concentrations of mutans streptococci and lactobacilli remained constant during the 12-month observation period. There was a tendency for higher levels of Streptococcus mutans in plaque from active lesions compared with sound root surfaces, whereas an inverse relationship was noted for the Streptococcus oralis group. No significant differences in the Actinomyces naeslundii counts were detected. In conclusion, the 12-month prophylactic programme had an effect on the clinical surface characteristics of root caries, but the components of the oral microflora selected for study seemed to be relatively unaffected during the observation period. PMID- 8519058 TI - Caries experience of 15-year-old children in The Netherlands after discontinuation of water fluoridation. AB - In 1973 the fluoridation of drinking water in the Dutch town of Tiel was discontinued. In order to monitor the effect of this measure, the caries experience in 15-year-old children was investigated annually from 1979 to 1988, both in Tiel and in Culemborg. In the latter town the drinking water had never been fluoridated. The caries data of 15-year-old children examined between 1968 and 1969 in Tiel (children having used fluoridated water from birth) and Culemborg were used as historical controls. In Tiel the mean number of DMFS increased between 1968/69 and 1979/80 from 10.8 to 12.7 (+18%) and decreased to 9.6 (-26%) in the following years; in 1987/88 the mean DMFS was 11% lower than in 1968/69. In Culemborg the mean DMFS score decreased between 1968/69 and 1987/88 from 27.7 to 7.7 (-72%). In 1968/69 the mean DMFS score in Tiel was 61% lower and in 1987/88 17% higher than in Culemborg. The question as to whether water fluoridation would have had an additional effect if it had been continued (presuming the application of existing preventive measures) cannot be answered, as there are no remaining communities with fluoridated water in The Netherlands. PMID- 8519059 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8519060 TI - Ratiometric confocal Ca(2+)-measurements with visible wavelength indicators in isolated cardiac myocytes. AB - We present a new method for ratiometric Ca2+ measurements using indicators with excitation spectra in the visible range of wavelengths. Laser-scanning confocal microscopy was used to record intracellular Ca(2+)-signals with high temporal and spatial resolution in single cardiac myocytes. The patch-clamp technique was applied to load the cells with the fluorescent Ca(2+)-indicators and to follow the membrane currents with the fluorescence signals simultaneously. Intracellular free Ca(2+)-concentration ([Ca2+]i) was estimated with a ratiometric method. An in vitro calibration procedure was used to convert the fluorescence ratio obtained with two different Ca(2+)-indicators (Fluo-3 and Fura-Red) into Ca(2+) concentrations. Fluo-3 showed an increase in fluorescence upon a rise in intracellular Ca(2+)-concentration, while the Fura-Red fluorescence decreased. Since the fluorescence of Fluo-3 was around 2-fold brighter than the Fura-Red signal the cells were loaded with a 1:2 mixture of the two indicators. The large increase of the fluorescence ratio during a rise in [Ca2+]i (up to 4-fold) allowed us to record time-resolved signals with this mixture even when monitored in a very small subcellular volume (around 1 micron3). Long lasting continuous recordings of the fluorescence were possible because the dye-mixture exhibited no detectable bleaching with illumination periods of up to 30 s. The use of the Fluo 3/Fura-Red ratio method should significantly facilitate and improve quantitative measurements of [Ca2+]i with high temporal and spatial resolution. Moreover, this approach is especially valuable when used with confocal microscopes which are usually equipped with lasers in the visible light range. Furthermore, it may be possible to use the same approach with mixtures of other indicators to estimate the concentration of other biologically important ions/compounds with a ratiometric calibration. PMID- 8519061 TI - Light-emitting properties of recombinant semi-synthetic aequorins and recombinant fluorescein-conjugated aequorin for measuring cellular calcium. AB - 15 kinds of recombinant semi-synthetic aequorins and a recombinant fluorescein conjugated aequorin were prepared and their properties in Ca(2+)-triggered luminescence were studied. The semi-synthetic aequorins showed a wide range of Ca(2+)-sensitivity. The luminescence intensity of a high-sensitivity type (hcp aequorin) was greater than 10(4)-times that of a low-sensitivity type (n aequorin) at pCa 6.0-6.5. The fluorescein-conjugated aequorin exhibited fluorescence in addition to the Ca(2+)-triggered luminescence, thus it can be used to visualize the diffusion and distribution of aequorin in cells. The data obtained, particularly the Ca(2+)-sensitivity curves, are useful in selecting a suitable semi-synthetic aequorin for an experiment. PMID- 8519062 TI - Activation of calcium entry by cyclopiazonic acid in thyroid FRTL-5 cells. AB - The aim of the present study was to investigate whether the Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA) could empty intracellular Ca2+ stores and activate Ca2+ influx in thyroid FRTL-5 cells. Addition of CPA to Fura-2 loaded cells rapidly increased intracellular free Ca2+ ([Ca2+]i) which then stabilized at a new elevated steady state level. The initial increase was mainly dependent on the release of sequestered Ca2+, but was decreased in Ca(2+)-free buffer and in depolarized cells. The plateau phase was totally dependent on extracellular Ca2+. Addition of Ca2+ to cells exposed to CPA in Ca(2+)-free buffer rapidly increased [Ca2+]i. This influx was decreased in depolarized cells and inhibited by SKF 96365. Addition of CPA to cells prior to stimulating the cells with ATP totally abolished the ATP-induced increase in [Ca2+]i. In Ca(2+)-free buffer, addition of ATP prior to CPA decreased the response in [Ca2+]i evoked by CPA. The results show that emptying intracellular Ca2+ stores with CPA rapidly activates influx of Ca2+ in FRTL-5 cells. Furthermore, ATP and CPA appear to release Ca2+, at least in part, from the same intracellular Ca2+ store in these cells. PMID- 8519063 TI - Microtubules, ribosomes, and RNA: evidence for cytoplasmic localization and translational regulation. PMID- 8519064 TI - Colchicine-induced stimulation of PMN motility related to cytoskeletal changes in actin, alpha-actinin, and myosin. AB - Colchicine-induced stimulation of polymorphonuclear leukocyte (PMN) locomotion is an interesting model because extension of blebs at the front occurs at a rate (about 2.4 microns/s) which is far above that reported for growth of actin filaments. The following cytoskeletal changes were observed in colchicine-treated PMNs: (1) a small increase in cytoskeleton-associated actin was noted, as well as a somewhat more pronounced increase in cytoskeleton-associated alpha-actinin, as compared with untreated or DMSO-treated controls. There was, however, no measurable increase in F-actin as determined by NBD-phallacidin binding; (2) the values for the ratio (alpha-actinin/actin) are lower in PMNs treated with colchicine for 30 min, as compared with PMNs stimulated with fNLPNTL for 1 minute (non-polar ruffling cells) or 30 min (polarized locomoting cells); thus, this ratio may depend on the type of PMN motility; (3) in polarized PMNs F-actin was mainly located linearly all along the cell membrane; there was more intense staining at the front of the cells; (4) alpha-actinin appeared to colocalize with F-actin at the leading front, but not with F-actin at the tail of polarized cells; (5) myosin was preferentially found at the rear part of polarized cells but not or only to a small extent at the front. Our data indicate a close functional correlation between microtubules and microfilaments. We speculate that F-actin in combination with alpha-actinin promotes expansion of pseudopods, whereas myosin combined with F-actin promotes contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519065 TI - Beta IV is the major beta-tubulin isotype in bovine cilia. AB - Four different isotypes of beta-tubulin are known to be expressed in mammalian brain. Monoclonal antibodies against beta II, beta III, and beta IV were used to characterize the beta-tubulin isotypes in two ciliated bovine tissues: non-motile sensory cilia of retinal rod cells and motile cilia of tracheal epithelium. Retinal rod outer segment (ROS) connecting cilia and cytoskeletons were purified by density gradient centrifugation. This preparation contained more than 20 major protein components, as shown by dodecyl sulfate polyacrylamide gel electrophoresis. Electroblots were used to quantitate the relative amounts of beta II, beta III, and beta IV. The connecting cilium and cytoskeleton of the rod outer segment has less type III beta-tubulin than brain and more type IV. The ratio of beta IV to beta II in the ROS is nearly a factor of 8 larger than in brain. Electron microscopic immunocytochemistry showed extensive labeling of cilia by anti-type IV in thin sections of retinas and trachea, and also in purified ROS cilia and cytoskeletons. Labeling of cilia by anti-beta II was also observed, although in the purified ROS cilia and cytoskeleton, the anti-beta II labeling was primarily on amorphous non-ciliary material. The results suggest that both motile and non-motile cilia are enriched in the type IV beta-tubulin subunit. PMID- 8519066 TI - Ultrastructure and immunocytochemistry of the isolated human erythrocyte membrane skeleton. AB - Isolated skeletons from human erythrocyte ghosts were studied using immunogold labeling; negative staining; and quick-freeze, deep-etch, rotary replication with Pt/C (QFDERR). Isolated skeletons visualized by QFDERR were similar to the negatively stained skeletons in that the proteins spectrin, actin, and ankyrin could be easily distinguished. However, the quick-frozen skeletons had two fewer filaments (4.2 +/- 0.7) at an actin junction. Immunogold labeling of skeletons with site-specific spectrin antibodies not only confirmed the designation of these filaments as spectrin molecules, but indicated that about 30% of spectrin filaments form non-actin junctions consistent with the hexameric organization of these filaments. Many of the filaments displayed a striking banding pattern indicative of underlying substructure. Isolated skeletons prepared by QFDERR also showed evidence of laterally associated spectrin filaments. These associations, as well as many hexamer junctions, are lost during negative staining. Negative staining also apparently caused approximately 21% of the spectrin filaments to separate into their monomeric subunits. These results indicate that the surface tension imposed during negative staining of isolated skeletons can cause a loss of interactions normally present in the intact membrane skeleton. PMID- 8519067 TI - Microtubule rearrangement and bending during assembly of large curved microtubule bundles in mouse cochlear epithelial cells. AB - Mature inner pillar cells in the mammalian organ of Corti are curved through about 60 degrees, where they arch over adjacent epithelial cells and the apex of an intercellular space called the tunnel of Corti. This report deals with changes in microtubule organization that are associated with cell bending and tunnel formation during morphogenesis of the mouse organ of Corti. A large bundle of up to 3,000 microtubules assembles in each inner pillar cell. Microtubule rearrangement occurs about 5 days after bundle assembly begins. The lumen of each initially straight hollow tube-shaped microtubule bundle is occluded as the bundle becomes more compact and elliptical in cross section. This event anticipates the once-only bending which subsequently occurs between particular levels (about 9-19 microns) below the top of a bundle as it curves into its final shape about 2 days later. Microtubule rearrangement presumably facilitates bending which is effected in the plane of least mechanical resistance parallel to the short axis of a bundle's elliptical cross-sectional profile. Precocious bending of bundles has been induced about 1.5 days in advance of the natural event. Abnormal positioning of these prematurely curved bundles indicates that bending is effected by a contractile mechanism located within bundles rather than being a response to externally applied forces. The potential importance of such microtubule-associated contractions for active modulation of the vibratory response in the cochlea during hearing is considered. PMID- 8519069 TI - Rheumatoid arthritis: classical rheumatoid lung disease. PMID- 8519068 TI - FRAP analysis of the stability of the microtubule population along the neurites of chick sensory neurons. AB - In order to study microtubule turnover in elongating neurites, chick embryo sensory neurons were microinjected with x-rhodamine tubulin, and after 6-12 hours, short segments along chosen neurites were photobleached at multiple sites. Previous studies [Lim et al., 1989; 1990] indicated that recovery of fluorescence (FRAP) in neurites occurs by the dynamic turnover of stationary microtubules. In all cases, distal bleached zones recovered fluorescence faster than bleached zones more proximally located along the same neurites. Bleached zones at growth cones completely recovered in 30-40 minutes, while bleached zones located more proximally usually recovered in 50-120 minutes. In the most proximal regions of long neurites, recovery of fluorescence was often incomplete, indicating that a significant fraction of the microtubules in these regions were very stable. These studies indicate that there are differences in microtubule stability along the length of growing neurites. These differences may arise from the combined effects of 1) modifications that stabilize and lengthen microtubules in maturing neurites and 2) the dynamic instability of the distally oriented microtubule plus ends. PMID- 8519070 TI - Juvenile rheumatic disorders. PMID- 8519071 TI - Muscle disorders and the lungs. PMID- 8519072 TI - Antirheumatic drug reactions in the lung. AB - Drug-induced lung disease during treatment with antirheumatic drugs should be considered in all patients receiving these agents who develop new pulmonary symptoms. When a potential drug-related reaction is identified, the possible offending agents should be discontinued, appropriate respiratory support initiated, and a thorough investigation for other causes of respiratory disease launched to exclude infection or other pulmonary processes. Lung biopsy may be needed to define the disorder completely. In patients with acute pneumonitis, the use of corticosteroids should be considered. Although significant morbidity and even mortality may occur with drug-induced pulmonary events, proper and prompt evaluation and treatment of these disorders can often result in complete resolution of the pulmonary disease. PMID- 8519073 TI - Rheumatoid arthritis: other rheumatoid lung problems. AB - In summary, it appears that factors such as smoking and the presence of secondary Sjogren's syndrome might be important in predisposing the rheumatoid patient to the development of lung disease. Genetic factors may moderate or magnify these risks. At a cellular level, specific macrophage colonies within the lung may interact with a subgroup of CD4 T lymphocytes to produce unopposed B-cell activation, leading to local IgM production and the formation of immune complexes. This can damage lung both directly by cytolysis and indirectly by granulocyte recruitment through the release of neutrophil chemotaxins. Early in the evolution of these processes, steroids appear able to reduce lymphocyte numbers and prevent lung damage occurring, presumably by immunological mechanisms, while later they may reduce granulocyte numbers and activity, halting further progression of lung disease in some patients, perhaps by a direct anti inflammatory effect. Confirmation of these mechanisms and the development of more specific therapeutic tools is probably dependent on studies which examine lung tissue directly by biopsy and may be aided by the application of more sensitive imaging techniques. PMID- 8519074 TI - Rare rheumatic disorders. A. Behcet's disease. AB - No more than 100 patients with respiratory involvement in Behcet's disease have been described in the literature. Haemoptysis, cough, dyspnoea and pleuritic chest pain are the main symptoms. Vasculitis and thrombosis of the great pulmonary vessels is the underlying condition in the majority of patients. Aneurysmal formation and rupture is possible and constitutes the most life threatening aspect of the disease. Behcet's syndrome should be considered in the differential diagnosis of haemoptysis and veno-occlusive disease, especially where large vessels are involved. Early detection and treatment is mandatory to save the patient's life. Other pleuropulmonary manifestations described, such as fibrosing alveolitis and pleural disease, occur less frequently in Behcet's disease, and carry a better prognosis. PMID- 8519075 TI - Rare rheumatic disorders. B. Relapsing polychondritis. PMID- 8519076 TI - Investigation of lung disease in rheumatic disorders. PMID- 8519077 TI - Systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is the most common of the connective tissue disorders and can involve virtually any organ in the body. It is associated with pleuropulmonary manifestations in well over 50% of cases. Pleuritis with or without pleural effusion is the most common manifestation and can be particularly troublesome to manage but is rarely life-threatening. More serious manifestations in the lung include acute lupus pneumonitis with or without alveolar haemorrhage, chronic lupus pneumonitis and pulmonary hypertension. These all contribute significantly to overall mortality in SLE. The association between SLE and the antiphospholipid syndrome, leading to venous thrombosis and pulmonary embolism, is well recognized. Up to 20% of all cases of SLE present in childhood and many of these have pulmonary features at presentation or during the course of their illness. Sepsis is one of the main causes of death in SLE and pulmonary sepsis in these often immunocompromised patients contributes a significant proportion. Several drugs can produce a clinical syndrome that has many of the clinical and immunological features of SLE. Pleuritis may be seen in up to half of these cases of drug induced SLE. The development of SLE and conditions such as sarcoidosis or asbestosis in the same patient may represent a simple coincidence but there is some evidence for a closer association between these disorders. PMID- 8519078 TI - Primary Sjogren's syndrome. AB - Significant abnormalities in pulmonary function are encountered in about 24% of patients with primary Sjogren's syndrome. The most common cause of dyspnoea is interstitial fibrosis, with a prevalence of around 8%, but a number of other pathologies may be encountered in the lungs of these patients (Table 1). Lymphoproliferative disorders are relatively uncommon, but these apparently benign lesions may harbour malignant potential. Interstitial fibrosis and the lymphoproliferative disorders may be responsive to corticosteroids or cytotoxic agents, and it is therefore important to establish an accurate diagnosis at an early stage. On the basis of our experience we would recommend the investigative strategy outlined below. Patients should be screened for significant lung disease by taking a careful history of respiratory symptoms followed by standard pulmonary function testing (including measurement of carbon monoxide diffusing capacity) and chest radiography. High resolution computed tomography is a non invasive technique that should prove superior to chest radiography in the detection of early cases of interstitial fibrosis. When the disease is patchy it may be useful in identifying areas of maximal involvement for subsequent biopsy. Bronchoalveolar lavage is a sensitive tool in the non-smoker, but lacks the specificity to command a significant role in the investigation of pulmonary pathology in these patients. One exception to this may be in the investigation of the clonality of lymphocytes which may allow early and specific diagnosis of lymphomatous proliferation. The application of techniques such as the polymerase chain reaction may assist in the investigation of the role of the Epstein-Barr virus in the causation of lymphoproliferative lesions. In most patients with significant symptoms and abnormalities of pulmonary function a tissue diagnosis will be required, either by transbronchial biopsy or by open lung biopsy. Both bronchial and interstitial lung tissue should be obtained where possible. Histological confirmation is probably mandatory when there is a recent history of parotid enlargement, weight loss or the appearance of a monoclonal gammopathy. Advances in our understanding of the mechanisms of the MALT system may provide the key to unlocking some of the mysteries of 'autoimmune' diseases such as Sjogren's syndrome. The response of lymphoproliferative disorders to immunosuppressive therapy provides hope that if the diagnosis of sicca syndrome can be made earlier lymphocyte induced tissue damage may be halted or reversed. PMID- 8519079 TI - Lung disease in systemic sclerosis (scleroderma). AB - Scleroderma (SSc) is a disease characterized by skin fibrosis but it is the end organ effect of microvascular injury and fibrosis that is important prognostically. Pulmonary involvement in SSc patients, either of parenchymal fibrosis and/or pulmonary hypertension, is a major cause of morbidity and mortality. Interstitial lung disease occurs more commonly in patients with diffuse SSc and is associated with a loss of lung volume, as well as a defect of gas exchange. Parenchymal fibrosis may also cause pulmonary hypertension. Isolated pulmonary hypertension occurs exclusively in patients with limited SSc and is detectable by a reduced DCO. The early identification of either manifestation is difficult. Patients may have minimal symptoms, unremarkable physical findings, normal chest radiographs and/or minimally abnormal pulmonary function tests at a time when significant lung pathology is present. It is essential to attempt to identify pulmonary disease early, at a potentially reversible stage. Multiple therapeutic endeavours have yielded only short-term or minimal benefits in symptoms and pulmonary function, and thus a major alteration in SSc pulmonary prognosis has not been achieved. Further study of the pathogenesis of this disease manifestation will be helpful in its earlier identification and intervention. PMID- 8519080 TI - Ankylosing spondylitis. AB - Ankylosing spondylitis is an inflammatory disease involving entheses and joints, especially those in and around the spine. The most widespread involvement of the respiratory system by this disease occurs when this pathological process gives rise to chest wall pain, diminished chest wall movement and a dorsal stoop. As healing of the inflammatory process takes place, calcification occurs which leads to rigidity of these structures, with consequent loss of chest expansion which is exacerbated by the increasingly kyphotic spinal posture and intercostal muscle inefficiency. Fortunately diaphragmatic function is unimpaired and compensates well, so that there are only minor restrictive changes found in tests of respiratory function. Treatment is by mobilizing physiotherapy coupled with a home exercise programme encouraging mobility and improved cardiovascular fitness. As with many physical treatment methods, good quality controlled studies of efficacy are rare. The role of medication is to ease symptoms and hence enable exercise. Apical fibrobullous lung disease is found in a small proportion of AS patients. The initial changes are mainly fibrotic, with bullae becoming more important as the condition progresses. The disease may progress to major cavitation, which is prone to infection, especially with aspergillae. No methods exist which can either prevent the development of fibrobullous disease or halt its progression, although this may happen spontaneously. The main effects of therapy are aimed at the diagnosis and treatment of superinfection. Treatment of established aspergillosis, especially when aspergilloma formation has taken place, is unsatisfactory and carries substantial risks of morbidity and death. Non-apical pleural involvement, including pleural effusion, is very rare. The most common cause of breathlessness in AS patients is cardiac involvement by the disease. PMID- 8519081 TI - Assessment of the reliability of school nurse height measurements in an inner city population. (The Hackney Growth Initiative). AB - To establish the reliability of school nurses given training in height measurement we conducted an intra- and inter-individual reliability study under field conditions. The measurements of 7 school nurses were compared with those of a trained auxologist. The pooled standard deviation of the differences between repeat measurements for the school nurses (0.32 cm) compared favourably with that of the auxologist (0.35 cm). Height measurements made by school nurses were accurate within the range of -0.53 cm to +0.64 cm when compared with the auxologist. We conclude that a single, accurate height measurement made by a school nurse would be sufficiently reliable for use in routine screening for short stature. PMID- 8519082 TI - Deleterious effects of the prone position in the full-term infant throughout the first year of life. AB - Seventy-one first-born infants who had been nursed in prone position since birth, were referred for motor assessment at 3 months, 5 months and 9 months. All infants were administered the same checklist of motor items, based on the Amiel Tison Infant Neurological Evaluation and on the Brunet-Lezine Developmental Psychomotor Scale. Abnormalities in muscular shortening and delay in motor skills were found. These findings are critical as regards environmental influences on postural development, continuities in motor development and issues of early primary prevention. Early identification and follow-up programmes, including frequent changes in posture, are suggested in order to avoid abnormalities of motor behaviour and subsequently in postural patterns. PMID- 8519083 TI - Liverpool Visual Assessment Team 1985-1989: 5 years on. AB - An update of the work of the Liverpool Visual Assessment Team. This is a multi disciplinary team for the assessment, remediation and management of severely visually impaired children in Liverpool and the surrounding region. PMID- 8519084 TI - Sleep management--the hidden agenda. AB - The management of apparent sleep problems is often not straight-forward because of a proportion of clients attending with a 'hidden agenda', requiring more in depth long-term treatment for psychological problems. This paper looks at a sample of 100 consecutive referrals to a community sleep clinic in the East End of London and attempts to address the question of who comes to the sleep clinic and why. A proportion of clients responded to brief intervention of a behavioural nature but 19% were referred on to other services for psycho-therapeutic help. PMID- 8519085 TI - Parents' views of community care for children with motor disabilities. AB - In this study we have ascertained the views of 40 parents of 4-year-old children with motor disabilities, on the health and education services, social service and the availability of respite care. The children with moderate or severe motor disability who were born in 1985, were identified from the Oxford Regional Register of Early Childhood Impairment. Thirty-three (83%) completed a questionnaire taken to the home by the health visitor. Although most parents had access to a range of services, lack of information in the early years, fragmentation of services and limited choices were identified as problems. Parents regarded the breadth of care provided by the pre-school teacher counsellor and the nursery school as very useful, whereas the health service and social services were perceived as less appropriate. This small study suggests that for some families, the objectives of community care as identified in the Griffiths Report (Griffiths 1988) and reiterated in the Children Act (1989) are not yet being met. PMID- 8519086 TI - An acute form of T gamma lymphoproliferative disease presenting with massive splenomegaly--importance of immunophenotyping for diagnosis. AB - We describe a case of T gamma lymphoproliferative disease (T gamma LPD) which presented in an uncustomary acute onset in an adult with massive splenomegaly. Morphologically the cells represented monocytic leukemia. Karyotyping and equivocol special stain results suggested hairy cell leukemia. Gene rearrangement indicated a T lymphocytic malignancy. Immunocytochemistry stains were not definitive. Immunophenotyping by flow cytometry defined the cells as consistent with T gamma LPD (CD45+, CD56+, CD2+, CD3+, CD11b+, and CD38+; some cells CD8+; and CD57-). Although the cells did not have spontaneous activity, which is often the situation for most cases of T gamma LPD, the cells could be partially induced with exogenous interleukin 2 to exhibit in vitro cytotoxicity against a natural killer lymphocyte-susceptible target cell line (K562) but not a lymphocyte activated killer target cell line (HEPG2). This report hopefully continues to increase the awareness of T gamma LPD as well as demonstrates an unusual acute form which could have been misdiagnosed unless a multidisciplinary approach, especially including flow cytometric immunophenotyping, was used to evaluate the patient. PMID- 8519087 TI - Suppression by HIV of IL-1 and IL-6 secretion in accessory cells: AC function defect partially corrected with exogenous IL-1 and IL-6. AB - To determine the effect of HIV infection on the accessory cell function of monocytes we measured the ability of HIV-infected monocytes to restore PHA induced and soluble anti-CD3-induced T cell blastogenesis. These T cells were highly purified and depleted of monocytes (< 0.5%) and activated T cells. Monocytes were isolated using gelatin-fibronectin-coated flasks (< 1% T cells) and after 4 days in culture with granulocyte/macrophage-colony stimulating factor, they were infected with HIV. Accessory cell (AC) function was tested 2 and 7 days later, employing autologous cryopreserved T lymphocytes. Monocytes infected with HIV for 2 days lacked the ability to permit phytohemagglutinin (PHA) and anti-CD3-induced T cell blastogenesis. Noninfected monocytes restored the proliferative response of purified T cells. Interleukin 1 (IL-1) and interleukin 6 (IL-6) levels in culture supernatants were low when compared to cultures with noninfected AC. Preincubation of monocytes with human anti-HIV neutralizing antibodies did not restore either of the responses. AC treated with heat-inactivated HIV had normal accessory cell function. The addition of IL-1 and/or IL-6 partially restored the AC function for PHA stimulation, but not for anti-CD3 stimulation. We conclude that HIV infection of monocytes suppressed their accessory cell function in the T cell blastogenesis assay. The response was partially restored with IL-1 and/or IL-6, suggesting that HIV infection down regulated the monocyte production of both cytokines. PMID- 8519088 TI - Regulation of synthesis of complement proteins in HEp2 cells. AB - We investigated the synthesis of complement proteins in HEp2 cells and its regulation. Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-PAGE, we demonstrated that HEp2 cells synthesized C1r, C1s, C1 inhibitor, C3, C4, factor B, and factor H. The constitutive synthesis of C1r and C1s were the highest among these proteins, whereas the synthesis of C4 was observed only when the cells were stimulated with IFN-gamma. C1r and C1s were secreted readily, whereas the rate of the secretion of C4 and C1 inhibitor was much slower. Activated forms of C1r, C1s, and complexes of C1 inhibitor--C1s were found. IL-1 and TNF induced 6- and 7-fold increases in the synthesis of C3 and factor B. IFN gamma induced increases in the synthesis of all seven proteins, the most pronounced effects being on the synthesis of C4 and C1 inhibitor--15- and 44 fold, respectively. PMID- 8519089 TI - Contact sensitivity in mice: differential effect of vitamin D3 derivative (calcipotriol) and corticosteroids. AB - Vitamin D3 derivatives are new compounds used topically for the treatment of psoriasis. To get better insights into the mechanisms of action of these compounds, we studied the effect of local treatment with calcipotriol (vitamin D3 synthetic analogue) and compared it to that of betamethasone dipropionate in a murine contact sensitivity (CS) test, the Mouse Ear Swelling Test. Two haptens were used: oxazolone and paraphenylenediamine. Betamethasone and calcipotriol exerted a differential effect on the delayed-type hypersensitivity response. When drugs were applied to the abdomen (sensitization site) before sensitization, no effect was observed. When betamethasone was applied to the abdomen for 4 consecutive days after epicutaneous sensitization, a diminution of the CS response to the relevant hapten was observed, whereas calcipotriol given in the same conditions did not affect the reaction. Ointments were then administered to the ear (elicitation site) either for 4 consecutive days prior to the challenge, or for 4 days before and 2 days after the challenge. In both conditions, calcipotriol and betamethasone exerted a differential effect on elicitation, the latter inhibiting and the former increasing the CS response to oxazolone and paraphenylenediamine. From these results we conclude: (1) that vitamin D3 derivatives are devoided of immunosuppressive effects when applied topically, and (2) that clinical improvement of chronic inflammatory dermatoses observed with topical vitamin D3 derivatives and corticosteroids is due to different mechanisms. PMID- 8519090 TI - HLA-DR alpha gene regulation in immortalized human thyroid cancer cells. AB - The induction of HLA class II antigens on human thyroid epithelial cells has been shown to be an intimate part of the pathology of autoimmune thyroid disease and may also be relevant to the natural history of thyroid neoplasia since thyroid cancer cells may show spontaneous HLA class II antigen expression. We have, therefore, analyzed the regulation of HLA-DR-alpha-specific mRNA transcripts, as a model for HLA class II antigen induction, in three established human thyroid cancer cell lines (papillary thyroid cell line NPA, and follicular thyroid cell lines RO-82-W1 and MRO-87-1). Each of the lines expressed 1.4 kb HLA-DR-alpha specific mRNA transcripts, either constitutively or after cytokine induction, but showed markedly different regulatory characteristics. For example, the induction of HLA-DR alpha mRNA in response to recombinant human interferon-gamma (IFN gamma) was inversely proportional to the degree of constitutive DR alpha mRNA expression; when there was constitutive absence there was a greater degree of induction. Similarly, the half-lives of the HLA-DR alpha mRNA transcripts varied from 80 to 420 min with the longest degradation time occurring in those cells lacking constitutive expression of HLA-DR alpha mRNA. These data indicated that the degradation rate was not a determinant of their constitutive expression. We also sequenced the 5' promoter region of the HLA-DR alpha gene (nucleotides -88 to -277 with respect to the translation start site) in each of the three cell lines. Sequence analyses revealed identity to the previously published normal human genomic sequence. Taken together, therefore, these data indicate that transactivating factors, rather than changes in mRNA degradation or promoter abnormalities, are the likely causes of variation in constitutive and cytokine induced HLA-DR alpha gene expression in human thyroid cancer cells. PMID- 8519091 TI - Antibodies to endothelial cells in patients with Behcet's disease. AB - Autoantibodies that bind to endothelial cells have been identified in patients with several forms of vasculitis. Behcet's disease--a multisystem inflammatory disorder of unknown etiology--is associated with thrombosis in addition to systemic manifestations resulting from small and large vessel vasculitis. We studied 72 Turkish patients (33 female, 39 male) with Behcet's disease in order to investigate the prevalence of antiendothelial cell antibodies (AECA) and to examine their possible relationship with clinical and laboratory features of the illness. Sera from 30 healthy Turkish people were used as controls. Human umbilical vein endothelial cells were cultured and used unfixed in a cellular ELISA to detect AECA. IgG and/or IgM AECA were found in 13 (18.1%) patients but not in healthy controls. Antiendothelial cell antibodies did not induce complement-mediated cytotoxicity as assessed by 51Cr release assay and the binding was not due to immune complexes. The prevalences of acute thrombotic events and retinal vasculitis at the time of the AECA assay among patients with AECA were significantly higher than those in patients without AECA. Laboratory parameters of active disease were higher in patients with AECA. There was no correlation between other clinical and laboratory features of Behcet's disease and AECA. Anticardiolipin and antineutrophil cytoplasmic antibodies were negative in our series, excluding a possibility of cross-reaction with AECA. Our results suggest a possible role of AECA in association with thrombosis and vasculitis in patients with Behcet's disease. PMID- 8519092 TI - Changes in cytokine production after measles virus vaccination: predominant production of IL-4 suggests induction of a Th2 response. AB - Immunization with live measles virus vaccine produces transient depression of delayed-type hypersensitivity (DTH) skin test responses and mitogen-induced lymphoproliferation irrespective of the serostatus of the recipient of the vaccine. To investigate this immune suppression further we studied peripheral blood mononuclear cells (PBMC) from adults before (N = 17) and at various times after (N = 34) immunization with measles virus vaccine. PHA-induced lymphoproliferation was decreased after vaccine and this was partly reversed by supplementation with rIL-2. There was no change in the proportion of PBMC that were CD4+ T cells, CD8+ T cells, NK cells, or B cells as analyzed by flow cytometry. Supernatant fluids were collected from PBMC after 72 hr in culture. Analysis for cytokines after vaccination showed spontaneous production of high levels of IL-4 (vaccinees 99 +/- 23; controls 5.6 +/- 5.6 ng/ml, P = 0.031) and TNF alpha (vaccinees 140 +/- 45; controls 42 +/- 14 pg/ml, P = 0.072) accompanied by low levels of IFN-gamma (vaccinees 1.3 +/- 0.6; controls 14.3 +/- 10.1 U/ml), IL-1 alpha (vaccinees 111 +/- 22; controls 442 +/- 107 pg/ml, P = 0.0001), and PGE2 (vaccinees 75 +/- 39; controls 300 +/- 72 pg/ml, P = 0.048). Increased amounts of IL-4 were also produced after stimulation with PHA (vaccinees 140 +/- 25; controls 40 +/- 40 ng/ml, P = 0.013) while levels of IFN-gamma and soluble IL 2 receptor were similar to controls and levels of IL-1 alpha (vaccinees 443 +/- 67; controls 792 +/- 118 pg/ml, P = 0.026) remained low. Addition of rIL-2 had little effect on these cytokine levels. These data suggest that Th2 cells producing IL-4 are preferentially activated by measures vaccine and may contribute to the immunologic abnormalities associated with immunization for measles and possibly other viral infections. PMID- 8519093 TI - Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism. AB - The role of microglia in host defense against Toxoplasma gondii is unknown. In the present study, we investigated the multiplication of T. gondii tachyzoites in murine microglial cell cultures. T. gondii multiplied readily in these cells; multiplication was prevented when microglia were activated with interferon-gamma plus lipopolysaccharide, a treatment that also upregulates nitric oxide (NO) synthase activity. Simultaneous treatment of microglial cell cultures with activation signals and the NO synthase inhibitor NG-monomethyl-L-arginine (NGMA) prevented the antitoxoplasmic activity. Transmission electron microscopic analysis demonstrated degenerative tachyzoites in activated microglia but not in control or NGMA groups. These findings support the view that the host defense function of activated microglia against T. gondii involves generation of the free radical NO. PMID- 8519094 TI - The use of the severe combined immunodeficient mouse and the athymic "nude" mouse as models for the study of human autoimmune thyroid disease. AB - The athymic "nude" mouse and the severe combined immunodeficient (SCID) mouse have differing immunological properties which permit complementary studies of autoimmune thyroid disease (AITD). The nude mouse accepts human thyroid xenografts, but lyses the passenger lymphocytes, whereas in the SCID mouse both the xenograft and its lymphocytes survive. Human AITD thyroid xenografts manifest a worsening of the pathological picture in the SCID mouse, but show a return to normal morphology and function in the nude mouse at the time of sacrifice 6-8 weeks after engraftment. Such tissue which has been grafted into the nude mouse can be retrieved and then can be re-xenografted into the SCID mouse. Normalized AITD thyroid tissue (from the nude mouse xenograft) will remain normal in the SCID mouse, but if xenografted into a SCID mouse which already has a primary autologous AITD thyroid xenograft, or if autologous PBMC are added, the AITD lesion will be reproduced. This demonstrates the primacy of the immune system in AITD and constitutes a useful model for the study of this human disorder. PMID- 8519095 TI - The operative treatment of fractures. 1947. PMID- 8519096 TI - External fixation of severely comminuted and open tibial pilon fractures. AB - Twenty patients with severely comminuted fractures about the ankle, either severely comminuted pilon fractures or open pilon fractures (three Grade II, seven Grade III), were managed with the use of a Delta-framed external fixator across the ankle joint. All fractures had open reduction and internal fixation (ORIF) with either screw fixation or small plates to stabilize the articular surface with minimal soft-tissue dissection. Average external fixator time was 2.5 months, and the time to union averaged 4.5 months. All fractures healed. Three delayed unions required bone grafting and two had plate stabilization. No infection occurred in the 12 open fractures. There was no infection of the closed injuries, no skin sloughs, and only two minor pin tract infections. Follow-up analysis averaged 12 months (range, six to 30 months). Range of motion (ROM) at last follow-up observation was excellent in six patients, good in nine, fair in three, and poor in two. Two patients required ankle arthrodesis because of posttraumatic arthritis. The ROM and outcomes of the severely comminuted or open fractures of the distal intraarticular tibia were very good. PMID- 8519097 TI - Open reduction and internal fixation of tibial plafond fractures. Variables contributing to poor results and complications. AB - In a retrospective study, 58 patients with 60 tibial plafond fractures were treated by internal fixation and reviewed over an average follow-up period of 2.5 years. There were three Reudi Type I, 27 Reudi Type II, and 30 Reudi Type III fractures. Twelve fractures were open, and 60% of the fractures were the result of high-energy trauma. Results were evaluated based on a subjective and objective rating system. There were 15 good and excellent (25%), 15 fair (25%), and 30 poor results (50%). The deep infection rate in Reudi Types I and II fractures was 0%, and in Type III fractures it was 37%. The deep infection rate statistically correlated with the presence of a postoperative wound dehiscence or skin slough but not with the presence of an open fracture. Overall clinical rating correlated with the Reudi classification, quality of reduction, and the presence of a postoperative wound infection. The ankle fusion rate for Reudi Types I and II fractures was 10%, whereas that in Reudi Type III fractures was 26%. The results of this study show that operative treatment of complex intraarticular fractures of the distal tibia remain fraught with difficulty and that the complication rates and need for further reconstructive surgery remains high. If anatomic reduction without soft-tissue complications cannot be predicted preoperatively, consideration should be given to alternative types of treatment. PMID- 8519098 TI - Open ankle fractures. The indications for immediate open reduction and internal fixation. AB - Twenty-two patients with open ankle fractures or fracture-dislocations were treated with irrigation and debridement, reduction, and immediate stable internal fixation at an average of six hours from initial evaluation. There were 13 women (59%) and nine men (41%), having an average follow-up period of 32 months (range, five to 111 months). There were six Grade I (27%), 15 Grade II (68%), and one Grade III (5%) injuries. Fractures also were classified according to the Danis Weber scheme (Type A [three cases]; Type B [eight]; Type C [11]). Excellent results were achieved in 14 patients (64%); good results in five (23%), and poor results in three (13%). There were four minor complications: two superficial would ulcerations, one loss of reduction requiring revision stabilization, and one distal tibiofibular synostosis. There were no deep infections or nonunions. Immediate debridement, irrigation, reduction, and internal fixation of open ankle fractures is clearly indicated in Grade I and clean Grade II open injuries. PMID- 8519099 TI - Extensive intraarticular fractures of the foot. Surgical management of calcaneal fractures. AB - Periodic cycles of enthusiasm for surgical management characterize the history of fractures of the calcaneus of the past century. After each period of advocacy for aggressive surgical therapy, there has been a trend toward nonoperative treatment. Morbidity and disappointing results were reported by those whose early attempts at open reduction were more difficult than expected. With the emergence of a subspecialty within orthopedic surgery devoted to fracture care, the pendulum has again swung toward operative treatment. A clearer understanding of fracture patterns from cross-sectional imaging, concentration of the injuries in the care of experienced fracture surgeons, perioperative antibiotics, rigid internal fixation, and early rehabilitation represent the latest attempts to improve the outcome from this vexing injury. Using an extensile lateral approach, rigid internal fixation, and early motion, more than 100 calcaneal fractures have been treated at the authors' institution between 1985 and 1989. Compared with published reports, the preliminary results demonstrate lower morbidity and improved outcome. PMID- 8519101 TI - Intraarticular fractures of the foot. Talus and lesser tarsals. AB - In the absence of historical comparative data for the treatment of tarsal fractures, commonly abided maxims of trauma care are noteworthy. A displaced fracture involving an articular surface or a fracture interrupting a mechanical axis is treated by open reduction and internal fixation. Rigid fixation is followed as early as possible with active and passive mobilization. Unlike long bones, whose motion and fracture patterns (i.e., segmental, transverse, and oblique) are understood, the tarsal bones are small bones with complex shapes and restricted motion. As a result, tarsal injuries most often occur with multiple ligamentous and bony injuries. Articular step-off is difficult to establish roentgenographically, the blood supply is tenuous, and fixation is largely dependent on screws and Kirschner wires. Good outcome can be obtained by following principles of internal fixation established in treatment of major joint injuries. PMID- 8519100 TI - Proximal humeral fractures. Management techniques and expected results. AB - During a ten-year period (1978-1988), 143 of 1386 patients with proximal humeral fractures were treated with internal osteosynthesis. Ninety-seven proximal humeral osteosynthesis cases had adequate documentation, and 77 (80%) were available for clinical review. The 97 fractures were graded by the AO/ASIF classification and included 44 Group A, 32 Group B, and 21 Group C fractures. Exercise-stable osteosynthesis using T-plate, cloverleaf plate, or small condylar plate was performed in 70% of patients. In the remaining patients, a less rigid fixation, with Kirschner wires or screws and cerclage wires, was used. Fifty-two percent of the patients had excellent and good results, 15% had fair results, and 33% had poor results. Most poor results occurred in patients with four-part fractures (61% of poor results). Of the cases involving four-part fractures, however, 22% had an excellent result after internal fixation. Displaced four-part fractures or fracture-dislocations should be treated by reconstruction of the proximal humerus, especially in young patients. The use of minimal fixation rather than rigid fixation is considered after careful assessment of the condition of the soft tissue and blood supply of the humeral head fragments. Primary treatment with endoprostheses is required when internal fixation is impractical in AO/ASIF fracture Types C 2/3 and C3 fractures. Improved clinical results may be achieved, particularly in the more severe fracture types, with increased experience in techniques of internal fixation of proximal humeral fractures. PMID- 8519102 TI - Pancreatitis after alar-transverse fusion for spondylolisthesis. A case report. AB - Acute pancreatitis complicated the postoperative care of a 16-year-old girl treated by alar-transverse fusion for spondylolisthesis. Pancreatitis was diagnosed by a marked increase in plasma amylase in conjunction with abdominal ultrasonography. Symptoms resolved with conservative treatment. Pancreatitis should be suspected when unusual abdominal symptoms persist after spinal surgery. PMID- 8519103 TI - The anterior cervical approach for traumatic injuries to the cervical spine in children. AB - In most cases of traumatic cervical spine injuries in children, nonoperative treatment, mainly external stabilization, is sufficient. When operative treatment is chosen, surgeons often recommend posterior stabilization. In a subset of pediatric patients, the anterior approach is indicated. The anterior operative approach was employed in six children three to 14 years of age who sustained trauma to the cervical spine. The injuries included severe hyperflexion injury with crush fracture and avulsion of the vertebral body, fracture-dislocation of the vertebral body with involvement of the posterior elements and the disk, and injuries that caused major anatomic deformity of the cervical spine with cord compression. Anterior decompression with bony fusion led to normal anatomic alignment with neurologic improvement in all patients. Follow-up evaluation as long as eight years showed solid fusion and remodeling of the bone grafts. The anterior approach should be used more frequently as the surgical procedure of choice in children with traumatic lesions of the cervical spine. The anterior approach provided direct visualization of the lesion, which enabled effective repair and stabilization, early ambulation with minimal morbidity, and significant long-term neurologic improvement. PMID- 8519104 TI - The influence of conformity and constraint on translational forces and frictional torque in total shoulder arthroplasty. AB - Glenoid loosening in total shoulder arthroplasty (TSA) may result from translational forces and frictional torque generated at the articular surfaces and transmitted to the fixation interface. The effect of glenohumeral articular design on the magnitude of these translational forces and frictional torques has not been evaluated previously. Seven different glenohumeral designs were evaluated on a specially designed fixture integrated with a materials test system. The degree of conformity and constraint in the glenohumeral designs directly affected the forces generated during translation and rotation of the humeral head. Maximum translational forces occurred close to the midline in the more conforming design. The less conforming designs generated lower translational forces and frictional torques. Because frictional torque and translational forces at the glenohumeral articulation may contribute to glenohumeral loosening, the use of less conforming and less constrained designs is advocated where possible to reduce the potential for mechanical loosening of the glenoid component. PMID- 8519105 TI - Atraumatic posterior dislocation of the sternoclavicular joint. A case report and literature review. AB - Atraumatic spontaneous posterior dislocation of the sternoclavicular joint (SCJ) is an extremely rare event. Only three recorded cases exist in the literature, and they are poorly documented and without roentgenographic confirmation. Spontaneous posterior dislocation of the SCJ occurred in an active 50-year-old woman without any known underlying pathology. Closed reduction attempted five days later was unsuccessful, and the patient was treated conservatively with short-term modification of activity. The patient is asymptomatic and followed carefully one year postdislocation. A review of the literature discloses a 25% complication rate involving the vital structures of the superior mediastinum after posterior dislocation of the SCJ. Because of this high complication rate, a thoracic or vascular surgeon must be available should closed or open reduction become necessary. PMID- 8519106 TI - Injuries of the ulnar collateral ligament of the thumb metacarpophalangeal joint. Biomechanical and prospective clinical studies on the usefulness of valgus stress testing. AB - In an effort to determine whether valgus stress testing of the thumb metacarpophalangeal joint is predictive of a torn and displaced ulnar collateral ligament, anatomic and prospective clinical studies were performed and the results correlated. In the anatomic study on autopsy specimens, dividing the proper collateral ligament resulted in a significant increase in valgus instability of the flexed metacarpophalangeal joint. Significantly less laxity was noted when the joint was tested in extension. When the accessory collateral ligament/palmar plate complex was also divided, valgus instability in extension increased to the extent that it no longer differed significantly from the values obtained when the joint was tested in 30 degrees flexion. In the clinical study, valgus instability of greater than 35 degrees when the joint was positioned in extension and then stressed consistently indicated the presence of tears of the proper and accessory collateral ligaments: A Stener's lesion was present in 15 of 17 such cases (87%). Values on valgus stress testing of the metacarpophalangeal joint in extension and 30 degrees flexion are highly predictive of both disruption and displacement of the ulnar collateral ligament of the thumb. PMID- 8519107 TI - Proximal interphalangeal joint arthrodesis using powered staple fixation. Observations on autopsy specimens. AB - A new method for internal fixation using power-driven staples was recently developed. In theory, this new technique should be ideal in performing small joint arthrodesis. In autopsy specimens, the biomechanical properties were observed in simulated proximal interphalangeal joint arthrodesis (PIP). The tension-band technique, acting as a control, was significantly superior. The two techniques had similar biomechanical properties. The three 7- x 7-mm staples is recommended. The tension-band technique remains the technique of choice in small joint arthrodesis. PMID- 8519108 TI - Roentgenographic densitometry of bone adjacent to a femoral prosthesis. AB - A digital imaging method was developed to quantitate the stress-related changes in roentgenographic bone density after total hip arthroplasty. A technique termed "histogram-directed equalization" was used to compensate for differences in postimaging data caused by the effects of variable quality obtained from ten patients. Quantitative change due to variation in delivered energy was decreased by 7% for roentgenograms obtained with a 2 kVp variation and 31% for roentgenograms obtained with a 4 kVp variation. The method allowed the authors to accurately describe the changes observed on annual postoperative roentgenograms obtained over the past decade. The utility of the method was demonstrated in 15 of the senior author's long-term cases treated with fully porous-coated implants. These cases were divided into two groups based on the diameter of the prosthetic stem implanted in each case. Five patients were grouped with small-diameter stems and ten with large-diameter stems. Both groups showed substantial decrease in roentgenographic bone density (from 11% to 28%) in the medial and lateral proximal regions. The large-diameter group had an overall larger decrease in roentgenographic bone density at two and five years. Roentgenographic bone remodeling changes were most pronounced in the first two years. Changes between two and five years progressed at a slower rate. The results also confirmed the predicted effect of stem diameter on bone remodeling patterns. PMID- 8519109 TI - Charnley low-friction arthroplasty of the hip. Long-term results. AB - Charnley low-friction arthroplasty (LFA) has become the method of choice for patients with destroyed arthritic hip joints; the authors' 18-26-year observation suggests that LFA could be considered the gold standard for total hip arthroplasty (THA). The continuity of concept, design, and the surgical technique extends beyond 29 years and offers predictability of outcome. Fatal postoperative pulmonary embolism, initially at 0.7% within one year of surgery, shows significant seasonal variation and as yet unexplained declining incidence. Incidence of dislocation is 0.63%, with a 0.11% chance of revision. The incidence of deep infection is 0.3%-1.5% in primary surgery and varies with the underlying hip pathology. Introduction of the intramedullary bone block has reduced the revision rate for stem loosening to less than 1% at 14 years and completely eliminated stem fracture. There has not been a fracture of a recently manufactured stem (Ortron). Revision for socket loosening has been reduced to 3% by the introduction of the ogee-flanged socket. The outcome of the socket survivorship is determined by the depth of socket penetration, the relationship between the two being exponential. Because the socket demarcation and migration are usually asymptomatic, the timing of revision would be determined by the surgeon's awareness of the problem. Repeated revisions produce conditions almost comparable to a locally malignant condition: dwindling bone stock, increasing implant size, local recurrence of the problem. Accumulation of the experience with the Charnley LFA has been shown to benefit both old and young patients. PMID- 8519110 TI - Insufficiency stress fractures of the femoral neck in elderly women. AB - Thirteen insufficiency stress fractures of the femoral neck in 13 elderly patients (average age, 82 years) were studied retrospectively. All occurred in Caucasian women with severe osteoporosis. A vague pain about the hip, of spontaneous onset, was the main symptom on first visit. The diagnosis was delayed in most cases because the clinical findings were minimal and the early roentgenographic features were absent or subtle. Bone scintigraphy was found more useful than roentgenography for diagnosing this entity. A completely displaced stress fracture of the femoral neck could not be distinguished clinically or roentgenographically from a traumatic subcapital femoral fracture. Internal fixation was the treatment method associated with the more favorable results. The histologic examination of removed femoral heads indicated that this entity is a dynamic metabolic process. Insufficiency stress fractures of the femoral neck in the elderly are not uncommon, but unless suspected, the condition can be easily overlooked, and if displaced, mistaken for trauma-induced subcapital femoral fractures. PMID- 8519111 TI - Prophylaxis with systematic antibiotics versus gentamicin bone cement in total hip arthroplasty. A ten-year survey of 1,688 hips. AB - In 1976, nine Swedish orthopedic departments started a prospective, randomized, and controlled study in which the prophylactic effect of systematic antibiotics (SAs) was compared with gentamicin bone cement (GBC) in 1,688 consecutive total hip arthroplasties (THAs). After ten years, 13 deep infections had occurred in the SA group and nine in the GBC group. The earlier reported significant difference at two and five years in favor of GBC no longer existed. No allergic or toxic reactions have been reported in the GBC group. PMID- 8519112 TI - Femoral neck fracture. Factors related to ambulation and prognosis. AB - A total of 427 elderly patients with femoral neck fractures were studied retrospectively to identify factors that may be correlated with life expectancy and functional prognosis. Gender, age, prefracture activities of daily living (ADL), electrocardiogram ECG), electroencephalogram (EEG), cognitive function, hemoglobin level, total protein level, and type of fracture were evaluated to determine the correlation of each predictive factor with survival time after surgery and three-month postoperative walking recovery rate. The one-year survival rate was found to be 55.9%: 59.1% for women and 52.3% for men. The walking recovery rate was 55.8%. The most important factors affecting life expectancy were prefracture ADL, ECG, EEG, and cognitive function score (Hasegawa's score). Electroencephalogram and Hasegawa's score also were found to be important prognostic factors for postoperative ADL. Preoperative medical conditions are useful indicators for determination of functional prognosis and survival. PMID- 8519113 TI - Parsons' knob (tuberculum intercondylare tertium). A guide to tibial anterior cruciate ligament insertion. AB - In some human autopsy specimens, a bony prominence located anterior to the tibial eminences represents the confluent insertion of the anterior horn medial meniscus and the medial fibers of the anterior cruciate ligament (ACL). The prominence has been called "Parsons' knob" by anatomists and the "tuberculum intercondylare tertium" by radiologists. This article reviews the anatomy and provides the first magnetic resonance image study and perhaps the first roentgenographic depiction of this landmark in the English-speaking orthopedic literature. This structure, if noted preoperatively, can be helpful in identifying the appropriate site of tibial tunnel placement for ACL reconstructive operations performed under arthroscopic or fluoroscopic guidance. PMID- 8519114 TI - Results of meniscectomy in the knee with anterior cruciate ligament deficiency. AB - Sixty-three knees in 62 patients with insufficiency of the anterior cruciate ligament (ACL) were treated by arthroscopic partial or total meniscectomy without ligament reconstruction. The implications of this sequence of treatment with this combination of pathologies was documented. At 4.5 years after meniscectomy, 84% of the knees were subjectively improved and 10% were subjectively worse. Sixty eight percent of the patients had persistent knee pain and 52% had episodes of giving way. Roentgenographic evidence of osteoarthrosis was present in 65% of 34 knees at 4.4 years after operation. Additional surgery was required in 24% of the knees. Meniscectomy without a stabilization procedure should be performed only infrequently in knees with deficient ACL. PMID- 8519115 TI - Achilles tenodesis for calcaneus deformity in the myelodysplastic child. AB - Calcaneus deformity in patients with neurologic disorders leads to gait disturbances, a high incidence of osteomyelitis, cellulitis, and skin breakdown, and a major problem in the fitting of shoes of orthoses. Correction of this deformity remains a difficult challenge for the orthopedic surgeon. Twelve tenodeses of the tendo Achillis to the fibula or tibia were performed in eight patients with myelodysplasia in an attempt to control calcaneus deformity. The average age of the patients at the time of surgery was 7.4 years (range, 3.1-13.5 years) with an average follow-up period of 6.3 years (range, two to 10.9 years). The clinical examination demonstrated definite improvement in the ability to brace, prevent skin breakdown, and improve gait in all but one patient who had progressive hindfoot valgus. Roentgenographically, there was improvement in the tibiocalcaneal angle in 67%, fibular station in 58%, talar tilt in 25%, and growth of the posterior aspect of the calcaneus in 58%. PMID- 8519116 TI - Survivorship of healed partial foot amputations in dysvascular patients. AB - The results of 94 initially successful, partial foot amputations in dysvascular patients were reviewed with survivorship analysis at a minimum of 6.5 years after surgery. Partial foot amputations were divided into three types: transmetatarsal amputations, metatarsophalangeal disarticulations, and ray resections. No amputation type was more or less likely to be treated with subsequent amputation of the foot or to develop recurrent ulceration. Taking all groups together, the chance of retaining the foot after an initially healed partial foot amputation was 86% at four years after operation and 76% at eight years after operation. Of these surviving feet, however, 53.8% developed ulceration or needed local reoperation. The chance of completely avoiding any surgery after an initially healed partial foot amputation was 71% at four years after operation and 52% at eight years after operation. In properly selected patients, partial foot amputations have significant longevity. PMID- 8519117 TI - Triple arthrodesis in rheumatoid arthritis. AB - Fifty-five patients with rheumatoid arthritis were treated with 65 triple arthrodeses of the hindfoot from March 1975 through July 1985. Twelve patients (12 procedures) have died, and follow-up evaluation could not be completed on three patients (four procedures), leaving 40 patients (49 procedures) available for clinical and roentgenographic evaluation. There were 32 women and eight men, with an average age at the time of surgery of 50 years. The follow-up period averaged five years. Standard operative technique involved medial and lateral incisions with staple fixation and local bone grafting. Correction of deformity was performed with closing wedge osteotomies. All patients had moderate to severe pain preoperatively and difficulty with ambulation. Postoperatively, 94% of the patients had significant pain relief and 83% had complete pain relief. Ambulatory status was improved in 80% of the patients. Ninety percent were at least community ambulators at the time of review, whereas more than half the patients were limited to household ambulation preoperatively. Complications included four superficial wound infections, all of which responded to local care. One patient required revision surgery for pseudarthrosis, and three patients had progression of ankle disease and required pantalar arthrodeses. There was no significant progression of fore-foot or knee symptoms, however, and there was no progression of ankle symptoms in patients whose hindfeet were corrected to 0 degrees-10 degrees valgus. Triple arthrodesis in the rheumatoid population has a high union rate. Pain relief and ambulation improvement can be expected. PMID- 8519118 TI - Intramedullary fixation of complicated fractures of the humeral shaft. AB - Since 1973, a specially designed intramedullary nail has been used for fixation of humeral shaft fractures complicated by malalignment, multiple trauma, metastatic disease, radial nerve palsy, or nonunion. A series of 22 consecutive patients with good to excellent results in 20 patients (91%) is reported. The humeral anatomy is reviewed to illustrate the method and the rationale for intramedullary fixation. This method is advocated over routine use of compression plate and screws because incision and surgical time are both minimal, and the fracture site is not exposed in primary cases unless there is radial nerve involvement. Closed reduction remains the preferred treatment for most fractures of the humeral shaft. PMID- 8519119 TI - Bicondylar intraarticular fractures of the distal humerus in adults. AB - Bicondylar intraarticular fractures of the distal humerus, because of their rarity and often associated significant displacement, comminution, and osteopenia, present the orthopedist with a difficult injury to reliably treat successfully. As with any displaced intraarticular fracture, the principles of anatomic restoration of the articular surface, stable fixation, and early motion are the optimal treatment goals. To obtain reproducible results, an established treatment protocol is required and is described in detail here. The average excellent-to-good results with surgical treatment for Type C fractures ("T" or "Y" bicondylar fractures) is 75% (range, 65-100%). Complications include heterotopic ossification (4%), infection (4%), ulnar nerve palsy (7%), failure of fixation (5%), and non-union (2%). PMID- 8519120 TI - Midtarsal fracture-subluxation. Case report and review of the literature. AB - Avulsion of the navicular tuberosity in association with fracture at the calcanecuboid joint is a characteristic pattern of injury resulting from an acute valgus and dorsiflexion stress. Only 22 cases of this unusual injury pattern have been reported, and confusion exists regarding treatment. Recommendations for management focus primarily on the calcaneocuboid disruption. Only two of these reports specifically addressed the posterior tibial tendon avulsion. Each component of this injury pattern should be considered separately. Calcaneocuboid fractures should be treated conservatively or operatively, depending on the extent of articular involvement. Conversely, the navicular tuberosity avulsion should be considered as the acute phase of a syndrome potentially leading to a chronic, posterior tibial tendon-deficient foot. Depending on the degree of displacement of the navicular avulsion fracture, prompt surgical intervention may be justified. A 73-year-old woman illustrates the rationale and treatment of a typical case. PMID- 8519121 TI - Segmental total knee arthroplasty after distal femoral resection for tumor. AB - Sixty-one patients treated with custom-made segmental total knee reconstruction after resection of a primary tumor of the distal femur were reviewed retrospectively. Two types of implants were used: the Walldius hinge prosthesis (Walldius Group, n = 45) and the Kinematic rotating hinge prosthesis (Kinematic Group, n = 16). The mean periods of follow-up observation were 6.4 years for the Walldius Group and 2.3 years for the Kinematic Group. The overall functional results in the Walldius Group were excellent in 7%, good in 26%, fair in 25%, and poor in 42% of the patients. Roentgenographic analyses showed that 50% of the patients had bony resorption, 33% had interface loosening, and 10% had prosthetic stems that were broken at the time of last follow-up evaluation. Forty-two complications occurred in 34 patients who needed additional surgical treatment. Nine of the prostheses in the Walldius Group failed (20%), and 27 of the complications (64%) associated with the use of the Walldius prosthesis occurred in the first three years after implantation. Nineteen Walldius prostheses (42%) were revised or removed for reasons other than local recurrence. The overall functional results of the Kinematic Group were as follows: excellent in 25%, good in 44%, fair in 25%, and poor in 6% of the patients. Roentgenographic analysis showed that there was no change in bone on 81% of the discharge roentgenograms, that there were no radiolucent lines in 87% of the prosthetic replacements, and that there were no radiolucent lines less than 2 mm thick on the roentgenograms. None of the Kinematic rotating hinge prostheses required revision, except one with a patellar button fracture, which was revised without compromising the functional results. Four complications occurred in three patients in the Kinematic Group, and two of them required surgical treatment. The patients with the Kinematic rotating hinge prosthesis had better early functional and roentgenographic results and fewer complications. PMID- 8519122 TI - Pigmented villonodular synovitis arising from the sheath of the extensor hallucis longus in an eight-month-old infant. AB - Pigmented villonodular synovitis (PVS) is a disease of unknown origin that most commonly affects the synovial joints and synovial sheaths of the skeletally mature. In an eight-month-old infant, a leg swelling thought likely to be a sarcoma proved to be PVS on biopsy. PMID- 8519123 TI - Baseball batting. An electromyographic study. AB - The muscle firing pattern in 12 muscles throughout the lower extremity, trunk, and upper extremity during the batting swing is described in this study. The two hamstring muscles studied and the gluteal muscle had a similar pattern of high muscle activity during pre-swing and early swing, and then rapidly diminished. The vastus medialis demonstrated peak activity between 95 and 110% maximum muscle test (MMT) throughout the swing phases and follow-through. The erector spinae demonstrated activity from 85 to 185% MMT during the swing phases. The abdominal obliques showed greater than 100% MMT during the swing phases and follow-through. The supraspinatus and serratus anterior showed relatively low muscle activity (less than 40% MMT). These results show that batting is a sequence of coordinated muscle activity, beginning with the hip, followed by the trunk, and terminating with the arms. Power in the swing is initiated in the hip, and therefore exercises that emphasize such strength development are indicated. The maintained, high muscle activity in the trunk muscles indicates a need for back and abdominal stabilization and rotation exercises. The relatively low level of activity in the four scapulohumeral muscles tested indicated that emphasis should be placed on the trunk and hip muscles for a batter's strengthening program. PMID- 8519124 TI - Fat embolism, intravascular coagulation, and osteonecrosis. AB - A triad of intraosseous fat embolism, intravascular coagulation (both thrombosis and hemorrhage), and osteonecrosis was pathologically demonstrated to coexist for the first time in humans. Specimens were evaluated from the earliest nontraumatic (18 hours) and traumatic (29 hours) femoral head lesions yet reported, and the cause and early pathogenesis were confirmed in a third case. An absolute overload of subchondral fat emboli, with hypercoagulability, stasis, and endothelial damage by free fatty acids, appears to cause end-organ death by triggering intravascular coagulation. This intermediary pathway appears to be capable of producing osteonecrosis by progressive fibrin platelet thromboses, which begin in vulnerable subchondral capillaries and sinusoids, especially when associated with arteriolar vasoconstriction and impaired secondary fibrinolysis (reperfusion of necrotic vessels with peripheral marrow hemorrhages). A relative overload of subperiosteal and subchondral fat emboli, which is below the ischemic/anoxic threshold but insufficient for intravascular coagulation, may cause osteopenia. PMID- 8519125 TI - Scarred muscle excision for the treatment of established ischemic contracture of the lower extremity. AB - Nine patients with rigid equinocavovarus contractures of the foot and ankle after ischemic episodes of the leg were treated from 1986 to 1989. The ischemic contractures occurred after tibial and fibular fractures in six cases, and after a trimalleolar ankle fracture, an electrical burn, and cardiac bypass surgery in one case each. Previous tendon and nerve releases had failed. The scarred portion of the various involved muscles of the deep posterior compartment were widely excised along with the respective tendons. A variety of additional foot procedures were generally necessary to obtain a plantigrade foot. Night splinting to maintain a plantigrade foot was prescribed for all patients. PMID- 8519126 TI - The management of the soft tissues in pilon fractures. AB - Fourteen patients with 15 pilon fractures were reviewed retrospectively to analyze cases treated by open reduction and internal fixation through both anteromedial and lateral incisions. The protocol for this procedure involved objective soft-tissue evaluation, anteromedial wound closure, judicious use of primary skin grafting, and delayed primary or secondary closure for the lateral wound. Eleven fractures were treated according to the established principles of the Association for the Study on Internal Fixation (AO/ASIF). The type and incidence of wound complications were recorded. Most injuries reviewed were of the high-energy or Type III fracture as defined by Reudi and Allgower. There was only one patient with a wound complication. This technique minimized the potential for wound complication and disastrous disability. PMID- 8519127 TI - Cell differentiation in response to partially purified osteosarcoma-derived bone morphogenetic protein in vivo and in vitro. AB - Bone morphogenetic protein (BMP) and associated noncollagenous proteins (NCP) were isolated from human osteosarcoma tissue. Implantation of 5- and 10-mg samples induced heterotopic ossification in the mouse quadriceps. Osteosarcoma derived BMP/NCP induced the same process of osteogenesis as human BMP/NCP isolated from bone matrix in vivo. In vitro continuous perfusion of neonatal rat muscle tissue with 5 micrograms/ml osteosarcoma-derived BMP/NCP increased glycosaminoglycan (GAG) synthesis significantly whereas DNA synthesis was relatively unchanged. Similar results were found when muscle tissue was preincubated with 200 micrograms of osteosarcoma-derived BMP/NCP for four hours followed by an incubation period of 14 days in BMP-free medium: GAG synthesis increased significantly, whereas DNA synthesis did not change. The increase in GAG synthesis coincided with cell differentiation but not cell proliferation. Histologic findings confirmed chondrogenesis in vitro. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that osteosarcoma derived BMP/NCP included a prominent component with a molecular weight of 18,000 d. PMID- 8519128 TI - Purification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type). AB - A protein fraction capable of eliciting cartilage or bone formation in vivo was purified more than 100,000-fold from a murine osteosarcoma (Dunn type). Intramuscular implantation of as little as 20 ng of the purified protein with 2 mg of pure skin collagen consistently induced ectopic new bone formation. The apparent molecular size of the purified protein was 32 kd on sodium dodecylsulfate-polyacrylamide gel electrophoresis. On reduction, the 32-kd protein split into subunits with the same partial amino acid sequences, and these partial sequences were identical to those of human bone morphogenetic protein-2B (BMP-4) which is assumed to be a member of the transforming growth factor-beta superfamily. PMID- 8519129 TI - Collagen and alkaline phosphatase gene expression during bone morphogenetic protein (BMP)-induced cartilage and bone differentiation. AB - Endochondral bone formation induced by bone morphogenetic protein (BMP) involves expression of collagen Types I and II and alkaline phosphatase (ALP) genes. Expression of these genes was studied in mice after implantation of BMP. The amount of Type I collagen mRNA increased from Day 3 to Day 7, when mesenchymal cell aggregation was observed. On Day 17, Type I collagen mRNA expression was correlated with an increased number of osteoblasts. Type II collagen mRNA increased from Day 7 and coincided with chondroblast appearance. This increase was suppressed by Day 17, although hypertrophic and degenerative chondrocytes were present. Alkaline phosphatase mRNA increased markedly from Day 7 with the appearance of chondroblasts. The high level of ALP mRNA continued until Day 11, during chondrogenesis. Mineral deposition was first observed roentgenographically on Day 11. Thus, BMP-induced bone formation occurs with the expression of collagen Types I and II and ALP genes. PMID- 8519130 TI - Studies of allotransplantation of bone using immunohistochemistry and radioimmunoassay in rats. AB - Immunohistochemistry and radioimmunoassay were used to study the rejection mechanism of allografted bone tissue in rats through changes in major histocompatibility complex (MHC) antigen expression by osteocytes in the allograft and in alloantibody levels in the serum of the host rats. Some osteocytes in normal rat bone tissue expressed MHC Class I antigen, and the degree of expression varied among the osteocytes. The expression of MHC Class I antigens on osteocytes of allografted bone tissue increased with time after allograft transplantation. When DA strain bone tissue was allografted to F344 strain host tissue, a marked decrease in the number of osteocytes was observed, and almost all of the remaining osteocytes strongly expressed MHC Class I antigens in the allografted bone tissue three weeks after transplantation. F344 strain rat recipients with DA strain rat bone grafts showed high titers of anti Class I alloantibody. These titers increased two weeks after transplantation. Major histocompatibility complex Class I antigens on osteocytes may play an important role in allograft rejection, as has been observed in other transplanted organs in the rat. PMID- 8519131 TI - The synovial response to intraarticular injection in rats of polyethylene wear particles. AB - To study the effect on tissues of wear particles commonly released from the articulating surfaces of joint prostheses, ultra-high-molecular-weight polyethylene particles were prepared in a joint simulator and injected into rat knees. The particles caused synovial proliferation and induced a macrophage and multinucleate giant-cell response in the subsynovium. Of particular interest was the macrophage response to particles ranging from 5 microns in maximum dimension to the limits of resolution of the light microscope; the multinucleate giant-cell response occurred in response to larger particles and aggregates of small particles. These findings emphasize the importance of wear particles in causing an adverse tissue response around joint replacements having a polyethylene component. The difference in cellular response to wear particles of different size suggests that not only the prosthesis material but also the pattern of wear and size of wear particles produced at the articulating surfaces of a prosthesis will determine the type of cellular response. PMID- 8519132 TI - Microvascular and cellular defects of the periosteum of osteogenesis imperfecta. AB - Periosteum stripped from fragments of diaphyseal long bones from osteogenesis imperfecta (OI) patients was examined both in vivo and in vitro. The OI periosteum was thickened and characteristic finding was a defective microvascular system. The vascular walls of arterioles and capillaries were thick and the lumina of many of these vessels were narrowed or occluded by hypertrophic endothelial cells and multiplication of smooth muscle cell layers. Circulatory deficiency in the OI periosteum might be regarded as one of the causes of the slender, osteopenic diaphyseal bone characteristic of the disorder. A higher proliferative activity was observed in cultured OI periosteal cells, but the cytoplasmic structure showed increased myelinoid bodies and smooth endoplasmic reticulum and decreased lysosomes and rough endoplasmic reticulum. These findings may be related to the abnormal metabolic activity of OI periosteal cells. PMID- 8519133 TI - The effect of methylprednisolone on porcine bone morphogenetic protein in fracture healing. An experimental allograft model in rabbits. AB - Four different experiments were performed to study the effect of methylprednisolone on porcine bone morphogenetic protein (pBMP) in an allograft in adult rabbits. In each animal, a 2-cm segment of radius was excised and replaced with frozen allograft. Fifteen milligrams pBMP was applied over the graft-host junction in Groups I and III, and 30 mg pBMP was applied in Groups II and IV. In Groups III and IV, methylprednisolone was given intramuscularly for three weeks. Incorporation was assessed by roentgenography, analysis of the area of callus formation and histologic and biomechanical analysis at four and eight weeks. Methylprednisolone inhibited pBMP-induced bone formation and incorporation of frozen cortical bone allograft. PMID- 8519134 TI - Comminuted fractures of the proximal radius and ulna. AB - Forty-three comminuted fractures of the proximal radius and ulna in 34 patients were treated with operative stabilization using AO/ASIF techniques. The patients were divided into three groups, according to the type of injury: Group I, isolated comminuted fractures of the olecranon (18 patients); Group II, isolated fractures of the radial head (eight patients); Group III, combined olecranon and radial head fractures (eight patients). All fractures were followed until union. The average follow-up period was 18 months (range, 12-48 months). At the time of this review, the average limits of elbow motion were 20 degrees extension, 118 degrees flexion, 65 degrees pronation, and 62 degrees supination. Two patients were unable to return for follow-up examination. Using the functional classification of Broberg and Morrey, results were rated as excellent in nine cases, good in 15, fair in five, and poor in three. The complication rate in this series was 19%: Two patients developed nonunion, and one patient lost reduction during rehabilitation. All of these patients required reoperation, with eventual satisfactory outcome. Three patients developed heterotopic ossification, two of which were minor and one of which produced ankylosis of the elbow joint. Each of these patients had delayed (more than 72 hours postinjury) stabilization. A functional elbow was achieved in 29 of the 32 patients who returned for follow-up examination. Operative stabilization of comminuted fractures of the proximal radius and ulna provides a stable painless joint with a functional, but not full, range of motion. PMID- 8519135 TI - The effect of axial and torsional loading on strain distribution in the proximal femur as related to cementless total hip arthroplasty. AB - This study investigated the normal load transfer pattern in the intact proximal femur. Both longitudinal and circumferential strains at eight strain-gauge locations were measured in response to both axial loads (1,000 and 2,000 N) and torsional loads (10 and 20 N . m). Under axial loads, strain magnitudes were large in the proximal regions and decreased distally. Very high compressive longitudinal strain was generated at the surfaces of the proximal medial cortical region, yet circumferential strain at this region was relatively low. Singh osteoporosis classification and femoral head diameter significantly affected the strains in the proximal part of the femur, and femoral head offset significantly affected strain levels in the diaphysis. Under torsional loads, the magnitudes of strain were much smaller than those generated under axial loads, but they increased distally. This study suggests that the proximal part of the femur is equipped for high longitudinal strain but is not equipped to handle high circumferential strain. The diaphysis of the femur is exposed to both axial and torsional loads and is equipped to handle high longitudinal and circumferential strains. Femoral implants that generate high circumferential strain in the proximal femur and high bending stress in the diaphysis are likely to fail mechanically or cause significant bone remodeling. Femoral implants and surgical procedures should be designed to apply load to the femur in a manner in which the femur can handle it best. PMID- 8519136 TI - Detection of HIV in bone allografts prepared from AIDS autopsy tissue. AB - Processed bone from an AIDS patient was tested for the presence of the human immunodeficiency virus type 1 (HIV-1). The preliminary procedures used to process bone allografts included removal of adventitious material and two cycles of freeze thawing. Although infectious virus was readily observed in plasma and bone marrow cells taken at autopsy, no infectious virus was detected in processed bone fragments. However, by using the polymerase chain reaction procedure, the presence of proviral HIV DNA could be demonstrated in processed bone allografts from this donor. Whereas the best safeguard against transmission of HIV by allografts is rigorous criteria for the exclusion of seropositive individuals as donors, proper procedures for processing bone allografts can further reduce the possibility of HIV transmission by bone allografts in cases where tissue from an infected donor is collected and processed. PMID- 8519137 TI - The operative treatment of intraarticular fractures of the distal radius. AB - Surgical management of 13 complex intraarticular (pilon) fractures of the distal radius was remarkably effective. Most of the fractures were the result of high energy impact, with associated soft-tissue trauma in seven cases. The preoperative planning, fracture classification, surgical tactics, and results are presented in detail. Only three patients had any residual functional problems. Follow-up motion showed wrist dorsiflexion/palmar flexion to be 74% of the opposite side, and grip strength was 76% of the opposite side. Twelve of the 13 patients showed no roentgenographic evidence of posttraumatic arthritis at an average follow-up period of 2.5 years. PMID- 8519138 TI - The treatment of acetabular fractures through the ilioinguinal approach. AB - The ilioinguinal approach was developed in 1965 as an anterior approach to the pelvis and acetabulum. Before this date, the Smith-Petersen incision or a modification of it called the iliofemoral approach provided the only access to the upper part of the anterior column of the acetabulum. In the current study of 195 acetabular fractures, the ilioinguinal approach was used alone in 178 cases (90%) and in combination with the Kocker-Langenbeck as a double incision in 17 cases (10%). There were 39 simple and 156 complex associated fracture patterns. There were two large groups of associated fractures: anterior column posterior hemitransverse (39 fractures) and both column fractures (98 cases). Of these fracture patterns stabilized through the ilioinguinal approach, there was a rate of perfect reduction of 85% and 73%, respectively. Of 70 fractures involving the anterior column, anterior wall, and anterior column posterior hemitransverse, there were 61 perfect reductions (87%). The complication rate was extremely low, without any evidence of external iliac fossa heterotopic ossification. The ilioinguinal approach provides total and complete access to the anterior column from the sacroiliac joint to the pubic symphysis. An experienced acetabular surgeon may achieve excellent results even with complex fracture patterns. PMID- 8519139 TI - The treatment of fractures of the femoral neck. AB - Fifty-four femoral neck fractures in young adults (20-50 years old; Group I) were compared with 397 fractures in the elderly population (older than 60 years of age; Group III). Patients in Group I were more frequently men and had often sustained vertical shear fractures in high-energy injuries. Treatment consisted mostly of open reduction and internal fixation (88%). There were no infections, pulmonary embolisms, or deaths. The rate of avascular necrosis was 10%; the rate of delayed union or nonunion, 17%; and the revision rate, 20%. Reoperation did not preclude an excellent final outcome. Patients in Group III were mostly women who fell at home and sustained an adduction fracture, which was most frequently (80%) treated with a cemented monopolar arthroplasty. Complications included pulmonary embolisms (3.5%), other cardiovascular complications (8%), and respiratory complications (7%). The death rate during hospitalization was 6.5%; for the first year after surgery it was 21%. These complications were not more frequent with either hemiarthroplasty or internal fixation. Local complications required revision of 17% of the cases treated with internal fixation and 1.4% of the patients treated with hemiarthroplasty. In the entire series, the deep infection rate without prophylactic antibiotics was 1.5%; with prophylactic systemic antibiotics it was 0.7%. The incidence of pulmonary embolism without thromboprophylaxis was 3.2%; with fixed-dose, subcutaneous heparin it was 1.1%. Of those treatments tested, open reduction and internal fixation with cancellous bone screws (for the younger patients) and hemiarthroplasty (for the elderly patients) yield the best short-to-midterm results. In addition, thromboprophylaxis with fixed-dose subcutaneous heparin and systemic antibiotic prophylaxis will continue to be used. PMID- 8519140 TI - Management of articular fractures. PMID- 8519141 TI - Tibial plateau fractures. Management and expected results. AB - The objective of treatment of tibial plateau fractures is precise reconstruction of the articular surfaces, stable fragment fixation allowing early motion, and repair of all concomitant lesions. A classification scheme is employed to include the high incidence of concomitant lesions in specific fracture types. The term "complex trauma" is used for extensive injuries involving multiple structural elements of the knee joint. Exact grading of the soft-tissue injury is crucial for the treatment plan. The authors suggest a four-grade classification system of closed and open soft-tissue injury. Preferred treatment is open reduction and internal fixation (ORIF) in all displaced and unstable tibial plateau fractures. A stepwise approach is used in complex knee trauma. Primary treatment includes closed reduction, wound debridement, if necessary, and external fixation of the femur and lower leg ("transfixation"). Open reduction and internal fixation and complex bone and soft-tissue reconstructions are performed in a second operation after recovery of the soft tissues. A follow-up study of 190 of 244 cases of tibial plateau fractures treated in the authors' institution from 1981 to 1987 showed good results after operative treatment, even in extensive fractures, with a tolerable complication rate. The functional recovery was relatively impaired in multiple injured patients and in complex knee trauma. PMID- 8519142 TI - The staging of pancreatic adenocarcinoma. PMID- 8519143 TI - The role of angiography in the investigation of acute or chronic gastrointestinal haemorrhage. AB - We have reviewed the clinical details and radiology of all patients with non variceal gastrointestinal haemorrhage referred for angiography during an 8 year period. Forty-six patients with a history of overt bleeding had 49 technically satisfactory angiograms of which 29 were true positives but 16 were false negatives (sensitivity 64%, accuracy 63%). The accuracy of angiography in this group was much higher (92%) in those patients referred within 24 h of admission. Nine patients who had a history of iron-deficiency anaemia due to sub-acute blood loss had 9 angiograms. Five studies in this group were correct (two true negatives and three true positives) but there were four false positive studies. Angiography is an effective means of diagnosis in patients with acute gastrointestinal haemorrhage who have a negative endoscopy but best results will only be achieved when the study is performed with minimal delay following negative endoscopy. Angiography should also be considered in patients with continuing subacute blood loss when other investigations are negative. PMID- 8519144 TI - The facial profile in the diagnosis of fetal abnormalities. AB - In order to assess the significance of fetal facial anomalies detected by ultrasound, a 4 year review was made of all detailed antenatal scans performed in our department. Anomalies were detected in 24 fetuses. All findings were subsequently confirmed. Micrognathia was the most common finding, 38% of these had an abnormal karyotype, and 45% had a recognized skeletal dysplasia. Facial clefting was also commonly seen, both in isolation and associated with other abnormalities. When associated with other abnormalities, 40% of cases with facial clefting had a chromosomal abnormality indicating a need for karyotype analysis in these patients. Other anomalies detected included cebocephaly, hypotelorism, frontal bossing, exophthalmos and hypertelorism. We feel that visualization of the fetal face is an essential part of the assessment of intracranial abnormalities and is valuable in any situation where a chromosomal abnormality or a skeletal dysplasia is suspected. PMID- 8519145 TI - Ultrasound anatomy of the left gastric vein. AB - A study of 187 consecutive patients undergoing upper abdominal ultrasound was conducted to evaluate the size and the ending of the left gastric vein (LGV) into the portal system and its relation to the coeliac axis and tributaries. The LGV was identified in 86 (46%) of these patients; the mean size of the LGV was 2.4 mm, 30% terminating in the portal vein, 33% at the splenoportal junction and 37% in the splenic vein. The LGV was anterior to the coeliac trunk and its branches in 45%, two thirds of these ending in the splenic vein and posterior in 51% of the cases, 86.3% of which ended at or to the right of the splenoportal junction. In conclusion, the variation in the site of termination of the LGV has a significant correlation with the course of the LGV in relation to the adjacent vessels. The LGV tends to cross superficial to the splenic artery when it enters the splenic vein and deep to the common hepatic artery when draining in the portal vein. PMID- 8519146 TI - Colour flow mapping in the diagnosis of the calf deep vein thrombosis. AB - This prospective trial was organized to evaluate further the role of colour flow Doppler ultrasound techniques in the diagnosis of deep vein thrombosis (DVT) with particular reference to the isolated calf lesion. In 100 patients ultrasound was compared against the recognized gold standard of ascending venography. Fifty venograms were positive for DVT compared with 49 on ultrasound, a sensitivity of 98%. The specificity of ultrasound for DVT in the 50 patients without DVT on venography was 100%. Forty-five venograms demonstrated calf thrombus with varying proximal extent. Sixteen proved to be isolated calf lesions and these were all identified by ultrasound (100% sensitivity and specificity respectively for isolated calf DVT). In five of these isolated calf thrombus cases, results suggested that ultrasound better diagnosed the presence of thrombus. Ultrasound diagnosed significant pathology in 13 of the normal venogram patients giving an overall diagnostic yield of 62% as compared to 50% at venography. PMID- 8519147 TI - CT cisternography in the investigation of cerebrospinal fluid rhinorrhoea. AB - Eighteen consecutive patients with cerebrospinal fluid (CSF) rhinorrhoea investigated by computed tomographic cisternography (CTC) are reported and the literature is reviewed. Twenty-one CTC studies were performed without complications on nine patients presenting with spontaneous CSF rhinorrhoea, six with head injury and three who had undergone craniotomy. Two meningoceles and two encephaloceles were found in patients with spontaneous rhinorrhoea. The site of the CSF leak was identified in 17 examinations (81%) and verified at operation in 14 patients--no surgery was performed following two examinations--and in one the site of leakage was not identified at operation. No defect was identified in three (14.3%) examinations and in one the result was equivocal (4.7%). CTC is an accurate, well-tolerated procedure and should be regarded as the method of choice for investigation of this condition. PMID- 8519148 TI - A radiological study of abdominal tuberculosis in a Saudi population, with special reference to ultrasound and computed tomography. AB - The radiological appearances of abdominal tuberculosis are presented, which includes peritoneal, liver, spleen and pancreatic disease, but excludes renal and musculoskeletal involvement. Twenty-three patients were studied, 12 of whom had TB peritonitis. Barium studies remain valuable in gastrointestinal tract disease but for peritoneal, splenic, hepatic and pancreatic disease, ultrasound and computed tomography are indicated. Their diagnostic value is further enhanced by guided aspiration and biopsy techniques. PMID- 8519149 TI - Mediastinal widening--a valuable radiographic sign of superior vena cava thrombosis. AB - Thrombosis due to indwelling intravenous catheters has become increasingly recognized as an important cause of the benign superior vena cava (SVC) obstruction. We evaluated the PA chest radiographs of nine patients with SVC thrombosis related to Hickman catheter insertion. All nine patients showed mediastinal widening at the time of developing SVC thrombosis and four patients had radiographic signs before the onset of symptoms. Five patients demonstrated lateral displacement of the Hickman catheter with the development of SVC thrombosis. The development of superior mediastinal widening is a valuable sign of SVC thrombosis and its recognition may allow earlier diagnosis and treatment of this condition. PMID- 8519150 TI - Liver hamartomas in tuberous sclerosis. AB - Three patients with tuberous sclerosis (TS) and hepatic hamartomas are presented. Liver lesions are uncommonly documented in TS, compared to renal angiomyolipomas. The imaging characteristics of liver hamartoma in TS may resemble those of renal angiomyolipoma, hepatic cavernous haemangiomas, metastasis or abscess. PMID- 8519151 TI - Soft tissue neck radiography for displaced dental prostheses. AB - Modern dental prostheses continue to be made of acrylic resins which can be difficult or impossible to recognize by conventional radiography. We discuss the difficulties that can arise and the recognition of such objects in the neck using three illustrative cases. PMID- 8519152 TI - Case report: combined conservative and percutaneous management of a perforated duodenal ulcer. AB - A case is presented of perforated duodenal ulcer with associated abscesses treated by percutaneous drainage in a patient with markedly impaired respiratory function. The potential role of conservative management in such patients is discussed. PMID- 8519153 TI - Case report: pelvic pain syndrome--successful treatment of a case by ovarian vein embolization. AB - Pelvic pain syndrome, without an apparent organic cause, is a common gynaecological complaint. Investigations, including laparoscopy are frequently negative but ovarian venography has demonstrated that pelvic varices are a consistent finding in these patients. The aetiology of pelvic varices has been the subject of debate, but it has recently been suggested that the primary problem is venous reflux in dilated, incompetent ovarian veins. Surgical ligation of the ovarian veins has been used effectively in small series of patients with this condition. We report a patient with the clinical and radiological features of this syndrome in which treatment by bilateral ovarian venous embolization produced prolonged symptomatic relief. PMID- 8519154 TI - Case report: papillary adenoma of the gall-bladder in a child of 9 years. AB - Gall-bladder neoplasms are unusual in childhood and are often not suspected clinically. We wish to report this unusual case of papillary adenoma of the gall bladder in a 9-year-old male child who had presented with clinical features of acute cholecystitis. PMID- 8519155 TI - Case report: ultrasound demonstration of traumatic fracture of the pancreas with pancreatic duct disruption. AB - Fracture of the pancreas is a rare injury caused by blunt abdominal trauma. Abdominal CT is probably the best modality for the detection of this uncommon injury. Ultrasonography is excellent for demonstrating an accompanying pseudocyst, but it is otherwise considered less effective than CT in the evaluation of pancreatic trauma. We report a case where we were able to demonstrate a fracture through the body of the pancreas along with disruption of the pancreatic duct, using a conventional ultrasound scanner. PMID- 8519156 TI - Colour Doppler imaging. PMID- 8519157 TI - General practice requests for lumbar and cervical spine radiograms: a survey of 30 radiology departments' routine views. PMID- 8519158 TI - Plasma exudation and solute absorption across the airway mucosa. AB - The airway mucosa responds to inflammatory provocations with bulk exudation of plasma into the airway tissue (vascular exudation) and lumen (mucosal exudation). The intensity and time course of the exudative response can be relevantly examined by sampling and analysing airway surface liquids, because the luminal entry of plasma proteins/tracers promptly and quantitatively reflects the exudative response of the airways. The process of mucosal exudation of plasma is a prominent feature of airway inflammation and has been demonstrated in rhinitis, asthma, and bronchitis. Inflammatory mediators and allergen produce mucosal exudation of plasma into the airway lumen (outward permeability) whereas the solute absorption across the mucosa (inward permeability) is unaffected. Hence, in contrast to current views, we have demonstrated that in airway inflammation the solute absorption across the airway mucosa is not increased. The findings suggest the plasma exudation response also as a first line respiratory mucosal defence, allowing potent plasma protein systems to appear on an airway mucosa functionally intact as a barrier toward undue luminal material. Our data on plasma exudation and solute absorption across the mucosa of upper and lower airways further suggest the human nasal airways as a model relevant also for the tracheobronchial airways. PMID- 8519159 TI - The effect of increasing temperature on skin blood flow and red cell deformability. AB - Using laser Doppler techniques in nine healthy volunteers, we contrasted the effect of increasing local skin temperature at the elbow, a skin site with nutritive microvasculature, and the finger pulp, with predominantly arteriovenous anastomic (AVA) perfusion). We also assessed flow at the finger dorsum, with contributions of both types of microvasculature. In parallel with the laser Doppler studies, we determined the effect of increasing temperature on the red cell deformability of our subjects, using the new technique of Cell Transit Time Analysis (CTTA). Thermal stimulation produced very large increases in skin blood flow at all three sites tested. However, the magnitude and the pattern of increase were different at the three sites. At the finger pulp, there was a linear approximately threefold increase in flow as temperature increased from the basal level to 44 degrees C. At the elbow, basal flow was considerably lower than at the finger pulp and increased very slowly until skin temperature reached 38 degrees C. From that point, flow increased sharply, reaching tenfold the basal level at 44 degrees C. The thermally induced increase at the finger dorsum was intermediate between the other two sites, with a pattern resembling the elbow more than the finger pulp. These differences among the sites were attributable to substantially different patterns of change in the two components of flow, microvascular volume and velocity. At the finger pulp, there was very little increase in microvascular volume with increasing temperature. The curve was practically flat from basal temperature to 44 degrees C. In contrast, there was a linear increase in red blood cell velocity of about 300%. At the elbow, both microvascular volume and red blood cell velocity exhibited a parallel curvilinear pattern of equivalent increase, on the order of 300% for each. There was only a small increase in both parameters until the temperature reached 38 degrees, at which point there was a sharp increase in both. At the finger dorsum, the situation was intermediate, again resembling the elbow more than the finger pulp. Cell Transit Time Analysis revealed a progressive decrease in red cell transit time (TT), from 3.28 ms at 28 degrees C to 2.48 m at 44 degrees C, an overall change of 24%. The decrease in TT was accompanied by an increase in transit frequency, measured as counts s-1 (C s-1), from 3.1 to 5.3, an overall change of 71%. The changes in both TT and C/S were essentially linear.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519160 TI - Effect of nifedipine on splanchnic and pulmonary vascular capacitance. AB - This study examines the hypothesis that nifedipine may increase splanchnic vascular capacitance and thus change the distribution of blood between the splanchnic and pulmonary circulation in heart failure patients. Relative regional blood volumes were determined by equilibrium blood pool scintigraphy during a 10 min baseline period and for 30 min after nifedipine 20 mg sublingually, with simultaneous recordings of systemic and pulmonary arterial pressures, hepatic venous wedge pressure, and cardiac output. Eight patients with ischaemic heart failure received nifedipine. Four patients served as controls. Nifedipine reduced mean arterial pressure and systemic vascular resistance in every patient. There were no significant changes in the relative blood volumes of the intestinal, hepatic, or splenic regions or in hepatic venous wedge pressure (reflecting portal venous pressure), suggesting unchanged splanchnic vascular pressure-volume relationship. Nifedipine caused a 6.3 +/- 1.0% increase in relative pulmonary blood volume and a slight increase in pulmonary vascular distending pressure from 16.1 +/- 2.9 mmHg to 17.5 +/- 2.8 mmHg (P < 0.05), suggesting that the increase in pulmonary blood volume was passively mediated. In conclusion, nifedipine did not change splanchnic vascular capacitance, but caused a small increase in pulmonary blood volume, which probably was a passive response to increased distending pressure. PMID- 8519161 TI - Maintained hyperexcretion of thromboxane A2 metabolite in healthy young cigarette smokers: results from a prospective study in randomly sampled males with stable smoking habits. AB - Although several studies have identified cigarette smoking as a factor increasing platelet formation of thromboxane A2 (TxA2), no prospective data on this issue have been presented in a defined population with stable smoking habits. Therefore, we analysed the relation between smoking habits and urinary excretion of the 2,3-dinor metabolites of thromboxane A2 (Tx-M) and prostacyclin (PGI-M) in 87 males, randomly sampled from a population of 18-19-year-old men, at two different occasions separated by 31-49 months. The daily cigarette consumption among the smokers was unchanged between the study occasions (11 vs. 11 cigarettes day-1), but 9 of 43 initial smokers had quit. None of the initial non-smokers had begun smoking. Tx-M was higher in the smokers than in the non-smokers and correlated with the daily cigarette consumption both at the initial (176 vs. 123 pg mg-1 creatinine; P = 0.01) and the second (214 vs. 164 pg mg-1; P = 0.002) study occasion. Those who had quit smoking since the initial study did not differ in Tx-M from the non-smokers at the second study occasion. Urinary PGI-M did not differ between cigarette smokers, non-smokers and quitters at either of the study occasions. We conclude that cigarette smoking elicits an increased formation of thromboxane A2, indicating platelet activation, that is stable during an observation period of up to 4 years. The increased platelet activity is reversible upon quitting. PMID- 8519162 TI - No effect of carbohydrate feeding on glycogen synthase in human muscle during exercise. AB - The effect of carbohydrate (CHO) feedings on exercise-mediated changes in glycogen synthase fractional (GSF) activity has been investigated. Subjects cycled at approximately 70% of maximal oxygen uptake on two occasions: the first to fatigue (135 +/- 17 min; mean +/- SE) (control, CON), and the second at the same workload and duration as the first, but with the addition of frequent ingestion of CHO during exercise (0.27 g kg-1 body weight every 15 min). Biopsies were taken from the quadriceps femoris muscle before and immediately after exercise. Plasma glucose and insulin decreased during CON exercise, but remained elevated throughout CHO exercise (end of exercise: glucose = 4.4 +/- 0.2 mM CON vs. 5.8 +/- 0.2 CHO, P < 0.01; insulin = 9 +/- 1 uU ml-1 CON vs. 19 +/- 3 CHO, P < 0.05). Glycogen decreased to approximately 10% of the basal value during CON and to approximately 20% during CHO, and there was no significant difference in net glycogenolysis between treatments. GSF activity averaged 0.25 +/- 0.03 and 0.22 +/- 0.05 at rest, and increased to 0.51 +/- 0.08 and 0.48 +/- 0.09 after exercise in CON and CHO, respectively (P > 0.05 between treatments). It is concluded that under the present conditions CHO feedings do not alter the exercise-mediated changes in GSF activity. The increase in GSF during exercise is attributed at least in part to the decrease in muscle glycogen (which increases the suitability of GS as substrate for GS phosphatase). PMID- 8519163 TI - Effects of cold pressor test on circulating atrial natriuretic peptide 99-126 (ANP) in patients with Raynaud's phenomenon and influence of treatment with magnesium sulphate and nifedipine. AB - The effect of a standardized cold pressure test (CPT) on the venous concentration of immunoreactive atrial natriuretic peptide (irANP) was studied in 12 females with primary Raynaud's phenomenon (PRP) and 12 female age-matched controls. The test was performed at the end of three stages. During the first stage no medication was given. During the second stage a magnesium infusion was given. After fourteen days of medication with a calcium antagonist (Nifedipine) the third stage of the study was performed. The venous irANP increased significantly (P < 0.05) 10 min after the start of the CPT both in the PRP group and in the control group (136 +/- 39 to 159 +/- 54 and 153 +/- 45 to 179 +/- 40 pg ml-1, given as mean and SD). Baseline irANP did not change in the PRP group after treatment with magnesium or nifedipine. In the control group nifedipine treatment significantly (P < 0.01) lowered venous irANP compared to the no treatment or magnesium sulphate infusion stages (128 +/- 31 vs. 153 +/- 45 and 160 +/- 41 pg ml-1). After the CPT in both PRP group and control group the venous irANP did not increase either during magnesium sulphate infusion or nifedipine treatment. In conclusion the study has demonstrated that a standardized CPT results in a delayed increase in irANP in venous plasma and that magnesium sulphate infusion and nifedipine treatment prevent this increase. Furthermore, our data do not suggest a role for irANP in the symptomatology of primary Raynaud's phenomenon. PMID- 8519164 TI - Cardioinhibitory-vasodepressor response to head-up tilt without hypoxaemia or myocardial ischaemia. AB - We evaluated whether hypoxaemia and/or myocardial ischaemia are of importance for development of the bradycardic hypotensive phase (cardioinhibitory-vasodepressor syncope) of central hypovolaemia. Arterial blood gas variables and a twelve-lead electrocardiogram (ECG) were followed during head-up tilt in seven men. During tilt, before presyncopal symptoms appeared, mean arterial pressure (MAP) increased (from 67 +/- 7 to 78 +/- 6 mmHg) (mean +/- SE) as did heart rate (HR) (61 +/- 4 to 99 +/- 8 beats min-1) and total peripheral resistance (TPR) (11 +/- 1 to 17 +/- 1 mmHg min l-1) (P < 0.01), while cardiac output (5.9 +/- 0.5 to 4.6 +/- 0.6 l min-1) and central venous pressure (CVP) (4.2 +/- 0.4 to 1.3 +/- 0.7 mmHg) decreased (P < 0.01). After 40 +/- 7 min of head-up tilt presyncopal symptoms appeared together with a decrease in MAP to 48 +/- 7 mmHg, HR to 71 +/- 11 beats min-1 and TPR to 9 +/- 2 mmHg min l-1 (P < 0.01). Arterial oxygen tension was not changed and there was no ST-segment depression of the ECG. The results indicate that during central hypovolaemia decreases in HR and TPR are elicited during normoxaemia and without electrocardiographic signs of myocardial ischaemia. PMID- 8519165 TI - Pulmonary arterial wedge pressure measurement can modify pulmonary haemodynamics in patients with chronic lung disease. AB - In 20 patients with chronic lung disease in stable condition, haemodynamic values were compared during wedging of a Swan-Ganz catheter, either in a distal branch of the pulmonary artery, or by balloon inflation (with 1 ml) in a proximal branch, mostly excluding right lower lobe perfusion. Average pulmonary arterial wedge pressure, systemic arterial pressure, transcutaneous and mixed venous oxygen saturation, cardiac output and pulmonary blood volume (PBV) were not statistically different during distal and proximal wedging, but systolic pulmonary arterial pressure and pulmonary vascular resistance were slightly higher during balloon inflation (P < 0.05). In four patients, PBV decreased by 20% or more; cardiac output was reduced and mean systemic arterial pressure diminished by 10 mmHg or more in three patients. Of the two patients with the lowest PBV, one did not tolerate the balloon inflation because of dyspnoea, and the other showed dramatically haemodynamic changes. These were more likely to occur when the occlusion lead to the exclusion of a still well perfused area. Our results support optimal matching between ventilation and perfusion in patients with chronic lung disease, although both are inhomogeneous. When pulmonary vascular restriction can be suspected, pressure obtained during catheter wedging by balloon inflation should be interpreted with caution. Monitoring arterial oxygen saturation and systemic arterial pressure before and during the manoeuver could help to diagnose haemodynamic effects of the balloon inflation in a proximal pulmonary artery. PMID- 8519166 TI - Stress hormones alter the pattern of free amino acids in human skeletal muscle. AB - Stress hormones were infused for 6 h in healthy volunteers (n = 32). Free amino acid concentrations were determined in plasma and in skeletal muscle biopsy specimens. A triple hormone combination of adrenaline, cortisol, and glucagon raised the level of alanine in muscle, while glutamine, glutamate, the branched chain amino acids, the aromatic amino acids, and the basic amino acids decreased. Adrenaline alone partly reproduced this pattern, while a 6-h infusion of cortisol left the muscle free amino acids unaffected. In plasma all individual amino acids except alanine and glutamate decreased in the subjects receiving adrenaline or a triple-hormone combination. Altered plasma amino acid concentrations did not necessarily reflect changes in the tissue amino acid content. It is concluded that an infusion of a triple combination of stress hormones into healthy volunteers produces changes in muscle amino acid metabolism similar to those seen immediately after surgical trauma. PMID- 8519167 TI - Approaching the surgical patient. Role of the medical consultant. AB - Medical consultants will no longer "clear patients" but will "prepare them" for surgery instead. They will be required to possess the expertise in assessing a patient's risk for surgery, managing perioperative medications, caring for postoperative complications, maintaining appropriate conduct in the role as consultant, and recording accurate documentation of level of service for third party reimbursement. PMID- 8519168 TI - Cardiorespiratory effects of anesthesia. AB - The basic objectives of any anesthetic are to provide the patient with safe analgesia and amnesia and to provide the surgeon with adequate conditions to perform the surgical procedure. This article discusses the different routes through which these objectives may be met. PMID- 8519169 TI - Indications for preoperative pulmonary function testing. AB - Atelectasis, hypoxemia, pneumonia, and respiratory failure are pulmonary complications that can follow surgical procedures. This article discusses controversies surrounding the use of preoperative pulmonary function testing to identify high-risk surgical candidates. Physiologic assessments based upon the nature of the contemplated procedure are recommended. PMID- 8519170 TI - Respiratory physiology in upper abdominal surgery. AB - This article describes the pathophysiology of the respiratory system after upper abdominal surgery, emphasizing the role of respiratory muscle dysfunction. The history of current techniques to measure respiratory muscle function are reviewed. The authors describe the postoperative pattern of breathing, speculate on the physiologic mechanisms responsible and discuss the data supporting the role of reflexes arising from the abdomen and the shift of neural output to different respiratory muscles. Finally, the authors review the impact of "closed" surgical interventions such as laparoscopic cholecystectomy. PMID- 8519171 TI - Perioperative respiratory care of the patient undergoing upper abdominal surgery. AB - The respiratory system is invariably affected during and after abdominal surgery. In high-risk patients, this may result in the development of postoperative pulmonary complications (PPC). Several pulmonary and nonpulmonary risk factors have been identified as good predictors for PPC. This article summarizes the treatments that may help prevent the development of PPC in patients undergoing upper abdominal surgery. PMID- 8519172 TI - Cardiac risk evaluation and management in noncardiac surgery. AB - A careful history, physical examination, resting electrocardiogram, and chest radiograph are essential for preoperative cardiac assessment of adult patients. The nine individual Goldman indicators of increased perioperative cardiac risk and evidence of an unstable coronary ischemic syndrome should be specifically sought in each patient and treated when possible. After initial assessment, patients who still have a medium level of perioperative risk can usually be accurately assigned to a high- or low-risk category through the use of exercise testing and the selective use of dipyridamole thallium imaging. PMID- 8519173 TI - Perioperative respiratory management in cardiac surgery. AB - The perioperative respiratory care of the cardiac surgical patient can present many challenges to the caring physician that he or she may not see among the usual patient population. Knowledge of the effects of the heart-lung machine on pulmonary performance, awareness of the anatomic changes brought on by the surgeon, and consideration of the patient's baseline cardiac and pulmonary function need to be addressed so that the pulmonary problems that they present can be managed optimally. PMID- 8519174 TI - Physiology of lung resection. AB - Although we speak intuitively about the effects of lung resection, little thought is given to the precise physiologic mechanisms. The effects of different thoracic incisions on the chest wall mechanics, the removal of pulmonary parenchyma on lung function, and the interaction of the cardiopulmonary apparatus all combine to result in specific physiologic derangements after thoracic surgery. PMID- 8519175 TI - The physiologic evaluation of the lung resection candidate. AB - The evaluation of patients with lung cancer should include an assessment of physiologic risk. This assessment begins with simple pulmonary function studies such as spirometry and diffusing capacity. Abnormalities of these test results should stimulate further assessment with quantitative lung scanning and noninvasive exercise testing. Resection should not be recommended in patients with extremely high risk; however, because of the poor prognosis, patients must be integrally involved in the decision to not resect the lung cancer. PMID- 8519176 TI - Perioperative management of the thoracotomy patient. AB - The perioperative management of the thoracotomy patient must be both specific and flexible. The assessment of preoperative information yields information as to operability and resectability. Once anesthesia is administered for operative procedures, however, techniques and methods must be changed to accommodate additional information obtained during the surgical procedure. The preoperative and intraoperative management is focused on improving pulmonary function during the postoperative period and improving outcome. Significant advances in pain management techniques have evolved within the last 10 to 15 years. Relieving the intense pain associated with a thoracotomy incision not only improves patient well-being, but improves breathing patterns and pulmonary function, resulting in a more comfortable and ambulatory patient. Epidural analgesia, intrathecal analgesia, intrapleural installation of local anesthetics, and PCA are but a few of the techniques that enhance the therapeutic armamentarium and improve the postoperative course. Inasmuch as surgical extirpation of lung cancers remains the best hope of survival for many patients, a detailed and aggressive management plan is necessary to achieve the desired result. PMID- 8519177 TI - Clinical aspects of lung transplantation. AB - Lung transplantation, which was a universally unsuccessful procedure at the start of the last decade, has now become a viable therapeutic option. Improvements in operative technique, patient selection, and immunosuppression have contributed to the dramatic improvement in outcome. Few aspects of lung transplantation are standardized, and the procedure is being continually refined. Actuarial 1 year survival rates are approaching 70%, and it appears that these rates will continue to improve. Scarity of donor lungs is rapidly becoming a serious impediment to the performance of lung transplantation in the United States. PMID- 8519178 TI - Reconstruction of the hypopharynx and cervical esophagus. PMID- 8519179 TI - The parabens: paradoxical preservatives. PMID- 8519180 TI - Sunscreen dermatitis: Part III--The benzophenones. PMID- 8519181 TI - Pediculosis capitis. PMID- 8519182 TI - A dermatologic diary. Portrait of a practice. PMID- 8519183 TI - Paraquat. PMID- 8519184 TI - Pen push purpura: iatrogenic nail bed hemorrhages in the intensive care unit. AB - Peculiar fingernail hemorrhages appeared in a febrile, comatose patient several weeks after she was admitted to the hospital. Bedside questioning of the nursing staff uncovered a frequently used neurologic examination maneuver as the cause. We suggest the term "pen push purpura" to describe this phenomenon. The clinical significance and various causes of nail bed hemorrhages are reviewed. PMID- 8519185 TI - Honeysuckle contact dermatitis. AB - A case report and discussion of linear itchy raised blisters on the wrist of a patient that pulled Hall's Japanese honeysuckle (Lonicera japonica holliana) is presented. PMID- 8519186 TI - Tertiary pinta: case reports and overview. PMID- 8519187 TI - Systemic lupus erythematosus with pigmented skin. AB - The authors present the case of a thirty-six-year-old woman with systemic lupus erythematosus with specific vesiculobullous symptoms. Degos dermal infarcts and Schonlein-Henoch-type purpura was observed in the course of her illness. Attention is drawn to the rarity of this symptom group, which has not been documented in previous publications. Degos lesions accompanying the systemic lupus erythematosus were benign. The effectiveness of sulfone in the treatment of vesiculobullous symptoms in this case is noted. PMID- 8519188 TI - A new neurocutaneous syndrome: nevus sebaceus syndrome. AB - We describe a case of nevus sebaceus syndrome characterized by a linear sebaceous nevus, extending on the left half of the face from forehead to lower neck, including the auricle; alopecia on the temporoparietal region; generalized hypotonia; insufficiency of eyes in following moving objects and insufficiency in controlling the head; lipodermoid cysts in the left and right eyes; bilateral conjunctival masses; corneal vascularization in the right eye; coloboma of the left eyelid and right optic disc. This is a rare case of a sebaceous nevus occurring concomitantly with optical and central nervous system abnormalities. PMID- 8519189 TI - A case of kwashiorkor. AB - Kwashiorkor is part of the spectrum of protein-energy malnutrition. The condition results from a lack of nutritional protein coupled with carbohydrate excess. Protein malnutrition is much more common in the Third World; however, it is also the most common form of nutritional deficiency among hospitalized patients in the United States. Cutaneous clues to the diagnosis of protein deficiency include the "flag sign," hypochromotrichia, alopecia, "crazy pavement" dermatosis, pallor, and glossitis. Systemic manifestations include peripheral edema, liver disease, neurologic changes, diarrhea, weight loss, and hypoalbuminemia. We report here a case of profound kwashiorkor in a nonhospitalized patient who presented with multiple cutaneous and systemic findings indicative of protein malnutrition. PMID- 8519190 TI - A facial variant of steatocystoma multiplex. AB - A case of steatocystoma multiplex confined to the face is reported. Review of the literature disclosed similar cases in this striking location. We therefore believe that this facial variant is a distinctive but less well known variant of steatocystoma multiplex. We review the relationship between steatocystoma multiplex and eruptive vellus hair cysts. PMID- 8519191 TI - Angiosarcoma of the face and scalp. AB - A case of angiosarcoma of the head and neck is presented. A review of the clinical and histopathologic features of this tumor is presented. PMID- 8519192 TI - Erythema multiforme (Stevens-Johnson syndrome) following deep radiation therapy. AB - Generalized eruptions following radiation therapy are rare. Most reported cases involve deep x-ray therapy for underlying cancer. We report a patient who experienced Stevens-Johnson syndrome following radiation therapy and present a review of the literature. PMID- 8519193 TI - Needle aspiration biopsy of the thyroid: revisited. PMID- 8519194 TI - Immunophenotyping of cytologic specimens by flow cytometry. AB - Immunophenotyping by flow cytometry is well established as an ancillary technique in the diagnosis of hematopoietic neoplasms. However, flow cytometry is rarely performed on cytologic specimens because most cytologist are more comfortable with direct microscopy and believe that there is inadequate cellularity for analysis. Paradoxically, cytologic material is usually cell suspensions making it ideal for flow cytometry. In order to evaluate the usefulness of immunophenotyping cytologic specimens by flow cytometry, we retrospectively reviewed all cytologic specimens submitted to our flow cytometry unit from 1988 to 1991. Thirty-one cerebrospinal fluid specimens were analyzed. There were inadequate cells for analysis in 15 cases. Five showed a monoclonal proliferation; 11 were nondiagnostic. A range (r) of one to six cell surface markers were performed. Thirty-two body cavity fluids were analyzed: 7 peritoneal, 19 pleural, 2 pericardial, and 4 bronchoalveolar lavage. There were cells to analyze in all cases. Seven had a monoclonal proliferation; 25 were nondiagnostic (r = 4-21 markers performed). One hundred eighteen fine needle aspirates (FNA) were reviewed; 58 FNA were radiologically guided, 60 were superficial lesions. There were inadequate cells for analysis in two cases. Sixty one demonstrated a monoclonal proliferation; 55 were nondiagnostic (r = 1-22 markers performed). We conclude that immunophenotyping by flow cytometry is of limited value for cerebrospinal fluid analysis and that knowledge of previous immunophenotyping studies is essential for correct analysis; analysis of body cavity fluids is easily performed but less often demonstrates a monoclonal proliferation. Immunophenotyping by flow cytometry is a valuable adjunctive technique for FNA and yields adequate cells for analysis. PMID- 8519195 TI - Cytologic features of metastatic transitional cell carcinoma. AB - Cytologic preparations containing metastatic transitional cell carcinoma (MTCC) from 18 sites in 16 patients were reviewed to determine characteristic morphologic features. The patient group included 13 males and 3 females with a mean age of 66 years. Primary TCC occurred in the bladder (14), kidney (1), and ureter (1); nearly all the primary tumors were poorly differentiated and most were invasive at the time of diagnosis. The cytologic specimens were derived from lymph nodes (6), liver (4), serous fluids (2), pelvic soft tissue (2), subcutaneous nodules (2), and lung (1). One patient presented with MTCC in Pap smears. Cytologically MTCC presented as loosely cohesive, moderate to markedly pleomorphic cells which occurred singly and in syncytial clusters. The malignant cells were usually large with abundant granular or fibrillar cytoplasm and the cell borders were generally distinct. Most nuclei were large and hyperchromatic with irregularly distributed granular chromatin and prominent nucleoli. The most distinctive features were the presence of spindled, pyramidal, and/or racquet shaped malignant cells with eccentric nuclei and cytoplasmic features of both squamous and glandular differentiation including endoplasmic/ectoplasmic interfaces and intracytoplasmic vacuoles. Although clinical history is most useful in the diagnosis of MTCC, these morphologic features in cytologic preparations of malignant epithelial neoplasms may be helpful. In the absence of a known primary TCC, it is doubtful that a definite cytologic diagnosis could be made; however, the characteristic cell shapes and cytoplasmic features may be suggestive of MTCC. PMID- 8519196 TI - Fine-needle aspiration cytology of sclerosing hemangioma of the lung: case report with immunohistochemical study. AB - Sclerosing hemangioma of the lung (SHL) is a rare benign neoplasm, usually found incidentally on a routine chest X-ray. We present a case of SHL initially diagnosed by fine-needle aspiration cytology. Cytomorphologic characteristics were confirmed by a cell block examination and immunohistochemical findings. The differential diagnoses of the fine-needle aspiration are discussed. PMID- 8519197 TI - Ameloblastoma of the mandible: diagnosis by fine-needle aspiration cytology. AB - The fine needle aspiration cytologic findings of 3 cases of histologically proven ameloblastoma of the mandible are described. Tightly packed clusters of basaloid epithelial cells with palisading are a characteristic feature. Squamous differentiation was noted in all cases but was marked in one case seen as larger cells with central nucleus and abundant cytoplasm showing keratohyaline granules and whorls. A careful examination of the centrifuged sediment is important when fluid is aspirated as it may reveal a few characteristic clusters enabling a cytodiagnosis when supplemented by radiologic findings. PMID- 8519198 TI - Malignant cystic epithelial-stromal tumor of the prostate. AB - A huge cystic tumor in the pelvis of a 62-year old man, cytologically by fine needle aspiration biopsy, was composed of malignant spindle cells and transitional as well as glandular epithelial cells. Histochemical, immunostaining, and ultrastructural studies of the aspirated specimens and on the radically resected tumor indicated that the neoplastic cells are of prostatic fibroleiomyomatous stromal and epithelial origin. The lesion did not extend to the urothelium of the urinary bladder. This tumor resembles the rare cystadenoleiomyofibroma of the prostate, yet the cytologic abnormalities suggest a malignant potential. Long-term follow-up and recognition of additional cases are necessary to define the biologic behavior of this neoplasm. PMID- 8519199 TI - Cytology of thyroglossal cyst papillary carcinoma. AB - The cytologic and histologic features of two cases of carcinoma arising in thyroglossal cyst are reported. The carcinoma in both cases was papillary thyroid carcinoma. The aspirated cyst fluid in one case revealed only macrophages and benign squamous epithelial cells, while in the other case the cyst fluid showed cytologic features of papillary carcinoma including psammoma bodies and epithelial cells with papillary clustering, intranuclear cytoplasmic inclusions, and positive immunohistochemical reaction to thyroglobulin. PMID- 8519200 TI - Nodular fasciitis: spontaneous resolution following diagnosis by fine-needle aspiration. AB - Nodular fasciitis can be histologically mistaken for a sarcoma. Typical cases are less than 5 cm and enlarge rapidly over days or weeks before diagnosis. The natural history of nodular fasciitis is unknown, since the diagnosis is usually based on excised lesions. Fine-needle aspiration of nodular fasciitis has been described, and features benign-appearing spindle cells (singly and in groups), collagen, and myxoid material. We describe 11 cases in which nonsurgical observation led spontaneously to complete resolution. Our study includes 7 males and 4 females (24 to 73 years of age; median = 42). Lesions were located in the arm (4), thigh (3), temporal area (2), breast (1) and the parotid (1) and ranged from 0.5 to 5.0 cm. (median = 1.5). They had been present for from less than 1 to 4 weeks (median = 2). In 9 cases, spontaneous resolution occurred in from 3 to 8 weeks (median = 4). Two other patients were lost to follow-up for up to 11 months, after which resolution was noted. Small palpable masses in the subcutaneous soft tissues which evolve over a short period of time and show the cytologic features of nodular fasciitis should be managed nonsurgically. If resolution does not occur within a few weeks, surgery can then be performed. PMID- 8519201 TI - Fine-needle aspiration biopsy of subcutaneous fat necrosis of the newborn. AB - This report provides the first description of the fine-needle aspiration biopsy findings in a case of subcutaneous fat necrosis of the newborn. While initial interpretation of the aspirate smears was suspicious for a neoplastic process, subsequent incisional biopsy confirmed the benign nature of the lesion. Review of the cytologic material revealed rare, negatively stained, needle-shaped crystals within histiocytes and multinucleate giant cells. In the appropriate clinical setting, and given a mixture of lymphocytes, histiocytes, and multinucleate giant cells in the aspirate smears, we believe the finding of negatively stained needle shaped crystals can strongly suggest the diagnosis of subcutaneous fat necrosis of the newborn. PMID- 8519202 TI - Diagnostic pitfalls in thyroid fine-needle aspiration: a review of 394 cases. AB - To determine the diagnostic pitfalls of thyroid fine-needle aspiration (FNA), we reviewed 394 thyroid aspirates obtained between January 1986 and December 1990. Surgical follow-up was available for 150 aspirations. The cytologic diagnoses were categorized into four groups: benign, 57; indeterminate, 51; malignant, 33; and nondiagnostic specimen, nine. There were three false negative diagnoses (3%), which upon review were judged to be inadequate specimens. Three false positive diagnoses (7%) were identified: in the first two cases, follicular adenomas were mistaken for papillary carcinoma; in the third case, atypical Hurthle cells were mistaken for a Hurthle cell carcinoma. Our results showed a sensitivity of 93% and a specificity of 91% for the detection of malignancy. If indeterminate cases were considered positive, the specificity decreased to 50%, while the sensitivity increased to 97%. We conclude that: 1) certain follicular adenomas may display cytologic features mimicking papillary carcinoma; 2) as in follicular neoplasms, aspirates of Hurthle cell adenomas cannot be differentiated from Hurthle cell carcinomas; 3) with adequate sampling, false negative results can be markedly reduced. PMID- 8519204 TI - Leiomyomata and leiomyosarcomata in HIV-infected children. PMID- 8519203 TI - Multinodular goiter of the thyroid mimicking malignancy: diagnostic pitfalls in fine-needle aspiration biopsy. AB - A case of multinodular goiter with multicentric papillary hyperplasia is presented with cytologic features suggestive of thyroid papillary carcinoma. While the cytologic criteria for papillary thyroid carcinoma is well defined, occasional diagnostic difficulties can arise. Cytologically, the presence of focal papillary aggregates, the presence of a psammoma body within a background of copious colloid and scattered follicular cells led to diagnostic confusion. Histologically, the presence of secondary follicles in the papillae and protrusion of the papillary structures into colloid lakes supported the diagnosis of goiter. It is our opinion that most, if not all, of these difficulties can be circumvented by the incorporation of all major and some minor cytologic criteria for papillary carcinoma in the analysis of such lesions. Single criteria for papillary carcinoma, either major or minor, is not sufficient. PMID- 8519205 TI - [Coronary angioplasty with controlled longitudinal dissection. Initial clinical results using a new cutting balloon]. AB - A recently developed cutting balloon was used for coronary angioplasty in 21 patients (4 women, 17 men; mean age 57.6 [36-81] years) with coronary heart disease (angioplasty of the right coronary artery in 4, of the circumflex branch in 4, and of the anterior interventricular branch in 13 patients). The balloon contains 3-4 longitudinally arranged metal cutters to prevent uncontrolled vessel tears. An average stenosis reduction from 84 +/- 8.6% to 30 +/- 10.6% was achieved in ten patients. In the eleven others a second dilatation with a conventional balloon was necessary because of a residual stenosis of over 50% after the first dilatation with the cutting balloon. This reduced the original stenosis from 78.6 +/- 9.4% to 30.4 +/- 9.9%. Complete occlusion at the place of previous dilatation occurred in one patient 14 hours after the procedure, due to a dissection which required a stent implantation. These preliminary results suggest that the cutting balloon can achieve a stenosis reduction similar to that with a conventional balloon. PMID- 8519206 TI - [Interstitial nephritis in typhus]. AB - A 58-year-old man developed continuous fever of around 40 degrees C and a macular rash on the trunk and limbs one week after an eight-day visit to the island of Rhodos. Typhus was diagnosed on the basis of the clinical findings, the characteristic rash and a rise in antibody titre against Rickettsia prowazekii and mooseri (1:1280). The fever subsided and the patient's general state markedly improved within three days of starting antibiotic treatment with doxycycline. Five days after hospital admission renal function deteriorated, serum creatinine rising from 1.7 to maximally 8.7 mg/dl. Renal biopsy on the eighth day of illness revealed, in concordance with the diagnosis of a rickettsial infection, acute granulomatous interstitial nephritis. Doxycycline administration was continued for a total of 18 days and renal function improved. Two weeks after discharge serum creatinine had fallen to 1.8 mg/dl and to 1.2 mg/dl after 6 months. The antibody titre against Rickettsia prowazekii had fallen to 1:20 about 12 weeks after discharge. Early antibiotic treatment of typhus is of importance to avoid irreversible renal damage. PMID- 8519207 TI - [Paracetamol poisoning in infancy]. AB - An eight-week old infant with alcohol embryopathy, weighing 3,700 g, was found to have abnormal liver functions (GPT 312 U/l, Quick value 25%) after surgical repair of a stenosis of the left ureter at its origin. The hospital notes indicated that the infant had been given a total of 1.6 g paracetamol over 60 hours for postoperative restlessness and pain. The serum paracetamol level was 60 mg/l 8 hours after the last dose of the drug. Blood exchange transfusion lowered the paracetamol level to 11 mg/l within 14 hours. After the exchange transfusion further signs of poisoning, namely renal impairment and a severe encephalopathy were noted, and Candida was demonstrated in urine, tracheal secretion and ascites. The renal and hepatic damage proved reversible under symptomatic treatment. But the child, now 1 year old, is severely retarded mentally and in its motor functions. These sequelae may be a residue of the paracetamol poisoning, complications of the clinical course or a combination of the two. PMID- 8519208 TI - [Pulmonary thromboembolism in antiphospholipid syndrome]. AB - A 37-year-old woman in acute right heart failure had experienced systemic venous thromboses for 17 years, five miscarriages and repeated pulmonary emboli. For the last 7 years she had been treated symptomatically for pulmonary hypertension. The platelet count was 62,000/microliters, thromboplastin time under phenprocoumon was 22%, partial thromboplastin time was 72 s. Despite anticoagulation with phenprocoumon and heparin (7,500 IU two times daily subcutaneously) new pulmonary emboli occurred and platelet count fell to 12,000/microliters. An increased titre for anticardiolipin antibodies (IgG > 320 GPL U/l, IgM 8 MPL U/l), antinuclear (1:640) and anti-ds-DNA antibodies (> 200 IU/ml) with simultaneous complement consumption suggested secondary antiphospholipid syndrome associated with lupus erythematodes. Treatment with prednisolone (150 mg/d), immunoglobulins (20 mg/d intravenously for 5 days) and heparin (25,000 IU/24 h intravenously) achieved an increase in platelet count to 200,000/microliters within 10 days, but fell again when the prednisolone dose was reduced, recovering under azathioprine, 150 mg/d. Four weeks later the patient died of renewed acute right heart failure. PMID- 8519209 TI - [Diagnosis of primary gastric lymphoma]. PMID- 8519210 TI - [Therapy of primary gastric lymphoma]. PMID- 8519211 TI - [Parathyroid hormone-related protein. A new calcium regulating hormone and its significance in tumor-associated hypercalcemia]. PMID- 8519212 TI - [Osteochondrosis dissecans]. PMID- 8519213 TI - [Safety measures in the production of cytostatic preparations]. PMID- 8519214 TI - [Therapy of heparin-induced thrombosis-thrombocytopenia syndrome using immunoglobulins]. PMID- 8519215 TI - [Fatal Salmonella enteritidis meningoencephalitis]. PMID- 8519216 TI - [The effect of intracoronary infused captopril on luminal width in coronary stenosis]. AB - To elucidate the mechanism of anti-ischaemic and anti-anginal action of angiotensin-converting-enzyme inhibitors, a randomized double-blind study was undertaken in 30 consecutive patients (27 men, 3 women; mean age 58 [28-70] years) with stable angina and at least 50%, angiographically well demonstrated, stenosis of one of the main coronary artery branches. They received an intracoronary infusion of either 0.5 mg captopril (n = 16) or of a placebo (n = 14) to see whether in this form of application the drug could cause an acute dilatation of a coronary stenosis. The diameter before captopril administration was 1.40 +/- 0.63 mm, while 1, 5 and 10 min after infusion it was 1.49 +/- 0.58 mm, 1.30 +/- 0.54 mm and 1.41 +/- 0.59 mm (not significant). There was also no significant difference between captopril and the placebo. The absence of effect with captopril may be due to insufficient liberation of endothelium-derived relaxing factor in an arteriosclerotic coronary segment. PMID- 8519217 TI - [Broad beans as a cause of acute hemolytic anemia]. AB - A previously healthy 17-year-old Greek boy suddenly developed jaundice of sclerae and skin. In addition, physical examination revealed a pale appearance. He also reported feeling tired and weak. The haemoglobin level was 9.6 g/dl, lactate dehydrogenase activity 335 U/l, bilirubin concentration 3.2 mg/dl (direct bilirubin 0.7 mg/dl, indirect bilirubin 2.5 mg/dl), haptoglobin concentration 48.8 mg/dl. As haemolytic anaemia was assumed, direct questioning elicited the fact that the patient had, for the first time in his life, eaten 300 g of broad beans (Vicia faba) on each of two days, namely 3 and 2 days before the appearance of jaundice. Absence of glucose-6-phosphate dehydrogenase activity in the red blood corpuscles confirmed the diagnosis of favism. On symptomatic treatment both the enzyme activities and the bilirubin level fell to normal within one week, and the haemoglobin level was 15.7 g/dl after 4 weeks. PMID- 8519218 TI - [Pulmonary angiodysplasia with fatal pulmonary hemorrhage]. AB - For 6 weeks a 52-year-old woman had complained of increasing fatigue, blood streaked vomitus, retrosternal burning and pain between the shoulder blades. Physical examination showed no abnormalities. Blood sedimentation rate was increased to 15/40 mm and the iron concentration was slightly reduced. Computed tomography demonstrated densities in the left upper lobe of the lung and both lower lobes. Scintigraphy revealed a perfusion defect in the left apex of the lung while bronchoscopy demonstrated acute bronchitis in the left upper lobe. Further haemoptysis occurred 3 months later, but several bronchoscopies failed to elucidate their cause. Three days later another haemoptysis caused respiratory arrest. After resuscitation the bleeding was localized to the right main bronchus, and the right upper and middle lobes were resected. The patient died the next day from a massive haemoptysis. Post-mortem examination showed angiodysplasia in all lobes of the lung. The branches of the pulmonary artery were dilated, their wall was irregular and the muscular tunica media reduced. The elastic lamellae were fragmented and there were cell-rich intimal pads. These changes most closely resembled fibromuscular dysplasia. PMID- 8519219 TI - [Spontaneous bacterial peritonitis in chronic liver disease with ascites]. PMID- 8519220 TI - [Functional brain disorders in old age]. PMID- 8519221 TI - [Peridural and general anesthesia]. PMID- 8519222 TI - [Adjuvant hormone therapy in breast carcinoma]. PMID- 8519223 TI - [Cryoglobulinemia and hepatitis C]. PMID- 8519224 TI - [Alleviation of colonoscopic sigmoid passage]. PMID- 8519225 TI - [Enzyme therapy of Gaucher's disease]. PMID- 8519226 TI - [Tetanus vaccine protection]. PMID- 8519227 TI - [Anaphylactic reaction during lipid pheresis and ACE inhibitor therapy]. PMID- 8519228 TI - [Current status of small intestine transplantation]. PMID- 8519229 TI - [Neuroendocrine function disorders following irradiation of brain tumors]. PMID- 8519230 TI - [Measurement of prothrombin fragment F1+2 for monitoring the anticoagulant effect of phenprocoumon]. AB - It was the aim of this study to ascertain whether the plasma level of prothrombin fragment F1+2 is a suitable indicator of the anticoagulant effect of coumarin derivatives. The F1+2 levels were measured in 164 patients (100 women, 64 men; mean age 63.3 [34-83] years) in whom stable anticoagulation had been achieved with phenprocoumon, comparing the results with those obtained in healthy subjects (28 women, 19 men; mean age 54.6 [25-72] years) without anticoagulation. There was a significant reduction (P < 0.0005) in F1+2 plasma levels with oral anticoagulation (0.45 + 0.23 vs. 0.67 + 0.32 nmol/l). Even on a low degree of anticoagulation (international normalized ratio [INR] < 2.0) the F1+2 value was reduced to within the normal range (0.32-1.2 nmol/l). These results indicate that changes in the plasma level of prothrombin fragment F1+2 are directly dependent on the degree of oral anticoagulation and that this measure seems suitable for the monitoring of the anticoagulant effect. This is also true for oral anticoagulation of mild degree (INR < 2.0) in which the effect cannot be satisfactorily measured by the thromboplastin time (Quick test). PMID- 8519231 TI - [Life-threatening arterial bleeding in hemorrhagic-necrotizing salmonella ileitis]. AB - A 23-year-old man in otherwise good health had diarrhoea for two days during a holiday on Maldives. Two months later he suddenly collapsed and had to be admitted to hospital. Haemoglobin concentration was found to be 76 g/l, with a haematocrit of 0.22, WBC count of 17,800/microliters and platelets of 22%. Massive passage of bright red blood in the stools (none previously) could not be explained by abdominal sonography, oesophagogastroduodenoscopy, coloscopy, technetium scintigraphy or angiography of the superior mesenteric artery. Exploratory laparotomy revealed severe inflammatory changes in the terminal ileum with enlargement of the regional lymph-nodes and spurting bleeding from a branch of the ileocolic artery. Histological examination showed focal necrotizing, ulcerative and haemorrhagic ileitis. After ileocaecal resection and end-to-end anastomosis to the ascending colon the patient quickly recovered. Salmonella Livingstone was isolated from the stool and the infection was treated with ciprofloxacin, 200 mg twice daily intravenously for 5 days. Subsequent stool samples were negative but follow-up continues. PMID- 8519233 TI - [Fundamentals and possibilities of intraoperative radiotherapy]. PMID- 8519232 TI - [Pulmonary valve endocarditis and atrial fibrillation]. AB - A 61-year-old man became ill with a fever of 39.4 degrees C, decreased exercise tolerance and headache as well as chest pain. Physical examination 3 weeks after the onset of symptoms merely revealed irregular heart rate at 100 beats/min. Erythrocyte sedimentation rate was increased (30/61 mm), as were serum bilirubin, lactate dehydrogenase, alkaline phosphatase, gamma-GT and C-reactive protein. The ECG showed atrial fibrillation with a rapid and irregular ventricular rate, as well as ventricular extrasystoles (Lown type IIIA), there were no abnormal findings on either the chest radiography or transthoracic echocardiography. Antiarrhythmic treatment brought about atrial flutter with 4:1 a-v conduction. Transoesophageal echocardiography now revealed vegetation on the pulmonary valve and microthrombi in the left atrial appendage. Ten days after starting intravenous penicillin G (10 mega units four times daily), gentamycin (60 mg three times daily) and heparin (30,000 units over 24 h) sinus rhythm was restored, the vegetation had got smaller and no thrombi were demonstrated. After 27 days antibiotic treatment was changed to oral penicillin V. After 4 weeks the patient was discharged symptom-free. PMID- 8519234 TI - [Treatment of multiple myeloma. Theoretical principles and clinical procedures]. PMID- 8519235 TI - [The end of the chief physician contracts upon reaching the age limit. Decision of the Hannover labor court on January 28, 1993]. PMID- 8519236 TI - [Aluminum accumulation and deferoxamine]. PMID- 8519237 TI - [Circadian variation of antibody formation after hepatitis B vaccination]. PMID- 8519238 TI - Treatment of difficult bile duct stones using mechanical, electrohydraulic and extracorporeal shock wave lithotripsy. AB - Over a 34-month period (1989-1991), 791 patients were diagnosed at endoscopic retrograde cholangiography to have bile duct stones. All patients underwent sphincterotomy and attempted extraction by Dormia basket. This was successful in 683 patients (86%). The remaining 108 patients with "difficult stones" (mean age 72 years) underwent mechanical, electrohydraulic or extracorporeal shock wave lithotripsy according to the following algorithm: (1) Mechanical lithotripsy for stones which could not be extracted after entrapment in the Dormia basket (n = 33); (2) peroral cholangioscopic electrohydraulic lithotripsy for stones which could not be engaged in the Dormia basket (n = 65); or (3) extracorporeal shock wave lithotripsy for intrahepatic stones (n = 10). Stone fragmentation and clearance was successful in all patients treated by mechanical lithotripsy, was unsuccessful in one patient submitted to electrohydraulic lithotripsy due to inability to insert the cholangioscope into the bile duct and failed in 3 patients treated by extracorporeal shock wave lithotripsy. Overall, 95% of difficult bile duct stones refractory to conventional endoscopic basket extraction were removed using the above lithotripsy techniques. There were no serious procedure-related complications. PMID- 8519239 TI - A prospective, randomized, controlled trial of metal stents for malignant obstruction of the common bile duct. AB - Endoscopic insertion of biliary stents is the preferred method of palliation for inoperable malignant biliary obstruction; however, migration and clogging are frequent problems with conventional endoprostheses. We sought to determine if expandable metal stents offer improved palliation compared to conventional stents. Sixty-two patients with common bile duct lesions were randomized to receive polyethylene or metal stents. Stents were placed endoscopically or by the combined percutaneous-endoscopic route. Early results (< 1 month) were similar in both groups. Long-term follow-up (n = 28 polyethylene, median: 5 months; n = 27 metal, median: 5 months) showed a higher stent failure rate in the polyethylene (n = 12; 43%) compared to the metal group (n = 6; 22%). The incidence of cholangitis was significantly higher (p < 0.05) in the polyethylene (n = 10; 36%) compared to the metal group (n = 4; 15%). Life-table analysis showed a significantly reduced incidence of stent failure (p = 0.0035) in the metal stent compared to the polyethylene group. The total duration of hospital stay for treatment of stent related problems was significantly higher in the polyethylene (11.8 +/- 3 days) compared to the metal group (4 +/- 1.9 days; p = 0.02). The costs for retreatment because of stent failure were significantly higher in the plastic (DM 5900 +/- 1516) compared to the metal group (DM 2070 +/- 977). As a result, the overall costs (treatment of stent related complications & stents) were higher in the polyethylene group (DM 6000 +/- 1500).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519240 TI - Endoscopic injection therapy of Forrest II and III gastroduodenal ulcers guided by endoscopic Doppler ultrasound. AB - Endoscopic Doppler ultrasound enables the reliable identification of vessels in the base of gastroduodenal ulcers. In a prospective study including 114 patients with acute ulcer bleeding, pulsed Doppler ultrasound was able to demonstrate superficial blood vessels in the ulcer base in 62% of 106 cases where complete Doppler assessment was possible (93%). Agreement between the endoscopic pattern of visible vessels and the Doppler ultrasound findings was attained in only 52% of the cases. Doppler positive ulcers (n = 66) were treated with injection therapy (if necessary, repeated), irrespective of their Forrest classification. Using such an approach, the rebleeding rate in this group decreased to less than 8% and none of the patients died of causes related to the hemorrhage. All Doppler negative ulcers (n = 40) healed without complications or the need for endoscopic treatment; among these were 11 cases with Forrest IIa and b. We conclude that endoscopic Doppler appears to be a valuable diagnostic procedure in the assessment of bleeding ulcers, thus modifying the Forrest classification. Our concept is that Doppler positive ulcers require local endoscopic treatment, whereas Doppler negative ulcers can be treated conservatively. PMID- 8519241 TI - Endosonography for preoperative locoregional staging of esophageal and gastric cancer. AB - To assess the accuracy and limitations of endoscopic ultrasonography (EUS) in the preoperative staging of esophageal and gastric carcinoma, we performed a prospective controlled study over a five year period. Data from 63 patients with esophageal cancer and 147 patients with gastric cancer who underwent surgery were available for comparison of the endosonographic TNM classification to the histophathological findings of the resected specimens. The overall accuracy of EUS in the assessment of tumor infiltration depth was 85.7% and 78% in esophageal and gastric cancer, respectively. The sensitivity of EUS in the detection of regional lymph node metastases was 90% in esophageal and 87% in gastric carcinoma. The most frequent causes of misdiagnoses by endosonography were microscopic tumor invasion and peritumorous inflammatory changes. The inability to traverse a tumor stenosis restricted the endosonographic evaluation in 31.6 and 14% of the cases with esophageal and gastric cancer, respectively. PMID- 8519242 TI - Endoscopic ultrasonography in the diagnosis of regional lymph nodes in esophageal and gastric cancer--results of studies in vitro. AB - A total of 90 regional lymph nodes (43 benign/47 metastatic) from 16 surgical resection specimens of patients with esophageal and gastric carcinoma were examined in vitro by endosonography. The validity of endosonographic criteria of lymph node dignity (size, echogenicity, internal echo pattern and margin structure) was assessed using computer-supported B-mode analysis and compared to histopathological results. Of 26 lymph nodes with a diameter of more than 10 mm, 19 were metastatic (72%). The subjective assessment of the internal echo pattern (homogeneity) and the node margins by an experienced observer allowed the diagnosis of metastatic lymph nodes, but there was a high proportion of false positives (52%). Lymph node echogenicity, assessed either subjectively or by computer analysis, did not permit the differentiation between benign and metastatic lymph nodes. PMID- 8519243 TI - New bougie applicator system for intraluminal "high dose rate" afterloading radiotherapy of esophageal carcinoma. AB - Applicators used to date in endoluminal "high dose rate" (HDR) afterloading (AL) radiotherapy of esophageal carcinoma consist of hollow plastic probes with an average thickness of 4 mm (1.8-5.0 mm), the diameter of which, however, often strongly deviates from that of the lumen of the tumor stenosis. Consequently, the probe can occupy an eccentric position in the esophagus. Exact dosimetry in the tumor region thus becomes virtually impossible, since the dose of the iridium emitter drops significantly with increasing distance (> 60% at a distance of 5 mm from the surface of the 4 mm probe). The bougie-type afterloading applicators developed by our group, however, offer a number of distinct advantages in comparison to conventional applicator probes: 1. Precise positioning of the applicator in the stenosis with simultaneous bougie effect. 2. Exact centering of the radiation source in the lumen of the esophagus. 3. Individual adaptation of the applicator size to the diameter of the residual lumen resulting from the tumor. 4. Upon patient-specific adaptation of the radiation exposure period, a distinct reduction of the surface (mucosa) dose is achieved together with simultaneous enhancement of the depth effect of radiotherapy treatment. Using these new afterloading bougies in over 150 treatment sessions involving 55 patients, no complications were thus far observed. PMID- 8519244 TI - Bleeding watermelon stomach treated by Nd-YAG laser photocoagulation. AB - We report on five patients with liver disease requiring blood transfusion because of recurrent acute or chronic bleeding from diffuse antral vascular ectasia (watermelon stomach). All were initially misinterpreted as hemorrhagic gastritis. Medical treatment with antiulcer drugs failed to control blood loss. Nd-YAG laser therapy (medium number of sessions: n = 4, range: 1-8) improved the endoscopic appearance of the gastric lesions and effectively controlled blood loss in all patients over a medium follow up period of eight months (range: 2-12 months). Treatment related complications did not occur. PMID- 8519245 TI - Endosonography in the diagnosis of lymph nodes. PMID- 8519246 TI - Ulcer bleeding stigmata: what is better than the endoscopist's eye? PMID- 8519247 TI - An unusual complication in attempted non-surgical treatment of pancreatic bile duct stones. AB - This report describes a guidewire fracture during an attempt at endoscopic treatment of pancreatic duct calculi in a patient with chronic pancreatitis, multiple pancreatic duct stenoses and pancreatic duct stones. This patient underwent endoscopic sphincterotomy in order to perform pancreatic duct drainage prior to ESWL. After sphincterotomy, a guidewire was introduced into the main pancreatic duct, but was jammed by the calculi. Neither could the guidewire be removed nor a contrast medium catheter be pushed over it, thus making ESWL impossible. A stronger pull resulted in a fracture of the wire, and a 25 mm long part which could not be removed with a Dormia basket remained in the main pancreatic duct. A Whipple's procedure became necessary as definitive treatment for the pancreatico-lithiasis in this patient. PMID- 8519248 TI - Guidewire fracture during endoscopic sphincterotomy. AB - Aberrant current conductance during an endoscopic sphincterotomy is a potential hazard. However, such complications have remained primarily theoretical. In this case report, we describe the fracture of a 0.018" Teflon-coated guidewire while performing a sphincterotomy with a 7 French, dual-chambered papillotome. The fractured guidewire was free and loose in the biliary tree, but was subsequently retrieved with endoscopic techniques. Inspection of the papillotome revealed charring of the plastic area adjacent to the cutting wire tip. The electrocautery unit was found to be in normal operating condition after formal testing. We speculate that the papillotome was defective, allowing current flow directly from the cutting wire to the guidewire. The small diameter guidewire then allowed a greater current density, resulting in heat which eventually contributed to fracture of the guidewire. Aberrant current can be conducted over a non-insulated guidewire. This potential hazard can be avoided with an insulated (coated) guidewire or removal of a non-insulated guidewire. PMID- 8519249 TI - Subserosal hematoma of the duodenum as a complication of diagnostic esophagogastroduodenoscopy. PMID- 8519250 TI - Hemoperitoneum due to necrosis of a small intestinal leiomyosarcoma following colonoscopy. PMID- 8519251 TI - Early retroduodenal perforation following endoscopic internal biliary drainage. PMID- 8519252 TI - Retropneumoperitoneum: an unusual case after colonoscopy. PMID- 8519253 TI - Avoiding omental entanglement at Verres needle insertion during laparoscopy. PMID- 8519254 TI - Recent controversy in radiation dosimetry. PMID- 8519255 TI - A simplified method for quantitation of iodine-123 iodobenzamide in human plasma: a technical note. AB - To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D2 dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (123I-IBZM) (a selective D2 ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of 123I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% +/- 0.3% (n = 15) for IBZM from plasma, while 99.3% +/- 0.2% (n = 12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy approximately 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D2 receptor density in vivo. PMID- 8519256 TI - Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease. AB - A loss of acetylcholine is one of the most consistent neurochemical findings in Alzheimer's disease (AD) post-mortem, but the debate concerning receptor abnormalities is unresolved. The aim of this investigation was to measure the density of acetylcholine muscarinic receptors in AD patients at various stages in the disease (N = 8) by synthesising a radio-iodinated version of quinuclidinyl benzilate QNB, a potent muscarinic antagonist. Deficits were identified by comparison with a control data set obtained from four elderly volunteers and then compared to the deficit in total functional activity in the same brain regions measured using the cerebral perfusion tracer technetium-99m hexamethylpropylene amine oxime. Iodine-123 (R,R)quinuclidinyl benzilate (QNB) was synthesised using a CuI assisted nucleophilic aromatic exchange reaction. 160 MBq of the radioligand (specific activity 400 Ci/mmol: dose 90 ng/kg) was administered to each subject. Diagnosis of AD was made using the CAMDEX and DSMIIIR criteria with a physical examination, full blood screen, CT and chest X-ray. All subjects were scanned at 21 h post injection on an SME810 emission tomograph. 123I(R,R)QNB activity in the controls was found to be consistent with the known distribution of muscarinic receptors with no activity in the cerebellum and low activity in the thalamus. In the AD patients deficits in 123I-QNB binding which exceeded the corresponding total functional regional perfusion deficit were not found in six of the patients and were observed only in the two most severely affected patients, both of whom were untestable on the cognitive battery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519257 TI - Reliability of low-frequency auditory stimulation studies associated with technetium-99m hexamethylpropylene amine oxime single-photon emission tomography. AB - Development of auditory stimulation tests associated with single-photon emission tomography (SPET) shows evidence of variations in perfusion related to the stimuli. Three brain SPET examinations with technetium-99m hexamethylpropylene amine oxime were performed on eight right-handed adults with normal hearing, the first one without stimulation and the other two associated with a 500-Hz/30-dB stimulation of the right ear. Temporal regions of interest covering auditory areas, as well as parietal ones (internal control), were drawn on three successive coronal slices. A cortico-cerebellar index R was calculated, and the variation in activity was defined for each subject using the ratio R poststimulation--R prestimulation/R prestimulation. A significant increase in the temporal cortex count occurred in all subjects. This increase was bilateral, except for one subject in whom it was not significant on the right side. This result recurred during the second stimulation study. Overall the response of the left temporal cortex was stronger, although the asymmetry was not significant. The asymmetry repeated itself after each stimulation. The perfusion response is globally reliable in our study. We must ascertain how sensitive this test is with regard to deaf adults and adults with normal hearing before extending its use to children. PMID- 8519258 TI - Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylpropylene amine oxime. AB - The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassen's correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor alpha was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/100 g/min on average. An increase in rCBF after acetazolamide administration was observed and measured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow. PMID- 8519259 TI - Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma. AB - We present a method to assess quantitatively the immunological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who was injected with 96.2 MBq of iodine-124 labelled 3F8, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1 = 0.048 ml h-1 g 1, k2 = 0.16 h-1, k3 = 0.03 h-1, k4 = 0.015 h-1 and BP = 2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement. PMID- 8519260 TI - False-positive thyroid cancer metastasis on whole-body radioiodine scanning due to retained radioactivity in the oesophagus. AB - In patients with differentiated thyroid cancer, radioiodine uptake in the mediastinal area most often indicates thyroid cancer metastasis. We review 15 radioiodine whole-body scans showing 19 mediastinal artefacts that mimicked lymph node or spinal metastasis. The artefacts disappeared on delayed images after eating and drinking (17) or on studies repeated within 1 week (2), suggesting their oesophageal origin. No patient had clinical oesophageal or gastric disease. Only two artefacts were linear; 12 were focal and five were diffuse. Twelve artefacts were better seen on anterior views (nine in the upper, two in the middle and one in the lower mediastinal area), whereas seven were better seen on posterior views (two in the upper, two in the middle, and three in the lower mediastinal area). The 15 scans were identified from about 1000 scans performed over 24 months in our centre. We conclude that the transient presence of radioiodine in an apparently normal oesophagus may not uncommonly mimic mediastinal lymph node or spinal metastases from thyroid cancer and that its scintigraphic presentation is variable. PMID- 8519261 TI - Intraoperative detection of pheochromocytoma with iodine-125 labelled meta iodobenzylguanidine: a feasibility study. AB - We evaluated the feasibility of intraoperative detection of pheochromocytoma sites after injection of meta-iodobenzylguanidine labelled with iodine-125. Six patients with multiple or recurrent pheochromocytoma were injected for intraoperative detection. During surgery, all count rates were recorded using a CdTe detector diode. Tumour foci were found in all cases. Tumour count rates ranged from 50 to 1000 counts per second (mean approximately 400). Blood activity, used as a reference level, ranged from 10 to 50 counts per second (mean approximately 35). In all patients, the intraoperative probe was helpful to the surgeon and facilitated the discovery of the pathological foci even when they were small (< or = 1 cm). Complete resection under probe control was correlated with postoperative normalization of urinary normetanephrine excretion. The use of a probe designed to detect low-energy gamma-ray radionuclides bound to a highly specific molecule provides an accurate detection tool which is well adapted for ectopic localizations and for small foci. PMID- 8519262 TI - Phantom studies in osteoporosis. AB - Differences in measurement results of bone densitometry are an obvious disadvantage of this method. The differences are mainly due to the calibration procedures for bone densitometry systems employed by the manufacturers, the software algorithms for defining the region of interest or edge detection, and the physiological inhomogeneity of body composition. Whereas intra-unit variation of reproducibility is acceptable, inter-unit variation may reach up to 20%. This paper discusses the problems of designing measurement phantoms and underlines the need for standardisation of phantoms for calibration, cross-calibration, and quality control in bone densitometry. A general phantom used for cross calibration should handle all parameters influencing measurement of bone minerals to yielded dynamic reference values. One has to note that densitometry systems do not measure the absolute bone mineral content but a model-related equivalent of the calibration material. PMID- 8519263 TI - Multidetector single-photon emission tomography: are two (or three or four) heads really better than one? AB - Today, almost every camera sold, with the exception of mobile systems, is "single photon emission tomography-capable". The atest technical development is the so called multidetector systems. This article reviews the development and current and potential clinical role of these multidetector systems, with particular emphasis on multicamera systems. The utility of multidetector systems is considered in the context of an image's signal-to-noise ratio, including its effect on diagnostic or quantitative accuracy. The potential for multidetector systems to increase the signal-to-noise ratio is discussed, as are other potential benefits. Finally, advice on an approach to equipment selection is provided. PMID- 8519264 TI - Effective dose from radiopharmaceuticals. PMID- 8519265 TI - Quality of life as context for planning and evaluation of services for people with disabilities. AB - Quality of life has become a dominant theme in planning and evaluating services for people with disabilities. This article reviews definitions of quality of life, explores the concept from the perspective of the optimal theory of personal well-being, and surveys the research on the concept and its implications for planning and evaluating services. This article explores the subjective nature of life quality, particularly for people with disabilities, and relates the concept to both cultural norms and universal human values and needs. Each person experiences life, and disability, in unique ways. Practitioners need to consider quality-of-life issues as a context in planning and evaluating quality services. PMID- 8519266 TI - Gifted girls in a rural community: math attitudes and career options. AB - This study was designed to determine the feasibility of improving gifted girls' attitudes toward mathematics. This study was conducted in three school districts in an isolated rural setting. Subjects were 24 gifted girls in Grades 4-7. A control group also contained 24 gifted girls at the same grade levels. On pretest, using the Mathematics Attitude Inventory (MAI), no significant differences were found between groups in their attitudes toward math. The intervention program included problem-solving activities, math-related career options, and self-esteem issues. MAI posttest scores after the 18-week program indicated that the program was effective in changing attitudes toward mathematics of gifted girls in a rural environment. PMID- 8519267 TI - Analysis of science textbook recommendations provided for students with disabilities. AB - Teachers' manuals from three major elementary science textbook series were analyzed. These textbooks provided specific instructional recommendations for students with disabilities in mainstream classes. Findings reveal that (a) the textbooks did not provide recommendations for all categories of disabilities as defined in Public Law 94-142; (b) many recommendations did not specifically address the learning needs of the students for whom they were intended; and (c) there were no consistency in the nature of recommendations provided for any given category of disability. Results indicate that special education and mainstream teachers should monitor the usefulness of published materials that claim to meet the needs of students with disabilities. PMID- 8519268 TI - Categorical and programming changes in special education services. AB - Special education students (N = 654) were studied to determine what proportion had a categorical or programming change and what factors (child, school, and home) were associated with change. The study included all students with disabilities from preschool through secondary school in a tricounty rural district. Data were gathered through a record review and parent survey. Change was found to be more common than is generally perceived: 38.2% of the students had a classification change (21.9% by termination and 16.3% by reclassification). Rates of change varied significantly among classifications and the student's initial classification, grade level, and comorbidity were significantly predictive of change in classification. PMID- 8519269 TI - A comparison of two approaches for teaching complex, authentic mathematics problems to adolescents in remedial math classes. AB - Two groups of adolescents with learning difficulties in mathematics were compared on their ability to generate solutions to a contextualized problem after being taught problem-solving skills under two conditions, one involving standard word problems, the other involving a contextualized problem on videodisc. All problems focused on adding and subtracting fractions in relation to money and linear measurement. Both groups of students improved their performance on solving word problems, but students in the contextualized problem group did significantly better on the contextualized problem posttest and were able to use their skills in two transfer tasks that followed instruction. PMID- 8519270 TI - 20-hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries. AB - Recently we have demonstrated that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20 HETE) constricts rat aortic rings and that this effect is cyclooxygenase- and endothelium-dependent. Incubation of 20-HETE with ram seminal vesicles, a rich source of cyclooxygenase, led to the identification of vasoconstrictor metabolites, the 20-hydroxy-endoperoxides. In the present study, we demonstrated differences in the potency of 20-HETE to constrict several arteries. In all blood vessels tested, the 20-HETE contractile effect was cyclooxygenase- and endothelium-dependent. Differences in contractile potency of 20-HETE varied according to the blood vessels; potency being higher in more muscular arteries than elastic ones. Furthermore, 20-HETE was more potent in eliciting vasoconstriction than its precursor, arachidonic acid. We also provide evidence for the generation of 20-hydroxy-endoperoxides from 20-HETE by the endothelial cyclooxygenase. 20-HETE is a major arachidonate metabolite formed by the cytochrome P450 monooxygenases in rat, human and rabbit kidneys. In addition, blood cells such as leukocytes have the ability to produce 20-HETE, suggesting its presence in the circulation. Furthermore, 20-HETE has been shown to inhibit platelet aggregation. Thus, the ability of 20-HETE to modulate vascular tone and platelet function implicates a role for this compound in the regulation of hemostasis. PMID- 8519271 TI - Handling history of rats modifies behavioural effects of drugs in the elevated plus-maze test of anxiety. AB - In rats naive to handling, but not in handling-habituated animals, baclofen (1 mg/kg) and (R,S) zacopride (1 microgram/kg) had significant anxiolytic effects, shown by an increased percentage of time spent on the open arms of the elevated plus-maze. The effects of buspirone were also modified by the animals' handling history and 200 micrograms/kg was significantly anxiogenic only in handling habituated animals. The pattern of results is discussed in relation to biochemical differences already reported between handling-naive and handling habituated animals, with particular respect to changes in the 5-HT system. PMID- 8519272 TI - Ca2+ channel antagonists and inhibition of protein kinase C each block contraction but not depolarization to 5-hydroxytryptamine in the rabbit basilar artery. AB - The Ca2+ channel antagonists nifedipine and verapamil each significantly inhibited (50-100%) the smooth muscle contraction induced in response to either 5 hydroxytryptamine (1 microM, 5-HT) or 20 mM K+ (K(+)-physiological salt solution) in the basilar artery. Simultaneous measurements of smooth muscle membrane potential showed that changes in potential were not modified at this time. A similar inhibitory action against the smooth muscle contraction but not the depolarization to 5-HT was obtained with the putative protein kinase C and phospholipase C inhibitors, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (10 microM, H7) and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (70 microM, NCDC). These data indicate that 5-HT-induced Ca2+ influx through voltage sensitive channels is important for smooth muscle contraction but not depolarization in the rabbit basilar artery. PMID- 8519273 TI - Capsaicin pretreatment of guinea pigs in vivo prevents ovalbumin-induced tracheal hyperreactivity in vitro. AB - The role of substance P-containing sensory nerves in the development of tracheal hyperreactivity to histamine and arecoline was investigated in an allergic model of asthma. Male Hartley-strain guinea pigs were sensitized to ovalbumin (20 mg/kg i.p.) and 14 days later exposed to either saline or ovalbumin (2%) aerosols for 8 consecutive days. One day after the last aerosol exposure the animals were killed and the tracheas were removed. Isotonic muscle shortening in response to increasing doses of histamine and arecoline was measured. Capsaicin (50 mg/kg s.c.) or vehicle pretreatment was performed 7 days prior to sensitization. Tracheas from vehicle-pretreated sensitized and ovalbumin-aerosol exposed animals had increased reactivity to both histamine and arecoline compared to saline aerosol exposed animals. Capsaicin pretreatment did not alter tracheal reactivity in the saline-aerosol exposed group. Capsaicin pretreatment prevented the increase in tracheal reactivity caused by both agonists in sensitized and ovalbumin-aerosol exposed guinea pigs. These results suggest that capsaicin sensitive sensory nerves are important for the development of increased tracheal reactivity in an allergic model of asthma. PMID- 8519274 TI - Search for an antidote to electroconvulsion and lethality in aminophylline sensitized mice. AB - Diazepam (10 mg/kg i.p.) or MK-801 (0.25 mg/kg i.p.) offered complete protection against corneal electroshock (30 mA x 0.2 s)-induced tonic seizures and lethality but failed to protect from aminophylline (150 mg/kg i.p.) + electroshock (15 mA x 0.2 s)-induced tonic seizures and lethality in mice. The diazepam (2.5 mg/kg i.p.) and MK-801 (0.25 mg/kg i.p.) combination completely protected the mice from aminophylline + electroshock-induced seizures and lethality. Sodium valproate (500 mg/kg i.p.) protected the mice from electroshock (30 mA) per se and aminophylline + electroshock (15 mA)-induced seizure and lethality. The present study established the neurosensitizing potential of a single, non-convulsive dose of aminophylline for electroconvulsion due to subthreshold intensity electroshock and demonstrated the prophylactic efficacy of sodium valproate and the synergistic therapeutic potential of diazepam and MK-801 combination against such seizure attacks. PMID- 8519275 TI - [3H]paroxetine binding and serotonin content of rat brain: absence of changes following antidepressant treatments. AB - The high affinity binding of [3H]paroxetine was measured in rat cerebral cortex following chronic treatment (21 days) with imipramine (5 mg/kg), trimipramine (5 mg/kg) and fluoxetine (2 mg/kg), in adult (3-4 months) or neonatal (7 days of age) rats. Tissue concentrations of serotonin and of its metabolite 5 hydroxyindole-3-acetic acid were also determined by high-performance liquid chromatography in cingulate cerebral cortex, rostral neostriatum, hippocampus and midbrain raphe nucleus region. No differences were found in any of the parameters of [3H]paroxetine binding after antidepressant administration, in either adult or neonatal animals. In addition, endogenous serotonin and 5-hydroxyindole-3-acetic acid levels were not different from control values in any of the regions examined. The present study shows that the serotonin uptake recognition site is resilient to changes after chronic treatment with therapeutic doses of antidepressants, and emphasizes the potential usefulness of uptake site ligands as markers to quantify innervation densities within the brain. PMID- 8519276 TI - Involvement of cholinergic neurons in intestinal contraction caused by vasoactive intestinal contractor. AB - The mechanism of the contractile response to vasoactive intestinal contractor (VIC) was examined in the isolated guinea-pig small intestine. VIC at 10(-9) to 10(-7) M produced a transient relaxation followed by a contraction, and this contraction was partially inhibited, to the same degree, by either atropine or tetrodotoxin. VIC (10(-8) M) induced an increase in the release of [3H]acetylcholine from the ileum preloaded with [3H]choline. The VIC-induced acetylcholine release was dependent on external Ca2+. Thus, the VIC-induced contractions may relate to stimulation of cholinergic neurons and smooth muscle cells. PMID- 8519277 TI - The effect of intrathecal guanfacine and clonidine on the flexor reflex in rats with intact and sectioned sciatic nerves. AB - We examined the effect of intrathecal (i.t.) administration of the non-selective alpha 2-adrenoceptor agonist clonidine and the alpha 2A-adrenoceptor selective agonist guanfacine on flexor reflex excitability in decerebrate, spinalized, unanesthetized rats before and after unilateral section of the sciatic nerve. Both guanfacine and clonidine dose dependently depressed the flexor reflex in rats with intact nerves. There was a dramatic increase in the sensitivity of the flexor reflex to the depressive effect of i.t. clonidine 4 to 18 days after sciatic nerve section. In contrast, the sensitivity to i.t. guanfacine increased only slightly. The present results suggest that the markedly increased sensitivity to the analgesic effect of the non-selective alpha 2-adrenoceptor agonist does not involve up-regulation of alpha 2A-adrenoceptors. Since radioligand binding data suggested that about 4% of spinal cord alpha 2 adrenoceptors are of the alpha 2C type, whereas alpha 2B-adrenoceptors are not detectable, alpha 2C-adrenoceptors seem to be a good candidate to mediate the up regulated response to clonidine in axotomized rats. Thus, alpha 2C-adrenoceptor agonists may be useful in the treatment of neuropathic pain. PMID- 8519278 TI - In vitro binding of a novel dopamine D3 receptor ligand: [125I]trans-7-OH-PIPAT A. AB - An iodinated dopamine D3 receptor ligand, [125I]trans-7-OH-PIPAT-A-trans-7 hydroxy-2-(N-n-propyl-N-3'-iodo-2 '- propenyl)aminotetralin, was developed. This ligand demonstrated unique high affinity and selectivity toward the dopamine D3 receptor; Kd = 0.48 nM and Bmax = 240 fmol/mg of protein in rat striatal membrane homogenates. PMID- 8519279 TI - Involvement of platelet-activating factor in death following anaphylactic shock in boosted and in unboosted mice. AB - The interference of the platelet-activating factor (PAF) receptor antagonist compound, WEB 2170, on death caused by antigen in boosted or unboosted immunized mice was investigated. Death was triggered by the i.v. injection of ovalbumin into animals actively sensitized 14 or 21 days before and that received (boosted) or did not receive (unboosted), a second immunization 14 days later. No significant difference in the response to PAF (50 micrograms/kg) or to ovalbumin (500 micrograms/kg) was noted in boosted or unboosted mice in terms of mortality. WEB 2170 was equieffective to prevent death by PAF in non-sensitized or sensitized boosted or unboosted mice. The i.p. treatment with WEB 2170 (8-16 mg/kg) 1 h before the antigenic challenge prevented death due to antigen in unboosted or in boosted mice. Our results suggest that PAF is involved in the anaphylactic shock in unboosted and boosted mice. In addition, different from the anaphylactic reaction developed in the mouse paw, the participation of PAF in the anaphylactic shock caused by antigen is not dependent on the delivery of a booster injection. PMID- 8519280 TI - Recombinant human type II phospholipase A2 lacks edema producing activity in rat. AB - The rat paw edema-inducing, acute inflammatory activity of four snake venom phospholipase A2S (PLA2) (Naja naja, Naja mocambique mocambique, Crotalus atrox and recombinant Naja naja naja) and of recombinant human type II PLA2 (rh-PLA2) found in rheumatoid synovial fluid, were compared after a bolus subplantar injection. The snake venom-derived PLA2s, including the recombinant Naja naja naja, were potent inducers of paw edema. On the other hand, when given in similar amounts (protein and/or enzymatic activity), the rh-PLA2 did not produce paw edema. Furthermore, the addition of Naja naja PLA2, blood plasma from rats with adjuvant arthritis or the E. coli-based enzymatic incubation mixture used to measure PLA2 activity to the injection mixture containing rh-PLA2, did not result in paw edema-inducing activity. These results suggest that the lack of paw edema inducing activity of rh-PLA2 may be due to significant structural differences between snake venom PLA2s and human PLA2 which allow snake venom PLA2s, but not the human group II PLA2, to express inflammatory activity as measured by paw edema in rat induced by a bolus injection. PMID- 8519281 TI - Mechanisms of action in the liver of crilvastatin, a new hydroxymethylglutaryl coenzyme A reductase inhibitor. AB - Crilvastatin is a drug from the pyrrolidone family that had been shown to induce non-competitive inhibition of rat hydroxymethylglutaryl-coenzyme A reductase activity in vitro. The aim of this study was to evaluate the activity of crilvastatin on the hepatic metabolism of cholesterol in rats. Crilvastatin increased low density lipoprotein (LDL)-cholesterol uptake by the liver more than high density lipoprotein (HDL) uptake, thus increasing by up 30% the clearance of excess plasma cholesterol. In normolipidemic rats, crilvastatin significantly enhanced acyl coenzyme A:cholesterol acyl transferase and cholesterol 7 alpha hydroxylase activity. In rats with a previous high cholesterolemia, crilvastatin also enhanced cholesterol 7 alpha-hydroxylase activity and did not increase liver acyl coenzyme A:cholesterol acyl transferase activity. These findings suggest that a drug such as crilvastatin could have a hypocholesterolemic effect by a mechanism other than the sole inhibition of cholesterol synthesis, possibly by stimulating cholesterol and bile salt secretion via the biliary tract in previously hypercholesterolemic rats. PMID- 8519282 TI - Calcium entry blocking activities of MPC-1304 and of its enantiomers and metabolites. AB - The Ca2+ entry blocking effects of MPC-1304, a new Ca2+ entry blocker of the 1,4 dihydropyridine type, and of its (S) and (R) enantiomers and metabolites were examined on Ca(2+)-induced contractions in isolated rabbit arteries. The Ca2+ entry blocking activity of the (S) enantiomer of MPC-1304 was approximately 150 times greater than that of its (R) enantiomer. Likewise, the antihypertensive effect of the (S) enantiomer was twice as great as that of MPC-1304 (racemate) in conscious spontaneously hypertensive rats, while the (R) enantiomer was ineffective. Thus, most of the pharmacological activity of MPC-1304 resides in its (S) configuration. The main metabolic products of MPC-1304 also inhibited the Ca(2+)-induced contraction in the isolated vascular smooth muscles. These active metabolites showed a stereoselectivity similar to that of MPC-1304 for Ca2+ entry blocking activity, and may contribute to the potent antihypertensive action of MPC-1304. PMID- 8519283 TI - Inhibition of Na+/Ca2+ overload with R 56,865 protects against cardiac arrhythmias elicited by ouabain in vivo in guinea-pigs. AB - Several studies have suggested a central role for Na+/Ca2+ in the pathogenesis of ouabain-induced cardiac arrhythmias. To test this hypothesis, the effects on ouabain-induced arrhythmias of i.v. pretreatment with R 56,865, a Na+ and Ca2+ overload inhibitor, were compared with those of lidocaine, verapamil and tetrodotoxin in anesthetized guinea-pigs. Cardiac arrhythmias were induced by i.v. infusion of ouabain (10 micrograms/kg per min). All nine guinea-pigs pretreated with saline developed ventricular premature beats at an ouabain dose of 159 +/- 9 micrograms/kg (mean +/- S.E.M.), ventricular tachycardia at a dose of 190 +/- 10 micrograms/kg, ventricular fibrillation at a dose of 253 +/- 18 micrograms/kg and died at a dose of 269 +/- 16 micrograms/kg; none of the animals developed heart block or asystole. Pretreatment with R 56,865 (1.25 mg/kg, n = 6) significantly increased the ouabain doses required to induce ventricular premature beats, ventricular tachycardia, ventricular fibrillation and death relative to those for the saline group. Pretreatment with a Ca2+ entry blocker verapamil (0.32 mg/kg, n = 6) also significantly increased the ouabain doses required to provoke ventricular arrhythmias and death; this medication was associated with second or third degree heart block during ouabain infusion in four out of six animals. Pretreatment with lidocaine (10 mg/kg, n = 6) caused a significant increase in the dose of ouabain needed to initiate cardiac arrhythmias and to cause death. Pretreatment with a selective Na+ channel blocker tetrodotoxin (4 micrograms/kg, n = 6) also significantly increased the ouabain doses required to provoke ventricular premature beats, ventricular tachycardia, ventricular fibrillation, and death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519284 TI - Evidence that [Sar1]angiotensin II behaves differently from angiotensin II at angiotensin AT1 receptors in rabbit aorta. AB - Three peptide analogues, [Sar1]angiotensin II, angiotensin II and [Asn1, Val5]angiotensin II, that act at angiotensin AT1 receptors were compared in an isolated rabbit aorta assay. Significant differences have been found among them in agonist profiles and agonist-antagonist interactions with losartan, a nonpeptide antagonist selective for AT1 receptors. Most significantly, underestimation of the antagonist potency for losartan with a flat Schild plot was obtained with [Sar1]angiotensin II. These findings were confirmed in further examinations with representative peptide antagonists including [Sar1,Ala8]angiotensin II. The failure of PD123177, a nonpeptide antagonist selective for AT2 binding sites, to induce any significant difference in the complex antagonism of [Sar1,Phe(Br5)8]angiotensin II to angiotensin II appeared to rule out significant involvement of AT2 binding sites in the differences observed among the agonists, as well as in the complex antagonism. On the basis of the present findings it is speculated that either a saturable agonist removal process or heterogeneous sub-populations of AT1 receptors may be involved. PMID- 8519285 TI - A novel ligand, [125I]BQ-3020, reveals the localization of endothelin ETB receptors. AB - The precise localization of an endothelin (ET) receptor subtype, the ETB receptor, in porcine lung was elucidated by in vitro microautoradiography using a novel ETB-selective radioligand, [125I]BQ-3020 ([125I-Tyr]-N-acetyl-Leu-Met-Asp Lys-Glu-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp -Ile-Ile-Trp). Of the labeled native ET isopeptides, [125I]ET-3 is selective for ETB receptors. However, [125I]ET-3 was not suitable for autoradiography due to its high degree of non-specific binding. On the other hand, [125I]BQ-3020 showed extremely low non-specific binding on autoradiography. The distribution of [125I]BQ-3020 binding in porcine lung was clearly different from that of [125I]ET-1, which showed more widespread binding than [125I]BQ-3020 due to a high affinity to both ETA and ETB receptors. [125I]BQ 3020 was found to bind to parenchyma, parasympathetic ganglia, pulmonary and submucosal plexuses, but bound only slightly to circular smooth muscle layers and the epithelium of airway tracts. Although [125I]ET-1 bound to the smooth muscle layer of all blood vessels, the binding of [125I]BQ-3020 differed among blood vessels. [125I]BQ-3020 binding in blood vessels paralleled acetylcholinesterase activity, suggesting that ETB receptors in blood vessels are located on parasympathetic nerves. Thus, the radioligand [125I]BQ-3020 is very useful for studying the precise localization of ETB receptors. PMID- 8519286 TI - [Comparison of the gold wire electrode with cotton wick electrode for electroretinography in small laboratory animals]. AB - Using the gold wire and cotton wick electrodes, the electroretinograms of mice and rats were measured, and then they were compared. The results obtained were as follows: 1) There were no remarkable differences in the latencies and amplitudes of a- and b-waves, amplitudes and numbers of waves of oscillatories between two different electrodes. 2) It was easy to make and maintain the gold wire electrode as compared with the cotton wick electrode. From these results, it appears that the gold wire electrode is useful for measuring the electroretinogram of small laboratory animals. PMID- 8519287 TI - Reference values for organ weight, hematology and serum chemistry in the female ferret (Mustela putrius furo). AB - Organ Weight, hematologic and blood chemistry values were determined to establish reference values in the female ferret. Organ weight per kg body weight was calculated for various organs. Body surface area (BSA) was also determined by the direct method, and K values (constant) were calculated. The K value was 3.48 in the Dubois and Dubois equation, and 9.69 in the Meeh-Rubner equation. Blood samples were used to record 10 hematologic and 57 serum (plasma) chemistry values, and 7 immunological parameters. Among hematologic values, values whose coefficient of variation (cv) exceeded 30% were RBC, WBC and PLT. In blood chemistry, the CV of gamma-G, UA, ZTT, GPT, gamma-GTP, MAO, ALD and IgG exceeded 30%. In the total amino acid analysis, only the CV of TAU exceeded 30%. Electrophoretograms of amylase and CPK isozyme were quite different from those of humans. Although 1-MEHIS, 3-MEHIS and CAR have not been detected or are present in trace amounts in human plasma, concrete values were detected in female ferret plasma. Hematologic and serum chemistry values were in general agreement with normal values seen in cats and dogs. However, the alpha 1-G percentage, and ALP and amylase activities were lower than the corresponding values in cats and dogs. The RBC count, RET-C percentage and LDH activities were higher than in cats and dogs. Since there have been no comprehensive articles on reference values for the female ferret, the present report contributes to studies that involve this animal as an experimental model. PMID- 8519288 TI - [Hypothalamo-pituitary-ovarian function in female Japanese monkeys (Macaca fuscata) in the non-mating season]. AB - We investigated the mechanism of reduction of hypothalamo-pituitary-ovarian function in female Japanese monkeys in the non-mating season. We administered PMSG and LH-RH to 19 females in the non-mating and in the mating season. When PMSG was administered every day for 12 to 14 days to seven monkeys in the non mating season, follicle development was observed together with an increase in serum estradiol-17 beta (E2), but there was no rise in serum LH in two animals and little increase in five others. Follicle involution began about ten days after PMSG administration, and no ovulation occurred. These findings show that secretion of LH by the pituitary in response to positive feedback by the E2 secreted by the follicles which had developed was in adequate to induce ovulation. Serum LH levels increased markedly in five females after a single iv injection of LH-RH in the mating season, but not at all in the non-mating season, even when five-times the dose was administered. These data show that the LH secreting function of the pituitary is definitely reduced in the non-mating season. When LH-RH was administered to seven monkeys following PMSG administration, an LH surge was observed in all animals, and ovulation occurred in four animals. These findings suggest that one reason for the reduction in pituitary-ovarian function in the non-mating season was a decline in LH-RH secretion by the hypothalamus. PMID- 8519289 TI - [Morphometrical study of physical growth of laboratory-bred cynomolgus monkeys: a longitudinal study during the first 6 years of life]. AB - Physical growth was studied longitudinally in laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged between zero and 6.0 years (females), and between zero and 6.5 years (males). A series of 17 variables representing physical elements were measured in 12 females and 10 males. Rates of increase in morphological total face length and morphological upper face length were somewhat larger than rates of increase in head length and head breadth. Trunk traits showed relatively high growth rates compared to those of leg and arm traits. Growth functions (Gompertz, logistic and quadratic equations) were applied to the growth data. The quadratic equation had the closest fit to the morphometrical growth data in this primate species. PMID- 8519290 TI - Dust inhalation system for small laboratory animals. AB - In order to stabilize the dust concentration for animal inhalation studies, two feedback systems were introduced. Dusts generated were passed through two cyclone separators and stored first in a storage chamber. Then they were aspirated into an ejector by compressed carrier air, mixed with filtered room air in a mixing box, and introduced into an exposure chamber. The first feedback system was for dust generation. Dusts were reaerosolized by on-off control using the output signals from a light-scattering dust detector connected to a storage chamber. The second system was for the control of compressed carrier air flow into an ejector. Compressed air flow was automatically regulated by a PID-controller in combination with a mass flow controller. The PID-controller processed continuous signals from another dust detector connected to an exposure chamber and fed control signals to a mass flow controller for regulation of the compressed air flow. This automatic control system could not only reduce hunchings of dust concentration following on-off control of a dust generator but also reduce overshooting of dust concentration in the exposure chamber following the detachment and dispersion of dusts adhering to the inner walls of the dust supplying route. The system could also maintain a desired dust concentration in the exposure chamber for up to 180 days (20 hr/day, 7 days/week). In addition, this system could simultaneously introduce different doses of dust to other exposure chambers stably while maintaining similar size distribution of the dusts if additional identical exposure units were used. These results indicate that this dust inhalation system is suitable both for long-term studies and for investigating a dose-response relationship. PMID- 8519291 TI - Identification of inbred strains of mice and genetic relationships between strains as assessed by DNA fingerprinting. AB - Strain identification and the assessment of genetic relationships among inbred strains of mice were examined by DNA fingerprinting using M13 phage DNA as a probe. We used 8 inbred strains (NC/Jah, DDD/Jah, DSD/Jah, RR/Jah, SS/Jah, C3H/HeJah, C57BL/6 Jah and C57BL/6CrSlc) and coisogenic (NC-brp) as well as congenic (C57BL/6-bg) strains. DNA fingerprints using M13 phage DNA as a probe revealed identical patterns within strains. Bands due to new mutations in minisatellite regions within each strain were not observed. The banding patterns were strain-specific. Thus, DNA fingerprinting seemed to be suitable for genetic monitoring of mice. A dendrogram constructed with difference values calculated from DNA fingerprint patterns showed that relationships among strains reflected the history of these strains, so DNA fingerprinting could also be effectively used to assess the relationships between inbred strains of mice. PMID- 8519292 TI - [Inbreeding process and establishment of new inbred lines derived from the Japanese house mouse, Mus musculus molossinus]. AB - Inbreeding of 8 groups in molossinus mouse began in (Miura female x Urawa male) F1 (MU) from the stock captured in the Kanto district of Japan and were accomplished by each primiparous littermates. The animals were kept under a clean conventional condition at 23.5 +/- 2.5 degrees C and 50 +/- 5% in relative humidity. Pellet feed, CRF-1, and tap water were provided ad libitum. The respective number of inbreeding generations of MUA, MUF and MUG now exceeds F21, F20 and F22, respectively. Inbreeding of MUD and MUE have reached to F18 up to now, but the other 3 groups became extinct at F10. Time required for inbreeding from F0 to F20 was 2,280 days for MUA, 2,454 days for MUF and 2,143 days for MUG. Generation time was 114.0 +/- 47.2 days for MUA, 122.7 +/- 54.6 days for MUF and 107.2 +/- 48.5 days for MUG. Though the generation time varied from a minimum of 60 days to a maximum of 258 days from F0 to F10 in the inbreeding process (mean: 150.2 +/- 41.7 days), which were shortened from F10 and the mean was 79.0 +/- 29.1 days. In the breeding of the molossinus mouse, primiparous age was 124.5 +/- 29.7 days from F0 to F9 and 77.8 +/- 9.3 days from F10 to F19. The litter size was 5.1 +/- 1.3 for MUA and 5.0 +/- 1.3 for MUG in offspring, 5.0 +/- 1.2 and 4.9 +/- 1.2 in weanling, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519293 TI - [Changes in body weight, food and water intake, organ indices and tissue component parts with growth in the established inbred lines derived from the Japanese house mouse, Mus musculus molossinus]. AB - Changes in body weight, food and water intake, organ indices and tissue component parts with growth in the inbred lines of the molossinus mouse were examined. The characteristic for the mouse is to be very small in body weight; the body weights linearly increased from neonatal period to 1 month and also increased with age, but became constant after 7 months (19.9 +/- 1.6 g) for male and 9 months (19.3 +/- 0.7 g) for female. Maximum body weight was 21.5 g for the male and 20.1 g for the female. Food and water intake per g in body weight rapidly decreased from 1 to 6 months and became constant in the later months and levels of both intakes for females were significantly higher than for males after 6 months. Organ indices (g/body weight) of liver and lung in the later months were higher than in the earlier stage, but heart index was constant in all ages. The curve of splenic index showed an exceptional pattern, in which the lowest level appeared at 3 months. Renal index was larger in the male than in the female, but number of glomerulus in renal cortex was significantly greater in the female more than in the male at all ages. Testicular index increased until 3 months and decreased in the later stage, and the percent of seminiferous epithelium was larger at 3 months than at the other ages. Thymic index successively decreased with age; the occupied area of the cortex declined, but conversely the connective tissue and fat increased with thymic involution. PMID- 8519294 TI - [The effect of four recipient strains on intra-uterine growth in mice--birth weight]. AB - The embryo transfer technique is a very powerful tool for detecting intra-uterine effects of dams on prenatal growth of embryos. Embryos of DDD strain were transferred to a recipient of the same strain. Litter size, gestation period and birth weight of newborn offspring were measured. To examine the effect of embryo transfer on the prenatal growth of embryos, these results were compared with those of newborn DDD strain of mice that had developed from non-transferred embryos. Embryos of DDD strain were transferred to four strains of recipients (DDD/Qdj, C3H/Qdj, C57BL/Qdj and DBA/1J Sea). Litter size, gestation period and birth weight of newborn offspring were measured. The four strains of recipients were compared to examine the effect of recipient strain on the prenatal growth of the embryos. The results were as follows. 1. There was no gender difference in birth weight of offspring. 2. A negative correlation (partial regression coefficients: -0.024, P < 0.001 in the transfer and non-transfer groups, and 0.058, P < 0.001, in the four strains of recipients) was observed between litter size and birth weight of newborn offspring, while a positive correlation (partial regression coefficients: 0.068, P < 0.001 in the transfer and non-transfer groups, and 0.071, P < 0.001 in the four strains of recipients) was observed between gestation period and birth weight of newborn offspring. 3. Embryo transfer might affect the intra-uterine growth of transferred embryos. 4. The four different strains of recipients might contribute unequally to the prenatal growth of transferred embryos because of their different intra-uterine conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519295 TI - Early hepatic lesions with marked glandular structures induced in rats by 0.1% ethionine in a choline deficient diet. AB - Early hepatic lesions in rats fed ethionine plus a choline deficient (ECD) diet were examined histopathologically. The purpose of this experiment was to examine preventive and suppressive effects of drugs on fatty or cirrhotic liver induced by ECD, but contrary to our expectations, all groups except the normal diet group showed neoplastic lesions in the liver. Macroscopically, milky-white nodules were seen in most all the rats except for a few dead ones. Microscopically, the characteristic lesions consisted of neoplastic nodules, glandular structures and oval cell hyperplasia. The glandular structures were already present in a rat that died on day 34 of administration and showed neoplastic developmental structures morphologically similar to cholangiofibroma. The neoplastic nodules appeared later than the glandules and were observed in rats that died after day 42. To the best of our knowledge, this is the first report of hepatic lesions consisting of mainly glandular structures induced by an ECD diet. PMID- 8519296 TI - [Study on the glomerular foam cells in stroke-prone SHR]. AB - Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9 month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation. PMID- 8519297 TI - Pituitary and serum levels of prolactin (PRL), thyroid stimulating hormone (TSH) and serum thyroxine (T4) in hereditary dwarf rats (rdw/rdw). AB - Female and male hereditary dwarf mutation rats (rdw), offspring of those found by Koto et al. in a breeding colony of Wistar-Imamichi rats, were decapitated to collect blood and pituitary glands at 10 weeks of age. Levels of pituitary prolactin (PRL), thyroid stimulating hormone (TSH) and serum PRL, TSH and thyroxine (T4) in rdw rats were measured and compared with levels in normal rats (N). The hormone levels were measured with radioimmunoassay (RIA). It was found that the levels of pituitary and serum PRL were considerably lower in rdw rats and that the level of serum T4 was also significantly lower than that in normal rats. TSH per pituitary was significantly lower in rdw rats but TSH per mg pituitary was not different between rdw and normal rats. The levels of serum TSH in rdw was not different from that in normal rats, but was rather higher in female rdw rats than in normal female rats. When the results of previous research were combined with the present results, it was clear that rdw rats are characterized by hypoplasia of GH and PRL synthetic cells of the pituitary and that rdw rat is possibly useful as a model animal with endocrinological defects in pituitary PRL and GH. PMID- 8519298 TI - Usefulness of a simplified artificial insemination technique in the rabbit for teratology studies. AB - We describe usefulness of our simplified artificial insemination technique in rabbits for teratology studies. Our technique includes 1) semen collection from 2 or 3 bucks with a simple artificial vagina, 2) deposition of 0.5 microliters of the diluted semen mixture in the vagina with a glass pipette, and 3) injection of 25 U. of hCG through the auricular vein. Applying these techniques and procedures and keeping about 10 proven bucks would enable 2 operators to inseminate 10-15 does daily by only 1 hour work. This artificial insemination technique should be useful for rabbit teratology studies, especially for safety evaluation studies of toxicants, where a relatively large number of pregnant are needed to be prepared in a short period. PMID- 8519299 TI - Emetic responses of Sorex unguiculatus. AB - We have shown previously that Suncus murinus, a species of the insectivore, can vomit in response to various emetogenic stimuli. In the present study we investigated whether or not Sorex unguiculatus, which belongs to different subfamily (Soricinae) of insectivore, vomits in response to emetogenic drugs. Subcutaneous injection of veratrine and oral administration of copper sulfate caused emesis in the animal. Histological study showed that bilateral structure of the area postrema was not important for the emetic reflex. Therefore, the capability of emesis may be common to the family of soricidae of the insectivore, and the Sorex unguiculatus is the smallest known mammal which can vomit. PMID- 8519300 TI - Survival of mouse morulae and blastocysts derived from in vitro fertilization after ultra rapid freezing. AB - Mouse morulae and blastocysts derived from in vitro fertilization were placed in a highly concentrated vitrification solution (DAP 213:2 M dimethyl sulfoxide, 1 M acetamide, 3 M propylene glycol in PB 1) in a sampling tube at room temperature, plunged into liquid nitrogen within ten seconds and cryopreserved. Thawing was carried out by directly pouring 37 degrees C 0.3 M sucrose solution into the sampling tube. The ratios of morphologically normal embryos at the morula and blastocyst stages after thawing were 92.0% (149/162) and 13.3% (13/98), respectively. The rate of development from morphologically normal morulae into blastocysts in vitro was 83.1% (74/89). Some of the morphologically normal morulae were transferred to pseudopregnant recipients immediately after thawing, and 45.0% (27/60) of the embryos developed into normal young. PMID- 8519301 TI - [Investigation of repeated marrow sampling from dogs]. AB - In order to apply a marrow aspiration technique to the safety study employing dog, a series of 4 marrow aspirations from the sternum of Beagle dog at intervals of 30 days were performed. No remarkable changes were observed in general conditions, body weight, body temperature, hematology and bone marrow differential cell counts. Except a temporal increase of CPK activity at day 1, no significant changes were also observed in serum biochemical analysis. PMID- 8519302 TI - [Adrenocortical zonation in human growth hormone gene (hGH) transgenic mice]. AB - Adrenocortical zonation was histologically examined in 2 infertile female transgenic (Tg) mice which carried human growth hormone (hGH) gene and had a high circulating level of hGH. The adrenal cortices of Tg mice were characterized by the appearance of hypertrophied zona fasciculata cells with the cytoplasm filled with many lipid droplets even in size, the absence of the distinctive z. reticularis and the persistence of the X zone with nodules in one and without them in the other. The last finding might be explained by the reflection of the strain differences used in Tg mouse construction. It was, however, suggested that the X zone degeneration might not be associated with the adenohypophysis. The changes observed in z. fasciculata cells were interpreted as the effects of ACTH like function of circulating hGH in addition to the known PRL-like function. The absence of the z. reticularis may be explained by its morphological similarity to z. fasciculata under the effects of the circulating hGH at a high level. In addition to genetic analysis of various inbred strains, Tg mice with ectopic hGH production provide a new methodology in analyzing the mechanism of adrenocortical zone formation. PMID- 8519303 TI - Effects of environmental temperature on atrial natriuretic peptide (ANP)-granules of auricular cardiocytes and plasma ANP level in pregnant rats. AB - The atrial natriuretic peptide (ANP) levels of auricular cardiocytes and plasma were examined by immunohistochemistry, ultrastructural morphometry, and radioimmunoassay (RIA) in pregnant rats (4th, 12th, 20th day of gestation) under 22 degrees C and 33 degrees C environmental conditions. Immunohistochemically, ANP immunoreactivity was stronger on the 20th day of gestation in the 22 degrees C environmental groups, but weaker on the 12th and 20th days of gestation in the 33 degrees C environmental groups. According to the results of ultrastructural morphometry, the number of ANP-granules had increased significantly by the 20th day of gestation in the 22 degrees C environmental groups, but was decreased on the 12th and 20th days of gestation in the 33 degrees C environmental groups. RIA demonstrated that the maternal plasma ANP concentration decreased gradually during pregnancy in the 22 degrees C environment. The plasma ANP concentration in the 33 degrees C environmental groups tended to be lower than that at the same stage of pregnancy in the 22 degrees C environmental groups. PMID- 8519304 TI - Retinal dopamine and its metabolite contents in zitter rats and spontaneously epileptic rats. AB - In order to investigate the relationship between visual dysfunction and retinal DA metabolism in zitter rats and spontaneously epileptic rats (SER), we measured the amounts of retinal dopamine (DA) and its metabolites, 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillate (HVA). DA, DOPAC and HVA contents were markedly decreased in zitter rats as compared with the controls, Kyo:Wistar or Sprague-Dawley rats. In contrast, in SER, retinal DA and its metabolite contents were not significantly different from those of Kyo:Wistar rats. SER showed higher levels of DA and its metabolites in comparison with Sprague-Dawley rats. Thus, it is suggested that the debilitation of retinal DA synthesis is at least partly related to the visual dysfunction observed in zitter rats, but not that of SER. PMID- 8519305 TI - [Adrenocortical zonation in the laboratory Japanese field vole (Microtus montebelli)]. AB - Adrenocortical zonation in the laboratory Japanese field vole (Microtus montebelli) was investigated histologically with special attention to the sex and species specific differences. The whole cortex and zona reticularis showed clear sex differences. They were thicker in females than in males. In this respect the vole was similar to the mouse and rat, but different from the Syrian hamster and mastomys. Male cortices were characterized by thick z. fasciculata and meagre z. reticularis, while both zones were thick in females. The z. fasciculata in both sexes and z. reticularis in females seemed to be divided into two sublayers by the cellular arrangement. No distinctive additional zones were identified. The histological observations indicated that the Japanese field vole might have interesting endocrinological characteristics and serve for studying the mechanism of the zone formation in the mammalian adrenal cortex. PMID- 8519306 TI - [Fertility of male Syrian hamsters paired with one, two and four proestrous females each]. AB - In order to improve the productivity of Syrian hamsters, we investigated whether a male could impregnate overnight more than one proestrous female. Twenty-one males and 49 females aged 8 to 10 weeks were used in this experiment. The mating systems were as follows: one male was paired with one female, one male was paired with two females, and one male was paired with four females. Six out of 7, 7 of 14 and 4 of 28 females became pregnant and gave birth under these three systems, respectively. We conclude that it is possible for a male to impregnate overnight about one female under the above mating systems. PMID- 8519307 TI - Copulatory behavior of sexually inexperienced male guinea pigs paired with synchronized estrus females. AB - The copulatory behavior in sexually inexperienced male guinea pigs aged 12 weeks was observed under dim red illumination. The synchronized estrus females, which were used for receptive females, received a subcutaneous implantation of progesterone-filled tubing for 2 weeks, followed by 0.5mg progesterone injection. Females given these treatment exhibited the lordosis behavior at 19:00 and 21:00 h on 4th day, and had ovulated by 09:00 h on 5th day after removal of implant. During a 2-hrs test session, standard measures of copulatory behavior were recorded. The ejaculation could be observed within the first 30 min in 6 of 7 males. The mounts, intromissions and ejaculation in male guinea pigs were shown in a lower frequency and longer latency than those of rats and hamsters. PMID- 8519308 TI - Molecular epidemiology of Pseudomonas aeruginosa in an intensive care unit. AB - Genotyping was used to analyse Pseudomonas aeruginosa isolates from sink drains and 15 intubated patients as part of a 3-month prospective study of strain transmission in a medical-surgical intensive care unit. Ninety percent of all washbasin drains were persistently contaminated with several P. aeruginosa genotypes. In 60% (9/15) of the patients, P. aeruginosa colonization or infection was hospital-acquired: P. aeruginosa strains isolated from these patients were present in hospital sinks or in other patients before their admission. Since all patients were immobile, personnel were the probable route of transmission of P. aeruginosa in the hospital. The mechanism of strain transmission from sinks to hands during hand washing was investigated in a children's hospital. When P. aeruginosa was present at densities of > 10(5)/c.f.u. per ml in sink drains, hand washing resulted in hand contamination with P. aeruginosa via aerosol generation in the majority of experiments or P. aeruginosa was detected using an air sampler above the washing basin. High P. aeruginosa cfu were present at 4.30 h in the eight sinks (5.4 x 10(5)-7.0 x 10(10) c.f.u./ml), whereas at 13.00 h P. aeruginosa c.f.u. were significantly lower (3.1 x 10(2)-8.0 x 10(5) c.f.u./ml). These data reveal that the danger of bacterial contamination of hands during hand washing is highest in the morning. The identified transmission routes demand more effective hygienic measures in hospital settings particularly concerning personnel hands and sink drains. PMID- 8519309 TI - Molecular studies of plasmids of multiply-resistant Shigella spp. in Hong Kong. AB - One hundred and two Shigella spp. isolated in two hospitals in Hong Kong were analysed for antibiotic resistances, resistance plasmids and plasmid profiles. Three quarters of the isolates were S. flexneri. All isolates harboured plasmids, up to a maximum of ten within one strain. Plasmids of 220 kb encoding resistances to tetracycline, chloramphenicol and sulphonamide and probably also associated with invasiveness in the Sereny test were found in 80 strains and were transferable in 18% of cases. Resistance plasmids of 92 and 99 kb were found in 27 and 15 strains respectively and encoded resistances to ampicillin, tetracycline, chloramphenicol, kanamycin, sulphonamide, trimethoprim, cotrimoxazole and gentamicin; these plasmids were usually transferable. Four plasmids of 3.9, 2.8, 2.2 and 1.8 kb were commonly found in S. flexneri strains, but were rare in other species. In contrast, there was no predominant plasmid profile in S. sonnei. S. flexneri is endemic in Hong Kong and these plasmid studies suggest that the strains in circulation are derived from only a few clones. PMID- 8519310 TI - The prevalence and genetics of resistance to commonly used antimicrobial agents in faecal Enterobacteriaceae from children in Bangladesh. AB - The present study was undertaken to investigate the occurrence of antibiotic resistance in enteric flora in 64 children in rural Bangladesh over a 12-month period. The antibiotic resistance pattern of the isolates varied throughout the year and multiple resistance was highest during the post monsoon period. Seventy three percent of children had isolates resistant to more than three antibiotics throughout the year. Resistance to streptomycin was highest (78%), followed closely by ampicillin (72%). Of 82 multiply resistant isolates, plasmid DNA was demonstrated in 75%. Plasmid sizes ranged between 3.7 and 110 MDa, the commonest plasmids were of 70, 98 and 110 MDa. Complete or partial resistance was transferred by conjugation from 52% of the isolates, most frequently by single plasmids. The commonest plasmid incompatibility group was F11-A (46%) followed by incompatibility group P (22%). Plasmids of molecular weight 98 MDa most often hybridized with F11-A probes and those of 110 MDa with H11 probes. Plasmids from 10 transconjugants were digested with restriction enzymes and digest patterns demonstrated the presence of common plasmids. The findings show that there is a diverse, and mobile, genetic pool of resistance genes in this rural community. This genetic reservoir is potentially transferable to enteric pathogens, with major implications for public health and diarrhoeal disease control. PMID- 8519311 TI - Occurrence of FIme plasmids in multiply antimicrobial-resistant Escherichia coli isolated from urinary tract infection. AB - Plasmids belonging to the FIme incompatibility group were found in seven different serogroups of multiply antimicrobial-resistant Escherichia coli isolated from patients with urinary tract infection (UTI) and living in south east London. Although widespread in Salmonella spp., FIme plasmids have only previously been described in E. coli in a strain of serogroup O15 K52 H1 responsible for an extensive and protracted outbreak of invasive community acquired infection in south-east London in 1986. Our findings suggest either a wider background occurrence of FIme plasmids in E. coli associated with UTI than previously reported or alternatively, the dissemination and subsequent molecular diversification of the FIme plasmid associated with the epidemic strain of serogroup O15 K52 H1. PMID- 8519312 TI - Phage typing of Vero cytotoxin-producing Escherichia coli O 157 isolated in the United Kingdom: 1989-91. AB - Between 1989 and 1991 a total of 1092 Vero cytotoxin-producing Escherichia coli O 157 isolated in the United Kingdom were phage typed in the Laboratory of Enteric Pathogens (LEP). Twenty-three phage types was identified, the most frequent being types 2 (36.1%), 49 (29.6%), 1 (10.3%) and 4 (8.9%). Although isolations of O 157 VTEC have increased each year from 1 in 1982 to 532 in 1991, the predominant phage types have remained unchanged although the proportion of strains belonging to types 2 and 49 has increased. O 157 VTEC from 17 outbreaks were phage typed during this period with phage type 49 predominating (7 of 17 outbreaks). PMID- 8519313 TI - Enterotoxins and toxic-shock syndrome toxin-1 in non-enteric staphylococcal disease. AB - Over the 7 years 1985-91, 997 strains of Staphylococcus aureus from 962 patients with diseases other than food poisoning have been tested for the production of enterotoxins and toxic shock syndrome toxin-1 (TSST-1) and phage typed. In all, 128 cases could be classified as confirmed or probable toxic shock syndrome (TSS) but a further 199 cases were classified as possible or unconfirmed TSS. In 219 cases, an alternative diagnosis could be supported and 45 cases were classified as sudden infant death syndrome. In 371 cases, insufficient information for classification was available. Strains of phage group I producing TSST-1 were associated with menstrual TSS. Many menstrual TSS cases were aged less than 20 and were using non-introducer tampons. When all strains were reviewed, strong associations were observed between TSST-1 production and phage group I strains, enterotoxin B production and group V strains, enterotoxin C and phage-type 95 strains and between enterotoxin A without TSST-1 and phage group III strains. PMID- 8519314 TI - Corresponding type-specificity of vibriocidal and agglutinating activities of Vibrio cholerae antisera: relevance to vaccine immunogenicity. AB - Cholera vibrios can be allocated to one of three biotypes (classical, intermediate and El Tor), each of which can be sub-divided into two serotypes (Ogawa and Inaba). Vibriocidal tests with absorbed antisera have shown no evidence of biotype specificity in the killing of bacteria, but they have confirmed the role of the two serotype-specific antigens in immunity to cholera. The same presence of serotype specificity, and absence of biotype specificity, has been found by bacterial agglutination, an easier and quicker serological test. The use of this simpler test in ensuring a balanced serotype response to cholera vaccine is discussed, together with evidence that may lead to the production of more effective vaccine and better immunity. PMID- 8519315 TI - Pathogenicity of Fusobacterium necrophorum strains from man and animals. AB - Necrobacillosis occurs in man and animals. The typical forms of the disease in animals are caused by Fusobacterium necrophorum biovar A; biovar B strains are much less pathogenic. In this study the pathogenicity for mice of eight human isolates of F. necrophorum was compared with that of animal biovar A and B strains. By subcutaneous inoculation seven of the human strains differed from biovar A but resembled biovar B in (1) producing, at the most, mild local lesions that rapidly healed, and (2) showing no enhancement of infectivity when suspended in sub-lethal doses of Staphylococcus aureus broth culture. The eighth human strain (A2433) resembled biovar A but differed from biovar B in (1) producing severe lesions, and (2) showing greatly enhanced infectivity in the presence of S. aureus. Nonetheless, strain A2433 differed from biovar A, both in the nature of the lesions produced and in its failure to cause severe general signs of illness and rapidly fatal infection. By intravenous inoculation one of two biovar B strains and all except one of the eight human strains produced purulent lesions, often severe, in the liver and elsewhere, but infection was not usually associated with general signs of illness. In contrast, intravenous injection of a biovar A strain gave rise to a rapidly fatal infection, with severe lesions in the liver or elsewhere. The results suggest that the term 'necrobacillosis' as used in human and veterinary medicine refers to diseases that differ in important respects. PMID- 8519316 TI - Factors enhancing adherence of toxigenic Staphylococcus aureus to epithelial cells and their possible role in sudden infant death syndrome. AB - Toxigenic strains of Staphylococcus aureus have been suggested to play a role in sudden infant death syndrome (SIDS). In this study we examined two factors that might enhance binding of toxigenic staphylococci to epithelial cells of infants in the age range in which cot deaths are prevalent: expression of the Lewis(a) antigen and infection with respiratory syncytial virus (RSV). By flow cytometry we demonstrated that binding of three toxigenic strains of S. aureus to cells from nonsecretors was significantly greater than to cells of secretors. Pre treatment of epithelial cells with monoclonal anti-Lewis(a) or anti-type-1 precursor significantly reduced bacterial binding (P < 0.01); however, attachment of the bacteria correlated only with the amount of Lewis(a) antigen detected on the cells (P < 0.01). HEp-2 cells infected with RSV bound significantly more bacteria than uninfected cells. These findings are discussed in context of factors previously associated with SIDS (mother's smoking, bottle feeding and the prone sleeping position) and a hypothesis proposed to explain some cases of SIDS. PMID- 8519317 TI - Staphylococcal food poisoning in the United Kingdom, 1969-90. AB - Between 1969 and 1990 strains of Staphylococcus aureus from 359 outbreaks and sporadic cases of staphylococcal food poisoning in the United Kingdom were examined in the PHLS Food Hygiene Laboratory for the production of enterotoxin. In a number of instances the incriminated foods were also examined for the presence of enterotoxin. Strains from 79% of incidents produced enterotoxin A alone or together with another enterotoxin. The level of S. aureus present in the foods ranged from no viable S. aureus detected to 1.5 x 10(10) c.f.u./g with a median of 3.0 x 10(7) c.f.u./g. Enterotoxin was detected in foods in the absence of viable S. aureus in only two outbreaks and in both cheese was the implicated food. Meat, poultry or their products were the vehicle in 75% of incidents with ham and chicken most frequently implicated. Other foods included fish and shellfish (7%) and milk and milk products (8%). Most contamination took place in the home followed by restaurants and shops. Seventy-one percent of the incident strains were lysed by phages of group III or I/III. PMID- 8519318 TI - Hospital infections in Spain. I. Staphylococcus aureus (1978-91). AB - This study was undertaken to determine the distribution of phage types of Staphylococcus aureus isolates from hospital outbreaks or sporadic cases received in our laboratory during the past 14 years. The records for 15,803 isolates from 55 Spanish hospitals have been analysed. In relation to sporadic isolates we have been able to detect the predominance of phage group I and non-typable staphylococcal strains. Since 1989, we have observed a considerable increase in hospital infection caused by methicillin-resistant S. aureus strains which we could differentiate in to two groups; one belonging to phage group III (6/47/54/75/77/84/85) and other groups of nontypable strains which could be classified as phage group I-III after heat treatment (29/77/84) and with similar patterns by reverse typing (6/47/53/54/75/83A/84/85/W57/1030/18042). During 1990 and 1991, these strains have extended widely to at least six different autonomous regions creating an epidemic situation in Spain. PMID- 8519319 TI - The contamination of pate by Listeria monocytogenes in England and Wales in 1989 and 1990. AB - In July 1989, 1834 samples of pate (of which 1698 were from retail displays) were examined by the PHLS for the presence of Listeria monocytogenes. The survey was repeated in July 1990, when 626 pate samples on retail sale were examined. Between the two surveys there was a marked reduction in the proportions of pates contaminated (10% in 1989 and 4% in 1990) and in the numbers of samples from which > 10(3) L. monocytogenes/g were recovered. The higher rate of contamination detected in 1989 was largely due to pate from a single manufacturer. In both surveys, pate sold as loose slices had higher rates of contamination than those prepackaged. Temperature control had improved between the two surveys where 65% of samples in 1989 and 83% in 1990 were stored at < or = 7 degrees C. Although contamination occurred at almost all temperatures, L. monocytogenes was both quantitatively and qualitatively more common in samples stored at > 7 degrees C. The majority of pates had unexpired shelf lives of between 0 and 3 weeks. Although contamination occurred throughout the shelf life of these products, the proportion of samples where L. monocytogenes was recovered was higher in pates with expired sell by dates. There was an association between high total viable counts and the presence of L. monocytogenes. Likely routes of contamination of pate together with possible preventive measured are discussed. PMID- 8519320 TI - Epidemiology of Salmonella typhimurium: ribosomal DNA analysis of strains from human and animal sources. AB - Salmonella typhimurium is the most frequently identified serovar of Salmonella in Italy. This serovar is characterized by the widespread dissemination among human and non-human sources of phenotypically and genetically well-differentiated clones. In this study 457 strains of S. typhimurium isolated in Italy in the years 1982-91 from human and animal sources were submitted to characterization by the rDNA fingerprinting technique. Application of this typing method, after digestion of chromosomal DNA with HincII endonuclease, confirmed the greatest genetic differentiation of clones of S. typhimurium, allowing reliable identification of 45 rDNA patterns linked into 9 major clusters. rDNA pattern clusters or ribotypes specific to man were not recognized, whereas some rDNA patterns were characteristically related to ducks, pigeons and pet birds. The ribotyping results for isolates from animal hosts suggest that pig and cattle are the main source of human infection. PMID- 8519321 TI - Campylobacter bacteraemia in England and Wales, 1981-91. AB - Routine surveillance of infection in England and Wales detected 394 cases of campylobacter bacteraemia in 11 years. This represented an average incidence of 1.5 per 1000 intestinal campylobacter infections, with a range of 0.3/1000 in children aged 1-4 years to 5.9/1000 in patients aged 65 years or more. Definitive identification of 257 isolates showed that 89% were Campylobacter jejuni or C. coli; other species were C. fetus (8.6%), C. lari (0.8%), C. upsaliensis (0.8%), Helicobacter (Campylobacter) fennelliae (0.8%), and Helicobacter (Campylobacter) cinaedi (0.4%). Most (71%) of the C. jejuni/C. coli bacteraemias were in patients with acute enteritis. Of the patients with C. fetus bacteraemia only 27% had diarrhoea; they were older than patients with C. jejuni or C. coli bacteraemia (54.1 v. 45.9 years) and proportionally more of them were male (M:F ratio 2.7:1 v. 1.9:1); 41% had endovascular pathology or cellulitis. There was a higher proportion of C. jejuni serogroup O 4 (Penner) and O 18 strains among blood than faecal isolates, which suggests that they were unusually serum resistant and/or invasive. PMID- 8519322 TI - Genetic analysis of Escherichia coli from porcine postweaning diarrhoea. AB - A total of 79 Australian isolates of beta-haemolytic Escherichia coli from cases of porcine postweaning diarrhoea (PWD), and 18 isolates of serotype O 149:K91:K88 (F4) from unweaned pigs from Australia, Indonesia and Denmark, were examined by multilocus enzyme electrophoresis. These were divided into 57 electrophoretic types (ETs), with an overall mean genetic diversity per enzyme locus of 0.466. This value closely resembled that previously recorded for the whole species. Not only was the collection diverse, but there was considerable genetic heterogeneity amongst PWD isolates of the same serogroup. Isolates from serogroups O 8 and O 138 were most varied, whilst many from serogroups O 141 and O 149 were more closely related. In contrast, the isolates from the unweaned pigs all belonged to only one ET. PMID- 8519323 TI - Dose-response in an outbreak of non-bacterial food poisoning traced to a mixed seafood cocktail. AB - An outbreak of non-bacterial food poisoning presumed due to small round, structured viruses (SRSV) occurred at a national conference. A detailed postal survey of all conference attenders was carried out to ascertain the cause of the outbreak and 355 questionnaires were returned. Univariate analysis showed that mussels in the seafood cocktail were the likely vehicle of infection. A dose response relationship between the amount of seafood cocktail consumed and the risk of illness was demonstrated. Dose-response has not previously been documented in a food-borne outbreak due to small round structured virus. Detailed quantitative food histories can be useful in eliciting dose-response relationships and may be crucial in establishing the vehicle of infection when investigating food poisoning following consumption of a set-menu meal. Their use should be considered in other outbreak situations. PMID- 8519324 TI - Vero cytotoxin-producing Escherichia coli, particularly serogroup O 157, associated with human infections in the United Kingdom: 1989-91. AB - This survey reports the results of investigations performed by the Laboratory of Enteric Pathogens (LEP), to identify evidence of human infection with Vero cytotoxin-producing Escherichia coli (VTEC) in the UK during the period 1989-91. Bacterial isolates, faecal specimens and serum samples were received from patients suffering from diarrhoea, bloody diarrhoea and haemolytic uraemic syndrome. Using serotyping, Vero cytotoxin gene probing and an ELISA for serum antibodies to E. coli O 157, evidence of infection was detected in 232, 428 and 615 individuals in 1989, 1990 and 1991 respectively. Of these individuals, 15% were reported as having HUS. Vero cytotoxin-producing E. coli O 157 was the most frequently encountered serogroup, with isolations from a total of 1092 individuals over the 3-year period. The incidence of VTEC infection increased from 0.41/100,000 in 1989 to 1.07/100,000 in 1991. The area with the highest rate of infection in each year was Scotland, increasing from 1.37/100,000 in 1989 to 3.97/100,000 in 1991. PMID- 8519325 TI - The colonization of broiler chickens with Campylobacter jejuni: some epidemiological investigations. AB - Between June 1990 and July 1991, broiler chickens from 49 flocks from 23 farms were examined for the carriage of Campylobacter jejuni at slaughter. Thirty-seven flocks (76%) were campylobacter-positive. Prevalence of campylobacter colonization was not associated with any of a variety of factors such as water source and broiler house floor structure. There was also no apparent seasonal variation in carriage. Investigations on one farm indicated that dipping boots in disinfectant before workers entered broiler houses either delayed or prevented colonization with C. jejuni. PMID- 8519326 TI - A bacteriological survey of tuberculosis due to the human tubercle bacillus (Mycobacterium tuberculosis) in south-east England: 1984-91. AB - The occurrence and nature of bacteriologically confirmed tuberculosis due to Mycobacterium tuberculosis in South-East England in the period 1984-91 is reported and compared with the results of a study for 1977-83. Registered new cases reached a low of 1028 in 1988 but increased to 1252 in 1991. This appeared to be due to a halt in the previous decline in new cases of European patients, a small increase in the number of Indian subcontinent (ISC) patients and an increase in patients from Africa. A total of 122 patients, mostly of European ethnic origin, were known to be HIV positive. As in the 1977-83 study, disease in the ISC group affected younger patients than in the European group, tubercle bacilli were more frequently isolated from a non-pulmonary site in the ISC group (45%) than in the European group (19%) and there was a higher incidence of the South Indian variant of M. tuberculosis in the former group (17%) than in the latter (9%). The overall incidence of drug resistance has not altered significantly since the 1977-83 study but 46 strains resistant to 3 or more drugs were isolated from 4099 ISC patients, compared with 3 of 4594 strains from European patients. Six of the 122 isolates from HIV positive patients were drug resistant but none was multi-drug resistant. The slight rise in registered bacteriologically proven cases of tuberculosis, the presence of multi-drug resistant strains, the occurrence of HIV-related tuberculosis and reports of the emergence of multi-drug-resistant HIV-related tuberculosis in other countries strongly indicate the need for continued careful surveillance. PMID- 8519327 TI - Oropharyngeal production of pneumococcal capsular antigen and the potential for contamination of expectorated sputum samples in pneumococcal pneumonia. AB - The presence of pneumococcal capsular antigen (PCA) in the oropharynx was sought in subjects without respiratory tract infection. Saliva specimens from 239 subjects were analysed by counter-current immunoelectrophoresis using 'Omniserum'. 15.5% gave positive reactions but only 24% of positive samples were typable and therefore due to pneumococcal or pneumococcal-like antigens. Given that oropharyngeal production of antigens occurs we investigated whether PCA in expectorated sputum arose from oropharyngeal contamination. Sixteen patients with pneumococcal pneumonia, and with sputum positive for PCA, were investigated in detail. On the basis of serotyping and concentration the PCA in sputum was thought to arise from the lower respiratory tract in all cases. This was confirmed by a simple, novel approach involving the comparison of concentrations in concomitant samples of saliva and sputum. Thus while oropharyngeal production of antigens poses a potential diagnostic problem the latter approach can be used to exclude contamination. PMID- 8519328 TI - Arcobacter cryaerophilus and thermophilic campylobacters in a sewage treatment plant in Italy: two secondary treatments compared. AB - Microaerophilic organisms were monitored in sewage effluent undergoing two secondary treatments: air and oxygen-activated sludge. The mean numbers of Arcobacter cryaerophilus and thermophilic campylobacters detected in incoming sewage were 5639/100 ml and 1720/100 ml respectively. Secondary treatment in air tanks reduced the population of A. cryaerophilus by 97.1% and of thermophilic campylobacters by 99.08%, whereas treatment in oxygen tanks reduced the bacteria 97.8% and 99.63% respectively, showing that oxygen-activated sludge treatment was more effective. Subsequent tertiary treatment with 2 p.p.m. chlorine dioxide evidenced the removal of A. cryaerophilus to 99.9% and eliminated thermophilic campylobacters. Campylobacter jejuni and C. coli constituted 54.1% and 45.9% of 74 thermophilic campylobacter strains isolated. In air-activated sludge effluent C. jejuni was found more often, thus appearing more sensitive to oxygen. The most probable number assay used for detection of campylobacters, blood medium for enrichment and blood-free medium for plating, also appeared to be fit for A. cryaerophilus, the high density of which in urban sewage may be due to inflows from slaughterhouses. PMID- 8519329 TI - Occurrence of Giardia sp. cysts and Cryptosporidium sp. oocysts in faeces from public parks in the west of Scotland. AB - One hundred faecal specimens, randomly collected from various locations within seven public parks in the west of Scotland, were examined for the presence of Giardia sp. cysts and Cryptosporidium sp. oocysts. Eleven percent of samples contained Giardia sp. cysts and 1% contained Cryptosporidium sp. oocysts. Occurrence data from individual parks varied from 0 to 40% for Giardia and 0 to 2.4% for Cryptosporidium. The occurrence of parasitic organisms in public parks, especially in the vicinity of children's playing areas is a matter of concern for public health officials and regulators of leisure and recreation amenities. PMID- 8519330 TI - Serological diagnosis of leishmaniasis: on detecting infection as well as disease. AB - Serological tests are very frequently used in epidemiological surveys of leishmaniasis and other parasitoses. Their sensitivity and specificity are generally defined with respect to parasitism and disease, rather than infection. The reason is that known positives are those individuals most likely to yield parasites, or who have distinctive clinical signs, and concomitantly high antibody titres. This paper investigates the performance of one serological method, the indirect fluorescent antibody test (IFAT), in detecting Leishmania infantum infection during an intensive 2-year cohort study of dogs in southern France. The results show that sensitivity and specificity with respect to infection can be simultaneously high, but maximum sensitivity is probably < 80%, and lasts for a relatively short period of 2-3 months after a lengthy incubation period. The IFAT gave the incidence of infection as 18-65% in the first year, whereas the best estimate of incidence based on parasite isolation and clinical observation was 72%. But data from the second year suggest that the 72% was itself an underestimate. We argue that, during epidemiological surveys, the IFAT in particular, and serological tests for leishmania in general, will underestimate prevalence, incidence and hence the scale of the control problem. However, there is evidence that tests for canine leishmaniasis employing high threshold titres will identify the most infectious animals, allowing selective treatment or culling of those which contribute disproportionately to transmission. PMID- 8519331 TI - The effects of stimulus novelty and familiarity on neuronal activity in the amygdala of monkeys performing recognition memory tasks. AB - The function of the amygdala in behavioural responses to novel stimuli and its possible function in recognition memory were investigated by recording the responses of 659 amygdaloid neurons in monkeys performing recognition memory and visual discrimination tasks. The aim was to determine the contribution of the amygdala in the encoding of familiarity and therefore its role in supporting memory-related neuronal mechanisms in the basal forebrain. The responses of three groups of neurons reflected different forms of memory. One group (n = 10) responded maximally to novel stimuli and significantly less so to the same stimuli when they were familiar. The calculated memory spans of these neurons were in the range of 2-10 intervening trials, and this short-term retention of information may reflect the operation of a neural mechanism encoding memory for the recency of stimulus presentation. Two other groups responded to the sight of particular categories of familiar stimuli: to foods (n = 6) or to faces (n = 10). The responses of some of these stimulus-selective neurons declined with repeated presentations of foods (3/4 tests) and faces (2/6 tests). The activity of these latter two groups of neurons may be involved in behavioural responses to familiar visual stimuli, particularly when such stimuli have affective or motivational significance. We conclude that the neurophysiological data provide evidence of amygdaloid mechanisms for the recognition of recently seen visual stimuli. However, these amygdaloid mechanisms do not appear to be sufficient to support the performance of long-term recognition memory tasks without additional and complementary functions carried out by other ventromedial temporal, prefrontal and diencephalic structures which also project to the basal forebrain. PMID- 8519332 TI - X and Y ganglion cells inform the cat's brain about contrast in the retinal image. AB - It has been suggested for a number of years that ganglion cells inform the rest of the brain about contrast in the retinal image. The purpose of the work undertaken here was to demonstrate this fact explicitly. Extracellular recordings were made from X- and Y-cell axons of the optic tracts of anesthetized cats. Responses of these cells to gratings that were near optimal in spatial and temporal frequency were measured for a range of contrasts. For each cell, similar measurements were made at a number of light levels, spanning the photopic to high scotopic (inclusive) ranges. A monotonic relationship between response and contrast was found at all light levels studied, and the same relationship was retained to a good approximation across all light levels. A similar result was also found when nonoptimal spatial frequencies were used as stimuli. These results indicate strongly that X and Y cells inform the cat's brain about contrast in the retinal image. It was also observed that the mean discharge rate of X and Y cells did not change with light level, indicating that no information is relayed to the brain by these cells on the mean light level. PMID- 8519333 TI - Effects of gaze on apparent visual responses of frontal cortex neurons. AB - Previous reports have argued that single neurons in the ventral premotor cortex of rhesus monkeys (PMv, the ventrolateral part of Brodmann's area 6) typically show spatial response fields that are independent of gaze angle. We reinvestigated this issue for PMv and also explored the adjacent prearcuate cortex (PAv, areas 12 and 45). Two rhesus monkeys were operantly conditioned to press a switch and maintain fixation on a small visual stimulus (0.2 degree x 0.2 degree) while a second visual stimulus (1 degree x 1 degree or 2 degrees x 2 degrees) appeared at one of several possible locations on a video screen. When the second stimulus dimmed, after an unpredictable period of 0.4-1.2 s, the monkey had to quickly release the switch to receive liquid reinforcement. By presenting stimuli at fixed screen locations and varying the location of the fixation point, we could determine whether single neurons encode stimulus location in "absolute space" or any other coordinate system independent of gaze. For the vast majority of neurons in both PMv (90%) and PAv (94%), the apparent response to a stimulus at a given screen location varied significantly and dramatically with gaze angle. Thus, we found little evidence for gaze-independent activity in either PMv or PAv neurons. The present result in frontal cortex resembles that in posterior parietal cortex, where both retinal image location and eye position affect responsiveness to visual stimuli. PMID- 8519334 TI - The control of slow orienting eye movements by tectoreticulospinal neurons in the cat: behavior, discharge patterns and underlying connections. AB - The activity of tectoreticulospinal neurons (TRSN) during orienting gaze shifts was studied in alert, head-fixed cats by intra-axonal recordings. The scope of the study was to evaluate the role of this class of superior colliculus neurons in the generation of slow eye movements (drifts) which often follow main-sequence saccades and sometimes appear as an independent motor event of orienting. The parameters of such movements are described in the first part of the paper. The organization of underlying pathways in the lower brainstem has been studied by intra-axonal horseradish peroxidase (HRP) tracing. The mean amplitude of postsaccadic drifts (PSD) is 1.21 degrees (SD 0.63), but it can eventually reach 6-8 degrees. PSDs have mean velocity of 14.9 degrees/s (SD 4.28) and mean duration of 104.2 ms (SD 50.8). These two parameters are positively correlated with PSD amplitude. The presence of PSDs is usually associated with an increased neck muscle activity on the side toward which the eyes move. The durations of these two motor events show a reliable positive correlation. PSDs appear to occur when gaze error persists after a saccade and a correction is attempted by means of a slow eye movement and a head turn. The durations of TRSN bursts are, on average, longer than the sum of the lead time and the saccade duration. Bursts associated with combinations of saccades and PSD are significantly longer than those recorded in the absence of PSDs. The probability of occurrence of PSDs is higher when firing of TRSNs continues after saccade termination. Such prolonged discharges usually coincide with a combination of PSDs and phasic activation of the neck electromyogram. The mean firing rate of TRSNs during PSDs is 62% of that during saccade-related portions of the burst and declines to 45% after the end of PSDs. According to its timing and intensity, postsaccadic firing of TRSNs is appropriate as a signal underlying slow, corrective eye movements and later portions of phasic neck muscle contractions during orienting. Intra-axonal HRP labeling showed that visuomotor TRSNs of the X type (n = 3) terminate in the abducens nucleus, with 145-331 boutons terminaux and en passant. Average bouton densities in the nucleus are lower than in the periabducens reticular formation, but higher than in more rostral paramedian pontine reticular formation (PPRF) regions. Terminal fields in the PPRF match the locations of "eye-neck' reticulospinal neurons (RSNs) and exitatory burst neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519335 TI - Memory for spatial locations, motor responses, and objects: triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex. AB - Based on behavioral procedures aimed at measuring working or data-based memory for spatial location, response, and visual object information, it is shown that there is a triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex in mediating spatial location, response, and visual object information, respectively. The hippocampus appears to subserve only spatial location, the caudate nucleus only response, and the extrastriate visual cortex only visual object information. The results support the neurobiological foundation of the attribute memory model. PMID- 8519336 TI - Synaptic mechanisms acting on lumbar motoneurons during postural augmentation induced by serotonin injection into the rostral pontine reticular formation in decerebrate cats. AB - Intrapontine microinjections of serotonin in acutely decerebrated cats resulted in the bilateral augmentation of the postural muscle tone of the hindlimbs. Optimal injection sites were located in the dorsomedial part of the rostral pontine reticular formation corresponding to the nucleus reticularis pontis oralis (NRPo). In this study, attempts were made to elucidate the cellular basis for the serotoninergically induced augmentation of postural muscle tone by recording the electromyographic (EMG) activity of hindlimb extensor muscles, the monosynaptic reflex responses evoked by electrical stimulation of group Ia muscle afferent fibres and the membrane potentials of hindlimb alpha-motoneurons (MNs). Serotonin injections resulted not only in the augmentation of the EMG activity of gastrocnemius soleus muscles, but also in the restoration of EMG suppression, which was induced by previous injection of carbachol into the NRPo. Extensor and flexor monosynaptic reflex responses were facilitated by serotonin injections into the NRPo. Such reflex facilitation was not induced by serotonin injections into the mesencephalic or the medullary reticular formation. Intrapontine serotonin injections resulted in membrane depolarization of extensor and flexor MNs with decreases in input resistance and rheobase. Spontaneous depolarizing synaptic potentials (EPSPs) increased in both frequency and amplitude. Peak voltage of Ia monosynaptic EPSPs also increased. Serotonin injections which followed carbachol injections resulted in membrane depolarization of MNs along with an increase in the frequency of spontaneous EPSPs and a decrease in carbachol-induced inhibitory postsynaptic potentials. Following pontine carbachol injections, antidromic and orthodromic responses in MNs were suppressed. Discharges of MNs evoked by intracellular current injections were also suppressed, but were restored following serotonin injections. These results indicate that postsynaptic excitation, presynaptic facilitation and disinhibition (withdrawal of postsynaptic inhibition) simultaneously act on the hindlimb MNs during serotonin-induced postural augmentation and restoration. PMID- 8519337 TI - Axons and axon terminals of cerebellar Purkinje cells and basket cells have higher levels of parvalbumin immunoreactivity than somata and dendrites: quantitative analysis by immunogold labeling. AB - The immunointensities of calcium-binding proteins parvalbumin (PV) and calbindin D28K were quantified in different parts of Purkinje cells and interneurons (basket cells and stellate cells) of the rat cerebellum. An electron microscopic, postembedding immunogold procedure on Lowicryl K4M-embedded thin sections was applied. Neuronal profiles were identified by double-labeling immunocytochemistry using the combination of the two primary antibodies, mouse monoclonal anti-rat calbindin D28K and rabbit polyclonal anti-rat PV. The secondary antibodies were conjugated with colloidal gold of different sizes (10 and 15 nm diameter). In the cerebellar cortex, double-labeled profiles were identified as Purkinje cells and profiles labeled only with anti-PV were identified as inteneurons. The densities of gold particles were used for statistical comparison of the relative levels of PV and calbindin D28K in somata, dendrites, dendritic spines, axons and axon terminals of Purkinje cells, and interneurons. The axons and axon terminals of Purkinje cells and basket cells had significantly higher levels of PV immunoreactivity than Purkinje cell somata, primary, secondary, and tertiary dendrites, and dendritic spines, as well as interneuron somata. On the other hand, the present study could not determine conclusively whether calbindin D28K was distributed homogeneously throughout soma, dendrites, and axons of Purkinje cells or was also concentrated in Purkinje cell axons. To estimate absolute PV concentrations, we made a series of artificial standard samples which were aldehyde-fixed 10% bovine serum albumin containing given concentrations of PV (0, 12.5, 25, 50, 100, 200, and 400 microM, 1 and 2 mM), and calibration curves were deduced from quantitative immunogold analyses of these standard samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519338 TI - Motor unit recruitment in human medial gastrocnemius muscle during combined knee flexion and plantarflexion isometric contractions. AB - Previous work on multifunctional muscle has suggested that motor unit recruitment during a combined force task is the result of an interactive effect of weighted inputs acting simultaneously on the motoneuron pool. The present study shows that a similar effect describes motor unit activation in a two-joint muscle as forces are combined at both proximal and distal attachments. The recruitment thresholds of single motor units in medial gastrocnemius muscle were determined during combined knee flexion and plantarflexion isometric contractions. Slow isometric ramp contractions in knee flexion were produced while maintaining various background levels of plantarflexion force. The combination of knee flexion and plantarflexion forces at which a motor unit initially discharged was used to characterize recruitment as represented by the slope of the regression line fit to the individual data points. Each subject completed two experiments; one at each of two knee joint angles, with the ankle joint fixed at 90 degrees. The effect of knee angle was assessed by comparing the slopes of the regression lines that characterized motor unit recruitment at each knee angle. Motor units in medial gastrocnemius were recruited when the linear sum of the forces exerted in plantarflexion and knee flexion exceeded a certain threshold of combined force. Specifically, the apparent force threshold of recruitment in knee flexion decreased as the level of force maintained in plantarflexion increased. Further, evidence is provided indicating that the linear relationship describing recruitment in two-joint muscle is dependent upon joint angle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519339 TI - Ontogenesis of head stabilization in space during locomotion in children: influence of visual cues. AB - The main purpose of this study was to investigate the development of the head stabilization in space strategy (HSSS) during various locomotor tasks in 3- to 8 year-old children and adults. The contribution of visual factors to the HSSS was also examined by applying peripheral visual restriction, stroboscopic visual motion cue restriction, and darkness. The kinematics of the head and trunk rotations (pitch, yaw, and roll) were analyzed by means of an optical TV-image processor (ELITE system). For each of the three angular components, an appropriate "head anchoring index" was defined in order to compare the HSSS with a head stabilization on the trunk strategy. Head-trunk correlation rates were also calculated for each angular component in order to evaluate the head-trunk stiffness. The development of head-trunk coordinations during locomotion under normal vision can be said to involve at least three main periods. The first period occurs from the age of 3 to 6 years, when the HSSS is adopted only while walking on the flat ground. While walking on narrow supports, children in this age-group rather tend to increase the head-trunk stiffness, especially at 6 years of age. The second period includes 7- to 8-year-old children. Children of this age become able to adopt the HSSS while walking on narrow supports. During this period, the HSSS is associated with a large decrease in the head-trunk correlations. Lastly, in adulthood the HSSS is commonly adopted but specifically involves the roll component associated with the lateral body oscillations while walking. Vision was found to have little influence on children's HSSS while walking, whatever their age. Moreover, darkness induces an increase in the efficiency of the HSSS in adults. This confirms that the HSSS is the most appropriate strategy available for dealing with an increase in the level of equilibrium difficulty and may reflect a "top-down" organization of the postural control while walking. These results also suggest that the HSSS may be mainly of vestibular origin and presumably serves to facilitate the visual input processing, particularly that of the motion and peripheral visual cues which are involved in the control of body equilibrium during locomotion. PMID- 8519340 TI - Monocular and binocular neuronal activity in human visual cortex revealed by electrical brain activity mapping. AB - In the present study, we investigated topographical differences between monocularly and binocularly evoked potential fields related to the retinal location and spatial frequency of grating stimuli. Electrical brain activity was recorded in 18 healthy adults using an array of 21 electrodes over the occipital areas. Vertical black-and-white grating patterns of different spatial frequencies were presented with central fixation or lateralized to the left or right hemiretina. Computation of global field power determined component latency. Topographic characteristics of the field distributions were examined at the individual component latency for each subject using statistical comparisons between experimental conditions. The strength of the potential fields was significantly larger with binocular stimuli, whereas no effects were observed when comparing component latencies. Pronounced differences occurred in the spatial distribution of electrical brain activity: with 2.5 cycles/deg, large, significant topographic differences between monocularly and binocularly evoked activity were obtained. The potential fields showed a more anterior and more lateralized component distribution with binocular than monocular stimuli. In addition, when the gratings were presented binocularly, significant topographic differences were observed when low and high spatial frequency stimuli were compared. Our results suggest that the relationship between the topography of evoked components and retinal stimulus location and spatial frequency is different for monocular and binocular stimuli, indicating that binocular information processing triggers different neuronal processes in the human visual cortex. PMID- 8519341 TI - Three-dimensional analysis of strongly curved saccades elicited by double-step stimuli. AB - Earlier recordings of eye position in three dimensions have revealed that Listing's law is obeyed in reasonable approximation, both statically and dynamically. This implies that all eye positions are confined to a plane when using a rotation vector or quaternion representation. The orientation of the angular velocity axis is crucial in order to preserve the law. For a single-axis rotation, the eye's angular velocity axis has to tilt out of Listing's plane, otherwise the law cannot be preserved in eccentric saccades. Experimental work has confirmed that normal, visually-guided saccades resemble single-axis rotations whose angular velocity axis tilts by the right amount. We investigated how well the saccadic system implements Listing's law when the trajectory of the eyes is more complicated, as in a non-single-axis rotation where the angular velocity vector depends on instantaneous eye position. Eye position was measured in three dimensions using the magnetic scleral search coil method for five subjects. Non-single-axis rotations of the eye were evoked with a double-step paradigm. We found that Listing's law is obeyed equally well during fixations, single-axis saccades and in non-single-axis saccades. Some deviations from the law were found in both curved and single-axis eye movements, but we demonstrated that the net torsional component of eye position of these saccades is negligible compared to that expected if the angular velocity axis did not tilt at all. In addition, analysis of the angular velocity signals in the curved movements showed strong similarity to the computed signal required for implementing Listing's law. Our results show that the observed deviations from Listing's law reflect only minor failures in the mechanism underlying its dynamic implementation. We conclude that single-axis rotations are not a necessary condition for the implementation of Listing's law in saccades. Our results are compatible with the notion that the implementation of Listing's law relies upon internal feedback. Various suggestions of how models can be reconciled with recent data on the three dimensional control of saccades are discussed. PMID- 8519343 TI - Atherosclerosis alters the localization of HSP70 in human and macaque aortas. AB - Evidence suggests an important role for heat shock proteins (HSPs) in the evolution of atherosclerotic necrotic cores. The present study compared normal appearing and atherosclerotic aortas obtained from control and diet-induced atherosclerotic cynomolgus macaques and from human autopsies, with respect to the localization and content of 70-kDa HSPs (HSP70). The distribution pattern of HSP70 was determined by immunostaining tissue sections with anti-HSP70 monoclonal antibody against both constitutive and inducible isoforms. Changes in HSP70 staining with developing atherosclerosis were quantitated using video morphometry. Total aortic HSP70 content was evaluated by Western blotting tissue homogenates. In both macaque and human aortas, HSP70 staining was homogeneous in normal-appearing regions, but developed a heterogeneous pattern in the presence of atherosclerosis. Immunostaining for three other HSPs (90, 65, and 28 kDa) confirmed the change as HSP-specific. Video morphometry indicated a significant positive association between severity of atherosclerosis and altered patterns of HSP70 staining. However, Western blots detected no difference in total HSP70 content of either human or macaque aortas with plaque progression. The data suggest HSP70 localization changes in aortas during atherosclerosis evolution without affecting overall aortic HSP70 content. Such changes in HSP70 localization may reflect differences in the cellular response and resistance to cytotoxic conditions present within the plaque, which could influence the expansion of necrotic cores. PMID- 8519342 TI - Transformations between visual and kinesthetic coordinate systems in reaches to remembered object locations and orientations. AB - The abilities of human subjects to perform reach and grasp movements to remembered locations/orientations of a cylindrical object were studied under four conditions: (1) visual presentation of the object-reach with vision allowed; (2) visual presentation-reach while blindfolded; (3) kinesthetic presentation of the object-reach while blindfolded and (4) kinesthetic presentation-reach with vision. The results showed that subjects were very accurate in locating the object in the purely kinesthetic condition and that directional errors were low in all four conditions; but, predictable errors in reach distance occurred in conditions 1,2, and 4. The pattern of these distance errors was similar to that identified in previous research using a pointing task to a small target (i.e., overshoots of close targets, undershoots of far targets). The observation that the pattern of distance errors in condition 4 was similar to that of conditions 1 and 2 suggests that subjects transform kinesthetically defined hand locations into a visual coordinate system when vision is available during upper limb motion to a remembered kinesthetic target. The differences in orientation of the upper limb between target and reach positions in condition 3 were similar in magnitude to the errors associated with kinesthetic perceptions of arm and hand orientations in three-dimensional space reported in previous studies. However, fingertip location was specified with greater accuracy than the orientation of upper limb segments. This was apparently accomplished by compensation of variations in shoulder (arm) angles with oppositely directed variations in elbow joint angles. Subjects were also able to transform visually perceived object orientation into an appropriate hand orientation for grasp, as indicated by the relation between hand roll angle and object orientation (elevation angle). The implications of these results for control of upper limb motion to external targets are discussed. PMID- 8519344 TI - Glycan structure of blood group-A antigen in hamster normal tissues and pancreatic cancers. AB - Pancreatic cancers induced by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters produce blood group A antigen. The glycan structure of the blood group A antigen bearing glycoproteins purified from pancreatic cancer cells has been shown previously to be bound to Asn-linked complex oligosaccharides. Because blood group A antigen has usually been described as being on Ser/Thr-linked glycans, the distribution and glycan-protein linkage of the antigen were examined in normal hamster tissues in comparison with the findings on pancreatic cancer cells. The gastrointestinal tract, excluding the small intestine, expressed blood group A antigen. The liver, pancreas, and gallbladder did not show blood group A reactivity. Blood group A antigen in the proximal gastrointestinal tract was resistant to peptide N-glycosidase F digestion, which cleaves Asn-linked glycans from core proteins. Blood group A antigen was peptide N-glycosidase F sensitive in membrane preparations from pancreatic cancers. In the colon, this antigen was only partially removed by peptide-N-glycosidase F. These results demonstrate a difference in the structure of blood group A antigen-associated glycan between pancreatic cancers and normal hamster gastrointestinal tissues. PMID- 8519345 TI - The influence of phthalate esters on Leydig cell structure and function in vitro and in vivo. AB - Phthalate esters are widely used in the manufacture of plastics and have been shown to cause testicular toxicity, purportedly, by targeting the Sertoli cell alone. Recent evidence, however, indicates that a paracrine control exists between Sertoli and Leydig cells and the breakdown of one component of this relationship is therefore detrimental to normal function. However, no data that explore the influence of testicular toxins on Leydig cell structure and function have been published hitherto. The preliminary studies reported here were initiated to test the hypothesis that phthalate intoxication may adversely alter Leydig cell structural and functional integrity. Four phthalate esters, namely, di(2-ethylhexyl) phthalate (DEHP, di-n-pentyl phthalate (DPP)., di-n-octyl phthalate (DOP), and diethyl phthalate (DEP) were investigated in vivo and their monoesters (MEHP, MPP, MOP, and MEP, respectively) in vitro for indications of Leydig cell toxicity in the rat. Rats were dosed by oral gavage with 2 g phthalate diester/kg/day in corn oil vehicle for 2 days, while Leydig cell primary cultures were incubated with 1,000 microM monoester for 2 hr. Light and electron microscopy were undertaken to determine the type and degree of any changes. Phthalate esters exerted a direct effect on Leydig cell structure and function (as determined by testosterone output) with correlation of the in vitro and in vivo effects of MEHP (DEHP) and MOP (DOP). No effects on Leydig cell structure or function were seen with MPP (DPP), although Sertoli cell cytoplasmic rarefaction and vacuolation were observed in vivo. DEP produced Leydig cell ultrastructural alterations in vivo. We conclude that individual phthalate esters may exert effects on both Sertoli and Leydig cells or one cell type alone. PMID- 8519346 TI - Prevention of CCl4-induced liver necrosis by the calcium chelator arsenazo III. AB - Arsenazo III (AIII) (100 mg/kg ip in saline) administration to Sprague-Dawley male rats 30 min before or 6 or 10 hr after CCl4 [1 ml/kg ip as a 20% (v/v) solution in olive oil] significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as demonstrated either by histology or by determination of isocitric acid dehydrogenase in plasma. AIII did not modify the CCl4 concentrations reaching the liver, the intensity of the covalent binding of CCl4-reactive metabolites to hepatic microsomal lipids, or the CCl4-promoted lipid peroxidation process at either 1 or 3 hr of poisoning. AIII administration enhanced glutathione (GSH) levels in liver and significantly prevented the CCl4 induced minor decreases in GSH content and the CCl4-induced increases in calcium content at 24 hr of intoxication. AIII treatment further enhanced the CCl4 induced decreases in body temperature of the poisoned rats. Results suggest that AIII's preventive effects might be related to its very well-known calcium chelating properties, but that additional factors related to AIII's ability to increase GSH content in liver or to decrease body temperature of CCl4-intoxicated animals may also play a role. PMID- 8519347 TI - Mercury in the rat hypothalamic arcuate nucleus and median eminence after mercury vapor exposure. AB - A histochemical technique has been used to reveal mercury deposits in the hypothalamic arcuate nucleus and median eminence of adult male rats. After exposure to long-term, low-level or short-term, high-level mercury vapor, silver enhanced mercury grains were found in neurons of the arcuate nucleus. In addition mercury deposits were found in tanycytes, ciliated ependymal cells, and in the walls of capillaries. The mechanisms underlying uptake and possible induction of toxic effects are discussed. PMID- 8519348 TI - Detection of mercury in rat spinal cord and dorsal root ganglia after exposure to mercury vapor. AB - Adult male Wistar rats were exposed to mercury vapor, 50 micrograms Hg/m3, 6 hr/day, 5 days/week, over 1-, 2-, 3-, 4-, 6-, and 8-week periods. Sections from the spinal cord and dorsal root ganglia from spinal levels C1, C5, T6, and L1 were stained with the autometallographical technique and the distribution of mercury deposits described at light and electron microscopical levels. A quantitative analysis of the amount of mercury in blocks of the spinal cord was performed using cold vapor atomic absorption spectrophotometry. After an exposure period of 2 weeks, silver-enhanced mercury grains could be observed in spinal cord neurons located in Rexed laminae IV-X. Ventral horn motoneurons were heavily stained in all of the spinal cord segments. Ependymal cells and glial cells of both the spinal gray and white matter contained cytoplasmatic mercury accumulations in rats exposed to mercury vapor for 4 weeks. In the dorsal root ganglia, only ganglion cells showed a faint mercury staining and the amount of staining was notably less than that seen in the ventral horn motoneurons. At the ultrastructural level, mercury was seen primarily within lysosomes of target cells. The quantitative mercury measurements demonstrated that spinal cords from rats exposed to mercury vapor for 6 or 8 weeks contained a significantly higher concentration of mercury than those from control animals. PMID- 8519349 TI - An interview study to estimate prevalence of asthma and chronic bronchitis. The obstructive lung disease in northern Sweden study. AB - A questionnaire of respiratory symptoms and diseases completed by 6610 adults in 3 age cohorts (35-36 y; 50-51 y and 65-66 y) in northern Sweden was followed-up by interview and lung function testing of 1243 subjects with asthmatic or bronchitic symptoms and 263 subjects assessed from the postal questionnaire as being healthy. We report the results of this follow-up study. According to the criteria used, 292 subjects (5.1% of the original study sample) were diagnosed as having asthma. Out of the 1243 subjects 334 (5.9% of the original study population) were diagnosed as having chronic bronchitis. However, examination of the 263 subjects who were healthy according to the postal questionnaire showed that elderly smokers, in particular, under-reported bronchitic symptoms; taking this into account, the prevalence of chronic bronchitis is estimated to be of the order of 9%. Diagnostic difficulties were noted in 70 subjects (corresponding to 1.2% of the original study sample) in whom asthma or chronic bronchitis were strongly suspected. Further investigation of these subjects was considered necessary. In this cross-sectional study, FEV1 < 80% of predicted values was found in 36% of subjects diagnosed as having asthma and in 31% of those with chronic bronchitis. Among subjects with attacks of breathlessness and wheezing, diagnostic criteria often used for asthma in questionnaire studies, 70% were diagnosed as having asthma. Of those with chronic productive cough, 62% were diagnosed as having chronic bronchitis. We consider that trained nurses provide reliable data that may be used in epidemiological surveys of obstructive lung diseases. PMID- 8519350 TI - High blood pressure and the incidence of non-insulin dependent diabetes mellitus: findings in a 11.5 year follow-up study in The Netherlands. AB - To examine the contribution of cardiovascular risk factors to the development of non-insulin dependent diabetes mellitus, a prospective follow-up study was performed of a cohort, initially examined in a population survey on cardiovascular risk factors. The survey was conducted from 1975 to 1978 in the Netherlands among 5700 men and women aged 20 to 65. In 1988 a questionnaire on the prevalence of chronic diseases, including diabetes mellitus, was sent to all living participants of the initial survey. The general practitioners of the persons who indicated to have diabetes mellitus were asked to confirm the diagnosis. Diabetes mellitus was defined as current use of oral hypoglycemic drugs or insulin. After exclusion of the prevalent cases at the initial survey, 65 incident confirmed cases remained. All others responding to the questionnaire served as controls. The incidence of diabetes mellitus was associated with body mass index, use of diuretics, systolic and diastolic blood pressure. After adjustment for age and body mass index systolic and diastolic blood pressure were still associated with the incidence of non-insulin dependent diabetes mellitus in men; relative risks 1.28 (95% confidence interval 1.06-1.54) and 1.40 (95% CI 1.06-1.85) per 10 mmHg respectively. For women, only the relative risk associated with the use of diuretics remained statistically significant (2.26, 95% CI 1.04 4.90). This probably reflects the risk of (treated) hypertension: adjusted for blood pressure, the relative risk lost statistical significance. These findings suggest that elevated blood pressure is a risk for the development of non-insulin dependent diabetes mellitus (NIDDM). This supports the view that NIDDM and hypertension may have a similar origin. PMID- 8519351 TI - The relationship between coffee consumption and serum cholesterol under consideration of smoking history. AB - A large German population sample of 6820 men and 7258 women was used to investigate the relationship between coffee consumption, total serum cholesterol and HDL cholesterol. Analyses were conducted on men and women separately. Differences in age, body mass index, diastolic blood pressure, smoking habits, alcohol, fish, milk and tea consumption, physical activity and medication use were controlled for in the analyses. Interactions between coffee consumption and smoking habits in their relationship with serum cholesterol were part of the analyses. For men, a positive relationship between coffee consumption and total serum cholesterol was found among smokers and life-long abstainers but not in the group of ex-smokers. In women a relationship between coffee consumption and total serum cholesterol was also present, but very weak (only statistical significant in covariance analyses). Levels of HDL cholesterol did not correlate with coffee consumption in either men and women. Hypotheses concerning the peculiarities of the group of ex-smokers are developed, and supporting empirical evidence is given. It is suggested that the group of ex-smokers should always be analysed separately. PMID- 8519352 TI - Stroke care in the next decades: a projection derived from a community-based study in Umbria, Italy. AB - Recently published data show that stroke incidence is not longer declining, while case fatality rates has had a less pronounced fall in recent years than in the past. Projections of the increasing number of elderly people, combined with the greater risk of stroke in old age, suggest that in the forthcoming decades we will be faced with an increased request of health resources for patients with stroke. We have therefore used data from a community-based study on stroke incidence and outcome to project the number of first ever strokes, death from stroke and handicap from stroke in Italy, up to the year 2016. Results show that incidence will increase by 22.2%, and death at 6 months from first ever stroke by 29%. However, since patients already handicapped for other reasons are more likely to die from their stroke, the net number of newly handicapped persons will only increased by 5%. These results suggest that in the next decades the major increase in request of health care resources will result from the acute event and the immediate post-ictal phase, and not from the management of chronic handicap after a stroke. PMID- 8519354 TI - Counselling and testing for HIV infection in Rome 1985-1990: analysis of client characteristics and seroprevalence. AB - To analyze the characteristics of persons seeking HIV testing, and to evaluate the potential effectiveness of a regional program of confidential counselling and testing for HIV infection, we reviewed data on 5127 clients seen from July 1985 to December 1990 in a major counselling and testing site of the city of Rome. During the study period, the number of clients attending the service increased without a parallel rise of the number of newly identified HIV seropositive subjects. Consequently, the seroprevalence rate decreased from 27.6% in the second half of 1985, to 4.3% in the second half of 1990 (p < 0.001). This decrease appears to be associated with the increasing attendance of low risk subjects and of those referred for testing by family practitioner. The study suggests the need for more efficient strategies to reach persons at higher risk for HIV infection. PMID- 8519353 TI - Reference values for serum zinc and selenium of French healthy children. AB - Age - and sex-specific reference intervals derived from a healthy pediatric population are presented for zinc, selenium and related analytes in serum. No strong correlations were found between age, sex and trace elements in serum. Serum variables were discussed to assess their ability as biochemical indicators of micronutrient status in the field of biological epidemiology. PMID- 8519355 TI - Demand patterns for HIV-tests in general practice: information collected by sentinel networks in 5 European countries. AB - This study describes a 1 year international data collection on the demand pattern for HIV-antibody tests in general practice recorded by 6 sentinel networks in 5 European countries. The purpose of the recording was to evaluate the use of HIV antibody testing by general practitioners and the demand for testing among the general population. Sentinel networks of general practitioners are a possible and available instrument for monitoring the perception of the HIV-test, and indirectly of the threat of the HIV-epidemic by the public and by the general practitioners (GPs). Differences were found between the countries in the frequency of testing, the person asking the test and the reason for testing. Possible explanatory factors, such as differences in the routine testing of specific groups, differences in the training and in the role of the GP, differences in the characteristics of prevention policy, are discussed. The European comparison also offers the opportunity to reflect on common medical practice in dealing with demands for HIV-tests. PMID- 8519356 TI - AIDS and tuberculosis. AB - Between 1985-1989 were diagnosed 376 cases of TBC in "La Fe" hospital in Valencia. 36 of this cases also had AIDS. We have carried out a compared study among the 340 cases of TBC and the 36 cases of AIDS+TBC. In this way we have described the social and work conditions of both groups, the hospitalization, the associated pathologies, the different risk factors, the different characteristics of the disease in each group of TBC, the diagnoses methods and the treatment of each case. PMID- 8519357 TI - Serotype patterns of gonococcal infection in contact pairs. AB - The use of gonococcal serovars in studying the epidemiology of Neisseria gonorrhoeae is well established. Most studies assume that the isolated serovar remains stable in vivo indefinitely. This study was designed to observe the correlation between serovars isolated in patients naming each other as sexual contacts. The overall rate of discordant transmission episodes was 12% (26/220). There were however significantly more discordant transmission episodes for partners of patients infected with IB serovars than IA serovars: 19% (23/124) versus 3% (3/96) - p < 0.01. The overall prevalence of serogroup IB isolates although significantly higher at 53% (p < 0.01) was thought insufficient to account for the correlation between discordant pairs and serogroup IB infection. Reasons considered for the discrepancies in contact pairs included: problems of partner reporting involving inaccurate or incomplete information; technical problems with reagents; culture induced phenotypic variation in antigenic expression or differences in the in vitro recognition of epitopes; and antigenic differences resulting from genetic mutation within the Protein I gene. It was concluded that carefully planned and controlled prospective studies involving duplicate parallel testing of isolates from patients and their well documented partners are needed to assess the extent to which these various factors contribute to discordancies in serovars isolated from contact pairs. Serotyping should be combined with other methods such as auxotyping for detailed microepidemiological studies involving partner notification. PMID- 8519358 TI - Immune response to simultaneous administration of a combined measles, mumps and rubella vaccine with booster doses of diphtheria-tetanus and poliovirus vaccine. AB - A combined vaccine against measles (Edmonston-Zagreb 19 strain), mumps (Rubini strain) and rubella (Wistar RA 27/3 strain) was administered to a group of 46 children aged 10-12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoid and oral poliovirus vaccine. A second group of 53 children aged 15-24 months who had received booster doses of the compulsory vaccines 5 to 12 months before was also vaccinated. The same seroconversion rates (100%) and similar antibody titers for rubella were observed in both groups. The same seroconversion rates for mumps (93%) and similar rates for measles (98 and 94%) were observed in the two groups. Significantly lower antibody titers for measles and mumps were found in the first group, but they were compensated by an earlier protection, a reduction of number of visits for immunization, costs for the community, and improvement in parental compliance. These results confirm that Edmonston-Zagreb 19 and Rubini strains are still immunogenic even when they are combined with Wistar RA 27/3 strain. Moreover, a long term follow-up in order to verify the persistence of protective antibody levels in both groups of children, could suggest that combined measles, mumps and rubella vaccine could be given earlier (at 10-12 months of age), simultaneously with booster doses of diphtheria and tetanus toxoid and of trivalent oral poliovirus vaccine. PMID- 8519359 TI - Transmission of antibodies to Chlamydia psittaci and Coxiella burnetii through eggs and "crop milk" in pigeons. AB - Young semi-domesticated pigeons captured or hatched from eggs gathered in Bratislava during 1989-1991 were examined for complement fixing antibodies to Chlamydia psittaci and agglutinating antibodies to Coxiella burnetii. Antibodies to Ch. psittaci were present in 76% of birds younger than 24 h, in 47.7% between 1 and 10 days of age and in 12% of nestlings over 10 days old. Antibodies to Ch. psittaci were also detected in "crop milk" of 4.1% of 1 to 10 day old birds and in 4.5% of specimens older than 10 days. Antibodies to C. burnetii were not found in juvenile birds under 24 h old, but antibodies against this agent were present in 16.4% birds between 1 and 10 days old and in 18% over 10 days old. Antibodies to C. burnetii were also detected in "crop milk" collected from crops of 2% of the young birds between 1 and 10 days. PMID- 8519360 TI - A survey of Q-fever in Sweden. AB - Coxiella burnetii, the etiological agent of Q-fever has recently been isolated from sheep in southern Sweden. In this region 24-30% of sheep farmers have been exposed to the organism as shown by serological measurements. In veterinarians, another group with high risk of exposure to C. burnetii, about 12% have antibodies to the bacteria. The seropositive veterinarians are scattered all over the country. In two non-risk groups, draftees and hospital employees, 5-7% were found to be positive. This survey showed that Q-fever is a domestic disease which is spread throughout Sweden. PMID- 8519362 TI - Prevalence of Yersinia antibodies in blood donors. AB - Agglutinins titers against Y. enterocolitica 0:3, 0:5, 0:9 and Y. pseudotuberculosis I were determined by the microagglutination method in 777 blood donor sera. Titers of < or = 1/10 were observed in 93.5% of the subjects for Y. enterocolitica 0:3, in 87.8% for Y. enterocolitica 0:9 and in 95.1% for Y. enterocolitica 0:5 and for Y. pseudotuberculosis I. Low level titers (1/10 - 1/20) were found in 11.4% to 23.1%. Titers of > or = 1/40 were observed in 1.7% for Y. enterocolitica 0:3, in 1.4% for Y. enterocolitica 0:5, in 5.1% for Y. enterocolitica 0:9 and in 1.2% for Y. pseudotuberculosis I. Titers of > or = 1/80 were seen in 0.2% for Y. enterocolitica 0:3, in 0.1% for Y. enterocolitica 0:5 and in 1.3% for Y. enterocolitica 0:9. Only in one donor's serum was a titer of 1/160 against Y. enterocolitica 0:9 found. The upper limit of normal titer at 15% cutoff level against Yersinia antigens, found in blood donor sera by the microagglutination test, was 1/10. PMID- 8519361 TI - Etiology of traveller's diarrhea in Spanish travellers to developing countries. AB - A cohort of 337 Spanish travellers to developing countries is presented. They all consulted us for traveller's diarrhea (TD). Bacteriological, parasitological and virological examinations were performed. A bacterial cause was found in 61.65% of travellers. Toxigenic and classical pathogenic Escherichia coli strains were the main bacterial agents. In comparison with other studies, Spanish travellers harboured Y. enterocolitica and EPEC organisms as a cause of TD. G. lamblia and E. histolytica were the most frequently isolated protozoa. Helminths were found in only 9 patients. No rotavirus infections were diagnosed. Previous antibiotic treatment had been taken by 161 patients. The percentage of isolated enteropathogens was similar in travellers who had previously taken antibiotic treatment and those who had not. PMID- 8519363 TI - The periodontal treatment needs of Malagan adults. AB - The Periodontal treatment needs of 908 subjects aged 18-64 years in Malaga, Spain were assessed using the Community Periodontal Index of Treatment Needs (CPITN). The percentage of subjects scored periodontally healthy decreased with age, 18-64 yrs., from 22% to 3%. Conversely periodontal pocketing increased with age from 2% to 55%. Calculus was a very prevalent score at all ages, about 60% overall. No significant differences in periodontal treatment needs were identified among the three defined socio-economic groups, but the health professional group had fewer periodontal pockets than the other two groups. Treatment needs increased significantly with age in all groups. For the WHO standard age group 35-44 yrs 8% of 180 were scored healthy, 66% were scored for calculus or bleeding only, 23% with shallow pockets and 3% with deep pockets. An average of 2 out of 6 sextants were found health and 2.6 (43%) had calculus or other retentive factors. PMID- 8519364 TI - Toxoplasma gondii pneumonia in Italian patients infected with HIV. PMID- 8519365 TI - HIV seroprevalence at the Obstetrics Hospital in Turin, Italy. PMID- 8519366 TI - The CO2 response: usefulness and uncertainties. PMID- 8519367 TI - Exercise-induced asthma in children. PMID- 8519368 TI - Measuring bronchial responsiveness in epidemiology. PMID- 8519369 TI - Respiratory response to CO2 in patients with chronic obstructive pulmonary disease in acute respiratory failure. AB - The aim of our study was to determine the importance of chemoreceptor stimulation by carbon dioxide in setting the level of ventilation in patients with chronic obstructive pulmonary disease (COPD) in acute respiratory failure. We studied the ventilatory and mouth occlusion pressure (P0.1) responses to CO2 in 25 COPD patients under treatment for episodes of acute respiratory failure, and in 24 normal subjects. Carbon dioxide rebreathing tests were performed in the spontaneously breathing, intubated patients, after arterial blood gases had been quasi-normalized by mechanical ventilation, which allowed us to compare both groups at similar resting arterial carbon dioxide tension (PaCO2) and acid-base status. The slopes of the ventilatory responses were markedly lower in the patients (mean +/- SEM, 1.28 +/- 0.23 versus 12.53 +/- 1.13 l.min-1.kPa-1). The slopes of the P0.1 responses were lower in the patients (0.27 +/- 0.05 versus 0.45 +/- 0.05 kPa.kPa-1), but the absolute P0.1 values were not significantly different from the normals. Increasing PaCO2 from 5.3 to 8 kPa (40 to 60 mmHg) resulted in a mean increase of 34% in ventilation. These results show that CO2 drive is a major determinant of respiratory stimulation in many COPD patients with acute respiratory failure. PMID- 8519370 TI - Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood gases and control of breathing in severe COPD. AB - Patients with severe chronic obstructive pulmonary disease (COPD) commonly complain of insomnia, but hypnotic drugs are generally not recommended due to their depressant effect on the respiratory centres. The aim of this study was, therefore, to compare the effects of a single dose of the benzodiazepine hypnotics, triazolam 0.25 mg and flunitrazepam 1 mg, and a new imidazopyridine compound, zolpidem 10 mg, in hypercapnic COPD patients. Twelve stable COPD patients (mean +/- SD arterial oxygen tension (PaO2) 9.3 +/- 0.8 kPa and arterial carbon dioxide tension (PaCO2) 5.9 +/- 1.9 kPa) were included in the study. The following measurements were performed before and 2 h after drug administration: PaO2 and PaCO2, minute ventilation (VE), mouth occlusion pressure (P0.1), rebreathing CO2 tests with ventilatory response to carbon dioxide stimulation (delta VE/delta PACO2) and mouth occlusion pressure response to carbon dioxide stimulation (delta P0.1/delta PACO2). The measurements were performed in a randomized, double-blind fashion, each patient receiving a single dose of each drug on three different days, separated by a one week interval. No difference was noted between control measurements and those taken 2 h after administration of zolpidem in the following parameters: PaCO2, PaCO2, VE, P0.1, delta VE/delta PACO2 and delta P0.1/PACO2. Two hours after administration of triazolam and flunitrazepam, a significant difference was noted in VE for triazolam and for flunitrazepam. After flunitrazepam administration, a significant decrease in PaCO2 (6 +/- 1.8 at baseline versus 7 +/- 0.4 kPa), and delta VE/PACO2 (0.44 +/- 0.20 at baseline versus 0.31 +/- 0.21 l.min-1 x kPa) were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519371 TI - The effects of five years of nocturnal cuirass-assisted ventilation in chest wall disease. AB - We investigated the long-term effectiveness of cuirass-assisted ventilation, and examined whether mortality and morbidity could have been predicted at the time of admittance. Twenty five patients were commenced on nocturnal cuirass-assisted ventilation between 1983 and 1985, 10 with scoliosis or kyphosis, 8 with a thoracoplasty and 7 with neuromuscular disease. Mean pretreatment vital capacity was 30% of predicted, and arterial carbon dioxide tension (Paco2) was 8.2 kPa (62 mmHg). Fifteen patients were alive 5 yrs later. Two had discontinued assisted ventilation, both dying soon afterwards, and three had been changed to intermittent positive pressure ventilation. Survival could not have been predicted from age, severity of disease, lung volumes or arterial blood gases at presentation. Paco2 in the survivors had risen from a mean of 6.1 kPa (46 mmHg) after one year to 6.8 kPa (52 mmHg) after 5 yrs (p < 0.05), but remained significantly less than at presentation. There were no significant change in arterial oxygen tension (Pao2), lung volumes, respiratory muscle strength, haemoglobin, right heart failure, exercise tolerance, mental function and symptom scores after 5 yrs, compared to after 1 yr. The median amount of time spent in hospital declined from 15 days per patient in the first year after initial discharge with cuirass-assisted ventilation, to between 3-5.5 days per patient in subsequent years. We conclude that nocturnal cuirass-assisted ventilation has a role in long-term management of patients with neuromuscular and skeletal chest wall disorders. A randomized comparison with nasal intermittent positive pressure ventilation is now indicated. PMID- 8519372 TI - How do patients with either asthma or COPD perceive acute bronchodilation? AB - The purpose of this study was to assess the perception of bronchodilation, as a change in shortness of breath on a bipolar visual analogue scale (VAS), in 16 asthmatics and 20 subjects with COPD. Bronchodilation was gradually induced by five consecutive terbutaline inhalations (cumulated dose 800 micrograms). The subjects were categorized into high and low perceivers, on the basis of a cut-off of 25% VAS line length (after the fifth inhalation). The quality of perception was studied on a within-subject basis by linear regression analysis of VAS ratings against changes in lung function, and was characterized in terms of strength of correlation (squared correlation coefficient, r2), slope, and VAS axis intercept. Fourteen out of 16 asthmatics, and 13 out of 20 COPD subjects, were high perceivers. In the COPD group, the high perceivers had a larger objective response--particularly in inspiratory vital capacity--than the low perceivers. The strongest correlation between subjective and objective response was obtained in asthmatics when the improvement in shortness of breath was evaluated against the decrease in specific inspiratory resistance (median r2 = 0.831). In COPD low perceivers, subjective and objective response were unrelated, while COPD high perceivers differed from the asthmatics by larger intercepts. The perceptual characteristics were unrelated to the degree of baseline obstruction, whilst a modest relationship (r = 0.51) was found between the increase in forced expiratory volume in one second (FEV1) and r2 of the VAS/delta FEV1 analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519373 TI - Assessment of bronchodilator response in children with asthma. Dutch CNSLD Study Group. AB - The bronchodilator response (BDR) in forced expiratory volume in one second (FEV1) is routinely assessed to estimate the reversibility of airways obstruction. However, there is no consensus on how the BDR should be expressed, and recommendations applying to children are lacking. Similarly, the relationship between BDR and nonspecific bronchial hyperresponsiveness to histamine (BHR) has not been elucidated. These questions were addressed in 116 children, 7-16 yrs of age, with stable asthma after withdrawal of all pulmonary maintenance medication. Inclusion criteria were an initial FEV1 between 55-90% predicted, and/or FEV1/forced vital capacity (FVC) between 50-75%, as well as a fall in FEV1 of 20% or more when challenged with up to 150 micrograms histamine. The change in FEV1 (delta FEV1) 20 min after inhalation of 800 micrograms salbutamol was expressed in four ways: as an absolute difference (delta FEV1(l)), as a percentage of predicted FEV1 (delta FEV1%pred) or initial FEV1 (delta FEV1%init), and as a percentage of the deficit in FEV1 (delta FEV1%(pred-init)). delta FEV1%init and delta FEV1%pred were not related to age and stature of the children; delta FEV1%(pred-init) was related to stature, whilst delta FEV1(l) was related to both age and stature. All indices correlated with initial FEV1. However, this is an artefact introduced by relating change to initial value, rather than to the mean of initial and final value. In fact, BDR, expressed as delta FEV1%pred, was only slightly greater in children with the lowest initial airway calibre (p = 0.08), unlike delta FEV1%init. BDR was weakly related to BHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519374 TI - The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group. AB - The effect of long-term treatment with inhaled corticosteroid on exercise-induced asthma (EIA) was studied in 55 children, aged 7-18 yrs (mean 12 yrs). We also compared the time course of stabilization of EIA to that of other indicators of airway responsiveness, such as peak expiratory flow (PEF) variation and the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1). All children participated in an ongoing multicentre study to compare the effects of long-term treatment either with the beta 2-agonist salbutamol (600 micrograms.day-1) plus the inhaled corticosteroid budesonide (600 micrograms.day-1) (BA+CS), or salbutamol plus placebo (BA+PL), on airway calibre, airway responsiveness and symptoms. After a median follow-up of 22 months, the study design had to be changed, because of the high number of drop-outs on BA+PL. At that time, the treatment regimen of all children who had not withdrawn was changed into BA+CS. At the moment of change, and after 2 and 8 months of treatment, a treadmill exercise test was performed in two centres. Eighteen of the 22 children (82%) who were treated with BA+PL from the beginning had EIA, compared to 18 of the 33 children (55%) who were treated with BA-CS (p < 0.05). After 2 and 8 months of treatment with BA+CS in the patients previously on BA+PL this percentage decreased to 59 and 55%, respectively, and was not significantly different between both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519375 TI - The state of childhood asthma in young adulthood. AB - We investigated whether patients with childhood asthma had improved when reaching adulthood. We also evaluated factors which might influence the course of the disease. The study included a group of 108 asthmatics, diagnosed and monitored throughout childhood at the out-patients clinics of Oulu University Central Hospital. At the age of 20-24 yrs of age they were evaluated for the clinical state of their disease, ventilatory lung function and hyperreactivity of the airways. In the interval 30 (28%) had become totally free of symptoms, whilst 24 (22%) continued to have symptoms weekly, or more often. A quarter of the patients continued to use prophylactic medication, half still suffered from allergic rhinitis, and one third had atopic dermatitis. Skin prick tests showed at least one positive result in 86% of the patients, most often to animal danders. Ventilatory lung function tests showed forced vital capacity (FVC) to be within normal limits, but forced expiratory volume in one second (FEV1)/FVC values less than -2 SD predicted were found in 18%. Forty eight percent of the asthmatics reacted to methacholine at a dose of 0.8 mg or lower, and the degree of airway reactivity showed a significant correlation with the current attack rate. The compliance to treatment of asthma was not adequate, as one third smoked and 81% lacked proper check-ups. Concomitant atopic dermatitis, severe early disease and impaired ventilatory lung function at school age, were observed to be significant risk factors for a severe asthma outcome as a young adult. PMID- 8519376 TI - Predictive nature of bronchial responsiveness and respiratory symptoms in a one year cohort study of Sydney schoolchildren. AB - We wanted to examine the predictive nature, over one year, of bronchial hyperresponsiveness (BHR) and recent wheeze (in the previous 12 months), which are the measurements frequently used to classify asthma for epidemiology. A prospective cohort study of 236 children, aged 8-11 yrs, was undertaken, with an initial baseline study, followed by four studies at three monthly intervals over one year. At each study, we measured bronchial responsiveness to histamine by the rapid method, respiratory symptoms by parent questionnaire, and atopy by skin prick tests to common allergens. Airflometer readings, which are closely related to FEV1, were self-recorded. Baseline data were used to classify children into the four categories of "current asthma" (BHR and wheeze), "wheeze only", "BHR only", or "normal". During the year following baseline study, the group initially classified as "wheeze only" had normal Airflometer variability, and 59% had wheeze, and 33% had BHR, which tended to be mild. In the group initially classified as "BHR only", 52% had wheeze with a peak in winter, and 62% had BHR during the following year. This group had more severe bronchial responsiveness and Airflometer variability than the normal and wheeze only groups. The group initially classified as current asthma had a more severe condition, with continued BHR (100%), and wheeze (93%), increased Airflometer variability and more atopy. Thus, the natural history of bronchial responsiveness, respiratory symptoms and allergic history in this group was different from the other three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519377 TI - Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies. AB - Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519378 TI - Importance of the time interval between FEV1 measurements in a methacholine provocation test. AB - We examined the hypothesis that a forced expiratory volume in one second (FEV1) manoeuvre (and the preceding deep inhalation) before inhalation of methacholine might influence FEV1 measured after methacholine, if the time between measurements was short. Six to nine healthy subjects inhaled a single dose of methacholine, known to cause about 20% decrease in FEV1, on different days in different test protocols. If an FEV1 manoeuvre was performed immediately before methacholine, the first FEV1 measured 3 min after provocation was higher (77% of basal FEV1) than if a pre-methacholine FEV1 manoeuvre was not performed (64%). This effect of a pre-methacholine FEV1 manoeuvre was also demonstrated at 2, 4 and 6, but not at 10 min after the start of methacholine inhalation. If an FEV1 manoeuvre was not performed before methacholine, the second and subsequent FEV1 measured in constricted airways was higher than the first, and of similar magnitude to the first FEV1 in tests where a pre-challenge FEV1 manoeuvre was performed. In another trial, 10 healthy subjects performed two stepwise methacholine tests, with either 6 or 3 min between dose steps. The percentage decrease in FEV1 per mg of inhaled methacholine decreased from 2.6 (1.9-5.2) to 1.7 (0.8-2.3) (median, interquartile-range) when the time interval was shortened. The results suggest that the deep inhalation associated with the FEV1 manoeuvre decreases the bronchial tone in airways constricted by methacholine for up to 6 min, possibly due to yielding of cross-links in airway smooth muscles. PMID- 8519379 TI - Cross-tachyphylactic airway response to inhaled bradykinin, kallidin and [desArg9]-bradykinin in asthmatic subjects. AB - Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519380 TI - Cancer risk in asthmatic subjects selected from hospital discharge registry. AB - We wanted to study cancer risk in asthmatic subjects. With the use of central health registries, a cohort of 64,346 patients, treated in hospital with an asthma diagnosis, was followed with respect to cancer development. The observed numbers of different types of cancer were compared with the expected numbers, estimated from population data, with consideration taken to patient age, sex, survival, and the year of diagnosis. In general, a marked reduction of cancer incidence (2 out of 3 of the expected numbers) was found, with the exception of two cancer types: cancer of the respiratory tract and cancer of endocrine glands. A more noticeable reduction in cancer risk was seen for multiple myeloma, malignant melanoma, mammary cancer, uterine body cancer, and stomach cancer. The causes of this "protective effect" are not indicated by the present analysis, and need further study. PMID- 8519381 TI - Parenchymal emphysema measured by CT lung density correlates with lung function in patients with bullous disease. AB - In subjects with chronic obstructive pulmonary disease (COPD) computed tomographic (CT) lung density correlates with direct pathological measurements of the size of the distal airspaces, as well as with measurements of airflow limitation and impairment of the diffusing capacity. Thus, CT lung density can be used to quantify emphysema in life. We wanted to assess the use of CT scanning to detect and measure the extent of bullous lung, and to quantify the severity of emphysema in the non-bullous areas of the lungs. In patients with bullous emphysema (21 males and 2 females; aged 31-69 yrs; forced expiratory volume in one second (FEV1) 14-84% predicted; volume corrected diffusing capacity of the lungs for carbon monoxide (DLCO/VA) 17-114% predicted). CT lung density was measured in electromagnetic imaging (EMI) units. The extent of bullous emphysema correlated poorly with all respiratory function measurements. In contrast, the severity of emphysema in the non-bullous parts of the lungs, expressed as either the mean EMI number, or the EMI number of the lowest 5th percentile of the CT lung density histogram, correlated well with measurements of airflow limitation and diffusing capacity. Our findings, thus, suggest that in patients with bullae the major determinant of respiratory function is the severity of the emphysema in non-bullous lung, and that the extent of the bullae has less functional importance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519382 TI - BAL lymphocyte activation antigens and diffusing capacity are related in mild to moderate pulmonary sarcoidosis. AB - To investigate the relationship [corrected] between immunocytological features of bronchoalveolar lavage (BAL) and clinical indices in sarcoidosis, we studied the lymphocyte subsets, as well as the expression of human leucocyte antigen-DR (HLA DR) and interleukin 2 receptor (IL-2R) antigens in BAL lymphocytes. We studied 16 patients with untreated sarcoidosis and 12 control subjects. We found significantly higher absolute numbers of lymphocytes bearing the IL-2R antigen in sarcoidosis. A stronger difference between groups was observed in both the percentage and absolute numbers of HLA-DR+ lymphocytes. We also found a moderate but significant correlation between the number of lymphocytes expressing the activation antigens and single breath carbon monoxide diffusing capacity in patients with sarcoidosis: DLCO vs HLA-DR+ lymphocytes (r = -0.60); DLCO vs IL 2R+ lymphocytes (r = -0.62); carbon monoxide transfer coefficient (KCO vs HLA-DR+ lymphocytes (r = -0.53); and KCO vs IL-2R+ lymphocytes (r = -0.58). Our results suggest that the reduction in diffusing capacity, expressed as either DLCO or KCO, results from the severity of alveolitis in mild to moderate sarcoidosis. PMID- 8519383 TI - CEASE (Collaborative European Anti-Smoking Evaluation): a challenging multicentre trail organized by the European Respiratory Society. PMID- 8519384 TI - Respiratory function of the rib cage muscles. AB - Elevation of the ribs and expansion of the rib cage result from the co-ordinated action of the rib cage muscles. We wished to review the action and interaction of the rib cage muscles during ventilation. The parasternal intercostal muscles appear to play a predominant role during quiet breathing, both in humans and in anaesthetized dogs. In humans, the parasternal intercostals act in concert with the scalene muscles to expand the upper rib cage, and/or to prevent it from being drawn inward by the action of the diaphragm. The external intercostal muscles are considered to be active mainly during inspiration, and the internal intercostal muscles during expiration. The respiratory activity of the external intercostals is minimal during quiet breathing both in man and in dogs, but increases with increasing ventilation. Inspiratory activity in the external intercostals can be enhanced in anaesthetized animals and humans by inspiratory mechanical loading and by CO2 stimulation, suggesting that the external intercostals may constitute a reserve system, that may be recruited when the desired expansion of the rib cage is increased. The triangularis sterni is an important expiratory muscle during quiet breathing in animals, but it is not active during quiet breathing in man. However, during expiration below functional residual capacity (FRC), and during speech, laughing and coughing, the triangularis sterni is recruited and plays an increasingly important role. PMID- 8519385 TI - Weight loss in chronic obstructive pulmonary disease. AB - Weight loss occurs in about a third or more disabled patients with chronic obstructive pulmonary disease (COPD), and appears to be a poor prognostic factor. As such, it correlates only weakly with FEV1, transfer factor and other measures of respiratory physiology and is probably, to a certain extent, independent of them. Recent studies of basal metabolic rate (BMR) in COPD using steady-state, non-invasive calorimetry, have shown it to be elevated by 10-20% in up to 40% of such patients. It is likely that this represents true hypermetabolism per kilogram of fat free mass. An elevated BMR cannot be predicted from combinations of detailed lung function tests or arterial gases, as patients with similar physiology have differing BMRs. Thus, although an increased work of breathing is the probable explanation for some of the increase, other factors such as cytokines or possibly drug therapy almost certainly contribute. Muscle loss in weight-losing COPD appears to involve both type I and type II fibres, because of a combination of reduced calorie intake and disuse atrophy. Respiratory muscles share this fibre loss. Review of the controlled studies on nutritional supplementation in COPD suggests that an energy increase of about 30% is needed to achieve substantial weight gain and improve exercise tolerance. Fat-rich supplements have some theoretical advantages. Further work is needed particularly with regard to the determinants of the increased BMR in COPD, and the effect of longer term nutritional supplements on prognosis. PMID- 8519386 TI - Steroid resistant asthma: what is the clinical definition? AB - Asthma is usually a steroid responsive disease. A few patients respond poorly to these drugs, and others need such high doses to control the disease that side effects become a serious problem. The term steroid resistant asthma is used for both groups. In some patients, factors may be operating to make the asthma worse and, thus, to increase the requirement for steroids. In order to make a clinical diagnosis of steroid resistant asthma, it is therefore necessary to investigate the factors that could be operating to prevent a "normal" response to steroids. These factors include wrong diagnosis, insufficient steroid reaching the airway mucosa, continuing exposure to sensitizing agents, unrecognized aggravating agents, excessive use of beta-agonist aerosols, and failure to undertake regular management according to a strict management plan. Using a strict clinical definition of steroid resistant asthma leads to better investigation and treatment of individual patients, allows steroids to be stopped when they are not indicated, allows other anti-inflammatory drugs to be used with confidence, and provides a well-defined group of patients for further research relating to the mechanisms of action of steroids. PMID- 8519387 TI - Recurrent interlobar pneumothorax in an asthmatic patient. AB - We report a case of spontaneous interlobar pneumothorax, an uncommon condition. The diagnosis was suspected from the frontal chest X-ray, which showed an incompletely circumscribed air-containing space, with a fluid level. The diagnosis was confirmed by the lateral projections of standard X-ray and tomography, and by thoracic computed tomography (CT). Such air-fluid levels should not be confused with pneumatocele, cystic or cavitary diseases. PMID- 8519388 TI - Acute eosinophilic pneumonia in a heroin smoker. AB - Inhalation of heroin is known to provoke asthma. We report on the case of a patient who, after repeated inhalation of heroin, presented with decreased lung volume associated with bronchial hyperresponsiveness, diffuse pulmonary infiltrates, and bronchoalveolar lavage fluid eosinophilia. Rapid remission was obtained after heroin abstinence and initiation of corticosteroid treatment. PMID- 8519389 TI - [Cryopreserved tumor bank in the Pathology laboratory]. PMID- 8519390 TI - [Cells of the dendritic lineage are key cells in the immune response]. PMID- 8519391 TI - [Nodal histiocytic hyperplasia and proliferation]. PMID- 8519393 TI - [Digestive dendritic cells]. PMID- 8519392 TI - [Langerhans-cell histiocytosis. Recent data on diagnosis and physiopathology]. PMID- 8519394 TI - [Significance of polyglucosan bodies in neuropathology. Clinico-pathologic study of seven cases]. AB - Seven observations, having in common an accumulation of polyglucosan bodies in the nervous system, are reported. In 2 cases of adult polyglucosan body disease, characteristic polyglucosan bodies were found on the peripheral nerve biopsies, and also on the cerebral biopsy in one of these patients who was demented. The 5 other cases presented medically intractable temporal lobe epilepsy. Recovery was obtained by a temporal lobectomy in which a massive accumulation of polyglucosan bodies was discovered. These personal observations are discussed with regard to other conditions characterized by accumulation of polyglucosan bodies in the nervous system. The non specificity of these formations is emphasized. PMID- 8519395 TI - [Cutaneous candidiasis due to Candida parapsilosis occurring in the course of idiopathic aplastic anemia]. AB - Candida parapsilosis is a very common and saprophytic fungus. Its pathogenic role has been reported in intensive care units after invasive instrumentations. We report a case of dermal candidiasis due to Candida parapsilosis occurring in an immunocompromised patient suffering from aplastic anemia treated with corticosteroids. The histopathological aspect was non specific, showing a polymorphous granulomatous reaction in the middermis. Findings of periodic acid Schiff and Grocott-Gomori stains revealed a large number of pseudohyphae and spores. Candida parasilosis was cultured from a skin biopsy. The route of skin infection is discussed: direct inoculation or septic localization after fungemia. PMID- 8519396 TI - [Syringomatous carcinoma a propos of three cases with a review of the literature]. AB - Three cases of syringomatous carcinoma are reported. It is a rare adnexal neoplasm of the skin with a marked propensity for early infiltrative and locally aggressive growth. The tumor usually involves the face and particularly the upper lip. Microscopically, this tumor is characterized by syringomatous pattern and sclerotic collagenous stroma. PMID- 8519397 TI - [Aggressive angiomyxoma of the perineum and pelvis. A report of two cases with pelvic and para-testicular localization]. AB - Two cases of aggressive angiomyxoma of the pelvis and perineum are described; the first occurred in 32 year old woman who had a vulvar mass, the second in a 78 year old man who presented inguinal hernia. This recently described entity is characterized by its microscopic appearance (low cellularity, loose myxoid stroma and prominent vascular component), and propensity to local aggressivity, and common recurrence after surgery. PMID- 8519398 TI - [Slow spinal cord compression in a young adult]. PMID- 8519399 TI - [A thyroid nodule with unexpected appearance]. PMID- 8519400 TI - [Cholestasis mimicking a bile duct obstruction]. PMID- 8519401 TI - [An EDTA-pressure cooker protocol. A high performance immunohistochemistry technique]. PMID- 8519402 TI - Comparative analysis of bone stresses and strains in the Intoss dental implant with and without a flexible internal post. AB - The clinical success of any dental implant is dependent upon the maintenance of good-quality bone supporting it. Previous studies have shown high values of strain around the neck of an implant under lateral loading. These high values may lead to fatigue damage and resorption in lower strength cancellous bone. In this study, the finite element method has been used to study the bone strain distribution around the following implants: (a) an Intoss dental implant, referred to as the 'standard' implant; (b) a comparative Branemark implant and (c) a modified Intoss implant with a central flexible post, referred to as the 'modified' implant. Three different bone distributions have been investigated under axial and lateral loading: (a) implant surrounded by cortical bone; (b) implant tip supported by cortical bone with a thin layer of cancellous bone along the length and top of the implant; (c) implant tip and top supported by cortical bone with a thin layer of cancellous bone along the remaining length. For the standard implant, similar maximum equivalent strain values were predicted for the bone surrounding a comparable length Branemark-type implant. Modification of the standard implant design to include a flexible central post resulted in a decrease in the maximum von Mises stresses and equivalent strains in the cancellous bone. It is postulated that this will reduce the likelihood of bone fatigue failure and subsequent resorption in this bone. Thus the proposed design change is predicted to be highly beneficial in terms of bone load transfer. PMID- 8519403 TI - The influence of joints and soft tissue on the natural frequency of the human tibia using the impulse response method. AB - The influences of the joints adjacent to the human tibia, the surrounding soft tissue and the fibula on the vibrational parameters of the tibia (that is natural frequency, mode shape and damping ratio) are in need of clarification. Using five cadaveric human legs, the resonant frequency and damping ratio were measured with an accelerometer placed on the medial tibial condyle while the medial malleolus was impacted by an impulse hammer. The legs were subsequently dissected and the measurements were made in six conditions. The mode shape was obtained by use of modal analysis. Hammer impacts were given at 15 points along the three surfaces of the tibia, while an accelerometer was attached to the surface of the medial malleolus. Resonant frequencies ranged from 275 to 405 Hz in the intact specimens and successively increased with removal of the skin, muscles and foot, and then decreased with the removal of the femur and the fibula. Damping ratios successively decreased. The transitional pattern of natural frequencies was similar to that of the resonant frequencies. The mode shape represented the first bending mode and it corresponded to the condition of the tibia in which the proximal and distal ends of the bone were free. PMID- 8519404 TI - Forces generated in guide-wires when drilling human bone. AB - In orthopaedic surgery guide-wires are extensively used for the drilling of pilot holes in human bones to allow further drilling, reaming and screw-tapping to take place in the repair and reconstruction of fractures. The guide-wires are generally 1.5 to 2.5 mm in diameter and have a three-faceted point with or without a screw thread. This paper describes drilling tests carried out using both types of guide-wire and these are compared with results obtained from a two faceted geometry developed during this research. Tests were performed on the heads of femurs which had been removed during hip arthroplasty. A variable speed drilling machine together with a very sensitive drilling dynamometer were used for measuring the torque and thrust during the experimental stage of the research. This equipment was developed as part of an overall research programme into the mechanics of drilling of human bone. The indications are, firstly, that little advantage is gained by using a threaded-point guide-wire. In fact using a thread on the guide-wire can be a disadvantage. Secondly, the thrust cutting force is dependent on the spindle speed and feed. An optimum set of speeds of between 800 and 1400 r/min is recommended for 2.5 mm diameter guide-wires. PMID- 8519405 TI - Finite element analysis in the design and characterization of an absorbable cement restrictor. AB - The benefit of using a cement restrictor to achieve cement pressurization during total hip arthroplasty is well established. An absorbable cement restrictor design has been developed with the use of a finite element model. The non-linear axisymmetric model was used to optimize specific parameters so as to perform within acceptable limits when tested over a specified range of medullary canal sizes. The results achieved from a hybrid experimental/analytical design methodology allowed for a shorter development cycle for the initial size and each additional size in the design family thereafter. The resulting cement restrictor design was compared to and exceeded the performance of currently clinically accepted devices in resisting migration. PMID- 8519406 TI - Roentgen stereophotogrammetric analysis for assessing migration of total hip replacement femoral components. AB - A new Roentgen stereophotogrammetric analysis system, using a biplane technique, has been developed to determine the migration and rotation of total hip replacement (THR) femoral components in three dimensions. Stainless steel marker balls were injected into the femur during the operation. The patients stood within a calibration frame during the X-ray. The two exposures were taken consecutively allowing radio-opaque shutters to be moved in front of the films to prevent fogging. Studies with a model demonstrated that the system was capable of measuring the position of an implant to better than 0.11 mm (2 SD). In vivo measurements demonstrated that the migration rate of the different parts of the femoral component could be determined with an accuracy of 0.25 to 0.50 mm/year. By considering the accuracy determined in different ways, methods for improving the system have been identified. The migration and rotation rate of 58 Hinek cemented femoral components was studied for four years. Migration was three to five times greater (p < 0.001) during the first year than subsequently. The prosthesis head moved the most during the first year (0.94 mm). A better understanding of the cause of implant failure could be obtained by studying the early migration of different types of prosthesis and comparing this with their clinical results and design features. PMID- 8519407 TI - A biological basis for instantaneous centres of rotation of the vertebral column. AB - The instantaneous centre of rotation has proven to be a useful parameter of vertebral motion. The normal location of instantaneous centres has been determined in cadavers and in normal volunteers for the cervical, thoracic and lumbar spines, and abnormal location of centres has been shown to correlate with spinal pain. However, to date, an instantaneous centre has constituted no more than a convenient mathematical summary of vertebral kinematics. It has defied resolution into biologically meaningful parameters. This study offers a novel model of vertebral motion in which the instantaneous centre of rotation can be shown to be a function of the location of the centre of reaction of a vertebra, and the intrinsic rotation and translation it undergoes. These parameters are strictly linked by equations that determine the location of an axis of rotation. These equations allow aberrations in the location of an axis to be interpreted in terms of the anatomical and pathological factors that affect the centre of reaction of the vertebra and the rotation and translation it undergoes. PMID- 8519408 TI - Design of a non-constrained, non-cemented, modular, metacarpophalangeal prosthesis. AB - A non-constrained, non-cemented, modular prosthesis for replacement of the metacarpophalangeal joints of the fingers has been developed. The prosthesis is of a surface design which is modular in construction and is implanted into the bones with a press fit. The prosthesis is designed to be implanted into patients with traumatic injuries, post-traumatic osteoarthritis and into patients with rheumatoid arthritis at an early stage in the disease where the muscles and ligaments that surround the joint are still functional and can provide joint stability. PMID- 8519409 TI - Assessment of mechanical stability of a parallel wire bone transport system for use with an Ilizarov frame. AB - A novel fine wire bone transport system for use with Ilizarov frames has been used in Bristol. It uses parallel wires instead of crossed wires. Its stiffness has been tested and compared with a crossed wire construct. In its basic form it is not as stiff to bending and shear loading, however, by modification it can be made at least as stiff. A parallel wire construct does not transfix as much soft tissue as a crossed wire construct when used in the leg. This is advantageous, because soft tissue transfixion causes pain and limb swelling, which impair patient mobilization. PMID- 8519410 TI - An appraisal of the paper by O'Carrol et al. (1990). AB - The paper by O'Carrol et al. (1), which addresses the problem of an elastomeric disc indented by a spherical punch, has been evaluated. The sources of disagreement between linear elastic numerical predictions and experimental measurements noted in this paper have been critically examined in the light of finite element forecasts obtained with a package which incorporates finite elasticity effects and incompressibility. PMID- 8519411 TI - A unique spectrum of p53 mutations in B-cell chronic lymphocytic leukemia distinct from that of other lymphoid malignancies. AB - The spectrum and pattern of p53 mutations detected in 42 cases of B-cell chronic lymphocytic leukemia (B-CLL) were analyzed, and several interesting features were noted. Codon 209 in the p53 gene may be a new hot-spot for p53 mutation in B-CLL disease. Four of the 42 (10%) reported B-CLL p53 mutations occurred at codon 209 versus none in 214 cases of other lymphoid malignancies screened for p53 mutations (P = 0.0006). Transversion mutations predominated at codon 273 rather than the transition mutations that are known to occur at this CpG site. Four of six (67%) B-CLL cases had transversions at codon 273 compared with two of 17 (12%) of all other lymphoid tumors examined (P = 0.02). In addition, over 65% of the p53 mutations detected in B-CLL showed a strand bias for p53 mutations on the untranscribed DNA strand. This feature of DNA strand bias is notable in cancers of the lung, esophagus, and head and neck, which may result from high exposure to carcinogens. This spectrum of p53 mutations in B-CLL together with the high frequency of transversion mutations and DNA strand bias may implicate environmental carcinogens associated with p53 gene damage in some B-CLL patients. PMID- 8519412 TI - Mutational specificity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in the Escherichia coli lacl gene of O6-alkylguanine-DNA alkyltransferase-proficient and -deficient strains. AB - Forward mutations induced by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the lacl gene of Escherichia coli were recovered from bacteria proficient (Ogt+ Ada+) and deficient (Ogt- Ada-) in O6-alkylguanine-DNA alkyltransferase activity. A CCNU dose of 1 mM was selected for DNA sequence analysis. A total of 245 induced mutations were characterized. The mutations were almost exclusively (95%) GC-->AT transitions, indicating that CCNU-induced mutations arose in bacteria primarily from misreplication of O6-chloroethylguanine, in total agreement with results obtained for monofunctional alkylating agents. The distribution of CCNU-induced GC-->AT mutations was significantly altered by the presence of DNA alkyltransferase activity (P = 0.01). In the Ogt+ Ada+ mutational spectrum, guanines flanked on both sides by A:T base-pairs were on average 2.8 times more likely to mutate than those flanked by G:C base-pairs on at least one side. This bias disappeared in the Ogt- Ada- genetic background, thereby providing evidence that O6-chloroethylated guanines adjacent to G:C base-pairs are better targets for bacterial alkyltransferase than those not adjacent to G:C base-pairs. We recently reported a similar bias for ethyl methanesulfonate, strengthening the idea that CCNU is acting as a simple ethylating compound. In summary, this paper presents for the first time evidence that DNA repair by O6 alkylguanine-DNA alkyltransferases plays a major role in removing lesions responsible for GC-->AT transitions induced by CCNU, influencing their ultimate distribution with respect to sequence context. PMID- 8519413 TI - Characterization of novel phorbol ester- and serum-responsive sequences of the rat ornithine decarboxylase gene promoter. AB - Ornithine decarboxylase (ODC), the key regulatory enzyme in mammalian polyamine biosynthesis, is rapidly induced by mitogens and tumor promoters. We used transient expression assays and DNA-protein binding studies to examine the regulation of ODC promoter activity by phorbol esters and serum growth factors. A fragment of the ODC 5' flanking region (nt-1156 to +13) was sufficient to confer 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive expression to a luciferase reporter gene when transfected into H35 cells. However, induction by TPA was not observed in Rat2 fibroblasts, although refeeding of serum-starved Rat2 cells with fresh serum-containing medium rapidly induced a fivefold to sixfold increase in ODC promoter activity, maximal about 8 h after refeeding. Deletion analysis demonstrated that several sequences contributed to basal ODC promoter activity but that nt -92 to +13 was sufficient for induction by TPA or by serum. This sequence lacked canonical TPA-responsive elements, and an activator protein-1 (AP 1) consensus oligonucleotide failed to compete effectively for proteins binding to this region. Two of four protein complexes observed by gel-shift analysis of nt -92 to +13 were competitively inhibited by wild-type but not mutant oligonucleotides encompassing a variant cyclic AMP-response element (CRE) (ODC nt -50 to -42); however, a consensus CRE did not compete. Mutagenesis of this site demonstrated that it contributes to basal expression of the ODC promoter but not to TPA or serum responsiveness. Thus, we conclude that the proximal ODC promoter (nt -92 to +13) responds to TPA and serum stimulation in a cell-type-specific manner that is not mediated by canonical AP-1 elements. PMID- 8519414 TI - Characterization of a promoter for gamma-glutamyl transpeptidase activated in rat liver in response to aflatoxin B1 and ethoxyquin. AB - gamma-Glutamyl transpeptidase (GGT) is normally absent from adult rat hepatocytes but is induced by a range of xenobiotics, including carcinogens and chemoprotective agents. As many as six mRNA species for this enzyme have been described in both rat and mouse, with various degrees of tissue specificity. These originate from one gene and have separate promoters within alternative 5' untranslated sequences. By using a cDNA-derived sequence specific for GGT mRNA III to screen a rat genomic library, a clone that contains the promoter region for this mRNA was isolated and characterized. The transcriptional start site lay some 3.5 kb upstream from that already characterized for mRNA II in rat kidney. Luciferase activity was obtained after transfection of rat hepatoma-derived cell lines with constructs containing the putative promoter III fused to a luc reporter. Although this promoter lacks a TATA box, a sequence close to the start site that binds the transcription factor TFIID in vitro was identified. By using PCR techniques, mRNA III (homologous to both mouse III and IV) and an mRNA (IV) with homology to VI in mouse were found in ethoxyquin- and aflatoxin B1-treated rat liver and kidney as well as in a hepatoma-derived cell line. No evidence was found for a product homologous to mRNA from promoter V described in the mouse. PMID- 8519415 TI - Molecular analysis of a family of cyclin-dependent kinase inhibitor genes (p15/MTS2/INK4b and p18/INK4c) in non-small cell lung cancers. AB - Cyclin and cyclin-dependent kinase (CDK) complexes play important roles in modulating the cell cycle. The CDK inhibitors (CDKIs) inhibit the kinase activities of these complexes and block the cell cycle. The p16/multiple tumor suppressor (MTS) 1/inhibitor of CDK4 (INK4) a/CDKN2 gene, a CDKI, is frequently deleted in a variety of human cancers. Recently another CDKI gene, p15/MTS2/INK4b, was cloned and localized to within 20 kb of the p16 gene. Moreover, a third CDKI gene, named p18/INK4c and having a high degree of protein homology to p16, has now been cloned. To elucidate the importance of these CDKI genes in non-small cell lung cancers (NSCLCs), we examined DNAs from 34 NSCLC samples for alterations in these genes by Southern blot and polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) analyses. Matched control normal tissues from the same individuals were also examined. Homozygous deletions of the p15 gene were found in three cases. Furthermore, comparative PCR analysis confirmed these deletions and suggested that one additional case had an abnormality of the p15 gene. Neither rearrangements nor deletions of the p18 gene were detected. By PCR-SSCP and direct sequencing of the aberrantly migrating bands, we detected only polymorphic nucleotide substitutions in both the p15 and p18 genes. In summary, the frequency of deletions of the p15 gene was 12% (four of 34 cases), and no point mutations in the p15 gene were detected in the NSCLCs. For the p18 gene, no abnormalities were detected. A previous analysis of these NSCLC samples for p16 gene alterations revealed that the three cases with homozygous deletions of the p15 gene also have homozygous deletions of the p16 gene. PMID- 8519416 TI - Inhibition of gap junctional intercellular communication and enhancement of growth in BALB/c 3T3 cells treated with connexin43 antisense oligonucleotides. AB - Many studies have correlated reductions in gap junctional intercellular communication (GJIC) with altered cellular growth, tumor promotion, and neoplastic transformation. To test directly whether reduced GJIC affects cellular growth, GJIC was inhibited in murine BALB/c 3T3 fibroblasts by treatment with a phosphorothioate-modified antisense oligonucleotide targeted against the connexin43 translation start codon, and in vitro cell growth was monitored. The cells were incubated with the oligonucleotide (0.1-0.5 microM) in liposomes in serumless culture medium for 16 h; washed and refed with serum-containing medium; and analyzed for dye-coupling, connexin43 protein and mRNA levels, and cell growth over the next 5 d. The antisense oligonucleotide inhibited dye-coupling and reduced connexin43 protein levels in a concentration-dependent manner but had no effect on connexin43 mRNA levels. Cell growth rate was not affected, but saturation density was increased approximately threefold by the oligonucleotide. These data support a role for GJIC in the establishment of contact inhibition of in vitro cell growth. PMID- 8519417 TI - Use of wild-type p53 to achieve complete treatment sensitization of tumor cells expressing endogenous mutant p53. AB - It is known that transfer of the wild-type p53 gene into p53-negative cells from transgenic mice increases their sensitivity to drug and radiation-induced apoptosis. However, unlike many human tumors, these transgenic cells do not express mutant p53, and it is not known from these earlier studies whether wild type p53 dominates the effects of mutant p53 with respect to drug and radiation sensitivity. We addressed this question in glioblastoma, a disease characterized by an unusually high level of intrinsic resistance to therapy and poor prognosis: mean survival time from diagnosis is only about 1 yr. We introduced the gene for wild-type p53 into human T98G glioblastoma cells, which express endogenous mutant p53 but not wild-type p53. Stable transfectants that co-expressed mutant and wild type p53 had enhanced sensitivity to cisplatin and gamma radiation, compared with parental cells, control vector-transduced cells, and transduced cells that had lost expression of wild-type p53. Transient wild-type p53 expression after high efficiency gene transfer by a p53 adenovirus also sensitized the cells to cisplatin and correlated with the induction of apoptosis. The sensitization effect was also observed in p53 adenovirus-infected H23 small cell lung carcinoma cells, which express endogenous mutant p53. Therefore, wild-type p53 gene transfer has dominant effects over mutant p53 in sensitizing tumor cells to therapy, which supports the potential of p53 gene therapy to enhance the efficacy of traditional therapy. PMID- 8519418 TI - High frequency of Ki-ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus. AB - Mutated ras genes have been found to be conspicuously absent from primary tumors of the esophagus, although high expression of ras p21 oncoprotein in some esophageal squamous cell carcinomas and mutations of the Ki- and Ha-ras genes in esophageal carcinoma cell lines have been reported. In this study, we found amplification of the Ki-ras gene in four of 10 esophageal adenocarcinomas (40%). No such amplification was observed among 61 squamous cell carcinomas, one pseudosarcomatous carcinoma, and eight esophageal cell lines, nor in six adenocarcinomas of the stomach. In two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki-ras proteins when compared with normal samples. This Ki-ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with the survival of the patients, or with the presence of other genetic alterations. These findings provide the first evidence for amplification of the Ki-ras gene in human esophageal cancer, which is restricted to adenocarcinomas. We also found that six of eight adenocarcinomas had point mutations in the p53 gene; this is a considerably higher prevalence than that reported for esophageal squamous cell carcinomas. These results strongly suggest that esophageal adenocarcinomas differ from squamous cell carcinomas in their molecular genetic characteristics. PMID- 8519419 TI - Infrequent Ha-ras mutations and absence of Ki-ras, N-ras, and p53 mutations in 4 nitroquinoline 1-oxide-induced rat oral lesions. AB - The alkylating agent 4-nitroquinoline 1-oxide (4-NQO) is a powerful carcinogen and induces squamous cell hyperplasia, squamous cell dysplasia, papilloma, and squamous cell carcinoma (SCC) in rat oral epithelia. Oral cancers induced by a single application of 4-NQO develop through a multistage process in a way similar to the development of this cancer in humans. In this study, mutations in exons 1 and 2 of Ki-ras, N-ras, and Ha-ras and exons 4-7 of p53 were examined by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, followed by PCR-direct sequencing for the confirmation of mutations. Samples for the mutation analysis were obtained from dysplasias, papillomas, and SCCs on the tongue epithelia induced in F344 rats by adding 4-NQO (20 ppm) to their drinking water for 8 wk. The Ha-ras mutations (61A-->T transversions in the second position) were found in five of 29 (17%) samples (one dysplasia and four SCCs). However, no mutations were detected in either Ki-ras, N-ras, or p53 under two different conditions of PCR-SSCP analysis. We suggest that some neoplasms in oral carcinogenesis induced by 4-NQO may involve Ha-ras mutations but not mutations in Ki-ras, N-ras, or p53. The 4-NQO-induced rat oral carcinogenesis model may provide a system for evaluation of the mechanisms of multistage oral carcinogenesis associated with Ha-ras mutation without Ki-ras, N-ras, or p53 mutation. PMID- 8519420 TI - Induction of karyotype instability in a murine tumor cell line by quercetin, 2 amino-1-methyl-6 phenylimidazo[4,5-b]pyridine, and okadaic acid, as revealed by transmission distortion of the inactive X chromosome. AB - Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were derived from hybrid F1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analysis using polymorphic markers on the X chromosome detected transmission distortion of the inactive X chromosome due to nondisjunction as a copy-number imbalance in allelic bands. The cells exposed to all three chemicals (but not untreated cells) exhibited such imbalances at high frequencies under exposure conditions similar to those in previous experiments in which tumor progression and recombination were observed. The cells also showed increased frequencies of tumor formation when subcutaneously injected. These results suggest that the three chemicals are capable of inducing transmission distortion of the inactive X chromosome and that such activity may be a causative factor in promoting the tumorigenicity of MST-C6 cells. PMID- 8519421 TI - The evolution of major histocompatibility class I genes in primates. AB - MHC class I genes evolve by recombination, largely within loci, and selection (presumably pathogen-driven) maintains these new alleles in the population. Although chimpanzees and humans share an A locus allelic lineage, the B locus molecules of the chimpanzee were less similar to human B locus molecules. The A and B locus molecules in rhesus and cynomolgus monkeys were even less similar to their human counterparts, with little conservation of allelic lineages between macaques and humans. In contrast to the instability of MHC class I alleles and allelic lineages, the MHC class I loci themselves are well conserved during the evolution of Great Ape and Old World primates. Homologues of HLA-A, -B, -E, and F have been found in macaques. The C locus, however, has only been found in gorillas and chimpanzees, whereas in orangutans and rhesus monkeys it is possible that the A and B loci have been duplicated. Classical New World monkey MHC class I genes are all more similar to the nonclassical HLA-G gene and a nonclassical F like gene is present in the cotton-top tamarin. Duplication and either subsequent deletion or expansion of MHC class I loci, therefore, appear to be the modus operandi of the evolution of these genes in primates. PMID- 8519422 TI - Evolution and developmental regulation of the major histocompatibility complex. AB - The ontogeny and evolution of the major histocompatibility complex (MHC) are blossoming fields that grant insight into the origins of the adaptive immune system and into the strategies adopted by particular groups of vertebrates for expression of MHC during development. This review surveys general topics concerning MHC evolution, with special emphasis on the significance of linkage of gene families within the MHC; a model is proposed in which the MHC class III region is the "primordial immune complex" with its members giving rise to classical MHC molecules. The developmental expression of MHC, both of the classical and non-classical genes, is described in detail with a concentration on differential expression by extraembryonic tissues in mammals and by tissues in "transition" during metamorphosis in amphibians. PMID- 8519423 TI - Interleukin-1 receptor antagonist. AB - The interleukin-1 receptor antagonist (IL-1ra) is unusual in that it is the only known naturally occurring, cytokine receptor antagonist with no apparent agonist function. Over the last 5 years, since the cloning of the IL-1ra cDNA sequence, there has been intensive research on the genetics, regulation, and potential therapeutic value of this protein. The later discovery of a second form of IL-1ra in 1991 has complicated the picture. Whereas the originally described IL-1ra is predominantly glycosylated and secreted (sIL-1ra), the alternative isoform is unglycosylated and intracellular (icIL-1ra). Although the biological roles of the two forms are still open to question, IL-1ra is likely to be of great importance in the pathogenesis of both acute and chronic inflammatory diseases. A large body of evidence for this conclusion has come from animal models of inflammatory disease that respond well to administration of exogenous IL-1ra. A role for recombinant IL-1ra in the management of human disease is still under investigation. The two forms of IL-1ra are encoded by a single gene by alternative usage of two first exons. Expression of sIL-1ra and icIl-1ra is regulated by two promoters. In this review I explore the genetics of the gene encoding IL-1ra (IL-1RN) and the mechanisms of IL-1ra gene activation to produce sIL-1ra and icIL-1ra. Also, possible biological roles for these immunomodulators in health and disease are discussed. PMID- 8519424 TI - Neuronal correlates of the specification of movement direction and force in four cortical areas of the monkey. AB - Single-neuron activity was recorded in several areas of the cerebral cortex when monkeys performed a movement-precueing reaction time task. In such a task, information provided by a first signal ('preparatory signal', PS) refers to what has to be done in response to a second signal ('response signal', RS). Two monkeys were trained to rotate a handle by performing wrist flexion/extension movements while two levels of frictional resistance were applied to the manipulandum. The PS provided complete, partial or no prior information about movement direction (flexion or extension) and/or the level of the frictional force (weak or strong). Since providing partial prior information about either movement parameter shortened reaction time (RT)--RT being shorter when movement direction than movement force was precued--, as compared to the condition in which no prior information was provided, the analysis of changes in neuronal activity during the preparatory period (PP), i.e., the instructed delay between PS and RS, makes the study of the neuronal mechanism underlying the specification of movement parameters possible. The activity of 411 neurons of the primary motor (MI), premotor (PM), somatosensory (SI) and parietal (PA) cortex was recorded during task performance. Many more neurons changed selectively their activity in relation to movement direction than in relation to movement force, not only during PP, but also during RT and movement time (MT). The number of purely direction-related neurons increased, whereas the number of purely force-related neurons decreased from SI to PA, then to MI and finally to PM. During PP, selective activity changes were related only to one movement parameter, whereas during RT and MT, a large population of neurons changed its activity in relation to both movement direction and force, especially in MI. These data provide further evidence for the clustering of distinct neuronal populations responsible for programming movement direction and force. PMID- 8519425 TI - Potentiation or depression of synaptic efficacy in the dentate gyrus is determined by the relationship between the conditioned and unconditioned stimulus in a classical conditioning paradigm in rats. AB - Learning a conditioned stimulus (CS)-unconditioned stimulus (US) association is accompanied by a variety of long-lasting changes in physiology and chemistry of the synapse in the dentate gyrus. To determine the time course of synaptic modification during learning, changes in the perforant path-dentate gyrus-evoked field potentials were measured in rats performing a classical conditioning (paired tone and footshock) or pseudoconditioning (unpaired tone and footshock) task. Over the course of 4 days of training, differential changes in the evoked response were observed in the two groups. In the conditioned group, there was an increase in the slope of the excitatory postsynaptic potential (EPSP) which started after five tone-shock paired trials and lasted for more than 40 min, outlasting the training session by 20 min. In contrast, a decrease in the slope of the EPSP which commenced after training and lasted for at least 1 h was observed in the pseudoconditioned group. In both groups there was a prolonged decrease in the amplitude of the population spike. The increase in the EPSP was reduced and the duration tended to shorten over days of training in the conditioned group, whereas in the pseudoconditioned group the decrease in the EPSP tended to increase. Off-line analysis of suppression of lever-pressing for food reward during the presentation of the tone, indicated that the conditioned rats had learned the tone-footshock association. Temperature was measured in the dentate gyrus of rats undergoing an identical procedure. In both groups slight temperature increases were observed, with no difference in amplitude and time course between the groups. The differential effect of conditioning and pseudoconditioning on the evoked response and changes in temperature eliminate the possibility that effects of stress, arousal and muscular effort are the primary cause of the changes in the EPSP. The results suggest that behavioural events can exert bidirectional control of synaptic strength of entorhinal cortex inputs to the dentate gyrus and that the sign of synaptic modification is at least in part determined by the temporal relationship between these events. The data are discussed in terms of the type of neural activity that may mediate the processing of information in the dentate gyrus. PMID- 8519426 TI - The effects of ventral tegmental administration of GABAA, GABAB and NMDA receptor agonists on medial forebrain bundle self-stimulation. AB - Using a conditioned discrimination ICSS paradigm, rate-current intensity functions were determined for both reward- and nonreward-associated responding for electrical self-stimulation of the MFB following intra-VTA infusion of baclofen, muscimol and N-methyl-D,L-aspartate (NMDLA). A low dose (0.064 microgram/0.5 microliter) of the GABAB receptor agonist, baclofen, microinjected into the VTA, ipsilateral to the lateral hypothalamic stimulating electrode, resulted in a rightward shift of the ICSS curve without significantly influencing either maximal rates of operant responding for electrical brain stimulation or nonreinforced performance levels. Increases in MFB current thresholds were also evident after infusion of higher doses of baclofen (0.128, 0.26 and 0.52 microgram) into the ventral tegmentum. Intra-VTA administration of the GABAA receptor agonist, muscimol (0.006, 0.012, 0.025 and 0.05 microgram) and NMDA receptor activation by NMDLA (0.5, 1, 2 and 5 micrograms) did not affect reward thresholds; however, the low dose of muscimol and the high dose of NMDLA elicited behavioral activation resulting in reward-unrelated performance effects. These results implicate the specific involvement of the GABAB receptor in the reward neurocircuitry of the VTA. PMID- 8519427 TI - Modulation of drug-induced sensitization processes by endogenous opioid systems. AB - Behavioural sensitization involves progressive increases in behavioural responses to repeated intermittent administration of drugs of abuse. Behavioural sensitization is observed to the locomotor stimulant, rewarding and discriminative effects of a drug. These are effects which seem to be essential in the initiation, expression and maintenance of a drug-seeking behaviour. Therefore the phenomenon of behavioural sensitization may have important implications for the understanding of addictive processes. Findings given in this review demonstrate the involvement of endogenous opioid systems in the initiation of sensitized responses on the neurochemical level, i.e., within the mesolimbic dopaminergic system, as well as on the behavioural level. Specifically, it is shown that behavioural sensitization to morphine and cocaine is modulated by endogenous kappa-opioid systems. PMID- 8519428 TI - Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice. AB - Reactivity to a new environment was studied in mice, using an open-field procedure in two strains, C57BL/6By and ABP/Le, the F1 populations and the intercrosses F2 and backcross segregating populations. The analysis of the behavioral traits: peripheral and central activities, leaning, rearing and defecation in the parental strains made it possible to show that the ABP/Le strain was more reactive than C57BL/6By. In addition, the study of segregating, for four phenotypic markers, in F2 and backcross populations strongly suggested that two autosomal regions were involved in the control of open-field behavior: one in chromosomal region comprising the b locus on chromosome 4 and one in chromosomal region comprising the p locus on chromosome 7. PMID- 8519429 TI - Facilitation of learning following injection of the chondroitin sulfate proteoglycan biglycan into the vicinity of the nucleus basalis magnocellularis. AB - The aim of this study was to examine the effects of biglycan, a small chondroitin sulfate proteoglycan with neurotrophic activity, on memory and reinforcement upon unilateral injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulas were injected with biglycan and tested on the uphill avoidance task, which involves punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail-shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of substance P (SP) in a reference dosage of 0.74 pmol or biglycan (doses ranging from 1.3 to 1300.0 nmol) into the NBM region. When tested 24 h later, rats treated with SP (0.74 pmol) or biglycan (2.1 and 2.6 nmol) had significantly longer uphill latencies than vehicle (PBS) controls, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of post-trial biglycan on performance during the retention trial was performed. Furthermore, the uphill avoidance task was combined with a conditioned place preference task to assess possible reinforcing effects of biglycan. Rats were injected with either 2.6 or 130.0 nmol biglycan immediately after the training trial of the uphill task. One control group received 2.6 nmol biglycan 5 h after the trial, a second group was sham-operated. Additional groups were included which received biglycan (2.6 or 130.0 nmol), SP (0.74 pmol) or PBS after the training trial but no tail-shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519430 TI - Spatial learning impairment in aged rats: comparing between aged basal forebrain lesioned and normal aged rats. AB - Normal aged rats (26 months) displayed significant impairments in learning the Morris water maze task as compared with young adult rats (3 months). The learning deficits of aged basal forebrain (BF)-lesioned rats (26 months; ethylcholine aziridinium ion was injected into the bilateral basal forebrain at 3 months age) were more severe than those of normal aged rats. Choline acetyltransferase (ChAT) in the frontal cortex of aged BF-lesioned rats activity was significantly reduced, but not in normal aged rats which level was almost the same as that in young adult rats. Histological examination showed that cholinergic fibers (acetylcholinesterase staining) in the frontal cortex reduced in aged BF-lesioned rats, but not in normal aged rats. The number of binding sites (Bmax) for [3H]vesamicol, a ligand for the vesicular acetylcholine transporter, in the frontal cortex of normal aged rats was significantly less than that in young adult rats, while the Bmax of aged BF-lesioned rats was higher than that of normal aged rats. The levels of monoamines and their metabolites in the frontal cortex and striatum but not hippocampus of aged BF-lesioned rats were markedly reduced as compared with those of normal aged and young adult rats. These results taken together indicate that normal aged and aged BF-lesioned rats exhibit learning deficits and that the differences of the severity of spatial learning deficits between normal aged and aged BF-lesioned rats may be due to, at least in part, the different properties of cathecolaminergic, serotonergic and cholinergic dysfunctions in the discrete brain sites. PMID- 8519431 TI - From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat. AB - The development of drug taking from controlled intake to drug addiction was studied by means of an animal model. Outbred rats had continuous free access to water and drinking fluids containing different concentrations of a drug for 7-9 months. After an abstinence period of 4-9 months, the drug was offered again (retest). Previous ethological classification of each rat and changes of housing conditions were used to study the modifiability of drug taking. With ethanol and the mu-agonistic opiate etonitazene, two stages followed each other. Controlled drug intake was adjusted to situational and individual variables. Social isolation of the rats raised the intake of ethanol and opiate. Dominant rats took less drugs than subordinate ones, but, in contrast to the latter, increased drug consumption after social disturbances. The adjustment of drug taking to social variables, was accompanied by changes in the dopaminergic and GABAA-ergic neurotransmission and by altered responses to acute drug administrations. Further, place preference, associated with reinforcing stimuli was modulated by subchronic sensitization/desensitization of dopaminergic transmission. Controlled drug intake lasted for 6-8 months, after which a spontaneous increase of drug consumption was found which latently continued during abstinence periods of 1 month. In the retest after abstinence, drug intake of these rats was strongly increased compared with both their previous consumption and that of drug-naive controls. Since drug taking could no longer be modulated by gustatory, environmental or individual factors (loss of control), it was considered as addictive. Addiction appeared to be specific to the kind of the drug. It persisted for the rest of the rat's life. After long periods of abstinence, ethanol-addicted rats revealed a completely altered pattern of response to self administered alcohol compared with controlled drinkers. Their dopaminergic D1 transmission was irreversibly altered. Drug addiction only developed when the rat had free choice between water and drug-containing solutions. Long-term forced administration of ethanol or opiate, only led to physical dependence bot not to addiction. Some applications of the animal model are discussed, concerning the assessment of risk factors, the intake of drug combinations, residual neurochemical changes and concepts of treatment. PMID- 8519432 TI - The neuroethological development of food-storing memory: a case of use it, or lose it! AB - Some species of birds that scatter-hoard food e.g. marsh tits, Parus palustris, use memory to retrieve stored food. These scatter-hoarding species have a larger hippocampus relative to the rest of the telencephalon than do species that store little or no food e.g. blue tits, P. caeruleus. The difference in relative hippocampal volume arises after the young have fledged from the nest and recent work on the dual ontogeny of the hippocampus and memory in hand-raised marsh tits suggests that some aspect of memory for retrieving food (whether or not stored by the bird) can stimulate hippocampal growth in juveniles at a relatively late stage in their development. PMID- 8519433 TI - Effects of ibotenic acid lesions of the ventral striatum and the medial prefrontal cortex on ethanol consumption in the rat. AB - The purpose of this study was to to assess the effect on ethanol drinking of ibotenic acid lesions in the medial prefrontal cortex and the ventral striatum of female rats with continuous access to water and a 6% ethanol solution. Ibotenic acid infusions in the prefrontal cortex did not affect ethanol intake at any time, but a significant increase in water intake was observed on the third postoperative week. Ventral striatal lesions significantly increased ethanol intake during the first 2 postoperative weeks. On the third week consumption was not significantly different from vehicle-infused controls. Apparently, then, severe excitoxic injury to the ventral striatum is compatible with normal, or increased, intake of ethanol; in contrast, similar lesions reduce the intake of other drugs of abuse such as psychostimulants and opioids. PMID- 8519434 TI - Mesolimbic dopamine system in alcohol-preferring rats. AB - The mesolimbic dopamine system of the brain, in particular the nucleus accumbens (Acb), is long known to be involved in reward behavior. When compared with the alcohol-nonpreferring NP rats, the alcohol-preferring P rats exhibit lower dopamine (DA) levels in the Acb as well as in other forebrain areas (20). In the present study, the DA innervation density, as determined by tyrosine hydroxylase (TH) immunostaining, was found lower in the selective cingulum cortex and the shell of the Acb of the P compared with that of NP rats. These structures cluster in the medial aspect of the mesolimbic system. There were no differences in other major DA mesolimbic brain regions. The subpopulation of DA neurons in the ventral tegmental area (VTA) projecting to the Acb was found to be smaller in the P than in the NP rats, as shown by horseradish peroxidase tracing and TH immunocytochemistry double staining. However, the total number of the DA neurons in the VTA, the major mesolimbic DA center, was found to be similar in the P and NP rats. These results indicate a selective reduction of catecholaminergic innervation in the dopaminergic medial mesolimbic system in the P rats and suggest that the P and NP rat lines should be a useful model for the investigation of DA involvement in alcohol drinking as well as other reinforced behaviors. PMID- 8519435 TI - Effects of benzodiazepines on aldehyde dehydrogenase activity. AB - The reported ability of benzodiazepines to increase human erythrocyte aldehyde dehydrogenase (ALDH) activity and reverse the disulfiram-induced inhibition of ALDH was reexamined. When ALDH activity assays were carried out spectrophotometrically on a hemoglobin-free lysate of human erythrocytes with propionaldehyde as substrate, addition of diazepam (10 mumol/l) did not affect the enzyme activity. When assays were carried out on intact or hemolysed erythrocytes using high performance liquid chromatographic technique with 3,4 dihydroxyphenylacetaldehyde as substrate, no significant increase in erythrocyte ALDH activity was found in the presence of chlordiazepoxide, oxazepam, diazepam, or desmethyldiazepam in the concentration range 1-20 mumol/l. Rather, a significant decrease (about 50%) in activity was obtained when lysed cells were incubated with 20 mumol/l chlordiazepoxide. Diazepam inhibited the rat liver mitochondrial low Km ALDH activity by about 50%. Disulfiram inhibited the ALDH activity almost completely in assays on human erythrocyte or rat liver mitochondrial ALDH. The ALDH activity was not regained by the subsequent addition of diazepam, nor was the effect of disulfiram reduced when diazepam was added prior to disulfiram. In an alcoholic subject who was followed during onset of disulfiram (Antabuse) therapy, the concurrent use of diazepam did not prevent a rapid decline in blood ALDH activity. The present results suggest that benzodiazepines do not increase ALDH activity in vitro, nor interfere with the inhibition of ALDH by disulfiram. PMID- 8519436 TI - The suppressant effect of ethanol, delivered via intrahippocampal microdialysis, on the firing of local pyramidal cells in freely behaving rats. AB - Intrahippocampal microdialysis was performed on 14 freely behaving rats, and the firing of pyramidal cells within the dialysis area was recorded. In one group of rats, the microdialysis was conducted only with artificial cerebrospinal fluid (ACSF) for 2-4 h. In this control group, the recorded neurons displayed normal firing patterns. In another group, ACSF was replaced for 30-60 min with various concentrations of ethanol to deliver this drug via the microdialysis probe into the cell recording area. Ethanol at the concentration of 5% (w/v) significantly and reversibly suppressed the firing of the recorded neurons. The marked firing rate alterations were not accompanied with apparent changes in the hippocampal EEG activity or the behavior of the rats, indicating localized drug actions. These data demonstrate for the first time that in the physiologically functioning brain, ethanol exerts principally a suppressant effect on the electrical activity of hippocampal pyramidal cells. PMID- 8519437 TI - Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice. AB - The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8 10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12-16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519438 TI - Alcohol-associated acute head trauma in human subjects is associated with early deficits in serum ionized Mg and Ca. AB - Acute head trauma (AHT) (caused by motor vehicle accidents that did not produce loss of consciousness or observed brain lesions on CT scan, or falls) was found to result in early (1-8 h after injury) serum deficits in ionized magnesium (IMg2+) and ionized calcium (ICa2+) assessed with ion-selective electrodes (ISEs). Total Mg (TMg) and other electrolytes as well as serum biochemical analytes were all within the normal reference ranges. AHT patients with acute alcohol intoxication (BAC > or = 150 mg/dl) or alcohol abuse (BAC > 200 mg/dl) demonstrated deficits (15-35% less than normal) in IMg2+, but serum TMg levels were normal as were electrolytes and serum biochemical analytes. AHT patients with alcohol intoxication or alcohol abuse required hospitalization for 1-3 days prior to release, whereas AHT patients without alcohol intoxication were released in less than 24 h. The ICa2+/IMg2+ ratio, a sign of increased vascular tone and vascular reactivity, was significantly elevated in AHT patients with alcohol intoxication but not in AHT patients without alcohol intoxication or abuse. These serum divalent cation changes early after traumatic brain injury could be of considerable practicable diagnostic value in the assessment of alcohol-associated head injury. Use of ion-selective electrodes to accurately measure IMg2+ could serve as a logical basis for monitoring the response of the body to AHT. PMID- 8519439 TI - Prevention of ethanol-induced sympathetic overactivity and degeneration by dexmedetomidine. AB - The effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on rat sympathetic neurons were studied during a 12-day, heavy ethanol exposure. Adult male Wistar rats were given ethanol or isocaloric sucrose three times a day by intragastric intubation. Both acute (a single dose of 300 micrograms/kg p.o.) and chronic (100 micrograms/kg x 2 P.O. throughout the experiment) effects of dexmedetomidine were tested. The superior cervical ganglia (SCG) of the ethanol exposed, non-dexmedetomidine-treated rats showed an abnormally high overall level of tyrosine hydroxylase immunoreactivity (TH-IR) and catecholamine histofluorescence. However, a subpopulation of neurons had apparently lost their catecholamine synthetic activity, as they exhibited no TH-IR or catecholamine fluorescence. The ethanol-exposed ganglia also showed structural alterations (e.g., decreased neuronal size and increased occurrence of vacuolated neurons). In the ethanol-exposed, chronically dexmedetomidine-treated group, by contrast, the SCG exhibited TH-IR and catecholamine fluorescence intensities comparable to those seen in the control ganglia. All the structural parameters studied, as well, were at the control level in the chronically dexmedetomidine-treated group. The single dose of dexmedetomidine offered only marginal protection against the ethanol-induced alterations. These results suggest that chronic dexmedetomidine treatment may prevent ethanol-induced overactivity and degeneration of catecholaminergic neurons. PMID- 8519440 TI - Effect of S(-)- and R(+)-salsolinol on the POMC gene expression and ACTH release of an anterior pituitary cell line. AB - Tetrahydroisoquinolines (TIQs) are thought to play an important role in the process of development of alcohol dependence. Being a condensation product between the alcohol metabolite acetaldehyde and dopamine they might be involved in the balance of the opioid system as well as the reward system. Therefore, the influence of the TIQ salsolinol (SAL) on the pro-opiomelanocortin (POMC) gene expression was investigated using the ArT-20 mouse anterior pituitary tumor cell line. Our results show a significant decrease in the POMC gene expression by the S(-)-enantiomer of SAL. The basal secretion of adrenocorticotropin (ACTH) as well as the corticotropin-releasing factor (CRF)-stimulated ACTH released remained unchanged after R(+)- and S(-)-SAL treatment. Interestingly, it was clearly shown that a reduction of intracellular cAMP level occurred after the treatment of the cells with S(-)-SAL whereas R(+)-SAL did not affect the cAMP production. The obtained results suggest that S(-)-SAL is possibly involved in the establishment of the opioid deficiency in alcoholics. PMID- 8519442 TI - Dietary protein regimens and chronic ethanol administration effects on sodium- and proton-dependent solute uptake in rat intestine. AB - The effect of feeding ethanol daily for 40 days has been studied on intestinal uptake of glucose, glycine, and leucine in rats fed control, 8% protein (LP), and 30% protein (HP) diets. Na(+)-dependent uptake of glucose and glycine both at pH 7.2 and pH 5.5 was significantly depressed (p < 0.001) in ethanol or LP diet-fed animals and remained unaffected in HP-fed rats compared to the controls. But ethanol administration to protein-malnourished rats enhanced the Na(+)-linked glucose and glycine uptakes. Leucine uptake remained unaffected under these conditions. Glucose uptake remained unaltered whereas glycine uptake was reduced when ethanol was administered to rats given HP diet. In the absence of Na+, uptake of glucose, glycine, and leucine was more at acidic pH compared to that at pH 7.2 under all the experimental conditions investigated. Proton-linked uptake of solutes was unaffected by feeding ethanol, LP, or HP diet in rats. Thus, chronic ethanol feeding specifically depresses the Na(2+)-dependent uptake of glucose and glycine. Dietary protein content modifies ethanol effects on intestinal solute uptake in rats. PMID- 8519441 TI - Liver antioxidant defenses in mice fed ethanol and the AIN-76A diet. AB - The effects of chronic alcohol (EtOH) ingestion on antioxidant defenses in mice fed AIN-76A liquid diets were investigated. C57Bl/6 female mice were divided into three groups and fed the AIN-76A liquid EtOH diet containing EtOH to provide 31% of total caloric intake (TCI), the same basic diet containing EtOH to provide 35% of TCI, or an isocaloric AIN-76A liquid control diet. After 3 weeks, the mice were killed and livers were excised for biochemical analysis. Liver reduced glutathione (GSH) levels, and activities of both Mn-superoxide dismutase (SOD) and Cu/Zn-SOD were significantly decreased by both levels of EtOH. Activities of catalase and glutathione transferase (GT) were significantly increased, whereas glutathione peroxidase (GP) activity was not affected by either level of EtOH. Our previous study using the Lieber-DeCarli liquid EtOH diet caused a decline of total SOD and GP activities. The results suggest that chronic EtOH administration decreases liver antioxidant defenses; however, the mice fed the AIN-76A EtOH liquid diet can maintain a higher antioxidant defense capability than those fed Lieber-DeCarli EtOH liquid diet. PMID- 8519443 TI - Sex differences and the effects of tail pinch on ethanol drinking in Maudsley rats. AB - Voluntary consumption of 10% ethanol (EtOH) vs. water was compared in EtOH-naive, male and female Maudsley Reactive (MR) inbred rats that were exposed to either daily episodes of tail pinch (TP), or no-stress controls for 35 consecutive days. Females drank significantly more EtOH than males as measured by preference for 10% EtOH vs. water, and for intake of pure EtOH. Females exposed to TP had a higher preference for EtOH relative to controls after 21 days, but there was no difference over the entire 35 days. Males exposed to TP tended to drink more EtOH during the last week of testing relative to controls. Experiment 2 compared MR females with Maudsley Nonreactive (MNRA) females for 3 weeks in the conditions described above; TP exposure increased EtOH preference in MR, but not in MNRA, females. MR females also consumed significantly more EtOH than MNRA females. In both experiments female rats drank amounts of EtOH following a 6-week period of EtOH abstinence comparable to their preabstinence levels. The large degree of variability found in inbred MR rats has implications for developing a model for the investigation of environmental influences on the development of EtOH abuse in genetically susceptible individuals. PMID- 8519444 TI - Genetic control of alcohol deprivation effect in congenic mice. AB - Male mice of A(4R) and AKM congenic resistant strains, differing in E alpha and D loci of H-2 major histocompatibility complex (MHC) only, were tested for cross maze exploration and for behavior in unavoidable slip funnel situation. On the following 15 weeks the mice had free access to food, water, and 30% alcohol. On weeks 16-17 the individual alcohol and water intakes were measured before and after 3 days of alcohol deprivation to evaluate the alcohol deprivation effect (ADE), which is known to depend upon both genetic and environmental factors. Unlike AKMs, the A(4R)s displayed shorter latency to start cross-maze exploration, greater time of immobility, less time in avoidance attempts in the slip funnel, and demonstrated negative ADE: the short-term, postdeprivation decrease in alcohol intake. It is concluded that the ADE and some of its predictors depend upon E alpha, and/or D loci of the MHC. In the A(4R) strain, the individual correlation between the ADE and the number of immediate reentries, right, and left turns, differed significantly from zero and from the corresponding values in the AKM strain, suggesting a gene-environment interaction. PMID- 8519445 TI - Alcohol inhibits neurite extension and increases N-myc and c-myc proteins. AB - Alcohol teratogenesis may be due, in part, to inhibition of neuronal differentiation by alcohol. Because decreases in the N-myc and c-myc proteins are believed to be linked causally to neuronal differentiation, we hypothesized that alcohol would increase N-myc and c-myc proteins in undifferentiated neuronal cells and would oppose the decreases in these two proteins that normally precede differentiation. In undifferentiated LA-N-5 cultured human neuroblastoma cells, alcohol increased N-myc protein levels (178% vs. control cells) and c-myc levels (222% of control). Retinoic acid decreased N-myc and c-myc and induced neurite outgrowth (a differentiation marker). Alcohol prevented retinoic acid-elicited decreases in both myc isoforms and prevented neurite outgrowth. A significant 100% increase in c-myc and an upward trend (48%) in N-myc were observed in CA1 pyramidal neurons of the dorsal hippocampus in mouse fetuses exposed prenatally to alcohol. These data suggest that increases in N-myc and c-myc protein levels are associated with inhibition of neurite extension by alcohol. PMID- 8519446 TI - Economic analysis of needle exchange. PMID- 8519447 TI - Presentation of HIV V3 loop epitopes for enhanced antigenicity, immunogenicity and diagnostic potential. AB - OBJECTIVE: To evaluate the immunological properties of a panel of human mucin MUC1/HIV V3 loop chimeras. DESIGN: The immunodominant epitope of MUC1 (APDTR) was found to be structurally isomorphous with the tip of the principle neutralizing determinant (PND) of HIV-1 (MN) (GPGRA). A panel of 120 residue, six tandem repeat (TR) and 60 residue, three TR chimeric antigens were constructed in which the repeating MUC1 epitope is replaced by HIV-1 PND. Each 20 residue TR contains one PND epitope. The PND of HIV-1 is presented in the native beta-turn conformation at the crest of each repeating knob structure of the mucin-like protein. METHODS: The antigenicity of the chimeric antigens were compared using enzyme-linked immunosorbent assay (ELISA) and HIV-infected patient sera. Structural effects of antibody-antigen interactions were determined using surface plasmon resonance, with human monoclonal antibodies, chimeric antigens and the cyclic and linear V3 loops. Immunogenicity of three versus six TR was measured in mice. RESULTS: Nine residues of the HIV PND substituted into the mucin backbone were equivalent to the 36 residue cyclic V3 loop in ELISA. The 120 residue antigens induced high titer, immunoglobulin (Ig) M and IgG, and HIV-specific antibodies in mice. CONCLUSIONS: MUC1/V3 chimeras efficiently detect HIV-specific antibodies in patient sera. Multivalent presentation of the PND is advantageous for higher affinity antibody-antigen interactions and for inducing HIV-specific IgM and IgG antibodies. PMID- 8519448 TI - High hepatitis C viraemia and impaired antibody response in patients coinfected with HIV. AB - OBJECTIVE: To compare hepatitis C virus (HCV) load in patients infected with HCV alone and those coinfected with HIV, and to evaluate the antibody response to HCV in the case of HIV infection. DESIGN: Patients coinfected with both HCV and HIV have been shown to develop hepatic changes more rapidly, which may be due to an interaction between HCV and HIV. In a prospective study, serum samples were taken from 150 patients. METHODS: Using reverse transcription followed by polymerase chain reaction and the branched DNA assay, we detected HCV RNA in 75 patients coinfected with HIV and HCV and in 75 patients infected with HCV alone. The HIV RNA was also quantified by the branched DNA assay and the p24 antigenaemia was determined by enzyme-linked immunosorbent assay. The immune response to HCV was studied in the 150 patients by the use of third generation recombinant immunoblot assay (RIBA). RESULTS: Although a comparable number of patients had detectable HCV viraemia in both groups, HCV RNA was quantifiable in 79% of HIV-positive patients and in only 43% of HIV-negative patients (P < 10(-5)), and the mean HCV RNA level was much higher in the HIV-positive group than in the HIV-negative group (P < 10(-7)). The quantity of HCV RNA did not correlate with the CD4 count, p24 antigenaemia or HIV RNA level. The analysis of RIBA showed 14.7% indeterminate or negative results in the HIV-positive group and only 4% indeterminate results in the HIV-negative group. HIV-positive patients had reactivity to less antigen bands than HIV-negative patients (P < 10(-3)), and they had a weaker reactivity to c100, c33c and NS5 antigen bands than HIV negative patients. CONCLUSION: Our results show that in the case of HIV infection, the HCV RNA levels are strongly increased, but HCV load is not linked to the immunosuppression induced by HIV; therefore, the present data do not support the hypothesis of a direct interaction between HIV and HCV. PMID- 8519449 TI - Rolipram, a specific type IV phosphodiesterase inhibitor, is a potent inhibitor of HIV-1 replication. AB - OBJECTIVE: To determine the effects of rolipram, a specific type IV phosphodiesterase inhibitor, on tumor necrosis factor (TNF)-alpha production and HIV-1 replication. DESIGN: TNF-alpha enhances HIV-1 replication in vitro; blocking TNF-alpha and thereby inhibiting HIV-1 replication may therefore potentially delay progression of HIV disease. Pentoxifylline is a non-specific phosphodiesterase inhibitor that blocks TNF-alpha synthesis and HIV-1 replication in vitro and has been shown in preliminary clinical studies to decrease viral replication in HIV-1-infected patients. Rolipram, which selectively inhibits the predominant phosphodiesterase isoenzyme of monocytes, inhibits lipopolysaccharide (LPS)-induced TNF-alpha with 500-fold greater potency than pentoxifylline. We, therefore, hypothesized that rolipram would be a powerful inhibitor of HIV-1 replication. METHODS: The effects of rolipram and pentoxifylline on TNF-alpha production and HIV-1 replication were determined in infected and uninfected peripheral blood mononuclear cells (PBMC), in a chronically infected promonocytic cell line (U1) and in an acutely infected monocytic cell line (BT4A3.5). TNF alpha was determined by specific radioimmunoassay and HIV-1 replication was measured by p24 antigen and HIV-1 mRNA production. RESULTS: Rolipram inhibited TNF-alpha production in LPS- and phorbol myristate acetate (PMA)-stimulated PBMC and in PMA-stimulated U1 cells. Rolipram also inhibited HIV-1 replication in the U1 cell line, as well as in acutely infected PBMC and BT4A3.5 cells. Depending on the experimental conditions, rolipram was 10-600 times more potent, on a molar basis, than pentoxifylline. CONCLUSION: Rolipram is a potent inhibitor HIV-1 replication and therefore deserves further investigation as a potential therapeutic agent in the treatment of HIV-1-infected patients. PMID- 8519450 TI - Frequencies of opportunistic diseases prior to death among HIV-infected persons. Community Programs for Clinical Research on AIDS. AB - OBJECTIVES: To describe the complete history of major opportunistic events experienced by 1883 HIV-infected persons prior to and specifically within 6 months of death, and to determine whether the frequency of specific events varies according to demographic characteristics, risk behaviors or geographic location. DESIGN: Descriptive case series. METHODS: Of 6682 HIV-infected individuals enrolled in studies sponsored by the Community Programs for Clinical Research on AIDS between September 1990 and June 1994, 1883 died during follow-up. A complete history of AIDS-defining events was determined for these patients by combining medical history data obtained at the time of enrollment, new events that occurred during follow-up, and causes of death. RESULTS: The most common opportunistic AIDS-defining events these 1883 patients experienced before death were Pneumocystis carinii pneumonia (PCP; 45%), Mycobacterium avium complex (MAC; 25%), wasting syndrome (25%), bacterial pneumonia (24%), cytomegalovirus (CMV) disease (23%) and candidiasis (esophageal or pulmonary; 22%). In addition, 47% of patients experienced two or three AIDS-defining events before death, and 22% experienced four or more events. In the 6 months prior to death, 22% of patients had PCP, 21% had MAC, and 20% had CMV disease. Significant sex and ethnic differences were found: bacterial pneumonia occurred more often before death in women compared with men; fewer blacks and Latinos than whites experienced Kaposi's sarcoma (KS); and fewer blacks than whites had CMV disease before death. The percentage of patients with KS and CMV also varied by risk behavior. The frequency of 10 opportunistic diseases varied by geographic region after adjustment for demographic characteristics and risk behavior. Of note, many more patients in northeastern USA had tuberculosis and fewer had MAC. CONCLUSION: A large percentage of individuals with HIV infection experienced multiple AIDS defining opportunistic diseases before death. PCP, MAC, wasting syndrome, bacterial pneumonia, CMV disease, and candidiasis (esophageal or pulmonary) account for a substantial proportion of morbidity associated with HIV infection. More diseases varied by geographic location than by demographic characteristics or risk behavior of patients. Continued research on the etiology and prevention of these diseases and how they relate to one another should be a high priority. PMID- 8519451 TI - Herpes zoster, immunological deterioration and disease progression in HIV-1 infection. AB - OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1 seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression. PMID- 8519452 TI - Endobronchial tuberculosis in HIV-infected patients. AB - OBJECTIVE: To evaluate the presence of endobronchial tuberculosis in HIV-infected patients. METHODS: Review of the clinical records of HIV-infected patients in whom diagnostic bronchoscopy was performed because of pulmonary signs or symptoms during a 3-year period. RESULTS: Seventy bronchoscopies were performed in 59 HIV infected patients. tuberculosis was diagnosed in 25 patients, of whom six showed endobronchial tuberculosis. The most noteworthy radiological finding was mediastinal and/or hilar lymphadenopathy in five patients, occasionally associated with chest miliary infiltrates (in one), or a small pleural effusion (in two). Chest radiograph was normal in one case. The endoscopic findings were hyperaemia in five, caseating bronchial masses in four, or protrusion of extratracheal lymph nodes (broad, thickened carina and patchy bronchial lesions) in three out of the six patients. Mycobacterium tuberculosis infection was confirmed by smear and culture from bronchial aspirate, bronchoalveolar lavage or bronchial biopsies. In three cases the diagnosis was confirmed by transcarinal needle mediastinal puncture aspiration. Tuberculosis was the first opportunistic pulmonary infection in every case. The clinical course with standard treatment was satisfactory in all cases with no bronchial sequelae. CONCLUSION: Endobronchial tuberculosis may be more frequent than suspected in HIV-infected patients. Routine fibrobronchoscopy in HIV-positive patients with tuberculosis could show the true frequency of endobronchial tuberculosis. PMID- 8519453 TI - Changing incidence of HIV-induced brain lesions in Oslo, 1983-1994: effects of zidovudine treatment. AB - OBJECTIVE: To investigate the relation between HIV-induced brain lesions, zidovudine (ZDV) treatment and survival length in a well-defined population of HIV-positive patients. METHODS AND PATIENTS: Ulleval Hospital has the responsibility for treating all AIDS patients from the city of Oslo except haemophiliac patients. The patient population in this autopsy study comprised all adult AIDS patients in Oslo who were treated at our hospital and died during 1983 1994 (n = 171). This represents 86% of all adult AIDS patients from Oslo who died during the same period. Full autopsy, including neuropathological examination of the brain and spinal cord, was performed on 128 (75%) of those who died. RESULTS: No significant differences were found between autopsy and non-autopsy cases with regard to sex, age, risk groups, survival length or ZDV treatment. In the autopsy material, multinucleated giant cells (MGC) in brain tissue were found in 29 cases and diffuse damage of white matter in 52 cases. Analysis shows that ZDV (600 mg per day) reduced the incidence of these brain lesions, but only if continued until death. A second finding was an increased incidence of HIV-induced brain lesions for those with long-term survival. Together these observations may explain a substantial part of the time-trend in the incidence of MGC in Oslo. MGC were frequent (40%) during the first years of the epidemic, although survival length was short in this period. The incidence fell markedly around the time ZDV was introduced and later remained low in those using ZDV until death. The incidence of MGC has, however, increased during the later years, the new cases mainly occurring in patients who had discontinued ZDV use. CONCLUSION: If continued until death, ZDV can reduce the incidence of HIV-induced brain lesions in AIDS patients. When ZDV treatment is terminated a rapid increase occurs in the incidence of HIV encephalitis. PMID- 8519454 TI - Sexual behaviour in developing countries: implications for HIV control. AB - OBJECTIVE: To provide basic information on pre- and extramarital sex in the general population and other factors related to HIV transmission. DESIGN: Cross sectional household survey in 18 countries of the developing world, mainly in Africa and Asia. RESPONDENTS: Representative samples of 1300-6995 individuals aged 15-49 years, interviewed in 1989-1993. METHODS: Face-to-face interviewing. RESULTS: We observed a huge variability between study sites, with the proportion of men reporting sexual contact outside regular partnerships in the last year ranging from 4 to 47%. Contacts with sex workers range from 1 to 25%. Women were much less likely to report non-marital sex than men. CONCLUSIONS: This first cross-cultural attempt to examine aspects of sexual lifestyles suggests that broad generalizations about multiple-partner sexual networking in particular regions are misleading. Gender, marital status, age and a few other demographic correlates were disclosed as powerful determinants of sexual behaviour, although the strength of associations varied greatly between specific locations. Condom use was very low in most study sites. PMID- 8519455 TI - HIV infection in women: immunological markers and the influence of pregnancy. AB - OBJECTIVE: To describe the influence of pregnancy on immunological marker paths and progression of HIV-infected women. DESIGN: Analysis of prospectively collected immunological and clinical data collected on 145 women reviewed at the City Hospital, Edinburgh, between 1985 and 1992 using a two-level random-effects model that allows for within- and between-patient variance. RESULTS: There were differences between the marker paths of women according to risk activity; women who had acquired HIV via injecting drug use (in addition to heterosexual intercourse) had a higher level of absolute CD4 cells, CD4% and total lymphocytes at seroconversion than those who had acquired HIV via heterosexual intercourse alone; however, immunological markers declined more steeply after seroconversion. There was no evidence that pregnancy, either before or after HIV seroconversion had an adverse effect on marker paths of HIV disease. There was a significant association between pregnancy after HIV seroconversion and post-pregnancy changes in immunological markers: an increase in the CD4% and a decrease in CD8%. However, causality cannot be implied as pregnancy itself may be associated with considerable lifestyle changes. During pregnancy the total white blood count rose due to an increase in the number of granulocytes, whereas the total lymphocyte numbers fell. The absolute CD4 lymphocyte subset counts fell progressively but the effect was due to the fall in the total lymphocyte counts, there being no influence of pregnancy on either CD4% or CD8%. CONCLUSIONS: In asymptomatic HIV infection, changes in the absolute levels of CD4 and CD8 lymphocyte counts are primarily related to changes in the other components of the white cell count because there were no changes in CD4% and CD8%. Pregnancy itself has no adverse effect on immunological markers of HIV. PMID- 8519456 TI - Two-year follow-up of persons with HIV-1- and HIV-2-associated pulmonary tuberculosis treated with short-course chemotherapy in West Africa. AB - OBJECTIVE: To assess the response to therapy for tuberculosis using rifampicin containing short-course chemotherapy, and to compare recurrence and mortality rates in seronegative persons and those with HIV-1, HIV-2, and dual serologic reactivity in West Africa. METHODS: A cohort of 835 adult patients (167 HIV-1 positive, 143 HIV-2-positive, 243 dual-reactive, 282 HIV-negative) with smear positive pulmonary tuberculosis was followed for 2 years under programme conditions. Standard self-administered treatment was daily rifampicin and isoniazid for 6 months, and in addition pyrazinamide during the first 2 months. Outcomes evaluated were rates of completion of therapy, cure, failure of treatment, recurrence after cure, and mortality. RESULTS: HIV-positive patients had lower rates of completion of therapy (65-73%) than seronegative patients (79%), mainly because of increased mortality. Among patients completing therapy, failure of treatment was similarly low in HIV-positive (2%) and seronegative patients (1%). Recurrence rates after cure did not differ significantly in the 18 months of follow-up in the four serologic groups (3-7%). The respective mortality rates for HIV-1-positive, HIV-2-positive, and dually reactive patients were 20.3, 8.3, and 25.5 per 100 person-years (PY), compared with 2.2 per 100 PY among seronegatives. CONCLUSIONS: Rifampicin-containing short-course chemotherapy for pulmonary tuberculosis is associated with similar cure and recurrence rates in HIV-positive and HIV-negative persons completing 6 months of therapy. HIV-2 infection is associated with more favourable survival than HIV-1 infection or dual reactivity, even when AIDS-defining illness is already present. However, mortality is significantly increased in all seropositive groups compared with HIV negative tuberculosis patients; thus, establishing the causes of this increased mortality is a priority. PMID- 8519457 TI - HIV-2 transmembrane protein gp36 like HIV-1 gp41 binds to human lymphocytes and monocytes. PMID- 8519459 TI - Non-Hodgkin's lymphoma and Kaposi's sarcoma causing cavitary lung lesions in a patient with AIDS: an HIV-associated collision tumor. PMID- 8519458 TI - Evidence for an effect of human leukocyte antigens on susceptibility to Kaposi's sarcoma related to charge and peptide-binding properties of class I molecules. PMID- 8519460 TI - Tuberculous brain abscess should be considered in HIV/AIDS patients. PMID- 8519461 TI - The endoscopic brush cytology specimen in the diagnosis of intestinal microsporidiosis. PMID- 8519462 TI - Clindamycin desensitization in an AIDS patient. PMID- 8519463 TI - Exploring confounding in nested case-control studies. PMID- 8519464 TI - HIV seropositivity and cholera in refugee children from Rwanda. PMID- 8519465 TI - Marked elevation of the serum ferritin is highly specific for disseminated histoplasmosis in AIDS. PMID- 8519466 TI - The use of CD4 counts as prognostic markers in HIV infection. PMID- 8519467 TI - Statistics from the Centers for Disease Control and Prevention. PMID- 8519468 TI - Overview of microbial biofilms. AB - As the success of this two-issue special section of the Journal of Industrial Microbiology attests, the study of microbial biofilms is truly burgeoning as the uniqueness and the importance of this mode of growth is increasingly recognized. Because of its universality the biofilm concept impacts virtually all of the subdivisions of Microbiology (including Medical, Dental, Agricultural, Industrial and Environmental) and these two issues incorporate contributions from authors in all of these disciplines. Some time ago we reasoned that bacteria cannot possibly be aware (sic) of their precise location, in terms of this spectrum of anthrocentric subspecialties, and that their behavior must be dictated by a standard set of phenotypic responses to environmental conditions in what must seem to them (sic) to be a continuum of very similar aquatic ecosystems. In this overview I will, therefore, stress the common features of microbial biofilms that we should bear in mind as we use this simple universal concept to seek to understand bacterial behavior in literally hundreds of aquatic ecosystems traditionally studied by dozens of subspecies of microbiologists reared in sharply different scientific and academic conventions. PMID- 8519470 TI - Tolerance of Staphylococcus epidermidis grown from indwelling vascular catheters to antimicrobial agents. AB - During a prospective study of indwelling vascular catheter-related infections, 134 isolates of Staphylococcus epidermidis were grown from 700 catheter tips. In vitro antimicrobial susceptibility testing of these isolates to oxacillin, vancomycin and ofloxacin was performed using the standard broth microdilution technique. These results were compared to those for the same organisms grown in biofilm before the addition of antimicrobial agents. In 96-well flat bottom microtiter plates, 10(4)-10(5) colony forming units of S. epidermidis in 0.1 ml broth were grown for 18 h at 37 degrees C, at which time a biofilm was observed for all isolates. Different concentrations of antimicrobial agents (0.1 ml) were then added to the plates. The plates were incubated for 18 h at 37 degrees C. Since MICs could not be estimated in these plates, all the wells were subcultured after mixing the biofilm with the broth. Minimum bactericidal concentrations (MBCs) were defined as 99.9% reduction in colony forming units. For organisms grown in suspension, 100% of the isolates were susceptible to vancomycin, 81% to ofloxacin and 40% to oxacillin. MBCs of susceptible isolates were within four fold differences for vancomycin (53%), oxacillin (50%), and ofloxacin (51%). When grown as a biofilm, 78%, 93% and 71% of isolates had MBCs of > or = 2048 micrograms ml-1 of oxacillin, vancomycin and ofloxacin respectively. These data demonstrate the reduced bactericidal activity of antimicrobial agents against S. epidermidis in a biofilm and a simple method for its detection in the microbiology laboratory. PMID- 8519469 TI - Biofilms in device-related infections. AB - The use of various medical devices including indwelling vascular catheters, cardiac pacemakers, prosthetic heart valves, chronic ambulatory peritoneal dialysis catheters and prosthetic joints has greatly facilitated the management of serious medical and surgical illness. However, the successful development of synthetic materials and introduction of these artificial devices into various body systems has been accompanied by the ability of microorganism to adhere to these devices in the environment of biofilms that protect them from the activity of antimicrobial agents and from host defense mechanisms. A number of host, biomaterial and microbial factors are unique to the initiation, persistence and treatment failures of device-related infections. Intravascular catheters are the most common devices used in clinical practice and interactions associated with these devices are the leading cause of nosocomial bacteremias. The infections associated with these devices include insertion site infection, septic thrombophlebitis, septicemia, endocarditis and metastatic abscesses. Other important device-related infections include infections of vascular prostheses, intracardiac prostheses, total artificial hearts, indwelling urinary catheters, orthopedic prostheses, endotracheal tubes and extended wear lenses. The diagnosis and management of biofilm-associated infections remain difficult but critical issues. Appropriate antimicrobial therapy is often not effective in eradicating these infections and the removal of the device becomes necessary. Several improved diagnostic and therapeutic modalities have been reported in recent experimental studies. The clinical usefulness of these strategies remains to be determined. PMID- 8519471 TI - Bacterial biofilm and clogging of biliary stents. AB - Endoscopic biliary stenting has become a standard palliative treatment for obstructive jaundice due to malignancies of the pancreas and the hepatobiliary system. Despite the high initial success rate in achieving biliary drainage, durable endoscopic stenting has been limited by the clogging of biliary stents, usually after 4-5 months, due to formation of an adherent bacterial biofilm. Various methods have been investigated for the prevention of bacterial adhesion and prolongation of stent patency. These include: 1) prophylactic use of antimicrobial agents and bile salts; 2) testing of new stent material and new designs for these biliary stents; and 3) the recent introduction of self expandable metal stents. Each method has its own merits as well as specific problems. This article reviews the pathogenesis of biofilm formation on the biliary stents and the latest status of research in avoiding the problem of stent occlusion. PMID- 8519472 TI - Lectin-biotin assay for slime present in in situ biofilm produced by Staphylococcus epidermidis using transmission electron microscopy (TEM). AB - A lectin-biotin assay was developed for use in the specific detection of slime produced by Staphylococcus epidermidis RP62A and M187sp11 grown in a chemically defined medium. Mature biofilm was formed on polyvinylchloride (PVC) disks using a combined chemostat-modified Robbins device (MRD) model system. Specimens fixed in situ were: 1) stained with ruthenium red; 2) reacted overnight with biotin labeled lectins (WGA, succinyl-WGA, Con A, or APA) followed by treatment with gold-labeled extravidin; or 3) reacted with antibodies against S. epidermidis RP62A capsular polysaccharide/adhesin (PS/A) using an immunogold procedure. WGA and succinyl-WGA (S-WGA), which specifically bind N-acetylglucosamine, were shown by TEM to react only with slime, both cell-associated and exocellular. In contrast, Con A, APA and anti-PS/A reacted with the bacterial cell surface but did not react with slime. These results indicate the usefulness of WGA lectin as a specific marker for detection of the presence and distribution of slime matrix material in S. epidermidis biofilm. PMID- 8519474 TI - Dental plaque as a biofilm. AB - Dental plaque is the diverse microbial community found on the tooth surface embedded in a matrix of polymers of bacterial and salivary origin. Once a tooth surface is cleaned, a conditioning film of proteins and glycoproteins is adsorbed rapidly to the tooth surface. Plaque formation involves the interaction between early bacterial colonisers and this film (the acquired enamel pellicle). To facilitate colonisation of the tooth surface, some receptors on salivary molecules are only exposed to bacteria once the molecule is adsorbed to a surface. Subsequently, secondary colonisers adhere to the already attached early colonisers (co-aggregation) through specific molecular interactions. These can involve protein-protein or carbohydrate-protein (lectin) interactions, and this process contributes to determining the pattern of bacterial succession. As the biofilm develops, gradients in biologically significant factors develop, and these permit the co-existence of species that would be incompatible with each other in a homogenous environment. Dental plaque develops naturally, but it is also associated with two of the most prevalent diseases affecting industrialised societies (caries and periodontal diseases). Future strategies to control dental plaque will be targeted to interfering with the formation, structure and pattern of development of this biofilm. PMID- 8519473 TI - Pseudomonas aeruginosa biofilms: role of the alginate exopolysaccharide. AB - Pseudomonas aeruginosa synthesizes an exopolysaccharide called alginate in response to environmental conditions. Alginate serves to protect the bacteria from adversity in its surroundings and also enhances adhesion to solid surfaces. Transcription of the alginate biosynthetic genes is induced upon attachment to the substratum and this leads to increased alginate production. As a result, biofilms develop which are advantageous to the survival and growth of the bacteria. In certain circumstances, P. aeruginosa produces an alginate lyase enzyme which cleaves the polymer into short oligosaccharides. This negates the anchoring properties of the alginate and results in increased detachment of the bacteria away from the surface, allowing them to spread and colonize new sites. Thus, both alginate biosynthetic and degradative enzymes are important for the development, maintenance and spread of P. aeruginosa biofilms. PMID- 8519476 TI - Genetic analysis of adherence by oral streptococci. AB - Streptococci are one of the most successful bacterial colonizers of the human body and are major components of oral biofilms. The bacterial cells express multiple cell-surface adhesins that are responsible for the ability of streptococci to adhere to a wide range of substrates which include salivary and serous proteins, epithelial cells and other bacterial cells. Analysis of adherence-defective mutants has indicated the importance of high molecular mass wall-associated polypeptides and of enzymes catalyzing extracellular glucan polysaccharide synthesis to the adherence and accumulation of oral streptococci. The analysis of isogenic mutants of streptococci, generated through insertional inactivation (or allelic exchange), has confirmed the essential roles of specific surface polypeptides both to adhesive processes and to correct assembly of the cell wall layers. PMID- 8519477 TI - Isolation and characterization of coaggregation-defective (Cog-) mutants of Streptococcus gordonii DL1 (Challis). AB - Streptococcus gordonii DL1 (Challis) bears coaggregation-mediating surface adhesins which recognize galactoside-containing surface polysaccharides on Streptococcus oralis 34, Streptococcus oralis C104, and Streptococcus SM PK509. Fifty-nine spontaneously-occurring coaggregation-defective (Cog-) mutants of S. gordonii DL1 unable to coaggregate with partner streptococci were isolated. Six representative Cog- mutants were characterized by their coaggregation properties with four Actinomyces naeslundii strains (T14V, PK947, PK606, PK984), Veillonella atypica PK1910, and Propionibacterium acnes PK93. The six representative Cog- mutants showed altered coaggregation with their streptococcal partners, A. naeslundii PK947, and P. acnes PK93. Based on the coaggregation phenotypes of these mutants, a model for the lactose-inhibitable coaggregation between S. gordonii DL1 and its partner bacteria is proposed. The potential use of these mutants in studies of oral biofilms is discussed. PMID- 8519475 TI - Adhesin receptors of human oral bacteria and modeling of putative adhesin-binding domains. AB - Adherence by bacteria to a surface is critical to their survival in the human oral cavity. Many types of molecules are present in the saliva and serous exudates that form the acquired pellicle, a coating on the tooth surface, and serve as receptor molecules for adherent bacteria. The primary colonizing bacteria utilize adhesins to adhere to specific pellicle receptor molecules, then may adhere to other primary colonizers via adhesins, or may present receptor molecules to be utilized by secondary colonizing species. The most common primary colonizing bacteria are streptococci, and six streptococcal cell wall polysaccharide receptor molecules have been structurally characterized. A comparison of the putative adhesin disaccharide-binding regions of the six polysaccharides suggests three groups. A representative of each group was modeled in molecular dynamics simulations. In each case it was found that a loop formed between the galactofuranose beta (Galf beta) and an oxygen of the nearest phosphate group on the reducing side of the Galf beta, that this loop was stabilized by hydrogen bonds, and that within each loop resides the putative disaccharide-binding domain. PMID- 8519478 TI - Oxygen metabolism, oxidative stress and acid-base physiology of dental plaque biofilms. AB - Dental plaque is a natural biofilm which has been a focus of attention for many years because of its known roles in caries and periodontal diseases. Acid production by plaque bacteria leads to the erosion of tooth mineral in caries, and the cariogenicity of plaque is related to population levels of acid-tolerant organisms such as mutans streptococci. However, the biofilm character of plaque allows for survival of a diverse flora, including less acid-tolerant organisms, some of which can produce ammonia from arginine or urea to counter acidification. Plaque is often considered to be relatively anaerobic. However, evidence is presented here that both supragingival and subgingival plaque have active oxygen metabolism and that plaque bacteria, including anaerobes, have developed defenses against oxidative stress. Even in subgingival plaque associated with periodontitis, measured residual oxygen levels are sufficient to allow for oxygen metabolism by organisms considered to be extremely anaerobic such as Treponema denticola, which metabolizes oxygen by means of NADH oxidases and produces the protective enzymes superoxide dismutase and NADH peroxidase. The finding that plaque bacteria produce a variety of protective enzymes is a good indicator that oxidative stress is a part of their everyday life. The biofilm character of plaque allows for population diversity and coexistence of aerobes, anaerobes and microaerophiles. Overall, agents that affect oxidative metabolism offer possibilities for reducing the pathogenic activities of plaque. PMID- 8519479 TI - Interactions of Candida albicans with bacteria and salivary molecules in oral biofilms. AB - The yeast Candida albicans coaggregates with a variety of streptococcal species, an interaction that may promote oral colonization by yeast cells. C. albicans and Candida tropicalis are the yeasts most frequently isolated from the human oral cavity and our data demonstrate that both these species bind to Streptococcus gordonii NCTC 7869 while two other Candida species (Candida krusei and Candida kefyr) do not. Adherence of C. albicans was greatest when the yeast had been grown at 30 degrees C to mid-exponential growth phase. For 21 strains of C. albicans there was a positive correlation between the ability to adhere to S. gordonii and adherence to experimental salivary pellicle. Whole saliva either stimulated or slightly inhibited adherence of C. albicans to S. gordonii depending on the streptococcal growth conditions. The results suggest that the major salivary adhesins and coaggregation adhesins of C. albicans are co expressed. PMID- 8519481 TI - Influences on the antimicrobial activity of surface-adsorbed nisin. AB - The efficacy of the antimicrobial peptide nisin was examined after adsorption to silica surfaces. Three protocols were used to evaluate nisin's activity against adhered cells of Listeria monocytogenes: bioassay using Pediococcus pentosaceous FBB 61-2 as the sensitive indicator strain; visualization and enumeration of cells by microscopic image analysis; and viability of adhered cells as determined by lodonitrotetrazolium violet uptake and crystallization. The activity of adsorbed nisin was highly dependent upon conditions of adsorption. The highest antimicrobial activity of adsorbed nisin occurred with high concentrations of nisin (1.0 mg ml-1) and brief contact times (1 h) on surfaces of low hydrophobicity. Sequential adsorption of a second protein (beta-lactoglobulin or bovine serum albumin) onto surfaces consistently resulted in decreased nisin activity. These data provide direction for the development of applications to limit microbial attachment on food contact surfaces through the use of adsorbed antimicrobial peptides. PMID- 8519482 TI - The effect of electrical currents and tobramycin on Pseudomonas aeruginosa biofilms. AB - The combined use of antibiotics with low levels of electrical current has been reported to be more effective in controlling biofilms (the bioelectric effect) than antibiotics alone. An electrical colonisation cell was designed to study the effect of antibiotics on biofilms formed on a dialysis membrane away from the electrode surface. To avoid the electrochemical generation of toxic products, Pseudomonas aeruginosa biofilms were formed in minimal salts medium that excluded chloride-containing compounds. Under these conditions, electrical currents of up to 20 mA cm-2 did not prevent biofilm formation or have any detrimental effect on an established biofilm. Tobramycin alone at concentrations of 10 micrograms ml-1 did not affect the biofilm, but were significantly enhanced by 9 mA cm-2. The effect of tobramycin concentrations of 25 micrograms ml-1 were enhanced by a 15 mA cm-2 electrical current. In both cases higher levels of electrical current, up to 20 mA cm-2, did not further enhance the effect of the antibiotic. The possible mechanisms of action of the bioelectric effect have been reported to involve electrophoresis, iontophoresis and electroporesis, thus overcoming the biofilm biomass and cell wall barriers. Our results suggest that other factors may also be important, such as the metabolic activity and growth rate of the bacteria. Such factors may be critical in maximising antibiotic efficacy. PMID- 8519480 TI - Colonization factors of diarrheagenic E. coli and their intestinal receptors. AB - While Escherichia coli is common as a commensal organism in the distal ileum and colon, the presence of colonization factors (CF) on pathogenic strains of E. coli facilitates attachment of the organism to intestinal receptor molecules in a species- and tissue-specific fashion. After the initial adherence, colonization occurs, and the involvement of additional virulence determinants leads to illness. Enterotoxigenic E. coli (ETEC) is the most extensively studied of the five categories of E. coli that cause diarrheal disease, and has the greatest impact on health worldwide. ETEC can be isolated from domestic animals and humans. The biochemistry, genetics, epidemiology, antigenic characteristics, and cell and receptor binding properties of ETEC have been extensively described. Another major category, enteropathogenic E. coli (EPEC), has virulence mechanisms, primarily effacement and cytoskeletal rearrangement of intestinal brush borders, that are distinct from ETEC. An EPEC CF receptor has been purified and characterized as a sialidated transmembrane glycoprotein complex directly attached to actin, thereby associating CF-binding with host-cell response. Three additional categories of E. coli diarrheal disease, their colonization factors and their host cell receptors, are discussed. It appears that biofilms exist in the intestine in a manner similar to oral bacterial biofilms, and that E. coli is part of these biofilms as both commensals and pathogens. PMID- 8519483 TI - Bacterial adhesion measurements on soft contact lenses using a Modified Vortex Device and a Modified Robbins Device. AB - S. marcescens 8100 and P. aeruginosa 15442 were used to study bacterial adhesion to hydrogel contact lenses which had not been worn. Bacterial removal from unworn lens materials was assessed with a calibrated vortex device modified with a digital rpm readout and fitted with a test tube attachment (MVD). The MVD, which relies on a whirlpool-like force to remove the bacteria, showed that bacteria adhered to the same degree to etafilcon A, vifilcon A and polymacon lenses under standardized conditions. Tracking the isoenzyme patterns of these bacterial species over time showed instability of S. marcescens upon repeated passage. This instability was not evident with P. aeruginosa. Bacterial adhesion of P. aeruginosa 15442, to human worn and unworn etafilcon A materials was determined with a Modified Robbins Device. The MRD was closed off at both ends stopping medium and bacterial movement after 1 h of fluid flow over the lens surface. The results show that immediately following this 1-h period more bacteria adhere to unworn contact lenses than to worn lenses. However, bacterial counts were equivalent on worn and unworn lenses following 5 h of static incubation. PMID- 8519485 TI - The effect of vitamin E deficiency on the plasticity of cholinergic synapses: a computer-assisted morphometric study. AB - A computer-assisted morphometric study has been carried out on the ultrastructural features of the cholinergic synaptic junctional areas in the dentate gyrus supragranular layer of 11-month-old female Wistar rats and in littermates fed a vitamin E deficient diet for 10 months. The number of synapses/micro m(3) (numerical density: Nv), the average area of the junctional zones (S) and the total synaptic contact area/micro m(3) (surface density: Sv) were the three parameters taken into account. Nv and Sv significantly decreased, while S increased in the vitamin E deficient group. A size distribution of S showed that while in the normally fed animals the percentage of an enlarged synapses (0.16 micro m(2)>) accounts for 19% of the whole population, in the vitamin E deficient rats it raises at 44%. Relating the number of synapses to the number of dentate gyrus granule cells, the synapse-to-neurone ratio appeared to be decreased by 30% in the vitamin E deficient animals. It is currently reported that number (Nv) and size (S) of the synapses are in a close inverse relationship which aims at maintaining constant the total synaptic surface area (Sv) in a discrete volume of the neuropil, therefore, taken together per experimental group of rats, these parameters represent a reliable index of the synaptic morphological plasticity. Our present findings clearly document that the structural dynamics of the hippocampal cholinergic synapses are markedly affected by the absence of vitamin E from the diet and, in turn, support that an increased peroxidative stress may play a central role in the widely reported vulnerability of the cholinergic terminals with advancing age. PMID- 8519484 TI - Influence of lactobacilli on the adhesion of Staphylococcus aureus and Candida albicans to fibers and epithelial cells. AB - The ability of organisms to adhere to and form biofilms on fibrous materials is believed to be an important initiating step in the induction of several diseases, such as toxic shock syndrome. Using an in vitro assay, a moderately hydrophobic strain of Staphylococcus aureus (water contact angle 35 degrees) and a hydrophilic Candida albicans (shown by a hexadecane test) were highly adherent to commercial diaper fibers. The lumen side of the diaper was porous and the fibers were very hydrophobic (> 140 degrees), but the internal section was very hydrophilic (0 degrees), presumably for lus strains was present. Surfaces precoated with lactobacilli inhibited staphylococcal adhesion by 26-97%, and candida by 0-67%. When the lactobacilli were used to challenge adherent pathogens, there was 99% displacement of the S. aureus and up to 91% displacement of C. albicans. Hydrophobic L. acidophilus 76 (54 degrees) and T-13 (80 degrees) were the most effective of five Lactobacillus isolates tested at interference by precoating. The moderately hydrophilic L. casei var rhamnosus GR-1 (33 degrees) was the most effective at displacing the yeast. Experiments with uroepithelial cells also showed that the lactobacilli could significantly interfere with the adhesion of both pathogens to the cells. The results demonstrate the rapidity with which two pathogens adhered to fibers and epithelial cells, and raised the possibility that members of the normal female urogenital flora might interfere with infections caused by these organisms. PMID- 8519486 TI - Prevention of ischemia-reperfusion damage with polymerized superoxide dismutase. AB - The efficacy of preventing ischemia-reperfusion damage by employing native or modified (mPEG-SOD) superoxide dismutase in an experimental model of acute ischemia was tested in the left hind limb of 43 Wistar rats. A significative difference (p=0.004) of the survival leg rate was found in the group treated with mPEG-SOD (86.6%) compared with the control group (30%). This difference was confirmed both clinically and by TEM analysis of muscular specimens. PMID- 8519487 TI - Hormonal changes in male subjects over-ninety. AB - The physiology of aging in very old people is still poorly understood. A wide variety of age-related factors confuse the interpretation of existing data, especially as regards the modifications of the endocrine system. The effect of age on the gonad-hypophyseal function was studied in 26 over ninety-year-old males and compared with a control aged between 27 and 88, subdivided into age groups. The serum levels of total testosterone were stable up to the ninth decade while they were lower in the over ninety-year-olds; free testosterone and its peripheral metabolites (estrogens and dehydrotestosterone) were also lower in the over ninety-year-olds with respect to the others, although the decrease had started more gradually at about the fourth decade. Sex-hormone-binding-globulin, the main serum carrier of testosterone, increased gradually with age. The levels of hypophyseal gonadotropins were constant up to the ninth decade where a significant and abrupt increase was observed. The data suggest the presence of marked alterations of the testicular-hypophyseal axis in the later decades of life, with important repercussions on the pattern of circulating sex steroids. PMID- 8519488 TI - Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA R) in acute myeloid leukemia cells. AB - The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells. PMID- 8519489 TI - Preliminary histoenzymatic muscular evaluations after ischemia-reperfusion damage. AB - The aim of this study was to evaluate the muscular regenerative properties after an induced ischemia/reperfusion injury of 4 hours and 30 min. of the left hind limb of the rat and to evaluate and compare the efficacy of native and modified polyethylene glycol superoxide dismutase (SOD and mPEG-SOD). In particular, we try to find a suitable method to study the histological and histoenzymatic properties of muscular fibres, focusing also the technical procedure employed to evaluate the new activated motor end-plates. Biopsies from flexor digitorum superficialis were collected immediately after the ischemia/reperfusion damage and also at 4th, 6th and 10th days. The adopted protocol showed a good reliability both for the necrosis and the regenerative process evaluations. However the assessment of regenerative and reinnervative processes will be completed by histomorphometric analysis. PMID- 8519490 TI - Expression of phosphotyrosine in squamous cell carcinoma of the oral mucosa. Preliminary study. AB - Phosphotyrosine (pTyr) is the product of activation of Epidermal Growth Factor receptor (EGFr) in normal and neoplastic oral keratinocytes. As previous studies revealed that EGFr expression may vary with differentiation in several squamous cell carcinomas (SCC), we investigated the expression of pTyr in 30 cases of oral SCC in which EGFr-immunoreactivity had been previously studied. This study was carried out with monoclonal antibodies using an immunohistochemical APAAP method on formalin-fixed, paraffin-embedded samples. The results of this study show that pTyr is expressed in all cases of oral SCC and that its expression is not correlated with tumor differentiation. The Authors suggest that the mechanism of EGFr-mediated cell differentiation and mitosis might short-circuit EGFr in some instances and lead to the phosphorilation of Tyrosine, probably following the stimulation by other factors. This hypothesis needs to be confirmed by appropriate studies on the dynamic biology of oral squamous cells. PMID- 8519491 TI - The multiplicity of enzymatic DNA reduction: a new purification procedure for a DHA reducing protein from potato tubers. AB - The multiplicity of DHA reducing proteins has been observed by means of a native PAGE technique in several plant species, thus demonstrating, in accordance with recent literature, that several differently evolved proteins are likely to perform DHA reduction. Moreover, a research strategy coupling the use of native PAGE with chromatographic separation procedure, tentatively performed in Solanum tuberosum, proved to be a useful tool for the separation and partial identification of the proteins involved in DHA reduction. PMID- 8519492 TI - A method of reducing the population of thymic macrophages in rats. PMID- 8519493 TI - The structure of spongious trabeculae in relation to age in man. AB - In various bones from 40-50 year old men, numerous osteons were found in spongy trabeculae. As the bones examined are subjected to different mechanical loads, and, in all samples, the osteon frequency appeared to increase with the increase in the trabecular thickness, the endotrabecular osteons was supposed to improve the deep-seated cell metabolism. Because the architecture of the spongiosa changes with age, we studied the endotrabecular osteons in the same bone but in individuals of different age. Human femurs from the collection of our Institute were divided into three groups, corresponding to the 3rd, 5th, and 7th decade of life. Trabeculae were dissected from the proximal end in correspondence of the head, lateral and medial arrangement of the neck. On the serially transverse section the thickness of trabecular tracts with or without osteons, the distance of the deep-seated osteocytes from filtering surfaces, and the orientation of the collagen fibres have been analysed. The mean thickness of the trabeculae decreases with age in the head and lateral arrangement but not in the medial one. The trabecular tracts with osteons are, on the average, significantly thicker than those without them. Almost all endotrabecular osteons show alternate lamellae, notwithstanding that the trabeculae examined are subjected to different type of mechanical forces. These findings would confirm our previous hypothesis that the presence of osteons in the trabeculae responds to metabolic request rather than to mechanical one. PMID- 8519494 TI - Morphofunctional characterization of lymphokine activated killer (LAK) cells in vitro. AB - In order to characterize the cellular subsets of peripheral blood lymphocytes cultured with interleukin-2 (IL-2), a study in vitro was developed. Both conditioned medium from PHA-stimulated lymphocytes and recombinant IL-2 (rIL-2) were employed. The following aspects were examined: the morphological pattern of IL-2 stimulated lymphocytes; the ability of these cells to recognize, bind, attack and destroy tumoral lines; their cytochemical and immunological (CD) feature. The results suggest that, in our experimental conditions, these cells showed a characteristic "hand mirror shape", cytotoxic antitumor activity, lack of hydrolytic enzymes and CD3+, CD4+ phenotype. PMID- 8519496 TI - Specificity of the zinc-iodide-osmium (ZIO) reagent in the nervous tissue: evaluation of the Ca++ binding sites hypothesis. AB - We tested the Ca(2+) binding sites detection hypothesis of the zinc-iodide-osmium (ZIO) staining on synaptic vesicles of rat cerebellar glomerulus using three different approaches based on the previous observation that Ca(2+) chelator EGTA can impede the staining reaction: (a) ZIO staining of "en bloc" tissue samples after EGTA exposure, (b) staining of ultrathin sections with ZIO reagent after EGTA treatment, (c) ZIO staining of isolated synaptic vesicles, preincubated in calcium ionophore A23187. The results of our investigation do not support the hypothesis. We conclude that ZIO staining can be referred to different molecules located mainly in secretory organelles. PMID- 8519495 TI - Oxidative modification of proteins in chronic alcoholics. AB - Oxidative modification of proteins is of great importance because of their biological role in transport, enzyme activity, immune response and membrane fluidity. This study investigated the redox status of proteins in plasma, erythrocyte and erythrocyte ghosts of chronic alcoholics; a comparison with subjects affected by chronic viral hepatitis and healthy controls was also performed. Compared to the other groups, chronic active alcoholics showed significant increase of plasma, erythrocyte and erythrocyte ghost concentrations of carbonyl proteins, marker of protein oxidative damage. Also, a significant correlation was noted between daily alcohol intake and plasma levels of carbonyl proteins. The incubation of fresh human plasma with acetaldehyde, but not with ethanol, led to a significant increase of the carbonyl protein production. In conclusion, plasma, erythrocyte and membrane proteins are oxidatively modified in active chronic alcoholics; these changes seem to be related to acetaldehyde rather than ethanol toxicity. PMID- 8519497 TI - Presence of neuroreceptors in normal and diseased temporo-mandibular joints. AB - An immunohistochemical study was performed on the articular disk and periarticular tissues of the temporo-mandibular joint (TMJ) in order to ascertain the presence of neuroreceptors (NRec) in these sites. The study was carried out with the APAAP technique on tissue samples obtained from 10 subjects without known TMJ disease and from 5 patients with severe TMJ arthritis or arthrosis. The antibodies used were directed against the following antigens: Gliofibrillary Acidic Protein (GFAP), Leu-7, Myelin Basic Protein (MBP), Neurofilaments 68 kD (NF), Neuron Specific Enolase (NSE), S-100 protein (S-100) and Synaptophysin (SYN). This study revealed that Ruffini's-like, Pacini's-like and Golgi's-like receptors can be demonstrated in TMJ periarticular tissues and that free nervous endings are present in the subsynovial but not within the articular disk. In the latter, elongated cytoplasmic processes of chondrocytes demonstrated strong S-100 immunoreactivity but they were unreactive with all other antibodies. These cytoplasmic processes were more abundant and thicker in the samples obtained from patients with diseased TMJ. The results of this study confirm that different NRec are detectable in TMJ periarticular tissues but they are absent within the articular disk. In the latter site, only chondrocytic processes are evident, especially in diseased TMJ, and they might have been confused with nervous endings in previous morphological studies. Nevertheless the absence of immunoreactivity for NF, NSE and SYN proves that they are not of neural origin. PMID- 8519498 TI - Effects of moderate doses of ethyl alcohol on cerebral lateralization of language and on hand movements. I: A dual-task paradigm study. AB - Cerebral lateralization for linguistic functions has been assessed by means of a dual-task, verbal-manual, paradigm (finger tapping) in 16 monolingual right handed non-alcoholic adult male subjects after the administration of a moderate dose of ethyl alcohol (0.6 g/kg; alcoholemia > 80 mg/dl). No significant modification of hemispheric asymmetries for linguistic functions was found. Moreover, ethyl alcohol tended to affect right-hand motor function during silent tapping, while leaving left-hand performance almost unchanged. PMID- 8519499 TI - In vitro cytolytic activity of human NK cells against osteosarcoma cell lines. AB - NK lymphocytes present CD16, CD56 and lack CD3 surface molecules and are able to spontaneously lyse tumor or virus infected cells. In this study we evaluated the susceptibility of some human osteosarcoma cell lines to NK cytolytic activity and standardized the assay conditions. NK lymphocytes were used as effector cells in a cytotoxicity test against HOS, U-2 OS and Saos-2 osteosarcoma targets. While HOS cells were susceptible on the contrary U-2 OS and Saos-2 were osteosarcoma resistant lines. Our preliminary results support a model for the study of a possible interaction between the immune system and these tumors. PMID- 8519500 TI - Effects of proanthocyanidin on normal and reinnervated rat muscle. AB - Proanthocyanidin-A2, a catechic dimer extracted from the bark of Aesculus hippocastanum L., was tested on peripheral nerve regeneration. Reinnervation of EDL and soleus muscles following traumatic nerve damage was investigated in rats by using "in vivo" tension recording technique. Muscle contraction force (twitch and tetanus), the number of motor units and the time course of twitch (time to peak and half relaxation time), were observed. The results obtained do not show that the time course of EDL and soleus muscles reinnervation is different in Proanthocyanidin-A2-treated rats in comparison to control animals. On the contrary, results point out an increase in EDL and soleus muscle mass, both in denervated and in undenervated treated rats compared to corresponding controls. Moreover, consistently with this finding, an increase in their contraction force was found. These data show that Proanthocyanidin-A2 exerts a trophic effect on muscle. PMID- 8519501 TI - Can breast cancer be prevented by dietary and lifestyle changes? PMID- 8519502 TI - Monoamine oxidase and behaviour. PMID- 8519503 TI - The molecular basis of hereditary skeletal disorders. PMID- 8519504 TI - Differences in lipolysis between human subcutaneous and omental adipose tissues. AB - Hydrolysis of triglycerides to fatty acids and glycerol in fat cells (lipolysis) is of importance for the control of lipid and carbohydrate metabolism. This process is regulated by several hormones and parahormones acting on cyclic AMP formation or breakdown, which in turn influences the activity of hormone sensitive lipase. The latter enzyme stimulates hydrolysis of triglycerides in fat cells. It is well established through in vivo and in vitro investigations that there are regional variations in the lipolytic activity of human adipose tissue. The rate of lipolysis is low in the subcutaneous femoral/gluteal region, intermediate in the subcutaneous abdominal region and high in the visceral (i.e. omental) region. In non-obese subjects the differences between the subcutaneous and visceral fat depots may be explained by site variations in the function of receptors for insulin, catecholamines and adenosine. The lipolytic beta 1 and beta 2 adrenoceptors, as well as the newly discovered beta 3, are most active in the visceral fat cells. The antilipolytic insulin receptors, alpha 2 adrenoceptors and adenosine receptors are most active in the subcutaneous fat cells. In subjects with upper-body obesity the regional variations in the action of catecholamines on lipolysis are further enhanced. Decreased action of beta 2 adrenergic receptors and increased activity of alpha 2-adrenergic adrenoceptors in combination with defects in hormone sensitive lipase function inhibits the lipolytic effect of catecholamines in subcutaneous fat cells whereas increased activity of beta 3-adrenergic receptors and decreased activity of alpha 2 adrenoceptors augment the lipolytic response in visceral fat cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519505 TI - Molecular pharmacology of alpha 2-adrenoceptor subtypes. AB - alpha 2-adrenergic receptors mediate many of the physiological actions of the endogenous catecholamines adrenaline and noradrenaline, and are targets of several therapeutic agents. alpha 2-adrenoceptor agonists are currently used as antihypertensives and as veterinary sedative anaesthetics. They are also used in humans as adjuncts to anaesthesia, as spinal analgesics, and to treat opioid, nicotine and alcohol dependence and withdrawal. Three human alpha 2-adrenoceptor subtype genes have been cloned and designated alpha 2-C10, alpha 2-C4, and alpha 2-C2, according to their location on human chromosomes 10, 4 and 2. They correspond to the previously identified pharmacological receptor subtypes alpha 2A, alpha 2C and alpha 2B. The receptor proteins share only about 50% identity in their amino acid sequence, but some structurally and functionally important domains are very well conserved. The most obvious functionally important differences between the receptor subtypes are based on their different tissue distributions; e.g. the alpha 2A subtype appears to be an important modulator of noradrenergic neurotransmission in the brain. The three receptors bind most alpha 2-adrenergic drugs with similar affinities, but some compounds (e.g. oxymetazoline) are capable of discriminating between the subtypes. Clinically useful subtype selectivity cannot be achieved with currently available pharmaceutical agents. The second messenger pathways of the three receptors show many similarities, but small functional differences between the subtypes may turn out to have important pharmacological and clinical consequences. All alpha 2 adrenoceptors couple to the pertussis-toxin sensitive inhibitory G proteins Gi and G(o), but recent evidence indicates that also other G proteins may interact with alpha 2-adrenoceptors, including Gs and Gq/11. Inhibition of adenylyl cyclase activity, which results in decreased formation of cAMP, is an important consequence of alpha 2-adrenoceptor activation. Many of the physiological effects of alpha 2-adrenoceptor activation cannot, however, be explained by decreases in cAMP formation. Therefore, alternative mechanisms have been sought to account for the various effects of alpha 2-adrenoceptor activation on electrophysiologic, secretory and contractile cellular responses. Recent results obtained from studies on ion channel regulation point to the importance of calcium and potassium channels in the molecular pharmacology of alpha 2-adrenoceptors. PMID- 8519506 TI - Genetic deficiencies of complement. AB - Genetic deficiencies of proteins of the complement system are associated with diverse clinical phenotypes. These clinical manifestations vary as a function of the specific component that is missing. Molecular and cellular biological methods, coupled with more intensive clinical studies, have defined the pathophysiological basis for this set of genetic disorders. Insights into the normal function of complement and its role in immunopathology have been derived from the extensive work in this field during the past few years. PMID- 8519507 TI - Breast cancer screening in premenopausal women: current recommendations and opportunities for research. AB - The American Cancer Society recommends periodic mammography, clinical breast examination and breast self-examination beginning at age 40 years for asymptomatic women at average risk of breast cancer. Although there is substantial evidence from meta-analyses and non-randomized studies to support these recommendations, individual randomized clinical trials of breast cancer screening have not demonstrated mortality reduction in women aged 40-49 years. The opportunity to study this issue further in the United States has been diminished by the high prevalence of screening already being conducted in that population of younger women. The International Union Against Cancer, the American Cancer Society and the National Cancer Institute of the United States have convened a series of workshops and planning meetings to consider the available data and outline plans for future research. Plans are being developed to conduct a randomized trial of mammography in women younger than 50 years in multiple European sites. Successful completion of this trial may provide critical data on efficacy of breast cancer screening in younger women. PMID- 8519508 TI - Surgery for anal lesions in HIV-infected patients. AB - Anorectal manifestations are commonplace in patients with HIV infection. However, standardized or rational treatment of these conditions has not been proposed and many patients are denied adequate treatment based on fear of complications. This review looks critically at the available literature to draw conclusions about treatment, results and complications of surgery for anorectal problems in these patients. PMID- 8519509 TI - Positional cloning and the molecular basis of immunodeficiency. PMID- 8519510 TI - The circadian clock: from molecules to behaviour. AB - Circadian rhythms are a cardinal feature of living organisms. The stereotypical organization of homeostatic, endocrine and behavioural variables around the 24 hour cycle constitutes one of the most conserved attributes among species. It is now well established that circadian rhythmicity is not a learned behaviour, but is genetically transmitted and therefore subject to genetic manipulations. Recent advances in the circadian field have demonstrated that circadian oscillations are cell autonomous, that the circadian mechanism operates through a negative feedback loop and that a growing number of genes is under circadian control. Furthermore, single-gene mutations have been isolated in mammals that have profound effects on circadian behaviour. The production and mapping of one of these mutations in the mouse, an organism about which there exists a wealth of genetic information, should accelerate the elucidation of the molecular events involved in the generation of circadian rhythms in mammals. PMID- 8519511 TI - Fatty acid composition of serum lipid fractions in relation to gender and quality of dietary fat. AB - The fatty acid compositions of serum lipid fractions are believed to reflect the quality of dietary fat, but only a few cross-sectional studies have examined these relationships in a representative free-living population. We related the composition of dietary fat obtained by 7-day food records from 84 free-living middle-aged married couples, on their habitual diets, to gas chromatographic analyses of the percentage compositions of fatty acids in three lipid fractions of fasting sera. Dietary polyunsaturated fat had Pearson's correlation coefficients of 0.63, 0.73 and 0.44 with n-6 polyunsaturated fatty acids in serum cholesteryl esters, triglycerides and phospholipids, respectively. Intake of fish showed correlations of 0.60, 0.36 and 0.52 with the percentage of eicosapentaenoate in the respective fractions. Dietary saturated fat had correlations of 0.57 and 0.54 with saturated fatty acids in serum cholesteryl esters and triglycerides, respectively. Dietary monounsaturated fat did not correlate positively with monounsaturated fatty acids in any serum lipid fraction. There were some small but significant gender differences in the serum fatty acid compositions. CONCLUSIONS: of the three serum lipid fractions, triglycerides appear to be the best reflectors of dietary polyunsaturated and saturated fat, but the intake of monounsaturated fat is poorly reflected in all serum lipid fractions. Intake of fish is mirrored in all serum lipid fractions, best in cholesteryl esters and phospholipids. PMID- 8519512 TI - Barrett's oesophagus is not a risk factor for colonic neoplasia: a case-control study. AB - Previous uncontrolled studies have suggested that patients with Barrett's oesophagus have an increased risk of colonic neoplasia. The present study was undertaken to clarify the occurrence of colorectal neoplasms in patients with Barrett's oesophagus and asymptomatic controls. Colonoscopy in 72 consecutive patients with Barrett's oesophagus and in 27 controls, none with symptoms of colonic neoplasm, revealed colorectal adenoma(s) in 17 cases (24%) in patients with Barrett's oesophagus and in eight (30%) controls. All 34 adenomas were less than 2 cm in diameter, with 30 less than 1 cm. None was malignant. Using logistic regression model with occurrence of colonic adenoma as dependent and sex, age and occurrence of Barrett's oesophagus as explanatory variables, none of these was found to be a significant risk factor for the appearance of colonic adenoma. The study thus suggests that Barrett's oesophagus is not associated with increased risk of colorectal neoplasm. Colonoscopic surveillance of patients with Barrett's oesophagus is not justified. PMID- 8519514 TI - Results of surgical treatment of stage IIIA non-small cell lung cancer. AB - From 1975 to 1993, 665 patients with non-small cell lung carcinoma (NSCLC) were studied in our Unit. Of the 55 stage IIIA patients submitted to resection, 50 were followed-up in order to evaluate the effectiveness of surgery and to identify which variables had a prognostic impact on survival. The expectancy of survival at 3,5 and 10 years was 31.7, 19.5 and 13.7%, respectively. When the analysis was limited to N2 patients, 3,5- and 10-year survival rates were 20.9, 14 and 7%, respectively. Regarding the "TN" factor, the T3N0 subset presented the highest expected survival (24.8 and 18.6% at 5 and 10 years). With regard to the "T3" factor and type of surgery, peripheral tumors submitted to en bloc resection of the chest wall showed the best 5-year survival rate (42.9%), whereas extrapleural resections--even for tumors confined to the parietal pleura--showed a 5-year survival rate of 14.3%. A slightly higher risk of death was observed in tumors originating in the superior sulcus (SST). No patients with mediastinal pleura and pericardium involvement survived more than 34 months. With univariate analysis, "N2" was the variable most significantly associated with a negative prognosis when related to T3 (T3N2 vs T3N0 0.025 < P < 0.05) or non-epidermoid tumor (no survivors at 3 years; N2 epidermoid vs N2 non-epidermoid tumor P < 0.05). Applying multivariate analysis, epidermoid cell type, even if exclusively for N2 tumors, was an independent prognostic factor, showing a favorable impact on survival expectancy (27.8% at 90 months). PMID- 8519513 TI - Results of pneumonectomy for cancer in patients with limited ventilatory function. AB - It is well established that patients with compromised pulmonary function have a greater incidence of morbidity and mortality following lung resection. The prognosis of 36 (9.7%) patients with poor respiratory function (forced expiratory volume in ls (FEV1) and FEV1/FVC (forced vital capacity) ratio were equal to or less than 50% of the predicted value) of a total of 369 patients who underwent pneumonectomy due to non-small cell lung carcinoma over 10 years were reviewed. All but three patients were male with a median age of 62.5 years. Right pneumonectomy was carried out in 12 (33%) and left in 24 (67%) patients. Median FEV1 and FEV1/FVC were 1.51 (46%) and 46.5% respectively. Three (8%) patients died within 30 days of surgery. The postoperative complication rate in patients with poor respiratory function was 44%. Nine (27%) of the hospital survivors died due to non-malignant causes (recurrent chest infection/respiratory failure) and 12 (36%) due to recurrent tumour. The cause of death in one patient was second primary lung tumour and it was unknown in three (9%) patients. Eight (24%) long term surviving patients did not have severe respiratory symptoms; their FEV1 and FEV1/FVC were remeasured and revealed a median 1.05 l (38%) and 50%, respectively of the predicted value. Actuarial 5-year survival was 29%. Poor respiratory function is associated with postoperative complications and non-malignant deaths arising secondary to respiratory failure. The survival profile demonstrates that patients were successfully treated with pneumonectomy and suggests that surgery should not be withheld from those with limited lung function if detailed investigations predict adequate residual lung function. PMID- 8519515 TI - Cardiocirculatory effects of acutely increased intracranial pressure and subsequent brain death. AB - Hemodynamic instability and functional impairment of the donor heart are currently reported problems in organ transplantation. Actual shortage of potential donor hearts continues to raise controversial discussion about adequate donor management with regard to graft quality. In an experimental open chest model, physiopathologic effects of acutely induced, irreversible intracranial hypertension (AIIHT) were investigated in situ with respect to hemodynamics, cardiac pump and muscle function, and hormonal parameters. Acutely induced irreversible intracranial hypertension was induced by rapid inflation of a subdural balloon catheter in 10 anesthetized dogs, four animals serving as controls. The observation period in both groups was 300 min. Cardiocirculatory stability was maintained by continuous crystalloid volume substitution without the use of inotropic or pressor agents. After AIIHT, three characteristic hemodynamic response phases have been observed: 1) The "acute hyperdynamic phase" lasting up to 15 min with marked increases of heart rate (HR), left ventricular pressure (LVP), cardiac output (CO) and myocardial contractility indices, 2) At the end of the "early restabilization phase", (60 min), these parameters returned close to control levels, except HR (+50%) and systemic vascular resistance (SVR) (-40%), 3) During the "late restabilization phase", filling pressures, LVP and CO remained within control limits at low SVR, contractility indices showed a decreasing tendency. All assessed plasmatic hormones (Catecholamines, triiodothyronine (T3), thyroxine (T4), adrenocorticotropic hormone (ACTH), cortisol and anti-diuretic hormone (ADH) showed a continuous fall to levels significantly below control over the phases of restabilization. Acutely induced irreversible intracranial hypertension leads to multifactorial hemodynamic and hormonal changes. At low SVR, cardiac pump function was preserved exclusively by continuous volume substitution, while myocardial contractility indicated a slight decrease. From this observed hemodynamic and functional state within the donor organism, no reliable prediction on graft functional capacity can be made. PMID- 8519516 TI - Radiographic assessment of structural defects in Bjork-Shiley convexo-concave prostheses. AB - Following the implantation of Bjork Shiley 60 degrees convexo-concave (BS-CC) prostheses, outlet strut fracture rates up to 2.5% per year have been reported. According to experimental results and clinical observations, single leg separations are regarded as the primary mechanisms leading to complete outlet strut fracture after a certain interval. In an experimental study the question was addressed, whether single leg separation can be identified by especially developed radiographic means, before outlet strut fracture occurs. Five BS-CC mitral prostheses (29-31 mm) with intentionally made single leg separations of defined gas sizes (0-75 microns) and one intact mitral prostheses were implanted in sheep in a double-blind study design. Repeat non-invasive investigations were then performed applying a recently developed fluoroscopy imaging technique with direct radiographic magnification (DIMA COR C22). Single leg separations with gap sizes of more than 25 microns were properly detected using DIMA COR C22. Separations 25 microns or less could not be detected with certainty but were evaluated as probable or possible as a result of multiple investigations. The intact prosthesis was correctly identified, but was investigated on only one occasion. Non-invasive control of Bjork-Shiley CC mitral prostheses applying especially developed direct radiographic magnification may allow for a reliable assessment of single leg separation with gap sizes of more than 25 microns in sheep. Using this technique of non-invasive serial investigations on particular patients with high probability of outlet strut fracture appears feasible, anticipating single leg separation detectability in humans. This has to be assessed in a second step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519517 TI - Aortic root replacement with a pulmonary autograft. AB - A series of 42 consecutive patients with exclusively aortic root replacement using the pulmonary autograft is presented. The mean age at operation was 19.3 years (range 0.3-41.4). Two patients died in hospital (4.8%; 70% CL: 0.0-8.2). This mortality was not related to the autograft procedure. The mean follow-up time was 30 months (range 3-70; SD: 20). Late mortality consisted of two patients; in one of these severe autograft failure occurred due to chronic juvenile rheumatoid arthritis. The estimated survival rate at 4 years was 88.8% (70% CL: 83.3-94.5). Morbidity involved three patients. One had a total heart block after operation, requiring pacemaker implantation and two patients were reoperated: one for severe autograft failure due to recurrent acute rheumatic fever and the other for severe stenosis at the distal anastomosis of the pulmonary allograft. Thromboembolic complications and endocarditis were not registered. Reoperations for technical or degenerative reasons were not necessary. The estimated event-free survival rate at 4 years was 78.7% (70% CL: 71.0-86.4). Serial echocardiography (n = 28) showed a significant increase of the autograft annulus diameter of 2.9 mm (SD: 2.7). Thirty-five of the 37 patients with an autograft in situ were in NYHA class I, and 2 in class II. At last follow up precordial color Doppler echocardiography showed moderate aortic regurgitation in one patient and no, trivial or mild aortic regurgitation in 36 patients. Stenosis of the autograft was not observed. These medium-term results are promising with respect to mortality, morbidity and functional results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519518 TI - The Ross operation: results of early experience including treatment for endocarditis. AB - The Ross operation has been performed for more than 25 years and its popularity has increased dramatically in recent years. We developed an interest in this procedure through a combination of a basic dissatisfaction with a device that requires life-long anticoagulation and the belief that a vital, autologous tissue valve with normal valve morphology and hemodynamics would prove to be superior to the mechanical valve, and that these advantages would outweigh the potential drawbacks related to the operation's technical difficulty and the risk of autograft or homograft dysfunction. From December 1992 to November 1994 40 Ross operations as total root replacements in a diverse group of patients between 5 and 72 years of age (median 32) were performed at Rigshospitalet. Seventeen (43%) of the patients had undergone at least one previous open heart operation. Eleven patients (28%) required surgery because of ongoing or previous endocarditis, and of these, nine had aortic annular destruction and cavity/pseudoaneurysm formation and five had prosthetic valve endocarditis. Three patients (8%) were operated because of mechanical valve dysfunction. One patient was treated for an ascending aortic aneurysm and aortic insufficiency. The remaining 25 patients were operated because of congenital or acquired aortic insufficiency, stenosis, or both. Ten patients (25%) underwent concomitant procedures. No mortality or serious complications occurred. Morbidity was limited to one case each of total atrioventricular (A-V) block, sternal pseudarthrosis, minor stroke, and deep vein thrombosis. Thirty-five patients had no or trivial, two patients mild, and three patients moderate autograft valve insufficiency during a median follow-up of 8 months (range 0-23 months). Two patients had pulmonary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519519 TI - Reactive thrombocytosis after coronary bypass surgery. An important risk factor. AB - Reactive thrombocytosis (RT) has earlier been reported to occur as a response to various situations and conditions, such as post-splenectomy, hematopoietic disorders, major trauma and operations, neoplasms and inflammations. In cardiac surgery the main interest has focused on thrombocytopenia that occurs after cardiopulmonary bypass (CPB) and the risk of postoperative bleeding, rather than the possibility of a late occurrence of RT as a risk factor for thrombotic complications after coronary artery bypass grafting (CABG). Between 1989 and 1992, on routine blood examinations we noticed a group of CABG patients (n = 297, Group II, 19.5%) that, 1 week after operation, showed thrombocytosis with significantly increased platelet count (521 +/- 96 x 10(3)/mm3) compared to patients with normal platelet counts (Group I, n = 1521, 185 +/- 125 x 10(3)/mm3); P < 0.001. Patient characteristics, coronary angiography findings, operative data and perioperative complications were analyzed for the two groups. There were significantly more patients with hyperlipidemia, smoking and previous myocardial infarction in Group II than in Group I; P < 0.05. Age, sex, clinical characteristics, angiography findings and operative data did not differ between the groups. There were no differences in postoperative bleeding or the need of transfusion between the groups. However, Group II (RT) patients had significantly more postoperative myocardial infarctions, 4.4% compared to 0.7% Group I; P < 0.001. Early symptomatic vein graft occlusion (0-7 days postoperatively) was not different between the groups, while there were significantly move late symptomatic vein graft occlusions (7-60 days postoperatively) in Group II (RT) 4.4% than in Group I 1.1%; P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519520 TI - Regression of pre-existing coronary artery disease in a donor heart after cardiac transplantation. AB - This report is about the angiographic follow-up, over 5 years, in a patient with urgent heart transplantation grafted with an atherosclerotic donor heart because of severe congestive heart failure due to dilative cardiomyopathy. Sequential quantitative angiography documented a regression of the luminal narrowing of a focal lesion in the right coronary artery with a minimal luminal diameter of 1.38 mm (56% diameter stenosis) in 1988 to 2.78 mm (13%) in 1993. During this catheterization in 1993 intravascular ultrasound imaging illustrated almost no atherosclerotic vessel wall abnormalities at the site of the previous angiographic luminal narrowing as well as in the adjacent segments. These findings might promote the potential acceptance of heart transplant donors with a certain extent of coronary artery disease in the case of urgent organ request, if close follow-up and strict guidance of the patient by the transplanting team is feasible. PMID- 8519521 TI - Potential neurotoxicity of a novel aminoacridine analogue. AB - 1. A class of compounds, 9-aminoacridines, have long been known to be reversible inhibitors of acetylcholinesterase (AChE-EC 3.1.1.7), the most familiar of which is 9-amino-1,2,3,4-tetrahydroacridine (Tacrine). 2. A novel aminoacridine was synthesised: -2-tertiary-butyl-9-amino-1,2,3,4- tetrahydroacridine (2tBuTHA). 3. In vitro comparisons of the acetylcholinesterase inhibitory potential and neurotoxicity compared to Tacrine were performed using a chemically differentiated neuroblastoma cell line (Neuro 2A). 2tBuTHA, but not Tacrine, was cytotoxic to the neural cell following 20 h exposure, despite being the least potent AChE inhibitor (IC80 AChE 12.53 microM +/- 1.14 s.e.m., Neutral Red Uptake IC50 9.53 microM +/- 0.98 s.e.m., MTT Reduction IC80 14.6 microM +/- 1.43 s.e.m.). 4. In vivo studies used a novel application of a five arm radial maze to assess neuropharmacological effects on working memory in control and Scopolamine (1 mg kg-1 i.p.) treated mice. There was an impairment of short term cognitive function with 2tBuTHA (15 mg kg-1 i.p.), but not Tacrine (10 mg kg-1 i.p.) which improved the Scopolamine deficit as expected. 5. This combined in vitro and in vivo data infers a neurotoxic property for the novel compound 2tBuTHA, a close structural analogue of Tacrine. PMID- 8519522 TI - Time-dependent porphyric response in mice subchronically exposed to arsenic. AB - 1. A time-course study was carried out in mice subchronically exposed to As III (as sodium arsenite) or As V (as sodium arsenate), via drinking water, relating the pattern of urinary porphyrin excretion to the renal and hepatic enzyme activities of porphobilinogen deaminase (PBGD), uroporphyrinogen III synthetase (URO III-S), uroporphyrinogen decarboxylase (URO-D) and coproporphyrinogen oxidase (COPRO-O), as well as to the hepatic porphyrin accumulation in the treated animals. 2. A time-dependent, wave-like porphyric response was found in mice exposed to As V, and the increases seen in total urinary porphyrins (at 3 weeks of exposure) corresponded to an increased activity of PBGD and Uro III-S in liver. 3. Significant decreases in renal URO-D and hepatic and renal COPRO-O activities were found in treated mice; these inhibitions were more pronounced in animals exposed to As III. 4. The combination of these enzymic effects may explain the time-dependent porphyric response of mice subchronically exposed to As. Finally, the relative magnitudes of URO-D and COPRO-O inhibitions may determine the pattern of porphyrin concentration observed in urine and tissues. 5. The decrease in renal URO-D activity may help to explain the inversion in the coproporphyrin/uroporphyrin ratio previously reported in humans chronically exposed to As; however, there were differences between the urinary porphyrin profiles found in both species. The possible reasons for the similarities and differences are briefly discussed. PMID- 8519523 TI - Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat. AB - 1. The toxic manifestations of dermally applied hexachlorocyclohexane (50 mg or 100 mg kg-1 body weight day-1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2. The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase (beta Gluc.) associated with specific cell types. 3. Significant quantities of HCH and its isomers accumulated in testes as well as sperm of treated rats. 4. HCH exposure also led to a decrease in serum testosterone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5. These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field. PMID- 8519524 TI - Effects of decoctions prepared from Aconitum carmichaeli, Aconitum kusnezoffii and Tripterygium wilfordii on serum lactate dehydrogenase activity and histology of liver, kidney, heart and gonad in mice. AB - Mature ICR mice were randomly divided into groups and treated with various doses (1 mg, 5 mg or 10 mg herb/25 g body weight) of a decoction of one of three following Chinese medicinal herbs: Aconitum carmichaeli, Aconitum kusnezoffi and Tripterygium wilfordii, once daily for 4 days. Twenty four hours after the last injection the animals were bled and the blood samples were stored at -20 degrees C until assay for liver lactate dehydrogenase (LDH) isozyme activity. The livers, kidneys, hearts and gonads were dissected out, immediately fixed in Bouin's fluid, and subsequently processed for histological examination. It was found that the gonads and hearts of the drug-treated mice were histologically similar to those of control animals. After treatment with the lowest dose of the herbs i.e. 1 mg/25 body weight, the liver and kidney did not undergo observable changes. However, the herbs at the doses of 5 mg and 10 mg/25 g body weight produced damaging effects on the liver and kidney, the effects produced by the higher dose being more dramatic. The tissue damage was accompanied by elevations of liver LDH isozyme activity in the serum. PMID- 8519525 TI - Renal filtration and excretion of aluminium in the rat: dose-response relationships and effects of aluminium speciation. AB - The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove aluminium from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 micrograms (0.93 mumol) to 800 micrograms (29.6 mumol) aluminium, and aluminium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of aluminium, and hence determine aluminium reabsorption. At all doses of administered aluminium, that administered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excretion of aluminium administered as citrate was not significantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate. It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an aluminium citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to prevent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration. PMID- 8519526 TI - Chronic copper intoxication due to ingestion of coins: a report of an unusual case. AB - We report an unusual case of acute copper intoxication in a patient who died after swallowing more than 700 coins mainly of 1p and 2p denomination. At autopsy the liver showed fibrosis and extensive copper deposition was demonstrated in the histological sections. Electron probe microanalysis also confirmed the presence of copper in the hepatic tissue. PMID- 8519527 TI - Polycyclic aromatic hydrocarbons in placenta, maternal blood, umbilical cord blood and milk of Indian women. AB - Human placenta, umbilical cord blood, maternal blood and breast milk samples from mothers were analysed for the presence of selected polycyclic aromatic hydrocarbons (PAHs). Benzo(a) pyrene (B(a)P), dibenzo(a,c)anthracene (DBA) and chrysene (Chy) were detected in all the four types of sample. Levels of dibenzo(a,c)anthracene were higher in the above samples compared with the other two PAHs. Umbilical cord blood and breast milk samples showed relatively high concentrations of all the three PAHs and thus demonstrated that the developing foetus/new born were exposed to these carcinogenic environmental contaminants. The possible implications of PAHs in relation to human health are discussed. PMID- 8519529 TI - Symposium on Structure-Activity Relationships in Toxicology. Marseilles, France, 18-19 April 1994. Abstracts. PMID- 8519528 TI - Evaluation of the generation of genotoxic and cytotoxic metabolites of benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen using human liver microsomes and human lymphocytes. AB - 1. The ability of model stable epoxides and metabolites generated by human liver microsomes from benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen to produce cytotoxicity and genotoxicity in human peripheral lymphocytes has been investigated. 2. The stable epoxides 1,1,1 trichloropropene-2,3-oxide (100 microM) and trans stilbene oxide (100 microM) as well as metabolites generated from aflatoxin B1 (30 microM) and naphthalene (100 microM) by an extracellular metabolising system were toxic to isolated resting mononuclear leucocytes (MNLs), whereas glycidol (100 microM), benzo[a]pyrene (100 microM) and tamoxifen (50 microM) were not. 3. The stable epoxides 1,1,1 trichloropropene-2,3-oxide (100 microM) and trans stilbene oxide (100 microM) but not glycidol (100 microM) were toxic to dividing lymphocytes only after a 72-h exposure. Tamoxifen (30 microM), aflatoxin B1 (30 microM) and their metabolites were also toxic to dividing lymphocytes. Benzo[a]pyrene (100 microM) and naphthalene (100 microM) were not toxic either in the absence or presence of the extracellular metabolising system. 4. Benzo[a]pyrene (100 microM) and aflatoxin B1 (30 microM) were directly genotoxic to lymphocytes, this genotoxicity was significantly enhanced by the presence of the extracellular metabolising system. This indicates that both intracellular and extracellular bioactivation of these two compounds can produce genotoxicity. In contrast, naphthalene and tamoxifen were non-genotoxic. PMID- 8519530 TI - Dangerous liaisons? Identification and characterization of DNA elements implicated in the regulation of CYP4A1 transcription. PMID- 8519531 TI - More on adducts and addicts. Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer. PMID- 8519532 TI - Connexin genes as tumour suppressor genes? PMID- 8519533 TI - A fly in the ointment. Induction of oxidative DNA damage and enhancement of cell proliferation in human lymphocytes in vitro by butylated hydroxyanisole. PMID- 8519534 TI - [Effects of total gastrectomy on the nutritional status]. AB - In this study, we have analyzed a series of 88 patients who underwent total gastrectomy followed by two different reconstructive procedures, Roux-en-Y jejunal interposition (57%) and interposition of a jejunal limb between the oesophagus and the duodenum (38%) (Henley procedure). We examined diet, intestinal transit, symptoms of dumping syndrome and body weight curves. Patients with Roux-en-Y reconstruction presented post-prandial sweating more often (48%) than patients with the Henley procedure (21%). Forty percent patients with Roux en-Y reconstruction suffered post-prandial nausea whereas this finding was not associated with patients after the Henley procedure. The reconstructive method has to be chosen considering the age and general condition of the patient, stage of the neoplasia and its curability. We currently favor Roux-en-Y esophagojejunostomy. However, in selected patients the Henley procedure may prove useful in order to prevent reflux and dumping symptoms. PMID- 8519535 TI - [Energy expenditure of patients with Crohn's disease. Course study during hospitalization]. AB - Weight loss and protein energy malnutrition are frequent in Crohn's disease. The increase of resting energy expenditure has been pointed out as the cause of these findings. In this study we report eleven patients with Crohn's disease, six women and five men hospitalized with active Crohn's disease. In three patients the disease involved the small bowel, in five the large bowel and three shared large and small bowel involvement. At the beginning of the hospitalization the activity disease index of Van Hees was 196 +/- 52, range: 132-265. The resting energy expenditure was eleven percent higher than that, of a healthy population (p: n.s). During hospitalization the energy expenditure decreased weekly with statistically significant difference. No relation has been observed between the activity index of Van Hees, and any of the energy parameters studied. Patients with body weight lower 90% of ideal weight, had an increased resting energy expenditure when that was expressed in kcal/kg of weight (p = 0.003). Fever was the sole parameter analyzed with statistically significant relation with consumption of oxygen: with the index of oxygen consumption (p = 0.03) and with the percentage of resting energy expenditure (p = 0.006). In summary, the REE in active Crohn's disease is higher than that of healthy population, although without statistically significance. The REE tends to normalization coinciding with the decreasing of inflammatory activity. Increased energy expenditure has been detected in weight loss patients. PMID- 8519536 TI - [Peritoneal carcinomatosis. Review of CT findings in 107 cases]. AB - CT findings of 107 patients with non lymphomatous malignant peritoneal disease were retrospectively evaluated. The most common malignancies encountered were ovarian neoplasms (46%), followed by gastric (14%) and colonic carcinomas (10%). In 12 cases (11%) the primary site was unknown. Peritoneal and extraperitoneal findings were evaluated. Signs most frequently observed were: peritoneal implants (82%), ascites (70%), mesenteric implants (65%) and omental involvement (52%). Appreciation of the spectrum of CT findings in peritoneal carcinomatosis is essential for an accurate evaluation of scans in patients with abdominopelvic malignancies. PMID- 8519537 TI - [Asymptomatic carriers of HBsAg: is a follow-up necessary?]. AB - We evaluated the clinical and epidemiological data of 142 HBsAg carriers. This prospective trial is part of a program of study and follow-up in HVB patients. The median age was 34.58 years old, males 56.3%. The average follow-up was 32.4 months. Complete clinical history, routine analysis, liver function tests, alfa fetoprotein, serology for HVB, HCV and HDV and abdominal ecography were done in all patients. DNA-HVB was done only in special cases. Patients with less than 6 months of follow-up were excluded. The 118 remaining carriers were classified into two groups, depending on ALT values. Group 1 (normal ALT): included 98 carriers, 3 of them developed an active chronic hepatitis that was treated with interferon. A small CHC was diagnosed in another patient and it was resected. Group 2 (elevated ALT): included 20 carriers, only 9 of them agreed to biopsy and we found severe hepatic lesions in 4 of them. No group presented coinfection with HCV or HDV. No patient died. We conclude that the study and follow-up of asymptomatic HBsAg carriers permits an early diagnosis and treatment of the complications of this pathology (chronic hepatitis, CHC, etc); in our study, three patients developed chronic hepatitis, successfully treated with interferon, and one small size CHC was diagnosed in another patient. The study of relatives permits also detect subclinic liver disease and facilitates vaccination to prevention transmission of this infection. PMID- 8519538 TI - [Characteristics of chronic delta hepatitis in patients wih HIV infection]. AB - BACKGROUND: Hepatitis Delta virus (HDV) induces severe liver disease in HBsAg carriers. In regions such as Spain, drug addicts make-up a large part of the HIV positive population and they are at risk of HDV infection. Natural history of chronic hepatitis D is not well known in HIV-infected patients. METHODS: We reviewed the clinical charts of 37 patients attending our institution from 1989 to 1993, fulfilling the criteria for chronic hepatitis D. We compared all clinical, epidemiological, serological and histological findings between both HIV positive and HIV-negative patients. RESULTS: All the following parameters showed significant statistical differences between the both groups: mean ALT levels (175 vs 79 respectively, p < 0.05), previous episodes of hepatic decompensation (37% vs 10%, p < 0.01), the circulating Delta antigen (26% vs 10%, p < 0.05), the presence of HBeAg in serum (41% vs 0%, p < 0.01) and the HCV coinfection (85% vs 20%, p < 0.01). Histological findings were not significantly different comparing both groups, as chronic active hepatitis with cirrhosis was the most common diagnosis. CONCLUSION: Chronic hepatitis D may present a more severe course in HIV-infected patients. The higher replication of HDV and the presence of HCV coinfection could explain this worst outcome. PMID- 8519539 TI - [Sedation in endoscopy]. PMID- 8519540 TI - [Primary gastric lymphoma in an HIV positive patient]. AB - We report the case of a young male patient, VIH (+), who was admitted in our hospital with severe epigastric pain. Endoscopical and histological diagnosis was primary gastric non-Hodgkin lymphoma without Helicobacter pylori. The patient was treated with chemotherapy by CHOP scheme (6 cycles), with high clinical improvement and endoscopical and histological regression of the lesion. We comment some features of this peculiar association. PMID- 8519541 TI - [Ticlopidine-induced cholestatic hepatitis. A case report]. AB - A 74-year-old man with cholestatic hepatitis after 3 months of taking ticlopidine is presented herein. Viral serology and autoantibodies were negative. There was no evidence of biliary tree obstruction. After ticlopidine was discontinued, liver tests were normal in 3 months. We review the other cases published in the literature. PMID- 8519542 TI - [Ischemic hepatitis following liver biopsy in a patient with transplanted liver]. AB - We report a case of ischemic hepatitis following a percutaneous liver biopsy in a 51 year old female patient, who had had an orthotopic liver transplant 6 months before. The angiographic study demonstrated a marked stenosis in the hepatic artery at the anastomosis site and a small arterioportal fistula. We suggest that the percutaneous liver biopsy was partially responsible for the ischemic hepatitis, due to the development of a small arterioportal fistula in a previously damaged vascular area with hepatic artery stenosis. PMID- 8519543 TI - [Hepato-cholangiocarcinoma with diffuse metastases and hypercalcemia]. AB - The combined hepatocellular-cholangiocarcinoma (C-HCC) is a very uncommon neoplasm, its diagnosis is difficult and its course is usually very rapid. We report the case of a patient with CHCC type II or transitional tumor, which shows two cellular types in certain zones. Our patient had tumoral hypercalcemia as well, which was very difficult to control. There was a metastatic spread with cholangiolar features almost from the beginning, that made impossible any sort of therapy. It seems that dissemination followed lymphatic pathways. PMID- 8519544 TI - [Epithelioid hemangioendothelioma: a rare hepatic tumor]. AB - We present a case of epithelioid hemangioendothelioma of the liver (EHL). The imaging techniques did not permit the diagnosis. A liver biopsy was done under laparoscopy. One year later, the patient remains without symptoms in spite of the presence of lung metastases and the therapeutic abstention. The most outstanding aspects of this rare hepatic tumor are discussed. PMID- 8519546 TI - [Enterovesical fistula in Crohn's disease. Importance of CT and therapeutic management]. PMID- 8519545 TI - [Acute cholecystitis caused by cystic polyp]. AB - We present the case of a 72 years-old woman with acute cholecystitis, secondary to the obstruction of the cystic duct by a 5 mm adenomatous polyp. Diagnosis of gallbladder polyps is mainly based on ultrasonographic exploration. The recovery was uneventful. PMID- 8519547 TI - [Epilepsia partialis continua: an unusual complication of liver insufficiency]. PMID- 8519548 TI - [Acute pancreatitis and erythromycin]. PMID- 8519549 TI - [Intestinal obstruction by intestinal cystic lymphangioma]. PMID- 8519550 TI - [Laparoscopic repair of spigelian hernia]. PMID- 8519551 TI - Interview with Fiona Stuart-Wilson. Interview by Teresa Jane Waddington. PMID- 8519552 TI - NHS dentistry--the road to a better future. PMID- 8519553 TI - NHS dentistry--the road to a better future. PMID- 8519554 TI - NHS dentistry--the road to a better future. PMID- 8519555 TI - The GDC in a muddle. PMID- 8519556 TI - Denture cleaning. PMID- 8519557 TI - Growth of new dental practices. PMID- 8519558 TI - Reducing anxiety. PMID- 8519559 TI - Self directed learning in the undergraduate dental curriculum. AB - An evaluation of self-directed learning (SDL) in the clinical curriculum was undertaken at the Dental School of the London Hospital Medical College in 1995. Surveys of staff and students produced evidence of variation in viewpoint within and between groups concerning what the term means and how valuable a tool for learning it is. Lack of clarity of definition and purpose of SDL in General Dental Council guidance is highlighted and linked to the desirability of giving further consideration to SDL. PMID- 8519560 TI - Are anterior occlusal radiographs indicated to supplement panoramic radiography during an orthodontic assessment? AB - Five hundred pairs of dental panoramic tomographs (DPT) and maxillary anterior occlusal radiographs (AO) from patients referred to the orthodontic department of a dental teaching hospital were examined to assess the diagnostic yield from a panoramic radiograph of the premaxillary region alone and then assess the additional yield when this view was supplemented by a maxillary anterior occlusal radiograph. Of the 500 DPTs assessed, 208 (42%) lacked clarity of the premaxillary region when the labial segments were used to locate the patient in the DPT machine. An association was found between patients who had abnormal incisor relationships and poor clarity in the premaxillary region of the DPT. Overall 165 (33%) of the supplementary AO views were used to support or refute findings identified on the DPT. It was concluded that in patients referred for an orthodontic assessment, supplementary radiography of the premaxilla may be justified in the following situations: 1. unsatisfactory image quality which may frequently be the case where there are abnormal incisor relationships, 2. localisation of tooth position by vertical parallax and 3. where a reasonable expectation that pathology exists on clinical grounds. PMID- 8519561 TI - The use of artificial intelligence to identify people at risk of oral cancer and precancer. AB - Artificial intelligence is being used increasingly as an aid to diagnosis in medicine. The purpose of this study was to evaluate the ability of a neural network to predict the likelihood of an individual having a malignant or potentially malignant oral lesion based on knowledge of their risk habits. Performance of the network was compared with a group of dental screeners in a screening programme involving 2027 adults. The screening performance was measured in terms of sensitivity, specificity and likelihood ratios. All subjects were examined independently by a dental screener and a specialist, who provided a definitive diagnosis, or 'gold standard', for each individual. All subjects also completed an interview questionnaire regarding personal details, dental attendance and smoking and drinking habits. The neural network was trained on 1662 of the screened population using ten input variables derived from the questionnaire along with the outcome of the specialist's diagnosis. Following training, the network was asked to classify the remaining unseen proportion (365 individuals) of the screened population as positive or negative for the presence of cancer or precancer. The overall sensitivity and specificity of the dentists were 0.74 [95% confidence interval (CI), 0.62-0.86] and 0.99 (95% CI, 0.985 0.994) respectively compared with 0.80 (99% CI, 0.55-1.00) and 0.77 (95% CI, 0.73 0.81) for the neural network. In view of the potential costs involved in implementing a screening programme, this neural network may be of value for the identification of individuals with a high risk of oral cancer or precancer for further clinical examination or health education. PMID- 8519562 TI - Evaluation of guided tissue regeneration in the treatment of paired periodontal defects. AB - The aim of the present study was to compare guided tissue regeneration with conventional surgery in matched periodontal defects within the same subject. Twenty pairs of sites in nine subjects were treated. Surgery was performed at both test and control sites on the same visit. Random allocation was not performed until all preparation and root instrumentation had been completed. Test defects were covered with e-PTFE membranes (Gore-Tex) and secured with sutures. Membranes were removed after 5-6 weeks with a second surgical procedure, whereas the control sites were not re-operated. At 12 months probing depth reductions were significantly greater at the Gore-Tex treated sites (P<0.05) but no difference in probing attachment level gains were found when compared with conventional flap surgery. PMID- 8519564 TI - Modern imaging of head and neck tumors. PMID- 8519563 TI - Radical changes for the financing of dental treatment in The Netherlands. AB - The first of January 1995 brought several profound changes in Dutch dental care. As of that date, a considerable number of dental treatments are no longer covered by basic health insurance. This decision, made by the Minister of Public Health, Welfare and Sports, Dr E Borst, is one with major consequences. PMID- 8519566 TI - Classification of spontaneous dural arteriovenous fistulas. PMID- 8519565 TI - Advanced imaging of head and neck tumors. PMID- 8519567 TI - Classification of spontaneous dural arteriovenous fistulas with regard to their pathogenesis. AB - PURPOSE: A classification of dural arteriovenous fistulas (DAVFs) according to their pathogenesis has not been established. The purpose of this study was to examine the hypothesis that the different angiomorphologies of DAVFs depend on the location of the venous recipient, and that a territorial classification of spontaneous DAVFs can be created based on their acquired development. MATERIAL AND METHODS: The clinical and radiographic findings of 96 patients with DAVFs were reviewed, especially with regard to their venous characteristics. RESULTS: DAVFs were subdivided into 5 groups: Type 1--DAVFs of the dural sinuses (n = 39); Type 2--DAVFs of the cavernous sinus (n = 29); Type 3--DAVFs of Galen's system (n = 10); Type 4--DAVFs of the venous plexus at the base of the skull (n = 9); Type 5--DAVFs of the parasinusal cortical veins (n = 9). The documentation of a causal sinus thrombosis depends on the location of the DAVF: in 72% of the cases with type 1 DAVFs there was a thrombosis at the time of the investigation, but no thrombosis could be proved in cases with type 4 DAVFs. CONCLUSION: The morphological development of DAVFs seems to depend on the flow volume of the venous recipient. A pronounced development of pathological AV shunts takes place at the level of the large basal dural sinuses. A delayed development of pathological AV shunts with a low shunt volume occurs in a venous recipient with a low AV pressure gradient. PMID- 8519568 TI - CT features of olivopontocerebellar atrophy in children. AB - Between 1990 and 1992, 14 children were seen in whom a clinical diagnosis of olivopontocerebellar atrophy (OPCA) had been made. The majority of patients presented with cerebellar ataxia and hypotonia. Five children had a family history of a similar illness in first-degree relatives. All cases had undergone clinical and neurologic examinations, routine laboratory tests and cranial CT. CT features were graded to quantitate the degree of atrophy in each cerebellar hemisphere, vermis and brain stem. All patients had varying degrees of atrophic changes of cerebellum, brain stem and cerebrum. These CT features appear to be distinctive enough to enable the diagnosis of OPCA to be made. PMID- 8519569 TI - Skull metastasis from hepatocellular carcinoma. CT, MR and angiographic findings. AB - CT, MR and angiographic findings of 6 patients with 9 skull metastases from hepatocellular carcinoma (HCC) were reviewed. In 3 of 6 patients, local pain or neurologic deficit was the initial main manifestation of the disease, although all had been treated for chronic liver disease. In the remaining 3 patients, skull metastases were detected following treatment of HCC. The metastatic lesions appeared as expansile osteolytic masses on CT and as hypervascular masses on angiography. All lesions were demonstrated on MR imaging. Compared with the brain parenchyma, the lesions were iso- or hypointense on T1-weighted and T2-weighted MR images. The lesions were moderately to markedly enhanced by Gd-DTPA. Flow voids were shown in the tumors in 5 lesions. HCC should be included in the differential diagnosis of an osteolytic hypervascular lesion of the skull, especially in Oriental patients. The relatively hypointense tumor on T2-weighted MR images associated with flow void, different from primary skull tumors or directly invasive tumors, may support the diagnosis of HCC metastasis. PMID- 8519570 TI - MR imaging of 495 consecutive cases with sensorineural hearing loss. AB - PURPOSE: To examine patients with sensorineural hearing loss (SNHL) with MR. MATERIAL AND METHODS: 495 consecutive patients with SNHL and 120 age-matched healthy controls were examined. Spin-echo (SE) and fast spin-echo (FSE) images were used with 1.5 T equipment. RESULTS: An intracranial abnormality was found in 211 (42.6%) of the patients with 95 (19.2%) along the acoustic pathway. Eleven of the 95 patients had sensory hearing loss while 84 had neural hearing loss with the retrocochlear auditory pathway affected by lesions. In 62 of the 84 patients, the internal acoustic canal and cerebellopontine angle were involved. Twenty-two patients had intra-axial lesions. The controls had no pathologic changes along the auditory pathway. CONCLUSION: MR imaging in a patient with SNHL must cover the entire acoustic pathway from the cochlea to the superior temporal gyrus, and all the components of the auditory pathway should be scrutinized. The FSE technique can be used to detect the lesions causing SNHL. FSE-sequences can replace SE-sequences. PMID- 8519571 TI - Adrenoleukodystrophy. A case report. AB - PURPOSE: Adrenoleukodystrophy is a hereditary, usually X-linked recessive disorder, characterized by progressive demyelination of cerebral white matter and adrenal insufficiency. MATERIAL AND METHODS AND RESULTS: We report the case of a 14-year-old boy, presenting the typical changes in CT and MR with almost symmetrical changes in the white matter only, with no mass effect and a rim of enhancement. Adrenoleukodystrophy may resemble tumour but shows no mass effect. DISCUSSION AND CONCLUSION: We discuss the differential diagnoses and underline the importance of the characteristic appearance of this disease. Adrenoleukodystrophy is diagnosed by serum analysis. PMID- 8519572 TI - CT-diskography, diskomanometry and MR imaging as predictors of the outcome of lumbar percutaneous automated nucleotomy. AB - PURPOSE: This prospective study was performed to assess whether CT-diskography (CT-D), diskomanometry (DMM) including recording of the pain response, or the MR signal intensity of the disks are reliable predictors of the outcome of nucleotomy. MATERIAL AND METHODS: Ninety-one patients, 44 females and 47 males aged 18-68 years (mean 37.4) treated at 99 disk levels were included. All had plain CT, MR imaging, CT-D and DMM performed prior to automated percutaneous nucleotomy with the Nucleotomy R system. RESULTS: Sixty-nine (76%) of the patients responded well to treatment within 3 months. Due to recurrences, the success rate at 1 year was reduced to 65%. Except for better results following nucleotomy in patients with similar and identical pain as the presenting complaint provoked at diskography, no association was demonstrated between diskographic parameters, or loss of signal on MR, and the outcome. Better results were also seen in patients with a short history of disk disease, but not in patients with predominantly sciatica and focal hernias compared to those with predominantly low-back pain and diffuse posterior bulges. CONCLUSION: The results do not justify routine use of diskography prior to nucleotomy in patients with pathologic disks demonstrated by noninvasive methods and localizing sciatic pain. PMID- 8519573 TI - Diagnosis by ultrasound of dislocated ulnar collateral ligament of the thumb. AB - The ability of ultrasound to assess a displaced ulnar collateral ligament of the 1st metacarpo-phalangeal (MCP) joint was evaluated. If the ligament is ruptured and displaced proximal to the adductor aponeurosis, a surgical repair should be undertaken to restore stability. Ultrasound accurately diagnosed these lesions in 32/39 operated patients. In 4 cases the ultrasound examination suggested a more severe lesion than was found at operation. In 3 cases a lesser injury was suspected than later proved to be present. PMID- 8519574 TI - CT-assessment of dependent lung densities in man during general anaesthesia. AB - PURPOSE: We aimed to describe the frequency of atelectasis occurring during anaesthesia, to describe the size and pattern of the atelectasis, and to standardise the method of identifying the atelectasis and calculate its area. MATERIAL AND METHODS: Patients (n = 109) scheduled for elective abdominal surgery were examined with CT of the thorax during anaesthesia. RESULTS: In 95 patients (87%) dependent pulmonary densities were seen, interpreted as atelectasis. Two different types of atelectasis were found-homogeneous (78%) and non-homogeneous (9%). Attenuation values in histograms of the lung and atelectasis were studied using 2 methods of calculating the atelectatic area. CONCLUSION: On the basis of the present findings, we defined atelectasis as pulmonary dependent densities with attenuation values of -100 to +100 HU. PMID- 8519575 TI - MR imaging of gadolinium-DTPA-BMA-enhanced reperfused and nonreperfused porcine myocardial infarction. AB - To investigate whether Gd-DTPA-BMA-enhanced MR imaging permits differentiation between reperfused and nonreperfused myocardial infarction, myocardial infarction was induced in 12 domestic pigs. In 6 pigs, Gd-DTPA-BMA, 0.3 mmol/kg b.w. was administered i.v. 60 min after the occlusion. In 6 other pigs, the infarctions were reperfused 80 min after the occlusion, followed by injection of Gd-DTPA-BMA after 20 min of reperfusion. Radiolabeled microspheres were used to confirm zero flow during the occlusion period and reperfusion in the infarcted myocardium. All pigs were killed 20 min after injection of contrast medium, and the hearts were excised and imaged with MR. The Gd concentration was measured in infarcted and nonischemic myocardium by ICP-AES. In the reperfused hearts, the infarctions were strongly highlighted, corresponding to a 5-fold higher Gd concentration in infarcted vis-a-vis nonischemic myocardium. In the hearts subjected to occlusion without reperfusion, there was only a rim of enhancement in the peripheral part of the infarctions. PMID- 8519576 TI - AMBER chest radiography and patient dose measurements. AB - PURPOSE: Improved chest imaging has been reported with the usage of AMBER (advanced multiple-beam equalization radiography) equipment but with a higher patient radiation dose compared with conventional chest radiography. Most studies, however, describe dose measurements from phantoms. This study presents a comparison of radiation dose measurements in 57 patients for p.a. projections from an AMBER unit with and without an extra Cu filtration and from a formerly used conventional Siemens chest stand. MATERIAL AND METHODS: Dose measurements were performed with thermoluminescence dosimetry. Entrance surface doses were recorded from 5 dosimeters, placed on the patient's back. Four were placed over the upper and lower lung fields, respectively, and 1 over the mediastinal area. The dose values were then compared with the values obtained from the conventional chest stand and from the measurements with the extra filtration on the AMBER system. RESULTS: The mean entrance dose for the mediastinal area was 0.25 mSv (range 0.15-0.49). With the extra Cu filtration it was 0.16 mSv (0.07-0.29). For the lung fields the values were 0.19 mSv (0.07-0.44) and 0.10 mSv (0.02-0.31), respectively. For the conventional chest stand the entrance dose to the patient was 0.23 mSv. CONCLUSION: AMBER entrance surface doses for the p.a. projection without extra Cu filtration were comparable to the doses obtained with the formerly conventional Siemens chest stand and were well within European recommendations. With extra Cu filtration the AMBER entrance surface doses were reduced by a factor of almost 2. PMID- 8519577 TI - Neural tolerance of the non-ionic dimers iodixanol and iotrolan and the non-ionic monomer iopamidol during myelography in non-anaesthetised rabbits. AB - PURPOSE: The neural tolerance of the recently introduced dimer iodixanol (320 g I/l) was compared with that of the dimer iotrolan (300 g I/l) and of the monomer iopamidol (300 g I/l), both used in clinical myelography. MATERIAL AND METHODS: Non-anaesthetised rabbits were injected into the cisterna magna with Ringer's solution (control) or contrast media (CM) at doses of 1.0 or 0.5 ml/kg b.w. The behaviour of the animals (10 in each of 7 groups) was evaluated for signs of excitation and depression during the first 3 hours after injection. RESULTS: At the dose level of 1.0 ml/kg b.w., iodixanol produced no seizures but did cause focal twitching in 4/10 rabbits. Iopamidol produced grand mal seizures in 2/10 and hyperexcitability in 4/10 rabbits. Iotrolan produced generalised grand mal seizures in 8/10 rabbits, an incidence of excitation significantly greater than that of iodixanol (p < 0.01) and iopamidol (p < 0.05). The excitative effects of iodixanol were not significantly different from those of iopamidol and Ringer's solution. All 3 CM produced similar depressive effects on rabbit behaviour. Ringer's solution caused no depressive effects (p < 0.01). A clear dose response was produced with all 3 CM after treatment with a lower dose of 0.5 ml/kg b.w. CONCLUSION: The results indicate that the neural tolerance in the rabbit of iodixanol is higher than that of iotrolan, and is at least equal to that of iopamidol. PMID- 8519578 TI - Cine phase contrast angiography of normal and diseased peripheral arteries. Preliminary results. AB - Cine phase contrast angiography (PCA) is a modified MR phase contrast sequence that acquires up to 22 coronal phase images per mean cardiac cycle. The ability of the sequence to visualise local haemodynamics was investigated in 7 normal volunteers and 9 patients with flow disturbances of the peripheral arteries using a 1.5 T imager. Functional flow information provided by coronal cine PCA was correlated with quantitative data obtained by MR flow measurements and vessel morphology confirmed by conventional angiograms. Due to the yet suboptimal image quality, an aortic dissection and 1 of 4 aneurysms could not be depicted morphologically. The temporal pattern of arterial perfusion in cine PCA corresponded with flow velocity versus time data provided by quantitative MR flow measurements. Accuracy and time resolution of cine PCA was thus sufficient to provide functional information on the severity of occlusive vascular disease. PMID- 8519579 TI - MR imaging of adult colo-rectal intussusception. A case report. AB - MR imaging of an intussuscepted sigmoid cancer misinterpreted as a rectal carcinoma is described. High-resolution technique with pelvic-phased array coils and fast spin-echo was used. The diagnosis is discussed in relation to the MR findings. PMID- 8519580 TI - CT and MR imaging of adrenal hemangioma. A case report. AB - PURPOSE: Cavernous hemangiomas of the adrenal gland are rare, and we here describe CT and MR features of an additional case including delayed contrast CT. RESULTS: On CT, the tumor appeared as a well-delineated mass. Fatty areas and calcifications were seen. On delayed contrast CT, a progressive enhancement from the periphery to the center of the tumor was noticed, similar to the contrast enhancement of liver hemangiomas. In T1-weighted MR images, a hypointense tumor with a central stellate area of hypointensity was found. The tumor had a predominantly peripheral contrast enhancement. CONCLUSION: CT and MR findings of adrenal hemangiomas are in some cases similar to those of liver hemangiomas. A tumor resection must be considered if the tumor changes in appearance or size. PMID- 8519581 TI - Use of an enhanced gradient system for diffusion MR imaging with motion-artifact reduction. AB - PURPOSE: A spin-echo diffusion-sensitized pulse sequence using high gradients (23 mT/m) is introduced. MATERIAL AND METHODS: In order to minimize motion artefacts, velocity-compensating gradients, ECG-triggering and post-processing with phase correction and raw data averaging using navigator echoes was performed. The in vitro ratio of diffusion coefficients for water and acetone was determined and the water self-diffusion coefficient at different temperatures was evaluated. The pulse sequence was tested in 7 healthy volunteers and in 2 tumour patients with astrocytomas of grades I-II and III-IV. Both single-slice and multi-slice techniques were used. RESULTS: The incorporation of phase correction clearly improved the quality of both diffusion-encoded images and the calculated diffusion maps. Mean values of the diffusion coefficients in vivo were for CSF 2.66 x 10(-9) m2/s and for white and grey matter 0.69 x 10(-9) m2/s and 0.87 x 10(-9) m2/s, respectively. CONCLUSION: Velocity-compensating gradients in combination with a high gradient strength were shown to be useful for in vivo diffusion MR imaging. PMID- 8519582 TI - Ultrasonographic in vitro examination of nonpalpable breast masses. A new method. AB - Specimen radiology is necessary for ensuring successful surgical excision of nonpalpable, clinically occult breast masses discovered by mammography. However, occasionally nonpalpable lesions are only detected by sonography. A simple method of ultrasonographic in vitro identification of nonpalpable lesions invisible on specimen radiographs is presented. PMID- 8519583 TI - Digital optical card. A promising technology for documentation and communication of images. AB - PURPOSE: To assess a patient-oriented digital optical card (OC) for documentation and communication of images using the analysis of breast microcalcifications to illustrate its resolution power. METHODS: Fifty film mammograms with histologically proved clustered microcalcifications were digitized using a 5 lp/mm CCD-scanner. A region of interest containing the cluster was selected for documentation on an OC as an overview OC-image and as a magnified OC-image (5 lp/mm). The shape (spherical/nonspherical) as well as the total number of microcalcifications were quantitatively analyzed by 2 radiologists. RESULTS: The detection rate for total number of overall and spherical microcalcifications using digital media was significantly reduced (p < 0.01) compared to analog mammography. There were no significant differences in the detection rate of nonspherical microcalcifications between film mammograms (100%) and magnified section OC-images (92.7%). The overview OC-image revealed 72% of those calcifications (p < 0.01). CONCLUSION: According to our results, this technology is not appropriate for diagnosis of breast microcalcifications, but may be a promising communication digital medium for transmitting an image/report unit to referring physicians. PMID- 8519584 TI - [Surgical treatment of closed articular fractures of the proximal interphalangeal joints (20 cases)]. AB - 20 cases of intra-articular fractures of proximal interphalangeal joints were reviewed with a mean follow-up of 3 years 9 months, and a minimum follow-up of 1 year, corresponding to 10 fractures of the head of P1 (7 condylar fractures, 2 supra-intercondylar fractures and 1 diaphyseal fracture with an articular crevice) and 10 fractures of the basis of P2 corresponding to distraction impaction fractures in 8 cases. The fractures were treated by open reduction and osteosynthesis by screws, mini-screws, or pins, completed by an arthrodesis pin in 3 cases. All fractures were closed, isolated, and too unstable to be treated orthopaedically. Global results were: 14 excellent and good results, 4 moderate results and 2 poor results according to Steel's criteria. No serious early complications were observed. The difficulty of treatment and the duration of rehabilitation are greater in fractures of the base of P2 than for fractures of the head of P1. No statistically significant factor was identified due to the small size of this series, but, the factors of poor prognosis essentially consist of late mobilization and reoperations for failure of percutaneous pinning of a fracture of the basis of P2. PMID- 8519585 TI - [Articular necroses of the proximal interphalangeal joint. Treatment by resection distraction using a multicentric MS3 fixator]. AB - PIP joint necrosis occurs in multioperated patients with a history of a dorsal and palmar approach to their joint. Seven cases are reported. The surgical treatment consisted of articular resection followed by external distraction using the MS3 device. Four of the patients regained a painless range of movement (30 to 50 degrees): two of these patients had a clinodactyly of 20 degrees. The final range of movement was better when the extensor apparatus was not injured. Three patients were reoperated: a fusion was performed which healed, more rapidly than normal. PMID- 8519586 TI - [A new surgical technique for carpal instability with scapho-lunar dislocation. (Eleven cases)]. AB - A new operation for correcting carpal instability with scapholunate dissociation is presented. Rupture of the volar scaphoid-trapezium-trapezoid ligament (i.e. the fibrous sheath of the F.C.R.) is recognized to play a prominent role in the etiology of this instability. The scar formed in between the scaphoid and lunate bones is removed as well as that formed between scaphoid, trapezium and trapezoid. A slip of F.C.R. is passed throughout a tunnel pierced in the distal pole of the scaphoid. The slip is then sutured to the dorsolunar ridge of the distal radius with correction of both the dissociation and the scaphoid flexion. The operation is easy and quick. Eleven cases are presented with satisfactory results. PMID- 8519587 TI - [Results 37 years after insertion of an acrylic implant for scaphoid pseudoarthrosis]. AB - Prosthetic treatment by means of a scaphoid implant was described by Swanson in 1970. The authors report the long-term results of pseudoarthrosis of the scaphoid treated by an acrylic implant at the Rizzoli Orthopaedic Institute in Bologna in 1956. Only one other similar case of long-term treatment by an artificial Vitallium (r) prosthesis was found in the literature. PMID- 8519588 TI - [Upper limb lengthening. 47 clinical cases]. AB - Between 1989 and 1993, the authors treated 39 patients by progressive bone lengthening in a total of 47 hands (17 post-traumatic and 30 congenital deformities). The Hoffman distractor was used in 34 cases and the Orthofix device was used in 13 cases. The percentage of lengthening obtained, compared to the initial bone length, was 87% for the hand skeleton and 47% for the forearm bones in congenital malformations while only 51% was obtained in post traumatic cases due to their older age and frequently associated skin problems. In 4 (8.5%) of these post-traumatic cases, the skin conditions had to be improved surgically. The average duration of treatment was 6.7 months, with a "healing" index (months/centimeters of lengthening obtained of 1.7. The time necessary to achieve complete bone healing was as long as the lengthening period. The complication rate was 34% (severe pain 8.5% delayed bone healing 8.5%, pin infections 6.3%, bone grafts 4.2%, tendon complications 2.1%), however none of these problems required pin removal. A complete failure was observed in two cases, followed by a second successful operation. PMID- 8519589 TI - [Rupture of the flexor tendons after partial arthrodesis of carpus in the rheumatoid wrist]. AB - The author report two ruptures of flexor digitorum tendons in a series of thirteen partial wrist arthrodeses in rheumatoid arthritis. These ruptures occurred as a result of attrition at the radial epiphysis after reduction of anterior subluxation of the carpus. PMID- 8519590 TI - [Metacarpal aneurysmal cysts. Report of two cases and review of the literature]. AB - The authors present two cases of aneurysmal cyst, one primary and one secondary. The first case was treated surgically by resection and bone graft. The second case, associated with a giant cell tumors, was initially treated surgically by resection and bone graft, but, because of a rapid recurrence of the giant cell tumor, the middle finger had to be amputated. The clinical, radiological and histopathological features of aneurysmal cyst are recalled. The various therapeutic modalities recalled and their value in this particular site are discussed. PMID- 8519591 TI - [Finger fibrosarcoma. A case report]. AB - The hand is a rare site of fibrosarcoma. We report one case in a fifty two year old female patient, presenting with a two-year history of an ulcerated tumor of the palmar aspect of the right index finger. The X Ray showed severe erosion of the 2nd phalanx. Because of the large volume of the tumor, a proximal amputation of the 2nd finger was performed. Histological examination concluded on a fibrosarcoma which was completely resected. No signs of recurrence or distant metastasis were seen after 8 months. The frequency of fibrosarcoma in the hand is 2.7 to 5.3%. These tumors are rarely located in the soft tissues of the hand. The treatment is essentially surgical based on a carcinological resection, which represents the only way to avoid recurrence, which is evaluated to be 12% after amputation. PMID- 8519592 TI - The use of split-thickness hypothenar grafts for coverage of fingertips and other defects of the hand. AB - Over a four year period, hypothenar split-thickness skin grafts were used to resurface a variety of fingertip and other hand defects in 27 patients. All patients achieved uncomplicated primary wound healing with minimal donor site morbidity. At one year follow-up, there was no evidence of late wound breakdown or fissuring of the wounds treated with hypothenar skin grafts. PMID- 8519593 TI - Molecular study and regulation of D-myo-inositol 1,4,5-trisphosphate 3-kinase. AB - D-myo-Inositol 1,4,5-trisphosphate (InsP3) is a critical second messenger involved in signal transduction, i.e., calcium homeostasis. InsP3-kinase directly regulates the levels of InsP3 and D-myo-inositol 1,3,4,5-tetrakisphosphate (InsP4). InsP3 3-kinase is a calmodulin (CaM)-dependent enzyme and is also a target for phosphorylation by protein kinase C (PKC). Molecular cloning of cDNA's encoding proteins presenting InsP3 3-kinase activity establish the existence of distinct isoenzymes (at least three: A, B and C). These isoforms are differentially expressed and regulated by calcium/CaM. Site-directed mutagenesis and chemical modification of InsP3 3-kinase A led to the identification of three charged residues involved in ATP/Mg2+ binding among the catalytic domain and a hydrophobic residue taking part of the CaM binding site. PMID- 8519594 TI - Do pancreatic islet cells from neonatal rats have surface receptors or sensors for divalent cations? AB - The effects of extracellular divalent cations on the intracellular Ca2+ concentration ([Ca2+]i) in neonatal rat islet cells were investigated to determine whether these cells, like several others, have signal-generating surface cation sensors. Raising the external Ca2+ concentration by 1 mM increments triggered either sustained increases in [Ca2+]i or large sharp [Ca2+]i spikes followed by return to a suprabasal level. The external Ca(2+)-triggered [Ca2+]i responses were abolished by treating the cells with the inhibitor of inositol phospholipid hydrolysis, neomycin (1.5 mM), but not by another phospholipase C inhibitor, U-73,122 (2.5 microM), or the voltage-sensitive Ca2+ channel blockers nifedipine (20 microM) and methoxyverapamil (D600; 50 microM). [Ca2+]i responses were also triggered by barium (Ba2+; 1 mM) and cobalt (Co2+; 1 mM). The Ba2+ responses were also inhibited by neomycin and unaffected by nifedipine or D600 and the Co2+ response required external Ca2+. Therefore, neonatal rat pancreatic islet cells may display divalent cation receptors/sensors on their surfaces. Activation of these putative receptors, which are coupled to neomycin-sensitive, voltage-independent, dihydropyridine-insensitive channels, by Ca2+, Ba2+ or Co2+ would trigger [Ca2+]i responses by opening these channels to admit external Ca2+ into the cell. The physiological function(s) of such cell surface divalent cation receptors/sensors and the [Ca2+]i surges they generate in pancreatic islet cells is not known. PMID- 8519595 TI - Adenosine receptor activation potentiates phosphoinositide hydrolysis and arachidonic acid release in DDT1-MF2 cells: putative interrelations. AB - Studies were undertaken in an effort to discern possible mechanisms by which the A1 adenosine receptor agonist cyclopentyladenosine (CPA) enhances the norepinephrine-stimulated (NE-stimulated) hydrolysis of phosphoinositides in DDT1 MF2 cells. Measurements of arachidonic acid release revealed similar behaviours to those observed in measurements of phosphoinositide hydrolysis. In the presence of NE, both second messenger responses were potentiated by the addition of CPA, whereas in the absence of NE, CPA had little or no effect on either second messenger. The stimulation and potentiation of both second messenger responses were enhanced in the presence of extracellular calcium, and in each case these effects were persistent over time. For either second messenger system the stimulation by NE and the potentiation by CPA appeared to utilize separate mechanisms as evidenced by the fact that the potentiations by CPA were selectively antagonized by a cAMP analogue or by pertussis toxin, whereas the stimulations by NE were essentially unaffected by these agents. Inhibition of phospholipase A2 (PLA2) also blocked the potentiation of PLC by CPA, without affecting NE-stimulated phosphoinositide hydrolysis. Furthermore, in the presence of CPA, the exogenous administration of PLA2 was found to stimulate phosphoinositide hydrolysis in these cells. These data are consistent with a hypothesis whereby the apparent potentiation of NE-stimulated phosphoinositide hydrolysis by CPA is actually due to the stimulation by CPA of a second pathway of phospholipase C activity which is additive to that of NE. The activation of PLC and PLA2 by NE produces phospholipid products which may play a permissive role in the pathway coupling adenosine A1 receptors to these phospholipases. The formation of lysophosphatidic acid is suggested as one possible mediator of this permissive effect. PMID- 8519596 TI - Identification of PI-PLC beta 1, gamma 1, and delta 1 in rat liver: subcellular distribution and relationship to inositol lipid nuclear signalling. AB - The subcellular distribution of PI-PLC beta 1, gamma 1, and delta 1 has been investigated in rat liver by western blot and immunohistochemical analysis with a panel of isoform-specific antibodies. The data obtained in situ on cryo-sectioned tissue indicate that PI-PLC beta 1 is predominantly nuclear, while gamma 1 is largely cytoplasmic and delta 1 is sharply restricted to the cytoplasm. In fractionation experiments, the Western blot analysis indicated that the recovery of the nuclear isoforms beta 1 and gamma 1 was not affected by the removal of the nuclear membrane, and that the two enzymes persisted in nuclear matrix and lamina, obtained after nuclease digestion and extraction with high salt and detergent. The assay of the phosphodiesterase activity in different cell fractions correlates with the observed relative abundance of the enzymes, and specific inhibition with neutralizing anti-beta 1 and -gamma 1 isoforms confirms that these are the enzymes active at the nuclear level. These results demonstrate that in rat liver cells, as in other cell types, different members of the PI-PLC family show a discrete intracellular distribution, and suggest that PI-PLC beta 1 and gamma 1 play a central role in modulating the nuclear phosphoinositide cycle. PMID- 8519597 TI - Phosphorylation of MARCKS, neuromodulin, and neurogranin by protein kinase C exhibits differential responses to diacylglycerols. AB - Diacylglycerols (DG) derived from brain phosphatidylinositol (PI) and phosphatidylcholine (PC) and synthetic 1,2-dioleoylglycerol (diC18:1) and 1,2 dioctanoylglycerol (diC8) were tested for their efficacy in stimulating PKC catalyzed phosphorylation of three physiological substrates in the brain, namely, MARCKS, neuromodulin (Nm), and neurogranin (Ng). The A0.5 of these DGs for PKC were variable dependent on the protein substrates; the values were lowest with MARCKS and highest with Ng. With Ng as a substrate the A0.5 of these DGs for PKC gamma were PI- and PC-DGs < diC18:1 < diC8. Both PI- and PC-DGs, in spite of their differences in unsaturated fatty acids content, were similarly effective in stimulating PKC. Since the phosphorylation of MARCKS, as compared to those of Nm and Ng, has the lowest A0.5 with the various DGs, it seems that among these three PKC substrates MARCKS is most readily phosphorylated by PKCs following DG formation in vivo. PMID- 8519598 TI - Differential regulation of phospholipase D and phospholipase C by protein kinase C-beta and -delta in liver macrophages. AB - We have studied activation of phospholipase (PL) C and PLD in liver macrophages labelled with [3H]arachidonic acid. Zymosan, phorbol 12-myristate 13-acetate (PMA), A23187 and fluoride but not arachidonic acid or lipopolysaccharide (LPS) induce an activation of PLD ([3H]phosphatidylethanol (PEt) accumulation). An activation of PLC ([3H]diacylglycerol (DAG) accumulation) is measured with zymosan, PMA and fluoride but not with A23187, LPS or arachidonic acid whereas inositol phosphates are formed with zymosan, only. Removal of extracellular calcium reduces the formation of [3H]PEt and [3H]DAG while pretreatment of the cells with dexamethasone reduces [3H]PEt formation, only. PMA- and zymosan induced activation of PLD and PMA-induced activation of PLC both seem to be mediated by protein kinase (PK) C-beta whereas zymosan-induced activation of PLC is negatively controlled by PKC-delta. We could furthermore present evidence that the release of [3H]arachidonic acid in these cells occurs independent of an activation of PLD. PMID- 8519599 TI - High-density lipoprotein and low-density lipoprotein-mediated signal transduction in cultured human skin fibroblasts. AB - The signalling mechanisms whereby high-density lipoproteins (HDL) and low-density lipoproteins (LDL) affect a number of cellular functions in fibroblasts are unclear. This study has analyzed the influence of HDL3 and LDL on the phosphatidylinositol specific phospholipase C pathway in human skin fibroblasts. Exposure of myo-[2-3H]-inositol prelabelled fibroblasts to HDL3 or LDL elicited major increases in IP1 and minor increases in IP2 and IP3 within 30 s. In fura-2 loaded suspended fibroblasts, HDL3 and LDL increased intracellular Ca2+ concentrations ([Ca2+]i) with comparable rapid, transient kinetics. The dose profiles for HDL3- and LDL-induced increases in [Ca2+]i were also comparable, with half-maximally and maximally effective concentrations being approximately 15 micrograms/mL and approximately 50 micrograms/mL, respectively. HDL3- and LDL induced increases in [Ca2+]i were diminished by approximately 60% (vs. control fibroblasts) in thapsigargin-pretreated fibroblasts, indicating that release of Ca2+ from intracellular pools is the major contributor toward lipoprotein-induced increases in [Ca2+]i. Pertussis toxin-pretreatment of cells completely abolished lipoprotein induced Ca(2+)-transient, indicating the involvement of a guanine nucleotide-binding protein in the signalling process. In [3H]-palmitic acid prelabelled fibroblasts, both HDL3 and LDL were observed to stimulate production of DAG. Activation of protein kinase C (PKC) was analysed by determining the cytosol-to-membrane translocation of both enzymatic activity and immunoreactivity of specific PKC isoforms (alpha, delta, epsilon, and zeta). Stimulation with HDL3 and LDL evoked a rapid (within 2.5 min) translocation of PKC activity, with PKC alpha and PKC epsilon being the isoforms translocated. It is concluded that HDL3 and LDL acutely stimulate a phosphoinositide-specific phospholipase C pathway in human skin fibroblasts. However, the specific cell membrane events mediating this signal transduction remain to be further elucidated. PMID- 8519600 TI - Concentration of enzyme-dependent activation of PLC-beta 1 and PLC-beta 2 by G alpha 11 and beta gamma-subunits. AB - Differential regulation of PLC-beta 1 and -beta 2 by the G-protein alpha-subunit, G alpha 11, and by G-protein beta gamma-subunits was studied utilizing recombinant PLC-beta 1 and -beta 2. Rat PLC-beta 1 and human PLC-beta 2 were purified after recombinant baculovirus-mediated expression in Sf9 cells. The catalytic properties of the purified recombinant isoenzymes were directly compared to PLC-beta 1 purified from bovine brain and PLC-beta 2 partially purified from HL60 polymorphonuclear neutrophils. The recombinant isoenzymes were indistinguishable from the native isoenzymes with respect to dependence of reaction velocity on bulk PtdIns(4,5)P2 substrate concentration, pH, and free Ca2+ concentration. Marked AlF(4-)-dependent activation was observed upon reconstitution of rPLC-beta 1 with the G-protein alpha-subunit, G alpha 11. Activation occurred with a concentration dependence on G alpha 11 for activation and elevation in reaction velocity that was similar to that of native PLC-beta 1. In contrast, G alpha 11 promoted only a small elevation in the catalytic rate of recombinant PLC-beta 2, which was also typical of the native isoenzyme. Maximal reaction rates with respect to PLC-beta isoenzyme concentration were achieved and indicated that rPLC-beta 2 required 10-fold greater concentrations of both G alpha 11 and of rPLC-beta 2 for activation than did rPLC-beta 1. rPLC-beta 1 and rPLC-beta 2 were also differentially regulated by beta gamma-subunits. This differential activation was not the result of different concentration dependencies on beta gamma-subunit for activation, but rather, the result of the greater degree to which the catalytic rate of PLC-beta 2 was elevated by beta gamma-subunits when compared to PLC-beta 1. PMID- 8519601 TI - Involvement of protein kinase C and of protein phosphatases 1 and/or 2A in p47 phox phosphorylation in formylmet-Leu-Phe stimulated neutrophils: studies with selective inhibitors RO 31-8220 and calyculin A. AB - Previously employed non-selective protein kinase inhibitors yielded inconclusive results regarding involvement of protein kinase C (PKC) in phosphorylation of 47 kDa protein (p47 phox) in intact neutrophils stimulated with physiologic agonists of superoxide generation. In the present study, phosphorylation of p47 phox in formylMet-Leu-Phe (fMLP) stimulated neutrophils was potently inhibited in the presence of 0.3 microM RO 31-8220, a selective inhibitor of PKC. These results provide experimental evidence in support of the currently considered essential involvement of PKC in p47 phox phosphorylation in response to physiologic stimulation of neutrophil surface receptors. The fMLP-induced phosphorylation of p47 phox was enhanced and prolonged by calyculin A, a specific inhibitor of protein phosphatases of types 1 and 2A, and such enhanced phosphorylation was also effectively inhibited by RO 31-8220. Our results suggest that the extent and duration of p47 phox phosphorylation in intact fMLP-stimulated neutrophils is probably controlled by a balance between the activities of PKC, on the one hand, and of protein phosphatase(s) of type(s) 1 and/or 2A, on the other. Effects of RO 31-8220 and of calyculin A on the fMLP-induced p47 phox phosphorylation were paralleled by similar effects on superoxide release. Calyculin A and RO 31-8220 were also used to study signal transduction by a post-receptor agonist of superoxide generation, a calcium ionophore A23187. The results of the latter study indicated that PKC was activated in A23187-stimulated neutrophils and was essentially involved in superoxide generation and p47 phox phosphorylation. Further, these results suggested that protein phosphatase(s) of type(s) 1 and/or 2A were also activated in A23187-signalling pathway, and limited the extent of superoxide release and p47 phox phosphorylation. PMID- 8519603 TI - Diffusion and perfusion MR imaging of cerebral ischemia. AB - Over the last few years, diffusion and perfusion magnetic resonance (MR) imaging methods have found increasing user for monitoring the effects of cerebral ischemia under clinical and experimental conditions. Blood perfusion can be visualized by studying the patency of the cerebrovascular bed (MR angiography), by recording exchange of diffusible tracers between blood and brain ([2H]water or [19F]trifluoromethane clearance), or by measuring the volume and transit time of the circulating blood (bolus track or spin-tagging imaging). In addition, changes in blood oxygenation level can be visualized by taking advantage of the susceptibility changes of the magnetic field homogeneity (functional or blood oxygenation-level-dependent imaging). Diffusion imaging is based on the modulation of signal intensity by brain water diffusion. Recording a series of diffusion-weighted images allows calculation of the apparent diffusion coefficient (ADC) and the reconstruction of quantitative ADC images. Brain ADC changes are a function of intra-extracellular water homeostasis and therefore are a sensitive marker of ionic equilibrium. Since disturbances of ion and water homeostasis are among the first pathological alterations induced by brain ischemia, diffusion imaging is able to detect the incipient injury within minutes. Conversely, the reversal of these alterations is able to detect the incipient injury within minutes. Conversely, the reversal of these alterations is an early and reliable predictor of postischemic recovery. Applications of perfusion and diffusion imaging are reviewed in relation to the pathophysiology, the pathobiochemistry, and the therapy of evolving brain infarct after focal ischemia and the manifestation and reversal of ischemic injury during and after global ischemia. PMID- 8519602 TI - Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine. AB - Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), a potential inhibitor of adenosine deaminase (ADA), was tested as an inhibitor of the soluble cyclic nucleotide phosphodiesterase (PDE) isoenzymes from pig and human myocardium. Four soluble PDE activities were resolved from human papillary muscle extracts using anion exchange chromatography (DEAE Sepharose CL-6B). These activities were designated PDE I-IV according to the nomenclature of Beavo. PDE I was stimulated by Ca(2+) calmodulin and PDE II by cGMP (1 microM). PDE III was inhibited by cGMP (1 microM) as well as SK&F 94120, and PDE IV by both rolipram and Ro 20-1724. Enzyme kinetics and inhibition constants were similar with the PDE isoenzymes from pig heart. However, porcine myocardium lacked Ca(2+)-calmodulin-stimulated soluble PDE I activity. The present data reveal that EHNA exerted a concentration dependent inhibition of the cGMP-stimulated PDE II (cGs-PDE) (IC50: 0.8 microM (human), 2 microM (pig)) but did not inhibit the other PDE isoenzymes (IC50 > 100 microM). These findings indicate that EHNA is a potent and, as far as cytosolic PDEs are concerned, selective inhibitor of cGMP-stimulated PDEs. The compound may lend itself for the rational design of other isozyme selective PDE II inhibitors and for examining the specific biological functions of cGs-PDEs. EHNA may be used in systems in which inhibition of ADA is of no concern. Conversely, dual inhibition of both ADA and cGs-PDE by EHNA may cause accumulation of two inhibitory metabolites, adenosine and cGMP, which may act in synergy to mediate diverse pharmacological responses, including antiviral, antitumour and antiarrhythmic effects. PMID- 8519604 TI - Clinical stroke syndromes: clinical-anatomical correlations. AB - The vascular territories of the major cerebral arteries supplying the cerebral cortex, subcortical structures, cerebellum, and brainstem in humans are relatively uniform. Because of their anatomical distribution, and the specialized neurologic functions located within these territories, infraction due to arterial occlusion gives rise to distinct clinical syndromes. Thus, the physical findings on neurologic examination permit a reliable topographic diagnosis. With extensive infraction involving all or major portions of a particular vascular territory, the resultant clinical syndromes tend to be severe, reflecting the large area of involvement. More typically, however, infarcts do not involve a vascular territory in its entirety but are limited to the distribution of secondary branches by various mechanisms of arterial occlusion. Depending on their location, these smaller infarcts produce syndromes that may vary in severity and manifestations. Our understanding of the clinical approach of clinicoanatomical correlations in these forms of cerebral infarction has been facilitated by the widespread use of brain CT and MRI scans, that have virtually replaced the classical approach of clinicopathological correlations in autopsy material. In this review we have divided the manifestations of occlusive cerebrovascular disease according to the vascular territories affected. The distinct clinical syndromes which thus arise and their common mechanisms are described. Correlation is made with the typical CT and MRI images. PMID- 8519605 TI - Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. AB - The coupling of brain cell function to the vascular system is the basis for a number of functional neuroimaging methods relevant for human studies. These include methods as diverse as functional magnetic resonance imaging, positron emission tomography, single photon emission tomography, optimal intrinsic signals, as well as near infrared spectroscopy, a method that may have imaging capabilities in the near future. These methods map a specific localized brain activation through a vascular response, such as an increase in cerebral blood flow or a change in blood oxygenation. To understand these direct maps to obtain high resolution maps of localized functional brain activity, a precise knowledge of the specific underlying physiological mechanisms and methodological properties and restrictions is essential. In this article, these fundamental physiological and methodological aspects will be discussed. After reviewing how the techniques cited obtain maps of functional activity, we will discuss our current knowledge of the physiology of coupling with particular reference to the functional imaging techniques. Specifically, we will consider the function, the mediators, and the hemodynamic mechanisms of coupling and point out potential interference by diet, and neurological disease. PMID- 8519606 TI - Systemic lupus erythematosus and Sjogrens syndrome. PMID- 8519607 TI - Pediatric and heritable disorders. PMID- 8519608 TI - Etiology, environmental relationships, epidemiology, and genetics of systemic lupus erythematosus. AB - The etiology of systemic lupus erythematosus (SLE) and the many lupuslike syndromes continues to challenge investigators. Focus is now on the role of heat shock proteins, apoptosis, the possible role of diet factors, and in particular, the role of lipids. The role of various infections as either triggering mechanisms or in contributing to morbidity is receiving close attention. In particular, retroviruses are being carefully studied with all the molecular tools available. This area has real promise and carries with it the possibility of anti infection treatments. Considerably more attention is being paid to the hormonal aspects of SLE and their modulation of the immune system. Environmental associations continue to intrigue investigators and clinicians, and both drugs and other environmental factors provide excellent investigational models. We continue to need good prevalence and incidence studies. Genetically, there is an increasing sophistication in the type of studies, and the ensuing data may well provide real insights into various subsets of SLE. PMID- 8519609 TI - Lymphocytes, cytokines, inflammation, and immune trafficking. AB - Studies that were published over the past year have added new knowledge to our understanding of cellular abnormalities in systemic lupus erythematosus (SLE). Antigen-specific and "pathogenic" T cells can be identified and characterized in SLE. Interleukin-10 has been added to the factors that may promote B cell overactivity and autoantibody production. Protein kinase isozyme I was shown to be deficient in patients with SLE, indicating defects in cell signaling events. Aberrant expression of adhesion molecules on the surface membrane of leukocytes and endothelial cells was shown, with important mechanistic and therapeutic implications. Disruption of the lymphokine network (anti-interleukin-10 antibody) and the function of adhesion-costimulatory molecules (CTLA-4-immunoglobulin) were shown to be therapeutically significant in murine SLE. PMID- 8519610 TI - Autoantibodies in systemic lupus erythematosus. AB - Autoantibodies in systemic lupus erythematosus (SLE) are targeted predominantly to intracellular nucleoprotein particles. Following analysis of the quantitative and qualitative properties of the humoral immune response as well as identification of the major particles recognized as antigens, current studies are addressing the following questions: How is tolerance lost? What accounts for the selection of the antigens? What perpetuates the autoimmune response in SLE? PMID- 8519611 TI - Antiphospholipid antibodies and antiphospholipid syndrome. AB - More than a decade has gone by since the detailed clinical description of antiphospholipid syndrome (APS). Thrombosis, the main complication of the syndrome, can affect vessels of all sizes; the consistent histopathologic lesion is a bland thrombus without inflammation. Animal models are providing important new data on clinical and pathogenic aspects of APS. New data on the biology of the so-called cofactor beta 2-glycoprotein I is now available. Clearly, the mode of presentation of the phospholipid antigen appears significant, and beta 2 glycoprotein I may play an important part. Regarding treatment, there is further confirmation that long-term anticoagulation therapy with maintenance of a high international normalized ratio is needed in patients with antiphospholipid antibody-associated thrombosis to prevent recurrences. PMID- 8519612 TI - Clinical features of systemic lupus erythematosus. AB - Major findings in the understanding of the epidemiology of systemic lupus erythematosus and in the description and understanding of its presentation and course in individual organ systems are reviewed. The role of serologic tests as correlates of disease activity remains controversial. No consensus has been reached on the association of either corticosteroid dose or of antiphospholipid antibodies with avascular necrosis of bone. Multiple rare presentations of cutaneous lupus have been reviewed during the past year. The role of hormones in the activity of lupus and the use of hormonal agents in the treatment of lupus are rapidly expanding and contentious areas of research. Cognitive function deficit continues to be an area of great interest, with studies differing on whether psychiatric disorders or organic lupus (or both) are responsible. Finally, fatigue and the potential role of fibromyalgia as an explanation for "lupus fatigue," are of major interest. PMID- 8519613 TI - Prognosis and treatment of systemic lupus erythematosus. AB - This article summarizes the evidence for improved prognosis in patients with systemic lupus erythematosus (SLE), including reasons for improved survival, as well as the risk for mortality, which remains high for patients with this disease. Causes of death are reviewed, and prognostic factors are examined. Other outcome measures for prognosis in SLE, including specific organ damage, accumulated damage index, health status, and quality of life are considered. The continuing controversy regarding the use of cyclophosphamide is reviewed, together with new therapeutic approaches. PMID- 8519614 TI - Sjogren's syndrome. AB - The literature published over the past year on Sjogren's syndrome is reviewed, including epidemiology, genetic, environmental, and clinical features. The criteria for the classification of Sjogren's syndrome remain controversial, potentially leading to confusion in clinical practice and in research publications. Dryness of the eyes and mouth can result from either interruption of the neurovascular innervation of the glands or from any infiltrative process that affects the ability of the glands to secrete. Recent studies have demonstrated that sicca symptoms also can result from autonomic neuropathy in patients with diabetes, multiple sclerosis, or systemic lupus erythematosus. It is suggested that the term Sjogren's syndrome be used to describe one subset of patients with sicca symptoms who exhibit particular major histocompatibility complex antigens, the presence of T cell lymphoid infiltrates on glandular biopsy, and specific autoantibodies in their sera. Even using these restrictive criteria for classification, no single environmental factor has been shown as necessary or sufficient for pathogenesis. Recent studies on Epstein-Barr virus have indicated a novel deleted virus in some Chinese Sjogren's syndrome patients. Other patients with sicca symptoms and autoimmune features may have infections with HIV or hepatitis C virus. PMID- 8519615 TI - Nonrheumatic conditions in children including infectious diseases and syndromes. AB - Often, a child is referred for evaluation to a pediatric rheumatologist and found to have a nonrheumatologic disorder. Infections constitute an important group of disorders with potential musculoskeletal system involvement. Reactive arthritis subsequent to infection with Yersinia is discussed, as well as reactive arthritis seen in the course of cystic fibrosis. Musculoskeletal manifestations of tuberculosis and brucellosis are reviewed. The continued presence of acute rheumatic fever in the United States has been documented, but the clinical spectrum of the disease appears to be changing over time. A variety of inherited syndromes may involve the musculoskeletal system, either primarily or as a minor manifestation. The bony dysplasias, another group of disorders, result from abnormal collagen structure and affect musculoskeletal development; clinical findings and new genetic information is reviewed. Descriptions of several rare syndromes (eg, hyaline fibromatosis and hypertrophic osteoarthropathy) also are reviewed here. PMID- 8519616 TI - Juvenile rheumatoid arthritis and spondyloarthropathies. AB - Further insight into the etiology and pathogenesis of juvenile rheumatoid arthritis (JRA) is presented in recent immunogenetic studies, particularly the allele associations of the pauciarticular pattern of disease. Evidence suggests that bacterial heat-shock proteins may be significant in the chronic inflammatory response in children with arthritis. Data on the role of complement activation and cytokines and their receptors also are presented. Coagulopathy in JRA may have more than one etiologic factor, including a viral agent, as may the disease itself. In the treatment of growth abnormalities in JRA, the neuroendocrine system, recombinant growth hormone, intravenous iron therapy, and nutritional supplementation are all areas of recent investigation. In outcome studies, ocular involvement and the presence of circulating IgM rheumatoid factor appear to be risk factors for disability. However, disease of less than 2 years' duration and absence of radiographic lesions likely predict good response to methotrexate therapy. PMID- 8519617 TI - Childhood systemic lupus erythematosus, vasculitis, and rheumatic fever and neonatal lupus. AB - Studies on the long-term outcome of patients with systemic lupus erythematosus not only give us survival figures but also uncover flaws in our treatment strategies and reveal both disease-associated and other factors that affect prognosis. Among the latter, compliance with treatment and socioeconomic factors are noteworthy. The pathogenesis of neonatal lupus is under active investigation, and new approaches are being developed. This review also draws attention to a number of vasculitis syndromes that are common in adults but very rarely reported in children. Poststreptococcal reactive arthritis has been described as a new entity; however, such patients should probably receive the same attention as patients with rheumatic fever to avoid recurrences of the disease and cardiac sequelae. PMID- 8519618 TI - An update on juvenile dermatomyositis. AB - Juvenile dermatomyositis (JDMS) is a systemic vasculopathy characterized primarily by inflammation of skin and muscle. JDMS is identified in more than three per million persons per year, using established diagnostic criteria. Although originally thought to be a relatively homogeneous disease, new data confirm that heterogeneity in JDMS may be found at several levels and that each variant may be associated with a different disease course. Unlike adults with dermatomyositis, of whom more than 50% have a specific myositis-associated antibody (MSA), a much smaller number of children appear to test positive for a known MSA (about 10%), despite the evidence that more than 60% of children with JDMS test positive for antinuclear antibodies. In children, the most common MSA is directed against Mi-2, not toward one of the tRNA synthetases, such as tRNA histidine, as is found in 20% to 30% of adults with myositis. About 50% of children with JDMS have circulating evidence of endothelial cell damage (increased vWF:Ag), whereas others have different indicators of disease activity, such as elevated neopterin (> 60%) or increased circulating B cells with peripheral lymphopenia (> 80%). Newer modes of assessment of functional ability may help evaluate response to therapy. Finally, physicians with newly diagnosed (< 6 months) JDMS patients are urged to call the new National Institutes of Health Rare Disease Registry for New Onset Dermatomyositis (312-880-3333) to enroll their patients and for more information on the onset of this disease. PMID- 8519619 TI - Scleroderma and fasciitis in children. AB - Scleroderma is a spectrum of disorders, all of which may occur in childhood. Childhood disease differs from adult disease in that localized forms predominate, with major problems confined to the skin and underlying soft tissues; generalized scleroderma, whether diffuse or limited, is less common. Childhood eosinophilic fasciitis is rare, and the literature is scant. The pattern appears to be similar to that in adults, and as in the adult form, the overlap between eosinophilic fasciitis, morphea, and linear scleroderma is blurred. The etiopathogenesis of juvenile-onset scleroderma is unknown but almost certainly multifactorial. The heterogeneity of its clinical expression may argue for it being more than one disease. This review attempts to document the expression of scleroderma in childhood and relate it to etiologic, immunologic, and pathogenic considerations. PMID- 8519620 TI - Behcet's disease and Takayasu's disease in children. AB - Behcet's disease and Takayasu's disease in children are uncommon and may have an insidious course leading to a delayed diagnosis. Both diseases usually occur in late childhood, although disease onset in the first year of life has been reported. Compared with adults, Behcet's disease in children appears to be characterized by a lower incidence of ocular and vascular involvement, and Takayasu's disease by a higher incidence of systemic symptoms. The reported characteristics of both diseases in children are reviewed. PMID- 8519621 TI - Kawasaki syndrome. AB - Although a general consensus on the etiology of Kawasaki syndrome has not been reached, increasing evidence suggests that this illness represents a response to a superantigen. This conclusion is based on the observations of the immunologic changes that characterize the acute stages of illness as well as on the demonstrated association with toxin-producing bacteria in the pharynx and gastrointestinal tract. Therapy with intravenous gamma globulin and high-dose aspirin remains the standard of care for acute disease. Long-term follow-up of increasing numbers of children has confirmed that few properly treated children are at risk for the development of coronary artery abnormalities due to this illness. PMID- 8519622 TI - Childhood acute myeloid leukemias expressing lymphoid-associated antigens. PMID- 8519623 TI - Parotid carcinomas following the treatment of childhood acute lymphoblastic leukemia. PMID- 8519624 TI - Prognostic factors in childhood acute lymphoblastic leukemia. PMID- 8519625 TI - Influence of treatment modalities on prepubertal growth in children with acute lymphoblastic leukemia. PMID- 8519626 TI - Development of pediatric hemato-oncology in Romania. PMID- 8519627 TI - Pediatric hematology and oncology in Italy: half a century of progress, an ongoing search for improvement. AB - Pediatric hematology and oncology has been a well-organized specialty throughout Italy only since 1974. However, it seemed interesting and fitting to review some of the milestones lying at the base of the development of this field of medicine: the first Italian Children's Hospital created in Florence in the fifteenth century; the first textbook of pediatrics, De Morbis Puerorum, by G. Mercuriale of Bologna; the first hematologic breakthroughs in the seventeenth, eighteenth, and nineteenth centuries; and the paramount achievements in pediatric hematology and oncology over the last 50 years. PMID- 8519628 TI - Effect of different exposures to desferrioxamine on neuroblastoma cell lines. AB - Desferrioxamine (DFO) has shown anti-proliferative and cytotoxic effects on several tumor cells. DFO is used at present in the treatment of neuroblastoma in combination with chemotherapy (D-CECaT regimen: cyclophosphamide, etoposide, carboplatin, and thiotepa). We compared the effect of continuous or intermittent exposures to DFO on 3H-thymidine uptake, viability, and cell cycle of human neuroblastoma (NB) cell lines. Our results show that continuous exposures to DFO cause dose- and time-dependent cytotoxicity of NB cells, while intermittent exposures result in significant NB cell toxicity only when using high DFO concentrations. By 3H-thymidine uptake, a significant inhibition of proliferation was observed only in continuous exposures. In addition, a consistent arrest in G1 phase was detected only in cultures treated continuously with high DFO concentrations. Our data indicate that 3H-thymidine uptake, viability, and cell cycle changes are proportional to the extent of exposure and concentration of DFO, suggesting that in vivo DFO continuous infusion may improve anti neuroblastoma activity. PMID- 8519629 TI - Incidence of childhood lymphoma in northern Israel, 1973-1990. AB - We retrospectively analyzed all 164 cases of pediatric lymphoma diagnosed in northern Israel during the 18-year period from 1973 to 1990. Our findings generally conformed to those of other studies with regard to annual incidence (24.7/million), age at diagnosis (5 to 9 years for Jewish males, later for others), histology (Hodgkin's disease most commonly), and male predominance. The northern Israeli pediatric lymphoma pattern of incidence is similar to the Asian African-South American pattern and unlike that of Europe or North America; in Israel, lymphoma rather than brain tumor is the second most common childhood malignancy. The nodular sclerosing variant was the most common histology seen in Hodgkin's lymphoma (especially in females), followed by mixed cellularity. Malignancies are generally more common in Jewish children but lymphomas in particular were seen more often in Arabs (28.7/million), while the Ashkenasi (20.8/million) and Sephardi (21.6/million) Jewish populations had similar incidences. The high rate of consanguineous marriages among Arabs and their lower socioeconomic level may explain the high incidence of lymphomas in this group. PMID- 8519630 TI - Usefulness of red cell zinc protoporphyrin concentration in the investigation of microcytosis in children. AB - The clinical usefulness of the measurement of red cell zinc protoporphyrin (ZPP), an indicator of iron-deficient erythropoiesis, was assessed in a group of UK children undergoing investigation for red cell microcytosis. Of 213 children studied, 136 had increased ZPP values. Of these, 86 also had reduced iron stores as indicated by serum ferritin concentration. The 50 children with increased ZPP and normal ferritin values could be divided into two main groups. One group comprised 28 children who had evidence of coexistent infection or inflammatory disease. The other included 21 children who had beta-thalassemia trait (n = 19) or disease (n = 2). Among the 77 children with normal ZPP values, 22 had reduced serum ferritin concentrations and 45 did not, nor did they have evidence of beta thalassemia. Microcytosis in some of these children could have been due to alpha thalassemia trait. Measurement of ZPP is a simple, quick, and relatively cheap method of confirming the presence of iron-deficient erythropoiesis even when inflammation makes serum ferritin measurements unreliable. It is not as sensitive as the ferritin assay to the early stages of iron deficiency, and its specificity is reduced by the occurrence of raised values in most children with beta thalassemia trait. Where there is microcytosis, normal values, together with normal hemoglobin A2 and serum ferritin concentrations, are likely to indicate alpha-thalassemia trait. PMID- 8519631 TI - Clinical significance of childhood acute myeloid leukemias expressing lymphoid associated antigens. AB - The clinical significance of the expression of lymphoid-associated antigens in leukemic cells was studied in 66 children with newly diagnosed acute myeloid leukemia (AML). Among 66 AML cases, 17% were CD7-positive, 15% were CD19 positive, 8% were CD2-positive, and 5% were CD10-positive. In 23 (35%) of the 66 AML cases, at least one lymphoid-associated antigen was expressed in the leukemic cells. When the clinical features and laboratory findings were compared at diagnosis between the 23 Ly+ and the 43 Ly- AML cases, no statistically significant difference was found. The expression of CD34 was significantly more frequent in Ly+ AML cases (91%) than in Ly- AML cases (31%). Chromosomal analysis revealed t(8;21) in 6 of the 21 Ly+ AML cases examined. No other specific chromosome aberration was noted. The 3-year event-free survival rates of Ly+ AML cases and Ly- AML cases were 34% +/- 12% and 26% +/- 8%, respectively. There was no statistically significant difference between the two groups. Further studies are required to determine the prognostic significance of lymphoid-associated antigen expression. PMID- 8519632 TI - Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure. AB - We report on an 18.5-year-old woman with osteosarcoma and delayed methotrexate (MTX) elimination due to renal failure after high-dose MTX, in whom rescue with high doses of folinic acid caused intolerable side effects. In this life threatening clinical situation, the patients was rescued by the administration of recombinant carboxypeptidase G2, a bacterial enzyme that rapidly hydrolyzes MTX into inactive metabolites. This is the first report on the successful clinical use of this alternative catabolic route for the elimination of MTX. PMID- 8519633 TI - Prevention of emesis by tropisetron in children receiving combined chemotherapy with cisplatin. AB - We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its use in 15 children with malignant disease who received cisplatin (CDDP) either alone (1/15) or in combination (14/15) with other cytostatic drugs. Tropisetron was given to 15 children (8 boys and 7 girls, ranging from 6 months to 17 years of age) with miscellaneous neoplasms. Generally, tropisetron (5 mg/m2/day, maximum 5 mg/day) was administered intravenously the first day of CDDP based chemotherapy and orally for 4 subsequent days of chemotherapy. The dose of tropisetron was reduced to 0.2 mg/kg/day in children less than 1 year of age and/or those weighing less than 10 kg. Vomiting and nausea were controlled completely in 8 of 15 (53.3%) children on day 1 with a single intravenous infusion of tropisetron. Partial control was observed in 40% of patients on day 1. Complete control of delayed nausea and vomiting ranged between 40% and 80% in patients over days 2 to 5. The results obtained during administration of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of malignant disease in pediatric patients. PMID- 8519634 TI - Intra-abdominal bleeding in a 14-year-old girl with acute immune thrombocytopenic purpura. AB - We describe a 14-year-old girl with acute immune thrombocytopenic purpura. She presented with acute abdominal pain, and her hematocrit decreased from 44% to 29%. The bleeding was due to the rupture of a distended follicle on about the 14th day of her menstrual cycle. The patient's low platelet count made possible the continuous oozing of blood from the follicle into the abdominal cavity, causing peritoneal irritation and the fall in hematocrit. She received treatment with intravenous Ig. This case indicates that unnecessary surgery can be avoided if there is reason to believe that the cause of internal bleeding does not require surgical intervention. PMID- 8519635 TI - Effect of interferon-alpha therapy in a patient with common variable immunodeficiency and chronic Epstein-Barr virus infection. AB - We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was detected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-alpha (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-alpha is a valid alternative in therapy of immunodeficient EB virus-infected patients. PMID- 8519636 TI - AIDS-resembling disease in a non-HIV-infected African born to an HIV-positive mother. AB - We report the case of a 10-month-old boy born to an HIV-positive mother who presented with symptoms compatible with AIDS. However, he became HIV-negative and his condition was probably due to combined cytomegalovirus and Epstein-Barr virus infections. PMID- 8519637 TI - p53 codon 213 (A-G) polymorphism in a Turkish population. AB - We studied a rare polymorphism at exon 6 (CD 213) of the p53 gene in a healthy Turkish population (n = 26) and in Turks with different types of tumors such as malignant lymphoma (n = 12), osteosarcoma (n = 5), and nasopharyngeal sarcoma (n = 4). The polymorphic allele was found in only one of the malignant lymphoma patients (4.16%). Our data revealed that CD 213 (A-G) polymorphism is very rare in the Turkish population and there is no association with the tumors. PMID- 8519638 TI - Postvaccinal thrombocytopenia: fact or myth? PMID- 8519639 TI - Incidence of parvovirus B19 infection among thalassemia major patients from Ankara, Turkey. PMID- 8519640 TI - Biology and pharmacology of thiopurines. PMID- 8519641 TI - Zoonoses control. Diagnosis and surveillance of Lyme borreliosis in humans. PMID- 8519642 TI - Brucellosis associated with unpasteurized milk products abroad. PMID- 8519643 TI - Hazards of ionising radiation: 100 years of observations on man. AB - In November 1895, when Conrad Rontgen serendipitously discovered X-rays, epidemiology was effectively limited to the study of infectious disease. What little epidemiological work was done in other fields was done as part of clinical medicine or under the heading of geographical pathology. The risks from exposure to X-rays and subsequently from other types of ionising radiation were consequently discovered by qualitative association or animal experiment. They did not begin to be quantified in humans until half a century later, when epidemiology emerged as a scientific discipline capable of quantifying risks of non-infectious disease and the scientific world was alerted to the need for assessing the effects of the radiation to which large populations might be exposed by the use of nuclear energy in peace and war. PMID- 8519644 TI - Is mucinous carcinoma of the colorectum a distinct genetic entity? AB - Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group. PMID- 8519645 TI - Plasma clearance of an antibody--enzyme conjugate in ADEPT by monoclonal anti enzyme: its effect on prodrug activation in vivo. AB - The effect of anti-enzyme antibody clearance on prodrug turnover in antibody directed enzyme prodrug therapy (ADEPT) has been studied. Mice bearing LS174T xenografts were given localising carboxypeptidase G2 (CPG)2 conjugate (AEC) and 19 h later galactosylated anti-CPG2 antibody (SB43-GAL). In regimen I prodrug was injected 5 h after SB43-GAL as previously described. In regimen 2 and 3 a shortened and extended clearance time was used in which prodrug was administered 0.5 h or 53 h after SB43-GAL respectively. Regimen 1 resulted in similar tumour and normal tissue levels of active drug to those of the control in which prodrug was given 72 h after AEC. SB43-GAL therefore accelerated clearance of enzyme allowing early administration of prodrug. In regimen 2, very high active drug levels were found in the liver, showing removal of AEC from the blood followed by reactivation of enzyme and extensive and rapid prodrug turnover. Active drug levels in tumour and blood reached similar peak levels to those of the control. Regimen 3 resulted in lower active drug levels in tissues, consistent with degradation and excretion of enzyme. Regimen 3 also produced the best tumour to normal ratios for active drug. Residual prodrug in tumour was unaffected by SB43 GAL, showing the advantage of galactosylation in minimising inactivation of CPG2 in tumour. By contrast, residual prodrug in blood persisted for longer when SB43 GAL was used. Circulatory clearance of enzyme with SB43-GAL allows prodrug to be administered expediently with reduced toxicity and with the prospect of increasing the dosage. PMID- 8519646 TI - Preparation and preclinical evaluation of humanised A33 immunoconjugates for radioimmunotherapy. AB - A humanised IgG1/k version of A33 (hA33) has been constructed and expressed with yields up to 700 mg l-1 in mouse myeloma NS0 cells in suspension culture. The equilibrium dissociation constant of hA33 (KD = 1.3 nM) was shown to be equivalent to that of the murine antibody in a cell-binding assay. hA33 labelled with yttrium-90 using the macrocyclic chelator 12N4 (DOTA) was shown to localise very effectively to human colon tumour xenografts in nude mice, with tumour levels increasing as blood concentration fell up to 144 h. A Fab' variant of hA33 with a single hinge thiol group to facilitate chemical cross-linking has also been constructed and expressed with yields of 500 mg l-1. Trimaleimide cross linkers have been used to produce a trivalent Fab fragment (hA33 TFM) that binds antigen on tumour cells with greater avidity than hA33 IgG. Cross-linkers incorporating 12N4 or 9N3 macrocycles have been used to produce hA33 TFM labelled stably and site specifically with yttrium-90 or indium-111 respectively. These molecules have been used to demonstrate that hA33 TFM is cleared more rapidly than hA33 IgG from the circulation of animals but does not lead to accumulation of these metallic radionuclides in the kidney. 90Y-labelled hA33 TFM therefore appears to be the optimal form of the antibody for radioimmunotherapy of colorectal carcinoma. PMID- 8519647 TI - Preclinical studies with the anti-CD19-saporin immunotoxin BU12-SAPORIN for the treatment of human-B-cell tumours. AB - The immunotoxin BU12-SAPORIN was constructed by covalently coupling the single chain ribosome-inactivating protein saporin to the anti-CD19 monoclonal antibody BU12 via a disulphide linker using the heterobifunctional reagent SPDP. The immunoreactivity and specificity of BU12-SAPORIN was identical to that of unmodified native BU12 antibody. BU12-SAPORIN was selectively cytotoxic in vitro in a dose-dependent manner for the CD19+ human common acute lymphoblastic leukaemia (cALL) cell line NALM-6 but exhibited no toxicity for the CD19- T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2. The survival of severe combined immunodeficient (SCID) mice with disseminated NALM-6 leukaemia was significantly prolonged compared with sham-treated control animals by a course of therapy with BU12-SAPORIN but not with the irrelevant anti-CD7 immunotoxin HB2 SAPORIN. BU12-SAPORIN had no therapeutic effect in SCID mice with disseminated CD19- HSB-2 leukaemia. These preclinical studies have clearly demonstrated the selective cytotoxicity of BU12-SAPORIN for CD19+ target cells both in vitro and in vivo. This, taken together with the lack of expression of the CD19 molecule by any normal life-sustaining tissue and its ubiquitous and homogeneous expression by the majority of cALL and B-NHL cells, provides the rationale for undertaking a phase I trial of systemic therapy with BU12-SAPORIN. PMID- 8519648 TI - Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. AB - Certain anti-cancer agents are known to induce apoptosis in human tumour cells. However, these agents are intrinsically cytotoxic against cells of normal tissue origin, including myelocytes and immunocytes. Here we show that a naturally occurring flavone of citrus origin, tangeretin (5,6,7,8,4'-pentamethoxyflavone), induces apoptosis in human promyelocytic leukaemia HL-60 cells, whereas the flavone showed no cytotoxicity against human peripheral blood mononuclear cells (PBMCs). The growth of HL-60 cells in vitro assessed by [3H]thymidine incorporation or tetrazolium crystal formation was strongly suppressed in the presence of tangeretin; the IC50 values range between 0.062 and 0.173 microM. Apoptosis of HL-60 cells, assessed by cell morphology and DNA fragmentation, was demonstrated in the presence of > 2.7 microM tangeretin. Flow cytometric analysis of tangeretin-treated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G1 cells and a concomitant increase of S and/or G2/M cells. Apoptosis was evident after 24 h of incubation with tangeretin, and the tangeretin effect as assessed by DNA fragmentation or growth inhibition was significantly attenuated in the presence of Zn2+, which is known to inhibit Ca(2+)-dependent endonuclease activity. Ca2+ and Mg2+, in contrast, promoted the effect of tangeretin. Cycloheximide significantly decreased the tangeretin effect on HL-60 cell growth, suggesting that protein synthesis is required for flavonoid induced apoptosis. Tangeretin showed no cytotoxicity against either HL-60 cells or mitogen-activated PBMCs even at high concentration (27 microM) as determined by a dye exclusion test. Moreover, the flavonoid was less effective on growth of human T-lymphocytic leukaemia MOLT-4 cells or on blastogenesis of PBMCs. These results suggest that tangeretin inhibits growth of HL-60 cells in vitro, partially through induction of apoptosis, without causing serious side-effects on immune cells. PMID- 8519649 TI - Differences in resistance to 5-fluorouracil as a function of cell cycle delay and not apoptosis. AB - A series of human embryo fibroblasts has previously been shown to display increasing resistance to the antimetabolites methotrexate (MTX) and N phosphonacetyl-L-aspartate (PALA) with increasing tumorigenicity. This increased resistance was found to be further increased as a result of salvage pathway activity for purine and pyrimidine biosynthesis. A similar pattern of increasing resistance paralleling increasing tumorigenicity has now been shown to occur with 5-fluorouracil (5-FU), which is independent of salvage pathway activity. The KMS normal cell line was found to be more sensitive to 5-FU than either the immortalised KMST or tumorigenic KN-NM cell lines. Immunohistochemical analysis of the three cell lines demonstrated high levels of p53 protein in the KMST and KN-NM cell lines, but undetectable p53 levels in the KMS cell line. From these data it was hypothesised that a difference in p53 function may be causing the difference in the patterns of sensitivity observed in the three cell lines. P53 is now believed to function as a regulator of a G1 to S cell cycle checkpoint and as an inducer of apoptosis following DNA damage to the cell. The differences in sensitivity of the cell lines could not be explained by differences in the levels of apoptosis but could be attributed to differences in cell cycle response. Our evidence suggests that loss of cell cycle control, possibly through loss of p53 function, is an important factor in increasing the drug resistance of fibroblast cell lines. PMID- 8519650 TI - Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas. AB - Nerve growth factor (NGF) administration to athymic mice with transplanted human bromocriptine-resistant prolactinoma, results in the expression of dopamine D-2 receptors in the tumour and restores sensitivity to subsequent treatment with bromocriptine, which then produces normalisation of plasma prolactin and tumour regression. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine. PMID- 8519651 TI - Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane. AB - The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP Cl) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm 1. However, only DDP-OH was observed to bind to the phosphate group (PO(-)2). The binding of either drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains were increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains. PMID- 8519652 TI - Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines. AB - The interaction between moderate-dose radiation and cisplatin or carboplatin was studied in a cisplatin-sensitive (GLC4) and -resistant (GLC4-CDDP) human small cell lung cancer cell line. Cellular toxicity was analysed under oxic conditions with the microculture tetrazolium assay. For the platinum and radiation toxicity with the clinically relevant dose ranges applied, this assay was used to obtain information on cell survival after the treatments. Apart from effects on cell survival effects on DNA were also investigated. Configurational DNA changes could be induced by platinum drugs and thereby these drugs might change the frequency of DNA double-strand breaks (dsbs). DNA fragmentation assayed with the clamped homogeneous electric field (CHEF) technique was used as a measure for dsbs in DNA. The radiosensitising effect of the platinum drugs was expressed as enhancement ratio (ER) calculated directly from survival levels of the initial slope of the curve. The highest ER for cisplatin in GLC4 was 1.39 and in GLC4 CDDP 1.38. These were all at 75% cell survival. Carboplatin showed increased enhancement with prolonged incubation up to 1.21 in GLC4 and was equally effective as cisplatin in GLC4-CDDP. According to isobologram analysis, prolonged incubation with both platinum drugs showed at least additivity with radiation for both cell lines at clinically achievable doses. GLC4-CDDP showed cross-resistance to radiation. The radiosensitising capacity of both lung cancer cell lines was not dependent on their platinum sensitivity. The formation of dsbs in DNA directly after radiation was not influenced by pretreatment of either drug in the sensitive or in the resistant cell line. Drug treatment resulted in decreased DNA extractability in control as well as in irradiated cells. Modest enhancement ratio for radiosensitisation by platinum drugs cannot be explained on the level of dsb formation in DNA in both cell lines. Interaction of radiation with the clinically less toxic carboplatin can be improved by prolonged low-dose carboplatin exposure before irradiation and is as potent as cisplatin in the resistant lung cancer cell line. This suggests an advantage in combining radiation and carboplatin in lung cancer patients. PMID- 8519653 TI - Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators. AB - Malignant human breast tumours contain high levels of prostaglandin E2 (PGE2). However, the mechanisms controlling PGE2 production in breast cancer are unknown. This in vitro study investigates the capacity for PGE2 synthesis and metabolism in several human breast cancer cell lines and early passage human breast fibroblasts and seeks to identify potential regulatory factors which may control these pathways. Basal PGE2 production rose up to 30-fold in breast fibroblast lines on addition of exogenous arachidonic acid (10 microM), whereas no such changes were observed in six out of seven cancer cell lines, with the exception of modest increases in MDA-MB-231 cells. Interleukin 1 beta (IL-1 beta) also induced PGE2 production in breast fibroblasts in the presence of excess substrate, consistent with cyclo-oxygenase induction by the cytokine. Under these conditions only Hs578T cells and MDA-MB-231 cells demonstrated large increases in PGE2 in response to IL-1 beta or phorbol ester; no such responses were seen in MCF-7, T47-D, ZR-75-1, BT-20 or CLF-90-1 cells. In the absence of added arachidonate, bradykinin (BK) and endothelin-1 (ET-1), potentiated PGE2 production in IL-1 beta-treated fibroblasts, possibly by mobilising endogenous substrate. PGE2 also stimulated ET-1 production by breast cancer cells. In co cultures with T47-D cells both basal and stimulated PGE2 production by breast fibroblasts was greatly reduced. This appeared to be due to metabolic inactivation by the cancer cell since T47-D cells readily converted PGE2 to 15 keto-PGE2. This apparent 15-hydroxy-PG dehydrogenase activity was stimulated by TPA and inhibited by cycloheximide. In conclusion, breast fibroblasts, particularly under the influence of inflammatory mediators, provide a potentially rich source for PGE2 production in breast tumours, whereas significant contributions from the epithelial tumour component may be restricted to cancer cells exhibiting an invasive phenotype. Metabolic inactivation by the cancer cells may also play an important role in the regulation of breast tumour PGE2 levels. PMID- 8519654 TI - Expression of fibroblast growth factor 1 is lower in breast cancer than in the normal human breast. AB - We have measured the amount of fibroblast growth factor 1 (FGF-1) mRNA and protein in primary breast cancers and non-malignant breast tissue and have found greatly reduced levels in breast cancer compared with non-malignant tissue. A total of 116 breast cancers and 37 biopsies taken from non-malignant breast were compared for FGF-1 mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and significantly lower levels were found in the cancer tissues (P < 0.001). These findings were confirmed at the protein level where four out of five breast cancers contained no detectable FGF-1 and a fifth cancer had a low level of FGF-1 compared with three samples from reduction mammoplasties. Similar results were obtained from breast cell lines in which 80% of cancer cell lines had very low levels of FGF-1, whereas all non-malignant breast cell lines contained higher levels of FGF-1. Immunohistochemical analysis indicated that FGF 1 was present in the luminal epithelial cells of the non-malignant breast but was absent from cancer cells. The decreased levels of FGF-1 in breast cancer may indicate that stimulation of cancer cells is resulting in down-regulation of FGF 1 expression or may implicate FGF-1 as a differentiation factor rather than a growth factor at its physiological concentration in the breast. PMID- 8519655 TI - Determination of oestrogen responsiveness of breast cancer by competitive reverse transcription-polymerase chain reaction. AB - Competitive polymerase chain reaction assays have been developed for the quantitation of oestrogen receptor mRNA and two oestrogen-regulated mRNAs (progesterone receptor and pNR-2/pS2) in breast cancer cells. These assays are more sensitive than traditional hybridisation techniques, do not require the use of radioisotopes, measure absolute amounts of messenger RNAs and can be used to measure the expression of mRNAs in small numbers of tumour cells obtained by fine needle aspiration (FNA). These assays should prove useful for predicting the hormone responsiveness of breast cancer from tumour cells obtained by FNA at diagnosis and could be particularly useful in the management of elderly/frail patients who receive primary tamoxifen, or in other patients for whom tumour tissue for standard biochemical measurements is not available. PMID- 8519656 TI - Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. AB - Melatonin (aMT) appears to be a potentially important oncostatic substance that can block the mitogenic effects of tumour-promoting hormones and growth factors such as oestradiol and epidermal growth factor, in vitro. In the present study, we examined the possibility that aMT would also inhibit the stimulatory effects of the tumour-promoter prolactin (PRL) on MCF-7 and ZR75-1 human breast cancer cell (HBC) growth under 5% charcoal-stripped fetal bovine serum culture conditions. Human PRL (10-100 ng ml-1) stimulated the rate of MCF-7 and ZR-75-1 HBC growth up to 2-fold above that of untreated controls. Melatonin, at concentrations between 10(-12) M and 10(-5)M, diminished and at physiological levels completely abolished PRL's mitogenic activity, but had no effect on growth in the absence of PRL. The mitogenic effects of human growth hormone (hGH), a PRL related hormone, and also of several monoclonal antibodies (MAbs) against the PRL receptor (PRLR), were also abrogated by physiological concentrations of aMT. Additionally, aMT blocked the enhancement of MAb mitogenic activity induced by a second 'cross-linking' antibody (CLA). These findings indicate that aMT interrupts the PRLR-mediated growth signal in HBC and suggest that the oncostatic activity of aMT may also be linked with an antagonism of PRL's actions. PMID- 8519657 TI - Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells. AB - Previously we have shown that tamoxifen (TAM) induces morphological and biochemical changes typical of apoptosis in oestrogen receptor (ER)-positive MCF 7 or ER-negative MDA-231 human breast cancer cells. In this study the effects of TAM on expression of transforming growth factor beta 1 (TGF-beta 1) were correlated with the effects on cell cycle kinetics and apoptosis. TAM had similar biphasic effects on both cell lines. Short-term (< 6 h) TAM incubation resulted in a slight decrease in TGF-beta 1 protein despite an increase in TGF-beta 1 mRNA and was associated with an increase in cells in S-phase. No apoptotic effects were noted. Longer (> or = 12 h) TAM incubation induced TGF-beta 1 protein (about 3-fold) and mRNA expression (about 2-fold) in both cell lines, and was associated with G1/G0 blockade and induction of apoptosis. The accumulation of TAM-induced TGF-beta 1 mRNA was increased by cycloheximide, but was not affected by 17 beta oestradiol. Long-term incubation with TAM had no significant effect on TGF-beta 1 gene copy number. TAM-induced internucleosomal DNA cleavage was inhibited in both cell lines by the addition of an anti-TGF-beta 1 antibody. TAM has dose- and time dependent effects on TGF-beta 1 expression associated with changes in cell cycle kinetics. These effects are independent of ER status and may be the result of a direct regulatory effect of TAM on TGF-beta 1 transcription. It also appears that induction of TGF-beta 1 plays an important role in TAM-induced apoptosis in breast cancer cells. PMID- 8519658 TI - Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid. AB - All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E cadherin/catenin complex was shown to be the most probable mechanism of the anti invasive action. We did a series of experiments to determine whether the anti invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action. PMID- 8519659 TI - Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines. AB - Topoisomerase II is a key target for many anti-cancer drugs used to treat breast cancer. In human cells there are two closely related, but differentially expressed, topoisomerase II isoforms, designated topoisomerase II alpha and beta. Here, we report the production of a new polyclonal antibody raised against a fragment of the C-terminal domain of the 180 kDa form of topoisomerase II (the beta isoform), which does not cross-react with the 170 kDa form (the alpha isoform). Using this antibody, together with a polyclonal antibody specific for the 170 kDa isoform of topoisomerase II, we have examined the relationship between the sensitivity of a panel of human breast cancer cell lines to different classes of topoisomerase II inhibitors and cellular levels of the topoisomerase II alpha and beta proteins. We found that sensitivity to amsacrine showed a correlation with the level of expression of topoisomerase II alpha protein, and that sensitivity to etoposide showed a similar correlation with the level of expression of topoisomerase II beta protein. There was also a relationship between sensitivity of these cell lines to mitoxantrone and the cellular level of both isoforms of topoisomerase II. No relationship was found between the level of mRNA for topoisomerase II alpha or beta, and either sensitivity of breast cancer cell lines to topoisomerase II inhibitors or the level of topoisomerase II protein expression. PMID- 8519660 TI - Pharmacokinetics and binding of the bioreductive probe for hypoxia, NITP: effect of route of administration. AB - The novel compound 7(-)[4'-(2-nitroimidazol-l-yl)-butyl]-theophylline (NITP) can be used as an immunologically detectable probe for hypoxic cells. Because of the limited water solubility of NITP, it has been administered dissolved in peanut oil with 10% dimethylsulphoxide (DMSO). A new aqueous formulation has been devised, based on a 50% solution of a modified beta-cyclodextrin (Molecusol HPB), which increases the water solubility of NITP 10-fold. The pharmacokinetics of NITP in plasma and tumours have been compared following oral and intraperitoneal (i.p.) administration of the NITP in Molecusol, i.p. administration of NITP dissolved in peanut oil + 10% DMSO and injection of a near-saturated aqueous solution of the drug intravenously via the tail vein or i.p. or directly into the tumours. Binding of the marker to hypoxic cells within tumours was also measured after the different routes of administration. The Molecusol vehicle was unexpectedly toxic when administered i.p., but there was no toxicity from NITP dissolved in Molecusol when administered orally. Binding of the drug within tumours was seen for both the peanut oil + 10% DMSO and Molecusol formulations and for both oral and intraperitoneal routes. Binding of NITP within tumours has also been observed following direct injection of the drug, with minimal whole body exposure to NITP. However, the bound metabolites of NITP within tumours were localised to the injection site, suggesting that direct injection is unlikely to be a useful method of administering bioreductive hypoxia markers. The data in this paper demonstrate that bound metabolites of the hypoxia marker NITP can be detected in tumours following oral administration of an aqueous formulation of NITP, and suggest that oral administration could be a satisfactory administration route for clinical studies with NITP. PMID- 8519661 TI - Expression of nm23-H1 and nm23-H2 protein in endometrial carcinoma. AB - nm23 gene expression has been shown to be inversely correlated with tumour metastatic potential in some cancers but not in others. Examination was made of the expression of nm23-H1 and nm23-H2 gene products by immunohistochemistry and immunoblotting in 28 endometrial carcinomas. Immunohistochemistry indicated the cytoplasm of cancer cells to be positive, and myometrium and endometrial stromal cells negative, for nm23-H1 and -H2 protein. The staining intensity for these proteins was significantly stronger in well-differentiated adenocarcinomas (G1) than in those moderately differentiated (G2) (P < 0.05). nm23-H1 and -H2 proteins were shown by immunoblotting to be present at significantly higher levels in G1 than in G2 tumours (P < 0.05). Two of eight cases expressed high nm23-H1 and -H2 protein in poorly differentiated adenocarcinomas (G3). In G3 tumours, nm23 expression may be diverse. In this study, the expression of nm23-H1 and -H2 was not correlated with stage, metastasis, tumour size, myometrial invasion, oestrogen receptor, progesterone receptor or menopause. It follows from the findings presented above that the high expression of nm23-H1 and -H2 is positively correlated with histological differentiation. PMID- 8519663 TI - Cytotoxic effect of RB 6145 in human tumour cell lines: dependence on hypoxia, extra- and intracellular pH and drug uptake. AB - Low pH and hypoxia are a common feature of many solid tumours. This study examined the effect of these two conditions on the cytotoxic properties of the bifunctional agent RB 6145, the prodrug of RSU 1069. The effect of acidic pH on RB 6145 toxicity was examined in six human tumour cell lines under hypoxic conditions and was found to have little effect in HT 29, A549, U373 and HT 144 cells. Treatment was for 1 h at 37 degrees C, pH 6.4 or 7.4. Significant potentiation of RB 6145 toxicity was observed in SiHa cells (enhancement ratio; ERpH approximately 1.6) and in U1 cells (ERpH approximately 1.4). In these two cell lines the potentiation of RB 6145 toxicity arising from hypoxia was large, with ERHyp approximately 11 and 15 in SiHa and U1 cells respectively. SiHa cells, which show a pH effect and HT 29 cells, which do not, were chosen for further comparative studies of drug uptake )nd regulation of intracellular pH. High performance liquid chromatography (HPLC) determinations of the uptake of RB 6145 and its dervatives showed that in SiHa cells, intracellular to extracellular drug concentration ratio (Ci/Ce) at 1 h was approximately 40% higher at pH 6.4 than at pH 7.4, whereas in HT 29 cells Ci/Ce was approximately 25% lower. Under conditions of acidic extracellular pH, regulation of pH was somewhat less effective in SiHa cells, where pHi dropped to within 0.2 pH units of the extracellular pH over a 2.5 h treatment at pH 6.4. It seems likely that increased drug uptake was at least part of the basis for the observed potentiation of RB 6145 toxicity in SiHa cells. A model which would better explain the results for both cell lines might also include the possibility that low pH per se potentiates cytotoxic damage to a modest extent and that it is offset or augmented by altered uptake in HT 29 and SiHa cells respectively. PMID- 8519662 TI - Direct evidence that hydralazine can induce hypoxia in both transplanted and spontaneous murine tumours. AB - Hydralazine can substantially decrease blood flow and increase hypoxia in transplanted tumours. Previous indirect studies have suggested that hydralazine does not induce such effects in spontaneous tumours. We have now directly investigated the ability of hydralazine to increase hypoxia in both transplanted and spontaneous murine tumours by measuring tumour oxygen partial pressure (pO2) distributions using an Eppendorf oxygen electrode. Spontaneous tumours arose at different sites in CDF1 mice, while transplanted tumours were produced by implanting a C3H mouse mammary carcinoma on the backs of the same mouse strain. Measurements of pO2 were made in anaesthetised mice immediately before and 45 min after an intravenous injection of 5 mg kg-1 hydralazine. In the transplanted tumours hydralazine significantly decreased tumour oxygenation, such that the percentage of pO2 values < or = 5 mmHg increased from 45% to 87%, and median pO2 decreased from 5 to 3 mmHg. Similar significant changes were induced by hydralazine in the spontaneous tumours, the percentage of pO2 values < or = 5 mmHg increasing from 60% to 94% while the median pO2 values decreased from 8 to 2 mmHg. These results clearly show that there is no difference in the response of transplanted and spontaneous mouse tumours to hydralazine. PMID- 8519664 TI - A sensitive enzyme-linked immunosorbent assay used for quantitation of epidermal growth factor receptor protein in head and neck carcinomas: evaluation, interpretations and limitations. AB - The EGF receptor is a transmembrane glycoprotein exerting mitogenic effects on epithelial cells. The purpose of the present study was to develop a sensitive enzyme-linked immunosorbent assay (ELISA) for determination of the epidermal growth factor receptor (EGFR) protein to examine whether the receptor was overexpressed in head and neck squamous cell carcinomas compared with the normal counterpart, and to establish whether clinicopathological correlations were present by investigating a broad spectrum of parameters (tumour size, clinical stage, positive lymph nodes, tumour site, histological grade, keratinisation, preoperative irradiation and clinical outcome). The assay employs two commercially available monoclonal antibodies, both detecting protein epitopes. The material comprises 60 head and neck carcinomas, corresponding normal tissue and normal oral mucosa from healthy individuals. The study demonstrates significantly higher receptor levels in tumours compared with normal tissue (P < 0.002) and a range in tumours and normal tissues of 0.4-10.5 and 0.1-4.3 nmol g-1 membrane protein respectively. Quantitation of receptors in normal mucosa emphasises the importance of using the patients' corresponding normal tissue, because using the patients' mucosa resulted in 83% overexpression, while using normal mucosa from healthy individuals only demonstrated overexpression in 50% of cases. No significant clinicopathological correlations could be established, although the mean values for EGFR increased with tumour size and advanced clinical stage. Furthermore, the prognostic value concerning disease-free survival, recurrence and the time interval for recurrence were investigated but no significance could be demonstrated. In conclusion, the investigation supports the theory of overexpression of EGFR protein as a common motif for malignant epithelial tumours, but limitations in interpretations are demonstrated and discussed further. PMID- 8519665 TI - Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer. AB - The surface glycoprotein CD44 is widely distributed in different tissues. In contrast to healthy tissue, tumour samples show a more complex pattern of CD44 expression, indicating a loss of splice control. Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status. We evaluated the surface expression of CD44 isoforms in 22 ovarian cancer patients by means of immunohistochemistry. Additionally, we investigated 134 serological samples of these patients for the occurrence of CD44 isoform expression. For CD44 standard, CD44v5 and CF44v6 mean serum levels in patients with clinically detectable or non detectable ovarian cancer were 422.4 +/- 143.8 ng ml-1 and 547.4 +/- 148.2 ng ml 1, 12.3 +/- 7.9 ng ml-1 and 21.9 +/- 12.2 ng ml-1 and 105.5 +/- 37.9 ng ml-1 and 144.9 +/- 50.9 ng ml-1 respectively (P-values not significant). CD44 surface proteins containing epitopes encoded by splice variants CD44v5, CD44v6 and CD44v7 8 were immunohistochemically detected in 9% (n = 2), 13% (n = 3) and 4% (n = 1) of the 22 tumour samples respectively. In the present study we showed that in ovarian cancer CD44 isoforms CD44v5 and CD44v6 are expressed in very low amounts by the tumours. In accordance with this, we found that the presence of tumour is not associated with higher serum levels of CD44standard, CD44v5 and CD44v6 in preoperative serum samples in ovarian cancer patients. PMID- 8519666 TI - Enhanced lymphokine-activated killer cell activity by an immunomodulator, Roquinimex. AB - Roquinimex (Roq) is an immunomodulator known to stimulate cellular immune responses. It is currently used for immunotherapy after bone marrow transplantation (BMT). One of the major features of this compound is an enhancement of natural killer (NK) cell activity and numbers. We studied the in vitro effect of Roq on human peripheral blood NK and adherent lymphokine activated killer cell (ALAK) activities. In cultures supplemented with recombinant interleukin 2 (rIL-2) (1000 U ml-1) and Roq a significant increase in NK and LAK function was observed without a parallel increase in cell numbers. We also examined the generation of NK cells from human bone marrow (BM) immature progenitors, obtained by purging with 4-hydroperoxycyclophosphamide (4HC). NK cell numbers and activity were both increased when cultures with rIL-2 (10 U ml 1) were supplemented with Roq. These results confirm findings obtained in vivo and in vitro in the murine system and suggest that Roq is an active agent on these lymphoid populations. These properties and good tolerability make Roq an attractive tool for immunotherapy. PMID- 8519667 TI - Decreased tyrosine phosphorylation in tumour cells resistant to FCE 24517 (tallimustine). AB - Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s). PMID- 8519668 TI - Can mood disorder in women with breast cancer be identified preoperatively? AB - The Hospital Anxiety and Depression (HAD) scale, a self-report questionnaire, was tested as a method of identifying mood disorder among patients with operable breast cancer during the year after diagnosis. In a cohort of 91 patients anxiety and depression were assessed preoperatively, and at 3 and 12 months post operatively, using a standardised psychiatric interview and diagnostic rating criteria. The patients also completed the HAD scale at each assessment. Fifty out of 91 (55%) patients were full or borderline cases of depression and/or anxiety at one or more assessment points. Using a receiver operator characteristic curve analysis, the optimum threshold for the preoperative HAD scale total score to identify psychiatric disorder either preoperatively or at 3 and 12 months post operatively was 11. With this threshold 70% of both full and borderline cases occurring at any of the assessment points were correctly identified. The false positive rate was 12%. This approach was particularly sensitive to full cases, correctly identifying 90% of them. The potential for the preoperative HAD scale total score to identify mood disorder in the year after diagnosis was influenced by age. Among women aged less than 50 years, a preoperative HAD scale total score > or = 11 provided a highly sensitive indicator of mood disorder (full and borderline cases) at any time in the year after diagnosis (sensitivity = 90%). The false-positive rate was 40%. Among women older than 50 who experienced a mood disorder, only 57% were correctly identified by a HAD scale total score of > or = 11 (sensitivity = 57%). However, the false-positive rate among older women was low (3%). This simple preoperative screening approach can be used to identify patients who have or are at high risk of developing severe mood disorder in the year after diagnosis. The HAD scale is also sensitive to the detection of borderline mood disorder in patients under the age of 50. It is a specific screening tool among patients over 50, but is not sensitive to the detection of borderline mood disorder in this age group. PMID- 8519669 TI - Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials. AB - The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor. PMID- 8519670 TI - Rationale for extensive lymphadenectomy in early gastric carcinoma. AB - The incidence of nodal metastasis in early gastric carcinoma (EGC) is 10-20%. However, the optimal nodal dissection for early gastric carcinoma has not been established. A retrospective study was conducted in 392 consecutive patients who underwent potentially curative distal gastrectomy for EGC between 1962 and 1990. Of these 295 patients treated after September 1972 were prospectively entered into an extensive lymphadenectomy protocol. These patients were compared with 97 patients with simple gastrectomy in respect of the causes of death after surgery and the 10 year disease-specific survival rate. The incidence of nodal metastasis in early gastric carcinoma patients was 13.0%. Operative mortality from extensive lymphadenectomy was almost the same as from simple gastrectomy (2.0% and 2.1% respectively). Extensive lymphadenectomy provided a significantly higher 10 year survival rate than limited lymph node dissection (97.9% vs 88.1% respectively; P < 0.005). Among patients with nodal metastasis, the survival rate following extensive lymphadenectomy was significantly higher than that after simple gastrectomy (87.5% vs 55.6%; P = 0.018). Among patients without nodal metastasis, there was no difference between the two groups in the survival rate (99.4% and 96.7% respectively; P = 0.12). Multivariate analysis using the Cox proportional hazards model disclosed two significant independent prognostic factors on disease specific survival, the nodal involvement (risk ratio: 8.4; P < 0.0001) and the extent of lymph node dissection (risk ratio: 5.8; P < 0.005). Extensive nodel dissection appears to prevent recurrence and to improve the cancer-specific survival in EGC patients with nodal metastasis. PMID- 8519671 TI - 2',5'-Oligoadenylate synthetase levels in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b do not correlate with clinical response. AB - In clinical trials with interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, the therapeutic benefit is inconclusive. Although the mechanism(s) by which IFN-alpha 2b prolongs remission in some patients is unknown, 2',5'-oligoadenylate synthetase (2,5-A synthetase) has been used as an objective indicator that IFN-alpha 2b is active in vivo. The enzyme was assayed in cytosol preparations of peripheral blood mononuclear cells (MNCs) from 111 patients who were receiving IFN-alpha 2b and 54 patients who were not, using an assay which measures the conversion of [alpha-32P]ATP to triphospho(adenylyl 2',5')adenosine. 2,5-A synthetase activity was compared with response to intensive therapy and with duration of maintenance therapy. Seventy-three per cent of patients had measurable amounts of 2,5-A synthetase during the first 6 months of maintenance therapy. This percentage decreased with longer follow-up but not significantly. There was no difference between the magnitude of enzyme induction amongst patients who were in complete remission, partial response or who had no change in disease status following intensive therapy. Peripheral blood T cells were a major source of 2,5-A synthetase activity in patients receiving the cytokine. However, both T and B cells produced the enzyme following exposure to IFN-alpha in vitro. The data show that the level of 2,5-A synthetase in patients with multiple myeloma is not indicative of clinical response to IFN alpha 2b. PMID- 8519672 TI - Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study. AB - Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur. PMID- 8519673 TI - Serum tumour markers in carcinoma of the uterine cervix and outcome following radiotherapy. AB - A study was made of the prognostic value of measurements of pretreatment serum marker levels in patients with carcinoma of the uterine cervix undergoing radiotherapy. The markers studied were carcinoma antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). The levels of all three markers increased with disease stage. In a univariate analysis stratifying patients according to either median values or cut-off levels representing the top of the normal range, pretreatment levels predicted patient survival (follow-up times 1-4 years). In a multivariate analysis, disease stage was the most important prognostic variable and, after allowing for stage, only CA125 was a significant independent predictor of treatment outcome. These data suggest that, in carcinoma of the cervix treated with radiotherapy, pretreatment measurements of CA125, but not SCC and TPA, may have a role to play in defining prognosis. PMID- 8519674 TI - High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study. AB - Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia. PMID- 8519675 TI - Phase I study of high-dose epirubicin and vinorelbine in previously untreated non small-cell lung cancer stage IIIB-IV. AB - The aim of the study was to determine the maximum tolerated dose (MTD) for the combination of high-dose epirubicin and vinorelbine in chemotherapy-naive patients with inoperable non-small-cell lung cancer (NSCLC). Twenty-one patients with stage IIIB and IV NSCLC were treated in a single-centre study with escalating doses of epirubicin and vinorelbine given on an outpatient basis. The first dose level comprised epirubicin 100 mg m-2 on day 1 and vinorelbine 20 mg m 2 (days 1 and 8) given intravenously every 3 weeks. Escalating doses for epirubicin and vinorelbine were respectively 120 (day 1) and 20 (days 1 and 8), 120 (day 1) and 25 (days 1 and 8) and 135 (day 1) and 25 (days 1 and 8) mg m-2. Inclusion criteria were age < or = 75 years, ECOG performance score < or = 2 and normal renal, hepatic and bone marrow functions. Dose-limiting toxicities were thrombocytopenia grade II and neutropenia grade III on day 8, febrile neutropenia, and neutropenia lasting > 7 days. No dose-limiting toxicity (DLT) was observed at the first dose level; at the 135/25 mg m-2 dose level three out of six patients had a DLT which was considered as unacceptable. The only non haematological toxicity reaching grade III was nausea/vomiting. One patient showed cardiac toxicity. No neurotoxicity and no treatment-related deaths were seen. The maximum tolerated dose of epirubicin and vinorelbine is 135 mg m-2 (day 1) and 25 mg m-2 (days 1 and 8) respectively, causing mainly haematological toxicity. The recommended dose of epirubicin and vinorelbine for phase II studies is found to be 120 mg m-2 and 20 mg m-2 respectively. PMID- 8519676 TI - Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study. AB - Amifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m-2 i.v. infusion), 21 patients were randomised to receive three cycles of carboplatin alone (C arm) or three infusions of amifostine at 910 mg m-2 (CA arm) at 28 day intervals. The amifostine was given 20 min before and at 2 and 4 h after carboplatin. Since the 910 mg m-2 amifostine infusion led to hypotension in six patients, the dosage was reduced by 25%, to 683 mg m-2 t.i.d., in the other four patients. Amifostine was well tolerated at this dose level. Five patients in the CA arm and three in the C arm had their planned treatment discontinued owing to progressive disease (n = 3), amifostine side-effects (hypotension, sneezing and sickness, n = 4), and carboplatin-induced thrombocytopenia (n = 1). Bone marrow and renal function at study entry and after the first course of carboplatin before randomisation were similar in both treatment arms. Twenty courses of carboplatin+amifostine have been compared with 25 courses of carboplatin alone. Although there was no statistically significant difference with respect to haematological values comparing both arms, the median time to platelet recovery (> 100 x 10(9) l-1) (13.5 days vs 21 days; P = 0.04) and the need for hospitalisation for i.v. antibiotic and other supportive treatment tended to be reduced in the CA arm (0/20 vs 6/25 patient courses; P = 0.06). Response rates and median survival (14 vs 9 months) were no different, excluding tumour protection activity by amifostine. These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation. PMID- 8519677 TI - Smoking and biliary tract cancers in a cohort of US veterans. AB - Except for gallstones, the risk factors for cancers of the biliary tract (CBTs) are poorly understood. Recent case-control studies have suggested cigarette smoking as a potential risk factor. In a cohort study of nearly 250,000 US veterans whose mortality was followed for up to 26 years, we evaluated the risk of CBT associated with tobacco use. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 303 CBT deaths were observed during the follow-up period. Compared with those who had never used any tobacco, current cigarette smokers at entry to the cohort had a 50% excess risk of CBT (RR = 1.5, CI = 1.1-2.0). A nearly 2-fold risk was observed among those who smoked more than 20 cigarettes per day and among those who started smoking under age 20. Non-significant increases in risk occurred among smokers of other forms of tobacco. This cohort study is consistent with reports that smoking is a risk factor for CBT, but further studies are needed to clarify whether the effect is specific for certain subsites and whether it reflects an association with pre existent gallstones. PMID- 8519678 TI - The epidemiology of non-seminomatous germ cell tumours in the west of Scotland 1975-89. AB - A total of 438 males resident in the six West of Scotland Health Board areas were notified to the cancer registry with a diagnosis of teratoma between 1 January 1975 and 31 December 1989. Non-registration was between 2% and 3.4%; a further 44 cases were ascertained through independent listings in the major tertiary referral centres. There were four (1%) duplicate registrations and 16 (4%) were incorrect on the basis of pathology (three) or residence (13). Of these, most (26) were registered with alternative diagnoses and eight were registered on the pre-1985 manual system. The positive correlation between socioeconomic status and incidence was confirmed by linking residential postcode at diagnosis to the Carstairs and Morris Deprivation Index. There was an increasing incidence, both overall and for men aged 15-44 years, with doubling times of 20 and 25 years respectively. The increase was confined to men resident in the more deprived postcode sectors; the incidence rate among men from the most affluent areas remained unchanged throughout the period of study. PMID- 8519679 TI - Cancer and congenital abnormalities in Asian children: a population-based study from the West Midlands. AB - Cancer and associated congenital abnormalities were investigated in Muslim and non-Muslim Asian children from the West Midlands. Cancer incidence rates were calculated for Indian (non-Muslim), Pakistani/Bangladeshi (Muslim) and white children diagnosed from 1978 to 1992. Incidence was significantly higher in the Pakistanis, with an age-standardised rate (ASR) of 163 cases per million per year, compared with 115 for Indian and 125 for white children. Among Asian cancer patients, congenital malformations were significantly more common in Muslim (21%) compared with non-Muslim (7%). In Muslims the malformation excess was caused by autosomal recessive and dominant disorders (in 8% and 5% of cases respectively). Cancer malformation/predisposition syndromes were found in 10% of Muslims, compared with 2% of non-Muslims. In 33% of the Muslims with malformations, childhood cancer and a malformation were also present in a close relative. None of the non-Muslims with malformations had a relative with childhood cancer. The cancer excess in Muslims may be partly related to inherited genes causing both malformations and cancer. The prevalence of autosomal recessive disorders may be related to consanguinity, which is common in the Pakistani Muslim population. The high incidence of autosomal dominant disorders may be related to older paternal age at conception, giving rise to spontaneous mutations. PMID- 8519680 TI - Transfected cathepsin D stimulates high density cancer cell growth by inactivating secreted growth inhibitors. AB - Cathepsin D, a lysosomal protease, is overexpressed in primary breast cancer and associated with increased risk of metastasis. We have shown previously by transfection in rat tumor cells that overexpression of cathepsin D increased both experimental metastasis in nude mice and in vitro proliferation under low-serum conditions. In this study, we used the transfected cell lines to investigate the mechanism by which cathepsin D prevents density-dependent arrest of cell proliferation. This effect was not associated with a general alteration of cell substratum or cell-cell adhesiveness. As shown by coculture and conditioned media experiments, control cells reaching saturation density released inhibitory activity that was able to prevent the growth of control or cathepsin D transfectants and decreased the cloning efficiency of normal rat kidney fibroblasts in agar. By contrast, in media from two cathepsin D-transfected cell lines, this inhibitory activity was markedly reduced. Cathepsin D overexpression did not affect cell sensitivity to the inhibitor but modified the secretion of several proteins. The increase in cell density appeared to be due to intracellular maturation of cathepsin D since it was reversed by amine treatment that neutralizes the pH of acidic compartments within the cells. Moreover, the addition of secreted pro-cathepsin D was unable to increase the saturation density of control clones. Finally, the inhibitory factor was partially characterized as a heat-labile, secreted protein. We conclude that cathepsin D overexpression increases the growth of cancer cells to a higher density via an intracellular mechanism, leading to a decreased secretion of growth inhibitor(s). PMID- 8519681 TI - Misregulated expression of the cyclin dependent kinase 2 protein in human fibroblasts is accompanied by the inability to maintain a G2 arrest following DNA damage. AB - The misregulation of cell cycle checkpoints has been implicated in the onset of neoplasia. To thoroughly understand the differences in checkpoint regulation between normal and transformed cells, we have compared the cell cycle responses of normal and TAg-transformed fibroblasts to DNA damage by gamma-irradiation. Normal cell lines arrest in both G1 and G2 for in excess of 48 h after DNA damage. Surprisingly, both cyclin-dependent kinase 2 (CDK2) and cyclin A proteins were specifically down-regulated within 24 h of DNA damage. In contrast, TAg transformed cells did not down-regulate either cyclin A or CDK2 after DNA damage and showed a significantly shortened G2 arrest. To investigate the role CDK2 down regulation plays in cell cycle arrests, we generated normal cell lines that constitutively overexpress CDK2. These cells fail to down-regulate both CDK2 protein and CDK2 protein kinase activity after DNA damage and also show a G2 checkpoint defect; although the cells are able to normally initiate both a G1 and a G2 arrest, they prematurely escape the G2-M arrest after DNA damage. The escape from G2 correlates with an illicit activation of cyclin B-associated protein kinase activity in these cells. These results suggest that the misregulation of CDK2 contributes to the failure of checkpoint control by allowing cells to enter mitosis prematurely. PMID- 8519682 TI - G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase). AB - CaMK-II (the type II multifunctional Ca2+/calmodulin kinase) is a ubiquitous serine/threonine protein kinase that is activated by Ca2+ and calmodulin (CaM) and has been implicated in cell cycle control. NIH 3T3 fibroblast cytosolic extracts contain CaMK-II enzymatic activity and two major Ca2+/CaM-dependent phosphoproteins of M(r) 55,000 and 115,000. Reverse transcription-PCR indicates that the gamma B and gamma C isozymes of CaMK-II are predominately expressed. KN 93, a novel membrane-permeant synthetic inhibitor of purified neuronal CaMK-II, inhibits serum-induced fibroblast cell growth in a comparable dose-dependent fashion to its inhibition of CaMK-II activity. After 2 days of KN-93 treatment, 95% of cells are arrested in G1. G1 arrest is reversible; 1 day after KN-93 release, a peak of cells had progressed into S and G2-M. KN-92, a similar but inactive compound, had no effect on CaMK-II activity or cell growth. KN-93 also blocked cell growth stimulated by basic fibroblast growth factor, platelet derived growth factor-BB, epidermal growth factor, and insulin-like growth factor 1. After 3 days of KN-93-induced G1 arrest, cell size and viability decreased and DNA fragmented, indicating apoptosis. These data suggest that CaMK-II is necessary for cell cycle progression through G1 and operates at a site common to the transduction of signals from growth and/or survival factors. PMID- 8519683 TI - bcl-2 inhibits wild-type p53-triggered apoptosis but not G1 cell cycle arrest and transactivation of WAF1 and bax. AB - We have earlier shown that wild-type (wt) p53 expressed from a temperature sensitive construct (ts p53) triggers apoptosis in the v-myc retrovirus-induced, p53-negative T-cell lymphoma line J3D (Y. Wang et al., Cell Growth & Differ., 4: 467-473, 1993). We also found that constitutive bcl-2 expression inhibits wt p53 triggered apoptosis in these cells (Y. Wang et al., Oncogene, 8: 3427-3431, 1993). Here we demonstrate that more than 90% of the ts p53-transfected J3D cells were arrested in G1 at 18 h after induction of wt p53 expression by temperature shift to 32 degrees C. At this time, at least 80% of the cells remained viable. After 30 h at 32 degrees C, around 50% of the cells had died by apoptosis, while most of the remaining cells were still alive in G1, indicating that p53-induced apoptosis occurred following G1 arrest. The G1 cell cycle arrest at 18 h after temperature shift to 32 degrees C was reversible, as shown by the fact that the cells readily resumed exponential growth following temperature shift back to 37 degrees C, although viability dropped from around 80 to 65%. Expression of both WAF1 and bax mRNA was induced by wt p53 in both the ts p53 and ts p53/bcl-2 transfected cells. The kinetics of G1 cell cycle arrest at 32 degrees C was similar in both the ts p53 and the ts p53/bcl-2 double transfectants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519684 TI - Expression of retinoic acid receptor beta mediates retinoic acid-induced growth arrest and apoptosis in breast cancer cells. AB - The expression of the retinoic acid receptor beta (RAR beta) mRNA is absent or down-regulated in most human breast cancer cell lines. To investigate the role RAR beta may have in regulating the proliferation of breast cancer cells, we used retroviral vector-mediated gene transduction to introduce the human RAR beta gene into two RAR beta-negative breast tumor cell lines, MCF-7 and MDA-MB-231. RAR beta-transduced clones underwent growth inhibition associated with G1 arrest when treated with 1 microM all-trans-retinoic acid (RA). Moreover, the MCF7-RAR beta transduced clones also underwent apoptosis after 4 to 6 days of RA treatment. The RA-induced growth arrest in MDA231-RAR beta transduced cells is associated with c myc mRNA down-regulation, whereas the RA-mediated apoptosis of MCF7-RAR beta transduced cells is not associated with c-myc down-regulation. These observations suggest a critical role for RAR beta in mediating growth arrest and apoptosis in breast cancer cells. PMID- 8519686 TI - Regulation of ornithine decarboxylase mRNA levels in human breast cancer cells: pattern of expression and involvement of core enhancer promoter element. AB - Ornithine decarboxylase (ODC) expression is increased by growth factors and is obligatory for progression through the cell cycle in a wide variety of cell types. In this study, a variant human ODC cDNA was identified, sequenced, and used to probe mRNA levels in human breast tumor cell lines and xenografts. ODC mRNA was elevated about 3-fold in estrogen receptor-negative (ER-) tumors (MDA-MB 231) when compared with ER-positive (ER+) tumors (MCF-7), as assessed by quantitative autoradiographic analysis of in situ hybridization experiments. The pattern of ODC mRNA in MDA-MB-231 (ER-) xenografts was polarized to the extreme periphery of the tumor, whereas the distribution of ODC mRNA was more evenly distributed in MCF-7 (ER+) xenografts. This correlates with hematoxylin and eosin staining patterns, suggesting that ER+ and ER- xenografts have a differential dependence on host vasculature for growth factor supply. ODC mRNA was elevated 5 fold in MDA-MB-231 cells versus MCF-7 cells when analyzed in cell culture. These relative mRNA levels correlate with increased levels of "core" enhancer binding nuclear proteins in MDA-MB-231 cells over that detected in MCF-7 cells. PMID- 8519685 TI - Induction of cell death in murine fibroblasts by a c-myc promoter binding protein. AB - The c-myc promoter binding protein (MBP-1) was identified previously from a human cervical carcinoma cell (HeLa) cDNA expression library (R. Ray and D. M. Miller, Mol. Cell. Biol., 11: 2154-2161, 1991). This study demonstrated that MBP-1 binds to the mouse c-myc P2 TATA box sequences and exerts a negative regulatory role on c-myc transcription. The role of MBP-1 on cell growth was initially examined by transfection of fibroblast cells with MBP-1 cDNA and resulted in rapid cell death. Subsequently, MBP-1 cDNA bearing an inducible promoter was introduced in murine fibroblast cells (NIH3T3) to control the expression of the exogenous MBP 1. Upon induction of exogenous MBP-1 expression, stable transfectants showed reduced c-myc expression, cell death, and DNA fragmentation. To further analyze whether c-myc inhibition mediates or complements the effect of MBP-1, the exogenous MBP-1 when introduced into NIH3T3 cells expressing deregulated human c myc gene, cell death was interrupted. This study suggested that exogenous expression of MBP-1 induces cell death in fibroblasts by blocking cell proliferation. PMID- 8519687 TI - Multiple elements in the 5' untranslated region down-regulate c-sis messenger RNA translation. AB - Expression of the platelet derived growth factor (PDGF) B-chain, the product of the c-sis proto-oncogene, is regulated both at the transcriptional and translational level. Previous studies have shown that the long 5' untranslated region (UTR) of the c-sis mRNA strongly inhibits synthesis of the PDGF-B chain. However, the assignments of down-regulatory regions within the 5' UTR were ambiguous. Expression of several site-directed point and deletion mutants of the 5' UTR of the c-sis mRNA in COS1 cells revealed that the UTR inhibited PDGF-B chain synthesis in a more complex manner than indicated by the previous studies. Abrogation of the three upstream short open reading frames by mutating each of the AUGs did not have any effect on the synthesis of the PDGF-B chain. Expression of deletion mutants revealed two partially overlapping regions, nucleotides 1-651 and 475-1022, each of which independently inhibited c-sis mRNA translation as effectively as the entire 5' UTR. Each of these regions contains a potentially strong stem-loop structure and a GC-rich element. These elements of the alternate down-regulatory regions could interact within the same region and/or with the elements of the other regulatory region to block c-sis mRNA translation. We show, in contrast to the previous reports, that the inhibition of c-sis mRNA translation cannot be attributed exclusively to any particular predicted secondary structure or a GC-rich element within the 5' UTR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519688 TI - Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells. AB - Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (LS174T and LS1034) and of SCF in 9 of 11 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS174T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of LS174T in a dose dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. LS174T cells expressed the M(r) 145,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of LS174T by 40%. Interleukin 4 (IL-4) completely inhibited SCF-induced proliferation of LS174T cells. Interestingly, IL-4 induced an almost complete down-regulation of both c-kit and SCF expression in LS174T. Our findings suggest that in LS174T cells, an SCF-mediated autocrine loop is functional and that IL-4 down-regulates the expression of both the receptor and the ligand of this circuit. PMID- 8519689 TI - Activation of the mitogen-activated protein kinase cascade in response to the temperature inducible expression of v-mos kinase. AB - We have characterized activation of the MAP kinase cascade in an inducible system in response to the temperature-sensitive (ts) expression of the v-mos oncogene. Transformation of immortalized rat embryo fibroblasts by a ts isolate of Moloney murine sarcoma virus (Mo-MuSVts110) constitutively activates MAP kinases (ERK-1 and ERK-2) and MAP kinase kinases (MKK-1 and MKK-2) only at the permissive temperature when v-mos kinase is present and active. Following a shift of the ts transformed, serum-starved cells from the nonpermissive to permissive temperature, MAP kinases and both MKK-1 and MKK-2 are activated within 1-2 h, concurrent with the reappearance of active mos kinase. Raf-1 kinase activity increases more slowly in response to the reappearance of v-mos, and the mobility shift indicative of hyperphosphorylation was only detected 18 h after the temperature transition. Our data show that MAP kinase cascade activation is an early event following the reappearance of v-mos expression and v-mos kinase activity upon temperature shift, while the first manifestation of morphological transformation appears 24 h after the shift to permissive temperature. These results support the hypothesis that mos acts through the MKK to induce cell transformation. PMID- 8519690 TI - Protein kinase C-dependent and -independent pathways of signal transduction in prostate cancer cells: fibroblast growth factor utilization of a protein kinase C independent pathway. AB - To examine the possibility that differences in protein tyrosine phosphorylation contributed to differences in fibroblast growth factor (FGF) responsiveness of clonally derived C3 (modestly responsive) and T5 (highly responsive) rat prostate cancer cells, we evaluated the ability of orthovanadate to affect prostate cancer cell thymidine incorporation. These analyses showed that C3 cell FGF insensitivity was not attributable to enhanced protein phosphotyrosine phosphatase activity. Analyses of acidic FGF (aFGF)-mediated protein phosphorylation showed mitogen-caused, time-dependent tyrosine phosphorylation of C3 and T5 cell FGF receptors (FGFRs) and other proteins having a mass of 190, 150, 120, 100, 90, 80, 74, 60/62, 50, 42, or 28 kilodaltons. Although marked differences characterized aFGF mediated intensity of tyrosine phosphorylation, the notable commonality of tyrosine phosphorylation and the mass of the phosphorylated proteins suggested that C3 and T5 cells may use the ras and/or protein kinase C (PKC) pathways for FGF-mediated signal transduction. The PKC agonist 12-O-tetradecanoyl-phorbol-13-acetate (TPA) caused concentration dependent increases in T5 cell thymidine incorporation. In contrast, TPA did not enhance thymidine incorporation of C3 cells or mitogen-sensitive NRK cells included as a nonneoplastic control. TPA also significantly enhanced T5 cell proliferation, whereas identical treatment did not affect proliferation of either C3 or NRK cells. Either 12 or 24 h treatment with 200 or 2000 ng/ml TPA caused complete PKC alpha and partial PKC delta down-regulation in C3, T5, and NRK cells. Consequently, the failure of TPA to affect C3 or NRK cell thymidine incorporation or proliferation was not attributable to potential TPA ineffectiveness in these cells. Survey immunological analyses showed that all three cell lines lacked PKC beta, PKC eta, and PKC theta. In contrast, T5 cells contained abundant amounts of PKC epsilon, whereas the PKC epsilon content of C3 and NRK cells was near the limit of detection. TPA treatment of T5 cells evoked only partial PKC epsilon down-regulation. Both aFGF and basic FGF (bFGF) promoted concentration-dependent enhancement of TPA-pretreated T5 cell thymidine incorporation, and the effects of combined TPA and either aFGF or bFGF treatment were additive. Neither aFGF nor bFGF was able to enhance thymidine incorporation of TPA-pretreated C3 cells beyond the modest effects elicited by FGF treatment of C3 controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519691 TI - A diphtheria toxin/fibroblast growth factor 6 mitotoxin selectively kills fibroblast growth factor receptor-expressing cell lines. AB - The fibroblast growth factors (FGFs) constitute a family of nine polypeptides implicated in a number of physiological and pathological processes. They bind to at least three types of cell surface molecules, including low and high affinity receptor families. The role of FGFs and their receptors in human tumorigenesis has been suspected but not formally proven. FGF6 is an oncogene encoding a precursor protein of 208 amino acids that has been shown to bind to FGF receptors. Its normal function has not been identified, but its restricted pattern of expression suggests a role in muscle development or function. We have constructed, produced, and purified a diphtheria toxin/FGF6 mitotoxin that selectively kills FGF receptor-expressing cells. Interestingly, at least two cell lines that normally respond to FGF6 have been found resistant to DT/FGF6, suggesting that FGF6 acts on these cells through a transduction pathway that does not involve FGF receptor. PMID- 8519692 TI - Resistance to transforming growth factor beta and activin due to reduced receptor expression in human breast tumor cell lines. AB - Loss of sensitivity to growth inhibition by transforming growth factor (TGF)-beta is a phenomenon often observed in human epithelial tumor cells and is linked to malignant progression. We tested a panel of estrogen receptor (ER)-positive and negative breast cell lines for their sensitivity to TGF-beta and a related member of the TGF-beta superfamily, activin. Both TGF-beta-sensitive (MCF7, Hs578T, and BT20) and -resistant (two T47D variants, ZR75-1, MDA-MB231, and MDA-MB468) cell lines were found, with no strict correlation between ER content and sensitivity to TGF-beta. In contrast, all four ER-positive cell lines were inhibited by activin A, whereas the ER-negative lines were not. To examine whether resistance to TGF-beta and activin resulted from the absence of the corresponding receptors, mRNA expression of the types I and II receptors was studied. TGF-beta receptor II was not expressed in the two T47D variants and was low in ZR75-1 cells. Upon stable transfection of the TGF-beta receptor II in one of the T47D variants, sensitivity to TGF-beta 1 and TGF-beta 2 was restored with respect to inhibition of anchorage-dependent and -independent proliferation, indicating that other signal transduction components are functionally intact. Sensitivity to TGF-beta in the transfectants was dependent on the expression level of the newly introduced receptor. Resistance to activin in the ER-negative cell lines could be explained in BT20 and Hs578T cells, but not in MDA-MB231 and MDA-MB468, by low activin receptor expression. These results show that resistance to TGF-beta and activin is often, but not always, due to reduced expression of the signaling receptor in breast cancer cells. The activin resistance of ER-negative breast tumor cells may be involved in their increased malignancy compared with ER positive cells. PMID- 8519693 TI - Inhibition of gamma-glutamyl transpeptidase activity at the surface of human myeloid cells is correlated with macrophage maturation and transforming growth factor beta production. AB - The protease gamma-glutamyl transpeptidase (gamma-GT) activity was detected at the surface of human blood granulocytes and monocytes and myeloblastic HL-60 and monoblastic U937 leukemia cell lines using an enzymatic assay (cleavage of gamma glu-p-nitroanilide and inhibition by the specific irreversible inhibitor of gamma GT, i.e., acivicin). Flow cytometric analysis of gamma-GT expression and detection of a 2.4-kb gamma-GT mRNA species by Northern blot analysis confirmed the presence of gamma-GT in cells of the monocytic-granulocytic lineage. Differentiation of HL-60, U937 cells, and blood monocytes along the macrophage pathway or granulocytic maturation of HL-60 cells was accompanied by an increase in gamma-GT mRNA levels without modulation of cell surface gamma-GT activity and protein. When added to leukemic cell cultures, acivicin produced a dose- and time dependent inhibitory growth effect associated with the induction of morphological features characteristic of macrophage maturation and enhanced surface expression of phenotypic markers CD11b and CD71 characteristic of monocyte development. When cultured in the presence of acivicin, freshly isolated monocytes also underwent characteristic changes in morphology and antigenic phenotype (increase in CD71 and HLA-DR class II) consistent with their differentiation into macrophages. In parallel, a marked production of latent transforming growth factor (TGF)-beta was observed in supernatants of cells cultured with acivicin, although TGF-beta 1 mRNA species were expressed in these cells at a level almost similar to that in unstimulated cell cultures. Moreover, acivicin-treated cells still differentiated into macrophages in the presence of a neutralizing antibody to TGF-beta 1/beta 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519694 TI - Inhibitors of the intracellular Ca(2+)-ATPase in cultured mouse keratinocytes reveal components of terminal differentiation that are regulated by distinct intracellular Ca2+ compartments. AB - Differentiation of mammalian epidermis is associated with spatially and temporally coordinated changes in gene expression as cells migrate from the proliferative basal cell compartment through the nonproliferative spinous and granular cell layers where the terminal phase of maturation is completed. Previous studies have suggested that a gradient of Ca2+ in the epidermis in vivo and increased extracellular Ca2+ in vitro induce differentiation of mammalian epidermal keratinocytes. Chelation of intracellular free Ca2+ prevents this Ca(2+)-induced differentiation, but sites of action for intracellular Ca2+ remain undefined. In this study, thapsigargin (Tg) and cyclopiazonic acid (CPA), inhibitors of the endoplasmic reticulum Ca(2+)-ATPase, were used to evaluate the relative contribution of cytoplasmic and stored Ca2+ to Ca(2+)-induced terminal differentiation of cultured mouse keratinocytes. A sustained increase of both intracellular free Ca2+ (Cai) and ionomycin-sensitive Ca2+ stores is associated with Ca(2+)-induced keratinocyte terminal differentiation. Tg and CPA was used to change this coordinated regulation of free and stored Ca2+. In the absence of extracellular Ca2+, both Tg and CPA transiently increase Cai and deplete intracellular Ca2+ stores; while in the presence of extracellular Ca2+, Tg and CPA stimulate Ca2+ influx and cause a sustained increase in Cai while depleting stored Ca2+. In the presence of extracellular Ca2+, Tg (5 to 20 nM) and CPA (5 to 25 microM) inhibit Ca(2+)-induced morphological changes and stratification and prevent the suppression of DNA synthesis by Ca2+. Tg and CPA also inhibit the expression of mRNA and protein for specific epidermal spinous cell markers, keratins 1 (K1) and 10 (K10), prevent the redistribution of E-cadherin from a diffuse membranous pattern to concentration at cell-cell junctions, and inhibit the activation of a reporter gene regulated by a K1 enhancer element shown previously to be Ca2+ sensitive. These effects of Tg and CPA can be reversed by increasing the extracellular Ca2+ to levels that partially restore Ca2+ stores. In contrast, Tg and CPA enhance the expression of profilaggrin and loricrin mRNA and protein, markers of granular cell differentiation. These divergent actions of Tg and CPA on distinct components of the keratinocyte differentiation program suggest that adequate intracellular Ca2+ stores are important for the expression of spinous cell proteins and inhibition of DNA synthesis, while elevation of Cai stimulates the expression of markers of granular cell differentiation. PMID- 8519695 TI - Identification of tuberous sclerosis 2 messenger RNA splice variants that are conserved and differentially expressed in rat and human tissues. AB - Tuberous sclerosis 2 (Tsc2) gene is the target of a germline insertion in the Eker rat model of inherited cancer susceptibility. This tumor suppressor gene, when mutated, gives rise to a spectrum of epithelial and nonepithelial neoplasms in the rat, as well as multisystem involvement of hamartomas in the human. In this study, we characterized the rat Tsc2 cDNA and found that it is highly homologous with the human gene, including a conserved rap1GAP catalytic domain. Sequence analysis of independent rat clones from a kidney cDNA library revealed distinct but related variants of the Tsc2 transcripts stemming from alternative splicing involving two noncontiguous exons within the translated region. The first of these, located at amino acids 947 to 990, gives rise to isoforms with or without the 129-bp exon. There exists another variant related to the use of a "cryptic" splice acceptor site in the downstream exon that results in an in-frame 3-bp deletion. A separate 69-bp exon encoding a novel serine-rich amino acid sequence (1272 to 1295) was also alternatively spliced. Together, we have found a minimum of four and potentially eight Tsc2 isoforms that are differentially expressed in a tissue-specific manner. These splice variants are highly conserved in the human gene, suggesting a possible functional role of these Tsc2 isoforms in various cell regulatory and developmental processes. PMID- 8519696 TI - The BTB/POZ domain: a new protein-protein interaction motif common to DNA- and actin-binding proteins. AB - The BTB/POZ domain defines a newly characterized protein-protein interaction interface. It is highly conserved throughout metazoan evolution and generally found at the NH2 terminus of either actin-binding or, more commonly, nuclear DNA binding proteins. By mediating protein binding in large aggregates, the BTB/POZ domain serves to organize higher order macromolecular complexes involved in ring canal formation or chromatin folding. PMID- 8519697 TI - Open clinical trial of roxithromycin amongst patients of Jos University Teaching Hospital with lower and upper respiratory tract infections. AB - An open non-comparative clinical study to determine the efficacy and tolerance of Roxithromycin 150 mg twice daily was carried out amongst Nigerian patients with acute upper and lower respiratory tract infections. Twenty-four (24) patients (mean age 21.6 years, male 13; females 11 who completed the study presented with acute tonsillitis (33.3%, acute bronchitis (12.5%), lober pneumonia (12.5%), Otitis media (8%), acute pharyngitis (4%) and acute sinusitis (4%). Most of the patients had normal bacterial flora isolated (50.3%). Pathogens isolated included streptococcus pyogenes (21%), moraxella catarhalis (8.3%), streptococcus pneumonia (8.3%) and Klebsiella pneumonia (4%). The quick clinical response, lack of major adverse drug reactions and susceptibility of the bacterial isolates to Roxithromycin were very significant attributes of the drug. In addition, there was complete recovery in 95.8% of the patients. Roxithromycin is therefore a well tolerated and effective drug for the treatment of acute respiratory tract infections in Nigerian patients. PMID- 8519698 TI - Socio-cultural influences on eye health in a rural underserved community of Oyo state. AB - To enhance planning of an eye health programme for a rural underserved community, focus group discussions were conducted. They investigated the community perception about eye health, and determined some of the socio-cultural factors which may be important in design of the programme. The results suggest that the planned intervention is timely and appropriate. Eye health education will be required to discourage the use of Traditional Eye Medicines, while the possibility of incorporating Traditional Healers as first contact for patients will need to be examined. Cataract surgery will be a highlight of the programme. PMID- 8519699 TI - Domestic ocular and adnexal injuries in Nigerians. AB - A study of domestic ocular and adnexal injuries over an 18 month period at the Guiness Eye Centre Onitsha showed that they constitute 26.4% of all cases of ocular trauma. Women and children were at a greater risk of sustaining eye injuries from domestic activities. The activities leading to injuries in the 45 patients studied were fight, children's play, chopping firewood, plucking fruits/vegetables and corporal punishment; the injuries were inflicted by self; playmates, siblings, parents and husbands; the agents of injury were fist, missibles, sticks and other sharp objects, exploding bottles and human bite. Most patients presented more than one week after injury. Only 18 patients (40%) kept follow-up appointment. Among these visual acuity improved in 11 while 5 remained blind. The importance of these epidemiologic characteristics in relation to prevention of such injuries and reduction of ocular morbidity in established cases are discussed. PMID- 8519700 TI - Coitally--related morbidities in the non-pregnant female. AB - The consequences of coital experience in the non-pregnant female are varied and are occasional diagnostic puzzles. They range from those typified by manifest or concealed haemorrhage, to those revealed by immunologic, neurologic or pharmacologic phenomena and to those, whose patho-physiology is as yet, unclear. Observations are made of the likelihood of recurrence, and that, most patients would typically not readily admit to the preceding act of coitus. PMID- 8519701 TI - The micro-erythrocyte sedimentation rate as a screening test for bacteraemia in young children with non-focal infections. AB - The micro-erythrocyte sedimentation rate (micro-ESR) was evaluated in 349 patients without focal signs of infection with bacteraemia, bacteraemia/malaria, malaria (218) and fever of undetermined origin(100). There were significant differences between the diagnoses in their mean micro-ESR uncorrected for anaemia (F ratio = 3.66, p = 0.013 for one way analysis of variance). The sensitivity of uncorrected micro-ESR > 20mm/hr for bacteraemia was moderate (53%) and specificity was low (32%); for bacteraemia/malaria sensitivity was high (88%) but specificity was also low (33%). The positive predictive value of micro-ESR > 20mm/hr was low for bacteraemia (3%) and bacteraemia/malaria (6%) whereas the negative predictive value was high for bacteraemia (94%) and very high for bacteraemia/malaria (98%). We conclude that a low micro-ESR (< 20mm/hr) may be helpful in ruling out bacteraemia, especially bacteraemia/malaria, in young febrile children without focal signs. PMID- 8519702 TI - Endometrial dating correlated with multiple luteal progesterone levels in confirming ovulation and luteal function in infertile Nigerian women. AB - Infertility is a medico social problem in Nigeria and it accounts for 40 percent of our outpatient gynaecological consultations; therefore the need to evaluate the two common presumptive methods of ovulation (serum progesterone and endometrial history) is indicated. An endometrial biopsy and three blood samples taken between M-4 and M-11 (4 and 11 days to the next menstruation) for progesterone determination in the luteal phase of the cycles of 50 infertile Nigerian women were analyzed. The methods were compared for confirmation of ovulation and evaluation of luteal functions. Total luteal phase progesterone value of 11.3 nmol/1 or greater was consistent with ovulation (secretory endometrium) in 90% of the cycles. 41 cycles yielded sufficient information to compare the two methods for evaluation of luteal function. The total progesterone value of 15 nmol/1 or greater was consistent with in-phase biopsies. Twenty eight (68.3%) of the cycles showed evidence of In-Phase (IP,) biopsies while thirteen (32.7%) showed out of phase (00P) biopsies suggestive of abnormal luteal function. The mean progesterone levels of patients with IP biopsies were significantly higher than those with 00P biopsies (P < 0.0001). Compared to studies by other workers using single midluteal progesterone assay, it seems multiple progesterone assay does not confer added advantage in confirming ovulation or in evaluation of luteal function. It is suggested that simultaneous measurements of serum progesterone levels with endometrial biopsies should be used to document ovulation and luteal function in infertile Nigerian women in view of the scarcity of ultrasonographic machines and emerging new technologies in our practice. PMID- 8519703 TI - Tobacco and cannabis smoking in secondary school pupils in Bo, Sierra Leone. AB - A questionnaire survey of 713 pupils of Secondary Schools in Bo town, Southern Sierra Leone, on tobacco and cannabis smoking was carried out in January and February 1994. There were 56.8% males and 43.2% females with a mean age of 17.6 +/- 1.5 years. Lifetime use of both substances was 9% while current use was 4.2%. Current use of cigarettes was 3.2% and of cannabis 2.2%. Forty percent of current users smoked both cigarettes and cannabis. The mean age of onset of smoking was 15.1 +/- 3.1 years. Males smoked significantly more than females (p < 0.001). The prevalence of smoking increased with age and from junior to senior forms. There was also a higher prevalence among muslim students. Smoking within the family was a significant determinant of smoking in School children (p < 0.01). Current smokers were less aware of the health hazards of smoking but the majority of previous smokers stopped the habit because they thought it was bad for their health. In spite of these relatively rates, it is recommended that appropriate health education programme on tobacco and cannabis smoking be incorporated into school curricula. Further studies are indicated in more urbanized areas and in colleges. PMID- 8519704 TI - [Coronary veins and coronary sinus tributary veins in Africans]. AB - This anatomical study carried out on 40 African adults hearts studied branches of the coronary sinus. By using of injection of the coronary arteries and corrosion of the myocardium, the study identified certain peculiarities of the small coronary vein and the posterior descending interventricular vein in Africans. PMID- 8519705 TI - The aortic width as an index of hypertension--how specific? AB - Primary aortic diseases are believed to be rare in our environment, the result of which is to attribute increase in aortic width to hypertension. This premise has advised certain widely held views in the past, one of which is that heart muscle diseases (dilated cardiomyopathy) is hypertensive heart disease in disguise. New trends in knowledge have led to a shift in ground. Dilated cardiomyopathy is now thought to be an end-stage situation with many factors operating. This has prompted this re-look at the main factor that advised the earlier stand, namely the aortic width on chest X-ray. 48 patients in hypertensive heart failure and 50 in heart failure from dilated cardiomyopathy were studied. Aortic root dimensions were measured on chest X-ray and echocardiography. The results point to the fact that in our adult population, aortic dimension is a poor specific index of hypertension, as there was no statistically significant difference between the groups. PMID- 8519706 TI - Anaesthesia in The Gambia. AB - We review the development of anaesthesia in The Gambia from 1977 to 1992 and the role of nurse anaesthetists. The anaesthetists service provided over a one year period at the Royal Victoria Hospital, Banjul shows that 58.3% are for Obstetrics and Gynaecology (O & G) procedures, 38.06% for Surgical and Dental while 3.164% was Ophthalmology. Nurse anaesthetists administered anaesthesia for 94.4% of the O & G Procedures with minimal complication. However anaesthesia for 65.6% of the general surgical and dental procedures required the expertise of a physician anaesthetist. The major problems associated with anaesthetic service delivery in The Gambia are highlighted and suggestions made on the future development of the specialty of anaesthesia. PMID- 8519707 TI - Morphological patterns of paediatric solid cancer in Lagos, Nigeria. AB - With successful implementation of the Expanded Programme on Immunisation (E.P.I.), many Nigerian children are protected against the common infections of childhood which claim their lives within the first decade of existence. Recent observations tend to show that paediatric cancer may start to play a significant role in childhood morbidity and mortality. Therefore, this study analyses 372 cases of paediatric solid malignant tumours received at the Department of Morbid Anatomy, Lagos University Teaching Hospital (L.U.T.H) from 1974 to 1988. Considering all the age groups together, the commonest malignant tumour is lymphoma (32.8%), of which Burkitt's lymphoma accounts for 19.6%. Retinoblastoma and Wilms' tumour represent second and third commonest solid cancers respectively. There is, however, slight variation in the different age groups. For example, in the age group 1-4 years, malignant lymphoma is an uncommon disease representing only 11.0% of all cancers whilst retinoblastoma (34.5%) and nephroblastoma (24.0%) together account for 58.6%. Epithelial cancer although rare in children, represents 12.6% in the 10-14 year age group. There is a higher incidence of this tumour when compared to the other age groups (less than 1 year, 1-4 years and 5-9 years). Intracranial neoplasia are uncommon, representing only 2.0%. The overall incidence of solid malignant tumours in children aged 0-14 years in Lagos is estimated to be 22 per million person years. PMID- 8519708 TI - [Vascularization of the sinus node in the Black African]. AB - The aim of this study is to identify in 43 adults african hearts the different arteries of the sinus node. The method used is the injection corrosion technique of the coronary vessels. The study concludes that the right coronary system is the principal way of irrigation of sinus node in Africans (46.6% of cases). PMID- 8519709 TI - Isolated internal iliac artery aneurysm and urinary retention. AB - A 74 year old patient presented with retention of urine as a result of an isolated right internal iliac artery aneurysm. The diagnostic difficulty leading to a delayed diagnosis resulted in rupture of the aneurysm. An endoaneurysmorrhaphy of the internal iliac artery was performed and the right common and external iliac arteries were anastomosed end to end. An early diagnosis and prompt therapy is recommended for this rare lesion. PMID- 8519710 TI - Penetrating maxillofacial trauma--a case report. AB - An unusual presentation of a penetrating maxillofacial injury in which a piece of wood penetrated oro-facial and upper neck tissues is reported. Similar reports in the literature were briefly reviewed and principles of management highlighted. PMID- 8519711 TI - Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine. AB - BACKGROUND AND OBJECTIVES: In addition to major neurologic injury, local anesthesia toxicity may also include less severe but more common neurologic side effects. The authors recently observed symptoms suggestive of transient radicular irritation in one third of patients after spinal anesthesia with hyperbaric 5% lidocaine, whereas evidence of neurologic symptoms was lacking with hyperbaric 0.5% bupivacaine. The purpose of this prospective double-blinded study was to evaluate if the high osmolarity of hyperbaric 5% lidocaine solution might contribute to the development of transient radicular irritation. METHODS: Forty four patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1.5 mL of one of three study drugs: 5% lidocaine in 7.5% dextrose (drug A), 0.5% bupivacaine in 8.25% dextrose (drug B), or 5% lidocaine in 2.7% dextrose (drug C). Drug C was prepared by the pharmacy (University Hospital, Basel, Switzerland) with an osmolarity similar to that of drug B. Drugs A and B were commercially available. Patients were evaluated on postoperative day 1 for symptoms of transient radicular irritation by an anesthesiologist who was unaware of the drug given or details of the anesthetic technique. RESULTS: Symptoms suggestive of transient radicular irritation were observed with a similar high incidence in patients receiving both lidocaine preparations, but in no patient receiving hyperbaric 0.5% bupivacaine (P < .01). CONCLUSIONS: The results suggest that transient radicular irritation did not result from the marked hyperosmolarity of the hyperbaric 5% lidocaine. However, because lidocaine and bupivacaine were not administered at equipotent dosages, the relative potential for both drugs to induce transient radicular irritation remains to be determined. PMID- 8519712 TI - Alkalinization of local anesthetics. Which block, which local anesthetic? AB - BACKGROUND AND OBJECTIVES: A number of clinical studies have been performed in an attempt to establish the effects of alkalinization on potency of local anesthetics. Conflicting results were obtained probably because different studies used different methods as well as different definitions of the effects. To determine the efficacy of alkalinization using different local anesthetic solutions and different regional blocks, 180 patients were studied in a randomized, double-blind fashion. The local anesthetic solutions studied were bupivacaine, mepivacaine, and lidocaine; the regional blocks studied were epidural block, axillary brachial plexus block, and femoral and sciatic nerve block. MATERIALS AND METHODS: In this study, 180 patients receiving epidural block (n = 60), sciatic and femoral nerve block (n = 60), and brachial plexus block (n = 60) were randomized to receive, in a double-blind fashion, a plain or a pH-adjusted solution of 2% mepivacaine, 2% lidocaine, or 0.5% bupivacaine. Onset of sensory analgesia, onset of maximum effect (peak effect or complete analgesia), duration of the block, onset, duration and density of motor block were evaluated using pinprick (Hollmen scale) and a 10-point decimal scale (Seow scale). RESULTS: concerning epidural block, the alkalinization of the local anesthetic shortened significantly the onset of sensory analgesia in the dermatome corresponding to the lumbar interspace used for epidural puncture (L3 L4) and increased the spread of the epidural block in all the groups. The onset of sensory analgesia at L4 level ranged from 10 minutes for plain bupivacaine to 3 minutes for alkalinized lidocaine, whereas the onset at T10 level ranged from 16 minutes for plain bupivacaine and mepivacaine to 12.3 minutes for alkalinized lidocaine. The effects of alkalinization were more evident with lidocaine and bupivacaine. Concerning femoral and sciatic nerve blocks, a statistically significant shorter onset of sensory analgesia and motor block were observed with mepivacaine. Concerning brachial plexus axillary block, the effects of alkalinization were more evident with lidocaine. CONCLUSIONS: Alkalinization produced the best results with lidocaine and bupivacaine for epidural block, with lidocaine for brachial plexus block, and with mepivacaine for sciatic and femoral nerve blocks. PMID- 8519713 TI - Epinephrine prolongs duration of subcutaneous infiltration of local anesthesia in a dose-related manner. Correlation with magnitude of vasoconstriction. AB - BACKGROUND AND OBJECTIVES: Epinephrine is frequently combined with local anesthesia to prolong analgesia. Determination of the minimal concentration and the dose of epinephrine that produces prolongation of analgesia is important in the face of epinephrine's potential for systemic and local toxicity. The authors undertook this study to determine a dose-response curve of epinephrine on duration of analgesia of both 1% lidocaine and 0.25% bupivacaine after local infiltration. In order to determine whether epinephrine-induced vasoconstriction affected duration of analgesia, the authors correlated duration of analgesia with magnitude of local vasoconstriction as measured with laser Doppler flowmetry. METHODS: Six volunteers were studied in a randomized double-blind manner. Ten skin wheals of 0.2 mL solution were subcutaneously injected into both forearms of each volunteer. The solutions consisted of 1% lidocaine with epinephrine concentrations of 0, 1:50,000, 1:200,000, 1:800,000, and 1:3,200,000, and 0.25% bupivacaine with the same epinephrine concentrations. Duration of loss of sensation to pinprick at each wheal was recorded. Skin wheals with 0.2 mL of these same solutions were also subcutaneously injected into the abdomen of the same 6 volunteers, and laser Doppler flowmetry readings of skin blood flow were measured for 6 hours after injection. RESULTS: Epinephrine prolonged duration of analgesia for both lidocaine and bupivacaine in a dose-related manner (P < .001). All concentrations of epinephrine attenuated the vasodilation observed in the first 15 minutes after injection with plain local anesthesia (P = .03), and blood flow returned to baseline by 30 minutes after injection of either plain or epinephrine-containing solutions. Duration of analgesia correlated with magnitude of vasoconstriction only at the 15-minute measurement (r = .53 and .57, P = .003 and 0.001 for lidocaine and bupivacaine, respectively). CONCLUSIONS: Epinephrine prolongs duration of analgesia after local infiltration in a dose-related manner. Addition of epinephrine in concentrations of 1:50,000 or 1:200,000 increases duration of analgesia after local infiltration by approximately 200%. Addition of doses as dilute as 1:3,200,000 still increases duration of analgesia by approximately 100%. Duration of analgesia appears to correlate with magnitude of epinephrine-induced vasoconstriction using laser Doppler flowmetry. Based on study data, the use of epinephrine in concentrations from 1:200,000 to 1:3,200,000 is recommended for prolongation of analgesia after local infiltration. PMID- 8519714 TI - Thoracic versus lumbar administration of fentanyl using patient-controlled epidural after thoracotomy. AB - BACKGROUND AND OBJECTIVES: Epidural fentanyl injection can provide analgesia following thoracotomy, but where to insert the catheter is a matter of debate. The study compares the effects of thoracic and lumbar patient-controlled epidural fentanyl on analgesia, fentanyl requirements, and plasma levels after thoracotomy. METHODS: Thirty patients were randomized into two groups to receive either thoracic or lumbar patient-controlled epidural fentanyl for postoperative analgesia. Postoperative pain (10 cm, visual analog scale [VAS]) and fentanyl requirements were assessed every 4 hours for 24 hours and at 12-hour intervals for the next day. Fentanyl plasma levels were measured at 8 and 16 hours after surgery. Results were expressed as mean +/- 1 SD and analyzed using Student's t test, ANOVA, and chi-square analysis at P < .05. RESULTS: Twenty-nine patients completed the study (14 in the lumbar and 15 in the thoracic group). The VAS scores and fentanyl requirements were not significantly different at any time interval in the thoracic group as compared to the lumbar group. VAS scores at 0 hours (4.6) and 4 hours (4.6) in the lumbar group were higher than VAS scores at 12 hours (2.8; P = .04), 16 hours (2.5; P = .02), and 20 hours (2.2; P = .01) in the same group. No significant difference was found between the fentanyl plasma levels of the two groups after 8 hours (lumbar, 0.26 +/- 0.37 ng/mL; thoracic, 0.22 +/- 0.20 ng/mL) or 16 hours (lumbar, 0.36 +/- 0.17 ng/mL; thoracic, 0.44 +/- 0.32 ng/mL). CONCLUSIONS: The authors concluded that there is little if any advantage of thoracic over lumbar patient-controlled epidural fentanyl administration in patients after thoracotomy with respect to analgesia, fentanyl requirements, and plasma levels. PMID- 8519715 TI - Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery. AB - BACKGROUND AND OBJECTIVES: Fentanyl at doses of 6.25 microgram or more, when to hyperbaric bupivacaine for spinal anesthesia for cesarean delivery, has been reported to markedly increase the duration of analgesia. In this study, subarachnoid fentanyl 15 micrograms was evaluated as the sole adjunct to hyperbaric lidocaine spinal anesthesia in parturients undergoing cesarean delivery at term, to determine its effect on the duration of analgesia and side effects perioperatively. METHODS: Twenty-eight parturients scheduled for elective cesarean delivery at term were randomized to one of two groups in a prospective, double-blind fashion. Patients in group F received 15 micrograms fentanyl in addition to 80 mg hyperbaric lidocaine for subarachnoid anesthesia, while patients in group N received 0.3 mL normal saline in addition to 80 mg hyperbaric lidocaine. Visual analog pain scores were recorded preoperatively and at regular intervals until the first patient request for additional analgesia. The occurrence of side effects (nausea, vomiting, pruritus, shivering) was recorded at intervals for 4 hours postinduction. All patients received patient-controlled analgesia after delivery, and analgesic requirements for 24 hours postinduction were recorded. RESULTS: There was no difference between groups with respect to visual analog pain scores intraoperatively. The mean duration of effective analgesia was increased in the patients receiving fentanyl from 71 minutes to 101 minutes (Student's t-test, P < .01). No difference was observed between groups with regard to 4-hour or 24-hour analgesic requirements. Patients in group F were significantly less likely to experience nausea (Fisher's exact test, P < .05) and vomiting (chi-square test, P < .05) in the immediate perioperative period, but no differences were noted between groups in the incidence of pruritus or shivering. CONCLUSIONS: The addition of fentanyl 15 micrograms to hyperbaric lidocaine for subarachnoid anesthesia for cesarean delivery increases the duration of effective analgesia by approximately 30 minutes compared to plain hyperbaric lidocaine, and provides a protective effect regarding nausea and vomiting in the perioperative period. PMID- 8519716 TI - Intravenous ketorolac and subarachnoid opioid analgesia in the management of acute postoperative pain. AB - BACKGROUND AND OBJECTIVES: Ketorolac is a parenteral nonsteroidal anti inflammatory drug that provides analgesia through a peripheral mechanism. The purpose of this study was to evaluate whether the scheduled administration of intravenous ketorolac improves the analgesia provided by subarachnoid opioids after surgery. METHODS: Patients undergoing major urologic surgery were enrolled in a randomized, placebo-controlled, double-blinded study and received one of two analgesic regimens. All patients were given subarachnoid opioid analgesia consisting of morphine (range, 0.55-0.8 mg) plus fentanyl (25 micrograms) at the completion of surgery just prior to awakening. In addition to subarachnoid opioids, patients received four doses of either intravenous placebo (group 1, n = 21) or ketorolac (group 2, n = 17) administered 30 minutes before the anticipated completion of surgery and at 6, 12, and 18 hours after surgery. Patients in group 2 who were 65 years old or older received 30 mg ketorolac initially, with subsequent doses of 15 mg. Those younger than 65 years of age received 60 mg ketorolac initially, with subsequent doses of 30 mg. Pain scores were assessed by a blinded observer using a 10-cm visual analog scale (VAS) at 1, 8, and 24 hours after the operation. Intravenous morphine requirements while in the postanesthesia care unit (PACU) and during the following 24 hours, as well as the incidence of pruritus, nausea, naloxone usage, and bleeding were also recorded. Results were analyzed using the Wilcoxon rank-sum, Fischer's exact, chi-square, and Student's t tests. RESULTS: Patients receiving intravenous ketorolac (group 2) in addition to subarachnoid opioids had significantly lower pain scores 1 hour after surgery, and required less supplementary intravenous morphine within the first 24 postoperative hours (P < .05). The percentage of patients requiring no analgesic intervention while in the PACU was significantly higher for those receiving ketorolac (P = .01). The incidence of opioid-related side effects was similar between groups, and no perioperative bleeding was observed. CONCLUSIONS: When used in conjunction with subarachnoid opioids, the scheduled administration of intravenous ketorolac during the first 24 hours after major urologic surgery significantly enhances analgesia and reduces the need for supplemental intravenous opioids without affecting the incidence of side effects. Intravenous ketorolac is a safe and useful adjuvant to subarachnoid opioids in the management of acute postoperative pain. PMID- 8519717 TI - Wrapping of the legs reduces the decrease in blood pressure following spinal anesthesia. A study in men undergoing urologic procedures. AB - BACKGROUND AND OBJECTIVES: Hypotension after induction of spinal anesthesia remains a common and a potentially serious complication despite acute expansion of intravascular volume. The current study evaluated the role of leg wrapping as an adjunct to acute volume expansion. METHODS: Twenty-four men undergoing elective urologic procedures were randomly assigned to two groups. Patients in the experimental group had their legs wrapped tightly while those in the control group had their legs wrapped loosely with elastic bandages immediately following spinal anesthesia. Significant hypotension was defined as a decrease in mean arterial pressure to less than 65 mm Hg. RESULTS: Systolic blood pressure was significantly lower (P < .05) in the control group at 4, 5, 7, 9, 10, 12.5, and 15 minutes following spinal injection. Diastolic blood pressure was significantly lower (P < .05) in control subjects at 7, 8, 10, and 15 minutes following the block. None of the patients in either group became hypotensive following removal of the elasticized bandages. CONCLUSIONS: Tightly wrapping the legs with elastic bandages immediately after placing spinal anesthesia in mature men is a safe and efficient adjunct in preventing hypotension. PMID- 8519718 TI - The effect of posture on the induction of epidural anesthesia for peripheral vascular surgery. AB - BACKGROUND AND OBJECTIVES: A study was done to determine whether a difference existed in the quality and time to maximum anesthesia between the induction of lumbar epidural anesthesia in the sitting and supine position in patients undergoing infrainguinal arterial reconstruction. METHODS: An epidural catheter was inserted at L3-L4 in 40 patients who were randomly assigned to two groups. In group 1, with the patient sitting, 3 mL lidocaine 1.5% with 5 micrograms/mL epinephrine was given as a test dose, followed 3 minutes later by 12 mL bupivacaine 0.75% injected over 2 minutes through the catheter. After remaining in the sitting position for 5 minutes, the patient was placed supine and the quality of anesthesia assessed at 3-minute intervals for 30 minutes. Anesthesia was assessed by loss of sensation to pinprick and the Bromage scale for loss of motor function. In group 2, after placement of the catheter, the patient was immediately placed supine, the same doses of local anesthesia were given at the same time intervals as in group 1, and the onset of anesthesia was similarly assessed. In addition to a comparison between groups in the quality and time to maximum anesthesia, a correlation was sought between these variables and the age, weight, height, and body surface area (BSA) of the patients in each group. RESULTS: The demographically similar groups showed no difference in maximum cephalad spread of anesthesia (median, interquartile range; group 1: T4, T2.5-T6; group 2: T4, T2.5-T7), motor block (group 1: 3, 2-4; group 2: 4, 4-6), or time to maximum motor block (mean +/- SD; group 1, 17.4 +/- 8.7 minutes; group 2, 17.9 +/ 6.8 minutes). The time to maximum cephalad spread of anesthesia was shorter in group 1 (13.8 +/- 6.9 minutes; group 2, 18.6 +/- 6.6 minutes; P = .03). Neither the age nor weight of the patients in either group had any influence on the quality and time to maximum anesthesia. There was, however, a significant correlation between the height (r = 0.48, P = .0303) and BSA (r = 0.48, P = .0318) of the patients in group 1 and the time to maximum cephalad spread of anesthesia. CONCLUSIONS: When lumbar epidural anesthesia was induced in the sitting rather than supine position, the time to maximum cephalad spread was shorter and correlated directly with the height and BSA of the patient. The position of the patient during induction had no effect on the final level of cephalad spread and degree of motor block. PMID- 8519719 TI - Pain relief for thoracotomy. Comparison of morphine requirements using an extrapleural infusion of bupivacaine. AB - BACKGROUND AND OBJECTIVES: The effectiveness of a continuous infusion of extrapleural bupivacaine for relief of postoperative pain was assessed in patients undergoing posterolateral thoracotomy under general anesthesia by comparing morphine requirements. METHODS: Bupivacaine 0.25% was infused at a rate of 5 mL/h through an unkinkable extrapleural catheter that was sited under direct vision at operation. RESULTS: Mean (+/- SD) 24-hour requirements for morphine from a patient-controlled analgesia device were 39 +/- 15 mg for the treated group and 69 +/- 26 mg in the control group (P < .006). Patients in the treated group recorded significantly smaller visual analog scores for pain both at rest (P < .005) and on movement (P < .03) compared to the control group. There were no adverse effects associated with the use of extrapleural bupivacaine in this study. CONCLUSIONS: Continuous extrapleural infusion of bupivacaine through unkinkable catheters sited during thoracotomy resulted in decreased intravenous patient-controlled analgesia use and decreased verbal categoric pain scores at rest and during movement. PMID- 8519720 TI - Double-blind randomized evaluation of intercostal nerve blocks as an adjuvant to subarachnoid administered morphine for post-thoracotomy analgesia. AB - BACKGROUND AND OBJECTIVES: Thoracotomy is associated with pain and compromised pulmonary function. Intercostal nerve blocks (INB) and subarachnoid morphine (SM) act on different portions of the pain pathway. Each is effective for post thoracotomy pain relief. The combination of these two modalities in relieving post-thoracotomy pain and improving postoperative pulmonary function has not been investigated. METHODS: In a double-blind study, 20 patients undergoing lateral thoracotomy for lung resection were randomized to receive 0.5 mg SM preoperatively and INB with bupivacaine (INB+) prior to wound closure or 0.5 mg SM with INB using saline (INB-). Visual analog scale pain scores at rest, with cough, and with movement of the ipsilateral arm, forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were measured at 4, 24, 48, and 72 hours after the operation. Opioid use was measured during the initial 24 hours after the operation. RESULTS: At 4 hours, the INB+ group demonstrated better FEV1 (56.6% vs. 40.4% of baseline, P < .05) and FVC values (54.6% vs. 39.6% of baseline, P < .05) and less resting and cough pain (P < .05). However, FEV1 continued to decline in the INB+ group at 24 hours to lower than the INB- group although pain scores were similar beyond 4 hours. Opioid usage during the first 24 hours was similar (INB-, 16.7 mg vs. INB+, 13.2 mg, P = .7). CONCLUSIONS: Although postoperative INB provided modest improvements in pain and pulmonary function when used as an adjuvant to 0.5 mg SM for post-thoracotomy analgesia, the benefits were transient. The authors do not recommend adding INB for patients undergoing lateral thoracotomy who receive 0.5 mg SM. PMID- 8519721 TI - Chronic subarachnoid midazolam (Dormicum) in the rat. Morphologic evidence of spinal cord neurotoxicity. AB - BACKGROUND AND OBJECTIVES: In humans, the benzodiazepine midazolam has been reported to exert an antinociceptive action after subarachnoid injections. It has been shown that subarachnoid midazolam given to rabbits produces significant pathology in spinal cord morphology, as detected with light microscopy. In order to further characterize these changes, this study was performed, using a more sensitive histologic technique, including electron microscopy as well as unbiased morphometry. METHODS: The histopathology of the rat lumbar spinal cord was investigated after chronic subarachnoid administration of a commercially available preparation of midazolam. After daily injections of 100 micrograms of midazolam, the animals were transcardially perfused on the twentieth day with a mixture of formaldehyde and glutaraldehyde. RESULTS: Morphometric evaluation of cell number and mean cell volume (MCV) by the disector method revealed a significant lower (P < .05) cell number and a tendency toward higher MCV in the midazolam-injected group (n = 6), compared to the rats injected with saline (n = 6). The higher MCV, in combination with a reduced number of nerve cells, indicated a loss of small neurons. The electron microscopic findings confirmed that midazolam caused neuronal death, since degenerated cell somata, fibers, and terminals were observed in most of the rats. Furthermore, an increased number of microglial cells phagocytosing nerve structures were also seen mainly in the dorsal horn. CONCLUSIONS: The authors found that chronic subarachnoid administration of midazolam gives objective signs of neurotoxicity in the rat spinal cord. The authors' findings are in contrast to those of an earlier light microscopic study in the rat. The present results emphasize both the necessity of morphometric and ultrastructural studies before spinal administration of novel drugs to humans and the neurotoxic potential of midazolam. Since neurotoxicity of midazolam now has been demonstrated in both rats and rabbits, there may be reason to be sceptical of the use of subarachnoid midazolam in humans. PMID- 8519722 TI - 0.1% bupivacaine does not reduce the requirement for epidural fentanyl infusion after major abdominal surgery. AB - BACKGROUND AND OBJECTIVES: Although local anesthesia has been demonstrated to potentiate spinal morphine analgesia in animal studies, results comparing epidural local anesthesia/opioid mixtures with opioid alone are contradictory in clinical studies. The hypothesis was that, although the concentration of bupivacaine (0.1%) was low to minimize its adverse effects, if the infusion rate of a fentanyl/bupivacaine solution was closely adjusted according to need, the presence bupivacaine would reduce the requirement for epidural fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl (10 micrograms/mL) or a fentanyl/bupivacaine (0.1%) mixture epidurally corresponding to the dermatome of the surgical incision in a double-blind fashion for the first 18 hours after major abdominal surgery. The infusion was titrated for each patient to the rate required for pain relief during forced inspiration (pain score < or = 2, maximum 10). Pain scores, the fentanyl doses required, plasma concentrations of fentanyl at 18 hours, and the incidence and severity of adverse effects were recorded. RESULTS: Patients reported similar median pain scores and were equally satisfied with pain relief in both groups. The mean required post operative fentanyl infusion rate (57.7 +/- 19.5 micrograms/h) and the plasma concentrations (0.84 +/- 0.36 ng/mL) in the fentanyl group were comparable to the infusion rate (54.4 +/- 19.2 micrograms/h) and the plasma concentrations (0.86 +/ 0.36 ng/mL) in the fentanyl/bupivacaine group. Respiratory and cardiovascular functions were preserved, and the incidence of nausea, pruritus, and periods of drowsiness or sleep were similar in both groups. CONCLUSIONS: In low concentrations (0.1%), bupivacaine did not reduce the titrated dose of epidural fentanyl required for adequate pain relief during forced inspiration after major abdominal surgery. The incidence and severity of adverse effects were also comparable whether or not low-dose bupivacaine infusion was used. PMID- 8519723 TI - Peak pain relief is delayed and duration of relief is extended following intravenous phentolamine infusion. Preliminary report. AB - BACKGROUND AND OBJECTIVES: Intravenous phentolamine infusion (i.v.P) has been shown to produce pain relief in some patients with sympathetically maintained pain. Animal models of neuropathic pain have reported decreases in pain behavior lasting 5 days following phentolamine injection. However, no clinical study has prospectively assessed pain relief for longer than 24 hours. The aim of this preliminary report was to assess prospectively daily pain relief scores for 1 week following i.v.P METHODS: Thirty-seven consecutive patients with neuropathic pain were asked to complete a pain relief scale for 7 days following i.v.P All patients were first administered 35 mg i.v.P At least 1 week later, 16 patients were administered i.v.P at a higher dose, 50 mg or 75 mg. Data from a total of 45 infusions were collected. RESULTS: Sixteen patients experienced pain relief from i.v.P Twenty-seven infusions resulted in pain relief. Peak pain relief was delayed in 25 of 27 (93%) positive i.v.P: 7 patients experienced the onset of peak response the night immediately following an infusion, 13 the next day, 3 2 days later, and 1 each 4 and 5 days after infusion. All 16 patients who reported pain relief following i.v.P experienced at least 2 days of relief with each infusion. Eight patients experienced at least 1 week of pain relief. No differences in pain relief scores were seen with higher-dosage i.v.P. CONCLUSIONS: A delay in peak pain relief was reported following 25/27 i.v.Ps. Peak pain relief occurred most often at least 24 hours after infusion completion. In these patients, duration of pain relief was at least 2 days. Placebo controlled studies are needed to verify these observations. PMID- 8519724 TI - Epidural analgesia in a preeclamptic parturient after normalization of a prolonged bleeding time with DDAVP. AB - BACKGROUND AND OBJECTIVES: Despite several advantages to the use of epidural analgesia for the management of labor pain in preeclamptic parturients, this procedure is withheld from many such patients owing to associated thrombocytopenia and platelet dysfunction. METHODS: A preeclamptic parturient with mild thrombocytopenia and platelet dysfunction manifested by a prolonged bleeding time received intravenous DDAVP (0.3 microgram/kg) in an attempt to correct her coagulation abnormality. RESULTS: The patient's bleeding time was normalized with DDAVP administration, allowing her to receive epidural analgesia. CONCLUSIONS: Preeclampsia-induced platelet dysfunction might be corrected with DDAVP: A controlled study is required before its routine use can be advocated. PMID- 8519725 TI - Epidural anesthesia in a patient with single ventricle. AB - BACKGROUND AND OBJECTIVES: Single ventricle is a complex congenital cardiopathy characterized by a unit ventricular chamber. Changes of the cardiovascular system in response to epidural anesthesia in these patients have yet to be clearly elucidated. METHODS: A 26-year-old man with single ventricle underwent an orchiopexy under lumbar epidural anesthesia with intravenous sedation. RESULTS: Orchiopexy was successfully performed and the patient was discharged from hospital 4 days later. CONCLUSION: This case report emphasizes the issues of importance to anesthesiologists in regard to this cardiopathy and describes a successful technique of caring for a patient with a complex problem in an emergency situation. PMID- 8519726 TI - The pregnant patient with an intracranial arteriovenous malformation. Cesarean or vaginal delivery using regional or general anesthesia? AB - BACKGROUND AND OBJECTIVES: A parturient with large intracranial arteriovenous malformation presented for elective cesarean delivery. METHODS: The anesthetic technique included acute hydration with intravenous crystalloid followed by continuous epidural anesthesia with bupivacaine and fentanyl and oxygen by face mask. Intraoperative monitoring consisted of electrocardiography, pulse oximetry, invasive arterial blood pressure, and analysis of arterial blood gases. Postoperative analgesia in the immediate postoperative period was provided by a continuous epidural infusion of bupivacaine and fentanyl followed by intravenous patient-controlled analgesia using a mixture of morphine and droperidol. RESULTS: A cesarean delivery was successfully performed and both mother and infant were eventually discharged from the hospital in good condition. CONCLUSIONS: In this case report the choice of obstetric management (cesarean versus vaginal delivery) of a full-term parturient with an intracranial arteriovenous malformation is discussed, and the rationale for the preference of epidural anesthesia for the cesarean delivery is presented. PMID- 8519727 TI - Superficial cervical plexus block for internal jugular and subclavian venous cannulation in awake patients. PMID- 8519728 TI - Failure of the thiopental precipitation test to detect cerebrospinal fluid after dural puncture with current epidural solutions for labor analgesia. PMID- 8519729 TI - Comment on spinal-epidural anesthesia case report by Eldor et al. PMID- 8519730 TI - Severe lumbar pain and epidural anesthesia. PMID- 8519731 TI - Loss-of-resistance technique using both air and saline. PMID- 8519732 TI - Comment on syringe medium. PMID- 8519733 TI - Postdural puncture headache and air travel after spinal anesthesia with a 24 gauge Sprotte needle. PMID- 8519734 TI - Sterile but contaminated epidural trays. PMID- 8519735 TI - Combined spinal-epidural-general anesthesia revisited. PMID- 8519736 TI - Anesthesia and public image. PMID- 8519737 TI - Institutional surgical practices for nonveterinarians. PMID- 8519739 TI - Enhanced neointima formation and attachment on the high-porosity inner surface of modified PTFE vascular grafts. AB - Highly porous PTFE arterial prostheses form endothelium more extensively than the low-porosity grafts in clinical use, but are subject to seroma formation. PTFE vascular grafts were modified to produce a highly porous inner layer (inner layer 60 or 90 microns, outer layer 20 microns). The effect of this modified, composite design on the histology of graft healing was investigated. Twenty-five modified and 25 control grafts, each 4 mm in diameter by 5 cm in length, were implanted into carotid and femoral arteries of dogs. No late seroma formation was observed. After 12 and 18 weeks, the neointima of the grafts was examined by light microscopy and scanning electron microscopy. At 2- and 4-mm distances from the proximal and distal anastomoses, intimal thickness of the control grafts was 238.7 and 96.1 microns, respectively; for the modified grafts it was 236.2 and 202.8 microns at 18 weeks. Thus, the neotinima of modified grafts was thicker than that of control grafts when measured at 4 mm from the anastomoses. Neointimal coverage was less extensive in the control grafts than in modified grafts (26.8 +/- 6.1% vs. 58.8 +/- 13.2%; p < .05). Smooth muscle cells were seen on light-microscopy to penetrate the highly porous inner layer; on scanning electron microscopy, the PTFE fibrils appeared to anchor the neointima of the modified graft. The results suggest that modified PTFE grafts with an inner surface of 60 or 90 microns internodal distance have enhanced formation and anchoring of neointima while remaining impervious to blood. PMID- 8519738 TI - Effect of rejection on electrophysiologic function of canine intestinal grafts: correlation with histopathology and Na-K-ATPase activity. AB - To investigate whether electrophysiologic changes can detect the early onset and progress of intestinal rejection, changes in in vitro electrophysiologic function, intestinal histopathology, and Na-K-ATPase activity were studied in dogs. Adult mongrel dogs of both sexes, weighing 18-24 kg, were used for auto and allo small bowel transplantation. The entire small bowels, except for short segments at the proximal and distal ends, were switched between a pair of dogs (allograft). Animals receiving intestinal autotransplantation were used as controls. Allograft recipients were sacrificed 3, 4, 5, 7, or 9 days after transplantation, and autograft recipients were sacrificed 3, 7, or 14 days after transplantation. Immunosuppression was not used. Electrophysiologic measurements were done with an Ussing chamber. Histological analysis was performed blindly using whole thickness sections. Na-K-ATPase activity in the mucosal tissue, which is said to regulate the potential difference, was also measured. Potential difference, resistance, and Na-K-ATPase activity of the allograft intestine decreased with time and were significantly lower 7 and 9 days after transplantation compared to host intestine, normal intestine, and graft intestine of controls (autograft). Potential difference, resistance, and Na-K-ATPase activity of the native intestinal tissue and the autografts did not decrease with time. Detection of histologically mild rejection of the intestine, which is important for appropriate immunosuppressive treatment in clinical cases, could not be achieved based on electrophysiology or Na-K-ATPase activity. Deterioration of electrophysiologic function during rejection correlated with the histological rejection process and Na-K-ATPase activity; however, electrophysiology may not be a reliable tool for monitoring grafts, since it cannot detect early intestinal rejection. PMID- 8519740 TI - Fibrin sealant of the cut surface of partial liver grafts from living donors. AB - Complete hemostasis and proof against bile leakage on the cut surface of the partial liver graft and the remnant liver of the donor are basic desiderata for a successful outcome in living related liver transplantation (LRLT). This study evaluated the efficacy of fibrin glue sealant on the cut surface of a graft in human living related liver transplantation and canine partial liver transplantation in terms of postoperative complications. From June 1990 to August 1993, a series of 70 LRLTs were performed on children with end-stage liver disease. In harvesting the graft from living donor, hepatic parenchyma was transected by ultrasonic aspirator. Clearly exposed vessels were either ligated or suture ligated. Fibrous connecting tissues of the glissonian branches and tiny vessels were coagulated by a newly devised bipolar electric cautery equipped with saline dripping system. Fibrin sealant was sprayed on the cut surface of the liver graft and the remnant liver of the donor. All donors were discharged from hospital at 10 to 17 (mean = 11.6) days after surgery without any complications that required surgical intervention, and were able to return to normal life. At reperfusion of the graft in the recipients, no blood loss from the cut surface was observed. However, bile oozing on the cut surface was observed in 3 of the 70 cases. No infection or foreign body reactions were observed in the fibrin-sealed cut surface of the graft. Actuarial recipient survival rate was 89% (48/54) in elective cases and 69% (11/16) in emergency cases. In canine transplantation, 16 out of 23 beagles survived for 4 days or longer (longest 20 days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519741 TI - Experimental investigation of intraoperative ultrasound in anatomically precise liver resection. AB - A new technique of segmental liver resection by use of intraoperative ultrasound (IOUS) and injection of methylen blue was evaluated in 15 sheep to study anatomical precision and alterations of the biochemical profile. The results were compared with those of a bisegmentectomy (n = 15) in which segmental boundaries were identified by IOUS alone. In a third group (n = 10) a sham operation (laparotomy without resection) was performed to study the intrahepatic vascular architecture of the liver by IOUS. The quality of the resections and of the ultrasound study was assessed by use of corrosion casts of the livers. The intrahepatic course of the liver veins and their confluence as well as the portal vein and its branches up to the segmental portal pedicles could be detected in all livers. Anatomically precise bisegmentectomies were achieved in 70% of IOUS combined with coloring of the segments versus only 27% in IOUS alone (p < .05). Biochemical and clinical parameters did not reveal any advantage of anatomically precise resection. The results show that intraoperative ultrasound is reliable in visualizing the intrahepatic anatomical characteristics of the liver, but it is imprecise in identifying segmental boundaries or in localizing a segment exactly. Anatomically precise liver resections are technically feasible by use of IOUS plus selective staining of the segments. PMID- 8519742 TI - Significance of reperfusion injury after venous strangulation obstruction of equine jejunum. AB - Fifteen horses under halothane anesthesia were assigned randomly to three groups of 5 horses each as follows. In group 1, the distal 50% of the small intestine was measured through a ventral midline celiotomy and replaced in the abdomen so that these horses could serve as sham-operated controls. In group 2, the same segment of small intestine was subjected to venous strangulation obstruction (VSO) for 180 min. In group 3, the same segment of small intestine was subjected to VSO for 90 minutes, followed by 90 minutes of reperfusion. Biopsies of small intestine were taken from all horses to assess mucosal morphologic injury by light microscopy, to measure tissue levels of malondialdehyde as an indicator of lipid peroxidation, and to measure tissue myeloperoxidase activity as a measure of neutrophil accumulation. VSO for 90 min in horse jejunum increased lipid peroxidation and neutrophil influx to levels that remained constant over the following 90 min, regardless of whether VSO was maintained or was interrupted to allow reperfusion of the tissue. Reperfusion induced a similar mucosal lesion as continued VSO for the same time. From these results, it would appear that VSO causes more severe mucosal damage and inflammation than the subsequent reperfusion period, in contrast to the classical paradigm of reperfusion injury in small intestine. PMID- 8519743 TI - Reexamination of induced fit as a determinant of substrate specificity in enzymatic reactions. AB - It has been argued that a substrate-induced conformational change involving the orientation of catalytic groups cannot affect the specificity for two substrates in an enzymatic system where the chemical step is rate limiting, because such an induced fit would alter the catalytic efficiency for both to an equal extent. To the contrary, the generalized induced-fit treatment described here shows that when critical substrate-specific conformational changes in the enzyme persist in the transition state, specificity is linked to conformational differences between the reactive complex for a good substrate and the related complex for a poor one. Conformational differences are a determinant of specificity when the reaction proceeds via an "induced-fit" transition state. Our treatment also shows that such conformational changes can enhance the specificity of an enzyme with suboptimal catalytic efficiency. If substrate-dependent conformational differences in a primative enzyme can enhance specificity, evolutionary pressure to increase specificity could inseparably link enzymatic specificity to induced conformational changes. PMID- 8519744 TI - The other function of DNA photolyase: stimulation of excision repair of chemical damage to DNA. AB - DNA photolyase is a light-dependent DNA repair enzyme. It binds to cyclobutane pyrimidine dimers in DNA and upon excitation with a blue light photon splits the cyclobutane ring and restores the pyrimidines to native forms. The enzyme is specific for pyrimidine dimers, and it is not known to catalyze any other reaction either in ground or in excited state. However, when photolyase binds to but cannot catalyze repair because of lack of photoreactivating light, it still aids DNA repair by stimulating the nucleotide excision repair system. Recently, it was found that yeast photolyase binds to other lesions in DNA. In particular, the binding to cisplatin damaged DNA was highly specific. However, in vivo experiments revealed that this binding, in contrast to binding, did not stimulate but actually inhibited the removal of cisplatin damage by excision repair and hence photolyase sensitized cells to killing by cisplatin. In the present study, it is demonstrated that Escherichia coli DNA photolyase binds specifically to cisplatin 1,2-d(GpG) intrastrand cross-link and stimulates the removal of the lesion by E. coli excision nuclease in vitro. In agreement with the in vitro data, in vivo experiments revealed that photolyase makes cells more resistant to cisplatin killing. PMID- 8519745 TI - Separation and characterization of the two functional regions of troponin involved in muscle thin filament regulation. AB - Mild proteolytic cleavage of the troponin complex yields TnT1, the N-terminal fragment of troponin T, and TnT2IC, a complex of the C-terminal fragment of troponin T (TnT2) with troponin I (TnI) and troponin C (TnC) [Morris, E. P., & Lehrer, S. S. (1984) Biochemistry 23, 2214-2220]. Both TnT1 and TnT2IC bind tightly to the tropomyosin.actin (Tm.actin) thin filament and influence the interaction of myosin subfragment 1 (S1) with Tm.actin. TnT1 does not affect the rate of S1 binding to Tm.actin but does increase the cooperativity with which S1 "turns on" Tm.actin, monitored by the excimer fluorescence of a pyrene label attached to Cys 190 of Tm [Geeves, M.A., & Lehrer, S. S. (1994) Biophys. J. 67, 273-282]. The apparent cooperative unit size of Tm.actin is increased from 6 to 9 by TnT1 and to 12 by whole troponin. In contrast, TnT2IC has no effect on the cooperativity of Tm.actin but does make the apparent S1-binding rate constant, kapp, Ca(2+)-sensitive; i.e., in the absence of Ca2+, kapp is reduced 2-3-fold by both TnT2IC and whole troponin. Thus, the N- and C-terminal regions of TnT appear to act independently in modulating effects of S1 binding to the Tm.actin thin filament that are important in regulation. PMID- 8519746 TI - The equilibrium folding pathway of staphylococcal nuclease: identification of the most stable chain-chain interactions by NMR and CD spectroscopy. AB - In a previous report [Alexandrescu, A. T., Abeygunawardana, C., & Shortle, D. (1994) Biochemistry 33, 1063-1072], NMR methods were used to characterize the residual structure in delta 131 delta, a large fragment of staphylococcal nuclease that serves as a model denatured state under nondenaturing conditions. On the basis of a large number of missing amide protons for the residues that form a three-strand antiparallel beta sheet in the native state, it was concluded that this beta meander may be highly populated in delta 131 delta, with severe line broadening due to relatively slow exchange between different conformational states. In the present report, results from circular dichroism spectroscopy and NMR spectroscopy indicate strands beta 2-beta 3 form a beta hairpin at urea concentrations below 6 M. Amide proton resonances from several hydrophobic residues adjacent to this beta hairpin disappear in concert with all of the beta 2-beta 3 residues, suggesting a local, non-native hydrophobic interaction may help stabilize the beta hairpin. At concentrations below 3 M, all amide resonances from strand beta 1 in delta 131 delta also disappear, suggesting that beta 1 may combine with the beta 2-beta 3 hairpin to form a native-like beta meander. In addition, the hydrophobic helix alpha 2 decreases from approximately 30% population in 0 M urea to approximately 10%-15% at 6 M urea, whereas helix alpha 1 goes from 10%-15% populated in 0 M urea to undetectable in 6 M urea. Characterization of a second, distinctly different denatured state, WT nuclease at pH 3.0 and low salt, reveals that this low-density acid-denatured state is structurally similar to delta 131 delta at low concentrations of urea. From these and previously published data, a tenative equilibrium folding pathway can be constructed for staphylococcal nuclease which describes the relative strengths and interdependencies of the chain-chain interactions involved in forming the native state. PMID- 8519748 TI - Characterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry. AB - Glutamate 1-semialdehyde aminotransferase produces delta-aminolevulinate for the synthesis of chlorophyll, heme, and other tetrapyrrole pigments. The native enzyme from Synechococcus is pale yellow and has absorption maxima at 338 and 418 nm from vitamin B6. Yellow, colorless, and pink forms of the protein are obtained by treatment with 4,5-dioxovalerate, 4,5-diaminovalerate, and acetylenic GABA, respectively. Compared to the native enzyme, the 418 nm absorption maximum in the yellow enzyme is enhanced and the 338 nm maximum reduced while the colorless enzyme has a heightened maximum at 338 nm and a barely detectable peak at 418 nm. The pink enzyme has an absorption maximum at 560 nm. When the native and colorless enzymes are repeatedly diluted in 0.5 M Na2HPO4, pH 7.0, and reconcentrated, pyridoxamine 5'-phosphate is released and the 338 nm maximum lost. Thus the 338 nm absorption maximum is associated with noncovalently bound pyridoxamine 5'-phosphate. NaBH4 reduction proved that the absorbance at 418 nm is from pyridoxal 5'-phosphate cofactor bound by a Schiff base to the protein. When the native, colorless, and yellow enzymes were subjected to electrospray ionization mass spectrometry, the B6 cofactor dissociated from the protein and gave a molecular weight of 46,401-46,418. Acetylenic GABA and NaBH4 were used for protein modification, and they reacted with the native and yellow enzymes but had no effect on the colorless enzyme. Pyridoxal 5'-phosphate bound covalently to the protein after NaBH4 reduction. Acetylenic GABA attached covalently to the enzyme produced an additional mass peak, 123-126 mass units higher, in the electrospray ionization spectrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519747 TI - Ion channels in the chloroplast envelope membrane. AB - Isolated chloroplast envelope membranes were fused with azolectin liposomes. Ion transport across the membrane of these liposomes was investigated by the patch clamp technique and in planar bilayers. Our results show that the chloroplast envelope contains voltage-dependent anion- and cation-selective channels as well as anion- and cation-selective pores with high conductances. At least one of the high-conductance pores could be located in the chloroplast outer envelope membrane. The low-conductance chloride channel and the potassium channel showed complex gating behavior with subconductant states. Potassium channel gating was affected by monovalent and divalent cations as well as by millimolar concentrations of ATP. Low concentrations of Cs+ induced a flickering block. Voltage dependence of the open probability reveals that macroscopic currents of potassium channels are rectified with preferential potassium uptake into the chloroplast. Flux measurements and determinations of the stroma pH of intact chloroplasts confirm the presence of a potassium channel that is regulated by divalent cations (Mg2+) and by ATP. The fully open potassium channel revealed a conductance of lambda approximately equal to 100 pS in asymmetric KCl (250/20 mM KCl), and the fully open chloride channel revealed a conductance of lambda approximately equal to 60 ps in 100 mM Tris/HCl. One high-conductance channel, mainly active at holding potentials > 60 mV, was slightly selective for glutamate anions (PK+/PGlu- approximately equal to 2) and revealed fast voltage-dependent gating. This high-conductance channel had a conductance of lambda approximately equal to 540 pS (in 250/20 mM potassium glutamate) and was closed most of the time. A second type of high-conductance channel, mainly open and active at holding potentials below 30 mV, was slightly selective for cations (PGlu-/PK+ approximately equal to 2) with a conductance of lambda approximately equal to 1.14 nS (in 250/20 mM potassium glutamate). PMID- 8519749 TI - Design and expression of organophosphorus acid anhydride hydrolase activity in human butyrylcholinesterase. AB - Serine esterases and proteases are rapidly and irreversibly inhibited by organophosphorus (OP) nerve agents. To overcome this limitation, we selected several residues that were predicted to be within 3-10 A of both the active site Ser O gamma and the oxyanion hole of human butyrylcholinesterase for mutation to His (G115H, G117H, Q119H, and G121H). In remarkable contrast with wild-type (WT) and all other His mutants tested, G117H underwent spontaneous reactivation following OP inhibition to regain 100% of original esterase activity with maximum k3 values of approximately 6.8 x 10(-5) and 16 x 10(-5) s-1 for GB (sarin) and VX, respectively, in 0.1 M Bis-Tris, 25 degrees C. The free energy of activation for k3 was 19 kcal mol-1, and measurement of pH dependence suggested that reactivation resulted from an acidic group with pKa 6.2. To evaluate further the importance of His in achieving this result, we changed the same Gly to Lys (G117K) and compared its substrate and inhibitor kinetics with those of G117H. Both mutants retained esterase activity with Km values similar to those of WT for neutral ester hydrolysis, but G117K did not reactivate. Complete reactivation proves that G117H is not irreversibly inhibited but instead functions as a catalyst for OP hydrolysis. Dephosphonylation is the rate-limiting step, and G117H effects overall rate constant enhancements of approximately 100- and 2000 fold above the uncatalyzed hydrolysis of GB and VX, respectively, at pH 6.0, 25.0 degrees C. We conclude that an appropriately positioned imidazolium ion in the oxyanion hole catalyzes dephosphonylation and, thereby, confers a novel organophosphorus acid anhydride hydrolase activity upon butyrylcholinesterase. PMID- 8519750 TI - Structure-function analysis of the mammalian DNA polymerase beta active site: role of aspartic acid 256, arginine 254, and arginine 258 in nucleotidyl transfer. AB - The crystal structure of the catalytic domain of rat DNA polymerase beta revealed that Asp256 is located in proximity to the previously identified active site residues Asp190 and Asp192. We have prepared and kinetically characterized the nucleotidyl transfer activity of wild type and several mutant forms of human and rat pol beta. Herein we report steady-state kinetic determinations of KmdTTP, Km(dT)16, and kcat for mutants in residue Asp256 and two neighboring residues, Arg254 and Arg258, all centrally located on strand beta 7 in the pol beta structure. Mutation of Asp256 to alanine abolished the enzymatic activity of pol beta. Conservative replacement with glutamic acid (D256E) led to a 320-fold reduction of kcat compared to wild type. Replacement of Arg254 with an alanine (R254A) resulted in a 50-fold reduction of kcat compared to wild type. The Km(dT)16 of D256E and R254A increased about 18-fold relative to wild type. Replacement of Arg254 with a lysine resulted in a 15-fold decrease in kcat, and a 5-fold increase in the Km(dT)16. These kinetic observations support a role of Asp256 and Arg254 in the positioning of divalent metal ions and substrates in precise geometrical orientation for efficient catalysis. The mutation of Arg258 to alanine (R258A) resulted in a 10-fold increase in KmdTTP and a 65-fold increase in Km(dT)16 but resulted in no change of kcat. These observations are discussed in the context of the three-dimensional structures of the catalytic domain of pol beta and the ternary complex of pol beta, ddCTP, and DNA. PMID- 8519751 TI - Conformation of xanthene dyes in the sulfhydryl 1 binding site of myosin. 2. AB - The fluorescent dyes 5'-(iodoacetamido)tetramethylrhodamine (5'IATR) and 5' (iodoacetamido)-fluorescein (5'IAF) bind covalently to the reactive sulfhydryl (SH1) of myosin subfragment 1 (S1), the 5'IATR as a dimer and the 5'IAF as a monomer. The conformation of the dimer and the dye-protein complex was investigated by comparison of several spectroscopic signals of the molecules before and after their association into a complex and interpretation of any changes using a coupled dipole oscillator model adapted for this problem [Burghardt & Ajtai (1995) Biophys. Chem. (submitted for publication)]. Absorption and fluorescence spectroscopies were performed on 5'IAF, 5'IATR, and rhodamine 6G (R6G) and rhodamine B (RB) as models of dimer conformation. Absorption, fluorescence, and circular dichroism (CD) spectroscopies were performed on 5'IATR modified S1 (5'R-S1) and 5'IAF-modified S1 (5'F-S1). Combined spectroscopic and 2 D NMR data from rhodamines in solution determined the conformations of the dimers. Xanthene rings from dimers of identical dyes (homodimers) stacked in two structures having very different spectroscopic signatures. Xanthene rings from the heterodimer of R6G and RB stacked in one conformation. The two homodimer conformations of 5'IATR are equally likely to form in solution. The other rhodamine homodimers have one dominant, but not exclusive, structure. Both conformations of the 5'IATR dimer were coupled to a tryptophan as a model of the dye-protein interaction at SH1. The calculated CD from one dimer conformer (dimer A) coupled to tryptophan is negative for the lowest energy CD absorption band. The other dimer (dimer B) gives positive CD on the two lowest energy CD absorption bands. Both dimer structures of 5'IATR contributed to the early time dependent CD signal from 5'IATR binding to SH1, but at equilibrium the CD signal indicated only dimer B, suggesting that the SH1 binding pocket converts dimer A into dimer B. The time-dependent CD signal from 5'IAF changes amplitude but not shape during the reaction with SH1. The model calculation accounting for the spectroscopic signals of 5'R-S1 and 5'F-S1 indicates several likely conformations of the 5'IATR dimer-tryptophan and 5'IAF-tryptophan complexes embedded in S1. These structures fit to the alpha-carbon structure of the SH1 binding pocket when the 5'IATR dimer and 5'IAF interact closely with Trp510 [Rayment et al. (1993) Science 261, 50-58].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519752 TI - NMR solution structure of calcium-saturated skeletal muscle troponin C. AB - Troponin C (TnC) is an 18 kDa (162-residue) thin-filament calcium-binding protein responsible for triggering muscle contraction upon the release of calcium from the sarcoplasmic reticulum. The structure of TnC with two calcium ions bound has previously been solved by X-ray methods. Shown here is the solution structure of TnC which has been solved using 3D and 4D heteronuclear nuclear magnetic resonance (NMR) spectroscopic techniques. The 1H, 13C, and 15N backbone chemical shifts have already been published [Slupsky, C. M., Reinach, F. C., Smillie, L. B., & Sykes, B. D. (1995) Protein Sci. 4, 1279-1290]. Presented herein are the 1H, 13C, and 15N side-chain chemical shifts which are 80% complete. The structure of calcium-saturated TnC was determined on the basis of 2106 NOE-derived distance restraints, 121 phi dihedral angle restraints, and 76 psi dihedral angle restraints. The appearance of calcium-saturated TnC reveals a dumbbell-shaped molecule with two globular domains connected by a linker. The structures of the N terminal and C-terminal domains are highly converged [backbone atomic root mean square deviations (rmsd) about the mean atomic coordinate position for residues 10-80 and 98-155 are 0.66 +/- 0.17 and 0.69 +/- 0.18 A, respectively]; however, the orientation of one domain with respect to the other is not well-defined, and thus each domain appears to be structurally independent. Comparison of the calcium-saturated form of TnC determined herein with the half-saturated form determined by X-ray methods reveals two major differences. First, there is a major structural change which occurs in the N-terminal domain resulting in the opening of a hydrophobic pocket presumably to present itself to its target protein troponin I. This structural change appears to involve only helices B and C which move away from helices N/A/D by the alteration of the backbone phi, psi angles of glutamic acid 41 from irregular in the crystal structure (-97 degrees, 7 degrees) to helical in the NMR calcium-saturated structure (-60 degrees, -34 degrees). The other difference between the two structures is the presence of a flexible linker between the two domains in the NMR structure. This flexible linker allows the two domains of TnC to adopt any orientation with respect to one another such that they can interact with a variety of targets. PMID- 8519753 TI - Analysis of the structure of ribonuclease A in native and partially denatured states by time-resolved noradiative dynamic excitation energy transfer between site-specific extrinsic probes. AB - Formation of local structure and overall chain dimensions in the 124-residue, four-disulfide protein bovine pancreatic ribonuclease A (RNase A) under conditions favoring either the native or partially folded states have been studied by nonradiative excitation energy transfer measurements. Three RNase A derivatives, doubly labeled with 2-naphthylalanine amide (fluorescent donor) at the C-terminus of each and 7-carboxymethylamino-4-methyl-coumarin (fluorescent acceptor) at the epsilon-amino group of lysine 1, 61, and 104, respectively [(1 124)RNase A, (61-124)RNase A, and (104-124)Rnase A], were prepared. RNase A was modified by a two-step labeling strategy involving prior modification of the C terminus with the donor probe by enzymatic methods, followed by modification of lysine epsilon-amino groups with the coumarin derivative. The derivatives were purified by liquid chromatography and characterized by tryptic mapping. The mono labeled donor derivative (without acceptor) undergoes a reversible thermal folding transition (Tm = 48.3 degrees C; native RNase A, Tm = 54.4 degrees C), and all labeled derivatives retain enzymatic activity (activities against the substrate cCMP relative to native are 87 +/- 5%, 94 +/- 6.5%, 79 +/- 10%, and 207 +/- 15% for the donor-only and doubly-labeled derivatives with the acceptor at Lys 104, 61, and 1, respectively), supporting the suitability of these derivatives for protein folding studies. Time-resolved fluorescence measurements were used to determine the extent of nonradiative excitation energy transfer between donor and acceptor probes, which allowed recovery of parameters describing the distribution of interprobe distances and the diffusion coefficient of the ends of the segments defined by the pairs of sites labeled by the probes. Use of a donor with a relatively long intrinsic fluorescence decay rate allowed greater precision in the recovery of the interprobe diffusion coefficients compared with earlier studies using donors with shorter intrinsic decay rates, and this parameter provides an important measure of the extent of folding and degree of packing of the chain segments. Analyses for each derivative were carried out under solution conditions favoring native (pH 5.0, 22 degrees C, < 0.7 M guanidinium hydrochloride) or denatured (> 6 M guanidinium hydrochloride) chain conformations, both with and without intact disulfide bonds (in the absence or presence of dithiothreitol, respectively).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519754 TI - Ubiquinone pair in the Qo site central to the primary energy conversion reactions of cytochrome bc1 complex. AB - The mechanistic heart of the ubihydroquinone-cytochrome c oxidoreductase (cyt bc1 complex) is the catalytic oxidation of ubihydroquinone (QH2) at the Qo site. QH2 oxidation is initiated by ferri-cyt c, mediated by the cyt c1 and [2Fe-2S] cluster of the cytochrome bc1 complex. QH2 oxidation in turn drives transmembrane electronic charge separation through two b-type hemes to another ubiquinone (Q) at the Qi site. In earlier studies, residues F144 and G158 of the b-heme containing polypeptide of the Rhodobacter capsulatus cyt bc1 complex were shown to be influential in Qo site function. In the present study, F144 and G158 have each been singly substituted by neutral residues and the dissociation constants measured for both Q and QH2 at each of the strong and weak binding Qo site domains (Qos and Qow). Various substitutions at F144 or G158 were found to weaken the affinities for Q and QH2 at both the Qos and Qow domains variably from zero to beyond 10(3)-fold. This produced a family of Qo sites with Qos and Qow domain occupancies ranging from nearly full to nearly empty at the prevailing approximately 3 x 10(-2) M concentration of the membrane ubiquinone pool (Qpool). In each mutant, the affinity of the Qos domain remained typically 10-20-fold higher than that of the Qow domain, as is found for wild type, thereby indicating that the single mutations caused comparable extents of the weakening at each domain. Moreover, the substitutions were found to cause similar decreases of the affinities of both Q and QH2 in each domain, thereby maintaining the Q/QH2 redox midpoint potentials (Em7) of the Qo site at values similar to that of the wild type. Measurement of the yield and rate of QH2 oxidation generated by single turnover flashes in the family of mutants suggests that the Qos and Qow domains serve different roles for the catalytic process. The yield of the QH2 oxidation correlates linearly with Qos domain occupancy (QH2 or Q), suggesting that the Qos domain exchanges Q or QH2 with the Qpool at a rate which is much slower than the time scale of turnover.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519755 TI - Ion pair formation between basic residues at 144 of the Cyt b polypeptide and the ubiquinones at the Qo site of the Cyt bc1 complex. AB - Loci of spontaneous Qo site inhibitor resistant mutants in the cyt bc1 complex of the photosynthetic bacterium Rhodobacter capsulatus are M140, F144, G152, G158, and T163 of the cyt b polypeptide. In this report, we have studied the effects of arginine (R) substitution at these positions with a view to test for specific interactions with the [2Fe-2S] cluster, cyt bL with Qo site ubiquinone (Q), or hydroquinone (QH2). All the arginine mutants displayed severely or completely impeded photosynthetic growth resulting from dysfunctional cyt bc1 complexes. The source of dysfunction in G158R and T163R was identified by a > 1000-fold decrease in the Qo site affinity for QH2 and Q, sufficient to empty the site in the presence of the 30 mM ubiquinone pool of the chromatophore membrane; they appear similar to the class of mutants described in the preceding paper [Ding, H., Moser, C. C., Robertson, D. E., Tokito, M., Daldal, F., & Dutton, P. L (1995) Biochemistry 34, 15979-15996]. The source(s) of dysfunction of M140R and G152R is not so apparent since they possess Qo sites with normal QH2/Q affinity; they appear to be members to the class of mutants identified and characterized in the following paper [Saribas, S., Ding, H., Dutton, P. L., & Daldal, F. (1995) Biochemistry 34, 16004-16012]. The present paper focuses on the unique affects of F144R. Redox potential and EPR spectral properties of the Qo site of F144R showed that arginine forms an ion pair with the head group of an anionic ubiquinone, tentatively suggested to be a ubihydroquinone anion (QH-) in the Qos domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519756 TI - Tyrosine 147 of cytochrome b is required for efficient electron transfer at the ubihydroquinone oxidase site (Qo) of the cytochrome bc1 complex. AB - In Rhodobacter capsulatus, tyrosine (Y) 147 is a highly conserved residue of the cyt b subunit of the bc1 complex. It is located in the vicinity of residues altered in spontaneous inhibitor resistant mutants that affect the ubihydroquinone oxidase (Qo) site of this enzyme. In this work, Y147 was substituted with phenylalanine (F), valine (V), serine (S), and alanine (A) using site-directed mutagenesis in an effort to investigate its specific role in the Qo site. Of the four mutants obtained, Y147S and Y147A exhibited very low ubihydroquinone:cyt c reductase activities and were unable to support photosynthetic growth (Ps) while Y147F and Y147V were Ps+. In all mutants, no changes in the redox midpoint potentials (Em7) of the cyt bH and cyt bL, the occupancy of the Qo site by Q/QH2, and the flash-induced reverse electron transfer kinetics from Qi to cyt bH were observed. On the other hand, rates of electron transfer from Qo to cyt bH were mildly reduced (2-3-fold) in Y147F and V but dramatically decreased (about 20-fold) in Y147A and S, localizing the defect to the Qo site. Thus, Y147A and S are members of a novel class of Qo site mutants that affect the Qo site catalysis without perturbing the accessibility or binding of the substrate. Additional insight to the role of Y147 on ubihydroquinone oxidation was gained by analyzing the Ps+ revertants of these mutants. Two pseudorevertants contained a second mutation [isoleucine (I) or valine (V)] at the highly conserved M154 position, six residues away from Y147.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519757 TI - Identification of a common cytochrome P450 epitope near the conserved heme binding petide with antibodies raised against recombinant cytochrome P450 family 2 proteins. AB - The cytochrome P450 (P450) proteins constitute a superfamily of enzymes involved in various oxidations and related activities. Polyclonal antibodies raised against bacterial recombinant human P450s varied in specificity, depending upon the individual rabbits used. Several of the antisera raised against P450s 2C10 and 2E1 recognized a number of P450 family 1, 2, and 3 proteins, and two of the less selective antibodies were used to identify cross-reactive epitopes. P450 2C10 peptides reacting with anti-P450 2E1 and P450 2E1 peptides reacting with anti-P450 2C10 were isolated after electrophoresis/immunoblotting and analyzed by Edman degradation. Several of these were in a region near the highly conserved Cys that is a putative axial ligand to the heme. Peptides corresponding to the most conserved regions in this area were synthesized. Anti-P450 2C10 sera did not recognize 14-mer peptides corresponding to the heme-binding region (2C10 410-423 or 2E1 409-422) or the 14-mer peptides immediately C-terminal to these (2C10 425 438 or 2E1 424-437), but anti-P450 2E1 sera showed weak reaction with the latter two synthetic peptides. A longer peptide (29-mer) of P450 2E1 containing parts of both regions (412-440) reacted with both anti-P450 2C10 and anti-P450 2E1 antisera. Antibodies raised against a conjugate of the 29-mer peptide (with hemocyanin) recognized this antigen, the more C-terminal 14-mer peptides (2C10 425-438 and 2E1 424-437), P450s 2C10 and 2E1, and P450s 1A1, 11A1, and 17A. The 29-mer peptide showed considerable alpha-helix structure as judged by CD spectroscopy, in contrast to any of the 14-mers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519758 TI - Degradation of the D1- and D2-proteins of photosystem II in higher plants is regulated by reversible phosphorylation. AB - The effects of protein phosphorylation and dephosphorylation upon high-light induced degradation of the photosystem II reaction center proteins D1 and D2 have been studied in isolated thylakoid membranes and photosystem II core complexes. The rate of photoinactivation of photosystem II electron transport is not affected by thylakoid membrane phosphorylation. However, the degradation rate of the D1-protein in its phosphorylated form is drastically reduced under conditions which induce either acceptor- or donor-side photoinhibition of photosystem II. The degradation rate of the D2-protein is also reduced following protein phosphorylation. The stability of the phosphorylated D1-protein is further increased under conditions of reduced phosphatase activity, suggesting that phosphorylated and damaged D1-protein has to be dephosphorylated prior to proteolytic degradation. Our results expand on experiments performed in vivo, which suggest that following photoinhibition the controlled repair of damaged photosystem II centers requires not only proteolytic enzymes but also kinase and phosphatase activities. It is suggested that the phosphorylation of the D1- and D2-proteins allows tight coordination of the degradation of damaged proteins with insertion of new copies of proteins into photosystem II. PMID- 8519759 TI - ESEEM study of the plastoquinone anion radical (QA.--) in 14N- and 15N-labeled photosystem II treated with CN. AB - The nonheme iron of the photosystem II reaction center was converted to its low spin state (S = 0) by treatment with CN-. This allowed the study of the plastoquinone, QA- anion radical by electron spin-echo envelope modulation (ESEEM) spectroscopy. A comparative analysis of the ESEEM data of QA- in 14N- and 15N-labeled PSII demonstrates the existence of a protein nitrogen nucleus coupled to the QA-. The 14N coupling is characterized by a quadrupolar coupling constant e2qQ/4h = 0.82 MHz, an asymmetry parameter eta = 0.45, and hyperfine coupling constant A approximately 2.1 MHz. The 15N hyperfine coupling is characterized by T = 0.41 MHz and alpha iso approximately 3.3 MHz. The possible origins of the nitrogen hyperfine coupling are discussed in terms of the amino acids thought to be close to the QA- in PSII. Based on a comparison of the 14N ESEEM with 14N-NQR and 14N-ESEEM data from the literature, the most likely candidate is the amide nitrogen of the peptide backbone of Ala261 of the polypeptide D2, although the indole nitrogen of Trp254 and the imino nitrogen of His215 of D2 also remain candidates. PMID- 8519760 TI - Adenosine 5'-(gamma-thiotriphosphate): an ATP analog that should be used with caution in muscle contraction studies. AB - The slowly hydrolyzed ATP analog adenosine 5'-(gamma-thiotriphosphate) (ATP gamma S) has been used in many studies of the muscle motor protein myosin in order to form a stable "weak binding" state analogous to the actin-S1-ATP complex However, the results from studies using ATP gamma S do not always agree with the results of experiments using ATP. The binding of myosin subfragment-1-ATP gamma S to actin has now been studied in some detail to determine its relationship to the actin-S1-ATP state. The binding of myosin subfragment-1-ATP gamma S to actin troponin-tropomyosin is similar in affinity to the binding of myosin subfragment 1-ATP. Like myosin subfragment-1-ATP, the binding is not Ca(2+)-dependent, and most importantly, myosin subfragment-1-ATP gamma S does not stabilize the active configuration of actin-troponin-tropomyosin. Thus, myosin subfragment-1-ATP gamma S is an analog of myosin subfragment-1-ATP but must be used with caution for two reasons: (1) The binding of ATP gamma S to regulated actomyosin subfragment-1 is Ca(2+)-sensitive, and errors can be made in the interpretation of results if proteins are not fully saturated with nucleotide and a mixture of weak and strong binding states is present. (2) At the high concentrations of myosin subfragment-1 used in some experiments, significant amounts of ADP may form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519761 TI - Phospholipid binding, phosphorylation by protein kinase C, and filament assembly of the COOH terminal heavy chain fragments of nonmuscle myosin II isoforms MIIA and MIIB. AB - Previously, we showed that myosin II heavy chains bind to phosphatidylserine (PS) liposomes via their COOH terminal regions and that protein kinase C (PK C) phosphorylates the PS-bound heavy chains [Murakami et al. (1994) J. Biol. Chem. 269, 16082-16090]. In this report, we studied the phospholipid binding, the kinetics of phosphorylation by PK C, and the effect of PK C-mediated phosphorylation on assembly using 46-47 kDa fragments from the COOH termini of macrophage (MIIAF46) and brain type (MIIBF47) heavy chain isoforms. Binding of the fragments to PS or phosphatidylinositol liposomes increased turbidity, but MIIAF46 gave higher turbidity than MIIBF47. Both fragments were sedimented similarly by ultracentrifugation in PS concentration and mole percent of PS dependent manners. With mixed PS/phosphatidylcholine (PC) liposomes, at least 70 mol % PS was required for heavy chain binding. A similar level of PS was required for phosphorylation of fragments by PK C, indicating that binding of tail regions to PS is a prerequisite for phosphorylation by PK C. PK C phosphorylated MIIBF47 with Vmax values 4-5 times higher than those of MIIAF46, but the Km values for the two substrates were similar. The apparent Km values for PS liposomes (Klipid) were also similar for phosphorylation of both isoforms. Mixing PS with PC increased the Klipid and reduced the Vmax values but did not alter the Km values for the substrates. Assembly of MIIBF47, but not MIIAF46, was significantly inhibited by the phosphorylation, indicating that nonmuscle myosin assembly can be regulated, in an isoform specific manner, via phosphorylation of heavy chains by PK C. PMID- 8519762 TI - Kinetic characterization of the catalytic domain of Dictyostelium discoideum myosin. AB - The myosin head consists of a globular motor or catalytic domain that contains both the catalytic and actin binding sites, and a neck region which consists of a 8.5 nm alpha-helix that emerges from the globular part of the heavy chain and is stabilized by the binding of the essential and regulatory light chains. High levels of M754, a recombinant polyhistidine-tagged catalytic domain-like fragment of myosin II, were produced in Dictyostelium discoideum and purified using a rapid extraction protocol and metal chelate chromatography. Approximately 1.2 mg of homogeneous, functional protein was obtained per gram of cells. Kinetic analysis of M754 showed that the recombinant protein still has all the typical properties of a myosin ATPase. However, the removal of the light chain domain does have a pronounced effect on enzymatic activity. Nucleotide on-rates are 7-16 fold slower for M754 than for a myosin head fragment that includes the neck region. In contrast, the rate of ATP binding and dissociating the actin-bound catalytic domain is 10-fold increased. Overall the results indicate that the truncation of the heavy chain affects the nucleotide binding site and the communication between the nucleotide and actin binding sites. Furthermore, it seems that the nucleotide site of M754 is not fully formed but binding to actin or ATP stabilizes the structure in general and the nucleotide binding site in particular. PMID- 8519763 TI - Magic-angle spinning and solution 13C nuclear magnetic resonance studies of medium- and long-chain cholesteryl esters in model bilayers. AB - The incorporation of cholesteryl esters (CE) with saturated acyl chains into the lamellar structure of phospholipids was studied by 13C nuclear magnetic resonance (NMR) spectroscopy. The CE (octanoate, palmitate, and stearate) were 13C-enriched in the carboxyl carbon to enhance the signals of the small amounts of bilayer incorporated CE. Magic-angle spinning (MAS) NMR was used to detect signals in unsonicated multilamellar phosphatidylcholine (PC), and solution NMR was used to detect signals in PC small unilamellar vesicles (SUV). All CE showed a carbonyl peak reflecting localization of the carbonyl at the aqueous interface (Hamilton & Small, 1982). The maximal incorporation decreased with chain length, from 5 mol % for octanoate to 1.4 mol % for stearate in multilayers; the stearate ester had a solubility slightly lower than that of cholesteryl oleate (2 mol %). The maximal incorporation of a specific CE was 1.2-2.0 times higher in SUV than in multilayers. Cholesteryl oleate did not prevent solubilization of cholesteryl stearate in the PC interface. CE in excess of the solubility maximum in multilayer samples was shown to be crystalline at 35 degrees C by MAS NMR; thus, in the bilayer the CE gained considerable mobility compared to its mobility in its pure bulk phase at body temperature. Furthermore, CE with two saturated chains were not distinguishable from esters with an unsaturated chain with respect to mobility and position in the interface. These fundamental interfacial properties assure utilization of CE with common dietary fatty acyl chains. PMID- 8519764 TI - Nickel is a specific inhibitor for the binding of activated alpha 2-macroglobulin to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. AB - The low density receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR) binds to several ligands involved in lipoprotein and protease clearance. The receptor-associated protein (RAP) inhibits the binding of all known ligands. We studied the inhibition by Ni2+ of the binding of different ligands to cells and to the purified LRP/alpha 2-MR. Ni2+ inhibited all of the specific binding of radiolabeled methylamine-activated alpha 2-macroglobulin (125I-alpha 2-M*) to rabbit aortic smooth muscle cells (SMC), rat hepatoma Fu5AH, and mouse fibroblast L cells. Ni2+ also inhibited the binding of trypsin activated alpha 2-macroglobulin to SMC but did not affect the binding of RAP, Pseudomonas exotoxin A, or low-density lipoproteins. The inhibition of alpha 2-M* binding by Ni2+ was not due to its interaction with alpha 2-M*. Preincubation of SMC with Ni2+ followed by ligand binding suggested that Ni2+ binds to cell surface molecules and inhibits the binding of alpha 2-M* but does not affect RAP binding. Most of the binding of alpha 2-M* to SMC was due to its binding to the LRP/alpha 2-MR, as opposed to the recently described signaling receptor, as demonstrated by the inhibition of this binding by the RAP. Moreover, the inhibition of alpha 2-M* binding to the LRP/alpha 2-MR by Ni2+ was demonstrated using purified receptor immobilized on microtiter plates. Two to three molecules of 63Ni2+ bound to the immobilized receptor with equal affinity but not to alpha 2-M*. The specific binding of alpha 2-M* to the immobilized receptor was inhibited in the presence of nickel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519765 TI - Binding of cobalamin and cobinamide to transcobalamin from bovine milk. AB - We have studied the interaction between transcobalamin (TC) and the ligands cobalamin (Cbl) and cobinamide (Cbi). Partially purified TC from bovine milk was depleted of endogenous Cbl by 8 M urea treatment. Unsaturated TC was adsorbed on CM-Sepharose in order to ensure fast separation of the matrix-bound protein from the reaction medium. The forward reaction TC+Cbl-->TC-Cbl (rate constant k+Cbl) and the backward reaction TC-Cbl-->TC+Cbl (k-Cbl) were followed in time. A single step binding model (with no intermediate protein-ligand complex) was sufficient to fit the data. The calculated rate constants were k+Cbl = 0.6 nM-1 min-1 and k Cbl = 1.3 x 10(-4) min-1, which corresponded to the TC-Cbl dissociation constant KDCbl = 0.2 pM. Reaction between TC and Cbl developed against electrostatic forces, and the effective charges of the interacting species were estimated as both +1 or both -1. The competition between Cbl and Cbi for TC was studied, which resulted in determination of the relevant rate constants for Cbi: k+Cbi = 0.03 nM 1 min-1, k-Cbi = 0.03 min-1, and KDCbi = 1 nM. Slow dissociation of TC-Cbl guarantees its stability in plasma for 5-10 h, while Cbi bound to TC would be transferred to haptocorrin in less than 1 h. PMID- 8519766 TI - Transition state and rate-limiting step of the reaction catalyzed by the human dual-specificity phosphatase, VHR. AB - The dual-specificity phosphatases are unusual catalysts in that they can utilize protein substrates containing phosphotyrosine as well as phosphoserine/threonine. The dual-specificity phosphatases and the protein-tyrosine phosphatases (PTPases) share the active site motif (H/V)C(X)5R(S/T), but display little amino acid sequence identity outside of the active site. Although the dual-specificity phosphatases and the PTPases appear to bring about phosphate monoester hydrolysis through a similar mechanism, it is not clear what causes the difference in the active-site specificity between the two groups of enzymes. In this paper, we show that the human dual-specificity phosphatase, VHR [for VH1-Related; Ishibashi et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12170-12174], is rather promiscuous toward small phosphate monoesters (including both aryl and alkyl phosphates of primary alcohols) with effectively identical kcat/Km and kcat values while the pKa values of the leaving groups (phenols or alcohols) varied from 7 to 16. Linear free-energy relationship analysis of kcat and kcat/Km of the enzyme catalyzed hydrolysis reaction suggests that a uniform mechanism is utilized for both the aryl and alkyl substrates. The very small dependency of kcat/Km on the leaving group pKa can be accounted for by the protonation of the leaving group. Pre-steady-state burst kinetic analysis of the VHR-catalyzed hydrolysis of p nitrophenyl phosphate provides direct kinetic evidence for the involvement of a phosphoenzyme intermediate in the dual specificity phosphatase-catalyzed reaction. The rate-limiting step for the VHR-catalyzed hydrolysis of p nitrophenyl phosphate corresponds to the decomposition of the phosphoenzyme intermediate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519767 TI - Primer synthesis kinetics by Escherichia coli primase on single-stranded DNA templates. AB - The kinetics of primer RNA initiation and elongation by Escherichia coli primase were measured. The single-stranded DNA template that was used to develop the system, d(CAGA-(CA)5CTGCAAAGC), contained: (1) the preferred initiating trinucleotide d(CTG); (2) five residues 3' to the d(CTG), the minimum required for efficient primer synthesis; and (3) a single guanine placed near the 5'-end to facilitate study of cytidine triphosphate analog incorporation at a unique site. The assay monitored radiolabeled nucleotide incorporation into the RNA primers. The various primers were separated by length using denaturing polyacrylamide gel electrophoresis. Different types of primers were observed when synthesis was monitored using gamma- versus alpha-radiolabeled nucleotides as the probe. When [gamma-32P]-ATP incorporation was the probe, only primers initiated with ATP from the unique template thymine were observed. The sequences of these primers were complementary to that of the template. No primers shorter than a 12 mer accumulated, demonstrating that formation of the first phosphodiester bond was much slower than that of the next 10 phosphodiester bonds. The longest primer observed when monitoring [gamma-32P]ATP incorporation was 16 nucleotides long, the correct length for a primer completely template-directed and initiated at the unique thymine. Misinsertion of a noncognate nucleotide at the template's guanine indicated very poor nucleotide discrimination by this enzyme. When [alpha-32P]UTP was the probe for primer synthesis, all primers synthesized were observed whether or not they were initiated with ATP. Under these conditions, "overlong" primers and the above-described template length-dependent primers were observed. The template length-dependent primers accumulated faster than the overlong primers, but, at long incubation times, the overlong primers became the dominant species. The overlong primers were not fully related to the template length-dependent primers since they were not initiated complementary to the template d(CTG). Nevertheless, the overlong primers did appear to arise as a consequence of the template length-dependent species since their length was double and they arose in the time course after the length-dependent species. PMID- 8519768 TI - Berenil binding to higher ordered nucleic acid structures: complexation with a DNA and RNA triple helix. AB - Berenil is an antitrypanosomal agent that binds to nucleic acid duplexes. Recently, we reported that this drug can bind to both DNA and RNA duplexes, while exhibiting properties characteristic of both intercalation and groove binding [Pilch, D. S., Kirolos, M. A., Liu, X., Plum, G. E., & Breslauer, K. J. (1995) Biochemistry 34, 9962-9976]. In this work, we use spectroscopic, calorimetric, and hydrodynamic techniques to demonstrate that berenil also can bind to DNA and RNA triplexes. Our results reveal the following significant features: (i) Berenil binds to the poly(dA).2poly(dT) DNA triplex and to the poly(rA).2poly(rU) RNA triplex without displacing the major groove-bound third strands. (ii) Both berenil-bound triplexes melt via two distinct transitions: initial conversion of the triplex to the duplex state, with the berenil remaining bound, followed by denaturation of the duplex to its component single strands. (iii) The magnitude and even the direction of the impact of berenil binding on the thermal stability of the DNA triplex depends on both the Na+ concentration and the drug binding density (the [base triplet]/[total berenil] ratio). Specifically, at Na+ concentrations < or = 0.08 M, the DNA triplex to duplex transition is thermally stabilized, while at Na+ concentrations > or = 0.125 M it is thermally destabilized. Between these two salt concentrations, berenil binding either enhances or diminishes the thermal stability of the DNA triplex in a manner that depends on the [base triplet]/[total berenil] ratio. (iv) The effect of berenil binding on the thermal stability of the RNA triplex to duplex equilibrium also depends on the [base triplet]/[total berenil] ratio, having a weakly destabilizing effect on this equilibrium at [base triplet]/[total berenil] ratios > 5, while thermally stabilizing this equilibrium at [base triplet]/[total berenil] ratios < 5. (v) The apparent "site sizes" associated with berenil binding to the triplexes range from approximately 1 to 12 base triplets per bound berenil and depend, in part, on the host triplex. One of the site sizes common to both triplexes is consistent with berenil binding to the minor groove. (vi) Berenil exhibits a higher apparent binding affinity for the DNA triplex relative to the RNA triplex. (vii) Viscometric data reveal nonintercalative binding properties when berenil complexes with both triplexes, consistent with a minor groove binding mode. (viii) Berenil binding to either the DNA or the RNA triplex is enthalpically more favorable than berenil binding to the corresponding duplex. (ix) Berenil binding to both triplexes decreases the cooperativity of the triplex to duplex melting event.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8519769 TI - Anomalous rapid electrophoretic mobility of DNA containing triplet repeats associated with human disease genes. AB - Eight human genetic diseases have been associated with the expansion of CTG or CGG triplet repeats. The molecular etiology behind expansion is unknown but may involve participation of an unusual DNA structure in replication, repair, or recombination. We show that DNA fragments containing CTG triplet repeats derived from the human myotonic dystrophy gene migrate up to 20% faster than expected in nondenaturing polyacrylamide gels, suggesting the presence of an unusual DNA helix structure within the CTG triplet repeats. The anomalous migration is dependent upon the number of triplet repeats, the length of the flanking DNA, and the percentage and temperature of the polyacrylamide. The effect could be reduced by the addition of actinomycin D. Applying a reptation model for electrophoresis, the results are consistent with a 20% increase in persistence length of the DNA. PCR products containing CTG or CGG repeats from the spinocerebellar ataxia type I gene (SCA1) or the fragile X FMR1 gene, respectively, also showed higher electrophoretic mobility. These are the first sequences of defined length for which a dramatic increase in mobility can be attributed to sequence-dependent structural elements in DNA. PMID- 8519770 TI - Human platelet glycoproteins V and IX: mapping of two leucine-rich glycoprotein genes to chromosome 3 and analysis of structures. AB - Human platelet glycoproteins Ib alpha, Ib beta, V, and IX comprise an interrelated set of molecules (the Ib-V-IX system) that together form a surface adhesion receptor for the ligand, von Willebrand factor. To complete the primary structural characterization of the genes involved in this system, we have analyzed cosmid clones for both the glycoprotein V and IX genes and used these clones to localize the two genes by fluorescence in situ hybridization. Both genes were found on the long arm of chromosome 3, but at distinct sites, the GPV gene on 3 band q29 and the GP IX gene on 3 band q21. The transcriptional start site of the GPV gene was defined by "anchored" PCR and primer extension. The GPV gene contains two exons, the first consisting of approximately 37 bases and the second of approximately 3500 bases, interrupted by a single 958 base intron. The GPV transcript has multiple start sites spread over a twenty base region. The 5' flanking region of the GPV gene has a series of potential consensus regulatory elements including GATA, ets, and Sp-1 sites, similar to those found in other described megakaryocyte/platelet genes, including those of the Ib-V-IX system. In assessing the four Ib-V-IX genes as a group, all four have a simple, "intron depleted" structure with the entire open reading frame of the mature polypeptide located within a single exon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519771 TI - Vaccinia virus DNA ligase: specificity, fidelity, and inhibition. AB - Vaccinia DNA ligase and mammalian DNA ligases II and III comprise a distinct subgroup of structurally homologous enzymes within the eukaryotic DNA ligase family. The specificity and fidelity of the viral enzyme were investigated using purified recombinant ligase and synthetic duplex DNA substrates containing a single strand discontinuity. Vaccinia ligase catalyzed efficient strand joining on nicked DNAs in the presence of magnesium and ATP (Km = 95 microM). dATP, ITP, AMPPCP, 3'dATP, and ATP alpha S could not substitute for ATP; of these, 3'dATP and ATP alpha S were inhibitors of ligation. The vaccinia enzyme was unable to seal strands across a 1 nt (nucleotide) or 2 nt gap. Ligase action at a 1 nt gap resulted in accumulation of high levels of the normally undetectable DNA adenylate reaction intermediate. In contrast, no DNA-adenylate was formed at a 2 nt gap. A native gel mobility shift assay showed that vaccinia DNA ligase was capable of discriminating between nicked and gapped DNAs at the substrate binding step. The ligase was fairly tolerant of mismatches at a nick involving the 5' phosphate donor terminus but was inhibited strongly by mismatches at the 3' OH acceptor terminus, especially by purine.-purine mispairs. These findings underscore the importance of a proper 3' OH terminus in substrate recognition and reaction chemistry but also raise the possibility that ligase may generate mutations during DNA repair by sealing DNA molecules with mispaired ends. Ligase was inhibited by several DNA binding drugs, including, in order of decreasing potency, distamycin, ethidium bromide, and actinomycin. Strand joining by purified ligase was not affected by etoposide, a drug that inhibits vaccinia virus replication in vivo and which depends on the presence of vaccinia ligase for its antiviral action. PMID- 8519772 TI - Influence of the oxidatively damaged adduct 8-oxodeoxyguanosine on the conformation, energetics, and thermodynamic stability of a DNA duplex. AB - As part of an overall program to characterize the impact of mutagenic lesions on the physiochemical properties of DNA, we report here the results of a comparative spectroscopic and calorimetric study on a family of DNA duplexes both with and without the oxidative lesion 2'-deoxy-7-hydro-8-oxoguanosine (8-oxodG). Specifically, we have studied a family of eight 13-mer duplexes of the form [5' GCGTAC[G* or G]CATGCG-3'].[3'-CGCATG[C, A, T, or G]GTACGC-5'] in which G* is the 8-oxodG lesion. These eight duplexes, which we designate by the identity of the variable central base pair (e.g., G*C), reflect two subsets: four duplexes in which the modified guanine base is positioned opposite each of the four possible canonical residues (G*C, G*A, G*G, G*T) and the corresponding four "control" duplexes in which the guanine is not modified (GC, GA, GG, GT). The data derived from our spectroscopic and calorimetric measurements on these eight duplexes allow us to evaluate the influence of the 8-oxodG lesion, as well as the base opposite the lesion, on the conformation, the thermal and thermodynamic stability, and the melting thermodynamics of the host DNA duplex. We find that modification of dG to 8-oxodG (G*) does not change the global DNA duplex conformation as judged by circular dichroism spectra. Despite this structural similarity, our data reveal that the dG to dG* modification does influence duplex thermal and thermodynamic properties, some of which depend on the base opposite the lesion. Thus, apparent structural identity does not mean that two duplexes necessarily will exhibit equivalent thermal and/or thermodynamic properties. In general, we find that the thermodynamic effects induced by the lesion (e.g., GC vs G*C) or by mismatched base pairs (e.g., GC vs GG) can result in relatively large changes in enthalpy which are partially or wholly compensated entropically to produce relatively modest changes in free energy. Our data also suggest that the biologically observed differential recognition of 8-oxodG duplexes and the preferential nucleotide insertion opposite 8-oxodG residues cannot be rationalized simply in terms of large thermodynamic differences. PMID- 8519773 TI - Characterization of proteins in detergent-resistant membrane complexes from Madin Darby canine kidney epithelial cells. AB - We previously isolated detergent-resistant membrane complexes (DRMs) that were not solubilized after extraction of Madin-Darby canine kidney cells with Triton X 100 on ice. The complexes were rich in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol (GPI)-anchored proteins. In this study, we examined the protein composition of DRMs and further characterized the detergent solubility of these structures. Eight to ten cell-surface proteins, including proteins from both apical and basolateral membranes, were recovered in DRMs. Most DRM proteins, however, were not exposed to the surface of whole cells, and we did not detect the complex of cell-surface proteins described by Sargiacomo et al. in a similar study [Sargiacomo, M., et al. (1993) J. Cell Biol. 122, 789-807]. Almost all proteins in DRMs were solubilized by Triton X-100 at temperatures above 30 degrees C or by octyl glucoside on ice. In contrast, a GPI-anchored protein, placental alkaline phosphatase, was mostly solubilized by Triton X-100 after extraction at 10 degrees C. This protein was insoluble in ice-cold Triton X 100 when first delivered to the plasma membrane and remained so for at least 6 h after synthesis. A fraction of the lipids in DRMs remained insoluble after extraction with Triton X-100 at 37 degrees C. DRM lipids were not solubilized by octyl glucoside, suggesting that this detergent selectively extracts proteins from DRMs. PMID- 8519774 TI - Nonisotropic enzyme--inhibitor interactions: a novel nonoxidative mechanism for quantum proteolysis by human neutrophils. AB - Traditional theories of enzyme kinetics do not model the influences of rapidly changing and nonisotropic enzyme concentrations in real-world systems. We have modeled local enzyme concentrations in space and time following quantal release of human leukocyte elastase (HLE) from cytoplasmic granules of polymorphonuclear neutrophils (PMN). Calculations from first principles indicate that approximately 67,000 molecules of HLE are stored in each azurophil granule at a mean concentration of 5.33 mM, which exceeds pericellular inhibitor concentrations in vivo by nearly 3 orders of magnitude. Diffusion analysis predicts obligate catalytic activity (excess of local enzyme over inhibitor concentration) that extends to 1.33 microns from the site of granule extrusion (7.8-fold larger than the mean radius of the granule), with a duration of 12.4 ms, when the pericellular concentration of alpha 1-antitrypsin equals that of normal plasma. In contrast, when PMN are bathed in alpha 1-antitrypsin concentrations found in plasma from individuals with alpha 1-antitrypsin deficiency, the radius and duration of obligate catalytic activity are increased 2.5-fold and 6.2-fold, respectively. These simulations agree remarkably well with our recent direct observations and provide a novel, nonoxidative mechanism by which quantum bursts of extracellular proteolytic activity occur despite proteinase inhibitors in the bathing medium. Titration of local enzyme-inhibitor concentration is the dominant determinant of the size and duration of such events. This construct provides new insights into the pathogenesis of tissue injury in alpha 1-antitrypsin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519775 TI - Kinetically trapped structure in the renaturation of reduced oxindolealanine 62 lysozyme. AB - The refolded products of reduced native lysozyme and reduced OX62 lysozyme, in which Trp62 is converted to oxindolealanine (OX62) during the renaturation of sulfhydryl-disulfide interchange reactions at pH 8 and 37 degrees C, were investigated. On gel-chromatography eluted with 10% aqueous acetic acid containing 4 M urea, two peaks appeared in the refolded product of reduced OX62 lysozyme while a single peak appeared in the refolded product of reduced native lysozyme. From the analyses of the activity and primary and the tertiary structures of the derivative, the structure of the derivative from reduced native lysozyme was confirmed to be identical to that of the untreated one. On the other hand, the refolded product from reduced OX62 lysozyme had the same primary structure but a different tertiary structure compared to the untreated one. The tertiary structure of the refolded product from the reduced OX62 lysozyme was changed to that of the untreated one by the denaturation-renaturation treatment under nonreduced conditions. However, the refolded species was barely changed to that of the untreated one by incubation under physiological conditions. Therefore, the refolded product from reduced OX62 lysozyme was suggested to be a metastable and kinetically trapped product in the renaturation process of reduced OX62 lysozyme. In addition, an interaction involving the folding process of reduced lysozyme was discussed on the basis of the NMR analyses of the metastable structure. PMID- 8519776 TI - Proton-translocating carboxyl of subunit c of F1Fo H(+)-ATP synthase: the unique environment suggested by the pKa determined by 1H NMR. AB - Subunit c of the H(+)-transporting F1Fo ATP synthase (EC 3.6.1.34) is thought to fold across the membrane as a hairpin of two alpha helices with a conserved Asp/Glu residue, centered in the second membrane-spanning helix, which is thought to function in H+ translocation. NMR studies indicate that the purified subunit c from Escherichia coli is also folded as a hairpin in a chloroform/methanol/H2O (4:4:1) solvent mixture [Girvin, M. E., & Fillingame, R. H. (1993) Biochemistry 32, 12167-12177] and that the conserved Asp remains uniquely reactive in this solvent mixture [Girvin, M. E., & Fillingame, R. H. (1994) Biochemistry 33, 665 674]. The pKa of Asp61 is of interest because of its unique reactivity and because it is thought to protonate and deprotonate during each proton translocation cycle. We have determined the pKa value of the carboxyl group of the functional Asp in wild type and two functional, mutant subunit c proteins, i.e. the Ala24-->Asp (D24D61) and the Ala24-->Asp/Asp61-->Asn (D24N61) mutant proteins. The pKa values were determined by 1H NMR spectroscopy by measuring changes in the alpha and beta proton chemical shifts by constant time two dimensional (2D) correlated spectroscopy. The pKa of Asp61 in the purified wild type protein was 7.1. This pKa was significantly higher than the pKa of the other two Asp residues, i.e. Asp7 and Asp44 which were 5.4 and 5.6, respectively. The pKa of the two Glu residues in the protein were determined by 2D total correlation spectroscopy and found to be approximately 5.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519777 TI - Mechanism of Agrobacterium beta-glucosidase: kinetic analysis of the role of noncovalent enzyme/substrate interactions. AB - The role of noncovalent interactions in the catalytic mechanism of the Agrobacterium faecalis beta-glucosidase was investigated by steady-state and pre steady state kinetic analysis of the hydrolysis of a series of monosubstituted aryl glycosides, in which the hydroxyl groups on the glycone were substituted by hydrogen or fluorine. Contributions of each hydroxyl group to binding of these substrates at the ground state are relatively weak (interaction energies of 3.3 kJ/mol or smaller) but are much greater at the two transition states (glycosylation and deglycosylation). The strongest transition state interactions were at the 2 position (at least 18 and 22 kJ/mol for glycosylation and deglycosylation, respectively) with the interactions at the 3 and 6 positions contributing at least another 9 kJ/mol of binding energy at both transition states. The interaction at the 4 position is less crucial to transition state binding but important for stabilization of the glycosyl-enzyme intermediate. Comparison of observed rates with those for spontaneous hydrolysis of the same substrates provides evidence for oxocarbenium ion character at both transition states, that for deglycosylation apparently having the greater positive charge development at the anomeric center. PMID- 8519778 TI - Kinetic analysis of cAMP-dependent protein kinase: mutations at histidine 87 affect peptide binding and pH dependence. AB - Mutation of His87 in the catalytic (C-) subunit of the cAMP-dependent protein kinase (cAPK) led to changes in the kinetic properties of this enzyme. The C subunit is a bilobal structure, with catalysis occurring in the cleft between the two lobes. His87 lies at the edge of the cleft, making an interaction with phosphothreonine, 197. This is the only direct electrostatic or hydrogen-bonding interaction between the small and large lobes. Solvent viscosity studies of the His87Ala mutant of the C-subunit (rC[H87A]) revealed that binding of two peptides, LRRASLG and LRRASLG-NH2, was impaired relative to that of the wild-type C-subunit. Consistent with this, the Ki's for two inhibitor peptides, LRRAALG and LRRAALG-NH2, were 4 and 1.4 mM, respectively, 5- and 7-fold higher than the Ki's of the respective peptides for wild-type protein. Kinetic constants for three octapeptide substrates that differed only at the P+2 position suggested a direct interaction of His87 with residues at this site. The kcat for rC[H87A] was 2-3 fold higher than kcat for the wild-type enzyme, indicating an effect of the mutation on the rate-limiting step, product release. The pH dependence of kinetic parameters for rC[H87A] was also measured. A single pKa of 6.5 was observed in kcat/Kpeptide as compared to the two pKa's of 6.5 and 8.5 for the wild-type enzyme. These changes suggest a role for His87 in substrate recognition and in stabilization of the catalytically competent conformation of the enzyme. PMID- 8519779 TI - Structures of oligosaccharide-bound forms of the endoglucanase V from Humicola insolens at 1.9 A resolution. AB - Cellulose, a polymer of beta-1,4-linked glucose residues, is the major polysaccharide component of plant cell walls and the most abundant biopolymer. The underlying mechanisms of the enzymatic degradation of cellulose are of increasing commercial and ecological significance. Endoglucanase V, from the cellulolytic soil hyphomycete Humicola insolens, is an endocellulase, the catalytic core of which consists of 210 amino acids and is known to hydrolyze the beta-1,4 links with inversion of configuration at the anomeric carbon. The major products of cellulose hydrolysis are cellobiose and cellotriose. The crystal structures of the endoglucanase V (EGV) from H. insolens, in native, product (cellobiose), inactive mutant (D10N), and oligosaccharide-bound [(D10N) cellohexaose] forms, have been determined at resolutions of 1.9 A or better. EGV consists of a six-stranded beta-barrel domain with long interconnecting loops. A 40 A groove exists along the surface of the enzyme, and this contains the catalytic residues, Asp 10 and Asp 121. The two catalytic aspartates sit to either side of the substrate binding groove in an ideal conformation for facilitating cleavage by inversion, their carboxyl groups being separated by approximately 8.5 A. The complex between substrate and inactive mutant reveals excellent density for an oligosaccharide in six of the enzyme's seven substrate binding subsites. No sugar moiety, however, is seen bound to the -1 subsite at the point of cleavage. The geometry of the cleavage site suggests that the enzyme would favor the binding of sugars with an elongated glycosidic bond, as found in the transition state, as opposed to the binding of substrate. The oligosaccharide complexes reveal solvent water suitably placed for participation in a single displacement reaction as first suggested by Koshland in 1953 [Koshland, D. E. (1953) Biol. Rev. 28, 416-436]. A large conformational change takes place upon substrate binding. This "lid flipping" has the effect of increasing the hydrophobic environment of the catalytic proton donor, enclosing the active site at the point of cleavage, and bringing a third aspartate (Asp 114) in close proximity to the substrate. Site-directed mutagenesis of the catalytic residues has been used to confirm their significance in catalysis. PMID- 8519780 TI - Proposed mechanism for the cytochrome P450-catalyzed conversion of aldehydes to hydrocarbons in the house fly, Musca domestica. AB - Experiments were performed to elucidate the mechanism of hydrocarbon formation in microsomal preparations from the house fly, Musca domestica. Antibody to both house fly cytochrome P450 reductase and a purified cytochrome P450 (CYP6A1) from the house fly inhibited (Z)-9-tricosene (Z9-23:Hy) formation from [15,16-3H]-(Z) 15-tetracosenal (24:1 aldehyde). Chemical ionization-gas chromatography-mass spectrometry (CI-GC-MS) analyses of the n-tricosane formed by microsomal preparations from [2,2-2H2,2-13C]- and [3,3-2H2,3-13C]tetracosanoyl-CoA demonstrated that the deuteriums on the 2,2- and 3,3-positions were retained in the conversion to the hydrocarbon product. Likewise, CI-GC-MS analysis of the Z9 23:Hy formed from [1-2H]tetracosenal by microsomal preparations demonstrated that the aldehydic proton on the 1-carbon was transferred to the hydrocarbon product. Hydrogen peroxide, cumene hydroperoxide, and iodosobenzene were able to support hydrocarbon production from [3H]24:1 aldehyde in place of O2 and NADPH for short incubation times. From these data, a cytochrome P450 mechanism is proposed in which the perferryl iron-oxene, resulting from heterolytic cleavage of the O-O bond of the iron-peroxy intermediate, abstracts an electron from the C=O double bond of the carbonyl group of the aldehyde. The reduced perferryl attacks the 1 carbon of the aldehyde to form a thiyl-iron-hemiacetal diradical. The latter intermediate can fragment to form an alkyl radical and a thiyl-iron-formyl radical. The alkyl radical then abstracts the formyl hydrogen to produce the hydrocarbon and CO2. PMID- 8519782 TI - Adolescent health-threatening and health-enhancing behaviors: a study of word association and imagery. AB - PURPOSE: To examine the ways in which perceived risks and benefits relate to health-threatening and health-enhancing behaviors by adolescents. METHOD: The study used a word association methodology to explore adolescents' thoughts and affective feelings associated with five health-threatening behaviors (e.g., drinking beer, smoking cigarettes) and three health-enhancing behaviors (e.g., exercising, using a seat belt). RESULTS: Each behavior elicited a mix of positive and negative associations. Health-threatening behaviors had many positive associations in common, such as having fun, social facilitation, and physiological arousal. Health-enhancing behaviors had much less commonality in their positive associations. Patterns of negative associations were not highly similar across behaviors. The content and affective tone of the associations were closely linked to participation in health-threatening behaviors and health enhancing behaviors. Participants in an activity were far more likely than nonparticipants to associate that activity with positive outcomes, concepts, and affect and less likely to produce outcomes, concepts, and affect and less likely to produce negative associations. CONCLUSIONS: The word association methodology provides a useful technique for exploring adolescents' cognitions and affective reactions with regard to health-related behaviors. The data provided by this method have implications for prevention and intervention programs, as well as for future research. PMID- 8519781 TI - The pleckstrin homology domain of phospholipase C-delta 1 binds with high affinity to phosphatidylinositol 4,5-bisphosphate in bilayer membranes. AB - The pleckstrin homology (PH) domain of phospholipase C-delta 1 (PLC-delta 1) binds to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in phospholipid membranes with an affinity (Ka approximately 10(6) M-1) and specificity comparable to those of the native enzyme. PLC-delta 1 and its PH domain also bind inositol 1,4,5-trisphosphate, the polar head group of PI(4,5)P2, with comparable affinity and approximately 1:1 stoichiometry. A peptide corresponding to amino acids 30-43 of the PLC-delta 1 PH domain contains several basic residues predicted to bind PI(4,5)P2, but binds weakly and with little specificity for PI(4,5)P2; hence the tertiary structure of the isolated PH domain is required for high affinity PI(4,5)P2 binding. Our PI-(4,5)P2 binding results support the hypothesis that the intact PH domain, serving as a specific tether, directs PLC delta 1 to membranes enriched in PI(4,5)P2 and permits the active site, located elsewhere in the protein, to hydrolyze multiple substrate molecules before this enzyme dissociates from the membrane surface. PMID- 8519783 TI - Dieting and "watching" behaviors among adolescent females: report of a multimethod study. AB - PURPOSE: This study posits a distinction between "watching what you eat" and dieting behaviors in a sample of adolescent females. Findings suggest that the dichotomy of dieter/nondieter fails to capture a range of healthful behaviors practiced by many adolescent girls. METHODS: Anthropologic and nutritional research methods were used in this study. Data were drawn from 1 year of a longitudinal study of food intake and dieting behaviors in a sample of 231 adolescent females. Multiple methods including one ethnographic interview, a survey questionnaire, a telephone interview, and food records were collected from each informant. RESULTS: Although 44% of the girls in this sample reported trying to lose weight on the day of the survey, only 8.6% of the food records reflected dieting days. In interviews, many identified "watching what they eat" as a health promoting strategy that allowed them to maintain their weight. Analysis of food record data confirmed a trend toward higher intakes of micronutrients. CONCLUSIONS: Research concerned with adolescent weight loss behaviors has focused more on negative than positive health attitudes and behaviors. The present study identified the behavior of "watching" as distinct from dieting. "Watching" was widely utilized by girls in this sample as a way to maintain weight and promote health. PMID- 8519784 TI - Durations of adolescent sexual relationships before and after conception. AB - PURPOSE: To explore durations of young couples' relationships between meeting and first intercourse, before first conception and for two years following conception and the associations between these durations; to describe the association between these durations and the young women's perceptions of the nature of these relationships. METHODS: Three hundred and seven adolescent women were enrolled in a prospective study while presenting for pregnancy tests (the index event); they were followed for two years in three groups--those with negative tests, those who terminated the pregnancy and those who bore a child. Retrospective information about durations of relationships with first partners and partners at the index event was obtained at baseline; follow-up data was obtained on continuing relationships with the index partner. RESULTS: Durations of relationships between adolescent females and their partners in this sample, both before and after conception, are rarely brief; the median duration of a girl's prior relationship with a partner with whom she conceives is almost two years. Similarly, almost half of the sample is still in a relationship at two years following the index event, a proportion that rises to two-thirds among those who bore a child together. CONCLUSIONS: Contrary to common belief or practice, there may be sufficient time and commitment to include many male partners in intervention programs before, and in parenting programs after, a first conception--a practice which could have positive implications for both adolescent partners and, potentially, for their child. PMID- 8519785 TI - Prevalence of HIV-related risk behaviors and STDs among incarcerated adolescents. AB - PURPOSE: To determine the HIV-related risk behaviors and STDs in a population of incarcerated adolescents in order to strategically target education and prevention efforts. METHODS: A single point-in-time prevalence study based on an analysis of intake medical records of 1,215 incarcerated youth were analyzed for HIV risk behaviors and STD history. RESULTS: Incarcerated adolescents report high rates of risk behaviors for HIV infection and STDs, with 75% reporting three or more sex partners, 25% never using condoms and 19% having a current diagnosis of at least one STD. Significantly more females than males reported a history of STDs and had higher rates of current diagnoses of chlamydia/non-gonococcal urethritis, trichomonas and gonorrhea. CONCLUSIONS: Ethnic/racial and gender differences were found in risk behaviors for STDs among a sample of incarcerated adolescents. PMID- 8519786 TI - A pilot program of contraceptive continuation in six school-based clinics. AB - PURPOSE: Few school-based health centers (SBHC) in the United States dispense contraceptives on-site and little is known about contraceptive continuation in these health centers. METHODS: An 11-month contraceptive continuation pilot project offering monthly reproductive health assessment and counseling to students enrolled in Baltimore school clinics was evaluated. One hundred-forty three women voluntarily enrolled in the study over a seven month period. A monthly contraceptive calendar was developed to collect data on contraceptive use, pregnancy and STD risk, sexual behavior and parental support for contraceptive use. Physical assessment was provided as needed to assess the presence of STD's or pregnancy. Data were analyzed for the month prior to enrollment in the program and eleven months after entry into the program. RESULTS: Both contraceptive (OCP) use and abstinence increased over the course of the program. Condom use remained at approximately 30% with frequent use of OCP's and condoms, condoms or abstinence. Program drop-out was common. Thirteen students became pregnant while enrolled in the program and 35% of the students were diagnosed with one or more sexually transmitted diseases. Partner-switching was common, although two or more partners within any one month was rare. CONCLUSIONS: Monthly follow-up provided through SBHCs can improve contraceptive use although dropout rate and contraceptive failure remain high. PMID- 8519787 TI - The benefits of school-based condom availability: cross-sectional analysis of a comprehensive high school-based program. AB - OBJECTIVES: To analyze the benefits of a school-based condom availability program relative to the risks that such a program may incur. METHODS: A confidentially administered survey instrument was completed by 152 randomly selected high-school students (approximately 14% of the entire student population). RESULTS: The respondents had a mean age of 15.9 years (range: 14-19 years) and a proportionate gender distribution. Ninety-three percent of all respondents had "heard of" the school's program and knew from whom they could receive condoms. Twenty-six percent of the respondents had received condoms from the program with 67% using them. Of those receiving condoms but not using them, more than half did not need them, owing to absence of anticipated sexual activity. Of the nonreceivers, 53% had never had sexual intercourse and 27% received condoms from other sources. The benefit of the program by aiding a sexually-active student was found to be more than three times as great as the risk of encouraging a nonsexually active student to have sexual intercourse (RR = 3.2; 95% C.I. = 2.1, 4.9). The prevalence of sexual activity among all respondents was not significantly higher than the state's average based on gender and age (59.8% vs. 54.5%; z = 1.24, p > .05, n.s.). CONCLUSION: Given the lack of increased sexual activity and the favorable benefit-risk ratio, we conclude that school-based condom availability is successfully utilized by sexually-active adolescents and may be an effective means to reduce potentially harmful outcomes, such as unintended pregnancy and sexually-transmitted diseases. PMID- 8519788 TI - Antithrombin III deficiency, deep venous thrombosis, and oral contraceptive use. PMID- 8519789 TI - Follow-up of pregnant teens at a hospital-based clinic. AB - PURPOSE: Our study investigates the factors associated with length of time to referral appointments for pregnant teens diagnosed in a hospital-based adolescent clinic. METHODS: Ninety-six pregnancies diagnosed during a six-month period at a hospital-based adolescent clinic were followed prospectively. Demographic data, plans for pregnancy, last menstrual period (LMP), and who accompanied patient to the appointment were recorded by providers. Appointment at referral site was confirmed by the patients' primary provider, contact with the patient, and/or referral site. The time from first positive pregnancy test to kept referral appointment was determined. RESULTS: Of the 96 diagnosed pregnancies, data were available for 94 patients. The mean age was 17.6 +/- 2.0 years. The average gestation was 7.4 +/- 4.2 weeks (range 4-27 weeks) at initial visit and 11.7 +/- 4.9 weeks (5-30 weeks) at referral site. The time to referral appointment was significantly shorter for patients who planned to terminate compared with those who planned to continue with the pregnancy (22.4 +/- 16.6 vs. 35.7 +/- 24.5 days, P = 0.0042). However, the final decision to continue vs. terminate the pregnancy was a stronger predictor of the interval to kept referral appointment (R2 = 0.177) than the initial plan. Those who planned to tell more people about their pregnancy had a significantly higher rate of continuing the pregnancy than those terminating. CONCLUSION: Pregnant teens may need multiple follow-up appointments to facilitate connection to referral care. Close follow-up and communication with referral sites needed to optimize care of pregnant teens because of the delay until teens access pregnancy services. PMID- 8519790 TI - Adolescent health research as we proceed into the twenty-first century. PMID- 8519791 TI - Mg- and Ca-actin filaments appear virtually identical in steady-state as determined by dynamic light scattering. AB - Dynamic light scattering measurements show that although Mg-actin polymerizes more rapidly than Ca-actin (actin at 0.04-0.4 mg/ml polymerized with 0.1 M KCl +/ 2 mM MgCl2 or CaCl2, at room temperature or at 10 degrees C), steady-state filaments exhibit nearly identical intensity autocorrelation functions and similar mean scattered intensities. The dynamic data are used to measure the persistence length of the filaments which is found to be 4.2 microns independent of the bound cation and of the actin concentration. PMID- 8519792 TI - The reaction of chicken liver sulfite oxidase with dimethylsulfite. AB - We have undertaken a steady-state and rapid kinetic study of the reaction of enzyme with sulfite and dimethylsulfite. Methylation of sulfite results in a significant increase in Km and Kd for the substrate in the course of steady-state and rapid reaction kinetics, respectively, but kcat and the limiting rate constant for enzyme reduction (kred) are essentially unchanged. This indicates that while substrate oxyanion groups are effective in stabilizing the Eox.S complex, the breakdown of this complex proceeds at the same rate even in their absence. The critical element of the substrate required for reactivity is a suitable lone-pair available to undertake nucleophilic attack on a Mo = O group of the active site. PMID- 8519793 TI - Clinical isolates of HIV-1 contain few pre-existing proteinase inhibitor resistance-conferring mutations. AB - Proteinase inhibitors are an important new class of antiviral agents for AIDS, however, in vitro experiments have identified proteinase mutations that confer resistance to several different families of the inhibitors. This study was undertaken to determine if these resistance-conferring amino-acid substitutions occur in HIV strains before the application of selective pressure. We determined the nucleic acid sequence of the proteinase gene from the 23 clinical isolates of HIV-1 and three laboratory-adapted strains using a method that detects the majority species present in viral populations. Analysis of minor subpopulations will require alternative strategies. The clinical isolates studied contained an average of 3 (range 1-8) amino-acid substitutions as compared to the prototypical BH10 sequence. We did not detect substitutions characteristic of reported highly proteinase-resistant strains. These results suggest significant variation occurs in the HIV-1 proteinase gene but pre-existing highly proteinase-resistant strains are uncommon. PMID- 8519794 TI - Molecular cloning and nucleotide sequence of the 1,2-alpha-D-mannosidase gene, msdS, from Aspergillus saitoi and expression of the gene in yeast cells. AB - A full-length cDNA encoding 1,2-alpha-D-mannosidase (EC 3.2.1.113) from Aspergillus saitoi was cloned. Analysis of the 1718 bp nucleotide sequence of the cDNA revealed a single open reading frame with 1539 nucleotides of 1,2-alpha-D mannosidase gene, msdS. The predicted amino-acid sequence of 1,2-alpha-D mannosidase consists of 513 residues with a molecular mass of 55,767 and is 70%, 26% and 35% identity with those of Penicillium citrinum 1,2-alpha-D-mannosidase, yeast alpha-mannosidase, and mouse alpha-mannosidase. The cDNA of the msdS gene has been cloned and expressed in yeast cells. To identify the activity of expression product methyl-2-O-alpha-mannopyranosyl-alpha-mannopyranoside (Man alpha 1-->2Man-OMe) was used as a substrate at pH 5.0. PMID- 8519795 TI - A new human guanylate cyclase-activating peptide (GCAP-II, uroguanylin): precursor cDNA and colonic expression. AB - We have amplified, cloned, and sequenced 583 bp GCAP-II/uroguanylin-specific cDNA from human colon cDNA first strand. The cDNA codes for a putative 112 amino-acid precursor protein including the sequence of uroguanylin and GCAP-II. Northern blot hybridization revealed a high level expression of the GCAP-II gene in human colon, but not in the kidney. This expression of GCAP-II indicates a pivotal role in cGMP-mediated functions of the colon. PMID- 8519796 TI - Inactivation precedes overall molecular conformation changes during enzyme denaturation. PMID- 8519797 TI - Dimer structure as a minimum cooperative subunit of small heat-shock proteins. AB - Recently, it has been shown that small heat-shock proteins (Hsp25, Hsp27) are molecular chaperones. They bind to thermally unfolded proteins and can also assist refolding of denatured proteins. Mammalian small Hsps can form oligomeric structures of about 32 subunits. Until now, no data about cooperativity and stability of the interactions between the subunits of sHsps are available. To analyze these interactions we studied mouse Hsp25 and human Hsp27 by difference adiabatic scanning microcalorimetry (DASM) and circular dichroism (CD). Here we show that, according to DASM data, the minimum cooperatively melting structure is a sHsp-dimer. CD data indicate that Hsp25 major secondary structure, the beta pleated conformation, is resistant to acidic influence up to pH 4.5 and, at neutral pH values, to heat treatment up to 60 degrees C. The melting pattern of Hsp25/27 bears resemblance to alpha-crystallins. CD data indicate similar secondary, tertiary and quaternary structures of the proteins compared. This finding is in agreement with the revealed homology of primary structure of these proteins and their common chaperone function. PMID- 8519798 TI - Completion of the thioredoxin reaction mechanism: kinetic evidence for protein complexes between thioredoxin and fructose 1,6-bisphosphatase. AB - The activation of chloroplast fructose 1,6-bisphosphatase from spinach and soybean leaves by the two chloroplast thioredoxins isolated from the same plants has been studied. The thioredoxin saturation characteristics (Vmax: 0.15-103.2 mumol Pi/min per mg enzyme; K0.5: 0.0048-0.84 microM; Hill coefficient n: 1.02 3.80) indicate that in addition to the reductive activation by thioredoxin specific complex formation between thioredoxin and fructose 1,6-bisphosphatase is responsible for fine regulation of the enzyme activity. This complex formation has been inserted into the thioredoxin mechanism and the physiological consequences discussed. Obviously, physiologically relevant investigations of the thioredoxin-dependent regulation of fructose 1,6-bisphosphatase activity can only be performed in homologous enzyme-thioredoxin combinations. Dithiothreitol and E. coli thioredoxin are no complete substitutes in regulatory studies. PMID- 8519799 TI - Effects of substrate binding and pH on the secondary structure of carnitine acetyltransferase. AB - Carnitine acetyltransferase (CAT) exists as a monomer in solution as demonstrated by dynamic light scattering measurements. Under these conditions, interactions between CAT and its substrates, L-carnitine and acetyl-CoA, were studied by circular dichroism (CD) and fluorescence spectroscopy over a wide range of substrate concentrations. CD data indicated that the binding of L-carnitine and acetyl-CoA caused changes in the secondary structure of the protein. Quenching of the intrinsic protein fluorescence upon binding of either substrate corroborated these findings. Analysis of the binding data suggests that binding of both substrates to CAT is specific and saturable, and that there is a single binding site (or multiple identical and independent binding sites) on CAT for each substrate. Estimated L-carnitine/CAT dissociation constants were 506 +/- 58 microM and 236 +/- 27 microM in the absence or presence of acetyl-CoA, respectively. The dissociation constant for acetyl-CoA/CAT was estimated at 19 +/ 7 microM. The effect of pH on the secondary structure of the protein was determined in order to investigate the structural cause for the pH-dependent enzymatic activity of CAT. Loss of alpha-helices and a reduction of thermal stability in CAT was detected at both acidic and basic pH. Thus, the reduced catalytic activity of CAT at acidic or basic pH may be due to pH-induced protein unfolding. PMID- 8519800 TI - Occurrence and purification of the photoactive yellow protein of Ectothiorhodospira halophila (PYP) and of immunologically related proteins of Rhodospirillum salexigens and Chromatium salexigens and intracellular localization of PYP. AB - The photoactive yellow protein of Ectothiohodospira halophila (PYP) was purified to homogeneity by an advanced method and applied as an affinity ligand for the isolation of an anti-PYP IgG fraction which was used for immunoscreening. The distribution of proteins immunologically related to PYP was investigated in protein fractions of 51 strains from 38 species of non-halophilic and halophilic phototrophic and chemotrophic eubacteria and archaeobacteria. Strong immunoreactive bands indicating the presence of authentic PYP on Western blots (apparent mass 17.8 kDa) was only found in the strains of E. halophila. Additionally, two soluble proteins of Chromatium salexigens and Rhodospirillum salexigens (apparent molecular masses 16.4 and 19 kDa, respectively) cross reacted to approx. 6% and 4%. Analyses of cell fractions of E. halophila revealed that PYP is a cytoplasmic protein. PMID- 8519801 TI - Inhibition of pig kidney diamine oxidase by nazlinin and nazlinin derivatives. AB - Nazlinin (1-(4-butylamino)-1,2,3,4-tetrahydro-beta-carboline) (1), an alkaloid recently isolated from Nitraria schoberi, and its two derivatives, 1-(4 butylamino)-3,4-dihydro-beta-carboline (2) and 1-(4-butylamino)-beta-carboline (3), were synthesized and their interaction with pig kidney diamine oxidase (PKDO) was studied. Nazlinin appeared to be a very poor substrate while 3 was a good substrate with an apparent Km of 9.3-10(-5) M. The enzyme was inhibited by 1 and 2. With both compounds the mode of inhibition found was non-competitive and inhibition constants calculated from the slopes and intercepts of double reciprocal plots show that 2 is a much more potent inhibitor than the natural product. The relationship between the structure of these compounds and the results found is discussed. PMID- 8519802 TI - The characterization of two aminopeptidase activities from the cyanobacterium Anabaena flos-aquae. AB - Aminopeptidase activity, indicated by hydrolysis of the synthetic substrate alanine p-nitroanilide, was identified in the cyanobacterium Anabaena flos-aquae. On purification, 2 enzymes were separated by gel filtration chromatography, a 188 kDa multimer (AP-I) and a 59 kDa monomeric metalloprotein (AP-II). Their activities against a range of alanine-containing peptides were screened. Both enzymes were capable of removing a variety of N-terminal residues, including proline. Neither removed N-terminal acidic residues. The activity of AP-I appeared to be limited to di- and tri-peptides, while AP-II was capable of hydrolysing (Ala)5. It was not possible to assign the active-site chemistry of AP I to one of the known hydrolase subgroups as none of the potential inhibitors tested had a significant inhibitory effect. This is the first reported purification of aminopeptidases from a cyanobacterium. PMID- 8519803 TI - Analysis of the active site and activation mechanism of the Leishmania surface metalloproteinase GP63. AB - The major surface glycoprotein of Leishmania promastigotes, referred to as GP63, is a zinc metalloproteinase of 63,000 M(r) containing a glycosylphosphatidylinositol (GPI) membrane anchor. Recent studies demonstrated that recombinant GP63 (rGP63) expressed by the baculovirus insect cell system was secreted as a glycosylated latent proteinase that required activation for full proteinase activity (Button et al. (1993) Gene 134, 75-81). To extend these studies, the active site of L. major GP63 was characterized by site-directed mutagenesis and the activation mechanism of latent rGP63 was studied using both secreted and cell surface expression systems. To determine whether the proposed active site of L. major GP63 conforms to other well characterized zinc metalloproteinases, the proposed GP63 catalytic Glu-265, corresponding to catalytic Glu-147 of thermolysin, was changed to Asp-265. Using a transient expression system in COS-7 cells, expression of the Asp-265 mutant GP63 gene resulted in rGP63 with no detectable proteinase activity, whereas expression of the wild-type GP63 gene resulted in rGP63 with a level of proteinase activity similar to native GP63. Thus, the mechanism of GP63 proteinase activity is predicted to be homologous to that of other well characterized zinc metalloproteinases. NH2-Terminal sequence analysis revealed that activation with HgCl2 resulted in removal of the pro region, ultimately generating the mature NH2 terminus. This processing included the removal of a conserved Cys residue (Cys 48) and occurred by a cis mechanism, since the addition of previously activated rGP63 did not lead to an enhancement of latent rGP63 proteinase activation. The mechanism of activation of GP63 is consistent with the cysteine switch mechanism proposed for matrix metalloproteinases and thus has been conserved from protozoa to mammals. PMID- 8519804 TI - Functional analysis of E. coli threonine dehydrogenase by means of mutant isolation and characterization. AB - The oxidation of L-threonine to 2-amino-ketobutyrate, as catalyzed by L-threonine dehydrogenase, is the first step in the major pathway for threonine catabolism in both eukaryotes and prokaryotes. Threonine dehydrogenase of E. coli has considerable amino-acid sequence homology with a number of Zn(2+)-containing, medium-chain alcohol dehydrogenases. In order to further explore structure/function interrelationships of E. coli threonine dehydrogenase, 35 alleles of tdh that imparted a no-growth or slow-growth phenotype on appropriate indicator media were isolated after mutagenesis with hydroxylamine. Within this collection, 14 mutants had single amino-acid changes that were divided into 4 groups: (a) amino-acid changes associated with proposed ligands to Zn2+; (b) a substitution of one of several conserved glycine residues; (c) mutations at the substrate or coenzyme binding site; (d) alterations that resulted in a change of charge near the active site. These findings uncover previously unidentified amino acid residues that are important for threonine dehydrogenase catalysis and also indicate that the three-dimensional structure of tetrameric E. coli threonine dehydrogenase has considerable similarity with the dimeric horse liver alcohol dehydrogenase. PMID- 8519805 TI - MCD, EPR and NMR spectroscopic studies of rabbit hemopexin and its heme binding domain. AB - Heme binding to rabbit hemopexin and its domain I, obtained by proteolytic cleavage of intact hemopexin, was studied by EPR, MCD and 1H-NMR spectroscopies. The data obtained support the proposal that the heme Fe(III) is coordinated by two histidine ligands (Morgan et al. (1988) J. Biol. Chem. 263, 8220-8225; Muster et al. (1991) J. Protein Chem. 10, 123-128) and are inconsistent with recently reported mutagenesis studies indicating that bis-histidine ligation is unlikely (Satoh et al. (1994) Proc. Natl. Acad. Sci. USA 91, 8423-8427). Although the MCD data are consistent with both bis-histidine and histidine/lysine ligation, the EPR spectra are typical of bis-histidine ligation. Overall the magneto-optical spectra are characteristic for bis-histidine ligation. The EPR and NMR data indicate that there is a difference in the heme environments of the intact hemopexin and its domain I but overall the spectroscopic information suggests heme bound to domain I has the same ligands as intact hemopexin. The 1H-NMR studies indicate that heme binding to domain I perturbs at least 4 of the 5 histidines. This is consistent with axial ligation of the heme by two histidines, and a conformational change induced by heme binding affecting two more. Interestingly, resonances of the carbohydrate bound to intact hemopexin and domain I were also perturbed by heme binding. pH dependence studies showed that heme remained bound to intact hemopexin over the pH range 6.5-10.0 without any major change in the ligation or environment of the heme. PMID- 8519806 TI - Purification and characterization of a new serine proteinase from Bacillus subtilis with specificity for amino acids at P1 and P2 positions. AB - A proteinase was purified 230-fold to apparent homogeneity from culture filtrates of Bacillus subtilis by a series of column chromatographies on DE52, DEAE Toyopearl, Cellulofine GC200M, and Mono-Q, using Boc-Ala-Ala-Pro-Ser-pNA as a substrate. The molecular weight of the proteinase was estimated to be 42,000 by SDS-PAGE in the presence of 2-mercaptoethanol. Studies on the substrate specificity with peptide p-nitroanilides and natural peptides revealed that this proteinase preferentially hydrolyzed the peptide bond on the carboxyl-terminal side of either serine or alanine residues at the P1 position and hydrophobic bulky amino acids at P2. It was most active at pH 9.5 for the hydrolysis of Boc Ala-Ala-Pro-Ser-pNA. The enzyme was inactivated by diisopropyl fluorophosphate (DFP), but not by tosyl-L-phenylalanine chloromethylketone (TPCK) or by EDTA. Based on the reactivity toward substrates and inhibitors, this enzyme differs from elastase- or subtilisin-like proteinase, hence it is a new type of proteinase with specificity for amino acids at P1 and P2 positions. PMID- 8519807 TI - Alterations in gene expression and signal transductions in human melanocytes and melanoma cells. AB - The development of techniques to cultivate human primary melanocytes in vitro has provided the technical foundation for understanding the biology of this cell. Human melanocytes require various growth factors and agents for proliferation in vitro. These compounds activate two major signal transduction pathways: a calcium and phospholipid-dependent (protein kinase C or PKC) pathway and a cyclic AMP (cAMP)-dependent (protein kinase A or PKA) pathway. Alterations in these signal transduction pathways coupled with changes in specific genes (protooncogenes, growth factors, and tumor suppressor genes) have been observed in human melanoma cells compared with normal melanocytes. Our own work indicates that loss in the expression of the PKC beta II isotype is a common, if not universal, alteration that occurs early in human melanocyte transformation. In this review, we concentrate on alterations in the signal transduction pathways in human melanocytes and melanoma cells and delineate how an understanding of these changes may allow us to understand the molecular mechanisms involved in human melanocyte transformation. PMID- 8519808 TI - Tumor metastasis to brain: role of endothelial cells, neurotrophins, and paracrine growth factors. AB - An important clinical endpoint in patients with cancer is formation of metastases in the brain. Understanding this phenomenon is important in several types of malignancies, including melanoma, lung and breast cancers. Metastatic tumor cells use specific adhesion molecules to home to brain, and there they must attach to microvessel endothelial cells and respond to brain endothelial cell-derived motility factors and brain invasion factors to invade the CNS. Neurotrophins are important invasion factors in this process, and the ability to invade into the brain may well depend on metastatic cell responses to neurotrophins and production of basement membrane-degradative enzymes capable of locally destroying the blood-brain barrier. Brain-metastatic human melanoma cells express low affinity p75 receptor for neurotrophins such as nerve growth factor, but they do not express the high-affinity-type receptors for nerve growth factor encoded by the protooncogene trkA. Tumor cells can proliferate in the CNS in response to local paracrine growth factors and inhibitors, but their growth also depends on their producing and responding to autocrine growth factors. A major organ-derived (paracrine) growth factor has been isolated that differentially stimulates the growth of cells metastatic to the brain. Characterization of this mitogen demonstrated that it is a transferrin-like glycoprotein; cells that are metastatic to brain express greater numbers of transferrin receptors on their surfaces than cells that are poorly metastatic or metastatic to other sites. Transferrin-like factors are expressed in fetal brain and could represent the transferrin-like factors that stimulate growth of brain-metastatic melanoma and breast cancer cells. These and other factors are probably important in determining whether metastatic cells can successfully invade, colonize, and grow in the CNS. PMID- 8519809 TI - Hodgkin's disease: a cytokine-producing tumor--a review. AB - Cytokines and hematopoietic growth factors are actively involved in regulation of proliferation, differentiation, and cellular functions of various cell lineages. Each cytokine exhibits pleiotropic biological functions on different target cells and subfamilies of cytokines often have redundant biological effects on the same target cell. Hodgkin's disease represents one of the most common human lymphoma entities, the molecular pathogenesis of which is not well understood. Hodgkin's disease is characterized by the presence of typical, presumed malignant Hodgkin and Reed-Sternberg cells in a hyperplastic background of normal reactive lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils, and stromal cells. The histopathological presentation and characteristic clinical features of Hodgkin's disease correlate with an unbalanced production of multiple cytokines. Hodgkin and Reed-Sternberg cells express mRNA and proteins of various cytokines, growth factors, and cytokine receptors, implying a predominant role for cytokines in the pathophysiology of Hodgkin's disease as a tumor of cytokine-producing cells. PMID- 8519810 TI - Hormone resistance in cancer: the role of abnormal steroid receptors. AB - Breast tumors that have become resistant to endocrine therapy have been found to contain estrogen receptor (ER) variants due to aberrant splicing mechanisms of the ER gene. Exon skipping can give rise to dominant-positive receptors that are transcriptionally active in the absence of estrogen, or dominant-negative receptors that are themselves transcriptionally inactive but prevent the action of the normal receptor. ER splice variants similar to those in breast cancer have also been reported in human meningiomas. Androgen receptor (AR) variants have been detected in some prostate cancers that exhibit resistance to androgen therapy. In leukemia and lymphoma, mutations in the glucocorticoid receptor (GR) cause resistance to cell lysis by dexamethasone. Thus, there is increasing evidence that mutations in the genes of steroid receptors can cause loss of hormone dependency in different cancer types. PMID- 8519811 TI - Vaccination for treatment of tumors: a critical comment. AB - Tumors are resistant to the immune response as evidenced by both their progressive growth in patients despite specific humoral and cellular immune responses to tumor antigens and by the moderate clinical effect of active specific immunotherapy with tumor vaccines tested to date. This "immune resistance" may be due to various reasons, among which the most important ones are: (1) in the afferent pathway of the immune response, (a) expression of major histocompatibility complex (MHC)-class II molecules without coexpression of costimulatory B7 molecules on tumor cells, which impairs activation of T- and B cells and, (b) release of prostaglandins and other factors from tumor cells, that may inhibit proliferation and function of helper T-cells; and (2) in the efferent pathway; (c) release of tumor antigens, which blocks cytotoxic cells and antibodies and release of proteolytic enzymes, which degrades specific antibodies; (d) reduced expression of MHC-class I molecules by tumor cells, which inhibits their recognition by cytotoxic T-lymphocytes (CTL); and (e) cell membrane-associated inhibitors of complement factors that block complement mediated lysis. Altogether, the chance for a successful tumor therapy by tumor vaccines has to be estimated to be low. Alternatives would be to use tumor antigens as tumor cell targets for cytotoxic compounds with differing action from the cytotoxic mechanisms used by the immune system. The problems of low tumor localization rates of tumor-specific monoclonal antibodies, immune resistance of the tumor cells, and general toxicity of cytotoxic drugs may be solved by a biphasic therapeutic approach called immune specific enzyme-mediated chemotherapy. It uses, in a first phase, an appropriate antibody-enzyme fusion protein and, in the second phase, a nontoxic prodrug that is cleaved at the tumor site by the enzyme of the fusion protein into the cytotoxic drug. PMID- 8519812 TI - Contribution of MAV-1-induced nephroblastoma to the study of genes involved in human Wilms' tumor development. AB - The avian nephroblastoma induced by myeloblastosis-associated virus constitutes a unique animal model in which to study genes involved in the initiation and progression of the human Wilms' tumor. Along this line, we have identified a new cellular gene (nov, for nephroblastoma overexpressed) whose expression is regulated in vitro by the WT1 proteins and is stimulated in all avian nephroblastomas. The nov gene is also conserved in human and its expression is altered in Wilms' tumors. In both species, the nov gene encodes a potential insulin growth factor (IGF)-binding protein associated tot he extracellular matrix and likely to be involved in cell growth regulation. The recent data that are discussed in this review strongly suggest that the nov protein might play a critical role in normal and pathological nephrogenesis. PMID- 8519813 TI - The Ets family of proteins: weak modulators of gene expression in quest for transcriptional partners. AB - Members of the Ets family of transcriptional regulators play pivotal roles in physiological processes, such as embryonic development or immune response. The Ets family proteins possess unique regulatory features because they bind DNA as monomers and their respective activities rely more on their ability to interact with other transcription factors than on their specific binding to a cognate DNA sequence. This review focuses on such interactions and also explores dysregulated expression of the Ets proteins in human cancers. PMID- 8519814 TI - [Current aspects of hepatitis C diagnosis]. PMID- 8519815 TI - [IS6110 for typing strains of Mycobacterium tuberculosis: application of a standardized protocol with computerized image analysis]. AB - BACKGROUND: For the epidemiological control of tuberculosis it is necessary to use specific markers for strain differentiation. The analysis of the restriction fragment length polymorphism (RFLP) by using the insertion sequence IS6110 as a probe, allows us to establish accurately the strains which are around in a population. Our study evaluates the efficiency of this marker in 136 strains of Mycobacterium tuberculosis isolated from our surroundings. A standardized protocol is used, and a computerized system to analyze the images is described. METHODS: DNA restriction was done with PvuII. The filters were revealed by following a chemiluminescence method using a 867 bp probe, which is located to the right of the PvuII site IS6110. The comparison of the patterns obtained was done in a computer. The coefficient of Dice was calculated to express the similarity of the profiles given by two strains. The strains were clustered by the UPGMA method. The graphic representation of the clusters was done by means of homology dendrograms. RESULTS: 124 different patterns were obtained from which 118 strains had a unique pattern while 18 shared it. The index of discrimination was 0.996. Ninety two percent of the strains had more than 6 bands and none had no IS6110. The median of homology was 27% in 8 of the patients, 2 consecutive isolates were studied with the result of no variation seen on the patterns. CONCLUSION: IS6110 has shown very effective because of its stability and high discriminative power. The standardized protocol together with a computerized analysis of the images obtained allows comparison of results, furthermore, to establish centralized data base. This would be very useful for epidemiological studies of tuberculosis and the chase of strains with special characteristics. PMID- 8519816 TI - [Prevalence of Neisseria meningitidis carriers among the population of Cerdanyola (Barcelona)]. AB - OBJECTIVE: To determine the prevalence of Neisseria meningitidis (N. meningitidis) from healthy carriers and its resistance to penicillin in Cerdanyola population. To asses which risk factors were associated with healthy carriers and compare some epidemiologic characteristics between people with penicillin sensitive and penicillin resistant strains. METHODS: Cross-sectional seasonal study of 1500 individuals selected from day care centers, schools, colleges, cultural and working centers, located in different areas of Cerdanyola. We performed throat smears and immediate culture onto selective media for isolation of N. meningitidis. Data were evaluated by univariate and multivariate statistical analysis using the SPSS statistical package. RESULTS: One hundred and ninety-one (12.7%) individuals harbored N. meningitidis strains. In logistic regression multivariate analysis, meningococcal carriage significantly increased for the age group 14-18 years (OR = 4.55 with respect to the reference group, 0-3 years), in the spring (OR = 2.29), male sex (OR = 1.67), and active smoking (OR = 1.45, intervals of 10 cigarettes/day), while meningococcal carriage significantly decreased in the group under 4 years at age (OR = 0.55), with prior use of antibiotics (OR = 0.58) and with bigger housing space (OR = 0.84 for 10 m2/person). A 42% of N. meningitidis strains in carriers from this population showed decreased sensitivity to penicillin (MIC > 0.1 microgram/ml). We have not found significantly association between the variables studied and penicillin resistance among carriers of N. meningitidis. CONCLUSIONS: Age, spring season, sex, active smoking and overcrowded housing are significantly associated to carrier state. Prior use of antibiotics decreased to carrier state. According to our findings, reducing smoking habits and improving housing conditions may be useful measures to reduce the prevalence of carriers. PMID- 8519817 TI - [Osteoarticular infections by Salmonella non-typhi]. AB - BACKGROUND: The aim of this study was to know the clinical characteristics of osteoarticular infection by Salmonella non typhi (SNT) in Spain. PATIENTS AND METHODS: The medical records of 14 patients with osteoarticular infection by SNT from January 1970 to December 1992 were reviewed. RESULTS: Over the above mentioned 23 years, 1334 patients had been diagnosed with one or more SNT isolations, with 14 (1%) having osteoarticular infection. Seven patients had septic arthritis, 3 osteomyelitis and 4 mixed infection (arthritis and osteomyelitis). Thirteen patients (93%) presented with underlying systemic disease (immunosuppression 12 cases [86%] and hemoglobinopathy 1 case [7%]) and 5 (36%) had predisposing osteoarticular disease. The most commonly affected joint was the knee (9.58%). Involvement was monoarticular in 8 episodes (73%). Out of the 7 cases with osteomyelitis, 4 (57%) were secondary to an articular foci and 3 (43%) were of hematogenic origin. The femur (4 cases, 44%) and the tibia (4 cases, 44%) were the most frequent localizations. On nine occasions (64%) the cultures remained positive 7 days after initiation of antibiotic treatment. Only one patient died as a consequence of the articular infection. CONCLUSIONS: Osteoarticular infection by Salmonella non typhi should take the existence of immune disorders into account. PMID- 8519818 TI - [Treatment of acute bacterial meningitis: present and future]. PMID- 8519819 TI - [Microsporidia: an animal parasite of growing interest in human pathology]. PMID- 8519820 TI - [Treatment of peptic ulcer and gastritis associated with Helicobacter pylori]. PMID- 8519821 TI - [Nosocomial infections caused by anaerobes]. PMID- 8519822 TI - [Necrotic surgical wound]. PMID- 8519823 TI - [Cefpodoxime]. PMID- 8519824 TI - [Chronic meningococcemia caused by Neisseria meningitidis of serogroup C]. PMID- 8519825 TI - [Spontaneous splenic rupture during infectious mononucleosis. Resolution with conservative treatment]. PMID- 8519826 TI - [Hemophagocytosis syndrome associated with acute HIV infection]. PMID- 8519827 TI - [Transitory monoclonal gammopathy and acute Q fever]. PMID- 8519828 TI - [2 cases of ocular infestation by Oestrus ovis]. PMID- 8519829 TI - [Cauda equina syndrome with elevated adenosine deaminase in a patient with HIV infection]. PMID- 8519830 TI - [Macrolides and Helicobacter pylori]. PMID- 8519831 TI - [Comparative study of 2 culture methods by seeding, in hemoculture bottles, the dialysis fluid from patients in continuous ambulatory peritoneal dialysis]. AB - BACKGROUND: Peritonitis remains a major complication of continuous ambulatory peritoneal dialysis (CAPD). The accurate diagnosis of peritonitis is a requirement for a successful CAPD program. A prospective study was performed to evaluate two culture methods. METHODS: 1. Culture of 10 ml of uncentrifuged peritoneal fluid and 2. Culture of the sediment of 50 ml centrifuged and resuspended in 20 ml of distilled water, into aerobe/anaerobe hemoculture bottles (Hemoline, BioMerieux). We processed 162 PF from 138 CAPD peritonitis episodes, 33 of whom were in antimicrobial drug therapy. RESULTS: The sensibility/specificity of both methods (87.0/70.8 method 1 and 81.9/79.2) were similar. Both methods were more sensitive (p = 0.001) when the patient was no in antimicrobial drug therapy (60.6/88.6 method 1 and 69.7/92.4 method 2). We isolated 132 microorganisms, 64.4% Gram positive, 25.0% Gram negative, 4.6% anaerobes and 6.1% levures. CONCLUSION: Both methods were similar and the more important factor to increase the yield of culture is to remove the antibiotic presents in centrifuged fluid. PMID- 8519832 TI - [Presence of virulence factors and pathovars in strains of Campylobacter jejuni isolated from patients with diarrhea and healthy children]. AB - BACKGROUND: To study the prevalence of virulence factors (adhesion, invasion, cytotoxicity and hemolytic activity) and to establish the presence of pathovars (virulence phenotype) in C. jejuni strains isolated in pediatric patients with inflammatory and secretory diarrhea and asymptomatic carriers. METHODS: We analyzed 95 strains of 48 patients with inflammatory diarrhea (blood and mucus in feces), 30 patients with secretory diarrhea (watery) and 17 strains isolated in asymptomatic children (control group). The study of adherence capacity, invasion and cytotoxicity was made in the Hep-2 cell line, and the analysis of hemolytic activity in blood agar plates with a 5% sheep's blood. The pathovars were defined by the cellular adhesion (phenotypes A and a) and the cytotoxicity (phenotypes E and e). RESULTS: 29.1% of inflammatory strains presented adherence capacity, 66.6% were invasive, 64.5% cytotoxic and 52.1% hemolytic. In the secretory strains the values were 70, 20, 10 and 6.6% respectively; in the control group the 11.7% presented adherence capacity and 5.8% were invasive. We obtained difference statistically significative for the secretory strains in the adherence capacity, and in inflammatory strains in the adherence capacity, cytotoxicity and hemolysis. The phenotype Ae predominate in the secretory strains, and the phenotype ae in the strains belonging to the control group. No pathovar predominates in the inflammatory strains. CONCLUSIONS: The analysis of virulence markers permit us to establish the pathogenic behaviour of the C. jejuni strains isolated in patients with diarrhea. The study of the adherence capacity and cytotoxicity (pathovars) would be used as a virulence markers and to predict the inflammatory or secretory nature of the diarrhea caused by C. jejuni strains. PMID- 8519833 TI - [Detection of antibiotic resistance in Enterococcus sp. Comparison of GPS-TA (BioMerieux-Vitek), Uniscept MIC-3 (bioMerieux-Vitek) and conventional methods]. AB - BACKGROUND: The treatment of severe enterococcus infections requires synergism of a beta-lactamic or glycopeptide and a aminoglycoside, but when resistance to first one or high-level resistance to aminoglycosides are present, synergism would be lost. We compared the adequacy of two commercially available systems to detect antibiotic resistance. METHODS: We studied 158 isolates of Enterococcus sp., with high-level resistance to gentamicin (40 isolates) and streptomycin (89 isolates), resistance to ciprofloxacin (34 isolates), resistance to ampicillin (7 isolates) and with intermediate susceptibility to vancomycin (3 isolates). No one was beta-lactamase producer by Cefinase disk method. We use disk diffusion as reference technique to detect high-level streptomycin resistance. The susceptibility to the remainder antibiotics was studied by agar dilution method, according to NCCLS. We studied the accuracy of GPS-TA cards and Uniscept MIC-3 in relation to the degree of agreement with conventional means, following FDA criteria. RESULTS: Essential agreement for MIC was less than 90 with MIC-3 for ampicillin (81.5%) and ciprofloxacin (71.3%). Categorical agreement rate was less than 90% (76.4%) and major error rate was higher than 3% (10.9%) with the use of MIC-3 for ciprofloxacin. Very major errors for ampicillin, vancomycin and ciprofloxacin were not produced by any system. The very major error rates for high level resistance to gentamicin and streptomycin with GPS-TA card were 5 and 15.7%, respectively. CONCLUSIONS: We do not recommend the use of the Uniscept MIC 3 panel with visual reading to detect susceptibility to ciprofloxacin. Detection of high levels of aminoglucoside resistance by GPS-TA card should be supplemented with conventional techniques because of the high rate of major error. Due to the low number of strains that have been studied, we can not assure the suitability of these systems to detect ampicillin or vancomycin resistance. PMID- 8519834 TI - [Activation of cell death in lymphocytes from individuals infected with HIV]. AB - BACKGROUND: In HIV infection, T cells depletion cannot only be explained by direct viral infection. Programmed cell death (PCD), also know as apoptosis or activation-induced cell death, may be responsible for the deletion of reactive T cells that contributes to HIV induced immunodeficiency. We studied the response of lymphocytes in vitro to different polyclonal and oligoclonal (superantigen) activators, and tested whether the stimulation of T cells from individual with HIV infection lead to cell death. MATERIAL AND METHODS: Peripheral blood mononuclear cells, total T lymphocytes, TCD4+ and TCD8+ cells from 10 positive patients, 2 patients with AIDS and 10 negative individual for the virus were cultured in RPMI medium and subjected to stimulation with PHA, PWM and SEB (staphylococcus B enterotoxin). Trypan blue was used to distinguish viable from dead cells. RESULTS: TCD4+ cells from HIV-infected patients die after SEB or PWM activation (almost 40% from asymptomatic and 80% from AIDS), and do not die TCD8+ from the same individuals (around 10-15%), or T cells from seronegative controls. CONCLUSIONS: Lymphocytes from patients with HIV-infection showed as abnormal proliferative response to self-MHC class II restricted recall antigens and PWM whereas the response to PHA was conserved. Probably, apoptosis is triggered by an aberrant form of T cell activation in the mature TCD4+ cell population in HIV infected individuals. PMID- 8519835 TI - [Urinary infections: specific aspects]. PMID- 8519836 TI - [Multicenter study of infectious complications in parenteral drug addicts in Spain: final analysis of 17,592 cases (1977-1991). Working Group for the Study of Infections in Drug Addicts]. PMID- 8519837 TI - [The AIDS virus: strategies for attacking it]. PMID- 8519838 TI - [Lyme borreliosis: epidemiologic and etiopathogenic aspects]. PMID- 8519839 TI - [Palmoplantar exanthema in a drug abuser]. PMID- 8519840 TI - [Sensitivity tests to antifungal agents for yeasts based on the standards proposed by the NCCLS in 1992]. PMID- 8519841 TI - [Actinobacillus ureae isolated from a patient with chronic bronchitis]. PMID- 8519842 TI - [Colonization of a parenteral nutrition catheter by Malassezia furfur in an adult]. PMID- 8519843 TI - [Convulsions induced by imipenem in an HIV-positive patient]. PMID- 8519844 TI - [Infection by Malassezia furfur associated with a catheter in a premature child]. PMID- 8519845 TI - [Usefulness of the Granada culture media in the detection of pregnant women carrying Streptococcus agalactiae]. PMID- 8519846 TI - [Endocarditis caused by Streptococcus pneumoniae. Report of 3 new cases]. PMID- 8519847 TI - ["Nutricion Hospitalaria", scientific vehicle for all]. PMID- 8519848 TI - [Home and ambulatory artificial nutrition. Enteral nutrition. The NADYA Group]. AB - Home enteral nutrition is, at present, a therapeutic alternative which can be applied to a great number of patients who only require hospitalization for the nutritional treatment, thus improving their quality of life and reducing costs. The experience in this field is great in other countries, and we believe its use is growing in Spain. To better understand this situation, the data of 589 patients from 25 hospitals of the entire national territory, have been evaluated. When analyzing the diseases which led to the instigation of enteral nutrition, the most frequent causes were found to be neurological afflictions and tumoral processes. At the time of establishing the indication, only 50% of the patients were undergoing curative therapy. The nasogastric tube was used in the majority of cases (69%), even during prolonged periods of time. The formula of enteral nutrition which was most used was the standard, possibly due to the difficulty of acquiring other types of formulas when this is not specifically indicated. The formula is frequently administered by syringe (44%) and by bolus (41%). The cost of the formula and the necessary infusion material, was mainly carried by the referring hospital. The complications registered were rare (0.18 episodes/patient) and of a slight character, of gastrointestinal of mechanical origin, which could be resolved in the home. The follow up of the patient was done in similar percentages by the Departments of Nutrition, by the at home hospitalization teams, and, in a coordinated way, between Nutrition and Primary Attention. 23 % of the patients finished the treatment due to improvement, 20 % died, and 15 % continued treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519849 TI - [Home and ambulatory artificial nutrition. Parenteral nutrition. The NADYA Group]. AB - In recent years and increase in the use of parenteral nutrition in the home, as an alternative to covering the nutritional needs of patients incapable of covering them orally or enterally and who do not require hospitalization, is being seen. The number of patients undergoing treatment with, or as candidates for, this specialized nutritional support in Spain, is unknown. The data of 39 patients from 10 therapeutic teams at the national level, have been collected and evaluated. With an average age of 42 years, 54% were male. The pathology which most frequently indicated a need for at home parenteral nutrition was mesenteric thrombosis, followed by intestinal inflammatory disease (24 and 18%). The indication was definite in 54% of the cases. The blood vessel most frequently accessed was the subclavian (73%), preferently using tunneled catheters of the Hickman type (53%), and scarcely using the implanted type (6%). Practically all patients receive individualized formulas, adapted to their nutritional needs. The infusion is nocturnal in 65% of the cases, and only 58% of the cases use an infusion pump. IN the majority of cases, the supply of the formulas as well as the infusion material, is taken on entirely by the reference hospital which also takes care of the follow up of the patient. An adequate network of distribution which enables the patient to access this material in his usual environment, is not available. An improvement in quality of life and nutritional state is seen in the evaluated patients, of which 41% finished treatment (transitory indications), 23% had died, and the rest continued treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519850 TI - [National Task Force on Home and Ambulatory Artificial Nutrition. NADYA. The NADYA Group]. AB - When a patient needs parenteral or enteral nutrition, be it in a transitory way or as a permanent form, and hospitalization is not strictly required, this treatment should take place in the home of the patient whenever possible. The support with artificial nutrition can be equally efficient, improving the life expectancy ad the quality of life of patients who would otherwise be faced with a much prolonged hospital stay. The Ambulatory and Home Artificial Nutrition group (NADYA) is a multidisciplinary team of health care professionals, from different areas of the national territory, who are dedicated to Clinical Nutrition. With the objective of promoting health and well-being of patients undergoing treatment, and to ease the therapeutic activity of the implicated professionals, this group has developed a series of suggestions for the practice of enteral or parenteral nutrition in the home of the patient. These suggestions include specifications about the technical team, criteria for selection and training of the patients, routes of access, formulas and material needed, follow up characteristics, and associated complications, and the represent a consensus of the regulations necessary for the guarantee of an adequate level of security and efficiency of the at home care of patients who require artificial nutrition support. PMID- 8519851 TI - [Home parenteral nutrition in the management of patients with chronic idiopathic intestinal pseudo-obstruction]. AB - Home parenteral nutrition is indicated in all those patients who are unable to cover all their needs orally or enterally during prolonged periods of time, and who do not require any other general care other than the parenteral nutrition. Our objective is to prove the use of home parenteral nutrition as a nutritional support in patients with severe forms of chronic idiopathic intestinal pseudo obstruction. In our unit, three patients with this disease, have received home parenteral nutrition between 1993 and the present date. One patient received it during four months, with the catheter being removed due to a fungemia. At present she is being maintained with oral and enteral nutrition. The other two patients continue in the program: one since October 93 and the other since July 94. The hydroelectric alterations caused during the episodes of sub-occlusion make more frequent changes in the composition of the parenteral nutrition necessary, compared to other types of patients. The low incidence of complications and the degree of acceptance by the patient makes this technique an ideal method for the long term nutritional support. PMID- 8519852 TI - [Our experience with ambulatory enteral nutrition]. AB - Enteral nutrition in the home of the patient, has gained interest in recent years. In our health care area, we do not have a Unit of at Home Hospitalization, which has not prevented the implementation of this therapeutic modality in certain types of patients. 89 cases who have undergone enteral Nutrition in their home after the last hospital admission, were reviewed. According to the basic pathology, 41.6% (37 patients) correspond to neurological patients; 51.7% correspond to neoplasmic patients, and 6.7% are classified as miscellaneous. The average age is 64 years (18 months-92 years); the mean caloric ingestion is 1,520 Kcal/day (500-2,500), and the duration is a mean of 315 days (7-1,560). The complications observed through ambulatory visits of the patient and/or the family, accounted for a total of 36, of which 30 (83%) were digestive, and were corrected with the usual methods. In 8 cases (22%), it involved mechanical complications, and only 2 cases involved metabolic complications. Only 1 serious complication (massive bronchoaspiration) could have been avoided. The results indicate a good degree of acceptance, with similar results to those described by other authors, and with a low incidence of severe complications. PMID- 8519853 TI - [Nutrition and bacterial translocation]. AB - The present work is part of a presentation given at the Scientific Meeting of the Association for Surgical Nutrition and Metabolism, during the XX National Congress for Surgery (Madrid, November 1994). The authors, prior to presenting their experiences, define and high light the importance of the phenomenon of "Bacterial Translocation" (BT). Afterwards, and based on several experimental studies performed by them, they attempt to answer two questions: 1) Is the term BT correct? 2) Is BT a physiological or a pathological state? Finally they review the relationship which exists between bacterial translocation and nutrition, both from a causative point of view as from the prevention and therapy of the same. PMID- 8519854 TI - [Cytometric study of colonic tumors in a model of experimental colonic cancer. Impact of the diet]. AB - Butyrate is a short chain fatty acid, made up of four carbon atoms. Along with acetate and propionate, they are the main volatile fatty acids formed by the microbial fermentation of the carbohydrates of dietary fibre in the colon, mainly in the caecum. Additionally, they acidify the intracolonic pH, and they play an important role in the regulation of the absorption of water and sodium. On the other hand, they are, especially butyrate, preferred by the colon cell, as sources of energy alternative to glucose. Besides this, butyrate, in cellular cultures, is a known antineoplasic agent which is characterized by doubling the cellular duplication time for cells in the G1 phase, it increases the activity of certain enzymes, it stimulates the effects of interferon, it modifies the morphology of the cells, which in some cases leads to the reversion of the characteristic transformations of the cancerous cells, and it produces alterations in the chromatin, the nucleoli, elements of the cytoskeleton and the Golgi apparatus. Even though it is not known how it causes these actions, it is thought that the acetylization of histones which it produces, may be an important mechanism. We analyzed the effect of this substance in a colonic carcinogenesis model in Sprague-Dawley rats, in which the tumors were induced with the alkylating agent 1,2-dimethylhydrazide, observing the cytometric pattern of the tumors, and the possible differences between both groups. In one of them, sodium butyrate was continuously infused by means of a intrathecal catheter at a rhythm of 1.5 ml/hour during the tumoral induction which lasted four weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519855 TI - [Physiology and physiopathology of postoperative disease. Therapeutic implications]. AB - The organism responds to each and every aggression by means of a neuro-endocrine activation, which is translated into a metabolic change. The action of the surgeon should not be any other than to improve the neuro-endocrine-metabolic response. This review describes the physiological and physiopathological occurrences which develop in every traumatized patient. PMID- 8519856 TI - [Hormones, growth factors, and drugs in metabolism and nutrition]. AB - The manipulation of the inflammatory and hormonal responses may produce, on one hand, positive effects, and, on the other hand, potentially negative effects. The modification of the neuro-endocrine-humoral pattern may become more important and effective than the supply of nutrients. In this article we bring an up date of the role of insulin, anabolic steroids, blocking the catabolic hormones, phenobarbital, somatostatin, clenbuterol and metaprorenol, growth factors: GH and IGF-1, cytokines, and anti-cytokines sera. The use of GH, IGF-1, and of the epidermal and or colonic growth factors, along with a blocking of the cytokines, the manipulation of the lipidic mediators, and the supply of classical nutrients, specific to the aggression situation, may improve the protein synthesis and tissue repair. It may at the same time both decrease the loss of body proteins as well as promoting and acceleration of the recovery, shortening the hospital stay and reducing the convalescence time. The future seems to point towards molecular and cellular biotechnology and towards "nutritional" pharmacology, which contemplates the effects of growth factors, the recent advances in the field of cytokine modulation, and the manipulation of the binomer nutrient-medication. PMID- 8519857 TI - [Total peptic activity in gastric juice and peptic cell mass (chief fundic cells and mucopeptic fundic-antral cells): cellular-secretory correlations in normal subjects]. AB - The aim of this experience has been to evaluate cytosecretory correlations between total peptic activity in gastric juice and gastric peptic cell mass (chief cells and fundic-antral mucopeptic cells) in normal subjects. Gastric peptic cell mass and total peptic activity do not change depending on sex. Concerning age, in spite of a significant decrease of gastric peptic cell mass, peptic activity does not significantly decrease. This apparent disagreement between decreasing anatomic data and functional data, remaining unchanged, may be explained by analyzing the behaviour of fundic and antral peptic cell masses in detail. A difference emerges in the behaviour of chief and mucopeptic cells. The first decrease significantly after 50 years, while the second ones do not show variations, regardless of their fundic and antral location. In particular, fundic mucopeptic cell component increase, but not significantly. The lack of variation in peptic activity in gastric juice after 50 years may be assumed to be connected with the unchanged integrity of mucopeptic cells. PMID- 8519859 TI - [Acute pancreatitis: clinical-tomographic correlations]. AB - The authors are interested in verifying the correlation between clinical findings and CT scan imaging in acute pancreatitis. Forty-one patients with acute episodes of pancreatitis are studied according to classic clinical Ranson prognostic factors and radiological Hill classification. All patients are investigated with G.E. 9800 Quick TC scanner. Our data show a significant correlation especially for patients of extreme classes: 78.3% of patients in first Ranson class are included in 0-I-II Hill grades, 74% of the patients in the cumulative third and fourth Ranson classes are correlated with IV and V Hill grades. Finally the authors underline the usefulness of clinical and tomographic evaluation for prognostic and therapeutical trends in patients with acute pancreatitis. PMID- 8519858 TI - Early prediction of aetiology and severity of acute pancreatitis by serum amylase and lipase assays. AB - OBJECTIVE: To evaluate whether simple pancreatic enzyme assays are useful in the early assessment of aetiology and prognosis of acute pancreatitis. DESIGN: A retrospective clinical study. SETTING: Department of Internal Medicine with a Pancreatic Disease Centre. PATIENTS: The study included 246 patients with acute pancreatitis admitted to our Unit within the first 24 hours from the onset of disease. Amylase and lipase serum levels and lipase/amylase ratio were evaluated. RESULTS: Serum amylase was higher in patients with necrotizing pancreatitis than oedematous and biliary pancreatitis than alcoholic (p < 0.009 and p < 0.05 respectively), but a high degree of overlap between values was found. No differences were noted in lipase serum levels. Lipase/amylase ratio was not different between patients with alcoholic and nonalcoholic pancreatitis. CONCLUSIONS: Evaluation of serum amylase and lipase is not useful for assessing aetiology and severity of acute pancreatitis, although amylase may be higher in severe and biliary forms. PMID- 8519860 TI - [Selective use of intra-operative cholangiography in gallstone surgery]. AB - The authors report their experience of the use of intraoperative cholangiography in 350 operations for biliary stones. The cholangiography was performed on all 52 patients with preoperative diagnosis of stones in CBD. In the 298 patients with gallbladder stones intraoperative colangiography was performed in 32 times, on the basis of previous jaundice, pancreatitis, microlithiasis, enlarged cystic duct or choledochus, and suspected palpatory reports of hepatic duodenal ligament. Intraoperative colangiography showed stones in all the patients of the first group and in 8 (25%) of the second. No patients reported disturbances attributable to residual stone with an average follow-up of 6 months. PMID- 8519861 TI - [Diagnostic aspects of spontaneous bacterial peritonitis in hepatic cirrhosis with ascites]. AB - Spontaneous bacterial peritonitis (SBP) is a severe complication appearing in 8 22% of hepatic cirrhosis with ascitic decompensation. The authors describe 6 cases of SBP in hepatic cirrhosis. SBP diagnosis has been confirmed by isolation of the aetiological agents in the ascitic fluid, and PMN count above 250/ml in 12% of the studies cases. SBP diffusion and the high mortality risk justify the examine of the ascitic fluid also in asymptomatic patients. PMID- 8519862 TI - [Measurement of anti-HCV IgM antibodies with an experimental kit]. AB - The aim of this study was to search for specific anti-HCV IgM antibodies. The author proposes an immunoenzymatic method used to assay IgM specific antibody utilising routinely available techniques. The study was performed over a two month period in out-patients referred by general practitioners for anti-UCV antibody assay to the Immunohematology and blood transfusion Service in Foggia. A total of 206 subjects were examined. Anti-HCV IgM antibody assay is made possible by a two-step procedure: the absorption of IgM-type rheumatoid factor and the use of anti-IgM antibodies conjugated with alkaline phosphatase. After preincubation of the serum diluted in absorption medium, the sample is set on a sensitised plate and incubated overnight. After washing and the addition of anti-HCV IgM antibodies conjugates to alkaline phosphatase, the plate is again incubated for 90 min at 37 degrees C. This is followed by washing and the deposition of the substrate, before a further 30-min incubation at 37 degrees C. A blocking solution (NaOH) is then added and the plate is read at 405 nm. Data obtained only indicated the positivity or negativity to the routine test or to the experimental test: for organisational reasons it was not possible to perform a follow-up of positive subjects or observe the correlation with other disease markers. Out of a total of 209 subjects examined, 8 (3.8835%) were positive to both IgG anti-HCV IgM, whereas 10 (4.8544%) were positive to anti-HCV IgM alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519863 TI - [Breakfast habits in moderately obese adults and its effect on daily energy and nutrient intake, on alcohol consumption and on various clinical and anthropometric parameters]. AB - It is widely held that obesity may be due to alterations in the total caloric intake, the distribution of nutrient intake and the number of meals; widely spaced out meals of large proportions may be associated with metabolic dysfunctions. An observational study was performed in a random sample (80 males and 183 females) of moderately obese adults (IMC > 30 and < 40) attending the dietary unit of our hospital to evaluate spontaneous breakfast eating habits (understood as caloric contribution > 10% of daily caloric intake) in relation to: working activity, region of origin, possible influence on daily intake of energy and nutrients and on common clinical and anthropometric variables (arterial pressure, glycemia, cholesterolemia, triglyceridemia, IMC, WHR). Following the subdivision of patients into breakfast eaters (SC = 26 males, 52 females) and non-breakfast eaters (NC = 54 males and 131 females), no significant differences emerged between sexes with regard to region of origin, working activity, IMC, WHR, total kcal, distribution of nutrients, glycemia, cholesterolemia, triglyceridemia, arterial pressure. The only significant difference between SC and NC concerns alcohol consumption which was inversely correlated to breakfast eating in both males and females (males: r = -0.225, p < 0.05; females: r = -0.157, p < 0.05). No significant differences appear between wine consumers (SE = 29) and abstemious males (NE = 51), except for daily caloric consumption (kcal/die), triglycerides and arterial pressure, which were higher in SE (p < 0.05, p < 0.01, p < 0.05 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519864 TI - [Unusual presentation of celiac disease in adult age]. AB - The author report the case of a 23 year old female, where a severe iron deficiency anemia was the only clinical expression of coeliac disease. This nonspecific appearance and similar reported observations with selected intestinal malabsorption emphasize the risk of diagnostic misleading in the prospective of atypical symptoms. The subsequent result is no glutin free diet style, with its protective role against malignancy. The non invasive screening method with related antibodies determinations is stressed important diagnostic tool. PMID- 8519865 TI - [Aneurysm of the hepatic artery. A case report]. AB - The authors describe the case of the sixty-one-year-old man admitted to hospital because of a growing jaundice that after the surgical operation proved to be caused by a compression of the PBV determined by a voluminous aneurysm of the hepatic artery. The integrity of the gastroduodenal artery made it possible to make a simple aneurysmectomy with clinic. The patient was discharged from hospital after fifteen days from the surgical operation; he was surgically healed and with normal enzymatic values. The follow-up two years after discharge confirmed a hematochemical state within normal limits. PMID- 8519866 TI - [Merkel cell tumor. A clinical case]. AB - Merkel's tumor cells represent a rare neuroendocrine neoplasia type which belong to an apudomi group but it's different due to the absence of the biogen amine and hormone polypeptide production. The authors report a rare case of Merkel's tumor cells clinically evident with a great neoformation under the left axilla but already represents at the moment of discovery a notable diffusion with repetition as in hepatic and suprarenal gland. Pointing out not only clinic case having arrived at their observance but also it's important to take note of this particular neoplasia and to suspect it in case of doubt interpretation of clinical tumor. PMID- 8519867 TI - The European Journal of Surgery--present situation and future strategy. PMID- 8519868 TI - Beyond the scalpel--concepts, methods, and structures for reporting surgical results. PMID- 8519869 TI - The importance of socioeconomic issues in surgical outcomes: what is a relevant end point? PMID- 8519870 TI - Measurement of disability after multiple injuries: the functional independence measure. Clinical review. AB - Collection of data about injured patients must include a description of the injuries using the International Classification of Disease (ICD9) and their severity using the Anatomical Injury Scale (AIS) from which the Injury Severity Score (ISS) is calculated. This method was developed for assessing the risk of mortality and is a good way of defining the extent of injury or impairment. Morbidity after injury is equally important. The terms "disability", (relating to the individual person's behaviour and performance of activities) and "handicap" (relating more to the disadvantage for a given patient in society) are accepted as the two main sub headings of long term morbidity. There are limitations to total overall health measurements and a functional disability approach is necessary for patients with multiple injuries. Of the different assessment tools the Functional Independence Measure, originally developed in Buffalo, USA, has been chosen as the most reliable and valid as it has the additional advantage of a large database containing the records of 200,000 patients throughout the world. This has been introduced at the Royal London Hospital to measure the disability outcome of patients brought there by the Helicopter Emergency Medical Service. PMID- 8519871 TI - Transhiatal oesophagectomy compared with transthoracic resection and systematic lymphadenectomy for the treatment of oesophageal cancer. AB - OBJECTIVE: To compare the results of transhiatal oesophagectomy with those of transthoracic resection with systematic two field en bloc lymphadenectomy in the treatment of carcinoma of the oesophagus. DESIGN: Prospective open (non-random) study. SETTING: University hospital, Germany. SUBJECTS: 87 patients with carcinoma of the oesophagus of whom 46 underwent transhiatal, and 41 transthoracic resection. MAIN OUTCOME MEASURES: Morbidity and short and long term mortality. RESULTS: The type of operation was chosen on clinical grounds, and the groups were comparable except for site and type of tumour, and nodal stage. The hospital mortality was 7/46 (15%) in the transhiatal group and 4/41 (10%) in the transthoracic group. The most common complication was anastomotic leak (23/46, 50%, compared with 10/41, 24%, p = 0.014), followed by major pulmonary complications (16/46, 35%, compared with 12/41, 29%), and cardiac complications (12/46, 26% compared with 11/41, 27%). Median survival was 350 days in the transhiatal group and 378 days in the transthoracic group. The percentage survival after one, two, and three years in the two groups was 48 and 55, 26 and 18, and 21 and 17, respectively. There were no significant differences in short or long term mortality. CONCLUSION: We have been unable to show that the oncologically more radical procedure (transthoracic resection with systematic two field en bloc lymphadenectomy) results in longer survival, but we have shown that it can be done with similar morbidity and short term mortality. Because it is possible to stage the disease exactly with a transthoracic resection, and because published reports from other centres have hinted at improved prognosis after it, we shall continue to do the operation for suitable patients. PMID- 8519872 TI - Evaluation of residual vascularisation in oesophageal substitution gastroplasty by surface oximetry-capnography and photoplethysmography. An experimental study. AB - OBJECTIVE: To evaluate residual vascularisation in gastroplasty and its possible relation to the development of anastomotic fistulas or dehiscences after oesophageal resection. DESIGN: Experimental open study. MATERIAL: Eleven mongrel dogs. INTERVENTIONS: Gastric parietal blood flow was evaluated by photoplethysmography and measurement of surface oxygen and carbon dioxide tensions under basal conditions and after Akiyama's tubular gastroplasty. Temperature, heart rate, and electrocardiogram; arterial pressure, pulmonary arterial pressure, pulmonary capillary pressure, central venous pressure, cardiac output, venous oxygen saturation, and arterial blood gas tensions were monitored under stable haemodynamic conditions. RESULTS: After gastroplasty, the mean serosal oxygen tension (pO2) of 8.6 mmHg and carbon dioxide tension (pCO2) of 99.5 mmHg and residual photoplethysmographic wave amplitude (8%) indicated considerable severe ischaemia at the fundus. There was relative ischaemia of the mid-stomach with residual mean values of 52.7 mmHg, 77.8 mmHg, and 57% for pO2; pCO2 and PPG wave amplitude, respectively. CONCLUSIONS: Important devascularisation of the fundus, theoretically incompatible with healing, occurs after gastroplasty. Operative photoplethysmography and surface measurements of pO2 and pCO2 are good ways of evaluating the level and degree of ischaemia in gastric tubes for oesophageal replacement. PMID- 8519873 TI - Gastric cancer: prognosis and lymph node reactivity. AB - OBJECTIVE: To assess the prognostic value of various immunomorphological variables in the prognosis of gastric cancer after curative resection. DESIGN: Retrospective study. SETTING: University hospital, Italy. SUBJECTS: 180 Patients who underwent curative resection for carcinoma of the distal two thirds of stomach between January 1960 and December 1978. Curative was defined as no residual cancer at the resection margins and no distant metastases. INTERVENTIONS: All living patients were followed-up, and missing survival data were obtained from the Official Census Registry. MAIN OUTCOME MEASURES: Correlation between survival and nuclear grade, lymphocytic infiltration, and types of lymph node reaction such as sinus histiocytosis, paracortical lymphoid cellular hyperplasia, and follicular hyperplasia in the cortical area. RESULTS: Crude 5 year and 10 year survival rates were 46% and 36%, respectively. Sex, site, and histological type of the tumour did not correlate with survival. Multivariate analysis showed that only pTNM stage of disease and degree of sinus histiocytosis were significantly related to survival. CONCLUSION: There may be an argument for using the presence or absence of sinus histiocytosis to stratify patients in prospective studies of adjuvant treatment. PMID- 8519874 TI - Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. AB - OBJECTIVE: To evaluate the effects of continuous hyperthermic peritoneal perfusion (CHPP) together with standard chemotherapy on the prognosis of patients with gastric cancer invading the serosa. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 174 patients who had undergone curative resection for gastric cancer invading the serosa (T3) between 1980 and 1989, 78 of whom had been randomised to be treated with CHPP after operation and 96 who received standard chemotherapy. INTERVENTIONS: CHPP was done immediately after operation; 8-10 l fluid containing 80-100 mg/m2 mitomycin C was perfused at a rate of 100-200 ml/minute, and inflow and out flow temperatures were maintained at 44-45 degrees C and 40-42 degrees C, respectively. This was followed by a standard regimen of mitomycin C and 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil (1:4) (UFT). The control group received the standard regimen only. MAIN OUTCOME MEASURES: Five year survival and patterns of recurrence in three groups: no lymph node metastases, 1-9, and 10 or more. RESULTS: Only in the group with 1-9 lymph node metastases was there an appreciable but not significant difference in 5 year survival: 66% compared with 44% (p = 0.084). The mean disease free survival for patients with peritoneal metastases was 30 months in the CHPP group compared with 23 months among the controls. CONCLUSION: CHPP improved prognosis in patients with T3 gastric cancer who had only 1-9 metastatic lymph nodes. PMID- 8519875 TI - Management of cholestasis in patients with chronic pancreatitis: evaluation of a treatment protocol. AB - OBJECTIVE: Audit of the protocol that we have developed for treating patients with chronic pancreatitis and cholestasis. DESIGN: Prospective open study. SETTINGS: University hospital, Finland. PATIENTS: 77 Patients admitted to hospital between 1992-93 with chronic pancreatitis, 18 of whom also had cholestasis (23%). INTERVENTIONS: Eight patients were treated with observation only, one with percutaneous transhepatic biliary stenting, and nine patients were operated on. Hepaticojejunostomy was done in four patients, and pancreatic resection-either a pylorus-preserving Whipple operation or a duodenum-preserving Beger's operation-in five patients. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Seven of the eight patients treated conservatively recovered and their cholestasis had resolved within a month, but one died of acute fulminant cholangitis which was initially misdiagnosed as an acute exacerbation of chronic pancreatitis. The patient treated by percutaneous stenting died of secondary biliary cirrhosis and liver failure; she had been jaundiced for several months before referral to our department. Cholestasis resolved in all patients who were operated on. After hepaticojejunostomy one patient was reoperated on for bleeding and recovered. After pancreatic resection one patient developed a wound infection, central venous catheter infection, and pneumothorax, and recovered. CONCLUSION: Cholestasis associated with chronic pancreatitis may be treated by conservative monitoring, biliary stenting, biliary bypass, or pancreatic resection depending on the clinical, biochemical, and radiological stage of the disease. PMID- 8519876 TI - Elective abdominal operations alter the free amino acid content of the human intestinal mucosa. AB - OBJECTIVE: To assess the impact of a standard moderately severe surgical operation on the mucosal amino acid content of the duodenum and the colon. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Nine patients who were to undergo elective open cholecystectomy. INTERVENTIONS: Endoscopically obtained biopsy specimens from the intestinal mucosa. MAIN OUTCOME MEASURES: Changes in the content of free amino acids in the duodenum and colon at three days postoperatively. RESULTS: The concentration of glutamine in the duodenum increased by 27% and that of glutamic acid by 34% after operation, whereas their content in colon remained unaltered. The concentration of branched chain amino acids increased by 26% in the duodenal mucosa after operation and by 24% in the colonic mucosa. The total concentration of amino acids (excluding taurine) increased by 9% in the duodenum, but remained unaltered in the colon. CONCLUSION: This study shows characteristic and consistent alterations in the free amino acid content of the intestinal tract after a moderately severe operation. PMID- 8519877 TI - The pressure area: a variable for the assessment of anal sphincter function. AB - OBJECTIVE: To assess the contribution of the area under the resting and squeeze pressure curves, respectively, in the measurement of anal sphincter function. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: 106 Healthy volunteers (73 women and 33 men) with no signs or symptoms of anorectal disease. INTERVENTIONS: Anorectal manometry with a microtransducer. OUTCOME MEASURES: Maximal resting and squeeze pressures. Resting and squeeze pressure areas were calculated in the interval 0-5 cm from the anal verge. RESULTS: There was no difference in mean(SD) resting pressure (mmHg) between men (50(17)) and women (47(15)) but there was a significant difference in the mean(SD) resting pressure area (units) (149(46) compared with 125(46)). The squeeze pressure was significantly higher in men (193(57)) than in women (115(42), t = 7.72, p < 0.001). The difference between the sexes was even more pronounced when the squeeze pressure areas were compared: (624(216) and 318(114), respectively, t = 9.50, p < 0.001). CONCLUSION: Both the pressure values and the high pressure zone should be considered in the interpretation of the results of anorectal manometry. The pressure area includes both aspects and showed a greater separation between men and women than the peak pressure value alone. PMID- 8519878 TI - Torsion of an accessory spleen in an adult. Case report. PMID- 8519879 TI - Idiopathic rupture of the iliac vein. Case report. PMID- 8519880 TI - Chronic contained rupture of an abdominal aortic aneurysm complicated by infection and femoral neuropathy. Case report. PMID- 8519881 TI - Persistent mullerian duct syndrome and transverse testicular ectopia. PMID- 8519882 TI - Effect of directly ultraviolet-irradiated allografts of fetal pancreas in experimental diabetic dogs. AB - The proliferative responses of UV-irradiated islets from fetal pancreas decreased to 53.8 +/- 4.7% (mean +/- SEM) compared to that of UV-irradiated islets by allogeneic mixed islet-cell lymphocyte culture. In 5 pancreatectomized dogs, UV irradiated fetal dog pancreas was transplanted either into omentum pouches or the spleen without immunosuppressive agents. The diabetic status (daily insulin requirement for hyperglycemia, decrease in body weight, urine glucose) improved in dogs after allo-transplantation. The survival time after total pancreatectomy was significantly longer in allografted dogs than those treated only with daily insulin injections. PMID- 8519883 TI - Serum lipid and lipoprotein concentrations in obese dogs. AB - Serum lipid and lipoprotein concentrations in 10 obese and 16 control dogs were examined. The serum triglyceride (TG) concentration in obese dogs was significantly higher than in control dogs. The serum concentrations of TG and phospholipid (PL) in beta lipoprotein and PL in pre-beta lipoprotein were significantly higher in obese dogs, while the serum PL concentration in alpha 1 lipoprotein was significantly lower in obese animals. In the serum total cholesterol concentration in obese dogs, a higher tendency for beta and pre-beta lipoproteins and lower tendency for alpha 1 lipoprotein were observed. These abnormal lipoprotein profiles were similar to those in diabetes mellitus in men and acute pancreatitis in dogs. PMID- 8519885 TI - Detection of the chemotactic factor for canine peripheral blood mononuclear cells and polymorphonuclear cells in the culture supernatant of Cos7 cells transfected with canine interleukin-8 cDNA. AB - Chemotactic activities in the culture supernatants of Cos7 cells transfected with a cloned canine IL-8 cDNA (pcIL-8SR alpha 14) were evaluated by using mononuclear cells (MNC) and polymorphonuclear cells (PMN) from the peripheral blood of dogs. The culture supernatants of Cos7 cells were collected 66 hr after the transfection of pcIL-8SR alpha 14 (Cos7/cIL-8). Chemotactic activities in the culture supernatants for MNC and PMN were determined as migration distances in Millipore membrane filters in a modified Boyden's chamber method. Peroxidase staining for MNC was effective not only for cells in cytospun smears but also for cells migrated in the filters. PMN in cytospun smears were well stained by peroxidase staining, whereas migrated PMN in the filters were stained weakly. Chemotactic activities in the culture supernatant of Cos7/cIL-8 cells for both MNC and PMN were significantly higher than those of control Cos7 cells. In addition, the culture supernatant of Cos7/cIL-8 cells was chemotactic for peroxidase negative nonadherent MNC (lymphocytes), but not for peroxidase positive adherent MNC (monocytes). This Cos7/cIL-8 supernatant also showed chemotactic activities for neutrophils in a dose dependent manner. These results suggest that the culture supernatant of Cos7/cIL-8 is chemotactic for lymphocytes as well as for neutrophils. PMID- 8519884 TI - Enhancement of resistance to bacterial infection in mice by vitamin B2. AB - We found that the intramuscular injection of vitamin B2 enhanced host resistance to E. coli infection in a dose-dependent manner (6.25 mg/kg-100 mg/kg). Furthermore, VB2 exhibited the protective activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Actinobacillus pleuropneumoniae. The mechanism of action of VB2 for enhancing resistance in mice may be, at least in part, its ability to stimulate the multiplication of neutrophils and monocytes, and to activate macrophages. PMID- 8519886 TI - Antimicrobial activity of lasalocid against Selenomonas ruminantium--effect of changes in pH induced by changing glucose concentration. AB - A significant decrease in pH occurred in the culture medium when cells of Selenomonas ruminantium HD-4 were incubated in the presence of relatively high concentrations of glucose (0.4 and 1.0%). Forty microM lasalocid reduced cell growth to 35.5 and 35.7% of control growth, respectively, for 0.05 and 0.4% glucose, while growth was completely inhibited by 40 microM lasalocid in the presence of 1.0% glucose. In the presence of 80 microM lasalocid, cells were unable to grow within 24 hr at any glucose concentration. In the case of treatment with 10 microM lasalocid, growth was inhibited when pH decreased below 6.0 in the presence of 0.4 and 1.0% glucose. With 0.05% glucose, pH never reduced to below 6.4 within 24 hr and there was no significant effect of lasalocid on either growth or pH. When cultures were treated with 10 microM lasalocid at the mid-exponential phase, growth was moderately inhibited and abnormal cells which had outer membrane detached from the inner membrane layer resulting in cell lysis were found in thin sections. These results indicate that the presence of large amounts of glucose decreases pH in culture medium and that the decrease in pH to below about 6.0 causes the increased effect of lasalocid on the growth of S. ruminantium. These results suggest that the antimicrobial activity of lasalocid is potentiated by a decrease in extracellular pH. PMID- 8519887 TI - Comparison of the requirement of porcine peripheral blood monocytes and intestinal lamina propria macrophages as accessory cells in primary allogeneic mixed leukocyte responses and oxidative mitogenesis. AB - Differences and/or similarities of the accessory cell activity of circulating peripheral blood monocytes (PBM) and intestinal lamina propria macrophages (LPM) in the pig have never been evaluated. Therefore this study was designed to compare the accessory cell activity of these cells in the induction of primary allogeneic mixed leukocyte responses (MLR) and polyclonal mitogenesis. Splenic adherent cells (SPAC) were used as control accessory cells. It was observed that PBM, LPM and SPAC induced significant T cell proliferation in response to allo antigens. Significantly higher responses were elicited by SPAC, followed by PBM whereas, LPM induced low responses when cultures were established a T cell: accessory cell ratio of 1:1. PBM was the only accessory cell which induced significant responses at a cell ratio of 10:1. Whereas LPM and SPAC were able to induce significant oxidative mitogenesis, PBM were poor stimulators of this response. The observed difference between PBM, SPAC and LPM is attributed partly to differences in number of major histocompatibility complex (MHC) class II positive cells and the intensity of expression of the glycoproteins. PMID- 8519888 TI - Changes in lectin binding patterns of chick primordial germ cells and Sertoli cells during sexual differentiation. AB - The distribution and properties of sugar residues in germ and Sertoli cells of differentiating chick gonads were examined by light microscopy using twelve different lectins. Characteristics binding patterns of ConA, RCA-1, BPA, WGA and STA were observed in germ and Sertoli cells during testicular development. BPA preferentially bound to the cytoplasm and plasma membrane of primordial germ cells (PGCs). BPA reaction appeared prior to stage 29, continued until stage 36, and completely disappeared at stage 37. This finding indicates that dynamic changes in glycoconjugates containing N-acetyl-D-galactosamine residues may occur in the cytoplasm and plasma membrane of PGCs. During the formation of testicular cords (stages 36-39), ConA, WGA, STA and RCA-I also showed a positive reaction on the cell surface of differentiating Sertoli cells. Therefore, these glycoconjugates on Sertoli cell surfaces may play an important role in testicular cord formation. PMID- 8519889 TI - Experimental infection of pigs with a parvovirus isolated from the diarrheic feces of a pig. AB - A parvovirus (the H-45 strain) isolated from an outbreak of epizootic diarrhea in swine was examined to observe the infectivity and pathogenecity in swine. The virus infection by intranasal route was demonstrated in each group of 2- and 5 day-old colostrum-deprived pigs, 30- and 100-day-old pigs by virus recovery from the nasal and rectal swabs, and detecting seroconversion. The virus was recovered from rectal swabs up to 14 days after inoculation and from nasal swabs up to 9 days. Uninoculated pigs were infected with the virus by contacting with the inoculated pigs. Between 1 and 5 days after inoculation, the inoculated pigs of 2, 5 and 30 days old developed diarrhea and then all the pigs of 2 days old died, resulting from dehydration. In the pigs died after intranasal inoculation, the virus was recovered mainly from the respiratory and gastrointestinal tracts. One hundred-day-old pigs showed no clinical signs. The pathological change was characterised by congestion and edema with hemorrhage in the epithelium of the small intestines exhibiting additional degeneration and desquamation of the epithelial cells. PMID- 8519890 TI - Effect of extracellular matrix on two cell lines established from Mongolian Gerbil's (Meriones unguiculatus) malignant melanoma. AB - We investigated the effect of extracellular matrix (ECM) on the adhesion, morphology and proliferation of two Mongolian gerbil's melanoma cell lines (MGM S, MGM-A) which differed in malignancy. Fibronectin matrix was detected on the cell surface of MGM-S by immunofluorescence techniques. MGM-A cells, showing a multipolar shape, were widely spread over the dishes coated with fibronectin, laminin or type IV collagen. The adhesion rate of MGM-A cells to ECM components was higher compared to that in controls. Attachment to laminin was conspicuously promoted. The effect of laminin on MGM-A cell growth was also the highest among the substrates examined. On the other hand, these ECM components did not affect MGM-S cells. These results suggest that laminin and fibronectin may participate in the malignancy of MGM cell lines. PMID- 8519891 TI - Early embryonic development in vitro and embryo transfer in the cat. AB - Ten female cats were given a total dose of 200 IU PMSG over 3 days to induce superovulation. One to four-cell stage embryos were collected by flushing the oviducts 48 to 54 hr after the initial 250 IU dose of hCG. Some of the normal embryos collected were examined for culture in Medium-199 supplemented with 20% FCS. After 72 hr of culture, 222/248 (89.5%) had developed to the morula stage, and by 96-168 hr, 110 (64.7%) out of 170 morulae had developed into blastocysts. Four to 12 embryos cultured in vitro per cat were transferred to one of the uterine horns of 12 recipients in which synchronous ovulation had been induced with hCG. All 4 recipients of embryos which had developed to the morula stage on culture day 3, 3 of the 5 recipients of blastocysts on culture days 4-6, and none of the 3 recipients of blastocysts on culture day 7 became pregnant. It is concluded that early feline embryos are capable of efficiently developing into transferable morulae in vitro by ordinary culture methods, but that there is partial developmental arrest from the morula to the blastocyst stage. PMID- 8519892 TI - Efficacy of subcutaneous application of live infectious bursal disease vaccine in young chickens with maternally derived antibody. AB - The infectivity of neutralized IBDV by normal chicken serum (NCS) was detected in day-old and 3-week-old chicken spleen adherent (CSA) cells, and that of neutralized IBDV by maternal antibody (MN-Ab) was detected in 3-week-old CSA cells. Moreover, CSA cells from day-old chickens had complement receptor (CR), and CSA cells from 1-week-old had both CR and Fc receptor (FcR). However, the infectivity of neutralized IBDV by MN-Ab was confirmed on CSA cells which were blocked for FcR on CSA cells by heat-aggregated NCS (56 degrees C, 60 min). These results indicated that infection of neutralized IBDV by NCS on CSA cells occurred via CR, and neutralized IBDV by MN-Ab was infected via FcR. In day-old specific pathogen free (SPF) chickens, the antibody level in NCS treated and non-treated IBD live vaccine subcutaneously inoculated groups was higher than the levels in the MN-Ab-treated IBDV inoculated group, and detected until 28 days old. Moreover, subcutaneously inoculated chickens were protected against the challenge of wild IBDV at 21 days old, whereas subcutaneously inoculated chickens were infected with MN-Ab-treated IBD live vaccine. In commercial layers which had MN Ab, antibody levels of subcutaneously vaccinated group were higher than both the non-vaccinated and orally vaccinated groups, and virus isolation and viral antigen were positive with high detection rates on peripheral lymphocytes of each subcutaneously vaccinated group of SPF and commercial chickens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519893 TI - Disinfestation of experimentally infested cat fleas, Ctenocephalides felis, on cats and dogs by oral lufenuron. AB - In vivo efficacy of orally administered lufenuron, an insect growth regulator, in disinfesting cat fleas was evaluated, using flea-free cats and dogs which were purchased and infested every 10 days with cat fleas from a colony kept in our laboratory. Lufenuron was orally administered as a single dose of 15, 30, or 60 mg/kg to cats, and 5, 10 or 20 mg/kg to dogs. In cats, adult flea emergence was intensively prevented for 30 days by dosing of 15 mg/kg of lufenuron and 40 days by 30 or 60 mg/kg. The average egg hatch rate in 15 mg/kg group was, however, significantly higher than those in 30 mg/kg or more, suggesting necessity to dose 30 mg/kg to cats to prevent development of cat fleas effectively. In dogs, a lower dose of the drug, 10 mg/kg seemed to be sufficient for the complete prevention of flea development. PMID- 8519894 TI - Sex steroid levels throughout gestation in cows carrying normal and malformed fetuses. AB - Birth of malformed/stillborn calves is a liability to farmers and diagnosis of the condition early in gestation would be of immense economic benefit. We report on peripheral plasma progesterone (P4), estrone (E1) and estradiol (E2) concentrations quantified by radioimmunoassay throughout gestation in twin embryo recipient cows carrying normal (cow N), freemartin(cow F) and schistosomus reflexus fetuses (cow S). The undulating plasma P4 profiles were identical in all three cows throughout gestation apart from that the concentration in cow F dramatically declined on day 254 and it subsequently gave birth to stillborn calves. The plasma E1 concentration progressively increased in cow N to peak at parturition and then rapidly declined a day after parturition. E1 levels were lower in cow F than in cow N and exhibited a sudden increase in concentration at day 254 of gestation followed by a dramatic decline. Cow S had lower E1 levels throughout gestation than cow N and showed an undulating profile. The plasma E2 profile paralleled the plasma E1 profile in all the cows but the E2 concentration throughout gestation was lower than the E1 levels. Plasma E1 and E2 levels declined to < 20 pg/ml in cow N a day after parturition as opposed to > 150 pg/ml E1 and > 20 pg/ml E2 levels, respectively, in cows F and S. Our results indicate that E1 and E2 are better than P4 as prognostic indicators of fetal in-utero status as well as the number of fetuses a cow is gestating. PMID- 8519895 TI - Development and physiological degradation of tooth buds and development of rudiment of baleen plate in southern minke whale, Balaenoptera acutorostrata. AB - The development and degradation of temporary tooth buds and the development of rudiment of baleen plate were observed by gross-anatomical and histological examinations in twenty-four fetuses of the southern minke whale, Balaenoptera acutorostrata. The primary patterns of development of tooth buds were similar to those of deciduous tooth buds in the terrestrial species. Degradation of tooth buds was observed in the fetuses more than 615 mm body length (BL) and might proceed throughout the dental surface of the tooth buds. That degradation pattern was a little different from that of deciduous tooth buds in terrestrial species, which has a limited degradation area at the root of the tooth buds. In the fetuses with 135 and 153 mm BL, the upper jaw had a larger number of tooth buds than the lower jaw, although the number of buds varied in different individuals. Formation of rudiment of baleen plate was observed with degraded tooth buds in the fetus of 903 mm BL and it may be induced by the degradation of tooth buds. PMID- 8519896 TI - Morphological, serological and antigenic characteristics, and protein profile of newly isolated Japanese bovine Babesia parasite with particular reference to those of B. ovata. AB - An intraerythrocytic large protozoan, tentatively designated Babesia sp. 1, was recently isolated from cattle in Hokkaido Prefecture, Japan. This parasite closely resembled B. ovata in shape of piroplasms, but was distinguishable by other morphological, immunological, and biochemical characters. The paired pyriform piroplasm of B. sp. 1 was larger than that of B. ovata. The results from serological and antigenic examination by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis showed that there were cross- but distinguishable-reaction between B. sp. 1 and B. ovata. Protein profiles of both Babesia parasites piroplasms analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) were apparently different from each other. Several major proteins revealed by 2D-PAGE and the immunodominant proteins resolved by Western blot analysis (40 kDa for B. sp. 1 and 29 kDa for B. ovata) were unique to each parasite. The results of the present study indicate the possibility that B. sp. 1 is a species different from B. ovata. PMID- 8519897 TI - Enhanced replication of orbiviruses in bovine testicle cells infected with bovine viral diarrhoea virus. AB - Bovine testicle (BT) cells infected with non-cytopathogenic (NCP) bovine viral diarrhoea virus (BVDV) developed cytopathogenic effect (CPE) after superinfection with 7 Orbiviruses, whereas no CPE was induced by them in the absence of NCP BVDV infection. The CPE was accompanied by the enhanced replication of Orbiviruses. Seven of 10 strains of NCP BVDV induced the enhanced replication of Ibaraki virus, a member of Orbivirus. These 7 strains of NCP BVDV were END phenomenon positive. In contrast, the absence of CPE and the suppression of growth of Ibaraki virus were seen in BT cells infected with the other 3 strains which were END phenomenon negative. The END phenomenon negative viruses were different markedly from the END phenomenon positive viruses with respect to interactions with Orbivirus. The mechanism of the enhanced replication of Orbivirus seems to be explained with the suppression by the END phenomenon positive NCP BVDV to the interferon production of Orbivirus in BT cells. PMID- 8519898 TI - Hypersensitivity to Japanese cedar (Cryptomeria japonica) pollen in dogs. AB - Four of 51 dogs with chronic dermatitis were made to react to crude Japanese cedar (Cryptomeria japonica, CJ) pollen allergen by the intradermal skin test (IDST). These four dogs had specific IgE to CJ as determined by Prausnitz-Kustner test. In the provocation test, nasal discharge increased 5 to 20 min after introduction of the crude CJ pollen allergen into the nasal cavities, in two of three dogs. These results demonstrated that these dogs had hypersensitive to CJ pollen, which might be a cause of atopic disease in dogs. PMID- 8519899 TI - Effects of enriched and impoverished housing environments on the electrocorticograms (ECoGs) of middle-aged rats. AB - Electrocorticograms (ECoGs) were evaluated in young rats and in middle-aged (19 months) rats housed under three different environments. The standard condition (SC, N = 5) indicated the condition where two rats stayed in a standard cage, enriched condition (EC, N = 5) meant keeping 6-8 rats in a large cage and impoverished condition (IC, N = 5) was referred to as housing a single rat in a small cage. All middle-aged rats were kept under one of these cage conditions for 12 months, starting at 7 months of age. An ECoG was recorded simultaneously from 6 different locations on the scalp and was subjected to comparisons among the SC, EC and IC by means of spectral analysis. The power of the occipital alpha band (8.1-10.0 Hz) was significantly increased in IC rats. Total occipital power in IC rats was also enhanced as compared to SC and EC rats. These findings demonstrate that ECoG changes are present in the neocortex of middle-aged rats in different environments. In addition, social interaction seems to have a stronger effect than the differences in living capacity. These results indicate that the aging process should be studied from the viewpoint of environmental influences. PMID- 8519900 TI - Congenital anophthalmia with caudal vertebral anomalies in Japanese Brown cattle. AB - Anophthalmia and caudal vertebral anomalies such as taillessness or wry tail were morphologically examined in ten Japanese Brown calves obtained in Kumamoto Prefecture. The anomalous calves lacked eyeball bilaterally or unilaterally but had small-sized eyelids and narrow palpebral fissures. A small cystic, solid or spot-like remnant of eyeball (REB) was buried in the mixture of vestigial extraocular muscles, lacrimal gland and adipose tissue of the orbit. The REB was composed of irregularly arranged elements of ocular wall such as sclera, choroid and retina. The retina was often dysplastic and connected to the hypoplastic optic nerve. These morphological changes might represent the defective processes after the formation of the optic vesicle or cup. Therefore, this eye defect may be defined as degenerative anophthalmia. The defects of the vertebral body such as wedge vertebra, hemivertebra, and sagittal cleft vertebra seen in the lumbar, sacral, and coccygial regions and the meandering of the axial line of abnormal vertebrae may suggest the failure of notochord formation in the early fetal period. From the embryological point of view, it seemed possible that the calves were exposed to teratogen at the critical time of optic organogenesis and notochordal formation. The cause of anomalies could not be determined in this study. PMID- 8519901 TI - The effect of hypovolemic shock and reperfusion on the hepatic oxygen supply uptake relationship in the dog. AB - The hepatic oxygen supply-uptake relationship was investigated during hypovolemic shock using a right heart bypass technique. The results were dissimilar to those previously reported in that the ratio of liver oxygen delivery to systemic oxygen delivery was significantly decreased during shock. The decreased ratio was due to a significant decrease in the portal venous oxygen delivery when compared to the decrease in the systemic oxygen delivery. The decrease in portal venous oxygen delivery was caused not only by the decrease in portal venous blood flow, but also by the decrease in oxygen content of portal blood. The ratio of hepatic arterial oxygen delivery, on the other hand, was significantly increased during shock. Hypovolemic shock increased the liver oxygen extraction ratio to nearly 100% of the pre-shock value. These findings suggest a hepatic protective mechanism for matching oxygen uptake to rising hepatic oxygen requirements. Liver oxygen delivery returned to pre-shock value after correction of hypovolemia primarily due to a significant increase in hepatic arterial oxygen delivery. A significant negative correlation between the liver oxygen extraction ratio and the oxygen content of hepatic venous blood was observed. The hepatic venous oxygen content appears to be a simple and appropriate index of liver oxygenation in clinical medicine because it is difficult to evaluate the liver oxygen extraction ratio directly. PMID- 8519902 TI - Effects of hypovolemic shock and reperfusion on liver blood flow in the dog. AB - Liver blood flow was investigated in hypovolemic shock using a modified right heart bypass technique which can obtain accurate portal blood flow. Findings were similar to those previously reported: hepatic blood flow accounted for 34% of cardiac output in this study; 76% of hepatic blood flow was delivered from the portal vein and 24% from the hepatic artery. Hypovolemic shock markedly decreased total liver blood flow by a reduction in portal venous blood flow. The findings of this study provide evidence that mesenteric blood flow is a peripheral circulation circuit where blood flow is restricted during reduced circulatory volume. Development of a hepatic arterial buffer response during hypovolemic shock was confirmed by an increased ratio of hepatic arterial flow to cardiac output. Reduced total hepatic blood flow during hypovolemic shock returned to control flow by an increase in hepatic arterial flow after reperfusion. The results of this study demonstrate that compensated reactions for maintaining liver blood flow mainly due to the hepatic arterial buffer response were functioned both during hypovolemic shock and after elimination of shock. PMID- 8519903 TI - Construction of the recombinant feline herpesvirus type 1 deleted thymidine kinase gene. AB - We constructed a recombinant virus containing defined deletion within thymidine kinase (TK) gene from feline herpesvirus type 1 (FHV-1) C7301, which was isolated in Japan, by standard rescue procedures with thymidine arabinoside (araT) selection. The araT resistant recombinant virus was designated as C7301dlTK. Southern blot analysis, together with polymerase chain reaction, revealed a deletion with the expected size, based on agarose gel electrophoresis, of the TK gene region in the C7301dlTK. Growth kinetics of the C7301dlTK in CRFK cells was similar to that of ther parent C7301 that possesses TK activity. However, plaques produced by the C7301dlTK were significantly smaller than those of the parent virus. This report migth be applicable for the development of a new genetically engineered FHV-1 vaccine. PMID- 8519904 TI - Pathogenicity of Corynebacterium kutscheri in the Syrian hamster. AB - The pathogenicity of Corynebacterium kutscheri isolated for the first time from Syrian hamster was experimentally studied in hamsters. In hamsters given intramuscular (i.m.) or subcutaneous (s.c.) inoculation with 10 or 10(3) bacteria, neither clinical signs nor gross lesions were found. In those given 10(5) bacteria i.m., moderate proliferation of granulation tissue was found in the muscle of the inoculation region at necropsy. In the animals given 10(5) bacteria s.c., a nodular lesion was observed at the inoculation site 2 days post inoculation (p.i.), but the nodules subsided gradually from 6 days p.i. and were unclear 10 days p.i. At necropsy, small abscesses were found in all the animals in this group. In those given 10(7) bacteria either i.m. or s.c., lesions were clearly observed at the inoculation site 1 to 10 days p.i., and a large abscess was noted at necropsy. The organisms were isolated only from the lesions in the groups. Agglutinating antibody in the sera was detected only in the animals given 10(5) or 10(7) bacteria. This suggests that 10(5) of C. kutscheri are needed to form localized nodular abscesses in Syrian hamsters. PMID- 8519905 TI - Application of anti-bovine CD2 monoclonal antibody to the rosette inhibition test for detection of early pregnancy factor in cattle. AB - To reliably detect early pregnancy factor (EPF) in cattle, monoclonal antibody specific for bovine CD2 molecule, which is the sheep red blood cell (SRBC) receptor on bovine T cell surface, was applied to the rosette inhibition test. The rosette inhibition titers (RITs) were significantly higher in pooled sera from early pregnant cattle than in those of non-pregnant cattle using two anti bovine CD2 monoclonal antibodies, B26A4 (P < 0.001) and BAQ95A (P < 0.01). The dissociation value of RITs between pregnancy and non-pregnancy with B26A4 was greater than that with BAQ95A. The B26A4 monoclonal antibody was therefore applied to the rosette inhibition test in subsequent experiments. The RITs in serum of individual pregnant and non-pregnant cows 8 days after estrus were significantly different (P < 0.001) by three or more dilutions. When the rosette inhibition test was carried out in sera from individual pregnant and non-pregnant cows at estrus and at 24, 72 and 168 hr after ovulation, the RITs of pregnancy sera increased significantly at 24 hr after ovulation as compared with non pregnancy sera (P < 0.001). These results indicate anti-bovine CD2 monoclonal antibody can be utilized with the rosette inhibition test to detect EPF in cattle, and that this assay detects bovine EPF for pregnancy serum at least 24 hr after ovulation. PMID- 8519906 TI - Protective efficacy of cell-free-antigen of Actinobacillus pleuropneumoniae in mice. AB - Cell-free-antigen (CFA) vaccines of strain Y-1 (serotype 1), G-4 (serotype 2) and E-3 (serotype 5) of Actinobacillus pleuropneumoniae (A. pleuropneumoniae) were prepared by emulsifying concentrated culture supernatant with oil-adjuvant. Mice immunized with the CFA vaccine had a high survival rate (90-100%) against challenge with the homologous strain. They also had cross-protective activity against challenge with the heterogeneous strains but their survival rate was low (20-50%). On the other hand, mice immunized with whole cell vaccine showed serotype specific protection and only a little cross protection. The protective antigens of the CFA were investigated. MAbs were produced by the standard method using spleen cells of mice immunized with CFA. MAbs to Apx I, II, III and capsular antigen of serotype 5 were obtained. Only MAbs to Apx I showed hemolysin neutralization activity among them. The protective effect of these MAbs against A. pleuropneumoniae infection were examined by passive immunization. Administration of Apx I MAb to mice extended survival time after challenge with serotype 5. The mice showed partial cross-protection against challenge with serotype 1. Survival rate was considerably low after the challenge infection. None of the mice given MAbs to Apx II or III were protected against challenge with serotype 5. The mice given MAb to capsular antigen of serotype 5 had a high survival rate (70%) against a challenge with a homologous serotype. Furthermore, mice given MAbs against Apx I and capsular antigen of serotype 5 were completely protected against a challenge with A. pleuropneumoniae serotype 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8519907 TI - Ultrastructural changes in fat cells and blood capillaries of the mammary gland in starved mice. AB - The effects of starvation on fat cells and blood capillaries of the first abdomino-inguinal mammary gland in mice were investigated by light and transmission electron microscopy. The body weight of starved mice abruptly decreased to approximately 70% of that of controls at 3 days of starvation and, thereafter, gradually decreased. In adipose tissues of mammary stroma, multilocular fat cells increased in number and clustered during starvation to a glandular appearance at 6 days. Collagen fibers increased in amount around mammary ducts and buds. By electron microscopy, multilocular fat cells possessed numerous mitochondria, small lipid droplets, and plasmalemmal vesicles, while endothelial cells of the blood capillaries showed numerous pinocytotic vesicles plus short marginal folds and microvillous processes. These observations prove that the number of pinocytotic vesicles in blood capillary endothelium is closely related with the increased amount of lipid of fat cells in the mammary gland during starvation. PMID- 8519908 TI - The relationship between serum lipoprotein levels and marbling of muscle tissue in beef cattle. AB - The relationship between serum lipoprotein levels and the grades of marbling in muscle tissue was analyzed by gel filtration of lipoprotein fraction obtained from sera of 80 Japanese black beef cattle in the final stage of fattening. It was found that the increase in the Beef Marbling Standard number was positively correlated with the concentration of low-density lipoprotein cholesterol (r = 0.79) and negatively with that of high-density lipoprotein cholesterol (r = 0.47). PMID- 8519909 TI - Isolation of a serotype G6P11 bovine rotavirus showing two-way cross neutralization with the serotype G10P11 virus. AB - Four stains designated as OB94-1 to OB94-4 of group A bovine rotavirus (BRV) were isolated from 35 fecal samples of calves with diarrhea in sporadic outbreaks. In VP7 (G) and VP4 (P) serotyping of these isolates, OB94-1 to OB94-3 were determined as G6P5, G6P5 and G10P5, respectively, by cross neutralization (NT) test and the G- and P- serotyping polymerase chain reaction (PCR) analysis. OB94 4 showed a one-way antigenic relation with the Lincoln stain (G6P1) and a weak antigenic relationship with the KK3 strain (G10P11), and was determined as G6P11 by the PCR method. Thus, OB94-4 was shown to be a new G6 BRV with different antigenic properties from the others in the NT test. PMID- 8519910 TI - Partial purification and some properties of a neutral proteinase in rat ovary. AB - The ovary of rat possessed a neutral proteinase which had an optimum pH at around 8.5 in the presence of 0.5 M NaCl. The proteinase was soluble only in media of high ionic strength such as 2 M NaCl. In order to prevent the reprecipitation in media of low ionic strength of the enzyme solubilized, it is necessary to add protamine sulfate to the solubilizing medium. When the solubilized enzyme was applied to a Sephadex column, the proteinase activity was eluted at the same position as bovine alpha-chymotrypsinogen. The results using some protease inhibitors showed that the proteinase was a chymotrypsin-like serine enzyme. When rats were treated with compound 48/80, the proteinase activity almost completely disappeared, suggesting that the enzyme is of mast cell origin. PMID- 8519911 TI - Canine plasma erythropoietin levels in 124 cases of anemia. AB - Erythropoietin (EPO) levels in plasma from 124 clinically anemic dogs were determined by in vivo bioassay. In 81 anemic dogs with normal renal function, the concentration of plasma EPO showed a close correlation with the hemoglobin concentration. The plasma EPO level was obviously decreased in 43 anemic dogs with renal failure. Of these dogs with renal failure, 17 showed no detectable plasma EPO and resulted in the death of these dogs. In the remaining 26 dogs having detectable plasma EPO, the plasma concentration rate of EPO related to blood urea nitrogen and serum creatinine values. PMID- 8519912 TI - Effect of platelet activating factor antagonist (TCV-309) on lung injury in dogs with experimentally endotoxin-induced shock. AB - The effect of TCV-309, a newly developed platelet activating factor (PAF) antagonist, on the wet/dry weight ratio of the lung (index of pulmonary edema) and the pulmonary surface activity (index of pulmonary compliance) was evaluated in comparison with that of CV-3988 (PAF-antagonist). Administration of TCV-309 (1 mg/kg) or CV-3988 (10 mg/kg) significantly reduced the wet/dry weight ratio which was increased by endotoxin administration (3 mg/kg). It also augmented the pulmonary surface activity. Administration of either TCV-309 or CV-3988 alleviated the histologic lesions caused by endotoxic shock. These results suggest that lung injury during endotoxic shock can be controlled by TCV-309 as by CV-3988. PMID- 8519913 TI - Cell counts in peripheral blood and bone marrow of male CBA/N mice. AB - Measurements for blood and bone marrow cell counts were carried out in male CBA/N mice aged 3, 6, 9, 12, and 26 weeks and the values were compared with those in normal mice. In the peripheral blood, CBA/N mice showed decreasing numbers of leukocytes with age, without marked changes in the differential cell count. In the bone marrow of CBA/N mice, the total number of femoral bone marrow cells was low in later life (26 weeks of age), and differential cell counts revealed a high granuloid/erythroid ratio at 3 weeks of age due to a low erythroblast count. PMID- 8519914 TI - Serotypes and antimicrobial susceptibility of Actinobacillus pleuropneumoniae isolated from piglets with pleuropneumonia. AB - Minimal inhibitory concentrations (MICs) of 20 antimicrobial agents were determined for 67 field strains of Actinobacillus pleuropneumoniae isolated from the lungs of piglets with pleuropneumonia during the period 1992 to 1994, in Japan. Of these 67 strains, all 29 strains that were identified as serotypes 1 and 7 were resistant to chloramphenicol and tiamphenicol, whereas all of those identified as serotypes 2, 5 and 8 were susceptible to these antibiotics. Furthermore, 20 of 23 streptomycin-resistant strains were serotype 1, while, only 3 strains were serotype 2. These results suggest that the different serotypes of A. pleuropneumoniae vary in terms of antimicrobial-resistance. PMID- 8519915 TI - Serological survey of canine distemper virus infection using enzyme-linked immunosorbent assay. AB - For detection of antibodies against canine distemper virus (CDV), an enzyme linked immunosorbent assay (ELISA) was developed using a crude extract from cells infected with the Onderstepoort strain of CDV as antigen. Twenty-six sera from dogs experimentally vaccinated with the Snyder-Hill strain of CDV were compared by ELISA and a standard virus neutralization (NV) test. Since a good correlation between the titers obtained by both tests was observed, ELISA was considered to be a rapid and reliable method for a serological survey of CDV infection. When a total of 167 sera from dogs suspected of canine distemper under natural conditions were examined by the ELISA, 29 of the sera (17%) were found to have low VN antibody titers and high ELISA titers. The reason for the discrepancy in the titers was discussed. PMID- 8519916 TI - Effects of chitosan on experimental abscess with Staphylococcus aureus in dogs. AB - An abscess was developed experimentally by a subcutaneous inoculation of Stapylococcus (S.) aureus T-6 with a 4-cm silk suture in dogs. After draining the pus, the abscess was treated with a suspension of finely granulated chitosan (chitosan group), ampicillin (ampicillin group), or saline (control group) (Day 0). The chitosan group was further divided into 3 subgroups (0.01, 0.1, and 1.0 mg/subgroups). Similar treatment was repeated after 4 days (Day 4), followed by euthanasia on Day 8. The wound cavity contraction rate was calculated by measuring the wound cavity diameter by a sound on Days 0, 4 and 8. The wound cavity contraction rate was significantly higher in the ampicillin, 0.1 mg chitosan, and 1.0 mg chitosan groups than in the 0.01 mg chitosan and control groups on Days 4 and 8 (p < 0.05). In the 0.1 and 1.0 mg chitosan groups, the abscess healed completely in 6 out of 11 (55%), and 9 out of 10 cases (90%), respectively, by Day 8. In the ampicillin group, 4 out of 10 cases (40%) healed completely by Day 8. No healing occurred in the 0.01 mg chitosan and control groups. Histologically, the granulation tissue formed had abundant vascularization in the 0.1 and 1.0 mg chitosan groups on Day 8. PMID- 8519917 TI - Rapid detection of mycoplasma contamination in cell cultures by enzymatic detection of polymerase chain reaction (PCR) products. AB - Enzymatic detection of polymerase chain reaction (ED-PCR) was applied for rapid and easy identification of mycoplasmas from contaminated cell culture. This method was based on the capture of amplified products via biotin-streptavidine affinity and the detection of an incorporated hapten in amplified products with enzyme-linked antibody. Primers corresponding to common sequence of Mollicutes in 16S ribosomal RNA dominated gene was used. Nineteen of twenty Mollicutes so far reported as cell contaminants appeared positive by ED-PCR, whereas remaining one, Acholeplasma axanthum, appeared negative. Samples from sixty-two cell culture were tested for contamination of mycoplasmas by means of ED-PCR, cultivation, and electronmicroscopy. The results of ED-PCR were the same as those of cultivating method. The time required for all the detection process in ED-PCR was about 5 hr for 20 samples. We suggest that ED-PCR can be used in the rapid detection of mycoplasms from cell culture. PMID- 8519918 TI - Prevalence of antibodies to type A influenza viruses in swine sera 1990-1994. AB - A total of 3,120 swine sera collected for the years 1990-94 were tested for the presence of hemagglutination-inhibition (HI) antibodies against swine (H1N1) and human (H1N1 and H3N2) strains of influenza virus. No HI antibody against the swine strains was recognized during 18 months, though a slight prevalence (1.5 9.2%) of the antibodies was observed over the entire period. A wide variance in the incidence (0-26.3%) of antibodies against the human H3N2 strains was observed among the swine population. PMID- 8519919 TI - An outbreak of goose parvovirus infection in Japan. AB - In a Muscovy duck breeding-growing farm in Aomori prefecture, most of ducklings hatched during spring in 1994 died within two-week-old. The mortality was nearly 100%. In most cases, birds died without clinical signs and some with leg weakness. By serological and virological tests, the outbreak was identified as a goose parvovirus infection. In pathological test, however, no typical manifestations of goose parvovirus infections (hepatitis and intranuclear inclusion bodies in hepatic cells) were detected. PMID- 8519920 TI - Biphasic immune responses of cats under controlled infection with a feline enteric coronavirus-79-1683 strain. AB - Kittens inoculated orally with 10(2) PFU of feline enteric coronavirus developed no antibody to the virus despite the repeated challenges. However, they developed antibody for a long period with 5 x 10(3)-1.6 x 10(5) (mean 3 x 10(4)) and with 2.5 x 10(3)-2 x 10(4) (mean 6 x 10(3)) immunoperoxidase antibody titer when they were challenged with 10(5) and 10(3) PFU of virus following previous challenges, respectively. Viremia was found when kittens were inoculated with 10(5) PFU of virus, but not with 10(3) PFU of virus. The dose of 10(3) PFU of virus seemed to be a lower limit to establish infection. These results indicate that local infection induces a low antibody response and systemic infection induces a high antibody response. PMID- 8519921 TI - Quantitative measurement of canine renal arterial blood flow using Doppler ultrasonography. AB - The aim of this study was to estimate the accuracy of the quantitative measurement of renal blood flow using the non-invasive method, Doppler ultrasonography. First, we determined a method of approach to the renal artery in order to detect the rate and pattern of flow, using 8 adult beagles under general anesthesia. Secondly, we examined the renal arterial blood flow using the Doppler method and electromagnetic flowmeter using 7 mongrel dogs. A significant correlation (r = 0.879; p < 0.01) was found between two methods, though the Doppler system tended to indicate high values than the electromagnetic flowmeter. Our study suggests that the Doppler method is a useful non-invasive technique of measuring renal blood flow in the dog. PMID- 8519922 TI - Determination of butyltin metabolites in the mouse liver by flameless atomic absorption spectrophotometry. AB - A new analytical method for observation of the metabolic status of butyltin compounds in the mouse liver was devised by a combination of extraction, purification and separation followed by quantitative analysis of each butyltin compound. After the extraction of all tin compounds from liver homogenate with ethyl acetate, these compounds were purified by combination of the fractional extract with organic solvents and column chromatography. The purified fraction was also analyzed by thin-layer chromatography, identifying each tin compound from differences in mobility on a silica gel plate. The tin content in the each separated spot on the plates was measured by flameless atomic absorption spectrophotometry after extraction by acid treatment. About 90% of tin was recovered by this method from the liver of mice which had been administered tri- or dibutyltin compound orally. This method will be useful for quantification of each metabolic product formed from butyltin compounds in vivo. PMID- 8519923 TI - A retrospective serological survey of the encephalomyocarditis virus among pigs in Chiba prefecture, Japan. AB - One thousand two hundred and forty pigs' sera collected from 1975 to 1992 on 240 farms in Chiba prefecture were subjected to a neutralization test for the encephalomyocarditis (EMC) virus. Seven (23.3%) of 30 pigs in 1975 had neutralizing antibodies against the EMC virus. The antibody positive rates each year ranged from 16.7% (1976) to 56.3% (1981). The differences of antibody positive rates between districts were not great after 1985. These serological results suggested that the EMC virus infection had already been introduced by 1975 and that it is prevalent among pigs in Chiba prefecture. PMID- 8519924 TI - Congenital lymphedema in a calf with lymph node dysplasia or aplasia. AB - A 9-month-old male Japanese Black calf with subcutaneous edema in mainly both limbs was investigated. Necropsy revealed about 20 l of ascites and severe edema in the large omentum, abomasal folds, conjunctiva and rectum. Only small internal iliac and hepatic lymph nodes were found. Histopathology revealed lymph node dysplasia showing excess trabecular formation, reticular cell proliferation, and obvious dilation of both afferent and efferent lymphatics. These findings suggest that disturbance of lymphatic flow with congenital lymph nodes dyspalsia or aplasia resulted in lymphedema in this calf. PMID- 8519925 TI - Self-reinforced composite poly(methyl methacrylate): static and fatigue properties. AB - A novel material called 'self-reinforced composite poly(methyl methacrylate)' (SRC-PMMA) is described. This composite material consists of high strength, high ductility PMMA fibres embedded in a matrix of PMMA. Tensile tests, three-point flexural tests, fracture toughness tests and flexural fatigue tests were carried out on unidirectional continuous fibre SRC-PMMA materials. Commercial sheet PMMA and bone cement were also tested for comparison purposes. Two PMMA fibre sizes (40 and 120 microns diameters) with different mechanical properties were used to make the SRC-PMMA materials. The results of this study show that the tensile strength, tensile modulus and tensile strain-to-failure were significantly greater for the SRC-PMMA compared with commercial PMMA (P < 0.05). The flexural strength was not increased in the SRC-PMMA compared with PMMA alone but was greater than that in bone cement (P < 0.05). There were no differences in flexural modulus between any group. The flexural strain-to-failure (30-35% for SRC-PMMA) was about three times greater in SRC-PMMA compared with bone cement and PMMA. Fracture toughness of these SRC-PMMA materials was also significantly greater than PMMA and bone cement (P < 0.001). Fracture toughness values of 3.2 MPa m1/2 were found in the 40 microns SRC-PMMA compared with 2.3 MPa m1/2 for the 120 microns SRC-PMMA and 1.3 MPa m1/2 for PMMA and bone cement. The fatigue strength of both SRC-PMMA samples was significantly greater (P < 0.001) at 80 MPa (10(6) cycles) compared with bone cement and PMMA, both of which had fatigue strengths of about 18 MPa. Fatigue damage in the form of fibre splitting and fibre-matrix interface failure was observed in the SRC-PMMA samples while the PMMA and bone cement showed only smooth fractures. During cyclic fatigue testing, the ongoing damage processes were periodically monitored using several novel computer-based and analysis algorithms. The measured cyclic loads and displacements are used to determine the creep-fatigue displacements, the sample stiffness (or modulus) and the hysteresis damage energy as functions of the number of applied cycles associated with the fatigue loading. The hysteresis damage energy to failure was about 25 times greater in the SRC-PMMA samples (2000 J at 10(6) cycles) compared with bone cement or PMMA at the same number of cycles to failure (80 J) indicating much greater fatigue damage tolerance in these materials. This material, SRC-PMMA, may be applicable for use in several medical and/or dental applications. PMID- 8519926 TI - Adsorption of fibronectin and vitronectin onto Primaria and tissue culture polystyrene and relationship to the mechanism of initial attachment of human vein endothelial cells and BHK-21 fibroblasts. AB - The two cell culture substrata, tissue culture polystyrene (TCPS) and Primaria, were compared in order to determine whether a nitrogen-containing surface such as Primaria attracts cells by a different mechanism to an oxygen-containing surface (TCPS). The amounts of vitronectin (Vn) and fibronectin (Fn) which adsorb from the fetal bovine serum (FBS) component of the culture medium onto Primaria and TCPS were determined. Primaria adsorbed two- to threefold more Fn than TCPS, but adsorbed similar amounts of Vn from medium containing FBS. The Fn and Vn binding sites on Primaria were distinct, as adsorption was non-competitive between these two proteins. The amounts of Fn and Vn that adsorbed onto the two surfaces were compared to the concentration dependence of the cell attachment activities of Fn and Vn. Whereas the amounts of Fn which adsorbed onto TCPS were suboptimal for cell attachment, Primaria adsorbed an Fn surface density that was supraoptimal for attachment of human vein endothelial cells and BHK-21 fibroblasts. We conclude that Primaria differs from TCPS in that both Fn and Vn mediate initial cell attachment to Primaria when the culture medium contains FBS, whereas cell attachment to TCPS is dependent upon Vn. PMID- 8519927 TI - Excretion of a radiolabelled anticancer biodegradable polymeric implant from the rabbit brain. AB - The elimination of a clinically used anticancer biodegradable polymer implant (Gliadel) in the rabbit brain was studied. The implant is composed of N,N-bis(2 chloroethyl)-N-nitrosourea (BCNU) (1.6 wt%) dispersed in a copolyanhydride matrix of 1,3-bis(p-carboxyphenoxypropane) (CPP) and sebacic acid (SA) in a 20:80 molar ratio. Four groups of rabbits were implanted with wafers loaded with BCNU, one in a 14C-SA-labelled polymer, another in a 14C-CPP-labelled polymer and two groups with 14C-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the 14C-SA-labelled polymer, approximately 10% of the radioactivity was found in the urine and 2% in the faeces, and about 10% remained in the device 7 d after implantation. In contrast, only 4% of the radioactivity of the 14C-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9 d, and at 21 d, 64% of the implanted 14C-CPP was found in the urine and faeces, and 29% was still in the recovered wafers. Approximately 50% of the BCNU in the wafers was released in 3 d, and over 95% was released after 6 d in the rabbit brain. This study demonstrates that BCNU-loaded polyanhydride is biodegradable and is excreted from the body primarily through the renal system. The water-soluble components SA and BCNU were rapidly excreted, while the insoluble CPP was gradually eliminated after a lag time of 9 d. PMID- 8519928 TI - Influence of mucin type on polymer-mucin rheological interactions. AB - There are numerous in vitro methods with which to investigate the mucoadhesive properties of polymers. One recent method is based on the measurement of rheological interactions between polymer and mucin, which implies the use of mucins isolated from the mucous tissue. The extraction and purification of glycoprotein fraction, which is responsible for rheological interaction, can modify the native structure of mucin or spoil it with exogenous substances. Therefore the particulars of the mucin employed (origin, purification grade, the effect of further treatments such as freezing or freeze-drying) are likely to be critical for the interaction. The aim of this work was to compare some commercial mucins of differing origin and grade of purification for their rheological interaction with well-known mucoadhesive polymers (polyacrylic acid and sodium carboxymethylcellulose). For polyacrylic acid, which is sensitive to ions, we found rheological interaction to be strongly influenced by mucin type. The removal of ions, with dialysis, improved the interaction. For sodium carboxymethylcellulose, which is less sensitive to ions, rheological interaction proved to be less dependent on mucin type and improved upon glycoprotein solubilization. PMID- 8519930 TI - Collagen implants remain supple not allowing fibroblast ingrowth. AB - Dense, reconstituted collagen membranes, using an optimized cross-linking protocol, were implanted subcutaneously into rats. After implantation, only a mild inflammatory response in the surrounding tissues was observed. The morphology of the fibroblasts around the membranes was seen to go through characteristic stages of proliferation and synthesis. In the 7 week follow-up it was found that these membranes did not allow any fibroblast ingrowth into their substance and remained completely intact and supple without signs of calcification, whereas the non-cross-linked controls proved to be completely degraded. The cross-linked reconstituted collagen may thus be considered for use in situations where neither incorporation nor dissolution of the biomaterial is desired. PMID- 8519929 TI - Relationship between reduction of complement activation by polysaccharide surfaces bearing diethylaminoethyl groups and their degree of substitution. AB - The relationships between substitution of hydroxyl (OH) by diethylaminoethyl (DEAE) groups on cellulose membranes and the resulting reduction of complement activation are not clear. As a model, Sephadex has been randomly substituted with DEAE groups. Modification of 10% of the glucose units, i.e. about 3% of the groups, had no noticeable effect on the complement activating capacity of the polymer surface, whereas 20% substitution dramatically reduced it. This result could be explained in part by the fact that Sephadex-specific antibodies are not adsorbed by this modified surface. Thus, they cannot enhance complement activation as they do on Sephadex or cellulose. Comparison of our results with those published on Hemophan led us to the conclusion that a similar effect could occur. However, the degree of substitution of the membrane surface is probably greater than that of the membrane core due to the preparation process. Comparison with Sephadex substituted with other groups, or with other polymers bearing a variable density of OH groups, led us to the conclusion that, as hypothesized by Chenoweth (Artif Organs 1984; 8: 281-287), reduction of the availability of OH groups decreases complement activation, but the relationship is probably not linear. Moreover, replacement by other groups results in additional modulations due to (i) interactions between the groups and proteins responsible for formation or decay of the amplifying C3 convertase and/or (ii) decrease in recognition of the modified surface by antibodies which enhance complement activation on polysaccharides. PMID- 8519931 TI - Water absorption characteristics of modified hydroxyapatite bone cements. AB - Water absorption characteristics of a range of modified hydroxyapatite (HA) reinforced poly(ethyl methacrylate)-n-butyl methacrylate (PEMA-nBMA) bone cements have been established. From gravimetric measurements, the kinetics of successive absorption and desorption cycles, equilibrium uptake, diffusion coefficients and solubility data have been determined. In general, the water uptake could be modelled by the classical laws of diffusion. The introduction of the HA reduced the water uptake of the bone cement, with a further decrease if the HA filler was surface treated with a silane coupling agent. However, the system comprising the silicated silanated HA-filled cement produced a large uptake of water, with relatively low diffusion coefficients, which is attributed to the presence of soluble sites in the matrix. PMID- 8519932 TI - Transmission electron microscopy observations at the interface of bone and four types of calcium phosphate ceramics with different calcium/phosphorus molar ratios. AB - Four kinds of calcium phosphate ceramics, beta-calcium pyrophosphate (Ca2P2O7), beta-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium/phosphorus molar ratios were 1, 1.5, 1.66 and 2, respectively. Particles (150-300 microns) of these ceramics were packed into holes (diameter 2.5 mm) made in the tibial metaphysis of mature male rats. At 2 weeks, 4 weeks, 8 weeks and 6 months after the operation, undecalcified specimens were prepared. Transmission electron microscopy showed that the bone-bonding behaviour of calcium phosphate ceramics at the interface with bone did not vary with the calcium/phosphate molar ratio. Amorphous substances or needle-like microcrystals were observed on the surface of the ceramics at 2 weeks after implantation. The ceramics showed direct continuity with small crystallites of bone tissue at 4 weeks, 8 weeks and 6 months after implantation. The ceramics appeared to be getting smaller with time. Collagen fibres were not observed at the bone/ceramic interface. Neither chemical bonding nor mechanical bonding by interlocking between bone and ceramics was described by morphological observation using transmission electron microscopy. PMID- 8519933 TI - Negative Poisson ratios and strain-dependent mechanical properties in arterial prostheses. AB - The elastic properties of two artificial arterial prostheses have been measured. One is a fibrillar polyurethane (PU) material, the other is an expanded polytetrafluoroethylene (ex-PTFE). It is shown that the conventional assumption of incompressibility is invalid for both materials and that changes in the thickness of the prosthetic artery wall must be measured directly. The ex-PTFE shows highly strain-dependent properties, the most significant being that of large negative through-thickness Poisson ratios, up to -11. These results have important consequences for matching the properties of prostheses to natural materials. PMID- 8519934 TI - [Reactive arthritis]. PMID- 8519935 TI - [Reactive arthritis caused by Yersinia enterocolitica and Chlamydia trachomatis]. AB - We studied the clinical course, microbiological investigations and laboratory parameters in 10 patients with reactive arthritis (ReA). The number of patients with arthritis included was 10. Triggering agents were: seven patients had positive agglutinating antibody against Yersinia enterocolitica. Three cases had positive antibody test against Chlamydia trachomatis. In all patients antibody test were recovered. The clinical finding were: 4 patients with polyarthritis, 4 mono-oligoarthritis and two cases sacroileitis. The mean of index active joints were 6 (1-14). More frequent pattern were episodes of arthritis with lower limbs joints involvement. Outcome were of 12.1 (2-24) months. All of culture were negative. The laboratory parameters were unremarkable, except ESR were higher, HLA B-27 were positive in 70% of patients. The radiological signs and synovial biopsy studies were not conclusive. Eight patients were treated with antibiotics, not did antibiotics affect over duration of ReA. PMID- 8519936 TI - [Descriptive study of 39 cases of hepatic abscess of pyogenic and amebic origin]. AB - Thirty nine cases of liver abscess--33 pyogenic (LAP) and 6 amebic (LAA)- attended in our hospital between 1980 and 1994, were reviewed. Mean patient age was 55.66 years (LAP) and 35.83 years (LAA), while the relation male/female was 2.3:1 and 5:1 respectively. The most usual underlying pathology in LAP was bile duct disease (39.39%). Four patients with LAA had travelled to endemic areas. Fever was the most frequent clinical finding (71.79%). Echography and/or CT scan confirmed the diagnosis in 32 patients (82.05%), with a sensitivity of 86.66 and 95.65% respectively. Positive cultures were found in 74.35% (39.13% polymicrobials), being E. Coli and K. Pneumoniae the most frequently isolated bacteria. In LAP pus cultures were positive in 73% and blood cultures in 55%. Diagnosis of LAA was made by wet mount smears/serology (3/3). Percutaneous drainage was performed in 41.02%, surgical drainage in 48.71 and 15.38% (all with LAP) received antibiotics exclusively. Four patients died (3 with LAP and 1 with LAA). PMID- 8519937 TI - [Clinico-radiologic characteristics of 8 cases of brain tuberculoma]. AB - Several problems are presented in differential diagnosis between cerebral tuberculomas and other brain lesions. Eight cases of cerebral tuberculomas diagnosed in our hospital between 1962 and 1992 were studied. Data about age, sex, HIV antibodies, clinical manifestation, tomographic images, non cerebral locations, diagnostic method, evolution and treatment resolution were collected. Eight cases were diagnosed, seven men and one woman, age 40.75 +/- 10 HIV antibodies in three patients were positive. Meningitis (4 cases) and weight loss (4 cases) were the first clinical features. Confusional state, fever and seizures were presented in three cases one (37.5%), ataxia in two cases (25%) and headache in one (12.5%). Lesions were sole in 62.5% of cases, and several in 37.5%. Were high density in 25.9% and low density in 75%. All patients presented a other localization of tuberculosis. Mycobacterium tuberculosis was isolated in sputum in 75% of cases. After six month, most of the lesions improved. PMID- 8519938 TI - [Immobility syndrome in patients being care for in a home care unit]. AB - OBJECTIVES: to asses in a group of elderly patients included in a Home Care Unit, the level of immobility, the functional status based on the Katz's index and the Red Cross scale, and their medical, psychological and social consequences. METHODS: assessment of elderly patients visited during three consecutive months, through and standardized protocol with 14 items related with the previous aspects. RESULTS: 114 elderly patients (71% females) were visited during this time. The mean age was 82.4 years. 71 patients (65.7%) had immobility, with a mean age of 83.4 years and females predominance. Based on the level of immobility, 24 patients were in bed and 44 patients were able to be in bed armchair. 74% of the patients were severely disabled on the activities daily living (Katz G); 85% of the patients had a severe physical disability (Red Cross scale 4-5), whereas a lower percentage (36%) had severe mental disability (Red Cross scale 4-5). Neurological disorders were the most frequent etiology of immobility (72%), with only one cause in 27 patients, two causes in 20 patients and more than three causes in 24 patients. Medical consequences were the most frequent, mainly urinary and chest infections, pressure sores and constipation. CONCLUSIONS: Immobility's syndrome represents a common medical problem in the geriatric care, related specially with the neurological and osteo-articular disorders, conditioning a high mobility. PMID- 8519939 TI - [Acute ischemia of the lower limb in a patient with temporal arteritis and rheumatoid arthritis, carrier of anticardiolipin antibodies]. AB - We report a case of Temporal Arteritis, carrier of IgG anticardiolipin antibodies, who presented seronegative polyarthritis with AR criteria after 7 months. Three months later he developed acute ischemia in the right leg, which induced to amputate it. The biopsy showed thrombosis of the femoral arteria, and a dense lymphoplasmocytic infiltrate in its wall. We underline this association (TA-RA) with anticardiolipin antibodies, the exceptional affectation of the femoral arteries in this disease and the probable participation of anticardiolipin antibodies in the genesis of the arterial thrombosis. PMID- 8519940 TI - [Acute eosinophilic pneumonia: presentation of a case and review of the literature]. AB - Pulmonary eosinophilias are characterized by the appearance of lung infiltrates by eosinophils and the presence, commonly, of peripheral blood eosinophilia. Among idiopathic pulmonary eosinophilias, with no evidence of any cause or underlying disease, chronic eosinophilic pneumonia is the most characteristic. Recently, there has been described a few cases of eosinophilic pneumonia with many similarities to chronic eosinophilic pneumonia but with a shorter clinical course, a very good response to corticoid therapy, and without tendency to relapse. This process has been named acute eosinophilic pneumonia. We present a case of this entity and review the literature, emphasizing on the potential severity of this disease, which often conduce to progressive respiratory failure, and its excellent prognosis after appropriate treatment. PMID- 8519941 TI - [Recurrent bronchiolitis obliterans organizing pneumonia as first manifestation of polymyositis]. AB - The case of an idiopathic polymyositis preceded by several episodes compatible with the diagnosis of bronchiolitis obliterans organizing pneumonia is herein reported. This kind of pulmonary affection in polymyositis can be simultaneous or later to the diagnosis of the systemic disease, but as the first manifestation is exceptional. In the case we report, paradoxically, when the diagnosis of polymyositis was made the patient had not clinical or radiographic bronchopulmonary affection. If the first clinical manifestation of an autoimmune disease like polymyositis can be an idiopathic bronchiolitis obliterans organizing pneumonia, we think that a prolonged follow up of these patients is necessary. PMID- 8519942 TI - [Acyclovir nephrotoxicity]. AB - We are presenting the case of a seventy-six year old male infected with Herpes zoster of the trigeminal nerve. He had no previous nephropathology, but developed acute renal failure following the administration of an intravenous bolus of Acyclovir. The existing literature was reviewed. Possible pathogenic mechanisms are discussed, and precautions against nephrotoxicity are emphasized. PMID- 8519943 TI - [Cardiac tamponade in a woman with primary hypothyroidism]. AB - Pericardial effusion is not infrequent as a manifestation of hypothyroidism, however, cardiac tamponade is exceptional in these patients. We report a case of a female patient with cardiac tamponade that in the forward workshop was diagnosed of primary hypothyroidism. A brief presentation of clinical history is reported. The literature's review emphasizes the rarity of this case, the importance of the knowledge of triggering factors to establish a precious diagnosis and satisfactory clinical evolution with hormonal treatment without recurrences of the cardiac tamponade after pericardiocentesis is performed, although the resolution of the pericardial effusion is usually slow. PMID- 8519944 TI - [Leiomyoma-dependent ileal invagination as a cause of intermittent intestinal obstruction]. AB - We report the case of a 35-years-old-woman with history of abdominal surgery who presented several episodes of intermittent intestinal obstruction. Postoperative adhesions were suspected; laparoscopy surgery was made and uterine and anexial inflammation was observed. She was discharge with the diagnosis of inflammatory pelvic disease. Posteriorly, she was admitted with a new episode of intestinal obstruction. At laparotomy, intestinal intussusception was founded due to the presence of intestinal leiomyoma. We stress the relevance of two possible etiologies of intestinal obstruction; the coexistence of them difficult the diagnosis. Epidemiology, clinical presentation and diagnosis of leiomyomas of small intestine were reviewed. PMID- 8519945 TI - [Neurologic manifestations of Whipple disease]. AB - Pure neurologic Whipple's disease (WD) may be suspected by same clinical data (dementia-ophthalmoplegia-myoclonus triad, oculomasticatory myorhythmia) with support of MRI. Diagnosis is confirmed by intestinal and/or brain biopsy. Early recognition is critical in a disease that can lead to irreversible neurologic sequelae and that can potentially be cured. Despite therapy, relapses in patients with WD are common, being neurologic recurrence the most frequent and serious. Antibiotics that do not cross the blood-brain barrier are not adequate initial therapy for WD, because they predispose to neurologic relapse. Patients with WD should be treated for one year with antibiotics that cross the blood-brain barrier (such as parenteral penicillin+streptomycin, followed by oral trimethoprim-sulfamethoxazole). CNS relapse is usually resistant to therapy. PMID- 8519946 TI - [Colitis induced by non-steroidal anti-inflammatory agents]. PMID- 8519947 TI - [Effectiveness of calcium antagonists in the treatment of psoriasis]. PMID- 8519948 TI - [Sterno-clavicular arthritis in patients without known risk factors]. PMID- 8519949 TI - [Treatment of pulmonary thromboembolism with low molecular weight heparin]. PMID- 8519950 TI - [Pseudothrombocytopenia of 5 years of development]. PMID- 8519951 TI - [Retrospective study of the epidemiologic characteristics of HIV infection in a regional hospital]. PMID- 8519952 TI - [Porphyria cutanea tarda, hepatocarcinoma and hepatitis C virus infection]. PMID- 8519953 TI - [Hemolytic crisis in a glucose-6-phosphate dehydrogenase deficient patient after the ingestion of a dry fruit mixture]. PMID- 8519954 TI - [Pulmonary infection caused by Pasteurella multocida]. PMID- 8519955 TI - Compliance of thin filaments in skinned fibers of rabbit skeletal muscle. AB - The mechanical compliance (reciprocal of stiffness) of thin filaments was estimated from the relative compliance of single, skinned muscle fibers in rigor at sarcomere lengths between 1.8 and 2.4 micron. The compliance of the fibers was calculated as the ratio of sarcomere length change to tension change during imposition of repetitive cycles of small stretches and releases. Fiber compliance decreased as the sarcomere length was decreased below 2.4 micron. The compliance of the thin filaments could be estimated from this decrement because in this range of lengths overlap between the thick and thin filaments is complete and all of the myosin heads bind to the thin filament in rigor. Thus, the compliance of the overlap region of the sarcomere is constant as length is changed and the decrease in fiber compliance is due to decrease of the nonoverlap length of the thin filaments (the I band). The compliance value obtained for the thin filaments implies that at 2.4-microns sarcomere length, the thin filaments contribute approximately 55% of the total sarcomere compliance. Considering that the sarcomeres are approximately 1.25-fold more compliant in active isometric contractions than in rigor, the thin filaments contribute approximately 44% to sarcomere compliance during isometric contraction. PMID- 8519956 TI - Force generation and work production by covalently cross-linked actin-myosin cross-bridges in rabbit muscle fibers. AB - To separate a fraction of the myosin cross-bridges that are attached to the thin filaments and that participate in the mechanical responses, muscle fibers were cross-linked with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and then immersed in high-salt relaxing solution (HSRS) of 0.6 M ionic strength for detaching the unlinked myosin heads. The mechanical properties and force-generating ability of the cross-linked cross-bridges were tested with step length changes (L-steps) and temperature jumps (T-jumps) from 6-10 degrees C to 30-40 degrees C. After partial cross-linking, when instantaneous stiffness in HSRS was 25-40% of that in rigor, the mechanical behavior of the fibers was similar to that during active contraction. The kinetics of the T-jump-induced tension transients as well as the rate of the fast phase of tension recovery after length steps were close to those in unlinked fibers during activation. Under feedback force control, the T-jump initiated fiber shortening by up to 4 nm/half-sarcomere. Work produced by a cross linked myosin head after the T-jump was up to 30 x 10(-21) J. When the extent of cross-linking was increased and fiber stiffness in HSRS approached that in rigor, the fibers lost their viscoelastic properties and ability to generate force with a rise in temperature. PMID- 8519957 TI - Evidence for increased low force cross-bridge population in shortening skinned skeletal muscle fibers: implications for actomyosin kinetics. AB - The dynamic characteristics of the low force myosin cross-bridges were determined in fully calcium-activated skinned rabbit psoas muscle fibers shortening under constant loads (0.04-0.7 x full isometric tension Po). The shortening was interrupted at various times by a ramp stretch (duration, 10 ms; amplitude, up to 1.8% fiber length) and the resulting tension response was recorded. Except for the earlier period of velocity transients, the tension response showed nonlinear dependence on stretch amplitude; i.e., the magnitude of the tension response started to rise disproportionately as the stretch exceeded a critical amplitude, as in the presence of inorganic phosphate (Pi). This result, as well as the result of stiffness measurement, suggests that the low force cross-bridges similar to those observed in the presence of Pi (presumably A.M.ADP.Pi) are significantly populated during shortening. The critical amplitude of the shortening fibers was greater than that of isometrically contracting fibers, suggesting that the low force cross-bridges are more negatively strained during shortening. As the load was reduced from 0.3 to 0.04 P0, the shortening velocity increased more than twofold, but the amount of the negative strain stayed remarkably constant (approximately 3 nm). This This insensitiveness of the negative strain to velocity is best explained if the dissociation of the low force cross-bridges is accelerated approximately in proportion to velocity. Along with previous reports, the results suggest that the actomyosin ATPase cycle in muscle fibers has at least two key reaction steps in which rate constants are sensitively regulated by shortening velocity and that one of them is the dissociation of the low force A.M.ADP.Pi cross-bridges. This step may virtually limit the rate of actomyosin ATPase turnover and help increase efficiency in fibers shortening at high velocities. PMID- 8519958 TI - Analysis of the structure of dimeric DNA catenanes by electron microscopy. AB - We analyzed the structure of open-circular and supercoiled dimeric DNA catenanes generated by site-specific recombination in vitro. Electron microscopy of open circular catenanes shows that the number of duplex crossings in a plane is a linear function of the number of catenane interlinks (Ca/2), and that the length of the catenane axis is constant, independent of Ca. These relationships are similar to those observed with supercoiled DNA. Statistical analyses reveal, however, that the conformations of the individual rings of the catenanes are similar to those of unlinked circles. The distribution of distances between randomly chosen points on separate rings depends strongly on Ca and is consistent with a sharp decrease in the center-of-mass separation between rings with increasing Ca. Singly linked supercoiled catenanes are seen by microscopy to be linked predominantly through terminal loops in the respective superhelices. The observations suggest that chain entropy is a major factor determining the conformation of DNA catenanes. PMID- 8519960 TI - Geometry and energetics of DNA basepairs and triplets from first principles quantum molecular relaxations. AB - A first principles model for calculating hydrogen bonding interactions, previously applied to water, is here applied to the more difficult problem of interactions between DNA bases. We first consider the energetics and geometry for the A-T and the G-C basepairs, comparing our results to other calculated results as well as to experiment. Next, we study the interactions of isomorphic DNA base triplet structures, which are important because of their suggested role in the recombination process. We find that energetically the third base in the triplet tends to favor a position along the dyadic axis, where it is hydrogen bonded to both bases in the duplex. PMID- 8519959 TI - Chain folding and A:T pairing in human telomeric DNA: a model-building and molecular dynamics study. AB - The various types of chain folding and possible intraloop as well as interloop base pairing in human telomeric DNA containing d(TTAG3) repeats have been investigated by model-building, molecular mechanics, and molecular dynamics techniques. Model-building and molecular mechanics studies indicate that it is possible to build a variety of energetically favorable folded-back structures with the two TTA loops on same side and the 5' end thymines in the two loops forming TATA tetrads involving a number of different intraloop as well as interloop A:T pairing schemes. In these folded-back structures, although both intraloop and interloop Watson-Crick pairing is feasible, no structure is possible with interloop Hoogsteen pairing. MD studies of representative structures indicate that the guanine-tetraplex stem is very rigid and, while the loop regions are relatively much more flexible, most of the hydrogen bonds remain intact throughout the 350-ps in vacuo simulation. The various possible TTA loop structures, although they are energetically similar, have characteristic inter proton distances, which could give rise to unique cross-peaks in two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments. These folded-back structures with A:T pairings in the loop region help in rationalizing the data from chemical probing and other biochemical studies on human telomeric DNA. PMID- 8519961 TI - Fourier transform infrared spectroscopy indicates a major conformational rearrangement in the activation of rhodopsin. AB - The study of the structural differences between rhodopsin and its active form (metarhodopsin II) has been carried out by means of deconvolution analysis of infrared spectra. Deconvolution techniques allow the direct identification of the spectral changes that have occurred, which results in a significantly different view of the conformational changes occurring after activation of the receptor as compared with previous difference spectroscopy analysis. Thus, a number of changes in the bands assigned to solvent-exposed domains of the receptor are detected, indicating significant decreases in extended (beta) sequences and in reverse turns, and increases in irregular/aperiodic sequences and in helices with a non-alpha geometry, whereas there is no decrease in alpha-helices. In addition to secondary structure conversions, qualitative alterations within a given secondary structure type are detected. These are seen to occur in both reverse turns and helices. The nature of this spectral change is of great importance, since a clear alteration in the helices bundle core is detected. All these changes indicate that the rhodopsin --> metarhodopsin II transition involves not a minor but a major conformational rearrangement, reconciling the infrared data with the energetics of the activation process. PMID- 8519962 TI - Direct observation of sub-picosecond equilibration of excitation energy in the light-harvesting antenna of Rhodospirillum rubrum. AB - Excitation energy transfer in the light-harvesting antenna of Rhodospirillum rubrum was studied at room temperature using sub-picosecond transient absorption measurements. Upon excitation of Rs. rubrum membranes with a 200 fs, 600 nm laser flash in the Qx transition of the bacteriochlorophyll-a (BChl-a) absorption, the induced transient absorption changes in the Qy region were monitored. In Rs. rubrum membranes the observed delta OD spectrum exhibits ground state bleaching, excited state absorption and stimulated emission. Fast Qx --> Qy relaxation occurs in approximately 100-200 fs as reflected by the building up of stimulated emission. An important observation is that the zero-crossing of the transient difference absorption (delta OD) spectrum exhibits a dynamic redshift from 863 to 875 nm that can be described with by a single exponential with 325 fs time constant. The shape of the transient difference spectrum observed in a purified subunit of the core light-harvesting antenna, B820, consisting of only a single interacting pair of BChl-as, is similar to the spectrum observed in Rs. rubrum membranes and clearly different from the spectrum of BChl-a in a protein/detergent mixture. In the B820 and monomeric BChl-a preparations the 100 200 fs Qx --> Qy relaxation is still observed, but the dynamic redshift of the delta OD spectrum is absent. The spectral kinetics observed in the Rs. rubrum membranes are interpreted in terms of the dynamics of excitation equilibration among the antenna subunits that constitute the inhomogeneously broadened antenna. A simulation of this process using a set of reasonable physical parameters is consistent with an average hopping time in the core light harvesting of 220-270 fs, resulting in an average single-site excitation lifetime of 50-70 fs. The observed rate of this equilibration process is in reasonable agreement with earlier estimations for the hopping time from more indirect measurements. The implications of the findings for the process of excitation trapping by reaction centers will be discussed. PMID- 8519964 TI - Combined effects of light and water stress on chloroplast volume regulation. AB - A nuclear magnetic resonance technique was used to measure changes in the water content of Acer platanoides chloroplasts in leaf discs that had reached osmotic equilibrium with external solutions either in the dark or under exposure to light. Results showed that chloroplast volume regulation (CVR) maintained constant water content in the chloroplasts over a range of water potentials in the dark, but CVR failed when the water potential fell below a critical value. The critical potential was lower in the dark in sun leaves than in shade leaves. Upon exposure to intense light, CVR remained effective in sun leaves over the same range as in the dark, but it failed in shade leaves at all water potentials. Osmolytes are necessary for CVR, but KCl is relatively ineffective; increased concentrations of intracellular KCl did not fully support an increase in the range of CVR. The results indicate that leaves need reserve supplies of cytosolic osmolytes to maintain CVR at low water potentials, and a larger reserve supply is needed in leaves that are exposed to intense light. PMID- 8519963 TI - Femtosecond probe of structural analogies between chlorosomes and bacteriochlorophyll c aggregates. AB - Bacteriochlorophyll c pigments extracted from light harvesting chlorosomes in green photosynthetic bacteria are known to self-assemble into aggregates whose electronic spectroscopy resembles that of intact chlorosomes. Femtosecond optical experiments reveal that the chlorosomes and their reconstituted aggregates exhibit closely analogous internal energy transfer kinetics and exciton state evolution. These comparisons furnish compelling new evidence that proteins do not exert a major local role in the BChl c antenna pigment organization of intact chlorosomes. PMID- 8519965 TI - Nuclear magnetic resonance study of spin relaxation and magnetic field gradients in maple leaves. AB - 1H Nuclear magnetic resonance techniques were used to measure the distributions of spin-spin relaxation times, T2, and of magnetic field gradients in both the chloroplast and nonchloroplast water compartments of maple leaves (Acer platanoides). Results showed that encounters between water molecules and membranes inside chloroplasts provide an inefficient relaxation mechanism; i.e., chloroplast membranes interact weakly with water molecules. Gradient measurements indirectly measured the sizes of chloroplasts by showing that water in the chloroplasts is confined to small compartments a few microns in diameter. A comparison between measured gradients and gradients calculated for a model leaf indicated that chloroplasts are somewhat more likely to occupy positions along cell walls adjacent to air spaces, but also they may be found in the interiors of cells. PMID- 8519966 TI - Nonlinear annihilation of excitations in photosynthetic systems. AB - The theory of the singlet-singlet annihilation in quasi-homogeneous photosynthetic antenna systems is developed further. In the new model, the following important contributions are taken into account: 1) the finite excitation pulse duration, 2) the occupation of higher excited states during the annihilation, 3) excitation correlation effects, and 4) the effect of local heating. The main emphasis is concentrated on the analysis of pump-probe kinetic measurements demonstrating the first two above possible contributions. The difference with the results obtained from low-intensity fluorescence kinetic measurements is highlighted. The experimental data with picosecond time resolution obtained for the photosynthetic bacterium Rhodospirillum rubrum at room temperature are discussed on the basis of this theory. PMID- 8519967 TI - New tubular single-stranded helix of poly-L-amino acids suggested by molecular mechanics calculations: I. Homopolypeptides in isolated environments. AB - A search was made in terms of molecular mechanics calculation for tubular, or pore-forming, single-stranded helices of poly-L-amino acids. Such a helix was found in the vicinity of (phi, psi, omega) = 81 degrees, 98 degrees, 170 degrees) in the conformational space. It was the 6.2(20) helix of right-handedness. The 6.2(20) helix, here named the "mu helix," had a cylindrical pore along its helical axis. The diameter of the pore was 6.6 A on the basis of the atom centers of carbonyl carbons and amino nitrogens. The left-handed mu helix was less stable than the right-handed counterpart. The conformation energy of the mu helix, expressed relative to that of the alpha helix of the same polypeptide, depended to a great extent on amino acid composition. It varied over a range of a few kilocalories per mol per residue above and below the conformation energy of the alpha helix of the same polypeptide. This marked diversity in the relative conformation energy of the mu helix can be ascribed primarily to the difference in the relative position of alpha-carbons between the mu and the alpha helices. The conformational entropy made only a small contribution, if any, to the relative stability of the mu helix. There was a hydrogen-bonded network of side chains in the mu helices of poly-L-glutamine and poly-L-asparagine. PMID- 8519968 TI - Quantitative analysis of molecular orientation in chlorophyll a Langmuir monolayer: a polarized visible reflection spectroscopic study. AB - Polarized visible reflection spectra of a chlorophyll a (Chl.a) Langmuir monolayer have been measured in situ at various surface pressures. By applying Hansen's optics to the three-phase plane-bounded system (air/Chl.a monolayer/water), the negative reflection absorbances observed were reproduced satisfactorily by the theoretical calculation. Molecular orientation of Chl.a in the monolayer was evaluated quantitatively as a function of surface pressure, from the reflection absorbance of p- and s-polarized spectra of the red (Qy) band. It has been proven that Chl.a molecules in the monolayer form aggregates (islands) even in the low surface pressure region and that during the monolayer compression the molecules are gradually reorganized from inhomogeneous islands to ordered structures, with the chromophores oriented on the average vertically to the water surface. PMID- 8519969 TI - Analytical approach to the recovery of short fluorescence lifetimes from fluorescence decay curves. AB - Considerable effort in instrument development has made possible detection of picosecond fluorescence lifetimes by time-correlated single-photon counting. In particular, efforts have been made to narrow markedly the instrument response function (IRF). Less attention has been paid to analytical methods, especially to problem of discretization of the convolution integral, on which the detection and quantification of short lifetimes critically depends. We show that better discretization methods can yield acceptable results for short lifetimes even with an IRF several times wider than necessary for the standard discretization based on linear approximation (LA). A general approach to discretization, also suitable for nonexponential models, is developed. The zero-time shift is explicitly included. Using simulations, we compared LA, quadratic, and cubic approximations. The latter two proved much better for detection of short lifetimes and, in that respect, they do not differ except when the zero-time shift exceeds two channels, when one can benefit from using the cubic approximation. We showed that for LA in some cases narrowing the IRF beyond FWHM = 150 ps is actually counterproductive. This is not so for quadratic and cubic approximations, which we recommend for general use. PMID- 8519970 TI - Molecular mechanisms determining the strength of receptor-mediated intermembrane adhesion. AB - The strength of receptor-mediated cell adhesion is directly controlled by the mechanism of cohesive failure between the cell surface and underlying substrate. Unbinding can occur either at the locus of the specific bond or within the bilayer, which results in tearing the hydrophobic anchors from the membrane interior. In this work, the surface force apparatus has been used to investigate the relationship between the receptor-ligand bond affinities and the dominant mechanism of receptor-coupled membrane detachment. The receptors and ligands used in this study were membrane-bound streptavidin and biotin analogs, respectively, with solution affinities ranging over 10 orders of magnitude. With the optical technique of the surface force apparatus, the occurrence of membrane rupture was directly visualized in situ. The latter observations together with measurements of the corresponding intermembrane adhesive strengths were used to identify the dominant failure pathway for each streptavidin-analog pair. Even in cases where the membrane pull-out energy exceeded the equilibrium bond energy, cohesive failure occurred within the membrane interior at nearly all bond affinities considered. These results are consistent with previous findings and provide direct support for the commonly held view that, under nonequilibrium conditions of applied external stress, the gradient of the bond energy, not the equilibrium bond energy alone, determines the adhesive strength. Furthermore, our findings directly demonstrate that, in the presence of competing failure mechanisms, the preferred detachment mechanism- hence, the adhesive strength-will be determined by the bond that exhibits the weakest tensile strength. Because the tensile strength is determined by the gradient of the unbinding energy, the critical detachment force will be determined by both the bond energy and the effective bond length. PMID- 8519971 TI - Measuring diameters of rod-shaped bacteria in vivo with polarized light scattering. AB - The angular function for elements of the Mueller matrix for polarized light scattering from suspensions of microorganisms is known to be reproducible for different growths of a given bacterial strain in the log (or exponential) phase of growth. The reason for this, the stability of the size and shape distribution for cells, is briefly discussed. Experiments were performed using suspensions of two different strains of Escherichia coli cells in log phase and measuring the angular dependence of the Mueller matrix ratio S34/S11. Calculations were then performed using the coupled dipole approximation to model electromagnetic scattering from particles where the shape of an individual cell was approximated by a cylinder capped with hemispheres of the same radius as the cylinder. Using previously measured values for the length distribution and index of refraction of the cells, the calculated scattering curve was found to fit the measured curve very well. The values obtained for the cell diameters were quite close to diameters previously measured by optical microscopy. Thus this method provides a rapid and convenient method for monitoring bacterial diameters in vivo even when there is an appreciable distribution of bacterial lengths in the population. PMID- 8519972 TI - Calcium response of helper T lymphocytes to antigen-presenting cells in a single cell assay. AB - We developed a dynamic, single-cell assay involving alternating differential interference contrast and fluorescence microscopy, together with digital imaging, for both viewing the physical interaction of live helper T lymphocytes (Th cells) with antigen-presenting cells (APCs) and monitoring the increases in the intracellular free calcium concentration of the Th cell, an early event in Th cell activation. We obtained Th-APC conjugates by allowing the Th cells to migrate toward and interact with APCs that either settled nearby or had been micromanipulated in close proximity to the Th cells. Th cell motility played an important role in initiating Th-APC contacts but not in determining the Th cell calcium response. We found that the intracellular calcium responses of individual Th cells are heterogeneous and an all-or-none phenomenon, independent of antigen concentration. However, the fraction of Th-APC conjugates involving responding Th cells is an increasing function of the antigen concentration. Finally, we measured some characteristics of the developing Th-APC contact area. We used all of these data together with previously developed mathematical models to estimate that only 1 to 20 major histocompatibility class II-antigen complexes are required in the initial Th-APC contact area to elicit a Th cell calcium response. PMID- 8519973 TI - Preferential solvation and the selectivity of lipid-protein interactions. PMID- 8519974 TI - Toward understanding amyloid aggregation. PMID- 8519975 TI - Structural predictions of the binding site architecture for monoclonal antibody NC6.8 using computer-aided molecular modeling, ligand binding, and spectroscopy. AB - Monoclonal antibody NC6.8 binds the superpotent sweetener ligand N-(p cyanophenyl)-N'-(diphenylmethyl) guanidineacetic acid with high affinity (Kd = 53 nM). Using computer-aided molecular modeling and several experimental techniques, such as competitive ligand binding, absorbance spectroscopy, and fluorescence spectroscopy, we have predicted the structure of the variable domain fragment (Fv) and identified the key residues in the combining site of the antibody. We have identified nine specific amino acids as being involved in ligand recognition and complexation. Most notable are H:33W, which is responsible for ligand-induced tryptophan fluorescence quenching, H:56R, which forms a salt bridge with the carboxylate moiety of the ligand, and L:34H, which, deep in the binding site, interacts with the cyanophenyl portion of the ligand. Two residues located deep in the putative binding pocket, H:35E and H:50E, provide the negatively charged potential for interaction with the protonated aryl nitrogen and the positive guanidinium group. These modeling predictions were made before the solution of high-resolution structures of the native Fab (2.6 A) and the Fab-ligand complex (2.2 A). Comparisons between the theoretical model and experimental native and liganded Fab structures are made. PMID- 8519976 TI - Poly-3-hydroxybutyrate/polyphosphate complexes form voltage-activated Ca2+ channels in the plasma membranes of Escherichia coli. AB - The lipidic polymer, poly-3-hydroxybutyrate (PHB), is found in the plasma membranes of Escherichia col complexed to calcium polyphosphate (CaPPi). The composition, location, and putative structure of the polymer salt complexes led Reusch and Sadoff (1988) to propose that the complexes function as Ca2+ channels. Here we use bilayer patch-clamp techniques to demonstrate that voltage-activated Ca2+ channels composed of PHB and CaPPi are in the plasma membranes of E. coli. Single channel calcium currents were observed in vesicles of plasma membranes incorporated into planar bilayers of synthetic 1-palmitoyl, 2-oleoyl phosphatidylcholine. The channels were extracted from cells and incorporated into bilayers, where they displayed many of the signal characteristics of protein Ca2+ channels: voltage-activated selective for divalent over monovalent cations, permeant to Ca2+, manner by La3+, Co2+, Cd2+, and Mg2+, in that order. The channel-active extract, purified by size exclusion chromatography, was found to contain only PHB and CaPPi. This composition was confirmed by the observation of comparable single channel currents with complexes reconstituted from synthetic CaPPi and PHB, isolated from E. coli. This is the first report of a biological non-proteinaceous calcium channel. We suggest that poly-3-hydroxybutyrate/calcium polyphosphate complexes are evolutionary antecedents of protein Ca2+ channels. PMID- 8519977 TI - The radius of gyration of native and reductively methylated myosin subfragment-1 from neutron scattering. AB - Reductive methylation of nearly all lysine groups of myosin subfragment-1 (S1) was required for crystallization and solution of its structure at atomic resolution. Possible effects of such methylation on the radius of gyration of chicken skeletal muscle myosin S1 have been investigated by using small-angle neutron scattering. In addition, we have investigated the effect of MgADP.Vi, which is thought to produce an analog of the S1.ADP.Pi state, on the S1 radius of gyration. We find that although methylation of S1, with or without SO42- ion addition, does not significantly alter the structure, addition of ADP plus vanadate does decrease the radius of gyration significantly. The S1 crystal structure predicts a radius of gyration close to that measured here by neutron scattering. These results suggest that the overall shape by crystallography resembles nucleotide-free S1 in solution. In order to estimate the effect of residues missing from the crystal structure, the structure of missing loops was estimated by secondary-structure prediction methods. Calculations using the complete crystal structure show that a simple closure of the nucleotide cleft by a rigid-body torsional rotation of residues (172-180 to 670) around an axis running along the base of the cleft alone does not produce changes as large as seen here and in x-ray scattering results. On the other hand, a rigid body rotation of either the light-chain binding domain (767 to 843 plus light chains) or of a portion of 20-kDa peptide plus this domain (706 to 843 plus light chains) is more readily capable of producing such changes. PMID- 8519978 TI - Dielectrophoretic forces and potentials induced on pairs of cells in an electric field. AB - A combined numerical/experimental study is reported of the membrane potentials and dielectrophoretically induced forces between cells, membrane pressures, and velocity of attraction of cells under the influence of an electric field. This study was designed to explore electrical and mechanical effects produced by a field on cells in close proximity or undergoing electrically induced fusion. Laplace's equation for pairs of membrane-covered spheres in close proximity was solved numerically by the boundary element method, and the electrically induced forces on the cells and between cells were obtained by evaluating the Maxwell stress tensor. The velocity of approach of erythrocyte ghosts or fused ghosts in a 60-Hz field of 6 V/mm was measured experimentally, and the data were interpreted by using Batchelor's theory for hydrodynamic interaction of hard spheres. The numerical results show clearly the origin of the dielectrophoretic pressures and forces in fused and unfused cells and the effects of a nearby cell on the induced membrane potentials. The experimental results agree well with predictions based on the simple electrical model of the cell. The analysis shows the strong effect of hydrodynamic interactions between the cells in determining their velocity of approach. PMID- 8519979 TI - Spontaneous electrical and calcium oscillations in unstimulated pituitary gonadotrophs. AB - Single pituitary cells often fire spontaneous action potentials (APs), which are believed to underlie spiking fluctuations in cytosolic calcium concentration ([Ca2+]i). To address how these basal [Ca2+]i fluctuations depend on changes in plasma membrane voltage (V), simultaneous measurements of V and [Ca2+]i were performed in rat pituitary gonadotrophs. The data show that each [Ca2+]i spike is produced by the Ca2+ entry during a single AP. Using these and previously obtained patch-clamp data, we develop a quantitative mathematical model of this plasma membrane oscillator and the accompanying spatiotemporal [Ca2+]i oscillations. The model demonstrates that AP-induced [Ca2+]i spiking is prominent only in a thin shell layer neighboring the cell surface. This localized [Ca2+]i spike transiently activates the Ca2(+)- dependent K+ current resulting in a sharp afterhyperpolarization following each voltage spike. In accord with experimental observations, the model shows that the frequency and amplitude of the voltage spikes are highly sensitive to current injection and to the blocking of the Ca(2+)-sensitive current. Computations also predict that leaving the membrane channels intact, the firing rate can be modified by changing the Ca2+ handling parameters: the Ca2+ diffusion rate, the Ca2+ buffering capacity, and the plasma membrane Ca2+ pump rate. Finally, the model suggests reasons that spontaneous APs were seen in some gonadotrophs but not in others. This model provides a basis for further exploring how plasma membrane electrical activity is involved in the control of cytosolic calcium level in unstimulated as well as agonist-stimulated gonadotrophs. PMID- 8519980 TI - Kinetics of microtubule catastrophe assessed by probabilistic analysis. AB - Microtubules are cytoskeletal filaments whose self-assembly occurs by abrupt switching between states of roughly constant growth and shrinkage, a process known as dynamic instability. Understanding the mechanism of dynamic instability offers potential for controlling microtubule-dependent cellular processes such as nerve growth and mitosis. The growth to shrinkage transitions (catastrophes) and the reverse transitions (rescues) that characterize microtubule dynamic instability have been assumed to be random events with first-order kinetics. By direct observation of individual microtubules in vitro and probabilistic analysis of their distribution of growth times, we found that while the slower growing and biologically inactive (minus) ends obeyed first-order catastrophe kinetics, the faster growing and biologically active (plus) ends did not. The non-first-order kinetics at plus ends imply that growing microtubule plus ends have an effective frequency of catastrophe that depends on how long the microtubules have been growing. This frequency is low initially but then rises asymptotically to a limiting value. Our results also suggest that an additional parameter, beyond the four parameters typically used to describe dynamic instability, is needed to account for the observed behavior and that changing this parameter can significantly affect the distribution of microtubule lengths at steady state. PMID- 8519981 TI - Finger-like lysing patterns of blood clots. AB - One-dimensional modeling of fibrinolysis (Senf, 1979; Zidansek and Blinc, 1991; Diamond and Anand, 1993) has accounted for the dissolution velocity, but the shape of the lysing patterns can be explained only by two- or three- drug-induced blood clot dissolution patterns obtained by proton nuclear magnetic resonance imaging, which can be described by the enzyme transport-limited system of fibrinolytic chemical equations with diffusion and perfusion terms (Zidansek and Blinc, 1991) in the reaction time approximation if the random character of gel porosity is taken into account. A two-dimensional calculation based on the Hele Shaw random walk models (Kadanoff, 1985; Liang, 1986) leads to fractal lysing patterns as, indeed, is observed. The fractal dimension of the experimental lysing patterns changes from 1.2 at the beginning of the experiments to a maximum of approximately 1.3 in the middle and then decreases toward one when the clot is recanalized. PMID- 8519982 TI - Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam: a molecular dynamics study. AB - Ordered water molecules are observed by crystallography and nuclear magnetic resonance to mediate protein-ligand interactions. Here, we examine the energetics of hydrating cavities formed at protein-ligand interfaces using molecular dynamics simulations. The free energies of hydrating two cavities in the active site of two liganded complexes of cytochrome P450cam were calculated by multiconfigurational thermodynamic integration. The complex of cytochrome P450cam with 2-phenyl-imidazole contains a crystallographically well defined water molecule mediating hydrogen bonds between the protein and the inhibitor. We calculate that this water molecule is stabilized by a binding free energy of 11.6 +/- kJ/mol. The complex of cytochrome P450cam with its natural substrate, camphor, contains a cavity that is empty in the crystal structure although a water molecule in it could make a hydrogen bond to camphor. Here, solvation of this cavity is calculated to be unfavorable by +15.8 +/- 5.0 kJ/mol. The molecular dynamics simulations can thus distinguish a hydrated interfacial cavity from an empty one. They also provide support for the notion that protein-ligand complexes can accommodate empty interfacial cavities and that such cavities are likely to be unhydrated unless more than one hydrogen bond can be made to a water molecule in the cavity. PMID- 8519983 TI - Effects of cellular pharmacology on drug distribution in tissues. AB - The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies. PMID- 8519984 TI - Estimating friction coefficients of mixed globular/chain molecules, such as protein/DNA complexes. AB - Existing methods for predicting translational friction properties of complex molecules start by explicitly building up their three-dimensional shape with spherical subunits. This treatment has been used especially for two types of systems: rigid assemblies and flexible chain molecules. However, many protein/DNA complexes such as chromatin consist of a small number of globular, relatively rigid, bound protein interspersed by long stretches of flexible DNA chain. I present a higher level of treatment of such macromolecules that avoids explicit subunit modeling as much as possible. An existing analytical formulation of the hydrodynamics equations is shown to be accurate when used with the present treatment. Thus the approach is fast and can be applied to hydrodynamic studies of highly degenerate multiple equilibria, such as those encountered in problems of the regulation of chromatin structure. I demonstrate the approach by predicting the effect of a hypothetical unwinding process in dinucleosomes and by simulating the distribution of sedimentation coefficients for cooperative and random models for a chromatin saturation process. PMID- 8519985 TI - Activation kinetics of recombinant mouse nicotinic acetylcholine receptors: mutations of alpha-subunit tyrosine 190 affect both binding and gating. AB - Affinity labeling and mutagenesis studies have demonstrated that the conserved tyrosine Y190 of the acetylcholine receptor (AChR) alpha-subunit is a key determinant of the agonist binding site. Here we describe the binding and gating kinetics of embryonic mouse AChRs with mutations at Y190. In Y190F the dissociation constant for ACh binding to closed channels was reduced approximately 35-fold at the first binding site and only approximately 2-fold at the second site. At both binding sites the association and dissociation rate constants were decreased by the mutation. Compared with wildtype AChRs, doubly liganded alpha Y190F receptors open 400 times more slowly but close only 2 times more rapidly. Considering the overall activation reaction (vacant-closed to fully occupied-open), there is an increase of approximately 6.4 kcal/mol caused by the Y-to-F mutation, of which at least 2.1 and 0.3 kcal/mol comes from altered agonist binding to the first and second binding sites, respectively. The closing rate constant of alpha Y190F receptors was the same with ACh, carbamoylcholine, or tetramethylammonium as the agonist. This rate constant was approximately 3 times faster in ACh-activated S, W, and T mutants. The equilibrium dissociation constant for channel block by ACh was approximately 2-fold lower in alpha Y190F receptors compared with in wildtype receptors, suggesting that there are changes in the pore region of the receptor as a consequence of the mutation. The activation reaction is discussed with regard to energy provided by agonist receptor binding contacts, and by the intrinsic folding energy of the receptor. PMID- 8519986 TI - Unilateral exposure of Shaker B potassium channels to hyperosmolar solutions. AB - This study tests the hypothesis that ion channels will be affected differently by external (extracellular) versus internal (cytoplasmic) exposure to hyperosmolar media. We looked first for effects on inactivation kinetics in wild-type Shaker B potassium channels. Although external hyperosmolar exposure did not alter the inactivation rate, internal exposure slowed both onset and recovery from fast inactivation. Differential effects on activation kinetics were then characterized by using a noninactivating Shaker B mutant. External hyperosmolar exposure slowed the late rising phase of macroscopic current without affecting the initial delay or early rising phase kinetics. By contrast, internal exposure slowed the initial steps in channel activation with only minimal changes in the later part of the rising phase. Neither external nor internal hyperosmolar exposure affected tail current rates in these noninactivating channels. Additionally, suppression of peak macroscopic current was approximately twofold smaller during external, as compared with internal, hyperosmolar exposure. Single-channel currents, observed under identical experimental conditions, showed a differential suppression equivalent to that seen in macroscopic currents. Apparently, during unilateral hyperosmolar exposure, changes in macroscopic peak current arise primarily from changes in single-channel conductance rather than from changes in equilibrium channel gating. We conclude that unilateral hyperosmolar exposure can provide information concerning the potential structural localization of functional components within ion-channel molecules. PMID- 8519987 TI - Voltage-dependent properties of three different gating modes in single cardiac Na+ channels. AB - Three different modes of Na+ channel action, the F mode (fast inactivating), the S mode (slowly inactivating), and the P mode (persistent), were studied at different potentials in exceptionally small cell-attached patches containing one and only one channel. Switching between the modes was independent of voltage. In the F mode, the mean open time (tau o) at -30 and -40 mV was 0.14 and 0.16 ms, respectively, which was significantly larger than at -60 and 0 mV, where the values were 0.07 and 0.08 ms, respectively. The time before which half of the first channel openings occurred (t 0.5), decreased from 0.58 ms at -60 mV to 0.14 ms at 0 mV. The fit of steady-state activation with a Boltzmann function yielded a half-maximum value (V 0.5) at -48.1 mV and a slope (k) of 5.6 mV. The mean open time in the S mode increased steadily from 0.12 ms at -80 mV to 1.09 ms at -30 mV, but was not prolonged further at -20 mV (1.07 ms). Concomitantly, t 0.5 decreased from 1.61 ms at -80 mV to 0.22 ms at -20mV. Here the midpoint of steady state activation was found at -61.2 mV, and the slope was 8.7 mV. The mean open time in the P mode increased from 0.07 ms at -60 mV to 0.45 ms at 0 mV and t 0.5 declined from 2.14 ms at -60 mV to 0.19 ms at +20 mV. Steady-state activation had its midpoint at -14.7 mV, and the slope was 10.9 mV. It is concluded that a single Na+ channel may switch among the F, S, and P mode and that the three modes differ by a characteristic pattern of voltage dependence of tau 0, t 0.5, and steady-state activation. PMID- 8519988 TI - Overexpression of the cystic fibrosis transmembrane conductance regulator in NIH 3T3 cells lowers membrane potential and intracellular pH and confers a multidrug resistance phenotype. AB - Because of the similarities between the cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance (MDR) proteins, recent observations of decreased plasma membrane electrical potential (delta psi) in cells overexpressing either MDR protein or the CFTR, and the effects of delta psi on passive diffusion of chemotherapeutic drugs, we have analyzed chemotherapeutic drug resistance for NIH 3T3 cells overexpressing different levels of functional CFTR. Three separate clones not previously exposed to chemotherapeutic drugs exhibit resistance to doxorubicin, vincristine, and colchicine that is similar to MDR transfectants not previously exposed to chemotherapeutic drugs. Two other clones expressing lower levels of CFTR are less resistant. As shown previously these clones exhibit decreased plasma membrane delta psi similar to MDR transfectants, but four of five exhibit mildly acidified intracellular pH in contrast to MDR transfectants, which are in general alkaline. Thus the MDR protein and CFTR-mediated MDR phenotypes are distinctly different. Selection of two separate CFTR clones on either doxorubicin or vincristine substantially increases the observed MDR and leads to increased CFTR (but not measurable MDR or MRP) mRNA expression. CFTR overexpressors also exhibit a decreased rate of 3H vinblastine uptake. These data reveal a new and previously unrecognized consequence of CFTR expression, and are consistent with the hypothesis that membrane depolarization is an important determinant of tumor cell MDR. PMID- 8519989 TI - C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism. AB - The lymphocyte voltage-gated K+ channel, Kv1.3, inactivates by a C-type process. We have elucidated the molecular basis for this process using a kinetic analysis of wild-type and mutant (A413V) Kv1.3 homo- and heteromultimeric currents in a mammalian lymphoid expression system. The medians of the measured inactivation time constants for wild-type and A413V homotetrameric currents are 204 and 4 ms, respectively. Co-expression of these subunits produces heteromultimeric channels manifesting inactivation kinetics intermediate between those of wild-type and A413V homomultimers. We have considered several models in which each subunit acts either independently or cooperatively to produce the observed inactivation kinetics. The cooperative model gives excellent fits to the data for any heteromultimeric composition of subunits, clearly distinguishing it from the independent models. In the cooperative model, the difference in free energy between the open and inactivated states of the channel is invariant with subunit composition and equals approximately 1.5 kcal/mol. Each subunit contributes equally to the activation free energy for transitions between open and inactivated states, with an A413V subunit decreasing the free energy barrier for inactivation (and for recovery from inactivation) by approximately 0.6 kcal/mol. Our results are consistent with a physical model in which the outer mouth of the channel constricts during C-type inactivation (G. Yellen, D. Sodickson, T. Chen, and M.E. Jurman, 1994, Biophys. J. 66:1068-1075). PMID- 8519990 TI - Induction of endogenous channels by high levels of heterologous membrane proteins in Xenopus oocytes. AB - Xenopus oocytes are widely employed for heterologous expression of cloned proteins, particularly electrogenic molecules such as ion channels and transporters. The high levels of expression readily obtained permit detailed investigations without interference from endogenous conductances. Injection of min K mRNA into Xenopus oocytes results in expression of voltage-dependent potassium-selective channels. Recent data show that injections of high concentrations of min K mRNA also induce a chloride current with very different biophysical, pharmacological, and regulatory properties from the min K potassium current. This led to the suggestion that the min K protein acts as an inducer of endogenous, normally silent oocyte ion channels. We now report that high levels of heterologous expression of many membrane proteins in Xenopus oocytes specifically induce this chloride current and a hyperpolarization-activated cation-selective current. The current is blocked by 4,4'-diisothiocyanostilbene-2 2'-disulphonic acid and tetraethylammonium, enhanced by clofilium, and is pH sensitive. Criteria are presented that distinguish this endogenous current from those due to heterologous expression of electrogenic proteins in Xenopus oocytes. Together with structure-function studies, these results support the hypothesis that the min K protein comprises a potassium-selective channel. PMID- 8519991 TI - Electrogenicity of the sodium transport pathway in the Na,K-ATPase probed by charge-pulse experiments. AB - A charge-pulse technique was designed to measure charge movements in the Na transport mode of the Na,K-ATPase in membrane fragments adsorbed to a planar lipid bilayer with high time resolution. 1) Na+ transport was measured as a function of membrane potential, and 2) voltage-dependent extracellular ion binding and release were analyzed as a function of Na+ concentration and membrane potential. The results could be fitted and explained on the basis of a Post Albers cycle by simulations with a mathematical model. The minimal reaction sequence explaining the electrogenicity of the pump consists of the following steps: (Na3)E1-P <--> P-E2(Na3) <--> P-E2(Na2) <--> P-E2(Na) <--> P-E2. The conformational change, E1 to E2, is electrogenic (beta 0 < or = 0.1) and the rate limiting step of forward Na+ transport with a rate constant of 25 s-1 (T = 20 degrees C). The first ion release step, P-E2(Na3) <--> P-E2(Na2), is the major charge translocating process (delta 0 = 0.65). It is probably accompanied by a protein relaxation in which the access structure between aqueous phase and binding site reduces the dielectric distance. The release of the subsequent Na+ ions has a significantly lower dielectric coefficient (delta1 = delta 2 = 0.2). Compared with other partial reactions, the ion release rates are fast (1400 s-1, 700 s-1, and 4000 s-1). On the basis of these findings, a refined electrostatic model of the transport cycle is proposed. PMID- 8519992 TI - The hemifusion intermediate and its conversion to complete fusion: regulation by membrane composition. AB - To fuse, membranes must bend. The energy of each lipid monolayer with respect to bending is minimized at the spontaneous curvature of the monolayer. Two lipids known to promote opposite spontaneous curvatures, lysophosphatidylcholine and arachidonic acid, were added to different sides of planar phospholipid membranes. Lysophosphatidylcholine added to the contacting monolayers of fusing membranes inhibited the hemifusion we observed between lipid vesicles and planar membranes. In contrast, fusion pore formation depended upon the distal monolayer of the planar membrane; lysophosphatidylcholine promoted and arachidonic acid inhibited. Thus, the intermediates of hemifusion and fusion pores in phospholipid membranes involve different membrane monolayers and may have opposite net curvatures, Biological fusion may proceed through similar intermediates. PMID- 8519993 TI - Influence of transbilayer area asymmetry on the morphology of large unilamellar vesicles. AB - The morphological consequences of differences in the monolayer surface areas of large unilamellar vesicles (LUVs) have been examined employing cryoelectron microscopy techniques. Surface area was varied by inducing net transbilayer transport of dioleoylphosphatidylglycerol (DOPG) in dioleoylphosphatidylcholine (DOPC):DOPG (9:1, mol:mol) LUVs in response to transmembrane pH gradients. It is shown that when DOPG is transported from the inner to the outer monolayer, initially invaginated LUVs are transformed to long narrow tubular structures, or spherical structures with one or more protrusions. Tubular structures are also seen in response to outward DOPG transport in DOPC:DOPG:Chol (6:1:3, mol:mol:mol) LUV systems, and when lyso-PC is allowed to partition into the exterior monolayer of DOPC:DOPG (9:1, mol:mol) LUVs in the absence of DOPG transport. Conversely, when the inner monolayer area is expanded by the transport of DOPG from the outer monolayer to the inner monolayer of non-invaginated LUVs, a reversion to invaginated structures is observed. The morphological changes are well described by an elastic bending theory of the bilayer. Identification of the difference in relaxed monolayer areas and of the volume-to-area ratio of the LUVs as the shape determining factors allows a quantitative classification of the observed morphologies. The morphology seen in LUVs supports the possibility that factors leading to differences in monolayer surface areas could play important roles in intracellular membrane transport processes. PMID- 8519994 TI - Phase separation dynamics and lateral organization of two-component lipid membranes. AB - The non-equilibrium dynamic ordering process of coexisting phases has been studied for two-component lipid bilayers composed of saturated di-acyl phospholipids with different acyl chain lengths, such as DC14PC-DC18PC and DC12PC DC18PC. By means of a microscopic interaction model and computer-simulation techniques the non-equilibrium properties of these two mixtures have been determined with particular attention paid to the effects of the non-equilibrium ordering process on membrane heterogeneity in terms of local and global lateral membrane organization. The results reveal that a sudden temperature change that takes the lipid mixture from the fluid one-phase region into the gel-fluid phase coexistence region leads to the formation of a large number of small lipid domains which slowly are growing in time. The growth of the lipid domains, which is limited by long-range diffusion of the lipid molecules within the two dimensional membrane plane, gives rise to the existence of a highly heterogeneous percolative-like structure with a network of interfacial regions that have properties different from those of the phase-separated gel and fluid bulk phases. The results, which are discussed in relation to recent experimental observations interpreted in terms of a percolative-like membrane structure within the two phase region (Almeida, P.F.F., Vaz, W.L.C., and T.E. Thompson. 1992. Biochemistry 31:7198-7210), suggest that non-equilibrium effects may influence lipid domain formation and membrane organization on various length and time scales. Such effects might be of importance in relation to membrane processes that require molecular mobility of the membrane components in restricted geometrical environments of the compartmentalized lipid membrane. PMID- 8519995 TI - Glycosphingolipid headgroup orientation in fluid phospholipid/cholesterol membranes: similarity for a range of glycolipid fatty acids. AB - Galactosyl ceramide (GalCer) was labeled for nuclear magnetic resonance (NMR) spectroscopy by replacement of a hydrogen atom at C6 of the galactose residue with deuterium. Wideline 2H NMR of [d1]GalCer permitted consideration of a mechanism traditionally entertained for cell surface recognition site modulation: that the nature of the fatty acid attached to the sphingosine backbone of glycosphingolipids (GSLs) importantly influences carbohydrate headgroup orientation. Comparison was made among various glycolipid fatty acids by altering hydroxylation, saturation, and chain length. Studies were carried out in unsonicated bilayer membranes mimicking several important characteristics of cell plasma membranes: fluidity, low GSL content, predominant [sn-2]monounsaturated phosphatidylcholine (PC) (1-palmitoyl-2-oleoyl PC), and the presence of cholesterol. Spectroscopy was performed on samples over a range of temperatures, which included the physiological. 2H NMR spectra of [d1]GalCer having 18-carbon saturated fatty acid (stearic acid), cis-9-unsaturated fatty acid (oleic acid), D and L-stereoisomers of alpha-OH stearic acid, or 24-carbon saturated fatty acid (lignoceric acid) were importantly similar. This argues that for GSLs dispersed as minor components in fluid membranes, variation of the glycolipid fatty acid does not provide as much potential for direct conformational modulation of the carbohydrate portion as has sometimes been assumed. However, there was some evidence of motional differences among the species studied. The 2H NMR spectra that were obtained proved to be more complex than was anticipated. Their features could be approximated by assuming a combination of axially symmetric and axially asymmetric glycolipid motions. Presuming the appropriateness of such a analysis, at a magnetic field of 3.54 T (23.215 MHz), the experimental spectra suggested predominantly asymmetric motional contributions. At the higher field of 11.7 T (76.7 MHz, equivalent to a proton frequency of 500 MHz), spectra indicated dominance by axially symmetric rotational modes. There was also evidence of some bilayer orientation in the stronger magnetic field. The unusual observation of spectral differences between the two magnetic field strengths may involve a diamagnetic response to high field on the part of some liposome physical characteristics. PMID- 8519996 TI - Effects of diacylglycerols on conformation of phosphatidylcholine headgroups in phosphatidylcholine/phosphatidylserine bilayers. AB - The effects of five diacylglycerols (DAGs), diolein, 1-stearoyl,2-arachidonoyl-sn glycerol, dioctanoylglycerol, 1-oleoyl,2-sn-acetylglycerol, and dipalmitin (DP), on the structure of lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine (4:1 mol/mol) were examined by 2H nuclear magnetic resonance (NMR). Dipalmitoylphosphatidylcholine deuterated at the alpha- and beta positions of the choline moiety was used to probe the surface region of the membranes. Addition of each DAG except DP caused a continuous decrease in the beta-deuteron quadrupole splittings and a concomitant increase in the alpha deuteron splittings indicating that DAGs induce a conformational change in the phosphatidylcholine headgroup. Additional evidence of conformational change was found at high DAG concentrations (> or = 20 mol%) where the alpha-deuteron peaks became doublets indicating that the two alpha-deuterons were not equivalent. The changes induced by DP were consistent with the lateral phase separation of the bilayers into gel-like and fluid-like domains with the phosphatidylcholine headgroups in the latter phase being virtually unaffected by DP. The DAG-induced changes in alpha-deuteron splittings were found to correlate with DAG-enhanced protein kinase C (PK-C) activity, suggesting that the DAG-induced conformational changes of the phosphatidylcholine headgroups are either directly or indirectly related to a mechanism of PK-C activation. 2H NMR relaxation measurements showed significant increase of the spin-lattice relaxation times for the region of the phosphatidylcholine headgroups, induced by all DAGs except DP. However, this effect of DAGs did not correlate with the DAG-induced activation of PK-C. PMID- 8519997 TI - Interaction of a nonspecific wheat lipid transfer protein with phospholipid monolayers imaged by fluorescence microscopy and studied by infrared spectroscopy. AB - The interaction of a nonspecific wheat lipid transfer protein (LTP) with phospholipids has been studied using the monolayer technique as a simplified model of biological membranes. The molecular organization of the LTP-phospholipid monolayer has been determined by using polarized attenuated total internal reflectance infrared spectroscopy, and detailed information on the microstructure of the mixed films has been investigated by using epifluorescence microscopy. The results show that the incorporation of wheat LTP within the lipid monolayers is surface-pressure dependent. When LTP is injected into the subphase under a dipalmytoylphosphatidylglycerol monolayer at low surface pressure (< 20 mN/m), insertion of the protein within the lipid monolayer leads to an expansion of dipalmytoylphosphatidylglycerol surface area. This incorporation leads to a decrease in the conformational order of the lipid acyl chains and results in an increase in the size of the solid lipid domains, suggesting that LTP penetrates both expanded and solid domains. By contrast, when the protein is injected under the lipid at high surface pressure (> or = 20 mN/m) the presence of LTP leads neither to an increase of molecular area nor to a change of the lipid order, even though some protein molecules are bound to the surface of the monolayer, which leads to an increase of the exposure of the lipid ester groups to the aqueous environment. On the other hand, the conformation of LTP, as well as the orientation of alpha-helices, is surface-pressure dependent. At low surface pressure, the alpha-helices inserted into the monolayers are rather parallel to the monolayer plane. In contrast, at high surface pressure, the alpha-helices bound to the surface of the monolayers are neither parallel nor perpendicular to the interface but in an oblique orientation. PMID- 8519998 TI - Detection of temporary lateral confinement of membrane proteins using single particle tracking analysis. AB - Techniques such as single-particle tracking allow the characterization of the movements of single or very few molecules. Features of the molecular trajectories, such as confined diffusion or directed transport, can reveal interesting biological interactions, but they can also arise from simple Brownian motion. Careful analysis of the data, therefore, is necessary to identify interesting effects from pure random movements. A method was developed to detect temporary confinement in the trajectories of membrane proteins that cannot be accounted for by Brownian motion. This analysis was applied to trajectories of two lipid-linked members of the immunoglobulin superfamily, Thy-1 and a neural cell adhesion molecule (NCAM 125), and the results were compared with those for simulated random walks. Approximately 28% of the trajectories for both proteins exhibited periods of transient confinement, which were < 0.07% likely to arise from random movements. In contrast to these results, only 1.5% of the simulated trajectories showed confined periods. Transient confinement for both proteins lasted on average 8 s in regions that were approximately 280 nm in diameter. PMID- 8520000 TI - Dances with microscopes: Antoni van Leeuwenhoek (1632-1723). PMID- 8519999 TI - The myosin catalytic domain does not rotate during the working power stroke. AB - Electron paramagnetic resonance spectroscopy of a spin probe attached to cys-707 on myosin cross-bridges was used to monitor the orientation of the myosin catalytic domain at the beginning and end of the working power stroke in active muscle. Elevated concentrations of orthophosphate and decreased pH were used to shift the population of cross-bridges from force-producing states into low force, pre-power-stroke states. The spectrum of probes in active fibers was not changed by conditions that reduced tension by 70%, indicating that the orientation of the catalytic domain was the same at the beginning and end of the power stroke. Thus the data show that the catalytic domain remains rigidly oriented on the actin filament during the power stroke. PMID- 8520001 TI - bcl-2 protein in breast cancer cells obtained by fine needle aspiration (FNA): a preliminary report. AB - The bcl-2 protein plays a role in the regulation of programmed cell death (PCD), overriding apoptosis. Its expression has been reported in breast ductal cells, where it is believed to be involved in the hormonal regulation of hyperplasia and involution. To date, bcl-2 gene product has not been investigated on breast cancer FNA. The expression of bcl-2 protein was evaluated using an immunoalkaline phosphatase technique in 54 pre-operative breast cancer aspirates and in paraffin embedded sections from 20 matched surgical specimens. A high rate of bcl-2 protein expression was found on FNA samples (65%) and on the corresponding tissue sections (60%); there was a nearly absolute concordance in the two specimens, with 19/20 (95%) cases showing a concordant staining. These findings concur with the view that bcl-2 gene is frequently expressed in breast cancer, possibly through a hormonal-dependent pathway. PMID- 8520002 TI - Ki-1-positive anaplastic large cell lymphoma initially diagnosed as Hodgkin's disease by fine needle aspiration (FNA) cytology. AB - A 45-year-old male presented with a large mass in the left axilla. FNA cytology was interpreted as Hodgkin's disease (HD), lymphocyte depletion (LD) type, but histopathologic and immunohistochemical examination showed features of Ki-1 positive anaplastic large cell lymphoma. Unrepresentative sampling by the FNA from the tumour periphery resulted in a false impression of dual reactive and neoplastic cell populations, which together with the frequent Reed-Sternberg-like cells led to the initial erroneous impression of HD. Therefore, the cytologic diagnosis of HD, LD should be approached with caution. PMID- 8520003 TI - Fine needle aspiration (FNA) in the diagnosis of soft tissue tumours; a review of 22 years experience. AB - FNA plays an important role in preoperative diagnosis of soft tissue tumours. A close clinical/morphologic cooperation is essential. FNA should be performed on the most accessible part of the tumour, avoiding penetration of the deep portions of the tumour. Needles 0.7 mm (22 G) are recommended. For deep lesions, needles with a stylet should be used. After the FNA, tattooing of the aspiration channel is recommended, and the channel is surgically removed together with the tumour, if a sarcoma. Material from the FNA can be used for additional examinations, i.e. electron microscopy, immunohistochemistry, DNA ploidy analysis and chromosomal analysis. Those techniques are of great importance in the differential diagnosis, particularly in the paediatric small/round cell tumours. The majority of sarcomas can be defined as low grade or high grade malignant in FNA. For malignancy grading the following parameters are used: cellularity, pleomorphism, chromatin pattern, nucleolar structure, mitotic figures and necroses. Cytodiagnostic details of the most common soft tissue tumours and their differential diagnoses are presented. PMID- 8520004 TI - Fine needle aspiration (FNA)-induced necrosis of tumours of the thyroid. AB - Two cases of necrosis of thyroid oxyphilic tumours following FNA are reported. The first patient received surgery 4 weeks after FNA and histological examination revealed an encapsulated and totally necrotic tumour 2 cm in diameter. In the second patient surgery was performed after 25 days. Histological examination showed a 0.7 cm diameter tumour consisting mainly of fibrous tissue with residual oxyphilic tumour cells only in a small peripheral rim. In both patients no capsular or vascular invasion and no blood vessel thrombosis were present. A review of the literature revealed that oxyphilic tumours are susceptible to post FNA necrosis, which might be due to the compromised vascular supply after FNA in conjunction with the intrinsic energy deficiency of oncocytic tumour cells. PMID- 8520005 TI - Formation of bile canaliculi in long-term primary cultures of adult rat hepatocytes on permeable membrane: an ultrastructural study. AB - Adult rat hepatocytes were cultured for 15 days on type I collagen-coated permeable membranes in a hormonally defined Waxman's modified medium supplemented with very low concentrations of insulin, glucagon and dexamethasone. Phase contrast examination showed that 15-day-old cultures still formed a regular monolayer of polygonal cells. In similarly aged cultures, intracellular glycogen was abundant and evenly distributed, while steatosis remained very limited. Scanning and transmission electron microscopy showed that well developed bile canaliculi could be observed on the lateral side of the hepatocyte membrane after 4 days of incubation and persisted for 2 weeks. These canalicular structures probably originated from coalescence of membrane invaginations observed in 1-day old cultures. Transmission electron microscopy showed that the ultrastructure of the cells was very close to that of normal rat hepatocytes in the intact liver. These results suggest that rat hepatocytes cultured under these experimental conditions are able to develop and maintain tissue-specific cytochemical and morphological properties for at least 15 days. PMID- 8520006 TI - Urine cytology evaluation in cases of uretero-ileal cutaneous diversion. AB - Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. The cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high. PMID- 8520007 TI - The diagnosis of extraskeletal myxoid chondrosarcoma by fine needle aspiration. PMID- 8520008 TI - Addison's disease caused by adrenal blastomycosis: a case report with fine needle aspiration (FNA) cytology. PMID- 8520009 TI - Diagnostic value of the examination of clots in cytology. PMID- 8520010 TI - Schistosoma haematobium infection and papilloma of the bladder in a European patient. PMID- 8520011 TI - [Current review of the treatment of reflux esophagitis and its complications]. PMID- 8520012 TI - [Nitric oxide in gastroenterology]. AB - Identification of so called endothelium derived relaxing factor, EDRF, as nitric oxide, ON, produced in situ in digestive tract, as well as in many other organs, offers the possibility of pharmacologic control blocking or stimulating its production in situ. Theoretically, conditions like achalasia, cell injury by endotoxins, altered visceral arterial flow, hyperdynamic circulatory state in decompensated cirrhosis, protein synthesis and glomerular filtration in ascites, will be amenable of better treatment. This gas is considered as labile humoral like messenger, mediator or a regulator of cell function in a number of physiological are promising. By now most of the information available comes from animal studies. PMID- 8520013 TI - The role of endoscopy in biliary obstruction. PMID- 8520014 TI - [Portal hypertension and splenic circulation]. AB - The severe complications of portal hypertension have not been solved yet, except the majority of cirrhotic livers suffering of hemorrhagic varices which are expected to be managed by a liver transplant. When we started to study post operatively our patients operated on with the porta azygous disconnection in whom we ligate the splenic artery and the short vessels with the technique we described in 1981, we found that the patients subject to this procedure have no alterations in their splenic circulation. An anatomic research study determined that the spleen is also irrigated by the left gastroepiploic artery which it has not been described before. This finding simplifies our surgical disconnection procedure because now it is not necessary the ligation of the splenic artery. PMID- 8520015 TI - [Colostomy in anal, rectal and sigmoid surgical pathology]. AB - Colostomy features in anal, rectum, and sigmoid pathology and surgery are here detailed. Problems for the patient and the physician, surgical indications, techniques, permanence, stoma clubs and complications, are outlined. PMID- 8520016 TI - [Four decades since the beginning of Experimental Gastroenterological Surgery at the Peruvian University]. AB - The historic evolution of Peruvian Surgery up to the application of experimentation is described, guiding it on a scientific path. It is evident that the beginning of Experimental Surgery and Laboratories were established, four decades ago, in Peruvian Universities; this enabled other surgical center to introduce new surgical procedures to medical practice. The first experiments in gastrointestinal surgery performed by a surgical school of the UNMSM and in the UPCH as well as their clinical applications in two Teaching Hospitals (Loayza and Cayetano Heredia) are reviewed. PMID- 8520017 TI - [Helicobacter pylori and gastric cancer]. AB - A review is done on the evidence in favor of a link between Helicobacter pylori infection and gastric cancer of the intestinal type. In countries at high risk of gastric cancer, like Peru, Hp infection begins early in life and is highly frequent and persistent. When Hp colonizes the gastric mucosa, it causes active chronic gastritis. Initially, the gastritis is of the superficial type. With time, and probably as a result of the concurrent action of nutritional, epidemiologic and immunologic modulating factors, chronic superficial gastritis may give rise to a progressive gastric pathology that leads to gastric premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia of the gastric mucosa) and increases the predisposition to gastric cancer. The principal modulating factors are described. The epidemiology of gastric premalignant lesions in Peru is also described. Finally, a discussion is done on the effect that eradication of Hp infection might have on the prevalence of gastric cancer. PMID- 8520018 TI - [Role of Helicobacter pylori (HP) in digestive pathology]. PMID- 8520019 TI - [Upper gastrointestinal bleeding]. PMID- 8520020 TI - [Concepts related to the course of gastric cancer]. AB - It is difficult to precise when the diverse phenomenons that precede Gastric Cancer start. Diverse events occur in between from the genetic alternations to the advanced gastric carcinoma: inflammatory changes like gastritis, erosions, ulcerations, hyperplasia and benign neoplasias as the adenomas. On these lesions, dysplasia and later on early gastric carcinoma are established. These events have been observed and interpreted, some times in an outstanding way, by diverse authors. The current concept of the link between dysplasia and early gastric cancer is irrefutable. PMID- 8520022 TI - [Massive lower digestive bleeding]. AB - Lower digestive bleeding is the bleeding distal to the ligament of Treitz and ranges from occult loss to massive hemorrhage. Acute and massive form represents about 20% of all gastrointestinal acute bleeding. In children and young patients the most frequent causes are juvenile, polyps Meckel diverticula, and intussusception; in adult ages are the diverticular disease of colon, angiodysplasia and neoplasia; we must include also the intestinal TBC, typhoid fever, and intestinal amebiasis. The first aim in the management of this acute syndrome is the treatment of the hypovolemic shock; when the patient is well resuscitated, the diagnosis of the cause of hemorrhage will start using the clinical history and physical examination, proctosigmoidoscopy, emergency colonoscopy and/or angiography, or scintigraphy with 99mTc-labeled red blood cells. Definitive therapy include endoscopic an angiographic methods, or the emergency surgery. Mortality is 11% to 21%. PMID- 8520021 TI - [Treatment of Helicobacter pylori infection: current status]. AB - Considering the etiopathogenic relationship of the stomach infection by Helicobacter pylori with some gastrointestinal disease like peptic ulcer, chronic active gastritis and probably gastric cancer, it is worthwhile to consider treatment of this infection at least in some special cases; peptic ulcer (specially duodenal ulcer) with frequent recurrences, and chronic active gastritis with severe dysplasia. It has been demonstrated worldwide that there is an enormous amount of infected patients. For this reason, the development of an oral vaccine probably potentiated with helper elements such as the choleric toxin, would be ideal. Meanwhile, different therapeutic approaches, most of which are analyzed in this paper are available. At present the pharmacologic agents having demonstrated more effectively are bismuth and clarithromycin, whose action may be potentiated by the use of the proton pump inhibitors, mainly omeprazole. Satisfactory results have been reported by the use of these three agents combined for one week. Previous schemes using triple and quadruple therapy for 14 years have given similar results. Therefore, it seems that the 7-day treatment schemes are going to be recommended for a while. As long as the bacteria is eradicated, there is a possibility of recurrence. A wide range of percentages of recurrence in different countries has been reported. In general, industrialized countries the percentages does not exceed 20%. In Peru, the percentage of recurrence is as high as 73%. In these cases, we suggest the use of periodic treatment (twice a year) should the infection recur. PMID- 8520023 TI - [Chronic hepatitis]. AB - Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results. PMID- 8520024 TI - [Hemorrhage caused by rupture of esophageal varices: sclerotherapy, elastic ligation or a combination of both?]. PMID- 8520025 TI - [Laparoscopy: past, present and future]. PMID- 8520026 TI - The Src and Csk families of tyrosine protein kinases in hemopoietic cells. AB - There is increasing evidence that the Src family of cytoplasmic tyrosine protein kinases is involved in the signal transduction of antigen receptor- and Fc receptor-mediated cellular activation. This function relates at least in part to the ability of Src-related enzymes to phosphorylate conserved tyrosine-based motifs in the cytoplasmic domains of the antigen and Fc receptors. The catalytic function of Src-like products is repressed by phosphorylation of a conserved carboxy-terminal tyrosine residue, which is mediated by another cellular tyrosine protein kinase, p50csk. Based on this property, it is postulated that Csk is a potent negative regulator of antigen and Fc receptor signalling. The balance between the actions of Src-related kinases and the p50csk is likely a major determinant of immune responsiveness. PMID- 8520027 TI - The Syk/ZAP-70 protein tyrosine kinase connection to antigen receptor signalling processes. AB - The T- and B-cell receptor (TCR and BCR) signal transduction processes involve a coordinated interplay between two classes of non-receptor protein tyrosine kinases (PTKs), the Src-family and the Syk/ZAP-70 family of PTKs. Following antigen-receptor stimulation, the Src-family of PTKs mediate the phosphorylation of tyrosine residues contained in a signalling motif localized in the TCR and BCR subunits. The phosphorylation of this signalling motif recruits the Syk/ZAP-70 family of PTKs into the antigen receptor complex. This mechanism requires the tandem SH2 domains in ZAP-70 complexing to two critically spaced phosphotyrosine residues within the signalling motif. The clustering of Syk/ZAP-70 and cross-talk between this family and the Src-PTKs regulates subsequent signalling events that lead to a variety of cellular responses, such as antibody secretion, lymphokine production, cytolytic activity, proliferation, differentiation and cell survival. PMID- 8520028 TI - The Btk subfamily of cytoplasmic tyrosine kinases: structure, regulation and function. AB - The genetic defect associated with two closely related primary immunodeficiencies was recently identified as a deficiency of function of a new cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk). Btk and related genes expressed primarily in hematopoietic cells (Itk, Tec, Drsrc28C and Txk) comprise a new subfamily of cytoplasmic tyrosine kinases. These proteins share significant structural and sequence homology including an amino-terminal pleckstrin homology (PH) domain not present in other cytoplasmic tyrosine kinase subfamilies. This domain plays an essential role in regulation and function of the Btk subfamily proteins. Genetic evidence supports a critical role for Btk in B-lineage development. Additional studies demonstrate activation of these proteins in multiple hematopoietic signaling pathways including the B cell antigen receptor, several cytokine receptors, and a potential novel role in heterotrimeric G protein associated receptor signaling. PMID- 8520029 TI - The Janus protein tyrosine kinases in hematopoietic cytokine signaling. AB - Cytokines regulate cellular functions through their interaction with members of the cytokine receptor superfamily. These receptors couple ligand binding to induction of tyrosine phosphorylation through their association with the Janus protein tyrosine kinases (Jaks). Receptor dimerization induces Jak homo- or hetero-associations, autophosphorylation and activation of Jak catalytic activity. The activated Jaks are hypothesized to phosphorylate the receptors as well as a number of proteins involved in cellular signaling including SHC, the p85 subunit of PI 3-kinase, Vav and members of the Signal Transducers and Activators of Transcription (Stats) family of transcription factors. Receptor phosphorylation also allows association of hematopoietic cell phosphatase with the receptor complex, resulting in its down-regulation. Receptor mutants have allowed the identification of specific domains that are required for each function and their correlation with biological responses. PMID- 8520030 TI - Abl tyrosine protein kinase. AB - Mammalian c-Abl belongs to an evolutionary conserved family of non-receptor tyrosine kinases. It is distributed both in the cytoplasm in association with F actin, and in the nucleus where it binds chromatin. The normal function of c-Abl is poorly understood. Nevertheless, there has been rapid progress in the characterization of the structural features, signal transduction pathways, substrates and ligands involved in the action of c-Abl and Abl-derived oncogenes. These developments suggest that several mechanisms co-operate to allow regulation of normal cell growth by c-Abl and induction of leukemias by Bcr-abl. PMID- 8520031 TI - Receptor tyrosine kinases and the regulation of hematopoiesis. AB - The ongoing production of mature blood cells during the lifetime of an animal is vital for survival. Hematopoiesis is the complex process whereby a small population of pluripotential stem cells give rise to mature cell types with specialized functions. The development of mature blood cells proceeds in a hierarchical fashion originating from a self-renewable stem cell population that gradually becomes committed to lineage-restricted differentiation. Two major themes concerning the regulation of hematopoiesis have emerged. First, the proliferation, survival and differentiation of immature progenitor cells depends on extracellular signals produced by cells within the hematopoietic microenvironment. Second, protein tyrosine phosphorylation is the major biochemical mechanism by which the extracellular signals are transmitted and interpreted. In this review we will concentrate on the role of receptors with intrinsic tyrosine kinase activity (RTKs) in hematopoietic regulation. RTKs form part of a highly conserved signaling mechanism that plays an important role in the development of evolutionary diverse organisms. During hematopoiesis, RTKs are a central component of the mechanism by which hematopoietic stem cells receive extracellular signals and interpret these signals to direct the lineage restricted differentiation of multipotential progenitors. In addition, RTKs may also play an important regulatory role in the ontogeny of the hematopoietic system during embryonic and fetal development. Taken together, RTKs are an important component of the mechanisms that regulate the development and behavior of hematopoietic stem cells. PMID- 8520032 TI - Positive and negative regulation of leukocyte activation by protein tyrosine phosphatases. AB - Many of the initial signal transduction events essential for eliciting an immune response are controlled by the concerted action of protein tyrosine kinases and protein tyrosine phosphatases. However, positive or negative regulation of the cellular response does not fall exclusively into the domain of either class of enzymes. Rather, distinct enzymes can be either positive or negative regulators of a molecular reaction and in certain circumstances, it is conceivable that a single enzyme may have both functions. The biological functions of two protein tyrosine phosphatases, SHP and CD45, serve to illustrate the dichotomy by which this class of enzymes regulate immune responses. PMID- 8520033 TI - Comparison of therapeutic activity of fluconazole and itraconazole in the treatment of oesophageal candidiasis in AIDS patients: a double-blind, randomized, controlled clinical study. AB - The aim of this study was to assess the role and therapeutic efficacy of two azole antifungal drugs, fluconazole and itraconazole, in the treatment of endoscopically-diagnosed Candida oesophagitis in patients with Acquired Immunodeficiency Syndrome (AIDS). The study considered 120 Human Immunodeficiency Virus (HIV)-positive patients (67 males and 53 females, mean age 27 +/- 5) at their first episode of oesophageal candidiasis diagnosed by endoscopy (Kodsi's grade II endoscopic classification). The patients were double-blindly randomized into 2 groups of 60 patients each according to the pharmacological therapy administered: a) the patients in the first group received fluconazole (100 mg b.i.d. per os); b) the patients in the second group received itraconazole (100 mg b.i.d. per os). In order to evaluate the efficacy of the pharmacological therapy, a clinical examination was performed every week up to the end of the follow-up period (2 months); endoscopic examination was performed at the end of pharmacological treatment (3 weeks). All patients selected for the study gave their informed consent. Complete remission of endoscopic lesions was observed in 45 patients (75%) in the fluconazole group and in 23 patients (38%) in the itraconazole group (p < 0.001); partial remission of endoscopic lesions was observed in 15 patients (25%) in the fluconazole group and in 28 patients (47%) in the itraconazole group (p < 0.05). No response was observed in 9 patients (15%) in the itraconazole group. Complete clinical remission was observed in 47 patients (78%) in the fluconazole group and in 44 patients (73%) in the itraconazole group (p = n.s.); partial clinical remission was observed in 13 patients (22%) in the fluconazole group and in 12 patients (20%) in the itraconazole group (p =- m.s.). No clinical response was observed in 4 patients (7%) in the itraconazole group. No side-effects worthy of note were observed in the patients of either treatment group. The results of this study demonstrated that fluconazole is associated with higher rates of endoscopic and clinical cure than itraconazole, with a statistically significant difference as regards endoscopic cure. Both drugs appear to be safe and well tolerated. Nevertheless, further controlled clinical investigations are needed to improve our knowledge of the therapeutic action of antifungal drugs in the treatment of Candida oesophagitis in HIV disease. PMID- 8520034 TI - Case control study of risk factors for hepatitis A: Naples 1990-1991. Hepatitis Collaborating Group. AB - An increased incidence of hepatitis A was observed in Naples from 1990-1991. A hospital-based case-control study was carried out to evaluate the relative importance of various risk factors. A hundred and ninety-eight cases and 238 hospital controls were recruited during the study period. The strongest association was contact with a jaundiced person among children. A correlation was also shown for children and adults with raw shellfish consumption and pre-school nursery attendance or presence in the household of children attending pre-school nurseries. History of travel and intravenous drug use were risk factors for adult subjects. Considering the relative importance of the specific risk factors we found that 38% of the acute hepatitis A cases were attributable to contact with a jaundiced person, 15% to presence in the household of children attending pre school nurseries and 28% to raw shellfish consumption. PMID- 8520035 TI - Long-term (over 22 years) follow-up of four familial cases of Caroli's disease. AB - The authors report a long-term (over 22 years) follow-up of four familial cases, 1 brother and 3 sisters, affected by classic Caroli's disease. The male patient experienced acute cholangitis at the age of 6 and 1 of the 3 sisters at 12 years. The other two sisters were asymptomatic at the time of diagnosis. At the last control, all the patients were alive and have remained symptom-free for more than 22 years. Nevertheless, some data suggest a slowly evolving impairment of the disease even in the absence of a clinical expression. In this paper, the ways in which Caroli's disease is inherited and managed are also discussed. PMID- 8520037 TI - Intestinal absorption of bile acids: effect of ursodeoxycholic acid treatment. AB - Absorption of bile acids by diffusion occurs in all parts of the intestine whereas the active transport is only located in the terminal ileum. Absorption of ursodeoxycholic acid (UDCA) in the small intestine is slow and incomplete due to the poor solubility of this bile acid. After oral administration, UDCA competitively inhibits the absorption of endogenous bile acids in the ileum. This effect leads to changes in bile acid metabolism which may be related to its beneficial effect in cholestatic diseases. PMID- 8520036 TI - Liver targeting of adenine arabinoside monophosphate (ara-AMP) by coupling to lactosaminated human serum albumin. AB - Adenine arabinoside monophosphate (ara-AMP) is a potent antiviral agent against hepadnaviruses but its use in the treatment of chronic hepatitis B is hampered by severe neurotoxic side effects, which are dose dependent. In order to reduce these adverse reactions and to adopt the lysosomotropic approach to antiviral chemotherapy, ara-AMP was coupled to lactosaminated human serum albumin (L-HSA), a neoglycoprotein which specifically penetrates hepatocytes. In mice with Ectromelia virus hepatitis, ara-AMP coupled with L-HSA was selectively delivered to liver cells in which it was released in a pharmacologically active form. Moreover in woodchucks with WHV hepatitis and in patients with chronic HBV infection, coupled ara-AMP inhibited hepadnavirus replication at a dose (1.5 mg/kg/day) 3-6 times lower than the free drug. A clinical study using a 28-day period of treatment with conjugated ara-AMP at 1.5 mg/kg/day has now been started. In the first 6 patients the treatment has been completed. The conjugate inhibited virus growth without producing any side effects. L-HSA-ara-AMP conjugate must be given by intravenous infusion. New hepatotropic conjugates of ara-AMP have been recently prepared which could be administered by bolus intravenous injection or by intramuscular route. These complexes might assure a better compliance in patients with hepatitis B virus infection for a long lasting liver targeted antiviral treatment. PMID- 8520038 TI - Ileo-rectal anastomosis in ulcerative colitis: results of a long-term follow-up study. PMID- 8520039 TI - [Validity of scores calculated from the results of a food frequency questionnaire]. AB - To study the validity of three evaluative scores (Balance score, Vegetable score, Dietary habit score) calculated from the results of a food frequency questionnaire, the frequency of food selections from various food groups and other dietary habits were investigated in 308 female students aged 18-19 using a specially structured questionnaire. In addition, a quantitative nutrient survey with values indicated by weight was performed on each participant. (1) Balance score, Vegetable score and Dietary habits score appeared to be useful indicators for estimation of nutrient intake, vegetable intake and dietary habits, respectively. (2) Analysis showed that nutrient intake can be estimated more distinctly by the simultaneous use of balance score and dietary habits score. PMID- 8520040 TI - [Health personnel staffing requirements for health examination for the age of 1 1/2 in municipalities in Japan]. AB - Municipalities in Japan offer health education, health counseling, health examination, and home visit services for each development stage of children and for their mothers. In order to determine personnel staffing requirements for the health examination for the age of 1 1/2 as of 1989, data from a questionnaire survey in 1990 conducted by the Ministry of Health and Welfare, was analyzed. Questionnaires were sent to all municipalities and there were 3,198 responses for the response rate of 97.9%. Results showed that in 1989, 98.9% of the 3,012 municipalities were able to independently perform health examinations for 1 and half year old, and in only 0.9% these examination were performed by clinical hospitals. In the large cities designated by the Government, the health personnel system adequately supported these health examination. However due to lack of health personnel, rural towns and villages with small populations required public health nurses to be assisted by other staff, such as health workers or volunteers. And particularly they required help by public health nurses from prefectural Health Centers. For example, in those areas with populations less than 3,000, 53% of the total volume of the work required to be performed by public health nurses during the health examination had to be covered by assistance from prefectural public health nurses. While in cities with more than 300,000 population large numbers of health personnel were assigned to examinations of children, the large number of children processed resulted in inadequate time for each child/mother pair. Further study of quality levels of the examinations need to be performed. PMID- 8520041 TI - [Surveillance of hyperlipidemia among young adults in an occupational setting]. AB - This study was conducted to contribute to the improvement of occupational health surveillance. The subjects of the study were 461 young male workers born between April 1959 to March 1969, who worked at two plants in Tokyo, and who do not usually undergo examination of blood lipid levels at a routine health check-up program. The screening procedure was mainly based on the second report of the National Cholesterol Education Program Expert Panel (Adult Treatment Panel, ATP II). The proportion of the subjects with low HDL-cholesterol level (< 35 mg/dl) was 5.2% for workers in their late twenties (W20) and 8.4% for those in their early thirties (W30). For high LDL-cholesterol (130+ mg/dl), the proportion (underestimated due to non-fasting blood collection) was 7.2% for W20 and 13.5% for W30, and the difference was statistically significant (p < 0.05). Among subjects with low HDL, the proportion of subjects with total cholesterol (TC) being < 200 mg/dl was 94% (15/16) for W20 and 54% (7/13) for W30. This implies that it is difficult to detect subjects with low HDL from values for TC only especially among W20. Hence it is useful to examine HDL in combination with TC. Among subjects with TC being 200-239 mg/dl, the proportion (underestimated) of the subjects with high LDL was 40% for W20 and 26% for W30, and ATP II procedure would fail to incorporate most of them into a treatment program. Thus, accurate estimation of LDL is necessary for subjects with TC being 200+ mg/dl. Relationships of high HDL (60+ mg/dl) to exercise as well as low HDL to obesity (p < 0.05) were found among both age groups. The high prevalence of LDL and HDL abnormality found among the study subjects would imply that it is necessary to initiate evaluation of hyperlipidemia at younger ages and also ATP II procedure needs to be modified for proper surveillance. PMID- 8520042 TI - [The structural analysis of inpatient medical cost of the aged in 81 secondary medical areas of 12 Prefectures in Japan]. AB - In order to understand the structure of the per capita medical care expenditure of inpatients aged 70 years and over, correlational and principal component analyses were performed using several medical cost indices for fiscal 1991 in 81 secondary medical areas of 12 prefectures. Requests were sent to all of 777 municipalities in the 12 prefectures, and there were 763 responses for the response rate of 98.2%. A total of 1,647,187 residents who had been inpatients based on receipts for inpatient medical care expenditure were surveyed. There were 389,456 who responded that they had been inpatients at least once in the preceding 12 months, in 1991. The main results were as follows: 1) Of the residents aged 70 and over, 32.0% of men and 29.7% of women surveyed had at least one episode of hospital admission in the preceding 12 months in 1991. 2) Large differences in the medical care expenditure per inpatient per year for those aged 70 years and over exist in the secondary medical areas in 12 prefectures. 3) In both sexes, per capita expenditures for inpatient care per year are positively correlated with the bed-days in hospitals per inpatient per year, the bed days per receipt, the medical care expenditure per receipt, and the number of receipts per inpatient per year. On the other hand, for women it is negatively correlated with per capita medical care expenditure per day, but it is not statistically significant. 4) The medical care expenditure per inpatient per day is significantly negatively correlated with bed-days in hospital per receipt, the number of receipts per inpatient per year, bed-days in hospital per inpatient per year for both sexes. On the other hand, it is significantly positively correlated with medical care expenditure per receipt for both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520043 TI - [Characteristics of participants in community-based rehabilitation programs and their levels of independence in activities of daily living]. AB - To clarify characteristics of participants in community-based rehabilitation programs provided by local municipalities (cities, towns, and villages) and effect of the program on their levels of independence in activities of daily living (ADL), a cross-sectional study was performed on 422 participants in 49 municipalities in Kochi Prefecture. 1. Mean age of participants was 68.3 +/- 9.0, and 77.7% of them were stroke patients. 2. The mean interval between disease onset and program participation was 40.4 months, and the mean duration of program participation was 54.5 months. 3. At the start of rehabilitation programs and at the time of the investigation (December 1993), about 90% of the participants had good levels of independence in ADL (Rank A and over according to the standard of the Ministry of Health and Welfare). 4. The frequency of rehabilitation programs and the presence of occupational therapists were positively associated with the improvement of levels of independence in ADL. In particular, the frequency of rehabilitation programs was associated with improvement of quality of life in self-supporting participants (Rank J2), and the presence of occupational therapists was associated with the improvement of ADL in semi-bed-ridden participants (Rank A). 5. After adjusting for age and sex, using multiple logistic regression analysis, type of diseases (non-stroke), hospital rehabilitation immediately after onset, higher levels of independence in ADL at the start of rehabilitation programs, and higher frequency of rehabilitation programs were significantly associated with improvements in levels of independence in ADL. Shorter interval between disease onset and program participation, and the presence of occupational therapists were also associated with improvements in levels of independence in ADL, although the relation did not reach statistical significance. PMID- 8520044 TI - [Social activities in the elderly]. AB - In order to clarify the status of social activities in the elderly, and to investigate an association between social activities and age, ADL, and geographical area, a self-administered questionnaire survey was conducted on the aged population in four areas in Japan. Social activities was defined as "activities which required contact with society" and was measured by 4 major facets of social activity, which were based on 21 questions on job activity, socially-related activities, learning activities, and personal activities. A total index was also developed by summarizing the 4 major facets as an indicator of whether the elderly is socially active or not as a whole. The following major findings emerged from this survey: (1) Rank correlation coefficients between each item which comprised 4 major activities were relatively high; (2) Excluding two activities, "shopping" and "attending senior school", aged men were more actively involved than women; (3) Trend in degrees of social activities differed by age among the 4 major facets, i.e., (a) job activity decreased with age, (b) socially related activities and learning activities increased up to about 75 years old, and decreased thereafter, (c) personal activities were unaltered up to about 80 years old, and then decreased, and; (4) The elderly with low ADL had the lowest representation among the "highly active" in 4 major facets and total index as well. PMID- 8520045 TI - [Relationship of physical condition and functional capacity to depressive status in person aged 75 years]. AB - The purpose of the present study is to examine cross-sectionally and longitudinally the relationship of physical conditions and functional capacity to depressive status in the elderly. Subjects comprised 308 men and women aged 75 years and over living at home in a rural community. Geriatric Depression Scale (GDS) was employed to assess depressive status, and physical conditions and functional capacity were simultaneously investigated. The results obtained were as follows; 1. There was no significant difference in GDS score by age or sex. 2. Cross-sectionally, the depressive status was significantly associated with weakened grip strength and poor locomotion in men, and it was associated with experience of falls, poor chewing ability, and low levels in high functional capacity as measured by the TMIG Index of Competence. 3. Longitudinally over a 2 year period, bereavement, decline of locomotion, and persistent anxiety about physical conditions significantly influenced aggravation of the depressive status in men. In women, high systolic blood pressure and visual and/or hearing impairment influenced the aggravation. Decline in functional capacity as measured by the TMIG Index of Competence appeared to influence the aggravation in both men and women. PMID- 8520046 TI - [A case study on the process of establishing a health-related self-help group in a community in the USA]. PMID- 8520047 TI - [Allergy histories of Brazilian residents of Japanese descent in Japan]. AB - A questionnaire written in Portuguese was administered from December 1993 to February 1994 to study the frequency of allergic symptoms among Brazilians of Japanese descent in Japan. The results obtained were as follows. 1) The frequencies of allergy histories were 18% for allergic rhinitis, 14% for atopic dermatitis, 12% for alimentary allergy, 10% for allergic conjunctivitis, 9% for allergy to metals, 8% for drug allergy, 7% each for urticaria and pollinosis, and 5% for asthma. 2) The frequencies of allergic rhinitis, allergic conjunctivitis, pollinosis, urticaria and drug allergy were higher among those who came from metropolitan districts in Brazil with severe environmental pollution compared to those who came from rural districts. 3) The characteristics of persons who had subjective symptoms of pollinosis in early spring during their stay in Japan were as follows: The districts they resided in while in Japan were in the Kanto area where the frequencies of Japanese-cedar pollen-specific IgE antibodies positives were high and also where the frequencies of Japanese cedar pollinosis were high among Japanese living in Japan. The districts they originally came from were the metropolitan areas in Brazil, and they were resident in Japan for more than one year. PMID- 8520048 TI - [Effect of body weight reduction on blood pressure and biochemical data]. AB - The purpose of this study was to investigate the relation between body weight reduction and some complications associated with obesity. The subjects were 248 middle-aged obese persons (male 37, female 209) who participated in a weight reduction program at the Aichi Prefectural Center of Health Care from 1983 to 1990. The subjects had no severe complication, and the obesity indexes of all of them were over 120%. The program was held monthly for five months and consisted of diet (1500 kcal/day) and exercise (10000 walk steps/day). After the program, mean obesity index decreased by about 9%, and mean body weight reduction was about 5kg. Blood pressure, total cholesterol, triglyceride and GPT were significantly decreased, and HDL cholesterol was slightly increased. For each item the percentage of persons with abnormal values reduced by about 5 to 20%. From the relationship between degree of decrease of obesity and changes of the values of each item, it was estimated that some complications of obesity require greater than 5 to 10% decrease in obesity index to be affected. The value of each examination item before the program and the degree of decrease of obesity index had an effect on changes of the values, but obesity index before the program and age had little effect. PMID- 8520049 TI - [Exposure to blood during midwifery operations--a questionnaire study]. AB - A self-administered questionnaire was mailed to all midwives working in Nara Prefecture to investigate blood exposure events at delivery and to consider protective measures for the exposure. Out of the 203 midwives 193 responded to the questionnaire. The median number of deliveries in which the midwives had assisted within the past one year was 35 after excluding those who had not assisted in deliveries at all. The incidence of needle-stick injuries was estimated to be 86.2 per 100 persons within the past one year. The occurrence in the subgroup who had worked as midwife for less than 5 years was 2-3 times higher than that in those who worked for more than 5 years. Over 90% of the midwives had experiences of direct blood contact events to the skin while assisting in their 10 most recent deliveries. Blood contact events occurred in the finger-hand-arm area in 85% of the midwives, on the legs in 62%, in the face in 20% and in the eyes in 1%. Around 20% of the midwives had unintentionally sucked amniotic fluid when using a tracheal catheter on a newborn. The most common occasion where direct blood contact events occurred was while bathing an infant for removing blood and amniotic fluid. The midwives wore a disposal gown more often when assisting in labors of parturient women infected with blood-born infectious diseases than without the diseases, and similarly for wearing gloves when measuring blood loss and for usage of a mechanical device for sucking amniotic fluid in the tracheae of an infant. Based on the results obtained in this questionnaire study and our previous study about blood contact events observed in a delivery room, protective measures for midwives against exposure to blood at delivery are required and some ideas are presented. PMID- 8520050 TI - [Relationships between atmospheric Sugi (Japanese cedar)-pollen counts and indices of climatic conditions]. AB - Atmospheric pollen surveys have been conducted using Durham's standard sampler for 12 years in Toyama Prefecture. The relationships between Sugi (Japanese cedar, Cryptomeria japonica D. Don) pollen and some indices of climatic conditions were analyzed. The results were as follows: 1. Total pollen counts showed a tendency to increase for 12 years, although the variation of the count was relatively large. 2. Significant correlations were found between pollen counts and some indices of the climatic conditions in July of the previous year, such as duration of sunshine, mean daily temperature and daily maximum, as well as minimum temperature. 3. Significant correlation was found between pollen count and duration of sunshine in January and March, and the amount of snowfall in March of the observed year using multiple regression analysis. Pollen counts were shown to be relatively high in years with short sunshine in January and long sunshine and heavy snow in March. PMID- 8520051 TI - [A comparative study of public knowledge and awareness of echinococcus in relation to anti-echinococcus policies of towns in Hokkaido]. AB - A population-based comparative study was performed on public awareness and knowledge about the risk of Echinococcosis and the life habits of the people living in 2 towns in eastern Hokkaido, Bekkai and akan. Bekkai has had an anti echinococcosis policy and Akan has only limited experiences with such countermeasures. The results of the survey were as follows: 1) Compared with the inhabitants in the town of Akan, the residents in Bekkai had significantly higher correct response rates for many questions concerning parasitological knowledge and the risks of echinococcosis, and knew about subjects such as the pathogen, latency period, susceptible organs, the prognosis, the possibility of transmission of echinococcosis from human to human and methods for the sterilization of eggs from infected animals. 2) The rate of correct answers to such questions were approximately 70 to 90% in both towns. However the percentage of correct answers to questions about carrier animals and the question of human susceptibility were relatively low, ie., 45% and 20%, respectively, even in Bekkai. 3) The residents of Akan knew more about carrier animals of echinococcosis than the inhabitants of Bekkai. In Akan woman and persons in their 20's and 30's had lower rates of correct answers. Further health education should be aimed toward such people. 4) Foxes appeared near private homes more frequently in Akan than in Bekkai. More inhabitants of Akan used spring water as drinking water than in Bekkai, while more inhabitants used tap water as drinking water in Bekkai. Only a few inhabitants paid attention to how to prepare vegetables for cooking. This information suggests that echinococcosis may spread in Akan in the near future. 5) Our results suggest that better organized health education programs, the extension of tap water services in Akan, and the establishment of proper methods for disposal of garbage and the afterbirth of cattle are necessary to reduce the presence of foxes in inhabited areas. PMID- 8520052 TI - [Analysis of cause of recent rise in number of foreigners reported to HIV/AIDS surveillance in Japan]. AB - HIV/AIDS surveillance in Japan experienced a sharp and transient rise in 1991-92 in the number of foreign HIV positives but not of AIDS cases, for reasons of which remain unclear. Using the national HIV/AIDS surveillance data base the cause of the increase was studied by comparing the trends of foreign cases diagnosed in 1991-92 with those in 1985-90 in terms of gender, age, nationality, clinical stage, possible route of infection, possible place where the case contracted HIV and the place where the case was identified. Present analysis revealed: (1) In 1991-92 there was a large increase in the number of heterosexually-infected female HIV positive aged below 30 years reported from the areas surrounding Tokyo, of which the majority was of Asia origin. (2) A similar but moderate change was also seen in foreign males infected heterosexually but not in those infected homosexually. These were predominantly of U.S./Europe origin, aged > or = 30 and reported from Tokyo. (3) Although most of the foreign cases reportedly contracted HIV outside of Japan, those infected in Japan began being reported in 1991-1992. These results suggest that change in foreign cases seen in 1991-1992 was not only in number but also in gender, age, nationality, route of infection and geographical distribution. This should be taken into consideration in considering the HIV/AIDS prevention strategy in Japan. PMID- 8520053 TI - [Prevalence of HIV and STD infection among foreign STD clinic attendants in Ibaragi prefecture, Japan]. PMID- 8520054 TI - Classical Kaposi's sarcoma: a survey of 163 cases observed in Bari, south Italy. AB - BACKGROUND: Classical Kaposi's sarcoma (KS) is a sporadic disease that is particularly prevalent in Mediterranean countries. OBJECTIVE: The aim of the study was to update clinical information about this rare condition. METHODS: A survey of 163 cases observed in the period 1971-1990 in Bari, South Italy, was carried out. All records were reviewed and, when lost to follow-up for more than 6 months, patients were called back to update personal and family histories. The age at onset averaged 64 years (range 18-85). The male-to-female ratio was 3:1. No familiar occurrence was identified, and no significant association was found with other conditions (i.e. second primary malignancies and diabetes mellitus). Death from KS occurred in 16 cases, at the mean age of 71 years, an average of 5.7 years after the onset of the disease. To assess whether the different clinical patterns of the disease in its earlier stages may give any indication of its subsequent clinical course, all cases were re-classified into three groups (low-, moderate- and high-eruptivity group) on the basis of both the extent and the rate of spread of the disease before first admission; group-stratified survival function was evaluated using Kaplan-Meier's life table method. RESULTS: Highly significant (p < 0.0001) differences were found in survival profiles of the three study groups, also when only deaths due to KS were computed. CONCLUSION: These findings provide some support to the hypothesis that three subsets of classical KS exist that have different prognoses and, consequently, need different therapeutic approaches. PMID- 8520055 TI - Contact hypersensitivity to corticosteroids in routine patch test patients. A multi-centre study of the Swiss Contact Dermatitis Research Group. AB - BACKGROUND: Contact hypersensitivity to corticosteroids is increasingly reported and has been identified as a problem of considerable clinical relevance. The prevalence of positive patch tests to corticosteroids ranges from 0.2 up to 5%. OBJECTIVE: The prevalence of positive patch tests to corticosteroids in Switzerland was determined in a multi-centre study of patients undergoing routine patch tests. METHODS: As representatives of corticosteroid groups, the following substances were used for screening: tixocortol pivalate and hydrocortisone for group A (hydrocortisone type), hydrocortisone butyrate for group D (hydrocortisone butyrate type) and budesonide for both groups B (triamcinolone type) and D. Patients positive for at least one corticosteroid were retested with the screening series and 12 corticosteroids commonly used in Switzerland. RESULTS: Among 3,016 consecutive patients, 65 individuals (2.2%) with a total of 106 positive reactions were found. Retesting showed a concordance of 70-98%, depending on the corticosteroid and the score of the positive reaction. In the subsequently tested corticosteroid series including 12 substances, 19 out of 56 screening-positive patients had a positive result to one or several corticosteroids. There were only few evident cross-reactive patterns in between the corticosteroids tested. CONCLUSIONS: Corticosteroids should be included in routine patch testing, because contact sensitization to a corticosteroid is of considerable practical importance. We confirm that as markers of corticosteroid sensitization tixocortol pivalate, budesonide and hydrocortisone butyrate may be suited, because there is no single corticosteroid which is a marker for all four corticosteroid groups. Patch test reactions of 2+ or higher have a better reproducibility than 1+ reactions. PMID- 8520056 TI - Altered collagen and glycosaminoglycan syntheses in familial scleroderma skin fibroblasts. AB - BACKGROUND: The main clinical symptoms of systemic scleroderma are caused by an accumulation of collagen in the tissues. Familial scleroderma is a very rare disorder in which systemic scleroderma occurs in the members of the same family. OBJECTIVE: To know whether or not the biosynthetic properties of familial scleroderma skin fibroblasts are similar to those of nonfamilial scleroderma fibroblasts, syntheses of extracellular matrix components in the two fibroblast strains obtained from familial scleroderma patients were studied. METHODS: Expression of collagen and glycosaminoglycans by cultured familial scleroderma fibroblasts was determined. RESULTS: Collagen synthesis by patient fibroblasts was elevated 1.4-fold compared with control fibroblasts. Translational activity of type I procollagen mRNA and the level of alpha 1 (I) mRNA in the patient fibroblasts was increased 1.7- and 1.6-fold, respectively. The ratio of hyaluronic acid/dermatan sulfate in the patient fibroblasts was lower than that in control fibroblasts. CONCLUSION: The results indicate that the biosynthetic phenotypes of familial scleroderma fibroblasts are similar to those of nonfamilial scleroderma fibroblasts which have already been reported. PMID- 8520057 TI - Anti-melanoma monoclonal antibody 225.28S immunoscintigraphy in metastatic melanoma. AB - BACKGROUND: Accurate staging and early detection of metastases are crucial to melanoma management. It would thus be of great value to have a widely available, cost-effective method that allows to examine the whole body and is more specific than current imaging modalities. OBJECTIVE: The purpose of the study was to assess the value of immunoscintigraphy with 99mTc-radiolabeled F(ab')2 fragments of the 225.28S monoclonal antibody in the staging of melanoma. METHODS: 29 patients with known or suspected metastases were enrolled in the study and examined by monoclonal antibody fragment scintigraphy. The results were compared to physical examination, other imaging modalities and, where available, histology. RESULTS: Antibody scintigraphy detected 9/34 metastases. There were 2 false-positive lesions. Diagnostic accuracy was 41%, sensitivity 26% and specificity 83%. CONCLUSION: 99mTc-radiolabeled F(ab')2 monoclonal antibody fragment scintigraphy cannot be recommended for staging of melanoma patients. The search for more sensitive radiopharmaceuticals for scintigraphy should thus be encouraged. PMID- 8520058 TI - Modification of late epidermal differentiation in photoaged skin treated with topical retinoic acid cream. AB - BACKGROUND: Retinoic acid (RA) cream treatment alters epidermal proliferation and differentiation in photoaged skin. OBJECTIVE: To study the changes in the expression of markers of epidermal differentiation in photoaged skin following RA cream treatment. METHODS: Ten subjects with photoaged skin were examined before treatment and at regular intervals during 12 months of once daily application of 0.05% tretinoin cream over the left forearm. Paraffin-embedded biopsy sections from the forearm were stained with loricrin, filaggrin, involucrin and cornifin antisera in addition to hematoxylin and eosin. The various layers were measured using a calibrated optical micrometer. RESULTS: The thickness of the epidermis increased rapidly, reaching a substantial increase after 1 month of retinoid cream application and retaining it during the following 12 months. The stratum granulosum achieved a transient but substantial increase after 1 and 3 months. Except involucrin, the ratio between the layers expressing the various markers of epidermal differentiation and the epidermis significantly increased following tretinoin cream treatment. CONCLUSION: RA cream treatment not only increases the thickness of the epidermis but also the programming of late terminal epidermal differentiation, as expressed by the markers studied. Thus, RA appears to affect both proliferation and differentiation of keratinocytes in vivo. PMID- 8520059 TI - Human leukocyte interferon-alpha versus podophyllotoxin in cream for the treatment of genital warts in males. A placebo-controlled, double-blind, comparative study. AB - BACKGROUND: The incidence of overt genital warts, a common sexually transmitted disease of high prevalence, has been on the rise for the last few years. The infection is caused by several types of human papillomaviruses (HPVs), some of which have been accepted as a factor in the pathogenesis of genital squamous-cell carcinomas. OBJECTIVE: The aim of this double-blind, placebo-controlled study was to compare and evidence differences in clinical efficacy and tolerance between human leukocyte interferon-alpha (2 x 10(6) IU/g) and podophyllotoxin (0.5%), incorporated in a hydrophilic cream base to cure genital warts in Asian males. METHODS: Sixty patients, circumcised, who ranged in age from 18 to 40 years (mean 25.0), diagnosed with the evidence of penoscopy and HPV DNA (Southern dot blot) as harboring 396 lesions (mean 6.6), were randomized to three parallel groups. Each subject was allocated a precoded tube (40 g) containing one of two trial preparations or matching placebo for 3 days' (consecutive) usage, thrice daily. The study lasted 16 weeks with 4 weeks of active treatment. The patients were examined on a weekly basis, and a clinically and HPV-DNA-confirmed total regression of lesions was recorded as cured. Patients cured during the treatment were spared further therapy and were requested to visit us as scheduled for poststudy follow-up. RESULTS: Findings indicated that patients treated with leukocyte interferon-alpha cream had shown comparatively better results than the podophyllotoxin-treated group (90 vs. 55%, p < 0.0285) or the placebo group (15%). Mild and transient localized erythema (8.3%), burning sensation (6.6%) and transitory increase in body temperature (> 38 degrees C; 6.6%) were the most frequent adverse symptoms with no dropout. The study was followed up for 1 year, and out of 32/60 (53.3%) cured patients 3 had a relapse after 10 months. CONCLUSION: Leukocyte interferon-alpha (2 x 10(6) IU/g) has shown comparatively better results than 0.5% podophyllotoxin and placebo in a hydrophilic cream base, thus leukocyte interferon-alpha in cream may provide an alternative and effective regimen to treat genital warts in males. PMID- 8520060 TI - NERDS syndrome: an additional case report. AB - NERDS is an eosinophilic disorder recently described by Butterfield and characterized by an association of nodules, eosinophilia, rheumatism, dermatitis and swelling. We describe an additional case, the third, of this new eosinophilic syndrome. The cardinal features included joint and cutaneous manifestations with prominent para-articular nodules and rheumatism, xerosis, recurrent urticarial eruption with angioedema associated with tissue and peripheral blood eosinophilia. A drug-induced (diclofenac) allergic rash and lymphadenopathy appeared during the course of the illness. Persistent leukocytosis with a maximum of 65% of eosinophils, mostly exhibiting the hypodense phenotype (activation index), was always present. During the acute phase of the disease, flow cytometric analysis of blood and bone marrow revealed proliferation of activated CD4+/OKDR+ T helper cells and CD25+/OKDR+ eosinophils. PMID- 8520061 TI - Hereditary hypotrichosis simplex of the scalp. AB - We report on a female aged 13 years, whose scalp hair began to disappear at the age of 9 years, leaving only sparse wispy hairs in the parietal-occipital region. Eyelashes, eyebrows and body hair were unaffected. There were no signs of ectodermal dysplasia on the skin, nails, teeth and eyes nor other congenital abnormalities. The family pedigree showed 15 relatives similarly affected according to an autosomal dominant mode of transmission. Clinical, genetic, histological and ultrastructural aspects led to a diagnosis of hereditary hypotrichosis simplex of the scalp (Toribio-Quinones type). PMID- 8520062 TI - Cycloserine-induced lichenoid drug eruption. AB - A 65-year-old male patient who has taken antituberculous drugs including cycloserine for 8 months showed multiple pruritic, violaceous, flat-topped papules and plaques on his back which had developed 5 months into therapy. Histopathologic findings were consistent with lichenoid drug eruption. Patch test with the drugs revealed a strongly positive reaction to cycloserine only. Four months after discontinuation of oral cycloserine, pruritus resolved and the lesions subsided without any new lesions. Cycloserine is one of the antituberculous drugs. Skin manifestations resulting from its administration are reported to be rare, but to our knowledge, this is the first case report of lichenoid drug eruption from its use. PMID- 8520063 TI - Tuberculosis verrucosa cutis which remained undiagnosed for forty-three years. AB - An unusual case of tuberculosis verrucosa cutis of the left lower limb in a 65 year-old woman is reported. The disease, arising on the plantar aspect of the foot in 1950, was correctly diagnosed by culture of Mycobacterium tuberculosis complex from a skin biopsy only in 1993. A spectacular improvement of the cutaneous lesions was achieved using combined therapy with isoniazide, rifampicin, ethambutol and pyrazinamide. PMID- 8520064 TI - Involutional lipoatrophy: macrophage-related involution of fat lobules. AB - Involutional lipoatrophy is an apparent idiopathic lipoatrophy with characteristic histopathologic features. We report a patient with a distant history of intramuscular injections and subsequent typical involutional lipoatrophy in whom macrophage invasion of the fat was prominent. Light microscopy revealed small, thin lobules of fat with focally prominent blood vessels and a variably hyaline background. Macrophages containing granular acid mucopolysaccharide material were present in direct apposition to lipocytes, around involuting lobules and between collagen fibers in the neighboring dermis. Focal deposits of iron were observed. Electron-microscopic examination revealed macrophages abutting lipocytes and containing lipid droplets, clear vacuoles and lysosomes in varying proportions. Lipocytes varied in size. The lipid appeared normal in most, but scattered cells contained electron-dense granules or needle shaped clefts within the lipid. We speculate that previous injections in our patient stimulated a macrophage response, with subsequent regression of lipocytes of the neighboring fat lobules. PMID- 8520065 TI - Hobnail hemangioma. AB - We report a case of hobnail hemangioma presenting as a congenital 2-mm brownish papule on the face of an 11-year-old girl. Hobnail hemangiomas have recently been characterized as a group, and they are related to the so-called targetoid hemosiderotic hemangiomas. Immunohistochemical data (positivity for factor VIII related antigen, CD-34 and CD-31) support a vascular origin. PMID- 8520066 TI - Reticular erythematous mucinosis associated with human immunodeficiency virus infection. AB - We report the case of a 56-year-old woman with reticular erythematous mucinosis (REM). During her workup infection with the human immunodeficiency virus (HIV) was detected. She developed a cerebral toxoplasmosis, salmonella sp. bacteremia and oral ulcerations with the presence of type I herpes simplex virus and cytomegalovirus. The relation of REM with the deposition of mucin in AIDS patients' bone marrow and HIV infection is discussed. To our knowledge, this is the first report where REM is associated with HIV disease. PMID- 8520067 TI - Recurrent inflammation in incontinentia pigmenti of a seven-year-old child. AB - A young girl has undergone the typical skin manifestations of incontinentia pigmenti, leaving now only discrete hyperpigmentation on the flexor sides of the lower extremities. Each time when she has a feverish infection, a recurrence of inflammation can be seen within the hyperpigmented areas. At the same time when the fever subsides, the acute skin manifestations disappear as well. The combination of recurrent inflammatory skin manifestations within the hyperpigmented skin areas of incontinentia pigmenti and fever is unique. The reasons for this phenomenon and for its strict limitation to the areas of incontinentia pigmenti remain unclear. PMID- 8520068 TI - Urticarial vasculitis induced by fluoxetine. PMID- 8520069 TI - Molluscum contagiosum in children and its relationship to attendance at swimming pools: an epidemiological study. PMID- 8520070 TI - Dermatitis herpetiformis: epidemiologic consideration from Korea. PMID- 8520071 TI - Do we really need NERDS? PMID- 8520072 TI - The 'mantle hair of Pinkus'. A review on the occasion of its centennial. AB - The 'mantle hair' is a hair follicle which is characterized by a circumferential proliferation of basaloid epithelial cells emanating from the base of its infundibulum. These cells show varying sebaceous differentiation. The mantle hair was first described 100 years ago. Since then, this type of hair follicle with its particular sebaceous gland has been forgotten repeatedly, to be rediscovered anew. Thus, a confusing terminology has evolved, and concepts of its nature are controversial. In this article we present a review of the 100-year history of the mantle hair. PMID- 8520073 TI - A Japanese case of the fibrillar type of dermatitis herpetiformis. AB - BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, this disease is very rare in Asian populations including the Japanese. METHODS AND RESULTS: We present a Japanese DH patient, who showed a fibrillar pattern of deposition of IgA, IgG, IgM and C3. The HLA typing revealed no B8/DR3. The survey of the Japanese literature and the comparison to studies on American or European DH revealed several interesting differences: high frequency of the fibrillar pattern, relatively high incidence of deposits of immunoglobulins other than IgA, rarity of gluten-sensitive enteropathy and HLA-B8/DR3 in Japanese DH. CONCLUSION: The present study suggests that there may be a significant difference in pathophysiology between Caucasian and Japanese DH patients. PMID- 8520074 TI - Subsurface imaging of living skin with optical coherence microscopy. AB - BACKGROUND: A new type of microscope has been developed for acquiring cross sectional images of living skin noninvasively. It takes advantage of the short temporal coherence of a broad-band light source to reject scattered light. Because this microscope is still in an early stage of development, its potential as a diagnostic tool in dermatology has not yet been determined. OBJECTIVE: This study was designed to explore potential applications of optical coherence microscopy in dermatology. The aim was to investigate the structures in skin that can be seen without staining or using sophisticated image-processing methods. METHODS: A prototype fiberoptic microscope was assembled that uses a 1,300-nm light-emitting diode as a light source. Scans were obtained from the skin on the index finger and forearm. Subsurface structures were identified based on knowledge of the anatomy of normal healthy skin. RESULTS: Structures located as deep as 1 mm below the surface of the skin could be imaged with a resolution of about 10 microns in the axial and lateral dimensions. In optical slices taken perpendicular to the skin surface, the contours of the epidermal ridges and the boundary between the epidermis and dermis were readily observed. CONCLUSIONS: The results of this study suggest that an optical coherence microscope may have value as a diagnostic tool for cases in which visualization of subcellular details is not required. The resolution, contrast and scanning speed of the microscope need to be improved. PMID- 8520075 TI - Effect of donor age on response of skin grafts to gamma-interferon. AB - BACKGROUND: Failure of aged human epidermis to induce HLA-DR antigens after intradermal administration of gamma-interferon (IFN-gamma) has recently been observed. OBJECTIVE: The purpose of the study was to find out whether this observation reflects an intrinsic impairment in the aged skin or is rather due to an environmental factor. METHODS: Aged and young human skin grafted onto nude mice were injected with IFN-gamma, and the induction of HLA-DR, intercellular adhesion molecule-1 (ICAM-1) and Langerhans cell (LC) migration patterns were studied. RESULTS: Increased surface expression of both HLA-DR and ICAM-1 molecules by epidermal cells was observed in all grafts, after IFN-gamma injections, whereas a decrease in LC was found only in the young grafts. CONCLUSION: This study may indicate that the lack of response of aged skin to IFN gamma is due to both intrinsic impairment in epidermal cell function and changes in function of cells outside the epidermis such as lymphocytes and endothelial cells. PMID- 8520076 TI - Water handling in patients receiving haloperidol decanoate. AB - OBJECTIVE: To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. DESIGN: Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. SETTING: A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. PARTICIPANTS: Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. MAIN OUTCOMES MEASURES: Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. RESULTS: Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). CONCLUSIONS: Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD. PMID- 8520077 TI - Estimating phenytoin concentrations by the Sheiner-Tozer method in adults with pronounced hypoalbuminemia. AB - OBJECTIVE: To assess the performance of the Sheiner-Tozer equation when used to evaluate total phenytoin concentrations in patients with pronounced hypoalbuminemia. DESIGN: Patients with phenytoin concentrations drawn at least 5 days after initiation of therapy and with serum albumin concentrations of less than 25 g/L were identified during routine daily monitoring. Phenytoin samples were frozen at -30 degrees C, batched, and later thawed for total and free phenytoin assay. Separation of free phenytoin concentration was performed at 37 degrees C using a Centrifree micropartition filter. SETTING: A 400-bed university teaching hospital. PATIENTS: Twenty-nine adults with hypoalbuminemia receiving phenytoin therapy. Patients receiving drugs known to displace phenytoin, or those with renal failure, abnormal liver enzymes, or increased bilirubin concentrations were excluded. MAIN OUTCOME MEASURE: Precision and bias of the normalized result using the Sheiner-Tozer equation were assessed with respect to observed phenytoin concentrations. RESULTS: The Sheiner-Tozer equation underpredicts the measured free concentration by approximately 12.4%. The equation provides a small but statistically significant bias (-2.7 mg/L) and a root mean squared error significantly different from 0. For most of our patients these departures appear small enough to warrant an initial empiric appraisal of hypoalbuminemia using the Sheiner-Tozer method. CONCLUSIONS: The Sheiner-Tozer equation can normalize total phenytoin concentrations reliably in patients with low albumin concentrations at our institution. PMID- 8520078 TI - Disease-based assessment of peripheral vascular disease in nursing facility patients. AB - OBJECTIVE: To determine the frequency of diagnosis of peripheral vascular disease (PVD) and selected related conditions in patients in a nursing facility, to determine the frequency of patients with risk factor(s) for or clinical evidence of PVD but without a diagnosis of PVD or a related condition, and to determine the frequency with which patients with and without a diagnosis of PVD or a related condition were treated with drug and nondrug therapies. DESIGN: A multicenter, disease-based, retrospective evaluation. SETTING: 41 nursing facilities in 6 regions of the US. PATIENTS: 4038 patients in a nursing facility: 827 patients with a PVD or related diagnosis; 2719 patients without a PVD or related diagnosis but with risk factor(s) for or clinical evidence of PVD; and 492 patients without a PVD or related diagnosis, risk factor(s), and clinical evidence. MAIN OUTCOME MEASURES: Evidence of disease and drug therapy for PVD. RESULTS: PVD was documented in 21% of patients; another 67% had risk factor(s) for or clinical evidence of PVD but no diagnosis of PVD or a related condition. Pentoxifylline was prescribed for 3% of the total sample and 12% of patients with PVD or a related condition. CONCLUSIONS: PVD appears to be inadequately evaluated in patients in a nursing facility. Disease treatment strategies should be developed and implemented to educate healthcare professionals and the general public about the need to acknowledge, assess, and treat PVD and related conditions. PMID- 8520080 TI - Quality assessment of economic evaluations in selected pharmacy, medical, and health economics journals. AB - OBJECTIVE: To assess and compare the quality of economic studies in selected pharmacy, medical, and health economics journals. DATA SOURCES: DICP The Annals of Pharmacotherapy, American Journal of Hospital Pharmacy, Hospital Pharmacy, New England Journal of Medicine, Medical Care, Journal of the American Medical Association, PharmacoEconomics, International Journal of Technology Assessment in Health Care, and Journal of Health Economics using MEDLINE, EMBASE, and International Pharmaceutical Abstracts. Search terms included "economic," "cost," and "cost analysis." STUDY SELECTION: Reviewers appraised abstracts to identify original research published during 1989-1993 comparing costs and outcomes between drugs, treatments, and/or services. Initially, 123 articles met criteria; 16 were inappropriate, 17 were randomized out, and 90 (73%) were used (30/group). DATA EXTRACTION: Quality was assessed using a 13-item checklist. Interrater reliability was 0.91 (p < 0.05) for 9 raters, test-retest reliability was 0.94 (p < 0.001). DATA SYNTHESIS: A 2-way ANOVA, with overall quality scores as a dependent variable with journal type and year as independent variables, was significant (F = 2.79, p = 0.002, r2 = 0.34), with no significant interaction (F = 0.71, p = 0.68) or time effect (F = 0.70, p = 0.60). Journal types differed; pharmacy journals scored significantly lower (chi 2 = 53.89, df = 2, p < 0.001). Items rated adequate (i.e., correct or acceptable) increased over time (chi 2 = 21.18, df = 4, p < 0.001). Ethical issues and study perspective most needed improvement. CONCLUSIONS: Article quality for all journal types increased over time nonsignificantly; health economics journals scored highest, then medical journals, with pharmacy journals significantly lower (and having the highest standard deviation). We recommend that authors and reviewers pay closer attention to study perspective and ethical implications. PMID- 8520079 TI - Impact of preexisting health conditions on the outcome of an adverse drug reaction alerting program: gastrointestinal disorders before piroxicam and sulindac therapy. AB - OBJECTIVE: To assess the impact of data concerning preexisting serious gastrointestinal (GI) disorders before piroxicam and sulindac therapy in an acute adverse drug reaction alerting program. DESIGN: Cohort study. SETTING: Saskatchewan province's prescription drug and healthcare insurance system covering a population of approximately 1 million. PARTICIPANTS: The first 20,000 new patients who were dispensed piroxicam in 1982 and the first 20,000 patients who were dispensed sulindac in 1979-1981 through the Saskatchewan drug plan. MAIN OUTCOME MEASURES: Physician services and hospitalizations with a diagnosis of peptic ulceration or GI hemorrhage within 30 days of the first piroxicam or sulindac prescription. RESULTS: Rates of physician services for peptic ulceration or GI hemorrhage in the 30 days after starting piroxicam or sulindac therapy for patients who had services or hospitalizations for serious stomach or duodenum disorders in the 90 days before their prescriptions were significantly greater than the corresponding rates for patients without a recent history of these conditions (piroxicam: odds ratio [OR] = 7.89; 95% confidence interval [CI] = 5.71 to 10.91; p < 0.001; sulindac: OR = 24.08; 95% CI = 18.99 to 30.54; p < 0.001). Also, the rate of hospitalizations for peptic ulceration or GI hemorrhage in the 30 days after starting sulindac therapy for patients who had services for the conditions in the previous 90 days was significantly greater than the rate for patients who did not (OR = 10.91; 95% CI = 5.70 to 20.87; p < 0.001). CONCLUSIONS: Rates of serious GI disorders in patients taking piroxicam and sulindac with a recent history of such disorders were larger than those in the other patients. However, because the proportion of individuals with recent serious GI disorders is small, these differences are lost in an overall assessment of patients taking these drugs. Data regarding preexisting health conditions are essential in adverse drug reaction alerting program and, indeed, in all evaluations of adverse reactions. PMID- 8520081 TI - Use of haloperidol infusions to control delirium in critically ill adults. AB - OBJECTIVE: To describe and discuss the use of continuous intravenous infusions of haloperidol to treat severe delirium and agitation in 3 intensive care unit (ICU) patients. CASE SUMMARIES: Three severely agitated patients in ICU did not respond to conventional therapy with opiates, benzodiazepines, and intermittent intravenous doses of haloperidol. In each case, control was achieved rapidly after initiation and titration of a continuous haloperidol infusion. Two patients had a history of schizophrenia. No adverse effects attributable to therapy were identified. DISCUSSION: Haloperidol is often used in the ICU for control of severe agitation, even in patients without a psychiatric history. It usually is given by bolus intravenous injection, sometimes in high doses (> 5 mg), even though that is not approved by the Food and Drug Administration. Intravenous haloperidol is generally well tolerated, but multiform ventricular tachycardia has been reported. Experience with continuous haloperidol infusions is growing, and it appears to be an effective method for control of severe agitation or delirium. In our experience and in other limited published data, adverse effects are rare, but prolongation of the QT interval has occurred and multiform ventricular tachycardia is likely a risk. CONCLUSIONS: In selected patients, a continuous infusion of haloperidol may be a useful alternative for control of agitation and delirium. Close monitoring for QT prolongation or rhythm disturbances is mandatory. PMID- 8520082 TI - Recurrent methicillin-resistant Staphylococcus aureus osteomyelitis: combination antibiotic therapy with evaluation by serum bactericidal titers. AB - OBJECTIVE: To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy. CASE SUMMARY: Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred. DISCUSSION: Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing. CONCLUSIONS: Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA. PMID- 8520083 TI - Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly. AB - OBJECTIVE: To report 3 cases of gastrointestinal (GI) complications associated with the use of intramuscular ketorolac tromethamine therapy in elderly patients. CASE SUMMARIES: In case 1, an 88-year-old woman was taken to surgery for the management of an acute abdomen and repair of a 2+ cm perforated prepyloric gastric ulcer. The patient had received a total 16 doses of ketorolac 30 mg im. The patient died after surgery from complications associated with bacterial and candidal sepsis, as well as acute renal failure. In case 2, an 80-year-old woman with no known history of GI problems developed a prepyloric gastric ulcer, which perforated and penetrated into the pancreas after the patient received 13 doses of ketorolac 30 mg im. The patient died from complications associated with candidal sepsis, peritonitis, and cardiopulmonary collapse. In case 3, an 85-year old man with a history of a gastric ulcer developed GI bleeding after receiving a total of 9 doses of ketorolac 30 mg im. The bleeding was stabilized and the patient was discharged 12 days later in stable condition. DISCUSSION: Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug with potent analgesic properties. We report 3 cases of GI complications associated with intramuscular ketorolac therapy in the elderly. A temporal relationship was established with the development of gastric ulceration in 2 patients and the recurrence of a gastric ulcer in the third patient. CONCLUSIONS: We recommend that the manufacturer's guidelines be followed when ketorolac is used in elderly patients, and the drug should not be used in patients with a history of gastric ulcer disease. The use of misoprostol may be warranted as prophylactic therapy in high risk patients who are receiving ketorolac. PMID- 8520084 TI - Hydrochlorothiazide-induced acute pulmonary edema. AB - OBJECTIVE: To describe a patient with noncardiogenic acute pulmonary edema induced by hydrochlorothiazide. CASE SUMMARY: A 70-year-old woman in generally good health, except for mild pedal edema, developed acute pulmonary edema after ingesting hydrochlorothiazide 12.5 mg for the first time. DISCUSSION: This is the fifteenth reported case of noncardiogenic pulmonary edema induced by hydrochlorothiazide. The investigations by previous authors seemed to rule out an immunologic mechanism; thus, the pathogenesis of the reaction is unknown. Most of the reactions have occurred in women. CONCLUSIONS: Noncardiogenic pulmonary edema appears to be an idiosyncratic reaction that occurs with some specificity with the thiazide diuretics. Clinicians should be aware of this potential, serious adverse reaction that occurs without warning. PMID- 8520085 TI - Tobramycin-induced hypersensitivity reaction. AB - OBJECTIVE: To report a case of a hypersensitivity reaction associated with the use of intravenous tobramycin in a patient with cystic fibrosis. CASE SUMMARY: An 18-year-old man was hospitalized for exacerbation of his cystic fibrosis. Tobramycin 125 mg iv q6h and ceftazidime 2 g iv q8h were administered through the patient's implantable access system in the left chest. Within seconds of receiving the third dose of tobramycin, the patient experienced shaking, his left arm turned white, and urticaria and pruritus were noted on the left side of the patient's chest. The patient had experienced a similar incident, accompanied by breathing difficulty, with intravenous tobramycin 4 years prior to this incident. The patient had been skin-tested for tobramycin allergy and had been desensitized and was receiving tobramycin since that time without incident. The patient's desensitization was maintained with tobramycin 160 mg/d hs by nebulization, but the drug had been discontinued by the patient 6 months prior to the latest event. DISCUSSION: Hypersensitivity reactions to aminoglycosides are unusual. Hypersensitivity to 1 aminoglycoside antibiotic frequently is associated with hypersensitivity to at least 1 other amino-glycoside. In patients who develop hypersensitivity to an amino-glycoside antibiotic, desensitization may be an effective alternative to changing therapy. CONCLUSIONS: Tobramycin is very important in the drug regimen for Pseudomonas aeruginosa infections in patients with cystic fibrosis. Effective desensitization can be maintained by daily administration of nebulized tobramycin. PMID- 8520086 TI - Dissolution of phenytoin precipitate with sodium bicarbonate in an occluded central venous access device. AB - OBJECTIVE: To report a case of restored patency of a central venous access device occluded by precipitate of phenytoin sodium injection. CASE SUMMARY: A patient experienced total occlusion of an implanted subcutaneous port caused by precipitation of phenytoin. Phenytoin sodium injection was mixed inadvertently with dextrose 5% in NaCl 0.45% injection during intravenous administration. Dextrose 5% in NaCl 0.45% injection, which is acidic (pH 4.0), caused the phenytoin sodium injection, a basic solution (pH 12.0), to precipitate. Local instillation of sodium bicarbonate 8.4% injection to decrease the pH of the medium restored patency of the occluded port. DISCUSSION: There are reports of local instillation of solvent restoring central ports occluded by lipid containing parenteral nutrient admixture, calcium phosphate salt precipitate, and coagulated blood. No report of local instillation into an occluded port to dissolve precipitate of phenytoin could be found. Several factors are involved in the precipitation and dissolution of phenytoin. The key factor in this case was the hydrogen ion concentration (pH) of the solution. Decreased pH caused the precipitation, but increased pH caused the dissolution of the precipitate of phenytoin. CONCLUSIONS: Sodium bicarbonate injection was a suitable agent for clearing precipitate of phenytoin in this case of an occluded implanted central venous access device. PMID- 8520087 TI - Continuous subcutaneous heparin infusion for treatment of Trousseau's syndrome. AB - OBJECTIVE: To describe the use of continuous subcutaneous heparin infusion in the treatment of 2 cases of Trousseau's syndrome. CASE SUMMARIES: Two patients with metastatic carcinoma presented to the hospital with acute coagulopathies consistent with a diagnosis of Trousseau's syndrome. In both cases conventional anticoagulant therapies proved to be impractical and ineffective. DISCUSSION: Considerable literature suggests that oral anticoagulants such as warfarin are ineffective in the treatment of Trousseau's syndrome. Heparin is more effective for this purpose, although continuous intravenous infusion may prove difficult in the ambulatory setting. Intermittent subcutaneous injections of heparin or low molecular-weight heparin may not provide reliable anticoagulation for the entire dosage interval. Although the use of continuous subcutaneous infusion of heparin has been used for anticoagulation during pregnancy, this is the first report of the use of sodium heparin administered by continuous subcutaneous infusion in the treatment of Trousseau's syndrome. CONCLUSIONS: Continuous subcutaneous heparin infusion may be an effective option for the treatment of Trousseau's syndrome in the ambulatory setting. PMID- 8520088 TI - Diclofenac-associated thrombocytopenia and neutropenia. AB - OBJECTIVE: To report a case of thrombocytopenia and a case of neutropenia, both associated with the use of diclofenac. CASE SUMMARIES: A 63-year-old woman was receiving diclofenac for osteoarthritis. During a hospital admission for pneumonia, she was found to have severe thrombocytopenia. Diclofenac therapy was stopped and the thrombocytopenia resolved. Several months later she was inadvertently treated with diclofenac by another physician and again experienced thrombocytopenia, which again resolved on discontinuation of the drug and has not recurred since. A 72-year-old man was receiving diclofenac for 9 months for osteoarthritis. He was then found to have asymptomatic neutropenia. Diclofenac therapy was stopped and the neutropenia resolved with no other intervention. He was not rechallenged. DISCUSSION: Severe thrombocytopenia and neutropenia are extremely rare adverse reactions to diclofenac. To date, there is only 1 case of each that is well documented and supported in the literature. CONCLUSIONS: Severe thrombocytopenia and neutropenia are potential serious adverse effects of the use of diclofenac. Patients who are receiving diclofenac and develop symptoms of either thrombocytopenia or neutropenia should have a complete blood count, and if this diagnosis is confirmed, the drug therapy should be stopped. PMID- 8520089 TI - Recent advances: ambulatory care and family medicine. AB - Recent advances in primary care have been and continue to be exciting and innovative. The evolution of pharmaceutical care has the potential to have an immediate impact in the primary care arena. A major focus of primary care research will center on the evaluation of pharmaceutical care and the consequences of implementing pharmaceutical care, such as reimbursement for clinical services, quality of life, and improved clinical outcomes. With an increasing emphasis being placed on the provision of health care through primary care providers, advances in primary care/family medicine pharmacotherapy promise to remain exciting and innovative. PMID- 8520090 TI - Use of confidence intervals and sample size calculations in health economic studies. AB - OBJECTIVE: To discuss the calculation and application of confidence intervals in pharmacoeconomic studies. DATA SYNTHESIS: The increasing frequency with which pharmacoeconomic evaluations are made within clinical trials makes it possible to obtain information on the outputs and costs of an intervention in each patient of a sample under study. This allows the same statistical principles commonly used in clinical trials to be applied to cost or cost-effectiveness data. The methodology described in this article would allow expression of cost effectiveness ratios in the form of confidence intervals. The calculation of the cost-effectiveness ratio by means of a confidence interval may have important practical consequences, both in decision-making on the choice of 1 intervention versus another and in calculating the size of the sample necessary to identify statistically significant differences, from both clinical and economic points of view. CONCLUSIONS: The complementary use of confidence intervals and sensitivity analysis makes it possible to measure uncertainty related and unrelated to variability in sample data, allowing the decision to adopt 1 technology or another to be based on the most objective information available. Although several ethical and methodologic concerns remain to be addressed, this methodology may contribute to improving the more rational and efficient use of drugs. PMID- 8520091 TI - Phenytoin-folic acid interaction. AB - OBJECTIVE: To review information regarding the dual and interdependent drug nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid. DATA SOURCES: Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references. STUDY SELECTION: All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction. DATA EXTRACTION: Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events. DATA SYNTHESIS: Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the "pseudo-steady state," which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner. CONCLUSIONS: Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics. PMID- 8520092 TI - Desogestrel, norgestimate, and gestodene: the newer progestins. AB - OBJECTIVE: To review and compare the newer progestins desogestrel, norgestimate, and gestodene with regard to chemistry, pharmacokinetics, efficacy, and tolerability. DATA SOURCES: Primary literature on desogestrel, norgestimate, and gestodene was identified from a comprehensive MEDLINE English-literature search from 1984 through 1994, with additional studies selected by review of the references. Indexing terms included progestins, desogestrel, gestodene, norgestimate, levonorgestrel, and norgestrel. STUDY SELECTION: Only human clinical and pharmacokinetic trials performed in Europe, Canada, and the US were included. DATA EXTRACTION: All available data from human studies were reviewed; both comparative and noncomparative studies were included because of the paucity of direct comparative information available. DATA SYNTHESIS: The newer progestins were designed to minimize the adverse effects (e.g., acne, hirsuitism, nausea, carbohydrate and lipid metabolism changes) observed with older oral contraceptives (OCs) while maintaining efficacy and good menstrual cycle control. Desogestrel, norgestimate, and gestodene have minimal amounts of androgenicity and antiestrogenic potential. All of these agents are pharmacokinetically similar to older agents: they are highly bioavailable when administered orally, hepatically metabolized, and obtain steady-state concentrations after 8-10 days of continuous administration. The newer agents have similar Pearl Indexes and slightly better cycle control. Furthermore, the new progestins appear to cause fewer adverse effects, such as acne and hirsuitism, and similar rates of weight gain, blood pressure changes, and lipid and carbohydrate metabolism changes. CONCLUSIONS: Desogestrel, norgestimate, and gestodene appear to offer clinical advantages because of their decreased androgenicity. Women whose cycles are currently well controlled with other OCs should not be switched to a newer progestin. However, any of the combination OC products that contain these progestins may be prescribed for women intolerant of older agents or to first time users of OCs. The newer progestins appear to be efficacious and offer similar cycle control, improved safety and tolerability profiles, and comparable price with the older agents. PMID- 8520093 TI - Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. AB - OBJECTIVE: To evaluate the comparative efficacy and safety of the 4 currently available hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, fluvastatin, lovastatin, pravastatin, and simvastatin, in the treatment of primary hypercholesterolemia. DATA SOURCES: English-language clinical studies, abstracts, and review articles identified from MEDLINE searches and bibliographies of identified articles. Unpublished data were obtained from the Food and Drug Administration in accordance with the Freedom of Information Act. STUDY SELECTION: Placebo-controlled and comparative studies of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. DATA EXTRACTION: Pertinent studies were selected and the data were synthesized into a review format. DATA SYNTHESIS: The chemistry, pharmacology, and pharmacokinetics of the 4 HMG-CoA reductase inhibitors are reviewed. Clinical trials evaluating the hypocholesterolemic efficacy of the HMG-CoA reductase inhibitors are examined, and results on the comparative efficacy and safety of these agents are summarized. On a milligram-per-milligram basis, simvastatin is twice as potent as lovastatin and pravastatin. The hypocholesterolemic effects of fluvastatin appear to be approximately 30% less than that of lovastatin. In posttransplant patients receiving cyclosporine, safety has been documented for low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA reductase inhibitor is warranted, pravastatin should be considered the drug of choice because of a lower incidence of myopathy. Relevant data on the incidence of adverse effects are presented. Pertinent outcomes data from clinical trials evaluating the effect of HMG-CoA reductase inhibitors on atherosclerosis regression and coronary mortality, as well as published economic analyses of cholesterol-lowering agents, are summarized. Recommendations on the selection of an HMG-CoA reductase inhibitor in various clinical situations are provided. CONCLUSIONS: The literature supports the comparable safety and tolerability of all 4 currently available HMG-CoA reductase inhibitors. Therefore, the choice of an HMG-CoA reductase inhibitor should depend on the extent of cholesterol lowering needed to meet the recommended treatment goal established by the National Cholesterol Education Program. Direct comparative studies are needed to confirm the relative, long-term cost-effectiveness of the various HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia. PMID- 8520094 TI - Therapeutic approaches for AIDS-related toxoplasmosis. AB - OBJECTIVE: To summarize current knowledge of prophylaxis and treatment of AIDS related toxoplasmosis. DATA SOURCES: A MEDLINE search (1985-1994) was used to identify pertinent literature, including reviews. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: Trimethoprim/sulfamethoxazole (TMP/SMX) appears to be useful for prophylaxis against toxoplasmosis in patients with AIDS. The most effective TMP/SMX dose for prevention of toxoplasmosis needs to be determined. Dapsone in combination with pyrimethamine therapy may be an effective alternative for toxoplasmosis prophylaxis. The most effective regimen for the treatment of AIDS related toxoplasmosis is the combination therapy of pyrimethamine/sulfadiazine. In patients who cannot tolerate sulfadiazine therapy because of adverse effects or allergy, pyrimethamine with clindamycin therapy may be considered as a second line alternative. Lifelong suppressive therapy is required after either treatment regimen to prevent relapse. Other newer agents such as azithromycin, clarithromycin, atovaquone, or timetrexate-leucovorin need further studies to confirm their true effectiveness in the treatment of toxoplasmosis. CONCLUSIONS: TMP/SMX remains a useful agent in prophylaxis against toxoplasmosis. Pyrimethamine/sulfadiazine is the most effective combination in the treatment of acute toxoplasmosis. PMID- 8520095 TI - Peripheral diabetic neuropathy: current concepts in treatment. AB - OBJECTIVE: To review pathophysiology and current concepts in the treatment of diabetic peripheral neuropathy (PN). DATA SOURCES: References were identified through a MEDLINE search of the English-language literature from 1976 through 1994. Additional references were obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Clinical trials that involved an adequate number of patients and review articles were selected. Information from articles that was judged by the authors to be significant was selected for discussion. DATA SYNTHESIS: PN affects 5-50% of people with diabetes in the US and most commonly is characterized by tingling or burning sensations, particularly in the calves, ankles, and feet, with a loss of vibratory sense. Treatment of PN, for the most part, has been unsatisfactory. Therapy has been directed toward either improving nerve function or alleviating symptoms of PN, including pain and paresthesia. Glycemic control may slow the progression of PN. Hyperglycemia also is associated with decreased pain threshold in patients with diabetes mellitus. The aldose reductase inhibitors, particularly tolrestat, have been shown to improve objective and subjective neurologic function. Pain or paresthesia has been treated effectively with antidepressants, lidocaine, mexiletine, and capsaicin. The anticonvulsants phenytoin and carbamazepine may be effective, but are associated with a greater degree of adverse effects. Experimental treatments, such as gamma-linolenic acid, gangliosides, uridine, and the corticotropin4-9 analog ORG 2766, have been effective in improving neurologic function. CONCLUSIONS: Treatment of PN remains unsatisfactory. Therapy should be directed toward prevention with glycemic control and symptomatic treatment of existing PN. PMID- 8520096 TI - Recombinant erythropoietin for zidovudine-induced anemia in AIDS. AB - Recombinant erythropoietin (Epogen, Amgen Pharmaceuticals; Procrit, Amgen Pharmaceuticals, distributed by Ortho Biotech) is approved for use in anemia associated with HIV infection and treatment. The recommended starting dose is 100 IU/kg iv or sc 3 times per week. Current evidence suggests that anemia in zidovudine-treated patients may be a result of insufficient quantities of erythropoietin, bone marrow unresponsiveness to the hormone, or HIV infection. Among patients receiving zidovudine, a review of the available data suggests that baseline serum erythropoietin concentrations may aid in predicting the response to exogenous hormone administration. PMID- 8520097 TI - Topical nonsteroidal antiinflammatory drugs for acute soft tissue injuries. AB - The empirical evidence supporting the use of topical NSAIDs in acute soft tissue injuries is weak. However, patient ratings of improvement consistently favor NSAID treatment over placebo. Although it is very difficult to differentiate the placebo effect from the natural course of improvement in these patients, the overall impression given by these studies is that of superior efficacy of topical NSAIDs over placebo. The study by Akermark and Forsskahl suggests that indomethacin applied topically is as effective as therapeutic doses of oral indomethacin. Further studies need to be conducted to generalize this conclusion to other NSAIDs. Studies comparing the relative efficacy of topical NSAIDs with counterirritants available over-the-counter (e.g., menthol, camphor, methylsalicylate) also would be useful. PMID- 8520098 TI - Misoprostol for tinnitus. AB - Practitioners should realize that further study of misoprostol in larger patient populations must be undertaken to determine its efficacy and safety in the treatment of tinnitus. Previous approaches to treating tinnitus have included carbamazepine, phenytoin, lidocaine, tocainide, flecainide acetate, alprazolam, and nortriptyline. Studies using lidocaine, nortriptyline, or alprazolam have shown encouraging results. The relative contribution of misoprostol remains to be seen; however, it may offer a new treatment option to patients who have experienced adverse effects or have contraindications to the pharmacologic agents currently available. PMID- 8520099 TI - Ketoconazole to prevent acute respiratory distress syndrome in critically ill patients. AB - Ketoconazole appears to be an effective prophylactic measure in surgical patients at risk of developing ARDS. The beneficial effects may be caused by thromboxane synthetase inhibition because thromboxane B2 concentrations were decreased by ketoconazole in both studies. Two studies were unable to demonstrate a beneficial effect with the selective thromboxane synthetase inhibitor dazoxiben. Both studies consisted of a small number of subjects with already established ARDS, not prophylaxis in patients at risk of ARDS. Although the effects of ketoconazole on mortality in patients at risk of ARDS are conflicting, there may be reduced mortality in patients with sepsis. Several issues must be considered before ketoconazole is used in this setting. First, the studies to date have excluded patients at risk of hepatotoxicity, which is probably wise considering the potential hepatotoxicity with ketoconazole and the unknown benefit/risk ratio in these patients. Also, therapies that reduce gastric acidity should be avoided to ensure bioavailability. If ketoconazole is administered through a jejunostomy tube, it probably should be given with a dilute acid to enhance absorption. Furthermore, ketoconazole is a known inhibitor of the cytochrome P450 system, which results in a number of drug interactions. If ketoconazole is used, the patient's current drug therapy should be reviewed for potential interacting drugs. In light of the current studies, ketoconazole may be considered for surgical patients at risk of developing ARDS (especially patients with sepsis) with the previously noted considerations. Future research should seek to confirm ketoconazole's role for the prevention of ARDS in all critically ill patients. Additional studies also should clarify the role of various inflammatory mediators in the pathophysiology and therapy of ARDS. PMID- 8520100 TI - Autoimmune hemolytic anemia induced by diclofenac. PMID- 8520101 TI - Increased theophylline clearance during hemofiltration. PMID- 8520102 TI - Hyperprolactinemia and galactorrhea with standard-dose famotidine therapy. PMID- 8520103 TI - Computer-assisted pharmacovigilance in hospitalized patients. PMID- 8520104 TI - Significance of plasma thiothixene concentrations. PMID- 8520105 TI - Antioxidative activity of tetrahydrocurcuminoids. AB - In order to develop a new type of antioxidative compound which has both the phenolic and beta-diketone moiety in the same molecule, we converted three known curcuminoids, curcumin (diferuloylmethane, U1), (4-hydroxy-3 methoxycinnamoyl)methane (U2), and bis-(4-hydroxycinnamoyl)methane (U3), which are the natural antioxidants of Curcuma longa L. (tumeric), to tetrahydrocurcuminoids (THU1, THU2, and THU3, respectively) by hydrogenation, and evaluated their antioxidative activity by using linoleic acid as the substrate in an ethanol/water system. Further, we used the rabbit erythrocyte membrane ghost and rat liver microsome as in vitro systems and determined the antioxidative activity of these curcuminoids. When we evaluated their antioxidative activity by these assays, it was found that THU1 had the strongest antioxidative activity among all curcuminoids in each assay system. THU1 has been reported to be one of the main metabolites of U1 in vivo [Holder et al., Xenobiotica, 8, 761-768 (1978)]. These results suggest that THU1 must play an important role in the antioxidative mechanism of U1 in vivo by converting U1 into THU1. PMID- 8520106 TI - Construction, purification, and properties of a truncated alkaline endoglucanase from Bacillus sp. KSM-635. AB - Part of a 2.4-kb DNA fragment that encoded the amino-terminal 584 residues (65 kDa) of an alkaline endoglucanase from Bacillus sp. KSM-635 (941 amino acid residues; 105 kDa) was spontaneously deleted during subcloning of the fragment. The remaining 1.1-kb insert of the deleted plasmid encoded amino acids from Ala228 to Leu584 of the enzyme. However, Escherichia coli HB101 cells harboring this plasmid produced an active endoglucanase. After addition of a termination codon, TAA, immediately downstream of the codon for Leu584, the 1.1-kb fragment was inserted into an expression vector, pHSP64. The resultant plasmid was introduced into Bacillus subtilis ISW1214 for extracellular production of the truncated endoglucanase. The enzyme was then purified to homogeneity from a culture of the recombinant B. subtilis cells. Amino-terminal sequencing of the enzyme showed that the enzyme consisted of 7 amino acid residues encoded by the vector and 357 amino acid residues encoded by the truncated gene, with a molecular mass of 40.2 kDa. The purified enzyme was very active against carboxymethylcellulose and its pH and temperature profiles were almost identical to those of the enzyme produced by Bacillus sp. KSM-635. PMID- 8520107 TI - Cholesteryl ester accumulation in macrophages treated with oxidized low density lipoprotein. AB - The ability of CuSO4- and hypochlorite-oxidized LDL to promote cholesterol accumulation in macrophages was examined. Both CuSO4- and hypochlorite-oxidized LDL were rapidly metabolized by mouse peritoneal macrophages to a level approximately 10 times that observed for native LDL and both modified lipoproteins increased the accumulation of unesterified cholesterol. However when each modified lipoprotein was incubated with macrophages for 40h, only hypochlorite-oxidized LDL produced significant accumulation of cholesteryl esters, with levels approaching 85 micrograms/mg cell protein. This finding was verified by nile red staining. The cholesteryl ester content of cupric sulfate modified LDL was found to be significantly decreased when compared to either native or hypochlorite-modified LDL promotes massive cholesteryl ester accumulation because the cholesteryl ester content of the LDL particle is preserved. PMID- 8520108 TI - Reinvestigation of the structure of the esterified cerebroside in the epidermis of guinea pigs. AB - One of the esterified cerebroside in the epidermis of guinea pigs is shown to be (2S,3R,4E,23'Z)-1-O-(beta-D-glucopyranosyl)-N-(32'-linoleoyloxy -23' dotriacontenoyl)-4-sphingenine by chemical and spectroscopic studies. PMID- 8520109 TI - Synthesis of the esterified cerebroside in the epidermis of guinea pigs. AB - (2S,3R,4E,23'Z)-1-O-(beta-D-Glucopyranosyl)-N-(32'-linoleoyloxy -23' dotriacontenoyl)-4-sphingenine (1), a component of the esterified cerebrosides in the epidermis of guinea pigs, was synthesized by selective N-acylation of (2S,3R,4E)-1-O-(beta-D-glucopyranosyl)-4-sphingenine (18) with activated omega linoleoyloxy fatty acid ester 17. PMID- 8520110 TI - A hyperthermophilic sulfur-reducing archaebacterium, Thermococcus sp. DT1331, isolated from a deep-sea hydrothermal vent. AB - A hyperthermophilic archaebacterium was isolated from a deep-sea black smoker chimney (depth, 760 m) at the Minami-ensei Knoll (28 degrees 23'N, 127 degrees 38'E). The strain, designated DT1331, was a coccoid shaped bacterium about 0.5 to 1.0 microns in diameter. The cells were surrounded by a cell envelope. The temperature for growth was between 55 degrees C and 93 degrees C with an optimum 80 degrees C. The growth occurred from pH 4.5 to 8.5 and the optimum pH was 6.0. DT1331 required 1% to 5% NaCl for growth and cell lysis was observed below 1% NaCl concentration. The strain was an anaerobic chemoorganotroph requiring elemental sulfur obligately. Organic substrates used included tryptone, peptone, soytone, casein, gelatin, and yeast extract. Under the optimal conditions, DT1331 had a generation time of 50 min and could reach densities of about 1.5 x 10(8) cells/ml. DT1331 was resistant to ampicillin, chloramphenicol, erythromycin, kanamycin, streptomycin, and tetracycline, which was one of the common characteristics of archaebacteria. The G+C content of DT1331 was 52.3 mol%. Analysis of the 16S rRNA gene by restriction enzymes coincided with those of Thermococcus celer, indicating that this strain belonged to the genus Thermococcus. PMID- 8520111 TI - Two-dimensional gel electrophoresis of ribosomal proteins as a novel approach to bacterial taxonomy: application to the genus Arthrobacter. AB - Ribosomal proteins from 22 strains of 15 different species belong to the genus Arthrobacter were analyzed by an improved two-dimensional gel electrophoresis. Electrophoretograms of ribosomal proteins from 15 type strains had species specific patterns. Similarity coefficients (SAB values) of ribosomal proteins with mol. wt. of greater than about 20,000, among strains of the same species (DNA relatedness values of more than 61%) were greater than 0.85, but the SAB values among strains of different species were less than 0.60. The N-terminal amino acid sequences of the AL2 proteins, which migrated into similar positions in this method, from 5 type strains were shown to be highly homologous. Our results indicated that ribosomal proteins have been conserved within species during evolution and that the members of the genus Arthrobacter are phylogenetically homogeneous. Thus, ribosomal protein profiles by this method are a potential tool for strain identification. PMID- 8520112 TI - Chromosome bisection in the yeast Saccharomyces cerevisiae facilitated by yeast artificial chromosomes bearing a site-specific recombination system. AB - A chromosome bisection method was constructed using yeast artificial chromosomes (YAC) and a GAL1-promoted site-specific recombination system. This method was applied to bisect chromosome IV into the left and right parts of the centromere region. The bisection occurred at frequencies of about 10% when the recombination site DNAs were integrated onto YAC and chromosome IV in the same direction, but were less than 10(-3) when they were in opposite directions. Reconstruction of the original chromosome IV from the bisected chromosomes was also induced by galactose at high frequencies. Loss of the left part chromosome was found at the frequencies of 0.9 x 10(-3) after hybrid cells between the chromosome-bisected strain and a normal haploid were subcultivated in a complete medium. The bisection and reconstruction of chromosome IV and deletion of the left part chromosome were demonstrated by electrophoretical karyotyping. PMID- 8520113 TI - Isolation and characterization of the IS3-like element from Thermus aquaticus. AB - We have cloned and characterized a genetic element (1187 bp) that is responsible for the induction of thermotolerance as well as ompC expression in E. coli. This element (ISLtaq1) was isolated from Thermus aquaticus. DNA and protein data bases were searched with this element (ISLtaq1), which suggested it to be very similar to IS150 belonging to the IS3 family. ORF1, found on ISLtaq1, which encodes 100 amino acids (aa), had a DNA-binding motif: a helix-turn-helix and a leucine zipper. In fact, when the ORF1 protein was overproduced in E. coli, thermotolerance as well as ompC expression was induced. PMID- 8520114 TI - Production of biologically active mature brain-derived neurotrophic factor in Escherichia coli. AB - A gene coding for a brain-derived neurotrophic factor (BDNF) obtained from rat BDNF cDNA was used to construct an expression plasmid, pTRSBDNF. It contained a BDNF gene that was fused, in frame, to a region encoding the beta-lactamase signal peptide. The E. coli HB101 harboring pTRSBDNF produced 18 mg/liter of mature protein. The E. coli cells produced a larger amount of BDNF than that of human nerve growth factor (hNGF), which was produced using the same expression system. The E. coli cells harboring pTRSBDNF were sonicated and centrifuged to obtain a supernatant and precipitate. The BDNF purified from the supernatant containing 20% of the total BDNF had high biological activity (EC50 of 30 pg/ml) against neurons of chick dorsal root ganglia. On the other hand, the BDNF purified from the precipitate had low biological activity (EC50 of 2 ng/ml) and incorrect disulfide bonds. PMID- 8520115 TI - Synthesis of 2-deoxy-glucooligosaccharides through condensation of 2-deoxy-D glucose by glucoamylase and alpha-glucosidase. AB - Glucoamylases from Aspergillus niger and Rhizopus niveus catalyzed condensation of 2-deoxy-D-glucose (dGlc) to yield deoxy-glucooligosaccharides with polymerization degrees of 2-5. The enzymes also gave a small amount of products from 3-deoxy-D-glucose, but no products from 6-deoxy-D-glucose. A. niger alpha glucosidase also catalyzed condensation of dGlc, while Torula and Saccharomyces alpha-glucosidases had low activity. alpha-1,4-, 1,6-, and 1,3-linked deoxy glucobioses were isolated and identified as the products of A. niger glucoamylase and A. niger alpha-glucosidase. In the reaction of the glucoamylase, 1,4- and 1,3 linked saccharides decreased with an increase of 1,6-linked one. A. niger alpha glucosidase produced alpha-1,6-linked disaccharide predominantly during the whole course of the reaction. PMID- 8520116 TI - Direct enantiomeric separation of platelet-activating factor receptor antagonist SM-10661 by ligand-exchange high-performance liquid chromatography with a copper (II) N,S-dioctyl-D-penicillamine complex. AB - The enantiomeric separation of SM-10661, a platelet activating factor receptor antagonist, was investigated by HPLC using ligand-exchange chiral stationary phases. The stereoisomers of SM-10661 could all be separated by ligand-exchange HPLC with a Cu(II) N,S-dioctyl-D-penicillamine complex (Sumichiral OA-5000). The mechanism for the resolution includes the involvement of hydrophobic interactions between SM-10661 and Cu(II) D-penicillamine. PMID- 8520117 TI - Purification and properties of endo-beta-1,4-D-galactanase from Aspergillus niger. AB - An endo-beta-1,4-D-galactanase was purified 1735-fold from a commercial enzyme preparation of Aspergillus niger. The endogalactanase was homogeneous by SDS PAGE, having an apparent molecular weight of 32,000. It specifically hydrolyzed beta-1,4-D-galactan, and is shown to be capable of releasing galactosyl oligomers and galactose from the soybean pectic polysaccharides. PMID- 8520118 TI - Characterization of rat N-acetylglucosaminyltransferase I expressed in Escherichia coli. AB - The catalytic domain (sGnT-I) of rat liver N-acetylglucosaminyl-transferase I (GnT-I) was expressed in Escherichia coli. Lysates from pETsGnT-I transformants contained a prominent protein species of 46 kDa with which a significant GnT-I activity was associated. To purify the relevant enzyme, we constructed cDNAs encoding sGnT-ICH and sGnT-INH, which had six additional histidine residues as an affinity tag at the C-terminal and the N-terminal of sGnT-I, respectively, and introduced them into E. coli cells for expression. sGnT-INH was purified and its enzymatic properties were examined. PMID- 8520119 TI - Molecular cloning of cDNA for a 17.5-kDa polypeptide, the psaL gene product, associated with cucumber Photosystem I. AB - Three cDNA clones encoding the 17.5-kDa polypeptide of cucumber Photosystem I were isolated and sequenced. A cDNA insert of them was 812 bp long and contained a long open reading frame that encoded a polypeptide with 217 amino acid residues. The deduced amino acid sequence of the cDNA was 77% and 71% identical to the amino acid sequences of psaL gene products from barley and spinach, respectively. PMID- 8520120 TI - Purification and characterization of (S)-1,3-butanediol dehydrogenase from Candida parapsilosis. AB - (S)-1,3-Butanediol (BDO) oxidizing enzyme was purified from Candida parapsilosis IFO 1396, which could produce (R)-1,3-BDO from the racemate. The purified enzyme was an NAD(+)-dependent secondary alcohol dehydrogenase that oxidized (S)-1,3-BDO to 4-hydroxy-2-butanone stereo-specifically. PMID- 8520121 TI - Purification and characterization of a new lipase from Fusarium sp. YM-30. AB - The extracellular lipase from Fusarium sp. YM-30 was purified by a procedure involving ultrafiltration, ammonium sulfate precipitation, and DEAE-Toyopearl 650M, CM-Toyopearl 650M, and Butyl-Toyopearl 650M column chromatographies. The purified lipase was homogeneous with 12kDa of molecular mass by SDS-PAGE, and had high specificities for mono- and diacylglycerols, but low toward triacylglycerols. The enzyme had maximum activity at pH 7.0 to 8.0 and 37 degrees C, and hydrolyzed digalactosyl diglyceride too. PMID- 8520122 TI - Substitution of lysine for arginine in the N-terminal 217th amino acid residue of the H gamma II of Staphylococcal gamma-hemolysin lowers the activity of the toxin. AB - The staphylococcal toxin gamma-hemolysin consists of two protein components, LukF and H gamma II. Staphylococcus aureus P83 was found to have five components, LukF, LukF-PV, LukM, LukS, and H gamma II for leukocidin or gamma-hemolysin. H gamma II of S. aureus P83 was demonstrated to be a naturally-occurring analogous molecule of H gamma II [H gamma II(P83)], in which the 217th arginine residue was replaced by lysine. The H gamma II(P83) showed about 50% of the hemolytic activity of normal H gamma II in the presence of LukF. PMID- 8520123 TI - Synthesis and mitogenic activity of nonreducing-sugar subunit analogs of bacterial lipid A composed only of 3-hydroxytetradecanoic acid and its homologs. AB - Novel analogs of the nonreducing-sugar subunit of bacterial lipid A, which were composed only of 3-hydroxytetradecanoic acid and its homologs, were synthesized. These analogs exhibited significant mitogenic activity. PMID- 8520124 TI - Evidence for the occurrence of multiple aspartic proteinases in rice seeds. AB - Using reverse transcription polymerase chain reaction (RT-PCR), we identified two cDNA fragments encoding aspartic proteinases (APs). The encoded proteins, pL4 and pL5, are similar in sequence to other plant APs including barley AP and cardoon flower AP (cyprosin). The identity was 58-76% with one another. Genomic Southern blot analysis suggested that the rice AP gene constitutes a multigene family. PMID- 8520125 TI - The nitrate reductase gene from a shoyu koji mold, Aspergillus oryzae KBN616. AB - A niaD gene encoding nitrate reductase was isolated from Aspergillus oryzae KBN616 and sequenced. The structural gene comprises 2973 bp and 868 amino acids, which showed a high degree of similarity to nitrate reductases from other filamentous fungi. The coding sequence is interrupted by six introns varying in size from 48 to 98 bp. The intron positions are all conserved among the niaD genes from A. oryzae, Aspergillus nidulans, and Aspergillus niger. A homologous transformation system was developed for an industrial shoyu koji mold, A. oryzae KBN616, based on the nitrate reductase (niaD) of the nitrate assimilation pathway. PMID- 8520126 TI - Fusarium mycotoxins (fumonisins, nivalenol, and zearalenone) and aflatoxins in corn from Southeast Asia. AB - Corn samples collected from the Philippines, Thailand, and Indonesia were surveyed for the natural occurrence of Fusarium mycotoxins (fumonisins, trichothecenes, and zearalenone) and aflatoxins. Fumonisins B1 and B2 were found in over 50% of corn samples in individual countries, and their co-occurrences with aflatoxins at the incidence of 48% were noted. In addition to these mycotoxins, a trichothecene, nivalenol, and an estrogen, zearalenone, both mycotoxins of Fusarium species, were detected in these Southeast Asian samples. This is the first report on the simultaneous occurrence of two carcinogenic mycotoxins, fumonisins and aflatoxins, together with Fusarium mycotoxins (nivalenol and zearlenone) in corn from Asian tropics. PMID- 8520127 TI - Bendectin/diclectin for morning sickness: a Canadian follow-up of an American tragedy. PMID- 8520128 TI - Effects of acetaminophen and hydroxyurea on spermatogenesis and sperm chromatin structure in laboratory mice. AB - High doses of acetaminophen (400 mg/kg) or hydroxyurea (200 mg/kg) given intraperitoneally daily for 5 d caused reduction in relative testicular weight in mice (B6C3/F1/BOM M). Testicular atrophy of several tubules was seen in the hydroxyurea-treated mice 5 d after the last exposure, whereas acetaminophen did not lead to such changes. Exposure to acetaminophen caused neither a depletion of glutathione in the testis nor a marked increase in covalent binding. In contrast, significant decreases in the incorporation of thymidine into the testis were observed during the first 3 h following a single treatment with acetaminophen (100 to 400 mg/kg) or hydroxyurea (100 to 200 mg/kg). In mice treated with acetaminophen (400 mg/kg) or hydroxyurea (200 mg/kg) daily for 5 d, flow cytometric analysis revealed large reductions in one of the tetraploid populations of testicular cells (mostly early pachytene spermatocytes) on days 5 and 10. Changes in the populations of the various spermatid stages occurred later; thus, both compounds appeared to cause a delay in spermiogenesis. Indications of abnormal chromatin structure were seen in an increased frequency of vas deferens sperm on days 27 and 33 after the last exposure, when measured as increased susceptibility towards DNA denaturation in situ. In conclusion, high doses of acetaminophen or hydroxyurea inhibit DNA synthesis in the testis. The present data indicate that this leads to reduced testicular weight, a reduction in the number of early pachytene spermatocytes, changes in the proportions of the various spermatid stages, and an apparent alteration in sperm chromatin structure. PMID- 8520129 TI - Lack of correlation between cadmium in seminal plasma and fertility status of nonexposed individuals and two cadmium-exposed patients. AB - Cadmium concentrations were determined in semen samples of 12 men with proven fertility (group I) and 44 normozoospermic patients (group II) as well as 118 unselected patients of an infertility clinic (group III) and 2 industrial workers with occupational exposure to cadmium. Mean cadmium concentrations in seminal plasma for groups I, II, and III did not show significant differences: 0.38 +/- 0.64; 0.43 +/- 0.69; 0.44 +/- 0.73 (mean +/- SD, micrograms/L), but the two cadmium-exposed patients revealed exceptionally high cadmium levels: 3.46 micrograms/L and 2.99 micrograms/L, respectively. There was no significant correlation between seminal cadmium concentrations and conventional semen parameters or between cadmium concentration and the fertility status of the patients. However, mean cadmium concentrations in seminal plasma of normozoospermic patients were higher in the group of smokers (0.55 +/- 0.81 micrograms/L), compared with the group of nonsmokers (0.42 +/- 0.67 micrograms/L), and there was a weak correlation between cadmium concentration and number of cigarettes consumed per day. PMID- 8520130 TI - Cadmium and glutathione: effect on human placental thromboxane and prostacyclin production. AB - Cadmium toxicity, noted in rodents during late gestation, has been compared with preeclampsia, a condition associated with an imbalance between thromboxane A2 and prostacyclin. This study examines the effect of cadmium on the human placental production of thromboxane A2 and prostacyclin, as reflected by their hydrolysis products (TxB2, 6-keto-PGF1 alpha). Following two 12-h exposures, 6-keto-PGF1 alpha production by placental explants was 74.8 and 39.9% of unexposed tissue values at 40 and 100 microM cadmium, respectively, with no significant effect on TxB2. The effect of glutathione on placental TxB2 and 6-keto-PGF1 alpha production was also examined. Sulfhydryl concentrations have been shown to affect thromboxane and prostacyclin production, and glutathione binds to cadmium reducing its toxicity. Although glutathione at concentrations up to 1 mM had no effect on explant function, glutathione did prevent the effects of cadmium on 6 keto-PGF1 alpha. This study indicates that acute exposure to cadmium at high concentrations directly affects the placental production of 6-keto-PGF1 alpha, disturbing the thromboxane A2/prostacyclin ratio. PMID- 8520131 TI - Effect of papain on different phases of prenatal ontogenesis in rats. AB - The present investigations were performed to re-examine the findings of previous studies conducted in the sixties and seventies, in which oral or intraperitoneal administration of various formulations of the papaya plant (Carica papaya L.) during different phases of pregnancy was reported to have exerted a number of effects on pregnancy and embryonic development, such as antiimplantation activity, increased postimplantation loss, and embryotoxicity. In two independent experiments, a well-defined and standardized papain was administered orally to Wistar rats in doses up to 800 mg/kg during blastogenesis (days 0 to 6 of gestation, study 2) or embryogenesis (days 6 to 15 of gestation, study 1). When administered during blastogenesis, the preimplantation loss index was significantly decreased and the number of fetuses was significantly increased in the treated rats. No dead fetuses were found in any test group, and no treatment related increase in postimplantation loss was seen in either study. External, skeletal, and visceral examinations of fetuses did not reveal any important findings. The results of the present investigations lead to the clear conclusion that oral administration of papain up to a dose of 800 mg/kg does not adversely affect prenatal development and does not cause signs of maternal toxicity. PMID- 8520132 TI - Neural tube defects and maternal weight reduction in early pregnancy. AB - We present data from a case series in France of pregnant women who lost 2 to 14 kg during the first month after conception and whose fetuses developed neural tube defects (NTDs). Preliminary epidemiologic evidence from other data sets suggest that relative lack of weight gain during pregnancy may be associated with NTDs. The role of starvation, diabetes, and valproic acid in the etiology of NTDs is established. This etiologic information coupled with our data suggest an hypothesis that ketoacidosis induced by weight loss in early pregnancy is a risk factor for NTDs. PMID- 8520133 TI - An evaluative process for assessing human reproductive and developmental toxicity of agents. PMID- 8520134 TI - The developmental toxicity of indomethacin and sulindac. PMID- 8520135 TI - Orofacial clefts and maternal anticonvulsant use. PMID- 8520136 TI - Evaluation of lift and passive sampling methods during asbestos abatement activities. PMID- 8520137 TI - Red deer antlers as biomonitors for lead contamination. PMID- 8520138 TI - Comparative assessment of two solid-phase toxicity bioassays: the direct sediment toxicity testing procedure (DSTTP) and the Microtox solid-phase test (SPT). PMID- 8520139 TI - Paint as another possible source of lead exposure in Saudi Arabia. PMID- 8520140 TI - Dissipation of three s-triazine herbicides, atrazine, simazine, and ametryn, in subtropical soils. PMID- 8520141 TI - Effects of cationic surfactants on leaching of bromacil and norflurazon. PMID- 8520142 TI - Effects of sublethal exposure to an organophosphate on the flying performance of captive starlings. PMID- 8520143 TI - DDT and its metabolites in Western gull eggs from southern California and northwestern Baja California. PMID- 8520144 TI - Organochlorine residues in gyrfalcons (Falco rusticolus) in Iceland. PMID- 8520145 TI - Mercury contamination of golf courses due to pesticide use. PMID- 8520146 TI - Heavy metal concentrations in great blue heron fecal castings in Washington State: a technique for monitoring regional and global trends in environmental contaminants. PMID- 8520147 TI - Aluminum tolerance of Pseudomonas fluorescens in a phosphate-deficient medium. PMID- 8520148 TI - Waterborne lead affects circadian variations of brain neurotransmitters in fathead minnows. PMID- 8520149 TI - Acute toxic effect of River Yodo water (Japan) on Daphnia magna. PMID- 8520150 TI - Effect of gamma-hexachlorocyclohexane on amylolytic microorganisms of soil and amylase activity. PMID- 8520151 TI - Monitoring of organophosphorus insecticides in the Guadalete River (southern Spain). PMID- 8520152 TI - Susceptibility of mink to methemoglobin formation. PMID- 8520154 TI - Comparison of the toxicity of a synergized and non-synergized insecticide to young trout. PMID- 8520153 TI - Mutagenic activity of the amido derivatives and their hydroxamic acids of nitrobiphenyl ethers. PMID- 8520155 TI - n-Alkanes and polynuclear aromatic hydrocarbons in fresh-frozen and precooked frozen mussels. PMID- 8520156 TI - Comparison of three lipid extraction methods for fish. PMID- 8520157 TI - Acute toxicity of nitrite in juvenile grass carp modified by weight and temperature. PMID- 8520158 TI - Preventive effect of simultaneously infused lipid emulsion against thrombophlebitis during postoperative peripheral parenteral nutrition. AB - A prospective, randomized study was conducted to determine whether simultaneous infusion of lipid emulsion with an amino acid-dextrose-electrolyte solution would reduce the incidence of thrombophlebitis (TP) during postoperative peripheral parenteral nutrition (PPN). Thirty patients who had undergone gastric resection for adenocarcinoma were randomly divided into two groups according to whether they were infused with 10% lipid emulsion (group A) or 5% glucose solution (group B) simultaneously with the amino acid-glucose solutions. The total osmolarity of the infusion solutions in each group was 853 mOsm/l. The incidence of complications due to TP, namely, redness and/or edema beneath the cannula insertion site and/or pain, was investigated. There were no differences in the background characteristics of the patients in groups A and B, except regarding concurrent resection of other organs (P = 0.03). The incidence of edema in group A was significantly lower than in group B on postoperative days 2 and 4, although there was no difference in the incidence of redness and pain between the two groups. These findings suggest that the simultaneous infusion of lipid emulsion has a preventive effect against TP during postoperative PPN, and may be a practical means of providing PPN after gastrointestinal surgery. PMID- 8520159 TI - Severity and predicted outcome of postoperative Pseudomonas aeruginosa infections. AB - The severity and predicted outcome of postoperative Pseudomonas aeruginosa (P. aeruginosa) infections (PPAI) was evaluated using a severity scoring system based on a simplification and modification of the APACHE II system. A total of 86 patients in whom P. aeruginosa was isolated from various sources were examined. PPAI developed in 50 patients, resulting in an overall mortality rate of 24%. An increased severity score (SS) correlated with an increased risk of developing PPAI. Thus, PPAI developed in 33% of the patients with an SS of 0-1, in 66.7% of those with an SS of 2-3, and in 100% of those with an SS of 6 or higher. Moreover, the mortality rate of the patients with an initial score of 6 or higher was 50%. The mean (+/- SD) initial severity score was 5.4 +/- 2.9 for survivors and 2.9 +/- 2.6 for nonsurvivors (P < 0.01). In the patients who subsequently died, the SS remained high throughout the clinical course despite therapy, whereas in the survivors the SS decreased progressively, reflecting a favorable clinical course. These results suggest that our severity scoring system was useful for predicting outcome and monitoring the response of PPAI to therapy. PMID- 8520160 TI - A new method of performing continuous intraabdominal drainage after pancreaticoduodenectomy. AB - Dehiscence of the pancreaticoenterostomy is one of the most feared, yet common, postoperative complications following pancreaticoduodenectomy (PD). We report herein a new technique we developed for performing continuous intraabdominal suction drainage (CISD) following PD. This method of CISD involves positioning an 18 Fr sump tube beside the pancreaticoenterostomy, with a continuous suction pressure of about -20cmH2O. The fluid obtained from the sump tube is also useful for monitoring amylase levels and providing bacterial cultures to enable the early detection of dehiscence of pancreaticoenterostomy. A study was conducted on 150 patients who underwent PD for periampullary carcinoma over a 20-year period. The patients were divided into two groups according to whether or not CISD was performed: group 1 comprised 71 patients who had CISD, and group 2 79 patients who did not have CISD. Although the frequency of anastomotic dehiscence did not differ between the two groups (32% in group 1 and 25% in group 2), the mortality rate of the patients with anastomotic leakage in group 1 was lower than that in group 2 (P = 0.07). Thus, we believe that our new technique for performing CISD could improve the surgical outcome of patients following PD. PMID- 8520161 TI - Clinical usefulness of an ATP heat sensitivity test using endoscopic biopsy materials from esophageal cancer patients. AB - The usefulness of a heat sensitivity test which involved performing an ATP assay on endoscopic biopsy materials for predicting the clinical response to hyperthermia was investigated in esophageal cancer patients. Following in vitro heat treatment of FM3A tumor cells, the heat sensitivity detected by ATPA was significantly correlated with that in the colony-forming assay, and the percent inhibition of the ATP level in the tumor cells was correlated with in vivo tumor growth. The heat sensitivity of the biopsy materials evaluated by ATPA correlated well with that of the resected specimens in 18 esophageal cancer patients, while the clinical response to thermal therapy was well predicted by the heat sensitivity of the biopsy materials evaluated by ATPA in seven of the patients. These results indicate that the heat sensitivity test conducted by performing an ATPA on endoscopic biopsy materials could be a useful indicator for predicting the clinical response to thermal therapy. PMID- 8520162 TI - Extracorporeal membrane oxygenation for respiratory failure. AB - We report herein our experience with extracorporeal membrane oxygenation (ECMO) for respiratory failure over a 3-year period. ECMO was employed in seven patients: in five for respiratory failure caused by adult respiratory distress syndrome (ARDS), Goodpasture's syndrome, hypoxia after ventricular septal defect closure, interstitial pneumonia, or lung metastasis from choriocarcinoma; and in two for tracheal obstruction. Nafamostat mesilate was used as the main anticoagulant with a small amount of heparin. The period of ECMO support for the five patients with respiratory failure ranged from 54 to 251 h, with an average time of 125 h. Five of the seven patients were able to be weaned from ECMO, and the two who had tracheal obstruction survived. The other three patients who were weaned from ECMO died of underlying diseases or complications 1-25 days after weaning. The complications which occurred during ECMO support were an abnormal electroencephalogram, multiple organ failure, and mediastinitis. Thus, we conclude that ECMO needs to be induced early to obtain a better outcome in patients with respiratory failure, and that it is particularly effective for transient airway obstruction. PMID- 8520163 TI - Effects of hypothermia and hyperpotassium on alveolar fluid clearance in the resected human lung. AB - The effect of hypothermia and hyperpotassium on alveolar fluid clearance in the resected human lung was examined by instilling an isosmotic albumin solution with a potassium concentration of 0.3 mEq/l or 20 mEq/l into one segment of a resected lobe within 10 min of surgical removal for bronchogenic carcinoma. The experiments were carried out at 37 degrees C, 25 degrees C, and and 8 degrees C over 4 hr, after which the alveolar fluid was aspirated. Alveolar fluid clearance was calculated by a simple equation using the changes in the albumin concentration of the alveolar fluid. It was found that although hypothermia at 8 degrees C abolished alveolar fluid clearance completely, alveolar fluid clearance at 25 degrees C was not different from that at 37 degrees C. Moreover, although the potassium concentration increased in the alveolar fluid at 37 degrees C and 8 degrees C, hyperpotassium did not affect the alveolar fluid clearance. These findings indicate that the net transport of potassium leans to influx from the alveolar epithelial cells into the alveolar spaces when the alveolar potassium concentration is low, and to efflux from the alveolar spaces when the alveolar potassium concentration is high. Thus, we conclude that hypothermia abolishes alveolar fluid clearance in resected human lungs, but that the potassium concentration in alveolar fluid does not affect alveolar fluid clearance. PMID- 8520164 TI - Effects of medroxyprogesterone acetate therapy on advanced or recurrent breast cancer and its influences on blood coagulation and the fibrinolytic system. AB - The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF+MPA and MPA groups. Increases in factor X, plasminogen, and alpha 2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system. PMID- 8520166 TI - Effect of celiac and superior mesenteric ganglionectomy on fasted canine colonic motor activity. AB - The role played by extrinsic nerves in colonic motor activity and motor coordination between the small intestine and the colon in the fasting state was investigated in a canine model. To evaluate motor activity before and after celiac and superior mesenteric ganglionectomy (CSMG), seven strain gauge force transducers were implanted in the small and large bowels of five dogs. No significant differences were observed in the frequency, duration, cycle, or migration time of bursts of contractions from the colon (BCC), or in the duration of the quiescent state before and after CSMG. When small intestinal phase III activity reached the ileocecal junction before and after CSMG, a characteristic contractile pattern, namely, small intestinal phase III activity followed by BCC, was observed at the ileocecal junction. Before and after CSMG, 84% and 83% of the small intestinal phase III activity, respectively, was transmitted to the colon as BCC after reaching the ileocecal junction. However, only 19% and 18% of BCC before and after CSMG, respectively, followed small intestinal phase III activity. These results led us to conclude that the extrinsic nerves exert little effect on fasting colonic motor activity and motor transmission from the small intestine to the colon. PMID- 8520165 TI - Predicting the viability of grafted livers in rats through a rapid and sensitive metabolic indicator assessed by 31P-NMR spectroscopy. AB - The present study was undertaken to clarify whether a correlation exists between the hepatic ratio of the beta-phosphorus moiety of ATP (beta-ATP) to inorganic phosphate (Pi), measured by 31P nuclear magnetic resonance spectroscopy 1 h after the reestablishment of portal blood flow, and the survival rate of rats following liver transplantation. This ratio was compared with the arterial ketone body ratio [AKBR (acetoacetate/3-hydroxybutyrate)], which is accepted as a reliable indicator of liver viability. After the transplantation of fresh livers, the 1 week survival rate was 92% and the beta-ATP/Pi ratio was 64% of the normal level. When the liver grafts were subjected to warm ischemia for 25 min or 45 min prior to harvesting, the 1-week survival rate decreased to 43% and 0%, respectively, and the beta-ATP/Pi ratio dropped to 31% and 18% of the normal level, respectively. On the other hand, the AKBR was about 25% of the normal level after transplantation of fresh livers, while it was 37% and 48% after transplantation with 25 min and 45 min of warm ischemia, respectively. However, 4 h after the reestablishment of portal blood flow, the AKBR correlated with the beta-ATP/Pi ratio in both the fresh graft group and the 45-min warm ischemic damage group. These results show that the beta-ATP/Pi ratio provides an accurate evaluation of a graft viability even at an extremely early stage following liver transplantation, and should prove useful for the early diagnosis of primary graft nonfunction after liver transplantation. PMID- 8520167 TI - Suppression of pseudointimal hyperplasia by a novel prostacyclin analogue: beraprost. AB - The aim of this study was to evaluate the effect of a novel prostaglandin I2 analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P < 0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs. PMID- 8520168 TI - Effect of dietary vitamin A on forestomach tumorigenesis during the total and postinitiation stages in mice treated with high- or low-dose benzo(a)pyrene. AB - The effects of dietary vitamin A on forestomach tumorigenesis during the total stage of the initiation and postinitiation periods and during the postinitiation stage were evaluated in ICR/Jcl mice treated with either high or low doses of benzo(a)pyrene (B(a)P). In experiment 1, the animals were initiated with a high carcinogenic dose of B(a)P to a total of 20 mg, while in experiment 2 the animals were treated with a low dose of B(a)P to a total of 2 mg. A control group of animals received no carcinogens. Five different dietary levels of vitamin A supplements were used in each experiment and in the control study. In experiment 1, a high incidence of tumorigenesis was observed in every group, with 74% to 96% developing papilloma and 19% to 46% developing carcinoma. In experiment 2, the incidence of tumorigenesis in the high-dose vitamin A groups, including those given during the total and postinitiation stages, was found to be significantly reduced at 7.4%, compared with that in the low-dose vitamin A group of 57.7% (P < 0.05). These results suggest that a high dietary level of vitamin A can reduce the incidence of tumorigenesis when low carcinogenic dose levels of B(a)P are given in both the total and postinitiation stages. PMID- 8520169 TI - A huge immature cervical teratoma in a newborn: report of a case. AB - A neonate with a large cervical mass was transferred to our hospital at 4 days of age. A computed tomography scan showed a contrast-enhanced solid mass with multiple cystic elements and fine calcification. Ultrasonography also revealed a predominantly solid mass with calcification, containing multiple cysts. These studies suggested a teratoma, but could not rule out a hemangioma. The tumor was removed on the 12th day of life. A pathological study revealed an immature teratoma that demonstrated fetal type cartilage and an immature neural tube. The operative complete removal of a cervical teratoma in neonates is recommended as soon as possible. The management of a pediatric cervical teratoma should also be similar to that of a sacrococcygeal teratoma. The incidence of cervical teratoma in all pediatric teratomas ranges from 2.3%-9.3% in the West, and from 1.6%-8.3% in Japan. PMID- 8520170 TI - Complete response of transverse colon carcinoma to S1, a new chemotherapy agent: report of a case. AB - A complete response to a new chemotherapeutic agent, S1, was achieved in a 64 year-old Japanese man with advanced transverse colon cancer. S1 is a combination of the agents tegafur, 5-chloro-2,4-dihydroxypyridine, and oxonic acid. Because the patient was considered to be a high operative risk due to his poor general condition, S1 was administered at 100 mg/day for 5 days/week over 12 weeks. However, as the serum carcinoembryonic antigen level continued to gradually increase, partial resection of the transverse colon was finally performed. Histopathological study of the resected specimen showed mucin pools in the colon wall with no residual viable cancer cells. No perioperative complications were recognized and the patient is now leading a normal life 6 months after his operation without any signs of recurrence. PMID- 8520171 TI - Appendiceal mucinous cystadenoma associated with pseudomyxoma peritonei and multicystic peritoneal mesothelioma: report of a case. AB - An extremely rare case of mucinous cystadenoma developing to pseudomyxoma peritonei together with multicystic peritoneal mesothelioma is herein reported. The patient was 25-year-old Japanese woman who underwent an appendectomy under the diagnosis of acute appendicitis because of right lower abdominal pain. The patient histopathologically demonstrated appendiceal mucocele with pseudomyxoma peritonei. She underwent a laparotomy in our unit following detailed examinations. Several cystic tumors measuring from 3 to 5 cm in diameter were found in the omentum, and thus omentectomy, partial cecectomy and left oophorectomy were all performed to resect the tumors. Immunostaining and electron microscopy showed the appendiceal lesion to be mucinous cystadenoma, while the peritoneal lesion was multicystic mesothelioma. To our knowledge, this is the first report in the world literature of this rare combination of diseases. PMID- 8520172 TI - Disease-free survival for 9 years after liver resection for stage IV gallbladder cancer: report of a case. AB - We report herein the case of a 66-year-old woman who has survived for more than 9 years without recurrence since undergoing a right trisegmentectomy of the liver with biliary reconstruction using the jejunum for stage IV (T1, N1a, M0, UICC) gallbladder cancer. The resected tumor, which was histologically diagnosed as moderately to poorly differentiated adenocarcinoma, was approximately 8 cm in diameter and infiltrated from the gallbladder to the medial, anterior, and posterior segments of the liver, involving the right hepatic and common hepatic ducts and the right hepatic artery; no intrahepatic distant metastasis was found. Although preoperative imaging diagnosis showed swollen lymph nodes at the hepatoduodenal ligament and paraaortic region, histological analysis of the resected lymph nodes revealed only one metastasis, located at the cystic duct which was involved in the tumor. This case demonstrates that curative resection may be the appropriate surgical intervention for patients with a stage IV tumor and direct infiltration to the liver and surrounding organs but no distant metastases. PMID- 8520173 TI - Surgical technique of laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis. AB - We report herein a new method of performing laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis, using refined surgical techniques. The pyloric tumor was immobilized by grasping the first portion of the duodenum and the anterior wall of the stomach, and electrocoagulation was used prior to incising the pyloric tumor to minimize bleeding during the procedure. Although this technique has been applied in only two patients so far, we present the details herein. We believe that with technical and instrumental refinements, the speed and safety of laparoscopic pyloromyotomy will improve and it will become an alternative to open surgery in pediatric patients. PMID- 8520174 TI - Hypertension: a multietiological disease requires a multifactorial approach. PMID- 8520175 TI - Controversy in the pharmacologic treatment of hypertension in African Americans. AB - In 1993, the National Institutes of Health published the recommendations of the fifth, and most recent, US Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure. Many believe that this report advocates the use of inexpensive diuretics and beta-adrenergic-receptor blocking agents as first-line agents in the pharmacologic treatment of hypertension. It has been argued that this recommendation is engendered by primary concerns about costs rather than efficacy or patient satisfaction. The contrary view, however, contends that new, more expensive therapeutic drugs have not demonstrated long term reductions in morbidity and mortality. For those who train physicians in the treatment of hypertension in African Americans, awareness of this dispute is pivotal so that informed decisions will be made by both the physician and patient. PMID- 8520176 TI - Accuracy and precision of serum gastrin measurements in commercial laboratories. AB - Patients referred to us with "positive" secretin tests and the diagnosis of Zollinger-Ellison syndrome were found to be achlorhydric. This observation led us to study prospectively the accuracy and precision of serum gastrin determinations from commercial laboratories. Synthetic gastrin (G17) was added to serum to achieve gastrin concentrations of 50, 100, 250, 500, 750, 1000, 3000, and 5000 pg/mL after subtraction of the basal value (24 pg/mL). Three aliquots of each concentration were analyzed by radioimmunoassay in our laboratory (Health Science Center at Brooklyn) and sent to four major commercial laboratories that perform 5000 to 25,000 gastrin assays per year. The reported gastrin concentrations of the triplicate samples demonstrate that many commercial laboratories failed to accurately measure gastrin. Commercial laboratories generally reported higher than-actual gastrin concentrations in samples containing less than 500 pg/mL and lower-than-actual gastrin concentrations in samples containing more than 500 pg/mL. Of all aliquots containing 100 pg/mL or less, 14 of 24 samples (58%) were reported by commercial laboratories to contain elevated gastrin concentrations. At gastrin concentrations from 250 to 5000 pg/mL, the range of values (highest- to lowest-reported value for each concentration) was greater than 200 pg/mL in 62% of triplicate samples reported by commercial laboratories. These data indicate that determinations by some commercial laboratories lack the precision required to satisfy the current diagnostic criterion (a postsecretin rise from basal gastrin of 200 pg/mL or greater) for Zollinger-Ellison syndrome. Clinicians should be aware of this problem and obtain more basal serum gastrin samples to allow for an analysis of the range of baseline values prior to secretin injection. PMID- 8520177 TI - Neonatal enterovirus infection. AB - A neonate who had a nonfatal echovirus 11 infection with severe hepatitis, hepatic necrosis, disseminated intravascular coagulation, and thrombocytopenia was seen at the University of Tennessee Medical Center (UTMC) in Knoxville. Clinical data from this neonate were examined and compared with clinical data from histories of 8 other cases of neonatal enteroviral infections seen at UTMC, Knoxville, during a 3-year period. The purpose of our study was to increase awareness of the clinical presentations of neonatal enteroviral infections, especially in summer months. The patients in our study presented with various clinical manifestations of disease, including overwhelming systemic infection characterized by severe hepatic dysfunction and coagulopathy with possible disseminated intravascular coagulation and central nervous system infection. Myocarditis was sometimes manifested as well. In agreement with findings from other studies, our study concluded that most enteroviral infections in neonates resulted from perinatal transmission during delivery where the mothers had experienced recent, febrile, viral-like illness prior to or during delivery. One uncommon finding in our study was that the cases were strikingly seasonal, with 8 of the 9 infants hospitalized during late summer or early fall (July through September). PMID- 8520178 TI - Basal serum follicle stimulating hormone (FSH) and estradiol levels as predictors of pregnancy in unstimulated donor insemination cycles. AB - PURPOSE: The purpose of this study was to evaluate the utility of basal serum follicle stimulating hormone and estradiol levels in predicting pregnancy in women undergoing artificial insemination with donor sperm for severe male factor infertility. METHOD: A retrospective chart review of 48 women who had at least 2 cycles of artificial insemination with donor sperm and who had undergone testing for basal serum follicle stimulating hormone and estradiol levels prior to or during therapy. RESULTS: There was no difference in age or mean basal serum follicle stimulating hormone between women who conceived (clinical pregnancy) and those who did not. Women who conceived had significantly lower mean serum basal estradiol levels (P = 0.02) and significantly fewer numbers of treatment cycles (P = 0.041). The highest pregnancy rate was among those women with normal basal serum follicle stimulating hormone and estradiol levels. Receiver operating characteristic curve analysis revealed basal serum estradiol to be a more reliable predictor of pregnancy than follicle stimulating hormone. CONCLUSIONS: Basal serum follicle stimulating hormone and estradiol levels may be useful in predicting success with artificial insemination with donor sperm. It may be useful to obtain basal serum follicle stimulating hormone and estradiol prior to initiating artificial insemination with donor sperm. PMID- 8520179 TI - The predictive value of serum progesterone and 17-OH progesterone levels on in vitro fertilization outcome. AB - PURPOSE: In order to identify parameters which predict prognosis for success with in vitro fertilization, 17-hydroxyprogesterone and progesterone levels were evaluated in 254 patients undergoing 296 in vitro fertilization cycles. Selected response and outcome data were recorded. RESULTS: Patients with intermediate values of serum progesterone (0.7-0.8 ng/ml) at the time of human chorionic gonadotropin administration achieved significantly higher pregnancy rates than patients with lower (< 0.7 ng/ml) or higher (> 0.8 ng/ml) levels. The clinical pregnancy rates were 46%, 31%, and 27% respectively (P = 0.02). There was no change in 17-hydroxyprogesterone concentration which predicted a higher pregnancy rate. CONCLUSION: Excellent clinical pregnancy rates were noted in cycles with a progesterone level of 0.7-0.8 ng/ml, as well as good results in cycles above 0.8 ng/ml. There is therefore no reason to administer human chorionic gonadotropin at a smaller follicle size to prevent a rise in serum progesterone. PMID- 8520180 TI - Ovulation triggering in clomiphene citrate-stimulated cycles: human chorionic gonadotropin versus a gonadotropin releasing hormone agonist. AB - PURPOSE: To compare the use of human chorionic gonadotropin (hCG) to a gonadotropin releasing hormone (GnRH) agonist, nafarelin, in initiating ovulation and supporting the luteal phase after priming with clomiphene. METHODS: In 26 infertile women 50 mg clomiphene citrate produced a preovulatory-size follicle. Then, 11 women were randomized to receive two 400-micrograms doses of nafarelin intranasally 16 h apart, and 15 women were injected intramuscularly with 5000 IU of hCG (luteal day 0 = LD0). Starting on LD6, 7 more 400-micrograms doses of nafarelin were repeated on an every 16-h schedule or a single 2500 IU dose of hCG was given, respectively. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), and hCG were measured. On LD13, endometrium was evaluated with ultrasonography and biopsy in 19 nonpregnant women. RESULTS: As judged by a threefold rise in serum LH, an LH surge was detected on LD1 in all 11 nafarelin patients, but in only 8 hCG patients (P = 0.01). LH and FSH levels were significantly higher on LD1, 7, and 8 and were significantly suppressed on LD13 in the nafarelin group. All patients had mid-luteal P levels greater than 10 ng/ml and luteal phases longer than 13 days. Significantly different luteal E2 or P levels were noted only on LD13, with lower values in the nafarelin group. Pregnancies were achieved in 3 of 11 nafarelin cycles and 2 of 15 hCG cycles. Luteal phase defects were also similar: 4 of 8 nafarelin patients and 7 of 11 hCG patients. CONCLUSION: Nafarelin or hCG in conjunction with clomiphene can result in viable pregnancies, but is associated with low pregnancy rates and a high incidence of luteal phase defects. PMID- 8520181 TI - A new long shelf life formulation of modified Ham's F-10 medium: biochemical and clinical evaluation. AB - PURPOSE: To evaluate biochemically and clinically a new formulation of modified Ham's F-10 medium made without the inclusion of hypoxanthine. The medium was formulated for long-term storage and use by separately preparing a stable liquid ("basal") portion and a freeze-dried "supplement" containing the labile medium components. RESULTS: Following 18 months of storage the basal medium was biochemically analyzed for its amino acid (aa's) and vitamin content. Cysteine and tryptophan were decreased to less than 30% of their starting theoretical concentrations (STCs). Asparagine, serine, tyrosine, histidine and lysine were present at 50% to 70% of their STC. The remaining aa's were all within 90% of their STCs except arginine which was at 77%. All of the vitamins were present at 90% or more of their STCs except inositol, riboflavin and thiamine which were present at 70% of their STCs. IVF with the new formulation resulted in 13 deliveries from 51 aspirations (25%) as compared with 10/39 (26%) in 1991, when standard medium preparation was used. Oocyte donation resulted in 30 deliveries from 84 cycles (36%) with the new formulation as compared with 21/65 (32%) in 1991. CONCLUSIONS: (1) The new basal with lyophilized supplement formulation produces similar clinical results in the IVF laboratory as medium prepared in the standard fashion, (2) certain amino acids and vitamins are not stable in the liquid basal medium, and (3) the separate formulation of a liquid basal medium with lyophilized supplement is convenient, viable alternative to modified Ham's F 10 medium prepared in the standard manner (i.e., from powder) and may decrease the need for frequent medium preparation. PMID- 8520182 TI - Hormone release from cultured luteinized-granulosa cells mimics differences seen in vivo in patients undergoing IVF-ET. AB - OBJECTIVES: Previous research from this laboratory has suggested that a relationship exists between the increase in circulating progesterone concentrations at the time of hCG administration and cycle outcome in patients undergoing IVF. Progesterone (P) increases of threefold or better within the 24-h period surrounding hCG administration appeared to be associated with a higher pregnancy rate. These data suggest a functional difference in the luteinized granulosa of patients undergoing IVF. To test this hypothesis: DESIGN: A split split plot arrangement of treatments with two cell sources under five hormonal stimulations at four time points. METHODS: Luteinized-granulosa cells (LGC) were collected from patients with either a normal increase (> or = threefold = NC) in circulating P (n = 4) or those with lower P increases (AC; n = 4). The cells were isolated by Ficoll gradient centrifugation and then cultured in 24-well culture plates using a modified media 199 containing 100 mIU/ml of hMG, FSH, LH, hCG, or a nonhormonal control to stimulate steroid-hormone production. At time points 2, 4, 6, and 8 days, media from each well was frozen for later hormone assay and replaced with fresh media containing the same stimulating factor. After all the media had been collected, P and estradiol (E2) released into the media were measured using radioimmunoassay. RESULTS: Results indicate a higher media concentration of P (P < 0.001), but not E2 (P = 0.254), from NC, regardless of hormone stimulation or time in culture, when compared to the media from AC. Media concentrations of E2 were affected by a cell source by hormone stimulation by time interaction (P < 0.001) with varying effects. Media from NC maintained a constant E2 of between 1000-3000 pg/ml over the 8-day period (P = 0.163). However, media from AC demonstrated a stimuli-dependent E2 release (P < 0.001) ranging from < 1000 to over 11,000 pg/ml. CONCLUSIONS: These data appear to support the existence of functionally different populations of luteinized granulosa cells from patients undergoing IVF-ET. PMID- 8520183 TI - Epidural anesthesia in an in vitro fertilization and embryo transfer program. AB - OBJECTIVES: To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program. STUDY DESIGN: Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide). RESULTS: In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant. CONCLUSIONS: Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide. PMID- 8520184 TI - Cumulative birth rates following cryopreservation of all embryos in stimulated in vitro fertilization (IVF) cycles. AB - OBJECTIVE: To cryopreserve all good-quality embryos available after IVF is one way to avoid an impending hyperstimulation and a more attractive alternative to a couple than cancellation of the cycle. At Sahlgrenska University Hospital this method has been practiced since 1991. The aim of this study was to assess the success rate (defined as childbirth per couple) after IVF treatment including one stimulated cycle, resulting in cryopreservation of all good-quality embryos available, followed by replacement of frozen/thawed embryos in one or more natural cycles. DESIGN: A cohort of 32 women undergoing one stimulation for IVF between January 1991 and December 1993 where all good-quality embryos were cryopreserved and transferred in a later spontaneous cycle were studied retrospectively. The cumulative childbirth rate per couple was calculated. RESULTS: A total of 28 women underwent a total of 45 transfers with frozen-thawed embryos. In 4 women no transfer has taken place so far. The clinical pregnancy rate per embryo transfer was 33% (15/45) and per patient 54% (15/28). Three spontaneous abortions occurred giving a cumulative childbirth rate per patient of 39% (11/28). In addition, 6 out of the 28 women still have embryos left in the freezer. CONCLUSION: Cryopreservation of all good-quality embryos available after IVF is a highly effective alternative to cancellation of a cycle when there is impending hyperstimulation. The use of this approach results in a cumulative childbirth rate per couple of at least 39%. Since only one stimulation was performed, it also seems to be cost effective. PMID- 8520185 TI - Progesterone concentration as a predictor of pregnancy normalcy is the most useful when hCG levels are less than 2000 mIU/mL. AB - OBJECTIVE: Measurements of serum progesterone to predict early gestational normalcy have been found to be as predictive as serial hCG titers. Since ultrasound would be the diagnostic tool of choice if hCG was > 2000 mIU/ml, the purpose of the present study was to determine the best predictive value of a single progesterone measurement when hCG levels were < 2000 mIU/ml. DESIGN: Relative operating characteristic analysis of progesterone level as a predictor of early gestational normalcy when hCG is < 2000 mIU/ml. MATERIALS AND METHODS: Ninety-three pregnant patients that conceived spontaneously were evaluated with progesterone measurements when the patient's hCG was < 2000 mIU/ml. Two-by-two contingency tables were constructed that compared pregnancy outcome with multiple discriminatory serum progesterone concentrations between 0 and 38 ng/mL. From these tables, a relative operating characteristic (ROC) curve was generated to compare the sensitivity and false-positive rates. RESULTS: Of a total of 93 pregnancies, 27 had a normal outcome and 66 had an abnormal outcome. The ROC curve indicated that a serum progesterone concentration of 12 ng/ml had the highest sensitivity associated with the lowest false-positive rate. The area under the curve was equal to 0.941 +/- 0.024. This observation was compared to our previously reported data of progesterone levels that included hCG levels > 2000 mIU/ml, yielding an area under the curve of 0.772 +/- 0.053. Calculation of the critical ratio z revealed that there is a significant improvement in the predictive value of progesterone when hCG is < 2000 mIU/ml (P < 0.005). CONCLUSION: A single serum progesterone level has a better predictive value of pregnancy normalcy when hCG measurements are < 2000 mIU/ml. PMID- 8520186 TI - Estrogen and progesterone receptor mRNA are expressed in distinct pattern in male primate reproductive organs. AB - PURPOSE: The role(s) of estrogens (E) and progesterone (P) in male reproductive physiology remain unclear. Estrogens are used in the treatment of prostatic cancer. Progestins have been used to control excessive sexual behavior in men, and proposed as a male contraceptive. Previous immunohistochemical studies have shown that E receptors (ER) are present in the reproductive tract of male nonhuman primates. METHOD: We examined the expression pattern of ER and progesterone receptor (PR) mRNA in adult primate male reproductive tract. mRNA was extracted from male pituitary, testis, prostate and different regions of the epididymis of three intact adult cynomolgous monkeys. Ovarian, myometrial and spleen mRNA were used as controls. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify ER and PR mRNA; beta-actin mRNA was used as a reference. Primers for ER, PR and beta-actin were designed using the most conserved areas in the corresponding human cDNA sequences, and the identity of the PCR products was verified using Southern hybridization. Semiquantitative analysis of ER and PR mRNA content in different parts of the male reproductive tract was carried out by spiking the PCR reaction with 33P-dCTP, and amplifying the samples for 20 cycles with the beta-actin primers, whereas 30 cycles were used for ER and PR. RESULTS: The results are expressed as cpm ratios of ER or PR/beta-actin. All the male reproductive organs studied revealed a strong signal for ER and PR mRNA. The results of the semiquantitative analysis indicate that the expression of both ER and PR was highest in testis (mean +/- SE 6.4 +/- 1.3 and 0.5 +/- 0.1, respectively). The mean figures for prostate were 0.5 and 0.4, respectively. The mean content of ER and PR in the different areas of epididymis was 0.5 and 0.1, respectively. The epididymal ER mRNA was highest in the corpus region (ER/beta-actin 0.7), the ratio being 0.4 for the caput and cauda regions. The expression pattern of PR mRNA was different, and the caput of epididymis being the most intense (0.2). Surprisingly, the pituitary content of ER and PR mRNA was close to that seen in the ovary, the mean +/- SE values being 7.6 +/- 0.5 and 1.3 +/- 0.1, respectively. CONCLUSIONS: We, therefore, conclude that male monkey reproductive tract contains mRNA for ER and PR, and there appears to be regional variation in their expression. Thus the role(s) of Es and P in male reproductive physiology, specifically in sperm maturation, warrants further investigations. PMID- 8520188 TI - Treatment by assisted conception of severe male factor infertility due to spinal cord injury or other neurologic impairment. AB - PURPOSE: This retrospective study evaluated the pregnancy rates of 23 couples with male factor infertility due to traumatic spinal cord injury (N = 21), multiple sclerosis (N = 1) or transverse myelitis (N = 1). METHODS: Ovulation induction by clomiphene citrate or gonadotropins was used in combination with intrauterine insemination as an initial approach for assisted conception in all but one couple. RESULTS: Six pregnancies occurred in 60 cycles of intrauterine insemination (mean of 2.6 cycles). In this group, the cumulative pregnancy rate was 26%. Six couples who failed after a total of 33 intrauterine insemination cycles (mean of 5.5 cycles), and 1 couple with no previous intrauterine insemination cycles, initiated 10 cycles of in vitro fertilization (mean of 1.4 cycles). In this group, five pregnancies occurred. The pregnancy rate was 71%. CONCLUSION: We conclude that ovulation induction in combination with intrauterine insemination offers an effective initial therapy of severe male factor infertility due to spinal cord injury. PMID- 8520187 TI - Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome. AB - PURPOSE: To further investigate the efficacy of progesterone in the treatment of the symptoms of premenstrual syndrome (PMS). MATERIALS AND METHODS: From an initial cohort of 25 subjects diagnosed with moderate to severe PMS, 17 reproductive age females completed the 7-month, double-blind, placebo controlled trial using 200-mg vaginal progesterone suppositories. Multiple modalities for evaluating symptoms were employed, including the Spielberger self-evaluation rating, the Beck depression inventory, and the Hamilton anxiety scale. In addition, each subject was interviewed by a psychiatrist on a monthly basis; ovulation was determined monthly using a basal body temperature chart; serum hormonal assays included beta endorphin, progesterone, follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin. RESULTS: Hormonal assays confirmed no differences between treatment and control groups. Overall scores on all test vehicles were likewise not significantly different between the two groups; however, in the subcategory of nervous symptoms, a significant improvement was found in symptoms relating to tension, mood swings, irritability, anxiety and lack of control. CONCLUSIONS: Metabolites of progesterone (pregnanolone and allopregnanolone) may play a physiologic role as anxiolytic agents, perhaps modifying mood and anxiety; the current study confirms the utility of twice daily, 200-mg progesterone vaginal suppositories, in the alleviation of some PMS symptoms relating to anxiety and irritability. Further evaluation may be warranted to ascertain which patients in the known heterogeneous PMS population may be most likely to benefit from such treatment. PMID- 8520189 TI - The effect of nicotine on in vitro sperm motion characteristics. AB - PURPOSE AND STUDY PLAN: Men who are habitual smokers tend to have poor semen quality. We studied the effect of nicotine on sperm motility in vitro. Spermatozoa from 13 normal fertile nonsmoking donors, washed free of seminal plasma, were treated with medium alone (control); and, 10 mM, 5 mM, 1 mM and 0.1 mM nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers). Computerized sperm motion analysis (CASA) was done at 2, 4, 6 and 24 h after incubation. RESULTS: Sperm motility, beat/cross frequency, linearity and maximum anterior lateral head displacement (ALH max.) were significantly decreased across nominal dosages (P < 0.001 by repeated measures analysis of variance). Of the concentrations tested, 0.1 mM had no effect; 1 mM significantly decreased sperm motility (P = 0.003) and linearity (P = 0.02); 5 mM decreased the beat frequency (P = 0.001) and linearity (0.02); and 10 mM markedly decreased motility (P = 0.0001), beat frequency (P = 0.0002), linearity (P = 0.02) and ALH max. (P = 0.02). The interactions between dose and time were insignificant. CONCLUSION: Nicotine at concentrations of > or = 1 mM significantly decreased sperm motion characteristics after different periods of incubation, whereas 0.1 mM concentration had the least effect. PMID- 8520190 TI - Luteal estrogen is not required for the establishment of pregnancy in the human. PMID- 8520191 TI - High success with gestational carriers and oocyte donors using synchronized cycles. AB - PURPOSE: Our purpose was to determine if exogenous hormone stimulation of the endometrium improves the implantation and pregnancy rate with a host uterus or gestational carrier. RESULTS: Nine couples underwent 14 embryo transfer cycles with a gestational carrier. The median age was 31.3 years for the infertile women donating the oocytes and 36.6 years for the gestational carriers. Eight pregnancies were achieved documented by ultrasound confirmation of cardiac activity. The pregnancy rate was 64.3%, with 1.6 cycles per patient. CONCLUSION: We show that synchronized exogenous hormone stimulation of the gestational carrier improves the success rate of embryo transfer. When the success rate is compared to a timed embryo transfer with the gestational carrier's natural cycle, from previous reported studies, exogenous hormonal stimulation appears to enhance endometrial receptivity and improve the implantation rate. PMID- 8520192 TI - Ovarian activity during follicular-phase down regulation in in vitro fertilization is associated with advanced maternal age and a high recurrence rate in subsequent cycles. AB - PURPOSE: Previous reports have suggested that the ovarian response to leuprolide acetate is predictive of in vitro fertilization pregnancy rates. This study evaluated the outcome of in vitro fertilization cycles complicated by elevated estradiol levels during leuprolide acetate down regulation and the outcome of subsequent cycles in the same patients. METHODS: Two hundred fifty-two in vitro fertilization cycles were initiated utilizing leuprolide acetate down regulation beginning on cycle day 1. RESULTS: Seventy-four of these cycles had an elevated estradiol level at the time of the baseline scan (28%). This group of patients had a higher maternal age, a higher cycle cancellation rate (27.5 vs 16.3%), and a high rate of recurrence on subsequent cycles (63%). CONCLUSIONS: The pregnancy rate per retrieval was equivalent in the two groups. This suggests that patients with advanced maternal age or a history of failure to suppress in a previous cycle may benefit from alternate regimens of superovulation. PMID- 8520193 TI - Evaluation of serum-associated embryotoxicity in women with reproductive disorders. AB - PURPOSE: Our purpose was to determine whether some cases of infertility may be due to serological factors inhibiting development of the embryo. METHOD: We examined the effect of infertile women's sera on the expansion, attachment, and spreading of mouse blastocysts in culture. Cell marker expression was also assayed by an indirect immunofluorescence technique. Serum samples from 75 infertile women were compared to the effect of 24 control AB sera. RESULTS: After 72 hr, blastocyst spreading was significantly different depending on whether cultured in sera from women with unexplained infertility, anovulatory infertility, diethylstilbesterol exposure or controls. Neither sera from women with mechanical infertility (14) nor sera from women with endometriosis (8) affected blastocyst growth in culture. CONCLUSIONS: Inhibitory sera were capable of reducing cytokeratin expression but had no effect on placental alkaline phosphatase or concanavalin A expression by blastocyst cells. It can be inferred that the inhibitory effect of sera from women with certain types of infertility might be due to damage to the cytoskeleton. This in vitro assay may predict the success or failure of IVF. PMID- 8520194 TI - Sperm stimulants can improve fertilization rates in male-factor cases undergoing IVF to the same extent as micromanipulation by partial zona dissection (PZD) or subzonal sperm insemination (SUZI): a randomized controlled study. AB - PURPOSE: Our purpose was to evaluate the efficacy of direct insemination (IVF), micromanipulation by partial zona dissection (PZD), and subzonal sperm insemination (SUZI) using sperm-treated with pentoxifylline (PF) +/- 2 deoxyadenosine (2DA). RESULTS: The overall fertilization rate achieved was similar for all three fertilization techniques (33.1, 30.2, and 26.9% for IVF, SUZI, and PZD, respectively). Patients who had reduced fertilization in previous IVF attempts showed improved fertilization with sperm stimulants, either PF alone or PF in combination with 2DA in standard IVF. In certain cases, SUZI or PZD gave significantly improved fertilization rates in comparison to IVF. CONCLUSION: Selective use of sperm stimulants in IVF can achieve fertilization for the majority of male-factor cases. However, PZD and SUZI techniques are useful, especially when sperm stimulants fail to achieve fertilization or achieve poor fertilization in direct insemination. PMID- 8520195 TI - A randomized study of intracytoplasmic sperm injection (ICSI) versus subzonal insemination (SUZI) for the management of severe male-factor infertility. AB - OBJECTIVE: Our objective was to compare the fertilization rates achieved by ICSI versus SUZI in couples with severe male infertility. DESIGN: This was a randomized, prospective study. SETTING: The study took place at the In-Vitro Fertilization-Embryo Transfer Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center. MATERIALS AND METHODS: Oocytes of 12 patients were randomly allocated to either ICSI or SUZI procedures. Each woman thus served as her own control. All 12 patients had undergone at least two previous in vitro fertilization cycles with no fertilization or had a very low sperm count, i.e., a total motile sperm count of less than 0.5 x 10(6). RESULTS: A total of 117 oocytes was obtained for fertilization. Of these oocytes, 16% (10/63) were successfully fertilized by SUZI, compared to 33% (18/54) treated by ICSI. This difference was statistically significant (P < 0.05). Of the 12 cycles, ICSI provided embryos in 10 cycles (83%), while SUZI was successful in only 6 cycles (50%). Four pregnancies were achieved: 33% per attempt, or 40% per transfer. PMID- 8520196 TI - Cytogenetic analysis of uncleaved oocytes after intracytoplasmic sperm injection. AB - PURPOSE: This work analyzes the causes of cleavage failure after intracytoplasmic sperm injection (ICSI) and the effect of the procedure on the chromosomes of the oocytes. METHODS: Ninety-seven uncleaved oocytes from 39 patients with severe male infertility or repeated IVF failure were fixed; 79 were analyzable. We checked the decondensation stage of spermatozoa nucleus and the chromosomal abnormalities of the oocytes. RESULTS: Among the fixed oocytes, the spermatozoa nucleus was present in 97% of the cases, and it was undecondensed in 89% of the cases, showing no evolution at all. A low rate (2.6%) of premature chromosome condensation (PCC) of the spermatozoa and a low rate (2.5%) of female diploidy were observed. Among the oocytes that could be karyotyped, we observed a high rate (45%) of chromosome breakage. CONCLUSION: ICSI fertilization failure was due mostly to the complete lack of evolution of the spermatozoa nucleus. Oocyte selection before ICSI seemed to lower the PCC rate. The high rate of oocyte chromosomal breakage rate has to be confirmed. PMID- 8520197 TI - Angiotensin converting enzyme inhibition of the gonadotropin-stimulated rabbit: effect on estradiol production. AB - PURPOSE: Our purpose was to determine whether angiotensin converting enzyme (ACE) inhibitors affect gonadotropin-stimulated estradiol (E2) production. DESIGN: This was a prospective, masked, randomized, placebo-controlled animal trial. Twenty female New Zealand White rabbits were hyperstimulated with gonadotropins. One half of the rabbits received concomitant treatment with the ACE inhibitor, enalapril; one-half received concomitant treatment with a placebo. RESULTS: Baseline peripheral E2 (13 +/- 4 vs 11 +/- 2 pg/ml) and angiotensin II (Ang II) (22 +/- 5 vs 27 +/- 7 pg/ml) levels were similar in both groups. Significant inhibition of peripheral Ang II levels was achieved in the enalapril group (32 +/ 6 vs 93 +/- 15 pg/ml; P = 0.005). E2 was significantly higher in the rabbits receiving enalapril versus placebo (369 +/- 58 vs 183 +/- 35 pg/ml, P < 0.03), respectively. By day 10, peripheral E2 had returned to normal levels in both groups (13 +/- 1 vs 13 +/- 1 pg/ml). However, E2 levels in the ovarian effluent were 2.8 times higher in the enalapril rabbits. CONCLUSION: Peripheral Ang II levels increase after gonadotropin stimulation and ACE inhibitors are able to blunt this increase significantly. ACE inhibition has a significant stimulatory effect on ovarian E2 production. This implies that Ang II may normally inhibit ovarian E2 production in stimulated cycles. PMID- 8520198 TI - Effects of platelet activating factor on mouse embryo implantation in vitro. AB - PURPOSE: Our purpose was to assess the role of platelet activating factor (PAF) in embryo implantation, we examined the effects of PAF and a PAF antagonist on the in vitro implantation of mouse embryos, using an in vitro embryo culture system in the absence of the endometrium. METHODS: BDF1 mouse pronuclear-stage embryos were cultured until they developed to the two-cell, the four- to eight cell, or the morula stage in the absence of PAF or its antagonist CV6209. The medium was then changed and supplemented with PAF or CV6209 at various concentrations. We also examined the reversible effects of PAF addition to the media containing the PAF antagonist. RESULTS: The addition of PAF to the culture from the two-cell stage significantly (P < 0.05) increased the rates of embryo implantation in vitro (control, 69.8%; 10(-10) M PAF, 90.1%; 10(-9) M PAF, 95.5%). Similarly, the addition of PAF to the cultures from the four- to eight cell and morula stage also significantly (P < 0.05) increased their rates of implantation in vitro. In contrast, the addition of CV6209 to the culture significantly (P < 0.01) decreased the rates of embryo implantation in vitro. CV6209 also decreased the rate of blastocyst formation. The degree of inhibition by CV6209 decreased with the advancing stage of embryos. The addition of PAF to media containing CV6209 reversed the inhibition and restored the implantation rate in vitro. CONCLUSIONS: These results suggest that PAF may act directly on the mouse embryo and favor its implantation like an autocrine activating factor, irrespective of the presence or absence of the endometrium. PMID- 8520199 TI - Acute arterial thrombosis after gamete intrafallopian transfer: a case report. PMID- 8520201 TI - Pregnancy achieved by intracytoplasmic injection of cryopreserved epididymal sperm microsurgically aspirated from a man with long-term vasectomy. PMID- 8520200 TI - Induced hypoestrogenism increases the arterial resistance index of leiomyomata without affecting uterine or carotid arteries. PMID- 8520202 TI - Ovarian hyperstimulation syndrome complicated by uterine prolapse. PMID- 8520203 TI - Use of liquid chromatography for the determination of interactions between bioactive compounds. AB - Molecular interactions can be easily determined both by thin-layer and high performance liquid chromatography. The theory and practice of the determination of molecular interactions and the various methods for the calculation of complex stability are presented. Examples of the application of liquid chromatographic methods for the measurements of molecular interactions are also discussed. PMID- 8520204 TI - Determination of free fatty acids in blood, tagged with 4-(2-carbazoylpyrrolidin 1-yl)-7-(N,N-dimethylaminosulfonyl )- 2,1,3-benzoxadiazole, by high-performance liquid chromatography with fluorescence detection. AB - The free fatty acids in blood were determined by high performance liquid chromatography (HPLC) after pre-column tagging with 4-(2-carbazoylpyrrolidin-1 yl)- 7-(N,N-dimethylaminosulphonyl)-2,1,3-benzoxadiazole [sequence: see text] (DBD-ProCZ). The tagging conditions were optimized with palmitic acid (C16:0) and linoleic acid (C18:2) as representative free fatty acids, saturated and unsaturated, respectively. Under the mild reaction conditions of room temperature for 90 min in dimethylformamide (DMF) containing 1-ethyl-3-(3 dimethylaminopropyl)-carbodiimide hydrochloride (EDC, 0.2 M)/pyridine (2%), all the fatty acids tested were tagged with the DBD-ProCZ to produce highly fluorescent derivatives which emit light at 550 nm (excitation at 450 nm). The fluorescence wavelengths were essentially the same for all fatty acids, whereas the intensities were different for individual fatty acids. The derivatives obtained from ten free fatty acids were completely separated by reversed-phase chromatography with two isocratic elution conditions. The on-column detection limit (signal-to-noise ratio of 3) with proposed HPLC separation and fluorescence detection is in the range of 19 (palmitic acid)--176 fmol (palmitoleic acid). The free fatty acids in rat serum and human plasma were successfully determined using the present methods. PMID- 8520205 TI - Determination of argininosuccinate lyase in human serum by ion-pair reversed phase liquid chromatography. AB - A new assay for argininosuccinate lyase based on the separation of the enzymatic reaction mixture components by an ion-pair reversed phase mechanism is reported. The determination of enzyme activity is performed after direct injection by UV detection of the fumarate formed. The chromatographic analysis time is 8 min and a detection limit of 0.4 U/L is achieved. The HPLC method is highly accurate, sensitive and precise. The simple procedure makes this method suitable for the routine determination of ASAL activity in human serum samples. PMID- 8520206 TI - TLC characterization of liposomes containing D-myo-inositol derivatives. AB - The thin-layer chromatographic (TLC) behaviour of liposomes containing inositol phosphates (IPs) was studied. The liposomes contained different concentrations of D-myo-inositol 1,4,5k-trisphosphate (IP3), D-myo-inositol 1,2,6-trisphosphate (alpha-trinositol, PP 56, a novel Perstorp Pharma derivative), D-myo-inositol 1,3,4,5-tetrakisphosphate (IP4), D-myo-inositol 1,3,4,5,6-pentakisphosphate (IP5) and D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Migration of all liposome batches was compared to that of control liposomes (containing only triple distilled water), and to that of free phosphatidylcholine (PC); the same amount of lipid was used in all situations. Thin-layer chromatography was performed on silica gel as adsorbent. As solvent we used an n-buthanol:ethanol:water mixture in a 4:3:3 volume ratio. Significant differences were found between PC and all liposome batches, as well as between control liposomes and the ones containing IP3, alpha-trinositol, IP4, or IP5, in various concentrations. Liposomes containing IP6 migrate completely differently compared not only to phosphatidylcholine and control liposomes, but also to the ones containing other IPs ( < 10(-3) M). Unlike the other IPs studied, liposome-entrapped IP6 elicits dose-dependent contractions of the isolated rat aorta. This suggests that liposomes loaded with IP6 undergo, during or after their preparation, physico chemical alterations that eventually change their drug-delivery capacity. PMID- 8520207 TI - The quantitative analysis of inhalational anaesthetics in forensic samples by gas chromatography/mass spectrometry/selected ion monitoring. AB - The quantitative analysis of volatile anaesthetics for biomedical applications by means of gas chromatograph/mass spectrometry/selected ion monitoring (GC/MS/SIM) was studied. Xenon gas was selected as an internal standard for the assay by adding to a closed system, because of its stability and inactivity. In the assay of inhalational anaesthetics, isoflurane and nitrous oxide (laughing gas), in forensic samples (serum and cerebrospinal fluid), the calibration of the anaesthetic was linear from 0.12 to 12 nmol/mL in isoflurane and from 30 to 300 nmol/mL in nitrous oxide. Our results suggest that this new method is suitable for the quantitative analysis of inhalational anaesthetics in the biomedical field. PMID- 8520208 TI - Identification of 9,10-epoxyoctadecanoic acid in human urine using gas chromatography-mass spectrometry. AB - 9,10-epoxyoctadecanoic acid has been detected in human urine. Two simple purification procedures were used; the one based upon liquid-liquid extraction and the other based upon sorbent extraction technology isolating the free fatty acid fraction. Prior to trimethylsilylation and gas chromatographic-mass spectrometric analysis, both the epoxy and carboxy functions were reduced to hydroxy groups. The shift in fragmentation of a deuterated sample verified the presence of intact epoxide prior to chemical reduction. Special attention was paid to the risk of false identification of the epoxide. The content of 9,10 epoxyoctadecanoic acid in human urine was estimated to be 2.1 nM/L. PMID- 8520209 TI - Determination of medetomidine, atipamezole and midazolam in pig plasma by liquid chromatography-mass spectrometry. AB - Medetomidine, atipamezole and midazolam in pig plasma were determined by liquid chromatography-mass spectrometry (LC-MS) with an atmospheric pressure chemical ionization interface system by the use of detomidine as an internal standard. The method was applied to studies of pharmacokinetic behaviour of these drugs. PMID- 8520210 TI - Determination of D-amino acids, derivatized with 4-fluoro-7-nitro-2,1,3 benzoxadiazole (NBD-F), in wine samples by high-performance liquid chromatography. AB - The concentrations of D-amino acids and their enantiomeric ratios in wind samples were determined by high-performance liquid chromatography with fluorometric detection. We used Pirkle type chiral stationary phases and fluorogenic reagent, 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) for simplicity and high sensitivity. The amino acids determined were D-enantiomers of alanine (Ala), aspartic acid, glutamic acid, isoleucine (Ile) and leucine (Leu), D-Asparagine, glutamine and -lysine were not detected. D-Leu was detected in red and rose wine samples, and D-Ile was determined only in rose wine. In contrast, neither D-Leu nor Ile were detected in white wine samples. The concentration of D-Ala was the most prominent among these amino acids with the highest content of approximately 180 microns (D/D + L ratio; 25%) in rose wine. PMID- 8520211 TI - Availability of phenylisothiocyanate for the amino acid sequence/configuration determination of peptides containing D/L-amino acids. AB - A potential use for phenylisothiocyanate (PITC), the most popular Edman reagent, is presented for analysis of the amino acid sequence and configuration in peptides containing D/L-amino acids. After derivatization with PITC of the N terminal amino acid (L-Tyr) of an enkephalin analogue, [D-Ala2, D-Leu5] enkephalin, followed by cleavage/cyclization with trifluoroacetic acid at 50 degrees C for 5 min, the liberated 2-anilino-5-thiazolinone-L-Tyr (ATZ-L-Tyr) was further treated with 20% aqueous trifluoroacetic acid at 50 degrees C for 10 min. The resultant phenylthiohydantoin (PTH)-L-Tyr was then separated on a chiral stationary phase (a penylcarbamoylated cyclodextrin column), retaining its configuration. The residual sequence and configurations of the peptide (D-Ala-Gly L-Phe-D-Leu) were also determined by separating the corresponding PTH-D- or L amino acids on chiral columns. This method may be applicable to an automatic Edman sequence analyzer for the configuration determination of peptides containing D/L-amino acids. PMID- 8520212 TI - Influence of intense sound stimuli on skin microcirculation. AB - Sound influences not only the organ of hearing but also other systems including the circulation. The purpose of the present study was to investigate the effect of strong sound on the skin microcirculation of the palmar area of the hand and of the plantar area of the foot, which are areas of dense microvasculature and rich sympathetic innervation. The laser Doppler technique was used for measuring cutaneous red cell flux (RCF). Eighteen normal subjects were studied. The results indicate that a pure tone sound of 1500 Hz, with an intensity of 100 dBA and duration 5 s, applied by earphones caused a significant decrease in RCF in 14 out of 18 subjects in the finger but not in the foot skin. A higher intensity (110 dBA) tone caused a stronger decrease of RCF in the finger. The latency and the duration of the reaction showed a dependence on the intensity of the sound, i.e. the reaction to the stronger stimulus was of shorter latency (p < 0.01) and longer duration (p < 0.05). The duration of the reaction did not show significant change when a longer stimulus of 30 s was applied. Repetitive stimuli evoked habituation (p < 0.05). PMID- 8520214 TI - Central sympathetic dysregulation and immunological abnormalities in a case of progressive facial hemiatrophy (Parry-Romberg disease). AB - A case of hemifacial atrophy (Parry-Romberg disease) is discussed. Electrophysiological and immunological studies were performed. Electromyography, blink reflex and trigeminal evoked potential abnormalities indicate that the brain stem may be implicated in the aetiology of the disease. Immunological evidence favoured this possibility and demonstrated possible involvement of the noradrenergic system. Hyperactivity of the brain stem sympathetic centres, possibly caused by an autoimmune process, may be the primary cause of the cutaneous and subcutaneous atrophy in Parry-Romberg disease. PMID- 8520213 TI - Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus. AB - Vascular smooth muscle contractile responses to neuropeptide Y, alpha,beta methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endothelium in vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1-1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or alpha,beta-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 +/- 14.0%, p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 +/- 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus. PMID- 8520215 TI - Sympathetic skin response in patients with reflex sympathetic dystrophy. AB - The sympathetic skin response (SSR) originates from synchronized activation of the sweat glands as a response to a volley discharge in efferent sympathetic nerve fibres. The aim of the study was to verify the diagnostic value of SSR in patients with reflex sympathetic dystrophy (RSD). SSR was recorded in 20 normal subjects and in 24 patients with predominantly chronic RSD. In normal subjects inter- and intra-individually different mono-, bi- and triphasic potentials could be recorded without difference of the waveform from side to side. SSR abnormalities were found in 15 patients and correlated with the severity of the disease. In patients with slight dystrophies, SSR was predominantly normal. In intermediate dystrophies, mainly differences of the SSR waveform between sides could be recorded, indicating unilateral sudomotor dysfunction. In severe dystrophies abnormalities of SSR amplitude or latency were found, indicating more serious disturbance of sudomotor activity, possibly due to a lesion of sympathetic fibres. The SSR provides useful information on sudomotor dysfunction in patients with RSD. However, as there is no consensus in the literature for the clinical criteria to diagnose RSD, it is not yet possible to determine the final diagnostic value of SSR for the diagnoses of RSD. PMID- 8520216 TI - Effect of recombinant erythropoietin on anemia and orthostatic hypotension in primary autonomic failure. AB - Anemia is a common complication of autonomic failure and reduced red blood cell mass may contribute to the orthostatic hypotension of these patients. We investigated whether treatment with recombinant erythropoietin improves anemia and increases blood pressure in patients with primary autonomic failure. Three patients with multiple system atrophy and autonomic failure and one with pure autonomic failure were studied. All patients had normocytic normochromic anemia and low (n = 2) or normal (n = 2) serum levels of erythropoietin. Treatment with erythropoietin, 4000 U subcutaneously biweekly for 6 weeks, increased hematocrit and blood pressure in all patients. Hematocrit increased from 33.9 +/- 0.7 to 44.3 +/- 1.4%, blood pressure in supine position increased from 150 +/- 8/87 +/- 8 (systolic/diastolic; mean +/- SD) to 166 +/- 25/92 +/- 12 mmHg, and after 3 min in the head-up tilt position from 86 +/- 21/47 +/- 15 to 102 +/- 23/63 +/- 12 mmHg, (p < 0.05). All patients reported improvement in orthostatic symptoms and increased tolerance to standing. The study shows that treatment with erythropoietin improves anemia, increases blood pressure and ameliorates orthostatic hypotension in patients with primary autonomic failure. PMID- 8520217 TI - Sympathetic skin response in Guillain-Barre syndrome. AB - Dysautonomia is a common feature of Guillain-Barre (GB) syndrome and is sometimes the cause of significant morbidity and death. Changes in sympathetic skin response (SSR) may be one of the accompaniments of dysautonomia. An attempt was made to correlate SSR changes with clinical and electrophysiologic features in a group of 24 patients with GB syndrome fulfilling NINDS (National Institute of Neurological Disorders and Stroke) criteria. A total of nine patients had absent SSR. Thirteen patients had clinical dysautonomia, of whom five had absent SSR. Five patients had features of predominant axonal damage and preserved SSR. A trend towards correlation of SSR abnormalities with common peroneal nerve conduction parameters (velocity and compound muscle action potential amplitude) was noted. We conclude that SSR abnormalities are common in GB syndrome and may be complementary to bed-side tests for autonomic dysfunction. PMID- 8520218 TI - 1H, 15N, 13C and 13CO assignments and secondary structure determination of basic fibroblast growth factor using 3D heteronuclear NMR spectroscopy. AB - The assignments of the 1H, 15N, 13CO and 13C resonances of recombinant human basic fibroblast growth factor (FGF-2), a protein comprising of 154 residues and with a molecular mass of 17.2 kDa, is presented based on a series of three dimensional triple-resonance heteronuclear NMR experiments. These studies employ uniformly labeled 15N- and 15N-/13C-labeled FGF-2 with an isotope incorporation > 95% for the protein expressed in E. coli. The sequence-specific backbone assignments were based primarily on the interresidue correlation of C alpha, C beta and H alpha to the backbone amide 1H and 15N of the next residue in the CBCA(CO)NH and HBHA(CO)NH experiments and the intraresidue correlation of C alpha, C beta and H alpha to the backbone amide 1H and 15N in the CBCANH and HNHA experiments. In addition, C alpha and C beta chemical shift assignments were used to determine amino acid types. Sequential assignments were verified from carbonyl correlations observed in the HNCO and HCACO experiments and C alpha correlations from the HNCA experiment. Aliphatic side-chain spin systems were assigned primarily from H(CCO)NH and C(CO)NH experiments that correlate all the aliphatic 1H and 13C resonances of a given residue with the amide resonance of the next residue. Additional side-chain assignments were made from HCCH-COSY and HCCH TOCSY experiments. The secondary structure of FGF-2 is based on NOE data involving the NH, H alpha and H beta protons as well as 3JHNH alpha coupling constants, amide exchange and 13C alpha and 13C beta secondary chemical shifts. It is shown that FGF-2 consists of 11 well-defined antiparallel beta-sheets (residues 30-34, 39-44, 48-53, 62-67, 71-76, 81-85, 91-94, 103-108, 113-118, 123 125 and 148-152) and a helix-like structure (residues 131-136), which are connected primarily by tight turns. This structure differs from the refined X-ray crystal structures of FGF-2, where residues 131-136 were defined as beta-strand XI. The discovery of the helix-like region in the primary heparin-binding site (residues 128-138) instead of the beta-strand conformation described in the X-ray structures may have important implications in understanding the nature of heparin FGF-2 interactions. In addition, two distinct conformations exist in solution for the N-terminal residues 9-28. This is consistent with the X-ray structures of FGF 2, where the first 17-19 residues were ill defined. PMID- 8520219 TI - Overexpression of myoglobin and assignment of its amide, C alpha and C beta resonances. AB - Sperm whale apomyoglobin was expressed to high levels on minimal media and isotopically labeled with 13C and 15N nuclei. The isotopically labeled apoprotein was purified to homogeneity in a single step by reversed-phase chromatography and reconstituted with hemin and carbon monoxide gas for NMR analysis. Sequence specific backbone 1HN, 15N and 13C alpha as well as side-chain 13C beta resonance assignments have been made for over 90% of the amino acids in the carbon monoxide complex of the protein. Resonance assignments were made by analysis of a series of 3D triple resonance spectra measured on the uniformly labeled sample. These assignments will provide the basis for analyzing the effects of point site mutations on the structure, stability and dynamics of the protein in solution. PMID- 8520220 TI - NMRPipe: a multidimensional spectral processing system based on UNIX pipes. AB - The NMRPipe system is a UNIX software environment of processing, graphics, and analysis tools designed to meet current routine and research-oriented multidimensional processing requirements, and to anticipate and accommodate future demands and developments. The system is based on UNIX pipes, which allow programs running simultaneously to exchange streams of data under user control. In an NMRPipe processing scheme, a stream of spectral data flows through a pipeline of processing programs, each of which performs one component of the overall scheme, such as Fourier transformation or linear prediction. Complete multidimensional processing schemes are constructed as simple UNIX shell scripts. The processing modules themselves maintain and exploit accurate records of data sizes, detection modes, and calibration information in all dimensions, so that schemes can be constructed without the need to explicitly define or anticipate data sizes or storage details of real and imaginary channels during processing. The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks. PMID- 8520221 TI - Determination of the NMR solution structure of a specific DNA complex of the Myb DNA-binding domain. AB - The solution structure of a specific DNA complex of the minimum DNA-binding domain of the mouse c-Myb protein was determined by distance geometry calculations using a set of 1732 nuclear Overhauser enhancement (NOE) distance restraints. In order to determine the complex structure independent of the initial guess, we have developed two different procedures for the docking calculation using simulated annealing in four-dimensional space (4D-SA). One is a multiple-step procedure, where the protein and the DNA were first constructed independently by 4D-SA using only the individual intramolecular NOE distance restraints. Here, the initial structure of the protein was a random coil and that of the DNA was a typical B-form duplex. Then, as the starting structure for the next docking procedure, the converged protein and DNA structures were placed in random molecular orientations, separated by 50 A. The two molecules were docked by 4D-SA utilizing all the restraints, including the additional 66 intermolecular distance restraints. The second procedure comprised a single step, in which a random-cell protein and a typical B-form DNA duplex were first placed 70 A from each other. Then, using all the intramolecular and intermolecular NOE distance restraints, the complex structure was constructed by 4D-SA. Both procedures yielded the converged complex structures with similar quality and structural divergence, but the multiple-step procedure has much better convergence power than the single-step procedure. A model study of the two procedures was performed to confirm the structural quality, depending upon the number of intermolecular distance restraints, using the X-ray structure of the engrailed homeodomain-DNA complex. PMID- 8520222 TI - Measurement of intrinsic exchange rates of amide protons in a 15N-labeled peptide. AB - We have used a modified version of a previously proposed technique, MEXICO [Gemmecker et al. (1993) J. Am. Chem. Soc., 115, 11620], and improved data analysis procedures in order to measure rapid hydrogen exchange (HX) rates of amide protons in peptides labeled only with 15N. The requirement of 13C-/15N labeled material has been circumvented by adjusting conditions so that NOE effects associated with amide protons can be neglected (i.e., omega 0 tau c approximately 1). The technique was applied to an unstructured 15N-labeled 12 residue peptide to measure intrinsic HX rates, which are the essential reference for examining protein and peptide structure and dynamics through deceleration of HX rates. The method provided accurate HX rates from 0.5 to 50 s-1 under the conditions used. The measured rates were in good agreement with those predicted using correction factors determined by Englander and co-workers [Bai et al. (1993) Proteins, 17, 75], with the largest deviations from the predicted rates found for residues close to the N-terminus. The exchange rates were found to exhibit significant sensitivity to the concentration of salt in the sample. PMID- 8520223 TI - Measuring protein self-association using pulsed-field-gradient NMR spectroscopy: application to myosin light chain 2. AB - At the millimolar concentrations required for structural studies, NMR spectra of the calcium-binding protein myosin light chain 2 (MLC2) showed resonance line widths indicative of extensive self-association. Pulsed-field-gradient (PFG) NMR spectroscopy was used to examine whether MLC2 aggregation could be prevented by the zwitterionic bile salt derivative 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonate (CHAPS). PFG NMR measurements indicated that CHAPS was capable of preventing MLC2 self-association, but only at concentrations well above the critical micelle concentration of approximately 7.5 mM. CHAPS was most effective at a concentration of 22.5 mM, where the apparent molecular mass of MLC2 corresponded to a protein monomer plus seven molecules of bound detergent. The resolution and sensitivity of 2D 15N-1H HSQC spectra of MLC2 were markedly improved by the addition of 25 mM CHAPS, consistent with a reduction in aggregation following addition of the detergent. The average amide nitrogen T2 value for MLC2 increased from approximately 30 ms in the absence of CHAPS to approximately 56 ms in the presence of 25 mM CHAPS. The results of this study lead us to propose that PFG NMR spectroscopy can be used as a facile alternative to conventional techniques such as analytical ultracentrifugation for examining the self-association of biological macromolecules. PMID- 8520224 TI - Three-dimensional solid-state NMR spectroscopy of a peptide oriented in membrane bilayers. AB - A three-dimensional 1H chemical shift/1H-15N dipolar coupling/15N chemical shift correlation spectrum was obtained on a sample of specifically 15N-labeled magainin peptides oriented in lipid bilayers between glass plates in a flat-coil probe. The spectrum showed complete resolution of the resonances from two labeled amide sites in all three dimensions. The three orientationally dependent frequencies associated with each resonance enabled the orientation of the peptide planes to be determined relative to the direction of the applied magnetic field. These results demonstrate the feasibility of multiple-pulse spectroscopy in a flat-coil probe, the ability to measure three spectral parameters from each site in a single experiment, and the potential for resolving among many labeled sites in oriented membrane proteins. PMID- 8520225 TI - Spin-locked multiple quantum coherence for signal enhancement in heteronuclear multidimensional NMR experiments. AB - For methine sites the relaxation rate of 13C-1H two-spin coherence is generally slower than the relaxation rate of the individual 13C and 1H single spin coherences. The slower decay of two-spin coherence can be used to increase the sensitivity and resolution in heteronuclear experiments, particularly those that require correlation of H alpha and C alpha chemical shifts. To avoid dephasing of the two-spin coherence caused by 1H-1H J-couplings, the 1H spin is locked by the application of a weak rf field, resulting in a spin-locked multiple quantum coherence. For a sample of calcium-free calmodulin, use of the multiple quantum approach yields significant signal enhancement over the conventional constant time 2D HSQC experiment. The approach is applicable to many multidimensional NMR experiments, as demonstrated for a 3D 13C-separated ROESY CT-HMQC spectrum. PMID- 8520226 TI - Going political. Family physicians can promote child health in Canada. PMID- 8520227 TI - Doctors, nurses, and primary care. PMID- 8520228 TI - Unpublishable research. PMID- 8520229 TI - Tuberculosis. A widespread health issue. PMID- 8520230 TI - Special approach to rural medicine training. PMID- 8520231 TI - Try it; you'll like it. PMID- 8520232 TI - Comparing obstetric practice patterns. PMID- 8520233 TI - Chickenpox during pregnancy. Small but real risk. PMID- 8520234 TI - Dilemmas in care of the elderly. PMID- 8520235 TI - Dermacase. Erysipeloid. PMID- 8520236 TI - The feisty family. PMID- 8520237 TI - Individuals with a chemical-dependent family member. Does their health care use increase? AB - OBJECTIVE: To examine health care utilization patterns of individuals who have a chemical-dependent family member (parent, spouse, or child). DESIGN: Morbidity and health care utilization patterns were examined for a 12-month period using the claims administrative data from the Alberta Health Care Insurance Plan (AHCIP). SETTING: General medical practice specializing in the treatment of addiction disorders. PARTICIPANTS: Two hundred seventy-eight (73 male, 205 female) subjects were identified between 1987 and 1990. No members of the subject group were Natives, and none were dependent on chemicals during the study period. A control group, matched for age, sex, and family size, was randomly selected from AHCIP records. MAIN OUTCOME MEASURES: Number and type of health care services and diagnoses listed in health care claims classified using the International Classification of Diseases. RESULTS: In 91% of cases, the chemical dependent family member was male. Members of the subject group presented more often with mental disorders, digestive system problems, obstetrical problems, injuries, and poorly defined conditions. Also, they were more likely to have nonreferred visits, to have specialist visits, and to use laboratory services than population-matched controls. The subject group's use of specialists and laboratory services amounted to twice the cost of the control group's use of these services. CONCLUSIONS: Results show that individuals who have a chemical dependent family member use more health care services than the general population. Morbidity among the subject group appears to be similar to that among chemical-dependent individuals; diagnoses related to stress and trauma are common. PMID- 8520238 TI - Comparative yield of endocervical and metaplastic cells. Two sampling techniques: wooden spatula and cytology brush. AB - OBJECTIVE: To compare two sampling techniques in their ability to obtain endocervical and metaplastic cells from the Papanicolaou smear. DESIGN: Prospective clinical trial comparing the criterion standard of a wooden spatula to a cytology brush. SETTING: Community-based family medicine clinic in London, Ont. PATIENTS: Consecutive sample of 102 women aged 15 to 58 years requiring a Pap smear between October 1992 and October 1993 who presented to the office of their family physician and were assessed by one resident or one faculty physician. INTERVENTIONS: A Pap smear was obtained from each participant using first the wooden spatula and then the cytology brush. MAIN OUTCOME MEASURES: The number of Pap smears done in the study population that contained endocervical or metaplastic cells. RESULTS: Endocervical cell yield was significantly greater using the cytology brush (93.1%) than using the spatula (61.8%) (P < 0.001). There was no significant difference in metaplastic cell yield between the cytology brush (71.6%) and the spatula (63.7%). At least one of these cell types was identified on 95.1% of cytology brush samples and on 79.4% of spatula samples (P < 0.001). The resident and faculty physician were not significantly different in their rate of detecting endocervical or metaplastic cells. CONCLUSIONS: Adding a cytology brush sample to the Pap smear resulted in a significant increase in the rate of Pap smears that detected cells. The cytology brush was significantly better than the spatula for detecting endocervical cells (P < 0.001), but not significantly better for detecting metaplastic cells. PMID- 8520239 TI - Innocent heart murmurs in children. Taking a diagnostic approach. AB - Nearly all pediatric murmurs are heard in normal hearts and are not due to cardiac disorders. These murmurs usually can be classified by distinctive features and distinguished from organic murmurs by skillful clinical examination. This article reviews the various types of innocent heart murmurs in children, discusses their differential diagnoses, and suggests an approach to sorting out pediatric murmurs. PMID- 8520240 TI - Preventing children from smoking. How family physicians and pediatricians can help. AB - Children progress through five stages to become smokers: anticipation, initiation, experimentation, habituation, and adult smoking. Children at risk of smoking can be identified. Physicians should ask for information that predicts smoking behaviour, advise not starting, assist staying a nonsmoker, arrange follow-up visits and booster sessions, and anticipate challenges to antismoking behaviours. PMID- 8520242 TI - A dying child. AB - Dying children have special needs related to their age and stage of development. Family physicians are sometimes asked to care for children at home or in hospital in the final days of life. Working with families and other caregivers, family physicians are well placed to care for dying children. PMID- 8520241 TI - Preventing adolescent pregnancy and associated risks. AB - Adolescent pregnancy is a complex and frustrating problem that exacts a large social and personal cost. This year approximately 40,000 Canadian teenagers will become pregnant. With proper prevention, this number could be reduced. Pregnant teenagers seem to be at increased risk for some obstetric complications and their children for some neonatal complications. Family physicians who see patients over the course of a lifetime are in a good position to prevent adolescent pregnancy and the associated complications. PMID- 8520243 TI - Effective interventions for nearly drowned children. AB - Near-drowning, one of the great tragedies in emergency pediatrics, is largely preventable. It generates particular concern and frustration among those who must treat its victims and their families. Should every drowned child be resuscitated? What treatment will minimize the risk of secondary brain injury? PMID- 8520244 TI - Health reform and family physicians' skills. PMID- 8520245 TI - Comparing reactions to two DPT vaccines. PMID- 8520246 TI - Serum gentamicin levels: a comparison between the Syva Solaris and the Syva QST analysers. AB - Enzyme-multiplied immunoassay techniques (EMIT) are now widely used as an effective method for monitoring gentamicin concentrations to ensure adequate serum levels. The current EMIT system was to be superseded by an improved version and both were run in parallel over a nine-month period and the results compared. During this time the systems were evaluated for ease of use, and reproducibility of results. The newer, EMIT produced more consistent calibration results with less kit-to-kit variation, which in turn gave more reproducible results both with patients' sera and the monthly NEQAS quality controls. The newer system was put into routine use at the end of the trial. PMID- 8520247 TI - Spontaneous loss of HBeAg and development of anti-HBe during long-term follow-up of blood donors found to be HBsAg-positive. AB - Since 1980, at North London Blood Transfusion Centre 61 (14%) of a total of 442 hepatitis B surface antigen (HBsAg) positive carriers have been hepatitis B e antigen (HBeAg) positive by radioimmunoassay at the time of detection, with 353 (80%) anti-HBe positive. We have undertaken long-term follow-up of infectivity markers in 285 of these 442 HBsAg carriers detected by routine screening. Donors undergoing acute HBV infection were excluded from the analysis. The donor follow up times ranged from 1.2 to 13.5 years. Regular follow-up samples were obtained and examined for HBsAg, HBeAg, anti-HBe, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Thirty-five (12.3%) of the 285 carriers were HBeAg-positive when first detected. Eight of these 35 developed anti-HBe during follow-up. At no time did any carrier revert from anti-HBe to HBeAg. When these data were subjected to a Kaplan--Meier analysis an estimated lower quartile time to seroconversion of 3.83 years, and a median seroconversion time of 8.25 years were predicted. This corresponds to a mean rate of 6.5% per annum for the first 25% to seroconvert, and 5.7 for the next 25%. PMID- 8520248 TI - Folate requirements for health in different population groups. AB - Folate coenzymes are required for the transfer and utilisation of one-carbon units in essential reactions involving amino acid metabolism, and the synthesis of purines and pyrimidines. Much of our understanding of human folate requirement comes from the study of folate deficiency, as it progresses from early haematological changes to eventual clinical manifestations. In population studies folate status may be assessed during the early stages of negative balance, before functional and clinical changes occur, by means of both dietary evaluation and biochemical measurements. Sub-optimal folate status may arise as a result of a number of environmental, physiological or pathological factors which cause decreased availability, increased requirement, or both. Current reference values for folate apply to intakes in healthy population groups. New recommendations for folic acid in the prevention of both first occurrence and recurrence of neural tube defects have recently been published. Folate nutrition may also have a role in coronary heart disease and various cancers. PMID- 8520249 TI - Screening for cancer and pre-cancer. AB - In some countries cervical screening has been established for many years and has had a considerable impact on mortality from invasive cervical cancer. Because of this success, and in view of the continued high incidence and mortality from cancers generally, there is much interest in extending screening for other types of cancer. One example is the more recent introduction of mammographic breast screening in the UK. For other cancers, such as those of the colon, rectum, prostate and ovary, screening is currently confined to demonstration projects. Much of the success of cervical screening is attributable to the fact that abnormalities are detectable at a pre-cancerous stage, and treatment is effective in halting progression to invasive cancer. This is not always the case for most other forms of cancer screening. PMID- 8520250 TI - The immunoregulatory roles of transforming growth factor beta. AB - Transforming growth factor-beta is a 25 kD polypeptide produced by both healthy and neoplastic cells. This cytokine effects the introduction of immune response, but its exact mechanism remains to be elucidated. In this paper the immuno regulatory role of this cytokine on both the immunocompetent cells and accessory molecules is discussed. The growth factor-induced up and down regulation of the immune response suggest that transforming growth factor-beta can done some extent modulate certain pathological conditions, and hence suppressed production of this growth factor has potential benefits for bimodal immunotherapy. PMID- 8520251 TI - Phagocytic NADPH oxidase and its role in chronic granulomatous disease. AB - Chronic granulomatous disease is an inherited disease manifest as recurrent bacterial and fungal infections. Although extremely rare, in the absence of long term treatment it can be lead to death at an early age. Even though the disease was first described almost 40 years ago it is only recently that the enzymatic defects which cause the disease have been well characterised, allowing an instructive classification of the disorder and paving the way for advances in gene therapy as a lasting cure. PMID- 8520252 TI - Pathogenesis of bacterial infections of the respiratory tract. AB - The main function of the lung is gas exchange, which means that the respiratory mucosa is constantly exposed to noxious substances and potentially infective agents inhaled from the environment. Despite this, in health the number of bacteria in the upper respiratory tract (nose and pernasal tissue) is low and the lower (bronchopulmonary) respiratory tract is sterile. However, respiratory tract infections are common in humans, either due to malfunction of a complex array of defence mechanisms or because of the virulence of a particular microorganism. The pathogenesis of these infections is discussed. PMID- 8520253 TI - Picro-thionin (Schmorl) staining of bone and other hard tissues. AB - A much simplified method for the demonstration of bone morphology using Schmorl's picro-thionin technique is described, and the necessity for reliable samples of thionin emphasised. Findings from previous experiments provide the evidence and theoretical background to justify the use of certified stains for this purpose. PMID- 8520254 TI - Erroneous automated eosinophil counts in HIV-infected individuals. PMID- 8520255 TI - Gonococcal serovar patterns in Glasgow: 1990-1992. AB - Using monoclonal antibodies directed against protein 1 (major outer membrane protein) in the cell wall of Neisseria gonorrhoeae it is possible to serotype the gonococcus into different sub-groups. This study was designed to analyse the distribution of such serovars in Glasgow, Scotland, and report associations between serovars and clinical features of infection. N. gonorrhoeae isolated from all patients with a diagnosis of gonorrhoea attending genitourinary medicine clinics in Glasgow were serotyped between January 1990 and December 1992. The results were then correlated with sexual orientation of patients, penicillin sensitivity, site of infection, location of acquisition of infection and presence of symptoms. Six hundred and four episodes of gonococcal infection were analysed and an association between certain serovars with sexual orientation, penicillin sensitivity and asymptomatic infection was found. No association between serovar type and locality of acquisition of infection was apparent. Although there was a decreasing trend in the incidence of gonorrhoea overall, infections in homosexual men increased over the three-year study period. The associations between serovars and other features of gonococcal infection are discussed. The observed increase in homosexually-acquired infection has implications with regard to the spread of human immunodeficiency virus infection in this area, and suggests that attempts to promote safer sex in this group are failing. PMID- 8520256 TI - Routine detection of Trichomonas vaginalis in genital specimens using culture in microtitre trays. AB - The culture of genital specimens for the detection of Trichomonas vaginalis is generally regarded as the most sensitive technique available for routine use. However, the technique is relatively expensive and time-consuming, involving the preparation of one or more wet mounts from the culture to observe motile trichomonads. Considerable savings in cost and time can be achieved by using culture in microtitre trays and visualisation with an inverted microscope. PMID- 8520257 TI - Oestradiol measurement in women on oral hormone replacement therapy: the validity of commercial test kits. AB - Four commercially available methods for the measurement of oestradiol were used to assay oestradiol concentrations in samples from women receiving oral hormone replacement therapy. Significant differences in results were found between samples that were measured direct and those subjected to an extraction procedure. There was considerable variability in the extraction: direct ratio between methods, indicating that with some methods an extraction procedure should be performed before analysis on samples from women receiving oral hormone replacement therapy. Factors that account for discrepant results between methods probably include increased concentration of sex hormone binding globulin together with cross-reacting metabolites and conjugates. PMID- 8520258 TI - Deaths of children in house fires. PMID- 8520259 TI - Randomised controlled trials in general practice. PMID- 8520260 TI - Reforming England's blood transfusion service. PMID- 8520261 TI - Violence involving children. PMID- 8520262 TI - Harsh Russian winter takes an early toll. PMID- 8520264 TI - France faces radical health insurance reforms. PMID- 8520263 TI - Indian doctors may be tried in consumer courts. PMID- 8520265 TI - US midwives have low caesarean rate. PMID- 8520266 TI - Counting the cost of alcohol for young people. PMID- 8520267 TI - US woman wins compensation in breast implant case. PMID- 8520268 TI - Quebec faces hospital closures to balance books. PMID- 8520270 TI - Pregnant women receiving benefit in Britain eat badly. PMID- 8520269 TI - Move to reform GPs' committee fails. PMID- 8520271 TI - Sydney's asthma witch hunt. PMID- 8520272 TI - Changes in incidence of and mortality from breast cancer in England and Wales since introduction of screening. United Kingdom Association of Cancer Registries. AB - OBJECTIVE: To assess the impact of the NHS breast screening programme on the incidence of and mortality from breast cancer. DESIGN: Comparison of age specific incidence and mortality before and after the introduction of screening in the late 1980s. SETTING: England and Wales. SUBJECTS: Women aged over 30 years. RESULTS: In 1992 the age standardised incidence of breast cancer was 40% higher than in 1979. After the introduction of screening in 1988 recorded incidence rates rose steeply in the screened age group (50-64 year olds) but not in others. In 1992 the rates levelled off at about 25% higher than in 1987. Total mortality from breast cancer has increased steadily since the 1950s; the rates increased earlier in the younger age groups. By the mid-1980s rates had begun to fall in the younger age groups; but total mortality was still among the highest in the world. Age standardised mortality in the 55-69 age group changed little during the first three years of screening but then fell steeply and in 1994 was 12% lower than in 1987. CONCLUSIONS: Since the introduction of screening there have been pronounced increases in recorded incidence in the screened age group. Cancer registries have an essential role in assessing screening programmes and cancer services. The steep decrease in mortality in 55-69 year olds which began three years after screening started is unlikely to be due to screening. The widespread adoption of treatment with tamoxifen during this period may be important. With the reduction in mortality already observed and the expected additional benefits from screening, the Health of the Nation target should be achieved. PMID- 8520273 TI - Patients who reattend after head injury: a high risk group. AB - OBJECTIVE: To assess risk factors for important neurosurgical effects in patients who reattend after head injury. DESIGN: Retrospective study. SUBJECTS: 606 patients who reattended a trauma unit after minor head injury. MAIN OUTCOME MEASURES: Intracranial abnormality detected on computed tomography or the need for neurosurgical intervention. RESULTS: Five patients died: two from unrelated causes and three from raised intracranial pressure. On multiple regression analysis the only significant predictor for both abnormality on computed tomography (14.4% of reattenders) and the need for operation (5% of reattenders) was vault fracture seen on the skull radiograph (P < 10(-6)); predictors for abnormal computed tomogram were a Glasgow coma scale score < 15 at either first or second attendance (P < 0.0001) and convulsion at second attendance (P < 0.05); predictive for operation only was penetrating injury of the skull (P < 10(-6)). On contingency table analysis these associations were confirmed. In addition significant associations with both abnormality on computed tomography and operation were focal neurological abnormality, weakness, or speech disturbance. Amnesia or loss of consciousness at the time of initial injury, personality change, and seizures were significantly associated only with abnormality on computed tomography. Headache, dizziness, nausea, and vomiting were common in reattenders but were found to have no independent significance. CONCLUSIONS: All patients who reattend after head injury should undergo computed tomography as at least 14% of scans can be expected to yield positive results. Where this facility is not available patients with predictors for operation should be urgently referred for neurosurgical opinion. Other patients can be readmitted and need referral only if symptoms persist despite symptomatic treatment or there is neurological deterioration while under observation. These patients are a high risk group and should be treated seriously. PMID- 8520274 TI - Utilisation of hormone replacement therapy by women doctors. AB - OBJECTIVES: To ascertain the prevalence and duration of use of hormone replacement therapy by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: General practices in the United Kingdom. SUBJECTS: Randomised stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current principal list of the Medical Register. MAIN OUTCOME MEASURES: Prevalence and duration of use of hormone replacement therapy; menopausal status. RESULTS: Overall, 45.7% (436/954) of women doctors aged between 45 and 65 years had ever used hormone replacement therapy. When the results from women still menstruating regularly were excluded, 55.2% (428) were ever users and 41.2% (319) current users. The cumulative probability of remaining on hormone replacement therapy was 0.707 at five years and 0.576 at 10 years. CONCLUSIONS: Women doctors have a higher prevalence of use of hormone replacement therapy than has been reported for other women in the United Kingdom, and most users seem to be taking hormone replacement therapy for more than five years. The results may become generalisable to the wider population as information on the potential benefits of hormone replacement therapy is disseminated. PMID- 8520275 TI - Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. AB - OBJECTIVE: To determine the frequency of cardiovascular risk factors in people categorised by previously defined "action levels" of waist circumference. DESIGN: Prevalence study in a random population sample. SETTING: Netherlands. SUBJECTS: 2183 men and 2698 women aged 20-59 years selected at random from the civil registry of Amsterdam and Maastricht. MAIN OUTCOME MEASURES: Waist circumference, waist to hip ratio, body mass index (weight (kg)/height (m2)), total plasma cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, age, and lifestyle. RESULTS: A waist circumference exceeding 94 cm in men and 80 cm in women correctly identified subjects with body mass index of > or = 25 and waist to hip ratios > or = 0.95 in men and > or = 0.80 in women with a sensitivity and specificity of > or = 96%. Men and women with at least one cardiovascular risk factor (total cholesterol > or = 6.5 mmol/l, high density lipoprotein cholesterol < or = 0.9 mmol/l, systolic blood pressure > or = 160 mm Hg, diastolic blood pressure > or = 95 mm Hg) were identified with sensitivities of 57% and 67% and specificities of 72% and 62% respectively. Compared with those with waist measurements below action levels, age and lifestyle adjusted odds ratios for having at least one risk factor were 2.2 (95% confidence interval 1.8 to 2.8) in men with a waist measurement of 94-102 cm and 1.6 (1.3 to 2.1) in women with a waist measurement of 80-88 cm. In men and women with larger waist measurements these age and lifestyle adjusted odds ratios were 4.6 (3.5 to 6.0) and 2.6 (2.0 to 3.2) respectively. CONCLUSIONS: Larger waist circumference identifies people at increased cardiovascular risks. PMID- 8520276 TI - Increased serum concentration of von Willebrand factor in non-insulin dependent diabetic patients with and without diabetic nephropathy. PMID- 8520277 TI - Risk of otitis externa after swimming in recreational fresh water lakes containing Pseudomonas aeruginosa. AB - OBJECTIVE: To determine whether an outbreak of otitis externa was due to bathing in recreational fresh water lakes and to establish whether the outbreak was caused by Pseudomonas aeruginosa in the water. DESIGN: Matched case-control study. SETTING: The Achterhoek area, the Netherlands. SUBJECTS: 98 cases with otitis externa and 149 controls matched for age, sex, and place of residence. MAIN OUTCOME MEASURES: Odds ratios for type of swimming water and frequency of swimming; presence of P aeruginosa in ear swabs and fresh water lakes. RESULTS: Otitis externa was strongly associated with swimming in recreational fresh water lakes in the previous two weeks (odds ratio 15.5 (95% confidence interval) 4.9 to 49.2) compared with non-swimming). The risk increased with the number of days of swimming, and subjects with recurrent ear disease had a greatly increased risk. The lakes met the Dutch bathing water standards and those set by the European Commission for faecal pollution in the summer of 1994, but P aeruginosa was isolated from all of them, as well as from the ear swabs of 78 (83%) of the cases and 3 (4%) of the controls. CONCLUSIONS: Even when current bathing water standards are met, swimming can be associated with a substantial risk of otitis externa because of exposure to P aeruginosa. People with recurrent ear disease should take special care when swimming in waters containing P aeruginosa. PMID- 8520278 TI - Diagnosis and treatment of nasal polyps. PMID- 8520279 TI - Creutzfeldt-Jakob disease and bovine spongiform encephalopathy: any connection? PMID- 8520280 TI - Introducing the Internet. AB - The benefits to medical practitioners of using the Internet are growing rapidly as the Internet becomes easier to use and ever more biomedical resources become available on line. The Internet is the largest computer network in the world; it is also a virtual community, larger than many nation states, with its own rules of behaviour or "netiquette." There are several types of Internet connection and various ways of acquiring a connection. Once connected, you can obtain, free of charge, programs that allow easy use of the Internet's resources and help on how to use these resources; you can access many of these resources through the hypertext references in the on line version of this series (go to http:@www.bmj.com/bmj/ to reach the electronic version). You can then explore the various methods for accessing, manipulating, or disseminating data on the Internet, such as electronic mail, telnet, file transfer protocol, and the world wide web. Results from a search of the world wide web for information on the rare condition of Recklinghausen's neurofibromatosis illustrate the breadth of medical information available on the Internet. PMID- 8520281 TI - ABC of atrial fibrillation. Aetiology, pathophysiology, and clinical features. PMID- 8520282 TI - Managing cleft lip and palate. Editorial proves controversial. PMID- 8520283 TI - Managing cleft lip and palate. Trials of management are inevitably long. PMID- 8520284 TI - Managing cleft lip and palate. Specialised multidisciplinary team can solve problems of distance. PMID- 8520285 TI - Managing cleft lip and palate. Language outcomes are important. PMID- 8520286 TI - Managing cleft lip and palate. An invitation for Markus to present his results. PMID- 8520287 TI - Amphetamine misuse in southern Italy. PMID- 8520288 TI - Deputising general practitioners' role in emergencies. GPs do not have a monopoly on supporting the bereaved. PMID- 8520289 TI - Deputising general practitioners' role in emergencies. Lessons for both doctors involved. PMID- 8520290 TI - Prefer diazepam for initial control of pre-eclamptic fits. PMID- 8520291 TI - Deputising general practitioners' role in emergencies. Romantic expectations of out of hours care cost GPs dear. PMID- 8520293 TI - Treatment of acute anaphylaxis. Remove the patient from contact with the allergen. PMID- 8520292 TI - Treatment of acute anaphylaxis. Benign allergic reactions should not be treated with adrenaline. PMID- 8520294 TI - Treatment of acute anaphylaxis. Surviving the journey is a good prognostic indicator. PMID- 8520295 TI - Treatment of acute anaphylaxis. Avoid subcutaneous or intramuscular adrenaline. PMID- 8520296 TI - Treatment of acute anaphylaxis. Expressing the dose of adrenaline in milligrams is easier. PMID- 8520297 TI - Treatment of acute anaphylaxis. Investigations help to confirm diagnosis. PMID- 8520298 TI - Treatment of acute anaphylaxis. Treatment takes precedence over monitoring. PMID- 8520299 TI - Treatment of acute anaphylaxis. Chart helps with calculation of dose of adrenaline for children. PMID- 8520300 TI - Symptomatic carotid lesions in young adults. PMID- 8520301 TI - Treatment of acute anaphylaxis. Teachers need to know the basics too. PMID- 8520302 TI - Beneficial effects of simvastatin may be due to non-lipid actions. PMID- 8520303 TI - Withdrawing artificial feeding from children with brain damage. Tortuous arguments evade the issue. PMID- 8520304 TI - Withdrawing artificial feeding from children with brain damage. Treatment without benefit is irresponsible. PMID- 8520305 TI - Hypocholesterolaemia in hairy cell leukemia. PMID- 8520306 TI - Causal link between low cholesterol and cancer is unlikely. PMID- 8520307 TI - Primary care in accident and emergency departments. Cost of employing general practitioners in department may outweigh savings. PMID- 8520308 TI - Primary care in accident and emergency departments. Outcomes of study cast doubt on sensitivity of triage decisions and triage criteria. PMID- 8520309 TI - Primary care in accident and emergency departments. Parents practise triage for paediatric attendances. PMID- 8520310 TI - Beware of the distorting interpreter. PMID- 8520311 TI - Critique of fundholding study contained errors. PMID- 8520312 TI - The case for student fundholding. PMID- 8520313 TI - Shifting the balance from secondary to primary care. PMID- 8520314 TI - A new agenda for AIDS research. PMID- 8520315 TI - Fetal surgery. PMID- 8520316 TI - Private finance, public risk. PMID- 8520317 TI - Private sector to fund new wave of NHS hospitals. PMID- 8520318 TI - Review confirms lumpectomy as safe as mastectomy. PMID- 8520320 TI - Japan tries to catch up on US genetics. PMID- 8520319 TI - US awards patent for tribesman's DNA. PMID- 8520321 TI - Inquiry calls for tighter supervision of British trainees. PMID- 8520322 TI - Survey shows widespread rationing in NHS. PMID- 8520323 TI - Italian doctors continue strike action. PMID- 8520324 TI - Long-term care pushed on to NHS. PMID- 8520325 TI - Australia aims for smoke free cars and Olympics. PMID- 8520326 TI - AIDS rates rise in younger groups. PMID- 8520327 TI - US doctors reject patients' wishes. PMID- 8520328 TI - Outpatient waiting times scrutinised. PMID- 8520329 TI - Shake up for blood transfusion service. PMID- 8520330 TI - Threats and opportunities in accident and emergency. PMID- 8520331 TI - Diet and overall survival in elderly people. AB - OBJECTIVE: To assess the influence of a specific dietary pattern on overall survival. DESIGN: Cohort study. SETTING: Three rural Greek villages, the data from which were collected as part of an international cross cultural study of food habits in later life. SUBJECTS: 182 elderly residents of the three villages. MAIN OUTCOME MEASURE: Overall mortality. RESULTS: Diet was assessed with a validated extensive semiquantitative questionnaire on food intake. A one unit increase in diet score, devised a priori on the basis of eight component characteristics of the traditional common diet in the Mediterranean region, was associated with a significant 17% reduction in overall mortality (95% confidence interval 1% to 31%). CONCLUSION: A diet meeting currently understood health criteria does predict survival among people. PMID- 8520332 TI - Cost effectiveness of antenatal screening for cystic fibrosis. AB - OBJECTIVE: To estimate the cost effectiveness of different antenatal screening programmes for cystic fibrosis. SETTING: Antenatal clinics and general practices in the United Kingdom. DESIGN: Four components of the screening process were identified: information giving, DNA testing, genetic counselling, and prenatal diagnosis. The component costs were derived from the literature and from a pilot screening study in Yorkshire. The cost of a given screening programme was then obtained by summing the components according to the specific screening strategy adopted (sequential and couple), the proportion of carriers detected by the DNA test, and the uptake of screening. Baseline assumptions were made about the proportion with missing information on carrier status from previous pregnancies (20%), the proportion changing partners between pregnancies (20%), and the uptake of prenatal diagnosis (100%). Sensitivity analysis was performed by varying these assumptions. MAIN OUTCOME MEASURE: Cost per affected pregnancy detected. RESULTS: Under the baseline assumptions sequential screening costs between pounds 40,000 and pounds 90,000 per affected pregnancy detected, depending on the carrier detection rate and uptake. Couple screening was more expensive, ranging from pounds 46,000 to pounds 104,000. From the sensitivity analysis a 10% change in the assumed proportion with missing information from a previous pregnancy alters the cost by pounds 4000; a 10% change in the proportion with new partners has a similar effect but only for couple screening; and cost will change directly in proportion to the uptake of prenatal diagnosis. CONCLUSIONS: While economic analysis cannot determine screening policy, the paper provides the NHS with the information on cost effectiveness needed to inform decisions on the introduction of a screening service for cystic fibrosis. PMID- 8520333 TI - Acute injuries in soccer, ice hockey, volleyball, basketball, judo, and karate: analysis of national registry data. AB - OBJECTIVE: To determine the acute injury profile in each of six sports and compare the injury rates between the sports. DESIGN: Analysis of national sports injury insurance registry data. SETTING: Finland during 1987-91. SUBJECTS: 621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. MAIN OUTCOME MEASURES: Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. RESULTS: 54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20 24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. CONCLUSIONS: Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball. PMID- 8520334 TI - Does the onset of tuberculosis in AIDS predict shorter survival? Results of a cohort study in 17 European countries over 13 years. AIDS in Europe Study Group. AB - OBJECTIVE: To assess the impact of tuberculosis on mortality in patients with AIDS. DESIGN: Community based cohort study. SETTING: 52 centres in 17 countries (AIDS in Europe study). SUBJECTS: 5249 patients who were alive and free of tuberculosis one month after the diagnosis of AIDS, enrolled between 1979 and 1989, and followed up until 1992. MAIN OUTCOME MEASURES: Onset of clinically active tuberculosis or death, or both. RESULTS: During a mean follow up period of 15 months 201 (4%) patients developed tuberculosis and 3889 (74%) died. Patients who developed tuberculosis survived significantly longer (median 22 months) than those who did not (median 16 months). This apparent survival advantage was due to patients who survived longer having more opportunity to develop tuberculosis (or any other disease). In models that took into account the time at which tuberculosis was diagnosed, the onset of tuberculosis was associated with a significant increase in mortality (adjusted relative hazard of death 1.34; 95% confidence interval 1.12 to 1.60). CONCLUSIONS: The onset of tuberculosis in patients with AIDS predicts a substantial increase in mortality. Whether this increased mortality is directly attributable to the tuberculosis remains uncertain. If the association is causal preventive chemotherapy and aggressive treatment of tuberculosis could improve survival in AIDS. PMID- 8520335 TI - Falling incidence of penis cancer in an uncircumcised population (Denmark 1943 90) PMID- 8520336 TI - Bronchospasm associated with cisapride. PMID- 8520337 TI - Respiratory distress and royal jelly. PMID- 8520338 TI - Rhabdomyolysis and multiple system organ failure with streptokinase. PMID- 8520339 TI - Do clinical guidelines introduced with practice based education improve care of asthmatic and diabetic patients? A randomised controlled trial in general practices in east London. AB - OBJECTIVE: To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training, inner city general practices. DESIGN: Randomised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions. SUBJECTS: 24 inner city, non-training general practices. SETTING: East London. MAIN OUTCOME MEASURES: Recording of key variables in patient records (asthma: peak flow rate, review of inhaler technique, review of asthma symptoms, prophylaxis, occupation, and smoking habit; diabetes: blood glucose concentration, glycaemic control, funduscopy, feet examination, weight, and smoking habit); size of practice disease registers; prescribing in asthma; and use of structured consultation "prompts." RESULTS: In practices receiving diabetes guidelines, significant improvements in recording were seen for all seven diabetes variables. Both groups of practices showed improved recording of review of inhaler technique, smoking habit, and review of asthma symptoms. In practices receiving asthma guidelines, further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma. Sizes of disease registers were unchanged. The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma. CONCLUSIONS: Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city, non-training practices. The use of simple prompts may enhance this improvement. PMID- 8520340 TI - Robots in operating theatres. AB - Robots designed for surgery have three main advantages over humans. They have greater three dimensional spatial accuracy, are more reliable, and can achieve much greater precision. Although few surgical robots are yet in clinical trials one or two have advanced to the stage of seeking approval from the UK's Medical Devices Agency and the US Federal Drug Administration. Safety is a key concern. A robotic device can be designed in an intrinsically safe way by restricting its range of movement to an area where it can do no damage. Furthermore, safety can be increased by making it passive, guided at all times by a surgeon. Nevertheless, some of the most promising developments may come from robots that are active (monitored rather than controlled by the surgeon) and not limited to intrinsically safe motion. PMID- 8520341 TI - Is tuberculosis taken seriously in the United Kingdom? AB - Tuberculosis has been the subject of much concern in recent years. Notifications have increased, inadequacies in surveillance revealed, and policies for BCG immunisation and screening of immigrants questioned. Until recently the disease was given low priority in the United Kingdom. There is no overall strategic framework for tackling tuberculosis, and fears have been expressed about the future of local tuberculosis control programmes in the new market economy of the NHS. An action plan for tuberculosis within the context of a national programme is urgently required. Only then will a major impact on the incidence of the disease be seen. PMID- 8520342 TI - Cardiac arrest due to severe hyperkalaemia in patient taking nabumetone and low salt diet. PMID- 8520343 TI - Electronic mail. AB - Electronic mail (email) has many advantages over other forms of communication: it is easy to use, free of charge, fast, and delivers information in a digital format. As a text only medium, email is usually less formal in style than conventional correspondence and may contain acronyms and other features, such as smileys, that are peculiar to the Internet. Email client programs that run on your own microcomputer render email powerful and easy to use. With suitable encoding methods, email can be used to send any kind of computer file, including pictures, sounds, programs, and movies. Numerous biomedical electronic mailing lists and other Internet services are accessible by email. PMID- 8520344 TI - A lump in the chest. A common problem in an unusual setting. PMID- 8520345 TI - ABC of atrial fibrillation. Differential diagnosis of atrial fibrillation. PMID- 8520346 TI - Hepatitis B vaccination policy in drug treatment services. PMID- 8520347 TI - Primary health care and adolescence. PMID- 8520348 TI - Pregnant women should wear seat belts. PMID- 8520349 TI - Tobacco companies violated advertising restriction. PMID- 8520350 TI - Hazards of beta blockade. Pressor effects may be important. PMID- 8520351 TI - Informed consent for trial of elective ventilation will not be forthcoming. PMID- 8520352 TI - Misuse of dothiepin. PMID- 8520353 TI - Withdrawing artificial feeding from children with brain damage. PMID- 8520354 TI - Palliative care in general practice. Should GPs do it at the expense of commoner problems? PMID- 8520355 TI - Palliative care in general practice. Palliative care is integral to practice. PMID- 8520356 TI - Reflex sympathetic dystrophy in children. Dystrophic changes are less likely. PMID- 8520357 TI - Significant social class gradient in menstrual disorders. PMID- 8520358 TI - Relax sympathetic dystrophy in children. Active early physiotherapy is the key to prevention. PMID- 8520359 TI - Audit suggests that use of aspirin is rising in coronary heart disease. PMID- 8520360 TI - Child health booklets lack illustration of meningococcal rash. PMID- 8520361 TI - Water shortage in West Yorkshire has serious health implications. PMID- 8520362 TI - Breast cancer and hormonal supplements in postmenopausal women. Benefits probably outweight risks. PMID- 8520363 TI - Breast cancer and hormonal supplements in postmenopausal women. Article increased uncertainty. PMID- 8520364 TI - Breast cancer and hormonal supplements in postmenopausal women. Increase in risk of breast cancer is small. PMID- 8520365 TI - Thrombolytic treatment. Pulse spray infusion works faster but is more expensive. PMID- 8520366 TI - Are second opinions a right or a concession? An important political issue. PMID- 8520367 TI - Are second opinions a right or a concession? Case history breached confidentiality. PMID- 8520368 TI - Thrombolytic treatment. Streptokinase is more economical than alteplase. PMID- 8520369 TI - Thrombolytic treatment. Timing is more important than choice of agent. PMID- 8520370 TI - Are second opinions a right or a concession? New developments have transformed outlook for patients with schizophrenia. PMID- 8520371 TI - Managing in flight emergencies. Emergency kit will now contain fatal dose of lignocaine. PMID- 8520372 TI - Managing in flight emergencies. Glove and cannula approach is easier. PMID- 8520373 TI - Taxi rank malaria. PMID- 8520374 TI - Managing in flight emergencies. Plane should not have left the ground. PMID- 8520375 TI - American cardiothoracic trainees want longer hours too. PMID- 8520376 TI - Continuing confusion over the eponymous possessive. PMID- 8520377 TI - Surgery and radiotherapy for early breast cancer. PMID- 8520378 TI - Brachial plexus neuropathy after radiotherapy for breast cancer. PMID- 8520379 TI - Clinical guidelines and the law. PMID- 8520380 TI - Misoprostol in patients taking non-steroidal anti-inflammatory drugs. PMID- 8520381 TI - Doctors and medical politics. PMID- 8520382 TI - The costs of prevention. PMID- 8520383 TI - French doctors protest over health and welfare reforms. PMID- 8520384 TI - Japan criticised for unsafe drug licences. PMID- 8520386 TI - Scotland's "right to die" case is put on hold. PMID- 8520385 TI - Iraq sanctions lead to half a million child deaths. PMID- 8520387 TI - Harvard dispenses medical information to the world. PMID- 8520388 TI - Health ministers look at cross border prescriptions. PMID- 8520390 TI - Heart disease prevention needs attention. PMID- 8520389 TI - American doctors alerted to assault. PMID- 8520392 TI - Ombudsmen in the operating theatre. PMID- 8520391 TI - Belgium brews row over euthanasia. PMID- 8520393 TI - Adverse life events and breast cancer: case-control study. AB - OBJECTIVE: To investigate the strength of association between past life events and the development of breast cancer. DESIGN: Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. SETTING: Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King's College Hospital, London. SUBJECTS: 119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. MAIN OUTCOME MEASURES: Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. RESULTS: 41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. CONCLUSION: These findings suggest an aetiological association between life stress and breast cancer. PMID- 8520394 TI - Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts. AB - OBJECTIVE: To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN: Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING: Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS: Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES: Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS: Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION: About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality. PMID- 8520395 TI - Trends in incidence of AIDS associated with transfusion of blood and blood products in Europe and the United States, 1985-93. AB - OBJECTIVE: To quantify patterns and trends in incidence of AIDS associated with transfusion of blood and its products in 14 European countries and the United States. DESIGN: Data were derived from the World Health Organisation's European non-aggregate AIDS dataset and, for the United States, from the Centers for Disease Control AIDS public information dataset. Rates were standardised by using the world standard populations and adjusted for reporting delays in each country. SUBJECTS: Cases of AIDS in patients with haemophilia and recipients of transfusions. RESULTS: Overall, between 1985 and 1993 almost 6000 cases of AIDS associated with transfusions were registered in the 14 European countries considered and over 8000 in the United States between 1985 and 1992. Most European countries had annual age adjusted rates lower than 0.5 per million children aged 12 or less and between 1 and 2 per million adults. The United States had rates around 1 per million children and 5 per million adults in the most recent period. For children, the highest rates were generally reached in 1985-7, whereas in adults the highest rates were in the late 1980s. France had the highest overall incidence of AIDS related to transfusion in Europe (3.3 per million). Romania had a major epidemic in children (over 30 cases per million children in 1988-90). Incidence rates of AIDS associated with transfusion were still increasing in some southern European countries in the early 1990s. CONCLUSIONS: Apart from in France and Romania it is clear that rates of bloodborne AIDS in European countries are lower than those registered in the United States. PMID- 8520396 TI - Prognostic trees to aid prognosis in patients with cutaneous malignant melanoma. Scottish Melanoma Group. AB - OBJECTIVES: To design user friendly guides to prognosis for patients who have had invasive primary cutaneous malignant melanomas surgically excised. DESIGN: Adaptation of the classification tree method was used to derive prognostic trees for four different subgroups of malignant melanoma patients in whom known and possible prognostic variables interacted in different ways. SETTING: Scotland. SUBJECTS: Statistical modelling for prognostic trees was based on 1978 patients whose primary malignant melanoma was first diagnosed in 1979-86 for whom five year follow up and all relevant clinical pathological data were available. The resultant model was validated with 300 patients first diagnosed in 1987 for whom the same information was available. MAIN OUTCOME MEASURES: Actual and predicted rate of survival after diagnosis of primary cutaneous malignant melanoma. RESULTS: The four subgroups of patients were men and women with ulcerated and non ulcerated cutaneous primary melanomas. Validation of the model showed excellent agreement between actual status of patients in the relevant subgroups and their status as predicted by the model. CONCLUSIONS: The prognostic trees are simple to use and give more accurate prognosis for individual patients than is currently available from tumour thickness alone. PMID- 8520397 TI - Prescribing of quinine and cramp inducing drugs in general practice. PMID- 8520398 TI - High frequency of parvovirus B19 in patients tested for rheumatoid factor. PMID- 8520399 TI - The effects of fundholding in general practice on prescribing habits three years after introduction of the scheme. AB - OBJECTIVES: To observe changes in prescribing practice that occurred after the introduction of fundholding in first wave practices and to contrast these with changes occurring in similar non-fundholding practices. DESIGN: Prospective observational study. SETTING: Oxford region fundholding study. SUBJECTS: Eight first wave fundholding practices and five practices that were not interested in fundholding in 1990-1, which were similar in terms of practice size, training status, locality, and urban rural mix. Three of the fundholding and none of the non-fundholding practices were dispensing practices. MAIN OUTCOME MEASURES: Changes in prescribing practice as measured by net cost per prescribing unit, cost per item, number of items prescribed, and substitution rates for generic drugs three years after the introduction of fundholding. Data for fundholding practices were analysed separately according to whether they were dispensing or non-dispensing practices. RESULTS: Prescribing costs rose by a third or more in all types of practice. The patterns of change observed in this cohort after one year of fundholding were reversed. No evidence existed that fundholding had controlled prescribing costs among non-dispensing fundholders; costs among dispensing fundholders rose least, but the differences were small compared with the overall increase in costs. CONCLUSIONS: Early reports of the effectiveness of fundholding in curbing prescribing costs have not been confirmed in this longer term study. PMID- 8520400 TI - Characteristics of general practices that prescribe appropriately for asthma. PMID- 8520401 TI - Parvovirus B19: an expanding spectrum of disease. PMID- 8520402 TI - Guide to the Internet. The world wide web. AB - The world wide web provides a uniform, user friendly interface to the Internet. Web pages can contain text and pictures and are interconnected by hypertext links. The addresses of web pages are recorded as uniform resource locators (URLs), transmitted by hypertext transfer protocol (HTTP), and written in hypertext markup language (HTML). Programs that allow you to use the web are available for most operating systems. Powerful on line search engines make it relatively easy to find information on the web. Browsing through the web--"net surfing"--is both easy and enjoyable. Contributing to the web is not difficult, and the web opens up new possibilities for electronic publishing and electronic journals. PMID- 8520403 TI - Effect of recent health and social service policy reforms on Britain's mental health system. AB - The introduction of new policies in health and social services in Britain has changed the way community care is provided to seriously mentally ill people. Britain is creating the same problems that have existed in the United States, whereby clinicians struggle to provide services in an environment with multiple payers and perverse incentives. A simple system in Britain has been replaced with complicated organisational and financial structures that require almost impossible feats by local health and social service staff to coordinate care for patients for whom continuity of care is critical for their survival in the community and their wellbeing. Seriously mentally ill people are in the middle of these complicated problems. The creation of a local mental health authority that could be held responsible for community care, as exists in some American states, may be one solution. PMID- 8520404 TI - OxDONS syndrome: the inevitable disease of the NHS reforms. AB - The financial demise of Oxford's department of neurosurgery (OxDONS) was precipitated by the financial rules of the reformed NHS. In particular it was produced by the failure of "resources to follow patients"; the requirement that "prices have to follow costs"; and the use of private income for revenue expenditure, not capital expenditure. This process will eventually affect all hospital departments, but it affected the unit in Oxford sooner as it started as "efficient"--that is, underresourced--and has depended on income from extracontractual referrals and private work. Current NHS accounting rules act as a disincentive to private income being generated in NHS hospitals, and consultants should be aware of this. PMID- 8520405 TI - ABC of atrial fibrillation. Investigation and non-drug management of atrial fibrillation. PMID- 8520406 TI - Controversy over psychiatric tourism. A real phenomenon ... PMID- 8520407 TI - Controversy over psychiatric tourism ... but short on evidence. PMID- 8520408 TI - Controversy over psychiatric tourism. Absence of data fuels "foreign scroungers" mentality. PMID- 8520409 TI - Tackling general practitioners' depression. Educational strategies to prevent depression. PMID- 8520410 TI - Obesity in Britain. Lifestyle data do not support sloth hypothesis. PMID- 8520411 TI - Monitoring the safety of herbal remedies. Herbal remedies have a heterogeneous nature. PMID- 8520412 TI - Obesity in Britain. Rising trend may be due to "pathoenvironment". PMID- 8520413 TI - Monitoring the safety of herbal remedies. WHO project is under way. PMID- 8520414 TI - Depression, antidepressants, and accidents. PMID- 8520415 TI - Monitoring the safety of herbal remedies. European pilot studies are under way. PMID- 8520416 TI - Patients often present too late for inclusion in trials. PMID- 8520417 TI - Local research ethics committees. Local committees have strengths too. PMID- 8520418 TI - Local research ethics committees. Attitude of their members is the critical factor. PMID- 8520419 TI - Local research ethics committees. Central ethics committee might have to face hostile locals. PMID- 8520420 TI - Local research ethics committees. Problems of students must not be ignored. PMID- 8520421 TI - Local research ethics committees. Committees should devise special forms for the social sciences. PMID- 8520422 TI - Local research ethics committees. Differences in application process cause problems. PMID- 8520423 TI - Medical insurance in Republic of Ireland. PMID- 8520424 TI - Improving oral examinations. Interobserver agreement does not necessarily imply reliability. PMID- 8520425 TI - Attitudes of consultant physicians to Calman proposals. Royal College of Physicians gave qualified support to proposals. PMID- 8520426 TI - Summative assessment for general practitioner registrars. Has been implemented experimentally in Yorkshire. PMID- 8520427 TI - Summative assessment for general practitioner registrars. Proposals may damage one of finest examples of postgraduate medical education. PMID- 8520428 TI - Attitude of consultant physicians to Calman proposals. Present situation is detrimental to patient care. PMID- 8520429 TI - Attitudes of consultant physicians to Calman proposals. Proposals do not refer to need for consultant provided service. PMID- 8520430 TI - Rising emergency admissions. PMID- 8520431 TI - Patints prefer hospital follow up for cancer. PMID- 8520432 TI - Nurse triage may reduce workload in accident department. PMID- 8520433 TI - Strengths of carotid endarterectomy were understated. PMID- 8520434 TI - [The intensity of protein synthesis in the cells of a diluted hepatocyte culture is higher than in a dense culture]. AB - Incorporation of 3H-leucine in proteins and radioactivity of free leucine have been studied in hepatocyte culture on collagen-coated glass. A high density culture obtained from a suspension of isolated rat hepatocytes at 5 x 10(6) cells/ml was compared with low density cultures diluted from the same suspension 10- to 20-fold. The incorporation pool ratio showing the efficiency of the precursor utilization was higher in the low density culture as compared with the high density monolayer. The effect was due to disproportionate low pool in the diluted cultures. The total radioactivity of proteins was lower in the diluted cultures as compared with the monolayer, although the incorporation was not in proportion with the cell density. Specific rate of protein synthesis (per cell) was higher in the diluted cultures than in the monolayer. PMID- 8520435 TI - [Proteinases activated by gamma irradiation in the nuclei of rat peripheral blood leukocytes]. AB - The nuclei of the peripheral blood leucocytes of rats displayed proteolytic activity (Ca-dependent with pH optimum 8.5 and active at alkaline pH), whose level increases under the influence of gamma-irradiation. These proteases were partially purified and identified. It was shown using gel chromatography, affinity chromatography with casein-sepharose and enzyme-electrophoresis that these proteolytic activities are related to one protein with a molecular mass of 24 kDa or a complex of proteins that do not cleave under the given experimental conditions. The both protease activities are predominantly blocked by inhibitors of cysteine proteases. PMID- 8520436 TI - [The anti-infective properties of mammalian earwax]. AB - The cerumen (earwax) of some mammals possesses antistaphylococcal, antimicrococcal and antiherpes activities. The cerumen of two thirds of individuals, irrespective of their species identity and sex, has antiviral properties. The mean chemotherapeutical index in the studied groups follows a significantly decreasing sequence: dogs, humans without signs of herpes infections, rabbits, and humans with clinically expressed herpes infection. Cerumen of almost 25% of humans of the compared groups displays the immunostimulating activity. The cerumen of all studied individuals contains yeast like fungi. A suggestion is put forward that the products of their metabolism stimulate local release of interferon-like substances by the lymphoid tissue in the cerumen. PMID- 8520437 TI - [Amyloidosis of the iris and sclera in the pathogenesis of glaucoma]. AB - Morphological analysis of 173 biopsies of the iris and sclera removed during antiglaucoma operations in 115 patients with open angle glaucoma showed extracellular deposits of amyloid in 44.4% of cases, which complicated the course of glaucomatous process and had pathogenetic importance. Amyloid was identified by Congo red [correction of Congo-rot] staining with the control in the polarized light and also by toluidine blue staining for chondroitin and dermatan sulfates. The vascular and muscle (pupillary muscle) forms of amyloidosis were found in the iris and the pericollagen and focal forms in the drainage system and sclera. We propose to classify the amyloid form of glaucoma with specific morphological picture. PMID- 8520438 TI - [The sex dimorphism of the hepatoid circumanal glands in the dog and the dynamics of its development]. AB - The histology of sexual dimorphism of the dog hepatoid circumanal glands has not been studied before. Studies of hepatoid and other skin glands of the circumanal region of adult dogs and puppies (1 and 38 days) of both sexes have shown striking differences in the structure of this region in adult males and females and complete qualitative similarity in puppies of the both sexes. The hepatoid glands of adult males form a massive glandular layer comprising 91% of the skin thickness and supplanting all other glandular types. In adult females these glands are reduced to widely spaced islets (12% of the skin thickness), and the apocrine glands are the prevailing glandular type (53%). The hepatoid glands of puppies of the both sexes develop according to the same structural scheme, approaching rapidly to the glands of adult males. In female puppies they develop more rapidly, and at the age of 38 days their absolute size (length of glandular lobes) is already thrice that of adult females. The hepatoid glands of adult females undergo a very significant regress and possess several structural features suggesting their degeneration. PMID- 8520439 TI - [The characteristics of the population of the deep waters of the Norwegian Sea in the region of the loss of the Komsomolets nuclear-powered submarine]. AB - Specific features of vertical distribution and migration of planktonic organisms were studied for estimation of direct pathway of distribution of radionuclides in case they are released in the environment from the sunk nuclear submarine "Komsomolets" (73 degrees 42'N, 13 degrees 15'E, depth 1700 m). The materials were collected by 150-liter bathometers and planktonic nets in July 1994. In addition, planktonic animals were directly counted from deep-sea submarines "Mir". Distribution of the total biomass of plankton was considered and distribution in the water column from the surface to the depth 1700 m was quantitatively estimated for the following species: Calanus finmarchicus, C. hyperboreus, Metridia longa, Euchaeta spp., Sagitta elegans, Themisto abyssorum, and Hymenodora glacialis. The Norway sea hollow is filled by the local Arctic water and this facilitates penetration of many species during seasonal and other migrations down to the demersal layers, i.e., to depths, which are not specific for these organisms in basins with usual water stratification. Mass accumulations of Th. abyssorum have been found in the demersal layer, which is a main component of feeding of commercial plankton-eating fish as well as migrations of this crustacean across the water. PMID- 8520440 TI - Renal dysfunction and endotoxaemia in obstructive jaundice. PMID- 8520441 TI - Peripheral blood stem cell transplants. PMID- 8520442 TI - Albendazole in neurocysticercosis. AB - BACKGROUND: In India, parenchymatous cysticercus cysts are more common than the meningeal racemose variety which are seen frequently in Latin America. Reports from Mexico suggest that albendazole is effective in the treatment of neurocysticercosis. We, therefore, studied whether this drug changed the natural course of neurocysticercosis in India. METHODS: In a randomized, double-blind, placebo controlled study, we allocated 29 consecutive patients (22 men and 7 women) with multiple cystic lesions on computed tomography (CT) of the head suggestive of cysticercosis to 7 days treatment with albendazole (15 mg/kg/day) or placebo. CT scans were repeated at the end of treatment and 1 and 3 months later to assess the number of cysts and extent of oedema. RESULTS: Sixteen patients received albendazole and 13 placebo. No change was seen at the end of one week. At 3 months, 14 patients in the albendazole group and 10 in the placebo group showed more than 25% reduction in the number of lesions. The difference between the two groups was not significant. CONCLUSION: Albendazole given in a dose of 15 mg/kg/day for 1 week does not change the natural course of neurocysticercosis. PMID- 8520443 TI - Comparison of disease-specific and a generic quality of life measure in patients with bronchial asthma. AB - BACKGROUND: Quality of life is being increasingly recognized as an important outcome in chronic and terminal illnesses. There are few publications from India on the characteristics of the instrument that measures quality of life in clinical trials. We describe a method for choosing an appropriate instrument in a randomized trial. METHODS: We selected thirty-two patients with bronchial asthma randomly and evaluated them to compare the validity and responsiveness of the disease-specific quality of life instrument in asthma (AQL) and the generic quality of life instrument, 'Sickness impact profile' (SIP), to detect changes in their health status. Validity was determined by a priori constructs (construct validation) and the responsive coefficient was calculated by determining the relationship to the 'minimal significant change in asthma score' and the 'variability' seen in this change in stable patients. RESULTS: The constructs used in validating the scores were that the change in quality of life score would correlate (i) highly with change in self-assessment of the disease (r > 0.7), (ii) moderately with change in physician assessment of the disease (r > 0.5), and (iii) minimally with change in peak flow reading (r > 0.3). We found both instruments to have good construct validity. The responsiveness coefficients noted for AQL and SIP were 1.8 (CI 0.65-3) and 0.7 (CI 0.3-1.2), respectively. CONCLUSIONS: Though both AQL and SIP were valid measures of quality of life, AQL is likely to be more capable of detecting smaller changes in the health status of patients with bronchial asthma and hence was chosen as the instrument in the proposed clinical trial. PMID- 8520444 TI - Value of antibiotic therapy in tuberculin-positive children with parenchymal lung lesions. AB - BACKGROUND: A tuberculin-positive child with radiological evidence of a parenchymal lung lesion is likely to be treated for tuberculosis by a physician. However, non-tuberculous microbial infections may also cause parenchymal lung lesions. We tried to distinguish tuberculous from non-tuberculous lung lesions by administering a course of antibiotics. METHODS: Three hundred and five tuberculin positive children with parenchymal lung lesions due to pneumonia, bronchiectasis (cylindrical and reversible) and minor fissure opacification were studied at the Tuberculosis Clinic, Institute of Child Health, Madras. Those with more serious forms of tuberculosis like miliary, cavitary and segmental lesions and with grade III and IV undernutrition were excluded. Three weeks of oral antibiotic therapy, with erythromycin (30 mg/kg/day) and chloramphenicol (50 mg/kg/day) for the first two weeks followed by co-trimoxazole (trimethoprim 6 mg/kg/day and sulphamethoxazole 25 mg/kg/day) for the third week, was given. Chest X-rays were taken before and after antibiotic therapy. RESULTS: Sixty per cent of the children with pneumonia, 57% with bronchiectasis and 62% with minor fissure opacification showed complete radiological clearance. CONCLUSION: In tuberculin positive children with parenchymal lung lesions radiological clearance was seen in 60% after three weeks of antibiotic therapy indicating that the parenchymal lung lesions were caused by non-tuberculous organisms. Hence a course of antibiotic therapy in these children may have diagnostic value as well as considerable financial, social and therapeutic implications. PMID- 8520445 TI - Gene therapy. AB - Gene therapy replaces or supplements the activity of a resident defective or missing gene by a cloned functional one. A functional gene may be delivered to the target tissues ex vivo or in vivo using various physical methods and several chemical and biological vehicles. In this article we present an overview of different experimental models and the progress made in clinical studies on gene therapy and discuss the prospects of the antisense approach and the ethical concerns related to the technique. PMID- 8520447 TI - Endoscopic stenting v. surgical bypass in low bile duct obstruction. PMID- 8520446 TI - Is medical treatment of neurocysticercosis effective? PMID- 8520448 TI - Modulation of coronary endothelial function by lovastatin. PMID- 8520449 TI - Medical emergencies in oncology. PMID- 8520450 TI - Structural adjustment and India's health. PMID- 8520452 TI - Physician-assisted suicide. PMID- 8520451 TI - Sir William Osler's life and humanity. PMID- 8520453 TI - How can Africans be persuaded to stop smoking? PMID- 8520455 TI - Air-conditioning in hospitals. PMID- 8520454 TI - Pulmonary tuberculosis after fludarabine for chronic lymphocytic leukaemia. PMID- 8520456 TI - AIIMS: Its problems and their treatment. PMID- 8520457 TI - Nursing homes. PMID- 8520458 TI - AIDS--reply to J. Nandi. PMID- 8520459 TI - The plague. PMID- 8520460 TI - Synaptic like microvesicles: do they participate in regulated exocytosis? AB - Synaptic like microvesicles (SLMV) form a pleiomorphic population of vesicles present in neuroendocrine cells of the pituitary and the adrenal medulla. Their composition and biogenesis is very similar to small synaptic vesicles (SSV) present in nerve terminals. Membrane proteins of SSV involved in fusion (synaptotagmin) and trafficking (Rab 3) together with synaptophysin have been identified on SLMV. The SLMV from pancreatic beta cells store GABA, those present in chromaffin cells catecholamines and/or acetylcholine. We conclude that SLMV may participate in regulated exocytosis based on (a) their localization near release sites, (b) their content and (c) their membrane composition. The functional meaning and the way this process is regulated remain to be elucidated. PMID- 8520461 TI - Guanidino compound levels in brain regions of non-dialyzed uremic patients. AB - Guanidino compounds have been suggested to contribute to the complex neurological complications associated with uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of alpha-keto-delta-guanidinovaleric acid, alpha-N-acetylarginine and beta-guanidinopropionic acid remained below detection limits. Creatine, guanidinoacetic acid, argininic acid, gamma-guanidinobutyric acid, arginine and homoarginine were not increased in uremic patients. Argininic acid and homoarginine were detectable in some brain regions only. Creatine concentrations varied from 2500 +/- 2100 nmol/g tissue in hypophysis to 10500 +/- 1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for gamma-guanidinobutyric acid with the lowest concentration in the caudate nucleus (0.6 +/- 0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3 +/- 2.8 nmol/g tissue). The guanidinosuccinic acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of guanidinosuccinic acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of guanidinosuccinic acid increased with increasing degree of renal failure with levels up to 65 nmol/g tissue in the hypophysis. Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum urea levels. Guanidine and methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of guanidinosuccinic acid and creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable uremic toxins contributing to the neurological complications in uremia. PMID- 8520462 TI - The source of brain adenosine outflow during ischemia and electrical stimulation. AB - Adenosine outflow and adenosine and adenine nucleotide content of hippocampal slices were evaluated under two different experimental conditions: ischemia-like conditions and electrical stimulation (10 Hz). Five minutes of ischemia-like conditions brought about an 8-fold increase in adenosine outflow in the following 5 min during reperfusion, and a 2-fold increase in adenosine content, a 43% decrease in ATP, a 72% increase in AMP and a 30% decrease in energy charge (EC) at the end of the ischemic period. After 10 min of reperfusion ATP, AMP and EC returned to control values, while the adenosine content was further increased. Five minutes of electrical stimulation brought about an 8-fold increase in adenosine outflow that peaked 5 min after the end of stimulation, a 4-fold increase in adenosine content and an 18% decrease in tissue EC at the end of stimulation. After 10 min of rest conditions the adenosine content and EC returned to basal values. The origin of extracellular adenosine from S adenosylhomocysteine (SAH) was examined under the two different experimental conditions. The SAH hydrolase inhibitor, adenosine-2,3-dialdehyde (10 microM), does not significantly modify the adenosine outflow evoked by electrical stimulation or ischemia-like conditions. This finding excludes a significant contribution by the transmethylation pathway to adenosine extracellular accumulation evoked by an electrical or ischemic stimulus, and confirms that the most likely source of adenosine is from AMP dephosphorylation. PMID- 8520463 TI - Melatonin synthesis in the retina and pineal gland of Djungarian hamsters at different times of the year. AB - Daily profiles of melatonin content in the retina of Djungarian hamsters were measured throughout the course of a year. Peak levels of retinal melatonin were found at various times of the day at different seasons. In a subsequent study we determined concurrently daily profiles of nine indole metabolites (tryptophan, 5 hydroxytryptophan, 5-hydroxytryptamin, 5-hydroxyindoleacetic acid, 5 hydroxytryptophol, N-acetylserotonin, melatonin, 5-methoxyindoleacetic acid and 5 methoxytryptophol) in samples of hamster retina and pineal gland at the four different seasons. Measurements were made using HPLC coupled to a coulometric electrode detection system. Large seasonal variations in the levels and daily rhythm amplitudes of the different indole metabolites were found in the pineal glands. Due to technical problems and unknown interfering substances only tryptophan and serotonin could be determined in the retinas at all four seasons. Despite this, the ability to measure levels of several metabolites in the same sample and in different tissues of the same animals permitted more accurate comparisons of the components involved in melatonin synthesis. Our data suggest that the level of retinal melatonin is regulated and controlled locally within the retina itself. However, long-term feedback mechanisms from other sources of melatonin are not excluded but are rather likely. PMID- 8520464 TI - Agonist-induced effects on cyclic AMP metabolism are affected in pigment epithelial cells of the Royal College of Surgeons rat. AB - Recent work has demonstrated that stimulation of cAMP production via A2-adenosine receptors is reduced in cultured retinal pigment epithelial cells from the RCS rat. Cultured rat RPE cells are also shown to possess beta 2-adrenergic receptors positively coupled to cAMP production. Isoproterenol and salbutamol both stimulate cAMP levels with half maximal (EC50) values of 0.5 and 0.2 microM, respectively. Isoproterenol action is attenuated most effectively by the beta 2 antagonist, ICI 118551, while the beta 1-antagonist, CGP 20712A, is only partially effective. Isoproterenol-stimulated cAMP production is markedly reduced in the RCS rat RPE when compared to control cultures. In passaged RCS rat RPE cells cAMP stimulation by 10 microM isoproterenol was 6.4% of that by control cultures and in primary cultures it was around 75% of controls. The observed EC50 values were 0.4 and 1.3 microM for passaged control and RCS rat RPE cells, respectively. Melatonin negatively influences cAMP production in the RPE via Gi proteins. Melatonin attenuated the action of forskolin by 51.1% in control rat RPE but only by 18.6% in the RCS rat RPE. The dose-response curve for melatonin shows an approximate 1000-fold shift in potency in the RCS rat. bFGF also has an inhibitory effect on rat RPE cells. bFGF (50ng/ml) attenuated forskolin stimulated cAMP levels by 61.9% in control rat RPE but had not effect on the action of forskolin in RCS rat RPE. Serotonin (100 microM) potentiates the forskolin-induced stimulation of cAMP by 140.1%. However, unlike isoproterenol, melatonin and bFGF, the action of serotonin on adenylate cyclase appears normal in the RCS rat RPE. We conclude that the defect in the RCS rat RPE is likely to be due to impaired coupling of the components of the adenylate cyclase system and that this is most probably an abnormal interaction of adenylate cyclase with G protein alpha-subunits. PMID- 8520465 TI - Gating of retinal inputs through the suprachiasmatic nucleus: role of excitatory neurotransmission. AB - The mammalian circadian clock, located in the hypothalamic suprachiasmatic nucleus (SCN) is important in the regulation of many circadian rhythms, including regulation of pineal gland metabolism and melatonin secretion. Transsection of the optic nerves, disrupting the retinohypothalamic pathway, lesion of the SCN, or lesion of the hypothalamic paraventricular nucleus (PVN) abolish the regulation of pineal serotonin N-acetyltransferase activity by light. Therefore, the pathways linking the retina and the pineal gland must be channelled from the retina through the SCN and the PVN. Many lines of evidence indicate that the major neurotransmitter in the retinal afferents is glutamate. The first aim was therefore to study the retinal target neurons by localising glutamate receptors in the rodent SCN. Using in situ hybridisation, we detected NMDA-R1 and NMDA-R2C mRNA subunits in the SCN. Using immunocytochemistry, immunoreactivity for the AMPA type receptors GluR1, GluR2,3 and GluR4 was also detected in the SCN. Presentation of a short light pulse during the subjective night [i.e. circadian time (CT) 14 or 19], when light induced phase-shifting of activity-rest cycles can be accomplished, also induces expression of the immediate early-genes c-fos and junB in the rodent SCN. The second aim was to use this cellular correlate of behavioural function to determine the location of potential retinal target neurons in the SCN, and to investigate the hypothesis that glutamatergic neurotransmission mediates the effects of light on the circadian system. Thus, the ability of the NMDA receptor antagonist MK-801 to block light-induced c-fos expression in the SCN was studied. In the rat, this antagonist blocked c-fos mRNA expression in a subpopulation of cells in the ventral SCN at doses of 6, but not 2 mg/kg. In contrast, in the hamster both doses blocked light-induced c-fos expression in the ventral SCN. These data provide support for the hypothesis that glutamate mediates effects of light in the SCN, although it appers that the complexes of NMDA receptor subunits, which are involved in light-induced expression of c-fos after light, are relatively insensitive to MK-801. The diversity, heterogeneous distribution, and complexity of glutamate receptor subunits in the SCN suggest that processing of light pulses in the SCN is mediated by several cell types in the SCN. Via an integration process in the clock, the transmission of photic information takes place to other brain structures. PMID- 8520466 TI - Mechanism of melatonin signal transduction in the neonatal rat pituitary. AB - Melatonin inhibits GnRH-induced LH release from anterior pituitary of the neonatal rat. It acts via specific high affinity receptors and decreases concentrations of intracellular calcium ([Ca2+]i) and cyclic AMP. To determine which of these second messengers transduces the melatonin inhibition of LH release, we have tested the effect of melatonin in the presence of specific drugs affecting either of these second messengers. Calcium channel antagonist nifedipine inhibited LH release from cultured pituitary to a similar degree as did melatonin and prevented the inhibitory effect of melatonin on LH release. Calcium channel agonist. Bay K potentiated the LH release and reduced the inhibitory effect of melatonin. This observation constitutes strong evidence that melatonin inhibits LH release via inhibition of calcium influx through voltage sensitive channels. The cyclic AMP derivative 8-bromo-cAMP potentiated GnRH stimulation of LH release but did not prevent the melatonin-induced inhibition of the release. However, when used in combination with low concentration of Bay K, which alone reduced the melatonin effect only partially, 8-bromo-cAMP completely blocked the melatonin effect. This observation suggests that both cAMP and [Ca2+]i may be involved in the effect of melatonin on LH release. PMID- 8520467 TI - Are there dopaminergic ganglion cells in the mammalian retina? AB - New improvements of the tyrosine hydroxylase immunocytochemical labelling in wholemounts allowed us to visualize tyrosine hydroxylase-immunoreactive fibres in the nerve fibre layer of the mouse, rat and macaque monkey retinas. These fibres could not be related to labelled somata in the retina. Their possible origin from ganglion cells or brain nuclei is discussed. PMID- 8520468 TI - Arylamine and arylalkylamine N-acetyltransferases in retina, pineal gland, brain and liver of chicks: a comparative study. AB - Regulation of arylamine N-acetyltransferase (A-NAT) and arylalkylamine N acetyltransferase (AA-NAT) was examined in retina, pineal gland, brain and liver of chicks. Enzyme activities were determined using as substrates p-phenetidine and procainamide for A-NAT, tryptamine and phenethylamine for AA-NAT. The activity of A-NAT in all tissues studied does not appear to be regulated by a light-dark cycle. On the other hand, AA-NAT showed distinct light-dark dependent changes (with high values at night) in the retina and pineal gland, but not in brain and liver. The nocturnal increase of retinal and pineal AA-NAT activity was prevented by cycloheximide; the drug did not affect A-NAT activity in these tissues. Treatment of light-adapted chicks with aminophylline significantly increased AA-NAT activity of the retina and pineal gland, without altering the enzyme activity in brain and liver. In these animals, the activity of A-NAT (procainamide) did not change in any tissue studied, whereas the enzyme activity measured using p-phenetidine as a substrate did decrease but only in the retina. A similar pattern of changes in retinal A-NAT and AA-NAT activities was observed after intraocular injection of d,b-cAMP. The rate of inactivation at 4 degrees C was significantly slower for AA-NAT than A-NAT. NATs from brain and liver displayed the highest and lowest, respectively, liability in the cold. The results indicate that the chick retina contains both A-NAT and AA-NAT. The two enzymes have distinct characteristics and the regulation of their activities is different. The retinal A-NAT is similar to A-NAT present in other tested tissues; however, AA-NAT can be induced at night only in the retina and pineal gland. It is suggested that there are two forms of retinal A-NAT, and that, under specified conditions, the activity of one form (A-NAT; p-phenetidine) may be regulated in an opposite manner to AA-NAT activity. PMID- 8520469 TI - The picornaviral 3C proteinases: cysteine nucleophiles in serine proteinase folds. AB - The 3C proteinases are a novel group of cysteine proteinases with a serine proteinase-like fold that are responsible for the bulk of polyprotein processing in the Picornaviridae. Because members of this viral family are to blame for several ongoing global pandemic problems (rhinovirus, hepatitis A virus) as well as sporadic outbreaks of more serious pathologies (poliovirus), there has been continuing interest over the last two decades in the development of antiviral therapies. The recent determination of the structure of two of the 3C proteinases by X-ray crystallography opens the door for the application of the latest advances in computer-assisted identification and design of anti-proteinase therapeutic/chemoprophylactic agents. PMID- 8520470 TI - Structural analysis of the N- and C-termini in a peptide with consensus sequence. AB - We present a structural analysis of a peptide, the sequence of which includes amino acids that show preferences for specific positions near the N- and C termini in protein helices. This peptide has the sequence ac-YMSEDELKAAEAAFKRHGVP amide, which includes a strong version of an N-terminal Harper-Rose capping box structure as well as a Gly located close to the C-terminus designed to elucidate its role in C-terminal capping. The sequence of five residues at the middle is inserted to separate effects at the two ends via a helix-stabilizing linker. Application of a simulated annealing procedure using interproton distance constraints derived from 1H NOESY experiments in water reveals the presence of a C-terminal structure in this model. The C-terminus forms a folded back structure in a significant fraction of structures generated by the annealing, in most of which Gly assumes an alpha L conformation. This structure occurs within a highly flexible region of the molecule and hence is occupied only a fraction of the time. PMID- 8520471 TI - Characterization of a new four-chain coiled-coil: influence of chain length on stability. AB - Limited information is available on inherent stabilities of four-chain-coils. We have developed a model system to study this folding motif using synthetic peptides derived from sequences contained in the tetramerization domain of Lac repressor. These peptides are tetrameric as judged by both gel filtration and sedimentation equilibrium and the tetramers are fully helical as determined by CD. The four-chain coiled-coils are well folded as judged by the cooperativity of thermal unfolding and by the extent of dispersion in aliphatic chemical shifts seen in NMR spectra. In addition, we measured the chain length dependence of this four-chain coiled-coil. To this end, we developed a general procedure for nonlinear curve fitting of denaturation data in oligomeric systems. The dissociation constants for bundles that contain alpha-helical chains 21, 28, and 35 amino acids in length are 3.1 x 10(-12), 6.7 x 10(-23), and 1.0 x 10(-38) M3, respectively. This corresponds to tetramer stabilities (in terms of the peptide monomer concentration) of 180 microM, 51 nM, and 280 fM, respectively. Finally, we discuss the rules governing coiled-coil formation in light of the work presented here. PMID- 8520472 TI - Hints on the evolutionary design of a dimeric RNase with special bioactions. AB - Residues P19, L28, C31, and C32 have been implicated (Di Donato A, Cafaro V, D'Alessio G, 1994, J Biol Chem 269:17394-17396; Mazzarella L, Vitagliano L, Zagari A, 1995, Proc Natl Acad Sci USA: forthcoming) with key roles in determining the dimeric structure and the N-terminal domain swapping of seminal RNase. In an attempt to have a clearer understanding of the structural and functional significance of these residues in seminal RNase, a series of mutants of pancreatic RNase A was constructed in which one or more of the four residues were introduced into RNase A. The RNase mutants were examined for: (1) the ability to form dimers; (2) the capacity to exchange their N-terminal domains; (3) resistance to selective cleavage by subtilisin; and (4) antitumor activity. The experiments demonstrated that: (1) the presence of intersubunit disulfides is both necessary and sufficient for engendering a stably dimeric RNase; (2) all four residues play a role in determining the exchange of N-terminal domains; (3) the exchange is the molecular basis for the RNase antitumor action; and (4) this exchange is not a prerequisite in an evolutionary mechanism for the generation of dimeric RNases. PMID- 8520473 TI - Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. AB - The structure of the potassium channel blocker agitoxin 2 was solved by solution NMR methods. The structure consists of a triple-stranded antiparallel beta-sheet and a single helix covering one face of the beta-sheet. The cysteine side chains connecting the beta-sheet and the helix form the core of the molecule. One edge of the beta-sheet and the adjacent face of the helix form the interface with the Shaker K+ channel. The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins. However, agitoxin 2 differs significantly from the other channel blockers in the specificity of its interactions. This study was thus focused on a precise characterization of the surface residues at the face of the protein interacting with the Shaker K+ channel. The rigid toxin molecule can be used to estimate dimensions of the potassium channel. Surface-exposed residues, Arg24, Lys27, and Arg31 of the beta sheet, have been identified from mutagenesis studies as functionally important for blocking the Shaker K+ channel. The sequential and spatial locations of Arg24 and Arg31 are not conserved among the homologous toxins. Knowledge on the details of the channel-binding sites of agitoxin 2 formed a basis for site-directed mutagenesis studies of the toxin and the K+ channel sequences. Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions. PMID- 8520474 TI - Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A. AB - Synthetic peptides patterned after the predicted transmembrane sequence of botulinum toxin A were used as tools to identify an ion channel-forming motif. A peptide denoted BoTxATM, with the sequence GAVILLEFIPEIAI PVLGTFALV, forms cation selective channels when reconstituted in planar lipid bilayers. As predicted, the self-assembled conductive oligomers express heterogeneous single-channel conductances. The most frequent openings exhibit single-channel conductance of 12 and 7 pS in 0.5 M NaCl, and 29 and 9 pS in 0.5 M KCl. In contrast, ion channels are not formed by a peptide of the same amino acid composition as BoTxATM with a scrambled sequence. Conformational energy calculations show that a bundle of four amphipathic alpha-helices is a plausible structural motif underlying the measured pore properties. These studies suggest that the identified module may play a functional role in the ion channel-forming activity of intact botulinum toxin A. PMID- 8520475 TI - Escherichia coli alkaline phosphatase: X-ray structural studies of a mutant enzyme (His-412-->Asn) at one of the catalytically important zinc binding sites. AB - The X-ray structure of a mutant version of Escherichia coli alkaline phosphatase (H412N) in which His-412 was replaced by Asn has been determined at both low ( Zn) and high (+Zn) concentrations of zinc. In the wild-type structure, His-412 is a direct ligand to one of the two catalytically critical zinc atoms (Zn1) in the active site. Characterization of the H412N enzyme in solution revealed that the mutant enzyme required high concentrations of zinc for maximal activity and for high substrate and phosphate affinity (Ma L, Kantrowitz ER, 1994, J Biol Chem 269:31614-31619). The H412N enzyme was also inhibited by Tris, in contrast to the wild-type enzyme, which is activated more than twofold by 1 M Tris. To understand these kinetic properties at the molecular level, the structure of the H412N (+Zn) enzyme was refined to an R-factor of 0.174 at 2.2 A resolution, and the structure of the H412N(-Zn) enzyme was refined to an R-factor of 0.166 at a resolution of 2.6 A. Both indicated that the Asn residue substituted for His-412 did not coordinate well to Zn1. In the H412N(-Zn) structure, the Zn1 site had very low occupancy and the phosphate was shifted by 1.8 A from its position in the wild type structure. The Mg binding site was also affected by the substitution of Asn for His-412. Both structures of the H412N enzyme also revealed a surface accessible cavity near the Zn1 site that may serve as a binding site for Tris.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520476 TI - C-terminal specific protein degradation: activity and substrate specificity of the Tsp protease. AB - The activity of Tsp, a periplasmic endoprotease of Escherichia coli, has been characterized by assaying the cleavage of protein and peptide substrates, determining the cleavage sites in several substrates, and investigating the kinetics of the cleavage reaction. Tsp efficiently cleaves substrates that have apolar residues and a free alpha-carboxylate at the C-terminus. Tsp cleaves its substrates at a discrete number of sites but with rather broad primary sequence specificity. In addition to preferences for residues at the C-terminus and cleavage sites, Tsp displays a preference for substrates that are not stably folded: unstable variants of Arc repressor are better substrates than a hyperstable mutant, and a peptide with little stable structure is cleaved more efficiently than a protein substrate. These data are consistent with a model in which Tsp cleavage of a protein substrate involves binding to the C-terminal tail of the substrate, transient denaturation of the substrate, and then recognition and hydrolysis of specific peptide bonds. PMID- 8520477 TI - The optimization of protein-solvent interactions: thermostability and the role of hydrophobic and electrostatic interactions. AB - Protein-solvent interactions were analyzed using an optimization parameter based on the ratio of the solvent-accessible area in the native and the unfolded protein structure. The calculations were performed for a set of 183 nonhomologous proteins with known three-dimensional structure available in the Protein Data Bank. The dependence of the total solvent-accessible surface area on the protein molecular mass was analyzed. It was shown that there is no difference between the monomeric and oligomeric proteins with respect to the solvent-accessible area. The results also suggested that for proteins with molecular mass above some critical mass, which is about 28 kDa, a formation of domain structure or subunit aggregation into oligomers is preferred rather than a further enlargement of a single domain structure. An analysis of the optimization of both protein-solvent and charge-charge interactions was performed for 14 proteins from thermophilic organisms. The comparison of the optimization parameters calculated for proteins from thermophiles and mesophiles showed that the former are generally characterized by a high degree of optimization of the hydrophobic interactions or, in cases where the optimization of the hydrophobic interactions is not sufficiently high, by highly optimized charge-charge interactions. PMID- 8520478 TI - Structural energetics of barstar studied by differential scanning microcalorimetry. AB - The energetics of barstar denaturation have been studied by CD and scanning microcalorimetry in an extended range of pH and salt concentration. It was shown that, upon increasing temperature, barstar undergoes a transition to the denatured state that is well approximated by a two-state transition in solutions of high ionic strength. This transition is accompanied by significant heat absorption and an increase in heat capacity. The denaturational heat capacity increment at approximately 75 degrees C was found to be 5.6 +/- 0.3 kJ K-1 mol-1. In all cases, the value of the measured enthalpy of denaturation was notably lower than those observed for other small globular proteins. In order to explain this observation, the relative contributions of hydration and the disruption of internal interactions to the total enthalpy and entropy of unfolding were calculated. The enthalpy and entropy of hydration were found to be in good agreement with those calculated for other proteins, but the enthalpy and entropy of breaking internal interactions were found to be among the lowest for all globular proteins that have been studied. Additionally, the partial specific heat capacity of barstar in the native state was found to be 0.37 +/- 0.03 cal K-1 g 1, which is higher than what is observed for most globular proteins and suggests significant flexibility in the native state. It is known from structural data that barstar undergoes a conformational change upon binding to its natural substrate barnase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520479 TI - Control of aggregation in protein refolding: a variety of surfactants promote renaturation of carbonic anhydrase II. AB - The denaturation and renaturation of carbonic anhydrase II (CAII) has been studied in several laboratories. Both thermodynamic and kinetic evidence support the existence of at least two intermediates between denatured and native protein. Previous studies have shown that on rapid dilution of a CAII solution from 5 M to 1 M guanidinium chloride, aggregation strongly competes with renaturation at higher protein concentrations, suggesting an upper limit for [CAII] of approximately 0.1%. Our experiments show 60% renaturation at 0.4% [CAII] and that aggregate formation is partially reversible. This yield can be substantially increased by several surfactant additives, including simple alkanols as well as micelle-forming surfactants. Effective surfactants (promoters) act by suppressing initial aggregate formation, not by dissolving aggregates. Promoters act on either the first folding intermediate (I1) or oligomers thereof. Eight of the 18 surfactants examined showed promoter activity, and no correlation was evident between promoter activity and chemical structure or surface tension lowering. These results indicate discrimination (molecular recognition) by I1 and/or its oligomers. PMID- 8520480 TI - Urea-induced dissociation and unfolding of dodecameric glutamine synthetase from Escherichia coli: calorimetric and spectral studies. AB - Urea-induced dissociation and unfolding of manganese.glutamine synthetase (Mn.GS) have been studied at 37 degrees C (pH 7) by spectroscopic and calorimetric methods. In 0 to approximately 2 M urea, Mn.GS retains its dodecameric structure and full catalytic activity. Mn.GS is dissociated into subunits in 6 M urea, as evidenced by a 12-fold decrease in 90 degrees light scattering and a monomer molecular weight of 51,800 in sedimentation equilibrium studies. The light scattering decrease in 4 M urea parallels the time course of Trp exposure but occurs more rapidly than changes in secondary structure and Tyr exposure. Early and late kinetic steps appear to involve predominantly disruption of intra-ring and inter-ring subunit contacts, respectively, in the layered hexagonal structure of Mn.GS. The enthalpies for transferring Mn.GS into urea solutions have been measured by titration calorimetry. After correcting for the enthalpy of binding urea to the protein, the enthalpy of dissociation and unfolding of Mn.GS is 14 +/ 4 cal/g. A net proton uptake of approximately 50 H+/dodecamer accompanies unfolding reactions. The calorimetric data are consistent with urea binding to multiple, independent sites in Mn.GS and the number of binding sites increasing approximately 9-fold during the protein unfolding. PMID- 8520481 TI - Kinetics of interaction of partially folded proteins with a hydrophobic dye: evidence that molten globule character is maximal in early folding intermediates. AB - Interaction with 8-anilino-1-naphthalenesulfonate (ANS) is widely used to detect molten globule states of proteins. We have found that even with stable partially folded states, the development of the fluorescence enhancements resulting from such interactions can be relatively slow and kinetically complex. This is probably because initial binding of the dye can induce subsequent changes in the protein structure, so that the ultimate resulting fluorescence enhancement is not necessarily a good, nonperturbing probe of the preexisting state of the protein. When ANS is used to study folding mechanisms the problem is compounded by the difficulty of distinguishing effects due to the development of dye interactions from those due to the changing populations of folding intermediates. Many of these complications can be avoided by experiments where the ANS is introduced only after folding has been allowed to proceed for a variable time. The initial fluorescence intensity after mixing, resulting only from rapid and therefore hopefully relatively nonperturbing interactions with the protein, can be monitored at different refolding times to provide a better reflection of the progress of the reaction, uncomplicated by dye interaction effects. Such studies of the folding of carbonic anhydrase and alpha-lactalbumin have been compared with conventional single-mix experiments and large discrepancies observed. When ANS was present throughout refolding, time-dependent changes attributed to the formation or reorganization of protein-ANS complexes were clearly superimposed on those associated with the actual progress of refolding, and the folding kinetics and population of intermediates were also substantially perturbed by the dye. Thus, it is clear that the pulse method, though cumbersome, should be used where refolding reactions are to be probed by dye binding. The results emphasize that fluorescence enhancement tends to be greatest in early intermediates, in contrast to what, for carbonic anhydrase at least, might appear to be the case from the more conventional experiments. Later intermediates in the folding of both of these proteins actually induce little fluorescence enhancement and therefore may be quite different in nature from equilibrium molten globule states. PMID- 8520482 TI - Characterization of leucine zipper complexes by electrospray ionization mass spectrometry. AB - The development of "soft" ionization methods has enabled the mass spectrometric analysis of higher-order structural features of proteins. We have applied electrospray ionization mass spectrometry (ESI-MS) to the analysis of the number and composition of polypeptide chains in homomeric and heteromeric leucine zippers. In comparison with other methods that have been used to analyze leucine zippers, such as analytical ultracentrifugation, gel chromatography, or electrophoretic band shift assays, ESI-MS is very fast and highly sensitive and provides a straightforward way to distinguish between homomeric and heteromeric coiled-coil structures. ESI-MS analyses were carried out on the parallel dimeric leucine zipper domain GCN4-p1 of the yeast transcription factor GCN4 and on three synthetic peptides with the sequences Ac-EYEALEKKLAAX1EAKX2QALEKKLEALEHG-amide: peptide LZ (X1, X2 = Leu), peptide LZ(12A) (X1 = Ala, X2 = Leu), and peptide LZ(16N) (X1 = Leu, X2 = Asn). Equilibrium ultracentrifugation analysis showed that LZ forms a trimeric coiled coil and this could be confirmed unequivocally by ESI-MS as could the dimeric nature of GCN4-p1. The formation of heteromeric two- and three-stranded leucine zippers composed of chains from LZ and LZ(12A), or from GCN4-p1 and LZ, was demonstrated by ESI-MS and confirmed by fluorescence quenching experiments on fluorescein-labeled peptides. The results illustrate the adaptability and flexibility of the leucine zipper motif, properties that could be useful to the design of specific protein assemblies by way of coiled-coil domains. PMID- 8520483 TI - Establishing isostructural metal substitution in metalloproteins using 1H NMR, circular dichroism, and Fourier transform infrared spectroscopy. AB - Far-UV CD, 1H-NMR, and Fourier transform infrared (FTIR) spectroscopy are three of the most commonly used methods for the determination of protein secondary structure composition. These methods are compared and evaluated as a means of establishing isostructural metal substitution in metalloproteins, using the crystallographically defined rubredoxin from Desulfovibrio gigas and its well characterized cadmium derivative as a model system. It is concluded that analysis of the FTIR spectrum of the protein amide I resonance represents the most facile and generally applicable method of determining whether the overall structure of a metalloprotein has been altered upon metal reconstitution. This technique requires relatively little biological material (ca. 300 micrograms total protein) and, unlike either CD or 1H-NMR spectroscopy, is unaffected by the presence of different metal ions, thus allowing the direct comparison of FTIR spectra before and after metal substitution. PMID- 8520484 TI - The distribution of alpha-helix propensity along the polypeptide chain is not conserved in proteins from the same family. AB - We address the question of whether the distribution of secondary structure propensities of the residues along the polypeptide chain (denominated here as secondary structure profiles) is conserved in proteins throughout evolution, for the particular case of alpha-helices. We have analyzed by CD the conformation of peptides corresponding to the five alpha-helices of two alpha/beta parallel proteins (ComA and Ara). The large alpha-helical population of peptide ComA-4 detected by CD in aqueous solution has been confirmed by NMR. These proteins are members of the CheY and P21-ras families, respectively, which have been studied previously in the same way (Munoz V, Jimenez MA, Rico M, Serrano L, 1995, J Mol Biol 245:275-296). Comparison of the helical content of equivalent peptides reveals that protein alpha-helix propensity profiles are not conserved. Some equivalent peptides show very different helical populations in solution and this is especially evident in very divergent proteins (ComA and CheY). However, all the peptides analyzed so far adopted an important population of helical conformations in the presence of 30% trifluoroethanol, indicating that there could be a conserved minimal requirement for helical propensity. PMID- 8520485 TI - Finding flexible patterns in unaligned protein sequences. AB - We present a new method for the identification of conserved patterns in a set of unaligned related protein sequences. It is able to discover patterns of a quite general form, allowing for both ambiguous positions and for variable length wildcard regions. It allows the user to define a class of patterns (e.g., the degree of ambiguity allowed and the length and number of gaps), and the method is then guaranteed to find the conserved patterns in this class scoring highest according to a significance measure defined. Identified patterns may be refined using one of two new algorithms. We present a new (nonstatistical) significance measure for flexible patterns. The method is shown to recover known motifs for PROSITE families and is also applied to some recently described families from the literature. PMID- 8520486 TI - Predicting oligomerization states of coiled coils. AB - An algorithm based on the profile method was developed that faithfully distinguishes between the amino acid sequences of dimeric and trimeric coiled coils. Normalized sequence profiles derived from nonhomologous, two- and three stranded, coiled-coil sequences with unambiguous registers were used to assign dimer and trimer propensities to test sequences. The difference between the dimer and trimer profile scores accurately reflected the preferred oligomerization state. The method relied on two strategies that may be generally applicable to profile calculations--profile values of solvent-exposed residues and of amino acids that were underrepresented in the data-base were given zero weight. Differences between the dimer and trimer profiles revealed sequence patterns that match and extend experimental studies of oligomer specification. PMID- 8520488 TI - Gibbs motif sampling: detection of bacterial outer membrane protein repeats. AB - The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID- 8520487 TI - Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs. AB - Computer-assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins GCD6 and GCD1, and mammalian homolog of GCD6-subunits of the eukaryotic translation initiation factor eIF-2B involved in GDP/GTP exchange on eIF-2. It is shown that these proteins contain a putative nucleotide-binding domain related to a variety of nucleotidyltransferases, most of which are involved in nucleoside diphosphate sugar formation in bacteria. Three conserved motifs, one of which appears to be a variant of the phosphate-binding site (P-loop) and another that may be considered a specific version of the Mg(2+)-binding site of NTP-utilizing enzymes, were identified in the nucleotidyltransferase-related domain. Together with the third unique motif adjacent to the the P-loop, these motifs comprise the signature of a new superfamily of nucleotide-binding domains. A domain consisting of hexapeptide amino acid repeats with a periodic distribution of bulky hydrophobic residues (isoleucine patch), which previously have been identified in bacterial acetyltransferases, is located toward the C-terminus from the nucleotidyltransferase-related domain. Finally, at the very C-termini of GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5, there is a previously undetected, conserved domain. It is hypothesized that the nucleotidyltransferase-related domain is directly involved in the GDP/GTP exchange, whereas the C-terminal conserved domain may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2. PMID- 8520489 TI - Pseudotorsional OCCO backbone angle as a single descriptor of protein secondary structure. AB - Protein secondary structure is conventionally identified using characteristic ranges of two backbone torsional angles phi and psi. We suggest that the secondary structure can be adequately characterized by a single descriptor, the Oi-1Ci-1CiOi (where i is the residue number) pseudotorsional backbone angle. A set of 102 structurally distinct protein chains from the Protein Data Bank was used to evaluate the adequacy of this descriptor. We find that a specific range of OCCO angles corresponds to each major secondary structure. The complete range of OCCO angles (-180 degrees to 179 degrees) was broken into 18 consecutive subranges of 20 degrees each, and each subrange was assigned a letter. Thus, the OCCO profiles for each protein in the database were "translated" into a sequence of letters. The Needleman-Wunsch primary sequence alignment algorithm was then used for secondary/tertiary structure comparison and alignment. Preliminary results indicate that this new approach has a significant potential for rapid identification of fold families in the Protein Data Bank. PMID- 8520490 TI - Molecular model of the N-terminal receptor-binding domain of the human CD6 ligand ALCAM. AB - CD6-ligand interactions have been implicated in the regulation of T-cell adhesion and activation. CD6 is a member of the scavenger receptor family, whereas its human ligand (ALCAM) belongs to the immunoglobulin superfamily. The extracellular region of ALCAM includes five immunoglobulin-like domains. As a fusion protein, the N-terminal extracellular domain of ALCAM (ALCAMD1) binds specifically to CD6. We report the construction, assessment, and analysis of a molecular model of ALCAMD1. The model defines the CDR-analogous loops, the location of N-linked glycosylation sites, and residues that form the beta-sheet faces of the immunoglobulin-like domain. Predicted structural characteristics of the A'GFCC'C" face of the model are consistent with the presence of monomeric and dimeric forms of ALCAMD1, which has implications for the receptor-ligand interactions. PMID- 8520491 TI - Purification and preliminary X-ray crystallographic studies of recombinant L ribulose-5-phosphate 4-epimerase from Escherichia coli. AB - The araD gene from Escherichia coli, coding for L-ribulose-5-phosphate 4 epimerase, was overexpressed and the resulting enzyme was purified to homogeneity. Crystals of L-ribulose-5-phosphate 4-epimerase, obtained with 4.0 M sodium formate as precipitant, belong to space group P4212 with unit cell dimensions a = b = 107.8 A and c = 281.4 A and diffract to at least 2.2 A resolution. Density measurements of these crystals are consistent with eight subunits in the asymmetric unit. PMID- 8520492 TI - Crystallization of the chaperone protein SecB. AB - The secretory protein SecB found in Escherichia coli is a molecular chaperone that binds to precursor forms of a number of proteins targeted for export to the periplasmic space. SecB maintains these proteins in a translocation-competent conformation facilitating the translocation process. The material has been cloned and expressed in E. coli. Crystals have been grown from polyethylene glycol 8000 by vapor diffusion using the hanging drop technique. These crystals are monoclinic, belonging to space group C2 with unit cell dimensions a = 56.0 A, b = 111.1 A, c = 134.7 A, and beta = 104 degrees. The crystals diffract to 8 A resolution on a Rigaku imaging plate detector. Dynamic light scattering experiments suggest that SecB exhibits aggregation behavior with a number of different precipitating agents. These results may explain resistance of SecB to forming ordered crystals. PMID- 8520493 TI - Crystallization and preliminary X-ray analysis of electron transfer flavoproteins from human and Paracoccus denitrificans. AB - Mammalian electron transfer flavoprotein (ETF) is a soluble, heterodimeric flavoprotein responsible for the oxidation of at least nine primary matrix flavoprotein dehydrogenases. Crystals have been obtained for the recombinant human electron transfer flavoprotein (ETFhum) by the sitting-drop vapor diffusion technique using polyethylene glycol (PEG) 1500 at pH 7.0 as the precipitating agent. ETFhum crystallizes in the monoclinic space group P2(1), with unit cell parameters a = 47.46 angstrum, b = 104.10 angstrum, c = 63.79 angstrum, and beta = 110.02 degrees. Based on the assumption of one alpha beta dimer per asymmetric unit, the Vm value is 2.69 angstrum 3/Da. A native data set has been collected to 2.1 angstrum resolution. One heavy-atom derivative has also been obtained by soaking a preformed crystal of ETFhum in 2 mM thimerosal solution for 2h at 19 degrees C. Patterson analysis indicates one major site. The analogous electron transfer flavoprotein from Paracoccus denitrificans (ETFpar) has also been crystallized using PEG 8000 at pH 5.5 as the precipitating agent. ETFpar crystallizes in the orthorhombic space group P2(1)2(1)2(1), with unit cell parameters a = 79.98 angstrum, b = 182.90 angstrum, and c = 70.07 angstrum. The Vm value of 2.33 angstrum 3/Da is consistent with two alpha beta dimers per asymmetric unit. A native data set has been collected to 2.5 angstrum resolution. PMID- 8520494 TI - Crystallization and preliminary X-ray diffraction studies of the human adenovirus serotype 2 proteinase with peptide cofactor. AB - Recombinant human adenovirus serotype 2 proteinase (both native and selenomethionine-substituted) has been crystallized in the presence of the serotype 12, 11-residue peptide cofactor. The crystals (space group P3(1)21 or P3(2)21, one molecule per asymmetric unit, a = b = 41.3 angstrum, c = 197.0 angstrum) grew in solutions containing 20-40% 2-methyl-2,4-pentanediol (MPD), 0.1 0.2 M sodium citrate, and 0.1 M sodium HEPES, pH 5.0-7.5. Diffraction data (84% complete to 2.2 angstrum resolution with Rmerge of 0.0335) have been measured from cryopreserved native enzyme crystals with the Argonne blue (1,024 x 1,024 pixel array) charge-coupled device detector at beamline X8C at the National Synchrotron Light Source (operated by Argonne National Laboratory's Structural Biology Center). Additionally, diffraction data from selenomethionine-substituted proteinase, 65% complete to 2.0 angstrum resolution with Rmerge values ranging 0.05-0.07, have been collected at three X-ray energies at and near the selenium absorption edge. We have determined three of the six selenium sites and are initiating a structure solution by the method of multiwavelength anomalous diffraction phasing. PMID- 8520495 TI - The incidence and epidemiology of plasma cell neoplasms. AB - Plasma cell neoplasia includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and Waldenstrom's macroglobulinemia (WM). In MGUS, a large, stable clone does not cause symptoms; additional change(s) is/are required to convert this clone into a progressively expanding tumor that becomes symptomatic, as in MM or WM. The prevalence of MGUS (i.e., the number of cases in a defined population at a certain time) is 20 times greater than MM. The incidence (i.e., the number of cases developing in a defined population in a defined period) has not been determined for MGUS. Between 1960 and 1969, the average, annual, age-adjusted (1950 standard) incidence of MM in Malmo, Sweden was 3.4/10(5). The incidence of MM is strongly influenced by the age and race of the population, and the diagnostic services available. MM is a disease of old age; it rarely occurs before the age of 40. The incidence of MM increases rapidly with age, is lowest among the Chinese and Japanese, intermediate among Caucasians in America and Europe, and highest among blacks in the USA. The striking differences in the incidence of MM in different countries appears to be due to racial rather than environmental differences, since the low incidence among the Chinese and Japanese in Asia has migrated with them to the Bay area of California and to Hawaii. The high incidence of MM in USA black males (10.8/10(5)) and females (7.2/10(5)) is more than twice the rate for whites in the same regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520496 TI - Pathogenetic relation between monoclonal gammopathies of undetermined significance and multiple myeloma. AB - Plasma cell atypia and cell proliferation changes which occur during the progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are accompanied by critical changes in neoplastic plasma cells and marrow stromal cells. Key elements include paracrine secretion of interleukin 6 (IL-6) by marrow stromal cells resulting from interleukin 1 beta (IL-1 beta) secreted by myeloma cells. In addition, there are stable elevated levels of serum soluble IL-6 receptor (sIL-6R) in MM and MGUS. They are higher than levels seen in normals. Oncogenes such as c-myc and ras probably play a major role as do cell adhesion molecules and loss of apoptosis. Immune regulatory cells may also play a role. A key element yet to be clearly defined is delineating the role of circulating plasma cells and their precursors in spreading the disease. PMID- 8520497 TI - Is alpha-interferon treatment in multiple myeloma worthwhile? AB - The article reviews the therapeutic efficacy of alpha interferon (alpha IFN) in the management of myelomatosis. The data provided in the medical literature suggest that alpha IFN is a useful agent in the management of myelomatosis. In particular, its association to conventional induction therapies of previously untreated multiple myeloma (MM) patients may improve the overall response rate and probably increase the number of complete responders. On the other hand, even though alpha IFN alone, in some patients with previously untreated MM, may induce good objective responses, it remains certainly less effective than conventional chemotherapy. Moreover, in a small proportion of advanced MM patients, alpha IFN alone has induced objective responses. It is therefore possible that alpha IFN should be combined with other therapeutic modalities to improve the observed response rate in these patients. Finally, alpha IFN maintenance treatment seems to be one of the most promising therapies for patients with myelomatosis. However, the achievement of a "true" "plateau phase" after the induction treatment is certainly necessary to permit alpha IFN of prolonging the response duration as well as survival duration. The importance of the achievement of a "true" "plateau phase" is better emphasized by the good results obtained using alpha IFN after transplantation procedures. PMID- 8520498 TI - Maintenance therapy for remission in myeloma with Intron A following high-dose melphalan and either an autologous bone marrow transplantation or peripheral stem cell rescue. AB - Eighty-four patients with myeloma were randomized to receive maintenance Intron A (Schering-Plough, Suffolk, UK), 3 mega units/m2 s.c. three times weekly or no treatment following induction therapy with cyclophosphomide, vincristine, doxorubicin, methyl prednisolone (C-VAMP), consolidated with high-dose melphalan (HDM) 200 mg/m2 + autologous bone marrow transplantation (ABMT). The patients have been followed up for a median of 52 months. Overall, median progression-free survival (PFS) from HDM was 27 months in the control group and 46 months in the Intron A group (< 0.025). For the 65 patients who achieved complete remission (CR) with HDM, there was a significant prolongation of remission (p = 0.02) for those who received Intron A and 49% of these patients remained in remission four years after high-dose treatment. However, for partial responders (PR) and nonresponders to HDM there was no significant prolongation of PFS. Overall, survival was also significantly better for the Intron A group, with 5 deaths versus 14 deaths in the control group (p = 0.006). Subsequently, 54 consecutive patients received the same HDM followed by rescue with peripheral blood stem cells after induction chemotherapy which included C-VAMP. Intron A was started in 45 of these patients at a median of 62 days which was comparable to the ABMT arm. The overall response rate in these patients was 79.62% (43/54-CR+PR) and the probability of survival at 18 months was 74.2% by the Kaplan Meier method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520499 TI - Myeloablative therapy for primary resistant multiple myeloma. AB - Myeloablative therapy supported by autologous bone marrow or blood stem cell transplantation was assessed in 41 patients who had multiple myeloma resistant to vincristine-doxorubicin by continuous infusion with high-dose dexamethasone (VAD) or other high-dose dexamethasone regimens. In patients who had high or intermediate tumor mass, the myeloma cell mass was reduced by more than 75% in 56% of patients and the survival time quadrupled in comparison with that of a matched control group. Later treatment resulted in a lower response rate and shorter remission. Current myeloablative regimens supported by autologous stem cells provided a useful treatment for patients who had advanced primary resistant multiple myeloma. Such treatment should be given early in the disease course to provide the best chance for remission, collecting blood stem cells with facility, and preventing complications that would increase the risk of the procedure. PMID- 8520500 TI - An update of prognostic factors for allogeneic bone marrow transplantation in multiple myeloma using matched sibling donors. European Group for Blood and Marrow Transplantation. AB - Analysis of prognostic factors has been made in 369 allogeneic transplants for multiple myeloma reported to the registry of the European Group for Blood and Bone Marrow Transplantation (EBMT). Favorable prognostic factors for obtaining a complete remission (CR) were stage I at diagnosis (CR 77%), one line of treatment before conditioning (CR 52%), CR before conditioning (CR 60%), and Ig A or light chain myeloma (CR 43% and 42%). Factors that predicted significantly for favorable survival in a univariate analysis included having received only one line of treatment, female sex, stage I at diagnosis, stage I at conditioning and a beta 2-Microglobulin less than 4 mg/l. Favorable post-BMT factors consisted of obtaining a CR following BMT and not being in graft-versus-host disease stage III or IV. A multivariate analysis of pre-BMT factors showed that the sex of the patient and the number of lines of treatment pretransplant were independent prognostic factors. Allogeneic BMT is a promising treatment method for patients who have received only one line of treatment, particularly if they are of the female sex. BMT late in the course of the disease is usually unsuccessful. PMID- 8520501 TI - Allogeneic bone marrow transplantation for the treatment of multiple myeloma. An overview of published reports. AB - Allogeneic bone marrow transplantation (BMT) was first explored for the treatment of multiple myeloma (MM) in the mid 1980s. Since then, there has been a rapidly growing clinical demand for the use of this modality of treatment, so that the number of patients receiving worldwide transplants from HLA-identical siblings is actually estimated to be at least several hundreds. Although it is difficult to compare results between different centers because of differences in patient characteristics, selection criteria for transplantation and conditioning regimens, a certain number of conclusions have emerged from these experiences. There is evidence that allogeneic BMT performed in different phases of MM and with different conditioning regimens yields a high frequency of complete remissions (CR), in the range of 50% to 60%, and long-term survival and remission rates, both averaging approximately 20%. Although a toxic-related mortality rate of 40% has been consistently reported for many years, the outcome of patients in whom BMT was performed as consolidation of remission has recently improved. Prior responsiveness to conventional chemotherapy, also the presence of low tumor cell mass (both at diagnosis and before transplant) predicts for increased CR rate (up to 70% or more), as well as long-term survival and remission rates (both averaging approximately 50%). The continued relapse-free survival, up to and beyond ten years, reported for some of these patients provides strong evidence that allogeneic BMT has the potential ability to cure MM, probably as the result of an immunologic effect of the infused donor's marrow T lymphocytes against residual myeloma cells (graft-versus-myeloma).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520502 TI - Autologous stem cell transplantation after first remission induction treatment in multiple myeloma. A report of the French Registry on Autologous Transplantation in Multiple Myeloma. AB - Eighteen French centers reported 133 autologous stem cell transplantations performed after first remission induction in multiple myeloma. The source of stem cell was marrow (81 cases), blood (51 cases) or marrow plus blood (1 case). The immediate outcome after transplantation was 49 (37%) complete remissions (CR; 13 maintained, 36 achieved), 61 (46%) partial remissions, 17 failures and 5 toxic deaths. With a median follow up of 35 months, the median remission duration was 33 months, the median time to treatment failure was 22 months. The median overall survival was 46 months, 54 months for the 103 patients responding to primary treatment and 30 months for the 30 nonresponders. In univariate analysis, the outcome was influenced by age, Ig isotype, initial beta 2-Microglobulin level, response to initial chemotherapy, plasma cell marrow involvement at the time of harvest, albumin and beta 2-Microglobulin level at the time of transplantation and CR achievement after transplantation. In multivariate analysis, the most important prognostic factor was the quality of response after transplantation. The conditioning regimen and the source of stem cell had no significant impact on immediate and long-term results. Maintenance therapy with alpha interferon did not appear to prolong remission duration or survival. Autologous stem cell transplantation is an effective consolidation for patients responding to primary treatment and a salvage therapy for some nonresponding patients. This approach has to be compared to conventional chemotherapy in prospective randomized studies. The critical impact of CR achievement on survival implies new strategies in order to increase the CR rate. PMID- 8520503 TI - Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation. AB - Autologous hematopoietic stem cell transplantation was used for treatment of 384 patients with multiple myeloma in 37 centers during the years 1986-1994. An analysis of prognostic factors was performed in 207 of these patients. One hundred forty one were males and 66 females, and median age was 49 years (range, 24-68). Actuarial survival at 78 months is 45%. Factors associated with a good prognosis were: response on chemotherapy immediately pretransplant, administration of only one treatment regimen, a low serum-beta 2-Microglobulin value at diagnosis and the use of a conditioning regimen including melphalan. In a multivariate analysis, response status pretransplant, age < 45 years, melphalan conditioning and non-TBI conditioning were independently predictive for longer survival, while transplantation after only one line of primary treatment and isotype other than light-chain were of borderline significance. Post-transplant alpha-interferon treatment was associated with improved survival in responsive patients. Eighteen patients treated in one center (Huddinge) passed a double autograft program, and 14 are in continuous complete remission ([CR]; n = 10) or good partial remission (n = 4) at a median time of 17 months after the first transplant (range, 2-38). In five CR patients, polymerase chain reaction (PCR) analysis of the clone-specific immunoglobulin-rearrangement was performed, and four are PCR-negative up to 33+ months after the first transplantation. We conclude that autografting in myeloma is most effective when applied early in the course of disease in younger, chemotherapy-reponsive patients. Alpha-interferon maintaince treatment seems to be beneficial with respect to improved survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520504 TI - Mobilization of peripheral blood stem cells with chemotherapy and cytokines in multiple myeloma. AB - In an attempt to offset the impaired hematopoietic progenitors' mobilization and collection which are frequently encountered in multiple myeloma (MM), we have started a pilot study to evaluate the ability of a combination of high-dose melphalan (HDM) and sequential s.c. administration of recombinant human interleukin 3 (rhIL-3) and rh-granulocyte colony-stimulating factor (G-CSF) to mobilize blood cells (BC) in MM patients. Two different schedules for administration were successively tested. Schedule A consisted of IL-3 (5 micrograms/kg/d) from day 7 to day 11 after HDM followed by G-CSF (5 micrograms/kg/d) from day 12 to day 20. Under schedule B, HDM was followed by IL 3 alone at the same dosage from day 1 to day 3, IL-3 and G-CSF (idem) from day 4 to day 7 and G-CSF alone from day 8 until completion of apheresis. Two patients (one previously untreated, one having received prior chemotherapy for one year) underwent schedule A; three patients (one previously untreated, two pretreated) underwent schedule B. The post-HDM aplasia was not shortened in schedule A patients in comparison to what we usually observed following HDM alone (25 days) correlated with a very moderate two- to three-fold CD34+ cell increase. Only one patient was further transplanted with apheresis products: the post-transplant granulocyte recovery was slower than usual (16 days versus 12 days) while platelet count never recovered over 20 x 10(9)/l. In contrast, the post-HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520505 TI - High-dose therapy and autologous blood stem cell transplantation in multiple myeloma: preliminary results of a randomized trial involving 167 patients. AB - Since 1986, we have treated young patients with aggressive multiple myeloma (MM) by high-dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow up of five years after transplantation, overall survival was 60% and median event free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy-mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high-dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders. As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p = 0.28, two-sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group. ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520506 TI - Autologous blood progenitor cell transplantation in high-risk multiple myeloma. AB - The aim of the study was to evaluate the feasibility and the efficacy of high dose chemoradiotherapy followed by autologous hematopoietic stem cell support with peripheral blood progenitor cells (PBPC) harvested after high-dose cyclophosphamide (HDCYC) treatment in patients with high-risk multiple myeloma (MM). Inclusion criteria were: age less than 65 years and high-risk MM defined as stage II MM, stage III MM, refractory or relapsed MM. The design of the study was: 1) HDCYC +/- hematopoietic growth factors followed by PBPC collection, and 2) high-dose melphalan combined with total body irradiation (or busulfan for previously irradiated patients) followed by PBPC reinfusion (ABPCT). All 60 patients completed the procedure except two who died from infection after HDCYC and another of acute cardiac failure after reinfusion of PBPC. Out of the 60 evaluable patients, three failed to respond while the other 57 achieved either a partial (n = 33) or complete (n = 24) response. Thirty-one patients progressed or relapsed after a median duration of response of 15 months (range: 3-43). The median follow-up for the other 26 responder patients was 24 months (range: 2-66). Twenty-one patients died, 18 of MM (2 after failure, 16 after relapse) and three responders of lung cancer (n = 1) and infection (n = 2). In conclusion, this study shows that this therapeutic approach is feasible and efficient. PMID- 8520507 TI - Homing mechanisms in the etiopathogenesis of multiple myeloma. AB - Although multiple myeloma (MM) is characterized by a monoclonal expansion of plasma cells, it has been assumed that the tumor clone also includes more immature B cells. We could demonstrate by DNA sequence analysis of the variable region in immunoglobulin (Ig) heavy chain genes, that myeloma patients have peripheral blood monoclonal B cells that have not switched their Ig isotype but are somatically hypermutated. This finding suggests that myeloma originates from a germinal center B cell of the lymph node, most probably a memory B cell or B lymphoblast. The identification of these cells in the peripheral blood circulation implies that they must be equipped with homing receptors that allow them to migrate from the lymph node to the marrow environment. Within the marrow compartment these precursors will receive the appropriate differentiation signals to become mature tumor cells. The growth and survival of these bone marrow (BM) plasma cells is believed to be regulated by a functional interplay with the surrounding marrow stroma involving different adhesive mechanisms and the action of several cytokines. We found that myeloma plasma cells express several adhesion molecules (ICAM-1, N-CAM, CD44, VLA-4). Myeloma cell lines can bind to purified fibronectin (FN) using mostly the VLA-4 receptor. However this interaction contributes only partially to binding with intact stromal layers. In contrast, the post-HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520508 TI - An interleukin 1 receptor antagonist blocks the IL-1-induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma. AB - By analogy with the model of pristane-induced mouse plasmacytomas, we have wondered about the putative role of prostaglandin E2 (PGE2) in the human multiple myeloma (MM) cytokine network, involving interleukin 6 (IL-6) and interleukin 1 (IL-1) as essential myeloma cell growth factors and inducing cofactors respectively. We show that PGE2 is produced in short-term cultures of bone marrow cells of patients with MM, concomitantly with both IL-6 and IL-1. Indomethacin, a potent inhibitor of cyclo-oxygenase and of PGE2 synthesis, significantly inhibits IL-6 production (but not IL-1 production) by 35% to 90% depending on the different MM patients studied and concurrently to that of PGE2. Exogenous PGE2 reverses this inhibition or even stimulates IL-6 production. An IL-1 receptor antagonist (IL-1RA) also significantly inhibits PGE2, IL-6 production and myeloma cell growth. The inhibition of IL-6 production is reversed by adding exogenous PGE2. These results show that induction of IL-6 by IL-1 is related to PGE2 in the bone marrow of patients with MM. Inhibition of PGE2 synthesis (as obtained with indomethacin and the IL-1RA) might be helpful to inhibit myeloma cell proliferation by reducing IL-1-induced endogenous IL-6 production not only in vitro (as demonstrated here) but also in vivo. PMID- 8520509 TI - Regulation of interleukin 6 in multiple myeloma and bone marrow stromal cells. AB - We and others have shown that some freshly isolated multiple myeloma (MM) cells and derived cell lines express interleukin 6 (IL-6) receptors and proliferate in vitro in response to IL-6; a subset of MM cells also expresses IL-6 mRNA, is intracytoplasmic IL-6 positive and secretes IL-6. We have shown that MM cells express the cell surface adhesion molecules CD29/CDw49d(VLA-4), CD18/CD11a(LFA-1) and CD44, and may localize to marrow via specific adherence to both extracellular matrix proteins and to bone marrow stromal cells (BMSCs). MM cell adhesion triggers IL-6 secretion by normal and MM BMSCs and related IL-6-mediated tumor cell growth. Our attempts to block MM cell adhesion to BMSC-induced IL-6 secretion by using antibodies to CD29/CDw49d, CD18/11a, and/or CD44 demonstrated minimal effects, suggesting that another ligand-receptor interaction triggers IL 6 secretion when MM cells and BMSCs are juxtaposed. Both MM cells and BMSCs express CD40. Triggering of MM cells and BMSCs via CD40 upregulates IL-6 secretion in both MM cells and MM-derived cell lines, as well as BMSCs and BMSC lines, suggesting the possibility of both autocrine and paracrine MM cell growth triggered via CD40. Finally, experiments using the LP 101 BMSC line transiently transfected with IL-6 promoter fragments linked to chloramphenicol acetyltransferase reporter gene demonstrate that adhesion of MM cells induces IL 6 gene transcription in BMSCs, which is conferred via the NF-kappa B binding motif.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520510 TI - The mechanisms of bone lesions in human plasmacytomas. AB - Bone involvement, mainly bone destruction, is a characteristic feature of human plasma-cytomas (PCT); on the other hand, it is exceptional in B cell malignancies other than PCT. Bone destruction is the consequence of an uncoupling process (associating an increased osteoclastic resorption with an inhibition of bone formation) and of a marked bone loss. Conversely, patients lacking lytic bone lesions or those with sclerotic PCT have an increased bone resorption but maintain a normal or have an increased bone formation (coupling process). This excessive osteoclastic resorption is an early phenomenon, as opposed to the inhibition of bone formation, and is observed several months or years before the occurrence of the first clinical symptoms of the disease. Thus, it is an early criterion of malignancy, useful for discriminating benign monoclonal gammopathy and smoldering PCT from early active PCT. Several inflammatory cytokines, osteoclast colony-stimulating factors and osteoclast activating factors produced either by the PCT cells themselves or the hematopoietic microenvironment, are probably involved in the pathogenesis of such bone lesions. At the present time, interleukin 6 (IL-6), (a major PCT-cell growth factor), its agonistic receptor gp80, IL-1 beta and tumor necrosis factor-alpha appear to be the most critical factors. Indirect arguments suggest that other hematopoietic growth factors, mainly macrophage colony-stimulating factor, might play a role. Taken together, these data demonstrate a close relationship between PCT-cell growth factors and factors involved in the occurrence of bone lesions. PMID- 8520511 TI - An in vivo model of human multiple myeloma bone disease. AB - Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin G kappa (IgG kappa), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 10(6) ARH 77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemic developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520512 TI - Impeded normal hematopoiesis in bone marrow of patients with multiple myeloma. AB - Insufficient output of mature blood cells frequently accompanies the typical impairments of late B cell development in multiple myeloma (MM). In a large group of previously untreated patients, bone marrow samples were analyzed and showed a general decrease of mononuclear cell (MNC) content. Colony growth of granulo monocytic progenitors in short-term assays is compromised in a substantial number of patients at partly severe degrees, who at the same time show higher plasma cell content and belong to clinically more severe groups; the other patients show normal in vitro growth, contain less plasmocytes in the marrow and belong to varying degrees of aggressiveness. Thus a heterogeneity of the disease is emerging on the level of bone marrow cells which matches with high aggressiveness of the disease in one type. It can be speculated that in this type there are different underlying mutational events compared to the others: besides the characteristic changes in B cell differentiation, here the cellular defects have an impact on normal granulo-monocytic (and other) progenitor recruitment, which is absent in the other cases. PMID- 8520513 TI - Prognostic factors in multiple myeloma. AB - The median duration of survival for patients with multiple myeloma ranges from 2.5 to 3 years. However, there is considerable variability from one patient to another. Renal function as determined from blood urea nitrogen or serum creatinine values, hemoglobin value, calcium level and performance status have been recognized as prognostic factors for more than 20 years. A study of 107 patients with newly diagnosed multiple myeloma at the Mayo Clinic showed that plasma cell labeling index (PCLI); levels of thymidine kinase, beta 2 microglobulin (beta 2-M), serum albumin, and C-reactive protein; and age were all significant univariate prognostic factors. Only PCLI and beta 2-M levels had independent prognostic significance. Among nine patients younger than 65 years with low PCLI and low beta 2-M levels, eight were alive almost six years after starting chemotherapy. Interleukin 6 (IL-6) is a significant univariate predictor of survival in myeloma. An elevated lactate dehydrogenase content is associated with a poor prognosis. An elevated soluble IL-6 receptor (sIL-6R) level is an independent factor associated with shorter survival. In one study, the addition of sIL-6R to PCLI and beta 2-M to the analysis doubled the proportion of patients identified as high-risk. In this study, the two-year survival was 41% at two years if the PCLI was > or = 2%, beta 2-M was > or = 4.0 micrograms/dl, or sIL-6R was > 300 ng/ml. When none of these three factors were increased, the estimated two-year survival was 83%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520514 TI - Chemoresistance and multiple myeloma: from biological to clinical aspects. AB - Resistance to chemotherapy represents a major cause for cancer treatment failure. Several biological mechanisms implicated in chemoresistance have been described, including multidrug resistance (MDR1/P-glycoprotein [P-gp] or p170), resistance related proteins (p95 and p110), multidrug resistance-associated protein (p190), proteins implicated in cell detoxification such as glutathione S-transferase and genes affecting DNA structure (topoisomerases). MDR1 has been the most studied in hematological malignancies, particularly in lymphoma and multiple myeloma (MM), diseases generally considered as overexpressing such mechanisms in relapse. Overexpression of chemoresistance is generally an induced phenomenon caused or amplified by the drugs, as demonstrated by the development of drug-resistant cell lines in vitro. It may be defined as a profile of chemoresistance depending on the drug used for induction. This may have a potential implication for monitoring chemoresistance to modulate or to prevent its amplification. Several questions are always open to discussion, including the method of detection, the true prognostic impact of chemoresistance, the dynamic expression of such mechanisms, depending on the cell status, the host response and the mechanism of induction. In MM, the over-expression of MDR1/P-gp is usually less than 10% at diagnosis, leading to 59-80% at relapse, depending on the clinical status. The percentage of positivity depends on the cumulative dose of vincristine and/or doxorubicin. GST pi is (over)expressed in 10-70% of patients at diagnosis, and in 30% at relapse, but in small series, as well as for topoisomerases I and II which are concerned in 53% and 6%, respectively, at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520515 TI - Tumor-directed cytotoxicity in multiple myeloma--the basis for an experimental treatment approach with interleukin 2. AB - There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be putative targets for immunotherapeutic approaches. Peripheral blood T lymphocytes are capable of suppressing monoclonal immunoglobulin production of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or interleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocytes as demonstrated in a cytotoxicity assay using purified MM plasma cells as targets. The lytic activity is significantly higher when the effectors are prestimulated with irradiated autologous MM plasma cells. Based on these results 18 MM patients of advanced stages with tumor progress received 9 x 10(6) IU/m2 recombinant IL-2 (Proleukin) twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for five subsequent days per week s.c. from days 3-56 (q 12 weeks). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by CD25 antigen expression and CD56+ natural killer (NK) cells expanded in the peripheral blood. NK cell activity and lymphokine-activated killer cell activity were significantly enhanced. IL-2 therapy induced endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations. Tumor response was observed in 6/17 evaluable patients. These data indicate that low-dose IL-2 treatment can stimulate immune enhancement in MM patients despite their characteristic tumor-induced immunodeficiency, and has proven to have limited efficacy in advanced MM patients. PMID- 8520516 TI - Increase of bone marrow cellularity during erythropoietin treatment in myeloma. AB - Treatment of myeloma-associated chronic anemia with recombinant human erythropoietin (rHuEPO) has been shown to be successful in the majority of patients. We have morphometrically investigated bone marrow sections from the iliac crest of 20 anemic myeloma patients prior to rHuEPO therapy. The 15 responding patients were re-examined after three months and, if possible, after 6 and 12 months of treatment. Significant differences were found between responders and nonresponders prior to therapy. Nonresponders presented with a pronounced shift to the right in their erythroid bone marrow cell compartment and partly with higher serum levels of endogenous erythropoietin. During rHuEPO therapy, responders showed increases in all subsets of erythropoiesis and in the total amount of hemopoietic tissue. Response was accompanied by a marked drop of serum ferritin levels, a rise in serum levels of transferrin receptors and the emptying of bone marrow iron stores; the World Health Organization performance status improved. Responders tended to present with less advanced disease stages and better performance status and showed significantly longer survival times. Loss of responsiveness to rHuEPO was observed in one patient during the terminal stage of the disease. In conclusion, morphometric examination of bone marrow biopsies during the course of rHuEPO therapy showed that the response achieved in hemoglobin values was clearly mirrored in equivalent increments of the erythroid bone marrow cell compartment. PMID- 8520517 TI - Current therapy of refractory multiple myeloma. AB - Induction therapy with standard regimens induces an average objective response (OR) rate (Southwest Oncology Group [SWOG] Criteria) of 40%-50% in patients with previously untreated multiple myeloma (MM) [1, 2]. The great majority of those who initially achieve remission eventually relapse, with less than 20% of patients being in ongoing remission at five years from time of initial therapy [1]. At least 30% of MM patients fail to adequately respond to induction chemotherapy [3, 4]. Patients may exhibit clinical deterioration, increasing paraprotein levels, increasing marrow suppression, refractory hypercalcemia or worsening renal failure while undergoing induction therapy. Patients who do not achieve an OR to induction therapy are sometimes described as "nonresponders." This group includes patients who are truly primarily resistant to front-line therapy, patients whose disease is in plateau phase at time of disease presentation, and patients who are slow responders to their induction therapy. The terms "refractory" or "advanced" are often applied to patients who have either primary resistant or relapsed disease. The lack of agreed terminology is a major stumbling block to data review and the logical planning of clinical studies. A classification of relapsed and resistant disease is proposed in Figure 1. Prolongation of median survival beyond one year in studies of therapy for refractory MM patients is rarely achieved [3-104]. Failure of current cytotoxic therapy has led to attempts to improve treatment by the investigation of mechanisms of cytotoxic drug resistance, the development of methods to identify drug-resistant MM cells, and attempts to either prevent or, once established, to circumvent drug resistance [105-109]. Recent data on cytotoxic and/or systemic radiation therapy will be reviewed. PMID- 8520518 TI - Intracytoplasmic sequences involved in the biological properties of low-affinity receptors for IgG expressed by murine macrophages. AB - Murine macrophages express several receptors for the Fc portion of IgG antibodies (Fc gamma R). These are high-affinity Fc gamma RI, which bind monomeric IgG2a, and low-affinity Fc gamma RII and Fc gamma RIII, which bind IgG1, IgG2a and IgG2b immune complexes. Fc gamma Ri and Fc gamma RIII are multichain receptors. They are composed of an IgG-binding alpha subunit, associated with the same FcR gamma subunit that also associates with mast cell high-affinity IgE receptors (Fc epsilon RI). Fc gamma RII are single-chain receptors. They exist as two isoforms, Fc gamma RIIb1 and Fc gamma RIIb2, differing by a 47-amino acid insertion in the intracytoplasmic domain of Fc gamma RIIb1. Using a model of stable transfectants, we analyzed the biological activities triggered by Fc gamma R and, by site directed mutagenesis, we mapped functional sequences in the intracytoplasmic domains of recombinant Fc gamma R. A single tyrosine-based activation motif (ITAM), in the intracytoplasmic domain of the FcR gamma subunit of Fc gamma RIII and Fc gamma RI, triggers cell activation, endocytosis and phagocytosis. Two distinct motifs, in the intracytoplasmic domain of Fc gamma RIIb2, trigger endocytosis and phagocytosis, respectively. The Fc gamma RIIb1-specific intracytoplasmic insertion mediates capping and down-regulates Fc gamma RII dependent internalization. A tyrosine-based inhibitory motif (ITIM), in intracytoplasmic sequences common to Fc gamma RIIb1 and Fc gamma RIIb2, was identified as down-regulating ITAM-dependent cell activation. The variety of biological properties of Fc gamma R implies that macrophage responses triggered by IgG antibodies depend on the complex interplay between different Fc gamma R having common ligands that are coexpressed by mouse macrophages. PMID- 8520519 TI - Hormonal regulation of cytosolic calcium levels in the liver. AB - Regulation of free cytosolic Ca2+ level in the liver is important because of the many Ca2(+)-dependent processes in the liver, such as respiration, gluconeogenesis, glycogenolysis, cell division, etc. Free cytosolic Ca2+ levels are maintained in the unstimulated state below 1 microM. This level is maintained by an outwardly directed Ca2(+)-ATPase in the plasma membrane, sequestration into the endoplasmic reticulum by a Ca2(+)-ATPase, binding of Ca2+ to specific Ca2(+) binding proteins, such as calmodulin, and membrane potential-driven uptake into the mitochondria. Upon stimulation by hormones which act by increasing cytosolic free Ca2+ levels, both Ca2+ influx and the release of stored Ca2+ from the endoplasmic reticulum contribute to the increases in cytosolic free Ca2+ levels. The exact mechanism(s) by which these events occur is being intensively studied and debated. Here, it is suggested that hormones activate through a second messenger 1) a ligand-gated Ca2+ channel present in the plasma membrane, and 2) a different Ca2+ channel present in the endoplasmic reticulum. As a result, cytosolic-free Ca2+ levels increase and Ca2(+)-dependent processes are activated. A role for the cytoskeleton in the activation of the ryanodine-binding channel is proposed. Future studies are needed to identify the molecular identity of the hepatic ryanodine receptor and to define the role of the cytoskeleton in signal transduction. PMID- 8520520 TI - Effect of dimethyl sulfoxide on reverse transcriptase activity. AB - At low concentrations, dimethyl sulfoxide (DMSO) stimulated the avian myeloblastosis virus reverse transcriptase activity. About 40% stimulation was obtained in the presence of 5% (v/v) DMSO, using activated DNA and polyriboadenylic acid (poly(rA)) as templates, and Mg2+ as divalent cation. A similar stimulation by DMSO was observed with Mn2+ for the poly(rA)-dependent reverse transcriptase activity. DMSO at concentrations higher than 15% inhibited the reverse transcriptase reactions, independent of the template-primers used. An exception was detected with the 2'-fluoro analog of poly(rA) as template, where an activation of 100% was found in the presence of 20% DMSO. The stimulation caused by DMSO could be due to a reduction of the apparent Km value for poly(rA) from 9.1 to 3.3 micrograms/ml. PMID- 8520521 TI - Action of immobilized xanthine oxidase on purines. AB - Xanthine oxidase was covalently immobilized on polyacrylamide gel beads, polyamide-11 and dacron. Hypoxanthine (15 ml of 200 microM), prepared in 0.1 M phosphate buffer, pH 8.0, was circulated through a column containing 1.0 g derivatized enzyme at a flow rate of 1.0 ml/min at 28 degrees C. Specific activities of 0.660, 0.072 and 0.016 Units/mg of protein were demonstrable for the polyacrylamide gel beads, dacron and polyamide-11 derivatives, respectively. The action of these water insoluble enzyme derivatives on 6-mercaptopurine (15 ml of 660 microM) was also investigated, under the same experimental conditions, showing specific activities of 0.063 Units/mg, 0.574 muUnits/mg and 0.118 muUnits/mg, respectively. The 6-mercaptopurine oxidative pathway catalyzed by immobilized xanthine oxidase on dacron stopped at the intermediate compound, 6 mercapto-8-hydroxypurine, so that no 6-thiouric acid was produced, whereas the immobilized preparations using polyacrylamide gel beads and polyamide-11 behaved like the soluble enzyme, namely, 6-thiouric acid was the final product. The behavior of dacron-xanthine oxidase compound was similar to that previously described for the derivatives obtained with carboxymethylcellulose and chitosan. The hypoxanthine oxidative pathway catalyzed by xanthine oxidase immobilized on these three supports was similar to the soluble enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520522 TI - Insulin resistance in psoriasis. AB - The oral glucose tolerance test (OGTT) and intravenous insulin tolerance test (15 min ITT) were applied to ten patients with psoriasis and to 11 control subjects. No significant differences in mean plasma glucose levels were detected between psoriatic patients and normal individuals. In contrast, serum insulin levels were significantly higher for the psoriatic patients as compared to the controls at 30, 60 and 120 min during the OGTT (P < 0.05). The glucose disappearance rate during the 15-min ITT was lower in patients with psoriasis than in controls (5.1 +/- 0.5%/min vs 7.5 +/- 0.4%/min, P < 0.05), demonstrating a state of insulin resistance. Interestingly, the reduction in serum potassium levels during the ITT was also lower in the patients than in the controls (0.6 +/- 0.06 mEq/l vs 1.06 +/- 0.07 mEq/l, P < 0.05), suggesting that the insulin resistance observed in psoriasis is not only related to glucose metabolism, but also to another important action of insulin, namely extrarenal potassium homeostasis. PMID- 8520523 TI - Hematological changes induced by Bothrops jararaca venom in dogs. AB - The mechanism of consumption coagulopathy observed in cases of human envenomation by Bothrops jararaca is well established. However, this mechanism may vary according to the animal species studied. In order to study both the clinical and laboratory aspects of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 micrograms/kg) was given intravenously. A coagulopathy similar to that observed in humans - including fibrinogen depletion, consumption of factors II, X, V and antithrombin III, and moderate thrombocytopenia - was observed. The presence of circulating activated platelets was also noted. Neutrophilic leukocytosis, lymphopenia, and monocytosis occurred at different times. Erythrocytic values remained normal in dogs treated with B. jararaca venom compared with those treated with saline alone. The erythrocyte sedimentation rate fell rapidly after venom administration and this fall was correlated logarithmically with fibrinogen concentration. Since the effects of envenomation in dogs is similar to that in humans, it was concluded that the dog can be used as a good animal model for studying human venom-induced coagulopathy. PMID- 8520525 TI - Protective effect of Saccharomyces boulardii against the cholera toxin in rats. AB - The effect of orogastric administration of Saccharomyces boulardii on the anatomopathological aspect of the jejunal villi was studied in male Fischer rats (weighing about 40 g) orogastrically infected with a culture of Vibrio cholerae. Experimental and control groups received lyophilized S. boulardii (25 mg suspended in 0.5 ml saline) or 0.5 ml saline, respectively, three times a day for 10 days by gastric intubation. On day 5 of treatment, 0.5 ml of a culture of V. cholerae containing 10(8) viable cells was inoculated by gastric intubation into both groups. Histopathological examination of the jejunal mucosa showed extensive lesions of the superficial epithelium of the villi from the control group whereas few lesions of this superficial epithelium were observed in the experimental group. These data show that the inhibition of the action of the cholera toxin on enterocytes by S. boulardii suggested by recent results in vitro can be demonstrated in vivo. PMID- 8520524 TI - Intragastric infection induced in marmosets (Callithrix jacchus) by a Brazilian hepatitis A virus (HAF-203). AB - Several species of non-human primates have been used in studies on experimental infection with hepatitis A virus (HAV). Attempts to infect a South-American marmoset (Callithrix jacchus) with a Brazilian HAV isolate (HAF-203) are described here. Four seronegative animals were inoculated intragastrically and one was sacrificed on day 11, 20, 47 and 62 after infection. One uninfected animal was included as control. Liver, small intestine, lymph node, spleen and kidney samples were collected for histological diagnosis and immunocytochemistry studies. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum enzymes and anti-HAV antibodies were monitored by a colorimetric procedure (Abbott) and an enzyme immunoassay (ELISA), respectively. Feces were collected daily for HAV antigen (HAVAg) detection by ELISA. Increased levels of HAVAg were detected in hepatocytes 11 days after infection, with a gradual decrease during the course of infection. Shedding of HAVAg in feces was observed from the late incubation to the early acute phase (20th day to 47th day after infection). The end of the incubation period was indicated by the initial increases in serum ALT and AST. Severe hepatic lesions such as piecemeal necrosis and bridging necrosis were detected during the acute phase, coinciding with the maximum transaminase levels and the appearance of anti-HAV antibodies. On the 62nd day (convalescent phase), the hepatic tissue showed evidence of regeneration and the transaminase values had returned to baselines. The serological, biochemical, antigenic and histological evidence of hepatitis A was similar to that observed in several primate models inoculated with other HAV isolates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520526 TI - Effect of HCO-3 and pH on ion transport in the posterior intestine of the freshwater-adapted teleost Anguilla anguilla. AB - The intestinal mucosa may be exposed to acidic or alcaline solutions due to liberation of digestive secretions. In several situations blood pH may also change. Consequently, the effects of HCO-3, CO2, and pH variation of medium on the ion transport across the posterior intestine of the eel (Anguilla anguilla) adapted to freshwater were studied in terms of fractional values of short-circuit current (SCC), transepithelial potential difference (TPD) and conductance (G). Immature eels weighing 100-200 g were used. The control physiological solution contained: 118.5 mM NaCl, 25.0 mM NaHCO3, 3.0 mM CaCl2.2H2O, 4.7 mM KCl, 1.0 mM MgCl2.6H2O, 5.0 mM D-glucose, 10.0 mM D-mannitol, pH 7.80, ans was gassed with 98% O2-2% CO2. Control values (N = 21) were: SCC = 51.90 +/- 2.8 microA.cm-2, TPD = 2.33 +/- 0.1 mV, G = 22.43 +/- 0.6 mS.cm-2. At constant pH, the reduction of HCO-3 concentration to 50% and 10% did not alter the values of SCC and TPD, but G increased with HCO-3 reduction to 10%. In the absence of HCO-3, SCC, TPD and G (slightly) decreased, but 1.5 mM HCO-3 still maintained the ion transport within control values, at constant pH. Comparing pH values from 6.65 to 8.61, higher values of SCC and TPD were observed at pH 7.45, but were little affected below and above this pH. There was a significant correlation between pH and SCC and TPD values; from the regression equations (1) SCC was zero at pHs below 6.62 and above 8.78 and (2) TPD was zero below 6.50 and above 8.71. PMID- 8520527 TI - Circulating immune complexes in patients with advanced tuberculosis and their association with autoantibodies and reduced CD4+ lymphocytes. AB - We investigated the presence of circulating immune complexes (CICs) in serum from tuberculosis (TB) patients with different degrees of pulmonary involvement. Patients were classified into four groups according to the extent of lung involvement: mild (N = 9), moderate (N = 12), moderate plus (N = 16), and severe cases (N = 10). A search for CICs by the 3.5% PEG precipitation test showed that the CIC values of patients with the moderate plus or severe form of pulmonary TB were significantly higher compared to healthy controls and to mild and moderate cases (P < 0.01 and P < 0.001, respectively). Further analysis demonstrated that increased CIC levels were associated with increased autoantibody production, since this abnormality was more prevalent in patients with advanced disease (P < 0.01), who also showed a significant reduction of CD4+ T lymphocytes. The immunoregulatory and pathogenetic implications of these findings are discussed. PMID- 8520528 TI - Neocortical spindling during wakefulness in the rat. AB - Neocortical spindling that frequently occurs in rats during wakefulness was studied to evaluate the hypotheses that spindle bursts are either the electrophysiological manifestation of a short-lasting sleep episode that briefly interrupts wakefulness (due to an urge to sleep) or a short decrease of the vigilance level. In order to evaluate sleep need, the latency to the onset of natural sleep, the percentual composition of the sleep-wakefulness cycles, and the durations and intervals of desynchronized sleep episodes were determined in six male Wistar rats weighing 250-350 g and having chronically implanted electrodes for frontal electrocorticogram and cervical electromyogram. These animals were selected on the basis of spindling manifestation during wakefulness. The occurrence of spindling during a period of repeated painful tail-pinching was subsequently measured to determine the vigilance level in the same animals. Two rats were also studied during forced immobilization for the same purpose. Sleep parameters were found to be normal in all rats studied, thus excluding the hypothesis that spindling in wakefulness is a manifestation of a high sleep need. Spindling also occurred in both situations requiring a high level of vigilance (frequent tail-pinching and forced immobilization). Natural sleep cycles never started with this type of spindling, which is not related to the typical synchronization patterns of synchronized sleep. The frequency of the potentials that make up spindles in wakefulness were systematically 1 to 2 Hz lower than those of synchronized sleep in all animals studied. The possibility that spindling during wakefulness may be associated to brief episodes of distraction is discussed. PMID- 8520529 TI - Effect of age and magnesium administration on the performance of SHR in the elevated plus-maze. AB - It is currently accepted that young spontaneously hypertensive rats (SHR) have lower pressure levels than adult SHR in which the hypertension is well established, reaching the highest plateau at about 24 weeks, and that treatment with magnesium initiated during intrauterine life postpones the onset of cardiovascular alterations in SHR to about 90 days. These animals also show many behavioral alterations. The anxiety of SHR was measured in the elevated plus maze, considering the age of the animals and previous ingestion of food supplemented with 1% magnesium oxide. Both young (1.5-2 months) and adult (5-6 months) SHR showed higher mean ( +/- SEM) percent of entries (48 +/- 3 and 51 +/- 3, respectively) and a longer mean ( +/- SEM) percent of time spent (43 +/- 5 and 55 +/- 5, respectively) in the open arms when compared to the mean ( +/- SEM) percent of entries and time spent in the open arms of young (35 +/- 3 and 20 +/- 4, respectively) and adult (36 +/- 7 and 17 +/- 5, respectively) normotensive Wistar rats. Treatment with magnesium oxide did not alter the performance of SHR in the elevated plus-maze. SHR showed an anxiolytic-like behavior which was neither influenced by age nor by antihypertensive treatment. PMID- 8520530 TI - Effect of d-fenfluramine on cortical spreading depression in rats. AB - We investigated the effect of a single ip injection of d-fenfluramine (d-fen; 5 10 mg/kg), a serotonin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2% KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 +/- 0.63 vs 2.66 +/- 0.51 mm/min; N = 17, P < 0.001), at t = 40 min (3.32 +/- 0.58 vs 2.53 +/- 0.52 mm/min; N = 14, P < 0.001), at t = 60 min (3.68 +/- 0.63 vs 2.92 +/- 0.72 mm/min; N = 11, P < 0.001) and at t = 80 min (3.57 +/- 0.61 vs 3.03 +/- 0.83 mm/min; N = 12, P < 0.05) but not at t = 100 min (3.47 +/- 0.72 vs 3.31 +/- 0.88 mm/min; N = 12) nor at t = 120 min (3.44 +/- 0.67 vs 3.37 +/- 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40%) performed after d-fen in 8 rats (47%), SD velocity could not be evaluated since the phenomenon, after reaching the recording electrode nearest the stimulating point, interrupted the propagation before the second recording electrode was reached.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520531 TI - Intracerebroventricular administration of cholecystokinin reduces stereotypy in dopamine-supersensitive rats. AB - Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 microliters) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. Experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK 8 (HCCK, N = 11) icv and long-term saline-treated rats that received CCK-8 (SCCK, N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 +/- 1.7 vs 31 +/- 1.6; P < 0.05) and CCK-8 significantly reduced stereotyped behavior in supersensitive rats (42 +/- 1.7 vs 37 +/- 1.5; P < 0.05). These results show that CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8. PMID- 8520532 TI - Embryotoxic effects of misoprostol in the mouse. AB - Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively misused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP (20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain (day 10-11: control, 1.3 +/- 0.3 g; MSP 20 mg/kg, -0.9 +/- 0.9 g; MSP 30 mg/kg, -1.7 +/- 0.6 g) was the only sign of maternal toxicity noted in both groups of mice treated with misoprostol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520533 TI - Decrease in the ratio of high- to low-affinity isozymes of (Na+ +K+)-ATPase during the development of rat cardiac ventricles. AB - The ratio of (Na+ +K+)-ATPase (EC 3.6.1.3.)isoforms with high and low affinity for cardiac glycosides was studied in heart preparations from neonatal, 3-month and 6-month old Wistar rats. Biphasic ouabain inhibition curves of (Na+ +K+) ATPase activity indicated that the relative contribution of the high-affinity process decreased from 34% at 9 days to 23% at 3 months and to 10% at 6 months. Scatchard plots for [3H]ouabain binding were curvilinear and indicated that the relative contribution of the high-affinity sites (Kd = 0.1-0.25 microM) decreased by about one-half between 3 months (19-24%, N = 2) and 6 months (9-11%, N = 2). PMID- 8520534 TI - The effect of adipose cell size on the measurement of GLUT 4 in white adipose tissue of obese mice. AB - Glucose transporter (GLUT 4) was assessed in subcellular membrane fractions of white adipose tissue (WAT) from obese insulin-resistant aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice. Obesity was demonstrated by increased body weight and/or Lee index, as well as by the heavier WAT and brown adipose tissue in relation to similar weights of gastrocnemius and heart. In vivo insulin resistance in obese animals was suggested by moderate hyperglycemia and severe hyperinsulinemia. Morphological analyses of adipose cells showed a > 10-fold increase in cell volume of obese mice. Subcellular fractionation indicated a reduced (P < 0.01) protein membrane content in the fat-free extract (FFE) from obese mice. However, the specific activity of 5'nucleotidase, a plasma membrane (PM) marker, in FFE and PM did not differ among groups. In addition, the total PM enzyme activity per unit of cell surface area was also unchanged. The GLUT 4 content, assessed by Western blotting and expressed per microgram membrane protein, was reduced by approximately 50% (P < 0.01) in all membrane fractions from obese animals. However, the total FFE GLUT 4 content per cell was increased (P < 0.01), from 23.5 +/- 1.8 in controls to 62.4 +/- 7.6 and 47.4 +/- 5.9 cpm cell-1 10(-3) in AuTG and MSG, respectively, but the total PM GLUT 4 content per unit of cell surface area was highly reduced (P < 0.01), from 165.1 +/- 16.7 in controls to 53.8 +/- 10.9 and 32.0 +/- 5.3 cpm microns-2 10(-9) in AuTG and MSG, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520535 TI - Mechanisms underlying the genesis of post-extrasystolic potentiation in rat cardiac muscle. AB - Changes of contractility resulting from changes in stimulation pattern (post extrasystolic potentiation - PESP) were investigated in right ventricular papillary muscles from female albino rats (EPM strain, 160-200 g). The preparations were superfused with bicarbonate buffered solution at 24 +/- 0.5 degrees C, and stimulated at 0.5 Hz. Maintained paired stimulation was performed at several coupling intervals (360, 500, 660, 770 and 920 ms) with normal Krebs for 30 s. After treatment with ryanodine (1 microM), used as an inhibitor of the release of sarcoplasmic reticulum Ca2+ activity, the same protocol was repeated in the presence of normal Krebs, low Na+ (80 mM, LiCl used as substitute) and low K+ concentrations to change the level of activity of the Na+/Ca2+ exchange mechanism. With normal Krebs, paired pulse stimulation produced a maintained potentiation of the post-extrasystolic beat and an extrasystole with a reduced force generation when compared to the control steady-state contraction. As the interval between the extrasystole and the normal beat was increased the potentiation of the post-extrasystolic beat was reduced and the force of the extrasystole was increased. Ryanodine treatment reduced the force of contraction and increased its duration, and the pattern of the PESP phenomenon was altered. Both the post-extrasystolic and the extrasystolic beats were potentiated compared to the steady-state contraction obtained under ryanodine treatment. The extrasystole displayed a greater potentiation than the post-extrasystolic beat. As the interval between them increased the amplitude of the extrasystolic beat was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520536 TI - Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats. Evidence for a somatotopic organization. AB - Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61% of the times and an increase of blood pressure and heart rate in approximately 80% of the stimulations. Stimulation of a hindlimb provoked an increase of blood flow in the same limb in about 80% of the stimulations, due to active vasodilation. Contralateral stimulation provoked a smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs. The vasodilation was not due to activation of sympathetic cholinergic vasodilator neurons inasmuch as the blood flow responses were not affected by cholinergic blockade with atropine. In spinal animals, stimulation of any limb provoked small increases of blood pressure, extremely low degrees of tachycardia and an increase of hindlimb blood flow, with active vasodilation. Neuromuscular paralysis, however, abolished the adjustments of blood flow in the hindlimbs, indicating that metabolites and/or sensory information caused by muscle contraction induced them. In intact cats anesthetized with sodium pentobarbiturate, blood pressure and heart rate increased under noxious stimulation, although less than in the decerebrate animals. Nearly 40% of the stimulations provoked hypotension rather than hypertension. Blood flow increased due to stimulation of any limb but, as in the decerebrate preparation, there was active vasodilation in the ipsilateral hindlimb and vasoconstriction in the contralateral one. PMID- 8520537 TI - The art of parasite survival. AB - Parasites develop and survive in an environment which is often hostile to them. When facing aggressive conditions parasites are able to use various and complex strategies. Echinococcus granulosus, Toxocara canis, Pneumocystis carinii, Entamoeba or Toxoplasma gondii are able to seclude from the environment when stressed by surrounding (immunologic or non-immunologic) aggressive factors. Specific antigens which exert a functional activity during a short period of time appear to be concealed from the immune attack at this crucial moment. This is the case for rhoptry or dense granule antigens of Plasmodium or Toxoplasma sporozoa involved in the formation of the parasitophorous vacuole which are released in a space perfectly isolated from the outside and therefore from antibodies. Some parasites like Schistosoma mansoni or Trypanosoma brucei reveal an amazing opportunistic behavior when they use cytokines of host origin induced by the infectious process for their own development. Leishmania, Toxoplasma and Trypanosoma cruzi are able to invade immunologically competent macrophages and to avoid the triggering of killing mechanisms of these cells. Parasites also take advantage of the genetic restriction of the immune response and it has been observed for Plasmodia that some high molecular weight antigens are unable to induce an immune response in particular strains of mice. Parasite receptors involved in the invasion of host cells by parasites can function in the presence of antibodies which can explain the failure of vaccination attempts targeting this type of molecules. Among the mechanisms developed by parasites to resist to drugs it appears that transmembrane transporters described in many protozoa or helminth parasites could play a role. Moreover, the description of parasite specific enzymes able to protect them against the damaging effects of oxygen radicals suggests that parasites are potentially able to develop a resistance phenomenon against drugs acting via an oxidative burst. PMID- 8520539 TI - Clearance of a chylomicron-like emulsion from plasma is delayed in patients with coronary artery disease. AB - To determine whether the metabolism of chylomicrons and their remnants is related to atherogenesis, a triglyceride-rich emulsion known to mimic chylomicron behavior in plasma and labeled with 1-14C-cholesteryl oleate was injected intravenously into 11 normolipidemic patients (triglycerides: 133 +/- 60 mg/dl; total cholesterol: 207 +/- 20 mg/dl; LDL: 143 +/- 20 mg/dl; VLDL: 27 +/- 13 mg/dl; and HDL cholesterol: 41 +/- 11 mg/dl; apo AI: 1.27 +/- 0.54 g/l and apo B: 1.42 +/- 0.31 g/l) with atherosclerotic coronary artery disease and into 11 control subjects (triglycerides: 109 +/- 32 mg/dl; total cholesterol: 190 +/- 38 mg/dl; LDL: 125 +/- 29 mg/dl; VLDL: 22 +/- 6 mg/ dl; and HDL cholesterol: 44 +/- 9 mg/dl; apo AI: 1.09 +/- 0.28 g/l and apo B: 1.09 +/- 0.28 g/l) without the disease. The emulsion (69% triolein, 23% lecithin, 6% cholesteryl oleate and 2% cholesterol) was injected intravenously at approximately 9:00 a.m., after a 12-h fast. The clearance of the emulsion label from plasma, expressed as fractional clearance rate (FCR), was lower in coronary artery disease compared to controls (0.019 +/- 0.005/min vs 0.036 +/- 0.018/min, respectively, P < 0.05). These results indicate that the rate of removal of chylomicron remnants is slower in patients with coronary artery disease. PMID- 8520538 TI - Cardiac intercellular communication: consequences of connexin distribution and diversity. AB - Gap junctions contain channels which allow the exchange of ions and small molecules between adjacent cells. In the heart, these channels are crucial for normal intercellular current flow and the propagation of action potentials throughout the myocardium. Molecular cloning studies have demonstrated that these channels are formed by members of a family of related proteins called connexins each containing conserved and unique regions. There are several consequences of this multiplicity of connexins. Multiple connexins are expressed in differing, but sometimes overlapping, distributions within cardiovascular and other tissues. Connexin40, connexin43, and connexin45 are all found in cardiac myocytes, but their abundance differs in specialized cardiac regions with disparate conductive properties. Individual connexins form channels with differing voltage-dependence, conductance, and permeability properties, as demonstrated by functional expression of the cloned sequences. Connexins differ in their modification by phosphorylation, which may contribute to physiological regulation of intercellular communication. Expression of multiple connexins may lead to the formation of multiple channel types in a single tissue or cell and potentially allows mixing to form heterotypic and/or heteromeric channels. Thus, multiple connexins may contribute to the differences in intercellular resistance in cardiac regions with differing conductive properties and possibly may allow differences in the signalling molecules that pass between cells. PMID- 8520540 TI - Nocturnal urinary growth hormone excretion as a criterion for growth hormone deficiency. AB - Nocturnal urinary growth hormone (U-hGH) levels measured by a sensitive immunoenzymometric assay were compared with hGH levels in serum before and after a clonidine test in healthy children and in children with short stature to determine whether U-hGH measurement is useful for the screening of hGH deficiency. The study was carried out on 19 healthy children (10 prepubertal and 9 pubertal subjects) and on 20 children with short stature, 10 with growth hormone deficiency (hGHD) and 10 with constitutional growth retardation. The diagnosis of hGHD was based on a blunted response to two provocative hGH tests in the appropriate clinical setting. Overnight urinary hGH secretion (mean of 3 collections) was measured by an immunoenzymometric assay. The best discrimination was obtained when the results were expressed as ng/h. Only one individual in the prepubertal group (U-hGH, 0.05 ng/h) and one patient in the growth retardation group (U-hGH, 0.08 ng/h) had a urinary hGH value below the highest value (0.17 ng/h) observed in the growth hormone deficiency group. The coefficient of correlation between urinary hGH in ng/h and post-clonidine peak was 0.50 (P = 0.0015), between urinary hGH in ng/l and post-clonidine peak was 0.48 (P = 0.0025), between urinary hGH in ng/l per hour and post-clonidine peak was 0.47 (P = 0.0027). The highest specificity (0.93), sensitivity (0.90), false negative rate (0.96) and false positive rate (0.82) were obtained when U-hGH was expressed as ng/h per night. Measurement of urinary nocturnal hGH excretion is a useful, simple, noninvasive method for the diagnosis of hGH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8520541 TI - Lipoprotein (a) in subjects with or without coronary artery disease: relation to clinical history and risk factors. AB - Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein resembling low-density lipoprotein (LDL) but with an additional apoprotein (apo), apo(a). To determine whether plasma Lp(a) levels can influence the clinical presentation and extent of coronary artery disease (CAD), Lp(a), plasma lipids and apolipoproteins were determined in 203 Caucasian subjects with CAD and in 66 subjects without CAD, all confirmed by cinecoronariography. CAD patients were divided into groups according to their clinical history. The extent of the disease was evaluated by a scoring system. Lp(a) was elevated in CAD patients compared to subjects without CAD. However, there was no difference between patients that had myocardial infarction as the first manifestation of the disease and those who had only angina pectoris for at least two years. Plasma Lp(a) levels were correlated with extent of the disease. Among patients with CAD, Lp(a) was higher in females. Lp(a) was also studied separately in 29 Black subjects, 12 without CAD and 17 with CAD. In Black subjects, Lp(a) was higher than in Caucasians but there was no difference between subjects with and without CAD. Among the other risk factors studied, only plasma apo B levels and smoking were correlated with CAD. PMID- 8520542 TI - Placental bed lesions and infant birth weight in hypertensive pregnant women. AB - Sixty pregnant women with systemic arterial hypertension, whose pregnancies were interrupted by cesarean section at the Maternity Ward of Hospital de Clinicas de Porto Alegre between May 1989 and October 1990, were examined. Specimens of the placental bed were collected by biopsy and the presence of acute atheromatosis and/or fibrinoid necrosis was investigated. The patients were divided into two groups according to the presence or absence of vascular lesions. The biopsy findings of the placental bed were compared with adequate weight at birth related to gestational age, and to the following clinical parameters of the mother: arterial blood pressure, serum creatinine, serum uric acid and proteinuria. Twenty-seven (45%) patients presented vascular lesions in the placental bed compatible with acute atheromatosis and/or fibrinoid necrosis. The presence of vascular changes in the placental bed correlated significantly to diminished weight of the newborn, in terms of the mean weight and in terms of small-for gestational-age infants, non-nephrotic proteinuria ( > or = 300 mg/24 h) and increased levels of uric acid ( > 5.5 mg/dl). PMID- 8520543 TI - Clonal heterogeneity in murine liver myofibroblasts. AB - GR primary cells cultures were isolated from hepatic granulomas induced in C3H mice livers by Schistosoma mansoni infection; the GRX continuous cell line was derived from GR cells after long-term culture and a progressive drift towards a rapidly proliferating cell population. These cells were analyzed and compared in terms of their clonal heterogeneity. Clones were classified on the basis of cell substrate, cell-cell adhesion (growth morphology of the clone) and fat droplet accumulation. GR cells were composed of two slow-growing clone types, while GRX cells gave rise to clones with several phenotypes, including the two found in the GR cells. The overall proportion of different clones in the GRX cell population was stable in long-term cultures, as well as after recloning of the highly proliferating, but not the slowly proliferating, clones. We propose that the slow growing clones are maintained in the overall population by continuous contribution of new slow-growing cells from the rapidly growing ones. The slow growing clones may represent the basal population of liver connective tissue cells that can be mobilized into injured tissues and that are involved in tissue repair. The highly proliferating clones with a broad capacity of phenotype expression that arise after long-term growth stimulation of the local cell population may represent the hypertrophic connective tissue cells, such as those observed in progressive fibrotic reactions associated with chronic liver tissue inflammation. PMID- 8520544 TI - Effects of protein malnutrition on glucose tolerance in rats with alloxan-induced diabetes. AB - Protein-calorie malnutrition produces glucose intolerance and reduced insulin release in response to glucose. Rats adapted to low- or high-protein diets show an increased resistance to the diabetogenic action of a single dose of streptozotocin or alloxan. To determine the effects of dietary protein level on pancreatic function, we measured serum glucose levels under basal conditions and during the oral glucose tolerance test (GTT) performed before and after a single dose of alloxan administered to rats fed a 25% or a 6% protein diet for a period of 8 weeks. The incidence of mild hyperglycemia (serum glucose > 250 mg/dl) was greater among the rats fed the 25% protein diet (81%) than among those fed the 6% protein diet (42%). During the GTT performed before alloxan administration the serum glucose levels of the rats fed the 6% protein diet were not found to be significantly different from those of rats fed the 25% protein diet. During the GTT performed after alloxan injection all rats showed intolerance to the substrate (serum glucose > 160 mg/dl 120 min after glucose administration) regardless of whether basal serum glucose was normal or high. In summary, alloxan was less effective in producing basal hyperglycemia in the rats fed the 6% protein diet than in those fed the 25% protein diet but caused glucose intolerance during the oral GTT in both groups. Thus, it seems that feeding a 6% protein diet to rats offers only partial protection against the toxic effects of alloxan. PMID- 8520545 TI - Reduction of pancreatic enzyme content and mortality in experimental acute pancreatitis in rats. AB - A previous report has shown that undernutrition reduces the mortality of acute experimental pancreatitis probably by decreasing pancreatic enzyme content. Cerulein in physiological doses reduces the enzyme content of the pancreas without any harmful effect on the organ. The aim of the present study was to asses the effect of acute reduction of pancreatic enzyme content on the outcome of acute pancreatitis. Two groups of male Wistar rats weighing 230-250 g were studied: group I, 12-h fasted animals, and group II, ad libitum-fed animals who received cerulein at the inframaximal dose (0.2 microgram kg-1 h-1) for 2 h. Cerulein administration resulted in the reduction of the pancreatic contents of chymotrypsinogen (71%), trypsinogen (55%), proelastase (60%), amylase (62%) and cathepsin B (45%) (P < 0.05). However, no significant reduction in pancreatic phospholipase content was observed. Acute pancreatitis was induced in group I after 12-h fasting and in group II at the end of cerulein infusion by retrograde injection o 0.5 ml of 2.5% Na+ taurocholate into the pancreatic duct. Ascites volume and the degree of histologically observed lesions were similar in both groups, but 72-h mortality was 56% in the control group (10/ 18) and 23% (5/22) in the cerulein group (P < 0.05). We speculate that the reduction of pancreatic enzyme content may exert its beneficial effect in acute pancreatitis by decreasing the quantity of pancreatic enzymes reaching the circulation and consequently their pathogenic effects. PMID- 8520546 TI - Increased clearance of Candida albicans from the peritoneal cavity of mice pretreated with concanavalin A or jacalin. AB - We have studied the role of polymorphonuclear leukocytes and macrophages in the clearance of Candida albicans from the peritoneal cavity of Swiss mice after treatment with jacalin or concanavalin A (Con-A). Mice (25-30 g, N = 7 per group) received jacalin or Con-A (500 micrograms/0.5 ml PBS) intraperitoneally 96 h before intraperitoneal inoculation of 5 x 10(7) yeast cells. The clearance of Candida from the peritoneal cavity was complete 24 h after inoculation for animals pretreated with jacalin and 48 h after inoculation for animals pretreated with Con-A, whereas a reduction to 4 x 10(4) yeast cells/cavity occurred in control animals 48 h after inoculation. Pretreatment with jacalin or Con-A reduced the recovery of C. albicans from spleen, kidney and liver 10- to 80-fold compared to control animals. Pretreatment with the lectins increased the number of phagocytic cells in the peritoneal exudate 5- to 10-fold and their candidacidal activity was increased 6-fold compared to controls. These data explain the increased rate of clearance and reduced yeast dissemination to the viscera of lectin treated mice. PMID- 8520547 TI - Daily variation of serum cortisol, 17-hydroxyprogesterone and five androgens in healthy women. AB - Serum cortisol, 17-hydroxyprogesterone and five androgens (androstenedione, 11 hydroxyandrostenedione, dehydroepiandrosterone and its sulphate, and testosterone) were measured by radioimmunoassay at 8:00, 16:00, 20:00 and 24:00 h and again at 8:00 h on the next day in eight healthy female subjects aged 16-40 years in the midfollicular phase of the menstrual cycle. Regression analysis revealed a significant (alpha = 0.05) circadian periodicity, with estimated peaks between 8:00 a.m. (testosterone) and 2:00 p.m. (dehydroepiandrosterone sulphate), and with estimated amplitudes between 76% (11-hydroxyandrostenedione) and 33% (17 hydroxyprogesterone, testosterone and dehydroepiandrosterone sulphate) of the rhythm adjusted mean. The inferential statistical approach illustrated here should contribute significantly to the diagnostic elucidation of adrenocortical disorders.